Roger A. Winkle

Long-term outcome with the automatic implantable cardioverter-defibrillator

The automatic implantable cardioverter-defibrillator was implanted in 270 patients because of life-threatening arrhythmias over a 7 year period. There was a history of sustained ventricular tachycardia or fibrillation, or both, in 96% of these patients, 80% had one or more prior cardiac arrests and 78% had coronary artery disease as their underlying diagnosis. The average ejection fraction was 34%, and 96% of these patients had had an average of 3.4 antiarrhythmic drug failures per patient before defibrillator implantation. There were four perioperative deaths and eight patients had generator infection or generator erosion, or both, during the perioperative period or during long-term follow-up. Concomitant antiarrhythmic drug therapy was given to 69% of patients. Shocks from the device were given to 58% of patients. and 20% received problematic shocks. The device was removed from 16 patients during long-term follow-up for a variety of reasons. There were 7 sudden cardiac deaths and 30 nonsudden cardiac deaths, 18 of which were secondary to congestive heart failure. The actuarial incidence of sudden death, total cardiac death and total mortality from all causes was 1%, 7% and 8%, respectively, at 1 year, and 4%, 24% and 26% at 5 years. The automatic implantable cardioverter-defibrillator nearly eliminates sudden death over a long-term follow-up period in a high risk group of patients. It has an acceptable rate of complications or problems, or both, and most late deaths in these patients are nonsudden and of cardiovascular origin.

Intravenous amiodarone for recurrent sustained hypotensive ventricular tachyarrhythmias

OBJECTIVESnWe sought to determine the response rate and safety of intravenous amiodarone in patients with ventricular tachyarrhythmias refractory to standard therapies.nnnBACKGROUNDnNumerous small retrospective reports suggest a response of refractory ventricular tachyarrhythmias to intravenous amiodarone, yet no controlled prospective trials exist.nnnMETHODSnTwo hundred seventy-three patients with recurrent hypotensive ventricular tachyarrhythmias refractory to lidocaine, procainamide and bretylium were randomized to receive one of three doses of intravenous amiodarone: 525, 1,050 or 2,100 mg/24 h (mean [+/- SE] dose 743.7 +/- 418.7, 1,175.2 +/- 483.7, 1,921.2 +/- 688.8 mg, respectively) by continuous infusion over 24 h.nnnRESULTSnOf the 273 patients, 110 (40.3% response rate) survived 24 h without another hypotensive ventricular tachyarrhythmic event while being treated with intravenous amiodarone as a single agent (primary end point). A significant difference in the time to first recurrence of ventricular tachyarrhythmia (post hoc analysis) over the first 12 h was observed when the combined 1,050- and 2,100-mg dose groups were compared with the 525-mg dose group (p = 0.046). The number of supplemental (150 mg) infusions of intravenous amiodarone (given for breakthrough destabilizing tachyarrhythmias) during hours 0 to 6 (prespecified secondary end point) was significantly greater in the 525-mg dose group than in the 2,100-mg dose group (1.09 +/- 1.57 vs. 0.51 +/- 0.97, p = 0.0043). However, there was no clear dose-response relation observed in this trial with respect to success rates (primary end point), time to first recurrence of tachyarrhythmia (post hoc analysis) or mortality (secondary end point) over 24 h.nnnCONCLUSIONSnIntravenous amiodarone is a relatively safe therapy for ventricular tachyarrhythmias refractory to other medications.

Clinical pharmacology of propafenone.

We determined the efficacy, pharmacokinetics, and plasma concentration-response relationships of propafenone, a promising new antiarrhythmic drug. Thirteen patients with frequent and complex ventricular premature beats were studied after receiving four increasing doses, during drug washout and during a randomized double-blind placebo-controlled trial, to evaluate the optimal dose in each patient. A nonlinear relationship was found between propafenone dose and steady-state mean concentration with a 10-fold increase in drug concentration as dose increased threefold from 300 to 900 mg/day. There was great intersubject variability in elimination half-life (mean 6 hr, range 2.4 to 11.8), steady-state mean concentration on 900 mg/day of propafenone (mean 1008 ng/ml, range 482 to 1812), and therapeutic plasma concentration (mean 588 ng/ml, range 64 to 1044). The interaction of these three parameters in individual patients determined the duration of the antiarrhythmic action of propafenone during washout (mean ...

Effects of encainide and its metabolites on energy requirements for defibrillation.

Encainide, a class IC antiarrhythmic agent, has been associated with proarrhythmic responses of ventricular tachycardia and fibrillation requiring defibrillation in patients. We examined the short-term effects of intravenous encainide and its two major metabolites, O-demethyl-encainide (ODE) and 3-methoxy-ODE (MODE), on the energy requirements for successful defibrillation in 25 pentobarbital-anesthetized, open-chest dogs. Truncated exponential (60% tilt) defibrillation shocks were administered through right atrial spring and left ventricular epicardial patch electrodes identical to those used in man with the automatic implantable defibrillator. At baseline multiple shocks of varying energy were applied to construct curves of percent successful defibrillation as a function of energy (DF curves) for each animal. Encainide, ODE, or MODE was then infused in loading and maintenance doses to achieve QRS widening of 20% to 50%. Saline was administered to animals serving as controls. Determination of the DF curve was repeated, after which the infusion was discontinued. After 1 hr washout period, an additional DF curve was constructed. The data were analyzed by logistic regression, and the energies required for 50% successful defibrillation (E50) were compared. No significant differences existed between the four groups in body or heart weight, extent of QRS widening, or baseline E50 values. After administration of encainide and ODE, the E50 increased by 129 +/- 43% (p less than .001) and 76 +/- 34% (p less than .005), respectively. Return of E50 toward baseline was observed after the washout periods in both groups (p less than .025), demonstrating the reversibility of the drugs effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of duration of ventricular fibrillation on defibrillation efficacy in humans

The currently available automatic implantable cardioverter-defibrillator has proven highly successful for termination of ventricular tachycardia and fibrillation. Newer devices, however, permit lower energy shocks to be delivered initially and longer episodes of arrhythmia to occur before shocks are delivered. These changes may result in longer durations of arrhythmia before successful termination. Little is known about the effects of the duration of ventricular fibrillation on the efficacy of defibrillating shocks. In this study, we examined the efficacy of defibrillating shocks in 22 patients undergoing automatic implantable cardioverter-defibrillator implantation or generator change. Defibrillating shocks ranging from 300 to 600 V (5.9-24.2 J) were delivered in matched pairs after 5 and 15 seconds of ventricular fibrillation. For the 300-V shocks (5.9 J), defibrillation was accomplished in 82% of patients when the shocks were given after 5 seconds of ventricular fibrillation and in only 45% of patients when the shocks were delivered after 15 seconds (p less than 0.01). At higher energies, there was no difference in the efficacy of defibrillation shocks delivered after 5 compared with 15 seconds of ventricular fibrillation. The postshock aortic, systolic, and diastolic blood pressures were significantly lower when the shocks were given after 15 seconds of ventricular fibrillation than after only 5 seconds. We conclude that the duration of ventricular fibrillation affects defibrillation efficacy especially at energies that are relatively low compared with maximal device outputs and that longer episodes of ventricular fibrillation cause more postshock hemodynamic depression. These observations have implications for defibrillation threshold testing at the time of device implantation and for the design and programming of future automatic implantable antitachycardia devices.

Clinical experience with sotalol in patients with drug-refractory ventricular Arrhythmias

Sixty-five patients with symptomatic, drug-refractory, sustained ventricular tachycardia or fibrillation were treated with oral sotalol (80 to 480 mg twice daily). Sotalol was withdrawn in 11 patients because of continued inducibility of ventricular tachycardia at the time of follow-up electrophysiologic study. Therefore, the clinical effectiveness of sotalol could be evaluated in 54 patients followed up for 11.5 +/- 6 months (range 0.2 to 25). The actuarial incidence of successful sotalol therapy was 54 +/- 13% at 6 months and 47 +/- 13% at 12 months. In 39 patients who underwent electrophysiologic testing while receiving oral sotalol, the drug prevented the reinduction of ventricular tachycardia/fibrillation in 8 (20%). During follow-up study, arrhythmia recurred in 1 (17%) of 6 patients whose ventricular tachycardia was noninducible with oral sotalol and in 8 (44%) of 18 with inducible tachycardia but who were continued on oral sotalol therapy. Adverse effects were noted in 28 patients (42%), requiring drug withdrawal in 13 (22%) and dose reduction after hospital discharge in 10 (15%). Exacerbation of ventricular arrhythmia occurred in six patients (9%), one of whom had associated hypokalemia. Sotalol is frequently useful in the control of intractable, life-threatening ventricular arrhythmias, and its efficacy appears to be predicted by programmed stimulation. However, there is a high rate of limiting side effects, which precludes its use in a large number of patients, and a substantial risk of arrhythmia exacerbation.

First experience with a novel robotic remote catheter system: Amigo™ mapping trial

IntroductionAmigo™ (Catheter Robotics, Inc., Mount Olive, NJ) remote catheter system (RCS) was designed to provide a simple and relatively inexpensive system for remote catheter manipulation. The purpose of this study was to evaluate the performance and safety of Amigo in mapping the right side of the heart.Methods and resultsThis non-randomized, prospective clinical trial was conducted at 13 sites (NCT: #01139814). Using the controller, a mapping catheter was moved to eight pre-specified locations in a specific sequence: right ventricular apex, mid-right ventricular septum, right ventricular outflow tract, His-bundle position, coronary sinus ostium, high right atrium, lateral tricuspid annulus, and low lateral right atrium. The pre-specified efficacy endpoint was to achieve 80xa0% successful navigation to all locations. Time to each location, location accuracy, and quality of contact were confirmed by imaging and specific criteria for electrograms and pacing thresholds. In 181 patients, a total of 1,396 of 1,448 (96xa0%) locations were successfully mapped with all protocol criteria met (one-sided p valueu2009<u20090.0001). The median time to move the catheter to a new location was 24xa0s. The Amigo-related major complication rate was 0xa0% which was significantly less than the predefined endpoint of 4xa0% (one-sided pu2009=u20090.003).ConclusionWe found the Amigo RCS to be safe and effective for positioning a mapping catheter at sites within the right atrium and ventricle.

State-of-the-art of the AICD.

During the early 1980s, advances in the automatic implantable cardioverter defibrillator (AICD, CPI, St. Paul, MN, USA) were related largely to developing and improving implant techniques, making devices more reliable and more easily manufactured and in establishing widespread acceptance of the therapy. In the late 1980s, there was only modest improvement in device technology and implant technique but tbere was exponential growth of both the number of patients undergoing iniplantation and tbe number of implanting physicians. During the entire 1980s, Dr. Mirowskis personal touch was noted everywhere. He oversaw all of the early clinical trials, kept in close touch with the engineering and manufacturing aspects of tbe devices, and traveled and lectured tirelessly throughout tbe world to educate physicians about tbis lifesaving technology. At his insistence, developments related to the defibrillator were virtually always reported in peer review journals rather tban through tbe sensationalism of news releases. Obstacles large and small melted away as be followed tbe dogma of his three rules: (1) never give up, (2) never give in and (3) beat tbe bastards. In bis unselfisb way be served as a mentor belping to train a group of successors, many of wbo were initially skeptical of tbe value of tbis tecbnology. He instilled in all the same determination and entbusiasm tbat bad driven bim during tbe 20 plus years be toiled to develop this tecbnology. Wbile Micbel bad considerable knowledge of clinical arrbytbmias and defibrillation, be had little formal knowledge of clinical electropbysiology. Just as be was a great teacher and educator, be was a great listener and student. His early vision of an implanted device tbat could automatically terminate ventricular fibrillation^ rapidly evolved and expanded to include tbe multidimensional and multiprogramm-

Comparison of defibriliation efficacy in humans using a new catheter and superior vena cava spring-left ventricular patch electrodes

The automatic implantable cardioverter-defibrillator currently utilizes an electrode system that requires a major operation for implantation. Effective defibrillation using an implantable cardioverter-defibrillator catheter positioned transvenously would eliminate the morbidity associated with such surgery. Fifteen patients undergoing defibrillator implantation were studied to compare the efficacy of the catheter with that of the superior vena cava spring (6.7 cm2, anode)-left ventricular patch (13.5 cm2, cathode) electrode system using truncated exponential waveforms with 60% tilt. The catheter is 11F in diameter and tripolar. A distal platinum-iridium tip used for pacing was separated by 4 mm from a middle 4.3 cm2 platinum electrode; these were positioned at the right ventricular apex. The proximal 8.5 cm2 platinum electrode was situated at the superior vena cava-right atrial junction. Defibrillation was performed using the middle (cathode) and proximal (anode) electrodes. Ventricular fibrillation was induced by alternating current six times, and defibrillation shocks of 1, 5, 10, 15, 20 or 25 J were given in random order, first using the catheter and then the spring-patch system. Rescue shocks of higher energy were given if there was failure. Although very low energy levels appeared to be slightly more efficacious when using the spring-patch system, there was no statistically significant difference between the electrode systems for any of the energies tested. Permanent implantation of the catheter would have been suitable in 45% of the patients, as compared with 54% of patients with the spring-patch system (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term results of atrial fibrillation ablation: the importance of all initial ablation failures undergoing a repeat ablation.

BACKGROUNDnAblation is more successful for patients with paroxysmal atrial fibrillation (AF1) than for those with persistent (AF2) or longstanding persistent AF (AF3). Many patients fail initial ablation and undergo repeat ablations. Little is known about repeat ablation procedure times, complications, and outcomes.nnnMETHODSnWe evaluated Kaplan-Meier freedom from AF by AF type and sex for initial and repeat ablations and for final status of 843 patients undergoing 1122 ablations. We examined complications, procedure times and reasons why patients do not undergo repeat ablations. Cox multivariate analysis evaluated factors predicting ablation failure.nnnRESULTSnInitial ablations were more successful in AF1 than AF2 or AF3 (P < .0001) patients. For each AF type, repeat ablations were more successful than initial ablations (P = .01 to <.001). Procedure times (139.1 ± 49.1 vs 135.3 ± 45.6 minutes, P = .248) and major complications (1.66% vs 2.87%, P = .216) were similar. Women had different clinical characteristics than men, similar initial and repeat ablation success rates but lower overall success because of fewer repeat ablations (57.8% vs 68.2%, P = .047) due to patient choice (P = .028). Patients with either successful initial ablations or undergoing repeat ablations had late AF recurrence rates of 0% to 1.5% a year. Age (P = .012), larger left atria (P = .002), female sex (P = .001), AF2 (P < .0001), AF3 (P = .003), and coronary disease (P = .003) predicted failure.nnnCONCLUSIONSnRepeat ablations are more successful than initial ablations, have similar procedure times and complication rates, help determine final success rates, and may explain sex difference in success rates. For the best outcomes, patients should assume that a repeat ablation may be required to eliminate AF.