Unexpected pericardial effusions are often found by frontline providers who perform computed tomography. To study the hypothesis that electrocardiographic findings and whether cancer is known or suspected importantly change the likelihood of tamponade for such providers, all unique patients with moderate or large pericardial effusions determined by transthoracic echocardiography during a 6-year period were retrospectively identified. Electrocardiograms were evaluated by blinded investigators for electrical alternans (total and QRS), low voltage (limb leads only, precordial leads only, and both), and tachycardia (>100 QRS complexes/min). Medical records were reviewed to determine whether cancer was known or suspected and whether tamponade was diagnosed. Tamponade was present in 66 patients (27% of 241) with moderate or large pericardial effusions. No tachycardia lowered the odds of tamponade the most (likelihood ratio 0.4, 95% confidence interval 0.3 to 0.6) but by a degree less than any single diagnostic element increased it when present. The combined presence of all 3 electrocardiographic findings and cancer increased the odds of tamponade 63-fold (likelihood ratio 63, 95% confidence interval 33 to 150), whereas their combined absence decreased the odds only fivefold (likelihood ratio 0.2, 95% confidence interval 0.2 to 0.3). In conclusion, electrocardiography findings and cancer rule in tamponade better than they rule it out. Combining these diagnostic elements improves their discriminatory power but not sufficiently enough to rule out tamponade in patients with moderate or large pericardial effusions.

Electrical alternans is a broad term that describes alternate-beat variation in the direction, amplitude and duration of any component of the ECG wave-form. It is associated with cardiac tamponade, serious ventricular arrhythmias, and sudden death. We present the clinical case of a 77-year-old female with electrical alternans, from which a diagnosis of cardiac tamponade was established.

Pulmonary hypertension provokes right heart failure and arrhythmias. Better understanding of the mechanisms underlying these arrhythmias is needed to facilitate new therapeutic approaches for the hypertensive, failing right ventricle (RV). The aim of our study was to identify the mechanisms generating arrhythmias in a model of RV failure induced by pulmonary hypertension. Rats were injected with monocrotaline to induce either RV hypertrophy or failure or with saline (control). ECGs were measured in conscious, unrestrained animals by telemetry. In isolated hearts, electrical activity was measured by optical mapping and myofiber orientation by diffusion tensor-MRI. Sarcoplasmic reticular Ca(2+) handling was studied in single myocytes. Compared with control animals, the T-wave of the ECG was prolonged and in three of seven heart failure animals, prominent T-wave alternans occurred. Discordant action potential (AP) alternans occurred in isolated failing hearts and Ca(2+) transient alternans in failing myocytes. In failing hearts, AP duration and dispersion were increased; conduction velocity and AP restitution were steeper. The latter was intrinsic to failing single myocytes. Failing hearts had greater fiber angle disarray; this correlated with AP duration. Failing myocytes had reduced sarco(endo)plasmic reticular Ca(2+)-ATPase activity, increased sarcoplasmic reticular Ca(2+)-release fraction, and increased Ca(2+) spark leak. In hypertrophied hearts and myocytes, dysfunctional adaptation had begun, but alternans did not develop. We conclude that increased electrical and structural heterogeneity and dysfunctional sarcoplasmic reticular Ca(2+) handling increased the probability of alternans, a proarrhythmic predictor of sudden cardiac death. These mechanisms are potential therapeutic targets for the correction of arrhythmias in hypertensive, failing RVs.

A critical need exists for reliable warning markers of in-hospital life-threatening arrhythmias. We used a new quantitative method to track interlead heterogeneity of depolarization and repolarization to detect premonitory changes before ventricular tachycardia (VT) in hospitalized patients with acute decompensated heart failure.Ambulatory ECGs (leads V(1), V(5), and aVF) recorded before initiation of drug therapy from patients enrolled in the PRECEDENT (Prospective Randomized Evaluation of Cardiac Ectopy with Dobutamine or Nesiritide Therapy) trial were analyzed. R-wave heterogeneity (RWH) and T-wave heterogeneity (TWH) were assessed by second central moment analysis and T-wave alternans (TWA) by modified moving average analysis. Of 44 patients studied, 22 had experienced episodes of VT (≥4 beats at heart rates >100 beats/min) following ≥120 minutes of stable sinus rhythm, and 22 were age- and sex-matched patients without VT. TWA increased from 18.6±2.1 μV (baseline, mean±SEM) to 27.9±4.6 μV in lead V(5) at 15 to 30 minutes before VT (P<0.05) and remained elevated until the arrhythmia occurred. TWA results in leads V(1) and aVF were similar. RWH and TWH were elevated from 164.1±33.1 and 134.5±20.6 μV (baseline) to 299.8±54.5 and 239.2±37.0 μV at 30 to 45 minutes before VT (P<0.05), respectively, preceding the crescendo in TWA by 15 minutes. Matched patients without VT did not display elevated RWH (185.5±29.4 μV) or TWH (157.1±27.2 μV) during the 24-hour period.This investigation is the first clinical demonstration of the potential utility of tracking depolarization and repolarization heterogeneity to detect crescendos in electrical instability that could forewarn of impending nonsustained VT. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00270400.

T-wave alternans (TWA) has been associated with increased vulnerability to ventricular tachyarrhythmias and sudden cardiac death. However, both random (white) noise and (patho)physiologic processes (ie, premature ventricular contractions and heart and respiration rates) may hamper TWA estimation and therefore lessen its clinical utility for risk stratification.To investigate the effect of random noise and certain (patho)physiologic processes on the estimation of TWA by using the fast Fourier transform method and to develop methods to overcome these potential sources of error.We used a combination of human electrocardiogram data and computer simulations to assess the effects of a premature ventricular contraction and random and colored noise on the accuracy of TWA estimation.We quantitatively demonstrate that replacing a "bad" beat with an odd/even median beat is a more accurate approach than replacing it with the overall average or the overall median beat. We also show that phase resetting may have a significant effect on alternans estimation and that estimation of alternans by using frequencies >0.4922 cycles/beat in a 128-point fast Fourier transform provides the most accurate approach for estimating the alternans when phase resetting is likely to occur. In addition, our data demonstrate that the number of indeterminate TWA tests due to high levels of noise can be reduced when the alternans voltage exceeds a new higher threshold. Furthermore, the amplitude of random noise has a significant effect on alternans estimation and the alternans voltage threshold should be adjusted for noise levels >1.8 μV. Finally, we quantitatively demonstrate that colored noise may lead to a false-positive or a false-negative result. We propose methods to estimate the effect of these (patho)physiologic processes on the alternans estimation in order to determine whether a TWA test is likely to be a true positive or a true negative.This study introduces novel methods to overcome potential sources of error in the estimation of TWA. These methods may improve the utility of TWA either for ambulatory monitoring or for clinical risk stratification for ventricular arrhythmias and sudden cardiac death.

This review considers of modern concepts of microvolt T-wave alternans (TWA): its pathophysiological basis at cellular level, particulars of quantitative analysis of TWA, modulating effects of autonomic nervous system and drugs, prognostic efficacy in predicting susceptibility to ventricular arrhythmia in comparison with other modern prognostic factors of sudden cardiac death.

An association between heterogeneity of repolarization alternans (RA) and cardiac electrical instability has been reported. Characterization of RA in health and identification of physiological RA heterogeneity may help discrimination of abnormal RA cases more likely associated to arrhythmic events. Thus, aim of the present study was the identification of a physiological RA region in terms of mean temporal location (MRAD) with respect to the T apex, and mean amplitude (MRAA), by application of our heart-rate adaptive match filter method to clinical ECG recordings from 51 control healthy (CH) subjects and 43 acute myocardial infarction (AMI) patients. Results indicate that RA occurring within the first half of the T wave is dominant in both CH and AMI populations (74.5% and 53.5% of cases, respectively; P<0.05). Definition of physiological RA region in the MRAD vs. MRAA plane (-83 ms ≤ MRAD ≤ 23 ms, 0≤ MRAA ≤ 30 μV) provided 0% and 32.6% abnormal RA cases among the CH subjects and AMI patients, respectively. We conclude that myocardial infarction may associate with an RA occurring early (MRAD<-83 ms) or late (MRAD >23 ms) along the JT segment, in addition or in alternative to an abnormally high RA amplitude (MRAA >30 μV).

The present study aimed to assess whether there are differences in risk indicators for perpetuating ventricular tachyarrhythmias (pVT) and self-terminating ventricular tachyarrhythmias (stVT).Patients with acute myocardial infarction (AMI) and baseline left ventricular ejection fraction ≤ 40% (n = 292) received an implantable electrocardiogram loop recorder from 5 to 21 days after AMI and were followed up for 24 months to document arrhythmic events in the Cardiac Arrhythmias and Risk Stratification after Acute Myocardial Infarction (CARISMA) study. Several risk markers, such as the inducibility to sustained ventricular tachycardia during programmed electrical stimulation (PES), the signal-averaged ECG QRS duration (SAECG-QRS), heart rate variability (HRV) and turbulence (HRT), T-wave alternans, and non-sustained ventricular tachycardia on Holter were analysed at 6 weeks after the AMI. During the follow-up, 26 patients (9%) experienced an stVT (≥ 16 beats and < 30 s), and 21 patients (7%) a pVT. The occurrence of non-sustained ventricular tachycardia on Holter significantly predicted stVT [hazard ratio (HR) = 2.90, 1.26-6.67, 95% confidence interval (CI), P = 0.01], but not pVT during the follow-up. The inducibility during PES (HR = 5.02, 1.85-13.60, 95% CI, P = 0.001), SAECG-QRS ≥ 130 ms (HR = 8.73, 3.38-22.56, 95% CI, P < 0.001), the short-term scaling exponent HRV parameter ≤ 0.77 (HR = 5.65, 2.12-15.10, 95% CI, P = 0.001), and HRT slope ≤ 1.75 ms/NN (HR = 4.57, 1.80-11.59, 95% CI, P = 0.001) were significant predictors of pVT, even after adjustments with relevant clinical parameters (P from < 0.01 to < 0.001), but did not significantly predict the occurrence of stVT (P from 0.35 to 0.75).Self-terminating ventricular tachyarrhythmia and pVT have differences in electrophysiological substrate and arrhythmia modifiers in post-AMI patients with moderate left ventricular dysfunction.

Accurate recognition of individuals at higher immediate risk of sudden cardiac death (SCD) is still an open question. The fortuitous nature of acute cardiovascular events just does not seem to fit the well-known model of ventricular tachycardia/fibrillation induction in a static arrhythmogenic substrate by a synchronous trigger. On the mechanism of SCD, a dynamical electrical instability would better explain the rarity of the simultaneous association of a correct trigger and an appropriate cardiac substrate. Several studies have been conducted trying to measure this cardiac electrical instability (or any valid surrogate) in an ECG beat stream. Among the current possible candidates we can number QT prolongation, QT dispersion, late potentials, T-wave alternans (TWA), and heart rate turbulence. This article reviews the particular role of TWA in the current cardiac risk stratification scenario. TWA findings are still heterogeneous, ranging from very good to nearly null prognostic performance depending on the clinical population observed and clinical protocol in use. To fill the current gaps in the TWA base of knowledge, practitioners, and researchers should better explore the technical features of the several technologies available for TWA evaluation and pay greater attention to the fact that TWA values are responsive to several factors other than medications. Information about the cellular and subcellular mechanisms of TWA is outside the scope of this article, but the reader is referred to some of the good papers available on this topic whenever this extra information could help the understanding of the concepts and facts covered herein.

We sought to explore the distribution pattern of Na(+) channels across ventricular wall, and to determine its functional correlates, in the guinea pig heart. Voltage-dependent Na(+) channel (Na(v)) protein expression levels were measured in transmural samples of ventricular tissue by Western blotting. Isolated, perfused heart preparations were used to record monophasic action potentials and volume-conducted ECG, and to measure effective refractory periods (ERPs) and pacing thresholds, in order to assess excitability, electrical restitution kinetics, and susceptibility to stimulation-evoked tachyarrhythmias at epicardial and endocardial stimulation sites. In both ventricular chambers, Na(v) protein expression was higher at endocardium than epicardium, with midmyocardial layers showing intermediate expression levels. Endocardial stimulation sites showed higher excitability, as evidenced by lower pacing thresholds during regular stimulation and downward displacement of the strength-interval curve reconstructed after extrasystolic stimulation compared with epicardium. ERP restitution assessed over a wide range of pacing rates showed greater maximal slope and faster kinetics at endocardial than epicardial stimulation sites. Flecainide, a Na(+) channel blocker, reduced the maximal ERP restitution slope, slowed restitution kinetics, and eliminated epicardial-to-endocardial difference in dynamics of electrical restitution. Greater excitability and steeper electrical restitution have been associated with greater arrhythmic susceptibility of endocardium than epicardium, as assessed by measuring ventricular fibrillation threshold, inducibility of tachyarrhythmias by rapid cardiac pacing, and the magnitude of stimulation-evoked repolarization alternans. In conclusion, higher Na(+) channel expression levels may contribute to greater excitability, steeper electrical restitution slopes and faster restitution kinetics, and greater susceptibility to stimulation-evoked tachyarrhythmias at endocardium than epicardium in the guinea pig heart.