Publications by authors named "Jan Till"

ASP8302 is an orally administered positive allosteric modulator of the muscarinic M receptor. Two Phase 1 studies were conducted, a first-in-human study in Europe and a Japanese phase 1 study. Both were randomized, participant- and investigator-blinded, placebo-controlled, single and multiple ascending oral doses, parallel group, clinical studies in healthy volunteers.

View Article and Find Full Text PDF

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) may cause sudden cardiac death (SCD) despite medical therapy. Therefore, implantable cardioverter-defibrillators (ICDs) are commonly advised. However, there is limited data on the outcomes of ICD use in children.

View Article and Find Full Text PDF
Article Synopsis
  • Calmodulinopathy is caused by mutations in CALM genes and leads to serious arrhythmias, particularly in young people; the ICalmR aims to connect clinical symptoms with molecular causes.
  • The ICalmR has gathered data from 140 patients, showing a notable presence of CALM-LQTS and CALM-CPVT, and has observed a decrease in the frequency of serious cardiac events compared to past data.
  • The condition presents a wide range of symptoms, from severe arrhythmias to no symptoms at all; while therapy options are limited and based on current practices, management often involves medication and devices like defibrillators.
View Article and Find Full Text PDF

Oral propranolol therapy is commonly used for the prevention of tachyarrhythmias in infancy and childhood. Propranolol is commercially produced in four concentrations allowing varying volumes to be administered. However, quite often an alternative strength of propranolol liquid is issued without clear change in instructions or warning.

View Article and Find Full Text PDF

Aim: The aim of this study is to evaluate safety and efficacy of ASP8302, a novel positive allosteric modulator for the muscarinic M3 receptor (M3-PAM), in patients with underactive bladder (UAB).

Methods: A randomized, double-blind, placebo-controlled multicenter study was performed in adult male/female subjects with UAB, defined as incomplete bladder emptying (postvoid residual volume [PVR] > 100 ml) without significant bladder outlet obstruction and/or overactive bladder. Subjects were randomized (1:1) to receive 4-week oral once-daily administration of 100 mg ASP8302 or matching placebo.

View Article and Find Full Text PDF

Background: Conventional superior access for cardiac implantable electronic devices (CIEDs) is not always possible and femoral CIEDs (F-CIED) are an alternative option when leadless systems are not suitable. The long-term outcomes and extraction experiences with F-CIEDs, in particular complex F-CIED (ICD/CRT devices), remain poorly understood.

Methods: Patients referred for F-CIEDs implantation between 2002 and 2019 at two tertiary centers were included.

View Article and Find Full Text PDF

Background: Symptomatic children with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for recurrent arrhythmic events. β-Blockers decrease this risk, but studies comparing individual β-blockers in sizeable cohorts are lacking. We aimed to assess the association between risk for arrhythmic events and type of β-blocker in a large cohort of symptomatic children with CPVT.

View Article and Find Full Text PDF

Importance: Calcium-release deficiency syndrome (CRDS), which is caused by loss-of-function variants in cardiac ryanodine receptor 2 (RyR2), is an emerging cause of ventricular fibrillation. However, the lack of complex polymorphic/bidirectional ventricular tachyarrhythmias during exercise stress testing (EST) may distinguish it from catecholaminergic polymorphic ventricular tachycardia (CPVT). Recently, in the first clinical series describing the condition, mouse and human studies showed that the long-burst, long-pause, short-coupled ventricular extra stimulus (LBLPS) electrophysiology protocol reliably induced CRDS ventricular arrhythmias.

View Article and Find Full Text PDF

Purpose: Biallelic hypomorphic variants in PPA2, encoding the mitochondrial inorganic pyrophosphatase 2 protein, have been recently identified in individuals presenting with sudden cardiac death, occasionally triggered by alcohol intake or a viral infection. Here we report 20 new families harboring PPA2 variants.

Methods: Synthesis of clinical and molecular data concerning 34 individuals harboring five previously reported PPA2 variants and 12 novel variants, 11 of which were functionally characterized.

View Article and Find Full Text PDF

Objectives: This study set out to examine outcomes from pediatric supraventricular tachycardia ablations over a 20-year period. This study sought to examine success rates and repeat ablations over time and to evaluate whether modalities such as 3-dimensional (3D) mapping, contact force, and cryotherapy have improved outcomes.

Background: Ablation of supraventricular tachycardia in pediatric patients is commonly performed in most congenital heart centers with excellent long-term results.

View Article and Find Full Text PDF

Aims: Sudden cardiac death (SCD) is the most common mode of death in paediatric hypertrophic cardiomyopathy (HCM). This study describes the implant and programming strategies with clinical outcomes following implantable cardioverter-defibrillator (ICD) insertion in a well-characterized national paediatric HCM cohort.

Methods And Results: Data from 90 patients undergoing ICD insertion at a median age 13 (±3.

View Article and Find Full Text PDF

Background: Genetic variants in calsequestrin-2 () cause an autosomal recessive form of catecholaminergic polymorphic ventricular tachycardia (CPVT), although isolated reports have identified arrhythmic phenotypes among heterozygotes. Improved insight into the inheritance patterns, arrhythmic risks, and molecular mechanisms of -CPVT was sought through an international multicenter collaboration.

Methods: Genotype-phenotype segregation in -CPVT families was assessed, and the impact of genotype on arrhythmic risk was evaluated using Cox regression models.

View Article and Find Full Text PDF

Background: Risk stratification in catecholaminergic polymorphic ventricular tachycardia remains ill defined. Heart rate recovery (HRR) immediately after exercise is regulated by autonomic reflexes, particularly vagal tone, and may be associated with symptoms and ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia. Our objective was to evaluate whether HRR after maximal exercise on the exercise stress test (EST) is associated with symptoms and ventricular arrhythmias.

View Article and Find Full Text PDF

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an uncommon inherited arrhythmia disorder characterized by adrenergically evoked ventricular arrhythmias. Mutations in the cardiac calcium release channel/ryanodine receptor gene (RYR2) are identified in the majority of patients with CPVT. RyR2 is also the major RyR isoform expressed in the brain.

View Article and Find Full Text PDF

Background: Although ventricular fibromas are rare, they are the second most common type of cardiac tumor in children. While histologically benign, they have a propensity to cause malignant arrhythmias, with cardiac arrest often being the first presentation.

Objective: The purpose of this study was to evaluate the arrhythmia risk and management strategies for pediatric ventricular fibromas.

View Article and Find Full Text PDF

Objective: Ivabradine is a selective and specific inhibitor of the I(f) current in the sinoatrial and atrioventricular nodes. It decreases heart rate and myocardial oxygen consumption at rest and during exercise. It is used in adults for management of heart failure and angina, but promising results have been obtained in postural orthostatic tachycardia syndrome (POTS).

View Article and Find Full Text PDF

Background: Sudden arrhythmic death syndrome (SADS) describes a sudden death with negative autopsy and toxicological analysis. Cardiac genetic disease is a likely etiology.

Objectives: This study investigated the clinical utility and combined yield of post-mortem genetic testing (molecular autopsy) in cases of SADS and comprehensive clinical evaluation of surviving relatives.

View Article and Find Full Text PDF

Variants in which encodes a structural component of complex I of the mitochondrial respiratory chain (MRC), were recently independently reported to cause histiocytoid cardiomyopathy (histiocytoid CM) and microphthalmia with linear skin defects syndrome (MLS syndrome). Here we report an additional case of histiocytoid CM, which carries a de novo nonsense variant in (ENST00000276062.8: c.

View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_session43726b18i0ec5eagc2nen2he751ckr41): Failed to open stream: No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 177

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)

Filename: Session/Session.php

Line Number: 137

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once