|
1
|
Żera T, Paleczny B, Siński M, Conde SV, Narkiewicz K, Ponikowski P, Paton JF, Niewiński P. Translating physiology of the arterial chemoreflex into novel therapeutic interventions targeting carotid bodies in cardiometabolic disorders. J Physiol 2025; 603:2487-2516. [PMID: 40186613 PMCID: PMC12072261 DOI: 10.1113/jp285081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Accepted: 03/10/2025] [Indexed: 04/07/2025] Open
Abstract
This review resulted from a conference on the pathological role of arterial chemoreflex and carotid bodies in cardiometabolic diseases held at the 27th Congress of the Polish Cardiac Society in September 2023 in Poznan, Poland. It reflects the contribution of Polish researchers and their international collaborations, which have been fundamental in the development of the field. Aberrant activity of the carotid bodies leads to both high tonicity and increased sensitivity of the arterial chemoreflex with resultant sympathoexcitation in chronic heart failure, resistant hypertension and obstructive sleep apnoea. This observation has led to several successful attempts of removing or denervating the carotid bodies as a therapeutic option in humans. Regrettably, such interventions are accompanied by serious respiratory and acid-base balance side-effects. Rather than a single stereotyped reaction, arterial chemoreflex comprises an integrative multi-system response to a variety of stimulants and its specific reflex components may be individually conveyed at varying intensities. Recent research has revealed that carotid bodies express diverse receptors, synthesize a cocktail of mediators, and respond to a plethora of metabolic, hormonal and autonomic nervous stimuli. This state-of-the-art summary discusses exciting new discoveries regarding GLP-1 receptors, purinergic receptors, the glutamate-GABA system, efferent innervation and regulation of blood flow in the carotid body and how they open new avenues for novel pharmacological treatments selectively targeting specific receptors, mediators and neural pathways to correct distinct responses of the carotid body-evoked arterial chemoreflex in cardiometabolic diseases. The carotid body offers novel and advantageous therapeutic opportunities for future consideration by trialists.
Collapse
Affiliation(s)
- Tymoteusz Żera
- Department of Experimental and Clinical PhysiologyMedical University of WarsawWarsawPoland
| | - Bartłomiej Paleczny
- Department of Physiology and PathophysiologyWroclaw Medical UniversityWroclawPoland
| | - Maciej Siński
- Department of Internal Medicine, Hypertension and Vascular DiseasesMedical University of WarsawWarsawPoland
| | - Sílvia V. Conde
- iNOVA4Health, NOVA Medical School, Faculdade de Ciências MédicasUniversidade NOVA de LisboaLisbonPortugal
| | - Krzysztof Narkiewicz
- Department of Hypertension and DiabetologyMedical University of GdańskGdańskPoland
| | - Piotr Ponikowski
- Institute of Heart DiseasesWroclaw Medical UniversityWroclawPoland
| | - Julian F.R. Paton
- Manaaki Manawa – The Centre for Heart Research, Department of Physiology, Faculty of Medical & Health SciencesUniversity of AucklandAucklandNew Zealand
| | - Piotr Niewiński
- Institute of Heart DiseasesWroclaw Medical UniversityWroclawPoland
| |
Collapse
|
|
2
|
Kasai T, Kohno T, Shimizu W, Ando S, Joho S, Osada N, Kato M, Kario K, Shiina K, Tamura A, Yoshihisa A, Fukumoto Y, Takata Y, Yamauchi M, Shiota S, Chiba S, Terada J, Tonogi M, Suzuki K, Adachi T, Iwasaki Y, Naruse Y, Suda S, Misaka T, Tomita Y, Naito R, Goda A, Tokunou T, Sata M, Minamino T, Ide T, Chin K, Hagiwara N, Momomura S. JCS 2023 Guideline on Diagnosis and Treatment of Sleep Disordered Breathing in Cardiovascular Disease. Circ J 2024; 88:1865-1935. [PMID: 39183026 DOI: 10.1253/circj.cj-23-0489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/27/2024]
Affiliation(s)
- Takatoshi Kasai
- Division of School of Health Science, Department of Pathobiological Science and Technology, Faculty of Medicine, Tottori University
| | - Takashi Kohno
- Department of Cardiovascular Medicine, Kyorin University Faculty of Medicine
| | - Wataru Shimizu
- Department of Cardiovascular Medicine, Graduate School of Medicine, Nippon Medical School
| | - Shinichi Ando
- Sleep Medicine Center, Fukuokaken Saiseikai Futsukaichi Hospital
| | - Shuji Joho
- Second Department of Internal Medicine, University of Toyama
| | - Naohiko Osada
- Department of Cardiology, St. Marianna University School of Medicine
| | - Masahiko Kato
- Division of School of Health Science, Department of Pathobiological Science and Technology, Faculty of Medicine, Tottori University
| | - Kazuomi Kario
- Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine
| | | | | | - Akiomi Yoshihisa
- Department of Clinical Laboratory Sciences, Fukushima Medical University School of Health Science
- Department of Cardiovascular Medicine, Fukushima Medical University
| | - Yoshihiro Fukumoto
- Division of Cardiovascular Medicine, Department of Internal Medicine, Kurume University School of Medicine
| | | | - Motoo Yamauchi
- Department of Clinical Pathophysiology of Nursing and Department of Respiratory Medicine, Nara Medical University
| | - Satomi Shiota
- Department of Respiratory Medicine, Juntendo University Graduate School of Medicine
| | | | - Jiro Terada
- Department of Respiratory Medicine, Japanese Red Cross Narita Hospital
| | - Morio Tonogi
- 1st Depertment of Oral & Maxillofacial Surgery, Nihon Univercity School of Dentistry
| | | | - Taro Adachi
- Division of Cardiology, Department of Medicine, Showa University School of Medicine
| | - Yuki Iwasaki
- Department of Cardiovascular Medicine, Graduate School of Medicine, Nippon Medical School
| | - Yoshihisa Naruse
- Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine
| | - Shoko Suda
- Department of Cardiovascular Medicine, Juntendo University School of Medicine
| | - Tomofumi Misaka
- Department of Clinical Laboratory Sciences, Fukushima Medical University School of Health Science
- Department of Cardiovascular Medicine, Fukushima Medical University
| | | | - Ryo Naito
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine
| | - Ayumi Goda
- Department of Cardiovascular Medicine, Kyorin University Faculty of Medicine
| | - Tomotake Tokunou
- Division of Cardiology, Department of Medicine, Fukuoka Dental College
| | - Makoto Sata
- Department of Pulmonology and Infectious Diseases, National Cerebral and Cardiovascular Center
| | | | - Tomomi Ide
- Faculty of Medical Sciences, Kyushu University
| | - Kazuo Chin
- Graduate School of Medicine and Faculty of Medicine, Kyoto University
| | - Nobuhisa Hagiwara
- YUMINO Medical Corporation
- Department of Cardiology, Tokyo Women's Medical University
| | | |
Collapse
|
|
3
|
Díaz-Jara E, Pereyra K, Vicencio S, Olesen MA, Schwarz KG, Toledo C, Díaz HS, Quintanilla RA, Del Rio R. Superoxide dismutase 2 deficiency is associated with enhanced central chemoreception in mice: Implications for breathing regulation. Redox Biol 2024; 69:102992. [PMID: 38142585 PMCID: PMC10788617 DOI: 10.1016/j.redox.2023.102992] [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: 10/30/2023] [Accepted: 12/07/2023] [Indexed: 12/26/2023] Open
Abstract
AIMS In mammals, central chemoreception plays a crucial role in the regulation of breathing function in both health and disease conditions. Recently, a correlation between high levels of superoxide anion (O2.-) in the Retrotrapezoid nucleus (RTN), a main brain chemoreceptor area, and enhanced central chemoreception has been found in rodents. Interestingly, deficiency in superoxide dismutase 2 (SOD2) expression, a pivotal antioxidant enzyme, has been linked to the development/progression of several diseases. Despite, the contribution of SOD2 on O2.- regulation on central chemoreceptor function is unknown. Accordingly, we sought to determine the impact of partial deletion of SOD2 expression on i) O2.-accumulation in the RTN, ii) central ventilatory chemoreflex function, and iii) disordered-breathing. Finally, we study cellular localization of SOD2 in the RTN of healthy mice. METHODS Central chemoreflex drive and breathing function were assessed in freely moving heterozygous SOD2 knockout mice (SOD2+/- mice) and age-matched control wild type (WT) mice by whole-body plethysmography. O2.- levels were determined in RTN brainstem sections and brain isolated mitochondria, while SOD2 protein expression and tissue localization were determined by immunoblot, RNAseq and immunofluorescent staining, respectively. RESULTS Our results showed that SOD2+/- mice displayed reductions in SOD2 levels and high O2.- formation and mitochondrial dysfunction within the RTN compared to WT. Additionally, SOD2+/- mice displayed a heightened ventilatory response to hypercapnia and exhibited overt signs of altered breathing patterns. Both, RNAseq analysis and immunofluorescence co-localization studies showed that SOD2 expression was confined to RTN astrocytes but not to RTN chemoreceptor neurons. Finally, we found that SOD2+/- mice displayed alterations in RTN astrocyte morphology compared to RTN astrocytes from WT mice. INNOVATION & CONCLUSION These findings provide first evidence of the role of SOD2 in the regulation of O2.- levels in the RTN and its potential contribution on the regulation of central chemoreflex function. Our results suggest that reductions in the expression of SOD2 in the brain may contribute to increase O2.- levels in the RTN being the outcome a chronic surge in central chemoreflex drive and the development/maintenance of altered breathing patterns. Overall, dysregulation of SOD2 and the resulting increase in O2.- levels in brainstem respiratory areas can disrupt normal respiratory control mechanisms and contribute to breathing dysfunction seen in certain disease conditions characterized by high oxidative stress.
Collapse
Affiliation(s)
- Esteban Díaz-Jara
- Laboratory of Cardiorespiratory Control, Pontificia Universidad Católica de Chile, Santiago, Chile.
| | - Katherine Pereyra
- Laboratory of Cardiorespiratory Control, Pontificia Universidad Católica de Chile, Santiago, Chile.
| | - Sinay Vicencio
- Laboratory of Cardiorespiratory Control, Pontificia Universidad Católica de Chile, Santiago, Chile.
| | - Margrethe A Olesen
- Laboratory of Neurodegenerative Diseases, Universidad Autónoma de Chile, Santiago, Chile.
| | - Karla G Schwarz
- Laboratory of Cardiorespiratory Control, Pontificia Universidad Católica de Chile, Santiago, Chile.
| | - Camilo Toledo
- Laboratory of Cardiorespiratory Control, Pontificia Universidad Católica de Chile, Santiago, Chile; Institute of Physiology, Universidad Austral de Chile, Valdivia, Chile.
| | - Hugo S Díaz
- Laboratory of Cardiorespiratory Control, Pontificia Universidad Católica de Chile, Santiago, Chile.
| | - Rodrigo A Quintanilla
- Laboratory of Neurodegenerative Diseases, Universidad Autónoma de Chile, Santiago, Chile.
| | - Rodrigo Del Rio
- Laboratory of Cardiorespiratory Control, Pontificia Universidad Católica de Chile, Santiago, Chile; Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas, Chile; Department of Cell Biology and Physiology, School of Medicine, University of Kansas Medical Center, Kansas City, KS, United States.
| |
Collapse
|
|
4
|
Cunha G, Apostolo A, De Martino F, Salvioni E, Matavelli I, Agostoni P. Exercise oscillatory ventilation: the past, present, and future. Eur J Prev Cardiol 2023; 30:ii22-ii27. [PMID: 37819229 DOI: 10.1093/eurjpc/zwad205] [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: 01/11/2023] [Revised: 05/22/2023] [Accepted: 06/12/2023] [Indexed: 10/13/2023]
Abstract
Exercise oscillatory ventilation (EOV) is a fascinating event that can be appreciated in the cardiopulmonary exercise test and is characterized by a cyclic fluctuation of minute ventilation, tidal volume, oxygen uptake, carbon dioxide production, and end-tidal pressure for oxygen and carbon dioxide. Its mechanisms stem from a dysregulation of the normal control feedback of ventilation involving one or more of its components, namely, chemoreflex delay, chemoreflex gain, plant delay, and plant gain. In this review, we intend to breakdown therapeutic targets according to pathophysiology and revise the prognostic value of exercise oscillatory ventilation in the setting of heart failure and other diagnoses.
Collapse
Affiliation(s)
- Gonçalo Cunha
- Cardiology department, Hospital de Santa Cruz, Centro Hospitalar Lisboa Ocidental, Av. Prof. Dr. Reinaldo dos Santos, 2790-134 Carnaxide, Portugal
| | - Anna Apostolo
- Heart failure department, Centro Cardiologico Monzino, IRCCS, Milan, Italy
| | | | | | - Irene Matavelli
- Heart failure department, Centro Cardiologico Monzino, IRCCS, Milan, Italy
| | - Piergiuseppe Agostoni
- Heart failure department, Centro Cardiologico Monzino, IRCCS, Milan, Italy
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| |
Collapse
|
|
5
|
Tubek S, Niewinski P, Langner-Hetmanczuk A, Jura M, Kuliczkowski W, Reczuch K, Ponikowski P. The effects of P2Y 12 adenosine receptors' inhibitors on central and peripheral chemoreflexes. Front Physiol 2023; 14:1214893. [PMID: 37538377 PMCID: PMC10394699 DOI: 10.3389/fphys.2023.1214893] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Accepted: 06/30/2023] [Indexed: 08/05/2023] Open
Abstract
Introduction: The most common side effect of ticagrelor is dyspnea, which leads to premature withdrawal of this life-saving medication in 6.5% of patients. Increased chemoreceptors' sensitivity was suggested as a possible pathophysiological explanation of this phenomenon; however, the link between oversensitization of peripheral and/or central chemosensory areas and ticagrelor intake has not been conclusively proved. Methods: We measured peripheral chemoreceptors' sensitivity using hypoxic ventilatory response (HVR), central chemoreceptors' sensitivity using hypercapnic hyperoxic ventilatory response (HCVR), and dyspnea severity before and 4 ± 1 weeks following ticagrelor initiation in 11 subjects with chronic coronary syndrome undergoing percutaneous coronary intervention (PCI). The same tests were performed in 11 age-, sex-, and BMI-matched patients treated with clopidogrel. The study is registered at ClinicalTrials.com at NCT05080478. Results: Ticagrelor significantly increased both HVR (0.52 ± 0.46 vs. 0.84 ± 0.69 L min-1 %-1; p < 0.01) and HCVR (1.05 ± 0.64 vs. 1.75 ± 1.04 L min-1 mmHg-1; p < 0.01). The absolute change in HVR correlated with the change in HCVR. Clopidogrel administration did not significantly influence HVR (0.63 ± 0.32 vs. 0.58 ± 0.33 L min-1%-1; p = 0.53) and HCVR (1.22 ± 0.67 vs. 1.2 ± 0.64 L min-1 mmHg-1; p = 0.79). Drug-related dyspnea was reported by three subjects in the ticagrelor group and by none in the clopidogrel group. These patients were characterized by either high baseline HVR and HCVR or excessive increase in HVR following ticagrelor initiation. Discussion: Ticagrelor, contrary to clopidogrel, sensitizes both peripheral and central facets of chemodetection. Two potential mechanisms of ticagrelor-induced dyspnea have been identified: 1) high baseline HVR and HCVR or 2) excessive increase in HVR or HVR and HCVR. Whether other patterns of changes in chemosensitivities play a role in the pathogenesis of this phenomenon needs to be further investigated.
Collapse
Affiliation(s)
- Stanislaw Tubek
- Institute of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland
- Institute of Heart Diseases, University Hospital, Wroclaw, Poland
| | - Piotr Niewinski
- Institute of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland
- Institute of Heart Diseases, University Hospital, Wroclaw, Poland
| | - Anna Langner-Hetmanczuk
- Institute of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland
- Institute of Heart Diseases, University Hospital, Wroclaw, Poland
| | - Maksym Jura
- Institute of Heart Diseases, University Hospital, Wroclaw, Poland
- Department of Physiology, Wroclaw Medical University, Wroclaw, Poland
| | - Wiktor Kuliczkowski
- Institute of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland
- Institute of Heart Diseases, University Hospital, Wroclaw, Poland
| | - Krzysztof Reczuch
- Institute of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland
- Institute of Heart Diseases, University Hospital, Wroclaw, Poland
| | - Piotr Ponikowski
- Institute of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland
- Institute of Heart Diseases, University Hospital, Wroclaw, Poland
| |
Collapse
|
|
6
|
Magrì D, Palermo P, Salvioni E, Mapelli M, Gallo G, Vignati C, Mattavelli I, Gugliandolo P, Maruotti A, Di Loro PA, Fiori E, Sciomer S, Agostoni P. Influence of exertional oscillatory breathing and its temporal behavior in patients with heart failure and reduced ejection fraction. Int J Cardiol 2023:S0167-5273(23)00659-9. [PMID: 37164295 DOI: 10.1016/j.ijcard.2023.05.008] [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: 02/15/2023] [Revised: 04/12/2023] [Accepted: 05/05/2023] [Indexed: 05/12/2023]
Abstract
BACKGROUND Exertional oscillatory breathing (EOV) represents an emerging prognostic marker in heart failure (HF) patients, however little is known about EOV meaning with respect to its disappearance/persistence during cardiopulmonary exercise test (CPET). The present single-center study evaluated EOV clinical and prognostic impact in a large cohort of reduced ejection fraction HF patients (HFrEF) and, contextually, if a specific EOV temporal behavior might be an addictive risk predictor. METHODS AND RESULTS Data from 1.866 HFrEF patients on optimized medical therapy were analysed. The primary cardiovascular (CV) study end-point was cardiovascular death, heart transplantation or LV assistance device (LVAD) implantation at 5-years. For completeness a secondary end-point of total mortality at 5- years was also explored. EOV presence was identified in 251 patients (13%): 142 characterized by EOV early cessation (Group A) and 109 by EOV persistence during the whole CPET (Group B). The entire EOV Group showed worse clinical and functional status than NoEOV Group (n = 1.615) and, within the EOV Group, Group B was characterized by a more severe HF. At CV survival analysis, EOV patients showed a poorer outcome than the NoEOV Group (events 27.1% versus 13.1%, p < 0.001) both unpolished and after matching for main confounders. Instead, no significant differences were found between EOV Group A and B with respect to CV outcome. Conversely the analysis for total mortality failed to be significant. CONCLUSIONS Our analysis, albeit retrospective, supports the inclusion of EOV into a CPET-centered clinical and prognostic evaluation of the HFrEF patients. EOV characterizes per se a more advanced HFrEF stage with an unfavorable CV outcome. However, the EOV persistence, albeit suggestive of a more severe HF, does not emerge as a further prognostic marker.
Collapse
Affiliation(s)
- Damiano Magrì
- Department of Clinical and Molecular Medicine, Azienda Ospedaliera Sant'Andrea, "Sapienza" University, Rome, Italy
| | | | | | - Massimo Mapelli
- Centro Cardiologico Monzino, IRCCS, Milan, Italy.; Dept. of Clinical sciences and Community health, Cardiovascular Section, University of Milano, Milan, Italy
| | - Giovanna Gallo
- Department of Clinical and Molecular Medicine, Azienda Ospedaliera Sant'Andrea, "Sapienza" University, Rome, Italy
| | | | | | | | - Antonello Maruotti
- Dipartimento di Giurisprudenza, Economia, Politica e Lingue Moderne - Libera Università Maria Ss Assunta; Department of Mathematics, University of Bergen, Norway; School of Computing, University of Portsmouth, United Kingdom
| | | | - Emiliano Fiori
- Department of Clinical and Molecular Medicine, Azienda Ospedaliera Sant'Andrea, "Sapienza" University, Rome, Italy
| | - Susanna Sciomer
- Dipartimento di Scienze Cardiovascolari, Respiratorie, Nefrologiche, Anestesiologiche e Geriatriche, "Sapienza" University, Rome, Italy
| | - Piergiuseppe Agostoni
- Centro Cardiologico Monzino, IRCCS, Milan, Italy.; Dept. of Clinical sciences and Community health, Cardiovascular Section, University of Milano, Milan, Italy..
| |
Collapse
|
|
7
|
Respiratory patterns and baroreflex function in heart failure. Sci Rep 2023; 13:2220. [PMID: 36755066 PMCID: PMC9908869 DOI: 10.1038/s41598-023-29271-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Accepted: 02/01/2023] [Indexed: 02/10/2023] Open
Abstract
Little is known on the effects of respiratory patterns on baroreflex function in heart failure (HF). Patients with HF (n = 30, age 61.6 ± 10 years, mean ± SD) and healthy controls (CNT, n = 10, age 58.9 ± 5.6 years) having their R-R interval (RRI, EKG), systolic arterial blood pressure (SBP, Finapres) and respiratory signal (RSP, Respitrace) monitored, were subjected to three recording sessions: free-breathing, fast- (≥ 12 bpm) and slow- (6 bpm) paced breathing. Baroreflex sensitivity (BRS) and power spectra of RRI, SBP, and RSP signals were calculated. During free-breathing, compared to CNT, HF patients showed a significantly greater modulation of respiratory volumes in the very-low-frequency (< 0.04 Hz) range and their BRS was not significantly different from that of CNT. During fast-paced breathing, when very-low-frequency modulations of respiration were reduced, BRS of HF patients was significantly lower than that of CNT and lower than during free breathing. During slow-paced breathing, BRS became again significantly higher than during fast breathing. In conclusion: (1) in free-breathing HF patients is present a greater modulation of respiratory volumes in the very-low-frequency range; (2) in HF patients modulation of respiration in the very-low and low frequency (around 0.1 Hz) ranges contributes to preserve baroreflex-mediated control of heart rate.
Collapse
|
|
8
|
Cunha GJL, Maltês S, Rocha BML, Nina D, Aguiar C, Andrade MJ, Moreno L, Durazzo A, Mendes M, Agostoni P. Beyond exercise oscillatory ventilations: the prognostic impact of loop gain in heart failure. Eur J Prev Cardiol 2023; 30:zwad021. [PMID: 36707994 DOI: 10.1093/eurjpc/zwad021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Revised: 01/07/2023] [Accepted: 01/24/2023] [Indexed: 01/29/2023]
Abstract
Exercise oscillatory ventilation (EOV) is a strong prognostic marker in patients with heart failure (HF) and left ventricular (LV) dysfunction. This phenomenon can be explained through a single quantitative measurement of ventilatory instability, the loop gain. Therefore, we aimed to evaluate whether loop gain could be a better tool than subjective EOV evaluation to identify HF patients with a higher risk of major cardiovascular complications. This was a single-center retrospective study that included patients with left ventricular ejection fraction (LVEF) ≤ 50% consecutively referred for cardiopulmonary exercise testing (CPET) from 2016-2020. Loop gain was measured through computational evaluation of the minute ventilation graph. Of the 250 patients included, the 66 that presented EOV also had higher values of loop gain, when compared to patients without EOV. Those with both EOV and higher loop gain had more severe HF, with higher NT-proBNP and VE/VCO2 slope as well as lower peak VO2 and LVEF. On multivariable analysis, loop gain was strongly correlated with the composite endpoint of cardiovascular death, urgent heart transplantation, urgent left ventricular assist device implantation or HF hospitalization, even after correcting for peak VO2, LVEF, VE/VCO2 slope and NT-proBNP. Presence of EOV was not prognostically significant in this analysis. Loop gain is an objective parameter that quantifies ventilatory instability and showed to have a strong prognostic value in a cohort of patients with HF and LVEF ≤ 50%, outperforming the classification of EOV.
Collapse
Affiliation(s)
- Gonçalo J L Cunha
- Hospital de Santa Cruz, Centro Hospitalar Lisboa Ocidental, Carnaxide, Portugal
| | - Sérgio Maltês
- Hospital de Santa Cruz, Centro Hospitalar Lisboa Ocidental, Carnaxide, Portugal
| | - Bruno M L Rocha
- Hospital de Santa Cruz, Centro Hospitalar Lisboa Ocidental, Carnaxide, Portugal
| | | | - Carlos Aguiar
- Hospital de Santa Cruz, Centro Hospitalar Lisboa Ocidental, Carnaxide, Portugal
| | - Maria J Andrade
- Hospital de Santa Cruz, Centro Hospitalar Lisboa Ocidental, Carnaxide, Portugal
| | - Luís Moreno
- Hospital de Santa Cruz, Centro Hospitalar Lisboa Ocidental, Carnaxide, Portugal
| | - Anaí Durazzo
- Hospital de Santa Cruz, Centro Hospitalar Lisboa Ocidental, Carnaxide, Portugal
| | - Miguel Mendes
- Hospital de Santa Cruz, Centro Hospitalar Lisboa Ocidental, Carnaxide, Portugal
| | - Piergiuseppe Agostoni
- Centro Cardiologico Monzino, IRCCS, Milan, Italy
- Department of Clinical Sciences and Community Health, University of Milan, Italy
| |
Collapse
|
|
9
|
Wernhart S, Papathanasiou M, Jakstaite A, Hoffmann J, Schmack B, Hedderich J, Ruhparwar A, Rassaf T, Luedike P. Exercise oscillatory ventilation in patients with advanced heart failure with and without left ventricular assist device. Artif Organs 2023; 47:168-179. [PMID: 36102469 DOI: 10.1111/aor.14398] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 06/25/2022] [Accepted: 08/26/2022] [Indexed: 01/04/2023]
Abstract
BACKGROUND Exercise oscillatory ventilation (EOV), indicating pathological fluctuations on pulmonary arterial pressure, is associated with mortality in patients with heart failure (HF). Whether left ventricular assist device (LVAD)-induced ventricular unloading can reverse EOV and may prevent short-term rehospitalization has not been investigated. METHODS We performed a retrospective single-center in- and outpatient analysis of patients with (n = 20, LVAD) and without (n = 27, HF) circulatory support and reduced ejection fraction (EF, 22.8 ± 7.9%). The association of cardiopulmonary exercise testing (CPET) variables and 3 months-rehospitalization (3MR) as a primary outcome was analyzed. Furthermore, CPET variables were compared regarding the presence of EOV (+/-). RESULTS Lower VO2peak (11.6 ± 4.9 ml/kg/min vs. 14.4 ± 4.3 ml/kg/min, p = 0.039), lower increase of PETCO2 (CI = 0.049-1.127; p = 0.068), and higher VE/VCO2 (43.8 ± 9.5 vs. 38.3 ± 10.6; p = 0.069) were associated with 3MR. Flattening of O2 pulse (CI = 0.139-2.379; p = 0.487) had no impact on 3MR. EOV was present in 59.5% (n = 28/47) of patients, without a significant difference between LVAD and HF patients (p = 0.959). Patients with HF/EOV+ demonstrated significantly lower VO2peak compared with HF/EOV- (p = 0.039). LVAD/EOV+ displayed significantly lower EF (p = 0.004) and fewer aortic valve opening than LVAD/EOV- (p = 0.027). CONCLUSIONS Lower VO2peak , but not EOV, was associated with 3MR. EOV occurred at a similar rate in LVAD and HF patients, which may illustrate insufficient unloading during exercise in chronic LVAD therapy and may contribute to the limited exercise capacity following LVAD implantation. Simultaneous CPET and right heart catheterization studies are needed to elucidate whether EOV may serve as a non-invasive predictor of insufficient LV unloading necessitating LVAD reprograming.
Collapse
Affiliation(s)
- Simon Wernhart
- Department of Cardiology and Vascular Medicine, West German Heart- and Vascular Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Maria Papathanasiou
- Department of Cardiology and Vascular Medicine, West German Heart- and Vascular Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Aiste Jakstaite
- Department of Cardiology and Vascular Medicine, West German Heart- and Vascular Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Julia Hoffmann
- Department of Cardiology and Vascular Medicine, West German Heart- and Vascular Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Bastian Schmack
- Clinic of Thoracic and Cardiovascular Surgery, West German Heart- and Vascular Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Jürgen Hedderich
- Medistat- Biomedical Statistics, Medistat GmbH, Kronshagen, Germany
| | - Arjang Ruhparwar
- Clinic of Thoracic and Cardiovascular Surgery, West German Heart- and Vascular Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Tienush Rassaf
- Department of Cardiology and Vascular Medicine, West German Heart- and Vascular Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Peter Luedike
- Department of Cardiology and Vascular Medicine, West German Heart- and Vascular Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| |
Collapse
|
|
10
|
A Methodological Perspective on the Function and Assessment of Peripheral Chemoreceptors in Heart Failure: A Review of Data from Clinical Trials. Biomolecules 2022; 12:biom12121758. [PMID: 36551186 PMCID: PMC9775522 DOI: 10.3390/biom12121758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 11/22/2022] [Accepted: 11/24/2022] [Indexed: 11/29/2022] Open
Abstract
Augmented peripheral chemoreceptor sensitivity (PChS) is a common feature of many sympathetically mediated diseases, among others, and it is an important mechanism of the pathophysiology of heart failure (HF). It is related not only to the greater severity of symptoms, especially to dyspnea and lower exercise tolerance but also to a greater prevalence of complications and poor prognosis. The causes, mechanisms, and impact of the enhanced activity of peripheral chemoreceptors (PChR) in the HF population are subject to intense research. Several methodologies have been established and utilized to assess the PChR function. Each of them presents certain advantages and limitations. Furthermore, numerous factors could influence and modulate the response from PChR in studied subjects. Nevertheless, even with the impressive number of studies conducted in this field, there are still some gaps in knowledge that require further research. We performed a review of all clinical trials in HF human patients, in which the function of PChR was evaluated. This review provides an extensive synthesis of studies evaluating PChR function in the HF human population, including methods used, factors potentially influencing the results, and predictors of increased PChS.
Collapse
|
|
11
|
Belli-Marin JFC, Bocchi EA, Ayub-Ferreira S, Junior NC, Guimarães GV. Effects of β-blocker therapy on exercise oscillatory ventilation in reduced ejection fraction heart failure patients: A case series study. Biomed Pharmacother 2022; 152:113106. [PMID: 35665667 DOI: 10.1016/j.biopha.2022.113106] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 05/03/2022] [Accepted: 05/10/2022] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND Exercise oscillatory ventilation (EOV) is an abnormal breathing pattern that occurs in ~20% of patients with heart failure (HF) and is associated with poor prognosis and exercise intolerance. β-blockers (βb) are prescribed for most HF patients; however, their effect on EOV remains unclear. We evaluated the effect of βb on EOV in HF patients with reduced ejection fraction (HFrEF). METHODS Fifteen patients diagnosed with HF, ejection fraction < 45%, aged from 18 to 65 years, were included before starting βb therapy. Patients underwent clinical evaluation, cardiopulmonary exercise testing, echocardiography, laboratory exams (norepinephrine levels, B type natriuretic peptide) at baseline and after βb therapy optimized for six months. Presence of exercise oscillatory breathing was determined by two experienced observers who were blinded to the moment of the test (pre or post). RESULTS Fifteen patients (1 female), aged 49.5 ± 2.5 years, with HFrEF, NYHA I-III enrolled in the study. The etiologies of the HFrEF were idiopathic (n = 8) and hypertensive (n = 7). LVEF increased after βb therapy from 25.9 ± 2.5% to 33 ± 2.6%, P = 0.02; peak VO2 did not significantly change (21.8 ± 1.7 vs 24.7 ± 1.9, P = 0.4); VE/VCO2 slope changed from 32.1 ± 10.6-27.5 ± 9.1, P = 0.03. Before βb initiation, nine patients (60%) had EOV, but only two (13%) did after optimized therapy. McNemar test was used to evaluate the significance of the association between the two moments (P = 0.02). CONCLUSION In patients with HF, medical therapy with βb can reverse EOV. This may explain why these patients experience symptom improvement after βb therapy.
Collapse
Affiliation(s)
| | - Edimar Alcides Bocchi
- Instituto do Coração, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil
| | - Silvia Ayub-Ferreira
- Instituto do Coração, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil
| | - Nelson Carvas Junior
- Instituto do Coração, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil
| | - Guilherme Veiga Guimarães
- Instituto do Coração, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil.
| |
Collapse
|
|
12
|
Toledo C, Ortolani D, Ortiz FC, Marcus NJ, Del Rio R. Potential Role of the Retrotrapezoid Nucleus in Mediating Cardio-Respiratory Dysfunction in Heart Failure With Preserved Ejection Fraction. Front Physiol 2022; 13:863963. [PMID: 35492622 PMCID: PMC9039230 DOI: 10.3389/fphys.2022.863963] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Accepted: 03/29/2022] [Indexed: 01/15/2023] Open
Abstract
A strong association between chemoreflex hypersensitivity, disordered breathing, and elevated sympathetic activity has been shown in experimental and human heart failure (HF). The contribution of chemoreflex hypersensitivity in HF pathophysiology is incompletely understood. There is ample evidence that increased peripheral chemoreflex drive in HF with reduced ejection fraction (HFrEF; EF<40%) leads to pathophysiological changes in autonomic and cardio-respiratory control, but less is known about the neural mechanisms mediating cardio-respiratory disturbances in HF with preserved EF (HFpEF; EF>50%). Importantly, it has been shown that activation of the central chemoreflex worsens autonomic dysfunction in experimental HFpEF, an effect mediated in part by the activation of C1 catecholaminergic neurons neighboring the retrotrapezoid nucleus (RTN), an important region for central chemoreflex control of respiratory and autonomic function. Accordingly, the main purpose of this brief review is to discuss the possible role played by activation of central chemoreflex pathways on autonomic function and its potential role in precipitating disordered breathing in HFpEF. Improving understanding of the contribution of the central chemoreflex to the pathophysiology of HFpEF may help in development of novel interventions intended to improve cardio-respiratory outcomes in HFpEF.
Collapse
Affiliation(s)
- Camilo Toledo
- Laboratory Cardiorespiratory Control, Department of Physiology, Pontificia Universidad Católica de Chile, Santiago, Chile
- Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas, Chile
| | - Domiziana Ortolani
- Laboratory Cardiorespiratory Control, Department of Physiology, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Fernando C. Ortiz
- Mechanisms of Myelin Formation and Repair Laboratory, Facultad de Ciencias de Salud, Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, Santiago, Chile
| | - Noah J. Marcus
- Department of Physiology and Pharmacology, Des Moines University, Des Moines, IA, United States
| | - Rodrigo Del Rio
- Laboratory Cardiorespiratory Control, Department of Physiology, Pontificia Universidad Católica de Chile, Santiago, Chile
- Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas, Chile
- Centro de Envejecimiento y Regeneración (CARE), Pontificia Universidad Católica de Chile, Santiago, Chile
- *Correspondence: Rodrigo Del Rio,
| |
Collapse
|
|
13
|
Piepoli MF, Adamo M, Barison A, Bestetti RB, Biegus J, Böhm M, Butler J, Carapetis J, Ceconi C, Chioncel O, Coats A, Crespo-Leiro MG, de Simone G, Drexel H, Emdin M, Farmakis D, Halle M, Heymans S, Jaarsma T, Jankowska E, Lainscak M, Lam CSP, Løchen ML, Lopatin Y, Maggioni A, Matrone B, Metra M, Noonan K, Pina I, Prescott E, Rosano G, Seferovic PM, Sliwa K, Stewart S, Uijl A, Vaartjes I, Vermeulen R, Verschuren WM, Volterrani M, Von Haehling S, Hoes A. Preventing heart failure: a position paper of the Heart Failure Association in collaboration with the European Association of Preventive Cardiology. Eur J Prev Cardiol 2022; 29:275-300. [PMID: 35083485 DOI: 10.1093/eurjpc/zwab147] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 08/15/2021] [Accepted: 08/18/2021] [Indexed: 02/05/2023]
Abstract
The heart failure epidemic is growing and its prevention, in order to reduce associated hospital readmission rates and its clinical and economic burden, is a key issue in modern cardiovascular medicine. The present consensus document aims to provide practical evidence-based information to support the implementation of effective preventive measures. After reviewing the most common risk factors, an overview of the population attributable risks in different continents is presented, to identify potentially effective opportunities for prevention and to inform preventive strategies. Finally, potential interventions that have been proposed and have been shown to be effective in preventing HF are listed.
Collapse
Affiliation(s)
- Massimo F Piepoli
- Cardiac Unit, Guglielmo da Saliceto Hospital, Piacenza, Italy
- Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy
| | - Marianna Adamo
- Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy
| | - Andrea Barison
- Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy
- Fondazione Toscana Gabriele Monasterio, Pisa, Italy
| | | | - Jan Biegus
- Department of Heart Diseases, Medical University, Wroclaw, Poland
| | - Michael Böhm
- Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Saarland University, Homburg/Saar, Germany
| | - Javed Butler
- Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA
| | - Jonathan Carapetis
- Telethon Kids Institute, University of Western Australia and Perth Children's Hospital, Perth, Australia
| | - Claudio Ceconi
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
| | - Ovidiu Chioncel
- University of Medicine Carol Davila, Bucharest, Romania
- Emergency Institute for Cardiovascular Diseases 'C.C. Iliescu', Bucharest, Romania
| | | | - Maria G Crespo-Leiro
- Complexo Hospitalario Universitario A Coruña (CHUAC): CIBERCV, Universidade da Coruña (UDC), Instituto Ciencias Biomedicas A Coruña (INIBIC), A Coruña, Spain
| | - Giovanni de Simone
- Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
| | - Heinz Drexel
- Department of Medicine, Landeskrankenhaus Bregenz, Bregenz, Austria
- VIVIT, Landeskrankenhaus Feldkirch, Feldkirch, Austria
| | - Michele Emdin
- Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy
- Fondazione Toscana Gabriele Monasterio, Pisa, Italy
| | | | - Martin Halle
- Sport and Health Sciences, Policlinic for Preventive and Rehabilitative Sports Medicine, TUM School of Medicine, Munich, Germany
| | - Stephane Heymans
- Department of Cardiology, Maastricht University, CARIM School for Cardiovascular Diseases, Maastricht, Netherlands
- Centre for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Belgium
| | - Tiny Jaarsma
- Department of Health, Medicine and Caring Sciences, Linkoping University, Linköping, Sweden
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Ewa Jankowska
- Department of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland
| | - Mitja Lainscak
- Division of Cardiology, General Hospital Murska Sobota and Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
- Faculty of Natural Sciences and Mathematics, University of Maribor, Maribor, Slovenia
| | - Carolyn S P Lam
- National Heart Centre Singapore, Duke-National University of Singapore, Singapore, Singapore
| | - Maja-Lisa Løchen
- Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway
| | - Yuri Lopatin
- Volgograd State Medical University, Regional Cardiology Centre, Volgograd, Russian Federation
| | | | | | - Marco Metra
- Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy
| | - Katharine Noonan
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
| | | | - Eva Prescott
- Bispebjerg Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark
| | | | - Petar M Seferovic
- Belgrade University Faculty of Medicine, Serbian Academy of Science and Arts, Belgrade, Serbia
| | - Karen Sliwa
- University of Cape Town, Cape Town, South Africa
| | - Simon Stewart
- Torrens University Australia, Adelaide, South Australia, Australia
| | - Alicia Uijl
- Centre for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Belgium
- Division of Heart & Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
- Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Ilonca Vaartjes
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Roel Vermeulen
- Division of Heart & Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - W M Verschuren
- National Institute for Public Health and the Environment, Bilthoven, the Netherlands
- Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands
| | | | - Stephan Von Haehling
- Department of Cardiology and Pneumology, Heart Center, University of Göttingen Medical Center, Göttingen, Germany
- German Center for Cardiovascular Research (DZHK), partner site Göttingen, Germany
| | - Arno Hoes
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| |
Collapse
|
|
14
|
Periodic Breathing in Cardiopulmonary Exercise Testing: Exercise Oscillatory Ventilation in Heart Failure. Ann Am Thorac Soc 2022; 19:120-126. [PMID: 34971352 DOI: 10.1513/annalsats.202105-559cc] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
|
|
15
|
Piepoli MF, Adamo M, Barison A, Bestetti RB, Biegus J, Böhm M, Butler J, Carapetis J, Ceconi C, Chioncel O, Coats A, Crespo-Leiro MG, de Simone G, Drexel H, Emdin M, Farmakis D, Halle M, Heymans S, Jaarsma T, Jankowska E, Lainscak M, Lam CSP, Løchen ML, Lopatin Y, Maggioni A, Matrone B, Metra M, Noonan K, Pina I, Prescott E, Rosano G, Seferovic PM, Sliwa K, Stewart S, Uijl A, Vaartjes I, Vermeulen R, Monique Verschuren WM, Volterrani M, von Heahling S, Hoes A. Preventing heart failure: a position paper of the Heart Failure Association in collaboration with the European Association of Preventive Cardiology. Eur J Heart Fail 2022; 24:143-168. [PMID: 35083829 DOI: 10.1002/ejhf.2351] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 08/15/2021] [Accepted: 08/18/2021] [Indexed: 12/16/2022] Open
Abstract
The heart failure epidemic is growing and its prevention, in order to reduce associated hospital readmission rates and its clinical and economic burden, is a key issue in modern cardiovascular medicine. The present position paper aims to provide practical evidence-based information to support the implementation of effective preventive measures. After reviewing the most common risk factors, an overview of the population attributable risks in different continents is presented, to identify potentially effective opportunities for prevention and to inform preventive strategies. Finally, potential interventions that have been proposed and have been shown to be effective in preventing heart failure are listed.
Collapse
Affiliation(s)
- Massimo F Piepoli
- Cardiac Unit, Guglielmo da Saliceto Hospital, Piacenza, Italy
- Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy
| | - Marianna Adamo
- Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy
| | - Andrea Barison
- Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy
- Fondazione Toscana Gabriele Monasterio, Pisa, Italy
| | | | - Jan Biegus
- Department of Heart Diseases, Medical University, Wroclaw, Poland
| | - Michael Böhm
- Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Saarland University, Homburg/Saar, Germany
| | - Javed Butler
- Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA
| | - Jonathan Carapetis
- Telethon Kids Institute, University of Western Australia and Perth Children's Hospital, Perth, Australia
| | - Claudio Ceconi
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
| | - Ovidiu Chioncel
- University of Medicine Carol Davila, Bucharest, Romania
- Emergency Institute for Cardiovascular Diseases 'C.C. Iliescu', Bucharest, Romania
| | | | - Maria G Crespo-Leiro
- Complexo Hospitalario Universitario A Coruña (CHUAC): CIBERCV, Universidade da Coruña (UDC), Instituto Ciencias Biomedicas A Coruña (INIBIC), A Coruña, Spain
| | - Giovanni de Simone
- Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
| | - Heinz Drexel
- Department of Medicine, Landeskrankenhaus Bregenz, Bregenz, Austria
- VIVIT, Landeskrankenhaus Feldkirch, Feldkirch, Austria
| | - Michele Emdin
- Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy
- Fondazione Toscana Gabriele Monasterio, Pisa, Italy
| | | | - Martin Halle
- Sport and Health Sciences, Policlinic for Preventive and Rehabilitative Sports Medicine, TUM School of Medicine, Munich, Germany
| | - Stephane Heymans
- Department of Cardiology, Maastricht University, CARIM School for Cardiovascular Diseases, Maastricht, the Netherlands
- Centre for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Belgium
| | - Tiny Jaarsma
- Department of Health, Medicine and Caring Sciences, Linkoping University, Linköping, Sweden
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Ewa Jankowska
- Department of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland
| | - Mitja Lainscak
- Division of Cardiology, General Hospital Murska Sobota and Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
- Faculty of Natural Sciences and Mathematics, University of Maribor, Maribor, Slovenia
| | - Carolyn S P Lam
- National Heart Centre Singapore, Duke-National University of Singapore, Singapore, Singapore
| | - Maja-Lisa Løchen
- Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway
| | - Yuri Lopatin
- Volgograd State Medical University, Regional Cardiology Centre, Volgograd, Russian Federation
| | | | | | - Marco Metra
- Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy
| | - Katharine Noonan
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
| | | | - Eva Prescott
- Bispebjerg Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark
| | | | - Petar M Seferovic
- Belgrade University Faculty of Medicine, Serbian Academy of Science and Arts, Belgrade, Serbia
| | - Karen Sliwa
- University of Cape Town, Cape Town, South Africa
| | - Simon Stewart
- Torrens University Australia, Adelaide, South Australia, Australia
| | - Alicia Uijl
- Centre for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Belgium
- Division of Heart & Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
- Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Ilonca Vaartjes
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Roel Vermeulen
- Division of Heart & Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - W M Monique Verschuren
- National Institute for Public Health and the Environment, Bilthoven, the Netherlands
- Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands
| | | | - Stephan von Heahling
- Department of Cardiology and Pneumology, Heart Center, University of Göttingen Medical Center, Göttingen, Germany
- German Center for Cardiovascular Research (DZHK), partner site Göttingen, Germany
| | - Arno Hoes
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| |
Collapse
|
|
16
|
Díaz-Jara E, Díaz HS, Rios-Gallardo A, Ortolani D, Andrade DC, Toledo C, Pereyra KV, Schwarz K, Ramirez G, Ortiz FC, Andía ME, Del Rio R. Exercise training reduces brainstem oxidative stress and restores normal breathing function in heart failure. Free Radic Biol Med 2021; 172:470-481. [PMID: 34216779 DOI: 10.1016/j.freeradbiomed.2021.06.032] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 06/25/2021] [Accepted: 06/29/2021] [Indexed: 10/21/2022]
Abstract
Enhanced central chemoreflex drive and irregular breathing are both hallmarks in heart failure (HF) and closely related to disease progression. Central chemoreceptor neurons located within the retrotrapezoid nucleus (RTN) are known to play a role in breathing alterations in HF. It has been shown that exercise (EX) effectively reduced reactive oxygen species (ROS) in HF rats. However, the link between EX and ROS, particularly at the RTN, with breathing alterations in HF has not been previously addressed. Accordingly, we aimed to determine: i) ROS levels in the RTN in HF and its association with chemoreflex drive, ii) whether EX improves chemoreflex/breathing function by reducing ROS levels, and iii) determine molecular alterations associated with ROS generation within the RTN of HF rats and study EX effects on these pathways. Adult male Sprague-Dawley rats were allocated into 3 experimental groups: Sham (n = 5), volume overloaded HF (n = 6) and HF (n = 8) rats that underwent EX training for 6 weeks (60 min/day, 25 m/min, 10% inclination). At 8 weeks post-HF induction, breathing patterns and chemoreflex function were analyzed by unrestrained plethysmography. ROS levels and anti/pro-oxidant enzymes gene expression were analyzed in the RTN. Our results showed that HF rats have high ROS levels in the RTN which were closely linked to the enhanced central chemoreflex and breathing disorders. Also, HF rats displayed decreased expression of antioxidant genes in the RTN compared with control rats. EX training increases antioxidant defense in the RTN, reduces ROS formation and restores normal central chemoreflex drive and breathing regularity in HF rats. This study provides evidence for a role of ROS in central chemoreception in the setting of HF and support the use of EX to reduce ROS in the brainstem of HF animals and reveal its potential as an effective mean to normalize chemoreflex and breathing function in HF.
Collapse
Affiliation(s)
- Esteban Díaz-Jara
- Laboratory of Cardiorespiratory Control, Pontificia Universidad Católica de Chile, 8331150, Santiago, Chile.
| | - Hugo S Díaz
- Laboratory of Cardiorespiratory Control, Pontificia Universidad Católica de Chile, 8331150, Santiago, Chile.
| | - Angélica Rios-Gallardo
- Laboratory of Cardiorespiratory Control, Pontificia Universidad Católica de Chile, 8331150, Santiago, Chile; Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, 621-0427, Punta Arenas, Chile.
| | - Domiziana Ortolani
- Laboratory of Cardiorespiratory Control, Pontificia Universidad Católica de Chile, 8331150, Santiago, Chile.
| | - David C Andrade
- Laboratory of Cardiorespiratory Control, Pontificia Universidad Católica de Chile, 8331150, Santiago, Chile; Centro de Fisiología y Medicina de Altura, Facultad de Ciencias de la Salud, Universidad de Antofagasta, 1270300, Antofagasta, Chile.
| | - Camilo Toledo
- Laboratory of Cardiorespiratory Control, Pontificia Universidad Católica de Chile, 8331150, Santiago, Chile; Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, 621-0427, Punta Arenas, Chile.
| | - Katherin V Pereyra
- Laboratory of Cardiorespiratory Control, Pontificia Universidad Católica de Chile, 8331150, Santiago, Chile.
| | - Karla Schwarz
- Laboratory of Cardiorespiratory Control, Pontificia Universidad Católica de Chile, 8331150, Santiago, Chile.
| | - Gigliola Ramirez
- Laboratory of Cardiorespiratory Control, Pontificia Universidad Católica de Chile, 8331150, Santiago, Chile.
| | - Fernando C Ortiz
- Centro de Investigación Biomédica, Universidad Autónoma de Chile, Santiago, Chile.
| | - Marcelo E Andía
- Radiology Department & ANID - Millennium Nucleus for Cardiovascular Magnetic Resonance, 8331150, Pontificia Universidad Católica de Chile, Santiago, Chile.
| | - Rodrigo Del Rio
- Laboratory of Cardiorespiratory Control, Pontificia Universidad Católica de Chile, 8331150, Santiago, Chile; Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, 621-0427, Punta Arenas, Chile; Centro de Envejecimiento y Regeneración (CARE), Pontificia Universidad Católica de Chile, 8331150, Santiago, Chile.
| |
Collapse
|
|
17
|
Exercising in Hypoxia and Other Stimuli: Heart Rate Variability and Ventilatory Oscillations. Life (Basel) 2021; 11:life11070625. [PMID: 34203350 PMCID: PMC8306822 DOI: 10.3390/life11070625] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 06/22/2021] [Accepted: 06/27/2021] [Indexed: 12/24/2022] Open
Abstract
Periodic breathing is a respiratory phenomenon frequently observed in patients with heart failure and in normal subjects sleeping at high altitude. However, until recently, periodic breathing has not been studied in wakefulness and during exercise. This review relates the latest findings describing this ventilatory disorder when a healthy subject is submitted to simultaneous physiological (exercise) and environmental (hypoxia, hyperoxia, hypercapnia) or pharmacological (acetazolamide) stimuli. Preliminary studies have unveiled fundamental physiological mechanisms related to the genesis of periodic breathing characterized by a shorter period than those observed in patients (11~12 vs. 30~60 s). A mathematical model of the respiratory system functioning under the aforementioned stressors corroborated these data and pointed out other parameters, such as dead space, later confirmed in further research protocols. Finally, a cardiorespiratory interdependence between ventilatory oscillations and heart rate variability in the low frequency band may partly explain the origin of the augmented sympathetic activation at exercise in hypoxia. These nonlinear instabilities highlight the intrinsic "homeodynamic" system that allows any living organism to adapt, to a certain extent, to permanent environmental and internal perturbations.
Collapse
|
|
18
|
Sakellaropoulos SG, Baggish AL, Fifer MA, Lewis GD. Exercise Oscillatory Ventilation in Hypertrophic Cardiomyopathy. Curr Probl Cardiol 2021; 47:100911. [PMID: 34210521 DOI: 10.1016/j.cpcardiol.2021.100911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Accepted: 05/20/2021] [Indexed: 11/03/2022]
Abstract
To assess the prevalence and clinical correlates of exercise oscillatory ventilation (EOV) in patients with hypertrophic cardiomyopathy (HCM). Retrospective single-center study. Thirty-six consecutive HCM patients who underwent cardiopulmonary exercise testing. Two patients (5.6%) had EOV. Both patients with peak oxygen consumption (VO2) less than or equal to 9.1 ml/kg/min had EOV. Left atrial size was greater in patients with EOV. Of the 2 patients in the study population with an abnormal blood pressure response to exercise, 1 had EOV. Both patients with New York Heart Association Class 3 heart failure had EOV. This is the first report of EOV in HCM. EOV is uncommon in patients with HCM. EOV appears to be a marker of disease severity as evidenced by overt heart failure, left atrial enlargement, and low peak VO2.
Collapse
Affiliation(s)
- Stefanos G Sakellaropoulos
- Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
| | - Aaron L Baggish
- Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA
| | - Michael A Fifer
- Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA
| | - Gregory D Lewis
- Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA
| |
Collapse
|
|
19
|
Orr JE, Ayappa I, Eckert DJ, Feldman JL, Jackson CL, Javaheri S, Khayat RN, Martin JL, Mehra R, Naughton MT, Randerath WJ, Sands SA, Somers VK, Badr MS. Research Priorities for Patients with Heart Failure and Central Sleep Apnea. An Official American Thoracic Society Research Statement. Am J Respir Crit Care Med 2021; 203:e11-e24. [PMID: 33719931 PMCID: PMC7958519 DOI: 10.1164/rccm.202101-0190st] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Background: Central sleep apnea (CSA) is common among patients with heart failure and has been strongly linked to adverse outcomes. However, progress toward improving outcomes for such patients has been limited. The purpose of this official statement from the American Thoracic Society is to identify key areas to prioritize for future research regarding CSA in heart failure. Methods: An international multidisciplinary group with expertise in sleep medicine, pulmonary medicine, heart failure, clinical research, and health outcomes was convened. The group met at the American Thoracic Society 2019 International Conference to determine research priority areas. A statement summarizing the findings of the group was subsequently authored using input from all members. Results: The workgroup identified 11 specific research priorities in several key areas: 1) control of breathing and pathophysiology leading to CSA, 2) variability across individuals and over time, 3) techniques to examine CSA pathogenesis and outcomes, 4) impact of device and pharmacological treatment, and 5) implementing CSA treatment for all individuals Conclusions: Advancing care for patients with CSA in the context of heart failure will require progress in the arenas of translational (basic through clinical), epidemiological, and patient-centered outcome research. Given the increasing prevalence of heart failure and its associated substantial burden to individuals, society, and the healthcare system, targeted research to improve knowledge of CSA pathogenesis and treatment is a priority.
Collapse
|
|
20
|
Potratz M, Fox H, Rudolph V, Faber L, Dumitrescu D, Bitter T. Respiratory dyssynchrony is a predictor of prognosis in patients with hypertrophic non-obstructive cardiomyopathy. Int J Cardiol 2021; 332:105-112. [PMID: 33667581 DOI: 10.1016/j.ijcard.2021.02.077] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Accepted: 02/26/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Respiratory dyssynchrony (RD) is a phenomenon that may be reflected by reduced breathing efficiency (CO2 output relative to minute ventilation, V̇E/V̇CO2 slope) or by Exercise oscillatory ventilation (EOV). Low breathing efficiency and EOV indicate a worse prognosis in chronic heart failure patients with reduced ejection fraction (HFrEF). However, only little is known about their role in other forms of structural myocardial diseases. In this study, we assessed the prognostic impact of RD in hypertrophic non-obstructive cardiomyopathy (HNCM) as a subgroup of patients with heart failure and preserved ejection fraction (HFpEF). METHODS AND RESULTS We selected n = 132 HNCM patients (pts) who underwent cardiopulmonary exercise testing (CPET) during baseline assessment. The average follow-up was 4.3 ± 3.6 years. The primary endpoint was a composite of death, heart transplantation (HTX), and implantation of a ventricular assist device (VAD). Respiratory dyssynchrony, as measured by EOV, was recorded in 18 pts. (14%), and as measured by a V̇E/V̇CO2 relationship of higher than 34 in 34 pts. (26%). In total, 22 (16.7%) pts. met the endpoint. Multivariate COX regression Analysis were made for EOV, V̇E/V̇CO2 and the combination of EOV andV̇E/V̇CO2. All parameters correlated significantly with the endpoint: EOV (hazard ratio [HR]: 3.7; p = 0.006), V̇E/V̇CO2 > 34 (HR: 5.6; p = 0.001) and EOV andV̇E/V̇CO2: (HR: 6.1; p ≤ 0.001). CONCLUSION This is the first study to demonstrate the prognostic impact of RD on pts. with HNCM, and to investigate EOV as a novel factor to aid risk stratification in HNCM.
Collapse
Affiliation(s)
- Max Potratz
- Clinic for General and Interventional Cardiology/Angiology, Herz-und Diabeteszentrum NRW, Ruhr-Universität Bochum, Bad Oeynhausen, Germany.
| | - Henrik Fox
- Clinic for General and Interventional Cardiology/Angiology, Herz-und Diabeteszentrum NRW, Ruhr-Universität Bochum, Bad Oeynhausen, Germany
| | - Volker Rudolph
- Clinic for General and Interventional Cardiology/Angiology, Herz-und Diabeteszentrum NRW, Ruhr-Universität Bochum, Bad Oeynhausen, Germany
| | - Lothar Faber
- Clinic for General and Interventional Cardiology/Angiology, Herz-und Diabeteszentrum NRW, Ruhr-Universität Bochum, Bad Oeynhausen, Germany
| | - Daniel Dumitrescu
- Clinic for General and Interventional Cardiology/Angiology, Herz-und Diabeteszentrum NRW, Ruhr-Universität Bochum, Bad Oeynhausen, Germany
| | - Thomas Bitter
- Clinic for General and Interventional Cardiology/Angiology, Herz-und Diabeteszentrum NRW, Ruhr-Universität Bochum, Bad Oeynhausen, Germany
| |
Collapse
|
|
21
|
Keir DA, Duffin J, Floras JS. Measuring Peripheral Chemoreflex Hypersensitivity in Heart Failure. Front Physiol 2020; 11:595486. [PMID: 33447244 PMCID: PMC7802759 DOI: 10.3389/fphys.2020.595486] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2020] [Accepted: 11/30/2020] [Indexed: 01/08/2023] Open
Abstract
Heart failure with reduced ejection fraction (HFrEF) induces chronic sympathetic activation. This disturbance is a consequence of both compensatory reflex disinhibition in response to lower cardiac output and patient-specific activation of one or more excitatory stimuli. The result is the net adrenergic output that exceeds homeostatic need, which compromises cardiac, renal, and vascular function and foreshortens lifespan. One such sympatho-excitatory mechanism, evident in ~40-45% of those with HFrEF, is the augmentation of carotid (peripheral) chemoreflex ventilatory and sympathetic responsiveness to reductions in arterial oxygen tension and acidosis. Recognition of the contribution of increased chemoreflex gain to the pathophysiology of HFrEF and to patients' prognosis has focused attention on targeting the carotid body to attenuate sympathetic drive, alleviate heart failure symptoms, and prolong life. The current challenge is to identify those patients most likely to benefit from such interventions. Two assumptions underlying contemporary test protocols are that the ventilatory response to acute hypoxic exposure quantifies accurately peripheral chemoreflex sensitivity and that the unmeasured sympathetic response mirrors the determined ventilatory response. This Perspective questions both assumptions, illustrates the limitations of conventional transient hypoxic tests for assessing peripheral chemoreflex sensitivity and demonstrates how a modified rebreathing test capable of comprehensively quantifying both the ventilatory and sympathoneural efferent responses to peripheral chemoreflex perturbation, including their sensitivities and recruitment thresholds, can better identify individuals most likely to benefit from carotid body intervention.
Collapse
Affiliation(s)
- Daniel A. Keir
- University Health Network and Mount Sinai Hospital Division of Cardiology and Department of Medicine, University of Toronto, Toronto General Research Institute, Toronto, ON, Canada
- School of Kinesiology, The University of Western Ontario, London, ON, Canada
| | - James Duffin
- Department of Anesthesia and Pain Management, University of Toronto, Toronto, ON, Canada
- Department of Physiology, University of Toronto, Toronto, ON, Canada
- Thornhill Research Inc., Toronto, ON, Canada
| | - John S. Floras
- University Health Network and Mount Sinai Hospital Division of Cardiology and Department of Medicine, University of Toronto, Toronto General Research Institute, Toronto, ON, Canada
| |
Collapse
|
|
22
|
Giannoni A, Gentile F, Sciarrone P, Borrelli C, Pasero G, Mirizzi G, Vergaro G, Poletti R, Piepoli MF, Emdin M, Passino C. Upright Cheyne-Stokes Respiration in Patients With Heart Failure. J Am Coll Cardiol 2020; 75:2934-2946. [DOI: 10.1016/j.jacc.2020.04.033] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Revised: 04/10/2020] [Accepted: 04/13/2020] [Indexed: 12/28/2022]
|
|
23
|
Mitigation of Exercise Oscillatory Ventilation Score by Cardiac Resynchronization Therapy. J Card Fail 2020; 26:832-840. [PMID: 32205188 DOI: 10.1016/j.cardfail.2020.03.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Revised: 03/04/2020] [Accepted: 03/16/2020] [Indexed: 11/23/2022]
Abstract
BACKGROUND Exercise oscillatory ventilation (EOV) is a consequence of ventilatory control system instability and is commonly observed in patients with advanced heart failure (HF); it is associated with adverse prognosis. The goal of this study was to evaluate the effects of cardiac resynchronization therapy (CRT) on oscillatory ventilation as quantified by a proposed EOV score. METHODS AND RESULTS Consecutive patients with HF (N = 35) who underwent clinically indicated CRT, cardiopulmonary exercise testing and carbon dioxide (CO2) chemosensitivity by rebreathe before and 4-6 months after CRT were included in this post hoc analysis. With CRT, EOV scores improved in 22 patients (63%). In these patients, left ventricular ejection fraction, left atrial volume, brain natriuretic peptide concentration, and CO2 chemosensitivity significantly improved after CRT (P < 0.05). Furthermore, minute ventilation per unit CO2 production significantly decreased, and end-tidal CO2 increased at rest and at peak exercise post-CRT. Multiple regression analysis showed only the change of CO2 chemosensitivity to be significantly associated with the improvement of the EOV score (b = 0.64; F = 11.3; P = 0.004). In the group without EOV score improvement (n = 13), though left ventricular ejection fraction significantly increased with CRT (P = 0.015), no significant changes in ventilation or gas exchange were observed. CONCLUSION The EOV score was mitigated by CRT and was associated with decreased CO2 chemosensitivity.
Collapse
|
|
24
|
Abstract
The heart and lungs are intimately linked. Hence, impaired function of one organ may lead to changes in the other. Accordingly, heart failure is associated with airway obstruction, loss of lung volume, impaired gas exchange, and abnormal ventilatory control. Cardiopulmonary exercise testing is an excellent tool for evaluation of gas exchange and ventilatory control. Indeed, many parameters routinely measured during cardiopulmonary exercise testing, including the level of minute ventilation per unit of carbon dioxide production and the presence of exercise oscillatory ventilation, have been found to be strongly associated with prognosis in patients with heart failure.
Collapse
Affiliation(s)
- Ivan Cundrle
- Department of Anesthesiology and Intensive Care, St. Anne's University Hospital, Pekarska 53, Brno 65691, Czech Republic; Faculty of Medicine, Masaryk University, Brno, Czech Republic; International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic
| | - Lyle J Olson
- Department of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - Bruce D Johnson
- Department of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
| |
Collapse
|
|
25
|
Kinoshita H, Sairaku A, Morishima N, Dohi Y, Sada Y, Higashi A, Yamabe S, Kihara Y. Prognostic significance of oscillatory ventilation at rest in patients with advanced heart failure undergoing cardiopulmonary exercise testing. Int J Cardiol 2020; 301:142-146. [DOI: 10.1016/j.ijcard.2019.11.098] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Revised: 10/24/2019] [Accepted: 11/11/2019] [Indexed: 01/04/2023]
|
|
26
|
Kahn D, Baele P, Pasquet A, Liistro G. Cheyne-Stokes respiration and cardiovascular oscillations ending abruptly when deploying transfemoral aortic valve. J Appl Physiol (1985) 2020; 128:345-349. [PMID: 31873067 DOI: 10.1152/japplphysiol.00193.2019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
A 86-yr-old man was referred for transfemoral aortic valve implantation. Transthoracic echocardiography revealed a severe stenosis (mean gradient: 58 mmHg, aortic valve area: 0.4 cm2), and after multidisciplinary discussion, the risk of surgery was judged too high (logistic Euroscore: 51%), and the patient was proposed for a transfemoral aortic valve implantation (TAVI). On arrival in the operating room, the patient, fully conscious, was noted to have Cheyne-Stokes breathing (CSB), which persisted after 40% oxygen administration. TAVI procedure was successful, and the CSB pattern was interrupted within 8 s. To the best of our knowledge, this report is the first to show an acute disappearance of CSB, occurring only seconds after TAVI and restoration of a normal hemodynamic situation. To explain such rapid changes in breathing pattern, we hypothesize a role played by the acute release of pulmonary hypertension and pulmonary volume overload.NEW & NOTEWORTHY Acute disappearance of Cheyne-Stokes breathing after transfemoral aortic valve implantation suggests a reflex pathway originating from the fall in pulmonary vessels congestion.
Collapse
Affiliation(s)
- David Kahn
- Department of Anaesthesiology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Philippe Baele
- Department of Anaesthesiology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Agnès Pasquet
- Division of Cardiology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Giuseppe Liistro
- Pôle de Pneumologie, ORL et Dermatologie, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium.,Service de Pneumologie, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| |
Collapse
|
|
27
|
Nakade T, Adachi H, Murata M, Naito S. Relationship Between Respiratory Compensation Point and Anaerobic Threshold in Patients With Heart Failure With Reduced Ejection Fraction. Circ J 2019; 84:76-82. [PMID: 31776308 DOI: 10.1253/circj.cj-19-0561] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND Cardiopulmonary exercise testing (CPX) is used in the prognostic evaluation of patients with heart failure with reduced ejection fraction (HFrEF). In these patients, the ventilation feedback system is dysfunctional, and overactive peripheral chemoreceptors may be responsible for the early appearance of the respiratory compensation point (RCP) after the anaerobic threshold (AT). The mechanism of RCP appearance remains unknown and very few studies have reported the relationship between RCP and heart failure. We hypothesized that the duration between the RCP and AT (RCP-AT time) can predict the severity of cardiac disorders and prognosis in patients with HFrEF. METHODS AND RESULTS We enrolled 143 patients with HFrEF who underwent symptom-limited maximal CPX between 2012 and 2016. During a median follow-up of 1.4 years, cardiovascular death occurred in 45 participants (31%). The patients who died had a significantly shorter RCP-AT time and lower hemoglobin (Hb) levels than those who survived (P<0.001 and P=0.01, respectively). Cox regression analyses revealed RCP-AT time and Hb level to be independent predictors of cardiovascular death in patients with HFrEF (P<0.001 and P=0.018, respectively). CONCLUSIONS RCP-AT time can better predict prognosis in patients with HFrEF than the magnitude of increase in oxygen consumption within the isocapnic buffering domain (∆V̇O2AT-RCP). It may be useful as a new prognostic indicator in these patients.
Collapse
Affiliation(s)
- Taisuke Nakade
- Department of Cardiology, Gunma Prefectural Cardiovascular Center
| | - Hitoshi Adachi
- Department of Cardiology, Gunma Prefectural Cardiovascular Center
| | - Makoto Murata
- Department of Cardiology, Gunma Prefectural Cardiovascular Center
| | - Shigeto Naito
- Department of Cardiology, Gunma Prefectural Cardiovascular Center
| |
Collapse
|
|
28
|
Nakade T, Adachi H, Murata M, Oshima S. Relationship Between Exercise Oscillatory Ventilation Loop and Prognosis of Heart Failure. Circ J 2019; 83:1718-1725. [PMID: 31257356 DOI: 10.1253/circj.cj-18-1047] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2024]
Abstract
BACKGROUND The cardiopulmonary exercise test (CPX) is a tool for evaluating disease severity and limitations in activities of daily living in patients with cardiac disorders. However, few studies have evaluated the association between exercise oscillatory ventilation (EOV) severity and prognosis in heart failure (HF) patients with EOV. EOV severity can be evaluated by detecting endtidal CO2pressure (PETCO2, an indicator of the arterial partial pressure of CO2(PaCO2)) and minute ventilation, which is a reflection of the respiratory response to elevated CO2. We hypothesized that the magnitude of EOV severity can predict the severity and prognosis of cardiac disorders and aimed to validate this hypothesis. METHODS AND RESULTS In total, 2,043 patients who underwent symptom-limited maximal CPX between 2010 and 2016 were evaluated. We enrolled 70 patients who had HF with reduced ejection fraction (HFrEF) and EOV. The endpoint was cardiovascular death. During a median follow-up of 4.3 years, 34 participants died (48%). Those who died showed significantly larger EOV loop size and lower hemoglobin (Hb) levels than those who survived (17.3±7.0 cm2vs. 12.8±6.1 cm2, P<0.001; 12.2±1.2 g/dL vs. 13.2±2.9 g/dL, P=0.004). Cox regression analyses revealed Hb levels and EOV loop size as independent predictors of cardiovascular death in HFrEF patients with EOV. CONCLUSIONS EOV loop size was associated with cardiovascular death of HFrEF patients with EOV.
Collapse
Affiliation(s)
- Taisuke Nakade
- Department of Cardiology, Gunma Prefectural Cardiovascular Center
| | - Hitoshi Adachi
- Department of Cardiology, Gunma Prefectural Cardiovascular Center
| | - Makoto Murata
- Department of Cardiology, Gunma Prefectural Cardiovascular Center
| | - Shigeru Oshima
- Department of Cardiology, Gunma Prefectural Cardiovascular Center
| |
Collapse
|
|
29
|
Giannoni A, Gentile F, Navari A, Borrelli C, Mirizzi G, Catapano G, Vergaro G, Grotti F, Betta M, Piepoli MF, Francis DP, Passino C, Emdin M. Contribution of the Lung to the Genesis of Cheyne-Stokes Respiration in Heart Failure: Plant Gain Beyond Chemoreflex Gain and Circulation Time. J Am Heart Assoc 2019; 8:e012419. [PMID: 31237174 PMCID: PMC6662365 DOI: 10.1161/jaha.119.012419] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Accepted: 05/22/2019] [Indexed: 01/26/2023]
Abstract
Background The contribution of the lung or the plant gain ( PG ; ie, change in blood gases per unit change in ventilation) to Cheyne-Stokes respiration ( CSR ) in heart failure has only been hypothesized by mathematical models, but never been directly evaluated. Methods and Results Twenty patients with systolic heart failure (age, 72.4±6.4 years; left ventricular ejection fraction, 31.5±5.8%), 10 with relevant CSR (24-hour apnea-hypopnea index [ AHI ] ≥10 events/h) and 10 without ( AHI <10 events/h) at 24-hour cardiorespiratory monitoring underwent evaluation of chemoreflex gain (CG) to hypoxia ([Formula: see text]) and hypercapnia ([Formula: see text]) by rebreathing technique, lung-to-finger circulation time, and PG assessment through a visual system. PG test was feasible and reproducible (intraclass correlation coefficient, 0.98; 95% CI , 0.91-0.99); the best-fitting curve to express the PG was a hyperbola ( R2≥0.98). Patients with CSR showed increased PG , [Formula: see text] (but not [Formula: see text]), and lung-to-finger circulation time, compared with patients without CSR (all P<0.05). PG was the only predictor of the daytime AHI ( R=0.56, P=0.01) and together with the [Formula: see text] also predicted the nighttime AHI ( R=0.81, P=0.0003) and the 24-hour AHI ( R=0.71, P=0.001). Lung-to-finger circulation time was the only predictor of CSR cycle length ( R=0.82, P=0.00006). Conclusions PG is a powerful contributor of CSR and should be evaluated together with the CG and circulation time to individualize treatments aimed at stabilizing breathing in heart failure.
Collapse
Affiliation(s)
- Alberto Giannoni
- Fondazione Toscana G. MonasterioPisaItaly
- Institute of Life SciencesScuola Superiore Sant'AnnaPisaItaly
| | | | | | | | | | | | - Giuseppe Vergaro
- Fondazione Toscana G. MonasterioPisaItaly
- Institute of Life SciencesScuola Superiore Sant'AnnaPisaItaly
| | | | | | | | - Darrel P. Francis
- International Center for Circulatory HealthNational Heart and Lung InstituteImperial College LondonLondonUnited Kingdom
| | - Claudio Passino
- Fondazione Toscana G. MonasterioPisaItaly
- Institute of Life SciencesScuola Superiore Sant'AnnaPisaItaly
| | - Michele Emdin
- Fondazione Toscana G. MonasterioPisaItaly
- Institute of Life SciencesScuola Superiore Sant'AnnaPisaItaly
| |
Collapse
|
|
30
|
Abstract
Periodic breathing during incremental cardiopulmonary exercise testing is a regularly recurring waxing and waning of tidal volume due to oscillations in central respiratory drive. Periodic breathing is a sign of respiratory control system instability, which may occur at rest or during exercise. The possible mechanisms responsible for exertional periodic breathing might be related to any instability of the ventilatory regulation caused by: (1) increased circulatory delay (i.e., circulation time from the lung to the brain and chemoreceptors due to reduced cardiac index leading to delay in information transfer), (2) increase in controller gain (i.e., increased central and peripheral chemoreceptor sensitivity to arterial partial pressure of oxygen and of carbon dioxide), or (3) reduction in system damping (i.e., baroreflex impairment). Periodic breathing during exercise is observed in several cardiovascular disease populations, but it is a particularly frequent phenomenon in heart failure due to systolic dysfunction. The detection of exertional periodic breathing is linked to outcome and heralds worse prognosis in heart failure, independently of the criteria adopted for its definition. In small heart failure cohorts, exertional periodic breathing has been abolished with several dedicated interventions, but results have not yet been confirmed. Accordingly, further studies are needed to define the role of visceral feedbacks in determining periodic breathing during exercise as well as to look for specific tools for preventing/treating its occurrence in heart failure.
Collapse
|
|
31
|
Jorgenson CC, Chase SC, Olson LJ, Johnson BD. Assessment of Thoracic Blood Volume by Computerized Tomography in Patients With Heart Failure and Periodic Breathing. J Card Fail 2018; 24:479-483. [PMID: 29678727 DOI: 10.1016/j.cardfail.2018.04.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2017] [Revised: 04/10/2018] [Accepted: 04/10/2018] [Indexed: 10/17/2022]
Abstract
BACKGROUND Periodic breathing (PB) is often observed in patients with HF at rest, with sleep and during exercise. However, mechanisms underlying abnormal ventilatory control are not entirely established. METHODS Eleven subjects with HF (10 males, age = 69 ± 12 y) and 12 age-matched control subjects (8 males, age = 65 ± 9 y) participated in the study. PB was defined as a peak in the 0.003-0.04 Hz frequency range of the flow signal during 6 minutes of awake resting breathing. Thoracic blood volumes (Vt, thorax; Vh, heart; Vp, pulmonary), mean transit times (MTTs), and extravascular lung water (EVLW) were quantified using computerized tomography. RESULTS PB was observed in 7 subjects with HF and was associated with worse functional status. The HF PB-present group had thoracic blood volumes nearly double those of control and HF PB-absent subjects (volumes reported as mL/m2 body surface area, P values vs control: control = 813 ± 246, HF PB-absent = 822 ± 161 P = .981, HF PB-present = 1579 ± 548 P = .002). PB was associated with longer pulmonary MTT (control = 6.7 ± 1.2 s, HF PB-absent = 6.0 ± 0.8 s, HF PB-present = 8.4 ± 1.6 s; P = .033, HF PB-present vs HF PB-absent). EVLW was not elevated in the PB group. CONCLUSIONS Subjects with HF and PB at rest have greater centralization of blood volume.
Collapse
Affiliation(s)
| | - Steven C Chase
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
| | - Lyle J Olson
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
| | - Bruce D Johnson
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota.
| |
Collapse
|
|
32
|
Ayas NT, Laratta CR, Coleman JM, Doufas AG, Eikermann M, Gay PC, Gottlieb DJ, Gurubhagavatula I, Hillman DR, Kaw R, Malhotra A, Mokhlesi B, Morgenthaler TI, Parthasarathy S, Ramachandran SK, Strohl KP, Strollo PJ, Twery MJ, Zee PC, Chung FF. Knowledge Gaps in the Perioperative Management of Adults with Obstructive Sleep Apnea and Obesity Hypoventilation Syndrome. An Official American Thoracic Society Workshop Report. Ann Am Thorac Soc 2018; 15:117-126. [PMID: 29388810 PMCID: PMC6850745 DOI: 10.1513/annalsats.201711-888ws] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
The purpose of this workshop was to identify knowledge gaps in the perioperative management of obstructive sleep apnea (OSA) and obesity hypoventilation syndrome (OHS). A single-day meeting was held at the American Thoracic Society Conference in May, 2016, with representation from many specialties, including anesthesiology, perioperative medicine, sleep, and respiratory medicine. Further research is urgently needed as we look to improve health outcomes for these patients and reduce health care costs. There is currently insufficient evidence to guide screening and optimization of OSA and OHS in the perioperative setting to achieve these objectives. Patients who are at greatest risk of respiratory or cardiac complications related to OSA and OHS are not well defined, and the effectiveness of monitoring and other interventions remains to be determined. Centers involved in sleep research need to develop collaborative networks to allow multicenter studies to address the knowledge gaps identified below.
Collapse
|
|
33
|
Abstract
The cardiopulmonary exercise test (CPX) is an essential examination for detecting pathophysiological derangement and determining treatment policy because it clarifies not only the changes of hemodynamics but also abnormality in the whole body during exercise where heart disease patients often feel symptoms.To utilize CPX effectively, we must understand each parameter, such as peak oxygen uptake (peak VO2), peak VO2/HR, and VE/VCO2. In addition, comparison of each parameter, for example, peak VO2 and VE/VCO2, and peak VO2 and peak VO2/HR, is useful to detect the pathophysiological abnormalities.In this article, I will describe how CPX should be used in clinical settings.
Collapse
Affiliation(s)
- Hitoshi Adachi
- Department of Cardiology, Gunma Prefectural Cardiovascular Center
| |
Collapse
|
|
34
|
Kumagai N, Dohi K, Fujimoto N, Tanimura M, Sato Y, Miyahara S, Nakamori S, Fujii E, Yamada N, Ito M. A novel method for the quantitative evaluation of diurnal respiratory instability in patients with heart failure: A pilot study. J Cardiol 2017; 71:159-167. [PMID: 28958750 DOI: 10.1016/j.jjcc.2017.08.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2016] [Revised: 07/19/2017] [Accepted: 08/09/2017] [Indexed: 02/01/2023]
Abstract
BACKGROUND There is no established method to quantitatively measure the presence and the severity of respiratory instability (RI). The purpose of this pilot study was to propose a novel index of diurnal RI as a surrogate measure of clinical severity of heart failure (HF). METHODS AND RESULTS We prospectively enrolled 60 patients with symptomatic HF [70±14 years, 75% male, and New York Heart Association (NYHA) functional classes II-IV] who underwent right heart catheterization (RHC), and recorded diurnal respiration using a nasal pressure sensor during bed rest while awake within 2 days before or after RHC. Non-uniformity of the breath-by-breath respiratory slopes during 15min calculated as the ratio of peak expiratory amplitude to corresponding peak-to-peak interval was assessed by histogram-based frequency distribution measurement, and was defined as the "RI-index". The RI-index was significantly different among NYHA functional classes and was highest in NYHA class IV. The presence of atrial fibrillation (β coefficient: 0.300, p=0.01) and stroke volume index (β coefficient: -0.462, p<0.01) were independently associated with RI index among hemodynamic parameters. Furthermore, the high RI index above the median value was the independent predictor of the composite outcome of death from any cause, a life-threatening arrhythmia, and an unplanned hospitalization for worsening HF. CONCLUSIONS The RI index stratified functional severity of HF well, and was a significant independent predictor of poor outcomes.
Collapse
Affiliation(s)
- Naoto Kumagai
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Japan
| | - Kaoru Dohi
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Japan.
| | - Naoki Fujimoto
- Department of Molecular and Laboratory Medicine, Mie University Graduate School of Medicine, Tsu, Japan
| | - Muneyoshi Tanimura
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Japan
| | - Yuichi Sato
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Japan
| | - So Miyahara
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Japan
| | - Shiro Nakamori
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Japan
| | - Eitaro Fujii
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Japan
| | - Norikazu Yamada
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Japan
| | - Masaaki Ito
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Japan
| |
Collapse
|
|
35
|
Sands SA, Mebrate Y, Edwards BA, Nemati S, Manisty CH, Desai AS, Wellman A, Willson K, Francis DP, Butler JP, Malhotra A. Resonance as the Mechanism of Daytime Periodic Breathing in Patients with Heart Failure. Am J Respir Crit Care Med 2017; 195:237-246. [PMID: 27559818 DOI: 10.1164/rccm.201604-0761oc] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
RATIONALE In patients with chronic heart failure, daytime oscillatory breathing at rest is associated with a high risk of mortality. Experimental evidence, including exaggerated ventilatory responses to CO2 and prolonged circulation time, implicates the ventilatory control system and suggests feedback instability (loop gain > 1) is responsible. However, daytime oscillatory patterns often appear remarkably irregular versus classic instability (Cheyne-Stokes respiration), suggesting our mechanistic understanding is limited. OBJECTIVES We propose that daytime ventilatory oscillations generally result from a chemoreflex resonance, in which spontaneous biological variations in ventilatory drive repeatedly induce temporary and irregular ringing effects. Importantly, the ease with which spontaneous biological variations induce irregular oscillations (resonance "strength") rises profoundly as loop gain rises toward 1. We tested this hypothesis through a comparison of mathematical predictions against actual measurements in patients with heart failure and healthy control subjects. METHODS In 25 patients with chronic heart failure and 25 control subjects, we examined spontaneous oscillations in ventilation and separately quantified loop gain using dynamic inspired CO2 stimulation. MEASUREMENTS AND MAIN RESULTS Resonance was detected in 24 of 25 patients with heart failure and 18 of 25 control subjects. With increased loop gain-consequent to increased chemosensitivity and delay-the strength of spontaneous oscillations increased precipitously as predicted (r = 0.88), yielding larger (r = 0.78) and more regular (interpeak interval SD, r = -0.68) oscillations (P < 0.001 for all, both groups combined). CONCLUSIONS Our study elucidates the mechanism underlying daytime ventilatory oscillations in heart failure and provides a means to measure and interpret these oscillations to reveal the underlying chemoreflex hypersensitivity and reduced stability that foretells mortality in this population.
Collapse
Affiliation(s)
- Scott A Sands
- 1 Division of Sleep and Circadian Disorders and.,2 Department of Allergy, Immunology and Respiratory Medicine and Central Clinical School, The Alfred and Monash University, Melbourne, Victoria, Australia
| | - Yoseph Mebrate
- 3 International Center for Circulatory Health, National Heart and Lung Institute, Imperial College London, London, United Kingdom.,4 Department of Clinical Engineering, Royal Brompton Hospital, London, United Kingdom
| | - Bradley A Edwards
- 1 Division of Sleep and Circadian Disorders and.,5 Sleep and Circadian Medicine Laboratory, Department of Physiology, and.,6 School of Psychological Sciences and Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Melbourne, Victoria, Australia
| | | | - Charlotte H Manisty
- 7 Institute of Cardiovascular Sciences, University College London, London, United Kingdom; and
| | - Akshay S Desai
- 8 Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | | | - Keith Willson
- 3 International Center for Circulatory Health, National Heart and Lung Institute, Imperial College London, London, United Kingdom
| | - Darrel P Francis
- 3 International Center for Circulatory Health, National Heart and Lung Institute, Imperial College London, London, United Kingdom
| | | | - Atul Malhotra
- 1 Division of Sleep and Circadian Disorders and.,9 Division of Pulmonary and Critical Care Medicine, University of California San Diego, La Jolla, California
| |
Collapse
|
|
36
|
Argerich S, Herrera S, Benito S, Giraldo BF. Evaluation of periodic breathing in respiratory flow signal of elderly patients using SVM and linear discriminant analysis. ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. ANNUAL INTERNATIONAL CONFERENCE 2017; 2016:4276-4279. [PMID: 28269227 DOI: 10.1109/embc.2016.7591672] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Aging population is a major concern that is reflected in the increase of chronic diseases. Heart Failure (HF) is one of the most common chronic diseases of elderly people that is punctuated with acute episodes, which result in hospitalization. The periodic modulation of the amplitude of the breathing pattern is proved to be one of the multiple symptoms of an acute episode, and thus, the features extracted from its characterization contribute in the improvement of the first diagnosis of the clinical practice. The main objective of this study is to evaluate if the features extracted from the breathing pattern along with common clinical variables are reliable enough to detect Periodic Breathing (PB). A dataset of 44 elderly patients containing clinical information and a short record of electrocardiogram and respiratory flow signal was used to train two machine learning classification methods: Support Vector Machine (SVM) and Linear Discriminant Analysis (LDA). All the available clinical parameters within the dataset along with the parameters characterizing the respiratory pattern were used to classify the observations into two groups. SVM classification was optimized and performed using a = -8 and C = 10.04 giving an accuracy of 88.2 % sensitivity of 90 % and specificity of 85.7 % Similar results were achieved with LDA classifying with an accuracy of 82.4 %, a sensitivity of 81.8% and specificity of 83.3 % PB has been accurately detected using both classifiers.
Collapse
|
|
37
|
Abstract
Central sleep apnea and Cheyne-Stokes respiration are commonly observed breathing patterns during sleep in patients with congestive heart failure. Common risk factors are male gender, older age, presence of atrial fibrillation, and daytime hypocapnia. Proposed mechanisms include augmented peripheral and central chemoreceptor sensitivity, which increase ventilator instability during both wakefulness and sleep; diminished cerebrovascular reactivity and increased circulation time, which impair the normal buffering of Paco2 and hydrogen ions and delay the detection of changes in Paco2 during sleep; and rostral fluid shifts that predispose to hypocapnia.
Collapse
|
|
38
|
Correale M, Carpagnano GE, Brunetti ND, Forte L, Monaco I, Ferraretti A, Sabato R, Barbaro MPF, Di Biase M, Lacedonia D. Respiratory drive in patients with chronic heart failure and central sleep apnea: Data from the Daunia Heart Failure Registry. Int J Cardiol 2017; 230:630-633. [PMID: 28065692 DOI: 10.1016/j.ijcard.2016.12.172] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2016] [Revised: 12/17/2016] [Accepted: 12/25/2016] [Indexed: 11/18/2022]
Affiliation(s)
| | | | | | - Lucia Forte
- Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Ilenia Monaco
- Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Armando Ferraretti
- Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | | | | | - Matteo Di Biase
- Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Donato Lacedonia
- Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| |
Collapse
|
|
39
|
Stewart Coats AJ. Early abnormalities of cerebral blood flow in mild non-ischaemic heart failure: part of a whole-body response? Eur J Heart Fail 2017; 19:269-270. [PMID: 28157270 DOI: 10.1002/ejhf.713] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2016] [Accepted: 11/14/2016] [Indexed: 12/28/2022] Open
|
|
40
|
Rocha A, Arbex FF, Alencar MCN, Sperandio PA, Hirai DM, Berton DC, O'Donnell DE, Neder JA. Physiological and sensory consequences of exercise oscillatory ventilation in heart failure-COPD. Int J Cardiol 2016; 224:447-453. [DOI: 10.1016/j.ijcard.2016.09.077] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2016] [Revised: 09/22/2016] [Accepted: 09/23/2016] [Indexed: 12/31/2022]
|
|
41
|
Cheyne-stokes respiration during wakefulness in patients with chronic heart failure. Sleep Breath 2016; 21:419-426. [DOI: 10.1007/s11325-016-1433-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2016] [Revised: 10/05/2016] [Accepted: 11/02/2016] [Indexed: 10/20/2022]
|
|
42
|
Autonomic outcome is better after endarterectomy than after stenting in patients with asymptomatic carotid stenosis. J Vasc Surg 2016; 64:975-84. [DOI: 10.1016/j.jvs.2016.04.040] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2016] [Accepted: 04/12/2016] [Indexed: 11/17/2022]
|
|
43
|
Abstract
Congestive heart failure (CHF) is among the most common causes of admission to hospitals in the United States, especially in those over age 65. Few data exist regarding the prevalence CHF of Cheyne-Stokes respiration (CSR) owing to congestive heart failure in the intensive care unit (ICU). Nevertheless, CSR is expected to be highly prevalent among those with CHF. Treatment should focus on the underlying mechanisms by which CHF increases loop gain and promotes unstable breathing. Few data are available to determine prevalence of CSR in the ICU, or how CSR might affect clinical management and weaning from mechanical ventilation.
Collapse
Affiliation(s)
- Scott A Sands
- Division of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA; Department of Allergy, Immunology and Respiratory Medicine and Central Clinical School, Alfred Hospital and Monash University, 55 Commercial Rd, Melbourne, VIC 3004, Australia
| | - Robert L Owens
- Division of Pulmonary and Critical Care Medicine, University of California San Diego, 9300 Campus Point Drive, #7381, La Jolla, CA 92037, USA.
| |
Collapse
|
|
44
|
Mozer MT, Holbein WW, Joyner MJ, Curry TB, Limberg JK. Reductions in carotid chemoreceptor activity with low-dose dopamine improves baroreflex control of heart rate during hypoxia in humans. Physiol Rep 2016; 4:e12859. [PMID: 27418545 PMCID: PMC4945841 DOI: 10.14814/phy2.12859] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2016] [Revised: 06/13/2016] [Accepted: 06/18/2016] [Indexed: 11/24/2022] Open
Abstract
The purpose of the present investigation was to examine the contribution of the carotid body chemoreceptors to changes in baroreflex control of heart rate with exposure to hypoxia. We hypothesized spontaneous cardiac baroreflex sensitivity (scBRS) would be reduced with hypoxia and this effect would be blunted when carotid chemoreceptor activity was reduced with low-dose dopamine. Fifteen healthy adults (11 M/4 F) completed two visits randomized to intravenous dopamine or placebo (saline). On each visit, subjects were exposed to 5-min normoxia (~99% SpO2), followed by 5-min hypoxia (~84% SpO2). Blood pressure (intra-arterial catheter) and heart rate (ECG) were measured continuously and scBRS was assessed by spectrum and sequence methodologies. scBRS was reduced with hypoxia (P < 0.01). Using the spectrum analysis approach, the fall in scBRS with hypoxia was attenuated with infusion of low-dose dopamine (P < 0.01). The decrease in baroreflex sensitivity to rising pressures (scBRS "up-up") was also attenuated with low-dose dopamine (P < 0.05). However, dopamine did not attenuate the decrease in baroreflex sensitivity to falling pressures (scBRS "down-down"; P > 0.05). Present findings are consistent with a reduction in scBRS with systemic hypoxia. Furthermore, we show this effect is partially mediated by the carotid body chemoreceptors, given the fall in scBRS is attenuated when activity of the chemoreceptors is reduced with low-dose dopamine. However, the improvement in scBRS with dopamine appears to be specific to rising blood pressures. These results may have important implications for impairments in baroreflex function common in disease states of acute and/or chronic hypoxemia, as well as the experimental use of dopamine to assess such changes.
Collapse
Affiliation(s)
- Michael T Mozer
- Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota
| | | | | | - Timothy B Curry
- Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota
| | | |
Collapse
|
|
45
|
Mirizzi G, Giannoni A, Ripoli A, Iudice G, Bramanti F, Emdin M, Passino C. Prediction of the Chemoreflex Gain by Common Clinical Variables in Heart Failure. PLoS One 2016; 11:e0153510. [PMID: 27099934 PMCID: PMC4839709 DOI: 10.1371/journal.pone.0153510] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2015] [Accepted: 03/30/2016] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Peripheral and central chemoreflex sensitivity, assessed by the hypoxic or hypercapnic ventilatory response (HVR and HCVR, respectively), is enhanced in heart failure (HF) patients, is involved in the pathophysiology of the disease, and is under investigation as a potential therapeutic target. Chemoreflex sensitivity assessment is however demanding and, therefore, not easily applicable in the clinical setting. We aimed at evaluating whether common clinical variables, broadly obtained by routine clinical and instrumental evaluation, could predict increased HVR and HCVR. METHODS AND RESULTS 191 patients with systolic HF (left ventricular ejection fraction--LVEF--<50%) underwent chemoreflex assessment by rebreathing technique to assess HVR and HCVR. All patients underwent clinical and neurohormonal evaluation, comprising: echocardiogram, cardiopulmonary exercise test (CPET), daytime cardiorespiratory monitoring for breathing pattern evaluation. Regarding HVR, multivariate penalized logistic regression, Bayesian Model Averaging (BMA) logistic regression and random forest analysis identified, as predictors, the presence of periodic breathing and increased slope of the relation between ventilation and carbon dioxide production (VE/VCO2) during exercise. Again, the above-mentioned statistical tools identified as HCVR predictors plasma levels of N-terminal fragment of proBNP and VE/VCO2 slope. CONCLUSIONS In HF patients, the simple assessment of breathing pattern, alongside with ventilatory efficiency during exercise and natriuretic peptides levels identifies a subset of patients presenting with increased chemoreflex sensitivity to either hypoxia or hypercapnia.
Collapse
Affiliation(s)
- Gianluca Mirizzi
- Department of Cardiology and Cardiovascular Medicine, Fondazione Toscana G. Monasterio, Pisa, Italy
- * E-mail:
| | - Alberto Giannoni
- Department of Cardiology and Cardiovascular Medicine, Fondazione Toscana G. Monasterio, Pisa, Italy
| | - Andrea Ripoli
- Department of Cardiology and Cardiovascular Medicine, Fondazione Toscana G. Monasterio, Pisa, Italy
| | - Giovanni Iudice
- Department of Cardiology and Cardiovascular Medicine, Fondazione Toscana G. Monasterio, Pisa, Italy
| | - Francesca Bramanti
- Department of Cardiology and Cardiovascular Medicine, Fondazione Toscana G. Monasterio, Pisa, Italy
| | - Michele Emdin
- Department of Cardiology and Cardiovascular Medicine, Fondazione Toscana G. Monasterio, Pisa, Italy
- Scuola Superiore Sant’Anna, Pisa, Italy
| | - Claudio Passino
- Department of Cardiology and Cardiovascular Medicine, Fondazione Toscana G. Monasterio, Pisa, Italy
- Scuola Superiore Sant’Anna, Pisa, Italy
| |
Collapse
|
|
46
|
Garde A, Sörnmo L, Laguna P, Jané R, Benito S, Bayés-Genís A, Giraldo BF. Assessment of respiratory flow cycle morphology in patients with chronic heart failure. Med Biol Eng Comput 2016; 55:245-255. [DOI: 10.1007/s11517-016-1498-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2014] [Accepted: 03/26/2016] [Indexed: 11/25/2022]
|
|
47
|
Dhakal BP, Lewis GD. Exercise oscillatory ventilation: Mechanisms and prognostic significance. World J Cardiol 2016; 8:258-266. [PMID: 27022457 PMCID: PMC4807314 DOI: 10.4330/wjc.v8.i3.258] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2015] [Accepted: 12/18/2015] [Indexed: 02/06/2023] Open
Abstract
Alteration in breathing patterns characterized by cyclic variation of ventilation during rest and during exercise has been recognized in patients with advanced heart failure (HF) for nearly two centuries. Periodic breathing (PB) during exercise is known as exercise oscillatory ventilation (EOV) and is characterized by the periods of hyperpnea and hypopnea without interposed apnea. EOV is a non-invasive parameter detected during submaximal cardiopulmonary exercise testing. Presence of EOV during exercise in HF patients indicates significant impairment in resting and exercise hemodynamic parameters. EOV is also an independent risk factor for poor prognosis in HF patients both with reduced and preserved ejection fraction irrespective of other gas exchange variables. Circulatory delay, increased chemosensitivity, pulmonary congestion and increased ergoreflex signaling have been proposed as the mechanisms underlying the generation of EOV in HF patients. There is no proven treatment of EOV but its reversal has been noted with phosphodiesterase inhibitors, exercise training and acetazolamide in relatively small studies. In this review, we discuss the mechanistic basis of PB during exercise and the clinical implications of recognizing PB patterns in patients with HF.
Collapse
|
|
48
|
Corrà U. Exercise oscillatory ventilation in heart failure. Int J Cardiol 2016; 206 Suppl:S13-5. [DOI: 10.1016/j.ijcard.2016.02.122] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2015] [Revised: 02/03/2016] [Accepted: 02/21/2016] [Indexed: 12/01/2022]
|
|
49
|
Flinta I, Ponikowski P. Relationship between central sleep apnea and Cheyne-Stokes Respiration. Int J Cardiol 2016; 206 Suppl:S8-12. [PMID: 26961739 DOI: 10.1016/j.ijcard.2016.02.124] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2015] [Accepted: 02/21/2016] [Indexed: 10/22/2022]
Abstract
Central sleep apnea (CSA) in patients with heart failure (HF) occurs frequently and shows a serious influence on prognosis in this population. The key elements in the pathophysiology of CSA are respiratory instability with chronic hyperventilation, changes of arterial carbon dioxide pressure (pCO2) and elongated circulation time. The main manifestation of CSA in patients with HF is Cheyne-Stokes Respiration (CSR). The initial treatment is the optimization of HF therapy. However, many other options of the therapeutic management have been studied, particularly those based on positive airway pressure methods. In patients with heart failure we often can observe the overlap of CSA and CSR; we will discuss the differences between these forms of breathing disorders during sleep. We will also discuss when CSA and CSR occur independently of each other and the importance of CSR occurring during the daytime in context of CSA during the nighttime.
Collapse
Affiliation(s)
- Irena Flinta
- Department of Cardiology, 4th Military Hospital, Wrocław, Poland; Department of Physiology, Medical University, Wrocław, Poland.
| | - Piotr Ponikowski
- Department of Cardiology, 4th Military Hospital, Wrocław, Poland; Clinic of Cardiac Diseases, Department of Heart Diseases, Medical University, Wrocław, Poland
| |
Collapse
|
|
50
|
Giannoni A, Raglianti V, Mirizzi G, Taddei C, Del Franco A, Iudice G, Bramanti F, Aimo A, Pasanisi E, Emdin M, Passino C. Influence of central apneas and chemoreflex activation on pulmonary artery pressure in chronic heart failure. Int J Cardiol 2016; 202:200-6. [DOI: 10.1016/j.ijcard.2015.09.007] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2015] [Revised: 08/16/2015] [Accepted: 09/06/2015] [Indexed: 10/23/2022]
|