Dual assessment of abnormal cardiac electrical dispersion and diastolic dysfunction for early detection of the epileptic heart condition.

BACKGROUND: People with epilepsy (PWE) are at increased risk for premature death due to many factors. Sudden unexpected death in epilepsy (SUDEP) is among the most important causes of death in these individuals and possibly, sudden cardiac death (SCD) in epilepsy is also as important. The possibility of concurrent derangement in electrical and mechanical cardiac function, which could be a marker of early cardiac involvement in PWE, has not been investigated in that population. METHODS: Electrical dispersion indices (T-wave peak to T-wave end, TpTe; QT dispersion, QTd; QT interval corrected for heart rate, QTc) were analyzed in patients with pharmacoresistant temporal lobe epilepsy and compared to a control group. The electromechanical relationship between those indices and echocardiographic parameters were further assessed in PWE. RESULTS: In 19 PWE and 21 controls, we found greater TpTe and QTd in PWE (TpTe: 91.6 ± 16.4 ms vs. 65.2 ± 12.1 ms, p < 0.0001; and QTd: 45.3 ± 13.1 ms vs. 19 ± 6.2 ms, p < 0.0001, respectively). QTc was similar between PWE and controls (419.2 ± 31.4 ms vs. 435.1 ± 31.4 ms, p = 0.12). In multivariate linear regression, TpTe, QTc, and epilepsy duration were related to left ventricular mass; QTc was associated with left atrial volume; QTc, the number of seizures per month, epilepsy duration and antiseizure medication explained 81% of E/A mitral wave Doppler ratio. CONCLUSIONS: This is the first report to demonstrate concurrent electrical dispersion and diastolic dysfunction in PWE. These noninvasive biomarkers could prove useful in early detection of the "Epileptic Heart" condition.

Spectrum of clinical applications of interlead ECG heterogeneity assessment: From myocardial ischemia detection to sudden cardiac death risk stratification.

Heterogeneity in depolarization and repolarization among regions of cardiac cells has long been recognized as a major factor in cardiac arrhythmogenesis. This fundamental principle has motivated development of noninvasive techniques for quantification of heterogeneity using the surface electrocardiogram (ECG). The initial approaches focused on interval analysis such as interlead QT dispersion and Tpeak -Tend difference. However, because of inherent difficulties in measuring the termination point of the T wave and commonly encountered irregularities in the apex of the T wave, additional techniques have been pursued. The newer methods incorporate assessment of the entire morphology of the T wave and in some cases of the R wave as well. This goal has been accomplished using a number of promising vectorial approaches with the resting 12-lead ECG. An important limitation of vectorcardiographic analyses is that they require exquisite stability of the recordings and are not inherently suitable for use in exercise tolerance testing (ETT) and/or ambulatory ECG monitoring for provocative stress testing or evaluation of the influence of daily activities on cardiac electrical instability. The objectives of the present review are to describe a technique that has been under clinical evaluation for nearly a decade, termed "interlead ECG heterogeneity." Preclinical testing data will be briefly reviewed. We will discuss the main clinical findings with regard to sudden cardiac death risk stratification, heart failure evaluation, and myocardial ischemia detection using standard recording platforms including resting 12-lead ECG, ambulatory ECG monitoring, ETT, and pharmacologic stress testing in conjunction with single-photon emission computed tomography myocardial perfusion imaging.

Quantitative T-wave alternans analysis for sudden cardiac death risk assessment and guiding therapy: answered and unanswered questions: For: Proceedings of ICE2015 Comandatuba, Brazil, Sudden Death Symposium.

This review addresses current questions regarding use of T-wave alternans to stratify risk for sudden cardiac death. Both of the currently available commercial methodologies, namely, the frequency-domain spectral method and the time-domain modified moving average (MMA) method, are supported by guideline statements, cleared by the US FDA, and covered by the US Center for Medicare and Medicaid services. Similar numbers of patients have been enrolled in predictive studies; odds ratios generated by the two methods are similar including in a head-to-head study. However, in two prospective studies, prediction by TWA with the spectral method was negative, likely due to withdrawal of beta-blockade before the test with later resumption, while all studies with MMA have achieved prediction when the commercial software was used appropriately. Questions currently undergoing investigation include TWA's potential to guide ICD implantation, to track changes in risk during cardiac disease progression, and to evaluate the adequacy of medical therapy.

Multilead template-derived residua of surface ECGS for quantitative assessment of arrhythmia risk.

BACKGROUND: Contemporary electrocardiographic (ECG) markers including ventricular ectopy and arrhythmias have not proved reliable in risk assessment for life-threatening arrhythmias. METHODS: We developed the "Multilead ECG Template-Derived Residua" approach to remove intrinsic morphologic differences and allow calculation of pathologic ECG heterogeneities among spatially separated leads. Prediction by R-wave and T-wave heterogeneity (RWH, TWH) analysis was tested in simulated and clinical ECGs. RESULTS: An enabling description of the Residua algorithm is provided. Simulated ECGs with but not without Residua produced a linear relationship (correlation coefficient r(2) = 0.999) between input and output RWH and TWH values. In heart failure patients, Residua disclosed a marked crescendo in RWH from 164.1 ± 33.1 at baseline to 299.8 ± 54.5 µV and TWH from 134.5 ± 20.6 at baseline to 239.2 ± 37.0 µV at 30-45 minutes before the arrhythmia (both, P < 0.05), which remained elevated until arrhythmia onset. Without Residua, mean RWH and TWH were elevated at 1061.0 ± 222.9 and 882.5 ± 375.2 µV, respectively, throughout the recording and were not different prior to ventricular tachycardia onset. CONCLUSIONS: Calculation of ECG-template derived Residua provides a highly accurate means for assessing arrhythmia risk from standard ECGs. Potential widespread applications include resting diagnostic 12-lead, ambulatory, and exercise ECGs, electrophysiologic study laboratory recordings, and implantable devices.

Ambulatory ECG-based T-wave alternans monitoring for risk assessment and guiding medical therapy: mechanisms and clinical applications.

Identification of individuals at risk for sudden cardiac death (SCD), the main cause of adult mortality in developed countries, remains a major challenge. The main contemporary noninvasive marker, left ventricular ejection fraction (LVEF), has not proved adequately reliable, as the majority of individuals who die suddenly have relatively preserved cardiac mechanical function. Monitoring of T-wave alternans (TWA), a beat-to-beat fluctuation in ST-segment or T-wave morphology, on ambulatory electrocardiogram (AECG) is an attractive approach on both scientific and clinical grounds. Specifically, TWA's capacity to assess risk for malignant arrhythmias has been shown to rest on sound electrophysiologic principles and AECG-based TWA monitoring can be performed in the flow of routine clinical evaluation. This review addresses: (1) electrophysiologic and ionic mechanisms underlying TWA's predictivity, (2) principles and practical aspects of AECG-based TWA monitoring, (3) clinical evidence supporting this approach to SCD risk stratification, and (4) current and potential applications in guiding medical therapy.

Atrioventricular conduction and cardiovascular mortality: assessment of recovery PR interval is superior to pre-exercise measurement.

BACKGROUND: A prolonged electrocardiographic PR interval at rest has been considered a benign phenomenon until recently. OBJECTIVE: We hypothesized that measurement of the PR interval during recovery from physical exertion could improve cardiovascular mortality risk stratification because it would track the dynamic influences of homeostatic mechanisms controlling atrioventricular (AV) conduction. METHODS: A total of 1,979 consecutive patients (1,244 men and 735 women) with clinically indicated bicycle ergometer tests enrolled in FINCAVAS (the Finnish Cardiovascular Study) were included in the study. The PR interval was measured at 1 min before and at 2 min after exercise. RESULTS: During the mean follow-up period of 47 months (interquartile range: 37 to 59 months), 50 cardiovascular deaths (end point) were registered. The unadjusted hazard ratios (HR) in Cox regression analyses were significant for both continuous PR interval and first-degree atrioventricular (AV) block for pre- and post-exercise phases. After adjustment for standard markers, the PR interval for 20-ms increments (HR: 1.17, P = .117) and first-degree AV block (HR: 1.85, P = .138) during the pre-exercise phase were not prognostic. However, during recovery from exercise, prolonged AV conduction achieved significance both in continuous (HR: 1.29, P = .006) and dichotomized analyses (HR: 2.41, P = .045). CONCLUSION: The PR interval before exercise is not a robust risk stratifier for cardiovascular death during 4-year follow-up. Post-exercise assessment of AV conduction may offer improved prediction because of functional abnormalities that become manifest only during this physiologic challenge to the heart.

Combined assessment of heart rate recovery and T-wave alternans during routine exercise testing improves prediction of total and cardiovascular mortality: the Finnish Cardiovascular Study.

BACKGROUND: Identification of individuals who are at risk for cardiovascular death remains a pressing public health challenge. Derangements in autonomic function acting upon an electrically unstable substrate are thought to be critical elements in triggering cardiovascular events. OBJECTIVE: The purpose of this study was to analyze heart rate recovery (HRR) in combination with T-wave alternans (TWA) to improve risk assessment. METHODS: The Finnish Cardiovascular Study (FINCAVAS) enrolled consecutive patients (N = 1,972 [1,254 men and 718 women], age 57 +/- 13 years [mean +/- SD]) with a clinically indicated exercise test using bicycle ergometer. TWA was analyzed continuously with the time-domain modified moving average method. Maximum TWA at heart rates <125 bpm was derived. RESULTS: During 48 +/- 13 months of follow-up (mean +/- SD), 116 patients died; 55 deaths were cardiovascular. In multivariable Cox analysis after adjustment for common coronary risk factors, high exercise-based TWA (> or =60 microV) and low HRR (< or =18 bpm) yielded relative risks for all-cause mortality of 5.0 (95% confidence 2.1-12.1, P <.01) and for cardiovascular mortality of 12.3 (95% confidence interval 4.3-35.3, P <.01). High recovery-based TWA (> or =60 microV) and low HRR (< or =18 bpm) yielded relative risks for all-cause death of 6.1 (95% confidence interval 2.8-13.2, P <.01) and for cardiovascular mortality of 8.0 (95% confidence interval 2.9-22.0, P <.01). Prediction by HRR and TWA, both singly and in combination, exceeded that of standard cardiovascular risk factors. CONCLUSION: Reduced HRR and heightened TWA powerfully predict risk for cardiovascular and all-cause death in a low-risk population. This novel approach could aid in screening of general populations during routine exercise protocols as well as improve insights into pathophysiology.

Ambulatory ECG monitoring of T-wave alternans for arrhythmia risk assessment.

Experimental and clinical studies indicate a basic linkage between T-wave alternans (TWA) and susceptibility to malignant arrhythmias. In a variety of clinical populations with elevated risk of ventricular tachyarrhythmias, Fast Fourier Transform (FFT)-based assessment of TWA during fixed-rate atrial pacing or bicycle ergometry has shown predictive ability for arrhythmic events. However, after more than a decade since the introduction of TWA testing in human subjects, few studies have explored its utility in ambulatory ECG (AECG) recordings. This gap probably relates to major technical obstacles associated with monitoring of ambulatory subjects, including motion artifact and the requirement of data stationarity, which mandates fixing heart rate. To circumvent these difficulties, we devised a time-domain method, "Modified Moving Average Beat Analysis" (MMA) to determine TWA level accurately in freely moving subjects. Recently, MMA analysis was employed to analyze ambulatory ECG (AECG) records of post-myocardial infarction patients who were were at low risk of arrhythmic death. An increased risk of arrhythmic death was predicted by TWA level above the 75th percentile of controls (p<.05). Thus, the predictive power of TWA obtained with MMA analysis from AECG records obtained appears promising.

Optimizing ambulatory ECG monitoring of T-wave alternans for arrhythmia risk assessment.

Considerable scientific data support the potential value of T-wave alternans (TWA) as an index of vulnerability to ventricular fibrillation. This chapter summarizes our state of knowledge regarding the use of routine ambulatory ECGs to evaluate TWA and discusses recent methodologic approaches designed to optimize AECG-based TWA analysis for arrhythmia risk stratification. Newer methods, including the nonspectral technique of Modified Moving Average analysis, appear promising in detecting TWA during the changing conditions associated with daily activities. The Modified Moving Average approach does not require specialized electrodes and is not encumbered by the need to achieve target heart rates, as is the case for conventional spectral-based methods. Guidelines are provided for evaluating latent cardiac electrical instability using AECG-based TWA testing. These recent developments make possible the TWA analysis of ambulatory ECGs not only in prospective trials but also in vast stores of archival data.