The effect of ICD programming on inappropriate and appropriate ICD Therapies in ischemic and nonischemic cardiomyopathy: the MADIT-RIT trial.

INTRODUCTION: The MADIT-RIT trial demonstrated reduction of inappropriate and appropriate ICD therapies and mortality by high-rate cut-off and 60-second-delayed VT therapy ICD programming in patients with a primary prophylactic ICD indication. The aim of this analysis was to study effects of MADIT-RIT ICD programming in patients with ischemic and nonischemic cardiomyopathy. METHODS AND RESULTS: First and total occurrences of both inappropriate and appropriate ICD therapies were analyzed by multivariate Cox models in 791 (53%) patients with ischemic and 707 (47%) patients with nonischemic cardiomyopathy. Patients with ischemic and nonischemic cardiomyopathy had similar incidence of first inappropriate (9% and 11%, P = 0.21) and first appropriate ICD therapy (11.6% and 14.1%, P = 0.15). Patients with ischemic cardiomyopathy had higher mortality rate (6.1% vs. 3.3%, P = 0.01). MADIT-RIT high-rate cut-off (arm B) and delayed VT therapy ICD programming (arm C) compared with conventional (arm A) ICD programming were associated with a significant risk reduction of first inappropriate and appropriate ICD therapy in patients with ischemic and nonischemic cardiomyopathy (HR range 0.11-0.34, P < 0.001 for all comparisons). Occurrence of total inappropriate and appropriate ICD therapies was significantly reduced by high-rate cut-off ICD programming and delayed VT therapy ICD programming in both ischemic and nonischemic cardiomyopathy patients. CONCLUSION: High-rate cut-off and delayed VT therapy ICD programming are associated with significant reduction in first and total inappropriate and appropriate ICD therapy in patients with ischemic and nonischemic cardiomyopathy.

Electroatriography - time-frequency analysis of atrial fibrillation from modified 12-lead ECG configurations for improved diagnosis and therapy.

Current atrial fibrillation (AF) management guidelines suggest that initially a decision must be made to apply either a rate control or rhythm control strategy in the individual patient. However, patients' selection remains substantially empirical and the strategy initially chosen often proves unsuccessful and alternative therapies must be adopted. Thus, it seems desirable to develop and apply tests that quantify AF disease state and guide AF management. The overall hypothesis of this paper is that time-frequency analysis of AF from modified 12-lead ECG configurations will improve AF management beyond current diagnostic and therapeutic standards. In particular, we present a novel concept in which 12-lead ECG configurations are modified for time-frequency analysis of AF (electroatriography). While five electrodes (VR, VL, VF, V1, V2) are placed in the conventional position, the other four electrodes (V3, V4, V5, V6) are empirically repositioned anterior or posterior over the atria. By applying spatiotemporal QRST cancellation and time-frequency analysis to these recordings in 19 patients with persistent AF, fibrillatory rate dispersion among individual anterior (25+/-14 fibrillations per minute, fpm) and posterior leads (16+/-11fpm) as well as individual anterior/posterior rate gradients ranging between -24 and +116fpm could be identified. Consequently, the portrayed techniques may form the conceptual basis for individualized noninvasive characterization of AF. Initiation of further studies using the described techniques in different AF subsets, for comparisons with intracardiac recordings and outcome of different therapies, e.g. cardioversion, antiarrhythmic drug and ablation therapy may be stimulated.

Aortic thrombus and pulmonary embolism in a patient with hyperhomocysteinemia.

BACKGROUND: A 32-year-old man presented at hospital with persistent pain, hypothermia and paraesthesia in his right leg, caused by embolic occlusion of all three large arteries as a result of massive thrombi in the abdominal aorta. Previously, the patient had been diagnosed with pulmonary embolism and admitted at least a 6-month history of alcohol abuse. Laboratory assessment of the patient's lipid levels, platelet function and coagulation factors yielded normal results. Duplex ultrasound revealed substantial media thickening of the carotid and femoral arteries, without evidence of calcification. Further laboratory tests revealed elevated plasma levels of homocysteine, asymmetric dimethylarginine, symmetric dimethylarginine and 8-isoprostaglandin F2alpha. INVESTIGATIONS: Physical examination, laboratory analyses, bronchoscopy, duplex ultrasonography, CT scan and CT angiography. DIAGNOSIS: Severe hyperhomocysteinemia associated with acute aortic thrombi and peripheral emboli. MANAGEMENT: Diet supplementation with folic acid, vitamin B6 and vitamin B12, low-molecular-weight heparin and L-arginine.

Pilot study: Noninvasive monitoring of oral flecainide's effects on atrial electrophysiology during persistent human atrial fibrillation using the surface electrocardiogram.

BACKGROUND: The relation between flecainide's plasma level and its influence on human atrial electrophysiology during acute and maintenance therapy of atrial fibrillation (AF) is unknown. Therefore, this study determined flecainide plasma levels and atrial fibrillatory rate obtained from the surface ECG during initiation and early maintenance of oral flecainide in patients with persistent lone AF and assessed their relationship. METHODS AND RESULTS: In 10 patients (5 males, mean age 63 +/- 14 years, left atrial diameter 46 +/- 3 mm) with persistent lone AF, flecainide was administered as a single oral bolus (day 1) followed by 200-400 mg/day (days 2-5). The initial 300 mg flecainide bolus resulted in therapeutic plasma levels in all patients (range 288-629 ng/ml) with no side effects. Flecainide plasma levels increased on day 3 and remained stable thereafter. Day 5 plasma levels were lower (508 +/- 135 vs 974 +/- 276 ng/ml, P = 0.009) in patients with daily mean flecainide doses of 200 mg compared to patients with higher maintenance doses. Fibrillatory rate obtained from the surface electrocardiogram measuring 378 +/- 17 fpm at baseline was reduced to 270 +/- 18 fpm (P < 0.001) after the flecainide bolus but remained stable thereafter. Fibrillatory rate reduction was independent of flecainide plasma levels or clinical variables. CONCLUSION: A 300 mg oral flecainide bolus is associated with electrophysiologic effects that are not increased during early maintenance therapy in persistent human lone AF. In contrast to drug plasma levels, serial analysis of fibrillatory rate allows monitoring of individual drug effects on atrial electrophysiology.

T wave alternans does not assess arrhythmic risk in patients with Brugada syndrome.

BACKGROUND: Brugada syndrome is associated with a risk for sudden death, but the arrhythmic risk in an individual Brugada syndrome patient is difficult to predict. Pathologic changes in the early repolarization phase of the ventricular action potential probably constitute part of the arrhythmogenic substrate in Brugada syndrome. Microvolt T wave alternans (TWA) assesses dynamic beat-to-beat changes in repolarization and has been suggested as a marker for repolarization-related sudden death. We therefore tested whether TWA is an indicator for arrhythmias in Brugada syndrome with a focus on right precordial ECG leads. METHODS: We assessed TWA in nine symptomatic, inducible patients with established Brugada syndrome and in seven healthy controls. TWA was assessed at rest and during exercise using both standard methods and an algorithm that assesses TWA in the early ST segment and the right precordial leads. RESULTS: None of the Brugada patients developed TWA in this study irrespective of analysis at rest or during exercise, neither using standard methods nor when the early ST segment was included in the analysis. When the early ST segment was included in the analysis, nonsustained TWA was found in three out of seven, and sustained TWA in one control. CONCLUSION: T wave alternans is not an appropriate test to detect arrhythmic risk in patients with Brugada syndrome.

Catheter ablation of ventricular tachycardia by intramyocardial injection of ethanol in an animal model of chronic myocardial infarction.

INTRODUCTION: Direct injection of ethanol into myocardium has been shown to create large, well-demarcated lesions with transmural necrosis in normal ventricular myocardium and in regions of healed myocardial infarction. The aim of this study was to investigate the effects of direct ethanol injection on the inducibility of ventricular tachycardia (VT) in an animal model of chronic myocardial infarction. METHODS AND RESULTS: Eight sheep with reproducibly inducible VT underwent an electrophysiologic study 139 +/- 65 days after myocardial infarction. Noncontact mapping was used to analyze induced VT. Fifteen different VTs were targeted for catheter ablation. Ablation was achieved by catheter-based intramyocardial injection of a mixture of 96% ethanol, glycerine, and iopromide (ratio 3:1:1). Direct intramyocardial ethanol injection resulted in noninducibility of any VT 20 minutes after ablation in 7 of 8 animals. Four of 5 animals with initially successful ablation remained noninducible for any VT at follow-up study at least 2 days after the ablation procedure. Microscopic examination revealed homogeneous lesions with interstitial edema, intramural hemorrhage, and myofibrillar degeneration at the lesion border. The lesions were well demarcated from the surrounding tissue by a border zone of neutrophilic infiltration. CONCLUSION: Catheter ablation of VT by direct intramyocardial injection of ethanol during the chronic phase of myocardial infarction is feasible. It may be a useful tool for catheter ablation when the area of interest is located deep intramyocardially or subepicardially or when a more regional approach requires ablation of larger amounts of tissue.