A Case of Syncope due to Exercise Induced Ventricular Tachycardia

Questions and Answers


1. What are the identified common pathyphysiological mechanisms for ventricular premature beats? (Braunwald 8th edition chapter 31 pages 744-748)


1. Automaticity:  The ionic basis of automaticity is explained by a net gain in intracellular positive charges during diastole at a new site of depolarization in non-nodal ventricular tissue. Contributing to this change is a voltage-dependent channel (If : a hyperpolarization-activated inward pacemaker current) activated by potentials negative to -50 to -60mV.

2. Reentry: During a normal cardiac cycle, each cell becomes activated in turn, and the cardiac impulse dies out when all fibers have been discharged and are completely refractory (absolute refractory period). If, however, a group of fibers not activated during the initial wave of depolarization recover excitability in time to be discharged before the impulse dies out, they may serve as a link to reexcite areas that were just discharged and have now recovered from the initial depolarization. This typically occurs when slow-conducting tissue (eg, infarcted myocardium) is present adjacent to normal tissue.

3. Triggered Activity: Triggered activity is initiated by after-depolarizations which are depolarizing oscillations in membrane voltage induced by one or more preceding action potentials. These depolarizations can occur before or after full repolarization of the fiber, and are best termed early after-depolarizations (EAD’s) when they arise from a reduced level of membrane potential during phases 2 (type 1) and 3 (type 2) of the cardiac action potential, or are termed late or delayed after depolarizations (DAD’s) when they occur after completion of repolarization (phase 4).


2. Define frequent ventricular ectopy during exercise stress testing.


     Frequent ventricular ectopy is defined as the presence of seven or more ventriucular premature beats per minute during any given stage, ventricular bigeminy, ventricular trigeminy, ventricular coupletes, ventricular triplets, sustained or nonsustained ventricular tachycardia, ventricular flutter, torsades de pointes, or ventricular fibrillation.


3. Is frequent ventricular ectopy during recovery from exercise independently related to an increased risk of death from cardiovascular disease? Is frequent ventricular ectopy during exercise only an independent predictor? Substantiate your response.


     Frolkis et al (NEJM 2003:vol 348,no.9;781-790) conducted a prospective, observational study involving 29,244 patients who had been referred for symptom-limited exercise testing without a history of heart failure, valvular disease, or arrhythmia. Frequent ventricular ectopy occurred only during exercise in 3%, only during recovery in 2%, and during both exercise and recovery in 2%. Mean follow-up was 5.3 years, and the primary endpoint was death from all causes.

     After adjustment for baseline characteristics and variables associated with exercise stress testing, frequent ventricular ectopy only during exercise did not predict an increased risk of death (adjusted hazard ratio 1.2, CI 1.0-1.4), however frequent ventricular ectopy only during rest was a predictor of an increased risk of death (adjusted hazard ratio 1.6, CI 1.3-1.9). Other predictors for an increased risk of death included older age, male sex, insulin-treated diabetes mellius, smoking, impaired functional capacity, and attenuated heart-rate recovery (defined as failure of the heart rate to fall by more than 12 beats during the first minute after exercise, or 18 beats among patients undergoing stress echocardiography).

     Patients with more severe frequent ventricular ectopy (ventricular triplets, sustained or nonsustained ventricular tachycardia, ventricular flutter, torsade de pointes, or ventricular fibrillation) and those with less severe frequent ventricular ectopy (all other types of frequent ventricular ectopy) during recovery from exercise, had an increased risk of death (HR 2.1 and HR 1.5 for more severe and less severe ventricular ectopy, respectively).


4. What is the basis for the hypothesis as to why ventricular ectopy during recovery may be a stronger predictor of an increased risk of death than ectopy that occurred only during exercise?


     Vagal reactivation normally occurs in the early period of recovery immediately after exercise. In the absence of normal vagal reactivation, heart-rate recovery is attentuated with an associated increase in mortality. Therefore, attenuated vagal reactivation during recovery might be associated with ventricular ectopy that is not suppressed.


5. Does the morphology of frequent ventricular ectopy during exercise testing impact on patient prognosis?


     Yes (Annals of Int Med 2008;149: 451-60.)

     In a study of 585 patients with exercise induced ventricular ectopy ( EIVA) on treadmill stress testing and 2340 patients without EIVA matched for age, sex and risk factors, patients with LBBB morphology EIVA had a mortality rate of 2.5% over 4 years. This was not significantly different from patients without EIVA. In contrast, patients with RBBB morphology EIVA or multiple morphology EIVA had significantly increased 4-year mortality rates. In patients without known CAD, any RBBB morphology EIVA was associated with a significant death hazard ratio of 2.73 but LBBB morphology EIVA was not. The explanation offered is that LBBB morphology EIVA included many patients with benign idiopathic RVOT ectopy/tachycardia thus minimizing the overall prognostic significance of this morphology of EIVA.


6. In a young person, what is the differential diagnosis when faced with exercise-induced ventricular tachyarrhythmias?


a. Structural abnormalities: hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, coronary artery anomalies, myocarditis, dilated cardiomyopathy, early-onset atherosclerosis.

b. Primary electrical diseases without manifest structural heart disease: Brugada syndrome, long QT syndrome, short QT syndrome, catecholminergic polymorphic ventricular tachyarrhythmia, WPW, commotio cordis.


7. Describe the ways by which one can differentiate HCM from athlete’s heart.


     HCM is a cardiac disease of autosomal dominant inheritance, defined as an asymmetrically hypertrophied non-dilated left ventricle which may result in obstruction of the left ventricular outflow tract (the most common variant however is asymmetric septal hypertrophy without obstruction). Sudden cardiac death is caused by electrically unstable cardiac tissue that has generated reentrant ventricular tachyarrhythmias.

     The classic finding on physical exam is a systolic ejection murmur heard best at the apex, that becomes louder with Valsalva or with standing from a squatting position.

     -ECGs will be abnormal in 75-95% of patients with HCM and may include LV hypertrophy, conduction defects, and pseudoinfarct patterns.

     -Echo is the gold standard for the diagnosis, and will show asymmetric hypertrophy and a nondilated LV. Typically, the walls are >15mm, and the outflow tract may become obstructed during systole.


     The athlete’s heart is caused by physiologic, benign adaptations to systematic training, resulting in LV hypertrophy. A modest hypertrophy of the ventricular walls can be seen, with LV walls < 13mm in 98% of males with athlete’s heart. The other 2% may have walls of 13-15mm, falling into the so-called “grey zone”.


When the wall thickness falls into the “grey zone” of 13-15mm, other diagnostic characteristics may be of use:


Athlete’s Heart

Hypertrophic Cardiomyopathy

LV cavity > 55mm

LV cavity < 45 mm

Max VO2 > 45ml/kg/min or >110% predicted

Unusual patterns of LV hypertrophy

Decrease in thickness with deconditioning

Bizarre ECG patterns


Marked LA enlargement


Abnormal LV filling


Female gender


Family history of HCM


CMR evidence or gadolinium delayed enhancement.

From Postgraduate medicine. Volume 122, Issue 4, July 2010, page 147.


8. What treatment and recommendations can be offered to patients with HCM.

American College of Cardiology/European Society of Cardiology Clinical Expert Consensus Document on Hypertrophic Cardiomyopathy. European Heart Journal (2003) 24, 1965–1991).


a) Beta blockers are first-line therapy for HCM patients with symptomatic outflow obstruction. The beneficial effects of beta-blockers on symptoms of exertional dyspnea and exercise intolerance appear to be attributable largely to a decrease in the heart rate with a consequent prolongation of diastole and an increase in passive ventricular filling. These agents lessen LV contractility and myocardial oxygen demand and possibly reduce microvascular myocardial ischemia.

     Substantial experience suggests that standard dosages of these drugs can mitigate disabling symptoms and limit the latent outflow gradient provoked during exercise when sympathetic tone is high and heart failure symptoms occur. However, there is little evidence that beta-blocking agents consistently reduce outflow obstruction under resting conditions. Consequently, beta-blockers are a preferred drug treatment strategy for symptomatic patients with outflow gradients present only with exertion.


b) Verapamil has been widely used empirically in both the nonobstructive and obstructive forms, with a reported benefit for many patients, including those with a component of chest pain. Verapamil in doses up to 480 mg per day has favorable effects on symptoms by improving ventricular relaxation and filling as well as relieving myocardial ischemia and decreasing LV contractility. However, Verapamil may cause adverse hemodynamic effects due to its vasodilating properties, resulting in augmented outflow obstruction, pulmonary edema, and cardiogenic shock. Therefore, caution should be exercised in administering verapamil to patients with resting outflow obstruction and severe limiting symptoms.


c) Disopyramide is a negative inotropic and Type I-A antiarrhythmic agent. There are

reports of disopyramide producing symptomatic benefit (at 300 mg to 600 mg per day with a dose-response effect in severely limited patients with resting obstruction, because of a decrease in SAM, outflow obstruction, and mitral regurgitant volume. Because

disopyramide may cause accelerated atrioventricular nodal conduction and thus increase ventricular rate during AF, supplemental therapy with beta-blockers in low doses to achieve normal resting heart rate has been advised.


d) Myomectomy is indicated if LVOT obstruction occurs and if angina, dyspnea and/or syncope has significantly reduced the quality of life and if these symptoms are persistent despite medical therapy.  Observational data suggests that HCM-related and SCD mortality rates are better than expected after myomectomy.


e) Alcohol-induced septal ablation: indicated if LVOT obstruction is present, if symptoms persist despite medical therapy, if the patient is a suboptimal surgery candidate, and if the patient prefers it. The chance of procedural complications is greater for ablation compared to myectomy. Patients ≤65 years have better symptom resolution with myectomy. Although no impairment in short-term survival was seen with ablation, its long-term effects are still unknown.


f) Anticoagulation for atrial fibrillation.


g) Genetic testing and family screening (first-degree relatives).


h) Counselling to avoid competitive sports, although these patients may cautiously attempt class IA competitive sports (includes golf, bowling and billiards).


i) Implantable Defibrillator: should be implanted as secondary prevention for patients with a history of cardiac arrest or sustained ventricular tachycardia. The ICD should be considered as primary prevention for patients with 1 or more risk factors: family history of sudden death; syncope; extreme LVH (³ 3cm maximum wall thickness); hypotensive blood pressure response to exercise; and non-sustained VT (on holter monitor).


9. Describe the typical resting ECG and arrhythmia characteristics of ARVD.

(Westrol et al. Causes of sudden cardiac arrest in young athletes. Postgraduate Medicine. Volume 122, issue 4. July 2010).


ARVD is a myocardial disease that is familial in approximately 50% of cases and is usually inherited as an autosomal dominant trait. The prevalence is 1 in 1000 to 1 in 5000. It is responsible for approximately 2.7% of sudden cardiac deaths in young athletes in the United States (up to 10.1% in the UK). ARVD is due to fibro-fatty tissue replacement of the RV myocardium leading to wall thinning and aneurysms, which interfere with the conduction system leading to ventricular arrhythmias.


Major ECG criteria:

-Epsilon waves in V1-V3.

-Localized prolongation of the QRS complex >110ms in leads V1-V3.

-Any arrhythmias in minor criteria + inverted T waves in V2 and V3.


Minor ECG criteria:

-Late potentials in a signal-averaged ECG.

-inverted T waves in right precordial leads in absence of RBBB.

-LBBB-type VT (sustained or non-sustained) found on ECG, Holter, or exercise stress testing. Frequent ventricular extrasystoles (>1000 in 24 hours) on Holter monitoring.


10. In the Brugada syndrome, describe the rest and exercise electrocardiograms.

(Exercise-induced ECG changes in the Brugada syndrome: Ahamad et al. Circ Arrhythmia Electrophysiology. 2009;2:531-539).


Rest: lower heart rates, prolonged QRS intervals, decreased QTc durations, and right precordial peak J-point elevation (with descending, coved ST elevation in the type 1 pattern). Of note, ST elevation is restricted to V1-V3 in the Brugada syndrome. In “benign” early repolarization, ST elevation is more widespread with the greatest amplitude of ST elevation is in V4-V5. In the SCN5A+ phenotype of Brugada syndrome, there may be PR prolongation in addition to the other features.


Exercise: PR shortening (to the same extent as in healthy control subjects), QRS widening (seen in Brugada syndrome SCN5A+ phenotype), QT shortening (but to a lesser extent than in control subjects, leading to QTc lengthening at peak exercise), and augmentation of precordial peak J-point elevation, which reaches its maximum amplitude during the early phase of recovery from exercise. Typically the peak J-point elevation in V1 or V2 exceeds 2 mm or more at peak exercise or early recovery. In normals, any J-point elevation in V1 or V2 at peak exercise is less than 1 mm. Additionally, in normals,  any J-point augmentation in V1-V2 at peak exercise invariably goes down in early recovery. In normal patients with “benign” early repolarization, the affected leads to the left of V1-V2  show a reduction or disappearance of ST elevation with exercise.