Improvement In Right Ventricular Function Research Articles

Abstract 13594: Adverse Right Ventricular Remodelling, Function and Stress Responses in Obesity: Implications for Severe Acute Respiratory Illness

Introduction: The mechanisms linking obesity to increased mortality in patients with coronavirus-disease 2019 (COVID-19) are unclear. Hypothesis: We hypothesised that obesity would be associated with adverse right ventricular (RV) remodelling and function which might be further exacerbated by COVID-19 associated increases in RV afterload/demand. Methods: We used echocardiography and computed tomography to establish links between RV dimensions and function and bodyweight in patients with severe COVID-19. In obese and non-obese participants without COVID-19, we used cardiovascular magnetic resonance to define the effects of obesity upon RV volumes, energetics, systolic function and stress reserve. Results: In patients with severe COVID-19, increasing bodyweight was associated with disproportionate RV dilatation (n=26, echocardiography, R=0.42, P=0.03, CT n=34, R=0.23, P=0.004) and impairment of RV systolic function (fractional area change (FAC) R=-0.45, P=0.04); obesity (BMI >30kg/m2) was associated with a 32% reduction in RV FAC (P=0.03). Similar associations were seen in a validation cohort (n=91, all P<0.05). In participants without COVID-19, class III obesity (n=54, BMI 47±4 kg/m 2 ) was associated with RV remodelling, impaired cardiac energetics (PCr/ATP ratio 23% lower, P<0.001) and reduction in RV systolic function at rest (by 3±1%, P=0.01), which was related to reduced energetics (R=0.3, P=0.04). Participants with class I-II obesity (BMI 35±5 kg/m 2 , n=27) had impaired RV diastolic filling rate at rest (P<0.001) and blunted RV dobutamine stress systolic response (by 68%, P=0.03) and diastolic response (by 78%, P=0.008). Surgical weight loss in patients obesity (n=37, 34±15kg weight loss) was associated with improvement in RV volume (12±26 ml lower, P=0.006) and function (ejection fraction 2±5% higher, P=0.03). Conclusions: Increasing body weight is associated with both significant alterations in RV volumes, systolic function and stress responses which are mitigated with weight loss and also with disproportionate RV dilatation and dysfunction in severe COVID-19. RV dysfunction is a modifiable mechanism which might link obesity to adverse outcomes in patients with COVID-19 and other disorders stressing the right heart.

S62798, a TAFIa inhibitor, accelerates endogenous thrombolysis in a murine model of pulmonary thromboembolism

Abstract Pulmonary embolism (PE) is the third leading cause of cardiovascular death in western countries. The enhancement of fibrinolysis constitutes a promising approach to treat thrombotic diseases. In patients, venous thrombosis and thromboembolism risks are associated with increased plasma levels of TAFI (Thrombin Activatable Fibrinolysis Inhibitor) antigen as well as the active form TAFIa. S62798 is a competitive, selective and potent human TAFIa inhibitor (IC50±SD=11.2±0.4nM). It is however less potent on mouse TAFIa (IC50±SD=270±39nM). Here, we tested the ability of S62798 to enhance endogenous fibrinolysis in a mouse model of pulmonary thromboembolism. Human Tissue Factor (TF) was injected in C57Bl6 male mice. Ten minutes later, mice (n=4 to 14 per group) were treated (IV) with S62798 (from 0.01 to 100mg/kg) or vehicle (0.9% NaCl). Ten or twenty minutes (min) later, mice were anesthetized and lungs were collected, homogenized and pulmonary fibrin was quantified by ELISA. Results are expressed as ratio of geometric mean of pulmonary fibrin (μg/mL): tested treatment/ vehicle [95% confidence interval (CI)]. Ten minutes after S62798 treatment, pulmonary fibrin deposition was dose-dependently decreased with a Minimal Effective Dose of 0.04mg/kg [90% prediction interval 0.037 - 0.051] and an ED50 of 0.03mg/kg [95% CI: 0.01; 0.06]. Mice were then treated with 0.1mg/kg S62798 or vehicle (10 min after TF induction) and fibrin deposition in lungs was quantified 10 and 20 minutes post S62798 treatment. The level of pulmonary fibrin deposition was significantly decreased (p<0.0001) compared to vehicle group (ratio 0.31 [0.21; 0.45] at 10 min; 0.35 [0.24; 0.51] at 20 min). Finally, the effect of S62798 (1mg/kg) in combination with heparin was evaluated (n=10/group). When administered 10 min before TF injection, heparin (2000IU/kg) significantly (p<0.0001) decreased pulmonary fibrin level (20 min post TF: ratio 0.03 [0.01; 0.05]). When treatment was done in a curative setting (10 min post TF), heparin alone had no effect (p=0.85) on fibrin deposition (ratio 0.96 [0.65; 1.43]) whereas a similar significant (p<0.0001) decreased pulmonary fibrin deposition was observed in response to S62798 alone or associated with heparin (ratio 0.27 [0.18; 0.40] (S62798 alone) and 0.29 [0.20; 0.43] (S62798+heparin)). In this model, curative S62798 treatment, alone or associated to heparin, accelerated clot degradation by potentiating endogenous fibrinolysis and thus decreased pulmonary fibrin deposition. Due to its capacity to enhance endogenous fibrinolysis, S62798, which has completed phase I studies, is expected to be a therapeutic option for intermediate high risk PE patients on top of anticoagulants. With early recanalization, S62798 should rapidly reduce pulmonary artery pressure and resistance, with concomitant improvement in right ventricular function, preserving cardiac function, and reducing acute PE-related morbidity and mortality in these patients. Funding Acknowledgement Type of funding source: None

Ranolazine Improves Right Ventricular Function in Patients With Precapillary Pulmonary Hypertension: Results From a Double-Blind, Randomized, Placebo-Controlled Trial

IntroductionA major outcome determinant in patients with precapillary pulmonary hypertension (PH) is right ventricular (RV) function. We studied the effect of ranolazine on RV function over 6 months using cardiovascular magnetic resonance (CMR) imaging in patients with precapillary PH (groups I, III, and IV). Methods and ResultsWe enrolled patients with PH and RV dysfunction (CMR imaging ejection fraction [EF] of <45%) in a longitudinal, randomized, double-blinded, placebo controlled, multicenter study of ranolazine treatment. All enrolled patients were on stable PH-specific therapy. Enrolled patients were assessed using CMR imaging, New York Heart Association functional class, N-terminal pro brain natriuretic peptide, 6-minute walk test, and quality of life health outcomes at baseline and repeated at the end of treatment. The primary outcome was change in RVEF after 6 months of treatment. Analysis of covariance was used to analyze the longitudinal changes taking into account baseline values, age, and sex, based on per protocol population. Twenty-two patients were enrolled, and 9 patients completed follow-up CMR imaging after ranolazine treatment and 6 completed placebo treatment. There was significant increase in RVEF at end of treatment compared with baseline in the ranolazine group adjusted for baseline values, age, and sex. There were no statistically significant changes in secondary outcomes such as changes in New York Heart Association functional class, 6-minute walk distance, N-terminal pro brain natriuretic peptide, or quality of life measures. Ranolazine treated patients experienced a higher number of adverse events, but only one was discontinued owing to side effects. ConclusionsRanolazine may improve RV function in patients with precapillary PH. Larger studies are needed to confirm the beneficial effects of ranolazine.

Systematic Review: Does Balloon Pulmonary Angioplasty (BPA) Improve Right Ventricular Function in CTEPH Patients? Evaluation Based on Imaging Findings

Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening disease with many complications, such as right heart failure. Therefore, a direct and efficient therapy is imperative. This review aims to determine the effectiveness of balloon pulmonary angioplasty (BPA) on right ventricular (RV) function among CTEPH patients, using imaging methods. From April 2019 to August 2019, PubMed database was searched for randomized control trials and cohort studies conducted until August 2019, evaluating the impact of BPA on RV function as assessed by non-invasive modalities. Data were extracted, and validity was assessed by 2 reviewers and graded using the Cochrane Collaboration tool for assessing a risk of bias. A total of 204 articles were screened for relevance. Only 14 articles were deemed eligible for this review, 4 studies being prospective and 10 retrospective trials. Totally 395 patients with CTEPH who underwent BPA enrolled. The findings indicated improvement in hemodynamic parameters and RV function. BPA is an effective and appropriate therapy for non-operable CTEPH patients leading to significant improvements in RV function. Two-dimensional and 3D echocardiography and cardiac magnetic resonance imaging (CMRI) are reliable non-invasive imaging methods for RV function assessment after BPA.

Right ventricular reserve post mitral valve repair is associated with heart failure hospitalization.

Right ventricular impairment is a predictor of cardiovascular outcomes in patients with degenerative mitral regurgitation. However, the time course of right ventricular functional changes post-surgical mitral valve repair remains largely unknown. Herein, using right ventricular-focused echocardiography, we aimed to investigate right ventricular reserve and its impact on hospitalization for heart failure after mitral valve repair. In this prospective study, we enrolled 108 patients scheduled to undergo surgical repair of degenerative mitral regurgitation. Echocardiography, including right ventricular strain analysis, was performed prior to, and one month and six months post mitral valve repair. Right ventricular strain that improved one month post-surgery was defined as reserved right ventricular. In addition, any cardiovascular outcomes comprising heart failure that required admission were recorded. The median follow-up duration is 31 months. Despite a significant improvement in mitral valve regurgitant volume post-operatively, left ventricular ejection fraction (LVEF) at six months was similar to LVEF at baseline. There was a transient decrease in LV longitudinal strain at one month that was recovered six months post mitral valve repair. Regarding the right ventricular, in contrast with conventional right ventricular parameters, including right ventricular tissue Doppler S', fractional area change and tricuspid annular plane systolic excursion (TAPSE), only resolution of right ventricular strain at one month predicted the subsequent myocardial recovery. Furthermore, patients with reserved right ventricular had a lower risk of hospitalization for heart failure compared to those with non-reserved right ventricular. Collectively, the early resolution of right ventricular strain is associated with the improvement in right ventricular function (measured by TAPSE) and in heart failure hospitalization in patients who had undergone surgical mitral valve repair for degenerative mitral regurgitation.

First-in-Human Transcatheter Tricuspid Valve Repair: 30-Day Follow-Up Experience With the Mistral Device

ObjectivesThis study sought to report short-term results of safety, performance, and efficacy of the Mistral device first-in-human study in patients suffering from severe functional tricuspid insufficiency. BackgroundPatients who suffer from severe tricuspid regurgitation (TR) and who are at high surgical risk have no standard care therapy. Therefore, minimally invasive and safer methods are sought. The Mistral device is an investigational spiral-shaped device intended for percutaneous transcatheter repair. The Mistral device approximates the tricuspid leaflets by grasping together the chordae tendineae of the tricuspid valve. MethodsSeven patients (4 women; mean age 73.14 ± 7.4 years) with severe (n = 5) and massive (n = 2) symptomatic TR and high surgical risk underwent Mistral tricuspid repair under transesophageal echocardiography guidance. ResultsMistral was successfully implanted in all cases with a single device deployed in 6 patients, with 2 devices deployed in 1 patient. No procedural or 30-day adverse events occurred. TR was reduced by at least 1 grade in all patients. Effective regurgitant orifice area was reduced from median 0.52 cm2 (interquartile range [IQR]: 0.40 to 0.60 cm2) at baseline to 0.15 cm2 (IQR: 0.14 to 0.21 cm2) at 30 days post-procedure (p < 0.01), vena contracta width was reduced from 0.95 cm (IQR: 0.81 to 1.16 cm) to 0.62 cm (IQR: 0.52 to 0.67 cm) (p < 0.05), and regurgitant volume decreased from 49.4 ml/beat (IQR: 45.2 to 57.7 ml/beat) to 19.7 ml/beat (IQR: 12.4 to 23.9 ml/beat) (p < 0.01). Right ventricular fractional area change improved from 27.0% (IQR: 21.3% to 33.5%) at baseline to 38.5% (IQR: 29.0% to 47.1%) at 30-day follow-up (p < 0.05). Significant improvements in New York Heart Association functional class, Kansas City Cardiomyopathy Questionnaire score, and 6-min walk test were observed at 30 days. ConclusionsTricuspid valve repair with the Mistral device appears safe and leads to 30-day reduction of tricuspid insufficiency and improvement of right ventricular function and exercise capacity.

Unloading using Impella CP during profound cardiogenic shock caused by left ventricular failure in a large animal model: impact on the right ventricle

Background and aimThis study aimed to assess right ventricular (RV) function during cardiogenic shock due to acute left ventricular (LV) failure, including during LV unloading with Impella CP and an added moderate dose of norepinephrine.MethodsCardiogenic shock was induced by injecting microspheres in the left main coronary artery in 18 adult Danish Landrace pigs. Conductance catheters were placed in both ventricles and pressure-volume loops were recorded simultaneously.ResultsCardiogenic shock due to LV failure also impaired RV performance, which was partially restored during haemodynamic support with Impella CP, as demonstrated by changes in the ventriculo-arterial coupling (Ea/Ees ratio) (baseline (median [Q1;Q3]) 1.2 [1.1;1.6]), cardiogenic shock (3.0 [2.4;4.5]), Impella CP (2.1 [1.3;2.7]) (pBaseline vs CS < 0.0001, pCS vs Impella = 0.001)). Impella CP support also improved RV stroke work (SW) (cardiogenic shock 333 [263;530] vs Impella CP (830 [717;1121]) (p < 0.001). Moderate norepinephrine infusion concomitant with Impella CP further improved RV SW (Impella CP (818 [751;1065]) vs Impella CP+moderate norepinephrine (1231 [1142;1335]) (p = 0.01)) but at the expense of an increase in LV SW (Impella CP (858 [555;1392]) vs Impella CP+moderate norepinephrine (2101 [1024;2613]) (p = 0.04)).ConclusionsThe Impella CP provided efficient LV unloading, improved RV function, and end-organ perfusion. Moderate doses of norepinephrine during Impella support further improved RV function, but at the expense of an increase in SW of the failing LV.

EkoSonic® endovascular system and other catheter-directed treatment reperfusion strategies for acute pulmonary embolism: overview of efficacy and safety outcomes

ABSTRACT Introduction Studies performed in the past decade suggested that evolving reperfusion strategies may improve early outcomes of patients with acute pulmonary embolism (PE) and hemodynamic decompensation. In this regard, catheter-directed treatment (CDT) options are receiving increasing attention. Areas covered A broad spectrum of CDT options exists for the treatment of patients with acute PE. Procedures include catheter-directed local thrombolysis with or without ultrasound assistance, catheter-directed mechanical or suction embolectomy, and combined pharmaco-mechanical approaches. We present here an overview of the available CDT techniques, focusing on the EkoSonic® endovascular system. Expert commentary CDT, particularly local ultrasound accelerated thrombolysis, continues to evolve. Its increasing popularity is the result of accumulating promising results, which suggest a relief of right ventricular (RV) pressure overload and improvement of RV function. These favorable effects on surrogate endpoints were accompanied by a low rate of procedure-related adverse events, notably intracranial hemorrhage. Although the overall risk of serious bleeding appears to be low in CDT, the lack of direct comparisons with other reperfusion options does not allow definitive conclusions. Prospective controlled trials with robust clinical outcomes are urgently needed to establish the postulated benefits of CDT in selected patients with acute PE.

Speckle tracking for predicting outcomes of balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension.

Right ventricular (RV) function is a prognostic marker of chronic thromboembolic pulmonary hypertension (CTEPH). We used two-dimensional (2D) speckle-tracking echocardiography (STE) to evaluate the therapeutic effects of balloon pulmonary angioplasty (BPA) in CTEPH patients. A total of 46 CTEPH patients who underwent 2D STE before and after BPA were enrolled in this retrospective study. The following RV functional parameters were measured: tricuspid annular plane systolic excursion (TAPSE), right ventricular fractional area change (RVFAC), RV index of myocardial performance (RIMP), and free wall longitudinal strain (RVFWLS). Satisfactory BPA was defined as mean pulmonary arterial pressure (mPAP) <25mmHg or improvement in mPAP>10mmHg after BPA. Patients were divided into two groups according to mPAP values: group I had satisfactory BPA outcomes; group Ⅱ had unsatisfactory BPA outcomes. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to determine the optimal cutoff values and the ability of RVFWLS to predict successful BPA outcomes. After BPA, SPAP measured by echocardiography (SPAPecho ) and RIMP decreased, but TAPSE, RVFAC, and RVFWLS increased. Before BPA, group Ⅰ had significantly better RV function than group Ⅱ. Multifactor logistic regression analysis identified RVFWLS as an independent factor associated with satisfactory BPA outcomes. The optimal cutoff value for RVFWLS in predicting satisfactory BPA outcomes was -12.2%. Balloon pulmonary angioplasty improves RV function in CTEPH patients. RVFWLS is a valuable noninvasive tool with which to assess the treatment effects of BPA. CTEPH patients with lower RVFWLS may have limited benefit from BPA.

Echocardiographic assessment in patients with atrial fibrillation (AF) and normal systolic left ventricular function before and after catheter ablation: If AF begets AF, does pulmonary vein isolation terminate the vicious circle?

Radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) can be curative. There are conflicting data on whether AF associated atrial and ventricular structural remodeling reverses after ablation. The aim of this study was to evaluate the hemodynamic effect of AF ablation in patients with preserved left ventricular ejection fraction (LVEF). Forty three AF patients were studied (aged 56 ± 11 years; 29 male, 23% persistent AF, LVEF ≥ 50%) in whom RFCA was performed. Echocardiographic evaluation of atrial and ventricular diameters, volumes and strain imaging by two-dimensional speckle tracking were performed before and at least 6 months after RFCA. Nine patients had AF during baseline examination. A significant decrease in the left (LA) and right (RA) atrial volume and an increase in the LA strain were observed 15 ± 7 months after RFCA. In the subgroup with baseline sinus rhythm, the increment in LA strain was only borderline significant. An increase in RA, right ventricular (RV) and Biatrial strain was noticed (p < 0.05). LVEF and global longitudinal strain of the left ventricle (LV), however, did not improve substantially. Radiofrequency catheter ablation of AF in patients with preserved LV systolic function results in significant improvement in RA and RV function with a substantial reduction in LA and RA size. No deleterious impact of AF ablation on LA function was revealed.

Supra-coronary aortic banding improves right ventricular function in experimental pulmonary arterial hypertension in rats by increasing systolic right coronary artery perfusion.

Pulmonary arterial hypertension (PAH) results in right ventricular (RV) dysfunction owing, in part, to RV ischemia. The relative contribution of RV microvascular rarefaction vs reduced right coronary artery perfusion pressure (RCA-PP) to RV ischemia remains unknown. We hypothesize that increasing RCA-PP improves RV function in PAH by increasing RV systolic perfusion. Supra-coronary aortic banding (SAB) or sham surgery was performed on male Sprague-Dawley rats. Seven to ten days later, rats received either monocrotaline (MCT; 60mg/kg) or saline. After 1month, echocardiography, cardiac catheterization, 99m Tc-sestamibi single-photon emission computed tomography (SPECT) and microsphere infusion studies were performed. The RV was harvested for measurement of hypertrophy (RVH), fibrosis and immunoblotting, and the lung was harvested for pulmonary artery (PA) histology. Supra-coronary aortic banding increased systolic pressures in proximal aorta and systolic RCA-PP in SAB+MCT vs MCT rats (114±12 vs 5±9mmHg), without altering diastolic RCA-PP. SAB+MCT rats had improved RV function vs MCT rats, evident from their significantly increased cardiac output (CO), RV free wall (RVFW) thickening, tricuspid annular plane systolic excursion (TAPSE) and RV-PA coupling indices. RV-PA coupling indices and CO correlated directly with systolic RCA-PP. RV perfusion was increased in SAB+MCT vs MCT rats and correlated well with CO; whereas microvascular rarefaction was unaltered. SAB+MCT rats had less RVH and fibrosis and lower PA pressures vs MCT rats. SAB+MCT rats had significantly lower RV pyruvate kinase muscle isoform 2/1 ratios than MCT rats, consistent with restoration of oxidative metabolism. A SAB-induced increase in systolic RCA-PP improves RV perfusion and function in MCT rats. Maintaining systolic RCA perfusion can preserve RV function in PAH.

A Rare Case of Pericardial Decompression Syndrome in a Filipino Female Patient With Suspected Malignant Pericardial Effusion

Pericardial decompression syndrome (PDS) is a rare, under-reported and potentially fatal complication of pericardial drainage characterized by paradoxical hemodynamic deterioration. The onset ranges from immediate to as long as 48 h post drainage. We present a case of a 51-year-old woman admitted due to progressive dyspnea. She was hemodynamically stable but with signs of cardiac tamponade. On two-dimensional echocardiography (2D-echo) there was a massive pericardial effusion in tamponade physiology. Immediate surgical drainage was done but intra-operatively there was depressed cardiac contractility necessitating inotropic support. Post-operative 2D-echo showed right ventricular (RV) and left ventricular (LV) systolic dysfunction. She was admitted in the intensive care unit (ICU) for 72 h. Repeat 2D-echo showed marked improvement in RV and LV systolic function. She was then discharged improved on the fifth hospital day. The pathophysiology of PDS is still not very clear. The simplest mechanism is that sudden removal of compressing pericardial fluid causes increased venous return with expansion of the RV at the expense of the LV leading to acute heart failure. There are no published studies to propose preventive measures and treatment remains supportive. There has been only one published case reported here in our country. We report this case of a patient who successfully recovered from PDS. J Med Cases. 2020;11(4):86-89 doi: https://doi.org/10.14740/jmc3446

Bisoprolol therapy does not reduce right ventricular sympathetic activity in pulmonary arterial hypertension patients.

Right ventricular (RV) function and autonomic dysfunction are important determinants of morbidity and mortality in patients with pulmonary arterial hypertension (PAH). Although successful in animal studies, effects of beta-blocker therapy on RV function in clinical trials were disappointing. To understand this discrepancy, we studied whether beta-blocker therapy changes RV sympathetic activity. Idiopathic PAH (IPAH) patients received beta-blocker therapy (uptitrated to a maximal tolerated dose) and underwent cardiac magnetic resonance imaging, right heart catheterization, and a [11C]-hydroxyephedrine positron emission tomography ([11C]HED PET) scan at baseline to determine, respectively, RV ejection fraction (RVEF), RV pressures, and sympathetic activity. [11C]HED, a norepinephrine analogue, allows determination of sympathetic innervation of the RV. [11C]HED retention index reflects norepinephrine transporter activity. As a consequence of excessive catecholamine levels in the synaptic cleft, this transporter may be downregulated. Therefore, low [11C]HED retention index indicates high sympathetic activity. 13 IPAH patients underwent [11C]HED PET scans at baseline and after bisoprolol treatment. Although heart rate was reduced, systemic modulation of autonomic activity by bisoprolol did not affect local RV sympathetic nerve activity, RV function, or RV wall tension. In PAH patients, RV [11C]HED retention index was lower compared to LV tracer uptake (p<0.01) and was related to systolic wall tension (R2 = 0.4731, p<0.01) and RV function (R2 = 0.44, p = 0.01). In RV failure, the tolerated dosage of bisoprolol did not result in an improvement of RV function nor in a reduction in RV sympathetic activity.

Right Ventricular Function Correlates with Local Mechanical Dyssynchrony of Interventricular Septum in Patients with Non-Ischemic Dilated Cardiomyopathy

The underlying mechanisms of right ventricular (RV) dysfunction in patients with non-ischemic dilated cardiomyopathy (NICM) remain poorly defined. We evaluated a potential correlation between local mechanical dyssynhcrony of interventricular septum (IVS) and RV function in these patients. We analyzed electromechanical data of 30 NICM patients with NYHA class III, and left ventricular ejection fraction (LVEF) <40% undergoing CD34+ cell therapy. All patients received granulocyte-colony stimulating factor for 5 days; CD34+ cells were collected by apheresis and injected transendocardially. At baseline, and at 6 months after therapy we performed electromechanical mapping and echocardiography. Local mechanical dyssynchrony of IVS was defined as a temporal difference between global and segmental peak systolic displacement normalized to the average duration of the RR interval on electromechanical mapping. Using echocardiography, RV function was assessed by tricuspid annular plane systolic excursion (TAPSE), peak systolic velocity of tricuspid annulus (St), and fractional area change (FAC). RV dysfunction was defined as TAPSE <1.7 cm, St <9.5 cm/s, and FAC< 35%. At baseline, RV function was impaired in 19 patients (63%, Group A), and preserved in 11 patients (37%, Group B). The two groups did not differ in age (54±10 years in Group A vs. 53±9 years in Group B, P=0.62), sex (male: 84% vs. 82%, P=0.87), creatinine (0.86±0.25 mg/dL vs. 0.89±0.31 mg/dL, P=0.60), bilirubin (0.91±0.25 mg/dL vs. 0.82±0.34 mg/dL, P=0.25), LVEF (32.5±9.4% vs. 34.9±8.3%, P=0.29), or NTproBNP levels (1467±1057 pg/mL vs. 1195±1175 pg/mL, P=0.30). On baseline electroanatomical mapping, local mechanical dyssynchrony of IVS was significantly higher in Group A than in Group B (25.7±8.8 % vs. 16.9±9.5 %, P=0.001). In Group A, we found an improvement in RV function at 6 months after cell therapy (TAPSE: +0.33±0.54 cm, P=0.01; St: +1.3±2.1 cm/s; P=0.02; FAC: +9.2±2.3%, P=0.01). In parallel with RV improvement, we observed a significant decrease in IVS dyssynchrony (-10.2±5.2 %). RV function in NICM patients correlates with local mechanical dyssynchrony of IVS. Transendocardial CD34+ cell therapy appears to be associated with decreased IVS dyssynchrony and improved RV function in this patient population.

Epigenetic Metabolic Reprogramming of Right Ventricular Fibroblasts in Pulmonary Arterial Hypertension: A Pyruvate Dehydrogenase Kinase-Dependent Shift in Mitochondrial Metabolism Promotes Right Ventricular Fibrosis.

Right ventricular (RV) fibrosis in pulmonary arterial hypertension contributes to RV failure. While RV fibrosis reflects changes in the function of resident RV fibroblasts (RVfib), these cells are understudied. Examine the role of mitochondrial metabolism of RVfib in RV fibrosis in human and experimental pulmonary arterial hypertension. Male Sprague-Dawley rats received monocrotaline (MCT; 60 mg/kg) or saline. Drinking water containing no supplement or the PDK (pyruvate dehydrogenase kinase) inhibitor dichloroacetate was started 7 days post-MCT. At week 4, treadmill testing, echocardiography, and right heart catheterization were performed. The effects of PDK activation on mitochondrial dynamics and metabolism, RVfib proliferation, and collagen production were studied in RVfib in cell culture. Epigenetic mechanisms for persistence of the profibrotic RVfib phenotype in culture were evaluated. PDK expression was also studied in the RVfib of patients with decompensated RV failure (n=11) versus control (n=7). MCT rats developed pulmonary arterial hypertension, RV fibrosis, and RV failure. MCT-RVfib (but not left ventricular fibroblasts) displayed excess mitochondrial fission and had increased expression of PDK isoforms 1 and 3 that persisted for >5 passages in culture. PDK-mediated decreases in pyruvate dehydrogenase activity and oxygen consumption rate were reversed by dichloroacetate (in RVfib and in vivo) or siRNA targeting PDK 1 and 3 (in RVfib). These interventions restored mitochondrial superoxide and hydrogen peroxide production and inactivated HIF (hypoxia-inducible factor)-1α, which was pathologically activated in normoxic MCT-RVfib. Redox-mediated HIF-1α inactivation also decreased the expression of TGF-β1 (transforming growth factor-beta-1) and CTGF (connective tissue growth factor), reduced fibroblast proliferation, and decreased collagen production. HIF-1α activation in MCT-RVfib reflected increased DNMT (DNA methyltransferase) 1 expression, which was associated with a decrease in its regulatory microRNA, miR-148b-3p. In MCT rats, dichloroacetate, at therapeutic levels in the RV, reduced phospho-pyruvate dehydrogenase expression, RV fibrosis, and hypertrophy and improved RV function. In patients with pulmonary arterial hypertension and RV failure, RVfib had increased PDK1 expression. MCT-RVfib manifest a DNMT1-HIF-1α-PDK-mediated, chamber-specific, metabolic memory that promotes collagen production and RV fibrosis. This epigenetic mitochondrial-metabolic pathway is a potential antifibrotic therapeutic target.

Transcatheter Aortic Valve Replacement in Left Ventricular Assist Device Patients with Aortic Regurgitation

ABSTRACT Backgro und: Development of aortic regurgitation (AR) following left ventricular assist device (LVAD) implantation is common, and it is associated with a poor prognosis. Transcatheter aortic valve replacement (TAVR) has become a mainstay therapy for patients with severe aortic stenosis, with an off-label use for severe AR. The aim of this study was to assess the feasibility and durability of TAVR in LVAD patients with significant AR. Methods: We evaluated all LVAD patients within our database that underwent TAVR for AR. Clinical and echocardiographic data were collected before and after TAVR procedure. Aortic regurgitant fraction (RF) was calculated using outflow graft Doppler echocardiography. Results: Seven patients underwent nine attempted TAVR procedures. Median age was 69 (IQR 63–73) and 43% were female. Median time from LVAD to TAVR was 23 (IQR 17–52) months. One procedure was aborted due to vascular complications, and one patient underwent two separate procedures 22 months apart. Five patients (71%) survived over median follow-up of 9 (IQR 6–23) months. Two patients died of paravalvular complications following device deployment. Procedural success was achieved in 67% of attempts, with significant improvement in RF from 44.8% (IQR 37.6–63.6) pre-procedurally to 28.1% (IQR 0.30–29.6) at six-month follow-up. Qualitatively, mild or moderate paravalvular leak was noted on all surviving patients at one- and six-month follow-up. There was significant improvement in right ventricular function at 6-month follow-up. Conclusion: TAVR is a reasonable option for treating LVAD-induced AR. Longer follow-up and larger cohorts are needed to assess the durability and long-term efficacy of this procedure. Abbreviations: AR: Aortic regurgitation; AV: Aortic valve; LV: Left ventricle; LVAD: Left ventricular assist device; LVIDd: Left ventricular internal dimension at end-diastole; LVIDs: Left ventricular internal dimension at end-systole; PAPi: Pulmonary artery pulsatility index; RA: Right atrial; RF: Regurgitant fraction; RV: Right ventricle; RVEDA: Right ventricular end-diastolic area; RVFAC: Right ventricular fractional area change; RVSP: Right ventricular systolic pressure; TAPSE: tricuspid annular plane systolic excursion; TAVR: Transcatheter aortic valve replacement; TV: Tricuspid valve

EFFECT OF BROMOCRIPTINE TREATMENT ON LEFT AND RIGHT VENTRICULAR FUNCTION IN PERIPARTUM CARDIOMYOPATHY

Peripartum cardiomyopathy (PPCM) is a rare but devastating cause of heart failure in peripartum women. At the time of diagnosis, approximately one-third of patients exhibit right ventricular (RV) dysfunction on echocardiography. Improvement in RV function has been associated with subsequent left

Uso de treprostinil sistémico en una paciente con hipertensión pulmonar grave, sin respuesta a la máxima terapia disponible

In high risk Pulmonary Arterial Hypertension (PAH) patients with functional class (FC) IV, specific therapy must be combined and must include systemic prostacyclin (PGI2), meanwhile they are enlisted for double lung transplant (DLT). In Chilean Public Health System, nebulized Iloprost is the only PGI2 available to combine with Sildenafil and either Ambrisentan or Bosentan as endothelin receptor antagonist. This association is not enough for severe cases with right ventricular (RV) dysfunction. The first case from the National Institute of Thorax as a referral center is presented now in a 24 years-old lady treated with treprostinil. She has severe PAH with DLT indication. Treprostinil is a PGI2 analog, for subcutaneous use in a dose from 1 to 40 ng/kg/min. She was extremely sick, with FC IV, she walked 2,500 pg/ml. Six months after being at intensive care unit with triple therapy (Sildenafil, ambrisentan and nebulized Iloprost) plus oxygen, diuretics and milrinone, she was finally discharged after receiving a 3 weeks treprostinil course. She came back to work two months later and her condition was more stable: FC III, she walked > 440 m at 6MWT, with a significant improvement in RV function with TAPSE = 19. Although ProBNP decreased to 1,491pg/ml,it was still high, pointing out the progressive nature of her disease. However, she met a better clinical condition which allows her to reach a much better quality of life from a personal, familial and social point of view.

Sacubitril/valsartan improves right ventricular function in a real-life population of patients with chronic heart failure: The Daunia Heart Failure Registry

BackgroundPrevious studies and case-series showed improvement in left ventricular (LV) function and reverse remodeling after sacubitril/valsartan therapy in real-world studies. We therefore aimed to evaluate whether also right ventricular (RV) function may improve after sacubitril/valsartan therapy. MethodsSixty consecutive patients with chronic heart failure and NYHA class II-III were followed up for 12 months after therapy with sacubitril/valsartan. Left and (RV) function was assessed at baseline and after 12 months of therapy. ResultsAt 12-month control, therapy with sacubitril/valsartan was associated with a significant improvement in a series of echo parameters: LVEF (p < 0.05), LV end-systolic volume (p < 0.01), left atrium area (p < 0.05).Right ventricular echo parameters were also improved after sacubitril/valsartan therapy: PAsP (31.0 ± 12.8 vs 34.7 ± 12.5 mmHg, p < 0.05), TAPSE (17.8 ± 3.9 vs 16.5 ± 4.0 mm, p < 0.001); mean PAsP reduction was 3.7 ± 11.4 mmHg (-6.3 ± 37.7%), mean TAPSE increase 1.3 ± 2.5 mm (+9.5 ± 15.7%).Indexed (%) improvement in PAsP (r 0.33, p < 0.01) and TAPSE (r −0.42, p < 0.01) values were proportional to baseline levels. Improvement in PAsP and TAPSE were independent of left ventricular improvements except for PAsP and end-systolic volumes (r 0.44, p < 0.01). ConclusionsIn a real world scenario, sacubitril/valsartan was associated with an improved RV function.

Impact of Mitral Valve Replacement on the Right Ventricle Function in Mitral Stenosis

Background: In patients with mitral stenosis (MS), right ventricular (RV) function may be altered due to an increase in the left atrial pressure and/or changes in pulmonary arteriolar vasculature or may be affected by rheumatic process directly. Aims: In this study we have evaluated the recovery of RV function upto 3 months in patients undergoing mitral valve replacement (MVR) using two dimensional and tissue Doppler echocardiographic indices (TDI). Materials and Methods: A total of 30 patients who were advised MVR were enrolled prospectively. All patients underwent MVR successfully. RV function was assessed using conventional and TDI pre-operatively, 1 week, and 3 months after surgery. Results: New York Heart Association (NYHA) functional class improved significantly at the end of one week. Mean transmitral gradient reduced postoperatively. Tricuspid regurgitation severity reduced significantly. Significant RV reverse remodelling was noted at the end of 3 months. Global RV function parameters fractional area change and RV Tei index improved significantly at the end of 3 months. In patients with mild to moderate pulmonary hypertension (PH), global RV function improved significantly, RV remodelling was seen. In patients with severe PH, both global and longitudinal functions did not improve at the end of 3 months follow up, though RV remodelling was noticed. Conclusion: In patients with severe rheumatic MS whenever per-cutaneous trans-mitral commissurotomy is not feasible, MVR promotes RV remodelling and improvement in RV function along with significant improvement in NYHA functional status. But this improvement in RV function was noted only in patients with mild to moderate PH rather than in patients with severe PH.