Jochen Senges

Transcatheter aortic valve implantation: first results from a multi-centre real-world registry

AIMS Treatment of elderly symptomatic patients with severe aortic stenosis and co-morbidities is challenging. Transcatheter aortic valve interventions [balloon valvuloplasty and transcatheter aortic valve implantation (TAVI)] are evolving as alternative treatment options to surgical valve replacement. We report the first results of the prospective multi-centre German Transcatheter Aortic Valve Interventions-Registry. METHODS AND RESULTS Between January 2009 and December 2009, a total of 697 patients (81.4 ± 6.3 years, 44.2% males, and logistic EuroScore 20.5 ± 13.2%) underwent TAVI. Pre-operative aortic valve area was 0.6 ± 0.2 cm² with a mean transvalvular gradient of 48.7 ± 17.2 mmHg. Transcatheter aortic valve implantation was performed percutaneously in the majority of patients [666 (95.6%)]. Only 31 (4.4%) procedures were done surgically: 26 (3.7%) transapically and 5 (0.7%) transaortically. The Medtronic CoreValve™ prosthesis was used in 84.4%, whereas the Sapien Edwards™ prosthesis was used in the remaining cases. Technical success was achieved in 98.4% with a post-operative mean transaortic pressure gradient of 5.4 ± 6.2 mmHg. Any residual aortic regurgitation was observed in 72.4% of patients, with a significant aortic insufficiency (≥Grade III) in only 16 patients (2.3%). Complications included pericardial tamponade in 1.8% and stroke in 2.8% of patients. Permanent pacemaker implantation after TAVI became necessary in 39.3% of patients. In-hospital death rate was 8.2%, and the 30-day death rate 12.4%. CONCLUSION In this real-world registry of high-risk patients with aortic stenosis, TAVI had a high success rate and was associated with moderate in-hospital complications. However, careful patient selection and continued hospital selection seem crucial to maintain these results.

Annual Rate of Transvenous Defibrillation Lead Defects in Implantable Cardioverter-Defibrillators Over a Period of >10 Years

Background— The number of patients with longer follow-up after implantation of an implantable cardioverter-defibrillator is increasing continuously. Defibrillation lead failure is a typical long-term complication. Therefore, the long-term reliability of implantable cardioverter-defibrillator leads has become an increasing concern. The aim of the present study was to assess the annual rate of transvenous defibrillation lead defects related to follow-up time after lead implantation. Methods and Results— A total of 990 consecutive patients who underwent first implantation of an implantable cardioverter-defibrillator between 1992 and May 2005 were analyzed. Median follow-up time was 934 days (interquartile range, 368 to 1870). Overall, 148 defibrillation leads (15%) failed during the follow-up. The estimated lead survival rates at 5 and 8 years after implantation were 85% and 60%, respectively. The annual failure rate increased progressively with time after implantation and reached 20% in 10-year-old leads (P<0.001). Lead defects affected newer as well as older models. Patients with lead defects were 3 years younger at implantation and more often female. Multiple lead implantation was associated with a trend to a higher rate of defibrillation lead defects (P=0.06). The major lead complications were insulation defects (56%), lead fractures (12%), loss of ventricular capture (11%), abnormal lead impedance (10%), and sensing failure (10%). Conclusions— An increasing annual lead failure rate is noted primarily during long-term follow-up and reached 20% in 10-year-old leads. Patients with lead defects are younger and more often female.

Defibrillator Implantation Early after Myocardial Infarction

BACKGROUND The rate of death, including sudden cardiac death, is highest early after a myocardial infarction. Yet current guidelines do not recommend the use of an implantable cardioverter-defibrillator (ICD) within 40 days after a myocardial infarction for the prevention of sudden cardiac death. We tested the hypothesis that patients at increased risk who are treated early with an ICD will live longer than those who receive optimal medical therapy alone. METHODS This randomized, prospective, open-label, investigator-initiated, multicenter trial registered 62,944 unselected patients with myocardial infarction. Of this total, 898 patients were enrolled 5 to 31 days after the event if they met certain clinical criteria: a reduced left ventricular ejection fraction (< or = 40%) and a heart rate of 90 or more beats per minute on the first available electrocardiogram (ECG) (criterion 1: 602 patients), nonsustained ventricular tachycardia (> or = 150 beats per minute) during Holter monitoring (criterion 2: 208 patients), or both criteria (88 patients). Of the 898 patients, 445 were randomly assigned to treatment with an ICD and 453 to medical therapy alone. RESULTS During a mean follow-up of 37 months, 233 patients died: 116 patients in the ICD group and 117 patients in the control group. Overall mortality was not reduced in the ICD group (hazard ratio, 1.04; 95% confidence interval [CI], 0.81 to 1.35; P=0.78). There were fewer sudden cardiac deaths in the ICD group than in the control group (27 vs. 60; hazard ratio, 0.55; 95% CI, 0.31 to 1.00; P=0.049), but the number of nonsudden cardiac deaths was higher (68 vs. 39; hazard ratio, 1.92; 95% CI, 1.29 to 2.84; P=0.001). Hazard ratios were similar among the three groups of patients categorized according to the enrollment criteria they met (criterion 1, criterion 2, or both). CONCLUSIONS Prophylactic ICD therapy did not reduce overall mortality among patients with acute myocardial infarction and clinical features that placed them at increased risk. (ClinicalTrials.gov number, NCT00157768.)

OMEGA, a Randomized, Placebo-Controlled Trial to Test the Effect of Highly Purified Omega-3 Fatty Acids on Top of Modern Guideline-Adjusted Therapy After Myocardial Infarction

Background— There is no randomized, double-blind trial testing the prognostic effect of highly purified omega-3 fatty acids in addition to current guideline-adjusted treatment of acute myocardial infarction. Methods and Results— OMEGA is a randomized, placebo-controlled, double-blind, multicenter trial testing the effects of omega-3-acid ethyl esters-90 (1 g/d for 1 year) on the rate of sudden cardiac death in survivors of acute myocardial infarction, if given in addition to current guideline-adjusted treatment. Secondary end points were total mortality and nonfatal clinical events. Patients (n=3851; female, 25.6%; mean age, 64.0 years) were randomized in 104 German centers 3 to 14 days after acute myocardial infarction from October 2003 until June 2007. Acute coronary angiography was performed in 93.8% and acute percutaneous coronary intervention in 77.8% of all patients. During a follow-up of 365 days, the event rates were (omega and control groups) as follows: sudden cardiac death, 1.5% and 1.5% (P=0.84); total mortality, 4.6% and 3.7% (P=0.18); major adverse cerebrovascular and cardiovascular events, 10.4% and 8.8% (P=0.1); and revascularization in survivors, 27.6% and 29.1% (P=0.34). Conclusions— Guideline-adjusted treatment of acute myocardial infarction results in a low rate of sudden cardiac death and other clinical events within 1 year of follow-up, which could not be shown to be further reduced by the application of omega-3 fatty acids. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00251134.

Aortic regurgitation after transcatheter aortic valve implantation: incidence and early outcome. Results from the German transcatheter aortic valve interventions registry

Background Significant aortic regurgitation (AR) is rare following surgical aortic valve replacement and has been associated with worse outcome. Following transcatheter aortic valve implantation (TAVI), AR is common, but little is known about its determinants and its effect on clinical outcome. Objective To evaluate early outcome and risk factors possibly associated with AR after TAVI. Methods Data were analysed from 690 patients with severe aortic stenosis treated with TAVI enrolled in the prospective multicentre German transcatheter aortic valve interventions registry. The occurrence of AR was evaluated angiographically after device deployment and removal of the catheter and guidewire. Significant AR was defined as AR≥2/4. Results The study populations mean age was 81.4±6.3 years and men represented 44%. The mean logistic Euroscore was 20.4±13.1%. Overall, 84% of patients received the Medtronic CoreValve system and 16% received the Edwards Sapien valve. Significant AR occurred in 119 patients (17.2%). Factors independently associated with significant AR were aortic valve area (adjusted OR=0.10), annulus measurement by transoesophageal echocardiography (adjusted OR=1.94), male gender (adjusted OR=1.80), cardiogenic shock (adjusted OR=1.94) and renal failure (adjusted OR=0.53). In-hospital death rates were significantly higher in patients with significant AR than in those with no/mild AR (15.1% vs 6.7%, OR=2.50, 95% CI 1.37 to 4.55), as were rates of low cardiac output (20% vs 4.4%) and respiratory failure (16.5% vs 7.1%). Using multivariate analysis, the presence of post-procedural AR≥2/4 remained a strong independent predictor of in-hospital death (adjusted OR=2.43, 95% CI 1.22 to 4.85). Conclusion Significant AR after TAVI is common and is associated with increased in-hospital mortality. Long-term follow-up is critical to further define the impact of residual AR on clinical outcome. Until these data become available, every effort should be made to prevent and treat this complication.

Rationale and design of the LURIC study--a resource for functional genomics, pharmacogenomics and long-term prognosis of cardiovascular disease.

BACKGROUND AND AIM Coronary artery disease (CAD), arterial hypertension and Type 2 diabetes mellitus are common polygenetic disorders which have a major impact on public health. Disease prevalence and progression to cardiovascular complications, such as myocardial infarction (MI), stroke or heart failure, are the product of environment and gene interaction. The LUdwigshafen RIsk and Cardiovascular Health (LURIC) study aims to provide a well-defined resource for the study of environmental and genetic risk factors, and their interactions, and the study of functional relationships between gene variation and biochemical phenotype (functional genomics) or response to medication (pharmacogenomics). Long-term follow-up on clinical events will allow us to study the prognostic importance of common genetic variants (polymorphisms) and plasma biomarkers. SETTING Cardiology unit in tertiary care medical centre in south-west Germany. STUDY DESIGN Prospective cohort study of individuals with and without cardiovascular disease at baseline. PATIENTS AND METHODS LURIC is an ongoing prospective study of currently > 3300 individuals in whom the cardiovascular and metabolic phenotypes CAD, MI, dyslipidaemia, hypertension, metabolic syndrome and diabetes mellitus have been defined or ruled out using standardised methodologies in all study participants. Inclusion criteria for LURIC were: German ancestry (limitation of genetic heterogeneity) clinical stability (except for acute coronary syndromes [ACSs]) availability of a coronary angiogram (this inclusion criterium was waived for family members provided that they met all other inclusion and exclusion criteria) Exclusion criteria were: any acute illness other than ACSs any chronic disease where non-cardiac disease predominated a history of malignancy within the past five years. Exclusion criteria were pre-specified in order to minimise the impact of concomitant non-cardiovascular disease on intermediate biochemical phenotypes or on clinical prognosis (limitation of clinical heterogeneity). A standardised personal and family history questionnaire and an extensive laboratory work-up (including glucose tolerance testing in non-diabetics and objective assessment of smoking exposure by determination of cotinine plasma levels) was obtained from all individuals after informed consent. A total of 115 ml of fasting venous blood was sampled for the determination of a pre-specified wide range of intermediate biochemical phenotypes in serum, plasma or whole blood, for leukocyte DNA extraction and immortalisation of B-lymphocytes. Biochemical phenotypes measured included markers of endothelial dysfunction, inflammation, oxidative status, coagulation, lipid metabolism and flow cytometric surface receptor expression of lympho-, mono- and thrombocytes. In addition, multiple aliquots of blood samples were stored for future analyses. RESULTS A total of 3500 LURIC baseline measurements were performed in 3316 individuals between July 1997 and January 2000. The baseline examination was repeated within a median of 35 days in 5% of study participants (n = 166, including a third examination in 18 after a median of 69 days) for pharmacogenomic assessment of lipid-lowering therapy and for quality control purposes. A five-year follow-up on major clinical events (death, any cardiovascular event including MI, stroke and revascularisation, malignancy and any hospitalisation) is ongoing. The clinical phenotypes prevalent at baseline in the cohort of 2309 men (70%) with a mean age of 62 +/- 11 years and 1007 women (30%), mean age 65 +/- 10 years, were angiographically-documented CAD in 2567 (79%), MI in 1368 (41%), dyslipidaemia in 2050 (62%) with hypercholesterolaemia > or = 240 mg/dl (27%), hypertriglyceridaemia > or = 150 mg/dl (44%) and HDL-cholesterol < or = 35 mg/dl (38%) in individuals not treated with lipid-lowering agents, systemic hypertension in 1921 (58%), metabolic syndrome in 1591 (48%), Type 2 diabetes in 1063 (32%) and obesity defined by body mass index > or = 30 kg/m2 in 770 (23%). Control patients in whom CAD had been ruled out angiographically were five years younger than those with CAD (59 +/- 12 and 64 +/- 10 years, respectively; p < 0.001), twice as often females (48% compared to 25% females in the CAD group, p < 0.001) and had significantly less cardiovascular risk factors than individuals with CAD. The prevalence of specific cardiovascular risk subsets in LURIC, such as the elderly (> or = 75 years), was 375 (11%), while 213 (6%) were young adults (< 45 years) and 904 (27%) were postmenopausal women (90% of all females). A low risk status (< or = 1 out of the four traditional risk factors: dyslipidaemia, smoking, hypertension and diabetes mellitus) was identified in 314 (9%) individuals of the entire cohort (5% in CAD and 26% in controls, p < 0.001) and 97 (3%) carried none of the four risk factors (1% in CAD and 9% in controls, p < 0.001). (ABSTRACT TRUNCATED)

EuroCMR (European Cardiovascular Magnetic Resonance) Registry: Results of the German Pilot Phase

OBJECTIVES During its German pilot phase, the EuroCMR (European Cardiovascular Magnetic Resonance) registry sought to evaluate indications, image quality, safety, and impact on patient management of routine CMR. BACKGROUND CMR has a broad range of applications and is increasingly used in clinical practice. METHODS This was a multicenter registry with consecutive enrollment of patients in 20 German centers. RESULTS A total of 11,040 consecutive patients were enrolled. Eighty-eight percent of patients received gadolinium-based contrast agents. Twenty-one percent underwent adenosine perfusion, and 11% high-dose dobutamine-stress CMR. The most important indications were workup of myocarditis/cardiomyopathies (32%), risk stratification in suspected coronary artery disease/ischemia (31%), as well as assessment of viability (15%). Image quality was good in 90.1%, moderate in 8.1%, and inadequate in 1.8% of cases. Severe complications occurred in 0.05%, and were all associated with stress testing. No patient died during or due to CMR. In nearly two-thirds of patients, CMR findings impacted patient management. Importantly, in 16% of cases the final diagnosis based on CMR was different from the diagnosis before CMR, leading to a complete change in management. In more than 86% of cases, CMR was capable of satisfying all imaging needs so that no further imaging was required. CONCLUSIONS CMR is frequently performed in clinical practice in many participating centers. The most important indications are workup of myocarditis/cardiomyopathies, risk stratification in suspected coronary artery disease/ischemia, and assessment of viability. CMR imaging as used in the centers of the pilot registry is a safe procedure, has diagnostic image quality in 98% of cases, and its results have strong impact on patient management.

Ventricular arrhythmias in idiopathic dilated cardiomyopathy.

Twenty four hour ambulatory electrocardiograms were recorded in 60 patients with idiopathic dilated cardiomyopathy. The diagnosis was based on clinical, laboratory, and cardiac catheterisation findings. All patients had a left ventricular ejection fraction less than 0.55; in 39 it was less than 0.40. Ventricular extrasystoles were evident in all patients: they were rare in 11 (18%), moderately frequent in 24 (40%), and frequent in 25 (42%). Multiform extrasystoles were recorded in 57 patients (95%), paired ventricular extrasystoles in 47 (78%), and non-sustained ventricular tachycardias consisting of three to 19 beats in 25 (42%) of the 60 patients studied. Eight patients had more than five episodes of ventricular tachycardia a day. Patients with atrial fibrillation had the same frequency and grade of ventricular arrhythmias as those with sinus rhythm. Patients with infrequent and frequent ventricular extrasystoles could not be differentiated on the basis of the clinical or haemodynamic findings. The mean values of NYHA functional class, cardiac index, left ventricular end diastolic pressure, and ejection fraction were, however, significantly different in patients with and without ventricular tachycardia. During follow up of 12 +/- 5 months seven patients died; all seven had an ejection fraction less than 0.40. In four patients who died of congestive heart failure, but in only one of the three patients who died a sudden cardiac death, ventricular tachycardia was recorded during ambulatory monitoring. High grade ventricular arrhythmias are often seen in patients with idiopathic dilated cardiomyopathy; patients with ventricular tachycardia have more impairment of left ventricular function than patients without ventricular tachycardia; and ambulatory monitoring may be of little help in identifying patients at increased risk of sudden cardiac death.

MitraClip therapy in daily clinical practice: initial results from the German transcatheter mitral valve interventions (TRAMI) registry

A substantial percentage of patients with mitral regurgitation (MR) in need of mitral valve repair are currently considered not suitable for conventional surgery. In Germany, the largest cohort of patients studied to date has been treated using a percutaneous, catheter‐based approach. We report the acute outcomes of patients enrolled in the investigator‐initiated German transcatheter mitral valve interventions (TRAMI) registry.

Risk of thromboembolic events in patients with atrial flutter

Based on multiple studies, clear, guided anticoagulation therapy is recommended for patients with atrial fibrillation. The value of anticoagulation therapy in patients with atrial flutter, however, is less well established. Little is known about the incidence of thromboembolism in patients with atrial flutter. We evaluated the risk of thromboembolism in 191 consecutive unselected patients referred for treatment of atrial flutter. A history of embolic events was noted in 11 patients. Acute embolism (<48 hours) occurred in 4 patients (3 after direct current cardioversion, 1 after catheter ablation). During follow-up of 26+/-18 months, 9 patients experienced thromboembolic events. During the follow-up, the overall embolic event rate (including acute embolism and thromboembolic events during follow-up) was 7 % in this patient population. Risk indicators for an embolic event in an univariate analysis were organic heart disease (p = 0.037), depressed left ventricular function (p = 0.02), history of systemic hypertension (p = 0.004), and diabetes mellitus (p = 0.0038). Using multivariate analysis, a history of hypertension was the only independent predictor for elevated embolic risk in this patient population (odds ratio = 6.5; 95% confidence intervals 1.5 to 45). Thus, the thromboembolic risk is higher than previously recognized for patients with atrial flutter. Anticoagulation therapy may decrease this risk.