PRKAG2 syndrome, a rare hypertrophic cardiomyopathy: a Brazilian long-term follow-up with extracardiac disorders.

OBJECTIVE: This study aimed to provide a long-term follow-up of PRKAG2 syndrome and describe the new phenotypic aspects of the condition. PRKAG2 syndrome is a rare autosomal-dominant glycogen storage disease characterized by cardiac hypertrophy, ventricular pre-excitation, and conduction system disease. Fatal arrhythmias occur frequently. METHODS: A family cohort of 66 participants was recruited. Clinical and genetic analyses were performed. RESULTS: Median age of 36.97±17.28 years, with 69.9% being men. Nineteen subjects carried the deleterious variant p.K290I of the PRKAG2 gene. This group experienced many malignant events, including eight pacemaker implants, three sudden cardiac deaths, five aborted cardiac arrests, four strokes, four premature neonatal deaths, two spontaneous abortions, five forceps deliveries, and 12 cesarean procedures. Extracardiac involvement, such as in neurocognitive and psychiatric disorders, has been observed only in carriers of mutations. Palpitations, Syncope, atrial fibrillation, atrial flutter, sinus pauses, and bradycardia were strongly and significantly associated with major or severe adverse events (sudden cardiac death, aborted cardiac arrest, pacemaker use, stroke, and congestive heart failure). Early diagnosis and intervention through antiarrhythmic drugs, anticoagulation, pacemaker implantation, radiofrequency catheter ablation, and cesarean section surgery improved the symptoms and survival rates. Mutations carriers were advised to avoid pregnancy. CONCLUSION: This study identified that the p.K291I_PRKAG2 mutation is associated with poor prognosis, highlighting the need for early intervention. Further research may uncover the potential connections between intellectual disability, miscarriage, and neonatal death in individuals with this syndrome.

Comparison between cryotherapy and radiofrequency energy sources for parahisian accessory pathway percutaneous ablation.

BACKGROUND: Catheter ablation of parahisian accessory pathways (PHAP) are challenging due to their proximity to the normal conduction system. Retrospective studies suggest that cryoablation has a better safety profile but a higher recurrence rate when compared to radiofrequency ablation (RFCA). The objective of this study was to compare the results of parahisian AP ablation performed by electrophysiologists with experience in both technologies. METHODS: Prospective single-center, non-blinded and 1:1 model was used. Patients included had parahisian AP confirmed by an electrophysiological study and referred for radiofrequency or cryotherapy ablation according to current guidelines, under fluoroscopic guidance. No electroanatomic mapping was used. RESULTS: A total of 30 patients (mean age of 25±9.4 years; 90% male) were enrolled between Oct/2018 to Feb/2020. Acute success rate between RFCA and CRYO were similar (93% vs. 87%, p = 0.54). A nonsignificant reduction in short-term recurrence rate for RFCA (14% vs. 30%, p = 0.3) and mechanical trauma (6% vs. 20%; p = 0.28) was observed. Long-term recurrence rate and event-free survival time were similar in both groups after 1-year follow-up (p = 0.286). No persistent complete AV block or conduction disturbance was also observed. CONCLUSION: Considering the limitation of a small sample size and the lack of use of electroanatomic mapping for RFCA, the efficacy and safety profile of parahisian AP ablation with RFCA was not different from CRYO, when performed by experienced electrophysiologists. No cases of permanent complete AV block were reported with either energy modalities.

PRKAG2 syndrome, a rare hypertrophic cardiomyopathy: a Brazilian long-term follow-up with extracardiac disorders

ABSTRACT Objective This study aimed to provide a long-term follow-up of PRKAG2 syndrome and describe the new phenotypic aspects of the condition. PRKAG2 syndrome is a rare autosomal-dominant glycogen storage disease characterized by cardiac hypertrophy, ventricular pre-excitation, and conduction system disease. Fatal arrhythmias occur frequently. Methods A family cohort of 66 participants was recruited. Clinical and genetic analyses were performed. Results Median age of 36.97±17.28 years, with 69.9% being men. Nineteen subjects carried the deleterious variant p.K290I of the PRKAG2 gene. This group experienced many malignant events, including eight pacemaker implants, three sudden cardiac deaths, five aborted cardiac arrests, four strokes, four premature neonatal deaths, two spontaneous abortions, five forceps deliveries, and 12 cesarean procedures. Extracardiac involvement, such as in neurocognitive and psychiatric disorders, has been observed only in carriers of mutations. Palpitations, Syncope, atrial fibrillation, atrial flutter, sinus pauses, and bradycardia were strongly and significantly associated with major or severe adverse events (sudden cardiac death, aborted cardiac arrest, pacemaker use, stroke, and congestive heart failure). Early diagnosis and intervention through antiarrhythmic drugs, anticoagulation, pacemaker implantation, radiofrequency catheter ablation, and cesarean section surgery improved the symptoms and survival rates. Mutations carriers were advised to avoid pregnancy. Conclusion This study identified that the p.K291I_PRKAG2 mutation is associated with poor prognosis, highlighting the need for early intervention. Further research may uncover the potential connections between intellectual disability, miscarriage, and neonatal death in individuals with this syndrome.

Rivaroxaban versus warfarin in postoperative atrial fibrillation: Cost-effectiveness analysis in a single-center, randomized, and prospective trial.

Objectives: Postoperative atrial fibrillation is the most common clinical complication after coronary artery bypass graft surgery. It is associated with a high risk of both stroke and death and increases the length of hospital stay and costs. This study aimed to evaluate anticoagulants in postoperative atrial fibrillation. Methods: A single-center, randomized, prospective, and open-label study. The trial was conducted in Heart Institute at University of São Paulo, Brazil. Patients who developed postoperative atrial fibrillation were randomized to anticoagulation with rivaroxaban or warfarin plus enoxaparin bridging. The primary objective was the cost-effectiveness evaluated by quality-adjusted life years, using the SF-6D questionnaire. The secondary end point was the combination of death, stroke, myocardial infarction, thromboembolic events, infections, bleeding, readmissions, and surgical reinterventions. The safety end point was any bleeding using the International Society on Thrombosis and Haemostasis score. Follow-up period was 30 days after hospital discharge. Results: We analyzed 324 patients and 53 patients were randomized. The median cost-effectiveness was $1423.20 in the warfarin group versus $586.80 in the rivaroxaban group (P = .002). The median cost was lower in the rivaroxaban group, $450.20 versus $947.30 (P < .001). The secondary outcome was similar in both groups, 44.4% in warfarin group versus 38.5% in the rivaroxaban group (P = .65). Bleeding occured in 25.9% in the warfarin group versus 11.5% in the rivaroxaban group (P = .18). Conclusions: Rivaroxaban was more cost-effective when compared with warfarin associated with enoxaparin bridging in postoperative atrial fibrillation after isolated coronary artery bypass grafting.

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.

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.

Incor Residency Program in Adult Cardiology in 2022: 40 Years Preparing Cardiologists for the Demands in Brazil. / Programa de Residência Médica em Cardiologia de Adultos do InCor em 2022: 40 Anos Formando Cardiologistas para as Demandas do Brasil.

BACKGROUND: Considering demographic data related to the cardiologist's fields of work in Brazil, the administrative board of the InCor medical residency program decided for an update of its curriculum content, to adapt the educational process to the cardiologist's work reality. OBJECTIVE: This article aimed to describe the recent updates applied to the InCor medical residency program. METHODS: In the article, we described the recent updates on the InCor residency program, and compared the current curriculum track with the previous one. We also presented the rationale for these changes, based on the literature on the participation of cardiologists in the labor market. RESULTS: There was a reduction in the working hours of residents in training in the intensive care unit, and an increase in the outpatient activities of primary and secondary prevention. Also, the didactic content was reformulated and became organized by the corresponding division. CONCLUSION: The update of the curriculum track of the InCor medical residency program was required in order to adapt it to the Brazilian labor market. The commission in charge of this update is aware that this is a dynamic process that may need changes over time.

FUNDAMENTO: Diante de dados demográficos referentes às áreas de atuação dos cardiologistas no Brasil, a coordenação do Programa de Residência Médica em Cardiologia do Instituto do Coração (PRM INCOR) entendeu a necessidade de uma atualização de seu conteúdo programático, a fim de adaptar o processo de formação à realidade profissional do cardiologista. OBJETIVO: O presente artigo tem como objetivo descrever à comunidade científica as atualizações recentemente implementadas no PRM INCOR. MÉTODOS: No artigo, descrevemos as atualizações recentes do PRM INCOR, comparando a grade teórica pregressa e a atual. Expomos também o racional por trás de tais mudanças com dados de literatura relacionados à atuação do médico cardiologista no mercado de trabalho. RESULTADO: Houve uma redução da carga horária destinada a estágios de terapia intensiva, e um incremento nas atividades ambulatoriais relacionadas a medidas de prevenção primária e secundária. Além disso, o programa passou por uma reformulação de seu conteúdo didático, organizado agora por núcleos de competência. CONCLUSÃO: A atualização da grade curricular decorre da necessidade de adequar o PRM INCOR à realidade atual do mercado de trabalho brasileiro. O grupo envolvido na atualização está ciente que se trata de um processo dinâmico e que pode exigir modificações no decorrer do tempo.

Programa de Residência Médica em Cardiologia de Adultos do InCor em 2022: 40 Anos Formando Cardiologistas para as Demandas do Brasil / Incor Residency Program in Adult Cardiology in 2022: 40 Years Preparing Cardiologists for the Demands in Brazil

Resumo Fundamento Diante de dados demográficos referentes às áreas de atuação dos cardiologistas no Brasil, a coordenação do Programa de Residência Médica em Cardiologia do Instituto do Coração (PRM INCOR) entendeu a necessidade de uma atualização de seu conteúdo programático, a fim de adaptar o processo de formação à realidade profissional do cardiologista. Objetivo O presente artigo tem como objetivo descrever à comunidade científica as atualizações recentemente implementadas no PRM INCOR. Métodos No artigo, descrevemos as atualizações recentes do PRM INCOR, comparando a grade teórica pregressa e a atual. Expomos também o racional por trás de tais mudanças com dados de literatura relacionados à atuação do médico cardiologista no mercado de trabalho. Resultado Houve uma redução da carga horária destinada a estágios de terapia intensiva, e um incremento nas atividades ambulatoriais relacionadas a medidas de prevenção primária e secundária. Além disso, o programa passou por uma reformulação de seu conteúdo didático, organizado agora por núcleos de competência. Conclusão A atualização da grade curricular decorre da necessidade de adequar o PRM INCOR à realidade atual do mercado de trabalho brasileiro. O grupo envolvido na atualização está ciente que se trata de um processo dinâmico e que pode exigir modificações no decorrer do tempo.

Abstract Background Considering demographic data related to the cardiologist's fields of work in Brazil, the administrative board of the InCor medical residency program decided for an update of its curriculum content, to adapt the educational process to the cardiologist's work reality. Objective This article aimed to describe the recent updates applied to the InCor medical residency program. Methods In the article, we described the recent updates on the InCor residency program, and compared the current curriculum track with the previous one. We also presented the rationale for these changes, based on the literature on the participation of cardiologists in the labor market. Results There was a reduction in the working hours of residents in training in the intensive care unit, and an increase in the outpatient activities of primary and secondary prevention. Also, the didactic content was reformulated and became organized by the corresponding division. Conclusion The update of the curriculum track of the InCor medical residency program was required in order to adapt it to the Brazilian labor market. The commission in charge of this update is aware that this is a dynamic process that may need changes over time.

Effect of psychotherapy on recurrence of events and quality of life in patients with vasovagal syncope.

Emotional distress is related to recurrence of syncope compromising patient's quality of life (QoL). The aim of this study was to determine if weekly sessions of psychotherapy reduce recurrence of events and improve QoL by SF-36 among patients with refractory vasovagal syncope. A randomised controlled pilot trial including 10 patients with recurrent vasovagal syncope and positive tilt table test was conducted. Known cardiac disease and ongoing psychotherapeutic interventions were the main exclusion criteria. All patients received standard of care treatment. Additionally, after randomisation, half of the patients underwent weekly sessions of psychotherapy for 12 months. Analysis of recurrence of events and QoL showed no significant change in the control group but, in the intervention group, there was a significant reduction in the rate of near-syncope episodes per month (5.7 ± 1.4 × 1.7 ± 1.0; P < 0.01), syncope in 1 year (4.6 ± 0.9 × 1.0 ± 0.7; P < 0.01) and a significant improvement in the overall assessment of QoL (44.1 ± 10.0 vs. 70.3 ± 10.3, P < 0.01). In conclusion, patients with refractory vasovagal syncope undergoing regular psychotherapeutic intervention had less recurrence of events and improved their quality of life in 1 year.Trial Registration: ClinicalTrials.gov number, NCT04252729.

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.

Arterial stiffness and atrial fibrillation: A review.

Arterial stiffness has been investigated as part of the physiopathology of arterial hypertension since the 1970s. Its role in increasing the "pulsatile load" imposed over the Left Ventricle (LV) has been intensely studied recently and has helped in understanding the mechanisms of Atrial Fibrillation (AF) in hypertensive patients. This paper aims to review the main evidence on this issue and establish possible mechanisms involved in the development of AF in patients with arterial stiffness. A PubMed search was performed, and selected articles were searched for references focusing on this topic. In the long term, lower blood pressure levels allow for arterial wall remodeling, leading to a lower stiffness index. To this day, however, there are no available treatments that directly promote the lowering of arterial wall stiffness. Most classes of anti-hypertensive drugs ‒ with stronger evidence for beta-blockers and diuretics ‒ could be effective in reducing arterial stiffness. There is strong evidence demonstrating an association between arterial stiffness and AF. New studies focusing on arterial stiffness and pre-fibrillatory stages would strengthen this causality relation.

Arterial stiffness and atrial fibrillation: A review

ABSTRACT Arterial stiffness has been investigated as part of the physiopathology of arterial hypertension since the 1970s. Its role in increasing the "pulsatile load" imposed over the Left Ventricle (LV) has been intensely studied recently and has helped in understanding the mechanisms of Atrial Fibrillation (AF) in hypertensive patients. This paper aims to review the main evidence on this issue and establish possible mechanisms involved in the development of AF in patients with arterial stiffness. A PubMed search was performed, and selected articles were searched for references focusing on this topic. In the long term, lower blood pressure levels allow for arterial wall remodeling, leading to a lower stiffness index. To this day, however, there are no available treatments that directly promote the lowering of arterial wall stiffness. Most classes of anti-hypertensive drugs ‒ with stronger evidence for beta-blockers and diuretics ‒ could be effective in reducing arterial stiffness. There is strong evidence demonstrating an association between arterial stiffness and AF. New studies focusing on arterial stiffness and pre-fibrillatory stages would strengthen this causality relation.

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.