Villari, B

Abstract Introduction Transthoracic echocardiography (TTE) identifies a hypercontractile phenotype (HP) in chronic coronary syndromes (CCS), characterized by elevated resting left ventricular (LV) elastance (force = systolic blood pressure/end-systolic volume). To evaluate the prognostic significance and functional correlates of HP. Methods In a prospective multicentre study, 10 677 patients with CCS underwent resting TTE to assess LV ejection fraction (EF), stroke volume, and force by quantitative volumetric echocardiography. All patients were followed for the endpoint of all-cause mortality. In a subset of 5834 patients, stress echocardiography (exercise or dobutamine) was performed for LV contractile reserve and heart rate reserve. Results Patients were stratified into Force quintiles (Q1–Q5). Patients with hypercontractile phenotype exhibited lower stroke volume at rest (Q5 = 34.8 ± 12.3 vs Q1–Q4 = 57.4 ± 19.1 mL; P < .01) and higher EF at rest (Q5 = 64.8 ± 6.9% vs Q1–Q4 = 58.1 ± 8.7%, P < .01). During a median follow-up of 24 months (interquartile range = 12–40 months), 509 deaths occurred. The exposure-adjusted death rate was lowest in Q3 (3.53–4.51 mmHg/mL; 1.03 per 100 person/years) and higher in Q1 (≤2.62 mmHg/mL, 2.88), Q2 (2.63–3.52 mmHg/mL, 1.86), Q4 (4.52–6.11 mmHg/mL, 1.56), and Q5 (HP, >6.11 mmHg/mL; 1.88; P < .0001 vs Q1 and Q3). Multivariable analysis identified HP (Q5; HR 1.531 vs Q3, 95% CI 1.116–2.099; P = .006) and EF (HR 0.963, 95% CI 0.953–0.972; P < .0001) as independent predictors of death. During exercise or dobutamine stress, HP showed reduced LV contractile reserve (ΔEF: Q5 = 4.3 ± 9.4% vs Q1–Q4 = 7.0 ± 9.3%; P < .001) and blunted heart rate reserve (Q5 = 1.77 ± 0.33 vs Q1–Q4 = 1.85 ± 0.39; P < .01). All patients with force-based LV contractile reserve >4.1 (present in 185, 3.2% of the population) survived. Conclusion Patients with CCS with HP assessed by resting TTE demonstrate higher mortality and multilayered functional impairment, including reduced LV contractile and chronotropic reserves. Hypercontractile phenotype improved the prediction of mortality by EF. A ‘stronger’ heart is, in fact, functionally and prognostically weaker.

Abstract Background Chronotropic incompetence (CI) is a biomarker of cardiac autonomic dysfunction. Aim To assess the risk stratification value of CI during physical or pharmacological stress echocardiography in patients with chronic coronary syndromes. Methods In a prospective, multicenter, international, observational study design, we enrolled 13,445 patients with known or suspected chronic coronary syndromes who underwent stress echo in 19 sites from 10 countries using either exercise (n=2,594), dobutamine (n=2,440), or dipyridamole (n=8,411). Heart rate was automatically measured from the 1-lead ECG in the echo monitor. We considered CI as failure to reach 85% of the maximal predicted (220-age) heart rate for exercise and dobutamine, and heart rate reserve (peak/rest heart rate) <1.22 (<1.17 in permanent atrial fibrillation) for dipyridamole. All-cause death was the outcome measure. Results Heart rate reserve was available in all patients; there was no extra imaging or analysis time, and no intra- and inter-observer variability. CI was observed in 5,045 patients (38%); abnormal regional wall motion abnormality in 1,648 (13%). Over a median follow-up time of 3.5 years, there were 2,426 (18%) deaths. The 10-year mortality was 39% in patients with and 21% in patients without CI (p<0.0001). CI was associated with a significant (p<0.0001) increase in 10-year mortality in all age groups ranging from <54 years to >75 years. In addition, it was associated with increased mortality (p<0.0001) irrespective of β-blocker use (Figure). Cox multivariable analysis revealed that CI was a significant predictor of mortality (HR 1.60, 95% confidence interval 1.47-1.74; p<0.0001) together with age, male sex, diabetes mellitus, ejection fraction, and resting heart rate. Conclusion In patients with chronic coronary syndromes, CI during physical or pharmacological stress is a simple, inexpensive, quantitative, and objective predictor of survival.