Monozygotic twins with myocarditis and a novel likely pathogenic desmoplakin gene variant.

Myocarditis most often affects otherwise healthy athletes and is one of the leading causes of sudden death in children and young adults. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically determined heart muscle disorder with increased risk for paroxysmal ventricular arrhythmias and sudden cardiac death. The clinical picture of myocarditis and ARVC may overlap during the early stages of cardiomyopathy, which may lead to misdiagnosis. In the literature, we found several cases that presented with episodes of myocarditis and ended up with a diagnosis of arrhythmogenic cardiomyopathy, mostly of the left predominant type. The aim of this case presentation is to shed light upon a possible link between myocarditis, a desmoplakin (DSP) gene variant, and ARVC by describing a case of male monozygotic twins who presented with symptoms and signs of myocarditis at 17 and 18 years of age, respectively. One of them also had a recurrent episode of myocarditis. The twins and their family were extensively examined including electrocardiograms (ECG), biochemistry, multimodal cardiac imaging, myocardial biopsy, genetic analysis, repeated cardiac magnetic resonance (CMR) and echocardiography over time. Both twins presented with chest pain, ECG with slight ST-T elevation, and increased troponin T levels. CMR demonstrated an affected left ventricle with comprehensive inflammatory, subepicardial changes consistent with myocarditis. The right ventricle did not appear to have any abnormalities. Genotype analysis revealed a nonsense heterozygous variant in the desmoplakin (DSP) gene [NM_004415.2:c.2521_2522del (p.Gln841Aspfs*9)] that is considered likely pathogenic and presumably ARVC related. There was no previous family history of heart disease. There might be a common pathophysiology of ARVC, associated with desmosomal dysfunction, and myocarditis. In our case, both twins have an affected left ventricle without any right ventricular involvement, and they are carriers of a novel DSP variant that is likely associated with ARVC. The extensive inflammation of the LV that was apparent in the CMR may or may not be the primary event of ARVC. Nevertheless, our data suggest that irrespective of a possible link here to ARVC, genetic testing for arrhythmogenic cardiomyopathy might be advisable for patients with recurrent myocarditis associated with a family history of myocarditis.

Changes in medication preceding out-of-hospital cardiac arrest where resuscitation was attempted.

OBJECTIVE: To describe recent changes in medication preceding out-of-hospital cardiac arrest (OHCA) where resuscitation was attempted. METHODS: OHCA victims were identified by the Swedish Cardiac Arrest Register and linked by means of their unique 10-digit personal identification numbers to the Prescribed Drug Register. We identified new claimed prescriptions during a 6-month period before the OHCA compared with those claimed in the period 12 to 18 months before. The 7-digit Anatomical Therapeutical Chemical codes of individual drugs were used. The study period was November 2007-January 2011. RESULTS: OHCA victims with drugs were (1) older than those who did not claim any drugs in any period (70 ± 16 years vs. 54 ± 22 years, P < 0.001), (2) more often women (34% vs. 20%, P < 0.001), and (3) had more often a presumed cardiac etiology (67% vs. 54%, P < 0.001). The OHCA victims were less likely to have ventricular tachycardia/ventricular fibrillation as the first recorded rhythm (26% vs. 33%, P < 0.001) or to survive 1 month (9% vs. 17%, P < 0.0001). New prescriptions were claimed by 5122 (71%) of 7243 OHCA victims. The most frequently claimed new drugs were paracetamol (acetaminophen) 10.3%, furosemide 7.8%, and omeprazole 7.6%. Of drugs known or supposed to cause QT prolongation, ciprofloxacin was the most frequent (3.4%) altogether; 16% had a new claimed prescription of a drug included in the "qtdrugs.org" lists. CONCLUSIONS: Most OHCA victims had new drugs prescribed within 6 months before the event but most often intended for diseases other than cardiac. No claims can be made as to the causality.

Who are the long-QT syndrome patients who receive an implantable cardioverter-defibrillator and what happens to them?: data from the European Long-QT Syndrome Implantable Cardioverter-Defibrillator (LQTS ICD) Registry.

BACKGROUND: A rapidly growing number of long-QT syndrome (LQTS) patients are being treated with an implantable cardioverter-defibrillator (ICD). ICDs may pose problems, especially in the young. We sought to determine the characteristics of the LQTS patients receiving an ICD, the indications, and the aftermath. METHODS AND RESULTS: The study population included 233 patients. Beginning in 2002, data were collected prospectively. Female patients (77%) and LQT3 patients (22% of genotype positive) were overrepresented; mean QTc was 516±65 milliseconds; mean age at implantation was 30±17 years; and genotype was known in 59% of patients. Unexpectedly, 9% of patients were asymptomatic before implantation. Asymptomatic patients, almost absent among LQT1 and LQT2 patients, represented 45% of LQT3 patients. Patients with cardiac symptoms made up 91% of all study participants, but only 44% had cardiac arrest before ICD implantation. In addition, 41% of patients received an ICD without having first been on LQTS therapy. During follow-up, 4.6±3.2 years, at least 1 appropriate shock was received by 28% of patients, and adverse events occurred in 25%. Appropriate ICD therapies were predicted by age <20 years at implantation, a QTc >500 milliseconds, prior cardiac arrest, and cardiac events despite therapy; within 7 years, appropriate shocks occurred in no patients with none of these factors and in 70% of those with all factors. CONCLUSIONS: Reflecting previous concepts, ICDs were implanted in some LQTS patients whose high risk now appears questionable. Refined criteria for implantation, reassessment of pros and cons, ICD reprogramming, and consideration for other existing therapeutic options are necessary.

Presumed arrhythmic death in consecutive survivors of acute myocardial infarction--implications for primary implantable cardioverter defibrillator implantation.

AIM: To describe the occurrence of arrhythmic death among survivors of acute myocardial infarction (AMI) and the availability of a primary implantable cardioverter defibrillator (ICD). METHODS: Consecutive patients who fulfilled the criteria for AMI admitted to the Sahlgrenska University Hospital during 21 months were prospectively followed for 2 years with a focus on echocardiography and mode of death. RESULTS: Among the 471 patients, for whom information on ejection fraction (EF) was available and who survived the first week, 10 patients died between days 7 and 30 - of whom one had an arrhythmic death. Among the 461 survivors on day 30, 34 patients (7.4%) had an EF of 30% or less. Among these, 24 were judged to be available for ICD implantation, of whom one died an arrhythmic death during follow-up. Among the remaining 10 patients who were excluded from ICD indication because of either high age and/or severe comorbidity, two patients died an arrhythmic death. Among the remaining 427 patients who had an EF greater than 30%, six died an arrhythmic death. Thus, 10 patients, with EF assessed, died an arrhythmic death between day 7 and 2 years after AMI, but only one would have received an ICD according to the Multicenter Automatic Defibrillator Implantation Trial II criteria and clinical judgement. CONCLUSION: Of the 471 consecutive survivors of AMI, 10 (2%) died an arrhythmic death, of whom only one would have received an ICD according to current guidelines and clinical judgement. Predictors of subsequent arrhythmic death after an AMI, useful on a per patient basis, remain an unmet need.

Interference of transcutaneous electrical nerve stimulation with permanent ventricular stimulation: a new clinical problem?

AIMS: To assess the compatibility of thoracic TENS and permanent PM treatment and to identify any signs of interference of TENS with the PM function. METHODS AND RESULTS: Twenty-seven patients treated with PM were tested. Transcutaneous electric nerve stimulation electrodes were placed above each mamilla, and the stimulation intensity was increased to the maximum level tolerated for 30 s or until electrocardiogram revealed signs of interference. Transcutaneous electric nerve stimulation of 2 and 80 Hz was tested with the PM ventricular sensing level set to the clinically chosen level as well as to maximal sensitivity. Interference was detected in 22 of 27 patients (81%). Low-frequency (2 Hz) stimulation was more associated with PM interference (52% at normal vs. 81% at maximal ventricular sensitivity) than high-frequency (80 Hz) stimulation (33% at normal vs. 63% at maximal ventricular sensitivity); although the differences were not statistically significant. CONCLUSION: Transcutaneous electric nerve stimulation frequently induces inhibition of the PM function already at the clinically set ventricular sensitivity. Therefore, individual testing is warranted before TENS treatment is considered in patients with a PM. A test protocol for TENS and PM interaction is proposed.

Rapid effects of air pollution on ventricular arrhythmias.

AIMS: Air pollution has been associated with ventricular arrhythmias in patients with implantable cardioverter defibrillators (ICDs) for exposure periods of 24-48 h. Only two studies have investigated exposure periods <24 h. We aimed to explore such effects during the 2 and 24 preceding hours as well as in relation to distance from the place of the event to the air pollution monitor. METHODS AND RESULTS: We used a case-crossover design to investigate the effects of particulate matter <10 microm in diameter (PM10) and nitrogen dioxide (NO2) in 211 patients with ICD devices in Gothenburg and Stockholm, Sweden. Events interpreted as ventricular arrhythmias were downloaded from the ICDs, and air pollution data were collected from urban background monitors. We found an association between 2 h moving averages of PM10 and ventricular arrhythmia [odds ratio (OR) 1.31, 95% confidence interval (CI) 1.00-1.72], whereas the OR for 24 h moving averages was 1.24 (95% CI 0.87-1.76). Corresponding ORs for events occurring closest to the air pollution monitor were 1.76 (95% CI 1.18-2.61) and 1.74 (95% CI 1.07-2.84), respectively. Events occurring in Gothenburg showed stronger associations than in Stockholm. CONCLUSION: Moderate increases in air pollution appear to be associated with ventricular arrhythmias in ICD patients already after 2 h, although future studies including larger numbers of events are required to confirm these findings. Representative geographical exposure classification seems important in studies of these effects.

Risk of interference from transcutaneous electrical nerve stimulation on the sensing function of implantable defibrillators.

BACKGROUND: The use of transcutaneous electrical nerve stimulation (TENS) for pain relief is increasing. At the same time the implantable cardioverter defibrillator (ICD) is a routine treatment for malignant tachyarrhythmias. Today patients often need devices for more than one condition, and consideration must be given to the interaction between them. We studied the risk of interference between TENS and the ICD function. METHODS AND RESULTS: Thirty patients who had received an ICD underwent a test protocol including TENS at the mammilla and hip levels, at two energy levels, and at the highest comfortable stimulation level. The effects of TENS on the electrocardiogram lead II, intracardiac electrograms, and the ICD marker channels were analyzed. Disturbance from TENS on the sensing function was seen at all stimulation attempts. Interference between the systems was observed in 16 patients. In eight patients (27%) the interpretation was VT/VF and in 14 patients (47%) as ventricular premature extra beats. Other kinds of interactions were seen in five patients (16%). Each patient could have more than one kind of interference. CONCLUSIONS: Noise reversion and undersensing might prevent the ICD from delivering shock when it should and the interpretation as VT/VF could result in inappropriate shocks. Because of the potentially serious consequences of interference we do not recommend the use of TENS in patients with ICD.