Patients with heart failure get pneumonia at a rate almost three times greater than expected and, once they do get pneumonia, have about a fourfold greater risk of death, investigators for a retrospective analysis of 13,000 patients from two landmark randomized HF trials have found.
The investigators also found that HF patients with preserved ejection fraction (HFpEF) are at the highest risk of developing pneumonia. The findings underscore the importance of patients with HF getting a pneumonia vaccination, they found.
The analysis showed that 6.3% of patients in the PARADIGM-HF trial and 10.6% of those in the PARAGON-HF trial developed pneumonia, reported the study authors, led by John J.V. McMurray, MD, of the British Heart Foundation Cardiovascular Research Center at the University of Glasgow in Scotland (J Am Coll Cardiol. 2021;77:1961-73).
“The main reason for doing this study was the fact that many heart failure patients are not vaccinated, as they should be, against pneumonia – both pneumococcus and influenza vaccination,” Dr. McMurray said in an interview. “We wanted to document the frequency and consequences of pneumonia in patients with heart failure to help highlight this deficiency in care.”
Dr. McMurray said he believes this is the first study to document the incidence of pneumonia and pneumonia-related outcomes according to the two major ejection fraction phenotypes.
PARADIGM-HF and PARAGON-HF
The post hoc analysis consisted of 8,399 patients with HF with reduced ejection fraction (HFrEF) in PARADIGM-HF (Eur J Heart Fail. 2013 Sep;15:1062-73) and 4,796 patients with HFpEF in PARAGON-HF (N Engl J Med. 2014 Sep 11;371:993-1004). The analysis focused on the 528 and 510 patients in each study, respectively, who developed pneumonia. Those rates translated to an incidence rate of 29 per 1,000 patient-years (95% confidence interval, 27-31) in PARADIGM-HF and 39 per 1,000 patient-years (95% CI, 36-42) in PARAGON-HF.
After pneumonia, the risk of death in patients increased substantially. In PARADIGM-HF, the adjusted hazard ratio for the risk of death from any cause after pneumonia was 4.34 (95% CI, 3.73-5.05). In PARAGON-HF, it was 3.76 (95% CI, 3.09-4.58). HF patients who contracted pneumonia also tended to have HF longer than their counterparts who didn’t develop pneumonia, but the frequency of previous hospitalization for HF didn’t vary between the pneumonia and no-pneumonia groups.
Patients who developed pneumonia tended to be older (average age of 66.9 years vs. 64.6 years, P < .001) and male (83.9% vs. 77.8%, P < .001). The mean age of patients in PARADIGM-HF was almost a decade younger than those in PARAGON-HF, 64 vs. 73 years.
Pneumonia patients also had worse Kansas City Cardiomyopathy Questionnaire scores (76 vs. 80 on average), but no difference in New York Heart Association functional class. “In general, patients who developed pneumonia had more symptoms and signs and HF than those who did not develop pneumonia,” Dr. McMurray and colleagues wrote.
Pneumonia patients also had higher rates of chronic obstructive pulmonary disease (26% vs. 12%), diabetes (43% vs. 34%), and atrial fibrillation (46% vs. 36%).
Another reason for conducting the study, Dr. McMurray said, “was the prior findings in patients with coronary disease and acute myocardial infarction that the risk associated with an episode of pneumonia [e.g., in subsequent vascular events and deaths] persisted long after the acute event. We wanted to see if this was also the case for heart failure, and indeed it was.”
For example, the adjusted HR for cardiovascular death or hospitalization in the first month following an episode of pneumonia was 9.48 (range of 6.85-13.12, P < .001), leveling off to 1.59 after 3 months or more.