Objective:

During the course of acute rheumatic fever, some electrocardiographic changes are seen. First-degree atrioventricular block is the most common electrocardiographic abnormality. Second- and third-degree atrioventricular block, ventricular tachycardia, and junctional acceleration are also seen. In the present study, the specificity of accelerated junctional rhythm to acute rheumatic fever was investigated.

Methods:

The study included patients with acute rheumatic fever (Group 1), healthy children who had suffered from recent group A β-haemolytic streptococcal upper respiratory tract infection but did not develop acute rheumatic fever (Group 2), and patients who had other diseases that may affect the joints and/or heart (Group 3).

Results:

Accelerated junctional rhythm was detected in 10 patients in Group 1, but in none of the patients from Group 2 or 3. Specificity of accelerated junctional rhythm for acute rheumatic fever was 100% and the positive predictive value was 100%.

Conclusion:

Accelerated junctional rhythm is specific to acute rheumatic fever. Although its frequency is low, it seems that it can be used in the differential diagnosis of acute rheumatic fever, especially in patients with isolated polyarthritis.

Atazanavir is one highly active antiretroviral therapy for naïve patients or patients with previous regimen failure. However, it seems that the protease inhibitor induces hyperlipidemia. Hyperbillirubinemia is the most common clinical adverse events but reports of cardiotoxicity due to atazanavir are scarce. The authors report a patient who had QT prolongation, first-degree atrioventricularblock, and ventricular tachycardia. After atazanavir/ritonavir discontinuation, this patient got better and had normal electrocardiography. Lopinavir/ritonavir was carefully reintroduced during hospitalization without any adverse drug reaction. Atazanavir induced cardiotoxicity has to be monitored when using protease inhibitors.

The presence of 2 distinct populations of somatic or germline cells within a single individual harboring different genotypes is termed mosaicism. Recent reports suggest that parental mosaicism is involved in the heritability of type 1 Timothy syndrome (TS1), an extremely rare and life-threatening multisystem disorder characterized by severe QT interval prolongation, syndactyly, and several other complications. Although full TS1 is caused by a single missense mutation in the CACNA1C-encoded cardiac calcium channel, mosaic TS1 parents can display isolated syndactyly without additional phenotypic manifestations. A newborn boy presented with syndactyly at birth. The presence of syndactyly in his mother led to a diagnosis of benign familial syndactyly. However, at 9 months of age, during his first syndactyly-corrective surgery, intraoperative electrocardiograms revealed extreme QT prolongation and 2:1 atrioventricular block. A comprehensive cardiac evaluation was performed, and both mother and child were tested genetically, confirming a clinical suspicion of TS1. Only the patient tested positive for the TS1 mutation; however, more extensive molecular testing revealed a limited presence of the mutation in maternally-derived DNA. This case illustrates the potential of parental mosaicism to confound the diagnosis of potentially life-threatening genetic diseases, such as TS1. Here, a mother with a partial TS1 phenotype and genetically confirmed mosaicism transmitted the TS1-causative mutation to her son, resulting in fully expressive TS1. Thus, a shared partial phenotype should not be dismissed as a benign or insignificant finding, but should be evaluated further to rule out the possibility of parental mosaicism concealing a potentially fatal heritable disease.

OBJECTIVE:

This study tested the hypothesis that inducing an autoimmune response against the cardiac sodium channel (NaV1.5) induces arrhythmias.

BACKGROUND:

Sporadical evidence supports the concept that autoantibodies may cause cardiac arrhythmias but substantial experimental investigations using in vivo models have been lacking to date. The NaV1.5 is essential for cardiac impulse propagation and its dysfunction has been linked to conduction disease.

METHODS:

Rats were immunized with a peptide sequence derived from the third extracellular loop of the first domain of NaV1.5. After 28 days, we evaluated in vivo both the electrical and mechanical parameters of cardiac function. Histopathology, myocardial gene and protein expression were assessed. Whole-cell patch-clamp was used to measure sodium current (INa) density in isolated cardiomyocytes.

RESULTS:

NaV1.5-immunized rats had high titers of autoantibodies against NaV1.5. On ECG recording, NaV1.5-immunized animals showed significantly prolonged PR-intervals. During holter ECG-monitoring we observed repeated prolonged episodes of third-degree atrioventricular and sinoatrial block in every NaV1.5-immunized animal, but not in controls. Immunization had no effect on cardiac function. In comparison to controls, myocardial NaV1.5 mRNA and protein levels were decreased in immunized rats. INa density was reduced in cardiomyocytes incubated with sera from NaV1.5-immunized rats and from patients with idiopathic atrioventricular block (AVB) in comparison to sera from respective controls. In patients with idiopathic AVB, we observed autoantibodies against NaV1.5 that were absent in sera from healthy controls.

CONCLUSIONS:

Provocation of an autoimmune response against NaV1.5 induces conductance defects probably caused by a reduced expression level and an inhibition of NaV1.5 by autoantibodies, resulting in decreased INa.

The aim of this study was to analyze survival, causes of death and cardiologic predictors of sudden death in a large cohort of patients with myotonic dystrophy type 1 (DM1). The study was comprised of 171 adult DM1 patients hospitalized at the Neurology Clinic in a 20-year period. Severe electrocardiographic (ECG) abnormality included at least one of the following: rhythm other than sinus, PR interval of ⩾240ms, QRS complex duration of 120ms or more, and second-degree or third-degree atrioventricular (AV) block. Survival data were analyzed by the Kaplan-Meier test, log-rank test and Cox regression analysis. During the mean follow-up period of 9.4±5.4years, a pacemaker was implanted in 5.8% of DM1 patients and 14% of patients died. The mean age at death was 55.6±12.5years. The most common causes of death in our cohort were sudden death (41.7%) and respiratory failure (29.2%). The presence of palpitations (hazard ratio [HR]=4.7, p<0.05) and increased systolic blood pressure (HR=9.8, p<0.05) were significant predictors of sudden death. Among ECG parameters, severe ECG abnormality (HR=4.7, p<0.05), right bundle branch block (RBBB; HR=3.9, p<0.05) and bifascicular block (HR=5.8, p<0.05) were significant predictors of sudden death.

Development of dilated cardiomyopathy in patients with congenital complete atrioventricular block with or without pacemaker is well described. We report a case of dilated cardiomyopathy in a child with congenital complete atrioventricular block, long-QT syndrome, and VVI pacemaker. Temporary pacing in the right ventricular outflow tract demonstrated a 63% increase in cardiac output. After change to biventricular DDD pacing, left ventricular systolic function and diastolic dimensions normalised.

The present study was designed to investigate whether microRNAs (miRNAs) are involved in atrioventricular block (AVB) in the setting of myocardial ischemia (MI). A cardiac-specific miR-1 transgenic (Tg) mouse model was successfully established for the first time in this study using microinjection. miR-1 level was measured by real-time qRT-PCR. Whole-cell patch clamp was employed to record L-type calcium current (I Ca,L) and inward rectifier K(+) current (I K1). Expression of connexin 43 (Cx43) protein was determined by western blot analysis. Alternations of [Ca(2+)]i was detected by laser scanning confocal microscopy in ventricular myocytes. The incidence of AVB was higher in miR-1 Tg mice than that in wild-type (WT) mice. The normalized peak current amplitude of I Ca,L was lower in ventricular myocytes from miR-1 Tg mice as compared with WT mice. Similarly, the current density of I K1 was decreased in miR-1 Tg mice than that in WT mice. Compared with WT mice, miR-1 Tg mice exhibited a significant decrease of the systolic [Ca(2+)]i in ventricular myocytes but a prominent increase of the resting [Ca(2+)]i. Moreover, Cx43 protein was downregulated in miR-1 Tg mice compared to that in WT mice. Administration of LNA-modified antimiR-1 reversed all the above changes. miR-1 overexpression may contribute to the increased susceptibility of the heart to AVB, which provides us novel insights into the molecular mechanisms underlying ischemic cardiac arrhythmias.

Simultaneous thrombosis of more than one coronary artery is an uncommon angiographic finding in acute ST-segment elevation myocardial infarction (STEMI), and usually leads to cardiogenic shock or even sudden cardiac death. We reported a 56-year-old man presenting with persistent chest tightness and ST-segment elevation over precordial leads in electrocardiography (ECG). Emergent coronary angiogram showed total occlusion of both the proximal right coronary artery (RCA) and the proximal left anterior descending artery (LAD). We performed thrombus aspiration and stenting over the LAD with thrombolysis in myocardial infarction (TIMI) III flow to the distal LAD. However, diminishing collateral flow to the distal RCA complicated with complete atrioventricular block (CAVB) and cardiogenic shock developed thereafter. Because distal embolization of the collateral circulation from the LAD to the distal RCA was suspected, thrombus aspiration and stenting over the proximal RCA were performed. After reperfusion of the RCA, the patient's hemodynamic status stabilized and he recovered uneventfully.

BACKGROUND:

The study was undertaken to assess the properties of mouse HCN4 (mHCN4)-modified canine mesenchymal stem cells (cMSCs) in dogs with experimentally induced complete atrioventricular (AV) block and electronic pacing.

METHODS:

Complete AV block was induced in adult dogs who had undergone implantation of backup electronic pacemakers. cMSCs were transfected with mHCN4 genes. Evidence of successful IHCN4 expression was provided by patch-clamp detection. mHCN4-cMSCs or normal cMSCs were injected subepicardially into the left ventricular anterior wall of the dogs. Cardiac parameters were monitored for 6 weeks. Heart rate variability (HRV) was evaluated using quantitative Poincaré plots of R-RN against R-RN+1 intervals. cMSCs survival and expression of HCN4 in vivo were examined by histological studies and Western blot.

RESULTS:

In 2 weeks, the maximum heart rate and the number of impulses generated from the injection sites were much higher in dogs injected with HCN4-modified MSCs than in control dogs.  Basal heart rate increased in the HCN4 group and became fully stabilized by Week 4, evidenced by markedly reduced numbers of electronic pacemaker beats. At Week 2, HRV during exercise was significantly higher in HCN4 dogs than in controls as shown by descriptors of both instantaneous (SD1) and longer term (SD2) beat-to-beat deviations (P < 0.05). Hematoxylin-eosin staining and Western blot proved that cMSCs survive and express HCN4 protein in situ in heart of HCN4 dog.

CONCLUSION:

Transplantation of mHCN4-modified cMSCs provided a stable biological pacemaking function that allowed an appropriate chronotropic response to physical exercise for up to 6 weeks.

BACKGROUND:

AutoCapture™ (AC) of St. Jude Medical (SJM; St. Paul, MN, USA) pacemakers provides beat-to-beat ventricular capture verification and allows low-amplitude pacing. There has been concern about evoked response signal (ERS) amplitude decreasing over time, leading to discontinuation of AC. The purpose of this study was to evaluate the long-term performance of AC in infants with epicardial pacing leads.

METHODS:

Data on 16 newborns with congenital complete atrioventricular block (CCAVB) implanted with a SJM Microny pacemaker between January 1998 and December 2004 were collected. The ERS at discharge, at 12 ± 2 months, and long-term AC performance were analyzed retrospectively. The median follow-up time was 5.3 years (range 0.4-8.6 years), the end point of follow-up being either lead or generator exchange.

RESULTS:

AC could be activated in all patients at discharge; the median ERS was 9.3 mV (3.7-19.0 mV). At 12 ± 2 months, the median ERS measured 4.6 ± 3.6 mV (n = 13), showing a significant decrease (P = 0.002) and leading to discontinuation of AC in three (23%) of 13 patients. AC use was possible in eight patients and long-term use in six patients.

CONCLUSIONS:

In epicardially paced CCAVB newborns, the ERS amplitude decreased significantly during the first year. ERS decrease was the most common reason for AC failure. At 1-year follow-up, AC was functional in only 53% of patients, although it could originally be activated in all patients. During the first year of follow-up, special attention to AC parameters is recommended in this subgroup of pediatric pacemaker patients.