Cardiovascular outcome in type 2 diabetes and atrial fibrillation.

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.

Frequency and covariates of fear of death during myocardial infarction and its impact on prehospital delay: findings from the multicentre MEDEA Study.

BACKGROUND: Fear of death (FoD) is an exceptionally stressful symptom of ST-elevation myocardial infarction (STEMI), which received little scientific attention in recent years. We aimed to describe the prevalence and factors contributing to FoD among STEMI patients and assess the impact of FoD on prehospital delay. METHODS: This investigation was based on 592 STEMI patients who participated in the Munich Examination of Delay in Patients Experiencing Acute Myocardial Infarction (MEDEA) study. Data on sociodemographic, clinical and psycho-behavioral characteristics were collected at bedside. Multivariate logistic regression models were used to identify factors associated with FoD. RESULTS: A total of 15% of STEMI patients reported FoD (n = 88), no significant gender difference was found. STEMI pain strength [OR = 2.3 (1.4-3.9)], STEMI symptom severity [OR = 3.7 (2-6.8)], risk perception pre-STEMI [OR = 1.9 (1.2-3.2)] and negative affectivity [OR = 1.9 (1.2-3.1)] were independently associated with FoD. The median delay for those who experienced FoD was 139 min compared to 218 min for those who did not (p = 0.005). Male patients with FoD were significantly more likely to delay less than 120 min [OR = 2.11(1.25-3.57); p = 0.005], whereas in women, this association was not significant. Additionally, a clear dose-response relationship between fear severity and delay was observed. Male FoD patients significantly more often used emergency services to reach the hospital (p = 0.003). CONCLUSIONS: FoD is experienced by a clinically meaningful minority of vulnerable STEMI patients and is strongly associated with shorter delay times in men but not in women. Patients' uses of emergency services play an important role in reducing the delay in male FoD patients.

[Diabetes mellitus--risk factor for atrial fibrillation. Potential therapeutic implications]. / Diabetes mellitus--Risikofaktor für Vorhofflimmern. Potenzielle therapeutische Implikationen.

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.

Safety of intravenous ivabradine in acute ST-segment elevation myocardial infarction patients treated with primary percutaneous coronary intervention: a randomized, placebo-controlled, double-blind, pilot study.

AIMS: 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. METHODS AND RESULTS: 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 rate >80 bpm and systolic blood pressure >90 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, p<0.0001). 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. CONCLUSION: 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.

Intra-individual head-to-head comparison of Sirolimus®- and Paclitaxel®-eluting stents for coronary revascularization. A randomized, multi-center trial.

BACKGROUND: Despite the known effects of drug-eluting stents (DES), other cofactors attributed to patient characteristics affect their success. Interest focused on designing a study minimizing these factors to answer continuing concerns on the heterogeneity of response to different DESs. The study's aim was to investigate the feasibility and impact of an intra-individual comparison design in patients (pts) with two coronary artery stenosis treated with a Sirolimus- (SES) and a Paclitaxel- (PES) eluting stent. METHODS AND RESULTS: The study was conducted as a prospective, randomized, multi-center trial in 112 pts who consented to treatment with a SES and a PES. Pts were eligible if they suffered from the presence of two single primary target lesions in two different native coronary arteries. Lesions were randomized to either SES or PES treatment. The primary endpoint was in-stent luminal late loss (LLL), as determined by quantitative angiography at 8 months; clinical follow up was obtained at 1, 8, and 12 months additionally. The LLL (0.13 ± 0.28 mm SES vs. 0.26 ± 0.35 mm PES, p=0.011) showed less neointima in SES. With a predefined cut-off criterion of 0.2mm difference in LLL, 53/87 pts SES and PES were similar effective. 34/87 pts had a divergent result, 26 pts had greater benefit from SES while 8 pts had greater benefit from PES. Overall, MACE (MI, TLR, and death) occurred in 19 (17%) pts. Based on lesion analysis of 108 lesions treated with SES and 110 lesions treated with PES, 5 (4.6%) lesions with SES and 3 (2.7%) lesions with PES required repeated TLR. CONCLUSION: An intra-individual comparison design to assess differences in efficacy of different DESs is feasible, safe and achieves similar results to inter-individual studies. This study is among the first to show that failure of one DES does not necessarily implicate failure of another DES and vice versa.

The German Aortic Valve Registry (GARY): a nationwide registry for patients undergoing invasive therapy for severe aortic valve stenosis.

Background The increasing prevalence of severe aortic valve defects correlates with the increase of life expectancy. For decades, surgical aortic valve replacement (AVR), under the use of extracorporeal circulation, has been the gold standard for treatment of severe aortic valve diseases. In Germany ~12,000 patients receive isolated aortic valve surgery per year. For some time, percutaneous balloon valvuloplasty has been used as a palliative therapeutic option for very few patients. Currently, alternatives for the established surgical procedures such as transcatheter aortic valve implantation (TAVI) have become available, but there are only limited data from randomized studies or low-volume registries concerning long-time outcome. In Germany, the implementation of this new technology into hospital care increased rapidly in the past few years. Therefore, the German Aortic Valve Registry (GARY) was founded in July 2010 including all available therapeutic options and providing data from a large quantity of patients.Methods The GARY is assembled as a complete survey for all invasive therapies in patients with relevant aortic valve diseases. It evaluates the new therapeutic options and compares them to surgical AVR. The model for data acquisition is based on three data sources: source I, the mandatory German database for external performance measurement; source II, a specific registry dataset; and source III, a follow-up data sheet (generated by phone interview). Various procedures will be compared concerning observed complications, mortality, and quality of life up to 5 years after the initial procedure. Furthermore, the registry will enable a compilation of evidence-based indication criteria and, in addition, also a comparison of all approved operative procedures, such as Ross or David procedures, and the use of different mechanical or biological aortic valve prostheses.Results Since the launch of data acquisition in July 2010, almost all institutions performing aortic valve procedures in Germany joined the registry. By now, 91 sites which perform TAVI in Germany participate and more than 15,000 datasets are already in the registry.Conclusion The implementation of new or innovative medical therapies needs supervision under the conditions of a well-structured scientific project. Up to now relevant data for implementation of TAVI and long-term results are missing. In contrast to randomized controlled trials, GARY is a prospective, controlled, 5-year observational multicenter registry, and a real world investigation with only one exclusion criterion, the absence of patients' written consent.

[Patients suffering from atrial fibrillation in Germany. Characteristics, resource consumption and costs]. / Patienten mit Vorhofflimmern in Deutschland. Charakteristika, Ressourcenverbrauch und Kosten.

INTRODUCTION: Atrial fibrillation (Afib) is considered to be the most frequent form of cardiac dysrhythmia and is well known as a key risk factor for arterial thromboembolism. The incidence of Afib will increase in the future due to demographic changes as well as improved treatment options for acute and chronic heart diseases. OBJECTIVE: The primary objectives of this analysis were to describe patient characteristics, to assess the resource consumption associated with Afib and to measure costs of direct treatment as well as consequential costs. A secondary objective was to identify factors that influence the costs or the type of Afib. METHODS: The analysis is based on the representative ATRIUM register (Ambulantes Register zur Morbidität des Vorhofflimmerns, Ambulatory register on morbidity of atrial fibrillation), a prospective, multicenter cohort study in which general practitioners and family doctors documented the characteristics and resource utilization of consecutively enrolled patients. The documented resource consumption use was subsequently valued with unit costs. The presented results are focused on the baseline documentation and refer to the period 12 months before enrollment. RESULTS: A total of 3,667 patients (mean age 72.1±9.2 years, 58% men) fulfilled all inclusion criteria and were included by a total of 730 doctors. The patients had an average of 2.4±1.0 risk factors and the most common was hypertension (84% of patients). The most commonly observed comorbidities were heart failure (43%) and coronary heart disease (CHD, 35%). Medicines for oral anticoagulation (86%) and beta blockers (75%) were the most frequently prescribed drugs. A total of 1/3 of all patients received a specific kind of Afib therapy (e. g. drug conversion, cardioversion) during the past 12 months. The disease-specific mean costs of the patients were 3,274±5,134 Euro, while the acute (inpatient) treatment represented the largest proportion of these total costs (1,639±3,623 Euro). Patients with high treatment costs were significantly younger and suffered from more concomitant diseases. CONCLUSION: Atrial fibrillation is associated with significant patient-related attributable costs that are caused particularly by expenditures of inpatient stay. New, innovative treatment strategies seem to offer particular potential savings if they are able to reduce the number of hospitalizations due to Afib itself or subsequent cardiac events.

Simultaneous transcatheter aortic and mitral valve-in-valve implantation in a patient with degenerated bioprostheses and high surgical risk.

Transcatheter valve-in-valve implantation is evolving as a promising alternative to reoperative valve replacement in selected high-risk patients, considering the increasing need for redo surgery due to bioprosthetic degeneration in the future. Reoperative double valve replacements are particularly associated with an elevated surgical risk. The transapical access provides the opportunity to approach the aortic and mitral valves during one intervention. We report the case of a successful transcatheter valve-in-valve implantation in the aortic and mitral position within a single procedure.

[Diagnosis and options for reconstructive heart valve surgery in the Marfan syndrome].

Marfan syndrome is a disorder of the connective tissue that is inherited in an autosomal-dominant fashion and that is caused by mutations in the gene coding for fibrillin-1, FBN1. Although complications of the syndrome may involve the eye, the lung and the skeleton, the high mortality of untreated cases results almost exclusively from cardiovascular complications, including aortic dissection, rupture and mitral valve regurgitation. The multiorgan involvement of many of these syndromes requires multidisciplinary expert centers that can increase the average life expectancy of affected patients from only 32 years to over 60 years. The present article both reviews classical standards of managing cardiovascular manifestations and highlights the surgical approach for aortic and mitral valve surgery in Marfan patients.

[New agents for the therapy of angina pectoris]. / Neue Substanzen in der Therapie der Angina pectoris.

There is a renaissance of medical treatment of chronic angina pectoris despite of advances in interventional therapy. New drugs include nicorandil, ivabradine and ranolazine. Nicorandil dilates venous and arterial vessels via relaxation of smooth muscle cells. Since the drug has only recently been approved, the German experience is limited. Ivabradine exerts an anti-anginous effect by selective action on the sinus node with reduction of heart rate. Multiple studies have demonstrated its anti-anginal efficacy, which has also been shown if it was used as an additional therapy to classic anti-anginal treatment. Its use is reasonable as a substitute for beta-blockers or as an "add-on therapy" combined with beta-blockers, if the target heart rate for treatment of angina pectoris has not been reached. Ranolazine delays the late sodium current into the myocytes. Thereby, it improves the diastolic ventricular function and the microcirculation of the myocardium. Several large studies confirmed the anti-anginal efficacy of the drug. Currently it is used if angina pectoris still occurs under a combined treatment with different classic anti-anginal drugs.

Impact of the type of centre on management of AF patients: surprising evidence for differences in antithrombotic therapy decisions.

Atrial fibrillation (AF) patients may receive treatment from specialists or from general medicine physicians representing different levels of care within a structured health care system. This "choice" is influenced by patient flow within a health care system, patient preference, and individual access to health care resources. We analysed how the postgraduate training and work environment of treating physicians affects management decisions in AF patients. Patient characteristics and treatment decisions were analysed at the time of enrolment into the registry of the German Atrial Fibrillation NETwork (AFNET). A total of 9,577 patients were enrolled from 2004 to 2006 in 191 German centres that belonged to the following four levels of care: 13 tertiary care centres (TCC) enrolled 3,795 patients (39.6%), 58 district hospitals (DH) enrolled 2,339 patients (24.4%), 62 office-based cardiologists (OC) enrolled 2,640 patients (27.6%), and 58 general practitioners or internists (GP) enrolled 803 patients (8.4%). Patients with new-onset AF were often treated in DH. TCC treated younger patients who more often presented with paroxysmal AF. Older patients and patients in permanent AF more often received outpatient care. Consistent with recommendations, younger patients and patients with non-permanent AF received rhythm control therapy more often. In addition, the type of centre affected the decision for rhythm control. Stroke risk was similar between centre types (mean CHADS2 scores 1.6 -1.9). TCC (68.8%) and OC (73.6%) administered adequate antithrombotic therapy more often than DH (55.1%) or GP (52.0%, p<0.001 between groups). Upon multivariate analysis, enrolment by TCC or OC was associated with a 1.60 (1.20-2.12, p=0.001) fold chance for adequate antithrombotic treatment. This difference between centre types was consistent irrespective of the type of stroke risk estimation (ESC 2001 guidelines, CHADS2 score), and also consistent when the recently suggested CHA2DS2-VASc score was used to estimate stroke risk. In conclusion, management decisions in AF are influenced by the education and clinical background of treating physicians in Germany. Inpatients receive more rhythm control therapy. Adequate antithrombotic therapy is more often administered in specialist (cardiologist) centres.

Dural ectasia in individuals with Marfan-like features but exclusion of mutations in the genes FBN1, TGFBR1 and TGFBR2.

Mutations in the genes FBN1, TGFBR1, and TGFBR2 can result in heritable connective tissue disorders comprising the Marfan syndrome and the Loeys-Dietz syndrome. Dural ectasia is a characteristic manifestation of both syndromes. However, dural ectasia has not yet been investigated in connective tissue disorders that are unrelated to mutations in the FBN1, TGFBR1 or TGFBR2 genes. Here, we assessed dural ectasia in 33 individuals both with typical manifestations of heritable connective tissue disease and in whom mutations in all three genes had been excluded. We identified 19 individuals with dural ectasia (58%), who exhibited major skeletal manifestations of the Marfan syndrome more frequently than the remaining 14 persons without dural ectasia (p = 0.06). Moreover, only persons with dural ectasia fulfilled clinical criteria of the Marfan syndrome (p = 0.01). Conversely, aortic aneurysm (12 patients; p = 0.8), aortic dissection (five patients; p = 0.1), spontaneous dissection of the carotid arteries (five patients; p = 1), and mitral valve prolapse (13 patients; p = 0.4) were similarly frequent irrespective of dural ectasia. We conclude that dural ectasia is a marker for connective tissue disease which coincides with skeletal rather than with cardiovascular manifestations, and which may involve currently uncharacterized pathogenetic mechanisms and syndromes.

[Registry and studies of the German Competence Network on Atrial Fibrillation (AFNET)]. / Register und Studien des Deutschen Kompetenznetzes Vorhofflimmern (AFNET).

The German Competence Network on Atrial Fibrillation (AFNET) is a national interdisciplinary research network funded by the Federal Ministry of Education and Research (BMBF). AFNET was initiated in 2003 and aims at improving treatment of atrial fibrillation (AF), the most frequent sustained cardiac arrhythmia. AFNET has established a nationwide patient registry on diagnostics, therapy, course and complications of AF in Germany. The data analyzed to date demonstrate that patients with AF are likely to have multiple co-morbidities, such as hypertension, valvular heart disease, coronary artery disease, diabetes mellitus and advanced age. Oral anticoagulation is provided to the majority of patients in accordance with the recommendations given by guidelines. Further areas of research deal with the optimal duration of antiarrhythmic therapy following electrical cardioversion of atrial fibrillation and the value of strategies to prevent arrhythmogenic changes, such as fibrosis in the atria, for prevention of further episodes of atrial fibrillation. Additional registry projects were established for patients with catheter-based interventional therapy of atrial fibrillation and surgical ablation to define success, complications and long term results of these recently developed procedures more clearly. Data and insights gathered from these projects were used to further develop standards of care in two international conferences.

[Psychosomatic aspects of coronary heart disease]. / Psychosomatik der koronaren Herzkrankheit.

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.