Sven Reek

Left Ventricular Lead Position and Clinical Outcome in the Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT) Trial

Background— An important determinant of successful cardiac resynchronization therapy for heart failure is the position of the left ventricular (LV) pacing lead. The aim of this study was to analyze the impact of the LV lead position on outcome in patients randomized to cardiac resynchronization-defibrillation in the Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT) study. Methods and Results— The location of the LV lead was assessed by means of coronary venograms and chest x-rays recorded at the time of device implantation. The LV lead location was classified along the short axis into an anterior, lateral, or posterior position and along the long axis into a basal, midventricular, or apical region. The primary end point of MADIT-CRT was heart failure (HF) hospitalization or death, whichever came first. The LV lead position was assessed in 799 patients, (55% patients ≥65 years of age, 26% female, 10% LV ejection fraction ⩽25%, 55% ischemic cardiomyopathy, and 71% left bundle-branch block) with a follow-up of 29±11 months. The extent of cardiac resynchronization therapy benefit was similar for leads in the anterior, lateral, or posterior position (P=0.652). The apical lead location compared with leads located in the nonapical position (basal or midventricular region) was associated with a significantly increased risk for heart failure/death (hazard ratio=1.72; 95% confidence interval, 1.09 to 2.71; P=0.019) after adjustment for the clinical covariates. The apical lead position was also associated with an increased risk for death (hazard ratio=2.91; 95% confidence interval, 1.42 to 5.97; P=0.004). Conclusion— LV leads positioned in the apical region were associated with an unfavorable outcome, suggesting that this lead location should be avoided in cardiac resynchronization therapy. Clinical Trial Registration— URL: http://clinicaltrials.gov. Unique identifier: NCT00180271.

New primary prevention trials of sudden cardiac death in patients with left ventricular dysfunction: SCD-HEFT and MADIT-II.

Primary prevention of sudden arrhythmic death in patients with organic heart disease with poor left ventricular function and/or heart failure is currently a major challenge in cardiology. Amiodarone (with or without beta blockers) and the implantable cardioverter defibrillator (ICD) are considered the 2 major therapeutic tools to prevent sudden arrhythmic death in these patients. Two large trials have been launched to define the prophylactic benefit of the ICD or amiodarone on total mortality in patients that receive optimal heart failure and anti-ischemic treatment but remain at high risk of dying suddenly. The Sudden Cardiac Death in Heart Failure Trial (SCD-Heft) is designed to determine whether amiodarone or the ICD will decrease overall mortality in patients with coronary artery disease or nonischemic cardiomyopathy who are in heart failure New York Heart Association (NYHA) class II or III and have a left ventricular ejection fraction < 35%. The primary endpoint is total mortality; secondary objectives are comparison of arrhythmic and nonarrhythmic mortality and morbidity in the 3 arms as well as quality of life, cost-effectiveness, and incidence of episodes of ventricular tachyarrhythmias. The Multicenter Automatic Defibrillator Implantation Trial (MADIT) II is a follow-up study to the MADIT trial. It examines the prophylactic benefit in coronary artery disease patients with a left ventricular ejection fraction of < 30%, who have had at least 1 myocardial infarction but require no further risk stratification. MADIT II is a sequential design trial that compares ICD versus no ICD therapy. Programmed electrical stimulation to test inducibility of ventricular tachycardia is performed during ICD implantation, and various noninvasive risk markers are tested after randomization. Primary endpoint is total mortality, and secondary objectives are quality-of-life issues as well as cost-effectiveness ratio.

A Randomized Prospective Study of Single Coil Versus Dual Coil Defibrillation in Patients with Ventricular Arrhythmias Undergoing Implantable Cardioverter Defibrillator Therapy

ICD implantation is standard therapy for malignant ventricular arrhythmias. The advantage of dual and single coil defibrillator leads in the successful conversion of arrhythmias is unclear. This study compared the effectiveness of dual versus single coil defibrillation leads. The study was a prospective, multicenter, randomized study comparing a dual with a single coil defibrillation system as part of an ICD using an active pectoral electrode. Seventy‐six patients (64 men, 12 women; age 61 ± 11 years ) were implanted with a dual (group 1, n = 38) or single coil lead system (group 2, n = 38 ). The patients represented a typical ICD cohort: 60% presented with ischemic cardiomyopathy as their primary cardiac disease, the mean left ventricular ejection fraction was 0.406 ± 0.158 . The primary tachyarrhythmia was monomorphic ventricular tachyarrhythmia in 52.6% patients and ventricular fibrillation in 38.4%. There was no significant difference in terms of P and R wave amplitudes, pacing thresholds, and lead impedance at implantation and follow‐up in the two groups. There was similarly no difference in terms of defibrillation thresholds (DFT) at implantation. Patients in group 1 had an average DFT of 10.2 ± 5.2 J compared to 10.3 ± 4.1 J in Group 2, P = NS. This study demonstrates no significant advantage of a dual coil lead system over a single coil system in terms of lead values and defibrillation thresholds. This may have important bearing on the choice of lead systems when implanting ICDs. (PACE 2003; 26:1684–1690)

Clinical Efficacy of the Wearable Cardioverter-Defibrillator in Acutely Terminating Episodes of Ventricular Fibrillation

The findings of our initial study demonstrate for the first time the ability to terminate induced VT/VF reliably (100% of all episodes) by a single, monophasic 230-J shock delivered by the Wearable Cardioverter-Defibrillator (WCD). Although limited by sample size, our data suggest the WCD could be used as a feasible bridge to definitive implantation of an implantable cardioverter-defibrillator in patients in whom risk stratification for sudden death is not completed.

Clinical efficacy of a Wearable Defibrillator in acutely terminating episodes of ventricular fibrillation using biphasic shocks

The Wearable Cardioverter Defibrillator (WCD) automatically detects and treats ventricular tachyarrhythmias without the need for assistance from a bystander, while at the same time allowing the patient to ambulate freely. It represents an alternative to emergency medical services for outpatient populations with a temporary risk of sudden cardiac death. While the original devices used a monophasic truncated exponential waveform for cardioversion/defibrillation shocks, a new, biphasic shock was developed for the next device generation. In 12 patients undergoing electrophysiological testing for ventricular tachyarrhythmias, termination of electrically induced ventricular fibrillation (VF) was attempted via the WCD. In 22 episodes, induced VF was promptly terminated by the first 70 J (n = 12) or 100 J (n = 10) biphasic shocks. Time between arrhythmia initiation and shock delivery was 22 ± 6 seconds (70 J) and 21 ± 6 seconds (100 J) (P = NS). The measured transthoracic impedance was 71 ± 5 Ω (64–79 Ω) for the 70 J shock and 64 ± 8 Ω (47–72 Ω) for the 100 J shock. The present study demonstrates that a single low energy biphasic shock delivered by the WCD, reliably terminates electrically induced VF (100% of episodes). The results of this study suggest that there is an acceptable safety margin to the maximum output of the device (150 J). Despite our promising data, we recommend that programming all shocks for maximum energy output should be done when using the WCD in ambulatory patients. (PACE 2003; 26:2016–2022)

Increased expression of P-selectin in patients with chronic atrial fibrillation.

Previous studies have shown that platelets are activated during atrial fibrillation (AF). However, prophylactic therapy with aspirin is not associated with a reduction of thromboembolic complications in patients with AF. Stimulation of platelet thrombin and ADP receptors causes a release of P‐selectin, which is not affected by aspirin. The purpose of this study was to assess the influence of AF on platelet P‐selectin expression. Blood samples from 30 patients were studied ex vivo. Nineteen patients had chronic AF (> 3 months), 11 patients were in sinus rhythm (SR). P‐selectin expression was determined by flow cytometry (antibody binding capacity [BC]) at baseline and after platelet stimulation with adenosine diphosphate (ADP) and thrombin receptor activating peptide (TRAP). To determine the effect of heart rate and atrial pressure (RAP), measurements were repeated after 10 minutes of ventricular pacing (120 beats/min) in patients with SR. P‐selectin expression was increased in patients with AF at baseline (AF: 1329 ±81 BC vs SR: 968 ± 108 BC; P < 0.05) and after stimulation with ADP (AF: 1445 ± 101 BC vs SR: 1061 ± 109 BC; P < 0.05) and TRAP (AF: 13783 ± 2442 BC vs SR: 5977 ± 800 BC; P < 0.05). RAP (2.0 ± 0.5 vs 6.0 ± 0.8 mmHg; P < 0.01) and atrial rate (75 ± 5 vs 114 ± 5 beats/min; P < 0.001) increased during ventricular pacing. However, P‐selectin levels remained stable. AF was accompanied by increased P‐selectin expression. In contrast, increased ventricular rate and elevated atrial pressure alone had no effect on platelet activity. Further studies are needed to determine if platelet ADP receptor inhibitors offer a therapeutic benefit in patients with AF.

The MUSTT Study: Evaluating Testing and Treatment

The multicenter unsustained tachycardia trial (MUSTT) tested the value of electrophysiologically guided antiarrhythmic drug therapy against no therapy in high risk coronary artery disease with poor left ventricular function (LV-EF ≤ 40%) and nonsustained ventricular tachycardia. Risk assessment was performed by testing inducibility of a sustained ventricular tachycardia. The primary endpoint of the study was sudden arrhythmic death or cardiac arrest. Significant information on risk stratification was gathered by the follow-up of patients that were noninducible. Although MUSTT was not a specific ICD trial for primary prevention of SCD the results of the trial revealed that only with ICD back-up—a significant reduction of arrhythmic death or cardiac arrest can be achieved.EP-guided antiarrhythmic drug treatment had a lower incidence of SCD/CA compared to no treatment (12% versus 25%, p = 0.043, hazard ratio 0.73 after 24 months and 18% versus 32% after 60 months). A subgroup analysis showed that the benefit of antiarrhythmic treatment was only due to ICD implantation. No difference was found between those inducible pts treated exclusively with antiarrhythmic drugs and those who were randomized to no drug treatment. Patients who were not inducible did significantly better than pts who were inducible wether or not treated with antiarrhythmic drugs.MUSTT results strengthen the data of the MADIT study. They confirm the inducibility testing as the most accurate risk stratifier. MUSST demonstrated the poor value of serial EP drug testing as well as the risk of “stand alone” antiarrhythmic drug treatment.

Inducibility of sustained ventricular tachycardia in a closed-chest ovine model of myocardial infarction.

The two goals of this study were (1) to develop a closed‐chest animal model of monomorphic ventricular tachycardia; and (2) to investigate the effect of dual site pacing on inducibility of ventricular tachycardia. In the first part of the study, 10 of 14 sheep underwent successful induction of myocardial infarction by temporary balloon occlusion of the left anterior descending coronary artery. After a follow‐up period of 21–43 days, sustained monomorphic ventricular tachycardia could be induced during programmed electrical stimulation using a “clinical” stimulation protocol in 8 of the 10 sheep. The number of ventricular tachycardia episodes per animal varied between 5 and 70. Ventricular fibrillation was never induced during programmed electrical stimulation. Ventricular tachycardia episodes lasted from 30 seconds up to 15 minutes and were terminated by antitachycardia pacing or DC cardioversion. In the second part of the study, the effect of dual site stimulation on ventricular tachycardia inducibility was investigated. High current stimuli from an area within the infarcted zone were given with the S1 programmed stimulation protocol. This dual site stimulation showed no effect on ventricular tachycardia induction during programmed electrical stimulation. This animal model shows a high induction rate of sustained monomorphic ventricular tachycardia in the chronic phase of myocardial infarction. The high incidence of ventricular tachycardia inducibility provides a reliable tool to study new techniques for the prevention of ventricular tachyarrhythmias.

Feasibility of catheter cryoablation in normal ventricular myocardium and healed myocardial infarction

Although novel cryoablation systems have recently been introduced into clinical practice for catheter ablation of supraventricular tachycardia, the feasibility of catheter cryoablation of VT is unknown. Thus, the present study evaluates catheter cryoablation of the ventricular myocardium (1) in healthy sheep and (2) of VT in chronic myocardial infarction (MI). In three healthy sheep, 21 ventricular lesions (12 left and 9 right ventricle) were created with a catheter cryoablation system. Different freeze/thaw characteristics were used for lesion creation. The mean nadir temperature was ‐84.1°C ± 0.9°C, mean lesion volume was 175.8 ± 170.3 mm3, and 5 of 21 lesions were transmural. Lesion dimensions were 7.5 ± 3.1 mm (width) and 4.2 ± 2.5 mm (depth). Left ventricular lesions were significantly larger than right ventricular lesions (262 ± 166 vs 60.5 ± 91.6 mm3, P = 0.0025). There was no difference in lesion volume with respect to different freeze/thaw characteristics. Anatomically (n = 3) or electrophysiologically (n = 3) guided catheter cryoablation was attempted in six sheep 105 ± 56 days after MI, three of six animals had reproducibly inducible VT with a mean cycle length of 215 ± 34 ms prior to ablation. In these animals, five VTs were targeted for ablation. A mean of 6 ± 3 applications for nine left ventricular lesions were applied, six of nine lesions were transmural. The mean lesion volume was 501 ± 424 mm3. No VT was inducible in two of three animals after cryoablation using an identical stimulation protocol. Therefore, catheter cryoablation of VT in healed MI is feasible, and no acute complications were observed.

Noncontact Mapping of Ventricular Tachycardia in a Closed‐Chest Animal Model of Chronic Myocardial Infarction

Treatment of ventricular tachyarrhythmias in the setting of chronic myocardial infarction requires accurate characterization of the arrhythmia substrate. New mapping technologies have been developed that facilitate identification and ablation of critical areas even in rapid, hemodynamically unstable ventricular tachycardia.