Enhancing Arrhythmogenic Right Ventricular Cardiomyopathy Detection and Risk Stratification: Insights from Advanced Echocardiographic Techniques.

INTRODUCTION: The echocardiographic diagnosis criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC) are highly specific but sensitivity is low, especially in the early stages of the disease. The role of echocardiographic strain in ARVC has not been fully elucidated, although prior studies suggest that it can improve the detection of subtle functional abnormalities. The purposes of the study were to determine whether these advanced measures of right ventricular (RV) dysfunction on echocardiogram, including RV strain, increase diagnostic value for ARVC disease detection and to evaluate the association of echocardiographic parameters with arrhythmic outcomes. METHODS: The study included 28 patients from the Heart Institute of São Paulo ARVC cohort with a definite diagnosis of ARVC established according to the 2010 Task Force Criteria. All patients were submitted to ECHO's advanced techniques including RV strain, and the parameters were compared to prior conventional visual ECHO and CMR. RESULTS: In total, 28 patients were enrolled in order to perform ECHO's advanced techniques. A total of 2/28 (7%) patients died due to a cardiovascular cause, 2/28 (7%) underwent heart transplantation, and 14/28 (50%) patients developed sustained ventricular arrhythmic events. Among ECHO's parameters, RV dilatation, measured by RVDd (p = 0.018) and RVOT PSAX (p = 0.044), was significantly associated with arrhythmic outcomes. RV free wall longitudinal strain < 14.35% in absolute value was associated with arrhythmic outcomes (p = 0.033). CONCLUSION: Our data suggest that ECHO's advanced techniques improve ARVC detection and that abnormal RV strain can be associated with arrhythmic risk stratification. Further studies are necessary to better demonstrate these findings and contribute to risk stratification in ARVC, in addition to other well-known risk markers.

Challenges and Applications of Genetic Testing in Dilated Cardiomyopathy: Genotype, Phenotype and Clinical Implications. / Desafios e Aplicações dos Testes Genéticos na Cardiomiopatia Dilatada: Genótipo, Fenótipo e Implicações Clínicas.

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.

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.

Evaluation of a new treadmill exercise protocol to unmask type 1 Brugada electrocardiographic pattern: can we improve diagnostic yield?

AIMS: High precordial leads (HPL) on the resting electrocardiogram (ECG) are widely used to improve diagnostic detection of type 1 Brugada ECG pattern (Br1ECGp). A parasympathetic activation marks the initial recovery phase of treadmill stress testing (TET), and this can be useful for detecting the typical ECG pattern. Our study aimed to evaluate the role of a new HPL-treadmill exercise testing (TET) protocol in detecting Br1ECGp fluctuation compared to resting HPL-ECG. METHODS AND RESULTS: 74 out of 163 patients of a Brugada syndrome (BrS) Brazilian cohort (GenBra Registry) underwent exercise testing with HPL-TET protocol. Precordial leads were displayed in strategic positions in the right and left parasternal spaces. The step-by-step analysis included ECG classification (as presence or absence of Br1ECGp) in standard vs. HPL leads placement in the following sequences: resting phase, maximal exercise, and the passive recovery phase (including 'quick lay down'). For heart rate recovery (HRR) measurements and comparisons, a Student's t-test was applied. McNemar tests compared the detection of Br1ECGp. The significance level was defined as P < 0.05. Fifty-seven patients (57/74; 77%) were male, the mean age was 49.0 ± 14, 78.4% had spontaneous BrS, and the mean Shanghai score was 4.5. The HPL-TET protocol increased Br1ECGp detection by 32.4% against resting HPL-ECG (52.7% vs. 20.3%, P = 0.001) alone. CONCLUSION: Stress testing using HPL with the passive recovery phase in the supine position offers an opportunity to unmask the type 1 Br1ECGp, which could increase the diagnostic yield in this population.

Clinical Features, Genetic Findings, and Risk Stratification in Arrhythmogenic Right Ventricular Cardiomyopathy: Data From a Brazilian Cohort.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC), a rare inherited disease, causes ventricular tachycardia, sudden cardiac death, and heart failure (HF). We investigated ARVC clinical features, genetic findings, natural history, and the occurrence of life-threatening arrhythmic events (LTAEs), HF death, or heart transplantation (HF-death/HTx) to identify risk factors. METHODS: The clinical course of 111 consecutive patients with definite ARVC, predictors of LTAE, HF-death/HTx, and combined events were analyzed in the entire cohort and in a subgroup of 40 patients without sustained ventricular arrhythmia before diagnosis. RESULTS: The 5-year cumulative probability of LTAE was 30% and HF-death/HTx was 10%. Predictors of HF-death/HTx were reduced right ventricle ejection fraction (HR: 0.93; P=0.010), HF symptoms (HR: 4.37; P=0.010), epsilon wave (HR: 4.99; P=0.015), and number of leads with low QRS voltage (HR: 1.28; P=0.001). Each additional lead with low QRS voltage increased the risk of HF-death/HTx by 28%. Predictors of LTAE were prior syncope (HR: 1.81; P=0.040), number of leads with T wave inversion (HR: 1.17; P=0.039), low QRS voltage (HR: 1.12; P=0.021), younger age (HR: 0.97; P=0.006), and prior ventricular arrhythmia/ventricular fibrillation (HR: 2.45; P=0.012). Each additional lead with low QRS voltage increased the risk of LTAE by 17%. In patients without ventricular arrhythmia before clinical diagnosis of ARVC, the number of leads with low QRS voltage (HR: 1.68; P=0.023) was independently associated with HF-death/HTx. CONCLUSIONS: Our study demonstrated the characteristics of a specific cohort with a high prevalence of arrhythmic burden at presentation, male predominance, younger age and HF severe outcomes. Our main results suggest that the presence and extension of low QRS voltage can be a risk predictor for HF-death/HTx in ARVC patients, regardless of the arrhythmic risk. This study can contribute to the global ARVC risk stratification, adding new insights to the international current scientific knowledge.

Favorable Safety Experience of Local Dental Anesthesia in ICD Recipients with Cardiac Channelopathies

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.

Desafios e Aplicações dos Testes Genéticos na Cardiomiopatia Dilatada: Genótipo, Fenótipo e Implicações Clínicas / Challenges and Applications of Genetic Testing in Dilated Cardiomyopathy: Genotype, Phenotype and Clinical Implications

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.

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.

Trombo Atrial Esquerdo e Contraste Espontâneo Denso no Uso de Anticoagulante Oral de Ação Direta em Fibrilação Atrial: Visão de Centro Referenciado / Left Atrial Thrombus and Dense Spontaneous Contrast in Direct Oral Anticoagulant Therapy of Atrial Fibrillation: Insights from a Reference Center

Resumo Fundamento No tratamento da fibrilação atrial (FA), a arritmia sustentada mais frequente, com ablação por cateter (ABL) ou cardioversão elétrica (CVE), o período periprocedimento é uma das fases mais críticas. Atualmente, o uso de novos anticoagulantes orais de ação direta (DOAC) é cada vez mais frequente, no entanto, no mundo real, ainda existem poucos dados de estudos sobre a incidência de trombo no átrio esquerdo (TrAE) ou contraste espontâneo denso (CE) no ecocardiograma transesofágico (ETE). Objetivo Analisar a prevalência de TrAE, por ETE, em pacientes em uso de DOAC submetidos à CVE/ABL. Secundariamente: avaliar a associação de comorbidades com a presença de trombos e CE. Métodos Estudo de coorte retrospectivo, unicêntrico, com pacientes do Ambulatório de Arritmia (InCor-HCFMUSP). Foram selecionados e analisados dados clínicos e ecocardiográficos no prontuário da instituição de pacientes com indicação de procedimentos e em uso de DOACs. Considerado um nível de significância de 5%. Resultados Foram incluídos 354 pacientes, no total de 400 procedimentos, de março de 2012-março de 2018. TrAE foi encontrado em 11 pacientes (2,8%), associado com idade avançada (p=0,007) e CHA2DS2-VASc maior (p<0,001). Foi encontrado CE no AE no procedimento antes da ETE em 29 pacientes (7,3%), com menor FEVE (p <0,038) e maior dimensão do AE (p <0,0001). Conclusão A incidência de TrAE e CE em pacientes em uso de DOAC no contexto de CVE/ABL de FA, embora pequena, não é desprezível. Pacientes com escore CHA2DS2-VASc maior, principalmente mais idosos e com diâmetro do AE maior, são mais propensos a esses achados ecocardiográficos.

Abstract Background In the treatment of atrial fibrillation (AF), the most frequently sustained arrhythmia, with catheter ablation (CA) or electrical cardioversion (ECV), the periprocedural period is one of the most critical phases. Currently, the use of new direct action oral anticoagulants (DOAC) is increasingly frequent; however, in the real world, there are still few data on studies on the thrombus incidence in the left atrium (TrLA) or dense spontaneous contrast (DSC) on transesophageal echocardiogram (TEE). Objective To evaluate the prevalence of events and association with risk factors in patients using DOACs. Primary objective: to analyze the prevalence of thrombus in the LA by TEE in patients using DOAC undergoing ECV/CA. Second, evaluate the association of comorbidities with the presence of thrombi and DSC. Methods Retrospective cohort, single-center study with patients followed at the Arrhythmia Outpatient Unit (InCor-HCFMUSP). Patients indicated for procedures and using DOACs were selected, and their clinical/echocardiographic data were analyzed. A significance level of 5% was considered. Results 354 patients were included, a total of 400 procedures, from March 2012-March 2018. Thrombus in the LA was found in 11 patients (2.8%), associated with advanced age (p=0.007) and higher CHA2DS2-VASc (p<0.001) score. DSC in the LA before TEE was found in 29 patients (7.3%), with lower LVEF (p<0.038) and greater LA dimension (p<0.0001). Conclusion The incidence of LA thrombus and DSC in patients using DOC in the context of AF ECV/CA, although small, is not negligible. Patients with higher CHA2DS2-VASc scores, especially older and with larger LA diameter, are more prone to these echocardiographic findings.

Left Atrial Thrombus and Dense Spontaneous Contrast in Direct Oral Anticoagulant Therapy of Atrial Fibrillation: Insights from a Reference Center. / Trombo Atrial Esquerdo e Contraste Espontâneo Denso no Uso de Anticoagulante Oral de Ação Direta em Fibrilação Atrial: Visão de Centro Referenciado.

BACKGROUND: In the treatment of atrial fibrillation (AF), the most frequently sustained arrhythmia, with catheter ablation (CA) or electrical cardioversion (ECV), the periprocedural period is one of the most critical phases. Currently, the use of new direct action oral anticoagulants (DOAC) is increasingly frequent; however, in the real world, there are still few data on studies on the thrombus incidence in the left atrium (TrLA) or dense spontaneous contrast (DSC) on transesophageal echocardiogram (TEE). OBJECTIVE: To evaluate the prevalence of events and association with risk factors in patients using DOACs. Primary objective: to analyze the prevalence of thrombus in the LA by TEE in patients using DOAC undergoing ECV/CA. Second, evaluate the association of comorbidities with the presence of thrombi and DSC. METHODS: Retrospective cohort, single-center study with patients followed at the Arrhythmia Outpatient Unit (InCor-HCFMUSP). Patients indicated for procedures and using DOACs were selected, and their clinical/echocardiographic data were analyzed. A significance level of 5% was considered. RESULTS: 354 patients were included, a total of 400 procedures, from March 2012-March 2018. Thrombus in the LA was found in 11 patients (2.8%), associated with advanced age (p=0.007) and higher CHA2DS2-VASc (p<0.001) score. DSC in the LA before TEE was found in 29 patients (7.3%), with lower LVEF (p<0.038) and greater LA dimension (p<0.0001). CONCLUSION: The incidence of LA thrombus and DSC in patients using DOC in the context of AF ECV/CA, although small, is not negligible. Patients with higher CHA2DS2-VASc scores, especially older and with larger LA diameter, are more prone to these echocardiographic findings.

FUNDAMENTO: No tratamento da fibrilação atrial (FA), a arritmia sustentada mais frequente, com ablação por cateter (ABL) ou cardioversão elétrica (CVE), o período periprocedimento é uma das fases mais críticas. Atualmente, o uso de novos anticoagulantes orais de ação direta (DOAC) é cada vez mais frequente, no entanto, no mundo real, ainda existem poucos dados de estudos sobre a incidência de trombo no átrio esquerdo (TrAE) ou contraste espontâneo denso (CE) no ecocardiograma transesofágico (ETE). OBJETIVO: Analisar a prevalência de TrAE, por ETE, em pacientes em uso de DOAC submetidos à CVE/ABL. Secundariamente: avaliar a associação de comorbidades com a presença de trombos e CE. MÉTODOS: Estudo de coorte retrospectivo, unicêntrico, com pacientes do Ambulatório de Arritmia (InCor-HCFMUSP). Foram selecionados e analisados dados clínicos e ecocardiográficos no prontuário da instituição de pacientes com indicação de procedimentos e em uso de DOACs. Considerado um nível de significância de 5%. RESULTADOS: Foram incluídos 354 pacientes, no total de 400 procedimentos, de março de 2012-março de 2018. TrAE foi encontrado em 11 pacientes (2,8%), associado com idade avançada (p=0,007) e CHA2DS2-VASc maior (p<0,001). Foi encontrado CE no AE no procedimento antes da ETE em 29 pacientes (7,3%), com menor FEVE (p <0,038) e maior dimensão do AE (p <0,0001). CONCLUSÃO: A incidência de TrAE e CE em pacientes em uso de DOAC no contexto de CVE/ABL de FA, embora pequena, não é desprezível. Pacientes com escore CHA2DS2-VASc maior, principalmente mais idosos e com diâmetro do AE maior, são mais propensos a esses achados ecocardiográficos.

Effect of Occurrence of Lamin A/C (LMNA) Genetic Variants in a Cohort of 101 Consecutive Apparent "Lone AF" Patients: Results and Insights.

Objective: Mutations in the Lamin A/C (LMNA) gene are commonly associated with cardiac manifestations, such as dilated cardiomyopathy (DCM) and conduction system disease. However, the overall spectrum and penetrance of rare LMNA variants are unknown. The present study described the presence of LMNA variants in patients with "lone atrial fibrillation (AF)" as their sole clinical presentation. Methods: One-hundred and one consecutive patients with "lone AF" criteria were initially screened by genetic testing. Genetic variants were classified according to the American College of Genetic and Genomic criteria. All subjects were evaluated through clinical and familial history, ECG, 24-h Holter monitoring, echocardiogram, cardiac magnetic resonance, treatment response, and the present relatives of LMNA carriers. In addition, whole-exome data from 49,960 UK Biobank (UKB) participants were analyzed to describe the overall penetrance of rare LMNA missense and loss of function (LOF) variants. Results: Three missense variants in LMNA were identified in probands with AF as their first and unique clinical manifestation. Other five first-degree relatives, after the screening, also presented LMNA gene variants. Among 49,960 analyzed UKB participants, 331 carried rare LMNA missense or LOF variant. Participants who carried a rare LMNA variant were significantly associated with higher odds of arrhythmic events and of an abnormal ECG in the per-protocol ECG exam (p = 0.03 and p = 0.05, respectively). Conclusion: Although a rare occurrence, our findings emphasize the possibility of an initial presentation of apparently "lone AF" in LMNA gene variant carriers.

Peculiar Aspects of Patients with Inherited Arrhythmias during the COVID-19 Pandemic. / Peculiaridade dos Pacientes com Arritmias Hereditárias na Pandemia pela COVID-19.

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.

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.

Peculiaridade dos pacientes com arritmias hereditárias na pandemia pela COVID-19 / Peculiar aspects of patients with Inherited arrhythmias during the COVID-19 pandemic

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.

Impact of adherence to warfarin therapy during 12 weeks of pharmaceutical care in patients with poor time in the therapeutic range.

Poor adherence to warfarin treatment is a contributor to poor quality of treatment, which increases the risk of bleeding and thromboembolic events. This study aims to evaluate the impact of adherence to warfarin therapy on anticoagulation quality during 12 weeks of pharmaceutical care and after 1 year of follow-up for patients with atrial fibrillation and with poor TTR. The Arrhythmia Unit of tertiary hospital in Brazil. We included 262 patients with AF and poor quality of anticoagulation therapy with warfarin (TTR < 50%). Pharmacist-driven therapy management was performed for 12 weeks and patients were also evaluated 1 year after the end of the follow-up with a pharmacist. Adherence was classified into high adherence, medium adherence and low adherence. Impact of adherence to warfarin therapy after pharmaceutical care. Of the 262 patients, 160 were high adherence, 71 were medium adherence and 31 were low adherence. No statistically significant difference is found between adherence groups in demographic and clinical variables. The TTR basal means were not different among adherence groups (p = 0.386). However, the means of TTR 12 weeks and TTR 1 year after the end of protocol were statistically different among adherence groups (p < 0.001 and p = 0.002, respectively). When we compared TTR values at different times within the adherence group, we observed that there is a statistical difference between the three TTR means (basal versus 12 weeks versus 1 year after) within the adherence group (p < 0.001). Patients with poor anticoagulation control, who adhered to the treatment with warfarin during the pharmaceutical care had better anticoagulation quality compared to those who did not adhere to the therapy with warfarin.

Low rate of life-threatening events and limitations in predicting invasive and noninvasive markers of symptoms in a cohort of type 1 Brugada syndrome patients: Data and insights from the GenBra registry.

BACKGROUND: Brugada syndrome (BrS) has diagnostic challenges and controversial risk assessment. We aimed to investigate invasive and noninvasive parameters in symptomatic and asymptomatic patients from a Brazilian cohort of type-1 BrS. METHODS: Patients with spontaneous and drug-induced type-1 BrS were classified into two groups, asymptomatic (n = 116, 84.1%) and symptomatic (n = 22, 15.9%; 13 with arrhythmogenic syncope, 9 with aborted sudden cardiac death). Genetic testing, EPS parameters, and electrocardiogram (ECG) parameters were analyzed. RESULTS: A total of 138 consecutive patients were eligible, 101 men (73.2%), mean 41.4 years, mostly probands (79%). Spontaneous pattern, observed in 77.5% of the patients, was associated with symptoms only if expressed in V1 and V2 standard position (not high precordial leads; p = .014). All symptomatic patients were probands. The presence of right ventricular outflow tract conduction delay (RVOTcd) signs, positive EPS, and SCN5A status was similar between symptomatic and asymptomatic subjects. During the mean 75-month follow-up, eight patients had appropriate therapies. All had spontaneous type-1 ECG pattern and 2/8 (25%) were asymptomatic, with positive EPS. The overall LAE incidence of 1.1% per year dropped to 0.27% in asymptomatic patients. RVOTcd occurred more frequently in SCN5A carriers (QRS-f 33.3% vs. 7.7%; p = .005, AVR sign 58.3% vs. 13.6%; p < .001; deep S in lead I 75% vs. 48.5%, p = .025%), as well as longer HV interval (66 vs. 49 ms; p < .001). CONCLUSIONS: Spontaneous type-1 Brugada pattern in standard leads and proband status were more frequent in symptomatic subjects. RVOTcd, more common in SCN5A carriers, did not predict symptoms in BrS patients. EPS exhibited limited prognostic value for this low-risk population.

Evaluation of the Long-Term Impact on Quality After the End of Pharmacist-Driven Warfarin Therapy Management in Patients With Poor Quality of Anticoagulation Therapy.

BACKGROUND: Warfarin is the most common oral anticoagulant drug, especially in low-income and emerging countries, because of the high cost of direct oral anticoagulant (DOACs), or when warfarin is the only proven therapy (mechanical prosthetic valve and kidney dysfunction). The quality of warfarin therapy is directly associated with dose management. Evidence shows that pharmaceutical care achieves a better quality of therapy with warfarin. However, there are no studies showing this intervention in a specific patient group with poor quality of anticoagulation in a long period after the end of the follow-up by a pharmacist. Thus, the aim of this study was to evaluate whether the quality of warfarin therapy driven by a pharmacist remains stable in the long term after the end of follow up with a pharmacist, in AF patients with poor quality of anticoagulation. METHODS: This is a prospective study, which evaluated about 2,620 patients and selected 262 patients with AF and poor quality of anticoagulation therapy with warfarin (TTR<50% - based on the last three values of international normalized ratio). Pharmacist-driven therapy management was performed up to 12 weeks. Data from patients were evaluated 1 year after the end of the follow-up with pharmacist. RESULTS: Comparison between mean TTR after 12 weeks of pharmaceutical care (54.1%) and mean TTR one year after the end of the pharmaceutical care (56.5%; p=0.081) did not achieve statistical difference, demonstrating that the increment of quality due to intervention of 12 weeks was maintained for 1 year after intervention. CONCLUSION: The long-term impact of pharmaceutical care was beneficial for patients with AF and poor quality of warfarin anticoagulation. This design might be an important strategy to treat a subgroup of patients without proven effectiveness of warfarin.

Natural History and Risk Stratification in Andersen-Tawil Syndrome Type 1.

BACKGROUND: Andersen-Tawil Syndrome type 1 (ATS1) is a rare arrhythmogenic disorder, caused by loss-of-function mutations in the KCNJ2 gene. We present here the largest cohort of patients with ATS1 with outcome data reported. OBJECTIVES: This study sought to define the risk of life-threatening arrhythmic events (LAE), identify predictors of such events, and define the efficacy of antiarrhythmic therapy in patients with ATS1. METHODS: Clinical and genetic data from consecutive patients with ATS1 from 23 centers were entered in a database implemented at ICS Maugeri in Pavia, Italy, and pooled for analysis. RESULTS: We enrolled 118 patients with ATS1 from 57 families (age 23 ± 17 years at enrollment). Over a median follow-up of 6.2 years (interquartile range: 2.7 to 16.5 years), 17 patients experienced a first LAE, with a cumulative probability of 7.9% at 5 years. An increased risk of LAE was associated with a history of syncope (hazard ratio [HR]: 4.54; p = 0.02), with the documentation of sustained ventricular tachycardia (HR 9.34; p = 0.001) and with the administration of amiodarone (HR: 268; p < 0.001). The rate of LAE without therapy (1.24 per 100 person-years [py]) was not reduced by beta-blockers alone (1.37 per 100 py; p = 1.00), or in combination with Class Ic antiarrhythmic drugs (1.46 per 100 py, p = 1.00). CONCLUSIONS: Our data demonstrate that the clinical course of patients with ATS1 is characterized by a high rate of LAE. A history of unexplained syncope or of documented sustained ventricular tachycardia is associated with a higher risk of LAE. Amiodarone is proarrhythmic and should be avoided in patients with ATS1.

Is It Safe for Patients With Cardiac Channelopathies to Undergo Routine Dental Care? Experience From a Single-Center Study.

Background Brugada syndrome and long-QT syndrome may account for at least one third of unexplained sudden cardiac deaths. Dental care in patients with cardiac channelopathies is challenging because of the potential risk of life-threatening events. We hypothesized that the use of local dental anesthesia with lidocaine with and without epinephrine is safe and does not result in life-threatening arrhythmias in patients with channelopathies. Methods and Results We performed a randomized, double-blind pilot trial comparing the use of 2% lidocaine without a vasoconstrictor and with 1:100 000 epinephrine in 2 sessions of restorative dental treatment with a washout period of 7 days (crossover trial). Twenty-eight-hour Holter monitoring was performed, and 12-lead electrocardiography, digital sphygmomanometry, and anxiety scale assessments were also conducted at 3 time points. Fifty-six dental procedures were performed in 28 patients (18 women, 10 men) with cardiac channelopathies: 16 (57.1%) had long-QT syndrome, and 12 (42.9%) had Brugada syndrome; 11 (39.3%) of patients had an implantable defibrillator. The mean age was 45.9±15.9 years. The maximum heart rate increased after the use of epinephrine during the anesthesia period from 82.1 to 85.8 beats per minute (P=0.008). In patients with long-QT syndrome, the median corrected QT was higher, from 450.1 to 465.4 ms (P=0.009) at the end of anesthesia in patients in whom epinephrine was used. The other measurements showed no statistically significant differences. No life-threatening arrhythmias occurred during dental treatment. Conclusions The use of local dental anesthesia with lidocaine, regardless of the use of a vasoconstrictor, did not result in life-threatening arrhythmias and appears to be safe in stable patients with cardiac channelopathies. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03182777.

Pharmaceutical Care Increases Time in Therapeutic Range of Patients With Poor Quality of Anticoagulation With Warfarin.

Thromboembolic events are associated with high mortality and morbidity indexes. In this context, warfarin is the most widely prescribed oral anticoagulant agent for preventing and treating these events. This medication has a narrow therapeutic range and, consequently, patients usually have difficulty in achieving and maintaining stable target therapeutics. Some studies on the literature about oral anticoagulant management showed that pharmacists could improve the efficiency of anticoagulant therapy. However, the majority of these studies included general patients retrospectively. The aim of this study was to prospectively evaluate a pharmacist's warfarin management in patients with poor quality of anticoagulation therapy (Time in the Therapeutic Range- TTR < 50%). We included 268 patients with atrial fibrillation (AF) and without stable dose of warfarin (TTR < 50%, based on the last three values of International Normalized Ratio-INR). We followed them up for 12 weeks, INR values were evaluated and, when necessary, the dose adjustments were performed. During the first four visits, patient's INR was measured every 7 days. Then, if INR was within the target therapeutic range (INR: 2-3), the patient was asked to return in 30 days. However, if INR was out the therapeutic target, the patient was asked to return in 7 days. Adherence evaluation was measured through questionnaires and by counting the pills taken. Comparison between basal TTR (which was calculated based on the three last INR values before prospective phase) and TTR of 4 weeks (calculated by considering the INR tests from visits 0 to 4, in the prospective phase of the study) and basal TTR and TTR of 12 weeks (calculated based on the INR tests from visits 0 to 12, in the prospective phase of the study) revealed significant statistical differences (0.144 ± 0.010 vs. 0.382 ± 0.016; and 0.144 ± 0.010 vs. 0.543 ± 0.014, p < 0.001, respectively). We also observed that the mean TTR of 1 year before (retrospective phase) was lower than TTR value after 12 weeks of pharmacist-driven treatment (prospective phase) (0.320 ± 0.015; 0.540 ± 0.015, p < 0.001). In conclusion, pharmaceutical care was able to improve TTR values in patients with AF and poor quality of anticoagulation with warfarin.