[Care of adults with congenital heart diseases in Germany-Leading role by internal medicine specialists and general practitioners]. / Versorgung von Erwachsenen mit angeborenen Herzfehlern in Deutschland ­ tragende Rolle von Internisten und Hausärzten.

BACKGROUND: The number of adults with congenital heart disease (ACHD) is steadily increasing. The present cross-sectional study was conceived to investigate ACHD care from the perspective of patients and family practitioners (specialists for general medicine and internal medicine, general practitioners). METHODS: Questionnaire-based cross-sectional study to analyze the real care situation of ACHD in Germany from the perspective of patients and primary care physicians (PCP). RESULTS: The questionnaire was completed by 4493 ACHD (53.7% female; 41.3 ± 16.9 years) and 1055 PCP. The majority of ACHD (79.8%) visited their PCP for noncardiac health problems but also for cardiac problems. Almost all ACHD had substantial needs for medical consultation (performance, employment etc.). Of the patients 2014 (44.8%) did not know of any certified ACHD specialists or specialized centers and 2816 (62.7%) respondents were not aware of any ACHD patient organization. Of the PCPs 87.5% had cared for ACHD of all severities due to defect-typical residual and resulting symptoms. Many were not aware of any certified ACHD specialists. Only 28.5% consulted an ACHD specialist. Only 23.5% were aware of ACHD patient organizations. CONCLUSION: General practitioners are a mainstay of ACHD care in Germany. The present study shows that ACHD and their general practitioners are largely uninformed about the specialized care structures available nationwide, despite the high level of need for specialist care. In order to keep the morbidity and mortality of affected patients low, solutions must be elaborated in future to involve and integrate primary care physicians more intensively into the already existing dedicated ACHD care structures, in cooperation with specialized pediatric cardiologists, cardiologists and centers.

Prognostic markers of all-cause mortality in patients with atrial fibrillation: data from the prospective long-term registry of the German Atrial Fibrillation NETwork (AFNET).

AIMS: Atrial fibrillation (AF) is associated with a high risk of cardiovascular and non-cardiovascular death, even on anticoagulation. It is controversial, which conditions-including concomitant diseases and AF itself-contribute to this mortality. To further clarify these questions, major determinants of long-term mortality and their contribution to death were quantified in an unselected cohort of AF patients. METHODS AND RESULTS: We established a large nationwide registry comprising 8833 AF-patients with a median follow-up of 6.5 years (45 345 patient-years) and central adjudication of adverse events. Baseline characteristics of the patients were evaluated as predictors of mortality using Cox regression and C-indices for determination of predictive power. Annualized mortality was highest in the first year (6.2%) and remained high thereafter (5.2% in men and 5.5% in women). Thirty-eight percent of all deaths were cardiovascular, mainly due to heart failure or sudden death. Sex-specific age was the strongest predictor of mortality, followed by concomitant cardiovascular and non-cardiovascular conditions. These factors accounted for 25% of the total mortality beyond age and sex and for 84% of the mortality differences between AF types. Thus, the electrical phenotype of the disease at baseline contributed only marginally to prediction of mortality. CONCLUSION: Mortality is high in AF patients and arises primarily from heart failure, peripheral artery disease, chronic obstructive lung disease, chronic kidney disease, and diabetes mellitus, which, therefore, should be targeted to lower mortality. Parameters related to the electrical manifestation of AF did not have an independent impact on long-term mortality in our representative cohort.

Data mining experiments on the Angiotensin II-Antagonist in Paroxysmal Atrial Fibrillation (ANTIPAF-AFNET 2) trial: 'exposing the invisible'.

AIMS: The aims of this study include (i) pursuing data-mining experiments on the Angiotensin II-Antagonist in Paroxysmal Atrial Fibrillation (ANTIPAF-AFNET 2) trial dataset containing atrial fibrillation (AF) burden scores of patients with many clinical parameters and (ii) revealing possible correlations between the estimated risk factors of AF and other clinical findings or measurements provided in the dataset. METHODS: Ranking Instances by Maximizing the Area under a Receiver Operating Characteristics (ROC) Curve (RIMARC) is used to determine the predictive weights (Pw) of baseline variables on the primary endpoint. Chi-square automatic interaction detector algorithm is performed for comparing the results of RIMARC. The primary endpoint of the ANTIPAF-AFNET 2 trial was the percentage of days with documented episodes of paroxysmal AF or with suspected persistent AF. RESULTS: By means of the RIMARC analysis algorithm, baseline SF-12 mental component score (Pw= 0.3597), age (Pw= 0.2865), blood urea nitrogen (BUN) (Pw= 0.2719), systolic blood pressure (Pw= 0.2240), and creatinine level (Pw= 0.1570) of the patients were found to be predictors of AF burden. Atrial fibrillation burden increases as baseline SF-12 mental component score gets lower; systolic blood pressure, BUN and creatinine levels become higher; and the patient gets older. The AF burden increased significantly at age >76. CONCLUSIONS: With the ANTIPAF-AFNET 2 dataset, the present data-mining analyses suggest that a baseline SF-12 mental component score, age, systolic blood pressure, BUN, and creatinine level of the patients are predictors of AF burden. Additional studies are necessary to understand the distinct kidney-specific pathophysiological pathways that contribute to AF burden.

Early Detection of Symptomatic Paroxysmal Cardiac Arrhythmias by Trans-Telephonic ECG Monitoring: Impact on Diagnosis and Treatment of Atrial Fibrillation.

INTRODUCTION: Diagnosis of infrequent cardiac arrhythmias (CA) is often unsuccessful using resting or Holter ECG. As early detection and treatment of CA, especially atrial fibrillation (AF), has implications on patients' treatment and outcome, we investigated, whether self-guided, trans-telephonic event-recorder monitoring (Tele-ECG) improves diagnosis and influences treatment options. METHODS: Between 2009 and 2014, 790 patients (54 ± 18 years, 40% male; no history of CA: 582, known AF: 179, other CA: 29) presented with recurrent symptoms suggestive of CA and were screened by Tele-ECG (17.3 ± 26.9 days). A total of 11,775 ECGs were transmitted via a 24-hour telephone hotline including documentation of the respective symptoms. RESULTS: In 73% of patients, CA was documented at the time of symptoms: sinus tachycardia 23%, premature ventricular beats 19%, AF 14%, supraventricular tachycardia 9%, sinus bradycardia 5%, sinus arrhythmia 2%, and AV block II 1%. The mean time until the first symptomatic episode occurred was 6.9 ± 15.3 days (median 2.5 days). The first documented arrhythmia occurred on average after 7.7 ± 14.1 days (median 3 days). In patients with AF (n = 110), 44% was newly diagnosed. According to the Tele-ECG diagnosis, AF ablation was performed in 27% of these patients, 7% electrical cardioversion, and in 30% antiarrhythmic therapy was initiated. In 65% of the patients with recurrence of known AF, (re-)ablation was performed or recommended and in 16% antiarrhythmic therapy was modified. CONCLUSIONS: Tele-ECG monitoring is effective in the diagnosis of suspected symptomatic CA. A diagnosis can usually be achieved within 1 week and has implications on patients' care.

Effectiveness of Ivabradine Treatment in Different Subpopulations with Stable Angina in Clinical Practice: A Pooled Analysis of Observational Studies.

OBJECTIVES: The efficacy of ivabradine has been demonstrated in different subpopulations of stable angina patients in randomized clinical trials. This study explored its effectiveness in subpopulations seen in clinical practice as they often differ from those of randomized trials. METHODS: Data were pooled from three German observational studies with similar inclusion criteria (stable angina and heart rate ≥60 bpm). All patients received 2.5, 5, or 7.5 mg b.i.d. of ivabradine for 4 months, with or without concomitant beta-blocker. Antianginal effectiveness was analyzed in subpopulations defined by gender, age, heart rate, angina severity, use of concomitant beta-blocker, previous percutaneous coronary intervention procedure, and comorbidities (including previous myocardial infarction and diabetes). RESULTS: Treatment data were available on 8,555 patients, where therapy with ivabradine was associated with a significant reduction in the frequency of angina attacks and consumption of short-acting nitrates of 87%. Effectiveness was maintained in all investigated subpopulations, with a reduction in antianginal parameters of 82-90%. Clinical status (Canadian Cardiovascular Society class) and quality of life were also improved. Ivabradine was well tolerated in all subgroups. CONCLUSIONS: Ivabradine is effective and safe in all subpopulations of angina patients seen in clinical practice, independent of age, comorbidities, and use of beta-blocker.

Morbidity and treatment in patients with atrial fibrillation and chronic kidney disease.

Chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality but there are few studies available about atrial fibrillation, the most frequent arrhythmia in CKD, and the applied treatment. Based on the prospective German Competence NETwork on Atrial Fibrillation, data of 3138 patients with atrial fibrillation were analyzed and categorized by their estimated glomerular filtration rate (stages 1-3 and 4 plus 5). With advanced CKD, significantly more patients suffered from a more severe form of atrial fibrillation. Despite significantly higher CHADS2 scores in advanced CKD, oral anticoagulation was not prescribed more frequently while antiarrhythmic drugs and catheter ablations were used significantly less often, in contrast to more pacemaker implantations. However, in multivariate hierarchical logistic regression analyses of in-hospital treatments and complications, only hemorrhages and pacemaker implantations turned out to be independently and significantly associated with higher CKD stages. This nationwide study shows that patients with CKD and atrial fibrillation suffer from a markedly higher comorbidity. Thus, while CKD patients have received cardioversions, ablations, antiarrhythmic, or anticoagulation drugs significantly less often in their history, current treatments were not different if adjusted for multiple comorbidities. This might indicate an improvement in the often reported therapeutic nihilism in CKD.

Use of vitamin K antagonists for secondary stroke prevention depends on the treating healthcare provider in Germany - results from the German AFNET registry.

BACKGROUND: Anticoagulation using vitamin K antagonists (VKAs) significantly reduces the risk of recurrent stroke in stroke patients with atrial fibrillation (AF) and is recommended by guidelines. METHODS: The German Competence NETwork on Atrial Fibrillation established a nationwide prospective registry including 9,574 AF patients, providing the opportunity to analyse AF management according to German healthcare providers. RESULTS: On enrolment, 896 (9.4 %) patients reported a prior ischaemic stroke or transient ischaemic attack. Stroke patients were significantly older, more likely to be female, had a higher rate of cardiovascular risk factors, and more frequently received anticoagulation (almost exclusively VKA) than patients without prior stroke history. Following enrolment, 76.4 % of all stroke patients without VKA contraindications received anticoagulation, which inversely associated with age (OR 0.95 per year; 95 % CI 0.92-0.97). General practitioners/internists (OR 0.40; 95 % CI 0.21-0.77) and physicians working in regional hospitals (OR 0.47; 95 % CI 0.29-0.77) prescribed anticoagulation for secondary stroke prevention less frequently than physicians working at university hospitals (reference) and office-based cardiologists (OR 1.40; 95 % CI 0.76-2.60). The impact of the treating healthcare provider was less evident in registry patients without prior stroke. CONCLUSIONS: In the AFNET registry, anticoagulation for secondary stroke prevention was prescribed in roughly three-quarters of AF patients, a significantly higher rate than in primary prevention. We identified two factors associated with withholding oral anticoagulation in stroke survivors, namely higher age and-most prominently-treatment by a general practitioner/internist or physicians working at regional hospitals.

German Heart Report 2013.

OBJECTIVES: The 25th German Heart Report provides a comprehensive analysis of morbidity and mortality in patients with selected heart diseases as well as services and care in cardiology and cardiac surgery in Germany during the period 2011-2012. It is the result of a multidisciplinary collaboration between the German Heart Foundation, the German Cardiac Society, the German Society for Thoracic and Cardiovascular Surgery, and the German Society of Pediatric Cardiology and is based on data from different sources. In addition, trends of the period from 1995 to 2012 are presented. RESULTS: The trends in morbidity due to cardiac diseases in 2010 and previous years continued in 2011. Compared with data from 1995 to 2010, one can observe: · a slight decrease in ischemic heart disease in every age group.. · a distinct increase in valve diseases, predominantly at age >75 years.. · an increase in arrhythmias from the age of 45 years on.. · an increase in cardiac failure, especially beyond the age of 75 years.. Compared with data from 2009, the mortality rates in 2011 differ somewhat; there is: · a decrease in heart failure and coronary heart disease.. · no change in arrhythmias.. · a distinct increase in valvular heart diseases.. · an additional, small decrease in congenital heart defects.. These data are in agreement with findings from other Western countries. Coronary heart disease, the most frequent cardiac disease, has continuously decreased in frequency and mortality since 2000. The underlying reasons are discussed. CONCLUSION: This report is an important resource for all parties of the healthcare system regarding heart disease conditions and their treatment in Germany.

Efficacy of the long-acting nitro vasodilator pentaerithrityl tetranitrate in patients with chronic stable angina pectoris receiving anti-anginal background therapy with beta-blockers: a 12-week, randomized, double-blind, placebo-controlled trial.

BACKGROUND: The organic nitrate pentaerithrityl tetranitrate (PETN) has been shown to have ancillary properties that prevent the development of tolerance and endothelial dysfunction. This randomized, double-blind, placebo-controlled, multicentre study ('CLEOPATRA' study) was designed to investigate the anti-ischaemic efficacy of PETN 80 mg b.i.d. (morning and mid-day) over placebo in patients with chronic stable angina pectoris. METHODS AND RESULTS: A total of 655 patients were evaluated in the intention-to-treat population, randomized to PETN (80 mg b.i.d., n = 328) or placebo (n = 327) and completed the study. Patients underwent treadmill exercise tests at randomization, after 6 and 12 weeks of treatment. Treatment with PETN over 12 weeks did not modify the primary endpoint total exercise duration (TED, P = 0.423). In a pre-specified sub-analysis of patients with reduced exercise capacity (TED at baseline ≤9 min, n = 257), PETN appeared more effective than placebo treatment (P = 0.054). Superiority of PETN over placebo was evident in patients who were symptomatic at low exercise levels (n = 120; P = 0.017). Pentaerithrityl tetranitrate 80 mg b.i.d. was well tolerated, and the overall safety profile was comparable with placebo. CONCLUSION: Although providing no additional benefit in unselected patients with known coronary artery disease, PETN therapy, administered in addition to modern anti-ischaemic therapy, could increase exercise tolerance in symptomatic patients with reduced exercise capacity.

The German Aortic Valve Registry (GARY): in-hospital outcome.

BACKGROUND: Aortic stenosis is a frequent valvular disease especially in elderly patients. Catheter-based valve implantation has emerged as a valuable treatment approach for these patients being either at very high risk for conventional surgery or even deemed inoperable. The German Aortic Valve Registry (GARY) provides data on conventional and catheter-based aortic procedures on an all-comers basis. METHODS AND RESULTS: A total of 13 860 consecutive patients undergoing repair for aortic valve disease [conventional surgery and transvascular (TV) or transapical (TA) catheter-based techniques] have been enrolled in this registry during 2011 and baseline, procedural, and outcome data have been acquired. The registry summarizes the results of 6523 conventional aortic valve replacements without (AVR) and 3464 with concomitant coronary bypass surgery (AVR + CABG) as well as 2695 TV AVI and 1181 TA interventions (TA AVI). Patients undergoing catheter-based techniques were significantly older and had higher risk profiles. The stroke rate was low in all groups with 1.3% (AVR), 1.9% (AVR + CABG), 1.7% (TV AVI), and 2.3% (TA AVI). The in-hospital mortality was 2.1% (AVR) and 4.5% (AVR + CABG) for patients undergoing conventional surgery, and 5.1% (TV AVI) and AVI 7.7% (TA AVI). CONCLUSION: The in-hospital outcome results of this registry show that conventional surgery yields excellent results in all risk groups and that catheter-based aortic valve replacements is an alternative to conventional surgery in high risk and elderly patients.

Short-term versus long-term antiarrhythmic drug treatment after cardioversion of atrial fibrillation (Flec-SL): a prospective, randomised, open-label, blinded endpoint assessment trial.

BACKGROUND: Antiarrhythmic drugs prolong the atrial action potential and refractory period, and thereby prevent recurrent atrial fibrillation after cardioversion. The atrial action potential normalises after 2-4 weeks of sinus rhythm, suggesting that antiarrhythmic drugs might not be needed beyond that period. Therefore, we investigated whether short-term antiarrhythmic drug treatment after cardioversion is non-inferior to long-term treatment. METHODS: We enrolled patients in a prospective, randomised, open-label, blinded endpoint assessment trial between May 4, 2007, and March 12, 2010, at 44 centres in Germany. Eligible patients were adults with persistent atrial fibrillation undergoing planned cardioversion. After successful cardioversion, patients were randomly assigned in permuted blocks of six per centre to: no antiarrhythmic drug treatment (control); treatment with flecainide (200-300 mg per day) for 4 weeks (short-term treatment); or flecainide for 6 months (long-term treatment). The primary endpoint was time to persistent atrial fibrillation or death. Patients and clinicians were unmasked to group assignment and treatment. The primary outcome was assessed in a core laboratory, members of which were masked to treatment group. Patients were monitored for 6 months by daily telemetric electrocardiograph (ECG) and centrally adjudicated Holter ECG recordings whenever atrial fibrillation was noted in two consecutive ECGs. Analyses were per protocol. This trial is registered, number ISRCTN62728742. FINDINGS: After assay sensitivity was established with 4-week follow-up data from 242 patients showing that flecainide was superior to no treatment (Kaplan-Meier survival 70·2%vs 52·5%; p=0·0160), the trial continued to compare short-term versus long-term treatment. The primary outcome occurred in 120 (46%) of 261 patients receiving short-term treatment and in 103 (39%) of 263 patients receiving long-term treatment (event-free survival 48·4% [95% CI 41·9-55·0] vs 56·4% [49·1-63·6]; Kaplan-Meier estimate of difference 7·9% [-1·9 to 17·7]; p=0·2081 for non-inferiority; margin prespecified at 12%). In a post-hoc landmark analysis of patients who had not reached the primary endpoint in the first month, long-term treatment was superior to short-term treatment (Kaplan-Meier estimate of difference 14·3% [5·1-23·6]; hazard ratio 0·31 [0·18-0·56]; p=0·0001). INTERPRETATION: Short-term antiarrhythmic drug treatment after cardioversion is less effective than is long-term treatment, but can prevent most recurrences of atrial fibrillation. FUNDING: The German Federal Ministry of Education and Research, Deutsche Forschungsgemeinschaft, 3M Medica, and MEDA Pharmaceuticals.

Predictors of discordance between physicians' and patients' appraisals of health-related quality of life in atrial fibrillation patients: findings from the Angiotensin II Antagonist in Paroxysmal Atrial Fibrillation Trial.

BACKGROUND: Assessing health status is fundamental when weighing treatment options for atrial fibrillation (AF) patients. Most health-related quality-of-life (HRQoL) data stem from self-ratings, whereas treatment decisions are based upon physicians' estimations. METHODS: The degree of congruence between patients' and physicians' assessments of the patients' subjective health status was used as an indicator of good communication and shared understanding. A total of 334 patients with paroxysmal AF without significant concomitant heart diseases and their physicians were asked in a prospective blinded study to rate the patients' HRQoL. The Short Form-12 was used for self-ratings; the Short Form-8, for physician ratings. Using baseline data, intraclass correlations and Bland-Altman graphs were used to assess concordance; cross-sectional multivariate regression analyses assessed patient characteristics associated with discordance. RESULTS: On average, physicians rated their patients' HRQoL higher than patients did (∆mental component score [MCS] = -3.23, P < .0001, and ∆physical component score [PCS] = -2.21, P = .0001). Intraclass correlations and Bland-Altman graphs showed unsatisfactory concordance. Physical inactivity (∆ = 4.84) had the greatest bivariate effect on PCS discordance, and major depressive disorder (∆ = 7.01), on MCS discordance. In the regression analyses, depression was significantly associated with discord in the MCS (ß = -0.94, P < .001) and the PCS (ß = -0.37, P < .002). Sleeping disorder was associated with discord in the MCS (ß = -4.13, P < .002), and physical inactivity, with discord in the PCS (ß = -1.47, P = .006). CONCLUSIONS: In patients with AF, even in the absence of significant concomitant cardiac diseases, depression, followed by sleeping disorder and physical inactivity, was significantly associated with discordance. These findings should be considered by physicians when choosing treatment strategies.

Myeloperoxidase attracts neutrophils by physical forces.

Recruitment of polymorphonuclear neutrophils (PMNs) remains a paramount prerequisite in innate immune defense and a critical cofounder in inflammatory vascular disease. Neutrophil recruitment comprises a cascade of concerted events allowing for capture, adhesion and extravasation of the leukocyte. Whereas PMN rolling, binding, and diapedesis are well characterized, receptor-mediated processes, mechanisms attenuating the electrostatic repulsion between the negatively charged glycocalyx of leukocyte and endothelium remain poorly understood. We provide evidence for myeloperoxidase (MPO), an abundant PMN-derived heme protein, facilitating PMN recruitment by its positive surface charge. In vitro, MPO evoked highly directed PMN motility, which was solely dependent on electrostatic interactions with the leukocyte's surface. In vivo, PMN recruitment was shown to be MPO-dependent in a model of hepatic ischemia and reperfusion, upon intraportal delivery of MPO and in the cremaster muscle exposed to local inflammation or to intraarterial MPO application. Given MPO's affinity to both the endothelial and the leukocyte's surface, MPO evolves as a mediator of PMN recruitment because of its positive surface charge. This electrostatic MPO effect not only displays a so far unrecognized, catalysis-independent function of the enzyme, but also highlights a principal mechanism of PMN attraction driven by physical forces.

Pathogenic cycle between the endogenous nitric oxide synthase inhibitor asymmetrical dimethylarginine and the leukocyte-derived hemoprotein myeloperoxidase.

BACKGROUND: The nitric oxide synthase inhibitor asymmetrical dimethylarginine (ADMA) and the leukocyte-derived hemoprotein myeloperoxidase (MPO) are associated with cardiovascular diseases. Activation of monocytes and polymorphonuclear neutrophils (PMNs) with concomitant release of MPO is regulated in a nitric oxide-dependent fashion. The aim of the study was to investigate a potential 2-way interaction between ADMA and MPO. METHODS AND RESULTS: Ex vivo, ADMA uptake by isolated human PMNs, the principal source of MPO in humans, significantly impaired nitric oxide synthase activity determined by gas chromatography-mass spectrometry. In humans, short-term ADMA infusion (0.0125 mg · kg(-1) · min(-1)) significantly increased MPO plasma concentrations. Functionally, PMN exposure to ADMA enhanced leukocyte adhesion to endothelial cells, augmented NADPH oxidase activity, and stimulated PMN degranulation, resulting in release of MPO. In vivo, a 28-day ADMA infusion (250 µmol · kg(-1) · d(-1)) in C57Bl/6 mice significantly increased plasma MPO concentrations, whereas this ADMA effect on MPO was attenuated by human dimethylarginine dimethylaminohydrolase1 (hDDAH1) overexpression. Moreover, the MPO-derived reactive molecule hypochlorous acid impaired recombinant hDDAH1 activity in vitro. In MPO(-/-) mice, the lipopolysaccharide-induced increase in systemic ADMA concentrations was abrogated. CONCLUSIONS: ADMA profoundly impairs nitric oxide synthesis of PMNs, resulting in increased PMN adhesion to endothelial cells, superoxide generation, and release of MPO. In addition, MPO impairs DDAH1 activity. Our data reveal an ADMA-induced cycle of PMN activation, enhanced MPO release, and subsequent impairment of DDAH1 activity. These findings not only highlight so far unrecognized cytokine-like properties of ADMA but also identify MPO as a regulatory switch for ADMA bioavailability under inflammatory conditions.

A standardized education protocol significantly reduces traumatic injuries and syncope recurrence: an observational study in 316 patients with vasovagal syncope.

AIMS: The aim of this study was to assess the role of a non-pharmacological approach on the frequency of traumatic injuries and syncope recurrence in patients with vasovagal syncope and normal hearts. We report the experience in our syncope centre with a standardized education and teaching protocol for patients with vasovagal syncope. The treatment of vasovagal syncope is often complex and discouraging. Besides medical options, behaviour modification is a main component of therapy but has no statistical evidence to support its use. METHODS AND RESULTS: Between January 1999 and September 2006, we prospectively enrolled all patients with vasovagal syncope. The patients were counselled about the benign nature of their disease. Specific recommendations were made according to a standardized education protocol established at our syncope centre. A pre-/post-study was conducted to investigate the effectiveness of our approach on syncope recurrence and frequency of injury as the study endpoints. Complete follow-up data were available from 85% of the study population (316 of 371) after a mean time of 710 ± 286 days (mean age 50 years; standard deviation ± 18 years, 160 female). Eighty-seven patients (27.5%) had a syncope recurrence with 22 suffering an injury during syncope. During the follow-up period, the syncope burden per month was significantly reduced from 0.35 ± 0.03 at initial presentation to 0.08 ± 0.02 (P< 0.001). The frequency of traumatic syncope was significantly lower at the time of recurrence compared with the initial presentation (25 vs. 42%; McNemar's test P= 0.02). CONCLUSION: A standardized education protocol significantly reduces traumatic injuries and syncope recurrence in patients with vasovagal syncope.

Acute outcomes of MitraClip therapy for mitral regurgitation in high-surgical-risk patients: emphasis on adverse valve morphology and severe left ventricular dysfunction.

AIMS: We sought to assess the feasibility of catheter-based mitral valve repair using the MitraClip system in high-surgical-risk patients with mitral regurgitation (MR) > or =grade 3+. METHODS AND RESULTS: MitraClip therapy was performed in 51 consecutive patients [73 +/- 10 years; 34 (67%) men] with symptomatic functional [n = 35 (69%)] or organic MR [n = 16 (31%)]. Mean logistic EuroSCORE was 29 +/- 22%; Society of Thoracic Surgeons score was 15 +/- 11. Left ventricular (LV) ejection fraction was 36 +/- 17%. In 35 patients (69%), adverse mitral valve morphology and/or severe LV dysfunction were present. MitraClip implantation was successful in 49 patients (96%). Most patients [n = 34/49 (69%)] were treated with a single clip, whereas 14 patients (29%) received two clips and one patient received three clips. Mean device and fluoroscopy times were 105 +/- 65 min and 44 +/- 28 min, respectively. Procedure-related reduction in MR severity was one grade in 16 patients (31%), two grades in 24 patients (47%), and three grades in 9 patients (18%). Forty-four of the 49 successfully treated patients (90%) showed clinical improvement at discharge [NYHA functional class > or =III in 48 patients (98%) before and 16 patients (33%) after the procedure (P < 0.0001)]. There were no procedure-related major adverse events and no in-hospital mortality. CONCLUSION: Mitral valve repair using the MitraClip system was shown to be feasible in patients at high surgical risk primarily determined by an adverse mitral valve morphology and/or severe LV dysfunction.

[Unfairly Forgotten: Carl Ludwig: The Founder of Modern Physiology]. / Zu Unrecht vergessen: Carl Ludwig, Begründer der modernen Physiologie.

Cardiovascular physiology was the dominant area of research for Ludwig. He developed instruments to record hemodynamic and other physiologic events accurately, allowing him to identify previously unrecognized physiologic relationships.His classical textbook of physiology challenged traditional scientific theories and suggested new concepts. His ultimate aim was to describe nature in a mathematic manner "that in the organism no other forces are active but the common physicochemical". ("Organic physicist").His scientific program attracted medical graduates from Europe, Asia and America. Ludwig's scientific ability and personality were the major factors for the success of his research program. His intellectual generosity and unselfishness in order to promote the careers of his pupils is legendary. He put scientific research and results ahead of personal recognition. He mentored his colleagues and pupils without ever putting himself or his own interests ahead of everybody else. He decided to forgo academic recognition and did not play political games.

Long-term outcome of perimembranous VSD closure using the Nit-Occlud® Lê VSD coil system.

OBJECTIVE: This study presents data from the admission trial to show the feasibility, safety and effectiveness of the Nit-Occlud® Lê VSD in the treatment of perimembranous ventricular septal defects with an aneurysmal configuration and a diameter up to 8 mm. BACKGROUND: The majority of ventricular septal defects (VSD) are still closed surgically, while a less invasive transcatheter treatment by closure devices is available. Device-based closure is reported to be associated with the risk of complete atrio-ventricular block, especially with double-disc devices in perimembranous defects. METHODS: In six tertiary centers in Germany and Israel, an interventional closure of a periembranous VSD was attempted in 88 patients using the Nit-Occlud® Lê VSD. RESULTS: The interventional VSD closure was performed in 85 patients. Patients had a median age of 8.0 (2-65) years and a median body weight of 26.7 (10-109) kg. A complete closure of the defects was achieved in 85.4% 2 weeks after device implantation, in 88.9% after three months and in 98.6% at the 5-year follow-up. There was no incidence of death during the study nor did any patient suffer of permanent atrio-ventricular block of higher degree. Serious adverse events, by definition, are potentially life-threatening or require surgery to correct, while major serious events require medical or transcatheter intervention to correct. The study results exhibit a serious adverse event rate of 3.5% (3/85 patients) and a major adverse event rate of 5.9% (5/85 patients). CONCLUSION: The Nit-Occlud® Lê VSD coil offers the possibility of an effective and safe approach in patients with aneurysmal perimembranous ventricular septal defects.

Reduced fluoroscopy during atrial fibrillation ablation: benefits of robotic guided navigation.

BACKGROUND: Recently, a nonmagnetic robotic navigation system (RN, Hansen-Sensei) has been introduced for remote catheter manipulation. OBJECTIVE: To investigate the influence of RN combined with intuitive 3-dimensional mapping on the fluoroscopy exposure to operator and patient during pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation (PAF) in a prospective randomized trial. METHODS: Sixty patients were randomly assigned to undergo PVI either using a RN guided (group 1; n = 30, 20 male, 62 +/- 7.7 years) or conventional ablation approach (group 2; n = 30, 14 male, 61 +/- 7.6 years). A 3-dimensional mapping system (NavX) was used in both groups. RESULTS: Electrical disconnection of the ipsilateral pulmonary veins (PVs) was achieved in all patients. Use of RN significantly lowered the overall fluoroscopy time (9 +/- 3.4 vs 22 +/- 6.5 minutes; P < 0.001) and reduced the operator's fluoroscopy exposure (7 +/- 2.1 vs 22 +/- 6.5 minutes; P < 0.001). The difference in fluoroscopy duration between both groups was most pronounced during the ablation part of the procedure (3 +/- 2.4 vs 17 +/- 6.3 minutes; P < 0.001). The overall procedure duration tended to be prolonged using RN without reaching statistical significance (156 +/- 44.4 vs 134 +/- 12 minutes, P = 0.099). No difference regarding outcome was found during a midterm follow-up of 6 months (AF freedom group 1 = 73% vs 77% in group 2 [P = 0.345]). CONCLUSION: The use of RN for PVI seems to be effective and significantly reduces overall fluoroscopy time and operator's fluoroscopy exposure without affecting mid-term outcome after 6-month follow-up.

Slow wall motion rather than electrical conduction delay underlies mechanical dyssynchrony in postinfarction patients with narrow QRS complex.

INTRODUCTION: The mechanism of mechanical dyssynchrony in postinfarction patients with a narrow QRS complex is not defined but essential for cardiac resynchronization therapy (CRT). METHODS AND RESULTS: Left ventricular electrical activation and subsequent wall motion were recorded for 16 patients with ischemic cardiomyopathy during intrinsic rhythm using a modified NOGA electromechanical mapping system. Ten patients presented mechanical dyssynchrony on tissue Doppler imaging, while 6 patients served as control subjects. The local activation time (LAT) was set by the maximum downslope of the unipolar electrogram. Local wall motion time (LMT) was defined as the time needed for the catheter tip to traverse half of its maximum inward deflection during systole. LAT and LMT were measured relative to the onset of the QRS complex. Electrical activation showed a septal-to-lateral pattern in all patients with a mean endocardial activation time of 65 +/- 13 ms. Control subjects exhibited 97.5% of all LMTs <290 +/- 17 ms. Delayed motion areas (cut-off LMT > 300 ms) showed no slowing of conduction. Wall motion time corrected for differences in electrical activation (LMT-LAT) was significantly longer in delayed (289 +/- 34 ms) than in regular (204 +/- 24 ms) motion areas (P = 0.002). Delayed motion segments were hypokinetic on echocardiography and presented a lower maximum inward motion (9.9 +/- 1.1 mm) compared to regular segments (10.9 +/- 1.2 mm) on electromechanical maps (P = 0.004). Viability, however, was preserved with unipolar and bipolar voltage amplitude >7 mV and >1.5 mV for 79% of all delayed motion areas. CONCLUSION: Dyssynchronous segments of an ischemic myocardium show unimpaired local activation but slow wall motion, thereby limiting the benefit of ventricular preexcitation via CRT.