Impact of Cardiac Progenitor Cells on Heart Failure and Survival in Single Ventricle Congenital Heart Disease.

RATIONALE: Intracoronary administration of cardiosphere-derived cells (CDCs) in patients with single ventricles resulted in a short-term improvement in cardiac function. OBJECTIVE: To test the hypothesis that CDC infusion is associated with improved cardiac function and reduced mortality in patients with heart failure. METHODS AND RESULTS: We evaluated the effectiveness of CDCs using an integrated cohort study in 101 patients with single ventricles, including 41 patients who received CDC infusion and 60 controls treated with staged palliation alone. Heart failure with preserved ejection fraction (EF) or reduced EF was stratified by the cardiac function after surgical reconstruction. The main outcome measure was to evaluate the magnitude of improvement in cardiac function and all-cause mortality at 2 years. Animal studies were conducted to clarify the underlying mechanisms of heart failure with preserved EF and heart failure with reduced EF phenotypes. At 2 years, CDC infusion increased ventricular function (stage 2: +8.4±10.0% versus +1.6±6.4%, P=0.03; stage 3: +7.9±7.5% versus -1.1±5.5%, P<0.001) compared with controls. In all available follow-up data, survival did not differ between the 2 groups (log-rank P=0.225), whereas overall patients treated by CDCs had lower incidences of late failure (P=0.022), adverse events (P=0.013), and catheter intervention (P=0.005) compared with controls. CDC infusion was associated with a lower risk of adverse events (hazard ratio, 0.411; 95% CI, 0.179-0.942; P=0.036). Notably, CDC infusion reduced mortality (P=0.038) and late complications (P<0.05) in patients with heart failure with reduced EF but not with heart failure with preserved EF. CDC-treated rats significantly reversed myocardial fibrosis with differential collagen deposition and inflammatory responses between the heart failure phenotypes. CONCLUSIONS: CDC administration in patients with single ventricles showed favorable effects on ventricular function and was associated with reduced late complications except for all-cause mortality after staged procedures. Patients with heart failure with reduced EF but not heart failure with preserved EF treated by CDCs resulted in significant improvement in clinical outcome. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01273857 and NCT01829750.

Stem Cell Therapy in Heart Disease: Limitations and Future Possibilities.

Heart diseases are one of the major causes of morbidity and mortality worldwide. Despite major advances in drug and interventional therapies, surgical procedures, and organ transplantation, further research into new therapeutic options is still necessary. Stem cell therapy has emerged as one option for the treatment of a variety of heart diseases. Although a large number of clinical trials have shown stem cell therapy to be a promising therapeutic approach, the results obtained from these clinical studies are inconsistent, and stem cell-based improvements of heart performance and cardiac remodeling were found to be quite limited. Since the precise mechanisms underlying the therapeutic actions of stem cells are still under debate, researchers have developed a variety of strategies to improve and boost the potency of stem cells in repair. In this Reviews, we summarize both the current therapeutic strategies using stem cells and future directions for enhancing stem cell potency.

Intracoronary Cardiac Progenitor Cells in Single Ventricle Physiology: The PERSEUS (Cardiac Progenitor Cell Infusion to Treat Univentricular Heart Disease) Randomized Phase 2 Trial.

RATIONALE: Patients with single ventricle physiology are at high risk of mortality resulting from ventricular dysfunction. The preliminary results of the phase 1 trial showed that cardiosphere-derived cells (CDCs) may be effective against congenital heart failure. OBJECTIVE: To determine whether intracoronary delivery of autologous CDCs improves cardiac function in patients with single ventricle physiology. METHODS AND RESULTS: We conducted a phase 2 randomized controlled study to assign in a 1:1 ratio 41 patients who had single ventricle physiology undergoing stage 2 or 3 palliation to receive intracoronary infusion of CDCs 4 to 9 weeks after surgery or staged reconstruction alone (study A). The primary outcome measure was to assess improvement in cardiac function at 3-month follow-up. Four months after palliation, controls had an alternative option to receive late CDC infusion on request (study B). Secondary outcomes included ventricular function, heart failure status, somatic growth, and health-related quality of life after a 12-month observation. At 3 months, the absolute changes in ventricular function were significantly greater in the CDC-treated group than in the controls (+6.4% [SD, 5.5] versus +1.3% [SD, 3.7]; P=0.003). In study B, a late CDC infusion in 17 controls increased the ventricular function at 3 months compared with that at baseline (38.8% [SD, 7.7] versus 34.8% [SD, 7.4]; P<0.0001). At 1 year, overall CDC infusion was associated with improved ventricular function (41.4% [SD, 6.6] versus 35.0% [SD, 8.2]; P<0.0001) and volumes (P<0.001), somatic growth (P<0.0001) with increased trophic factors production, such as insulin-like growth factor-1 and hepatocyte growth factor, and quality of life, along with a reduced heart failure status (P<0.0001) and cardiac fibrosis (P=0.014) relative to baseline. CONCLUSIONS: Intracoronary infusion of CDCs after staged palliation favorably affected cardiac function by reverse remodeling in patients with single ventricle physiology. This impact may improve heart failure status, somatic growth, and quality of life in patients and reduce parenting stress for their families. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01829750.

Transcoronary cell infusion with the stop-flow technique in children with single-ventricle physiology.

BACKGROUND: Almost all reports on cardiac regeneration therapy have referred to adults, and only a few have focused on transcoronary infusion of cardiac progenitor cells using the stop-flow technique in children. METHODS: Intracoronary autologous cardiosphere-derived cell (CDC) transfer was conducted at Okayama University as a phase 1 clinical trial for seven patients with hypoplastic left heart syndrome between January 2011 and December 2012, and as a phase 2 clinical trial for 34 patients with single-ventricle physiology between July 2013 and March 2015. RESULTS: A total of 41 patients with single-ventricle physiology underwent transcoronary infusion of CDC with the stop-flow technique. The median age was 33 months (range, 5-70 months) and the median weight was 10.1 kg (range, 4.1-16.0 kg). Transient adverse events occurred during the procedure, including ST-segment elevation or depression, hypotension, bradycardia, and coronary artery vasospasm. All patients completely recovered. There were no major procedure-related adverse events. In this study, transcoronary infusion of CDC using the stop-flow technique was successfully completed in all patients. CONCLUSION: Transcoronary infusion of CDC using the stop-flow technique in children is a feasible and safe procedure.

Long-Term Results of Bilateral Pulmonary Artery Banding Versus Primary Norwood Procedure.

Bilateral pulmonary artery banding (PAB) has emerged to be an attractive option as an initial procedure for the treatment of hypoplastic left heart syndrome (HLHS), and some centers report excellent survival. However, its usage is variable among institutions and its true efficacy is unknown due to reporting biases. We aimed to describe the results of bilateral PAB use, preoperative risk factors, and long-term outcomes compared with primary Norwood procedure, using a national database. Infants who underwent bilateral PAB or Norwood procedure as an initial palliation for HLHS between January 2008 and December 2012 listed in the Japan Congenital Cardiovascular Surgery Database (JCCVSD) were included. The total number of patients diagnosed with HLHS was 334. Bilateral PABs were performed for 256 patients and primary Norwood procedures for 78 patients, as an initial procedure. Actuarial 5-year survival was 59.0%. The primary Norwood procedure group had better 5-year survival [75.5%; 95% confidence interval (CI) 63.2-84.1] than the bilateral PAB group (75.5 vs. 54.0%, log-rank p < 0.001). However, the bilateral PAB group had more significant risk factors. When the risk-adjusted outcomes were evaluated, there was no significant difference between the primary Norwood group and the bilateral PAB group (76.4 vs. 78.1%, log-rank p = 0.87) in higher volume institutions. The primary Norwood group had better 5-year survival than the bilateral PAB group, but preoperative risk was higher in the bilateral PAB group. Because outcomes are comparable when performed at higher HLHS volume institutions, proper patient selection is important in achieving good long-term result.

Intracoronary autologous cardiac progenitor cell transfer in patients with hypoplastic left heart syndrome: the TICAP prospective phase 1 controlled trial.

RATIONALE: Hypoplastic left heart syndrome (HLHS) remains a lethal congenital cardiac defect. Recent studies have suggested that intracoronary administration of autologous cardiosphere-derived cells (CDCs) may improve ventricular function. OBJECTIVE: The aim of this study was to test whether intracoronary delivery of CDCs is feasible and safe in patients with hypoplastic left heart syndrome. METHODS AND RESULTS: Between January 5, 2011, and January 16, 2012, 14 patients (1.8±1.5 years) were prospectively assigned to receive intracoronary infusion of autologous CDCs 33.4±8.1 days after staged procedures (n=7), followed by 7 controls with standard palliation alone. The primary end point was to assess the safety, and the secondary end point included the preliminary efficacy to verify the right ventricular ejection fraction improvements between baseline and 3 months. Manufacturing and intracoronary delivery of CDCs were feasible, and no serious adverse events were reported within the 18-month follow-up. Patients treated with CDCs showed right ventricular ejection fraction improvement from baseline to 3-month follow-up (46.9%±4.6% to 52.1%±2.4%; P=0.008). Compared with controls at 18 months, cardiac MRI analysis of CDC-treated patients showed a higher right ventricular ejection fraction (31.5%±6.8% versus 40.4%±7.6%; P=0.049), improved somatic growth (P=0.0005), reduced heart failure status (P=0.003), and lower incidence of coil occlusion for collaterals (P=0.007). CONCLUSIONS: Intracoronary infusion of autologous CDCs seems to be feasible and safe in children with hypoplastic left heart syndrome after staged surgery. Large phase 2 trials are warranted to examine the potential effects of cardiac function improvements and the long-term benefits of clinical outcomes. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01273857.

Decreased Serum Levels of High Mobility Group Box 1 (HMGB-1) after Graft Replacement or Stenting of Abdominal Aortic Aneurysm.

BACKGROUND: High-mobility group box 1 (HMGB-1) is a key substance mediating inflammation and development of atherosclerotic lesions (ALs), including abdominal aortic aneurysms (AAA). Serum levels of HMGB-1 are increased in patients with AAA than those in normal controls because the ALs in AAAs secrete HMGB-1. We therefore postulate that the serum HMGB-1 level should decrease after endovascular aortic repair (EVAR) or open aortic repair (OAR). However, there is no evidence of this in the literature. The purpose of this study was to investigate the changes in HMGB-1 levels after surgical intervention for AAA. We also aimed to determine if the HMGB-1 levels varied between the two procedures. METHODS: Serum HMGB-1 levels were determined in 24 patients with AAA and 25 healthy controls. Twelve of the 24 AAA patients underwent EVAR, whereas the other half underwent OAR. The relationship between HMGB-1 levels and presence of AAA or influence of operative methods on the serum HMGB-1 level were prospectively investigated. RESULTS: Serum HMGB-1 levels in AAA patients were significantly higher than those in healthy controls (9.4 ± 5.7 vs. 4.1 ± 2.0 ng/mL, P < 0.01). The serum HMGB-1 levels in both the EVAR group and the OAR group were significantly decreased from baseline at both 3 mo and 1 y after surgery. CONCLUSIONS: Removal or isolation of AL via surgical intervention significantly decreases serum HMGB-1 levels. The significant postoperative reduction in HMGB-1 levels suggests that important endocrinological changes occur after surgical treatment of AAA.

The global burden of paediatric heart disease.

An estimated 15 million children die or are crippled annually by treatable or preventable heart disease in low- and middle-income countries. Global efforts to reduce under-5 mortality have focused on reducing death from communicable diseases in low- and middle-income countries with little to no attention focusing on paediatric CHD and acquired heart disease. Lack of awareness of CHD and acquired heart disease, access to care, poor healthcare infrastructure, competing health priorities, and a critical shortage of specialists are important reasons why paediatric heart disease has not been addressed in low resourced settings. Non-governmental organisations have taken the lead to address these challenges. This review describes the global burden of paediatric heart disease and strategies to improve the quality of care for paediatric heart disease. These strategies would improve outcomes for children with heart disease.

Treat and Repair Strategy in Patients With Atrial Septal Defect and Significant Pulmonary Arterial Hypertension.

BACKGROUND: A therapeutic strategy in patients with atrial septal defect (ASD) and significant pulmonary arterial hypertension (PAH) remains controversial. This study aimed to assess the effect of PAH-specific medications and subsequent transcatheter shunt closure (ie, a treat and repair strategy) in these patients. METHODS AND RESULTS: Among 646 patients with ASD, 22 patients (mean age of 56±20 years) who had PAH [mean pulmonary artery pressure ≥25 mmHg and pulmonary vascular resistance (PVR) ≥3 Wood units] underwent successful transcatheter ASD closure. Prior to the procedure, 8 patients received PAH-specific medications (PHM group) and 14 patients did not (non-PHM group). Initially, the PHM group had higher PVR compared with non-PHM group (9.6±3.8 vs. 4.2±1.0 Wood units, P<0.01). After treatment with PAH-specific medications, PVR in this group decreased to 4.0±0.8 Wood units (P<0.01). No adverse events were observed in either the PHM or non-PHM group during or after the transcatheter procedure. In the PHM group, during a treatment period of 52±48 months, the World Health Organization Functional Classification significantly improved (3.0±0.5 to 2.0±0.0, P<0.01), as well as in the non-PHM group (2.1±0.6 to 1.5±0.5, P<0.01). CONCLUSIONS: Treat and repair strategy provided substantial improvement and no worsening of the WHO-FC, even in patients with ASD and significant PAH. Long-term hemodynamic follow-up is mandatory to evaluate the ultimate efficacy and safety of this new strategy.

Hybrid stage I palliation for hypoplastic left heart syndrome has no advantage on ventricular energetics: a theoretical analysis.

A hybrid procedure combining bilateral pulmonary artery banding with ductal stenting has recently been used as stage I palliation for hypoplastic left heart syndrome. However, the advantage of the hybrid procedure over the Norwood procedure on ventricular energetics remains unclear. To clarify this, we performed a computational analysis with a combination of time-varying elastance chamber model and modified three-element Windkessel vascular model. Although mean pulmonary artery (PA) pressure, pulmonary flow, and oxygen saturation were almost equivalent with the Norwood procedure, the hybrid procedure delivered higher systolic and lower diastolic systemic arterial pressures compared to the Norwood procedure with right ventricle (RV) to PA shunt. As a result, the hybrid procedure yielded increased systolic pressure-volume area and impaired mechanical efficiency. Therefore, the hybrid procedure has probably no advantage on ventricular energetics compared to the Norwood procedure with a RV-PA shunt.

Effect of the Pulsatile Extracorporeal Membrane Oxygenation on Hemodynamic Energy and Systemic Microcirculation in a Piglet Model of Acute Cardiac Failure.

The objective of this study was to compare the effects of pulsatile and nonpulsatile extracorporeal membrane oxygenation (ECMO) on hemodynamic energy and systemic microcirculation in an acute cardiac failure model in piglets. Fourteen piglets with a mean body weight of 6.08 ± 0.86 kg were divided into pulsatile (N = 7) and nonpulsatile (N = 7) ECMO groups. The experimental ECMO circuit consisted of a centrifugal pump, a membrane oxygenator, and a pneumatic pulsatile flow generator system developed in-house. Nonpulsatile ECMO was initiated at a flow rate of 140 mL/kg/min for the first 30 min with normal heart beating, with rectal temperature maintained at 36°C. Ventricular fibrillation was then induced with a 3.5-V alternating current to generate a cardiac dysfunction model. Using this model, we collected the data on pulsatile and nonpulsatile groups. The piglets were weaned off ECMO at the end of the experiment (180 min after ECMO was initiated). The animals did not receive blood transfusions, inotropic drugs, or vasoactive drugs. Blood samples were collected to measure hemoglobin, methemoglobin, blood gases, electrolytes, and lactic acid levels. Hemodynamic energy was calculated using the Shepard's energy equivalent pressure. Near-infrared spectroscopy was used to monitor brain and kidney perfusion. The pulsatile ECMO group had a higher atrial pressure (systolic and mean), and significantly higher regional saturation at the brain level, than the nonpulsatile group (for both, P < 0.05). Additionally, the pulsatile ECMO group had higher methemoglobin levels within the normal range than the nonpulsatile group. Our study demonstrated that pulsatile ECMO produces significantly higher hemodynamic energy and improves systemic microcirculation, compared with nonpulsatile ECMO in acute cardiac failure.

Urinary Albumin Levels Predict Development of Acute Kidney Injury After Pediatric Cardiac Surgery: A Prospective Observational Study.

OBJECTIVE: Mortality and morbidity of acute kidney injury (AKI) after cardiac surgery still remain high. The authors undertook the present study to evaluate the utility of early postoperative urinary albumin (uAlb) as a diagnostic marker for predicting occurrence of AKI and its severity in pediatric patients undergoing cardiac surgery. DESIGN: A prospective observational study. SETTING: A single-institution university hospital. PARTICIPANTS: All patients<18 years of age who underwent repair of congenital heart disease with cardiopulmonary bypass between July 2010 and July 2012 were included in the study. Neonates age<1 month were excluded from the study population. INTERVENTIONS: The association between uAlb and occurrence of AKI within 3 days after admission to the intensive care unit was investigated. Criteria from pediatric-modified Risk Injury Failure Loss and End-stage kidney disease (pRIFLE) were used to determine the occurrence of AKI. The value of uAlb was measured at intensive care unit admission immediately after cardiac surgery in all participants from whom a 5-mL urine sample was obtained. MEASUREMENTS AND MAIN RESULTS: Of 376 patients, AKI assessed by pRIFLE was identified in 243 (64.6%): 172 for risk (R; 45.7%), 44 for injury (I; 11.7%), and 27 for failure (F; 7.2%). One hundred thirty-three patients (35.4%) were classified as being without AKI (normal [N]) by pRIFLE. The concentration of uAlb was significantly higher in AKI patients than in non-AKI patients (median [interquartile range]): uAlb (µg/mL): 13.5 (6.4-39.6) v 6.0 (3.4-16), p<0.001; uAlb/Cr (mg/gCr): 325 (138-760) v 121 (53-269), p< 0.001. CONCLUSIONS: The utility of uAlb for prompt diagnosis of AKI was shown. Obtaining uAlb measurements early after pediatric cardiac surgery may be useful for predicting the occurrence and severity of AKI.

A prospective randomized trial comparing the clinical effectiveness and biocompatibility of heparin-coated circuits and PMEA-coated circuits in pediatric cardiopulmonary bypass.

OBJECT: We compared the clinical effectiveness and biocompatibility of poly-2-methoxyethyl acrylate (PMEA)-coated and heparin-coated cardiopulmonary bypass (CPB) circuits in a prospective pediatric trial. METHODS: Infants randomly received heparin-coated (n=7) or PMEA-coated (n=7) circuits in elective pediatric cardiac surgery with CPB for ventricular septum defects. Clinical and hematologic variables, respiratory indices and hemodynamic changes were analyzed perioperatively. RESULTS: Demographic and clinical variables were similar in both groups. Leukocyte counts were significantly lower 5 minutes after CPB in the PMEA group than the heparin group. Hemodynamic data showed that PMEA caused hypotension within 5 minutes of CPB. The respiratory index was significantly higher immediately after CPB and 1 hour after transfer to the intensive care unit (ICU) in the PMEA group, as were levels of C-reactive protein 24 hours after transfer to the ICU. CONCLUSION: Our study shows that PMEA-coated circuits, unlike heparin-coated circuits, cause transient leukopenia during pediatric CPB and, perhaps, systemic inflammatory respiratory syndrome after pediatric CPB.

[Delayed Diagnosis of Aortic Dissection Following Thrombolytic Therapy in a Patient with Acute Ischemic Stroke;Report of a Case].

Diagnosis of aortic dissection complicating cerebral ischemic stroke is difficult. A 60-year-old patient presented at an emergency department of a hospital with a sudden development of left-sided weakness, but without chest pain. During administration of recombinant tissue plasminogen activator with diagnosis of cerebral infarction, he developed symptomatic hypotension and was transferred to our hospital. His chest computed tomography revealed Stanford type A aortic dissection. Replacement of the ascending aorta and aortic arch was successfully performed on the 4th day.

Usefulness of high mobility group box 1 protein as a plasma biomarker in patient with peripheral artery disease.

Atherosclerosis is often associated with chronic vascular inflammation. High-mobility group box 1 protein (HMGB1) plays various roles, not only as a transcriptional regulatory factor in the nucleus, but also as an inflammatory mediator. A previous study suggested that fibrinogen is an important factor associated with atherosclerosis progression. The present study was performed to examine the levels of plasma HMGB1 protein in atherosclerosis patients. We studied 24 patients with peripheral artery disease (PAD) with atherosclerosis, and 10 healthy controls. We found that the concentrations of HMGB1 were increased in the plasma of the patients with atherosclerosis, and there were significant correlations between the plasma HMGB1 and fibrinogen levels. Plasma HMGB1 may play a key role in the pathogenesis of clinical and experimental atherosclerosis.

[Treatment strategy toward Fontan completion in hypoplastic left heart syndrome].

The Norwood procedure with right ventricle-pulmonary artery (RV-PA) conduit is thought to improve post-operative hemodynamics in hypoplastic left heart syndrome( HLHS). Prematurity( GA<37 weeks), body weight less than 2.5 kg and tricuspid regurgitation( TR)2+ or more were associated with mortality. For requiring better outcome, paralyzed ventilation, inherent N2 are indicated, to avoid preoperative high pulmonary blood flow followed by progressive TR. Rapid staged bilateral pulmonary artery banding( PAB) might improve the outcome for this high mortality group. As operative improvement, the distal neoaortic reconstruction was completed without any patch materials in most case. For achievement this, it is important that aortic arch and ascending aorta just opposite the site of the innominate artery were sutured inferiorly to extend the width of the aortic arch. Also we have developed a modified strategy to control RV-PA shunt flow, which is partial clipping on the ePTFE graft. Because significant TR associated with mortality, TR should be surgically treated at any sage of reconstruction. At bidirectional Glenn operation, 70% of patient were left the RV-PA conduit as additional flow. Hospital mortality after Fontan completion for HLHS is excellent with short averaging more than 95%. Extracardiac conduit with fenestration is indicated in all HLHS patients.

Staged repair for complete atrioventricular septal defect in patients weighing less than 4.0 kg.

OBJECTIVE: This study compared the mortality, left atrioventricular valve-related reoperation, and left atrioventricular valve competence in symptomatic neonates and small infants who underwent staged repair incorporating pulmonary artery banding or primary repair for complete atrioventricular septal defect. METHODS: Patients weighing less than 4.0 kg at the time of undergoing staged (n = 37) or primary (n = 23) repair for balanced complete atrioventricular septal defect between 1999 and 2022 were reviewed. The mean follow-up period was 9.1 years. Freedom from moderate or greater left atrioventricular valve regurgitation was estimated with the Kaplan-Meier method. RESULTS: The staged group included smaller children (median weight, 2.9 vs 3.7 kg) and a higher proportion of neonates (41% vs 4%). All patients in the staged group survived pulmonary artery banding and underwent intracardiac repair (median weight, 6.8 kg). After pulmonary artery banding, the severity of left atrioventricular valve regurgitation improved in 10 of 12 patients (83%) without left atrioventricular valve anomaly who had mild or greater left atrioventricular valve regurgitation and a left atrioventricular valve Z score greater than 0. Although survival and freedom from left atrioventricular valve-related reoperation at 15 years (P = .195 and .602, respectively) were comparable between the groups, freedom from moderate or greater left atrioventricular valve regurgitation at 15 years was higher in the staged group (P = .026). CONCLUSIONS: Compared with primary repair, staged repair for complete atrioventricular septal defect in children weighing less than 4.0 kg resulted in comparable survival and reoperation rates and better left atrioventricular valve competence. Pulmonary artery banding may mitigate secondary left atrioventricular valve regurgitation unless a structural valve abnormality exists. Selective deferred intracardiac repair beyond the neonatal and small-infancy period may still play an important role in low-weight patients.

Usefulness of balloon angioplasty for the right ventricle-pulmonary artery shunt with the modified Norwood procedure.

OBJECTIVE: We sought to evaluate the efficacy of balloon angioplasty (BA) for severely desaturated patients due to a stenotic right ventricle (RV) to pulmonary artery (PA) shunt following modified Norwood procedure. METHODS: Of 87 patients who underwent a Norwood procedure with the RV-PA shunt between February 1998 through March 2010, 22 (25%) patients underwent BA. The efficacy of BA was assessed by angiographic measurement of the changes in the internal diameters of the stenotic portions of the shunt, changes in arterial saturation and clinical outcomes. RESULTS: BA was performed for stenotic RV-PA shunts following stage I palliation (n = 17, 77%), or those placed as an additional blood source (n = 5, 23%, 3 patients awaiting biventricular repair, 2 patients following stage II palliation). The location of the BA was at the distal anastomosis in 12 (54.5%), proximal anastomosis in 21 (95.4%) and in the mid-portion of the shunt in 11 (50%) cases. The diameters of these three shunt portions were measured from the anterior-posterior and lateral angiographic images, increasing significantly after BA (p < 0.0001) in all. Arterial saturation significantly improved after BA in all cases (66.5 ± 4.3% to 79.4 ± 3.4%, p < 0.0001). Freedom from reintervention was 100%. All patients underwent subsequent elective planned surgery at an appropriate age with no mortality. CONCLUSIONS: A BA-alone strategy for a stenotic RV-PA shunt was effective for all three shunt portions, minimizing shunt-related premature surgical intervention.

Long-term effects of transcatheter closure of atrial septal defect on cardiac remodeling and exercise capacity in patients older than 40 years with a reduction in cardiopulmonary function.

BACKGROUND: Although it has been demonstrated that cardiac remodeling and exercise capacity improve after transcatheter closure of atrial septal defect (ASD), little is known about long-term benefits in middle-aged and elderly patients with a reduction in cardiopulmonary function. OBJECTIVES: To evaluate long-term extent and time course of improvements in cardiac remodeling and exercise capacity in those patients. METHODS: Twenty ASD patients ≥ 40 years of age with a reduction in cardiopulmonary function (predicted peak oxygen uptake [VO(2)] < 65%) were enrolled. Transthoracic echocardiography and cardiopulmonary exercise testing were performed at baseline and at 1 month, 3 months, 6 months, and >12 months after the procedure. RESULTS: At 1 month after the procedure, significant decreases in right ventricular (RV) end-diastolic diameter (38.2 ± 4.4 to 31.9 ± 4.4 mm; P < 0.001) and RV/left ventricular end-diastolic diameter ratio (0.95 ± 0.17 to 0.71 ± 0.13; P < 0.001) occurred, and they were maintained during the follow-up period. Normal RV size was achieved in 11 of 18 patients with RV enlargement. Predicted peak VO(2) did not change at 1 month and 3 months, but it improved significantly after 6 months (53.6 ± 6.5 to 62.1 ± 12.6%; P < 0.01). Sixteen of the 20 patients showed improved predicted peak VO(2). CONCLUSIONS: Cardiac remodeling and exercise capacity could be improved over the long-term period after transcatheter closure of ASD in middle-aged and elderly patients with a reduction in cardiopulmonary function. There were differences in the time course of improvement between cardiac remodeling and exercise capacity in those patients.

Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction.

Mesenchymal stem cells are multipotent cells that can differentiate into cardiomyocytes and vascular endothelial cells. Here we show, using cell sheet technology, that monolayered mesenchymal stem cells have multipotent and self-propagating properties after transplantation into infarcted rat hearts. We cultured adipose tissue-derived mesenchymal stem cells characterized by flow cytometry using temperature-responsive culture dishes. Four weeks after coronary ligation, we transplanted the monolayered mesenchymal stem cells onto the scarred myocardium. After transplantation, the engrafted sheet gradually grew to form a thick stratum that included newly formed vessels, undifferentiated cells and few cardiomyocytes. The mesenchymal stem cell sheet also acted through paracrine pathways to trigger angiogenesis. Unlike a fibroblast cell sheet, the monolayered mesenchymal stem cells reversed wall thinning in the scar area and improved cardiac function in rats with myocardial infarction. Thus, transplantation of monolayered mesenchymal stem cells may be a new therapeutic strategy for cardiac tissue regeneration.