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Objectives The aim of this study was to determine whether noncoronary measures from cardiac computed tomography (CT) may enhance the prognostic value of this imaging technology. Background When cardiac CT is performed for quantification of coronary artery calcium (CAC) score, information on other cardiac and thoracic structures is available. Methods Participants without known cardiovascular disease from the prospective population based Heinz Nixdorf Recall study underwent noncontrast cardiac CT for CAC score quantification. From CT, epicardial adipose tissue (EAT) volume, left ventricular and left atrial (LA) axial area index, ascending and descending aortic diameters, as well as aortic valve, mitral ring, and thoracic aortic calcification (TAC) were assessed. Incident cardiovascular events included myocardial infarction, stroke, and cardiovascular death. The prognostic value of CT-derived parameters was assessed by Cox regression analysis, receiver operating characteristics, and net reclassification improvement. Results From 3,630 subjects (59 ± 8 years of age, 46% male), 241 (6.6%) developed a cardiovascular event during 9.9 ± 2.6 years of follow-up. In multivariable Cox regression analysis including Framingham Risk Score, CAC (as log[CAC + 1]), and CT parameters, LA index (hazard ratio [HR]: 1.22 [95% confidence interval [CI]: 1.05 to 1.41] per SD; p = 0.010) and EAT volume (HR: 1.15 [95% CI: 1.01 to 1.30] per SD; p = 0.031) were significantly associated with incident events. In addition, presence of TAC showed an elevated event rate (HR: 1.33 [95% CI: 0.97 to 1.81]; p = 0.08), whereas all other CT-derived parameters showed no relevant association. The LA index, EAT volume, and presence of TAC together improved the prediction of events over Framingham Risk Score and CAC in receiver operating characteristics analysis (area under the curve: 0.749 to 0.764; p = 0.011), and let to a significant net reclassification improvement (HR: 38.0%; 95% CI: 25.1% to 50.8%). Conclusion Assessment of LA index, EAT volume, and TAC from non–contrast-enhanced cardiac CT improves the prediction of incident hard cardiovascular events above CAC and established risk factors, indicating that quantification of these noncoronary measures may improve the prognostic value of this imaging technology.

Diabetes is an independent risk factor for atrial fibrillation (AF). Frequently, it is part of the metabolic syndrome cluster, which includes obesity and hypertension that are independently associated with AF. The risk appears to be higher with longer duration of diabetes and inadequate glycemic control. Patients with diabetes and AF have a substantially increased risk of death and serious cardiovascular complications compared with those in sinus rhythm. Conversely, good metabolic control appears to be associated with maintenance of rhythm after successful therapeutic conversion to sinus rhythm by catheter ablation or electrical cardioconversion of AF. AF puts patients with type 2 diabetes at a high risk of cardiovascular complications and death, which could be successfully addressed by new classes of antidiabetic agents such as incretin analogues or sglt-2 inhibitors. Thus, a diagnostic strategy that addresses the increased risk for AF is urgently recommended, in addition to diabetes monitoring in routine outpatient practice. In order to prevent thromboembolic complications, which frequently determine the prognosis for this patient population, appropriate anticoagulation remains the mainstay of therapy, whereas the prognostic value of reinstalling sinus rhythm awaits further evidence.

The relationship between atrial fibrillation and diabetes mellitus type 2 is controversial, and various studies have demonstrated conflicting results. However, the majority of larger prospective studies published during recent years demonstrated a positive correlation. After multivariate adjustment diabetes increased the risk for atrial fibrillation at least two fold. This combination is associated with substantially increased risks of death and cardiovascular events (stroke and heart failure). Atrial fibrillation in patients with diabetes mellitus type 2 identifies individuals who are likely to obtain greater benefits from glycemic control and anticoagulants as well as antihypertensive therapy.

Background: Computed tomography (CT) allows estimation of coronary artery calcium (CAC) progression. We evaluated several progression algorithms in our unselected, population-based cohort for risk prediction of coronary and cardiovascular events. Methods: In 3281 participants (45–74 years of age), free from cardiovascular disease until the second visit, risk factors, and CTs at baseline (b) and after a mean of 5.1 years (5y) were measured. Hard coronary and cardiovascular events, and total cardiovascular events including revascularization, as well, were recorded during a follow-up time of 7.8±2.2 years after the second CT. The added predictive value of 10 CAC progression algorithms on top of risk factors including baseline CAC was evaluated by using survival analysis, C-statistics, net reclassification improvement, and integrated discrimination index. A subgroup analysis of risk in CAC categories was performed. Results: We observed 85 (2.6%) hard coronary, 161 (4.9%) hard cardiovascular, and 241 (7.3%) total cardiovascular events. Absolute CAC progression was higher with versus without subsequent coronary events (median, 115 [Q1–Q3, 23–360] versus 8 [0–83], P 5y and 5-year risk factors. An excellent prognosis was found for 921 participants with double-zero CAC b =CAC 5y =0 (10-year coronary and hard/total cardiovascular risk: 1.4%, 2.0%, and 2.8%), which was for participants with incident CAC 1.8%, 3.8%, and 6.6%, respectively. When CAC b progressed from 1 to 399 to CAC 5y ≥400, coronary and total cardiovascular risk were nearly 2-fold in comparison with subjects who remained below CAC 5y =400. Participants with CAC b ≥400 had high rates of hard coronary and hard/total cardiovascular events (10-year risk: 12.0%, 13.5%, and 30.9%, respectively). Conclusions: CAC progression is associated with coronary and cardiovascular event rates, but adds only weakly to risk prediction. What counts is the most recent CAC value and risk factor assessment. Therefore, a repeat scan >5 years after the first scan may be of additional value, except when a double-zero CT scan is present or when the subjects are already at high risk.

Depression is frequent in patients with heart failure and is associated with adverse clinical outcomes. Long-term efficacy and safety of selective serotonin reuptake inhibitors in these patients are unknown.To determine whether 24 months of treatment with escitalopram improves mortality, morbidity, and mood in patients with chronic systolic heart failure and depression.The Effects of Selective Serotonin Re-Uptake Inhibition on Morbidity, Mortality, and Mood in Depressed Heart Failure Patients (MOOD-HF) study was a double-blind, placebo-controlled randomized clinical trial conducted at 16 tertiary medical centers in Germany. Between March 2009 and February 2014, patients at outpatient clinics with New York Heart Association class II-IV heart failure and reduced left ventricular ejection fraction (45%) were screened for depression using the 9-item Patient Health Questionnaire. Patients with suspected depression were then invited to undergo a Structured Clinical Interview based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) to establish the diagnosis.Patients were randomized 1:1 to receive escitalopram (10-20 mg) or matching placebo in addition to optimal heart failure therapy. Study duration was 24 months.The composite primary outcome was time to all-cause death or hospitalization. Prespecified secondary outcomes included safety and depression severity at 12 weeks of treatment (including the titration period), which were determined using the 10-item Montgomery-Åsberg Depression Rating Scale (total possible score, 0 to 60; higher scores indicate more severe depression).A total of 372 patients (mean age, 62 years; 24% female) were randomized and had taken at least 1 dose of study medication when the data and safety monitoring committee recommended the trial be stopped early. During a median participation time of 18.4 months (n = 185) for the escitalopram group and 18.7 months (n = 187) for the placebo group, the primary outcome of death or hospitalization occurred in 116 (63%) patients and 119 (64%) patients, respectively (hazard ratio, 0.99 [95% CI, 0.76 to 1.27]; P = .92). The mean Montgomery-Åsberg Depression Rating Scale sum score changed from 20.2 at baseline to 11.2 at 12 weeks in the escitalopram group and from 21.4 to 12.5 in the placebo group (between-group difference, -0.9 [95% CI,-2.6 to 0.7]; P = .26). Safety parameters were comparable between groups.In patients with chronic heart failure with reduced ejection fraction and depression, 18 months of treatment with escitalopram compared with placebo did not significantly reduce all-cause mortality or hospitalization, and there was no significant improvement in depression. These findings do not support the use of escitalopram in patients with chronic systolic heart failure and depression.isrctn.com Identifier: ISRCTN33128015.

Die medikamentose Behandlung der chronischen Angina pectoris erlebt trotz der Fortschritte der interventionellen Therapie eine Renaissance. Zu den neueren antianginosen Medikamenten zahlen Nicorandil, Ivabradin und Ranolazin. Nicorandil erweitert venose und arterielle Gefase uber eine Relaxation der glatten Gefasmuskulatur. Da die Substanz erst kurzlich zugelassen wurde, sind die Erfahrungen in Deutschland noch begrenzt. Ivabradin hemmt uber seine Wirkung am Sinusknoten selektiv die Herzfrequenz und wirkt daruber antianginos. Multiple klinische Studien haben die antianginose Wirksamkeit, auch als zusatzliche Therapie zu einer klassischen antianginosen Behandlung, bestatigt. Ein Einsatz ist sinnvoll als Alternative oder „Add-on-Therapie“ zum β-Blocker, wenn die Zielfrequenz zur Behandlung der Angina pectoris noch nicht erreicht ist. Ranolazin verzogert den spaten Natriumeinstrom in die Herzmuskelzelle und verbessert dadurch die diastolische Funktion sowie die Mikrozirkulation des Myokards. Mehrere grosere Studien haben eine antianginose Wirksamkeit der Substanz bestatigt. Sie wird derzeit dann eingesetzt, wenn unter einer Mehrfachkombination mit klassischen Antianginosa weiter Angina pectoris auftritt.

Coronary heart disease is one of the most frequent causes of death in Germany. Psychosocial factors can be considered cofactors in the development of coronary heart disease. These factors also play a particularly important role in triggering acute coronary syndrome or acute myocardial infarction. Heart disease itself can result in manifest anxiety, tendencies toward denial, and depressive disorders. Especially the latter worsen the disease course and prognosis. In addition to somatic treatment, behavioral interventions to control risk factors are available as well as psychotherapy and antidepressants. The aim of this contribution is to describe the psychosomatic aspects of coronary heart disease and to delineate the principles of a holistic approach to treatment.

In den letzten Jahren haben sich wesentliche Entwicklungen in der Diagnostik und Therapie des Vorhofflimmerns (AF) ergeben, die insbesondere den Stellenwert der interventionellen Therapie erhohen. Basierend auf der Erkenntnis, dass fokale Trigger aus den Pulmonalvenen (PV) die pradominanten Ursprungsorte des paroxysmalen Vorhofflimmerns (PAF) darstellen, hat sich die Katheterablation in Form einer elektrophysiologisch gefuhrten Diskonnektion der PV zunehmend etabliert. Das Prinzip dieser Therapie stellt die Elimination der Trigger dar, die fur die Initiierung insbesondere des PAF verantwortlich sind. Bei Patienten mit lang anhaltendem, persistierendem Vorhofflimmern (CAF) stellen die PV sehr selten das alleinige Substrat zur Initiierung und Aufrechterhaltung des Vorhofflimmerns dar, sodass die Pulmonalvenenisolation bei einem grosen Teil dieser Patienten nicht ausreichend ist. Es konnte in den letzten Jahren gezeigt werden, dass Patienten mit CAF von einer zusatzlichen Substratmodifikation profitieren. Hierbei werden die herkommlichen Ansatze in einem „stepwise ablation approach“ kombiniert angewendet mit dem Ziel der Terminierung des Vorhofflimmerns durch die Ablation. Die Katheterablation bei CAF ist derzeit noch nicht „klinisch etabliert“ und sollte nur in erfahrenen Zentren durchgefuhrt werden. Im Gegensatz dazu konnte auch im Vergleich zur medikamentosen Therapie eine Uberlegenheit der Katheterablation zur symptomatischen Behandlung von PAF gezeigt werden.

Das Vorliegen einer ischamischen Kardiomyopathie begunstigt das Auftreten von Kammertachykardien (VT). Diese stellen in den meisten Fallen eine Notfallsituation dar und konnen bei Patienten mit implantiertem Defibrillator (ICD) zu rezidivierenden Schockabgaben fuhren. Der zugrunde liegende Mechanismus ist hierbei haufig eine durch einen Myokardinfarkt bedingte Zone langsamer Leitung im Bereich des narbig veranderten Ventrikelmyokards, welche die Entstehung und Aufrechterhaltung einer Reentry-Tachykardie ermoglicht. Diese kann bei ausreichender hamodynamischer Toleranz im elektrophysiologischen Labor konventionell mittels Entrainment und Stimulationsmapping charakterisiert werden. Daruber hinaus stehen heute 3-dimensionale Mappingsysteme zur Verfugung, die das Verstandnis des Substrates und der haufig instabilen und multiplen Tachykardien verbessern helfen konnen. Die heute meist zur ICD-Therapie adjuvante Katheterablation verhindert mit einer Erfolgsrate von ca. 70–80% das erneute Auftreten von VTs, die haufig der Schockentladung bedurfen. In 10–15% der Falle ist eine Kombination von endo- und epikardialer Ablation erforderlich. Selten kann auch die Ablation mittels intrakoronarer Ethanolapplikation notwendig sein. In Zukunft konnten verbesserte Kathetertechnologie, neue Mappingsysteme und robotische Navigationsmoglichkeiten die Erfolgsraten der VT-Ablation bei Patienten mit ischamischer Kardiomyopathie weiter verbessern helfen.

The vast majority of patients with supraventricular tachycardias present with specific 12-lead surface ECG characteristics allowing the diagnosis of the underlying mechanisms prior to the invasive electrophysiological study. However, an accurate diagnosis remains challenging in a subset of patients, even when using well-established stimulation maneuvers and sophisticated conventional mapping methods. Thus, the aim of the present manuscript is to describe some cases with uncommon entities of supraventricular tachycardias where the combined interpretation of 12-lead ECG presentation and invasive electrophysiological characteristics revealed the correct diagnoses.

Vorhofflimmern ist die haufigste Arrhythmie im Erwachsenenalter. Die Therapie hat sich in den letzten Jahren erheblich verandert. Basistherapie sind β-Rezeptorenblocker und – insbesondere bei struktureller Herzkrankheit – ACE-Inhibitoren bzw. AT1-Blocker. Klasse-1C-Antiarrhythmika (Flecainid bzw. Propafenon) sollen nur bei normaler oder leicht eingeschrankter linksventrikularer Funktion eingesetzt werden. Fur therapierefraktare Patienten und solche mit deutlich eingeschrankter linksventrikularer Funktion ist Amiodaron die derzeit einzig verbleibende medikamentose Alternative. Patienten mit symptomatischen, aber seltenen Anfallen von Vorhofflimmern und normaler linksventrikularer Funktion konnen mit einer sog. „Pill-in-the-pocket-Therapie“ behandelt werden. Durch die 2006 publizierten europaischen und US-amerikanischen Leitlinien wurde die Katheterablation bei Vorhofflimmern in die „alltagliche Praxis“ eingefuhrt. Hochsymptomatische Patienten mit paroxysmalem oder kurz dauerndem anhaltendem Vorhofflimmern konnen unter folgenden Umstanden mit der Katheterablation behandelt werden: Es besteht keine schwerwiegende Herzkrankheit, der linke Vorhof ist nicht wesentlich vergrosert und es besteht Therapierefraktaritat oder Intoleranz gegenuber Antiarrhythmika. Bei allen anderen Patienten (z. B. solchen mit Herzinsuffizienz oder Herzklappenfehlern) ist die interventionelle Katheterablation von Vorhofflimmern derzeit experimentell und nur im Einzelfall als Heilversuch indiziert.

Vorhofflimmern ist bei Schrittmacherpatienten eine haufige Begleiterkrankung. Das Ziel der BACEPACE-Studie als Teilprojekt B5 des Kompetenznetzes Vorhofflimmern ist, mit einer Hybridtherapie aus praventiver Vorhofstimulation und nichtantiarrhythmischer Medikation die Vorhofflimmerbelastung (AF-burden) bei Patienten zu minimieren, die wegen symptomatischer Bradykardien einen Zweikammerschrittmacher erhalten haben und bereits paroxysmales Vorhofflimmern aufweisen. Der AF-burden wird uber die diagnostischen Schrittmacherspeicher erfasst. In den ersten 2–4 Monaten nach der Implantation eines Zweikammerschrittmachers mit praventiven getriggerten Stimulationsfunktionen (Selection 9000, Prevent AF und T 70 DR; Vitatron) erhalten die Patienten eine medikamentose Optimierung mit β-Blocker, ACE-Hemmer/AT1-Rezeptorantagonisten, der kombinierten Gabe beider Medikamente oder keine dieser Substanzen. Danach werden die Patienten auf praventiv getriggerte Stimulation (PAC SuppressionTM, Post-PAC ResponseTM, Post-Exercise ResponseTM und Post-AF ResponseTM) oder Standardeinstellung des Schrittmachers randomisiert. Die Nachbeobachtung erstreckt sich uber die folgenden 6 Monate. Der primare Studienendpunkt ist die Anzahl der Patienten mit relevanter AF-burden-Reduktion in beiden Gruppen. Als relevante Vorhofflimmerreduktion wird ein absoluter AF-burden ≤1% oder die ≥25%ige Verringerung des AF-burdens definiert. Die BACEPACE-Studie begann im Januar 2005 mit dem Patienteneinschluss und hat im Februar 2008 den geplanten Patienteneinschluss beendet.

One- and two-dimensional echocardiographic findings in 17 patients with dilated cardiomyopathy were compared with haemodynamic and angiographic results of cardiac catheterization. In a further 52 unselected patients with dilated cardiomyopathy, who had been seen as out- or in-patients over a period of two years, the frequency of intracardiac thrombi was investigated echocardiographically. A significant correlation (r = 0.66 and r = 0.68) was found between echocardiographically determined left-ventricular end-diastolic and end-systolic volumes on the one hand and volumes determined angiographically on the other. However, ventricular volumes were clearly underestimated by echocardiography. In contrast, both methods showed good agreement for the magnitude of the ejection fraction (r = 0.79). The aortic valve opening surface estimated with one-dimensional echocardiography correlated with left-ventricular ejection volume (r = 0.93). Thrombi were demonstrated in 7 out of 52 patients: 5 were located in the left, one in the right and a further one in the central pulmonary vascular system. Considering the aforementioned limitations, echocardiography is a useful method for evaluation of left-ventricular function and for demonstration of intracardiac thrombi in dilated cardiomyopathy.

Of 350 patients who had extensive non-invasive and invasive cardiological diagnostic tests, 56 had completely normal results. 24-hour ECG monitoring of the latter revealed the following ventricular arrhythmias-ventricular extrasystoles (VES): 36% without, 23% with rare ones (less than 30/h), 5.4% with more than 30/h, 25% with polytopic VES, 7.1% with paired VES and 3.6% with ventricular tachycardia. There was no preferential VES pattern. Mean duration of VES was 0.15 s. There were no VES with a prematurity index of less than 1. Extending ECG monitoring to 96 hours (10 persons without heart disease) did not reveal any more significant VES, but registering for less than 24 hours definitely underestimated the frequency of VES in persons without heart disease. In those without angiographic evidence of heart disease 36% had complex and 5.4% frequent VES. Complex arrhythmias, however, are rare in the individual subject and generally not accompanied by frequent VES. Frequent complex arrhythmias or both frequent and complex arrhythmias, as well as VES with a prematurity index less than 1, are suggestive of organic heart disease.

The diagnosis of dilated (congestive) cardiomyopathy was made in 75 patients on the basis of clinical, ECG, echo and angiographic-haemodynamic findings. Ambulatory 24-hour monitoring was undertaken in all patients. Nearly all of them (93%) had ventricular extrasystoles (VES), 35% more often than 1000/24 h. In 15% VES occurred in pairs, in 44% as ventricular tachycardia. In general, frequent VES (greater than 30/h) also came in pairs and/or as ventricular tachycardia. On the other hand, not all patients with such complex arrhythmias also had frequent VES. In about 70% of all patients with ventricular tachycardia such episodes were registered repeatedly, in more than 40% more than five tachycardia episodes per 24 hours. In the majority of patients the tachycardia consisted of three (33%), four (12%) or five (18%) consecutive ventricular complexes. All episodes of ventricular tachycardia ended spontaneously and were clinically largely silent. Apparently there was no clinically relevant correlation between frequency and severity of the arrhythmia, on the one hand, and extent of abnormal ventricular function, on the other. These findings indicate that frequent and complex ventricular arrhythmias are a characteristic feature of dilated (congestive) cardiomyopathy. If they occur in heart disease of seemingly unknown aetiology, dilated cardiomyopathy should be suspected. Preliminary findings of long-term observation indicate that patients with frequent ventricular tachycardias have a higher risk of sudden death.

127 patients, admitted within six hours of onset of symptoms of acute transmural myocardial infarction, received at first 250 000 U streptokinase intravenously over 20 min, followed by an intracoronary infusion of 250 000 U after coronary angiographic demonstration of the infarct vessel. Those in whom the infarct vessel was closed were randomized into two groups. An attempt at recanalization was made either by thrombolysis alone, through a specially developed 3F catheter (group I, 64 patients), or by thrombolysis and dilatation with 4F Gruntzig balloon catheter (group II, 63 patients). There was no significant difference between the two groups with regard to sex, age, infarct site, creatine-kinase level and interval between onset of symptoms and treatment. Re-perfusion rate for group I was 92% (59 patients), for group II 89% (56 patients). Re-occlusion during the hospital stay occurred in 10 of 59 patients in group I, in 9 of 55 in group II. Re-occlusion occurred in only 8% (3 patients) after successful dilatation, but in 35% (6 patients) after failed dilatation. In the subsequent six months further occlusions were observed in seven group I and two group II patients. Combined drug-mechanical recanalization thus increased the re-perfusion rate, shortened the infarction time and made possible full revascularization by subsequent dilatation which led to a reduction in the re-occlusion rate.

Durch Senkung des kardiovaskularen Risikofaktors Cholesterins mittels HMG-CoA-Reduktasehemmer („Statine“) konnen das Herzinfarkt- und Schlaganfallrisiko sowie die Sterblichkeit reduziert werden. Die absolute Risikoreduktion hangt von dem individuellen Risiko des Patienten, von der Hohe des LDL-Cholesterins vor Therapie und der erzielten absoluten LDL-Cholesterinsenkung ab. Dieser Tatsache wird durch die nach Risiko abgestuften Zielwerte der aktuellen Leitlinien Rechnung getragen. Das Prinzip der Ausrichtung einer Statintherapie an Lipidzielwerten betont die Bedeutung von Lebensstilmasnahmen (Ernahrung, korperliche Aktivitat) fur alle Patienten und auf jeder Stufe der Therapie. Statine sind fur die grose Mehrheit der Patienten nebenwirkungs- und risikoarm. Aktuell gibt es keinen eindeutigen klinischen Beleg fur differenzielle „pleiotrope“ Effekte zwischen verschiedenen Statinen. In Zusammenschau der vorliegenden Studien gibt es bei Einsatz von Dosierungen mit gleicher LDL-Senkung bislang keinen Beleg fur eine unterschiedliche Wirksamkeit verschiedener Statine in Bezug auf kardiovaskulare Endpunkte. Fur alle Patienten mit koronarer Herzerkrankung wird eine Senkung des LDL-Cholesterins unter 100 mg/dl durch ein Statin empfohlen.

Der Nutzen der β-Rezeptorenblocker ist besonders gut fur kardiovaskulare Risikopatienten und solche mit kardiovaskularer Begleiterkrankung belegt. Bei meist jugendlichen Patienten mit sog. essenzieller Hypertonie gibt es Argumente gegen den primaren Einsatz eines β-Blockers. Allerdings profitieren einige Patienten durchaus von einer β-Blocker-Therapie. In der Regel werden heute Patienten mit arterieller Hypertonie mit einer Kombination von Medikamenten behandelt. Daher ist die Diskussion „Primar β-Blocker oder nicht?“ haufig mehr akademisch. Bisoprolol, Carvedilol und Metoprolol verbessern die Prognose bei Patienten mit mittelschwerer und schwerer Herzinsuffizienz, die schon mit der ublichen Standardtherapie (ACE-Inhibitoren, Diuretika und evtl. Digitalis) behandelt wurden. Diese prognoseverbessernde Wirkung gilt sowohl fur Patienten mit ischamischer als auch nichtischamischer Genese der Herzinsuffizienz.

Die vaskularen Manifestationen des Diabetes mellitus sind prognostisch entscheidend fur dessen hohe Morbiditat und Mortalitat. Fur die zugrunde liegende Pathophysiologie erscheint die Generation reaktiver Sauerstoffspezies, allen voran Superoxidanionen und Wasserstoffperoxid, von zentraler Bedeutung. Superoxidanionen, gebildet durch die Entkoppelung der mitochondrialen Atmungskette, oxidieren endothelial generiertes Stickstoffmonoxid und verschlechtern so die Endothelfunktion. Superoxidanionen dismutieren spontan oder katalytisch zu Wasserstoffperoxid, dem Substrat des leukozytaren Hamproteins Myeloperoxidase, welches endothelial akkumuliert und NO in vivo oxidiert. Superoxidanionen fordern auch die Synthese fortgeschrittener Glykosilierungsprodukte, die ihrerseits wiederum vielseitige proatherogene Eigenschaften aufweisen. Schlieslich aktivieren Superoxidanionen sowie Wasserstoffperoxid redoxsensitive Transkriptionsfaktoren wie NF-κB und regulieren so die Expression proinflammatorischer Proteine wie endothelialer Adhasionsmolekule. In dieser Arbeit werden einige der wichtigsten aktuellen pathophysiologischen Konzepte der diabetischen Vaskulopathie diskutiert.

Smoking is the leading preventable cause of illness and premature death in Germany, claiming over 110,000 lives a year because it directly increases the risk of dying from heart disease, stroke, emphysema and a variety of cancers. The overwhelming majority of smokers begin tobacco use before they reach adulthood. Among those young people who smoke, the average age is now 13-14. In Germany, about 39% of male and 31% of female adults (age 18-60 years) continue to smoke, despite information about the unequivocally negative health consequences of smoking. The exact mechanisms of smoking-related vascular disease are not yet known. Smoking causes acute hemodynamic alterations such as increase in heart rate, systematic and coronary vascular resistance, myocardial contractility, and myocardial oxygen demand. These short-term effects could lower the ischemic threshold in smokers with coronary artery disease and contribute to the increased risk for acute cardiovascular events. Endothelial damage is thought to be an initiating event in atherosclerosis and early studies have demonstrated that long-term smoking has direct toxic effects with structural changes of human endothelial cells. Recent research has shown the importance of the functional role of the endothelium in regulating vascular tone, platelet-endothelial interactions, leukocyte adhesion and smooth muscle cell proliferation via synthesis and release of a variety of substances such as nitric oxide. There is strong evidence that smoking leads to endothelial dysfunction mainly by increased inactivation of nitric oxide by oxygen-derived free radicals. Smoking also increases oxidative modification of LDL and is associated with lower HDL plasma levels. Smoking induces a systemic inflammatory response with increased leukocyte count and elevation of the C-reactive protein level. Importantly, the prothrombotic effects of smoking have been repeatedly demonstrated to cause alterations in platelet function, imbalance of antithrombotic vs prothrombotic factors, and decrease of fibrinolytic activity. Given the enormous health hazard of tobacco use, complete abstinence from smoking should be achieved. Smoking cessation counselling should be given to healthy subjects and even more vigorously to patients with manifested disease. Every effort should be undertaken to prevent children and adolescents from starting to smoke. Brief tobacco dependence treatment is effective, and every smoker should be offered at least brief treatment at every office visit. More intensive treatment is more effective in producing long-term abstinence from tobacco. Nicotine replacement therapy (nicotine patches or gum), clinician-delivered social support, and skills training are the three most effective components of smoking cessation treatment. A framework for tobacco control measures is necessary to reduce tobacco consumption and exposure to tobacco smoke. Recommendations on specific tobacco control interventions are: 1. increase in tobacco taxes; 2. comprehensive tobacco advertising bans; 3. legislation prohibiting smoking in work and public places; 4. prohibiting the sales of tobacco products to persons under 18; 5. comprehensive disclosure of the physical, chemical and design characteristics of all tobacco products; 6. training of health professionals to promote smoking prevention and cessation interventions; and 7. development of a national network of smoking cessation treatment services.

Over the last years the indication for antiarrhythmic therapy has changed due to the development of other therapeutic approaches. However, antiarrhythmics are important in the acute treatment as well as the prevention of recurrent rhythm disorders. In line with the antiarrhythmic agents of class IC and III also beta-blockers, ACE inhibitors and AT (1) antagonists can be used primarily with a lower risk of severe cardiac side effects. Recent studies demonstrate that for patients with atrial fibrillation there was no benefit of rhythm control versus rate control. However, rhythm control with antiarrhythmics is beneficial in the treatment of highly symptomatic or hemodynamically compromised patients. Hybrid therapy and the "pill in the pocket"-strategy seem to be potent new therapeutic options.

BACKGROUND Percutaneous coronary interventions (PCI) are increasingly performed in elderly patients. However, it is not known whether PCI leads to symptomatic relief comparable to that in younger patients. PATIENTS AND METHODS 55 Patients aged 80 years or above with stable angina (82 +/- 2 years, 33 males, 22 females) were prospectively compared with younger patients (62 +/- 8 years) regarding their quality of life following PCI. For psychometric evaluation, the German version of the SF-36 Health Survey was used. RESULTS Prior to angioplasty, there was significant physical pain, a perception of reduced general health and a significant limitation of physical activity in both groups. The number of diseased vessels was 2.7 +/- 0.6 in octogenarian patients vs. 2.6 +/- 0.7 in control patients; interventions were performed in 1.1 +/- 0.3 vs. 1.0 +/- 0.2 vessels and in 1.3 +/- 0.7 vs. 1.3 +/- 0.5 lesions. Frequency of stent implantation was 0.9 +/- 0.3 per lesion in both groups. Success rates were comparable in both groups (94 % vs. 97 %), as well as complication rates In both groups 6 months after angioplasty, bodily pain had decreased, the perception of general health and the ability to fulfill physical role expectations had improved. The effects on bodily pain and on the ability to fulfill physical role expectations were more pronounced in octogenarian patients. CONCLUSIONS Our study shows that PCI improves quality of life in octogenarian patients with stable angina without excessive risk. The benefits of PCI were, in some aspects, even more pronounced than in younger patients.

Background Ventricular late potentials detected by the signal averaged electrocardiogram (SAECG) have been used to predict cardiac death in patients after recent myocardial infarction. The goal of this study was to investigate the prognostic significance of the SAECG in a population of chronic coronary artery disease, with and without previous myocardial infarction. Methods SAECG was recorded in 698 patients with angiographically proven coronary artery disease and analyzed by time domain analysis (TDA) and by spectral temporal mapping (STM). Cardiac death or ventricular fibrillation (= cardiac event) were used as the primary endpoint for follow-up (25 to 33 months). Results A cardiac event occurred in 46 out of 698 patients (6.6%). An abnormal SAECG using TDA was found in 43% of patients with a cardiac event, as compared to 21.7% in those without (p < 0.0005). The probability of a cardiac event during follow-up was 4.4% when TDA and STM were both normal, 9.5% and 10.2% when either STM or TDA were abnormal and 28.5% when both were abnormal. A duration of the averaged QRS complex of more than 120 ms and a left ventricular ejection fraction of less than 45% were the only independent predictors of a cardiac event. Logistic regression analysis could predict a cardiac event with a sensitivity of 54% and a specificity of 88%. Conclusions In patients with chronic coronary artery disease the duration of the signal averaged QRS complex and left ventricular ejection fraction are independent predictors of cardiac death or ventricular fibrillation.

BACKGROUND AND OBJECTIVE Symptomatic patients with multivessel coronary disease (MVD) benefit from both coronary artery bypass grafting (CABG) and percutaneous coronary angioplasty (PTCA). The >>German Angioplasty Bypass Investigation<< (GABI-I) trial randomized patients to one of these treatment strategies between 1986 and 1991. In order to evaluate the impact of current technology, in particular coronary stents, the GABI-II trial was initiated, which in 1996 and 1997 prospectively enrolled patients according to the initial GABI-I criteria. PATIENTS AND METHODS Into the study 136 consecutive patients (108 men, 28 women; 63 +/- 12 years) were included. Patients from GABI-I served as controls. RESULTS A mean of 2.1 +/- 0.5 vessels were treated per patient (vs. 1.9 +/- 0.5 vessels in the PTCA arm of GABI-I) and 63 % of the lesions were covered with stents. With respect to the primary endpoint less patients remained with a CCS class III or IV in GABI-II after 12 months (1,5 % vs. 8 % in the PTCA arm of GABI-I, p

Mibefradil is a moral calcium antagonist that is selective for the T-type voltage-operated calcium channel. It has been shown to be effective in hypertension and in stable angina. Shortly following its introduction, mibefradil was withdrawn from the market because of potentially harmful interactions with other drugs. Of special interest is the possible interaction of mibefradil with drugs which prolong the QT interval (e.g. amiodarone, quinidine, sotalol, erythromycin, desimipramine and thioridazine). This short review summarizes the effects of mibefradil on cardiac repolarization and possible implications for drug interactions with QT prolonging agents.

Background —The transmembrane sodium/hydrogen exchanger maintains myocardial cell pH integrity during myocardial ischemia but paradoxically may precipitate cell necrosis. The development of cariporide, a potent and specific inhibitor of the exchanger, prompted this investigation of the potential of the drug to prevent myocardial cell necrosis. Methods and Results —A total of 11 590 patients with unstable angina or non–ST-elevation myocardial infarction (MI) or undergoing high-risk percutaneous or surgical revascularization were randomized to receive placebo or 1 of 3 doses of cariporide for the period of risk. The trial failed to document benefit of cariporide over placebo on the primary end point of death or MI assessed after 36 days. Doses of 20 and 80 mg every 8 hours had no effect, whereas a dose of 120 mg was associated with a 10% risk reduction (98% CI 5.5% to 23.4%, P =0.12). With this dose, benefit was limited to patients undergoing bypass surgery (risk reduction 25%, 95% CI 3.1% to 41.5%, P =0.03) and was maintained after 6 months. No effect was seen on mortality. The rate of Q-wave MI was reduced by 32% across all entry diagnostic groups (2.6% versus 1.8%, P =0.03), but the rate of non–Q-wave MI was reduced only in patients undergoing surgery (7.1% versus 3.8%, P =0.005). There were no increases in clinically serious adverse events. Conclusions —No significant benefit of cariporide could be demonstrated across a wide range of clinical situations of risk. The trial documented safety of the drug and suggested that a high degree of inhibition of the exchanger could prevent cell necrosis in settings of ischemia-reperfusion.

Eine 73jahrige Patientin erwachte in der Nacht mit linksthorakalen Schmerzen und Herzklopfen. Der herbeigerufene Notarzt diagnostizierte eine hypertensive Krise. Der Blutdruck war 260/120 mm Hg, und der Notarzt verabreichte 50 mg Urapidil i.v.. Es folgte der Transport in die Klinik. In der Notaufnahme war der Blutdruck mit 190/120 mm Hg weiterhin erhoht. Die Patientin war beschwerdefrei. Das EKG zeigte keine Ischamie-typischen oder Infarkt-verdachtigen Veranderungen. Nach Gabe von 10 mg Nifedipin als Kapsel kam es zum schnellen Abfall des Blutdrucks auf 120/80 mm Hg. Es entwickelte sich eine Tachykardie, und heftige linksthorakale Schmerzen traten auf. Das EKG zeigte eine Sinustachykardie mit Ischamie-typischen ST-Streckensenkungen von 0.3 mV in den Brustwandableitungen. Die Symptomatik besserte sich nach i.v. Gabe von Nitroglycerin und Frequenzkontrolle. Das 12 h spater geschriebene EKG zeigte keine Ischamie-typischen Veranderungen. Nach Intensivierung der antihypertensiven Therapie wurde die Patientin beschwerdefrei entlassen. Bei der Patientin waren durch die Gabe von Nifedipin Angina pectoris Beschwerden und ischamietypische EKG-Veranderungen ausgelost worden. Wir diskutieren, warum wir trotz dieser Beobachtung den Gebrauch von Nifedipinkapseln bei der hypertensiven Krise fur gerechtfertigt halten.

In interventional cardiology major technical advances have been accomplished in the last 20 years. Especially, the introduction of endovascular prostheses (stents) was an important step forward. With

There is increasing evidence for a fatal interaction of myocardial ischemia, ventricular arrhythmias, and sudden cardiac death in some patients with coronary artery disease. Evidence comes from autoptic studies, from the evaluation of patients who survived an episode of sudden cardiac death, from follow-up data of these patients either treated or not by revascularization therapy and/or an implantable cardioverter-defibrillator and indicate that reducing the individual ischemic burden will be beneficial to reduce the incidence of sudden cardiac death. Studies in patients with stable and especially with unstable angina using Holter monitoring could demonstrate that there is a close and causal relationship between myocardial ischemia inducing or aggravating life-threatening ventricular arrhythmias and sudden cardiac death particularly in patients with unstable and postinfarction status. This review summarizes some of our clinical knowledge on this topic and indicates that preventive strategies for myocardial ischemia are the antiarrhythmic treatment of choice in patients with severe coronary artery disease and evidence or at risk for ischemic proarrhythmia.

Activity rate response programming depends on the physician’s experience and on the limited knowledge of patient’s daily activities. The present investigation compares a new continuous automatic adjustment of the activity rate response called rate response optimization (OPT) with fixed activity rate response programming (FIXED). At hospital discharge 37 patients with Thera DR pacemakers (Medtronic) were randomized either to FIXED (n = 20; 65 ± 12 years, male n = 12) or to OPT (n = 17; 65 ± 12 years, male n = 13). After 1 month’s follow-up occurrence of complaints related to rate-responsive pacing and the percentage of pacing were assessed. Other activity sensor parameters were programmed according to clinical judgement and similarly distributed in the two groups. Activity rate response was 7.1 ± 1.4 (FIXED) and 7.2 ± 1.7 (OPT), activity threshold was medium in 9 (FIXED) and 8 (OPT), and medium/low in 11 (FIXED) and 9 (OPT) patients, respectively. No patient with FIXED had any complaints with respect to activity-triggered rate response. One patient with OPT reported palpitations due to rapid changes in the pacing rate leading to reprogramming of the pacemaker. Atrium and ventricle were paced in 56 ± 31% (FIXED) and in 58 ± 35% (OPT; not significant) and the atrium only in 4 ± 10% (FIXED) and 0% (OPT; not significant), respectively. In the 17 patients programmed to OPT the pacemaker increased activity rate response in 5 and decreased activity rate response in 3 patients. In conclusion, as only 1 (3%) patient had complaints related to the activity rate response and fixed rate response programming according to clinical judgement already resulting in symptom-free DDDR pacing, no differences could be detected between the fixed rate response programming and rate response optimization.

During recent years there has been an increasing but still controversial discussion on the antiarrhythmic effects and overall benefit of magnesium when directed to patients with various types of ventricular tachyarrhythmias. While magnesium is considered to be a simple, safe and cost-effective approach and many casuistic and empiric reports have indicated antiarrhythmic properties of magnesium in patients with suspected or manifest ventricular arrhythmias, controlled studies proving the antiarrhythmic and overall benefit and justifying a broader use of magnesium in treating various types of ventricular arrhythmias are missing or rare. At present, antiarrhythmic properties and clinical benefit of magnesium application has only been established in patients with torsade de pointes and digitalis-induced ventricular tachyarrhythmias. In perioperative patients at risk for ventricular tachyarrhythmias and in patients suffering from manifest heart failure, data may also indicate some antiarrhythmic properties of magnesium, however, in this case with a wide consensus that the prevention of magnesium deficit is more effective and preferred in most patients over the therapeutic application of magnesium. Another group of patients who may profit from such a therapeutic approach are patients with frequent ventricular arrhythmias and stable underlying heart disease, in whom a recently published double-blind, randomized study documented an antiarrhythmic effect of a 3 week treatment with potassium and magnesium. For all other types of ventricular tachyarrhythmias, the therapeutic use of magnesium can be considered as not harmful, but also as not proven to be effective.

This multicenter, double-blind, placebo-controlled, parallel-group study was designed to assess the acute effects of intravenous mibefradil on the electrophysiologic characteristics of the human heart.Seventy-one patients referred for routine electrophysiologic testing were randomized to receive one of three intravenous treatments: placebo n = 23, 15 mg mibefradil in 15 min followed by 25 mg in 60 min (group 1, n = 24), or 35 mg mibefradil in 15 min followed by 45 mg in 60 min (group 2, n = 24). Electrophysiologic evaluations were performed prior to study drug administration and 30 min after the start of the infusion. Plasma samples were obtained at the start of the infusion and after 15, 75, and 105 min.Sinus node recovery time decreased significantly in Group 1 patients (-103 ms). Corrected sinus node recovery time in group 2 patients was 68.7 ms (P = 0.053). Compared to placebo, mibefradil produced mild but significant slowing of conduction in group 2 patients as manifested by an increase in the AH interval of 6.7 ms. Atrioventricular (AV) nodal refractoriness was increased, as indicated by a prolongation of the Wenckebach point in patients in both group 1 (32.1 ms) and group 2 (32.5 ms), compared to placebo. All adverse events were classified as mild to moderate and only one event (vasovagal attack) was considered to be treatment related.At plasma levels close to those found after chronic oral administration of 50 and 100 mg mibefradil, the higher dose produced an increase in corrected sinus node recovery time. Mibefradil also produced small but significant effects on AV nodal conduction and increased AV nodal refractoriness. Mibefradil had no effect on any other electrophysiologic parameter and was well tolerated.

Bei Patienten mit AV‐Block 2., 3. Grades und intermittierendem Vorhofflimmern bestande die Indikation fur ein VDDR‐Schrittmachersystem, wenn nicht oder nur selten im Vorhof stimuliert wurde. Deshalb wurde bei 23 Patienten mit diesen Charakteristika 1 Monat nach Implantation eines DDDR‐Schrittmachers gepruft, wie haufig sie im Vorhof stimuliert wurden; Patienten mit < 10 % Vorhofstimulation wurden solchen mit ≥ 10 % Vorhofstimulation gegenubergestellt. Falls automatischer Moduswechsel aktiviert war, wurde die Anzahl der Moduswechselepisoden als Marker fur die Haufigkeit atrialer Tachyarrhythmien erfast. Vorhofstimulation < 10 % der Zeit lag bei 7 Patienten, eine Stimulation zwischen 10 und 19 % bei 6, zwischen 20 und 29 % bei 2 und ≥ 30 % der Zeit bei 8 Patienten vor. Funf der 7 Patienten mit < 10 % Vorhofstimulation wurden im DDD‐Modus, hingegen nur 4 der 16 Patienten mit ≥ 10 % stimuliert. Patienten mit seltenerer Vorhofstimulation liesen sich nicht anhand ihrer klinischen Befunde vorhersagen. Sowohl Patienten mit < 10 % als auch solche mit ≥ 10 % Vorhofstimulation hatten jeweils in 67 % < 10 Moduswechselepisoden. Schlusfolgerungen: Im Kurzzeitverlauf nach DDDR‐Schritmacherimplatation wurden bei z.Z. ublichen Schrittmacherprogrammierungen 30 % der Patienten mit intermittierendem Vorhofflimmern und AV‐Block 2., 3. Grades selten – d.h. < 10 % der Zeit im Vorhof – stimuliert. Diese Patienten waren moglicherweise fur VDDR‐Stimulation geeignet. Seltenere Vorhofstimulation hatte keinen Einflus auf die Haufigkeit eines automatischen Moduswechsels.

Rapid heart rate lowering may be attractive in acute ST-segment elevation myocardial infarction (STEMI). Accordingly we studied the effect of intravenous ivabradine on heart rate in this setting.This was a multicenter randomized double-blind placebo-controlled trial: patients aged 40-80 years were randomized after successful primary percutaneous coronary intervention (PCI) performed within 6 h of STEMI symptom onset. Patients were in sinus rhythm and with heart rate80 bpm and systolic blood pressure90 mm Hg. They were randomly assigned (2:1 ratio) to intravenous ivabradine (n=82) (5 mg bolus over 30 s, followed by 5 mg infusion over 8 h) or matching placebo (n=42). The primary outcome measure was heart rate and blood pressure. In both groups, heart rate was reduced over 8 h, with a faster and more marked decrease on ivabradine than placebo (22.2 ± 1.3 vs 8.9 ± 1.8 bpm, p0.0001). After treatment discontinuation, heart rate was similar in both groups. Throughout the study, there was no difference in blood pressure between groups. There was no difference in cardiac biomarkers (creatine kinase (CK-MB), troponin T and troponin I). On echocardiography performed at baseline and post treatment (median 1.16 days), final left ventricular volumes were lower in the ivabradine group both for left ventricular end-diastolic volume (LVEDV) (87.1 ± 28.2 vs 117.8 ± 21.4 ml, p=0.01) and left ventricular end-systolic volume (LVESV) (42.5 ± 19.0 versus 59.1 ± 11.3 ml, p=0.03) without differences in volume change or left ventricular ejection fraction.This pilot study shows that intravenous ivabradine may be used safely to slow the heart rate in STEMI. Further studies are needed to characterize its effect on infarct size, left ventricular function and clinical outcomes in this population.

Worldwide several systems for Digital Subtraction Angiography in energy subtraction mode (dichromography) with synchrotron radiation are developed. Two of the systems–the system NIKOS in the Hamburger Synchrotronstrahlungslabor HASYLAB in Hamburg and the system in Brookhaven–allow investigations of patients. The aim of the work is to visualize coronary arteries down to 1 mm diameter with an iodine mass density of 1 mg/cm2, thus allowing non-invasive investigations by intravenous application of the contrast medium. The two images for subtraction are simultaneously taken with photon energies just below and above the iodine K-edge (33.17 keV) in a line scan mode. In principle the system NIKOS consists of six main parts: A 20-pole wiggler with a total length of 2.4 m and a field of 1.26 T is installed in the storage ring DORIS at DESY in Hamburg. In a two beam monochromator two bent perfect Si(111) crystals in Laue geometry are used for filtering the quasi-monochromatic beams with a bandwidth of 180 eV out of the white synchrotron radiation beam. In a safety system three independent very fast beam shutters are installed which close within less than 10 ms at any malfunction of the system. Because the line scan mode is used a scanning device moves the patient with up to 50 cm/s through the two monochromatic beams. As a detector a two-line ionization chamber with a spatial resolution of 0.4 mm is installed. The chamber has a dynamic range of 39,000:1 and reads a line within 0.73 ms. The quantum efficiency for 33 keV photons is 85%. The computer system is used for control of the system, data acquisition, image processing and presentation. Since 1990 thirty patients were studied with the system NIKOS. In all cases follow-up investigations after interventions like bypass surgery, angioplasty or rotablation were performed. Intravenous angiograms from investigations with version III of the system are presented.

BACKGROUND AND AIM OF THE STUDY As increasing impedance of the pacing impulse decreases pacing current, high pacing impedance lowers pacing current and subsequently prolongs pacemaker longevity. The present assumption of a standard 500 ohms impedance disregards interindividual differences. In the present study, the interindividual range of pacing impedance was assessed at implantation. Additionally clinical parameters of patients with low pacing impedance were compared to those of patients with high values. PATIENTS AND METHODS The same lead and the same pacemaker (CapSure VDD; Thera VDD; Medtronic) were implanted in 126 patients (79 men, 47 women, mean age 65 +/- 16 years). Patients with an impedance below or similar to the median were compared to patients with an impedance above the median in respect to clinical (age, gender, arterial hypertension, cardiac diseases such as coronary heart disease, valvular heart disease, cardiomyopathy) and electrical parameters (pacing threshold at 0.5 ms pulse duration, R-wave amplitude). RESULTS Mean impedance was 687 +/- 121 ohms with a range from 333 to 1040 ohms and a median of 670 ohms. 64 patients had an impedance 670 ohms. Mean age, gender and the occurrence of arterial hypertension were similar in the two groups. Cardiac diseases occurred significantly (P < 0.01) more often in patients with lower (n = 23) than with higher impedance (n = 9). Intraoperative pacing thresholds and R-wave amplitudes were not different between the two groups. CONCLUSIONS The range of pacing impedance was 707 ohms for the studied lead. Under consideration of permanent pacing with 2.5 V pulse amplitude and 0.5 ms pulse duration this would vary expected longevity of the implanted pacemaker from 7.8 to 9.3 years. Patients with lower impedance more often had cardiac diseases than patients with higher impedance.

Hypertensive heart disease is increasingly considered to be a strong and independent risk factor for sudden cardiac death. Ventricular tachyarrhythmias in these patients are common and mainly the result of electrophysiologic abnormalities and increased electrical vulnerability of the hypertrophic myocardium. However, proarrhythmia in the hypertrophic heart often is facilitated and aggravated by electrolyte disturbances, the sympathoadrenergic tone, transient blood pressure crisis, and especially by the occurrence of myocardial ischemia. Myocardial ischemia in the setting of hypertensive heart disease may result from stenotic lesions in large and/or small coronary artery vessels and, in the absence of both, will result from the altered cellular oxygen supply and consumption in the hypertrophic myocardium. Recent studies have shown that acute and transient myocardial ischemia are common in many hypertensives, often fail to be symptomatic, and that the dynamic interaction of left ventricular hypertrophy, transient myocardial ischemia, and ventricular tachyarrhythmias may provide a crucial link for the high incidence of sudden cardiac death in patients with hypertensive heart disease.