Chronotropic incompetence and negative chronotropic therapy in myocardial infarction patients during Phase 2 Cardiac Rehabilitation

Background Chronotropic incompetence (CI), a frequent sequela after myocardial infarction (MI), can negatively affect exercise capacity and quality of life (QoL). Targeted deprescription of negative chronotropic therapy (NCT) may be beneficial in selected patients with CI. Purpose We aimed to analyse the incidence and evolution of CI in relation to NCT during follow-up in our local post-MI Phase 2 Cardiac Rehabilitation Program (CRP). Methods Patients with ST-segment elevation MI (STEMI) or occlusion MI (OMI) between November 2021 and November 2024 who completed our Phase 2 CRP were included in a prospective registry. Exercise testing (ExECG) was performed before and after Phase 2. Peak VO2 (estimated or measured), predicted functional capacity (as % of FRIEND equation), and chronotropic reserve index (CRI) [(maximum heart rate – resting heart rate) / ([220-age] – resting heart rate)] were assessed. CI was defined as <80% CRI (≤62% in patients receiving NCT). NCT was recorded in absolute and equivalent doses standardized to bisoprolol 2.5mg units (B2.5EU). QoL was evaluated using the Short-Form 36-item (SF-36) questionnaire before and after Phase 2. Results Our cohort comprised 251 patients (mean age 61.84±10.7 years, 83.7% men, 50.2% previous smokers, and 22.7% with diabetes mellitus), most presenting with anterior and inferior STEMI (n=107, 42.6% for each). The mean LVEF was 52.25±10.2%, with 89 patients (35.5%) showing LVEF<50%. Most patients received NCT before Phase 2 CRP (n=216, 86.1%). On initial ExECG, 107 (42.6%) patients demonstrated CI. NCT use was associated with lower CRI (66.48±19.29 vs. 76.06±23.03%, p=0.02). Patients with CI had worse initial peak VO2 (21.77±8.34 vs. 29.13±8.57 mL/kg/min, p<0.001), lower predicted functional capacity (73.33±29.58 vs. 92.18±26.62%, p<0.001), and poorer baseline QoL scores. NCT deprescription was performed in 58 patients (23.1%), including 32 of 107 patients with CI (29.9%), which increased the proportion of patients not receiving NCT from 13.9% to 19.1% (p<0.05). This subgroup had lower initial CRI (60.26 vs. 70.09%, p=0.001), with no differences on final ExECG (CRI 67.02 vs. 68.82%, p=0.62). Among patients with initial CI who received NCT deprescription, we observed the largest improvement in CRI on final ExECG (+15.84%, ANOVA p<0.001). A similar absolute increase in peak VO2 was observed across initial CI and NCT deprescription categories (mean +3.62mL/kg/min, ANOVA p=0.83). A weak correlation was found between CRI and peak VO2 both before (R2 0.249) and after (R2 0.309) Phase 2 CRP. Conclusion A substantial proportion of patients exhibit CI after MI, which adversely affects functional capacity and QoL. Deprescription of NCT is associated with the most pronounced improvement in chronotropic response after Phase 2 CRP. The role of this strategy in post-MI patients with CI and no clear indication for NCT warrants further investigation.