Endothelin 1 Is Associated with Heart Failure Hospitalization and Long-Term Mortality in Patients with Heart Failure with Preserved Ejection Fraction and Pulmonary Hypertension

Cardiology ◽  
2019 ◽  
Vol 143 (3-4) ◽  
pp. 124-133 ◽  
Author(s):  
Mohammed Andaleeb Chowdhury ◽  
George V. Moukarbel ◽  
Rajesh Gupta ◽  
Stephanie Marie Frank ◽  
Ann M. Anderson ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Ventricular Dysfunction ◽  
Right Ventricular Dysfunction ◽  
Preserved Ejection Fraction ◽  
Heart Failure Hospitalization ◽  
Endothelin 1 ◽  
Long Term Mortality

Background: The prevalence of pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF) is increasing. We aim to study the role of big endothelin 1 (Big ET1), endothelin 1 (ET1), and neprilysin (NE) in HFpEF with PH. Method: This was a single center prospective cohort study including 90 HFpEF patients; 30 with no PH, 30 with postcapillary PH, and 30 with combined post- and precapillary PH. After enrollment, pulmonary venous and pulmonary arterial samples of Big ET1, ET1, and NE were collected during right heart catheterization. Subjects were then followed long term for adverse outcomes which included echocardiographic evidence of right ventricular dysfunction, heart failure hospitalization, and all-cause mortality. Results: Patients with HFpEF-PH were found to have increased ET1 in pulmonary veins (endothelin from the wedge; ET1W) compared to controls (2.3 ± 1.4 and 1.6 ± 0.9 pg/mL, respectively). ET1W levels were associated with both PH (OR 2.7, 95% CI 1.5–4.7, p = 0.01) and pulmonary vascular resistance (OR 1.6, 95% CI 1.04–2.3, p = 0.03). No evidence of right ventricular dysfunction was observed after 1 year of follow-up. ET1W (OR 1.8, 95% CI 1.2–2.6, p = 0.01) and ET1 gradient (ET1G; OR 1.4, 95% CI 1.04–2, p = 0.03) were predictive of 1-year hospitalization. ET1G ≥0.2 pg/mL was associated with long-term mortality (log-rank 4.8, p = 0.03). Conclusion: In HFpEF patients, ET1W and ET1G are predictive of 1-year heart failure hospitalization, while elevated ET1G levels were found to be associated with long-term mortality in HFpEF. This study highlights the role of ET1 in developing PH in HFpEF patients and also explores the potential of ET1 as a prognostic biomarker.

scholarly journals Natriuretic peptide receptor C contributes to disproportionate right ventricular hypertrophy in a rodent model of obesity-induced heart failure with preserved ejection fraction with pulmonary hypertension

2019 ◽  
Vol 9 (4) ◽  
pp. 204589401987859 ◽  
Author(s):  
Vineet Agrawal ◽  
Niki Fortune ◽  
Sheeline Yu ◽  
Julio Fuentes ◽  
Fubiao Shi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Ejection Fraction ◽  
Right Ventricular ◽  
Natriuretic Peptide ◽  
Ventricular Dysfunction ◽  
Control Diet ◽  
Right Ventricular Dysfunction ◽  
Cardiomyocyte Hypertrophy ◽  
Preserved Ejection Fraction

Heart failure with preserved ejection fraction (HFpEF) currently has no therapies that improve mortality. Right ventricular dysfunction and pulmonary hypertension are common in HFpEF, and thought to be driven by obesity and metabolic syndrome. Thus, we hypothesized that an animal model of obesity-induced HFpEF with pulmonary hypertension would provide insight into the pathogenesis of right ventricular failure in HFpEF. Two strains of mice, one susceptible (AKR) and one resistant (C3H) to obesity-induced HFpEF, were fed high fat (60% fat) or control diet for 0, 2, or 20 weeks and evaluated by cardiac catheterization and echocardiography for development of right ventricular dysfunction, pulmonary hypertension, and HFpEF. AKR, but not C3H, mice developed right ventricular dysfunction, pulmonary hypertension, and HFpEF. NPRC, which antagonizes beneficial natriuretic peptide signaling, was found in RNA sequencing to be the most differentially upregulated gene in the right ventricle, but not left ventricle or lung, of AKR mice that developed pulmonary hypertension and HFpEF. Overexpression of NPRC in H9C2 cells increased basal cell size and increased expression of hypertrophic genes, MYH7 and NPPA. In conclusion, we have shown that NPRC contributes to right ventricular modeling in obesity-induced pulmonary hypertension-HFpEF by increasing cardiomyocyte hypertrophy. NPRC may represent a promising therapeutic target for right ventricular dysfunction in pulmonary hypertension-HFpEF.

Right Heart Phenotype in Heart Failure With Preserved Ejection Fraction

2021 ◽  
Author(s):  
Marco Guazzi ◽  
Robert Naeije
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Right Ventricular ◽  
Ventricular Dysfunction ◽  
Imaging Techniques ◽  
Treatment Options ◽  
Right Ventricular Dysfunction ◽  
Preserved Ejection Fraction ◽  
Right Heart ◽  
The Right

The health burden of heart failure with preserved ejection fraction is increasingly recognized. Despite improvements in diagnostic algorithms and established knowledge on the clinical trajectory, effective treatment options for heart failure with preserved ejection fraction remain limited, mainly because of the high mechanistic heterogeneity. Diagnostic scores, big data, and phenomapping categorization are proposed as key steps needed for progress. In the meantime, advancements in imaging techniques combined to high-fidelity pressure signaling analysis have uncovered right ventricular dysfunction as a mediator of heart failure with preserved ejection fraction progression and as major independent determinant of poor outcome. This review summarizes the current understanding of the pathophysiology of right ventricular dysfunction in heart failure with preserved ejection fraction covering the different right heart phenotypes and offering perspectives on new treatments targeting the right ventricle in its function and geometry.

scholarly journals Pulmonary hypertension and right ventricular dysfunction in heart failure: prognosis and 15‐year prospective longitudinal trajectories in survivors

2020 ◽  
Vol 22 (7) ◽  
pp. 1214-1225 ◽  
Author(s):  
Evelyn Santiago‐Vacas ◽  
Josep Lupón ◽  
Giovana Gavidia‐Bovadilla ◽  
Francisco Gual‐Capllonch ◽  
Marta Antonio ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Ventricular Dysfunction ◽  
Right Ventricular Dysfunction ◽  
Longitudinal Trajectories ◽  
Failure Prognosis ◽  
Prospective Longitudinal
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