Larisa G. Tereshchenko

Prediction of Ventricular Tachyarrhythmias by Intracardiac Repolarization Variability Analysis

Background—Arrhythmic sudden cardiac death (SCD) is generally mediated by ventricular fibrillation (VF) or fast ventricular tachycardia (FVT). We studied the predictive value of temporal QT variability detected from various sources of cardiac electric signal: surface ECG, far-field (FF), and near-field (NF) intracardiac electrograms (EGMs) in patients with implantable cardioverter-defibrillators (ICDs). Methods and Results—Surface ECG and FF and NF intracardiac EGMs were simultaneously recorded at rest (mean heart rate, 74±15 bpm) for 4.5±1.3 minutes in 298 patients (mean age, 59±14; 216 male [73%]) with structural heart disease and an implanted Medtronic ICD for primary (231 patients, 78%) or secondary (67 patients, 22%) prevention of SCD. During mean follow-up of 16±8 months, 52 (13.1% per person-year of follow-up) patients sustained VT/VF and received appropriate ICD therapies, but only 19 (4.8% per person-year of follow-up) patients sustained FVT/VF with cycle length ≤240 ms. The Kaplan–Meier survival analysis showed that the highest QT variability index (QTVI) quartile from all cardiac sources (surface ECG; NF and FF EGMs) is associated with event-free survival (P=0.038 for ECG; P=0.024 for FF EGM; P=0.012 for NF EGM). QTVI was a predictor of all VT/VF events and FVT/VF in the multivariate Cox model (including ischemic or nonischemic cardiomyopathy, history of revascularization procedures, LVEF, New York Heart Association class). Strong significant correlation among QTVI determined from all 3 sources was found. Conclusion—Repolarization lability is present throughout the ventricular myocardium. Increased intracardiac QT variability predicts VT/VF events in patients with structural heart disease.

Transient Local Injury Current in Right Ventricular Electrogram After Implantable Cardioverter-Defibrillator Shock Predicts Heart Failure Progression

OBJECTIVESnThis study aimed to identify an early marker of functional impairment after an implantable cardioverter-defibrillator (ICD) shock as a predictor of heart failure progression.nnnBACKGROUNDnThe ICD population has substantial risk of death due to progressive pump failure.nnnMETHODSnNear-field (NF) bipolar right ventricular (RV) electrograms (EGMs) during induced ventricular fibrillation (VF) and 10 s after rescue ICD shock were analyzed in 310 patients (mean age 59 +/- 14.5 years, 219 men [71%]) with structural heart disease, New York Heart Association functional class I to III, and implanted with a single- or dual-chamber Medtronic (Minneapolis, Minnesota) ICD for primary (245 patients, 79%) or secondary prevention of sudden cardiac arrest. A local injury current (LIC) on NF RV EGM was defined as a deviation of EGM potential > or =1 mV or > or =15% of the preceding R-wave peak-to-peak amplitude.nnnRESULTSnDuring mean follow-up of 29.3 +/- 15.0 months, the combined end point of death or hospitalization due to congestive heart failure (CHF) exacerbation was documented in 40 patients (12.9%, or 5.3% per person-year of follow-up). LIC was observed in 106 patients. In multivariate risk analysis, after adjustment for baseline prognostic factors (ejection fraction, history of atrial fibrillation, diabetes mellitus) and appropriate ICD shocks during follow-up, patients with observed LIC after induced VF rescue ICD shock at ICD implantation were more likely to die or to be hospitalized (hazard ratio: 2.69; 95% confidence interval: 1.41 to 5.14; p = 0.003).nnnCONCLUSIONSnTransient LIC on bipolar NF RV EGM after induced VF rescue ICD shock is associated with increased risk of CHF progression, future hospitalizations due to CHF exacerbation, and subsequent heart failure death.

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; Pu200a=u200a0.017). 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; Pu200a=u200a0.012). Conclusions Healthy men more likely than women have larger repolarization lability.

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

BACKGROUNDnMethodological difficulties associated with QT measurements prompt the search for new electrocardiographic markers of repolarization heterogeneity.nnnOBJECTIVEnWe 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).nnnMETHODSnBaseline 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.nnnRESULTSnDuring 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).nnnCONCLUSIONnA relatively large T peaks cloud volume is associated with increased risk of VA in patients with structural heart disease and systolic dysfunction.

A new electrocardiogram marker to identify patients at low risk for ventricular tachyarrhythmias: sum magnitude of the absolute QRST integral

OBJECTIVEnWe proposed and tested a novel electrocardiogram marker of risk of ventricular arrhythmias (VAs).nnnMETHODSnDigital orthogonal electrocardiograms were recorded at rest before implantable cardioverter-defibrillator (ICD) implantation in 508 participants of a primary prevention ICDs prospective cohort study (mean ± SD age, 60 ± 12 years; 377 male [74%]). The sum magnitude of the absolute QRST integral in 3 orthogonal leads (SAI QRST) was calculated. A derivation cohort of 128 patients was used to define a cutoff; a validation cohort (n = 380) was used to test a predictive value.nnnRESULTSnDuring a mean follow-up of 18 months, 58 patients received appropriate ICD therapies. The SAI QRST was lower in patients with VA (105.2 ± 60.1 vs 138.4 ± 85.7 mV ms, P = .002). In the Cox proportional hazards analysis, patients with SAI QRST not exceeding 145 mV ms had about 4-fold higher risk of VA (hazard ratio, 3.6; 95% confidence interval, 1.96-6.71; P < .0001) and a 6-fold higher risk of monomorphic ventricular tachycardia (hazard ratio, 6.58; 95% confidence interval, 1.46-29.69; P = .014), whereas prediction of polymorphic ventricular tachycardia or ventricular fibrillation did not reach statistical significance.nnnCONCLUSIONnHigh SAI QRST is associated with low risk of sustained VA in patients with structural heart disease.

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).

Ventricular arrhythmia is predicted by sum absolute QRST integralbut not by QRS width

BACKGROUNDnThere is a controversy regarding the association between QRS width and ventricular arrhythmias (VAs). We hypothesized that predictive value of the QRS width could be improved if QRS width were considered in the context of the sum magnitude of the absolute QRST integral in 3 orthogonal leads sum absolute QRST integral (SAI QRST). We explored correlations between QRS width, SAI QRST, and VA in primary prevention implantable cardioverter-defibrillator (ICD) patients with structural heart disease.nnnMETHODSnBaseline orthogonal electrocardiograms were recorded at rest in 355 patients with implanted primary prevention ICDs (mean age, 59.5 ± 12.4 years; 279 male [79%]). Patients were observed prospectively at least 6 months; appropriate ICD therapies because of sustained VA served as end points. The sum magnitude of the absolute QRST integral in 3 orthogonal leads (SAI QRST) was calculated.nnnRESULTSnDuring a mean follow-up of 18 months, 48 patients had sustained VA and received appropriate ICD therapies. There was no difference in baseline QRS width between patients with and those without arrhythmia (114.9 ± 32.8 vs 108.9 ± 24.7 milliseconds; P = .230). SAI QRST was significantly lower in patients with VA at follow-up than in patients without VA (102.6 ± 27.6 vs 112.0 ± 31.9 mV·ms; P = 0.034). Patients with SAI QRST (≤145 mV·ms) had a 3-fold higher risk of ventricular tachycardia (VT)/ventricular fibrillation (VF) (hazard ratio [HR], 3.25; 95% confidence interval [CI], 1.59-6.75; P = .001). In the univariate analysis, QRS width did not predict VT/VF. In the bivariate Cox regression model, every 1 millisecond of incremental QRS widening with a simultaneous 1 mV·ms SAI QRST decrease raised the risk of VT/VF by 2% (HR, 1.02; 95% CI, 1.01-1.03; P = .005).nnnCONCLUSIONnQRS widening is associated with ventricular tachyarrhythmia only if accompanied by low SAI QRST.

Intracardiac QT variability in patients with structural heart disease on class III antiarrhythmic drugs

We previously showed that increased intracardiac repolarization lability predicts life-threatening ventricular arrhythmias in patients with structural heart disease. Patients with structural heart disease frequently take antiarrhythmic drugs (AADs), which directly affect repolarization. The effect of AADs on the predictive value of repolarization lability is unknown. We hypothesized that increased intracardiac beat-to-beat QT variability predicts sustained ventricular tachyarrhythmias in structural heart disease patients on class III AADs. Intracardiac electrograms and surface electrocardiogram were simultaneously recorded at rest for 5 minutes in 500 patients (mean +/- SD age, 61 +/- 14 years; 368 male [74%]) with implanted implantable cardioverter-defibrillator for primary (295 patients, or 79%) or secondary prevention of sudden cardiac death. Mean (SD) follow-up currently reached 24.8 (11.7) months. Intracardiac QT variability index was an independent predictor of ventricular tachycardia/ventricular fibrillation events and fast ventricular arrhythmias with cycle length of 240 ms or less in the multivariate Cox model. Intracardiac QT variability was higher in patients on class III AADs than in those not taking these drugs. Increased intracardiac QT variability after adjustment for class III AADs use carried independent risk of life-threatening ventricular tachyarrhythmias.

Screening entire health system ECG databases to identify patients at increased risk of death.

Background—Current methods to identify patients at higher risk for sudden cardiac death, primarily left ventricular ejection fraction ⩽35%, miss ≈80% of patients who die suddenly. We tested the hypothesis that patients with elevated QRS-scores (index of myocardial scar) and wide QRS-T angles (index abnormal depolarization–repolarization relationship) have high 1-year all-cause mortality and could be further risk stratified with clinical characteristics. Methods and Results—We screened all 12-lead ECGs over 6 months at 2 large hospital systems and analyzed clinical characteristics and 1-year mortality. Patients with ECGs obtained in hospital areas with known high mortality rates were excluded. At the first hospital, QRS-score ≥5 and QRS-T angle ≥105° identified 8.0% of patients and was associated with an odds ratio of 2.79 (95% confidence interval, 2.10–3.69) for 1-year mortality compared with patients below both ECG thresholds (13.9% versus 5.5% death rate). Left ventricular ejection fraction was >35% in 82% of the former group of patients, and addition of ECG measures to left ventricular ejection fraction increased the discrimination of death risk (P<0.0001). At the second hospital, the odds ratio was 2.42 (1.95–3.01) for 1-year mortality (8.8% versus 3.8%). Adjustment for patient characteristics eliminated interhospital differences. Multivariable adjusted odds ratio combining data from both hospitals was 1.53 (1.28–1.83). Increasing heart rate and chronic renal impairment further predicted mortality. Conclusions—Screening hospital ECG databases with QRS-scoring and QRS-T angle analysis identifies patients with high 1-year all-cause mortality and predominantly preserved left ventricular ejection fraction. This approach may represent a widely available method to identify patients at increased risk of death.