Risk Stratification Using Novel Approaches for
Analyzing Ventricular Arrhythmias

Ryszard Piotrowicz

National Institute of Cardiology, Department of Cardiac Rehabilitation and Noninvasive Electrocardiology,
Warsaw, Poland

Correspondence: Ryszard Piotrowicz, National Institute of Cardiology.
E-mail: rpiotrowicz@aorta.ikard.waw.pl, phone 48 22 815 28 47, fax 48 22 815 28 47

1.  Introduction

Due to the multifactorial pathogenesis of sudden cardiac death, risk stratification using only a single parameter is highly unlikely to provide the clinician with the information needed to decide whether a patient should receive primary preventive therapy to alleviate malignant ventricular arrhythmias. The bulk of evidence indicates that a combination of risk markers must be applied. Risk stratification strategy should include at least one parameter of left ventricular contractile function such as determination of LVEF, one reflecting ischemia, one reflecting cardiac autonomic tone (HRV and/or BRS), one reflecting electrical instability (ventricular arrhythmias), and one evaluating inhomogeneity of ventricular repolarization. Data obtained in the general population of postinfarction patients in the thrombolytic era indicate that the presence of ventricular premature beats and even nonsustained ventricular tachycardia early after infarction in patients treated following modern therapeutic guidelines does not appear to be a powerful prognostic marker. Also, the analysis of simple QT dispersion calculated in sinus beats may not yield prognostic information, mainly due to its technological pitfalls. The aim of this paper is to discuss new parameters reflecting repolarization abnormalities of spontaneous and paced ventricular premature beats and parameters describing heart rate variability of ventricular tachycardia.

2.  Dispersion of QT Interval in Ventricular Beats

Because of anisotropic conduction and prematurity of activation the electrophysiological properties of ventricular myocardium may be altered by ventricular premature beats, which are well-established triggers for sustained VT. In 1992, Day et al. reported that shifting activation from simultaneous biventricular to sequential activation during right ventricular stimulation alters the pattern of repolarization and hence changes the duration of QT dispersion measured in paced ventricular beats in the normal heart (2). Also it has been shown that ventricular beats (VPB) further increase inhomogeneity of ventricular repolarization and may facilitate initiation of reentrant ventricular arrhythmia (15,16). Dispersion of repolarization calculated in VPBs (QTdV) is a novel approach to assess inhomogeneity of ventricular recover time. In 1998, we published the first study focusing on methodical problems and clinical significance of QTdV (7). We were able to demonstrate that the QTdV values obtained from simultaneous 12-lead ECG were remarkably similar to those calculated from six limbs and six precordial leads. The use of six limbs and six pericardial leads provide reliable information similar to that obtained by the analysis of simultaneous 12 leads. We also found that patients with cardiac disease had significantly higher values of QTdV than it was observed in apparently healthy subjects, and also that patients with ventricular tachycardia had higher QTdV than patients without such arrhythmia. This preliminary work let us to conclude that measurement of QTdV, defined as the difference between the longest and the shortest QT intervals measured in VPBs, might be a useful noninvasive method for detecting the inhomogeneity of ventricular recovery time.

Subsequently, we studied the prognostic value of QTdV in 193 postinfarction patients (8). During a mean follow-up of 38±17 months, there were 56 deaths (29%). Univariate predictors of mortality included QTdV ³ 100 ms, JT dispersion ³100 ms, EF < 40%, complete bundle branch block, R-on-T index of ventricular premature beats < 1, and age of patients > 60 years. In multivariate Cox proportional hazards survival analysis, only QTdV ³ 100 ms, EF <40%, and complete bundle branch block were independent and significant predictors of mortality. The final model selected increased QTdV as the prognostic factor, which was the most strongly associated with mortality.

In 2000, we assessed the relation between QTdV and QTd in sinus beats (QTd-S) and compared the prognostic significance of these two variables in 148 postinfarction patients (9). In the total group of patients, QTdV was greater than QTd-S (83±33 versus 74±34 ms, respectively; p=0.001). During a mean follow-up period of 35±17 months, arrhythmic events (sustained ventricular tachycardia, ventricular fibrillation, or sudden death) were observed in 30 patients (20%). A QTd-V of ³100 ms was a stronger univariate marker of arrhythmic events than was QTd-S of ³ 100 ms, and multivariate analysis selected only prolonged QTd-V (hazard ratio 3.81,95% CI 2.2 to 11.2) and low ejection fraction (hazard ratio 3.05,95% CI 1.6 to 7.6) as independent predictors of arrhythmic events. We concluded that prolonged QTd-V is associated with a significantly increased risk for arrhythmic events in postinfarction patients, and prognostic significance of QTd-V exceeds that of QTd-S.

In 2001 Kułakowski et al. analyzed the value of QT dispersion in sinus beats and ventricular premature beats for identification of patients with inducible sustained VT during electrophysiological study (14). The authors hypothesized that QTd in spontaneous or paced ventricular beats may improve identification of patients with inducible sustained VT. In 28 consecutive patients (mean age 61±14 years) who underwent programmed ventricular stimulation, the values of QTd calculated in sinus and ventricular beats were compared between inducible and noninducible patients. The mean QTd values obtained using three different methods differed significantly, QTd in paced ventricular beats being the highest, QTd in spontaneous ventricular beats was intermediate, and QTd in sinus beats was the lowest (83,9±30 vs. 63±29 ms vs. 53.9 ± 27, p< 0.0001 and p<0.004, respectively). In 13 patients (46%), sustained VT was induced. QTd values were significantly higher in inducible than noninducible patients (QTd sinus beats: 67.5±31 vs. 42.1 ± 11 ms, p=0.02; QTd spontaneous ventricular beats 79.3 ±35 vs. 46.7 ±13 ms, p=0.008, and QTd- paced ventricular beats: 104,8±32 vs. 65.9±9ms, p=0.0009). The receiver operator characteristic curves showed that at a sensitivity level of 100%, the highest specificity for identification of inducible patients had QTd measured in paced ventricular beats (87%) followed by QTd in spontaneous ventricular beats (45%) and QTd in sinus beats (40%). The authors concluded that QTd in ventricular beats is greater than in sinus beats and that QTd calculated from paced ventricular beats identifies patients with inducible sustained VT better than QTd measured during sinus rhythm.

The data presented above demonstrate that QTd in spontaneous ventricular beats and in paced ventricular beats is greater than QTd in sinus beats. QTd in ventricular beats is a new parameter reflecting repolarization abnormalities and is associated with a significantly increased risk for arrhythmic events. Measurement of QTd in ventricular beats may improve the effectiveness of risk stratification after myocardial.

3.  QT Interval in Premature Ventricular Beats

In 1991 Dąbrowski et al. evaluated the response of the QT interval to ventricular pacing in patients with induced VT and in patients without such arrhythmia (3). They demonstrated that ventricular stimulation shortens QT interval in both groups. However, in subjects without inducible VT this shortening of QT interval was significantly greater. Thus, a trend toward longer QT values of ventricular paced rhythm exists in patients with inducible VT. In 2001, Dąbrowski et al. published the first and only study evaluating the prognostic significance of QT interval measured in spontaneous premature ventricular beats (10). In 168 postinfarction patients with VPBs on a standard ECG the values of: QT in VPB (QT-V), corrected for heart rate QT-V (QTc-V), absolute and corrected JT interval of premature ventricular beats (JT-V and JTc-V), QRS complex of VPBs (QRS-V) and R-R interval of basic heart rhythm were calculated. During follow-up period of 38 ± 17 months the arrhythmic event (sudden cardiac death, sustained VT or VF) occurred in 34 patients. Among the evaluated variables QTc-V > 540 ms was the strongest marker of arrhythmic events in univariate analysis. Multivariate analysis revealed the independent predictive value of QTc-V > 540 ms (hazard ratio 3.38; p=0.0012) and EF < 40% (hazard ratio 2.78; p=0.053). Authors concluded that the measurement of QTc-V might also be used for risk stratification in patients after myocardial infarction.

4.  Ventricular Tachycardia Rate Variability in Nonsustained Ventricular Tachycardia

Clinical and experimental observations indicate that reduced beat-to-beat changes in the cycle length of nonsustained ventricular tachycardia (NSVT) may indicate the risk of malignant VT and sudden cardiac death (1,11 - 13). In context of the abovementioned data we assessed ventricular rate variability during NSVT (4). We described the characteristics of ventricular rate variability (VRV) in patients with NSVT and tested the hypothesis that the measurement of VRV-NSVT may be useful in identifying patients at high risk of life-threatening arrhythmic events. In 326 patients who had NSVT on 24-hour ECG, temporal changes in up to 10 beat-to-beat intervals of NSVT runs (V-V) were assessed. The following parameters of VRV-NSVT were calculated: average value of successive differences in V-V intervals (ADVV) and normalized average value of successive differences in V-V intervals (nADVV). During a mean follow-up of 4 years, 52 (16%) patients had a documented episode of sustained VT or VF. Patients with these arrhythmic events had significantly (p< 0.001) lower values of ADVV and nADVV variables in comparison to patients without arrhythmic events. The relative risk of malignant arrhythmic events for patients with ADVV< 40 ms was 4.9 (p<0.001), for patients with nADVV < 6% the risk was 3.9 (p=0.001). The results of this study indicate a strong and significant relationship between NSVT and the risk of subsequent malignant VT. We concluded that the assessment of VRV-NSVT may be useful for identifying patients at high and low risk for subsequent arrhythmic events. In the next paper, we observed 162 patients with remote myocardial infarction who showed NSVT on 24-hour ECG (5). During a mean follow-up of 4 years, 57 patients (35%) had died. Sudden death was identified in 34 patients (21%). They had significantly (p<0.001) lower values of ADVV and nADVV variables compared with survivors or those whose death was not sudden. The relative risk of sudden death for patients with ADVV values < 30 ms was 3.2 compared with those with ADVV ³ 30 ms (p=0.001), and that for patients with ADVV < 6% was 3.0 compared with those with nADVV ³6% (p<0.001). These results indicate a relationship between regularity of NSVT rhythm and risk of sudden death.

The purpose of the next study was: (1) to evaluate the predictive value of VRV-NSVT used alone and in conjunction with other risk predictors, and (2) to determine whether assessment of VRV adds independent prognostic information to clinical descriptors, other ambulatory electrocardiographic monitoring features, and left ventricular EF (6). The study group consisted of 191 postinfarction patients. The mean age was 59±10 years. During a follow-up of 34 ±2 months, 71 patients (37%) died; sudden death was identified in 45 patients (24%). In patients who died suddenly, VRV was significantly reduced compared with those without sudden death (32.1±5.3 vs. 65.7±5.4 ms, p<0.001). Multivariate analysis of survival using the Cox proportional-hazards model showed two descriptors to be independent predictors of sudden cardiac death: VRV-NSVT < 30 ms and left ventricular EF. Using a stepwise approach, VRV power had the strongest association with sudden cardiac death (chi-square 17.6765,p<0.001). The combination of VRV< 30 ms and left ventricular EF < 40% improved the prediction of sudden deaths (chi-square 25.5310, p<0.001).

5.  Conclusions

Novel approaches for analyzing ventricular arrhythmias seems to be promising methods contributing to a multiparameter algorithm for risk stratification in patients after myocardial infarction

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