Randall L. Caldwell

Surgical management of complete atrioventricular septal defects: A twenty-year experience

Creation of a competent left atrioventricular valve is a cornerstone in surgical repair of complete atrioventricular septal defects. To identify risk factors for mortality and failure of left atrioventricular valve repair and to determine the impact of cleft closure on postoperative atrioventricular valve function, we retrospectively analyzed hospital records of 203 patients between January 1974 and January 1995. Overall early mortality was 7.9%. Operative mortality decreased significantly over the period of the study from 19% (4/21) before 1980 to 3% (2/67) after 1990 (p = 0.03). Ten-year survival including operative mortality was 91.3% +/- 0.004% (95% confidence limit): all survivors are in New York Heart Association class I or II. Preoperative atrioventricular valve regurgitation was assessed in 203 patients by angiography or echocardiography and was trivial or mild in 103 (52%), moderate in 82 (41%), and severe in 18 (8%). Left atrioventricular valve cleft was closed in 93% (189/203) but left alone when valve leaflet tissue was inadequate and closure of the cleft might cause significant stenosis. Reoperation for severe postoperative left atrioventricular valve regurgitation was necessary in eight patients, five of whom initially did not have closure of the cleft and three of whom had cleft closure. Six patients had reoperation with annuloplasty and two patients required left atrioventricular valve replacement. Five patients survived reoperation and are currently in New York Heart Association class I or II. On most recent evaluation assessed by angiography or echocardiography (a mean of 59 months after repair), left atrioventricular valve regurgitation was trivial or mild in 137 of the 146 survivors (94%) examined; none had moderate or severe left atrioventricular valve stenosis. By multiple logistic regression analysis, strong risk factors for early death and need for reoperation included postoperative pulmonary hypertensive crisis, immediate postoperative severe left atrioventricular valve regurgitation, and double-orifice left atrioventricular valve. These results indicate that complete atrioventricular septal defects can be repaired with low mortality and good intermediate to long-term results. Routine approximation of the cleft is safe and has a low incidence of reoperation for left atrioventricular valve regurgitation.

Acute Doxorubicin Cardiotoxicity Is Associated With p53-Induced Inhibition of the Mammalian Target of Rapamycin Pathway

Background— Doxorubicin is used to treat childhood and adult cancer. Doxorubicin treatment is associated with both acute and chronic cardiotoxicity. The cardiotoxic effects of doxorubicin are cumulative, which limits its chemotherapeutic dose. Free radical generation and p53-dependent apoptosis are thought to contribute to doxorubicin-induced cardiotoxicity. Methods and Results— Adult transgenic (MHC-CB7) mice expressing cardiomyocyte-restricted dominant-interfering p53 and their nontransgenic littermates were treated with doxorubicin (20 mg/kg cumulative dose). Nontransgenic mice exhibited reduced left ventricular systolic function (predoxorubicin fractional shortening [FS] 61±2%, postdoxorubicin FS 45±2%, mean±SEM, P<0.008), reduced cardiac mass, and high levels of cardiomyocyte apoptosis 7 days after the initiation of doxorubicin treatment. In contrast, doxorubicin-treated MHC-CB7 mice exhibited normal left ventricular systolic function (predoxorubicin FS 63±2%, postdoxorubicin FS 60±2%, P>0.008), normal cardiac mass, and low levels of cardiomyocyte apoptosis. Western blot analyses indicated that mTOR (mammalian target of rapamycin) signaling was inhibited in doxorubicin-treated nontransgenic mice but not in doxorubicin-treated MHC-CB7 mice. Accordingly, transgenic mice with cardiomyocyte-restricted, constitutively active mTOR expression (MHC-mTORca) were studied. Left ventricular systolic function (predoxorubicin FS 64±2%, postdoxorubicin FS 60±3%, P>0.008) and cardiac mass were normal in doxorubicin-treated MHC-mTORca mice, despite levels of cardiomyocyte apoptosis similar to those seen in doxorubicin-treated nontransgenic mice. Conclusions— These data suggest that doxorubicin treatment induces acute cardiac dysfunction and reduces cardiac mass via p53-dependent inhibition of mTOR signaling and that loss of myocardial mass, and not cardiomyocyte apoptosis, is the major contributor to acute doxorubicin cardiotoxicity.

Survival and risk factors for death after cardiac transplantation in infants: A multi-institutional study

BACKGROUND Despite the increasing application of cardiac transplantation in infants, reported survival rates vary, and risk factors for death are poorly understood. METHODS AND RESULTS To examine early survival and risk factors for death in infants (< 1 year of age) undergoing cardiac transplantation, 141 infants (36 < 1 months of age) underwent primary cardiac transplantation between January 1, 1993, and January 1, 1995, at 23 centers in the Pediatric Heart Transplant Study (PHTS). Diagnoses were hypoplastic left heart syndrome (66%), other congenital heart disease (17%), cardiomyopathy (14%), and other (3%). Actuarial survival after cardiac transplantation was 84% at 1 month, 70% at 1 year, and 69% at 2 years, with the greatest hazard for death within the first 3 months. The principal cause of death was early graft failure in 20 patients (52% of deaths), infection in 10 (26% of deaths), and rejection in 4 (10%). On the basis of multivariate analysis, risk factors for early mortality were history of previous sternotomy (P = .0003), nonidentical blood type donor (P = .01), recipient non-blood group A (P = .02), and donor cause of death other than closed head trauma (P = .04). Diagnosis at listing, waiting time (mean, 1.3 months), graft ischemic time (mean, 228 minutes; range, 68 to 479 minutes), and recipient ventilatory or inotropic support at listing were not predictive for mortality after transplant. CONCLUSIONS The higher mortality rate observed with infant heart transplantation is due to a higher mortality within the first month after transplantation as a result of early graft failure. Strategies to improve donor heart function at implantation would have the greatest impact on survival after infant cardiac transplantation.

Negative contrast echocardiography: a new method for detecting left-to-right shunts.

Cross-sectional echocardiographic visualization of the interatrial septum in both normal persons and patients with atrial septal defects has been reported. Although septal defects can generally be visualized, false positives are frequently encountered. This study evaluated whether visualizing the patterns of contrast flow in the region of an apparent atrial septal defect by cross-sectional echocardiography could aid in the differentiation of true defects from false positives. We studied 25 patients 13 with intact interatrial septa and 12 with atrial septal defects. Contrast was visualized in the right atrium in 24 of 25 patients (all 13 normal patients and 11 of 12 patients with atrial septal defects). In all patients with intact interatrial septum, the peripherally injected contrast material homogenously filled the right atrium, delineating the position and integrity of the interatrial septum. In two of 11 patients with atrial septal defects, evidence of right-to-left shunting through the defect confirmed its presence. In the remaining nine patients, the flow of blood from left atrium to right atrium, following the path of the left-to-right shunt, produced an echo-free area along the right margin of the interatrial septum, or an area of negative contrast. This phenomenon was produced by the non-contrastcontaining blood flowing through the septum and displacing the contrast-containing blood from along the righthand portion of the septum. This study suggests that peripheral injection of echocardiographic contrast material may be of value in detecting atrial septal defects in patients with predominant left-to-right shunting when contrast flows are evaluated using cross-sectional echocardiography.

Indomethacin therapy on the first day of life in infants with very low birth weight

To investigate the optimal timing for treatment of small premature infants, we performed a double-blind, controlled trial of indomethacin therapy on the first day of life in 104 infants weighing between 700 and 1300 gm. Infants were given indomethacin or placebo at a mean age of 15 hours. Eleven of the 56 infants given placebo developed large left-to-right shunts through a patent ductus arteriosus. In contrast, only two of the 51 infants given indomethacin developed large shunts (P less than 0.025). There were no significant differences in incidence of surgical ligation, duration of oxygen therapy, duration of endotracheal intubation, days required to regain birth weight, or incidence of complications. However, the power of the tests of significance was low because of the small number of patients. Thus, although the incidence of large left-to-right ductus shunts was decreased in the indomethacin group, morbidity was not otherwise altered for the entire group of patients, possibly because of the relatively low incidence (21%) of large shunts in the placebo group. We conclude that although treatment with indomethacin on the first day of life appears to be safe, there is little advantage to its use in centers where the incidence of large shunts through a patent ductus arteriosus is relatively low.

Cor Triatriatum: Clinical Presentation and Surgical Results in 12 Patients

Twelve patients with cor triatriatum have been seen at our institution since 1979. The clinical presentation, diagnostic evaluation, and surgical results are outlined in this retrospective review. Operation is the treatment of choice for this rare congenital cardiac defect. One patient died 1 day before scheduled operation, and 2 patients died postoperatively, yielding a surgical mortality rate of 17% and an overall mortality rate of 25%. Resection of the obstructing atrial membrane was performed using hypothermic cardiopulmonary bypass in all cases. Left atriotomy was performed in 6 patients, and right atriotomy was performed in 7. The two postoperative deaths occurred in patients who had serious associated cardiac defects. Associated anomalies include atrial septal defect, persistent left superior vena cava, and partial anomalous pulmonary venous return. The postoperative course has been excellent in all 9 surviving patients; all remain asymptomatic. Cor triatriatum is amenable to surgical repair with excellent results when diagnosed early and when not complicated by other severe cardiac anomalies.

Surgical management of hypoplastic left heart syndrome

BACKGROUND The treatment of infants with hypoplastic left heart syndrome has been challenging and controversial. METHODS To assess the operative management and intermediate-term outcome, we retrospectively analyzed our surgical experience with 50 newborns with hypoplastic left heart syndrome operated on between January 1989 and June 1995. RESULTS Surgical palliation with a first-stage Norwood operation was offered to 28 patients. The remaining 22 infants were initially listed for heart transplantation, and 15 underwent the operation. Ten of the 15 recipients are alive, and all are in New York Heart Association class I. Seven infants underwent a Norwood procedure after being on the list for transplantation for 12 to 42 days. A total of 34 patients underwent Norwood procedures with one operation aborted because of inoperable anatomy. Two infants who survived the first-stage Norwood operation underwent subsequent heart transplantation and are currently doing well. The 1-year mortality rate for heart transplantation was 18% (3/17) versus 50% (17/34) for the Norwood procedure. Risk factors for early mortality after a Norwood procedure include longer circulatory arrest time (> 50 minutes), preoperative acidosis (pH < 7.20), larger systemic-pulmonary artery shunt (> or = 4 mm), diminutive ascending aorta (< or = 2.0 mm), and anatomic subtype of aortic and mitral atresia. The 1-year survival rate for the Norwood procedure improved from 36% for the patients operated on during 1989 through 1992 to 75% during 1993 to mid-1995 (p = 0.005). Of the 17 survivors of a first-stage Norwood operation, 10 have undergone the second stage (bidirectional Glenn procedure), and 7 have completed a Fontan procedure. Heart transplantation results have also improved, with no deaths since 1992. CONCLUSIONS Both the Norwood procedure and heart transplantation have encouraging early to intermediate results in infants with hypoplastic left heart syndrome. Hypoplastic left heart syndrome should be managed selectively on the basis of cardiac morphology, donor availability, and family wishes. Development of a flexible program involving the use of both procedures may aid in the successful management of infants with hypoplastic left heart syndrome.

Heparinization for prevention of thrombosis following pediatric percutaneous arterial catheterization.

SummaryOne thousand three hundred and sixteen consecutively catheterized infants and children were evaluated prospectively for femoral artery thrombosis following percutaneous cardiac catheterization. One hundred units/kg heparin bolus was given to 649 patients after arterial puncture (group A). A supplementary 50 units/kg of heparin bolus was given to 381 patients 75 minutes later, followed by a continuous heparin infusion if pulses were decreased (group B). Two hundred forty-one patients were managed similarly except the first supplementary bolus was given 45 minutes after initial heparinization, if necessary, and the second bolus and continuous infusion were begun 45 minutes later, if necessary (group C). Arterial thrombosis was diagnosed if pulses were not equal to those of the unused extremity 6 hours following catheterization.The overall incidence of arterial thrombosis was 0.8%. No statistically significant (p<.05) differences occurred related to the heparinization method used. However, absence of thrombosis in the last 241 consecutive patients (group C) and in the last 480 patients of groups B and C weighing more than 10 kg approaches significance (p<.1). Incidence of thrombosis was less than in previous studies (p<.0005 to .05). This study indicates that a very low incidence of arterial thrombosis can be achieved with systemic heparinization.

Right ventricular systolic function in adolescents and young adults after mustard operation for transposition of the great arteries

This study evaluates long-term ( > 10 years since surgery) right ventricular (RV) systolic function in patients who had previously undergone intraatrial baffle surgery for transposition of the great arteries. Studies suggest these patients are clinically stable and lead satisfactory lifestyles, but long-term ventricular performance is not known. Radionuclide angiocardiography was used to estimate RV ejection fraction in 58 patients a mean of 14 years after the Mustard operation. Repeat studies were performed in 32 patients. The absolute RV ejection fraction of 0.53 +/- 0.10 in our patients did not differ from normal values. Nine patients had a value < 0.42, placing them > 2 SDs below normal. Repeat RV ejection fraction decreased from 0.54 +/- 0.11 to 0.51 +/- 0.11 (p < 0.1) in 32 patients, and > 0.10 in 6. Thus, RV ejection fraction was abnormal in 9 of 58 patients (16%) evaluated > 10 years after a Mustard operation. Repeat studies demonstrate worsening in at least 6 of 32 patients (19%). These postoperative Mustard patients require continued evaluation, even in the absence of overt symptomatology.

Surgery for discrete subvalvular aortic stenosis: Actuarial survival, hemodynamic results, and acquired aortic regurgitation

Discrete membranous subaortic stenosis (DMSS) accounts for 8 to 30% of congenital left ventricular outflow obstruction. The immediate effectiveness of surgical resection of this discrete obstructing membrane has been well documented, but little has appeared regarding late clinical and hemodynamic follow-up. Fifty-three patients with DMSS underwent operation at our institution from 1957 to 1983. Most (78%) were symptomatic, 79% had left ventricular hypertrophy (LVH) by electrocardiogram, and 92% had roentgenographic evidence of cardiomegaly preoperatively. Catheterization revealed a mean preoperative left ventricular-aortic gradient of 89 mm Hg. Twenty-eight patients had associated aortic insufficiency (AI) on the initial aortogram. Seven patients acquired AI in the interim between the first and second preoperative catheterization. Our patients have been followed for up to 12 years postoperatively. There have been 2 early and 3 late deaths. (Actuarial analysis revealed 5- and 10-year survival of 95% and 83%, respectively.) Seventy-one percent of the previously symptomatic patients noted relief of their preoperative complaints, and 45% of those with LVH had a regression in voltage. Cardiomegaly as determined by chest roentgenogram decreased in 45%. The left ventricular-aortic gradient fell to an average of 35 mm Hg a year postoperatively. Surgical treatment of congenital subvalvular aortic stenosis is effective in reducing the preoperative symptoms and the left ventricular-aortic gradient. It appears that DMSS causes AI.