[Scientific results of the pacemaker register: possibilities and limits]. / Wissenschaftliche Ergebnisse des Herzschrittmacherregisters: Möglichkeiten und Grenzen.

The German obligatory external quality assurance for pacemaker implantation generates a large database giving an almost complete review of in-patient pacemaker interventions since 2001. Publications on lead fixation, age and gender dependency of pacemaker indications, choice of pacing mode and complication rates as well as investigations into the causes of lead dysfunction prove that the database is basically suitable for health service research. In contrast to pacemaker registries of other European countries the focus on in-patient operations, missing product specifications and the absence of patient follow-up largely limits the scientific potential of the database. It is greatly hoped that these limitations will be overcome by cross-sectional and longitudinal quality assurance within the next years.

[Avoidance of ventricular pacing in patients with sinus node disease or intermittent AV block]. / Ventrikuläre Stimulationsvermeidung bei Patienten mit Sinusknotenerkrankung oder intermittierendem AV-Block.

In patients with frequent right ventricular stimulation, worsening of heart failure and atrial fibrillation may occur. Avoidance of unnecessary right ventricular pacing is a major requirement for pacemaker selection and programming in patients with sinus node disease or intermittent AV block. In dual chamber pacemakers this goal can be achieved by programming a long AV delay or an AV delay hysteresis. Algorithms that allow AAI pacing in a dual chamber pacing mode and change to DDD mode in case of high degree AV block are a new attempt to avoid unnecessary right ventricular pacing. The article describes various strategies to avoid unnecessary ventricular pacing and discusses their advantages and disadvantages.

Long term complications in single and dual chamber pacing are influenced by surgical experience and patient morbidity.

OBJECTIVE: To determine how short and long term complication rates after pacemaker implantation are influenced by patient morbidity, operator experience, and choice of pacing system. DESIGN: Retrospective analysis of 1884 patients who received VVI (n = 610), VDD (n = 371), or DDD devices (n = 903) between 1990 and 2001. Follow up period was 64 (34) months. The influence of age, sex, coronary artery disease, myocardial infarction, reduced left ventricular (LV) function, right ventricular (RV) dilatation, atrial fibrillation, device type, and operator experience on operation time and complication rate were analysed. RESULTS: Operation time was prolonged in patients with coronary artery disease, inferior myocardial infarction, reduced LV function, and RV dilatation. Implantation of DDD pacemakers prolonged operation time, particularly among operators with a low or medium level of experience. The overall complication rate was 4.5%. Sixty seven per cent of these complications occurred within the first three months. Complication rate was increased by age, reduced LV function, and RV dilatation. Implantation of DDD systems led to a higher complication rate (6.3%) than implantation of VVI (2.6%) or VDD pacemakers (3.2%). These differences were present only among operators with a low or medium level of experience. CONCLUSIONS: Operation time and complication rate increased with age, impaired LV function, and RV dilatation. Complication rates were higher with DDD than with VVI or VDD implantation and were excessive among inexperienced but not experienced operators.

Red, yellow, green go!--A novel tool for microscopic segregation of secretory vesicle pools according to their age.

Large dense-core vesicles (LDCVs) were labelled in cultured bovine adrenal chromaffin cells expressing fluorescent chimaeric 'cargo' proteins that were targeted to these secretory vesicles. When the cells were stimulated with nicotine 48 h after transduction, the fractional loss of fluorescent LDCVs was much greater than the fractional catecholamine secretion, implying selective release of newly assembled vesicles. This was confirmed using a fluorescent 'timer' construct that changes its fluorescence emission from green to red over several hours, and by measurement of the location and mobility of LDCVs in live cells by confocal fluorescence microscopy. Newly assembled (green) LDCVs were located mostly in peripheral regions of the cells, were virtually immobile and could be released by nicotine, but not by Ba2+; in contrast, older (red) LDCVs were centrally located and relatively mobile, and their exocytotic release was triggered by Ba2+, but not by nicotine. We describe the image restoration procedure that is necessary in order to analyse the behaviour of LDCVs labelled with this construct.

[Preventive pacemaker stimulation in atrial fibrillation]. / Präventive Schrittmacherstimulation bei Vorhofflimmern.

Preventive pacing algorithms and the use of alternative or multifocal pacing sides are new approaches for treatment of paroxysmal atrial tachyarrhythmias. However, present data are not sufficient to define a new indication for pacemaker implantation in patients with refractory atrial fibrillation. Yet, preventive pacing should be predominantly performed either in patients with an established pacemaker indication or during controlled study projects. In patients undergoing cardiac surgery, biatrial overdrive pacing using temporary epicardial wires can be recommended for prevention of postoperative atrial fibrillation.

Over-expression of NCS-1 in AtT-20 cells affects ACTH secretion and storage.

The effect of over-expressing neuronal calcium sensor 1 (NCS-1) upon stimulated adrenocorticotrophin (ACTH) secretion was studied in AtT-20 cells. Stably-transfected AtT-20 cell lines over-expressing NCS-1 were obtained and compared to wild type AtT-20 cells. Corticotrophin releasing factor (CRF-41)-stimulated ACTH secretion from NCS-1 over-expressing cells was significantly reduced from that obtained in wild type AtT-20 cells. The effects of other stimulants of ACTH secretion from wild type AtT-20 cells were not attenuated in NCS-1 over-expressing cells. Calcium, guanosine 5'-O-(3'-thiotriphosphate) (GTP-gamma-S) and mastoparan stimulated ACTH secretion from permeabilised wild type AtT-20 and NCS-1 over-expressing AtT-20 cells with significantly greater ACTH secretion obtained in NCS-1 over-expressing cells. This study shows that in intact cells over-expression of NCS-1 reduces exocytotic ACTH release, while in permeabilised cells increases ACTH release. NCS-1 has multiple cellular targets and that directly and indirectly via these targets acts to increase the releasable ACTH pool while inhibiting CRF-41 stimulus-secretion coupling.

Incidence and predictors of pacemaker dysfunction with unipolar ventricular lead configuration. Can we identify patients who benefit from bipolar electrodes?

Unipolar ventricular leads were implanted in a considerable percentage of pacemaker recipients. There is little information on incidence and risk factors for unipolar pacemaker dysfunction using modern lead designs. Included in a cross-sectional analysis were 682 patients who fulfilled the following criteria: chronically implanted bipolar ventricular leads (> 1 year), intraoperative stimulation threshold < 1.0 V/0.5 ms, and potential amplitude > 6 mV. Incidences of chest wall stimulation (CWS) at an output of twice the amplitude threshold and of myopotential oversensing (MPO) at a sensitivity of half the sensing threshold were assessed. Energy (0.60 [0.72] vs 0.63 [0.81] microJ) and sensing thresholds (8.31 [3.18] mV vs 8.47 [3.47] mV) did not differ between uni- and bipolar modes. While all pacemakers worked properly during bipolar configuration, malfunctions were observed in 5.9% of patients during unipolar configuration (CWS = 1.9%, MPO = 4.2%). Patient age > 76 years (hazard ratio HR 8.2; P < 0.001), heart failure > or = NYHA Class II (HR 3.8; P < 0.001), and an antiarrhythmic therapy with Class I or III drugs (HR 3.3; P = 0.002) were independently associated with the occurrence of unipolar pacemaker dysfunction. Use of steroid-eluting leads reduced the probability of pacemaker dysfunction (HR 0.45; P = 0.03). Risk factors for unipolar ventricular pacemaker malfunction were higher age, heart failure, and antiarrhythmic drug therapy. Particularly in these patients, use of bipolar ventricular leads is beneficial.

Delayed restoration of atrioventricular synchrony with beat-to-beat mode switch.

This case report describes a patient with complete AV block and a VDD pacemaker who experienced repetitive episodes of symptomatic bradycardia. Episodes occurred due to activation of an automatic beat-to-beat mode switch algorithm. After mode switch to VDI operation, the pacemaker failed to immediately switch back to AV synchronous pacing when regular sinus rhythm (> or = 100 beats per minute) resumed despite adequate P wave sensing. Dizziness was felt for up to several minutes of asynchronous pacing at the lower rate limit until VDD mode was restored. Episodes were completely eliminated by programming the mode switch function from an automatic beat-to-beat algorithm to a fixed rate algorithm.

The trigger to cell death determines the efficiency with which dying cells are cleared by neighbours.

Phagocytosis of apoptotic cells is required to prevent tissue injury. Professional phagocytes, such as monocyte-derived macrophages, are highly efficient scavengers of apoptotic cells but their presence cannot always be relied on; in that case, removal of effete cells is accomplished by helpful neighbours. This study describes differences in the efficiency with which apoptotic cells of the same type, but dying in response to different triggers, are engulfed; this varies from engulfment that is so proficient few or no unengulfed apoptotic cells are found, to engulfment that is so delayed apoptotic cells have become secondarily necrotic at the point of engulfment. In all cases the efficiency of engulfment is determined at least in part by the dying cells themselves. p53- and Bax-transfected kidney epithelial (293) cells (transiently transfected using a non-toxic method) were engulfed so proficiently by homotypic neighbours that cells did not show evidence of engagement of the apoptotic programme (chromatin condensation and TUNEL positivity) until engulfment had taken place. Engulfment nonetheless required activation of at least initiator caspases. 293 cells induced to apoptose by other means (etoposide and staurosporine treatment) were not so efficiently ingested: unengulfed apoptotic cells were consistently revealed at all doses and time points, even when treated cells were mixed with healthy, non-treated 293 cells. These data make it extremely unlikely that the fraction of viable, unaffected neighbours determines the efficiency with which engulfment proceeds. Furthermore, 293 cells treated with etoposide or staurosporine were differentially appealing both to homotypic neighbours and to cells in the professional phagocyte lineage (THP-1 cells). If different apoptotic stimuli programme cells to be recognised with different efficiencies, pathways to apoptosis may be injury limiting to greater or lesser degrees.

[Heart rate variability preceding the onset of atrial fibrillation]. / Herzfrequenzvariabilität vor dem Auftreten von Vorhofflimmern.

BACKGROUND: The occurrence of paroxysmal atrial fibrillation is related to changes in autonomic tone. Vagally mediated atrial fibrillation predominantly occurs at night in young male patients without history of structural heart disease. In contrast, sympathetically mediated atrial fibrillation is typically triggered by stress. ANALYSIS OF HEART RATE VARIABILITY: Heart rate variability usually measured by Holter monitoring can determine changes in autonomic tone immediately preceding the onset of atrial fibrillation. Studies on this topic found divergent results on the incidence of atrial fibrillation mediated by changes in autonomic tone. Dependent on the results of different studies, night-time episodes of idiopathic atrial fibrillation either are vagally or sympathetically mediated. A sympathetic predominance is found in patients after coronary bypass surgery, concordantly. The inconsistency of these findings points to the fact that not only one mechanism, but more complex changes in autonomic tone are responsible for the occurrence of atrial fibrillation in many cases. In modern pacemakers and implantable cardioverter-defibrillators, PP or RR intervals can be stored automatically before the onset of an arrhythmia. By use of these stored intervals, time-domain parameters of heart rate variability can be calculated. We determined changes in short-term heart rate variability (10-second intervals) by analyzing 26 episodes of PP intervals sampled over the last 2 minutes before onset of atrial fibrillation by a modern dual chamber pacemaker. We observed a significant increase of the standard deviation of PP intervals (SDNN10s) as well as of the mean square route of the squared PP intervals (rMSSD10s) within the last 10-second interval before onset of atrial fibrillation (p < 0.05). This finding points to changes in autonomic tone-immediately preceding the onset of atrial fibrillation. CONCLUSION: The preliminarity of these findings and the use of yet not validated short intervals for determination of heart rate variability does not allow to draw pathogenetic or even therapeutic conclusions from these findings.

Cost-effectiveness of dual-chamber pacemaker therapy: does single lead VDD pacing reduce treatment costs of atrioventricular block?

AIMS: Implantation of single-lead VDD pacemakers is an established alternative to DDD pacing in patients with atrioventricular block. This study compares the long-term costs of both systems. METHODS AND RESULTS: Three hundred and sixty patients with atrioventricular block received VDD or DDD pacemakers in alternating order. Primary costs of implantation included: devices, leads and operation material, surgeons, nurses, medical technicians, and hospitalization. The mean cost of an uncomplicated DDD pacemaker implantation was defined as 1000 virtual cost-units (CU). Costs of pacemaker related complications or re-operations as well as upgrades from VDD to DDD devices were considered secondary costs and assessed during a mean follow-up period of 42+/-15 months. Pacing efficacy was assessed by event-free survival with maintained atrioventricular synchronized pacing mode. Costs of pacemaker devices were not different (639+/-26 CU in VDD vs 641+/-32 CU in DDD, ns). However, due to lower costs of lead hardware (102+/-10 CU in VDD vs 133+/-14 CU in DDD, P<0.001) and shorter implantation procedures (44.3+/-5.1 min vs 74.4+/-13.5 min, P<0.001), costs of an uncomplicated implantation were 8.9% lower in the VDD group (911+/-35 CU vs 1000+/-39 CU, P<0.001). A smaller complication rate in the VDD group led to a 16.1% reduction of secondary costs (26+/-17 CU year(-1)vs 31+/- 25 CU year(-1), P=0.024). Event-free survival did not differ between groups (83.4% in VDD vs 84.9% in DDD, ns). CONCLUSION: Use of single-lead VDD pacemakers achieves significant reduction of implantation and follow-up costs without loss of therapeutic efficacy compared to conventional DDD systems.

Course and prognostic implications of QT interval and QT interval variability after primary coronary angioplasty in acute myocardial infarction.

OBJECTIVES: The aim of this study was to determine the influence of early reperfusion on the course of QT interval and QT interval variability in patients undergoing primary percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction (AMI) and its prognostic implications on major arrhythmic events during one-year follow-up. BACKGROUND: Although early coronary artery recanalization by primary angioplasty is an established therapy in AMI, a substantial number of patients is still threatened by malignant arrhythmias even after early successful reperfusion, which may be caused by an inhomogeneity of ventricular repolarization despite reperfusion. METHOD: Temporal fluctuations of ventricular repolarization were studied prospectively in 97 consecutive patients with a first AMI by measurements of QT interval and QT interval variability during and after successful PTCA (Thrombolysis in Myocardial Infarction flow grades 2 and 3). Continuous beat-to-beat QT interval measurement was performed from 24-h Holter monitoring, which was initiated at admission before PTCA. RESULTS: Reperfusion caused a significant continuous increase of mean RR interval (738 +/- 98 to 808.5 +/- 121 ms; p < 0.001) and a significant decrease of parameters of QT interval (QTc: 440 +/- 32 to 416.5 +/- 37ms; p < 0.001) and QT interval variability (QTcSD: 27.5 +/- 3 to 24.9 +/- 6 ms; p < 0.001) in the majority of patients. However, in patients with major arrhythmic events at the one-year follow-up (sudden cardiac death, ventricular fibrillation or sustained ventricular tachycardia, n = 15), parameters of QT interval remained unaltered after successful reperfusion (QTc: 447.3 +/- 41 to 432.9 +/- 45 ms, p = NS; QTcSD: 35.1 +/- 13.4 to 29.0 +/- 9.1 ms, p = NS). CONCLUSIONS: Reduction of QT interval and QT interval variability after timely reperfusion of the infarct-related artery may be a previously unreported beneficial mechanism of primary PTCA in AMI, indicating successful reperfusion.

Effectiveness of end-tidal carbon dioxide tension for monitoring thrombolytic therapy in acute pulmonary embolism.

OBJECTIVE: In acute massive pulmonary embolism with hemodynamic instability, monitoring of pulmonary artery pressure can be used to assess the efficacy of thrombolytic therapy. As a noninvasive alternative to pulmonary artery catheterization, we investigated the efficacy of continuous monitoring of end-tidal CO2 tension. DESIGN: In 12 patients with massive pulmonary embolism who required mechanical ventilation, mean pulmonary arterial pressure (MPAP) and end-tidal carbon dioxide tension (ETCO2) were registered continuously during thrombolytic therapy. PaCO2, cardiac index as estimated by thermodilution catheter and respiratory ratio of arterial oxygen tension and inhaled oxygen concentration (PaO2/FIO2) were determined every 60 mins. MEASUREMENTS AND MAIN RESULTS: Before thrombolysis, MPAP (34.5+/-9.8 mm Hg) and the difference between PaCO2 and ETCO2 (10.1+/-4.7 mm Hg) were markedly increased compared with normal values. Continuously monitored MPAP was related to ETCO2 for both all patients (r2 = .42; p < .001) and individually (mean r2 = .92; range, .79-.98; p < .001). In ten survivors, the mean cardiac index and PaO2/FIO2 increased during therapy from 1.7+/-0.4 to 2.8+/-0.6 L/min x m2 and 125+/-27 to 285+/-50 mm Hg (p < .01, respectively). In these patients, the difference between PaCO2 and ETCO2 decreased from 9.8+/-4.5 to 2.8+/-0.9 mm Hg (p < .001). Recurrent embolism was detected in two patients by sudden reduction of ETCO2. CONCLUSIONS: Analysis of ETCO2 allows monitoring of the efficacy of thrombolysis and may reflect recurrent embolism. Thus, on the basis of this small study, analysis of ETCO2 appears to be useful for noninvasive monitoring in mechanically ventilated patients with massive pulmonary embolism.

Risk stratification in patients with inferior acute myocardial infarction treated by percutaneous coronary interventions: the role of admission troponin T.

BACKGROUND: Cardiac troponin T (cTnT) elevations on admission indicate a high-risk subgroup of patients with ST-segment elevation acute myocardial infarction (AMI). This finding has been attributed to less effective reperfusion after thrombolytic therapy. The aim of this study was to determine the role of admission cTnT on the efficacy of percutaneous coronary interventions (PCIs) in inferior AMI. METHODS AND RESULTS: One hundred fifty-nine consecutive patients with inferior ST-segment AMI were enrolled and followed up for a mean of 448 days. Patients were stratified by cTnT on admission. A cTnT >/=0.1 microg/L was found in 58% of patients. These patients had longer time intervals from onset of symptoms to therapy (P:<0. 001) and higher 30-day (10.8% versus 1.5%, P:=0.027) and long-term (17.2% versus 4.5%, P:=0.023) cardiac mortalities. Rates of the combined end point of death, nonfatal reinfarction, and need for repeated target vessel revascularization procedures were not different in cTnT groups (log rank, 0.69; P:=0.41). PCI was attempted in 93.3% of cTnT-positive and 98.5% cTnT-negative patients (P:=0.24) but was less frequently successful in patients with cTnT >/=0.1 microg/L (77.9% versus 96.9%, P:<0.001). Coronary stenting reduced 30-day and long-term cardiac mortality, particularly among cTnT-positive patients. In a multivariate analysis, cTnT indicated an approximately 5-fold-higher risk (adjusted OR, 4.6; 95% CI, 0.79 to 27.11; P:=0.089) and was a strong albeit not independent risk predictor. CONCLUSIONS: In inferior AMI, a positive admission cTnT is associated with lower success rates of direct PCI and higher rates of cardiac events over the short and long term. These patients benefit from coronary stenting.

Long-term superiority of steroid elution in atrial active fixation platinum leads.

Steroid elution reduces the acute increase in stimulation threshold particularly in active fixation leads. The aim of this study was to investigate the long-term efficacy of steroid elution in atrial screw-in leads compared to conventional lead design. Two different bipolar active fixation platinum lead designs were implanted. Leads were similar except for the presence (group S, n = 66) or absence (group N, n = 68) of steroid elution. Patients received dual chamber pacemakers with the following atrial leads in consecutive order: Medtronic 4058 M (group N, n = 30), Medtronic 4068 (group S, n = 40), Vitatron IMS 13 (identical to 4058 M, group N, n = 38), and Vitatron IMX 13 (identical to 4068, group S, n = 26). The mean follow-up period was 40.7 +/- 16.1 months (range 10 to 84 months). Stimulation thresholds, pacing impedances, P wave potentials, and sensing threshold were assessed for both groups immediately, 10 days, 6 weeks, and 3 months after implantation followed by 6-months intervals. Energy thresholds, chronaxie-rheobase products, and energy consumption of atrial pacing were calculated. Chronic values were deduced from the most recent measurement performed in an individual patient. Within the first 10 days after implantation, atrial voltage threshold at pulse duration of 0.4 ms increased from 0.91 +/- 0.42 to 2.06 +/- 0.45 V in group N (P < 0.001). Less increase was observed in group S (0.83 +/- 0.39 to 1.08 +/- 0.53 V, P = 0.003). Atrial voltage thresholds remained markedly lower in steroid-eluting leads during whole follow-up (1.12 +/- 0.49 V in group S vs 1.58 +/- 0.71 V in group N, P < 0.001). Chronic energy consumption was markedly reduced in group S (4.0 +/- 2.7 microJ) compared to group N (9.8 +/- 7.5 microJ, P < 0.001). An atrial voltage threshold below 1.25 V at 0.4 ms was achieved in 92.3% of patients of group S allowing programming of an output of 2.5 V. Such low outputs were feasible in only 49.3% of patients in group N (P < 0.001). Chronic P wave amplitudes did not differ significantly between groups (3.27 +/- 1.81 mV in group N vs 3.24 +/- 1.18 mV in group S, P = 0.91). Steroid elution diminishes the increase of stimulation thresholds of nonsteroid atrial active fixation platinum leads resulting in a long-term reduction of energy consumption. Thus, use of steroids can be recommended for general use in atrial active fixation lead designs.