Baseline characteristics
In the study population, 2,321 patients with AHF had DM (43.0%) (Table 1). Patients with DM had a higher prevalence of risk factors like old age, obesity, hypertension, ischemic heart disease, chronic kidney disease, and cerebrovascular disease. Patients with DM had a higher proportion of patients with a BNP ≥500 pg/mL or NT-proBNP ≥1000 pg/mL, NYHA class III-IV on admission, acute pulmonary edema on chest X-ray, a higher level of systolic blood pressure, C-reactive protein, serum potassium and creatinine concentration, and lower serum sodium concentration and LVEF compared to those without DM. Besides, patients with DM were more likely to be on parenteral diuretics, inotropic agents, and vasodilators. However, aldosterone antagonists were prescribed less frequently in patients with DM.
All patients underwent echocardiography during their index admission (Table 1). There were no significant differences in the LV end-diastolic dimension (LVEDD) and LV end-systolic dimension (LVESD) between the two groups. However, there was a significant difference in the LVEF (38.5±15.9% vs. 36.7±15.0%, p<0.001). Furthermore, LV diastolic function parameters such as E/e’ (20.1±10.8 vs. 22.7±12.2, p<0.001) and right ventricular (RV) systolic pressure (43.2±14.9 mmHg vs. 44.9±15.4 mmHg, p<0.001) were worse in patients with DM. Conversely, patients without DM had a larger LA volume index (66.7±41.9 mL/m2 vs. 59.6±42.0 mL/m2, p<0.001).
In-hospital and overall mortality as per DM status
During a median follow-up of 3.5 years, there were 235 (4.4%) deaths during the index hospitalization, and 2,500 (46.3%) deaths during the overall follow-up period. Patients with DM had a higher incidence of in-hospital mortality and overall mortality compared to patients without DM (Figure 2). After adjusting for potential confounders including age, sex, BMI, etiology of heart failure (ischemic vs. non-ischemic), prior admission for HF, parenteral inotropic use, serum creatinine concentration, elevated BNP/NT-proBNP, NYHA class III-IV on admission, and smoking status, DM was still independently associated with overall mortality (adjusted hazard rate [HR] 1.11, 95% confidence interval [CI] 1.03–1.22).
Independent predictors of in-hospital and overall mortality
Results of multivariable Cox proportional hazard regression for in-hospital and overall all-cause mortality are reported in Table 2. DM was not independently associated with an increased in-hospital mortality (HR 0.81, 95% CI 0.61-1.07, p=0.137). Use of parenteral inotropes, age, ischemic etiology, and a higher serum creatinine concentration also independently predicted in-hospital mortality.
DM was an independent predictor for overall mortality (HR 1.11, 95% CI 1.03-1.22, p=0.013). Other variables, such as old age, male sex, higher BMI, ischemic etiology, acute decompensated HF, use of parenteral inotropes, high concentrations of serum creatinine and BNP/NT-proBNP during index hospitalization, and NYHA class III-IV on admission also independently predicted higher overall mortality.
In-hospital and overall mortality according to DM in subgroup by LVEF
Patients with DM had a higher in-hospital mortality rate vs. patients without DM in all LVEF subgroups (HFrEF 7.1% vs. 3.4%, HFmrEF 4.3% vs. 3.2%, HFpEF 3.8% vs. 2.7%). However, there was no significant association of DM with higher in-hospital mortality rate after adjusting for potential confounders (HFrEF, adjusted HR 0.96, 95% CI 0.68–1.35, HFmrEF, adjusted HR 0.71, 95% CI 0.33–1.53, HFpEF, adjusted HR 0.79, 95% CI 0.41–1.51) (Table 3).
DM had differential impact on overall mortality as per the HF subtype. In HFrEF, DM was significantly associated with an increased risk of overall mortality after adjusting for potential confounders (adjusted HR 1.14, 95% CI 1.02–1.27). However, DM was not significantly associated with overall mortality in patients with HFmrEF (adjusted HR 0.99, 95% CI 0.80–1.22) and HFpEF (adjusted HR 1.13, 95% CI 0.96–1.34) (Table 3). The Kaplan-Meier analysis also revealed significantly worse overall mortality in patients with HFrEF and DM vs. HFrEF and no DM (40.2% vs. 52.7%, log-rank p<0.001) (Figure 3).
Overall mortality as per the prespecified subgroup and glycemic control
Figure 4 shows the association between DM and overall mortality in a stratified group as per the potential confounders, including age, sex, ischemic etiology, hypertension, chronic kidney disease, de novo HF, LVEF <40%, and smoking status. The impact of DM on overall mortality was generally consistent across stratified subgroups (p-interaction ≥0.05). However, there was a significant difference in the impact of DM on overall mortality between smoker (current or ex-smoker) and never-smoker (p for interaction=0.022).
Figure 5 shows that patients with uncontrolled DM (HbA1c ≥7.0%) had significantly higher overall mortality compared to patients with well-controlled DM (HbA1c <7.0%) by Kaplan-Meier analysis (44.0% vs. 36.8%, log-rank p=0.016).