Implantable Defibrillator Devices Research Articles

Impact of SLGT2 inhibitors treatment initiation on the reduction of atrial and ventricular arrhythmias in patients with implanted cardiac defibrillator

Abstract Introduction Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) have been associated with improved prognosis in patients with heart failure; however, their impact on atrial arrhythmic (AA) and ventricular arrhythmic (VA) events is not fully understood. Methods Retrospective multicentric study of heart failure patients with implantable cardiac defibrillator device (ICD) from 2015 to 2020 with or without cardiac resynchronization therapy (CRT) receiving SGLT2 inhibitors. Device-registered arrhythmic events were analyzed and compared in two time periods for each patient: one year before and one year after starting SGLT2i. Relevant VA were defined as the occurrence of any sustained VT (SVT) (>30 seconds), ventricular fibrillation (VF), or appropriate therapy (antitachycardia pacing or shock). All VA included all the relevant VA and the occurrence of non-sustained ventricular tachycardia (NSVT). AA included atrial fibrillation (AF) burden, and episodes of more than 24 hour of AF. Results A total of 195 patients (66.8 [61.3-73.1] years, 18.5% women) were included. A reduction was observed in the percentage of patients with any VA (pre: 52.3% vs post: 30.3%; P < 0.001) and clinically relevant VA (excluding NSVT) (pre: 21.5% vs post 8.7%; P < 0.001) in the post-SGLT2i period. There was also a reduction in the number of episodes per patient/year of NSVT (pre: 2 (1-5) vs post: 1 (0-2); P < .001), and SVT (pre: 1 (1-3) vs post: 0 (0-2); p = 0.046). This protective effect was also observed after controlling confusion factors (Any VA: OR 0.35 (0,24-0,50); p<0.001 and relevant VA: OR 0.30 (0,17-0,52); p<0.001). However, no differences were observed in the prevalence of AA (24.7% vs 18.8%; P = 0.117) or the burden of atrial fibrillation (pre: 0% (0-0.1) vs post 0% (0-0); p = 0.097). Conclusions Following the initiation of SGLT2i treatment, a reduction in the percentage of patients with relevant VA was observed. However, this effect was not observed for AA.Figure 1Figure 2

Impact of sodium-glucose cotransporter-2 (SLGT2) inhibitors treatment initiation on the reduction of atrial and ventricular arrhythmias in patients with implanted cardiac devices

Abstract Introduction Sodium-glucose cotransporter-2 (SLGT2) inhibitors have demonstrated benefits on survival and hospital admissions in patients with heart failure and reduced ejection fraction. However, their impact on the burden of ventricular (VA) and atrial arrhythmias (AA) is unknown. Methods Retrospective multicentric study of heart failure patients with implantable cardiac defibrillator device (ICD) from 2015 to 2020 with or without cardiac resynchronization therapy (CRT) receiving SGLT2 inhibitors. Device-registered arrhythmic events were analyzed and compared during one year following SLGT2 inhibitor initiation and during one year before initiation. Relevant VA were defined as the occurrence of any sustained VT (SVT) (>30 seconds), ventricular fibrillation (VF), or appropriate therapy (antytachycardia pacing or shock). All VA included all the relevant VA and the occurrence of non-sustained ventricular tachycardia (NSVT). AA included atrial fibrillation (AF) burden, and episodes of more than 24 hour of AF. Results 147 patients (67 ± 10 years, 82.3% males, LVEF 30.3 ± 11%, CRT 39.3%), were included in the study. 77.6% had complete remote tele-monitoring during the entire follow up and there was no difference in the antiarrhythmic therapy between the two periods. Following SGLT2 inhibitor initiation, there was a significant reduction in the percentage of patients with relevant VA (19.7% pre vs 10.9% post; p=0.019) and all VA (47.6% pre vs 30.6% post; p<0.001) (Figure 1 and 2). There was a reduction in the prevalence of NSVT (40.1% pre vs. 27.2% post; p<0.001), of SVT (17.7% vs 8.8%; p<0.001), of VF (4.1% vs 2%; p=NS) and appropriate therapies (14.3% vs 9.5%; p=NS). Among patients with any VA, there was a significant reduction in the incidence of NSVT (p<0.001), but not in the incidence of SVT or appropriate therapies (p=NS). There was no impact on atrial fibrillation burden or in the number of AF episodes lasting more than 24 hours (p=NS). Conclusions In our study, initiation of a SGLT2 inhibitor in patients with heart failure, was associated with a reduction in the prevalence of relevant VA and any VA, with a significant reduction in the number of NSVT per patient. There was no impact on AF burden or the number of AF episodes lasting more than 24 hours. Prospective studies should be performed to sustain these conclusions.Relevant ventricular arrhythmiasAny ventricular arrhythmia

PRecision Event Monitoring for PatienTs with Heart Failure using HeartLogic (PREEMPT-HF) study design and enrolment.

The HeartLogic multisensor index has been found to be a sensitive predictor of worsening heart failure (HF). However, there is limited data on this index's association and its constituent sensors with HF readmissions. The PREEMPT-HF study is a global, multicentre, prospective, observational, single-arm, post-market study. HF patients with an implantable defibrillator device or cardiac resynchronization therapy with defibrillator with HeartLogic capabilities were eligible if sensor data collection was turned on and the HeartLogic feature was not enabled. Thus, the HeartLogic Index/alert and heart sounds sensor trends were unavailable via the LATITUDE remote monitoring system to clinicians (blinded). Evaluation of subject medical records at 6months and a final in-clinic visit at 12months was required for collection of all-cause hospitalizations and HF outpatient visits. The purpose of this study is exploratory, no formal hypothesis tests are planned, and no adjustment for multiple testing will be performed. A total of 2183 patients were enrolled at 103 sites between June 2018 and June 2020. A significant proportion of the patients were implanted with implantable defibrillator devices (39%) versus cardiac resynchronization therapy with defibrillator (61%); were female (27%); over 65 (61%); New York Heart Association class I (13%), II (53%), and III (33%); ejection fraction<25% (21%); ischaemic (50%); and with a history of renal dysfunction (23%). The PREEMPT study will provide clinical data and blinded sensor trends for the characterization of sensor changes with HF readmission, tachyarrhythmias, and event subgroups. These data may help to refine the clinical use of HeartLogic and to improve patient outcomes.

PO-05-078 SHOCK REDUCTION THROUGH EARLY DELIVERY OF ANTITACHYCARDIA PACING FOR FAST VENTRICULAR TACHYCARDIAS

Antitachycardia pacing (ATP) is a programmable therapy in implantable cardiac defibrillator (ICD) devices that has been demonstrated to effectively reduce the need for shocks. Limited data, however, exists on the potential benefits of early ATP delivery in the ventricular fibrillation (VF) zone. While ATP is programmed to be delivered as a first line of therapy for ventricular tachycardia (VT) events, it does so only once the episode meets detection criteria by the ICD. Newer generations of BIOTRONIK ICDs have the ability for earlier delivery of ATP, called Early ATP OneShot, to be programmed in the VF therapy zone. Early ATP is delivered when 12 out of 16 events, plus stability criteria, are met to target fast VTs detected in the programmed VF therapy zone. This option is available for patients with longer detection times (VF detection counters of 16 out of 20 or higher) and allows the device to deliver ATP before episode detection counter criteria is met, thus providing therapy earlier than traditional ATP. To compare the success rates of Early ATP OneShot (eATP) for episodes in the VF zone against traditional ATP OneShot (tATP) programming. Using BIOTRONIK’s real-world research database, CERTITUDE, 696 patients with eATP capable ICD devices with VF episodes transmitted via remote monitoring were divided into groups based on tATP (n=584) or eATP (n=112) programming for the VF therapy zone. Each device detected episode was evaluated to determine the therapy (ATP and/or shocks) delivered, whether therapy was successful, or if the episode self-terminated. Patients with detection zone counters lower than 16 out of 20 were excluded. eATP was successful in 69.4% of cases in terminating episodes in the VF zone whereas tATP was successful in 49.1% of cases (p<0.0001). Extrapolation of the eATP success rate to the tATP cohort results in 30.0% less shocks (203 avoided shocks out of 676 total shocks). Cohorts did not differ statistically in mean R-R interval at episode detection, nor in device programming for detection limit zone or counters. Episode duration was shorter in the eATP cohort (p<0.0001). As compared to traditional programming, use of Early ATP OneShot provides increased success rates to terminate fast VTs detected in the VF zone, potentially reducing unnecessary shocks.Tabled 1Table: Comparison of ATP Therapy Groups for Device Detected VF Episodes (PO-05-078)OutcomeEarly ATP OneShotTraditional ATP OneShotp value (difference)Patients with VF Event112584-ATP Therapy Success Rate (Successes/Attempts)69.4% (161/232)49.1% (491/1001)<0.0001Median VF Episode Duration (sec)1217<0.0001Mean R-R interval at VF Episode Detection (ms)2572530.17Mean Programmed Rate of VF Detection Limit (ms)2882910.20Median Programmed Detection Counters for Programmed VF Zone (X/Y criteria)18/2418/240.94 Open table in a new tab

Implantable Cardiac Device Infections Prevalence: Diagnostic and Therapeutic Implications

Background: It has been demonstrated that the use of cardiac implanted electronic devices (CIED) improve mortality and survivability in a variety of patient populations. Nevertheless, CIED related infection is a serious complication characterized by a high rate of mortality and morbidity.&#x0D; Objectives: To evaluate the prevalence of CIED related infections, risk factors, clinical and demographic characteristics, causative organisms, and the management and outcome of patients presented in the Critical Care Department, Cairo University.&#x0D; Methods: A retrospective analysis was conducted in 1871 individuals who had been implanted with a cardiac device with a total number of devices of 1968 and 2270 procedures performed from January 2007 to December 2017.&#x0D; Results: 59 infectious episodes were identified with an estimated incidence of 2.99% of inserted devices and 2.6% of total procedures. The infection rate was considerably higher in patients with multiple procedures than those who had a single procedure (9.27% vs. 1.18%; P&lt;0.001). The individuals with a dual-chamber implantable cardiac defibrillator (ICD) and cardiac resynchronization therapy devices (CRTD) had the highest infection rate of 6.25% &amp; 6.85%, respectively. The rate of pocket infection (PI) and CIED related endocarditis (CDE) was 1.54% &amp; 1.06% of total devices respectively. Numerous risk factors have been found; the most significant of those are diabetes mellitus, recurrent procedures, the device's complexity, and the existence of more than one lead. Gram-positive cocci were the most isolated organisms in all positive cultures (69.23%). Echocardiography revealed lead vegetations and valvular vegetations in 22 patients and 2 patients respectively. In 53 cases (89.83%), the devices were removed; in 41 cases, the entire system was removed; and in 12 cases, only the generator was removed. The mortality rate was found to be 10.17%, having a considerably higher prevalence in CDE individuals than in pocket infection individuals (20.83% vs. 2.86%; P=0.025).&#x0D; Conclusion: In our center, while the rate of CIED implantation continues to increase, the incidence rate of CIED-related infection continues to decline. Until now, the infection burden associated with secondary intervention is still significantly high. The management strategy of selection is to eliminate the entire system for patients presented with infection especially those with CDE. However, the mortality rate is still high.

An up-to-date review of cardiac pacemakers and implantable cardioverter defibrillators.

Cardiac pacemakers are one of the most frequently encountered cardiac devices seen on chest imaging. They may include single or dual chamber pacemakers, automated implantable cardioverter defibrillators (AICD), biventricular pacemakers used for cardiac resynchronisation therapy (CRT), wireless CRT, leadless pacemakers, and subcutaneous implantable cardioverter defibrillators (SICD). This review aims to provide an up-to-date review on current implantable pacemaker and defibrillator devices.

Ablation therapy of postural orthostatic tachycardia syndrome, inappropriate sinus tachycardia and primary electrical diseases: new insights in invasive treatment options in severely symptomatic patients.

Achieving the goal management of some arrhythmic syndromes can be challenging; medical treatment for inappropriate sinus tachycardia (IST) and postural orthostatic tachycardia syndrome (POTS) may be ineffective, necessitating multidisciplinary team treatment. Implantable defibrillator devices (ICDs), along with anti-arrhythmic drugs (AADs), remain the first-line treatment for primary electrical diseases that pose arisk of sudden cardiac death (SCD). Ablation of the arrhythmogenic substrate is not always suggested in patients with these pathologies, but it may be avaluable support for reducing arrhythmic burden, improving quality of life, and treating pathologies that are resistant to pharmacological treatment; however, this option is not often considered due to the potential risks associated with an invasive approach. Minimally invasive hybrid ablation in these syndromes, such as ahybrid thoracoscopic approach and the use of non-invasive mapping systems, reduces post-surgery complications and ensures the best possible outcome for the patient.

Prediction of paroxysmal atrial fibrillation using new heart rate variability features

Paroxysmal atrial fibrillation (PAF) is a cardiac arrhythmia that can eventually lead to heart failure or stroke if left untreated. Early detection of PAF is therefore crucial to prevent any further complications and avoid fatalities. An implantable defibrillator device could be used to both detect and treat the condition though such devices have limited computational capability. With this constraint in mind, this paper presents a novel set of features to accurately predict the presence of PAF. The method is evaluated using ECG signals from the widely used atrial fibrillation prediction database (AFPDB) from PhysioNet. We analysed 106 signals from 53 pairs of ECG recordings. Each pair of signals contains one 5-min ECG segment that ends just before the onset of a PAF event and another 5-min ECG segment at least 45 min distant from the PAF event, to represent a non-PAF event. Seven novel features are extracted through the Poincaré representation of R-R interval signals, and are prioritised through feature ranking schemes. The features are used with four standard classification techniques for PAF prediction and compared to the existing state of the art from the literature. Using only the seven proposed features, classification performance outperforms those of the classical state-of-the-art feature set, registering sensitivity and specificity measurements of over 96%. The results further improve when the features are combined with several of the classical features, with an accuracy increasing to 98% using a linear kernel SVM. The results show that the proposed features provide a useful representation of the PAF condition and achieve good prediction with off-the-shelf classification techniques that would be suitable for ICU deployment.

Electrical Storm Due to Active Myocardial Ischemia in the Right Coronary Artery Territory – Case Report

Abstract Electrical storm is defined by at least three episodes of sustained ventricular tachyarrhythmias or appropriate shocks given by implantable cardiac defibrillator devices (ICD), occurring within a period of 24 hours. In the present manuscript, we present the case of a 69-year-old female patient with previous aortocoronary bypass, who was admitted from the Emergency Department after presenting several episodes of syncope in prehospital settings and presented 4 episodes of sustained ventricular tachycardia which required electrical cardioversion. The arrhythmia disappeared after percutaneous revascularization of a chronic occlusion in the right coronary artery. In this case, the implantation of an ICD was avoided, as a reversible cause of ES has been identified and treated.

Ruptured Intracranial Mycotic Aneurysm in Infective Endocarditis With Left Ventricular Assist Device and Implantable Cardiac Defibrillator Device: A Clinical Course

We report the first case of a ruptured intracranial aneurysm-related Staphylococcus epidermidis bacteremia in a patient supported by a continuous flow left ventricular assist device (LVAD). Mycotic aneurysms (MAs) are aneurysmal degeneration of the arterial wall as a result of infection. Current recommendations for management of intracranial mycotic aneurysms are based on a few retrospective case studies. There are only a few cases of intracranial MA reported in patients with LVAD infections caused by Pseudomonas aeruginosa and Klebsiella rhinos. Here, we describe the first case of a ruptured intracranial aneurysm caused by a less virulent organism (Staphylococcus epidermidis) and conclude that screening for asymptomatic MA should be strongly considered in patients with persistent LVAD- and implantable cardiac defibrillator pacemaker–associated infections.

Prognostic value of global longitudinal strain in heart failure patients treated with cardiac resynchronization therapy

Myocardial fibrosis (macroscopic scar or diffuse reactive fibrosis) is one of the determinants of impaired left ventricular (LV) global longitudinal strain (GLS) in heart failure (HF) patients. The purpose of this study was to evaluate the prognostic value of LV GLS in HF patients treated with cardiac resynchronization therapy (CRT). The study included 829 HF patients (mean age 64.6 ± 10.4 years; 72% men) treated with CRT. Before CRT implantation, LV GLS was assessed using 2-dimensional speckle tracking echocardiography. The primary endpoint was the combination of all-cause mortality, heart transplantation, and LV assist device implantation. The secondary endpoint was the occurrence of ventricular arrhythmias or appropriate implantable defibrillator device therapies. During follow-up, 332 patients reached the primary endpoint, and 233 presented with the secondary endpoint. Patients were divided according to LV GLS quartiles. Patients with the most impaired LV GLS quartile had a 2-fold higher risk of reaching the combined endpoint compared with patients in the best LV GLS quartile (hazard ratio [HR] 2.088; 95% confidence interval [CI] 1.555-2.804; P <.001). LV GLS was significantly associated with the combined endpoint (HR 1.075; 95% CI 1.020-1.133; P = .007) after adjusting for clinical, electrocardiographic, and echocardiographic characteristics. Although patients in the most impaired LV GLS quartile showed higher event rates for the secondary endpoint compared with the other groups, LV GLS was not independently associated with the secondary endpoint (HR 1.047; 95% CI 0.989-1.107; P = .115). In this large cohort of CRT patients, baseline LV GLS was independently associated with the combined endpoint.

Effects of angiotensin-neprilysin inhibition compared to angiotensin inhibition on ventricular arrhythmias in reduced ejection fraction patients under continuous remote monitoring of implantable defibrillator devices

Angiotensin-neprilysin inhibition compared to angiotensin inhibition decreased sudden cardiac death in patients with reduced ejection fraction heart failure (rEFHF). The precise mechanism remains unclear. The purpose of this study was to explore the effect of angiotensin-neprilysin inhibition on ventricular arrhythmias compared to angiotensin inhibition in rEFHF patients with an implantable cardioverter-defibrillator (ICD) and remote monitoring. We prospectively included 120 patients with ICD and (1) New York Heart Association functional class ≥II; (2) left ventricular ejection fraction ≤40%; and (3) remote monitoring. For 9 months, patients received 100% angiotensin inhibition with angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB), beta-blockers, and mineraloid antagonist. Subsequently, ACEi or ARB was changed to sacubitril-valsartan in all patients, who were followed for 9 months. Appropriate shocks, nonsustained ventricular tachycardia (NSVT), premature ventricular contraction (PVC) burden, and biventricular pacing percentage were analyzed. Patients were an average age of 69 ± 8 years and had mean left ventricular ejection fraction of 30.4% ± 4% (82% ischemic). Use of beta-blockers (98%), mineraloid antagonist (97%) and antiarrhythmic drugs was similar before and after sacubitril-valsartan. Sacubitril-valsartan significantly decreased NSVT episodes (5.4 ± 0.5 vs 15 ± 1.7 in angiotensin inhibition; P <.002), sustained ventricular tachycardia, and appropriate ICD shocks (0.8% vs 6.7% in angiotensin inhibition; P <.02). PVCs per hour decreased after sacubitril-valsartan (33 ± 12 vs 78 ± 15 in angiotensin inhibition; P <.0003) and was associated with increased biventricular pacing percentage (from 95% ± 6% to 98.8% ± 1.3%; P <.02). Angiotensin-neprilysin inhibition decreased ventricular arrhythmias and appropriate ICD shocks in rEFHF patients under home monitoring compared to angiotensin inhibition.

Cost-consequence analysis of daily continuous remote monitoring of implantable cardiac defibrillator and resynchronization devices in the UK

AimsThe need for ongoing and lifelong follow-up (FU) of patients with cardiac implantable electric devices (CIED) requires significant resources. Remote CIED management has been established as a safe alternative to conventional periodical in-office FU (CFU). An economic model compares the long-term cost and consequences of using daily Home Monitoring® (HM) instead of CFU.Methods and resultsA cost–consequence evaluation comparing HM vs. CFU was performed using a Markov cohort model and data relating to events and costs identified via a systematic review of the literature. The model is conservative, without assuming a reduction of cardiovascular events by HM such as decompensated heart failure or mortality, or considering cost savings such as for transportation. Also cost savings due to an improved timing of elective device replacement, and fewer FU visits needed in patients near device replacement are not considered. Over 10 years, HM is predicted to be cost neutral at about GBP 11 500 per patient in either treatment arm, with all costs for the initial investment into HM and fees for ongoing remote monitoring included. Fewer inappropriate shocks (−51%) reduce the need for replacing devices for battery exhaustion (−7%); the number of FU visits is predicted to be halved by HM.ConclusionFrom a UK National Health Service perspective, HM is cost neutral over 10 years. This is mainly accomplished by reducing the number of battery charges and inappropriate shocks, resulting in fewer device replacements, and by reducing the number of in-clinic FU visits.

Viewing Cardiovascular Research Through the Eyes of Past, Present, and Future Generations

WILLIAM HARVEY, THE 17TH-CENTURY ENGLISH physician who first correctly described how the heart pumped blood around the body, was quoted as saying, “All we know is still infinitely less than all that remains unknown.” To his credit and humility, he understood that his work only set the stage for many discoveries yet to come. All physicians could learn important lessons from Harvey. Looking back to past research can provide interesting insights into how the field of cardiovascular medicine got to where it is and also important hints on where it may be going. Yet historical reviews can also be humbling, demonstrating how prior generations had inaccurately interpreted their findings and in other cases, how slow clinicians have been in adopting past advances. It is therefore appropriate that JAMA’s 2012 cardiovascular disease theme issue includes “The Resuscitation of the Heart,” an editorial originally published 100 years ago. The article describes how experiments using cardiac massage and electrical stimulation in dogs had shown promise in bringing animals back from the dead. The results seemed miraculous to the authors owing to their rudimentary understanding of cardiac physiology, yet they still foresaw the future of cardiopulmonary resuscitation (CPR) and cardiac defibrillator therapy in humans. It would be another 35 years, however, before the first successful defibrillation of an exposed human heart was performed; another 45 years until the first closed chest cardiac defibrillators came to routine use; and nearly 70 years until the first implantable defibrillator device would reach the market. Perhaps most concerning, even today, only a small proportion of the US population has received CPR training, cardiac defibrillator response time even in hospitals is far from ideal, and only up to two-thirds of patients eligible for an implantable defibrillator actually receive the device. Certainly in these cases, the translation of experimental concepts to routine cardiology practice has been less than ideal in these cases. In this theme issue of JAMA, readers can view some of the latest contemporary cardiovascular discoveries. Three epidemiological studies examine the prevalence of cardiac risk factors and their association with clinical events in various populations. It may seem remarkable that more than 50 years after the basic cardiac risk factors were first described there is more to say, yet each of these latest contributions provides important, novel insights. In one report, Wilkins and colleagues use nearly 1 million person-years of follow-up data from large cohort studies to estimate lifetime risk of cardiovascular disease (CVD). Their study found that the lifetime odds for CVD are proportional to the number of cardiac risk factors. Importantly, those with an “optimal” risk factor profile at midlife have a several-fold lower lifetime likelihood for cardiac events compared with those with multiple risk factors. Many of the major cardiac cohort studies to date were conducted in predominantly white populations, and they thus fail to reflect the racial and ethnic diversity of the United States. Studying a broad, racially diverse cohort, Safford and colleagues address this epidemiological gap and find that both black men and black women have a nearly 2-fold higher risk for fatal cardiac events relative to their white peers. However, the study also points out that these differences reflect the high burden of cardiac risk factors seen in black patients. An additional article by Daviglus and colleagues identifies similar issues among those of Hispanic origin. This report is the first major publication from the Hispanic Community Health Study/Study of Latinos, a very large National Institutes of Health–sponsored initiative to characterize CVD in diverse US Latino populations. The researchers note the high burden of cardiac risk factors in Latino populations, particularly among those of Puerto Rican origin, lower socioeconomic background, and more acculturation into the US lifestyle. Taken together, these 3 articles highlight the pressing need (and incredible opportunity) for primary and secondary prevention interventions to reduce CVD death and disability among all racial/ethnic groups in the United States. Beyond epidemiology, cardiovascular medicine also advances through direct human experimentation. Randomized clinical trials (RCTs) provide ideal tools to confirm (or

Feasibility of using multivector impedance to monitor pulmonary congestion in heart failure patients

Pulmonary edema (PE) is associated with fluid accumulation in the lungs. Device-based impedance measurements have been used to detect fluid overload prior to hospitalization. However, studies have reported a high false positive rate (FPR). The objective of this study was to develop and test a new multivector impedance-based algorithm that reliably tracks PE clinical events. We enrolled patients with implanted CRT-Ds in 23 US centers within 2 weeks of device implant. Six-vector impedance data was collected automatically by the CRT-Ds every 30 min during emergency department visits/hospitalizations and every 2 h at all other times. Detection algorithms for cardiac resynchronization therapy defibrillator (CRT-D) and implantable cardiac defibrillator (ICD) devices were developed using those impedance vectors that would be available in corresponding devices and retrospectively evaluated. There were 75 patients (69 % male), mean age 66 ± 12 years, with a LVEF of 23 ± 6 % and QRS of 149 ± 25 ms. Twenty-one major clinical events occurred over 8.2 ± 2.6 months of follow-up time. CRT-D vector combinations resulted in a sensitivity of 71.4 % (95 % confidence interval 47.8-88.7) and a FPR of 0.56 (0.30-0.94) false positives per patient-year (FPs/pt-yr); ICD vector combinations resulted in a sensitivity of 61.9 % (38.4-81.9) and a FPR of 0.63 (0.36-0.90) FPs/pt-yr. In comparison, the single-vector RVCoil-Can implementation of this algorithm resulted in a sensitivity of 57.1 % (34.0-78.2) and a FPR of 0.74 (0.44-1.12) FPs/pt-yr. This multivector impedance algorithm was effective in tracking PE clinical events in this patient population. Additional studies are needed to prospectively evaluate the performance of this algorithm in a larger population.

Clinical trials of antiarrhythmic therapies and optimizing health care resource deployment: the need for a paradigm shift

Randomized clinical trials (RCTs) of antiarrhythmic therapies have proliferated since they replaced observational clinical reports over two decades ago. Challenged initially at almost every step, from ethics to endpoints, RCTs have formed the bedrock of evidence-based medicine and practice guidelines in cardiac arrhythmias. Yet the implementation of evidence-based diagnostic or therapeutic guidelines suitable for clinical practice has not been without difficulty. Some have evoked an uneasy acceptance in many quarters and others even more difficult execution in medical practice. Examples abound. The rate versus rhythm debate in atrial fibrillation (AF) management is a prominent one. Clinical trial outcomes were more readily accepted by generalists than specialists, with the latter perplexed by the unexpected outcome that ran counter to physiologic principles and lacked a robust and complete explanation [1, 2]. Prophylaxis of sudden death events in clinical practice using implantable defibrillator devices in high-risk patients resulted in unused device therapy in a very large proportion of all recipients [3]. These non-uniform outcomes are also seen in cardiac resynchronization therapy and ablation of an increasingly broad spectrum of the AF population [4, 5]. Recently, these foundational clinical trials have been revisited in part or in great measure [6, 7]. These reports have been both enlightening and concerning. They enlighten us by revealing common underlying threads of behavior in arrhythmia disorders. They evoke concern in two areas. Firstly, by revealing serious adverse effects of long established and widely employed therapeutic interventions; and secondly, that our current paradigms of clinical trial design and patient enrollment result in highly variable benefits with a serious proportion of patients receiving little or no longterm benefit from the intervention. Statisticians remind us regularly of the perils and pitfalls of both retrospective visits to clinical trial data and subgroup analyses. To paraphrase a distinguished editor of this Journal, there should be due caution around “relying on subgroup analyses or declaring a difference when there is none and vice versa.” This concern arises mostly due to lack of statistical power in the original trial design for the subgroup analysis, which may actually mask potential benefit or harm. At best, we accept the premise that these subgroup analyses can be construed as hypothesis generating. We do appear to be better at selecting subgroups that achieve significant harm in clinical trials with safety monitoring. However, the implications of looking away from highly visible patterns of behavior in clinical outcomes have enormous implications for both patients subjected to unnecessary care and wasted resources in a resource-limited global health care environment. For example, with direct and indirect cardiac resynchronization defibrillator expenditures exceeding three billion US dollars in this year past, nonresponders to this therapy contributed over one billion dollars in cost. Some of these individuals could be simply identified by baseline characteristics at implant, according to trial subgroup analyses. In this authors’ view, it is time for a paradigm shift in health care resource deployment that does take into account important subgroup data. What are common threads of behavior in arrhythmia outcomes? They appear to lie in three different areas. Firstly, a clear understanding of important baseline variables in recruited populations that will impact outcomes. Managing S. Saksena (*) UMDNJ-Robert Wood Johnson School of Medicine, 161 Washington Valley Road, Suite 201, Warren, NJ 07059, USA e-mail: DRSSEPNJ@aol.com

Interaction Between Enfuvirtide, an Injectable Fusion Inhibitor, and Niacin in an HIV-Infected Patient

To report a potential drug-drug interaction between enfuvirtide, an injectable HIV fusion inhibitor, and niacin in an HIV-infected man with dilated cardiomyopathy. A 47-year-old HIV-infected man with dilated cardiomyopathy and prolonged QT syndrome with an automatic implantable cardiovascular defibrillator device was prescribed subcutaneous enfuvirtide 90 mg twice daily as part of his antiretroviral regimen and oral extended-release niacin 500 mg/day for a high-density lipoprotein level of 8 mg/dL. After 1 week of concomitant therapy, the patient began experiencing extreme redness, edema, and swelling at the injection site that corresponded with the flushing sensation due to niacin. This interfered with his daily activities, leading to self-discontinuation of both agents. As the patient had tolerated enfuvirtide therapy prior to the addition of niacin, we reinitiated enfuvirtide with close follow-up, and the patient has been maintained on this agent since then without consequence. Based on the Horn Drug Interaction Probability Scale, a probable interaction occurred between enfurvirtide and niacin. We hypothesize that a drug-drug interaction occurs between enfuvirtide and niacin related to prostaglandin synthesis and mobilization of inflammatory cells, specifically Langerhans cells. A theoretical mechanism for this interaction is that the Langerhans cells in the epidermis function improperly due to the presence of HIV and the attachment of enfuvirtide. When these cells are exposed to nicotinic acid, an exaggerated immune response is produced that may lead to pain, redness, and swelling at the injection site. Prostaglandins, cytokines, and other inflammatory molecules may all have a role in this interaction. Caution should be used when coadministering enfuvirtide and niacin to HIV-infected patients.

What We Have Learned From the Family of Multicenter Automatic Defibrillator Implantation Trials

Electrical device therapy began 50 years ago with the external defibrillator, and was followed subsequently with the introduction of implantable cardiac pacemakers, defibrillators, and resynchronization devices to prevent bradycardia, sudden arrhythmic death, and heart failure. During the past 20 years the Multicenter Automatic Defibrillator Implantation Trial (MADIT) research group has carried out a series of trials, including the MADIT-I, MADIT-II, and MADIT-III (MADIT-CRT), that have focused on improving the outcomes for patients with ischemic and nonischemic cardiac disease. The most recent MADIT-CRT trial showed that a cardiac resynchronization therapy device with defibrillator (CRT-D) was effective in reducing the risk of heart failure or death, whichever came first, in cardiac patients who were asymptomatic or minimally symptomatic (New York Heart Association class I or II) with reduced ejection fraction < or =0.30 and wide QRS complex > or =130 ms when compared with an implantable cardiac defibrillator (ICD) device. The family of MADIT ICD and CRT-D trials have provided a firm foundation for improving the clinical management of at-risk cardiac patients as the second decade of the 21(st) century begins.

Current status of implantable defibrillator devices in patients with left ventricular dysfunction — The first report from the online registry database

Background: The current status of the efficacy of implantable cardioverter‐defibrillator (ICD. and cardiac‐resynchronization therapy with implantable defibrillator (CRT‐D. in patients with left ventricular dysfunction needs to be clarified.Methods and Results: From the Japanese Cardiac Device Treatment Registry database, a total of 1,584 patients who had an LVEF ≦ 40% and had an ICD or CRT‐D were selected as subjects in this study. The difference in the clinical characteristics between the primary and secondary prevention groups and the transition of the indications for device implantation over time were examined. Primary prevention gradually increased up to about 50% in all patients. The implantations of ICD/CRT‐D for primary prevention in ischemic hear disease was significantly lower than that in dilated cardiomyopathy (33% vs 51%; p &lt; 0.0001). The number of implantations for CRT‐D for primary prevention increased dramatically over a one‐year period.Conclusions: In Japan, the implantable defibrillator devices for primary prevention was significantly lower in ischemic heart disease compared with dilated cardiomyopathy. Further, an extension of the indications for ICD/CRT‐D implantations has recently been occurring, especially with CRT‐D devices for primary prevention.

Catheter Ablation of Ventricular Tachycardia

A B S T R A C T Catheter ablation is highly successful and may be considered as the first line treatment in all symptomatic idiopathic forms of ventricular tachycardia (VT). Also ablation plays an important role in recurrent VTs associated with structural heart disease and relatively preserved left ventricular ejection fraction (>35%) and/or bundle branch reentry VT. It also constitutes the preferable treatment modality in incessant VTs of any origin and in patients with implantable defibrillator (ICD) devices who present with recurrent VTs and/or an electrical storm leading to multiple ICD shocks Catheter ablation appears to improve arrhythmia control in about two thirds of patients with structural heart disease and mappable VTs. Novel substrate and/or noncontact mapping techniques suggest that even hemodynamically unstable VTs and/or VTs of multiple morphologies can be successfully ablated. As the ablation method is not curative and there remains the risk of dying suddenly in patients with depressed left ventricular ejection fraction, the majority of patients with VT associated with structural heart disease also receive an ICD.