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.

Motivos y complicaciones relacionadas con el rechazo de pruebas diagnósticas y recomendaciones terapéuticas en cardiopatías familiares. Estudio RELUCTANT / Reasons for refusing diagnostic tests and therapeutic recommendations and associated complications in inherited heart diseases. The RELUCTANT study

Introducción y objetivos: El estudio de las cardiopatías familiares implica realizar pruebas diagnósticas, a veces molestas, a familiares asintomáticos. El objetivo de este proyecto es cuantificar el rechazo a dichas pruebas y recomendaciones terapéuticas. Métodos: Se evaluó a 1.992 familias consecutivas con cardiopatías familiares para analizar el rechazo al cribado familiar. Se evaluó a 1.539 (recomendación de cardiorresonancia) y 837 (recomendación de test de provocación farmacológica). Se evaluó a 395 pacientes con indicación de desfibrilador automático implantable (DAI) y 402 con indicación de anticoagulación, para estudiar el rechazo de los tratamientos. Resultados: El 28% de las familias a las que se recomienda estudio por sospecha de cardiopatía familiar no acuden; el rechazo es menor si hay antecedentes familiares de muerte súbita. El 23% no se sometió a la resonancia; los 2 motivos más alegados son citación imposible (53%) y claustrofobia (18%). Las personas de más edad, las mujeres, los sintomáticos, los individuos con arritmias y los familiares rechazaron más la prueba. El 19% no se hizo el test de provocación farmacológica por temor (46%) o citación imposible (25%). Los individuos de más edad, los asintomáticos, aquellos con antecedente de arritmias, los familiares y aquellos con estudio genético positivo lo rechazaron en mayor proporción. Solo una minoría de pacientes rechazaron los tratamientos (el 5,1% el DAI y el 2,5% la anticoagulación). La tasa de muerte súbita entre los que rechazaron el DAI fue alta (el 4,5% al año). Conclusiones: Una quinta parte de las personas que acuden al cribado de cardiopatías familiares rechazan la realización de pruebas más sofisticadas y molestas. Se identifican varios predictores independientes asociados con el rechazo. Solo una minoría de pacientes en alto riesgo rechazan los tratamientos como la anticoagulación o el implante de DAI. (AU)

Introduction and objectives: Study of inherited heart diseases (IHD) involves performing diagnostic tests, which are sometimes inconvenient or stressful, in asymptomatic relatives. The aim of this study was to analyze refusal to undergo various diagnostic tests and follow therapeutic recommendations. Methods: We assessed 1992 consecutive families with IHD to analyze refusal to undergo family screening. The study included 1539 individuals who were recommended to undergo cardiac magnetic resonance, and 837 who were recommended a drug challenge test. To study treatment refusal, we assessed 395 patients with an indication for an implantable cardioverter-defibrillator (ICD) and 402 patients with an indication for anticoagulation. Results: A total of 28% of families who were recommended to undergo screening for suspected IHD did not attend, but refusal was lower if there was a family history of sudden cardiac death. In all, 23% did not undergo magnetic resonance, and the 2 main reasons were administrative problems (53%) and claustrophobia (18%). Refusal was more common in older people, women, symptomatic persons, individuals with arrhythmias, and relatives. Nearly one fifth (19%) did not take the drug challenge test, due to fear (46%) or administrative issues (25%). Refusal was more frequent in older individuals, asymptomatic persons, those with a history of arrhythmias, relatives, and those with a positive genetic study. Only a minority of patients rejected the treatments (5.1% ICD, 2.5% anticoagulation). The percentage of sudden cardiac death in persons rejecting ICD implantation was high (4.5% per year). Conclusions: One fifth of people attending screening for IHD refused to undergo more sophisticated and stressful tests. This study identified several independent predictors associated with refusal. Only a minority of high-risk patients refused treatments such as ICD implantation and anticoagulation. (AU)

Reasons for refusing diagnostic tests and therapeutic recommendations and associated complications in inherited heart diseases. The RELUCTANT study.

INTRODUCTION AND OBJECTIVES: Study of inherited heart diseases (IHD) involves performing diagnostic tests, which are sometimes inconvenient or stressful, in asymptomatic relatives. The aim of this study was to analyze refusal to undergo various diagnostic tests and follow therapeutic recommendations. METHODS: We assessed 1992 consecutive families with IHD to analyze refusal to undergo family screening. The study included 1539 individuals who were recommended to undergo cardiac magnetic resonance, and 837 who were recommended a drug challenge test. To study treatment refusal, we assessed 395 patients with an indication for an implantable cardioverter-defibrillator (ICD) and 402 patients with an indication for anticoagulation. RESULTS: A total of 28% of families who were recommended to undergo screening for suspected IHD did not attend, but refusal was lower if there was a family history of sudden cardiac death. In all, 23% did not undergo magnetic resonance, and the 2 main reasons were administrative problems (53%) and claustrophobia (18%). Refusal was more common in older people, women, symptomatic persons, individuals with arrhythmias, and relatives. Nearly one fifth (19%) did not take the drug challenge test, due to fear (46%) or administrative issues (25%). Refusal was more frequent in older individuals, asymptomatic persons, those with a history of arrhythmias, relatives, and those with a positive genetic study. Only a minority of patients rejected the treatments (5.1% ICD, 2.5% anticoagulation). The percentage of sudden cardiac death in persons rejecting ICD implantation was high (4.5% per year). CONCLUSIONS: One fifth of people attending screening for IHD refused to undergo more sophisticated and stressful tests. This study identified several independent predictors associated with refusal. Only a minority of high-risk patients refused treatments such as ICD implantation and anticoagulation.

Genetic Testing in Inherited Heart Diseases.

Inherited heart diseases include numerous conditions, from the more prevalent hypertrophic cardiomyopathy (HCM) and familial hypercholesterolaemia (FH), to the comparatively less common inherited arrhythmia syndromes, such as long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT) and Brugada syndrome (BrS). Genetic testing has evolved rapidly over the last decade and is now considered a mainstream component of clinical management of inherited heart diseases. Cardiac manifestations can also be part of wider syndromes, and genetic testing can play a critical role in clarifying the underlying aetiological basis of disease in some cases. The greatest utility of a genetic diagnosis, however, comes from the ability to elucidate disease risk amongst asymptomatic at-risk family members. Given the nuances and challenges, cardiac genetic testing is best performed in a multidisciplinary specialised clinic with access to cardiac genetic counselling.