Safety and efficacy of carvedilol therapy for patients with dilated cardiomyopathy secondary to muscular dystrophy.

BACKGROUND: By the age of 20 years, almost all patients with Duchenne's or Becker's muscular dystrophy have experienced dilated cardiomyopathy (DCM), a condition that contributes significantly to their morbidity and mortality. Although studies have shown carvedilol to be an effective therapy for patients with other forms of DCM, few data exist concerning its safety and efficacy for patients with muscular dystrophy. This study aimed to evaluate the safety and efficacy of carvedilol for patients with DCM. METHODS: A clinical trial at an outpatient clinic investigated 22 muscular dystrophy patients, ages 14 to 46 years, with DCM and left ventricular ejection fraction (LVEF) less than 50%. Carvedilol up-titrated over 8 weeks then was administered at the maximum or highest tolerated dose for 6 months. Baseline and posttreatment cardiac magnetic resonance imaging (CMR), echocardiography, and Holter monitoring were recorded. RESULTS: Carvedilol therapy was associated with a modest but statistically significant improvement in CMR-derived ejection fraction (41% +/- 8.3% to 43% +/- 8%; p < 0.02). Carvedilol also was associated with significant improvements in both the mean rate of pressure rise (dP/dt) during isovolumetric contraction (804 +/- 216 to 951 +/- 282 mmHg/s; p < 0.05) and the myocardial performance index (0.55 +/- 0.18 to 0.42 +/- 0.15; p < 0.01). A trend toward improved shortening fraction, E/E' ratio, and isovolumetric relaxation time also was observed. Two patients had runs of nonsustained ventricular tachycardia exceeding 140 beats per minute (bpm) before carvedilol administration. Ventricular tachycardia exceeding 140 bpm was not observed after carvedilol therapy. Carvedilol was well tolerated, and no serious adverse events were identified. CONCLUSIONS: Carvedilol therapy appears to be safe for patients with DCM secondary to muscular dystrophy and produces a modest improvement in systolic and diastolic function.

Prospective single-arm protocol of carvedilol in children with ventricular dysfunction.

The objective of this study was to evaluate the safety and efficacy of carvedilol in pediatric patients with stable moderate heart failure. We performed a single-arm prospective drug trial at three academic medical centers and the results were compared to historical controls. Patients were 3 months to 17 years old with an ejection fraction <40% in the systemic ventricle for at least 3 months on maximal medical therapy including ACE inhibitors. Treated patients were started on 0.1 mg/kg/day and uptitrated to 0.8 mg/kg/day or the maximal tolerated dose. Echocardiographic parameters of function were prospectively measured at entry and at 6 months. Two composite endpoints were recorded: severe decline in status and significant clinical change. Adverse events were reviewed by a safety committee. Data were also collected from untreated controls with dilated cardiomyopathy meeting entry criteria, assessed over a similar time frame. Twenty patients [12 dilated cardiomyopathy (DCM) and 8 congenital] with a median age of 8.4 years (range, 8 months to 17.8 years) were treated with carvedilol. Three patients discontinued the drug during the study. At entry, there was no statistical difference in age, weight, or ejection fraction between the treated group and controls. The ejection fraction of the treated DCM group improved significantly from entry to 6 months (median, 31 to 40%, p = 0.04), with no significant change in ejection fraction in the control group [median, 29 to 27%, p = not significant (NS)]. The median increase in ejection fraction was larger for the treated DCM group than for the untreated DCM controls (7 vs 0%, p = 0.05). By Kaplan-Meier analysis, time to death or transplant tended to be longer in treated patients (p = 0.07). The difference in the proportion of patients with severe decline in status or significant clinical change in the treated group was not significant compared to the controls (5 vs 12%, p = NS). We conclude that in this prospective protocol of pediatric patients, the use of adjunct carvedilol in the DCM group improved ejection fraction compared to untreated controls and trended toward delaying time to transplant or death.

Racial and ethnic disparities in mortality following congenital heart surgery.

Our objective was to assess risk-adjusted racial and ethnic disparities in mortality following congenital heart surgery. We studied 8483 congenital heart surgical cases from the Kids' Inpatient Database 2000. Black sub-analysis was performed using predetermined regional categories. For our Hispanic sub-analyses, we categorized Hispanics into state groups according to a state's predominant Hispanic group: West (Mexican-American), Southeast (Cuban-American), Northeast (Puerto Rican), and Mixed/Heterogeneous. Risk adjustment was performed using the Risk Adjustment for Congenital Heart Surgery method. Multivariate analyses assessed the effect of race/ethnicity and Hispanic state group on mortality and explored the effects of gender, income, insurance type, and region. Black children had a higher risk for death than Whites odds ratio (OR), [1.65; p = 0.003]. Hispanics and the Cuban-American state group showed a trend toward a higher death risk (Hispanic: OR, 1.24; p = 0.16; Southeast Cuban-American: OR 1.55; p = 0.08). Disparities were not influenced by insurance. Among Blacks, disparities were greatest in the Northeast region (OR, 2.25; p = 0.007). After adjusting for gender, income, and region, Blacks (OR, 1.76; p = 0.002) and Hispanics (OR, 1.34; p = 0.05) had a higher death risk. Racial and ethnic disparities in risk-adjusted mortality following congenital heart disease exist for Blacks and Hispanics. These disparities are not due to insurance but are partially explained by gender and region.

The RACHS-1 risk categories reflect mortality and length of hospital stay in a large German pediatric cardiac surgery population.

OBJECTIVES: The Risk Adjusted classification for Congenital Heart Surgery (RACHS-1) was published in January 2002, based on 4370 operations registered by the Pediatric Cardiac Care Consortium. It is designed for being easily applicable also for retrospective analysis of hospital discharge data sets; the classification was not developed for patients with heart transplantations, ventricular assist devices or patients above 18 years. We apply this classification to our 2368 correspondent procedures that were performed consecutively on 2223 patients between June 1996 and October 2002 in Bad Oeynhausen and analyze its relation to mortality and length of hospital stay. METHODS: The procedures were grouped by the 6 RACHS-1 categories. Groping criteria were mainly the performed procedures; for few procedures age or diagnoses are needed in addition. The classification process itself took less than 10 working hours. Risk group frequencies in our/ the PCCC population were 1: 368/964 (15.5%/22.0%), 2: 831/1433 (35.1%/33.1%), 3: 744/1523 (31.4%/34.7%), 4: 284/276 (12.0%/6.3%), 5: 4/4 (0.2%/0.1%), 6: 137/168 (5.3%/3.8%). 18.8%/19.2% were under 1 month, 37.5%/31.6% 1-12 months of age, respectively. RESULTS: Hospital mortality (%) in our population/ the PCCC Group 1-6 was: 0.3/0.4, 4.0/3.8, 5.6/8.5, 9.9/19.4, 50.0/0, 40.1/47.7%. Geometric means of total (13.1, 19.6, 23.5, 29.1, 31.5, 52.6 days, respectively) and postoperative length of stay of survivors show significant differences between the single risk groups. The prediction capacity of the score as expressed by the area under the receiver-operator curve was nearly equal to the value found for the American hospital discharge data sets. Length of stay rises exponentially with the RACHS-1 category. However, the RACHS-1 category explains only 13.5% of the total and 16.8% of individual postoperative lengths of hospital stay in survivors. CONCLUSION: The RACHS-1 classification is applicable to European pediatric populations, too. Category Distribution, outcome class distinction capacity, distribution and mortality are similar. RACHS-1 is able to classify patients into significantly different groups concerning total and postoperative hospital stay duration, although there remains a large variability within the groups.

Morbidities in patients with hypoplastic left heart syndrome.

We sought to document morbidities and growth for patients with hypoplastic left heart syndrome (HLHS) to inform the initial surgical decision and understand healthcare needs. Data were obtained on 137 patients with HLHS, born between 1989 and 1994, who survived staged surgery ( n = 62) or transplantation ( n = 75) and had follow-up information available from four pediatric cardiac surgical centers. In patients with HLHS older than 1 year of age at follow-up, 93% experienced at least one major postsurgical morbidity. Morbidities depended on the surgery received. Hypertension, renal compromise, and abnormal infections were more common in transplanted patients than staged surgery patients. Staged surgery patients used more anticongestive medications and experienced more morbidities requiring interventional catheterization than did transplanted patients. Rejection was common for transplanted patients. On average these children spent 23 days per year in the hospital. Patients with HLHS were small for their age; 43% of staged surgery patients weighed below the third percentile at last information, compared to 19% of transplanted patients ( p = 0.003). The median height percentile was the 10th in both groups. Normal activity level was reported in more transplanted patients (90%) than staged surgery patients (49%; p < 0.001). Trade-offs between mortality and morbidity outcomes can help inform the initial surgical decision.

Health-related quality of life in children attending a cardiology clinic.

Our purpose was to evaluate the impact of suspicion or confirmation of heart disease on the physical and psychosocial health of children. We utilized the Child Health Questionnaire (CHQ PF-50). Children ages 5 to 18 years attending a general cardiology clinic were eligible. Those with primary noncardiac diagnoses unrelated to heart disease were excluded. Children with similar conditions were grouped together for analysis. Group and subgroup means were compared to a U.S. population normative sample using the two-sample t test. The CHQ was administered to 321 patients (median age, 10.6 years). Overall, parents reported mean Physical and Psychosocial Summary Scores comparable to those for the normative sample (mean, 51.5 vs 53.0, p = 0.04; mean, 52.3 vs 51.2, p = 0.10). There was a trend toward worse physical health in most subgroups, especially those with cardiomyopathy (CM) (46.5; p = 0.01), and a comparable trend toward better psychosocial health except in those requiring major interventions. In subscale analyses, most subgroups reported worse Physical Functioning than the normative sample, especially CM (85.1 vs 96.1; p = 0.02). Parents of children with CM (53.2 vs 73.0; p = 0.002) and the intervention subgroups (except minor) reported worse General Health Perceptions. Parents experienced increased Parental Impact-Emotional, especially parents of children undergoing evaluations for chest pain (62.5 vs 80.3; p = 0.007). Most parents reported comparable or better health for the Family Cohesion and Bodily Pain subscales. Generally, parents of children attending a cardiology clinic report physical and psychosocial health comparable to that for the general U.S. population. However, diagnosis or confirmation of heart disease resulted in worse physical functioning and health perceptions and a significant negative emotional impact on parents.

Regional racial and ethnic differences in mortality for congenital heart surgery in children may reflect unequal access to care.

The objective of this study was to explore racial differences in mortality for congenital heart surgery. We performed a population-based retrospective cohort study using hospital discharge abstract data from four states in 1996. The outcome measure was risk-adjusted in-hospital mortality. Cases of pediatric congenital heart surgery were classified into six risk categories using the Risk Adjustment in Congenital Heart Surgery method. Differences in risk-adjusted in-hospital mortality among racial groups were explored. Analyses stratified by state were used to identify regional differences. Of 5791 cases, 4822 (83%) were assigned to a risk group for analysis. Surgical mortality differed for whites compared to non-whites (3.7 vs 5.1%, p = 0.02). Among non-white groups, unadjusted mortality rates varied: Asian, 5.3%; black, 4.1%; Hispanic 4.9%; other, 7.3%; and missing, 7.6% (p = 0.008). Adjusted mortality also differed by race but was inconsistent across regions, making explanatory factors based solely on biology implausible. For example, compared to whites, blacks had a higher risk of dying in Massachusetts [odds ratio (OR) = 6.39, p = 0.08] but lower in Pennsylvania (OR = 0.41, p = 0.009). Adding insurance type to models did not eliminate racial differences. In risk-adjusted analyses, non-white groups had a higher risk of dying after congenital heart surgery than whites. Inconsistent effects among regions suggest that differential mortality is due to unequal access to care rather than biology.

Risk of death for Medicaid recipients undergoing congenital heart surgery.

The objective of this study was to explore the effect of insurance type on mortality for congenital heart surgery. We performed a population-based retrospective cohort study using hospital discharge abstract data from five states in 1992 and 1996. The outcome measure was risk-adjusted in-hospital mortality. Cases of pediatric congenital heart surgery were identified and placed into six risk categories using the Risk Adjustment in Congenital Heart Surgery method. Multivariate analyses were used to determine the effect of insurance type on risk-adjusted mortality; regional effects were explored. Using standardized mortality ratios, institutions were grouped by outcome; within and between group differences were examined. Of 11,636 cases, 9656 (83%) were placed in a risk group for analysis. In 1996, children with Medicaid had a higher risk of death than those with commercial or managed care in both unadjusted (p = 0.002) and adjusted (p < 0.001) analyses. Overall mortality rates decreased between 1992 and 1996 (p = 0.001). However, improvement was not consistent among insurance groups. Differences were present within and between low, average, and high-mortality hospitals, suggesting that the adverse effect of Medicaid may be due to both differential referral and other differences in care among patients treated at similar institutions. Children with Medicaid insurance have a higher risk of dying after congenital heart surgery than those with commercial and some managed care insurance. Barriers to access go beyond differences in referral patterns.

A comparison of treatment strategies for hypoplastic left heart syndrome using decision analysis.

OBJECTIVES: We sought to identify the optimal treatment strategy for hypoplastic left heart syndrome (HLHS). BACKGROUND: Surgical treatment of HLHS involves either transplantation (Tx) or staged palliation of the native heart. Identifying the best treatment for HLHS requires integrating individual patient risk factors and center-specific data. METHODS: Decision analysis is a modeling technique used to compare six strategies: staged surgery; Tx; stage 1 surgery as an interim to Tx; and listing for transplant for one, two, or three months before performing staged surgery if a donor is unavailable. Probabilities were derived from current literature and a dataset of 231 patients with HLHS born between 1989 and 1994. The goal was to maximize first-year survival. RESULTS: If a donor is available within one month, Tx is the optimal choice, given baseline probabilities; if no donor is found by the end of one month, stage 1 surgery should be performed. When survival and organ donation probabilities were varied, staged surgery was the optimal choice for centers with organ donation rates < 10% in three months and with stage 1 mortality <20%. Waiting one month on the transplant list optimized survival when the three-month organ donation rate was > or =30%. Performing stage 1 surgery before listing, or performing stage 1 surgery after an unsuccessful two- or three-month wait for transplant, were almost never optimal choices. CONCLUSIONS: The best strategy for centers that treat patients with HLHS should be guided by local organ availability, stage 1 surgical mortality and patient risk factors.

Cytosolic targeting domains of gamma and delta calmodulin-dependent protein kinase II.

Ca(2+)/calmodulin-dependent protein kinase II (CaMK-II) isozyme variability is the result of alternative usage of variable domain sequences. Isozyme expression is cell type-specific to transduce the appropriate Ca(2+) signals. We have determined the subcellular targeting domain of delta(E) CaMK-II, an isozyme that induces neurite outgrowth, and of a structurally similar isozyme, gamma(C) CaMK-II, which does not induce neurite outgrowth. delta(E) CaMK-II co-localizes with filamentous actin in the perinuclear region and in cellular extensions. In contrast, gamma(C) CaMK-II is uniformly cytosolic. Constitutively active delta(E) CaMK-II induces F-actin-rich extensions, thereby supporting a functional role for its localization. C-terminal constructs, which lack central variable domain sequences, can oligomerize and localize like full-length delta(E) and gamma(C) CaMK-II. Central variable domains themselves are monomeric and have no targeting capability. The C-terminal 95 residues of delta CaMK-II also has no targeting capability but can efficiently oligomerize. These findings define a targeting domain for gamma and delta CaMK-IIs that is in between the central variable and association domains. This domain is responsible for the subcellular targeting differences between gamma and delta CaMK-IIs.

Healing response to the Clamshell device for closure of intracardiac defects in humans.

The healing response to intracardiac devices in humans is largely unknown. During regulatory trials using the Clamshell device in over 800 patients, attempts were made to perform histopathological evaluation of all explanted devices. We reviewed all those with complete histopathological examination (n = 12) from Fontan baffles (n = 4), ventricular septal defects (n = 2), and atrial septal defects (ASD; n = 6), explanted at 2.7 months to 3.6 years (median, 1.6 years), at autopsy (n = 1) or surgery (n = 11), performed for residual defects (n = 5), atrial masses (n = 3), or Fontan revision (n = 3). All but one were nearly (n = 3) or completely (n = 8) covered by pseudointima, composed of fibroelastic tissue, predominantly collagen, with focal foreign body reaction in contact with fabric, without acute inflammation or infection. Atrial masses of granulation tissue were present in three cases (ASD), opposite to protruding fractured arms. No associations were identified between coverage and closure status, position, arm fractures, or implant period. In conclusion, the healing response to transcatheter Clamshell implantation in humans is characterized by a relatively rapid development of a nonthrombotic pseudointima composed of fibroelastic tissue with minimal foreign body reaction. Cathet Cardiovasc Intervent 2001;54:101-111.

Heart size on chest x-ray as a predictor of cardiac enlargement by echocardiography in children.

To determine the usefulness of heart size on chest radiograph (CXR) in predicting cardiac enlargement (CE) in children, we prospectively evaluated 95 consecutive outpatients, who had both a CXR and echocardiography performed. Their median age was 5.0 years (2 days to 19.9 years). All patients underwent CXR assessment by a pediatric radiologist, with classification of cardiac silhouette as normal, borderline, or enlarged. Echocardiographic assessment of CE was performed by a pediatric echocardiographer. Sensitivity, specificity, and predictive values of the pediatric radiologist's interpretation of heart size on CXR were estimated. The presence of CE by echocardiography was used as the gold standard. Seventy-nine patients (83.2%) had no CE on CXR, and 16 patients (16.8%) had CE. Sensitivity of the CXR to identify CE was 58.8%, 95% confidence interval (CI) [32.9, 81.6], with a positive predictive value of 62.5% [35.4, 84.8]. Specificity was 92.3% [84.0, 97.1], with a negative predictive value of 91.1% [82.6, 96.4]. These data suggest that the assessment of CE on CXR to predict CE by echocardiography has a relatively high specificity and negative predictive value, but a low sensitivity and positive predictive value. The limitations of CXR as a diagnostic test should be understood by clinicians using the test when screening children for cardiac disease.

delta Ca(2+)/Calmodulin-dependent protein kinase II isozyme-specific induction of neurite outgrowth in P19 embryonal carcinoma cells.

Ca(2+)/calmodulin-dependent protein kinase II (CaMK-II) has been linked to the induction of differentiation in preneuronal cells. In these cells, delta isozymes represent the majority of CaMK-IIs expressed and are activated by differentiation stimuli. To determine whether delta CaMK-IIs are causative or coincident with in vitro differentiation, we overexpressed wild-type, constitutively active, and C-terminal domains of delta and gamma CaMK-II isozymes in mouse P19 and NIH/3T3 cells using high-efficiency transfections. At 1-2 days after transfection, only constitutively active delta CaMK-II isozymes induced branched cellular extensions in both cell types. In P19 cells, retinoic acid induced neurite extensions after 3-4 days; these extensions were coincident with a fourfold increase in endogenous CaMK-II activity. Extensions induced by both retinoic acid and delta CaMK-IIs contained class III beta-tubulin in a discontinuous or beaded pattern. C-terminal CaMK-II constructs disrupted the ability of endogenous CaMK-II to autophosphorylate and blocked retinoic acid-induced differentiation. delta CaMK-II was found along extensions, whereas gamma CaMK-II exhibited a more diffuse, cytosolic localization. These data not only support an extranuclear role for CaMK-II in promoting neurite outgrowth, but also demonstrate CaMK-II isozyme specificity in these early steps of neuronal differentiation.

Survival analysis and risk factors for mortality in transplantation and staged surgery for hypoplastic left heart syndrome.

OBJECTIVES: We compared survival in treatment strategies and determined risk factors for one-year mortality for hypoplastic left heart syndrome (HLHS) using intention-to-treat analysis. BACKGROUND: Staged revision of the native heart and transplantation as treatments for HLHS have been compared in treatment-received analyses, which can bias results. METHODS: Data on 231 infants with HLHS, born between 1989 and 1994 and intended for surgery, were collected from four pediatric cardiac surgical centers. Status at last contact for survival analysis and mortality at one year for risk factor analysis were the outcome measures. RESULTS: Survival curves showed improved survival for patients intended for transplantation over patients intended for staged surgery. One-year survival was 61% for transplantation and 42% for staged surgery (p < 0.01); five-year survival was 55% and 38%, respectively (p < 0.01). Survival curves adjusted for preoperative differences were also significantly different (p < 0.001). Waiting-list mortality accounted for 63% of first-year deaths in the transplantation group. Mortality with stage 1 surgery accounted for 86% of that strategy's first-year mortality. Birth weight <3 kg (odds ratio [OR] 2.4), highest creatinine > or =2 mg/dL (OR 4.7), restrictive atrial septal defect (OR 2.7) and, in staged surgery, atresia of one (OR 4.2) or both (OR 11.0) left-sided valves produced a higher risk for one-year mortality. CONCLUSIONS: Transplantation produced significantly higher survival at all ages up to seven years. Patients with atresia of one or both valves do poorly in staged surgery and have significantly higher survival with transplantation. This information may be useful in directing patients to the better strategy for them.

Clinical outcome of fenestrated Fontan patients after closure: the first 10 years.

BACKGROUND: The late clinical status of Fontan patients after fenestration closure is unknown. Data are now available on all patients who underwent closure from 1989 to 1999. METHODS AND RESULTS: All patients who underwent catheter closure of a Fontan fenestration were enrolled in either the Clamshell (1989 to 1994) or CardioSEAL (1996 to 1999) regulatory trials. Physiological values obtained at catheterization helped assess the hemodynamic effects of fenestration occlusion. In addition to survival, outcomes assessed included O(2) saturations, medication use, significant clinical findings (eg, heart failure, protein-losing enteropathy, or new arrhythmias), and somatic growth. Of 181 patients who underwent closure, 27 had additional significant leaks. The remaining 154 patients constituted the study group. Median time from closure to latest follow-up was 3.4 years (range 0.4 to 10.3 years). Fenestration closure increased O(2) saturation 9.4% on average (P:<0. 001). The numbers of patients receiving digoxin or diuretics decreased at the most recent follow-up compared with baseline (P:<0. 001), but use of antiarrhythmic agents increased marginally (P:=0. 05). Height and weight percentiles rose (medians of 2 and 4, respectively; P:<0.001). Clinical decompensation during follow-up of 154 patients was rare (4.5%), with 2 deaths, 3 Fontan revisions, and 1 patient each with protein-losing enteropathy and ascites. No other patient developed chronic congestive symptoms; 21 patients developed new arrhythmias, and 2 had a stroke or transient ischemic attack. CONCLUSIONS: Fenestration closure in Fontan patients was followed by improved oxygenation, reduced need for anticongestive medication, and improved somatic growth at latest follow-up. Death (1.3%) or chronic decompensation (3.2%) was rare.

Mechanism of pulmonary vein stenosis in infants with normally connected veins.

We used microscopy, immunohistochemistry, and cell culture to identify the mechanism of restenosis in 4 infants with isolated pulmonary vein stenosis. Recurrent obstruction appears to be due to myofibroblastic proliferation in this fatal disease.

Closure of patent foramen ovale for paradoxical emboli: intermediate-term risk of recurrent neurological events following transcatheter device placement.

OBJECTIVES: We report the largest and the longest follow-up to date of patients who underwent transcatheter patent foramen ovale (PFO) closure for paradoxical embolism. BACKGROUND: Closure of a PFO has been proposed as an alternative to anticoagulation in patients with presumed paradoxical emboli. METHODS: Data were collected for patients following PFO closure with the Clamshell, CardioSEAL or Buttoned Devices at two institutions. RESULTS: There were 63 patients (46 +/- 18 years) with a follow-up of 2.6 +/- 2.4 years. Fifty-four (86%) had effective closure of the foramen ovale (trivial or no residual shunt by echocardiography) while seven (11%) had mild and two (3%) had moderate residual shunting. There were four deaths (leukemia, pulmonary embolism, sepsis following a hip fracture and lung cancer). There were four recurrent embolic neurological events following device placement: one stroke and three transient events. The stroke occurred in a 56-year-old patient six months following device placement. A follow-up transesophageal echocardiogram showed a well seated device without residual shunting. Two of the four events were associated with suboptimal device performance (one patient had a significant residual shunt and a second patient had a "friction lesion" in the left atrial wall associated with a displaced fractured device arm). The risk of recurrent stroke or transient neurological event following device placement was 3.2% per year for all patients. CONCLUSION: Transcatheter closure of PFO is an alternative therapy for paradoxical emboli in selected patients. Improved device performance may reduce the risk of recurrent neurological events. Further studies are needed to identify patients most likely to benefit from this intervention.

Sudden death in patients after transcatheter device implantation for congenital heart disease.

To explore whether transcatheter intracardiac devices increase risk for sudden death, we analyzed patient and device-related variables with a case-control design. Sudden death was defined as unexpected death with abrupt onset and rapid deterioration. Cases included all patients known to have died suddenly after device closure at our institution, using 3 large databases. Controls (2:1), matched on year of procedure, were chosen randomly from the same databases. Data were obtained from medical record review. Of 777 patients who received implants between February 1989 and February 1999, 9 were known to have died suddenly (1.2%). In 27 cases and controls, diverse defects were occluded: atrial (n = 16), ventricular (n = 4), Fontan fenestration (n = 4), or other (n = 3). Cases were more likely to have had a history of serious arrhythmias (p = 0.008), severe valve regurgitation (p = 0.03), > or =1 cardiac surgery (p = 0.009), and multiple devices (p = 0.03). Cases were somewhat more likely to have pulmonary hypertension (p = 0.09), ventricular dysfunction (p = 0.09), and nonatrial septal defects (p = 0.10). Patients were less likely to have device arm fractures (p = 0.05). The following were not related to sudden death: age, weight, gender, low systemic cardiac index, end-diastolic pressure, major noncardiac disease, serious adverse events, maximum device size, malposition, and residual leak. This study suggests that sudden death was more likely to occur in device-implanted patients who had severe underlying cardiac disease and/or multiple devices. No other device-related variables were associated with sudden death.