Epidemiology of Heart Failure with Preserved Ejection Fraction

Dhingra, Abhinav; Garg, Aayushi; Kaur, Simrat; Chopra, Sakshi; Batra, Jaspreet S.; Pandey, Ambarish; Chaanine, Antoine H.; Agarwal, Sunil

doi:10.1007/s11897-014-0223-7

Cited by 100 publications

(80 citation statements)

References 89 publications

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“…Large outcome trials and registries all revealed HFpEF patients to be of advanced age and predominantly women and to suffer from multiple comorbidities such as overweight/obesity (84%) 15 , arterial hypertension (60-80%) 16 , type 2 diabetes mellitus (20-45%) 16 , renal insufficiency and sleep apnea. Aging and the aforementioned comorbidities may initiate chronic systemic inflammation as manifest from biomarker profiles which revealed high plasma levels of soluble interleukin 1 receptor-like 1 (IL1RL1), C-reactive protein (CRP) and growth differentiation factor 15 (GDF15) in HFpEF 17-20 .…”

Section: Systemic and Myocardial Signallingmentioning

confidence: 99%

Phenotype-Specific Treatment of Heart Failure With Preserved Ejection Fraction

Shah¹,

et al. 2016

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Heart failure (HF) with preserved ejection fraction (EF) (HFpEF) accounts for 50% of HF cases and its prevalence relative to HF with reduced EF (HFrEF) continues to rise. In contrast to HFrEF, large trials testing neurohumoral inhibition in HFpEF failed to reach a positive outcome. This failure was recently attributed to distinct systemic and myocardial signaling in HFpEF and to diversity of HFpEF phenotypes. In this review, a HFpEF treatment strategy is proposed which addresses HFpEF-specific signaling and phenotypic diversity. In HFpEF, extracardiac comorbidities such as metabolic risk, arterial hypertension and renal insufficiency drive left ventricular (LV) remodeling and dysfunction through systemic inflammation and coronary microvascular endothelial dysfunction. The latter affects LV diastolic dysfunction through macrophage infiltration resulting in interstitial fibrosis and through altered paracrine signaling to cardiomyocytes, which become hypertrophied and stiff because of low nitric oxide (NO) and cyclic guanosine monophosphate (cGMP). Systemic inflammation also affects other organs such as lungs, skeletal muscle and kidneys leading respectively to pulmonary hypertension, muscle weakness and sodium retention. Individual steps of these signaling cascades can be targeted by specific interventions: metabolic risk by caloric restriction, systemic inflammation by statins, pulmonary hypertension by phosphodiesterase (PDE) 5 inhibitors, muscle weakness by exercise training, sodium retention by diuretics and monitoring devices, myocardial NO bioavailability by inorganic nitrate-nitrite, myocardial cGMP content by neprilysin or PDE 9 inhibition and myocardial fibrosis by spironolactone. Because of phenotypic diversity in HFpEF, personalized therapeutic strategies are proposed, which are configured in a matrix with HFpEF presentations in the abscissa and HFpEF predispositions in the ordinate.

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Section: Systemic and Myocardial Signallingmentioning

confidence: 99%

Phenotype-Specific Treatment of Heart Failure With Preserved Ejection Fraction

Shah¹,

et al. 2016

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“…Heart failure is typically divided into two phenotypes, heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). More than half of newly diagnosed heart failure patients present with preserved ejection fraction [5, 6]. Standard of care medications for HFrEF have long been established, but thus far, large clinical trials have failed to show any significant benefit in life expectancy in patients with HFpEF [7].…”

Section: Introductionmentioning

confidence: 99%

Endothelial specific SIRT3 deletion impairs glycolysis and angiogenesis and causes diastolic dysfunction

Zeng

Chen

et al. 2017

Journal of Molecular and Cellular Cardiology

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Endothelial glycolysis plays a critical role in the regulation of angiogenesis. We investigated the role of Sirtuin 3 (SIRT3) on endothelial cell (EC) glycolytic metabolism, angiogenesis, and diastolic function. Our aim was to test the hypothesis that loss of SIRT3 in ECs impairs endothelial glycolytic metabolism and angiogenesis and contributes to myocardial capillary rarefaction and the development of diastolic dysfunction. Using SIRT3 deficient ECs, SIRT3 was found to regulate a metabolic switch between mitochondrial respiration and glycolysis. SIRT3 knockout (KO)-ECs exhibited higher mitochondrial respiration and reactive oxygen species (ROS) formation. SIRT3 knockout (KO)-ECs exhibited a reduction in the expression of glycolytic enzyme, PFKFB3, and a fall in glycolysis and angiogenesis. Blockade of PFKFB3 reduced glycolysis and downregulated expression of VEGF and Angiopoietin-1 (Ang-1) in ECs. Deletion of SIRT3 in ECs also impaired hypoxia-induced expression of HIF-2α, VEGF, and Ang-1, as well as reduced angiogenesis. In vivo, endothelial-specific SIRT3 KO (ECKO) mice exhibited a myocardial capillary rarefaction together with a reduced coronary flow reserve (CFR) and diastolic dysfunction. Histologic study further demonstrated that knockout of SIRT3 in ECs significantly increased perivascular fibrosis in the coronary artery. These results implicate a role of SIRT3 in modulating endothelial function and cardiac function. Ablation of SIRT3 leads to impairment of EC glycolytic metabolism and angiogenic signaling, which may contribute to coronary microvascular rarefaction and diastolic dysfunction in SIRT3 ECKO mice.

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“…1 HFpEF is associated with high morbidity and mortality, and no evidence-based therapies are available for these patients. 2 Increased pulmonary arterial pressure is another important factor that is associated with the severity of HFpEF and consequently results in higher mortality.…”

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confidence: 99%

Clinical and Hemodynamic Correlates and Prognostic Value of VE/VCO 2 Slope in Patients With Heart Failure With Preserved Ejection Fraction and Pulmonary Hypertension

Klaassen

Liu

Hummel

et al. 2017

Journal of Cardiac Failure

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Background: Impaired exercise capacity is one of the hallmarks of heart failure with preserved ejection fraction (HFpEF), but the clinical and hemodynamic correlates and prognostic value of exercise testing in patients with HFpEF is unknown. Methods: Patients with HFpEF (left ventricular ejection fraction [LVEF] ≥45%) and pulmonary hypertension underwent cardiopulmonary exercise test (CPX) to measure maximal (peak VO2) and submaximal (ventilatory equivalent for carbon dioxide [VE/VCO2] slope) exercise capacity. In addition, right heart catheterization was performed. Patients were grouped in tertiles based on the VE/VCO2 slope. Univariate and multivariate regression analyses were performed. A Cox regression analysis was performed to determine the mortality during follow-up. Results: We studied 88 patients: mean age 73 ± 9 years, 67% female, mean LVEF 58%, median N-terminal pro-B-type natriuretic peptide (NT-proBNP) 840 (interquartile range 411-1938) ng/L. Patients in the highest VE/VCO2 tertile had the most severe HF, as reflected in higher New York Heart Association functional class and higher NT-proBNP plasma levels (all P < .05 for trend), whereas LVEF was similar between the groups. Multivariable regression analysis with backward elimination on invasive hemodynamic measurements showed that VE/VCO2 slope was independently associated with pulmonary vascular resistance (PVR). Cox regression analysis showed that increased VE/VCO2 slope (but not peak VO2) was independently associated with increased mortality. Conclusion: Increased VE/VCO2 slope was associated with more severe disease and higher PVR and was independently associated with increased mortality in patients with HFpEF. (J Cardiac Fail 2017;23:777-782) Key Words: VE/VCO2 slope, heart failure with preserved ejection fraction, cardiopulmonary exercise test.

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Epidemiology of Heart Failure with Preserved Ejection Fraction

Cited by 100 publications

References 89 publications

Phenotype-Specific Treatment of Heart Failure With Preserved Ejection Fraction

Phenotype-Specific Treatment of Heart Failure With Preserved Ejection Fraction

Endothelial specific SIRT3 deletion impairs glycolysis and angiogenesis and causes diastolic dysfunction

Clinical and Hemodynamic Correlates and Prognostic Value of VE/VCO 2 Slope in Patients With Heart Failure With Preserved Ejection Fraction and Pulmonary Hypertension

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