Paul Stephens

Anomalous Aortic Origin of a Coronary Artery With an Interarterial Course: Should Family Screening Be Routine?

OBJECTIVES We sought to present cases of familial occurrence of anomalous aortic origin of a coronary artery with an interarterial course (AAOCA) to determine if it would alter our current screening and management recommendations. BACKGROUND Anomalous aortic origin of a coronary artery with an interarterial course is a rare congenital anomaly that carries an increased risk of sudden death in children and young adults. There are no reports in the literature of familial AAOCA in the pediatric population. METHODS In preparation for a multi-institutional prospective study evaluating patient management and surgical outcomes in children and young adults with AAOCA, a questionnaire was sent to multiple pediatric institutions in North and South America. Several respondents indicated caring for families with more than 1 member with AAOCA. These patients were identified and charts were retrospectively reviewed. RESULTS We identified 5 families in which a child was diagnosed with AAOCA and another family member was subsequently identified through screening with echocardiography. The odds of this occurring are significantly greater than what would be expected by chance. All identified by screening were asymptomatic and had anomalous right coronary artery despite 2 of the 5 index cases having anomalous left coronary artery. CONCLUSIONS It is possible that there is a genetic link for AAOCA. Future research into this is warranted. Due to the potential risk of myocardial ischemia and sudden death associated with AAOCA, screening first-degree relatives for AAOCA using transthoracic echocardiography would be the prudent approach to potentially prevent a sudden catastrophic event.

Identification, imaging, functional assessment and management of congenital coronary arterial abnormalities in children

The coronary arteries, the vessels through which both substrate and oxygen are provided to the cardiac muscle, normally arise from paired stems, right and left, each arising from a separate and distinct sinus of the aortic valve. The right coronary artery runs through the right atrioventricular groove, terminating in the majority of instances in the inferior interventricular groove. The main stem of the left coronary artery bifurcates into the anterior descending, or interventricular, and the circumflex branches. Origin of the anterior descending and circumflex arteries from separate orifices from the left sinus of Valsalva occurs in about 1% of the population, while it is also frequent to find the infundibular artery arising as a separate branch from the right sinus of Valsalva. Anomalies of the coronary arteries can result from rudimentary persistence of an embryologic coronary arterial structure, failure of normal development or normal atrophy as part of development, or misplacement of connection of a an otherwise normal coronary artery. Anomalies, therefore, can be summarized in terms of abnormal origin or course, abnormal number of coronary arteries, lack of patency of the orifice of coronary artery, or abnormal connections of the arteries. Anomalous origin of the left coronary artery from the pulmonary trunk occurs with an incidence of approximately 1 in 300,000 children. The degree of left ventricular dysfunction produced likely relates to the development of collateral vessels that arise from the right coronary artery, and provide flow into the left system. Anomalous origin of either the right or the left coronary artery from the opposite sinus of Valsalva can be relatively innocuous, but if the anomalous artery takes an interarterial course between the pulmonary trunk and the aorta, this can underlie sudden death, almost invariably during or immediately following strenuous exercise or competitive sporting events. Distal anomalies of the coronary arteries most commonly involve abnormal connections, or fistulas, between the right or left coronary arterial systems and a chamber or vessel. We discuss the current techniques available for imaging these various lesions, along with their functional assessment, concluding with a summary of current strategies for management.

Serum alkaline phosphatase reflects post-Fontan hemodynamics in children.

Although survivors of Fontan palliation for a single ventricle are known to have lower cardiac index than patients with two-ventricle surgical reconstructions, it is unclear whether two frequently observed sequelae, short stature and protein-losing enteropathy (PLE), have hemodynamic origins. A serum marker that reflects hemodynamic status would be a tremendous asset in the long-term management of children with these sequelae. The authors recently noted severely reduced total alkaline phosphatase (TALP) levels in two children with early-onset PLE after Fontan operations, both of whom had low cardiac output at cardiac catheterization. Catheter-based or surgical interventions that rapidly increased cardiac output in these two patients resulted not only in relief of PLE but also in a prompt TALP rise. To examine whether the apparent correlation of low TALP with impaired cardiac output also is seen in Fontan patients without PLE, this study retrospectively examined the TALP data from two other Fontan patients who underwent cardiac catheterization specifically to assess the potential benefit of vasodilator therapy. The TALP levels were abnormally low in both cases but increased after uptitration of angiotensin-converting enzyme inhibition. Serum TALP activity, an indicator of osteoblastic function particularly in preadolescence, may be a marker of low cardiac output after a Fontan operation.

Effects of β-Adrenergic Antagonists on the QT Measurements from Exercise Stress Tests in Pediatric Patients with Long QT Syndrome

It has been proposed that β-adrenergic antagonist protection against cardiac events in patients with long QT syndrome (LQTS) may be related to a decrease in baseline QTc dispersion. To determine the effects of β-blocker therapy on QT measurements, we evaluated the exercise tests of 25 pediatric patients with LQTS. Measurements were made of the maximum QTc interval and QTc dispersion during the various segments of the exercise test. There was no statistically significant difference between the pre-β-blocker and post-β-blocker maximum QTc interval during the supine (0.473 ± 0.039 vs 0.470 ± 0.038 sec), exercise (0.488 ± 0.044 vs 0.500 ± 0.026 sec), or recovery (0.490 ± 0.031 vs 0.493 ± 0.029 sec) phases of the exercise stress test. There was also no statistically significant difference between the pre-β-blocker and post-β-blocker QTc dispersion during the supine (0.047 ± 0.021 vs 0.058 ± 0.033 sec), exercise (0.063 ± 0.036 vs 0.063 ± 0.028 sec), or recovery (0.045 ± 0.023 vs 0.052 ± 0.026 sec) phases of the exercise stress test. Therefore, the protection that β-blockers offer appears not to be related to a reduction of the baseline QTc interval or a decrease of QTc dispersion.

Ventricular tachycardia in infants with structurally normal heart: a benign disorder

We evaluated the presentation, treatment, and outcome of infants who present with ventricular tachycardia in the first year of life. Seventy-six infants were admitted to our institution with a diagnosis of ventricular tachycardia between January, 1987 and May, 2006. Forty-five infants were excluded from the study because of additional confounding diagnoses including accelerated idioventricular rhythm, Wolff-Parkinson-White syndrome, supraventricular tachycardia with aberrancy, long QT syndrome, cardiac rhabdomyoma, myocarditis, congenital lesions, or incomplete data. The remaining 31 included infants who had a median age at presentation of 1 day, with a range from 1 to 255 days, and a mean ventricular tachycardia rate of 213 beats per minute, with a range from 171 to 280, at presentation. The infants were treated chronically with propranolol (38.7%), amiodarone (12.9%), mexiletine (3.2%), propranolol and mexiletine (9.7%), or propranolol and procainamide (6.5%). The median duration of treatment was 13 months, with a range from 3 to 105 months. Ventricular tachycardia resolved spontaneously in all infants. No patient died, or received catheter ablation or device therapy. Median age at last ventricular tachycardia was 59 days, with a range from 1 to 836 days. Mean follow-up was 45 months, with a range from 5 to 164 months, with a mean ventricular tachycardia-free period of 40 months. Infants with asymptomatic ventricular tachycardia, a structurally normal heart, and no additional electrophysiological diagnosis all had spontaneous resolution of tachycardia. Furthermore, log-rank analysis of the time to ventricular tachycardia resolution showed no difference between children who received chronic outpatient anti-arrhythmic treatment and those who had no such therapy. While indications for therapy cannot be determined from this study, lack of symptoms or myocardial dysfunction suggests that therapy may not be necessary.

Noninvasive imaging of isolated persistent fifth aortic arch.

Persistent fifth aortic arch was suspected by echocardiography and confirmed by magnetic resonance imaging (MRI) in an infant with a heart murmur. Selected images including three dimensional reconstruction from MRI demonstrating this very rare congenital anomaly are presented.

A family with a complex clinical presentation characterized by arrhythmogenic right ventricular dysplasia/cardiomyopathy and features of branchio-oculo-facial syndrome.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a familial form of cardiomyopathy typically caused by mutations in genes that encode an element of the cardiac desmosome. Branchio‐oculo‐facial syndrome (BOFS) is a craniofacial disorder caused by TFAP2A mutations. In a family segregating ARVD/C, some members also had features of BOFS. Genetic testing for ARVD/C identified a mutation in PKP2, encoding plakophilin‐2, a component of the cardiac desmosome. Evaluation of dysmorphology by chromosome microarray (CMA) identified a 4.4 Mb deletion at chromosome 6p24 that included both TFAP2A and DSP, encoding desmoplakin, an additional component of the cardiac desmosome implicated in ARVD/C. A family member with both the 6p24 deletion and PKP2 mutation had more severe cardiac dysfunction. These findings suggest that this contiguous gene deletion contributes to both ARVD/C and BOFS, and that DSP haploinsufficiency may contribute to cardiomyopathy. This family provides a clinical example that underscores the need for careful evaluation in clinical scenarios where genetic heterogeneity is known to exist. Finally, it suggests that individuals with unexplained cardiomyopathy and dysmorphic facial features may benefit from CMA analysis.

Postoperative Obstruction of the Pulmonary Veins in Mixed Total Anomalous Pulmonary Venous Connection

Total anomalous pulmonary venous connection (TAPVC) is a rare form of congenital heart disease in which the pulmonary veins drain by various pathways to the right atrium instead of the left atrium. Postoperative obstruction of the pulmonary veins is a known complication. Identifying risk factors for morbidity and mortality is important for counseling and monitoring. We describe a pattern of postoperative obstruction in a specific arrangement of mixed TAPVC. Five patients with a type of mixed TAPVC, namely, three pulmonary veins connecting to the coronary sinus and the left upper pulmonary vein (LUPV) connecting to the innominate vein, were identified over an 11-year period at our institution. Two additional patients with this TAPVC arrangement were cared for at our institution after having surgery at other institutions. Of these, one patient received only comfort care at birth due to other clinical issues. The six other patients underwent surgical unroofing of the coronary sinus. The anomalous LUPV was not addressed during the initial surgery in any of these cases. Following repair, one patient died from non-cardiac reasons. The remaining five patients all developed obstruction of the repaired pulmonary veins with decompression through the unrepaired LUPV, requiring surgical revision. Three patients underwent a second reoperation as well. Three of the six repaired patients also developed refractory atrial arrhythmias. This cohort suggests that this mixed TAPVC pattern predisposes patients to obstruction after surgical repair. Further investigation may aid pediatric cardiologists in risk-stratifying and counseling these patients. Alternative surgical approaches may need to be considered.

Sudden cardiac death in the young: the value of exercise testing.

Paediatric exercise stress testing has historically been used to assess the functional status of patients after repair of CHDs and to assess the efficacy of medical or device therapy in patients with arrhythmias. Exercise stress testing is one of very few hospital- or clinic-based tests that can assess the response of the cardiopulmonary system in an environment that simulates the bodys response to vigorous play and competitive sport. Exercise stress testing is therefore a useful modality in the assessment of child and athletes at risk for sudden cardiac death. The author discusses some cardiovascular maladies that can cause sudden cardiac death by utilising case illustrations as a learning tool.

Abnormalities in serum biomarkers correlate with lower cardiac index in the Fontan population

BACKGROUND Fontan survivors have depressed cardiac index that worsens over time. Serum biomarker measurement is minimally invasive, rapid, widely available, and may be useful for serial monitoring. The purpose of this study was to identify biomarkers that correlate with lower cardiac index in Fontan patients. Methods and results This study was a multi-centre case series assessing the correlations between biomarkers and cardiac magnetic resonance-derived cardiac index in Fontan patients ⩾6 years of age with biochemical and haematopoietic biomarkers obtained ±12 months from cardiac magnetic resonance. Medical history and biomarker values were obtained by chart review. Spearmans Rank correlation assessed associations between biomarker z-scores and cardiac index. Biomarkers with significant correlations had receiver operating characteristic curves and area under the curve estimated. In total, 97 cardiac magnetic resonances in 87 patients met inclusion criteria: median age at cardiac magnetic resonance was 15 (6-33) years. Significant correlations were found between cardiac index and total alkaline phosphatase (-0.26, p=0.04), estimated creatinine clearance (0.26, p=0.02), and mean corpuscular volume (-0.32, p<0.01). Area under the curve for the three individual biomarkers was 0.63-0.69. Area under the curve for the three-biomarker panel was 0.75. Comparison of cardiac index above and below the receiver operating characteristic curve-identified cut-off points revealed significant differences for each biomarker (p<0.01) and for the composite panel [median cardiac index for higher-risk group=2.17 L/minute/m2 versus lower-risk group=2.96 L/minute/m2, (p<0.01)]. CONCLUSIONS Higher total alkaline phosphatase and mean corpuscular volume as well as lower estimated creatinine clearance identify Fontan patients with lower cardiac index. Using biomarkers to monitor haemodynamics and organ-specific effects warrants prospective investigation.