Myocardium Of Right Ventricle Research Articles

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 < 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.

Ventricular Angiography: A Forgotten Diagnostic Tool?

A 76-year-old male patient presented to the emergency room with acute decompensated right heart failure and presyncope episodes. Upon admission, his electrocardiogram (ECG) showed sustained monomorphic ventricular tachycardia at 180 bpm, which was electrically cardioverted, and the patient was subsequently admitted to the intensive care unit. The echocardiography showed a very dilated right ventricle (RV) with global systolic dysfunction and akinetic anterior and lateral walls. The coronary angiography was normal. The cardiac magnetic resonance showed signs of fibro-fatty replacement of the RV myocardium. Furthermore, the ECG after cardioversion showed inverted T waves and an epsilon wave in V1-V3 leads and late potentials by signal-averaged ECG. As such, a diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) was suspected. However, he presented no familial history of ARVC, was 76 years of age at the time of diagnosis and was asymptomatic until now. Given these considerations, we performed a right ventricular angiography which showed dilatation of the RV with akinetic/dyskinetic bulging, creating the "pile d'assiettes" image suggestive of ARVC. In the case of this patient, the RV angiography contributed to establish a diagnosis of ARVC with a very late presentation, to our knowledge the latest presentation in terms of age described in the literature.

Automated biventricular quantification in patients with repaired tetralogy of Fallot using a 3D deep learning segmentation model

BackgroundDeep learning is the state-of-the-art approach for automated segmentation of the left ventricle (LV) and right ventricle (RV) in cardiac magnetic resonance (CMR) images. However, these models have been mostly trained and validated using CMR datasets of structurally normal hearts or cases with acquired cardiac disease, and are therefore not well-suited to handle cases with congenital cardiac disease such as tetralogy of Fallot (TOF). We aimed to develop and validate a dedicated model with improved performance for LV and RV cavity and myocardium quantification in patients with repaired TOF. MethodsWe trained a 3D convolutional neural network (CNN) with 5-fold cross-validation using manually delineated end-diastolic (ED) and end-systolic (ES) short-axis image stacks obtained from either a public dataset containing patients with no or acquired cardiac pathology (n=100), an institutional dataset of TOF patients (n=96), or both datasets mixed. Our method allows for missing labels in the training images to accommodate for different ED and ES phases for LV and RV as is commonly the case in TOF. The best performing model was applied to all frames of a separate test set of TOF cases (n=36) and ED and ES phases were automatically determined for LV and RV separately. The model was evaluated against the performance of a commercial software (suiteHEART®, NeoSoft, Pewaukee, Wisconsin, US). ResultsTraining on the mixture of both datasets yielded the best agreement with the manual ground truth for the TOF cases, achieving a median DICE similarity coefficient of (93.8%, 89.8%) for LV cavity and of (92.9%, 90.9%) for RV cavity at (ED, ES) respectively, and of 80.9% and 61.8% for LV and RV myocardium at ED. The offset in automated ED and ES frame selection was 0.56 and 0.89 frames on average for LV and RV respectively. No statistically significant differences were found between our model and the commercial software for LV quantification (two-sided Wilcoxon signed rank test, p<5%), while RV quantification was significantly improved with our model achieving a mean absolute error of 12ml for RV cavity compared to 36ml for the commercial software. ConclusionWe developed and validated a fully automatic segmentation and quantification approach for LV and RV, including RV mass, in patients with repaired TOF. Compared to a commercial software, our approach is superior for RV quantification indicating its potential in clinical practice.

Abstract 18520: Impaired Ubiquitin-Proteasome Function in Right Ventricular Myocardium Correlates to Postoperative Outcomes in Tetralogy of Fallot

Introduction: At the time of initial repair, patients with Tetralogy of Fallot (TOF) undergo a sudden shift from a pressure to volume loaded right ventricle (RV). It is difficult to predict how TOF RVs will respond to this hemodynamic transition. Identifying mechanisms and targets may enable interventions to improve outcomes. Hypothesis: RV myocardial gene expression profiles at the time of TOF repair correlate to pre- and early postoperative clinical outcomes. Methods: RNAseq was performed from RV myocardium resected at the time of initial TOF repair (n=44). Gene expression profiling was performed using a weighted gene correlation network analysis (WGCNA) against pre- and post-op clinical variables. Mouse pulmonary artery band (PAB, n=9) stratified by degree of RV dilation was used to correlate pathways. Results: WGCNA identified a gene module that was associated with younger age at repair and worse TOF postop outcomes (prolonged milrinone, decreased right atrial and right ventricular strain) without a concomitant association with preop oxygen saturation. Biological process gene-set enrichment analysis using the 2023 Gene Ontology library revealed enrichment of regulators for ubiquitination, cell cycle/mitosis, DNA repair, microtubule polymerization, and Rho/GTPase. PAB mouse RV demonstrated a RV-dilation severity-dependent increase in bound ubiquitin (R 2 =0.61, p=0.01) and loss of free ubiquitin (R 2 =0.72, p=0.004; Figure). Conclusions: WGCNA reveals a RV myocardial gene expression profile that is associated with preoperative characteristics and early postoperative outcomes, and which is enriched for ubiquitination regulators. The PAB mouse recapitulates a severity-dependent increase in bound ubiquitin and loss of free ubiquitin which is consistent with literature suggesting proteostatic dysfunction and accumulation of misfolded proteins in RVF. Targeting proteostatic disruption prior to TOF repair may improve postoperative outcomes.

Differences in Mechanical, Electrical and Calcium Transient Performance of the Isolated Right Atrial and Ventricular Myocardium of Guinea Pigs at Different Preloads (Lengths)

There are only a few studies devoted to the comparative and simultaneous study of the mechanisms of the length-dependent regulation of atrial and ventricular contractility. Therefore, an isometric force-length protocol was applied to isolated guinea pig right atrial (RA) strips and ventricular (RV) trabeculae, with a simultaneous measurement of force (Frank–Starling mechanism) and Ca2+ transients (CaT) or transmembrane action potentials (AP). Over the entire length-range studied, the duration of isometric contraction, CaT and AP, were shorter in the RA myocardium than in the RV myocardium. The RA myocardium was stiffer than the RV myocardium. With the increasing length of the RA and RV myocardium, the amplitude and duration of isometric contraction and CaT increased, as well as the amplitude and area of the “CaT difference curves” (shown for the first time). However, the rates of the tension development and relaxation decreased. No contribution of AP duration to the heterometric regulation of isometric tension was found in either the RA or RV myocardium of the guinea pig. Changes in the degree of overlap of the contractile proteins of the guinea pig RA and RV myocardium mainly affect CaT kinetics but not AP duration.

Differences in Effects of Length-Dependent Regulation of Force and Ca2+ Transient in the Myocardial Trabeculae of the Rat Right Atrium and Ventricle.

The comparative differences in the fundamental mechanisms of contractility regulation and calcium handling of atrial and ventricular myocardium remain poorly studied. An isometric force-length protocol was performed for the entire range of preloads in isolated rat right atrial (RA) and ventricular (RV) trabeculae with simultaneous measurements of force (Frank-Starling mechanism) and Ca2+ transients (CaT). Differences were found between length-dependent effects in RA and RV muscles: (a) the RA muscles were stiffer, faster, and presented with weaker active force than the RV muscles throughout the preload range; (b) the active/passive force-length relationships were almost linear for the RA and RV muscles; (c) the value of the relative length-dependent growth of passive/active mechanical tension did not differ between the RA and RV muscles; (d) the time-to-peak and amplitude of CaT did not differ between the RA and RV muscles; (e) the CaT decay phase was essentially monotonic and almost independent of preload in the RA muscles, but not in the RV muscles. Higher peak tension, prolonged isometric twitch, and CaT in the RV muscle may be the result of higher Ca2+ buffering by myofilaments. The molecular mechanisms that constitute the Frank-Starling mechanism are common in the rat RA and RV myocardium.

Myocardial extracellular volume is a non-invasive tissue marker of heart failure in patients with transposition of the great arteries and systemic right ventricle.

Focal myocardial fibrosis in the systemic right ventricle (RV) is related to ventricular dysfunction and adverse outcome in patients with d-transposition of the great arteries (dTGA) post atrial redirection and those with congenitally corrected TGA (ccTGA). The role of diffuse fibrotic lesions in these conditions remains poorly understood. Our study aimed to investigate diffuse myocardial fibrosis by measuring extracellular volume (ECV) with cardiovascular magnetic resonance (CMR) and to explore correlations between ECV and clinical as well as functional markers of heart failure in patients with TGA and systemic RV. We prospectively included dTGA and ccTGA patients aged ≥14 years and compared them to healthy controls. Standardized CMR included modified Look-Locker Inversion recovery T1 mapping to quantify diffuse myocardial fibrosis in the systemic RV and the subpulmonary left ventricle (LV). The centerline of RV and LV myocardium was marked with a line of interest tool to determine native and post-contrast T1 for quantification of ECV. In total, 13 patients (dTGA: n = 8, ccTGA: n = 5) with a median age of 30.3 years were enrolled. LV ECV was higher in patients than in controls [34% (30%-41%) vs. 26% (23%-27%), p < 0.001], with values increased above the upper limit of normal in 10/13 patients (77%). RV ECV tended to be higher in patients than in controls, albeit without statistical significance [29% (27%-32%) vs. 28% (26%-29%), p = 0.316]. Patients with elevated LV ECV had lower LV ejection fraction than those with normal ECV (52 ± 5% vs. 65 ± 4%, p = 0.007). Correlations with clinical parameters were not observed. LV ECV was significantly higher than RV ECV (p = 0.016) in the patient group. In this study, LV ECV was significantly increased in TGA patients compared to controls, and was associated with LV dysfunction. Our data suggest that ECV may serve as a non-invasive tissue marker of heart failure in TGA with systemic RV. Further research is necessary to evaluate the prognostic implications and the potential role of ECV in monitoring disease progression and guiding therapy, aiming to maintain LV function or train the LV for subaortic location in TGA patients from infancy to adulthood.

Strain-dependent stress relaxation behavior of healthy right ventricular free wall

The increasing evidence of stress-strain hysteresis in large animal or human myocardium calls for extensive characterizations of the passive viscoelastic behavior of the myocardium. Several recent studies have investigated and modeled the viscoelasticity of the left ventricle while the right ventricle (RV) viscoelasticity remains poorly understood. Our goal was to characterize the biaxial viscoelastic behavior of RV free wall (RVFW) using two modeling approaches. We applied both quasi-linear viscoelastic (QLV) and nonlinear viscoelastic (NLV) theories to experimental stress relaxation data from healthy adult ovine. A three-term Prony series relaxation function combined with an Ogden strain energy density function was used in the QLV modeling, while a power-law formulation was adopted in the NLV approach. The ovine RVFW exhibited an anisotropic and strain-dependent viscoelastic behavior relative to anatomical coordinates, and the NLV model showed a higher capacity in predicting strain-dependent stress relaxation than the QLV model. From the QLV fitting, the relaxation term associated with the largest time constant played the dominant role in the overall relaxation behavior at most strains from early to late diastole, whereas the term associated with the smallest time constant was pronounced only at low strains at early diastole. From the NLV fitting, the parameters showed a nonlinear dependence on the strain. Overall, our study characterized the anisotropic, nonlinear viscoelasticity to capture the elastic and viscous resistances of the RVFW during diastole. These findings deepen our understanding of RV myocardium dynamic mechanical properties. Statement of significanceAlthough significant progress has been made to understand the passive elastic behavior of the right ventricle free wall (RVFW), its viscoelastic behavior remains poorly understood. In this study, we originally applied both quasi-linear viscoelastic (QLV) and nonlinear viscoelastic (NLV) models to published experimental data from healthy ovine RVFW. Our results revealed an anisotropic and strain-dependent viscoelastic behavior of the RVFW. The parameters from the NLV fitting showed nonlinear relationships with the strain, and the NLV model showed a higher capacity in predicting strain-dependent stress relaxation than the QLV model. These findings characterize the anisotropic, nonlinear viscoelasticity of RVFW to fully capture the total (elastic and viscous) resistance that is critical to diastolic function.

Proteomic and Metabolomic Analyses of Right Ventricular Failure due to Pulmonary Arterial Hypertension.

Right ventricular failure (RVF) is the independent and strongest predictor of mortality in pulmonary arterial hypertension (PAH), but, at present, there are no preventive and therapeutic strategies directly targeting the failing right ventricle (RV). The underlying mechanism of RV hypertrophy (RVH) and dysfunction needs to be explored in depth. In this study, we used myocardial proteomics combined with metabolomics to elucidate potential pathophysiological changes of RV remodeling in a monocrotaline (MCT)-induced PAH rat model. The proteins and metabolites extracted from the RV myocardium were identified using label-free liquid chromatography–tandem mass spectrometry (LC-MS/MS). The bioinformatic analysis indicated that elevated intracellular Ca2+ concentrations and inflammation may contribute to myocardial proliferation and contraction, which may be beneficial for maintaining the compensated state of the RV. In the RVF stage, ferroptosis, mitochondrial metabolic shift, and insulin resistance are significantly involved. Dysregulated iron homeostasis, glutathione metabolism, and lipid peroxidation related to ferroptosis may contribute to RV decompensation. In conclusion, we depicted a proteomic and metabolomic profile of the RV myocardium during the progression of MCT-induced PAH, and also provided the insights for potential therapeutic targets facilitating the retardation or reversal of RV dysfunction in PAH.

Right ventricular involvement in left ventricular non-compaction cardiomyopathy.

BackgroundLeft ventricular non-compaction cardiomyopathy (LVNC) features extensive trabeculations. Involvement of the right ventricle (RV) has been reported; however, distinction from normal RV trabeculation is difficult. This study aimed at assessing RV morphology and function in LVNC by cardiac magnetic resonance (CMR) and transthoracic echocardiography (TTE).MethodsDimensional and functional parameters were assessed according to guidelines. Novel CMR parameters were RV end-diastolic (ED) trabeculated area, RV ED trabeculated volume, and RV ED non-compacted to compacted (NC/N) ratio in short axis (SAX) as well as in four-chamber view (4CH).ResultsTwenty patients with LVNC and 20 controls were included. RV size and function were comparable in LVNC and controls and exhibited a good correlation between TTE and CMR. Although RV trabeculated area, RV trabeculated volume, and RV ED NC/C ratio in SAX as well as in 4CH were larger in LVNC, there was a major overlap with values in controls. RV ED NC/C ratio in SAX correlated with LV ED NC/C ratio (not in 4CH). Quantitative assessment of RV non-compaction was not feasible in TTE.ConclusionsRight ventricle size and function in LVNC can be measured by CMR and TTE, while RV trabeculation can only be quantified by CMR. RV myocardium displays more trabeculations in LVNC; however, overlap with normal individuals is extensive, not allowing separation of patients with LVNC from controls.

Fast high-resolution late gadolinium enhancement magnetic resonance imaging for an accurate detection of myocardial radiofrequency catheter ablation lesions

Abstract Funding Acknowledgements Type of funding sources: None. Background Whole- heart high-resolution free-breathing late gadolinium enhancement (HR-LGE) is a key sequence for detecting radiofrequency catheter ablation (RFCA) lesions. However, long acquisition time is the main limitation especially for dyspneic and claustrophobic patients. Purpose We aimed to introduce an accelerated HR-LGE technique for the detection of myocardial RFCA lesions. Method An under sampled (3-fold) navigator-gated whole- heart HR-LGE (acquired resolution of 1.25 mm3) sequence combined with advanced patch-based low-rank reconstruction was implemented on a 1.5 CMR scanner. Three sheep prospectively underwent radiofrequency ablation at multiple endocardial and epicardial sites. The animals were imaged 3 months later using conventional post-contrast LGE (PSIR, voxel size 1.8x1.4x6mm) and the proposed sequence. A reader graded image quality and diagnostic value of both LGE imaging. Results The acceleration allowed for acquisition times of 3 min 22s ± 20 s at 1.25 mm resolution. Compared with 2D PSIR, HR-LGE showed comparable image quality (P= 0.03). All LGE- positive segments on 2D PSIR in LV myocardium were also detected on HR-LGE (6 segments). Two additional enhanced segments were only visible on HR-LGE (8 segments). LGE-positive segments in RV myocardium were detected on HR-LGE (4 segments) while 2D PSIR was either definitely negative (2 segments) or uncertain (2 segments). Conclusion Accelerated whole-heart HR- LGE allows an accurate detection of left and right myocardial RFCA lesions.

Ventricular tachycardia in Arrhythmogenic Right Ventricular Cardiomyopathy: How to Manage?

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is a condition characterized by fibrofatty replacement of the RV myocardium due to genetic abnormality. Structural changes may be absent or minor in the early stages of the disease and be localized in a specific region of the RV. Clinically it appears as RV electrical instability. To reduce the risk of arrhythmic events or sudden cardiac death, device therapy and pharmacotherapy may be recommended. In this paper, we describe a case of a female with ARVC and a brief discussion based on a literature review. The patient presented with chest discomfort accompanied by palpitation. An electrocardiogram (ECG) showed ventricular tachycardia of RV apex origin, and convert to symmetric inverted T-waves and probable epsilon waves in the right precordial leads, mimicking a pseudo-right bundle branch block (RBBB) pattern following electrical cardioversion. The parasternal short-axis view of echocardiography shows severe right ventricular dilatation. Subsequent workup using CMR was planned but the patient refused. We diagnosed this patient with ventricular tachycardia on a background of suspicious arrhythmogenic right ventricular cardiomyopathy. We were able to provide accurate diagnosis and treatment, avoiding potentially fatal consequences. As a result, it is critical to recognize potential ARVC ECG findings and to know when to pursue further research and implement therapies.

PO-702-02 X-LINKED ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY DUE TO PATHOGENIC EMERIN MUTATION

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic cardiomyopathy characterized by fibrofatty tissue replacement of RV myocardium. The majority of ARVC cases are attributed to mutations in genes coding desmosomal proteins. Rarer cases of ARVC are associated with mutations in nuclear envelope proteins, mainly LMNA and TMEM43. An ARVC phenotype has not been associated with an emerin (EMD) mutation.

Age- and sex-specific characteristics of right ventricular compacted and trabeculated myocardium by cardiac magnetic resonance

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministry for Innovation and Technology in Hungary within the framework of the Therapeutic Development and Bioimaging Programs of Semmelweis University. National Research, Development and Innovation Fund of Hungary, financed under the NVKP_16 funding scheme. The sex-specific characteristics of right ventricular compacted (RV-CM) and RV-trabeculated myocardial mass (RV-TM) over time and the determinants of RV myocardium are less well studied; however, in different conditions, these might provide additional information to the diagnosis. We aimed to describe the age- and sex-specific characteristics of RV-CMi, RV-TMi, and RV volumetric and functional parameters and investigate the determinants of RV myocardial mass with CMR. Two hundred healthy Caucasian volunteers free of known cardiovascular or systemic diseases were enrolled in this study. Four different age groups were established with equal numbers of males and females: Group A (n = 50, 20-29 years, mean age: 24.3 ± 3.2 years), Group B (n = 50, 30-39 years, mean age: 33.6 ± 2.6 years), Group C (n = 50, 40-49 years, mean age: 44.7 ± 2.7 years), and Group D (n = 50, ≥ 50 years, mean age: 55.1 ± 3.9 years). RV volumetric and functional, RV-CMi and RV-TMi values were measured with a threshold-based postprocessing method for CMR. The volumetric parameters, RV-CMi, and RV-TMi were larger in males, and the ejection fraction (EF) was higher in females. The RV-CMi did not correlate with age in either of the sexes, while the RV-TMi decreased with age in females but remained stable in males. The RV-TMi and RV-CMi correlated positively with RV volumetric parameters, the left ventricular (LV)-CMi, the LV-TMi, and each other in both sexes. LV-TMi, LV-CMi, RV end-systolic volume, and sex were independent predictors of RV-TMi. Understanding the natural history of RV-trabeculated and RV-compacted myocardium might have additive value in diagnosing different conditions with RV hypertrophy or hypertrabeculation.

Age- and Sex-Specific Characteristics of Right Ventricular Compacted and Non-compacted Myocardium by Cardiac Magnetic Resonance.

The age and sex-specific characteristics of right ventricular compacted (RV-CMi) and RV-trabeculated myocardial mass (RV-TMi) and the determinants of RV myocardium are less well-studied; however, in different conditions, these might provide additional diagnostic information. We aimed to describe the age- and sex-specific characteristics of RV-CMi, RV-TMi, and RV volumetric and functional parameters and investigate the determinants of RV myocardial mass with cardiac magnetic resonance (CMR). Two hundred healthy Caucasian volunteers free of known cardiovascular or systemic diseases were prospectively enrolled in this study. Four different age groups were established with equal numbers of males and females: Group A (n = 50, 20-29 years, mean age: 24.3 ± 3.2 years), Group B (n = 50, 30-39 years, mean age: 33.6 ± 2.6 years), Group C (n = 50, 40-49 years, mean age: 44.7 ± 2.7 years), and Group D (n = 50, ≥50 years, mean age: 55.1 ± 3.9 years). Left ventricular (LV) and RV volumetric, functional, CMi, and TMi values were measured with a threshold-based post-processing CMR method. The volumetric parameters, RV-CMi, and RV-TMi values were larger, and the ejection fraction (EF) was lower in males. The RV-CMi did not correlate with age in either of the sexes, while the RV-TMi decreased with age in females but remained stable in males. The RV-TMi and RV-CMi correlated positively with RV volumetric parameters, the LV-CMi, the LV-TMi, and each other in both sexes. LV-TMi, LV-CMi, RV end-systolic volume, and sex were independent predictors of RV-TMi. Understanding the characteristics of RV-trabeculated and RV-compacted myocardium might have additive value in diagnosing different conditions with RV hypertrophy or hypertrabeculation.

Role of oxidative stress versus lipids in monocrotaline-induced pulmonary hypertension and right heart failure.

Pulmonary hypertension (PH) is a global health issue with a prevalence of 10% in ages >65 years. Right heart failure (RHF) is the main cause of death in PH. We have previously shown that monocrotaline (MCT)‐induced PH and RHF are due to an increase in oxidative stress. In this study, probucol (PROB), a strong antioxidant with a lipid‐lowering property, versus lovastatin (LOV), a strong lipid‐lowering drug with some antioxidant effects, were evaluated for their effects on the MCT‐induced RHF. Rats were treated (I.P.) with PROB (10 mg/kg ×12) or LOV (4 mg/kg ×12), daily 6 days before and 6 days after a single MCT injection (60 mg/kg). Serial echocardiography was performed and at 4‐week post‐MCT, lung wet‐to‐dry weight, hemodynamics, RV glutathione peroxidase (GSHPx), superoxide dismutase (SOD), catalase, lipid peroxidation, and myocardial as well as plasma lipids were examined. MCT increased RV systolic and diastolic pressures, wall thickness, RV end diastolic diameter, mortality, and decreased ejection fraction as well as pulmonary artery acceleration time. These changes were mitigated by PROB while LOV had no effect. Furthermore, PROB prevented lipid peroxidation, lowered lipids, and increased GSHPx and SOD in RV myocardium. LOV did decrease the lipids but had no effect on antioxidants and lipid peroxidation. A reduction in oxidative stress and not the lipid‐lowering effect of PROB may explain the prevention of MCT‐induced PH, RHF, and mortality. Thus targeting of oxidative stress as an adjuvant therapy is suggested.

Long Term Follow-Up in a Patient with Arrhythmogenic Right Ventricular Dysplasia

Abstract This case report describes eight years of follow-up in a young adult with arrhythmogenic right ventricular dysplasia (ARVD). He presented with exertional palpitations, symmetric T wave inversions and possible epsilon waves in the right precordial leads on electrocardiogram (EKG), raising suspicion for ARVD. Transthoracic echocardiography revealed a dilated and excessively trabeculated right ventricle (RV), and cardiac magnetic resonance imaging showed fatty infiltration of the RV myocardium. These findings established the diagnosis of ARVD, and given his palpitations, a defibrillator was implanted. Over the next years, he had several episodes of ventricular tachycardia requiring therapy from his device, despite escalating medical therapy. He therefore underwent radiofrequency catheter ablation for the VT, which successfully controlled the VT.

Efficacy of shear wave elastography for evaluating right ventricular myocardial fibrosis in monocrotaline-induced pulmonary hypertension rats

BackgroundRight ventricular (RV) function is important for outcomes in pulmonary hypertension. Evaluation of RV myocardial characteristics is useful to assess the disease severity. Shear wave elastography (SWE) provides information of shear wave (SW) elasticity, which is related to tissue hardness, and SW dispersion slope, which reflects tissue viscosity. This study aimed to test the hypothesis that SW elasticity is increased and SW dispersion slope is decreased in the right ventricle of monocrotaline (MCT)-induced pulmonary hypertension rats. MethodsRats were divided into MCT-induced pulmonary hypertension group (n = 10) and control group (n = 10). SW elasticity and SW dispersion slope were measured on excised hearts. Myocardial fibrosis was evaluated histologically. ResultsRV hypertrophy was observed in the MCT group. SW elasticity of right ventricle was higher in the MCT group than in the control group (3.5 ± 0.9 kPa vs. 2.5 ± 0.4 kPa, p < 0.01). SW dispersion slope of right ventricle was lower in the MCT group than in the control group (5.3 ± 1.7 m/s/kHz vs. 7.7 ± 1.5 m/s/kHz, p < 0.01). The fibrosis area of right ventricle was increased in MCT group compared with control group (18 ± 5% vs. 8 ± 3%, p < 0.01), and was positively related to SW elasticity and negatively related to SW dispersion slope. ConclusionsHigher SW elasticity and lower SW dispersion slope were observed in the fibrotic myocardium of right ventricle in MCT-induced pulmonary hypertension rats. SWE may have the potential to evaluate RV function by assessing myocardial characteristics.

From Safety to Benefit in Cell Delivery During Surgical Repair of Ebstein Anomaly: Initial Results

BackgroundThe objective of this study is to assess the safety and early impact of intramyocardial delivery of autologous bone marrow–derived mononuclear cells (BM-MNC) at time of surgical Ebstein repair. MethodsPatients with Ebstein anomaly (ages 6 months to 30 years) scheduled to undergo repair of the tricuspid valve were eligible to participate in this open-label, non-randomized phase I clinical trial. BM-MNC target dose was 1-3 million cells/kg. Ten patients have undergone surgical intervention and cell delivery to the right ventricle (RV) and completed 6-month follow-up. ResultsAll patients underwent surgical tricuspid valve repair and uneventful BM-MNC delivery; there were no ventricular arrhythmias and no adverse events related to study product or delivery. Echocardiographic RV myocardial performance index improved and RV fractional area change showed an initial decline and then through study follow-up. There was no evidence of delayed myocardial enhancement or regional wall motion abnormalities at injection sites on 6-month follow-up magnetic resonance imaging. ConclusionsIntramyocardial delivery of BM-MNC after surgical repair in Ebstein anomaly can be performed safely. Echocardiography variables suggest a positive impact of cell delivery on the RV myocardium with improvements in both RV size and wall motion over time. Additional follow-up and comparison to control groups are required to better characterize the impact of cell therapy on the myopathic RV in Ebstein anomaly.

Cardiopulmonary hemodynamics and respiratory function in patients with chronic obstructive pulmonary disease according to doppler echocardiography data

Aim . Determination of the functional state of cardiopulmonary hemodynamics in patients with chronic obstructive pulmonary disease (COPD) with varying severity of bronchial obstruction and respiratory failure using echodopplercardiography. Materials and methods . In 82 patients with COPD, the functional state of cardiopulmonary hemodynamics was evaluated using ultrasound methods. All subjects were divided into 2 groups depending on the severity of COPD (moderate and severe course). Results . It was found that in patients with COPD, impaired diastolic function of the right ventricle (RV) may be preclinical. Thus, in patients with COPD stage 2, compared with control in the P-mode and tissue Doppler sonography (TDI), mild changes in the diastolic function (impaired relaxation) of the RV myocardium were revealed (E/A 0.70±0.13 and 1.56±0.18, E/Em 8.45±0.15 and 6.89±0.19, respectively). In patients with COPD stage 3, the mean values of these RV parameters significantly differed (E/A 0.69±0.04 and E/Em 9.34±0.18) and corresponded to moderately expressed diastolic dysfunction. Conclusions . In severe COPD in stage 3, significant violations of the structure and function of the RV were determined. The compensatory capabilities of both cardiac ventricles were depleted, the interventricular interaction changed, which created the conditions for the progression of heart failure and the development of chronic cor pulmonale.