Myocardial work index: a marker of left ventricular contractility in pressure‐ or volume overload‐induced heart failure

AIMS: While global longitudinal strain (GLS) is considered to be a sensitive marker of left ventricular (LV) function, it is significantly influenced by loading conditions. We hypothesized that global myocardial work index (GMWI), a novel marker of LV function, may show better correlation with load‐independent markers of LV contractility in rat models of pressure‐induced or volume overload‐induced heart failure. METHODS AND RESULTS: Male Wistar rats underwent either transverse aortic constriction (TAC; n = 12) or aortocaval fistula creation (ACF; n = 12), inducing LV pressure or volume overload, respectively. Sham procedures were performed to establish control groups (n = 12/12). Echocardiographic loops were obtained to determine GLS and GMWI. Pressure‐volume analysis with transient occlusion of the inferior caval vein was carried out to calculate preload recruitable stroke work (PRSW), a load‐independent ‘gold‐standard’ parameter of LV contractility. Myocardial samples were collected to assess interstitial and perivascular fibrosis area and also myocardial atrial‐type natriuretic peptide (ANP) and brain‐type natriuretic peptide (BNP) relative mRNA expression. Compared with controls, GLS was substantially lower in the TAC group (−7.0 ± 2.8 vs. −14.5 ± 2.5%; P < 0.001) and was only mildly reduced in the ACF group (−13.2 ± 2.4 vs. −15.4 ± 2.0%, P < 0.05). In contrast with these findings, PRSW and GMWI were comparable with sham in TAC (110 ± 26 vs. 116 ± 68 mmHg; 1687 ± 275 mmHg% vs. 1537 ± 662 mmHg%; both P = NS), while it was found to be significantly reduced in ACF (58 ± 14 vs. 111 ± 40 mmHg; 1328 ± 411 vs. 1934 ± 308 mmHg%, both P < 0.01). In the pooled population, GMWI (r = 0.70; P < 0.001) but not GLS (r = −0.23; P = 0.12) showed a strong correlation with PRSW. GLS correlated with interstitial (r = 0.61; P < 0.001) and perivascular fibrosis area (r = 0.54; P < 0.001), and also with myocardial ANP (r = 0.85; P < 0.001) and BNP relative mRNA expression (r = 0.75; P < 0.001), while GMWI demonstrated no or only marginal correlation with these parameters. CONCLUSIONS: Being significantly influenced by loading conditions, GLS may not be a reliable marker of LV contractility in heart failure induced by pressure or volume overload. GMWI better reflects contractility in haemodynamic overload states, making it a more robust marker of systolic function, while GLS should be considered as an integrative marker, incorporating systolic function, haemodynamic loading state, and adverse tissue remodelling of the LV.