Prevalence and Predictors of Sepsis Death in Patients With Chronic Heart Failure and Reduced Left Ventricular Ejection Fraction

Abstract

Background Noncardiovascular death is increasingly common in people with chronic heart failure ( CHF ), yet its causes remain poorly characterized. We aimed to define the prevalence of sepsis death in people with CHF and to ascertain its risk marker profile. Methods and Results We conducted a prospective cohort study of 1802 patients with CHF and left ventricular ejection fraction ≤45% attending CHF clinics in 4 United Kingdom hospitals between 2006 and 2014. Mode of death was defined over a 10.3-year follow-up period (mean 4 years). Competing risk regression defined mode-specific hazard ratios for sepsis, other noncardiovascular, progressive heart failure, and sudden cardiac death in relation to established heart failure prognostic markers. Of 737 deaths, 173 (23.5%) were due to sepsis; respiratory tract infections accounted for 69.9% (n=121) of these events. Those who died from sepsis were older, had higher platelet counts, and had a higher prevalence of chronic obstructive pulmonary disease than those who died from other causes. Sepsis death was independently associated with older age (hazard ratio=1.05; 95% confidence interval 1.03-1.07), greater prevalence of chronic obstructive pulmonary disease (2.43; 1.74-3.40), male sex (1.73; 1.16-2.60), lower log serum vitamin D (0.68; 0.49-0.95), and higher platelet count (1.002; 1.000-1.005) than nonsepsis death. Established heart failure prognostic markers exhibited different patterns of association with sepsis death, other noncardiovascular death, progressive heart failure death, and sudden cardiac death. Conclusions Sepsis is a major contributor to death in people with CHF and has a different risk marker profile from other modes of death, suggesting that it may be amenable to targeted preventative strategies.

Keywords: heart failure; morbidity/mortality; sepsis.

Figure 1

Sepsis death in relation to other common modes of death. A, Relative contribution of modes of death to overall mortality, with sepsis (represented by the hatched region) accounting for over half of noncardiovascular deaths. B, Relative contribution of primary sources of sepsis to overall sepsis deaths. CV indicates cardiovascular; GI, gastrointestinal; HF, heart failure.

Figure 2

Cumulative incidence of sepsis death in relation to other common modes of death. Cumulative incidence functions illustrating sepsis, other noncardiovascular, progressive heart failure, and sudden cardiac death during follow‐up.

Figure 3

Predictors of sepsis death differ from those of alternate modes of death. Heat map of relative variable contributions to multivariate models predicting mode‐specific or all‐cause mortality, illustrating the distinct risk marker association with sepsis death. More intense red tones denote a greater percentage contribution of a variable to the global Wald score for prediction of a specific mode of death. COPD indicates chronic obstructive pulmonary disease; CV, cardiovascular; eGFR, estimated glomerular filtration rate; HF, heart failure; Ln, natural logarithm; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association.