Nonsustained ventricular tachycardia: where do we stand?

Demosthenes G Katritsis* and A.John Camm

Department of Cardiology, Athens Euroclinic, 9 Athanassiadou Street, Athens 11521, Greece
Department of Cardiological Sciences, St. George's Hospital Medical School, London, UK

Received December 11, 2003; revised March 5, 2004; accepted March 18, 2004 * Corresponding author. Tel.: +30-210-641-6600; fax: +30-210-681-9779
E-mail address: dkatrits{at}otenet.gr


    Abstract
 Top
 Abstract
 Introduction
 Novel data on NSVT
 Clinical approach
 Conclusions
 References
 
The clinical approach to the patient with nonsustained ventricular tachycardia (NSVT) should always be considered within the particular clinical context in which the arrhythmia occurs. In the documented absence of heart disease, spontaneous NSVT does not carry any adverse prognostic significance. Exercise-induced NSVT may predict increased cardiac mortality. In ischaemic patients with a left ventricular ejection fraction (LVEF)40%, NSVT has an adverse prognostic significance and electrophysiologic testing is indicated with a view to ICD implantation. In patients with LVEF40% the independent prognostic significance of NSVT is unknown. The prognostic value of NSVT in patients with dilated cardiomyopathy is not known. NSVT in young patients with hypertrophic obstructive cardiomyopathy carries an adverse prognostic significance. The prognostic value of NSVT in conditions such as the long-QT syndromes, primary ventricular fibrillation, and Brugada syndrome, as well as in patients with hypertension and valvular disease, has not been established.

Key Words: Ventricular tachycardia • Nonsustained


    Introduction
 Top
 Abstract
 Introduction
 Novel data on NSVT
 Clinical approach
 Conclusions
 References
 
Nonsustained ventricular tachycardia (NSVT) is one of the most common problems encountered in modern clinical cardiology. The term, defined as 3 or more consecutive beats arising below the atrioventricular node with a rate 120 beats/min and lasting less than 30 s,1–3 denotes an electrocardiographic finding that can be associated with an extremely wide range of clinical conditions, from patients with significant heart disease and annual mortality rates exceeding 50% to asymptomatic, apparently healthy, young individuals. In several clinical settings NSVT is a marker of increased risk for subsequent sustained tachyarrhythmia and sudden cardiac death.3 However, even today it is not known whether NSVT has a cause-and-effect relationship with sustained ventricular tachyarrhythmias or is merely a surrogate marker of left ventricular dysfunction and electrical instability. Even in the case where it does hold prognostic significance, NSVT is not necessarily involved in the mechanism of death. There are certain patient groups with a high mortality due to progress of their disease. Death in these patients may be arrhythmic but this does not mean that merely preventing NSVT will unconditionally prolong life significantly. In several trials, reduction of arrhythmias or even arrhythmic death was not associated with a concomitant reduction in total mortality.4–6

The physician attending a patient presenting with an episode of NSVT has two tasks. First, to establish whether underlying occult pathology is responsible for the arrhythmia and, in the case of diagnosed heart disease, to risk-stratify the patient for appropriate management and therapy. The clinical approach to the patient with NSVT should always be considered within the particular clinical context in which the arrhythmia occurs. In several settings the patient with NSVT is a clinical challenge insofar as proper management is concerned, and several questions remain unanswered.


    Novel data on NSVT
 Top
 Abstract
 Introduction
 Novel data on NSVT
 Clinical approach
 Conclusions
 References
 
Reliable epidemiologic data on NSVT are difficult to obtain. Most of the available information comes from older studies based on Holter monitoring. Usually, although not invariably, patients remain asymptomatic; the reproducibility of NSVT recordings is documented in only half of the patients with this arrhythmia.7 The advent of implantable permanent pacemakers and implantable cardioverter defibrillators (ICD) with extensive ECG monitoring capabilities has made it possible to compile considerable information from patients with heart disease. There is emerging evidence from ICD data that NSVT is a distinct tachyarrhythmia that may cause syncope without causing death in patients with heart disease, and that the incidence of polymorphic NSVT relative to sustained arrhythmia is greater than previously believed.8 Reports from the Analysis of the Multicenter UnSustained Tachycardia Trial (MUSTT)9 substudies have provided valuable information regarding the prevalence and prognostic significance of NSVT in the context of different clinical settings. It seems that not only the frequency of NSVT but the circumstances under which it occurs are important. MUSTT data have shown prognostic differences in patients with in-hospital, as opposed to out-of-hospital, identified NSVT.10 Overall mortality rates at two and five years of follow-up were 24% and 48%, respectively, for inpatients and 18% and 38% for outpatients (adjusted ). In patients undergoing surgical coronary revascularisation, the occurrence of NSVT within the early (first 10 days) postrevascularisation period portends a far better outcome than when it occurs later after CABG (10–30 days) or in nonpostoperative settings.11 Indeed, the approximate 2-year mortality rates for patients with early postrevascularisation NSVT, late postrevascularisation NSVT, and nonpostoperative NSVT were 14%, 23%, and 24%, respectively.11 However, when sustained ventricular tachycardia is inducible in patients with early postoperative NSVT, the outcome is worse than in noninducible patients.12 In the MUSTT, racial differences have also been shown to influence the outcome of patients with NSVT and reduced left ventricular function.13


    Clinical approach
 Top
 Abstract
 Introduction
 Novel data on NSVT
 Clinical approach
 Conclusions
 References
 
Apparently healthy individuals
Initial reports indicated that the presence of complex ventricular ectopy and NSVT increase the risk of subsequently observed heart disease.14,15 However, when the presence of occult ischaemia or structural heart disease was excluded, NSVT was not found to adversely influence prognosis, with cardiac event rates not exceeding those detected in age-matched populations without the arrhythmia.16,17 Tachycardia originating from the right ventricular outflow tract (RVOT), one of the commonest causes of NSVT in apparently healthy individuals, may cause symptoms but the risk of death is very low.18,19 Thus, recording of spontaneous NSVT in apparently healthy individuals does not imply an adverse prognosis, provided that occult cardiomyopathy and genetic arrhythmia disorders are excluded. These conditions may remain latent for several years and although apparently healthy individuals presenting with NSVT can be reassured about their prognosis, long-term follow-up is advisable. There is continually accumulating evidence for occult pathology in apparently normal subjects who develop ventricular arrhythmia.20–22 Patients with RVOT ventricular tachycardia might have subtle structural and functional abnormalities of the outflow tract as detected by magnetic resonance imaging20 and the diagnosis of RVOT ventricular tachycardia needs to be differentiated from the diagnosis of arrhythmogenic right ventricular dysplasia23 and right ventricular myocarditis.

The occurrence of premature ventricular depolarisation during exercise in apparently healthy subjects has not been associated with an increase in cardiovascular mortality and was considered to be a normal response to exertion.24–27 It appears now that the long-term prognostic implications of exercise-induced ventricular arrhythmias may be adverse. Recently, the Paris Prospective Study28 has confirmed earlier data29 and reported that runs of two or more consecutive ventricular depolarisations during exercise or at recovery may occur in up to 3% of healthy men and indicate an increase in cardiovascular mortality within the next 23 years by a factor of more than 2.5. This increased relative risk persisted even after adjusting for other characteristics and known predisposition to coronary artery disease. Interestingly, among subjects with a positive exercise test for ischaemia, only 3% had ectopy, whereas among subjects with exercise-induced ectopy only 6% had a positive exercise test for ischaemia. Thus, although the precise mechanism of arrhythmia is unknown in this setting and various forms of occult cardiomyopathy cannot be excluded, it does not appear to be a direct consequence of ischaemia. This study argues that exercise-induced nonsustained ventricular arrhythmia may predict coronary artery disease even in the absence of evidence of ischaemia in asymptomatic individuals.

Exercise testing may also induce catecholaminergic polymorphic ventricular tachycardia.30,31 When recognised, this condition requires aggressive management.

Patients with heart disease
Ischaemic heart disease
The occurrence of NSVT during the first day of acute myocardial infarction, although frequent (40% to 70% of patients), is not associated with increased risk for subsequent long-term mortality.32 Following the first 24 h postinfarction, NSVT is detected in approximately 5–10% of the patients, particularly during the first months, and has been considered to have adverse prognostic significance.33–35

Previous studies have emphasised the importance of NSVT as an important prognostic determinant for arrhythmic death, even independent of left ventricular ejection fraction (LVEF).36,37 It now appears that in the patient with ischaemic heart disease, NSVT no longer appears to be an independent predictor of death if other factors such as the ejection fraction are taken into account. In the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-2 (GISSI-2, Italian Group for the Study of Survival after Myocardial Infarction-2) trial, NSVT was a significant predictor of mortality in univariate analysis, but not independently in multivariate analysis involving other clinical variables.35 Similarly, in the electrophysiologic study versus electrocardiographic monitoring (ESVEM) trial, although univariate analysis suggested that there was an association between the presenting arrhythmia and outcome, multivariate analysis failed to establish the predictive value of the presenting arrhythmia.38 Left ventricular ejection fraction was the single most important predictor of arrhythmic death or cardiac arrest in patients with life-threatening arrhythmias who were treated with antiarrhythmic drugs. Over a 6-year follow-up period, 285 of the 486 patients enrolled in the ESVEM trial had an arrhythmia recurrence. Patients with LVEF40% had a 5% risk of developing a malignant arrhythmia, whereas for each decrease of 5% in LVEF, the risk of cardiac arrest or arrhythmic death increased by 15%.38 In another study in which most patients (78%) had revascularisation of the infarct-related artery, NSVT early after myocardial infarction (4–16 days) had a low prevalence (9%) and carried a significant but low relative risk for the composite endpoint of cardiac death, ventricular tachycardia, or ventricular fibrillation, but not for arrhythmic events considered alone.39 Interestingly, in a recent analysis of 1071 ATRAMI patients, many of which underwent thrombolysis (63%), NSVT (with a prevalence of 13.4%) was found to adversely influence prognosis, independent of reduced LVEF.40

Although Holter monitoring is a valuable diagnostic tool in detecting patients with NSVT, its usefulness for the subsequent follow-up and evaluation of treatment is questionable. First, the prognostic significance of the frequency of NSVT runs or other ECG variables such as heart rate and complex ventricular ectopy is unknown. Recent trials in postinfarction patients have yielded conflicting evidence with regards to the relationship between the frequency of ventricular ectopy and heart rate with cardiac mortality.41,42 It seems that in the beta-blocking era, all common arrhythmia risk variables, including NSVT, have diminished predictive power in identifying postinfarction patients at risk of sudden cardiac death.43 Second, the suppression of frequent ventricular ectopy or NSVT runs following beta-blockade or amiodarone therapy does not imply a favourable diagnosis. Mortality was increased in the cardiac arrhythmia suppression trials (CAST and CAST II), despite reduced ectopic activity,44,45 whereas mortality was not reduced by amiodarone in the Veterans administration congestive heart failure survival trial of antiarrhythmic therapy (CHF-STAT) despite the elimination of ventricular ectopy.46

Nonsustained ventricular tachycardia can be detected in approximately 5% of ischaemic patients with preserved left ventricular function, apparently excluding previous myocardial infarction, but does not appear to indicate an adverse clinical outcome.47,48 However, NSVT appears now to occur in the majority of ischaemic patients with reduced left ventricular function,49,50 Induction of sustained arrhythmia by programmed electrical stimulation51,52 still appears to retain predictive power in ischaemic patients with impaired left ventricular function (LVEF<40%).50 Recently, the MUSTT investigators analysed the relation of ejection fraction and inducible ventricular tachyarrhythmias to mode of death in 1791 patients enrolled in MUSTT who had not already received antiarrhythmic therapy. Total and arrhythmic mortality were higher in patients with an ejection fraction <30% than in those whose ejection fractions were 30% to 40%. Inducibility of tachyarrhythmia identified patients for whom death was significantly more likely to be arrhythmic. This study therefore suggested that the major utility of electrophysiologic testing may be restricted to patients having an ejection fraction between 30% and 40%.50 In ischaemic patients with relatively well preserved left ventricular function (LVEF>40%), the role of programmed electrical stimulation is not established. There are cases, however, where programmed electrical stimulation tests may reveal monomorphic ventricular tachycardia in the postinfarction patient.

Noninducible patients may not have a lower risk for arrhythmic events. Both the MUSTT9 and the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II53 have suggested that patients noninducible by electrophysiologic testing have a risk for sudden cardiac death similar to that of inducible patients. In the MUSTT, the inducible group had a 2-year total mortality rate of 28%, whereas the noninducible group had 21%. The mortality rate in noninducible patients is high enough to question the need for programmed electrical stimulation. Actually, data from MADIT II suggest an even higher rate of appropriate ICD shocks in patients who were noninducible at electrophysiologic testing.53 These findings are consistent with analyses of stored ICD data, which have clearly shown that there was little association between spontaneous and induced ventricular arrhythmias.54 Thus, electrophysiology testing cannot select patients with a favourable outcome.

The value of signal-averaged ECG and autonomic markers, such as heart rate variability and depressed baroreflex sensitivity, for determining prognosis and selecting high-risk patients with NSVT is not established.3,40 Analysis of ATRAMI patients has shown that NSVT, heart rate variability, and depressed baroreflex sensitivity were all significantly and independently associated with increased mortality. Depressed baroreflex sensitivity, in particular, identified a subgroup with the same mortality risk as patients with NSVT and reduced LVEF.40 Recently, the Multiple Risk Factor Analysis Trial (MRFAT) showed that in the beta-blocking era the common arrhythmia risk variables, particularly autonomic and standard ECG markers, have limited predictive power in identifying patients at risk of sudden cardiac death.43 In a 43±15-month follow-up of 675 patients, sudden cardiac death was weakly predicted only by reduced LVEF (40%), NSVT, and abnormal signal-averaged ECG, but not by autonomic markers or ECG variables. The positive predictive accuracy of these markers (low LVEF, NSVT, and abnormal signal-averaged ECG), however, was low, 8%, 12%, and 13%, respectively.43 More data are clearly needed to establish the clinical utility of autonomic markers, particularly in the setting of NSVT.

Based on the MUSTT and MADIT results, patients with LVEF below 40% and NSVT should undergo electrophysiologic testing with a view to ICD implantation. Guided antiarrhythmic drug therapy no longer has a role in the treatment of these patients.55 Patients with LVEF less than 30% should be considered high-risk for arrhythmic death, regardless of the presence of NSVT, according to MADIT II. So far, no hard data exist to guide the management of ischaemic patients with NSVT and LVEF40%.

Nonischaemic heart disease
In conditions other than ischaemic heart disease the independent prognostic significance of NSVT, at least as far as sudden arrhythmic death is concerned, is even less established. There has been some evidence regarding its prognostic significance in patients with hypertrophic cardiomyopathy in the young,56,57 but several questions remain in patients with dilated cardiomyopathy46,58–60 and other congenital or idiopathic arrhythmogenic conditions.61–64 Clearly, more data are needed for risk stratification of these patients and ongoing trials are eagerly awaited in this respect.65,66

The high prevalence of ventricular arrhythmias on Holter monitoring in patients with dilated cardiomyopathy (up to 80%)46,58,60,67,68 makes their prognostic significance difficult to assess and the prognostic value of NSVT in this setting is questionable. The GESICA trial has provided evidence that in patients with NSVT the risk of sudden death compared to nonsudden death was significantly increased;59,60 this was not confirmed in the CHF-STAT.46 Furthermore, although amiodarone therapy was associated with decreased mortality in the GESICA trial, no such effect was observed in the CHF-STAT trial, despite the higher prevalence of NSVT in this cohort.60,46 No advantage of ICD implantation over amiodarone was shown in the AMIOVIRT trial in patients with LVEF35% and NSVT,69 despite suggestions that NSVT patients may require an ICD as badly as patients with a history of previous ventricular fibrillation.70 Similarly, disappointing results with the use of ICDs for primary prevention in patients with nonischaemic cardiomyopathy (LVEF30%) have been recently reported by the CAT investigators.71

The Marburg Cardiomyopathy Study72 has recently reported on noninvasive arrhythmia risk stratification in patients with dilated cardiomyopathy. Although NSVT and frequent ventricular premature beats showed a significant association with a higher arrhythmia risk on univariate analysis, on multivariate analysis only LVEF was found to be a significant predictor of major arrhythmic events with a relative risk of 2.3 per 10% decrease of LVEF. Signal-averaged ECG, baroreflex sensitivity, heart rate variability, and T-wave alternans were not helpful for arrhythmia risk stratification. Results of subanalyses from the still ongoing DEFINITE and SCD-HeFT trials should also provide data on the prognostic value of NSVT in this setting.

In hypertrophic cardiomyopathy 20–30% of patients may have NSVT, whereas in patients with a history of cardiac arrest this proportion approaches 80%.56,73,74 It has been suggested that NSVT only has prognostic importance in patients with hypertrophic cardiomyopathy when it is repetitive, prolonged, or associated with symptoms.3 In a recent study on 531 patients with hypertrophic cardiomyopathy, no relation between the frequency, duration, or rate of NSVT episodes could be demonstrated.57 However, NSVT was associated with a substantial increase in sudden death risk in young patients with hypertrophic cardiomyopathy.57 The presence of high-risk factors, including NSVT in the young, may justify defibrillator implantation as primary prevention in patients with hypertrophic cardiomyopathy.75

In cases of primary ventricular fibrillation, congenital long QT, and Brugada syndrome, the detection of NSVT on Holter or exercise testing has no predictive value to guide appropriate therapy, although ICD implantation is recommended, at least in symptomatic patients.61,63,76

In patients with valvular disease the incidence of NSVT is considerable (up to 25% in aortic stenosis and in significant mitral regurgitation) and appears to be a marker of underlying left ventricular pathology.77,78 Up to 65% of patients with surgical repair of tetralogy of Fallot have ventricular ectopy, whereas NSVT occurs in up to 17% of patients either at rest or during exercise.79,80 In patients with arterial hypertension, NSVT is correlated to the degree of cardiac hypertrophy and subendocardial fibrosis.81,82 Approximately 15% of patients with hypertension and left ventricular hypertrophy present NSVT, as opposed to 6% of patients with hypertension alone.81–83 No convincing evidence exists to prove that NSVT is an independent predictor of sudden death in patients with valve disease, repaired congenital abnormalities, or hypertension. In these conditions, therefore, the approach to the patient from the point of view of arrhythmias currently remains empirical.


    Conclusions
 Top
 Abstract
 Introduction
 Novel data on NSVT
 Clinical approach
 Conclusions
 References
 
Based on the evidence presented as well as on our own experience, we can make the following statements (Table 1).


View this table:
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Table 1 Clinical significance of NSVT

 
In the documented absence of heart disease, spontaneous NSVT does not appear to carry any adverse prognostic significance. Exercise-induced or postexercise NSVT may predict the future development of coronary artery disease and increased cardiac mortality.

In ischaemic patients with LVEF40%, NSVT has an adverse prognostic significance and electrophysiologic testing with a view to ICD implantation is indicated. In patients with LVEF40%, the independent prognostic significance of NSVT is unknown and the role of electrophysiologic testing not established, although we do advocate its use in this setting.

The independent prognostic value of NSVT in patients with dilated cardiomyopathy has never been proven. NSVT in patients with hypertrophic obstructive cardiomyopathy probably carries an adverse prognostic significance, particularly in the young.

The prognostic value of NSVT in conditions such as the long-QT syndromes, primary ventricular fibrillation, and Brugada syndrome, as well as in patients with hypertension and valvular disease, is not established.

Thus, the clinical approach to the patient with NSVT should always be considered within the particular clinical context in which the arrhythmia occurs.


    References
 Top
 Abstract
 Introduction
 Novel data on NSVT
 Clinical approach
 Conclusions
 References
 

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