Reflex and tonic autonomic markers for risk stratification in patients with type 2 diabetes surviving acute myocardial infarction

Abstract

Objective: Diabetic postinfarction patients are at increased mortality risk compared with nondiabetic postinfarction patients. In a substantial number of these patients, diabetic cardiac neuropathy already preexists at the time of the infarction. In the current study we investigated if markers of autonomic dysfunction can further discriminate diabetic postinfarction patients into low- and high-risk groups.

Research design and methods: We prospectively enrolled 481 patients with type 2 diabetes who survived acute myocardial infarction (MI), were aged ≤ 80 years, and presented in sinus rhythm. Primary end point was total mortality at 5 years of follow-up. Severe autonomic failure (SAF) was defined as coincidence of abnormal autonomic reflex function (assessed by means of heart rate turbulence) and of abnormal autonomic tonic activity (assessed by means of deceleration capacity of heart rate). Multivariable risk analyses considered SAF and standard risk predictors including history of previous MI, arrhythmia on Holter monitoring, insulin treatment, and impaired left ventricular ejection fraction (LVEF) ≤ 30%.

Results: During follow-up, 83 of the 481 patients (17.3%) died. Of these, 24 deaths were sudden cardiac deaths and 21 nonsudden cardiac deaths. SAF identified a high-risk group of 58 patients with a 5-year mortality rate of 64.0% at a sensitivity level of 38.0%. Multivariately, SAF was the strongest predictor of mortality (hazard ratio 4.9 [95% CI 2.4-9.9]), followed by age ≥65 years (3.4 [1.9-5.8]), and LVEF ≤ 30% (2.6 [1.5-4.4]).

Conclusions: Combined abnormalities of autonomic reflex function and autonomic tonic activity identifies diabetic postinfarction patients with very poor prognoses.

Figure 1

Cumulative rates of deaths, cardiac deaths, and sudden deaths in patients of the study population stratified according to the degree of autonomic dysfunction (NAF, MAF, SAF). The numbers of patients of the individual groups involved in the analysis at 0, 1, 2, 3, 4, and 5 years are shown below each graph; the order of the rows corresponds to the order of the mortality curves. *Test by log-rank statistics; **test according to Gray’s method.

Figure 2

Total mortality in patients with LVEF ≤30%, LVEF >30% and SAF, and LVEF >30% and MAF or NAF. The numbers of patients of the individual groups involved in the analysis at 0, 1, 2, 3, 4, and 5 years are shown below the graph; the order of the rows corresponds to the order of the mortality curves. Tests were done by log-rank statistics; pairwise comparisons: 1) LVEF >30% and MAF or NAF vs. LVEF >30% and SAF, P < 0.001; 2) LVEF >30% and MAF or NAF vs. LVEF ≤30%, P < 0.001; 3) LVEF >30% and SAF vs. LVEF ≤30%, P = 0.88.