Phenotype-Specific Treatment of Heart Failure With Preserved Ejection Fraction A Multiorgan Roadmap
Sanjiv J. Shah,Dalane W. Kitzman,Barry A. Borlaug,Loek van Heerebeek,Michael R. Zile,David A. Kass,Walter Paulus +6 more
TLDR
Personalized therapeutic strategies are proposed that addresses HFpEF-specific signaling and phenotypic diversity and target individual steps of systemic and myocardial signaling cascades.Abstract:
Heart failure (HF) with preserved ejection fraction (EF; HFpEF) accounts for 50% of HF cases, and its prevalence relative to HF with reduced EF continues to rise. In contrast to HF with reduced EF, 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, an HFpEF treatment strategy is proposed that addresses HFpEF-specific signaling and phenotypic diversity. In HFpEF, extracardiac comorbidities such as metabolic risk, arterial hypertension, and renal insufficiency drive left ventricular remodeling and dysfunction through systemic inflammation and coronary microvascular endothelial dysfunction. The latter affects left ventricular 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 and cyclic guanosine monophosphate. 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 5 inhibitors, muscle weakness by exercise training, sodium retention by diuretics and monitoring devices, myocardial nitric oxide bioavailability by inorganic nitrate-nitrite, myocardial cyclic guanosine monophosphate content by neprilysin or phosphodiesterase 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.read more
Citations
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Journal ArticleDOI
Epidemiology of heart failure with preserved ejection fraction
TL;DR: The current knowledge regarding the epidemiology ofHFpEF is summarized with a focus on community-based studies relevant to quantifying the population burden of HFpEF, and current data regarding the prevalence and incidence in the community are presented.
Journal ArticleDOI
Sedentary Behavior, Exercise, and Cardiovascular Health.
TL;DR: The prognostic utility of cardiorespiratory fitness compared with obesity and the metabolic syndrome is reviewed, as well as the increase of physical activity /ET for patients with heart failure as a therapeutic strategy, and ET dosing.
Journal ArticleDOI
Evidence Supporting the Existence of a Distinct Obese Phenotype of Heart Failure with Preserved Ejection Fraction
TL;DR: Obesity-related HFpEF is a genuine form of cardiac failure and a clinically relevant phenotype that may require specific treatments, and is a viable candidate for phenotyping.
Journal ArticleDOI
Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology.
Steven J. Forrester,George W. Booz,Curt D. Sigmund,Thomas M. Coffman,Tatsuo Kawai,Victor Rizzo,Rosario Scalia,Satoru Eguchi +7 more
TL;DR: It is expected that rigorous translational research of the ANG II signaling pathways including those in large animals and humans will contribute to establishing effective new therapies against various diseases.
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Artificial Intelligence in Cardiology
Kipp W. Johnson,Jessica Torres Soto,Benjamin S. Glicksberg,Khader Shameer,Riccardo Miotto,Mohsin Ali,Euan A. Ashley,Joel T. Dudley,Joel T. Dudley +8 more
TL;DR: This paper reviews predictive modeling concepts relevant to cardiology such as feature selection and frequent pitfalls such as improper dichotomization, and describes the advent of deep learning and related methods collectively called unsupervised learning, which could be applied to enable precision cardiology and improve patient outcomes.
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A Novel Paradigm for Heart Failure With Preserved Ejection Fraction: Comorbidities Drive Myocardial Dysfunction and Remodeling Through Coronary Microvascular Endothelial Inflammation
Walter Paulus,Carsten Tschöpe +1 more
TL;DR: In this article, a new paradigm for heart failure with preserved ejection fraction (HFPEF) development is proposed, which identifies a systemic proinflammatory state induced by comorbidities as the cause of myocardial structural and functional alterations.
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Spironolactone for Heart Failure with Preserved Ejection Fraction
Bertram Pitt,Marc A. Pfeffer,Susan F. Assmann,Robin Boineau,Inder S. Anand,Brian Claggett,Nadine Oliveira Clausell,Akshay S. Desai,Rafael Diaz,Jerome L. Fleg,Ivan Gordeev,Brian Harty,John F. Heitner,Christopher T. Kenwood,Eldrin F. Lewis,Eileen O'Meara,Jeffrey L. Probstfield,Tamaz Shaburishvili,Sanjiv J. Shah,Scott D. Solomon,Nancy K. Sweitzer,Song Yang,Sonja M. McKinlay +22 more
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