Utility of the Cardiovascular Physical Examination and Impact of Spironolactone in Heart Failure With Preserved Ejection Fraction

Abstract

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.

Keywords: diastolic heart failure; edema; physical examination; quality of life; spironolactone.

Figures

Figure 1:. Incidence Rates of Adverse Cardiovascular Events by Number of Signs of Congestion

Incidence rates expressed per 100 person-years shown by time-updated number of signs of congestion. Increasing number of signs of congestion was associated with increasing risk for each cardiovascular outcome. The corresponding incidence rates are shown in Supplementary Table 5. CV, cardiovascular; HF, heart failure.

Figure 2:. Average Number of Signs of Congestion During Follow-up by Randomization Arm

Spironolactone (red) reduced congestion more than placebo (blue) during the majority of follow-up, shown from baseline to the 54-month visit. Subsequent visits were truncated due to small number of individuals in both arms. Error bars denote 95% confidence intervals.