No abstract

Initial experience with the Medtronic Jewel 7250, the ICD designed to detect and treat ventricular and supraventricular tachyarrhythmias, is very promising. Its effectiveness, however, depends on sensing performance, which has not yet been systematically examined. The aim of the study was to determine the incidence of, predisposing factors for, and practical implications of far-field R wave oversensing (FFRWOS) in this dual chamber ICD. During a total follow-up of 797 months in 48 patients who had the Jewel 7250, follow-up strip charts, 12-channel Holter recordings and, in particular cases, Holter recordings with intracardiac markers were analyzed for the presence of FFRWOS. FFRWOS was documented in ten (21.3%) patients. Compared to other lead locations, the right atrial appendage lead position was most frequently associated with FFRWOS (7/27 vs 3/21, P < 0.05). Patients with FFRWOS had significantly more treated and nontreated atrial episodes, many of which were judged to have been detected inappropriately. In one case, inappropriate atrial antitachycardia pacing due to R wave oversensing triggered sustained ventricular tachycardia, terminated eventually with a high energy shock. In dual chamber ICDs, FFRWOS may represent a frequent phenomenon possibly leading to serious consequences. For atrial leads, a lateral atrial wall position seems to be preferable. In most cases, FFRWOS can be eliminated by optimization of atrial sensing parameters. Given the possibility of ventricular proarrhythmia with atrial pacing therapy, the capability of ventricular backup defibrillation in respective devices is at least reassuring.

Patient-alert features are a useful additional tool facilitating early detection of serious ICD complications, but they do not substitute for regular ICD follow-up, because of their low sensitivity.

Budipine is a non-dopaminergic antiparkinsonian drug causing acquired forms of Long QT syndrome (aLQTS). As a consequence, the manufacturer has restricted the use of budipine in patients who exhibit additional risk factors for the development of "Torsades-de-Pointes" tachycardias (TdP). The molecular basis of this serious side effect has not been elucidated yet. Human ether-a-go-go related gene (HERG) channel block being the main cause of drug induced QT prolongation, we investigated the effect of budipine on the rapid component of the delayed-rectifier potassium current (I(K(r))) in guinea pig cardiomyocytes and on HERG potassium channels heterologously expressed in Xenopus oocytes. In guinea pig cardiomyocytes, budipine (10 microM) inhibited I(K(r)) by 86% but was without any effect on calcium currents. In Xenopus oocytes, HERG potassium channels were blocked by budipine with an IC(50) of 10.2 microM. Onset of block was fast and block was only slowly and incompletely reversible upon washout. Budipine blocked HERG channels in the open and inactivated state, but not in the closed states. The half-maximal activation voltage was slightly shifted towards more negative potentials. Steady-state inactivation of HERG was also influenced by budipine. Budipine block was neither voltage- nor frequency-dependent. In HERG channel mutants Y652A and F656A, drug affinity was reduced dramatically. Therefore, these two aromatic residues in the channel pore are likely to form a main part of the binding site for budipine. In summary, this is the first study that provides a molecular basis for the budipine-associated aLQTS observed in clinical practice. Furthermore, these findings underline the importance of the aromatic residues Y652 and F656 in the binding of lipophilic drugs to HERG channels.

Sustained short-term ethanol infusion in rabbits alters atrial current densities. HHS might be favored by alcohol-induced atrial electrical remodeling.

This pilot study demonstrates that HM enables early detection of ICD failure and appears to enhance patient safety.

In the MADIT study, a selected group of postinfarction patients with asymptomatic nonsustained ventricular tachycardia (NSVT) has been shown to benefit from prophylactic ICD treatment. The present study analyzed the variability of NSVT in a patient population fulfilling the non-invasive MADIT criteria. Three consecutive Holter ECGs were performed in weekly intervals in 68 postinfarction patients with an LVEF < or = 0.35. Patients with NSVT underwent programmed ventricular stimulation (PVS); patients were implanted with an ICD if sustained VT or VF was inducible. If NSVT was found in at least two recordings, the arrhythmia was defined as reproducible. In 28 (41%) of the 68 patients, NSVT was found in at least one recording. Seventeen patients revealed NSVT in the first, the remaining 11 in the second registration; no patient had NSVT only in the third Holter. Of the patients with NSVT, 50% had only one, 39% had two, and 11% had three positive recordings. Thus, reproducible NSVT was found in only 50% of the patients with NSVT. Predictors for reproducibility were LVEF > 0.27, NYHA Class I, absence of digitalis therapy, and > 2 NSVT per 24-hour period. Reproducible NSVT was not associated with risk factors such as elevated mean heart rate, reduced heart rate variability, late potentials, or inducibility of sustained VT during PVS. During 17 +/- 9 months of follow-up, seven (10%) patients experienced arrhythmic events: two without and five with previously documented NSVT. In the latter patients, first occurrence of NSVT was consistently in the first Holter; only two of them had reproducible NSVT. In postinfarction patients, the risk factor NSVT exhibits marked spontaneous variability, especially in those with a low number of NSVT per 24-hour period, LVEF < 0.27 or NYHA III, which limits its clinical value as a selection criterion for PVS. Reproducibility of NSVT itself does not seem to be an independent risk factor.

Summary.  Aims: Blood cell infiltration and inflammation are involved in atrial remodelling during atrial fibrillation (AF) although the exact mechanisms of inflammatory cell recruitment remain poorly understood. Platelet‐bound stromal cell‐derived factor‐1 (SDF‐1) is increased in cases of ischemic myocardium and regulates recruitment of CXCR4+ cells on the vascular wall. Whether platelet‐bound SDF‐1 expression is differentially influenced by non‐valvular paroxysmal or permanent atrial fibrillation (AF) in patients with stable angina pectoris (SAP) or acute coronary syndrome (ACS) has not been reported so far. Methods and results: A total of 1291 consecutive patients with coronary artery disease (CAD) undergoing coronary angiography were recruited. Among the patients with SAP, platelet‐bound‐SDF‐1 is increased in patients with paroxysmal AF compared with SR or to persistent/permanent AF (P < 0.05 for both). Platelet‐bound SDF‐1 correlated with plasma SDF‐1 (r = 0.488, P = 0.013) in patients with AF and ACS, which was more pronounced among patients with persistent AF (r = 0.842, P = 0.009). Plasma SDF‐1 was increased in persistent/permanent AF compared with SR. Patients with ACS presented with enhanced platelet‐bound‐SDF‐1 compared with SAP. Interestingly, among patients with ACS, patients with paroxysmal or persistent/permanent AF presented with an impaired platelet‐bound SDF‐1 expression compared with patients with SR. Conclusions: Differential expression of platelet‐bound and plasma SDF‐1 was observed in patients with AF compared with SR which may be involved in progenitor cell mobilization and inflammatory cell recruitment in patients with AF and ischemic heart disease. Further in vivo studies are required to elucidate the role of SDF‐1 in atrial remodeling and the atrial fibrillation course.