Anne Marie Valente

Arrhythmia Burden in Adults With Surgically Repaired Tetralogy of Fallot A Multi-Institutional Study

Background— The arrhythmia burden in tetralogy of Fallot, types of arrhythmias encountered, and risk profile may change as the population ages. Methods and Results— The Alliance for Adult Research in Congenital Cardiology (AARCC) conducted a multicenter cross-sectional study to quantify the arrhythmia burden in tetralogy of Fallot, to characterize age-related trends, and to identify associated factors. A total of 556 patients, 54.0% female, 36.8±12.0 years of age were recruited from 11 centers. Overall, 43.3% had a sustained arrhythmia or arrhythmia intervention. Prevalence of atrial tachyarrhythmias was 20.1%. Factors associated with intraatrial reentrant tachycardia in multivariable analyses were right atrial enlargement (odds ratio [OR], 6.2; 95% confidence interval [CI], 2.8 to 13.6), hypertension (OR, 2.3; 95% CI, 1.1 to 4.6), and number of cardiac surgeries (OR, 1.4; 95% CI, 1.2 to 1.6). Older age (OR, 1.09 per year; 95% CI, 1.05 to 1.12), lower left ventricular ejection fraction (OR, 0.93 per unit; 95% CI, 0.89 to 0.96), left atrial dilation (OR, 3.2; 95% CI, 1.5 to 6.8), and number of cardiac surgeries (OR, 1.5; 95% CI, 1.2 to 1.9) were jointly associated with atrial fibrillation. Ventricular arrhythmias were prevalent in 14.6% and jointly associated with number of cardiac surgeries (OR, 1.3; 95% CI, 1.1 to 1.6), QRS duration (OR, 1.02 per 1 ms; 95% CI, 1.01 to 1.03), and left ventricular diastolic dysfunction (OR, 3.3; 95% CI, 1.5 to 7.1). Prevalence of atrial fibrillation and ventricular arrhythmias markedly increased after 45 years of age. Conclusions— The arrhythmia burden in adults with tetralogy of Fallot is considerable, with various subtypes characterized by different profiles. Atrial fibrillation and ventricular arrhythmias appear to be influenced more by left- than right-sided heart disease.

Nonalcoholic steatohepatitis : clinicopathological comparison with alcoholic hepatitis in ambulatory and hospitalized patients

This study reports a clinicopathological analysis of 105 patients whose liver histology showed a pattern of alcohol-like steatohepatitis. There were 32 nonalcoholic, 21 asymptomatic ambulatory, and 52 hospitalized alcoholic hepatitis patients. Female sex, obesity, and diabetes predominated in nonalcoholics. Clinical and laboratory presentation were similar in nonalcoholics and ambulatory alcoholics, but different from the hospitalized alcoholics. Histology showed an increasing degree of severity of hepatocellular damage. Mallory bodies, neutrophil and mononuclear infiltration, and pericellular and portal fibrosis from the nonalcoholics to the hospitalized alcoholics, with ambulatory alcoholics displaying an intermediate degree of severity. Steatosis and glycogenated nuclei were prevalent in the obese, diabetic nonalcoholics, of whom 47% had significant fibrosis and 8% cirrhosis, the latter present in 38% and 89% of ambulatory and hospitalized alcoholic hepatitis (P=0.0001), respectively. In asymptomatic subjects with suspected liver disease, a liver biopsy is the only way of establishing the type and severity of liver lesions.

Effects of Regional Dysfunction and Late Gadolinium Enhancement on Global Right Ventricular Function and Exercise Capacity in Patients With Repaired Tetralogy of Fallot

Background— The underlying mechanisms that contribute to global right ventricular (RV) dysfunction in patients with repaired tetralogy of Fallot are incompletely understood. We therefore sought to quantify regional RV abnormalities and to determine the relationship of these to global RV function and exercise capacity. Methods and Results— Clinical and cardiac magnetic resonance data from 62 consecutive patients with repaired tetralogy of Fallot were analyzed (median age at follow-up 23 years [limits 9 to 67 years]). Using cardiac magnetic resonance data, 3D RV endocardial surface models were reconstructed from segmented contours, and a correspondence between end diastole and end systole was computed with a novel algorithm. Regional RV abnormalities were quantified and expressed as segmental ejection fraction, spatial extent of dyskinetic area, displacement of dyskinetic area, and score of extent of late gadolinium enhancement. Regional abnormalities of function and hyperenhancement were greatest in the RV outflow tract (RVOT). These regional RVOT abnormalities correlated with global RV ejection fraction: RVOT ejection fraction r=0.64, P<0.0001; RVOT dyskinetic area r=−0.51, P<0.0001; RVOT displacement of dyskinetic area r=−0.49, P<0.0001; and RVOT late gadolinium enhancement score r=−0.33, P=0.01. Peak oxygen consumption during exercise correlated best with RVOT ejection fraction (r=0.56, P=0.0002) compared with the remainder of the RV (r=0.35, P=0.03). The only cardiac magnetic resonance variable independently predictive of aerobic capacity was RVOT ejection fraction (P=0.02). Conclusion— A greater extent of regional abnormalities in the RVOT adversely affects global RV function and exercise capacity after tetralogy of Fallot repair. These regional measures may have important implications for patient management, including RVOT reconstruction, at the time of pulmonary valve replacement.

Contemporary predictors of death and sustained ventricular tachycardia in patients with repaired tetralogy of Fallot enrolled in the INDICATOR cohort

Objective Patients with repaired tetralogy of Fallot (TOF) experience increased rates of mortality and morbidity in adulthood. This study was designed to identify risk factors for death and ventricular tachycardia (VT) in a large contemporary cohort of patients with repaired TOF. Methods Subjects with repaired TOF from four large congenital heart centres in the USA, Canada and Europe were enrolled. Clinical, ECG, exercise, cardiac magnetic resonance (CMR) and outcome data were analysed. Results Of the 873 patients (median age 24.4 years), 32 (3.7%) reached the primary outcome (28 deaths, 4 sustained VT; median age at outcome 38 years; median time from CMR to outcome 1.9 years). Cox proportional-hazards regression identified RV mass-to-volume ratio ≥0.3 g/mL (HR, 5.04; 95% CI 2.3 to 11.0; p<0.001), LV EF z score<−2.0 (HR, 3.34; 95% CI 1.59 to 7.01; p=0.001), and history of atrial tachyarrhythmia (HR, 3.65; 95% CI 1.75 to 7.62; p=0.001) as outcome predictors. RV dysfunction was predictive of the outcome similar to LV dysfunction. In subgroup analysis of 315 subjects with echocardiographic assessment of RV systolic pressure, higher pressure (HR 1.39; 95% CI 1.19 to 1.62; p<0.001) was associated with death and sustained VT independent of RV hypertrophy and LV dysfunction. Conclusions RV hypertrophy, ventricular dysfunction and atrial tachyarrhythmias are predictive of death and sustained VT in adults with repaired TOF. These findings may inform risk stratification and the design of future therapeutic trials.

Multimodality Imaging Guidelines for Patients with Repaired Tetralogy of Fallot: A Report from the American Society of Echocardiography Developed in Collaboration with the Society for Cardiovascular Magnetic Resonance and the Society for Pediatric Radiology

1. Executive Summary 112 Goals of Imaging 112 Imaging Modalities 112 Echocardiography 113 CMR 113 Cardiovascular CT 113 Nuclear Scintigraphy 113 X-Ray Angiography 113 Multimodality Imaging 113 2. Background 113 3. General Considerations 114 4. Goals of Imaging 114 5. Echocardiography 114 a. Overview of Modality 114 b. Strength and Limitations 115 c. Assessment of Repaired TOF with Echocardiography 115 RVOT 115 PAs 115

Prevalence of Left Ventricular Systolic Dysfunction in Adults With Repaired Tetralogy of Fallot

Left ventricular (LV) systolic dysfunction has been observed in patients with repaired tetralogy of Fallot (TOF), although its clinical associations are unknown. Adults with repaired TOF were identified from 11 adult congenital heart disease centers. Clinical history was reviewed. Patients with pulmonary atresia were excluded. Echocardiograms were reanalyzed to estimate LV ejection fraction. LV function was defined as normal (LV ejection fraction ≥ 55%) or mildly (45% to 54%), moderately (35% to 44%), or severely (< 35%) decreased. Right ventricular (RV) and LV dimensions and Doppler parameters were remeasured. Function of all valves was qualitatively scored. Of 511 patients studied, LV systolic dysfunction was present in 107 (20.9%, 95% confidence interval 17.4 to 24.5). Specifically, 74 (14.4%) had mildly decreased and 33 (6.3%) had moderately to severely decreased systolic function. Presence of moderate to severe LV dysfunction was associated with male gender, LV enlargement, duration of shunt before repair, history of arrhythmia, QRS duration, implanted cardioverter-defibrillator, and moderate to severe RV dysfunction. Severity or duration of pulmonary regurgitation was not different. In conclusion, LV systolic dysfunction was found in 21% of adult patients with TOF and was associated with shunt duration, RV dysfunction, and arrhythmia.

Evaluating Failing Fontans for Heart Transplantation: Predictors of Death

BACKGROUND Late complications of the Fontan operation represent a significant management challenge. Failing Fontan patients have two modes of presentation: impaired ventricular function (IVF) and those with preserved ventricular function (PVF) but with failing Fontan physiology (protein-losing enteropathy [PLE] and plastic bronchitis [PB]). This study evaluated whether failing Fontan patients referred for heart transplantation had a different outcome based on the mode of presentation. METHODS The medical records of all Fontan patients evaluated for heart transplantation at a single institution from 1994 to 2008 were retrospectively reviewed. Demographic, hemodynamic, and laboratory data were collected. Patients were stratified into an IVF or PVF group by echocardiographic criteria. Descriptive statistics and Kaplan-Meier analysis were used for hypothesis testing. RESULTS Thirty-four Fontan patients were evaluated for heart transplantation. According to echo description of systolic function, 18 were categorized as IVF and 16 as PVF. The IVF group had a significantly lower cardiac index and venous oxygen saturation, and significantly higher systemic vascular resistance vs the PVF group (p < 0.05). PLE or PB was present in 13 PVF patients and none in the IVF group. Twenty patients underwent transplantation, with similar rates amongst the IVF and PVF groups. Within 1 year from evaluation, 2 IVG patients and 7 PVF patients had died (p = 0.052). CONCLUSIONS Failing Fontan patients with PVF have decreased overall survival independent of whether they underwent transplantation. This trend indicates a need to improve the management and timing for transplantation amongst this population.

Prevalence and predictors of gaps in care among adult congenital heart disease patients: HEART-ACHD (The Health, Education, and Access Research Trial)

OBJECTIVES The goal of this project was to quantify the prevalence of gaps in cardiology care, identify predictors of gaps, and assess barriers to care among adult congenital heart disease (adult CHD) patients. BACKGROUND Adult CHD patients risk interruptions in care that are associated with undesired outcomes. METHODS Patients (18 years of age and older) with their first presentation to an adult CHD clinic completed a survey regarding gaps in, and barriers to, care. RESULTS Among 12 adult CHD centers, 922 subjects (54% female) were recruited. A >3-year gap in cardiology care was identified in 42%, with 8% having gaps longer than a decade. Mean age at the first gap was 19.9 years. The majority of respondents had more than high school education and knew their heart condition. The most common reasons for gaps included feeling well, being unaware that follow-up was required, and complete absence from medical care. Disease complexity was predictive of a gap in care with 59% of mild, 42% of moderate, and 26% of severe disease subjects reporting gaps (p < 0.0001). Clinic location significantly predicted gaps (p < 0.0001), whereas sex, race, and education level did not. Common reasons for returning to care were new symptoms, referral from provider, and desire to prevent problems. CONCLUSIONS Adult CHD patients have gaps in cardiology care; the first lapse commonly occurred at age ∼19 years, a time when transition to adult services is contemplated. Gaps were more common among subjects with mild and moderate diagnoses and at particular locations. These results provide a framework for developing strategies to decrease gaps and address barriers to care in the adult CHD population.

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.

Liver Disease in the Patient with Fontan Circulation

The Fontan procedure has undergone many modifications since first being performed on a patient with tricuspid valve atresia in 1968. It is now the procedure of choice for individuals born with single-ventricle physiology or for those in whom a biventricular repair is not feasible. Forty years of experience with the Fontan procedure have gradually revealed the shortfalls of such a circulatory arrangement. Sequelae related to the underlying congenital anomaly or to the altered physiology of passive, nonpulsatile flow through the pulmonary arterial bed can result in failure of the Fontan circulation over time. Liver abnormalities including abnormalities in the clotting cascade have been well documented in Fontan patients. The clinical significance of these findings, however, has remained poorly understood. As Fontan survivors have increased in age and number, we have begun to better recognize subclinical hepatic dysfunction and the contribution of liver disease to adverse outcomes in this population. The purpose of this review is to summarize the existing data pertaining to liver disease in the Fontan population and to identify some questions that have yet to be answered.