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Biomedical subjects

S D Colan

Publications and source records attributed to S D Colan.

At least 37 records · Page 2Linked to original sources
PubMed1999

Impaired glucose transporter activity in pressure-overload hypertrophy is an early indicator of progression to failure.

BACKGROUND: Severe hypertrophy and heart failure are important risk factors in cardiac surgery. Early adaptive changes in hypertrophy include increased ventricular mass-to-cavity volume ratio (M/V ratio) and increased dependence on glucose for energy metabolism. However, glucose uptake is decreased in the late stages of hypertrophy when ventricular dilatation and failure are present. We hypothesized that impaired glucose uptake would be evident early in the progression of hypertrophy and associated with the onset of ventricular dilatation. METHODS AND RESULTS: Ten-day-old rabbits underwent banding of the descending aorta. Development of hypertrophy was followed by transthoracic echocardiography to measure left ventricular M/V ratio. Glucose uptake rate, as determined by (31)P-nuclear magnetic resonance spectroscopy measuring 2-deoxyglucose conversion to 2-deoxyglucose-6-phosphate, was measured in isolated perfused hearts obtained from banded rabbits when M/V ratio had increased by 15% from baseline (compensated hypertrophy) and by 30% from baseline (early-decompensated hypertrophy). In age-matched control animals, the rate of glucose uptake was 0.61+/-0.08 micromol x g of wet weight(-1) x 30 min(-1) (mean+/-SEM). With a 15% M/V ratio increase, glucose uptake rate remained at control levels (0.6+/-0.05 micromol x g of wet weight(-1) x 30 min(-1)), compared with hearts with 30% increased M/V ratios, where glucose uptake was significantly lower (0.42+/-0.05 micromol x g of wet weight(-1) x 30 min(-1); P</=0.05). Glucose transporter protein expression was the same in all groups. CONCLUSIONS: Glucose uptake rate is maintained during compensated hypertrophy. However, coinciding with severe hypertrophy, preceding ventricular dilatation, and glucose transporter protein downregulation, glucose uptake is significantly decreased. Because of the increased dependence of the hypertrophied hearts on glucose use, we speculate that this impairment may be a contributing factor in the progression to failure.

Animals↗
PubMed1999

Prognostic significance of clinically silent coronary artery fistulas.

Symptomatic coronary artery fistulas (CAF) are associated with significant morbidity and mortality. With the advent of high-resolution 2-dimensional and color Doppler echocardiography, the detection rate of clinically silent CAF has increased, but their clinical significance and outcome have not been defined. The clinical, echocardiographic, electrocardiographic, and angiographic findings and documented follow-up of 31 patients with an echocardiographic finding of a clinically silent coronary artery fistula from 1986 to 1997 were analyzed. Mean age at diagnosis was 7.2+/-8.4 years. Indications for echocardiography were murmur (n = 23), congenital heart disease (n = 2), cardiomegaly (n = 2), chest pain (n = 1), stridor (n = 1), syncope (n = 1), and chest trauma (n = 1). CAF were detected with color Doppler flow mapping in all patients. The origin of the fistula was from the left coronary artery system (n = 27), right coronary artery system (n = 3), and bilateral (n = 1). The exit sites were the pulmonary artery (n = 18), right ventricle (n = 8), right atrium (n = 2), and left ventricle (n = 3). Global and regional left ventricular function were normal in all patients at presentation and follow-up. Spontaneous closure of the fistula was documented in 7 patients (23%) at mean follow-up of 2.6+/-2.0 years. In 23 patients the fistula persisted without intervention. All patients remained asymptomatic, without adverse clinical events or evidence of ischemia at a mean age at follow-up of 9.3+/-9.1 years (range 4 months to 42.0). Based on this experience, there is no evidence that clinically silent CAF diagnosed incidentally by color Doppler echocardiography are associated with adverse clinical outcome in childhood and adolescence. Conservative management with continued follow-up of these patients appears to be appropriate.

Adolescent↗
PubMed1999

Evolution of risk factors influencing early mortality of the arterial switch operation.

OBJECTIVES: The present study was undertaken to determine the independent risk factors for early mortality in the current era after arterial switch operation (ASO). BACKGROUND: Prior reports on factors affecting outcome of the ASO demonstrated that abnormal coronary arterial patterns were associated with increased risk of early mortality. As diagnostic, surgical and perioperative management techniques continue to evolve, the risk factors for the ASO may have changed. METHODS: All patients who underwent the ASO at Children's Hospital, Boston between January 1, 1992 and December 31, 1996 were included. Hospital charts, echocardiographic and cardiac catheterization data and operative reports of all patients were reviewed. Demographics and preoperative, intraoperative and postoperative variables were recorded. RESULTS: Of the 223 patients included in the study (median age at ASO = 6 days and median weight = 3.5 kg), 26 patients had aortic arch obstruction or interruption, 12 had Taussig-Bing anomaly, 12 had multiple ventricular septal defects, 8 had right ventricular hypoplasia and 6 were premature. There were 16 early deaths (7%), with 3 deaths in the 109 patients considered "low risk" (2.7%). Coronary artery pattern was not associated with an increased risk of death. Compared with usual coronary anatomy pattern, however, inverted coronary patterns and single right coronary patterns were associated with increased incidence of delayed sternal closure (p = 0.003) and longer duration of mechanical ventilation (p = 0.008). In a multivariate logistic regression model using only preoperative variables, aortic arch repair at a separate procedure before ASO and smaller birth weight were independent predictors of early mortality. In a second model that included both pre- and intraoperative variables, circulatory arrest time and right ventricular hypoplasia were independent predictors of early death. CONCLUSIONS: The ASO can be performed in the current era without excess early mortality related to uncommon coronary artery patterns. Aortic arch repair before ASO, right ventricular hypoplasia, lower birth weight and longer intraoperative support continue to be independent risk factors for early mortality after the ASO.

Abnormalities, Multiple↗
PubMed1999

The thyroid hormone receptor-beta gene mutation R383H is associated with isolated central resistance to thyroid hormone.

Resistance to thyroid hormone (RTH) action is due to mutations in the beta-isoform of the thyroid hormone receptor (TR-beta). RTH patients display inappropriate central secretion of TRH from the hypothalamus and of TSH from the anterior pituitary despite elevated levels of thyroid hormone (T4 and T3). RTH mutations cluster in three hot spots in the C-terminal portion of the TR-beta. Most individuals with TR-beta mutations have generalized resistance to thyroid hormone, where most tissues in the body are hyporesponsive to thyroid hormone. The affected individuals are clinically euthyroid or even hypothyroid depending on the severity of the mutation. Whether TR-beta mutations cause a selective form of RTH that only leads to central thyroid hormone resistance is debated. Here, we describe an individual with striking peripheral sensitivity to graded T3 administration. The subject was enrolled in a protocol in which she received three escalating T3 doses over a 13-day period. Indexes of central and peripheral thyroid hormone action were measured at baseline and at each T3 dose. Although the patient's resting pulse rose only 11% in response to T3, her serum ferritin, alanine aminotransferase, aspartate transaminase, and lactate dehydrogenase rose 320%, 117%, 121%, and 30%, respectively. In addition, her serum cholesterol, creatinine phosphokinase, and deep tendon reflex relaxation time fell (25%, 36%, and 36%, respectively). Centrally, the patient was sufficiently resistant to T3 that her serum TSH was not suppressed with 200 microg T3, orally, daily for 4 days. The patient's C-terminal TR exons were sequenced revealing the mutation R383H in a region not otherwise known to harbor TR-beta mutations. Our clinical evaluation presented here represents the most thorough documentation to date of the central thyroid hormone resistance phenotype in an individual with an identified TR-beta mutation.

Body Weight↗
PubMed1999

Cardiac complications in children with human immunodeficiency virus infection. Pediatric Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection (P2C2 HIV) Study Group, National Heart, Lung, and Blood Institute.

OBJECTIVE: Although numerous cardiac abnormalities have been reported in HIV-infected children, precise estimates of the incidence of cardiac disease in these children are not well-known. The objective of this report is to describe the 2-year cumulative incidence of cardiac abnormalities in HIV-infected children. METHODOLOGY DESIGN: Prospective cohort (Group I) and inception cohort (Group II) study design. SETTING: A volunteer sample from 10 university and public hospitals. PARTICIPANTS: Group I consisted of 205 HIV vertically infected children enrolled at a median age of 22 months. This group was comprised of infants and children already known to be HIV-infected at the time of enrollment in the study. Most of the children were African-American or Hispanic and 89% had symptomatic HIV infection at enrollment. The second group included 611 neonates born to HIV-infected mothers, enrolled during fetal life or before 28 days of age (Group II). In contrast to the older Group I children, all the Group II children were enrolled before their HIV status was ascertained. INTERVENTIONS: According to the study protocol, children underwent a series of cardiac evaluations including two-dimensional echocardiogram and Doppler studies of cardiac function every 4 to 6 months. They also had a 12- or 15-lead surface electrocardiogram (ECG), 24-hour ambulatory ECG monitoring, and a chest radiograph every 12 months. OUTCOME MEASURES: Main outcome measures were the cumulative incidence of an initial episode of left ventricular (LV) dysfunction, cardiac enlargement, and congestive heart failure (CHF). Because cardiac abnormalities tended to cluster in the same patients, we also determined the number of children who had cardiac impairment which we defined as having either left ventricular fractional shortening (LV FS) </=25% after 6 months of age, CHF, or treatment with cardiac medications. RESULTS: CARDIAC ABNORMALITIES: In Group I children (older cohort), the prevalence of decreased LV function (FS </=25%) was 5.7% and the 2-year cumulative incidence (excluding prevalent cases) was 15.3%. The prevalence of echocardiographic LV enlargement (LV end-diastolic dimension z score >2) at the time of the first echocardiogram was 8. 3%. The cumulative incidence of LV end-diastolic enlargement was 11. 7% after 2 years. The cumulative incidence of CHF and/or the use of cardiac medications was 10.0% in Group I children. There were 14 prevalent cases of cardiac impairment (LV FS </=25% after 6 months of age, CHF, or treatment with cardiac medications) in Group I. After excluding these prevalent cases, the 2-year cumulative incidence of cardiac impairment was 19.1% among Group I children and 80.9% remained free of cardiac impairment after 2 years of follow-up. Within Group II (neonatal cohort), the 2-year cumulative incidence of decreased LV FS was 10.7% in the HIV-infected children compared with 3.1% in the HIV-uninfected children. LV dilatation was also more common in Group II infected versus uninfected children (8.7% vs 2.1%). The cumulative incidence of CHF and/or the use of cardiac medications was 8.8% in Group II infected versus 0.5% in uninfected subjects. The 1- and 2-year cumulative incidence rates of cardiac impairment for Group II infected children were 10.1% and 12.8%, respectively, with 87.2% free of cardiac impairment after the first 2 years of life. MORTALITY: In the Group I cohort, the 2-year cumulative death rate from all causes was 16.9% [95% CI: 11.7%-22. 1%]. The 1- and 2-year mortality rates after the diagnosis of CHF (Kaplan-Meier estimates) were 69% and 100%, respectively. In the Group II cohort, the 2-year cumulative death rate from all causes was 16.3% [95% CI: 8.8%-23.9%] in the HIV-infected children compared with no deaths among the 463 uninfected Group II children. Two of the 4 Group II children with CHF died during the 2-year observation period and 1 more died within 2 years of the diagnosis of CHF. The 2-year mortality rate after the

Adolescent↗
PubMed1998

Prevalence of congenital cardiovascular malformations in children of human immunodeficiency virus-infected women: the prospective P2C2 HIV Multicenter Study. P2C2 HIV Study Group, National Heart, Lung, and Blood Institute, Bethesda, Maryland.

OBJECTIVES: The purpose of the study was to assess the effects of maternal HIV-1 (human immunodeficiency virus) infection and vertically transmitted HIV-1 infection on the prevalence of congenital cardiovascular malformations in children. BACKGROUND: In the United States, an estimated 7000 children are born to HIV-infected women annually. Previous limited reports have suggested an increase in the prevalence of congenital cardiovascular malformations in vertically transmitted HIV-infected children. METHODS: In a prospective longitudinal multicenter study, diagnostic echocardiograms were performed at 4-6-month intervals on two cohorts of children exposed to maternal HIV-1 infection: 1) a Neonatal Cohort of 90 HIV-infected, 449 HIV-uninfected and 19 HIV-indeterminate children; and 2) an Older HIV-Infected Cohort of 201 children with vertically transmitted HIV-1 infection recruited after 28 days of age. RESULTS: In the Neonatal Cohort, 36 lesions were seen in 36 patients, yielding an overall congenital cardiovascular malformation prevalence of 6.5% (36/558), with a 8.9% (8/90) prevalence in HIV-infected children and a 5.6% (25/449) prevalence in HIV-uninfected children. Two children (2/558, 0.4%) had cyanotic lesions. In the Older HIV-Infected Cohort, there was a congenital cardiovascular malformation prevalence of 7.5% (15/201). The distribution of lesions did not differ significantly between the groups. CONCLUSIONS: There was no statistically significant difference in congenital cardiovascular malformation prevalence in HIV-infected versus HIV-uninfected children born to HIV-infected women. With the use of early screening echocardiography, rates of congenital cardiovascular malformations in both the HIV-infected and HIV-uninfected children were five- to ten-fold higher than rates reported in population-based epidemiologic studies but not higher than in normal populations similarly screened. Potentially important subclinical congenital cardiovascular malformations were detected.

Cohort Studies↗
PubMed1998

Evaluation of regional differences in right ventricular systolic function by acoustic quantification echocardiography and cine magnetic resonance imaging.

BACKGROUND: Accurate quantitative evaluation of right ventricular (RV) function has been limited by its complex structural geometry. Although embryological and anatomic observations suggest that the RV is composed of 2 distinct components, the RV sinus and infundibulum, most studies on RV dimensions and function viewed it as a single chamber. This study was designed to determine the volumes, relative contribution to global systolic function, and temporal course of contraction and relaxation of the RV sinus and infundibulum. METHODS AND RESULTS: Thirty-one individuals without heart disease (aged 1 month to 17 years, 16 boys and 15 girls) participated in this study. Instantaneous area over time, its derivatives, and the temporal course of contraction and relaxation were studied by acoustic quantification echocardiography and phonocardiography in 20 individuals. Global and regional RV volumes and ejection fraction were determined by cine MRI in 11 individuals. The RV sinus made up 81+/-6% of the combined RV end-diastolic volume and 87+/-4% of the combined stroke volume. The infundibulum accounted for the remaining 19+/-6% and 13+/-4%, respectively (P<0.0001). Compared with the infundibulum, the extent of RV sinus fiber shortening was significantly greater: for ejection fraction (56+/-11% versus 38+/-13%, P<0.001), fractional area change (42+/-14% versus 28+/-9%, P<0.0001), and dA/dt (27+/-17% versus 13+/-6%, P<0.0001). Analysis of temporal course of contraction and relaxation (expressed as percentage of the cardiac cycle to adjust for differences in heart rate) showed that the infundibulum follows the RV sinus: onset of contraction 53%+/-14 versus 19+/-11% of systole, time to peak systole 115+/-16% versus 97+/-19% (P< or =0.01), indicating a peristalsis-like pattern of contraction and relaxation. CONCLUSIONS: The results of this study demonstrate significant regional differences between the sinus and infundibulum components of the RV with regard to contribution to stroke volume, extent of fiber shortening, and sequence of mechanical activation. These data from normal individuals can be used in future research on RV function in pathological conditions.

Adolescent↗
PubMed1998

Left ventricular structure and function in children infected with human immunodeficiency virus: the prospective P2C2 HIV Multicenter Study. Pediatric Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection (P2C2 HIV) Study Group.

BACKGROUND: The frequency of, course of, and factors associated with cardiovascular abnormalities in pediatric HIV are incompletely understood. METHODS AND RESULTS: A baseline echocardiogram (median age, 2.1 years) and 2 years of follow-up every 4 months were obtained as part of a prospective study on 196 vertically HIV-infected children. Age- or body surface area-adjusted z scores were calculated by use of data from normal control subjects. Although 88% had symptomatic HIV infection, only 2 had CHF at enrollment, with a 2-year cumulative incidence of 4.7% (95% CI, 1.5% to 7.9%). All mean cardiac measurements were abnormal at baseline (decreased left ventricular fractional shortening [LV FS] and contractility and increased heart rate and LV dimension, mass, and wall stresses). Most of the abnormal baseline cardiac measurements correlated with depressed CD4 cell count z scores and the presence of HIV encephalopathy. Heart rate and LV mass showed significantly progressive abnormalities, whereas FS and contractility tended to decline. No association was seen between longitudinal changes in FS and CD4 cell count z score. Children who developed encephalopathy during follow-up had depressed initial FS, and FS continued to decline during follow-up. CONCLUSIONS: Subclinical cardiac abnormalities in HIV-infected children are common, persistent, and often progressive. Dilated cardiomyopathy (depressed contractility and dilatation) and inappropriate LV hypertrophy (elevated LV mass in the setting of decreased height and weight) were noted. Depressed LV function correlated with immune dysfunction at baseline but not longitudinally, suggesting that the CD4 cell count may not be a useful surrogate marker of HIV-associated LV dysfunction. However, the development of encephalopathy may signal a decline in FS.

AIDS Dementia Complex↗
PubMed1998

Development and validation of an echocardiographic model for predicting progression of discrete subaortic stenosis in children.

The clinical course of discrete subaortic stenosis (DSS) varies considerably between patients. This study was performed to identify echocardiographic characteristics of DSS that distinguish progressive from nonprogressive disease. The study included 100 patients from 2 institutions and was performed in 2 stages. In phase I, a prediction model was developed based on multivariate analysis of morphometric and Doppler variables obtained from the initial echocardiogram in 52 children with DSS from Texas Children's Hospital. In phase II, the performance characteristics of the prediction model were tested in 48 patients with DSS followed at Children's Hospital in Boston. Patients were divided into 3 outcome groups: nonprogressive, progressive, and intermediate progression. In phase I, multivariate analysis identified 3 independent predictors of progressive disease: indexed aortic valve to subaortic membrane distance, anterior mitral leaflet involvement, and initial Doppler gradient. The logistic regression equation--Probability = [1 + e-(-322+0.334X1+4.06X2-0.708X3)](-1), where X = initial gradient in mm Hg; X2 = absence (0) or presence (1) of mitral leaflet involvement; and X3 = indexed distance between aortic valve and subaortic membrane in mm/body surface area0.5 were used to predict progression. When the prediction model was applied to phase II study patients, none of the patients with nonprogressive DSS had a prediction value > 0.29 and none of the patients with progressive DSS had a prediction value < 0.58. Thus, a prediction value > 0.55 yielded a 100% sensitivity and 100% specificity for distinguishing progressive from nonprogressive DSS. Patients with intermediate progression were indistinguishable from progressive DSS but were clearly separable from nonprogressing patients. We conclude that progressive subaortic obstruction in children with DSS can be predicted from morphologic, morphometric, and Doppler echocardiographic analysis of left ventricular outflow.

Aortic Valve Stenosis↗
PubMed1998

Accuracy of echocardiography for detection of aortic arch obstruction after stage I Norwood procedure.

BACKGROUND: Echocardiography has been widely used in postoperative assessment after stage I Norwood procedure, but its accuracy in detecting aortic arch obstruction (AAO) has not been determined. This study was designed to determine the accuracy of echocardiography in the diagnosis of AAO after stage I Norwood procedure, identify echocardiographic predictors of arch obstruction, and examine the time course of its development. METHODS: The records and echocardiography reports of 139 patients who survived stage I Norwood procedure were reviewed. Reference standard for the diagnosis of AAO was catheterization, surgery, or autopsy. RESULTS: AAO was diagnosed by reference standard criteria in 31 (22%) patients. Echocardiography correctly diagnosed AAO in 19 patients, missed the diagnosis in five, and wrongly predicted AAO in eight, yielding a 73% sensitivity, 92% specificity, 70% positive predictive value, and 88% accuracy. Moderate or severe right ventricular dysfunction, moderate or severe tricuspid regurgitation, and an abnormal abdominal aortic Doppler flow pattern were more common in patients with AAO. The probability of AAO developing within 6 months after stage I Norwood procedure was 21.1%, with a very small likelihood after that point. Beyond the first 30 days after surgery, the risk of death was higher in patients in whom AAO developed compared with those in whom it did not (relative risk 5.9, 95% confidence interval 2.7 to 13.2). CONCLUSIONS: Echocardiography is a highly specific modality in detecting AAO after stage I Norwood procedure but its sensitivity is limited. Because of the increased risk of death associated with AAO and because most obstructions develop between 1 and 6 months postoperatively, early cardiac catheterization with possible intervention should be considered in patients with moderate or severe right ventricular dysfunction, moderate or sever tricuspid regurgitation, or an abnormal abdominal Doppler flow pattern during that period.

Aortic Arch Syndromes↗
PubMed1998

Coronary artery dimensions may be misclassified as normal in Kawasaki disease.

BACKGROUND: Current American Heart Association guidelines indicate that patients with Kawasaki disease and no coronary artery abnormalities on echocardiography at any stage of illness may be discharged from cardiologic follow-up 1 year after onset of illness. METHODS AND RESULTS: To determine whether coronary artery dimensions in patients with Kawasaki disease whose vessels are classified as "normal" by Japanese Ministry of Health criteria have a distribution similar to expected population norms when adjusting for body surface area, we studied 125 patients during 4 intervals from onset of illness: (1) 10 days or less, (2) 2 weeks (11 to 21 days), (3) 6 weeks (22 days to 3 months), and (4) 1 year (4 months to 1.5 years). Using two-dimensional echocardiography, we measured the internal lumen diameter of the left main, proximal left anterior descending, and proximal right coronary arteries. Mean body surface area-adjusted dimensions of the proximal left anterior descending and right coronary arteries were significantly larger (P < .01) in patients with Kawasaki disease than those in subjects in all periods, except for a marginal difference at 6 weeks for the proximal right coronary artery (P = .02); for the left main coronary artery, this difference achieved statistical significance in the period of 10 days or less, with a trend at 2 weeks (P = .02). Among patients classified as having normal coronary arteries on all echocardiograms by the Japanese Ministry of Health criteria, 27% had at least 1 body surface area-adjusted coronary dimension more than 2 standard deviations above the expected mean. CONCLUSIONS: Coronary artery dilation in Kawasaki disease is thus more prevalent than previously reported, highlighting the need for systematic long-term surveillance of this population.

Adolescent↗
PubMed1998

Verapamil therapy in infants with hypertrophic cardiomyopathy.

We sought to evaluate the safety and efficacy of acute and chronic treatment with verapamil in infants with hypertrophic cardiomyopathy. Prior studies have shown an improvement in adults with hypertrophic cardiomyopathy who were treated with verapamil. Acutely, it reduced the degree of left ventricular outflow tract obstruction. Chronic therapy was associated with an improvement in symptoms and increased long-term survival. To date, no data are available on the efficacy of this drug in infants with hypertrophic cardiomyopathy. We evaluated prospectively the safety and efficacy of verapamil in infants. The acute and chronic effects of verapamil on infants with an echocardiographic diagnosis of hypertrophic cardiomyopathy were evaluated at a single institution between 1980 and 1994, with long-term follow-up available until 1996. Acute effects of an intravenous bolus of 0.1 mg/kg and infusion at 0.007 mg/kg/min were evaluated, where possible, in the cardiac catheterization laboratory. Oral verapamil at 3-5 mg/kg/day was started after catheterization. Follow-up included serial clinical, echocardiographic and Holter monitoring. A total of 22 patients were studied, 17 having a presumed diagnosis of primary hypertrophic cardiomyopathy including three with Noonan's syndrome. Acute infusion of the drug was well tolerated by all, without adverse electrophysiological effects. Haemodynamic effects were consistent with a negative inotropic action with significant falls in cardiac index (4.6+/-1.2 to 4.1+/-0.9 l/min/m2), systolic blood pressure (88+/-16 to 82+/-14 mmHg) and gradient across the left ventricular outflow tract (nine patients 48.2+/-30.4 to 28.4+/-24.1 mmHg). End-diastolic pressure was unchanged (14.0+/-6.8 to 13.9+/-4.7 mmHg). Three patients with primary hypertrophic cardiomyopathy died (two while being treated). In the group with primary hypertrophic cardiomyopathy continuing with long-term treatment, follow-up revealed regression in two, progression in three (two died) and stability in 10. For those treated, there was a trend towards improvement in clinical status. Verapamil is well tolerated acutely in infants with hypertrophic cardiomyopathy. The outcome was considerably better in these patients compared with prior reports, though careful long-term assessment is needed.

Administration, Oral↗
PubMed1998

Relationship between cumulative anthracycline dose and late cardiotoxicity in childhood acute lymphoblastic leukemia.

PURPOSE: Late anthrocycline cardiotoxicity after treatment for childhood cancer is common and often progressive. A safe anthracycline dose that will not result in late cardiac abnormalities has not been established due to the limited dose ranges used in existing studies. PATIENTS AND METHODS: To determine the relationship between cumulative anthracycline dose and late cardiotoxicity, we performed echocardiograms on 189 survivors of childhood acute lymphoblastic leukemia a median of 8.1 years (range, 2.0 to 23.4) after completion of anthracycline therapy. Patients were treated according to protocols that used widely varying cumulative anthracycline doses, but comparable nonanthracycline chemotherapy. Patients were divided into four groups based on the city of treatment and cumulative anthracycline dose: Copenhagen, 0 to 23 mg/m2 (n = 32); Boston, 45 mg/m2 (n = 17); Copenhagen, 73 to 301 mg/m2 (n = 53); and Boston, 244 to 550 mg/m2 (n = 87). Left ventricular dimension and fractional shortening were adjusted for sex and age or body-surface area through use of a control population (n = 296), and then compared among the four groups. RESULTS: Mean left ventricular dimension was significantly increased in the high-dose Boston group (observed:predicted value, 4.57 cm:4.45 cm; P = .002) and significantly higher than in the two Copenhagen groups. In the three lower-dose groups, there was no significant increase in mean left ventricular dimension, and the groups were not significantly different from each other. Similarly, the mean left ventricular fractional shortening was significantly depressed in the high-dose Boston group (observed:predicted value, 29.0%:33.8%; P = .0001) and significantly lower than in the three lower-dose groups. CONCLUSION: Depressed left ventricular fractional shortening and left ventricular dilatation were uncommon years after treatment of childhood leukemia when cumulative anthracycline doses were < or = 300 mg/m2.

Adolescent↗
PubMed1997

Left ventricular mechanics and geometry in patients with congenital complete atrioventricular block.

BACKGROUND: Radiographic evidence of cardiomegaly is common in patients with congenital complete atrioventricular block (CCAVB). It has been speculated that left ventricular (LV) remodeling and increased stroke volume counteract the bradycardia, but the effects of slow heart rate and atrioventricular asynchrony on LV dimensions, geometry, wall stress, and function have not been examined in detail. METHODS AND RESULTS: Thirty patients with CCAVB without associated congenital heart disease (mean age, 8.5+/-5.3 years; range, 0.2 to 20 years) were included in a cross-sectional two-institution study. Thirty-five echocardiograms were performed using standard techniques. ECG and 24-hour ECG recordings were reviewed. Seven patients did not receive a pacemaker, whereas 23 patients underwent pacemaker implantation after the echocardiogram. Compared with normal control subjects, LV volume (Z score=1.5+/-1.3) and LV mass (Z=1.2+/-1.5) were significantly increased, whereas LV mass-to-volume ratio (1.1+/-0.3) and geometry (short-axis diameter/length ratio=0.65+/-0.09) were normal. LV end-systolic stress (ESS) (a measure of afterload) was normal (Z score=0.2+/-2.3), whereas shortening fraction (Z=3+/-2.9) and velocity of circumferential fiber shortening (VCF) (Z=3+/-3.1) were increased. The relationship between VCF and ESS (a preload-insensitive and afterload-adjusted index of contractility) was increased (Z=2.2+/-2) with only small increase in preload (Z=1.02+/-1.1). Regression analyses showed no significant change over age in LV mass, volume, geometry, loading conditions, or systolic function. Patients who ultimately met criteria for pacemaker implantation did not differ from those who did not in terms of heart rate or LV function but did have increased LV volume (Z score=1.8+/-1.4 versus 0.4+/-0.9, P=.03) and LV mass (Z score=1.7+/-1.2 versus 0.2+/-1.7, P=.001) compared to the unpaced group. CONCLUSIONS: In most patients with CCAVB, the LV was enlarged with normal geometry and enhanced systolic function during the first two decades of life. The degree of LV dilation and enhanced function did not significantly change with age. In patients who ultimately underwent pacemaker implantation LV function did not differ from those who remained unpaced, but evidence of a slightly increased load manifested as increased end-diastolic volume and mass.

Adolescent↗
PubMed1997

Functional outcome after the Fontan operation: factors influencing late morbidity.

OBJECTIVES: The purpose of this study was to describe the functional outcome of a large number of patients after modifications of the Fontan operation and to investigate perioperative risk factors that might influence late functional state. METHODS: A comprehensive cross-sectional review of the first 500 patients undergoing a Fontan operation at our institution was undertaken. Those surviving with an intact Fontan circulation were reviewed by questionnaire to assess functional status and medication history. Medical records, chest roentgenograms, echocardiograms, cardiac catheterizations, and laboratory investigations were also reviewed to assess postoperative status. RESULTS: Three hundred sixty-three long-term survivors with an intact Fontan circulation were identified during cross-sectional follow-up. Median age at operation was 5.0 years (range 0.4 to 31 years), and median follow-up was 5.4 years (range 1.7 to 20 years). Most patients (91.1%) were in New York Heart Association class I or II. In a multivariate model, poor (class III or IV) functional state was associated with longer duration of follow-up (p < 0.001), a prior atrial septectomy (p = 0.03), and a prior main pulmonary artery-ascending aorta anastomosis (p = 0.05). CONCLUSIONS: A poor functional outcome is uncommon after the Fontan operation but becomes more frequent with increasing duration of follow-up.

Adolescent↗