Validation of qrs-polarity algorithm with special emphasis in parahisian pathways / Validación del algoritmo de la polaridad del qrs con especial énfasis en vías parahisianas

Abstract Background: In 1996 Iturralde et al. published an algorithm based on the QRS polarity to determine the location of the accessory pathways (AP), this algorithm was developed before the massive practice of invasive electrophysiology. Purpose: To validate the QRS-Polarity algorithm in a modern cohort of subjects submitted to radiofrequency catheter ablation (RFCA). Our objective was to determinate its global accuracy and its accuracy for parahisian AP. Methods: We conducted a retrospective analysis of patients with Wolff-Parkinson-White (WPW) syndrome who underwent an electrophysiological study (EPS) and RFCA. We employed the QRS-Polarity algorithm to predict the AP anatomical location and we compared this result with the real anatomic location determined in the EPS. To determine accuracy, the Cohen's kappa coefficient (k) and the Pearson correlation coefficient were used. Results: A total of 364 patients were included (mean age 30 years, 57% male). The global k score was 0.78 and the Pearson's coefficient was 0.90. The accuracy for each zone was also evaluated, the best correlation was for the left lateral AP (k of 0.97). There were 26 patients with a parahisian AP, who showed a great variability in the ECG features. Employing the QRS-Polarity algorithm, 34.6% patients had a correct anatomical location, 42.3% had an adjacent location and only 23% an incorrect location. Conclusion: The QRS-Polarity algorithm has a good global accuracy; its precision is high, especially for left lateral AP. This algorithm is also useful for the parahisian AP.

Resumen Antecedentes: En 1996 Iturralde y colaboradores publicaron un algoritmo basado en la polaridad del QRS para determinar la ubicación de las vías accesorias (VA), este algoritmo fue desarrollado antes de la práctica masiva de la electrofisiología invasiva. Objetivo: Validar el algoritmo de la polaridad del QRS en una cohorte moderna de sujetos sometidos a ablación con catéter por radiofrecuencia (ACRF). Nuestro objetivo fue determinar su precisión global y su precisión para las VA parahisianas. Métodos: Realizamos un análisis retrospectivo de pacientes con síndrome de Wolff-Parkinson-White (WPW) a los que se les realizó estudio electrofisiológico (EEF) y ACRF. Empleamos el algoritmo de la polaridad del QRS para predecir la ubicación anatómica de la VA y comparamos este resultado con la ubicación anatómica real determinada en el EEF. Para determinar la precisión se utilizaron el coeficiente kappa de Cohen (k) y el coeficiente de correlación de Pearson. Resultados: Se incluyeron un total de 364 pacientes (edad media 30 años, 57 % varones). La puntuación k global fue de 0,78 y el coeficiente de Pearson de 0,90. También se evaluó la precisión para cada zona, la mejor correlación fue para las VA laterales izquierdas (k de 0.97). Hubo 26 pacientes con VA parahisianas, que mostraron una gran variabilidad en las características del ECG. Empleando el algoritmo de la polaridad del QRS, el 34,6 % de los pacientes tenía una ubicación anatómica correcta, el 42,3 % tenía una ubicación adyacente y solo el 23 % una ubicación incorrecta. Conclusión: El algoritmo de la polaridad del QRS tiene una buena precisión global; su precisión es alta, especialmente para VA lateral izquierdo. Este algoritmo también es útil para la VA parahisiana.

Bioinformatics Insights on the Physicochemical Properties of SCN5A Mutant Proteins Associated with the Brugada Syndrome.

BACKGROUND: The Brugada syndrome (BrS) is a heart rhythm condition that is commonly associated with a strong predisposition for sudden cardiac death. Malignant ventricular arrhythmias could occur secondary to the dysfunction of the cardiac sodium voltage-gated Na(v)1.5 channel (SCN5A). OBJECTIVE: This study aimed to perform a multiparametric computational analysis of the physicochemical properties of SCN5A mutants associated with BrS using a set of bioinformatics tools. METHODS: In-house algorithms were calibrated to calculate, in a double-blind test, the Polarity Index Method (PIM) profile and protein intrinsic disorder predisposition (PIDP) profile of each sequence, and computer programs specialized in the genomic analysis were used. RESULTS: Specific regularities in the charge/polarity and PIDP profile of the SCN5A mutant proteins enabled the re-creation of the taxonomy, allowing us to propose a bioinformatics method that takes advantage of the PIM profile to identify this group of proteins from their sequence. CONCLUSION: Bioinformatics programs could reproduce characteristic PIM and PIDP profiles of the BrS-related SCN5A mutant proteins. This information can contribute to a better understanding of these altered proteins.

Individual Factors Associated With COVID-19 Infection: A Machine Learning Study.

The fast, exponential increase of COVID-19 infections and their catastrophic effects on patients' health have required the development of tools that support health systems in the quick and efficient diagnosis and prognosis of this disease. In this context, the present study aims to identify the potential factors associated with COVID-19 infections, applying machine learning techniques, particularly random forest, chi-squared, xgboost, and rpart for feature selection; ROSE and SMOTE were used as resampling methods due to the existence of class imbalance. Similarly, machine and deep learning algorithms such as support vector machines, C4.5, random forest, rpart, and deep neural networks were explored during the train/test phase to select the best prediction model. The dataset used in this study contains clinical data, anthropometric measurements, and other health parameters related to smoking habits, alcohol consumption, quality of sleep, physical activity, and health status during confinement due to the pandemic associated with COVID-19. The results showed that the XGBoost model got the best features associated with COVID-19 infection, and random forest approximated the best predictive model with a balanced accuracy of 90.41% using SMOTE as a resampling technique. The model with the best performance provides a tool to help prevent contracting SARS-CoV-2 since the variables with the highest risk factor are detected, and some of them are, to a certain extent controllable.

Andersen-Tawil Syndrome with High Risk of Sudden Cardiac Death in Four Mexican Patients. Cardiac and Extra-Cardiac Phenotypes

ABSTRACT Background: Andersen-Tawil syndrome (ATS) is a cardiac channelopathy that is inherited in an autosomal dominant way, and it is characterized by a triad of periodic paralysis, ventricular arrhythmias, and includes some dysmorphic features with incomplete penetrance and variable expression that result in a challenging diagnosis. Objective: The objective of the study was to describe the cardiac and extra-cardiac phenotype in a cohort of patients with ATS at risk of sudden cardiac death (SCD) to improve its early clinical identification. Methods: In an observational, transversal study, with a deviant case sampling, four female patients with ATS at high risk of SCD were included in the study. They carried the heterozygous pathogenic variants c.407C>T [p.Ser136Phe], c.652C>T [p.Arg218Trp] (n=2), and c.431G>C [p.Gly144Ala] in the KCNJ2 gene. Patients were evaluated by a cardiologist, a clinical geneticist, and a physiatrist. Results: One patient had the classical facial phenotype and the other three had subtle manifestations. The group of patients presented a diverse set of clinical data such as: triangular face, broad forehead, broadening of medial eyebrows, auricular pits, low-set ears, eyelid ptosis, thin lips, mandibular hypoplasia, and diverse types of dental alterations, single transverse palmar crease, camptodactyly, and syndactyly. Long-exercise test showed a decrement in the percentage amplitude up to 44%, classifying patients in IV or V types according to Fournier’s scale. Conclusions: Extra-cardiac manifestations were a common finding in this series of ATS type1 at high risk of SCD. Its recognition could help the clinician in the early identification of patients with ATS, especially for the cardiologist since they are commonly referred only for evaluation of ventricular arrhythmias.

Ambulatory Patients with Cardiometabolic Disease and Without Evidence of COVID-19 During the Pandemic. The CorCOVID LATAM Study.

Background: SARS-CoV-2 pandemic has modified the cardiovascular care of ambulatory patients. The aim of this survey was to study changes in lifestyle habits, treatment adherence, and mental health status in patients with cardiometabolic disease, but no clinical evidence of COVID-19. Methods: A cross-sectional survey was conducted in ambulatory patients with cardiometabolic disease using paper/digital surveys. Variables investigated included socioeconomic status, physical activity, diet, tobacco use, alcohol intake, treatment discontinuation, and psychological symptoms. Results: A total of 4,216 patients (50.9% males, mean age 60.3 ± 15.3 years old) from 13 Spanish-speaking Latin American countries were enrolled. Among the study population, 46.4% of patients did not have contact with a healthcare provider, 31.5% reported access barriers to treatments and 17% discontinued some medication. Multivariate analysis showed that non-adherence to treatment was more prevalent in the secondary prevention group: peripheral vascular disease (OR 1.55, CI 1.08-2.24; p = 0.018), heart failure (OR 1.36, CI 1.05-1.75; p = 0.017), and coronary artery disease (OR 1.29 CI 1.04-1.60; p = 0.018). No physical activity was reported by 38% of patients. Only 15% of patients met minimum recommendations of physical activity (more than 150 minutes/week) and vegetable and fruit intake. Low/very low income (45.5%) was associated with a lower level of physical activity (p < 0.0001), less fruit and vegetables intake (p < 0.0001), more tobacco use (p < 0.001) and perception of depression (p < 0.001). Low educational level was also associated with the perception of depression (OR 1.46, CI 1.26-1.70; p < 0.01). Conclusions: Patients with cardiometabolic disease but without clinical evidence of COVID-19 showed significant medication non-adherence, especially in secondary prevention patients. Deterioration in lifestyle habits and appearance of depressive symptoms during the pandemic were frequent and related to socioeconomic status.

Anticipation of ventricular tachyarrhythmias by a novel mathematical method: Further insights towards an early warning system in implantable cardioverter defibrillators.

Implantable cardioverter defibrillators (ICD) are the most effective therapy to terminate malignant ventricular arrhythmias (VA) and therefore to prevent sudden cardiac death. Until today, there is no way to predict the onset of such VA. Our aim was to develop a mathematical model that could predict VA in a timely fashion. We analyzed the time series of R-R intervals from 3 groups. Two groups from the Spontaneous Ventricular Tachyarrhythmia Database (v 1.0) were analyzed from a set of 81 pairs of R-R interval time series records from patients, each pair containing one record before the VT episode (Dataset 1A) and one control record which was obtained during the follow up visit (Dataset 1B). A third data set was composed of the R-R interval time series of 54 subjects without a significant arrhythmia heart disease (Dataset 2). We developed a new method to transform a time series into a network for its analysis, the ε-regular graphs. This novel approach transforms a time series into a network which is sensitive to the quantitative properties of the time series, it has a single parameter (ε) to be adjusted, and it can trace long-range correlations. This procedure allows to use graph theory to extract the dynamics of any time series. The average of the difference between the VT and the control record graph degree of each patient, at each time window, reached a global minimum value of -2.12 followed by a drastic increase of the average graph until reaching a local maximum of 5.59. The global minimum and the following local maxima occur at the windows 276 and 393, respectively. This change in the connectivity of the graphs distinguishes two distinct dynamics occurring during the VA, while the states in between the 276 and 393, determine a transitional state. We propose this change in the dynamic of the R-R intervals as a measurable and detectable "early warning" of the VT event, occurring an average of 514.625 seconds (8:30 minutes) before the onset of the VT episode. It is feasible to detect retrospectively early warnings of the VA episode using their corresponding ε-regular graphs, with an average of 8:30 minutes before the ICD terminates the VA event.

Atrialized right ventricular chamber as a source of ventricular tachycardia in Ebstein's anomaly. Analysis of two successful catheter ablation cases.

Ventricular tachycardia in Ebstein's anomaly patients is rare and increases the risk of sudden death up to 6 times. We present two cases of Ebstein's anomaly, the first of them with a history of Glenn surgery and biological prosthesis at tricuspid position and the second case without surgical repair. Both admitted to the emergency room due to ventricular tachycardia poorly tolerated. Detailed substrate characterization and pace mapping showed fragmented signals in the area of atrialized right ventricle and correlated were pace mapping reproduced morphology identical to the clinical VT, ablation at this sites were successful without recurrence during follow-up.

Impact of the Pandemic on NonInfected Cardiometabolic Patients: A Survey in Countries of Latin America-Rationale and Design of the CorCOVID LATAM Study.

BACKGROUND: The first case of coronavirus 2019 (COVID-19) in Latin America was detected on February 26th, 2020, in Brazil. Later, in June, the World Health Organization announced that the focus of the outbreak had shifted to Latin America, where countries already had poor control of indicators of noncommunicable diseases (NCDs). Concerns about coronavirus infection led to a reduced number of visits and hospitalizations in patients with NCDs, such as cardiovascular disease, diabetes, and cancer. There is a need to determine the impact of the COVID-19 pandemic on patients who have cardiometabolic diseases but do not have clinical evidence of COVID-19 infection. METHODS: The CorCOVID LATAM is a cross-sectional survey of ambulatory cardiometabolic patients with no history or evidence of COVID-19 infection. The study will be conducted by the Interamerican Society of Cardiology. An online survey composed of 38 questions using Google Forms will be distributed to patients of 13 Latin American Spanish-speaking countries from June 15th to July 15th, 2020. Data will be analyzed by country and regions. Seven clusters of questions will be analyzed: demographics, socioeconomic and educational level, cardiometabolic profile, lifestyle and habits, body-weight perception, medical follow-up and treatments, and psychological symptoms. RESULTS: Final results will be available upon completion of the study. CONCLUSIONS: The present study will provide answers regarding the impact of the COVID-19 pandemic on noninfected cardiometabolic patients. Data on this topic are scarce, as it is an unprecedented threat, without short-term solutions.

CONTEXTE: Le premier cas de maladie à coronavirus 2019 (COVID-19) en Amérique latine a été détecté le 26 février 2020 au Brésil. En juin, l'Organisation mondiale de la Santé a annoncé que le foyer de l'épidémie s'était déplacé en Amérique latine, où le suivi des indicateurs relatifs aux maladies non transmissibles est déjà déficient. Les préoccupations relatives à l'infection par le coronavirus ont entraîné une diminution du nombre de consultations et d'hospitalisations des patients atteints d'une maladie non transmissible, comme une ma-ladie cardiovasculaire, le diabète ou un cancer. Il est donc nécessaire d'évaluer l'incidence de la pandémie de COVID-19 chez les patients atteints d'une maladie cardiométabolique ne présentant aucun signe clinique d'une infection au virus de la COVID-19. MÉTHODOLOGIE: L'étude CorCOVID LATAM est une enquête transversale menée auprès des patients ambulatoires atteints d'une maladie cardiométabolique n'ayant pas d'antécédents d'infection au virus de la COVID-19 et ne présentant aucun signe d'une telle infection. L'étude est réalisée par la Société interaméricaine de cardiologie. Du 15 juin au 15 juillet 2020, on a demandé aux patients de 13 pays hispanophones d'Amérique latine de répondre à un questionnaire en ligne de 38 questions dans Google Forms. Les données seront analysées par pays et par région. Les réponses aux questions seront examinées selon sept grands thèmes : caractéristiques démographiques, caractéristiques socioéconomiques et niveau de scolarité, profil cardiométabolique, mode de vie et habitudes, perception quant au poids corporel, suivi et traitements médicaux et symptômes psychologiques. RÉSULTATS: Les résultats seront publiés à la fin de l'étude. CONCLUSIONS: L'étude fournira des renseignements sur l'incidence de la pandémie de COVID-19 chez les patients atteints d'une maladie cardiométabolique non infectés. Les données sur cette question sont rares, puisqu'il s'agit d'une menace sans précédent, à laquelle il n'existe de surcroît pas de solution à court terme.

Hidroxicloroquina: Mensajes desde la cardiología en tiempos de pandemia por Coronavirus / Hydroxychloroquine. Cardiology's viewpoint in times of coronavirus pandemic

Ante la pandemia de COVID-19 (del inglés coronavirus disease 2019), uno de los fármacos propuesto para su tratamiento es la hidroxicloroquina. Se revisan aquí aspectos cardiológicos del uso de cloroquina e hidroxicloroquina. Se realizó una revisión no sistemática en la literatura médica orientada a la búsqueda de información acerca de su seguridad y eficacia como antimaláricos y antivirales, así como en el tratamiento prolongado de enfermedades reumatológicas. Se halló un efecto antiinflamatorio con reducción de eventos cardiovasculares a largo plazo, una cardiopatía muy infrecuente por un efecto lisosomal del fármaco, y a nivel hemodinámico hipotensión, taquicardia, y prolongación del intervalo QT, exacerbado si se combina con azitromicina. Sin embargo, la tasa de eventos adversos cardíacos de la hidroxicloroquina y la cloroquina fue baja.

Due to the coronavirus disease 2019 (COVID-19) pandemic, a wide number of compounds are under scrutiny regarding their antiviral activity, one of them being hydroxychloroquine. Cardiac aspects of the use of chloroquine and hydroxychloroquine are reviewed in this manuscript. A non-systematic review of the medical literature was performed. Information about their safety and efficacy as antimalarials, antivirals, as well as in the long-term treatment of rheumatic diseases was collected. We found an anti-inflammatory effect with reduction of long-term cardiovascular events, a very infrequent heart disease due to a lysosomal effect of the drug, and at the hemodynamic level hypotension, tachycardia, and QT interval prolongation, exacerbated when combined with azithromycin. However, the rate of adverse cardiac events of hydroxychloroquine (and chloroquine) was low.

Cardioinhibitory syncope: from pathophysiology to treatment-should we think on cardioneuroablation?

Vasovagal syncope (VVS) is the most common type of syncope; the lone cardioinhibitory syncope represents only a small group of patients; however, the "cardioinhibitory component" is highly prevalent in reflex syncope and can be severe enough to produce asystole, lasting for a few seconds followed by a recovery to sinus beats. The environment in which syncope occurs can compromise life, and in-depth knowledge of the disease can prevent deaths and guide the appropriate management. The therapeutic cornerstone is general measures (increase water and salt) followed by pharmacologic therapy; for cardioinhibitory syncope, both treatments fail most of the time, and the next therapeutic option is pacemaker implantation. However, although the pacemaker causes a reduction in syncope, recurrence is high, and a one-time, effective, and safe intervention would be ideal. Cardioneuroablation (CNA) therapy has been proposed as a pacemaker alternative with these characteristics. CNA has shown a high reduction or even complete syncope elimination during 3 years of follow-up in some studies. Patients also reported prolonged prodromal periods, which allowed them enough time to abort the syncope. Invasive therapies like CNA require further extensive cohort studies, randomized clinical trials, and more substantial follow-up to evaluate adverse side effects. This review highlights syncope pathophysiology, dividing it into a central theory and a peripheral theory, the diagnosis explaining the head-up tilt test protocols, and treatments like CAN, representing it with figures for a simplified understanding.

Joint Mexican position document on the treatment of atrial fibrillation / Posicionamiento conjunto acerca del tratamiento para fibrilación auricular

Abstract Atrial fibrillation (AF) is a frequent arrhythmia; its prevalence is near 2% in the general population; in Mexico, more than one-half million people are affected. AF needs to be considered as a public health problem. Because AF is an independent risk factor associated with mortality, due to embolic events, heart failure, or sudden death; early diagnosis is of utmost importance. In unstable patients with a recent onset of AF, electrical cardioversion should be practiced. In stable patients, once thromboembolic measures have been taken, it is necessary to assess whether it is reasonable to administer an antiarrhythmic drug to restore sinus rhythm or performed electrical cardioversion. For recidivating cases of paroxysmal and persistent presentation, the most effective strategy is performed pulmonary vein isolation with either radiofrequency or cryoballoon energy. Permanent AF is that in which recovery of sinus rhythm is not possible, the distinguishing feature of this phase is the uncontrollable variability of the ventricular frequency and could be treated pharmacologically with atrioventricular (AV) nodal blockers or with a VVIR pacemaker plus AV nodal ablation. The presence of AF has long been associated with the development of cerebral and systemic (pulmonary, limb, coronary, renal, and visceral) embolism. The prevention of embolisms in “valvular” AF should perform with Vitamin K antagonists (VKA). For patients with AF not associated with mitral stenosis or a mechanical valve prosthesis, a choice can be made between anticoagulant drugs, VKA, or direct oral anticoagulants. Antiplatelet agents have the weakest effect in preventing embolism.

Resumen La fibrilación auricular (FA) es una arritmia frecuente; su prevalencia es cercana al 2% en la población general, en México se ven afectados más de medio millón de personas por eso debe considerarse como un problema de salud pública. Debido a que la FA es un factor de riesgo independiente asociado a mortalidad, por eventos embólicos, insuficiencia cardíaca o muerte súbita, la identificación y diagnóstico temprano es de suma importancia. En el inicio reciente de FA en pacientes inestables, se debe practicar la cardioversión eléctrica. En pacientes estables, una vez que se han tomado medidas tromboembólicas, es necesario evaluar si es razonable administrar un medicamento antiarrítmico para restaurar el ritmo sinusal o realizar una cardioversión eléctrica. Para los casos que recidivan, ya sea paroxística o persistente, la estrategia más efectiva es realizar el aislamiento de la venas pulmonares con radiofrecuencia o crioablación con balón. La FA permanente es aquella en la que no es posible la recuperación del ritmo sinusal, la característica distintiva de esta fase de la FA es la variabilidad incontrolable de la frecuencia ventricular. Puede tratarse farmacológicamente con bloqueadores nodales AV o con un marcapasos VVIR mas ablación del nodo AV. La presencia de FA se ha asociado durante mucho tiempo con el desarrollo de embolia cerebral y sistémica (pulmonar, de extremidades, coronaria, renal y visceral). La prevención de embolias en la FA “valvular” debe realizarse con antagonistas de la vitamina K (AVK). Para los pacientes con FA no asociados con estenosis mitral o una prótesis valvular mecánica, se puede elegir entre medicamentos anticoagulantes, AVK o anticoagulantes orales directos (DOAC). Los agentes antiplaquetarios tienen el efecto más débil para prevenir la embolia.

Joint Mexican position document on the treatment of atrial fibrillation.

Atrial fibrillation (AF) is a frequent arrhythmia; its prevalence is near 2% in the general population; in Mexico, more than one-half million people are affected. AF needs to be considered as a public health problem. Because AF is an independent risk factor associated with mortality, due to embolic events, heart failure, or sudden death; early diagnosis is of utmost importance. In unstable patients with a recent onset of AF, electrical cardioversion should be practiced. In stable patients, once thromboembolic measures have been taken, it is necessary to assess whether it is reasonable to administer an antiarrhythmic drug to restore sinus rhythm or performed electrical cardioversion. For recidivating cases of paroxysmal and persistent presentation, the most effective strategy is performed pulmonary vein isolation with either radiofrequency or cryoballoon energy. Permanent AF is that in which recovery of sinus rhythm is not possible, the distinguishing feature of this phase is the uncontrollable variability of the ventricular frequency and could be treated pharmacologically with atrioventricular (AV) nodal blockers or with a VVIR pacemaker plus AV nodal ablation. The presence of AF has long been associated with the development of cerebral and systemic (pulmonary, limb, coronary, renal, and visceral) embolism. The prevention of embolisms in "valvular" AF should perform with Vitamin K antagonists (VKA). For patients with AF not associated with mitral stenosis or a mechanical valve prosthesis, a choice can be made between anticoagulant drugs, VKA, or direct oral anticoagulants. Antiplatelet agents have the weakest effect in preventing embolism.

La fibrilación auricular (FA) es una arritmia frecuente; su prevalencia es cercana al 2% en la población general, en México se ven afectados más de medio millón de personas por eso debe considerarse como un problema de salud pública. Debido a que la FA es un factor de riesgo independiente asociado a mortalidad, por eventos embólicos, insuficiencia cardíaca o muerte súbita, la identificación y diagnóstico temprano es de suma importancia. En el inicio reciente de FA en pacientes inestables, se debe practicar la cardioversión eléctrica. En pacientes estables, una vez que se han tomado medidas tromboembólicas, es necesario evaluar si es razonable administrar un medicamento antiarrítmico para restaurar el ritmo sinusal o realizar una cardioversión eléctrica. Para los casos que recidivan, ya sea paroxística o persistente, la estrategia más efectiva es realizar el aislamiento de la venas pulmonares con radiofrecuencia o crioablación con balón. La FA permanente es aquella en la que no es posible la recuperación del ritmo sinusal, la característica distintiva de esta fase de la FA es la variabilidad incontrolable de la frecuencia ventricular. Puede tratarse farmacológicamente con bloqueadores nodales AV o con un marcapasos VVIR mas ablación del nodo AV. La presencia de FA se ha asociado durante mucho tiempo con el desarrollo de embolia cerebral y sistémica (pulmonar, de extremidades, coronaria, renal y visceral). La prevención de embolias en la FA "valvular" debe realizarse con antagonistas de la vitamina K (AVK). Para los pacientes con FA no asociados con estenosis mitral o una prótesis valvular mecánica, se puede elegir entre medicamentos anticoagulantes, AVK o anticoagulantes orales directos (DOAC). Los agentes antiplaquetarios tienen el efecto más débil para prevenir la embolia.

Basic and clinical insights in catecholaminergic (familial) polymorphic ventricular tachycardia

Abstract Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal disease, whose characteristic ventricular tachycardias are adrenergic-dependent. Although rare, CPVT should be considered in the differential diagnosis of young individuals with exercise-induced syncope. Mutations in five different genes (RYR2, CASQ2, CALM1, TRDN, and TECRL) are associated with the CPVT phenotype, although RYR2 missense mutations are implicated in up to 60 % of all CPVT cases. Genetic testing has an essential role in the diagnosis, management, pre-symptomatic diagnosis, counseling, and treatment of the proband; furthermore, genetic information can be useful for offspring and relatives. By expert consensus, CPVT gene testing is a Class I recommendation for patients with suspected CPVT. Beta-adrenergic and calcium-channel blockers are the cornerstones of treatment due to the catecholaminergic dependence of the arrhythmias. Unresponsive patients are treated with an implantable cardioverter-defibrillator to reduce the risk of sudden cardiac death. In the present article, a brief review of the genetic and molecular mechanisms of this intriguing disease is provided.

POLYMORPHISMS IN ß-ADRENERGIC RECEPTORS ARE ASSOCIATED WITH INCREASED RISK TO HAVE A POSITIVE HEAD-UP TILT TABLE TEST IN PATIENTS WITH VASOVAGAL SYNCOPE.

BACKGROUND: Vasovagal syncope (VVS) is a frequent clinical condition in which a genetic background seems to be implicated. Considering that the adrenergic receptors (ARs) may play a role in VVS, the present study has as principal aim to determine if the α- and ß-AR (ADRA and ADRB) gene polymorphisms are associated with an increased risk to have a positive head-up tilt table (HUTT) test in patients with VVS. Methods: Nine polymorphisms in the ADRA1A (rs1048101, rs1383914, rs574584, and rs573542), ADRB1 (rs1801252 and rs1801253), ADRB2 (rs1042713 and rs1042714), and ADRB3 (rs4994) genes were analyzed using the 5' exonuclease TaqMan genotyping assay in a group of 134 patients with VVS. RESULTS: Under different models, the rs1801252 (OR = 8.63, 95% CI: 0.95-78.72, Precessive = 0.02), rs1042713 (OR = 1.94, 95% CI: 1.02-3.66, Padditive = 0.04), and rs4994 (OR = 2.46, 95% CI: 1.01-6.01, Pdominant = 0.042 and OR = 2.62, 95% CI: 1.04-6.63, Pover-dominant = 0.03) polymorphisms were associated with increased risk for a positive HUTT. All models were adjusted for statistically significant covariates. CONCLUSION: These results suggest that some polymorphisms of the ß-AR genes could contribute to a positive tilt test in patients with VVS.

Polymorphisms in ß-adrenergic receptors are associated with increased risk to have a positive head-up tilt table test in patients with vasovagal syncope

Abstract Background Vasovagal syncope (VVS) is a frequent clinical condition in which a genetic background seems to be implicated. Considering that the adrenergic receptors (ARs) may play a role in VVS, the present study has as principal aim to determine if the α- and β-AR (ADRA and ADRB) gene polymorphisms are associated with an increased risk to have a positive head-up tilt table (HUTT) test in patients with VVS. Methods: Nine polymorphisms in the ADRA1A (rs1048101, rs1383914, rs574584, and rs573542), ADRB1 (rs1801252 and rs1801253), ADRB2 (rs1042713 and rs1042714), and ADRB3 (rs4994) genes were analyzed using the 5’ exonuclease TaqMan genotyping assay in a group of 134 patients with VVS. Results Under different models, the rs1801252 (OR = 8.63, 95% CI: 0.95-78.72, Precessive = 0.02), rs1042713 (OR = 1.94, 95% CI: 1.02-3.66, Padditive = 0.04), and rs4994 (OR = 2.46, 95% CI: 1.01-6.01, Pdominant = 0.042 and OR = 2.62, 95% CI: 1.04-6.63, Pover-dominant = 0.03) polymorphisms were associated with increased risk for a positive HUTT. All models were adjusted for statistically significant covariates. Conclusion These results suggest that some polymorphisms of the β-AR genes could contribute to a positive tilt test in patients with VVS.

Gender differences and management of stroke risk of nonvalvular atrial fibrillation in an upper middle-income country: Insights from the CARMEN-AF registry.

BACKGROUND: Atrial Fibrillation (AF) is associated with an increased risk of stroke and systemic embolism. Several studies have suggested that female AF patients could have a greater risk for stroke. There is scarce information about clinical characteristics and use of antithrombotic therapies in Latin American patients with nonvalvular AF. OBJECTIVE: To describe the gender differences in clinical characteristics, thromboembolic risk, and antithrombotic therapy of patients with nonvalvular AF recruited in Mexico, an upper middle-income country, into the prospective national CARMEN-AF Registry. METHODS: A total of 1423 consecutive patients, with at least one thromboembolic risk factor were enrolled in CARMEN-AF Registry during a three-year period (2014-2017). They were categorized according to Gender. RESULTS: Overall, 48.6% were women, mean age 70 ±â€¯12 years. Diabetes, smoking, alcoholism, non-ischemic cardiomyopathy, coronary artery disease, and obstructive sleep apnea were higher in men. Most women were found with paroxysmal AF (40.6%), and most men with permanent AF (44.0%). No gender differences were found in the use of vitamin K antagonists (VKA) (30.5% in women vs. 28.0% in men). No gender differences were found in the use of direct oral anticoagulants (DOAC) (33.8% women vs 35.4% men). CONCLUSIONS: CARMEN-AF Registry demonstrates that in Mexico, regardless of gender, a large proportion of patients remain undertreated. No gender differences were found in the use of VKA or DOAC.