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Advances in Diagnosis and Management of Heart Failure with Preserved Ejection Fraction

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Cardiology".

Deadline for manuscript submissions: closed (15 January 2024) | Viewed by 3402

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Special Issue Editor

Dr. Bharathi Upadhya

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Guest Editor

Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA
Interests: HFpEF; cardiac imaging; adult congenital heart disease; echocardiography; hypertensive heart disease

Special Issue Information

Dear Colleagues,

Heart failure (HF) with preserved ejection fraction (HFpEF) is the most common form of HF in older adults. HFpEF is associated with a high morbidity and mortality. After being hospitalized for HF, the 5-year survival of HFpEF is a dismal 35%, which is worse than many cancers. Despite this, there are currently few effective therapies for HFpEF. Most approved therapies for HF with reduced ejection fraction (HFrEF) have been proven ineffective for HFpEF, suggesting significant differences in the fundamental pathophysiology and therapeutic targets of HFpEF compared to HFrEF. HFpEF was initially viewed as a disorder due to left ventricular diastolic function abnormalities. However, our understanding has evolved, and multiple cardiac and noncardiac abnormalities are now well-known, including left ventricular systolic dysfunction, left atrial dysfunction, right ventricular dysfunction, pulmonary hypertension, and pulmonary vascular disease, arterial stiffness, ventricular–vascular stiffening, coronary and peripheral microvascular dysfunction, enhanced pericardial restraint, skeletal muscle dysfunction, and pulmonary abnormalities. An evolving paradigm suggests that HFpEF is a systemic syndrome involving multiple organ systems, likely triggered by inflammation and important contributions from aging and obesity. HFpEF includes multifactorial pathophysiology, frequent multiple chronic comorbidities, and multiorgan involvement. Due to its heterogeneity, a "one-size-fits-all" strategy is unlikely to work in cases of HFpEF. In addition, much broader research into myocardial and non-myocardial abnormalities at a tissue level in carefully phenotyped HFpEF subgroups is needed. Efforts are underway to utilize machine learning techniques to identify novel therapeutic targets, improve future clinical trials’ design, and develop practical clinical management algorithms. Finally, the complexities of this disease means that patients are demanding a more holistic approach by addressing not only direct HF-related outcomes but also optimal management, with particular focus on their quality of life. In this Special Issue, we aim to recruit prospective researchers that describe and share their scientific clinical advances, which help us to understand and treat this highly prevalent, heterogeneous clinical syndrome, whether in original investigations, narrative reviews, systematic reviews and meta-analyses.

Dr. Bharathi Upadhya
Guest Editor

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Keywords

heart failure
preserved ejection fraction
aging
obesity
systemic syndrome
comorbidities
therapy

Published Papers (3 papers)

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Research

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13 pages, 1358 KiB

Open AccessArticle

Clinical Trajectory and Risk Stratification for Heart Failure with Preserved Ejection Fraction in a Real-World Cohort of Patients with Suspected Coronary Artery Disease

by Guglielmo Gioia, Karl-Patrik Kresoja, Sebastian Rosch, Anne Schöber, Elias Harnisch, Maximilian von Roeder, Markus Scholz, Sylvia Henger, Berend Isermann, Holger Thiele, Philipp Lurz and Karl-Philipp Rommel

J. Clin. Med. 2024, 13(7), 2092; https://doi.org/10.3390/jcm13072092 - 3 Apr 2024

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Abstract

Background: Heart failure with preserved ejection fraction (HFpEF) is a widespread condition with significant morbidity and mortality. Its clinical heterogeneity may delay the diagnosis. Aim: To identify predictors of HFpEF-related hospitalizations in ambulatory patients presenting with elevated cardiovascular risk, suspected coronary artery diseases (CADs), and positive HFpEF screenings. Methods: Consecutive patients presenting with suspected CAD, enrolled in the observational LIFE-Heart study (2006–2014, NCT00497887), and meeting HFpEF criteria per the 2016 European Society of Cardiology (ESC) guidelines were categorized according to the presence of “overlapping conditions” potentially masking or contributing to their symptoms. Additional stratification using the H₂FPEF score (<2: low risk, 2–5: intermediate risk, and ≥6 high risk) was performed. Follow-up for hospitalizations, reasons of hospitalization, and death spanned a median of 6 years. Results: Of 1054 patients (66 ± 10 years, 60% male, NT-pro-BNP 286, IQR 183–574 pg/mL), 53% had overlapping conditions, while 47% had “isolated HFpEF”. The H₂FPEF scores classified 23%, 57%, and 20% as low-, intermediate-, and high-risk, respectively, with consistent proportions across patients with and without overlapping conditions (p = 0.91). During the follow-up observational phase, 54% were rehospitalized, 22% experienced heart failure (HF) rehospitalizations, and 11% of patients died. Multivariable logistic regression revealed a high-risk H₂FPEF category as an independent predictor of HF rehospitalization in the overall cohort (odds ratio: 3.4, CI: 2.4–4.9, p < 0.01) as well as in patients with and without overlapping conditions. Furthermore, a H₂FPEF score ≥ 6 was independently associated with higher mortality rates (hazard ratio: 1.8, CI: 1.2–2.6, p < 0.01) in the Cox regression analysis. Conclusions: Ambulatory patients presenting for suspected CAD and meeting HFpEF screening criteria face elevated risks for rehospitalizations over six years. Regardless of concomitant diagnoses, quantifying cardiac damage with the H₂FPEF score helps in risk-stratifying patients for HF hospitalization and mortality. Full article

(This article belongs to the Special Issue Advances in Diagnosis and Management of Heart Failure with Preserved Ejection Fraction)

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Review

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17 pages, 815 KiB

Open AccessReview

Myocardial Metabolism in Heart Failure with Preserved Ejection Fraction

by John Aaron Henry, Liam S. Couch and Oliver J. Rider

J. Clin. Med. 2024, 13(5), 1195; https://doi.org/10.3390/jcm13051195 - 20 Feb 2024

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Abstract

Heart failure with preserved ejection fraction (HFpEF) is increasingly prevalent and now accounts for half of all heart failure cases. This rise is largely attributed to growing rates of obesity, hypertension, and diabetes. Despite its prevalence, the pathophysiological mechanisms of HFpEF are not fully understood. The heart, being the most energy-demanding organ, appears to have a compromised bioenergetic capacity in heart failure, affecting all phenotypes and aetiologies. While metabolic disturbances in heart failure with reduced ejection fraction (HFrEF) have been extensively studied, similar insights into HFpEF are limited. This review collates evidence from both animal and human studies, highlighting metabolic dysregulations associated with HFpEF and its risk factors, such as obesity, hypertension, and diabetes. We discuss how changes in substrate utilisation, oxidative phosphorylation, and energy transport contribute to HFpEF. By delving into these pathological shifts in myocardial energy production, we aim to reveal novel therapeutic opportunities. Potential strategies include modulating energy substrates, improving metabolic efficiency, and enhancing critical metabolic pathways. Understanding these aspects could be key to developing more effective treatments for HFpEF. Full article

(This article belongs to the Special Issue Advances in Diagnosis and Management of Heart Failure with Preserved Ejection Fraction)

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Graphical abstract

10 pages, 1573 KiB

Open AccessReview

Targeting Collagen Pathways as an HFpEF Therapeutic Strategy

by Alice Bonanni, Ramona Vinci, Alessia d’Aiello, Maria Chiara Grimaldi, Marianna Di Sario, Dalila Tarquini, Luca Proto, Anna Severino, Daniela Pedicino and Giovanna Liuzzo

J. Clin. Med. 2023, 12(18), 5862; https://doi.org/10.3390/jcm12185862 - 9 Sep 2023

Viewed by 1052

Abstract

Heart failure with preserved ejection fraction (HFpEF) is a complex and heterogeneous clinical syndrome. The prevalence is expected to increase in the coming years, resulting in heart failure with reduced ejection fraction (HFrEF). This condition poses a burden to the global health care system as the number of patients affected by this condition is constantly increasing due to a rising average lifespan. The absence of validated drugs effective in reducing hospitalization rates and mortality may reflect the impossibility of applying a one size fits all approach as in HFrEF, heading for a personalized approach. Available evidence demonstrated the link between collagen quantity and quality alterations, and cardiac remodeling. In the context of fibrosis, collagen cross-linking is strictly involved, displaying two types of mechanisms: enzymatic and non-enzymatic. In the murine model, enzymatic inhibition of fibrosis-inducing protease-activated receptor-1 (PAR1) and transforming growth factor (TGF)-β signaling appeared to reduce cardiac fibrosis. On the other hand, in the case of non-enzymatic cross-linking, sodium glucose co-transporter type 2 inhibitors (SGLT2is), appeared to counteract the deposition of advanced glycation end-products (AGEs), which in turn contributed to ventricular remodeling. In this review, we address the mechanisms associated with collagen alterations to identify potential targets of cardiac fibrosis in HFpEF patients. Full article

(This article belongs to the Special Issue Advances in Diagnosis and Management of Heart Failure with Preserved Ejection Fraction)

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