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.

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.

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.

Evaluation of a pharmacogenetic-based warfarin dosing algorithm in patients with low time in therapeutic range - study protocol for a randomized controlled trial.

BACKGROUND: Time in therapeutic range (TTR) is a measurement of quality of warfarin therapy and lower TTR values (<50%) are associated with greater risk of thromboembolic and bleeding events. Recently, we developed a pharmacogenetic-based warfarin dosing algorithm specifically calibrated for a Brazilian patient sample. The aims of this study are: to evaluate the impact of a genetic-based algorithm, compared to traditional anticoagulation, in the time to achieve the therapeutic target and in TTR percentage; and to assess the cost-effectiveness of genotype-guided warfarin dosing in a specific cohort of patients with low TTR (<50%) from a tertiary cardiovascular hospital. METHODS/DESIGN: This study is a randomized controlled trial in patients (n = 300) with atrial fibrillation with TTR < 50%, based on the last three INR values. At the first consultation, patients will be randomized into two groups: TA group (traditional anticoagulation) and PA group (pharmacogenetic anticoagulation). For the first group, the physician will adjust the dose according to current INR value and, for the second group, a pharmacogenetic algorithm will be used. At the second, third, fourth and fifth consultations (with an interval of 7 days each) INR will be measured and, if necessary, the dose will be adjusted based on guidelines. Afterwards, patients who are INR stable will begin measuring their INR in 30 day intervals; if the patient's INR is not stable, the patient will return in 7 days for a new measurement of the INR. Outcomes measures will include the time to achieve the therapeutic target and the percentage of TTR at 4 and 12 weeks. In addition, as a secondary end-point, pharmacoeconomic analysis will be carried out. Ethical approval was granted by the Ethics Committee for Medical Research on Human Beings of the Clinical Hospital of the University of São Paulo Medical School. DISCUSSION: This randomized study will include patients with low TTR and it will evaluate whether a population-specific genetic algorithm might be more effective than traditional anticoagulation for a selected group of poorly anticoagulated patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02592980 . Registered on 29 October 2015.

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.

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.

[Update on ablation of ventricular tachyarrhythmias]. / Update Ablation ventrikulärer Tachyarrhythmien.

Catheter ablation of ventricular tachycardia (VT) is performed with increasing frequency in clinical practice. Whereas the reported success rates of idiopathic VT are high, catheter ablation of VT in patients with structural heart disease with its scar-related re-entry mechanism may remain a challenge especially if deep intramyocardial or epicardial portions exist. The integration of modern cardiac imaging, new functional mapping strategies and catheter technologies allow optimized identification and characterization of the critical arrhythmogenic substrate and hence a more targeted VT ablation. The extent to which these innovations will have the potential to improve VT ablation success rates will be determined by future studies.

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.

Bipolar radiofrequency ablation of septal ventricular tachycardia in a patient with dilated cardiomyopathy using two 8-mm tip catheters-case report.

Septal ventricular tachycardias exhibit high recurrence rates after radiofrequency ablation, which is mainly attributed to the deep intramyocardial circuits and the inability to create transmural lesions with the conventional unipolar ablation. Bipolar radiofrequency ablation is feasible and it has been reported as a valid technique in these cases, leading to deeper lesion formation, high non-inducibility rates, and acceptable recurrence rates during follow-up. Our goal is to report a successful case of bipolar ablation of a septal ventricular tachycardia using a simple bipolar ablation configuration with two 8-mm tip catheters.

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.

Transatrial management of inadvertent puncture of the posterior wall during transseptal access for atrial fibrillation ablation: technical report.

Transseptal puncture for atrial fibrillation ablation is a safe and common procedure. However, complications, such as cardiac tamponade, may be fatal if not recognized and treated. Our goal is to report a bailout strategy, by which management of an inadvertent puncture of the posterior wall of the left atrium was possible. It was followed by successful pulmonary vein isolation, without the need for subsequent subxiphoid puncture.

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.

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.

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

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 ß-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 ß-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 ß-blocker use to evaluate the expression of ß-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 ß-3 (37.41 vs 34.18, p=0.039) and GRK-5 (51.16 vs 47.66; p<0.001). ß-blocker use had no impact on ß-receptor expression. CONCLUSION: Increased ICANS innervation and remodeling receptor expression in regions prone to triggering AF may play a role in permanent AF.

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 ß-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 ß-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 ß e GRK-5, pelo uso de ß-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 ß-3 (37,41 vs 34,18, p =0,04) e GRK-5 (51,16 vs 47,66; p<0,01). O uso de ß-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.

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.

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.

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.

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.