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:
The data have been made available to other researchers for purposes of reproducing the results located on the National Institutes of Health website ( https://biolincc.nhlbi.nih.gov/studies/topcat/ ). The design of the TOPCAT trial has been described in detail previously. Briefly, TOPCAT was a multicenter, international, randomized, double blind, placebo-controlled trial of spironolactone in adults with HFpEF recruited from over 270 clinical sites. The trial was funded by the National Heart, Lung, and Blood Institute as a contract with the Brigham and Women’s Hospital (Clinical Coordinating Center) and the New England Research Institute (Data Coordinating Center). Enrollment began in August 2006 and ended in January 2012, and the primary results of the trial were published in April 2014 (mean follow-up was 3.5 years). The primary aim was to determine whether treatment with spironolactone, compared with placebo, can produce a clinically meaningful reduction in the composite outcome of cardiovascular mortality, aborted cardiac arrest, or HF hospitalization in adults with symptomatic HF and documented LVEF≥45%. All study participants provided written informed consent.
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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U2 - 10.1161/CIRCHEARTFAILURE.119.006125
DO - 10.1161/CIRCHEARTFAILURE.119.006125
M3 - Article
C2 - 31220936
AN - SCOPUS:85068494468
SN - 1941-3297
VL - 12
JO - Circulation: Heart Failure
JF - Circulation: Heart Failure
IS - 7
M1 - e006125
ER -
