Invited editorial commentary for American Heart Journal mechanisms of exercise training in heart failure with preserved ejection fraction: Central disappointment and peripheral promise (original) (raw)
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Journal of Cardiopulmonary Rehabilitation and Prevention, 2020
H eart failure (HF) is a major health care problem associated with high morbidity and mortality. 1 Currently, >6 million Americans ≥20 y of age have HF, and its prevalence is expected to increase by 46% by 2030. 1,2 Nearly half of all HF patients have preserved left ventricular (LV) ejection fraction (heart failure with preserved ejection fraction [HF-pEF]) and this phenotype is more common in older individuals, women, and those with a history of hypertension, obesity, and anemia. 1,3 Decreased exercise tolerance is a hallmark feature in clinically stable HFpEF patients and is associated with reduced quality of life (QoL). 4,5 Given the relationship between cardiorespiratory fitness (CRF; ie, peak oxygen uptake, • Vo 2peak) and survival, 6,7 an important goal of therapy should be to improve CRF in HFpEF patients. 8-12 Currently, exercise training is the only proven effective intervention to improve • Vo 2peak , aerobic endurance, and QoL in HFpEF patients. 4,10 Several recent meta-analyses have reported that endurance exercise training, performed alone or combined with resistance training, improves • Vo 2peak and 6-min walk test distance by 2.2 mL/kg/min and 33 m, respectively. 4,13,14 Accordingly, understanding the mechanisms responsible for reduced • Vo 2peak and its improvement with exercise training is critical to optimally improve functional capacity and QoL in HFpEF patients. In this brief review, the pathophysiology of exercise intolerance and the role of exercise training to improve • Vo 2peak in clinically stable patients with HFpEF are discussed. Further discussion of the mechanisms responsible for the exercise training-mediated increase in • Vo 2peak is provided, along with evidence-based exercise prescription guidelines for clinically stable HFpEF patients participating in an exercise-based cardiac rehabilitation (CR) program. PATHOPHYSIOLOGY OF EXERCISE INTOLERANCE IN HFpEF Appreciating the Fick principle for • Vo 2 is fundamental to understanding the pathophysiology of exercise intolerance in patients with HFpEF. Specifically, the Fick principle dictates that • Vo 2 = cardiac output (Q) × arterial-venous O 2 content difference (a-vO 2 Diff), with Q and the a-vO 2 Diff each having their own modulating factors that ultimately drive the highest achievable • Vo 2 at peak exercise (Figure). ROLE OF CARDIAC FUNCTION ON EXERCISE LIMITATIONS IN HFpEF The reduction in • Vo 2peak observed in patients with HFpEF is due, in part, to a reduction in cardiac function during exercise. Several independent laboratories have demonstrated that peak Q is 30-40% lower in patients with HF-pEF compared with control subjects. 16-19 Evidence to date suggests that chronotropic incompetence rather than stroke volume (SV) is a fundamental concern for the blunted Q response to peak exercise in patients with HFpEF. 16-18,20-22 Indeed, significant relationships between Q (independent of major reductions in SV) 18 and heart rate (HR) 20 with • Vo 2peak have previously been reported, even when matched for important comorbidities, 21 supporting that underlying chronotropic incompetence is a major contributor to reduced Q and subsequent reductions in • Vo 2peak in HFpEF. Despite the major role that HR plays on the severely reduced peak exercise • Vo 2 in patients with HFpEF, several impairments in left ventricular function have also been reported (Figure). Normally, LV relaxation is augmented during exercise to compensate for the reduction in filling
Journal of Clinical Exercise Physiology, 2020
Heart failure with preserved ejection fraction (HFpEF) accounts for approximately 50% of all heart failure (HF) cases and is the fastest growing form of HF in the United States. The cornerstone symptom of clinically stable HFpEF is severe exercise intolerance (defined as reduced peak exercise oxygen uptake, VO2peak) secondary to central and peripheral abnormalities that result in reduced oxygen delivery to and/or use by exercising skeletal muscle. To date, pharmacotherapy has not been shown to improve VO2peak, quality of life, and survival in patients with HFpEF. In contrast, exercise training is currently the only efficacious treatment strategy to improve VO2peak, aerobic endurance, and quality of life in patients with HFpEF. In this updated review, we discuss the specific central and peripheral mechanisms that are responsible for the impaired exercise responses as well as the role of exercise training to improve VO2peak in clinically stable patients with HFpEF. We also discuss the...
Exercise intolerance in heart failure with preserved ejection fraction: more than a heart problem
Journal of geriatric cardiology : JGC, 2015
Heart failure (HF) with preserved ejection fraction (HFpEF) is the most common form of HF in older adults, and is increasing in prevalence as the population ages. Furthermore, HFpEF is increasing out of proportion to HF with reduced EF (HFrEF), and its prognosis is worsening while that of HFrEF is improving. Despite the importance of HFpEF, our understanding of its pathophysiology is incomplete, and optimal treatment remains largely undefined. A cardinal feature of HFpEF is reduced exercise tolerance, which correlates with symptoms as well as reduced quality of life. The traditional concepts of exercise limitations have focused on central dysfunction related to poor cardiac pump function. However, the mechanisms are not exclusive to the heart and lungs, and the understanding of the pathophysiology of this disease has evolved. Substantial attention has focused on defining the central versus peripheral mechanisms underlying the reduced functional capacity and exercise tolerance among ...
Circulation, 2019
Background: Heart failure with preserved ejection fraction (HFpEF) is common, yet there is currently no consensus on how to define HFpEF according to various society and clinical trial criteria. How clinical and hemodynamic profiles of patients vary across definitions is unclear. We sought to determine clinical characteristics, as well as physiologic and prognostic implications of applying various criteria to define HFpEF. Methods: We examined consecutive patients with chronic exertional dyspnea (New York Heart Association class II to IV) and ejection fraction ≥50% referred for comprehensive cardiopulmonary exercise testing with invasive hemodynamic monitoring. We applied societal and clinical trial HFpEF definitions and compared clinical profiles, exercise responses, and cardiovascular outcomes. Results: Of 461 patients (age 58±15 years, 62% women), 416 met American College of Cardiology/American Heart Association (ACC/AHA), 205 met European Society of Cardiology (ESC), and 55 met ...
Abnormal haemodynamic response to exercise in heart failure with preserved ejection fraction
European Journal of Heart Failure, 2011
Peak oxygen uptake (VO 2) is diminished in patients with heart failure with preserved ejection fraction (HFpEF) suggesting impaired cardiac reserve. To test this hypothesis, we assessed the haemodynamic response to exercise in HFpEF patients. Methods and results Eleven HFpEF patients (73 + 7 years, 7 females/4 males) and 13 healthy controls (70 + 4 years, 6 females/7 males) were studied during submaximal and maximal exercise. The cardiac output (Q c , acetylene rebreathing) response to exercise was determined from linear regression of Q c and VO 2 (Douglas bags) at rest, 30% and 60% of peak VO 2 , and maximal exercise. Peak VO 2 was lower in HFpEF patients than in controls (13.7 + 3.4 vs. 21.6 + 3.6 mL/kg/min; P , 0.001), while indices of cardiac reserve were not statistically different: peak cardiac power output [CPO ¼ Q c × mean arterial pressure (MAP); HFpEF 1790 + 509 vs. controls 2119 + 581 L/mmHg/min; P ¼ 0.20]; peak stroke work [SW ¼ stroke volume (SV) × MAP; HFpEF 13 429 + 2269 vs. controls 13 200 + 3610 mL/mmHg; P ¼ 0.80]. The DQ c /DVO 2 slope was abnormally elevated in HFpEF patients vs. controls (11.2 +3.6 vs. 8.3 + 1.5; P ¼ 0.015). Conclusion Contrary to our hypothesis, cardiac reserve is not significantly impaired in well-compensated outpatients with HFpEF. The abnormal haemodynamic response to exercise (decreased peak VO 2 , increased DQ c /DVO 2 slope) is similar to that observed in patients with mitochondrial myopathies, suggesting an element of impaired skeletal muscle oxidative metabolism. This impairment may limit functional capacity by two mechanisms: (i) premature skeletal muscle fatigue and (ii) metabolic signals to increase the cardiac output response to exercise which may be poorly tolerated by a left ventricle with impaired diastolic function.