[Deterministic record linkage with indirect identifiers: data of the Berlin Myocardial Infarction Registry and the AOK Nordost for patients with myocardial infarction]. / Deterministisches Record Linkage mit indirekten Identifikatoren: Daten des Berliner Herzinfarktregisters und der AOK Nordost zum Herzinfarkt.

AIM OF THE STUDY: How can 2 pseudonymised data sets be linked? Using the example of data from the Berlin Myocardial Infarction Registry and from a German sickness fund (AOK Nordost) we will demonstrate how record linkage can be achieved without personal identifiers. METHODS: In different steps the method of deterministic record linkage with indirect identifiers: age, sex, hospital admission date and time, will be explained. RESULTS: We were able to show that 80.6% of the expected maximum number of patients were matched with our approach. As a result we had no duplicate matches in the linkage process, where one AOK patient was linked to 2 or more BMIR patients or vice versa. The matching variables produced enough uniqueness to be used as indirect patient identifiers. CONCLUSION: Deterministic record linkage with the following indirect indicators: age, sex, hospital admission date and time was possible in our study of patients with myocardial infarction in a circumscribed geographical region, which limited the number of cases and avoided mismatches.

[Treatment of ST-segment elevation acute myocardial infarction in hospitals with and without cardiac catheterization laboratory]. / Therapie des akuten ST-Streckenhebungs-Myokardinfarkts in Krankenhäusern mit und ohne Herzkatheterlabor.

BACKGROUND AND OBJECTIVE: The goal of treatment of patients with ST-segment elevation acute myocardial infarction (STEMI) is to restore perfusion as soon as possible, preferably by primary percutaneous coronary intervention (PCI). The aim of this study of the German Myocardial Infarction Registry (DHR) was to document acute care and in-hospital course of STEMI patients in Germany. METHODS: Over three months patients with STEMI were consecutively included and their basic data, treatments and in-hospital complications were centrally recorded using an internet-based standardized questionnaire. RESULTS: Included were 6,330 patients from 243 hospitals, in group 1 (primary admission in 136 hospitals with cath lab) 4,656 patients (74%) and in group 2 (primary admission in 107 hospitals without cath lab) 1,674 (26%). Reperfusion therapy was performed more frequently in patients of group 1 (91.1% PCI, 2.7% fibrinolysis) than in group 2 (80.7% PCI after transfer, 6.4% fibrinolysis). In-hospital mortality was 7.3% in all patients, 7.0% in group 1 and 8.3% in group 2. CONCLUSION: The DHR data show that about three quarters of patients with STEMI are primarily admitted to hospitals with cath labs. Primary PCI is the preferred treatment option both in hospitals with and without cath labs (in the latter after transfer); it is performed in about 85% of STEMI patients. In-hospital mortality is with over 7% higher in real-life than in randomized studies.

Predictors of chronotropic incompetence in the pacemaker patient population.

AIMS: We prospectively evaluated results from cardiopulmonary exercise testing for chronotropic incompetence (CI) in a cohort of 292 pacemaker patients. In addition, we evaluated comorbidity and antiarrhythmic patient data as indicators of CI. METHODS AND RESULTS: On the basis of exercise stress testing and application of the definition of CI by Wilkoff, 51% of our cohort was categorized as having CI. Indications for pacemaker implant for this patient group were 42% atrioventricular block, 56% sinus node disease, and 59% atrial fibrillation. Maximum oxygen uptake (VO(2) max) and exercise duration were significantly reduced among CI pacemaker patients, whereas oxygen uptake at the anaerobic threshold remained unchanged. The following clinical characteristics were significant predictors of CI: existence of coronary artery disease (P = 0.038), presence of an acquired valvular heart disease (P = 0.037), and former cardiac surgery (P = 0.041). Age, gender, arterial hypertension, cardiomyopathy, congenital heart disease, left ventricular ejection fraction, and time period between stress-exercise examination and pacemaker implantation were not significant predictors of CI. Chronic antiarrhythmic therapy with digitalis (P = 0.013), beta blockers (P = 0.036), and amiodarone (P = 0.045) were significant predictors of CI. In contrast, medication with class I and IV antiarrhythmics had no significant correlation with CI. CONCLUSION: We found the following characteristics predictive of CI in this pacemaker patient population: VO(2) max, existence of coronary artery disease or acquired valvular heart disease, previous cardiac surgery, as well as medication with digitalis, beta blockers, and amiodarone.

Hospital care of patients with ST-elevation myocardial infarction in four different European regions. Data from four regional myocardial infarction registries in Berlin, Dijon, Florence, and Tartu.

National surveys as well as European comparative studies suggest that differences in treatment of patients with ST-elevation myocardial infarction (STEMI) exist. The extent to which these variations influence the outcome of hospital care delivered to STE-MI patients in everyday routine is mostly unknown. In this study data representative of hospital care received by STEMI patients in four European regions (Berlin, Dijon, Florence and Tartu) were compared. The four registries are population based. The percentage of women and the mean age of the patients differed among the registries. Risk factors such as hypertension and hypercholesterolaemia also differed among the different regions, whereas a history of diabetes mellitus was similar among the registries. The percentage of patients receiving reperfusion therapy ranged from 47 to 81%. An appreciable difference also resulted after breaking down reperfusion therapy into thrombolysis and primary percutaneous coronary intervention (PCI). Hospital mortality as an outcome measure was very similar among the regions. After adjustment for age, the comparative magnitude of hospital mortality proportion was also very similar among three registries. Only the patients from Florence demonstrated a comparatively lower death rate, with a ratio of 0.81. In summary, there are important differences among baseline characteristics and hospital care of STE-Ml patients in the four study regions. Nevertheless, it was interesting to ascertain that the outcome measured in hospital mortality was very similar among the four registries compared.

Influence of gender on treatment and short-term mortality of patients with acute myocardial infarction in Berlin.

AIMS: Previous studies have shown higher hospital mortality rates in women, especially younger women, than in men. In light of the fact that myocardial infarction therapy is rapidly developing, and since gender-specific aspects have been discussed in detail during recent years, it was our goal to re-evaluate factors influencing hospital mortality rate, especially those involving gender-specific differences, in the city of Berlin, Germany. METHODS: We prospectively collected data from 5133 patients (3330 men and 1803 women) with acute myocardial infarction who were treated in 25 hospitals in Berlin during the years 1999 to 2002. RESULTS: During hospitalization the overall mortality rate was 18.6% among women and 8.4% among men. Women were older (mean age for men 62 years; women 73 years) and less likely to be married (men 74.6%; women 36.9%) than men. Women generally took longer to arrive at the hospital after infarction than did men (median time: men 2.0 h; women 2.6 h). Women furthermore demonstrated a higher proportion of diabetes (men 22.8%; women 36.5%) and hypertension (men 58.0%; women 69.3%). Reperfusion therapy (men 68.8%; women 49.7%) and administration of beta-blockers (men 76.0%; women 66.0%) took place less often for women than for men. A multivariate analysis revealed the following factors to be independent predictors of hospital mortality: age, gender, diabetes mellitus, hypercholesterolemia, pre-existing heart failure, pre-hospital cardiopulmonary resuscitation, cardiogenic shock and pulmonary congestion on admission, admission to a hospital with >600 beds, ST-elevation in the initial ECG, reperfusion therapy, as well as beta-blocker and ACE inhibitor treatment within 48 h of hospitalization. CONCLUSION: Even after adjustment in multivariate analysis, women with acute myocardial infarction still demonstrate a higher risk for in-hospital death than men.

Echocardiographic AV-interval optimization in patients with reduced left ventricular function.

BACKGROUND: Ritter's method is a tool used to optimize AV delay in DDD pacemaker patients with normal left ventricular function only. The goal of our study was to evaluate Ritter's method in AV delay-interval optimization in patients with reduced left ventricular function. METHODS: Patients with implanted DDD pacemakers and AVB III degrees were assigned to one of two groups according to ejection fraction (EF): Group 1 (EF > 35%) and Group 2 (EF < 35%). AV delay optimization was performed by means of radionuclide ventriculography (RNV) and application of Ritter's method. RESULTS: For each of the patients examined, we succeeded in defining an optimal AV interval by means of both RNV and Ritter's method. The optimal AV delay determined by RNV correlated well with the delay found by Ritter's method, especially among those patients with reduced EF. The intra-class correlation coefficient was 0.8965 in Group 1 and 0.9228 in Group 2. The optimal AV interval in Group 1 was 190 +/- 28.5 ms, and 180 +/- 35 ms in Group 2. CONCLUSION: Ritter's method is also effective for optimization of AV intervals among patients with reduced left ventricular function (EF < 35%). The results obtained by RNV correlate well with those from Ritter's method. Individual programming of the AV interval is fundamentally essential in all cases.

Mechanically induced potentials in rat atrial fibroblasts depend on actin and tubulin polymerisation.

When atrial tissue contracts, mechanically induced potentials (MIPs) are generated in fibroblasts, presumably by activation of a non-selective cation conductance Gns. Non-stimulated atrial fibroblasts had a mean (+/-SD) membrane potential (Em) of -22 +/- 2 mV and an input resistance of 510 +/- 10 MS. MIP amplitude (AMIP) was 38+/-4 mV when current injection had polarised Em to Vm = -50 mV. The slope of the function relating AMIP to Vm can be regarded as a mechanosensitive factor (Xms) that describes the relative increase in Gns during a MIP. Putative involvement of cytoskeletal fibres in activation of Gns was studied by delivering drugs from the intracellular recording microelectrode. Destabilisation of F-actin by 0.2 mM cytochalasin D reduced AMIP from 38 to 16 mV and Xms from 5 to 1.8. Destabilisation of tubulin with 0.2 mM colchicine reduced AMIP to 21 mV and Xms to 2.1. The combination colchicine plus cytochalasin D reduced AMIP to 9 mV and Xms to 1.4. Promoting F-actin stability with exogenous adenosine 5'-triphosphate (ATP) increased AMIP and Xms and attenuated the effects of cytochalasin D. Similarly, facilitation of tubulin stability with guanosine 5'-triphosphate (GTP) or taxol increased AMIP and Xms and attenuated the effects of colchicine. The results suggest that transfer of mechanical energy from the deformed fibroblast surface to the Gns channel protein depends on intact F-actin and tubulin fibres.

Transient exit block of a DDD pacemaker with unipolar leads in subcutaneous emphysema following pneumothorax.

This case report describes a transient pacemaker exit block due to subcutaneous emphysema following pneumothorax. Pneumothorax after pacemaker implantation is rare, but development of subcutaneous emphysema under such circumstances is even more uncommon. Exit block develops only with the use of unipolar leads; with implantation of bipolar leads, this complication cannot occur.

R-wave detection by subcutaneous ECG. Possible use for analyzing R-R variability.

BACKGROUND: Atrial arrhythmia (AA) discrimination remains a technological challenge for implanted cardiac devices. We examined the feasibility of R-wave detection by a subcutaneous far field ECG (SFFECG) and analysis of these signals for R to R variability as an indicator of atrial arrhythmia (AA). METHODS: Surface ECG and SFFECG (from the pacemaker pocket) were recorded in sixteen patients (61.5 +/- 11.4 years) with AA. The SFFECG was recorded with a pacemaker sized four electrode array acutely placed in the pacemaker pocket during implantation. The signals were analyzed to obtain peak-to-peak R wave amplitude and R to R interval variability (indicative of AAs). RESULTS: In sixteen patients R waves were visually discernible in all recordings. The percentage over and under detection for automatic R wave recognition SFFECG was 3 and 9%, respectively. R to R variability analysis using the SFFECG produced results concordant to those using the surface ECG. CONCLUSION: SFFECG might be a helpful adjunct in implantable device systems for detection of R waves and may be used for measurement of R to R variability.

Functional similarity between electrograms recorded from an implantable cardioverter defibrillator emulator and the surface electrocardiogram.

Clinical use of stored electrogram (EGM) configurations currently used in ICDs is limited. The hypothesis that EGMs recorded from electrodes on the ICD surface may improve diagnostic capabilities of the device was tested in the present study. The Buttons on Active Can Emulator (BACE), an ICD-sized device containing four button electrodes, was temporarily placed into a subcutaneous or submuscular left pectoral pocket in 16 patients during ICD implantation. Simultaneous recordings were obtained from the ECG lead II, bipolar EGMs using BACE electrodes, and a bipolar atrial EGM during sinus rhythm (SR), ventricular pacing (VP) at cycle lengths of 500 and 400 ms, and VT. Visible P waves were present in all patients during SR (n = 15), in 5 (33%) of 15 patients during VP, and none of the patients during VT (n = 4) using BACE EGMs and lead II. P and QRS amplitudes and the P:QRS ratio during SR in BACE EGMs were significantly lower than those in lead II. BACE EGMs showed prominent changes in QRS morphology and duration during VP and VT compared to SR, and the magnitude of QRS prolongation during VP was similar to that in lead II. Measurements of PR, QRS, and QT duration during SR showed good agreement between BACE EGMs and lead II. In conclusion, EGMs recorded from electrodes embedded on the ICD housing may potentially improve visual discrimination between supraventricular and ventricular arrhythmias. They also may be useful as a surrogate of the ECG for analysis and monitoring of different components of P-QRS-T complex.

Contractile function of rat myocardium is less susceptible to hypoxia/reoxygenation after acute infarction.

In this study we tested the hypothesis that induction of heat shock proteins (HSPs) and antioxidant enzymes is a compensatory mechanism, which preserves the contractility of the surviving myocardium after acute myocardial infarction. For this purpose, mechanical function of isolated rat papillary muscles was tested 15 h after experimental myocardial infarction and sham operation, respectively. Contractility of the preparations was compared to the expression of HSP25, HSP72, and glutathione peroxidase activity (GSH-Px) at normoxia and during hypoxia/reoxygenation. At normoxic conditions, rates of isometric contraction and, in particular, of relaxation were significantly higher after acute myocardial infarction than after sham operation. Improved relaxation rates were reflected in 2- to 3-fold higher heat shock protein levels in papillary muscles from rats with myocardial infarction compared to sham operated animals. During hypoxia/reoxygenation, the rates of contraction and relaxation were better preserved after myocardial infarction than after sham surgery. Recovery of relaxation rates during reoxygenation was associated with increased HSP25 levels and enhanced GSH-Px activity after myocardial infarction. In conclusion, heat shock proteins exert a beneficial effect on cardiac muscle relaxation after acute myocardial infarction. Enhanced heat shock protein expression and GSH-Px activity may protect the contractile function of the surviving myocardium against the damaging influence of hypoxia/reoxygenation during the early post-infarct period.

Myocardial contractility after infarction and carnitine palmitoyltransferase I inhibition in rats.

Inhibition of carnitine palmitoyltransferase I with etomoxir increases sarcoplasmic reticulum Ca(2+)-transport and V(1) isomyosin expression. To test whether etomoxir attenuates contractile dysfunction after myocardial infarction, we compared the contractility of papillary muscles from etomoxir- and placebo-treated rats 6 weeks after infarction. Etomoxir induced cardiac hypertrophy in animals with small infarctions, and enhanced compensatory heart growth at large infarct size. Contractile function of papillary muscles from etomoxir-treated rats was improved particularly in animals with small infarctions. Thus, induction of mild cardiac hypertrophy by etomoxir in rats with small infarctions may be beneficial for myocardial performance.

Blunted arterial baroreflex causes "pathological" heart rate turbulence.

Sudden cardiac death is the leading cause of cardiovascular mortality in developed countries. Recently, two post-myocardial-infarction risk predictors were introduced that are superior to all other presently available indicators: turbulence onset (TO) and turbulence slope (TS). These parameters characterize the behavior of instantaneous heart rate after a ventricular premature beat, i.e., they describe the reestablishing of heart rate control after an acute perturbation. We propose that the dysfunction of an important cardiovascular control mechanism, the arterial baroreflex, is the mechanism behind these new potent markers. The hypothesis is tested by means of a physiological model involving the excitation generation in the heart, the hemodynamic situation in the aorta, and baroreceptor feedback mechanisms. The data show that a blunted baroreceptor response of the heart resembles patterns of heart rate turbulence that correspond to pathological values of TO and TS. The results of the model suggest that the recently established risk parameters TO and TS characterize baroreflex function, a known risk stratifier in patients.

A1166C polymorphism of the angiotensin II type 1 receptor gene and risk of adverse events after coronary catheter interventions.

BACKGROUND: Contradictory reports exist concerning the role of the angiotensin II type 1 receptor A1166C polymorphism as a coronary risk factor. Moreover, it is unknown whether the A1166C polymorphism is associated with thrombotic complications after coronary catheter interventions. METHODS: We investigated the role of the A1166C polymorphism as a risk factor in 1000 patients with coronary artery disease (CAD) and in 1000 age- and sex-matched controls. A total of 649 patients receiving interventions (270 coronary angioplasty, 102 atherectomy, and 277 stenting) were investigated for a 30-day composite end point including target vessel revascularization, myocardial infarction, or death. RESULTS: The composite end point was reached by 42 patients (6.5%) without evidence that the C allele was associated with excess procedural risk (odds ratio 0.93; 95% confidence interval 0.79-1.75; P =.82). Further analyses by device failed to show linkage with adverse events complicating coronary angioplasty, atherectomy, and stenting. Moreover, in the entire CAD group (n = 1000), the polymorphism even showed a trend to underrepresentation (odds ratio 0.83; 95% confidence interval 0.69-1. 004, P =.054). CONCLUSIONS: These results indicate that the A1166C polymorphism neither represents a risk factor for adverse events complicating coronary interventions nor seems to have significant impact on further long-term processes such as development and severity of CAD.

P wave and far-field R wave detection in pacemaker patient atrial electrograms.

This study was undertaken to develop and test a morphology-based adaptive algorithm for real-time detection of P waves and far-field R waves (FFRWs) in pacemaker patient atrial electrograms. Cardiac event discrimination in right atrial electrograms has been a problem resulting in improper atrial sensing in implantable devices; potentially requiring clinical evaluation and device reprogramming. A morphology-based adaptive algorithm was first evaluated with electrograms recorded from 25 dual chamber pacemaker implant patients. A digital signal processing (DSP) system was designed to implement the algorithm and test real-time detection. In the second phase, the DSP implementation was evaluated in 13 patients. Atrial and ventricular electrograms were processed in real-time following algorithm training performed in the first few seconds for each patient. Electrograms were later manually annotated for comparative analysis. The sensitivity for FFRW detection in the atrial electrogram during off-line analysis was 92.5% (+/- 10.9) and the positive predictive value was 99.1% (+/- 1.8). Real-time P wave detection using a DSP system had a sensitivity of 98.9% (+/- 1.3) and a positive predictivity of 97.3% (+/- 3.5). FFRW detection had a sensitivity of 91.0% (+/- 12.4) and a positive predictivity of 97.1% (+/- 4.2) in atrial electrograms. DSP algorithm tested can accurately detect both P waves and FFRWs in right atrium real-time. Advanced signal processing techniques can be applied to arrhythmia detection and may eventually improve detection, reduce clinician interventions, and improve unipolar and bipolar lead sensing.

Oxygen radical system in chronic infarcted rat heart: the effect of combined beta blockade and ACE inhibition.

In vitro experiments suggest that beta blockade and angiotensin-converting enzyme (ACE) inhibition may protect the failing heart by reduction of myocardial oxidative stress. To test this hypothesis in an in vivo model, the beta blocker metoprolol (350 mg) and the ACE inhibitor ramipril (1 mg) were given either alone or in combination to rats (per kilogram body weight per day) for 6 weeks after myocardial infarction. Left ventricular end-diastolic pressure (LVEDP), contractile function of papillary muscles, enzymatic antioxidative defense (indicated by the activities of the superoxide dismutase isoenzymes and glutathione peroxidase), and the extent of lipid peroxidation were studied. Placebo-treated rats showed cardiac hypertrophy, increased LVEDP, lower rates of contraction and relaxation, as well as a deficit in the myocardial antioxidative defense associated with increased lipid peroxide levels, when compared with sham-operated animals. Combined beta blockade and ACE inhibition improved the antioxidative defense, reduced hypertrophy and LVEDP, and enhanced rates of contraction. Thus prolonged beta blockade and ACE inhibition after infarction may decrease myocardial oxidative stress and thereby could be beneficial in heart failure.

Mechano-electric feedback in right atrium after left ventricular infarction in rats.

Left ventricular myocardial infarction (MI) can lead to alterations in hemodynamic load conditions, thereby inducing right atrial hypertrophy and dilatation associated with phenotypic modulation of cardiomyocytes, electrical abnormalities, rhythm disturbances, and atrial fibrillation. However, there is limited information on the electrophysiological basis for these events. We investigated whether atrial stretch in the setting of chronic MI modulates the electrophysiological properties of cardiomyocytes via "mechano-electric feedback", providing a mechanism for atrial arrhythmia after ventricular infarction. Five weeks after left ventricular MI (n=37), action potentials (AP) were measured in right atrial tissue preparations using a current clamp scheme, and compared to sham-operated rats (SO, n=10). Contractile activity was recorded at a preload of 1 mN, and sustained stretch was applied via a micrometer. In SO, stretch of 1.75 mN shortened repolarization at 50% and prolonged it at 90%. In MI, mechanically-induced electrical alterations were observed at a significantly lower level of stretch than in SO (0.19 mN). Sustained stretch in MI prolonged AP at 90% repolarization giving rise to stretch-activated depolarizations (SAD) near 90% repolarization (SAD90). When reaching threshold for premature APs, electrical phenomena similar to atrial fibrillations were seen in some preparations. Moreover, we observed APs with prolonged duration at 25%, 50%, and 90% repolarization where stretch induced SAD near 50%. Gadolinium used at a concentration to inhibit stretch-activated channels (40microM) suppressed mechanically-induced electrical events. In conclusion, increased susceptibility after MI to mechanical stretch may predispose atrial cardiomyocytes to arrhythmia. These mechano-electrical alterations are sensitive to gadolinium suggesting involvement of stretch-activated ion channels.

Mechanoelectric feedback after left ventricular infarction in rats.

BACKGROUND: Myocardial infarction can lead to electrical abnormalities and rhythm disturbances. However, there is limited data on the electrophysiological basis for these events. Since regional contraction abnormalities feature prominently in infarction, we investigated whether stretch of myocardium from the infarction borderzone can modulate the electrophysiological properties of cardiomyocytes via mechanoelectric feedback providing a mechanism for post-infarction arrhythmia. METHODS: Five weeks after experimental myocardial infarction (MI) in rats due to ligation of the left coronary artery (n = 26) or after sham operation (SO, n = 16), action potentials (AP) were measured in left ventricular preparations from the infarction borderzone. Sustained stretch was applied via a micrometer. RESULTS: Preparations from MI generated spontaneous electrical and contractile activity. Cardiomyocytes from MI had a comparable AP amplitude, a more negative resting membrane potential, and a prolonged AP duration (APD) when compared to SO. In SO, stretch of 150 microns increased the APD90. This was associated with stretch activated depolarizations near APD90 (SAD-90). In MI, significantly lower stretch, of only 20 microns, elicited SAD-90s, or SADs near APD50 (SAD-50). Stretch-induced events were suppressed by gadolinium, at a concentration (40 microM) normally used to inhibit stretch-activated channels. CONCLUSION: After MI, SADs are generated in the infarction borderzone at lower degrees of stretch. Increased sensitivity of the membrane potential of cardiac myocytes to mechanical stimuli may contribute to the high risk of arrhythmia after infarction. These SADs may involve the opening of stretch-activated channels.

Effects of metoprolol and ramipril on action potentials after myocardial infarction in rats.

The effects of chronic treatment with the beta-adrenoceptor antagonist metoprolol, the angiotensin converting enzyme inhibitor ramipril, their combination, or placebo on action potential configuration 6 weeks after myocardial infarction in rats were studied. Action potentials were measured in isolated left ventricular posterior papillary muscles and compared with action potentials from a sham operated group without infarction. After infarction, the action potential amplitude was reduced and this phenomenon was partially reversed by metoprolol- and ramipril-treatment. Prolonged repolarisation after infarction compared to sham operated animals was additionally delayed after metoprolol treatment. Thus, metoprolol extends the refractory period, which may counteract tachyarrhythmia.