A systematic assessment of causes of death after heart failure onset in the community: impact of age at death, time period, and left ventricular systolic dysfunction

Abstract

Background: The high mortality rate in patients with heart failure (HF) is influenced by presence of multiple comorbidities. Data are limited on the relative contributions of cardiovascular versus noncardiovascular diseases to death in individuals with HF in the community.

Methods and results: We examined the incidence and predictors of cardiovascular versus noncardiovascular death in participants with HF in the Framingham Heart Study. Underlying, immediate, and contributing causes of death (3 key elements of the World Health Organization classification) were adjudicated by a 3-physician review panel. During 1971 to 2004, 1025 participants with HF died (499 men, mean [SD] age at death 79 [11] years), including 463 participants with left ventricular ejection fraction (LVEF) data. Cardiovascular disease was the cause of death in 66.1% overall. Stratified by LVEF, cardiovascular deaths occurred in 44.5% and 69.9% of those with preserved and reduced LVEF, respectively. Presence of reduced LVEF increased the risk of cardiovascular death, with odds ratios of 3.16 (95% confidence interval [CI], 1.73 to 5.78) in men and 2.39 (95% CI, 1.39 to 4.08) in women. Prior myocardial infarction was associated with increased cardiovascular death in women with HF (odds ratio, 1.87; 95% CI, 1.10 to 3.16) but not in men. The risk of cardiovascular disease death decreased in women (odds ratio after 1980, 0.41; 95% CI, 0.24 to 0.69) and men (odds ratio, 0.66; 95% CI, 0.41 to 1.07, P=0.095) with HF over time. Infections and kidney disease emerged as key immediate and contributing causes of death, respectively.

Conclusions: Individuals with HF in the community often experience cardiovascular death, but noncardiovascular disease also contributes significantly especially among those with preserved LVEF.

Figure 1

Study cohorts available for death review. Primary death reviews for underlying cause of death were conducted in the largest HF cohort (n=1025). Detailed death reviews for underlying, immediate, and contributing causes of death were conducted in those with (n=463) and without (n=578) LV ejection fraction data available.

Figure 2. Cause of Death in Overall Cohort

Underlying and immediate causes of death by subcategories. Nearly two-thirds of underlying causes (total n=317 deaths) and nearly one-half of immediate causes (total n=313 deaths) were cardiovascular in nature.

Figure 3. Underlying Causes of Death in HFREF vs. HFPEF

Causes of death by sex and LV ejection fraction status. Deaths that were cardiovascular in nature occurred in approximately one-half of those with HFPEF (total n=109 deaths), and in nearly three-fourths of those with HFREF (total n=153 deaths), and were consistent between men and women.

Figure 4. Immediate Causes of Death in HFREF vs. HFPEF

Immediate causes of death by LV ejection fraction status. The majority of other cardiovascular deaths were contributed by arrhythmia, progressive pump failure (HFREF, n=152 deaths), and circulatory failure (HFPEF, n=106 deaths).