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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..

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.

Introduction: In 2016 the US government declared opioid misuse a public emergency. While most opioid related deaths can be attributed to overdose, recent data suggest a link between opioid use and cardiovascular disease. Further, epidemiological data suggest it may be sex dependent, with females (♀) being at a somewhat higher risk than males (♂). This is paradoxical because until menopause, ♀ have a lower risk of heart disease when compared to ♂. Healthy adult hearts express the δ and κ ORs, but not the μOR. Therefore, the overall goals of this study using a reductionist model were to: 1). To determine if there are sex specific differences in cardiac myocyte excitation-contraction coupling between ♂ and ♀ myocytes exposed to δ or κ OR agonists during normoxia/hypoxia. 2). Examine if 17β-Estradiol enhances or augments the effects of δ or κ OR stimulation. Methods: Myocytes were isolated from adult ♂ and ♀ Sprague-Dawley rats and cultured overnight in M199 HEPES media, or M199 HEPES media containing either 1 μM DADLE (δ agonist), 20 μM U50-488 (κ agonist), 100 nm 17β-Estradiol, 1μM DADLE + 100 nm 17β-Estradiol, or 20 μM U50-488 + 100 nm 17β-Estradiol. To simulate an infarct, a subset of the myocytes was incubated at 1%O 2 , 5% CO 2 for 4 hours + 10 nM isoproterenol followed by 60 min normoxia (21%O 2 , 5% CO 2 ) before recordings. Excitation-Contraction was measured using an IonOptix rig (IonOptix LLC, Milton MA) at 36±1° at 1 Hz pacing. Results: During normoxia, ♂ myocytes compared to ♀ myocytes had an increased peak contraction and peak Ca 2+ transient. The addition of 100 nM 17β-Estradiol did not affect peak contraction in either sex but decreased the Ca 2+ transient in ♂ myocytes while increasing it in ♀ myocytes. DADLE and U50-488 had no effect on ♀ myocyte contractility but decreased ♂ myocyte contractility by a minimum of 13% and a maximum of 26% with/without 100 nM 17β-Estradiol. ♀ myocytes were immune to the effects of hypoxia, even exhibiting a slight increase in their peak calcium compared to control conditions, arguably because of the addition of isoproterenol. ♂ myocytes on the other hand, had an overall decrease in excitation-contraction coupling during hypoxia which was made worse by OR stimulation. Conclusion: ♀ myocytes are immune to the detrimental effects of δ and κ OR stimulation.

β-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 βOHB 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 βOHB 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 βOHB had no effect on excitation-contraction coupling. However, culturing cells with βOHB results in a significant increase in both contraction and calcium in RPMI 1640 media. Dose response experiments demonstrated 0.5 mM βOHB is enough to increase myocyte contraction in the absence of glucose. However, βOHB has no measurable effects on myocytes cultured in a nutrient rich media, M199, HEPES. Therefore, βOHB 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.

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.Newborns were evaluated jointly for high-risk characteristics, including birth weight less than 2.5 kg, prematurity (especially35 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.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 (p0.001). 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 (p0.001).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.

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.

Mutations in the human cardiac motor protein beta-myosin heavy chain (βMHC) 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 βMHC (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 βMHC 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.

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.

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 2.1years (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.

Background Pulmonary allografts are commonly used in the reconstruction of the right ventricular outflow tract. However, in pediatric patients, allografts that are small enough are often unavailable. To downsize larger, more readily available conduits, one leaflet can be excised, forming a bicuspid valve. The aim of this study was to assess the intermediate-term durability of bicuspidized allografts compared with standard allografts. Methods Forty-seven patients who received a bicuspidized allograft from 1998 to 2008 were compared with 51 patients who received a standard allograft during the same time period. Outcome measures included need for and timing of reintervention, degree of pulmonary stenosis, insufficiency at most recent follow-up, and survival. Results On average, the bicuspidized allograft patients were younger, weighed less, and received smaller valves more frequently placed in a heterotopic position than the standard allograft patients. The mean peak gradient across the conduit and the degree of pulmonary insufficiency at discharge were similar between the comparison groups. No statistical differences in need for or timing of reintervention were observed between the surgical groups. Conclusions Bicuspidized allografts performed similarly to that of standard allografts with regard to the need for reintervention, the development of stenosis or regurgitation, and patient survival. Based on this patient sample, the bicuspidized allograft technique appears to provide an excellent option to expand the availability of small-sized allografts for the reconstruction of the right ventricular outflow tract.

ObjectivesHeart transplantation in patients with adult congenital heart disease is increasing, yet no large studies have defined how this subgroup differs from other adult recipients. We investigated outcomes and risk factors for mortality and retransplantation among patients with adult congenital heart disease compared with adult recipients.MethodsA review was performed of 18- to 45-year-old patients undergoing heart transplantation from 1990–2008 reported to the United Network for Organ Sharing database. Trends were compared between 2 eras: era 1 (1990–1998) and era 2 (1999–2008). Multivariable semiparametric hazard models identified factors associated with time-related death and retransplantation.ResultsOf 8496 patients identified, 575 had adult congenital heart disease. The prevalence of heart transplantation among adult recipients decreased by 28% over time (P

Objective The objective of this study was to review the long-term results of symptomatic patients with Ebstein anomaly in the neonatal period. Methods The medical records of 40 neonates with a diagnosis of Ebstein anomaly who were admitted to our institution between January 1988 and June 2008 were retrospectively reviewed. Primary outcomes studied included patient survival and need for reintervention. Results No early intervention was required in 16 of the 40 patients with a hospital survival of 94% (15/16) and no late mortality. The remaining 24 patients underwent surgical intervention in the neonatal period. A shunt alone was performed in 9 patients with an actuarial survival of 88.9% at 1 year and 76.2% at 5 and 10 years. For the patients undergoing intervention on the tricuspid valve, survival estimates for the 11 patients with a right ventricular exclusion procedure were 63.6% at 1, 5, and 10 years and 47.7% at 15 years compared with 25.0% at 1, 5, and 10 years for the 4 patients with tricuspid valve repair. All long-term survivors were in New York Heart Association class I or II, and only 1 patient required antiarrhythmic medication. Conclusion Symptomatic neonates with Ebstein anomaly requiring no intervention or shunting alone have good long-term survival. For patients needing intervention on the tricuspid valve, overall survival is lower. For these patients, right ventricular exclusion may be superior to tricuspid valve repair.

Cardiac muscle performance can be determined by factors intrinsic to each cardiac muscle cell, such as protein isoform expression. One protein whose expression plays a major role in determining cardiac performance is myosin. Myosin is the heart's molecular motor which transduces the chemical energy from ATP hydrolysis into the mechanical energy of each heartbeat. Alterations of myosin isoform expression are routinely associated with acquired and inherited cases of cardiomyopathy. For example, human heart failure is consistently associated with increased expression of a slow myosin motor isoform and a concomitant decreased expression of the heart's fast myosin motor isoform. Further, mutations of the cardiac myosin gene are the most common cause of inherited hypertrophic cardiomyopathy. Transgenic animal studies have provided insight into cardiac functional effects caused by myosin isoform gene switching (fast-to-slow myosin or slow-to-fast myosin) or by expression of a disease-related mutant motor. More direct structure-function analysis using acute gene transfer of myosin motors provides evidence that the inotropic state of cardiac muscle can be affected by motor protein isoform shifting independent of intracellular calcium handling. Because most therapies for the diseased heart target intracellular calcium handling, acute gene transfer of cardiac molecular motors to modulate heart performance offers a novel therapeutic strategy for the compromised heart. Although the development of safe vectors for therapeutic myosin gene delivery are in their infancy, studies focused on acute genetic engineering of the heart's molecular motor will provide a foundation for therapeutic vector development and insight into mechanisms that contribute to cardiomyopathy.

The initial Norwood procedure remains the highest risk operation for the staged repair of univentricular congenital malformations with associated systemic outflow obstruction. The modified Blalock-Taussig shunt (MBTS) has been implicated as a major cause of not only the operative mortality, but also associated morbidity and interstage attrition. The etiology of these events has often been attributed to the diastolic runoff and "coronary steal" associated with the MBTS, in addition to the delicate balance between systemic and pulmonary blood flow that characterizes all systemic-to-pulmonary artery shunts. Recently, there has been renewed interest in the right ventricle-to-pulmonary artery conduit as a source of pulmonary blood flow for the Norwood procedure as a potential method for minimizing the negative aspects of the MBTS. The current literature is contradictory, retrospective, and predominantly historically controlled. The Trial of Right Ventricular vs Modified Blalock-Taussig Shunt in Infants with Single Ventricle Defect Undergoing Staged Reconstruction, a randomized controlled clinical trial comparing the two techniques, is ongoing and may provide answers to this controversy.

Tricuspid valve regurgitation in patients with hypoplastic left heart syndrome is a cause of significant morbidity and mortality. Due to the multifactorial nature of its etiology, repair of the tricuspid valve may not always address the underlying problem and fail to improve late outcome. The role of tricuspid valve repair in this condition was examined in a series of patients with severe regurgitation following a Norwood procedure. The influence of surgical technique and right ventricular function were assessed in relation to late survival and tricuspid valve function. Tricuspid valve repair was successfully performed in the majority of patients and contributed to improved late outcomes. However, patients with an initially successful repair but significant right ventricular dysfunction tended to do poorly and the function of the valve often continued to deteriorate. Those with preserved ventricular function, even with continued tricuspid regurgitation, fared much better and achieved good results with additional attempts at repair.

The outlook for patients with hypoplastic left heart syndrome has dramatically improved over the past two decades. Universally fatal only 25 years ago, since that time outcomes for staged palliation have shown consistent improvement. Recent reports show that eight to nine patients from every ten can now leave the hospital after the Norwood procedure.1Attrition following the Norwood procedure, nonetheless, remains significant, with from five to fifteen percent of patients dying between the first and second stages of the Norwood sequence.1–4Only three-quarters of the patients undergoing surgery for hypoplastic left heart syndrome survive after five years, even at the centres reporting the best outcomes for the Norwood procedure.1,5In addition to the deaths, some patients are unable to progress through the three stages of reconstruction, and may require cardiac transplantation, or have no options for further therapy. There are many causes for these mortalities and morbidities following the Norwood procedure, including elevated pulmonary vascular resistance, cardiac arrhythmias, coronary arterial insufficiency, right ventricular failure, right ventricular volume overload due to shunt-dependent physiology, and tricuspid valvar regurgitation. Many of these factors are interrelated, and may form feedback loops, which serve to propagate their adverse effects on patients with hypoplastic left heart syndrome.

The congenital cardiac malformation characterized by discordant connections between the atriums and ventricles, as well as those between the ventricles and the arterial trunks, has been given many names. The terms atrioventricular discordance, l-transposition of the great arteries, ventricular inversion, and congenitally corrected transposition have all been used. Regardless of terminology, this complex congenital anomaly has only recently been studied to analyze the long-term effects of its natural history and outcomes following traditional surgical repair of the associated malformations which serve to uncorrect the circulatory pathways. As more patients survive into adulthood, the effects of this condition are now better understood, and the surgical approaches used in the past are being re-examined in light of longer-term follow up.

Objective Left ventricular outflow tract obstruction remains an early and late complication after repair of interrupted aortic arch and ventricular septal defect. We reviewed our experience with the selective management of the infundibular septum during primary repair to address left ventricular outflow tract obstruction. Methods From 1991 through 2001, all 27 patients presenting with interrupted aortic arch/ventricular septal defect and posterior deviation of the infundibular septum were analyzed. Fifteen patients with the smallest subaortic areas underwent myectomy or myotomy of the infundibular septum concomitant with interrupted aortic arch/ventricular septal defect repair. Results Patients undergoing myectomy-myotomy (Group I) had significantly smaller subaortic diameter indexes (0.83 ± 0.16 cm/m 2 ) when compared with those who had only interrupted aortic arch/ventricular septal defect repair (group 2: 0.99 ± 0.13 cm/m 2 , P = .012). Two hospital deaths occurred in group 1, and 1 occurred in group 2. No late deaths occurred. No patient in group 2 required reoperation. Six group 1 patients required 9 reoperations for left ventricular outflow tract obstruction. Five patients underwent resection of a new subaortic membrane. Only 1 patient had recurrent muscular left ventricular outflow tract obstruction. Three patients required a second reoperation, primarily related to aortic valve stenosis. Conclusions Interrupted aortic arch/ventricular septal defect with posterior malalignment of the infundibular septum can be repaired with low mortality in the neonatal period. Tailored to the degree of subaortic narrowing, resection or incision of the infundibular septum at the time of primary repair was very effective in preventing or prolonging the interval to recurrent left ventricular outflow tract obstruction compared with the published data. However, reoperation for left ventricular outflow tract obstruction, often related to the development of a new and discrete subaortic membrane or valvar stenosis, is still required in a subset of patients.

Objective Tremendous strides have been made in the outcomes for hypoplastic left heart syndrome and other functional single-ventricle malformations over the past 25 years. This progress relates primarily to improvements in survival for patients undergoing the Norwood procedure. Previous reports on risk factors have been on smaller groups of patients or collected over relatively long periods of time, during which management has evolved. We analyzed our current results for the Norwood procedure with attention to risk factors for poor outcome. Methods A single-institution review of all patients undergoing a Norwood procedure for a single-ventricle malformation from May 1, 2001, through April 30, 2003, was performed. Patient demographics, anatomy, clinical condition, associated anomalies, operative details, and outcomes were recorded. Results Of the 111 patients, there were 23 (21%) hospital deaths. Univariate analysis revealed noncardiac abnormalities (genetic or significant extracardiac diagnosis, P = .0018), gestational age ( P = .03), diagnosis of unbalanced atrioventricular septal defect ( P = .017), and weight of less than 2.5 kg ( P = .0072) to be related to hospital death. On multivariate analysis, only weight of less than 2.5 kg and noncardiac abnormalities were found to be independent risk factors. Patients with either of these characteristics had a hospital survival of 52% (12/23), whereas those at standard risk had a survival of 86% (76/88). Conclusions Although improvements in management might have lessened the effect of some of the traditionally reported risk factors related to variations in the cardiovascular anatomy, noncardiac abnormalities and low birth weight remain as a future challenge for the physician caring for the patient with single-ventricle physiology.

Background The ideal pulmonary valve replacement for children and adolescents remains elusive. Although favored by many surgeons, the cryopreserved pulmonary allograft tends to become rapidly incompetent and elicits an immune response. The SynerGraft process (Cryolife Inc, Kennesaw, GA) decellularizes a pulmonary allograft, leaving a scaffold of connective tissue. These grafts have been shown to decrease immune reactivity and become populated with host cells. Although theoretically these traits may improve durability, few data comparing SynerGraft-processed allografts (SynAs) (Cryolife Inc) with standard cryopreserved allografts are available. Methods A single institution review was performed for all SynAs implanted from their introduction in 2001 to January 2003. Twenty-six patients with SynAs and 26 age and diagnosis-matched controls receiving cryopreserved allografts were evaluated. Subjects were analyzed for demographics, survival, reintervention, and echocardiographic findings. Results There were no significant differences between groups in age, weight, valve diameter, orthotopic and heterotopic allograft position, or follow-up. On echocardiogram there was no difference in initial degree of allograft insufficiency or gradient. However, at mean follow-up of 19 ± 13 months, SynAs were significantly less regurgitant than cryopreserved allografts ( p = 0.017). Although all gradients were low, a significant difference between SynAs (7.6 ± 14 mm Hg) and cryopreserved allografts (14.6 ± 15.6 mm Hg; p = 0.012) had emerged. Survival was identical at 85% (22 of 26). Rates of reintervention were similar at 7% (2 of 26) for cryopreserved allografts and 3.8% (1 of 26) for SynAs ( p = 0.98). Conclusions At intermediate follow-up, the SynA demonstrated greater durability with less insufficiency and lower gradients. These characteristics are important to many patients with complex congenital heart disease; however, long-term effects on survival and reintervention remain unknown.

The Norwood procedure remains one of the highest-risk operations in congenital heart surgery. A significant contributor to this risk is thought to be the diastolic run-off into the modified Blalock-Taussig shunt (MBTS). In an effort to eliminate this risk, several groups have begun to utilize a right ventricle to pulmonary artery conduit (RVPAC), which decreases this diastolic "steal" of coronary blood flow. Whereas initial results with the RVPAC are encouraging, the postulated hemodynamic advantages are unproven. This case illustrates the positive hemodynamic changes by echocardiography after the replacement of a MBTS with a RVPAC in a patient after a Norwood procedure.

Technology for minimally invasive approaches to congenital heart disease is a rapidly evolving field. This case report reviews a novel approach to combining two of the newer technologies available to treat a pediatric patient with an atrial septal defect (ASD) and a vascular ring. This report is the first to describe the use of the da Vinci surgical system to assist in a thoracoscopic procedure for a pediatric patient. The da Vinci assisted division of the vascular ring, joined with an Amplatzer closure of the ASD, demonstrates how maximum benefit can be obtained for patients by combining emerging technologies.

Surgical palliation for hypoplastic left heart syndrome has become standard therapy in many centers throughout the world. Significant improvements in management, from preoperative diagnosis and intraoperative technique to postoperative care, have resulted in a dramatic increase in survival. With this improved survival, however, come new challenges and unforeseen problems. The first stage of the reconstructive surgery remains the highest risk procedure for the reason that establishing a stable circulation that is dependent on a single, volume-overloaded right ventricle with the potential for jeopardized coronary blood flow remains a surgical challenge. In this review, current management strategies for the conventional reconstructive surgical approach are examined.

Objective: Given the limited availability of small-sized cryopreserved pulmonary homografts, we implanted a series of Shelhigh NoReact porcine pulmonic valve conduits (SPVC). The aim of this study was to evaluate the short-term performance following implantation. Methods: From February 2000 to September 2000, the SPVC was implanted 25 times in 24 patients in the right ventricular outflow tract (RVOT) to correct congenital anomalies. The anatomical malformations were TOF/PA in eight patients, TGA/VSD/PS in four, truncus arteriosus in four, IAA/VSD/AS or AA in four, l-TGA/VSD in two and other in two. Age at operation was 2.8 ^ 3.9 years (mean ^ SD), including 12 patients under 1 year. The median conduit size was 14 mm (range, 10‐ 18). Results: At a mean follow-up of 23 ^ 5 months, two late deaths (8%) have occurred. Although they were not primarily conduit related, both showed severe conduit stenosis. Twenty-one conduits (84%) showed mild to severe conduit stenosis, regurgitation or both. Two patients underwent balloon dilatation for distal conduit stenosis. Twelve conduits (48%) in 11 patients were removed at a median of 12 months (range, 2 ‐18 months) due to RVOT obstruction in 11 and free conduit insufficiency with pseudoaneurysm in one. The typical findings of the explanted conduits were prominent intimal peel formation at the distal anastomosis without calcification. The actuarial freedom from reintervention at 18 months was 48 ^ 10%. Conclusions: Our experience of the SPVC with the diameter of 14 mm or less has revealed a high incidence of distal conduit stenosis due to intimal peel formation resulting in early conduit failure. These findings have led us to abandon its use when other options are available. q 2003 Elsevier Science B.V. All rights reserved.

Objective: Late results after traditional methods of repair of congenitally corrected transposition of the great arteries are poor. The combined arterial switch and Senning (double switch) operation may improve outcomes by using the morphologically left ventricle and mitral valve in the systemic circulation. In this report we review patient selection and intermediate results after the double switch operation for congenitally corrected transposition of the great arteries. Methods: Since 1993, a total of 35 patients with congenitally corrected transposition of the great arteries with two ventricles of adequate size and no valvular pulmonary stenosis were potential candidates for a double switch operation. Eleven were not yet in need of further treatment, and 1 died during evaluation. The remaining 23 patients were entered into a protocol leading to anatomic repair. Their hospital records were reviewed, and follow-up data were obtained to evaluate early and intermediate outcomes. Results: The 23 patients were candidates for anatomic repair because of right ventricular dysfunction or tricuspid regurgitation (n = 15) or associated uncorrected defects (n = 8). Pulmonary artery banding was performed in a total of 15 patients, either for left ventricular retraining (n = 11) or for congestive heart failure (n = 4). In 2 patients, aged 12 and 14 years, retraining was unsuccessful because of left ventricular dysfunction. Four patients with banding are currently awaiting repair. Eight patients proceeded to undergo double switch operations without preliminary pulmonary artery banding. To date, 17 patients have undergone double switch operations, with no early or late mortality. One patient required cardiac transplantation for progressive left ventricular failure after a preliminary banding and double switch operation done at 7 years of age. Ventricular function and tricuspid regurgitation remained stable or improved in all other cases. No patient has surgically acquired arrhythmias or significant residual hemodynamic conditions. All patients are alive and clinically well at a mean follow-up of 36 months (range 1 month-8 years). Conclusions: Congenitally corrected transposition of the great arteries with a normal pulmonary valve and two adequate ventricles can be managed with combined arterial switch and Senning operation with excellent intermediate results. Reconditioning the left ventricle may not be suitable for older patients. Late follow-up will be necessary to determine whether this management strategy provides a survival advantage for these patients. J Thorac Cardiovasc Surg 2003;125:500-7

Congenitally corrected transposition of the great arteries (ccTGA) is a rare defect characterized by discordant atrioventricular and ventriculoarterial connections. Symptoms result from one or a combination of associated cardiovascular malformations, including ventricular septal defect, pulmonary stenosis or atresia, and tricuspid valve dysfunction. Survival of patients with ccTGA is often determined by the associated anomalies, but even in isolation ccTGA results in a diminished life expectancy. Regurgitation of the tricuspid valve and decreased morphologic right ventricular function tend to develop and worsen over time. Anatomic repair by double switch technique may improve survival of patients with ccTGA by establishing the morphologic left ventricle in the systemic circulation.

Obscurin is a giant myofibrillar protein important for sarcomere structure, signaling, and maintenance of sarcoplasmic reticulum (SR) organization. Surprisingly, obscurin knockout mice develop normally and only show signs of a mild skeletal muscle myopathy. However, little is known about cardiac functions of obscurin. We characterized cardiac roles of obscurin and found no changes to cardiac physiology. One explanation for the lack of a cardiac phenotype in obscurin knockout mice is that other obscurin protein family members possess a functionally redundant role. We hypothesized that obscurin-like 1 (Obsl-1) is responsible for this redundancy, in part due to its shared ability to bind the sarcomeric proteins titin and myomesin. We generated double knockout (dKO) mice by crossing the obscurin-KO mice with a cardiac specific Obsl1-KO line to investigate the roles for these proteins in cardiac development and function. Although a majority of the dKO-mice died after 12 months of age, microscopic and ultrastructural analysis failed to reveal overt changes to sarcomere organization. Dramatic changes were observed, however, in SR structure and function. Specifically we observed: 1.) loss of SR structural integrity and apparent loss of SR content, and 2.) alterations to Ca2+ transients and in the levels of Ca2+ handling proteins in KO animals. The majority of these changes were more severe in dKO-mice. Furthermore, we employed serial blockface TEM technology to precisely measure the volume of the SR and mitochondria and noticed significant differences between KO and control animals. Physiologically, these mice develop a late onset cardiomyopathy characterized by increased systolic left ventricular internal dimension and alterations in hemodynamic properties at ∼12 mo. of age. Our data suggests that obscurin and Obsl1 are not critical for sarcomerogenisis, however are important for jointly organizing SR organization, cellular Ca2+ handling, and long-term survival in mice.

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.

Ebstein's anomaly of the tricuspid valve is characterized by a wide spectrum of severity. The condition involves more than a malformation of the tricuspid valve alone; a substantial portion of the right ventricle may be involved as well. Those patients presenting with symptoms in the first month of life represent a challenging group with a high mortality and uncertainty as to the best treatment options. In this review, the practical decision making process and the outcomes for neonates at one center are discussed.

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.

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 ( 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.

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.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.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 (p0.01). 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.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.

We report a case of a hypoplastic left heart syndrome with a nearly intact atrial septum and an obstructed anomalous pulmonary to systemic venous connection. Surgical atrial septectomy followed by bilateral pulmonary artery banding provided an optimal condition for the Norwood operation.

Options for mechanical circulatory support as a bridge to heart transplantation in children with severe heart failure are limited.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 to1.5 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).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 (P0.001 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 (P0.001 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%).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.).

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.

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.

Background Although good intermediate-term results for the Ross procedure in adults and older children have been reported, only short-term outcomes of this procedure in neonates and infants have been published. The objective of this study was to review our intermediate-term results of the Ross procedure for neonates and infants. Methods The records of all 31 neonates and infants undergoing a Ross procedure between March 1993 and June 2008 were reviewed. Major study outcomes included patient survival, autograft function, and need for reoperation. Results The median age at the time of operation was 18 days, and median weight was 3.95 kg. Fifteen patients had aortic stenosis with or without insufficiency, 2 patients had isolated severe aortic insufficiency, and 14 patients had aortic stenosis with other left-side heart lesions, such as arch obstruction or mitral valve disease. Twenty-five patients required aortic annular enlargement (Ross-Konno procedure), and 14 required concomitant arch or mitral valve surgery. There were 5 early and 2 late deaths at a median follow-up of 6.0 years (range, 1.1 to 15.4 years). All early deaths were in patients requiring concomitant arch or mitral valve repair. Actuarial survival rate was 76.7% at 5, 10, and 15 years. There were 19 reinterventions, including 2 procedures on the autograft. Overall freedom from reoperation was 59.1% at 5 years and 50.6% at 10 years. Freedom from autograft reoperation was 95.2% at 5 and 10 years and 63.5% at 15 years. Conclusions The Ross procedure for neonates and infants has good intermediate-term results with low mortality and acceptable rates of reintervention. The patients requiring concomitant arch or mitral valve surgery have higher initial operative risks although conditional survival remains good.

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.

Mitral valve repair is the preferred approach for congenital mitral valve stenosis in children. However, repairs in this population remain challenging.From 2001 to 2009, mitral valve repair was attempted in 20 consecutive congenital mitral valve stenosis patients. The median age and body weight at operation were 1.4 +/- 1.9 years and 7.4 +/- 4.1 kg, respectively. Multiple level left-side heart obstruction was present in 14 patients (70%). Moderate or more mitral insufficiency was present in 5 patients.The main etiology of the stenosis was valvular in 5 patients, supravalvular mitral ring in 4, single or predominant papillary muscle in 9, and hammock mitral valve in 2. Freedom from hospital death or transplantation was 85% (17 of 20). Two patients required replacement before discharge. In the 15 successfully repaired patients, mean mitral valve inflow pressure gradient improved from 13.9 +/- 2.7 mm Hg to 5.5 +/- 1.6 mm Hg (p0.0001). There were no late deaths at a mean follow-up of 46 +/- 31 months (range, 6.3 to 98.5). One patient required a second repair, and no patient has required replacement. At the last follow-up, mean mitral valve inflow pressure gradient was 7.5 +/- 4.1 mm Hg, and moderate or more mitral insufficiency was detected in 2 patients.Mitral valve repair for congenital mitral valve stenosis can be performed in this challenging population of patients with good early survival and freedom from transplantation. Conditional follow-up for successfully repaired patients demonstrates preserved mitral valve function without need for replacement.

Current inotropic therapies used to increase cardiac contractility of the failing heart center on increasing the amount of calcium available for contraction, but their long-term use is associated with increased mortality due to fatal arrhythmias. Thus, there is a need to develop and explore novel inotropic therapies that can act via calcium-independent mechanisms. The purpose of this study was to determine whether fast α-myosin molecular motor gene transfer can confer calcium-independent positive inotropy in slow β-myosin-dominant rabbit and human failing ventricular myocytes. To this end, we generated a recombinant adenovirus (AdMYH6) to deliver the full-length human α-myosin gene to adult rabbit and human cardiac myocytes in vitro. Fast α-myosin motor expression was determined by Western blotting and immunocytochemical analysis and confocal imaging. In experiments using electrically stimulated myocytes from ischemic failing hearts, AdMYH6 increased the contractile amplitude of failing human [23.9±7.8 nm (n=10) vs. AdMYH6 amplitude 78.4±16.5 nm (n=6)] and rabbit myocytes. The intracellular calcium transient amplitude was not altered. Control experiments included the use of a green fluorescent protein or a β-myosin heavy chain adenovirus. Our data provide evidence for a novel form of calcium-independent positive inotropy in failing cardiac myocytes by fast α-myosin motor protein gene transfer.—Herron, T. J., Devaney, E., Mundada, L., Arden, E., Day, S., Guerrero-Serna, G., Turner, I., Westfall, M., Metzger, J. M. Ca2+-independent positive molecular inotropy for failing rabbit and human cardiac muscle by α-myosin motor gene transfer.

Anatomic repair of congenitally corrected transposition of the great arteries has become a useful surgical strategy with potential advantages over conventional surgical repair. We describe early and intermediate outcomes after anatomic repair and analyze potential risk factors influencing these outcomes.A retrospective review was performed on all patients undergoing anatomic repair between January 1993 and January 2009. The primary outcome was in-hospital mortality. Variables potentially associated with outcome were identified a priori. Bivariate analyses were performed to determine the association between these variables and all outcome measures.In 65 patients who underwent anatomic repair, 35 had Senning/arterial switch and 30 had Senning/Rastelli. Early and intermediate survival rates for Senning/arterial switch operations were 94% and 91%, respectively. Repairs were successful in patients with tricuspid regurgitation, left ventricular outflow obstruction, and left ventricular dysfunction. Predictors of outcome were not identified in this subset. Early and intermediate survival rates for Senning/Rastelli operations were 77% and 60%, respectively. Longer aortic cross-clamp (p = 0.03) and cardiopulmonary bypass times (p = 0.01) were associated with mortality. Ventricular septal defect enlargement was associated with surgical heart block (p0.01). Age, prior procedures, atrial-apical discordance, and tricuspid regurgitation were not associated with outcome.Senning/arterial switch operations can be performed with excellent intermediate-term outcomes in patients with lesions previously thought to confer higher risk. Candidates for Senning/Rastelli procedures may be at increased risk for postoperative morbidity and mortality. More data are necessary to determine factors influencing outcome after anatomic repair.

ObjectiveWe evaluated N-acetylcysteine, a potent antioxidant, as prevention for renal dysfunction in infants undergoing cardiac surgery for dextro-transposition of the great arteries.MethodsTwenty-one neonates undergoing the arterial switch operation were randomized to receive either placebo or intravenous N-acetylcysteine. Serial data were collected on fluid balance, serum creatinine, inotropic support, cardiac output, and length of stay.ResultsHospital and 30-day survival was 100%. No serious adverse events were attributable to the drug. Subjects treated with N-acetylcysteine had a higher urine output at 24 hours (175 mL vs 96 mL; P < .01) and a shorter median time to first negative fluid balance (27 hours vs 39.5 hours; P = .02). There were no differences between groups in diuretic therapy, inotropic support, fluid intake, or chest tube output. Serum creatinine increased at 24 hours after the operation by a mean of 0.27 mg/dL with placebo (P < .01) but was unchanged with N-acetylcysteine treatment. By postoperative day 3, serum creatinine increased by 92% in the placebo group but only 38% in the N-acetylcysteine group (P = .04). Length of intensive care unit stay was shorter by an average of 5 days (P = .04) with N-acetylcysteine treatment.ConclusionsIn this pilot study, perioperative treatment with N-acetylcysteine resulted in improved urine output, shorter time to negative fluid balance, and attenuation of the rise in creatinine. These effects of N-acetylcysteine may translate to improved outcomes for infants undergoing complex cardiac operations.

Background The combination of an atrioventricular septal defect with a common atrioventricular junction guarded by a common valve, and double-outlet right ventricle, is a rare lesion that presents a challenge for surgical repair. This report describes our surgical approach and results in 16 patients undergoing biventricular repair for such a combination of lesions. Methods A retrospective analysis was performed for all patients undergoing biventricular repair of atrioventricular septal defect with common atrioventricular valve and double-outlet right ventricle between 1991 and 2008. Patients with tetralogy of Fallot and common atrioventricular valve were excluded from analysis. Early and actuarial outcomes were evaluated using the χ 2 test for categorical variables and Wilcoxon rank sum for ordinal variables. Results The median age at operation was 16 months. Heterotaxy syndrome was present in 12 of the 16 patients (9 right isomerism and 3 left isomerism), and 6 had concurrent totally anomalous pulmonary venous connections. Primary repair was achieved in 6 patients, and 10 underwent one or more prior operations (most frequently a shunt, banding of the pulmonary trunk, or repair of the anomalous pulmonary venous connections). Enlargement of the ventricular septal defect by resection of the muscular outlet septum was required in 11 patients, in whom the ventricular septal defect emptied entirely or primarily to the inlet of the right ventricle. A conduit was placed from the right ventricle to the pulmonary arteries in 13. There was 1 death before discharge from hospital, 1 late death, and 2 episodes of heart block. Among survivors, follow-up was complete with a median follow-up of 66 months. No patient had late obstruction of the left ventricular outflow tract. The presence of heterotaxy with totally anomalous pulmonary venous connections was associated with combined mortality and significant morbidity ( p = 0.008). Conclusions Although technically challenging, the surgical repair can be accomplished with acceptable early results. Heterotaxy syndrome, with concurrent anomalous connections of the pulmonary veins, represented the strongest identified risk factor for death or significant complication.

Background There is no ideal option for pulmonary valve replacement in children. Cryopreserved pulmonary allografts frequently demonstrate early valve regurgitation and may elicit an immune response. To improve these shortcomings, the SynerGraft process (CryoLife, Kennesaw, GA) decellularizes an allograft, leaving only connective tissue, which then becomes repopulated with host cells. A previous study at our institution demonstrated superior short-term durability of the SynerGraft-processed CryoValve SG compared with standard allografts. Longer-term impact of the technology remains unknown. Methods A single institution review was performed of all CryoValve SGs implanted between 2001 and 2004. Forty-one CryoValve SG patients and 41 age and diagnosis-matched standard allograft controls were evaluated. Demographics, survival, reintervention, and echocardiographic findings were analyzed. Results There were no significant differences between groups in demographics, valve diameter, orthotopic-heterotopic allograft position, or follow-up. For the entire cohort, there was no difference in early or late insufficiency or stenosis at a mean follow-up of 46 ± 14 months. However, freedom from moderate to severe insufficiency (>3+) was significantly better for CryoValve SG patients ( p = 0.05). In addition, for patients greater than 2 years of age, CryoValve SGs were significantly less regurgitant ( p = 0.045) and stenotic ( p = 0.041). Long-term survival was identical at 85% (35 of 41). Conclusions When compared with standard allografts, CryoValve SGs demonstrate superior freedom from significant insufficiency at intermediate follow-up. In older children, CryoValve SGs display less insufficiency and stenosis. For infants, patient age, valve diameter, previous conduit, and rapid somatic growth would likely be the predominant factors leading to allograft failure.

Objectives. To review early surgical outcomes in a contemporary series of adults with congenital heart disease (CHD) undergoing cardiac operations at the University of Michigan, and to investigate possible preoperative and intraoperative risk factors for morbidity and mortality. Methods. A retrospective medical record review was performed for all patients 18 years of age who underwent open heart operations by a pediatric cardiothoracic surgeon at the University of Michigan Congenital Heart Center between January 1, 1998 and December 31, 2004. Records from a cohort of pediatric patients ages 1-17 years were matched to a subset of the adult patients by surgical procedure and date of operation. Results. In total, 243 cardiac surgical operations were performed in 234 adult patients with CHD. Overall mortality was 4.7% (11/234). The incidence of major postoperative complications was 10% (23/234) with a 19% (45/23) minor complication rate. The most common postoperative complication was atrial arrhythmias in 10.8% (25/234). The presence of preoperative lung or liver disease, prolonged cardiopulmonary bypass and aortic cross clamp times, and postoperative elevated inotropic score and serum lactates were significant predictors of mortality in adults. There was no difference between the adult and pediatric cohorts in terms of mortality and morbidity. Conclusions. The postoperative course in adults following surgery for CHD is generally uncomplicated and early survival should be expected. Certain risk factors for increased mortality in this patient population may include preoperative presence of chronic lung or liver dysfunction, prolonged cardiopulmonary bypass and aortic cross- clamp times, and postoperative elevated inotropic score and serum lactate levels.