Andras Treszl

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.

Impact of Complete Versus Incomplete Circumferential Lines Around the Pulmonary Veins During Catheter Ablation of Paroxysmal Atrial Fibrillation: Results From the Gap-Atrial Fibrillation-German Atrial Fibrillation Competence Network 1 Trial.

Background—Ablation of atrial fibrillation (AF) is an established treatment option for symptomatic patients. It is not known whether complete pulmonary vein isolation (PVI) is superior to incomplete PVI with regard to the patients’ clinical outcome. Methods and Results—Patients with drug-refractory, symptomatic paroxysmal AF were randomly assigned to either incomplete (group A) or complete PVI (group B). In group A, a persistent gap was intentionally left within the circumferential ablation line, whereas in group B, complete PVI without any gaps was intended. At 3 months, all patients underwent invasive reevaluation to assess the rate of persistent PVI. Clinical follow-up was based on daily 30-s transtelephonic ECG transmissions. Primary study end point was the time to first recurrence of (symptomatic or asymptomatic) AF. A total of 233 patients were enrolled (116 in group A and 117 in group B). AF recurrence within 3 months was observed in a total of 161 patients (136 [84.5%] with symptomatic and 25 [15.5%] with asymptomatic AF); AF recurred in 62.2% of group B patients and 79.2% of group A patients (P<0.001), for a difference in favor of complete PVI of 17.1% (95% confidence interval, 5.3%–28.9%). Invasive restudy in 103 group A patients and 93 group B patients revealed conduction gaps in 92 (89.3%) and 65 (69.9%) patients, respectively. Conclusions—This study proves the superiority of complete PVI over incomplete PVI with respect to AF recurrence within 3 months. However, the rate of electric reconduction 3 months after PVI is high in patients with initially isolated PVs. Clinical Trial Registration—URL: http://clinicaltrials.gov; Unique identifier: NCT00293943.

Acupuncture in Patients With Seasonal Allergic Rhinitis: A Randomized Trial

UNLABELLED Chinese translation BACKGROUND Acupuncture is frequently used to treat seasonal allergic rhinitis (SAR) despite limited scientific evidence. OBJECTIVE To evaluate the effects of acupuncture in patients with SAR. DESIGN Randomized, controlled multicenter trial. (ClinicalTrials.gov: NCT00610584) SETTING 46 specialized physicians in 6 hospital clinics and 32 private outpatient clinics. PATIENTS 422 persons with SAR and IgE sensitization to birch and grass pollen. INTERVENTION Acupuncture plus rescue medication (RM) (cetirizine) (n = 212), sham acupuncture plus RM (n = 102), or RM alone (n = 108). Twelve treatments were provided over 8 weeks in the first year. MEASUREMENTS Changes in the Rhinitis Quality of Life Questionnaire (RQLQ) overall score and the RM score (RMS) from baseline to weeks 7 and 8 and week 16 in the first year and week 8 in the second year after randomization, with predefined noninferiority margins of -0.5 point (RQLQ) and -1.5 points (RMS). RESULTS Compared with sham acupuncture and with RM, acupuncture was associated with improvement in RQLQ score (sham vs. acupuncture mean difference, 0.5 point [97.5% CI, 0.2 to 0.8 point; P < 0.001]; RM vs. acupuncture mean difference, 0.7 point [97.5% CI, 0.4 to 1.0 point; P < 0.001]) and RMS (sham vs. acupuncture mean difference, 1.1 points [97.5% CI, 0.4 to 1.9 points; P < 0.001]; RM vs. acupuncture mean difference, 1.5 points [97.5% CI, 0.8 to 2.2 points; P < 0.001]). There were no differences after 16 weeks in the first year. After the 8-week follow-up phase in the second year, small improvements favoring real acupuncture over the sham procedure were noted (RQLQ mean difference, 0.3 point [95% CI, 0.03 to 0.6 point; P = 0.032]; RMS mean difference, 1.0 point [95% CI, 0.2 to 1.9 points; P = 0.018]). LIMITATION The study was not powered to detect rare adverse events, and the RQLQ and RMS values were low at baseline. CONCLUSION Acupuncture led to statistically significant improvements in disease-specific quality of life and antihistamine use measures after 8 weeks of treatment compared with sham acupuncture and with RM alone, but the improvements may not be clinically significant.

Endoscopic versus histological characterisation of polyps during screening colonoscopy

Background As screening colonoscopy becomes more widespread, the costs for histopathological assessment of resected polyps are rising correspondingly. Reference centres have published highly accurate results for endoscopic polyp classification. Therefore, it has been proposed that, for smaller polyps, the differential diagnosis that guides follow-up recommendations could be based on endoscopy alone. Objective The aim was to prospectively assess whether the high accuracy for endoscopic polyp diagnosis as reported by reference centres can be reproduced in routine screening colonoscopy. Design Ten experienced private practice endoscopists had initial training in pit patterns. Then they assessed all polyps detected during 1069 screening colonoscopies. Patients (46% men; mean age 63 years) were randomly assigned to colonoscopy with conventional or latest generation HDTV instruments. The main outcome measure was diagnostic accuracy of in vivo polyp assessment (adenomatous vs hyperplastic). Secondary outcome measures were differences between endoscopes and reliability of image-based follow-up recommendations; a blinded post hoc analysis of polyp photographs was also performed. Results 675 polyps were assessed (461 adenomatous, 214 hyperplastic). Accuracy, sensitivity and specificity of in vivo diagnoses were 76.6%, 78.1% and 73.4%; size of adenomas and endoscope withdrawal time significantly influenced accuracy. Image-based recommendations for post-polypectomy surveillance were correct in only 69.5% of cases. Post hoc analysis of polyp photographs did not improve accuracy. Conclusions In everyday practice, endoscopic classification of polyp type is not accurate enough to abandon histopathological assessment and use of latest generation colonoscopes does not improve this. Image-based surveillance recommendations after polypectomy would consequently not meet guideline requirements. TrialRegNo NCT01297712.

Drug-coated balloon angioplasty after directional atherectomy improves outcome in restenotic femoropopliteal arteries

BACKGROUND Restenosis remains an unresolved problem despite different treatment modalities and new stent technology in femoropopliteal arteries. No standard therapy has proven to provide acceptable outcome data for this entity. Directional atherectomy alone did not result in satisfactory long-term patency rates. The outcome might be improved in conjunction with drug-coated balloon angioplasty. METHODS In this retrospective study, restenotic lesions of the femoropopliteal arteries were treated with directed atherectomy in 89 lesions of consecutive patients (58% male; mean age, 69 ± 11 years). All patients received adjunctive treatment with conventional balloon percutaneous angioplasty (PTA; n = 60) or drug-coated balloon angioplasty (DCB; n = 29). RESULTS Lesion location was in the stent (DCB [n = 27] vs PTA [n = 36]) and in native restenotic vessels (DCB [n = 2] vs PTA [n = 25]). The 1-year Kaplan-Meier freedom from restenosis estimates (95% confidence intervals) in the DCB and PTA groups were 84.7% (70.9%-98.5%) and 43.8% (30.5%-57.1%), respectively. In a multivariable Cox model for restenosis, DCB treatment had a hazard ratio (95% confidence interval) of 0.28 (0.12-0.66; P = .0036) compared with the PTA group. In the multivariable model for procedural success, the effect of treatment did not differ between PTA and DCB (P = .134). CONCLUSIONS The combination of directed atherectomy with adjunctive DCB is associated with a better event-free survival at 12 months of follow-up compared with PTA after directed atherectomy.

Altered intrahemispheric structural connectivity in Gilles de la Tourette syndrome

Gilles de la Tourette syndrome (GTS) is a common developmental neuropsychiatric disorder characterized by tics and frequent psychiatric comorbidities, often causing significant disability. Tic generation has been linked to disturbed networks of brain areas involved in planning, controlling and execution of actions, particularly structural and functional disorders in the striatum and cortico–striato–thalamo–cortical loops. We therefore applied structural diffusion tensor imaging (DTI) to characterize changes in intrahemispheric white matter connectivity in cortico-subcortical circuits engaged in motor control in 15 GTS patients without psychiatric comorbidities. White matter connectivity was analyzed by probabilistic fiber tractography between 12 predefined cortical and subcortical regions of interest. Connectivity values were combined with measures of clinical severity rated by the Yale Global Tic Severity Scale (YGTSS). GTS patients showed widespread structural connectivity deficits. Lower connectivity values were found specifically in tracts connecting the supplementary motor areas (SMA) with basal ganglia (pre-SMA–putamen, SMA–putamen) and in frontal cortico-cortical circuits. There was an overall trend towards negative correlations between structural connectivity in these tracts and YGTSS scores. Structural connectivity of frontal brain networks involved in planning, controlling and executing actions is reduced in adult GTS patients which is associated with tic severity. These findings are in line with the concept of GTS as a neurodevelopmental disorder of brain immaturity.

Quantitative measurements of relative fluid-attenuated inversion recovery (FLAIR) signal intensities in acute stroke for the prediction of time from symptom onset

In acute stroke magnetic resonance imaging, a ‘mismatch’ between visibility of an ischemic lesion on diffusion-weighted imaging (DWI) and missing corresponding parenchymal hyperintensities on fluid-attenuated inversion recovery (FLAIR) data sets was shown to identify patients with time from symptom onset ≤4.5 hours with high specificity. However, moderate sensitivity and suboptimal interpreter agreement are limitations of a visual rating of FLAIR lesion visibility. We tested refined image analysis methods in patients included in the previously published PREFLAIR study using refined visual analysis and quantitative measurements of relative FLAIR signal intensity (rSI) from a three-dimensional, segmented stroke lesion volume. A total of 399 patients were included. The rSI of FLAIR lesions showed a moderate correlation with time from symptom onset (r = 0.382, P < 0.001). A FLAIR rSI threshold of <1.0721 predicted symptom onset ≤4.5 hours with slightly increased specificity (0.85 versus 0.78) but also slightly decreased sensitivity (0.47 versus 0.58) as compared with visual analysis. Refined visual analysis differentiating between ‘subtle’ and ‘obvious’ FLAIR hyperintensities and classification and regression tree algorithms combining information from visual and quantitative analysis also did not improve diagnostic accuracy. Our results raise doubts whether the prediction of stroke onset time by visual image judgment can be improved by quantitative rSI measurements.

Effect of cardiac rehabilitation on functional and emotional status in patients after transcatheter aortic-valve implantation

Background Transcatheter aortic-valve implantation (TAVI) is an established alternative therapy in patients with severe aortic stenosis and a high surgical risk. Despite a rapid growth in its use, very few data exist about the efficacy of cardiac rehabilitation (CR) in these patients. We assessed the hypothesis that patients after TAVI benefit from CR, compared to patients after surgical aortic-valve replacement (sAVR). Methods From September 2009 to August 2011, 442 consecutive patients after TAVI (n = 76) or sAVR (n = 366) were referred to a 3-week CR. Data regarding patient characteristics as well as changes of functional (6-min walk test. 6-MWT), bicycle exercise test), and emotional status (Hospital Anxiety and Depression Scale) were retrospectively evaluated and compared between groups after propensity score adjustment. Results Patients after TAVI were significantly older (p < 0.001), more female (p < 0.001), and had more often coronary artery disease (p = 0.027), renal failure (p = 0.012) and a pacemaker (p = 0.032). During CR, distance in 6-MWT (both groups p ≤ 0.001) and exercise capacity (sAVR p ≤ 0.001, TAVI p ≤ 0.05) significantly increased in both groups. Only patients after sAVR demonstrated a significant reduction in anxiety and depression (p ≤ 0.001). After propensity scores adjustment, changes were not significantly different between sAVR and TAVI, with the exception of 6-MWT (p = 0.004). Conclusions Patients after TAVI benefit from cardiac rehabilitation despite their older age and comorbidities. CR is a helpful tool to maintain independency for daily life activities and participation in socio-cultural life.

Selection effects may account for better outcomes of the German Disease Management Program for type 2 diabetes

BackgroundThe nationwide German disease management program (DMP) for type 2 diabetes was introduced in 2003. Meanwhile, results from evaluation studies were published, but possible baseline differences between DMP and usual-care patients have not been examined. The objective of our study was therefore to find out if patient characteristics as socio-demographic variables, cardiovascular risk profile or motivation for life style changes influence the chance of being enrolled in the German DMP for type 2 diabetes and may therefore account for outcome differences between DMP and usual-care patients.MethodsCase control study comparing DMP patients with usual-care patients at baseline and follow up; mean follow-up period of 36 ± 14 months. We used chart review data from 51 GP surgeries. Participants were 586 DMP and 250 usual-care patients with type 2 diabetes randomly selected by chart registry. Data were analysed by multivariate logistic and linear regression analyses. Significance levels were p ≤ 0.05.ResultsThere was a better chance for enrolment if patients a) had a lower risk status for diabetes complications, i.e. non-smoking (odds ratio of 1.97, 95% confidence interval of 1.11 to 3.48) and lower systolic blood pressure (1.79 for 120 mmHg vs. 160 mmHg, 1.15 to 2.81); b) had higher activity rates, i.e. were practicing blood glucose self-monitoring (1.67, 1.03 to 2.76) and had been prescribed a diabetes patient education before enrolment (2.32, 1.29 to 4.19) c) were treated with oral medication (2.17, 1.35 to 3.49) and d) had a higher GP-rated motivation for diabetes education (4.55 for high motivation vs. low motivation, 2.21 to 9.36).ConclusionsAt baseline, future DMP patients had a lower risk for diabetes complications, were treated more intensively and were more active and motivated in managing their disease than usual-care patients. This finding a) points to the problem that the German DMP may not reach the higher risk patients and b) selection bias may impair the assessment of differences in outcome quality between enrolled and usual-care patients. Suggestions for dealing with this bias in evaluation studies are being made.

Disparity in risk factor pattern in premature versus late-onset coronary artery disease: a survey of 15,381 patients

Background There are few data available regarding the specificity and modifiability of major cardiovascular (CV) risk factors in patients with premature versus (vs) late-onset coronary artery disease (CAD). This study was designed to analyze and compare these risk factors. Patients and methods Data from 15,381 consecutive patients (mean age, 62.3 ± 11.7 years; female, 33.8%) hospitalized with CAD were collected from a large-scale registry (Transparency Registry to Objectify Guideline-Oriented Risk Factor Management) and analyzed. The patients were divided into two groups, depending on age at inclusion: group 1 patients (n = 5725; mean age, 50.5 ± 7.2 years) were males aged < 55 years and females aged < 65 years; group 2 patients (n = 9656; mean age, 69.4 ± 7.4 years) were males aged > 55 years and females aged > 65 years and had a low-density lipoprotein cholesterol level of >100 mg/dL on admission to cardiac rehabilitation. Besides the conventional risk factors, lipoprotein(a) concentrations and glucose tolerance were measured facultatively. Univariate (chi-square test) and multivariate logistic regression models were used. Results Cigarette smoking (group 1 at 31.5% vs group 2 at 9.4%; P < 0.001), family history of CAD (group 1 at 43.6% vs group 2 at 26.5%; P < 0.001), and dyslipidemia (group 1 at 92.7% vs group 2 at 91.8%; P < 0.001) were dominant risk factors in the younger group. Arterial hypertension (group 1 at 71.4% vs group 2 at 87.0%; P < 0.001) and diabetes (group 1 at 23.5% vs group 2 at 30.1%; P < 0.001) were dominant risk factors in the older group. Impaired glucose tolerance and diabetes were less frequent in the younger group (Ptrend = 0.038), and identical lipoprotein(a) concentration levels of >30 mg/dL were found in both groups (8.0%; P = 0.810). Modification of lipid profile and blood pressure was more effective in the younger group (low-density lipoprotein cholesterol < 100 mg/dL: group 1 at 66.3% vs group 2 at 61.1%; systolic blood pressure < 140 mmHg: group 1 at 91.7% vs group 2 at 83.0%; P < 0.001). Conclusion CV risk factors differ markedly between premature and non-premature CAD. Cardiac rehabilitation provides an opportunity to reinforce secondary prevention after acute coronary syndrome.