Diagnostic Yield of Genetic Testing in Young Patients With Atrioventricular Block of Unknown Cause

BACKGROUND: The cause of atrioventricular block (AVB) remains unknown in approximately half of young patients with the diagnosis. Although variants in several genes associated with cardiac conduction diseases have been identified, the contribution of genetic variants in younger patients with AVB is unknown. METHODS AND RESULTS: Using the Danish Pacemaker and Implantable Cardioverter Defibrillator (ICD) Registry, we identified all patients younger than 50 years receiving a pacemaker because of AVB in Denmark in the period from January 1, 1996 to December 31, 2015. From medical records, we identified patients with unknown cause of AVB at time of pacemaker implantation. These patients were invited to a genetic screening using a panel of 102 genes associated with inherited cardiac diseases. We identified 471 living patients with AVB of unknown cause, of whom 226 (48%) accepted participation. Median age at the time of pacemaker implantation was 39 years (interquartile range, 32–45 years), and 123 (54%) were men. We found pathogenic or likely pathogenic variants in genes associated with or possibly associated with AVB in 12 patients (5%). Most variants were found in the LMNA gene (n=5). LMNA variant carriers all had a family history of either AVB and/or sudden cardiac death. CONCLUSIONS: In young patients with AVB of unknown cause, we found a possible genetic cause in 1 out of 20 participating patients. Variants in the LMNA gene were most common and associated with a family history of AVB and/or sudden cardiac death, suggesting that genetic testing should be a part of the diagnostic workup in these patients to stratify risk and screen family members

Predictors of Fabry disease in patients with hypertrophic cardiomyopathy: how to guide the diagnostic strategy?

Fabry disease (FD) is a treatable cause of hypertrophic cardiomyopathy (HCM). We aimed to determine the independent predictors of FD and to define a clinically useful strategy to discriminate FD among HCM.Shire Human Genetic Therapies, Inc.info:eu-repo/semantics/publishedVersio

Case report: spontaneous coronary artery dissection and suspicion of takotsubo cardiomyopathy in a patient presenting with T-wave inversions, severe QTc prolongation, elevated cardiac biomarkers, and apical akinesia

Abstract Background In patients suspected of acute coronary syndrome, but where the coronary angiography (CAG) has shown unobstructed coronary arteries differential diagnoses include spontaneous coronary artery dissection and takotsubo cardiomyopathy. This case report presents a patient with spontaneous coronary artery dissection but diagnostic signs suspicious of takotsubo cardiomyopathy. Which leads to a consideration of the co-existence of the diseases. Case summary A 57-year-old woman was acutely admitted to the emergency ward with sudden development of chest discomfort, palpitations, and dyspnoea. At hospitalization, the electrocardiography showed T-wave inversions in I, aVL, and V2, and Troponin I was elevated. Initial echocardiography revealed apical akinesia consistent with takotsubo cardiomyopathy. Initially, a diagnosis of acute coronary syndrome or takotsubo cardiomyopathy was suspected. The patient was further diagnostically assessed with CAG including optical coherence tomography which showed spontaneous coronary artery dissection in the left anterior descending artery. At follow-up 3 months later, CAG showed a fully healed coronary artery, and repeated echocardiography showed normalization of the left ventricular function. Discussion In this case report, initially, acute coronary syndrome was suspected due to electrocardiography with T-wave inversions and elevated cardiac biomarkers. Takotsubo cardiomyopathy was suspected when echocardiography showed apical ballooning, but CAG with optical coherence tomography revealed a spontaneous coronary artery dissection. Interestingly no severe obstructions of coronary arteries were seen, and follow-up echocardiography showed fully regained myocardial function. This leads to the debate as to whether this might be a case of co-existing spontaneous coronary artery dissection and takotsubo cardiomyopathy. </jats:sec