Differential Effects of Beta-Hydroxybutyrate Enantiomers on Induced Pluripotent Stem Derived Cardiac Myocyte Electrophysiology.

Beta-hydroxybutyrate (ßOHB), along with acetoacetate and acetone, are liver-produced ketone bodies that are increased after fasting or prolonged exercise as an alternative fuel source to glucose. ßOHB, as the main circulating ketone body, is not only a G-protein coupled receptor ligand but also a histone deacetylases inhibitor, prompting the reexamination of its role in health and disease. In this study, we compared the effects of two commercial ßOHB formulations an enantiomer R ßOHB and a racemic mixture ±ßOHB on induced pluripotent stem cell cardiac myocytes (iPS-CMs) electrophysiology. Cardiac myocytes were cultured in R ßOHB or ±ßOHB for at least ten days after lactate selection. Flouvolt or Fluo-4 was used to assay iPS-CMs electrophysiology. We found that while both formulations increased the optical potential amplitude, R ßOHB prolonged the action potential duration but ±ßOHB shortened the action potential duration. Moreover, ±ßOHB increased the peak calcium transient but R ßOHB reduced the peak calcium transient. Co-culturing with glucose or fatty acids did not ameliorate the effects, suggesting that ßOHB was more than a fuel source. The effect of ßOHB on iPS-CMs electrophysiology is most likely stereoselective, and care must be taken to evaluate the role of exogenous ßOHB in health and disease.

Long-term Results Using Glutaraldehyde-treated Homograft Pericardium in Congenital Heart Surgery.

BACKGROUND: This study reports the long-term outcomes using glutaraldehyde-treated cryopreserved homograft pericardium (CPH) in neonates, infants, children, and young adults undergoing congenital cardiac surgery. METHODS: A retrospective review was performed of all patients at a single institution (Rady Children's Hospital, San Diego, CA) who had undergone surgical implantation with CPH between 2006 and 2016. The study identified 134 consecutive patients who underwent implantation of a total of 276 patches. The baseline demographic characteristics, primary cardiac diagnosis, surgical characteristics, operative reports, and postoperative catheterization and reoperation reports were analyzed. The use of CPH was categorized by specific anatomic insertion site. RESULTS: The median age at patch implantation was 1.47 years (range, 1 day to 31.6 years). The numbers and locations of patch use were 124 for pulmonary arterial repair, 57 for repair of the aorta, 49 for septal repair, and 43 at other sites. At a median follow-up of 5.29 years, 9 patients had died (6.7%), but none of those deaths were related to CPH. Twelve patients (8.96%) underwent reoperations, and 18 patients (13.4%) underwent catheter interventions at sites of CPH implantation. The 10-year freedom from patch-induced reoperation and catheter intervention rates were 88.5% and 86.9%, respectively. Overall patch failure-free survival was 85.8% and 79.0% at 5 and 10 years, respectively. CONCLUSIONS: The use of CPH patch in the surgical correction of congenital heart disease is effective and durable, as evidenced by the low reintervention rates. These results are comparable to the early and midterm outcomes of other similarly used surgical patches.

Optical Imaging of Isolated Murine Ventricular Myocytes.

The ability to isolate adult cardiac myocytes has permitted researchers to study a variety of cardiac pathologies at the single cell level. While advances in calcium sensitive dyes have permitted the robust optical recording of single cell calcium dynamics, recording of robust transmembrane optical voltage signals has remained difficult. Arguably, this is because of the low single to noise ratio, phototoxicity, and photobleaching of traditional potentiometric dyes. Therefore, single cell voltage measurements have long been confined to the patch clamp technique which while the gold standard, is technically demanding and low throughput. However, with the development of novel potentiometric dyes, large, fast optical responses to changes in voltage can be obtained with little to no phototoxicity and photobleaching. This protocol describes in detail how to isolate adult murine myocytes which can be used for cellular shortening, calcium, and optical voltage measurements. Specifically, the protocol describes how to use a ratiometric calcium dye, a single-excitation calcium dye, and a single excitation voltage dye. This approach can be used to assess the cardiotoxicity and arrhythmogenicity of various chemical agents. While phototoxicity is still an issue at the single cell level, methodology is discussed on how to reduce it.

The effects of the ketone body ß-hydroxybutyrate on isolated rat ventricular myocyte excitation-contraction coupling.

ß-hydroxybutyrate is the primary ketone body produced by the body during ketosis and is used to meet its metabolic demands. The healthy adult heart derives most of its energy from fatty acid oxidation. However, in certain diseases, the heart alters its substrate preference and increases its ketone body metabolism. Little is known about the effects of ßOHB on ventricular myocyte excitation-contraction coupling. Therefore, we examined the effects of ketone body metabolism on single cell excitation-contraction coupling during normoxic and hypoxic conditions. Myocytes were isolated from adult rats, cultured for 18 h in RPMI 1640, RPMI 1640 no glucose, and M199, HEPES with/without various amount of ßOHB added. To simulate hypoxia, myocytes were incubated at 1%O2, 5% CO2 for 1 h followed by incubation at atmospheric oxygen (21%O2,5% CO2) for 30 min before recordings. Recordings were obtained using an IonOptix system at 36±1ᵒ C. Myocytes were paced at 0.5, 1, 2, 3, and 4 Hz. We found that exposure to ßOHB had no effect on excitation-contraction coupling. However, culturing cells with ßOHB results in a significant increase in both contraction and calcium in RPMI 1640 media. Dose response experiments demonstrated 0.5 mM ßOHB is enough to increase myocyte contraction in the absence of glucose. However, ßOHB has no measurable effects on myocytes cultured in a nutrient rich media, M199, HEPES. Therefore, ßOHB improves single cell excitation-contraction coupling, is protective against hypoxia, and may be a beneficial adaptation for the heart during periods of nutrient scarcity and or metabolic dysregulation.

Impaired mitophagy facilitates mitochondrial damage in Danon disease.

RATIONALE: Lysosomal associated membrane protein type-2 (LAMP-2) is a highly conserved, ubiquitous protein that is critical for autophagic flux. Loss of function mutations in the LAMP-2 gene cause Danon disease, a rare X-linked disorder characterized by developmental delay, skeletal muscle weakness, and severe cardiomyopathy. We previously found that human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from Danon patients exhibited significant mitochondrial oxidative stress and apoptosis. Understanding how loss of LAMP-2 expression leads to cardiomyocyte dysfunction and heart failure has important implications for the treatment of Danon disease as well as a variety of other cardiac disorders associated with impaired autophagy. OBJECTIVE: Elucidate the pathophysiology of cardiac dysfunction in Danon disease. METHODS AND RESULTS: We created hiPSCs from two patients with Danon disease and differentiated those cells into hiPSC-CMs using well-established protocols. Danon hiPSC-CMs demonstrated an accumulation of damaged mitochondria, disrupted mitophagic flux, depressed mitochondrial respiratory capacity, and abnormal gene expression of key mitochondrial pathways. Restoring the expression of LAMP-2B, the most abundant LAMP-2 isoform in the heart, rescued mitophagic flux as well as mitochondrial health and bioenergetics. To confirm our findings in vivo, we evaluated Lamp-2 knockout (KO) mice. Impaired autophagic flux was noted in the Lamp-2 KO mice compared to WT reporter mice, as well as an increased number of abnormal mitochondria, evidence of incomplete mitophagy, and impaired mitochondrial respiration. Physiologically, Lamp-2 KO mice demonstrated early features of contractile dysfunction without overt heart failure, indicating that the metabolic abnormalities associated with Danon disease precede the development of end-stage disease and are not merely part of the secondary changes associated with heart failure. CONCLUSIONS: Incomplete mitophagic flux and mitochondrial dysfunction are noted in both in vitro and in vivo models of Danon disease, and proceed overt cardiac contractile dysfunction. This suggests that impaired mitochondrial clearance may be central to the pathogenesis of disease and a potential target for therapeutic intervention.

Altered myocyte contractility and calcium homeostasis in alpha-myosin heavy chain point mutations linked to familial dilated cardiomyopathy.

Mutations in the human cardiac motor protein beta-myosin heavy chain (ßMHC) have been long recognized as a cause of familial hypertrophic cardiomyopathy. Recently, mutations (P830L and A1004S) in the less abundant but faster isoform alpha-myosin heavy chain (αMHC) have been linked to dilated cardiomyopathy (DCM). In this study, we sought to determine the cellular contractile phenotype associated with these point mutations. Ventricular myocytes were isolated from 2 month male Sprague Dawley rats. Cells were cultured in M199 media and infected with recombinant adenovirus containing the P830L or the A1004S mutant human αMHC at a MOI of 500 for 18 h. Uninfected cells (UI), human ßMHC (MOI 500, 18 h), and human αMHC (MOI 500, 18 h) were used as controls. Cells were loaded with fura-2 (1 µM, 15 min) after 48 h. Sarcomere shortening and calcium transients were recorded in CO2 buffered M199 media (36°±1 C) with and without 10 nM isoproterenol (Iso). The A1004S mutation resulted in decreased peak sarcomere shortening while P830L demonstrated near normal shortening kinetics at baseline. In the presence of Iso, the A1004S sarcomere shortening was identical to the ßMHC shortening while the P830L was identical to the αMHC control. All experimental groups had identical calcium transients. Despite a shared association with DCM, the P830L and A1004S αMHC mutations alter myocyte contractility in completely different ways while at the same preserving peak intracellular calcium.

Intermediate Results of Hybrid Versus Primary Norwood Operation.

BACKGROUND: In 2007 we began a hybrid program for hypoplastic left heart syndrome (HLHS) variants to potentially improve outcome in high-risk patients. During implementation we offered both hybrid and Norwood approaches to all risk categories. The purpose of this study was to perform a comparative analysis of intermediate survival. METHODS: Newborns were evaluated jointly for high-risk characteristics, including birth weight less than 2.5 kg, prematurity (especially < 35 weeks), central nervous system abnormalities, multiorgan failure, intact or severely restrictive atrial septum, severe ventricular dysfunction, and severe atrioventricular valve regurgitation. We prefer Norwood for standard risk and hybrid for high risk, but all groups crossed over into all treatment pathways resulting in the following 5 treatment groups: standard risk Norwood; high-risk Norwood; standard risk hybrid ductal stent (HDS); high-risk hybrid DS; and high-risk hybrid prostaglandin E1 (HPGE). We reviewed all consecutive patients from 2007 to 2012, obtained follow-up, and analyzed the results. RESULTS: Sixty-eight newborns presented (median 2.96 kg, 8 days); 29 (43%) were high and 39 (57%) were standard risk. There were 14 stage I hospital deaths strongly associated with risk: 3 of 39 standard (7.7%) and 11 of 29 high (38%, p = 0.002). Stage I discharge mortality was highest for high-risk Norwood and high-risk HPGE groups (p < 0.001). Actuarial survival up to 5 years demonstrated superior survival for Norwood versus hybrid (78.1% vs 56.4%, p = 0.0182). With risk stratification there was suboptimal survival for all 3 high-risk groups (p = 0.003); HDS fared better than HPGE but had higher birth weight (p < 0.001). CONCLUSIONS: While a risk-stratified approach for HLHS variant patients with selective use of hybrid palliation resulted in acceptable stage I mortality, the longer term mortality for high-risk patients remains higher than for standard risk regardless of treatment modality. Intrinsic patient risk factors (rather than treatment modality) likely determine long-term outcome in experienced centers. Our current high-risk approach has evolved to HPGE application with Norwood conversion whenever deemed medically possible.

Anomalous aortic origin of the left coronary artery: in-hospital cardiac arrest and death despite bed rest.

A ten-year-old female was admitted with syncope and a myocardial infarction, was resuscitated, and was diagnosed with anomalous left coronary artery from right aortic sinus. After initial stabilization, she was on bed rest in the intensive care unit awaiting surgery and experienced sudden arrest and could not be resuscitated, resulting in death.

Myosin light chain 2-based selection of human iPSC-derived early ventricular cardiac myocytes.

Applications of human induced pluripotent stem cell derived-cardiac myocytes (hiPSC-CMs) would be strengthened by the ability to generate specific cardiac myocyte (CM) lineages. However, purification of lineage-specific hiPSC-CMs is limited by the lack of cell marking techniques. Here, we have developed an iPSC-CM marking system using recombinant adenoviral reporter constructs with atrial- or ventricular-specific myosin light chain-2 (MLC-2) promoters. MLC-2a and MLC-2v selected hiPSC-CMs were purified by fluorescence-activated cell sorting and their biochemical and electrophysiological phenotypes analyzed. We demonstrate that the phenotype of both populations remained stable in culture and they expressed the expected sarcomeric proteins, gap junction proteins and chamber-specific transcription factors. Compared to MLC-2a cells, MLC-2v selected CMs had larger action potential amplitudes and durations. In addition, by immunofluorescence, we showed that MLC-2 isoform expression can be used to enrich hiPSC-CM consistent with early atrial and ventricular myocyte lineages. However, only the ventricular myosin light chain-2 promoter was able to purify a highly homogeneous population of iPSC-CMs. Using this approach, it is now possible to develop ventricular-specific disease models using iPSC-CMs while atrial-specific iPSC-CM cultures may require additional chamber-specific markers.

Association of complications with blood transfusions in pediatric cardiac surgery patients.

BACKGROUND: Blood product transfusion during cardiopulmonary bypass has been demonstrated to be associated with increased morbidity and mortality in adult cardiac surgery populations. The aim of this study was to characterize the risk-adjusted occurrence of postoperative complications and mortality in relation to intraoperative blood product transfusion in our pediatric cardiac surgery population. METHODS: A retrospective review was performed on 1,631 consecutive cardiopulmonary bypass cases to determine the effects of intraoperative blood product transfusion on selected outcomes. After adjusting for patient and operative risk factors, multivariate analysis was performed to determine the association between blood product transfusion and postoperative complications. Cox proportional hazards model was used to examine the relationship of packed red blood cell transfusion to hospital length of stay. RESULTS: Red blood cell and fresh frozen plasma transfusion was associated with pulmonary complications (adjusted odds ratio, 1.55; 95% confidence interval, 1.05 to 2.28; p=0.03). Red blood cell transfusion also correlated with prolonged hospital stay (p<0.01). Cryoprecipate transfusion was associated with postoperative pulmonary complications (adjusted odds ratio, 1.79; 95% confidence interval, 1.13 to 2.55; p=0.01), but decreased incidence of 30-day mortality (adjusted odds ratio, 0.44; 95% confidence interval, 0.23 to 0.85; p=0.02). Platelet transfusion was associated with decreased 30-day mortality (adjusted odds ratio, 0.51; 95% confidence interval, 0.28 to 0.93; p=0.04), but not overall mortality. CONCLUSIONS: Blood product transfusion was associated with an increased incidence of postoperative pulmonary complications and prolonged hospital length of stay, but not overall mortality. These findings suggest that minimizing blood product transfusion would be beneficial in the pediatric cardiopulmonary bypass surgery patient population.

Berlin Heart EXCOR pediatric ventricular assist device for bridge to heart transplantation in US children.

BACKGROUND: Recent data suggest that the Berlin Heart EXCOR Pediatric ventricular assist device is superior to extracorporeal membrane oxygenation for bridge to heart transplantation. Published data are limited to 1 in 4 children who received the device as part of the US clinical trial. We analyzed outcomes for all US children who received the EXCOR to characterize device outcomes in an unselected cohort and to identify risk factors for mortality to facilitate patient selection. METHODS AND RESULTS: This multicenter, prospective cohort study involved all children implanted with the Berlin Heart EXCOR Pediatric ventricular assist device at 47 centers from May 2007 through December 2010. Multiphase nonproportional hazards modeling was used to identify risk factors for early (<2 months) and late mortality. Of 204 children supported with the EXCOR, the median duration of support was 40 days (range, 1-435 days). Survival at 12 months was 75%, including 64% who reached transplantation, 6% who recovered, and 5% who were alive on the device. Multivariable analysis identified lower weight, biventricular assist device support, and elevated bilirubin as risk factors for early mortality and bilirubin extremes and renal dysfunction as risk factors for late mortality. Neurological dysfunction occurred in 29% and was the leading cause of death. CONCLUSIONS: Use of the Berlin Heart EXCOR has risen dramatically over the past decade. The EXCOR has emerged as a new treatment standard in the United States for pediatric bridge to transplantation. Three-quarters of children survived to transplantation or recovery; an important fraction experienced neurological dysfunction. Smaller patient size, renal dysfunction, hepatic dysfunction, and biventricular assist device use were associated with mortality, whereas extracorporeal membrane oxygenation before implantation and congenital heart disease were not.

Prospective trial of a pediatric ventricular assist device.

BACKGROUND: Options for mechanical circulatory support as a bridge to heart transplantation in children with severe heart failure are limited. METHODS: We conducted a prospective, single-group trial of a ventricular assist device designed specifically for children as a bridge to heart transplantation. Patients 16 years of age or younger were divided into two cohorts according to body-surface area (cohort 1, <0.7 m(2); cohort 2, 0.7 to <1.5 m(2)), with 24 patients in each group. Survival in the two cohorts receiving mechanical support (with data censored at the time of transplantation or weaning from the device owing to recovery) was compared with survival in two propensity-score-matched historical control groups (one for each cohort) undergoing extracorporeal membrane oxygenation (ECMO). RESULTS: For participants in cohort 1, the median survival time had not been reached at 174 days, whereas in the matched ECMO group, the median survival was 13 days (P<0.001 by the log-rank test). For participants in cohort 2 and the matched ECMO group, the median survival was 144 days and 10 days, respectively (P<0.001 by the log-rank test). Serious adverse events in cohort 1 and cohort 2 included major bleeding (in 42% and 50% of patients, respectively), infection (in 63% and 50%), and stroke (in 29% and 29%). CONCLUSIONS: Our trial showed that survival rates were significantly higher with the ventricular assist device than with ECMO. Serious adverse events, including infection, stroke, and bleeding, occurred in a majority of study participants. (Funded by Berlin Heart and the Food and Drug Administration Office of Orphan Product Development; ClinicalTrials.gov number, NCT00583661.).

Extended single-patch repair of supravalvar aortic stenosis: a simple and effective technique.

BACKGROUND: The optimal surgical procedure for repair of supravalvar aortic stenosis (SVAS) remains uncertain. Proponents of multisinus repair techniques suggest improved outcomes compared with the single-patch technique. We evaluated the outcomes after an extended single-patch technique for relief of SVAS. METHODS: A cross-sectional retrospective analysis was performed of all SVAS patients who underwent repair from 1996 to 2009. Patient, procedural, and hospital course data were obtained through a review of the medical records. At follow-up, patients were evaluated for residual SVAS gradient, valvar aortic stenosis, aortic insufficiency, and need for reintervention. RESULTS: Twenty-two patients (mean age, 2.4 ± 2.4 years) underwent repair of SVAS (discrete form, 59%). Mean preoperative peak gradient was 77 ± 27 mm Hg (range, 20 to 139 mm Hg). There were no hospital deaths. Median postoperative length of stay was 5 days (range, 3 to 68 days). Mean follow-up was 4.1 ± 3.5 years (range, 0.7 to 13 years). Follow-up Doppler echocardiography revealed a peak left ventricular outflow tract gradient of 10 ± 12 mm Hg (range, 0 to 41 mm Hg). No patient had significant valvar aortic stenosis or insufficiency. Two patients (9%) required catheter-based reintervention that was unrelated to the SVAS repair. CONCLUSIONS: This study demonstrates that a simple, extended single-patch technique for repair of SVAS provides excellent medium-term results. A durable reduction in gradient with low complication and recurrence rates can be achieved without the need for more complicated multisinus patch repairs.

Risk factor analysis for second-stage palliation of single ventricle anatomy.

BACKGROUND: Single ventricle hearts can be surgically palliated by a series of operations culminating in the Fontan procedure, which establishes a total cavopulmonary connection. The second-stage procedure creates a physiologic connection between the superior vena cava and the pulmonary artery. METHODS: From 1998 to 2010, 557 patients with single ventricle heart disease underwent second-stage surgical palliation. This cohort was retrospectively analyzed to assess patient outcome by a number of anatomic, physiologic, and procedural factors. The analysis excluded patients undergoing hybrid first-stage procedures. RESULTS: The median age at operation was 165 days (range, 59 days to 49 years). The most common anatomic subtypes were hypoplastic left heart syndrome (52%), tricuspid atresia (12%), unbalanced atrioventricular septal defect (10%), double inlet left ventricle (9%), or other (17%). Left ventricular hypoplasia was present in 70%. A hemi-Fontan procedure was done in 89%, and 11% received a bidirectional Glenn. Concomitant atrioventricular valve repair was necessary in 9%. Early mortality was 4.7%, and 5.9% died after discharge but before Fontan. No early or late deaths occurred in patients with tricuspid atresia and double inlet left ventricle. Multivariate analysis demonstrated ventricular dysfunction, atrioventricular valve regurgitation, and unbalanced atrioventricular septal defect were significant adverse risk factors for survival to Fontan. CONCLUSIONS: Second-stage palliation can be performed at low risk for patients with left ventricular dominance, but significant risk remains for patients with left ventricular hypoplasia and unbalanced atrioventricular septal defect. Atrioventricular valve insufficiency is a persistent problem that has not been neutralized by repair strategies.

Right pulmonary artery to left atrial fistula: a rare presentation.

Right pulmonary artery to left atrial fistula is a rare congenital vascular anomaly which usually presents with cyanosis, clubbing, dyspnea, and signs and symptoms of a right to left shunt. Paradoxical embolism to the brain resulting in cerebral abscess formation and death is a rare and ominous complication that has been described. We describe an unusual presentation with abdominal pain resulting from splenic infarction.

Tricuspid valve repair in hypoplastic left heart syndrome.

Tricuspid valve regurgitation (TR) remains an obstacle for staged palliation of hypoplastic left heart syndrome (HLHS). Because previous results from our institution suggested that posterior leaflet obliteration (PLO) is effective in tricuspid valve repair (TVR), we preferentially used this method. This report analyzes the effect of this preference on repair success and patient survival. All HLHS patients with 3-4+ preoperative TR undergoing TVR between 2002 and 2007 were retrospectively analyzed. Clinical and echocardiographic data were used to determine outcomes. Seventy-one percent (17 of 24) of patients had success at early outcome; the remaining 29% experienced early failure. Sixty-three percent (15 of 24) of patients demonstrated success at late outcome. Early outcome status was found to be a predictor of late outcome status (OR 22.9, P = 0.0037). Overall survival was 71% (17 of 24). Survival could not be shown to be associated with early or late outcome status (odds ratio = 0.96). A preference for PLO was found to give improved, long-lasting results for HLHS patients. Success at immediate outcome was predictive of success with time. PLO has the advantage of being simple and reproducible and produces good outcomes in this challenging group. Continued follow-up will be necessary to confirm long-term outcomes.

Bridging children of all sizes to cardiac transplantation: the initial multicenter North American experience with the Berlin Heart EXCOR ventricular assist device.

BACKGROUND: Beginning in 2000 and accelerating in 2004, the Berlin Heart EXCOR (Berlin Heart Inc Woodlands, TX) became the first pediatric-specific ventricular assist device (VAD) applied throughout North America for children of all sizes. This retrospective study analyzed the initial Berlin Heart EXCOR pediatric experience as a bridge to transplantation. METHODS: Between June 2000 and May 2007, 97 EXCOR VADs were implanted in North America at 29 different institutions. The analysis is limited to 73 patients (75%) from 17 institutions, for which retrospective data were available. RESULTS: Median age and weight at VAD implant were 2.1 years (range, 12 days-17.8 years) and 11 kg (range, 3-87.6 kg), respectively. The primary diagnoses were dilated cardiomyopathy in 42 (58%), congenital heart disease in 19 (26%), myocarditis in 7 (10%), and other cardiomyopathies in 5 (7%). Pre-implant clinical condition was critical cardiogenic shock in 38 (52%), progressive decline in 33 (45%), or other in 2 (3%). Extracorporeal membrane oxygenation was used as a bridge to EXCOR in 22 patients (30%). Device selection was left VAD (LVAD) in 42 (57%) and biventricular assist devices (BiVAD) in 31 (43%). The EXCOR bridged 51 patients (70%) to transplant and 5 (7%) to recovery. Mortality on the EXCOR was 23% (n = 17) overall, including 35% (11 of 31) in BiVAD vs 14% (6 of 42) in LVAD patients (p = 0.003). Multivariate analysis showed younger age and BiVAD support were significant risk factors for death while on the EXCOR. CONCLUSIONS: This limited but large preliminary North American experience with the Berlin Heart EXCOR VAD as a bridge to cardiac transplantation for children of all ages and sizes points to the feasibility of this approach. The prospective investigational device evaluation trial presently underway will further characterize the safety and efficacy of the EXCOR as a bridge to pediatric cardiac transplantation.

Outcomes of 1½- or 2-ventricle conversion for patients initially treated with single-ventricle palliation.

OBJECTIVE: As outcomes for the Fontan procedure have improved, it has become more difficult to select between a single-ventricle repair or biventricular repair for patients with complex anatomy and 2 ventricles. However, late complications after the Fontan procedure remain a concern. Our strategy, which has favored an aggressive preferential approach for biventricular repair in these patients, has also been applied to patients initially treated on a single-ventricle track elsewhere. METHODS: Nine patients (4 male patients) who had previously undergone the Fontan procedure (n=3) or bidirectional cavopulmonary shunting (n=6) with intent for a later Fontan procedure were referred to our center for complex 1½- or 2-ventricle repair over the last 10 years. Indications for conversion in these patients were protein-losing enteropathy (n=2), pulmonary arteriovenous malformation (n=1), and preference for biventricular anatomy (n=6). The conversion mainly consisted of takedown of the Fontan procedure or bidirectional cavopulmonary shunt connection, reconstruction of 1 or both of venae cavae, creation of an intraventricular pathway for left ventricular output, and placement of a right ventricle-pulmonary artery conduit (Rastelli-type operation). RESULTS: Five patients underwent 1½-ventricle repair, and 4 had complete biventricular repair. Median cardiopulmonary bypass and aortic crossclamp times were 202 minutes (range, 169-352 minutes) and 129 minutes (range, 100-168 minutes), respectively. There were 2 early deaths and 1 late death. At a median follow-up of 27 months (range, 3.3-99.8 months), all survivors are in New York Heart Association class I. CONCLUSIONS: Patients initially treated with intent to perform single-ventricle palliation can be converted to 1½- or 2-ventricle physiology with acceptable outcomes.

Intermediate-term clinical outcomes of primary biventricular repair for left ventricular outflow tract obstruction and ventricular septal defect.

OBJECTIVE: Primary biventricular repair for left ventricular outflow tract obstruction and ventricular septal defect remains challenging. The intermediate-term outcomes and risk factors for mortality remain undefined. METHODS: All patients undergoing primary biventricular repair of left ventricular outflow tract obstruction and ventricular septal defect from 1995 to 2008 at the C. S. Mott Children's Hospital, University of Michigan Health Systems were analyzed. RESULTS: Thirty-one patients (mean age, 18 days; 20 male) with a median follow-up of 6.7 years (range, 0.3-13.5 years) were identified. The ventricular septal defect was enlarged in 15 patients, and a limited atrial septal defect was constructed in 16 patients. There were 6 hospital and 2 late deaths. Ten-year patient survival was 72.3%. Lower body weight (P = .040), complete atrial septal defect closure (P = .026), and longer cardiopulmonary bypass time (P = .026) were risk factors of hospital mortality. An atrial septal defect was patent in 16 patients at discharge, 2 of whom required later surgical closure. Relief of recurrent left ventricular outflow tract obstruction was performed in 1 patient. No patient required pacemaker implantation. Five-year freedom from right ventricle-to-pulmonary artery conduit replacement was 39.3%. Smaller-sized conduit (P = .020) and use of aortic allograft (P = .048) were risk factors for early failure. CONCLUSION: Primary biventricular repair for patients with left ventricular outflow tract obstruction and ventricular septal defect provides good early and intermediate-term outcomes. Maintaining a small atrial septal defect may improve hospital mortality. Selective ventricular septal defect enlargement and careful construction of the intraventricular pathway result in a low incidence of recurrent left ventricular outflow tract obstruction, as well as avoidance of heart block. Maximizing valve diameter and avoiding aortic allografts may lengthen conduit longevity.