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.

[Tetralogy of Fallow with Total Anomalous Pulmonary Vein Return and Atrial Septal Defect;Successful Two-staged Surgical Management;Report of a Case].

A combination of tetralogy of Fallot( TOF) and total anomalous pulmonary venous return(TAPVR) is rare and results in chronic volume and pressure load of the right side of the heart and underfilling of the left heart. We report a successful 2-staged surgical correction of TOF associated with TAPVR and atrial septal defect. The patient was unsuitable for total primary intracardiac correction because the volume of the left ventricle was considered to be small. First, repair of anomalous pulmonary venous return and palliative right ventricle outflow tract reconstruction were simultaneously performed in 2 months of birth. One year after 1st operation, cardiac catheterization revealed that normalization of left ventricle volume, so 2nd operation was planned. Total correction of ventricular septal defect and right ventricle outflow reconstruction was performed and the patient was discharged on the 21st postoperative day with good hemodynamic status.

Severe aortic insufficiency due to a huge leaflet perforation in Libman-Sacks syndrome: report of a case.

A 40-year-old woman who was diagnosed to have systemic lupus erythematosus developed complications of cerebral infarction and alveolar hemorrhage. Close examination revealed severe aortic insufficiency, and she was diagnosed with Libman-Sacks syndrome. Due to progressive dilatation of the left ventricle and her easily fatigued state, surgery was performed. On pathological examination, holes of 4-mm and 5-mm diameter were detected in the left coronary and noncoronary cusps of the aortic valve, respectively. The morphology of the valve lesions showed a characteristic shape of such huge holes.

Effect of a miniaturized cardiopulmonary bypass system on the inflammatory response and cardiac function in neonatal piglets.

The cognitive impairment and hemodynamic instability after neonatal cardiac surgery with cardiopulmonary bypass (CPB) might be exacerbated by hemodilution. Therefore, this study investigated the impact of different bloodless prime volumes on the hemodynamics and the inflammatory response by a miniaturized CPB system in neonatal piglets. The bypass circuit consisted of a Capiox RX05 (Capiox Baby RX, Terumo Corp., Tokyo, Japan) oxygenator and 3/16 internal diameter arterial and venous polyvinyl chloride tubing lines, with a minimum 75 mL prime volume. Twelve 1-week-old piglets were placed on a mild hypothermic CPB (32 degrees C) at 120 mL/kg/min for 2 h. The animals were divided into two groups, based on the volume of the prime solution. The priming volume was 75 mL in Group I and 175 mL in Group II. No blood transfusions were performed, and no inotropic or vasoactive drugs were used. The interleukin-6 (IL-6) and thrombin-antithrombin (TAT) complex levels, as well as right ventricular and pulmonary functions, were measured before and after CPB. Group I had low levels of IL-6 and TAT immediately after CPB (4370 +/- 2346 vs. 9058 +/- 2307 pg/mL, P < 0.01 and 9.9 +/- 7.7 vs. 25.1 +/- 8.8 ng/mL, P < 0.01, respectively). Group I had significantly improved cardiopulmonary function, cardiac index (0.22 +/- 0.03 vs. 0.11 +/- 0.05 L/kg/min, P < 0.001), and pulmonary vascular resistance index (7366 +/- 2860 vs. 28 620 +/- 15 552 dynes/cm(5)/kg, P < 0.01) compared with Group II. The miniaturized bloodless prime circuit for neonatal CPB demonstrated that the influence of hemodilution can reduce the subsequent inflammatory response. In addition, a low prime volume could therefore be particularly effective for attenuating pulmonary vascular resistance and right ventricular dysfunction in neonates.

Surgical Repair for the Treatment of Pulmonary Vein Stenosis After Radiofrequency Ablation.

Radiofrequency ablation procedures for atrial fibrillation are occasionally associated with pulmonary vein stenosis (PVS). A common treatment for PVS is catheter intervention; however, because of the high restenosis rate, it is not suitable for young patients. The case presented herein is of a young male patient with severe bilateral PVS who underwent successful surgical pulmonary vein repair by sutureless technique. The stenotic lesions of the pulmonary veins were dissected and were covered using autologous pericardium. An enhanced computed tomographic scan revealed that all the pulmonary veins were widely patent after 6 months from the operation.

Repair of a dysplastic tricuspid valve using artificial chordae: case report.

Atrioventricular valve repair with artificial chordal replacement has been widely used for congenital and acquired mitral valve abnormalities, but not for tricuspid valve abnormalities. A case is presented of dysplastic tricuspid valve that was successfully repaired using artificial chordae. A 2-year-old female presented with poor weight gain. Echocardiography revealed severe tricuspid regurgitation due to dysplastic tricuspid valve, poor coaptation by prolapse of the anterior leaflet, and tethering of the septal leaflet by short chordae. The prolapsed anterior leaflet was repaired with three pairs of 6-0 expanded polytetrafluoroethylene sutures. The short chordae of the septal leaflet were detached, and the septal and posterior leaflets were sutured together. Trivial tricuspid regurgitation was noted postoperatively. There was no tricuspid regurgitation during the follow up period of three years. The present case provides further evidence that artificial chordal replacement is a useful technique even for small children with congenitally abnormal tricuspid valves.

Continuous cerebral and myocardial perfusion during aortic arch repair in neonates and infants.

To minimize myocardial ischemia, we repaired aortic arch obstruction with ventricular septal defect, using two different techniques of cerebral and myocardial perfusion. Seventy-one infants, ages 3 to 137 days, underwent primary repair of coarctation of the aorta (n = 49)/interruption of the aortic arch (n = 22) with ventricular septal defect. In 65 patients, an end-to-end arch anastomosis was performed with cerebral and myocardial perfusion through the innominate or the ascending arterial cannula (non-working beating heart: NWBH). In the remaining 6 patients, an arterial cannula was placed into the innominate artery. With partial cardiopulmonary bypass, the innominate artery was snared proximal to the cannulation site and the ascending aorta was cross-clamped. An extended arch anastomosis was carried out with cerebral perfusion and a working beating heart (WBH). Ten patients (15%) undergoing aortic arch repair with the NWBH technique required cardioplegic arrest to complete a proximal anastomosis, whereas in all 6 repairs with the WBH technique, the extended anastomoses were completed without myocardial ischemia. One hospital death and late death occurred, with an overall survival of 98%. End-to-end arch reconstruction is feasible without myocardial ischemia, using the NWBH technique in patients without hypoplastic arch and using the WBH technique in patients with hypoplastic arch.

Advantages of temporary venoatrial shunt using centrifugal pump during bidirectional cavopulmonary shunt.

Single-ventricle palliation without the use of cardiopulmonary bypass carries advantages that reduce systemic edema and inflammatory responses; however, simple clamping of the superior vena cava (SVC) without a temporary shunt leads to increase in cerebral venous pressure and subsequent decrease in cerebral blood flow during bidirectional cavopulmonary shunt (BCPS). We report our experience of BCPS, using a centrifugal pump-assisted temporary shunt. The criteria included an unrestrictive interatrial communication, the absence of atrioventricular valve regurgitation, and the existence of an antegrade pulmonary blood flow. From August 2000, 14 children with single-ventricle physiology met the criteria. The mean age was 1.0 +/- 0.9 years, and the mean weight was 8.4 +/- 2.6 kg. A temporary shunt was established between the SVC and the right atrium with right-angle cannulae, which were connected to a centrifugal pump to accelerate the blood flow from the SVC to the right atrium. All patients tolerated the procedure. Mean central venous pressure was 17 +/- 4 mm Hg, and transcutaneous oxygen saturation was maintained at 77 +/- 8% during anastomosis. No patients required blood transfusion. There were no postoperative neurological complications. The centrifugal pump-assisted temporary shunt offered safer and more effective circulatory support than other shunt systems, with excellent venous drainage in pediatric patients undergoing BCPS.

Mid-term results of open aortic valvotomy for infants with critical aortic stenosis: seven-year experience including delayed Ross strategy.

OBJECTIVES: The purpose of this study is to provide short- and mid-term results of open aortic valvotomy (OAV) for patients with critical aortic stenosis (AS). METHODS: Between December 1993 and June 1996, 6 patients with critical AS underwent an OAV in our unit. Their ages and body weights at operation ranged from 1 to 65 days (median age, 9 days) and from 2.4 to 5.7 kg (median weight, 3.3 kg), respectively. Peak pressure gradient and diameter of the aortic valve ranged from 25 to 111 mmHg (mean value, 79 mmHg) and from 4.6 to 7.5 mm (mean diameter, 6.1 mm), respectively. OAV comprised the valvular commissurotomy and excision of the myxomatous nodules with cardiopulmonary bypass. RESULTS: No early or late death occurred. Mean peak pressure gradient across the aortic valve was reduced to 33 mmHg (from 15 to 44 mmHg) with no aortic insufficiency in 2 patients and trivial insufficiency in 4. During the follow-up period of 6 to 9 years, 3 out of 6 patients required no reintervention. The other 3 patients required repeated valvotomy for recurrent stenosis within 0.2 to 1.3 years after the operation. Of these, 2 patients required the Ross procedure at 7 years of age or older, and another at 6 years of age awaits the Ross procedure. CONCLUSION: OAV for critical AS was effective without causing mortality or significant aortic insufficiency. Our current strategy comprising the initial OAV and "delayed Ross procedure" for recurrent stenosis with or without insufficiency is a promising therapeutic option for infants with critical AS.

Left Ventricular Myxoma Occluding the Suprarenal Abdominal Aorta in an Infant.

Myxoma is the most common primary cardiac tumor in adults; however, it is extremely rare in infants. Acute occlusion of the abdominal aorta by a cardiac myxoma is also rare. We report the case of an infant with acute occlusion of the suprarenal abdominal aorta by a left ventricular myxoma. The patient underwent successful catheter embolectomy of the abdominal aorta and surgical resection of the cardiac myxoma. This is a very rare case report of the combination of infantile left ventricular myxoma and acute occlusion of the abdominal aorta.

Comparison of limited and full sternotomy in aortic valve replacement.

OBJECTIVE: The practice of minimally invasive valve surgery remains controversial. The aim of this study was to evaluate the technical feasibility and postoperative course of aortic valve replacement through limited upper sternotomy compared to conventional full sternotomy. METHODS: From May 1998 to August 2000, we performed 24 cases of isolated aortic valve replacements through the limited upper sternotomy approach (group M). During the same period, 18 patients received isolated aortic valve replacements through the conventional full sternotomy approach (group C). Operation duration, postoperative course and laboratory data were compared between the two groups. RESULTS: All patients received a valve replacement with a prosthetic valve. There was no significant difference between the two groups in mean aortic cross-clamping time, mean cardiopulmonary bypass time or mean operation duration (skin to skin). No patient required blood transfusion. Patients in the group M were extubated earlier, with less postoperative blood loss and discharged earlier after the operation than those in group C. On the first postoperative day, the peak level of lactic acid dehydrogenease was significantly lower in the group M than those in group C. CONCLUSION: Limited upper sternotomy for aortic valve replacement resulted in shorter operation duration and minimized operative risks for the patients. We believe this method brings not only cosmetic benefits but also improved postoperative course.

[Hypoplastic left heart syndrome].

Hypoplastic left heart syndrome (HLHS) is one of the last remaining problems in pediatric cardiac surgery, which necessitates a search for new solutions and continues to be a challenge for cardiologists and cardiac surgeons. The identification of HLHS in utero is extremely helpful for prompt, appropriate preoperative management. In addition, infants with prenatal diagnosis had an improvement operative mortality on Norwood operation compared to infants diagnosed postnatally. Outcome following Norwood procedure has improved significantly secondary to modifications in the surgical technique for protection of multiorgans, improved perioperative care, and improved anesthetic management. In particular right ventricular (RV)-pulmonary artery (PA) shunt using non-valved polytetrafluoroethylene (PTFE) graft was applied as a first stage palliation of HLHS to prevent hemodynamic instability associated with a classic Norwood procedure. In the modified Norwood (RV-PA shunt), higher diastolic blood pressures and lower Qp/Qs ratios that are associated with a more stable and efficient systemic circulation. In fact, patients who received a RV-PA shunt, rarely received ventilatory manipulations.

Repair of Ebstein's anomaly in neonates and small infants: impact of right ventricular exclusion and its indications.

OBJECTIVES: In cases of severe Ebstein's anomaly, it is essential to determine whether biventricular repair (BVR) or single-ventricle palliation is feasible. Since 1999, in our institution, we have used the novel technique comprising tricuspid valve (TV) closure and right ventricular and right atrial (RV/RA) exclusion to reduce the deleterious effects of an enlarged RV in patients with severe Ebstein's anomaly. However, in cases with good RV function, primary BVR is performed. In the present study, we describe our surgical strategy in the treatment of severely symptomatic neonates with Ebstein's anomaly. METHODS: From June 1999 to October 2011, 12 neonates with a severely symptomatic Ebstein's anomaly underwent surgical repair. The mean age at the first operation was 29 ± 25 (range, 5-92) days; and the mean body weight was 2.8 ± 0.5 (range, 2.0-4.1) kg. The associated anomalies included pulmonary atresia with an intact ventricular septum in 7, critical pulmonary stenosis in 1, ventricular septal defect in 3 and coarctation of the aorta in 1 patient. The mean cardio-thoracic ratio (CTR) was 80 ± 14% (range, 57-98%). Preoperatively, 9 patients had grade IV tricuspid regurgitation (TR), as detected by echocardiography, and 6 required ventilator support. RESULTS: Five patients underwent primary BVR. Seven patients underwent staged palliation using a modified Blalock-Taussig shunt (BT shunt) with/without RV/RA exclusion. There was 1 case each of hospital death and late death. The median follow-up duration in the present study was 6.5 years. Among the 8 patients who underwent TV repair, postoperative TR was trivial or mild in 6 patients, moderate in 1 and absent in 1. After surgery, the mean CTR and serum B-type natriuretic peptide levels decreased to 59 ± 14% (range, 45-70%) and 46 ± 28 (range, 12-83) pg/dl, respectively. CONCLUSIONS: Critically ill neonates with Ebstein's anomaly can be successfully treated using RV/RA exclusion combined with a modified BT shunt in cases where RV function is poor. However, in cases of good RV function, we recommend the use of primary BVR.

The effect of pulmonary root translocation on the left ventricular outflow tract.

We report the effect of pulmonary root translocation on the left ventricular outflow tract. A double switch operation with pulmonary root translocation was performed in a 6-year-old boy whose diagnosis was dextrocardia, congenitally corrected transposition of the great arteries, ventricular septal defect, and pulmonary stenosis. Postoperative magnetic resonance imaging showed more natural left ventricular outflow than preoperatively (19 mm vs 22 mm in length between the top of the interventricular septum and the aortic valve). This technique does not require coronary transfer and enables preservation of the aortic root structure. The long-term results, including left ventricular outflow tract morphology, should be evaluated.

Apico-brachiocephalic artery bypass for aortic stenosis with porcelain aorta.

Apicoaortic bypass for left ventricular outflow tract obstruction has been performed with acceptable mid-term mortality. However, sometimes it is difficult to anastomose the distal end of the conduit to the calcified descending aorta in patients with a porcelain aorta. We report an aortic non-touch modification of the apicoaortic bypass in an 80-year-old woman with valvular aortic stenosis and a porcelain aorta extending from the ascending to abdominal aorta. We performed apico-brachiocephalic artery bypass under circulatory arrest with deep hypothermia. This procedure may become a useful surgical option for patients with a severe porcelain aorta.

Minimally invasive cardiac surgery for a young woman with Marfan syndrome and mitral regurgitation.

The case involved a 26-year-old woman with Marfan syndrome (MFS) and severe mitral valve regurgitation who hoped to bear a child. Anticipating future surgery to treat cardiovascular disease via a median sternotomy, we performed mitral annuloplasty via a right anterior thoracotomy. Mitral valve repair for mitral valve regurgitation via a right anterior thoracotomy is one of the most beneficial procedures for patients with MFS.

Ultrafiltration of priming blood before cardiopulmonary bypass attenuates inflammatory response and maintains cardiopulmonary function in neonatal piglets.

Blood priming is necessary for cardiopulmonary bypass (CPB) in neonates to avoid excessive hemodilution; however, transfusion-related inflammation affects postCPB outcomes in neonatal open-heart surgery. We hypothesized that ultrafiltration of priming blood before CPB may reduce inflammatory mediators in priming blood and postCPB inflammatory responses, thereby improving cardiopulmonary function. Twelve 1-week-old piglets (3.5 +/- 0.2 kg) were divided into two groups. Group U (n = 6) employed the priming blood ultrafiltrated before CPB, but group N (n = 6) used the nonultrafiltrated blood. Cardiopulmonary bypass was performed for 2 hours and then modified ultrafiltration (MUF) was conducted. Data were acquired before CPB and after MUF. The values of K+, serotonin, and IL-8 in priming blood was significantly decreased after ultrafiltration (8.2 +/- 2.6 vs. 4.2 +/- 0.8 mEq/L, p < 0.01, 234 +/- 96 vs. 74 +/- 42 ng/ml, p < 0.01, 78.4 +/- 5.1 vs. 64.5 +/- 59.1 pg/ml, p < 0.05). Group U after MUF had lower thrombin-antithrombin complex levels (23.9 +/- 5.1 vs. 33.7 +/- 4.6 ng/ml, p < 0.01) and lower IL-8 levels in airway fluid (925 +/- 710 vs. 2495 +/- 1207 pg/ml, p < 0.05) than group N. Cardiac output and arterial PO2 after MUF in group U were also higher (1.13 +/- 0.21 vs. 0.69 +/- 0.22, p < 0.01, 340 +/- 190 vs. 149 +/- 84 mm Hg, p < 0.05). The ultrafiltration of blood priming before CPB attenuated activation of the coagulation pathway and inflammatory responses and preserved cardiopulmonary function in neonatal piglets.