Lichy Han

Predictive Value of Beat-to-Beat QT Variability Index Across the Continuum of Left Ventricular Dysfunction Competing Risks of Noncardiac or Cardiovascular Death and Sudden or Nonsudden Cardiac Death

Background— The goal of the present study was to determine the predictive value of beat-to-beat QT variability in heart failure patients across the continuum of left ventricular dysfunction. Methods and Results— Beat-to-beat QT variability index (QTVI), log-transformed heart rate variance, normalized QT variance, and coherence between heart rate variability and QT variability have been measured at rest during sinus rhythm in 533 participants of the Muerte Subita en Insuficiencia Cardiaca heart failure study (mean age, 63.1±11.7; men, 70.6%; left ventricular ejection fraction >35% in 254 [48%]) and in 181 healthy participants from the Intercity Digital Electrocardiogram Alliance database. During a median of 3.7 years of follow-up, 116 patients died, 52 from sudden cardiac death (SCD). In multivariate competing risk analyses, the highest QTVI quartile was associated with cardiovascular death (subhazard ratio, 1.67 [95% CI, 1.14–2.47]; P=0.009) and, in particular, with non-SCD (subhazard ratio, 2.91 [1.69–5.01]; P<0.001). Elevated QTVI separated 97.5% of healthy individuals from subjects at risk for cardiovascular (subhazard ratio, 1.57 [1.04–2.35]; P=0.031) and non-SCD in multivariate competing risk model (subhazard ratio, 2.58 [1.13–3.78]; P=0.001). No interaction between QTVI and left ventricular ejection fraction was found. QTVI predicted neither noncardiac death (P=0.546) nor SCD (P=0.945). Decreased heart rate variability rather than increased QT variability was the reason for increased QTVI in the present study. Conclusions— Increased QTVI because of depressed heart rate variability predicts cardiovascular mortality and non-SCD but neither SCD nor extracardiac mortality in heart failure across the continuum of left ventricular dysfunction. Abnormally augmented QTVI separates 97.5% of healthy individuals from heart failure patients at risk.

Comparison of Sum Absolute QRST Integral, and Temporal Variability in Depolarization and Repolarization, Measured by Dynamic Vectorcardiography Approach, in Healthy Men and Women

Background Recently we showed the predictive value of sum absolute QRST integral (SAI QRST) and repolarization lability for risk stratification of sudden cardiac death (SCD) in heart failure patients. The goal of this study was to compare SAI QRST and metrics of depolarization and repolarization variability in healthy men and women. Methods Orthogonal ECGs were recorded at rest for 10 minutes in 160 healthy men and women (mean age 39.6±14.6, 80 men). Mean spatial TT′ angle, and normalized variances of T loop area, of spatial T vector amplitude, of QT interval and Tpeak-Tend area were measured for assessment of repolarization lability. Normalized variances of spatial QRS vector and QRS loop area characterized variability of depolarization. In addition, variability indices (VI) were calculated to adjust for normalized heart rate variance. SAI QRST was measured as the averaged arithmetic sum of areas under the QRST curve. Results Men were characterized by shorter QTc (430.3±21.7 vs. 444.7±22.2 ms; P<0.0001) and larger SAI QRST (282.1±66.7 vs.204.9±58.5 mV*ms; P<0.0001). Repolarization lability negatively correlated with spatial T vector amplitude. Adjusted by normalized heart rate variance, QT variability index was significantly higher in women than in men (−1.54±0.38 vs. −1.70±0.33; P = 0.017). However, in multivariate logistic regression after adjustment for body surface area, QTc, and spatial T vector amplitude, healthy men had 1.5–3 fold higher probability of having larger repolarization lability, as compared to healthy women (T vector amplitude variability index odds ratio 3.88(95%CI 1.4–11.1; P = 0.012). Conclusions Healthy men more likely than women have larger repolarization lability.

Beat-to-beat three-dimensional ECG variability predicts ventricular arrhythmia in ICD recipients

BACKGROUND Methodological difficulties associated with QT measurements prompt the search for new electrocardiographic markers of repolarization heterogeneity. OBJECTIVE We hypothesized that beat-to-beat 3-dimensional vectorcardiogram variability predicts ventricular arrhythmia (VA) in patients with structural heart disease, left ventricular systolic dysfunction, and implanted implantable cardioverter-defibrillators (ICDs). METHODS Baseline orthogonal electrocardiograms were recorded in 414 patients with structural heart disease (mean age 59.4 ± 12.0; 280 white [68%] and 134 black [32%]) at rest before implantation of ICD for primary prevention of sudden cardiac death. R and T peaks of 30 consecutive sinus beats were plotted in 3 dimensions to form an R peaks cloud and a T peaks cloud. The volume of the peaks cloud was calculated as the volume within the convex hull. Patients were followed up for at least 6 months; sustained VA with appropriate ICD therapies served as an end point. RESULTS During a mean follow-up time of 18.4 ± 12.5 months, 61 of the 414 patients (14.73% or 9.6% per person-year of follow-up) experienced sustained VA with appropriate ICD therapies: 41 of them were white and 20 were black. In the multivariate Cox model that included inducibility of VA and use of beta-blockers, the highest tertile of T/R peaks cloud volume ratio significantly predicted VA (hazard ratio 1.68, 95% confidence interval 1.01 to 2.80; P = .046) in all patients. T peaks cloud volume and T/R peaks cloud volume ratio were significantly smaller in black subjects (median 0.09 [interquartile range 0.04 to 0.15] vs. median 0.11 [interquartile range 0.06 to 0.22], P = .002). CONCLUSION A relatively large T peaks cloud volume is associated with increased risk of VA in patients with structural heart disease and systolic dysfunction.

Antiarrhythmic Effect of Reverse Electrical Remodeling Associated with Cardiac Resynchronization Therapy

Background: Antiarrhythmic and proarrhythmic effects of cardiac resynchronization therapy (CRT) remain controversial. We hypothesized that reverse electrical remodeling (RER) with CRT is associated with reduced frequency of ventricular tachyarrhythmias (VTs).

ECG marker of adverse electrical remodeling post-myocardial infarction predicts outcomes in MADIT II study

Background Post-myocardial infarction (MI) structural remodeling is characterized by left ventricular dilatation, fibrosis, and hypertrophy of the non-infarcted myocardium. Objective The goal of our study was to quantify post-MI electrical remodeling by measuring the sum absolute QRST integral (SAI QRST). We hypothesized that adverse electrical remodeling predicts outcomes in MADIT II study participants. Methods Baseline orthogonal ECGs of 750 MADIT II study participants (448 [59.7%] ICD arm) were analyzed. SAI QRST was measured as the arithmetic sum of absolute QRST integrals over all three orthogonal ECG leads. The primary endpoint was defined as sudden cardiac death (SCD) or sustained ventricular tachycardia (VT)/ventricular fibrillation (VF) with appropriate ICD therapies. All-cause mortality served as a secondary endpoint. Results Adverse electrical remodeling in post-MI patients was characterized by wide QRS, increased magnitudes of spatial QRS and T vectors, J-point deviation, and QTc prolongation. In multivariable Cox regression analysis after adjustment for age, QRS duration, atrial fibrillation, New York Heart Association heart failure class and blood urea nitrogen, SAI QRST predicted SCD/VT/VF (HR 1.33 per 100 mV*ms (95%CI 1.11–1.59); P = 0.002), and all-cause death (HR 1.27 per 100 mV*ms (95%CI 1.03–1.55), P = 0.022) in both arms. No interaction with therapy arm and bundle branch block (BBB) status was found. Conclusions In MADIT II patients, increased SAI QRST is associated with increased risk of sustained VT/VF with appropriate ICD therapies and all-cause death in both ICD and in conventional medical therapy arms, and in patients with and without BBB. Further studies of SAI QRST are warranted.

Intracardiac J-point elevation before the onset of polymorphic ventricular tachycardia and ventricular fibrillation in patients with an implantable cardioverter-defibrillator.

BACKGROUND The clinical importance of the J-point elevation on electrocardiogram is controversial. OBJECTIVE To study intracardiac J-point amplitude before ventricular arrhythmia. METHODS Baseline 12-lead electrocardiogram and far-field right ventricular intracardiac implantable cardioverter-defibrillator electrograms were recorded at rest in 494 patients (mean age 60.4 ± 13.1 years; 360 [72.9%] men) with structural heart disease (278 [56.3%] ischemic cardiomyopathy) who received primary (463 [93.9%] patients) or secondary prevention implantable cardioverter-defibrillator. Ten-second intracardiac far-field electrograms before the onset of arrhythmia were compared with the baseline. The J-point amplitude was measured on the baseline 12-lead surface electrocardiogram and the intracardiac far-field electrogram. The relative J-point amplitude was calculated as the ratio of J-point amplitude to peak-to-peak R-wave. RESULTS The paired t test showed that the relative intracardiac J-point amplitude was significantly higher before polymorphic ventricular tachycardia/ventricular fibrillation (VF) onset (0.28 ± 0.08 vs -0.19 ± 0.39; P = .012) than at baseline. In a mixed-effects logistic regression model, adjusted for multiple episodes per patient, each 10% increase in relative J-point amplitude increased the odds of having ventricular tachycardia/VF by 13% (odds ratio 1.13 [95% confidence interval 1.07-1.19]; P < .0001) and increased the odds of having polymorphic ventricular tachycardia/VF by 27% (odds ratio 1.27 [95% confidence interval 1.11-1.46]; P = .001). CONCLUSIONS The relative intracardiac J-point amplitude is augmented immediately before the onset of polymorphic ventricular tachycardia/VF in patients with structural heart disease.

Lability of R- and T-wave peaks in three-dimensional electrocardiograms in implantable cardioverter defibrillator patients with ventricular tachyarrhythmia during follow-up

INTRODUCTION From experiments, we know that the heterogeneity of action potential duration and morphology is an important mechanism of ventricular tachyarrhythmia. Electrocardiogram (ECG) markers of repolarization lability are known; however, lability of depolarization has not been systematically studied. We propose a novel method for the assessment of variability of both depolarization and repolarization phases of the cardiac cycle. METHODS Baseline orthogonal ECGs of 81 patients (mean ± SD age, 56 ± 13 years; 61 male [75%]) with structural heart disease and implanted single-chamber implantable cardioverter defibrillator (ICD) were analyzed. Clean 30-beat intervals with absence of premature beats were then selected. Baseline wandering was corrected before analysis. Peaks of R wave and peaks of T wave were detected for each beat, and the axis magnitude was calculated. The peaks were plotted to show clouds of peaks and then used to construct a convex hull, and the volumes of the R peaks cloud and T peaks cloud and ratio of volumes were calculated. RESULTS During a mean (SD) follow-up period of 13 (10) months, 9 of the 81 patients had sustained ventricular tachycardia or ventricular fibrillation (VT/VF) and received appropriate ICD therapies. All ICD events were adjudicated by three independent electrophysiologists. There was no statistically significant difference in the volume of T-wave peaks or R-wave peaks between patients with and without VT or VF during follow-up; however, R/T peaks cloud volume ratio was significantly lower in patients with subsequent VT/VF (22.4 ± 25.4 versus 13.1 ± 7.9, P = .024). CONCLUSIONS Larger volume of T peaks cloud, measured during 30 beats of three-dimensional ECG, is associated with higher risk of sustained ventricular tachyarrhythmias and appropriate ICD therapies. New method to assess temporal variability of repolarization in three-dimensional ECGs by measuring volume of peak clouds shows potential for further exploration for VT/VF risk stratification.

Beat‐to‐Beat Spatiotemporal Variability in the T Vector Is Associated With Sudden Cardiac Death in Participants Without Left Ventricular Hypertrophy: The Atherosclerosis Risk in Communities (ARIC) Study

Background Despite advances in prevention and treatment of cardiovascular disease, sudden cardiac death (SCD) remains a clinical challenge. Risk stratification in the general population is needed. Methods and Results Beat‐to‐beat spatiotemporal variability in the T vector was measured as the mean angle between consecutive T‐wave vectors (mean TT′ angle) on standard 12‐lead ECGs in 14 024 participants in the Atherosclerosis Risk in Communities (ARIC) study. Subjects with left ventricular hypertrophy, atrial arrhythmias, frequent ectopy, ventricular pacing, or QRS duration ≥120 ms were excluded. The mean spatial TT′ angle was 5.21±3.55°. During a median of 14 years of follow‐up, 235 SCDs occurred (1.24 per 1000 person‐years). After adjustment for demographics, coronary heart disease risk factors, and known ECG markers for SCD, mean TT′ angle was independently associated with SCD (hazard ratio 1.089; 95% CI 1.044 to 1.137; P<0.0001). A mean TT′ angle >90th percentile (>9.57°) was associated with a 2‐fold increase in the hazard for SCD (hazard ratio 2.01; 95% CI 1.28 to 3.16; P=0.002). In a subgroup of patients with T‐vector amplitude ≥0.2 mV, the association with SCD was almost twice as strong (hazard ratio 3.92; 95% CI 1.91 to 8.05; P<0.0001). A significant interaction between mean TT′ angle and age was found: TT′ angle was associated with SCD in participants aged <55 years (hazard ratio 1.096; 95% CI 0.043 to 1.152; P<0.0001) but not in participants aged ≥55 years (Pinteraction=0.009). Conclusions In a large, prospective, community‐based cohort of left ventricular hypertrophy–free participants, increased beat‐to‐beat spatiotemporal variability in the T vector, as assessed by increasing TT′ angle, was associated with SCD.

Mechanical alternans is associated with mortality in acute hospitalized heart failure prospective mechanical alternans study (mas)

Background—Acute hospitalized heart failure (AHHF) is associated with 40% to 50% risk of death or rehospitalization within 6 months after discharge. Timely (before hospital discharge) risk stratification of patients with AHHF is crucial. We hypothesized that mechanical alternans (MA) and T-wave alternans (TWA) are associated with postdischarge outcomes in patients with AHHF. Methods and Results—A prospective cohort study was conducted in the intensive cardiac care unit and enrolled 133 patients (59.6±15.7 years; 65% men) admitted with AHHF. Surface ECG and peripheral arterial blood pressure waveform via arterial line were recorded continuously during the intensive cardiac care unit stay. MA and TWA were measured by enhanced modified moving average method. All-cause death or heart transplant served as a combined primary end point. MA was observed in 28 patients (25%), whereas TWA was detected in 33 patients (33%). If present, MA was tightly coupled with TWA. Mean TWA amplitude was larger in patients with both TWA and MA when compared with patients with lone TWA (median, 37 [interquartile range, 26–61] versus 22 [21–23] &mgr;V; P=0.045). After a median of 10-month postdischarge, 42 (38%) patients died and 2 had heart transplants. MA was associated with the primary end point in univariable Cox model (hazard ratio, 1.84; 95% confidence interval, 1.00–3.40; P=0.05) and after adjustment for left ventricular ejection fraction, New York Heart Association HF class, and implanted implantable cardioverter defibrillator/cardiac resynchronization therapy defibrillator (hazard ratio, 2.12 95% confidence interval, 1.13–3.98; P=0.020). TWA without consideration of simultaneous MA was not significantly associated with primary end point (hazard ratio, 1.42; 95% confidence interval, 0.77–2.64; P=0.260). Conclusions—MA is independently associated with outcomes in AHHF. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01557465.

Complex assessment of the temporal lability of repolarization

Stochastic fluctuations of IKs in the presence of cell-to-cell uncoupling leads to temporal variability of action potential duration and subsequent early afterdepolarizations, which occur in late phase 2 or phase 3 of the cardiac action potential, could propagate through cardiac tissue and generate ventricular arrhythmias (1;2). However, surface ECG imposes well-recognized limitations for repolarization assessment: dependence on particular ECG lead axis and inaccuracies in the T end detection. In contrast, vectorcardiograms (VCGs) have advantages in their description of repolarization(3). Recently we proposed a novel 3-dimensional (3-D) ECG method to assess temporal repolarization lability(4;5). However, the complexity of spatial T-vector movements over time makes it unlikely that any single method would describe temporal lability of repolarization in full. Therefore, the goal of this study was to develop a comprehensive set of markers of temporal lability of repolarization in a discriminating model.