Effect of metoprolol and d,l-sotalol on microvolt-level T-wave alternans Results of a prospective, double-blind, randomized study

AbstractOBJECTIVESThe study evaluated the effects of metoprolol, a pure beta-blocker, and d,l-sotalol, a beta-blocker with additional class III antiarrhythmic effects, on microvolt-level T-wave alternans (TWA).BACKGROUNDAssessment of TWA is increasingly used for purposes of risk stratification in patients prone to sudden death. There are only sparse data regarding the effects of beta-blockers and antiarrhythmic drugs on TWA.METHODSPatients with a history of documented or suspected malignant ventricular tachyarrhythmias were eligible. All patients underwent invasive electrophysiologic (EP) testing including programmed ventricular stimulation and determination of TWA at increasing heart rates using atrial pacing. Reproducibility of TWA at two consecutive drug-free baseline measurements was tested in a random patient subset. Following baseline measurements, all patients were randomized either to double-blind intravenous infusion of sotalol (1.0 mg/kg) or metoprolol (0.1 mg/kg). Results of TWA assessment at baseline and after drug exposure were compared.RESULTSFifty-four consecutive patients were studied. In 12 patients, repetitive baseline measurement of TWA revealed stable alternans voltage (Valt) values (9.1 ± 5.8 μV vs. 8.5 ± 5.7 μV, p = NS). After drug administration, Valtdecreased by 35% with metoprolol (7.9 ± 6.0 μV to 4.9 ± 4.2 μV; p < 0.001) and by 38% with sotalol (8.6 ± 6.8 μV to 4.4 ± 2.3 μV; p = 0.001). In eight patients with positive TWA at baseline, repeated measurement revealed negative test results.CONCLUSIONSIn patients prone to sudden cardiac death, there is a reduction in TWA amplitude following the administration of antiadrenergic drugs. This result indicates that TWA is responsive to the pharmacologic milieu and suggests that, to assess a patient’s risk of spontaneous ventricular arrhythmia, the patient should be tested while maintaining the pharmacologic regimen under which the risk of arrhythmia is being assessed. This applies particularly for beta-blocker therapy

787-5 Systemic Effect of Ramipril on Endothelin, but not on Elcosanoid Levels in Patients with Coronary Artery Disease

Study aimNeurohumoral effects of ramipril (R) alone or in combination with isosorbide dinitrate (ISDN) compared to ISDN or placebo.Study designPlacebo-controlled double-blind parallel group trial.Methods32 patients with coronary artery disease (CAD) received placebo, R5mg, ISDN 20mg slow release b.i.d. or R+ISDN for one week. A 24 hour kinetic profile of ramipril and its metabolite, of ace activity (ACE-A) and of related hormones (renin and aldosterone), of endothelin and of prostaglandins (PG), thromboxane B2 (TXB2), PGF2a, 6-keto PGF1a, the stable metabolite of prostacyclin (PGI2-M) was studied after the first dose. Measurements were repeated after 8 days of treatment before and 3 hours after the morning dose.ResultsHormone measurements are presented as means of percent difference of patients treated with R (n=16) vs. those without ace-inhibitor (n=16).Time (hrs)0123468240–83–8Ramipril (mg/l)08543210.417Ramiprilat (mg/l)0611108751214ACE-A (%)-6-78-95-98-98-97-96-80-82-98Aldosteron (%)9-5-31-34-21-27-23-34--Renin (%)-9-771913175332--Endothelin (%)-17-13-25-19-16-15-40--TXB2 (%)41045-5012-3PGF2a (%)101700-8-22-9PGI2-M (%)70-38--59-1-713-=not done; significant differences are printed in italics (two-tailed t-test)A single oral dose of 5mg R reduced ACE activity (p&lt;0.001), decreased aldosterone and increased renin (p&lt;0.1). R did not influence plasma levels of the vasoconstricting (TXB2, PGF2a) or vasodilating (PGI2-M) eicosanoid mediators, but decreased endothelin (p&lt;0.1).ConclusionR, in a dose that results in significant systemic inhibition of the renin angiotensin aldosteron system, does not induce measurable changes of circulating eicosanoid concentrations, but seems to diminish systemic release of endothelin

Programmed inappropriate ICD ventricular defibrillation for cardioversion of persistent atrial fibrillation

In this report we briefly describe a patient with a dual chamber implantable cardioverter defibrillator in the context of severe ischemic cardiomyopathy who developed persistent atrial fibrillation. After appropriate anticoagulation and under mild sedation the patient was successfully cardioverted to sinus rhythm after a programmed ventricular synchronized defibrillation using his defibrillator. Programmed internal cardioversion of persistent atrial fibrillation in patients who have an implantable cardioverter defibillator without atrial defibrillation capabilities could be an effective and safe therapeutic option. Unlike external electrical cardioversion, this strategy does not interfere with the implantable cardioverter defibrillator, is more effective, and obviates the need of general anesthesia. This strategy should be further evaluated in clinical trials

Atrioventricular junction ablation in patients with atrial fibrillation treated with cardiac resynchronization therapy:Positive impact on ventricular arrhythmias, implantable cardioverter-defibrillator therapies and hospitalizations

Aims: We sought to determine whether atrioventricular junction ablation (AVJA) in patients with cardiac resynchronization therapy (CRT) implantable cardioverter-defibrillator (ICD) and with permanent atrial fibrillation (AF) has a positive impact on ICD shocks and hospitalizations compared with rate-slowing drugs. Methods and results: This is a pooled analysis of data from 179 international centres participating in two randomized trials and one prospective observational research. The co-primary endpoints were all-cause ICD shocks and all-cause hospitalizations. Out of 3358 CRT-ICD patients (2720 male, 66.6years), 2694 (80%) were in sinus rhythm (SR) and 664 (20%) had permanent AF-262 (8%) treated with AVJA (AF+AVJA) and 402 (12%) treated with rate-slowing drugs (AF+Drugs). Median follow-up was 18months. The mean (95% confidence intervals) annual rate of all-cause ICD shocks per 100 patient years was 8.0 (5.3-11.9) in AF+AVJA, 43.6 (37.7-50.4) in AF+Drugs, and 34.4 (32.5-36.5) in SR patients, resulting in incidence rate ratio (IRR) reductions of 0.18 (0.10-0.32) for AF+AVJA vs. AF+Drugs (P<0.001) and 0.48 (0.35-0.66) for AF+AVJA vs. SR (P<0.001). These reductions were driven by significant reductions in both appropriate ICD shocks [IRR 0.23 (0.13-0.40), P<0.001, vs. AF+Drugs] and inappropriate ICD shocks [IRR 0.09 (0.04-0.21), P<0.001, vs. AF+Drugs]. Annual rate of all-cause hospitalizations was significantly lower in AF+AVJA vs. AF+Drugs [IRR 0.57 (0.41-0.79), P<0.001] and SR [IRR 0.85 (073-0.98), P=0.027]. Conclusion: In AF patients treated with CRT, AVJA results in a lower incidence and burden of all-cause, appropriate and inappropriate ICD shocks, as well as to fewer all-cause and heart failure hospitalizations

Atrial fibrillation and heart failure: Factors influencing the choice of oral anticoagulant.

Atrial fibrillation (AF) and heart failure (HF) frequently coexist. AF is identified in approximately one third of patients with HF and is linked to increased morbidity and mortality than from either condition alone. AF is relatively more common in HF with preserved ejection fraction (HFpEF) than with reduced ejection fraction (HFrEF). Nevertheless, the risk of stroke and systemic embolism (SSE) is significantly increased with both HF types and the absolute risk is heavily influenced by the presence and severity of associated additional stroke risk factors. The European Society of Cardiology has very recently introduced a third HF subtype entitled HF with mid-range ejection fraction (HFmrEF). At present oral anticoagulation is recommended for all patients with AF and HF, independent of HF type. In addition to warfarin there are currently four non-vitamin K oral anticoagulants (NOACs, previously called novel oral anticoagulants) that have been approved for the prevention of SSE. They consist of one direct thrombin inhibitor, dabigatran and three factor Xa inhibitors: rivaroxaban, apixaban and, most recently, edoxaban. In this review article we present an overview of the evidence to support the use of NOACs for the prevention of SSE in patients with AF and HF and review the influence of HF subtype and co-morbidities on the potential choice of oral anticoagulant