Sanjiv K. Gandhi

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

BACKGROUNDnBeginning 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.nnnMETHODSnBetween 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.nnnRESULTSnMedian age and weight at VAD implant were 2.1 years (range, 12 days-17.8 years) and 11 kg (range, 3-87.6 kg), respectively. The primary diagnoses were dilated cardiomyopathy in 42 (58%), congenital heart disease in 19 (26%), myocarditis in 7 (10%), and other cardiomyopathies in 5 (7%). Pre-implant clinical condition was critical cardiogenic shock in 38 (52%), progressive decline in 33 (45%), or other in 2 (3%). Extracorporeal membrane oxygenation was used as a bridge to EXCOR in 22 patients (30%). Device selection was left VAD (LVAD) in 42 (57%) and biventricular assist devices (BiVAD) in 31 (43%). The EXCOR bridged 51 patients (70%) to transplant and 5 (7%) to recovery. Mortality on the EXCOR was 23% (n = 17) overall, including 35% (11 of 31) in BiVAD vs 14% (6 of 42) in LVAD patients (p = 0.003). Multivariate analysis showed younger age and BiVAD support were significant risk factors for death while on the EXCOR.nnnCONCLUSIONSnThis 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.

Biventricular Assist Devices as a Bridge to Heart Transplantation in Small Children

Background— Experience with the use of biventricular assist device (BiVAD) support to bridge small children to heart transplantation is limited. Methods and Results— We used BIVAD support (Berlin EXCOR) in 9 pediatric heart transplant candidates from 4/05 to 7/07. The median patient age was 1.7 years (12 days to 17 years). The median patient weight was 9.4 kg (3 to 38 kg). All children were supported with multiple intravenous inotropes±mechanical ventilation (6) or ECMO (3) before BiVAD implantation. All had significant right ventricular dysfunction. The median pulmonary vascular resistance index (Rpi) was 6.0 WU/m2. Eight patients were successfully bridged to heart transplantation after a median duration of BiVAD support of 35 days (1 to 77 days). One death occurred after 10 days of support from perioperative renal failure in a 3 kg infant. Five patients required at least 1 blood pump change. One patient had a driveline infection requiring treatment. There were no acute neurological complications, no thromboembolic events, and no bleeding complications. In 2 patients with Rpi >10 WU/m2 unresponsive to pulmonary vasodilator therapy, Rpi dropped to 1.4 and 4.6 WU/m2, after 33 and 41 days of support, respectively. All 8 survivors underwent successful heart transplantation. Of 5 patients supported >30 days, 3 developed an extremely elevated (>90%) panel reactive antibody by ELISA that was not confirmed by other methods; none had a positive donor-specific retrospective crossmatch. There was 1 episode of rejection (with hemodynamic compromise) in the 8 transplanted patients. Rpi was normal (<3 WU/m2) without pulmonary vasodilators in all patients within 3 months after transplant. There have been no deaths after transplant with a median follow-up of 19 months. Conclusions— BiVAD support can effectively be used in small children as a bridge to heart transplantation and can be accomplished with low mortality and morbidity. BiVAD support may offer an additional means to reverse extremely elevated pulmonary vascular resistance. Surveillance for HLA antibody sensitization during BiVAD support may be complicated by the development of non-HLA antibodies which may not reflect true HLA presensitization.

Lateral tunnel suture line variation reduces atrial flutter after the modified Fontan operation

BACKGROUNDnAtrial flutter (AFL) is a common postoperative sequela of the modified Fontan operation, or total cavopulmonary connection. We hypothesized that injury to the crista terminalis (CT) by the lateral tunnel suture line contributes to the development of AFL in this setting. This study was designed to determine the effects of alteration of the lateral tunnel suture line, relative to the CT, on the inducibility of AFL in an acute canine model of the modified Fontan operation.nnnMETHODSnAdult mongrel dogs (n = 25) underwent a median sternotomy and normothermic cardiopulmonary bypass. In groups 1, 2, and 3, through a right atriotomy, a suture line was placed to simulate the lateral tunnel of the modified Fontan operation (n = 20). The lateral aspect of the suture line ran along the CT in group (n = 10), 5 mm medial to the CT in group 2 (n = 5), and 10 mm anterior to the CT, incorporated into the atriotomy closure, in group 3 (n = 5). In group 4 (n = 5), only the lateral portion of the suture line, along the CT, was placed. Form-fitting 253-point unipolar endocardial mapping electrodes were inserted in the left and right atria via bilateral ventriculotomies. Induction of AFL was then attempted using atrial burst pacing. If sustained AFL could not be induced, isoproterenol was administered and the pacing protocol repeated. Endocardial activation sequence maps of spontaneous rhythm and AFT were constructed.nnnRESULTSnUnder baseline conditions, after placement of the suture line, sustained AFL could reproducibly be induced in 8/10 dogs in group 1, 0/5 dogs in group 2, 0/5 dogs in group 3, and 5/5 dogs in group 4 (p < 0.001). After isoproterenol administration, sustained AFL was reproducibly inducible in the remaining 2 dogs in group 1, 4/5 dogs in group 2, and 0/5 dogs in group 3 (p = 0.01). The mean cycle length of AFL was 189 +/- 25 ms in group 1, 136 +/- 8 ms in group 2, and 182 +/- 20 ms in group 4 (p < 0.001). Atrial activation sequence maps, during sinus rhythm, demonstrated a line of conduction block along the lateral portion of the suture line in all cases in groups 1 and 4 and in only those cases in group 2 in which sustained AFL was inducible. During AFL this block facilitated unidirectional conduction, permitting propagation of the reentrant wavefront. Mean conduction velocity along the CT during sinus rhythm was 0.63 +/- 0.10 m/s in group 1, 1.04 +/- 0.17 m/s in group 2, 1.01 +/- 0.12 m/s in group 3, and 0.44 +/- 0.13 m/s in group 4 (p < 0.01).nnnCONCLUSIONSnIn an acute canine model of the modified Fontan operation, conduction block imposed by the lateral tunnel suture line is an essential component of the AFL circuit. The inducibility of AFL is increased by suture line placement along the CT. Slow conduction, resulting from injury to the CT, promotes this increased inducibility. Avoidance of the CT may reduce the incidence of AFL in children undergoing the modified Fontan operation.

Trends in the indications and survival in pediatric heart transplants: a 24-year single-center experience in 307 patients.

BACKGROUNDnHeart transplantation is the only viable treatment for children with end-stage heart failure due to congenital heart disease (CHD) or cardiomyopathy. This study reviewed the trends in the indications for transplant and survival after transplant during the past 24 years.nnnMETHODSnA retrospective review was performed of the 307 heart transplants performed at our center since 1986. To analyze the trends in the indications for transplant as well as operative death and late-survival, the data were divided into three periods in 8-year increments: 1986 to 1993 (50 patients), 1994 to 2001 (116 patients), and 2002 to 2009 (141 patients).nnnRESULTSnThe indications for transplantation were 39% cardiomyopathy, 57% CHD, and 4% retransplant. Of the 173 with CHD, 139 (80%) had single-ventricle (SV) anomalies. In the CHD group, transplantation for failed SV palliation, including Fontan procedure, became the predominant indication in the last 8-year interval of our program. Survival after transplant was the best in patients with cardiomyopathy and the worst in patients with failed palliations for SV anomalies, including failed Fontan procedures.nnnCONCLUSIONSnTransplantation for heart failure related to failed SV palliation has become the most common indication for patients with CHD. The high-risk nature of these transplants will have significant implications for heart transplant programs as more infants with SV anomalies survive palliative procedures performed during infancy.

Extracorporeal membrane oxygenation in pediatric lung transplantation.

OBJECTIVEnEffectiveness of preoperative and postoperative extracorporeal membrane oxygenation support in pediatric lung transplantation was studied.nnnMETHODSnInstitutional database of pediatric lung transplants from 1990 to 2008 was reviewed.nnnRESULTSnThree hundred forty-four patients underwent lung transplants in the study period. Thirty-three of 344 patients (9.6%) required perioperative extracorporeal membrane oxygenation support. Fifteen patients (median, age 1.3 years; range, 0.2-18 years) required 16 pretransplant extracorporeal membrane oxygenation runs. Indications were respiratory failure (8/16, 50%), severe pulmonary hypertension (5/16, 31%), and cardiopulmonary collapse (3/16, 19%). Four of these patients (27%) also required postoperative support. Six (40%) were weaned before lung transplant. Six (40%) survived to hospital discharge. Survival to discharge was higher among patients weaned before lung transplant (4/6, 66% vs 2/9, 22%). Twenty-two patients (median age, 9.4 years; range, 0.2-21 years) underwent 24 extracorporeal membrane oxygenation runs after lung transplant. Indications for postoperative support were primary graft dysfunction (18/24, 75%), pneumonia (4/24, 16%), and others (2/24, 9%). Median time between lung transplant and institution of extracorporeal membrane oxygenation was 32 hours (range, 0-1084 hours); median duration of support was 141 hours (range, 48-505 hours). Five of these patients (23%) survived to hospital discharge. Among nonsurvivors, causes of death were intractable respiratory failure (12/17, 70%) and infectious complications (4/17, 24%).nnnCONCLUSIONSnNeed for perioperative extracorporeal membrane oxygenation support is associated with significant morbidity and mortality among pediatric patients receiving lung transplants. A subset of patients who can be weaned from support preoperatively have greater likelihood of survival.

Characterization and surgical ablation of atrial flutter after the classic fontan repair

BACKGROUNDnAtrial flutter (AFL) is a frequent postoperative complication of the classic Fontan operation, which uses an atriopulmonary connection. We hypothesized that the suture lines alone, in the absence of any hemodynamic alterations, provide the necessary electrophysiologic substrates for AFL. The objectives of this study were to determine if the Fontan suture lines alone are sufficient to permit sustained AFL in an acute canine model and to characterize any resulting reentrant circuits to surgically ablate the AFL.nnnMETHODSnAfter cardiopulmonary bypass, adult dogs (n = 18) underwent a simulated classic Fontan operation. This included a longitudinal right atriotomy and an incision from the base of the right atrial appendage toward the dome of the left atrium, representing the atriopulmonary connection. In 6 of 18 dogs, an atrial septal defect was created at the level of the fossa ovalis. Unipolar 253-point biatrial endocardial mapping electrodes were placed via bilateral ventriculotomies. Induction of AFL was attempted by atrial burst pacing. If AFL could not be induced, isoproterenol was administered and pacing repeated. Activation sequence maps of the pathways of atrial reentry were generated. In 8 dogs with inducible AFL, an incision was made from the atriotomy to the atriopulmonary connection and burst pacing repeated.nnnRESULTSnSustained AFL could not be induced after bypass alone in any case. After the simulated Fontan operation, sustained AFL was reproducibly induced in all 18 dogs, 6 of which required isoproterenol. The mean cycle length of all cases was 177 +/- 20 ms. During AFL, atrial activation sequence maps demonstrated lines of conduction block created by both the atriotomy and the atriopulmonary connection. The isthmus of tissue between these two lines of block was essential for propagation of the reentrant wavefront. Interruption of this isthmus with an incision successfully terminated AFL in 8 of 8 dogs.nnnCONCLUSIONSnIn an acute canine model, the Fontan suture lines alone, in the absence of atrial hypertension or stretch, permit the induction of AFL. An essential electrophysiologic substrate is an isthmus of myocardium between the atriotomy and the atriopulmonary connection. Interruption of conduction through this isthmus terminates the AFL in this model and suggests a technique for ablation of AFL in patients who have undergone a classic Fontan operation.

Lung Transplantation in Infants and Toddlers from 1990 to 2004 at St. Louis Children's Hospital

In a retrospective, single‐center cohort study, outcomes of infants and toddlers undergoing lung transplant at St. Louis Childrens Hospital between 1990 and 2004 were compared to older children. Patients with cystic fibrosis (exclusively older children) and those who underwent heart–lung, liver–lung, single lung or a second transplantation were excluded from comparisons. One hundred nine lung transplants were compared. Thirty‐six were in infants <1 year old, 26 in toddlers 1–3 years old and 47 in children >3 years old. Graft survival was similar for infants and toddlers (p = 0.35 and p = 0.3, respectively) compared to children over 3 years old at 1 and 3 years after transplant. Significantly more infants (p < 0.0001 and p = 0.003) and toddlers (p = 0.002 and p = 0.03) were free from acute rejection and bronchiolitis obliterans compared to older patients. While most infants and toddlers had only minimal lung function impairment, and achieved normal to mildly delayed developmental scores, somatic growth remained depressed 5 years after transplant. Lung transplantation in infants and young children carries similar survival rates to older children and adults. Further insights into the unique immunologic aspects of this group of patients may elucidate strategies to prevent acute and chronic rejection in all age groups.

ANATOMICALLY BASED ABLATION OF ATRIAL FLUTTER IN AN ACUTE CANINE MODEL OF THE MODIFIED FONTAN OPERATION

BACKGROUNDnLateral tunnel total cavopulmonary connection, also called the modified Fontan operation, uses a baffle through the right atrium. We established, in an acute canine model, that atrial flutter after total cavopulmonary connection revolves around a line of conduction block imposed by the free wall lateral tunnel suture line. We hypothesized that a line of conduction block between the free wall total cavopulmonary connection suture line and the tricuspid anulus would interrupt atrial flutter in this model.nnnOBJECTIVEnOur objective was to determine whether a cryolesion placed between the free wall total cavopulmonary connection suture line and the tricuspid anulus would terminate atrial flutter in an acute canine model.nnnMETHODSnSeven adult dogs underwent median sternotomy and institution of cardiopulmonary bypass. A suture line was placed through a right atriotomy to simulate total cavopulmonary connection lateral tunnel construction. Form-fitting 253-point biatrial endocardial mapping electrodes were placed via bilateral ventriculotomies. Atrial flutter was induced by atrial burst pacing. A cryothermal lesion was then placed between the free wall total cavopulmonary connection suture line and the tricuspid anulus in the low lateral right atrium (i.e., CRYO 1 procedure), and reinduction of atrial flutter was attempted. If atrial flutter was reinduced, the cryolesion was modified superiorly to include the caudal portion of the atriotomy (i.e., CRYO 2 procedure). Activation sequence maps were generated for sinus rhythms before and after the cryolesions were placed and for induced arrhythmias.nnnRESULTSnIn all seven cases, atrial flutter was inducible after suture line placement, before placement of a cryolesion. The reentrant circuit incorporated both caval orifices in five of seven cases and was successfully ablated by the CRYO 1 approach in each case. Atrial flutter was not inducible after placement of the CRYO 2 lesion in the remaining two cases, in which breakthrough of the wave front occurred across the lateral tunnel suture line in the intercaval region. Activation sequence maps of sinus rhythm after placement of the cryolesions demonstrated a conduction block at the site of the lesion.nnnCONCLUSIONSnA linear cryothermal lesion placed between the free wall aspect of the total cavopulmonary connection suture line and the tricuspid anulus created a line of conduction block that successfully ablates atrial flutter in the canine model.

Infectious, Malignant, and Autoimmune Complications in Pediatric Heart Transplant Recipients

OBJECTIVEnTo review clinical courses of pediatric heart transplant survivors after 5 years from transplantation for infections, lymphoproliferative, and autoimmune diseases.nnnSTUDY DESIGNnA total of 71 patients were examined in 2 groups, infant recipients (underwent transplant <1 year of age, n = 38) and older recipients (underwent transplant >1 year, n = 33). All patients received comparable immunosuppression. Calculated occurrence rates were reported as means per 10 years of follow-up with SEs. Differences were examined by using Poisson regression.nnnRESULTSnInfant recipients had significantly higher (P < .001) occurrence rates of severe (mean, 2.04 +/- 0.5) and chronic infections (mean, 4.58 +/- 0.67) compared with older recipients (means, 0.37 +/- 0.19 and 1.87 +/- 0.70, respectively). Types of infections were similar to those in the general population with extremely rare opportunistic infections; however, they were more severe and resistant to treatment. Autoimmune disorders occurred at a frequency comparable with lymphoproliferative diseases and were observed in 7 of 38 infants (18%). Most common were autoimmune cytopenias.nnnCONCLUSIONSnInfant heart transplant recipients who survive in the long term have higher occurrence rates of infections compared with older recipients. Autoimmune disorders are a previously unrecognized morbidity in pediatric heart transplantation.

A canine model of atrial flutter following the intra-atrial lateral tunnel fontan operation

Atrial flutter (AFL) is a common problem in children who have undergone a Fontan operation for single ventricle physiology. Although this has been attributed to the atrial stretch inherent in the earlier forms of this operation, AFL has persisted in spite of a modification that minimizes atrial distension. Therefore, it was hypothesized that AFL following the modified Fontan procedure may result from anatomic barriers related to suture lines rather than from atrial stretch or hypertension. In a series of experiments performed in dogs under general anesthesia, the modified Fontan repair was simulated by placing only the suture line of the intra-atrial repair. No baffle was placed, thus avoiding any hemodynamic alterations. After closure of the atriotomy, 253 point unipolar atrial endocardial form-fitting electrodes were inserted through the mitral and tricuspid valves via bilateral ventriculotomies. Induction of AFL was attempted with atrial burst pacing and programmed extrastimulation, and activation sequence maps of subsequent reentry were generated from the endocardial electrodes. Atrial flutter was induced in all of 17 dogs, with a median cycle length of 177 +/- 31 ms. Activation sequence maps demonstrated conduction block along the crista terminalis corresponding to the free wall portion of the suture line. This created an isthmus between the suture line and tricuspid annulus, which appeared critical for sustaining AFL, although the circuit used both the septal and free wall surfaces of the right atrium. In seven dogs, a cryolesion was placed from the tricuspid annulus to the free wall segment of the suture line, terminating the AFL, in all seven. When the free wall segment of the suture line was moved 5 mm medial to the crista terminalis, AFL was induced in four of five dogs, but only in the presence of isoproterenol and at a shorter cycle length (136 +/- 8 ms, P < .001). Atrial flutter was not inducible, even with the addition of isoproterenol, in any of five dogs in which the suture line was placed 10 mm anterior to the crista terminalis and incorporated into closure of the atriotomy. This acute canine model of the modified Fontan operation demonstrates that conduction block from the free wall portion of the suture line creates an isthmus of tissue between the suture line and the tricuspid annulus. This is a sufficient substrate to produce AFL; no hemodynamic alteration is required. Injury to the crista terminalis is a significant risk factor in this model, which suggests that a modification of the suture line might reduce the incidence of AFL in patients following this operation.