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Abstract Background Balloon pulmonary angioplasty (BPA) improves the prognosis of chronic thromboembolic pulmonary hypertension (CTEPH). Right ventricle (RV) is an important predictor of prognosis in CTEPH patients. 2D-speckle tracking echocardiography (2D-STE) can evaluate RV function. This study aimed to evaluate the effectiveness of BPA in CTEPH patients and to assess the value of 2D-STE in predicting outcomes of BPA. Methods A total of 76 patients with CTEPH underwent 354 BPA sessions from January 2017 to October 2022. Responders were defined as those with mean pulmonary artery pressure (mPAP) ≤ 30 mmHg or those showing ≥ 30% decrease in pulmonary vascular resistance (PVR) after the last BPA session, compared to baseline. Logistic regression analysis was performed to identify predictors of BPA efficacy. Results BPA resulted in a significant decrease in mPAP (from 50.8 ± 10.4 mmHg to 35.5 ± 11.9 mmHg, p

Background: Balloon pulmonary angioplasty (BPA) improves the prognosis of chronic thromboembolic pulmonary hypertension (CTEPH). Right ventricle (RV) is an important predictor of prognosis in CTEPH patients. 2D-speckle tracking echocardiography (2D-STE) can evaluate RV function. This study aimed to evaluate the effectiveness of BPA in CTEPH patients and to assess the value of 2D-STE in predicting outcomes of BPA. Methods: A total of 76 patients with CTEPH underwent 354 BPA sessions from January 2017 to October 2022. Responders were defined as those with mean pulmonary artery pressure (mPAP) ≤ 30 mmHg or those showing ≥ 30% decrease in pulmonary vascular resistance (PVR) after the last BPA session, compared to baseline. Logistic regression analysis was performed to identify predictors of BPA efficacy. Results: BPA resulted in a significant decrease in mPAP (from 50.8 ± 10.4 mmHg to 35.5 ± 11.9 mmHg, p < 0.001), PVR (from 888.7 ± 363.5 dyn·s·cm−5 to 545.5 ± 383.8 dyn·s·cm−5, p < 0.001), and eccentricity index (from 1.3 to 1.1, p < 0.001), and a significant increase in RV free wall longitudinal strain (RVFWLS: from 15.7% to 21.0%, p < 0.001). Significant improvement was also observed in the 6-min walking distance (from 385.5 m to 454.5 m, p < 0.001). After adjusting for confounders, multivariate analysis showed that RVFWLS was the only independent predictor of BPA efficacy. The optimal RVFWLS cutoff value for predicting BPA responders was 12%. Conclusions: BPA was found to reduce pulmonary artery pressure, reverse RV remodeling, and improve exercise capacity. RVFWLS obtained by 2D-STE was an independent predictor of BPA outcomes. Our study may provide a meaningful reference for interventional therapy of CTEPH. [ABSTRACT FROM AUTHOR]

Background: Systemic lupus erythematosus (SLE) is a complex autoimmune connective tissue disease (CTD) that is an important cause of devastating pulmonary arterial hypertension (PAH), and persistent progression of PAH can lead to right heart failure, predicting a poor prognosis for SLE patients. Right ventricular-pulmonary arterial (RV-PA) coupling with echocardiography has been demonstrated to be a noninvasive alternative method for evaluating PAH patients' predictive outcomes. Whether the ratio of right ventricular stroke volume (RVSV) to right ventricular end-systolic volume (RVESV) measured by three-dimensional echocardiography (3DE) is a new index of RV-PA coupling has not been discussed as a new predictor for the clinical outcome of systemic lupus erythematosus-associated pulmonary arterial hypertension (SLE-PAH). Methods: From June 2019 to February 2023, 46 consecutive patients with SLE-PAH were enrolled prospectively, and their clinical data and echocardiographs were studied and analyzed. The control group consisted of 30 healthy subjects matched for age, sex, and body surface area (BSA). The main endpoints of this study were a composite of all-cause mortality and adverse clinical events. Baseline clinical characteristics and echocardiographic assessments were analyzed. Results: During a median of 24 months (IQR 18–31), 16 of 46 SLE-PAH patients (34.7%) experienced endpoint-related events. At baseline, patients who experienced mortality or adverse events had a worse WHO functional class (WHO FC) and lower anti-double-stranded DNA (dsDNA) antibody levels. The right ventricular (RV) systolic dysfunction in SLE-PAH subjects was significantly worse than that in the healthy control group, especially in SLE-PAH patients in the endpoint event group. Compared to controls, patients with SLE-PAH had a lower RVSV/RVESV ratio. In the group comparison, patients who had experienced an endpoint event had a sequentially worse ratio (1.86 (1.65–2.3) versus 1.30 (1.09–1.46) versus 0.64 (0.59-0.67), p <.001). There were statistically significant associations between the RVSV/RVESV ratio to routine RV systolic function and clinical parameters. The RVSV/RVESV ratio was negatively correlated with the WHO FC (r = −0.621, p <.001) and positively correlated with the anti-dsDNA level. The ROC curve showed that the optimal cutoff for RVSV/RVESV < 0.712 determined a higher risk of poor prognosis. Kaplan‒Meier survival curves showed that an RVSV/RVESV ratio >0.712 was associated with more favorable long-term outcomes. Conclusions: The 3DE-derived SV/ESV ratio as a noninvasive alternative surrogate of RV-PA coupling was an eximious indicator for identifying endpoint events in SLE-PAH patients and can provide a diagnostic basis for clinical intervention. [ABSTRACT FROM AUTHOR]

Ferroptosis plays a critical role in pulmonary arterial hypertension (PAH)-induced right ventricular (RV) dysfunction, but key genes remain largely unclear. We here identified HMOX1 as an essential ferroptosis-related differentially expressed gene in PAH by bioinformatic analysis using FerrDb, GSE119754, and GSE3675 datasets, respectively. Notably, there were marked increases in HMOX1 and iron levels in RV of monocrotaline-induced PAH rats with reduced TAPSE levels. More importantly, treatment with ferrostatin-1 effectively attenuated RV hypertrophy, remodeling, myocardial fibrosis, and dysfunction in PAH rats. In cultured H9C2 cells and primary neonatal rat cardiomyocytes, pretreatment with ferrostatin-1 and knockdown HMOX1 by siRNA strikingly blunted hypoxia-induced promotion of lipid peroxidation, ferroptosis, and cardiomyocyte injury by potentiating glutathione (GSH) and nitric oxide signaling, respectively. In summary, ferrostatin-1 attenuates RV hypertrophy, fibrosis, and dysfunction in PAH by suppressing the HMOX1/GSH signaling. Targeting HMOX1 ferroptosis signaling functions as a potential therapeutic strategy for patients with PAH. [ABSTRACT FROM AUTHOR]

Objective: Pulmonary arterial hypertension (PAH) means high blood pressure in the lungs. We aimed to observe the right ventricular size, wall thickness and characteristic functional changes and their associations with PAH in an established model of beagle dogs, and to explore convenient, reliable and sensitive ultrasound indicators for assessing right ventricular remodeling. Methods: Twenty healthy beagle dogs (8-10 kg) were randomly divided into control group (N-dimethylformamide, n = 10) and dehydromonocrotaline (DHMCT) group (DHMCT, n = 10). N-dimethylformamide or DHMCT was injected through a catheter into the right atrium, and then right heart catheterization, routine echocardiography and two-dimensional speckle tracking imaging (2D-STI) were performed before modeling (0 weeks) and 8, 14 weeks after modeling. Hemodynamic parameters and right ventricular function-related ultrasound data were acquired. At the end of the experiment, the animals were killed and the lung tissues were taken for HE staining. Left and right ventricular walls were separated and weighed respectively, and right ventricular hypertrophy index (RVHI) was measured. The associations of the routine ultrasound data and 2D-STI data at each time point with hemodynamic parameters and RVHI were analyzed. Results: At 0, 8 and 14 weeks, gradual decreases in the right ventricular global longitudinal strain (RVLS) were found in DHMCT group. RVH occurred in DHMCT group, and DHMCT group had a significantly higher RVHI than that of control group (49.83 ± 4.83% vs. 39.80 ± 1.40%, P < .001) and larger pulmonary artery media thickness. RVLS had significant positive correlations with RVSP (r = 0.74, P < .001), mRVP (r = 0.72, P < .001), PASP (r = 0.75, P < .001), mPAP (r = 0.72, P < .001) and PVR (r = 0.68, P < .001). There was a significant positive correlation between RVLS and RVHI (r = 0.74, P < .001). Conclusion: The right ventricular function in PAH can be effectively assessed by echocardiography, and RVLS measured by 2D-STI sensitively reflects right ventricular remodeling following PAH. [ABSTRACT FROM AUTHOR]

Healthy aging has been associated with alterations in pulmonary vascular and right ventricular (RV) hemodynamics, potentially leading to RV remodeling. Despite the current evidence suggesting an association between aging and alterations in RV function and higher prevalence of pulmonary hypertension in the elderly, limited data exist on age-related differences in RV structure and biomechanics. In this work, we report our preliminary findings on the effects of healthy aging on RV structure, function, and biomechanical properties. Hemodynamic measurements, biaxial mechanical testing, constitutive modeling, and quantitative transmural histological analysis were employed to study two groups of male Sprague-Dawley rats: control (11 weeks) and aging (80 weeks). Aging was associated with increases in RV peak pressures (+17%, p = 0.017), RV contractility (+52%, p = 0.004), and RV wall thickness (+38%, p = 0.001). Longitudinal realignment of RV collagen (16.4°, p = 0.013) and myofibers (14.6°, p = 0.017) were observed with aging, accompanied by transmural cardiomyocyte loss and fibrosis. Aging led to increased RV myofiber stiffness (+141%, p = 0.003), in addition to a bimodal alteration in the biaxial biomechanical properties of the RV free wall, resulting in increased tissue-level stiffness in the low-strain region, while progressing into decreased stiffness at higher strains. Our results demonstrate that healthy aging may modulate RV remodeling via increased peak pressures, cardiomyocyte loss, fibrosis, fiber reorientation, and altered mechanical properties in male Sprague-Dawley rats. Similarities were observed between aging-induced remodeling patterns and those of RV remodeling in pressure overload. These findings may help our understanding of age-related changes in the cardiovascular fitness and response to disease.

Aims Iron deficiency is common in pulmonary hypertension, but its clinical significance and optimal definition remain unclear. Methods and results Phenotypic data for 1028 patients enrolled in the Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics study were analyzed. Iron deficiency was defined using the conventional heart failure definition and also based upon optimal cut-points associated with impaired peak oxygen consumption (peakVO2), 6-min walk test distance, and 36-Item Short Form Survey (SF-36) scores. The relationships between iron deficiency and cardiac and pulmonary vascular function and structure and outcomes were assessed. The heart failure definition of iron deficiency endorsed by pulmonary hypertension guidelines did not identify patients with reduced peakVO2, 6-min walk test, and SF-36 (P > 0.208 for all), but defining iron deficiency as transferrin saturation (TSAT) <21% did. Compared to those with TSAT ≥21%, patients with TSAT <21% demonstrated lower peakVO2 [absolute difference: −1.89 (−2.73 to −1.04) mL/kg/min], 6-min walk test distance [absolute difference: −34 (−51 to −17) m], and SF-36 physical component score [absolute difference: −2.5 (−1.3 to −3.8)] after adjusting for age, sex, and hemoglobin (all P < 0.001). Patients with a TSAT <21% had more right ventricular remodeling on cardiac magnetic resonance but similar pulmonary vascular resistance on catheterization. Transferrin saturation <21% was also associated with increased mortality risk (hazard ratio 1.63, 95% confidence interval 1.13–2.34; P = 0.009) after adjusting for sex, age, hemoglobin, and N-terminal pro-B-type natriuretic peptide. Conclusion The definition of iron deficiency in the 2022 European Society of Cardiology (ESC)/European Respiratory Society (ERS) pulmonary hypertension guidelines does not identify patients with lower exercise capacity or functional status, while a definition of TSAT <21% identifies patients with lower exercise capacity, worse functional status, right heart remodeling, and adverse clinical outcomes. [ABSTRACT FROM AUTHOR]

BackgroundPulmonary hypertension (PH) results in increased right ventricular (RV) afterload and ventricular remodeling. Sacubitril/valsartan (sac/val) is a dual acting drug, composed of the neprilysin inhibitor sacubitril and the angiotensin receptor blocker valsartan, that has shown promising outcomes in reducing the risk of death and hospitalization for chronic systolic left ventricular heart failure. In this study, we aimed to examine if angiotensin receptor-neprilysin inhibition using sac/val attenuates RV remodeling in PH.Methods and ResultsRV pressure overload was induced in Sprague-Dawley rats via banding the main pulmonary artery. Three different cohorts of controls, placebo-treated PH, and sac/val-treated PH were studied in a 21-day treatment window. Terminal invasive hemodynamic measurements, quantitative histological analysis, biaxial mechanical testing, and constitutive modeling were employed to conduct a multiscale analysis on the effects of sac/val on RV remodeling in PH. Sac/val treatment decreased RV maximum pressures (29% improvement, P=0.002), improved RV contractile (30%, P=0.012) and relaxation (29%, P=0.043) functions, reduced RV afterload (35% improvement, P=0.016), and prevented RV-pulmonary artery uncoupling. Furthermore, sac/val attenuated RV hypertrophy (16% improvement, P=0.006) and prevented transmural reorientation of RV collagen and myofibers (P=0.011). The combined natriuresis and vasodilation resulting from sac/val led to improved RV biomechanical properties and prevented increased myofiber stiffness in PH (61% improvement, P=0.032).ConclusionsSac/val may prevent maladaptive RV remodeling in a pressure overload model via amelioration of RV pressure rise, hypertrophy, collagen, and myofiber reorientation as well as tissue stiffening both at the tissue and myofiber level.

BackgroundPulmonary hypertension (PH) results in increased right ventricular (RV) afterload and ventricular remodeling. Sacubitril/valsartan (sac/val) is a dual acting drug, composed of the neprilysin inhibitor sacubitril and the angiotensin receptor blocker valsartan, that has shown promising outcomes in reducing the risk of death and hospitalization for chronic systolic left ventricular heart failure. In this study, we aimed to examine if angiotensin receptor-neprilysin inhibition using sac/val attenuates RV remodeling in PH.Methods and ResultsRV pressure overload was induced in Sprague-Dawley rats via banding the main pulmonary artery. Three different cohorts of controls, placebo-treated PH, and sac/val-treated PH were studied in a 21-day treatment window. Terminal invasive hemodynamic measurements, quantitative histological analysis, biaxial mechanical testing, and constitutive modeling were employed to conduct a multiscale analysis on the effects of sac/val on RV remodeling in PH. Sac/val treatment decreased RV maximum pressures (29% improvement, P=0.002), improved RV contractile (30%, P=0.012) and relaxation (29%, P=0.043) functions, reduced RV afterload (35% improvement, P=0.016), and prevented RV-pulmonary artery uncoupling. Furthermore, sac/val attenuated RV hypertrophy (16% improvement, P=0.006) and prevented transmural reorientation of RV collagen and myofibers (P=0.011). The combined natriuresis and vasodilation resulting from sac/val led to improved RV biomechanical properties and prevented increased myofiber stiffness in PH (61% improvement, P=0.032).ConclusionsSac/val may prevent maladaptive RV remodeling in a pressure overload model via amelioration of RV pressure rise, hypertrophy, collagen, and myofiber reorientation as well as tissue stiffening both at the tissue and myofiber level.

Abstract Background Hypoxia-induced pulmonary hypertension (HPH) is one of the fatal pathologies developed under hypobaric hypoxia and eventually leads to right ventricular (RV) remodeling and RV failure. Clinically, the mortality rate of RV failure caused by HPH is high and lacks effective drugs. Xinyang Tablet (XYT), a traditional Chinese medicine exhibits significant efficacy in the treatment of congestive heart failure and cardiac dysfunction. However, the effects of XYT on chronic hypoxia-induced RV failure are not clear. Methods The content of XYT was analyzed by high-performance liquid chromatography-tandem mass spectrometry (HPLC–MS). Sprague–Dawley (SD) rats were housed in a hypobaric chamber (equal to the parameter in altitude 5500 m) for 21 days to obtain the RV remodeling model. Electrocardiogram (ECG) and hemodynamic parameters were measured by iWorx Acquisition & Analysis System. Pathological morphological changes in the RV and pulmonary vessels were observed by H&E staining and Masson’s trichrome staining. Myocardial apoptosis was tested by TUNEL assay. Protein expression levels of TNF-α, IL-6, Bax, Bcl-2, and caspase-3 in the RV and H9c2 cells were detected by western blot. Meanwhile, H9c2 cells were induced by CoCl2 to establish a hypoxia injury model to verify the protective effect and mechanisms of XYT. A CCK-8 assay was performed to determine the viability of H9c2 cells. CoCl2-induced apoptosis was detected by Annexin-FITC/PI flow cytometry and Hoechst 33,258 staining. Results XYT remarkably improved RV hemodynamic disorder and ECG parameters. XYT attenuated hypoxia-induced pathological injury in RV and pulmonary vessels. We also observed that XYT treatment decreased the expression levels of TNF-α, IL-6, Bax/Bcl-2 ratio, and the numbers of myocardial apoptosis in RV. In H9c2 myocardial hypoxia model, XYT protected H9c2 cells against Cobalt chloride (CoCl2)-induced apoptosis. We also found that XYT could antagonize CoCl2-induced apoptosis through upregulating Bcl-2, inhibiting Bax and caspase-3 expression. Conclusions We concluded that XYT improved hypoxia-induced RV remodeling and protected against cardiac injury by inhibiting apoptosis pathway in vivo and vitro models, which may be a promising therapeutic strategy for clinical management of hypoxia-induced cardiac injury.

This study reports a new methodology for right heart imaging by ultrasound in mice under right ventricular (RV) pressure overload. Pulmonary artery constriction (PAC) or sham surgeries were performed on C57BL/6 male mice at 8 wk of age. Ultrasound imaging was conducted at 2, 4, and 8 wk postsurgery using both classical and advanced ultrasound imaging modalities including electrocardiogram (ECG)-based kilohertz visualization, anatomical M-mode, and strain imaging. Based on pulsed Doppler, the PAC group demonstrated dramatically enhanced pressure gradient in the main pulmonary artery (MPA) as compared with the sham group. By the application of advanced imaging modalities in novel short-axis views of the ventricles, the PAC group demonstrated increased thickness of RV free wall, enlarged RV chamber, and reduced RV fractional shortening compared with the sham group. The PAC group also showed prolonged RV contraction, asynchronous interplay between RV and left ventricle (LV), and passive leftward motion of the interventricular septum (IVS) at early diastole. Consequently, the PAC group exhibited prolongation of LV isovolumic relaxation time, without change in LV wall thickness or systolic function. Significant correlations were found between the maximal pressure gradient in MPA measured by Doppler and the RV systolic pressure by catheterization, as well as the morphological and functional parameters of RV by ultrasound. [ABSTRACT FROM AUTHOR]

Background: Right ventricular (RV) function is a major prognostic factor in patients with cardiopulmonary disease. Effective medical therapies are available for left heart failure, but they are usually less effective or even ineffective in right heart failure. Here, we tested the hypothesis that LCZ696 (sacubitril/valsartan) can attenuate pressure overload-induced RV remodeling by inhibiting pyruvate dehydrogenase kinase 4 (PDK4). Methods: Adult male C57 mice were subjected to transverse aortic constriction (TAC), pulmonary artery constriction (PAC), or sham surgery. Bioinformatics analysis was used to screen for common differentially expressed genes (DEGs) between TAC and PAC. Chemical compounds targeting DEGs were predicted by molecular docking analysis. Effects of LCZ696 on PAC-induced RV remodeling and the associated PDK4-related mechanisms were investigated. Results: We found 60 common DEGs between PAC and TAC, and Pdk4 was one of the downregulated DEGs. From 47 chemical compounds with potential cardiovascular activity and PDK4 protein binding ability, we selected LCZ696 to treat PAC-induced RV remodeling because of its high docking score for binding PDK4. Compared with vehicle-treated PAC mice, LCZ696-treated mice had significantly smaller RV wall thickness and RV diameters, less myocardial fibrosis, lower expression of PDK4 protein, and less phosphorylation of glycogen synthase kinase-3β (p-GSK3β). In PAC mice, overexpression of Pdk4 blocked the inhibitory effect of LCZ696 on RV remodeling, whereas conditional knockout of Pdk4 attenuated PAC-induced RV remodeling. Conclusions: Pdk4 is a common therapeutic target for pressure overload-induced left ventricular and RV remodeling, and LCZ696 attenuates RV remodeling by downregulating Pdk4 and inhibiting PDK4/p-GSK3β signal.

Abstract Background Whether cigarette smoking affects the heart post-myocardial infarction (MI) in a sex-dependent way remains controversial. Using a mouse model, we investigated cardiac remodeling under the influence of acute cigarette smoke (CS) exposure following ischemic injury in both sexes. Methods Ten cigarettes were smoked twice daily for 2 weeks followed by MI and then 1 additional week post permanent LAD ligation. Cardiac function, histology, and infarct size were assessed, and inflammatory markers quantified by RT–PCR. Statistical comparisons were performed using an unpaired t test or ANOVA followed by Tukey post hoc test. Results We observed that cigarette smoking exacerbated both left and right ventricular remodeling only in males at an early stage of post-MI. Females did not display a significant structural and/or functional alteration within 7 days of cardiac remodeling post-MI upon CS exposure. Worsened right ventricular remodeling in males was independent of pulmonary congestion. CS-exposed males exhibited enhanced increases in left ventricular end systolic and diastolic volumes, as well as reductions in ejection fraction and fractional area changes of left ventricular base. At day 7, infarct size was increased by cigarette smoking in males only, which was accompanied by enhanced collagen deposition in both the infarcted and peri-infarcted areas. Both IL-6 and TNF-α mRNA expression significantly increased in CS-exposed MI male group only at day 7 post-MI suggestive of prolonged inflammation. Conclusions These findings indicate that CS exposure worsens the progression of cardiac remodeling post-MI in male sex in a significant manner compared to female sex at least at early stages.

Background: Hypoxia-induced pulmonary hypertension (HPH) is one of the fatal pathologies developed under hypobaric hypoxia and eventually leads to right ventricular (RV) remodeling and RV failure. Clinically, the mortality rate of RV failure caused by HPH is high and lacks effective drugs. Xinyang Tablet (XYT), a traditional Chinese medicine exhibits significant efficacy in the treatment of congestive heart failure and cardiac dysfunction. However, the effects of XYT on chronic hypoxia-induced RV failure are not clear. Methods: The content of XYT was analyzed by high-performance liquid chromatography-tandem mass spectrometry (HPLC–MS). Sprague–Dawley (SD) rats were housed in a hypobaric chamber (equal to the parameter in altitude 5500 m) for 21 days to obtain the RV remodeling model. Electrocardiogram (ECG) and hemodynamic parameters were measured by iWorx Acquisition & Analysis System. Pathological morphological changes in the RV and pulmonary vessels were observed by H&E staining and Masson's trichrome staining. Myocardial apoptosis was tested by TUNEL assay. Protein expression levels of TNF-α, IL-6, Bax, Bcl-2, and caspase-3 in the RV and H9c2 cells were detected by western blot. Meanwhile, H9c2 cells were induced by CoCl2 to establish a hypoxia injury model to verify the protective effect and mechanisms of XYT. A CCK-8 assay was performed to determine the viability of H9c2 cells. CoCl2-induced apoptosis was detected by Annexin-FITC/PI flow cytometry and Hoechst 33,258 staining. Results: XYT remarkably improved RV hemodynamic disorder and ECG parameters. XYT attenuated hypoxia-induced pathological injury in RV and pulmonary vessels. We also observed that XYT treatment decreased the expression levels of TNF-α, IL-6, Bax/Bcl-2 ratio, and the numbers of myocardial apoptosis in RV. In H9c2 myocardial hypoxia model, XYT protected H9c2 cells against Cobalt chloride (CoCl2)-induced apoptosis. We also found that XYT could antagonize CoCl2-induced apoptosis through upregulating Bcl-2, inhibiting Bax and caspase-3 expression. Conclusions: We concluded that XYT improved hypoxia-induced RV remodeling and protected against cardiac injury by inhibiting apoptosis pathway in vivo and vitro models, which may be a promising therapeutic strategy for clinical management of hypoxia-induced cardiac injury. [ABSTRACT FROM AUTHOR]

Abstract Background We aimed to establish the relationships between the expression of microRNAs (miRNAs) and echocardiographic right ventricular (RV) function parameters, and to explore the effectiveness and clinical value of miRNA expression in predicting RV injury and dysfunction in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Methods In this retrospective study, clinical data were collected from eight CTEPH patients and eight healthy individuals. RV parameters on echocardiography were analyzed, and the expression levels of specific miRNAs were measured by quantitative real-time PCR. Correlation analysis was performed on structural and functional RV parameters and five candidate miRNAs (miR-20a-5p, miR-17-5p, miR-93-5p, miR-3202 and miR-665). The diagnostic value of RV functional parameters and miRNAs expression was assessed by receiver operating characteristic (ROC) curve analysis and C statistic. Results Among the tested miRNAs, miR-20a-5p expression showed the best correlation with echocardiographic RV functional parameters (P

BackgroundRight heart remodeling occurs in a substantial proportion of patients with chronic thromboembolic pulmonary hypertension (CTEPH) and significantly affects their prognosis. Two-dimensional speckle-tracking echocardiography (2D-STE) can be used to evaluate myocardial deformation under physiological and pathological conditions. This study aimed to assess the feasibility of 2D-STE for evaluating right ventricular (RV) remodeling in CTEPH patients.MethodsThis retrospective study included 21 CTEPH patients who underwent transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR). Data for the following parameters that can reflect RV function were collected: tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), right ventricular index of myocardial performance (RIMP), peak systolic velocity of the tricuspid annulus (S'), and CMR-right ventricular ejection fraction (CMR-RVEF). The following strain parameters were calculated using post-processing software: STE-RV global longitudinal strain (STE-RVGLS), STE-RV free wall longitudinal strain (STE-RVFWLS), and CMR-RVGLS.ResultsAs CMR-RVEF deteriorated, RV remodeling in CTEPH patients became more apparent and was mainly characterized by significant enlargement of the RV, weakening of myocardial deformation, and a decrease in RV contractility (RV area, STE-RVFWLS, STE-RVGLS: mild vs. severe and moderate vs. severe, p < 0.05; CMR-RVGLS: mild vs. severe, p < 0.05; TAPSE: moderate vs. severe, p < 0.05). Moreover, the Pearson correlation coefficient for correlation with CMR-derived RVEF was stronger for RVFWLS than for CMR-GLS (r-value: 0.70 vs. 0.68), and the strain values measured by 2D-STE showed a weak correlation with right heart catheterization data. Bland-Altman analysis showed good agreement between 2D-STE and CMR-feature tracking (FT) for RVGLS (bias = −0.96; 95% limit of agreement from −8.42 to 6.49).ConclusionsFor the measurement of RVGLS, 2D-STE is similarly feasible to CMR-FT and could sensitively identify right heart remodeling.

Pulmonary arterial hypertension (PAH) is a progressive condition that frequently leads to right ventricular (RV) remodeling. Aldosterone promotes vascular and RV remodeling. The upregulation of steroidogenic acute regulatory protein (StAR) stimulates aldosterone synthesis. However, the expression of StAR in the myocardium under PAH conditions remains unknown. To investigate the expression of StAR in the myocardium and its association with RV remodeling in PAH, utilizing spironolactone as a treatment. A PAH model was created using male Sprague-Dawley rats, which received a subcutaneous injection of Sugen5416 (20 mg/kg) and were exposed to hypoxia (10% O 2 ) for 2 weeks, followed by 2 weeks of normoxia. The animals were then divided into two groups, with one group receiving spironolactone (25 mg/kg/day) for an additional 4 weeks, while the other group did not. H9c2 cells were cultured under hypoxic conditions (37 °C, 1% O 2 , 5% CO 2 ) with or without spironolactone treatment. In the model rats, RV systolic pressure and the Fulton index, both of which increased upon exposure to Sugen5416 and hypoxia, significantly decreased with spironolactone treatment. In H9c2 cells, hypoxic exposure elevated aldosterone levels, while spironolactone treatment significantly suppressed aldosterone production. Suppression of StAR expression in the myocardium via spironolactone contributes to the improvement of RV remodeling in PAH. Spironolactone may offer a valuable therapeutic strategy for RV remodeling in patients with PAH., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Clinically significant tricuspid regurgitation (TR) is common and associated with excess mortality. At the same time right ventricular (RV) failure is a complex clinical syndrome that results from many causes, but is often associated with long-term prognosis. Whilst results of isolated tricuspid valve (TV) surgery are often unsatisfactory and limited by the prohibitive risk of most patients, the recent development of percutaneous recovery techniques has opened new scenarios. In consideration of the complexity of the mechanisms that lead to right heart failure and RV dysfunction it is important to understand the real advantages that percutaneous TV treatment can offer, more specifically the effect of TR reduction on RV remodeling in the setting of functional tricuspid regurgitation (fTR).

Background: Whether cigarette smoking affects the heart post-myocardial infarction (MI) in a sex-dependent way remains controversial. Using a mouse model, we investigated cardiac remodeling under the influence of acute cigarette smoke (CS) exposure following ischemic injury in both sexes. Methods: Ten cigarettes were smoked twice daily for 2 weeks followed by MI and then 1 additional week post permanent LAD ligation. Cardiac function, histology, and infarct size were assessed, and inflammatory markers quantified by RT–PCR. Statistical comparisons were performed using an unpaired t test or ANOVA followed by Tukey post hoc test. Results: We observed that cigarette smoking exacerbated both left and right ventricular remodeling only in males at an early stage of post-MI. Females did not display a significant structural and/or functional alteration within 7 days of cardiac remodeling post-MI upon CS exposure. Worsened right ventricular remodeling in males was independent of pulmonary congestion. CS-exposed males exhibited enhanced increases in left ventricular end systolic and diastolic volumes, as well as reductions in ejection fraction and fractional area changes of left ventricular base. At day 7, infarct size was increased by cigarette smoking in males only, which was accompanied by enhanced collagen deposition in both the infarcted and peri-infarcted areas. Both IL-6 and TNF-α mRNA expression significantly increased in CS-exposed MI male group only at day 7 post-MI suggestive of prolonged inflammation. Conclusions: These findings indicate that CS exposure worsens the progression of cardiac remodeling post-MI in male sex in a significant manner compared to female sex at least at early stages. [ABSTRACT FROM AUTHOR]

Objective To evaluate the effect of Riociguat on the right ventricular remodeling and function in the patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension(CTEPH). Methods Embase, PubMed, Cochrane Library, China national knowledge infrastructure(CNKI) and Wanfang databases were searched, to collect the relevant studies of right ventricular remodeling and right ventricular function of pulmonary hypertension by Riociguat reversal. The quality evaluation was performed independently by two reviewers. After the data extraction, the meta analysis was performed by using the RevMan5.3software.Results A total of five non-randomized controlled trials involving 186patients were included, including three prospective observational studies and two retrospective studies. The meta-analysis showed that Riociguat could significantly increase 6-minutes walking distance and improve pulmonary hemodynamics. In addition, after taking Riociguat, the right atrium area and right ventricle basal diameter reduced, right ventricular fractional area change and tricuspid annular plane systolic excursion increased, the differences were statistically significant(P<0.01). Conclusion Riociguat can improve the pulmonary hemodynamics, reverse right ventricular remodeling and improve the right ventricular function in the patients with PAH and CTEPH. However, more randomized controlled studies with large samples are needed to further verify the effect of Riociguat on the right ventricular remodeling and function. [ABSTRACT FROM AUTHOR]

Background: Congenital shunt location is related to Eisenmenger syndrome (ES) survival. Moreover, right ventricular (RV) remodeling is associated with poor survival in pulmonary hypertension. Purpose: To investigate RV remodeling using comprehensive magnetic resonance imaging (MRI) techniques and identify its relationship with prognosis in ES subgroups classified by shunt location. Study Type: Prospective observational study. Population: Fifty‐four adults with ES (16 with pre‐tricuspid shunt and 38 with post‐tricuspid shunt). Field Strength/Sequence: 3.0 T/cine MRI with balanced steady‐state free precession sequence, late gadolinium enhancement with inversion recovery segmented gradient echo sequence and phase‐sensitive reconstruction, and T1 mapping with modified Look‐Locker inversion recovery sequence. Assessment: Demographics, clinical characteristics, hemodynamics, RV remodeling features (morphology, systolic function, RV–pulmonary artery (PA) coupling and myocardial fibrosis), and prognosis were compared between ES subgroups. The adverse endpoint was all‐cause mortality or readmission for heart failure. Statistical Tests: The independent samples t‐test, Fisher's exact test or Chi‐squared test, and the Kaplan–Meier method were used. P < 0.05 was considered significant. Results: Compared to patients with post‐tricuspid shunt, patients with pre‐tricuspid shunt were significantly older and had higher N‐terminal pro‐B‐type natriuretic peptide concentrations and poorer exercise tolerance. Pre‐tricuspid shunt showed significantly larger RV dimensions (end‐diastolic volume index: 185.81 ± 37.49 vs. 98.20 ± 36.26 mL/m2), worse RV ejection fraction (23.54% ± 12.35% vs. 40.82% ± 10.77%), and RV–PA decoupling (0.35 ± 0.31 vs. 0.72 ± 0.29). Biventricular myocardial fibrosis was significantly more severe in pre‐tricuspid shunt than post‐tricuspid shunt (extracellular volume, left ventricle: 35.85% ± 2.58% vs. 29.10% ± 5.20%; RV free wall: 30.93% ± 5.65% vs. 26.75% ± 5.15%). In addition, pre‐tricuspid shunt demonstrated a significantly increased risk of adverse endpoint (hazard ratio: 2.938, 95% confidence interval: 1.204–7.172). Data Conclusion: ES with pre‐tricuspid shunt might be a unique subtype with worse clinically decompensated RV remodeling and poor prognosis. Level of Evidence: 2 Technical Efficacy Stage: 5 [ABSTRACT FROM AUTHOR]

Abstract Background Right ventricular (RV) free wall fibrosis is an important component of adverse remodeling with RV dysfunction in pulmonary hypertension (PH). However, no previous reports have compared cardiovascular magnetic resonance (CMR) findings and histological analysis for RV free wall fibrosis in PH. We aimed to assess the feasibility of CMR T1 mapping with extracellular volume fraction (ECV) for evaluating the progression of RV free wall fibrosis in PH, and compared imaging findings to histological collagen density through an animal study. Methods Among 42 6-week-old Wistar male rats, 30 were classified according to disease duration (baseline before monocrotaline injection, and 2, 4, 6 and 8 weeks after injection) and 12 were used to control for aging (4 and 8 weeks after the baseline). We obtained pre and post-contrast T1 maps for native T1 and ECV of RV and left ventricular (LV) free wall for six animals in each disease-duration group. Collagen density of RV free wall was calculated with Masson's trichrome staining. The Kruskall-Wallis test was performed to compare the groups. Native T1 and ECV to collagen density were analyzed with Spearman’s correlation. Results The mean values of native T1, ECV and collagen density of the RV free wall at baseline were 1541 ± 33 ms, 17.2 ± 1.3%, and 4.7 ± 0.5%, respectively. The values of RV free wall did not differ according to aging (P = 0.244, 0.504 and 0.331, respectively). However, the values significantly increased according to disease duration (P

IntroductionSevere tricuspid regurgitation (TR) is a common condition promoting right heart failure and is associated with a poor long-term prognosis. Transcatheter tricuspid valve repair (TTVR) emerged as a low-risk alternative to surgical repair techniques. However, patient selection remains controversial, particularly regarding the benefits of TTVR in patients with pulmonary hypertension (PH).AimWe aimed to investigate the impact of preprocedural invasive hemodynamic assessment and procedural success on right ventricular (RV) remodeling and outcome.MethodsAll patients undergoing TTVR with a TR reduction of ≥1 grade without precapillary or combined PH [mean pulmonary artery pressure (mPAP) ≥25 mmHg, mean pulmonary artery Wedge pressure ≤ 15 mmHg, pulmonary vascular resistance ≥3 Wood units] were assigned to the responder group. All patients with a TR reduction of ≥1 grade and precapillary or combined PH were classified as non-responders. Patients with a TR reduction ≥2 grade were directly classified as responders, and patients without TR reduction were directly assigned as non-responders.ResultsA total of 107 patients were enrolled, 75 were classified as responders and 32 as non-responders. We observed evidence of significant RV reverse remodeling in responders with a decrease in RV diameters (−2.9 mm, p = 0.001) at a mean follow-up of 229 days (±219 SD) after TTVR. RV function improved in responders [fractional area change (FAC) + 5.7%, p < 0.001, RV free wall strain +3.9%, p = 0.006], but interestingly further deteriorated in non-responders (FAC −4.5%, p = 0.003, RV free wall strain −3.9%, p = 0.007). Non-responders had more persistent symptoms than responders (NYHA ≥3, 72% vs. 11% at follow-up). Subsequently, non-response was associated with a poor long-term prognosis in terms of death, heart failure (HF) hospitalization, and re-intervention after 2 years (freedom of death, HF hospitalization, and reintervention at 2 years: 16% vs. 78%, log-rank: p < 0.001).ConclusionHemodynamic assessment before TTVR and procedural success are significant factors for patient prognosis. The hemodynamic profiling prior to intervention is an essential component in patient selection for TTVR. The window for edge-to-edge TTVR might be limited, but timely intervention is an important factor for a better outcome and successful right ventricular reverse remodeling.

Introductionambrisentan and phosphodiesterase type 5 inhibitor (PDE5i) have been approved for treating patients with pulmonary arterial hypertension (PAH). Echocardiographic right ventricular pulmonary artery coupling (RVPAC) has been shown to be a valid non-invasive and alternative measurement method to assess the predicted outcomes in PAH patients. The aim of this study was to study the effect and clinical correlates of initial ambrisentan plus PDE5i combination therapy on RVPAC in patients with severe PAH.Method and ResultsWe retrospectively studied and analyzed comprehensive clinical data, hemodynamics, and echocardiography in 27 patients with severe PAH before and after 6 months of initial combination therapy. Compared with the baseline, significant improvements in RVPAC ratios were observed, including RVFAC/PASP (0.31 ± 0.10 vs. 0.44 ± 0.15%/mmHg, p < 0.001), TAPSE/PASP (0.15 ± 0.05 vs. 0.21 ± 0.06 mm/mmHg, p = 0.001), S’/PASP (0.10 ± 0.03 vs. 0.14 ± 0.05 cm/s∙mmHg, p = 0.001), and RVSV/RVESV (0.79 ± 0.22 vs. 1.02 ± 0.20, p < 0.001). Functional status indices [World Health Organization functional classifications (WHO-FC) and 6 min walk distance (6MWD) and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels] showed significant improvements. Right heart catheterization (RHC) evaluations for hemodynamic measurements between baseline and the 6–12 month follow-up were sPAP (96 ± 22 vs. 86 ± 24 mmHg, p = 0.002), mPAP (64 ± 18 vs. 56 ± 17 mmHg, p < 0.001) and TPVR (17.3 ± 6.7 vs. 12.1 ± 5.4 WU, p = 0.001). Simultaneously, significant associations between RVPAC ratios and NT-proBNP levels and WHO-FC and 6MWD were observed.ConclusionAmbrisentan plus PDE-5i combination therapy resulted in a significant improvement in RVPAC in severe PAH. Importantly, RVPAC parameters correlated with known prognostic markers of PAH.

Abstract Background Studies on the management of functional tricuspid regurgitation (TR) during mitral valve operations have drawn inconsistent conclusions. This study was designed to compare the treatment strategy of concomitant tricuspid annuloplasty (TAP) against isolated mitral valve replacement (MVR) in rheumatic mitral valve disease patients, and to assess the effect of concomitant TAP on postoperative right ventricular (RV) remodeling and function. Methods One hundred-seventy patients with rheumatic mitral valve disease receiving MVR were categorized into TAP group (n = 124) and non-TAP group (n = 46). Clinical and echocardiographic data were collected preoperatively and at 1-year follow-up. Three-dimensional echocardiographic indices of RV geometry and function were analyzed. Results At baseline, concomitant TAP group had larger RV end-diastolic volume, more decreased RV ejection fraction and RV longitudinal strain than non-TAP group (all P

Background: We aimed to establish the relationships between the expression of microRNAs (miRNAs) and echocardiographic right ventricular (RV) function parameters, and to explore the effectiveness and clinical value of miRNA expression in predicting RV injury and dysfunction in patients with chronic thromboembolic pulmonary hypertension (CTEPH).Methods: In this retrospective study, clinical data were collected from eight CTEPH patients and eight healthy individuals. RV parameters on echocardiography were analyzed, and the expression levels of specific miRNAs were measured by quantitative real-time PCR. Correlation analysis was performed on structural and functional RV parameters and five candidate miRNAs (miR-20a-5p, miR-17-5p, miR-93-5p, miR-3202 and miR-665). The diagnostic value of RV functional parameters and miRNAs expression was assessed by receiver operating characteristic (ROC) curve analysis and C statistic.Results: Among the tested miRNAs, miR-20a-5p expression showed the best correlation with echocardiographic RV functional parameters (P < 0.05), although the expression levels of miR-93-5p, miR-17-5p and miR-3202 showed positive associations with some RV parameters. ROC curve analysis demonstrated the ability of miR-20a-5p expression to predict RV dysfunction, with a maximum area under the curve of 0.952 (P = 0.003) when the predicted RV longitudinal strain was less than -20%. The C index for RV dysfunction prediction by the combination of miRNAs (miR-20a-5p, miR-93-5p and miR-17-5p) was 1.0, which was significantly larger than the values for miR-93-5p and miR-17-5p individually (P = 0.0337 and 0.0453, respectively).Conclusion: Among the tested miRNAs, miR -20a-5p, miR -93-5p and miR -17-5p have potential value in the diagnosis of CTEPH based on the correlation between the abnormal expression of these miRNAs and echocardiographic parameters in CTEPH patients. miR-20a-5p showed the strongest correlation with echocardiographic RV functional parameters. Moreover, expression of a combination of miRNAs seemed to show excellent predictive power for RV dysfunction. [ABSTRACT FROM AUTHOR]

Healthy aging has been associated with alterations in pulmonary vascular and right ventricular (RV) hemodynamics, potentially leading to RV remodeling. Despite the current evidence suggesting an association between aging and alterations in RV function and higher prevalence of pulmonary hypertension in the elderly, limited data exist on age-related differences in RV structure and biomechanics. In this work, we report our preliminary findings on the effects of healthy aging on RV structure, function, and biomechanical properties. Hemodynamic measurements, biaxial mechanical testing, constitutive modeling, and quantitative transmural histological analysis were employed to study two groups of male Sprague-Dawley rats: control (11 weeks) and aging (80 weeks). Aging was associated with increases in RV peak pressures (+17%, p = 0.017), RV contractility (+52%, p = 0.004), and RV wall thickness (+38%, p = 0.001). Longitudinal realignment of RV collagen (16.4°, p = 0.013) and myofibers (14.6°, p = 0.017) were observed with aging, accompanied by transmural cardiomyocyte loss and fibrosis. Aging led to increased RV myofiber stiffness (+141%, p = 0.003), in addition to a bimodal alteration in the biaxial biomechanical properties of the RV free wall, resulting in increased tissue-level stiffness in the low-strain region, while progressing into decreased stiffness at higher strains. Our results demonstrate that healthy aging may modulate RV remodeling via increased peak pressures, cardiomyocyte loss, fibrosis, fiber reorientation, and altered mechanical properties in male Sprague-Dawley rats. Similarities were observed between aging-induced remodeling patterns and those of RV remodeling in pressure overload. These findings may help our understanding of age-related changes in the cardiovascular fitness and response to disease.

Background: Pulmonary hypertension (PH) is a life-threatening disease in dogs characterized by an increase in pulmonary arterial pressure (PAP) and/or pulmonary vascular resistance. Right ventricle adapts to its pressure overload through various right ventricular (RV) compensative mechanisms: adaptive and maladaptive remodeling. The former is characterized by concentric hypertrophy and increased compensatory myocardial contractility, whereas the latter is distinguished by eccentric hypertrophy associated with impaired myocardial function.Objectives: To evaluate the RV adaptation associated with the increase of PAP using two-dimensional speckle tracking echocardiography.Animals: Seven experimentally induced PH models.Methods: Dogs were anesthetized and then a pulmonary artery catheter was placed via the right jugular vein. Canine models of PH were induced by the repeated injection of microspheres through the catheter and monitored pulmonary artery pressure. Dogs were performed echocardiography and hemodynamic measurements in a conscious state when baseline and systolic PAP (sPAP) rose to 30, 40, 50 mmHg, and chronic phase. The chronic phase was defined that the sPAP was maintained at 50 mmHg or more for 4 weeks without injection of microspheres.Results: Pulmonary artery to aortic diameter ratio, RV area, end-diastolic RV wall thickness, and RV myocardial performance index were significantly increased in the chronic phase compared with that in the baseline. Tricuspid annular plane systolic excursion was significantly decreased in the chronic phase compared with that in the baseline. The RV longitudinal strain was significantly decreased in the sPAP30 phase, increased in the sPAP40 and sPAP50 phases, and decreased in the chronic phase.Conclusions: Changes in two-dimensional speckle tracking echocardiography-derived RV longitudinal strain might reflect the intrinsic RV myocardial contractility during the PH progression, which could not be detected by conventional echocardiographic parameters.

Background: Right ventricular (RV) free wall fibrosis is an important component of adverse remodeling with RV dysfunction in pulmonary hypertension (PH). However, no previous reports have compared cardiovascular magnetic resonance (CMR) findings and histological analysis for RV free wall fibrosis in PH. We aimed to assess the feasibility of CMR T1 mapping with extracellular volume fraction (ECV) for evaluating the progression of RV free wall fibrosis in PH, and compared imaging findings to histological collagen density through an animal study. Methods: Among 42 6-week-old Wistar male rats, 30 were classified according to disease duration (baseline before monocrotaline injection, and 2, 4, 6 and 8 weeks after injection) and 12 were used to control for aging (4 and 8 weeks after the baseline). We obtained pre and post-contrast T1 maps for native T1 and ECV of RV and left ventricular (LV) free wall for six animals in each disease-duration group. Collagen density of RV free wall was calculated with Masson's trichrome staining. The Kruskall-Wallis test was performed to compare the groups. Native T1 and ECV to collagen density were analyzed with Spearman's correlation. Results: The mean values of native T1, ECV and collagen density of the RV free wall at baseline were 1541 ± 33 ms, 17.2 ± 1.3%, and 4.7 ± 0.5%, respectively. The values of RV free wall did not differ according to aging (P = 0.244, 0.504 and 0.331, respectively). However, the values significantly increased according to disease duration (P < 0.001 for all). Significant correlations were observed between native T1 and collagen density (r = 0.770, P < 0.001), and between ECV and collagen density for the RV free wall (r = 0.815, P < 0.001) in PH. However, there was no significant difference in native T1 and ECV values for the LV free wall according to the disease duration from the baseline (P = 0.349 and 0.240, respectively). Conclusions: We observed significantly increased values for native T1 and ECV of the RV free wall without significant increase of the LV free wall according to the disease duration of PH, and findings were well correlated with histological collagen density. [ABSTRACT FROM AUTHOR]

There is limited evidence evaluating valve function and right heart remodeling after tricuspid valve replacement (TVR), as well as whether the choice of prosthesis has an impact on these outcomes. We reviewed 1043 consecutive adult patients who underwent first-time TVR; 33% had previous aortic and/or mitral valve operations. Severe tricuspid valve regurgitation (TR) was the indication for surgery in 94% patients. A mechanical valve was used in 149 (14%) patients and a bioprosthetic valve in 894 (86%). Concomitant major cardiac procedures were performed in 57% of patients. The median age of the cohort was 68.8 (range, 25-94) years, and 57% were female. Overall survival at 5 and 10 years was 50% and 31%, respectively. Adjusted survival and cumulative incidence of reoperation after TVR were similar in patients with bioprosthetic and mechanical valves. Overall, right ventricular (RV) function and dilation improved postoperatively with the estimated proportion of patients with moderate or greater RV systolic dysfunction/dilatation decreasing by around 20% at 3 years follow-up. After adjusting for preoperative degree of dysfunction/dilatation, valve type had no effect on late improvement in RV function and dilation. Bioprosthetic TVR was associated with greater rates of recurrence of moderate or greater TR over late follow-up. Overall, a slight decline in tricuspid valve gradients was observed over time. Mechanical and bioprosthetic valves provide comparable survival, incidence of reoperation, and recovery of RV systolic function and size after TVR. Bioprosthetic valves develop significant TR over time, and mechanical valves may have an advantage for younger patients and those needing anticoagulation. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive disease of pulmonary hypertension (PH) as a consequence obstructive of pulmonary arteries with thromboembolism. Augmented pulmonary vascular resistance and pulmonary artery pressure (PAP) can ultimately lead to the right ventricular dysfunction, which leads to adaptive and maladaptive changes. Right ventricle (RV) remodeling can cause clinical deterioration and RV failure. Aims and Objectives: We aimed to evaluate the RV functions with a new diagnostic modality 2-deoxy-2-(18F)-fluoro-D-glucose (FDG)-positron emission tomography (PET) in patients with CTEPH. Materials and Methods: We included 53 patients diagnosed with CTEPH who were planned to have pulmonary thromboendarterectomy (PEA) and did not have any contraindication for cardiac PET/computed tomography (CT). We performed transthoracic echo, cardiac PET/CT, 6-minute walk distance (6-MWT), and right heart catheterization 1 week before PEA surgery. Results: The patients divided into two groups according to RV/left ventricle (LV) FDG-PET uptake ratio, RV/LV ≤1, and RV/LV >1. Six-MWD was significantly higher in the RV/LV ≤1 group (P = 0.005). Pro-BNP was considerably higher in the RV/LV >1 group (P = 0.041). Conclusion: The present study aims to demonstrate the RV/LV FDG-PET uptake ratio could be used in the noninvasive diagnostic method in diagnosing, treatment strategy, and clinical follow-up in patients with CTEPH.

INTRODUCTION: Obstructive sleep apnea (OSA) is a common chronic pulmonary disease, characterized by repetitive collapse of the upper respiratory airways, leading to oxygen desaturation. This condition is recognized to be associated with cardiovascular disease. Several studies have shown the effects of OSA on both geometry and cardiac function, with conflicting results. We aimed to investigate the relationship between echocardiographic abnormalities and the severity of OSA. METHODS: this is a cross-sectional single center study including patients, without any cardiovascular or pulmonary comorbidities, with polygraphy proven OSA. All participant underwent a detailed transthoracic echocardiography (TTE). RESULTS: a total of 93 patients were included in the study, with 62.2% (n=56) females. According to the apnea hypopnea index (AHI), patients were divided into two groups: mild to moderate OSA (5 AHI 30/H) and severe OSA (AHI 30/H). There were no differences in baseline characteristics between the two groups. The assessment of echocardiographic parameters demonstrated that severe OSA have a higher left ventricular end-systolic (LVES) (47.6±7.2 VS 46.2±4.7), left ventricular end-diastolic (LVED) (31.3±6.2 VS 28.9±4.5) diameters and interventricular septum (IVS) thickness (12.7±2.4 VS11.7±2.5) diameters rather than mild to moderate OSA without a significant difference between the two groups. Furthermore, severe OSA patients had lower mean value of left ventricular ejection fraction (LVEF) and fractional shortening (FS) equal to 62.1±9.7 and 32.5±6.3 respectively. The difference between the two groups was not statistically significant. However, a significant association was shown between severity of OSA and left ventricular (LV) diastolic dysfunction, right ventricular internal diameter (RVID) and systolic pulmonary artery pressure (sPAP), with p=0.05, p=0.05 and p= 0.03 respectively. The RVID was also independently associated to the severity of the OSA (aOR 1.33, 95%CI:0.99-1.79; p=0.05). CONCLUSION: using bidimensional echocardiography showed a relationship between severe OSA and right ventricular parameters (diastolic dysfunction and RVID) and sPAP.

BackgroundRight ventricular (RV) function and failure are key determinants of morbidity and mortality in various cardiovascular diseases. Myocardial fibrosis is regarded as a contributing factor to heart failure, but its importance in RV failure has been challenged. This study aims to assess whether myocardial fibrosis drives the transition from compensated to decompensated volume load-induced RV dysfunction.MethodsWistar rats were subjected to aorto-caval shunt (ACS, n = 23) or sham (control, n = 15) surgery, and sacrificed after 1 month, 3 months, or 6 months. Echocardiography, RV pressure-volume analysis, assessment of gene expression and cardiac histology were performed.ResultsAt 6 months, 6/8 ACS-rats (75%) showed clinical signs of RV failure (pleural effusion, ascites and/or liver edema), whereas at 1 month and 3 months, no signs of RV failure had developed yet. Cardiac output has increased two- to threefold and biventricular dilatation occurred, while LV ejection fraction gradually decreased. At 1 month and 3 months, RV end-systolic elastance (Ees) remained unaltered, but at 6 months, RV Ees had decreased substantially. In the RV, no oxidative stress, inflammation, pro-fibrotic signaling (TGFβ1 and pSMAD2/3), or fibrosis were present at any time point.ConclusionsIn the ACS rat model, long-term volume load was initially well tolerated at 1 month and 3 months, but induced overt clinical signs of end-stage RV failure at 6 months. However, no myocardial fibrosis or increased pro-fibrotic signaling had developed. These findings indicate that myocardial fibrosis is not involved in the transition from compensated to decompensated RV dysfunction in this model.

Background: Studies on the management of functional tricuspid regurgitation (TR) during mitral valve operations have drawn inconsistent conclusions. This study was designed to compare the treatment strategy of concomitant tricuspid annuloplasty (TAP) against isolated mitral valve replacement (MVR) in rheumatic mitral valve disease patients, and to assess the effect of concomitant TAP on postoperative right ventricular (RV) remodeling and function. Methods: One hundred-seventy patients with rheumatic mitral valve disease receiving MVR were categorized into TAP group (n = 124) and non-TAP group (n = 46). Clinical and echocardiographic data were collected preoperatively and at 1-year follow-up. Three-dimensional echocardiographic indices of RV geometry and function were analyzed. Results: At baseline, concomitant TAP group had larger RV end-diastolic volume, more decreased RV ejection fraction and RV longitudinal strain than non-TAP group (all P < 0.001). At 1-year follow-up, TAP group had improved RV geometry and function. While adverse changes were observed in non-TAP group. In analysis of variance, the above indices demonstrated significant interaction with different treatment group (all P < 0.001). In multivariate regression analysis, independent of age and Maze procedure, concomitant TAP was associated with postoperative RV volume reduction (P < 0.001), improvement of RV ejection fraction (P < 0.001), and relieved postoperative functional TR severity (P = 0.025). Conclusions: Our results suggest that concomitant TAP could improve RV remodeling and function for rheumatic mitral valve disease patients, while those with mild preoperative functional TR who had isolated MVR might experience RV dilation and deterioration of RV function at follow-up. Concomitant surgery for functional TR could be considered for patients undergoing MVR with rheumatic mitral valve disease. [ABSTRACT FROM AUTHOR]

Background: Right ventricular (RV) function and failure are key determinants of morbidity and mortality in various cardiovascular diseases. Myocardial fibrosis is regarded as a contributing factor to heart failure, but its importance in RV failure has been challenged. This study aims to assess whether myocardial fibrosis drives the transition from compensated to decompensated volume load-induced RV dysfunction. Methods: Wistar rats were subjected to aorto-caval shunt (ACS, n = 23) or sham (control, n = 15) surgery, and sacrificed after 1 month, 3 months, or 6 months. Echocardiography, RV pressure-volume analysis, assessment of gene expression and cardiac histology were performed. Results: At 6 months, 6/8 ACS-rats (75%) showed clinical signs of RV failure (pleural effusion, ascites and/or liver edema), whereas at 1 month and 3 months, no signs of RV failure had developed yet. Cardiac output has increased two- to threefold and biventricular dilatation occurred, while LV ejection fraction gradually decreased. At 1 month and 3 months, RV end-systolic elastance (Ees) remained unaltered, but at 6 months, RV Ees had decreased substantially. In the RV, no oxidative stress, inflammation, pro-fibrotic signaling (TGFβ1 and pSMAD2/3), or fibrosis were present at any time point. Conclusions: In the ACS rat model, long-term volume load was initially well tolerated at 1 month and 3 months, but induced overt clinical signs of end-stage RV failure at 6 months. However, no myocardial fibrosis or increased pro-fibrotic signaling had developed. These findings indicate that myocardial fibrosis is not involved in the transition from compensated to decompensated RV dysfunction in this model. [ABSTRACT FROM AUTHOR]

Introduction: obstructive sleep apnea (OSA) is a common chronic pulmonary disease, characterized by repetitive collapse of the upper respiratory airways, leading to oxygen desaturation. This condition is recognized to be associated with cardiovascular disease. Several studies have shown the effects of OSA on both geometry and cardiac function, with conflicting results. We aimed to investigate the relationship between echocardiographic abnormalities and the severity of OSA. Methods: this is a cross-sectional single center study including patients, without any cardiovascular or pulmonary comorbidities, with polygraphy proven OSA. All participants underwent a detailed transthoracic echocardiography (TTE). Results: a total of 93 patients were included in the study, with 62.2% (n=56) females. According to the apnea hypopnea index (AHI), patients were divided into two groups: mild to moderate OSA (5≤ AHI< 30/H) and severe OSA (AHI≥ 30/H). There were no differences in baseline characteristics between the two groups. The assessment of echocardiographic parameters demonstrated that severe OSA have a higher left ventricular end-systolic (LVES) (47.6±7.2 VS 46.2±4.7), left ventricular end-diastolic (LVED) (31.3±6.2 VS 28.9±4.5) diameters and interventricular septum (IVS) thickness (12.7±2.4 VS11.7±2.5) diameters rather than mild to moderate OSA without a significant difference between the two groups. Furthermore, severe OSA patients had lower mean value of left ventricular ejection fraction (LVEF) and fractional shortening (FS) equal to 62.1±9.7 and 32.5±6.3 respectively. The difference between the two groups was not statistically significant. However, a significant association was shown between severity of OSA and left ventricular (LV) diastolic dysfunction, right ventricular internal diameter (RVID) and systolic pulmonary artery pressure (sPAP), with p=0.05, p=0.05 and p= 0.03 respectively. The RVID was also independently associated to the severity of the OSA (aOR 1.33, 95%CI: 0.99-1.79; p=0.05). Conclusion: using bidimensional echocardiography showed a relationship between severe OSA and right ventricular parameters (diastolic dysfunction and RVID) and sPAP. [ABSTRACT FROM AUTHOR]

Aims: Characterize the impact of residual tricuspid regurgitation (TR) on right ventricle (RV) remodeling and clinical outcomes after transcatheter tricuspid valve intervention., Methods: We performed a single-center retrospective analysis of transcatheter tricuspid valve repair (TTVr) or replacement (TTVR) patients. The primary outcomes were longitudinal tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), pulmonary artery systolic pressure (PASP), and RV dimensions (RVd). We used multivariable linear mixed models to evaluate association with replacement versus repair and degree of TR reduction with changes in these echo measures over time. Multivariable Cox regression was used to identify associations between changes in these echo measures and a composite clinical outcome of death, heart failure hospitalization, or re-do tricuspid valve intervention., Results: We included a total of 61 patients; mean age was 77.5 ± 11.7 and 62% were female. TTVR was performed in 25 (41%) and TTVr in 36 (59%). Initially, 72% (n = 44) had ≤ severe TR and 28% (n = 17) had massive or torrential TR. The median number of follow up echos was 2: time to 1st follow-up was 50 days (interquartile range [IQR]: 20, 91) and last follow-up was 147 (IQR: 90, 327). Median TR reduction was 1 (IQR: 0, 2) versus 4 (IQR: 3, 6) grades in TTVr versus TTVR (p < 0.0001). In linear mixed modeling, TTVR was associated with decline in TAPSE and PASP, and TR reduction was associated with decreased RVd. In multivariable Cox regression, greater RVd was associated with the clinical outcome (hazard ratio: 9.27, 95% confidence interval: 1.23-69.88, p = 0.03)., Conclusion: Greater TR reduction is achieved by TTVR versus TTVr, which is in turn associated with RV reverse remodeling. RV dimension in follow-up is associated with increased risk of a composite outcome of death, heart failure hospitalization, or re-do tricuspid valve intervention., (© 2023 Wiley Periodicals LLC.)

BackgroundPulmonary hypertension (PH) results in increased right ventricular (RV) afterload and ventricular remodeling. Sacubitril/valsartan (sac/val) is a dual acting drug, composed of the neprilysin inhibitor sacubitril and the angiotensin receptor blocker valsartan, that has shown promising outcomes in reducing the risk of death and hospitalization for chronic systolic left ventricular heart failure. In this study, we aimed to examine if angiotensin receptor‐neprilysin inhibition using sac/val attenuates RV remodeling in PH.Methods and ResultsRV pressure overload was induced in Sprague–Dawley rats via banding the main pulmonary artery. Three different cohorts of controls, placebo‐treated PH, and sac/val‐treated PH were studied in a 21‐day treatment window. Terminal invasive hemodynamic measurements, quantitative histological analysis, biaxial mechanical testing, and constitutive modeling were employed to conduct a multiscale analysis on the effects of sac/val on RV remodeling in PH. Sac/val treatment decreased RV maximum pressures (29% improvement, P=0.002), improved RV contractile (30%, P=0.012) and relaxation (29%, P=0.043) functions, reduced RV afterload (35% improvement, P=0.016), and prevented RV‐pulmonary artery uncoupling. Furthermore, sac/val attenuated RV hypertrophy (16% improvement, P=0.006) and prevented transmural reorientation of RV collagen and myofibers (P=0.011). The combined natriuresis and vasodilation resulting from sac/val led to improved RV biomechanical properties and prevented increased myofiber stiffness in PH (61% improvement, P=0.032).ConclusionsSac/val may prevent maladaptive RV remodeling in a pressure overload model via amelioration of RV pressure rise, hypertrophy, collagen, and myofiber reorientation as well as tissue stiffening both at the tissue and myofiber level.

Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure and right heart failure. Selective pulmonary vasodilators have improved the prognosis of PAH; however, they are not able to reverse pulmonary vascular remodeling. Therefore, a search for new treatment agents is required. H-1337 is an isoquinoline-sulfonamide compound that inhibits multiple serine/threonine kinases, including Rho-associated protein kinase (ROCK) and mammalian target of rapamycin (mTOR). Here, we investigated the effects of H-1337 on pulmonary hypertension and remodeling in the pulmonary vasculature and right ventricle in experimental PAH induced by SU5416 and hypoxia exposure. H-1337 and H-1337M1 exerted inhibitory effects on ROCK and Akt. H-1337 inhibited the phosphorylation of myosin light chain and mTOR and suppressed the proliferation of smooth muscle cells in vitro. H-1337 treatment also suppressed the phosphorylation of myosin light chain and mTOR in the pulmonary vasculature and decreased right ventricular systolic pressure and the extent of occlusive pulmonary vascular lesions. Furthermore, H-1337 suppressed aggravation of right ventricle hypertrophy. In conclusion, our data demonstrated that inhibition of ROCK and mTOR pathways with H-1337 suppressed the progression of pulmonary vascular remodeling, pulmonary hypertension, and right ventricular remodeling.

Background: The aim of the present retrospective study was to evaluate the influence of preoperative right ventricular (RV) and tricuspid valve (TV) remodeling on the fate of tricuspid annuloplasty (TA) and right ventricle.Methods: From May 2009 to December 2015, 423 patients who had undergone TA for functional tricuspid regurgitation (TR) were included in the study. Residual and recurrent TR were defined as moderate or more TR at discharge and follow-up, respectively. RV remodeling was defined as RV dysfunction and/or dilation.Results: Residual TR after TA was recorded in 54 patients (13%). Five-year freedom from TR recurrence was 81% ± 3% in patients without residual TR and 41 ± 8 in patients with residual TR (P < .001). In patients without residual TR, the following risk factors for recurrent TR and late RV remodeling were identified: preoperative systolic pulmonary artery pressure, preoperative RV remodeling, severe preoperative TR or less than severe TR but with TV apparatus remodeling, and etiology of mitral regurgitation. Cox analysis with time-dependent variables confirmed TR recurrence (hazard ratio [HR]: 3.1) and late RV remodeling (HR: 6.5) as risk factors for lower survival. No protective effect of either flexible band or rigid ring TA compared with DeVega procedure was found. Similarly, preoperative atrial fibrillation and pacemaker dependency, late failure of mitral valve surgery did not affect the fate of TR.Conclusions: Prophylactic TA should be encouraged among surgeons. TA at the time of left-sided valve surgery should take into consideration not only annular size, but also tethering severity and RV remodeling. [ABSTRACT FROM AUTHOR]

Before birth, the fetal right ventricle (RV) is the pump for the systemic circulation and is about as thick as the left ventricle (LV). After birth, the RV becomes the pump for the lower pressure pulmonary circulation, and the RV chamber elongates without change in its wall thickness. We hypothesize that the fetal RV may be a model of compensated RV hypertrophy, and understanding this process may aid in discovering therapeutic strategies for RV failure. We performed a literature review and identified pertinent articles from 1980 to present. The following topics were identified to be most pertinent in right ventricular involution: morphologic and histologic changes of the RV, cellular proliferation and terminal differentiation, the effect of stress on RV development, excitation contraction coupling and inotropic response change over time, and the amount of apoptosis through RV development. The RV changes on multiple levels after its transition from systemic to pulmonary circulation. Although published literature has variable results due partly from differences between animal models, the literature shows a clear need for more research in the field. [ABSTRACT FROM AUTHOR]

Both chronic obstructive pulmonary disease (COPD) and right ventricular (RV) dysfunction are common factors that have been associated with poor prognosis after aortic valve replacement (AVR). Since there is still uncertainty about the impact of COPD on RV function and dilatation in patients undergoing AVR, we sought to explore RV function and remodeling in the presence and absence of COPD as well as their prognostic implications. Patients who received surgical or transcatheter AVR due to severe AS were screened for COPD. Demographic and clinical data were collected at baseline while echocardiographic measurements were performed at baseline and 1 year after AVR. The study end-point was all-cause mortality. In total 275 patients were included, with 90 (33%) patients having COPD. At 1-year follow-up, mild worsening of tricuspid annular planar systolic excursion and RV dilatation were observed in patients without COPD, while there were significant improvements in RV longitudinal strain, RV wall thickness but dilatation of RV outflow tract distal dimension in the COPD group compared to the baseline. On multivariable analysis, the presence of COPD provided significant incremental prognostic value over RV dysfunction and remodeling. At 1-year after AVR, RV function and dimensions mildly deteriorated in non-COPD group whereas COPD group received significant benefit of AVR in terms of RV function and hypertrophy. COPD was independently associated with >2-fold all-cause mortality and had incremental prognostic value over RV dysfunction and remodeling. • COPD diagnosis based on pulmonary function test (PFT) is a reliable method for risk estimation before aortic valve replacement (AVR). • Both COPD and aortic stenosis cause RV dilatation and dysfunction, independently. • COPD patients can show a significant improvement after in AVR in terms of RV remodeling and function. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension of newborns (PAHN) constitutes a critical condition involving both severe cardiac remodeling and right ventricle dysfunction. One main cause of this condition is perinatal hypoxia and oxidative stress. Thus, it is a public health concern for populations living above 2500 m and in cases of intrauterine chronic hypoxia in lowlands. Still, pulmonary and cardiac impairments in PAHN lack effective treatments. Previously we have shown the beneficial effects of neonatal melatonin treatment on pulmonary circulation. However, the cardiac effects of this treatment are unknown. In this study, we assessed whether melatonin improves cardiac function and modulates right ventricle (RV) oxidative stress. Ten lambs were gestated, born, and raised at 3600 m. Lambs were divided in two groups. One received daily vehicle as control, and another received daily melatonin (1 mg·kg−1·d−1) for 21 days. Daily cardiovascular measurements were recorded and, at 29 days old, cardiac tissue was collected. Melatonin decreased pulmonary arterial pressure at the end of the experimental period. In addition, melatonin enhanced manganese superoxide dismutase and catalase (CAT) expression, while increasing CAT activity in RV. This was associated with a decrease in superoxide anion generation at the mitochondria and NADPH oxidases in RV. Finally, these effects were associated with a marked decrease of oxidative stress markers in RV. These findings support the cardioprotective effects of an oral administration of melatonin in newborns that suffer from developmental chronic hypoxia.

Hypoxia inducible factor-1(HIF-1), a heterodimeric transcription factor, is composed of two subunits (HIF-1α and HIF-1β). It is considered as an important transcription factor for regulating oxygen changes in hypoxic environment, which can regulate the expression of various hypoxia-related target genes and play a role in acute and chronic hypoxia pulmonary vascular reactions. In this paper, the function and mechanism of HIF-1a expression and regulation in hypoxic pulmonary hypertension (HPH) were reviewed, and current candidate schemes for treating pulmonary hypertension by using HIF-1a as the target were introduced, so as to provide reference for studying the pathogenesis of HPH and screening effective treatment methods., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: Pulmonary arterial hypertension (PAH) means high blood pressure in the lungs. We aimed to observe the right ventricular size, wall thickness and characteristic functional changes and their associations with PAH in an established model of beagle dogs, and to explore convenient, reliable and sensitive ultrasound indicators for assessing right ventricular remodeling., Methods: Twenty healthy beagle dogs (8-10 kg) were randomly divided into control group (N-dimethylformamide, n  = 10) and dehydromonocrotaline (DHMCT) group (DHMCT, n  = 10). N-dimethylformamide or DHMCT was injected through a catheter into the right atrium, and then right heart catheterization, routine echocardiography and two-dimensional speckle tracking imaging (2D-STI) were performed before modeling (0 weeks) and 8, 14 weeks after modeling. Hemodynamic parameters and right ventricular function-related ultrasound data were acquired. At the end of the experiment, the animals were killed and the lung tissues were taken for HE staining. Left and right ventricular walls were separated and weighed respectively, and right ventricular hypertrophy index (RVHI) was measured. The associations of the routine ultrasound data and 2D-STI data at each time point with hemodynamic parameters and RVHI were analyzed., Results: At 0, 8 and 14 weeks, gradual decreases in the right ventricular global longitudinal strain (RVLS) were found in DHMCT group. RVH occurred in DHMCT group, and DHMCT group had a significantly higher RVHI than that of control group (49.83 ± 4.83% vs. 39.80 ± 1.40%, P  < .001) and larger pulmonary artery media thickness. RVLS had significant positive correlations with RVSP ( r  = 0.74, P  < .001), mRVP ( r  = 0.72, P  < .001), PASP ( r  = 0.75, P  < .001), mPAP ( r  = 0.72, P  < .001) and PVR ( r  = 0.68, P  < .001). There was a significant positive correlation between RVLS and RVHI ( r  = 0.74, P  < .001)., Conclusion: The right ventricular function in PAH can be effectively assessed by echocardiography, and RVLS measured by 2D-STI sensitively reflects right ventricular remodeling following PAH.

Background: We sought to identify subgroups of patients at a higher probability of tricuspid annuloplasty (TAP) failure early after surgery.Methods: From May 2009 to December 2015, 688 patients undergoing TAP for functional tricuspid regurgitation (FTR) at a single institution were included in the study. In all patients, a complete transthoracic echocardiographic evaluation of right ventricle (RV) and tricuspid valve (TV) apparatus was collected.Results: Twenty-six patients (3.8%) died within the first 30 days of surgery. Residual TR after TAP was recorded in 85 (12.4%), moderate in 80 (11.7%) and severe in 5 (0.7%). Preoperative TV apparatus remodeling was associated with residual TR; in particular, the following cutoffs were identified: TV coaptation depth ≥6.5 mm, tenting area ≥0.85 cm2 , and tricuspid annulus ≥35 mm. The entire cohort was stratified in three subsets: patients having preoperative mild/moderate TR without preoperative TV apparatus and/or RV remodeling (n = 178); patients having mild/moderate TR with TV apparatus and/or RV remodeling (n = 317); patients with severe TR regardless of TV apparatus and/or RV remodeling (n = 193). Residual TR was 2.8%, 10.4%, and 24.3%, respectively (P < 0.001). At multivariable analysis, patients showing preoperative mild/moderate TR with TV apparatus and/or RV remodeling as well as patients with severe TR were at significantly higher risk for early failure. No difference was found regarding the type of TV repair performed.Conclusions: Prophylactic TAP should be encouraged among surgeons even earlier than guidelines recommend, and decision-making for the treatment of low-grade FTR at the time of left-sided valve surgery should take into consideration not only annular size but also tethering severity and RV dilatation. [ABSTRACT FROM AUTHOR]

Abstract Aim Pulmonary hypertension due to left heart failure (PH-LHF) is the most common cause of pulmonary hypertension. However, therapies for PH-LHF are lacking. Therefore, we investigated the effects and potential mechanism of dehydroepiandrosterone (DHEA) treatment in an experimental model of PH-LHF. Main method PH-LHF was induced in rats via ascending aortic banding. The rats then received daily DHEA from Day 1 to Day 63 for the prevention protocol or from Day 49 to Day 63 for the reversal protocol. Other ascending aortic banding rats were left untreated to allow development of PH and right ventricular (RV) failure. Sham ascending aortic banding rats served as controls. Key finding Significant increases in mean pulmonary arterial pressure (mPAP) and right ventricular end-diastolic diameter (RVEDD) were observed in the PH-LHF group. Therapy with DHEA prevented LHF-induced PH and RV failure by preserving mPAP and preventing RV hypertrophy and pulmonary artery remodeling. In preexisting severe PH, DHEA attenuated most lung and RV abnormalities. The beneficial effects of DHEA in PH-LHF seem to result from depression of the STAT3 signaling pathway in the lung. Significant DHEA not only prevents the development of PH-LHF and RV failure but also rescues severe preexisting PH-LHF. [ABSTRACT FROM AUTHOR]