Takaya Hoashi

Skeletal myoblast sheet transplantation improves the diastolic function of a pressure-overloaded right heart

OBJECTIVE The development of right ventricular dysfunction has become a common problem after surgical repair of complex congenital heart disease. A recent study reported that tissue-engineered skeletal myoblast sheet transplantation improves left ventricular function in patients with dilated and ischemic cardiomyopathy. Therefore myoblast sheet transplantation might also improve ventricular performance in a rat model of a pressure-overloaded right ventricle. METHODS Seven-week-old male Lewis rats underwent pulmonary artery banding. Four weeks after pulmonary artery banding, myoblast sheet transplantation to the right ventricle was performed in the myoblast sheet transplantation group (n = 20), whereas a sham operation was performed in the sham group (n = 20). RESULTS Four weeks after performing the procedure, a hemodynamic assessment with a pressure-volume loop showed a compensatory increase in systolic function in both groups. However, only the myoblast sheet transplantation group showed a significant improvement in the diastolic function: end-diastolic pressure (sham vs myoblast sheet transplantation, 10.3 +/- 3.1 vs 5.0 +/- 3.7 mm Hg; P < .001), time constant of isovolumic relaxation (11.1 +/- 2.5 vs 7.6 +/- 1.2 ms, P < .001), and end-diastolic pressure-volume relationship (16.1 +/- 4.5 vs 7.6 +/- 2.4/mL, P < .005). The right ventricular weight and cell size similarly increased in both groups. A histologic assessment demonstrated significantly suppressed ventricular fibrosis and increased capillary density in the myoblast sheet transplantation group in comparison with those in the sham group. Reverse transcription-polymerase chain reaction demonstrated an increased myocardial gene expression of hepatocyte growth factor and vascular endothelial growth factor in the myoblast sheet transplantation group but not in the sham group. CONCLUSIONS Skeletal myoblast sheet transplantation improved the diastolic dysfunction and suppressed ventricular fibrosis with increased capillary density in a rat model of a pressure-overloaded right ventricle. This method might become a novel strategy for the myocardial regeneration of right ventricular failure in patients with congenital heart disease.

Combined autologous cellular cardiomyoplasty using skeletal myoblasts and bone marrow cells for human ischemic cardiomyopathy with left ventricular assist system implantation: Report of a case

Myocardial regeneration therapy shows great promise as a treatment for heart failure. We recently introduced combined autologous cellular cardiomyoplasty with skeletal myoblasts and bone marrow cells as a treatment for human ischemic cardiomyopathy. We report the results of our first clinical trial of this technique, used to treat a patient with severe heart failure caused by ischemic cardiomyopathy who was being managed with a left ventricular assist system (LVAS). After combined cell transplantation, the patient showed signs of improved cardiac performance and angiogenesis, and reduced fibrosis.

Cardiac Resynchronization Therapy for Various Systemic Ventricular Morphologies in Patients With Congenital Heart Disease

BACKGROUND Cardiac resynchronization therapy (CRT) can result in functional improvement and reduced mortality in patients with medically refractory heart failure. Although CRT is reportedly effective in patients with congenital heart disease (CHD), it is still controversial in patients who have systemic right ventricle. METHODS AND RESULTS: Twenty CHD patients treated with CRT since 2006 were divided into 3 groups based on systemic ventricular (sysV) morphology (7 with left ventricle [sLV], 7 with right ventricle [sRV], and 6 with unbalanced 2 ventricles as a single-ventricular physiology [sBV]). The acute effects of CRT on hemodynamics and sysV function before device implantation was retrospectively evaluated and the chronic (≥6 months) effects of CRT on late outcomes was assessed. In our CHD populations, sysV volume index was reduced from 139±41 to 118±33 ml/m(2)(P=0.04) after CRT, and there was significant improvement in B-type natriuretic peptide levels (from 341±384 to 160±152 pg/ml, P=0.01) and New York Heart Association (NYHA) functional class (from 2.1±0.6 to 1.8±0.7, P=0.02) on a late outcome. The sRV group did not show a late sysV volume reduction despite significant QRS shortening, and an increase of sysV peak dP/dt in the acute study differed from that of other groups. CONCLUSIONS CRT improves late hemodynamic and functional status in sLV and sBV CHD patients with a dyssynchronized sysV. However, an acute CRT effect cannot guarantee long-term benefit in sRV patients.

Optimal pacing sites for cardiac resynchronization therapy for patients with a systemic right ventricle with or without a rudimentary left ventricle.

AIMS This study aims to assess the impact of pacing sites on the effectiveness of cardiac resynchronization therapy (CRT) in systemic right ventricle (sRV) patients with/without a rudimentary left ventricle (rLV). METHODS AND RESULTS We evaluated 13 procedures in 11 sRV patients with a wide QRS (>150 ms). Based on the digitalization results of ventriculography, long-axis dyssynchrony (LD) was defined as extremely delayed right ventricular (RV) outflow tract movement: ≥100 ms delay from the RV apical contraction, and short-axis dyssynchrony (SD) was defined as a paradoxical contraction between the rLV and sRV caused by a conduction delay between the two ventricles. During the follow-up period (2.1 ± 1.9 years), the response rates were 71% (5/7) and 33% (2/6) in the sRV patients with and without an rLV, respectively (P = ns). Following the CRT, the QRS duration remained similar between the responders and nonresponders. Among five responders with an rLV, the leads were placed in the longitudinal RV direction in two with LD, longitudinal RV direction with fusion of the intrinsic QRS in two with LD + SD, and laterally on opposite sides of both ventricles in one with SD. Among two responders without an rLV, the leads were placed in the longitudinal RV direction in those two with LD. CONCLUSIONS In sRV patients with LD with/without an rLV, the leads should be placed at furthest sites in the longitudinal RV direction. In patients with an rLV and SD, the leads should be placed laterally on opposite sides of both ventricles.

Anatomic Repair for Corrected Transposition With Left Ventricular Outflow Tract Obstruction

BACKGROUND We investigated the long-term outcomes of anatomic repair for congenitally corrected transposition of great arteries (ccTGA) and its variant associated with left ventricular outflow tract obstruction (LVOTO) and ventricular septal defect (VSD). METHODS From 1987 to 2011, 47 patients (27 with pulmonary atresia and 20 with pulmonary stenosis) with ccTGA and its variant associated with LVOTO and VSD underwent anatomic repair. The mean operative age was 5.5 ± 3.7 years old (range, 1.6 to 21.3). The preoperative right ventricular end-diastolic volume was 133% ± 31% (81 to 222) of their normal size. The atrial switch procedure was Mustard in 31 patients and Senning in 16, with the latter used in all from 2002. RESULTS The mean follow-up period was 11.6 ± 7.3 years (maximum, 22.7). The VSD was concomitantly enlarged in 4 patients and Damus-Kaye-Stansel (DKS) anastomosis was added in 9 patients with pulmonary stenosis and restrictive VSD. The overall survival rate at 20 years was 70.2% and no mortality has been observed in 21 consecutive patients since 1997. No patient required reoperation for the postoperative systemic ventricular outflow tract obstruction. A surgical heart block developed in 1 patient (2.1%) who underwent concomitant VSD enlargement. None of the patients developed a moderate or greater aortic or neo-aortic regurgitation. CONCLUSIONS Recent outcomes after anatomic repair for congenitally corrected transposition of great arteries associated with LVOTO and VSD were excellent. For patients with pulmonary stenosis and restrictive VSD, additional DKS anastomosis seems to be an effective approach to avoid postoperative systemic ventricular outflow tract obstruction and surgical heart block.

Long-term results of treatments for functional single ventricle associated with extracardiac type total anomalous pulmonary venous connection

OBJECTIVES Surgical outcomes of patients with functional single ventricle have improved, though those for patients whose condition is complicated by extracardiac type total anomalous pulmonary venous connection (TAPVC) remain poor. We retrospectively reviewed our 21 years of surgical experiences with this challenging group. METHODS From 1990 to 2010, 48 consecutive patients with functional single ventricle complicated by extracardiac TAPVC (26 males, 46 with right atrial isomerism) underwent initial surgical palliation at our centre. The median age and body weight at surgery were 69 days and 3.5 kg, respectively. The type of TAPVC was supracardiac in 31 patients, infracardiac in 14 and mixed type in 3. TAPVC was repaired in 25 patients before bidirectional Glenn (BDG) and 18 at BDG, while it remained in 3 patients. Since 2007, stent implantation for obstructive drainage veins for patients with preoperative pulmonary venous obstruction and sutureless marsupialization for relief of postoperative pulmonary venous stenosis (PVS) have been initiated. The mean follow-up period was 4.2 ± 5.1 years. RESULTS The overall survival rates at 1, 3 and 5 years after the initial surgical intervention were 58.3, 41.1 and 31.3%, respectively. Sixteen patients achieved the Fontan operation (33.3%). The freedom from postoperative PVS rates at 1 and 3 years after repair was 68.7 and 63.4%, respectively. Univariate analysis detected that infracardiac TAPVC (P = 0.036), coexisting major aortopulmonary collaterals (P = 0.017), and TAPVC repair before BDG (P = 0.036) all reduced survival, and multivariable analysis indicated the repair of TAPVC before BDG as the only risk factor (P = 0.032). Whereas the occurrence of postoperative PVS did not reduce survival, which had a significant negative impact on achieving the Fontan operation (P = 0.008). The cumulative survival rate did not improve by surgical era. CONCLUSIONS Surgical outcomes of patients with functional single ventricle undergoing the repair of extracardiac TAPVC in the neonatal period due to obstruction of the venous drainage pathway remain poor. Stent implantation for obstructive drainage veins to delay the timing of surgical correction and sutureless marsupialization as relief of postoperative PVS are expected to improve the late outcomes; however, the effect is still limited.

Long-Term Results of Mitral Valve Repair for Severe Mitral Regurgitation in Infants: Fate of Artificial Chordae

BACKGROUND The experience with mitral valve repair for severe mitral regurgitation in infants was retrospectively reviewed. METHODS From 1978 to 2009, 15 infant patients (4 boys, 7.2±3.2 months old) underwent mitral valve repair for severe mitral regurgitation. The etiology of mitral regurgitation according to Carpentier classification was type I in 1 patient, type II in 10 patients, and type III in 4 patients. Artificial chordal replacement was performed in 11 patients. The follow-up course was completed in all patients, with a median follow-up period of 10.2 years (range, 2.2 to 33.4 years). RESULTS There were no operative or in-hospital mortalities. The actuarial survival and freedom from reoperation rates at 10 years were 89% and 65%, respectively. Five patients required redo mitral valve surgery, including 4 patients needing mitral valve replacement. Three of 4 patients with type III mitral regurgitation, caused by congenital subvalvar structural abnormality, required redo mitral valve surgery. In 11 patients who underwent artificial chordal reconstruction, 2 (18%) required mitral valve replacement during the early postoperative period, whereas the remaining patients showed no recurrent mitral regurgitation during the entire study period. The latest echocardiography findings at 7.3 years after the operation showed that the left ventricular diastolic diameter, mitral valve diameter, and ejection fraction were 99.2%±5.0% of normal, 101.7%±13.3% of normal, and 0.741±0.058, respectively. CONCLUSIONS Long-term durability of mitral valve repair for severe mitral regurgitation in infants was satisfactory. Artificial chordal reconstruction is an effective procedure without an elevated risk of late reoperation.

Long-term outcomes of common atrioventricular valve plasty in patients with functional single ventricle

OBJECTIVES Common atrioventricular valve (CAVV) regurgitation is widely known as a risk factor for mortality and Fontan completion in patients with functional single ventricle. Hence, we reviewed our surgical experience with CAVV plasty in Fontan candidates. METHODS Staged Fontan strategy and extracardiac total cavopulmonary connection as Fontan modification were our principal approaches in 1995. Since then, 38 consecutive Fontan candidates (21 males, median weight at operation was 7.0 kg and median age was 17 months old) underwent CAVV plasty. Right atrial isomerism was associated with 24 patients. The initial CAVV plasty was performed before inter-stage bidirectional Glenn (BDG) in 3 patients, at BDG in 23, before Fontan in 4 and during Fontan in 8. Since 1995, the modified Alfieri technique with a tailed, expanded, polytetrafluoroethylene tube as a bridging strip was the procedure for repair and 27 patients underwent the procedure. The mean follow-up period was 7.1 years (range 0-17 years). RESULTS Actuarial survival and freedom from CAVV replacement rates at 1, 5 and 10 years were 81, 70 and 67% and 89, 85 and 75%, respectively. Seven patients ultimately underwent CAVV replacement with one death. Twenty-three of the 38 patients completed Fontan operation (61%). Association with total anomalous pulmonary venous connection (P= 0.01) and CAVV plasty before BDG (P= 0.05) were risk factors for mortality. CONCLUSIONS CAVV plasty for patients with functional single ventricle is still challenging; however, the aggressive and repeated surgical intervention may contribute to provide better life-prognosis. The ventricular volume unloading effect of BDG without additional pulmonary blood flow or Fontan operation did not contribute to maintain CAVV function. Therefore, there would not be any hesitation for CAVV replacement to control CAVVR in the setting of systemic ventricular failure. Although the statistically significant therapeutic superiority of the modified Alfieri technique was not shown so far, further follow-up may reveal the advantage of this easy and simple technique.

Clinical outcomes of prophylactic Damus-Kaye-Stansel anastomosis concomitant with bidirectional Glenn procedure.

OBJECTIVE We evaluated prophylactic Damus-Kaye-Stansel (DKS) anastomosis in association with the timing of a bidirectional Glenn (BDG) procedure as second-stage palliation aiming at Fontan completion to prevent late systemic ventricular outflow tract obstruction. METHODS Between 1996 and 2005, 25 patients (14 boys; median age, 12 months) underwent a BDG procedure concomitant with DKS anastomosis. All had a systemic ventricular outflow tract through an intraventricular communication or morphologically developed subaortic conus and had previously undergone pulmonary artery banding. Enlargement of intraventricular communication and/or resection of a subaortic conus were not performed before or during the operation. RESULTS Twenty-one (84%) patients subsequently underwent a Fontan operation, with a follow-up period of 6.8 ± 1.9 years (range, 4-11 years), with no mortalities after the Fontan operation. Cardiac catheterization showed that systemic ventricular end-diastolic volume was significantly decreased from 187% ± 74% of normal before BDG to 139% ± 35% after (P = .038) and to 73% ± 14% at 4.3 years after the Fontan operation (P < .001). However, the pressure gradient across the systemic ventricular outflow tract remained at 0.5 ± 0.8 mm Hg after DKS anastomosis and 0.6 ± 2.3 mm Hg at 4.6 years after the Fontan operation. None of the patients showed more than moderate aortic or neoaortic regurgitation, except 1 who progressed to pulmonary regurgitation after DKS anastomosis and required a reoperation for a systemic ventricular outflow tract. No anatomic properties affected late neoaortic valve function. CONCLUSIONS Regardless of a significant reduction in systemic ventricular volume, DKS anastomosis concomitant with a BDG procedure shows promise for a nonobstructive systemic ventricular outflow tract after a Fontan operation.

Tissue-engineered stent-graft integrates with aortic wall by recruiting host tissue into graft scaffold

OBJECTIVE To prevent postoperative migration and endoleaks after endovascular aneurysm repair, we developed a tissue-engineered vascular graft that integrates with the aortic wall by recruiting the host tissue into the graft scaffold. In the present study, we assessed the mechanical properties of the new graft and evaluated the integration between the graft and aortic wall histologically and mechanically in canine models. METHODS The tissue-engineered vascular graft was woven to be partially degradable with a double-layered fiber (core; polyethylene terephthalate [PET], and sheath; polyglycolic acid [PGA]). The mechanical properties of the graft were assessed compared with a thin-walled woven polyester graft (control; 12 mm in diameter, 30 mm long). The stent-grafts, composed of a stainless Z stent (20 mm in diameter, 25 mm long) and a PET/PGA or control graft (n=5 in each group), were implanted in the descending thoracic aorta of mongrel dogs for 2 months. We assessed the histologic findings of the explants and the degree of adhesion between the graft and aortic wall. RESULTS The PET/PGA graft achieved nearly the same mechanical properties as those of the control graft in tensile strength and flexibility, with slightly greater water permeability. At 2 months after implantation, in the PET/PGA group, the PGA component had degraded and been replaced by host tissue that contained a mixture of α-smooth muscle actin-positive cells and other host cells. The graft was a unified structure with the aorta. The adhesion strength between the graft and aortic wall was significantly enhanced in the PET/PGA group. CONCLUSIONS The PET/PGA stent-graft demonstrated histologic and mechanical integration with the native aorta. This next-generation stent-graft might reduce the risk of migration and endoleaks, leading to preferable long-term results of endovascular aneurysm repair.