Eric J. Rashba

Influence of Pregnancy on the Risk for Cardiac Events in Patients With Hereditary Long QT Syndrome

BACKGROUND The effects of pregnancy on women with the hereditary long QT syndrome are currently unknown. The appropriate medical management of pregnant patients with the long QT syndrome has not been established. METHODS AND RESULTS The study was a retrospective analysis of the 422 women (111 probands affected with the long QT syndrome and 311 first-degree relatives) enrolled in the long QT syndrome registry who had one or more pregnancies. The first-degree relatives were classified as affected (QTc >0.47), borderline (QTc=0.45 to 0.47), and unaffected (QTc <0.45). Cardiac events were defined as the combined incidence of long QT syndrome-related death, aborted cardiac arrest, and syncope. The incidence of cardiac events was compared during equal prepregnancy, pregnancy, and postpartum intervals (40 weeks each). Multivariate logistic regression analysis was performed by use of a mixed-effects model to identify independent predictors of cardiac events among probands. The pregnancy and postpartum intervals were not associated with cardiac events among first-degree relatives. The postpartum interval was independently associated with cardiac events among probands (odds ratio [OR], 40.8; 95% confidence interval [CI], 3.1 to 540; P=.01); the pregnancy interval was not associated with cardiac events. Treatment with beta-adrenergic blockers was independently associated with a decrease in the risk for cardiac events among probands (OR, 0.023; 95% CI, 0.001 to 0.44; P=.01). CONCLUSIONS The postpartum interval is associated with a significant increase in risk for cardiac events among probands with the long QT syndrome but not among first-degree relatives. Prophylactic treatment with beta-adrenergic blockers should be continued during the pregnancy and postpartum intervals in probands with the long QT syndrome.

Influence of QRS duration on the prognostic value of T wave alternans.

T Wave Alternans and QRS Duration. Introduction: T wave alternans (TWA) is a promising new noninvasive marker of arrhythmia vulnerability that quantifies beat‐to‐beat changes in ventricular repolarization. Secondary repolarization abnormalities are common in subjects with wide QRS complexes. However, the relationship between TWA and QRS prolongation has not been evaluated. The goal of this study was to determine if QRS prolongation influences the prevalence or prognostic value of TWA.

Novel use of atrial overdrive pacing to rapidly differentiate junctional tachycardia from atrioventricular nodal reentrant tachycardia

BACKGROUND Distinguishing between junctional tachycardia (JT) and atrioventricular nodal reentrant tachycardia (AVNRT) is essential to minimize unnecessary catheter ablation and the risk of heart block during treatment of AVNRT. OBJECTIVE The purpose of this study was to investigate whether the tachycardia response to atrial overdrive pacing at a cycle length (CL) slightly shorter than tachycardia CL can differentiate between JT and AVNRT. We hypothesized that atrial overdrive pacing would transiently suppress JT but would entrain AVNRT. METHODS Twenty-one patients in whom AVNRT was induced and atrial overdrive pacing during either AVNRT or JT was attempted were included in the study. We predicted that, upon cessation of atrial overdrive pacing, an atrial-His-His-atrial (AHHA) response would identify JT and an atrial-His-atrial (AHA) response would identify AVNRT. RESULTS A total of 8 JT and 21 typical AVNRT were induced. Atrial overdrive pacing was attempted in all cases of JT and in 16 cases of AVNRT. An AHHA response was observed in 100% (8/8) of JT cases. In 2 cases of AVNRT, atrial overdrive pacing repetitively terminated the tachycardia. In the remaining patients with AVNRT, an AHA response was observed in 100% (14/14) of cases. When a response was able to be elicited, atrial overdrive pacing was 100% sensitive and 100% specific for differentiating JT from AVNRT. CONCLUSION Atrial overdrive pacing during tachycardia can rapidly differentiate JT from AVNRT, which can improve the safety and efficiency of catheter ablation of these arrhythmias.

Electrophysiological Effects of Late Percutaneous Coronary Intervention for Infarct-Related Coronary Artery Occlusion The Occluded Artery Trial-Electrophysiological Mechanisms (OAT-EP)

Background— The Occluded Artery Trial–Electrophysiological Mechanisms (OAT-EP) tested the hypothesis that opening a persistently occluded infarct-related artery by percutaneous coronary intervention and stenting (PCI) after the acute phase of myocardial infarction compared with optimal medical therapy alone reduces markers of vulnerability to ventricular arrhythmias. Methods and Results— Between April 2003 and December 2005, 300 patients with an occluded native infarct-related artery 3 to 28 days (median, 12 days) after myocardial infarction were randomized to PCI or optimal medical therapy. Ten-minute digital Holter recordings were obtained before randomization, at 30 days, and at 1 year. The primary end point was the change in &agr;1, a nonlinear heart rate variability parameter, between baseline and 1 year. Major secondary end points were the changes in the filtered QRS duration on the signal-averaged ECG and variability in T-wave morphology (T-wave variability) between baseline and 1 year. There were no significant differences in the changes in &agr;1 (−0.04; 95% CI, −0.12 to 0.04), filtered QRS (2.2 ms; 95% CI, −1.4 to 5.9 ms), or T-wave variability (3.0 &mgr;V; 95% CI, −4.8 to 10.7 &mgr;V) between the PCI and medical therapy groups (medical therapy change minus PCI change). Multivariable analysis revealed that the results were unchanged after adjustment for baseline clinical variables and medication treatments during the Holter recordings. Conclusions— PCI with stenting of a persistently occluded infarct-related artery during the subacute phase after myocardial infarction compared with medical therapy alone had no significant effect on changes in heart rate variability, the time-domain signal-averaged ECG, or T-wave variability during the first year after myocardial infarction. These findings are consistent with the lack of clinical benefit, including no reduction in sudden death, with PCI for stable patients with persistently occluded infarct-related arteries after myocardial infarction in the main OAT.

Study design for the Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency Care (IMMEDIATE) Trial: A double-blind randomized controlled trial of intravenous glucose, insulin, and potassium for acute coronary syndromes in emergency medical services.

BACKGROUND Experimental studies suggest that metabolic myocardial support by intravenous (IV) glucose, insulin, and potassium (GIK) reduces ischemia-induced arrhythmias, cardiac arrest, mortality, progression from unstable angina pectoris to acute myocardial infarction (AMI), and myocardial infarction size. However, trials of hospital administration of IV GIK to patients with ST-elevation myocardial infarction (STEMI) have generally not shown favorable effects possibly because of the GIK intervention taking place many hours after ischemic symptom onset. A trial of GIK used in the very first hours of ischemia has been needed, consistent with the timing of benefit seen in experimental studies. OBJECTIVE The IMMEDIATE Trial tested whether, if given very early, GIK could have the impact seen in experimental studies. Accordingly, distinct from prior trials, IMMEDIATE tested the impact of GIK (1) in patients with acute coronary syndromes (ACS), rather than only AMI or STEMI, and (2) administered in prehospital emergency medical service settings, rather than later, in hospitals, after emergency department evaluation. DESIGN The IMMEDIATE Trial was an emergency medical service-based randomized placebo-controlled clinical effectiveness trial conducted in 13 cities across the United States that enrolled 911 participants. Eligible were patients 30 years or older for whom a paramedic performed a 12-lead electrocardiogram to evaluate chest pain or other symptoms suggestive of ACS for whom electrocardiograph-based acute cardiac ischemia time-insensitive predictive instrument indicated a ≥75% probability of ACS, and/or the thrombolytic predictive instrument indicated the presence of a STEMI, or if local criteria for STEMI notification of receiving hospitals were met. Prehospital IV GIK or placebo was started immediately. Prespecified were the primary end point of progression of ACS to infarction and, as major secondary end points, the composite of cardiac arrest or in-hospital mortality, 30-day mortality, and the composite of cardiac arrest, 30-day mortality, or hospitalization for heart failure. Analyses were planned on an intent-to-treat basis, on a modified intent-to-treat group who were confirmed in emergency departments to have ACS, and for participants presenting with STEMI. CONCLUSION The IMMEDIATE Trial tested whether GIK, when administered as early as possible in the course of ACS by paramedics using acute cardiac ischemia time-insensitive predictive instrument and thrombolytic predictive instrument decision support, would reduce progression to AMI, mortality, cardiac arrest, and heart failure. It also tested whether it would provide clinical and pathophysiologic information on GIKs biological mechanisms.

Temporal decline in defibrillation thresholds with an active pectoral lead system

OBJECTIVES The objective of this study was to characterize temporal changes in defibrillation thresholds (DFTs) after implantation with an active pectoral, dual-coil transvenous lead system. BACKGROUND Ventricular DFTs rise over time when monophasic waveforms are used with non-thoracotomy lead systems. This effect is attenuated when biphasic waveforms are used with transvenous lead systems; however, significant increases in DFT still occur in a minority of patients. The long-term stability of DFTs with contemporary active pectoral lead systems is unknown. METHODS This study was a prospective assessment of temporal changes in DFT using a uniform testing algorithm, shock polarity and dual-coil active pectoral lead system. Thresholds were measured at implantation, before discharge and at long-term follow-up (70 +/- 40 weeks) in 50 patients. RESULTS The DFTs were 9.2 +/- 5.4 J at implantation, 8.3 +/- 5.8 J before discharge and 6.9 +/- 3.6 J at long-term follow-up (p < 0.01 by analysis of variance; p < 0.05 for long-term follow-up vs. at implantation or before discharge). The effect was most marked in a prespecified subgroup with high implant DFTs (> or =15 J). No patient developed an inadequate safety margin (< 9 J) during follow-up. CONCLUSIONS The DFTs declined significantly after implantation with an active pectoral, dual-coil transvenous lead system, and no clinically significant increases in DFT were observed. Therefore, routine defibrillation testing may not be required during the first two years after implantation with this lead system, in the absence of a change in the cardiac substrate or treatment with antiarrhythmic drugs.

Effect of shock polarity on defibrillation thresholds with a hybrid patch-coil lead system.

AbstractIntroduction: Understanding the factors that affect defibrillation thresholds (DFTs) has important implications both for optimization of defibrillation efficacy and for the design of new lead systems. The objective of this prospective study was to evaluate the effect of shock polarity on defibrillation efficacy at the time of routine pulse generator replacement in patients with a hybrid patch-coil lead system. Methods: Each patient underwent 4 assessments of DFT: monophasic or biphasic shock with standard or reversed polarity, with the order of testing with respect to polarity randomized. In standard polarity, the right atrial coil is the anode and the left ventricular patch is the cathode. Results: The study population of 30 patients was 80% men with a mean age of 65 ± 9 years and a mean left ventricular ejection fraction of 33 ± 12%. There was a significant 21% decrease in the mean monophasic DFT with reversed polarity shocks (13.1 ± 5.9 J vs. 16.6 ± 6.5 J, p < 0.01). Reversal of shock polarity did not have a significant effect on the mean biphasic DFT (8.0 ± 4.8 J vs. 8.5 ± 4.3 J for reversed and standard polarity respectively, p = NS). However, when an elevated biphasic DFT (≥15 J) was present in either standard or reversed polarity, a significant decrease in DFT was observed when the opposite polarity was used (16.7 ± 2.5 J vs. 9.1 ± 2.7 J, n = 9, p < 0.0001). Conclusion: Reversal of shock polarity markedly improves monophasic DFTs with the patch-coil lead configuration. The DFT should be determined with both shock polarities to optimize defibrillation efficacy for patients with high biphasic DFTs (≥15 J).

Anger Management May Save Your Life : New Insights Into Emotional Precipitants of Ventricular Arrhythmias

Sudden cardiac arrest is a leading cause of mortality, accounting for over 400,000 deaths annually in the U.S. alone ([1][1]). Most sudden cardiac arrests are due to ventricular tachycardia or ventricular fibrillation ([1][1]). Given the dismal survival statistics for out-of-hospital sudden cardiac

Very early administration of glucose-insulin-potassium by emergency medical service for acute coronary syndromes: Biological mechanisms for benefit in the IMMEDIATE Trial

AIMS In the IMMEDIATE Trial, intravenous glucose-insulin-potassium (GIK) was started as early as possible for patients with suspected acute coronary syndrome by ambulance paramedics in communities. In the IMMEDIATE Biological Mechanism Cohort substudy, reported here, we investigated potential modes of GIK action on specific circulating metabolic components. Specific attention was given to suppression of circulating oxygen-wasting free fatty acids (FFAs) that had been posed as part of the early GIK action related to averting cardiac arrest. METHODS We analyzed the changes in plasma levels of FFA, glucose, C-peptide, and the homeostasis model assessment (HOMA) index. RESULTS With GIK, there was rapid suppression of FFA levels with estimated levels for GIK and placebo groups after 2 hours of treatment of 480 and 781 μmol/L (P<.0001), even while patterns of FFA saturation remained unchanged. There were no significant changes in the HOMA index in the GIK or placebo groups (HOMA index: placebo 10.93, GIK 12.99; P = .07), suggesting that GIK infusions were not countered by insulin resistance. Also, neither placebo nor GIK altered endogenous insulin secretion as reflected by unchanging C-peptide levels. CONCLUSION These mechanistic observations support the potential role of FFA suppression in very early cardioprotection by GIK. They also suggest that the IMMEDIATE Trial GIK formula is balanced with respect to its insulin and glucose composition, as it induced no endogenous insulin secretion.

Conversational Atrial Tachycardia

![Figure][1] [![Graphic][3] ][3] A 63-year-old man with history of paroxysmal atrial fibrillation presented with symptoms of dyspnea and dizziness for several weeks. Curiously, these symptoms occurred only while he was speaking. Electrocardiography revealed paroxysms of atrial