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Grundmann D, Neubarth-Mayer J, Müller C, Becker F, Reichart D, Stark K, Grabmaier U, Deseive S, Rizas KD, Hausleiter J, Hagl C, Mehilli J, Massberg S, Orban M. Progress of Angiographic Cardiac Allograft Vasculopathy in Patients With Long-Term Transplantation: Longitudinal Evaluation of Its Association With Dyslipidemia Patterns. Am J Cardiol 2025; 238:47-54. [PMID: 39613280 DOI: 10.1016/j.amjcard.2024.11.031] [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: 09/08/2024] [Revised: 11/09/2024] [Accepted: 11/23/2024] [Indexed: 12/01/2024]
Abstract
Cardiac allograft vasculopathy (CAV) is a progressive disease with limited options for secondary prevention. Ways to manage lipid parameters and dyslipidemia patterns in care after transplantation remain unclear. In this longitudinal study, we included 32 patients with long-term heart transplantations (median interval after transplant 13.8 years) with angiographic manifest CAV. In 299 matched nonstented segments at 3 distinct time points ([TPs] 0 to 2, with median intervals of 2 years, respectively), progress of diameter stenosis (Δ%DS) defined CAV progress. Values above the median of maximal Δ%DS defined substantial CAV progress. Category of left ventricular ejection fraction was evaluated at TP0 and TP3 (2 years after TP2). Findings were correlated with dyslipidemia patterns at TP0, and lipid variations at follow-up (TP1 to TP3). Analyses included routine lipid assessment, and triglycerides/high-density lipoprotein-cholesterol ratio (TG/HDL-c) and atherogenic index of plasma (AIP). At TP1 and TP2, patients with increase of TG/HDL-c ≥0.1 (p = 0.02, respectively) and with increase of AIP (p = 0.01 and p = 0.049, respectively) presented a greater maximal Δ%DS. Dyslipidemia patterns at TP0 did not show a relevant association with CAV progress. At TP2, increase of TGs, TG/HDL-c, and AIP were associated with substantial CAV progress (odds ratio [OR] 5.0, p = 0.046, and OR 9.2, p = 0.01, OR 6.6, p = 0.02, respectively). At TP3, patients with CAV-related worsening of left ventricular ejection fraction category presented with a greater increase of TG/HDL-c (p = 0.03). Although findings at TP0 did not affect CAV progress, an increase of TG/HDL-c could define patients at greater risk of CAV progress and CAV-related deterioration of graft function.
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Affiliation(s)
- David Grundmann
- Departments of Medicine I, University Hospital, LMU Munich, Germany
| | | | - Christoph Müller
- Departments of Cardiac Surgery, LMU University Hospital, LMU Munich, Germany
| | - Finn Becker
- Departments of Medicine I, University Hospital, LMU Munich, Germany
| | - Daniel Reichart
- Departments of Medicine I, University Hospital, LMU Munich, Germany
| | - Konstantin Stark
- Departments of Medicine I, University Hospital, LMU Munich, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Berlin, Germany
| | - Ulrich Grabmaier
- Medizinische Klinik I, Landshut-Achdorf Hospital, Landshut, Germany; Departments of Medicine I, University Hospital, LMU Munich, Germany
| | - Simon Deseive
- Departments of Medicine I, University Hospital, LMU Munich, Germany
| | - Konstantinos D Rizas
- Departments of Medicine I, University Hospital, LMU Munich, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Berlin, Germany
| | - Jörg Hausleiter
- Departments of Medicine I, University Hospital, LMU Munich, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Berlin, Germany
| | - Christian Hagl
- Departments of Cardiac Surgery, LMU University Hospital, LMU Munich, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Berlin, Germany
| | - Julinda Mehilli
- Medizinische Klinik I, Landshut-Achdorf Hospital, Landshut, Germany; Departments of Medicine I, University Hospital, LMU Munich, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Berlin, Germany
| | - Steffen Massberg
- Departments of Medicine I, University Hospital, LMU Munich, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Berlin, Germany
| | - Madeleine Orban
- Departments of Medicine I, University Hospital, LMU Munich, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Berlin, Germany.
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2
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Sakowitz S, Bakhtiyar SS, Mallick S, Pereira S, Nelson JS, Parikh R, Higgins RSD, Shemin RJ, Benharash P. Insurance-Based Disparities in Cardiac Allograft Vasculopathy After Heart Transplantation Are Mediated by Care at High-Volume Centers. Ann Thorac Surg 2025:S0003-4975(25)00072-4. [PMID: 39864773 DOI: 10.1016/j.athoracsur.2025.01.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 12/10/2024] [Accepted: 01/16/2025] [Indexed: 01/28/2025]
Abstract
BACKGROUND Socioeconomic disadvantage and Medicaid insurance have been linked with inferior survival after heart transplantation, yet the contributing mechanisms remain to be elucidated. We evaluated the association of Medicaid with the development of cardiac allograft vasculopathy (CAV). METHODS We considered heart transplant recipients aged ≥18 years within the 2004-2022 Organ Procurement and Transplantation Network. CAV was defined as any evidence of angiographic coronary disease. Institutional volume was computed, with hospitals in the highest quartile (≥19 cases/y) categorized as high-volume centers. Patients were stratified by insurance into the Medicaid and Non-Medicaid cohorts. The study period was divided into the pre-Affordable Care Act (ACA; 2004-2013) and post-ACA eras (2014-2022). RESULTS Of 37,073 heart transplant recipients, 4875 (13%) were insured by Medicaid. The overall incidence of CAV was 31%. After risk-adjustment, Medicaid insurance was linked with significantly greater likelihood of developing CAV over 5 years (Hazard Ratio [HR], 1.08, 95% CI, 1.01-1.16). Importantly, this effect seems to have emerged in the post-ACA era (Pre-ACA HR, 1.07, 95% CI 0.84-1.36; Post-ACA HR, 1.11, 95% CI, 1.02-1.21). Furthermore, among patients at high-volume centers, Medicaid insurance was linked with similar CAV likelihood (HR, 1.04, 95% CI, 0.95-1.14). Yet, considering those treated at non-high-volume centers, Medicaid was associated with significantly greater CAV hazard (HR, 1.14, 95% CI, 1.03-1.26). Overall, Medicaid remained associated with inferior patient (HR, 1.31, 95% CI, 1.21-1.42) and allograft survival at 5 years (HR, 1.29, 95% CI, 1.19-1.39). CONCLUSIONS Medicaid-insured recipients faced inferior survival and greater risk of CAV over 5 years. Our work encourages closer follow-up and treatment for vulnerable populations in the months and years post-transplantation.
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Affiliation(s)
- Sara Sakowitz
- Cardiovascular Outcomes Research Laboratories (CORELAB), University of California, Los Angeles, California
| | - Syed Shahyan Bakhtiyar
- Cardiovascular Outcomes Research Laboratories (CORELAB), University of California, Los Angeles, California; Department of Surgery, University of Colorado, Aurora, Colorado
| | - Saad Mallick
- Cardiovascular Outcomes Research Laboratories (CORELAB), University of California, Los Angeles, California
| | - Sara Pereira
- Division of Cardiothoracic Surgery, Department of Surgery, University of Utah, Salt Lake City, Utah
| | - Jennifer S Nelson
- Division of Cardiac Surgery, Nemours Children's Hospital, Orlando, Florida
| | - Rushi Parikh
- Division of Cardiology, Department of Medicine, University of California, Los Angeles, California
| | | | - Richard J Shemin
- Division of Cardiac Surgery, Department of Surgery, University of California, Los Angeles, California
| | - Peyman Benharash
- Cardiovascular Outcomes Research Laboratories (CORELAB), University of California, Los Angeles, California; Division of Cardiac Surgery, Department of Surgery, University of California, Los Angeles, California.
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O'Hara PE, Gorrai A, Farr M, Peltz M, Beaini H, Moayedi Y, Chih S, Truby LK. Revisiting Biomarkers of Cardiac Allograft Vasculopathy: Addressing the Achilles Heel of Heart Transplantation. Curr Heart Fail Rep 2024; 21:580-590. [PMID: 39414739 DOI: 10.1007/s11897-024-00685-7] [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] [Accepted: 09/04/2024] [Indexed: 10/18/2024]
Abstract
Nearly half of heart transplant recipients will be diagnosed with cardiac allograft vasculopathy (CAV) within five years after transplantation. Advanced CAV can lead to worsening heart failure as well as arrhythmias and sudden cardiac death. The only curative therapy for end-stage CAV is re-transplantation. Current diagnostic methods are invasive and limited by poor sensitivity in early disease. Despite its high prevalence in the post-transplantpopulation, the underlying pathophysiology of this condition has yet to be fully described. It is thought to be primarily related to endothelial dysfunction, immune activation, and cardiometabolic disease. Biomarkers reflecting these underlying processes, particularly endothelial injury and immune activation, have shown early promise in discriminating prevalent CAV. Next-generation sequencing technologies such as proteomic and transcriptomic profiling have also provided further insight into the pathophysiology of CAV through the identification of novel biomarkers. Ultimately, these biomarkers may have a role in not only diagnosing CAV but also highlighting potential targets for disease-specific therapies. In this article, we review the current data for biomarkers in CAV and discuss future directions for biomarker identification..
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Affiliation(s)
- Patrick E O'Hara
- University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Ananya Gorrai
- University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Maryjane Farr
- University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Matthias Peltz
- University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Hadi Beaini
- University of Texas Southwestern Medical Center, Dallas, TX, USA
| | | | - Sharon Chih
- University of Ottawa Heart Institute, Ottawa, ON, Canada
| | - Lauren K Truby
- University of Texas Southwestern Medical Center, Dallas, TX, USA.
- Advanced Heart Failure and Transplantation, Department of Medicine, Division of Cardiology, UT Southwestern Medical Center, 5959 Harry Hines Boulevard, Dallas, TX, 75390, USA.
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4
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Ulrich S, Arnold L, Michel S, Tengler A, Rosenthal L, Hausleiter J, Mueller CS, Schnabel B, Stark K, Rizas K, Grabmaier U, Mehilli J, Jakob A, Fischer M, Birnbaum J, Hagl C, Massberg S, Haas N, Pozza RD, Orban M. Influence of donor age and donor-recipient age difference on intimal hyperplasia in pediatric patients with young and adult donors vs. adult patients after heart transplantation. Clin Res Cardiol 2024:10.1007/s00392-024-02477-4. [PMID: 38913171 DOI: 10.1007/s00392-024-02477-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Accepted: 06/11/2024] [Indexed: 06/25/2024]
Abstract
AIM Optimal selection and allocation of donor hearts is a relevant aspect in transplantation medicine. Donor age and cardiac allograft vasculopathy (CAV) affect post-transplant mortality. To what extent donor age impacts intimal hyperplasia (CAVIH) in pediatric and adult patients after heart transplantation (HTx) is understudied. METHODS In a cohort of 98 HTx patients, 58 pediatric (24.1% with adult donors) and 40 adult patients, we assessed the effect of donor age and donor-recipient age difference (D-R) on the continuous parameter of maximal intima thickness (mIT) in optical coherence tomography. We evaluated their predictive value regarding higher mIT and the prevalence of CAVIH, defined as mIT > 0.3 mm, and compared it to established CAV risk factors. RESULTS In the overall population, donor age correlated with mIT (p < 0.001), while in the pediatric subpopulation, both donor age and D-R correlated with mIT (p < 0.001 and p = 0.002, respectively). In the overall population, donor age was a main predictor of higher mIT and CAVIH (p = 0.001 and p = 0.01, respectively) in addition to post-transplant interval, arterial hypertension, and dyslipidemia. In the pediatric patients, dyslipidemia remained a main predictor of both higher mIT and CAVIH (p = 0.004 and p = 0.040, respectively), while donor age and D-R were not. CONCLUSION While there was an effect of the non-modifiable parameter of donor age regarding maximal intimal thickness, a stronger association was seen between the modifiable risk factor dyslipidemia and higher maximal intimal thickness and CAVIH in both the overall population and the pediatric subpopulation.
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Affiliation(s)
- Sarah Ulrich
- Division of Pediatric Cardiology and Intensive Care Medicine, University Hospital, LMU Munich, Munich, Germany
| | - Leonie Arnold
- Division of Pediatric Cardiology and Intensive Care Medicine, University Hospital, LMU Munich, Munich, Germany
| | - Sebastian Michel
- Department of Heart Surgery, Ludwig-Maximilians-University, Klinikum Großhadern, Munich, Germany
| | - Anja Tengler
- Division of Pediatric Cardiology and Intensive Care Medicine, University Hospital, LMU Munich, Munich, Germany
| | - Laura Rosenthal
- Department of Heart Surgery, Ludwig-Maximilians-University, Klinikum Großhadern, Munich, Germany
| | - Jörg Hausleiter
- Department of Medicine I, University Hospital, LMU Munich, Marchioninistraße 15, 81377, Munich, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
| | - Christoph S Mueller
- Department of Heart Surgery, Ludwig-Maximilians-University, Klinikum Großhadern, Munich, Germany
| | - Brigitte Schnabel
- Department of Heart Surgery, Ludwig-Maximilians-University, Klinikum Großhadern, Munich, Germany
| | - Konstantin Stark
- Department of Medicine I, University Hospital, LMU Munich, Marchioninistraße 15, 81377, Munich, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
| | - Konstantinos Rizas
- Department of Medicine I, University Hospital, LMU Munich, Marchioninistraße 15, 81377, Munich, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
| | - Ulrich Grabmaier
- Department of Medicine I, University Hospital, LMU Munich, Marchioninistraße 15, 81377, Munich, Germany
| | - Julinda Mehilli
- Department of Medicine I, University Hospital, LMU Munich, Marchioninistraße 15, 81377, Munich, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
- Medizinische Klinik I, Landshut-Achdorf Hospital, Landshut, Germany
| | - Andre Jakob
- Division of Pediatric Cardiology and Intensive Care Medicine, University Hospital, LMU Munich, Munich, Germany
| | - Marcus Fischer
- Division of Pediatric Cardiology and Intensive Care Medicine, University Hospital, LMU Munich, Munich, Germany
| | - Julia Birnbaum
- Division of Pediatric Cardiology and Intensive Care Medicine, University Hospital, LMU Munich, Munich, Germany
| | - Christian Hagl
- Department of Heart Surgery, Ludwig-Maximilians-University, Klinikum Großhadern, Munich, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
| | - Steffen Massberg
- Department of Medicine I, University Hospital, LMU Munich, Marchioninistraße 15, 81377, Munich, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
| | - Nikolaus Haas
- Division of Pediatric Cardiology and Intensive Care Medicine, University Hospital, LMU Munich, Munich, Germany
| | - Robert Dalla Pozza
- Division of Pediatric Cardiology and Intensive Care Medicine, University Hospital, LMU Munich, Munich, Germany
| | - Madeleine Orban
- Department of Medicine I, University Hospital, LMU Munich, Marchioninistraße 15, 81377, Munich, Germany.
- German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany.
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Sponga S, Vendramin I, Ferrara V, Marinoni M, Valdi G, Di Nora C, Nalli C, Benedetti G, Piani D, Lechiancole A, Parpinel M, Bortolotti U, Livi U. Metabolic Syndrome and Heart Transplantation: An Underestimated Risk Factor? Transpl Int 2024; 37:11075. [PMID: 38525207 PMCID: PMC10959251 DOI: 10.3389/ti.2024.11075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Accepted: 01/02/2024] [Indexed: 03/26/2024]
Abstract
Metabolic Syndrome (MetS), a multifactorial condition that increases the risk of cardio-vascular events, is frequent in Heart-transplant (HTx) candidates and worsens with immunosuppressive therapy. The aim of the study was to analyze the impact of MetS on long-term outcome of HTx patients. Since 2007, 349 HTx patients were enrolled. MetS was diagnosed if patients met revised NCEP-ATP III criteria before HTx, at 1, 5 and 10 years of follow-up. MetS was present in 35% of patients pre-HTx and 47% at 1 year follow-up. Five-year survival in patients with both pre-HTx (65% vs. 78%, p < 0.01) and 1 year follow-up MetS (78% vs 89%, p < 0.01) was worst. At the univariate analysis, risk factors for mortality were pre-HTx MetS (HR 1.86, p < 0.01), hypertension (HR 2.46, p < 0.01), hypertriglyceridemia (HR 1.50, p=0.03), chronic renal failure (HR 2.95, p < 0.01), MetS and diabetes at 1 year follow-up (HR 2.00, p < 0.01; HR 2.02, p < 0.01, respectively). MetS at 1 year follow-up determined a higher risk to develop Coronary allograft vasculopathy at 5 and 10 year follow-up (25% vs 14% and 44% vs 25%, p < 0.01). MetS is an important risk factor for both mortality and morbidity post-HTx, suggesting the need for a strict monitoring of metabolic disorders with a careful nutritional follow-up in HTx patients.
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Affiliation(s)
- Sandro Sponga
- Department of Medicine (DAME), University of Udine, Udine, Italy
- Cardiothoracic Department, University Hospital of Udine, Udine, Italy
| | - Igor Vendramin
- Cardiothoracic Department, University Hospital of Udine, Udine, Italy
| | - Veronica Ferrara
- Department of Medicine (DAME), University of Udine, Udine, Italy
| | - Michela Marinoni
- Department of Medicine (DAME), University of Udine, Udine, Italy
| | - Giulia Valdi
- Department of Medicine (DAME), University of Udine, Udine, Italy
| | - Concetta Di Nora
- Cardiothoracic Department, University Hospital of Udine, Udine, Italy
| | - Chiara Nalli
- Cardiothoracic Department, University Hospital of Udine, Udine, Italy
| | | | - Daniela Piani
- Cardiothoracic Department, University Hospital of Udine, Udine, Italy
| | | | - Maria Parpinel
- Department of Medicine (DAME), University of Udine, Udine, Italy
| | - Uberto Bortolotti
- Cardiothoracic Department, University Hospital of Udine, Udine, Italy
| | - Ugolino Livi
- Department of Medicine (DAME), University of Udine, Udine, Italy
- Cardiothoracic Department, University Hospital of Udine, Udine, Italy
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6
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Rodenas-Alesina E, Aleksova N, Stubbs M, Foroutan F, Kozuszko S, Posada JD, McDonald M, Moayedi Y, Ross H, Dipchand A. Cardiac allograft vasculopathy and survival in pediatric heart transplant recipients transitioned to adult care. J Heart Lung Transplant 2024; 43:229-237. [PMID: 37704160 DOI: 10.1016/j.healun.2023.09.005] [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: 03/06/2023] [Revised: 08/31/2023] [Accepted: 09/05/2023] [Indexed: 09/15/2023] Open
Abstract
BACKGROUND Cardiac allograft vasculopathy (CAV) is an important cause of mortality after pediatric heart transplantation (HT) but there is a paucity of data regarding its incidence and impact on survival in pediatric recipients transitioned to adult care. METHODS We conducted a retrospective review of consecutive pediatric HT patients from 1989 to 2017 at the Hospital for Sick Children who transitioned to adult care at ≥18 years at Toronto General Hospital. We evaluated the incidence of International Society of Heart and Lung Transplantation CAV grade ≥1 using competing risk models. We assessed the association between all-cause mortality and CAV using Cox proportional hazards and used Kaplan Meier methods to evaluate all-cause mortality stratified by CAV and transplant era (1989-2001, 2002-2017). RESULTS Ninety-six patients were transitioned to adult care by January 2022, of which 53 underwent repeat coronary angiography as adults. CAV was newly diagnosed in 49% patients after transition to adult care. The overall incidence of CAV was 3.9 cases per 100 person-years. There was no difference in the adjusted incidence of CAV according to transplant era (subdistribution hazard ratios = 1.17, 95% confidence interval (CI) 0.54-2.66). CAV was associated with a higher risk of death in the early era (hazard ratio (HR) 10.29, 95% CI 2.16-49.96), but not in the recent era (HR 1.61, 95% 0.35-7.47). CONCLUSIONS There is a role for continued CAV surveillance after the transition to adult care. The implications of diagnosing CAV after the transition to adult care require further study, particularly because the risk of death in pediatric HT recipients diagnosed with CAV in the more recent era may be attenuated compared to the earlier HT era.
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Affiliation(s)
| | - Natasha Aleksova
- Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada; Women's College Hospital, Toronto, Ontario, Canada.
| | - Michael Stubbs
- Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada
| | - Farid Foroutan
- Ted Rogers Centre for Heart Research, University Health Network, Toronto, Ontario, Canada
| | - Stella Kozuszko
- Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada
| | - Juan Duero Posada
- Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada
| | - Michael McDonald
- Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada
| | - Yasbanoo Moayedi
- Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada
| | - Heather Ross
- Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada
| | - Anne Dipchand
- Hospital for Sick Children, Toronto, Ontario, Canada
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7
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Ma B, Gavzy SJ, France M, Song Y, Lwin HW, Kensiski A, Saxena V, Piao W, Lakhan R, Iyyathurai J, Li L, Paluskievicz C, Wu L, WillsonShirkey M, Mongodin EF, Mas VR, Bromberg JS. Rapid intestinal and systemic metabolic reprogramming in an immunosuppressed environment. BMC Microbiol 2023; 23:394. [PMID: 38066426 PMCID: PMC10709923 DOI: 10.1186/s12866-023-03141-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Accepted: 11/30/2023] [Indexed: 12/18/2023] Open
Abstract
Intrinsic metabolism shapes the immune environment associated with immune suppression and tolerance in settings such as organ transplantation and cancer. However, little is known about the metabolic activities in an immunosuppressive environment. In this study, we employed metagenomic, metabolomic, and immunological approaches to profile the early effects of the immunosuppressant drug tacrolimus, antibiotics, or both in gut lumen and circulation using a murine model. Tacrolimus induced rapid and profound alterations in metabolic activities within two days of treatment, prior to alterations in gut microbiota composition and structure. The metabolic profile and gut microbiome after seven days of treatment was distinct from that after two days of treatment, indicating continuous drug effects on both gut microbial ecosystem and host metabolism. The most affected taxonomic groups are Clostriales and Verrucomicrobiae (i.e., Akkermansia muciniphila), and the most affected metabolic pathways included a group of interconnected amino acids, bile acid conjugation, glucose homeostasis, and energy production. Highly correlated metabolic changes were observed between lumen and serum metabolism, supporting their significant interactions. Despite a small sample size, this study explored the largely uncharacterized microbial and metabolic events in an immunosuppressed environment and demonstrated that early changes in metabolic activities can have significant implications that may serve as antecedent biomarkers of immune activation or quiescence. To understand the intricate relationships among gut microbiome, metabolic activities, and immune cells in an immune suppressed environment is a prerequisite for developing strategies to monitor and optimize alloimmune responses that determine transplant outcomes.
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Affiliation(s)
- Bing Ma
- Institute of Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
- Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
| | - Samuel J Gavzy
- Department of Surgery, University of Maryland Medical Center, Baltimore, MD, 21201, USA
- Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
| | - Michael France
- Institute of Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
- Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
| | - Yang Song
- Institute of Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
| | - Hnin Wai Lwin
- Institute of Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
| | - Allison Kensiski
- Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
| | - Vikas Saxena
- Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
| | - Wenji Piao
- Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
| | - Ram Lakhan
- Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
| | - Jegan Iyyathurai
- Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
| | - Lushen Li
- Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
| | - Christina Paluskievicz
- Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
| | - Long Wu
- Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
| | - Marina WillsonShirkey
- Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
| | - Emmanuel F Mongodin
- Institute of Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
- Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
- Division of Lung Diseases, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA
| | - Valeria R Mas
- Department of Surgery, University of Maryland Medical Center, Baltimore, MD, 21201, USA
| | - Jonathan S Bromberg
- Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
- Department of Surgery, University of Maryland Medical Center, Baltimore, MD, 21201, USA.
- Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
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8
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Chang A, Martin KA, Colvin M, Bellumkonda L. Role of ascorbic acid in cardiac allograft vasculopathy. Clin Transplant 2023; 37:e15153. [PMID: 37792313 DOI: 10.1111/ctr.15153] [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: 06/08/2023] [Revised: 09/04/2023] [Accepted: 09/22/2023] [Indexed: 10/05/2023]
Abstract
PURPOSE OF THE REVIEW Cardiac allograft vasculopathy (CAV) is a progressive fibroproliferative disease which occurs after heart transplantation and is associated with significant long-term morbidity and mortality. Currently available strategies including statins, mammalian target of rapamycin (mTOR) inhibitors, and revascularization, have limited overall effectiveness in treating this pathology once the disease process is established. mTOR inhibitors, while effective when used early in the disease process, are not well tolerated, and hence not routinely used in post-transplant care. RECENT DATA Recent work on rodent models have given us a novel mechanistic understanding of effects of ascorbic acid in preventing CAV. TET methyl cytosine dioxygenase2 (TET2) reduces vascular smooth muscle cell (VSMC) apoptosis and intimal thickening. TET2 is repressed by interferon γ (IFNγ) in the setting of CAV. Ascorbic acid has been shown to promote TET2 activity and attenuate allograft vasculopathy in animal models and CAV progression in a small clinical trial. SUMMARY CAV remains a challenging disease process and needs better preventative strategies. Ascorbic acid improves endothelial dysfunction, reduces reactive oxygen species, and prevents development of intimal hyperplasia by preventing smooth muscle cell apoptosis and hyperproliferation. Further large-scale randomized control studies of ascorbic acid are needed to establish the role in routine post-transplant management.
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Affiliation(s)
- Alyssa Chang
- Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Kathleen A Martin
- Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Monica Colvin
- Division of Cardiology, Department of Medicine, Yale University, New Haven, Connecticut, USA
| | - Lavanya Bellumkonda
- Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA
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9
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Ma B, Gavzy SJ, France M, Song Y, Lwin HW, Kensiski A, Saxena V, Piao W, Lakhan R, Iyyathurai J, Li L, Paluskievicz C, Wu L, WillsonShirkey M, Mongodin EF, Mas VR, Bromberg J. Rapid intestinal and systemic metabolic reprogramming in an immunosuppressed environment. RESEARCH SQUARE 2023:rs.3.rs-3364037. [PMID: 37790403 PMCID: PMC10543476 DOI: 10.21203/rs.3.rs-3364037/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/05/2023]
Abstract
Intrinsic metabolism shapes the immune environment associated with immune suppression and tolerance in settings such as organ transplantation and cancer. However, little is known about the metabolic activities in an immunosuppressive environment. In this study, we employed metagenomic, metabolomic, and immunological approaches to profile the early effects of the immunosuppressant drug tacrolimus, antibiotics, or both in gut lumen and circulation using a murine model. Tacrolimus induced rapid and profound alterations in metabolic activities within two days of treatment, prior to alterations in gut microbiota composition and structure. The metabolic profile and gut microbiome after seven days of treatment was distinct from that after two days of treatment, indicating continuous drug effects on both gut microbial ecosystem and host metabolism. The most affected taxonomic groups are Clostriales and Verrucomicrobiae (i.e., Akkermansia muciniphila), and the most affected metabolic pathways included a group of interconnected amino acids, bile acid conjugation, glucose homeostasis, and energy production. Highly correlated metabolic changes were observed between lumen and serum metabolism, supporting their significant interactions. Despite a small sample size, this study explored the largely uncharacterized microbial and metabolic events in an immunosuppressed environment and demonstrated that early changes in metabolic activities can have significant implications that may serve as antecedent biomarkers of immune activation or quiescence. To understand the intricate relationships among gut microbiome, metabolic activities, and immune cells in an immune suppressed environment is a prerequisite for developing strategies to monitor and optimize alloimmune responses that determine transplant outcomes.
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Affiliation(s)
- Bing Ma
- University of Maryland, Baltimore
| | | | | | | | | | | | | | | | | | | | | | | | - Long Wu
- University of Maryland, Baltimore
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10
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Ozcan I, Toya T, Cohen-Shelly M, Park HW, Ahmad A, Ozcan A, Noseworthy PA, Kapa S, Lerman LO, Attia ZI, Kushwaha SS, Friedman PA, Lerman A. Artificial intelligence-derived cardiac ageing is associated with cardiac events post-heart transplantation. EUROPEAN HEART JOURNAL. DIGITAL HEALTH 2022; 3:516-524. [PMID: 36710906 PMCID: PMC9779895 DOI: 10.1093/ehjdh/ztac051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 09/08/2022] [Indexed: 02/01/2023]
Abstract
Aims An artificial intelligence algorithm detecting age from 12-lead electrocardiogram (ECG) has been suggested to reflect 'physiological age'. An increased physiological age has been associated with a higher risk of cardiac mortality in the non-transplant population. We aimed to investigate the utility of this algorithm in patients who underwent heart transplantation (HTx). Methods and results A total of 540 patients were studied. The average ECG ages within 1 year before and after HTx were used to represent pre- and post-HTx ECG ages. Major adverse cardiovascular event (MACE) was defined as any coronary revascularization, heart failure hospitalization, re-transplantation, and mortality. Recipient pre-transplant ECG age (mean 63 ± 11 years) correlated significantly with recipient chronological age (mean 49 ± 14 years, R = 0.63, P < 0.0001), while post-transplant ECG age (mean 54 ± 10 years) correlated with both the donor (mean 32 ± 13 years, R = 0.45, P < 0.0001) and the recipient ages (R = 0.38, P < 0.0001). During a median follow-up of 8.8 years, 307 patients experienced MACE. Patients with an increase in ECG age post-transplant showed an increased risk of MACE [hazard ratio (HR): 1.58, 95% confidence interval (CI): (1.24, 2.01), P = 0.0002], even after adjusting for potential confounders [HR: 1.58, 95% CI: (1.19, 2.10), P = 0.002]. Conclusion Electrocardiogram age-derived cardiac ageing after transplantation is associated with a higher risk of MACE. This study suggests that physiological age change of the heart might be an important determinant of MACE risk post-HTx.
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Affiliation(s)
- Ilke Ozcan
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA
| | - Takumi Toya
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA,Division of Cardiology, National Defense Medical College, Tokorozawa, Namiki, 3 Chome−2 Saitama, Japan
| | - Michal Cohen-Shelly
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA
| | - Hyun Woong Park
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA,Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Gyeongsangnam-do, 52727, South Korea
| | - Ali Ahmad
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA,Department of Internal Medicine, Saint Louis University School of Medicine, 1402 S Grand Blvd, St. Louis, MO 63104, USA
| | - Alp Ozcan
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA
| | - Peter A Noseworthy
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA
| | - Suraj Kapa
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA
| | - Lilach O Lerman
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA,Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA
| | - Zachi I Attia
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA
| | - Sudhir S Kushwaha
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA
| | - Paul A Friedman
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA
| | - Amir Lerman
- Corresponding author. Tel: +1 507 255 4152, Fax: +1 507 255 7798,
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11
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Orban M, Kuehl A, Dischl D, Müller C, Ulrich S, Petzold T, Rizas KD, Orban M, Braun D, Hausleiter J, Hagl C, Mehilli J, Massberg S. Fibrotic plaques in heart transplanted patients and their association with insulin resistance syndrome and Lp(a). Int J Cardiol 2022; 363:218-224. [PMID: 35772579 DOI: 10.1016/j.ijcard.2022.06.062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Revised: 06/23/2022] [Accepted: 06/24/2022] [Indexed: 11/05/2022]
Abstract
BACKGROUND Angiographic evidence of cardiac allograft vasculopathy (CAVangio) is a major limiting factor to survival after heart transplantation (HTx). Prevention of CAVangio is therefore most relevant. Whether modifiable risk factors could be targeted for the prevention of fibrotic plaques, that are common and related to CAVangio, is not clear. METHODS AND RESULTS In a cohort of 74 consecutive HTx patients (median post-transplant interval 9.2 [4.1-15.5] years), we used the high resolution of optical coherence tomography (OCT) to quantify angulation parameters (maximal and mean arc) and plaque load (mean arc*relative plaque length) of fibrotic plaques. Mean arc was defined as the mean value of all angulation measurements per patient. We assessed the association between cardiovascular risk factors and OCT findings. Linear regression analysis showed a significant association of TG/HDL-c with mean fibrotic arc (12.7 [3.9-21.5], p = 0.006) and fibrotic plaque load (2298 [617-3979], p = 0.009) after adjustment for recipient age and sex. We used the median value of fibrotic plaque load to define high fibrotic plaque load. In binary logistic regression analysis, TG/HDL-c (odds ratio [OR] 1.81 with 95% CI [1.09-3.03], p = 0.02) and Lp(a) (OR 1.02 [1.00-1.05], p = 0.02) were associated with high fibrotic plaque load. Multivariable logistic regression analysis confirmed Lp(a) as significant predictor of high fibrotic plaque load (OR 1.03 [1.01-1.05], p = 0.02). CONCLUSION TG/HDL-c ratio, a surrogate of insulin resistance syndrome, and Lp(a) were significantly associated with fibrotic plaque in HTx patients. Insulin resistance syndrome and Lp(a) might therefore represent additional targets for CAV prevention.
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Affiliation(s)
- Madeleine Orban
- Department of Medicine I, University Hospital, LMU Munich, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Berlin, Germany.
| | - Anne Kuehl
- Department of Medicine I, University Hospital, LMU Munich, Germany
| | - Dominic Dischl
- Department of Medicine I, University Hospital, LMU Munich, Germany
| | - Christoph Müller
- Department of Heart Surgery, University Hospital, LMU Munich, Germany
| | - Sarah Ulrich
- Department of Paediatric Cardiology and Intensive Care Medicine, University Hospital, LMU Munich, Germany
| | - Tobias Petzold
- Department of Medicine I, University Hospital, LMU Munich, Germany
| | - Konstantinos D Rizas
- Department of Medicine I, University Hospital, LMU Munich, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Berlin, Germany
| | - Martin Orban
- Department of Medicine I, University Hospital, LMU Munich, Germany
| | - Daniel Braun
- Department of Medicine I, University Hospital, LMU Munich, Germany
| | - Jörg Hausleiter
- Department of Medicine I, University Hospital, LMU Munich, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Berlin, Germany
| | - Christian Hagl
- Department of Heart Surgery, University Hospital, LMU Munich, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Berlin, Germany
| | - Julinda Mehilli
- Department of Medicine I, University Hospital, LMU Munich, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Berlin, Germany
| | - Steffen Massberg
- Department of Medicine I, University Hospital, LMU Munich, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Berlin, Germany
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12
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Bogle C, Marma Perak A, Wilkens SJ, Aljiffry A, Rychlik K, Costello JM, Lloyd-Jones DM, Pahl E. Cardiovascular health in pediatric heart transplant patients. BMC Cardiovasc Disord 2022; 22:139. [PMID: 35365073 PMCID: PMC8973961 DOI: 10.1186/s12872-022-02575-z] [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: 02/17/2021] [Accepted: 03/21/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Ideal "cardiovascular health" (CVH)-optimal diet, exercise, nonsmoking, BMI, BP, lipids, and glucose-is associated with healthy longevity in adults. Pediatric heart transplant (HT) patients may be at risk for suboptimal CVH. METHODS Single-center retrospective study of HT patients 2003-2014 who survived 1 year post-transplant. Five CVH metrics were collected at listing, 1, 3 and 5 years post-transplant (diet and exercise were unavailable). CVH was scored by summing individual metrics: ideal = 2, intermediate = 1, and poor = 0 points; total scores of 8-10 points were considered high (favorable). CVH was compared between HT patients and the US pediatric population (GP) utilizing NHANES 2007-2016. Logistic regression was performed to examine the association of CVH 1 year post-transplant with a composite adverse outcome (death, re-listing, coronary vasculopathy, or chronic kidney disease) 3 years post-transplant. RESULTS We included 110 HT patients (median age at HT: 6 years [range 0.1-21]) and 19,081 NHANES participants. CVH scores among HT patients were generally high at listing (75%), 1 (74%), 3 (87%) and 5 (76%) years post-transplant and similar to GP, but some metrics (e.g., glucose) were worse among HT patients. Among HT patients, CVH was poorer with older age and non-Caucasian race/ethnicity. Per 1-point higher CVH score, the demographic-adjusted OR for adverse outcomes was 0.95 (95% CI, 0.7-1.4). CONCLUSIONS HT patients had generally favorable CVH, but some metrics were unfavorable and CVH varied by age and race/ethnicity. No significant association was detected between CVH and adverse outcomes in this small sample, but study in a larger sample is warranted.
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Affiliation(s)
- Carmel Bogle
- Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA. .,University of Maryland Children's Heart Program, Baltimore, MD, USA.
| | - Amanda Marma Perak
- Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.,Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Sarah J Wilkens
- University of Louisville School of Medicine, Louisville, KY, USA
| | | | - Karen Rychlik
- Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.,Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - John M Costello
- Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.,Medical University of South Carolina Children's Health, Charleston, SC, USA
| | | | - Elfriede Pahl
- Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.,Northwestern University Feinberg School of Medicine, Chicago, IL, USA
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13
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Pober JS, Chih S, Kobashigawa J, Madsen JC, Tellides G. Cardiac allograft vasculopathy: current review and future research directions. Cardiovasc Res 2021; 117:2624-2638. [PMID: 34343276 PMCID: PMC8783389 DOI: 10.1093/cvr/cvab259] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 07/02/2021] [Accepted: 07/29/2021] [Indexed: 12/25/2022] Open
Abstract
Cardiac allograft vasculopathy (CAV) is a pathologic immune-mediated remodelling of the vasculature in transplanted hearts and, by impairing perfusion, is the major cause of late graft loss. Although best understood following cardiac transplantation, similar forms of allograft vasculopathy occur in other vascularized organ grafts and some features of CAV may be shared with other immune-mediated vasculopathies. Here, we describe the incidence and diagnosis, the nature of the vascular remodelling, immune and non-immune contributions to pathogenesis, current therapies, and future areas of research in CAV.
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MESH Headings
- Adaptive Immunity
- Animals
- Coronary Artery Disease/epidemiology
- Coronary Artery Disease/immunology
- Coronary Artery Disease/metabolism
- Coronary Artery Disease/pathology
- Coronary Vessels/immunology
- Coronary Vessels/metabolism
- Coronary Vessels/pathology
- Endothelial Cells/immunology
- Endothelial Cells/metabolism
- Endothelial Cells/pathology
- Graft Rejection/epidemiology
- Graft Rejection/immunology
- Graft Rejection/metabolism
- Graft Rejection/pathology
- Graft Survival
- Heart Transplantation/adverse effects
- Humans
- Immunity, Innate
- Muscle, Smooth, Vascular/immunology
- Muscle, Smooth, Vascular/metabolism
- Muscle, Smooth, Vascular/pathology
- Myocytes, Smooth Muscle/immunology
- Myocytes, Smooth Muscle/metabolism
- Myocytes, Smooth Muscle/pathology
- Risk Factors
- Signal Transduction
- Treatment Outcome
- Vascular Remodeling
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Affiliation(s)
- Jordan S Pober
- Department of Immunobiology, Pathology and Dermatology, Yale School of Medicine, 10 Amistad Street, New Haven CT 06520-8089, USA
| | - Sharon Chih
- Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON, Canada
| | - Jon Kobashigawa
- Department of Medicine, Cedars-Sinai Smidt Heart Institute, Los Angeles, CA, USA
| | - Joren C Madsen
- Division of Cardiac Surgery and Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA, USA
| | - George Tellides
- Department of Surgery (Cardiac Surgery), Yale School of Medicine, New Haven, CT, USA
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14
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Ozcan I, Toya T, Corban MT, Ahmad A, Lerman LO, Kushwaha SS, Lerman A. Peripheral microvascular dysfunction is associated with plaque progression and adverse long-term outcomes in heart transplant patients. ESC Heart Fail 2021; 8:5266-5274. [PMID: 34510802 PMCID: PMC8712915 DOI: 10.1002/ehf2.13610] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 08/17/2021] [Accepted: 09/01/2021] [Indexed: 11/21/2022] Open
Abstract
Aims Cardiac allograft vasculopathy (CAV) is the major cause of increased morbidity and mortality after heart transplantation. Peripheral endothelial dysfunction (PED) is associated with early atherosclerosis and future risk of major adverse cardiovascular events (MACE) in non‐heart transplant population. We aimed to investigate the association of PED with future MACE, and plaque progression assessed by intravascular ultrasound (IVUS) after heart transplantation. Methods and results We included 66 transplant patients who underwent serial IVUS surveillance for CAV and baseline assessment of peripheral endothelial function using reactive hyperaemia peripheral arterial tonometry. PED was defined as reactive hyperaemia index < 2. The primary endpoint of the study was to investigate the association of PED with CAV progression assessed by intravascular ultrasound (IVUS). CAV progression was assessed as the change (Δ) in plaque volume divided by segment length, and Δ plaque index (plaque volume/vessel volume), adjusted for the time between IVUS measurements (median 3.0 [2.2, 3.1] years). The secondary endpoint was to investigate the association between PED and future MACE, which was defined as any incident of revascularization, heart failure hospitalization, stroke, myocardial infarction, re‐transplantation, and death. Patients with PED (n = 27) had more yearly plaque progression (0.50 ± 0.66 vs. 0.15 ± 0.50 mm3/mm/year, P = 0.02) and a higher Δ plaque index (2.41 ± 2.53% vs. 0.69 ± 2.22%, P = 0.01). Patients with PED were more likely to experience MACE during a median follow‐up of 8.2 years (interquartile range [7.6, 8.4]), after adjustment for potential cofounders such as age, high‐density lipoprotein cholesterol levels, total rejection score, baseline International Society for Heart & Lung Transplantation CAV grade, and indication of transplantation. (hazard ratio 2.15, 95% confidence interval [1.09, 4.23], P = 0.03). Conclusions Peripheral endothelial dysfunction is associated with increased plaque progression and adverse long‐term cardiovascular outcomes in transplant patients. PED assessment might be a useful clinical tool for risk stratification after heart transplantation.
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Affiliation(s)
- Ilke Ozcan
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55902, USA
| | - Takumi Toya
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55902, USA.,Division of Cardiology, National Defense Medical College, Tokorozawa, Japan
| | - Michel T Corban
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55902, USA
| | - Ali Ahmad
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55902, USA
| | - Lilach O Lerman
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA
| | - Sudhir S Kushwaha
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55902, USA
| | - Amir Lerman
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55902, USA
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15
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Ozcan I, Toya T, Corban MT, Ahmad A, Loeffler D, Morse D, Lerman LO, Kushwaha SS, Lerman A. Circulating Progenitor Cells Are Associated With Plaque Progression And Long-Term Outcomes In Heart Transplant Patients. Cardiovasc Res 2021; 118:1703-1712. [PMID: 34132771 DOI: 10.1093/cvr/cvab203] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 05/10/2021] [Accepted: 06/14/2021] [Indexed: 11/13/2022] Open
Abstract
AIMS Circulating progenitor cells (CPCs) play a role in vascular repair and plaque stability, while osteocalcin (OC) expressing CPCs have been linked to unstable plaque and adverse cardiovascular outcomes. However, their role in cardiac allograft vasculopathy (CAV) has not been elucidated. This cohort study aimed to investigate the contribution of CPCs on CAV progression and cardiovascular events after heart transplantation. METHODS AND RESULTS A total of 80 heart transplant patients (mean age 55 ± 14 years, 72% male) undergoing annual intravascular ultrasound (IVUS) had fresh CPCs marked by CD34, CD133, and OC counted in peripheral blood using flow cytometry, on the same day as baseline IVUS. CAV progression was assessed by IVUS as the change (Δ) in plaque volume divided by segment length (PV/SL), adjusted for the time between IVUS measurements (median 3.0, interquartile range (IQR) [2.8, 3.1] years), and was defined as ΔPV/SL that is above the median ΔPV/SL of study population. Major adverse cardiac events (MACE) was defined as any incident of revascularization, myocardial infarction, heart failure admission, re-transplantation, stroke and death. Patients with higher CD34+CD133+ CPCs had a decreased risk of CAV progression (odds ratio 0.58, 95% confidence interval [CI] [0.37, 0.92], p = 0.01) and MACE (hazard ratio [HR] 0.79, 95% CI [0.66, 0.99], p = 0.05) during a median (IQR) follow up of 8.0 years (7.2, 8.3). Contrarily, higher OC+ cell counts were associated with an increased risk of MACE (HR 1.26, 95% CI [1.03, 1.57], p = 0.02). CONCLUSIONS Lower levels of CD34+CD133+ CPCs are associated with plaque progression and adverse long-term outcomes in patients who underwent allograft heart transplantation. In contrast, higher circulating OC+ levels are associated with adverse long term outcomes. Thus, CPCs might play a role in amelioration of transplant vasculopathy, while OC expression by these cells might play a role in progression. TRANSLATIONAL PERSPECTIVE The results of the current study suggest lower levels of circulating CD34+CD133+ cell levels are associated with cardiac allograft vasculopathy progression and future adverse cardiovascular events, while higher OC+ cell levels are associated with a greater risk of future cardiovascular events. Further studies confirming our findings might elucidate the role of circulating progenitor cells in the pathophysiology of CAV. Moreover, our findings might support the use of circulating progenitors as biomarkers, as well as the notion of cell therapy as potential treatment option for CAV, a disease with severe burden and limited treatment options.
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Affiliation(s)
- Ilke Ozcan
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA
| | - Takumi Toya
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA.,Division of Cardiology, National Defense Medical College, Tokorozawa, Saitama, Japan
| | - Michel T Corban
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA
| | - Ali Ahmad
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA
| | - Darrell Loeffler
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA
| | - David Morse
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA
| | - Lilach O Lerman
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA
| | - Sudhir S Kushwaha
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA
| | - Amir Lerman
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA
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16
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Long-Term Prognostic Value of Coronary CTA in Orthotopic Heart Transplant Recipients. AJR Am J Roentgenol 2021; 216:1216-1221. [PMID: 33624522 DOI: 10.2214/ajr.20.23535] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
OBJECTIVE. This study aimed to evaluate the long-term prognostic value of coronary CTA (CCTA) in heart transplant recipients. MATERIALS AND METHODS. The records of 114 patients who had undergone a heart transplant (mean age, 61.7 ± 11.1 [SD] years; 83.3% men) and who underwent CCTA for the surveillance of coronary allograft vasculopathy (CAV) from June 2007 to December 2017 were retrospectively evaluated for the occurrence of major adverse cardiovascular events (MACEs) (cardiac death, nonfatal myocardial infarction, unstable angina requiring hospitalization, coronary revascularization, cardiac arrhythmias, stroke, and retransplant). Patients were classified according to the presence of nonobstructive CAV (lumen reduction < 50%) or obstructive disease (lumen reduction ≥ 50%) and using a coronary segment involvement score (SIS). Differences in MACE rate between groups were compared. RESULTS. Obstructive CAV was observed in 12 heart transplant recipients (10.5%). During a mean follow-up of 67.5 ± 41.4 months the overall rates of MACE were 50% and 14.7% in patients with obstructive and nonobstructive CAV, respectively (p < .05), resulting in an odds ratio for MACE of 6 (95% CI, 1.7-21.2). Comparison of event-free survival showed a hazard ratio (HR) of 5 (95% CI, 1.95-13; p =. 004) for patients with obstructive disease. The presence of four or more stenotic coronary segments (SIS ≥ 4) was associated with a higher rate of events (HR, 3.46; 95% CI, 1.46-8.23). CONCLUSION. In patients who have undergone a heart transplant, CCTA offers a significant long-term prognostic impact on the prediction of MACEs.
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17
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Mallah SI, Atallah B, Moustafa F, Naguib M, El Hajj S, Bader F, Mehra MR. Evidence-based pharmacotherapy for prevention and management of cardiac allograft vasculopathy. Prog Cardiovasc Dis 2020; 63:194-209. [DOI: 10.1016/j.pcad.2020.03.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Accepted: 03/17/2020] [Indexed: 01/08/2023]
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Genuth SM, Vlachos H, Brooks MM, Bantle JP, Chaitman BR, Green J, Kelsey SF, King SB, McBane R, Sako EY, Schneider DJ, Steffes M, Frye RL. BARI 2D: A Reanalysis Focusing on Cardiovascular Events. Mayo Clin Proc 2019; 94:2249-2262. [PMID: 31590967 PMCID: PMC6832788 DOI: 10.1016/j.mayocp.2019.04.015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2018] [Revised: 04/09/2019] [Accepted: 04/10/2019] [Indexed: 01/04/2023]
Abstract
OBJECTIVE To reanalyze the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial using a new composite cardiovascular disease (CVD) outcome to determine how best to treat patients with type 2 diabetes mellitus and stable coronary artery disease. PATIENTS AND METHODS From January 1, 2001, to November 30, 2008, 2368 patients with type 2 diabetes mellitus and angiographically proven coronary artery disease were randomly assigned to insulin-sensitizing (IS) or insulin-providing (IP) therapy and simultaneously to coronary revascularization (REV) or no or delayed REV (intensive medical therapy [MED]), with all patients receiving intensive medical treatment. The outcome of this analysis was a composite of 8 CVD events. RESULTS Four-year Kaplan-Meier rates for the composite CVD outcome were 35.8% (95% CI, 33.1%-38.5%) with IS therapy and 41.6% (95% CI, 38.7%-44.5%) with IP therapy (P=.004). Much of this difference was associated with lower in-trial levels of fibrinogen, C-reactive protein, and hemoglobin A1c with IS therapy. Four-year composite CVD rates were 32.7% (95% CI, 30.0%-35.4%) with REV and 44.7% (95% CI, 41.8%-47.6%) with MED (P<.001). A beneficial effect of IS vs IP therapy was present with REV (27.7%; 95% CI, 24.0%-31.4% vs 37.5%; 95% CI, 33.6%-41.4%; P<.001), but not with MED (43.6%; 95% CI, 39.5%-47.7% vs 45.7%; 95% CI, 41.6%-49.8%; P=.37) (homogeneity, P=.05). This interaction between IS therapy and REV was limited to participants preselected for coronary artery bypass grafting (CABG). The lowest composite CVD rates occurred in patients preselected for CABG and assigned to IS therapy and REV (17.3%; 95% CI, 11.8%-22.8%). CONCLUSION In the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial, the IS treatment strategy and the REV treatment strategy each reduces cardiovascular events. The combination of IS drugs and CABG results in the lowest risk of subsequent CVD events. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00006305.
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Affiliation(s)
- Saul M Genuth
- Division of Clinical and Molecular Endocrinology, Department of Medicine, Case Western Reserve University, Cleveland, OH
| | - Helen Vlachos
- Epidemiology Data Center, University of Pittsburgh, PA
| | | | - John P Bantle
- Department of Medicine, University of Minnesota, Minneapolis; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis
| | - Bernard R Chaitman
- Division of Cardiology, Department of Medicine, St. Louis University, MO
| | - Jennifer Green
- Division of Endocrinology, Department of Medicine, Duke University Medical Center, Durham, NC
| | | | | | | | - Edward Y Sako
- Department of Cardiothoracic Surgery, University of Texas Health Science Center at San Antonio
| | - David J Schneider
- Department of Medicine, University of Vermont Medical Center, Burlington
| | - Michael Steffes
- Department of Medicine, University of Minnesota, Minneapolis; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis
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Kim JH, Ha JI, Park JM, Lee JS, Ahn AL, Oh EJ, Choi JK, Kweon HJ, Cho DY. Association of High-Risk Drinking with Metabolic Syndrome and Its Components in Elderly Korean Men: The Korean National Health and Nutrition Examination Survey 2010-2012. Korean J Fam Med 2018; 39:233-238. [PMID: 29976000 PMCID: PMC6056403 DOI: 10.4082/kjfm.17.0024] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2017] [Accepted: 06/15/2017] [Indexed: 01/10/2023] Open
Abstract
Background Previous studies have examined the association between alcohol consumption and metabolic syndrome (MetS) in adults, but studies in the elderly are lacking. We examined the relationship between high-risk alcohol consumption and MetS in elderly Korean men using the Alcohol Use Disorders Identification Test (AUDIT) questionnaire from the 2010–2012 Korean National Health and Nutrition Examination Survey. Methods Among 25,534 subjects, 2,807 were men >60 years of age; after exclusions, we included 2,088 men in the final analysis. We categorized the study participants into three groups according to AUDIT score: low risk (0–7), intermediate risk (8–14), and high risk (≥15 points). Results Among the study population, 17.0% of the men were high-risk drinkers, who had the highest mean waist circumference, systolic and diastolic blood pressure (BP), fasting plasma glucose (FPG), and triglyceride (TG) levels. The overall prevalence of MetS was 41.9% in the elderly men, and it was significantly higher in the group with high (48.3%) versus low (31.9%) AUDIT scores. The prevalence of MetS components (elevated BP, high FPG, high TG, and low high-density lipoprotein cholesterol) was associated with a high AUDIT score. The odds ratios (95%confidence interval) of the high-risk group for MetS, elevated BP, and high TG were 1.40 (1.03–1.89), 1.82 (1.28– 2.60), and 1.77 (1.30–2.41) after adjustment for confounding variables. Conclusion AUDIT score was correlated with most MetS components in elderly Korean men.
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Affiliation(s)
- Ji-Hyun Kim
- Department of Family Medicine, Konkuk University Medical Center, Seoul, Korea
| | - Jeong-Im Ha
- Department of Family Medicine, Konkuk University Medical Center, Seoul, Korea
| | - Jae-Min Park
- Department of Family Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Ji Sun Lee
- Department of Family Medicine, Konkuk University Medical Center, Seoul, Korea
| | - Ah-Leum Ahn
- Department of Family Medicine, Konkuk University Medical Center, Seoul, Korea
| | - Eun-Jung Oh
- Department of Family Medicine, Konkuk University Medical Center, Seoul, Korea
| | - Jae-Kyung Choi
- Department of Family Medicine, Konkuk University Medical Center, Seoul, Korea
| | - Hyuk-Jung Kweon
- Department of Family Medicine, Konkuk University Medical Center, Seoul, Korea
| | - Dong-Yung Cho
- Department of Family Medicine, Konkuk University Medical Center, Seoul, Korea
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20
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Peled Y, Lavee J, Raichlin E, Katz M, Arad M, Kassif Y, Peled A, Asher E, Elian D, Har-Zahav Y, Shlomo N, Freimark D, Goldenberg I, Klempfner R. Early aspirin initiation following heart transplantation is associated with reduced risk of allograft vasculopathy during long-term follow-up. Clin Transplant 2017; 31. [DOI: 10.1111/ctr.13133] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/03/2017] [Indexed: 11/26/2022]
Affiliation(s)
- Yael Peled
- The Leviev Heart Center; Sheba Medical Center; Tel Hashomer Israel
- Sackler School of Medicine; Tel Aviv University; Tel Aviv Israel
| | - Jacob Lavee
- The Leviev Heart Center; Sheba Medical Center; Tel Hashomer Israel
- Sackler School of Medicine; Tel Aviv University; Tel Aviv Israel
| | - Eugenia Raichlin
- Cardiology Department; Loyola University Medical Center; Maywood IL USA
| | - Moshe Katz
- The Leviev Heart Center; Sheba Medical Center; Tel Hashomer Israel
- Sackler School of Medicine; Tel Aviv University; Tel Aviv Israel
| | - Michael Arad
- The Leviev Heart Center; Sheba Medical Center; Tel Hashomer Israel
- Sackler School of Medicine; Tel Aviv University; Tel Aviv Israel
| | - Yigal Kassif
- The Leviev Heart Center; Sheba Medical Center; Tel Hashomer Israel
- Sackler School of Medicine; Tel Aviv University; Tel Aviv Israel
| | - Amir Peled
- Clalit Health Services; Central Region; Tel Aviv Israel
| | - Elad Asher
- The Leviev Heart Center; Sheba Medical Center; Tel Hashomer Israel
- Sackler School of Medicine; Tel Aviv University; Tel Aviv Israel
| | - Dan Elian
- The Leviev Heart Center; Sheba Medical Center; Tel Hashomer Israel
- Sackler School of Medicine; Tel Aviv University; Tel Aviv Israel
| | - Yedael Har-Zahav
- The Leviev Heart Center; Sheba Medical Center; Tel Hashomer Israel
| | - Nir Shlomo
- Israeli Association for Cardiovascular Trials; Sheba Medical Center; Israel
| | - Dov Freimark
- The Leviev Heart Center; Sheba Medical Center; Tel Hashomer Israel
- Sackler School of Medicine; Tel Aviv University; Tel Aviv Israel
| | - Ilan Goldenberg
- The Leviev Heart Center; Sheba Medical Center; Tel Hashomer Israel
- Sackler School of Medicine; Tel Aviv University; Tel Aviv Israel
- Israeli Association for Cardiovascular Trials; Sheba Medical Center; Israel
| | - Robert Klempfner
- The Leviev Heart Center; Sheba Medical Center; Tel Hashomer Israel
- Sackler School of Medicine; Tel Aviv University; Tel Aviv Israel
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21
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Alperi A, Pascual I, Molina BD, Silva I, Lorca R, Hernández-Vaquero D, Avanzas P, Lambert JL, de la Tassa CM. Fever, Malaise, and Dyspnea in a Diabetic Heart Transplant Patient: A Case Report. Transplant Proc 2017; 49:1667-1671. [PMID: 28838461 DOI: 10.1016/j.transproceed.2017.04.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2016] [Revised: 04/10/2017] [Accepted: 04/27/2017] [Indexed: 10/19/2022]
Abstract
Patients with solid-organ transplants usually present at the emergency department with nonspecific symptoms. The physician should consider a great variety of syndromes and diseases, given the greater risk that solid-organ transplant patients carry because of immunosuppression and transplant-related conditions. Myocardial infarction caused by cardiac allograft vasculopathy must be always suspected and ruled out, even when initial symptoms do not orientate in that direction. We present a case that conjugates signs that can be present in different pathologies. It shows that fever is not always related to infection or rejection but could also appear in acute cardiac allograft vasculopathy. It emphasizes the need of a multi-disciplinary team led by a heart transplant specialist when dealing with this sort of clinical case.
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Affiliation(s)
- A Alperi
- Department of Cardiology, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain.
| | - I Pascual
- Department of Cardiology, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain
| | - B D Molina
- Department of Cardiology, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain
| | - I Silva
- Department of Cardiology, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain
| | - R Lorca
- Department of Cardiology, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain
| | - D Hernández-Vaquero
- Department of Cardiology, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain
| | - P Avanzas
- Department of Cardiology, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain
| | - J L Lambert
- Department of Cardiology, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain
| | - C M de la Tassa
- Department of Cardiology, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain
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López-Sainz Á, Barge-Caballero E, Barge-Caballero G, Couto-Mallón D, Paniagua-Martin MJ, Seoane-Quiroga L, Iglesias-Gil C, Herrera-Noreña JM, Cuenca-Castillo JJ, Vázquez-Rodríguez JM, Crespo-Leiro MG. Late graft failure in heart transplant recipients: incidence, risk factors and clinical outcomes. Eur J Heart Fail 2017; 20:385-394. [DOI: 10.1002/ejhf.886] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Revised: 03/27/2017] [Accepted: 04/12/2017] [Indexed: 11/10/2022] Open
Affiliation(s)
| | | | | | | | | | | | - Carmen Iglesias-Gil
- Servicio de Cirugía Cardiaca; Complexo Hospitalario Universitario de A Coruña (CHUAC), Servicio Galego de Saúde (SERGAS), Instituto de Investigación Biomédica de A Coruña (INIBIC), Universidad de A Coruña (UDC), Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV); La Coruna Spain
| | - José M. Herrera-Noreña
- Servicio de Cirugía Cardiaca; Complexo Hospitalario Universitario de A Coruña (CHUAC), Servicio Galego de Saúde (SERGAS), Instituto de Investigación Biomédica de A Coruña (INIBIC), Universidad de A Coruña (UDC), Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV); La Coruna Spain
| | - José J. Cuenca-Castillo
- Servicio de Cirugía Cardiaca; Complexo Hospitalario Universitario de A Coruña (CHUAC), Servicio Galego de Saúde (SERGAS), Instituto de Investigación Biomédica de A Coruña (INIBIC), Universidad de A Coruña (UDC), Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV); La Coruna Spain
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Abstract
Although the number of available donor hearts severely limits the epidemiologic impact of heart transplantation on patients with heart failure, patients with end-stage heart failure unresponsive to medical management currently have no other viable alternatives. Destination therapy with a ventricular assist device is the closest toward approaching clinical reality but has been plagued with problems of infection and stroke. The purpose of this review is to summarize recent developments in the field that may broaden the clinical impact of heart transplantation. For example, novel methods of cardiac preservation are being designed to safely evaluate and utilize “extended criteria” donors. Surgical techniques and medical management have reduced the incidence of postoperative right heart failure, and immunosuppressive regimens promise to limit chronic graft vascular disease.
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24
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Hollis IB, Reed BN, Moranville MP. Medication management of cardiac allograft vasculopathy after heart transplantation. Pharmacotherapy 2015; 35:489-501. [PMID: 26011142 DOI: 10.1002/phar.1580] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Cardiac allograft vasculopathy (CAV) is a common complication following heart transplantation (HT), resulting in diminished graft survival. The preferred strategy for preventing CAV is optimal medical management; however, for patients who develop CAV, delaying disease progression through effective medication management is equally important. A review of the literature regarding medication management of CAV was conducted via a search of the MEDLINE database. Studies were included if they were published in English, conducted in humans ≥ 18 years of age or older, and used noninvestigational medications. Immunosuppressive medications such as the antiproliferative mycophenolate, the calcineurin inhibitor tacrolimus, and the proliferation signal inhibitors sirolimus and everolimus have been shown to prevent the development of CAV. Certain cardiovascular medications, such as HMG-CoA reductase inhibitors (statins), gemfibrozil, calcium channel blockers, and angiotensin-converting enzyme inhibitors, have also demonstrated efficacy in preventing this disease process. Prevention of CAV has also been observed with prophylaxis against cytomegalovirus infection and antioxidant medications. Despite being commonly used in HT patients, neither antiplatelet agents nor glycemic control have proved effective at preventing CAV. Only sirolimus has been shown to arrest the progress of existing CAV.
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Affiliation(s)
- Ian B Hollis
- Department of Pharmacy, University of North Carolina Hospitals, Chapel Hill, North Carolina
| | - Brent N Reed
- School of Pharmacy, University of Maryland, Baltimore, Maryland
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25
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Singh N, Heggermont W, Fieuws S, Vanhaecke J, Van Cleemput J, De Geest B. Endothelium-enriched microRNAs as diagnostic biomarkers for cardiac allograft vasculopathy. J Heart Lung Transplant 2015. [DOI: 10.1016/j.healun.2015.06.008] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
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Skorić B, Čikeš M, Ljubas Maček J, Baričević Ž, Škorak I, Gašparović H, Biočina B, Miličić D. Cardiac allograft vasculopathy: diagnosis, therapy, and prognosis. Croat Med J 2015; 55:562-76. [PMID: 25559827 PMCID: PMC4295072 DOI: 10.3325/cmj.2014.55.562] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Development of cardiac allograft vasculopathy represents the major determinant of long-term survival in patients after heart transplantation. Due to graft denervation, these patients seldom present with classic symptoms of angina pectoris, and the first clinical presentations are progressive heart failure or sudden cardiac death. Although coronary angiography remains the routine technique for coronary artery disease detection, it is not sensitive enough for screening purposes. This is especially the case in the first year after transplantation when diffuse and concentric vascular changes can be easily detected only by intravascular ultrasound. The treatment of the established vasculopathy is disappointing, so the primary effort should be directed toward early prevention and diagnosis. Due to diffuse vascular changes, revascularization procedures are restricted only to a relatively small proportion of patients with favorable coronary anatomy. Percutaneous coronary intervention is preferred over surgical revascularization since it leads to better acute results and patient survival. Although there is no proven long-term advantage of drug-eluting stents for the treatment of in-stent restenosis, they are preferred over bare-metal stents. Severe vasculopathy has a poor prognosis and the only definitive treatment is retransplantation. This article reviews the present knowledge on the pathogenesis, diagnosis, treatment, and prognosis of cardiac allograft vasculopathy.
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Affiliation(s)
- Boško Skorić
- Bosko Skoric, University of Zagreb School of Medicine, Department of Cardiovascular Diseases, University Hospital Center Zagreb, Kispaticeva 12, 10 000 Zagreb, Croatia,
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27
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Eholié SP, Lacombe K, Krain A, Diallo Z, Ouiminga M, Campa P, Bouchaud O, Bissagnene E, Girard PM. Metabolic disorders and cardiovascular risk in treatment-naive HIV-infected patients of sub-saharan origin starting antiretrovirals: impact of westernized lifestyle. AIDS Res Hum Retroviruses 2015; 31:384-92. [PMID: 25707418 DOI: 10.1089/aid.2014.0164] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
In a cohort of HIV-infected patients of sub-Saharan origin we describe the incidence of metabolic syndrome, insulin resistance, and lipodystrophy after 3 years of combined antiretroviral therapy, and model the 10-year risk of cardiovascular diseases, while taking into account environmental factors. This is a multinational, prospective cohort study conducted in HIV outpatient clinics from four tertiary care centers set in France and Côte d'Ivoire. The participants were HIV-infected, treatment-naive patients eligible to start antiretroviral treatment and were of sub-Saharan African origin. The main outcome measures were the incidence of metabolic syndrome, insulin resistance, and lipodystrophy, and the assessment of the 10-year risk of cardiovascular diseases using Framingham risk prediction, D.A.D. Cardiovascular Disease Risk, and WHO/ISH prediction charts. Of 245 patients followed for up to 3 years, the incidence of metabolic syndrome, insulin resistance, and lipodystrophy was 5.5, 8.5, and 6.8 per 100 person-years of follow-up (cumulative incidence: 14.4%, 19.2%, and 18.1%, respectively). Living in France as well as female gender and being overweight were risk factors for metabolic disorders as whole and only first generation protease inhibitors were marginally associated with metabolic syndrome. Cardiovascular risk as modeled through the three equations was high in all patients with the synergistic and deleterious effect of living in France compared to Côte d'Ivoire. This cohort study shows how the synergy between HIV, antiretroviral (ARV) exposure, and westernization of life style in a cohort of HIV-infected patients of sub-Saharan origin leads to a progressive increase in the risk of lipodystrophy, as well as metabolic syndrome and insulin resistance, all associated with increased cardiovascular risk.
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Affiliation(s)
- Serge Paul Eholié
- Department of Infectious Diseases and Tropical Medicine, Treichville University Hospital, Abidjan, Côte d'Ivoire
| | - Karine Lacombe
- University of Pierre and Marie Curie, Paris VI, France
- Department of Infectious Diseases and Tropical Medicine, Hospital Saint-Antoine, AP-HP, Paris, France
- Sorbonne Universités, UPMC University Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France
| | - Alysa Krain
- Department of Infectious Diseases and Tropical Medicine, Hospital Saint-Antoine, AP-HP, Paris, France
| | - Zelica Diallo
- Department of Infectious Diseases and Tropical Medicine, Treichville University Hospital, Abidjan, Côte d'Ivoire
| | - Mariama Ouiminga
- Department of Infectious Diseases and Tropical Medicine, Treichville University Hospital, Abidjan, Côte d'Ivoire
| | - Pauline Campa
- Department of Infectious Diseases and Tropical Medicine, Hospital Saint-Antoine, AP-HP, Paris, France
| | - Olivier Bouchaud
- Department of Infectious Diseases and Tropical Medicine, Hospital Avicenne, AP-HP, Bobigny, France
| | - Emmanuel Bissagnene
- Department of Infectious Diseases and Tropical Medicine, Treichville University Hospital, Abidjan, Côte d'Ivoire
| | - Pierre-Marie Girard
- University of Pierre and Marie Curie, Paris VI, France
- Department of Infectious Diseases and Tropical Medicine, Hospital Saint-Antoine, AP-HP, Paris, France
- Sorbonne Universités, UPMC University Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France
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Time-to-Referral, Use, and Efficacy of Cardiac Rehabilitation After Heart Transplantation. Transplantation 2015; 99:594-601. [DOI: 10.1097/tp.0000000000000361] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
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Luo CM, Chou NK, Chi NH, Chen YS, Yu HY, Chang CH, Wang CH, Tsao CI, Wang SS. The effect of statins on cardiac allograft survival. Transplant Proc 2015; 46:920-4. [PMID: 24767381 DOI: 10.1016/j.transproceed.2013.11.016] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2013] [Accepted: 11/06/2013] [Indexed: 11/24/2022]
Abstract
PURPOSE In addition to having a lipid-lowering effect, statins also have an anti-inflammatory effect that may reduce allograft dysfunction by preventing cardiac allograft vasculopathy (CAV) and play an immunomodulatory role. We studied the effect of statins on cardiac allograft survival at the National Taiwan University Hospital (NTUH). MATERIALS AND METHODS We retrospectively reviewed the patients undergoing heart transplantation at NTUH in the last 6 years. After transplantation, all patients received biochemical monitoring every month and echocardiographic examination regularly at NTUH. Protocol biopsy was performed in all except 18 pediatric patients. All patients received immunosuppressants, including tacrolimus or cyclosporine, everolimus or mycophenolate acid, and prednisolone. They were divided into statin and nonstatin groups according to whether or not a statin was taken. RESULTS At NTUH, from 2007 to 2012, 168 heart transplantations were performed. The ages of the patients ranged from 6 to 74 years old with male predominance. The etiology was mainly dilated cardiomyopathy (52.4%) and ischemic cardiomyopathy (39.3%), including 7 retransplantations from severe CAV with heart failure. Twenty-three patients (17%) suffered from acute rejection. The overall 1-year actuarial survival rate was 86% ± 2% and the 5-year survival rate was 79% ± 3%. Seventy-eight patients (57.4%) took statins and the statin group has a better 5-year survival rate and freedom from cardiac death survival rate (P < .01). CONCLUSION Our study showed that the use of statins after transplantation was associated with better survival.
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Affiliation(s)
- C-M Luo
- Department of Surgery, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan
| | - N-K Chou
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - N-H Chi
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Y-S Chen
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - H-Y Yu
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - C-H Chang
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - C-H Wang
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - C-I Tsao
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - S-S Wang
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
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30
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Interplay of coronary angiography and intravascular ultrasound in predicting long-term outcomes after heart transplantation. J Heart Lung Transplant 2015; 34:1146-53. [PMID: 25843518 DOI: 10.1016/j.healun.2015.01.990] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2014] [Revised: 12/30/2014] [Accepted: 01/31/2015] [Indexed: 10/24/2022] Open
Abstract
BACKGROUND Cardiac allograft vasculopathy (CAV) remains the major cause of late graft-related death after heart transplantation (HT). Identification of patients at risk of cardiovascular events has relevant implications in appropriately guiding resources and intensity of follow-up. In this context, the prognostic relevance of serial coronary imaging long-term after HT is unexplored. METHODS Recipients with intravascular ultrasound (IVUS) and coronary angiography performed 1 and 5 years after HT were monitored for subsequent 1 to 10 years to analyze the association of serial coronary imaging with cardiovascular death and major cardiovascular events (MACEs). RESULTS Included were 131 patients. The MACE incidence was 31.8 per 1,000 patient-years, and cardiovascular mortality was 17.4 per 1,000 patient-years. Progression of coronary lesions detected by angiography and changes in IVUS-defined parameters, including an increase in maximal intimal thickness (MIT) ≥0.35 mm and vascular remodeling, predicted MACE occurrence. However, only MIT change ≥0.35 mm also predicted cardiovascular mortality. Among patients with normal or stable angiography, an MIT change ≥0.35 mm identified those with a significantly higher MACE rate (80 vs 13 events/1,000 patient-years). Worsening metabolic parameters appeared associated with the increasing severity of CAV development. CONCLUSIONS Combined imaging analysis of progression of angiographic lesions and IVUS-detected MIT between 1 and 5 years post-HT allows discriminating patients at high, intermediate, and low risk for adverse long-term cardiovascular outcomes. The metabolic syndrome milieu is confirmed as a key risk factor for long-term CAV progression and adverse prognosis.
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32
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Sadat K, Morsy M, Khalife WI. Acute heart transplant graft failure in association with hyperosmolar hyperglycemia state. J Card Surg 2014; 29:737-9. [PMID: 25041938 DOI: 10.1111/jocs.12408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
We report a 38-year-old male with end-stage ischemic cardiomyopathy requiring left ventricular assist device placement, followed by orthotopic heart transplantation, who presented 18 months post-orthotopic heart transplant with acute graft failure with estimated left ventricular ejection fraction of 5% to 10%, in association with a glucose level of 550 mg/dL, and hemoglobin A1C of 13.8% and a negative pathology for a graft cellular and humoral rejection and no vasculaopthy. His left ventricular ejection fraction improved significantly to 40% to 45% within three days of optimal glucose control.
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Affiliation(s)
- Kamel Sadat
- Division of Cardiovascular Disease, University of Texas Medical Branch, Galveston, Texas
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Vecchiati A, Tellatin S, Angelini A, Iliceto S, Tona F. Coronary microvasculopathy in heart transplantation: Consequences and therapeutic implications. World J Transplant 2014; 4:93-101. [PMID: 25032098 PMCID: PMC4094955 DOI: 10.5500/wjt.v4.i2.93] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2013] [Revised: 01/11/2014] [Accepted: 03/12/2014] [Indexed: 02/05/2023] Open
Abstract
Despite the progress made in the prevention and treatment of rejection of the transplanted heart, cardiac allograft vasculopathy (CAV) remains the main cause of death in late survival transplanted patients. CAV consists of a progressive diffuse intimal hyperplasia and the proliferation of vascular smooth muscle cells, ending in wall thickening of epicardial vessels, intramyocardial arteries (50-20 μm), arterioles (20-10 μm), and capillaries (< 10 μm). The etiology of CAV remains unclear; both immunologic and non-immunologic mechanisms contribute to endothelial damage with a sustained inflammatory response. The immunological factors involved are Human Leukocyte Antigen compatibility between donor and recipient, alloreactive T cells and the humoral immune system. The non-immunological factors are older donor age, ischemia-reperfusion time, hyperlipidemia and CMV infections. Diagnostic techniques that are able to assess microvascular function are lacking. Intravascular ultrasound and fractional flow reserve, when performed during coronary angiography, are able to detect epicardial coronary artery disease but are not sensitive enough to assess microvascular changes. Some authors have proposed an index of microcirculatory resistance during maximal hyperemia, which is calculated by dividing pressure by flow (distal pressure multiplied by the hyperemic mean transit time). Non-invasive methods to assess coronary physiology are stress echocardiography, coronary flow reserve by transthoracic Doppler echocardiography, single photon emission computed tomography, and perfusion cardiac magnetic resonance. In this review, we intend to analyze the mechanisms, consequences and therapeutic implications of microvascular dysfunction, including an extended citation of relevant literature data.
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Singh N, Jacobs F, Rader DJ, Vanhaecke J, Van Cleemput J, De Geest B. Impaired cholesterol efflux capacity and vasculoprotective function of high-density lipoprotein in heart transplant recipients. J Heart Lung Transplant 2014; 33:499-506. [PMID: 24630408 DOI: 10.1016/j.healun.2014.01.859] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2013] [Revised: 12/19/2013] [Accepted: 01/16/2014] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND High-density lipoprotein (HDL) metabolism is significantly altered in heart transplant recipients. We hypothesized that HDL function may be impaired in these patients. METHODS Fifty-two patients undergoing coronary angiography between 5 and 15 years after heart transplantation were recruited in this cross-sectional study. Cholesterol efflux capacity of apolipoprotein B-depleted plasma was analyzed using a validated assay. The vasculoprotective function of HDL was studied by means of an endothelial progenitor cell migration assay. RESULTS HDL cholesterol levels were similar in heart transplant patients compared with healthy controls. However, normalized cholesterol efflux and vasculoprotective function were reduced by 24.1% (p < 0.001) and 27.0% (p < 0.01), respectively, in heart transplant recipients compared with healthy controls. HDL function was similar in patients with and without cardiac allograft vasculopathy (CAV) and was not related to C-reactive protein (CRP) levels. An interaction effect (p = 0.0584) was observed between etiology of heart failure before transplantation and steroid use as factors of HDL cholesterol levels. Lower HDL cholesterol levels occurred in patients with prior ischemic cardiomyopathy who were not taking steroids. However, HDL function was independent of the etiology of heart failure before transplantation and steroid use. The percentage of patients with a CRP level ≥6 mg/liter was 3.92-fold (p < 0.01) higher in patients with CAV than in patients without CAV. CONCLUSIONS HDL function is impaired in heart transplant recipients, but it is unrelated to CAV status. The proportion of patients with a CRP level ≥6 mg/liter is prominently higher in CAV-positive patients.
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Affiliation(s)
- Neha Singh
- Centre for Molecular and Vascular Biology, Department of Cardiovascular Sciences, Catholic University of Leuven, Leuven, Belgium
| | - Frank Jacobs
- Centre for Molecular and Vascular Biology, Department of Cardiovascular Sciences, Catholic University of Leuven, Leuven, Belgium
| | - Daniel J Rader
- Institute for Translational Medicine and Therapeutics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Johan Vanhaecke
- Division of Cardiology, Department of Cardiovascular Sciences, Catholic University of Leuven, Leuven, Belgium
| | - Johan Van Cleemput
- Division of Cardiology, Department of Cardiovascular Sciences, Catholic University of Leuven, Leuven, Belgium
| | - Bart De Geest
- Centre for Molecular and Vascular Biology, Department of Cardiovascular Sciences, Catholic University of Leuven, Leuven, Belgium.
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Lei J, Vodovotz Y, Tzeng E, Billiar TR. Nitric oxide, a protective molecule in the cardiovascular system. Nitric Oxide 2013; 35:175-85. [DOI: 10.1016/j.niox.2013.09.004] [Citation(s) in RCA: 123] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2013] [Revised: 09/02/2013] [Accepted: 09/24/2013] [Indexed: 12/19/2022]
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Martínez-Dolz L, Sánchez-Lázaro IJ, Almenar-Bonet L, Portolés M, Rivera M, Salvador A, Montero JA. Metabolic syndrome in heart transplantation: impact on survival and renal function. Transpl Int 2013; 26:910-8. [DOI: 10.1111/tri.12149] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2013] [Revised: 04/06/2013] [Accepted: 06/23/2013] [Indexed: 01/14/2023]
Affiliation(s)
- Luis Martínez-Dolz
- Heart Failure and Transplant Unit; Department of Cardiology; La Fe University Hospital; Valencia; Spain
| | - Ignacio J. Sánchez-Lázaro
- Heart Failure and Transplant Unit; Department of Cardiology; La Fe University Hospital; Valencia; Spain
| | - Luis Almenar-Bonet
- Heart Failure and Transplant Unit; Department of Cardiology; La Fe University Hospital; Valencia; Spain
| | - Manuel Portolés
- Center for Investigation; La Fe University Hospital; Valencia; Spain
| | - Miguel Rivera
- Center for Investigation; La Fe University Hospital; Valencia; Spain
| | - Antonio Salvador
- Heart Failure and Transplant Unit; Department of Cardiology; La Fe University Hospital; Valencia; Spain
| | - Jose Anastasio Montero
- Heart Failure and Transplant Unit; Department of Cardiology; La Fe University Hospital; Valencia; Spain
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Influence of Metabolic Syndrome on Development of Cardiac Allograft Vasculopathy in the Transplanted Heart. Transplantation 2012; 93:106-11. [DOI: 10.1097/tp.0b013e3182398058] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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Räkel A, Karelis AD. New-onset diabetes after transplantation: risk factors and clinical impact. DIABETES & METABOLISM 2011; 37:1-14. [PMID: 21295510 DOI: 10.1016/j.diabet.2010.09.003] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/05/2010] [Revised: 09/17/2010] [Accepted: 09/21/2010] [Indexed: 02/06/2023]
Abstract
With improvements in patient and graft survival, increasing attention has been placed on complications that contribute to long-term patient morbidity and mortality. New-onset diabetes after transplantation (NODAT) is a common complication of solid-organ transplantation, and is a strong predictor of graft failure and cardiovascular mortality in the transplant population. Risk factors for NODAT in transplant recipients are similar to those in non-transplant patients, but transplant-specific risk factors such as hepatitis C (HCV) infection, corticosteroids and calcineurin inhibitors play a dominant role in NODAT pathogenesis. Management of NODAT is similar to type 2 diabetes management in the general population. However, adjusting the immunosuppressant regimen to improve glucose tolerance must be weighed against the risk of allograft rejection. Lifestyle modification is currently the strategy with the least risk and the most benefit.
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Affiliation(s)
- A Räkel
- Department of Medicine, hôpital Saint-Luc, centre de recherche, centre hospitalier, University of Montreal, René-Lévesque-Est, Québec, Canada.
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Lim J, Kim S, Ke S, Cho B. The Prevalence of Obesity, Abdominal Obesity and Metabolic Syndrome among Elderly in General Population. Korean J Fam Med 2011. [DOI: 10.4082/kjfm.2011.32.2.128] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Affiliation(s)
- Juwon Lim
- Department of Family Medicine, Seoul National University Hospital, Seoul, Korea
| | - Soyeun Kim
- Department of Family Medicine, Seoul National University Hospital, Seoul, Korea
| | - Soshin Ke
- Department of Family Medicine, Seoul National University Hospital, Seoul, Korea
| | - Belong Cho
- Department of Family Medicine, Seoul National University Hospital, Seoul, Korea
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Gong W, Yang Z, Ye W, Du Y, Lu B, Wang M, Li Q, Zhang W, Pan Y, Feng X, Zhou W, Zhang Y, Wen J, Yang Z, Yang Y, Zhu X, Hu R. The Association of Dysglycaemia and Cardiovascular Disease in Patients with Metabolic Syndrome. J Int Med Res 2009; 37:1486-92. [PMID: 19930855 DOI: 10.1177/147323000903700525] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
The objective of this study was to investigate the relationship between increased prevalence of cardiovascular disease and glucose regulation status in Chinese patients with metabolic syndrome (MetS). All patients underwent an oral glucose tolerance test (2-h post-load plasma glucose) to determine their glucose regulation status and had their brachial–ankle pulse wave velocity (baPWV) measured. Of the 590 patients included in the study, 115 (19.5%) had normal glucose tolerance, 114 (19.3%) had impaired fasting glucose (IFG) alone, 38 (6.4%) had impaired glucose tolerance (IGT) alone, 197 (33.4%) had diabetes mellitus and 126 (21.4%) had combined glucose intolerance (CGI; IFG plus IGT). Patients with diabetes mellitus had a significantly higher baPWV compared with all other groups and patients with CGI had a significantly higher baPWW compared with patients with IFG. Dysglycaemia was common in patients with MetS. An increased prevalence of cardiovascular disease in patients with MetS was related to their glucose regulation status.
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Affiliation(s)
- W Gong
- Department of Endocrinology and Metabolism, HuaShan Hospital, Institute of Endocrinology and Diabetology at Fudan University, Shanghai, China
| | - Z Yang
- Department of Endocrinology and Metabolism, HuaShan Hospital, Institute of Endocrinology and Diabetology at Fudan University, Shanghai, China
| | - W Ye
- Department of Endocrinology and Metabolism, HuaShan Hospital, Institute of Endocrinology and Diabetology at Fudan University, Shanghai, China
| | - Y Du
- Department of Endocrinology and Metabolism, HuaShan Hospital, Institute of Endocrinology and Diabetology at Fudan University, Shanghai, China
| | - B Lu
- Department of Endocrinology and Metabolism, HuaShan Hospital, Institute of Endocrinology and Diabetology at Fudan University, Shanghai, China
| | - M Wang
- Department of Endocrinology and Metabolism, HuaShan Hospital, Institute of Endocrinology and Diabetology at Fudan University, Shanghai, China
| | - Q Li
- Department of Endocrinology and Metabolism, HuaShan Hospital, Institute of Endocrinology and Diabetology at Fudan University, Shanghai, China
| | - W Zhang
- Department of Endocrinology and Metabolism, HuaShan Hospital, Institute of Endocrinology and Diabetology at Fudan University, Shanghai, China
| | - Y Pan
- Department of Endocrinology and Metabolism, HuaShan Hospital, Institute of Endocrinology and Diabetology at Fudan University, Shanghai, China
| | - X Feng
- Department of Endocrinology and Metabolism, HuaShan Hospital, Institute of Endocrinology and Diabetology at Fudan University, Shanghai, China
| | - W Zhou
- Department of Endocrinology and Metabolism, HuaShan Hospital, Institute of Endocrinology and Diabetology at Fudan University, Shanghai, China
| | - Y Zhang
- Department of Endocrinology and Metabolism, HuaShan Hospital, Institute of Endocrinology and Diabetology at Fudan University, Shanghai, China
| | - J Wen
- Department of Endocrinology and Metabolism, HuaShan Hospital, Institute of Endocrinology and Diabetology at Fudan University, Shanghai, China
| | - Z Yang
- Department of Endocrinology and Metabolism, HuaShan Hospital, Institute of Endocrinology and Diabetology at Fudan University, Shanghai, China
| | - Y Yang
- Department of Endocrinology and Metabolism, HuaShan Hospital, Institute of Endocrinology and Diabetology at Fudan University, Shanghai, China
| | - X Zhu
- Department of Endocrinology and Metabolism, HuaShan Hospital, Institute of Endocrinology and Diabetology at Fudan University, Shanghai, China
| | - R Hu
- Department of Endocrinology and Metabolism, HuaShan Hospital, Institute of Endocrinology and Diabetology at Fudan University, Shanghai, China
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Abstract
The availability of new immunosuppressive drugs has led to improvement in outcome for transplanted patients, but these drugs have also led to the increase of metabolic abnormalities, such as dyslipidemia and hyperglycemia, which can affect graft and patient outcome. Posttransplant diabetes mellitus (PTDM) or new-onset diabetes after transplantation is defined as the onset of diabetes in previously nondiabetic transplant recipients. Several clinical studies have demonstrated the involvement of PTDM in death due to infectious and cardiovascular disease. This article reviews recent concepts on pathophysiology, diagnosis, and treatment of PTDM.
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Zakliczynski M, Nozynski J, Konecka-Mrowka D, Krynicka-Mazurek A, Swierad M, Maruszewski M, Przybylski R, Zembala M. Vascular abnormalities and cardiomyocyte lipofuscin deposits in endomyocardial biopsy specimens of heart transplant recipients: Are they related to the development of cardiac allograft vasculopathy? J Thorac Cardiovasc Surg 2009; 138:215-21, 221.e1-3. [DOI: 10.1016/j.jtcvs.2009.02.040] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2008] [Revised: 02/10/2009] [Accepted: 02/22/2009] [Indexed: 01/03/2023]
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Luknar M, Goncalvesova E, Lesny P, Fabian J. Telmisartan and metabolic syndrome after heart transplantation. Clin Transplant 2009; 24:36-9. [PMID: 19222503 DOI: 10.1111/j.1399-0012.2009.00979.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
INTRODUCTION Metabolic syndrome (MS) is a cardiovascular risk predictor. Prevalence of MS after heart transplantation (HTx) is high. Recent data suggest a positive metabolic effect of telmisartan. AIM To describe the influence of telmisartan on lipid and glycide metabolism in MS after HTx. METHODS Fifteen patients aged 55+/-12 yr, 88+/-25 months after HTx with MS receiving statins were followed. The reason for telmisartan administration was arterial hypertension with either drug intolerance or poor control. Body mass index (BMI), waist circumference, total cholesterol, low density lipoprotein LDL-cholesterol, high density lipoprotein-cholesterol, triglycerides, C-reactive protein (CRP), fasting glucose, immunoreactive insulin (IRI), C-peptide and the homeostasis model assessment (HOMA) index were determined. Ambulatory blood pressure monitoring was performed. After initial evaluation, telmisartan 80 mg was started. After 20 +/- 5 wk follow-up, identical parameters were measured. Statistical significance was evaluated using Student's t-test. RESULTS BMI, waist circumference, systolic and diastolic blood pressures, serum lipids and CRP remained unchanged after telmisartan. Significant reduction in fasting glucose (6.7 vs. 5.6 mmol/L, p < 0.02), IRI (8.8 vs. 8.5 U/mL p = 0.05), HOMA (7.3 vs. 5.8 mmol/L x muU/mL, p < 0.05) and C-peptide (4.0 vs. 3.3 ng/mL, p < 0.02) was found. CONCLUSIONS Telmisartan had a positive impact on insulin sensitivity parameters (fasting glucose, IRI, C-peptide and HOMA) in this population. No effect on obesity, serum lipids and systemic inflammation was observed.
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Affiliation(s)
- Milan Luknar
- Heart Failure and Transplant Department, National Institute of Cardiovascular Disease, Bratislava, Slovakia.
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Ambrosi P, Oddoze C, Nicolay A, Penet-Lorec AM, Riberi A, Métras D, Portugal H, Habib G. Plasma adiponectin in heart transplant recipients. Clin Transplant 2009; 23:83-8. [DOI: 10.1111/j.1399-0012.2008.00905.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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Abstract
New-onset diabetes mellitus is a common complication of solid organ transplantation and is likely to become even more common with the current epidemic of obesity in some countries. It has become clear that both new-onset diabetes and prediabetic states (impaired fasting glucose and impaired glucose tolerance) negatively influence graft and patient survival after transplantation. This observation forms the basis for recommending meticulous screening for glucose intolerance before and after transplantation. Although a number of clinical factors including age, weight, ethnicity, family history, and infection with hepatitis C are closely associated with the new-onset diabetes mellitus, immunosuppression with corticosteroids, calcineurin inhibitors and possibly sirolimus plays a dominant role in its pathogenesis. Management of new-onset diabetes after transplantation generally conforms to the guidelines for treatment of type 2 diabetes mellitus in the general population. However, further studies are needed to determine the optimal immunosuppressive regimens for patients with this disorder.
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Affiliation(s)
- Kenneth A Bodziak
- Department of Medicine, Division of Nephrology and Hypertension, Case Western Reserve University and the Transplantation Service, University Hospitals Case Medical Center, Cleveland, OH 44106, USA
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Abstract
As patient survival after solid organ transplantation continues to improve, comorbidites associated with chronic hyperglycemia will assume increasing importance in limiting outcomes and quality of life. New-onset diabetes mellitus commonly occurs in the posttransplant setting and is associated with multiple complications including graft loss, cardiovascular disease, infection, and death. Furthermore, recent studies have begun to highlight the very high posttransplant prevalence and the significant cardiovascular implications of the prediabetic states of impaired fasting glucose and impaired glucose tolerance, indicating that the overall burden of transplantation-associated hyperglycemia is far greater than previously appreciated. Shared and distinct pathogenic factors and clinical repercussions exist among the organ-specific transplant scenarios. Diabetogenic immunosuppressive agents are common to all organ transplant settings, whereas glucose regulation is also strained by the restoration of failed hepatic and renal function. The atherogenic properties of hyperglycemia are particularly significant in the kidney transplant population, which has a marked predisposition to cardiovascular disease, whereas accelerated cardiac allograft vasculopathy and liver fibrosis have been associated with hyperglycemia in the heart and liver transplant settings, respectively. Aggressive screening will effectively detect transplant-associated hyperglycemia, whereas risk factor modification, lifestyle intervention and, where appropriate, drug therapy, may decrease its impact. Topics of future investigation should include the use of emerging diabetes therapies and avenues for the prevention and reversal of transplant-associated hyperglycemia.
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Affiliation(s)
- Roy D Bloom
- Renal Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
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Follow-up Study on the Utility of von Willebrand Factor Levels in the Diagnosis of Cardiac Allograft Vasculopathy. J Heart Lung Transplant 2008; 27:760-6. [DOI: 10.1016/j.healun.2008.04.010] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2008] [Revised: 04/13/2008] [Accepted: 04/21/2008] [Indexed: 11/20/2022] Open
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Long-term effect of folic acid therapy in heart transplant recipients: follow-up analysis of a randomized study. Transplantation 2008; 85:1146-50. [PMID: 18431235 DOI: 10.1097/tp.0b013e31816b2602] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Folic acid therapy reduces homocysteine plasma levels, which seem to influence occurrence of cardiac allograft vasculopathy, but its effect on medium- or long-term prognosis after heart transplantation is unknown. METHODS We analyzed 7-year outcome of 51 recipients randomized to receive 15 mg/day of methyltertrahydrofolate for 1 year after heart transplantation or standard therapy alone (originally, for intravascular ultrasound study of short-term cardiac allograft vasculopathy progression); recipients were observed for a further 5 to 6 years. RESULTS Overall, 13 deaths occurred (six oncologic, five cardiovascular, two infective). Estimated 7-year survival was better in recipients randomized to folate (88%+/-6% vs. 61%+/-9%, P=0.04). After adjusting for age, pretransplant coronary artery disease, and hyperhomocysteinemia, posttransplant folic acid therapy was associated with lower mortality (relative risk [RR] 0.53, 95% confidence interval [CI] 0.25-0.97; P=0.036), apparently driven by reductions in both cancer-related and cardiovascular causes. Reduced mortality was marked in a high-risk subgroup comprising older recipients and patients transplanted because of coronary artery disease (RR 0.43, 95% CI 0.17-0.85) but not in the lower-risk subgroup (RR 1.11, 95% CI 0.22-5.61). CONCLUSIONS Although further studies are needed, it seems reasonable to suggest folate therapy to heart transplant recipients. It is possible that properties other than homocysteine reduction may provide antitumoral benefits.
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Risk Profile for Cardiovascular Morbidity and Mortality After Lung Transplantation. Nurs Clin North Am 2008; 43:37-53; vi. [DOI: 10.1016/j.cnur.2007.10.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Aguero J, Almenar L, Martínez-Dolz L, Moro JA, Rueda J, Raso R, Chamorro C, Sanchez JM, Salvador A. Influence of immunosuppressive regimens on short-term morbidity and mortality in heart transplantation. Clin Transplant 2008; 22:98-106. [PMID: 18217910 DOI: 10.1111/j.1399-0012.2007.00751.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
BACKGROUND The goal of immunosuppressive therapy in heart transplantation is to maximize safety and efficacy while minimizing morbidity and mortality. We now have numerous drug combinations, but few have been compared with each other. AIM To compare various immunosuppressive regimens assessing morbidity and mortality at one yr. METHODS A total of 351 patients transplanted between 1989 and 2005 were included and grouped by immunosuppressive regimen into group 1 (n = 52): Muronomab (OKT3) 10 d, cyclosporine (CSA), azathioprine (AZA), steroids; group 2 (n = 193): OKT3 seven d, CSA, AZA, steroids; group 3 (n = 22): OKT3 seven d, CSA, mycophenolate mofetil (MMF), steroids; and group 4 (n = 84): interleukin-2 antagonists (IL-2), CSA, MMF, steroids. RESULTS The incidence of acute graft failure and treated rejection was similar between groups (17% and 78% respectively). We found a statistically significant difference in the incidence of infections (p < 0.001), renal dysfunction (p = 0.011) and in diabetes mellitus (p = 0.023). There were no differences in survival at 30 d (97%), but differences were found at one yr (p = 0.011). The multivariate analysis showed a strong association between mortality and infection (p = 0.001) and between survival and the group 4 regimen (p < 0.001). CONCLUSION There are differences in survival at one yr of heart transplant patients depending on the immunosuppressive regimen used. The best combination was induction with IL-2 antagonists, followed by CSA, MMF and steroids.
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Affiliation(s)
- Jaime Aguero
- Heart Failure and Transplant Unit, Cardiology Department, La Fe University Hospital, Valencia, Spain.
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