Effects of GLP-1 Agonists on mortality and arrhythmias in patients with Type II diabetes.

Background: Glucagon-like Peptide-1 Receptor Agonists (GLP-1 RA) are frequently used for the management of diabetes. The impact of GLP-1 RA on cardiovascular outcomes is unclear. We aim to assess the effect of GLP-1 RA on mortality, atrial and ventricular arrhythmias, and sudden cardiac death in patients with type II diabetes. Methods: We searched databases including Ovid MEDLINE, EMBASE, Scopus, Web of Science, Google Scholar and CINAHL, from inception to May 2022, for randomized controlled trials reporting the relationship between GLP-1 RA (including albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, and semaglutide) and mortality, atrial arrhythmias, and the combined incidence of ventricular arrhythmias and sudden cardiac death. The search was not restricted to time or publication status. Results: A total of 464 studies resulted from literature search, of which 44 studies, including 78,702 patients (41,800 GLP-1 agonists vs 36,902 control), were included. Follow up ranged from 52 to 208 weeks. GLP-1 RA were associated with lower risk of all-cause mortality (odds ratio 0.891, 95% confidence interval 0.837-0.949; P < 0.01) and reduced cardiovascular mortality (odds ratio 0.88, 95% confidence interval 0.881-0.954; P < 0.01). GLP-1 RA were not associated with increased risk of atrial (odds ratio 0.963, 95% confidence interval 0.869-1.066; P 0.46) or ventricular arrhythmias and sudden cardiac death (odds ratio 0.895, 95% confidence interval 0.706-1.135; P 0.36). Conclusion: GLP-1 RA are associated with decreased all-cause and cardiovascular mortality, and no increased risk of atrial and ventricular arrhythmias and sudden cardiac death.

Effect of Implanted Defibrillator on Mortality in Patients With Chronic Kidney Disease.

The beneficial role of implantable cardioverter defibrillators (ICDs) in patients with chronic kidney disease (CKD) is controversial. This meta-analysis aimed to evaluate the effect of ICD on mortality in patients with CKD. A literature search was conducted for studies reporting the effect of ICD on all-cause mortality in patients with CKD (estimated glomerular filtration rate <60 ml/min/1.73 m2). The search was not restricted to time or publication status. The search included the following databases: Ovid MEDLINE, EMBASE, Scopus, Web of Science, Google Scholar, and EBSCO CINAHL. The primary end point was all-cause mortality. The minimum duration of follow-up required for inclusion was 1 year. The literature search identified 834 studies, of which 14 studies with 70,661 patients were included. Mean follow-up was 39 months (12 to 81 months). For all patients with CKD, ICD was associated with lower all-cause mortality (log hazard ratio [HR] -0.247, standard error [SE] 0.101, p = 0.015). Heterogeneity: degree of freedom = 13 (p <0.01), I2 = 97.057; test for overall effect: Z = -2.431 (p = 0.015). When further stratified based on dialysis, patients with CKD without the need for dialysis had significantly lower mortality (log HR -0.211, SE 0.095, p = 0.026), with a similar trend in patients who underwent dialysis (log HR -0.262, SE 0.134, p = 0.051). ICD implantation is associated with a significant mortality benefit in patients with CKD.

Electrical Storm in a Case of Bilateral Pheochromocytomas.

BACKGROUND Pheochromocytomas are catecholamine-secreting tumors that develop within the chromaffin cells of the adrenal glands. They most commonly present with hypertension, and the classic triad of symptoms is headaches, palpitations, and diaphoresis. Electrical storm (ES) is defined as at least 3 sustained episodes of ventricular tachycardia (VT), ventricular fibrillation (VF), or appropriate shocks from an implanted cardioverter-defibrillator (ICD) within 24 h. We discuss the case of a 63-year-old man with known bilateral pheochromocytomas who presented with ES prompting multiple ICD shocks, possibly exacerbated by catecholamine surge from his adrenal tumors. CASE REPORT The patient was a 63-year-old man with an extensive medical history including ischemic cardiomyopathy and congestive heart failure with reduced ejection fraction presented with multiple syncopal episodes secondary to persistent monomorphic ventricular tachycardia (MMVT), polymorphic ventricular tachycardia (PMVT), and VF requiring ICD shocks. He had known bilateral pheochromocytomas. ES was attributed to catecholamine excess in the setting of these tumors, so VT ablation was deferred pending tumor removal. Alpha blockade was initiated preoperatively, and the patient subsequently underwent bilateral adrenalectomy; however, he continued to sustain tachyarrhythmias and eventually died despite resuscitative efforts. CONCLUSIONS Bilateral pheochromocytomas are rare adrenal tumors. In even more infrequent situations, they can cause ES secondary to adrenergic stimulation from catecholamine surges. It is worth considering pheochromocytoma in patients with refractory ES, as treating these tumors could potentially reduce the frequency of this dangerous arrhythmia.

Syncope, seizure or both?

Ictal asystole (IA) is a rare phenomenon in patients with seizures with an incidence of 0.27-0.4% and has been proposed as a possible mechanism of sudden unexpected death in epilepsy patients (SUDEP). We present a case of a 53-year-old woman who initially presented with episodes of expressive aphasia and was treated with antiepileptic drugs (AEDs). While on therapy she experienced episodes of syncope. During her hospitalization for tapering of AEDs and 24-hour EEG monitoring, the patient developed a seizure followed by sinus bradycardia and an 18-second sinus pause, resulting in loss of consciousness and slowing of cerebral activity. Ten seconds after the return of cardiac activity, the EEG showed return of cerebral activity. A dual chamber pacemaker was implanted.

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.

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 GIK's biological mechanisms.

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 alpha1, 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 alpha1 (-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 microV; 95% CI, -4.8 to 10.7 microV) 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.

When, how, and why should sinus rhythm be restored in patients with persistent atrial fibrillation?

The results of the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) trial indicate that the rate control strategy is preferred for the majority of patients with paroxysmal and persistent atrial fibrillation (AF). If the patient remains symptomatic despite adequate rate control or if rate control cannot be achieved, then rhythm control therapies are indicated. The most likely explanation for the disappointing results of the AFFIRM trial is the poor efficacy and excessive toxicity of rhythm control medications, because the presence of sinus rhythm was associated with a favorable prognosis in AFFIRM. As a result, there is currently great interest in nonpharmacologic therapies such as AF ablation and development of new drugs for AF with a more favorable efficacy and toxicity profile. AF ablation should be reserved for patients who fail an initial trial of a rhythm control medication until additional clinical trial information is available to justify the use of AF ablation as first-line therapy. When rhythm control therapy is indicated, the choice of antiarrhythmic medication should be dictated by the presence or absence of structural heart disease, congestive heart failure, renal dysfunction, or other comorbidities in order to maximize efficacy and minimize the chance of proarrhythmia or extracardiac toxicity.

Effect of an active abdominal pulse generator on defibrillation thresholds with a dual-coil, transvenous ICD lead system.

INTRODUCTION: Many patients with implantable cardioverter defibrillators (ICDs) have older lead systems, which are usually not replaced at the time of pulse generator replacement unless a malfunction is noted. Therefore, optimization of defibrillation with these lead systems is clinically important. The objective of this prospective study was to determine if an active abdominal pulse generator (Can) affects chronic defibrillation thresholds (DFTs) with a dual-coil, transvenous ICD lead system. METHODS AND RESULTS: The study population consisted of 39 patients who presented for routine abdominal pulse generator replacement. Each patient underwent two assessments of DFT using a step-down protocol, with the order of testing randomized. The distal right ventricular (RV) coil was the anode for the first phase of the biphasic shocks. The proximal superior vena cava (SVC) coil was the cathode for the Lead Alone configuration (RV --> SVC). For the Active Can configuration, the SVC coil and Can were connected electrically as the cathode (RV --> SVC + Can). The Active Can configuration was associated with a significant decrease in shock impedance (39.5 +/- 5.8 Omega vs. 50.0 +/- 7.6 Omega, P < 0.01) and a significant increase in peak current (8.3 +/- 2.6 A vs. 7.2 +/- 2.4 A, P < 0.01). There was no significant difference in DFT energy (9.0 +/- 4.6 J vs. 9.8 +/- 5.2 J) or leading edge voltage (319 +/- 86 V vs. 315 +/- 83 V). An adequate safety margin for defibrillation (> or =10 J) was present in all patients with both shocking configurations. CONCLUSION: DFTs are similar with the Active Can and Lead Alone configurations when a dual-coil, transvenous lead is used with a left abdominal pulse generator. Since most commercially available ICDs are only available with an active can, our data support the use of an active can device with this lead system for patients who present for routine pulse generator replacement.

Coronary sinus electrode does not reduce atrial defibrillation thresholds.

BACKGROUND: Atrial defibrillation can be achieved with a conventional dual-coil, active pectoral implantable cardioverter-defibrillator (ICD) lead system. Shocking vectors that incorporate an additional electrode in the CS have been used, but it is unclear if they improve atrial DFTs. OBJECTIVE: The objective of this prospective, randomized study was to determine if a coronary sinus (CS) electrode reduces atrial defibrillation thresholds (DFTs). METHODS: This was a prospective study of 36 patients undergoing initial ICD implant for standard indications. A defibrillation lead with superior vena cava (SVC) and right ventricular (RV) shocking coils was implanted in the RV. An active can emulator (Can) was placed in a pre-pectoral pocket. A lead with a 4 cm long shocking coil was placed in the CS. Atrial DFTs were determined in the following 3 shocking configurations in each patient, with the order of testing randomized: RV --> SVC + Can (Ventricular Triad), distal CS --> SVC + Can (Distal Atrial Triad), and proximal CS --> SVC + Can (Proximal Atrial Triad). RESULTS: The Proximal and Distal Atrial Triad configurations were both associated with significant reductions in peak current (p < 0.01), but this effect was offset by significant increases in shock impedance (p < 0.01), resulting in no net change in the peak voltage or DFT energy in comparison to the Ventricular Triad configuration (Ventricular Triad: 4.9 +/- 6.6 J, Proximal Atrial Triad: 3.3 +/- 4.1J, Distal Atrial Triad: 4.4 +/- 6.7 J, p > 0.2). CONCLUSION: Shocking vectors that incorporate a CS coil do not significantly improve atrial defibrillation efficacy. Since the Ventricular Triad shocking pathway provides reliable atrial and ventricular defibrillation, this configuration should be preferred for combined atrial and ventricular ICDs.