Low chronotropic response in post-myocardial infarction exercise test predicts worse prognosis in patients with preserved or mildly reduced left ventricular ejection fraction

Background: Chronotropic incompetence is prevalent in post-myocardial infarction (MI) patients and linked to reduced exercise capacity. However, its prognostic significance and the determination of threshold values for prognosis remain unclear. Methods: Ninety-six post-MI patients with left ventricular ejection fraction (LVEF) >= 40 % at four weeks post-event were assessed. All underwent combined exercise stress echocardiography and cardiopulmonary exercise testing (CPET-SE). The chronotropic response was expressed as a percentage of the maximal predicted heart rate (%MPHR) at peak exercise. The primary endpoint was a composite of all-cause mortality or unplanned hospitalization for coronary syndromes or heart failure. Results: Eighty-six patients completed follow-up (median: 4.0 years [IQR 2.0, 5.6]). The median age was 60 years (IQR 53, 65); 67 % were male, 86 % on beta-blockers. The median LVEF was 57 % (IQR 51, 62), and the median peak VO2 was 19 mL/kg/min (IQR 15, 22). Fifteen composite endpoint events, including three deaths, occurred. Multivariate Cox regression showed that %MPHR (HR 0.95, 95 % CI 0.92-0.98) and smoking history (HR 2.8, 95 % CI 1.1-7.4) were associated with the primary endpoint. A %MPHR threshold of 67 % best predicted the primary endpoint (AUC 73 %, PPV 29 %, NPV 95 %, sensitivity 87 %, specificity 55 %). Patients with %MPHR <67 % had significantly more composite endpoint events than those with %MPHR >= 67 % (p = 0.002). Conclusions: A chronotropic response below 67 % of the maximal predicted heart rate is a negative prognostic marker in post-MI patients with preserved or mildly reduced LVEF. This threshold may help risk-stratify and guide management in this population.