Elizabeth D. Sherwin

Characterization of Myocardial Repolarization Reserve in Adolescent Females With Anorexia Nervosa

Background— Patients with anorexia nervosa exhibit abnormal myocardial repolarization and are susceptible to sudden cardiac death. Exercise testing is useful in unmasking QT prolongation in disorders associated with abnormal repolarization. We characterized QT adaptation during exercise in anorexia. Methods and Results— Sixty-one adolescent female patients with anorexia nervosa and 45 age- and sex-matched healthy volunteers performed symptom-limited cycle ergometry during 12-lead ECG monitoring. Changes in the QT interval during exercise were measured, and QT/RR-interval slopes were determined by using mixed-effects regression modeling. Patients had significantly lower body mass index than controls; however, resting heart rates and QT/QTc intervals were similar at baseline. Patients had shorter exercise times (13.7±4.5 versus 20.6±4.5 minutes; P<0.001) and lower peak heart rates (159±20 versus 184±9 beats/min; P<0.001). The mean QTc intervals were longer at peak exercise in patients (442±29 versus 422±19 ms; P<0.001). During submaximal exertion at comparable heart rates (114±6 versus 115±11 beats/min; P=0.54), the QTc interval had prolonged significantly more in patients than controls (37±28 versus 24±25 ms; P<0.016). The RR/QT slope, best described by a curvilinear relationship, was more gradual in patients than in controls (13.4; 95% confidence interval, 12.8–13.9 versus 15.8; 95% confidence interval, 15.3–16.4 ms QT change per 10% change in RR interval; P<0.001) and steepest in patients within the highest body mass index tertile versus the lowest (13.9; 95% confidence interval, 12.9–14.9 versus 12.3; 95% confidence interval, 11.3–13.3; P=0.026). Conclusions— Despite the absence of manifest QT prolongation, adolescent anorexic females have impaired repolarization reserve in comparison with healthy controls. Further study may identify impaired QT dynamics as a risk factor for arrhythmias in anorexia nervosa.

Novel Variant in the ANK2 Membrane-Binding Domain Is Associated With Ankyrin-B Syndrome and Structural Heart Disease in a First Nations Population With a High Rate of Long QT Syndrome

Background— Long QT syndrome confers susceptibility to ventricular arrhythmia, predisposing to syncope, seizures, and sudden death. While rare globally, long QT syndrome is ≈15× more common in First Nations of Northern British Columbia largely because of a known mutation in KCNQ1. However, 2 large multigenerational families were affected, but negative for the known mutation. Methods and Results— Long QT syndrome panel testing was carried out in the index case of each family, and clinical information was collected. Cascade genotyping was performed. Biochemical and myocyte-based assays were performed to evaluate the identified gene variant for loss-of-function activity. Index cases in these 2 families harbored a novel ANK2 c.1937C>T variant (p.S646F). An additional 16 carriers were identified, including 2 with structural heart disease: one with cardiomyopathy resulting in sudden death and the other with congenital heart disease. For all carriers of this variant, the average QTc was 475 ms (±40). Although ankyrin-B p.S646F is appropriately folded and expressed in bacteria, the mutant polypeptide displays reduced expression in cultured H9c2 cells and aberrant localization in primary cardiomyocytes. Furthermore, myocytes expressing ankyrin-B p.S646F lack normal membrane targeting of the ankyrin-binding partner, the Na/Ca exchanger. Thus, ankyrin-B p.S646F is a loss-of-function variant. Conclusions— We identify the first disease-causing ANK2 variant localized to the membrane-binding domain resulting in reduced ankyrin-B expression and abnormal localization. Further study is warranted on the potential association of this variant with structural heart disease given the role of ANK2 in targeting and stabilization of key structural and signaling molecules in cardiac cells.

Transvenous nonfluoroscopic pacemaker implantation during pregnancy guided by 3-dimensional electroanatomic mapping

Introduction Patients with congenital heart disease are at ongoing risk of developing both bradyarrhythmias and tachyarrhythmias decades after surgical repair. Rarely, arrhythmias can be exacerbated during pregnancy and require emergent intervention. Here, we report unique experience with nonfluoroscopic pacemaker implantation during pregnancy. Ionizing radiation, even in low doses, is associated with an increased risk of malignancy, and a fetus may be at particularly increased risk. Over the past 2 decades, the use of fluoroscopy in cardiac ablation procedures has become nearly obsolete with the development of 3-dimensional (3D) electroanatomic mapping software such as CARTO (Biosense-Webster, Diamond Bar, CA) and NavX or EnSite (St. JudeMedical, Inc., St. Paul, MN). However, certain procedures, such as device implants, still commonly use fluoroscopy in most instances. Fluoroscopy use in patients with congenital heart disease is of utmost concern because of cumulative radiation exposure from multiple lifetime catheterization, radiographic and computed tomography imaging, and electrophysiological procedures.

Genetic Insurance Discrimination in Sudden Arrhythmia Death Syndromes: Empirical Evidence From a Cross-Sectional Survey in North America.

Background— There is virtually no information assessing the insurability of families affected with Sudden Arrhythmia Death Syndromes (SADS) for the determination of the nonclinical implications of genetic screening. It is important to identify the barriers and challenges faced by families as a result of genetic screening for SADS to enable equitable access to insurance coverage. Methods and Results— To explore the insurance coverage experiences of SADS-affected families, we administered a cross-sectional online survey across North America from April 28, 2012 to November 13, 2013. Participants included individuals with a SADS diagnosis and their relatives who have applied for insurance (health, life, travel, and disability) or have existing insurance coverage. Of 202 participants, 92% had a SADS diagnosis (92%) as either a proband (50%) or an affected relative (42%); 8% of participants were unaffected family members of a proband; and genetic confirmation was reported by 73%. Of the 54% of SADS respondents who applied for insurance, 60% were rejected by insurers. The preexisting SADS diagnosis was the major reason reported for rejection (57%). Most respondents (80%) had insurance coverage through a spouse/parent plan at the time of diagnosis; 14% experienced a subsequent negative effect on coverage. Thirty-nine percent of affected SADS respondents reported an increase in insurance premium rates. Conclusions— Increased genetic testing has negatively impacted insurability for SADS patients and affected family members. The challenges in obtaining life and health insurance are mainly because of the preexisting condition, even in the presence of protective laws in the United States.Background— There is virtually no information assessing the insurability of families affected with Sudden Arrhythmia Death Syndromes (SADS) for the determination of the nonclinical implications of genetic screening. It is important to identify the barriers and challenges faced by families as a result of genetic screening for SADS to enable equitable access to insurance coverage. Methods and Results— To explore the insurance coverage experiences of SADS-affected families, we administered a cross-sectional online survey across North America from April 28, 2012 to November 13, 2013. Participants included individuals with a SADS diagnosis and their relatives who have applied for insurance (health, life, travel, and disability) or have existing insurance coverage. Of 202 participants, 92% had a SADS diagnosis (92%) as either a proband (50%) or an affected relative (42%); 8% of participants were unaffected family members of a proband; and genetic confirmation was reported by 73%. Of the 54% of SADS respondents who applied for insurance, 60% were rejected by insurers. The preexisting SADS diagnosis was the major reason reported for rejection (57%). Most respondents (80%) had insurance coverage through a spouse/parent plan at the time of diagnosis; 14% experienced a subsequent negative effect on coverage. Thirty-nine percent of affected SADS respondents reported an increase in insurance premium rates. Conclusions— Increased genetic testing has negatively impacted insurability for SADS patients and affected family members. The challenges in obtaining life and health insurance are mainly because of the preexisting condition, even in the presence of protective laws in the United States.

Jellyfish-Like Accessory Mitral Valve Tissue Causing Near-Collapse in a Young Child.

Accessory mitral valve tissue (AMVT) causing left ventricular outflow tract obstruction (LVOTO) is rare. We report a case of AMVT causing severe LVOTO resulting in acutely progressive symptoms of near-collapse. Urgent surgical resection eliminated the patient’s life-threatening symptoms. AMVT should be considered among potential LVOTO diagnoses, and early surgical intervention may be required.

Genetic Insurance Discrimination in Sudden Arrhythmia Death SyndromesCLINICAL PERSPECTIVE

Background— There is virtually no information assessing the insurability of families affected with Sudden Arrhythmia Death Syndromes (SADS) for the determination of the nonclinical implications of genetic screening. It is important to identify the barriers and challenges faced by families as a result of genetic screening for SADS to enable equitable access to insurance coverage. Methods and Results— To explore the insurance coverage experiences of SADS-affected families, we administered a cross-sectional online survey across North America from April 28, 2012 to November 13, 2013. Participants included individuals with a SADS diagnosis and their relatives who have applied for insurance (health, life, travel, and disability) or have existing insurance coverage. Of 202 participants, 92% had a SADS diagnosis (92%) as either a proband (50%) or an affected relative (42%); 8% of participants were unaffected family members of a proband; and genetic confirmation was reported by 73%. Of the 54% of SADS respondents who applied for insurance, 60% were rejected by insurers. The preexisting SADS diagnosis was the major reason reported for rejection (57%). Most respondents (80%) had insurance coverage through a spouse/parent plan at the time of diagnosis; 14% experienced a subsequent negative effect on coverage. Thirty-nine percent of affected SADS respondents reported an increase in insurance premium rates. Conclusions— Increased genetic testing has negatively impacted insurability for SADS patients and affected family members. The challenges in obtaining life and health insurance are mainly because of the preexisting condition, even in the presence of protective laws in the United States.Background— There is virtually no information assessing the insurability of families affected with Sudden Arrhythmia Death Syndromes (SADS) for the determination of the nonclinical implications of genetic screening. It is important to identify the barriers and challenges faced by families as a result of genetic screening for SADS to enable equitable access to insurance coverage. Methods and Results— To explore the insurance coverage experiences of SADS-affected families, we administered a cross-sectional online survey across North America from April 28, 2012 to November 13, 2013. Participants included individuals with a SADS diagnosis and their relatives who have applied for insurance (health, life, travel, and disability) or have existing insurance coverage. Of 202 participants, 92% had a SADS diagnosis (92%) as either a proband (50%) or an affected relative (42%); 8% of participants were unaffected family members of a proband; and genetic confirmation was reported by 73%. Of the 54% of SADS respondents who applied for insurance, 60% were rejected by insurers. The preexisting SADS diagnosis was the major reason reported for rejection (57%). Most respondents (80%) had insurance coverage through a spouse/parent plan at the time of diagnosis; 14% experienced a subsequent negative effect on coverage. Thirty-nine percent of affected SADS respondents reported an increase in insurance premium rates. Conclusions— Increased genetic testing has negatively impacted insurability for SADS patients and affected family members. The challenges in obtaining life and health insurance are mainly because of the preexisting condition, even in the presence of protective laws in the United States.

Genetic Insurance Discrimination in Sudden Arrhythmia Death SyndromesCLINICAL PERSPECTIVE: Empirical Evidence From a Cross-Sectional Survey in North America

Background— There is virtually no information assessing the insurability of families affected with Sudden Arrhythmia Death Syndromes (SADS) for the determination of the nonclinical implications of genetic screening. It is important to identify the barriers and challenges faced by families as a result of genetic screening for SADS to enable equitable access to insurance coverage. Methods and Results— To explore the insurance coverage experiences of SADS-affected families, we administered a cross-sectional online survey across North America from April 28, 2012 to November 13, 2013. Participants included individuals with a SADS diagnosis and their relatives who have applied for insurance (health, life, travel, and disability) or have existing insurance coverage. Of 202 participants, 92% had a SADS diagnosis (92%) as either a proband (50%) or an affected relative (42%); 8% of participants were unaffected family members of a proband; and genetic confirmation was reported by 73%. Of the 54% of SADS respondents who applied for insurance, 60% were rejected by insurers. The preexisting SADS diagnosis was the major reason reported for rejection (57%). Most respondents (80%) had insurance coverage through a spouse/parent plan at the time of diagnosis; 14% experienced a subsequent negative effect on coverage. Thirty-nine percent of affected SADS respondents reported an increase in insurance premium rates. Conclusions— Increased genetic testing has negatively impacted insurability for SADS patients and affected family members. The challenges in obtaining life and health insurance are mainly because of the preexisting condition, even in the presence of protective laws in the United States.Background— There is virtually no information assessing the insurability of families affected with Sudden Arrhythmia Death Syndromes (SADS) for the determination of the nonclinical implications of genetic screening. It is important to identify the barriers and challenges faced by families as a result of genetic screening for SADS to enable equitable access to insurance coverage. Methods and Results— To explore the insurance coverage experiences of SADS-affected families, we administered a cross-sectional online survey across North America from April 28, 2012 to November 13, 2013. Participants included individuals with a SADS diagnosis and their relatives who have applied for insurance (health, life, travel, and disability) or have existing insurance coverage. Of 202 participants, 92% had a SADS diagnosis (92%) as either a proband (50%) or an affected relative (42%); 8% of participants were unaffected family members of a proband; and genetic confirmation was reported by 73%. Of the 54% of SADS respondents who applied for insurance, 60% were rejected by insurers. The preexisting SADS diagnosis was the major reason reported for rejection (57%). Most respondents (80%) had insurance coverage through a spouse/parent plan at the time of diagnosis; 14% experienced a subsequent negative effect on coverage. Thirty-nine percent of affected SADS respondents reported an increase in insurance premium rates. Conclusions— Increased genetic testing has negatively impacted insurability for SADS patients and affected family members. The challenges in obtaining life and health insurance are mainly because of the preexisting condition, even in the presence of protective laws in the United States.

Where to Throw That Shoe? Catheter Ablation of Atrioventricular Nodal Reentrant Tachycardia in Congenital Heart Disease.

Atrioventricular (AV) nodal reentrant tachycardia (AVNRT) is one of the most common arrhythmias presenting during childhood. It is typically thought of as more of a nuisance problem rather than a life-threatening condition. Catheter ablation of the slow AV nodal pathway is almost always curative with a low complication rate. Unlike accessory pathways, in which a precise and complete ablation is required, elimination of AVNRT can often be achieved by a less-than-lethal modification of the substrate. This is actually pretty amazing, considering that despite over 30 years of catheter ablation therapy for AVNRT, we still have limited understanding of the actual anatomy and physiology of the AV node and its slow and fast AV nodal pathways. Yet, catheter ablation is highly successful with low risk of complications in most patients. We have made remarkable progress over those decades, transitioning from open surgical ablation approaches to transvenous catheter-based ablation, first with direct current shocks, followed by less dramatic and traumatic energy sources—mainly radiofrequency and freezing.1–3 As with most new techniques, they are typically first trialed in adults, but radiofrequency catheter ablation for AVNRT was promptly used in children, with encouraging initial success.4 Many thousands of pediatric AVNRT patients later, catheter ablation is now a routine outpatient procedure with excellent long-term results.5–7 However, in the presence of structural congenital heart disease (CHD), …

Sudden Cardiac Death in Children and Adolescents

Sudden cardiac death (SCD) is a rare but devastating event in children and adolescents. Etiologies include congenital heart disease, cardiomyopathies, primary arrhythmia syndromes, and miscellaneous conditions. Challenges in the diagnosis and prevention of SCD in the young are reviewed.

Choking-induced cardiac arrest unmasks a diagnosis of catecholaminergic polymorphic ventricular tachycardia

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an uncommon cardiac ion channelopathy characterized by polymorphic or bidirectional ventricular tachycardia (VT) during physical or emotional stress. The proband often presents during childhood or early adolescence with syncope, seizure, or cardiac arrest. In some cases, sudden unexpected death (SUD) can be the first manifestation of CPVT. In 2001, Priori et al discovered that mutations in the cardiac ryanodine receptor 2 (RyR2), a highly conserved ion channel, underlie most cases of CPVT. The diagnosis is made on the basis of history, exercise stress testing (EST), and genetic testing. The management of CPVT is challenging. Classically, beta blockers are used to suppress arrhythmia, although nonadherence and treatment failure commonly occur. Flecainide is a promising second-line agent in CPVT. Patients with refractory arrhythmia or aborted cardiac arrest may be referred for an implantable cardioverter-defibrillator (ICD). Recently, a multicenter study showed benefit from left cardiac sympathetic denervation (LCSD). The presented case describes a very young child with a unique trigger for cardiac arrest in CPVT.