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.

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.

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.

Prognosis of chronic Chagas heart disease and other pending clinical challenges

In this chapter, the main prognostic markers of Chagas heart disease are addressed, with an emphasis on the most recent findings and questions, establishing the basis for a broad discussion of recommendations and new approaches to managing Chagas cardiopathy. The main biological and genetic markers and the contribution of the electrocardiogram, echocardiogram and cardiac magnetic resonance are presented. We also discuss the most recent therapeutic proposals for heart failure, thromboembolism and arrhythmias, as well as current experience in heart transplantation in patients suffering from severe Chagas cardiomyopathy. The clinical and epidemiological challenges introduced by acute Chagas disease due to oral contamination are discussed. In addition, we highlight the importance of ageing and comorbidities in influencing the outcome of chronic Chagas heart disease. Finally, we discuss the importance of public policies, the vital role of funding agencies, universities, the scientific community and health professionals, and the application of new technologies in finding solutions for better management of Chagas heart disease.

Amiodarone-Induced Thyrotoxicosis - Literature Review & Clinical Update. / Tireotoxicose Induzida pela Amiodarona - Revisão de Literatura e Atualização Clínica.

Amiodarone is widely used in treating atrial and ventricular arrhythmias; however, due to its high iodine concentration, the chronic use of the drug can induce thyroid disorders. Amiodarone-induced thyrotoxicosis (AIT) can decompensate and exacerbate underlying cardiac abnormalities, leading to increased morbidity and mortality, especially in patients with left ventricular ejection fraction <30%. AIT cases are classified into two subtypes that guide therapeutic management. The risks and benefits of maintaining the amiodarone must be evaluated individually, and the therapeutic decision should be taken jointly by cardiologists and endocrinologists. Type 1 AIT treatment is similar to that of spontaneous hyperthyroidism, using antithyroid drugs (methimazole and propylthiouracil) at high doses. Type 1 AIT is more complicated since it has proportionally higher recurrences or even non-remission, and definitive treatment is recommended (total thyroidectomy or radioiodine). Type 2 AIT is generally self-limited, yet due to the high mortality associated with thyrotoxicosis in cardiac patients, the treatment should be implemented for faster achievement of euthyroidism. Furthermore, in well-defined cases of type 2 AIT, the treatment with corticosteroids is more effective than treatment with antithyroid drugs. In severe cases, regardless of subtype, immediate restoration of euthyroidism through total thyroidectomy should be considered before the patient progresses to excessive clinical deterioration, as delayed surgery indication is associated with increased mortality.

A amiodarona é amplamente utilizada no tratamento de arritmias atriais e ventriculares, porém devido sua alta concentração de iodo, o uso crônico da droga pode induzir distúrbios tireoidianos. A tireotoxicose induzida pela amiodarona (TIA) pode descompensar e exacerbar anormalidades cardíacas subjacentes, provocando aumento da morbidade e mortalidade, principalmente em pacientes com fração de ejeção do ventrículo esquerdo <30%. Os casos de TIA são classificados em dois subtipos que direcionam a conduta terapêutica. Os riscos e benefícios de manter a amiodarona devem ser avaliados de maneira individualizada, e a decisão de continuar ou suspender a droga deve ser tomada conjuntamente por cardiologistas e endocrinologistas. O tratamento de TIA tipo 1 é semelhante ao do hipertireoidismo espontâneo, sendo indicado o uso de drogas antitireoidianas (metimazol e propiltiouracil) em doses elevadas. A TIA tipo 1 mostra-se mais complicada, pois apresenta proporcionalmente maiores números de recorrências ou até mesmo a não remissão do quadro, sendo recomendado o tratamento definitivo (tireoidectomia total ou radioiodo). TIA tipo 2 é geralmente autolimitada, mas devido a elevada mortalidade associada a tireotoxicose em pacientes cardiopatas, o tratamento deve ser instituído para que o eutireoidismo seja atingido mais rapidamente. Em casos bem definidos de TIA tipo 2, o tratamento com corticosteroides é mais efetivo do que o tratamento com drogas antitireoidianas. Em casos graves, independentemente do subtipo, a restauração imediata do eutiroidismo por meio da tireoidectomia total deve ser considerada antes que o paciente evolua com piora clínica excessiva, pois a demora na indicação da cirurgia está associada ao aumento da mortalidade.

A Remodelação do Sistema Nervoso Autônomo Cardíaco pode Desempenhar um Papel na Fibrilação Atrial: Um Estudo do Sistema Nervoso Autônomo e Receptores Miocárdicos / Cardiac Autonomic Nervous System Remodeling May Play a Role in Atrial Fibrillation: A Study of the Autonomic Nervous System and Myocardial Receptors

Resumo Fundamento Alterações do substrato elétrico e anatômico do coração são fatores que originam e perpetuam a fibrilação atrial (FA), porém, os mecanismos envolvidos não foram totalmente elucidados ainda. Objetivo: Avaliar o papel do remodelamento do sistema nervoso cardíaco intrínseco (SNCI), incluindo fibras nervosas e receptores muscarínicos e β-adrenérgicos, na FA permanente humana. Métodos Foram avaliadas 4 amostras em átrios de 13 corações obtidos em necrópsias de pacientes com doença cardíaca e FA permanente, e em 13 controles com as mesmas doenças, porém, sem FA. Utilizando imunoperoxidase e histomorfometria, quantificamos a densidade das fibras do SNCI, bem como a porcentagem positiva de miocárdio para receptores β-adrenérgicos 1, 2 e 3, receptor quinase 5 acoplado à proteína G (GRK-5), e receptores muscarínicos 1 a 5. Os resultados foram comparados usando ANOVA e ANOVA hierarquizada e ajustados pelo volume do átrio esquerdo e, para avaliação da expressão de receptores β e GRK-5, pelo uso de β-bloqueadores. Adotamos como significativo α = 0,05. Resultados Houve aumento na densidade das fibras ( p <0,01), especialmente nas fibras simpáticas ( p =0,02). Quanto aos receptores muscarínicos, só houve diferença nos M1, que estavam aumentados (5,87±4,52 vs 2,85±2,40; p =0,03). Quanto aos componentes do sistema adrenérgicos analisados, houve expressão aumentada de β-3 (37,41 vs 34,18, p =0,04) e GRK-5 (51,16 vs 47,66; p<0,01). O uso de β-bloqueadores não teve impacto na expressão de receptores beta. Conclusão O aumento na inervação do SNCI e a alteração na expressão de receptores em regiões suscetíveis de desencadear FA podem ter um papel na fibrilação atrial permanente.

Abstract Background The primary factors that originate and perpetuate atrial fibrillation (AF) are electrical and anatomical substrate alterations. However, the central mechanisms governing AF perpetuation have not been elucidated yet, which is reflected on the modest results of the treatment in patients with long persistent AF. Objective To evaluate if human intrinsic cardiac autonomic nervous system (ICANS) remodeling, including nervous system fibers and muscarinic and β-adrenergic receptors, play a role in permanent AF. Methods Heart necropsy samples from thirteen patients with heart disease and permanent AF and thirteen controls without AF were used. By using immunoperoxidase and histomorphometry quantification, we identified the following: the density of all fibers of the ICANS, sympathetic and parasympathetic fibers; and the percentage of myocardium positive for β-adrenergic receptors 1, 2 and 3; G protein-coupled receptor kinase-5 (GRK-5); and muscarinic receptors M1 to M5. The results were compared using ANOVA and nested ANOVA and were adjusted according to the left atrium volume for all variables, and β-blocker use to evaluate the expression of β-receptors and GRK-5. Results There was an overall increase in the density of fibers of the ICANS (p=0.006), especially in atrial sympathetic nerve fibers (p=0.017). Only M1 muscarinic receptors were increased (5.87 vs 2.35, p=0.032). For adrenergic receptors, the results were positive for increased expression of β-3 (37.41 vs 34.18, p=0.039) and GRK-5 (51.16 vs 47.66; p<0.001). β-blocker use had no impact on β-receptor expression. Conclusion Increased ICANS innervation and remodeling receptor expression in regions prone to triggering AF may play a role in permanent AF.

Tireotoxicose induzida pela amiodarona - revisão de literatura e atualização clínica / Amiodarone-induced thyrotoxicosis - literature review & clinical update

Resumo A amiodarona é amplamente utilizada no tratamento de arritmias atriais e ventriculares, porém devido sua alta concentração de iodo, o uso crônico da droga pode induzir distúrbios tireoidianos. A tireotoxicose induzida pela amiodarona (TIA) pode descompensar e exacerbar anormalidades cardíacas subjacentes, provocando aumento da morbidade e mortalidade, principalmente em pacientes com fração de ejeção do ventrículo esquerdo <30%. Os casos de TIA são classificados em dois subtipos que direcionam a conduta terapêutica. Os riscos e benefícios de manter a amiodarona devem ser avaliados de maneira individualizada, e a decisão de continuar ou suspender a droga deve ser tomada conjuntamente por cardiologistas e endocrinologistas. O tratamento de TIA tipo 1 é semelhante ao do hipertireoidismo espontâneo, sendo indicado o uso de drogas antitireoidianas (metimazol e propiltiouracil) em doses elevadas. A TIA tipo 1 mostra-se mais complicada, pois apresenta proporcionalmente maiores números de recorrências ou até mesmo a não remissão do quadro, sendo recomendado o tratamento definitivo (tireoidectomia total ou radioiodo). TIA tipo 2 é geralmente autolimitada, mas devido a elevada mortalidade associada a tireotoxicose em pacientes cardiopatas, o tratamento deve ser instituído para que o eutireoidismo seja atingido mais rapidamente. Em casos bem definidos de TIA tipo 2, o tratamento com corticosteroides é mais efetivo do que o tratamento com drogas antitireoidianas. Em casos graves, independentemente do subtipo, a restauração imediata do eutiroidismo por meio da tireoidectomia total deve ser considerada antes que o paciente evolua com piora clínica excessiva, pois a demora na indicação da cirurgia está associada ao aumento da mortalidade.

Abstract Amiodarone is widely used in treating atrial and ventricular arrhythmias; however, due to its high iodine concentration, the chronic use of the drug can induce thyroid disorders. Amiodarone-induced thyrotoxicosis (AIT) can decompensate and exacerbate underlying cardiac abnormalities, leading to increased morbidity and mortality, especially in patients with left ventricular ejection fraction <30%. AIT cases are classified into two subtypes that guide therapeutic management. The risks and benefits of maintaining the amiodarone must be evaluated individually, and the therapeutic decision should be taken jointly by cardiologists and endocrinologists. Type 1 AIT treatment is similar to that of spontaneous hyperthyroidism, using antithyroid drugs (methimazole and propylthiouracil) at high doses. Type 1 AIT is more complicated since it has proportionally higher recurrences or even non-remission, and definitive treatment is recommended (total thyroidectomy or radioiodine). Type 2 AIT is generally self-limited, yet due to the high mortality associated with thyrotoxicosis in cardiac patients, the treatment should be implemented for faster achievement of euthyroidism. Furthermore, in well-defined cases of type 2 AIT, the treatment with corticosteroids is more effective than treatment with antithyroid drugs. In severe cases, regardless of subtype, immediate restoration of euthyroidism through total thyroidectomy should be considered before the patient progresses to excessive clinical deterioration, as delayed surgery indication is associated with increased mortality.

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.

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.

Effects of anthracycline, cyclophosphamide and taxane chemotherapy on QTc measurements in patients with breast cancer.

AIM: Acute and subacute cardiotoxicity are characterized by prolongation of the corrected QT interval (QTc) and other measures derived from the QTc interval, such as QTc dispersion (QTdc) and transmural dispersion of repolarization (DTpTe). Although anthracyclines prolong the QTc interval, it is unclear whether breast cancer patients who undergo the ACT chemotherapy regimen of anthracycline (doxorubicin: A), cyclophosphamide (C) and taxane (T) may present with QTc, QTdc and DTpTe prolongation. METHODS: Twenty-three consecutive patients with breast cancer were followed prospectively during ACT chemotherapy and were analyzed according to their QT measurements. QTc, QTdc and DTpTe measurements were determined by a 12-lead electrocardiogram (EKG) prior to chemotherapy (baseline), immediately after the first phase of anthracycline and cyclophosphamide (AC) treatment, and immediately after T treatment. Serum troponin and B-type natriuretic peptide (BNP) levels were also measured. RESULTS: Compared to baseline values, the QTc interval was significantly prolonged after the AC phase (439.7 ± 33.2 ms vs. 472.5 ± 36.3 ms, p = 0.001) and after T treatment (439.7 ± 33.2 ms vs. 467.9 ± 42.6 ms, p < 0.001). Troponin levels were elevated after the AC phase (23.0 pg/mL [min-max: 6.0-85.0] vs. 6.0 pg/mL [min-max: 6.0-22.0], p < 0.001) and after T treatment (25.0 pg/mL [min-max: 6.0-80.0] vs. 6.0 pg/mL [min-max: 6.0-22.0], p < 0.001) compared to baseline values. CONCLUSION: In this prospective study of patients with non-metastatic breast cancer who underwent ACT chemotherapy, significant QTc prolongation and an elevation in serum troponin levels were observed.

Percutaneous Catheter Ablation of Epicardial Accessory Pathways.

Radiofrequency (RF) catheter ablation is the treatment of choice in patients with accessory pathways (APs) and Wolff-Parkinson-White syndrome. Endocardial catheter ablation has limitations, including the inability to map and ablate intramural or subepicardial APs. Some of these difficulties can be overcome using an epicardial approach performed through the epicardial venous system or by percutaneous catheterisation of the pericardial space. When a suspected left inferior or infero-paraseptal AP is refractory to ablation or no early activation is found at the endocardium, a transvenous approach via the coronary sinus is warranted because such epicardial pathways can be in close proximity to the coronary venous system. Associated congenital abnormalities, such as right atrial appendage, right ventricle diverticulum, coronary sinus diverticulum and absence of coronary sinus ostium, may also hamper a successful outcome. Percutaneous epicardial subxiphoid approach should be considered when endocardial or transvenous mapping and ablation fails. Epicardial mapping may be successful. It can guide and enhance the effectiveness of endocardial ablation. The finding of no epicardial early activation leads to a more persistent new endocardial attempt. When both endocardial and epicardial ablation are unsuccessful, open-chest surgery is the only option to eliminate the AP.

Atrial-oesophageal fistula following percutaneous radiofrequency catheter ablation of atrial fibrillation: the risk still persists.

Aims: Atrial-oesophageal fistula is a serious complication related to ablation of atrial fibrillation. As its occurrence is rare, there is a great lack of information about their mechanisms, incidence, presentations, and treatment. The objective of this manuscript is to present a series of cases of atrial-oesophageal fistula in Brazil, focusing on incidence, clinical presentation, and follow-up. Methods and results: This is a retrospective multicentre registry of atrial-oesophageal fistula cases that occurred in eight Brazilian centres from 2003 to 2015. Ten cases (0.113%) of atrial-oesophageal fistula were reported in 8863 ablation procedures in the period. Most of the subjects were male (70%) with age 59.6 ± 9.3 years. Eight centres were reference units in atrial fibrillation ablation with an experience over than 200 procedures at the time of fistula occurrence. Oesophageal temperature monitoring was performed in eight cases using coated sensors in six. The first atrial-oesophageal fistula clinical manifestation was typically fever (in six patients), with a median onset time of 16.5 (12­43) days after ablation. There was a delay of 7.8 ± 3.3 days between the first manifestation and the diagnosis in five patients. The treatment was surgical in six cases, clinical in three and stenting in one. Seven patients died (70%) and two developed permanent neurological sequelae. Conclusion: Atrial-oesophageal fistula remains a serious complication following AF ablation despite the incorporation of protective measures and increased technical experience of the groups. The high morbidity and mortality despite the treatment indicates the need to develop adequate preventive strategies.

Compound Heterozygous SCN5A Mutations in a Toddler - Are they Associated with a More Severe Phenotype? / Heterozigose Composta no Gene SCN5A em Criança - Há Associação com Gravidade da Doença?

Abstract Compound heterozygosity has been described in inherited arrhythmias, and usually associated with a more severe phenotype. Reports of this occurrence in Brugada syndrome patients are still rare. We report a study of genotype-phenotype correlation after the identification of new variants by genetic testing. We describe the case of an affected child with a combination of two different likely pathogenic SCN5A variants, presenting sinus node dysfunction, flutter and atrial fibrillation, prolonged HV interval, spontaneous type 1 Brugada pattern in the prepubescent age and familiar history of sudden death.

Resumo A heterozigose composta é descrita em arritmias hereditárias, geralmente associada a um fenótipo mais grave. Relatos dessa ocorrência em pacientes com síndrome de Brugada ainda são raros. Neste estudo, descrevemos o caso de uma criança com a combinação de duas novas variantes distintas no gene SCN5A, apresentando disfunção do nó sinusal, flutter e fibrilação atrial, intervalo HV prolongado, padrão tipo 1 espontâneo de Brugada na idade pré-puberal e história familiar de morte súbita.