Abstract Cardiomyopathy is characterized by structural and functional abnormalities in the heart muscle that are not influenced by coronary disease, hypertension, valve disease, or congenital heart defects. Genetic testing, which helps diagnose the molecular bases of cardiomyopathy, can affect prognostication and clinical decisions. Recent guidelines advocate classifying cardiomyopathies based on phenotypic categories, which encompass a range of clinical presentations, underlying causes, and outcomes. Beyond deepening our grasp of the disease, genetic testing can distinguish between diseases with similar presentations, known as genocopies, which can profoundly influence treatment decisions. Genetic testing is also essential for reproductive counseling and risk evaluation among family members. Combined with advanced imaging techniques such as magnetic resonance imaging, genetic investigation offers a comprehensive understanding of the disease. Thus, as the nature of cardiomyopathies continues to be unraveled, cardiologists must stay updated on advances in genetic testing and their practical applications. disease hypertension defects cardiomyopathy decisions categories presentations causes outcomes genocopies members Thus unraveled applications

Abstract Background Dental anesthetic management in implantable cardioverter defibrillator (ICD) recipients with cardiac channelopathies (CCh) can be challenging due to the potential risk of life-threatening arrhythmias and appropriate ICD therapies during procedural time. Objectives The present study assessed the hypothesis that the use of local dental anesthesia with 2% lidocaine with 1:100,000 epinephrine or without a vasoconstrictor can be safe in selected ICD and CCh patients, not resulting in life-threatening events (LTE). Methods Restorative dental treatment under local dental anesthesia was made in two sessions, with a wash-out period of 7 days (cross-over trial), conducting with a 28h - Holter monitoring, and 12-lead electrocardiography, digital sphygmomanometry, and anxiety scale assessments in 3 time periods. Statistical analysis carried out the paired Student’s t test and the Wilcoxon signed-rank test. In all cases, a significance level of 5% was adopted. All patients were in stable condition with no recent events before dental care. Results Twenty-four consecutive procedures were performed in 12 patients (9 women, 3 men) with CCh and ICD: 7 (58.3%) had long QT syndrome (LQTS), 4 (33.3%) Brugada syndrome (BrS), and 1 (8.3%) Catecholaminergic polymorphic ventricular tachycardia (CPVT). Holter analysis showed no increased heart rate (HR) or sustained arrhythmias. Blood pressure (BP), electrocardiographic changes and anxiety measurement showed no statistically significant differences. No LTE occurred during dental treatment, regardless of the type of anesthesia. Conclusion Lidocaine administration, with or without epinephrine, can be safely used in selected CCh-ICD patients without LTE. These preliminary findings need to be confirmed in a larger population with ICD and CCh. (ICD (CCh lifethreatening life threatening 2 1100,000 1100000 100,000 100 000 1:100,00 . (LTE) sessions washout wash crossover cross over trial, trial , trial) h monitoring 12lead lead electrocardiography sphygmomanometry periods Students Student s signedrank signed rank cases 5 adopted care Twentyfour Twenty four 9 ( women men 58.3% 583 58 (58.3% LQTS, LQTS (LQTS) 33.3% 333 33 (33.3% BrS, BrS (BrS) 8.3% 83 8 (8.3% CPVT. CPVT (CPVT) HR (HR BP, BP (BP) differences administration CChICD 1100 1100,00 110000 100000 100,00 10 00 1:100,0 (LTE 58.3 (58.3 (LQTS 33.3 (33.3 (BrS 8.3 (8.3 (CPVT (BP 110 1100,0 11000 10000 100,0 0 1:100, 58. (58. 33. (33. 8. (8. 11 1100, 1000 100, 1:100 (58 (33 (8 1:10 (5 (3 1:1 1:

Resumo Os testes genéticos para cardiomiopatia dilatada (CMD) apresentam uma positividade de até 40%, mas há uma grande heterogeneidade genética e outros desafios decorrentes de expressividade variável e penetrância incompleta. O heredograma é fundamental para diferenciar os casos de CMD esporádica e familiar, por meio da avaliação do histórico familiar. A CMD familiar apresenta um rendimento maior nos testes genéticos, mas a CMD esporádica não exclui a possibilidade de causa genética. Alguns genes têm fenótipos específicos, sendo o gene da Lamina ( LMNA ) o mais fortemente associado a um fenótipo de arritmias malignas e quadros de insuficiência cardíaca (IC) avançada. A presença de uma variante genética causal também pode ajudar na avaliação prognóstica, identificando quadros mais graves e com menores taxas de remodelamento reverso em comparação com indivíduos com genótipo negativo. As diretrizes atuais recomendam a avaliação e aconselhamento genético em indivíduos com CMD, além do rastreamento em cascata nos familiares de primeiro grau nos casos em que há uma ou mais variantes identificadas, sendo uma oportunidade para o diagnóstico e tratamento precoces. Familiares com genótipo positivo e fenótipo negativo são candidatos à avaliação seriada, com periodicidade que varia conforme a idade. O genótipo também auxilia na indicação individualizada de cardiodesfibrilador implantável e em recomendações quanto à atividade física e planejamento familiar. Estudos em curso esclarecem progressivamente os detalhes das relações genótipo/fenótipo de um grande número de variantes e fazem com que a genética molecular esteja cada vez mais presente na prática clínica. (CMD 40 40% incompleta específicos IC (IC avançada prognóstica identificadas precoces seriada idade genótipofenótipo clínica 4

Abstract Genetic tests for dilated cardiomyopathy (DCM) have a diagnostic yield of up to 40%, but there is significant genetic heterogeneity and other challenges, such as variable expressivity and incomplete penetrance. Pedigree analysis is essential for distinguishing between sporadic and familial DCM cases by assessing family history. Familial DCM yields higher results in genetic testing, but sporadic DCM does not rule out the possibility of a genetic cause. Some genes have specific phenotypes, with the Lamin gene ( LMNA ) being associated with a phenotype of malignant arrhythmias and advanced heart failure (HF). The presence of a causal genetic variant can also aid in prognostic evaluation, identifying more severe cases with lower rates of reverse remodeling (RR) compared to individuals with a negative genotype. Current guidelines recommend genetic evaluation and counseling for individuals with DCM, along with cascade screening in first-degree relatives in cases where one or more variants are identified, offering an opportunity for early diagnosis and treatment. Relatives with a positive genotype and negative phenotype are candidates for serial evaluation, with frequency varying by age. Genotype also assists in individualized recommendations for implantable cardioverter-defibrillator (ICD) placement and advice regarding physical activity and family planning. Ongoing studies are progressively elucidating the details of genotype/phenotype relationships for a large number of variants, making molecular genetics increasingly integrated into clinical practice. (DCM 40 40% challenges penetrance history testing cause phenotypes HF. HF . (HF) RR (RR firstdegree first degree identified treatment age cardioverterdefibrillator cardioverter defibrillator ICD (ICD planning genotypephenotype practice 4 (HF

Resumo Desde dezembro de 2019, observamos o rápido avanço da síndrome respiratória aguda grave causada pelo coronavírus 2019 (SARS-CoV-2). O impacto da evolução clínica de uma infecção respiratória é pouco conhecido em pacientes portadores de arritmias hereditárias, devido à baixa prevalência dessas doenças. Os pacientes que apresentam quadros infecciosos podem exacerbar arritmias primárias ocultas ou bem controladas, por diversos fatores, tais como febre, distúrbios eletrolíticos, interações medicamentosas, estresse adrenérgico e, eventualmente, o próprio dano miocárdico do paciente séptico. O objetivo desta revisão é destacar os principais desafios que podemos encontrar durante a pandemia pela Covid 19, especificamente nos pacientes com arritmias hereditárias, com destaque para a síndrome do QT longo congênito (SQTL), a síndrome de Brugada (SBr), a taquicardia ventricular polimórfica catecolaminérgica (TVPC) e a cardiomiopatia arritmogênica do ventrículo direito.

Abstract Since December 2019 we have observed the rapid advance of the severe acute respiratory syndrome caused by the new coronavirus (SARS-CoV-2). The impact of the clinical course of a respiratory infection is little known in patients with hereditary arrhythmias, due to the low prevalence of these diseases. Patients who present with infectious conditions may exacerbate hidden or well-controlled primary arrhythmias, due to several factors, such as fever, electrolyte disturbances, drug interactions, adrenergic stress and, eventually, the septic patient’s own myocardial damage. The aim of this review is to highlight the main challenges we may encounter during the Covid 19 pandemic, specifically in patients with hereditary arrhythmias, with emphasis on the congenital long QT syndrome (LQTS), Brugada syndrome (SBr), ventricular tachycardia polymorphic catecholaminergic (CPVT) and arrhythmogenic right ventricular cardiomyopathy.