Echocardiographic Features of Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction

PARAGON-HF Investigators

doi:10.1016/j.jacc.2019.09.063

Echocardiographic Features of Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction

PARAGON-HF Investigators

Medicine, Cardiology Division

Research output: Contribution to journal › Article › peer-review

177 Scopus citations

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.

Original language	English (US)
Pages (from-to)	2858-2873
Number of pages	16
Journal	Journal of the American College of Cardiology
Volume	74
Issue number	23
DOIs	https://doi.org/10.1016/j.jacc.2019.09.063
State	Published - Dec 10 2019

Funding

The PARAGON-HF trial was funded by Novartis. The work for this paper was also supported by National Heart, Lung, and Blood Institute grants K08HL116792, R01HL135008, and R01HL143224 (Dr. Shah) and a Watkins Discovery Award from the Brigham and Women's Heart and Vascular Center (Dr. Shah). Dr. A.M. Shah has received research support from Novartis through Brigham and Women's Hospital; and has received consulting fees from Philips Ultrasound and Bellerophon Therapeutics. Dr. Cikes has received grants, personal fees, and nonfinancial support (travel support) from Novartis, GE Healthcare, Abbott, Roche Diagnostics, Bayer, Pfizer, Boehringer Ingelheim, Berlin-Chemie Menarini, Servier, Corvia, AstraZeneca, Sanofi Genzyme, Sandoz, Amgen, Orion Pharma, and Teva Pharmaceutical Industries. Dr. Rizkala and Mr. Lukashevich are employees of Novartis. Dr. Zile has received grants and personal fees from Novartis, CVRx, and Medtronic; and has received personal fees from Abbott, Boston Scientific, EBR, Endotronics, Ironwood, Merck, Myokardia, and V Wave. Dr. Lam has received research support from Boston Scientific, Bayer, Roche Diagnostics, AstraZeneca, Medtronic, and Vifor Pharma; has served as consultant or on Advisory Boards, Steering Committees, or Executive Committees for Boston Scientific, Bayer, Roche Diagnostics, AstraZeneca, Medtronic, Vifor Pharma, Novartis, Amgen, Merck, Janssen Research & Development, Menarini, Boehringer Ingelheim, Novo Nordisk, Abbott Diagnostics, Corvia, Stealth BioTherapeutics, JanaCare, Biofourmis, Darma, Applied Therapeutics, MyoKardia, WebMD Global, Radcliffe Group, and Corpus; and is a cofounder of eKo.ai. Dr. O'Meara or her institution has received research support from Novartis, AstraZeneca, Merck, Amgen, American Regent, and Bayer; and she has served as a consultant and/or speaker for Novartis, AstraZeneca, Amgen, Bayer, Pfizer, and Boehringer Ingelheim. Dr. S.J. Shah has received research grants from the National Institutes of Health (R01 HL107577, R01 HL127028, R01 HL140731, and R01 HL149423), Actelion, AstraZeneca, Corvia, and Novartis; and has served as a consultant or an Advisory Board member for Abbott, Actelion, AstraZeneca, Amgen, Bayer, Boehringer Ingelheim, Cardiora, Coridea, CVRx, Eisai, Ionis, Ironwood, Merck, MyoKardia, Novartis, Pfizer, Sanofi, Shifamed, Tenax, and United Therapeutics. Dr. McMurray's employer, Glasgow University, was paid by Novartis for his role as co–principal investigator of PARAGON-HF. Dr. Solomon has received research grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, BMS, Celladon, Cytokinetics, Eidos, Gilead, GSK, Ionis, Lone Star Heart, Mesoblast, MyoKardia, NIH/NHLBI, Novartis, Sanofi Pasteur, and Theracos; and has consulted for Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, BMS, Cardior, Corvia, Cytokinetics, Daiichi-Sankyo, Gilead, GSK, Ironwood, Merck, Myokardia, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AoBiome, Janssen, Cardiac Dimensions, and Tenaya. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Keywords

diastolic function
echocardiography
heart failure
preserved left ventricular function

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1016/j.jacc.2019.09.063

Cite this

@article{a94653f6fce7410ba6298f8b649359d7,

title = "Echocardiographic Features of Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction",

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.",

keywords = "diastolic function, echocardiography, heart failure, preserved left ventricular function",

author = "{PARAGON-HF Investigators} and Shah, {Amil M.} and Maja Cikes and Narayana Prasad and Guichu Li and Stoyan Getchevski and Brian Claggett and Adel Rizkala and Ilya Lukashevich and Eileen O'Meara and Ryan, {John J.} and Shah, {Sanjiv J.} and Wilfred Mullens and Zile, {Michael R.} and Lam, {Carolyn S.P.} and McMurray, {John J.V.} and Solomon, {Scott D.}",

note = "Publisher Copyright: {\textcopyright} 2019 American College of Cardiology Foundation",

year = "2019",

month = dec,

day = "10",

doi = "10.1016/j.jacc.2019.09.063",

language = "English (US)",

volume = "74",

pages = "2858--2873",

journal = "Journal of the American College of Cardiology",

issn = "0735-1097",

publisher = "Elsevier Inc.",

number = "23",

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TY - JOUR

T1 - Echocardiographic Features of Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction

AU - PARAGON-HF Investigators

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.

PY - 2019/12/10

Y1 - 2019/12/10

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.

AB - 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.

KW - diastolic function

KW - echocardiography

KW - heart failure

KW - preserved left ventricular function

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Echocardiographic Features of Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction

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