Hypercontractile phenotype at rest in chronic coronary syndromes predicts impaired functional reserve and increased mortality

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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.

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