Susan M. Fernandes

Pregnancy Outcomes in Women With Congenital Heart Disease

Background— Pregnant women with congenital heart disease are at increased risk for cardiac and neonatal complications, yet risk factors for adverse outcomes are not fully defined. Methods and Results— Between January 1998 and September 2004, 90 pregnancies at age 27.7±6.1 years were followed in 53 women with congenital heart disease. Spontaneous abortions occurred in 11 pregnancies at 10.8±3.7 weeks, and 7 underwent elective pregnancy termination. There were no maternal deaths. Primary maternal cardiac events complicated 19.4% of ongoing pregnancies, with pulmonary edema in 16.7% and sustained arrhythmias in 2.8%. Univariate risk factors included prior history of heart failure (odds ratio [OR], 15.5), NYHA functional class ≥2 (OR, 5.4), and decreased subpulmonary ventricular ejection fraction (OR, 7.7). Independent predictors were decreased subpulmonary ventricular ejection fraction and/or severe pulmonary regurgitation (OR, 9.0) and smoking history (OR, 27.2). Adverse neonatal outcomes occurred in 27.8% of ongoing pregnancies and included preterm delivery (20.8%), small for gestational age (8.3%), respiratory distress syndrome (8.3%), intraventricular hemorrhage (1.4%), intrauterine fetal demise (2.8%), and neonatal death (1.4%). A subaortic ventricular outflow tract gradient >30 mm Hg independently predicted an adverse neonatal outcome (OR, 7.5). Cardiac risk assessment was improved by including decreased subpulmonary ventricular systolic function and/or severe pulmonary regurgitation (OR, 10.3) in a previously proposed risk index developed in pregnant women with acquired and congenital heart disease. Conclusions— Maternal cardiac and neonatal complication rates are considerable in pregnant women with congenital heart disease. Patients with impaired subpulmonary ventricular systolic function and/or severe pulmonary regurgitation are at increased risk for adverse cardiac outcomes.

Implantable Cardioverter-Defibrillators in Tetralogy of Fallot

Background— Tetralogy of Fallot is the most common form of congenital heart disease in implantable cardioverter-defibrillator (ICD) recipients, yet little is known about the value of ICDs in this patient population. Methods and Results— We conducted a multicenter cohort study in high-risk patients with Tetralogy of Fallot to determine actuarial rates of ICD discharges, identify risk factors, and characterize ICD-related complications. A total of 121 patients (median age 33.3 years; 59.5% male) were enrolled from 11 sites and followed up for a median of 3.7 years. ICDs were implanted for primary prevention in 68 patients (56.2%) and for secondary prevention in 53 (43.8%), defined by clinical sustained ventricular tachyarrhythmia or resuscitated sudden death. Overall, 37 patients (30.6%) received at least 1 appropriate and effective ICD discharge, with a median ventricular tachyarrhythmia rate of 213 bpm. Annual actuarial rates of appropriate ICD shocks were 7.7% and 9.8% in primary and secondary prevention, respectively (P=0.11). A higher left ventricular end-diastolic pressure (hazard ratio 1.3 per mm Hg, P=0.004) and nonsustained ventricular tachycardia (hazard ratio 3.7, P=0.023) independently predicted appropriate ICD shocks in primary prevention. Inappropriate shocks occurred in 5.8% of patients yearly. Additionally, 36 patients (29.8%) experienced complications, of which 6 (5.0%) were acute, 25 (20.7%) were late lead-related, and 7 (5.8%) were late generator-related complications. Nine patients died during follow-up, which corresponds to an actuarial annual mortality rate of 2.2%, which did not differ between the primary and secondary prevention groups. Conclusions— Patients with tetralogy of Fallot and ICDs for primary and secondary prevention experience high rates of appropriate and effective shocks; however, inappropriate shocks and late lead-related complications are common.

Transvenous Pacing Leads and Systemic Thromboemboli in Patients With Intracardiac Shunts. A Multicenter Study

Background— The risk of systemic thromboemboli associated with transvenous leads in the presence of an intracardiac shunt is currently unknown. Methods and Results— To define this risk, we conducted a multicenter, retrospective cohort study of 202 patients with intracardiac shunts: Sixty-four had transvenous leads (group 1), 56 had epicardial leads (group 2), and 82 had right-to-left shunts but no pacemaker or implantable cardioverter defibrillator leads (group 3). Patient-years were accrued until the occurrence of systemic thromboemboli or study termination. Censoring occurred in the event of complete shunt closure, death, or loss to follow-up. Mean ages for groups 1, 2, and 3 were 33.9±18.0, 22.2±12.6, and 22.9±15.0 years, respectively. Respective oxygen saturations were 91.2±9.1%, 88.1±8.1%, and 79.7±6.7%. During respective median follow-ups of 7.3, 9.3, and 17.0 years, 24 patients had at least 1 systemic thromboembolus: 10 (15.6%), 5 (8.9%), and 9 (11.0%) in groups 1, 2, and 3, respectively. Univariate risk factors were older age (hazard ratio [HR], 1.05; P=0.0001), ongoing phlebotomy (HR, 3.1; P=0.0415), and an transvenous lead (HR, 2.4; P=0.0421). In multivariate, stepwise regression analyses, transvenous leads remained an independent predictor of systemic thromboemboli (HR, 2.6; P=0.0265). In patients with transvenous leads, independent risk factors were older age (HR, 1.05; P=0.0080), atrial fibrillation or flutter (HR, 6.7; P=0.0214), and ongoing phlebotomy (HR, 14.4; P=0.0349). Having had aspirin or warfarin prescribed was not protective. Epicardial leads were, however, associated with higher atrial (P=0.0407) and ventricular (P=0.0270) thresholds and shorter generator longevity (HR, 1.9; P=0.0176). Conclusions— Transvenous leads incur a >2-fold increased risk of systemic thromboemboli in patients with intracardiac shunts.

Cardiovascular outcomes after the arterial switch operation for D-transposition of the great arteries.

Background— Data regarding long-term outcomes after the arterial switch operation for D-transposition of the great arteries are scarce. Methods and Results— A single-institution retrospective cohort study was conducted to assess cardiovascular outcomes after an arterial switch operation between 1983 and 1999. Patients without follow-up visits within 3 years were contacted and secondary sources of information obtained. Overall, 400 patients, 154 (38.3%) with a ventricular septal defect, 238 (59.5%) with an intact septum, and 9 (2.3%) with a Taussig-Bing anomaly, were followed for a median of 18.7 years. In perioperative survivors, overall and arrhythmia-free survival rates at 25 years were 96.7±1.8% and 96.6±0.1%, respectively. Late mortality was predominantly a result of sudden deaths and myocardial infarction. At 25 years, 75.5±2.5% remained free from surgical or catheter-based reintervention. Freedom from an adverse cardiovascular event was 92.9±1.9% at 25 years. Independent predictors were a single right coronary artery (hazard ratio, 4.58; 95% confidence interval, 1.32-15.90), P=0.0166) and postoperative heart failure (hazard ratio, 6.93; 95% confidence interval, 1.57-30.62; P=0.0107). At last follow-up, the left ventricular ejection fraction was 60.3±8.9%, 97.3% had class I symptoms, and 5.2% obstructive coronary artery disease. Peak oxygen uptake was 35.1±7.6 mL/kg/min (86.1±15.1% predicted), with a chronotropic index <80% in 34.2%. At least moderate neoaortic and pulmonary regurgitation were present in 3.4% and 6.6%, respectively, and more than mild neoaortic and pulmonary stenosis in 3.2% and 10.3%. Conclusions— Long-term and arrhythmia-free survival is excellent after arterial switch operation. Although sequelae include chronotropic incompetence and neoaortic, pulmonary, and coronary artery complications, most patients maintain normal systolic function and exercise capacity.

Sudden Death and Defibrillators in Transposition of the Great Arteries With Intra-atrial Baffles A Multicenter Study

Background—Transposition of the great arteries with intra-atrial baffle repair is among the congenital heart defects at highest risk of sudden death. Little is known about mechanisms of sudden death and the role of implantable cardioverter defibrillators. Methods and Results—We conducted a multicenter cohort study in patients with transposition of the great arteries to determine actuarial rates of implantable cardioverter defibrillator shocks, identify risk factors, assess underlying arrhythmias, and characterize complications. Overall, 37 patients (age, 28.0±7.6 years; 89.2% male) were enrolled from 7 sites. Implantable cardioverter defibrillators were implanted for primary prevention in 23 (62.1%) patients and secondary prevention in 14 patients (37.8%). Annual rates of appropriate shocks were 0.5% and 6.0% in primary and secondary prevention, respectively (P=0.0366). Independent predictors were a secondary prevention indication (hazard ratio, 18.0; P=0.0341) and lack of &bgr;-blockers (hazard ratio, 16.7; P=0.0301). In patients with appropriate shocks, intracardiac electrograms documented supraventricular tachycardia preceding or coexisting with ventricular tachycardia in 50%. No patient with inducible ventricular tachycardia received an appropriate shock in comparison with 37.5% of noninducible patients (P=0.0429). Inappropriate shocks occurred in 6.6% per year, more so in patients of lesser weight (hazard ratio, 0.91 per kg; P=0.0168). Additionally, 14 patients (37.8%) experienced complications: 5 (13.5%) acute, 1 (2.7%) late generator related, and 12 (32.4%) late lead related. Conclusion—In patients with transposition of the great arteries, high rates of appropriate shocks are noted in secondary but not primary prevention. Supraventricular arrhythmias may be implicated in the etiology of ventricular tachyarrhythmias; &bgr;-blockers seem protective, and inducible ventricular tachycardia does not seem to predict future events. Inappropriate shocks and late lead-related complications are common.

Cardiovascular Outcomes Following the Arterial Switch Operation for D-Transposition of the Great Arteries

Background— Data regarding long-term outcomes after the arterial switch operation for D-transposition of the great arteries are scarce. Methods and Results— A single-institution retrospective cohort study was conducted to assess cardiovascular outcomes after an arterial switch operation between 1983 and 1999. Patients without follow-up visits within 3 years were contacted and secondary sources of information obtained. Overall, 400 patients, 154 (38.3%) with a ventricular septal defect, 238 (59.5%) with an intact septum, and 9 (2.3%) with a Taussig-Bing anomaly, were followed for a median of 18.7 years. In perioperative survivors, overall and arrhythmia-free survival rates at 25 years were 96.7±1.8% and 96.6±0.1%, respectively. Late mortality was predominantly a result of sudden deaths and myocardial infarction. At 25 years, 75.5±2.5% remained free from surgical or catheter-based reintervention. Freedom from an adverse cardiovascular event was 92.9±1.9% at 25 years. Independent predictors were a single right coronary artery (hazard ratio, 4.58; 95% confidence interval, 1.32-15.90), P=0.0166) and postoperative heart failure (hazard ratio, 6.93; 95% confidence interval, 1.57-30.62; P=0.0107). At last follow-up, the left ventricular ejection fraction was 60.3±8.9%, 97.3% had class I symptoms, and 5.2% obstructive coronary artery disease. Peak oxygen uptake was 35.1±7.6 mL/kg/min (86.1±15.1% predicted), with a chronotropic index <80% in 34.2%. At least moderate neoaortic and pulmonary regurgitation were present in 3.4% and 6.6%, respectively, and more than mild neoaortic and pulmonary stenosis in 3.2% and 10.3%. Conclusions— Long-term and arrhythmia-free survival is excellent after arterial switch operation. Although sequelae include chronotropic incompetence and neoaortic, pulmonary, and coronary artery complications, most patients maintain normal systolic function and exercise capacity.

Usefulness of epoprostenol therapy in the severely ill adolescent/adult with Eisenmenger physiology

We showed that in selected severely impaired and symptomatic patients with Eisenmenger physiology, IV-PGI 2 therapy can significantly improve functional capacity, oxygen saturation, and cardiopulmonary hemodynamics. The long-term effects of this agent on morbidity and survival for this population, as well as its complications, remain unknown. A larger controlled prospective multicentered trial should be performed for patients with Eisenmenger physiology who fail conventional therapy and are at the highest risk for significant morbidity and early mortality.

MELD-XI score and cardiac mortality or transplantation in patients after Fontan surgery

Objective The Fontan operation is a staged palliation for complex congenital heart disease and single ventricle physiology. Perioperative survivors of the Fontan operation experience long-term cardiac complications, including death. Liver and renal dysfunction are reported in these patients and have a direct effect on morbidity and mortality. This study aims to investigate whether the Model for End-stage Liver Disease eXcluding INR score (function of creatinine and total bilirubin, MELD-XI) predicts risk for cardiac mortality or transplantation in patients with Fontan circulation. Design and setting Retrospective, single-centre study. Time of first evaluation was the time of the earliest available MELD-XI score measurement, and follow-up was terminated by a cardiac event or by the last clinical evaluation. Patients Patients surviving after Fontan surgery and evaluated at Boston Childrens Hospital between 1993 and 2008. Main outcome measure Composite endpoint of sudden death, death from congestive heart failure or cardiac transplantation. Results The MELD-XI score was calculated as MELD-XI=11.76(loge creatinine)+5.112(loge total bilirubin)+9.44. Ninety-six patients were included (52 male, median age 26 years). After a mean follow-up period of 5.7 years, 18 patients (19%) experienced the composite end point. Baseline MELD-XI score was independently and directly related to the incidence of the composite endpoint (HR for high MELD-XI score group of 7.76, 95% CI 2.05 to 29.33, p=0.008). Conclusions Fontan patients with a higher MELD-XI score have shorter freedom from sudden cardiac death, death from congestive heart failure and cardiac transplantation.

Maternal cardiovascular events during childbirth among women with congenital heart disease

Objectives To define the epidemiology of adverse cardiovascular events among women with congenital heart disease (CHD) hospitalised for childbirth in the USA. Design and setting The 1998–2007 Nationwide Inpatient Sample, an administrative dataset representative of overall US hospital admissions, was used to identify hospitalisations for delivery. Main outcome measures Logistic regression was used to estimate ORs for cardiovascular outcomes (arrhythmia, heart failure, cerebrovascular accident, embolism, death or a combined outcome) for women with and without CHD. Covariates included age, number of medical comorbidites, pulmonary hypertension, hospital teaching status, insurance status and method of delivery. Results Annual deliveries for women with CHD increased 34.9% from 1998 to 2007 compared with an increase of 21.3% in the general population. Women with CHD were more likely to sustain a cardiovascular event (4042/100 000 vs 278/100 000 deliveries, univariate OR 15.1, 95% CI 13.1 to 17.4, multivariable OR 8.4, 95% CI 7.0 to 10.0). Arrhythmia, the most common cardiovascular event, was more frequent among women with CHD (2637/100 000 vs 210/100 000, univariate OR 12.9, 95% CI 10.9 to 15.3, multivariable OR 8.3, 95% CI 6.7 to 10.1). Death occurred in 150/100 000 patients with CHD compared with 8.2/100 000 patients without CHD (multivariable OR 6.7, 95% CI 2.9 to 15.4). Complex CHD was associated with greater odds of having an adverse cardiovascular event than simple CHD (8158/100 000 vs 3166/100 000, multivariable OR 2.0, 95% CI 1.4 to 3.0). Conclusions Maternal CHD is associated with a markedly increased risk of adverse cardiovascular events and death during admission for delivery.

Heart Rate Response During Exercise and Pregnancy Outcome in Women With Congenital Heart Disease

Background— Cardiopulmonary exercise testing is often used to evaluate exercise capacity in adults with congenital heart disease including women who are considering pregnancy. The relationship between cardiopulmonary exercise testing parameters and pregnancy outcome has not been defined. Methods and Results— We conducted a multicenter retrospective observational study of women with congenital heart disease who had undergone cardiopulmonary exercise testing within 2 years of pregnancy or during the first trimester. Cardiopulmonary exercise testing variables included peak oxygen consumption and measures of chronotropic response: peak heart rate, percentage of maximum age predicted heart rate, heart rate reserve (peak heart rate−resting heart rate), and chronotropic index [(peak heart rate−resting heart rate)/(220−age−resting heart rate)]. We identified 89 pregnancies in 83 women. There were 4 spontaneous abortions and 1 termination. One or more adverse cardiac events occurred in 18%; congestive heart failure in 14%, and sustained arrhythmia in 7%. Peak heart rate (odds ratio [OR] 0.71; 95% confidence interval [CI] [0.53, 0.94]; P=0.02), percentage of maximum age predicted heart rate (OR 0.93; 95% CI [0.88, 0.98]; P=0.01), and chronotropic index (OR 0.65; 95% CI [0.47, 0.90]; P=0.01) were associated with a cardiac event. Neonatal events occurred in 20%. Peak heart rate (OR 0.75; 95% CI [0.58, 0.98]; P=0.04), percentage of maximum age predicted heart rate (OR 0.94; 95% CI [0.89, 0.99]; P=0.02), heart rate reserve (OR 0.8; 95% CI [0.64, 0.99]; P=0.04), and chronotropic index (OR 0.73; 95% CI [0.54, 0.98]; P=0.04) correlated with a neonatal event. Peak oxygen consumption was not associated with an adverse pregnancy outcome. Conclusions— Abnormal chronotropic response correlates with adverse pregnancy outcomes in women with congenital heart disease and should be considered in refining risk stratification schemes.