Supra-normal values of resting left ventricular systolic function are associated with decreased survival: to good to be normal?

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Abstract Background Hyper-contractile phenotype of the left ventricle (LV) is generally considered prognostically benign, but recent data challenge this intuitive assumption. Aim To assess the effects of resting LV function on survival. Methods In a prospective, observational, multicenter study, we recruited 5,122 patients (age 65±11.1 years, 2974 males, 58%) with chronic coronary syndromes referred for resting transthoracic echocardiography with technically successful volumetric echocardiography in 14 accredited laboratories. All recruiting centers had a structured follow-up program with >90% follow-up rate. In each patient, we quantitatively assessed (by Simpson's biplane, apical single-plane or parasternal linear method) LV end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF). As a load-independent index of LV contractility, LV force was estimated as systolic blood pressure by cuff sphygmomanometer/ESV. All-cause death was the only considered outcome end-point. Results EF was 59±11% (normal reference sextile = 58.0–59.9%). Force was 4.51±2.11 mmHg/ml (normal reference sextile = 3.50–4.27 mmHg/ml). The correlation between EF and force was linear (r=0.585, p<0.001). After a median follow-up of 862 days, there were 265 all-cause deaths. Considering EF values, mortality was lowest in the highest sextile (>67%) and significantly higher in the lowest sextile (EF <52%): see figure, left panel. A U-shaped curve was found with force, with mortality values being lowest in the middle sextile and significantly higher in the lowest sextile (<2.59 mmHg/ml) and in the highest sextile (>6.36 mmHg/ml): see figure, right panel. At multivariable analysis, after adjustment for age, diabetes, EF, and prior myocardial infarction, both the highest sextile of force (HR 1.84, 95%, confidence intervals 1.12–3.03 p=0.015), and the lowest sextile of force (HR 1.77, 95%, confidence intervals 1.08–2.90 p=0.024) were associated with decreased survival. Conclusion Sub-normal values of resting ejection fraction and super- and sub-normal values of the force are associated with worse survival in patients with chronic coronary syndromes. This U-shaped curve of mortality is detectable only with the force, a load independent index of LV contractility: too much of a good thing such as LV contractility can be dangerous on the long-run. Funding Acknowledgement Type of funding sources: None.

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