Exercise-induced Ventricular Arrhythmias In Patients Research Articles

The prognostic value of exercise-induced ventricular arrhythmias in patients with and without coronary artery disease: A meta-analysis

BackgroundSignificance of exercise-induced ventricular arrhythmias (EIVAs) is controversial. This meta-analysis aimed to determine the prognostic value of EIVAs in patients with and without coronary artery disease (CAD). MethodsRelevant studies were searched on Pubmed though December, 2015. Pooled odds ratio (OR) of endpoints (all-cause death, cardiac death or cardiac events) for all included studies was calculated at first to explore the significance of EVIAs in unselected population. Then, sensitivity analysis based on CAD status of population was performed to determine ORs of endpoints in CAD population, non-CAD population and mixed population, respectively. ResultsA total of 14 studies examining 23,002 patients were included, with 5 studies involved CAD population, 4 involved non-CAD population, and 5 involved mixed population (%CAD ranged from 51.2% to 76.8%). EIVAs in unselected population were associated with a pooled OR of 1.626 (95%CI 1.334 to 1.983, p<0.001) of endpoints when compared with those without EIVAs. Sensitivity analysis further indicated that pooled ORs of endpoints were 1.395 (95%CI 1.061 to 1.833, p=0.017) in CAD population, 1.933 (95%CI 1.567 to 2.384, p<0.001) in non-CAD population, and 1.402 (95%CI 1.198 to 1.640, p<0.001) in mixed population. Heterogeneous among studies was identified. Meta-regression analysis found that study quality, mean follow-up period, percentage of lost, percentage of diabetes were associated with ORs of endpoints. ConclusionsEIVAs were associated with increased risk of worse outcomes, no matter the patients had CAD or not. However, more studies are required to confirm this finding due to the variation of current evidences.

Electrocardiographic patterns of exercise-induced ventricular arrhythmias in patients with and without coronary artery disease

Objectives: This study was carried out to compare the electrocardiographic characteristics of exercise-induced ventricular arrhythmias (EIVA) in patients with and without coronary artery disease (CAD). Methods: The exercise tests of patients who were diagnosed to have EIVA and also underwent coronary angiography were analyzed retrospectively. The electrocardiographic patterns of EIVA in patients with and without CAD were compared. Results: The most common EIVA was premature ventricular contractions (PVCs) with left bundle-branch block (LBBB) pattern and inferior axis in both groups (63% in normal coronary artery (NCA) group and 59% in CAD group). PVCs with right bundle-branch block (RBBB) pattern and superior axis (33% vs. 17%, p=0.001) and the presence of multifocal PVC were found to be more frequent in CAD group (23% vs. 7%, p

Flecainide therapy suppresses exercise-induced ventricular arrhythmias in patients with CASQ2-associated catecholaminergic polymorphic ventricular tachycardia

Calsequestrin-associated catecholaminergic polymorphic ventricular tachycardia (CPVT2) can cause sudden death in young individuals in response to stress. Beta-blockers are the mainstay medical treatment for patients with CPVT2. However, they do not prevent syncope and sudden death in all patients. Flecainide was reported to reduce exercise-induced ventricular arrhythmias (EIVA) in patients with ryanodine receptor-associated CPVT. The role of flecainide in CPVT2 is not known. To summarize our experience in combining flecainide and beta-blockers in high-risk patients with CPVT2. All patients with CPVT2 (10 patients) who have high-risk features (syncope, EIVA, or appropriate implantable cardioverter-defibrillator [ICD] shocks) despite beta-blockers with or without calcium channel blockers were treated with a combination of flecainide and beta-blockers. Exercise test was done before and after beginning treatment with flecainide. All patients had EIVA and 4 had appropriate ICD shocks before flecainide treatment. EIVA-included frequent ventricular premature beats and or ventricular tachycardia during the exercise test while on high dose of beta-blockers with or without calcium channel blockers before treatment with flecainide. After combination therapy with flecainide and beta-blockers, EIVA were suppressed completely in all patients. During follow-up of 15.5 ± 10.4 months (range 2-29 months), 8 patients were free of symptoms and free of arrhythmias. Two patients had 1 VT storm episode with recurrent ICD shocks despite repeated normal stress test. Flecainide can completely prevent ventricular arrhythmia during exercise and partially prevent recurrent ICD shocks in high-risk patients with CPVT2.

Flecainide Therapy Reduces Exercise-Induced Ventricular Arrhythmias in Patients With Catecholaminergic Polymorphic Ventricular Tachycardia

This study evaluated the efficacy and safety of flecainide in addition to conventional drug therapy in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT). CPVT is an inherited arrhythmia syndrome caused by gene mutations that destabilize cardiac ryanodine receptor Ca(2+) release channels. Sudden cardiac death is incompletely prevented by conventional drug therapy with β-blockers with or without Ca(2+) channel blockers. The antiarrhythmic agent flecainide directly targets the molecular defect in CPVT by inhibiting premature Ca(2+) release and triggered beats in vitro. We collected data from every consecutive genotype-positive CPVT patient started on flecainide at 8 international centers before December 2009. The primary outcome measure was the reduction of ventricular arrhythmias during exercise testing. Thirty-three patients received flecainide because of exercise-induced ventricular arrhythmias despite conventional (for different reasons, not always optimal) therapy (median age 25 years; range 7 to 68 years; 73% female). Exercise tests comparing flecainide in addition to conventional therapy with conventional therapy alone were available for 29 patients. Twenty-two patients (76%) had either partial (n = 8) or complete (n = 14) suppression of exercise-induced ventricular arrhythmias with flecainide (p < 0.001). No patient experienced worsening of exercise-induced ventricular arrhythmias. The median daily flecainide dose in responders was 150 mg (range 100 to 300 mg). During a median follow-up of 20 months (range 12 to 40 months), 1 patient experienced implantable cardioverter-defibrillator shocks for polymorphic ventricular arrhythmias, which were associated with a low serum flecainide level. In 1 patient, flecainide successfully suppressed exercise-induced ventricular arrhythmias for 29 years. Flecainide reduced exercise-induced ventricular arrhythmias in patients with CPVT not controlled by conventional drug therapy.

Exercise-Induced Ventricular Arrhythmias in Patients with No Structural Cardiac Disease

We review the clinical and genetic disorders associated with exercise-induced ventricular arrhythmias in patients with normal hearts. Foremost are those with catecholaminergic polymorphic ventricular tachycardia due to abnormalities in either the ryanodine receptor 2 genes (RyR2) or the calsequestrin genes (CASQ). These patients manifest ventricular premature beats and polymorphic ventricular tachycardia in response to exercise or on exposure to catecholamines. A great deal of basic information has been accumulated suggesting that these arrhythmias are caused by abnormalities in Ca2+ metabolism. The ensuing cytosolic Ca2+ overload results in delayed after-depolarizations and extrasystolic Ca2+ waves, leading to polymorphic ventricular tachycardia. Most of these patients will respond to beta-blocker therapy but a significant minority (30%) will require a defibrillator. Advances in genetic testing allow better understanding of this syndrome.

Calcium Channel Antagonism Reduces Exercise‐Induced Ventricular Arrhythmias in Catecholaminergic Polymorphic Ventricular Tachycardia Patients with RyR2 Mutations

Calcium channel antagonism in RyR2 defects. Recently, gain-of-function mutations of cardiac ryanodine receptor RyR2 gene have been identified as a cause of familial or catecholaminergic polymorphic ventricular tachycardia. We examined the influence of the calcium channel blockers, verapamil and magnesium, on exercise-induced ventricular arrhythmias in patients with RyR2 mutations. Six molecularly defined catecholaminergic polymorphic ventricular tachycardia patients, all carrying a RyR2 mutation and on beta-adrenergic blocker therapy, underwent exercise stress test four times: at baseline, after verapamil and magnesium sulphate infusions, and finally, without interventions. The number of isolated and successive premature ventricular complexes during exercise ranged from 40 to 374 beats (mean 165 beats) at baseline, and was reduced during verapamil by 76+/-17% (P<0.05). Premature ventricular complexes appeared later and at higher heart rate during verapamil than at baseline (119+/-21 vs. 127+/-27 min-1, P<0.05). Magnesium did not inhibit the arrhythmias. Results in the fourth exercise stress test without interventions were similar to those in the first baseline study. This study provides the first in vivo demonstration that a calcium channel antagonist, verapamil, can suppress premature ventricular complexes and nonsustained ventricular salvoes in catecholaminergic polymorphic ventricular tachycardia caused by RyR2 mutations. Modifying the abnormal calcium handling by calcium antagonists might have therapeutic value.

Functional and prognostic significance of exercise-induced ventricular arrhythmias in patients with suspected coronary artery disease

Our aims were to assess (1) the relation between exercise-induced ventricular arrhythmia (VA) and myocardial wall motion abnormalities during exercise echocardiography in patients with suspected coronary artery disease (CAD), and (2) the effect of this relation on outcome. We studied the clinical and prognostic significance of exercise-induced VA in 1,460 patients (mean age 64 ± 10 years; 867 men) with intermediate pretest probability of CAD and no history of previous myocardial infarction or revascularization who underwent exercise echocardiography. Exercise-induced VA occurred in 146 patients (10%). Compared with patients without VA, those with VA had a greater prevalence of abnormal exercise echocardiographic findings (48% vs 29%, p = 0.001) and ischemia on exercise echocardiography (39% vs 22%, p = 0.001), greater increase in wall motion score index with exercise (0.14 ± 0.28 vs 0.06 ± 0.18, p <0.0001), and a greater percentage of abnormal segments with exercise (21 ± 30% vs 9 ± 19%, p <0.0001). During follow-up (median 2.7 years), cardiac death and nonfatal myocardial infarction occurred in 36 patients. In multivariate analysis of combined clinical and exercise stress test variables, independent predictors of cardiac events were exercise-induced VA (chi-square 4.7, p = 0.03) and exercise heart rate (chi-square 18, p = 0.0001). The percentage of abnormal myocardial segments with exercise echocardiography was the most powerful predictor of VA (chi-square 31, p = 0.0001) and cardiac events (chi-square 15, p = 0.0001). In patients with suspected CAD, exercise-induced VA is associated with a greater risk of cardiac death and nonfatal myocardial infarction. This risk is attributed to the relation between VA and the extent and severity of left ventricular functional abnormalities with exercise.

Exercise-induced ventricular arrhythmias in patients with healed myocardial infarction

Background: Controversy exists about the clinical and prognostic significance of exercise-induced ventricular arrhythmias late after myocardial infarction. The aim of the study was to identify the main clinical and prognostic features of exercise-induced ventricular arrhythmias in out-patients with healed Q-wave myocardial infarction. Methods: The study population was 777 consecutive patients who underwent a symptom-limited (Bruce protocol) treadmill test from May 1988 to January 1991 after myocardial infarction (at least 1 year). Clinical and exercise data were prospectively entered in a computerized database and retrospectively two different groups were selected: (1) 228 patients with exercise-induced ventricular arrhythmias; (2) 549 patients without. Incidence and morphology of exercise-induced ventricular arrhythmias, various exercise parameters and a follow-up were evaluated. Results: Patients with exercise-induced ventricular arrhythmias were older ( P < 0.001), had higher blood pressure ( P < 0.03) and peak exercise rate pressure product ( P < 0.00) than the others. No difference was found in the incidence of exercise-ischaemia: either symptomatic or not. When simple (≤2 Lown) versus complex (≥3 Lown) exercise-induced ventricular arrhythmias were considered, the latter were more frequent in patients with anterior myocardial infarction, shorter exercise duration ( P < 0.001) and lower exercise rate pressure product, lower ejection fraction and lower incidence of exercise-induced ischaemia. In the follow-up (mean 24 ± 13 month) there were 24 deaths: five (2.2%) in patients with exercise-induced ventricular arrhythmias and 19 (3.4%) in patients without. Cardiac event rate was similar in both groups. Conclusions: We conclude that in out-patients with healed myocardial infarction exercise-induced ventricular arrhythmias are quite frequent, but they are not associated with exercise-induced ischaemia, either symptomatic or not. Exercise-induced ventricular arrhythmias seem to be related to age or peak workload. Moreover patients with these arrhythmias have no adjunctive negative risk on prognosis.

Reduction of exercise-induced ventricular arrhythmias in mild symptomatic heart failure by benazepril

We studied 14 patients who had exercise-induced ventricular arrhythmias after a previous Q-wave myocardial infarction. All had symptomatic mild heart failure in New York Heart Association class II and a maximal oxygen consumption between 16 and 20 ml/kg/min. They were treated with the angiotensin converting enzyme inhibitor benazepril (20 mg) and hydrochlorothiazide (50 mg) for 3 months in a double-blind randomized cross-over study. Benazepril improved the maximal oxygen uptake by 15% and exercise time by 18%. Hydrochlorothiazide slightly increased exercise time (5%) and the respiratory exchange ratio but not oxygen consumption. The arrhythmias were nonsustained and reproducible in two baseline recordings. Compared with baseline, benazepril reduced the mean number (3.5 ± 2.5) (± SD) of episodes of ventricular tachycardia by 66%, and total (47.4 ± 40.9) and paired (5.2 ± 4.5) premature ventricular contractions by 61% and 62%, respectively. Hydrochlorothiazide did not reduce the number of arrhythmias. Thus an improved cardiac function induced by benazepril is associated with a reduction in exercise-induced ventricular arrhythmias in patients with symptomatic mild heart failure after infarction.

Plasma catecholamine responses to dynamic exercise in patients with coronary artery disease--the relationship between sympathetic activity and systolic blood pressure and exercise-induced ventricular arrhythmias.

In order to investigate the relationship between sympathetic activity and postexercise systolic blood pressure (SBP) and exercise-induced ventricular arrhythmias in patients with coronary artery disease (CAD), we studied 38 patients and 9 normal subjects who underwent treadmill testing. Peak pressure-rate product was similar in the 2 groups. The plasma concentrations of norepinephrine and epinephrine at rest and immediately after exercise were significantly higher in patients with CAD compared with normal subjects (norepinephrine at rest, p < 0.01; norepinephrine immediately after exercise, p < 0.05; epinephrine at rest, p < 0.05; epinephrine immediately after exercise, p < 0.05). The level of norepinephrine immediately after exercise was significantly higher in 15 patients with a postexercise SBP increase than in 23 patients without that SBP change (p < 0.05), whereas the level of epinephrine was similar in the 2 groups. The level of epinephrine immediately after exercise was significantly higher in 10 patients with exercise-induced premature ventricular contractions than in 28 patients without those arrhythmias (p < 0.05), whereas the level of norepinephrine was similar in the 2 groups. We conclude that a postexercise SBP increase is related to the augmentation of sympathoneural activity and that exercise-induced ventricular arrhythmias are related to the augmentation of sympathoadrenal activity.

Effects of Low-Level Carbon Monoxide Exposure on Resting and Exercise-Induced Ventricular Arrhythmias in Patients with Coronary Artery Disease and No Baseline Ectopy

The effects of acute elevation of carboxyhemoglobin (COHb) concentrations on resting and exercise-induced ventricular arrhythmias were evaluated in 10 patients who had ischemic heart disease and in whom no ectopy during baseline monitoring was noted. After an initial training session, patients were exposed to air, 100 ppm carbon monoxide (CO), or 200 ppm CO on successive days in a randomized, double-blind, cross-over fashion. After exposure to 100 and 200 ppm CO, venous COHb levels averaged 4% and 6%, respectively. Symptom-limited supine exercise was performed after exposure. Eight of the 10 patients had evidence of exercise-induced ischemia--either angina, 1.0 mm ST depression, or abnormal ejection fraction response--during 1 or more exposure days. Ambulatory electrocardiograms were obtained on each day and analyzed for arrhythmia frequency and severity. On air and CO exposure days, each patient had only 0-1 ventricular premature beat/h in the 2 h prior to exposure, during the exposure period, during the subsequent exercise test, and in the 5 h following exercise. In conclusion, low-level CO exposure is not arrhythmogenic in patients with coronary artery disease and no ventricular ectopy at baseline.

Prophylaxis of exercise-induced ventricular arrhythmias by verapamil.

In this study prophylactic antiarrhythmic effects of verapamil on exercise-induced ventricular arrhythmias are evaluated. Investigations were carried out on a total of 22 patients. All patients showed frequent and/or complex ventricular arrhythmias during repeated exercise tests under control conditions. After two control exercise tests all patients were treated with verapamil 120 mg given every 8 hours orally over 4 days. On the 3rd and 4th day of treatment the exercise tests were repeated. Verapamil caused a significant reduction in the incidence and severity of exercise-induced ventricular arrhythmias in 13 out of 22 patients. In patients with exercise-induced ST-segment depression a prophylactic action could be demonstrated in 9 out of 10 cases. The antiarrhythmic effect was independent of changes in heart rate. A reduction in myocardial oxygen consumption and direct electrophysiological effects (suppression of the 'slow response' and/or an increase in the resting potential of the 'depressed fast response') can be considered, as well as a suppression of 'triggered activity' or a direct inhibition of adrenergic effects. Calcium antagonists (type verapamil) prove to be suitable drugs for the treatment of exercise-induced ventricular arrhythmias in patients with myocardial ischaemia.

Exercise induced ventricular arrhythmias. Angiographic correlation with the severity of coronary artery disease.

We correlated the incidence and degree of exercise induced ventricular arrhythmias (EIVA) with the angiographic severity of coronary artery disease (CAD) in 162 patients with a history of stable effort angina, all showing a positive exercise stress test for myocardial ischemia and a greater than or equal to 70% stenosis of a major coronary artery. Patients were grouped according to the following criteria: presence of electrocardiographic evidence of old transmural myocardial infarction (MI), number of significant coronary stenoses and number of left ventricular (LV) areas showing abnormal segmental wall motion (ASWM). The incidence of EIVA in patients with multivessel CAD was higher than in patients with single vessel CAD, but this difference was not statistically significant. The number of LV areas with ASWM was better correlated with the frequency of EIVA, which was 20.0% in patients with normal LV wall motion, 31.2% in patients with 1 area of ASWM, 54.0% in patients with 2 areas of ASWM (p less than 0.005 vs normal LV wall motion), 74.1% in patients with 3 or more areas of ASWM (p less than 0.001 vs normal LV wall motion and 1 area of ASWM), and 81.8% in patients with LV aneurysm (p less than 0.001 vs normal LV wall motion and 1 area of ASWM, p less than 0.005 vs 2 areas of ASWM). Patients with old MI showed a significantly higher incidence of EIVA than those without MI (p less than 0.001), but this difference was due to the more severe LV asynergy in the MI group. In conclusion, our results show that, in a selected population of patients with CAD, the incidence of EIVA correlates better with the extent of LV segmental wall motion abnormalities than with the number of diseased coronary arteries or the presence of an old transmural MI.

Comparative study of exercise-induced ventricular arrhythmias in normal subjects and patients with documented coronary artery disease

The incidence, types and patterns of emergence of treadmill exercise-induced ventricular arrhythmias were studied in 482 subjects with and without coronary heart disease. All subjects were free of premature ventricular complexes at rest and were classified into groups on the basis of their clinical status. In Group IA were 141 patients with chest pain and normal coronary arteriograms and in Group IB 144 age-matched subjects free of clinical evidence of heart disease. Group II consisted of 197 patients with chest pain and arteriographically documented coronary artery disease. Patients in Group IA and II exercised to at least 85 percent of their predicted maximal heart rate or until chest pain occurred. Subjects in Group IB underwent maximal exercise testing. The total incidence of exercise-induced ventricular arrhythmias was 16 percent in Group IA, 44 percent in Group IB and 29 percent in Group II. However, when exercise heart rate at the time of appearance of ventricular arrhythmias was taken into account the incidence of exercise-induced ventricular arrhythmias up to a heart rate of 130/min was 27 percent in the patients with documented coronary artery disease (Group II) compared with rates of 9 and 6 percent, respectively, for Groups IA and IB ( P < 0.001). The incidence rates of multifocal ventricular premature complexes, ventricular tachycardia and ventricular premature complexes at a rate of more than 10/min were also significantly greater at submaximal heart rates in the patients with coronary disease. Patients with three vessel coronary artery disease and abnormal left ventricular wall motion had a significantly greater incidence of exercise-induced ventricular arrhythmias. The incidence of exercise-induced ventricular arrhythmias in patients with coronary disease and a positive S-T segment response was not significantly increased.

Exercise-induced ventricular arrhythmias in patients with coronary artery disease: Their relation to angiographic findings

Ventricular extrasystoles occurring before, during or after graded exercise testing were related to extent of coronary artery disease and to ventricular motion disorders in 81 symptomatic patients undergoing selective coronary and left ventricular angiography; the results were compared with data in 89 similar age-matched patients without arrhythmias. Compared with arrhythmia-free patients, 67 patients with exercise-induced arrhythmias had a significantly greater incidence of prior myocardial infarction, double or triple vessel disease and overall abnormal ventricular contractile patterns. Exercise induced extrasystoles occurred in only 11 percent of patients with insignificant coronary disease. Abolition of resting extrasystoles by exercise was not associated with less extensive coronary disease. Our study suggests that exercise-precipitated arrhythmias may represent a form of subclinical ischemia, signify more advanced degrees of coronary and left ventricular disease, and serve as an aid in detecting potentially high-risk patients.