Quantification of Myocardial Deformation Applying CMR-Feature-Tracking—All About the Left Ventricle?

Purpose of Review Cardiac magnetic resonance-feature-tracking (CMR-FT)-based deformation analyses are key tools of cardiovascular imaging and applications in heart failure (HF) diagnostics are expanding. In this review, we outline the current range of application with diagnostic and prognostic implications and provide perspectives on future trends of this technique. Recent Findings By applying CMR-FT in different cardiovascular diseases, increasing evidence proves CMR-FT-derived parameters as powerful diagnostic and prognostic imaging biomarkers within the HF continuum partly outperforming traditional clinical values like left ventricular ejection fraction. Importantly, HF diagnostics and deformation analyses by CMR-FT are feasible far beyond sole left ventricular performance evaluation underlining the holistic nature and accuracy of this imaging approach. Summary As an established and continuously evolving technique with strong prognostic implications, CMR-FT deformation analyses enable comprehensive cardiac performance quantification of all cardiac chambers.

Contractile reprogramming of cardiac pericytes by MEK inhibition promotes arteriologenesis of the ischemic heart

BackgroundThe development of collateral arteries after a myocardial infarction (MI) was intensively studied, while the mechanism by which pericytes (PCs) contribute to arteriologenesis remains unexplored. This study aimed to 1) investigate if cardiac PCs gain functional features of contractile vascular smooth muscle cells (VSMCs) in vitro, and 2) determine if this potential can be evoked pharmacologically to encourage heart arteriologenesis in vivo.MethodsPCs were immunosorted as CD31neg/CD34pos cells from human and mouse hearts. Contractile reprogramming was induced by either depletion of growth factors or addition of PD0325901, a clinically available MEK inhibitor. Next generation RNA-Sequencing was performed in naïve and differentiated human PCs to assess the whole-transcriptome profile. Three in vivo studies were conducted in C57BL6/J mice to determine: 1) the ability of human PCs to promote arteriole formation when implanted subcutaneously within PD0325901-containing Matrigel plugs, 2) the effect of orally administered PD0325901 on the arteriole density of normoperfused hearts, and 3) the possibility of promoting capillary formation and muscularization of the infarcted heart through the same pharmacological approach.ResultsRemoval of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) from the culture medium induced the differentiation of PCs into contractile VSMC-like cells. Because both growth factors induce the extracellular signal-regulated kinase 1/2 (ERK1/2) signalling, we attempted to induce PC differentiation in vitro and in vivo using PD0325901. RNA-sequencing revealed that differentiated PCs were enriched in transcripts associated with smooth muscle contraction and biological function. PD0325901-treated PCs rapidly acquired antigenic and functional features of contractile VSMCs in vitro. Moreover, human PCs formed new arterioles when implanted subcutaneously within PD0325901-containing Matrigel plugs in mice. Oral administration of PD0325901 for two weeks increased the density and expression of contractile proteins in small-calibre arterioles of the murine heart, thereby increasing myocardial perfusion. Similarly, PD0325901 induced reparative arteriologenesis and capillarization, reduced the scar, and improved left ventricular performance in a murine model of MI.ConclusionWe propose a novel method to promote the heart vascularization through the pharmacological modulation of resident mural cells. This novel approach could have an immediate impact on the treatment of coronary artery disease.Clinical perspectiveWhat is new?Human myocardial pericytes have intrinsic vascular plasticity that can be pharmacologically evoked using PD0325901, a clinically available MEK inhibitor.In mice, the pharmacological inhibition of ERK1/2 signalling, by the oral administration of PD0325901 for 2 weeks, encouraged the heart arteriologenesis through pericyte differentiation.In a preclinical mouse model of myocardial infarction, the oral administration of PD0325901 for 2 weeks induced reparative arteriologenesis and capillarization, reduced the scar, and improved left ventricular performance.What are the clinical implications?This novel drug-based therapeutic approach is readily available to all patients.Therefore, it could have an immediate clinical impact for the treatment of coronary artery disease and other heart conditions associated with deficient coronary vascularization.

P657 Deterioration of left ventricular performance in response to pulmonary hypertension, in patients with scleroderma versus patients with coronary artery disease

Funding Acknowledgements PlaqueImage Background The relationship between the degree of pulmonary hypertension (PH) and left ventricular performance in patients with systemic sclerosis is still a controversial issue in the literature. We aimed to conduct a comparative analysis of indexes characterizing left ventricular systolic and diastolic function, in two etiological types of pulmonary hypertension involving different pathophysiological mechanisms: PH caused by systemic sclerosis and PH caused by myocardial ischemia. Material and method We performed a prospective study on 83 patients (36 patients with documented PAH with a systolic pulmonary arterial pressure – sPAP of >35 mmHg and 47 subjects with normal sPAP), out of which group 1 – with systemic sclerosis (n = 48); group 2 – significant coronary artery disease - CAD (n = 35). Patients of each group were divided in two subgroups based on the diagnosis of PH: group 1A - subjects with scleroderma and associated PH (n = 20), group 1B - subjects with scleroderma without PH (n = 28), group 2A - ischemic patients with associated PH (n = 16) and subgroup 2B - patients with ischemic disease without PH (n = 19). Results Patients in group 1 presented a significantly higher number of female subjects (p = 0.001) and a higher mean age (p = 0.009) compared to group 2. Patients with associated PH presented a significantly lower left ventricular ejection fraction (LVEF) compared to those without PH within the ischemic group (p = 0.023). There was a significant inverse correlation between the sPAP and LVEF in ischemic patients (r=-0.52, p = 0.001) as well as for scleroderma patients without PH (r=-0.51, p = 0.04). Tissue Doppler analysis of the left ventricular function indicated a significant negative correlation between the septal E’ value versus the sPAP and lateral E’ value versus the sPAP (r=-0.49, p = 0.002; r=-0.43, p = 0,008). Conclusions Intrinsic myocardial damage plays an important role in left ventricular systolic function even in the absence of PAH. Scleroderma patients present a less pronounced deterioration of the LVEF in response to pulmonary hypertension, indicating that in this group, additional compensatory mechanisms could be involved in the complex response of myocardium to elevated pulmonary pressures.