Elevated transpulmonary gradient and cardiac magnetic resonance-derived right ventricular remodeling predict poor outcomes in sickle cell disease.
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ABSTRACT:
SUBMITTER: Nguyen KL
PROVIDER: S-EPMC4938326 | biostudies-literature | 2016 Feb
REPOSITORIES: biostudies-literature
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Elevated transpulmonary gradient and cardiac magnetic resonance-derived right ventricular remodeling predict poor outcomes in sickle cell disease.
Nguyen Kim-Lien KL Tian Xin X Alam Shoaib S Mehari Alem A Leung Steve W SW Seamon Catherine C Allen Darlene D Minniti Caterina P CP Sachdev Vandana V Arai Andrew E AE Kato Gregory J GJ
Haematologica 20151120 2
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Project description:BackgroundPulmonary arterial hypertension is usually fatal due to right ventricular failure and is frequently associated with co-existing left ventricular dysfunction. Endothelin-1 is a powerful pro-fibrotic mediator and vasoconstrictor that is elevated in pulmonary arterial hypertension. Endothelin receptor blockers are commonly used as pulmonary vasodilators, however their effect on biventricular injury, remodeling and function, despite elevated isolated right ventricular afterload is unknown.MethodsElevated right ventricular afterload was induced by progressive pulmonary artery banding. Seven rabbits underwent pulmonary artery banding without macitentan; 13 received pulmonary artery banding + macitentan; and 5 did not undergo inflation of the pulmonary artery band (sham-operated controls).ResultsRight and left ventricular collagen content was increased with pulmonary artery banding compared to sham-operated controls and ameliorated by macitentan. Right ventricular fibrosis signaling (connective tissue growth factor and endothelin-1 protein levels); extra-cellular matrix remodeling (matrix-metalloproteinases 2 and 9), apoptosis and apoptosis-related peptides (caspases 3 and 8) were increased with pulmonary artery banding compared with sham-operated controls and decreased with macitentan.ConclusionIsolated right ventricular afterload causes biventricular fibrosis, right ventricular apoptosis and extra cellular matrix remodeling, mediated by up-regulation of endothelin-1 and connective tissue growth factor signaling. These pathological changes are ameliorated by dual endothelin receptor blockade despite persistent elevated right ventricular afterload.
| S-EPMC4713098 | biostudies-literature
Project description:There are limited data on the effects of anthracyclines on right ventricular (RV) structure, function, and tissue characteristics. The goal of this study was to investigate the effects of anthracyclines on the RV using cardiac magnetic resonance (CMR). This was a post-hoc analysis of a prospective study of 27 breast cancer (BC) patients (51.8 ± 8.9 years) using CMR prior, and up to 3-times after anthracyclines (240 mg/m2) to measure RV volumes and mass, RV extracellular volume (ECV) and cardiomyocyte mass (CM). Before anthracyclines, LVEF (69.4 ± 3.6%) and RVEF (55.6 ± 9%) were normal. The median follow-up after anthracyclines was 399 days (IQR 310-517). The RVEF reached its nadir (46.3 ± 6.8%) after 9-months (P < 0.001). RV mass-index and RV CM decreased to 13 ± 2.8 g/m2 and 8.13 ± 2 g/m2, respectively, at 16-months after anthracyclines. The RV ECV expanded from 0.26 ± 0.07 by 0.14 (53%) to 0.40 ± 0.1 (P < 0.001). The RV ECV expansion correlated with a decrease in RV mass-index (r = -0.46; P < 0.001) and the increase in CK-MB. An RV ESV index at baseline above its median predicted an increased risk of LV dysfunction post-anthracyclines. In BC patients treated with anthracyclines, RV atrophy, systolic dysfunction, and a parallel increase of diffuse interstitial fibrosis indicate a cardiotoxic response on a similar scale as previously seen in the systemic left ventricle.
| S-EPMC8385101 | biostudies-literature
Project description:BackgroundPatients with heart failure and left bundle branch block (LBBB) may receive cardiac resynchronization therapy (CRT), but current selection criteria are imprecise, and many patients have limited treatment response. Hemodynamic forces (HDF) have been suggested as a marker for CRT response. The aim of this study was therefore to investigate left ventricular (LV) HDF as a predictive marker for LV remodeling after CRT.MethodsPatients with heart failure, EF < 35% and LBBB (n = 22) underwent CMR with 4D flow prior to CRT. LV HDF were computed in three directions using the Navier-Stokes equations, reported in median N [interquartile range], and the ratio of transverse/longitudinal HDF was calculated for systole and diastole. Transthoracic echocardiography was performed before and 6 months after CRT. Patients with end-systolic volume reduction ≥ 15% were defined as responders.ResultsNon-responders had smaller HDF than responders in the inferior-anterior direction in systole (0.06 [0.03] vs. 0.07 [0.03], p = 0.04), and in the apex-base direction in diastole (0.09 [0.02] vs. 0.1 [0.05], p = 0.047). Non-responders had larger diastolic HDF ratio compared to responders (0.89 vs. 0.67, p = 0.004). ROC analysis of diastolic HDF ratio for identifying CRT non-responders had AUC of 0.88 (p = 0.005) with sensitivity 57% and specificity 100% for ratio > 0.87. Intragroup comparison found higher HDF ratio in systole compared to diastole for responders (p = 0.003), but not for non-responders (p = 0.8).ConclusionHemodynamic force ratio is a potential marker for identifying patients with heart failure and LBBB who are unlikely to benefit from CRT. Larger-scale studies are required before implementation of HDF analysis into clinical practice.
| S-EPMC10463519 | biostudies-literature
Project description:AimsParadoxical low-flow, low-gradient aortic stenosis (pLFLG AS) may represent a diagnostic challenge, and its pathophysiology is complex. While left ventricular (LV) systolic function is preserved, right ventricular dysfunction (RVD) and consecutive LV underfilling may contribute to low-flow and reduced stroke volume index, and to adverse outcomes following transcatheter aortic valve implantation (TAVI). The aim of this study was to evaluate the potential role of RVD in pLFLG AS, and to assess the impact of pre-procedural RVD on clinical outcomes after TAVI in patients with pLFLG AS.Methods and resultsOut of 2739 native AS patients, who received TAVI at the University of Cologne Heart Center between March 2013 and June 2021, 114 patients displayed pLFLG AS and were included in this study. Right ventricular (RV) function was assessed by transthoracic echocardiography, and a fractional area change (FAC) ≤35% and/or a tricuspid annular plane systolic excursion (TAPSE) <18 mm determined RVD. In addition, the TAPSE/systolic pulmonary artery pressure ratio (TAPSE/sPAP) was monitored as a measure of RV-pulmonary arterial (PA) coupling. An impaired FAC and TAPSE was present in 21.9% and 45.6% of patients, respectively, identifying RVD in 50.0%. RVD (p = 0.016), reduced FAC (p = 0.049), reduced TAPSE (p = 0.035) and impaired RV-PA coupling (TAPSE/sPAP ratio <0.31 mm/mmHg; p = 0.009) were associated with significantly higher all-cause mortality compared to patients with normal RV function. After adjustment for sex, age, body mass index, EuroSCORE II, previous myocardial infarction and mitral regurgitation, independent predictors for all-cause mortality were FAC, sPAP, TAPSE/sPAP ratio, right atrial area, RV diameter and tricuspid regurgitation.ConclusionsAdverse RV remodelling, RVD and impaired RV-PA coupling provide an explanation for low-flow and reduced stroke volume index in a subset of patients with pLFLG AS, and are associated with excess mortality after TAVI.
| S-EPMC11659504 | biostudies-literature
Project description:BackgroundThis study retrospectively examined the association between elevated trans-pulmonary gradient (TPG), which reflects pre-capillary contribution to pulmonary hypertension (PH), and postoperative pulmonary hemodynamics and outcomes following restrictive mitral annuloplasty (RMA) in patients with pre-existing PH.MethodsPre- and postoperative (1 month) cardiac catheterization was performed in 64 patients with severely impaired left ventricular function (i.e., ejection fraction ≤40%) and pre-existing PH (mean pulmonary artery pressure (PAP) ≥25 mmHg) who underwent RMA. Patients were segregated into two groups: low TPG (≤12 mmHg) and elevated TPG (>12 mmHg). The mean follow-up period was 54±27 months. The primary outcome seen was a change in pulmonary hemodynamics after RMA; secondary outcomes were composite adverse events, including all-cause mortality and readmission for heart failure.ResultsCompared to the low TPG group, patients in the elevated TPG group were more likely to show a postoperative mean PAP of ≥25 mmHg (84% vs. 38%), TPG of >12 mmHg (79% vs. 11%), and pulmonary vascular resistance of ≥240 dynes/sec/cm-5 (84% vs. 6.7%) (all P<0.001), although both groups showed comparable degrees of mitral regurgitation improvement. Serial echocardiography demonstrated that Doppler-derived systolic PAP, which once decreased in both groups, remained stable in the low group while steadily increasing in the elevated group (group effect P<0.001). Patients with elevated TPG had lower freedom from composite adverse events (5-year, 20% vs. 70%, P=0.003). After adjusting for baseline covariates, the elevated TPG was independently associated with increased risk of adverse events (adjusted hazard ratio 2.9, 95% CI: 1.2-6.9, P=0.017).ConclusionsElevated TPG negatively affects postoperative pulmonary hemodynamics and late outcomes in patients with advanced cardiomyopathy and pre-existing PH who have undergone RMA. These findings suggest that the assessment of TPG should be included in post-RMA risk stratification.
| S-EPMC8182535 | biostudies-literature
Project description:BackgroundAlthough sex differences in heart failure (HF) prevalence and severity have been recognized, its molecular mechanisms are poorly understood. We used a tachycardia-induced cardiomyopathy model to determine the sex specific remodeling pattern in male and female adult pigs.MethodsWe compared the echocardiographic and molecular measures of myocardial remodeling in 19 male and 12 female pigs with chronic symptomatic systolic HF due to right ventricle (RV) pacing (170 bpm) and 6 male and 5 female sham-operated controls. Males achieved subsequent HF stages earlier than females.ResultsThe progression of symptomatic HF was associated with the reduction of the left ventricle (LV) ejection fraction in both sexes (all p < 0.05). A significant LV dilatation occurred only in males (p < 0.001). The HF development was accompanied by an increased pro-hypertrophic factor GATA4 and TGF-β1 messenger RNA (mRNA) expression in the LV only in male pigs (all p < 0.01). The total gelatinolytic activity in LV was higher in males than females (irrespective of HF, p < 0.05), and the HF progression was associated with a reduced total gelatinolytic activity (p < 0.05) in the LV only in males. No differences in LV myocardial collagen content were found between HF groups and sexes. Cardiomyocyte cross-sectional diameter was significantly smaller in male hearts as compared to female (p < 0.05).ConclusionsMale and female porcine hearts respond differently to RV pacing. Males, most likely due to a higher extracellular matrix turnover, demonstrated a significant LV dilatation, followed by a strong induction of pro-hypertrophic program, and an earlier development of symptomatic HF.
| S-EPMC4676102 | biostudies-literature
Project description:AimsTo evaluate whether CMR-derived RV assessment can facilitate risk stratification among patients undergoing transcatheter mitral valve repair (TMVR).BackgroundIn patients undergoing TMVR, only limited data exist regarding the role of RV function. Previous studies assessed the impact of pre-procedural RV dysfunction stating that RV failure may be associated with increased cardiovascular mortality after the procedure.MethodsSixty-one patients underwent CMR, echocardiography and right heart catheterization prior TMVR. All-cause mortality and heart failure hospitalizations were assessed during 2-year follow-up.ResultsAccording to RV ejection fraction (RVEF) <46%, 23 patients (38%) had pre-existing RV dysfunction. By measures of RV end-diastolic volume index (RVEDVi), 16 patients (26%) revealed RV dilatation. Nine patients (15%) revealed both. RV dysfunction was associated with increased right and left ventricular volumes as well as reduced left ventricular (LV) ejection fraction (all p<0.05). During follow-up, 15 patients (25%) died and additional 14 patients (23%) were admitted to hospital due to heart failure symptoms. RV dysfunction predicted all-cause mortality even after adjustment for LV function. Similarly, RVEDVi was a predictor of all-cause mortality even after adjustment for LVEDVi. Kaplan-Meier survival analysis unraveled that, among patients presenting with CMR indicative of both, RV dysfunction and dilatation, the majority (78%) experienced an adverse event during follow-up (p<0.001).ConclusionIn patients undergoing TMVR, pre-existing RV dysfunction and RV dilatation are associated with reduced survival, in progressive additive fashion. The assessment of RV volumes and function by CMR may aid in risk stratification prior TMVR in these high-risk patients.
| S-EPMC7846001 | biostudies-literature
Project description: Not available
| S-EPMC9485656 | biostudies-literature
Project description:BackgroundGlobal indices of right ventricle (RV) function provide limited insights into mechanisms underlying RV remodeling in pulmonary hypertension (PH). While RV myocardial architectural remodeling has been observed in PH, its effect on RV adaptation is poorly understood.MethodsHemodynamic assessments were performed in 2 rodent models of PH. RV free wall myoarchitecture was quantified using generalized Q-space imaging and tractography analyses. Computational models were developed to predict RV wall strains. Data from animal studies were analyzed to determine the correlations between hemodynamic measurements, RV strains, and structural measures.ResultsIn contrast to the PH rats with severe RV maladaptation, PH rats with mild RV maladaptation showed a decrease in helical range of fiber orientation in the RV free wall (139º versus 97º; P=0.029), preserved global circumferential strain, and exhibited less reduction in right ventricular-pulmonary arterial coupling (0.029 versus 0.017 mm/mm Hg; P=0.037). Helical range correlated positively with coupling (P=0.036) and stroke volume index (P<0.01). Coupling correlated with global circumferential strain (P<0.01) and global radial strain (P<0.01) but not global longitudinal strain.ConclusionsData analysis suggests that adaptive RV architectural remodeling could improve RV function in PH. Our findings suggest the need to assess RV architecture within routine screenings of PH patients to improve our understanding of its prognostic and therapeutic significance in PH.
| S-EPMC9974595 | biostudies-literature
Project description:The right ventricle (RV) in hypoplastic left heart syndrome (HLHS) becomes the systemic ventricle pumping against systemic afterload. It also has to adapt to an initially increased volume load followed by a decrease in volume load after Fontan completion. Anatomical HLHS subtype, therapeutic strategy, tricuspid valve regurgitation, recoarctation, and genetics influence RV size and function. The resulting remodeling process can be maladaptive and lead to ventricular systolic and diastolic dysfunction. While systolic dysfunction is a strong predictor for mortality before Fontan, there is increasing evidence for the impact of progressive diastolic dysfunction after Fontan. This comprehensive review summarizes the (recent) empirical observations that increased understanding of RV remodeling and function in HLHS. It aims at clinicians and researchers wishing to increase their understanding of the physiology of this disease. It highlights the potential for future scientific work on the assessment and preservation of myocardial health throughout the palliation.
| S-EPMC11616046 | biostudies-literature