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 (QoL), and influence of therapy in heart failure with preserved ejection fraction (HFpEF) 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 TOPCAT (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 HF hospitalization), its individual components, and all-cause mortality was assessed using timeupdated, multivariable-adjusted Cox regression analyses. We evaluated whether spironolactone improved congestion at 4-months, and whether improvement in congestion was related to QoL as assessed by Kansas City Cardiomyopathy Questionnaire clinical summary scores (KCCQ-OSS), 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 30-60% 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 to placebo. Each reduction in sign of congestion was independently associated with a 4.0 (95%CI: 2.4, 5.6) point improvement in KCCQ-OSS. When assessed simultaneously, timeupdated, but not baseline, congestion predicted outcomes. Conclusions: In HFpEF, the physical exam provides independent prognostic value for adverse outcomes. Spironolactone improved congestion compared with placebo. Reducing congestion was independently associated with improved QoL and outcomes and is a modifiable risk factor.

Application of Diagnostic Algorithms for Heart Failure With Preserved Ejection Fraction to the Community

“…Diagnosing is rendered more challenging by the presence of several comorbidities that may confound the diagnosis or be alternative causes of symptoms, as well as lack of proven biomarker thresholds or echocardiographic parameters. The diagnosis can be even more difficult among outpatients without frank pulmonary edema or jugular distention, but more subtle and less specific symptoms and signs such as dyspnea on exertion and edema (28). Accordingly, classifying HFpEF in such patients varies across studies.…”

Serum uric acid, influence of sacubitril–valsartan, and cardiovascular outcomes in heart failure with preserved ejection fraction: PARAGON‐HF

“…Finally, we assessed whether lowered SUA was associated with reductions in outcomes by simultaneously entering baseline and time-updated SUA into semiparametric or Cox models as appropriate with all outcomes, as employed previously. 23,24 Analyses were performed using STATA Version 14.0 (StataCorp LLC, College Station, TX, USA). A two-sided P-value of <0.05 was considered to indicate a difference of statistical significance.…”

Heart Failure with Reduced Ejection Fraction (HFrEF) and Preserved Ejection Fraction (HFpEF): The Diagnostic Value of Circulating MicroRNAs

“…Nevertheless, probable beneficial effects of these drugs in HFpEF patients were observed from different studies. For instance, in the TOPCAT trial, spironolactone (one of the MRAs) was reported to reduce congestion in HFpEF patients [38]. In the CHARM-preserved trial, candesartan (one of the ARBs) was shown to reduce HF admissions in HFpEF patients [39].…”