Prognostic correlates of hypercontractile phenotype and left ventricular contractile reserve based on the force

Background Left ventricular contractile reserve (LVCR) can be assessed using left ventricular end-systolic elastance (force), a relatively load-independent index of myocardial contractility. A hypercontractile phenotype (HP) is characterized by elevated resting LV force, defined as systolic blood pressure divided by end-systolic volume. Objectives To evaluate the prognostic significance of HP and LVCR in patients with chronic coronary syndromes (CCS). Methods In this prospective, multicenter study, 9,526 patients with CCS (41.2% women; age 65 ± 11 years; ejection fraction 61.6 ± 5.9%) underwent resting and stress echocardiography (SE) in 36 certified laboratories across 17 countries. Stress modality—exercise or pharmacologic (dobutamine or vasodilator)—was selected according to local practice, expertise, and patient characteristics. The primary endpoint was all-cause mortality. HP was defined as resting force >6.11 mmHg/ml. LVCR was calculated as the stress/rest force ratio and considered reduced if ≤1.1 for vasodilator SE and ≤1.6 for exercise or dobutamine SE, based on ROC curve analysis (sensitivity 57.8%, specificity 58.3%). Results HP was present in 2,058 patients (21.6%), and reduced LVCR was observed in 2,793 (29.3%). Compared with patients with normal resting force, those with HP showed higher force at rest (8.47 ± 2.24 vs 3.76 ± 1.17 mmHg/ml, p<0.001) and at peak stress (12.67 ± 5.19 vs 6.42 ± 3.19 mmHg/ml, p<0.001), but lower LVCR (1.51 ± 0.53 vs 1.74 ± 0.74, p<0.001). During a median follow-up of 24 months (interquartile range 13–39 months), 381 deaths (4.0%) occurred. Mortality was significantly higher in patients with concomitant HP and reduced LVCR (Figure 1). On multivariable analysis, the combination of HP and reduced LVCR (HR 2.37, 95% CI 1.74–3.23; p<0.001), age (HR 1.06 per year, 95% CI 1.05–1.07; p<0.001), and resting ejection fraction (HR 0.96 per %, 95% CI 0.95–0.984; p<0.0001) were independent predictors of death. Inducible regional wall motion abnormalities predicted mortality at univariable analysis (HR 1.47, 95% CI 1.10–1.97; p=0.009), but not after multivariable adjustment. Conclusions In patients with CCS, the combination of resting HP and reduced LVCR identifies a high-risk subgroup. The prognostic value of HP plus LVCR exceeds that of inducible regional wall motion abnormalities.