Yasuhiro Kotani

Risk Factors for Mortality After the Norwood Procedure Using Right Ventricle to Pulmonary Artery Shunt

BACKGROUND The purpose of this study was to describe the experience with staged surgical reconstruction of the hypoplastic left heart syndrome (HLHS) with a right ventricle to pulmonary artery conduit and to identify the risk factors that influence late outcome. METHODS Between February 1998 and June 2007, 62 patients with HLHS underwent a Norwood procedure by using right ventricle to pulmonary artery conduit (median age, 9 days [range, 1 to 57]; median body weight 2.7 kg [range, 1.6 to 3.9 kg]). The subsequent 47 patients underwent a bidirectional Glenn procedure (stage 2). Thirty-two patients underwent a modified Fontan procedure (stage 3). Follow-up was complete (median, 32 months; range, 1 to 101). RESULTS Hospital mortality after the Norwood procedure was 8% (5 of 62 patients). Between stages, 9 patients died, 3 before stage 2 and 6 before stage 3. There was 1 late death after stage 3. Overall survival was 76% (47 of 62). The estimated 1-year and and 5-year survival rates were 80% and 73%, respectively. Using the any-mortality as the endpoint, prematurity (gestational age <37 weeks), body weight less than 2.5 kg at stage 1 operation, and tricuspid regurgitation 2+ or more were associated with mortality. Using Cox regression analysis, body weight less than 2.5 kg and tricuspid regurgitation 2+ or more were two independent factors associated with midterm survival. CONCLUSIONS From 9 years of experience, despite good early survival after Norwood stage 1 palliation, low body weight and tricuspid valve regurgitation were still associated with worse outcome. More efforts should be made to improve the late results for patients with hypoplastic left heart syndrome.

Hybrid Versus Norwood Strategies for Single-Ventricle Palliation

Background— Hybrid and Norwood strategies differ substantially in terms of stage II palliative procedures. We sought to compare these strategies with an emphasis on survival and reintervention after stage II and subsequent Fontan completion. Methods and Results— Of 110 neonates with functionally single-ventricle physiology who underwent stage I palliation between 2004 and 2010, 75 (69%) infants (Norwood, n=43; hybrid, n=32) who subsequently underwent stage II palliation were studied. Survival and reintervention rates after stage II palliation, anatomic and physiologic variables at pre-Fontan assessment, and Fontan outcomes were compared between the groups. Predictors for reintervention were analyzed. Freedom from death/transplant after stage II palliation was equivalent between the groups (Norwood, 80.4% versus hybrid, 85.6% at 3 years, P=0.66). Hybrid patients had a higher pulmonary artery (PA) reintervention rate (P=0.003) and lower Nakata index at pre-Fontan evaluation (P=0.015). Aortic arch and atrioventricular valve reinterventions were not different between the groups. Ventricular end-diastolic pressure, mean PA pressure, and ventricular function were equivalent at pre-Fontan assessment. There were no deaths after Fontan completion in either group (Norwood, n=25, hybrid, n=14). Conclusions— Survival after stage II palliation and subsequent Fontan completion is equivalent between the groups. The hybrid group had a higher PA reintervention rate and smaller PA size. Both strategies achieved adequate physiology for Fontan completion. Evolution of the hybrid strategy requires refinement to provide optimal PA growth.

Left Atrial Decompression During Venoarterial Extracorporeal Membrane Oxygenation for Left Ventricular Failure in Children: Current Strategy and Clinical Outcomes

From 2005 to 2011, 23 of 178 (12.9%) patients with venoarterial (VA) extracorporeal membrane oxygenation (ECMO) had left atrial (LA) decompression to help improve left ventricular (LV) function, LA/LV dilatation, and/or lung edema. LA decompression was achieved with LA cannulation (n = 16), surgically created adjustable atrial septal defect (n = 3), or balloon atrial septostomy (n = 4). Sixteen (70%) patients had LA decompression at the time of ECMO initiation and all had LA decompression within 12 hours of ECMO initiation. ECMO duration was 5.9 ± 4.5 days and 16 (70%) patients were successfully decannulated. Subsequent intensive care unit and hospital survival was achieved in 13 (57%) and 12 (52%) patients, respectively. Earlier timing of LA decompression appeared to be associated with a high probability of weaning from ECMO and reasonable LV functional recovery.

Surgical Palliation Strategy Does Not Affect Interstage Ventricular Dysfunction or Atrioventricular Valve Regurgitation in Children With Hypoplastic Left Heart Syndrome and Variants

Background— All 3 palliation strategies, Norwood, Sano, and Hybrid, currently used for hypoplastic left heart syndrome pose a risk of myocardial injury at different times and through different mechanisms. We sought to compare these strategies to understand longitudinal differences in interstage ventricular dysfunction and their subsequent impact on transplant-free survival and atrioventricular valve regurgitation (AVVR) as well as the relationship between adverse events and ventricular function. Methods and Results— Serial echocardiographic reports and clinical data were reviewed for 138 children with hypoplastic left heart syndrome who underwent stage I surgical palliation (Sano: 11; Norwood: 73; Hybrid: 54) between 2004 and 2011. Stage II palliation was achieved in 92 (67%) patients (Sano: 7; Norwood: 51; Hybrid: 34). Interstage transplant-free survival, ventricular dysfunction, and AVVR were equivalent among palliation strategies. Patients with preserved ventricular function had a higher rate of transplant-free survival and freedom from AVVR, regardless of palliation strategy. Patients who had cardiac arrest, cardiopulmonary resuscitation, or extracorporeal membrane oxygenation (adverse events) experienced more transient and persistent ventricular dysfunction compared to those without adverse events. Surgical palliation strategies were not identified as risk factors for ventricular dysfunction or AVVR. Conclusions— Surgical palliation strategy does not affect mortality, interstage ventricular function, or interstage AVVR in children with hypoplastic left heart syndrome. Therefore, the different timing and mechanisms of myocardial injury among palliation strategies do not affect outcomes. Ventricular dysfunction adversely affects transplant-free survival and atrioventricular valve function. Adverse events are associated with the development of ventricular dysfunction. To improve outcomes, interstage treatment should focus on the preservation of ventricular function.

Midterm to Long-Term Outcome of Total Cavopulmonary Connection in High-Risk Adult Candidates

BACKGROUND Adult patients who do not fulfill the classical Fontan criteria now undergo total cavopulmonary connection (TCPC). However, limited information is available on the results for high-risk adult TCPC. METHODS Twenty-five consecutive adult patients (aged 16 years or more) who underwent TCPC were retrospectively reviewed. The mean age at operation was 27 +/- 9 years (range, 16 to 52). The following items were considered as the potential risk factors according to previous reports: (1) aged more than 30 years (7 of 25); (2) heterotaxy (9 of 25); (3) systemic ventricular ejection fraction less than 50% (6 of 25); (4) atrioventricular valve regurgitation moderate or greater (6 of 25); (5) pulmonary arterial index less than 200 (7 of 25); (6) mean pulmonary arterial pressure 15 mm Hg or greater (3 of 25); (7) pulmonary arterial resistance 2.0 wood units or greater (11 of 25); (8) arrhythmias (13 of 25); (9) protein-losing enteropathy (3 of 25); (10) New York Heart Association (NYHA) functional class III or greater (9 of 25); (11) previous Fontan procedure (10 of 25); (12) systemic ventricular outflow obstruction (1 of 25); and (13) end-diastolic pressure of the systemic ventricle 11 mm Hg or higher (4 of 25). RESULTS The mean follow-up period was 57 +/- 45 months (range, 0 to 154). All patients had at least 2 risk factors (range, 2 to 8). There was 1 early death and 2 late deaths. Comparing the late survivors and nonsurvivors, no statistical significance was identified in the above risk factors. However, the patients with 6 or more risk factors had a significantly higher mortality rate than patients with fewer than 6 risk risk factors (p < 0.01). Age (p = 0.08), NYHA class (p = 0.13), and protein-losing enteropathy (p = 0.08) may be risk factors for late death. CONCLUSIONS The majority of the adult TCPC candidates tolerated the TCPC procedure in the early postoperative period. However, the accumulation of risk factors influences late mortality.

Clinical outcome of the Fontan operation in patients with impaired ventricular function

OBJECTIVE Although a staged Fontan strategy allows for an excellent outcome in high-risk patients, an impaired ventricular function remains a significant factor of early/late mortality and morbidity. This study evaluated the clinical outcome of the Fontan operation in patients with impaired ventricular function. METHODS A retrospective review was performed on 217 patients who had undergone the Fontan operation between 1991 and 2007. RESULTS Twenty-nine (13%) of the 217 patients had an impaired ventricular function (ejection fraction (EF) <50%). The median age at the time of the operation was 3 (range: 1-31 years) years. There were five adult patients. The ventricular morphology was right in 20 patients (including five hypoplastic left heart syndrome (HLHS)) and others (left and two-ventricle) in nine patients. Heterotaxy syndrome was present in eight patients. Previous surgical interventions included bidirectional Glenn anastomoses in 24, modified Blalock-Taussig shunts in two and pulmonary artery banding in two. The preoperative EF was 43+/-6%. Significant (moderate or severe) atrioventricular valve regurgitation was noted in four patients. The percutaneous oxygen saturation (SpO(2)) was 82+/-5%. The pulmonary artery pressure and pulmonary artery index were 11+/-3 mmHg and 296+/-102 mm(2)m(-2), respectively. All 29 patients underwent the Fontan operation without any early mortality. There were two late mortalities and two re-operations. EF was maintained at 59+/-15% at a median follow-up of 7.5 (range: 1-19) years. The percent normal systemic ventricular end-diastolic volume decreased from 174+/-95% to 124+/-39% (p<0.05). The SpO(2) increased to 92+/-2%. The mean cardiothoracic ratio in chest X-ray and B-type natriuretic peptide were 51% (range: 35-68%) and 22 pgml(-1) (range: 9-382 pgml(-1)), respectively. Three patients developed congestive heart failure, seven had arrhythmia and two developed protein-losing enteropathy. The New York Heart Association (NYHA) class functional class is I in 21 patients, II in five and III in one. CONCLUSIONS Acceptable clinical outcomes were observed at an intermediate follow-up of the Fontan operation in patients with an impaired ventricular function.

Single center experience with a low volume priming cardiopulmonary bypass circuit for preventing blood transfusion in infants and small children.

This retrospective study analyzed the current practice of blood transfusion-free open-heart surgery in 536 children weighing 5–20 kg undergoing surgery between 2004 and 2007. A miniaturized cardiopulmonary bypass (CPB) circuit was used (priming volume; 300 ml for the flow rate <1,500 ml/min; 550 ml for the flow rate of 1500–2300 ml/min). Modified ultrafiltration was routinely performed. Criteria for blood transfusion during CPB included a hematocrit of <20% and/or mixed venous oxygen saturation of <65%. Transfusion during CPB was avoided in 264 (49.3%) of the 536 patients (5–10 kg group, 29.0%; 11–15 kg group, 67.4%; 16–20 kg group, 80.8%). There was no neurological complication related to hemodilution. Multiple logistic regression analysis revealed that body weight, preoperative hematocrit, priming volume of CPB circuit, CPB time, and lowest hematocrit during CPB predict requirement of blood transfusion (p < 0.01). Transfusion rate was lowest in the atrial septal defect group (5.6%) and highest in tetralogy of Fallot group (78.7%), being associated with complexity of diagnosis and procedure required. Blood transfusion-free open-heart surgery may be achieved in the half of the patients weighing 5–20 kg, and further miniaturization of CPB circuit and refinement of perfusion strategy might reduce transfusion rate in patients <10 kg and/or with complex congenital heart disease.

Circulatory Load During Hypoxia Impairs Post-transplant Myocardial Functional Recovery in Donation After Cardiac Death

BACKGROUND Circulatory load during hypoxia is unavoidable in donation after cardiac death (DCD) hearts, but it causes severe myocardial damage. The impact of circulatory load on donor heart function has not been investigated. The purpose of this study was to evaluate its effect on post-transplant functional recovery of DCD hearts. METHODS Twelve donor pigs (20 kg) were used. Cardiac arrest was induced by asphyxiation (turning off the ventilator) in the load group (n = 6) and by exsanguination (dividing the vena cava) in the unload group (n = 6). Left ventricle end-diastolic volume (LDEDV) and end-systolic pressure (LVESP) were monitored until cardiac arrest. Orthotopic transplantation was performed after 30-minute warm ischemia following cardiac arrest. After weaning from cardiopulmonary bypass, left ventricular end-diastolic pressure-volume ratio (LV Emax) and creatine kinase (CK-MB) were measured while on 0.1 microg/kg/min epinephrine. RESULTS During the agonal period, the maximum LVEDV and LVESP in the load group were 132 +/- 1% of baseline at 10 minutes and 148 +/- 16% of baseline at 4 minutes, respectively. Recovery rates of post-transplant cardiac function in the load group were worse than in the unload group (LV Emax: 64 +/- 8 vs 84 +/- 5%, p < 0.05). Levels of post-transplant CK-MB in the load group were higher than in the unload group (639 +/- 119 vs 308 +/- 70 IU/liter, p < 0.05). CONCLUSIONS Cardiac arrest with circulatory load by asphyxiation caused more myocardial damage than unloaded arrest. This difference between the modes of death should be considered when evaluating the DCD hearts for clinical application.

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.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 cardiosphere-derived cells (CDCs) may be effective against congenital heart failure. Objective: To determine if 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 41 patients in a 1:1 ratio who had single ventricle physiology undergoing staged-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 cardiac function improvement at 3-month follow-up. Four months after palliation, controls had an alternative option to receive late CDC-infusion upon request (study B). Secondary outcomes included ventricular function, heart failure status, somatic growth, and health-related quality of life (QOL) after a 12-month observation. At 3 months, the absolute changes in ventricular function were significantly greater in the CDC-treated group than in controls (+6.4% [SD 5.5] vs. +1.3% [3.7]; P=0.003). In study B, a late CDC-infusion in 17 controls increased the ventricular function at 3 months compared with baseline (38.8% [SD 7.7] vs. 34.8% [7.4]; P<0.0001). At 1 year, overall CDC infusion was associated with improved ventricular function (41.4% [SD 6.6] vs. 35.0% [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 QOL, 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 QOL in patients, and reduce parenting stress for their families. Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT01829750.

The potential of disproportionate growth of tricuspid valve after decompression of the right ventricle in patients with pulmonary atresia and intact ventricular septa

OBJECTIVE Tricuspid valve size is the major determinant of outcomes for patients with pulmonary atresia with intact ventricular septum. Lack of right ventricle-pulmonary artery continuity is associated with poor tricuspid valve growth (decrement in Z-value). However, most reports did not show evidence for disproportionate growth of the tricuspid valve after establishment of right ventricle-pulmonary artery continuity. METHODS We studied 40 patients with pulmonary atresia with intact ventricular septum who underwent initial right ventricular decompression for planned staged repair. The initial Z-value of the tricuspid valve diameter (Zt1) was obtained from the echocardiography-derived normal value. The late Z-value (Zt2) was measured before definitive repair or the last available Z-value, if definitive repair was not yet reached. The factors associated with the changes of Z-values (Zt2 - Zt1) were analyzed. RESULTS The mean initial tricuspid Z-value (Zt1) was -6.2 +/- 3.5. After treatment (Zt2), the mean Z-value was -6.0 +/- 3.4 (n = 34). Overall, the tricuspid Z-values did not change. Individually, the change in Z-value (Zt2 - Zt1) was larger than +2 in 11 (32%) patients and smaller than -2 in 6 (18%) patients. Increases in Z-value (Zt2 - Zt1) were significantly associated with right ventricular pressure/left ventricular pressure ratio measured after initial palliation (r = -0.54; P = .001) and the initial tricuspid valve Z-value (Zt1) (r = -0.40; P = .02). CONCLUSIONS Disproportional growth of the tricuspid valve can occur, especially in patients with small tricuspid valves and lower right ventricular pressures after decompression. The findings support the possibility of neonates with small tricuspid valves undergoing biventricular repair after right ventricular decompression surgery.