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Metabolic pathways associated with right ventricular adaptation to pulmonary hypertension: 3D analysis of cardiac magnetic resonance imaging.

ABSTRACT: AIMS:We sought to identify metabolic pathways associated with right ventricular (RV) adaptation to pulmonary hypertension (PH). We evaluated candidate metabolites, previously associated with survival in pulmonary arterial hypertension, and used automated image segmentation and parametric mapping to model their relationship to adverse patterns of remodelling and wall stress. METHODS AND RESULTS:In 312 PH subjects (47.1% female, mean age 60.8?±?15.9?years), of which 182 (50.5% female, mean age 58.6?±?16.8?years) had metabolomics, we modelled the relationship between the RV phenotype, haemodynamic state, and metabolite levels. Atlas-based segmentation and co-registration of cardiac magnetic resonance imaging was used to create a quantitative 3D model of RV geometry and function-including maps of regional wall stress. Increasing mean pulmonary artery pressure was associated with hypertrophy of the basal free wall (??=?0.29) and reduced relative wall thickness (? = -0.38), indicative of eccentric remodelling. Wall stress was an independent predictor of all-cause mortality (hazard ratio = 1.27, P?=?0.04). Six metabolites were significantly associated with elevated wall stress (??=?0.28-0.34) including increased levels of tRNA-specific modified nucleosides and fatty acid acylcarnitines, and decreased levels (? = -0.40) of sulfated androgen. CONCLUSION:Using computational image phenotyping, we identify metabolic profiles, reporting on energy metabolism and cellular stress-response, which are associated with adaptive RV mechanisms to PH.

SUBMITTER: Attard MI

PROVIDER: S-EPMC6529902 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Right ventricular (RV) function is a major determinant of outcome in patients with pulmonary hypertension. Cardiac magnetic resonance (CMR) is gold standard to assess RV ejection fraction (RVEFCMR), however this is a crude measure. New CMR measures of RV function beyond RVEFCMR have emerged, such as RV lateral atrio-ventricular plane displacement (AVPDlat), maximum emptying velocity (S'CMR), RV fractional area change (FACCMR) and feature tracking of the RV free wall (FWSCMR). However, it is not fully elucidated if these CMR measures are in parity with the equivalent echocardiography-derived measurements: tricuspid annular plane systolic excursion (TAPSE), S'-wave velocity (S'echo), RV fractional area change (FACecho) and RV free wall strain (FWSecho). The aim of this study was to compare regional RV function parameters derived from CMR to their echocardiographic equivalents in patients with pulmonary hypertension and to RVEFCMR. METHODS:Fifty-five patients (37 women, 62?±?15?years) evaluated for pulmonary hypertension underwent CMR and echocardiography. AVPDlat, S'CMR, FACCMR and FWSCMR from cine 4-chamber views were compared to corresponding echocardiographic measures and to RVEFCMR delineated in cine short-axis stack. RESULTS:A strong correlation was demonstrated for FAC whereas the remaining measurements showed moderate correlation. The absolute bias for S' was 2.4?±?3.0?cm/s (relative bias 24.1?±?28.3%), TAPSE/AVPDlat 5.5?±?4.6?mm (33.2?±?25.2%), FWS 4.4?±?5.8% (20.2?±?37.5%) and for FAC 5.1?±?8.4% (18.5?±?32.5%). In correlation to RVEFCMR, FACCMR and FWSecho correlated strongly, FACecho, AVPDlat, FWSCMR and TAPSE moderately, whereas S' had only a weak correlation. CONCLUSION:This study has demonstrated a moderate to strong correlation of regional CMR measurements to corresponding echocardiographic measures. However, biases and to some extent wide limits of agreement, exist between the modalities. Consequently, the equivalent measures are not interchangeable at least in patients with pulmonary hypertension. The echocardiographic parameter that showed best correlation with RVEFCMR was FWSecho. At present, FACecho and FWSecho as well as RVEFCMR are the preferred methods to assess and follow up RV function in patients with pulmonary hypertension. Future investigations of the CMR right ventricular measures, beyond RVEF, are warranted.

Project description:BackgroundPulmonary hypertension (PH) is known to alter the biventricular shape and temporal phases of the cardiac cycle. The presence of interventricular septal (IVS) displacement has been associated with the severity of PH. There has been limited cardiac magnetic resonance (CMR) data regarding the temporal parameters of the cardiac cycle in PH. This study aimed to quantify the temporal changes in the cardiac cycle derived from CMR in PH patients with and without IVS displacement and sought to understand the mechanism of cardiac dysfunction in the cardiac cycle.MethodsPatients with PH who had CMR and right heart catheterization (RHC) examinations were included retrospectively. Patients were divided into an IVS non-displacement (IVSND) group and an IVS displacement (IVSD) group according to IVS morphology, as observed on short-axis cine CMR images. Additionally, age-matched healthy volunteers were included as the health control (HC). Temporal parameters, IVS displacement, ventricular volume and functional parameters were obtained by CMR, and pulmonary hemodynamics were obtained by RHC. The risk stratification of the PH patients was also graded according to the guidelines.ResultsA total of 70 subjects were included, consisting of 33 IVSD patients, 15 IVSND patients, and 22 HC patients. In the IVSND group, only the right ventricle ejection fraction (RVEF) was decreased in the ventricular function, and no temporal change in the cardiac cycle was found. A prolonged isovolumetric relaxation time (IRT) and shortened filling time (FT) in both ventricles, along with biventricular dysfunction, were detected in the IVSD group (p < 0.001). The IRT of the right ventricle (IRTRV) and FT of the right ventricle (FTRV) in the PH patients were associated with pulmonary vascular resistance, right cardiac index, and IVS curvature, and the IRTRV was also associated with the RVEF in a multivariate regression analysis. A total of 90% of the PH patients in the IVSD group were stratified into intermediate- and high-risk categories, and they showed a prolonged IRTRV and a shortened FTRV. The IRTRV was also the predictor of the major cardiovascular events.ConclusionsThe temporal changes in the cardiac cycle were related to IVS displacement and mainly impacted the diastolic period of the two ventricles in the PH patients. The IRT and FT changes may provide useful pathophysiological information on the progression of PH.

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Metabolic pathways associated with right ventricular adaptation to pulmonary hypertension: 3D analysis of cardiac magnetic resonance imaging.

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