Pneumonia in HF Patients: High Risk, High Mortality

Patients with heart failure (HF)—especially those with preserved ejection fraction (HFpEF)—have a high incidence of pneumonia and are at an even greater risk of pneumonia than previously expected. In these patients, a first episode of pneumonia was associated with a 4-fold increased mortality risk, researchers found.

“Patients with HF are thought to be at 2-fold higher risk of pneumonia than age- and sex-matched individuals in the population, and survival from pneumonia is lower in patients with HF than in those without. Conversely, pneumonia increases the risk of worsening HF and is often considered a factor in decompensation leading to hospitalization,” John J.V. McMurray, MD, of the British Heart Foundation Cardiovascular Research Center, University of Glasgow, U.K., and fellow researchers wrote in the Journal of the American College of Cardiology.

Using data from two large trials—the PARADIGM-HF and PARAGON-HF trials—McMurray and colleagues conducted this retrospective analysis to assess the incidence of pneumonia and rates of HF hospitalization, cardiovascular mortality, and all-cause mortality before and after pneumonia, as well as how these risks differed between HF patients with reduced ejection fraction (HFrEF) and HFpEF.

The study authors pulled data from 8,399 patients with HFrEF from the PARADIGM-HF trial and 4,796 patients with HFpEF from the PARAGON-HF trial. The PARADIGM-HF trial only included patients with left ventricular ejection faction (LVEF) less than or equal to 40%, while patients with LVEF greater than or equal to 45% and LV hypertrophy, left atrial enlargement, or both were included in PARAGON-HF. Patients in both trials also had elevated B-type natriuretic peptide (BNP) or N-terminal pro-BNP levels.

Patients with HF had an unexpectedly high incidence of pneumonia, especially those with HFpEF, the study authors found. Among the HFrEF patients in the PARADIGM-HF trial, 6.3% developed pneumonia, for an incidence rate of 29 per 1,000 patient-years. In patients with HFpEF from the PARAGON-HF trial, 10.6% developed pneumonia, for an incidence rate of 39 per 1,000 patient-years.

After pneumonia, the adjusted hazard ratio (HR) for the risk of death from any cause was 4.34 (95% CI: 3.73-5.05) in the PARADIGM-HF trial and 3.7 (95% CI: 3.09-4.58) in the PARAGON-HF trial.

Patients who did develop pneumonia were older than those who did not (66.0 vs 63.6 years, respectively; P˂0.001), were more likely to be men (83.9% vs 77.8%; P˂0.001), were more likely to have HF of a longer duration, and had worse Kansas City Cardiomyopathy Questionnaire clinical summary scores (76 vs 80). No differences in NYHA scores were seen between the two groups.

Patients who developed pneumonia had more symptoms and signs of HF compared with those who did not, as well as more comorbidities, including chronic obstructive pulmonary disease (35.6% vs 12.0%, respectively), diabetes (42.6% vs 34.1%) and atrial fibrillation (45.6% vs 36.2%). Patients who developed pneumonia also had higher NT-proBNP levels and lower estimated glomerular filtration rates (eGFR) compared with patients who did not.

A first episode of pneumonia was associated with a 3- to 4-fold higher risk of cardiovascular and all-cause death. In addition, the risk of death was “front-loaded,” the study authors noted, being extremely high during the first month after an episode of pneumonia and remaining elevated by 2- to 4-fold during months one through three. After the first three months, the risk of mortality stabilized but was still 1.5- to 2-fold higher than before the episode of pneumonia.

McMurray and colleagues also found that treatment with sacubitril/valsartan had no effect on reducing the risk of pneumonia in either trial. In the PARADIGM-HF study, patients treated with sacubitril/valsartan had an HR of 0.99 (95% CI: 0.83-1.17; P=0.88) compared with those treated with enalapril. In the PARAGON-HF trial, the HR for this comparison was 0.97 (95% CI: 0.81-1.15; P=0.69).

“Although our findings show only an association between pneumonia and worse outcomes and do not prove cause and effect, there seems little doubt that prevention of pneumonia is important in patients with HF,” wrote McMurray and fellow researchers.

Their results and the knowledge they contribute about patients with HF are important not only in themselves, but when taken in the larger context of the current pandemic, noted Donna Mancini, MD, and Gregory T. Gibson, MD, of The Zena and Michael A. Weinger Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York City, in an accompanying editorial.

“In light of the Covid-19 pandemic, the risks and consequences of pneumonia have never been more apparent than during this past year. Although poor outcomes have been well-documented in patients with heart failure and Covid-19, other causes of pneumonia are a known source of increased morbidity and mortality in this population. Previous studies have shown that infection is a common cause of hospitalization in patients with heart failure, and pneumonia is associated with increased risk of mortality in patients who are hospitalized. Pneumonia can also contribute to the development of heart failure. As the prevalence of heart failure continues to rise, exploration of factors that contribute to poor outcomes is of utmost importance,” they wrote.

“As nations around the world race to control the spread of the latest novel respiratory pathogen, this study serves as an important reminder of the ever-present risk posed by pneumonia in patients with heart failure. Evidence continues to mount that the severity of heart failure symptoms and presence of common comorbidities also contribute to this increased risk, suggesting that aggressive optimization of guideline-directed medical therapy and management of comorbidities may be beneficial,” they added.

Limitations of the study include its retrospective and non-prespecified nature, inclusion of patients with less comorbidity than those in a real-world setting, cases of pneumonia were not adjudicated, and lack of information on specific causes of pneumonia.

1. According to a post-hoc analysis of the PARADIGM-HF and PARAGON-HF trials, the incidence of pneumonia is high in patients with heart failure (HF) at around three times the expected rate, especially in those with preserved ejection fraction (HFpEF).

2. In HF patients with both preserved and reduced ejection fraction, a first episode of pneumonia was associated with 4-fold higher mortality, and risks were greatest in the first three months after infection.

Liz Meszaros, Deputy Managing Editor, BreakingMED™

Cat ID: 3

Topic ID: 74,3,791,730,3,124,125,190,192,925