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Oswald T, Malomo S, Alway T, Hadjivassilev S, Coombs S, Ellery S, Lee J, Phillips C, Philips B, James R, Hildick-Smith D, Parish V, Liu A. Guideline-Directed Medical Therapy in Sepsis Survivors with Left Ventricular Systolic Dysfunction: An Observational Study. J Clin Med 2025; 14:3253. [PMID: 40364284 PMCID: PMC12072734 DOI: 10.3390/jcm14093253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2025] [Revised: 04/18/2025] [Accepted: 05/03/2025] [Indexed: 05/15/2025] Open
Abstract
Background: Sepsis survivors can develop left ventricular systolic dysfunction (LVSD) and heart failure. These patients are often treated with guideline-directed medical therapy (GDMT) known to be effective in patients with non-sepsis-related heart failure. This study sought to assess the use of GDMT on sepsis survivors with LVSD. Methods: Sepsis survivors with suspected myocardial injury and/or heart failure diagnosed with LVSD in a UK cardiac centre were retrospectively studied. Clinical and transthoracic echocardiography (TTE) data were recorded and analysed. Results: Of the 25 sepsis survivors (age 56 ± 11 years; 52% males), 11 (44%) had LVSD (LVEF < 50%). LV end-diastolic internal diameter (LVIDd) was similar between patients with vs. without LVSD (5.2 ± 0.8 cm vs. 4.7 ± 0.8 cm; p = 0.214). Patients with LVSD had significantly greater LV end-systolic internal diameter (LVIDs) than those without LVSD (4.0 ± 1.2 cm vs. 2.8 ± 0.6 cm; p = 0.027). Tricuspid annular plane systolic excursion (TAPSE) was similar between the two groups (2.1 ± 0.5 cm vs. 2.2 ± 0.6 cm; p = 0.910). Of the 11 patients with LVSD, nine patients underwent repeat TTE scans after 6 months [IQR 3-9], most of whom were taking GDMT. The majority (8/9) of these patients demonstrated LV systolic functional recovery (>5% LVEF increase; mean LVEF improvement 16 ± 11%) after GDMT. Reductions were seen in LVIDd (5.3 ± 0.8 cm to 5.0 ± 0.7 cm) and LVIDs (4.1 ± 1.2 cm to 3.7 ± 0.8 cm) after GDMT, though these changes did not reach statistical significance (both p > 0.05). Conclusions: GDMT appears beneficial in sepsis survivors with LV dysfunction. This finding should be validated on a larger and multi-centre basis to further affirm the value of medical therapy in post-sepsis heart failure.
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Affiliation(s)
- Thomas Oswald
- Sussex Cardiac Centre, Royal Sussex County Hospital, Brighton BN2 5BE, UK; (T.O.); (S.M.); (T.A.); (S.H.); (S.C.); (S.E.); (J.L.); (R.J.); (D.H.-S.); (V.P.)
| | - Samuel Malomo
- Sussex Cardiac Centre, Royal Sussex County Hospital, Brighton BN2 5BE, UK; (T.O.); (S.M.); (T.A.); (S.H.); (S.C.); (S.E.); (J.L.); (R.J.); (D.H.-S.); (V.P.)
| | - Thomas Alway
- Sussex Cardiac Centre, Royal Sussex County Hospital, Brighton BN2 5BE, UK; (T.O.); (S.M.); (T.A.); (S.H.); (S.C.); (S.E.); (J.L.); (R.J.); (D.H.-S.); (V.P.)
| | - Stanislav Hadjivassilev
- Sussex Cardiac Centre, Royal Sussex County Hospital, Brighton BN2 5BE, UK; (T.O.); (S.M.); (T.A.); (S.H.); (S.C.); (S.E.); (J.L.); (R.J.); (D.H.-S.); (V.P.)
| | - Steven Coombs
- Sussex Cardiac Centre, Royal Sussex County Hospital, Brighton BN2 5BE, UK; (T.O.); (S.M.); (T.A.); (S.H.); (S.C.); (S.E.); (J.L.); (R.J.); (D.H.-S.); (V.P.)
| | - Susan Ellery
- Sussex Cardiac Centre, Royal Sussex County Hospital, Brighton BN2 5BE, UK; (T.O.); (S.M.); (T.A.); (S.H.); (S.C.); (S.E.); (J.L.); (R.J.); (D.H.-S.); (V.P.)
| | - Joon Lee
- Sussex Cardiac Centre, Royal Sussex County Hospital, Brighton BN2 5BE, UK; (T.O.); (S.M.); (T.A.); (S.H.); (S.C.); (S.E.); (J.L.); (R.J.); (D.H.-S.); (V.P.)
| | - Claire Phillips
- Intensive Care Unit, Royal Sussex County Hospital, Brighton BN2 5BE, UK; (C.P.); (B.P.)
| | - Barbara Philips
- Intensive Care Unit, Royal Sussex County Hospital, Brighton BN2 5BE, UK; (C.P.); (B.P.)
- Brighton and Sussex Medical School, Brighton BN1 9PX, UK
| | - Rachael James
- Sussex Cardiac Centre, Royal Sussex County Hospital, Brighton BN2 5BE, UK; (T.O.); (S.M.); (T.A.); (S.H.); (S.C.); (S.E.); (J.L.); (R.J.); (D.H.-S.); (V.P.)
| | - David Hildick-Smith
- Sussex Cardiac Centre, Royal Sussex County Hospital, Brighton BN2 5BE, UK; (T.O.); (S.M.); (T.A.); (S.H.); (S.C.); (S.E.); (J.L.); (R.J.); (D.H.-S.); (V.P.)
| | - Victoria Parish
- Sussex Cardiac Centre, Royal Sussex County Hospital, Brighton BN2 5BE, UK; (T.O.); (S.M.); (T.A.); (S.H.); (S.C.); (S.E.); (J.L.); (R.J.); (D.H.-S.); (V.P.)
| | - Alexander Liu
- Sussex Cardiac Centre, Royal Sussex County Hospital, Brighton BN2 5BE, UK; (T.O.); (S.M.); (T.A.); (S.H.); (S.C.); (S.E.); (J.L.); (R.J.); (D.H.-S.); (V.P.)
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Malomo S, Oswald T, Stephenson E, Yip A, Alway T, Hadjivassilev S, Coombs S, Ellery S, Lee J, James R, Phillips C, Philips B, Hildick-Smith D, Parish V, Liu A. Characterisation of Post-Sepsis Cardiomyopathy Using Cardiovascular Magnetic Resonance. Diagnostics (Basel) 2025; 15:997. [PMID: 40310393 PMCID: PMC12025626 DOI: 10.3390/diagnostics15080997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2025] [Revised: 03/26/2025] [Accepted: 04/04/2025] [Indexed: 05/02/2025] Open
Abstract
Background: Post-sepsis cardiomyopathy is associated with an increased risk of adverse cardiovascular outcomes. It remains poorly understood, which limits therapeutic development. This study characterised post-sepsis cardiomyopathy using cardiovascular magnetic resonance (CMR) imaging. Methods: Patients admitted with acute sepsis and suspected cardiac injury or heart failure who subsequently (47 days [IQR: 22-122]) underwent CMR at a UK tertiary cardiac centre were included. Age- and gender-matched controls (n = 16) were also included. Subjects underwent CMR at 1.5 Tesla with cines, native T1- and T2-mapping, and late gadolinium enhancement (LGE) imaging. Results: Of the 22 post-sepsis patients (age 50 ± 13 years; 64% males), 13 patients (59%) had left ventricular (LV) dilatation. Patients had significantly elevated left ventricular (LV) end-diastolic and end-systolic volume indices compared to controls (p = 0.011 and p = 0.013, respectively). Eleven patients (50%) had LV systolic dysfunction (ejection fraction < 50%), most of whom (8/11) had non-ischaemic patterns of LGE (n = 7 mid-wall; n = 1 mid-wall/patchy). In the eleven patients with preserved LV systolic function (ejection fraction ≥ 50%), three patients (27%) had significant LGE (n = 1 mid-wall; n = 1 subepicardial/mid-wall; n = 1 patchy). Compared to controls, patients had elevated septal native myocardial T1 values (p < 0.001) but similar septal native myocardial T2 values (p = 0.090), suggesting the presence of myocardial fibrosis without significant oedema. Conclusions: Post-sepsis cardiomyopathy is characterised by LV dilatation, systolic dysfunction, and myocardial fibrosis in a non-ischaemic distribution. Significant myocardial oedema is not prominent several weeks post-recovery. Further work is needed to test these findings on a multi-centre basis and to develop novel therapies for post-sepsis cardiomyopathy.
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Affiliation(s)
- Samuel Malomo
- Sussex Cardiac Centre, Royal Sussex County Hospital, Brighton BN2 5BE, UK; (S.M.); (T.O.); (E.S.); (A.Y.); (T.A.); (S.H.); (S.C.); (S.E.); (J.L.); (R.J.); (D.H.-S.); (V.P.)
| | - Thomas Oswald
- Sussex Cardiac Centre, Royal Sussex County Hospital, Brighton BN2 5BE, UK; (S.M.); (T.O.); (E.S.); (A.Y.); (T.A.); (S.H.); (S.C.); (S.E.); (J.L.); (R.J.); (D.H.-S.); (V.P.)
| | - Edward Stephenson
- Sussex Cardiac Centre, Royal Sussex County Hospital, Brighton BN2 5BE, UK; (S.M.); (T.O.); (E.S.); (A.Y.); (T.A.); (S.H.); (S.C.); (S.E.); (J.L.); (R.J.); (D.H.-S.); (V.P.)
| | - Anthony Yip
- Sussex Cardiac Centre, Royal Sussex County Hospital, Brighton BN2 5BE, UK; (S.M.); (T.O.); (E.S.); (A.Y.); (T.A.); (S.H.); (S.C.); (S.E.); (J.L.); (R.J.); (D.H.-S.); (V.P.)
| | - Thomas Alway
- Sussex Cardiac Centre, Royal Sussex County Hospital, Brighton BN2 5BE, UK; (S.M.); (T.O.); (E.S.); (A.Y.); (T.A.); (S.H.); (S.C.); (S.E.); (J.L.); (R.J.); (D.H.-S.); (V.P.)
| | - Stanislav Hadjivassilev
- Sussex Cardiac Centre, Royal Sussex County Hospital, Brighton BN2 5BE, UK; (S.M.); (T.O.); (E.S.); (A.Y.); (T.A.); (S.H.); (S.C.); (S.E.); (J.L.); (R.J.); (D.H.-S.); (V.P.)
| | - Steven Coombs
- Sussex Cardiac Centre, Royal Sussex County Hospital, Brighton BN2 5BE, UK; (S.M.); (T.O.); (E.S.); (A.Y.); (T.A.); (S.H.); (S.C.); (S.E.); (J.L.); (R.J.); (D.H.-S.); (V.P.)
| | - Susan Ellery
- Sussex Cardiac Centre, Royal Sussex County Hospital, Brighton BN2 5BE, UK; (S.M.); (T.O.); (E.S.); (A.Y.); (T.A.); (S.H.); (S.C.); (S.E.); (J.L.); (R.J.); (D.H.-S.); (V.P.)
| | - Joon Lee
- Sussex Cardiac Centre, Royal Sussex County Hospital, Brighton BN2 5BE, UK; (S.M.); (T.O.); (E.S.); (A.Y.); (T.A.); (S.H.); (S.C.); (S.E.); (J.L.); (R.J.); (D.H.-S.); (V.P.)
| | - Rachael James
- Sussex Cardiac Centre, Royal Sussex County Hospital, Brighton BN2 5BE, UK; (S.M.); (T.O.); (E.S.); (A.Y.); (T.A.); (S.H.); (S.C.); (S.E.); (J.L.); (R.J.); (D.H.-S.); (V.P.)
| | - Claire Phillips
- Intensive Care Unit, Royal Sussex County Hospital, Brighton BN2 5BE, UK; (C.P.); (B.P.)
| | - Barbara Philips
- Intensive Care Unit, Royal Sussex County Hospital, Brighton BN2 5BE, UK; (C.P.); (B.P.)
- Brighton and Sussex Medical School, Brighton BN1 9PX, UK
| | - David Hildick-Smith
- Sussex Cardiac Centre, Royal Sussex County Hospital, Brighton BN2 5BE, UK; (S.M.); (T.O.); (E.S.); (A.Y.); (T.A.); (S.H.); (S.C.); (S.E.); (J.L.); (R.J.); (D.H.-S.); (V.P.)
| | - Victoria Parish
- Sussex Cardiac Centre, Royal Sussex County Hospital, Brighton BN2 5BE, UK; (S.M.); (T.O.); (E.S.); (A.Y.); (T.A.); (S.H.); (S.C.); (S.E.); (J.L.); (R.J.); (D.H.-S.); (V.P.)
| | - Alexander Liu
- Sussex Cardiac Centre, Royal Sussex County Hospital, Brighton BN2 5BE, UK; (S.M.); (T.O.); (E.S.); (A.Y.); (T.A.); (S.H.); (S.C.); (S.E.); (J.L.); (R.J.); (D.H.-S.); (V.P.)
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Michaud K, Basso C, de Boer HH, Fracasso T, de Gaspari M, Giordano C, Li X, Lucena J, Molina P, Parsons S, Sheppard MN, van der Wal AC. Ischemic and non-ischemic myocardial injuries at autopsy- an overview for forensic pathologists. Int J Legal Med 2025:10.1007/s00414-025-03479-1. [PMID: 40172635 DOI: 10.1007/s00414-025-03479-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Accepted: 03/18/2025] [Indexed: 04/04/2025]
Abstract
Cardiovascular diseases are major causes of morbidity and death worldwide, and most cardiac deaths are related to ischemic injury of the myocardium (myocardial infarction). As underlined in the current clinical definition and classification of myocardial infarctions, not all myocardial injuries are due to ischemia: irreversible injury, ending in necrosis, can be induced also by various other factors, such as infections, immune disorders, physical and chemical agents, and trauma. This is supported by clinical studies showing that elevated serum levels of cardiac troponins, as a measure of myocardial damage, are also a common finding in the non-ischemic types of myocardial injury. Forensic pathologists confronted with autopsy findings suggestive of myocardial injury should therefore realize that both ischemic and non-ischemic forms of myocardial death can be observed, and not only in natural but also non-natural deaths (intoxications, asphyxia, traumatic and iatrogenic deaths, and others). Distinguishing these different types of injuries and underlying diseases or circumstances of death is critical, not only to determine the cause and mechanism of death, but also to help investigate often challenging medico-legal scenarios. This article reviews the broad spectrum of ischemic and non-ischemic myocardial injuries in natural and violent deaths. From this perspective we propose a diagnostic approach to myocardial injuries in a forensic pathology context.
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Affiliation(s)
- Katarzyna Michaud
- University Center of Legal Medicine Lausanne - Geneva, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
| | - Cristina Basso
- Cardiovascular Pathology Unit, Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padua, Padua, Italy
| | - Hans H de Boer
- Department of Forensic Medicine, Victorian Institute of Forensic Medicine, Monash University, Southbank, VIC, Australia
| | - Tony Fracasso
- University Center of Legal Medicine Lausanne - Geneva, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
- Geneva University Hospital and University of Geneva, Geneva, Switzerland
| | - Monica de Gaspari
- Cardiovascular Pathology Unit, Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padua, Padua, Italy
| | - Carla Giordano
- Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy
| | - Xiaofei Li
- Department of Pathology, Maastricht University Medical Center (MUMC), Maastricht, The Netherlands
| | - Joaquin Lucena
- Department of Pathology Institute of Legal Medicine and Forensic Sciences, Seville, Spain
| | - Pilar Molina
- Department of Pathology, Institute of Legal Medicine and Forensic Sciences, Valencia, Spain
- Research group CAFAMUSME, La Fe Health Research Institute, Valencia, Spain
| | - Sarah Parsons
- Department of Forensic Medicine, Victorian Institute of Forensic Medicine, Monash University, Southbank, VIC, Australia
| | - Mary N Sheppard
- CRY Cardiovascular Pathology Unit, Cardiovascular and Genetic Research Institute, City St George's, University of London, London, UK
| | - Allard C van der Wal
- Department of Pathology, Maastricht University Medical Center (MUMC), Maastricht, The Netherlands.
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Kotani Y, Lezzi M, Murru CP, Khanna AK, Zarbock A, Bellomo R, Landoni G. The Efficacy and Safety of Angiotensin II for Treatment of Vasoplegia in Critically Ill Patients: A Systematic Review. J Cardiothorac Vasc Anesth 2025; 39:653-665. [PMID: 39800604 DOI: 10.1053/j.jvca.2024.12.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Revised: 12/01/2024] [Accepted: 12/16/2024] [Indexed: 03/21/2025]
Abstract
OBJECTIVES To summarize evidence regarding intravenous angiotensin II administration in critical illness and provide an updated understanding of its effects on various organ dysfunction and renin-angiotensin system (RAS) biomarkers. DESIGN A systematic review. SETTING A search of PubMed, Embase, and the Cochrane Library from inception to May 3, 2024. Randomized controlled trials (RCTs), nonrandomized trials, quasi-randomized trials, observational studies, case reports, and case series were included. Comparative studies (RCTs and observational studies with comparator) were used for the main analysis. PARTICIPANTS Critically ill adults and children. INTERVENTIONS Intravenous angiotensin II administration. MEASUREMENTS AND MAIN RESULTS Fifty-nine studies with a total of 2,918 participants (5 RCTs, 15 observational studies, and 39 case reports or case series) were analyzed. Septic shock and cardiac surgery were the most common clinical conditions (14 studies for each). In 14 comparative studies (5 RCTs and 9 observational studies), mortality was not different from that in controls, except in 1 observational study. Several studies reported decreased renal replacement therapy use, improved oxygenation and blood pressure response, and decreased rate of myocardial injury with angiotensin II therapy. There was no increase in thrombotic events or adverse events. Angiotensin II therapy reduced renin and angiotensin I levels without affecting other RAS biomarkers. CONCLUSIONS Intravenous angiotensin II has been reported in almost 3000 critically ill patients with diverse types of shock. Despite unclear mortality impacts, angiotensin II seems to confer beneficial effects on several organ systems and RAS derangements, without increasing adverse events.
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Affiliation(s)
- Yuki Kotani
- Department of Intensive Care Medicine, Kameda Medical Center, Kamogawa, Japan
| | - Martina Lezzi
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Carlotta Pia Murru
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Ashish K Khanna
- Section on Critical Care Medicine, Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, NC; Perioperative Outcomes and Informatics Collaborative, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC; Outcomes Research Consortium, Houston, TX
| | - Alexander Zarbock
- Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Muenster, Muenster, Germany
| | - Rinaldo Bellomo
- Department of Intensive Care, Austin Hospital, Melbourne, Australia; Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia; Department of Critical Care, Melbourne Medical School, The University of Melbourne, Melbourne, Australia
| | - Giovanni Landoni
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy; School of Medicine, Vita-Salute San Raffaele University, Milan, Italy.
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Zakynthinos GE, Giamouzis G, Xanthopoulos A, Oikonomou E, Kalogeras K, Karavidas N, Dimeas IE, Gialamas I, Gounaridi MI, Siasos G, Vavuranakis M, Zakynthinos E, Tsolaki V. Septic Cardiomyopathy: Difficult Definition, Challenging Diagnosis, Unclear Treatment. J Clin Med 2025; 14:986. [PMID: 39941657 PMCID: PMC11818464 DOI: 10.3390/jcm14030986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 01/26/2025] [Accepted: 01/30/2025] [Indexed: 02/16/2025] Open
Abstract
Sepsis is a systemic inflammatory response syndrome of suspected or confirmed infectious origin, which frequently culminates in multiorgan failure, including cardiac involvement. Septic cardiomyopathy (SCM) remains a poorly defined clinical entity, lacking a formal or consensus definition and representing a significant knowledge gap in critical care medicine. It is an often-underdiagnosed complication of sepsis. The only widely accepted aspect of its definition is that SCM is a transient myocardial dysfunction occurring in patients with sepsis, which cannot be attributed to ischemia or pre-existing cardiac disease. The pathogenesis of SCM appears to be multifactorial, involving inflammatory cytokines, overproduction of nitric oxide, mitochondrial dysfunction, calcium homeostasis dysregulation, autonomic imbalance, and myocardial edema. Diagnosis primarily relies on echocardiography, with advanced tools such as tissue Doppler imaging (TDI) and global longitudinal strain (GLS) providing greater sensitivity for detecting subclinical dysfunction and guiding therapeutic decisions. Traditional echocardiographic findings, such as left ventricular ejection fraction measured by 2D echocardiography, often reflect systemic vasoplegia rather than intrinsic myocardial dysfunction, complicating accurate diagnosis. Right ventricular (RV) dysfunction, identified as a critical component of SCM in many studies, has multifactorial pathophysiology. Factors including septic cardiomyopathy itself, mechanical ventilation, hypoxemia, and hypercapnia-particularly in cases complicated by acute respiratory distress syndrome (ARDS)-increase RV afterload and exacerbate RV dysfunction. The prognostic value of cardiac biomarkers, such as troponins and natriuretic peptides, remains uncertain, as these markers primarily reflect illness severity rather than being specific to SCM. Treatment focuses on the early recognition of sepsis, hemodynamic optimization, and etiological interventions, as no targeted therapies currently exist. Emerging therapies, such as levosimendan and VA-ECMO, show potential in severe SCM cases, though further validation is needed. The lack of standardized diagnostic criteria, combined with the heterogeneity of sepsis presentations, poses significant challenges to the effective management of SCM. Future research should focus on developing cluster-based classification systems for septic shock patients by integrating biomarkers, echocardiographic findings, and clinical parameters. These advancements could clarify the underlying pathophysiology and enable tailored therapeutic strategies to improve outcomes for SCM patients.
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Affiliation(s)
- George E. Zakynthinos
- 3rd Department of Cardiology, “Sotiria” Chest Diseases Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (G.E.Z.); (E.O.); (K.K.); (I.G.); (M.I.G.); (G.S.); (M.V.)
| | - Grigorios Giamouzis
- Department of Cardiology, University Hospital of Larissa, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece; (G.G.); (A.X.)
| | - Andrew Xanthopoulos
- Department of Cardiology, University Hospital of Larissa, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece; (G.G.); (A.X.)
| | - Evangelos Oikonomou
- 3rd Department of Cardiology, “Sotiria” Chest Diseases Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (G.E.Z.); (E.O.); (K.K.); (I.G.); (M.I.G.); (G.S.); (M.V.)
| | - Konstantinos Kalogeras
- 3rd Department of Cardiology, “Sotiria” Chest Diseases Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (G.E.Z.); (E.O.); (K.K.); (I.G.); (M.I.G.); (G.S.); (M.V.)
| | - Nikitas Karavidas
- Critical Care Department, University Hospital of Larissa, Faculty of Medicine, University of Thessaly, Mezourlo, 41335 Larissa, Greece; (N.K.); (I.E.D.); (V.T.)
| | - Ilias E. Dimeas
- Critical Care Department, University Hospital of Larissa, Faculty of Medicine, University of Thessaly, Mezourlo, 41335 Larissa, Greece; (N.K.); (I.E.D.); (V.T.)
| | - Ioannis Gialamas
- 3rd Department of Cardiology, “Sotiria” Chest Diseases Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (G.E.Z.); (E.O.); (K.K.); (I.G.); (M.I.G.); (G.S.); (M.V.)
| | - Maria Ioanna Gounaridi
- 3rd Department of Cardiology, “Sotiria” Chest Diseases Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (G.E.Z.); (E.O.); (K.K.); (I.G.); (M.I.G.); (G.S.); (M.V.)
| | - Gerasimos Siasos
- 3rd Department of Cardiology, “Sotiria” Chest Diseases Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (G.E.Z.); (E.O.); (K.K.); (I.G.); (M.I.G.); (G.S.); (M.V.)
- Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Manolis Vavuranakis
- 3rd Department of Cardiology, “Sotiria” Chest Diseases Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (G.E.Z.); (E.O.); (K.K.); (I.G.); (M.I.G.); (G.S.); (M.V.)
| | - Epaminondas Zakynthinos
- Critical Care Department, University Hospital of Larissa, Faculty of Medicine, University of Thessaly, Mezourlo, 41335 Larissa, Greece; (N.K.); (I.E.D.); (V.T.)
| | - Vasiliki Tsolaki
- Critical Care Department, University Hospital of Larissa, Faculty of Medicine, University of Thessaly, Mezourlo, 41335 Larissa, Greece; (N.K.); (I.E.D.); (V.T.)
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Lanspa MJ, Khan A, Lyons PG, Gong MN, Naqvi AA, Dugar S, Duggal A, Johnson NJ, Schoeneck JH, Smith L, Bose S, Shapiro NI, Shvilkina T, Groat D, Jacobs JR, Olsen TD, Cannavina S, Knox DB, Hirshberg EL, Self WH, Brown SM. Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis-Study of Treatment's Echocardiographic Mechanisms (CLOVERS-STEM). Crit Care Explor 2024; 6:e1182. [PMID: 39652431 PMCID: PMC11631020 DOI: 10.1097/cce.0000000000001182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2024] Open
Abstract
IMPORTANCE Receipt of fluid and vasopressors, common treatments in septic shock, may affect cardiac function. OBJECTIVES We sought to determine whether a liberal or restrictive fluid resuscitation strategy was associated with changes in cardiac function. DESIGN We prospectively studied a subset of patients enrolled in the Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS) trial, performing echocardiography at baseline and at 24 hours after randomization. Among patients who had an echocardiogram performed at 24 hours, we measured left ventricular global longitudinal strain (LV GLS) and right ventricular free-wall longitudinal strain (RVFWLS). We performed linear regressions with dependent variables of LV GLS, change in LV GLS (ΔLV GLS), and RVFWLS using treatment assignment as an independent variable. We adjusted for ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity, mean arterial pressure, and history of congestive heart failure and myocardial infarction. SETTING Emergency department and ICUs. PATIENTS Adults with sepsis enrolled in the CLOVERS trial. MAIN OUTCOMES AND MEASURES We enrolled 180 patients. Our analytic cohort comprised 131 patients with an echocardiogram performed at 24 hours. We observed no differences between treatment arms with respect to demographic, clinical, or echocardiographic data at baseline. We observed no association between restrictive fluid assignment and LV GLS (coefficient, 1.22; p = 0.23), ΔLV GLS (-1.97; p = 0.27), or RVFWLS (2.33; p = 0.19). CONCLUSIONS AND RELEVANCE In a subset of patients enrolled in CLOVERS, we observed no association between receipt of fluid and vasopressors and short-term changes in cardiac function. Decreased enrollment may limit inferences.
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Affiliation(s)
- Michael J. Lanspa
- Intermountain, Critical Care Echocardiography Service, Salt Lake City, UT
| | - Akram Khan
- Division of Pulmonary and Critical Care Medicine, Oregon Health & Sciences University, Portland, OR
| | - Patrick G. Lyons
- Division of Pulmonary and Critical Care Medicine, Oregon Health & Sciences University, Portland, OR
| | - Michelle N. Gong
- Division of Critical Care Medicine, Montefiore Medical Center, New York, NY
| | - Ali A. Naqvi
- Division of Critical Care Medicine, Montefiore Medical Center, New York, NY
| | - Siddharth Dugar
- Department of Critical Care, Cleveland Clinic, Cleveland, OH
| | - Abhijit Duggal
- Department of Critical Care, Cleveland Clinic, Cleveland, OH
| | | | - Jacob H. Schoeneck
- Department of Emergency Medicine, Wake Forest Baptist, Winston-Salem, NC
| | - Lane Smith
- Department of Emergency Medicine, Wake Forest Baptist, Winston-Salem, NC
| | - Somnath Bose
- Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA
| | - Nathan I. Shapiro
- Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA
| | - Tatyana Shvilkina
- Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA
| | - Danielle Groat
- Intermountain, Critical Care Echocardiography Service, Salt Lake City, UT
| | - Jason R. Jacobs
- Intermountain, Critical Care Echocardiography Service, Salt Lake City, UT
| | - Troy D. Olsen
- Intermountain, Critical Care Echocardiography Service, Salt Lake City, UT
| | - Steven Cannavina
- Intermountain, Critical Care Echocardiography Service, Salt Lake City, UT
| | - Daniel B. Knox
- Intermountain, Critical Care Echocardiography Service, Salt Lake City, UT
| | | | - Wesley H. Self
- Department of Emergency Medicine, Vanderbilt University, Nashville, TN
| | - Samuel M. Brown
- Intermountain, Critical Care Echocardiography Service, Salt Lake City, UT
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7
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Refaie MMM, El-Hussieny M, Bayoumi AMA, Abdelraheem WM, Abdel-Hakeem EA, Shehata S. Sacubitril/valsartan alleviates sepsis-induced myocardial injury in rats via dual angiotensin receptor-neprilysin inhibition and modulation of inflammasome/caspase 1/IL1β pathway. Eur J Pharmacol 2024; 979:176834. [PMID: 39038638 DOI: 10.1016/j.ejphar.2024.176834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Revised: 06/30/2024] [Accepted: 07/18/2024] [Indexed: 07/24/2024]
Abstract
Sepsis is a life-threatening situation that ultimately affects cardiac function, leading to cardiomyopathy and myocardial injury as a result of uncontrolled response to infection.Till now, there is limited effective treatment to rescue those cases. Thus, novel therapeutic strategies should be identified to achieve better outcomes for septic patients. For the first time, we aimed to evaluate the effect of sacubitril/valsartan (Sac/Val) on sepsis-induced cardiac injury. Wistar male adult albino rats were randomly divided into four groups; Group I received the vehicle; Group II was given the vehicle plus 1 ml saline containing viable Escherichia coli (E. coli) (2.1 × 109 cfu) by intraperitoneal (i.p.) injection on the 1st and 2nd days; Group III received i.p. injection as group II plus oral administration of Sac/Val (30 mg/kg/day) and Nitro- ω-L-arginine (L-NNA) (25 mg/kg/day) for 7 days. Group IV was administered i.p. injection as group II plus oral administration of Sac/Val (30 mg/kg/day) for 7 days. Our data (n = 10) revealed successful induction of sepsis as it showed a significant increase in the measured cardiac enzymes, malondialdehyde (MDA), angiotensin II (Ang II), neprilysin, inflammasome, caspase 1, interleukin (IL)1β, and caspase 3 with cardiac histopathological changes, but there was a significant decrease in the antioxidants and blood pressure (BP). Co-administration of Sac/Val could obviously improve these changes. Interestingly, L-NNA given group showed a decrease in the cardioprotective effect of Sac/Val. Sac/Val could ameliorate sepsis induced cardiac damage via inhibition of Ang II and neprilysin with anti-inflammatory, anti-oxidant and anti-apoptotic properties.
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Affiliation(s)
| | - Maram El-Hussieny
- Department of Pathology, Faculty of Medicine, Minia University, 61511, El-Minia, Egypt.
| | - Asmaa M A Bayoumi
- Department of Biochemistry, Faculty of Pharmacy, Minia University, 61519, El-Minia, Egypt.
| | - Wedad M Abdelraheem
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Minia University, 61511, El-Minia, Egypt.
| | - Elshymaa A Abdel-Hakeem
- Department of Medical Physiology, Faculty of Medicine, Minia University, 61511, El-Minia, Egypt.
| | - Sayed Shehata
- Department of Cardiology, Faculty of Medicine, Minia University, 61511, El-Minia, Egypt.
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8
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Zhang L, Yu Y, Wu T, Pan T, Qu H, Wu J, Tan R. Effectiveness of β-blockers in improving 28-day mortality in septic shock: insights from subgroup analysis and retrospective observational study. Front Cardiovasc Med 2024; 11:1438798. [PMID: 39290214 PMCID: PMC11405245 DOI: 10.3389/fcvm.2024.1438798] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2024] [Accepted: 08/21/2024] [Indexed: 09/19/2024] Open
Abstract
Background In recent years, septic shock remains a common fatal disease in the intensive care unit (ICU). After sufficient fluid resuscitation, some patients still experience tachycardia, which may lead to adverse effects on cardiac function. However, the use of β-blockers in the treatment of septic shock remains controversial. Thus, the purpose of this study is to evaluate the efficacy of β-blockers in the treatment of patients with septic shock and explore the most appropriate patient subgroups for this treatment. Methods This retrospective observational study enrolled septic shock patients from the Medical Information Mart for Intensive Care (MIMIC)-IV and used propensity score matching (PSM) to balance some baseline differences between patients with and without β-blockers treatment. The primary outcome was the 28-day mortality. Length of stay (LOS) in the ICU and hospital, and the degree of support for organs such as circulatory, respiratory and renal systems were also assessed. Subgroup analysis and multivariate logistic regression were performed to determine the relationship between β-blockers therapy and 28-day mortality in different patient groups. Results A total of 4,860 septic shock patients were enrolled in this study and 619 pairs were finally matched after PSM. Our analysis revealed that β-blocker therapy was associated with a significant improvement in 28-day mortality (21.5% vs. 27.1%; P = 0.020) and led to a prolonged LOS in both the ICU and hospital. Subgroup analysis indicated that there was an interaction between cardiovascular diseases and β-blocker therapy in patients with septic shock. Patients with pre-existing heart disease or atrial arrhythmias were more likely to derive benefits from β-blocker treatment. Conclusion We found β-blockers therapy was effective to improve 28-day mortality in patients with septic shock. Patients in the subgroup with cardiovascular diseases were more likely to benefit from β-blockers in mortality.
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Affiliation(s)
- Ling Zhang
- Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yue Yu
- Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tong Wu
- Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tingting Pan
- Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hongping Qu
- Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jingyi Wu
- Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ruoming Tan
- Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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9
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Pruszczyk A, Zawadka M, Andruszkiewicz P, LaVia L, Herpain A, Sato R, Dugar S, Chew MS, Sanfilippo F. Mortality in patients with septic cardiomyopathy identified by longitudinal strain by speckle tracking echocardiography: An updated systematic review and meta-analysis with trial sequential analysis. Anaesth Crit Care Pain Med 2024; 43:101339. [PMID: 38128732 DOI: 10.1016/j.accpm.2023.101339] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Revised: 11/27/2023] [Accepted: 12/04/2023] [Indexed: 12/23/2023]
Abstract
BACKGROUND Septic cardiomyopathy is associated with poor outcomes but its definition remains unclear. In a previous meta-analysis, left ventricular (LV) longitudinal strain (LS) showed significant prognostic value in septic patients, but findings were not robust due to a limited number of studies, differences in effect size and no adjustment for confounders. METHODS We conducted an updated systematic review (PubMed and Scopus up to 14.02.2023) and meta-analysis to investigate the association between LS and survival in septic patients. We included studies reporting global (from three apical views) or regional LS (one or two apical windows). A secondary analysis evaluated the association between LV ejection fraction (EF) and survival using data from the selected studies. RESULTS We included fourteen studies (1678 patients, survival 69.6%) and demonstrated an association between better performance (more negative LS) and survival with a mean difference (MD) of -1.45%[-2.10, -0.80] (p < 0.0001;I2 = 42%). No subgroup differences were found stratifying studies according to number of views used to calculate LS (p = 0.31;I2 = 16%), severity of sepsis (p = 0.42;I2 = 0%), and sepsis criteria (p = 0.59;I2 = 0%). Trial sequential analysis and sensitivity analyses confirmed the primary findings. Grade of evidence was low. In the included studies, thirteen reported LVEF and we found an association between higher LVEF and survival (MD = 2.44% [0.44,4.45]; p = 0.02;I2 = 42%). CONCLUSIONS We confirmed that more negative LS values are associated with higher survival in septic patients. The clinical relevance of this difference and whether the use of LS may improve understanding of septic cardiomyopathy and prognostication deserve further investigation. The association found between LVEF and survival is of unlikely clinical meaning. REGISTRATION PROSPERO number CRD42023432354.
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Affiliation(s)
- Andrzej Pruszczyk
- 2nd Department of Anesthesiology and Intensive Care, Medical University of Warsaw, Poland
| | - Mateusz Zawadka
- 2nd Department of Anesthesiology and Intensive Care, Medical University of Warsaw, Poland
| | - Pawel Andruszkiewicz
- 2nd Department of Anesthesiology and Intensive Care, Medical University of Warsaw, Poland
| | - Luigi LaVia
- Department of Anesthesia and Intensive Care, "Policlinico-San Marco" University Hospital, Catania, Italy
| | - Antoine Herpain
- Department of Intensive Care, St.-Pierre University Hospital, Université Libre de Bruxelles, 1050 Brussels, Belgium; Experimental Laboratory of Intensive Care, Université Libre de Bruxelles, 1050 Brussels, Belgium
| | - Ryota Sato
- Department of Critical Care Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, OH, United States
| | - Siddharth Dugar
- Department of Critical Care Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, OH, United States
| | - Michelle S Chew
- Department of Anaesthesia and Intensive Care, Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Filippo Sanfilippo
- Department of Anesthesia and Intensive Care, "Policlinico-San Marco" University Hospital, Catania, Italy; Department of General Surgery and Medico-Surgical Specialties, School of Anaesthesia and Intensive Care, University of Catania, Catania, Italy.
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10
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Sato K, Wildi K, Chan J, Palmieri C, Obonyo NG, Heinsar S, Liu K, Livingstone S, Sato N, Ainola C, Abbate G, Bouquet M, Wilson E, Passmore M, Hyslop K, Platts DG, Suen J, Bassi GL, Fraser JF. A novel speckle-tracking echocardiography parameter assessing left ventricular afterload. Eur J Clin Invest 2024; 54:e14106. [PMID: 37822060 PMCID: PMC7616760 DOI: 10.1111/eci.14106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Revised: 09/19/2023] [Accepted: 09/28/2023] [Indexed: 10/13/2023]
Abstract
BACKGROUND Left ventricular stroke work index (LVSWI) and afterload-related cardiac performance (ACP) consider left ventricular (LV) afterload and could be better prognosticators in septic cardiomyopathy. However, their invasive nature prevents their routine clinical applications. This study aimed to investigate (1) whether a proposed speckle-tracking echocardiography parameter, Pressure-Strain Product (PSP), can non-invasively predict catheter-based LVSWI, ACP and serum lactate in an ovine model of septic cardiomyopathy; and (2) whether PSP can distinguish the sub-phenotypes of acute respiratory distress syndrome (ARDS) with or without sepsis-like conditions. METHODS Sixteen sheep with ARDS were randomly assigned to either (1) sepsis-like (n = 8) or (2) non-sepsis-like (n = 8) group. Each ARDS and sepsis-like condition was induced by intravenous infusion of oleic acid and lipopolysaccharide, respectively. Pulmonary artery catheter-based LVSWI (the product of stroke work index, mean arterial pressure and .0136), ACP (the percentage of cardiac output measured to cardiac output predicted as normal) and serum lactate were measured simultaneously with transthoracic echocardiography. Two PSP indices were calculated by multiplying the mean arterial blood pressure and either global circumferential strain (PSPcirc) or radial strain (PSPrad). RESULTS PSPcirc showed a significant correlation with LVSWI (r2 = .66, p < .001) and ACP (r2 = .82, p < .001) in the sepsis-like group. Although PSP could not distinguish subphenotypes, PSPcirc predicted LVSWI (AUC .86) and ACP (AUC .88), and PSPrad predicted serum lactate (AUC .75) better than LV ejection fraction, global circumferential and radial strain. CONCLUSIONS A novel PSP has the potential to non-invasively predict catheter-based LVSWI and ACP, and was associated with serum lactate in septic cardiomyopathy.
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Affiliation(s)
- Kei Sato
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, Queensland, Australia
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Karin Wildi
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, Queensland, Australia
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
- Department of Intensive Care Medicine, University Hospital Basel, Basel, Switzerland
- Faculty of Medicine, University of Basel, Basel, Switzerland
| | - Jonathan Chan
- Cardiology Department, The Prince Charles Hospital, Brisbane, Queensland, Australia
- Griffith University, School of Medicine, Brisbane, Queensland, Australia
| | - Chiara Palmieri
- The University of Queensland, School of Veterinary Science, Gatton, Australia
| | - Nchafatso G. Obonyo
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, Queensland, Australia
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
- DeAL/KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya
- Wellcome Trust Centre for Global Health Research, Imperial College London, London, UK
| | - Silver Heinsar
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, Queensland, Australia
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Keibun Liu
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, Queensland, Australia
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Samantha Livingstone
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, Queensland, Australia
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Noriko Sato
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, Queensland, Australia
| | - Carmen Ainola
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, Queensland, Australia
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Gabriella Abbate
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, Queensland, Australia
| | - Mahé Bouquet
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, Queensland, Australia
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Emily Wilson
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, Queensland, Australia
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Margaret Passmore
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, Queensland, Australia
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Kieran Hyslop
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, Queensland, Australia
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - David G. Platts
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, Queensland, Australia
- Cardiology Department, The Prince Charles Hospital, Brisbane, Queensland, Australia
| | - Jacky Suen
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, Queensland, Australia
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Gianluigi Li Bassi
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, Queensland, Australia
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - John F. Fraser
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, Queensland, Australia
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
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11
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Fan Y, Guan B, Xu J, Zhang H, Yi L, Yang Z. Role of toll-like receptor-mediated pyroptosis in sepsis-induced cardiomyopathy. Biomed Pharmacother 2023; 167:115493. [PMID: 37734261 DOI: 10.1016/j.biopha.2023.115493] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Revised: 09/08/2023] [Accepted: 09/12/2023] [Indexed: 09/23/2023] Open
Abstract
Sepsis, a life-threatening dysregulated status of the host response to infection, can cause multiorgan dysfunction and mortality. Sepsis places a heavy burden on the cardiovascular system due to the pathological imbalance of hyperinflammation and immune suppression. Myocardial injury and cardiac dysfunction caused by the aberrant host responses to pathogens can lead to cardiomyopathy, one of the most critical complications of sepsis. However, many questions about the specific mechanisms and characteristics of this complication remain to be answered. The causes of sepsis-induced cardiac dysfunction include abnormal cardiac perfusion, myocardial inhibitory substances, autonomic dysfunction, mitochondrial dysfunction, and calcium homeostasis dysregulation. The fight between the host and pathogens acts as the trigger for sepsis-induced cardiomyopathy. Pyroptosis, a form of programmed cell death, plays a critical role in the progress of sepsis. Toll-like receptors (TLRs) act as pattern recognition receptors and participate in innate immune pathways that recognize damage-associated molecular patterns as well as pathogen-associated molecular patterns to mediate pyroptosis. Notably, pyroptosis is tightly associated with cardiac dysfunction in sepsis and septic shock. In line with these observations, induction of TLR-mediated pyroptosis may be a promising therapeutic approach to treat sepsis-induced cardiomyopathy. This review focuses on the potential roles of TLR-mediated pyroptosis in sepsis-induced cardiomyopathy, to shed light on this promising therapeutic approach, thus helping to prevent and control septic shock caused by cardiovascular disorders and improve the prognosis of sepsis patients.
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Affiliation(s)
- Yixuan Fan
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China; Intensive Care Unit, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Baoyi Guan
- Department of Internal Medicine-Cardiovascular, The First Affiliated Hospital of Guangzhou University of Chinese Medicine
| | - Jianxing Xu
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China; Intensive Care Unit, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - He Zhang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China; National Clinical Research Center for Chinese Medicine Cardiology, Beijing, China
| | - Liang Yi
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China; Intensive Care Unit, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
| | - Zhixu Yang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China; Intensive Care Unit, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
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12
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See EJ, Clapham C, Liu J, Khasin M, Liskaser G, Chan JW, Serpa Neto A, Costa Pinto R, Bellomo R. A PILOT STUDY OF ANGIOTENSIN II AS PRIMARY VASOPRESSOR IN CRITICALLY ILL ADULTS WITH VASODILATORY HYPOTENSION: THE ARAMIS STUDY. Shock 2023; 59:691-696. [PMID: 36930693 DOI: 10.1097/shk.0000000000002109] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/18/2023]
Abstract
ABSTRACT Objective: The aim of the study is to evaluate the efficacy and safety of using angiotensin II (Ang2) as primary vasopressor for vasodilatory hypotension. Methods: This was a prospective observational study of critically ill adults admitted to an academic intensive care unit (ICU) with vasodilatory hypotension. We treated 40 patients with Ang2 as primary vasopressor and compared them with 80 matched controls who received conventional vasopressors (norepinephrine, vasopressin, metaraminol, epinephrine, or combinations). Results : Mean age was 63 years and median Acute Physiology and Chronic Health Evaluation III score was 65. Ang2 patients had lower ICU mortality (10% vs 26%, P = 0.04); however, their 28- and 90-day mortality was not significantly different (18% vs 29%, P = 0.18; 22% vs 30%, P = 0.39). Peak serum creatinine levels were similar (128 vs 126 μmol/L, P = 0.81), as was the incidence and stage of acute kidney injury (70% vs 74%, P = 0.66), requirement for continuous renal replacement therapy (14% vs 13%, P = 0.84), and risk of major adverse kidney events at 7 days (20% vs 29%, P = 0.30). However, Ang2 patients with prior exposure to renin angiotensin aldosterone system inhibitors had a lower peak serum creatinine ( P = 0.03 for interaction) than conventional vasopressors patients, and serum troponin elevations were less common with Ang2 (8% vs 22%, P = 0.04). The incidence of thromboembolic complications was similar. Conclusions: Primary Ang2 administration in vasodilatory hypotension did not seem harmful compared with conventional vasopressors. Although Ang2 did not decrease peak serum creatinine levels or major adverse kidney events, its effects on intensive care unit survival, serum troponin, and renal function in patients on renin angiotensin aldosterone system inhibitors warrant further exploration in randomized trials (ACTRN12621000281897).
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Affiliation(s)
| | - Caroline Clapham
- Department of Intensive Care, Austin Hospital, Heidelberg, Australia
| | - Jasmine Liu
- Department of Intensive Care, Austin Hospital, Heidelberg, Australia
| | - Monique Khasin
- School of Medicine, University of Melbourne, Melbourne, Australia
| | - Grace Liskaser
- Department of Intensive Care, Austin Hospital, Heidelberg, Australia
| | - Jian Wen Chan
- Department of Intensive Care, Austin Hospital, Heidelberg, Australia
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13
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Enomoto Y, Matsuda Y, Nagamine Y, Goto T. Venoarterial-extra corporeal membrane oxygenation-assisted parathyroidectomy for hypercalcemic crisis due to parathyroid carcinoma complicated by severe circulatory and respiratory failure: a case report. JA Clin Rep 2023; 9:14. [PMID: 36914845 PMCID: PMC10011232 DOI: 10.1186/s40981-023-00606-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 03/04/2023] [Accepted: 03/07/2023] [Indexed: 03/16/2023] Open
Abstract
BACKGROUND Hypercalcemia crisis is a rare but severe form of hypercalcemia complicated by multiple organ failure. Hypercalcemia crisis due to hyperparathyroidism is commonly caused by a parathyroid tumor, which often requires surgical resection. However, there are no clear recommendations on when the surgery should be performed. CASE PRESENTATION A 64-year-old female patient developed hyperparathyroidism due to a parathyroid tumor and hypercalcemic crisis, which was complicated by severe circulatory and respiratory failure refractory to medical therapy, and an emergent surgery was planned to resect the parathyroid tumor. To prevent intraoperative circulatory and respiratory collapse, venoarterial-extra corporeal membrane oxygenation (VA-ECMO) was introduced, resulting in a safe operation and anesthetic management. CONCLUSIONS In patients with hypercalcemic crisis complicated by severe circulatory and respiratory failure, induction of prophylactic VA-ECMO was useful for safe anesthetic management. Surgical resection should be performed as soon as the diagnosis is made before VA-ECMO is required.
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Affiliation(s)
- Yuria Enomoto
- Department of Anesthesiology and Critical Care Medicine, Yokohama City University Hospital, 3-9 Fukuura, Kanazawa-Ku, Kanagawa, 236-0004, Yokohama, Japan
| | - Yuko Matsuda
- Department of Anesthesiology and Critical Care Medicine, Yokohama City University Hospital, 3-9 Fukuura, Kanazawa-Ku, Kanagawa, 236-0004, Yokohama, Japan
| | - Yusuke Nagamine
- Department of Anesthesiology and Critical Care Medicine, Yokohama City University Hospital, 3-9 Fukuura, Kanazawa-Ku, Kanagawa, 236-0004, Yokohama, Japan.
| | - Takahisa Goto
- Department of Anesthesiology and Critical Care Medicine, Yokohama City University Hospital, 3-9 Fukuura, Kanazawa-Ku, Kanagawa, 236-0004, Yokohama, Japan
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14
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Carbone F, Liberale L, Preda A, Schindler TH, Montecucco F. Septic Cardiomyopathy: From Pathophysiology to the Clinical Setting. Cells 2022; 11:2833. [PMID: 36139408 PMCID: PMC9496713 DOI: 10.3390/cells11182833] [Citation(s) in RCA: 69] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 09/05/2022] [Accepted: 09/07/2022] [Indexed: 11/21/2022] Open
Abstract
The onset of cardiomyopathy is a common feature in sepsis, with relevant effects on its pathophysiology and clinical care. Septic cardiomyopathy is characterized by reduced left ventricular (LV) contractility eventually associated with LV dilatation with or without right ventricle failure. Unfortunately, such a wide range of ultrasonographic findings does not reflect a deep comprehension of sepsis-induced cardiomyopathy, but rather a lack of consensus about its definition. Several echocardiographic parameters intrinsically depend on loading conditions (both preload and afterload) so that it may be challenging to discriminate which is primitive and which is induced by hemodynamic perturbances. Here, we explore the state of the art in sepsis-related cardiomyopathy. We focus on the shortcomings in its definition and point out how cardiac performance dynamically changes in response to different hemodynamic clusters. A special attention is also given to update the knowledge about molecular mechanisms leading to myocardial dysfunction and that recall those of myocardial hibernation. Ultimately, the aim of this review is to highlight the unsolved issue in the field of sepsis-induced cardiomyopathy as their implementation would lead to improve risk stratification and clinical care.
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Affiliation(s)
- Federico Carbone
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa-Italian Cardiovascular Network, 16132 Genoa, Italy
| | - Luca Liberale
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa-Italian Cardiovascular Network, 16132 Genoa, Italy
| | - Alberto Preda
- Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Thomas Hellmut Schindler
- Mallinckrodt Institute of Radiology, Division of Nuclear Medicine, School of Medicine, Washington University, Saint Louis, MO 63110, USA
| | - Fabrizio Montecucco
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa-Italian Cardiovascular Network, 16132 Genoa, Italy
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15
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Owen A, Patel JM, Parekh D, Bangash MN. Mechanisms of Post-critical Illness Cardiovascular Disease. Front Cardiovasc Med 2022; 9:854421. [PMID: 35911546 PMCID: PMC9334745 DOI: 10.3389/fcvm.2022.854421] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 06/22/2022] [Indexed: 11/13/2022] Open
Abstract
Prolonged critical care stays commonly follow trauma, severe burn injury, sepsis, ARDS, and complications of major surgery. Although patients leave critical care following homeostatic recovery, significant additional diseases affect these patients during and beyond the convalescent phase. New cardiovascular and renal disease is commonly seen and roughly one third of all deaths in the year following discharge from critical care may come from this cluster of diseases. During prolonged critical care stays, the immunometabolic, inflammatory and neurohumoral response to severe illness in conjunction with resuscitative treatments primes the immune system and parenchymal tissues to develop a long-lived pro-inflammatory and immunosenescent state. This state is perpetuated by persistent Toll-like receptor signaling, free radical mediated isolevuglandin protein adduct formation and presentation by antigen presenting cells, abnormal circulating HDL and LDL isoforms, redox and metabolite mediated epigenetic reprogramming of the innate immune arm (trained immunity), and the development of immunosenescence through T-cell exhaustion/anergy through epigenetic modification of the T-cell genome. Under this state, tissue remodeling in the vascular, cardiac, and renal parenchymal beds occurs through the activation of pro-fibrotic cellular signaling pathways, causing vascular dysfunction and atherosclerosis, adverse cardiac remodeling and dysfunction, and proteinuria and accelerated chronic kidney disease.
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Affiliation(s)
- Andrew Owen
- Department of Critical Care, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham, United Kingdom
- Birmingham Acute Care Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom
| | - Jaimin M. Patel
- Department of Critical Care, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham, United Kingdom
- Birmingham Acute Care Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom
| | - Dhruv Parekh
- Department of Critical Care, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham, United Kingdom
- Birmingham Acute Care Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom
| | - Mansoor N. Bangash
- Department of Critical Care, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham, United Kingdom
- Birmingham Acute Care Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom
- *Correspondence: Mansoor N. Bangash
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Cocchi MN, Dargin J, Chase M, Patel PV, Grossestreuer A, Balaji L, Liu X, Moskowitz A, Berg K, Donnino MW. Esmolol to Treat the Hemodynamic Effects of Septic Shock: A Randomized Controlled Trial. Shock 2022; 57:508-517. [PMID: 35066509 PMCID: PMC10448435 DOI: 10.1097/shk.0000000000001905] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
INTRODUCTION Septic shock is often characterized by tachycardia and a hyperdynamic hemodynamic profile. Use of the beta antagonist esmolol has been proposed as a therapy to lower heart rate, thereby improving diastolic filling time and improving cardiac output, resulting in a reduction in vasopressor support. METHODS We conducted a two-center, open-label, randomized, Phase II trial comparing esmolol to placebo in septic shock patients with tachycardia. The primary endpoint was improvement in hemodynamics as measured by the difference in norepinephrine equivalent dose (NED) between groups at 6 hours after initiation of study drug. Secondary outcomes included assessing differences in inflammatory biomarkers and oxygen consumption (VO2). RESULTS A total of 1,122 patients were assessed for eligibility and met inclusion criteria; 42 underwent randomization, and 40 received study interventions (18 in the esmolol arm and 22 in the usual care arm). The mean NED at 6 h was 0.30 ± 0.17 mcg/kg/min in the esmolol arm compared to 0.21 ± 0.19 in the standard care arm (P = 0.15). There was no difference in number of shock free days between the esmolol (2, IQR 0, 5) and control groups (2.5, IQR 0, 6) (P = 0.32). There were lower levels of C-reactive protein at 12 and 24 h in the esmolol arm, as well as a statistically significant difference in trend over time between groups. There were no differences in terms of IL-4, IL-6, IL-10, and TNFα. Among a subset who underwent VO2 monitoring, there was decreased oxygen consumption in the esmolol patients; the mean difference between groups at 24 h was -2.07 mL/kg/min (95% CI -3.82, -0.31) (P = 0.02), with a significant difference for the trend over time (P < 0.01). CONCLUSION Among patients with septic shock, infusion of esmolol did not improve vasopressor requirements or time to shock reversal. Esmolol was associated with decreased levels of C-reactive protein over 24 h. TRIAL REGISTRATION www.clinicaltrials.gov. Registered February 24, 2015, https://clinicaltrials.gov/ct2/show/NCT02369900.
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Affiliation(s)
- Michael N. Cocchi
- Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
- Department of Anesthesia Critical Care, Division of Critical Care, Beth Israel Deaconess Medical Center, Boston, Massachusetts
- Center for Resuscitation Science, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - James Dargin
- Department of Medicine, Division of Pulmonary and Critical Care Medicine, Lahey Hospital and Medical Center, Burlington, Massachusetts
| | - Maureen Chase
- Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
- Center for Resuscitation Science, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Parth V. Patel
- Center for Resuscitation Science, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Anne Grossestreuer
- Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
- Center for Resuscitation Science, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Lakshman Balaji
- Center for Resuscitation Science, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Xiaowen Liu
- Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
- Center for Resuscitation Science, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Ari Moskowitz
- Center for Resuscitation Science, Beth Israel Deaconess Medical Center, Boston, Massachusetts
- Department of Medicine, Division of Critical Care Medicine, Montefiore Medical Center, Bronx, New York
| | - Katherine Berg
- Center for Resuscitation Science, Beth Israel Deaconess Medical Center, Boston, Massachusetts
- Department of Medicine, Division of Pulmonary Critical Care, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Michael W. Donnino
- Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
- Center for Resuscitation Science, Beth Israel Deaconess Medical Center, Boston, Massachusetts
- Department of Medicine, Division of Pulmonary Critical Care, Beth Israel Deaconess Medical Center, Boston, Massachusetts
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Boissier F, Aissaoui N. Septic cardiomyopathy: Diagnosis and management. JOURNAL OF INTENSIVE MEDICINE 2021; 2:8-16. [PMID: 36789232 PMCID: PMC9923980 DOI: 10.1016/j.jointm.2021.11.004] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 11/14/2021] [Accepted: 11/25/2021] [Indexed: 12/12/2022]
Abstract
There is an extensive body of literature focused on sepsis-induced myocardial dysfunction, but results are conflicting and no objective definition of septic cardiomyopathy (SCM) has been established. SCM may be defined as a sepsis-associated acute syndrome of non-ischemic cardiac dysfunction with systolic and/or diastolic left ventricular (LV) dysfunction and/or right ventricular dysfunction. Physicians should consider this diagnosis in patients with sepsis-associated organ dysfunction, and particularly in cases of septic shock that require vasopressors. Echocardiography is currently the gold standard for diagnosis of SCM. Left ventricular ejection fraction is the most common parameter used to describe LV function in the literature, but its dependence on loading conditions, particularly afterload, limits its use as a measure of intrinsic myocardial contractility. Therefore, repeated echocardiography evaluation is mandatory. Evaluation of global longitudinal strain (GLS) may be more sensitive and specific for SCM than LV ejection fraction (LVEF). Standard management includes etiological treatment, adapted fluid resuscitation, use of vasopressors, and monitoring. Use of inotropes remains uncertain, and heart rate control could be an option in some patients.
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Affiliation(s)
- Florence Boissier
- Service de Médecine Intensive Réanimation, CHU de Poitiers, Poitiers 86021, France,Université de Poitiers, Poitiers INSERM CIC 1402 (ALIVE group), France
| | - Nadia Aissaoui
- Service de Médecine Intensive Réanimation, Hôpital Cochin, APHP, Paris 75014, France,Université de Paris, Paris Cardiovascular Research Center, INSERM U970, Paris 75015, France,Corresponding author: Nadia Aissaoui, Service de Médecine Intensive–Réanimation, Hôpital Cochin Assistance Publique–Hôpitaux de Paris, 27 Rue du Faubourg Saint-Jacques, 75014 Paris, France.
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Abou Dagher G, Bou Chebl R, Safa R, Assaf M, Kattouf N, Hajjar K, El Khuri C, Berbari I, Makki M, El Sayed M. The prevalence of bacteremia in out of hospital cardiac arrest patients presenting to the emergency department of a tertiary care hospital. Ann Med 2021; 53:1207-1215. [PMID: 34282693 PMCID: PMC8293943 DOI: 10.1080/07853890.2021.1953703] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 07/05/2021] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Out-of-hospital cardiac arrest (OHCA) remains one of the most common causes of death. There is a scarcity of evidence concerning the prevalence of bacteraemia in cardiac arrest patients presenting to the Emergency Department (ED). We aimed to determine the prevalence of bacteraemia in OHCA patients presenting to the ED, as well as study the association between bacteraemia and in-hospital mortality in OHCA patients. In addition, the association between antibiotic use during resuscitation and in-hospital mortality was examined. METHODS AND RESULTS This was a study of 200 adult OHCA patients who presented to the ED between 2015 and 2019. Bacteraemia was confirmed if at least one of the blood culture bottles grew a non-skin flora pathogen or if two blood culture bottles grew a skin flora pathogen from two different sites. The prevalence of bacteraemia was 46.5%. Gram positive bacteria, specifically Staphylococcus species, were the most common pathogens isolated from the bacteremic group. 42 patients survived to hospital admission. The multivariate analysis revealed that there was no association between bacteraemia and hospital mortality in OHCA patients (OR = 1.3, 95% CI= 0.2-9.2) with a p-value of .8. There was no association between antibiotic administration during resuscitation and hospital mortality (OR = 0.6, 95% CI= 0.1 - 3.8) with a p-value of .6. CONCLUSION In our study, the prevalence of bacteraemia among OHCA patients presenting to the ED was found to be 46.5%. Bacteremic and non-bacteremic OHCA patients had similar initial baseline characteristics and laboratory parameters except for higher serum creatinine and BUN in the bacteremic group. In OHCA patients who survived their ED stay there was no association between hospital mortality and bacteraemia or antibiotic administration during resuscitation. There is a need for randomised controlled trials with a strong patient oriented primary outcome to better understand the association between in-hospital mortality and bacteraemia or antibiotic administration in OHCA patients.KEY MESSAGESWe aimed to determine the prevalence of bacteraemia in OHCA patients presenting to the Emergency Department. In our study, we found that 46.5% of patients presenting to our ED with OHCA were bacteremic.Bacteremic and non-bacteremic OHCA patients had similar initial baseline characteristics and laboratory parameters except for higher serum creatinine and BUN in the bacteremic group.We found no association between bacteraemia and hospital mortality. There was no association between antibiotic administration during resuscitation and hospital mortality.There is a need for randomised controlled trials with a strong patient oriented primary outcome to better understand the association between in-hospital mortality and bacteraemia or antibiotic administration in OHCA patients.
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Affiliation(s)
- Gilbert Abou Dagher
- Department of Emergency Medicine, American University of Beirut, Beirut, Lebanon
| | - Ralph Bou Chebl
- Department of Emergency Medicine, American University of Beirut, Beirut, Lebanon
| | - Rawan Safa
- Department of Emergency Medicine, American University of Beirut, Beirut, Lebanon
| | - Mohammad Assaf
- Department of Emergency Medicine, American University of Beirut, Beirut, Lebanon
| | - Nadim Kattouf
- Department of Emergency Medicine, American University of Beirut, Beirut, Lebanon
| | - Karim Hajjar
- Department of Emergency Medicine, American University of Beirut, Beirut, Lebanon
| | - Christopher El Khuri
- Department of Emergency Medicine, American University of Beirut, Beirut, Lebanon
| | - Iskandar Berbari
- Department of Emergency Medicine, American University of Beirut, Beirut, Lebanon
| | - Maha Makki
- Department of Internal Medicine, American University of Beirut, Beirut, Lebanon
| | - Mazen El Sayed
- Department of Emergency Medicine, American University of Beirut, Beirut, Lebanon
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Li C, Zhang J, Zhu Y. Acute cardiac damage and acute kidney injury associated with hypercalcemia crisis in hyperparathyroidism: a case report. J Int Med Res 2021; 49:3000605211050614. [PMID: 34686090 PMCID: PMC8544773 DOI: 10.1177/03000605211050614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Hyperparathyroidism-induced hypercalcemic crisis is a rare presentation of primary hyperparathyroidism. Primary hyperparathyroidism is caused by uncontrolled and immoderate secretion of parathyroid hormone. The most common presentation in primary hyperparathyroidism is renal stones, soft tissue calcification, cystic bone disease, and even hypercalcemic crisis. We report a patient who presented with multiple organ dysfunction syndrome due to extreme hypercalcemia (serum calcium concentration, 4.79 mmol/L [2.15–2.25 mmol/L]) resulting from primary hyperparathyroidism (serum parathyroid hormone concentration, 2215 pg/mL). The complications in this patient were complete cardiac damage and acute kidney injury. On the basis of the hypercalcemic crisis, the patient subsequently underwent surgical resection of parathyroid adenoma. Two days after surgery, her serum calcium and parathyroid hormone concentrations were normal. The patient had a good recovery after a series of other relevant therapies. In conclusion, surgery should be taken into consideration for hyperparathyroidism.
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Affiliation(s)
- Chunlian Li
- Department of Thyroid and Breast Surgery, Northern Jiangsu People's Hospital and Clinical Medical College of Yangzhou University, Yangzhou, China
| | - Jiaxin Zhang
- Department of Thyroid and Breast Surgery, Northern Jiangsu People's Hospital and Clinical Medical College of Yangzhou University, Yangzhou, China
| | - Yuxiang Zhu
- Department of Thyroid and Breast Surgery, Northern Jiangsu People's Hospital and Clinical Medical College of Yangzhou University, Yangzhou, China
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Khataminia M, Najmeddin F, Najafi A, Sharifnia H, Ahmadi A, Sahebnasagh A, Mojtahedzadeh M. Effect of heart rate control with amiodarone infusion on hemodynamic and clinical outcomes in septic shock patients with tachycardia: a prospective, single-arm clinical study. J Pharm Health Care Sci 2021; 7:37. [PMID: 34629112 PMCID: PMC8504122 DOI: 10.1186/s40780-021-00219-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 08/02/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Keeping the heart rate within the normal range has improved the survival of septic shock patients. Amiodarone could target the underlying pathophysiology of sepsis-induced tachycardia. This study aimed to determine whether amiodarone is effective in controlling the heart rate in critically ill patients with septic shock and sustained tachycardia who were receiving vasopressor. METHODS In this prospective, single-arm cohort study, 46 patients with septic shock and tachycardia were enrolled to receive a loading dose of amiodarone 150 mg, then continuous infusion of 1 mg/min. The primary outcome was the ability of amiodarone in rate control lower than 95 beats per minute (BPM) and maintaining it during 24-h study period. We also recorded the effect of amiodarone on hemodynamic indices as the secondary outcomes. RESULTS The results of the present study indicated a significant decrease in HR in septic shock patients for amiodarone, from 121.0 (116.5, 140.0) at baseline to 91.5(89.3, 108.0) at the end of the study period (p < 0.001). During the study period, a total of 26 (56.52%) of patients achieved the target heart rate lower than 95 BPM and maintained it during study period. Amiodarone decreased HR by 22.8 ± 13.7. While receiving amiodarone infusion, the values for heart rate, mean arterial pressure, cardiac index, norepinephrine infusion rate, and stroke volume index changed significantly between amiodarone initiation and 24-h follow-up (P < 0.001). Amiodarone was well tolerated, because this anti-arrhythmic agent did not increase the need for vasopressor and none of the patients experienced episodes of refractory hypotension. CONCLUSION This study showed that amiodarone infusion successfully reduced the heart rate in sepsis-induced tachycardia. The patients had improved hemodynamic state as indicated by an increase in cardiac index and SVI.
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Affiliation(s)
- Masoud Khataminia
- Student Research Committee, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Farhad Najmeddin
- Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Atabak Najafi
- Department of Anesthesiology and Critical Care Medicine, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamidreza Sharifnia
- Department of Anesthesiology and Critical Care, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Arezoo Ahmadi
- Department of Anesthesiology and Critical Care Medicine, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Adeleh Sahebnasagh
- Department of Internal Medicine, Clinical Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Mojtaba Mojtahedzadeh
- Department of Clinical Pharmacy, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.
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Đurašević S, Ružičić A, Lakić I, Tosti T, Đurović S, Glumac S, Pavlović S, Borković-Mitić S, Grigorov I, Stanković S, Jasnić N, Đorđević J, Todorović Z. The Effects of a Meldonium Pre-Treatment on the Course of the Faecal-Induced Sepsis in Rats. Int J Mol Sci 2021; 22:ijms22189698. [PMID: 34575863 PMCID: PMC8464894 DOI: 10.3390/ijms22189698] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 08/29/2021] [Accepted: 09/01/2021] [Indexed: 12/29/2022] Open
Abstract
Sepsis is a life-threatening condition caused by the dysregulated and overwhelming response to infection, accompanied by an exaggerated pro-inflammatory state and lipid metabolism disturbance leading to sequential organ failure. Meldonium is an anti-ischemic and anti-inflammatory agent which negatively interferes with lipid metabolism by shifting energy production from fatty acid oxidation to glycolysis, as a less oxygen-demanding pathway. Thus, we investigated the effects of a four-week meldonium pre-treatment on faecal-induced sepsis in Sprague-Dawley male rats. Surprisingly, under septic conditions, meldonium increased animal mortality rate compared with the meldonium non-treated group. However, analysis of the tissue oxidative status did not provide support for the detrimental effects of meldonium, nor did the analysis of the tissue inflammatory status showing anti-inflammatory, anti-apoptotic, and anti-necrotic effects of meldonium. After performing tissue lipidomic analysis, we concluded that the potential cause of the meldonium harmful effect is to be found in the overall decreased lipid metabolism. The present study underlines the importance of uninterrupted energy production in sepsis, closely drawing attention to the possible harmful effects of lipid-mobilization impairment caused by certain therapeutics. This could lead to the much-needed revision of the existing guidelines in the clinical treatment of sepsis while paving the way for discovering new therapeutic approaches.
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Affiliation(s)
- Siniša Đurašević
- Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia; (A.R.); (I.L.); (N.J.); (J.Đ.)
- Correspondence: ; Tel.: +381-63-367108
| | - Aleksandra Ružičić
- Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia; (A.R.); (I.L.); (N.J.); (J.Đ.)
| | - Iva Lakić
- Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia; (A.R.); (I.L.); (N.J.); (J.Đ.)
| | - Tomislav Tosti
- Faculty of Chemistry, University of Belgrade, 11000 Belgrade, Serbia;
| | - Saša Đurović
- Institute of General and Physical Chemistry, University of Belgrade, 11000 Belgrade, Serbia;
| | - Sofija Glumac
- School of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (S.G.); (Z.T.)
| | - Slađan Pavlović
- Institute for Biological Research “Siniša Stanković”—National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia; (S.P.); (S.B.-M.); (I.G.)
| | - Slavica Borković-Mitić
- Institute for Biological Research “Siniša Stanković”—National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia; (S.P.); (S.B.-M.); (I.G.)
| | - Ilijana Grigorov
- Institute for Biological Research “Siniša Stanković”—National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia; (S.P.); (S.B.-M.); (I.G.)
| | - Sanja Stanković
- Centre for Medical Biochemistry, University Clinical Centre of Serbia, 11000 Belgrade, Serbia;
- Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
| | - Nebojša Jasnić
- Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia; (A.R.); (I.L.); (N.J.); (J.Đ.)
| | - Jelena Đorđević
- Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia; (A.R.); (I.L.); (N.J.); (J.Đ.)
| | - Zoran Todorović
- School of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (S.G.); (Z.T.)
- University Medical Centre “Bežanijska kosa”, University of Belgrade, 11000 Belgrade, Serbia
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Abstract
Septic cardiomyopathy is an increasingly relevant topic in clinical management of septic shock. However, pathophysiological mechanisms and long-term consequences of sepsis-induced myocardial injury are still poorly understood. Herein, new clinical and histological evidence is provided suggesting an association of myocardial edema formation with tissue injury and subsequent remodeling in septic shock patients. This preliminary data supports myocardial edema as a potentially relevant and largely unexplored mechanism of human septic cardiomyopathy.
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Abstract
Sepsis is the life-threatening organ dysfunction caused by a dysregulated host response to infection and is the leading cause of death in intensive care units. Cardiac dysfunction caused by sepsis, usually termed sepsis-induced cardiomyopathy, is common and has long been a subject of interest. In this Review, we explore the definition, epidemiology, diagnosis and pathophysiology of septic cardiomyopathy, with an emphasis on how best to interpret this condition in the clinical context. Advances in diagnostic techniques have increased the sensitivity of detection of myocardial abnormalities but have posed challenges in linking those abnormalities to therapeutic strategies and relevant clinical outcomes. Sophisticated methodologies have elucidated various pathophysiological mechanisms but the extent to which these are adaptive responses is yet to be definitively answered. Although the indications for monitoring and treating septic cardiomyopathy are clinical and directed towards restoring tissue perfusion, a better understanding of the course and implications of septic cardiomyopathy can help to optimize interventions and improve clinical outcomes.
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Abstract
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The heart is one of the most important oxygen delivery organs, and dysfunction significantly increases the mortality of the body. Hence, the heart has been studied in sepsis for over half a century. However, the definition of sepsis-induced cardiomyopathy is not unified yet, and the conventional conception seems outdated: left ventricular systolic dysfunction (LVSD) along with enlargement of the left ventricle, recovering in 7 to 10 days. With the application of echocardiography in intensive care units, not only LVSD but also left ventricular diastolic dysfunction, right ventricular dysfunction, and even diffuse ventricular dysfunction have been seen. The recognition of sepsis-induced cardiomyopathy is gradually becoming complete, although our understanding of it is not deep, which has made the diagnosis and treatment stagnate. In this review, we summarize the research on sepsis-induced cardiomyopathy. Women and young people with septic cardiomyopathy are more likely to have LVSD, which may have the same mechanism as stress cardiomyopathy. Elderly people with ischemic cardiomyopathy and hypertension tend to have left ventricular diastolic dysfunction. Patients with mechanical ventilation, acute respiratory distress syndrome or other complications of increased right ventricular afterload mostly have right ventricular dysfunction. Diffuse cardiac dysfunction has also been shown in some studies; patients with mixed or co-existing cardiac dysfunction are more common, theoretically. Thus, understanding the pathophysiology of sepsis-induced cardiomyopathy from the perspective of critical care echocardiography is essential.
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Tan K, Harazim M, Simpson A, Tan YC, Gunawan G, Robledo KP, Whitehead C, Tang B, Mclean A, Nalos M. Association Between Premorbid Beta-Blocker Exposure and Sepsis Outcomes-The Beta-Blockers in European and Australian/American Septic Patients (BEAST) Study. Crit Care Med 2021; 49:1493-1503. [PMID: 33938711 DOI: 10.1097/ccm.0000000000005034] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVES To examine the effect of premorbid β-blocker exposure on mortality and organ dysfunction in sepsis. DESIGN Retrospective observational study. SETTING ICUs in Australia, the Czech Republic, and the United States. PATIENTS Total of 4,086 critical care patients above 18 years old with sepsis between January 2014 and December 2018. INTERVENTION Premorbid beta-blocker exposure. MEASUREMENTS AND MAIN RESULTS One thousand five hundred fifty-six patients (38%) with premorbid β-blocker exposure were identified. Overall ICU mortality rate was 15.1%. In adjusted models, premorbid β-blocker exposure was associated with decreased ICU (adjusted odds ratio, 0.80; 95% CI, 0.66-0.97; p = 0.025) and hospital (adjusted odds ratio, 0.83; 95% CI, 0.71-0.99; p = 0.033) mortality. The risk reduction in ICU mortality of 16% was significant (hazard ratio, 0.84, 95% CI, 0.71-0.99; p = 0.037). In particular, exposure to noncardioselective β-blocker before septic episode was associated with decreased mortality. Sequential Organ Failure Assessment score analysis showed that premorbid β-blocker exposure had potential benefits in reducing respiratory and neurologic dysfunction. CONCLUSIONS This study suggests that β-blocker exposure prior to sepsis, especially to noncardioselective β blockers, may be associated with better outcome. The findings suggest prospective evaluation of β-blocker use in the management of sepsis.
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Affiliation(s)
- Kaiquan Tan
- 1 Nepean Clinical School, Sydney Medical School, University of Sydney, Sydney, NSW, Australia. 2 Medical Intensive Care Unit, University Hospital and Biomedicine Centre, Pilsen, Charles University Prague, Czech Republic. 3 Department of Intensive Care Medicine, Nepean Hospital, Kingswood, NSW, Australia. 4 Department of Computer Science, Yale University, New Haven, CT. 5 Medistra Hospital, Jakarta, Indonesia. 6 NHMRC Clinical Trials Centre, The University of Sydney, Sydney, NSW, Australia. 7 Centre for immunology and allergy research, Westmead Millennium Institute, Westmead, NSW, Australia
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Pralidoxime improves the hemodynamics and survival of rats with peritonitis-induced sepsis. PLoS One 2021; 16:e0249794. [PMID: 33822820 PMCID: PMC8023460 DOI: 10.1371/journal.pone.0249794] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 03/22/2021] [Indexed: 12/29/2022] Open
Abstract
Several studies have suggested that sympathetic overstimulation causes deleterious effects in septic shock. A previous study suggested that pralidoxime exerted a pressor effect through a mechanism unrelated to the sympathetic nervous system; this effect was buffered by the vasodepressor action of pralidoxime mediated through sympathoinhibition. In this study, we explored the effects of pralidoxime on hemodynamics and survival in rats with peritonitis-induced sepsis. This study consisted of two sub-studies: survival and hemodynamic studies. In the survival study, 66 rats, which survived for 10 hours after cecal ligation and puncture (CLP), randomly received saline placebo, pralidoxime, or norepinephrine treatment and were monitored for up to 24 hours. In the hemodynamic study, 44 rats were randomly assigned to sham, CLP-saline placebo, CLP-pralidoxime, or CLP-norepinephrine groups, and hemodynamic measurements were performed using a conductance catheter placed in the left ventricle. In the survival study, 6 (27.2%), 15 (68.1%), and 5 (22.7%) animals survived the entire 24-hour monitoring period in the saline, pralidoxime, and norepinephrine groups, respectively (log-rank test P = 0.006). In the hemodynamic study, pralidoxime but not norepinephrine increased end-diastolic volume (P <0.001), stroke volume (P = 0.002), cardiac output (P = 0.003), mean arterial pressure (P = 0.041), and stroke work (P <0.001). The pressor effect of norepinephrine was short-lived, such that by 60 minutes after the initiation of norepinephrine infusion, it no longer had any significant effect on mean arterial pressure. In addition, norepinephrine significantly increased heart rate (P <0.001) and the ratio of arterial elastance to ventricular end-systolic elastance (P = 0.010), but pralidoxime did not. In conclusion, pralidoxime improved the hemodynamics and 24-hour survival rate in rats with peritonitis-induced sepsis, but norepinephrine did not.
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Scheeren TWL, Bakker J, Kaufmann T, Annane D, Asfar P, Boerma EC, Cecconi M, Chew MS, Cholley B, Cronhjort M, De Backer D, Dubin A, Dünser MW, Duranteau J, Gordon AC, Hajjar LA, Hamzaoui O, Hernandez G, Kanoore Edul V, Koster G, Landoni G, Leone M, Levy B, Martin C, Mebazaa A, Monnet X, Morelli A, Payen D, Pearse RM, Pinsky MR, Radermacher P, Reuter DA, Sakr Y, Sander M, Saugel B, Singer M, Squara P, Vieillard-Baron A, Vignon P, Vincent JL, van der Horst ICC, Vistisen ST, Teboul JL. Current use of inotropes in circulatory shock. Ann Intensive Care 2021; 11:21. [PMID: 33512597 PMCID: PMC7846624 DOI: 10.1186/s13613-021-00806-8] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Accepted: 01/09/2021] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Treatment decisions on critically ill patients with circulatory shock lack consensus. In an international survey, we aimed to evaluate the indications, current practice, and therapeutic goals of inotrope therapy in the treatment of patients with circulatory shock. METHODS From November 2016 to April 2017, an anonymous web-based survey on the use of cardiovascular drugs was accessible to members of the European Society of Intensive Care Medicine (ESICM). A total of 14 questions focused on the profile of respondents, the triggering factors, first-line choice, dosing, timing, targets, additional treatment strategy, and suggested effect of inotropes. In addition, a group of 42 international ESICM experts was asked to formulate recommendations for the use of inotropes based on 11 questions. RESULTS A total of 839 physicians from 82 countries responded. Dobutamine was the first-line inotrope in critically ill patients with acute heart failure for 84% of respondents. Two-thirds of respondents (66%) stated to use inotropes when there were persistent clinical signs of hypoperfusion or persistent hyperlactatemia despite a supposed adequate use of fluids and vasopressors, with (44%) or without (22%) the context of low left ventricular ejection fraction. Nearly half (44%) of respondents stated an adequate cardiac output as target for inotropic treatment. The experts agreed on 11 strong recommendations, all of which were based on excellent (> 90%) or good (81-90%) agreement. Recommendations include the indications for inotropes (septic and cardiogenic shock), the choice of drugs (dobutamine, not dopamine), the triggers (low cardiac output and clinical signs of hypoperfusion) and targets (adequate cardiac output) and stopping criteria (adverse effects and clinical improvement). CONCLUSION Inotrope use in critically ill patients is quite heterogeneous as self-reported by individual caregivers. Eleven strong recommendations on the indications, choice, triggers and targets for the use of inotropes are given by international experts. Future studies should focus on consistent indications for inotrope use and implementation into a guideline for circulatory shock that encompasses individualized targets and outcomes.
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Affiliation(s)
- Thomas W. L. Scheeren
- Department of Anesthesiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, P.O.Box 30.001, 9700 RB Groningen, The Netherlands
| | - Jan Bakker
- New York University Medical Center, New York, USA
- Columbia University Medical Center, New York, USA
- Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
- Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Thomas Kaufmann
- Department of Anesthesiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, P.O.Box 30.001, 9700 RB Groningen, The Netherlands
| | - Djillali Annane
- School of Medicine Simone Veil, Raymond Poincaré Hospital (APHP), Department of Intensive Care Medicine, University of Versailles- University Paris Saclay, Garches, France
| | - Pierre Asfar
- Département de Médecine Intensive-Réanimation Et de Médecine Hyperbare, Centre Hospitalier Universitaire Angers; and Institut MITOVASC, CNRS UMR 6215, INSERM U1083, Angers University, Angers, France
| | - E. Christiaan Boerma
- Medical Centre Leeuwarden, Department of Intensive Care, Leeuwarden, the Netherlands
| | - Maurizio Cecconi
- Department of Anesthesia and Intensive Care, IRCCS Humanitas Research Hospital, Via Manzoni 56, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini, Milan, Italy
| | - Michelle S. Chew
- Department of Anaesthesiology and Intensive Care, Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Bernard Cholley
- Department of Anaesthesiology & Intensive Care Medicine, AP-HP, Hôpital Européen Georges Pompidou, Paris, France
- Université de Paris, Paris, France
| | - Maria Cronhjort
- Section of Anaesthesiology and Intensive Care, Department of Clinical Science and Education, Karolinska Institutet, Södersjukhuset, Stockholm, Sweden
| | - Daniel De Backer
- Department of Intensive Care, CHIREC Hospitals, Université Libre de Bruxelles, Brussels, Belgium
| | - Arnaldo Dubin
- Cátedra de Farmacología Aplicada, Facultad de Ciencias Médicas, Universidad Nacional de La Plata Y Servicio de Terapia Intensiva, Sanatorio Otamendi, Buenos Aires, Argentina
| | - Martin W. Dünser
- Department of Anesthesiology and Intensive Care Medicine, Kepler University Hospital and Johannes Kepler University Linz, Linz, Austria
| | - Jacques Duranteau
- Department of Anaesthesia and Intensive Care, Assistance Publique Des Hopitaux de Paris, Hôpitaux Universitaires Paris-Saclay, Université Paris-Saclay, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France
| | - Anthony C. Gordon
- Division of Anaesthetics, Pain Medicine and Intensive Care, Imperial College London, London, UK
| | - Ludhmila A. Hajjar
- Department of Cardiopneumology, Instituto Do Coracao, Universidade de São Paulo, Hospital SirioLibanes, São Paulo, Brazil
| | - Olfa Hamzaoui
- Assistance Publique-Hôpitaux de Paris, Paris Saclay University Hospitals, Antoine Béclère Hospital, Paris, France
| | - Glenn Hernandez
- Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | | | - Geert Koster
- Department of Critical Care, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Giovanni Landoni
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - Marc Leone
- Aix Marseille Université, Assistance Publique Hôpitaux de Marseille, Service D’Anesthésie Et de Réanimation CHU Nord, Marseille, France
| | - Bruno Levy
- Service de Réanimation Médicale Brabois Et Pôle Cardio-Médico-Chirurgical. CHRU Brabois, INSERM U1116, Université de Lorraine, Vandoeuvre les NancyNancy, 54500 France
| | - Claude Martin
- Aix Marseille Université, Assistance Publique Hôpitaux de Marseille, Service D’Anesthésie Et de Réanimation CHU Nord, Marseille, France
| | - Alexandre Mebazaa
- Department of Anesthesia, Burn and Critical Care, APHP Hôpitaux Universitaires Saint Louis LariboisièreUniversité Paris DiderotU942 Inserm, Paris, France
| | - Xavier Monnet
- Medical Intensive Care Unit, Assistance Publique-Hôpitaux de Paris, Paris-Saclay University Hospitals, Bicêtre hospital, Le Kremlin-Bicêtre, France
- INSERM UMR_S 999, FHU SEPSIS, Le Kremlin-Bicêtre, France
| | - Andrea Morelli
- Department of Clinical Internal, Anesthesiological and Cardiovascular Science, Sapienza University of Rome, Rome, Italy
| | - Didier Payen
- University Paris 7 Denis Diderot; INSERM 1160 and Hôpital Lariboisière, APHP, Paris, France
| | - Rupert M. Pearse
- William Harvey Research Institute, Queen Mary University of London, London, EC1M 6BQ UK
| | - Michael R. Pinsky
- Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, USA
| | - Peter Radermacher
- Institut Für Anästhesiologische Pathophysiologie Und Verfahrensentwicklung, Universitätsklinikum Ulm, Ulm, Germany
| | - Daniel A. Reuter
- Department of Anesthesiology and Intensive Care Medicine, Rostock University Medical Centre, Rostock, Germany
| | - Yasser Sakr
- Department of Anesthesiology and Intensive Care, Uniklinikum Jena, Jena, Germany
| | - Michael Sander
- Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Giessen, UKGM, Justus-Liebig University Giessen, Giessen, Germany
| | - Bernd Saugel
- Department of Anesthesiology, Center of Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Mervyn Singer
- Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, London, UK
| | - Pierre Squara
- ICU Department, Réanimation CERIC, Clinique Ambroise Paré, Neuilly, France
| | - Antoine Vieillard-Baron
- Assistance Publique-Hôpitaux de Paris, University Hospital Ambroise Paré, intensive care unit, Boulogne-Billancourt, France
- INSERM U-1018, CESP, Team 5, University of Versailles Saint-Quentin en Yvelines, Villejuif, France
| | - Philippe Vignon
- Medical-Surgical Intensive Care Unit, INSERM CIC-1435, Teaching Hospital of Limoges, Limoges, France
- University of Limoges, Limoges, France
| | - Jean-Louis Vincent
- Université Libre de Bruxelles - Dept of Intensive Care, Erasme Univ Hospital, Brussels, Belgium
| | - Iwan C. C. van der Horst
- Department of Intensive Care Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Simon T. Vistisen
- Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Anesthesia and Intensive Care, Aarhus University Hospital, Aarhus, Denmark
| | - Jean-Louis Teboul
- Medical Intensive Care Unit, Assistance Publique-Hôpitaux de Paris, Paris-Saclay University Hospitals, Bicêtre hospital, Le Kremlin-Bicêtre, France
- INSERM UMR_S 999, FHU SEPSIS, Le Kremlin-Bicêtre, France
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Roshdy A, Zaher S, Fayed H, Coghlan JG. COVID-19 and the Heart: A Systematic Review of Cardiac Autopsies. Front Cardiovasc Med 2021; 7:626975. [PMID: 33585586 PMCID: PMC7876291 DOI: 10.3389/fcvm.2020.626975] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Accepted: 12/17/2020] [Indexed: 01/06/2023] Open
Abstract
Importance: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated cardiac injury has been postulated secondary to several mechanisms. While tissue diagnosis is limited during the acute illness, postmortem studies can help boost our understanding and guide management. Objective: To report the cardiac tissue autopsy findings in coronavirus disease 2019 (COVID-19) decedents. Evidence Review: Articles published in PubMed and Embase reporting postmortem cardiac pathology of COVID-19 decedents till September 2020. We included adult studies excluding preprints. The Joanna Briggs Institute Critical Appraisal Checklist for Case Reports was used to assess quality. We extracted gross and histology data as well as the incidence of myocarditis, cardiac ischemia, thrombosis, and dilatation. We also looked at the reported cause of death (PROSPERO registration CRD42020190898). Findings: Forty-one relevant studies identified including 316 cases. The deceased were mostly male (62%) and elderly (median age, 75; range, 22-97 years). The most common comorbidities were hypertension (48%) and coronary artery disease (33%). Cardiac pathologies contributed to the death of 15 cases. Besides chronic cardiac pathologies, postmortem examination demonstrated cardiac dilatation (20%), acute ischemia (8%), intracardiac thrombi (2.5%), pericardial effusion (2.5%), and myocarditis (1.5%). SARS-CoV-2 was detected within the myocardium of 47% of studied hearts. Conclusions and Relevance: SARS-CoV-2 can invade the heart, but a minority of cases were found to have myocarditis. Cardiac dilatation, ischemia, mural, and microthrombi were the most frequent findings. The systematic review was limited by the small number of cases and the quality of the studies, and there is a need to standardize the cardiac postmortem protocols.
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Affiliation(s)
- Ashraf Roshdy
- Critical Care Unit, Whipps Cross University Hospital, Barts Health NHS Trust, London, United Kingdom.,Critical Care Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Shroque Zaher
- Department of Pathology, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
| | - Hossam Fayed
- National Pulmonary Hypertension Unit-Cardiology Department, Royal Free Hospital, London, United Kingdom.,Institute of Cardiovascular Science, UCL, London, United Kingdom
| | - John Gerry Coghlan
- National Pulmonary Hypertension Unit-Cardiology Department, Royal Free Hospital, London, United Kingdom
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Argirò A, Olivotto I. The coronary microcirculation in sepsis: not of micro-importance. Glob Cardiol Sci Pract 2020; 2020:e202030. [PMID: 33598490 PMCID: PMC7868102 DOI: 10.21542/gcsp.2020.30] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Affiliation(s)
- Alessia Argirò
- Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy
| | - Iacopo Olivotto
- Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy
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30
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Lachmet-Thebaud L, Marchandot B, Matsushita K, Sato C, Dagrenat C, Greciano S, De Poli F, Leddet P, Peillex M, Hess S, Carmona A, Jimenez C, Heger J, Reydel A, Ohlmann P, Jesel L, Morel O. Impact of residual inflammation on myocardial recovery and cardiovascular outcome in Takotsubo patients. ESC Heart Fail 2020; 8:259-269. [PMID: 33207039 PMCID: PMC7835625 DOI: 10.1002/ehf2.12945] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 07/15/2020] [Accepted: 07/19/2020] [Indexed: 12/13/2022] Open
Abstract
Aims Recent insights have emphasized the importance of myocardial and systemic inflammation in Takotsubo syndrome (TTS). In a large registry of unselected patients, we sought to evaluate whether residual high inflammatory response (RHIR) could impact cardiovascular outcome after TTS. Methods and results Patients with TTS were retrospectively included between 2008 and 2018 in three general hospitals. Three hundred eighty‐five patients with TTS were split into three subgroups, according to tertiles of C‐reactive protein (CRP) levels at discharge (CRP <5.2 mg/L, CRP range 5.2 to 19 mg/L, and CRP >19 mg/L). The primary endpoint was the impact of RHIR, defined as CRP >19 mg/L at discharge, on cardiac death or hospitalization for heart failure. Follow up was obtained in 382 patients (99%) after a median of 747 days. RHIR patients were more likely to have a history of cancer or a physical trigger. Left ventricular ejection fraction (LVEF) at admission and at discharge were comparable between groups. By contrast, RHIR was associated with lower LVEF at follow up (61.7% vs. 60.7% vs. 57.9%; P = 0.004) and increased cardiac late mortality (0% vs. 0% vs. 10%; P = 0.001). By multivariate Cox regression analysis, RHIR was an independent predictor of cardiac death or hospitalization for heart failure (hazard ratio: 1.87; 95% confidence interval: 1.08 to 3.25; P = 0.025). Conclusions Residual high inflammatory response was associated with impaired LVEF at follow up and was evidenced as an independent factor of cardiovascular events. All together, these findings underline RHIR patients as a high‐risk subgroup, to target in future clinical trials with specific therapies to attenuate RHIR.
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Affiliation(s)
- Lucie Lachmet-Thebaud
- Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Université de Strasbourg, BP 426, Strasbourg, 67091, France
| | - Benjamin Marchandot
- Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Université de Strasbourg, BP 426, Strasbourg, 67091, France
| | - Kensuke Matsushita
- Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Université de Strasbourg, BP 426, Strasbourg, 67091, France.,UMR INSERM 1260 Regenerative Nanomedicine, Université de Strasbourg, Strasbourg, France
| | - Chisato Sato
- Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Université de Strasbourg, BP 426, Strasbourg, 67091, France.,Department of Cardiovascular Center, Showa University Koto-Toyosu Hospital, Tokyo, Japan
| | - Charlotte Dagrenat
- Pole d'activité cardiovasculaire, Centre Hospitalier de Haguenau, Haguenau, France
| | - Stephane Greciano
- Pole d'activité cardiovasculaire, Hôpitaux Civils de Colmar, Colmar, France
| | - Fabien De Poli
- Pole d'activité cardiovasculaire, Centre Hospitalier de Haguenau, Haguenau, France
| | - Pierre Leddet
- Pole d'activité cardiovasculaire, Centre Hospitalier de Haguenau, Haguenau, France
| | - Marilou Peillex
- Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Université de Strasbourg, BP 426, Strasbourg, 67091, France
| | - Sébastien Hess
- Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Université de Strasbourg, BP 426, Strasbourg, 67091, France
| | - Adrien Carmona
- Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Université de Strasbourg, BP 426, Strasbourg, 67091, France
| | - Charline Jimenez
- Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Université de Strasbourg, BP 426, Strasbourg, 67091, France
| | - Joe Heger
- Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Université de Strasbourg, BP 426, Strasbourg, 67091, France
| | - Antje Reydel
- Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Université de Strasbourg, BP 426, Strasbourg, 67091, France
| | - Patrick Ohlmann
- Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Université de Strasbourg, BP 426, Strasbourg, 67091, France
| | - Laurence Jesel
- Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Université de Strasbourg, BP 426, Strasbourg, 67091, France.,UMR INSERM 1260 Regenerative Nanomedicine, Université de Strasbourg, Strasbourg, France
| | - Olivier Morel
- Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Université de Strasbourg, BP 426, Strasbourg, 67091, France.,UMR INSERM 1260 Regenerative Nanomedicine, Université de Strasbourg, Strasbourg, France
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Y-Hassan S. Autonomic neurocardiogenic syndrome is stonewalled by the universal definition of myocardial infarction. World J Cardiol 2020; 12:231-247. [PMID: 32774776 PMCID: PMC7383352 DOI: 10.4330/wjc.v12.i6.231] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 04/27/2020] [Accepted: 05/14/2020] [Indexed: 02/06/2023] Open
Abstract
Myocardial infarction (MI) is defined as myocardial cell death due to prolonged myocardial ischemia. Clinically, troponin rise and/or fall have become the “defining feature of MI” according to the universal definition of MI (UD-MI). Takotsubo syndrome (TS) and TS-related disease conditions also cause troponin elevation with typical rise and/or fall pattern but through a mechanism other than coronary ischemia. By strict application of the clinical diagnostic criteria for type-1 MI, type-2 MI, type-3 MI, and MI with non-obstructive coronary arteries according to the UD-MI including the fourth one published recently, TS and most of the 26 other causes of troponin elevation mentioned in the fourth UD-MI may erroneously be classified as MI. The existing evidence argues for the case that TS by itself is not a MI. Hyper-activation of the autonomic-sympathetic nervous system including local cardiac sympathetic hyper-activation and disruption with nor-epinephrine churn and spillover is the most probable cause of TS. This autonomic neuro-cardiogenic (ANCA) mechanism results in myocardial “cramp” (stunning), the severity and duration of which depend on the degree of the sympathetic-hyperactivation and nor-epinephrine spillover. The myocardial cramp may squeeze the cytosolic free troponin pools causing mild to moderate troponin elevation in TS and TS-related disease conditions. This ANCA syndrome, which has hitherto been enveloped by the UD-MI over more than one decade, may occur in acute, recurrent, and chronic forms. In this critical review, the controversies of UD-MI, evidence for ANCA syndrome, and a hypothetical mechanism for the troponin elevation in ANCA syndrome are provided.
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Affiliation(s)
- Shams Y-Hassan
- Coronary Artery Disease Area, Heart and Vascular Theme, Karolinska Institutet and Karolinska University Hospital, Stockholm S-141 86, Sweden
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Domizi R, Calcinaro S, Harris S, Beilstein C, Boerma C, Chiche JD, D'Egidio A, Damiani E, Donati A, Koetsier PM, Madden MP, McAuley DF, Morelli A, Pelaia P, Royer P, Shankar-Hari M, Wickboldt N, Zolfaghari P, Singer M. Relationship between norepinephrine dose, tachycardia and outcome in septic shock: A multicentre evaluation. J Crit Care 2020; 57:185-190. [DOI: 10.1016/j.jcrc.2020.02.014] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 02/04/2020] [Accepted: 02/21/2020] [Indexed: 01/07/2023]
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Lachmet-Thébaud L, Marchandot B, Matsushita K, Dagrenat C, Peillex M, Sato C, Trimaille A, Reydel A, Trinh A, Ohlmann P, Jesel L, Morel O. Systemic Inflammatory Response Syndrome Is a Major Determinant of Cardiovascular Outcome in Takotsubo Syndrome. Circ J 2020; 84:592-600. [PMID: 32147633 DOI: 10.1253/circj.cj-19-1088] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/01/2024]
Abstract
BACKGROUND Recent insights have emphasized the importance of inflammatory response in takotsubo syndrome (TTS). We sought to evaluate the predictors of systemic inflammatory response syndrome (SIRS) and its impact on cardiovascular mortality after TTS. METHODS AND RESULTS The 215 TTS patients were retrospectively included between September 2008 and January 2018. SIRS was diagnosed in 96 patients (44.7%). They had lower left ventricular ejection fraction (LVEF) on admission (34.5% vs. 41.9%; P<0.001) and higher peak brain natriuretic peptide and troponin. At a median follow-up of 518 days, SIRS was associated with increased in-hospital mortality (14.6% vs. 5.0%; P=0.019), overall mortality (29.4% vs. 10.8%; P=0.002), and cardiovascular mortality (10.6% vs. 2.1%; P=0.026). A history of cancer (OR, 3.36; 95% CI: 1.54-7.31; P=0.002) and LVEF <40% at admission (OR, 2.31; 95% CI: 1.16-4.58; P=0.017) were identified as independent predictors of SIRS. On multivariate Cox regression analysis, SIRS (HR, 12.8; 95% CI: 1.58-104; P=0.017), age (HR, 1.09; 95% CI: 1.02-1.16; P=0.01), and LVEF <40% at discharge (HR, 9.88; 95% CI: 2.54-38.4; P=0.001) were independent predictors of cardiovascular death. CONCLUSIONS SIRS was found in a large proportion of TTS patients and was associated with enhanced myocardial damage and adverse outcome in the acute phase. At long-term follow-up, SIRS remained an independent factor of cardiovascular death.
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Affiliation(s)
| | - Benjamin Marchandot
- Department of Cardiology, Nouvel Hopital Civil, University Hospital of Strasbourg
| | - Kensuke Matsushita
- Department of Cardiology, Nouvel Hopital Civil, University Hospital of Strasbourg
- UMR 1260 INSERM Regenerative Nanomedicine, University of Strasbourg
| | - Charlotte Dagrenat
- Department of Cardiology, Nouvel Hopital Civil, University Hospital of Strasbourg
| | - Marilou Peillex
- Department of Cardiology, Nouvel Hopital Civil, University Hospital of Strasbourg
| | - Chisato Sato
- Department of Cardiology, Nouvel Hopital Civil, University Hospital of Strasbourg
- Department of Cardiovascular Center, Showa University Koto-Toyosu Hospital
| | - Antonin Trimaille
- Department of Cardiology, Nouvel Hopital Civil, University Hospital of Strasbourg
| | - Antje Reydel
- Department of Cardiology, Nouvel Hopital Civil, University Hospital of Strasbourg
| | - Annie Trinh
- Department of Cardiology, Nouvel Hopital Civil, University Hospital of Strasbourg
| | - Patrick Ohlmann
- Department of Cardiology, Nouvel Hopital Civil, University Hospital of Strasbourg
| | - Laurence Jesel
- Department of Cardiology, Nouvel Hopital Civil, University Hospital of Strasbourg
- UMR 1260 INSERM Regenerative Nanomedicine, University of Strasbourg
| | - Olivier Morel
- Department of Cardiology, Nouvel Hopital Civil, University Hospital of Strasbourg
- UMR 1260 INSERM Regenerative Nanomedicine, University of Strasbourg
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Prognosis of β-adrenergic blockade therapy on septic shock and sepsis: A systematic review and meta-analysis of randomized controlled studies. Cytokine 2019; 126:154916. [PMID: 31756644 DOI: 10.1016/j.cyto.2019.154916] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Revised: 10/21/2019] [Accepted: 10/31/2019] [Indexed: 12/17/2022]
Abstract
PURPOSE β-adrenoceptor antagonist (β-blocker) may have potential in the treatment of septic shock and sepsis. However, the relevant research findings are still controversial. METHODS We conducted a systematic review and meta-analysis to explore the efficacy of β-blocker in patients with septic shock and sepsis. The primary sources of the reviewed studies through August 2018, with restriction on the language of English, were Pubmed and Embase. Randomized controlled trials (RCT) were included to evaluate the efficacy of β-blocker in the treatment of septic shock and sepsis. Meta analysis was performed using a random effect model. Two researchers independently searched articles, extracted data, and assessed the quality of the included studies. RESULTS A total of 6 studies related to 5 original RCTs were qualified for inclusion in this systematic review and meta-analysis with a total of 363 patients with sepsis and/or septic shock. β-blocker was associated with a significantly decreased 28-day mortality compared to usual treatment group as the control (RR = 0.59, 95%CI: 0.48, 0.74; P < 0.00001). Heart rate in β-blocker was significantly lower than that in the standard care group (SMD = -2.01, 95%CI: -3.03, -0.98; P = 0001). CONCLUSION β-blocker of esmolol is safe and effective in improving 28-day mortality and controlling ventricular rate in patients with sepsis after fluid resuscitation, and has no significant adverse effect on tissue perfusion.
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Roul D, Rozec B, Ferron M, Erfanian M, Persello A, Audigane L, Grabherr A, Erraud A, Merlet N, Guijarro D, Muramatsu I, Lauzier B, Gauthier C. β 1-Adrenergic cardiac contractility is increased during early endotoxemic shock: Involvement of cyclooxygenases. Life Sci 2019; 236:116865. [PMID: 31525428 DOI: 10.1016/j.lfs.2019.116865] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Revised: 09/06/2019] [Accepted: 09/09/2019] [Indexed: 12/17/2022]
Abstract
AIMS Endothelial dysfunction is one of the earliest symptoms in septic patients and plays an important role in the cardiovascular alterations. However, the endothelial mechanisms involved in the impaired sympathetic regulation of the cardiovascular system are not clear. This study aimed to determine the role of the endocardial endothelium (EE) in the cardiac β-adrenergic (β-AR) remodeling at the early phase of endotoxemic shock. MAIN METHODS Rats received either lipopolysaccharide (LPS) or saline (control) intravenously. Three hours later, β-AR cardiac contractility was evaluated on papillary muscles with or without a functional EE. KEY FINDINGS Isoproterenol-induced contractility was strongly increased in papillary muscles from LPS rats. A similar increase was observed with a β1-AR stimulation, whereas β2-AR and β3-AR produced similar contractility in control and LPS treatments. The removal of the EE did not modify β1-AR-induced contractility in controls, whereas it abolished the increased β1-AR response in LPS-treated muscles. In LPS-treated papillary muscle, the increased β1-AR-induced contractility was not modified by pretreatment with a NOS inhibitor or an endothelin receptor antagonist. Conversely, the increased β1-AR-induced contractility was abolished by indomethacin, a non-selective cyclooxygenase (COX) inhibitor, as well as by selective inhibitors of COX1 and COX2. An early treatment with indomethacin improved the survival of LPS rat. SIGNIFICANCE Our results suggest that the EE is involved in the increased cardiac β1-AR contractility in the early phase of endotoxemic shock. This effect is mediated through the activation of COX1 and COX2 and suggests these may be novel putative therapeutic targets during endotoxemic shock.
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Affiliation(s)
- David Roul
- l'institut du thorax, INSERM, CNRS, UNIV Nantes, Nantes, France
| | - Bertrand Rozec
- l'institut du thorax, INSERM, CNRS, UNIV Nantes, CHU Nantes, Nantes, France.
| | - Marine Ferron
- l'institut du thorax, INSERM, CNRS, UNIV Nantes, Nantes, France
| | | | | | - Leslie Audigane
- l'institut du thorax, INSERM, CNRS, UNIV Nantes, Nantes, France
| | | | | | - Nolwenn Merlet
- l'institut du thorax, INSERM, CNRS, UNIV Nantes, Nantes, France
| | - Damien Guijarro
- l'institut du thorax, INSERM, CNRS, UNIV Nantes, CHU Nantes, Nantes, France
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Maiese A, Manetti F, La Russa R, Di Fazio N, De Matteis A, Frati P, Fineschi V. Septic myocardial calcification: A case report. J Forensic Leg Med 2019; 65:45-47. [PMID: 31100653 DOI: 10.1016/j.jflm.2019.05.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Revised: 04/30/2019] [Accepted: 05/10/2019] [Indexed: 10/26/2022]
Abstract
The histological findings in the heart in cases of fatal sepsis can show myocytolysis, interstitial fibrosis, necrotic contraction band, mononuclear infiltrates, and interstitial edema, which can be used in post mortem diagnosis of sepsis. Septic myocardial calcification is a very rare condition, and only a few cases have been reported in the literature. In general, the pathogenesis of the myocardial calcification has not been well clarified, but two pathogenic mechanisms have been universally recognized: metastatic or dystrophic. We present a rare case of sepsis-related myocardial calcification. Here we report a case involving a 72-year-old white male who was admitted to a hospital for a polytrauma caused by a motorbike accident. On the 110th day of hospitalization, the patient was diagnosed with a septic process and a subsequent transesophageal echocardiogram revealed the presence of a calcification on the right atrial wall. According to the medical history of the patient there were no systemic factors predisposing to calcium crystals deposition in tissues. Patient died due to multi-organ failure in the course of multimicrobial septic shock during the 149th day. The autopsy revealed both the presence of a greenish-brown formation and a greater consistency of the right atrial wall. The histological investigation of the right atrium wall showed a wide calcification area localized at subendocardial level, which contained fibrin deposition and was surrounded by fibrotic tissue.
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Affiliation(s)
- Aniello Maiese
- Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, Viale Regina Elena 336, 00161, Italy; IRCCS Neuromed, Via Atinense 18, Pozzilli, 86077, Italy
| | - Federico Manetti
- Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, Viale Regina Elena 336, 00161, Italy
| | - Raffaele La Russa
- Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, Viale Regina Elena 336, 00161, Italy; IRCCS Neuromed, Via Atinense 18, Pozzilli, 86077, Italy
| | - Nicola Di Fazio
- Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, Viale Regina Elena 336, 00161, Italy
| | - Alessandra De Matteis
- Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, Viale Regina Elena 336, 00161, Italy
| | - Paola Frati
- Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, Viale Regina Elena 336, 00161, Italy; IRCCS Neuromed, Via Atinense 18, Pozzilli, 86077, Italy
| | - Vittorio Fineschi
- Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, Viale Regina Elena 336, 00161, Italy; IRCCS Neuromed, Via Atinense 18, Pozzilli, 86077, Italy.
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Ndongson-Dongmo B, Lang GP, Mece O, Hechaichi N, Lajqi T, Hoyer D, Brodhun M, Heller R, Wetzker R, Franz M, Levy FO, Bauer R. Reduced ambient temperature exacerbates SIRS-induced cardiac autonomic dysregulation and myocardial dysfunction in mice. Basic Res Cardiol 2019; 114:26. [DOI: 10.1007/s00395-019-0734-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Accepted: 04/12/2019] [Indexed: 12/13/2022]
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38
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Durand M, Louis H, Fritz C, Levy B, Kimmoun A. β-bloquants dans la prise en charge du choc septique. MEDECINE INTENSIVE REANIMATION 2019. [DOI: 10.3166/rea-2019-0095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Les adrénorécepteurs α et en particulier β sont les principales cibles de l’adrénaline et de la noradrénaline libérées par le système sympathique activé. Durant le choc septique, la dysautonomie est une stimulation prolongée à un haut niveau d’intensité du système nerveux sympathique à l’origine d’une altération de la contractilité, de la vasoréactivité et d’une immunodépression. Ainsi, l’administration précoce d’un traitement β-bloquant lors du choc septique pourrait pondérer les effets délétères de cette surstimulation sympathique. Néanmoins, si les preuves expérimentales sont en faveur de cette approche, l’accumulation des preuves cliniques reste encore insuffisante.
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Lesur O, Delile E, Asfar P, Radermacher P. Hemodynamic support in the early phase of septic shock: a review of challenges and unanswered questions. Ann Intensive Care 2018; 8:102. [PMID: 30374729 PMCID: PMC6206320 DOI: 10.1186/s13613-018-0449-8] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Accepted: 10/20/2018] [Indexed: 12/13/2022] Open
Abstract
Background Improving sepsis support is one of the three pillars of a 2017 resolution according to the World Health Organization (WHO). Septic shock is indeed a burden issue in the intensive care units. Hemodynamic stabilization is a cornerstone element in the bundle of supportive treatments recommended in the Surviving Sepsis Campaign (SSC) consecutive biannual reports. Main body The “Pandera’s box” of septic shock hemodynamics is an eternal debate, however, with permanent contentious issues. Fluid resuscitation is a prerequisite intervention for sepsis rescue, but selection, modalities, dosage as well as duration are subject to discussion while too much fluid is associated with worsen outcome, vasopressors often need to be early introduced in addition, and catecholamines have long been recommended first in the management of septic shock. However, not all patients respond positively and controversy surrounding the efficacy-to-safety profile of catecholamines has come out. Preservation of the macrocirculation through a “best” mean arterial pressure target is the actual priority but is still contentious. Microcirculation recruitment is a novel goal to be achieved but is claiming more knowledge and monitoring standardization. Protection of the cardio-renal axis, which is prevalently injured during septic shock, is also an unavoidable objective. Several promising alternative or additive drug supporting avenues are emerging, trending toward catecholamine’s sparing or even “decatecholaminization.” Topics to be specifically addressed in this review are: (1) mean arterial pressure targeting, (2) fluid resuscitation, and (3) hemodynamic drug support. Conclusion Improving assessment and means for rescuing hemodynamics in early septic shock is still a work in progress. Indeed, the bigger the unresolved questions, the lower the quality of evidence.
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Affiliation(s)
- Olivier Lesur
- Division of Intensive Care Units, Department of Medicine, Faculté de Médecine et des Sciences de la Santé, Centre de Recherche du CHUS, Université de Sherbrooke, Sherbrooke, QC, Canada.
| | - Eugénie Delile
- Division of Intensive Care Units, Department of Medicine, Faculté de Médecine et des Sciences de la Santé, Centre de Recherche du CHUS, Université de Sherbrooke, Sherbrooke, QC, Canada
| | - Pierre Asfar
- Département de Médecine Intensive-Réanimation, Centre Hospitalier Universitaire, Université d'Angers, Angers, France
| | - Peter Radermacher
- Institut für Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum, Ulm, Germany
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40
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Short-Term Prognosis of Myocardial Injury, Type 1, and Type 2 Myocardial Infarction in the Emergency Unit. Am J Med 2018; 131:1209-1219. [PMID: 29753793 DOI: 10.1016/j.amjmed.2018.04.032] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2018] [Revised: 04/18/2018] [Accepted: 04/18/2018] [Indexed: 11/23/2022]
Abstract
BACKGROUND Type 2 myocardial infarction and nonischemic myocardial injury, corresponding to troponin elevation without atherothrombosis, are emerging concepts suspected of being common in emergency departments (ED). However, their respective frequencies, risk profiles, and short-term prognoses remain to be investigated. METHODS Among all the patients admitted from January 2014 to December 2016 in a university hospital ED (n = 33,669), those with elevated conventional troponin Ic (≥0.10 µg/L) (n = 4436, 13%) were systematically adjudicated as having type 1 or type 2 myocardial infarction in the presence of symptoms or signs of myocardial ischemia (typical chest pain or electrocardiographic changes) or myocardial injury without such signs. RESULTS Among the 4436 patients included, 1453 (33%) were classified as having myocardial injury, 947 (21%) as having type 2 and 2036 (46%) as having type 1 myocardial infarction. Compared with type 1 patients, patients with type 2 myocardial infarction and myocardial injury were markedly older (respective median ages: 67, 81, and 84 years; P < .001) with more frequent comorbidities. In multivariate analysis, myocardial injury was associated with a lower risk of cardiovascular death (odds ratio 43; 95% confidence interval, 0.29-0.65; P < .001) but a higher risk of all-cause in-hospital death (odds ratio 1.43; 95% confidence interval, 1.02-2.00; P = .037). Systolic blood pressure <90mm Hg and heart rate >100 beats per minute at admission were strongly associated with all-cause mortality, and the troponin rate was associated with cardiovascular mortality in all groups. CONCLUSIONS In a large study of patients with elevated troponins in an ED, myocardial injury and type 2 myocardial infarction were frequent and associated with a worse in-hospital prognosis than type 1 myocardial infarction resulting from noncardiovascular events.
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41
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Ripoll JG, Blackshear JL, Díaz-Gómez JL. Acute Cardiac Complications in Critical Brain Disease. Neurosurg Clin N Am 2018; 29:281-297. [PMID: 29502718 DOI: 10.1016/j.nec.2017.11.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Acute cardiac complications in critical brain disease should be understood as a clinical condition representing an intense brain-heart crosstalk and might mimic ischemic heart disease. Two main entities (neurogenic stunned myocardium [NSM] and stress cardiomyopathy) have been better characterized in the neurocritically ill patients and they portend worse clinical outcomes in these cases. The pathophysiology of NSM remains elusive. However, significant progress has been made on the early identification of neurocardiac compromise following acute critical brain disease. Effective prevention and treatment interventions are yet to be determined.
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Affiliation(s)
- Juan G Ripoll
- Department of Critical Care Medicine, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA
| | - Joseph L Blackshear
- Department of Cardiology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA
| | - José L Díaz-Gómez
- Departments of Critical Care Medicine, Anesthesiology and Neurologic Surgery, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
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Sanfilippo F, Corredor C, Fletcher N, Tritapepe L, Lorini FL, Arcadipane A, Vieillard-Baron A, Cecconi M. Left ventricular systolic function evaluated by strain echocardiography and relationship with mortality in patients with severe sepsis or septic shock: a systematic review and meta-analysis. Crit Care 2018; 22:183. [PMID: 30075792 PMCID: PMC6091069 DOI: 10.1186/s13054-018-2113-y] [Citation(s) in RCA: 117] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Accepted: 07/03/2018] [Indexed: 01/25/2023] Open
Abstract
BACKGROUND Sepsis-induced myocardial dysfunction is associated with poor outcomes, but traditional measurements of systolic function such as left ventricular ejection fraction (LVEF) do not directly correlate with prognosis. Global longitudinal strain (GLS) utilizing speckle-tracking echocardiography (STE) could be a better marker of intrinsic left ventricular (LV) function, reflecting myocardial deformation rather than displacement and volume changes. We sought to investigate the prognostic value of GLS in patients with sepsis and/or septic shock. METHODS We conducted a systematic review (PubMed and Embase up to 26 October 2017) and meta-analysis to investigate the association between GLS and mortality at longest follow up in patients with severe sepsis and/or septic shock. In the primary analysis, we included studies reporting transthoracic echocardiography data on GLS according to mortality. A secondary analysis evaluated the association between LVEF and mortality including data from studies reporting GLS. RESULTS We included eight studies in the primary analysis with a total of 794 patients (survival 68%, n = 540). We found a significant association between worse LV function and GLS values and mortality: standard mean difference (SMD) - 0.26; 95% confidence interval (CI) - 0.47, - 0.04; p = 0.02 (low heterogeneity, I2 = 43%). No significant association was found between LVEF and mortality in the same population of patients (eight studies; SMD, 0.02; 95% CI - 0.14, 0.17; p = 0.83; no heterogeneity, I2 = 3%). CONCLUSIONS Worse GLS (less negative) values are associated with higher mortality in patients with severe sepsis or septic shock, while such association is not valid for LVEF. More critical care research is warranted to confirm the better ability of STE in demonstrating underlying intrinsic myocardial disease compared to LVEF.
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Affiliation(s)
- F. Sanfilippo
- Department of Anaesthesia and Intensive Care, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), Via Tricomi 5, 90127 Palermo, Italy
| | - C. Corredor
- Department of Perioperative Medicine, Bart’s Heart Centre St. Bartholomew’s Hospital, W. Smithfield, London, UK
| | - N. Fletcher
- Department of Anaesthesia and Critical Care, St Georges University Hospitals NHS Trust, Blackshaw Road, London, SW170QT UK
| | - L. Tritapepe
- Department of Cardiovascular, Respiratory, Nephrological, Anaesthetic and Geriatric Sciences, Sapienza University of Rome, Rome, Italy
| | - F. L. Lorini
- Department of Anaesthesia and Intensive Care, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - A. Arcadipane
- Department of Anaesthesia and Intensive Care, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), Via Tricomi 5, 90127 Palermo, Italy
| | - A. Vieillard-Baron
- Assistance Publique-Hopitaux de Paris, University Hospital Ambroise Paré, Intensive Care Unit, Section Thorax-Vascular Disease-Abdomen-Metabolism, 92100 Boulogne-Billancourt, France
- INSERM U-1018, CESP, Team 5 (EpReC, Renal and Cardiovascular Epidemiology), Universite’ Versailles Saint Quentin en Yvelines, 94807 Villejuif, France
| | - M. Cecconi
- Humanitas Clinical and Research Center, Via A. Manzoni 56, 20089 Rozzano – Milan, Italy
- Humanitas University, Department of Biomedical Sciences, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele – Milan, Italy
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Ripoll JG, Blackshear JL, Díaz-Gómez JL. Acute Cardiac Complications in Critical Brain Disease. Neurol Clin 2018; 35:761-783. [PMID: 28962813 DOI: 10.1016/j.ncl.2017.06.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Acute cardiac complications in critical brain disease should be understood as a clinical condition representing an intense brain-heart crosstalk and might mimic ischemic heart disease. Two main entities (neurogenic stunned myocardium [NSM] and stress cardiomyopathy) have been better characterized in the neurocritically ill patients and they portend worse clinical outcomes in these cases. The pathophysiology of NSM remains elusive. However, significant progress has been made on the early identification of neurocardiac compromise following acute critical brain disease. Effective prevention and treatment interventions are yet to be determined.
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Affiliation(s)
- Juan G Ripoll
- Department of Critical Care Medicine, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA
| | - Joseph L Blackshear
- Department of Cardiology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA
| | - José L Díaz-Gómez
- Departments of Critical Care Medicine, Anesthesiology and Neurologic Surgery, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
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44
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Ventura Spagnolo E, Mondello C, Di Mauro D, Vermiglio G, Asmundo A, Filippini E, Alibrandi A, Rizzo G. Analysis on sarcoglycans expression as markers of septic cardiomyopathy in sepsis-related death. Int J Legal Med 2018; 132:1685-1692. [PMID: 29644391 DOI: 10.1007/s00414-018-1840-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2017] [Accepted: 04/03/2018] [Indexed: 11/28/2022]
Abstract
The post-mortem assessment of sepsis-related death can be carry out by many methods recently suggested as microbiological and biochemical investigations. In these cases, the cause of death is a multiple organ dysfunction due to a dysregulated inflammatory response occurring after the failure of infection control process. It was highlighted also that the heart can be a target organ in sepsis which determines the so-called septic cardiomyopathy characterized by myocardial depression. Several mechanisms to explain the pathophysiology of septic cardiomyopathy were suggested, but very few studies about the structural alterations of cardiac cells responsible for myocardial depression were carried out. The aim of this study was to evaluate whether sarcoglycans (SG) were involved in septic cardiac damage analyzing their expression in sepsis-related deaths and, particularly, if these proteins can be used as markers of septic myocardial dysfunction. Cases of septic-related death confirmed by clinical and autopsy records were investigated and compared to a control group of traumatic deaths. Indirect immunofluorescence analysis was performed to analyze α-SG, β-SG, δ-SG, ζ-SG, ε-SG, and γ-SG. Decrease of fluorescence staining pattern for all tested sarcoglycans was observed in the septic-related deaths compared to normal fluorescence staining pattern of control group. These results provide new findings about the myocytes structural alterations due to sepsis and suggest that these proteins could be used in forensic assessment of septic cardiomyopathy.
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Affiliation(s)
- Elvira Ventura Spagnolo
- Legal Medicine Section, Department for Health Promotion and Mother-Child Care, University of Palermo, Via del Vespro, 129, 90127, Palermo, Italy.
| | - Cristina Mondello
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, via Consolare Valeria, 1, 98125, Messina, Italy
| | - Debora Di Mauro
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, via Consolare Valeria, 1, 98125, Messina, Italy
| | - Giovanna Vermiglio
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, via Consolare Valeria, 1, 98125, Messina, Italy
| | - Alessio Asmundo
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, via Consolare Valeria, 1, 98125, Messina, Italy
| | - Elena Filippini
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, via Consolare Valeria, 1, 98125, Messina, Italy
| | - Angela Alibrandi
- Department of Economics, Unit of Statistical and Mathematical Sciences, University of Messina, Via dei Verdi 75, 98122, Messina, Italy
| | - Giuseppina Rizzo
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, via Consolare Valeria, 1, 98125, Messina, Italy
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Rehberg S, Joannidis M, Whitehouse T, Morelli A. Landiolol for managing atrial fibrillation in intensive care. Eur Heart J Suppl 2018; 20:A15-A18. [PMID: 30188960 PMCID: PMC5909768 DOI: 10.1093/eurheartj/sux039] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Landiolol is an injectable ultrashort acting beta-blocker with high beta1 selectivity indicated for heart rate control of atrial fibrillation in the emergency and critical care setting. Accordingly, landiolol is associated with a significantly reduced risk of arterial hypotension and negative inotropic effects. Based on this particular profile along with the clinical experience in Japan for more than a decade landiolol represents a promising agent for the management of elevated heart rate and atrial fibrillation in intensive care patients even with catecholamine requirements. This article provides a review and perspective of landiolol for heart rate control in intensive care patients based on the current literature.
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Affiliation(s)
- Sebastian Rehberg
- Department of Anaesthesiology, University Hospital of Greifswald, Greifswald, Germany
| | - Michael Joannidis
- Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Innsbruck, Austria
| | - Tony Whitehouse
- Department of Critical Care and Anaesthesia, University Hospital Birmingham, Edgbaston, Birmingham, UK
| | - Andrea Morelli
- Department of Anesthesiology and Intensive Care Medicine, University of Rome "La Sapienza", Italy Policlinico Umberto I° Hospital, Viale del Policlinico 155, Rome, Italy
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46
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Galassi A, Turatello L, De Salvia A, Neri M, Turillazzi E, La Russa R, Viola RV, Frati P, Fineschi V. Septic cardiomyopathy: The value of lactoferrin and CD15 as specific markers to corroborate a definitive diagnosis. Int J Immunopathol Pharmacol 2018; 32:2058738418776526. [PMID: 29809052 PMCID: PMC5977426 DOI: 10.1177/2058738418776526] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Accepted: 04/19/2018] [Indexed: 01/18/2023] Open
Abstract
Current scientific consensus about the physiopathology in the progression from severe sepsis to septic shock and death focuses on myocardial contractile dysfunction. Nevertheless, objective parameters to establish a pathological correlate of a fatal outcome are lacking; then a cause of death due to sepsis can remain an unsolved problem. We first reviewed all death cases recorded at our institutions during the period from 2007 until 2015. Then, we conducted a retrospective study of a selected autopsy series of people who had received "sepsis" as cause of death. Two pathologists re-examined the heart sections while the most suitable myocardial sample for each case was stained for immunohistochemistry with antibodies targeted for specific inflammatory-related molecules. We used specific antibodies for the following markers: alpha-smooth muscle actin (alpha-SMA); fibronectin; matrix metallopeptidase 9 (MMP-9); intercellular adhesion molecule 1 (ICAM-1); caspase-3; lactoferrin (LF); cluster differentiation 15 (CD15). The statistical significance of differences was assessed using student's t-test for unpaired data or non-parametric Mann-Whitney or Wilcoxon tests for skewed variables or one-way analysis of variance and post hoc Scheffe's test for continuous variables and Pearson's χ2-test for discrete variables. Linear regression analysis was used to determine the presence of a correlation between continuous variables. At our institutions, 2220 deaths have been recorded during the period study. Sepsis accounted as a cause of death for the 20% of total. We finally enrolled 56 cases; of these, only 20 were positive for microbiological analysis. At histological examination, clear inflammation was detectable in the 32% of cases; otherwise, immunohistochemical reaction showed a positive reaction for LF and CD15 in more than a half cases (56%). We still ignore all the underlying mechanisms of sepsis and all its pathophysiological connections with cardiac metabolism; in this sense, we aim to corroborate the diagnostic value of anti-LF and anti-CD15 staining for the post-mortem detection of myocardial inflammation.
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Affiliation(s)
- Andrea Galassi
- Unit of Legal Medicine, S. Bortolo
General Hospital, Vicenza, Italy
| | | | | | - Margherita Neri
- Department of Morphology, Surgery and
Experimental Medicine, University of Ferrara, Ferrara, Italy
| | | | - Raffaele La Russa
- Department of Anatomical, Histological,
Forensic and Orthopedic Sciences, Sapienza University of Rome, Rome, Italy
| | - Rocco V Viola
- Department of Anatomical, Histological,
Forensic and Orthopedic Sciences, Sapienza University of Rome, Rome, Italy
| | - Paola Frati
- Department of Anatomical, Histological,
Forensic and Orthopedic Sciences, Sapienza University of Rome, Rome, Italy
| | - Vittorio Fineschi
- Department of Anatomical, Histological,
Forensic and Orthopedic Sciences, Sapienza University of Rome, Rome, Italy
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47
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Boerma E, Singer M. Beta-blockers in sepsis: time to reconsider current constraints? Br J Anaesth 2017; 119:560-561. [DOI: 10.1093/bja/aex266] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
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48
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Buschmann K, Chaban R, Emrich AL, Youssef M, Kornberger A, Beiras-Fernandez A, Vahl CF. Septic cardiomyopathy: evidence for a reduced force-generating capacity of human atrial myocardium in acute infective endocarditis. Innov Surg Sci 2017; 2:81-87. [PMID: 31579740 PMCID: PMC6753999 DOI: 10.1515/iss-2016-0202] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2016] [Accepted: 03/13/2017] [Indexed: 01/25/2023] Open
Abstract
Background This study analyzes the myocardial force-generating capacity in infective endocarditis (IE) using an experimental model of isolated human atrial myocardium. In vivo, it is difficult to decide whether or not alterations in myocardial contractile behavior are due to secondary effects associated with infection such as an altered heart rate, alterations of preload and afterload resulting from valvular defects, and altered humoral processes. Our in vitro model using isolated human myocardium, in contrast, guarantees exactly defined experimental conditions with respect to preload, afterload, and contraction frequency, thus not only preventing confounding by in vivo determinants of contractility but also excluding effects of other factors associated with sepsis, hemodynamics, humoral influences, temperature, and medical treatment. Methods We analyzed right atrial trabeculae (diameter 0.3–0.5 mm, initial length 5 mm) from 32 patients undergoing aortic and/or mitral valve replacement for acute valve incompetence caused by IE and 65 controls receiving aortic and/or mitral valve replacement for nonendocarditic valve incompetence. Isometric force amplitudes and passive resting force values measured at optimal length in the two groups were compared using Student’s t-test. Results There were no significant differences between the groups in terms of the passive resting force. The isometric force amplitude in the endocarditis group, however, was significantly lower than in the nonendocarditis group (p=0.001). In the endocarditis group, the calculated active force, defined as the isometric force amplitude minus the resting force, was significantly lower (p<0.0001) and the resting force/active force ratio was significantly higher (p<0.0001). Using linear regression to describe the function between resting force and active force, we identified a significant difference in slope (p<0.0001), with lower values found in the endocarditis group. Conclusion Our data suggest that the force-generating capacity of atrial myocardium is significantly reduced in patients with IE. In these patients, an elevated resting force is required to achieve a given force amplitude. It remains unclear, however, whether this is due to calcium desensitization of the contractile apparatus, presence of myocardial edema, fibrotic remodeling, disruption of contractile units, or other mechanisms.
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Affiliation(s)
- Katja Buschmann
- Department of Cardiothoracic and Vascular Surgery, Hospital of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany
| | - Ryan Chaban
- Department of Cardiothoracic and Vascular Surgery, Hospital of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Anna Lena Emrich
- Department of Cardiothoracic and Vascular Surgery, Hospital of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Marwan Youssef
- Department of Cardiothoracic and Vascular Surgery, Hospital of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Angela Kornberger
- Department of Cardiothoracic and Vascular Surgery, Hospital of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Andres Beiras-Fernandez
- Department of Cardiothoracic and Vascular Surgery, Hospital of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Christian Friedrich Vahl
- Department of Cardiothoracic and Vascular Surgery, Hospital of the Johannes Gutenberg-University Mainz, Mainz, Germany
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Kawazoe Y, Miyamoto K, Morimoto T, Yamamoto T, Fuke A, Hashimoto A, Koami H, Beppu S, Katayama Y, Itoh M, Ohta Y, Yamamura H. Effect of Dexmedetomidine on Mortality and Ventilator-Free Days in Patients Requiring Mechanical Ventilation With Sepsis: A Randomized Clinical Trial. JAMA 2017; 317:1321-1328. [PMID: 28322414 PMCID: PMC5469298 DOI: 10.1001/jama.2017.2088] [Citation(s) in RCA: 159] [Impact Index Per Article: 19.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
IMPORTANCE Dexmedetomidine provides sedation for patients undergoing ventilation; however, its effects on mortality and ventilator-free days have not been well studied among patients with sepsis. OBJECTIVES To examine whether a sedation strategy with dexmedetomidine can improve clinical outcomes in patients with sepsis undergoing ventilation. DESIGN, SETTING, AND PARTICIPANTS Open-label, multicenter randomized clinical trial conducted at 8 intensive care units in Japan from February 2013 until January 2016 among 201 consecutive adult patients with sepsis requiring mechanical ventilation for at least 24 hours. INTERVENTIONS Patients were randomized to receive either sedation with dexmedetomidine (n = 100) or sedation without dexmedetomidine (control group; n = 101). Other agents used in both groups were fentanyl, propofol, and midazolam. MAIN OUTCOMES AND MEASURES The co-primary outcomes were mortality and ventilator-free days (over a 28-day duration). Sequential Organ Failure Assessment score (days 1, 2, 4, 6, 8), sedation control, occurrence of delirium and coma, intensive care unit stay duration, renal function, inflammation, and nutrition state were assessed as secondary outcomes. RESULTS Of the 203 screened patients, 201 were randomized. The mean age was 69 years (SD, 14 years); 63% were male. Mortality at 28 days was not significantly different in the dexmedetomidine group vs the control group (19 patients [22.8%] vs 28 patients [30.8%]; hazard ratio, 0.69; 95% CI, 0.38-1.22; P = .20). Ventilator-free days over 28 days were not significantly different between groups (dexmedetomidine group: median, 20 [interquartile range, 5-24] days; control group: median, 18 [interquartile range, 0.5-23] days; P = .20). The dexmedetomidine group had a significantly higher rate of well-controlled sedation during mechanical ventilation (range, 17%-58% vs 20%-39%; P = .01); other outcomes were not significantly different between groups. Adverse events occurred in 8 (8%) and 3 (3%) patients in the dexmedetomidine and control groups, respectively. CONCLUSIONS AND RELEVANCE Among patients requiring mechanical ventilation, the use of dexmedetomidine compared with no dexmedetomidine did not result in statistically significant improvement in mortality or ventilator-free days. However, the study may have been underpowered for mortality, and additional research may be needed to evaluate this further. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01760967.
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Affiliation(s)
- Yu Kawazoe
- Division of Emergency and Critical Care Medicine, Tohoku University Graduate school of Medicine, Sendai, Japan
| | - Kyohei Miyamoto
- Department of Emergency and Critical Care Medicine, Wakayama Medical University, Wakayama, Japan
| | - Takeshi Morimoto
- Department of Clinical Epidemiology, Hyogo College of Medicine, Nishinomiya, Japan
| | - Tomonori Yamamoto
- Department of Trauma and Critical Care Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Akihiro Fuke
- Emergency and Urgent Medical Care Center, Osaka City General Hospital, Osaka, Japan
| | - Atsunori Hashimoto
- Emergency and Critical Care Center, Hyogo College of Medicine, Nishinomiya, Japan
| | - Hiroyuki Koami
- Advanced Emergency Care Center, Saga University Hospital, Saga, Japan
| | - Satoru Beppu
- Department of Emergency Medicine and Critical Care Medicine, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | - Yoichi Katayama
- Department of Emergency Medicine, Sapporo Medical University, Sapporo, Japan
| | - Makoto Itoh
- Department of Anesthesiology, Yamaguchi Grand Medical Center, Hofu, Japan
| | - Yoshinori Ohta
- Division of General Medicine, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | - Hitoshi Yamamura
- Department of Disaster and Critical Care Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
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Lanspa MJ, Shahul S, Hersh A, Wilson EL, Olsen TD, Hirshberg EL, Grissom CK, Brown SM. Associations among left ventricular systolic function, tachycardia, and cardiac preload in septic patients. Ann Intensive Care 2017; 7:17. [PMID: 28213737 PMCID: PMC5315651 DOI: 10.1186/s13613-017-0240-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Accepted: 02/01/2017] [Indexed: 01/25/2023] Open
Abstract
Background In sepsis, tachycardia may indicate low preload, adrenergic stimulation, or both. Adrenergic overstimulation is associated with septic cardiomyopathy. We sought to determine whether tachycardia was associated with left ventricular longitudinal strain, a measure of cardiac dysfunction. We hypothesized an association would primarily exist in patients with high preload. Methods We prospectively observed septic patients admitted to three study ICUs, who underwent early transthoracic echocardiography. We measured longitudinal strain using speckle tracking echocardiography and estimated preload status with an echocardiographic surrogate (E/e′). We assessed correlation between strain and heart rate in patients with low preload (E/e′ < 8), intermediate preload (E/e′ 8–14), and high preload (E/e′ > 14), adjusting for disease severity and vasopressor dependence. Results We studied 452 patients, of whom 298 had both measurable strain and preload. Abnormal strain (defined as >−17%) was present in 54%. Patients with abnormal strain had higher heart rates (100 vs. 93 beat/min, p = 0.001). After adjusting for vasopressor dependence, disease severity, and cardiac preload, we observed an association between heart rate and longitudinal strain (β = 0.05, p = 0.003). This association persisted among patients with high preload (β = 0.07, p = 0.016) and in patients with shock (β = 0.07, p = 0.01), but was absent in patients with low or intermediate preload and those not in shock. Conclusions Tachycardia is associated with abnormal left ventricular strain in septic patients with high preload. This association was not apparent in patients with low or intermediate preload. Electronic supplementary material The online version of this article (doi:10.1186/s13613-017-0240-2) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Michael J Lanspa
- Critical Care Echocardiography Service, Intermountain Medical Center, 5121 S Cottonwood St, Murray, UT, 84157, USA. .,Division of Pulmonary and Critical Care Medicine, University of Utah, 30 N 1900 E, 701 Wintrobe, Salt Lake City, UT, 84132, USA.
| | - Sajid Shahul
- Department of Anesthesia, Critical Care, and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.,Department of Anesthesia and Critical Care, University of Chicago, 5841 South Maryland Avenue, Chicago, IL, 60637, USA
| | - Andrew Hersh
- Division of Pulmonary and Critical Care Medicine, University of Utah, 30 N 1900 E, 701 Wintrobe, Salt Lake City, UT, 84132, USA
| | - Emily L Wilson
- Critical Care Echocardiography Service, Intermountain Medical Center, 5121 S Cottonwood St, Murray, UT, 84157, USA
| | - Troy D Olsen
- Critical Care Echocardiography Service, Intermountain Medical Center, 5121 S Cottonwood St, Murray, UT, 84157, USA
| | - Eliotte L Hirshberg
- Critical Care Echocardiography Service, Intermountain Medical Center, 5121 S Cottonwood St, Murray, UT, 84157, USA.,Division of Pulmonary and Critical Care Medicine, University of Utah, 30 N 1900 E, 701 Wintrobe, Salt Lake City, UT, 84132, USA.,Division of Pediatric Critical Care, Department of Pediatrics, University of Utah, 295 Chipeta Way, Salt Lake City, UT, 84108, USA
| | - Colin K Grissom
- Critical Care Echocardiography Service, Intermountain Medical Center, 5121 S Cottonwood St, Murray, UT, 84157, USA.,Division of Pulmonary and Critical Care Medicine, University of Utah, 30 N 1900 E, 701 Wintrobe, Salt Lake City, UT, 84132, USA
| | - Samuel M Brown
- Critical Care Echocardiography Service, Intermountain Medical Center, 5121 S Cottonwood St, Murray, UT, 84157, USA.,Division of Pulmonary and Critical Care Medicine, University of Utah, 30 N 1900 E, 701 Wintrobe, Salt Lake City, UT, 84132, USA
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