[ARENA-Project atrial fibrillation in the Rhein-Neckar region]. / ARENA ­ Projekt Vorhofflimmern in der Rhein-Neckar-Region.

Atrial fibrillation (AF) is the most common form of cardiac tachyarrhythmia. It is estimated that in the Rhein-Neckar region approximately 40,000-50,000 out of 2 million people are affected. Due to demographic changes in the near future there will be a significant increase in the prevalence of AF within the next decades. The ARENA project was initiated by the Foundation Institute for Cardiac Infarction Research (IHF) Ludwigshafen in cooperation with cardiological and neurological departments of neighboring hospitals, resident doctors and pharmacies to improve the awareness and care of patients with AF. The particular aim is the prevention of stroke as one of the most dreaded complications. The project focusses on the following three subtopics: interventions, medication, migration. The aim of the intervention project is to raise awareness of AF as a risk factor for stroke and to improve the diagnostic work-up and care for patients with diagnosed or unknown AF. The subproject medication focusses on the adherence of patients with AF to the prescribed antithrombotic medication. To evaluate differences concerning patients with and without a migration background the subproject migration was initiated.

The German CPU registry: Comparison of smokers and nonsmokers.

BACKGROUND: Chest pain is a major reason for admission to an internal emergency department, and smoking is a well-known risk factor for coronary artery disease (CAD) and acute coronary syndrome (ACS). The aim of this analysis is to illustrate the differences between smokers and nonsmokers presenting to German chest pain units (CPU) in regard to patient characteristics, CAD manifestation, treatment strategy, and prognosis. METHODS: From December 2008 to March 2014, 13,902 patients who had a complete 3­month follow-up were enrolled in the German CPU registry. The analysis comprised 5796 patients with ACS and documented smoking status. RESULTS: Of all the patients in the CPU registry, 35.2% were smokers. Compared with nonsmokers, they were 13.5 years younger (58.2 vs. 71.7 years, p < 0.001), predominantly men (77.1% vs. 65.2%, p < 0.001), and were more frequently diagnosed with single-vessel disease (32.1% vs. 25.2%) as well as ST-elevation myocardial infarction (STEMI; 23.8% vs. 15.5%, p < 0.001). Although the Global Registry of Acute Coronary Events (GRACE) Risk Score for hospital mortality was lower in the group of smokers (106.1 vs. 123.3, p < 0.001), we did not observe any differences in CPU death (0.4% vs. 0.4%, p = 0.69) and CPU major adverse cardiac event (MACE) rates (3.8% vs 2.9%, p = 0.073) between the groups. In the 3­month follow-up, we documented higher mortality rates in the nonsmoker group (1.9% vs. 2.9%, p = 0.035) in correlation with the GRACE Risk Score (80.3 vs. 105.2, p < 0.001). MACE rates were similar during the follow-up (3.1% vs. 4.1%, p = 0.065). CONCLUSION: Observations from the German CPU registry demonstrate that smoking is a strong predictor of acute CAD manifestation early in life, especially STEMI. In spite of a lower GRACE Risk Score and fewer comorbidities, smokers had a rate of hospital mortality similar to the older group of nonsmokers.

Admission heart rate in relation to presentation and prognosis in patients with acute myocardial infarction. Treatment regimens in German chest pain units.

BACKGROUND: Higher heart rates on admission have been associated with poor outcomes in patients with an acute coronary syndrome in previous cohorts. Whether such a linear relationship still exists in contemporary high-level care is unclear. METHODS: Prospectively collected data from patients presenting with myocardial infarction (MI) in centers participating in the Chest Pain Unit (CPU) Registry between December 2008 and July 2014 were analyzed. Patients were classified according to their initial heart rate (I: < 50; II: 50-69; III: 70-89; IV: ≥ 90 bpm). A total of 6,168 patients out of 30,339 patients presenting to 38 centers were included in the study. RESULTS: Patients in group IV had more comorbidities, while patients in group I more often had a history of MI. Patients in the lowest heart rate group presented significantly earlier to the hospital (4 h 31 min vs. 7 h 37 min; p < 0.05) and had the highest rate of interventions. The overall survival after 3 months was significantly worse in group IV after adjusting for baseline variables. In the subgroup analysis, heart rate was a prognostic factor in the non-ST-segment elevation MI group but not in the ST-segment elevation MI group. The correlation between heart rate and major adverse cardiac events followed a J-shaped curve with worst outcomes in the lowest and highest heart rate groups. CONCLUSION: Patients admitted to a dedicated CPU with the diagnosis of MI and a heart rate > 90 bpm experience reduced survival at 3 months despite optimal treatment. Patients with bradycardia also seem to be at increased risk for cardiovascular events despite much earlier presentation and treatment.

[TRAMI (Transcatheter Mitral Valve Interventions) register. The German mitral register]. / TRAMI (Transcatheter Mitral Valve Interventions)-Register. Das Deutsche mitralklappen-register

The transcatheter mitral valve interventions (TRAMI) registry was established in 2010 in order to assess the safety and efficacy of percutaneous mitral valve therapy in Germany and to document baseline characteristics and decision-making in different subgroups of patients. The TRAMI registry is available to all German sites performing percutaneous mitral valve therapy. Follow-up is scheduled at 30 days, 1, 3, and 5 years. In addition, patients can be enrolled retrospectively without predefined times of follow-up. The vast majority of patients enrolled in TRAMI underwent MitraClip® therapy. As of March 2013, a total of 1,064 patients treated with MitraClip® have been enrolled at 21 different German sites. Preliminary results show that patients treated with MitraClip® in Germany were mainly elderly patients with significant comorbidities and high or inacceptable risk of surgery. The majority of patients had secondary mitral regurgitation and a large proportion of patients had reduced left ventricular ejection fraction (LV-EF). Nevertheless, MitraClip® was found to be safe and established risk factors for conventional cardiac mitral valve surgery, such as advanced age (≥76 years), female gender, severely reduced LV-EF (<30%) and high logistic EuroScore (≥20%) were not predictive for mortality or major complication rates. In contrast, severely reduced renal function was predictive for adverse outcome. The TRAMI registry is the largest real world cohort of patients treated with MitraClip®. As long as randomized studies in this high-risk cohort of patients are lacking, TRAMI provides important information on outcomes after MitraClip® therapy. The data are important for hypothesis generation for randomized trials and TRAMI is an important tool for quality assurance after percutaneous mitral valve therapy in Germany.

Impact of coronary artery disease on in-hospital mortality in patients with aortic valve disease. Results from the German ALKK registry.

OBJECTIVE: Although aortic valve disease (AVD) is frequently associated with coronary artery disease (CAD), little is known about the impact of significant coronary artery disease on mortality after diagnostic cardiac catheterization in patients with AVD. METHODS: We analyzed data of the coronary angiography registry of the "Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte" (ALKK) in Germany. The primary endpoint was in-hospital mortality. RESULTS: A total of 1427 consecutive patients with AVD (438 patients with CAD versus 989 patients without CAD) underwent diagnostic catheterization in 2006 in 42 hospitals. All cause in-hospital mortality was more than threefold higher in patients with CAD (16/438; 3.7%) as compared to patients without CAD (12/989; 1.2%; p < 0.01; OR 3.09, 95% CI 1.45-6.58). Even after adjustment for age, sex, presence of diabetes mellitus and renal insufficiency, in-hospital all cause mortality remained statistically significant different between the two groups (OR 2.4; 95% CI 1.09-5.28; p < 0.01). Several factors, such as transient ischemic attack/stroke, volume of contrast agent, and left heart catheter-associated complications could not be identified as possible causes for the increase in mortality. CONCLUSION: This analysis in patients with the leading diagnosis of AVD shows a significantly higher in-hospital mortality after diagnostic cardiac catheterization in case of an accompanying CAD. However, further studies are necessary to identify the driving force for the increase in mortality.

Aliskiren for the treatment of essential hypertension under real-life practice conditions: design and baseline data of the prospective 3A registry.

BACKGROUND: The renin-angiotensin system (RAS) is a key target for blood pressure control and for cardiovascular and renal protection. Aliskiren is the first-in-class direct oral inhibitor of renin that controls the rate-limiting step in the RAS cascade. So far little is known about the use and efficacy of aliskiren in the treatment of essential hypertension under clinical practice conditions. METHODS: The 3A registry was an open, prospective cohort study (observational registry) of 14,988 patients in 899 offices throughout Germany. Consecutive patients were eligible for inclusion if their physician had decided to modify their antihypertensive therapy. This included treatment with aliskiren or an angiotensin converting enzyme inhibitor (ACE-I)/angiotensin receptor blocker (ARB) or agents not blocking the RAS, alone or on top of an existing drug regimen. RESULTS: Mean age of patients was 65 years, their mean body mass index was 28.2 kg/m(2) 53.5% were men, 36% working, 90% in statutory health insurance and 26% in any disease management programme. Patients in the aliskiren and the RAS groups compared with the non-RAS group were older, more often men, had a longer history of hypertension, and had a higher prevalence of comorbidities (diabetes, chronic heart failure, ischaemic heart disease, renal disease). Mean systolic, but not diastolic blood pressure was substantially higher in the aliskiren group (158/91 mmHg vs. 154/89 mmHg in ACE-I/ARB vs. 152/89 mmHg in non-RAS). Mean number of antihypertensive drugs was higher in the aliskiren group compared with the other groups (3.0 drugs vs. 2.5 in ACE-I/ARB vs. 1.6 in non-RAS; p < 0.0001). CONCLUSIONS: In this large cohort of outpatients with hypertension, aliskiren was used mainly in patients with more severe stages of hypertension and those with concomitant diseases such as diabetes mellitus and impaired renal function. The 3A registry will provide important information about the use and efficacy of aliskiren in a real-life setting.

Health economic evaluation of the use of drug-eluting stents : First results from the Drug-Eluting Stent Registry (DES.de).

OBJECTIVE: The purpose of the economic evaluation of the German Drug-Eluting Stent (DES) registry includes the investigation of the economic impact and cost-effectiveness of DES compared to bare-metal stents (BMS) and between paclitaxel-eluting (PES) and sirolimus-eluting stents (SES). Here, methodology and initial results are presented. METHODS: Patients were recruited in 2005 and 2006 in 87 centres across Germany. Selection of PES, SES, or BMS was made at the discretion of the cardiologists in charge. Clinical, economic, and quality of life (QoL) data were collected at baseline and up to 12 months. Group comparisons were conducted using Fisher's exact and t test. RESULTS: Overall, 3,930 patients were enrolled: 3,471 (75% male, 65 ± 11 years) received DES and 458 (74% male, 67 ± 11 years) BMS. Among the DES patients, 1,821 received PES (75% male, 65 ± 10 years) and 1,600 SES (76% male, 65 ± 11 years). There were baseline differences in clinical and procedural characteristics but not in QoL. During the hospital stay, major adverse cardiac and cerebrovascular events occurred in 1.6% of DES (PES 1.9%, SES 1.1%) and 2.2% of BMS patients (BMS vs. DES, PES, and SES p = 0.327, 0.706, and 0.098, respectively). Hospital treatment costs were 4,989 ± 1,284  and 3,609 ± 924 , respectively, in DES and BMS patients (p < 0.001) with no significant difference between PES and SES. CONCLUSION: The economic evaluation of the large DES registry demonstrates increased initial hospitalisation costs associated with DES compared to BMS. Further analysis of the economic impact and cost-effectiveness of DES will provide estimates on large "real world" patient populations for decision makers and aid in reimbursement decisions of DES within the German and other health care systems.

[Registries of myocardial infarction in Germany. Consequences for drug therapy of patients with acute ST elevation myocardial infarction]. / Herzinfarktregister in Deutschland. Konsequenzen für die Arzneimitteltherapie bei Patienten mit akutem ST-Strecken-Hebungsinfarkt.

Current national and international guidelines for patients with ST elevation myocardial infarction (STEMI) are mainly based on the results of randomised clinical trials. However, it is well perceived that patients in such trials often represent a low risk population. Therefore the results of randomised clinical trials are not necessarily applicable to patients in clinical practice. This gap can be filled by prospective registries. Since the early nineties a number of prospective large registries in patients with STEMI have been performed in Germany. It could be shown that guideline adherent acute therapies and secondary prevention therapies were associated with an improvement in inhospital and mid-term outcomes. The benefit of guideline adherent therapy observed was especially high in patients with higher baseline risk. Registries are not able to replace randomised clinical trials, but can help to test if the results of these trials are comprehensible in clinical practice. Therefore prospective STEMI registries are an important part of clinical research to optimize therapies and improve outcome in patients with STEMI.

Long-term symptom improvement and patient satisfaction after AV-node ablation vs. pulmonary vein isolation for symptomatic atrial fibrillation: results from the German Ablation Registry.

BACKGROUND: We aimed to compare patient characteristics and outcome of patients who had either undergone pulmonary vein isolation (PVI) or AV-node ablation (AVN) to control AF-related symptoms. METHODS: From the German Ablation Registry, we analyzed data of 4444 patients (95%) who had undergone PVI and 234 patients (5%) with AVN. RESULTS: AVN patients were on average 10 years older than PVI patients (71 ± 10 vs. 61 ± 10 years, p < 0.001) with 33% aged > 75 years. AVN patients had significantly more cardiovascular comorbidities (diabetes 21% vs. 8%, renal insufficiency 24% vs. 3%, underlying heart disease 80% vs. 36%, severely reduced left ventricular function 28% vs. 1%, all p < 0.001). Significantly more PVI patients had paroxysmal AF (63% vs. 18%, p < 0.001), and more AVN patients had long-standing persistent AF (44% vs. 7%, p < 0.001). At 1-year follow-up, mortality in the AVN group was much higher (Kaplan-Meier estimates 9.8% vs. 0.5%). 20% of PVI patients had undergone another ablation vs. 3% AVN patients (p < 0.001). Symptomatic improvement was equally achieved in about 80%. Re-hospitalization for cardiovascular reasons occurred significantly more often in PVI vs. AVN patients (31% vs. 18%, p < 0.001). CONCLUSION: In the large German Ablation Registry, AVN ablation was performed much less frequently than PVI for symptomatic treatment of AF and typically in older patients with more comorbidity. Symptomatic improvement was similar in both groups. Hospitalizations for cardiovascular reasons were lower in AVN patients despite older age and more cardiovascular comorbidities. 20% of PVI patients had undergone at least one re-ablation.

Safety and efficacy in ablation of premature ventricular contraction: data from the German ablation registry.

BACKGROUND: Patients with frequent premature ventricular contractions (PVCs) are often highly symptomatic with significantly reduced quality-of-life. We evaluated the outcome and success of PVC ablation in patients in the German Ablation Registry. METHODS: The German Ablation Registry is a nationwide prospective multicenter database of patients who underwent an ablation procedure, initiated by the "Stiftung Institut für Herzinfarktforschung" (IHF), Ludwigshafen, Germany. Data were acquired from March 2007 to May 2011. Patients underwent PVC ablation in the enrolling ablation centers. RESULTS: A total of 408 patients (age 53.5 ± 15 years, 55 % female) undergoing ablation for PVCs were included. 32 % of patients showed a co-existing structural heart disease. Acute ablation success of the procedure was 82 % in the overall patient group. In patients without structural heart disease, acute success was significantly higher compared with patients with structural heart disease (86 vs. 74 %, p = 0.002). All patients were discharged alive after a median of 3 days. No patient suffered an acute myocardial infarction, stroke, or major bleeding. After 12 months' follow-up, 99 % of patients were still alive showing a significant different mortality between patients with structural heart disease compared with those without (2.3 vs. 0 %, p = 0.012). In addition, 76 % of patients showed significantly improved symptoms after 12 months of follow-up. CONCLUSION: Based on the data from this registry, ablation of PVCs is a safe and efficient procedure with an excellent outcome and improved symptoms after 12 months.

Clinical effects of long-term cardiac contractility modulation (CCM) in subjects with heart failure caused by left ventricular systolic dysfunction.

INTRODUCTION: Heart failure is a major cause of morbidity and mortality throughout the world. Despite advances in therapy, nearly half of patients receiving guideline-directed medical therapy remain limited by symptoms. Cardiac contractility modulation (CCM) can improve symptoms in this population, but efficacy and safety in prospective studies has been limited to 12 months of follow-up. We report on the first 2 year multi-site evaluation of CCM in patients with heart failure. METHODS: One hundred and forty-three subjects with heart failure and reduced ejection fraction were followed via clinical registry for 24 months recording NYHA class, MLWHFQ score, 6 min walk distance, LVEF, and peak VO2 at baseline and 6 month intervals as clinically indicated. Serious adverse events, and all cause as well as cardiovascular mortality were recorded. Data are presented stratified by LVEF (all subjects, LVEF <35%, LVEF ≥35%). RESULTS: One hundred and six subjects from 24 sites completed the 24 month follow-up. Baseline parameters were similar among LVEF groups. NYHA and MLWHFQ improved in all 3 groups at each time point. LVEF in the entire cohort improved 2.5, 2.9, 5.0, and 4.9% at 6, 12, 18, and 24 months, respectively. Insufficient numbers of subjects had follow-up data for 6 min walk or peak VO2 assessment, precluding comparative analysis. Serious adverse events (n = 193) were observed in 91 subjects and similarly distributed between groups with LVEF <35% and LVEF ≥35%, and similar to other device trials for heart failure. Eighteen deaths (7 cardiovascularly related) over 2 years. Overall survival at 2 years was 86.4% (95% confidence intervals: 79.3, 91.2%). CONCLUSION: Cardiac contractility modulation provides safe and effective long-term symptomatic and functional improvement in heart failure. These benefits were independent of baseline LVEF and were associated with a safety profile similar to published device trials.

Predictors of Atrial Fibrillation Recurrence after Catheter Ablation: Data from the German Ablation Registry.

Catheter ablation (CA) for atrial fibrillation (AF) has emerged as a widespread first or second line treatment option. However, up to 45% of patients (pts) show recurrence of AF within 12 month after CA. We present prospective multicenter registry data comparing characteristics of pts with and without recurrence of AF within the first year after CA. This study comprises all pts with complete follow-up one year after CA (1-y-FU; n = 3679). During 1y-FU in 1687 (45.9%) pts recurrence of AF occurred. The multivariate analysis revealed female sex and AF type prior to the procedure as predictors for AF recurrence. Furthermore, comorbidities such as valvular heart disease and renal failure as well as an early AF relapse were also predictors of AF recurrence during 1-y-FU. However, despite an AF recurrence rate of 45.9%, the majority of these pts (72.4%) reported a significant alleviation of clinical symptoms. In conclusion in pts with initially successful CA for AF female sex, AF type, in-hospital AF relapse and comorbidities such as renal failure and valvular heart disease are independent predictors for AF recurrence during 1-y-FU. However, the majority of pts deemed their interventions as successful with significant reduction of symptoms irrespective of AF.

Intercaval block in normal canine hearts : role of the terminal crest.

BACKGROUND: The intriguing monotony in the occurrence of intercaval conduction block during typical atrial flutter suggests an anatomic or electrophysiological predisposition for conduction abnormalities. METHODS AND RESULTS: To determine the location of and potential electrophysiological basis for conduction block in the terminal crest region, a high-density patch electrode (10x10 bipoles) was placed on the terminal crest and on the adjacent pectinate muscle region in 10 healthy foxhounds. With a multiplexer mapping system, local activation patterns were reconstructed during constant pacing (S(1)S(1)=200 ms) and introduction of up to 2 extrastimuli (S(2), S(3)). Furthermore, effective refractory periods were determined across the patch. If evident through online analysis, the epicardial location of conduction block was marked for postmortem verification of its endocardial projection. Marked directional differences in activation were found in the terminal crest region, with fast conduction parallel to and slow conduction perpendicular to the intercaval axis (1.1+/-0.4 versus 0.5+/-0.2 m/s, P<0.01). In the pectinate muscle region, however, conduction velocities were similar in both directions (0.5+/-0.3 versus 0.6+/-0.2 m/s, P=NS). Refractory patterns were relatively homogeneous in both regions, with local refractory gradients not >30 ms. During S(3) stimulation, conduction block parallel to the terminal crest was inducible in 40% of the dogs compared with 0% in the pectinate muscle region. CONCLUSIONS: Even in normal hearts, inducible intercaval block is a relatively common finding. Anisotropic conduction properties would not explain conduction block parallel to the intercaval axis in the terminal crest region, and obviously, refractory gradients do not seem to play a role either. Thus, the change in fiber direction associated with the terminal crest/pectinate muscle junction might form the anatomic/electrophysiological basis for intercaval conduction block.

Rate- and site-dependent effects of propafenone, dofetilide, and the new I(Ks)-blocking agent chromanol 293b on individual muscle layers of the intact canine heart.

BACKGROUND: Recent in vitro studies have demonstrated regional differences in electrophysiological properties of individual left ventricular muscle layers. Controversy exists on the relevance of these findings for the situation in vivo. Thus, this study was designed to determine whether the in vivo canine heart exhibits regional differences in left ventricular refractoriness and in the susceptibility to sodium and potassium channel blockers. METHODS AND RESULTS: In 16 dogs, 36 needle electrodes (12 mm long, 4 bipolar electrodes, interelectrode distance 2.5 mm) were inserted into the left ventricular wall. By use of a computerized multiplexer-mapping system, the spread of activation in epicardial, endocardial, and midmyocardial muscle was reconstructed during ventricular pacing at 300- and 850-ms basic cycle length (BCL). Effective refractory periods (ERPs) were determined at baseline and after application of propafenone (2 mg/kg), dofetilide (30 microg/kg), or chromanol 293b (10 mg/kg) by the extrastimulus technique (BCL 300 and 850 ms). At baseline, activation patterns and ERPs were uniform in all muscle layers. Propafenone homogeneously decreased conduction velocity and moderately prolonged ERPs without any regional differences. Dofetilide and chromanol 293b did not affect the spread of activation. Dofetilide exhibited reverse use-dependent effects on ERP, still preserving transmural homogeneity of refractoriness. Chromanol 293b led to a regionally uniform but more pronounced increase in local ERPs at faster than at slower pacing rates. CONCLUSIONS: At the heart rates applied, the in vivo canine heart does not exhibit regional differences in electrophysiological properties. Given the homogeneity of antiarrhythmic drug effects, induction of local gradients of refractoriness is obviously not a common mechanism of proarrhythmia in normal hearts.

The conduction and cardiac sympathetic systems: metabolic aspects.

Compared with the myocardium, glycolytic enzymes are reduced by 50% and mitochondrial enzymes and space by 70% in the conduction system of the calf heart. In addition, on the basis of adenosine triphosphate activities energy demands are reduced by more than 50%; this is in parallel with the reduction in myofibrillar space. The increased tolerance of the conduction system against ischemia can be explained by a reduction of energy demands and a higher proportion of (anaerobic) glycolytic as opposed to aerobic mitochondrial energy production. Among the structures of the conduction system, the sinoatrial and atrioventricular nodes are markedly susceptible to hypoxia in contrast to atrial conduction and ventricular conduction by way of the His-Purkinje system. In the isolated perfused rat heart, an increased net release of noradrenaline during the first 10 minutes of ischemia is only noted after sympathetic stimulation. During this phase, catecholamine overflow is limited by the activity of the neuronal reuptake. At a later second phase, from 15 to 40 minutes after the onset of ischemia, the mechanism of noradrenaline net release is carrier-mediated efflux inhibited by neuronal uptake blocking agents. During the third phase of ischemia, after about 40 minutes, spontaneous noradrenaline release is greatly augmented, probably as a result of leakage caused by membrane damage.

Acute myocardial infarction occurring in versus out of the hospital: patient characteristics and clinical outcome. Maximal Individual TheRapy in Acute Myocardial Infarction (MITRA) Study Group.

OBJECTIVES: We describe the baseline characteristics and clinical course of patients who had an acute myocardial infarction (AMI) during their hospital stay. BACKGROUND: In comparison with patients who had an AMI outside of the hospital (prehospital AMI), the data on patients who had an AMI in the hospital are poorly described. METHODS: Patients with an in-hospital AMI were prospectively registered in the Southwest German Maximal Individual TheRapy in Acute myocardial infarction (MITRA) study and compared with patients with prehospital AMI. RESULTS: Of 5,888 patients with AMI, 403 patients (6.8%) had an in-hospital AMI. These patients were older, more often male and sicker as compared with the patients with a prehospital AMI. They also showed a higher prevalence of concomitant diseases, such as arterial hypertension, diabetes mellitus, renal insufficiency and contraindications for thrombolysis. There was no significant difference regarding the use of reperfusion therapy, either thrombolysis (in-hospital AMI 44.2% vs. prehospital AMI 49.1%; odds ratio [OR] 0.86, 95% confidence interval [CI] 0.70 to 1.05) or primary angioplasty (9.9% vs. 8.2%; OR 1.23, 95% CI 0.88 to 1.73), or a combination of both, between the two groups. The interval from symptom onset to the start of treatment in patients receiving reperfusion therapy was 55 min for patients with an in-hospital AMI versus 180 min for patients with a prehospital AMI (p = 0.001). In-hospital death occurred in 110 (27.3%) of 403 patients with an in-hospital versus 762 (13.9%) of 5,485 patients with a prehospital AMI (OR 2.33, 95% CI 1.85 to 2.94). This was confirmed by logistic regression analysis after adjusting for other confounding variables (OR 1.67, 95% CI 1.23 to 2.24). CONCLUSIONS: In-hospital AMI occurred in 6.8% of patients. Time to intervention was shorter; however, the use of reperfusion therapy for in-hospital AMI was not different from that for prehospital AMI. In particular, primary angioplasty seems to be underused in these patients. This, as well as the selection of patients, may result in the high hospital mortality rate of 27.3%.

Multisite pacing for prevention of atrial tachyarrhythmias: potential mechanisms.

OBJECTIVES: To determine the effects of single-, dual-, triple- and quadruple-site atrial pacing on atrial activation and refractoriness in normal canine hearts. BACKGROUND: Multisite pacing has been suggested to be superior to single-site pacing for prevention of atrial tachyarrhythmias. However, the underlying electrophysiological mechanisms are undetermined at the moment, as is the rationale for the selection of pacing locations and the number of pacing sites. METHODS: In 13 normal beagle dogs, an epicardial multielectrode (128 bipoles) and a multiplexer mapping system were used to reconstruct epicardial atrial activation patterns obtained during simultaneous stimulation from up to four electrodes located in the high and low right and left atrium, respectively. For all pacing modes (single-, dual-, triple- and quadruple-site pacing), total activation times and local effective refractory periods at eight randomly selected sites as well as local recovery intervals were determined. In a subgroup of five dogs, total epicardial activation times were also obtained during single-site septal stimulation (septal group). RESULTS: Activation times and local recovery intervals were minimized by triple-site stimulation, whereas a fourth site did not produce further shortening. Septal stimulation produced epicardial activation times comparable to quadruple-site stimulation. Local refractory periods and their dispersion always remained unaffected. Functional conduction blocks apparent during single-site were found to resolve during multisite stimulation. CONCLUSIONS: Multisite pacing can prevent functional conduction blocks by multidirectional excitation and a reduction in total activation time. Triple-site and, possibly, septal pacing modes are expected to be most efficient because both minimize total activation times and maximize the multidirectionality of excitation. In spite of unaffected local refractory periods, the shortening of local recovery intervals might homogenize atrial repolarization and, thus, contribute to the preventive effects of multisite pacing.

Decreasing hospital mortality between 1994 and 1998 in patients with acute myocardial infarction treated with primary angioplasty but not in patients treated with intravenous thrombolysis. Results from the pooled data of the Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) Registry and the Myocardial Infarction Registry (MIR).

OBJECTIVES: We investigated changes in the clinical outcome of primary angioplasty and thrombolysis for the treatment of acute myocardial infarction (AMI) from 1994 to 1998. BACKGROUND: Primary angioplasty for the treatment of AMI is a sophisticated technical procedure that requires experienced personnel and optimized hospital logistics. Growing experience with primary angioplasty in clinical routine and new adjunctive therapies may have improved the outcome over the years. METHODS: The pooled data of two German AMI registries: the Maximal Individual Therapy in AMI (MITRA) study and the Myocardial Infarction Registry (MIR) were analyzed. RESULTS: Of 10,118 lytic eligible patients with AMI, 1,385 (13.7%) were treated with primary angioplasty, and 8,733 (86.3%) received intravenous thrombolysis. Patients characteristics were quite balanced between the two treatment groups, but there was a higher proportion of patients with a prehospital delay of >6 h in those treated with primary angioplasty. The proportion of an in-hospital delay of more than 90 min significantly decreased in patients treated with primary angioplasty over the years (p for trend = 0.015, multivariate odds ratio [OR] for each year of the observation period = 0.84, 95% confidence interval [CI]: 0.73-0.96) but did not change significantly in patients treated with thrombolysis. Hospital mortality decreased significantly in the primary angioplasty group (p = 0.003 for trend; multivariate OR for each year = 0.73, 95% CI: 0.58-0.93). However, for patients treated with thrombolysis, hospital mortality did not change significantly (p for trend 0.175, multivariate OR for each year: 1.02, 95% CI: 0.94- 1.11). CONCLUSIONS: Compared with thrombolysis the clinical results of primary angioplasty for the treatment of AMI improved from 1994 to 1998. This indicates a beneficial effect of the growing experience and optimized hospital logistics of this technique over the years.

Primary angioplasty versus intravenous thrombolysis in acute myocardial infarction: can we define subgroups of patients benefiting most from primary angioplasty? Results from the pooled data of the Maximal Individual Therapy in Acute Myocardial Infarction Registry and the Myocardial Infarction Registry.

OBJECTIVES: We sought to determine the effectiveness of primary angioplasty compared with thrombolysis in clinical practice. BACKGROUND: In clinical practice, primary angioplasty for the treatment of acute myocardial infarction (AMI) has not yet been proven more effective than intravenous thrombolysis, nor have subgroups of patients been identified who would perhaps benefit from primary angioplasty. METHODS: The pooled data of two AMI registries--the Maximal Individual TheRapy in Acute myocardial infarction (MITRA) study and the Myocardial Infarction Registry (MIR)--were analyzed. A total of 9,906 lytic-eligible patients with AMI, with a pre-hospital delay of < or =12 h, were treated with either primary angioplasty (n = 1,327) or thrombolysis (n = 8,579). RESULTS: Despite differences in the patients' characteristics and concomitant diseases between the two groups, the prevalence of adverse risk factors was balanced. Univariate analysis of hospital mortality showed a more favorable course for patients treated with primary angioplasty: 6.4% versus 11.3% (odds ratio [OR] 0.54, 95% confidence interval [CI] 0.43 to 0.67). This was confirmed by logistic regression analysis (multivariate OR 0.58, 95% CI 0.44 to 0.77). Primary angioplasty was associated with a lower mortality in all subgroups analyzed. We observed a significant correlation between mortality and absolute risk reduction (r = 0.82, p < 0.0001) in the different subgroups: as mortality increased, there was an increase in absolute benefit of primary angioplasty compared with thrombolysis. CONCLUSIONS: These large registry data showed the effect of primary angioplasty to be more favorable than thrombolysis for the treatment of patients with AMI in clinical practice. This effect was not restricted to special subgroups of patients. As mortality increased, the absolute benefit of primary angioplasty also increased.

Effect of nifedipine and AQ-A 39 on the sinoatrial and atrioventricular nodes of the rabbit and their antiarrhythmic action on atrioventricular nodal reentrant tachycardia.

The effects of two drugs that apparently block slow inward current--nifedipine and the new compound AQ-A 39--were studied on the isolated sinoatrial (SA) and atrioventricular (AV) nodes of the rabbit heart using intracellular microelectrodes. Nifedipine and AQ-A 39 both slowed the sinus rate associated with a decrease in the rate of diastolic depolarisation. Conduction through the AV node was consistently impaired; this effect was enhanced with increasing atrial rates or with decreasing coupling intervals of premature beats. The action potential amplitude was significantly reduced in SA nodal and upper (AN) AV nodal fibres but was not significantly affected in lower (NH) AV nodal and in atrial fibres. The maximum diastolic potential showed little or no alteration. In all fibre types studied, the action potential duration was shortened with nifedipine but was significantly prolonged with AQ-A 39. Prevention of AV nodal reentrant tachycardia by nifedipine was related to an increase in the effective refractory period of the AV node. AQ-A 39 prevented the tachycardia by both slowing of AV nodal conduction and by prolongation of action potential duration in the AV nodal and atrial compartments of the reentrant circuit associated with the appearance of different gap phenomena of the AV conduction. The maximum possible A-H interval was, however, not shortened by either drug and single atrial echo beats could still be initiated. The results suggest that nifedipine and AQ-A 39 both have a direct depressant action on the slow inward current-dependent electrical activity of the SA and AV node but have opposite effects on the repolarisation phase resulting in different antiarrhythmic mechanisms.