Jane E. Crosson

Recommendations for Physical Activity and Recreational Sports Participation for Young Patients With Genetic Cardiovascular Diseases

A group of relatively uncommon but important genetic cardiovascular diseases (GCVDs) are associated with increased risk for sudden cardiac death during exercise, including hypertrophic cardiomyopathy, long-QT syndrome, Marfan syndrome, and arrhythmogenic right ventricular cardiomyopathy. These conditions, characterized by diverse phenotypic expression and genetic substrates, account for a substantial proportion of unexpected and usually arrhythmia-based fatal events during adolescence and young adulthood. Guidelines are in place governing eligibility and disqualification criteria for competitive athletes with these GCVDs (eg, Bethesda Conference No. 26 and its update as Bethesda Conference No. 36 in 2005). However, similar systematic recommendations for the much larger population of patients with GCVD who are not trained athletes, but nevertheless wish to participate in any of a variety of recreational physical activities and sports, have not been available. The practicing clinician is frequently confronted with the dilemma of designing noncompetitive exercise programs for athletes with GCVD after disqualification from competition, as well as for those patients with such conditions who do not aspire to organized sports. Indeed, many asymptomatic (or mildly symptomatic) patients with GCVD desire a physically active lifestyle with participation in recreational and leisure-time activities to take advantage of the many documented benefits of exercise. However, to date, no reference document has been available for ascertaining which types of physical activity could be regarded as either prudent or inadvisable in these subgroups of patients. Therefore, given this clear and present need, this American Heart Association consensus document was constituted, based largely on the experience and insights of the expert panel, to offer recommendations governing recreational exercise for patients with known GCVDs.

Dilated cardiomyopathy in isolated congenital complete atrioventricular block: early and long-term risk in children

OBJECTIVES We sought to identify the risk factors predicting the development of dilated cardiomyopathy (DCM) in patients with isolated congenital complete atrioventricular block (CCAVB). BACKGROUND Recently evidence has emerged that a subset of patients with CCAVB develop DCM. METHODS This was a retrospective study of 149 patients with CCAVB who had heart size and left ventricular (LV) function assessed by echocardiography and chest radiography over a follow-up period of 10 +/- 7 years. RESULTS Nine patients developed DCM at the age of 6.5 +/- 5 years. No definite cause could be identified. In these nine patients, CCAVB was diagnosed in eight at 23 +/- 2.3 weeks gestation and in one at birth. Maternal SSA/SSB antibodies were confirmed in seven of the nine patients. Pacemakers were implanted in eight patients in the first month and in one patient at five years of age. The initial left ventricular end-diastolic dimension (LVEDD) was in the 96th +/- 2.6 percentile and the cardiothoracic (CT) ratio was 64 +/- 3.8% in the nine patients who developed DCM, and differed significantly in patients with CCAVB (p < 0.005) who did not develop DCM. The LVEDD and CT ratio did not decrease in the patients with CCAVB and DCM, but decreased significantly in the patients with CCAVB without DCM (p < 0.001) once pacing was initiated. Two patients with DCM died within two months of diagnosis; one patient is neurologically compromised; two patients received a heart transplant; and four patients are listed for heart transplantation. CONCLUSIONS Isolated CCAVB is associated with a long-term risk for the development of DCM. Risk factors may be SSA/SSB antibodies, increased heart size at initial evaluation and the absence of pacemaker-associated improvement.

Lead Configuration for Defibrillator Implantation in a Patient with Congenital Heart Disease and a Mechanical Prosthetic Tricuspid Valve

LENG, C.T., et al.: Lead Configuration for Defibrillator Implantation in a Patient with Congenital Heart Disease and a Mechanical Prosthetic Tricuspid Valve. The authors devised a nonthoracotomy defibrillation system for a patient with a prosthetic tricuspid valve using existing technology and previously established implantation techniques. Their lead configuration deviates substantially from existing designs in its primary use of a coronary sinus defibrillation coil and a left‐sided subcutaneous array to distribute current across the ventricular myocardium.

Infantile Restrictive Cardiomyopathy Resulting From a Mutation in the Cardiac Troponin T Gene

Here we report the first infantile case of restrictive cardiomyopathy caused by a de novo mutation of the cardiac troponin T gene. The patient presented with an apparent life-threatening event. She developed malignant arrhythmias and hemodynamic instability, requiring initial rescue support with extracorporeal membrane oxygenation, and subsequently underwent insertion of a biventricular assist device (VAD). She successfully received an orthotopic heart transplant 172 days after VAD implantation.

Endocardial and epicardial steroid lead pacing in the neonatal and paediatric age group

Aim: To compare the performance of steroid eluting epicardial and endocardial leads in infants and children requiring permanent pacing. Methods: Evaluation of pacing and sensing characteristics, impedances, and longevity of 159 steroid eluting leads implanted in 95 children. Group A consisted of 24 children weighing less than 15 kg with 15 endocardial leads (five atrial, 10 ventricular) and 19 epicardial leads (five atrial, 14 ventricular). Group B consisted of 71 children weighing more than 15 kg with 106 endocardial leads (56 atrial, 58 ventricular) and 19 epicardial leads (nine atrial, 10 ventricular). Results: Group A: Stimulation thresholds were lower for ventricular endocardial leads at implant (mean (SD) 0.84 (0.54) v 1.59 (0.64) V, p < 0.014) and at two year follow up (ventricular 0.64 (0.24) v 1.65 (0.69) V, p < 0.003). Impedance and sensing thresholds did not differ significantly at implant and follow up. Group B: Stimulation thresholds were lower for ventricular endocardial leads at implant (0.72 (0.48) v 1.48 (0.58) V, p < 0.001) and at follow up (0.88 (0.46) v 1.55 (0.96) V, p < 0.009). Impedance did not differ. Sensing thresholds were also better for ventricular endocardial leads at follow up (9.1 (5.2) v 14.2 (6.4) mV, p < 0.02). Complications requiring intervention occurred in both groups (n = 7 for endocardial v n = 18 for epicardial leads). Conclusions: Endocardial and epicardial steroid eluting leads have comparable performance in the paediatric population.

The Relevance of Prolonged QTc Measurement to Pediatric Psychopharmacology

OBJECTIVE To consider the relevance of prolonged QTc (QT interval corrected for rate) to pediatric psychopharmacology. METHOD The authors reviewed publications on QTc prolongation and publications on sudden death in Medline from 1968 to November 2002. RESULTS The search yielded more than 20,000 publications. Review manuscripts with clinical recommendations outnumber the few pediatric studies of QTc duration during treatment. Most reviews have been published in the past 5 years, during a time when the Food and Drug Administration restricted five psychotropic medications because of QTc prolongation (sertindole: not approved; thioridazine, mesoridazine, and droperidol: black-box warning; and ziprasidone: bolded warning) and nine somatic medications because of QTc prolongation. CONCLUSION Pretreatment screening, careful selection of psychotropic and/or somatic medication combinations, and recognition of QTc prolongation in electrocardiographic tracings during treatment with medications that prolong QTc are important components of clinical practice.

Pacemaker therapy in isolated congenital complete atrioventricular block.

BREUR, J.M.P.J., et al.: Pacemaker Therapy in Isolated Congenital Complete Atrioventricular Block. The aim of this study was to evaluate the effect of pacemaker (PM) therapy in patients with isolated congenital complete atrioventricular block (CCAVB). Patients with CCAVB eventually qualify for PM implantation, however, timing remains controversial. Retrospective evaluation of left ventricular end‐diastolic diameter (LVEDD), shortening fraction (SF), and cardiothoracic ratio (CTR) in 149 CCAVB patients, before, at, and after PM implantation was carried out. LVEDD shows an average increase of 0.48%/month in non‐PM patients, and an average decrease of 0.88%/month in PM patients. SF shows an average increase of 0.10%/month in non‐PM, and an average decrease of 0.32%/month in PM patients. CTR shows an average increase of 0.02%/month in non‐PM, and an average decrease of 0.19%/month in PM patients. The difference between the non‐PM and PM groups is significant (P = 0.05) for all variables. Symptomatic patients show no significant change in LVEDD after PM therapy (from 66.5% before to 68.5% after PM therapy). Asymptomatic patients do show a significant (P < 0.001) decrease in LVEDD after PM therapy (from 78.4% before to 73.3% after PM therapy). CTR does not differ significantly between symptomatic and asymptomatic patients before PM therapy (58% and 57%, respectively). CTR does differ significantly (P < 0.001) between symptomatic and asymptomatic patients after PM therapy (52% and 48%, respectively). Heart size and SF are increased in most patients with isolated CCAVB. PM implantation is associated with a decrease in heart size and normalization of SF in most patients. Indications for PM therapy in children may require reevaluation in asymptomatic patients with increased cardiac size and decreased cardiac function.

Mutations in Alström protein impair terminal differentiation of cardiomyocytes

Cardiomyocyte cell division and replication in mammals proceed through embryonic development and abruptly decline soon after birth. The process governing cardiomyocyte cell cycle arrest is poorly understood. Here we carry out whole exome sequencing in an infant with evidence of persistent postnatal cardiomyocyte replication to determine the genetic risk factors. We identify compound heterozygous ALMS1 mutations in the proband, and confirm their presence in her affected sibling, one copy inherited from each heterozygous parent. Next, we recognise homozygous or compound heterozygous truncating mutations in ALMS1 in four other children with high levels of postnatal cardiomyocyte proliferation. Alms1 mRNA knockdown increases multiple markers of proliferation in cardiomyocytes, the percentage of cardiomyocytes in G2/M phases, and the number of cardiomyocytes by 10% in cultured cells. Homozygous Alms1-mutant mice have increased cardiomyocyte proliferation at two weeks postnatal compared to wild-type littermates. We conclude that deficiency of Alström protein impairs postnatal cardiomyocyte cell cycle arrest.

PACES/HRS Expert Consensus Statement on the Evaluation and Management of Ventricular Arrhythmias in the Child With a Structurally Normal Heart

and Management of Ventricular Arrhythmias in the Child With a Structurally Normal Heart Jane E. Crosson, MD, FACC (Chair), David J. Callans, MD, FHRS, FACC, FAHA (Chair), David J. Bradley, MD, FACC, FAAP, Anne Dubin, MD, FHRS, FAHA, FACC, Michael Epstein, MD, FACC, CCDC, Susan Etheridge, MD, FHRS, FACC, FAAP, CEPS, Andrew Papez, MD, FHRS, CCDS, John R. Phillips, MD, FAAP, FHRS, FACC, Larry A. Rhodes, MD, FAAP, FHRS, FACC, Philip Saul, MD, FHRS, FACC, FAHA, Elizabeth Stephenson, MD, MSc, FHRS, CCDS, CEPS, William Stevenson, MD, FAHA, FHRS, FACC, Frank Zimmerman, MD, FAHA, FHRS From the Bloomberg Children’s Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, C.S. Mott Children’s Hospital, Anne Arbor, Michigan, Lucile Packard Children’s Hospital, Stanford School of Medicine, Stanford, California, Maine Medical Center, Portland, Maine, University of Utah and Primary Children’s Medical Center, Salt Lake City, Utah, Phoenix Children’s Hospital/Arizona Pediatric Cardiology Consultants Phoenix, Arizona, WVUH Children’s Hospital, Morgantown, West Virginia, Nationwide Children’s Hospital, Ohio State University, Columbus, Ohio, University of Toronto, Toronto, Ontario, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, and Advocate Heart Institute for Children Advocate Children’s Hospital, Oak Lawn, Illinois.

Placement of implantable cardioverter‐defibrillators in paediatric and congenital heart defect patients: a pipeline for model generation and simulation prediction of optimal configurations

•  Implantable cardioverter‐defibrillators (ICDs) with transvenous leads often cannot be implanted in a standard manner in paediatric and congenital heart defect (CHD) patients. Currently, there is no reliable approach to predict the optimal ICD placement in these patients. •  A pipeline for constructing personalized, electrophysiological heart–torso models from clinical magnetic resonance imaging scans was developed and applied to a paediatric CHD patient. •  Optimal ICD placement was determined using patient‐specific simulations of the defibrillation process. In a patient with tricuspid valve atresia, two configurations with epicardial leads were found to have the lowest defibrillation threshold. •  We demonstrated that determining extracellular potential (Φe) gradients during the shock – without actually simulating defibrillation – was not sufficient to predict defibrillation success or failure. •  Using the proposed methodology, the optimal ICD placement in paediatric/CHD patients can be predicted computationally, which could reduce defibrillation energy if the pipeline is used as part of ICD implantation planning.