Right Ventricular Systolic Function Research Articles

Associations Between Echocardiographic Right Heart Measurements With Short-Term Prognosis in Heart Failure: A Prospective Study.

Echocardiographic right ventricular (RV) dysfunction is a strong risk determinant for prognosis in patients with heart failure (HF). Although parameters of RV systolic function are widely used to define RV dysfunction, there is scarce data to suggest these parameters are best suited to predict HF-related outcomes. We aimed to understand which morphologic or functional parameters are most closely associated with short-term mortality and HF-related hospitalization in patients with HF. A total of 191 patients from eight study centers were included to this study. A detailed echocardiographic examination was done at enrollment, and patients were followed up for 6 months via direct interviews or phone calls. All right-sided echocardiographic parameters other than tricuspid annular plane systolic excursion were associated with outcomes. In a proportional hazards model that included right-heart parameters, RV longitudinal diameter (HR: 1.07, 95%CI: 1.04-1.10, p<0.001), wall thickness (HR: 1.3, 95%CI: 1.13-1.50, p<0.001), and tricuspid annular systolic velocity (HR: 0.90, 95%CI: 0.82-0.96, p=0.02) were found as the independent predictors. However, only RV longitudinal dimension (HR: 1.04, 95%CI: 1.01-1.08, p=0.01) and RV wall thickness (HR: 1.32, 95%CI: 1.10-1.60, p=0.004) were associated with short-term outcomes after adjusting for other clinical and left-sided echocardiographic variables. On a Bayesian logistic regression model that included right-sided echocardiography variables, there was strong evidence for including either RV longitudinal diameter (BF10: 190.4) or wall thickness (BF10: 30.7) to the final model. Parameters of RV morphology were better predictors of short-term outcomes in HF patients.

Características de la insuficiencia tricúspide grave inducida por dispositivos de estimulación intracardiacos

Introduction and aimsTricuspid regurgitation (TR) induced by the implantation of cardiac implantable electronic devices (CIED) is an increasingly common cause of severe TR. Our aim was to describe the echocardiographic phenotypic characteristics of CIED-induced severe TR. MethodsRetrospective cohort study that included patients with severe TR related to CIED diagnosed in the cardiac imaging unit of a Spanish tertiary hospital. Results37 patients with severe TR induced by lead/electrode interference formed our study group. TR was predominantly severe (68%), followed by massive (21%) and torrential (11%). The leaflet most affected by the interference was the septal. 58% of the sample presented severe dilatation of the right atrium (RA) (mean RA area 28cm2). Mean tricuspid annulus measurement was 42mm. The usual parameters for quantifying RV systolic function were on average within the normal range (TAPSE mean 19mm, S’ wave 10mm, FAC 41%), while global RV strain (RVGLS -15%) and free wall strain (RVFWLS -19%) were found reduced. An incipient degree of ventricular/pulmonary arterial uncoupling was evident (mean TAPSE/PSAP 0.34, SGLVD/PSAP 0.27%/mmHg). ConclusionsOur patients with CIED-induced severe TR are characterized by a heterogeneous phenotype with a high prevalence of severe RA and tricuspid annulus dilatation. RVGLS, RVFWLS, and arterial ventricular coupling were the most sensitive parameters for early assessment of RV systolic dysfunction.

Assessment of right ventricular sequelae by speckle tracking echocardiography in recovered COVID-19 patients

Background TTE is the main modality used to assess RV function, but conventional TTE parameters have limited diagnostic value because they may fail to detect early abnormalities in RV systolic function. Due to its ability to detect subclinical impairment of cardiac function, 2D STE has been widely used to investigate RV function. In this study, we aimed to investigate whether there are sequelae of RV function in recovered COVID-19 patients with pulmonary involvement. Methods This is a prospective observational cohort study of 57 healthy volunteers and 54 patients. Participants had no history of chronic illness and no evidence of respiratory or cardiac symptoms. The patients had been hospitalised with COVID-19 with pulmonary involvement but did not require intensive care unit follow-up or non-invasive mechanical ventilation support. TTE was performed. Demographic and clinical characteristics and laboratory test results were collected. Results LVEF, TAPSE, St and FAC were significantly lower in the patient group. LV-LS 3-chamber, LV-GLS, RV-FWS, RV-GLS were significantly lower in the patient group. Conclusions RV-LS and LV-GLS were shown to decrease in the patient group. Although no obvious pathological values were observed in RV parameters on conventional echocardiography, TAPSE, St and FAC values were lower in the patient group.

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.

Serial Changes in Ventricular Strain in Symptomatic Obstructive Hypertrophic Cardiomyopathy Treated With Mavacamten: Insights From the VALOR-HCM Trial.

In severely symptomatic patients with obstructive hypertrophic cardiomyopathy, VALOR-HCM (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy) demonstrated that mavacamten reduces the need for septal reduction therapy with sustained improvement in left ventricular (LV) outflow tract gradients and symptoms. Global longitudinal strain (GLS), a measure of regional myocardial function, is a more sensitive marker of systolic function. In VALOR-HCM, we assessed serial changes in LV and right ventricular (RV) strain. VALOR-HCM included 112 patients with symptomatic obstructive hypertrophic cardiomyopathy (mean, 60 years; 51% male; LV ejection fraction, 68%). Patients assigned to mavacamten at baseline continued the drug for 56 weeks (n=56) and those assigned to placebo (n=52) transitioned to mavacamten from weeks 16 to 56 (40-week exposure). LV-GLS and RV-GLS assessment was performed using a vendor-neutral software. Non-foreshortened apical (4-, 3-, and 2-chamber) views were used to obtain peak LV-GLS. RV focused 4-chamber view was used to calculate RV 4-chamber and free wall strain. A more negative strain value is favorable. At baseline, the mean LV-GLS, RV 4-chamber, and free wall strain values were -14.7%, -22.2%, and -16.8%, respectively (all worse than reported normal means). In the total study sample, LV-GLS significantly improved from baseline to week 56 (P=0.02). Twelve patients had transient reduction in LV ejection fraction (<50%) requiring temporary drug interruption (including 3 permanent discontinuations). The LV-GLS in this subgroup was worse at baseline versus total study population (-11.4%), with no significant worsening from baseline through week 56 (P=0.64). Both free wall and 4-chamber RV-GLS remained unchanged from baseline to week 56 (P=0.62 and P=0.56, respectively). In VALOR-HCM, treatment with mavacamten improved LV-GLS from baseline through week 56 (with no significant worsening of LV-GLS in patients with a reduction in LV ejection fraction ≤50%), suggesting a favorable long-term impact on regional LV systolic function. Additionally, there was no detrimental impact on RV systolic function. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04349072.

O07 RENAL DENERVATION IMPROVES RIGHT VENTRICULAR FUNCTION, RESTORES MYOCARDIAL NOREPINEPHRINE LEVELS AND REVERSES VENTRICULAR SPECIFICITY OF SELECTED MARKERS IN HYPERTENSIVE RATS WITH HEART FAILURE INDUCED BY VOLUME OVERLOAD

Background and objective: Despite the known anti-hypertensive effect of renal denervation (RDN), its influence on the cardiac function, particularly of the right ventricle (RV) and the cardiac sympathetic nervous system in heart failure (HF) is poorly understood. This study aimed to investigate the effect of RDN on RV function, myocardial norepinephrine (NE), and left versus right ventricular (LV/RV) dominance of HF markers in HF induced by aorto-caval fistula (ACF). Methods: ACF was created in hypertensive Ren-2 transgenic rats. RDN was performed by phenol application. Cardiac function was measured by echocardiography and pressure-volume analysis. NE levels were measured using an ELISA kit, protein expression was assessed by western blotting, gene expression by TaqMan PCR assay, and ROS by Amplex Red assay. Results: RDN in ACF rats decreased RV hypertrophy and dilatation, decreased RV end-systolic pressure and end-diastolic pressure, improved RV function (Ees +45%, FAC +20%), decreased HF gene markers Nppa, Tgm2, Myh7/6 ratio, and increased SOD2 protein expression. RDN decreased plasmatic NE levels, increased NE in RV, and decreased monoamine oxidase (MAO-A) in RV. NE levels and SOD2 were more dominant in RV than LV in control (sham/intact) rats and ACF changed their specificity towards RV dominance, while RDN had no effect in these parameters in ACF on ventricular specificity. In sham/intact rats dominant for LV were hemodynamic parameters Ees, EDPVR, and molecular markers Mao-a, ROS production by MAO-A, Nppa, Myh7, Myh7/6 ratio, Tgm2, Uchl1, and Beta1/Chrm2 ratio. ACF changed the dominance of these selected markers from LV to RV. Interestingly, RDN reversed dominance back towards LV in gene markers Mao-a, Nppa, Myh7, Tgm2, Uchl1, and Beta1/Chrm2 ratio. Conclusions: RDN decreased RV ESP and EDP, improved RV systolic function, restored NE levels, decreased RV gene expression of selected HF markers, and reversed their RV/LV dominance, probably by reduction of central sympathetic nerve drive and alternations of the cardiac sympathetic nervous system.

Intraoperative right ventricular end-systolic pressure–volume loop analysis in patients undergoing cardiac surgery: A proof-of-concept methodology

BackgroundPerioperative right ventricular (RV) dysfunction is associated with increased morbidity and mortality in cardiac surgery patients. This study aimed to demonstrate proof of concept in generating intraoperative RV pressure–volume (PV) loops and conducting an end-systolic PV relationship (ESPVR) analysis using data obtained from routinely used intraoperative monitors. MethodsAdult patients undergoing cardiac surgery with the placement of a pulmonary artery catheter (PAC) between May 2023 and March 2024 were included prospectively. The PV loops were generated using 3-dimensional echocardiographic RV volume data and continuous RV pressure data obtained from a PAC. The volume–time and pressure–time curves were digitized using the semiautomatic WebPlotDigitizer program and synchronized to reconstruct an RV PV loop and analyze ESPVR using the previously validated single-beat method. ResultsIntraoperative RV PV loops were generated for 25 patients, including 17 patients with preserved RV systolic function (group 1) and 8 patients with reduced systolic function (group 2). Mean Ees, Ea, and Ees/Ea ratio were 0.63 ± 0.25 mm Hg/mL, 0.60 ± 0.23 mm Hg/mL, and 1.0 8 ± 0.31 mm Hg/mL, respectively, by the Pmax method and 0.56 ± 0.32 mm Hg/mL, 0.60 ± 0.23 mm Hg/mL, and 0.91 ± 0.21 mm Hg/mL, respectively, by the V0 method. Group 1 had a significantly higher Ees compared to group 2 regardless of the calculation method and a larger Ees/Ea ratio calculated by the V0 method. ConclusionsIt is clinically feasible to derive RV PV loops from routine hemodynamic and echocardiographic data. With further validation and technological support, this can be a potential real-time intraoperative RV function monitoring tool.

The impact of spinal anesthesia on cardiac function in euvolemic vascular surgery patients: insights from echocardiography and biomarkers.

Existing evidence of the effect of spinal anesthesia (SA) on cardiac systolic function is scarce and inconclusive. This study aimed to evaluate the effects induced by a single injection of SA for elective vascular surgery on left (LV) and right (RV) ventricular systolic performance using transthoracic echocardiography (TTE). A prospective study. Single-center study, university hospital. Adult patients undergoing elective vascular surgery with SA. During patients' evaluations fluid administration was targeted using arterial waveform monitoring. All patients underwent TTE studies before and after SA induction for the assessment of indices reflective of LV and RV systolic function. Blood samples were drawn to measure troponin and brain natriuretic peptide (BNP) levels. A total of 62 patients (88.7% males, 71.00 ± 9.42 years) were included in the study. The primary outcome was the difference before and after SA in LV ejection fraction (LVEF) and tricuspid annular plane systolic excursion (TAPSE). In total population, LVEF significantly increased after SA 53.07% [16.51]vs 53.86% [13.28]; p < 0.001). End-systolic volume (ESV, 69.50 [51.50] vs. 65.00 [29.50] ml; p < 0.001) decreased while stroke volume (SV) insignificantly increased (70.51 ± 16.70 vs. 73.00 ± 18.76ml; p = 0.131) during SA. TAPSE remained unchanged (2.23 [0.56] vs. 2.25 [0.69] mm; p = 0.558). In patients with impaired compared to those with preserved LV systolic function, the changes evidenced in LVEF (7.49 ± 4.15 vs. 0.59 ± 2.79; p < 0.001), ESV (-18.13 ± 18.20 vs-1.53 ± 9.09; p < 0.001) and SV (8.71 ± 11.96 vs-1.43 ± 11.89; p = 0.002) were greater. This study provides evidence that SA in patients undergoing elective vascular surgery improved LV systolic function, while changes in RV systolic function are minimal.

Impact of regional anesthesia on left and right ventricular performance after off-pump coronary artery bypass grafting: randomized controlled study

Introduction. New anesthesia techniques require evidence of the safety of their implementation, however there is still the opinion about negative impact of regional anesthesia on heart performance and central hemodynamics. The objective of our study was to evaluate effect of regional anesthesia on systolic and diastolic myocardial function in off-pump coronary artery bypass grafting (OPCAB).Materials and methods. A prospective randomized controlled trial included 45 patients who underwent elective OPCAB, equally divided into 3 groups – general anesthesia in combination with epidural anesthesia (GA+EA), general anesthesia with erector spinae plane block (GA+ESPB) and general anesthesia without regional anesthesia (GA). The systolic function of the left (LV) and right ventricle (RV), as well as the diastolic function of the LV were evaluated during five stages perioperatively, using echocardiography and thermodilution via Swan-Ganz catheter.Results. There were no intergroup differences in parameters of LV or RV systolic function and LV diastolic function during study stages. Perioperatively, there was a decrease in LV end-diastolic volume in the groups of OA+ESPB (p = 0.001) and OA (p = 0.003).At the end of the first postoperative day (POD), pulmonary artery wedge pressure decreased in the groups of OA+EA (p = 0.003) and OA+ESPB (p = 0.008); meanwhile, ejection time (p = 0.003) and velocity-time integral (p = 0.005) from RV reduced only in the OA+ESPB group. In the OA+EA group at the end of POD1, the reservoir strain of left atrium (p = 0.022) and isovolumic relaxation time (p = 0.006) decreased.Conclusion. In OPCAB, epidural anesthesia and ESPB do not result in deterioration of LV systolic and diastolic function and do not have a negative impact on the RV.

Fetal Right Heart Strain in Systemic Right Ventricles and Impact on Post-surgical Outcomes.

Patients with hypoplastic left heart syndrome (HLHS) and its variants rely on the right ventricle (RV) to provide cardiac output. Diminished RV systolic function has been associated with poor clinical outcomes in this population. Echocardiographic strain has emerged as a useful method to quantify RV deformation. We aimed to describe fetal strain in the systemic RV and further investigate if there was any correlation with clinical outcomes. We conducted a retrospective, single center study evaluating strain in fetuses with systemic RV. We measured fetal RV global longitudinal strain (GLS) and segmental strain using Tomtec 2D speckle tracking software and compared these findings to controls. Fifty patients with systemic RV were included in the study group with controls matched one to one for each echocardiogram. Ten patients died after first-stage palliation. GLS was reproducible, with interobserver ICC 0.82. There was no statistically significant difference in GLS among different HLHS subtypes. Abnormal GLS did not correlate with worse clinical outcomes. GLS in systemic RVs in the 2nd and 3rd trimester did not vary significantly throughout gestation and did not correlate with clinical outcomes. Risk factors associated with poor outcome were mainly postnatal. Multi-centered studies are needed to determine if these findings hold true in a larger sample size.

Assessment of right ventricular systolic function using speckle tracking strain imaging in patients with severe tricuspid regurgitation: a validation study with cardiac magnetic resonance

BackgroundRight ventricular (RV) systolic dysfunction is an established prognostic factor in patients with severe tricuspid regurgitation (TR). However, accurate assessment of RV systolic function using conventional echocardiography remains challenging. We investigated the accuracy of strain measurement using speckle tracking echocardiography (STE) for evaluating RV systolic function in patients with severe TR.MethodsWe included consecutive patients with severe TR who underwent echocardiography and cardiac magnetic resonance imaging (CMR) within 30 days between 2011 and 2023. Two-dimensional STE was used to measure RV free wall longitudinal strain (RVFWLS) and global longitudinal strain (RVGLS). These values were compared with the RV ejection fraction (RVEF) from CMR. RV systolic dysfunction was defined as a CMR-derived RVEF < 35%.ResultsA total of 87 patients with severe TR were identified during the study period. Among echocardiographic RV strain measurements, RVFWLS was the best correlate of CMR-derived RVEF (r = –0.37, P < 0.001), followed by RVGLS (r = –0.27, P = 0.012). Receiver operating characteristic (ROC) curve analysis revealed that RVFWLS provided better discrimination of RV systolic dysfunction, yielding an area under the ROC curve (AUC) of 0.770 (95% confidence interval [CI], 0.696–0.800) than RV fractional area change (AUC, 0.615; 95% CI, 0.500–0.859).ConclusionsIn patients with severe TR, STE-derived RVFWLS showed the best correlation with RVEF on CMR and displayed superior discrimination of RV systolic dysfunction compared with the RV fractional area change. This study suggests the potential usefulness of STE in assessing RV systolic function in this population.

Abstract Tu057: Renal denervation enhances right ventricular function, reduces myocardial damage, and restores myocardial sympathetic signaling in rats with heart failure induced by volume overload

Introduction: Heart failure (HF) is associated with chronically increased sympathetic nervous activity with depleted norepinephrine (NE) in the myocardium. Despite the known anti-hypertensive effect of renal denervation (RDN), its influence on the function of the right ventricle (RV) and the cardiac sympathetic nervous system in HF is not well comprehended. Hypothesis: RDN improves RV function by reducing central sympathetic drive and changes of a sympathetic nervous branch in the heart. Aims: To investigate the effect of RDN on RV function, HF markers, myocardial NE, and its metabolism in RV in HF induced by aorto-caval fistula (ACF). Methods: HF was induced by ACF in Ren-2 transgenic rats (TGR). One week later, the RDN was performed by phenol application. Two weeks after RDN, RV function was measured by pressure-volume analysis and RV tissue was collected. Echocardiography was done once a week, during the entire experiment. NE levels were measured using an ELISA kit, protein expression was assessed by western blotting, gene expression by TaqMan PCR gene expression assay, and ROS by oxidation of Amplex Red assay. Results: The ACF increased RV weight, RV dimensions (RVD1, RVD2, RVD3), end-systolic (ESP) and end-diastolic pressure (EDP), reduced RV systolic function (end-systolic elastance - Ees, fractional area change - FAC) and ventricular-arterial coupling (Ees/Ea ratio), increased gene expression of HF markers collagen I/III ratio, natriuretic peptide A (Nppa), myosine heavy chain 7/6 (Myh7/6) ratio, transglutaminase 2 (Tgm2), and decreased superoxide dismutase 2 (SOD2) protein expression. ACF increased plasmatic NE levels, depleted NE in RV, decreased tyrosine hydroxylase protein expression in RV, and increased gene, protein expression, and activity of monoamine oxidase A (MAO-A). RDN decreased RV hypertrophy and dilatation (RVD1, RVD2, RVD3), decreased RV ESP (-7 mmHg, p=0.004) and EDP (-2.2 mmHg, p=0.003), improved RV function (Ees +45%, p=0.03, FAC +20%, p=0.005, Ees/Ea ratio +46%, p=0.02), decreased HF markers collagen I/III ratio, Nppa, Tgm2, Myh7/6 ratio, and increased SOD2 protein expression. RDN decreased plasmatic NE levels, increased NE in RV (+32%, p=0.03), and decreased MAO-A in RV. Conclusions: RDN decreased RV ESP and EDP, improved RV systolic function, restored NE levels, and decreased RV gene expression of selected HF markers, probably by reduction of central sympathetic nerve drive and alterations of the cardiac sympathetic nervous system.

Abstract Tu051: ROR2 Drives Right Ventricular Failure Via Proteostatic Imbalances

Background: No therapies exist to treat right ventricular failure (RVF), in part because RVF molecular drivers have been incompletely studied. We recently identified that the developmentally restricted noncanonical WNT receptor ROR2 is re-expressed in a severity-dependent manner in human RVF. Here we test in mice if, and how, the re-expression of Ror2 causes RVF. Methods/Results: We find in neonatal rat ventricular myocytes (NRVMs) that Ror2 overexpression (Ror2 OE ) both activates protein translation and reduces Hspa1a/b mRNA and Hsp70 protein, resulting in increased protein turnover, fragmented sarcomeres, intercalated disc disruption, reduced cell major axis, impairment of contractile and relaxation kinetics, and ectopy. Ror2 knockdown (Ror2 KD ) results in opposing phenotypes. Hsp70 overexpression or proteasome inhibition rescues many of the Ror2 OE phenotypes, demonstrating their causal involvement. NRVM proteomic analysis indicates that Ror2 OE activates an ERK/p90RSK/Eef2 pathway that is known to regulate translation extension. In vivo, cardiac Ror2 OE in mice causes RV dilation and dysfunction, intercalated disc disruption, reduced Hspa1b (encoding for Hsp70), proteasome activation, and reduced cardiomyocyte ubiquitin staining. The mouse pulmonary artery banding (PAB) model of RVF reveals similar Ror2 induction and proteasome activation. Ror2 KD by AAV9 in PAB reduces RV dilation and improves RV systolic and diastolic function. Finally, in cardiac samples from human RVF, we find evidence for a similar ROR2-responsive proteostatic imbalance with increased proteasome activity and ubiquitin as well as markers of increased ERK and p90RSK. Conclusions: ROR2 is induced in human and mouse RVF, and mechanistic studies in NRVMs and mice show that the induction of ROR2 causes RVF by disrupting the proteostatic balance of translation, folding, and turnover. Knockdown or suppression of ROR2 may serve as a novel RVF therapeutic target.

Abstract Tu059: Single-Nucleus Transcriptomics Demonstrates Endothelial Cell Expansion in Failing Human Right Ventricles

Background: Right ventricular failure (RVF) is most commonly observed as a sequela of left ventricular failure (LVF)—for which it more than doubles the risk of mortality. Moreover, isolated RVF is the most common cause of death in pulmonary hypertension and is a leading cause of major adverse events in systemic right ventricle congenital heart diseases. Therapies which effectively treat LVF show poor efficacy for RVF. For example, beta blockade, a cornerstone of LVF therapy, has no efficacy in RVF. Therefore, there is a need for broader exploratory research to identify pathways which are dysregulated in RVF and which could serve as targets for future therapies. Methods/Results: To this end, we performed single-nucleus RNA sequencing (N=11) on RV myocardium from nonfailing or dilated cardiomyopathy (DCM) hearts subgrouped by preserved systolic and diastolic RV function (pRV) or RVF. After cell-type assignment and differential expression analysis, we find a progressive upregulation of pro-angiogenic signaling in vascular endothelial cells (ECs) from nonfailing to pRV and RVF. There is a concomitant expansion of the EC pool from nonfailing to pRV and RVF (EC percentage 5%, 9%,15% for NF, pRV, and RVF; p &lt; 0.05 for one-way ANOVA). We find increased HIF-mediated and VEGF-mediated signaling in these ECs, which may be mediating this expansion. Surprisingly, there is also increased expression of genes regulated by type 1 interferon signaling, which is thought to be anti-angiogenic. Discussion: In summary, we have conducted a single-nuclei transcriptomic study of human RVF and found evidence for increased angiogenic signaling and EC expansion. These findings are significant, as the balance of pro-angiogenic and anti-angiogenic factors in RVF is still unclear, with studies in animal models showing conflicting results in terms of changes in macro/microvasculature in RVF. Here, we provide evidence that in human RVF the balance tends to lead toward a pro-angiogenic phenotype, even in dysfunctional RVs. Orthogonal studies to validate the causal nature of these observed changes in pathogenesis of RVF are currently ongoing.

Abstract Tu065: The role of heavy metals in pulmonary arterial hypertension pathogenesis

Pulmonary arterial hypertension (PAH) is a disease where chronic high pulmonary arterial pressure causes inflammation, remodeling, and dysfunctions of lung endothelial/smooth muscle cells, and right ventricle (RV) cardiomyocytes. Pathogenesis is caused by a mixture of genetic, epigenetic, and environmental factors. Our clinical studies found PAH patients had elevated cadmium (Cd) and antimony (Sb) levels in the blood and/or urine, which correlated with increased severity of PAH parameters. Thus, we hypothesize that environmental factors, specifically chronic heavy metal exposure, could contribute to PAH pathogenesis either directly or indirectly. We tested if Cd could induce PAH or worsen PAH parameters in the mouse SU5416 and hypoxia (SuHx) PAH model. Forty male C57/6J mice were initially split in 2 groups: control and 5ppm Cd in drinking water (n=20/each) for 8 weeks (wks). Diastolic and systolic functions were evaluated with echocardiography (echo) at baseline, and 8ks. Then, half of these mice were subject to PAH induction, netting 4 subgroups (n=10/group): CTRL, Cd, PAH, and Cd+PAH. Echo was performed again 4 wks post-PAH induction, followed by RV systolic pressure (RVSP) measurement (n=3/group). The remaining 7 mice/group were euthanized for heart/lung histopathology focusing on fibrosis and hypertrophy, and protein western blot analyses. GraphPad Prism 8 software was used for statistical analysis with normality checked. When data did not follow normality, the non-parametric equivalence was used. Two-way and one-way ANOVA with Tukey were performed for echo/RVSP and histological/biochemical analyses respectively, with a p-value&lt;0.05 being significant. Results showed 12-wks Cd exposure alone caused: (1) significantly increased RV systolic function indicating systolic stimulation, and (2) significantly increased collagen contents in both ventricles and LV cardiomyocyte area when compared to CTRL. Twelve-wks Cd+PAH group demonstrated (1) significantly decreased RV cardiac output and RVSP measurements indicating RV failure; (2) no further RV changes in collagen contents or hypertrophy; (3) LV western blot analysis revealed significant upregulation of antioxidant proteins, including catalase and superoxide dismutase 2, when compared to PAH group. Further mechanistic experiments are being conducted, including whether Sb has similar results as Cd.

Sex-dependent remodeling of right ventricular function in a rat model of pulmonary arterial hypertension.

Right ventricular (RV) function is an important prognostic indicator for pulmonary arterial hypertension (PAH), a vasculopathy that primarily and disproportionally affects women with distinct pre- and postmenopausal clinical outcomes. However, most animal studies have overlooked the impact of sex and ovarian hormones on RV remodeling in PAH. Here, we combined invasive measurements of RV hemodynamics and morphology with computational models of RV biomechanics in sugen-hypoxia (SuHx)-treated male, ovary-intact female, and ovariectomized female rats. Despite similar pressure overload levels, SuHx induced increases in end-diastolic elastance and passive myocardial stiffening, notably in male SuHx animals, corresponding to elevated diastolic intracellular calcium. Increases in end-systolic chamber elastance were largely explained by myocardial hypertrophy in male and ovary-intact female rats, whereas ovariectomized females exhibited contractility recruitment via calcium transient augmentation. Ovary-intact female rats primarily responded with hypertrophy, showing fewer myocardial mechanical alterations and less stiffening. These findings highlight sex-related RV remodeling differences in rats, affecting systolic and diastolic RV function in PAH.NEW & NOTEWORTHY Combining hemodynamic and morphological measurements from male, female, and ovariectomized female pulmonary arterial hypertension (PAH) rats revealed distinct adaptation mechanisms despite similar pressure overload. Males showed the most diastolic stiffening. Ovariectomized females had enhanced myocyte contractility and calcium transient upregulation. Ovary-intact females primarily responded with hypertrophy, experiencing milder passive myocardial stiffening and no changes in myocyte shortening. These findings suggest potential sex-specific pathways in right ventricular (RV) adaptation to PAH, with implications for targeted interventions.

Correlation between worsening pneumonitis and right ventricular systolic function in critically ill patients with COVID-19

BackgroundThe pneumonitis associated with coronavirus disease 2019 (COVID-19) infection impacts the right ventricle (RV). However, the association between the disease severity and right ventricular systolic function needs elucidation.MethodWe conducted a retrospective study of 108 patients admitted to critical care with COVID-19 pneumonitis to examine the association between tricuspid annular plane systolic excursion (TAPSE) by transthoracic echocardiography as a surrogate for RV systolic function with PaO2/FiO2 ratio as a marker of disease severity and other respiratory parameters.ResultsThe median age was 59 years [51, 66], 33 (31%) were female, and 63 (58%) were mechanically ventilated. Echocardiography was performed at a median of 3 days [2, 12] following admission to critical care. The PaO2/FiO2 and TAPSE medians were 20.5 [14.4, 32.0] and 21 mm [18, 24]. There was a statistically significant, albeit weak, association between the increase in TAPSE and the worsening of the PaO2/FiO2 ratio (r2 = 0.041, p = 0.04). This association was more pronounced in the mechanically ventilated (r2 = 0.09, p = 0.02). TAPSE did not correlate significantly with FiO2, PaO2, PaCO2, pH, respiratory rate, or mechanical ventilation. Patients with a TAPSE ≥ 17 mm had a considerably worse PaO2/FiO2 ratio than a TAPSE < 17 mm (18.6 vs. 32.1, p = 0.005). The PaO2/FiO2 ratio predicted TAPSE (OR = 0.94, p = 0.004) with good area under the curve (0.72, p = 0.006). Moreover, a PaO2/FiO2 ratio < 26.7 (moderate pneumonitis) predicted TAPSE > 17 mm with reasonable sensitivity (67%) and specificity (68%).ConclusionIn patients admitted to critical care with COVID-19 pneumonitis, TAPSE increased as the disease severity worsened early in the course of the disease, especially in the mechanically ventilated. A TAPSE within the normal range is not necessarily reassuring in early COVID-19 pneumonitis.

Cardiac remodelling during pregnancy in women with congenital heart disease and systemic left ventricle.

Women with congenital heart disease (CHD) are at risk of pregnancy-related adverse outcomes (PRAO). The purpose of this study was to assess temporal changes in cardiac structure and function (cardiac remodelling) during pregnancy, and the association with PRAO in women with CHD. Retrospective study of pregnant women with CHD and serial echocardiograms (2003-2021). Cardiac structure and function were assessed at pre-specified time points: prepregnancy, early pregnancy, late pregnancy, and postnatal period. PRAO was defined as the composite of maternal cardiovascular, obstetric, and neonatal complications. The study comprised 81 women with CHD (age, 29 ± 5 years). Compared to the baseline echocardiogram, there was a relative increase in right ventricular systolic pressure (RVSP) (relative change 13 ± 5%, P < 0.001, in early pregnancy; and 18 ± 5%, P < 0.001, in late pregnancy). There was a relative decrease in right ventricle free wall strain (RVFWS) (relative change -11 ± 3%, P < 0.001, in late pregnancy; and -11 ± 4%, P = 0.003, in postnatal period), and a relative decrease in RVFWS/RVSP (relative change, -10 ± 5%, P = 0.02 in early pregnancy, -26 ± 7%, P < 0.001, in late pregnancy, and -14 ± 5%, P < 0.001, in postnatal period). Baseline right ventricular to pulmonary arterial (RV-PA) coupling, and temporal change in RV-PA coupling were associated with PRAO, after adjustment for maternal age and severity of cardiovascular disease. Women with CHD had a temporal decrease in RV systolic function and RV-PA coupling, and these changes were associated with PRAO. Further studies are required to delineate the aetiology of deterioration in RV-PA coupling during pregnancy, and the long-term implications of right heart dysfunction observed in the postnatal period.

Association Between Right Ventricular Systolic Parameters Measured by Echocardiography and Stroke Volume Derived From Pulmonary Artery Catheter in Ischemic Cardiogenic Shock

Objective: To determine the right ventricular (RV) systolic function echocardiographic parameter best associated with native stroke volume (SV) by thermodilution via pulmonary artery catheter (PAC) in patients admitted to intensive care with ST-elevation myocardial infarction (STEMI) complicated by cardiogenic shock (CS).Design, Setting, and Participants: Observational cohort study of 43 prospectively identified patients admitted to a tertiary cardiac intensive care unit in London, UK.Interventions: Simultaneous collection of comprehensive transthoracic echocardiographic, clinical, and PAC-derived hemodynamic data. Seven RV systolic function parameters were correlated with the PAC-derived SV.Measurements and Main Results: The median age was 61 [52, 67], and 36 patients (84%) were male. The median PAC-derived SV and LVEF were 57 ml [39, 70] and 31% [22, 35], respectively. The RV outflow tract velocity time integral (RVOT VTI) and tricuspid plane systolic excursion (TAPSE) correlated significantly with the PAC-derived SV (r = 0.42, p = 0.007, r = 0.37, p = 0.02, respectively). The RVOT VTI was independently associated with and predicted low PAC-derived SV (OR = 1.3, p = 0.03) with a good area under the curve (AUC = 0.71, p = 0.02). The RVOT VTI < 12.7 cm predicted low PAC-derived SV with a sensitivity of 66% and specificity of 72%.Conclusion: RVOT VTI is the echocardiographic RV systolic function parameter that best correlates with PAC-derived native SV in patients with STEMI complicated by CS. This parameter can help guide the hemodynamic management of this cohort.

Effects of Implantable Cardioverter-Defibrillator Leads on the Tricuspid Valve and Right Ventricle: A Randomized Trial

BackgroundThere are no randomized data to inform the extent to which transvenous cardiac leads cause tricuspid regurgitation (TR). ObjectivesThis study sought to determine the effect of a transvenous implantable cardioverter-defibrillator (TV-ICD) on TR severity, and secondarily, on right ventricular (RV) size and function. MethodsWe evaluated TR severity before and 6 months after implantable cardioverter-defibrillator insertion in a post hoc analysis of adults randomized to receive a transvenous (n = 252) or subcutaneous implantable cardioverter-defibrillator (S-ICD) (n = 251) device. TR and RV size and systolic function were assessed by echocardiographic images analyzed in a core laboratory. ResultsAt baseline, at least mild TR was present in 30% of individuals. At 6 months, the proportion of participants with any TR in the TV-ICD group was 42% vs 19% in the S-ICD group (P < 0.001). The proportion with moderate or severe TR was 7% in the TV-ICD group vs 2% in the S-ICD group (P = 0.021). At 6 months, the OR of at least 1 grade worsening of TR in the TV-ICD group as compared with the S-ICD group was 7.2 (95% CI: 3.3-15.8; P < 0.001). There were no differences between groups with respect to RV size or systolic function. ConclusionsSix months following TV-ICD insertion, there was a 7-fold increase in the risk of at least 1 grade worsening of TR, with 7% of individuals having TR that was moderate or severe. There was no detectable difference in RV size or function; however, longer follow-up is needed.