Cardiac Resynchronization Therapy Pacemaker Research Articles

FDA’S Perspectives on Cardiovascular Devices

The Food and Drug Administration (FDA) decision process for approving or clearing medical devices is often determined by a review of robust clinical data and extensive preclinical testing of the device. The mission statement for the Center for Devices and Radiological Health (CDRH) is to review the information provided by manufacturers so that it can promote and protect the health of the public by ensuring the safety and effectiveness of medical devices deemed appropriate for human use (Food, Drug & Cosmetic Act, Section 903(b)(1, 2(C)), December 31, 2004; accessed December 17, 2008 http://www.fda.gov/opacom/laws/fdcact/fdctoc.htm). For high-risk devices, such as ventricular assist devices (VADs), mechanical heart valves, stents, cardiac resynchronization therapy (CRT) devices, pacemakers, and defibrillators, the determination is based on FDA's review of extensive preclinical bench and animal testing followed by use of the device in a clinical trial in humans. These clinical trials allow the manufacturer to evaluate a device in the intended use population. FDA reviews the data from the clinical trial to determine if the device performed as predicted and the clinical benefits outweigh the risks. This article reviews the regulatory framework for different marketing applications related to cardiovascular devices and describes the process of obtaining approval to study a cardiovascular device in a U.S. clinical trial.

Monitoring of heart rate variability in heart failure patients with cardiac resynchronisation therapy: Interest of continuous and didactic algorithm

Decreased autonomic function is known to be predictive of death, especially in chronic heart failure (CHF) patients. We sought to report mid-term heart rate and heart rate variability (HRV) changes after cardiac resynchronization therapy (CRT), using a continuous device-based measurement, which should facilitate daily management of CHF patients. Stored data were retrieved for 92 CHF patients who were enrolled in a prospective multicentre study and received a CRT pacemaker capable of continuous assessment of HRV. This parameter was recorded daily as a footprint plot, a graphic visualization of the distribution of HRV. Decreases in mean heart rate (from 75.4±11.7 to 71.4±8.4 bpm) and increases in HRV as attested by footprint area (from 33.5±13.5% to 40.7±14.5%) were statistically significant after 12 months follow-up (p<0.001). Patients with no change in footprint area were at greater risk for death, compared with other patients (HR 17.2, 95%CI 2.0–142.9, p<0.002). In conclusion, CRT provides sustained improvement of autonomic function, associated with an increased survival. The footprint plot is a simple graphic diagram, which may facilitate the practical and daily application of continuously measured HRV, thus assisting in the identification of high-risk CHF patients.

Mortality of Heart Failure Patients After Cardiac Resynchronization Therapy: Identification of Predictors

A direct comparison of survival benefits between cardiac resynchronization therapy-pacemaker (CRT-P) and defibrillator (CRT-D) was not yet performed, leaving clinicians to question whether CRT-P alone is enough to protect congestive heart failure (CHF) patients from sudden cardiac death and whether CRT-D should be implanted to all CHF patients indicated for biventricular pacing. This study attempts to make this type of comparison in a large CHF population and seeks to identify predictors of death in patients with different comorbidities. Study population consisted of 542 consecutive patients who were implanted with either CRT-P (N = 147) or CRT-D (N = 395) between 1999 and 2005. Patients' clinical and follow-up data were entered in a prospective registry and retrieved for analysis. The primary endpoint of this study was all-cause mortality during follow-up. Total all-cause mortality was significantly lower among patients with CRT-D (18.5% vs. 38.8% of CRT-P, chi(2)= 25.11, P < 0.001). Patients with one of three comorbidities--chronic renal failure (OR = 4.885, P = 0.005), diabetes mellitus (OR = 4.130, P = 0.003), and history of atrial fibrillation (OR = 1.473, P = 0.036)--appeared to have higher risk of death, while treatment with beta-blocker (OR = 0.330, P = 0.002) or CRT-D device (OR = 0.334, P = 0.003) seemed to be associated with lower mortality. Data from this nonrandomized study indicate that CRT-D has additional survival benefits over CRT-P. Given these findings, CRT-D should be recommended to most CHF patients with indications for biventricular pacing. After CRT implant, chronic renal failure, diabetes mellitus, and history of atrial fibrillation are strong independent predictors of death.

“Home monitoring” for early detection of implantable cardioverter-defibrillator failure

Telemedical ICD monitoring has the potential to enhance patient safety. The "home-monitoring" (HM) feature transmits selected device-related data to a service-center via mobile phone network. In case of a potential emergency situation, event reports are generated automatically. This prospective observational study was designed to test whether HM is effective and reliable in early detection of device failure. Consecutive patients receiving ICD, CRT-D or CRT pacemaker systems with HM feature were included. Regular follow-up visits were performed 1, 3, 6, 9 and 12 months after implantation in the first year, and every 6 months thereafter. All event reports transmitted by HM were analyzed and severe device-related events (serious lead or device dysfunction, hospitalization, death) were documented including timing, type and mode of detection. Sixty-nine patients were included and followed for 18 +/- 9 months. A total of 206 event reports were transmitted, prompted by VF/VT-episodes (n = 193), ineffective ICD shocks (n = 7), abnormal pacing impedance (n = 4) or battery depletion (n = 2). 8 SAEs were observed (RV lead fracture; n = 5, connector defect; n = 1, sensing defect, n = 1, RV lead dislodgement, n = 1). There was no device-related death. 6 out of 8 SAEs were discovered by HM (sensitivity, 75%). Without HM, these events would have been detected with a theoretical delay of 1.9 +/- 0.5 months in the first year (3 monthly FU) and 4.9 +/- 0.5 months in the following years (6 monthly FU). This pilot study demonstrates that HM enables early detection of ICD failure and appears to enhance patient safety.

Effect of Cardiac Resynchronization Therapy in Isolated Ventricular Noncompaction in Adults: Follow‐Up of Four Cases

An isolated ventricular noncompaction (IVNC) is an unclassified cardiomyopathy and, despite the increasing awareness of and interest in this disorder, the role of cardiac resynchronization therapy (CRT) remains obscure. The purpose of this study was to clarify the long-term effect of CRT on IVNC in adult patients. Four cases of IVNC were included in this study. Before the CRT device was implanted, all four patients (54 +/- 16-year-old, 4 males) presented with symptomatic congestive heart failure. Echocardiography revealed their systolic dysfunction and their left ventricular ejection fraction (LVEF) was 21 +/- 8%. There was also mechanical dyssynchrony observed between the LV septum and free wall area. The QRS duration was "narrow" (112 and 120 ms) in two patients. One patient had been resuscitated from ventricular fibrillation (VF) and two had nonsustained ventricular tachycardia (VT). A CRT defibrillator (CRT-D) was implanted in three patients with VT/VF and a CRT pacemaker (CRT-P) in a patient without VT/VF. The LV lead was positioned in a lateral branch of the coronary sinus where a thickened noncompacted wall existed. During the follow-up period (28 +/- 23 months), their congestive heart failure had improved in terms of the cardiothoracic ratio on the chest X-ray, B-type natriuretic peptide level, LV systolic dimension, and LVEF. No episodes of defibrillation shocks were observed. CRT may improve the prognosis and quality-of-life in patients with an IVNC with mechanical dyssynchrony.

Gender Disparity in the Use of Cardiac Resynchronization Therapy in the United States

Although several studies have shown the effectiveness of cardiac resynchronization therapy (CRT) for advanced congestive heart failure (CHF), gender differences in utilization of CRT are not known. We used the Healthcare Cost and Utilization Project (HCUP) to study national rates for admissions due to CHF along with procedures for initial CRT implantation, including both CRT-defibrillator (CRT-D) and CRT-pacemakers (CRT-P) during the years of 2002-2004. Chi-square tests were used for comparison between number of women and men. A P < 0.05 was considered significant. Women had consistently higher rates of admission for CHF during each year (574,037 (54%) vs 482,005 (46%), 2002; 601,181 (54%) vs 517,202 (46%), 2003; and 580,913 (53%) vs 521,280 (47%), 2004). The number of initial CRT device implantations (both CRT-D and CRT-P) was significantly lower during each year for women compared to men (659 (25%) vs 1,931 (75%), 2002; 6,928 (26%) vs 19,646 (74%), 2003; and 11,286 (27%) vs 42,196 (73%), 2004; P < 0.01 for all). Both CRT-P and CRT-D were used less frequently in women compared to men; however, this difference was consistently less prominent during each year with CRT-P compared to CRT-D (301 (41%) CRT-P vs 358 (19%) CRT-D, 2002; 659 (39%) CRT-P vs 2,530 (28%) CRT-D, 2003; and 2,891 (39%) CRT-P vs 8,395 (24%) CRT-D, 2004; P < 0.05). Our data clearly demonstrate a significant gender disparity in utilization of CRT devices. Further studies are needed to find possible reasons behind this disparity.

Cardiac Device Implantation in the United States from 1997 through 2004: A Population-based Analysis

OBJECTIVEUse of cardiac devices has been increasing rapidly along with concerns over their safety and effectiveness. This study used hospital administrative data to assess cardiac device implantations in the United States, selected perioperative outcomes, and associated patient and hospital characteristics.METHODSWe screened hospital discharge abstracts from the 1997–2004 Healthcare Cost and Utilization Project Nationwide Inpatient Samples. Patients who underwent implantation of pacemaker (PM), automatic cardioverter/defibrillator (AICD), or cardiac resynchronization therapy pacemaker (CRT-P) or defibrillator (CRT-D) were identified using ICD-9-CM procedure codes. Outcomes ascertainable from these data and associated hospital and patient characteristics were analyzed.MEASUREMENTS AND MAIN RESULTSApproximately 67,000 AICDs and 178,000 PMs were implanted in 2004 in the United States, increasing 60% and 19%, respectively, since 1997. After FDA approval in 2001, CRT-D and CRT-P reached 33,000 and 7,000 units per year in the United States in 2004. About 70% of the patients were aged 65 years or older, and more than 75% of the patients had 1 or more comorbid diseases. There were substantial decreases in length of stay, but marked increases in charges, for example, the length of stay of AICD implantations halved (from 9.9 days in 1997 to 5.2 days in 2004), whereas charges nearly doubled (from $66,000 in 1997 to $117,000 in 2004). Rates of in-hospital mortality and complications fluctuated slightly during the period. Overall, adverse outcomes were associated with advanced age, comorbid conditions, and emergency admissions, and there was no consistent volume–outcome relationship across different outcome measures and patient groups.CONCLUSIONSThe numbers of cardiac device implantations in the United States steadily increased from 1997 to 2004, with substantial reductions in length of stay and increases in charges. Rates of in-hospital mortality and complications changed slightly over the years and were associated primarily with patient frailty.

Abstract 2514: Automatic Biventricular Capture Verification Based On Morphological Analysis of the Intracadiac Electrogram Signal

Objective: We test a new biventricular capture verification algorithm, which can be used to adjust the pacing output in right ventricle (RV) and left ventricle (LV), to ensure the safety and efficacy of the cardiac resynchronization therapy (CRT). Methods: The algorithm calculates a novel index called ASCI, which measures the morphological similarity between the intracardiac electrogram (IEGM) signal and a template waveform representing captured paces. Ventricular capture (CAP) is verified if ASCI is greater than a predefined threshold, whereas non-capture (NC) is declared otherwise. CRT pacemakers were implanted in 6 dogs. During a mean follow-up of 23 days, 175 biventricular threshold tests were conducted by running a customized program, with various combinations of pace/sense polarities. Wideband RV and LV IEGM were recorded and downloaded for off-line analysis by the algorithm. Template signals for each pace/sense configuration in each chamber were created from the average of 4 captured beats. Each pace was annotated for CAP or NC by visual examination of the IEGM and based on stored data log of the pacing parameters. Results: A total of 9991 CAP paces (5104 RV, 4887 LV) and 4474 NC paces (2136 RV, 2338 LV) were eligible for morphology analysis. In both RV and LV, the calculated ASCIs were well separated for CAP and NC paces (Figure ): 0.83 ± 0.12 (RV CAP), 0.85 ± 0.11 (LV CAP), -0.06 ± 0.13 (RV NC), -0.07 ± 0.14 (LV NC). The classification accuracy of the algorithm remained &gt;= 99% for any ASCI threshold value choosing between 0.18 and 0.52. Conclusion: This study demonstrated the feasibility to perform automatic biventricular capture verification based on morphology analysis of the IEGM.

Therapeutic and diagnostic role of electrical devices in acute heart failure

Electrical devices, Cardiac Resynchronization Therapy (CRT) pacemakers, the Implantable Cardiac Defibrillator (ICD) and a combination of both, constitute an important line of treatment in the therapy of moderate to severe chronic heart failure. The effectiveness of these devices in the treatment of acute decompensated heart failure has yet to be systematically evaluated. However, the beneficial clinical effects of CRT translate into a marked reduction of heart failure-related hospitalization. Devices also offer unique diagnostic applications by continuous measurement of clinically useful physiological parameters over time. Of particular interest, monitoring of intrathoracic impedance and right ventricular pressures allows to detect changes in volume load in an early stage prior to the development of clinical symptoms. This information could be helpful to stop further progression to acute cardiac decompensation and to avoid hospitalization and acute clinical events. Using modern telecommunication technology, patients can also be remotely monitored in their daily living environment. In consequence, the incorporation of device technology into heart failure management programs calls for a close cooperation between heart failure specialists and electrophysiologists. This review addresses therapeutic and diagnostic aspects of device therapies in the context of acute heart failure.

Predicting mortality and rehospitalization in heart failure patients with Home Monitoring—

The increasing worldwide prevalence of heart failure is associated with numerous and protracted hospital admissions. The multidisciplinary team approach together with telemonitoring aims at reducing the number of rehospitalizations, length of hospital stay, and mortality rates. Novel cardiac resynchronization therapy (CRT) devices have a Home Monitoring capability, offering wireless, everyday transfer of the essential status and therapy data to the attending physician. The transmitted data include potential predictors of death or hospitalization, such as the onset of atrial and ventricular arrhythmias, duration of physical activity, mean heart rates over 24 h and at rest, percentage of CRT delivered, and lead impedances. We present here interim results of the prospective, longitudinal, multicenter Home CARE Phase 0 study, conducted in 123 patients (age: 67+/-9 years, 83% male) with clinical indication for CRT. Twenty-nine patients (24%) received a CRT pacemaker, 52 (42%) a prophylactic implantable cardioverter defibrillator (ICD), and 42 (34%) had other ICD indications. All devices have an integrated Home Monitoring feature. In a mean (interim) follow-up period of 3 months (9194 observational days), 11 unplanned rehospitalizations of cardiovascular etiology and 9 deaths occurred. In 70% of the rehospitalization events, the retrospective analysis of transmitted data via Home Monitoring revealed an increase in mean heart rate at rest and in mean heart rate over 24 h within 7 days preceding hospitalization. A decrease in the percentage of CRT was observed in 43% and a reduction in the patients' daily activity in 30% of rehospitalized patients. These interim findings suggest that Home Monitoring data may predict events leading to hospitalization and encourage further research.

Cardiac Resynchronization Therapy in Congestive Heart Failure Also Provides Beneficial Effects for Rhythm Control of Atrial Fibrillation

Two patients with dilated cardiomyopathy and persistent atrial fibrillation (AF) underwent successful electrical cardioversion and atrioventricular (AV) junction ablation, followed by implantation of a cardiac resynchronization therapy (CRT) pacemaker with a biventricular pacing system. The duration of persistent AF was one week in patient one and one year in patient two. The interventions resulted in marked improvement in refractory heart failure as well as rhythm control of AF. Patient one was free of AF at 11-month follow-up, and patient two had had markedly fewer episodes of paroxysmal AF during a follow-up period of 6 months. The anecdotal evidence in our two patients suggests that reduction of atrial size and atrial stretch after CRT and hence the atrial anatomical-electrical remodeling is the underlying mechanism for the improvement of rhythm control of AF.

Cardiac resynchronization therapy: a possible option for refractory end-stage heart failure

Background Cardiac resynchronization therapy (CRT) is an established option for patients with left ventricular (LV)asynchrony and heart failure (HF) in New York Heart Association (NYHA) Class III and stable patients in NYHA class IV. The application of CRT in an intensive care setting for patients with severe end stage refractory catecholamine dependent HF and LV asynchrony has not been highlighted so far. The case of a 64 year old female with dilated cardiomyopathy is reported. The patient was hospitalized for progressive dyspnea, hypotension, repetitive non sustained ventricular tachycardia, leg edema and renal failure under complete oral medication. Catecholamines had to be maintained at a minimum of 20 to 40 mg dobutamine/h. Treatment options included the implantation of abiventricular assist device or CRT. A stable catecholamine free status could not be achieved. Methods Dimensions of the heart, global ventricular function, heart valves and interventricular asynchrony were assessed by 2D and Doppler echocardiography.Intra LV asynchrony was assessed by tissue doppler. A CRT pacemaker and defibrillator (CRT-D) was implanted. Results The LV was dilated (71mm end diastolic) and the ejection fraction (EF) severely depressed (15%). Mitral regurgitation (MI) II° to III° was present. The interventricular mechanical delay (IVD) was 50 ms. The maximum intra LV difference (▵EMD max) of the electromechanical delay was 82 ms. The standard deviation of electromechanical delays (SDEMD) was 39ms. The myocardial performance index (MPI) was 1.75. After CRT-D implantation with mid lateral placement of the LV lead catecholamines could be discontinued within 20 hours, dyspnea and renal function improved rapidly. After 5 months LV diameter was 69mm, MI was I°. IVD was reduced to 10 ms, MPI to 0.63, EMDmax to 41 ms, SDEMD to 12 ms. The EF increased to 29% and the functional status was stable at NYHA class II to III. Conclusion Also in patients with catecholamine dependent refractory HF and marked LV asynchrony the implantation of a CRT device is a potentially helpful strategy which can avoid the application of an assist device and lead to stable improvement of hemodynamics and the patient's functional status. Further investigation is needed in this patient cohort.

Effect of av interval on the onset of mitral regurgitation in patients with cardiac resynchronization therapy

Since short AV intervals can cause interruption of left atrial transport due to left ventricular contraction, it has been proposed that alignment of the end of the A wave and the onset of mitral regurgitation (MR) could be used as markers to optimize left heart AV in patients (Pts) with CRT pacemakers. Since MR takes place only when the LV pressure is higher than the left atrial pressure, it was hypothesized that AV interval may play a role in the time of crossing of atrial and ventricular pressures. The aim of this study was to evaluate the relationship between AV interval (and thus the timing of left atrial contraction) and the time of onset of mitral regurgitation (MRt) in Pts with CRT devices. Three Pts with CRT devices (two Medtronic InSync III and one InSync III Marquis) implanted for medically intractable heart failure were studied by Doppler echocardiography. All patients had documented left ventricular capture and were clinically responders to CRT. Mitral Doppler flow tracings were obtained from the apical view, ensuring adequate simultaneous recording of the A wave and MR flow. AV intervals were programmed between 100 and 240 ms in the atrial pacing-biventricular pacing mode to insure rate stability. MRt was measured from the biventricular pacing pulse to the onset of MR flow. Results As the AV interval was shortened, the MRt lengthened from 18-25 ms (at AV of 240 ms) to 123-165 ms (at AV of 100 ms). In addition, at AV intervals shorter than 200 ms the mitral flow A wave became narrower and of smaller amplitude, suggesting flow reduction, although the A wave frequently remained visible and with an apparently normal shape. Regression analysis of MRt vs. AV interval revealed a best fit with a polynomial equation, with R2 >0.99 (p<0.001) for the three Pts. Since MR occurs only when the LV pressure exceeds left atrial pressure, it was assumed that with gradually shorter AVs, progressively higher left atrial pressure is needed to overcome rising LV pressure.Complete atrial transport block (disappearance of A wave) occurred only at very short AVs. Conclusion 1. AV interval modulates the onset of MR in CRT patients, thus alignment of A-wave and MR may not be a reliable marker of AV optimization. 2. A visible mitral Doppler A wave does not necessarily mean physiological left atrial transport mechanism, since it may be associated with increased left atrial pressure.

Initial experience with a new s-shaped bipolar lead for left ventricular pacing

Purpose This study evaluated the safety and efficacy of the new QuickSite™ 1056 T (St. Jude Medical, Sylmar, USA) left ventricular (LV) lead. QuickSite™ 1056 T is a polyurethane/silicon, 6 French, S-shaped, bipolar, Fast Pass™ coated, steroid eluting lead, which can be implanted using either a stylet-driven or an over-the-wire approach. Method 55 patients, candidates for Cardiac Resynchronization Therapy (CRT), were recruited in 18 European centers. Results Lead implantations were attempted in 55 patients. 51 implants were successful (overall success rate: 92.7%). When compared to the existing QuickSite™ 1056 K (unipolar) lead, the QuickSite™ 1056 T handling characteristics were classified as superior by more than one third of responding physicians (36%) and similar by 61%. 48 patients received an Epic/Epic+/Atlas+ HF CRT Defibrillator (CRT-D devices with independent ventricular channels and no LV sensing), 3 a Frontier CRT pacemaker (CRT-P device without independent channels). At implant and over the follow-up period, the electrical characteristics of the lead were good ([Table 1][1]). View this table: Table 1 Electrical characteristics (mean ± SD – CRT-D only) During follow-up, 1 lead had to be repositioned due to phrenic nerve stimulation. Another lead dislodged (2%) and had to be replaced. Conclusions The new QuickSite™ 1056 T LV lead offers good handling characteristics and good short term electrical characteristics and stability. [1]: #T1

Implantation of atriobiventricular pacemaker during cabg procedure ¿ description of 3 cases

We report on three cases of cardiac resynchronization therapy (CRT) system implantation during coronary artery bypass grafting (CABG) procedure. All 3 patients were men with coronary artery disease and postinfarction congestive heart failure in NYHA class III despite optimal medical treatment and without classical indications for permanent pacing. In echocardiography, intraventricular dyssynchrony was present in all patients. Methods During on-pump CABG epicardial bipolar leads (Medtronic CapSure Epi) were fixed on the right atrium, the right and left ventricle and connected to the CRT pacemaker (Medtronic InSync III) located in the left subclavicular portion. Postoperative period was uncomplicated. After 2 months pacing and sensing parameters remained excellent and significant clinical improvement was observed in all patients. Patients' characteristics and results (b=before, a=2 months after CABG + CRT) View this table: View this table: Conclusion CRT can be regarded as important supplement to surgical revascularization in still growing population of patients with severe heart failure and systolic dyssynchrony, for optimization of treatment results.

Cardiac resynchronization therapy

The rhythm of each heart beat is controlled by electrical pulses. These signals coordinate and synchronize the contraction of the atria and of the ventricles. They also provide the electrical sequence of activation that causes the ventricles to contract in a coordinated manner. In heart failure, this electrical sequence of activation is distorted A new surgical treatment can now be offered as an option to patients suffering from heart failure: cardiac resynchronization therapy (CRT). Implantable devices designed for CRT stimulate the two ventricles of the heart to beat at the same time by delivering tiny electrical pulses to both sides. This therapy is intended for patients with moderate to severe heart failure who also have ventricular dysynchrony, a condition in which the two ventricles are not beating synchronously. An example of a CRT device is a CRT pacemaker, which is a more advanced version of a standard pacemaker and is about the size of a pocket watch. Once implanted in the chest, the CRT pacemaker not only helps the heart keep a normal rhythm but improves contraction pattern in the left ventricle, improving the overall efficiency beneath the skin, usually below the collarbone. The performance of CRT devices was studied during the course of several clinical trials. The study showed that the CRT devices provide proven quality-of-life benefits to patients and funded hope for an increased life span.

La resynchronisation cardiaque : quel type d’appareil utiliser ?

Cardiac resynchronization therapy is indicated in advanced heart failure refractory to optimal drug treatment patients with left ventricular systolic dysfunction and QRS >120 milliseconds. The choice of the device has to consider several parameters: Do we have to implant a CRT pacemaker or a intracardiac cardioverter defibrillator (ICD)? The prevalence of sudden cardiac death is high in heart failure patients. In patients with an ischemic cardiomyopathy, primary prevention of sudden cardiac death trials suggests to implant a biventricular ICD. In patients with a non ischemic cardiomyopathy, the question is more controversial althought the resullts of the SCD-HeFT and COMPANION trials yielded interesting results for iCD implantation. However, the final decision has to consider the patient’s baseline characteristics such as age, presence of comorbidities and cost of the device. Today, devices with totally independent ports of the right and left ventricles have technical advantages and thus are more relevant. Cardiac resynchronization therapy is a heart failure treatment and the new devices provide new tools to assess heart failure parameters such as patient’s activity, respiratory parameters or heart rate variability. Left ventricular pacing alone is currently under evaluation such as atrial fibrillation prevention algorithms, atrial fibrillation being frequent in herta failure patients with hemodynamic deleterious consequences.