TY - JOUR
T1 - Characterization of the Obese Phenotype of Heart Failure With Preserved Ejection Fraction
T2 - A RELAX Trial Ancillary Study
AU - Reddy, Yogesh N.V.
AU - Lewis, Gregory D.
AU - Shah, Sanjiv J.
AU - Obokata, Masaru
AU - Abou-Ezzedine, Omar F.
AU - Fudim, Marat
AU - Sun, Jie Lena
AU - Chakraborty, Hrishikesh
AU - McNulty, Steven
AU - LeWinter, Martin M.
AU - Mann, Douglas L.
AU - Stevenson, Lynne W.
AU - Redfield, Margaret M.
AU - Borlaug, Barry A.
N1 - Funding Information:
Grant Support: The work was supported by grants RO1 HL128526 and U10 HL110262 (B.A.B.) and T32 HL007111 (Y.N.V.R.), by a research fellowship from the Uehara Memorial Foundation, Japan (M.O.), and by training grant U10HL110337 (Y.N.V.R., M.O., M.F., and L.W.S.) from the National Heart, Lung, and Blood Institute.Potential Competing Interests: Dr Shah has received grant from Actelion, AstraZeneca, Corvia, and Novartis; honorarium from Actelion, AstraZeneca, Corvia, and Novartis; consulting fees from Actelion, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cardiora, Eisai, Ionis, Ironwood, Merck, Novartis, Pfizer, Sanofi, and United Therapeutics; and fees for participation in review activities from CVRx. Dr Fudim serves as a consultant to Coridea, Axon Therapies, and Galvani and has received grant NIH T32 and American Heart Association Grant award. Dr LeWinter has received a National Heart, Lung, and Blood Institute Heart Failure Clinical Research Network grant and salary partially supported by this grant. Dr Mann has received grant U0-1 from the National Institutes of Health Heart Failure Network and consulting fees from the Bristol-Myers Squibb (data and safety monitoring board); serves as a consultant to LivaNova (steering committee), Novartis (steering committee), and Tenaya Therapeutics; is an employee at the Washington University School of Medicine; has a grant pending with the National Institutes of Health (R01); has received royalties for editing Braunwald's Heart Disease from Elseiver; and has stock options of Tenaya Therapeutics. The other authors report no competing interests. Grant Support: The work was supported by grants RO1 HL128526 and U10 HL110262 (B.A.B.) and T32 HL007111 (Y.N.V.R.), by a research fellowship from the Uehara Memorial Foundation, Japan (M.O.), and by training grant U10HL110337 (Y.N.V.R., M.O., M.F., and L.W.S.) from the National Heart, Lung, and Blood Institute. Potential Competing Interests: Dr Shah has received grant from Actelion, AstraZeneca, Corvia, and Novartis; honorarium from Actelion, AstraZeneca, Corvia, and Novartis; consulting fees from Actelion, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cardiora, Eisai, Ionis, Ironwood, Merck, Novartis, Pfizer, Sanofi, and United Therapeutics; and fees for participation in review activities from CVRx. Dr Fudim serves as a consultant to Coridea, Axon Therapies, and Galvani and has received grant NIH T32 and American Heart Association Grant award. Dr LeWinter has received a National Heart, Lung, and Blood Institute Heart Failure Clinical Research Network grant and salary partially supported by this grant. Dr Mann has received grant U0-1 from the National Institutes of Health Heart Failure Network and consulting fees from the Bristol-Myers Squibb (data and safety monitoring board); serves as a consultant to LivaNova (steering committee), Novartis (steering committee), and Tenaya Therapeutics; is an employee at the Washington University School of Medicine; has a grant pending with the National Institutes of Health (R01); has received royalties for editing Braunwald's Heart Disease from Elseiver; and has stock options of Tenaya Therapeutics. The other authors report no competing interests.
Funding Information:
Grant Support: The work was supported by grants RO1 HL128526 and U10 HL110262 (B.A.B.) and T32 HL007111 (Y.N.V.R.), by a research fellowship from the Uehara Memorial Foundation , Japan (M.O.), and by training grant U10HL110337 (Y.N.V.R., M.O., M.F., and L.W.S.) from the National Heart, Lung, and Blood Institute .
Funding Information:
Potential Competing Interests: Dr Shah has received grant from Actelion , AstraZeneca , Corvia , and Novartis ; honorarium from Actelion, AstraZeneca, Corvia, and Novartis; consulting fees from Actelion, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cardiora, Eisai, Ionis, Ironwood, Merck, Novartis, Pfizer, Sanofi, and United Therapeutics; and fees for participation in review activities from CVRx. Dr Fudim serves as a consultant to Coridea, Axon Therapies, and Galvani and has received grant NIH T32 and American Heart Association Grant award. Dr LeWinter has received a National Heart, Lung, and Blood Institute Heart Failure Clinical Research Network grant and salary partially supported by this grant. Dr Mann has received grant U0-1 from the National Institutes of Health Heart Failure Network and consulting fees from the Bristol-Myers Squibb (data and safety monitoring board); serves as a consultant to LivaNova (steering committee), Novartis (steering committee), and Tenaya Therapeutics; is an employee at the Washington University School of Medicine; has a grant pending with the National Institutes of Health (R01); has received royalties for editing Braunwald's Heart Disease from Elseiver; and has stock options of Tenaya Therapeutics. The other authors report no competing interests.
Publisher Copyright:
© 2019 Mayo Foundation for Medical Education and Research
PY - 2019/7
Y1 - 2019/7
N2 - Objective: To characterize the obese heart failure with preserved ejection fraction (HFpEF) phenotype in a multicenter cohort. Patients and Methods: This was a secondary analysis of the randomized clinical trial RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction) performed between October 1, 2008, and February 1, 2012. Patients with HFpEF were classified by body mass index (BMI) as obese (BMI≥35 kg/m2) and nonobese (BMI<30 kg/m2) for comparison. Results: Obese patients with HFpEF (n=81) were younger (median age, 64 [interquartile range (IQR), 67-79] years vs 73 [IQR, 56-70] years; P<.001) but had greater peripheral edema (31% [25] vs 9% [6]; P<.001), more orthopnea (76% [56] vs 53% [35]; P=.005), worse New York Heart Association class (P=.006), and more impaired quality of life (P<.001) as compared with nonobese patients with HFpEF (n=70). Despite more severe signs and symptoms, obese patients with HFpEF had lower N-terminal pro B-type natriuretic peptide level (median, 481 [IQR, 176-1183] pg/mL vs 825 [IQR, 380-1679] pg/mL [to convert to pmol/L, multiply by 0.118]; P=.007) and lower left atrial volume index (median, 38 [IQR, 31-47] mL/m2 vs 54 [IQR, 41-63] mL/m2; P<.001). Serum C-reactive protein (median, 5.0 [IQR, 2.4-9.9] mg/dL vs 2.7 [IQR, 1.6-5.4] mg/dL [to convert to mg/L, multiply by 10−3]; P<.001) and uric acid (median, 7.8 [IQR, 6.1-8.7] mg/dL vs 6.8 [IQR, 5.5-8.3] mg/dL; P=.03) levels were higher in obese HFpEF, indicating greater systemic inflammation, than in nonobese HFpEF. Peak oxygen consumption was impaired in obese HFpEF (median, 11.1 [IQR, 9.6-14.4] mL/kg per minute vs 13.1 [IQR, 11.3-14.7] mL/kg per minute; P=.008), as was submaximal exercise capacity (6-minute walk distance, 272 [IQR, 200-332] m vs 355 [IQR, 290-415] m; P<.0001). Conclusion: Obese HFpEF is associated with decreased quality of life, worse symptoms of heart failure, greater systemic inflammation, worse exercise capacity, and higher metabolic cost of exertion as compared with nonobese HFpEF. Further study is required to understand the pathophysiology and potential distinct treatments for patients with the obese phenotype of HFpEF. Trial Registration: clinicaltrials.gov
AB - Objective: To characterize the obese heart failure with preserved ejection fraction (HFpEF) phenotype in a multicenter cohort. Patients and Methods: This was a secondary analysis of the randomized clinical trial RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction) performed between October 1, 2008, and February 1, 2012. Patients with HFpEF were classified by body mass index (BMI) as obese (BMI≥35 kg/m2) and nonobese (BMI<30 kg/m2) for comparison. Results: Obese patients with HFpEF (n=81) were younger (median age, 64 [interquartile range (IQR), 67-79] years vs 73 [IQR, 56-70] years; P<.001) but had greater peripheral edema (31% [25] vs 9% [6]; P<.001), more orthopnea (76% [56] vs 53% [35]; P=.005), worse New York Heart Association class (P=.006), and more impaired quality of life (P<.001) as compared with nonobese patients with HFpEF (n=70). Despite more severe signs and symptoms, obese patients with HFpEF had lower N-terminal pro B-type natriuretic peptide level (median, 481 [IQR, 176-1183] pg/mL vs 825 [IQR, 380-1679] pg/mL [to convert to pmol/L, multiply by 0.118]; P=.007) and lower left atrial volume index (median, 38 [IQR, 31-47] mL/m2 vs 54 [IQR, 41-63] mL/m2; P<.001). Serum C-reactive protein (median, 5.0 [IQR, 2.4-9.9] mg/dL vs 2.7 [IQR, 1.6-5.4] mg/dL [to convert to mg/L, multiply by 10−3]; P<.001) and uric acid (median, 7.8 [IQR, 6.1-8.7] mg/dL vs 6.8 [IQR, 5.5-8.3] mg/dL; P=.03) levels were higher in obese HFpEF, indicating greater systemic inflammation, than in nonobese HFpEF. Peak oxygen consumption was impaired in obese HFpEF (median, 11.1 [IQR, 9.6-14.4] mL/kg per minute vs 13.1 [IQR, 11.3-14.7] mL/kg per minute; P=.008), as was submaximal exercise capacity (6-minute walk distance, 272 [IQR, 200-332] m vs 355 [IQR, 290-415] m; P<.0001). Conclusion: Obese HFpEF is associated with decreased quality of life, worse symptoms of heart failure, greater systemic inflammation, worse exercise capacity, and higher metabolic cost of exertion as compared with nonobese HFpEF. Further study is required to understand the pathophysiology and potential distinct treatments for patients with the obese phenotype of HFpEF. Trial Registration: clinicaltrials.gov
UR - http://www.scopus.com/inward/record.url?scp=85067567567&partnerID=8YFLogxK
U2 - 10.1016/j.mayocp.2018.11.037
DO - 10.1016/j.mayocp.2018.11.037
M3 - Article
C2 - 31272568
AN - SCOPUS:85067567567
SN - 0025-6196
VL - 94
SP - 1199
EP - 1209
JO - Mayo Clinic Proceedings
JF - Mayo Clinic Proceedings
IS - 7
ER -