John G. Coles

ABO-Incompatible heart transplantation in infants

BACKGROUND Transplantation of hearts from ABO-incompatible donors is contraindicated because of the risk of hyperacute rejection mediated by preformed antibodies in the recipient to blood-group antigens of the donor. This contraindication may not apply to newborn infants, who do not yet produce antibodies to T-cell-independent antigens, including the major blood-group antigens. METHODS We studied 10 infants 4 hours to 14 months old (median, 2 months) who had congenital heart disease or cardiomyopathy and who received heart transplants from donors of incompatible blood type between 1996 and 2000. Serum isohemagglutinin titers were measured before and after transplantation. Plasma exchange was performed during cardiopulmonary bypass; no other procedures for the removal of antibodies were used. Standard immunosuppressive therapy was given, and rejection was monitored by means of endomyocardial biopsy. The results were compared with those in 10 infants who received heart transplants from ABO-compatible donors. RESULTS The overall survival rate among the 10 recipients with ABO-incompatible donors was 80 percent, with 2 early deaths due to causes presumed to be unrelated to ABO incompatibility. The duration of follow-up ranged from 11 months to 4.6 years. Two infants had serum antibodies to antigens of the donors blood group before transplantation. No hyperacute rejection occurred; mild humoral rejection was noted at autopsy in one of the infants with antibodies. No morbidity attributable to ABO incompatibility has been observed. Despite the eventual development of antibodies to antigens of the donors blood group in two infants, no damage to the graft has occurred. Because of the use of ABO-incompatible donors, the mortality rate among infants on the waiting list declined from 58 percent to 7 percent. CONCLUSIONS ABO-incompatible heart transplantation can be performed safely during infancy before the onset of isohemagglutinin production; this technique thus contributes to a marked reduction in mortality among infants on the waiting list.

Evolving strategies and improving outcomes of the modified Norwood procedure: a 10-year single-institution experience

BACKGROUND This study reviews our 10-year experience with the modified Norwood procedure to determine its early and midterm outcomes. The focus is on the impact of evolving management strategies and accumulated institutional experience. METHODS A modified Norwood operation was performed in 171 infants over a 10-year period. Sixty-eight percent of the infants were male, the median age at operation was 6 days (range 1 to 175 days), and the median weight was 3.3 kg (range 1.7 to 4.8 kg). The 10-year period was divided into three eras: era I; 1990 through 1993; era II; 1994 through 1997; and era III; 1998 into 2000. Outcomes and risk factors for mortality were sought. RESULTS Hypoplastic left heart syndrome or a variant was the primary diagnosis in 118 infants (69%). The overall 5-year survival rate was 43%. Multivariate analysis revealed that only need of preoperative ventilatory support, earlier date of operation, and lower weight at operation were significant independent predictors of increased time-related mortality. Morphologic features such as a diagnosis other than hypoplastic left heart syndrome, ascending aortic size, and noncardiac anomalies were not significantly associated with an increased risk of death. The hospital survival rate for stage-one palliation in era III was 82%, significantly better than that in the preceding eras (p < 0.001). Attrition between stages one and two accounted for a 15% mortality rate among hospital survivors. CONCLUSIONS With increasing experience and improvements in perioperative care and surgical technique, good outcomes can be expected for the first-stage modified Norwood procedure. Greater monitoring of patients in the interstage period may reduce interval mortality and improve overall survival.

Scimitar syndrome: Twenty years' experience and results of repair

BACKGROUND Thirty-two patients with scimitar syndrome were seen in the period between 1975 and 1995. There were 11 male and 21 female patients. Median age at diagnosis was 7 months (mean 7.7 years, range 1 day to 70 years). Patients in whom the diagnosis was made during the first year of life (infantile group, n = 19) had more severe symptoms and had a higher incidence of heart failure (11/19 vs 0/13) and of pulmonary hypertension (11/19 vs 1/13) than did the patients in whom the diagnosis was made after age 1 year (adult group, n = 13). In 17 patients the anomalous pulmonary venous drainage was repaired by baffling the vein to the left atrium. The median age at this operation was 5.8 years (mean 14.8 years, range 6 months to 70 years). RESULTS No deaths occurred in this surgical group during a mean follow-up period of 8.9 years (range 1.6 to 17 years). Eight patients (47%), however, had evidence of pulmonary venous stenosis after repair, and two required reoperation for pulmonary venous obstruction. All six children in the infantile group had postoperative pulmonary venous stenosis, compared with two of 11 older patients. Postoperative quantitative pulmonary perfusion scans performed in 15 patients demonstrated reduced flow to the right lung (24%, range 0% to 59%). CONCLUSION We conclude that age at detection of scimitar syndrome is important in predicting outcome. Surgical repair seldom results in normal blood flow to the right lung but abolishes left-to-right shunt. Postoperative pulmonary venous obstruction is prevalent, especially in the infants.

Pulmonary valve replacement late after repair of tetralogy of Fallot.

BACKGROUND Pulmonary valve incompetence is usually well tolerated after tetralogy of Fallot repair but may result in late progressive right heart failure as manifested by increasing fatigue, dyspnea, and frequently arrhythmias. METHODS All patients who underwent pulmonary valve replacement in our center late after repair of tetralogy of Fallot were reviewed. RESULTS Eighty-five patients had elective pulmonary valve replacement late (median, 9.3 years) after repair. Operative risk was low (1.1%). Ninety percent of survivors are in New York Heart Association class I. Survival 10 years after pulmonary valve replacement is 95%, with 86% of the patients free of reoperation for valve failure. CONCLUSIONS Pulmonary valve replacement is infrequently required after repair of tetralogy of Fallot. Pulmonary valve replacement may be performed electively with little risk; it improves symptoms of right heart failure and provides satisfactory long-term survival with low risk of early valve failure. As the population of patients who have had repair of tetralogy of Fallot ages, pulmonary valve replacement will become a more frequent consideration.

Integrin-Linked Kinase at the Heart of Cardiac Contractility, Repair, and Disease

Recent advances in cardiac physiology identify the integrin-linked kinase (ILK) as an essential molecule regulating cardiac growth, contractility, and repair. A key transducer of biochemical signals initiated at the plasma membrane by cell–matrix interactions, ILK now emerges as a crucial player in mechanotransduction by integrins. Animal models have been particularly instructive in dissecting the cardiac functions of ILK and its associated proteins, such as parvins and PINCH, and have clearly established ILK as a major contributor to cardiac health. ILK gene knockouts in mice, flies, and worms result in early embryonic lethality because of cell adhesion defects and cytoskeletal disorganization. Although widely distributed in mammalian tissues, ILK expression is highest in the heart, and cardiac-specific ablation of ILK causes cardiomyopathy and sudden death in mice. ILK protein complexes are found in the sarcomere, which is the basic contractile unit of myocytes. A natural inactivating mutation in the kinase domain of ILK disrupts ILK protein interactions in the sarcomere, causing a contractile defect in the zebrafish heart. The relatively subtle phenotype of mutant ILK hearts, compared with ILK-ablated hearts, suggests multiple cardiac ILK functions. Cardiac-specific expression of ILK in transgenic mice induces a hypertrophic program, pointing to ILK as a proximal regulator of multiple hypertrophic signal transduction pathways. ILK protein interactions may also be important in mediating postinfarct cell migration and myocardial repair.

Factors Associated With Mortality and Reoperation in 377 Children With Total Anomalous Pulmonary Venous Connection

Background— We sought to determine era-specific changes in the incidence of mortality and reoperation in children with total anomalous pulmonary venous connection. Methods and Results— We reviewed the records of 377 children presenting from 1946 to 2005 with total anomalous pulmonary venous connection. Multivariable parametric regression models determined the incidence and risk factors for death and reoperation after repair. Pulmonary venous connection was supracardiac in 44%, infracardiac in 26%, cardiac in 21%, and mixed in 9%. Pulmonary venous obstruction was present in 48% at presentation, most frequently with infracardiac connection type (P<0.001). In total, 327 patients were repaired (median age, 1.7 months). Overall survival from repair was 65±6% at 14 years, with a current survival of 97%. Significant (P<0.01) incremental risk factors for postrepair death were cardiac connection type, earlier operation year, younger age at repair, use of epinephrine postoperatively, and postoperative pulmonary venous obstruction. More recent operation year was associated with younger age at repair (P<0.001), decreased use of deep hypothermic circulatory arrest (P<0.001), and use of specific drugs postoperatively (P<0.001). Risk-adjusted estimated 1-year survival for a patient repaired at birth with unfavorable morphology in 2005 is 37% (95% CI, 8 to 80) compared with 96% (95% CI, 91 to 99) for a patient with favorable morphology repaired at 1 year of age. Freedom from reoperation was 82±6% at 11 years after repair, with increased risk associated with mixed connection type (P=0.04) and postoperative pulmonary venous obstruction (P<0.001). Conclusions— Mortality after total anomalous pulmonary venous connection repair has decreased but remains highest in young patients and in those with cardiac connection type or pulmonary venous obstruction. Unfavorable anatomic characteristics remain important determinants of postrepair survival despite improved perioperative care.

Iliofemoral arterial complications of balloon angioplasty for systemic obstructions in infants and children.

The medical and radiological records of 64 consecutive infants and children who underwent transfemoral balloon dilation of the aorta or aortic valve were reviewed to determine the incidence, nature, and post-treatment outcome of acute iliofemoral complications. Balloon dilation angioplasty or balloon valvotomy was performed with 8F and 9F catheters without an arterial sheath. Patients ranged in age from 5 days to 15.4 years (mean, 6.4 years). Of 64 patients, 29 (45.3%) had an acute iliofemoral complication, including thrombosis (18 of 64), complete disruption (five of 64), incomplete disruption (three of 64), and arterial tear (three of 64). The arterial pathology was confirmed in 23 of 29 patients by one or a combination of surgical exploration and repair (18 of 29), angiography (six of 29), and magnetic resonance imaging (three of 29). Of eight patients, three with arterial disruption had acute hypotension requiring transfusion and immediate surgery; the other five had absent pedal pulses after the procedure. Of these five, three developed bleeding during thrombolytic therapy and underwent surgical exploration, and two were diagnosed by angiography after ineffective thrombolytic therapy. Angiography in three patients with iliac artery avulsion showed tapered occlusion in two and an aneurysm in one. In patients with iliofemoral thrombosis, angiography showed occlusion from the puncture site to the origin of the external iliac artery. Eleven patients (17% of the entire group and 38% of the group with acute iliofemoral complications) had reduced or absent pedal pulses at the time of discharge. A significant correlation was found between increased incidence of iliofemoral thrombosis and disruption (as well as abnormal pedal pulses at hospital discharge) and low patient weight.

A sutureless technique for the relief of pulmonary vein stenosis with the use of in situ pericardium.

Pulmonary vein (PV) stenosis develops as a progressive and usually lethal complication after surgical repair of total anomalous PV connection. Conventional surgical repair for the management of recurrent PV stenosis has been generally unsuccessful because of proliferative neointimal hyperplasia resulting in recurrent PV obstruction. The factors that result in recurrent stenosis after the usual types of patch venoplasty are unknown. We speculated that direct suturing of PVs and patch material may be the substrate for turbulent blood flow triggering intimal hyperplasia and eventual narrowing of the vein. On the basis of these considerations, we developed a sutureless technique for repairing PV stenosis with in situ pericardium. We present here its early but promising results. Patients PATIENT 1. Patient 1 was born in January 1995 with infradiaphragmatic total anomalous PV connection and severe obstruction of the descending vertical vein. On day 1, the infradiaphragmatic anomalous vein was ligated and the confluence was anastomosed to the left atrium under conditions of hypothermic circulatory arrest. At 6 months, the child had conspicuous tachypnea. Echocardiography revealed obstructed left PVs with a mean gradient of 7 mm Hg (peak 16 mm Hg) and suprasystemic right ventricular pressure. Angiocardiography demonstrated variable obstruction of all four PVs, with a mean pulmonary artery pressure of 38 mm Hg (systolic 92 mm Hg). At reoperation, obstruction of all PVs was confirmed. Under conditions of circulatory arrest, a pedicled flap of free right atrial wall–superior vena cava junction based at the inferior vena cava was used to patch the right-sided veins and carried behind the aorta to patch the left upper PV. The left lower vein was repaired with a flap created from the left atrial appendage. After that operation, the child had repeated admissions with respiratory tract infections, complicated at 1 year by hemoptysis. Echocardiography revealed recurrence of obstruction. At the second reoperation, atretic left-sided veins and severe stenosis of right-sided veins were noted. The PVs were opened, and an in situ pericardial sutureless patch was used for reconstruction. Echocardiography a year later showed patent veins, with mean gradients of 4 mm Hg on the right side and 5 mm Hg on the left. The estimated mean pulmonary artery pressure was 10 mm Hg. Perfusion lung scan showed 67% perfusion on the right side and 33% on the left. The child currently has no symptoms. PATIENT 2. Patient 2, a female infant, was born on January 1995 with total anomalous PV connection to coronary sinus with echocardiographic evidence of partial obstruction. At 2 weeks, she underwent repair consisting of unroofing of the coronary sinus, as described by Van Praagh and Harken. On completion of the procedure, the patient could not be weaned from cardiopulmonary bypass. At this time the right ventricular pressure was suprasystemic. The child was placed on extracorporeal membrane oxygenator and subsequently weaned after 3 days, with delayed sternal closure in 10 days as a result of persistent hemodynamic instability. Echocardiographic findings before discharge revealed unobstructed PV confluence–left atrium connection. However, echocardiography 4 months later revealed an obstructed right upper PV with a mean right ventricular pressure of 25 mm Hg. Perfusion scan showed 87% perfusion to the left lung and 13% to the right. Eleven months after the operation, echocardiography and cardiac catheterization revealed pulmonary hypertension, with a mean pulmonary artery pressure of 34 mm Hg and anatomically right PV stenosis. At reoperation, the presence of severe bilateral PV stenosis extending from left atrium a variable distance into the intraparenchymal PVs was confirmed. An in situ pericardial baffle was used for repair, as described here. Cardiac catheterization 6 months later revealed normal venous drainage on the left side and mild obstruction on the right side. The mean pulmonary artery pressure was 16 mm Hg. Perfusion lung scan showed 42% to left lung and 58% to right. The child has no symptoms at 15 months of postoperative follow-up. Technique. Standard cardiopulmonary bypass technique is used. The incision is made into the left atrium and extended into both upper and lower PV ostia separately (Fig. 1, A). This incision can be carried into the secondary, and if necessary, the tertiary branches of both the upper and lower lobe veins to a level at which the intima appears grossly normal. The pericardium overlying the entrance of the PVs is used to create an enlarged communication between the opened PVs and the left atrium. The neoatrium is created by suturing the pericardium to the epicardium of the left atrium, completely circumscribing the opening in the left atrium and PVs so that the PV effluent is contained by pericardium. The reconstruction is From the Division of Cardiovascular Surgery, Department of Surgery, Hospital of Sick Children, and University of Toronto Faculty of Medicine, Toronto, Ontario, Canada.

Long-term results in neonates with pulmonary atresia and intact ventricular septum

Our entire institutional experience with pulmonary atresia and intact ventricular septum (1965 through 1987) included 115 patients, 16 of whom died before surgical intervention. Fifty-six percent of surgical patients (n = 99) had angiographic evidence of right ventricle-coronary arterial connections. The early mortality in the surgical group was 27.2%, and the actuarial survival was 24.7% +/- 6% at 13 years postoperatively. Multivariate analysis indicated that the presence of ventriculocoronary connections (p = 0.037), a decreasing ratio between right ventricular and left ventricular pressure at the initial cardiac catheterization (p = 0.007), and lower weight at operation (p = 0.001) were incremental risk factors for postoperative death; the presence of Ebsteins anomaly was an additional risk factor in the overall experience (including patients not surgically treated) (p = 0.01). Nearly all long-term survivors underwent at least one reoperation, including right ventricular outflow tract reconstruction (n = 39) and thromboexclusion of the right ventricle (n = 9). The presence of severe stenosis or interruption of the proximal left anterior descending coronary artery system was a uniformly lethal risk factor for patients undergoing these procedures (p = 0.0003). We conclude that surgical procedures that successfully decompress the right ventricle will usually result in biventricular circulation in and long-term survival of patients with pulmonary atresia with intact ventricular septum not complicated by Ebsteins anomaly or extensive ventriculocoronary connections. Decompression or thromboexclusion of the right ventricle is contraindicated in patients with ventriculocoronary connections and a right ventricle-dependent coronary circulation.

Intraoperative Detection of Spinal Cord Ischemia Using Somatosensory Cortical Evoked Potentials during Thoracic Aortic Occlusion

Paraplegia remains a devastating and unpredictable complication of surgical procedures requiring temporary occlusion of the thoracic aorta, interruption of important spinal radicular vessels, or both. Intraoperative monitoring of the physiological integrity of the spinal cord should permit the early detection of spinal cord ischemia, the judicious and timely institution of corrective measures, including bypass or shunting, and the preservation of important intercostal arteries in appropriate circumstances. A model of spinal cord ischemia was created by temporary proximal and distal occlusion of the canine thoracic aorta. Serial measurement of somatosensory cortical evoked potentials (SCEP) generated by peripheral nerve stimulation, reflecting the status of long-tract neural conduction, was used to monitor alterations in spinal cord function during ischemia. Twelve animals subjected to aortic occlusion demonstrated a characteristic time-related deterioration of the SCEP with virtual extinction of the signal at a mean interval (+/- standard error of the mean) of 12.4 +/- 1.5 minutes. Six animals in which reperfusion was established immediately following the loss of the SCEP (Group 1) demonstrated complete recovery without neurological sequelae, as assessed by clinical and histological criteria. In 6 animals (Group 2), the period of aortic occlusion was extended for an additional 15 minutes following loss of the SCEP (27.3 +/- 2.3 minutes); postoperatively, 4 of 6 animals sustained major neurological lesions characterized by spastic paraplegia and histological evidence of spinal cord infarction (Group 1 versus Group 2, p less than 0.05). We conclude that distinctive alterations in the SCEP are indicative of reversible ischemic spinal cord dysfunction. On-line monitoring of spinal cord function using the technique of SCEP provides a rational basis for determining of SCEP provides a rational basis for determining operative strategy during surgical procedures on the thoracic aorta.