cardiovascular-agents and Tachycardia--Ventricular

Recurrent ventricular arrhythmias (VA) are a source of significant morbidity in patients without structural heart disease (SHD) and also mortality in patients with SHD. The treatment goals for these two patient populations differ greatly. Areas covered: The secondary prevention of recurrent VA in patients without and with SHD will be reviewed, focusing on clinical data (especially randomized, controlled trials) in the literature as determined through searches in PubMed and ClinicalTrials.gov. This will include β blockers, non-dihydropyridine calcium channel blockers and antiarrhythmic drugs in both subgroups and non-antiarrhythmic medications in SHD. Expert commentary: The available options for medical therapy for VA in both normal hearts and SHD are insufficient, due to substandard efficacy and toxicities. While non-pharmacologic therapies may provide an excellent option, further drug development and randomized trials are needed, as is a reappraisal of the current mode of utilization.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Calcium Channel Blockers; Cardiovascular Agents; Catheter Ablation; Heart Diseases; Humans; Randomized Controlled Trials as Topic; Recurrence; Tachycardia, Ventricular; Ventricular Fibrillation; Ventricular Premature Complexes

Despite improvements in the therapy of underlying heart disease, sudden cardiac death is a major cause of death worldwide. Disturbed Na and Ca handling is known to be a major predisposing factor for life-threatening tachyarrhythmias. In cardiomyocytes, many ion channels and transporters, including voltage-gated Na and Ca channels, cardiac ryanodine receptors, Na/Ca-exchanger, and SR Ca-ATPase are involved in this regulation. We have learned a lot about the pathophysiological relevance of disturbed ion channel function from monogenetic disorders. Changes in the gating of a single ion channel and the activity of an ion pump suffice to dramatically increase the propensity for arrhythmias even in structurally normal hearts. Nevertheless, patients with heart failure with acquired dysfunction in many ion channels and transporters exhibit profound dysregulation of Na and Ca handling and Ca/calmodulin-dependent protein kinase and are especially prone to arrhythmias. A deeper understanding of the underlying arrhythmic principles is mandatory if we are to improve their outcome. This review addresses basic tachyarrhythmic mechanisms, the underlying ionic mechanisms and the consequences for ion homeostasis, and the situation in complex diseases like heart failure.

Topics: Action Potentials; Calcium; Calcium Channels; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cardiovascular Agents; Death, Sudden, Cardiac; Electrocardiography; Epigenesis, Genetic; Excitation Contraction Coupling; Heart Conduction System; Homeostasis; Humans; Ion Channel Gating; Myocytes, Cardiac; Sodium; Sodium Channels; Tachycardia; Tachycardia, Ventricular

Sudden cardiac death is a common cause of death in patients with structural heart disease, genetic mutations, or acquired disorders affecting cardiac ion channels. A wide range of platforms exist to model and study disorders associated with sudden cardiac death. Human clinical studies are cumbersome and are thwarted by the extent of investigation that can be performed on human subjects. Animal models are limited by their degree of homology to human cardiac electrophysiology, including ion channel expression. Most commonly used cellular models are cellular transfection models, which are able to mimic the expression of a single-ion channel offering incomplete insight into changes of the action potential profile. Induced pluripotent stem cell-derived cardiomyocytes resemble, but are not identical, adult human cardiomyocytes and provide a new platform for studying arrhythmic disorders leading to sudden cardiac death. A variety of platforms exist to phenotype cellular models, including conventional and automated patch clamp, multielectrode array, and computational modeling. Induced pluripotent stem cell-derived cardiomyocytes have been used to study long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy, and other hereditary cardiac disorders. Although induced pluripotent stem cell-derived cardiomyocytes are distinct from adult cardiomyocytes, they provide a robust platform to advance the science and clinical care of sudden cardiac death.

Topics: Animals; Cardiovascular Agents; Cell Differentiation; Cells, Cultured; Clinical Trials as Topic; Computer Simulation; Death, Sudden, Cardiac; Disease Models, Animal; Drug Evaluation, Preclinical; Electrophysiology; Forecasting; Heart Diseases; Humans; Induced Pluripotent Stem Cells; Ion Channels; Long QT Syndrome; Models, Cardiovascular; Myocytes, Cardiac; Organ Culture Techniques; Patch-Clamp Techniques; Tachycardia, Ventricular

We review the pharmacologic, interventional and device programming treatment options for patients with implantable cardioverter-defibrillators who present with acute heart failure and implantable cardioverter-defibrillator shocks.

Topics: Acute Disease; Cardiovascular Agents; Catheter Ablation; Clinical Trials as Topic; Defibrillators, Implantable; Electric Countershock; Electrocardiography; Equipment Failure Analysis; Heart Failure; Humans; Intra-Aortic Balloon Pumping; Patient Selection; Severity of Illness Index; Sympathetic Nervous System; Tachycardia, Ventricular

According to the American Heart Association it is estimated that the United States will spend close to $39 billion in 2010 to treat over five million Americans suffering from heart failure. Patients with heart failure suffer from dyspnea and decreased exercised tolerance and are at increased risk for fatal ventricular arrhythmias. Food and Drug Administration -approved pharmacologic therapies for heart failure include diuretics, inhibitors of the renin-angiotensin system, and β-adrenergic receptor antagonists. Over the past 20 years advances in the field of ryanodine receptor (RyR2)/calcium release channel research have greatly advanced our understanding of cardiac physiology and the pathogenesis of heart failure and arrhythmias. Here we review the key observations, controversies, and discoveries that have led to the development of novel compounds targeting the RyR2/calcium release channel for treating heart failure and for preventing lethal arrhythmias.

Topics: Animals; Atrial Fibrillation; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cardiovascular Agents; Cyclic AMP-Dependent Protein Kinases; Drug Design; Heart Conduction System; Heart Failure; Humans; Infant, Newborn; Myocardial Contraction; Phosphorylation; Receptors, Adrenergic, beta; Ryanodine Receptor Calcium Release Channel; Sudden Infant Death; Tachycardia, Ventricular; Tacrolimus Binding Proteins

Underlying causes of ventricular tachycardia (VT) or complex ventricular arrhythmias (VA) should be treated if possible. This may include beta-adrenergic blockade radiofrequency catheter ablation and automatic implantable cardioverter-defibrillators. The ACC/AHA Class I indications for an AICD are discussed. Patients with AICDs should be treated with biventricular pacing, not with dual-chamber rate-responsive pacing at a rate of 70/minute.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Calcium Channel Blockers; Cardiovascular Agents; Catheter Ablation; Defibrillators, Implantable; Humans; Tachycardia, Ventricular; Ventricular Fibrillation

A cardiac localization is one of the most severe manifestations of sarcoidosis and may cause sudden death (ventricular tachycardia or atrial ventricular block III) or restrictive cardiomyopathy. Lesions are most frequently observed in the interventricular septum and the free left wall. Granulomatous infiltation can provoke nonspecific clinical, electric and echocardiographic signs, which, associated with regressive dipyridamol uptake on tomoscintigraphy, are suggestive of cardiac sarcoidosis. The diagnosis of cardiac sarcoidosis is based on the presence of systemic sarcoidosis, histological evidence of granuloma and the lack of another cause of cardiomyopathy. Corticosteroid therapy is indicated, associated with specific cardiologic treatments.

Topics: Anti-Inflammatory Agents; Biopsy; Cardiomyopathies; Cardiomyopathy, Restrictive; Cardiovascular Agents; Death, Sudden, Cardiac; Dipyridamole; Echocardiography; Electrocardiography; Heart Block; Humans; Immunosuppressive Agents; Magnetic Resonance Imaging; Sarcoidosis; Steroids; Tachycardia, Ventricular; Vasodilator Agents

To review evaluation and treatment of patients with ventricular arrhythmias, based on recent studies, with an emphasis on randomized controlled trials.. MEDLINE search of English-language publications of ventricular arrhythmias and their references from 1966 through April 27, 1998. References to articles were also scanned to broaden the search.. Randomized controlled trials and all large nonrandomized trials of arrhythmias and arrhythmia therapy were reviewed. In addition, studies that led to changes in approach to patients with arrhythmias were reviewed.. We reviewed articles jointly for pertinent studies and information.. The goals of treatment of the patient with ventricular arrhythmias are to suppress symptoms and prevent a fatal event. The steps in providing such therapy include defining the cardiac anatomy, assessing arrhythmia risk through noninvasive or invasive testing, and prescribing treatment based on these results. Patients may be separated into high- and low-risk groups to help identify appropriate treatment. While low-risk groups may benefit from reassurance or medications such as beta-blockers or verapamil, high-risk groups have been more difficult to treat. Recent randomized trials of implantable cardioverter defibrillators for ventricular arrhythmias suggest that they may provide better protection for high-risk patients than do antiarrhythmic medications.. Treatment and understanding of risk from ventricular arrhythmias have advanced substantially in recent years. Classifying patients as being at high or low risk for fatal arrhythmias allows the physician to identify appropriate treatments for the high-risk patient without exposing the low-risk patient to unnecessary treatment-related risks.

Topics: Algorithms; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiac Surgical Procedures; Cardiovascular Agents; Catheter Ablation; Clinical Trials as Topic; Defibrillators, Implantable; Electrocardiography; Electrophysiology; Humans; Lidocaine; Risk Assessment; Survival Analysis; Tachycardia, Ventricular; Ventricular Dysfunction, Left; Ventricular Fibrillation

Chronic heart failure (CHF) is generally associated with a poor prognosis with an annual mortality rate ranging between 15-50% depending on the severity of cardiac dysfunction thus presenting a major health problem in our society. Drugs for the treatment of CHF include vasodilators (ACE-inhibitors, angiotensin II receptor blockers), diuretics, digoxin and beta-blockers. However, antiarrhythmic drugs are not currently recommended in the management of CHF with the exception of beta-blockers for which a favorable effect on the prognosis could be shown. Amiodarone is effective in the suppression of ventricular arrhythmias without a significant effect on total mortality. Implanted defibrillators are superior to antiarrhythmic drug therapy in prolonging survival among survivors of sudden cardiac death. They should be offered as firstline therapy in case of life-threatening ventricular tachy-arrhythmias.

Topics: Anti-Arrhythmia Agents; Cardiovascular Agents; Chronic Disease; Death, Sudden, Cardiac; Drug Therapy, Combination; Follow-Up Studies; Heart Failure; Humans; Survival Rate; Tachycardia, Ventricular

Ventricular arrhythmias are a frequent finding in patients with heart failure, and heart failure is a major underlying condition which is correlated to sudden death. Therefore, both sudden death and death from progression of heart failure strongly overlap. Besides long-term ECG recording, newer diagnostic techniques have been developed. The prognostic significance of the signal-averaged ECG in patients with advanced left ventricular dysfunction in the presence of coronary artery disease has been demonstrated; however, in patients with dilated cardiomyopathy, signal-averaging for detection of late potentials has not yet been clearly established as a useful diagnostic tool. Furthermore, heart period variability has been shown to correlate to overall mortality but not to a specific mechanism. Finally, programmed ventricular stimulation, though useful in patients with left ventricular dysfunction and/or heart failure in the setting of coronary artery disease, is of questionable significance in patients with dilated cardiomyopathy. With increasing degrees of left ventricular dysfunction, the efficacy of antiarrhythmic drugs decreases. On the other hand, with increasing degrees of heart failure, antiarrhythmic drugs demonstrate a greater negative inotropic effect, more frequent proarrhythmic effects, and more frequent bradyarrhythmias. Currently, several ongoing amiodarone trials are assessing different approaches of antiarrhythmic treatment in patients with heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Cardiovascular Agents; Clinical Trials as Topic; Death, Sudden, Cardiac; Defibrillators, Implantable; Electrocardiography; Heart Failure; Humans; Risk Factors; Tachycardia, Ventricular

To test the hypothesis that female prevalence is greater than expected among reported cases of torsades de pointes associated with cardiovascular drugs that prolong cardiac repolarization.. A MEDLINE search of the English-language literature for the period of 1980 through 1992, using the terms torsade de pointes, polymorphic ventricular tachycardia, atypical ventricular tachycardia, proarrhythmia, and drug-induced ventricular tachycardia, supplemented by pertinent references (dating back to 1964) from the reviewed articles and by personal communications with researchers involved in this field.. Ninety-three articles were identified describing at least one case of polymorphic ventricular tachycardia (with gender specified) associated with quinidine, procainamide hydrochloride, disopyramide, amiodarone, sotalol hydrochloride, bepridil hydrochloride, or prenylamine. A total of 332 patients were included in the analysis following application of prospectively defined criteria (eg, corrected QT [QTc] interval of 0.45 second or greater while receiving drug).. Clinical and electrocardiographic descriptors were extracted for analysis. Expected female prevalence for torsades de pointes associated with quinidine, procainamide, disopyramide, and aminodarone was conservatively estimated from gender-specific data reported for antiarrhythmic drug prescriptions in 1986, as derived from the National Disease and Therapeutic Index, a large pharmaceutical database; expected female prevalence for torsades de pointes associated with sotalol, bepridil, and prenylamine was assumed to be 50% or less since these agents are prescribed for male-predominant cardiovascular conditions.. Women made up 70% (95% confidence interval, 64% to 75%) of the 332 reported cases of cardiovascular-drug-related torsades de pointes, and a female prevalence exceeding 50% was observed in 20 (83%) of 24 studies having at least four included cases. When analyzed according to various descriptors, women still constituted the majority (range, 51% to 94% of torsades de pointes cases), irrespective of the presence or absence of underlying coronary artery or rheumatic heart disease, left ventricular dysfunction, type of underlying arrhythmia, hypokalemia, hypomagnesemia, bradycardia, concomitant digoxin treatment, or level of QTc at baseline or while receiving drug. When cases of torsades de pointes were analyzed by individual drug, observed female prevalence was always greater than expected, representing a statistically significant difference (P < .05) for all agents except procainamide.. These findings strongly suggest that women are more prone than men to develop torsades de pointes during administration of cardiovascular drugs that prolong cardiac repolarization. The pathophysiological basis for, and therapeutic implications of, this gender disparity should be further investigated.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amiodarone; Bepridil; Cardiovascular Agents; Disopyramide; Female; Humans; Male; Middle Aged; Prenylamine; Procainamide; Quinidine; Risk Factors; Sex; Sotalol; Syncope; Tachycardia, Ventricular; Torsades de Pointes

The role of implantable cardioverter-defibrillator (ICD) placement in the primary prevention of sudden cardiac death (SCD) in all consecutive patients with left ventricular ejection fraction (LVEF) ≤ 35% is still a matter of hot debate due to the fact that the population of these patients is highly heterogeneous in terms of the SCD risk. Nevertheless, reduced LVEF is still the only established criterion during qualification of patients for ICD implantation in the primary prevention of SCD, therefore identification of persons with particularly high risk among patients with LVEF ≤35% is currently of lesser importance. More important seems to be the selection of individuals with relatively low risk of SCD in whom ICD implantation can be safely postponed. The aim of the study was to determine whether well-known, non-invasive parameters, such as microvolt T-wave alternans (MTWA), baroreflex sensitivity (BRS) and short-term heart rate variability (HRV), can be helpful in the identification of low-arrhythmic risk patients with ischemic left ventricular systolic dysfunction.. In 141 patients with coronary artery disease and LVEF ≤ 35%, MTWA testing, as well as BRS and short-term HRV parameters, were analysed. During 34 ± 13 months of follow-up 37 patients had arrhythmic episode (EVENT): SCD, non-fatal sustained ventricular arrhythmia (ventricular tachycardia [VT] or ventricular fibrillation [VF]), or adequate high-voltage ICD intervention (shock) due to a rapid ventricular arrhythmia ≥200/min. LVEF, non-negative MTWA (MTWA_non-neg), BRS and low frequency power in normalized units (LFnu) turned out to be associated with the incidence of EVENT in univariate Cox analysis. The cut-off values for BRS and LFnu that most accurately distinguished between patients with and without EVENT were 3 ms/mmHg and 23, respectively. The only variable that provided 100% negative predictive value (NPV) for EVENT was negative MTWA result (MTWA_neg), but solely for initial 12 months of the follow-up; the NPVs for other potential predictors of the EVENT were lower. The cut-off values for BRS and LFnu that provide 100% NPV for EVENT during 12 and 24 months were higher: 6.0 ms/mmHg and 73 respectively, but the gain in the NPV occurred at an expense of the number of identified patients. However, the number of identified non-risk patients turned out to be higher when the predictive model included MTWA_neg and the lower cut-off values for ANS parameters: 100% NPV for 12 and 24 months of follow-up was obtained for combination MTWA_neg and BRS ≥ 3 ms/mmHg, for combination MTWA_neg and LFnu ≥ 23 100% NPV was obtained for 12 months.. Well-known, non-invasive parameters, such as MTWA, BRS and short-term HRV indices may be helpful in the identification of individuals with a relatively low risk of malignant ventricular arrhythmias among patients with ischemic left ventricular systolic dysfunction; in such persons, implantation of ICD could be safely postponed.

Topics: Aged; Baroreflex; Cardiovascular Agents; Death, Sudden, Cardiac; Defibrillators, Implantable; Electrocardiography; Female; Follow-Up Studies; Heart Rate; Humans; Male; Middle Aged; Myocardial Ischemia; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prospective Studies; Reflex, Abnormal; Risk Assessment; Systole; Tachycardia, Ventricular; Ventricular Dysfunction, Left; Ventricular Fibrillation

Ventricular tachycardia (VT) and ventricular fibrillation (VF) remain a challenging problem in patients with implantable cardioverter-defibrillators (ICDs).. This study aimed to determine whether ranolazine administration decreases the likelihood of VT, VF, or death in patients with an ICD.. This was double-blind, placebo-controlled clinical trial in which high-risk ICD patients with ischemic or nonischemic cardiomyopathy were randomized to 1,000 mg ranolazine twice a day or placebo. The primary endpoint was VT or VF requiring appropriate ICD therapy or death, whichever occurred first. Pre-specified secondary endpoints included ICD shock for VT, VF, or death and recurrent VT or VF requiring ICD therapy.. Among 1,012 ICD patients (510 randomized to ranolazine and 502 to placebo) the mean age was 64 ± 10 years and 18% were women. During 28 ± 16 months of follow-up there were 372 (37%) patients with primary endpoint, 270 (27%) patients with VT or VF, and 148 (15%) deaths. The blinded study drug was discontinued in 199 (39.6%) patients receiving placebo and in 253 (49.6%) patients receiving ranolazine (p = 0.001). The hazard ratio for ranolazine versus placebo was 0.84 (95% confidence interval: 0.67 to 1.05; p = 0.117) for VT, VF, or death. In a pre-specified secondary analysis, patients randomized to ranolazine had a marginally significant lower risk of ICD therapies for recurrent VT or VF (hazard ratio: 0.70; 95% confidence interval: 0.51 to 0.96; p = 0.028). There were no other significant treatment effects in other pre-specified secondary analyses, which included individual components of the primary endpoint, inappropriate shocks, cardiac hospitalizations, and quality of life.. In high-risk ICD patients, treatment with ranolazine did not significantly reduce the incidence of the first VT or VF, or death. However, the study was underpowered to detect a difference in the primary endpoint. In prespecified secondary endpoint analyses, ranolazine administration was associated with a significant reduction in recurrent VT or VF requiring ICD therapy without evidence for increased mortality. (Ranolazine Implantable Cardioverter-Defibrillator Trial [RAID]; NCT01215253).

Topics: Aged; Cardiovascular Agents; Defibrillators, Implantable; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Ranolazine; Risk Factors; Tachycardia, Ventricular; Ventricular Fibrillation

Appropriate implantable cardioverter-defibrillator (ICD) therapy for ventricular tachycardia (VT) or ventricular fibrillation (VF) depends, in part, on the programming of tachycardia zones.. We assessed events treated with ICD shocks or antitachycardia pacing (ATP) in the Inhibition of Unnecessary RV Pacing with AV Search Hysteresis in ICDs (INTRINSIC RV) trial.. ATP and shock episodes from 1530 patients with dual-chamber ICDs were analyzed.. For episodes in which electrograms were stored and adjudicated, ATP was delivered for 763 episodes (182 patients), shock-only was delivered for 300 episodes (146 patients), and shock following ATP was delivered for 81 episodes (56 patients). ATP was delivered appropriately for 507 episodes (130 patients), with 93% success, and inappropriately for 256 episodes (89 patients). For ATP episodes, appropriate (VT: 170 ± 28 bpm) and inappropriate (not VT: 165 ± 21 bpm) rates did not differ (P = .16). When the initial therapy was shock, onset rates were higher for appropriate therapy than for inappropriate therapy (224 ± 46 bpm vs 187 ± 31 bpm; P <.001). Inappropriate ATP was more likely to be followed by a shock (odds ratio 2.49; 95% confidence interval 1.56-3.97; P <.001). Fifty-eight percent (225 of 381) of shocked episodes had rates <200 bpm. For episodes between 200 and 250 bpm, 20% (23 of 113) were polymorphic VT or VF, 59% were monomorphic VT, 19% were supraventricular, and <1% was artifact. For episodes >250 bpm, 37% were VF, 28% polymorphic VT, 23% monomorphic VT, 7% supraventricular, and 5% artifact.. In a general ICD population, ATP treated VT effectively or obviated the need for shock. Most ventricular arrhythmias <250 bpm were not VF. Proper zone programming may identify and treat VT without shock.

Topics: Aged; Cardiac Pacing, Artificial; Cardiovascular Agents; Death, Sudden, Cardiac; Defibrillators, Implantable; Electric Countershock; Electrocardiography; Equipment Failure Analysis; Health Status; Humans; Male; Middle Aged; Monitoring, Physiologic; Outcome and Process Assessment, Health Care; Tachycardia, Ventricular; Treatment Outcome

Ventricular arrhythmias remain a lethal complication of acute coronary syndromes (ACS). However, the incidence and prognosis of sustained ventricular tachycardia/ventricular fibrillation (VT/VF) in contemporary non-ST-segment-elevation (NSTE) ACS populations are not well described.. We examined the incidence of VT/VF and subsequent survival among 9211 patients enrolled in the Early Glycoprotein IIb/IIIa Inhibition in NSTE ACS (EARLY ACS) trial. The cumulative incidence of VT/VF was 1.5% (n=141); 0.6% (n=55) had VT/VF ≤48 hours after enrollment, and 0.9% (n=86) had VT/VF >48 hours after enrollment. Patients with VT/VF more frequently had prior heart failure, an ejection fraction <30%, and triple-vessel coronary artery disease. Predictors of sustained VT/VF were similar regardless of the timing of VT/VF (≤48 versus >48 hours). Patients with VT/VF ≤48 hours after enrollment had higher 30-day mortality than those who did not have VT/VF ≤48 hours (13.0% versus 2.2%; adjusted odds ratio, 6.73; 95% confidence interval, 2.68-16.9). The increased risk of death associated with VT/VF ≤48 hours persisted at 1 year. The risk of mortality, relative to patients without VT/VF, was greater for patients with VT/VF >48 hours (hazard ratio, 20.70; 95% confidence interval, 15.39-27.85) than for those with earlier VT/VF (hazard ratio, 7.45; 95% confidence interval, 4.60-12.08; P=0.0003). The frequency of arrhythmic death was higher in patients with VT/VF than in those without VT/VF (26.4% versus 6.9%).. Sustained VT/VF is infrequent after NSTE ACS but is as likely to occur after 48 hours as within the first 48 hours. The marked increase in all-cause death among NSTE ACS patients with both early and late sustained VT/VF raises important considerations for aggressive monitoring beyond 48 hours and interventions to prevent arrhythmic death in these patients.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00089895.

Topics: Acute Coronary Syndrome; Aged; Cardiovascular Agents; Cohort Studies; Double-Blind Method; Female; Humans; Male; Middle Aged; Platelet Glycoprotein GPIIb-IIIa Complex; Tachycardia, Ventricular; Ventricular Fibrillation

The effects of cardiac resynchronization therapy (CRT) in patients with mildly symptomatic heart failure have not been fully elucidated.. The Multicenter InSync ICD Randomized Clinical Evaluation II (MIRACLE ICD II) was a randomized, double-blind, parallel-controlled clinical trial of CRT in NYHA class II heart failure patients on optimal medical therapy with a left ventricular (LV) ejection fraction < or =35%, a QRS > or =130 ms, and a class I indication for an ICD. One hundred eighty-six patients were randomized: 101 to the control group (ICD activated, CRT off) and 85 to the CRT group (ICD activated, CRT on). End points included peak VO2, VE/CO2, NYHA class, quality of life, 6-minute walk distance, LV volumes and ejection fraction, and composite clinical response. Compared with the control group at 6 months, no significant improvement was noted in peak VO2, yet there were significant improvements in ventricular remodeling indexes, specifically LV diastolic and systolic volumes (P=0.04 and P=0.01, respectively), and LV ejection fraction (P=0.02). CRT patients showed statistically significant improvement in VE/CO2 (P=0.01), NYHA class (P=0.05), and clinical composite response (P=0.01). No significant differences were noted in 6-minute walk distance or quality of life scores.. In patients with mild heart failure symptoms on optimal medical therapy with a wide QRS complex and an ICD indication, CRT did not alter exercise capacity but did result in significant improvement in cardiac structure and function and composite clinical response over 6 months.

Topics: Aged; Cardiovascular Agents; Defibrillators, Implantable; Disease Progression; Double-Blind Method; Electric Countershock; Electrocardiography; Exercise Test; Exercise Tolerance; Heart Conduction System; Heart Failure; Humans; Male; Middle Aged; Postoperative Complications; Survival Rate; Tachycardia, Ventricular; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Fibrillation; Ventricular Remodeling

Implantable cardioverter defibrillator (ICD) therapy with backup ventricular pacing increases survival in patients with life-threatening ventricular arrhythmias. Most currently implanted ICD devices provide dual-chamber pacing therapy. The most common comorbid cause for mortality in this population is congestive heart failure.. To determine the efficacy of dual-chamber pacing compared with backup ventricular pacing in patients with standard indications for ICD implantation but without indications for antibradycardia pacing.. The Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial, a single-blind, parallel-group, randomized clinical trial.. A total of 506 patients with indications for ICD therapy were enrolled between October 2000 and September 2002 at 37 US centers. All patients had a left ventricular ejection fraction (LVEF) of 40% or less, no indication for antibradycardia pacemaker therapy, and no persistent atrial arrhythmias.. All patients had an ICD with dual-chamber, rate-responsive pacing capability implanted. Patients were randomly assigned to have the ICDs programmed to ventricular backup pacing at 40/min (VVI-40; n = 256) or dual-chamber rate-responsive pacing at 70/min (DDDR-70; n = 250). Maximal tolerated medical therapy for left ventricular dysfunction, including angiotensin-converting enzyme inhibitors and beta-blockers, was prescribed to all patients.. Composite end point of time to death or first hospitalization for congestive heart failure.. One-year survival free of the composite end point was 83.9% for patients treated with VVI-40 compared with 73.3% for patients treated with DDDR-70 (relative hazard, 1.61; 95% confidence interval [CI], 1.06-2.44). The components of the composite end point, mortality of 6.5% for VVI-40 vs 10.1% for DDDR-70 (relative hazard, 1.61; 95% CI, 0.84-3.09) and hospitalization for congestive heart failure of 13.3% for VVI-40 vs 22.6% for DDDR-70 (relative hazard, 1.54; 95% CI, 0.97-2.46), also trended in favor of VVI-40 programming.. For patients with standard indications for ICD therapy, no indication for cardiac pacing, and an LVEF of 40% or less, dual-chamber pacing offers no clinical advantage over ventricular backup pacing and may be detrimental by increasing the combined end point of death or hospitalization for heart failure.

Topics: Adrenergic beta-Antagonists; Aged; Amiodarone; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Anticoagulants; Arrhythmias, Cardiac; Cardiac Pacing, Artificial; Cardiovascular Agents; Catheter Ablation; Defibrillators, Implantable; Digoxin; Diuretics; Female; Heart Failure; Humans; Male; Middle Aged; Pacemaker, Artificial; Single-Blind Method; Survival Analysis; Tachycardia, Ventricular; Ventricular Dysfunction, Left; Warfarin

Topics: Cardiovascular Agents; Defibrillators; Electric Countershock; Female; Grief; Humans; Middle Aged; Recurrence; Tachycardia, Ventricular; Takotsubo Cardiomyopathy; Treatment Outcome; Ventricular Function, Left; Wearable Electronic Devices

Topics: Aneurysm, False; Bisoprolol; Cardiovascular Agents; Catheter Ablation; Female; Heart Ventricles; Humans; Middle Aged; Tachycardia, Ventricular; Ventricular Dysfunction, Left

Topics: Adult; Aged; California; Cardiovascular Agents; Clinical Decision-Making; Coronary Vessel Anomalies; Defibrillators, Implantable; Electric Countershock; Female; Humans; Incidence; Male; Middle Aged; Percutaneous Coronary Intervention; Recurrence; Retrospective Studies; Risk Factors; ST Elevation Myocardial Infarction; Tachycardia, Ventricular; Time Factors; Treatment Outcome; Vascular Diseases; Ventricular Fibrillation

Conventional treatment strategies for catecholaminergic polymorphic ventricular tachycardia (CPVT) include avoidance of strenuous exercise and competitive sports, drugs such as ß-blockers and flecainide and, cervical sympathectomy. An implantable cardioverter-defibrillator (ICD) has been utilized if the response to these strategies is inadequate; however, ICD use in CPVT patients, in addition to usual complications, is associated with an increased risk of life-threatening electrical storm. Ivabradine is a selective inhibitor of hyperpolarization-activated cyclic nucleotide-gated potassium channel 4 generated funny current (I

Topics: Adolescent; Cardiovascular Agents; Electrocardiography; Exercise Test; Flecainide; Humans; Ivabradine; Male; Nadolol; Phenotype; Sympathectomy; Tachycardia, Ventricular

Neuraxial modulation therapies, such as stellate ganglion block, thoracic epidural anaesthesia, and cardiac sympathetic denervation, are effective for ventricular arrhythmias. However, these treatments can increase the risk of bleeding and infection. In this case report, stellate ganglion phototherapy was safely and effectively performed for refractory ventricular tachycardias in a patient with a history of left ventricular assist device implantation. Stellate ganglion phototherapy may have the potential to treat refractory ventricular arrhythmias as an additive therapy or bridge therapy.

Topics: Adult; Anticoagulants; Bundle-Branch Block; Cardiac Resynchronization Therapy; Cardiomyopathy, Dilated; Cardiovascular Agents; Defibrillators, Implantable; Drug Resistance; Electric Countershock; Electrocardiography; Heart Failure; Heart Transplantation; Heart-Assist Devices; Humans; Lasers, Semiconductor; Male; Phototherapy; Preoperative Period; Risk Adjustment; Stellate Ganglion; Tachycardia, Ventricular; Treatment Outcome

Topics: Action Potentials; Animals; Calcium; Calcium-Binding Proteins; Cardiovascular Agents; Diabetes Mellitus, Experimental; Female; Heart Rate; Mice; Myocardial Reperfusion Injury; Ranolazine; Tachycardia, Ventricular

A 47-year-old recreational sportsman showed in a routine ergometry polymorphic ventricular extrasystoles with good physical performance.. In resting ECG impressed ventricular extrasystoles (VES) predominantly right-hand-block-like with superior axis, a long-term ECG yielded up to 100 VES per hour. Echocardiographically imposing 4 - 5 trabeculae, feathered, reticular structures apically in the left and lower in the right ventricle. The cardio-MRT revealed a wall dilation laterally and apically with increased trabecularization, no late enhancement.. mild form of NCCM, currently asymptomatic THERAPY:  Cardiac insufficiency treatment is based on the guidelines, including ICD-CRT therapy. We recommended ramipril and decided against transvenous ICD implantation. At the time of the presentation, subcutaneous ICD systems were not available. Family screening and genotyping of affected persons are recommended.. Most patients have cardiac insufficiency, rhythmic symptoms, or thrombi formation in the noncompact portions of the left ventricular wall. Ventricular tachycardias are frequent and sudden cardiac death is the leading cause of death. Arrythmias are accessible to medication or ablation treatment. Endurance sports lead to favorable adaptations of the cardiovascular system in spite of increased risk of sudden cardiac death. The example shows that asymptomatic boundary findings also exist. Whether a sporting activity has a protective influence must be further investigated.. Ein 47-jähriger Freizeitsportler zeigte in einer Routineergometrie polymorphe ventrikuläre Extrasystolen bei guter körperlicher Leistungsfähigkeit.. Im Ruhe-EKG imponierten ventrikuläre Extrasystolen (VES) überwiegend rechtsschenkelblockartig mit superiorer Achse, ein Langzeit-EKG ergab bis 100 VES pro Stunde. Echokardiografisch imponierten 4 – 5 Trabekel, gefiederte, netzartige Strukturen apikal im linken und geringer im rechten Ventrikel. Das Kardio-MRT ergab eine Wandverdünnung lateral und apikal mit vermehrter Trabekularisierung, kein Late-Enhancement.. milde Form einer NCCM, aktuell asymptomatisch.. Die Herzinsuffizienzbehandlung orientiert sich an den Leitlinien einschließlich ICD-CRT-Therapie. Wir empfahlen Ramipril und entschieden uns gegen eine transvenöse ICD-Implantation. Zum Zeitpunkt der Vorstellung waren subkutane ICD-Systeme noch nicht erhältlich. Ein Familienscreening und eine Genotypisierung Betroffener werden empfohlen.. Die meisten Patienten weisen bei Vorstellung eine Herzinsuffizienz, Rhythmussymptomatik oder Thrombenbildung in den nichtkompakten Anteilen der linksventrikulären Wand auf. Ventrikuläre Tachykardien sind häufig und der plötzliche Herztod die häufigste Todesursache. Arrythmien sind einer medikamentösen oder Ablationsbehandlung zugänglich. Ausdauersport führt zu günstigen Anpassungen des Herz-Kreislaufsystems trotz erhöhtem Risiko für den plötzlichen Herztod. Das Beispiel zeigt, dass auch asymptomatische Grenzbefunde existieren. Ob eine sportliche Betätigung einen protektiven Einfluss hat, muss weiter untersucht werden.

Topics: Cardiovascular Agents; Diagnostic Tests, Routine; Electrocardiography; Humans; Male; Middle Aged; Ramipril; Tachycardia, Ventricular

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal hereditary disease characterized by complex ventricular arrhythmias provoked by exercise or emotional stress and by a high mortality rate in young individuals. Nadolol alone or in combination with flecainide is the most effective therapy. However, compliance to treatment is often low due to side effects. We report two patients with CPVT in whom side effects of treatment prompted discontinuation of flecainide or nadolol and in whom ivabradine was successfully added to therapy. In these two patients, ivabradine in combination with nadolol or flecainide was well tolerated and successfully suppressed nonsustained polymorphic ventricular tachycardia and couplets. Thus, ivabradine could limit the use of implantable cardioverter-defibrillators or left cardiac sympathetic denervation in CPVT patients with uncontrollable ventricular arrhythmias.

Topics: Adolescent; Anti-Arrhythmia Agents; Cardiovascular Agents; Electrocardiography; Exercise Test; Female; Flecainide; Humans; Ivabradine; Male; Nadolol; Tachycardia, Ventricular; Young Adult

Topics: Administration, Oral; Aged, 80 and over; Cardiovascular Agents; Coronary Angiography; Diagnosis, Differential; Digoxin; Electrocardiography; Female; Heart Rate; Humans; Predictive Value of Tests; Tachycardia, Ventricular

Early repolarization syndrome (ERS) is associated with polymorphic ventricular tachycardia (PVT) and ventricular fibrillation, leading to sudden cardiac death.. The present study tests the hypothesis that the transient outward potassium current (Ito)-blocking effect of phosphodiesterase-3 (PDE-3) inhibitors plays a role in reversing repolarization heterogeneities responsible for arrhythmogenesis in experimental models of ERS.. Transmembrane action potentials (APs) were simultaneously recorded from epicardial and endocardial regions of coronary-perfused canine left ventricular (LV) wedge preparations, together with a transmural pseudo-electrocardiogram. The Ito agonist NS5806 (7-15 μM) and L-type calcium current (ICa) blocker verapamil (2-3 μM) were used to induce an early repolarization pattern and PVT.. After stable induction of arrhythmogenesis, the PDE-3 inhibitors cilostazol and milrinone or isoproterenol were added to the coronary perfusate. All were effective in restoring the AP dome in the LV epicardium, thus abolishing the repolarization defects responsible for phase 2 reentry and PVT. Arrhythmic activity was suppressed in 7 of 8 preparations by cilostazol (10 μM), 6 of 7 by milrinone (2.5 μM), and 7 of 8 by isoproterenol (0.1-1 μM). Using voltage clamp techniques applied to LV epicardial myocytes, both cilostazol (10 μM) and milrinone (2.5 μM) were found to reduce Ito by 44.4% and 40.4%, respectively, in addition to their known effects to augment ICa.. Our findings suggest that PDE-3 inhibitors exert an ameliorative effect in the setting of ERS by producing an inward shift in the balance of current during the early phases of the epicardial AP via inhibition of Ito as well as augmentation of ICa, thus reversing the repolarization defects underlying the development of phase 2 reentry and ventricular tachycardia/ventricular fibrillation.

Topics: Action Potentials; Animals; Cardiac Electrophysiology; Cardiovascular Agents; Cilostazol; Death, Sudden, Cardiac; Disease Models, Animal; Dogs; Electrocardiography; Ion Channels; Isoproterenol; Milrinone; Tachycardia, Ventricular; Tetrazoles; Ventricular Fibrillation

Topics: Acute Coronary Syndrome; Aged; Cardiovascular Agents; Catheter Ablation; Combined Modality Therapy; Disease Management; Electric Countershock; Humans; Intra-Aortic Balloon Pumping; Male; Middle Aged; Out-of-Hospital Cardiac Arrest; Purkinje Fibers; Recurrence; Shock, Cardiogenic; Stents; Tachycardia, Ventricular; Ventricular Fibrillation

Topics: Adrenal Cortex Hormones; Biopsy; Cardiomyopathies; Cardiovascular Agents; Catheter Ablation; Combined Modality Therapy; Cyclophosphamide; Defibrillators, Implantable; Electrocardiography; Heart Septum; Humans; Hypertrophy, Right Ventricular; Lymph Nodes; Magnetic Resonance Imaging; Male; Middle Aged; Sarcoidosis; Sarcoidosis, Pulmonary; Syncope; Tachycardia, Ventricular; Ultrasonography

Eicosapentaenoic acid (EPA) has antiarrhythmic effects. The J-wave on an electrocardiogram is associated with a high incidence of ventricular tachycardia/fibrillation (VT/VF). We evaluated relationships between EPA and J-waves, and their involvement in the occurrence of VT/VF in acute myocardial infarction (AMI). Two hundred consecutive patients undergoing successful percutaneous coronary intervention within 12 h after AMI onset were enrolled. Serum EPA level and J-waves at admission were evaluated. The patients were divided into two groups according to the optimal cutoff value (2.94) of serum EPA level (% of total fatty acids): LOW (<2.94, 61 ± 11 years, n = 103) and HIGH groups (≥2.94, 70 ± 13 years, n = 81). J-waves were observed more frequently in the LOW (36/103, 35 %) than in HIGH group (16/81, 20 %) (P = 0.020). The 30-day incidence of VT/VF including those occurring before admission was higher in the LOW (19.5 %) than in HIGH group (6.2 %) (P = 0.009). The patients with J-waves showed a higher incidence of VT/VF (23.1 %) than those without J-waves (9.9 %) (P = 0.019). Kaplan-Meier analysis showed that the highest incidence of VT/VF was observed in the LOW with J-wave group (27.8 %), followed by the LOW without J-wave (15.0 %), HIGH with J-wave (12.5 %), and HIGH without J-wave (4.6 %) (P = 0.013). Cox proportional hazard analysis revealed that Killip grade and low serum EPA level or presence of J-waves were significantly associated with the incidence of VT/VF. Low serum EPA level is a risk for incidence of VT/VF in the acute phase of myocardial infarction. Involvement of the J-wave and its possible link with EPA in the pathogenesis of ischemia-induced VT/VF are suggested.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Eicosapentaenoic Acid; Electrocardiography; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Risk Factors; Tachycardia, Ventricular; Treatment Outcome; Ventricular Fibrillation

Stellate ganglion block is a technique that is often used by anesthesiologists for the treatment of complex regional pain syndromes of the upper extremity. This technique interrupts cardiac sympathetic innervation and has been proposed as treatment for refractory arrhythmias. We present the case of a patient with arrhythmias that were refractory to pharmacological treatment, and were finally treated by continuous stellate ganglion block. Left stellate ganglion is a lynchpin of cardiac arrhythmias due to being a structure where the majority of postganglion sympathetic fibers responsible for preferentially innervating the atriventricular node, bundle of His and ventricular mass are originated, fundamentals in the origin and maintenance of ventricular arrhythmias.

Topics: Atrioventricular Node; Autonomic Nerve Block; Bupivacaine; Cardiovascular Agents; Catheters, Indwelling; Combined Modality Therapy; Counterpulsation; Defibrillators, Implantable; Drug Resistance; Electric Countershock; Heart Conduction System; Humans; Male; Middle Aged; Recurrence; Stellate Ganglion; Sympathetic Fibers, Postganglionic; Tachycardia, Ventricular; Ultrasonography, Interventional

Topics: Aged; Asymptomatic Diseases; Cardiovascular Agents; Defibrillators, Implantable; Electric Countershock; Electrocardiography, Ambulatory; Heart Block; Heart Conduction System; Humans; Hypothyroidism; Male; Risk Factors; Tachycardia, Ventricular; Treatment Outcome

Topics: Aged; Cardiovascular Agents; Echocardiography; Electrocardiography; Female; Humans; Stress, Psychological; Tachycardia, Ventricular; Takotsubo Cardiomyopathy; Treatment Outcome

Topics: Aged; Atorvastatin; Cardiovascular Agents; Digoxin; Drug Therapy, Combination; Female; Furosemide; Heptanoic Acids; Humans; Isosorbide Dinitrate; Lisinopril; Nitroglycerin; Pyrroles; Recurrence; Tachycardia, Ventricular; Warfarin

Stress cardiomyopathy is a newly described reversible cardiomyopathy, characterized by transient cardiac dysfunction usually precipitated by intense emotional or physical stress. Apart from the classical apical ballooning syndrome (Takotsubo), it is now increasingly recognized that the spectrum of stress cardiomyopathies is quite wide, with significant individual variations in clinical and morphological pattern. Very recently, it has been suggested that, in young boys in stressful situations, atypical forms of stress cardiomyopathy could be associated with malignant arrhythmias. We describe the case of a 14-year-old boy, in whom stress cardiomyopathy with mid-ventricular ballooning started with an arrhythmic storm.

Topics: Adolescent; Adrenergic Agonists; Anesthesia, General; Cardiovascular Agents; Electric Countershock; Electrocardiography; Epinephrine; Humans; Male; Stress, Psychological; Tachycardia, Ventricular; Takotsubo Cardiomyopathy; Treatment Outcome; Ventricular Fibrillation

The ventricular sense response (VSR) algorithm enforces biventricular pacing on ventricular sensing to maximize biventricular pacing in patients with atrial fibrillation. This report describes a case of recurrent ventricular tachycardia that may be facilitated by this enforced pacing algorithm.

Topics: Aged; Algorithms; Cardiac Pacing, Artificial; Cardiovascular Agents; Defibrillators, Implantable; Electrocardiography; Heart Ventricles; Humans; Male; Pacemaker, Artificial; Tachycardia, Ventricular

The aim of this study was to determine the relations between myocardial revascularization therapy--coronary artery bypass graft (CABG) and coronary angioplasty (PTCA)--and ventricular potentially malignant arrhythmia (VPMA) (coupled VPC, VPC > 10/hour, NSVT--Morganroth classification), in patients (pts) with stable CAD.. 765 patients with stable angina and ventricular potentially malignant arrhythmia were evaluated angiochoronarographically, echographically, by programmed electrical stimulation (PES), standard ECG, Holter ECG, radiologically, and by stress test. From 765 patients with CAD and VPMA 169 pts. (22.9% of cases) were revascularized, 77 pts. (10.06% of cases) by CABG surgery and 82 pts. (10.71% of cases) by PTCA with or without stenting.. From pts. with inducible sustained ventricular tachycardia by programmed electrical stimulation PES + (129 pts. 16.86% of cases), 19 pts. (2.5% of cases) were with CABG vs 9 pts. (1.17% of cases) with PTCA (p > 0.05). In 333 pts. with arrhythmogenic myocardic ischemia detected by Holter ECG/24 hours (Holter +) the distribution of myocardial revascularization was similar (40 pts., 5.22% of cases with CABG vs 46 pts., 6.01% of cases with PTCA) (p > 0.05). The study included 225 pts. with positive stress test, 45 pts. were revascularized, 18 pts. (2.35% of cases) with CABG and 27 pts. (3.52% of cases) with PTCA (p > 0.05). Revascularized pts. represent an increased percent with prior myocardial infarction in the subgroup with CABG vs. PTCA (39% of cases, p < 0.05 vs. 25% of cases, p < 0.05). Revascularized pts. presented similar distributions of VPMA in subgroups with CABG and PTCA.. VPMA was not influenced by myocardial revascularization, CABG or PTCA, the incidence being similar (50.94% vs 47.2%; p < 0.05) with pts. drug treated.

Topics: Adult; Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cohort Studies; Coronary Artery Bypass; Coronary Artery Disease; Electrocardiography; Female; Humans; Male; Middle Aged; Stents; Tachycardia, Ventricular; Treatment Outcome

The prognosis of patients with chronic heart failure (CHF) is poor in both men and women. However, the characteristics of, and effective treatment strategy for, female CHF patients still remain unclear. This study was designed to evaluate the prognosis and characteristics of female patients in a CHF cohort termed the Chronic Heart Failure Analysis and Registry in the Tohoku District.. Of 1,278 patients registered in the cohort, the study population comprised 1,166 symptomatic CHF patients with sufficient data. As compared with male patients, female patients were more likely to be older, have preserved systolic function and non-ischemic etiology of CHF, and underuse standard CHF medications. Although a previous study showed that sex-difference was not a significant prognostic factor in CHF patients, the unadjusted survival analysis revealed an increased event rate in female patients in the present study. Multivariate analysis revealed that older age, diabetes, ventricular tachycardia and anemia were significant prognostic risks in both men and women with CHF.. Female sex had a significant link with elderly CHF patients. Given the explosive increase in elderly patients in Westernized countries, further studies are needed to elucidate the evidence for treatment of female CHF patients.

Topics: Age Distribution; Age Factors; Aged; Aged, 80 and over; Anemia; Asian People; Cardiology; Cardiovascular Agents; Chronic Disease; Diabetes Complications; Drug Utilization; Female; Health Care Surveys; Heart Failure; Humans; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Practice Patterns, Physicians'; Proportional Hazards Models; Prospective Studies; Registries; Risk Assessment; Risk Factors; Sex Factors; Tachycardia, Ventricular; Time Factors; Treatment Outcome; Women's Health

A potential concern about biological pacemakers is their possible malfunction, which might create ventricular tachycardias (VTs).. The purpose of this study was to test our hypothesis that should VTs complicate implantation of HCN-channel-based biological pacemakers, they would be suppressed by inhibitors of the pacemaker current, I(f).. We created a chimeric channel (HCN212) containing the N- and C-termini of mouse HCN2 and the transmembrane region of mouse HCN1 and implanted it in HEK293 cells. Forty-eight hours later, in whole-cell patch clamp recordings, mean steady state block induced by 3 microM ivabradine (IVB) showed HCN1 = HCN212 > HCN2 currents. The HCN212 adenoviral construct was then implanted into the canine left bundle branch in 11 dogs. Complete AV block was created via radiofrequency ablation, and a ventricular demand electronic pacemaker was implanted (VVI 45 bpm). Electrocardiogram, 24-hour Holter monitoring, and pacemaker log record check were performed for 11 days.. All dogs developed rapid VT (>120 bpm, maximum rate = 285 +/- 37 bpm) at 0.9 +/- 0.3 days after implantation that persisted through 5 +/- 1 days. IVB, 1 mg/kg over 5 minutes, was administered during rapid VT, and three dogs received a second dose 24 hours later. While VT terminated with IBV in all instances within 3.4 +/- 0.6 minutes, no effect of IVB on sinus rate was noted.. We conclude that (1) I(f)-associated tachyarrhythmias-if they occur with HCN-based biological pacemakers-can be controlled with I(f)-inhibiting drugs such as IVB; (2) in vitro, IVB appears to have a greater steady state inhibiting effect on HCN1 and HCN212 isoforms than on HCN4; and (3) VT originating from the HCN212 injection site is suppressed more readily than sinus rhythm. This suggests a selectivity of IVB at the concentration attained for ectopic over HCN4-based pacemaker function. This might confer a therapeutic benefit.

Topics: Animals; Benzazepines; Calcium Channels; Cardiac Pacing, Artificial; Cardiovascular Agents; Catheter Ablation; Defibrillators, Implantable; Dogs; Electrophysiology; Ivabradine; Male; Muscle Cells; Rats; Risk Factors; Tachycardia, Ventricular

We examined how repolarization and depolarization abnormalities contribute to the development of extrasystoles and subsequent ventricular fibrillation (VF) in a model of the Brugada syndrome.. Repolarization and depolarization abnormalities have been considered to be mechanisms of the coved-type ST-segment elevation (Brugada-electrocardiogram [ECG]) and development of VF in the Brugada syndrome.. We used high-resolution (256 x 256) optical mapping techniques to study arterially perfused canine right ventricular wedges (n = 20) in baseline and in the Brugada-ECG produced by administration of terfenadine (5 micromol/l), pinacidil (2 micromol/l), and pilsicainide (5 micromol/l). We recorded spontaneous episodes of phase 2 re-entrant (P2R)-extrasystoles and subsequent self-terminating polymorphic ventricular tachycardia (PVT) or VF under the Brugada-ECG condition and analyzed the epicardial conduction velocity and action potential duration (APD) restitutions in each condition.. Forty-one episodes of spontaneous P2R-extrasystoles in the Brugada-ECG were successfully mapped in 9 of 10 preparations, and 33 of them were originated from the maximum gradient of repolarization (GR(max): 176 +/- 54 ms/mm) area in the epicardium, leading to PVT (n = 12) or VF (n = 5). The epicardial GR(max) was not different between PVT and VF. Wave-break during the first P2R-extrasystole produced multiple wavelets in all VF cases, whereas no wave-break or wave-break followed by wave collision and termination occurred in PVT cases. Moreover, conduction velocity restitution was shifted lower and APD restitution was more variable in VF cases than in PVT cases.. Steep repolarization gradient in the epicardium but not endocardium develops P2R-extrasystoles in the Brugada-ECG condition, which might degenerate into VF by further depolarization and repolarization abnormalities.

Topics: Action Potentials; Animals; Cardiovascular Agents; Disease Models, Animal; Dogs; Electrocardiography; Electrophysiologic Techniques, Cardiac; Endocardium; Heart Conduction System; Heart Diseases; Heart Ventricles; Lidocaine; Male; Pericardium; Pinacidil; Tachycardia, Ventricular; Terfenadine; Ventricular Fibrillation

Left ventricular ejection fraction (LVEF) predicts device discharges in patients with implantable cardioverter-defibrillators (ICDs). The relationship between severity of congestive heart failure (CHF) and ICD discharges is less clear.. We prospectively analyzed the association between CHF and risk of appropriate ICD discharges in the Triggers Of Ventricular Arrhythmias (TOVA) study, a cohort study of ICD patients conducted at 31 centers in the United States. Reported shocks were confirmed for sustained ventricular tachycardia (VT) or fibrillation (VF) by analysis of stored electrograms. Proportional hazards models included CHF categorized by New York Heart Association class. Baseline CHF was present among 502 (44%) of 1140 patients; 170 (34%) had class I, 230 (46%) had class II, 97 (19%) had class III, and only 5 (1%) had class IV symptoms. During median follow-up of 212 days, 92 patients experienced 1 or more appropriate ICD discharges. Class III CHF was associated in a statistically significantly manner with ICD discharge for VT/VF (hazard ratio 2.40, 95% CI 1.16 to 4.98), even with adjustment for LVEF. The combination of LVEF <0.20 and class III symptoms resulted in a particularly high risk of shocks for VT/VF (hazard ratio 3.90, 95% CI 1.28 to 11.92).. Class III CHF, an easily accessible clinical measure, is an independent risk factor, along with LVEF, for ventricular arrhythmias that require shock therapy among ICD patients. Whether patients with class III CHF benefit to a greater degree from ICDs and whether aggressive treatment of CHF in ICD patients may prevent ventricular arrhythmias remains to be determined.

Topics: Actuarial Analysis; Aged; Cardiovascular Agents; Death, Sudden, Cardiac; Defibrillators, Implantable; Disease-Free Survival; Electric Countershock; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Risk; Risk Factors; Severity of Illness Index; Stroke Volume; Tachycardia, Ventricular; United States; Ventricular Fibrillation

Coronary artery spasm has been shown to play an important role in the pathogenesis of not only variant angina but also various arrhythmias. We present a case report of coronary vasospasm-induced arrhythmia and review the prevalence, mechanism, prognosis and management of this problem.

Topics: Aged; Angina Pectoris, Variant; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Vasospasm; Female; Humans; Prognosis; Stents; Tachycardia, Ventricular

The role of prostaglandins in the antiarrhythmic effect of ischemic preconditioning (IP) was investigated in pentobarbital-anesthetized rats. In 5 unpreconditioned control rats, 30 min of occlusion of the left coronary artery elicited ventricular tachycardia (VT) and fibrillation (VF), with an average duration of VT and VF of 51 +/- 6 and 43 +/- 4 s, respectively. Frequent ventricular premature beats (VPBs; average 1,249 +/- 145) were also documented in these animals. Thirty minutes of reperfusion after the prolonged coronary occlusion in these animals caused more severe arrhythmias, including irreversible VF. In animals pretreated with IP (n = 5), which was achieved by 3 cycles of 3 min of occlusion followed by 5 min of reperfusion, 30 min of coronary artery occlusion caused neither VT nor VF, but occasional VPBs (average 2 +/- 1, p < 0.001 vs. control). Only occasional VPBs were observed during 30 min of reperfusion in this group. In animals pretreated with indomethacin (1 mg/kg i.v., n = 5) followed by IP, prolonged ischemia and reperfusion led to frequent VPBs but no VT or VF. The average number of VPBs during ischemia and reperfusion in this indomethacin-treated group was less than that of the controls but greater than the IP-only group (p < 0.01). In conclusion, prostaglandins appear to play a role in the protective effect of IP against VPBs during acute ischemia and reperfusion.

Topics: Animals; Arrhythmias, Cardiac; Cardiovascular Agents; Electrocardiography; Heart Rate; Indomethacin; Ischemic Preconditioning, Myocardial; Male; Prostaglandins; Rats; Rats, Sprague-Dawley; Tachycardia, Ventricular; Ventricular Fibrillation

Topics: Adult; Airway Obstruction; Algorithms; Cardiopulmonary Resuscitation; Cardiovascular Agents; Electric Countershock; Electrocardiography; First Aid; Heart Arrest; Humans; Physical Examination; Posture; Respiration, Artificial; Spinal Cord Injuries; Tachycardia, Ventricular; Ventricular Fibrillation

Ventricular tachyarrhythmias present a unique set of stimuli to arterial and cardiopulmonary baroreceptors by increasing cardiac filling pressures and decreasing arterial pressure. The net effect on the control of sympathetic nerve activity (SNA) in humans is unknown. The purpose of this study was to determine the relative roles of cardiopulmonary and arterial baroreceptors in controlling SNA and arterial pressure during ventricular pacing in humans.. Two experiments were performed in which SNA and hemodynamic responses to ventricular pacing were compared with nitroprusside infusion (NTP) in 12 patients and studied with and without head-up tilt or phenylephrine to normalize the stimuli to either the arterial or cardiopulmonary baroreceptors in 9 patients. In experiment 1, the slope of the relation between SNA and mean arterial pressure was greater during NTP (-4.7+/-1.4 U/mm Hg) than during ventricular pacing (-3.4+/-1.1 U/mm Hg). Comparison of NTP doses and ventricular pacing rates that produced comparable hypotension showed that SNA increased more during NTP (P=0.03). In experiment 2, normalization of arterial pressure during pacing resulted in SNA decreasing below baseline (P<0.05), whereas normalization of cardiac filling pressure resulted in a greater increase in SNA than pacing alone (212+/-35% versus 189+/-37%, P=0. 04). Conclusions--These data demonstrate that in humans arterial baroreflex control predominates in mediating sympathoexcitation during ventricular tachyarrhythmias and that cardiopulmonary baroreceptors contribute significant inhibitory modulation.

Topics: Action Potentials; Adult; Baroreflex; Blood Pressure; Cardiac Catheterization; Cardiac Pacing, Artificial; Cardiotonic Agents; Cardiovascular Agents; Humans; Middle Aged; Nitroprusside; Peroneal Nerve; Phenylephrine; Reflex, Abnormal; Sympathetic Nervous System; Tachycardia, Supraventricular; Tachycardia, Ventricular; Tilt-Table Test; Vasodilator Agents; Ventricular Dysfunction, Left

Topics: Administration, Oral; Aged; Atrial Fibrillation; Cardiovascular Agents; Diltiazem; Female; Humans; Infusions, Intravenous; Tachycardia, Ventricular

Arrhythmias induced by coronary artery ligation in cats, by CaCl2 and epinephrine in rats, and by ouabain in guinea-pigs were used as experimental models for studying the effects of a new calcium antagonist AR-1 ([1,2,5-trimethyl-4-phenyl-4-beta-(N-cyanoethyl-N-4'-methoxybenzyl) -ethylamino]piperidine, calcium channel blocker and calmodulin antagonist) on ventricular arrhythmias. Coronary ligation caused 90% lethality (ventricular fibrillation) with 12.5 min in untreated control cats, which was prevented by administration of AR-1 (4 mg/kg body weight (b.w.) before or after arrhythmia induction. Pretreatment with AR-1 afforded protection in a dose-related fashion. A dose of 1.5 mg/KG b.w. increased survival to 45%, and all cats dosed with 3 to 5 mg/Kg b.w. survived. CaCl2 (180 mg/Kg b.w., i.v.) induced ventricular fibrillation and 100% lethality. These effects were completely prevented by an anti-arrhythmic dose of AR-1 (3 mg/kg b.w.). Epinephrine-induced ventricular arrhythmias were also prevented by the same dose of AR-1. AR-1 (5 mg/kg b.w.) did not prevent ouabain (0.5 mg/kg b.w.)-induced arrhythmias that caused death within 17 +/- 3.7 min, but displayed protective effects during 67 +/- 7.7 min. The results from these animal studies, in conjunction with previously studies demonstrating coronarodilatory and anti-platelet efficacy of this compound, collectively suggest that AR-1 has a potential to become a useful antianginal and antiarrhythmic therapeutic agent.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Calcium Channel Blockers; Calcium Chloride; Cardiovascular Agents; Coronary Vessels; Electrocardiography; Epinephrine; Male; Ouabain; Piperidines; Rats; Rats, Wistar; Tachycardia, Ventricular; Ventricular Fibrillation

Sinus tachycardia facilitates ventricular conduction delay and sustained ventricular tachyarrhythmias during tricyclic antidepressant overdose. We hypothesized that impeding sinus tachycardia with the specific bradycardia agent, UL-FS 49, would reduce the incidence of ventricular tachyarrhythmia caused by tricyclic antidepressant overdose and tested this hypothesis in a canine model of ventricular tachycardia (VT) induced by graded amitriptyline infusion (0.5-1.0 mg/kg/min) during continuous hemodynamic monitoring. Three groups were studied. A control group (group A, n = 8) received amitriptyline infusion alone. A pretreated group (group B, n = 8) received UL-FS 49 (1 mg/kg intravenously, i.v.) 45 minutes before amitriptyline infusion. A treatment group (group C, n = 5) received UL-FS 49 (1 mg/kg) during amitriptyline infusion after onset of ventricular tachyarrhythmia. Seven (88%) in group A had ventricular tachyarrhythmia at 35 +/- 6 min of amitriptyline infusion. Ventricular tachyarrhythmia did not occur in any (0%) animal in group B. Peak sinus heart rate (HR) was significantly higher in group A (160.0 +/- 9.8 beats/min) than in group B (92.8 +/- 5.3 beats/min; p < 0.0001). Unimpeded sinus tachycardia in group A was associated with a significantly longer QRS duration (158.8 +/- 7.4 ms) as compared with group B (101.0 +/- 2.3 ms; p < 0.0001). UL-FS 49 did not influence systolic blood pressure (SBP) at baseline or during amitriptyline infusion. In group C, 3 of 5 dogs with nonsustained VT (NSVT) had effective sinus rate slowing and suppression of all NSVT after UL-FS 49. UL-FS 49 did not terminate SVT in 2 of 5 group C dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amitriptyline; Animals; Benzazepines; Cardiovascular Agents; Dogs; Electrocardiography; Female; Male; Tachycardia, Ventricular