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Background: Osimertinib is a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor that has become the first-line treatment for non-small cell lung cancer harboring EGFR mutations, with the potential risk of QT prolongation and heart failure. However, few cases have reported malignant ventricular arrhythmias. Here, we report a case of recurrent ventricular fibrillation (VF) and Torsade de Pointes (TdP) secondary to QT prolongation and heart failure induced by osimertinib. Case summary: A 70-year-old woman presented with chest tightness and dyspnea for 1 week and ventricular fibrillation upon admission, with a medical history of lung adenocarcinoma harboring an EGFR exon 21 p.L858R mutation. She was under osimertinib for 3 months. Electrocardiography after defibrillation suggested QTc prolongation (655â ms) and T wave alternans. Ultrasound cardiography displayed left ventricular ejection fraction (LVEF) of 29% and severe mitral regurgitation. Laboratory tests indicated elevated N-terminal pro-B-type natriuretic peptide and hypokalemia. Genetic testing suggested no pathogenic mutations. We considered acquired long QT syndrome and heart failure with reduced ejection fraction induced by osimertinib as the chief causes of ventricular arrhythmia and hypokalemia as an important trigger. Despite intubation, sedation, and the administration intravenous magnesium and potassium and lidocaine, the patient presented with recurrent TdP, which was managed by a low dose of isoproterenol (ISO, 0.17â ug/min). An implantable cardioverter defibrillator was declined. The patient is surviving without any relapse, with QTc of 490â ms and LVEF of 42% after a 6-month follow up. Conclusion: Regular monitoring is required during osimertinib administration, considering the risk of life-threatening cardiac events, such as malignant arrhythmias and heart failure. ISO, with an individual dose and target heart rate, may be beneficial for terminating TdP during poor response to other therapies.
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Population studies report elevated incidence of cardiovascular events in patients with chronic epilepsy. Multiple pathophysiologic processes have been implicated, including accelerated atherosclerosis, myocardial infarction, altered autonomic tone, heart failure, atrial and ventricular arrhythmias, and hyperlipidemia. These deleterious influences on the cardiovascular system have been attributed to seizure-induced surges in catecholamines and hypoxemic damage to the heart and coronary vasculature. Certain antiseizure medications can accelerate heart disease through enzyme-inducing increases in plasma lipids and/or increasing risk for life-threatening ventricular arrhythmias as a result of sodium channel blockade. In this review, we propose that this suite of pathophysiologic processes constitutes "The Epileptic Heart Syndrome." We further propose that this condition can be diagnosed using standard electrocardiography, echocardiography, and lipid panels. The ultimate goal of this syndromic approach is to evaluate cardiac risk in patients with chronic epilepsy and to promote improved diagnostic strategies to reduce premature cardiac death.
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BACKGROUND: Few small-sample studies have quantified the T-wave alternans (TWA) value by 24-hour ambulatory recordings or exercise stress tests in patients with long QT syndrome (LQTS). The cutoff point of TWA ≥47 µV was based on patients with myocardial infarction. In our study, we aimed to (1) evaluate the association of TWA with life-threatening arrhythmic events (LAEs); (2) compare the predictive model of LAEs according to the TWA value measured by 24-hour ambulatory recordings and exercise stress tests; and (3) propose a cutoff point for the high risk of LAEs in patients with LQTS. METHODS AND RESULTS: The study cohort included 110 patients with LQTS referred to our hospital, and the primary outcome was LAEs. Thirty-one patients with LQTS (31/110 [28.2%]) developed LAEs during the following 24 (12-47) months. Peak TWA value quantified from 12 leads by 24-hour ambulatory recordings in patients with LQTS with LAEs (LQTS-LAEs group) was significantly higher than LQTS without LAEs (LQTS-non-LAEs group) (64.0 [42.0-86.0] µV versus 43.0 [36.0-53.0] µV; P<0.01). There was no statistical difference in TWA value measured by exercise stress tests between the 2 groups (69.0 [54.5-127.5] µV versus 68.5 [53.3-99.8] µV; P=0.871). The new cutoff point of the peak TWA value measured by 24-hour ambulatory recordings was 55.5 µV, with a sensitivity of 75.0% and a specificity of 78.6%. A univariate Cox regression analysis revealed that TWA value ≥55.5 µV was a strong predictor of LAEs (hazard ratio [HR], 4.5 [2.1-9.6]; P<0.001]. A multivariate Cox regression analysis indicated that TWA value ≥55.5 µV remained significant (HR, 2.7 [1.1-6.8]; P=0.034). CONCLUSIONS: Peak TWA measured by 24-hour ambulatory recordings was a more favorable risk stratification marker than exercise stress tests for patients with LQTS.
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Electrocardiografía Ambulatoria , Prueba de Esfuerzo , Síndrome de QT Prolongado , Humanos , Femenino , Síndrome de QT Prolongado/diagnóstico , Síndrome de QT Prolongado/fisiopatología , Masculino , Prueba de Esfuerzo/métodos , Medición de Riesgo/métodos , Adulto , Electrocardiografía Ambulatoria/métodos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Factores de Riesgo , Adulto Joven , Pronóstico , Factores de Tiempo , Estudios Retrospectivos , Frecuencia Cardíaca/fisiologíaRESUMEN
INTRODUCTION: Numerous P-wave indices have been explored as biomarkers to assess atrial fibrillation (AF) risk and the impact of therapy with variable success. OBJECTIVE: We investigated the utility of P-wave alternans (PWA) to track the effects of pulmonary vein isolation (PVI) and to predict atrial arrhythmia recurrence. METHODS: This medical records study included patients who underwent PVI for AF ablation at our institution, along with 20 control subjects without AF or overt cardiovascular disease. PWA was assessed using novel artificial intelligence-enabled modified moving average (AI-MMA) algorithms. PWA was monitored from the 12-lead ECG at ~1 h before and ~16 h after PVI (n = 45) and at the 4- to 17-week clinically indicated follow-up visit (n = 30). The arrhythmia follow-up period was 955 ± 112 days. RESULTS: PVI acutely reduced PWA by 48%-63% (p < .05) to control ranges in leads II, III, aVF, the leads with the greatest sensitivity in monitoring PWA. Pre-ablation PWA was ~6 µV and decreased to ~3 µV following ablation. Patients who exhibited a rebound in PWA to pre-ablation levels at 4- to 17-week follow-up (p < .01) experienced recurrent atrial arrhythmias, whereas patients whose PWA remained reduced (p = .85) did not, resulting in a significant difference (p < .001) at follow-up. The AUC for PWA's prediction of first recurrence of atrial arrhythmia was 0.81 (p < .01) with 88% sensitivity and 82% specificity. Kaplan-Meier analysis estimated atrial arrhythmia-free survival (p < .01) with an adjusted hazard ratio of 3.4 (95% CI: 1.47-5.24, p < .02). CONCLUSION: A rebound in PWA to pre-ablation levels detected by AI-MMA in the 12-lead ECG at standard clinical follow-up predicts atrial arrhythmia recurrence.
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Potenciales de Acción , Fibrilación Atrial , Ablación por Catéter , Electrocardiografía , Frecuencia Cardíaca , Valor Predictivo de las Pruebas , Venas Pulmonares , Recurrencia , Humanos , Venas Pulmonares/cirugía , Venas Pulmonares/fisiopatología , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/cirugía , Fibrilación Atrial/diagnóstico , Masculino , Femenino , Ablación por Catéter/efectos adversos , Persona de Mediana Edad , Anciano , Factores de Tiempo , Resultado del Tratamiento , Factores de Riesgo , Estudios Retrospectivos , Estudios de Casos y ControlesRESUMEN
BACKGROUND: New methods to identify patients who benefit from a primary prophylactic implantable cardioverter-defibrillator (ICD) are needed. T-wave alternans (TWA) has been shown to associate with arrhythmogenesis of the heart and sudden cardiac death. We hypothesized that TWA might be associated with benefit from ICD implantation in primary prevention. METHODS AND RESULTS: In the EU-CERT-ICD (European Comparative Effectiveness Research to Assess the Use of Primary Prophylactic Implantable Cardioverter-Defibrillators) study, we prospectively enrolled 2327 candidates for primary prophylactic ICD. A 24-hour Holter monitor reading was taken from all recruited patients at enrollment. TWA was assessed from Holter monitoring using the modified moving average method. Study outcomes were all-cause death, appropriate shock, and survival benefit. TWA was assessed both as a contiguous variable and as a dichotomized variable with cutoff points <47 µV and <60 µV. The final cohort included 1734 valid T-wave alternans samples, 1211 patients with ICD, and 523 control patients with conservative treatment, with a mean follow-up time of 2.3 years. TWA ≥60 µV was a predicter for a higher all-cause death in patients with an ICD on the basis of a univariate Cox regression model (hazard ratio, 1.484 [95% CI, 1.024-2.151]; P=0.0374; concordance statistic, 0.51). In multivariable models, TWA was not prognostic of death or appropriate shocks in patients with an ICD. In addition, TWA was not prognostic of death in control patients. In a propensity score-adjusted Cox regression model, TWA was not a predictor of ICD benefit. CONCLUSIONS: T-wave alternans is poorly prognostic in patients with a primary prophylactic ICD. Although it may be prognostic of life-threatening arrhythmias and sudden cardiac death in several patient populations, it does not seem to be useful in assessing benefit from ICD therapy in primary prevention among patients with an ejection fraction of ≤35%.
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Muerte Súbita Cardíaca , Desfibriladores Implantables , Electrocardiografía Ambulatoria , Prevención Primaria , Humanos , Prevención Primaria/métodos , Masculino , Femenino , Muerte Súbita Cardíaca/prevención & control , Muerte Súbita Cardíaca/etiología , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Electrocardiografía Ambulatoria/métodos , Cardioversión Eléctrica/instrumentación , Cardioversión Eléctrica/efectos adversos , Medición de Riesgo/métodos , Factores de Riesgo , Arritmias Cardíacas/terapia , Arritmias Cardíacas/fisiopatología , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/prevención & control , Arritmias Cardíacas/mortalidad , Resultado del Tratamiento , Valor Predictivo de las Pruebas , Factores de Tiempo , Europa (Continente)/epidemiología , Pronóstico , Frecuencia Cardíaca/fisiologíaRESUMEN
BACKGROUND AND OBJECTIVE: T-wave alternans (TWA) is a fluctuation in the repolarization morphology of the ECG. It is associated with cardiac instability and sudden cardiac death risk. Diverse methods have been proposed for TWA analysis. However, TWA detection in ambulatory settings remains a challenge due to the absence of standardized evaluation metrics and detection thresholds. METHODS: In this work we use traditional TWA analysis signal processing-based methods for feature extraction, and two machine learning (ML) methods, namely, K-nearest-neighbor (KNN) and random forest (RF), for TWA detection, addressing hyper-parameter tuning and feature selection. The final goal is the detection in ambulatory recordings of short, non-sustained and sparse TWA events. RESULTS: We train ML methods to detect a wide variety of alternant voltage from 20 to 100 µV, i.e., ranging from non-visible micro-alternans to TWA of higher amplitudes, to recognize a wide range in concordance to risk stratification. In classification, RF outperforms significantly the recall in comparison with the signal processing methods, at the expense of a small lost in precision. Despite ambulatory detection stands for an imbalanced category context, the trained ML systems always outperform signal processing methods. CONCLUSIONS: We propose a comprehensive integration of multiple variables inspired by TWA signal processing methods to fed learning-based methods. ML models consistently outperform the best signal processing methods, yielding superior recall scores.
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Arritmias Cardíacas , Electrocardiografía Ambulatoria , Humanos , Electrocardiografía Ambulatoria/métodos , Frecuencia Cardíaca , Arritmias Cardíacas/diagnóstico , Muerte Súbita Cardíaca , Procesamiento de Señales Asistido por Computador , Electrocardiografía/métodosRESUMEN
High levels of T-wave alternans (TWA) are linked to an increased risk of sudden cardiac death. People with epilepsy display elevated TWA levels that are decreased by chronic vagus nerve stimulation via implanted devices after 2-4 weeks or later. Our objective was to explore short-term effects of transcutaneous auricular vagus nerve stimulation (tVNS) on TWA. Five patients (3 female) with focal epilepsy undergoing video-EEG monitoring were included. TWA levels were determined using a one-channel modified lead I ECG via an open-source TWA-algorithm on two consecutive days, 1 h before, during and after tVNS via the left auricle. Data are given as mean ± SE. Mean TWA at baseline was 3.8 ± 0.4 µV and 3.0 ± 0.6 µV during stimulation on day 2. Stimulations on the second day were associated with TWA reductions by 22 ± 13 % that exceeded stimulation effects on the first day relative to baseline (p < 0.05). Linear mixed-models revealed effects of both stimulation (p < 0.05) and stimulation number (p < 0.005). Normalized TWA showed reproducible peak reductions at both days within 35 min after the initiation of tVNS (p < 0.05). Our observations suggest that tVNS has short-term effects on TWA, supporting the notion that vagus nerve stimulation has a beneficial impact on electrical cardiac properties.
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Objectives: Heart rate turbulence (HRT) and T-wave alternans (TWA), non-invasive markers of cardiac autonomic dysfunction, and ventricular repolarization abnormality, reportedly, predict the risk of cardiovascular death after myocardial infarction. We investigated whether pre-operative assessment of HRT and/or TWA could predict long-term mortality following coronary artery bypass graft (CABG) surgery. Methods: From May 2010 to December 2017, patients undergoing elective CABG and receiving 24 h ambulatory electrocardiogram monitoring 1 to 5 days prior to CABG surgery were prospectively enrolled. Pre-operative HRT and TWA were measured using a 24 h ambulatory electrocardiogram. The relative risk of cardiac or overall death was assessed according to abnormalities of HRT, TWA, or left ventricular ejection fraction (LV EF). Results: During the mean follow-up period of 4.6 ± 3.9 years, 40 adjudicated overall (5.9%/yr) and 5 cardiac deaths (0.9%/yr) occurred in 146 enrolled patients (64.9 ± 9.3 years; 108 males). Patients with abnormal HRT exhibited significantly higher relative risks of cardiac death (adjusted hazard ratio [HR] 24.9, 95% confidence interval [CI] 1.46-427) and all-cause death (adjusted HR 5.77, 95% CI 2.34-14.2) compared to those with normal HRT. Moreover, abnormal HRT plus abnormal TWA and LV EF < 50% was associated with a greater elevation in cardiac and overall mortality risk. The predictive role of abnormal HRT with/without abnormal TWA for all-cause death was likely more prominent in patients with mildly reduced (35 to 50%) or preserved (≥50%) LV EF. Abnormal HRT plus abnormal TWA and LV EF < 50% showed high negative predictive value in cardiac and overall mortality risk. Conclusions: Assessment of pre-operative HRT and/or TWA predicted mortality risk in patients undergoing elective CABG. Combined analysis of HRT, TWA, and LVEF enhanced the prognostic power. In particular, the predictive value of HRT was enhanced in patients with preserved or mid-range LV EF.
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T-wave alternans (TWA) has been used for predicting the risk of malignant cardiac arrhythmias and sudden cardiac death (SCD) in multiple clinical settings; however, possible mechanism(s) underlying the spontaneous transition from cellular alternans reflected by TWA to arrhythmias in impaired repolarization remains unclear. The healthy guinea pig ventricular myocytes under E-4031 blocking IKr (0.1 µM, N = 12; 0.3 µM, N = 10; 1 µM, N = 10) were evaluated using whole-cell patch-clamp. The electrophysiological properties of isolated perfused guinea pig hearts under E-4031 (0.1 µM, N = 5; 0.3 µM, N = 5; 1 µM, N = 5) were evaluated using dual- optical mapping. The amplitude/threshold/restitution curves of action potential duration (APD) alternans and potential mechanism(s) underlying the spontaneous transition of cellular alternans to ventricular fibrillation (VF) were examined. There were longer APD80 and increased amplitude and threshold of APD alternans in E-4031 group compared with baseline group, which was reflected by more pronounced arrhythmogenesis at the tissue level, and were associated with steep restitution curves of the APD and the conduction velocity (CV). Conduction of AP alternans augmented tissue's functional spatiotemporal heterogeneity of regional AP/Ca alternans, as well as the AP/Ca dispersion, leading to localized uni-directional conduction block that spontaneous facilitated the formation of reentrant excitation waves without the need for additional premature stimulus. Our results provide a possible mechanism for the spontaneous transition from cardiac electrical alternans in cellular action potentials and intercellular conduction without the involvement of premature excitations, and explain the increased susceptibility to ventricular arrhythmias in impaired repolarization. In this study, we implemented voltage-clamp and dual-optical mapping approaches to investigate the underlying mechanism(s) for the arrhythmogenesis of cardiac alternans in the guinea pig heart at cellular and tissue levels. Our results demonstrated a spontaneous development of reentry from cellular alternans, arising from a combined actions of restitution properties of action potential duration, conduction velocity of excitation wave and interplay between alternants of action potential and the intracellular Ca handling. We believe this study provides new insights into underlying the mechanism, by which cellular cardiac alternans spontaneously evolves into cardiac arrhythmias.
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Nacimiento Prematuro , Fibrilación Ventricular , Animales , Cobayas , Femenino , Humanos , Arritmias Cardíacas , Miocitos Cardíacos , Muerte Súbita Cardíaca , Potenciales de AcciónRESUMEN
Here, we report a rare case of a three-year-old boy with Jervell and Lange-Nielsen (JLN) syndrome who presented with two episodes of nocturnal agonal gasp provoked by fever mimicking syncope in the last six months with a history of sudden cardiac death in one elderly sibling. Interestingly, an electrocardiogram (EKG) revealed macro T-wave alternans (TWA) indicative of a high risk of malignant ventricular arrhythmia in the form of ventricular fibrillation and sudden cardiac death. TWA in JLN syndrome has not been described in the global literature so far. Our case is unique and the first to describe macro TWA in JLN syndrome and is a teaching point to young cardiologists to always look for macro TWA in the EKG of long QT syndrome for risk stratification, management, and, most importantly, avoiding the risk of sudden cardiac death.
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Background: Cardiac arrhythmias are significantly associated with poor outcomes in coronavirus disease 2019 (COVID-19) patients. Microvolt T-wave alternans (TWA) can be automatically quantified and has been recognized as a representation of repolarization heterogeneity and linked to arrhythmogenesis in various cardiovascular diseases. This study aimed to explore the correlation between microvolt TWA and COVID-19 pathology. Methods: Patients suspected of COVID-19 in Mohammad Hoesin General Hospital were consecutively evaluated using Alivecor® Kardiamobile 6L™ portable electrocardiogram (ECG) device. Severe COVID-19 patients or those who are unable to cooperate in active ECG self-recording were excluded from the study. TWA was detected and its amplitude was quantified using the novel enhanced adaptive match filter (EAMF) method. Results: A total of 175 patients, 114 COVID-19 patients (polymerase chain reaction (PCR)-positive group), and 61 non-COVID-19 patients (PCR-negative group) were enrolled in the study. PCR-positive group was subdivided according to the severity of COVID-19 pathology into mild and moderate severity subgroups. Baseline TWA levels were similar between both groups during admission (42.47 ± 26.52 µV vs. 44.72 ± 38.21 µV), but higher TWA levels were observed during discharge in the PCR-positive compared to the PCR-negative group (53.45 ± 34.42 µV vs. 25.15 ± 17.64 µV, P = 0.03). The correlation between PCR-positive result in COVID-19 and TWA value was significant, after adjustment of other confounding variables (R2 = 0.081, P = 0.030). There was no significant difference in TWA levels between mild and moderate severity subgroups in patients with COVID-19, both during admission (44.29 ± 27.14 µV vs. 36.75 ± 24.46 µV, P = 0.34) and discharge (49.47 ± 33.62 µV vs. 61.09 ± 35.99 µV, P = 0.33). Conclusions: Higher TWA values can be observed on follow-up ECG obtained during discharge in the PCR-positive COVID-19 patients.
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BACKGROUND: Autonomic regulation therapy (ART) utilizing cervical vagus nerve stimulation (VNS) appeared to be safe and to improve autonomic tone, symptoms, and cardiac mechanical function in patients with symptomatic heart failure and reduced ejection fraction in the ANTHEM-HF Study. The ANTHEM-HFpEF Study is the first investigation to evaluate the safety and feasibility of ART in patients with symptomatic heart failure and preserved or mildly reduced ejection fraction (HFpEF, HFmrEF). METHODS: This open-label interventional study enrolled 52 patients with HFpEF or HFmrEF, NYHA Class II-III, and LVEF ≥40%, who received stable guideline-directed medical therapy. All patients were successfully implanted with LivaNova VNS Therapy® system with an electrical lead surrounding the right cervical vagus nerve. RESULTS: Adverse event incidence was low. At 12 months, NYHA class (p <0.0001), 6-min walk distance (p <0.05), and quality of life (p <0.0001) were improved. Cardiac mechanical function measures were normal at baseline, except for left ventricular mass index in women and E/e' ratio in all patients, which were elevated at baseline, and were unchanged by ART. Autonomic tone and reflexes improved, indicated by 29% decrease in low-frequency/high-frequency heart rate variability to normal levels (p = 0.028) and by increased heart rate turbulence slope (p = 0.047). T-wave alternans (p = 0.001) and T-wave heterogeneity (p = 0.001) were reduced from abnormal to normal ranges. Nonsustained ventricular tachycardia incidence decreased (p = 0.027). CONCLUSIONS: ART appeared well-tolerated and safe in patients with HFpEF or HFmrEF. Chronic ART did not alter mechanical function measures but was associated with improved heart failure symptoms, exercise tolerance, autonomic tone, and cardiac electrical stability. CLINICAL TRIAL REGISTRY: Autonomic Neural Regulation Therapy to Enhance Myocardial Function in Heart Failure with Preserved Ejection Fraction [ClinicalTrials.gov #NCT03163030, registered 05/22/2017].
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Cardiopatías , Insuficiencia Cardíaca , Disfunción Ventricular Izquierda , Femenino , Humanos , Arritmias Cardíacas , Enfermedad Crónica , Corazón , Insuficiencia Cardíaca/terapia , Insuficiencia Cardíaca/tratamiento farmacológico , Pronóstico , Calidad de Vida , Volumen Sistólico/fisiología , Resultado del Tratamiento , Función Ventricular Izquierda/fisiologíaRESUMEN
BACKGROUND: Sudden cardiac death (SCD) risk is elevated following acute myocardial infarction (MI). The time course of SCD susceptibility post-MI requires further investigation. METHODS: In this observational cohort study, we employed state-of-the-art noninvasive ECG techniques to track the daily time course of cardiac electrical instability and autonomic function following ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI). Preventice BodyGuardian MINI-EL Holters continuously recorded ECGs for 7 days at hospital discharge and at 40 days for STEMI (N = 5) or at 90 days for NSTEMI patients (N = 5). Cardiac electrical instability was assessed by T-wave alternans (TWA) and T-wave heterogeneity (TWH); autonomic tone was determined by rMSSD-heart rate variability (HRV). RESULTS: TWA was severely elevated (≥60 µV) in STEMI patients (80 ± 10.3 µV) at discharge and throughout the first recording period but declined by 50% to 40 ± 2.3 µV (p = .03) by Day 40 and remained in the normal range (<47 µV). TWH, a related phenomenon analyzed from 12-lead ECGs, was reduced by 63% in the five STEMI patients from discharge to normal (<80 µV) at follow-up (105 ± 27.3 to 39 ± 3.3 µV, p < .04) but increased by 65% in a STEMI case (89 to 147 µV), who received a wearable defibrillator vest and later implantable cardioverter defibrillator. In NSTEMI patients, TWA was borderline abnormal (47 ± 3.3 µV) at discharge and declined by 19% to normal (38 ± 1.2 µV) by Day 90 (p = .05). An overall reciprocal increase in rMSSD-HRV suggested recovery of vagal tone. CONCLUSIONS: This study provides proof-of-principle for tracking post-MI SCD risk in individual patients with implications for personalized therapy.
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Infarto del Miocardio , Infarto del Miocardio sin Elevación del ST , Infarto del Miocardio con Elevación del ST , Humanos , Electrocardiografía , Infarto del Miocardio/complicaciones , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/terapia , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/etiología , Electrocardiografía Ambulatoria , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/prevención & control , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/terapia , SíndromeRESUMEN
Background and objective: T-wave alternans (TWA) is a fluctuation of the ST-T complex of the surface electrocardiogram (ECG) on an every-other-beat basis. It has been shown to be clinically helpful for sudden cardiac death stratification, though the lack of a gold standard to benchmark detection methods limits its application and impairs the development of alternative techniques. In this work, a novel approach based on machine learning for TWA detection is proposed. Additionally, a complete experimental setup is presented for TWA detection methods benchmarking. Methods: The proposed experimental setup is based on the use of open-source databases to enable experiment replication and the use of real ECG signals with added TWA episodes. Also, intra-patient overfitting and class imbalance have been carefully avoided. The Spectral Method (SM), the Modified Moving Average Method (MMA), and the Time Domain Method (TM) are used to obtain input features to the Machine Learning (ML) algorithms, namely, K Nearest Neighbor, Decision Trees, Random Forest, Support Vector Machine and Multi-Layer Perceptron. Results: There were not found large differences in the performance of the different ML algorithms. Decision Trees showed the best overall performance (accuracy 0.88 ± 0.04 , precision 0.89 ± 0.05 , Recall 0.90 ± 0.05 , F1 score 0.89 ± 0.03 ). Compared to the SM (accuracy 0.79, precision 0.93, Recall 0.64, F1 score 0.76) there was an improvement in every metric except for the precision. Conclusions: In this work, a realistic database to test the presence of TWA using ML algorithms was assembled. The ML algorithms overall outperformed the SM used as a gold standard. Learning from data to identify alternans elicits a substantial detection growth at the expense of a small increment of the false alarm.
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BACKGROUND: Macroscopic T wave alternans (macro-TWA) often heralds the onset of Torsades de Pointes in patients with QT prolongation. However, the mechanisms underlying macro-TWA remain unclear. We examined the cellular and ionic basis for macro-TWA in rabbits with left ventricular hypertrophy (LVH). METHODS: The renovascular hypertension model was used to induce LVH in rabbits. Action potentials were simultaneously recorded from epicardium and endocardium together with a transmural ECG and isometric contractility in arterially perfused left ventricular wedges. Late sodium current (INa-L) was recorded in single-isolated left ventricular myocytes with the whole cell patch-clamp technique. RESULTS: Macro-TWA and accompanied mechanical alternans occurred spontaneously in 8 of 33 LVH rabbits (P<0.05, versus 0/15 in controls) and were induced by an INa-L enhancer ATX-II at 1 to 3 nM in additional 7. Macro-TWA and mechanical alternans occurred discordantly, that is, that longer QT interval and larger T wave were associated with weaker isometric contvractility. Alternating early afterdepolarizations in the endocardium caused macro-TWA in 12 of 15 LVH rabbits and, therefore, early afterdepolarization-dependent R-from-T extrasystoles and Torsades de Pointes always originated from the beats with longer QT and larger T wave during macro-TWA. INa-L density was significantly larger in LVH myocytes than that of control myocytes. Macro-TWA, mechanical alternans, R-from-T extrasystoles, and Torsades de Pointes were all abolished by INa-L blocker ranolazine or mexiletine. CONCLUSIONS: LVH enhances INa-L density and promotes alternating early afterdepolarizations in the left ventricular endocardium that manifest as macro-TWA with discordant mechanical alternans. INa-L blockade abolishes macro-TWA, mechanical alternans, early afterdepolarization-dependent R-from-T extrasystoles, and Torsades de Pointes.
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Síndrome de QT Prolongado , Torsades de Pointes , Animales , Conejos , Bradicardia , Arritmias Cardíacas , Ventrículos Cardíacos , Síndrome de QT Prolongado/diagnóstico , Complejos Cardíacos Prematuros/complicaciones , Electrocardiografía , Potenciales de Acción/fisiologíaRESUMEN
PURPOSE: Drug-induced type I Brugada syndrome (BrS) is associated with a ventricular arrhythmia (VA) rate of 1 case per 100 person-years. This study aims to evaluate changes in electrocardiographic (ECG) parameters such as microvolt T wave alternans (mTWA) and heart rate variability (HRV) at baseline and during ajmaline testing for BrS diagnosis. METHODS: Consecutive patients diagnosed with BrS during ajmaline testing with 5-year follow-up were included in this study. For comparison, a negative ajmaline control group and an isoproterenol control group were also included. ECG recordings during ajmaline or isoproterenol test were divided in two timeframes from which ECG parameters were calculated: a 5-min baseline timeframe and a 5-min drug timeframe. RESULTS: A total of 308 patients with BrS were included, 22 (0.7%) of which suffered VAs during follow-up. One hundred patients were included in both isoproterenol and negative ajmaline control groups. At baseline, there was no difference in ECG parameters between control groups and patients with BrS, nor between BrS with and without VAs. During ajmaline testing, BrS with VAs presented longer QRS duration [159 ± 34 ms versus 138 (122-155) ms, p = 0.006], higher maximum mTWA [33.8 (14.0-114) µV versus 8.00 (3.67-28.2) µV, p = 0.001], and lower power in low frequency band [25.6 (5.8-53.8) ms2 versus 129.5 (52.7-286) ms2, p < 0.0001] when compared to BrS without VAs. CONCLUSIONS: Ajmaline induced important HRV changes similar to those observed during isoproterenol. Increased mTWA was observed only in patients with BrS. BrS with VAs during follow-up presented worse changes during ajmaline test, including lower LF power and higher maximum mTWA which were independent predictors of events.
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Ajmalina , Síndrome de Brugada , Humanos , Ajmalina/farmacología , Síndrome de Brugada/diagnóstico , Frecuencia Cardíaca , Isoproterenol , Arritmias Cardíacas , Electrocardiografía , PronósticoRESUMEN
Despite early repolarization (ER) syndrome being usually considered benign, its association with severe/malignant ventricular arrhythmias (VA) was also reported. Microvolt T-wave alternans (MTWA) is an electrocardiographic marker for the development of VA, but its role in ER syndrome remains unknown. A 90-second 6-lead electrocardiogram from an ER syndrome patient, acquired with the Kardia recorder, was analyzed by the enhanced adaptive matched filter for MTWA quantification. On average, MTWA was 50 µV, higher than what was previously observed on healthy subjects using the same method. In our ER syndrome patient, MTWA plays a potential role in VA development in ER syndrome.