Guy Amit

Selective Molecular Potassium Channel Blockade Prevents Atrial Fibrillation

Background— Safety and efficacy limit currently available atrial fibrillation (AF) therapies. We hypothesized that atrial gene transfer would allow focal manipulation of atrial electrophysiology and, by eliminating reentry, would prevent AF. Methods and Results— In a porcine AF model, we compared control animals to animals receiving adenovirus that encoded KCNH2-G628S, a dominant negative mutant of the IKr potassium channel &agr;-subunit (G628S animals). After epicardial atrial gene transfer and pacemaker implantation for burst atrial pacing, animals were evaluated daily for cardiac rhythm. Electrophysiological and molecular studies were performed at baseline and when animals were euthanized on either postoperative day 7 or 21. By day 10, none of the control animals and all of the G628S animals were in sinus rhythm. After day 10, the percentage of G628S animals in sinus rhythm gradually declined until all animals were in AF by day 21. The relative risk of AF throughout the study was 0.44 (95% confidence interval 0.33 to 0.59, P<0.01) among the G628S group versus controls. Atrial monophasic action potential was considerably longer in G628S animals than in controls at day 7, and KCNH2 protein levels were 61% higher in the G628S group than in control animals (P<0.01). Loss of gene expression at day 21 correlated with loss of action potential prolongation and therapeutic efficacy. Conclusions— Gene therapy with KCNH2-G628S eliminated AF by prolonging atrial action potential duration. The effect duration correlated with transgene expression.

Microvolt T-wave alternans and electrophysiologic testing predict distinct arrhythmia substrates: Implications for identifying patients at risk for sudden cardiac death

BACKGROUND Better risk stratification of patients receiving an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden cardiac death (SCD) is needed. Although microvolt T-wave alternans (MTWA) and electrophysiologic study (EPS) are independent markers for SCD, the Alternans Before Cardioverter Defibrillator (ABCD) trial found the combination to be more predictive than either test alone. OBJECTIVE The purpose of this study was to test the hypothesis that EPS and MTWA measure different elements of the arrhythmogenic substrate and, therefore, predict distinct arrhythmia outcomes. METHODS The ABCD trial enrolled 566 patients with ischemic cardiomyopathy, left ventricular ejection fraction (LVEF) <or=0.40, and nonsustained ventricular tachycardia. All patients underwent both MTWA test and EPS. The performance of MTWA and EPS in predicting stable ventricular tachyarrhythmic events (S-VTEs) versus unstable ventricular tachyarrhythmic events (U-VTEs), defined as either polymorphic ventricular tachycardia or ventricular fibrillation, was analyzed using Kaplan-Meier event rates and the log rank test. RESULTS MTWA and EPS were abnormal in 71% and 39% of patients, respectively. There were 28 S-VTEs and 10 U-VTEs. MTWA was predictive of U-VTEs (event rate 2.7% in abnormals vs 0% in normals, P = .04), whereas EPS was not (1.5% vs 3.2%, P = .55). In contrast, EPS predicted S-VTEs (9.7% vs 2.2%, P <.01), but MTWA did not (5.5% vs 4.4%, P = .57). Whereas the extent of left ventricular contractile dysfunction alone (LVEF <or=0.30 vs LVEF 0.31-0.40) did not predict events, MTWA predicted events better than did EPS in subjects with LVEF <or=0.30. In contrast, EPS predicted events better than did MTWA test in subjects with LVEF >0.30. CONCLUSION The study data suggest that EPS and MTWA identify distinct arrhythmogenic substrates and, when used in combination, may better predict the complex electroanatomic substrates that underlie the risk for SCD.

What Have the New Definition of Acute Myocardial Infarction and the Introduction of Troponin Measurement Done to the Coronary Care Unit

Objective: To assess the impact of the new American College of Cardiology/European Society of Cardiology definition of acute myocardial infarction (AMI) and the introduction of troponin measurement on the coronary care unit (CCU). Methods: This was a retrospective cohort study performed in a tertiary care university hospital. All admissions to the CCU during the year before (period 1, year 2000, n = 1,134) and the year after (period 2, year 2002, n = 1,360) the introduction of troponin measurement and the new AMI definition were studied. We studied baseline characteristics, case load, distribution of admission diagnoses, management and outcome of patients in the two periods. Results: There was a 20% increase in the number of CCU admissions, driven solely by a 141% increase in the burden of non-ST elevation AMI (NSTEMI) (p < 0.01). This increase was not a mere reflection of a change in diagnostic criteria, as the overall burden of non-ST elevation acute coronary syndromes (ACS) (NSTEMI + unstable angina) increased by 46%, suggesting referral of many more patients to the CCU. Despite a 42% increase in the number of angiograms performed, the proportion of ACS patients who had an angiogram declined. AMI patients in period 2 were older and had higher rates of coronary risk factors but had a higher chance of receiving a guideline-based therapy. Length of CCU stay decreased by a whole day for all ACS patients. 30-day mortality for AMI patients did not change significantly. Conclusions: The new AMI definition had a dramatic impact on the CCU case load, case mix and length of stay and on the ability to provide early coronary angiography.

Management of patients with implantable cardioverter-defibrillators and pacemakers who require radiation therapy

BACKGROUND Radiation therapy (RT) may pose acute and long-term risks for patients with cardiac implantable electronic devices (CIEDs), including pacemakers (PMs) and implantable cardioverter-defibrillators (ICDs). However, the frequency of these problems has not been accurately defined. OBJECTIVE The purpose of this study was to determine the prevalence of CIEDs among patients requiring RT and report the common CIED-related problems when patients are managed according to a standard clinical care path. METHODS In a single tertiary-care center, we prospectively screened all patients requiring RT and identified patients with ICDs or PMs. We collected clinical data about their cancer, RT treatment plan, and CIED. Radiation dose to the device was estimated in all patients, and any device malfunction during RT was documented. RESULTS Of the 34,706 consecutive patients receiving RT, 261 patients (0.8%, mean age 77.9 ± 9.4 years) had an implantable cardiac device: 54 (20.7%) ICDs and 207 (79.3%) PMs. The site of RT was head and neck (27.4%), chest (30.0%), and abdomen/pelvis (32.6%). Using our care path, 63.2% of patients required continuous cardiac monitoring, 14.6% required device reprogramming, 18.8% required magnet application during RT, and 3.4% required device repositioning to the contralateral side before RT. Four patients (1.5%) had inappropriate device function during RT: 3 experienced hemodynamically tolerated ventricular pacing at the maximum sensor rate, and 1 experienced a device power-on-reset. No patient died or suffered permanent device failure. CONCLUSION Nearly 1% of patients receiving RT in this series has a PM or ICD. However, with a systematic policy of risk assessment and patient management, significant device-related complications are rare.

B-type natruiretic peptide levels stratify the risk for arrhythmia among implantable cardioverter defibrillator patients.

We sought to study the association between brain natriuretic peptide (BNP) levels and the occurrence of ventricular arrhythmias in patients with left ventricular dysfunction (LVD) and an implantable cardioverter defibrillator (ICD).

Sex differences in implantable cardioverter-defibrillator implantation indications and outcomes: lessons from the Nationwide Israeli-ICD Registry.

AIMS Implantable cardioverter-defibrillators (ICDs) improve survival in certain high arrhythmic risk populations. However, there are sex differences regarding both the utilization and the benefit of these devices. Using a prospective national ICD registry, we aim to compare the indications for ICD implantation as well as outcomes in implanted women vs. men. METHODS AND RESULTS All subjects implanted with an ICD or cardiac resynchronization therapy with a defibrillator (CRTD) in Israel between July 2010 and February 2013 were included. A total of 3544 subjects constructed the baseline cohort, of whom 615 (17%) were women. Women had the same age (64 years) and rate of secondary prevention indication (26%) as men. However, women were more likely than men to have significant heart failure symptoms (52 vs. 45%), QRS > 120 ms (41 vs. 36%), and a higher rate of non-ischaemic cardiomyopathy (54 vs. 21%, all P values <0.05). Using multivariate analysis, women were more likely to undergo CRTD implantation (odds ratio = 1.8, P < 0.01). Follow-up data were available for 1518 subjects with a mean follow-up of 12 months. During follow-up, there were no significant differences among genders in the rate of any single or the combined outcomes of appropriate device therapies, heart failure admissions, or death. First-year re-intervention rate was double among women (5.6 vs. 3.0%, P < 0.01). CONCLUSION In real-world setting, women implanted with an ICD differ significantly from men in their baseline characteristics and in the use of CRTD devices. These, however, did not translate into outcome differences.

Biological therapies for atrial fibrillation.

Atrial fibrillation is a prominent cause of morbidity and mortality in developed countries. Current treatment strategies center on controlling heart rate while allowing fibrillation to persist or targeting fibrillation primarily and attempting to maintain sinus rhythm. Pharmacological therapies are largely successful for rate control, although mild toxicities are common. Rhythm control strategies are often unsuccessful, leaving patients in atrial fibrillation despite attempts to maintain sinus rhythm. This review will discuss novel biological strategies that are currently under development and may eventually have impact on the management of atrial fibrillation.

Atrial Electrical Activity Detection Using Linear Combination of 12-Lead ECG Signals

ECG analysis is the method for cardiac arrhythmia diagnosis. During the diagnostic process many features should be taken into consideration, such as regularity and atrial activity. Since in some arrhythmias, the atrial electrical activity (AEA) waves are hidden in other waves, and a precise classification from surface ECG is inapplicable, a confirmation diagnosis is usually performed during an invasive procedure. In this paper, we study a “semiautomatic” method for AEA-waves detection using a linear combination of 12-lead ECG signals. This methods objective is to be applicable to a variety of arrhythmias with emphasis given to detect concealed AEA waves. It includes two variations--using maximum energy ratio and a synthetic AEA signal. In the former variation, an energy ratio-based cost function is created and maximized using the gradient ascent method. The latter variation adapted the linear combiner method, when applied on a synthetic signal, combined with surface ECG leads. A study was performed evaluating the AEA-waves detection from 63 patients (nine training, 54 validation) presenting eight arrhythmia types. Averaged sensitivity of 92.21% and averaged precision of 92.08% were achieved compared to the definite diagnosis. In conclusion, the presented method may lead to early and accurate detection of arrhythmias, which will result in a better oriented treatment.

Insufficient compliance with current implantable cardioverter defibrillator (ICD) therapy guidelines in post myocardial infarction patients is associated with increased mortality

UNLABELLED Current clinical guidelines advocate implantable cardioverter defibrillator (ICD) therapy for the prevention of sudden cardiac death among post myocardial infarction (MI) patients. However, there are scarce data regarding compliance with the guidelines and utilization of this life-saving treatment. We aimed to assess the rate of ICD utilization among post MI patients with left ventricular ejection fraction (LVEF) ≤ 35%. METHODS All patients admitted with a ST-elevation MI at a single tertiary care center from 2005 to 2009, discharged alive with LVEF≤35% and surviving 40 days were included. Patients already implanted with an ICD and whose residence was outside the hospitals area of coverage were excluded. ICD utilization, LVEF re-assessment and mortality were assessed during mean follow up time of 2 years. RESULTS Of the 285 subjects, only 26 (9%) received an ICD. There were significant differences in ICD use among different medical health organizations (insurers). Among the 259 subjects not implanted with an ICD, repeat echocardiography study for the re-assessment of LVEF was performed in only 176 (68%). Of those, LVEF remained severely impaired in 47%. After excluding subject whose LVEF improved at follow up, the ICD utilization rate was 14%. In a multi-variable analysis, significant predictors of ICD utilization were age below the median of 61 years, and a repeat echocardiography. Using propensity score and matching of subjects implanted with ICD with those not implanted, ICD implantation was found to be associated with survival benefit. CONCLUSIONS ICDs are underutilized in post MI patients and compliance with current guidelines is insufficient. Failure to re-assess LVEF is a barrier for this life-saving treatment. Withholding ICD therapy among unselected post MI patients with depressed LVEF is associated with a markedly increased mortality.

Thrombocytopenia, Immunoglobulin Treatment, and Acute Myocardial Infarction: A Case Report

Platelets play a pivotal role in the pathophysiology of the acute coronary syndromes, and platelet inhibition is a cornerstone in the management of these patients. Patients with profound thrombocytopenia who present with an acute coronary syndrome present a difficult challenge. The authors report a patient with immune thrombocytopenic purpura who presented with acute myocardial infarction despite a very low platelet count and who sustained recurrent infarction after receiving immune globulin treatment. The best management of thrombocytopenic patients with acute coronary syndromes is uncertain, but extreme caution is needed before efforts are made to raise the platelet count in order to allow conventional treatment.