Depressed Cardiac Mechanical Energetic Efficiency: A Contributor to Cardiovascular Risk in Common Metabolic Diseases—From Mechanisms to Clinical Applications

• Main Authors: Albert Juszczyk, Karolina Jankowska, Barbara Zawiślak, Andrzej Surdacki, Bernadeta Chyrchel
• Format: Article
• Language: English
• Published: MDPI AG 2020-08-01
• Series: Journal of Clinical Medicine
• Subjects: external cardiac work; cardiac mechanical energetic efficiency; noninvasive methods; cardiovascular risk; insulin resistance; diabetes
• Online Access: https://www.mdpi.com/2077-0383/9/9/2681

Cardiac mechanical energetic efficiency is the ratio of external work (EW) to the total energy consumption. EW performed by the left ventricle (LV) during a single beat is represented by LV stroke work and may be calculated from the pressure–volume loop area (PVLA), while energy consumption corresponds to myocardial oxygen consumption (MVO₂) expressed on a per-beat basis. Classical early human studies estimated total mechanical LV efficiency at 20–30%, whereas the remaining energy is dissipated as heat. Total mechanical efficiency is a joint effect of the efficiency of energy transfer at three sequential stages. The first step, from MVO₂ to adenosine triphosphate (ATP), reflects the yield of oxidative phosphorylation (i.e., phosphate-to-oxygen ratio). The second step, from ATP split to pressure–volume area, represents the proportion of the energy liberated during ATP hydrolysis which is converted to total mechanical energy. Total mechanical energy generated per beat—represented by pressure–volume area—consists of EW (corresponding to PVLA) and potential energy, which is needed to develop tension during isovolumic contraction. The efficiency of the third step of energy transfer, i.e., from pressure–volume area to EW, decreases with depressed LV contractility, increased afterload, more concentric LV geometry with diastolic dysfunction and lower LV preload reserve. As practical assessment of LV efficiency poses methodological problems, De Simone et al. proposed a simple surrogate measure of myocardial efficiency, i.e., mechano-energetic efficiency index (MEEi) calculated from LV stroke volume, heart rate and LV mass. In two independent cohorts, including a large group of hypertensive subjects and a population-based cohort (both free of prevalent cardiovascular disease and with preserved ejection fraction), low MEEi independently predicted composite adverse cardiovascular events and incident heart failure. It was hypothesized that the prognostic ability of low MEEi can result from its association with both metabolic and hemodynamic alterations, i.e., metabolic syndrome components, the degree of insulin resistance, concentric LV geometry, LV diastolic and discrete systolic dysfunction. On the one part, an increased reliance of cardiomyocytes on the oxidation of free fatty acids, typical for insulin-resistant states, is associated with both a lower yield of ATP per oxygen molecule and lesser availability of ATP for contraction, which might decrease energetic efficiency of the first and second step of energy transfer from MVO₂ to EW. On the other part, concentric LV remodeling and LV dysfunction despite preserved ejection fraction can impair the efficiency of the third energy transfer step. In conclusion, the association of low MEEi with adverse cardiovascular outcome might be related to a multi-step impairment of energy transfer from MVO₂ to EW in various clinical settings, including metabolic syndrome, diabetes, hypertension and heart failure. Irrespective of theoretical considerations, MEEi appears an attractive simple tool which couldt improve risk stratification in hypertensive and diabetic patients for primary prevention purposes. Further clinical studies are warranted to estimate the predictive ability of MEEi and its post-treatment changes, especially in patients on novel antidiabetic drugs and subjects with common metabolic diseases and concomitant chronic coronary syndromes, in whom the potential relevance of MEE can be potentiated by myocardial ischemia.