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Right Ventricular Diastolic Performance in Patients With Chronic Thromboembolic Pulmonary Hypertension Assessed by Echocardiography.

ABSTRACT: Background: There have been no systemic studies about right heart filling pressure and right ventricular (RV) distensibility in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Therefore, we aimed to explore combinations of echocardiographic indices to assess the stages of RV diastolic dysfunction. Methods and Results: We recruited 32 healthy volunteers and 71 patients with CTEPH. All participants underwent echocardiography, cardiac catheterization (in patients with CTEPH), and a 6-min walk test (6MWT). The right atrial (RA) end-systolic area was adjusted for body surface area (BSA) (indexed RA area). RV global longitudinal diastolic strain rates (SRs) and RV ejection fraction (EF) were measured by speckle tracking and three-dimensional echocardiography (3D echo), respectively. All 71 patients with CTEPH underwent pulmonary endarterectomy. Of the 71 patients, 52 (73%) had decreased RV systolic function; 12 (16.9%), 26 (36.6%), and 33 (46.5%) patients had normal RV diastolic pattern, abnormal relaxation (stage 1), and pseudo-normal patterns (stage 2), respectively. The receiver operating characteristic curve analysis showed that the optimal cut-off values of early diastolic SR <0.8 s-1 and indexed RA area > 8.8 cm2/BSA had the best accuracy in identifying patients with RV diastolic dysfunction, with 87% sensitivity and 82% specificity. During a mean follow-up of 25.2 months after pulmonary endarterectomy, the preoperative indexed RA area was shown as an independent risk factor of the decreased 6MWT distance. Conclusions: Measuring early diastolic SR and indexed RA area would be useful in stratifying RV diastolic function.

SUBMITTER: Meng H

PROVIDER: S-EPMC8660143 | biostudies-literature |

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:Right ventricular (RV) diastolic function is impaired in patients with pulmonary arterial hypertension (PAH). Our previous study showed that elevated cardiomyocyte stiffness and myofilament Ca(2+) sensitivity underlie diastolic dysfunction in PAH. This study investigates protein modifications contributing to cellular diastolic dysfunction in PAH.RV samples from PAH patients undergoing heart-lung transplantation were compared to non-failing donors (Don). Titin stiffness contribution to RV diastolic dysfunction was determined by Western-blot analyses using antibodies to protein-kinase-A (PKA), C? (PKC?) and Ca(2+)/calmoduling-dependent-kinase (CamKII?) titin and phospholamban (PLN) phosphorylation sites: N2B (Ser469), PEVK (Ser170 and Ser26), and PLN (Thr17), respectively. PKA and PKC? sites were significantly less phosphorylated in PAH compared with donors (P<0.0001). To test the functional relevance of PKA-, PKC?-, and CamKII?-mediated titin phosphorylation, we measured the stiffness of single RV cardiomyocytes before and after kinase incubation. PKA significantly decreased PAH RV cardiomyocyte diastolic stiffness, PKC? further increased stiffness while CamKII? had no major effect. CamKII? activation was determined indirectly by measuring PLN Thr17phosphorylation level. No significant changes were found between the groups. Myofilament Ca(2+) sensitivity is mediated by sarcomeric troponin I (cTnI) phosphorylation. We observed increased unphosphorylated cTnI in PAH compared with donors (P<0.05) and reduced PKA-mediated cTnI phosphorylation (Ser22/23) (P<0.001). Finally, alterations in Ca(2+)-handling proteins contribute to RV diastolic dysfunction due to insufficient diastolic Ca(2+) clearance. PAH SERCA2a levels and PLN phosphorylation were significantly reduced compared with donors (P<0.05).Increased titin stiffness, reduced cTnI phosphorylation, and altered levels of phosphorylation of Ca(2+) handling proteins contribute to RV diastolic dysfunction in PAH.

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Right Ventricular Diastolic Performance in Patients With Chronic Thromboembolic Pulmonary Hypertension Assessed by Echocardiography.

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