Nonsustained VT during ExerciseTesting-Causes and Work-Up

David Lin, MD David J. Callans, MD, From theElectrophysiology Section, Division of CardiologyUniversity of Pennsylvania Health System,Philadelphia, Pennsylvania

Exercise stress testing is a well-established procedure thathas been in widespread clinical use for several decades.While the predictive value of ischemic changes duringstress testing is well established, uncertainty remains as towhether the development of ventricular premature depo-larizations before, during or after exercise has prognosticvalue, especially in asymptomatic patients without knownor suspected coronary artery disease. A review of previouslypublished studies evaluating exercise-induced ventricularectopic activity has demonstrated an association with ad-vanced age, the presence of coronary artery disease, leftventricular dysfunction and prior aborted sudden cardiacdeath or malignant ventricular arrhythmias. Several studieshave addressed the question of the prognostic value ofexercise-induced ventricular ectopy with regard to subse-quent cardiac events and mortality. In many of these stud-ies, however, the study population involved select groups,either high-risk groups that are post-myocardial infarction,including patients post sudden cardiac death or low-riskgroups involving asymptomatic, healthy volunteers. Thepresence of exercise-induced ventricular ectopy was shownto have an association with higher subsequent mortality inthe post sudden cardiac death groups. However, this resulthas not been a consistent finding in other similar studies.

Prognostic Implications of NSVT During ExerciseTestingContrary to the post sudden cardiac death group, studies ofasymptomatic volunteers have almost uniformly demon-strated no clear association between exercise-induced ven-tricular ectopy and mortality. In a study performed by Fleget al., an analysis of 597 male and 325 female volunteersfrom the Baltimore Longitudinal Study on Aging who werewithout apparent heart disease, the prevalence of non-sustained ventricular tachycardia (NSVT) was approxi-mately 1% of subjects during maximal treadmill exercise.Over a 2-year period of observation, exercise-inducedNSVT in apparently healthy subjects did not portend in-creased morbidity or mortality rates. The discrepancy in thepublished results may in part be explained by the rigor withwhich coronary artery disease is excluded in the individualstudies. This review will address the causes, work-up andprognosis of exercise-induced NSVT.

The definition of NSVT varies in the available literature.Most studies define NSVT as three or more consecutive

premature ventricular beats at a rate greater than 100 beatsper minute, lasting no more than 30 seconds in duration.Exercise-induced myocardial ischemia has been proposedas one of the potential causes of NSVT observed duringexercise. Increased myocardial oxygen demand due to anincrease in heart rate, contractility or afterload and vasocon-striction, thrombosis or plaque rupture due to shear stresscan also lead to reduced oxygen supply and thus contributeto myocardial ischemia. Exercise causes a withdrawal ofvagal tone and an activation of the sympathetic nervoussystem, resulting in an increase in circulating cat-echolamines. Circulating levels of epinephrine and norepi-nephrine have been shown to continue to increase duringthe first 3 minutes after exercise, and in part, may explainthe occurrence of ventricular arrhythmias seen post-exer-cise. In 1994, Imai et al. hypothesized that vagal reactiva-tion was an important mechanism for cardiac decelerationafter exercise. Vagally mediated recovery of heart rate postexercise was assessed in 20 patients with chronic heartfailure and in nine well-trained athletes by analyzing theheart rate decay after exercise. The time constants of thebeat-by-beat heart rate decay for the first 30 seconds andthe first 120 seconds after exercise were obtained at sixlevels of exercise. They found that vagally mediated heartrate recovery after exercise is accelerated in well-trainedathletes but blunted in patients with chronic heart failure.Furthermore, several other recent studies have corrobo-rated this finding that in the absence of normal vagal reac-tivation, heart rate recovery is attenuated, with an associ-ated increase in mortality. It was on the basis of thesefindings that Frolkis et al. in a recent publication suggestedthat frequent ventricular ectopy after exercise may be abetter predictor of death than ectopy observed during ex-ercise. They evaluated a total of 29,244 patients who hadbeen referred for symptom-limited exercise testing withouta history of heart failure, valve disease or arrhythmia. Fre-quent ectopy was defined in this particular study by thepresence of seven or more ventricular premature beats perminute, encompassing ventricular bigeminy or trigeminy,ventricular couplets or triplets, ventricular tachycardia,ventricular flutter, torsade de pointes or ventricular fibril-lation. In that cohort of patients, 3% (945 patients) hadfrequent ventricular ectopy only during exercise, 2% (589patients) only during recovery and 2% (491 patients) dur-ing both exercise and recovery. Their analysis involved amean follow-up of 5.3 years during which time there were1862 deaths. Frequent ventricular ectopy during recoveryfrom exercise was found to be an important, independentpredictor of an increased risk of death. Frequent ventricularectopy that occurred only during exercise did not indepen-dently predict an increased risk. These results support thefundamental importance of vagal mediation in cardiac

ACC CURRENT JOURNAL REVIEW Nov/Dec 2003© 2003 by the American College of Cardiology Foundation 1062-1458/03/$30.00Published by Elsevier Inc. doi:10.1016/j.accreview.2003.09.06857

ArrhythmiasFocused Review

function and are in agreement with the previous findings ofa strong relation between attenuated recovery of the heartrate after exercise and an elevated risk of death. The prog-nosis of ventricular arrhythmias in patients with no struc-tural heart disease and in the absence of coronary arterydisease carries with it a different outcome when comparedto ventricular arrhythmias in the setting of coronary arterydisease.

Idiopathic Ventricular TachycardiaThere are several ventricular tachyarrhythmia syndromesthat can occur in the absence of structural heart disease.These tachycardias are frequently provoked during exercisetesting. Unlike VT that occurs in the setting of advancedstructural heart disease, idiopathic VT often responds todrugs that, in ischemic VT, either lack efficacy or may evenbe contraindicated. Furthermore, unlike ischemic VT, idio-pathic VT carries an excellent prognosis both from thestandpoint of freedom from arrhythmic death or develop-ment of structural heart disease. The most common type ofidiopathic VT originates in the right ventricular outflowtract (RVOT). Another less common form, often referred toas fascicular VT, originates from the inferobasal left ventric-ular septum. Several studies have provided evidence thatRVOT ventricular tachycardia in patients with structurallynormal hearts is adenosine sensitive and due to catechol-amine-mediated delayed afterdepolarizations and triggeredactivity. On the other hand, idiopathic left ventriculartachycardia is often caused by reentry.

Repetitive monomorphic ventricular tachycardia, origi-nally described by Gallavardin in 1922 as a type of idio-pathic VT characterized by short bursts of monomorphicVT, most commonly originates in the outflow tract of theright ventricle. Right ventricular outflow tract (RVOT)tachycardia, also referred to as catecholamine-sensitive VTor exercise-induced VT, as the name suggests, is triggered

by exercise or any physiologic state that can cause a surge incatecholamine levels. There does not appear to be genderspecific predilection. However, in one series involving fe-males with RVOT tachycardia, there appeared to be positivecorrelation with the menstrual cycle.

Although the presence of ventricular ectopy and NSVTin patients without structural heart disease has a benigncourse, the reality is that many patients can experiencedebilitating symptoms. To put things in perspective, areport by Krittayaphong et al. showed that the quality of lifescores in patients with ventricular arrhythmias are at thesame level as those of patients with severe rheumatic mitralstenosis and acute coronary syndromes.

RVOT tachycardia has some very distinct electrocardio-graphic features that assist in its diagnosis. Because it arisesin the outflow tract, the QRS morphology is left bundlebranch with an inferiorly directed axis (Figure 1). Based onextensive experience with catheter ablation and the wealthof information garnered from mapping these tachycardias,these tachycardias can be localized to specific regions of theoutflow tract based on the 12-lead ECG morphology.

Workup of the patient with idiopathic VT involves rul-ing out structural heart disease. A normal signal averagedelectrocardiogram (SAECG) is useful in excluding rightventricular dysplasia. Non-invasive imaging studies such asechocardiography and nuclear imaging studies are usefulfor evaluating ventricular function and the presence ofischemia. In idiopathic VT, ventricular function is normalexcept in rare circumstances where frequent episodes oftachycardia may result in a tachycardia-mediated cardio-myopathy. Coronary angiography is useful in excluding VTsecondary to structural heart disease if the suspicion is highand if the electrocardiogram (ECG) does not localize the siteof origin to the outflow tract. However, in the majority ofidiopathic VTs, noninvasive imaging modalities, in con-junction with characteristic findings on surface ECG, are

Figure 1. Repetitive monomorphic VT arising from the RV outflow tract. The ECG is characteristic (left bundle, inferior axis) as is the presentation with “salvoes” of NSVT.

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sufficient in localizing those originating from the RV orLVOT. Exercise stress testing is very useful in provokingventricular tachycardia because these VTs are often cate-cholamine dependent. Documentation of the ventriculartachycardia on 12-lead ECG is useful in identifying whicharea of the heart to target during ablative therapy. Further-more, the characteristics of the VT and its response toexercise may also shed light on the best modality of therapy.

Krittayaphong et al. performed a study evaluating the1-year outcome after radiofrequency catheter ablation ofsymptomatic ventricular arrhythmias originating in theright ventricular outflow tract. A total of 34 patients withventricular arrhythmia with a typical left bundle branchmorphology and an inferior axis, compatible with RVOTorigin, were evaluated. These patients were all highly symp-tomatic (palpitations, presyncope or syncope) with greaterthan 100 PVCs per hour and had no evidence of structuralheart disease documented by normal echocardiogram andexercise testing. Exercise-induced ventricular arrhythmiawas defined as an increase in the number of prematureventricular beats or the appearance of more malignantforms of ventricular arrhythmia during exercise and wasdemonstrated in 30% of the patients. These patients under-went radiofrequency ablation with an overall success rate of97%, defined as complete elimination of ventricular ar-rhythmias 30 minutes after the procedure. They found thatquality-of-life scores were significantly improved at 1month and up to 12 months after the procedure. Even thepatients with recurrence (eight patients) who still hadgreater than 1000 PVCs per 24 hours described an im-provement in symptoms.

It is important to emphasize that ventricular ectopy andfrequent ventricular arrhythmias in patients without struc-tural heart disease carry a good prognosis in general. In rarecircumstances, polymorphic ventricular tachycardia andtorsade de pointes caused by various genetic or acquiredcardiac abnormalities, such as ion-channel abnormalities,acquired long-QT syndrome or left ventricular hypertrophycan contribute to the initiation of life-threatening arrhyth-mias. The spectrum of symptoms may range from none atall, to palpitations, to more serious symptoms includingpresyncope and syncope. The more severe symptoms mayperhaps be explained by unrecognized episodes of sus-tained arrhythmia. Given the relatively benign course ofventricular arrhythmia in this population, the goal of anytherapy is not to prolong life, but rather, to alleviate symp-toms and to improve quality of life.

In patients who present with ventricular arrhythmiasduring exercise, it is important to evaluate the underlyingsubstrate. The workup varies from institution to institutionand from practitioner to practitioner. In our practice, stan-dard 2D echocardiography and exercise stress testing isperformed. Magnetic resonance imaging is obtained if thereis a high suspicion of right ventricular dysplasia. The pres-ence of multiple left bundle VT morphologies should sug-gest the possibility of arrhythmogenic right ventricular dys-

plasia (ARVD). Signal averaged ECG (SAECG) is anotheruseful diagnostic tool for ARVD if late potentials and frac-tionated electrograms are recorded. In the SAECG, high-gain amplification and filtering enables the detection ofsmall potentials in the terminal part of the QRS complexthat are thought to reflect the presence of latent substratesfor ventricular tachycarrhythmias. In most studies utilizingSAECG, the main limitation of the SAECG has been therelatively low positive predictive accuracy. However, thenegative predictive value of normal findings on SAECG inpatients who have had prior myocardial infarction andscarring has been demonstrated to be excellent. More re-cently, the availability of the electroanatomic mapping hasprovided the ability to record local electrogram voltage tocreate a map defining areas of scar, border zone and healthynormal tissue. Although the electroanatomic mapping cri-teria for ARVD have not been defined, areas of low voltageconsistent with scarring are useful and in the appropriateclinical context can be confirmatory. Invasive electrophys-iological evaluation for diagnosing RVOT tachycardia isgenerally not necessary.

SummaryThe development of new approaches or techniques that willallow screening for markers of increased risk of suddencardiac death in large unselected populations remains thechallenge for the future. The role of genetic screening orother noninvasive markers yet to be developed remains tobe realized. At present, it can probably be concluded thatNSVT on stress testing, especially in the recovery period, isan independent predictor of overall mortality but not nec-essarily of sudden death. This negative prognosis cannot beapplied to patients without structural heart disease whohave idiopathic VT or NSVT with exercise. Idiopathic VT isrecognized by characteristic electrocardiographic featuresin the absence of structural heart disease. In the absence ofstructural heart disease, beta-blockers and calcium channelblockers remain the mainstay of therapy. In patients withrecurrent symptoms or patients intolerant of medications,radiofrequency energy ablation offers a highly effective al-ternative therapeutic option.

Questions and Answers

1. What are some of the physiologic effects of exercise onarrhythmogenesis?

One of the main physiologic changes that takesplace during exercise that may contribute to arrhyth-mogenesis is sympathetic nervous system activationand withdrawal of vagal tone resulting in an increasein catecholamine circulation. Furthermore, there maybe some degree of ischemia that can take place on acellular level that can alter the membrane action po-tential.

2. What are some of the electrocardiographic features ofRVOT tachycardia?

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The electrocardiogram is left bundle morphologywith an inferiorly directed axis. The transition of theQRS complex in the precordial leads from negative topositive generally occurs at lead V3 to V4. If thetransition occurs before V3, the tachycardia likelyoriginates from the left ventricular outflow tracttachycardia.

3. What is the prognosis of NSVT and what should theevaluation entail?

The prognosis depends on the presence or absenceof structural heart disease. In the absence of heartdisease, NSVT does not portend an increase in the riskof sudden death. As such, it is important to obtain anechocardiogram to assess the ventricular function.Exercise stress testing with nuclear imaging is usefulboth to rule out ischemia and to assess the response ofthe NSVT to exercise. Electrocardiographic signaturesare helpful in diagnosing RVOT tachycardia.

4. What are the treatment options available for idio-pathic VT in a structurally normal heart?

Beta-blockers and calcium channel blockers (vera-pamil and diltiazem) are the mainstay of therapy. Inpatients who remain symptomatic despite medicaltherapy or who have contraindications and intoler-ance of medications, radiofrequency ablative therapyoffers an excellent and efficacious alternative thera-peutic modality.

5. What is the incidence of ventricular arrhythmia in thegeneral population referred for exercise stress testing?

The incidence ranges from 1 to 4% depending onthe population involved. Age (higher incidence withage �50), presence or absence of underlying heartdisease, previous history of sustained ventricular ar-rhythmia and gender will determine the likelihood ofventricular tachyarrhythmias.

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Fleg J, Tzankoff S, Lakatta E. Age-related augmentation of plasmacatecholamines during dynamic exercise in healthy males.J Appl Physiol 1985;59:1033–9.

Dimsdale J, Hartley L, Guiney T, Ruskin J, Greenblatt D. Post-exercise peril: plasma catecholamines and exercise. JAMA1984;251:630–2.

Callans DJ, Menz V, Schwartzman D, et al. Repetitive monomor-phic tachycardia from the left ventricular outflow tract: Elec-trophysiologic patterns consistent with a left ventricular site oforigin. J Am Coll Cardiol 1997;29:1023–7.

Buxton AE, Waxman HL, Marchlinski FE, et al. Right ventriculartachycardia: Clinical and electrophysiological characteristics.Circulation 1983;68:917–27.

Lerman BB, Stein K, Engelstein ED, et al. Mechanism of repetitivemonomorphic ventricular tachycardia. Circulation 1995;92:421–9.

Hayashi H, Fujiki A, Tani M, et al. Role of sympathovagal balancein the initiation of idiopathic vantricular tachycardia originat-ing from the right ventricular outflow tract. Pacing Clin Elec-trophysiol 1997;20:2371–7.

Imai K, Sato H, Hori M, Kusuoka H, Ozaki H, Yokoyama H,Takeda H, Inoue M, Kamada T. Vagally mediated heart raterecovery after exercise is accelerated in athletes but blunted inpatients with chronic heart failure. J Am Coll Cardiol 1994;24:1529–35.

Frolkis J, Pothier C, Blackstone E, Lauer M. Frequent VentricularEctopy after Exercise as a Predictor of Death. N Engl J Med2003;348:781–90.

Krittayaphong R, Sriratanasathovorn C, Bhuripanyo K, Raungra-tanaamporn O, Soongsawang J, Khaosa-ard B, Kangkagate C.One-year outcome after radiofrequency catheter ablation ofsymptomatic ventricular arrhythmia from right ventricularoutflow tract. Am J Cardiol 2002;89:1269–74.

Address correspondence and reprint request to David J. Cal-lans, MD, 9 Founders Pavilion, Hospital of the University ofPennsylvania, 3400 Spruce Street, Philadelphia, PA 19104.

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