RV Remodeling Research Articles

Edge-to-edge repair for tricuspid valve regurgitation: 1-year follow up and clinical implications from the TR- Interventional Study (TRIS)

Abstract Background Tricuspid regurgitation (TR) affects 7% of the population, contributing significantly to heart failure-related hospitalizations. Traditional treatments have several limitations, prompting the exploration of innovative interventions. Purpose The present study aims to investigate the efficacy of tricuspid valve transcatheter edge-to-edge repair (T-TEER) in real-world patients with severe and symptomatic TR deemed at high surgical risk. Primary objectives focus on assessing T-TEER-induced TR reduction and reverse structural remodeling of the RV. Secondary objectives include assessment of functional status, quality of life, and residual regurgitation during the 12-month follow-up period. Methods The TR-Interventional study (TRIS) is a prospective, single-arm study. From January 2021 to December 2023, we enrolled 44 symptomatic patients with at least severe TR referred for TEER. Outcomes included safety and effectiveness along with assessment of clinical status. Results The study cohort had a mean age of 78.3±7 years, with 77.3% women and a mean TRISCORE of 5.1±1.9. Seventeen patients (38.6%) had massive, 7 (15.9%) had torrential, and 20 (45.5%) patients had severe TR. Etiologies included functional (40.9%), degenerative (13.64%), lead-induced (15.9%), and mixed (29.54%) origin. The primary efficacy endpoint, which assesses the successful implantation and performance of the device at the 30-day mark, was attained in 82.9% of patients. The secondary efficacy endpoint, assessing the stability of TR reduction at the 12-month, was achieved in 82,3% of patients. Post-procedural TR reduction of at least 2 degrees was achieved in 84% of patients. Echocardiographic assessments indicate ongoing beneficial remodeling over the one-year follow-up (Figure 1). Effects on RV remodeling also became apparent at the one-year follow-up, including reductions in the RV end-diastolic basal (p<0.01) and medium (p= 0.04) diameters of the TA septal-lateral diameter (p< 0.01). Significant reduction in vena contracta width (9 mm to 3 mm; p=<0.01), regurgitant volume (58 ml to 30 ml; p<0.01), and effective regurgitant orifice area (EROA) (0.6 cm2 to 0.3 cm2; p<0.01), occurred between baseline and one-year follow-up (Figure 2). The NYHA Functional Class and KCCQ scores were improved from 30 days to 1 year (Figure 2). Conclusion TRIS suggests that T-TEER is a durable, effective, and safe therapeutic option for high-risk patients with severe TR. The enduring nature of TR reduction at one year correlates with sustained clinical benefits and reverse structural remodeling of the right ventricle.TR reductionNYHA and functional status

The effects of percutaneous branch pulmonary artery interventions in biventricular congenital heart disease: study protocol for a randomized controlled Dutch multicenter interventional trial

BackgroundBranch pulmonary artery (PA) stenosis is one of the most common indications for percutaneous interventions in patients with transposition of the great arteries (TGA), tetralogy of Fallot (ToF), and truncus arteriosus (TA). However, the effects of percutaneous branch PA interventions on exercise capacity remains largely unknown. In addition, there is no consensus about the optimal timing of the intervention for asymptomatic patients according to international guidelines. This trial aims to identify the effects of percutaneous interventions for branch PA stenosis on exercise capacity in patients with TGA, ToF, and TA. In addition, it aims to assess the effects on RV function and to define early markers for RV adaptation and RV dysfunction to improve timing of these interventions.MethodsThis is a randomized multicenter interventional trial. TGA, ToF, and TA patients ≥ 8 years with a class IIa indication for percutaneous branch PA intervention according to international guidelines are eligible to participate. Patients will be randomized into the intervention group or the control group (conservative management for 6 months). All patients will undergo transthoracic echocardiography, cardiac magnetic resonance (CMR) imaging, and cardiopulmonary exercise testing at baseline, 6 months, and 2–4 years follow-up. Quality of life (QoL) questionnaires will be obtained at baseline, 2 weeks post intervention or a similar range for the control group, and 6 months follow-up. The primary outcome is exercise capacity expressed as maximum oxygen uptake (peak VO2 as percentage of predicted). A total of 56 patients (intervention group n = 28, control group n = 28) is required to demonstrate a 14% increase in maximum oxygen uptake (peak VO2 as percentage of predicted) in the interventional group compared to the control group (power 80%, overall type 1 error controlled at 5%). Secondary outcomes include various parameters for RV systolic function, RV functionality, RV remodeling, procedural success, complications, lung perfusion, and QoL.DiscussionThis trial will investigate the effects of percutaneous branch PA interventions on exercise capacity in patients with TGA, ToF, and TA and will identify early markers for RV adaptation and RV dysfunction to improve timing of the interventions.Trial registrationClinicalTrials.gov NCT05809310. Registered on March 15, 2023.

Right ventricular phenotyping in incident patients with idiopathic pulmonary arterial hypertension

BackgroundRight ventricular (RV) imaging has not a definite role in risk stratification of pulmonary arterial hypertension (PAH) patients. We tested the hypothesis that echocardiography-derived phenotypes, depicting different degrees of RV remodeling and dysfunction, may provide additional prognostic information to current risk stratification tools. MethodsConsecutive incident PAH patients aged ≥ 18 years, diagnosed between January 2005 and December 2021, underwent clinical assessment, right heart catheterization, standard echocardiography. Simple echocardiographic variables were combined in order to define a priori four phenotypes representing different degrees of RV dilatation and RV-pulmonary arterial (PA) coupling: Phenotype 1 with mildy dilated right ventricle and preserved RV-PA coupling (n=152 patients); phenotype 2 with mildly dilated right ventricle and poor RV-PA coupling (n=143 patients); phenotype 3 with severely dilated right ventricle and preserved RV-PA coupling (n=201 patients); phenotype 4 with severely dilated right ventricle and poor RV-PA coupling, with or without severe tricuspid regurgitation (n=519 patients). Risk stratification was based on on the ESC/ERS 3-strata model and REVEAL 2.0 score. ResultsThese phenotypes were present in all risk groups. Notably, regardless of the ESC/ERS risk stratum assigned to the patient, phenotype 4 was associated with a 2-fold increase of the odds of death (HR 2.1, 95% C.I. 1.6-2.8, p<0.001), while phenotype 1 was associated with a 71% reduction in the odds of dying (HR 0.29, 95% C.I. 0.18-0.47, p<0.001). ConclusionsEchocardiography-derived phenotypes describing RV remodeling and dysfunction may provide prognostic information which is independent of and additional to the clinically defined risk in incident PAH patients.

Performance of Transcatheter Direct Annuloplasty in Patients With Atrial and Nonatrial Functional Tricuspid Regurgitation

BackgroundA novel echocardiography-based definition of atrial functional tricuspid regurgitation (A-FTR) has shown superior outcomes in patients undergoing conservative treatment or tricuspid valve transcatheter edge-to-edge repair. Its prognostic significance for transcatheter tricuspid valve annuloplasty (TTVA) outcomes is unknown. ObjectivesThis study sought to investigate prognostic, clinical, and technical implications of A-FTR phenotype in patients undergoing TTVA. MethodsThis multicenter study investigated clinical and echocardiographic outcomes up to 1 year in 165 consecutive patients who underwent TTVA for A-FTR (characterized by the absence of tricuspid valve tenting, midventricular right ventricular [RV] dilatation, and impaired left ventricular ejection fraction) and nonatrial functional tricuspid regurgitation (NA-FTR). ResultsA total of 62 A-FTR and 103 NA-FTR patients were identified, with the latter exhibiting more pronounced RV remodeling. Compared to baseline, the tricuspid regurgitation (TR) grade at discharge was significantly reduced (P < 0.001 for both subtypes), and TR ≤II was achieved more frequently in A-FTR (85.2% vs 60.8%; P = 0.001). Baseline TR grade and A-FTR phenotype were independently associated with TR ≤II at discharge and 30 days. In multivariate analyses, A-FTR phenotype was a strong predictor (OR: 5.8; 95% CI: 2.1-16.1; P < 0.001) of TR ≤II at 30 days. At 1 year, functional class had significantly improved compared to baseline (both P < 0.001). One-year mortality was lower in A-FTR (6.5% vs 23.8%; P = 0.011) without significant differences in heart failure hospitalizations (13.3% vs 22.7%; P = 0.188). ConclusionsDirect TTVA effectively reduces TR in both A-FTR, which is a strong and independent predictor of achieving TR ≤II, and NA-FTR. Even though NA-FTR showed more RV remodeling at baseline, both phenotypes experienced similar symptomatic improvement, emphasizing the benefit of TTVA even in advanced disease stages. Additionally, phenotyping was of prognostic relevance in patients undergoing TTVA.

Improvement in atrial functional and ventricular functional tricuspid regurgitation following catheter ablation or cardioversion of atrial fibrillation

Abstract Background The majority of cases of significant tricuspid regurgitation (TR) are secondary to tricuspid annular dilation and leaflet tethering in the context of RV remodeling due to pressure or volume overload, as seen in patients with pulmonary hypertension (primary or secondary to left-sided heart disease) or dilated cardiomyopathies. Secondary TR induced by tricuspid valve annular dilatation secondary to right atrial dilatation is referred to as atrial functional TR, while secondary TR caused by RV remodeling is referred to as ventricular functional TR. In current guidelines, GDMT (Guideline-Directed Medical Therapy) is effective for secondary TR attributable to HF with reduced LVEF. Normal sinus rhythm should be restored for secondary TR caused by AF-related annular dilatation. In patients with ventricular functional TR, however, AF may also accompany the clinical condition. It is unknown whether restoring sinus rhythm will reduce tricuspid regurgitation in these patients. Purpose The objective of this study was to investigate the degree of tricuspid regurgitation change in patients with atrial and ventricular functional tricuspid regurgitation after sinus rhythm restoration. Methods A retrospective cohort study of patients undergoing AF ablation and cardioversion at a single center between 2019 and 2023 was performed. Patients with at least grade 1 TR on echocardiography and a baseline echocardiogram and a follow-up echocardiogram after ablation were included. A-FTR and V-FTR were defined according to the latest ACC/AHA guidelines. According to the latest guidelines, patients with mild to severe FTR were classified as A-FTR if they had atrial fibrillation, left ventricular ejection fraction &amp;gt;60%, pulmonary artery systolic pressure (PASP) &amp;lt;50 mm Hg, no left-sided valve disease, and normal-appearing tricuspid leaflets. FTR patients who did not meet at least one of these three criteria were defined as ventricular FTR (V-FTR). Results A total of 88 patients were enrolled. The prevalence of A-FTR in our cohort was 62% (53 patients), and 38% of the patients were in the V-FTR group. There was no significant difference between the A-FTR and V-FTR groups regarding age, gender, and NYHA class. 21 of the patients underwent DCCV, and 67 underwent catheter ablation. The prevalence of severe FTR was similar (%17 in A-FTR vs. %8,6 in V-FTR, p= 0.205). There was no difference in preintervention TR grade between the two groups. TR severity improved significantly from baseline to follow-up in both V-FTR and A-FTR patients. These outcomes were observed in patients who underwent both DCCV and catheter ablation. Conclusion The degree of tricuspid regurgitation is reduced with sinus rhythm restoration in patients with both ventricular functional and atrial functional TR.Changes in TR severity with interventionGraph of changes in severity of TR

Circulating Biomarkers in Pulmonary Arterial Hypertension: An Update.

Pulmonary arterial hypertension (PAH) is a rare subtype of group 1 pulmonary hypertension (PH) diseases, characterized by high pulmonary artery pressure leading to right ventricular dysfunction and potential life-threatening consequences. PAH involves complex mechanisms: vasoconstriction, vascular remodeling, endothelial dysfunction, inflammation, oxidative stress, fibrosis, RV remodeling, cellular hypoxia, metabolic imbalance, and thrombosis. These mechanisms are mediated by several pathways, involving molecules like nitric oxide and prostacyclin. PAH diagnosis requires clinical evaluation and right heart catheterization, confirming a value of mPAP ≥ 20 mmHg at rest and often elevated pulmonary vascular resistance (PVR). Even if an early and accurate diagnosis is crucial, PAH still lacks effective biomarkers to assist in its diagnosis and prognosis. Biomarkers could contribute to arousing clinical suspicion and serve for prognosis prediction, risk stratification, and dynamic monitoring in patients with PAH. The aim of the present review is to report the main novelties on new possible biomarkers for the diagnosis, prognosis, and treatment monitoring of PAH.

Identification of an optimal method for echocardiographic right ventricular mass estimation in a swine model of pulmonary hypertension

Abstract Background Right ventricular (RV) mass and Fulton Index (FI) - the ratio of right to left ventricular mass - are useful markers of RV remodeling and predictors of mortality in pulmonary hypertension (PH). Cardiac magnetic resonance imaging provides an accurate estimation of RV mass but cost, availability and patient contraindications limit broad application. While echocardiography is universally available and offers feasible longitudinal assessments, current guidelines lack a standardized method for RV mass determination. Purpose We compared the performance of four previously described echocardiographic models of RV mass to estimate actual RV weight and FI measured post-mortem in a swine model of PH. Methods Echocardiography was performed in a Yorkshire pig model of post-capillary PH induced by pulmonary vein banding and healthy animals using a Philips iE-33 ultrasound system (n=70). RV mass was measured using the following models: trapezoid method (1), exact radius method (2), longitudinal plane method (3), and an algorithm (4) proposed by Kochav's group. Figure 1 depicts pertinent echocardiographic views and parameters. A two-dimensional area-length method was applied to estimate left ventricular mass and FI was calculated. On the day of echocardiography, pigs were euthanized, hearts were explanted, and ventricular weights were recorded. Pearson’s correlation, linear regression and Bland-Altman analysis were employed to evaluate different methods compared to recorded weights and Fulton Index. Results PH animals presented with significant RV remodeling and higher RV weights (42.4g, range 18.4-93.6g) compared to control pigs (30.5g, range 11.1-46.0g), allowing for examination of echocardiographic methods across a wide span of RV weights. FI ranged from 0.29 to 3.60 with a mean of 0.70. All methods demonstrated a strong linear relationship with post-mortem RV weight (r(1) = 0.88, r(2) = 0.88, r(3) = 0.84 r(4) = 0.82, p&amp;lt;0.0001). Bland-Altmann analysis revealed good agreement with recorded RV mass for trapezoid, exact radius and longitudinal plane method (bias(1) = 4.5±7.5g, bias(2) = -5.9±6.6g, bias(3) = -2.7±8.4g) while Kochav’s algorithm tended to underestimate RV weights (bias(4) = -18.5±8.7g). Figure 2 illustrates the performance of exact radius and longitudinal plane methods. Measured left ventricular mass correlated strongly with post-mortem left ventricular weight and reached good agreement (r = 0.91, p&amp;lt;0.0001; bias = -4.0±9.8g). FI was best approximated by exact radius (bias = -0.04±0.12) and longitudinal plane (bias = 0.01±0.18) methods. The trapezoid model tended to overestimate FI (bias = 0.10±0.11) and Kochav’s algorithm underestimated (bias = -0.23±0.12). Conclusion RV mass and FI can be successfully approximated using echocardiography in a clinically relevant porcine PH model. Longitudinal plane and exact radius methods performed best and can be suggested for evaluating RV mass in clinical PH patients.Figure 1Figure 2

Abstract 18286: Histone Acetyltransferase P300/CBP in Pulmonary Arterial Hypertension and Associated Right Ventricular Failure

INTRODUCTION Pulmonary arterial hypertension (PAH) is defined by increased pulmonary artery (PA) pressure and vascular remodeling, partly due to excessive proliferation and survival of PA smooth muscle cells (PASMCs). Initially, RV hypertrophy allows adaptation to increased resistance, but as the disease progresses, maladaptive remodeling takes place, leading to RV failure and death. Current therapies aim to promote vasodilatation, but none of them directly targets pathological lungs or RV remodeling. The histone acetyltransferases P300/CBP have been identified as central players driving gene expression in various cellular processes such as proliferation/apoptosis and hypertrophy/fibrosis, all of which are critical features of pathological lung and RV remodeling in PAH. Given their role in controlling gene transcription programs, we hypothesized that P300/CBP contributes to maladaptive remodeling. METHODS &amp; RESULTS We show by western blot (WB) and immunofluorescence (IF) increased P300 expression in isolated PASMCs and distal PAs from PAH patients compared to controls (p&lt;0.01) as well as in monocrotaline (MCT) and sugen-hypoxia rat models (p&lt;0.05). Similar results are observed in remodeled RV from PAH patients, MCT- and pulmonary artery banding-subjected rats (WB). In vitro, P300/CBP inhibition (CCS-1477 or siRNA) reduces H3K27 acetylation (WB, p&lt;0.05) in PAH-PASMCs and RV fibroblasts (RVFbs). This effect is accompanied by a decrease in PAH-PASMC proliferation and resistance to apoptosis [WB (PCNA, PLK1, Survivin), IF (Ki67, AnexinV), p&lt;0.01]. Similarly, P300/CBP inhibition reduces proliferation (WB, PCNA, Survivin) and activation/extracellular matrix production (WB, pSMAD2/3, aSMA, Fn, Col1, MMP2) in RVFbs. In addition, P300/CBP inhibition prevents phenylephrine-induced hypertrophy in H9C2 cells and adult rat cardiomyocytes (IF, p&lt;0.05). In vivo, administration of CCS-1477 reduces pulmonary vascular remodeling (Elastica Van Gieson, p&lt;0.05), improves pulmonary hemodynamics (p&lt;0.01) and attenuates RV fibrosis (Masson’s Trichrome, p&lt;0.05) in MCT rats with established PAH. Conclusion: We provide evidence that targeting P300/CBP may represent a promising avenue to tackle both lung and RV maladaptive remodeling in PAH.

Multi-omic and multispecies analysis of right ventricular dysfunction

Right ventricular failure (RVF) is a leading cause of morbidity and mortality in multiple cardiovascular diseases, but there are no treatments for RVF as therapeutic targets are not clearly defined. Contemporary transcriptomic/proteomic evaluations of RVF are predominately conducted in small animal studies, and data from large animal models are sparse. Moreover, a comparison of the molecular mediators of RVF across species is lacking. Transcriptomics and proteomics analyses defined the pathways associated with cardiac magnetic resonance imaging (MRI)-derived values of RV hypertrophy, dilation, and dysfunction in control and pulmonary artery banded (PAB) pigs. Publicly available data from rat monocrotaline-induced RVF and pulmonary arterial hypertension patients with preserved or impaired RV function were used to compare molecular responses across species. PAB pigs displayed significant right ventricle/ventricular (RV) hypertrophy, dilation, and dysfunction as quantified by cardiac magnetic resonance imaging. Transcriptomic and proteomic analyses identified pathways associated with RV dysfunction and remodeling in PAB pigs. Surprisingly, disruptions in fatty acid oxidation (FAO) and electron transport chain (ETC) proteins were different across the 3species. FAO and ETC proteins and transcripts were mostly downregulated in ratsbut were predominately upregulated in PAB pigs, which more closely matched the human response. All species exhibited similar dysregulation of the dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy pathways. The porcine metabolic molecular signature was more similar to human RVF than rodents. These data suggest there may be divergent molecular responses of RVF across species, and pigs may more accurately recapitulate metabolic aspects of human RVF.

Abstract P2143: New Rock Inhibitor Improves Pulmonary Vascular Resistance And Right Ventricle Function In Animal Model Of Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is characterised by increased pulmonary arterial pressure and vascular thickening, which causes RV dysfunction and failure. Current therapies lack efficacy for preventing disease progression and lead to poor survival rate in patients. Rho-activated protein kinases (ROCK) play a key role in smooth muscle contraction and proliferation and cardiomyocyte hypertrophy and survival, which indicate the potential of ROCK inhibitors to treat PAH. This work aims to assess the efficacy of a novel ROCK inhibitor, named LASSBio-2065, on cardiac and vascular function in monocrotaline (MCT)-induced PAH. Intraperitoneal injection of 60 mg/kg MCT induced PAH in Wistar rats, which protocol was approved by the Animal Care and Use Committee at Universidade Federal do Rio de Janeiro. After 2 wks, echocardiography confirmed the PAH and rats were randomly divided in groups and treated with either vehicle or LASSBio-2065 (60 μmol/kg/day, i.p.) for 14 days. At the end of treatment, hemodynamic parameters were evaluated using echocardiography and RV catheterization. Tissues were collected for histologic and morphometric analysis. Data expressed as mean ± SEM was analysed using One-way ANOVA followed by Dunnett post-test. LASSBio-2065 improves pulmonary vascular resistance and RV afterload because the ratio of pulmonary acceleration time-to-total ejection time reduced from 26.7 ± 2.0 to 21.7 ± 1.6 (p&lt; 0.05) and RV output from 64.2 ± 6.1 to 39.1 ± 8.0 (p&lt;0.05). Vascular and cardiac remodelling were prevented by LASSBio-2065, since medial wall thickness of distal pulmonary arterioles reduced and short axis RV-to-LV internal area increased from 85.8 ± 11.4 to 115.2 ± 17.8 (p&lt;0.05). The new ROCK inhibitor also improved the RV diastolic function, restoring both RV end-diastolic pressures increasing from 5.3 ± 0.8 to 11.1 ± 1.9 mmHg (p&lt;0.05) and Tau from 16.9 ± 2.2 to 27.1 ± 2.8 (p&lt;0.05). In conclusion, LASSBio-2065 significantly improved RV function in MCT-induced PAH. In conclusion, the new ROCK inhibitor represents a potential alternative for management of PAH-associated RV dysfunction and remodelling.

Spatial and temporal resolution of metabolic dysregulation in the Sugen hypoxia model of pulmonary hypertension

AbstractAlthough PAH is partially attributed to disordered metabolism, previous human studies have mostly examined circulating metabolites at a single time point, potentially overlooking crucial disease biology. Current knowledge gaps include an understanding of temporal changes that occur within and across relevant tissues, and whether observed metabolic changes might contribute to disease pathobiology. We utilized targeted tissue metabolomics in the Sugen hypoxia (SuHx) rodent model to investigate tissue‐specific metabolic relationships with pulmonary hypertensive features over time using regression modeling and time‐series analysis. Our hypotheses were that some metabolic changes would precede phenotypic changes, and that examining metabolic interactions across heart, lung, and liver tissues would yield insight into interconnected metabolic mechanisms. To support the relevance of our findings, we sought to establish links between SuHx tissue metabolomics and human PAH ‐omics data using bioinformatic predictions. Metabolic differences between and within tissue types were evident by Day 7 postinduction, demonstrating distinct tissue‐specific metabolism in experimental pulmonary hypertension. Various metabolites demonstrated significant tissue‐specific associations with hemodynamics and RV remodeling. Individual metabolite profiles were dynamic, and some metabolic shifts temporally preceded the emergence of overt pulmonary hypertension and RV remodeling. Metabolic interactions were observed such that abundance of several liver metabolites modulated lung and RV metabolite‐phenotype relationships. Taken all together, regression analyses, pathway analyses and time‐series analyses implicated aspartate and glutamate signaling and transport, glycine homeostasis, lung nucleotide abundance, and oxidative stress as relevant to early PAH pathobiology. These findings offer valuable insights into potential targets for early intervention in PAH.

How should right ventricle remodeling be assessed in women and men with chronic mitral regurgitation?

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Haukeland University Hospital Introduction Right ventricular (RV) dysfunction has a negative impact in patients with mitral regurgitation (MR), yet its assessment by two-dimensional (2D) echocardiography remains challenging. It is unclear which echocardiographic parameter best reflects RV remodeling in chronic MR. Purpose To assess 2D and three-dimensional (3D) measures of RV size and function in relation to MR severity. Methods Patients in the 3D-PRIME (3D Echocardiography and Cardiovascular Prognosis in Mitral Regurgitation) study with moderate or severe MR by combined transthoracic/transesophageal assessment and no other severe valve disease were examined at our heart valve clinic between 2020–2022. RV remodeling was assessed in 2D by the basal diameter, tissue Doppler peak systolic velocity at the lateral tricuspid ring (RV s´), tricuspid annular plane systolic excursion (TAPSE), and RV free wall longitudinal strain (RV FWS); and in 3D by end-diastolic volume (3D RVEDV), end-systolic volume (3D RVESV), ejection fraction (3D RVEF) and fractional area change (3D RVFAC). Results 100 patients with moderate or severe MR (54 with degenerative MR; 26 with atrial functional MR; 20 with ventricular functional MR) were included. Women (n=38) had smaller MR regurgitation volumes and RV size, similar TAPSE and RV s´, but higher 3D RVEF, 3D RVFAC and RV strain normalized for 3D RVEDV (all p &amp;lt;0.05). More severe RV remodeling with larger volumes, and lower 3D RVFAC (all p &amp;lt;0.05), and 3D RVEF (p = 0.05) was detected in severe MR by 3D, but not by 2D RV measures (Figure). In ROC analyses, 3D RVESV was strongest associated with severe MR (area under curve 0.68, p &amp;lt;0.01, Figure). In linear regression analysis, increasing 3D RVESV was associated with higher body mass index, larger MR regurgitation volume, male sex, and larger 3D left atrial volumes (R2 0.48, p &amp;lt;0.001). Conclusion RV remodeling in severe MR is detected by 3D, but not by routine 2D echocardiography. The 3D RV end-systolic size best reflects MR severity.

Mechanical adaptation of the right ventricle to increased volume overload associated with secondary tricuspid regurgitation

Abstract Funding Acknowledgements Type of funding sources: None. Background Right ventricular (RV) function is strongly associated with the prognosis of patients with secondary tricuspid regurgitation (STR). However, the mechanical adaptations (contraction pattern) of the RV to volume overload associated with STR remain to be clarified. Purpose To investigate the changes in RV contraction pattern associated with the increase in severity of STR and to analyse whether the assessment of each RV motion component of RV ejection fraction (RVEF) (longitudinal, radial, and anteroposterior) adds prognostic value in patients with STR. Methods Consecutive patients with STR who underwent clinically indicated transthoracic echocardiography were enrolled in a multi-center prospective observational study. The primary outcome was defined as heart failure hospitalization or cardiac death. 3-dimensional echocardiography studies were performed at baseline and the ReVISION software package (Argus Cognitive, Inc, Lebanon, NH) was used to quantify the contribution of the longitudinal, radial, and anteroposterior motion components to total RVEF (Figure). Results We enrolled 172 patients (43% men, age: 75±15 years), followed for a median of 9 months. The patients were divided in two groups by STR severity (non-severe n=125, severe n=47). The characteristics of patients with massive/torrential STR (n=12) vs. "only" severe STR (n=35) were also assessed. RV end-diastolic volume index (r=0.33, p&amp;lt;0.001) and the longitudinal component of RVEF demonstrated significant correlation with STR severity (r=-0.22, p&amp;lt;0.01), while total RVEF did not (r=0.14; p = NS). The anteroposterior component of RVEF was the only parameter showing relatively strong correlation with left ventricular ejection fraction (r=0.39; p&amp;lt;0.001). RVEF was comparable between non-severe and severe patients (49±10 vs. 49±11%, p = NS). In patients with severe STR, the radial and also anteroposterior component of RVEF were comparable to non-severe STR patients, while the longitudinal component was significantly lower in severe STR (19±6 vs.17±7%, p&amp;lt;0.05; shown on Figure). Notably, in patients with massive/torrential STR, the radial contribution markedly decreased (27±8 vs. 20±9%, p&amp;lt;0.05), with consequently reduced global RVEF (52±9 vs. 41±12%, p&amp;lt;0.01) (Figure). In a multivariable Cox regression, using parameters proved to be significant in the univariable analysis, longitudinal component of total RVEF was a significant and independent predictor of outcome (hazard ratio, 0.947 [CI, 0.903–0.992], P= 0.022). Conclusions Patients with severe STR demonstrate significant morphological and functional RV remodeling with chamber enlargement and maintained RVEF, but a significant decrease in the longitudinal component of RVEF. In patients with massive/torrential STR, the radial mechanism markedly deteriorates, leading to decreased global RVEF. The longitudinal component of RV motion demonstrated independent prognostic value in patients with STR.

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Ca2+ handling remodelling in a porcine model of right ventricular dysfunction

Increased afterload is the primary pathophysiologic mechanism for right ventricular failure (RVF), which is the most critical determinant of survival in patients with pulmonary hypertension (PH). The cellular and molecular processes involved in the RV remodeling, including Ca2+ handling as an instrumental actor in the heart, remain incompletely understood. We gain insights into the cellular Ca2+ signaling in a large animal model of RV failure, the chronic thromboembolic pulmonary hypertension (CTEPH) piglet model, to develop specific therapy targeting RVF. CTEPH piglet model consisted of a primary left pulmonary artery ligation followed by weekly embolization in the right lower lobe leading to PH and progressive RV hypertrophy and failure. After six weeks, the piglet model replicated all the features of human CTEPH: increased pulmonary vascular resistance, mean pulmonary arterial pressure (PAP), and RV wall thickness associated with RV dysfunction as assessed by the reduced tricuspid annular plane systolic excursion (TAPSE). RV histological analyses revealed hypertrophied cardiomyocytes and aberrant fibrosis. At the cell level, RV myocytes from CTEPH piglets presented reduced L-type Ca2+ currents and CACNA1C mRNA, lower and slower [Ca2+]i transients, decreased sarcoplasmic reticulum Ca2+ content, and cell shortening to myocytes from sham piglets. This was related to reduce Sarco/Endoplasmic Reticulum Ca2+-ATPase isoform 2a (SERCA2a) protein expression. We found that store-operated Ca2+ entry is increased in hypertrophied RV myocytes, which is correlated with a de novo expression of the SR Ca2+ sensor STIM1L (long stromal interacting molecule 1). Finally, we found that Ca2+ sparks are larger and longer in RV myocytes from CTEPH piglets, whereas their frequencies and amplitude were unchanged compared to myocytes from sham. This was associated with profound disorganization of T tubules and ryanodine receptors (RyR) clustering without changes in RyR phosphorylation status. Our data highlight a cellular Ca2+ cycling remodeling that participates to the pathogenesis of RVF in CTEPH piglets.

LCZ696 (sacubitril/valsartan) inhibits pulmonary hypertension induced right ventricular remodeling by targeting pyruvate dehydrogenase kinase 4

BackgroundRight 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). MethodsAdult 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. ResultsWe 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. ConclusionsPdk4 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.

Evaluation of right ventricular myocardial deformation properties in fetal hypoplastic left heart by two-dimensional speckle tracking echocardiography

PurposeRight ventricular (RV) function influences the outcome of hypoplastic left heart (HLH) patients. This study aimed to confirm the assumption of prenatal RV remodeling and possible influencing factors of myocardial restructuring using two-dimensional speckle tracking echocardiography (2D STE).MethodsThis is a retrospective cross-sectional cohort study including HLH fetuses and gestational age-matched controls. Based on a four-chamber view, cine loops were stored with 60 frames per second. Global longitudinal peak systolic strain (GLPSS) of the RV was retrospectively determined and compared to healthy controls. Furthermore, HLH subgroups were built according to the presence of left ventricular endocardial fibroelastosis (LV-EFE) and restrictive foramen ovale (FO) to investigate the effect of these compromising factors on myocardial deformation.ResultsA total of 41 HLH fetuses and 101 controls were included. Gestational age at fetal assessment was similarly distributed in both groups (controls: 26.0 ± 5.6 weeks vs. HLH: 29.1 ± 5.6 weeks). Relating to RV-GLPSS values, fetuses with HLH demonstrated lower mean values than healthy control fetuses (− 15.65% vs. − 16.80%, p = 0.065). Cases with LV-EFE (n = 11) showed significantly lower mean values compared to such without LV-EFE (n = 30) (RV-GLPSS: − 12.12% vs. − 16.52%, p = 0.003). No significant differences were observed for cases with FO restriction (n = 10).ConclusionsIn HLH the RV undergoes prenatal remodeling, leading to an adaptation of myocardial function to LV conditions. Further explorations by STE should expand knowledge about RV contraction properties in HLH and its impact on surgical outcome.

Comparison of Dacron Band versus Segmental Annuloplastyin Treatment of Tricuspid Valve Repair

Objective: The objective of this study was to compare outcome of Dacron Band versus Segmental Annuloplasty in treatment of TV repair. Study Design: This was a randomized controlled trial. Place and Duration: This study was conducted at the Cardiac surgery Department, PIC, Jail Road, Lahore from 25 October 2021 to 25 Oct, 2022. Methodology:A total of 148 patients were enrolled in this study and divided into two groups equally. For categorical data like gender, and grades of Tricuspid regurgitation, frequency and percentages was used. For quantitative data mean ± S.D was computed. P-value ≤ 0.05 was taken as significant. Results: The mean age of the cases in Group-A was 47.97 ± 8.29 and in Group-B was 51.01 ± 7.78. In our study post-operative RVEDD and TVPG found significant with p-value 0.044 and &lt;0.01 respectively. Similarly, the p-value of follow-up RVSTDI and RVEDD was statistically significant with p-value 0.03 and 0.007 respectively. Conclusion: Both Dacron band and segmental annuloplasty techniques are available for TV repair; however, dacron band placement in TV repair patients is associated with better RV remodelling, and as a result, a more likely improvement in right ventricular function and a better repair outcome are predicted. After tricuspid valve surgery, dacron band implantation is correlated with a lower incidence of TR recurrence and enhanced long-term event-free survival. As a result, this method in tricuspid valve surgery should be used more frequently. Keywords: Segmental Annuloplasty, Dacron Band, TR, TV repair

Comprehensive Ultrasound Imaging of Right Ventricular Remodeling Under Surgically Induced Pressure Overload in Mice.

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 weeks of age. Ultrasound imaging was conducted at 2, 4 and 8 weeks post-surgery using both classical and advanced ultrasound imaging modalities including 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 to the sham group. By applying 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 to the sham group. The PAC group also showed prolonged RV contraction, asynchronous inter-play between RV and left ventricle (LV), and passive leftward motion of the inter-ventricular 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.

Safety, efficacy, and clinical outcomes of transcatheter tricuspid valve replacement: One-year follow-up.

The aim was to evaluate the safety and efficacy of TTVR in patients with severe TR at the 1-year follow-up. This project was a single-center, observational study. From September 2020 to May 2021, 15 patients with severe or extremely severe TR at high risk of traditional surgery were enrolled. All patients had preoperative imaging assessments to evaluate the tricuspid valve and the anatomy of the right heart. All patients were planned to treated with the LuX-Valve (Ningbo Jenscare Biotechnology, Ningbo, China). The LuX-Valve was implanted under the intraoperative guidance of TEE and X-ray fluoroscopy. Data were collected at baseline, before discharge, and at 30 days, 6 months, and 1 year postoperatively. The LuX-Valves were successfully implanted in all 15 patients. TR was significantly reduced to ≤ 2 +. One patient died on postoperative day 12 of a pulmonary infection that was considered unrelated to the procedures or the devices. The remaining 14 patients (100.0%) reached the primary end point. One patient (7.1%) was rehospitalized during 1-year follow-up because of device thrombosis. The number of patients who survived at 1 year with New York Heart Association (NYHA) functional class II was higher than that before TTVR (11/14 vs. 0/15, P = 9.11 × 10-4). Patients with peripheral edema and ascites decreased from 100.0 to 46.7% at baseline to 28.6% and 14.3% at 1 year (P = 1.57 × 10-3 and 2.53 × 10-2). TTVR is associated with RV remodeling, increased cardiac output, and improvement in NYHA functional class. Using the LuX-Valve for TTVR to treat patients with severe TR is a feasible and relatively safe method with reliable clinical results. Further studies are needed to determine long-term outcomes.