The pathophysiology of heart failure with preserved ejection fraction: From molecular mechanisms to exercise haemodynamics (original) (raw)
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Heart Failure With Preserved Ejection Fraction: A Review of Cardiac and Noncardiac Pathophysiology
Frontiers in Physiology, 2019
Heart failure with preserved ejection fraction (HFpEF) is one of the largest unmet clinical needs in 21st-century cardiology. It is a complex disorder resulting from the influence of several comorbidities on the endothelium. A derangement in nitric oxide bioavailability leads to an intricate web of physiological abnormalities in the heart, blood vessels, and other organs. In this review, we examine the contribution of cardiac and noncardiac factors to the development of HFpEF. We zoom in on recent insights on the role of comorbidities and microRNAs in HFpEF. Finally, we address the potential of exercise training, which is currently the only available therapy to improve aerobic capacity and quality of life in HFpEF patients. Unraveling the underlying mechanisms responsible for this improvement could lead to new biomarkers and therapeutic targets for HFpEF.
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.
Haemodynamics of Heart Failure With Preserved Ejection Fraction: A Clinical Perspective
Cardiac Failure Review, 2016
Despite the burden of heart failure (HF) with preserved ejection fraction (HFpEF), 1 its pathophysiological mechanisms remain controversial and are likely to be multifactorial. 2,3,4 The lack of a comprehensive paradigm applicable to all patients suggests that haemodynamic derangements responsible for this disorder may be quite heterogeneous. As recently highlighted, haemodynamic features of HFpEF involve both cardiac and extra-cardiac mechanisms. Studies on HFpEF have shown diastolic abnormalities, subtle systolic dysfunction, pulmonary hypertension, right ventricular dysfunction and chronotropic incompetence, in addition to ventricular-vascular mechanisms and abdominal factors. In this short review we highlight and discuss the different mechanisms characterizing HFpEF haemodynamics, which finally lead to elevated left ventricular end diastolic pressure (LVEDP), a common hallmark of this multifaceted syndrome (see Figure 1).
Journal of The American College of Cardiology, 2009
We sought to evaluate the role of exercise-related changes in left ventricular (LV) relaxation and of LV contractile function and vasculoventricular coupling (VVC) in the pathophysiology of heart failure with preserved ejection fraction (HFpEF) and to assess myocardial energetic status in these patients.To date, no studies have investigated exercise-related changes in LV relaxation and VVC as well as in vivo myocardial energetic status in patients with HFpEF.We studied 37 patients with HFpEF and 20 control subjects. The VVC and time to peak LV filling (nTTPF, a measure of LV active relaxation) were assessed while patients were at rest and during exercise by the use of radionuclide ventriculography. Cardiac energetic status (creatine phosphate/adenosine triphosphate ratio) was assessed by the use of 31P magnetic resonance spectroscopy at 3-T.When patients were at rest, nTTPF and VVC were similar in patients with HFpEF and control subjects. The cardiac creatine phosphate/adenosine triphosphate ratio was reduced in patients with HFpEF versus control subjects (1.57 ± 0.52 vs. 2.14 ± 0.63; p = 0.003), indicating reduced energy reserves. Peak maximal oxygen uptake and the increase in heart rate during maximal exercise were lower in patients with HFpEF versus control subjects (19 ± 4 ml/kg/min vs. 36 ± 8 ml/kg/min, p < 0.001, and 52 ± 16 beats/min vs. 81 ± 14 beats/min, p < 0.001). The relative changes in stroke volume and cardiac output during submaximal exercise were lower in patients with HFpEF versus control subjects (ratio exercise/rest: 0.99 ± 0.34 vs. 1.25 ± 0.47, p = 0.04, and 1.36 ± 0.45 vs. 2.13 ± 0.72, p < 0.001). The nTTPF decreased during exercise in control subjects but increased in patients with HFpEF (−0.03 ± 12 s vs. +0.07 ± 0.11 s; p = 0.005). The VVC decreased on exercise in control subjects but was unchanged in patients with HFpEF (−0.01 ± 0.15 vs. −0.25 ± 0.19; p < 0.001).Patients with HFpEF have reduced cardiac energetic reserve that may underlie marked dynamic slowing of LV active relaxation and abnormal VVC during exercise.
Heart Failure with Preserved Ejection Fraction—a Concise Review
2020
Purpose of Review Heart failure with preserved ejection fraction (HFpEF) is a relatively new disease entity used in medical terminology; however, both the number of patients and its clinical significance are growing. HFpEF used to be seen as a mild condition; however, the symptoms and quality of life of the patients are comparable to those with reduced ejection fraction. The disease is much more complex than previously thought. In this article, information surrounding the etiology, diagnosis, prognosis, and possible therapeutic options of HFpEF are reviewed and summarized. Recent Findings It has recently been proposed that heart failure (HF) is rather a heterogeneous syndrome with a spectrum of overlapping and distinct characteristics. HFpEF itself can be distilled into different phenotypes based on the underlying biology. The etiological factors of HFpEF are unclear; however, systemic low-grade inflammation and microvascular damage as a consequence of comorbidities associated with ...
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...