Adenosine in the mammalian heart: nothing to get excited about.

Until quite recently, the cardiodepressant actions of adenosine were widely accepted. A nucleoside that produces negative chronotropic and ionotropic effects, adenosine, has been used clinically as the drug of choice for terminating supraventricular (atrioventricular node) tachycardia and is likely to play an important part in regulating arrhythmogenic activity as an endogenous antiarrhythmic metabolite. Despite this, recent experimental data, particularly resulting from in vitro studies using animal models, have shown a paradoxical excitable action of adenosine in the heart. In this article, Amir Pelleg and Steven Kutalek present the reasons why they continue to believe that any excitatory actions of adenosine in the heart are clinically irrelevant.

Reduction in sudden death and total mortality by antiarrhythmic therapy evaluated by electrophysiologic drug testing: criteria of efficacy in patients with sustained ventricular tachyarrhythmia.

Reports of the results of electrophysiologic testing of antiarrhythmic regimens have concentrated on inducibility of ventricular tachycardias during drug treatment. Many drug regimens, however, affect the tachycardia but fail to prevent its initiation. In this study, 258 patients who underwent serial electrophysiologic studies were followed up. The patients were divided into three groups on the basis of the results of electrophysiologic testing. Group 1 included patients in whom the initiation of ventricular tachycardia was prevented by the drug regimen. In groups 2 and 3 the ventricular tachycardia was still inducible with the discharge drug regimen. In group 2, the drug regimen demonstrated a beneficial response (that is, the tachycardia cycle length increased by greater than 100 ms and the tachycardia did not produce severe symptoms). In group 3, the regimen did not produce a beneficial response. During follow-up, recurrence of sustained ventricular tachycardia occurred in 7 (7%) of 103 group 1 patients but in 20 (39%) of 51 and 52 (50%) of 104 group 2 and 3 patients, respectively. However, the total mortality and sudden death mortality rates were substantially reduced in group 2 (12 and 4%, respectively) compared with group 3 (39 and 34%). In fact, the total mortality and sudden death mortality in groups 1 and 2 were not significantly different. Thus, under certain circumstances, a drug regimen that produces a beneficial response may be an acceptable clinical alternative, particularly when no regimen prevents induction of ventricular tachycardia.

Risks and complications of clinical cardiac electrophysiologic studies: a prospective analysis of 1,000 consecutive patients.

The complications of clinical cardiac electrophysiologic studies were prospectively evaluated in 1,000 consecutive patients studied in one laboratory with an unaltered protocol to better assess the risks of this procedure. There were 728 men and the mean age of the entire group was 58 years (range 16 to 84). Coronary artery disease was the most common type of heart disease (56%) and 200 patients had no identifiable organic heart disease. The indication for study was a ventricular tachyarrhythmia or cardiac arrest in 582 patients. Each patient underwent an initial (baseline) study and 444 patients underwent serial drug studies (2.7/patient). There was one death during these studies. Other major complications included arterial injury (0.4%), thrombophlebitis (0.6%), systemic arterial embolism (0.1%), pulmonary embolism (0.3%) and cardiac perforation (0.2%). Significant arrhythmic complications included catheter-induced permanent complete atrioventricular (AV) block in 1 patient, nonclinical atrial fibrillation that required therapy in 10 patients and severe proarrhythmic events in 12 (3%) of 397 patients undergoing drug studies for ventricular tachyarrhythmias. Cardioversion was required for termination of ventricular tachyarrhythmias in 179 baseline studies (53% of patients with inducible arrhythmia), and in an additional 35 patients, cardioversion was required at least once during follow-up studies. Although clinical cardiac electrophysiologic studies are associated with complications, the risks are small and acceptable.

Efficacy and safety of catheter ablation in octogenarians.

OBJECTIVES: To determine whether catheter ablation is safe and effective in patients over the age of 80. BACKGROUND: There is a tendency to withhold invasive therapy in the elderly until it has been proven safe and effective. METHODS: Over a two-year period from February 1, 1996 to February 1, 1998, 695 consecutive patients underwent 744 catheter ablation procedures of supraventricular and ventricular arrhythmias. These patients were divided into three groups based on age: > or =80 years, 60 to 79 years and <60 years. Acute ablation success, using standard criteria and complication rates for these three groups were determined. RESULTS: There were 37 patients > or =80 years, 275 patients 60 to 79 years and 383 patients <60 years old. The overall acute ablation success rate for the entire group was 95% with no difference in rates among the three groups (97%, > or =80 years; 94%, 60-79 years; 95%, <60 years). The percentage of patients undergoing His bundle ablation was greatest in the > or =80-year-old group (43% vs. 19% vs. 2%, p < 0.01), and the percentage of patients undergoing accessory pathway ablation was greatest in the <60-year-old patients (0% vs. 4% vs. 25%, p < 0.01). The overall complication rate for the entire group was 2.6%, and there was only one major/life-threatening complication. There was no difference in complication rates among the groups (0%, > or =80 years; 2.2%, 60 to 79 years; 3.1%, <60 years). Based on the sample size, the 95% confidence interval is 0% to 7.8% for an adverse event in the octogenarian. CONCLUSIONS: Catheter ablative therapy for the arrhythmias attempted in the very elderly appears to be effective with low risk. Ablation results appear to be comparable with those noted in younger patients.

Electrophysiologic assessment of antiarrhythmic drug efficacy for ventricular tachyarrhythmias associated with dilated cardiomyopathy.

To determine the benefit of serial electrophysiologic drug testing in patients with ventricular tachyarrhythmias related to dilated cardiomyopathy, programmed ventricular stimulation was performed in 38 patients. In the baseline study, sustained ventricular tachycardia (VT) was induced in 18 patients, ventricular fibrillation in 7 and nonsustained VT in 13. The patients underwent a total of 84 trials of drug therapy (mean 2.3 +/- 1.4 trials/patient). Complete success (induction of fewer than 6 repetitive responses) was recorded in 19 trials and partial success (induction of at least 6 but no more than 15 repetitive responses) in 7. Potential proarrhythmic effects were observed in 9 trials. Overall, at least 1 successful regimen was identified for 20 patients (53%). During a mean follow-up of 21 +/- 13 months, there were no arrhythmia recurrences or episodes of sudden death among patients discharged with a drug regimen determined to be effective by serial drug testing. In comparison, among patients taking regimens that failed to prevent arrhythmia induction, there were 3 arrhythmia recurrences and 2 sudden deaths (p less than 0.05). Serial electrophysiologic drug testing provides an effective method of identifying successful medical therapy for patients with ventricular arrhythmia related to dilated cardiomyopathy.

Relation of acute antiarrhythmic drug efficacy to left ventricular function in coronary artery disease.

This study assessed the relation between acute antiarrhythmic drug efficacy and left ventricular (LV) function in patients with sustained ventricular tachyarrhythmias, that is, sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Electrophysiologic studies (n = 560) were performed in 201 patients, separated for analysis into less than 30 and greater than or equal to 30% ejection fraction groups. Coronary artery disease was present in all patients. The 8 acute antiarrhythmic regimens were procainamide, quinidine, mexiletine, mexiletine + type 1A agent, flecainide or indecainide, amiodarone, amiodarone + type 1A and "miscellaneous" agents. At least 1 successful acute antiarrhythmic regimen was found in 47% of patients and in a significantly greater proportion of patients with ejection fraction greater than or equal to 30% (52 of 81 = 64%) than in those with ejection fraction less than 30% (43 of 120 = 36%, p less than 0.001). Drug trials were successful (initiation of less than 15 repetitive ventricular responses) in 32% of patients with ejection fraction greater than or equal to 30% versus 19% of those with ejection fraction less than 30% (p less than 0.001). There were no statistically significant differences between the 2 ejection fraction groups in type of heart disease, acute antiarrhythmic dosages or mean serum drug levels. A logistic regression analysis incorporating multiple clinically relevant factors found that ejection fraction was the only factor that correlated significantly with drug success or failure (p less than 0.002). Acute antiarrhythmic drug efficacy relates to LV function per se or to other pathophysiologic mechanisms of which ejection fraction may be a marker.

Feasibility, safety, and determinants of extraction time of percutaneous extraction of endocardial implantable cardioverter defibrillator leads by intravascular countertraction method.

Previous studies of the removal of implantable cardioverter defibrillator (ICD) leads have been restricted to case reports or small series. In this report, we describe our experience in ICD lead extraction by intravascular countertraction method using Cook's extraction kit. A total of 47 high-voltage (HV) leads, 3 rate sensing (S) leads, and 2 subcutaneous arrays were removed from 42 patients (33 men, 9 women; mean age 59 years [range 14 to 81]). One HV superior vena cava (SVC) lead and 11 HV right ventricular (RV) leads were explanted by manual traction only and defined in the "lead removal" category. One S lead was removed using a femoral venous approach. The remaining 37 leads were explanted by SVC approach using extraction sheaths and defined in the "lead extraction" category. Twenty leads were extracted for "infectious" (group A) and 17 leads for "noninfectious" (group B) etiologies for which extraction times of 27.0+/-18.0 and 27.0+/-15.0 minutes (mean+/-SD), respectively, were not different. Although extraction time, 34.0+/-11.0 minutes, for leads implanted for >48 months was longer than 23.0+/-16.0, 28.0+/-18.0, and 24.0+/-14.0 minutes, for leads with implant durations of 12, 24, and 48 months, respectively, such differences were not statistically significant. The extraction time, however, was directly related to the degree of fibrosis around the lead, 39.0+/-15.0 minutes for leads with severe fibrosis compared with 13.0+/-6.0 minutes for the leads with mild fibrosis (p<0.001). Patient's age, sex, or history of coronary artery bypass graft surgery did not significantly affect extraction time. All except the initial 2 lead extractions were performed in the electrophysiology laboratory. No mortality or serious complications associated with the procedure using these methods were observed.

The automated implantable cardiac defibrillator. Prophylaxis in cardiac sarcoidosis.

A patient with cardiac sarcoidosis proved by biopsy specimen and no history of sudden death or clinical sustained ventricular tachycardia prophylactically received an implantable cardioverter defibrillator (ICD) that later reversed an episode of near syncope. The patient was supported with the ICD until heart transplantation. The physiology and treatment of arrhythmias associated with cardiac sarcoidosis is described. Consideration for use of the ICD in asymptomatic patients and as bridge therapy until heart transplantation is discussed.

Early detection of acute allograft rejection by linear and nonlinear analysis of heart rate variability.

OBJECTIVE: The first months after orthotopic heart transplantation are associated with the highest risk of acute allograft rejection. This study explores the utility and reliability of linear and novel nonlinear metrics of heart rate variability as predictors of graft rejection. The underlying hypothesis is that the transplanted heart, in response to inflammatory mediators, alters the dynamic properties of its rhythm-generating system. METHODS: In a cross-sectional study of 45 patients who had undergone heart transplantation, spanning a period of 4 months after the operation, heart rate variability was examined by time- and frequency-domain analysis. The nonlinear features of heart rate variability were studied by computing a pointwise correlation dimension of R-R interval time series. The results of heart rate variability analysis were compared with those of endomyocardial surveillance biopsy studies using the International Society for Heart and Lung Transplantation scoring system. RESULTS: Duration of heart transplantation itself exhibited a significant (P<.05) association with the onset of rejection. Specific predictors of acute rejection based on heart rate variability were identified, including shortening of the R-R interval (from 700 +/- 68 to 648 +/- 72 ms), an increase in the ratio of low-frequency (0.04-0.15 Hz) to high-frequency (0.15-0.40 Hz) spectral power (from 0.3 +/- 0.2 to 0.6 +/- 0.4), and a decrease in pointwise correlation dimension values (from 1.7 +/- 0.7 to 0.9 +/- 0.3 units). Multivariable logistic regression analysis (R (2) = 0.4) revealed that the only significant independent risk predictors were pointwise correlation dimension (odds ratio, 2.2 per 0.1 unit) and duration of heart transplantation (odds ratio, 1.7 per week). CONCLUSION: Nonlinear measures of heart rate variability provide noninvasive means for identifying patients undergoing cardiac transplantation with acute rejection, thereby enabling the assessment of the time-dependent adaptive response of the donor heart to its host.

The effects of programmed ventricular stimulation on plasma procainamide levels: an experimental model.

To evaluate the effects of programmed ventricular stimulation on resultant plasma concentrations of intravenously administered procainamide, drug dosing was performed with and without ventricular stimulation on two separate days (48 hours apart) in 12 dogs (13 dosing trials) at > or = 14 days after myocardial infarction (mean: 62 days). During infarct surgery, three bipolar electrodes were plunged into left ventricular epicardium, externalized, and later used for ventricular stimulation. On the first study day, procainamide was dosed to achieve two sequential plateau plasma levels (I and II), with a 20-minute equilibrium period at each plateau before ventricular stimulation. Plasma procainamide concentrations were measured before initiation of ventricular stimulation and at the completion of ventricular stimulation for each sequential plateau level. Stimulation involved delivery of one, two, and three extrastimuli at three paced cycle lengths at three left ventricular sites before procainamide dosing and at each of the two procainamide plateau levels. Three dogs were excluded from analysis due to induction of lethal ventricular arrhythmias. No ventricular arrhythmias were induced in the remaining nine animals. On the second study day, procainamide was dosed identically, but no ventricular stimulation was performed. Intravenous drug administration and collection of plasma concentration samples were performed with +/- 1 minute on both study days. Mean plasma procainamide concentrations at the end of ventricular stimulation at dosage Levels I & II were 10% and 12% greater (P < 0.02 and P < 0.005, respectively) than plasma concentrations measured at comparable times on the study day when no ventricular stimulation was performed.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacologic therapy of ventricular tachycardia using electrophysiologic techniques.

Serial pharmacologic trials guided by electrophysiologic techniques provide an objective method for instituting effective medical therapy in patients with sustained ventricular arrhythmias. Suppression of induced ventricular tachycardia by administered antiarrhythmic agents predicts the results of chronic treatment with a high degree of accuracy. Although some controversy exists with regard to precise stimulation protocols, the ability to evaluate the advantages and potentially detrimental actions of individual drugs in a controlled environment contributes substantially to the utility of electrophysiologic testing in the selection of an optimal antiarrhythmic regimen.

Prospective evaluation of ventricular arrhythmias using electrophysiologic techniques.

Electrophysiologic testing is known to be of value both diagnostically and in the evaluation of treatment modalities for patients with recurrent sustained ventricular tachycardia, out-of-hospital cardiac arrest, and syncope of unknown etiology. Attention is being focused on the possibility of identifying patients at high risk for such lethal ventricular arrhythmias in the hope that prophylactic therapy could prevent such arrhythmias from occurring. In this article, the authors discuss the potential role of electrophysiologic testing in this prospective identification and review the current data in the two groups of patients that have been studied extensively in this regard--post-myocardial infarction patients and patients with left ventricular dysfunction and congestive heart disease. The element of study artifact is also addressed.

Extraction and replacement of permanent pacemaker leads through occluded vessels: use of extraction sheaths as conduits--balloon venoplasty as an adjunct.

Patients (pts) may present for lead extraction with symptomatic or asymptomatic subclavian vein or superior vena cava thrombosis. Replacement of permanent pacemaker leads (PPLs) in these pts may be difficult and may require accessing a new site. We examined the utility of replacing PPLs through completely occluded vessels using extraction sheaths as conduits through the total occlusion. Over six years, a total of 210 atrial and/or ventricular PPLs were extracted from 137 pts. Two pts presented with angiographically documented thrombotic occlusion of the subclavian vein. One additional pt. who had presented with a superior vena cava (SVC) syndrome, had a totally occluded innominate vein and SVC occlusion. Balloon venoplasty was used as an adjunct to dilate the SVC. In all pts, after PPLs were removed via a subclavian extraction sheath through the occluded vessel, the retained sheath was used to place a guide wire, then a peel away dilating sheath, to insert new PPLs, in each case on the side of total venous occlusion. Seven PPLs and two lead fragments were extracted, and five new PPLs replaced, ipsilateral to the venous occlusion. These data show that extraction of PPLs through thrombosed veins may be performed successfully and may not require replacing the leads through a new site. This technique spares the pt the need to access the opposite subclavian vein, and it avoids an excessive number of PPLs in the subclavian vein and SVC. The procedure illustrates an efficient means to reintroduce new PPLs with the potential to reduce associated morbidity, since repeat puncture of the subclavian vein is not required. Safety of the procedure as a whole must be considered with regard to the known risks of lead extraction, some complications of which may be substantial using current techniques.

Radiofrequency catheter ablation of atrioventricular nodal reentrant tachycardia after orthotopic heart transplantation.

Patients with orthotopic heart transplantation may develop a variety of arrhythmias. Successful radiofrequency catheter ablation for tachyarrhythmias from manifest and concealed accessory bypass tracts in transplant patients has been previously reported. We present a patient with orthotopic heart transplantation who developed typical atrioventricular nodal tachycardia, which was successfully treated by radiofrequency catheter ablation.

Effect of different location of atrial lead position on nearfield and farfield electrograms in dual chamber pacemaker-defibrillators.

The normal functioning of dual chamber pacemaker-cardioverter defibrillator (AV pacer/ICD) may be affected by oversensing of the farfield R wave (FFRW) by the atrial channel. This study aimed to investigate whether placement of the AV pacer/ICD's atrial lead at a lateral (LAT) wall location compared to a medial (MED) location i.e. the appendage of the right atrium, would reduce the amplitude of FFRWs but not the nearfield atrial electrograms (AEGMs) during sinus rhythm (SR) and ventricular fibrillation (VF). In 17 patients, real time electrograms were recorded during SR and induced VF through the atrial lead initially at the MED and subsequently at the LAT location. In 10 patients the electrograms in SR were also recorded on a computerized data acquisition and recording system at different band-pass filter settings. Although FFRWs were recorded both at MED and LAT locations, they were much smaller, 3.5+/-4.1mm during SR and 1.7+/-2.2mm during VF at the LAT location. At 30-500Hz band-pass filter, lower amplitudes of FFRWs 0.14+/-0.09 mV were recorded at the LAT location. The V/A ratios of the amplitudes of FFRWs and AEGMs were smaller at the LAT location during SR and VF. The nearfield AEGMs were of similar amplitudes at the MED and LAT locations. These data indicate that lower amplitudes of FFRWs are recorded by placement of the atrial lead at the lateral wall of the right atrium. Oversensing of FFRWs may be prevented to improve functioning of the AV pacer-ICD.

Chronic stability of bipolar epicardial plunge electrodes in dogs.

We constructed and surgically implanted 114 chronic bipolar epicardial plunge electrodes for programmed left ventricular stimulation in closed chest dogs; 88 electrodes could be analyzed in animals surviving infarct surgery. Electrode plunges were constructed of silver wire, with conduction strands of silver-plated copper wire, in medical grade silicone tubing. Electrodes were implanted epicardially through left thoracotomy and secured with prolene. Wires exited the fifth intercostal space and were tunneled subcutaneously and secured at the dorsal aspect of the neck. Baseline thresholds (mA) were recorded at a paced cycle length of 300 ms and pulse duration of 1 ms. At least 5 days after implantation, under light Nembutal sedation, thresholds were reassessed before programmed stimulation. Each lead was tested repeatedly over 5-177 (mean 28) days. The number of leads decreased with time due to animal attrition from ventricular arrhythmias. Mean pacing threshold at implantation was 0.25 mA. Mean and median threshold values reached plateau after 1 week and showed little change thereafter for the duration of the study. More than 50% of the leads maintained thresholds less than 1.5 mA through the entire study. In animals that survived, 86% of the electrodes remained useful for the duration of the protocol. These data support the use of this electrode system as effective and reliable for chronic electrophysiologic studies in dogs.

Encainide dosing in patients with severe renal dysfunction: report of a case and literature review.

Dosage of encainide for patients with lethal ventricular arrhythmias is based on pharmacodynamic effects and efficacy of arrhythmia suppression, coupled with metabolizer phenotype and extent of renal and hepatic dysfunction. Decreased clearance in patients with renal dysfunction necessitates a reduction in dosage to avoid toxic and dose-related proarrhythmic effects. This case represents a patient with severe renal dysfunction and sustained ventricular tachycardia who achieved electrophysiologically guided suppression of induced ventricular tachycardia at a steady-state encainide dose of only 25 mg daily, significantly lower than package insert or compendial recommendations for initial dosage in patients with renal insufficiency. Documented "therapeutic" metabolite concentrations correlated to electrophysiologic response. Literature review illustrates the complexity of encainide dosage in such individuals and underscores the need for therapeutic drug monitoring to individualize dosage.