High Incidence of De Novo and Subclinical Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy and Cardiac Rhythm Management Device.

INTRODUCTION: Atrial fibrillation (AF) is an important prognostic parameter in patients with hypertrophic cardiomyopathy (HCM). Though cardiac rhythm management (CRM) devices (e.g., ICD, pacemaker or implantable loop recorder) can detect subclinical AF, data describing the incidence of AF are rare. We therefore investigated the incidence and clinical impact of de novo and subclinical AF detected by CRM devices in patients with HCM. METHODS AND RESULTS: In our retrospective single-center study, we included patients with HCM and need for CRM devices. The primary endpoint of the study was the incidence of clinical and subclinical de novo AF. During follow-up, patients were screened for adverse events like stroke, ventricular arrhythmia, heart failure, or death. From 192 HCM patients, 44 patients received a CRM device (38 ICDs, 5 pacemakers, 1 implantable loop recorder). In 14 of these patients (32%), AF had been documented before device implantation. Thirty (68%) patients were free from AF at the time of implantation. During a median follow-up of 595 days (interquartile range, 367-890 days), de novo AF was recorded in 16 of these 30 patients (53%). Fourteen (88%) of the 16 patients with de novo AF were free from any clinical symptoms, so these patients were classified to have subclinical AF. In logistic regression analysis, age was the only significant predictor for an increased risk of AF. CONCLUSION: AF is common in patients with HCM who need a CRM device. More than 50% of these patients develop de novo AF that was predominantly subclinical in our cohort.

Early segmental relaxation abnormalities in hypertrophic cardiomyopathy for differential diagnostic of patients with left ventricular hypertrophy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is characterized by asymmetric left ventricular hypertrophy (LVH). However, clinical signs can be subtle and differentiation from other causes of LVH is challenging. HYPOTHESIS: As diastolic dysfunction (DD) is an early sign in HCM, we aimed to find regional changes in relaxation pattern for differentiation from other entities of LVH. METHODS: In 148 patients (81 HCM, 55 arterial hypertension (AHT), 12 Fabry disease) and 63 healthy controls, relaxation patterns were assessed using regional tissue Doppler imaging. In 42 HCM patients, myocardial mass and fibrosis were quantified by cardiac magnetic resonance imaging and correlated with relaxation parameters. RESULTS: In HCM the septal to lateral isovolumic relaxation time (s/l IVRT) ratio was higher (1.5 ± 0.4) compared with AHT (1.1 ± 0.2), Fabry disease (1.0 ± 0.1), and controls (1.1 ± 0.2; P < 0.001), showing 77% sensitivity and 79% specificity to discriminate HCM-related LVH from other entities. The s/l IVRT ratio was independent of global DD in HCM (HCM with DD: 1.5 ± 0.5, n = 52; HCM without DD: 1.5 ± 0.3, n = 29) and remained significantly different from other entities in a subgroup of HCM patients with maximum wall thickness < 20 mm (s/l ratio: 1.5 ± 0.5, n = 28). Regional IVRT did not correlate with the corresponding segmental myocardial mass or amount of fibrosis in cardiac magnetic resonance imaging. CONCLUSIONS: HCM patients show a prolonged septal IVRT irrespective of the extent of LVH and even before developing global DD. The s/l IVRT ratio is significantly higher in HCM compared with AHT or Fabry disease, thus establishing segmental IVRT analysis as a potential parameter for differential diagnosis in LVH.

Hippocampal A-type current and Kv4.2 channel modulation by the sulfonylurea compound NS5806.

We examined the effects of the sulfonylurea compound NS5806 on neuronal A-type channel function. Using whole-cell patch-clamp we studied the effects of NS5806 on the somatodendritic A-type current (I(SA)) in cultured hippocampal neurons and the currents mediated by Kv4.2 channels coexpressed with different auxiliary ß-subunits, including both Kv channel interacting proteins (KChIPs) and dipeptidyl aminopeptidase-related proteins (DPPs), in HEK 293 cells. The amplitude of the I(SA) component in hippocampal neurons was reduced in the presence of 20 µM NS5806. I(SA) decay kinetics were slowed and the recovery kinetics accelerated, but the voltage dependence of steady-state inactivation was shifted to more negative potentials by NS5806. The peak amplitudes of currents mediated by ternary Kv4.2 channel complexes, associated with DPP6-S (short splice-variant) and either KChIP2, KChIP3 or KChIP4, were potentiated and their macroscopic inactivation slowed by NS5806, whereas the currents mediated by binary Kv4.2 channels, associated only with DPP6-S, were suppressed, and the NS5806-mediated slowing of macroscopic inactivation was less pronounced. Neither potentiation nor suppression and no effect on current decay kinetics in the presence of NS5806 were observed for Kv4.2 channels associated with KChIP3 and the N-type inactivation-conferring DPP6a splice-variant. For all recombinant channel complexes, NS5806 slowed the recovery from inactivation and shifted the voltage dependence of steady-state inactivation to more negative potentials. Our results demonstrate the activity of NS5806 on native I(SA) and possible molecular correlates in the form of recombinant Kv4.2 channels complexed with different KChIPs and DPPs, and they shed some light on the mechanism of NS5806 action.