In patients with heart failure with preserved ejection fraction (HFpEF), pulmonary disease may be an independent predictor of all-cause and heart failure hospitalizations but not mortality, according to a research letter published in the European Journal of Heart Failure.
Chronic obstructive pulmonary disease (COPD) is a prevalent condition that is predictive of poor outcomes in HFpEF, even in patients with preserved left ventricular ejection fraction (LVEF). In the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, investigators evaluated the influence of milder obstructive pulmonary disease (defined as the absence of steroid use or supplemental oxygen) on cardiovascular outcomes in patients with HFpEF (LVEF ≥45%). TOPCAT was a multicenter, double-blind, randomized, placebo-controlled trial designed to test the efficacy of spironolactone in reducing cardiovascular morbidity and mortality in 3445 participants ≥50 years old with HFpEF.
To avoid regional confounders, the current analysis was limited to the 1767 participants recruited in the Americas. Outcomes included the composite of cardiovascular death, aborted sudden death, or HF hospitalization (the TOPCAT primary outcome), the individual components of this composite, non-cardiovascular mortality, all-cause mortality, and all-cause hospitalization. Pulmonary disease at baseline was related to each outcome using multivariate Cox proportional hazards models adjusted for treatment group, age, gender, white race, enrollment strata, use of beta-blockers, percutaneous coronary intervention, body mass index, smoking status, and heart rate. Data were further adjusted for New York Heart Association (NYHA) class in separate models.
Obstructive pulmonary disease was independently associated with an increased risk of the primary composite outcome (adjusted hazard ratio [aHR], 1.31; 95% CI, 1.07-1.59; P =.001), HF hospitalization alone (aHR, 1.39; 95% CI 1.11-1.73; P =.003), and all cause hospitalization (aHR, 1.32; 95% CI, 1.15-1.52; P <.001). Of the 1765 American TOPCAT participants, 653 (37%) were included in the echocardiographic study, and 159 of the 653 (24%) had pulmonary disease (COPD or asthma).
Pulmonary disease was associated with smaller left atrial volume index and higher LVEF, without differences in pulmonary pressure or right ventricular function, suggesting that extracardiac factors could play an important role in mediating the increase in risk. When NYHA class was added to the model, only the association of pulmonary disease with HF hospitalization (hazard ratio [HR], 1.28; 95% CI, 1.03-1.60; P =.03) and all-cause hospitalization (HR ,1.28; 95% CI, 1.11-1.47; P <.01) persisted.
Study limitations included ascertaining pulmonary disease from medical history rather than pulmonary function testing and the potential misdiagnosis of COPD exacerbations as decompensated HF, which would result in an overestimation of cardiovascular events among patients with obstructive lung disease.
Disclosure: One study author declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Ramalho SHR, Claggett BL, Sweitzer NK, et al. Impact of pulmonary disease on the prognosis in heart failure with preserved ejection fraction: the TOPCAT trial [published online October 31, 2019]. Eur J Heart Fail. doi:10.1002/ejhf.1593