ERN GUARD-Heart

Generation and Functional Characterization of Cadaver-Derived iPSC-Cardiomyocytes: A Feasibility Study Toward Functional Molecular Autopsy in Sudden Cardiac Death

Sudden cardiac death (SCD) accounts for a substantial share of deaths in young individuals. Despite postmortem pathological, toxicological, and forensic examination and molecular autopsy, many cases remain unexplained, highlighting the need for complementary approaches to investi...

Targeted DNA Sequencing Reveals Distinct Rare-Variant Profiles in Pulmonary Hypertension Associated with Chronic Lung Diseases

The mechanisms underlying the development and severity of pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) remain poorly understood. To investigate the contribution of genetic factors, we performed targeted sequencing...

Brugada Syndrome in the Pediatric Population: Diagnostic Challenges and Clinical Outcome—Results of the German Multicenter Study COGIA

ABSTRACT Introduction Diagnosis and treatment of children and adolescents with suspected Brugada syndrome (BrS) is challenging. Aim of the study was to evaluate the applicability of current diagnostic criteria for pediatric patients with suspected BrS in the German multicenter st...

Treating a Disorder Caused by an Overactive Enzyme: BCKD‐Kinase Deficiency

ABSTRACT Branched‐chain ketoacid dehydrogenase kinase (BCKDK) deficiency is a rare autosomal recessive disorder. Loss of this kinase leaves the branched‐chain α‐ketoacid dehydrogenase complex constitutively active, leading to depletion of branched‐chain amino acids (BCAAs) rather...

Antiarrhythmic Drug Therapy in Cardiomyopathies: A Comparative Synthesis of Guidelines and Consensus Documents

Abstract Purpose of Review Antiarrhythmic drug therapy in cardiomyopathies remains challenging because arrhythmic risk, drug efficacy, and pro-arrhythmic vulnerability vary substantially across phenotypes. This review summarizes contemporary guideline and consensus recommendation...

Incidence, prevalence, and ketoacidosis at onset of type 1 diabetes in Spain: a systematic review and critical assessment of the available evidence

The incidence, prevalence and onset of type 1 diabetes (T1D) with diabetic ketoacidosis (DKA) in Spain remain insufficiently characterized, despite multiple regional analyses. This study aims to summarize and critically assess epidemiologic data in Spain, incorporating insights f...

The Dutch cardiomyopathy registry (DCR); rationale and registry design

BACKGROUND: Cardiomyopathies are important causes of arrhythmias, sudden cardiac death, and heart failure. With accumulating knowledge in clinical, genetic, and molecular phenotyping, the number of distinct disease entities is growing. There is a need for broad, inclusive, high-q...

An N-terminal CDC42 T43I variant reveals the mechanism of pyrin inflammasome activation

Heterozygous carboxyl-terminal variants in the RHO guanosine triphosphatase (GTPase) CDC42 are known to cause severe autoinflammatory syndromes. Here, we identified a heterozygous amino-terminal p.T43I (Thr 43 →Ile) CDC42 variant in patients with autoinflammation and uncovered a...