Outcomes of Pneumonia in Patients With Heart Failure

Quick Takes

  • In post hoc analyses of two large, randomized cohorts with HFrEF and HFpEF patients, incidence of pneumonia was 29 and 39 per 1,000 patient-years, respectively.
  • Patients with pneumonia in both cohorts were older with more comorbid conditions.
  • Pneumonia was associated with an increased risk of two- to four-fold for HF hospitalization, all-cause mortality, and cardiovascular mortality in both HFrEF and HFpEF patients.

Study Questions:

What is the incidence and what are the associated outcomes with pneumonia in patients with heart failure (HF)?


This was a post hoc analysis of 8,399 patients with HF with reduced ejection fraction (HFrEF) randomized in the PARADIGM-HF trial, and 4,796 patients with HF with preserved EF (HFpEF) randomized in the PARAGON-HF trial. Both of these trials compared sacubitril/valsartan to a renin-angiotensin inhibitor alone in HF patients. PARADIGM-HF enrolled adults ≥18 years with EF ≤40%, and PARAGON-HF enrolled adults ≥50 years old with EF ≥45%. Primary endpoints for these trials were HF hospitalizations or cardiovascular death. In addition, the authors examined the association between pneumonia and all-cause mortality.


Among patients with HFrEF in the PARADIGM-HF trial, pneumonia developed in 6.3% of patients with an incidence of 29 per 1,000 patient-years. Patients who developed pneumonia were older, males, and had a longer duration of HF with a high comorbidity burden compared to those without pneumonia. Incidence of HF hospitalization (hazard ratio [HR], 2.39; 95% confidence interval [CI], 1.86-3.07), cardiovascular cause mortality (HR, 3.62; 95% CI, 3.02-4.34), and all-cause mortality (HR, 4.34; 95% CI, 3.73-5.05) were higher in patients with pneumonia despite multivariable adjustment.

In patients with HFpEF in the PARAGON-HF trial, 10.6% developed pneumonia with an incidence of 39 per 1,000 patient-years. In PARAGON-HF, patients who developed pneumonia compared to those who did not, were older with a higher frequency of HF hospitalizations and greater comorbidity burden as well. Pneumonia was significantly associated with HF hospitalization (HR, 1.98; 95% CI, 1.52-2.58), cardiovascular death (HR, 3.03; 95% CI, 2.31-3.98), and all-cause mortality (HR, 3.76; 95% CI, 3.09-4.58).

Association between pneumonia and adverse outcomes in both cohorts persisted after exclusion of hospitalizations where pneumonia and HF exacerbation co-existed. The risk was also front loaded with the highest risk in the first month with a steep decline thereafter. Sacubitril/valsartan use did not impact incidence of pneumonia in both cohorts.


In post hoc analyses of two large, randomized trials with HFrEF and HFpEF patients, incidence of pneumonia was high. Pneumonia was more prevalent in HFpEF patients than HFrEF patients. Pneumonia was associated with an over three-fold increase in risk for HF hospitalization, all-cause, and cardiovascular mortality in both cohorts.


Contemporary treatment of patients with HF places a heavy focus on guideline directed-medical therapy in HFrEF patients and specific therapies lack for HFpEF patients. In this study, pneumonia had a high incidence in HFrEF and HFpEF patients and was associated with over a three-fold risk for death and HF hospitalization in both cohorts. Despite effective vaccinations against Streptococcal pneumonia and influenza and despite guidelines recommending them, vaccination rates remain low. Findings of this study highlight that this may be a missed opportunity specifically in HFpEF patients where the incidence of pneumonia was noted to be higher.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure

Keywords: Angiotensins, Comorbidity, Heart Failure, Influenza, Human, Pneumonia, Renin-Angiotensin System, Risk, Stroke Volume, Secondary Prevention, Vaccination, Ventricular Dysfunction, Left

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