Dhaval R. Parekh

Outcomes of Heart Failure–Related Hospitalization in Adults with Congenital Heart Disease in the United States

BACKGROUND Heart failure (HF) accounts for >3 million hospital admissions annually in adults with acquired cardiovascular disease, but there are limited data on HF admissions in adults with congenital heart disease (ACHD). The purpose of this study was to test the hypotheses that HF admissions are common in ACHD and associated with significant morbidity and mortality. METHODS The 2007 Nationwide Inpatient Sample was used to assess national prevalence, morbidities, and risk factors for mortality during hospitalizations among ACHD with HF. RESULTS Of the 84,308 (95% CI 71,345-97,272) ACHD admissions in the United States in 2007, 17,193 (95% CI 14,157-20,229) had a diagnosis of HF (20%). ACHD with HF was associated with an increased risk of death compared to ACHD without HF (OR 3.3, 95% CI 2.6-4.1). On multivariable analysis independent risk factors for mortality included nonoperative intubation (OR 6.1, 95% CI 3.3-11.4), sepsis (OR 4.3, 95% CI 2.4-7.4), and acute myocardial infarction (OR 3.2, 95% CI 1.8-5.7). Cardiac defects associated with an increased risk of mortality included ventricular septal defects (VSDs) (OR 1.8, 95% CI 1.0-3.4). CONCLUSIONS In this large population-based study, HF-related hospitalizations were common in ACHD and associated with an increased risk of death compared to non-HF admissions. The risk of mortality is increased with the diagnoses of VSDs and the presence of specific comorbidities such as respiratory failure and sepsis.

Outcomes of Hospitalization in Adults in the United States With Atrial Septal Defect, Ventricular Septal Defect, and Atrioventricular Septal Defect

Atrial septal defect, ventricular septal defect (VSD), and atrioventricular septal defect (AVSD) are among the most common congenital heart lesions, with most children surviving to adulthood. However, the clinical course of these patients is largely unknown, particularly pertaining to inpatient care. The purpose of this study was to assess hospitalizations for septal defects in adults with congenital heart disease (CHD) and risk factors associated with significant morbidity and mortality. The 2007 Nationwide Inpatient Sample was used to assess national prevalence of hospitalizations in adults with CHD with septal defects. Co-morbidities and risk factors for mortality were also determined. There were 84,308 adult CHD admissions in the United States in 2007. Fifty-four percent of adult CHD admissions had diagnoses of septal defects, with 48% having atrial septal defect, 7% having VSD, and 0.4% having AVSD. Overall in-hospital mortality was 2.1%. Common co-morbidities included arrhythmias (31%), heart failure (20%), and diabetes mellitus (18%). On multivariable analysis, independent risk factors for mortality included presence of VSD (odds ratio 3.1, 95% confidence interval [CI] 1.5 to 6.5), trisomy 21 (odds ratio 2.9, 95% CI 1.1 to 7.5), and pulmonary hypertension (odds ratio 1.5, 95% CI 1.0 to 2.4). In conclusion, this study of hospitalizations in adults with septal defects found that admissions are common and associated with significant co-morbidities. Overall mortality is low but is increased in patients with VSD. Cardiac and noncardiac co-morbidities are commonly encountered. Many noncardiac conditions, including trisomy 21 and the youngest and oldest groups, are associated with an increased risk of death.

Clinical outcomes after ventricular assist device implantation in adults with complex congenital heart disease

BACKGROUND There are minimal data regarding ventricular assist device (VAD) implantation in adult patients with complex congenital heart disease (CHD). METHODS The medical records of 6 adult patients with complex CHD who underwent VAD implantation were retrospectively analyzed to characterize pre-operative clinical status, implantation techniques and challenges, post-operative management, and post-operative outcomes. RESULTS All patients had a systemic right ventricle, including 2 with single-ventricle physiology. The average age at VAD implantation was 41 years. The implanted VADs included 1 HeartMate XVE, 3 HeartMate II (Thoratec Corp, Pleasanton, CA), 1 Jarvik 2000 (Jarvik Heart, New York, NY), and 1 HeartWare HVAD (HeartWare Inc, Framingham, MA). In-hospital outcomes included no sub-pulmonic ventricular failure, no VAD thrombosis or mechanical failure, 30-day mortality in 1 patient, non-fatal sub-arachnoid hemorrhage in 1 patient, and sustained ventricular tachycardia requiring unsynchronized direct current cardioversion in 1 patient. Of the 5 patients who survived to discharge, 1 patient received 171 days of VAD support before cardiac transplantation and survived for 1,484 days after transplantation; 1 patient received 262 days of VAD support before out-of-hospital death of unknown etiology; 1 patient had received VAD support for 988 days as of December 1, 2012, while awaiting a transplant; and 2 patients who received VADs as destination therapy had received 577 and 493 days of VAD support, respectively, and were still alive as of December 1, 2012. CONCLUSIONS This case series characterizes important post-operative management challenges and clinical outcomes associated with VAD implantation as a bridge-to-transplant or as destination therapy in adult patients with complex CHD.

Contemporary Results of Aortic Coarctation Repair Through Left Thoracotomy

BACKGROUND Although surgical results for repair of coarctation of the aorta (CoA) have steadily improved, management of this condition remains controversial. The purposes of this study were to analyze the long-term outcomes of patients undergoing CoA repair through left thoracotomy and to define risk factors for reintervention. METHODS All patients who were less than 18 years old and who underwent initial repair of CoA through left thoracotomy from 1995 to 2013 at Texas Childrens Hospital (Houston, TX) were included. Patients were classified into 3 groups: 143 (42%) neonates (0 to 30 days old), 122 (36%) infants (31 days to 1 year old), and 78 (23%) older children (1 to 18 years old). Univariate and multivariate analyses were performed. RESULTS A total of 343 patients (129 [38%] girls) with median age of 53 days (interquartile range [IQR],12 days to 9 months) and weight of 4.1 kg (IQR, 3.1 to 8.0) underwent repair with extended end-to-end anastomosis (291 patients [85%]), end-to-end anastomosis (44 patients [13%]), interposition graft (2 patients [0.6%]), or subclavian flap (6 patients [2%]). Concomitant diagnoses included genetic abnormalities (48 patients [14%]), isolated ventricular septal defects (58 patients [17%]), small left-sided structures (53 patients,16%), or other complex congenital heart disease (18 patients [5%]). Perioperative mortality was 1% (n = 4, all neonates). At a median follow-up of 6 years (7 days to 19 years), only 14 (4%) patients required reintervention (10 catheter-based procedures, 6 surgical repairs). A postoperative peak velocity of 2.5 m/s or greater was an independent risk factor for reintervention (odds ratio [OR], 4.0; 95% confidence interval [CI], 1.4 to 11.6). Within the cohort, 95 (33%) patients were hypertensive or remained on cardiac medications a median of 12 years (6 months to 19 years) after the surgical procedure. Development of perioperative hypertension was associated with higher risk of chronic hypertension or cardiac medication dependency (OR, 1.9; 95% CI, 1.1 to 3.3). CONCLUSIONS CoA repair through left thoracotomy is associated with low rates of morbidity, mortality, and reintervention. Aortic arch obstruction should be completely relieved at the time of surgical intervention to minimize the risk of long-term recoarctation.

Neurocognitive and executive functioning in adult survivors of congenital heart disease.

OBJECTIVE Congenital heart disease (CHD) can affect the developing central nervous system, resulting in neurocognitive and behavioral deficits. Preoperative neurological abnormalities as well as sequelae of the open heart operations required to correct structural abnormalities of the heart contribute to these deficits. There are few studies examining the neurocognitive functioning of adults with CHD. This study sought to investigate multiple domains of neurocognitive functioning in adult survivors of CHD who had childhood cardiac surgery with either moderate or severe disease complexity. DESIGN A total of 48 adults (18-49 years of age) who had undergone cardiac surgery for CHD prior to five years of age participated in the study. CHD severity was classified as moderate or severe according to the 32nd Bethesda Guidelines. A computerized battery of standardized neurocognitive tests (CNS-Vital Signs), a validated rating scale of executive functioning, and demographic questionnaires were administered. RESULTS There were no significant differences between the moderate CHD group and normative data on any cognitive measure. In contrast, the severe CHD group differed from norms in multiple domains: psychomotor speed, processing speed, complex attention, reaction time, and on the overall neurocognitive index. Number of surgeries was strongly related to worse executive functioning. There was no association between age at first surgery or time since last surgery and neuropsychological functioning. Number of surgeries was also unrelated to neurocognitive test performance. CONCLUSIONS Patients with severe CHD performed significantly worse on measures of processing speed, attention, and executive functioning. These findings may be useful in the long-term care of adults with congenital heart disease.

Left Ventricular Hemodynamic Changes and Clinical Outcomes after Transcatheter Atrial Septal Defect Closure in Adults

OBJECTIVES The objectives of this study are to assess current management algorithms for left ventricular (LV) hemodynamic and diastolic changes following atrial septal device occlusion in adult patients. BACKGROUND Percutaneous closure is now routine for atrial septal defects (ASDs). Previous studies show ventricular size normalization following percutaneous closure. Case reports have discussed the incidence of early LV dysfunction following ASD device placement with some recommending delay of closure or placement of a fenestrated device in patients with elevated LV pressures. METHOD All adult patients with an isolated secundum ASD who underwent percutaneous repair were included in this study. In addition to placement of the Amplatzer septal occluder, all patients had a pre and postprocedure transthoracic echocardiography performed measuring myocardial performance index (MPI). Left ventricular end diastolic pressure (LVEDP) was measured before and after balloon occlusion. RESULTS Nineteen patients (17 female and two male) were included in this study. Average age was 47.2 years (± 12.7 years). All defects were of clinical significance with average Qp : Qs = 2.0 (± 0.6). Balloon occlusion led to a significant (P < .01) increase in LVEDP (pre-LVEDP mean = 7.1 mm Hg, post-LVEDP mean = 15.3 mm Hg). There was no significant change in MPI. ASD device size displayed a modest correlation relative to the change in LVEDP (R = 0.42, P = .09). CONCLUSIONS Percutaneous ASD closure induces an increase in LVEDP. Despite this, all patients tolerated device closure without complication. It appears safe to close ASDs in these patients.

Whole exome sequencing in 342 congenital cardiac left sided lesion cases reveals extensive genetic heterogeneity and complex inheritance patterns

BackgroundLeft-sided lesions (LSLs) account for an important fraction of severe congenital cardiovascular malformations (CVMs). The genetic contributions to LSLs are complex, and the mutations that cause these malformations span several diverse biological signaling pathways: TGFB, NOTCH, SHH, and more. Here, we use whole exome sequence data generated in 342 LSL cases to identify likely damaging variants in putative candidate CVM genes.MethodsUsing a series of bioinformatics filters, we focused on genes harboring population-rare, putative loss-of-function (LOF), and predicted damaging variants in 1760 CVM candidate genes constructed a priori from the literature and model organism databases. Gene variants that were not observed in a comparably sequenced control dataset of 5492 samples without severe CVM were then subjected to targeted validation in cases and parents. Whole exome sequencing data from 4593 individuals referred for clinical sequencing were used to bolster evidence for the role of candidate genes in CVMs and LSLs.ResultsOur analyses revealed 28 candidate variants in 27 genes, including 17 genes not previously associated with a human CVM disorder, and revealed diverse patterns of inheritance among LOF carriers, including 9 confirmed de novo variants in both novel and newly described human CVM candidate genes (ACVR1, JARID2, NR2F2, PLRG1, SMURF1) as well as established syndromic CVM genes (KMT2D, NF1, TBX20, ZEB2). We also identified two genes (DNAH5, OFD1) with evidence of recessive and hemizygous inheritance patterns, respectively. Within our clinical cohort, we also observed heterozygous LOF variants in JARID2 and SMAD1 in individuals with cardiac phenotypes, and collectively, carriers of LOF variants in our candidate genes had a four times higher odds of having CVM (odds ratio = 4.0, 95% confidence interval 2.5–6.5).ConclusionsOur analytical strategy highlights the utility of bioinformatic resources, including human disease records and model organism phenotyping, in novel gene discovery for rare human disease. The results underscore the extensive genetic heterogeneity underlying non-syndromic LSLs, and posit potential novel candidate genes and complex modes of inheritance in this important group of birth defects.

Extracorporeal Membrane Oxygenation Support in Severe Hypertrophic Obstructive Cardiomyopathy Associated With Persistent Pulmonary Hypertension in an Infant of a Diabetic Mother

A male infant was delivered at 37 weeks of gestation via cesarean delivery because of minimal fetal heart tone variability and late fetal decelerations to a 31-year-old mother whose pregnancy was complicated by maternal type 2 diabetes mellitus and chronic hypertension. Fetal echocardiography had been performed at 20 weeks of gestation, which showed a structurally normal heart without ventricular hypertrophy (Figure 1 and Movie IA and IB in the online-only Data Supplement). The mother had been treated previously with insulin, and during pregnancy, had hemoglobin A1c of 7.9% (diabetic patients with adequate glycemic control have values <7% to 8%).1 The birth weight was 4.8 kilograms. The infant developed respiratory failure within the first 15 minutes of life, requiring intubation and mechanical ventilation. The umbilical cord venous blood gas demonstrated a pH of 7.16 and partial pressure of oxygen of 31 mm Hg. A transthoracic echocardiogram (TTE) was performed following the patient’s admission to the neonatal intensive-care unit because of auscultation of a grade-IV/VI harsh systolic ejection murmur heard throughout the precordium. TTE showed severe biventricular hypertrophy, mild right ventricular outflow tract obstruction, severe left ventricular outflow tract obstruction with a …

Electrophysiology procedures in adults with congenital heart disease.

BACKGROUND In adult congenital heart disease (CHD), arrhythmias contribute significantly to morbidity and mortality. Often, these adult patients are treated at a freestanding pediatric facility. Limited data exist looking at this cohort. METHODS A retrospective review was performed of all electrophysiology (EP) procedures performed in adults at our institution during a 5-year period from January 1, 2006 through December 31, 2010. RESULTS There were 99 cases performed in a total of 87 adults with CHD during this time period. The mean patient age was 27.1 years (18-51 years). The most common congenital cardiac diagnoses were: 27% with D-transposition of the great arteries (n = 27)-of which 85% (n = 23) have had a previous atrial switch procedure, 20% with tetralogy of Fallot (n = 20), and 16% with previous Rastelli repair (n = 16). Overall, 37 EP studies were performed, with the majority done in patients with complex CHD. There were 74 additional cases. These procedures consisted of: 38 pacemakers (51%), 26 implantable cardiac defibrillators (36%), six laser lead extractions (8%), two loop recorders (3%), and two pocket revisions (3%). During this 5-year period, there was one major complication (1%) and seven minor complications (7%). CONCLUSIONS The complex care of adults with CHD requiring EP procedures can be safely and effectively accomplished in a freestanding pediatric hospital with low complications, provided institutional support of an adult CHD program.

Circulatory support using the impella device in fontan patients with systemic ventricular dysfunction: A multicenter experience

There are limited mechanical circulatory support options for patients with single ventricle (SV) anatomy. This is a multicenter, retrospective study of the Impella pump to support the systemic ventricle in a cohort of SV patients with Fontan circulation.