Dextro-Transposition of the Great Arteries Long-term Sequelae of Atrial and Arterial Switch CARDIOLOGY CLINICS 2015; 33 (4): 543-?
Rapid, High-Quality, Cost-Effective, Comprehensive and Expandable Targeted Next-Generation Sequencing Assay for Inherited Heart Diseases CIRCULATION RESEARCH 2015; 117 (7): 603-611
Thousands of mutations across more than 50 genes have been implicated in inherited cardiomyopathies. However, options for sequencing this rapidly evolving gene set are limited as many sequencing services and off-the-shelf kits suffer from slow turnaround, inefficient capture of genomic DNA, and/or high cost. Furthermore, customization of these assays to cover emerging targets and to suit individual needs is often expensive and time-consuming.We sought to develop a custom high throughput, clinical-grade next generation sequencing (NGS) assay for detecting cardiac disease gene mutations with improved accuracy, flexibility, turnaround, and cost.We employed double-stranded probes (complementary long "padlock" probes (cLPPs)), an inexpensive and customizable capture technology, to efficiently capture and amplify the entire coding region and flanking intronic and regulatory sequences of 88 genes and 40 microRNAs (miRNA) associated with inherited cardiomyopathies, congenital heart disease (CHD), and cardiac development. Multiplexing 11 samples per sequencing run resulted in a mean base coverage of 420, of which 97% had >20X coverage and >99% were concordant with known heterozygous single nucleotide polymorphisms (SNPs). The assay correctly detected germline variants in 24 individuals and revealed several polymorphic regions in miR-499. Total run time was three days at an approximate cost of $100 per sample.Accurate, high throughput detection of mutations across numerous cardiac genes is achievable with cLPP technology. Moreover, this format allows facile insertion of additional probes as more cardiomyopathy and CHD genes are discovered, giving researchers a powerful new tool for DNA mutation detection and discovery.
View details for DOI 10.1161/CIRCRESAHA.115.306723
View details for Web of Science ID 000360967000006
Predicting Outcomes Using the Heart Failure Survival Score in Adults with Moderate or Complex Congenital Heart Disease. Congenital heart disease 2015; 10 (5): 387-395
Adults with congenital heart disease (CHD) face increased risk for morbidity and mortality with age, but few prognostic models exist.This study aims to assess whether the Heart Failure Survival Score (HFSS), which risk stratifies patients for heart transplantation, predicts outcomes in adults with moderate or complex CHD.This was a multicenter, retrospective study which identified 441 patients with moderate or complex CHD between 2005 and 2013, of whom 169 had all the HFSS parameters required to calculate the risk score. Because all study patients were deemed low risk by the HFSS, the score was dichotomized at the median (10.4). Outcomes included death, transplant or ventricular assist device (VAD), arrhythmia requiring treatment, nonelective cardiovascular (CV) hospitalizations, and the composite. Associations of mean HFSS and HFSS <10.4 with each outcome were assessed.The cohort had mean standard deviation age of 33.6 12.6 years, peak VO2 21.8 7.5mL/kg/min, HFSS of 10.45 0.88, and median years follow-up of 2.7 (1.1, 5.2). There were five deaths (2.8%), no transplants or VADs, 25 arrhythmias (14.8%), 22 CV hospitalizations (13%), and 39 composites (23.1%). Lower mean HFSS was observed for patients who died (9.6 0.83 vs. 10.5 0.87, P = .02), arrhythmia requiring treatment (10.0 0.70 vs. 10.5 0.89, P = .005), CV hospitalizations (9.9 0.73 vs. 10.5 0.88, P = .002), and the composite (10.0 0.70 vs. 10.6 0.89, P < .001). The positive and negative predictive values of HFSS <10.4 for the composite were 34% and 88% respectively, with sensitivity and specificity 74% and 56%.Although a low HFSS was significantly associated with outcomes, it did not adequately risk stratify adults with CHD, whose heterogeneous pathophysiology differs from that of the acquired heart failure population. Further studies are warranted to provide a more accurate prognosis.
View details for DOI 10.1111/chd.12229
View details for PubMedID 25358483
Left Ventricular Retraining and Late Arterial Switch for D-Transposition of the Great Arteries ANNALS OF THORACIC SURGERY 2015; 99 (5): 1655-1663
Heart Murmur and Physical Examination in Athletes with a Focus on Congenital Heart Disease CURRENT SPORTS MEDICINE REPORTS 2015; 14 (3): 263-265
Management of Cardiovascular Risk Factors in Adults With Congenital Heart Disease JOURNAL OF THE AMERICAN HEART ASSOCIATION 2014; 3 (6)
Usefulness of the Seattle Heart Failure Model to identify adults with congenital heart disease at high risk of poor outcome. American journal of cardiology 2014; 113 (5): 865-870
Our objective was to determine whether the Seattle Heart Failure Model (SHFM) differentiates patients with adult congenital heart disease (ACHD) at high versus low risk for cardiovascular outcomes and poor exercise capacity. The ACHD population is growing and presents increasingly for care in the community and at tertiary centers. Few strategies exist to identify the patients with ACHD at high risk for heart failure and mortality.We studied 153 adults with transposition of the great arteries, Ebstein anomaly, tetralogy of Fallot, double outlet right ventricle, and single ventricle from 2 ACHD centers. The primary outcome was cardiovascular death, with a secondary composite outcome of death, transplant, ventricular assist device, cardiovascular admission, and treatment for arrhythmia. We defined risk groups based on SHFM 5-year predicted survival: high (predicted survival <70%), intermediate (70% to 85%), and low risk (>85%). Ten patients had the primary outcome of death, and 46 the combined end point. The hazard of death in the SHFM high- versus the intermediate-risk group was 7.09 (95% confidence interval 1.5 to 33.4, p= 0.01; no deaths in the low-risk group) and the hazard of the composite outcome between the high- versus low-risk group was 6.64 (95% confidence interval 2.5 to 17.6, p= 0.0001). Kaplan-Meier survival analysis showed greater probability of all-cause mortality (p= 0.003) in the high-risk group. In conclusion, the SHFM can help identify subjects with ACHD at risk for adverse outcome and poor cardiopulmonary efficiency. This may add to the care of patients with ACHD in the community and streamline care at tertiary centers.
View details for DOI 10.1016/j.amjcard.2013.11.043
View details for PubMedID 24411285
Coarctation of the aorta associated with Dandy-Walker variant. Journal of cardiovascular disease research 2013; 4 (3): 182-186
This article reports a rare case of coarctation of the aorta associated with Dandy-Walker variant in a 17-year-old girl. Differential diagnoses of coarctation of the aorta and Dandy-Walker variant are extensively discussed. In addition, standard surgical treatment of coarctation as well as new approaches such as endovascular stenting are described in detail to provide therapeutic insights into her management. Although surgical or endovascular repair of coarctation results in significant improvement of systemic hypertension and is associated with better survival, cardiovascular complications are still very common. Thus, long-term follow-up after repair is required, and high-quality imaging studies such as echocardiography, CT and MRI are warranted.
View details for DOI 10.1016/j.jcdr.2013.06.002
View details for PubMedID 24396258
Anti-thrombotic strategies in the third trimester of pregnancy: A case of spontaneous coronary dissection requiring emergent PCI INTERNATIONAL JOURNAL OF CARDIOLOGY 2013; 167 (1): E22-E25
Caring for the Adult with Congenital Heart Disease in an Adult Catheterization Laboratory by Pediatric InterventionalistsSafety and Efficacy CONGENITAL HEART DISEASE 2013; 8 (2): 111-116
The purpose of this study is to describe the outcomes of cardiac catheterizations performed by pediatric interventional cardiologists in an adult catheterization laboratory on adult patients with congenital heart disease (CHD).With improved survival rates, the number of adults with CHD increases by ?5%/year; this population often requires cardiac catheterization.From January 2005 to December 2009, two groups of patients were identified, an adult group (>21 years) and an adolescent group (13-21 years), who had catheterizations performed by pediatric interventional staff.Fifty-seven catheterizations were performed in 53 adults, while 59 were performed in 47 adolescents. The male to female ratio differed significantly between groups; only 15/53 (28%) of adults were male vs. 26/47 (55%) of adolescents (P =.006). Among adults, 27 had previously corrected CHD, 16 with atrial septal defect (ASD), and six with patent foramen ovale (PFO). This differed significantly from the adolescents, where only 30 had previously corrected CHD, seven with ASD, and one with PFO (P =.012). Among adults who were catheterized, interventions were performed on 28/53 (53%). All interventions were successful and included ASD/PFO closure, patent ductus arteriosus occlusion, coarctation dilation, pulmonary artery dilations, and one saphenous vein graft aneurysm closure. Nineteen adults had coronary angiography performed by adult interventionalists in consult with pediatric interventionalists. Two complications occurred among adults (3.8%) vs. one complication (2%; P = 1) among adolescents. No femoral vessel complications or catheterization-associated mortality occurred.Cardiac catheterizations can be performed effectively and safely in adults with CHD by pediatric interventional cardiologists in an adult catheterization laboratory.
View details for DOI 10.1111/chd.12004
View details for Web of Science ID 000317140100013
View details for PubMedID 23006871
Aortic Root Dilatation in Adults with Surgically Repaired Tetralogy of Fallot A Multicenter Cross-Sectional Study CIRCULATION 2013; 127 (2): 172-?
Although aortic root pathology has been described in patients with tetralogy of Fallot, the scope of the problem remains poorly defined. We sought to determine the prevalence and predictors of aortic root dilatation in adults with repaired tetralogy of Fallot.A multicenter cross-sectional study was conducted with standardized reassessment of echocardiographic parameters in 474 adults (?18 years) with surgically repaired tetralogy of Fallot or pulmonary atresia with ventricular septal defect. The aortic root was measured in a parasternal long-axis view, in diastole, at the level of the sinus of Valsalva. Prevalence and predictors of an absolute diameter ?40 mm and of an observed-to-expected ratio >1.5 were assessed. The aortic root dimension was ?40 mm in 28.9% (95% confidence interval, 26.9%-30.9%). In multivariate analyses, the only independently associated factor was male sex (odds ratio, 4.48; 95% confidence interval, 1.55-12.89; P=0.006). The prevalence of an observed-to-expected aortic root dimension ratio >1.5 was 6.6% (95% confidence interval, 5.3%-7.9%). It was associated with pulmonary atresia and moderate or severe aortic regurgitation in univariate analyses, but no independent predictor was identified. The side of the aortic arch was not associated with aortic root dimension. The prevalence of moderate or severe aortic regurgitation was 3.5% (95% confidence interval, 2.7%-4.2%).Although nearly one third of adults with repaired tetralogy of Fallot have an aortic root diameter ?40 mm, the prevalence of a dilated aortic root, when defined by an indexed ratio of observed-to-expected values, is low. Similarly, moderate or severe aortic regurgitation is uncommon.
View details for DOI 10.1161/CIRCULATIONAHA.112.129585
View details for Web of Science ID 000313637200013
View details for PubMedID 23224208
Left and Right Ventricular Diastolic Function in Adults With Surgically Repaired Tetralogy of Fallot: A Multi-Institutional Study. The Canadian journal of cardiology 2013
BACKGROUND: Our purpose was to assess the prevalence and clinical implications of left ventricular (LV) and right ventricular (RV) diastolic dysfunction (DD) in patients with repaired tetralogy of Fallot (TOF). METHODS: Adults with repaired TOF at 11 North American congenital heart disease centres were included. Of 556 patients analyzed, 325 had sufficient Doppler data to evaluate for LV DD, defined as mitral lateral e' < 10 cm/s and E/e' ratio > 9. Abnormal RV diastolic function was defined as tricuspid E/A ratio of 0.8 to 2.1 with E/e' ratio > 6 or a tricuspid ratio E/A > 2.1 with a deceleration time < 120 milliseconds, and 105 patients were found to have sufficient Doppler data. RESULTS: Abnormal LV diastolic Doppler indices were prevalent in 13.8% and associated with hypertension, dyslipidemia, 3 or more cardiac operations, and a history of ventricular tachycardia. Abnormal RV indices were prevalent in 52.4% and associated with hypertension, dyslipidemia, diabetes mellitus, and 3 or more cardiac operations. Ventricular tachycardia was more common in those with abnormal RV diastolic function. CONCLUSION: Further prospective studies are needed to evaluate these associations with DD and the impact of treatment risk factors on diastolic function and arrhythmia burden.
View details for PubMedID 23369488
Not All Obstructive Cardiac Lesions Are Created Equal: Double-Chamber Right Ventricle In Pregnancy ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES 2012; 29 (8): E197-E200
Double-chambered right ventricle (DCRV) is a rare form of right ventricular outflow tract (RVOT) obstruction accounting for approximately 1% of patients with congenital heart disease. It consists of an anomalous muscle bundle that divides the right ventricle usually between the sinus (inlet) and the infundibulum (outlet). This division creates a proximal chamber with high pressure and a distal chamber with low pressure. The hemodynamic obstruction of the RVOT is usually an acquired phenomenon, however the substrate for the anomalous muscle bundle is likely congenital. The diagnosis of DCRV should be considered in the young patient with an elevated right ventricular systolic pressure and intracavitary gradient. Echocardiography and cardiac MRI are the principal diagnostic tools for the assessment of DCRV. This entity is often misdiagnosed as pulmonary hypertension in the young patient, and can often go overlooked and untreated for many years. Definitive therapy involves surgical resection of the muscle bundle. This can often be curative and if done in a timely fashion, may prevent right ventricular remodeling. We describe the unique diagnostic dilemma, the course and management of a young adult with DCRV during pregnancy.
View details for DOI 10.1111/j.1540-8175.2012.01721.x
View details for Web of Science ID 000308466700006
View details for PubMedID 22639818
Making Complex Adult Congenital Heart Disease a Little Simpler SEMINARS IN ROENTGENOLOGY 2012; 47 (3): 289-301
Prevalence of Left Ventricular Systolic Dysfunction in Adults With Repaired Tetralogy of Fallot AMERICAN JOURNAL OF CARDIOLOGY 2011; 107 (8): 1215-1220
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.
View details for DOI 10.1016/j.amjcard.2010.12.026
View details for Web of Science ID 000289702400019
View details for PubMedID 21349477
Heart Rate Response During Exercise and Pregnancy Outcome in Women With Congenital Heart Disease CIRCULATION 2011; 123 (3): 242-248
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.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.Abnormal chronotropic response correlates with adverse pregnancy outcomes in women with congenital heart disease and should be considered in refining risk stratification schemes.
View details for DOI 10.1161/CIRCULATIONAHA.110.953380
View details for Web of Science ID 000286507800010
View details for PubMedID 21220738
Arrhythmia Burden in Adults With Surgically Repaired Tetralogy of Fallot A Multi-Institutional Study CIRCULATION 2010; 122 (9): 868-875
The arrhythmia burden in tetralogy of Fallot, types of arrhythmias encountered, and risk profile may change as the population ages.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.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.
View details for DOI 10.1161/CIRCULATIONAHA.109.928481
View details for Web of Science ID 000281502900004
View details for PubMedID 20713900
The CALF (Congenital Heart Disease in Adults Lower Extremity Systemic Venous Health in Fontan Patients) Study JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2010; 56 (2): 144-150
The objective of this study was to document the prevalence of chronic venous insufficiency (CVI) and its associated factors in adults with Fontan physiology.As the population of adults with complex congenital heart disease and Fontan physiology increases, so does the occurrence of highly morbid and mortal outcomes, including heart failure and thromboembolism. The presence of abnormal peripheral hemodynamic conditions in this population and their potential contribution to adverse outcomes is not well known. The primary objective of this study was to document the prevalence of CVI in adults with Fontan physiology.A total of 159 adults with Fontan physiology from 7 adult congenital heart centers were prospectively assessed for lower extremity CVI, with the assignment of clinical, etiological, anatomical, and pathophysiological classification grades, and compared with age-matched and sex-matched controls. Leg photographs were independently reassessed to confirm interobserver reliability.The prevalence of CVI was significantly greater in the Fontan population (60%; 95% confidence interval [CI]: 52% to 68%) compared with healthy controls (32%; 95% CI: 15% to 54%) (p = 0.008). Strikingly, the prevalence of severe CVI (clinical, etiological, anatomical, and pathophysiological grade > or = 4) was significantly higher in the Fontan group (22%; 95% CI: 16% to 29%) versus the healthy controls (0%; 95% CI: 0% to 14%) (p = 0.005). In a multivariate analysis, several factors were independently associated with severe CVI, including increased numbers of catheterizations with groin venous access, lower extremity itching, and deep venous thrombosis.CVI is common in adult patients with congenital heart disease with Fontan physiology. The contribution of abnormal peripheral hemodynamic conditions to comorbidities, including thromboembolism and heart failure, and interventions to improve peripheral hemodynamic conditions require further exploration.
View details for DOI 10.1016/j.jacc.2010.02.048
View details for Web of Science ID 000279313600009
View details for PubMedID 20620728