Farhan Zafar

Pediatric heart transplant waiting list mortality in the era of ventricular assist devices

BACKGROUND Earlier reviews have reported unacceptably high incidence of pediatric heart transplant (PHT) waiting list mortality. An increase in ventricular assist devices (VAD) suggests a potential positive effect. This study evaluated PHT waiting list mortality in the era of pediatric VADs. METHODS United Network of Organ Sharing (UNOS) database from 1999 to 2012 showed 5,532 pediatric candidates (aged ≤ 18 years) actively listed for PHT: 2,191 were listed in 1999 to 2004 (Era 1) and 3,341 were listed in 2005 to 2012 (Era 2). RESULTS Waiting list mortality was lower in Era 2 (8%) vs Era 1 (16%; p < 0.001). VAD therapy was used more frequently in Era 2 (16%) than in Era 1 (6%; p < 0.001) and was associated with better waiting list survival (p < 0.001). There were more UNOS Status 1A patients in Era 2 (80%) vs Era 1 (68%; p < 0.001). Independent predictors of waiting list mortality included weight < 10 kg (odds ratio [OR], 2.7 95% confidence interval [CI], 1.1-6.9), congenital heart disease diagnosis (OR, 2.4; 95% CI, 1.9-3.0), blood type O (OR, 2.2; 95% CI, 1.8-2.8)], extracorporeal membrane oxygenation (OR, 1.5; 95% CI, 1.1-2.2), mechanical ventilation (OR, 1.8; 95% CI, 1.4-2.3), and renal dysfunction (OR 1.6; 95% CI, 1.2-2.0). Independent predictors of survival on the waiting list included VAD therapy (OR 4.2; 95% CI, 2.4-7.6), cardiomyopathy diagnosis (OR 3.3; 95% CI, 2.4-4.6), blood type A (OR, 2.2; 95% CI, 1.8-2.8), UNOS list Status 1B (OR, 1.9; 95% CI, 1.2-3.0), listed in Era 2 (OR 1.8; 95% CI, 1.4-2.2), and white race (OR 1.3; 95% CI, 1.1-1.6). CONCLUSIONS Despite an increase in the number of children listed as Status 1A, there was more than a 50% reduction in waiting list mortality in the new era. Irrespective of other factors, patients supported with a VAD were 4 times more likely to survive to transplant.

Current Expectations for Surgical Repair of Isolated Ventricular Septal Defects

BACKGROUND Ventricular septal defect (VSD) is the most commonly recognized congenital heart defect. With the development of device closure for intracardiac defects, we sought to evaluate current expectations for surgical closure of isolated VSD. METHODS Between January 1, 2000, and December 31, 2006, 215 patients underwent isolated VSD repair at a median age of 10 months (range, 20 days to 18 years) and a median weight of 7 kg (range, 2 to 66 kg). The following VSD types were found: 172 perimembranous (80%), 28 supracristal (13%), 6 inlet (3%), and 9 muscular (4%). One hundred eight patients (50%) had evidence of congestive heart failure or failure to thrive preoperatively. Thirty-one patients (14%) had aortic valve cusp prolapse, and 63 (29%) had genetic abnormalities. RESULTS Incidence of significant postoperative complications was extremely low. No patient underwent reoperation for a residual VSD. None had complete heart block. One operative mortality (0.5%) and 2 late deaths (0.9%) occurred. Median postoperative hospital length of stay was 5 days (range, 2 to 187 days). In the immediate postoperative period, 6 patients (2.8%) required reoperation. No patients were discharged on antiarrhythmic agents, had complete heart block, or required permanent pacing. At mean follow-up of 2.1 +/- 2.0 years, 99.5% (211 of 212) of patients were asymptomatic from a cardiac standpoint. None exhibited greater than mild new-onset tricuspid valve regurgitation. No aortic valve injuries occurred. CONCLUSIONS Surgical closure of isolated VSD is a safe, effective therapy. Risk of death, complete heart block, and reoperation is minimal. As new technologies for VSD closure evolve, results such as these should be considered when evaluating patients, choosing therapeutic options, and counseling families.

Impact of antibodies against human leukocyte antigens on long-term outcome in pediatric heart transplant patients: An analysis of the United Network for Organ Sharing database

OBJECTIVES Controversy exists regarding the importance of circulating antibodies as determined by panel-reactive antibody screening as a risk factor for graft failure in pediatric patients undergoing heart transplantation. This study sought to determine the association of elevated anti-human leukocyte antibodies with long-term survival in pediatric heart transplant patients. METHODS The United Network for Organ Sharing registry was queried for pediatric patients (aged < 18 years at listing) with panel-reactive antibody levels obtained before heart transplantation from 1987 through 2004. Survival analysis methods were used to assess the association of elevated panel-reactive antibodies with long-term graft and patient survival. RESULTS Panel-reactive antibodies were obtained before transplantation from 3534 patients, median age 4 years (interquartile range 0-12 years). Most, 2711 (77%), had no detectable panel-reactive antibodies, 436 (12%) had panel-reactive antibodies of 1% to 10%, and 387 (11%) had panel-reactive antibodies greater than 10%. Patients with panel-reactive antibodies greater than 10% were more likely to be older (P = .04), have congenital heart disease (P < .001), and have a longer wait list time (P = .006). Patients with panel-reactive antibodies greater than 10% had significantly worse graft survival and patient survival than did patients with undetectable panel-reactive antibodies and panel-reactive antibodies of 1% to 10% (P < .05 for all). Controlling for confounding variables, elevated panel-reactive antibodies as a continuous variable and panel-reactive antibodies greater than 10% as a categorical variable were independently associated with decreased graft survival (P = .04 and P = .02, respectively). CONCLUSIONS Elevated panel-reactive antibodies are independently associated with worse long-term graft survival in pediatric patients undergoing heart transplantation. Further study is needed to determine the optimal management of this high-risk population.

Outcomes of Heart Failure–Related Hospitalization in Adults with Congenital Heart Disease in the United States

BACKGROUND Heart failure (HF) accounts for >3 million hospital admissions annually in adults with acquired cardiovascular disease, but there are limited data on HF admissions in adults with congenital heart disease (ACHD). The purpose of this study was to test the hypotheses that HF admissions are common in ACHD and associated with significant morbidity and mortality. METHODS The 2007 Nationwide Inpatient Sample was used to assess national prevalence, morbidities, and risk factors for mortality during hospitalizations among ACHD with HF. RESULTS Of the 84,308 (95% CI 71,345-97,272) ACHD admissions in the United States in 2007, 17,193 (95% CI 14,157-20,229) had a diagnosis of HF (20%). ACHD with HF was associated with an increased risk of death compared to ACHD without HF (OR 3.3, 95% CI 2.6-4.1). On multivariable analysis independent risk factors for mortality included nonoperative intubation (OR 6.1, 95% CI 3.3-11.4), sepsis (OR 4.3, 95% CI 2.4-7.4), and acute myocardial infarction (OR 3.2, 95% CI 1.8-5.7). Cardiac defects associated with an increased risk of mortality included ventricular septal defects (VSDs) (OR 1.8, 95% CI 1.0-3.4). CONCLUSIONS In this large population-based study, HF-related hospitalizations were common in ACHD and associated with an increased risk of death compared to non-HF admissions. The risk of mortality is increased with the diagnoses of VSDs and the presence of specific comorbidities such as respiratory failure and sepsis.

Repeat Sternotomy in Congenital Heart Surgery: No Longer a Risk Factor

BACKGROUND The risk of repeat sternotomy (RS) is often taken into account when making clinical management decisions. Current literature on RS suggests a risk of approximately 5% to 10% for major morbidity. We sought to establish the true risk of RS in a contemporary pediatric series. METHODS All RS between October 2002 and August 2006 were analyzed (602 RS in 558 patients). Median age was 3.6 years (range, 0.1 to 45.1); weight, 14.2 kg (2.0 to 112.2). Operations performed at RS were Glenn 22% (131), Fontan 21% (129), aortic valve repair/replacement 12% (72), right ventricle-pulmonary artery conduit 11% (67), Rastelli 7% (39), heart transplant 5% (31), and other 22% (133). Forty-seven percent of patients (280) had single-ventricle physiology. Incidence of second sternotomy was 67% (406), third 28% (166), fourth 4% (24), fifth 0.8% (5), and sixth 0.2% (1). A major injury upon RS was defined as one causing hemodynamic instability requiring vasopressor support or emergent transfusion; femoral cannulation or emergent cardiopulmonary bypass; and any morbidity. A minor injury is any other injury during RS. RESULTS The incidence of a major injury was not different between RS (0.3%; 2 of 602) and first-time sternotomy (0%; 0 of 1,274; p > 0.1). Incidence of a minor injury was 0.66% (4 of 602). No injury resulted in hemodynamic instability, neurologic injury, or death. Two patients (0.3%) required a nonemergent blood transfusion secondary to injury. (Nonemergent was defined as adminstration rate of less than 0.2 cc/kg/min and less than 10 cc/kg in total.) Femoral cannulation was performed in 4 of 602 RS cases (< 0.6%). Sternal wound infection was 0.5% (3 of 602); reoperation for postoperative bleeding was 1% (8 of 602). Median intensive care unit stay was 3 days (1 to 174); median hospital stay was 7 days (1 to 202). Hospital survival was 98%. CONCLUSIONS Repeat sternotomy can represent a negligible risk of injury and of subsequent morbidity or mortality. Therefore, the choice of management strategies for patients should not be affected by the need for RS.

Fenestration during Fontan palliation: Now the exception instead of the rule

OBJECTIVE Fenestration during Fontan palliation has traditionally been used to decrease surgical morbidity and mortality, particularly in high-risk cases. Potential limitations include oxygen desaturation, risk of paradoxic embolism, and need for late intervention. Our practice has evolved away from routine fenestration with increased extracardiac conduit use. We reviewed our experience with Fontan palliation and retrospectively assessed outcomes with decreased fenestration. METHODS Between January 2002 and April 2008, 226 patients underwent primary Fontan palliation. Outcomes were assessed by hospital stay, chest drain duration, short- and long-term survivals, and late interventions. RESULTS Anatomic subtypes were single left ventricle (n = 88, 38.9%), single right ventricle (n = 78, 34.5%), common ventricle (n = 19, 8.4%), and heterotaxy syndrome (n = 41, 18.1%). Lateral tunnel connection was created in 69 patients (30.5%); extracardiac connection was created in 157 (69.5%). Mean age and weight at surgery were 4.3 +/- 3.8 years and 17.2 +/- 9 kg, respectively. In 2002, 14 of 16 patients (87.5%) had fenestrated Fontan circulations, versus 2 of 32 (6.3%) in 2008. Mean hospital stay was 10.8 +/- 8.8 days. Survival to discharge or 30 days was 98.7%. There were 2 (0.9%) late deaths during mean follow-up of 2.0 +/- 1.7 years. Outcomes were equivalent between fenestrated and nonfenestrated procedures across anatomic subtypes. CONCLUSIONS Highly selective use of Fontan fenestration is achievable while maintaining excellent outcomes without increased surgical morbidity or mortality, irrespective of anatomic subtype. Risks of hypoxia, systemic embolism, and late instrumentation can be avoided in most cases.

Outcomes of Hospitalization in Adults in the United States With Atrial Septal Defect, Ventricular Septal Defect, and Atrioventricular Septal Defect

Atrial septal defect, ventricular septal defect (VSD), and atrioventricular septal defect (AVSD) are among the most common congenital heart lesions, with most children surviving to adulthood. However, the clinical course of these patients is largely unknown, particularly pertaining to inpatient care. The purpose of this study was to assess hospitalizations for septal defects in adults with congenital heart disease (CHD) and risk factors associated with significant morbidity and mortality. The 2007 Nationwide Inpatient Sample was used to assess national prevalence of hospitalizations in adults with CHD with septal defects. Co-morbidities and risk factors for mortality were also determined. There were 84,308 adult CHD admissions in the United States in 2007. Fifty-four percent of adult CHD admissions had diagnoses of septal defects, with 48% having atrial septal defect, 7% having VSD, and 0.4% having AVSD. Overall in-hospital mortality was 2.1%. Common co-morbidities included arrhythmias (31%), heart failure (20%), and diabetes mellitus (18%). On multivariable analysis, independent risk factors for mortality included presence of VSD (odds ratio 3.1, 95% confidence interval [CI] 1.5 to 6.5), trisomy 21 (odds ratio 2.9, 95% CI 1.1 to 7.5), and pulmonary hypertension (odds ratio 1.5, 95% CI 1.0 to 2.4). In conclusion, this study of hospitalizations in adults with septal defects found that admissions are common and associated with significant co-morbidities. Overall mortality is low but is increased in patients with VSD. Cardiac and noncardiac co-morbidities are commonly encountered. Many noncardiac conditions, including trisomy 21 and the youngest and oldest groups, are associated with an increased risk of death.

The evolving role of the total artificial heart in the management of end-stage congenital heart disease and adolescents.

Advances in medical therapies have yielded improvement in morbidity and a decrease in mortality for patients with congenital heart disease, both surgically palliated and uncorrected. An unintended consequence is a cohort of adolescent and adult patients with heart failure who require alternative therapies. One intriguing option is placement of a total artificial heart (TAH) either as a bridge to transplant or as a destination therapy. Of the 1091 Jarvik-7 type TAH (Symbion, CardioWest and SynCardia) placed between 1985 and 2012, only 24 have been performed in patients with congenital heart disease, and a total of 51 were placed in patients younger than 21. At our institution, the SynCardia TAH was implanted in a 19-year-old patient with cardiac allograft failure because of chronic rejection and related multisystem organ failure including need for hemodialysis. Over the next year, she was nutritionally and physically rehabilitated, as were her end organs, allowing her to come off dialysis, achieve normal renal function and eventually be successfully transplanted. Given the continued growth of adolescent and adult congenital heart disease populations with end-stage heart failure, the TAH may offer therapeutic options where previously there were few. In addition, smaller devices such as the SynCardia 50/50 will open the door for applications in smaller children. The Freedom Driver offers the chance for patients to leave the hospital with a TAH, as does the AbioCor, which is a fully implantable TAH option. In this report, we review the history of the TAH and potential applications in adolescent patients and congenital heart disease.

Tetralogy of Fallot Repair: The Right Ventricle Infundibulum Sparing (RVIS) Strategy

Despite the excellent operative survival for tetralogy of Fallot (TOF) repair, well-documented long-term complications and reduced life expectancy remain challenges for these patients and their clinicians. In an attempt to change the natural history of repaired TOF, we at Texas Childrens Hospital (Houston, TX) have developed a management strategy not focused on age, but rather focused on preserving the right ventricular (RV) infundibulum. The RV infundibulum sparing (RVIS) repair of TOF consists of a transatrial and transpulmonary approach to close the ventricular septal defect and resect RV infundibular muscle coupled with a mini (< 5 mm) transannular patch or no ventricular incision. This strategy is applied with the ambition of decreasing the well-documented, long-term complications of TOF repair with large right ventriculotomies such as RV dilation, arrhythmias, need for pulmonary valve replacement, and RV failure. The RVIS strategy is an attempt based on our current knowledge and experience to optimize the time of repair so that we can not only maximize the early operative results but the long-term effects of this approach as these children mature into adolescents and adults. We have uniformly applied the RVIS strategy since 1995, which includes over 320 isolated TOF patients. We are currently reviewing this cohort in hopes that it will strengthen our beliefs and known results as well as give us more insight into whether the RVIS strategy can change the natural history of repaired TOF.

Is mechanically bridging patients with a failing cardiac graft to retransplantation an effective therapy? Analysis of the United Network of Organ Sharing database.

BACKGROUND The results of bridging patients with cardiac allograft failure to retransplantation (ReTx) with mechanical circulatory support (MCS) have not been well studied. The United Network of Organ Sharing (UNOS) database was used to analyze outcomes of patients successfully bridged with MCS to cardiac ReTx. METHODS Of 1,690 cardiac ReTx identified in the UNOS database from October 1987 to July 2011, 149 (8.8%) were bridged to ReTx with MCS. RESULTS Patients bridged to ReTx with MCS had a poorer survival than patients not bridged (p < 0.0001). ReTx after ventricular assist device (VAD) support had better survival than ReTx after extracorporeal membrane oxygenation (ECMO; half-life, 3.9 years vs 61 days, p = 0.026). For patients bridged to ReTx, graft survival was 40% for ReTx within 1 year of primary Tx vs 64% (p = 0.003). When ReTx was performed 1 year after cardiac Tx, survival was similar in patients bridged with a VAD and those not bridged (mean, 7.5 vs 8.7 years; p = 0.8). Survival for patients bridged to ReTx with ECMO was consistently worse (p ≤ 0.05) in all analyses. The 1-year survival of ReTx after VAD performed in 2003 to 2011 (67%) was better than in the earlier era of 1987 to 2002 (37%, p = 0.005). CONCLUSIONS Bridging patients to ReTx with ECMO at any time is not advisable. Bridging patients with MCS to ReTx within 1 year of primary cardiac Tx is not advisable. Survival after ReTx for patients bridged by VAD has improved considerably over time. Patients who survive the first year after cardiac Tx can be bridged by VAD to ReTx with an expectation that outcomes can be similar to ReTx patients who did not require MCS.