Beneficial effects of mesenchymal stem cell delivery via a novel cardiac bioscaffold on right ventricles of pulmonary arterial hypertensive rats.

Right ventricular failure (RVF) is a common cause of death in patients suffering from pulmonary arterial hypertension (PAH). The current treatment for PAH only moderately improves symptoms, and RVF ultimately occurs. Therefore, it is necessary to develop new treatment strategies to protect against right ventricle (RV) maladaptation despite PAH progression. In this study, we hypothesize that local mesenchymal stem cell (MSC) delivery via a novel bioscaffold can improve RV function despite persistent PAH. To test our hypothesis, we induced PAH in adult rats with SU5416 and chronic hypoxia exposure; treated with rat MSCs delivered by intravenous injection, intramyocardial injection, or epicardial placement of a bioscaffold; and then examined treatment effectiveness by in vivo pressure-volume measurement, echocardiography, histology, and immunohistochemistry. Our results showed that compared with other treatment groups, only the MSC-seeded bioscaffold group resulted in RV functional improvement, including restored stroke volume, cardiac output, and improved stroke work. Diastolic function indicated by end-diastolic pressure-volume relationship was improved by the local MSC treatments or bioscaffold alone. Cardiomyocyte hypertrophy and RV fibrosis were both reduced, and von Willebrand factor expression was restored by the MSC-seeded bioscaffold treatment. Overall, our study suggests a potential new regenerative therapy to rescue the pressure-overload failing RV with persistent pulmonary vascular disease, which may improve quality of life and/or survival of PAH patients. NEW & NOTEWORTHY We explored the effects of mesenchymal stem cell-seeded bioscaffold on right ventricles (RVs) of rats with established pulmonary arterial hypertension (PAH). Some beneficial effects were observed despite persistent PAH, suggesting that this may be a new therapy for RV to improve quality of life and/or survival of PAH patients.

Isolated Severe Right Ventricular Hypertrophic Cardiomyopathy.

A 26-year-old woman with a diagnosis of congenital heart disease was admitted to the hospital with exertional dyspnea, cyanotic complexion, and bilateral lower limb edema. All tests revealed isolated severe right ventricular hypertrophy. She was in poor condition, with a diminishing chance for routine surgical treatment, so she was scheduled for orthotopic homologous heart transplantation. After the operation, isolated severe right ventricular hypertrophic cardiomyopathy was confirmed histologically and pathologically. After the operation, the patient's cardiac function was normal. Exertional dyspnea, cyanotic complexion, and bilateral lower limb edema all improved postoperatively.

Investigating the characteristics of echocardiogram, surgical treatment, chromosome and prognosis for fetal right heart enlargement: A STROBE-compliant article.

The prognosis of right heart enlargement varies according to different etiologies. The purpose of this study was to investigate the characteristics of echocardiogram, surgical treatment, chromosome and prognosis for fetal right heart enlargement.The foetal echocardiogram was performed on 3987 pregnant women, and then 88 fetuses with right heart enlargement were identified. The data about prenatal and postnatal echocardiograms, postnatal cardiac surgical treatment, karyotype analysis and autopsy after induced labor were analyzed in the 88 fetuses.Except the 1111 cases that had loss of follow-up, 2876 cases had complete data. Among the 2876 cases, right heart enlargement was identified in 88 fetuses. Of the 88 fetuses, 15 had total atrioventricular septal defect (unbalanced type: right ventricular dominance), 15 Ebstein's anomaly, 18 fallot tetrad, 14 double outlet right ventricle, 13 total anomalous pulmonary venous drainage, and 13 premature closure of ductus arteriosus. Chromosomal abnormality was found in 12 cases.There are many etiological factors causing right heart enlargement. The prognosis is better in the fetuses with single heart malformation than in the fetuses who have extracardiac malformation or/and chromosomal abnormality besides heart malformation. Fetal echocardiography combined with karyotype analysis can provide important bases for evaluating the prognosis of fetuses with right heart enlargement.

First human implant of the Alterra Adaptive PrestentTM : A new self-expanding device designed to remodel the right ventricular outflow tract.

Current balloon expandable transcatheter valves have limited applicability to patients with "native" right ventricular outflow tracts (RVOT), meaning those who have had previous surgery and are left with large, compliant, irregular RVOT. The Alterra Adaptive PrestentTM is a self-expanding, partially covered stent that was designed to internally reconfigure these types of RVOT, making them suitable for implantation of a commercially available balloon expandable heart valve, the SAPIEN 3. Herein, we describe the first human implant of this device.

Right Ventricular Enlargement within Months of Arteriovenous Fistula Creation in 2 Hemodialysis Patients.

Surgically created arteriovenous fistulae (AVF) for hemodialysis can contribute to hemodynamic changes. We describe the cases of 2 male patients in whom new right ventricular enlargement developed after an AVF was created for hemodialysis. Patient 1 sustained high-output heart failure solely attributable to the AVF. After AVF banding and subsequent ligation, his heart failure and right ventricular enlargement resolved. In Patient 2, the AVF contributed to new-onset right ventricular enlargement, heart failure, and ascites. His severe pulmonary hypertension was caused by diastolic heart failure, diabetes mellitus, and obstructive sleep apnea. His right ventricular enlargement and heart failure symptoms did not improve after AVF ligation. We think that our report is the first to specifically correlate the echocardiographic finding of right ventricular enlargement with AVF sequelae. Clinicians who treat end-stage renal disease patients should be aware of this potential sequela of AVF creation, particularly in the upper arm. We recommend obtaining preoperative echocardiograms in all patients who will undergo upper-arm AVF creation, so that comparisons can be made postoperatively. Alternative consideration should be given to creating the AVF in the radial artery, because of less shunting and therefore less potential for right-sided heart failure and pulmonary hypertension. A multidisciplinary approach is optimal when selecting patients for AVF banding or ligation.

The development of a pseudo-chamber after balloon pulmonary angioplasty: long-term complications of balloon pulmonary angioplasty.

We experienced a rare complication where extravasation developed a pseudo-chamber long after the balloon pulmonary angioplasty for supravalvular pulmonary stenosis. A 3-month-old girl was diagnosed with an anomalous origin of the left coronary artery from the pulmonary artery. She underwent the Takeuchi procedure at 10 months of age. During the follow-up, the supravalvular pulmonary stenosis deteriorated, and was treated by balloon pulmonary angioplasty with the double balloon technique catheter at 6 years of age. Angiography at the main pulmonary artery showed a small amount of extravasation contrast medium after the procedure. Follow-up echocardiography showed a diminished extravasation hemorrhage. Twelve years later, right ventricular enlargement due to pulmonary regurgitation had been observed on echocardiography. In addition, abnormal echo free space was detected at the left posterior of the left atrium. Enhanced computed tomography clearly demonstrated there was an orifice and extent of the pseudo-chamber. Surgical findings revealed a large tear just distal to the coronary tunnel. We speculated that extravasation blood was limited in the perivascular area early after the procedure but eventually reached the non-adhesive oblique pericardial sinus with age. Consequently, pulmonary to oblique pericardial sinus communication was established and looked like a pseudo-chamber long after the procedure. In conclusion, even if extravasation seems to be limited immediately after the balloon pulmonary angioplasty, it could expand for non-adhesive space and could develop a huge blood space like chamber. Long-term careful observation should be necessary for extravasation of pulmonary artery even with surgical adhesion.

Transmural dispersion of repolarization and cardiac remodeling in ventricles of rabbit with right ventricular hypertrophy.

INTRODUCTION: Recent publications demonstrated that rabbits with right ventricular hypertrophy (RVH) possess high sensitivity and specificity for drug-induced arrhythmias. However, the underlying mechanism has not been elucidated. This study aimed to evaluate RVH induced changes in cardiac remodeling especially the transmural dispersion of repolarization (TDR), epicardial monophasic action potentials (MAP), and hERG mRNA expression in rabbits. METHODS: New Zealand White rabbits (n=13) were divided into 2 groups: sham operated (SHAM, n=6) and pulmonary artery banding (PAB, n=7). PAB was induced by narrowing the pulmonary artery. Twenty weeks after surgery, hemodynamic, cardiac function, electrocardiograms, and MAP were obtained from PAB compared with SHAM. After measurement, rabbits were sacrificed to collect ventricular myocardium for histopathological analysis and measurement of hERG mRNA expression by real time PCR. RESULTS: After 20weeks, the % HW to BW ratio of whole heart and right ventricle (RV) and left and right ventricular free wall thickness was significantly increased in PAB when compared with those in SHAM. PAB has a significant electrical remodeling as demonstrated by lengthening of QT, QTc intervals, and increased Tp-Te duration. PAB also has a significant functional remodeling verified by decreased contractility index of RV and lengthened time constant of relaxation of LV. MAP of RV epicardium was significantly shortened in PAB consistently with increased hERG mRNA expression at the epicardium of RV. DISCUSSION: The rabbit with PAB demonstrates cardiac remodeling diastolic and systolic dysfunctions. These rabbits also demonstrate increased TDR and electrical remodeling related to the change of hERG mRNA expression which may be prone to develop arrhythmias.

Effects of bariatric surgery on right ventricular structure and function.

AIM: Left ventricular (LV) changes associated with obesity, including LV hypertrophy and impaired LV function, have been shown to be reverted by bariatric surgery. Little is known about the effects of bariatric procedures on right ventricle (RV). We analyzed the literature in order to provide a comprehensive information on RV structural and functional changes, as assessed by imaging techniques, after bariatric surgery. METHODS AND RESULTS: The studies were identified by the following search terms: 'bariatric surgery', 'obesity', 'left ventricle', 'right ventricle', 'left ventricular hypertrophy', 'right ventricular hypertrophy', 'cardiac hypertrophy', 'ventricular dysfunction', 'echocardiography', 'magnetic resonance imaging' and 'cardiac imaging techniques'.In a pooled population of 537 obese patients with preserved systolic function enrolled in eight studies, bariatric surgery induced beneficial effects on RV morphology and function; the procedures reverted obesity-related right ventricular hypertrophy as suggested by a significant decrease in RV mass, and improved systolic and diastolic RV performance as assessed by traditional and newer echocardiographic indexes. Decrements in body mass index and improvement in obstructive sleep apnea were major factors independently related to the improved RV structure and function. CONCLUSION: The present review shows that bariatric surgery exerts beneficial effects on RV structure and function in morbidly obese patients. As RV changes are independent predictors of outcomes, improvement of RV structure and function may contribute to the cardioprotective effects of bariatric surgery.

Early and late outcomes of total repair of tetralogy of Fallot: risk factors for late right ventricular dilatation.

OBJECTIVES: This study was undertaken to assess the early and long-term results of total repair of tetralogy of Fallot (TOF) and to identify the risk factors associated with late right ventricular (RV) dilatation. METHODS: The medical records of 326 patients (male:female = 192:134) who underwent total repair of TOF at Pusan National and Dong-A University Hospitals between July 1991 and May 2011 were retrospectively reviewed. Median age and weight at the time of operation were 13.0 months and 8.7 kg, respectively. Right ventricular end-diastolic dimensions and left ventricular end-diastolic dimensions were obtained during follow-up echocardiography to identify the risk factors associated with late RV dilatation. RESULTS: There were one operative death (0.3%) and 8 late deaths (2.5%). Of late deaths, two were related to operation-related cardiac problems. Overall survival rates at 5, 10, and 15 years were 97.0%, 95.4%, and 95.4%, and the corresponding freedom from cardiac death were 98.8%, 98.8%, and 98.8%, respectively. Freedom from re-operation and re-intervention were 84.4%, 74.2% and 74.2%. Six patients underwent pulmonary valve replacement during the follow-up period. Transannular patch (P = 0.036) and postoperative ventilator support period (P < 0.001) were found to be significant risk factors of late RV dilatation in multivariate analysis. CONCLUSIONS: Total correction of TOF can be performed with a very low mortality rate. However, the postoperative re-operation or re-intervention rates remain relatively high. Late RV dilatation after total repair of TOF was found to be associated with transannular patch enlargement and a longer postoperative ventilator support period.

A unique case of two sources of right ventricle enlargement in tetralogy of Fallot.

The most common long-term sequelae of tetralogy of Fallot (TOF) are related to acquired late postsurgical pulmonary valve pathology. This is often in the form of pulmonic insufficiency (PI) ultimately leading to right ventricular (RV) enlargement and failure, which may necessitate pulmonary valve replacement. We present a case of severe PI in TOF with an incidental large circumflex to RV fistula and single-vessel coronary artery stenosis in a patient with an enlarged RV. The diagnostic dilemma was to determine whether the RV enlargement was caused by severe PI, shunting from the coronary fistula, or a combination of both.

Energy transfer ratio as a metric of right ventricular efficiency in repaired congenital heart disease.

OBJECTIVE: With the success of early repair, continued functional assessment of repaired congenital heart disease is critical for improved long-term outcome. Pulmonary regurgitation, which is one of the main postoperative sequelae of congenital heart disease involved with the right ventricle (RV) such as tetralogy of Fallot and transposition of the great arteries, results in progressive RV dilatation coupled with pulmonary artery (PA) obstruction causing elevated RV pressures. The appropriate timing of intervention to correct these postoperative lesions remains largely subjective. In the present study, we evaluated an energy-based end point, namely energy transfer ratio (eMPA ), to assess the degree of RV and PA inefficiency in a group of congenital heart disease patients with abnormal RV-PA physiology. METHODS: Eight patients with abnormal RV-PA physiology and six controls with normal RV-PA physiology were investigated using a previously validated technique that couples cardiac magnetic resonance imaging and invasive pressure measurements. RESULTS: The mean eMPA of the patient group (0.56 ± 0.33) was significantly lower (P <.04) than that of the control group (1.56 ± 0.85), despite the fact that the patient group had a significantly higher RV stroke work indexed to body surface area (RV SWI ) than the control group (0.205 ± 0.095 J/m(2) vs. 0.090 ± 0.038 J/m(2) ; P <.02). CONCLUSION: We determined that the patients had inefficient RV-PA physiology due to a combination of RV dilatation with pulmonary regurgitation and RV outflow obstruction leading to an elevated end-systolic pressure. Using coupled magnetic resonance imaging and invasive pressure measurements, eMPA is determined to be a sensitive energy-based end point for measuring RV-PA efficiency. It may serve as a diagnostic end point to optimize timing of intervention.

Right ventricular reduction for repair of functional tricuspid valve regurgitation: one-year follow up.

BACKGROUND AND AIM OF THE STUDY: The study aim was to assess the impact of reducing the right ventricular (RV) cavity in order to optimize the outcome of tricuspid valve (TV) repair in cases of functional tricuspid regurgitation (FTR) with dilated right ventricle. METHODS: Between May 2007 and February 2010, a total of 17 patients (six males, 11 females; mean age 69.5 +/- 10.1 years; mean logistic EuroSCORE 24 +/- 13%) with severe FTR and severe RV dilation were included. Echocardiography and magnetic resonance imaging (MRI) were performed for geometric assessment of the right ventricle. Intraoperatively, the lateral RV free wall was plicated to reduce the RV cavum to approximate the papillary muscles and decrease tethering of the TV; a conventional ring annuloplasty was then performed. Follow up included echocardiography and MRI at one month and one year postoperatively. RESULTS: The mean operative time was 157 +/- 30 min, and the cross-clamp time 63 13 min. Postoperatively, the mean bleeding volume was 486 +/- 455 ml, the rethoracotomy rate 5.9%, intensive therapy unit (ITU) stay 6.0 +/- 4.4 days, and hospital stay 19.0 +/- 8.8 days. In-hospital mortality was 17.6%. The mean follow up was 14.4 +/- 2.4 months. The one-year follow up revealed a survival of 82.3%, a slight decrease in RV ejection fraction (from 33.5 +/- 4.2% to 31.7 +/- 5.7%; p = 0.13), a significant reduction in the RV end-diastolic volume index (from 160 +/- 15.6 to 128 +/- 10 ml/m2; p = 0.0001), a reduction in TV tenting area (from 3.3 +/- 0.9 to 0.9 +/- 0.3 cm2; p = 0.0001), and a significant reduction in the ratio of TR jet to right atrial surface area (from 54.8 +/- 8.2% to 14.1 +/- 3.5%; p = 0.0001). CONCLUSION: In cases of FTR, RV dilation may be considered as a correctable factor at subvalvular level to optimize the outcome of TV repair.

Quadricuspid pulmonary valve: computed tomography case series and review of relevant literature.

Quadricuspid pulmonary valve (QPV) is a rare congenital cardiac entity. The recognition of QPV has clinical significance as it can cause pulmonary valve dysfunction. It is also important to recognize this condition in patients undergoing the Ross procedure. We report a case of QPV diagnosed by computed tomography with associated pulmonary stenosis and right ventricular hypertrophy.

Biventricular structural and functional responses to aortic constriction in a rabbit model of chronic right ventricular pressure overload.

OBJECTIVES: Chronic right ventricular (RV) pressure overload results in pathologic RV hypertrophy and diminished RV function. Although aortic constriction has been shown to improve systolic function in acute RV failure, its effect on RV responses to chronic pressure overload is unknown. METHODS: Adjustable vascular banding devices were placed on the main pulmonary artery and descending aorta. In 5 animals (sham group), neither band was inflated. In 9 animals (PAB group), only the pulmonary arterial band was inflated, with adjustments on a weekly basis to generate systemic or suprasystemic RV pressure at 28 days. In 9 animals, both pulmonary arterial and aortic devices were inflated (PAB + AO group), the pulmonary arterial band as for the PAB group and the aortic band adjusted to increase proximal systolic blood pressure by approximately 20 mm Hg. Effects on the functional performance were assessed 5 weeks after surgery by conductance catheters, followed by histologic and molecular assessment. RESULTS: Contractile performance was significantly improved in the PAB + AO group versus the PAB group for both ventricles. Relative to sham-operated animals, both banding groups showed significant differences in myocardial histologic and molecular responses. Relative to the PAB group, the PAB + AO group showed significantly decreased RV cardiomyocyte diameter, decreased RV collagen content, and reduced RV expression of endothelin receptor type B, matrix metalloproteinase 9, and transforming growth factor ß genes. CONCLUSIONS: Aortic constriction in an experimental model of chronic RV pressure overload not only resulted in improved biventricular systolic function but also improved myocardial remodeling. These data suggest that chronically increased left ventricular afterload leads to a more physiologically hypertrophic response in the pressure-overloaded RV.

Genetic determinants of right-ventricular remodeling after tetralogy of Fallot repair.

BACKGROUND: Hypoxia-inducible factor (HIF1A) regulates the myocardial response to hypoxia and hemodynamic load. We investigated the association of HIF1A variants with right-ventricular (RV) remodeling after tetralogy of Fallot (TOF) repair. METHODS: Children with TOF were genotyped for three single-nucleotide polymorphisms in HIF1A. Genotypes were analyzed for association with RV myocardial protein expression and fibrosis at complete repair (n = 42) and RV dilation, fractional area change, and freedom from pulmonary valve/conduit replacement on follow-up. RESULTS: In 180 TOF patients, mean age at repair was 1.0 ± 0.8 y with follow-up at 9.0 ± 3.5 y; 82% had moderate to severe pulmonary insufficiency. Freedom from RV reinterventions at 5, 10, and 15 y was 92, 84, and 67%, respectively. Patients with more functioning HIF1A alleles had higher transforming growth factor ß1 expression and more fibrosis at initial repair as compared with controls (P < 0.05). During follow-up, patients with more functioning HIF1A alleles showed less RV dilation, better preservation of RV function, and greater freedom from RV reinterventions (P < 0.05). This was confirmed in a replication cohort of 69 patients. CONCLUSION: In children who have had TOF repair, a lower number of functioning HIF1A alleles was associated with RV dilation and dysfunction, suggesting that hypoxia adaptation in unrepaired TOF may influence RV phenotype after repair.

Effects of autologous bone marrow mononuclear cells implantation in canine model of pulmonary hypertension.

BACKGROUND: We investigated the safety and feasibility of intratracheal administration of autologous bone marrow-derived mononuclear cells (ABM-MNCs) and observed the effects in a canine model of pulmonary hypertension (PH). METHODS AND RESULTS: The PH model was induced by intravenous injection of 3mg/kg dehydromonocrotaline (DMCT) via the right atrium. Two weeks after DMCT administration, the animals received 4 different treatments (n=10 in each group): (I) negative control group; (II): ABM-MNCs group; (III) PH group; (IV) PH+ABM-MNCs group. Six weeks after injection of cells (107), the hemodynamic data were significantly improved in group IV compared with group III (P<0.05). The ratio of right ventricular weight to left ventricular plus septal weight was significantly decreased in group IV compared with group III (P<0.05). The mRNA levels of vascular endothelial growth factor, preproendothelin-1, interleukin-6 and tumor necrosis factor-α were significantly improved in group IV compared with group III (P<0.05). The immunofluorescence result showed that 6 weeks after administration ABM-MNCs could differentiate into pulmonary vascular endothelial cells. CONCLUSIONS: Six weeks after intratracheal administration, ABM-MNCs significantly improved the impairment caused by DMCT in a canine model of PH (ie, decreased pulmonary arteriolar narrowing, alveolar septum thickening and right ventricular hypertrophy, enhanced angiogenesis) and this provides a firm foundation for a clinical trial.

An unknown complication of peripherally inserted central venous catheter in a patient with ventricular assist device.

We report an unknown complication of peripherally inserted central venous catheter in a patient with Ventricular Assist Device. This rare complication led to the failure of the right ventricular assist device, which could be detrimental in patients with dilated cardiomyopathy.