Sarah Gelehrter

Performance of CryoValve SG Decellularized Pulmonary Allografts Compared With Standard Cryopreserved Allografts

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.

Effects of Morphologic Left Ventricular Pressure on Right Ventricular Geometry and Tricuspid Valve Regurgitation in Patients With Congenitally Corrected Transposition of the Great Arteries

Congenitally corrected transposition of the great arteries (CCTGA) is associated with tricuspid regurgitation (TR), which has been postulated to arise from the effect of ventricular septal position on the attachments of the tricuspid valve. This study was performed to determine the effect of left ventricular (LV) pressure on right ventricular (RV) and LV geometry and the degree of TR. Serial echocardiograms were reviewed from, 30 patients with CCTGA who underwent pulmonary artery banding to train the morphologic left ventricle (n = 14) or left ventricle-to-pulmonary artery conduit placement and ventricular septal defect closure in conjunction with physiologic repair (n = 16). The degree of TR, the LV/RV pressure ratio, RV and LV sphericity indexes, and tricuspid valve tethering distance and coaptation length were analyzed. After pulmonary artery banding, an increase in LV systolic pressure to > or =2/3 systemic resulted in a decrease in TR from severe to moderate (p = 0.02). The percentage of patients with severe TR decreased from 64% to 18% (p = 0.06). The RV sphericity index decreased (p = 0.05), and the LV sphericity index increased (p = 0.02). After left ventricle-to-pulmonary artery conduit placement, a decrease in LV pressure to < or =1/2 systemic resulted in an increase in TR from none to mild (p = 0.003). In conclusion, these data indicate that LV pressure in patients with CCTGA affects the degree of TR and that septal shift caused by changes in LV and RV pressure is an important mechanism.

Non-invasive pulsed cavitational ultrasound for fetal tissue ablation: feasibility study in a fetal sheep model

Currently available fetal intervention techniques rely on invasive procedures that carry inherent risks. A non‐invasive technique for fetal intervention could potentially reduce the risk of fetal and obstetric complications. Pulsed cavitational ultrasound therapy (histotripsy) is an ablation technique that mechanically fractionates tissue at the focal region using extracorporeal ultrasound. In this study, we investigated the feasibility of using histotripsy as a non‐invasive approach to fetal intervention in a sheep model.

Screening for cardiac dysfunction in anthracycline-exposed childhood cancer survivors.

Purpose: To examine the utility and reliability of obtaining early echocardiographic measurements of left ventricular (LV) remodeling as well as blood biomarkers of cardiac injury in asymptomatic childhood cancer survivors at risk for LV dysfunction and congestive heart failure due to past exposure to anthracycline chemotherapy. Experimental Design: Using a cross-sectional design, anthracycline-exposed childhood cancer survivors with preserved ejection fraction (EF; ≥50%) were evaluated using early echocardiographic indices and blood biomarkers of LV dysfunction. Survivors treated with ≥300 mg/m2 anthracyclines [high risk (HR): n = 100] were compared with those treated with <300 mg/m2 anthracyclines [low risk (LR): n = 50] and matched healthy controls (HC: n = 50). All echocardiograms were interpreted by an institutional cardiologist and a study cardiologist blinded to risk status. Results: Time from diagnosis was comparable for HR (12.0 years) and LR (13.2 years, P = 0.8) survivors. Echocardiograms: HR had lower LV thickness-dimension ratio (Z-score: HR: −0.62, LR: −0.03, HC: −0.02; P < 0.001), increased LV wall stress (HR: 66.7 g/cm2, LR: 56.6 g/cm2, HC: 54.2 g/cm2; P < 0.01), and higher myocardial performance index (HR: 0.51, LR: 0.46, HC: 0.46; P < 0.01). Interobserver correlation (clinical/blinded reading) for all echocardiographic indices was excellent (range: R = 0.76–0.97, P < 0.001). Blood biomarkers: With the exception of NT-proBNP (r = 0.28, P < 0.01), there was no correlation between blood biomarkers (B-type natriuretic peptide, Troponin-T, ST-2, Galectin-3) and LV dysfunction. Conclusion: Childhood cancer survivors with preserved EF 10+ years from anthracycline exposure had dose-dependent changes in echocardiographic markers of LV dysfunction. Clin Cancer Res; 20(24); 6314–23. ©2014 AACR.

Biventricular Repair of Atrioventricular Septal Defect With Common Atrioventricular Valve and Double-Outlet Right Ventricle

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 chi(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.

Outcomes of Infants Weighing Three Kilograms or Less Requiring Extracorporeal Membrane Oxygenation After Cardiac Surgery

BACKGROUND Extracorporeal membrane oxygenation (ECMO) is the most common form of cardiac support for postcardiotomy cardiac failure in children. While its benefits have been thoroughly explored in infants weighing more than 3 kg, similar analyses are lacking in lower weight neonates. This single-center study investigated outcomes and risks for poor survival among infants weighing 3 kg or less. METHODS A retrospective review of infants 3 kg or less who required postcardiotomy ECMO support was performed (January 1, 1999 to December 31, 2010). Primary outcome was 30-day survival after decannulation. Factors analyzed for association with poor outcome included demographics, cardiac anatomy, bypass and circulatory arrest times, total ECMO support time, postoperative lactate, inotrope use, and need for renal replacement therapy. RESULTS During the study period, 64 patients weighing 3 kg or less required postcardiotomy ECMO. Median gestational age and age at ECMO initiation were 38 weeks (interquartile range, 36 to 39) and 7 days (interquartile range, 4 to 9), respectively, with median ECMO support time of 164 hours (interquartile range, 95 to 231). Overall 30-day survival after decannulation was 33%. Factors associated with poor outcome were longer duration of support (231 hours or more, 12% survival, versus less than 231 hours, 40% survival; p = 0.05) and renal replacement therapy (n = 36, survival 17% versus 54%; p = 0.002). Multivariable regression analysis identified renal replacement therapy as the only independent factor associated with poor survival (odds ratio 4.3, 95% confidence interval: 1.3 to 14.9, p = 0.02). CONCLUSIONS For infants weighing 3 kg or less, 30-day survival after decannulation after cardiac ECMO is poor. Factors associated with poor prognosis were need for renal replacement therapy and longer duration of ECMO support. These findings may provide a useful guide for medical decision making among this unique, high-risk patient group.

Strategies to Prevent Anthracycline-Related Congestive Heart Failure in Survivors of Childhood Cancer

Cardiovascular complications are a leading cause of therapy-related morbidity and mortality in long-term survivors of childhood malignancy. In fact, childhood cancer survivors are at a 15-fold risk of developing CHF compared to age-matched controls. There is a strong dose-dependent association between anthracycline exposure and risk of CHF, and the incidence increases with longer followup. Outcome following diagnosis of CHF is generally poor, with overall survival less than 50% at 5 years. The growing number of childhood cancer survivors makes it imperative that strategies be developed to prevent symptomatic heart disease in this vulnerable population. We present here an overview of the current state of knowledge regarding primary, secondary, and tertiary prevention strategies for childhood cancer survivors at high risk for CHF, drawing on lessons learned from prevention studies in nononcology populations as well as from the more limited experience in cancer survivors.

Effects of N-acetylcysteine on renal dysfunction in neonates undergoing the arterial switch operation.

OBJECTIVE We evaluated N-acetylcysteine, a potent antioxidant, as prevention for renal dysfunction in infants undergoing cardiac surgery for dextro-transposition of the great arteries. METHODS Twenty-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. RESULTS Hospital 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. CONCLUSIONS In 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.

Non-invasive fetal therapy using histotripsy: Feasibility study in the sheep model

Pulsed cavitational ultrasound, or histotripsy, has been shown to be an effective technique to mechanically fractionate tissue through controlled cavitation. In this study, we investigate the feasibility of using histotripsy as a therapeutic tool to non-invasively fractionate and remove fetal tissue. Pregnant ewes at 102–129 days into gestation were exposed to histotripsy by a focused 1 MHz transducer coupled to the maternal abdominal wall. The fetal heart, kidney and liver were exposed to short ultrasound pulses (≪10 µs) at a 1 kHz pulse repetition rate and 10–16 MPa peak negative pressure. The entire procedure was guided and monitored by real-time ultrasound imaging. A total of 11 experiments were performed and preliminary results show that with suitable acoustic windows, histotripsy was able to generate a cavitation bubble cloud at the targeted fetal tissue and create mechanical tissue fractionation and removal. Morphological and histological assessment of the treated tissue confirmed that lesion locations corresponded to regions where the cavitation bubble cloud was observed. These results suggest that histotripsy has potential to become a non-invasive clinical tool for early fetal intervention on congenital anomalies such as prenatal treatment for hypoplastic left heart syndrome.

Accuracy of the Fetal Echocardiogram in Double‐outlet Right Ventricle

OBJECTIVE Double-outlet right ventricle (DORV) is a complex congenital heart defect with heterogeneous anatomy. Patients require a variety of surgical interventions, and the long-term prognosis is variable. Therefore, accurate prenatal diagnosis is important in providing parents with appropriate counseling. DESIGN Medical records were reviewed in patients with a diagnosis of DORV who had fetal echocardiography at our institution from 1998 to 2004. Pre- and postnatal diagnoses were compared, anticipated surgical procedure was compared with surgery performed, and neonatal outcome was assessed. RESULTS The study group consisted of 49 fetal patients with 6 in utero deaths (including 4 terminations), 2 patients lost to follow-up, and 41 live births. Postnatal echocardiograms or autopsy results were available on 42 patients. The overall accuracy of fetal echocardiography in making a correct diagnosis of DORV was 76%. Accurate prenatal prediction of the type of cardiac surgery that would be performed was made in 91% of patients who had surgery. Among live births, survival to hospital discharge was 76%. Survival was 50% in patients with extracardiac or chromosomal anomalies, compared with 92% in infants without additional anomalies. CONCLUSION In most cases, careful evaluation by fetal echocardiography can determine essential anatomic details in fetuses with DORV with enough accuracy to allow for accurate counseling regarding the type of surgery needed. Survival is better than previously reported but is poor in patients with extracardiac or chromosomal abnormalities.