Osami Honjo

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.

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

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

Clinical Outcomes, Program Evolution, and Pulmonary Artery Growth in Single Ventricle Palliation Using Hybrid and Norwood Palliative Strategies

BACKGROUND Hybrid strategies for single ventricle palliation may differ from Norwood strategies in terms of anatomic and physiologic growth stimuli to the pulmonary arteries (PA), hemodynamics, resource utilization, and survival. Few studies have directly compared these strategies. METHODS In all, 58 patients underwent Norwood (Blalock-Taussig shunt; n = 39) or hybrid (n = 19) single ventricle palliation (2004 to 2007). Hemodynamics, PA morphology, hemodynamics, resource utilization, and survival were reviewed. RESULTS At pre-stage 2 evaluation, there were nonsignificant trends toward lower ventricular end-diastolic pressure, higher mixed venous saturation, and larger Nakata and lower lobe indices in the hybrids. Mean PA pressures were not different between groups. Four Norwood patients (10%) underwent transplantation before stage 2 palliation. Forty-two patients underwent stage 2 palliation (bidirectional cavopulmonary shunt or stage 2 hybrid (aortic arch reconstruction and bidirectional cavopulmonary shunt). Requirement for PA plasty, postoperative CVP, stage 2 survival, and 1-year survival were similar between groups. Combined (stage 1 plus stage 2) intubation time, intensive care unit time, and hospital length of stay was shorter for hybrids in comparison with Norwood survivors (p < 0.05). Comparison of resource utilization at the time of arch reconstruction (Norwood procedure or stage 2 hybrid), demonstrated a time-related trend toward improvement (weak negative correlation: intubation, rho = -0.386, p = 0.172; intensive care unit stay, rho = -0.487, p = 0.077; hospital stay, rho = -0.429, p = 0.126) in the hybrid group, but not in the Norwood group. CONCLUSIONS Hybrid palliation does not have a significant adverse impact on PA development, with comparable PA growth and hemodynamics. The demonstration of equivalent survival, diminished hospital utilization, and trends indicating ongoing refinement of the hybrid strategy warrants a prospective randomized trial.

Adverse Biventricular Remodeling in Isolated Right Ventricular Hypertension Is Mediated by Increased Transforming Growth Factor–β1 Signaling and Is Abrogated by Angiotensin Receptor Blockade

The pressure-loaded right ventricle (RV) adversely affects left ventricular (LV) function. We recently found that these ventricular-ventricular interactions lead to LV myocardial fibrosis through transforming growth factor-β1 (TGF-β1) signaling. We investigated the mechanisms mediating biventricular fibrosis in RV afterload and their potential modification by angiotensin receptor blockade. An adjustable pulmonary artery band (PAB) was placed in rabbits. In sham-operated control rabbits, the band was left uninflated (n = 6). In the RV afterload group, the PAB was sequentially inflated to generate systemic RV pressure at 28 days (n = 8). In a third group, the PAB was inflated to systemic levels, and the angiotensin receptor blocker losartan was added (n = 6). Five weeks after surgery, the animals were killed for assessments of biventricular hypertrophy, fibrosis, apoptosis, and the components of their signaling pathways. PAB animals developed biventricular hypertrophy, fibrosis, and apoptosis, versus sham rabbits, in which these conditions were decreased with losartan. RV and LV TGF-β1, connective tissue growth factor (CTGF) (CCN2), endothelin-1 (ET-1), endothelin receptor B, and matrix metalloproteinase 2/9 mRNA levels were increased in PAB animals versus sham animals, and decreased with losartan. Given the marked biventricular CTGF up-regulation in PAB and down-regulation with losartan, we investigated CTGF signaling. RV and LV Smad 2/3/4 protein levels and LV RhoA mRNA levels were increased with PAB and reduced with losartan. In conclusion, isolated RV afterload induces biventricular fibrosis and apoptosis, which are reduced by angiotensin receptor blockade. Adverse ventricular-ventricular interactions induced by isolated RV afterload appear to be mediated through TGF-β1-CTGF and ET-1 pathways.

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.

Primary sutureless repair for infants with mixed total anomalous pulmonary venous drainage.

BACKGROUND Mixed type total anomalous pulmonary venous drainage (TAPVD) poses technical challenges and high mortality owing to diminutive size and remote location of the pulmonary vein (PV) confluences. We hypothesized that primary application of sutureless repair may better incorporate small and remote confluences, thereby minimizing PV stenosis and improving outcomes. METHODS Twenty-two consecutive infants (1985 to 2009; median age 27 days; body weight 3.7 kg) with mixed type TAPVD were retrospectively reviewed. Survival and reintervention were compared between the sutureless group (n = 8) and the conventional group (n = 14). Predictors for death and reintervention were identified by an univariate analysis using a chi(2) test. RESULTS No differences were noted on preoperative and intraoperative variables between the groups. There were 5 early deaths in the conventional group and no deaths in the sutureless group (p = 0.05). There were trends toward improved survival (100% versus 57% at 1 year, p = 0.07) and freedom from reintervention (100% versus 67% at 1 year, p = 0.09) in the sutureless group. The univariate analysis showed that preoperative PV obstruction (p = 0.05), conventional repair (p = 0.05), palliative surgery (p = 0.001), and residual PV obstruction (p = 0.002) were the risk factors for death. Preoperative PV obstruction, palliative surgery, and residual PV obstruction were the predictors for reintervention (p < 0.05 for all). CONCLUSIONS The primary sutureless repair for the patients with mixed type TAPVD appeared to be safe and effective, resulting in no mortality and reintervention. There were nonsignificant trends toward improving survival and reintervention in the sutureless group. The patients who had sutureless repair and partially unrepaired PV revealed reasonable early and medium-term physiologic tolerance without need for reinterventions.

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.

Beneficial effects of vasopressors on right ventricular function in experimental acute right ventricular failure in a rabbit model.

BACKGROUND An acute increase in right ventricular (RV) afterload leads to RV dilation, reduced systolic function, and low cardiac output. It has previously been shown, experimentally, that an additional increase of left ventricular afterload by aortic constriction can reverse some of these changes. We studied the clinically more relevant effects of intravenous vasopressors on this phenomenon in an animal model. METHODS Acute RV failure was induced by pulmonary artery constriction in adult New Zealand white rabbits. We then assessed the effect of aortic constriction on the functional performance of the failing RV using conductance catheters. We compared the impact of aortic constriction on RV contractility with the effects of 0.05, 0.1, 0.5, and 1 mcg/kg × min(-1) norepinephrine and epinephrine. RESULTS Aortic constriction lead to increased RV end-systolic pressure-volume relation (RVESPVR 3.2 (±0.6) versus 5.2 (±0.7) mm Hg/mL (p = 0.0002). Cardiac output (131 (±23.7) versus 134.8 (±32.5) mL/min), and heart rate remained unchanged. Administration of norepinephrine and epinephrine lead to similar effects on RV contractility with the maximum increase in RVESPVR observed with 0.5 mcg/kg × min(-1) norepinephrine (RVESPVR 4.8 (±0.4) mm Hg/mL, p = 0.007). However, in contrast to aortic constriction, cardiac output also markedly increased during vasopressor therapy, the most significant effect seen with 1 mcg/kg × min(-1) epinephrine (214.8 (±46.8) mL/min, p = 0.04). CONCLUSIONS Aortic constriction improves RV contractility but not cardiac output in acute right heart failure. A comparable effect on RV functional performance with increased cardiac output was achieved by administration of systemic vasopressors. These data may have implications for management of clinical right heart failure.

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.