Effect of long-term right ventricular pacing in young adults with structurally normal heart.

BACKGROUND: Right ventricular pacing increases the risk of heart failure in adults with structural heart disease. The impact of prolonged right ventricular pacing in adults without structural heart disease is not fully characterized and may depend on interactions of pacing with abnormal substrate predisposing to ventricular dysfunction. METHODS AND RESULTS: We assessed the effect of right ventricular pacing in patients who underwent pacemaker implantation for isolated congenital atrioventricular block between 1964 and 2005. To assess for immunologic contribution to cardiac dysfunction, outcomes were compared between patients with (Ab(+)) and without (Ab(-)) antinuclear antibody during adulthood and an age- and sex-matched Olmsted County, Minnesota, population. Of 103 patients (mean+/-SD age, 32+/-19 years), 18 were Ab(+). Long-term survival free of new heart failure after pacemaker implantation in isolated congenital atrioventricular block patients was worse than in the matched population (P<0.001). This difference was attributable to the development of heart failure in 12 Ab(+) patients (67%; P<0.001), without differences between Ab(-) patients (2%) and the matched population (2%; P=0.7). Compared with baseline, at last follow-up, left ventricular ejection fraction did not decline in Ab(-) (53+/-9% to 57+/-12%) but decreased in Ab(+)(52+/-10% to 38+/-12%; P=0.03) patients. Survival was similar in Ab(-) patients and the Minnesota population (98%; P=0.7) but worse in Ab(+) patients (79%; P<0.01). CONCLUSIONS: The natural history of patients with isolated congenital atrioventricular block who require pacing depends upon their antibody status. Antinuclear antibody status was a predictor for the development of heart failure and death. Long-term right ventricular pacing alone does not appear to be associated with development of heart failure, deterioration in ventricular function, or reduced survival in Ab(-) isolated congenital atrioventricular block patients.

Exercise performance in adolescents with autonomic dysfunction.

OBJECTIVE: To test the hypothesis that excessive postural tachycardia is associated with deconditioning rather than merely being an independent sign of autonomic dysfunction in patients with postural orthostatic tachycardia syndrome (POTS). STUDY DESIGN: We retrospectively analyzed records from 202 adolescents who underwent both head up-tilt and maximal exercise testing. Patients were classified as POTS if they had ≥ 30 min(-1) rise in heart rate (HR) after tilt-table test; and deconditioned if peak O(2) uptake was < 80% predicted. Changes in HR during exercise and recovery were compared between groups. RESULTS: Two-thirds of patients were deconditioned, irrespective of whether they fulfilled diagnostic criteria for POTS, but peak O(2) uptake among patients with POTS was similar to patients without POTS. HR was higher at rest and during exercise; whereas stroke volume was lower during exercise, and HR recovery was slower in patients with POTS compared with patients without POTS. CONCLUSIONS: Most patients who presented with chronic symptoms of dizziness, fatigue, or pre-syncope, were deconditioned, but, because the proportion of deconditioned patients was similar in POTS vs non-POTS groups, we conclude that HR changes in POTS are not solely because of inactivity resulting in deconditioning.

Outcomes in adolescents with postural orthostatic tachycardia syndrome treated with midodrine and beta-blockers.

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is associated with debilitating fatigue, dizziness, and discomfort in previously healthy adolescents. The effects of medical therapy have not been well studied in this patient population. This study assessed the relative efficacy and impact of drug therapy on the functioning and quality of life in adolescents with POTS. METHODS: A retrospective, single center, chart review analysis with a follow-up written survey was conducted on a group of 121 adolescents who had undergone autonomic reflex screening at the Mayo Clinic from 2002 to 2005 as part of an evaluation for possible POTS. RESULTS: Of 121 surveys sent, 47 adolescents returned a completed survey. In this cohort of patients, the two most commonly prescribed drug therapies were midodrine (n = 13) and beta-blockers (n = 14). Patients in the midodrine group were comparable to patients in the beta-blocker group in gender, age, pretreatment postural heart rate changes, and months from initial evaluation to survey completion. More patients treated with a beta-blocker reported improvement after visiting Mayo Clinic (100% vs 62%, P = 0.016) and more attributed their progress to medication (63.6% vs 36.4%, P = 0.011) than did those treated with midodrine. CONCLUSION: Treatment with both midodrine and beta-blockers was associated with overall improvement in POTS patients' general health; however, adolescents taking beta-blockers were more likely than those taking midodrine to credit the role of medications in their improvement.

Improvement in Functioning and Psychological Distress in Adolescents With Postural Orthostatic Tachycardia Syndrome Following Interdisciplinary Treatment.

Significant functional impairment and psychological distress have been observed in adolescent patients with postural orthostatic tachycardia syndrome (POTS). Interdisciplinary rehabilitation programs have been shown to be beneficial in the treatment of chronic pain in adults and adolescents. Only preliminary data have examined interdisciplinary rehabilitation efforts in patients with POTS. This study evaluated the impact of an interdisciplinary rehabilitation program on the functional impairment and psychological distress in 33 adolescents diagnosed with POTS. Patients included in the study were adolescents ages 11 to 18 diagnosed with POTS. Measures completed at admission and discharge from the program included the Functional Disability Index, Center for Epidemiological Studies-Depression-Child scale, and the Pain Catastrophizing Scale for Children. After participation in the 3-week program, adolescents with POTS demonstrated a significant increase in overall functional ability and significant reductions in depression and catastrophizing.

A trafficking defective, Brugada syndrome-causing SCN5A mutation rescued by drugs.

BACKGROUND: The human cardiac SCN5A gene encodes for the alpha subunit of the human cardiac voltage-dependent sodium channel hNav1.5 [Neuron 28 (2) (2000) 365] and carries inward Na current (INa). Mutations in SCN5A cause arrhythmia syndromes including Brugada syndrome (BrS) and congenital long QT syndrome subtype 3 (LQT3). Here, we report a trafficking defective BrS-causing SCN5A mutation that was drug-rescued. METHODS AND RESULTS: A 14-year-old Caucasian male was diagnosed with BrS with typical ECG pattern for BrS and ventricular fibrillation was easily induced. He also had significant HV interval delay ( approximately 65 ms) and high (31 J) defibrillation thresholds (DFTs). Genomic analysis revealed the SCN5A mutation (G1743R). We engineered G1743R into the cardiac Na channel and transfected HEK-293 cells for functional studies. The mutant channel yielded nearly undetectable sodium channel currents. Coexpression with the beta1 subunit, or incubation at low temperature did not increase current density. However, mexiletine, a sodium channel blocker, increased current density 93-fold in G1743R, but only twofold in WT. CONCLUSIONS: This study identifies an expression-defective BrS mutation in SCN5A with pharmacological rescue. The profoundly decreased sodium current associated with the G1743R suggests a molecular basis for the delayed His-Purkinje conduction and elevated DFTs observed in the proband. Whether the mutant channel may be rescued in vivo by mexiletine and normalize the patient's electrophysiologic parameters remains to be tested.

Role of transvenous implantable cardioverter-defibrillators in preventing sudden cardiac death in children, adolescents, and young adults.

OBJECTIVE: To evaluate the indications, underlying cardiac disorders, efficacy, and complications involved with transvenous implantable cardioverter-defibrillators (ICDs) in pediatric patients at the Mayo Clinic. PATIENTS AND METHODS: The records of all patients aged 21 years or younger who underwent transvenous ICD placement at the Mayo Clinic, Rochester, Minn, were reviewed retrospectively. RESULTS: Between March 1992 and September 2000, 16 patients (7 females; mean age, 15.4 years; range, 10-21 years) underwent transvenous ICD placement. The ICD was implanted for primary prevention of sudden cardiac death in 7 and for secondary prevention in 9. The underlying cardiac disorders included hypertrophic cardiomyopathy in 6 patients and congenital long QT syndrome in 6 patients. The mean +/- SD follow-up was 36+/-29 months (range, 5-108 months). There was no mortality. Seven patients (44%) received appropriate ICD therapy, including 6 of 9 who had ICDs placed for secondary prevention. Median time free from appropriate ICD discharge was 3 years (range, 0.2-9 years). Three patients (19%) experienced inappropriate ICD discharge. Two patients needed device replacement because of technical problems (lead fracture and device malfunction). Two patients developed pocket infection that required removal and reimplantation of the ICD. CONCLUSION: In adolescents and young adults, transvenous ICDs may prevent sudden death but are not free of complications. Forty-four percent of this cohort received potentially life-saving ICD therapy, including two thirds who received an ICD for secondary prevention.

Epinephrine-induced QT interval prolongation: a gene-specific paradoxical response in congenital long QT syndrome.

OBJECTIVE: To determine the effect of epinephrine on the QT interval in patients with genotyped long QT syndrome (LQTS). PATIENTS AND METHODS: Between May 1999 and April 2001, 37 patients (24 females) with genotyped LQTS (19 LQT1, 15 LQT2, 3 LQT3, mean age, 27 years; range, 10-53 years) from 21 different kindreds and 27 (16 females) controls (mean age, 31 years; range, 13-45 years) were studied at baseline and during gradually increasing doses of intravenous epinephrine infusion (0.05, 0.1, 0.2, and 0.3 microg x k(-1) x min(-1)). The 12-lead electrocardiogram was monitored continuously, and heart rate, QT, and corrected QT interval (QTc) were measured during each study stage. RESULTS: There was no significant difference in resting heart rate or chronotropic response to epinephrine between LQTS patients and controls. The mean +/- SD baseline QTc was greater in LQTS patients (500+/-68 ms) than in controls (436+/-19 ms, P<.001). However, 9 (47%) of 19 KVLQT1-genotyped LQT1 patients had a nondiagnostic resting QTc (<460 milliseconds), whereas 11 (41%) of 27 controls had a resting QTc higher than 440 milliseconds. During epinephrine infusion, every LQT1 patient manifested prolongation of the QT interval (paradoxical response), whereas healthy controls and patients with either LQT2 or LQT3 tended to have shortened QT intervals (P<.001). The maximum mean +/- SD change in QT (AQT [epinephrine QT minus baseline QT]) was -5+/-47 ms (controls), +94+/-31 ms (LQT1), and -87+/-67 ms (LQT2 and LQT3 patients). Of 27 controls, 6 had lengthening of their QT intervals (AQT >30 milliseconds) during high-dose epinephrine. Low-dose epinephrine (0.05 microg x kg(-1) x min(-1)) completely discriminated LQT1 patients (AQT, +82+/-34 ms) from controls (AQT, -7+/-13 ms; P<.001). Epinephrine-triggered nonsustained ventricular tachycardia occurred in 2 patients with LQTS and in 1 control. CONCLUSIONS: Epinephrine-induced prolongation of the QT interval appears pathognomonic for LQT1. Low-dose epinephrine infusion distinguishes controls from patients with concealed LQT1 manifesting an equivocal QTc at rest. Thus, epinephrine provocation may help unmask some patients with concealed LQTS and strategically direct molecular genetic testing.

Sudden cardiac death and channelopathies: a review of implantable defibrillator therapy.

This article focuses on implantable cardioverter-defibrillator (ICD) therapy in the child/adolescent who is predisposed to sudden cardiac death because of an underlying channelopathy. As such, the primary channelopathies are reviewed briefly. Next, the history of the ICD device and the technological advancements that have enabled its use in pediatrics are discussed. Finally, the clinical experience with ICDs in the young is summarized and general indications for device therapy in young patients who have a channelopathy are provided.

Surgical management of atrial tachyarrhythmias associated with congenital cardiac anomalies: Mayo Clinic experience.

Patients with congenital cardiac anomalies that cause right or left atrial dilatation may have associated atrial tachyarrhythmias, including atrial fibrillation and atrial flutter. Congenital cardiac anomalies may also be associated with Wolff-Parkinson-White syndrome or atrioventricular nodal re-entrant tachycardia. In addition, atrial arrhythmias may develop late after definitive operation for congenital cardiac anomalies, especially after the Fontan procedure. Ebstein's anomaly is the most common congenital cardiac anomaly associated with atrial arrhythmias. Atrial arrhythmias cause significant morbidity and mortality, as well as sudden death. Advances in electrophysiologic catheterization and surgical techniques have allowed the diagnosis, localization, and successful treatment of these arrhythmias.

Cardiac transplantation in a pediatric patient with systemic sclerosis.

INTRODUCTION: Diffuse cutaneous systemic sclerosis (SSc) is rare in children, but has a poor prognosis when cardiomyopathy is present. METHODS: We reviewed the case of a 14-year-old female with progressive skin thickening/tightness and dyspnea on exertion who was diagnosed with SSc. RESULTS: Our patient was found to have severe restrictive cardiomyopathy with poor left ventricular systolic function (ejection fraction = 20%), unresponsive to the immunosuppression used to treat her SSc. There was no evidence of pulmonary fibrosis. The patient underwent orthotopic cardiac transplantation, with improvement in systemic symptoms. Two years after transplantation, she had elevated filling pressures during a surveillance catheterization, with no evidence of cellular rejection or coronary artery vasculopathy. Four months later, she developed severe ventricular dysfunction and dyspnea, despite a negative biopsy and negative C4d immunofluorescence staining. Her immunosuppression was intensified with improvement of cardiac function. Despite this, 1 month later she had sudden pulseless cardiac arrest from which she could not be revived. The family declined an autopsy. DISCUSSION: We report a 14-year-old female with SSc who had cardiac transplantation. The etiology behind her recurrent restrictive physiology, cardiac dysfunction, and subsequent cardiac arrest remains unclear.

Characterization of atrial morphology and sinus node morphology in heterotaxy syndrome: an autopsy-based study of 41 cases (1950-2008).

BACKGROUND: Heterotaxy syndrome affects the sidedness of heart, lungs, and abdominal viscera, and is associated with complex congenital heart disease. Cardiac sidedness is defined by the position of the morphological right atrium and may be normal, mirror-image, or isomeric. The sinus node has been reported to be present bilaterally in right isomerism and absent bilaterally in left isomerism, although exceptions may occur. OBJECTIVE: Our aim was to evaluate bilaterally the presence or absence of sinus node tissue in autopsy-derived hearts from patients with heterotaxy and to correlate the findings with the sidedness of the two atria. METHODS: Autopsy and clinical records were reviewed from 41 cases with heterotaxy. From the cardiac specimens, tissue was collected bilaterally from expected sinus node sites. Sinus node tissue was categorized microscopically as normal, hypoplastic, indeterminate, or absent. RESULTS: In hearts thought to show right atrial isomerism, sinus node tissue was detected bilaterally in 54%, was absent on one side in 43%, and was absent on both sides in 3%. For cases with apparent left atrial isomerism, a single sinus node was present in the left-sided atrium in 75% of cases and was absent bilaterally in 25%. CONCLUSIONS: Bilateral sinus nodes were observed in only 54% of cases with right isomerism, and bilateral absence of sinus nodes was documented in only 25% of cases with left isomerism. Thus, our findings indicate that the sinus node is not a morphologically right-sided structure, and its presence therefore is not consistently related to the sidedness of the atria.

Isolated sympathetic failure with autoimmune autonomic ganglionopathy.

A 16-year-old boy had a gradual onset of post-exercise myalgia with progressive fatigue and dizziness. He had bradycardia (37 beats/minute) with low supine and normal standing norepinephrine levels (56 and 311 pg/mL, respectively). He had absent sympathetically mediated vasoconstrictor responses during Valsalva maneuver testing. Circulating ganglionic acetylcholine receptor antibodies were identified. Response was gradual to treatment with intravenous immunoglobulin combined with aggressive symptomatic interventions (permanent pacemaker implantation and treatment with pyridostigmine, midodrine, and modafinil). After the intravenous immunoglobulin treatment, his autoantibody levels decreased and the autonomic abnormalities resolved. After a reconditioning exercise program and eventually undetectable antibody titers, he achieved complete recovery. The patient continued to do well after his pacemaker was removed and his medications were discontinued. Thus, severe isolated sympathetic nervous system failure can occur in adolescents with autoimmune autonomic ganglionopathy, and multifaceted treatment can be effective.

Orthostatic heart rate and blood pressure in adolescents: reference ranges.

This descriptive population study of 307 public high school students, ages 15 to 17 years, was performed to establish reference ranges for orthostatic changes in heart rate and blood pressure in adolescents, and to identify influential variables. Noninvasive measurements of blood pressure and heart rate were obtained. Reference ranges for orthostatic heart rate change in this population at 2 minutes were -2 to +41 beats per minute and at 5 minutes were -1 to +48 beats per minute. Orthostatic blood pressure changes were within the adult range for 98% of adolescents tested. One-third of participants experienced orthostatic symptoms during testing. In conclusion, this study shows that orthostatic symptoms and large orthostatic heart rate changes occur in adolescents. This suggests that the current orthostatic heart rate criterion aiding the diagnosis of adult orthostatic intolerance syndromes is likely not appropriate for adolescents and should be reevaluated.