Distinct comorbidity clusters in acute HF affect clinical outcomes

17 Jun 2025
Distinct comorbidity clusters in acute HF affect clinical outcomes

A study involving 6,545 patients with acute heart failure (HF) has revealed five distinct groups of naturally clustered comorbid­ities, with the poorest postdischarge outcomes observed in the group with diabetes and chronic kidney disease (CKD), followed by the metabolic group and the elderly/atrial fibrillation (AF) group.

Latent class analysis was performed in patients hospitalized for symptomatic acute HF (mean age, 73 years; male, 60 percent; HF with preserved ejection fraction [HFpEF], 26 percent) enrolled in the prospective RELAX-AFH-2 trial to identify clusters of comor­bidities. [JACC Heart Fail 2024;12:1762-1774]

Five distinct multimorbidity groups were identified:

  1. Diabetes and CKD group (n=1,189; 18.16 percent) – highest number of comorbidities (n=8), high prevalence of diabetes (93.9 percent) and CKD (93.9 percent), and a 49.2 percent prevalence of obesity;
  2. Metabolic group (n=1,525; 23.3 percent) – highest prevalence of obesity (97.1 percent), hypertension (98.8 percent) and HFpEF (32.91 percent), and a high prevalence of diabetes (63.9 percent);
  3. Elderly/AF group (n=1,635; 24.98 percent) – oldest (mean age, 78.01 years), more likely female, lowest BMI (25.56 mg/ m2) and highest prevalence of AF (78.7 percent);
  4. Ischaemic group (n=973; 14.86 percent) – more likely male, more likely with HF with reduced ejection fraction (HFrEF), high prevalence of coronary artery disease (99.9 percent) and hyperlipidaemia (85.9 percent), lowest prevalence of CKD (43.6 percent), and highest prevalence of ischaemic HF aetiology (85.4 percent);
  5. Young group (n=1,223; 18.68 percent) – youngest (mean age, 69.43 years), fewer comorbidities (n=3), more likely with HFrEF, and highest prevalence of nonischaemic HF ae­tiology (72.5 percent).

After adjusting for confounders, patients in the diabetes and CKD group were found to have the highest risk of all-cause death or adjudicated hospitalization for HF or renal failure through 180 days compared with the young group (hazard ratio [HR], 1.80; 95 percent confidence interval [CI], 1.46–2.20; p<0.001). The risk of this composite adverse outcome was also increased in the elderly/AF group (HR, 1.42; 95 percent CI, 1.16–1.73; p<0.001) and the metabolic group (HR, 1.43; 95 percent CI, 1.17–1.75; p<0.001).

A significant interaction was seen between multimorbidity groups and treatment allocation on the risk of the composite out­come, which remained significant after adjustment for the number of comorbidities (pinteraction<0.001).

“These data highlight that the specific combination of multiple comorbidities can influence adverse outcomes and treatment re­sponses in patients with acute AF,” the researchers concluded.