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Dalane W. Kitzman - One of the best experts on this subject based on the ideXlab platform.
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regional adipose distribution and its relationship to Exercise Intolerance in older obese patients who have heart failure with preserved ejection fraction
Jacc-Heart Failure, 2018Co-Authors: Mark J. Haykowsky, Peter H. Brubaker, Bharathi Upadhya, Barbara J Nicklas, Gregory W Hundley, Tina E Brinkley, Thomas J Becton, Michael D Nelson, Haiying Chen, Dalane W. KitzmanAbstract:Abstract Objectives This study sought to test the hypothesis that older obese patients with heart failure with preserved ejection fraction (HFpEF) have significantly greater abdominal, cardiac, and intermuscular fat than healthy, age-matched controls, out of proportion to total body fat, and that these abnormalities are associated with objective measurements of physical function. Background Recent studies indicate that excess total body adipose tissue contributes to Exercise Intolerance in patients with HFpEF. However, the impact of the pattern of regional (abdominal, cardiac, intermuscular) adipose deposition on Exercise Intolerance in patients with HFpEF is unknown. Methods We measured total body adiposity (using dual-energy x-ray absorptiometry) and regional adiposity (using cardiac magnetic resonance), peak oxygen uptake (Vo2), 6-min walk distance (6MWD), short physical performance battery (SPPB), and leg press power in 100 older obese patients with HFpEF and 61 healthy controls (HCs) and adjusted for age, sex, race, and body surface area. Results Peak Vo2 (15.7 ± 0.4 ml/kg/min vs. 23.0 ± 0.6 ml/kg/min, respectively; p Conclusions In metabolic obese HFpEF, the pattern of regional adipose deposition may have important adverse consequences beyond total body adiposity. Interventions targeting intra-abdominal and intermuscular fat could potentially improve Exercise Intolerance. (Exercise Intolerance in Elderly Patients With Diastolic Heart Failure [SECRET]; NCT00959660)
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Determinants of Exercise Intolerance in patients with heart failure and reduced or preserved ejection fraction.
Journal of applied physiology (Bethesda Md. : 1985), 2015Co-Authors: Mark J. Haykowsky, Corey R. Tomczak, Jessica M. Scott, D. Ian Paterson, Dalane W. KitzmanAbstract:This mini-review summarizes the literature regarding the mechanisms of Exercise Intolerance in patients with heart failure and reduced or preserved ejection fraction (HFREF and HFPEF, respectively)...
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Sarcopenic Obesity and the Pathogenesis of Exercise Intolerance in Heart Failure With Preserved Ejection Fraction
Current heart failure reports, 2015Co-Authors: Bharathi Upadhya, Mark J. Haykowsky, Joel Eggebeen, Dalane W. KitzmanAbstract:Heart failure with preserved ejection fraction (HFpEF) is the most common form of heart failure (HF) in older adults. The primary chronic symptom in patients with HFpEF, even when well compensated, is severe Exercise Intolerance. Cardiac and peripheral functions contribute equally to Exercise Intolerance in HFpEF, though the latter has been the focus of fewer studies. Of note, multiple studies with Exercise training have shown that Exercise Intolerance can improve significantly in the absence of improvements in Exercise cardiac output, indicating a role of peripheral, noncardiac adaptations. In addition, clinical drug trials performed to date in HFpEF, all of which have focused on influencing cardiovascular function, have not been positive on primary clinical outcomes and most have not improved Exercise capacity. Mounting evidence indicates that sarcopenic obesity, characterized by the coexistence of excess fat mass and decreased muscle mass, could contribute to the pathophysiology of Exercise Intolerance in older HFpEF patients and may provide avenues for novel treatments.
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skeletal muscle abnormalities and Exercise Intolerance in older patients with heart failure and preserved ejection fraction
American Journal of Physiology-heart and Circulatory Physiology, 2014Co-Authors: Dalane W. Kitzman, Joel Eggebeen, Timothy M Morgan, Barbara J Nicklas, William E Kraus, Mary F Lyles, Mark J. HaykowskyAbstract:Heart failure (HF) with preserved ejection fraction (HFPEF) is the most common form of HF in older persons. The primary chronic symptom in HFPEF is severe Exercise Intolerance, and its pathophysiol...
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determinants of Exercise Intolerance in elderly heart failure patients with preserved ejection fraction
Journal of the American College of Cardiology, 2011Co-Authors: Mark J. Haykowsky, Peter H. Brubaker, Jerry M John, Kathryn P Stewart, Timothy M Morgan, Dalane W. KitzmanAbstract:Objectives The purpose of this study was to determine the mechanisms responsible for reduced aerobic capacity (peak V o 2 ) in patients with heart failure with preserved ejection fraction (HFPEF). Background HFPEF is the predominant form of heart failure in older persons. Exercise Intolerance is the primary symptom among patients with HFPEF and a major determinant of reduced quality of life. In contrast to patients with heart failure and reduced ejection fraction, the mechanism of Exercise Intolerance in HFPEF is less well understood. Methods Left ventricular volumes (2-dimensional echocardiography), cardiac output, V o 2 , and calculated arterial-venous oxygen content difference (A-V o 2 Diff) were measured at rest and during incremental, exhaustive upright cycle Exercise in 48 HFPEF patients (age 69 ± 6 years) and 25 healthy age-matched controls. Results In HFPEF patients compared with healthy controls, V o 2 was reduced at peak Exercise (14.3 ± 0.5 ml·kg·min −1 vs. 20.4 ± 0.6 ml·kg·min −1 ; p −1 vs. 7.6 ± 0.2 l·min −1 ; p o 2 Diff (17 ± 0.4 ml·dl −1 vs. 19 ± 0.4 ml·dl −1 , p o 2 was the change in A-V o 2 Diff from rest to peak Exercise (A-V o 2 Diff reserve) for both HFPEF patients (partial correlate, 0.58; standardized β coefficient, 0.66; p = 0.0002) and healthy controls (partial correlate, 0.61; standardized β coefficient, 0.41; p = 0.005). Conclusions Both reduced cardiac output and A-V o 2 Diff contribute significantly to the severe Exercise Intolerance in elderly HFPEF patients. The finding that A-V o 2 Diff reserve is an independent predictor of peak V o 2 suggests that peripheral, noncardiac factors are important contributors to Exercise Intolerance in these patients.
Mark J. Haykowsky - One of the best experts on this subject based on the ideXlab platform.
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regional adipose distribution and its relationship to Exercise Intolerance in older obese patients who have heart failure with preserved ejection fraction
Jacc-Heart Failure, 2018Co-Authors: Mark J. Haykowsky, Peter H. Brubaker, Bharathi Upadhya, Barbara J Nicklas, Gregory W Hundley, Tina E Brinkley, Thomas J Becton, Michael D Nelson, Haiying Chen, Dalane W. KitzmanAbstract:Abstract Objectives This study sought to test the hypothesis that older obese patients with heart failure with preserved ejection fraction (HFpEF) have significantly greater abdominal, cardiac, and intermuscular fat than healthy, age-matched controls, out of proportion to total body fat, and that these abnormalities are associated with objective measurements of physical function. Background Recent studies indicate that excess total body adipose tissue contributes to Exercise Intolerance in patients with HFpEF. However, the impact of the pattern of regional (abdominal, cardiac, intermuscular) adipose deposition on Exercise Intolerance in patients with HFpEF is unknown. Methods We measured total body adiposity (using dual-energy x-ray absorptiometry) and regional adiposity (using cardiac magnetic resonance), peak oxygen uptake (Vo2), 6-min walk distance (6MWD), short physical performance battery (SPPB), and leg press power in 100 older obese patients with HFpEF and 61 healthy controls (HCs) and adjusted for age, sex, race, and body surface area. Results Peak Vo2 (15.7 ± 0.4 ml/kg/min vs. 23.0 ± 0.6 ml/kg/min, respectively; p Conclusions In metabolic obese HFpEF, the pattern of regional adipose deposition may have important adverse consequences beyond total body adiposity. Interventions targeting intra-abdominal and intermuscular fat could potentially improve Exercise Intolerance. (Exercise Intolerance in Elderly Patients With Diastolic Heart Failure [SECRET]; NCT00959660)
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Determinants of Exercise Intolerance in patients with heart failure and reduced or preserved ejection fraction.
Journal of applied physiology (Bethesda Md. : 1985), 2015Co-Authors: Mark J. Haykowsky, Corey R. Tomczak, Jessica M. Scott, D. Ian Paterson, Dalane W. KitzmanAbstract:This mini-review summarizes the literature regarding the mechanisms of Exercise Intolerance in patients with heart failure and reduced or preserved ejection fraction (HFREF and HFPEF, respectively)...
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Sarcopenic Obesity and the Pathogenesis of Exercise Intolerance in Heart Failure With Preserved Ejection Fraction
Current heart failure reports, 2015Co-Authors: Bharathi Upadhya, Mark J. Haykowsky, Joel Eggebeen, Dalane W. KitzmanAbstract:Heart failure with preserved ejection fraction (HFpEF) is the most common form of heart failure (HF) in older adults. The primary chronic symptom in patients with HFpEF, even when well compensated, is severe Exercise Intolerance. Cardiac and peripheral functions contribute equally to Exercise Intolerance in HFpEF, though the latter has been the focus of fewer studies. Of note, multiple studies with Exercise training have shown that Exercise Intolerance can improve significantly in the absence of improvements in Exercise cardiac output, indicating a role of peripheral, noncardiac adaptations. In addition, clinical drug trials performed to date in HFpEF, all of which have focused on influencing cardiovascular function, have not been positive on primary clinical outcomes and most have not improved Exercise capacity. Mounting evidence indicates that sarcopenic obesity, characterized by the coexistence of excess fat mass and decreased muscle mass, could contribute to the pathophysiology of Exercise Intolerance in older HFpEF patients and may provide avenues for novel treatments.
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skeletal muscle abnormalities and Exercise Intolerance in older patients with heart failure and preserved ejection fraction
American Journal of Physiology-heart and Circulatory Physiology, 2014Co-Authors: Dalane W. Kitzman, Joel Eggebeen, Timothy M Morgan, Barbara J Nicklas, William E Kraus, Mary F Lyles, Mark J. HaykowskyAbstract:Heart failure (HF) with preserved ejection fraction (HFPEF) is the most common form of HF in older persons. The primary chronic symptom in HFPEF is severe Exercise Intolerance, and its pathophysiol...
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determinants of Exercise Intolerance in elderly heart failure patients with preserved ejection fraction
Journal of the American College of Cardiology, 2011Co-Authors: Mark J. Haykowsky, Peter H. Brubaker, Jerry M John, Kathryn P Stewart, Timothy M Morgan, Dalane W. KitzmanAbstract:Objectives The purpose of this study was to determine the mechanisms responsible for reduced aerobic capacity (peak V o 2 ) in patients with heart failure with preserved ejection fraction (HFPEF). Background HFPEF is the predominant form of heart failure in older persons. Exercise Intolerance is the primary symptom among patients with HFPEF and a major determinant of reduced quality of life. In contrast to patients with heart failure and reduced ejection fraction, the mechanism of Exercise Intolerance in HFPEF is less well understood. Methods Left ventricular volumes (2-dimensional echocardiography), cardiac output, V o 2 , and calculated arterial-venous oxygen content difference (A-V o 2 Diff) were measured at rest and during incremental, exhaustive upright cycle Exercise in 48 HFPEF patients (age 69 ± 6 years) and 25 healthy age-matched controls. Results In HFPEF patients compared with healthy controls, V o 2 was reduced at peak Exercise (14.3 ± 0.5 ml·kg·min −1 vs. 20.4 ± 0.6 ml·kg·min −1 ; p −1 vs. 7.6 ± 0.2 l·min −1 ; p o 2 Diff (17 ± 0.4 ml·dl −1 vs. 19 ± 0.4 ml·dl −1 , p o 2 was the change in A-V o 2 Diff from rest to peak Exercise (A-V o 2 Diff reserve) for both HFPEF patients (partial correlate, 0.58; standardized β coefficient, 0.66; p = 0.0002) and healthy controls (partial correlate, 0.61; standardized β coefficient, 0.41; p = 0.005). Conclusions Both reduced cardiac output and A-V o 2 Diff contribute significantly to the severe Exercise Intolerance in elderly HFPEF patients. The finding that A-V o 2 Diff reserve is an independent predictor of peak V o 2 suggests that peripheral, noncardiac factors are important contributors to Exercise Intolerance in these patients.
Antoni L. Andreu - One of the best experts on this subject based on the ideXlab platform.
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Muscle Signaling in Exercise Intolerance: Insights from the McArdle Mouse Model.
Medicine and science in sports and exercise, 2016Co-Authors: Carmen Fiuza-luces, Antoni L. Andreu, Gisela Nogales-gadea, Inés García-consuegra, Helios Pareja-galeano, Laura Rufián-vázquez, Laura M. Pérez, Joaquín Arenas, Miguel A. Martín, Tomàs PinósAbstract:ABSTRACTIntroductionWe recently generated a knock-in mouse model (PYGM p.R50X/p.R50X) of the McArdle disease (myophosphorylase deficiency). One mechanistic approach to unveil the molecular alterations caused by myophosphorylase deficiency, which is arguably the paradigm of “Exercise Intolerance,” is
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Mutations in mitochondrial DNA as a cause of Exercise Intolerance
Annals of Medicine, 2001Co-Authors: Salvatore Dimauro, Antoni L. AndreuAbstract:Exercise Intolerance is a common presentation of metabolic myopathies, especially of congenital errors of glycogen and lipid metabolism. Recently, however, Exercise Intolerance has been associated with specific defects in protein-coding genes of mitochondrial DNA (mtDNA), including mutations in genes for complex I, complex III, and complex IV. Contrary to the general rules of mitochondrial genetics, all patients were sporadic cases and all mutations were restricted to skeletal muscle, suggesting that they were somatic mutations not affecting the germ line.
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Exercise Intolerance resulting from a muscle-restricted mutation in the mitochondrial tRNA(Leu (CUN)) gene.
Annals of medicine, 2001Co-Authors: Cristofol Vives-bauza, Josep Gamez, Manel Roig, Paz Briones, Carles Cervera, Abelardo Solano, Julio Montoya, Antoni L. AndreuAbstract:BACKGROUND. Some patients presenting with isolated lifelong Exercise Intolerance and ragged-red fibres, harbour skeletal-muscle restricted mutations in their mitochondrial DNA.AIM. To identify the molecular defect in a patient presenting with lifelong Exercise Intolerance, ragged-red fibres and deficiencies of complexes III and IV in skeletal muscle.METHODS. The muscle biopsy was studied for activities of the respiratory chain, histochemical stains, and sequencing the tRNA genes of mitochondrial DNA.RESULTS. The patient had a heteroplasmic mutation in the tRNALeu(CUN) gene of mitochondrial DNA (G12334A). Clinical and morphological data as well as restriction fragment length polymorphism (RFLP) and single-fibre polymerase chain reaction (PCR) analyses strongly indicate that this molecular defect is the primary cause of the myopathy.CONCLUSION. Mutations in any mitochondrial gene should be considered in the differential diagnosis of patients with lifelong Exercise Intolerance, even when the neurological exa...
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Exercise Intolerance due to mutations in the cytochrome b gene of mitochondrial dna
The New England Journal of Medicine, 1999Co-Authors: Antoni L. Andreu, Michael G. Hanna, H Reichmann, Claudio Bruno, A S Penn, Kurenai Tanji, Francesco Pallotti, So Iwata, Eduardo Bonilla, Boleslaw LachAbstract:Background The mitochondrial myopathies typically affect many organ systems and are associated with mutations in mitochondrial DNA (mtDNA) that are maternally inherited. However, there is also a sporadic form of mitochondrial myopathy in which Exercise Intolerance is the predominant symptom. We studied the biochemical and molecular characteristics of this sporadic myopathy.Methods We sequenced the mtDNA cytochrome b gene in blood and muscle specimens from five patients with severe Exercise Intolerance, lactic acidosis in the resting state (in four patients), and biochemical evidence of complex III deficiency. We compared the clinical and molecular features of these patients with those previously described in four other patients with mutations in the cytochrome b gene.Results We found a total of three different nonsense mutations (G15084A, G15168A, and G15723A), one missense mutation (G14846A), and a 24-bp deletion (nucleotides 15498 to 15521) in the cytochrome b gene in the five patients. Each of these mutations impairs the enzymatic function of the cytochrome b protein. In these patients and those previously described, the clinical manifestations included progressive Exercise Intolerance, proximal limb weakness, and in some cases, attacks of myoglobinuria. There was no maternal inheritance and there were no mutations in tissues other than muscle. The absence of these findings suggests that the disorder is due to somatic mutations in myogenic stem cells after germ-layer differentiation. All the point mutations involved the substitution of adenine for guanine, but all were in different locations.Conclusions The sporadic form of mitochondrial myopathy is associated with somatic mutations in the cytochrome b gene of mtDNA. This myopathy is one cause of the common and often elusive syndrome of Exercise Intolerance. (N Engl J Med 1999; 341:1037-44.) (C)1999, Massachusetts Medical Society.
Carl J. Lavie - One of the best experts on this subject based on the ideXlab platform.
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Exercise Intolerance in Patients With Heart Failure: JACC State-of-the-Art Review.
Journal of the American College of Cardiology, 2019Co-Authors: Marco Giuseppe Del Buono, Danielle L. Kirkman, Salvatore Carbone, Ryan S. Garten, Paula Rodriguez-miguelez, Ross Arena, Barry A. Borlaug, Justin M. Canada, Marco Guazzi, Carl J. LavieAbstract:Exercise Intolerance is the cardinal symptom of heart failure (HF) and is of crucial relevance, because it is associated with a poor quality of life and increased mortality. While impaired cardiac reserve is considered to be central in HF, reduced Exercise and functional capacity are the result of key patient characteristics and multisystem dysfunction, including aging, impaired pulmonary reserve, as well as peripheral and respiratory skeletal muscle dysfunction. We herein review the different modalities to quantify Exercise Intolerance, the pathophysiology of HF, and comorbid conditions as they lead to reductions in Exercise and functional capacity, highlighting the fact that distinct causes may coexist and variably contribute to Exercise Intolerance in patients with HF.
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Exercise Intolerance in pulmonary hypertension: mechanism, evaluation and clinical implications.
Expert review of respiratory medicine, 2016Co-Authors: Abraham Samuel Babu, Ross Arena, Jonathan Myers, R Padmakumar, Arun G Maiya, Lawrence P. Cahalin, Aaron B. Waxman, Carl J. LavieAbstract:ABSTRACTIntroduction: Exercise Intolerance in pulmonary hypertension (PH) is a major factor affecting activities of daily living and quality of life. Evaluation strategies (i.e., non-invasive and invasive tests) are integral to providing a comprehensive assessment of clinical and functional status. Despite a growing body of literature on the clinical consequences of PH, there are limited studies discussing the contribution of various physiological systems to Exercise Intolerance in this patient population.Areas covered: This review, through a search of various databases, describes the physiological basis for Exercise Intolerance across the various PH etiologies, highlights the various Exercise evaluation methods and discusses the rationale for Exercise training amongst those diagnosed with PH.Expert commentary: With the growing importance of evaluating Exercise capacity in PH (class 1, Level C recommendation), understanding why Exercise performance is altered in PH is crucial. Thus, the further study is r...
Paula Rodriguez-miguelez - One of the best experts on this subject based on the ideXlab platform.
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Exercise Intolerance in Kidney Diseases: Physiological Contributors and Therapeutic Strategies.
American journal of physiology. Renal physiology, 2020Co-Authors: Danielle L. Kirkman, Natalie J. Bohmke, Salvatore Carbone, Ryan S. Garten, Paula Rodriguez-miguelez, Robert L. Franco, Jason Kidd, Antonio AbbateAbstract:Exertional fatigue, defined as the overwhelming and debilitating sense of sustained exhaustion that impacts the ability to perform activities of daily living, is highly prevalent in chronic kidney disease (CKD) and end stage renal disease (ESRD). Subjective reports of exertional fatigue are paralleled by objective measurements of Exercise Intolerance throughout the spectrum of the disease. The prevalence of Exercise Intolerance is clinically noteworthy as it leads to increased frailty, worsened quality of life and an increased risk of mortality. The physiological underpinnings of Exercise Intolerance are multifaceted and still not fully understood. This review aims to provide a comprehensive outline of the potential physiological contributors, both central and peripheral, to kidney disease related Exercise Intolerance and highlight current and prospective interventions to target this symptom. In this review the kidney disease-related metabolic derangements, cardiac and pulmonary dysfunction, altered physiologic responses to oxygen consumption, vascular derangements and sarcopenia are discussed in the context of Exercise Intolerance. Lifestyle interventions to improve exertional fatigue, such as aerobic and resistance Exercise training, are discussed and the lack of dietary interventions to improve Exercise tolerance is highlighted. Current and prospective pharmaceutical and nutraceutical strategies to improve exertional fatigue are also broached. An extensive understanding of the pathophysiological mechanisms of Exercise Intolerance will allow for the development of more targeted therapeutic approached to improve exertional fatigue and health related quality of life in CKD and ESRD.
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Exercise Intolerance in Cystic Fibrosis: Importance of Skeletal Muscle.
Medicine and science in sports and exercise, 2020Co-Authors: Paula Rodriguez-miguelez, Nichole Seigler, Haruki Ishii, Reva Crandall, Kathleen T. Mckie, Caralee Forseen, Ryan A. HarrisAbstract:PURPOSE Exercise Intolerance, evaluated by O2 consumption, predicts mortality in Cystic Fibrosis (CF). People with CF exhibit skeletal muscle dysfunctions that may contribute to an imbalance between O2 delivery and utilization. Sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, increases blood flow and improves O2 consumption, although the exact mechanisms in CF have yet to be elucidated. Thus, we hypothesized that Exercise Intolerance in CF is limited primarily by an impaired skeletal muscle O2 utilization, and sildenafil improves Exercise tolerance in CF by addressing this mismatch between O2 demand and extraction. METHODS Fifteen individuals with mild-to-moderate CF and eighteen healthy controls completed an incremental Exercise test and measurements of gaseous exchange, chronotropic response, hemodynamics, and O2 extraction and utilization. People with CF also completed a four-week-treatment with sildenafil with a subsequent follow-up evaluation after treatment. RESULTS Skeletal muscle O2 extraction and utilization during Exercise were reduced in people with CF when compared to controls. Exercise capacity in our CF population was minimally limited by hemodynamic or chronotopic responses, while peripheral O2 extraction was more closely associated with Exercise capacity. The study also demonstrated that four weeks of sildenafil improved skeletal muscle O2 utilization during Exercise to similar values observed in healthy individuals. CONCLUSIONS Individuals with mild to moderate CF exhibit Exercise Intolerance secondary to a reduction in O2 utilization by the exercising skeletal muscle. The present study demonstrated that four weeks of sildenafil treatment improves the capacity of the skeletal muscle to utilize O2 more efficiently during Exercise. Findings from the present study highlight the importance of targeting skeletal muscle O2 utilization to improve Exercise tolerance in CF.
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Exercise Intolerance in Patients With Heart Failure: JACC State-of-the-Art Review.
Journal of the American College of Cardiology, 2019Co-Authors: Marco Giuseppe Del Buono, Danielle L. Kirkman, Salvatore Carbone, Ryan S. Garten, Paula Rodriguez-miguelez, Ross Arena, Barry A. Borlaug, Justin M. Canada, Marco Guazzi, Carl J. LavieAbstract:Exercise Intolerance is the cardinal symptom of heart failure (HF) and is of crucial relevance, because it is associated with a poor quality of life and increased mortality. While impaired cardiac reserve is considered to be central in HF, reduced Exercise and functional capacity are the result of key patient characteristics and multisystem dysfunction, including aging, impaired pulmonary reserve, as well as peripheral and respiratory skeletal muscle dysfunction. We herein review the different modalities to quantify Exercise Intolerance, the pathophysiology of HF, and comorbid conditions as they lead to reductions in Exercise and functional capacity, highlighting the fact that distinct causes may coexist and variably contribute to Exercise Intolerance in patients with HF.