Treatment Of Malignant Ventricular Arrhythmias Research Articles

Design and rationale of the MODULAR ATP global clinical trial: A novel intercommunicative leadless pacing system and the subcutaneous implantable cardioverter-defibrillator.

The subcutaneous implantable cardioverter-defibrillator (S-ICD) has demonstrated safety and efficacy for the treatment of malignant ventricular arrhythmias. However, a limitation of the S-ICD lies in the inability to either pace-terminate ventricular tachycardia or provide prolonged bradycardia pacing support. The rationale and design of a prospective, single-arm, multinational trial of an intercommunicative leadless pacing system integrated with the S-ICD will be presented. A technical description of the modular cardiac rhythm management (mCRM) system (EMPOWER leadless pacemaker and EMBLEM S-ICD) and the implantation procedure is provided. MODULAR ATP (Effectiveness of the EMPOWER™ModularPacing System and EMBLEM™ Subcutaneous ICD to Communicate Antitachycardia Pacing) is a multicenter, international trial enrolling up to 300 patients at risk of sudden cardiac death at up to 60 centers trial design. The safety endpoint of freedom from major complications related to the mCRM system or implantation procedure at 6 months and 2 years are significantly higher than 86% and 81%, respectively, and all-cause survival is significantly >85% at 2 years. Efficacy endpoints are that at 6 months mCRM communication success is significantly higher than 88% and the percentage of subjects with low and stable thresholds is significantly higher than 80%. Substudies to evaluate rate-responsive features and performance of the pacing module are also described. The MODULAR ATP global clinical trial will prospectively test the safety and efficacy of the first intercommunicating leadless pacing system with the S-ICD. This trial will allow for robust validation of device-device communication, pacing performance, rate responsiveness, and system safety.

Medicinska sestra u timu za izvodjenje epikardneablacije

Any disturbance of the normal heart rhythm , during which there is an increase or decrease in frequency (heart rate) or similar abnormalities is called cardiac arrhythmia. There are different types of arrhythmias which can be divided into: atrial fibrillation (atrial flicker), premature ventricular contraction, WPW syndrome, ventricular tachycardia, bradycardia end ventricular fibrillation (life-threatening). The causes of arrhythmias may be acute myocardial infarction, mitral valve prolapse, cardiomyopathy, myocarditis, congenital heart defects, valvular heart disease, caffeine, drugs, stress…. Epicardial ablation is an invasive non-surgical treatment of arrhythmias and is used in the treatment of malignant ventricular arrhythmias. It is performed under local anesthesia in the following way: a catheter is introduced by the physician into the pericardial sack and the outside of the heart, to search for the spot that is causing arrhythmias (usually in bundles or lumps at particular place in the heart), using X-ray images and EKG records obtained from the catheter tip for navigation. Once the right position has been found, the tip of the catheter is heated by radio frequency energy, allowing for small, deliberate damage to be done to parts of the muscle (1-2mm in size), which breaks the conductive wisp or destroys the activity of the nodes that cause arrhythmias . In well-selected patients, this is currently the method of choice in treatment because it may cure, or cause a complete cessation of arrhythmias in perpetuity, without the need for further drug taking.

Perforación cardiaca como complicación tardía en paciente portador de un Desfibrilador Automático Implantable

A 55-year-old man with an implantable cardioverter-defibrillator (ICD) placed after diagnosis of Brugada syndrome 4 years earlier was admitted to hospital with dyspnea and a large left pleural effusion. After several episodes of cardiorespiratory arrest and application of advanced cardiac life support measures, an emergency sternotomy was performed. Cardiac and pleural perforation by the ICD lead was observed and the device was removed. Since the ICD was introduced in 1980, it has been effective in the treatment of malignant ventricular arrhythmias and in reducing the incidence of sudden death. Increased use, however, has meant a rise in the number of complications, some of which are potentially fatal. The rare complication we describe should therefore be considered whenever a patient with an ICD develops sudden respiratory failure or massive hemoptysis that cannot be explained by other causes.

Desfibrilador implantable en el manejo de taquiarritmias ventriculares malignas: Experiencia del Centro Nacional de Arritmias

Implantable defibrillators are the most effective means to prevent sudden death in patients with malignant ventricular tachyarrhythmias. The availability of this type of devices is limited in Chile, due to their high price. To report the first patients treated with implantable defibrillators in our hospital. Nine males and one female aged 13 to 65 years old are reported. Three presented with ventricular fibrillation (presenting out of the hospital in three) and the rest had ventricular tachycardia resistant to drugs or radiofrequency ablation. All implants were performed using intracardiac electrodes. The generator was implanted in the pectoral region in nine and in the abdomen in one. A successful defibrillation was obtained with less than 15 J in four patients, with 20 J in three and with 24 J in three. There were no complications during the procedure. After a 12 months follow up, four patients have been treated by the implantable device. One of these subjects had a ventricular fibrillation in two occasions. One patient died of a bronchopneumonia two years after the implant. Implantable defibrillators are an effective therapy for the treatment of malignant ventricular arrhythmias with a high risk of sudden death.

Nonpharmacological therapy for malignant ventricular arrhythmias: Implantable defibrillator trials

Implantable cardioverter-defibrillators (ICDs) are an important nonpharmacological option in the treatment of malignant ventricular arrhythmias. Technological advances in current devices permit nonthoracotomy implantation with transvenous lead systems using biphasic shocks. Decreasing device size has resulted in pectoral implantation. Battery longevity is still short in comparison with that of pacemakers. Lead failure rates as well as pacing thresholds are significantly higher than those for cardiac pacing lead systems. Other complications of ICD systems include infection, perforation, and thrombosis. The long-term performance of nonthoracotomy lead systems for ICD devices has now been extensively studied. Sudden death recurrence rates for these systems are less than 2% in 3 years and less than 5% at 5 years. Clinical trials with both monophasic and biphasic systems show a high degree of prevention of sudden death. Comparison of ICD outcome with that of drug therapy in three large retrospective studies and two small prospective randomized trials favors improved survival and sudden death prevention with device therapy. However, these studies need corroboration from large prospective trials. Two large prospective trials, CIDS and the AVID study, are now in progress to address this issue.

The implantable cardioverter defibrillator: the end of the thoracotomy approach.

Internal cardioverter defibrillator (ICD) implantation has become a standard therapy for life-threatening arrhythmias. A simple and safe surgical implantation technique is therefore mandatory in this high risk population. In a 30-month period 86 patients received 87 ICD devices. An endocavitary lead system was used as first choice in 62 patients and defibrillation thresholds (DFT) of 25 joules (J) or less were obtained in 57 patients. A thoracotomy approach was avoided using a biphasic shock wave form in 17 patients and the addition of a subcutaneous (sc) patch in 11 patients or wire array lead in 9 patients. There was one early non-technique related death (1.7%) after the transvenous approach. Reoperation was necessary in three patients with lead complications and in two patients for local device problems (one migration, one infection). With the recent progress in ICD technology, a thoracotomy approach could be avoided for the last 52 patients. For comfort and cosmetic reasons left subcostal insertion of the device has been successfully used in the last 50 patients. We conclude that the nonthoracotomy approach can now be offered to all patients in need for an ICD as a consequence of the technological progress made in the field of electric treatment of malignant ventricular arrhythmias. A stepwise approach with a minimum of implanted hardware and the use of biphasic shock systems now offers a simple and efficient treatment alternative with very low perioperative risk. Internal cardioverter defibrillator implantation in combination with open heart procedures can easily be avoided.

Surgical revascularization in the treatment of ventricular tachycardia and fibrillation exposed by exercise-induced ischaemia.

The role of myocardial revascularization in the treatment of malignant ventricular arrhythmias is not well defined. Our hypothesis was that in patients with ventricular tachycardia or fibrillation exposed by exercise-induced ischaemia, the acute transient ischaemia plays a principal causal role, and that in these patients surgical myocardial revascularization alone might be an effective treatment. Among 1100 consecutive patients undergoing isolated coronary artery bypass surgery (CABG) 30 patients (2.7%) characterized by ventricular tachycardia or fibrillation at the symptom-limited exercise tests prior to revascularization were studied prospectively. All patients had exercise-induced angina pectoris or ischaemic ST-segment depression preceding at least one of the arrhythmic events. In addition, eight of these 30 patients had experienced syncope during out-of-hospital exertional activities. After surgical revascularization, the 28 patients surviving to hospital discharge were followed for 1.6 to 86 months (mean 29 +/- 29 months) as outpatients and underwent between one to eight exercise tests (mean 2.6 +/- 1.9). One of these patients died suddenly of unknown causes at 14 months, another from cancer at 53 months. Twenty-six patients experienced a total of 34 episodes of ventricular tachycardia before revascularization. Two of these patients, both having residual ischaemia, had arrhythmia recurrences during follow-up; odds ratio (OR) 84.5, 95% confidence interval (CI) 18.7-381.9; P = < 0.010. Exercise-induced ventricular fibrillation occurred in eight patients pre-operatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Experience with three different third-generation cardioverter-defibrillators in patients with coronary artery disease or cardiomyopathy

Clinical investigations are being performed in multiprogrammable devices whose therapeutic options include antitachycardia pacing, cardioversion, defibrillation and bradycardia pacing. Three different third-generation devices were implanted in 46 research patients at 1 clinical center to document their safety and efficacy for the treatment of malignant ventricular arrhythmias. Additionally, the purpose of the study was to determine if antitachycardia pacing is a desirable and frequently used feature of tiered devices. The Medtronic PCD was implanted in 15 patients (12 men, mean age 60 ± 13 years, mean ejection fraction 40 ± 15%), the Ventritex Cadence in 21 patients (17 men, mean age 65 ± 10 years, mean ejection fraction 38 ± 12%), and the CPI VENTAK PRx in 10 patients (8 men, mean age 63 ± 14 years, mean ejection fraction 31 ± 8%). All patients presented with cardiac arrest or ventricular tachycardia. During follow-up of 10 ± 6 months (range 1 to 19), 70% of the 20 patients with antrtachycardia pacing activated used the feature for spontaneous ventricular tachycardia. The antrtachycardia pacing parameters were reprogrammed 20 times in 15 patients. Two thousand six hundred thirty-eight of 2,675 (98%) antrtachycardia pacing attempts successfully terminated spontaneous tachyarrhythmias. Low-energy cardioversion or defibrillation terminated tachyarrhythmias in patients where pacing was unsuccessful. One hundred forty-eight episodes of tachycardia were successfully treated directly by shocks in 16 of 46 patients (35%). There were no deaths due to device failure. This initial single-center clinical experience suggests that the PCD, Cadence and VENTAK PRx are all safe and effective tiered therapy devices for the treatment of malignant ventricular arrhythmias. Antrtachycardia pacing successfully terminated most episodes of ventricular tachycardia; in patients with this feature activated, it was used frequently but required reprogramming to achieve high levels of success.

Propafenone. A reappraisal of its pharmacology, pharmacokinetics and therapeutic use in cardiac arrhythmias.

Propafenone is an orally active sodium channel blocking agent with beta-adrenoceptor antagonist and weak calcium antagonist activity. The pharmacokinetic profile of propafenone is complex, characterised as typically nonlinear, saturable, stereoselective and dependent on both dose and debrisoquin metaboliser phenotype; individualised dosage titration is required. Both placebo- and drug-controlled studies have confirmed the efficacy of propafenone in the treatment of premature ventricular complexes, ventricular couplets and nonsustained ventricular tachycardia; in a large meta-analysis, propafenone together with amiodarone, flecainide and encainide were significantly more effective in the control of ventricular ectopy than other antiarrhythmic agents. However, the use of propafenone in these indications, like that of other antiarrhythmic agents, is likely to be limited to patients with a favourable risk-to-benefit ratio. Propafenone has also demonstrated efficacy in the treatment of malignant ventricular arrhythmias (ventricular fibrillation and sustained ventricular tachycardia); preliminary mortality data obtained with propafenone have been encouraging in this patient group. In addition, propafenone has a favourable noncardiac tolerability profile and beta-adrenoceptor antagonist activity, which may offer advantages in some specific patient groups. The area of research concerning propafenone which has shown the greatest expansion over the past 5 years is in the treatment of supraventricular arrhythmias. Propafenone has marked efficacy in patients with Wolff-Parkinson-White syndrome and has been recommended as a first-line prophylactic agent in those with rapid anterograde conduction. Propafenone is also effective in the conversion of atrial fibrillation to sinus rhythm, although comparative studies are required to determine advantages over more established agents. Propafenone use has been successfully extended to children with limited data demonstrating consistent efficacy in the control of junctional ectopic tachycardia. As with all antiarrhythmic agents, propafenone has the potential to induce arrhythmias. Comparative studies are required to assess in more detail the cardiac tolerability profile of propafenone against other class Ic agents. In conclusion, propafenone offers a broad spectrum of activity in the treatment of cardiac arrhythmias, although its use in patients with potentially malignant arrhythmias will remain limited for the present. Due to its unique pharmacodynamic profile, propafenone deserves consideration as an individual agent.

Moricizine: pharmacodynamic, pharmacokinetic, and therapeutic profile of a new antiarrhythmic.

Moricizine (Ethmozine) is a phenothiazine derivative recently approved in the United States for the treatment of malignant ventricular arrhythmias. Moricizine closely resembles group IA antiarrhythmic agents in the intensity of its effect on the sodium channel, but it differs from the IA subclass in that it shortens the action potential duration in ventricular tissue. Moricizine suppresses frequent ventricular premature depolarizations and nonsustained ventricular tachycardia in 60% to 70% of patients, and it suppresses induced ventricular tachycardia in 15% to 25% of patients. It is well tolerated, with a low incidence of adverse effects. The suggested dosage is 600 to 900 mg per day in three divided doses. Treatment of arrhythmias with prognostic significance should be initiated in the hospital, and monitored with electrophysiologic studies. Additional clinical experience is needed to better define moricizine's role in antiarrhythmic therapy.

Propafenone: A Promising New Antiarrhythmic Agent

Propafenone is a new class IC antiarrhythmic agent that has just been released in the United States for use in treatment of malignant ventricular arrhythmias (Rythmol, Knoll Pharmaceuticals, Whippany, New Jersey). It was first marketed in Europe in 1977, and has gained wide acceptance there and in Canada for the treatment of various types of ventricular and supraventricular arrhythmias. It acts primarily by inhibiting the fast inward sodium current. Like flecainide and encainide, it has very prominent conduction slowing effects, with relatively little change in repolarization and corrected QT interval.

Lidocaine in the early phase of acute myocardial infarction: The controversy over prophylactic or selective use

In acute myocardial infarction, lidocaine is considered the drug of choice for the treatment of malignant ventricular arrhythmias. While initially a so-called "selective" treatment strategy prevailed, in which lidocaine was administered only after the onset of certain "warning arrhythmias," the prophylactic use of lidocaine in acute myocardial infarction has been gaining wider usage in intravenous and intramuscular application in recent years. Both therapeutic applications have been found to be problematic of late, which has led to increasingly restrictive use of lidocaine. While in selective treatment forms, the definition and prompt recognition of the so-called warning arrhythmias created especially acute problems, the prophylactic therapeutic use is problematic due to the occurrence of sometimes serious side effects, which is to be expected as the size of the collective being treated increases. Both treatment forms also appear limited by the narrow preventive efficacy of lidocaine against malignant ventricular arrhythmias, especially against ventricular fibrillation. The current therapeutic recommendation for lidocaine in acute myocardial infarction should be limited to patients presenting with very frequent and complex ventricular arrhythmias, especially when these are elicited by an R-on-T phenomenon. Side effects and other therapeutic problems encountered when the therapeutic modality is switched or adjusted can be greatly reduced by careful dosing and selection of the optimal combination substances.

Efficacy of moricizine in malignant ventricular arrhythmias

Moricizine hydrochloride has been shown to be effective in the treatment of a variety of ventricular arrhythmias. It has been evaluated for the treatment of malignant ventricular arrhythmias in several hundred patients. When assessed by noninvasive techniques, moricizine effectively suppresses spontaneous unsustained ventricular tachycardia (VT) in approximately 60% of patients. Efficacy is sustained during long-term therapy. Evaluation of moricizine therapy for sustained VT using programmed stimulation has been carefully performed in more than 100 patients. The initiation of sustained VT is suppressed in 20 to 25% of patients. Moricizine is generally well tolerated. Because of its minimal effects on left ventricular function, a common clinical problem in patients with malignant ventricular arrhythmias and relatively low potential for proarrhythmia, moricizine has a role in the treatment of malignant ventricular arrhythmias in selected patients.

RE-EMPLOYMENT AFTER DEFIBRILLATOR IMPLANTATION.

The implantable automatic cardioverter defibrillator (ACD), the most recent addition to the treatment of malignant ventricular arrhythmias, appears to

Tetrodotoxin: sodium channel specific anti-arrhythmic activity.

Many Class I anti-arrhythmic drugs not only block the cardiac sodium channel but also block the calcium and/or potassium channels. The hypothesis tested in this study was that sodium channel blockade without blockade of calcium or potassium channels produced anti-arrhythmic activity in the treatment of malignant ventricular arrhythmias. The arrhythmia model consists of ventricular fibrillation induced by critically timed single extrastimuli at twice diastolic pacing threshold following 15 minutes of ischaemic injury in a rabbit heart perfused in vitro. Preparations were randomly assigned to either tetrodotoxin (a selective sodium channel blocking toxin) or vehicle. Ventricular fibrillation occurred in all vehicle treated preparations in response to single extrastimuli following ischaemic injury. Treatment with tetrodotoxin at concentrations of 0.1 to 1.0 micromolar protected some hearts from fibrillation, while at concentrations above 3 micromolar ventricular fibrillation was not inducible. Tetrodotoxin produced concentration dependent increases in ventricular effective refractory period and conduction time in the infarct zone which were associated with anti-arrhythmic activity. No concentration dependent change in action potential duration was seen with tetrodotoxin. Thus the electrophysiological and anti-arrhythmic activities of tetrodotoxin in this model demonstrate that the property of selective sodium channel blockade is sufficient to produce anti-arrhythmic activity.

Drug Interactions with Propafenone

Propafenone is a Class IC antiarrhythmic drug that has been under investigation for over 10 years and is on the threshold of release for general use. Clinical trials have been completed that present compelling evidence of the safety and efficacy of the drug for the treatment of malignant ventricular arrhythmias. As with other potent antiarrhythmic agents, propafenone has the propensity to interact with a variety of other drugs, and these interactions are of critical importance to physicians who will prescribe the drug to patients with cardiac arrhythmias. A particularly detailed knowledge of the interactions between propafenone and such commonly used drugs as anticoagulants, digoxin, cimetidine, other antiarrhythmics, and even food is essential to its safe administration. This paper reviews current information regarding the drug interactions of propafenone so that, once released and available, it will be used appropriately and safely.

Efficacy and tolerance of tocainide during long-term treatment of malignant ventricular arrhythmias.

A group of 51 patients with malignant ventricular arrhythmias refractory to standard oral antiarrhythmic agents were treated with oral tocainide. Antiarrhythmic efficacy was defined as total abolition of occurrences of ventricular tachycardia (VT) or ventricular fibrillation (VF) as assessed by hospital admissions for arrhythmias and the occurrence of sudden cardiac death (SCD). Of the 51 patients, 32 (63%) initially tolerated tocainide and were discharged from the hospital. Of the 19 patients not initially responding to tocainide, 6 (12%) had arrhythmia recurrence and 13 (25%) developed intolerable central nervous system or gastrointestinal side effects. Of these 19 short-term nonresponders, 8 (42%) patients suffered SCD over an average follow-up of 24 months (annual SCD rate of 21%). Two patients suffered SCD during the first week of tocainide therapy. Discounting the 2 patients with SCD on tocainide therapy, 6 of 17 (35%) patients initially withdrawn from tocainide suffered SCD (annual SCD rate of 18%). Twenty-four of the 32 short-term responders did not have arrhythmia recurrence over a mean follow-up of 38 months resulting in an overall long-term efficacy of 47% (24/51). Over an average follow-up of 38 months for these 24 short-term responders, 12 patients expired from nonarrhythmic causes, 3 patients were withdrawn for non-drug-related causes, and 9 patients remain on tocainide therapy. Of the 8 long-term nonresponders, 3 patients had arrhythmia recurrence and died suddenly while 5 patients developed intolerable side effects. The annual SCD rate in short-term responders was 3%. Eighteen of the 51 patients (35%) were withdrawn from the study because of adverse effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of malignant ventricular arrhythmias with endocardial resection and implantation of the automatic cardioverter-defibrillator.

Although ventricular resection guided by endocardial mapping has been a successful treatment for drug-refractory ventricular arrhythmias, 20 to 30 percent of patients still have postoperative sustained ventricular tachycardia or sudden death. To improve the outcome of the procedure, we implanted an automatic cardioverter-defibrillator in conjunction with endocardial resection in 28 patients, all of whom had had previous myocardial infarctions and between one and five cardiac arrests. There were three perioperative deaths. During follow-up of 8 to 51 months (mean, 25), 4 of the 25 survivors had recurrences of hypotensive ventricular tachycardia, which in all instances were automatically terminated by the implanted device. One patient, whose automatic cardioverter-defibrillator was not functional, died suddenly. We conclude that patients undergoing mapping-directed endocardial resection can be provided with additional protection against recurrent ventricular tachyarrhythmias or sudden death by implantation of an automatic cardioverter-defibrillator.

Efficacy of amiodarone during long-term treatment of malignant ventricular arrhythmias in patients with chronic chagasic myocarditis

Oral amiodarone was administered to 24 patients with chronic chagasic myocarditis (CCM) and malignant ventricular arrhythmias. Control 24-hour Holter recordings revealed frequent ventricular premature beats (VPBs) (157 to 2572/hr; mean 714 ± 125), multiform VPBs, and countless numbers of ventricular couplets in all patients, R-on-T phenomenon in 17 patients, and ventricular tachycardia in 21 patients. Amiodarone caused total and persistent suppression of ventricular couplets and tachycardia and greater than 93% reduction of VPB number in 22 patients, during a follow-up of 26.6 months (range 2 to 55 months). In 1 patient, ventricular couplets and tachycardia persisted despite the fact that a 98.2% reduction of VPB number was achieved. This latter patient was the only one in the whole group who experienced sudden death. The maximal antiarrhythmic effect was attained gradually after 3 to 26 weeks (mean 7.4). In four patients in whom treatment was discontinued after 3 to 12 months, the antiarrhythmic protection lasted 4 to 9 weeks. In nine patients the dose of amiodarone was 600 to 800 mg/day. In 15 patients the dose had to be increased to 800 to 1000 mg/day. Despite the presence of congestive heart failure in seven patients and intraventricular block in 17 patients, no limiting side effects were observed. Amiodarone proved to be extremely effective and safe against the most malignant ventricular arrhythmias of CCM.

The Treatment of Malignant Ventricular Arrhythmias with Combined Endocardial Resection and Implantation of the Automatic Defibrillator: Preliminary Report

Fourteen patients with refractory ventricular tachyarrhythmias were treated with combined endocardial resection and implantation of the automatic defibrillator. There were 11 men and 3 women with a mean age of 53 years (range, 41 to 58 years). All patients had coronary artery disease; the mean ejection fraction was 26%, and the mean number of cardiac arrests was 2.6. Programmed electrical stimulation induced sustained ventricular tachycardia in 13 patients and nonsustained ventricular tachycardia in 1. Operative endocardial mapping in the 13 patients with sustained ventricular tachycardia demonstrated a septal focus of early activation in 9 patients and a nonseptal site in 4. Following resection, sustained ventricular tachycardia could not be reinduced. There was 1 operative death. Programmed electrical stimulation performed one month after operation induced ventricular tachycardia in 5 patients, but tachycardia could not be induced in the other 8 survivors. The longest follow-up was 32 months; the average was 17 months. There were 2 late deaths. One patient died of myocardial infarction and 1 of pulmonary edema following a routine cholecystectomy. In another patient, late ventricular tachycardia developed but was automatically terminated by the implanted defibrillator. These results suggest that endocardial resection combined with implantation of the automatic defibrillator may offer the greatest protection yet available to patients with malignant ventricular tachyarrhythmias.