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Soni S, Skow RJ, Foulkes S, Haykowsky MJ, Dyck JRB. Therapeutic potential of ketone bodies on exercise intolerance in heart failure: looking beyond the heart. Cardiovasc Res 2025; 121:230-240. [PMID: 39825790 PMCID: PMC12012446 DOI: 10.1093/cvr/cvaf004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Revised: 11/13/2024] [Accepted: 12/05/2024] [Indexed: 01/20/2025] Open
Abstract
Recent evidence suggests that ketone bodies have therapeutic potential in many cardiovascular diseases including heart failure (HF). Accordingly, this has led to multiple clinical trials that use ketone esters (KEs) to treat HF patients highlighting the importance of this ketone therapy. KEs, specifically ketone monoesters, are synthetic compounds which, when consumed, are de-esterified into two β-hydroxybutyrate (βOHB) molecules and increase the circulating βOHB concentration. While many studies have primarily focused on the cardiac benefits of ketone therapy in HF, ketones can have numerous favourable effects in other organs such as the vasculature and skeletal muscle. Importantly, vascular and skeletal muscle dysfunction are also heavily implicated in the reduced exercise tolerance, the hallmark feature in HF with reduced ejection fraction and preserved ejection fraction, suggesting that some of the benefits observed in HF in response to ketone therapy may involve these non-cardiac pathways. Thus, we review the evidence suggesting how ketone therapy may be beneficial in improving cardiovascular and skeletal muscle function in HF and identify various potential mechanisms that may be important in the beneficial non-cardiac effects of ketones in HF.
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Affiliation(s)
- Shubham Soni
- Cardiovascular Research Centre, University of Alberta, Edmonton, Alberta, Canada
- Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
| | - Rachel J Skow
- Integrated Cardiovascular and Exercise Physiology and Rehabilitation (iCARE) Lab, Faculty of Nursing, College of Health Sciences, University of Alberta, Edmonton, Alberta, Canada
| | - Stephen Foulkes
- Integrated Cardiovascular and Exercise Physiology and Rehabilitation (iCARE) Lab, Faculty of Nursing, College of Health Sciences, University of Alberta, Edmonton, Alberta, Canada
- Heart, Exercise and Research Trials Lab, St Vincent’s Institute of Medical Research, Fitzroy, Victoria, Australia
| | - Mark J Haykowsky
- Integrated Cardiovascular and Exercise Physiology and Rehabilitation (iCARE) Lab, Faculty of Nursing, College of Health Sciences, University of Alberta, Edmonton, Alberta, Canada
| | - Jason R B Dyck
- Cardiovascular Research Centre, University of Alberta, Edmonton, Alberta, Canada
- Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
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Iannetta D, Laginestra FG, Wray DW, Amann M. Dissecting the exercise pressor reflex in heart failure: A multi-step failure. Auton Neurosci 2025; 259:103269. [PMID: 40117701 DOI: 10.1016/j.autneu.2025.103269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Revised: 02/02/2025] [Accepted: 03/11/2025] [Indexed: 03/23/2025]
Abstract
The contribution of neural feedback originating from exercising limb muscles to the cardiovascular response to exercise was first recognized nearly 100 years ago. Today, it is well established that this influence is initiated by the activation of group III and IV sensory neurons with terminal endings located within contracting skeletal muscle. During exercise, these sensory neurons project feedback related to intramuscular mechanical and metabolic perturbations to medullary neural circuits which reflexively evoke decreases in parasympathetic and increases in sympathetic nervous system activity with the purpose of optimizing central and peripheral hemodynamics. Considerable evidence from animal and human studies suggests that the function of this regulatory control system, known as the exercise pressor reflex (EPR), is abnormal in heart failure and exaggerates sympatho-excitation which impairs the hemodynamic response to exercise and contributes to the functional limitations characterizing these patients. This review briefly introduces the key determinants of EPR control in health and covers the impact of heart failure on the integrity of each of its components and overall function. These include the sensitivity of group III/IV muscle afferents, afferent signal transmission in the spinal cord, and the central integration and processing of sensory feedback within the brainstem. Importantly, although most data relevant for this review come from studies in HFrEF, the limited HFpEF-specific insights are included when available. While arguably not part of the EPR, we also discuss the impact of heart failure on the exercise-induced increase of intramuscular stimuli of group III/IV muscle afferents and end-organ responsiveness to sympathetic/neurochemical stimulation.
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Affiliation(s)
- Danilo Iannetta
- Department of Anesthesiology, University of Utah, Salt Lake City, UT, United States of America; Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
| | | | - D Walter Wray
- Department of Internal Medicine, University of Utah, Salt Lake City, UT, United States of America; Geriatric Research, Education, and Clinical Center, VA Medical Center, Salt Lake City, UT, United States of America
| | - Markus Amann
- Department of Anesthesiology, University of Utah, Salt Lake City, UT, United States of America; Department of Internal Medicine, University of Utah, Salt Lake City, UT, United States of America; Geriatric Research, Education, and Clinical Center, VA Medical Center, Salt Lake City, UT, United States of America
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Kuwahara D, Umehara T, Kito N. Improvement of Physical Functions in Elderly Patients with Heart Failure Depends on the Hepatic Reserve. Phys Ther Res 2025; 28:45-53. [PMID: 40321685 PMCID: PMC12047040 DOI: 10.1298/ptr.e10328] [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: 11/11/2024] [Accepted: 01/27/2025] [Indexed: 05/08/2025]
Abstract
OBJECTIVES In recent years, the number of elderly heart failure patients with multiorgan failure has been increasing. Furthermore, the combination of heart failure and decreased hepatic reserve can cause severe skeletal muscle impairment and decreased survival rates. This study investigated whether the degree of improvement in the five repetitions of sit-to-stand (5STS) and walking speed (WS) differs depending on hepatic reserve in elderly heart failure patients. METHODS The patients were divided into the following two groups: good hepatic reserve (albumin-bilirubin score [ALBI score] ≤-2.25) and poor hepatic reserve (ALBI score >-2.25). Propensity score matching was performed using the brain natriuretic peptide level. A two-way analysis of variance (ANOVA) was performed to examine the main effects of the hepatic reserve and time points (admission or discharge). RESULTS After propensity score matching, 28 out of the 33 (84.8%) patients in the good hepatic reserve (age, 83.74 ± 9.25 years and ALBI score, -2.55 ± 0.19 points) and 27 out of 40 (67.5%)patients in the poor hepatic reserve (age, 85.85 ± 7.53 years and ALBI score, -1.93 ± 0.26 points) were analyzed. Two-way ANOVA showed that the 5STS (p = 0.04) and WS (p = 0.01) in poor hepatic reserve tended to be worse than in good hepatic reserve. Furthermore, the 5STS (p = 0.04) and WS tended to improve at discharge in both groups. However, the improvement in WS was not significant (p = 0.15). CONCLUSIONS Our study suggests that the hepatic reserve in elderly heart failure patients may be an important factor in the assessment of physical functions.
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Affiliation(s)
| | - Takuya Umehara
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Japan
| | - Nobuhiro Kito
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Japan
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Zeid S, Prochaska JH, Schuch A, Tröbs SO, Schulz A, Münzel T, Pies T, Dinh W, Michal M, Simon P, Wild PS. Personalized app-based coaching for improving physical activity in heart failure with preserved ejection fraction patients compared with standard care: rationale and design of the MyoMobile Study. EUROPEAN HEART JOURNAL. DIGITAL HEALTH 2025; 6:298-309. [PMID: 40110212 PMCID: PMC11914726 DOI: 10.1093/ehjdh/ztae096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Revised: 10/18/2024] [Accepted: 11/18/2024] [Indexed: 03/22/2025]
Abstract
Aims Patients suffering from heart failure with preserved ejection fraction (HFpEF) often exhibit a sedentary lifestyle, contributing to the worsening of their condition. Although there is an inverse relationship between physical activity (PA) and adverse cardiovascular outcomes, the implementation of Class Ia PA guidelines is hindered by low participation in supervised and structured programmes, which are not suitable for a diverse population of HFpEF patients. The MyoMobile study has been designed to assess the effect of a 12-week, app-based coaching programme on promoting PA in patients with HFpEF. Methods and results The MyoMobile study was a single-centre, randomized, controlled three-armed parallel group clinical trial with prospective data collection to investigate the effect of a personalized mobile app health intervention compared with usual care on PA levels in patients with HFpEF. Major inclusion criteria were age ≥ 45 years, a diagnosis of HFpEF, LVEF > 40%, and current HF symptoms (NYHA Class I-III). Major exclusion criteria included acute decompensated HF, non-ambulatory status, recent acute coronary syndrome or cardiac surgery, alternative diagnoses for HF symptoms, active cancer treatment, and physical or medical conditions affecting mobility. Participants were recruited from hospitals, general practices, and practices specialized in internal medicine and cardiology in the Rhine-Main area, Germany. Participants underwent an objective 7-day PA measurement with a 3D accelerometer (Dynaport, McRoberts) at screening and after the 12-week intervention period. Following the screening, eligible participants were randomized into one of three groups: standard care (PA consulting), the intervention arm with app-based PA tracking and coaching, or the intervention arm with tracking but without coaching. The primary efficacy endpoint was the change in average daily step count between the average step count at baseline and at the end of the intervention, comparing standard care to a 12-week app-based PA coaching intervention. Conclusion Exercise intolerance is a primary symptom in HFpEF patients, leading to poor quality of life and HF-related adverse outcomes due to physical inactivity. The MyoMobile study was designed to investigate the use of app-based coaching to improve PA in patients with HFpEF with a personalized, home-based intervention, focusing on simple step counts for flexibility and ease of integration into daily routines. Clinical trial registration URL: https://clinicaltrials.gov/ct2/show/NCT04940312. Unique identifier NCT04940312.
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Affiliation(s)
- Silav Zeid
- Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Langenbeckstraße 1, 55131 Mainz, Germany
| | - Jürgen H Prochaska
- Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Langenbeckstraße 1, 55131 Mainz, Germany
- Clinical Epidemiology and Systems Medicine, Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany
- Boehringer Ingelheim, Ingelheim am Rhein, Binger Str. 173, 55218 Ingelheim am Rhein, Germany
| | - Alexander Schuch
- Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Langenbeckstraße 1, 55131 Mainz, Germany
| | - Sven Oliver Tröbs
- Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Langenbeckstraße 1, 55131 Mainz, Germany
- Boehringer Ingelheim, Ingelheim am Rhein, Binger Str. 173, 55218 Ingelheim am Rhein, Germany
| | - Andreas Schulz
- Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany
| | - Thomas Münzel
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Langenbeckstraße 1, 55131 Mainz, Germany
- Department of Cardiology - Cardiology I, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany
| | - Tanja Pies
- Bayer AG, Friedrich-Ebert-Straße 217/333, 42117 Wuppertal, Germany
| | - Wilfried Dinh
- Bayer AG, Friedrich-Ebert-Straße 217/333, 42117 Wuppertal, Germany
- Institute for Cardiovascular Research, University of Witten/Herdecke, Alfred-Herrhausen-Straße 50, 58455 Witten, Germany
- Department of Cardiology, HELIOS Clinic Wuppertal, Arrenberger Str. 20, 42117 Wuppertal, Germany
| | - Matthias Michal
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Langenbeckstraße 1, 55131 Mainz, Germany
- Department of Psychosomatic Medicine and Psychotherapy, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany
| | - Perikles Simon
- Department of Sports Medicine, Rehabilitation and Disease Prevention, Faculty of Social Science, Media and Sport, Johannes Gutenberg-University Mainz, Albert-Schweitzer-Straße 22, 55128 Mainz, Germany
| | - Philipp Sebastian Wild
- Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Langenbeckstraße 1, 55131 Mainz, Germany
- Clinical Epidemiology and Systems Medicine, Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany
- Systems Medicine Group, Institute of Molecular Biology (IMB), Ackermannweg 4, 55128 Mainz, Germany
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Takeshita H, Yamamoto K, Mogi M, Rakugi H. Muscle mass, muscle strength and the renin-angiotensin system. Clin Sci (Lond) 2024; 138:1561-1577. [PMID: 39718491 DOI: 10.1042/cs20220501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 11/19/2024] [Accepted: 11/25/2024] [Indexed: 12/25/2024]
Abstract
The renin-angiotensin system (RAS) is a classically known circulatory regulatory system. In addition to the previously known multi-organ circulatory form of the RAS, the existence of tissue RASs in individual organs has been well established. Skeletal muscle has also been identified as an organ with a distinct RAS. In recent years, the effects of RAS activation on skeletal muscle have been elucidated from several perspectives: differences in motor function due to genetic polymorphisms of RAS components, skeletal muscle dysfunction under conditions of excessive RAS activation such as heart failure, and the effects of the use of RAS inhibitors on muscle strength. In addition, the concept of the RAS itself has recently been expanded with the discovery of a 'protective arm' of the RAS formed by factors such as angiotensin-converting enzyme 2 and angiotensin 1-7. This has led to a new understanding of the physiological function of the RAS in skeletal muscle. This review summarizes the diverse physiological functions of the RAS in skeletal muscle and considers the potential of future therapeutic strategies targeting the RAS to overcome problems such as sarcopenia and muscle weakness associated with chronic disease.
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Affiliation(s)
- Hikari Takeshita
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
- Department of Medical Science Technology, Faculty of Medical Science Technology, Morinomiya University of Medical Sciences, Osaka, Osaka, Japan
| | - Koichi Yamamoto
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Masaki Mogi
- Department of Pharmacology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
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Winner G J, Jain S, Gupta D. Unveiling novel molecules and therapeutic targets in hypertension - A narrative review. Eur J Pharmacol 2024; 984:177053. [PMID: 39393666 DOI: 10.1016/j.ejphar.2024.177053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 09/18/2024] [Accepted: 10/07/2024] [Indexed: 10/13/2024]
Abstract
Hypertension is a prevalent non-communicable disease with serious cardiovascular complications, including heart failure, myocardial infarction, and stroke, often resulting from uncontrolled hypertension. While current treatments primarily target the renin-angiotensin-aldosterone pathway, the therapeutic response remains modest in many patients, with some developing resistant hypertension. Newer therapeutic approaches aim to address hypertension from various aspects beyond conventional drugs, including targeting central nervous system pathways, inflammatory pathways, vascular smooth muscle function, and baroreceptors. Despite these advancements, each therapy faces unique clinical and mechanistic challenges that influence its clinical translatability and long-term viability. This review explores the mechanisms of novel molecules in preclinical and clinical development, highlights potential therapeutic targets, and discusses the challenges and ethical considerations related to hypertension therapeutics and their development.
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Affiliation(s)
| | - Surbhi Jain
- Aligarh Muslim University, Uttar Pradesh, India
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Kaneguchi A, Sakitani N, Umehara T. Histological changes in skeletal muscle induced by heart failure in human patients and animal models: A scoping review. Acta Histochem 2024; 126:152210. [PMID: 39442432 DOI: 10.1016/j.acthis.2024.152210] [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: 07/27/2024] [Revised: 10/15/2024] [Accepted: 10/15/2024] [Indexed: 10/25/2024]
Abstract
OBJECTIVE This scoping review aimed to characterize the histological changes in skeletal muscle after heart failure (HF) and to identify gaps in knowledge. METHODS On April 03, 2024, systematic searches were performed for papers in which histological analyses were conducted on skeletal muscle sampled from patients with HF or animal models of HF. Screening and data extraction were conducted by two independent authors. RESULTS AND CONCLUSION A total of 118 papers were selected, including 33 human and 85 animal studies. Despite some disagreements among studies, some trends were observed. These trends included a slow-to-fast transition, a decrease in muscle fiber size, capillary to muscle fiber ratio, and mitochondrial activity and content, and an increase in apoptosis. These changes may contribute to the fatigability and decrease in muscle strength observed after HF. Although there were some disagreements between the results of human and animal studies, the results were generally similar. Animal models of HF will therefore be useful in elucidating the histological changes in skeletal muscle that occur in human patients with HF. Because the muscles subjected to histological analysis were mostly thigh muscles in humans and mostly lower leg muscles in animals, it remains uncertain whether changes similar to those seen in lower limb (hindlimb) muscles after HF also occur in upper limb (forelimb) muscles. The results of this review will consolidate the current knowledge on HF-induced histological changes in skeletal muscle and consequently aid in the rehabilitation of patients with HF and future studies.
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Affiliation(s)
- Akinori Kaneguchi
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose-Gakuendai 555-36, Higashi-Hiroshima, Hiroshima, 739-2695, Japan.
| | - Naoyoshi Sakitani
- Department of Life Science and Biotechnology, National Institute of Advanced Industrial Science and Technology, Hayashi-cho 2217-4, Takamatsu, Kagawa, 761-0395, Japan
| | - Takuya Umehara
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose-Gakuendai 555-36, Higashi-Hiroshima, Hiroshima, 739-2695, Japan
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Shibata A, Izumiya Y, Yoshida T, Tanihata A, Kitada R, Otsuka K, Ito A, Yamazaki T, Fukuda D. Effect of tafamidis therapy on physical function in patients with wild-type transthyretin cardiac amyloidosis. J Cardiol 2024:S0914-5087(24)00217-X. [PMID: 39613156 DOI: 10.1016/j.jjcc.2024.11.004] [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: 08/27/2024] [Revised: 10/23/2024] [Accepted: 11/07/2024] [Indexed: 12/01/2024]
Abstract
BACKGROUND Tafamidis is used as disease-modifying treatment for patients with wild-type transthyretin cardiac amyloidosis (ATTRwt CA). However, the effects of tafamidis on exercise tolerance are unclear. METHODS This single-center, prospective, observational study aimed to assess the effect of tafamidis on exercise tolerance in 36 patients with ATTRwt CA. Exercise tolerance was evaluated by the peak oxygen uptake (peak VO2) measured by the cardiopulmonary exercise test (CPX). RESULTS The baseline CPX showed a mean anaerobic threshold value of 11.6 ± 2.2 ml/kg/min and peak VO2 of 15.6 ± 4.1 ml/kg/min. Twenty-eight of the 36 patients underwent a follow-up CPX after 6 months. There was no significant change in peak VO2 before and 6 months after tafamidis therapy (16.0 ± 4.2 vs. 14.7 ± 4.0 ml/kg/min). The baseline CPX data showed that the mean peak VO2 was significantly lower in the increased peak VO2 group than in the non-increased peak VO2 group (13.7 ± 3.1 vs. 17.7 ± 4.1 ml/kg/min, p = 0.008). A multivariate logistic regression analysis showed that the baseline peak VO2 value was an independent predictor of improved exercise tolerance by tafamidis therapy (odds ratio: 0.646, 95 % confidence interval: 0.449-0.930, p = 0.019). CONCLUSIONS Tafamidis prevents deterioration of exercise tolerance in patients with ATTRwt CA. In some patients with ATTRwt CA, exercise tolerance may improve with the use of tafamidis, and those with lower exercise tolerance before tafamidis administration are likely to show improved exercise tolerance.
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Affiliation(s)
- Atsushi Shibata
- Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Yasuhiro Izumiya
- Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
| | - Toshitake Yoshida
- Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Akiko Tanihata
- Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Ryoko Kitada
- Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Kenichiro Otsuka
- Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Asahiro Ito
- Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Takanori Yamazaki
- Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Daiju Fukuda
- Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
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Schmid V, Foulkes SJ, Walesiak D, Wang J, Tomczak CR, Tucker WJ, Angadi SS, Halle M, Haykowsky MJ. Impact of whole-body and skeletal muscle composition on peak oxygen uptake in heart failure: a systematic review and meta-analysis. EUROPEAN HEART JOURNAL OPEN 2024; 4:oeae082. [PMID: 39464232 PMCID: PMC11505452 DOI: 10.1093/ehjopen/oeae082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 09/15/2024] [Accepted: 09/24/2024] [Indexed: 10/29/2024]
Abstract
Aims Heart failure (HF) has a major impact on exercise tolerance that may (in part) be due to abnormalities in body and skeletal muscle composition. This systematic review and meta-analysis aims to assess how differences in whole-body and skeletal muscle composition between patients with HF and non-HF controls (CON) contribute to reduced peak oxygen uptake (VO2peak). Methods and results The PubMed database was searched from 1975 to May 2024 for eligible studies. Cross-sectional studies with measures of VO2peak, body composition, or muscle biopsies in HF and CON were considered. Out of 709 articles, 27 studies were included in this analysis. Compared with CON, VO2peak [weighted mean difference (WMD): -9.96 mL/kg/min, 95% confidence interval (CI): -11.71 to -8.21), total body lean mass (WMD: -1.63 kg, 95% CI: -3.05 to -0.21), leg lean mass (WMD: -1.38 kg, 95% CI: -2.18 to -0.59), thigh skeletal muscle area (WMD: -10.88 cm2 , 95% CI: -21.40 to -0.37), Type I fibres (WMD: -7.76%, 95% CI: -14.81 to -0.71), and capillary-to-fibre ratio (WMD: -0.27, 95% CI: -0.50 to -0.03) were significantly lower in HF. Total body fat mass (WMD: 3.34 kg, 95% CI: 0.35-6.34), leg fat mass (WMD: 1.37 kg, 95% CI: 0.37-2.37), and Type IIx fibres (WMD: 7.72%, 95% CI: 1.52-13.91) were significantly higher in HF compared with CON. Absolute VO2peak was significantly associated with total body and leg lean mass, thigh skeletal muscle area, and capillary-to-fibre ratio. Conclusion Individuals with HF display abnormalities in body and skeletal muscle composition including reduced lean mass, oxidative Type I fibres, and capillary-to-fibre ratio that negatively impact VO2peak.
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Affiliation(s)
- Veronika Schmid
- Department for Preventive Sports Medicine and Sports Cardiology, TUM University Hospital, School of Medicine and Health, Technical University of Munich, Georg-Brauchle-Ring 56, 80992 Munich, Germany
- Integrated Cardiovascular Exercise Physiology and Rehabilitation Lab, Faculty of Nursing, College of Health Science, University of Alberta, 3-045/11405 87 Ave NW, Edmonton, T6G IC9 Alberta, Canada
| | - Stephen J Foulkes
- Integrated Cardiovascular Exercise Physiology and Rehabilitation Lab, Faculty of Nursing, College of Health Science, University of Alberta, 3-045/11405 87 Ave NW, Edmonton, T6G IC9 Alberta, Canada
- Heart, Exercise and Research Trials Lab, St Vincent’s Institute of Medical Research, 9 Princes Street, Fitzroy, 3065 Victoria, Australia
| | - Devyn Walesiak
- Integrated Cardiovascular Exercise Physiology and Rehabilitation Lab, Faculty of Nursing, College of Health Science, University of Alberta, 3-045/11405 87 Ave NW, Edmonton, T6G IC9 Alberta, Canada
| | - Jing Wang
- Division of Public Health, School of Medicine, University of Utah, 375 Chipeta Way, UT 84108 Salt Lake City, USA
| | - Corey R Tomczak
- College of Kinesiology, University of Saskatchewan, 87 Campus Dr, Saskatoon, S7N 5B2 Saskatchewan, Canada
| | - Wesley J Tucker
- Department of Nutrition and Food Sciences, Texas Woman’s University, 304 Administration Dr. Denton, TX 76204 Houston, USA
| | - Siddhartha S Angadi
- Department of Kinesiology, University of Virginia, 405 Emmet Street, VA 22903 Charlottesville, USA
| | - Martin Halle
- Department for Preventive Sports Medicine and Sports Cardiology, TUM University Hospital, School of Medicine and Health, Technical University of Munich, Georg-Brauchle-Ring 56, 80992 Munich, Germany
- DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Bavaria, Germany
| | - Mark J Haykowsky
- Integrated Cardiovascular Exercise Physiology and Rehabilitation Lab, Faculty of Nursing, College of Health Science, University of Alberta, 3-045/11405 87 Ave NW, Edmonton, T6G IC9 Alberta, Canada
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Kourek C, Zachariou A, Karatzanos E, Antonopoulos M, Soulele T, Karabinis A, Nanas S, Dimopoulos S. Effects of combined aerobic, resistance and inspiratory training in patients with pulmonary hypertension: A systematic review. World J Crit Care Med 2024; 13:92585. [PMID: 38855278 PMCID: PMC11155510 DOI: 10.5492/wjccm.v13.i2.92585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 04/29/2024] [Accepted: 05/21/2024] [Indexed: 06/03/2024] Open
Abstract
BACKGROUND Pulmonary hypertension (PH) is a serious progressive disorder of the modern world, characterized by endothelial dysfunction and impaired vasoreactivity. Patients with PH usually present exercise intolerance from the very early stages and reduced exercise capacity. Exercise training has been shown to have beneficial effects in patients with cardiovascular comorbidities. However, data regarding the effects of combined exercise training programs in patients with PH still remains limited. AIM To investigate the effects of combined exercise training programs on exercise capacity and quality of life in patients with PH. METHODS Our search included all available randomized controlled trials (RCTs) regarding combined aerobic, resistance and inspiratory training programs in patients with PH in 4 databases (Pubmed, PEDro, Embase, CINAHL) from 2012 to 2022. Five RCTs were included in the final analysis. Functional capacity, assessed by peak VO2 or 6-min walking test (6MWT), as well as quality of life, assessed by the SF-36 questionnaire, were set as the primary outcomes in our study. RESULTS Peak VO2 was measured in 4 out of the 5 RCTs while 6MWT was measured in all RCTs. Both indices of functional capacity were significantly increased in patients with PH who underwent combined exercise training compared to the controls in all of the included RCTs (P < 0.05). Quality of life was measured in 4 out of 5 RCTs. Although patients improved their quality of life in each group, however, only 2 RCTs demonstrated further improvement in patients performing combined training compared to controls. CONCLUSION By this systematic review, we have demonstrated that combined aerobic, resistance and inspiratory exercise training is safe and has beneficial effects on aerobic capacity and quality of life in patients with PH. Such exercise training regimen may be part of the therapeutic strategy of the syndrome.
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Affiliation(s)
- Christos Kourek
- Department of Clinical Ergospirometry, Exercise and Rehabilitation Laboratory, 1st Department of Critical Care Medicine, Evangelismos Hospital, National and Kapodistrian University of Athens, Athens 10676, Greece
- Department of Cardiology, 417 Army Share Fund Hospital of Athens, Athens 11521, Greece
| | - Antonia Zachariou
- Department of Clinical Ergospirometry, Exercise and Rehabilitation Laboratory, 1st Department of Critical Care Medicine, Evangelismos Hospital, National and Kapodistrian University of Athens, Athens 10676, Greece
| | - Eleftherios Karatzanos
- Department of Clinical Ergospirometry, Exercise and Rehabilitation Laboratory, 1st Department of Critical Care Medicine, Evangelismos Hospital, National and Kapodistrian University of Athens, Athens 10676, Greece
| | - Michalis Antonopoulos
- Department of Clinical Ergospirometry, Exercise and Rehabilitation Laboratory, 1st Department of Critical Care Medicine, Evangelismos Hospital, National and Kapodistrian University of Athens, Athens 10676, Greece
- Cardiac Surgery ICU, Onassis Cardiac Surgery center, Athens 17674, Attica, Greece
| | - Theodora Soulele
- Cardiac Surgery ICU, Onassis Cardiac Surgery Center, Athens 17674, Greece
| | - Andreas Karabinis
- Cardiac Surgery Intensive Care Unit, Onassis Cardiac Surgery Center, Athens 17674, Greece
| | - Serafim Nanas
- Department of Clinical Ergospirometry, Exercise and Rehabilitation Laboratory, National and Kapodistrian University of Athens, Athens 10676, Greece
| | - Stavros Dimopoulos
- Department of Clinical Ergospirometry, Exercise and Rehabilitation Laboratory, 1st Department of Critical Care Medicine, Evangelismos Hospital, National and Kapodistrian University of Athens, Athens 10676, Greece
- Cardiac Surgery ICU, Onassis Cardiac Surgery Center, Athens 17674, Greece
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11
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Tanihata A, Shibata A, Yoshida T, Kitada R, Izumiya Y, Fukuda D. Hemoglobin is an independent predictor of improvement exercise tolerance in male patients with non-ischemic cardiomyopathy. Heart Vessels 2024; 39:412-426. [PMID: 38411633 DOI: 10.1007/s00380-024-02358-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Accepted: 01/10/2024] [Indexed: 02/28/2024]
Abstract
Exercise intolerance is a symptom of chronic heart failure (CHF). The magnitude of exercise tolerance, as measured by peak oxygen uptake (peak VO2), is strongly associated with prognosis in patients with CHF. We aimed to evaluate the factors associated with improved exercise tolerance in patients with HF. In this prospective study, we recruited patients who were diagnosed with non-ischemic cardiomyopathy between September 2017 and September 2021. All patients underwent cardiopulmonary exercise testing at discharge and 6 months after enrollment. The patients were stratified according to whether peak VO2 was increased or not at 6 months. One hundred patients with a reduced left-ventricular ejection fraction (LVEF < 50%) were enrolled. Improvement of peak VO2 was observed in 74 patients. In male patients, hemoglobin level was higher in the increased peak VO2 group than in the non-increased group (15.0 ± 1.9 g/dL vs. 13.1 ± 2.1 g/dL; p < 0.01). Baseline hemoglobin level was positively correlated with the percentage change in peak VO2 (Spearman's r = 0.248, p = 0.040). Kaplan-Meier analysis demonstrated that adverse cardiac events were significantly less frequent in the increased peak VO2 group than in the non-increased group (log-rank test, p = 0.032). Multivariate logistic regression analysis identified hemoglobin level as an independent predictor of improved peak VO2 [odds ratio (OR) 1.60; 95% confidence interval (CI) 1.05-2.44; p = 0.027]. Baseline hemoglobin level is an independent predictor of improved peak VO2 in male patients with non-ischemic cardiomyopathy.
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Affiliation(s)
- Akiko Tanihata
- Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan
| | - Atsushi Shibata
- Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
| | - Toshitake Yoshida
- Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan
| | - Ryoko Kitada
- Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan
| | - Yasuhiro Izumiya
- Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan
| | - Daiju Fukuda
- Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan
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12
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Uchida S, Kamiya K, Hamazaki N, Nozaki K, Ichikawa T, Yamashita M, Noda T, Ueno K, Hotta K, Maekawa E, Yamaoka-Tojo M, Matsunaga A, Ako J. The Association between the Level of Ankle-Brachial Index and the Risk of Poor Physical Function in Patients with Cardiovascular Disease. J Atheroscler Thromb 2024; 31:419-428. [PMID: 38044086 PMCID: PMC10999722 DOI: 10.5551/jat.64531] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Accepted: 09/26/2023] [Indexed: 12/05/2023] Open
Abstract
AIMS The progression of atherosclerosis and decline in physical function are poor prognostic factors in patients with cardiovascular disease (CVD). The ankle-brachial index (ABI) is a widely used indicator of the degree of progression of atherosclerosis, which may be used to identify patients with CVD who are at risk of poor physical function. This study examined the association between ABI and poor physical function in patients with CVD. METHODS We reviewed the data of patients with CVD who completed the ABI assessment and physical function tests (6-min walking distance, gait speed, quadriceps isometric strength, and short physical performance battery). Patients were divided into five categories according to the level of ABI, and the association between ABI and poor physical function was examined using multiple logistic regression analysis. Additionally, restricted cubic splines were used to examine the nonlinear association between ABI and physical function. RESULTS A total of 2982 patients (median [interquartile range] age: 71[62-78] years, 65.8% males) were included in this study. Using an ABI range of 1.11-1.20 as a reference, logistic regression analysis showed that ABI ≤ 1.10 was associated with poor physical function. The restricted cubic spline analysis showed that all physical functions increased with an increase in ABI level. The increase in physical function plateaued at an ABI level of approximately 1.1. CONCLUSIONS ABI may be used to identify patients with poor physical function. ABI levels below 1.1 are potentially associated with poor physical function in patients with CVD.
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Affiliation(s)
- Shota Uchida
- Department of Rehabilitation Sciences, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan
- Research Fellow of Japan Society for the Promotion of Science, Tokyo, Japan
| | - Kentaro Kamiya
- Department of Rehabilitation Sciences, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan
- Department of Rehabilitation, Kitasato University School of Allied Health Sciences, Sagamihara, Japan
| | - Nobuaki Hamazaki
- Department of Rehabilitation, Kitasato University Hospital, Sagamihara, Japan
| | - Kohei Nozaki
- Department of Rehabilitation, Kitasato University Hospital, Sagamihara, Japan
| | - Takafumi Ichikawa
- Department of Rehabilitation, Kitasato University Hospital, Sagamihara, Japan
| | - Masashi Yamashita
- Department of Rehabilitation Sciences, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan
- Division of Research, ARCE Inc., Sagamihara, Japan
| | - Takumi Noda
- Department of Rehabilitation Sciences, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan
- Exercise Physiology and Cardiovascular Health Lab, Division of Cardiac Prevention and Rehabilitation, University of Ottawa Heart Institute, Ottawa, Canada
| | - Kensuke Ueno
- Department of Rehabilitation Sciences, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan
| | - Kazuki Hotta
- Department of Rehabilitation Sciences, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan
- Department of Rehabilitation, Kitasato University School of Allied Health Sciences, Sagamihara, Japan
| | - Emi Maekawa
- Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan
| | - Minako Yamaoka-Tojo
- Department of Rehabilitation Sciences, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan
- Department of Rehabilitation, Kitasato University School of Allied Health Sciences, Sagamihara, Japan
| | - Atsuhiko Matsunaga
- Department of Rehabilitation Sciences, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan
- Department of Rehabilitation, Kitasato University School of Allied Health Sciences, Sagamihara, Japan
| | - Junya Ako
- Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan
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13
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Sadek Z, Ramadan W, Ahmaidi S, Youness M, Joumaa WH. Electromyogram Power Spectrum and Cardiac Function Changes After Combined Aerobic Interval Training and Inspiratory Muscle Training in Chronic Heart Failure Patients. Int Heart J 2024; 65:71-83. [PMID: 38296582 DOI: 10.1536/ihj.23-326] [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] [Indexed: 02/07/2024]
Abstract
Exercise intolerance and dyspnea are the major symptoms of patients with chronic heart failure (CHF) and are associated with a poor quality of life. In addition to impaired central hemodynamics, symptoms may be attributed to changes in peripheral skeletal muscles. This study aimed to evaluate the effects of aerobic interval training (AIT) combined with inspiratory muscle training (IMT) on cardiac and skeletal muscle function and on functional capacity and dyspnea in patients with CHF and inspiratory muscle weakness.Left ventricle ejection fraction was improved significantly after AIT and AIT & IMT with a high percentage of amelioration (17%, P < 0.042) in the combined group compared to the control group. Therefore, we showed a significant improvement in maximal voluntary isometric force, isometric endurance time, root mean square, and frequency median in both strength and endurance manipulations in the aerobic and combined group; however, the improvement was superior in the combined group compared to the control group. Significant amelioration was proved in functional capacity and dyspnea after all types of training but was performed at 18% higher in 6 minutes' walk test and 43% lower in dyspnea for the combined group compared to the control group.Combining AIT to IMT had optimized exercise training benefits in reversing the cardiac remodeling process and improving skeletal muscle function, functional capacity, and dyspnea in patients with CHF.
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Affiliation(s)
- Zahra Sadek
- Laboratory EA-3300 (APERE), Adaptations Physiologiques à l'Exercice et Réadaptation à l'Effort, Picardie Jules Verne University
- Rammal Hassan Rammal Laboratory, PhyToxE Physio-toxicité environnemental, Faculty of Sciences, Lebanese University
| | - Wiam Ramadan
- Rammal Hassan Rammal Laboratory, PhyToxE Physio-toxicité environnemental, Faculty of Sciences, Lebanese University
- Lebanese Institutes for Biomedical Research and Application (LIBRA), Lebanese International University (LIU)
| | - Said Ahmaidi
- Laboratory EA-3300 (APERE), Adaptations Physiologiques à l'Exercice et Réadaptation à l'Effort, Picardie Jules Verne University
| | | | - Wissam H Joumaa
- Rammal Hassan Rammal Laboratory, PhyToxE Physio-toxicité environnemental, Faculty of Sciences, Lebanese University
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14
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Buchanan C, Buchanan C, Riordan M, Byrd J, Schulte M, Kohrt WM, Ambardekar AV, Allen LA, Wolfel G, Lawley J, Levine BD, Cornwell WK. Cardiopulmonary Performance Among Heart Failure Patients Before and After Left Ventricular Assist Device Implantation. JACC. HEART FAILURE 2024; 12:117-129. [PMID: 37632493 DOI: 10.1016/j.jchf.2023.06.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Revised: 06/01/2023] [Accepted: 06/06/2023] [Indexed: 08/28/2023]
Abstract
BACKGROUND Patients with heart failure with reduced ejection fraction (HFrEF) have persistent impairments in functional capacity after continuous-flow left ventricular assist device (CF-LVAD) implantation. OBJECTIVES This study aims to characterize longitudinal changes in exercise hemodynamics and functional capacity among patients with HFrEF before and after CF-LVAD implantation. METHODS Ten patients underwent 3 invasive cardiopulmonary exercise tests on upright cycle ergometry with pulmonary artery catheterization: 1) Visit 1 before CF-LVAD implantation; 2) Visit 2 after device implantation with CF-LVAD pump speed held constant at baseline speed; and 3) Visit 3 with increases in pump speed during exercise (median: 1,050 rpm [IQR: 750-1,150 rpm] and 220 rpm [IQR: 120-220 rpm] for HeartMate 3 and HeartWare VAD, respectively). Hemodynamics and direct Fick cardiac output were monitored using pulmonary artery catheterization. Gas exchange metrics were determined using indirect calorimetry. RESULTS Maximal oxygen uptake (Visits 1, 2, and 3: 10.8 ± 2.5 mL/kg/min, 10.7 ± 2.2 mL/kg/min, and 11.5 ± 1.7 mL/kg/min; P = 0.92) did not improve after device implantation. Mean pulmonary arterial and pulmonary capillary wedge pressures increased significantly during submaximal and peak exercise on preimplantation testing (P < 0.01 for rest vs peak exercise) and remained elevated, with minimal change on Visits 2 and 3 regardless of whether pump speed was fixed or increased. CONCLUSIONS Among patients with HFrEF, cardiovascular hemodynamics and exercise capacity were similar after CF-LVAD implantation, regardless of whether patients exercised at fixed or adjusted pump speeds during exercise. Further research is needed to determine methods by which LVADs may alleviate the HFrEF syndrome after device implantation. (Effect of mechanIcal circulatoRy support ON exercise capacity aMong pAtieNts with heart failure [IRONMAN]; NCT03078972).
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Affiliation(s)
- Cole Buchanan
- Department of Internal Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Collen Buchanan
- Department of Internal Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Maeveen Riordan
- Department of Internal Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Jessica Byrd
- Department of Medicine-Cardiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Margaret Schulte
- Colorado Clinical and Translational Sciences Institute, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Wendy M Kohrt
- Colorado Clinical and Translational Sciences Institute, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; Department of Medicine-Geriatric Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Amrut V Ambardekar
- Department of Medicine-Cardiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Larry A Allen
- Department of Medicine-Cardiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Gene Wolfel
- Department of Medicine-Cardiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Justin Lawley
- Department of Sport Science, Division of Physiology, University of Innsbruck, Innsbruck, Austria
| | - Benjamin D Levine
- Department of Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, and the Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Dallas, Dallas, Texas, USA
| | - William K Cornwell
- Department of Medicine-Cardiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; Colorado Clinical and Translational Sciences Institute, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
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15
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Serrano N, Hyatt JPK, Houmard JA, Murgia M, Katsanos CS. Muscle fiber phenotype: a culprit of abnormal metabolism and function in skeletal muscle of humans with obesity. Am J Physiol Endocrinol Metab 2023; 325:E723-E733. [PMID: 37877797 PMCID: PMC10864022 DOI: 10.1152/ajpendo.00190.2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 10/23/2023] [Accepted: 10/23/2023] [Indexed: 10/26/2023]
Abstract
The proportion of the different types of fibers in a given skeletal muscle contributes to its overall metabolic and functional characteristics. Greater proportion of type I muscle fibers is associated with favorable oxidative metabolism and function of the muscle. Humans with obesity have a lower proportion of type I muscle fibers. We discuss how lower proportion of type I fibers in skeletal muscle of humans with obesity may explain metabolic and functional abnormalities reported in these individuals. These include lower muscle glucose disposal rate, mitochondrial content, protein synthesis, and quality/contractile function, as well as increased risk for heart disease, lower levels of physical activity, and propensity for weight gain/resistance to weight loss. We delineate future research directions and the need to examine hybrid muscle fiber populations, which are indicative of a transitory state of fiber phenotype within skeletal muscle. We also describe methodologies for precisely characterizing muscle fibers and gene expression at the single muscle fiber level to enhance our understanding of the regulation of muscle fiber phenotype in obesity. By contextualizing research in the field of muscle fiber type in obesity, we lay a foundation for future advancements and pave the way for translation of this knowledge to address impaired metabolism and function in obesity.
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Affiliation(s)
- Nathan Serrano
- School of Life Sciences, Arizona State University, Tempe, Arizona, United States
| | - Jon-Philippe K Hyatt
- College of Integrative Sciences and Arts, Arizona State University, Tempe, Arizona, United States
| | - Joseph A Houmard
- Department of Kinesiology, Human Performance Laboratory, East Carolina University, Greenville, North Carolina, United States
| | - Marta Murgia
- Department of Biomedical Sciences, University of Padova, Padua, Italy
- Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Martinsried, Germany
| | - Christos S Katsanos
- School of Life Sciences, Arizona State University, Tempe, Arizona, United States
- Department of Physiology and Biomedical Engineering, Mayo Clinic-Arizona, Phoenix, Arizona, United States
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16
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Nelson RK, Solomon R, Hosmer E, Zuhl M. Cardiac rehabilitation utilization, barriers, and outcomes among patients with heart failure. Heart Fail Rev 2023; 28:1239-1249. [PMID: 37039955 DOI: 10.1007/s10741-023-10309-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/27/2023] [Indexed: 04/12/2023]
Abstract
Exercise-based cardiac rehabilitation (CR) is effective for improving both primary (i.e., mortality and hospitalizations) and secondary (i.e., functional capacity and quality of life among) clinical outcomes among patients with heart failure (HF). The mechanisms that explain these benefits are complex and are linked to exercise adaptations such as central and peripheral hemodynamics combined with improved overall medical management. Despite the benefits of CR, utilization rates are low among CR eligible patients. Clinician-, patient-, and health system-related barriers have been identified as primary factors contributing to the lack of CR utilization among HF patients. These include patient referrals (clinician-related), psychosocial factors (patient-related), and patient access to CR services (health system-related). The aims of this review are to detail the components of each barrier as well as identify evidence-based strategies to improve CR utilization and adherence among HF. The improvements in primary and secondary outcomes along with the mechanisms that are linked to these changes will also be examined.
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Affiliation(s)
- Rachael K Nelson
- School of Health Sciences, Central Michigan University, Mt. Pleasant, MI, USA
| | - Robert Solomon
- Department of Cardiology, Henry Ford Hospital, Detroit, MI, USA
| | - Emily Hosmer
- School of Health Sciences, Central Michigan University, Mt. Pleasant, MI, USA
| | - Micah Zuhl
- School of Health Sciences, Central Michigan University, Mt. Pleasant, MI, USA.
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17
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Mangner N, Winzer EB, Linke A, Adams V. Locomotor and respiratory muscle abnormalities in HFrEF and HFpEF. Front Cardiovasc Med 2023; 10:1149065. [PMID: 37965088 PMCID: PMC10641491 DOI: 10.3389/fcvm.2023.1149065] [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: 01/20/2023] [Accepted: 10/02/2023] [Indexed: 11/16/2023] Open
Abstract
Heart failure (HF) is a chronic and progressive syndrome affecting worldwide billions of patients. Exercise intolerance and early fatigue are hallmarks of HF patients either with a reduced (HFrEF) or a preserved (HFpEF) ejection fraction. Alterations of the skeletal muscle contribute to exercise intolerance in HF. This review will provide a contemporary summary of the clinical and molecular alterations currently known to occur in the skeletal muscles of both HFrEF and HFpEF, and thereby differentiate the effects on locomotor and respiratory muscles, in particular the diaphragm. Moreover, current and future therapeutic options to address skeletal muscle weakness will be discussed focusing mainly on the effects of exercise training.
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Affiliation(s)
- Norman Mangner
- Department of Internal Medicine and Cardiology, Heart Center Dresden, Technische Universität Dresden, Dresden, Germany
| | - Ephraim B. Winzer
- Department of Internal Medicine and Cardiology, Heart Center Dresden, Technische Universität Dresden, Dresden, Germany
| | - Axel Linke
- Department of Internal Medicine and Cardiology, Heart Center Dresden, Technische Universität Dresden, Dresden, Germany
| | - Volker Adams
- Laboratory of Molecular and Experimental Cardiology, Heart Center Dresden, Technische Universität Dresden, Dresden, Germany
- Dresden Cardiovascular Research Institute and Core Laboratories GmbH, Dresden, Germany
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18
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Brochhagen J, Coll Barroso MT, Baumgart C, Wasmus DT, Freiwald J, Hoppe MW. Age, sex, endurance capacity, and chronic heart failure affect central and peripheral factors of oxygen uptake measured by non-invasive and continuous technologies: support of pioneer work using invasive or non-continuous measures. Front Sports Act Living 2023; 5:1218948. [PMID: 37731479 PMCID: PMC10507902 DOI: 10.3389/fspor.2023.1218948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Accepted: 08/21/2023] [Indexed: 09/22/2023] Open
Abstract
Introduction It is known that maximum oxygen uptake depends on age, sex, endurance capacity, and chronic heart failure. However, due to the required invasive or often applied non-continuous approaches, less is known on underlying central and peripheral factors. Thus, this study aimed to investigate the effects of age, sex, endurance capacity, and chronic heart failure on non-invasively and continuously measured central and peripheral factors of oxygen uptake. Methods 15 male children (11 ± 1 years), 15 male (24 ± 3 years) and 14 female recreationally active adults (23 ± 2 years), 12 male highly trained endurance athletes (24 ± 3 years), and 10 male elders (59 ± 6 years) and 10 chronic heart failure patients (62 ± 7 years) were tested during a cardiopulmonary exercise test on a cycling ergometer until exhaustion for: blood pressure, heart rate, stroke volume, cardiac output, cardiac power output, vastus lateralis muscle oxygen saturation, and (calculated) arterio-venous oxygen difference. For the non-invasive and continuous measurement of stroke volume and muscle oxygen saturation, bioreactance analysis and near-infrared spectroscopy were used, respectively. A two-factor repeated measure ANOVA and partial eta-squared effect sizes (η p 2 ) were applied for statistical analyses at rest, 80, and 100% of oxygen uptake. Results For the age effect, there were statistically significant group differences for all factors (p ≤ .033; η p 2 ≥ .169 ). Concerning sex, there were group differences for all factors (p ≤ .010; η p 2 ≥ .223 ), except diastolic blood pressure and heart rate (p ≥ .698; η p 2 ≤ .006 ). For the effect of endurance capacity, there were no group differences for any of the factors (p ≥ .065; η p 2 ≤ .129 ). Regarding chronic heart failure, there were group differences for the heart rate and arterio-venous oxygen difference (p ≤ .037; η p 2 ≥ .220 ). Discussion Age, sex, endurance capacity, and chronic heart failure affect central and peripheral factors of oxygen uptake measured by non-invasive and continuous technologies. Since most of our findings support pioneer work using invasive or non-continuous measures, the validity of our applied technologies is indirectly confirmed. Our outcomes allow direct comparison between different groups serving as reference data and framework for subsequent studies in sport science and medicine aiming to optimise diagnostics and interventions in athletes and patients.
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Affiliation(s)
- Joana Brochhagen
- Movement and Training Science, Faculty of Sport Science, Leipzig University, Leipzig, Germany
| | | | - Christian Baumgart
- Department of Movement and Training Science, Faculty of Humanities and Social Sciences, Institute of Sport Science, University of Wuppertal, Wuppertal, Germany
| | - Daniel T. Wasmus
- Movement and Training Science, Faculty of Sport Science, Leipzig University, Leipzig, Germany
| | - Jürgen Freiwald
- Department of Movement and Training Science, Faculty of Humanities and Social Sciences, Institute of Sport Science, University of Wuppertal, Wuppertal, Germany
| | - Matthias W. Hoppe
- Movement and Training Science, Faculty of Sport Science, Leipzig University, Leipzig, Germany
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19
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Sung HP, Hsu CY, Lee YH, Lin PL, Liao CT, Chung FP, Ko SL, Huang CY, Lin KC, Chang HY. Iron deficiency in Taiwanese patients with heart failure and reduced ejection fraction. J Chin Med Assoc 2023; 86:725-731. [PMID: 37314316 DOI: 10.1097/jcma.0000000000000949] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/15/2023] Open
Abstract
BACKGROUND Iron deficiency (ID) is a common comorbidity among patients with heart failure and reduced ejection fraction (HFrEF), and is associated with poorer outcomes independent of anemia. This study aimed to evaluate the prevalence and prognostic significance of ID in Taiwanese patients with HFrEF. METHODS We included HFrEF patients from two multicenter cohorts at different periods. The multivariate Cox regression analysis was applied to assess the risk of outcomes associated with ID, accounting for the varying risk of death. RESULTS Of the 3612 patients with HFrEF registered from 2013 to 2018, 665 patients (18.4%) had available baseline iron profile measurements. Of these, 290 patients (43.6%) were iron deficient; 20.2% had ID+/anemia+, 23.4% ID+/anemia-, 21.5% ID-/anemia+, and 34.9% ID-/anemia-. Regardless of anemia status, patients with coexisting ID had a higher risk than those without ID (all-cause mortality: 14.3 vs 9.5 per 100 patient-years, adjusted hazard ratio [HR] 1.33; 95% confidence interval [CI], 0.96-1.85; p = 0.091; cardiovascular mortality: 10.5 per 100 patient-years vs 6.1, adjusted HR 1.54 [95% CI, 1.03-2.30; p = 0.037]; cardiovascular mortality or first unplanned hospitalization for HF: 36.7 vs 19.7 per 100 patient-years, adjusted HR 1.57 [95% CI, 1.22-2.01; p < 0.001]). Among patients eligible for treatment in the IRONMAN trial design (43.9%), parenteral iron therapy was estimated to reduce heart failure hospitalizations and cardiovascular deaths by 13.7 per 100 patient-years. CONCLUSION Iron profiles were tested in less than one-fifth of the Taiwanese HFrEF cohort. ID was present in 43.6% of tested patients and was independently associated with poor prognosis in these patients.
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Affiliation(s)
- Hsiao-Ping Sung
- Heart Center, Cheng Hsin General Hospital, Taipei, Taiwan, ROC
- Institute of Hospital and Health Care Administration, Community Medicine Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Chien-Yi Hsu
- Division of Cardiology and Cardiovascular Research Center, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan, ROC
- Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC
- Taipei Heart Institute, Taipei Medical University, Taipei, Taiwan, ROC
| | - Ying-Hsiang Lee
- Department of Medicine, Mackay Medical College, New Taipei, Taiwan, ROC
- Cardiovascular Center, MacKay Memorial Hospital, Taipei, Taiwan, ROC
| | - Po-Lin Lin
- Department of Medicine, Mackay Medical College, New Taipei, Taiwan, ROC
- Division of Cardiology, Department of Internal Medicine, Hsinchu MacKay Memorial Hospital, Hsinchu, Taiwan, ROC
| | - Chia-Te Liao
- Division of Cardiology, Chi-Mei Medical Center, Tainan, Taiwan, ROC
| | - Fa-Po Chung
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Shao-Lun Ko
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Chun-Yao Huang
- Division of Cardiology and Cardiovascular Research Center, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan, ROC
- Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC
- Taipei Heart Institute, Taipei Medical University, Taipei, Taiwan, ROC
| | - Kuan-Chia Lin
- Institute of Hospital and Health Care Administration, Community Medicine Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Hung-Yu Chang
- Heart Center, Cheng Hsin General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
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20
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Zuo X, Li X, Tang K, Zhao R, Wu M, Wang Y, Li T. Sarcopenia and cardiovascular diseases: A systematic review and meta-analysis. J Cachexia Sarcopenia Muscle 2023; 14:1183-1198. [PMID: 37002802 PMCID: PMC10235887 DOI: 10.1002/jcsm.13221] [Citation(s) in RCA: 61] [Impact Index Per Article: 30.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Revised: 12/23/2022] [Accepted: 03/06/2023] [Indexed: 06/03/2023] Open
Abstract
Sarcopenia is an age-related disease and is often accompanied by other diseases. Now, many studies have shown that cardiovascular diseases (CVDs) may raise the incidence rate of sarcopenia. Therefore, the purpose of this study was to conduct a systematic review and meta-analysis to investigate the prevalence of sarcopenia in patients with CVDs compared with the general population, defined as relatively healthy non-hospitalized subjects. The databases of PubMed, Embase, Medline and Web of Science were searched for eligible studies published up to 12 November 2022. Two assessment tools were used to evaluate study quality and the risk of bias. Statistical analysis was conducted using STATA 14.0 and R Version 4.1.2. Thirty-eight out of the 89 629 articles retrieved were included in our review. The prevalence of sarcopenia ranged from 10.1% to 68.9% in patients with CVDs, and the pooled prevalence was 35% (95% confidence interval [95% CI]: 28-42%). The pooled prevalence of sarcopenia was 32% (95% CI: 23-41%) in patients with chronic heart failure (CHF), 61% (95% CI: 49-72%) in patients with acute decompensated heart failure (ADHF), 43% (95% CI: 2-85%) in patients with coronary artery disease, 30% (95% CI: 25-35%) in patients with cardiac arrhythmia (CA), 35% (95% CI: 10-59%) in patients with congenital heart disease and 12% (95% CI: 7-17%) in patients with unclassed CVDs. However, in the general population, the prevalence of sarcopenia varied from 2.9% to 28.6% and the pooled prevalence was 13% (95% CI: 9-17%), suggesting that the prevalence of sarcopenia in patients with CVDs was about twice compared with the general population. The prevalence of sarcopenia was significantly higher only in patients with ADHF, CHF and CA compared with the general population. There is a positive correlation between CVDs and sarcopenia. The prevalence of sarcopenia is higher in patients with CVDs than that in the general population. With global aging, sarcopenia has brought a heavy burden to individuals and society. Therefore, it is important to identify the populations with high-risk or probable sarcopenia in order to do an early intervention, such as exercise, to counteract or slow down the progress of sarcopenia.
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Affiliation(s)
- Xinrong Zuo
- Department of AnesthesiologyThe Affiliated Hospital of Southwest Medical UniversityLuzhouSichuanChina
| | - Xuehong Li
- Department of Anesthesiology, Laboratory of Mitochondria and Metabolism, National Clinical Research Center for GeriatricsWest China Hospital of Sichuan UniversityChengduSichuanChina
| | - Kuo Tang
- Department of Anesthesiology, Laboratory of Mitochondria and Metabolism, National Clinical Research Center for GeriatricsWest China Hospital of Sichuan UniversityChengduSichuanChina
| | - Rui Zhao
- Department of Anesthesiology, Laboratory of Mitochondria and Metabolism, National Clinical Research Center for GeriatricsWest China Hospital of Sichuan UniversityChengduSichuanChina
| | - Minming Wu
- Department of Anesthesiology, Laboratory of Mitochondria and Metabolism, National Clinical Research Center for GeriatricsWest China Hospital of Sichuan UniversityChengduSichuanChina
| | - Yang Wang
- Department of Anesthesiology, Laboratory of Mitochondria and Metabolism, National Clinical Research Center for GeriatricsWest China Hospital of Sichuan UniversityChengduSichuanChina
| | - Tao Li
- Department of AnesthesiologyThe Affiliated Hospital of Southwest Medical UniversityLuzhouSichuanChina
- Department of Anesthesiology, Laboratory of Mitochondria and Metabolism, National Clinical Research Center for GeriatricsWest China Hospital of Sichuan UniversityChengduSichuanChina
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21
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Malinowska-Borowska J, Piecuch M, Szlacheta P, Kulik A, Niedziela J, Nowak JU, Pyka Ł, Gąsior M, Rozentryt P. Prognostic Value of Spot Urinary Creatinine Concentration and Its Relationship with Body Composition Parameters in HF Patients. Biomedicines 2023; 11:biomedicines11051429. [PMID: 37239100 DOI: 10.3390/biomedicines11051429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2023] [Revised: 05/10/2023] [Accepted: 05/10/2023] [Indexed: 05/28/2023] Open
Abstract
BACKGROUND Low 24-h urinary excretion of creatinine in patients with heart failure (HF) is believed to reflect muscle wasting and is associated with a poor prognosis. Recently, spot urinary creatinine concentration (SUCR) has been suggested as a useful prognostic factor in selected HF cohorts. This more practical and cheaper approach has never been tested in an unselected HF population. Moreover, neither the relation between SUCR and body composition markers nor the association of SUCR with the markers of volume overload, which are known to worsen clinical outcome, has been studied so far. The aim of the study was to check the prognostic value of SUCR in HF patients after adjusting for body composition and indirect markers of volume overload. METHODS In 911 HF patients, morning SUCR was determined and body composition scanning using dual X-ray absorptiometry (DEXA) was performed. Univariable and multivariable predictors of log SUCR were analyzed. All participants were divided into quartiles of SUCR. RESULTS In univariable analysis, SUCR weakly correlated with fat-free mass (R = 0.09, p = 0.01). Stronger correlations were shown between SUCR and loop diuretic dose (R = 0.16, p < 0.0001), NTproBNP (R = -0.15, p < 0.0001) and serum sodium (R = 0.16, p < 0.0001). During 3 years of follow-up, 353 (38.7%) patients died. Patients with lower SUCR were more frequently female, and their functional status was worse. The lowest mortality was observed in the top quartile of SUCR. In the unadjusted Cox regression analysis, the relative risk of death in all three lower quartiles of SUCR was higher by roughly 80% compared to the top SUCR quartile. Apart from lower SUCR, the significant predictors of death were age and malnutrition but not body composition. After adjustment for loop diuretic dose and percent of recommended dose of mineralocorticoid receptor antagonists, the difference in mortality vanished completely. CONCLUSIONS Lower SUCR levels in HF patients are associated with a worse outcome, but this effect is not correlated with fat-free mass. Fluid overload-driven effects may link lower SUCR with higher mortality in HF.
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Affiliation(s)
- Jolanta Malinowska-Borowska
- Department of Chronic Diseases and Civilization-Related Hazards, Faculty of Public Health in Bytom, Medical University of Silesia in Katowice, 41-902 Bytom, Poland
| | - Małgorzata Piecuch
- Department of Chronic Diseases and Civilization-Related Hazards, Faculty of Public Health in Bytom, Medical University of Silesia in Katowice, 41-902 Bytom, Poland
| | - Patryk Szlacheta
- Department of Chronic Diseases and Civilization-Related Hazards, Faculty of Public Health in Bytom, Medical University of Silesia in Katowice, 41-902 Bytom, Poland
| | - Aleksandra Kulik
- Department of Chronic Diseases and Civilization-Related Hazards, Faculty of Public Health in Bytom, Medical University of Silesia in Katowice, 41-902 Bytom, Poland
| | - Jacek Niedziela
- Department of Cardiology, Faculty of Medical Sciences in Zabrze, Silesian Centre for Heart Disease, Medical University of Silesia, 41-800 Zabrze, Poland
| | - Jolanta Urszula Nowak
- Department of Cardiology, Faculty of Medical Sciences in Zabrze, Silesian Centre for Heart Disease, Medical University of Silesia, 41-800 Zabrze, Poland
| | - Łukasz Pyka
- Department of Cardiology, Faculty of Medical Sciences in Zabrze, Silesian Centre for Heart Disease, Medical University of Silesia, 41-800 Zabrze, Poland
| | - Mariusz Gąsior
- Department of Cardiology, Faculty of Medical Sciences in Zabrze, Silesian Centre for Heart Disease, Medical University of Silesia, 41-800 Zabrze, Poland
| | - Piotr Rozentryt
- Department of Chronic Diseases and Civilization-Related Hazards, Faculty of Public Health in Bytom, Medical University of Silesia in Katowice, 41-902 Bytom, Poland
- Department of Cardiology, Faculty of Medical Sciences in Zabrze, Silesian Centre for Heart Disease, Medical University of Silesia, 41-800 Zabrze, Poland
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22
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Mendelson AA, Erickson D, Villar R. The role of the microcirculation and integrative cardiovascular physiology in the pathogenesis of ICU-acquired weakness. Front Physiol 2023; 14:1170429. [PMID: 37234410 PMCID: PMC10206327 DOI: 10.3389/fphys.2023.1170429] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Accepted: 04/28/2023] [Indexed: 05/28/2023] Open
Abstract
Skeletal muscle dysfunction after critical illness, defined as ICU-acquired weakness (ICU-AW), is a complex and multifactorial syndrome that contributes significantly to long-term morbidity and reduced quality of life for ICU survivors and caregivers. Historically, research in this field has focused on pathological changes within the muscle itself, without much consideration for their in vivo physiological environment. Skeletal muscle has the widest range of oxygen metabolism of any organ, and regulation of oxygen supply with tissue demand is a fundamental requirement for locomotion and muscle function. During exercise, this process is exquisitely controlled and coordinated by the cardiovascular, respiratory, and autonomic systems, and also within the skeletal muscle microcirculation and mitochondria as the terminal site of oxygen exchange and utilization. This review highlights the potential contribution of the microcirculation and integrative cardiovascular physiology to the pathogenesis of ICU-AW. An overview of skeletal muscle microvascular structure and function is provided, as well as our understanding of microvascular dysfunction during the acute phase of critical illness; whether microvascular dysfunction persists after ICU discharge is currently not known. Molecular mechanisms that regulate crosstalk between endothelial cells and myocytes are discussed, including the role of the microcirculation in skeletal muscle atrophy, oxidative stress, and satellite cell biology. The concept of integrated control of oxygen delivery and utilization during exercise is introduced, with evidence of physiological dysfunction throughout the oxygen delivery pathway - from mouth to mitochondria - causing reduced exercise capacity in patients with chronic disease (e.g., heart failure, COPD). We suggest that objective and perceived weakness after critical illness represents a physiological failure of oxygen supply-demand matching - both globally throughout the body and locally within skeletal muscle. Lastly, we highlight the value of standardized cardiopulmonary exercise testing protocols for evaluating fitness in ICU survivors, and the application of near-infrared spectroscopy for directly measuring skeletal muscle oxygenation, representing potential advancements in ICU-AW research and rehabilitation.
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Affiliation(s)
- Asher A. Mendelson
- Section of Critical Care Medicine, Department of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
| | - Dustin Erickson
- Section of Critical Care Medicine, Department of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
| | - Rodrigo Villar
- Faculty of Kinesiology and Recreation Management, University of Manitoba, Winnipeg, MB, Canada
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23
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Aitken CR, Stewart GM, Walsh JR, Palmer T, Adams L, Sabapathy S, Morris NR. Exertional dyspnea responses to the Dyspnea Challenge in heart failure: Comparison to chronic obstructive pulmonary disease. Heart Lung 2023; 58:108-115. [PMID: 36455422 DOI: 10.1016/j.hrtlng.2022.11.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 11/07/2022] [Accepted: 11/20/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND In heart failure (HF), exertional dyspnea is a common symptom, but validated field-based tests for its measurement are limited. The Dyspnea Challenge is a two-minute uphill treadmill walk designed to measure exertional dyspnea in cardiopulmonary disease. OBJECTIVES The purpose of this study was to establish the test-retest reliability of the Dyspnea Challenge in HF and to compare the exercise responses to a group with chronic obstructive pulmonary disease (COPD). METHODS The study was an experimental, single-blind, randomized, multi-site project that recruited individuals with HF (New York Heart Association I-III) and COPD (Global Initiative for Chronic Obstructive Lung Disease II-IV). Participants completed two visits. On the first visit, participants performed two six-minute walk tests (6MWT), followed by two to three Dyspnea Challenges to calculate treadmill speed and gradient. At Visit Two, participants performed two separate Dyspnea Challenges, with one including measures of pulmonary gas exchange and central hemodynamics. RESULTS Twenty-one individuals with HF (10 female; 66±11years; ejection fraction:45.3 ± 6.1%; six-minute distance(6MWD) 520 ± 97 m), and 25 COPD (11 female; 68 ± 10 yr; forced expiratory volume in 1 s:47.6 ± 11.5%; 6MWD: 430 ± 101 m). Intraclass correlation coefficients demonstrated excellent test-retest reliability for HF (0.94, P<.01) and COPD (0.95, P<.01). While achieving similar end-exercise exertional dyspnea intensities (P=.60), the HF group walked at a higher average speed (4.2 ± 0.8 vs. 3.5 ± 0.8km·h-1) and gradient (10.3 ± 2.8 vs. 9.6 ± 2.8%) and a greater oxygen uptake (P<.01) and ventilation (P<.01) than those with COPD. While achieving similar cardiac outputs (P=.98), stroke volumes (P=.97), and heart rates (P=.83), those with HF displayed a larger arteriovenous oxygen difference (P<.01), while those with COPD exhibited greater decreases in inspiratory capacity (P=.03), arterial oxygen saturation (P=.02), and breathing reserve (P<.01). CONCLUSIONS The Dyspnea Challenge is a reliable test-retest measure of exertional dyspnea in HF. Typical to their pathologies, HF seemed limited by an inadequate modulation of cardiac output, while ventilatory constraints hampered those with COPD.
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Affiliation(s)
- Craig R Aitken
- School of Health Sciences and Social Work, Southport, QLD. Australia; Allied Health Research Collaborative. The Prince Charles Hospital. Brisbane. QLD. Australia; Heart Lung Institute. The Prince Charles Hospital Brisbane. QLD. Australia.
| | - Glenn M Stewart
- School of Health Sciences and Social Work, Southport, QLD. Australia; Allied Health Research Collaborative. The Prince Charles Hospital. Brisbane. QLD. Australia; Heart Lung Institute. The Prince Charles Hospital Brisbane. QLD. Australia; Menzies Health Institute of Queensland, Griffith University, Southport, QLD. Australia
| | - James R Walsh
- School of Health Sciences and Social Work, Southport, QLD. Australia; Allied Health Research Collaborative. The Prince Charles Hospital. Brisbane. QLD. Australia; Heart Lung Institute. The Prince Charles Hospital Brisbane. QLD. Australia
| | - Tanya Palmer
- School of Health Sciences and Social Work, Southport, QLD. Australia
| | - Lewis Adams
- School of Health Sciences and Social Work, Southport, QLD. Australia
| | - Surendran Sabapathy
- School of Health Sciences and Social Work, Southport, QLD. Australia; Menzies Health Institute of Queensland, Griffith University, Southport, QLD. Australia
| | - Norman R Morris
- School of Health Sciences and Social Work, Southport, QLD. Australia; Allied Health Research Collaborative. The Prince Charles Hospital. Brisbane. QLD. Australia; Heart Lung Institute. The Prince Charles Hospital Brisbane. QLD. Australia; Menzies Health Institute of Queensland, Griffith University, Southport, QLD. Australia
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24
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Jun L, Robinson M, Geetha T, Broderick TL, Babu JR. Prevalence and Mechanisms of Skeletal Muscle Atrophy in Metabolic Conditions. Int J Mol Sci 2023; 24:ijms24032973. [PMID: 36769296 PMCID: PMC9917738 DOI: 10.3390/ijms24032973] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 01/29/2023] [Accepted: 01/30/2023] [Indexed: 02/05/2023] Open
Abstract
Skeletal muscle atrophy is prevalent in a myriad of pathological conditions, such as diabetes, denervation, long-term immobility, malnutrition, sarcopenia, obesity, Alzheimer's disease, and cachexia. This is a critically important topic that has significance in the health of the current society, particularly older adults. The most damaging effect of muscle atrophy is the decreased quality of life from functional disability, increased risk of fractures, decreased basal metabolic rate, and reduced bone mineral density. Most skeletal muscle in humans contains slow oxidative, fast oxidative, and fast glycolytic muscle fiber types. Depending on the pathological condition, either oxidative or glycolytic muscle type may be affected to a greater extent. This review article discusses the prevalence of skeletal muscle atrophy and several mechanisms, with an emphasis on high-fat, high-sugar diet patterns, obesity, and diabetes, but including other conditions such as sarcopenia, Alzheimer's disease, cancer cachexia, and heart failure.
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Affiliation(s)
- Lauren Jun
- Department of Nutritional Sciences, Auburn University, Auburn, AL 36849, USA
| | - Megan Robinson
- Department of Nutritional Sciences, Auburn University, Auburn, AL 36849, USA
| | - Thangiah Geetha
- Department of Nutritional Sciences, Auburn University, Auburn, AL 36849, USA
- Boshell Metabolic Diseases and Diabetes Program, Auburn University, Auburn, AL 36849, USA
| | - Tom L. Broderick
- Department of Physiology, Laboratory of Diabetes and Exercise Metabolism, College of Graduate Studies, Midwestern University, Glendale, AZ 85308, USA
| | - Jeganathan Ramesh Babu
- Department of Nutritional Sciences, Auburn University, Auburn, AL 36849, USA
- Boshell Metabolic Diseases and Diabetes Program, Auburn University, Auburn, AL 36849, USA
- Correspondence: ; Tel.: +1-223-844-3840
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25
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Heart Failure and Frailty Have Synergistic Negative Effects on Skeletal Muscle Mass and Upper and Lower Limb Muscle Strength. TOPICS IN GERIATRIC REHABILITATION 2023. [DOI: 10.1097/tgr.0000000000000387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
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Umehara T, Kaneguchi A, Yamasaki T, Katayama N, Kawakami W, Kuwahara D, Kito N. Reduced upper and lower limb muscle strengths without reduced skeletal muscle in elderly patients with heart failure. J Rural Med 2023; 18:8-14. [PMID: 36700128 PMCID: PMC9832311 DOI: 10.2185/jrm.2022-029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Accepted: 08/02/2022] [Indexed: 01/06/2023] Open
Abstract
Objective: This study aimed to characterize the muscle strength and skeletal muscle mass of patients with heart failure by investigating hand-grip strength, five times sit-to-stand (5STS) results, and skeletal muscle mass index (SMI). Materials and Methods: Muscle strength was assessed based on hand-grip strength and 5STS, while skeletal muscle mass was assessed using a bioelectrical impedance analyzer. Hierarchical logistic regression analysis was performed to explore the association between patients with heart failure and healthy elderly individuals. Results: Hierarchical logistic regression analysis was performed to examine the muscle strength and skeletal muscle mass characteristics in patients with heart failure. Hand-grip strength and 5STS responses but not SMI outcomes differed significantly between the two groups. The results of the hierarchical logistic regression analysis revealed that the hand-grip strength and 5STS were significant predictors of heart failure. The odds ratios for hand-grip strength and 5STS were 1.44 and 0.53, respectively. Conclusion: Our results suggested that upper and lower limb muscle strengths (handgrip strength and 5STS) in elderly patients with heart failure worsened significantly without a decrease in skeletal muscle mass.
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Affiliation(s)
- Takuya Umehara
- Department of Rehabilitation, Faculty of Rehabilitation,
Hiroshima International University, Japan
| | - Akinori Kaneguchi
- Department of Rehabilitation, Faculty of Rehabilitation,
Hiroshima International University, Japan
| | - Takahiro Yamasaki
- Department of Rehabilitation, Faculty of Rehabilitation,
Hiroshima International University, Japan
| | | | | | | | - Nobuhiro Kito
- Department of Rehabilitation, Faculty of Rehabilitation,
Hiroshima International University, Japan
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27
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Kadowaki T, Maegawa H, Watada H, Yabe D, Node K, Murohara T, Wada J. Interconnection between cardiovascular, renal and metabolic disorders: A narrative review with a focus on Japan. Diabetes Obes Metab 2022; 24:2283-2296. [PMID: 35929483 PMCID: PMC9804928 DOI: 10.1111/dom.14829] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 07/18/2022] [Accepted: 08/01/2022] [Indexed: 01/07/2023]
Abstract
Insights from epidemiological, clinical and basic research are illuminating the interplay between metabolic disorders, cardiovascular disease (CVD) and kidney dysfunction, termed cardio-renal-metabolic (CRM) disease. Broadly defined, CRM disease involves multidirectional interactions between metabolic diseases such as type 2 diabetes (T2D), various types of CVD and chronic kidney disease (CKD). T2D confers increased risk for heart failure, which-although well known-has only recently come into focus for treatment, and may differ by ethnicity, whereas atherosclerotic heart disease is a well-established complication of T2D. Many people with T2D also have CKD, with a higher risk in Asians than their Western counterparts. Furthermore, CVD increases the risk of CKD and vice versa, with heart failure, notably, present in approximately half of CKD patients. Molecular mechanisms involved in CRM disease include hyperglycaemia, insulin resistance, hyperactivity of the renin-angiotensin-aldosterone system, production of advanced glycation end-products, oxidative stress, lipotoxicity, endoplasmic reticulum stress, calcium-handling abnormalities, mitochondrial malfunction and deficient energy production, and chronic inflammation. Pathophysiological manifestations of these processes include diabetic cardiomyopathy, vascular endothelial dysfunction, cardiac and renal fibrosis, glomerular hyperfiltration, renal hypoperfusion and venous congestion, reduced exercise tolerance leading to metabolic dysfunction, and calcification of atherosclerotic plaque. Importantly, recognition of the interaction between CRM diseases would enable a more holistic approach to CRM care, rather than isolated treatment of individual conditions, which may improve patient outcomes. Finally, aspects of CRM diseases may differ between Western and East Asian countries such as Japan, a super-ageing country, with potential differences in epidemiology, complications and prognosis that represent an important avenue for future research.
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Affiliation(s)
| | | | - Hirotaka Watada
- Department of Metabolism and EndocrinologyJuntendo UniversityTokyoJapan
| | - Daisuke Yabe
- Department of Diabetes, Endocrinology and Metabolism and Department of Rheumatology and Clinical ImmunologyGifu University Graduate School of MedicineGifuJapan
- Yutaka Seino Distinguished Center for Diabetes ResearchKansai Electric Power Medical Research InstituteKyotoJapan
- Preemptive Food Research CenterGifu University Institute for Advanced StudyGifuJapan
- Center for Healthcare Information TechnologyTokai National Higher Education and Research SystemNagoyaJapan
| | - Koichi Node
- Department of Cardiovascular MedicineSaga UniversitySagaJapan
| | | | - Jun Wada
- Department of Nephrology, Rheumatology, Endocrinology and MetabolismOkayama UniversityOkayamaJapan
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28
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Skeletal muscle mitochondrial remodeling in heart failure: An update on mechanisms and therapeutic opportunities. Biomed Pharmacother 2022; 155:113833. [DOI: 10.1016/j.biopha.2022.113833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Revised: 10/04/2022] [Accepted: 10/06/2022] [Indexed: 11/22/2022] Open
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Hiraiwa H, Okumura T, Murohara T. Amino acid profiling to predict prognosis in patients with heart failure: an expert review. ESC Heart Fail 2022; 10:32-43. [PMID: 36300549 PMCID: PMC9871678 DOI: 10.1002/ehf2.14222] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 10/05/2022] [Accepted: 10/14/2022] [Indexed: 01/27/2023] Open
Abstract
Heart failure is a complex disease with a poor prognosis. A number of widely used prognostic tools have limitations, so efforts to identify novel predictive markers and measures are important. As a metabolomics tool, amino acid profiling has shown promise in predicting heart failure prognosis; however, the evidence has not yet been sufficiently evaluated. We describe the utilization of amino acids in the healthy heart and in heart failure before reviewing the literature on amino acid profiling for prognostic prediction. We expertly interpret the findings and provide suggestions for future research to advance the understanding of the prognostic potential of amino acid profiling in heart failure. Our analysis revealed correlations between amino acid biomarkers and traditional prognostic factors, the additional prognostic value of amino acid biomarkers over traditional prognostic factors, and the successful use of amino acid biomarkers to distinguish heart failure aetiology. Although certain amino acid biomarkers have demonstrated additional prognostic value over traditional measures, such as New York Heart Association functional class, these measures are deeply rooted in clinical practice; thus, amino acid biomarkers may be best placed as additional prognostic tools to improve current risk stratification rather than as surrogate tools. Once the metabolic profiles of different heart failure aetiologies have been clearly delineated, the amino acid biomarkers with the most value in prognostic prediction should be determined. Amino acid profiling could be useful to evaluate the pathophysiology and metabolic status of different heart failure cohorts, distinguish heart failure aetiologies, and improve risk stratification and prognostic prediction.
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Affiliation(s)
- Hiroaki Hiraiwa
- Department of CardiologyNagoya University Graduate School of MedicineNagoyaJapan
| | - Takahiro Okumura
- Department of CardiologyNagoya University Graduate School of MedicineNagoyaJapan
| | - Toyoaki Murohara
- Department of CardiologyNagoya University Graduate School of MedicineNagoyaJapan
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The Acute-Phase Ambulation Program Improves Clinical Outcome for Acute Heart Failure. J Cardiovasc Dev Dis 2022; 9:jcdd9100314. [PMID: 36286266 PMCID: PMC9604221 DOI: 10.3390/jcdd9100314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Revised: 09/18/2022] [Accepted: 09/18/2022] [Indexed: 11/17/2022] Open
Abstract
It remains unclear whether the acute-phase ambulation program (AAP) improves the prognosis of heart failure (HF) patients. We examined the association between the initiation of AAP and the prognosis of patients with worsening HF. We enrolled 560 consecutive patients admitted due to worsening HF from March 2019 to April 2021. Our hospital introduced AAP in May 2020, but we did not perform AAP until April 2020. We retrospectively compared cardiac events within 180 days after discharge between patients admitted before April 2020 (conventional group) and after May 2020 (AAP group). Primary endpoints were all-cause mortality and readmission for worsening HF. The Kaplan–Meier survival curves showed a significantly lower event rate in the AAP group in HF readmission or the primary endpoint (p = 0.020 and p = 0.014). The occurrence of the primary endpoint was associated with age, history of HF, systolic blood pressure, medications including renin–angiotensin system inhibitors or angiotensin receptor blocker, hemoglobin, NT-proBNP, and AAP participation. After adjusting for these parameters and sex, participation in AAP was an independent factor associated with a reduced risk of primary endpoint occurrence (hazard ratio of 0.62 (0.41–0.95), p = 0.028). The AAP for patients with acute HF might lead to improved short-term prognosis and should be considered for implementation.
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Kulej-Lyko K, Niewinski P, Tubek S, Krawczyk M, Kosmala W, Ponikowski P. Inhibition of peripheral chemoreceptors improves ventilatory efficiency during exercise in heart failure with preserved ejection fraction − a role of tonic activity and acute reflex response. Front Physiol 2022; 13:911636. [PMID: 36111161 PMCID: PMC9470150 DOI: 10.3389/fphys.2022.911636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Accepted: 07/19/2022] [Indexed: 11/22/2022] Open
Abstract
Peripheral chemoreceptors (PChRs) play a significant role in maintaining adequate oxygenation in the bloodstream. PChRs functionality comprises two components: tonic activity (PChT) which regulates ventilation during normoxia and acute reflex response (peripheral chemosensitivity, PChS), which increases ventilation following a specific stimulus. There is a clear link between augmented PChS and exercise intolerance in patients with heart failure with reduced ejection fraction. It has been also shown that inhibition of PChRs leads to the improvement in exercise capacity. However, it has not been established yet: 1) whether similar mechanisms take part in heart failure with preserved ejection fraction (HFpEF) and 2) which component of PChRs functionality (PChT vs. PChS) is responsible for the benefit seen after the acute experimental blockade. To answer those questions we enrolled 12 stable patients with HFpEF. All participants underwent an assessment of PChT (attenuation of minute ventilation in response to low-dose dopamine infusion), PChS (enhancement of minute ventilation in response to hypoxia) and a symptom-limited cardiopulmonary exercise test on cycle ergometer. All tests were placebo-controlled, double-blinded and performed in a randomized order. Under resting conditions and at normoxia dopamine attenuated minute ventilation and systemic vascular resistance (p = 0.03 for both). These changes were not seen with placebo. Dopamine also decreased ventilatory and mean arterial pressure responses to hypoxia (p < 0.05 for both). Inhibition of PChRs led to a decrease in V˙E/V˙CO2 comparing to placebo (36 ± 3.6 vs. 34.3 ± 3.7, p = 0.04), with no effect on peak oxygen consumption. We found a significant relationship between PChT and the relative decrement of V˙E/V˙CO2 on dopamine comparing to placebo (R = 0.76, p = 0.005). There was a trend for correlation between PChS (on placebo) and V˙E/V˙CO2 during placebo infusion (R = 0.56, p = 0.059), but the relative improvement in V˙E/V˙CO2 was not related to the change in PChS (dopamine vs. placebo). We did not find a significant relationship between PChT and PChS. In conclusion, inhibition of PChRs in HFpEF population improves ventilatory efficiency during exercise. Increased PChS is associated with worse (higher) V˙E/V˙CO2, whereas PChT predicts an improvement in V˙E/V˙CO2 after PChRs inhibition. This results may be meaningful for patient selection in further clinical trials involving PChRs modulation.
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Affiliation(s)
- Katarzyna Kulej-Lyko
- Institute of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland
- Department of Cardiology, University Clinical Hospital, Wroclaw, Poland
- *Correspondence: Katarzyna Kulej-Lyko,
| | - Piotr Niewinski
- Institute of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland
- Department of Cardiology, University Clinical Hospital, Wroclaw, Poland
| | - Stanislaw Tubek
- Institute of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland
- Department of Cardiology, University Clinical Hospital, Wroclaw, Poland
| | | | - Wojciech Kosmala
- Institute of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland
- Department of Cardiology, University Clinical Hospital, Wroclaw, Poland
| | - Piotr Ponikowski
- Institute of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland
- Department of Cardiology, University Clinical Hospital, Wroclaw, Poland
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Voorrips SN, Saucedo-Orozco H, Sánchez-Aguilera PI, De Boer RA, Van der Meer P, Westenbrink BD. Could SGLT2 Inhibitors Improve Exercise Intolerance in Chronic Heart Failure? Int J Mol Sci 2022; 23:8631. [PMID: 35955784 PMCID: PMC9369142 DOI: 10.3390/ijms23158631] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 07/28/2022] [Accepted: 07/29/2022] [Indexed: 12/04/2022] Open
Abstract
Despite the constant improvement of therapeutical options, heart failure (HF) remains associated with high mortality and morbidity. While new developments in guideline-recommended therapies can prolong survival and postpone HF hospitalizations, impaired exercise capacity remains one of the most debilitating symptoms of HF. Exercise intolerance in HF is multifactorial in origin, as the underlying cardiovascular pathology and reactive changes in skeletal muscle composition and metabolism both contribute. Recently, sodium-related glucose transporter 2 (SGLT2) inhibitors were found to improve cardiovascular outcomes significantly. Whilst much effort has been devoted to untangling the mechanisms responsible for these cardiovascular benefits of SGLT2 inhibitors, little is known about the effect of SGLT2 inhibitors on exercise performance in HF. This review provides an overview of the pathophysiological mechanisms that are responsible for exercise intolerance in HF, elaborates on the potential SGLT2-inhibitor-mediated effects on these phenomena, and provides an up-to-date overview of existing studies on the effect of SGLT2 inhibitors on clinical outcome parameters that are relevant to the assessment of exercise capacity. Finally, current gaps in the evidence and potential future perspectives on the effects of SGLT2 inhibitors on exercise intolerance in chronic HF are discussed.
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Affiliation(s)
- Suzanne N. Voorrips
- Department of Cardiology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands; (H.S.-O.); (P.I.S.-A.); (R.A.D.B.); (P.V.d.M.)
| | | | | | | | | | - B. Daan Westenbrink
- Department of Cardiology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands; (H.S.-O.); (P.I.S.-A.); (R.A.D.B.); (P.V.d.M.)
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Rao P, Belanger MJ, Robbins JM. Exercise, Physical Activity, and Cardiometabolic Health: Insights into the Prevention and Treatment of Cardiometabolic Diseases. Cardiol Rev 2022; 30:167-178. [PMID: 34560712 PMCID: PMC8920940 DOI: 10.1097/crd.0000000000000416] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Physical activity (PA) and exercise are widely recognized as essential components of primary and secondary cardiovascular disease (CVD) prevention efforts and are emphasized in the health promotion guidelines of numerous professional societies and committees. The protean benefits of PA and exercise extend across the spectrum of CVD, and include the improvement and reduction of risk factors and events for atherosclerotic CVD (ASCVD), cardiometabolic disease, heart failure, and atrial fibrillation (AF), respectively. Here, we highlight recent insights into the salutary effects of PA and exercise on the primary and secondary prevention of ASCVD, including their beneficial effects on both traditional and nontraditional risk mediators; exercise "prescriptions" for ASCVD; the role of PA regular exercise in the prevention and treatment of heart failure; and the relationships between, PA, exercise, and AF. While our understanding of the relationship between exercise and CVD has evolved considerably, several key questions remain including the association between extreme volumes of exercise and subclinical ASCVD and its risk; high-intensity exercise and resistance (strength) training as complementary modalities to continuous aerobic exercise; and dose- and intensity-dependent associations between exercise and AF. Recent advances in molecular profiling technologies (ie, genomics, transcriptomics, proteomics, and metabolomics) have begun to shed light on interindividual variation in cardiometabolic responses to PA and exercise and may provide new opportunities for clinical prediction in addition to mechanistic insights.
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Affiliation(s)
- Prashant Rao
- Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA
- Cardiovascular Research Center, Beth Israel Deaconess Medical Center, Boston, MA
| | | | - Jeremy M. Robbins
- Cardiovascular Research Center, Beth Israel Deaconess Medical Center, Boston, MA
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA
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Nyberg M, Jones AM. Matching of O2 Utilization and O2 Delivery in Contracting Skeletal Muscle in Health, Aging, and Heart Failure. Front Physiol 2022; 13:898395. [PMID: 35774284 PMCID: PMC9237395 DOI: 10.3389/fphys.2022.898395] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Accepted: 05/05/2022] [Indexed: 12/12/2022] Open
Abstract
Skeletal muscle is one of the most dynamic metabolic organs as evidenced by increases in metabolic rate of >150-fold from rest to maximal contractile activity. Because of limited intracellular stores of ATP, activation of metabolic pathways is required to maintain the necessary rates of ATP re-synthesis during sustained contractions. During the very early phase, phosphocreatine hydrolysis and anaerobic glycolysis prevails but as activity extends beyond ∼1 min, oxidative phosphorylation becomes the major ATP-generating pathway. Oxidative metabolism of macronutrients is highly dependent on the cardiovascular system to deliver O2 to the contracting muscle fibres, which is ensured through a tight coupling between skeletal muscle O2 utilization and O2 delivery. However, to what extent O2 delivery is ideal in terms of enabling optimal metabolic and contractile function is context-dependent and determined by a complex interaction of several regulatory systems. The first part of the review focuses on local and systemic mechanisms involved in the regulation of O2 delivery and how integration of these influences the matching of skeletal muscle O2 demand and O2 delivery. In the second part, alterations in cardiovascular function and structure associated with aging and heart failure, and how these impact metabolic and contractile function, will be addressed. Where applicable, the potential of exercise training to offset/reverse age- and disease-related cardiovascular declines will be highlighted in the context of skeletal muscle metabolic function. The review focuses on human data but also covers animal observations.
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Affiliation(s)
- Michael Nyberg
- Vascular Biology, Global Drug Discovery, Novo Nordisk A/S, Maaloev, Denmark
- *Correspondence: Michael Nyberg,
| | - Andrew M. Jones
- Department of Sport and Health Sciences, University of Exeter, Exeter, United Kingdom
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35
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Park LK, Coggan AR, Peterson LR. Skeletal Muscle Contractile Function in Heart Failure With Reduced Ejection Fraction-A Focus on Nitric Oxide. Front Physiol 2022; 13:872719. [PMID: 35721565 PMCID: PMC9198547 DOI: 10.3389/fphys.2022.872719] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Accepted: 05/09/2022] [Indexed: 11/17/2022] Open
Abstract
Despite advances over the past few decades, heart failure with reduced ejection fraction (HFrEF) remains not only a mortal but a disabling disease. Indeed, the New York Heart Association classification of HFrEF severity is based on how much exercise a patient can perform. Moreover, exercise capacity-both aerobic exercise performance and muscle power-are intimately linked with survival in patients with HFrEF. This review will highlight the pathologic changes in skeletal muscle in HFrEF that are related to impaired exercise performance. Next, it will discuss the key role that impaired nitric oxide (NO) bioavailability plays in HFrEF skeletal muscle pathology. Lastly, it will discuss intriguing new data suggesting that the inorganic nitrate 'enterosalivary pathway' may be leveraged to increase NO bioavailability via ingestion of inorganic nitrate. This ingestion of inorganic nitrate has several advantages over organic nitrate (e.g., nitroglycerin) and the endogenous nitric oxide synthase pathway. Moreover, inorganic nitrate has been shown to improve exercise performance: both muscle power and aerobic capacity, in some recent small but well-controlled, cross-over studies in patients with HFrEF. Given the critical importance of better exercise performance for the amelioration of disability as well as its links with improved outcomes in patients with HFrEF, further studies of inorganic nitrate as a potential novel treatment is critical.
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Affiliation(s)
- Lauren K. Park
- Department of Medicine, Cardiology Division, Washington University School of Medicine, Saint Louis, MO, United States
| | - Andrew R. Coggan
- Department of Kinesiology, Indiana University Purdue University, Indianapolis, IN, United States
| | - Linda R. Peterson
- Department of Medicine, Cardiology Division, Washington University School of Medicine, Saint Louis, MO, United States
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36
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Blanquet M, Massoulié G, Boirie Y, Guiguet-Auclair C, Mulliez A, Anker S, Boiteux MCD, Jean F, Combaret N, Souteyrand G, Riocreux C, Pereira B, Motreff P, Rossignol P, Clerfond G, Eschalier R. Handgrip strength to screen early-onset sarcopenia in heart failure. Clin Nutr ESPEN 2022; 50:183-190. [DOI: 10.1016/j.clnesp.2022.05.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 05/09/2022] [Accepted: 05/26/2022] [Indexed: 11/16/2022]
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Kulej-Lyko K, Niewinski P, Tubek S, Ponikowski P. Contribution of Peripheral Chemoreceptors to Exercise Intolerance in Heart Failure. Front Physiol 2022; 13:878363. [PMID: 35492596 PMCID: PMC9046845 DOI: 10.3389/fphys.2022.878363] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 03/29/2022] [Indexed: 01/08/2023] Open
Abstract
Peripheral chemoreceptors (PChRs), because of their strategic localization at the bifurcation of the common carotid artery and along the aortic arch, play an important protective role against hypoxia. Stimulation of PChRs evokes hyperventilation and hypertension to maintain adequate oxygenation of critical organs. A relationship between increased sensitivity of PChRs (hyperreflexia) and exercise intolerance (ExIn) in patients with heart failure (HF) has been previously reported. Moreover, some studies employing an acute blockade of PChRs (e.g., using oxygen or opioids) demonstrated improvement in exercise capacity, suggesting that hypertonicity is also involved in the development of ExIn in HF. Nonetheless, the precise mechanisms linking dysfunctional PChRs to ExIn remain unclear. From the clinical perspective, there are two main factors limiting exercise capacity in HF patients: subjective perception of dyspnoea and muscle fatigue. Both have many determinants that might be influenced by abnormal signalling from PChRs, including: exertional hyperventilation, oscillatory ventilation, ergoreceptor oversensitivity, and augmented sympathetic tone. The latter results in reduced muscle perfusion and altered muscle structure. In this review, we intend to present the milieu of abnormalities tied to malfunctioning PChRs and discuss their role in the complex relationships leading, ultimately, to ExIn.
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Affiliation(s)
- Katarzyna Kulej-Lyko
- Institute of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland
- Department of Cardiology, University Clinical Hospital, Wroclaw, Poland
- *Correspondence: Katarzyna Kulej-Lyko,
| | - Piotr Niewinski
- Institute of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland
- Department of Cardiology, University Clinical Hospital, Wroclaw, Poland
| | - Stanislaw Tubek
- Institute of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland
- Department of Cardiology, University Clinical Hospital, Wroclaw, Poland
| | - Piotr Ponikowski
- Institute of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland
- Department of Cardiology, University Clinical Hospital, Wroclaw, Poland
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38
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Kato T, Noda T, Tanaka S, Yagasaki H, Iwama M, Tanihata S, Arai M, Minatoguchi S, Okura H. Impact of accelerated washout of Technetium-99m-sestamibi on exercise tolerance in patients with acute coronary syndrome: single-center experience. Heart Vessels 2022; 37:1506-1515. [PMID: 35344069 DOI: 10.1007/s00380-022-02058-3] [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: 10/28/2021] [Accepted: 03/11/2022] [Indexed: 11/25/2022]
Abstract
Technetium-99m-sestamibi (99mTc-sestamibi) single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) in patients with acute coronary syndrome (ACS) could be used to assess area-at-risks, as well as myocardial infarct or saved sizes. In patients with ACS, accelerated washout of 99mTc-sestamibi during early and delayed imaging in the acute phase may suggest mitochondrial dysfunction in the injured but salvaged myocardium. However, the link between 99mTc-sestamibi accelerated washout and exercise tolerance is unknown. The purpose of this study was to investigate a possible association between 99mTc-sestamibi accelerated washout and exercise tolerance in acute ACS patients as they progressed into the chronic phase. One hundred and sixty-five patients with ACS who underwent 99mTc-sestamibi SPECT MPI during the acute phase were recruited. On this basis, we calculated the total perfusion deficits (TPDs) for early (1 h after tracer injection) and delayed (4 h after tracer injection) images using automated quantification software. We then subtracted the early TPDs from the delayed TPDs to calculate the ΔTPD. We conducted a cardiopulmonary exercise test in acute and chronic phases. We divided two groups according to the median ΔTPD (the ΔTPD ≥ 4 group and the ΔTPD < 4 group) and compared anaerobic threshold (AT; ml/kg/min) between the groups. For anaerobic threshold (AT) improvement in data analysis, we employed multivariate logistic regression analysis. A total of 101 ST-segment elevation myocardial infarctions, 36 non-ST-elevation myocardial infarctions, and 28 unstable angina pectoris events were reported as ACS. From acute phase (10.8 ± 4.2 ml/kg/min) to chronic phase (11.9 ± 2.3 ml/kg/min), the AT in the ΔTPD ≥ 4 group was significantly increased (p < 0.0001). This trend was also seen in the ΔTPD < 4 group from acute (11.4 ± 1.8 ml/kg/min) to chronic phase (12.1 ± 2.2 ml/kg/min, p = 0.015). AT was lower in the ΔTPD ≥ 4 group in the acute phase (p = 0.027), but there was no difference in AT between the two groups in the chronic phase (p = 0.60). ΔTPD and the absence of diabetes were both independent predictors of AT improvement in multivariate logistic regression analysis. Receiver-operating characteristic curve analysis determined that ΔTPD = 6 was the best cut-off value, with 60.0% sensitivity and 71.4% specificity, respectively. The accelerated washout of 99mTc-sestamibi in patients with ACS during the acute phase could help to predict improvement in exercise tolerance in the chronic phase.
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Affiliation(s)
- Takashi Kato
- Department of Cardiology, Gifu Prefectural General Medical Center, Noisshiki 4-6-1, Gifu, Gifu, 500-8717, Japan
| | - Toshiyuki Noda
- Department of Cardiology, Gifu Prefectural General Medical Center, Noisshiki 4-6-1, Gifu, Gifu, 500-8717, Japan.
| | | | - Hiroto Yagasaki
- Department of Cardiology, Gifu Prefectural General Medical Center, Noisshiki 4-6-1, Gifu, Gifu, 500-8717, Japan
| | - Makoto Iwama
- Department of Cardiology, Gifu Prefectural General Medical Center, Noisshiki 4-6-1, Gifu, Gifu, 500-8717, Japan
| | - Shintaro Tanihata
- Department of Cardiology, Gifu Prefectural General Medical Center, Noisshiki 4-6-1, Gifu, Gifu, 500-8717, Japan
| | - Masazumi Arai
- Department of Cardiology, Gifu Prefectural General Medical Center, Noisshiki 4-6-1, Gifu, Gifu, 500-8717, Japan
| | | | - Hiroyuki Okura
- Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan
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Weber RE, Schulze KM, Colburn TD, Horn AG, Hageman KS, Ade CJ, Hall SE, Sandner P, Musch TI, Poole DC. Capillary hemodynamics and contracting skeletal muscle oxygen pressures in male rats with heart failure: Impact of soluble guanylyl cyclase activator. Nitric Oxide 2022; 119:1-8. [PMID: 34871799 PMCID: PMC9469501 DOI: 10.1016/j.niox.2021.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 10/21/2021] [Accepted: 12/02/2021] [Indexed: 11/26/2022]
Abstract
In heart failure with reduced ejection fraction (HFrEF), nitric oxide-soluble guanylyl cyclase (sGC) pathway dysfunction impairs skeletal muscle arteriolar vasodilation and thus capillary hemodynamics, contributing to impaired oxygen uptake (V̇O2) kinetics. Targeting this pathway with sGC activators offers a new treatment approach to HFrEF. We tested the hypotheses that sGC activator administration would increase the O2 delivery (Q̇O2)-to-V̇O2 ratio in the skeletal muscle interstitial space (PO2is) of HFrEF rats during twitch contractions due, in part, to increases in red blood cell (RBC) flux (fRBC), velocity (VRBC), and capillary hematocrit (Hctcap). HFrEF was induced in male Sprague-Dawley rats via myocardial infarction. After 3 weeks, rats were treated with 0.3 mg/kg of the sGC activator BAY 60-2770 (HFrEF + BAY; n = 11) or solvent (HFrEF; n = 9) via gavage b.i.d for 5 days prior to phosphorescence quenching (PO2is, in contracting muscle) and intravital microscopy (resting) measurements in the spinotrapezius muscle. Intravital microscopy revealed higher fRBC (70 ± 9 vs 25 ± 8 RBC/s), VRBC (490 ± 43 vs 226 ± 35 μm/s), Hctcap (16 ± 1 vs 10 ± 1%) and a greater number of capillaries supporting flow (91 ± 3 vs 82 ± 3%) in HFrEF + BAY vs HFrEF (all P < 0.05). Additionally, PO2is was especially higher during 12-34s of contractions in HFrEF + BAY vs HFrEF (P < 0.05). Our findings suggest that sGC activators improved resting Q̇O2 via increased fRBC, VRBC, and Hctcap allowing for better Q̇O2-to-V̇O2 matching during the rest-contraction transient, supporting sGC activators as a potential therapeutic to target skeletal muscle vasomotor dysfunction in HFrEF.
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Affiliation(s)
- Ramona E Weber
- Department of Kinesiology, Kansas State University, Manhattan, KS, USA.
| | - Kiana M Schulze
- Department of Kinesiology, Kansas State University, Manhattan, KS, USA
| | - Trenton D Colburn
- Department of Kinesiology, Kansas State University, Manhattan, KS, USA
| | - Andrew G Horn
- Department of Kinesiology, Kansas State University, Manhattan, KS, USA
| | - K Sue Hageman
- Department of Anatomy and Physiology, Kansas State University, Manhattan, KS, USA
| | - Carl J Ade
- Department of Kinesiology, Kansas State University, Manhattan, KS, USA
| | - Stephanie E Hall
- Department of Anatomy and Physiology, Kansas State University, Manhattan, KS, USA
| | - Peter Sandner
- Bayer AG, Cardiology Research, Wuppertal, Germany and Hannover Medical School, Department of Pharmacology, Hannover, Germany
| | - Timothy I Musch
- Department of Kinesiology, Kansas State University, Manhattan, KS, USA; Department of Anatomy and Physiology, Kansas State University, Manhattan, KS, USA
| | - David C Poole
- Department of Kinesiology, Kansas State University, Manhattan, KS, USA; Department of Anatomy and Physiology, Kansas State University, Manhattan, KS, USA
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40
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Visioli F, Ingram A, Beckman JS, Magnusson KR, Hagen TM. Strategies to protect against age-related mitochondrial decay: Do natural products and their derivatives help? Free Radic Biol Med 2022; 178:330-346. [PMID: 34890770 DOI: 10.1016/j.freeradbiomed.2021.12.008] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 11/24/2021] [Accepted: 12/04/2021] [Indexed: 12/12/2022]
Abstract
Mitochondria serve vital roles critical for overall cellular function outside of energy transduction. Thus, mitochondrial decay is postulated to be a key factor in aging and in age-related diseases. Mitochondria may be targets of their own decay through oxidative damage. However, treating animals with antioxidants has been met with only limited success in rejuvenating mitochondrial function or in increasing lifespan. A host of nutritional strategies outside of using traditional antioxidants have been devised to promote mitochondrial function. Dietary compounds are under study that induce gene expression, enhance mitochondrial biogenesis, mitophagy, or replenish key metabolites that decline with age. Moreover, redox-active compounds may now be targeted to mitochondria which improve their effectiveness. Herein we review the evidence that representative dietary effectors modulate mitochondrial function by stimulating their renewal or reversing the age-related loss of key metabolites. While in vitro evidence continues to accumulate that many of these compounds benefit mitochondrial function and/or prevent their decay, the results using animal models and, in some instances human clinical trials, are more mixed and sometimes even contraindicated. Thus, further research on optimal dosage and age of intervention are warranted before recommending potential mitochondrial rejuvenating compounds for human use.
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Affiliation(s)
- Francesco Visioli
- Department of Molecular Medicine, University of Padova, Italy; IMDEA-Food, Madrid, Spain
| | - Avery Ingram
- Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331, USA; Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR, 97331, USA
| | - Joseph S Beckman
- Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331, USA; Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR, 97331, USA
| | - Kathy R Magnusson
- Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331, USA
| | - Tory M Hagen
- Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331, USA; Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR, 97331, USA.
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41
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Mitrouska I, Bolaki M, Vaporidi K, Georgopoulos D. Respiratory system as the main determinant of dyspnea in patients with pulmonary hypertension. Pulm Circ 2022; 12:e12060. [PMID: 35506092 PMCID: PMC9053013 DOI: 10.1002/pul2.12060] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 03/02/2022] [Accepted: 03/06/2022] [Indexed: 11/10/2022] Open
Abstract
Dyspnea on exertion is a devastating symptom, commonly observed in patients with pulmonary hypertension (PH). The pathophysiology of dyspnea in these patients has been mainly attributed to cardiovascular determinants and isolated abnormalities of the respiratory system during exercise, neglecting the contribution of the control of the breathing system. The aim of this review is to provide a novel approach to the interpretation of dyspnea in patients with PH, focused on the impact of the control of the breathing system during exercise. Exercise through multiple mechanisms affects the (1) ventilatory demands, as dictated by respiratory center activity, (2) actual ventilation, and (3) metabolic hyperbola. In patients with PH, exertional dyspnea can be explained by exercise-induced alterations in these variables. Compared to healthy subjects, at a given CO2 production during exercise, ventilatory demands in patients with PH are higher due to metabolic acidosis (early reaching the anaerobic threshold), hypoxemia, and excessive upward movement of metabolic hyperbola owing to abnormal exercise response of dead space to tidal volume ratio. Simultaneously, dynamic hyperinflation and respiratory muscles weakness decreases the actual ventilation for a given respiratory center activity, creating a dissociation between demands and ventilation. Consequently, a progressive increase in ventilatory demands and respiratory center activity occurs during exercise. The forebrain projection of high respiratory center activity causes exertional dyspnea despite the relatively low ventilation and significant ventilatory reserve. This type of analysis suggests that the respiratory system is the main determinant of exertional dyspnea in patients with PH, with the cardiovascular system being an indirect contributor.
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Affiliation(s)
- Ioanna Mitrouska
- Department of Pulmonary Medicine, University Hospital of Heraklion, Medical SchoolUniversity of CreteHeraklionCreteGreece
| | - Maria Bolaki
- Department of Intensive Care Medicine, University Hospital of Heraklion, Medical SchoolUniversity of CreteHeraklionCreteGreece
| | - Katerina Vaporidi
- Department of Intensive Care Medicine, University Hospital of Heraklion, Medical SchoolUniversity of CreteHeraklionCreteGreece
| | - Dimitris Georgopoulos
- Department of Intensive Care Medicine, University Hospital of Heraklion, Medical SchoolUniversity of CreteHeraklionCreteGreece
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Sadek Z, Ahmaidi S, Youness M, Awada C, Joumaa WH, Ramadan W. Combining aerobic interval, inspiratory and resistance trainings induces better cardiac remodelling and exercise capacity in heart failure patients. EUROPEAN JOURNAL OF PHYSIOTHERAPY 2021. [DOI: 10.1080/21679169.2021.2017477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Zahra Sadek
- Rammal Hassan Rammal Laboratory « PhyToxE Physio-toxicité environnemental », Faculty of Sciences, Lebanese University, Nabatieh, Lebanon
- Laboratory EA-3300 (APERE) « Adaptations Physiologiques à l’Exercice et Réadaptation à l’Effort », Picardie Jules Verne University, Amiens, France
- Physical Therapy Department, Islamic University of Lebanon, Beirut, Lebanon
| | - Said Ahmaidi
- Laboratory EA-3300 (APERE) « Adaptations Physiologiques à l’Exercice et Réadaptation à l’Effort », Picardie Jules Verne University, Amiens, France
| | - Mahmoud Youness
- Medical Research Center of Beirut Cardiac Institute, Beirut, Lebanon
| | - Charifa Awada
- Rammal Hassan Rammal Laboratory « PhyToxE Physio-toxicité environnemental », Faculty of Sciences, Lebanese University, Nabatieh, Lebanon
| | - Wissam H. Joumaa
- Rammal Hassan Rammal Laboratory « PhyToxE Physio-toxicité environnemental », Faculty of Sciences, Lebanese University, Nabatieh, Lebanon
| | - Wiam Ramadan
- Rammal Hassan Rammal Laboratory « PhyToxE Physio-toxicité environnemental », Faculty of Sciences, Lebanese University, Nabatieh, Lebanon
- Lebanese Institutes for Biomedical Research and Application (LIBRA), Lebanese International University and International University of Beirut (BIU), Beirut, Lebanon
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Takada S, Sabe H, Kinugawa S. Treatments for skeletal muscle abnormalities in heart failure: sodium-glucose transporter 2 and ketone bodies. Am J Physiol Heart Circ Physiol 2021; 322:H117-H128. [PMID: 34860594 DOI: 10.1152/ajpheart.00100.2021] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Various skeletal muscle abnormalities are known to occur in heart failure (HF), and are closely associated with exercise intolerance. Particularly, abnormal energy metabolism caused by mitochondrial dysfunction in skeletal muscle is a cause of decreased endurance exercise capacity. However, to date, no specific drug treatment has been established for the skeletal muscle abnormalities and exercise intolerance occurring in HF patients. Sodium-glucose transporter 2 (SGLT2) inhibitors promote glucose excretion by suppressing glucose reabsorption in the renal tubules, which has a hypoglycemic effect independent of insulin secretion. Recently, large clinical trials have demonstrated that treatment with SGLT2 inhibitors suppresses cardiovascular events in patients who have HF with systolic dysfunction. Mechanisms of the therapeutic effects of SGLT2 inhibitors for HF have been suggested to be diuretic, suppression of neurohumoral factor activation, renal protection, and improvement of myocardial metabolism, but has not been clarified to date. SGLT2 inhibitors are known to increase blood ketone bodies. This suggests that they may improve the abnormal skeletal muscle metabolism in HF, i.e., improve fatty acid metabolism, suppress glycolysis, and utilize ketone bodies in mitochondrial energy production. Ultimately, they may improve aerobic metabolism in skeletal muscle, and suppress anaerobic metabolism and improve aerobic exercise capacity at the level of the anaerobic threshold. The potential actions of such SGLT2 inhibitors explain their effectiveness in HF, and may be candidates for new drug treatments aimed at improving exercise intolerance. In this review, we outlined the effects of SGLT2 inhibitors on skeletal muscle metabolism, with a particular focus on ketone metabolism.
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Affiliation(s)
- Shingo Takada
- Department of Sports Education, Faculty of Lifelong Sport, Hokusho University, Ebetsu, Hokkaido, Japan
| | - Hisataka Sabe
- Department of Molecular Biology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Shintaro Kinugawa
- Department of Experimental and Clinical Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Fukuoka, Japan
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Hotta K, Taniguchi R, Nakayama H, Yamaguchi F, Sato Y. The Effects of an Oral Nutritional Supplement with Whey Peptides and Branched-Chain Amino Acids for Cardiac Rehabilitation of Patients with Chronic Heart Failure. Int Heart J 2021; 62:1342-1347. [PMID: 34789638 DOI: 10.1536/ihj.21-102] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
The aim of the present study was to determine whether the addition of an oral nutritional supplement with whey peptides and branched-chain amino acids for cardiac rehabilitation improves cardiopulmonary function, skeletal muscle function, and metabolism in CHF patients.In this randomized, parallel-group comparative pilot study, 20 CHF patients were randomly assigned to the nutrition group (n = 10) or the control group (n = 10). At baseline and 12 weeks, we performed physical examinations, motor function evaluation, clinical laboratory tests, nutritional status assessment, and echocardiography. The primary outcome was exercise tolerance, as determined by the cardiopulmonary stress test (CPX), 6-minute walking test (6MWT), and brain natriuretic peptide (BNP) levels.During follow-up, body weight, body mass index, total muscle mass, and total lean mass did not change significantly in either group. The total fat mass significantly increased in the nutrition group (14.3 ± 5.4 kg versus 16.1 ± 5.5 kg, P < 0.001) but did not change in the control group, and the difference in the changes in total fat mass between groups was significant (-0.26 ± 0.96 kg versus 1.49 ± 0.63 kg, P < 0.001). The peakVO2 and 6-minute walk test (6 MWT) significantly increased in the nutrition group (14.6 ± 3.4 mL/minute/kg versus 15.8 ± 3.8 mL/minute/kg, P = 0.029; 346.9 ± 103.1 m versus 382.7 ± 102.1 m, P = 0.048; respectively) but did not change in the control group. The changes in peakVO2 and 6MWT did not significantly differ between the groups.The oral nutritional supplement for the treatment of CHF was effective for cardiac rehabilitation in terms of fat mass and exercise capacity.The present study demonstrated that oral nutritional supplements with whey peptides and branched-chain amino acid (BCAA) for cardiac rehabilitation in patients with chronic heart failure (CHF) increased fat mass and exercise capacity. We conclude that whey peptides and BCAA supplementation may be a useful treatment for CHF patients.
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Affiliation(s)
- Kozo Hotta
- Departments of Cardiology, Hyogo Prefectural Amagasaki General Medical Center
| | - Ryoji Taniguchi
- Departments of Cardiology, Hyogo Prefectural Amagasaki General Medical Center
| | - Hiroyuki Nakayama
- Departments of Cardiology, Hyogo Prefectural Amagasaki General Medical Center
| | - Fumitaka Yamaguchi
- Departments of Cardiology, Hyogo Prefectural Amagasaki General Medical Center
| | - Yukihito Sato
- Departments of Cardiology, Hyogo Prefectural Amagasaki General Medical Center
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Kourek C, Karatzanos E, Nanas S, Karabinis A, Dimopoulos S. Exercise training in heart transplantation. World J Transplant 2021; 11:466-479. [PMID: 34868897 PMCID: PMC8603635 DOI: 10.5500/wjt.v11.i11.466] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 08/12/2021] [Accepted: 10/27/2021] [Indexed: 02/06/2023] Open
Abstract
Heart transplantation remains the gold standard in the treatment of end-stage heart failure (HF). Heart transplantation patients present lower exercise capacity due to cardiovascular and musculoskeletal alterations leading thus to poor quality of life and reduction in the ability of daily self-service. Impaired vascular function and diastolic dysfunction cause lower cardiac output while decreased skeletal muscle oxidative fibers, enzymes and capillarity cause arteriovenous oxygen difference, leading thus to decreased peak oxygen uptake in heart transplant recipients. Exercise training improves exercise capacity, cardiac and vascular endothelial function in heart transplant recipients. Pre-rehabilitation regular aerobic or combined exercise is beneficial for patients with end-stage HF awaiting heart transplantation in order to maintain a higher fitness level and reduce complications afterwards like intensive care unit acquired weakness or cardiac cachexia. All hospitalized patients after heart transplantation should be referred to early mobilization of skeletal muscles through kinesiotherapy of the upper and lower limbs and respiratory physiotherapy in order to prevent infections of the respiratory system prior to hospital discharge. Moreover, all heart transplant recipients after hospital discharge who have not already participated in an early cardiac rehabilitation program should be referred to a rehabilitation center by their health care provider. Although high intensity interval training seems to have more benefits than moderate intensity continuous training, especially in stable transplant patients, individualized training based on the abilities and needs of each patient still remains the most appropriate approach. Cardiac rehabilitation appears to be safe in heart transplant patients. However, long-term follow-up data is incomplete and, therefore, further high quality and adequately-powered studies are needed to demonstrate the long-term benefits of exercise training in this population.
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Affiliation(s)
- Christos Kourek
- Clinical Ergospirometry, Exercise & Rehabilitation Laboratory, Evaggelismos Hospital, Athens 10676, Attica, Greece
| | - Eleftherios Karatzanos
- Clinical Ergospirometry, Exercise & Rehabilitation Laboratory, Evaggelismos Hospital, Athens 10676, Attica, Greece
| | - Serafim Nanas
- Clinical Ergospirometry, Exercise & Rehabilitation Laboratory, Evaggelismos Hospital, Athens 10676, Attica, Greece
| | - Andreas Karabinis
- Cardiac Surgery Intensive Care Unit, Onassis Cardiac Surgery Center, Athens 17674, Greece
| | - Stavros Dimopoulos
- Clinical Ergospirometry, Exercise & Rehabilitation Laboratory, Evaggelismos Hospital, Athens 10676, Attica, Greece
- Cardiac Surgery Intensive Care Unit, Onassis Cardiac Surgery Center, Athens 17674, Greece
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Zhou Z, Zhang K, Liu Z, Gao X, Huang K, Chen C, Wang D, Yang Q, Long Q. ATPAF1 deficiency impairs ATP synthase assembly and mitochondrial respiration. Mitochondrion 2021; 60:129-141. [PMID: 34375736 DOI: 10.1016/j.mito.2021.08.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 07/08/2021] [Accepted: 08/05/2021] [Indexed: 11/28/2022]
Abstract
ATP11p and ATP12p are two nuclear-encoded mitochondrial chaperone proteins required for assembling the F1Fo-ATP synthase F1 sector. ATPAF1 and ATPAF2 are the mammalian homologs of ATP11p and ATP12p. However, the biochemical and physiological relevance of ATPAF1 and ATPAF2 in animal tissues with high energy-dependence remains unclear. To explore the in vivo role of ATP assembly and the effects of ATP synthase deficiency in animals, we have generated knockout (KO) mouse models of these assembly factors using CRISPR/Cas9 technology. While the Atpaf2-KO mice were embryonically lethal, Atpaf1-KO mice grew to adulthood but with smaller body sizes and elevated blood lactate later in life. We specifically investigated how ATPAF1 deficiency may affect ATP synthase biogenesis and mitochondrial respiration in the mouse heart, an organ highly energy-dependent. Western blots and Blue-Native electrophoresis (BN-PAGE) demonstrated a decreased F1 content and ATP synthase dimers in the Atpaf1-KO heart. Mitochondria from ATPAF1-deficient hearts showed ultrastructural abnormalities with condensed degenerated mitochondria, loss of cristae, and impaired respiratory capacity. ATP synthase deficiency also leads to impaired autophagy and mitochondrial dynamic. Consequently, decreased cardiac function was exhibited in adult Atpaf1-KO mice. The results provide strong support that ATPAF1 is essential for ATP synthase assembly and mitochondrial oxidative phosphorylation, thus playing a crucial role in maintaining cardiac structure and function in animals.
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Affiliation(s)
- Zhou Zhou
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, China
| | - Kailiang Zhang
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, China
| | - Zhiheng Liu
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, China
| | - Xu Gao
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, China
| | - Kai Huang
- Department of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Chen Chen
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, China
| | - Daowen Wang
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, China
| | - Qinglin Yang
- Cardiovascular Center of Excellence and Department of Pharmacology, Louisiana State University Health Science Center-New Orleans, LA 70112, United States; Department of Nutrition Science, University of Alabama at Birmingham, Birmingham, AL 35294, United States.
| | - Qinqiang Long
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, China; Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China; Department of Nutrition Science, University of Alabama at Birmingham, Birmingham, AL 35294, United States.
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47
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Heart Failure Severity Stratification Beyond INTERMACS Profiles: A Step Toward Optimal Left Ventricular Assist Device Timing. ASAIO J 2021; 67:554-560. [PMID: 33470635 DOI: 10.1097/mat.0000000000001352] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022] Open
Abstract
The purpose of this analysis is to determine whether pectoralis muscle measures quantified on pre left ventricular assist device (LVAD) computerized tomography (CT) scans can identify subgroups of patients with differential disease severity within each Interagency Registry for Mechanical Circulatory Support (INTERMACS) profile. Patients with chest CTs performed ≤3 months before LVAD implantation at University of Minnesota (n = 143) and Houston Methodist Hospital (n = 133) were identified from the larger LVAD cohorts (University of Minnesota n = 353, Houston Methodist =278). Unilateral Pectoralis muscle mass indexed to body surface area and pectoralis muscle attenuation were measured on preoperative chest CT scans. Patients within each INTERMACS profile were separated into HIGH and LOW PEC muscle groups. Kaplan-Meier and multivariable cox regression analyses were performed to compare mortality among INTERMACS profiles by HIGH and LOW PEC muscle groups. INTERMACS 3 and 4 patients in the HIGH PEC groups had the highest survival on LVAD support (1 year survival 85% vs. 68%, log rank P = 0.0001). Being in this group was associated with a 60% reduction in the hazards rate (HR) of death after LVAD (adjusted HR 0.40, 95% confidence interval 0.25-0.62). Additionally, renal function deterioration in the year before LVAD was associated with lower INTERMACS profiles and lower measured pectoralis muscle tissue attenuation at the time of LVAD implantation. INTERMACS 3 and 4 patients with the highest pectoralis muscle measures had the best survival after LVAD. The association between renal function deterioration and sarcopenia suggests these muscle changes are progressive. Computerized tomography quantification of sarcopenia may help identify optimal LVAD implantation timing.
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48
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Abstract
PURPOSE OF REVIEW Exercise causes various dynamic changes in all body parts either in healthy subject or in heart failure (HF) patients. The present review of current knowledge about HF patients with reduced ejection fraction focuses on dynamic changes along a "metabo-hemodynamic" perspective. RECENT FINDINGS Studies on the dynamic changes occurring during exercise span many years. Thanks to the availability of advanced methods, it is nowadays possible to properly characterize respiratory, hemodynamic, and muscular function adjustments and their mismatch with the pulmonary and systemic circulations. Exercise is a dynamic event that involves several body functions. In HF patients, it is important to know at what level the limitation takes place in order to better manage these patients and to optimize therapeutic strategies.
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49
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Tickle PG, Hendrickse PW, Weightman A, Nazir MH, Degens H, Egginton S. Impaired skeletal muscle fatigue resistance during cardiac hypertrophy is prevented by functional overload- or exercise-induced functional capillarity. J Physiol 2021; 599:3715-3733. [PMID: 34107075 DOI: 10.1113/jp281377] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Accepted: 06/04/2021] [Indexed: 11/08/2022] Open
Abstract
KEY POINTS Capillary rarefaction is hypothesized to contribute to impaired exercise tolerance in cardiovascular disease, but it remains a poorly exploited therapeutic target for improving skeletal muscle performance. Using an abdominal aortic coarctation rat model of compensatory cardiac hypertrophy, we determine the efficacy of aerobic exercise for the prevention of, and mechanical overload for, restoration of hindlimb muscle fatigue resistance and microvascular impairment in the early stages of heart disease. Impaired muscle fatigue resistance was found after development of cardiac hypertrophy, but this impairment was prevented by low-intensity aerobic exercise and recovered after mechanical stretch due to muscle overload. Changes in muscle fatigue resistance were closely related to functional (i.e. perfused) microvascular density, independent of arterial blood flow, emphasizing the critical importance of optimal capillary diffusion for skeletal muscle function. Pro-angiogenic therapies are an important tool for improving skeletal muscle function in the incipient stages of heart disease. ABSTRACT Microvascular rarefaction may contribute to declining skeletal muscle performance in cardiac and vascular diseases. It remains uncertain to what extent microvascular rarefaction occurs in the earliest stages of these conditions, if impaired blood flow is an aggravating factor and whether angiogenesis restores muscle performance. To investigate this, the effects of aerobic exercise (voluntary wheel running) and functional muscle overload on the performance, femoral blood flow (FBF) and microvascular perfusion of the extensor digitorum longus (EDL) were determined in a chronic rat model of compensatory cardiac hypertrophy (CCH, induced by surgically imposed abdominal aortic coarctation). CCH was associated with hypertension (P = 0.001 vs. Control) and increased relative heart mass (P < 0.001). Immediately upon placing the aortic band (i.e. before development of CCH), post-fatigue test FBF was reduced (P < 0.003), coinciding with attenuated fatigue resistance (P = 0.039) indicating an acute arterial perfusion constraint on muscle performance. While FBF was normalized during CCH in chronic groups (P > 0.05) fatigue resistance remained reduced (P = 0.039) and was associated with reduced (P = 0.009) functional capillarity after development of CCH without intervention, indicating a microvascular limitation to muscle performance. Normalization of functional capillarity after aerobic exercise (P = 0.065) and overload (P = 0.329) in CCH coincided with restoration to control levels of muscle fatigue resistance (P > 0.999), although overload-induced EDL hypertrophy (P = 0.027) and wheel-running velocity and duration (both P < 0.05) were attenuated after aortic banding. These data show that reductions in skeletal muscle performance during CCH can be countered by improving functional capillarity, providing a therapeutic target to improve skeletal muscle function in chronic diseases.
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Affiliation(s)
- Peter G Tickle
- School of Biomedical Sciences, University of Leeds, Leeds, UK
| | - Paul W Hendrickse
- Department of Life Sciences, Research Centre for Musculoskeletal Science & Sports Medicine, Manchester Metropolitan University, Manchester, UK.,Institute of Sport Science and Innovations, Lithuanian Sports University, Kaunas, Lithuania
| | - Andrew Weightman
- Department of Mechanical, Aerospace and Civil Engineering, University of Manchester, Manchester, UK
| | - M Hakam Nazir
- School of Biomedical Sciences, University of Leeds, Leeds, UK
| | - Hans Degens
- Department of Life Sciences, Research Centre for Musculoskeletal Science & Sports Medicine, Manchester Metropolitan University, Manchester, UK.,Institute of Sport Science and Innovations, Lithuanian Sports University, Kaunas, Lithuania
| | - Stuart Egginton
- School of Biomedical Sciences, University of Leeds, Leeds, UK
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50
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Konishi M, Akiyama E, Matsuzawa Y, Sato R, Kikuchi S, Nakahashi H, Maejima N, Iwahashi N, Kosuge M, Ebina T, Hibi K, Misumi T, von Haehling S, Anker SD, Tamura K, Kimura K. Prognostic impact of muscle and fat mass in patients with heart failure. J Cachexia Sarcopenia Muscle 2021; 12:568-576. [PMID: 33939328 PMCID: PMC8200420 DOI: 10.1002/jcsm.12702] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 01/16/2021] [Accepted: 03/15/2021] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Cachexia, characterized by loss of muscle with or without loss of fat mass, is a poor prognostic factor in patients with heart failure (HF). However, there is limited investigation on the prognostic impact of muscle and fat mass separately in HF. We hypothesized that muscle and fat mass have different effects on the prognosis of HF. METHODS This was an observational cohort study of 418 patients (59% were men) admitted with a diagnosis of HF (71 ± 13 years [mean ± standard deviation]), with left ventricular ejection fraction (LVEF) of 39 ± 16%, including 31.3%, 14.8%, and 53.8% of patients with preserved LVEF (LVEF ≥ 50%), mid-range LVEF (40-50%), and reduced (<40%) LVEF, respectively. Dual-energy X-ray absorptiometry was performed with the patients in the stable state after decongestion therapy. RESULTS The mean body mass index of patients was 22.1 ± 4.6 kg/m2 , and the mean appendicular skeletal mass (ASM) index was 6.88 ± 1.23 kg/m2 in men and 5.59 ± 0.92 in women; 54.1% of the patients showed reduced muscle mass defined by the international cut-off value (7.0 kg/m2 for men and 5.4 for women). The mean fat mass was 20.4 ± 7.2% in men and 27.2 ± 8.6% in women. During a median follow-up of 37 months, 92 (22.0%) of 418 patients with HF died (1 and 3 year mortality: 8.4% and 17.3%, respectively). Lower values of both skeletal muscle and fat mass were independently associated with increased risk of mortality adjusted for age, sex, haemoglobin, New York Heart Association functional class, and height squared (hazard ratio with 95% confidence interval of 0.825 [0.747-0.908] per 1 kg increase of ASM, P < 0.001, and 0.954 [0.916-0.993] per 1 kg increase of fat mass, P = 0.018, respectively). CONCLUSIONS More than half of the patients with HF showed reduced muscle mass. Lower values of both muscle and fat mass were associated with higher mortality in HF.
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Affiliation(s)
- Masaaki Konishi
- Division of CardiologyYokohama City University Medical CenterYokohamaJapan
- Department of Medical Science and Cardiorenal MedicineYokohama City University Graduate School of MedicineYokohamaJapan
| | - Eiichi Akiyama
- Division of CardiologyYokohama City University Medical CenterYokohamaJapan
| | - Yasushi Matsuzawa
- Division of CardiologyYokohama City University Medical CenterYokohamaJapan
| | - Ryosuke Sato
- Division of CardiologyYokohama City University Medical CenterYokohamaJapan
| | - Shinnosuke Kikuchi
- Division of CardiologyYokohama City University Medical CenterYokohamaJapan
| | - Hidefumi Nakahashi
- Division of CardiologyYokohama City University Medical CenterYokohamaJapan
| | - Nobuhiko Maejima
- Division of CardiologyYokohama City University Medical CenterYokohamaJapan
| | - Noriaki Iwahashi
- Division of CardiologyYokohama City University Medical CenterYokohamaJapan
| | - Masami Kosuge
- Division of CardiologyYokohama City University Medical CenterYokohamaJapan
| | - Toshiaki Ebina
- Division of CardiologyYokohama City University Medical CenterYokohamaJapan
| | - Kiyoshi Hibi
- Division of CardiologyYokohama City University Medical CenterYokohamaJapan
| | - Toshihiro Misumi
- Department of BiostatisticsYokohama City University School of MedicineYokohamaJapan
| | - Stephan von Haehling
- Department of Cardiology and Pneumology; German Center for Cardiovascular Research (DZHK), partner site GöttingenUniversity of Göttingen Medical CenterGöttingenGermany
| | - Stefan D. Anker
- Department of Cardiology (CVK); and Berlin Institute of Health Center for Regenerative Therapies (BCRT); German Centre for Cardiovascular Research (DZHK) partner site BerlinCharité Universitätsmedizin BerlinBerlinGermany
| | - Kouichi Tamura
- Department of Medical Science and Cardiorenal MedicineYokohama City University Graduate School of MedicineYokohamaJapan
| | - Kazuo Kimura
- Division of CardiologyYokohama City University Medical CenterYokohamaJapan
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