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Echocardiographic Features of Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction.
J Am Coll Cardiol. 2019 12 10; 74(23):2858-2873.JACC

Abstract

BACKGROUND

The PARAGON-HF (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction) trial tested the efficacy of sacubitril-valsartan in patients with heart failure with preserved ejection fraction (HFpEF). Existing data on cardiac structure and function in patients with HFpEF suggest significant heterogeneity.

OBJECTIVES

The aim of this study was to characterize cardiac structure and function, quantify their associations with clinical outcomes, and contextualize these findings with other HFpEF studies.

METHODS

Echocardiography was performed in 1,097 of 4,822 PARAGON-HF patients within 6 months of enrollment. Associations with incident first heart failure hospitalization or cardiovascular death were assessed using Cox proportional hazards models adjusted for age, sex, region of enrollment, randomized treatment, N-terminal pro-brain natriuretic peptide, and clinical risk factors.

RESULTS

Average age was 74 ± 8 years, 53% of patients were women, median N-terminal pro-brain natriuretic peptide level was 918 pg/ml (interquartile range: 485 to 1,578 pg/ml), 94% had hypertension, and 35% had atrial fibrillation. The mean left ventricular (LV) ejection fraction was 58.6 ± 9.8%, prevalence of LV hypertrophy was 21%, prevalence of left atrial enlargement was 83%, prevalence of elevated E/e' ratio was 53%, and prevalence of pulmonary hypertension was 31%. Heart failure hospitalization or cardiovascular death occurred in 288 patients at 2.8-year median follow-up. In fully adjusted models, higher LV mass index (hazard ratio [HR]: 1.05 per 10 g/m2; 95% confidence interval [CI]: 1.00 to 1.10; p = 0.03), E/e' ratio (HR: 1.04 per unit; 95% CI: 1.02 to 1.06; p < 0.001), pulmonary artery systolic pressure (HR: 1.51 per 10 mm Hg; 95% CI: 1.29 to 1.76; p < 0.001), and right ventricular end-diastolic area (HR: 1.04 per cm2; 95% CI: 1.01 to 1.07; p = 0.003) were each associated with this composite, while LV ejection fraction and left atrial size were not (p > 0.05 for all). Appreciable differences were observed in cardiac structure compared with other HFpEF clinical trials, despite similar E/e' ratio, pulmonary artery systolic pressure, and event rates.

CONCLUSIONS

Diastolic dysfunction, left atrial enlargement, and pulmonary hypertension were common in PARAGON-HF. LV hypertrophy, elevated left- and right-sided pressures, and right ventricular enlargement were independently predictive of incident heart failure hospitalization or cardiovascular death. Echocardiographic differences among HFpEF trials despite similar clinical event rates highlight the heterogeneity of this syndrome. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).

Authors+Show Affiliations

Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address: ashah11@rics.bwh.harvard.edu.University of Zagreb School of Medicine and University Hospital Centre Zagreb, Department for Cardiovascular Diseases, Zagreb, Croatia.Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts.Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts.Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts.Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts.Novartis, East Hanover, New Jersey.Novartis, East Hanover, New Jersey.Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada.University of Utah, Salt Lake City, Utah.Northwestern University, Chicago, Illinois.Ziekenhuis Oost Limburg, Genk, Belgium.The Medical University of South Carolina and the Ralph H. Johnson VA Medical Center, Charleston, South Carolina.National Heart Centre Singapore and Duke-National University of Singapore, Singapore; University Medical Centre Groningen, Groningen, the Netherlands; The George Institute for Global Health, Newtown, New South Wales, Australia.University of Glasgow, Glasgow, United Kingdom.Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts.No affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31806129

Citation

Shah, Amil M., et al. "Echocardiographic Features of Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction." Journal of the American College of Cardiology, vol. 74, no. 23, 2019, pp. 2858-2873.
Shah AM, Cikes M, Prasad N, et al. Echocardiographic Features of Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction. J Am Coll Cardiol. 2019;74(23):2858-2873.
Shah, A. M., Cikes, M., Prasad, N., Li, G., Getchevski, S., Claggett, B., Rizkala, A., Lukashevich, I., O'Meara, E., Ryan, J. J., Shah, S. J., Mullens, W., Zile, M. R., Lam, C. S. P., McMurray, J. J. V., & Solomon, S. D. (2019). Echocardiographic Features of Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction. Journal of the American College of Cardiology, 74(23), 2858-2873. https://doi.org/10.1016/j.jacc.2019.09.063
Shah AM, et al. Echocardiographic Features of Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction. J Am Coll Cardiol. 2019 12 10;74(23):2858-2873. PubMed PMID: 31806129.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Echocardiographic Features of Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction. AU - Shah,Amil M, AU - Cikes,Maja, AU - Prasad,Narayana, AU - Li,Guichu, AU - Getchevski,Stoyan, AU - Claggett,Brian, AU - Rizkala,Adel, AU - Lukashevich,Ilya, AU - O'Meara,Eileen, AU - Ryan,John J, AU - Shah,Sanjiv J, AU - Mullens,Wilfred, AU - Zile,Michael R, AU - Lam,Carolyn S P, AU - McMurray,John J V, AU - Solomon,Scott D, AU - ,, PY - 2019/09/05/received PY - 2019/09/11/revised PY - 2019/09/16/accepted PY - 2019/12/7/entrez PY - 2019/12/7/pubmed PY - 2020/5/22/medline KW - diastolic function KW - echocardiography KW - heart failure KW - preserved left ventricular function SP - 2858 EP - 2873 JF - Journal of the American College of Cardiology JO - J. Am. Coll. Cardiol. VL - 74 IS - 23 N2 - BACKGROUND: The PARAGON-HF (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction) trial tested the efficacy of sacubitril-valsartan in patients with heart failure with preserved ejection fraction (HFpEF). Existing data on cardiac structure and function in patients with HFpEF suggest significant heterogeneity. OBJECTIVES: The aim of this study was to characterize cardiac structure and function, quantify their associations with clinical outcomes, and contextualize these findings with other HFpEF studies. METHODS: Echocardiography was performed in 1,097 of 4,822 PARAGON-HF patients within 6 months of enrollment. Associations with incident first heart failure hospitalization or cardiovascular death were assessed using Cox proportional hazards models adjusted for age, sex, region of enrollment, randomized treatment, N-terminal pro-brain natriuretic peptide, and clinical risk factors. RESULTS: Average age was 74 ± 8 years, 53% of patients were women, median N-terminal pro-brain natriuretic peptide level was 918 pg/ml (interquartile range: 485 to 1,578 pg/ml), 94% had hypertension, and 35% had atrial fibrillation. The mean left ventricular (LV) ejection fraction was 58.6 ± 9.8%, prevalence of LV hypertrophy was 21%, prevalence of left atrial enlargement was 83%, prevalence of elevated E/e' ratio was 53%, and prevalence of pulmonary hypertension was 31%. Heart failure hospitalization or cardiovascular death occurred in 288 patients at 2.8-year median follow-up. In fully adjusted models, higher LV mass index (hazard ratio [HR]: 1.05 per 10 g/m2; 95% confidence interval [CI]: 1.00 to 1.10; p = 0.03), E/e' ratio (HR: 1.04 per unit; 95% CI: 1.02 to 1.06; p < 0.001), pulmonary artery systolic pressure (HR: 1.51 per 10 mm Hg; 95% CI: 1.29 to 1.76; p < 0.001), and right ventricular end-diastolic area (HR: 1.04 per cm2; 95% CI: 1.01 to 1.07; p = 0.003) were each associated with this composite, while LV ejection fraction and left atrial size were not (p > 0.05 for all). Appreciable differences were observed in cardiac structure compared with other HFpEF clinical trials, despite similar E/e' ratio, pulmonary artery systolic pressure, and event rates. CONCLUSIONS: Diastolic dysfunction, left atrial enlargement, and pulmonary hypertension were common in PARAGON-HF. LV hypertrophy, elevated left- and right-sided pressures, and right ventricular enlargement were independently predictive of incident heart failure hospitalization or cardiovascular death. Echocardiographic differences among HFpEF trials despite similar clinical event rates highlight the heterogeneity of this syndrome. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711). SN - 1558-3597 UR - https://www.unboundmedicine.com/medline/citation/31806129/Echocardiographic_Features_of_Patients_With_Heart_Failure_and_Preserved_Left_Ventricular_Ejection_Fraction_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0735-1097(19)37991-4 DB - PRIME DP - Unbound Medicine ER -