TY - JOUR
T1 - Utility of the Cardiovascular Physical Examination and Impact of Spironolactone in Heart Failure With Preserved Ejection Fraction
T2 - TOPCAT
AU - Selvaraj, Senthil
AU - Claggett, Brian
AU - Shah, Sanjiv J.
AU - Anand, Inder S.
AU - Rouleau, Jean L.
AU - Desai, Akshay S.
AU - Lewis, Eldrin F.
AU - Vaduganathan, Muthiah
AU - Wang, Stephen Y.
AU - Pitt, Bertram
AU - Sweitzer, Nancy K.
AU - Pfeffer, Marc A.
AU - Solomon, Scott D.
N1 - Funding Information:
This work was funded by the NHLBI, NIH, contract HHSN268200425207C. The content of this article does not necessarily represent the views of the NHLBI or of the Department of Health and Human Services.
Funding Information:
Dr Rouleau is a consultant for Novartis, Bayer, and AstraZeneca. Dr Pfeffer has received consulting fees from Aastrom, Abbott Vascular, Amgen, Cerenis, Concert, Daiichi Sankyo, Fibrogen, Genzyme, GlaxoSmithKline, Hamilton Health Sciences, Medtronic, Merck, Novo Nordisk, Roche, Salix, Sanderling, Sanofi Aventis, Serono, Servier, and Teva, as well as research grants from New England Research Institute via subcontract from the National Institutes of Health, Amgen, Celladon, Novartis, and Sanofi-Aventis. The Brigham and Women’s Hospital has patents for the use of inhibitors of the renin-angiotensin system in selected survivors of myocardial infarction with Novartis Pharmaceuticals on which Dr Pfeffer is a coinventor. His share of the licensing agreement is irrevocably transferred to charity. Dr Desai has received consulting fees from Novartis, AstraZeneca, Abbott, Relypsa, Boston Scientific, Corvidia, Boehringer Ingelheim, DalCor Pharma, and Signature Medical as well as research grants from Novartis. Dr Lewis has received research grants from the National Heart, Lung, and Blood Institute, Novartis, and Sanofi Aventis. Dr Vaduganathan is supported by the KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst (National Institutes of Health/NCATS Award UL 1TR002541) and serves on advisory boards for AstraZeneca, Bayer AG, and Baxter Healthcare. Dr Shah has received research grants from the American Heart Association, National Institutes of Health, Actelion, AstraZeneca, Corvia, and Novartis and consulting fees from Actelion, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Cardiora, Eisai, Gilead, Ironwood, Merck, MyoKardia, Novartis, Pfizer, Sanofi, and United Therapeutics. Dr Sweitzer has received research grants from the National Institutes of Health, Merck and Novartis. Dr Pitt reports receiving consulting fees from Amorcyte, AstraZeneca, Aurasense, Bayer, BG Medicine, Gambro, Johnson & Johnson, Mesoblast, Novartis, Pfizer, Relypsa, and Takeda; receiving research grant support from Forest Laboratories; and holding stock in Aurasense, Relypsa, BG Medicine, and Aurasense. Dr Pitt also reports a pending patent related to site-specific delivery of eplerenone to the myocardium. Dr Solomon has received consulting fees from Novartis and Bayer and research grants from the National Heart, Lung, and Blood Institute. The other authors report no conflicts.
Funding Information:
This work was funded by the NHLBI, NIH, contract HHSN268200425207C. The content of this article does not necessarily represent the views of the NHLBI or of the Department of Health and Human Services.
Publisher Copyright:
© 2019 American Heart Association, Inc.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - Background: The prognostic value of physical examination, its relation to quality of life, and influence of therapy in heart failure with preserved ejection fraction is not well known. Methods and Results: We studied participants from the Americas with available physical examination (jugular venous distention, rales, and edema) at baseline in the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist). The association of the number of signs of congestion with the primary outcome (cardiovascular death or heart failure hospitalization), its individual components, and all-cause mortality was assessed using time-updated, multivariable-adjusted Cox regression analyses. We evaluated whether spironolactone improved congestion at 4 months and whether improvement in congestion was related to quality of life as assessed by Kansas City Cardiomyopathy Questionnaire overall summary scores and to outcomes. Among 1644 participants, 22%, 54%, 20%, and 4% had 0, 1, 2, and 3 signs of congestion, respectively, at baseline. After multivariable adjustment, each additional increase in sign of congestion was associated with a 30% to 60% increased risk of each outcome (P<0.001). Spironolactone reduced the total number of signs of congestion by -0.10 (P=0.005) signs, jugular venous distention (odds ratio, 0.60; P=0.01), and edema (odds ratio, 0.74; P=0.006) at 4 months compared with placebo. Each reduction in sign of congestion was independently associated with a 4.0 (95% CI, 2.4-5.6) point improvement in Kansas City Cardiomyopathy Questionnaire overall summary score. When assessed simultaneously, time-updated, but not baseline congestion, predicted outcomes. Conclusions: In heart failure with preserved ejection fraction, the physical exam provides independent prognostic value for adverse outcomes. Spironolactone improved congestion compared with placebo. Reducing congestion was independently associated with improved quality of life and outcomes and is a modifiable risk factor. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00094302.
AB - Background: The prognostic value of physical examination, its relation to quality of life, and influence of therapy in heart failure with preserved ejection fraction is not well known. Methods and Results: We studied participants from the Americas with available physical examination (jugular venous distention, rales, and edema) at baseline in the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist). The association of the number of signs of congestion with the primary outcome (cardiovascular death or heart failure hospitalization), its individual components, and all-cause mortality was assessed using time-updated, multivariable-adjusted Cox regression analyses. We evaluated whether spironolactone improved congestion at 4 months and whether improvement in congestion was related to quality of life as assessed by Kansas City Cardiomyopathy Questionnaire overall summary scores and to outcomes. Among 1644 participants, 22%, 54%, 20%, and 4% had 0, 1, 2, and 3 signs of congestion, respectively, at baseline. After multivariable adjustment, each additional increase in sign of congestion was associated with a 30% to 60% increased risk of each outcome (P<0.001). Spironolactone reduced the total number of signs of congestion by -0.10 (P=0.005) signs, jugular venous distention (odds ratio, 0.60; P=0.01), and edema (odds ratio, 0.74; P=0.006) at 4 months compared with placebo. Each reduction in sign of congestion was independently associated with a 4.0 (95% CI, 2.4-5.6) point improvement in Kansas City Cardiomyopathy Questionnaire overall summary score. When assessed simultaneously, time-updated, but not baseline congestion, predicted outcomes. Conclusions: In heart failure with preserved ejection fraction, the physical exam provides independent prognostic value for adverse outcomes. Spironolactone improved congestion compared with placebo. Reducing congestion was independently associated with improved quality of life and outcomes and is a modifiable risk factor. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00094302.
KW - diastolic heart failure
KW - edema
KW - physical examination
KW - quality of life
KW - spironolactone
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UR - http://www.scopus.com/inward/citedby.url?scp=85068494468&partnerID=8YFLogxK
U2 - 10.1161/CIRCHEARTFAILURE.119.006125
DO - 10.1161/CIRCHEARTFAILURE.119.006125
M3 - Article
C2 - 31220936
AN - SCOPUS:85068494468
VL - 12
JO - Circulation: Heart Failure
JF - Circulation: Heart Failure
SN - 1941-3297
IS - 7
M1 - e006125
ER -
