Abstract
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 Identifier: NCT00763867
Abbreviations and Acronyms:
6MWD (6-minute walk distance), BMI (body mass index), CPET (cardiopulmonary exercise testing), HF (heart failure), HFN (Heart Failure Clinical Research Network), HFpEF (heart failure with preserved ejection fraction), LV (left ventricular), MRI (magnetic resonance imaging), NT-proBNP (N-terminal pro B-type natriuretic peptide), NYHA (New York Heart Association), QOL (quality of life), RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction), Vo2 (oxygen consumption)To read this article in full you will need to make a payment
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Article Info
Footnotes
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.
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