Electrogram morphology discriminators in implantable cardioverter defibrillators: A comparative evaluation.

BACKGROUND: Morphology algorithms are currently recommended as a standalone discriminator in single-chamber implantable cardioverter defibrillators (ICDs). However, these proprietary algorithms differ in both design and nominal programming. OBJECTIVE: To compare three different algorithms with nominal versus advanced programming in their ability to discriminate between ventricular (VT) and supraventricular tachycardia (SVT). METHODS: In nine European centers, VT and SVTs were collected from Abbott, Boston Scientific, and Medtronic dual- and triple-chamber ICDs via their respective remote monitoring portals. Percentage morphology matches were recorded for selected episodes which were classified as VT or SVT by means of atrioventricular comparison. The sensitivity and related specificity of each manufacturer discriminator was determined at various values of template match percentage from receiving operating characteristics (ROC) curve analysis. RESULTS: A total of 534 episodes were retained for the analysis. In ROC analyses, Abbott Far Field MD (area under the curve [AUC]: 0.91; P < .001) and Boston Scientific RhythmID (AUC: 0.95; P < .001) show higher AUC than Medtronic Wavelet (AUC: 0.81; P < .001) when tested for their ability to discriminate VT from SVT. At nominal % match threshold all devices provided high sensitivity in VT identification, (91%, 100%, and 90%, respectively, for Abbott, Boston Scientific, and Medtronic) but contrasted specificities in SVT discrimination (85%, 41%, and 62%, respectively). Abbott and Medtronic's nominal thresholds were similar to the optimal thresholds. Optimization of the % match threshold improved the Boston Scientific specificity to 79% without compromising the sensitivity. CONCLUSION: Proprietary morphology discriminators show important differences in their ability to discriminate SVT. How much this impact the overall discrimination process remains to be investigated.

Assessment of cardiac resynchronisation therapy in patients with wide QRS and non-specific intraventricular conduction delay: rationale and design of the multicentre randomised NICD-CRT study.

INTRODUCTION: Cardiac resynchronisation therapy (CRT) was initially developed to treat patients with left bundle branch block (LBBB). However, many patients with heart failure have a widened QRS but neither left-BBB nor right-BBB; this is called non-specific intraventricular conduction delay (NICD). It is unclear whether CRT is effective in this subgroup of patients. METHODS AND ANALYSIS: The NICD-CRT study is a prospective, double-blind, randomised (1:1), parallel-arm, multicentre trial comparing the effects of CRT in patients with heart failure, a reduced left ventricular ejection fraction (LVEF <35%) and NICD, who have been implanted with a device (CRT-pacemaker or CRT-defibrillator) that has or has not been activated. Enrolment began on 15 July 2015 and should finish within 3 years; 40 patients have already been randomised and 11 centres have agreed to participate. The primary end point is the comparison of the proportion of patients improved, unchanged or worsened over the subsequent 12 months. 100 patients per group are required to demonstrate a difference between groups with a statistical power of 90%, a type I error of 0.05% (two-sided) and a loss to follow-up of 10%. This trial will add substantially to the modest amount of existing data on CRT in patients with NICD and should reduce uncertainty for guidelines and clinical practice when added to the pool of current information. ETHICS AND DISSEMINATION: Local ethics committee authorisations have been obtained since May 2015. We will publish findings from this study in a peer-reviewed scientific journal and present results at national and international conferences. TRIAL REGISTRATION NUMBER: NCT02454439; pre-results.

Role of patient education in the perception and acceptance of home monitoring after recent implantation of cardioverter defibrillators: the EDUCAT study.

BACKGROUND: Much attention is being paid to the education of and provision of medical information to patients, to optimize their understanding and acceptance of their disease. AIMS: To ascertain the impact of educating recent recipients of an implantable cardioverter defibrillator (ICD) on their perception and acceptance of a home monitoring (HM) system. METHODS: Questionnaire 1, completed one month after ICD implantation, was designed to assess: the quality of patient preparation for HM; patient comprehension of HM; and patient anxiety experienced during its installation. The comprehension questions were assigned a score of -2 for an incorrect answer, +1 for a correct answer and 0 for neither (total score ranging from -40 to +20). Questionnaire 2, completed six months after ICD implantation, assessed patient acceptance of and anxiety about HM. RESULTS: The registry included 571 patients (mean age 63.9±12.8 years; 83% men; 76% of ICDs implanted for primary prevention) followed by HM for 6.2±1.2 months. Questionnaire 1 was completed by 430 (75.3%) patients and questionnaire 2 by 398 (69.7%) patients. Younger patients had a better comprehension of HM than older patients. High-quality training conditions improved the comprehension score, and a positive association was observed between anxiety and acceptance levels and the comprehension score. The 80±20% mean data transmission rate (days of transmission/days of follow-up ratio) was unrelated to the comprehension scores. CONCLUSION: A clear understanding was associated with a higher acceptance of HM, although it was unrelated to the data transmission rate.

Impact of pacing site on QRS duration and its relationship to hemodynamic response in cardiac resynchronization therapy for congestive heart failure.

INTRODUCTION: Recent studies have demonstrated that left ventricular (LV) pacing site is a critical parameter in optimizing cardiac resynchronization therapy (CRT). The present study evaluates the effect of pacing from different LV locations on QRS duration (QRSd) and their relationship to acute hemodynamic response in congestive heart failure patients. METHODS AND RESULTS: Thirty-five patients with nonischemic dilated cardiomyopathy and left bundle branch block referred for CRT device implantation were studied. Eleven predetermined LV pacing sites were systematically assessed in random order: epicardial: coronary sinus (CS); endocardial: basal and mid-cavity (septal, anterior, lateral, and inferior), apex, and the endocardial site facing the CS pacing site. For each patient QRSd and +dP/dtmax during baseline (AAI) and DDD LV pacing at 2 atrioventricular delays were compared. Response to CRT was significantly better in patients with wider baseline QRSd (≥150 milliseconds). Hemodynamic response was inversely correlated to increase of QRSd during LV pacing (short atrioventricular [AV] delay: r = 0.44, P < 0.001; long AV delay: r = 0.59, P < 0.001). Compared to baseline, LV pacing at the site of shortest QRSd significantly improved +dP/dtmax (+18 ± 25%, P < 0.001) but was not superior to other conventional strategy (lateral wall, CS pacing, and echo-guided) and was inferior to a hemodynamically guided strategy. CONCLUSIONS: In our study, we have demonstrated that changes of QRSd during LV pacing correlated with acute hemodynamic response and that LV pacing location was a primary determinant of paced QRSd. Although QRSd did not predict the maximum hemodynamic response, our results confirm the link between electrical activation and hemodynamic response of the LV during CRT.

Contributions of a hemodynamic sensor embedded in an atrial lead in a porcine model.

INTRODUCTION: Preliminary studies have revealed a high correlation between peak endocardial acceleration (PEA) measured with a sensor embedded in a ventricular lead and human cardiac contractility. In this study we assessed (1) the contributions made by measurements of PEA1, an index of ventricular systolic contraction, from the right atrium, and (2) the feasibility of recording a fourth component of PEA (PEA4), coincident with atrial contraction and corresponding to the phonocardiographic fourth heart sound. METHODS: We placed a PEA sensor embedded at the tip of a right atrial lead in 9 pigs. A 7F Millar catheter tip micromanometer was introduced into the left ventricular (LV) cavity to measure dP/dt(max). Myocardial contractility was increased by infusion of dobutamine and depressed by the infusion of esmolol. We searched, during VDD pacing, for PEA4 following atrial systole, while gradually lengthening the atrioventricular delay. Ventricular fibrillation was then triggered by rapid stimulation. RESULTS: The changes in PEA1 were correlated with the changes in LV dP/dt(max) (r = 0.91; P < 0.001). A low-frequency component of the endocardial signal (PEA4) was visible approximately 50 milliseconds after the atrial electrogram in all experiments. Following the induction of ventricular fibrillation, PEA4 remained visible on the endocardial recording, simultaneous with the sensed atrial electrogram. CONCLUSIONS: This study confirms the merit of embedding a PEA sensor in an atrial lead. The exploitation of the information provided by the PEA1 signal remains pertinent and the possibility to record an additional PEA4 component offers the perspective of new clinical applications.

Left ventricular endocardial stimulation for severe heart failure.

Biventricular resynchronization, a therapy recommended for patients presenting with left ventricular (LV) dysfunction and ventricular dyssynchrony, requires the implantation of an LV lead, usually placed in a lateral or posterolateral tributary of the coronary sinus. Despite important progress made in the development of dedicated instrumentation, the procedure remains sometimes challenging and unsuccessful in a minority of patients. In the rare instances of unsuccessful transvenous implantations occurring in the presence of major surgical contraindications, a few operators have implanted the LV lead transseptally, an approach limited by technical difficulties and by the thromboembolic risk associated with the presence of a lead inside the LV cavity. The interest in this approach was recently renewed by 2 studies in an animal model and in humans, respectively, which both found a distinctly superior hemodynamic performance associated with endocardial compared with epicardial stimulation. This review discusses the advantages and disadvantages of LV endocardial stimulation, examines the various techniques of LV endocardial stimulation, and projects their future applications in light of these highly promising recent results. The implementation of endocardial stimulation will ultimately depend on: 1) the development of safe, effective, and durable instrumentation, and reliable and reproducible intraprocedural methods to identify the optimal site of stimulation; and 2) the completion of controlled trials confirming the superiority of this technique compared with standard cardiac resynchronization therapy.

Addition of a second LV pacing site in CRT nonresponders rationale and design of the multicenter randomized V(3) trial.

BACKGROUND: Cardiac resynchronization therapy (CRT) is an effective treatment of heart failure (HF) in presence of a depressed left ventricular (LV) ejection fraction and a wide QRS complex. It is limited by a high proportion of nonresponders. Attempts have been made, in small studies, to increase the number of stimulation sites to optimize the resynchronization therapy. V(3) is a planned multicenter, randomized trial whose objective is to evaluate the clinical benefit conferred by the addition of a second LV lead in nonresponders after at least 6 months of standard biventricular stimulation. METHODS AND RESULTS: A total of 84 patients will be enrolled in 11 French medical centers. Patients will be randomly assigned to receive either an additional LV lead (test group) or to keep their current stimulation system unchanged (control group). Enrollment is planned to begin in March 2010 and is expected to end within 1 year. The primary study end point will be the HF clinical composite score evaluated at 1 year follow-up. Secondary end points include degree of echocardiographic reverse remodeling and changes in clinical measurements. CONCLUSIONS: The V(3) trial will examine the clinical benefit conferred by the addition of a second LV lead in nonresponders to standard CRT.

Extraction of old pacemaker or cardioverter-defibrillator leads by laser sheath versus femoral approach.

BACKGROUND: Some operators routinely extract chronically implanted transvenous leads from a femoral, whereas others prefer a superior approach. This prospective study compared the safety and effectiveness of laser sheaths versus femoral snare extractions. METHODS AND RESULTS: The single-center study comprised 101 patients referred for unequivocal indications to extract > or =1 transvenous lead(s). Patients were >4 years of age and were randomly assigned to extractions with a laser sheath (group 1: n=50) versus a snare via femoral approach (group 2: n=51). The multicenter study comprised 358 patients who underwent extraction of old transvenous leads using laser sheaths (n=218, group 3) in 3 centers and from a femoral approach (n=138, group 4) in 3 other centers. In the single-center study, the success and complications rates were similar in groups 1 and 2. No patient died of a periprocedural complication. The procedural duration (51+/-22 versus 86+/-51 minutes) and duration of total fluoroscopic exposure (7+/-7 versus 21+/-17 minutes) were significantly shorter (each P<0.01) in group I than in group 2. In the multicenter study, we observed 2 procedure-associated deaths in group 3 versus 1 in group 4. Major procedural complications were observed in 3% of patients in group 3, versus 3% in group 4 (P=NS). The rates of complete, partial, and unsuccessful extractions were similar in groups 3 and 4. CONCLUSIONS: Old transvenous leads were extracted with similar success and complication rates by the femoral and laser approaches. However, the femoral approach was associated with longer procedures and a longer duration of fluoroscopic exposure.

Optimizing hemodynamics in heart failure patients by systematic screening of left ventricular pacing sites: the lateral left ventricular wall and the coronary sinus are rarely the best sites.

OBJECTIVES: We sought to evaluate the impact of the left ventricular (LV) pacing site on hemodynamic response to cardiac resynchronization therapy (CRT). BACKGROUND: CRT reduces morbidity and mortality in heart failure patients. However, 20% to 40% of eligible patients may not fully benefit from CRT device implantation. We hypothesized that selecting the optimal LV pacing site could be critical in this issue. METHODS: Thirty-five patients with nonischemic dilated cardiomyopathy referred for CRT device implantation were studied. Intraventricular dyssynchrony and latest activated LV wall were defined by tissue Doppler imaging analysis before the study. Eleven predetermined LV pacing sites were systematically assessed in random order: basal and mid-cavity (septal, anterior, lateral, inferior), apex, coronary sinus (CS), and the endocardial site facing the CS pacing site. For each patient, +dP/dT(max), -dP/dT(min), pulse pressure, and end-systolic pressure during baseline (AAI) and DDD LV pacing were compared. Two atrioventricular delays were tested. RESULTS: Major interindividual and intraindividual variations of hemodynamic response depending on the LV pacing site were observed. Compared with baseline, LV DDD pacing at the best LV position significantly improved +dP/dT(max) (+31 +/- 26%, p < 0.001) and was superior to pacing the CS (+15 +/- 23%, p < 0.001), the lateral LV wall (+18 +/- 22%, p < 0.001), or the latest activated LV wall (+11 +/- 17%, p < 0.001). CONCLUSIONS: The pacing site is a primary determinant of the hemodynamic response to LV pacing in patients with nonischemic dilated cardiomyopathy. Pacing at the best LV site is associated acutely with fewer nonresponders and twice the improvement in +dP/dT(max) observed with CS pacing.

Electrocardiogram-based algorithm to predict the left ventricular lead position in recipients of cardiac resynchronization systems.

INTRODUCTION: Biventricular pacing is associated with various electrocardiographic patterns depending on the position of the left ventricular (LV) lead. We aimed to develop an electrocardiogram-based algorithm to predict the position of the LV lead. METHODS: The algorithm was developed in 100 consecutive recipients of cardiac resynchronization therapy (CRT) systems. QRS axis, morphology, and polarity were analyzed with a view to define the specific electrocardiographic characteristics associated with the various LV lead positions. The algorithm was prospectively validated in 50 consecutive CRT device recipients. RESULTS: The first analysis of the algorithm was the QRS morphology in V(1). A positive R wave in V(1) suggested LV lateral or posterior wall stimulation. A QS pattern was specific of anterior LV leads. In the presence of an R wave in V(1), V(6) was analyzed to distinguish between an inferior and anterior LV lead. Inferior leads were never associated with a positive V(6). To differentiate between lateral and posterior positions, we analyzed the pattern in V(2). Lateral leads were associated with an R morphology in V(1) and a negative V(2). Posterior leads were associated with an R morphology in V(1) and V(2). The algorithm allowed a reliable distinction between an inferior or anterior and a lateral or posterior lead position in 90% of patients. Inferior, anterior, lateral, and posterior positions were reliably distinguished in 80% of patients. CONCLUSION: This algorithm predicted the position of the LV lead with a high sensitivity and predictive value.

Predictors of a positive response to biventricular pacing in patients with severe heart failure and ventricular conduction delay.

BACKGROUND: Cardiac resynchronization therapy (CRT) is recommended in patients with ejection fraction <35%, QRS width> 120 ms, and New York Heart Association (NYHA) functional class III or IV despite optimal medical therapy. We aimed to define demographic, clinical, and electrocardiographic predictors of positive clinical response to CRT. METHODS AND RESULTS: Hundred consecutive patients fulfilling the recommended criteria were implanted with a CRT device. Demographic, clinical, two-dimensional echocardiographic and electrographic parameters were measured at baseline and after 6 months of simultaneous biventricular pacing. A positive response to CRT included an improvement of at least one NYHA functional class associated with an absence of hospitalization for worsening heart failure. At the end of follow-up, 12 patients were dead and 71% of the patients were classified as responders. After 6 months of CRT, the ejection fraction was significantly higher (P = 0.035) in responders versus nonresponders. Multivariate analysis identified three independent predictors of positive response to CRT: an idiopathic origin of the cardiomyopathy (P = 0.043), a wider QRS before implantation (P = 0.017), and a narrowing of the QRS after implantation (P = 0.037). CONCLUSION: An idiopathic origin of the cardiomyopathy, a wider QRS before implantation, and a narrowing of the QRS width after implantation were identified as independent predictors of clinical positive response to CRT.

High prevalence of sleep apnea syndrome in patients with long-term pacing: the European Multicenter Polysomnographic Study.

BACKGROUND: Cardiovascular diseases leading to pacemaker implantations are suspected of being associated with a high rate of undiagnosed sleep apnea syndrome (SAS). We sought to determine the prevalence and consequences of SAS in pacemaker patients according to pacing indications: heart failure, symptomatic diurnal bradycardia, and atrioventricular block. METHODS AND RESULTS: Ninety-eight consecutive patients (mean age, 64+/-8 years) not known to have sleep apnea were included; 29 patients were paced for dilated cardiomyopathy (29%), 33 for high-degree atrioventricular block (34%), and 36 for sinus node disease (37%). All underwent Epworth Sleepiness Scale assessment and polysomnography with the pacemaker programmed to right ventricular DDI pacing mode (lower pacing rate, 50 pulses per minute). SAS was defined as an apnea-hypopnea index > or = 10/h. Mean Epworth Sleepiness Scale was in the normal range (7+/-4), although 13 patients (25%) had an abnormal score > 11/h. Fifty-seven patients (59%) had SAS; of these, 21 (21.4%) had a severe SAS (apnea-hypopnea index > 30/h). In patients with heart failure, 50% presented with SAS (mean apnea-hypopnea index, 11+/-7) compared with 68% of patients with atrioventricular block (mean apnea-hypopnea index, 24+/-29) and 58% with sinus node disease (mean apnea-hypopnea index, 19+/-23). CONCLUSIONS: In paced patients, there is an excessively high prevalence of undiagnosed SAS (59%). Whether treating SAS would have changed the need for pacing is unknown. Treatment effects should be further evaluated particularly because these patients are less symptomatic than typical SAS patients. In any case, SAS should be systematically searched for in paced patients owing to potential detrimental effects on their cardiovascular evolution.

Outcome after implantation of a cardioverter-defibrillator in patients with Brugada syndrome: a multicenter study.

BACKGROUND: Brugada syndrome is an arrhythmogenic disease characterized by an increased risk of sudden cardiac death (SCD) by ventricular fibrillation. At present, an implantable cardioverter-defibrillator (ICD) is the recommended therapy in high-risk patients. This multicenter study reports the outcome of a large series of patients implanted with an ICD for Brugada syndrome. METHODS AND RESULTS: All patients (n=220, 46+/-12 years, 183 male) with a type 1 Brugada ECG pattern implanted with an ICD in 14 centers between 1993 and 2005 were investigated. ICD indication was based on resuscitated SCD (18 patients, 8%), syncope (88 patients, 40%), or positive electrophysiological study in asymptomatic patients (99 patients, 45%). The remaining 15 patients received an ICD because of a family history of SCD or nonsustained ventricular arrhythmia. During a mean follow-up of 38+/-27 months, no patient died and 18 patients (8%) had appropriate device therapy (10+/-15 shocks/patient, 26+/-33 months after implantation). The complication rate was 28%, including inappropriate shocks, which occurred in 45 patients (20%, 4+/-3 shocks/patient, 21+/-20 months after implantation). The reasons for inappropriate therapy were lead failure (19 patients), T-wave oversensing (10 patients), sinus tachycardia (10 patients), and supraventricular tachycardia (9 patients). Among implantation parameters, high defibrillation threshold, high pacing threshold, and low R-wave amplitude occurred, respectively, in 12%, 27%, and 15% of cases. CONCLUSIONS: In this large Brugada syndrome population, a low incidence of arrhythmic events was found, with an annual event rate of 2.6% during a follow-up of >3 years, in addition to a significant risk of device-related complications (8.9%/year). Inappropriate shocks were 2.5 times more frequent than appropriate ones.

Dynamic ventricular dyssynchrony: an exercise-echocardiography study.

OBJECTIVES: We sought to assess the effects of exercise on ventricular dyssynchrony in patients with normal and depressed left ventricular (LV) function. BACKGROUND: Asynchronous myocardial contraction adversely influences ventricular function and is associated with a poor prognosis in heart failure. Exercise-induced changes in ventricular dyssynchrony may be an important determinant of dynamic changes in cardiac output and mitral regurgitation. METHODS: A total of 65 consecutive heart failure patients and 50 matched healthy control patients underwent exercise echocardiography. Conventional and tissue Doppler parameters were measured before and during symptom-limited exercise. Left ventricular dyssynchrony was defined as the standard deviation of 12 LV segmental electromechanical delays. Analysis of the control group allowed delimitation of normal cutoff values. RESULTS: In patients with normal left ventricular function, exercise did not modify the extent of LV asynchrony. In contrast, in heart failure patients, LV dyssynchrony increased by at least 20% in 34%, remained stable in 37%, and decreased by at least 20% in 29%. Moreover, 26% of heart failure patients had either exercise induction or normalization of ventricular dyssynchrony. A significant association was found between exercise-induced changes in dyssynchrony and the presence of ischemic cardiomyopathy (p < 0.05). Rest-exercise differences in ventricular dyssynchrony were correlated with changes in cardiac output and mitral regurgitation (r = -0.63 and 0.56, respectively). CONCLUSIONS: In heart failure patients, exercise can alter the magnitude of ventricular dyssynchrony. Some patients have a response to exertion with induction of ventricular dyssynchrony, whereas others show normalization. Changes in ventricular dyssynchrony during exercise correlate with alterations in cardiac output and mitral regurgitation.

Cardiovascular effects and risk of syncope related to donepezil in patients with Alzheimer's disease.

BACKGROUND: When otherwise unexplained, syncope in patients with Alzheimer's disease may be attributed to bradycardia caused by cholinesterase inhibitors. We studied prospectively the clinical events and cardiovascular changes occurring during treatment with donepezil in patients with Alzheimer's disease. METHODS: Consecutive patients presenting with mild-to-moderate Alzheimer's disease were included in the study. Their clinical characteristics, blood pressure, heart rate and electrocardiogram were recorded before (baseline) and during treatment with donepezil. The drug was administered at a dosage of 5 mg/day for 1 month and 10 mg/day for the following 7 months, as tolerated. We compared the baseline observations with those made at 1, 2 and 8 months of donepezil treatment. We also examined the effects of negatively chronotropic or dromotropic drugs concomitantly administered with donepezil. RESULTS: Thirty patients were included in the study, of whom 43% were taking negatively chronotropic or dromotropic drugs. The first month of therapy (donepezil 5 mg/day) was completed by 26 patients. During the 7-month high-dosage phase (10 mg/day), four patients dropped out of the study; thus, 22 patients completed the full 8 months of the study. The mean heart rate was 66 +/- 8 beats/min at baseline in the overall study population. This decreased significantly to 62 +/- 9, 61 +/- 7 and 62 +/- 8 beats/min at the 1, 2 and 8 month timepoints, respectively (all p = 0.002 vs baseline). Among patients not receiving negatively chronotropic or dromotropic drugs, heart rate decreased significantly over the course of the study (from 67 +/- 8 beats/min at baseline to 62 +/- 8 beats/min at 1 month, 62 +/- 7 beats/min at 2 months and 62 +/- 8 beats/min at 8 months [all p = 0.005 vs baseline]). There was no significant change in heart rate in patients who were receiving negatively chronotropic or dromotropic drugs. The PR interval increased over the course of the study in all patient groups, but these changes were only statistically significant in the group of patients who were not taking negatively chronotropic or dromotropic drugs (155 +/- 23ms at baseline vs 158 +/- 21, 160 +/- 22 and 163 +/- 24ms at the 1, 2 and 8 month timepoints; all p = 0.02 vs baseline). One patient developed syncope due to orthostatic hypotension; there were no cases of bradycardia-induced syncope. Gastrointestinal manifestations were reported in ten of the study patients. Abdominal pain and vomiting were the reasons for study termination in five of the eight patients who did not complete the trial. CONCLUSION: A donepezil-induced decrease in heart rate and increase in PR interval were observed only in patients with Alzheimer's disease who were not treated with negatively chronotropic or dromotropic drugs. These changes were not associated with bradycardia-induced syncope.

Echocardiographic assessment during exercise of heart failure patients with cardiac resynchronization therapy.

This prospective echocardiographic study investigated the respective impacts of left ventricular (LV) pacing and simultaneous and sequential biventricular pacing (BVP) on ventricular dyssynchrony during exercise in 23 patients with compensated heart failure and ventricular conduction delays. During exercise, LV pacing and BVP significantly (p <0.05) improved mitral regurgitation and LV dyssynchrony compared with spontaneous activation. LV segmental electromechanical delays were significantly prolonged during LV pacing, leading to increased systolic time (p <0.05), decreased LV filling time (p <0.05), and decreased stroke volume (p <0.05) compared with BVP. After optimization of the interventricular delay with sequential BVP, additional benefit was obtained during exercise in terms of stroke volume and mitral regurgitation (p <0.05). The optimal interventricular delay was different at rest and during exercise in 57% of the patients. Changes from at rest to exercise in LV dyssynchrony were correlated with changes in stroke volume (r = -0.61, p <0.01) and changes in mitral regurgitation (r = 0.60, p <0.01).

Cardiac resynchronization therapy: Part 1--issues before device implantation.

Cardiac resynchronization therapy (CRT) has been used extensively over the last years in the therapeutic management of patients with end-stage heart failure. Data from 4,017 patients have been published in eight large, randomized trials on CRT. Improvement in clinical end points (symptoms, exercise capacity, quality of life) and echocardiographic end points (systolic function, left ventricular size, mitral regurgitation) have been reported after CRT, with a reduction in hospitalizations for decompensated heart failure and an improvement in survival. However, individual results vary, and 20% to 30% of patients do not respond to CRT. At present, the selection criteria include severe heart failure (New York Heart Association functional class III or IV), left ventricular ejection fraction <35%, and wide QRS complex (>120 ms). Assessment of inter- and particularly intraventricular dyssynchrony as provided by echocardiography (predominantly tissue Doppler imaging techniques) may allow improved identification of potential responders to CRT. In this review a summary of the clinical and echocardiographic results of the large, randomized trials is provided, followed by an extensive overview on the currently available echocardiographic techniques for assessment of LV dyssynchrony. In addition, the value of LV scar tissue and venous anatomy for the selection of potential candidates for CRT are discussed.

Cardiac resynchronization therapy: Part 2--issues during and after device implantation and unresolved questions.

Encouraged by the clinical success of cardiac resynchronization therapy (CRT), the implantation rate has increased exponentially, although several limitations and unresolved issues of CRT have been identified. This review concerns issues that are encountered during implantation of CRT devices, including the role of electroanatomical mapping, whether CRT implantation should be accompanied by simultaneous atrioventricular nodal ablation in patients with atrial fibrillation, procedural complications, and when to consider surgical left ventricular lead positioning. Furthermore, (echocardiographic) CRT optimization and assessment of CRT benefits after implantation are highlighted. Also, controversial issues such as the potential value of CRT in patients with mild heart failure or narrow QRS complex are addressed. Finally, open questions concerning when to combine CRT with implantable cardioverter-defibrillator therapy and the cost-effectiveness of CRT are discussed.

Causes of syncope in patients with Alzheimer's disease treated with donepezil.

INTRODUCTION: Treatment of Alzheimer's disease (AD) with cholinesterase inhibitors carries a theoretical risk of precipitating bradycardia. Though syncope occurs in patients with AD, its aetiology is unclear. The aim of this study was to determine the causes of syncope in patients with AD who were treated with donepezil and hospitalised for evaluation of syncope. METHODS: We studied 16 consecutive patients (12 women, 4 men) with AD aged 80 +/- 4 years who were hospitalised for evaluation of syncope. All patients underwent staged evaluation, ranging from physical examination to electrophysiological testing. RESULTS: The mean dose of donepezil administered was 7.8 mg/day, and the mean duration of donepezil treatment at the time of syncope was 12 +/- 8 months. A cause of syncope was identified in 69% of patients. Carotid sinus syndrome was observed in three patients, complete atrioventricular block in two patients, sinus node dysfunction in two patients, severe orthostatic hypotension in two patients and paroxysmal atrial fibrillation in one patient. A brain tumour was discovered in one patient. No cause of syncope was found in 31% of patients despite comprehensive investigation. Repetition of the investigations after discontinuation of donepezil was noncontributory. CONCLUSION: In patients with AD treated with donepezil, a noninvasive evaluation identified a probable cause of syncope in over two-thirds of patients. Cardiovascular abnormalities were predominant. Noninvasive evaluation is recommended before discontinuing treatment with cholinesterase inhibitors in patients with AD and unexplained syncope.

Spectral analysis identifies sites of high-frequency activity maintaining atrial fibrillation in humans.

BACKGROUND: The identification of sites of dominant activation frequency during atrial fibrillation (AF) in humans and the effect of ablation at these sites have not been reported. METHODS AND RESULTS: Thirty-two patients undergoing AF ablation (19 paroxysmal, 13 permanent) during ongoing arrhythmia were studied. Electroanatomic mapping was performed, acquiring 126+/-13 points per patient throughout both atria and coronary sinus. At each point, 5-second electrograms were obtained to determine the highest-amplitude frequency on spectral analysis and to construct 3D dominant frequency (DF) maps. The temporal stability of the recording interval was confirmed in a subset. Ablation was performed with the operator blinded to the DF maps. The effect of ablation at sites with or without high-frequency DF sites (maximal frequencies surrounded by a decreasing frequency gradient > or =20%) was evaluated by determining the change in AF cycle length (AFCL) and the termination and inducibility of AF. The spatial distribution of the DF sites was different in patients with paroxysmal and permanent AF; paroxysmal AF patients were more likely to harbor the DF site within the pulmonary vein, whereas in permanent AF, atrial DF sites were more prevalent. Ablation at a DF site resulted in significant prolongation of the AFCL (180+/-30 to 198+/-40 ms; P<0.0001; kappa=0.77), whereas in the absence of a DF site, there was no change in AFCL (169+/-22 to 170+/-22 ms; P=0.4). AF terminated during ablation in 17 of 19 patients with paroxysmal and 0 of 13 with permanent AF (P<0.0001). When 2 patients with nonsustained AF during mapping were excluded, 13 of 15 (87%) had AF termination at DF sites (54% at the initially ablated DF site): 11 pulmonary veins and 2 atrial. In addition, AF could no longer be induced in 69% with termination of AF at a DF site. There were no significant differences in the number or percentage of DF sites detected (5.4+/-1.6 versus 4.9+/-2.1; P=0.3) and ablated (1.9+/-1.0 versus 2.4+/-1.0; P=0.3) in those with and without AF termination. The duration of radiofrequency ablation to achieve termination was significantly shorter than that delivered in those with persisting AF (34.8+/-24.0 versus 73.5+/-22.9 minutes; P=0.0002). All patients with persisting AF had additional DF sites outside the ablated zones. CONCLUSIONS: Spectral analysis and frequency mapping identify localized sites of high-frequency activity during AF in humans with different distributions in paroxysmal and permanent AF. Ablation at these sites results in prolongation of the AFCL and termination of paroxysmal AF, indicating their role in the maintenance of AF.