Impact of Chronic Obstructive Pulmonary Disease in Patients With Heart Failure With Preserved Ejection Fraction: Insights From PARAGON-HF

Abstract

Background Little is known about the impact of chronic obstructive pulmonary disease (COPD) in patients with heart failure with preserved ejection fraction (HFpEF). Methods and Results We examined outcomes in patients with heart failure with preserved ejection fraction, according to COPD status, in the PARAGON-HF (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction) trial. The primary outcome was a composite of first and recurrent hospitalizations for heart failure and cardiovascular death. Of 4791 patients, 670 (14%) had COPD. Patients with COPD were more likely to be men (58% versus 47%; P<0.001) and had worse New York Heart Association functional class (class III/IV 24% versus 19%), worse Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores (69 versus 76; P<0.001) and more frequent history of heart failure hospitalization (54% versus 47%; P<0.001). The decrement in Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores with COPD was greater than for other common comorbidities. Patients with COPD had echocardiographic right ventricular enlargement, higher serum creatinine (100 μmol/L versus 96 μmol/L) and neutrophil-to-lymphocyte ratio (2.7 versus 2.5), than those without COPD. After multivariable adjustment, COPD was associated with worse outcomes: adjusted rate ratio for the primary outcome 1.51 (95% CI, 1.25-1.83), total heart failure hospitalization 1.54 (95% CI, 1.24-1.90), cardiovascular death (adjusted hazard ratio [HR], 1.42; 95% CI, 1.10-1.82), and all-cause death (adjusted HR, 1.52; 95% CI, 1.25-1.84). COPD was associated with worse outcomes than other comorbidities and Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores declined more in patients with COPD than in those without. Conclusions Approximately 1 in 7 patients with heart failure with preserved ejection fraction had concomitant COPD, which was associated with greater functional limitation and a higher risk of heart failure hospitalization and death. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711.

Keywords: chronic obstructive pulmonary disease; heart failure with preserved ejection fraction; right ventricle; sacubitril/valsartan.

Figure 1. Mean baseline Kansas City Cardiomyopathy Questionnaire scores associated with major comorbidities.

CKD indicates chronic kidney disease; and COPD, chronic obstructive pulmonary disease.

Figure 2. Clinical outcomes in heart failure with preserved ejection fraction according to COPD status at baseline.

A, Cumulative hazard estimate for the primary composite outcome. B, Cumulative hazard estimate for total hospitalizations for heart failure. C, Cumulative probability of cardiovascular death. D, Cumulative probability of all‐cause death. COPD indicates chronic obstructive pulmonary disease; and HF, heart failure.

Figure 3. Risk of primary outcome and all‐cause mortality associated with major comorbidities.

CKD indicates chronic kidney disease; and COPD; chronic obstructive pulmonary disease. Adjusted for treatment, sex, race, and N‐terminal pro‐B‐type natriuretic peptide (log) and stratified by region.