Giant Cardiac Fibroma: An Unusual Cause of Failure to Thrive

Cardiac fibromas are extremely rare in the general pediatric population and may present with a wide spectrum of clinical signs, including life-threatening arrhythmias and sudden death. We report a 14-month-old boy who presented with failure to thrive as the only symptom. Echocardiography showed a large cardiac fibroma in the right ventricle. Cardiac magnetic resonance imaging confirmed the diagnosis. After complete surgical tumor resection, the boy showed normal catch-up growth. This case underlines the diversity of clinical features of cardiac tumors, which implies that they should be considered early in the differential diagnosis of infants with failure to thrive.

Cardiac tissue-restricted deletion of plakoglobin results in progressive cardiomyopathy and activation of {beta}-catenin signaling

Mutations in the plakoglobin (JUP) gene have been identified in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients. However, the mechanisms underlying plakoglobin dysfunction involved in the pathogenesis of ARVC remain poorly understood. Plakoglobin is a component of both desmosomes and adherens junctions located at the intercalated disc (ICD) of cardiomyocytes, where it functions to link cadherins to the cytoskeleton. In addition, plakoglobin functions as a signaling protein via its ability to modulate the Wnt/beta-catenin signaling pathway. To investigate the role of plakoglobin in ARVC, we generated an inducible cardiorestricted knockout (CKO) of the plakoglobin gene in mice. Plakoglobin CKO mice exhibited progressive loss of cardiac myocytes, extensive inflammatory infiltration, fibrous tissue replacement, and cardiac dysfunction similar to those of ARVC patients. Desmosomal proteins from the ICD were decreased, consistent with altered desmosome ultrastructure in plakoglobin CKO hearts. Despite gap junction remodeling, plakoglobin CKO hearts were refractory to induced arrhythmias. Ablation of plakoglobin caused increase beta-catenin stabilization associated with activated AKT and inhibition of glycogen synthase kinase 3beta. Finally, beta-catenin/TCF transcriptional activity may contribute to the cardiac hypertrophy response in plakoglobin CKO mice. This novel model of ARVC demonstrates for the first time how plakoglobin affects beta-catenin activity in the heart and its implications for disease pathogenesis.

A locus on chromosome 5 is associated with dilated cardiomyopathy in Doberman Pinschers

Dilated cardiomyopathy (DCM) is a heterogeneous group of heart diseases with a strong genetic background. Currently, many human DCM cases exist where no causative mutation can be identified. DCM also occurs with high prevalence in several large dog breeds. In the Doberman Pinscher a specific DCM form characterized by arrhythmias and/or echocardiographic changes has been intensively studied by veterinary cardiologists. We performed a genome-wide association study in Doberman Pinschers. Using 71 cases and 70 controls collected in Germany we identified a genome-wide significant association to DCM on chromosome 5. We validated the association in an independent cohort collected in the United Kingdom. There is no known DCM candidate gene under the association signal. Therefore, DCM in Doberman Pinschers offers the chance of identifying a novel DCM gene that might also be relevant for human health.

The esophageal ECG as a novel technique for ambulant heart rhythm monitoring

Introduction: Diagnosing arrhythmias by conventional Holter-ECG can be cumbersome because of artifacts, skin irritation and poor P-waves. In contrast, esophageal electrocardiography (eECG) is promising due to the anatomic relationship of the esophagus to the atria and its favorable bioelectric properties. Methods used: In an ambulant setting, we recorded eECGs from 10 volunteers with a novel, highly-miniaturized eECG recorder that is worn discretely behind the ear (1.5×1.8×5cm, 22grams). The device continuously records two eECG leads during 3 days with 500Hz sampling frequency and 24-bit resolution. Results: Mean ± SD recording time was 21.7±19.6 hours (max. 60 hours). Test persons were not limited in daily activities (e.g. eating, speaking) and only complained mild discomfort during probe insertion, which subsided later on. During 99.8% of time, the recorder acquired signals appropriate for further analysis. In unfiltered data, QRS complexes and P-waves were identifiable during >98% of time. P waves had higher amplitudes as compared to surface ECG (0.71 ± 0.42mV vs. 0.16 ± 0.03mV, p = 0.004). No complications occurred. Conclusion: Ambulatory eECG recording is safe, well tolerated and promising due to excellent P-wave detection, overcoming some limitations of conventional Holter ECG.

Inflammation and atrial remodeling after a mountain marathon

Endurance athletes have an increased risk of atrial fibrillation. We performed a longitudinal study on elite runners of the 2010 Jungfrau Marathon, a Swiss mountain marathon, to determine acute effects of long-distance running on the atrial myocardium. Ten healthy male athletes were included and examined 9 to 1 week prior to the race, immediately after, and 1, 5, and 8 days after the race. Mean age was 34.9 ± 4.2 years, and maximum oxygen consumption was 66.8 ± 5.8 mL/kg*min. Mean race time was 243.9 ± 17.7 min. Electrocardiographic-determined signal-averaged P-wave duration (SAPWD) increased significantly after the race and returned to baseline levels during follow-up (128.7 ± 10.9 vs. 137.6 ± 9.8 vs. 131.5 ± 8.6 ms; P < 0.001). Left and right atrial volumes showed no significant differences over time, and there were no correlations of atrial volumes and SAPWD. Prolongation of the SAPWD was accompanied by a transient increase in levels of high-sensitivity C-reactive protein, proinflammatory cytokines, total leucocytes, neutrophil granulocytes, pro atrial natriuretic peptide and high-sensitivity troponin. In conclusion, marathon running was associated with a transient conduction delay in the atria, acute inflammation and increased atrial wall tension. This may reflect exercise-induced atrial myocardial edema and may contribute to atrial remodeling over time, generating a substrate for atrial arrhythmias.

TRPM4 channels in the cardiovascular system: physiology, pathophysiology, and pharmacology

The transient receptor potential channel (TRP) family comprises at least 28 genes in the human genome. These channels are widely expressed in many different tissues, including those of the cardiovascular system. The transient receptor potential channel melastatin 4 (TRPM4) is a Ca(2+)-activated non-specific cationic channel, which is impermeable to Ca(2+). TRPM4 is expressed in many cells of the cardiovascular system, such as cardiac cells of the conduction pathway and arterial and venous smooth muscle cells. This review article summarizes the recently described roles of TRPM4 in normal physiology and in various disease states. Genetic variants in the human gene TRPM4 have been linked to several cardiac conduction disorders. TRPM4 has also been proposed to play a crucial role in secondary hemorrhage following spinal cord injuries. Spontaneously hypertensive rats with cardiac hypertrophy were shown to over-express the cardiac TRPM4 channel. Recent studies suggest that TRPM4 plays an important role in cardiovascular physiology and disease, even if most of the molecular and cellular mechanisms have yet to be elucidated. We conclude this review article with a brief overview of the compounds that have been shown to either inhibit or activate TRPM4 under experimental conditions. Based on recent findings, the TRPM4 channel can be proposed as a future target for the pharmacological treatment of cardiovascular disorders, such as hypertension and cardiac arrhythmias.

Training-related modulations of the autonomic nervous system in endurance athletes: is female gender cardioprotective?

The risk of sudden death is increased in athletes with a male predominance. Regular physical activity increases vagal tone, and may protect against exercise-induced ventricular arrhythmias. We investigated training-related modulations of the autonomic nervous system in female and male endurance athletes. Runners of a 10-mile race were invited. Of 873 applicants, 68 female and 70 male athletes were randomly selected and stratified according to their average weekly training hours in a low (≤4 h) and high (>4 h) volume training group. Analysis of heart rate variability was performed over 24 h. Spectral components (high frequency [HF] and low frequency [LF] power in normalized units) were analyzed for hourly 5 min segments and averaged for day- and nighttime. One hundred and fourteen athletes (50 % female, mean age 42 ± 7 years) were included. No significant gender difference was observed for training volume and 10-mile race time. Over the 24-h period, female athletes exhibited a higher HF and lower LF power for each hourly time-point. Female gender and endurance training hours were independent predictors of a higher HF and lower LF power. In female athletes, higher training hours were associated with a higher HF and lower LF power during nighttime. In male athletes, the same was true during daytime. In conclusion, female and male athletes showed a different circadian pattern of the training-related increase in markers of vagal tone. For a comparable amount of training volume, female athletes maintained their higher markers of vagal tone, possibly indicating a superior protection against exercise-induced ventricular arrhythmias.

Heterogeneous response of J-wave syndromes to beta-adrenergic stimulation

Inferolateral early repolarization (ER) and Brugada syndrome manifest with J waves. Isoproterenol suppresses recurrent ventricular arrhythmias while reducing J waves in both disorders.

Dual-loop circuits in postoperative atrial macro re-entrant tachycardias

Background Patients late after open-heart surgery may develop dual-loop reentrant atrial arrhythmias, and mapping and catheter ablation remain challenging despite computer-assisted mapping techniques. Objectives The purpose of the study was to demonstrate the prevalence and characteristics of dual-loop reentrant arrhythmias, and to define the optimal mapping and ablation strategy. Methods Fourty consecutive patients (mean age 52+/-12 years) with intra-atrial reentrant tachycardia (IART) after open-heart surgery (with an incision of the right atrial free wall) were studied. Dual-loop IART was defined as the presence of two simultaneous atrial circuits. Following an abrupt tachycardia change during radiofrequency (RF) ablation, electrical disconnection of the targeted reentry isthmus from the remaining circuit was demonstrated by entrainment mapping. Furthermore, the second circuit loop was localized using electroanatomic mapping and/or entrainment mapping. Results Dual-loop IART was demonstrated in 8 patients (20%, 5 patients with congenital heart disease, 3 with acquired heart disease). Dual-loop IART included an isthmus-dependant atrial flutter combined with a reentry related to the atriotomy scar. The diagnosis of dual-loop IART required the comparison of entrainment mapping before and after tachycardiamodification. Overall, 35 patients had successful RF ablation (88%). Success rates were lower in patients with dual-loop IART than in patient without dual-loop IART. Ablation failures in 3 patients with dual-loop IART were related to the inability to properly transect the second tachycardia isthmus in the right atrial free wall. Conclusions Dual-loop IART is relatively common after heart surgery involving a right atriotomy. Abrupt tachycardia change and specific entrainment mapping maneuvers demonstrate these circuits. Electroanatomic mapping appears to be important to assist catheter ablation of periatriotomy circuits.

Seasonal variations of ventricular arrhythmia clusters in defibrillator recipients

BACKGROUND: Clustering ventricular arrhythmias are the consequence of acute ventricular electrical instability and represent a challenge in the management of the growing number of patients with an implantable cardioverter-defibrillator (ICD). Triggering factors can rarely be identified. OBJECTIVES: Several studies have revealed seasonal variations in the frequency of cardiovascular events and life-threatening arrhythmias, and we sought to establish whether seasonal factors may exacerbate ventricular electrical instability leading to arrhythmia clusters and electrical storm. METHODS: Two hundred and fourteen consecutive defibrillator recipients were followed-up during 3.3 +/- 2.2 years. Arrhythmia cluster was defined as the occurrence of three or more arrhythmic events triggering appropriate defibrillator therapies within 2 weeks. Time intervals between two clusters were calculated for each month and each season, and were compared using Kruskal-Wallis test and Wilcoxon-Mann-Whitney test with Bonferroni adjustment. RESULTS: During a follow-up of 698 patient years, 98 arrhythmia clusters were observed in 51 patients; clustering ventricular arrhythmias were associated with temporal variables; they occurred more frequently in the winter and spring months than during the summer and fall. Accordingly, the time intervals between two clusters were significantly shorter during winter and spring (median and 95% CI): winter 16 (5-19), spring 11.5 (7-25), summer 34.5 (15-55), fall 50.5 (19-65), P = 0.0041. CONCLUSION: There are important seasonal variations in the incidence of arrhythmia clusters in ICD recipients. Whether these variations are related to environmental factors, change in physical activity, or psychological factors requires further study.

Intracardiac devices for stroke prevention

Stroke is a significant cause of serious disability and death worldwide. A substantial proportion of strokes are related to an underlying cardiac embolic source, most commonly in association with atrial arrhythmias (fibrillation/flutter). Atrial fibrillation is considered a major risk factor for stroke. Although long-term prophylactic oral anticoagulation has been shown to be very effective in reducing stroke in patients with atrial fibrillation, it has a number of major limitations and is not feasible in all patients. In such cases, the use of percutaneously (transvenous) implanted left atrial appendage occlusive devices or surgical appendage obliteration is being explored. Similarly, the presence of a patent foramen ovale, especially in the presence of an atrial septal aneurysm, is now recognized as an important potential mediator of paradoxical cardiogenic embolism. Percutaneous patent foramen ovale closure is becoming increasingly established as a safe and effective means of preventing recurrent strokes in the presence of a patent foramen ovale. In this account, the authors discuss the intracardiac devices and techniques available and the relative merits of their use for stroke prevention.

Safety and exercise tolerance of acute high altitude exposure (3454 m) among patients with coronary artery disease

OBJECTIVES: To assess the safety and cardiopulmonary adaptation to high altitude exposure among patients with coronary artery disease. METHODS: 22 patients (20 men and 2 women), mean age 57 (SD 7) years, underwent a maximal, symptom limited exercise stress test in Bern, Switzerland (540 m) and after a rapid ascent to the Jungfraujoch (3454 m). The study population comprised 15 patients after ST elevation myocardial infarction and 7 after a non-ST elevation myocardial infarction 12 (SD 4) months after the acute event. All patients were revascularised either by percutaneous coronary angioplasty (n = 15) or by coronary artery bypass surgery (n = 7). Ejection fraction was 60 (SD 8)%. beta blocking agents were withheld for five days before exercise testing. RESULTS: At 3454 m, peak oxygen uptake decreased by 19% (p < 0.001), maximum work capacity by 15% (p < 0.001) and exercise time by 16% (p < 0.001); heart rate, ventilation and lactate were significantly higher at every level of exercise, except at maximum exertion. No ECG signs of myocardial ischaemia or significant arrhythmias were noted. CONCLUSIONS: Although oxygen demand and lactate concentrations are higher during exercise at high altitude, a rapid ascent and submaximal exercise can be considered safe at an altitude of 3454 m for low risk patients six months after revascularisation for an acute coronary event and a normal exercise stress test at low altitude.

Reduced atrial connexin43 expression after pediatric heart surgery

Myocardial dysfunction and arrhythmias may be induced by congenital heart defects, but also be the result of heart surgery with cardiopulmonary bypass (CPB), potentially caused by differential expression of connexin40 (Cx40) and connexin43 (Cx43). In 16 pediatric patients undergoing corrective heart surgery, connexin mRNA expression was studied in volume overloaded (VO group, n=8) and not overloaded (NO group, n=8) right atrial myocardium, excised before and after CPB. Additionally, in eight of these patients ventricular specimens were investigated. The atrial Cx43 expression decreased during CPB, which was restricted to the VO group (p=0.008). In contrast, atrial Cx40 mRNA did not change during CPB. In ventricular myocardium compared to atrial mRNA levels, Cx40 was lower (p=0.006) and Cx43 higher (p=0.017) expressed, without significant change during CPB. This study revealed a significant influence of CPB and the underlying heart defect on Cx43 expression.

Radiofrequency ablation in children and adolescents: results in 154 consecutive patients

AIMS: The experience of using radiofrequency ablation (RFA) for the treatment of arrhythmias in children and adolescents is still limited. This study aimed to review the most recent results of RF ablation in children and adolescents in a highly experienced centre with access to both conventional techniques and non-fluoroscopic electroanatomic mapping (CARTO). METHODS AND RESULTS: A total of 154 consecutive patients younger than 19 years treated with RFA during the period 2000-04 were included. Numbers (%) or median (quartiles) are reported. Age was 15 (12-17) years, 70 (45%) were males. Five patients (3%) had congenital heart disease. RFA was successful in 147/154 patients (95%). Arrhythmia recurrence occurred in 11 patients (7%). Procedure time was 55 (35-90) min and fluoroscopy time was 8.8 (4-19) min. Number of RF applications was 4 (2-10) and number of RF applications >20 s was 2 (1-7). One patient (0.7%) had complicating high-grade atrioventricular block. CARTO was used in 18 RF ablation procedures (11%) performed in 15 patients. CONCLUSION: RF ablation can be undertaken in children and adolescents with a high success rate, few recurrences and complications, very short procedure times, and acceptable fluoroscopy times. Non-fluoroscopic electroanatomic mapping is helpful in selected patients.

F90927: a new member in the class of cardioactive steroids

F90927 is a newly developed cardioactive drug with a steroid-like structure. It acts directly and agonistically on the cardiac L-type Ca2+ channel by shifting its voltage-dependent activation toward more negative potentials. This leads to an increased influx of Ca2+ and, therefore, to a stronger contraction; however, no arrhythmias occur. Calcium current stimulation can already be observed at nanomolar concentrations, but higher concentrations of F90927 elevate intracellular Ca2+ concentration, causing a reduction of the myocardial compliance and an increased diastolic blood pressure. Vessels also react to F90927 and contract in its presence. Binding of F90927 with the L-type Ca2+ channel presumably occurs in the vicinity of the transmembrane domains III and IV of the alpha1 subunit. F90927 exhibits no use dependence and interacts with Ca2+ channel inhibitors of all three known classes of channel modulators (dihydropyridines, phenylalkylamines, and benzothiazepines), suggesting that it is a member of a new class of Ca2+ channel modulators. Due to its adverse effects on blood pressure and vessel contraction, F90927 is not an ideal drug candidate. It has, however, some unique properties, which makes it a promising tool to study the function of the L-type Ca2+ channel.