Patricia F.A. Bakker

Effect of Pacing Chamber and Atrioventricular Delay on Acute Systolic Function of Paced Patients With Congestive Heart Failure

BACKGROUND Previous studies of pacing therapy for dilated congestive heart failure (CHF) have not established the relative importance of pacing site, AV delay, and patient heterogeneity on outcome. These variables were compared by a novel technique that evaluated immediate changes in hemodynamic function during brief periods of atrial-synchronous ventricular pacing. METHODS AND RESULTS Twenty-seven CHF patients with severe left ventricular (LV) systolic dysfunction and LV conduction disorder were implanted with endocardial pacing leads in the right atrium and right ventricle (RV) and an epicardial lead on the LV and instrumented with micromanometer catheters in the LV, aorta, and RV. Patients in normal sinus rhythm were stimulated in the RV, LV, or both ventricles simultaneously (BV) at preselected AV delays in a repeating 5-paced/15-nonpaced beat sequence. Maximum LV pressure derivative (LV+dP/dt) and aortic pulse pressure (PP) changed immediately at pacing onset, increasing at a patient-specific optimal AV delay in 20 patients with wide surface QRS (180+/-22 ms) and decreasing at short AV delays in 5 patients with narrower QRS (128+/-12 ms) (P<0.0001). Overall, BV and LV pacing increased LV+dP/dt and PP more than RV pacing (P<0.01), whereas LV pacing increased LV+dP/dt more than BV pacing (P<0.01). CONCLUSIONS In this population, CHF patients with sufficiently wide surface QRS benefit from atrial-synchronous ventricular pacing, LV stimulation is required for maximum acute benefit, and the maximum benefit at any site occurs with a patient-specific AV delay.

The Pacing Therapies for Congestive Heart Failure (PATH-CHF) Study: Rationale, Design, and Endpoints of a Prospective Randomized Multicenter Study

In conjunction with pharmacologic therapy, pacing has been proposed as a potential treatment to decrease symptoms in patients with moderate-to-severe congestive heart failure (CHF). Uncontrolled studies of pacing therapy for CHF dealing with different pacing sites, modes of pacing, and atrioventricular delays have reported mixed outcomes. The Pacing Therapies in Congestive Heart Failure (PATH-CHF) study is a single-blind, randomized, crossover, controlled trial designed to evaluate the effects of pacing on acute hemodynamic function and to assess chronic clinical benefit in patients with moderate-to-severe CHF. The effect of pacing on oxygen consumption at peak exercise and at anaerobic threshold during cardiopulmonary exercise tests, and on 6-minute walk distance, have been selected as primary endpoints of the study. Secondary endpoints of the trial were changes in New York Heart Association (NYHA) functional class, quality-of-life as assessed by the Minnesota Living with Heart Failure questionnaire, and hospitalization frequency. Finally, changes in ejection fraction, cardiac output, and filling pattern were assessed by echocardiography. The trial was planned to include 53 patients from 7 centers in Europe over a period of 3 years. The study was divided into 2 parts: acute testing and chronic follow-up. The acute study, performed during the pacemaker implantation, involved extensive testing using a custom-designed computer (FLEXSTIM) and a unique burst pacing protocol (FLEXSTIM protocol) to determine the best ventricular pacing sites and the most appropriate atrioventricular delays. The chronic phase consisted of a crossover study designed to test in each patient the best univentricular pacing site and biventricular pacing as assessed by the acute hemodynamic study. The study started with the first implant in 1995 and has, to date, included 42 patients. The study is expected to be completed by the end of 1998. The results of a first interim analysis showed trends toward improvement in all primary and secondary endpoints during the pacing periods compared with no pacing.

Randomized Study of Implantable Defibrillator as First-Choice Therapy Versus Conventional Strategy in Postinfarct Sudden Death Survivors

BACKGROUND In retrospective studies of sudden cardiac death survivors, the implantable cardioverter-defibrillator (ICD) compares favorably with medical and surgical therapy. Thus, use of the conventional strategy of starting treatment with antiarrhythmic drugs (AD), at least in certain patient categories, may be questionable. The goal of this study was to analyze the effectiveness of ICD implantation as first-choice therapy versus the conventional therapeutic strategy of starting with AD. METHODS AND RESULTS Sixty consecutive survivors of cardiac arrest caused by old myocardial infarction were randomly assigned early ICD implantation (n = 29) or conventional therapy (n = 31). Baseline characteristics were similar in the two groups. Therapy in each patient was always guided by ECG monitoring, exercise testing, and programmed electrical stimulation (PES). Primary end points (main outcome events, including death, recurrent cardiac arrest, and cardiac transplantation), number of invasive procedures and antiarrhythmic therapy changes, and duration of hospitalization were compared. Median follow-up was 24 months (mean, 27 months). In the early ICD group, 4 patients (14%) died, all of cardiac causes. In the conventional group, 20 patients failed AD and subsequently underwent map-guided ventricular tachycardia (VT) surgery (6 patients) or ICD implantation (14 patients). Of the 6 VT surgery patients, 1 died, 1 had cardiac transplantation, and 1 had an ICD implantation because of persistent inducibility despite the addition of AD. Of the 11 patients who remained on AD as sole therapy, 2 died in the hospital before they could be retested by PES, leaving 9, judged adequately protected by AD alone. Of those, 5 died, and 1 survived recurrent cardiac arrest followed by ICD implantation. In total, 16 conventionally treated patients ended up with late ICD implantation, 3 of whom died. Thus, total mortality in the conventional group was 11 patients (35%): 4 died suddenly, 5 died of heart failure, and 2 died of noncardiac causes. Comparison of the main outcome events in both strategies showed a significant difference in favor of early ICD implantation (hazard ratio, 0.27; 95% CI, 0.09 to 0.85; P = .02). In addition, the early ICD group underwent fewer invasive procedures (median, 1 versus 3; P < .0001), had less therapy changes (P < .0001), and spent fewer days in hospital (median, 34 versus 49; P = .02). CONCLUSIONS These data suggest that ICD implantation as first choice is preferable to the conventional approach in survivors of cardiac arrest caused by old myocardial infarction. Conventionally treated patients are likely to end up with an ICD, and those who remain on AD as sole therapy have a high risk of death regardless of efficacy assessment, including PES.

Biventricular pacing in end-stage heart failure improves functional capacity and left ventricular function

Background Asynchronous patterns of contraction and relaxation may contribute to hemodynamic and functional impairment in heart failure. In 1993, we introduced biventricular pacing as a novel method to treat heart failure by synchronous stimulation of the right and left ventricles after an appropriate atrioventricular delay. The objectives of this study were to assess the early and long-term effects of this therapy on functional capacity and left ventricular function in patients with severe heart failure and left bundle branch block.Methods and Results Twelve patients with end-stage congestive heart failure, sinus rhythm and complete left bundle branch block were treated with biventricular stimulation at optimized atrioventricular delay. The NYHA functional class and maximal bicycle exercise capacity were assessed. Systolic and diastolic left ventricular function were studied with echocardiography and radionuclide angiography. Data was collected at various intervals during 1-year follow-up. Cumulative survival [95% CI] was 66.7% [40.0,93.4] at 1 year and 50 % [21.8, 78.2] at 2 and 3 years. Median NYHA class improved from class IV to class II at 1 year (p=0.008). After 6weeks an increase in exercise capacity occurred, which was sustained. A less restrictive left ventricular filling pattern, an increase in dP/dt and left ventricular ejection fraction, and a decrease in mitral regurgitation were observed early and long-term.Conclusions Biventricular pacing at optimized atrioventricular delay results in improvement in functional capacity, which is associated with improved systolic and diastolic left ventricular function, and a decrease in mitral regurgitation during short- and long-term follow-up.

Cost-effectiveness of Implantable Defibrillator as First-Choice Therapy Versus Electrophysiologically Guided, Tiered Strategy in Postinfarct Sudden Death Survivors A Randomized Study

BACKGROUND Rising costs of health care, partly as a result of costly therapeutic innovations, are of concern to both the medical profession and healthcare authorities. The implantable cardioverter-defibrillator (ICD) is still not remunerated by Dutch healthcare insurers. The aim of this study was to evaluate the cost-effectiveness of early implantation of the ICD in postinfarct sudden death survivors. METHODS AND RESULTS Sixty consecutive postinfarct survivors of cardiac arrest caused by ventricular tachycardia or fibrillation were randomly assigned either ICD as first choice (n = 29) or a tiered therapy starting with antiarrhythmic drugs and guided by electrophysiological (EP) testing (n = 31). Median follow-up was 729 days (range, 3 to 1675 days). Fifteen patients died, 4 in the early ICD group and 11 in the EP-guided strategy group (P = .07). For quantitative assessment, the cost-effectiveness ratio was calculated for both groups and expressed as median total costs per patient per day alive. Because effectiveness aspects other than mortality are not incorporated in this ratio, other factors related to quality of life were used as qualitative measures of cost-effectiveness. The cost-effectiveness ratios were

Unfavorable outcome in patients with primary electrical disease who survived an episode of ventricular fibrillation.

63 and

Abnormal automaticity as mechanism of atrial tachycardia in the human heart--electrophysiologic and histologic correlation: a case report

94 for the early ICD and EP-guided strategy groups, respectively, per patient per day alive. This amounts to a net cost-effectiveness of

Infections involving implanted cardioverter defibrillator devices.

11,315 per patient per year alive saved by early ICD implantation. Costs in the early ICD group were higher only during the first 3 months of follow-up, but as a result of the high proportion of therapy changes, including arrhythmia surgery and late ICD implantation, costs in the EP-guided strategy group became higher after that. Patients discharged with antiarrhythmic drugs as sole therapy had the lowest total costs. This subset, however, showed extremely high mortality, resulting in a poor cost-effectiveness ratio (

Mitral Valve Prolapse and Ventricular Arrhythmias: Observations in a Patient with a 20‐Year History

196 per day). Invasive therapies and hospitalization were the major contributors to costs. If quality-of-life measures are taken into account, the cost-effectiveness of early ICD implantation was even more favorable. Recurrent cardiac arrest and cardiac transplantation occurred in the EP-guided strategy group only, whereas exercise tolerance, total hospitalization duration, number of invasive procedures, and antiarrhythmic therapy changes were significantly in favor of early ICD implantation. CONCLUSIONS In terms of cost-effectiveness, early ICD implantation is superior to the EP-guided therapeutic strategy in postinfarct sudden death survivors.

Effects of cryothermia during cold cardioplegia on epicardial and intramural coronary arteries

BACKGROUND Prognosis in patients with ventricular tachyarrhythmia without structural heart disease (primary electrical disease) has been described as excellent. However, prognosis may be less favourable in the subgroup surviving an episode of ventricular fibrillation. METHODS AND RESULTS We prospectively followed 19 consecutive patients (age, 13 to 66 years; mean age, 33 years) who had survived an episode of documented ventricular fibrillation. Structural heart disease, preexcitation, and long QT syndromes were excluded by thorough cardiologic evaluation. All patients underwent 24-hour Holter monitoring, exercise testing, and programmed electrical stimulation according to a standardized protocol. Holter monitoring revealed episodes of ventricular tachyarrhythmia in 5 patients. Exercise testing reproducibly provoked ventricular tachycardia in 2 patients. Baseline programmed electrical stimulation yielded inducibility of rapid ventricular tachyarrhythmia in 10 patients (53%) and noninducibility in 9 (47%). Nine patients were discharged on antiarrhythmic drug therapy. A defibrillator was implanted in 10 patients. During 43-month follow-up (range, 5 to 85 months; median, 41 months), major arrhythmic events recurred in 7 patients (37%). Four of these patients had noninducibility at baseline programmed electrical stimulation. Two patients on antiarrhythmic drugs had recurrent cardiac arrest: one died suddenly and the other was successfully resuscitated from ventricular fibrillation and subsequently underwent defibrillator implantation. In the other 5 patients, termination of (pre)syncopal episodes was associated with defibrillator shocks. Termination of ventricular fibrillation was documented by Holter recording in one of these patients. Specific markers predictive of a recurrent event could not be identified, although 6 of 7 patients with recurrent events had experienced at least one episode of cardiac arrest or (pre)syncope before the index episode. CONCLUSIONS Patients with primary electrical disease presenting with ventricular fibrillation are at high risk of recurrence of major arrhythmic events during long-term follow-up. Noninducibility at baseline study does not predict an uneventful course. Also, early defibrillator implantation should be considered in these patients.