Juliane Herm

Neuropsychological effects of MRI-detected brain lesions after left atrial catheter ablation for atrial fibrillation: long-term results of the MACPAF study.

Background— MRI-detected brain lesions are common after left atrial catheter ablation for symptomatic atrial fibrillation. The clinical relevance of these acute ischemic lesions is not fully understood, but ablation-related cerebral injury could contribute to cognitive dysfunction. Methods and Results— In the prospective Mesh Ablator versus Cryoballoon Pulmonary Vein Ablation of Symptomatic Paroxysmal Atrial Fibrillation (MACPAF) study, serial 3-T brain MRIs and neuropsychological assessment were performed to analyze the rate of ablation-related brain lesions and their effect on cognitive function. Thirty-seven patients with paroxysmal atrial fibrillation (median age, 63.0 [interquartile range, 57–68] years; 41% female; median CHA2DS2VASc score 2 [interquartile range, 1–3]) underwent 41 ablation procedures according to study criteria. None of these patients had overt neurological deficits after ablation. High-resolution diffusion-weighted imaging, performed within 48 hours after ablation, showed that new brain lesions (range, 1–17) were present in 16 (43.2%) patients after 18 (43.9%) left atrial catheter ablation procedures. Follow-up MRI at 6 months (median, 6.5; interquartile range, 6–7) revealed that 7 (12.5%) of the 56 total acute brain lesions after ablation formed a persistent glial scar in 5 (31.3%) patients. Large diffusion-weighted imaging lesions and a corresponding fluid-attenuated inversion recovery lesion 48 hours after ablation predicted lesion persistence on 6-month follow-up. Neither persistent brain lesions nor the ablation procedure itself had a significant effect on attention or executive functions, short-term memory, or verbal and nonverbal learning after 6 months. Conclusions— Ablation-related acute ischemic brain lesions persist to some extent but do not cause cognitive impairment 6 months after the ablation procedure. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01061931.

Should transesophageal echocardiography be performed in acute stroke patients with atrial fibrillation

The diagnostic need for echocardiography in acute stroke patients with documented atrial fibrillation (AF) is controversial because the index stroke per se is an indication for therapeutic anticoagulation according to guidelines. We retrospectively analyzed medical records of 2390 stroke patients consecutively admitted over a 2-year period to three different stroke units at university hospitals in Berlin, Germany. AF was diagnosed in 21.2% (n=506) of 2185 patients with acute ischemic stroke or transient ischemic attack. Overall, 36.6% (n=185) of all AF patients underwent transesophageal echocardiography (TEE) or transthoracic echocardiography within days of hospital admission. According to multivariate analysis, age and in-hospital conventions determined the diagnostic use of TEE in stroke patients with known AF, while the existing cardiovascular risk profile had no impact. Major cardiac sources of embolism were identified by echocardiography in 9.7% (n=18) of all AF patients with acute stroke, including non-AF-related sources of embolism in 3.8% (n=7). However, echocardiographic findings did not result in any therapeutic intervention other than immediate anticoagulation. Furthermore, echocardiographic findings had no impact on the prescription of anticoagulants at hospital discharge or long-term survival. Taken together, our data indicate that diagnostic echocardiography offers only a little additional information and does not impact clinical management and outcome in acute stroke patients with known AF.

Marathon running increases circulating endothelial- and thrombocyte-derived microparticles

Background Acute vascular effects of high intensity physical activity are incompletely characterized. Circulating microparticles are cellular markers for vascular activation and damage. Methods Microparticles were analysed in 99 marathon runners (49 ± 6 years, 22% female) of the prospective Berlin Beat of Running study. Blood samples were taken within three days before, immediately after and within two days after the marathon run. Endothelial-derived microparticles were labelled with CD144, CD31 and CD62E, platelet-derived microparticles with CD62P and CD42b, leukocyte-derived microparticles with CD45 and monocyte-derived microparticles with CD14. Results Marathon running induced leukocytosis (5.9 ± 0.1 to 14.8 ± 0.3 109/l, p < 0.0001) and increased platelet counts (239 ± 4.6 to 281 ± 5.9 109/l, p < 0.0001) immediately after the marathon. Blood monocytes increased and lymphocytes decreased after the run (p < 0.0001). Endothelial-derived microparticles were acutely increased (p = 0.008) due to a 23% increase of apoptotic endothelial-derived microparticles (p = 0.007) and returned to baseline within two days after the marathon. Thrombocyte-derived microparticles acutely increased by 38% accompanied by an increase in activated and apoptotic thrombocyte-derived microparticles (p ≤ 0.0001) each. Both monocyte- and leukocyte-derived microparticles were decreased immediately after marathon run (p < 0.0001) and remained below baseline until day 2. Troponin T increased from 12 to 32 ng/l (p < 0.0001) immediately after the run and returned to baseline after two days. Conclusion Circulating apoptotic endothelial- and thrombocyte-derived microparticles increased after marathon running consistent with an acute pro-thrombotic and pro-inflammatory state. Exercise-induced vascular damage reflected by microparticles could indicate potential mechanisms of post-exertional cardiovascular complications. Further studies are warranted to investigate microparticles as markers to identify individuals prone to such complications.

Feasibility and Diagnostic Value of Cardiovascular Magnetic Resonance Imaging After Acute Ischemic Stroke of Undetermined Origin

Background and Purpose— Etiology of acute ischemic stroke remains undetermined (cryptogenic) in about 25% of patients after state-of-the-art diagnostic work-up. Methods— One-hundred and three patients with magnetic resonance imaging (MRI)–proven acute ischemic stroke of undetermined origin were prospectively enrolled and underwent 3-T cardiac MRI and magnetic resonance angiography of the aortic arch in addition to state-of-the-art diagnostic work-up, including transesophageal echocardiography (TEE). We analyzed the feasibility, diagnostic accuracy, and added value of cardiovascular MRI (cvMRI) compared with TEE for detecting sources of stroke. Results— Overall, 102 (99.0%) ischemic stroke patients (median 63 years [interquartile range, 53–72], 24% female, median NIHSS (National Institutes of Health Stroke Scale) score on admission 2 [interquartile range, 1–4]) underwent cvMRI and TEE in hospital; 89 (86.4%) patients completed the cvMRI examination. In 93 cryptogenic stroke patients, a high-risk embolic source was found in 9 (8.7%) patients by cvMRI and in 11 (11.8%) patients by echocardiography, respectively. cvMRI and echocardiography findings were consistent in 80 (86.0%) patients, resulting in a degree of agreement of &kgr;=0.24. In 82 patients with cryptogenic stroke according to routine work-up, including TEE, cvMRI identified stroke etiology in additional 5 (6.1%) patients. Late gadolinium enhancement consistent with previous myocardial infarction was found in 13 (14.6%) out of 89 stroke patients completing cvMRI. Only 2 of these 13 patients had known coronary artery disease. Conclusions— Our study demonstrated that cvMRI was feasible in the vast majority of included patients with acute ischemic stroke. The diagnostic information of cvMRI seems to be complementary to TEE but is not replacing echocardiography after acute ischemic stroke. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01917955.

Rate of cardiac arrhythmias and silent brain lesions in experienced marathon runners: rationale, design and baseline data of the Berlin Beat of Running study

BackgroundRegular exercise is beneficial for cardiovascular health but a recent meta-analysis indicated a relationship between extensive endurance sport and a higher risk of atrial fibrillation, an independent risk factor for stroke. However, data on the frequency of cardiac arrhythmias or (clinically silent) brain lesions during and after marathon running are missing.Methods/ DesignIn the prospective observational “Berlin Beat of Running” study experienced endurance athletes underwent clinical examination (CE), 3 Tesla brain magnetic resonance imaging (MRI), carotid ultrasound imaging (CUI) and serial blood sampling (BS) within 2-3 days prior (CE, MRI, CUI, BS), directly after (CE, BS) and within 2 days after (CE, MRI, BS) the 38th BMW BERLIN-MARATHON 2011. All participants wore a portable electrocardiogram (ECG)-recorder throughout the 4 to 5 days baseline study period. Participants with pathological MRI findings after the marathon, troponin elevations or detected cardiac arrhythmias will be asked to undergo cardiac MRI to rule out structural abnormalities. A follow-up is scheduled after one year.ResultsHere we report the baseline data of the enrolled 110 athletes aged 36-61 years. Their mean age was 48.8 ± 6.0 years, 24.5% were female, 8.2% had hypertension and 2.7% had hyperlipidaemia. Participants have attended a mean of 7.5 ± 6.6 marathon races within the last 5 years and a mean of 16 ± 36 marathon races in total. Their weekly running distance prior to the 38th BMW BERLIN-MARATHON was 65 ± 17 km. Finally, 108 (98.2%) Berlin Beat-Study participants successfully completed the 38th BMW BERLIN-MARATHON 2011.DiscussionFindings from the “Berlin Beats of Running” study will help to balance the benefits and risks of extensive endurance sport. ECG-recording during the marathon might contribute to identify athletes at risk for cardiovascular events. MRI results will give new insights into the link between physical stress and brain damage.Trial registrationclinicaltrials.gov NCT01428778

Frequency of exercise-induced ST-T-segment deviations and cardiac arrhythmias in recreational endurance athletes during a marathon race: results of the prospective observational Berlin Beat of Running study

Objectives While regular physical exercise has many health benefits, strenuous physical exercise may have a negative impact on cardiac function. The ‘Berlin Beat of Running’ study focused on feasibility and diagnostic value of continuous ECG monitoring in recreational endurance athletes during a marathon race. We hypothesised that cardiac arrhythmias and especially atrial fibrillation are frequently found in a cohort of recreational endurance athletes. The main secondary hypothesis was that pathological laboratory findings in these athletes are (in part) associated with cardiac arrhythmias. Design Prospective observational cohort study including healthy volunteers. Setting and participants One hundred and nine experienced marathon runners wore a portable ECG recorder during a marathon race in Berlin, Germany. Athletes underwent blood tests 2–3 days prior, directly after and 1–2 days after the race. Results Overall, 108 athletes (median 48 years (IQR 45–53), 24% women) completed the marathon in 249±43 min. Blinded ECG analysis revealed abnormal findings during the marathon in 18 (16.8%) athletes. Ten (9.3%) athletes had at least one episode of non-sustained ventricular tachycardia, one of whom had atrial fibrillation; eight (7.5%) individuals showed transient ST-T-segment deviations. Abnormal ECG findings were associated with advanced age (OR 1.11 per year, 95% CI 1.01 to 1.23), while sex and cardiovascular risk profile had no impact. Directly after the race, high-sensitive troponin T was elevated in 18 (16.7%) athletes and associated with ST-T-segment deviation (OR 9.9, 95% CI 1.9 to 51.5), while age, sex and cardiovascular risk profile had no impact. Conclusions ECG monitoring during a marathon is feasible. Abnormal ECG findings were present in every sixth athlete. Exercise-induced transient ST-T-segment deviations were associated with elevated high-sensitive troponin T (hsTnT) values. Trial registration ClinicalTrials.gov NCT01428778; Results.

Loop Recorder Detected High Rate of Atrial Fibrillation Recurrence after a Single Balloon- or Basket-Based Ablation of Paroxysmal Atrial Fibrillation: Results of the MACPAF Study

Purpose Pulmonary vein isolation (PVI) is an established approach to treat symptomatic non-permanent atrial fibrillation (AF). Detecting AF recurrence after PVI is important, if discontinuation of oral anticoagulation after ablation is considered. Methods Patients with symptomatic paroxysmal AF were enrolled in the prospective randomized mesh ablator vs. cryoballoon pulmonary vein (PV) ablation of symptomatic paroxysmal AF study, comparing efficacy and safety of the HD Mesh Ablator® (C.R. Bard, Lowell, MA, USA) and the Arctic Front® (Medtronic, Minneapolis, MN, USA) catheter. Rhythm status post-PVI was closely monitored for 1 year using the implantable loop recorder (ILR) Reveal XT® (Medtronic Minneapolis, MN, USA). Results The study was terminated after the first interim analysis due to the inability of the HD Mesh Ablator® to achieve the predefined primary study endpoint, an exit block of all PVs. After a 90-day blanking period, 23 (62.2%) out of 37 study patients (median 63.0 years; 41% females) had at least one episode of AF. AF recurrence was associated with AF episodes during the blanking period {hazard ratios (HR) 5.10 [95% confidence interval (CI) 1.21–21.4]; p = 0.038}, and a common left-sided PV ostium [HR 4.17 (95%CI 1.48–11.8); p = 0.039] but not with catheter type, age, gender, cardiovascular risk profile, or left atrial volume. There was a trend toward AF recurrence in patients without complete PVI of all PV (p = 0.095). Overall, 337 (59.4%) out of 566 ILR-detected episodes represented AF. Comparing patients with AF recurrence to those without, there was no difference in cognitive performance 6 months post-ablation. Conclusion Using an ILR, in more than 60% of all patients with paroxysmal AF, a recurrence of AF was detected within 12 months after ablation. In patients with a common PV ostium, the first generation balloon-based catheter is obviously less effective. Clinical trials http://Clinicaltrials.gov NCT01061931.

A Prothrombotic Score Based on Genetic Polymorphisms of the Hemostatic System Differs in Patients with Ischemic Stroke, Myocardial Infarction, or Peripheral Arterial Occlusive Disease

Background While twin studies indicate a genetic component in arterial thrombosis such as ischemic stroke, myocardial infarction (MI), or peripheral arterial occlusive disease (PAOD), the clinical relevance of hemostatic polymorphisms in arterial thrombosis is a matter of debate. Methods We analyzed the prevalence of 13 hemostatic polymorphisms [PAI-1, PLAT, F5 (including factor V Leiden and HR2 haplotype), F2, F7, F13A, FGB, TFPI, THBD, MTHFR, ACE, and ITGA2] in patients referred to a tertiary referral center. A “prothrombotic score” was calculated by dividing the number of risk-increasing polymorphisms for thrombosis minus the number of risk-lowering polymorphisms (F7 and F13A) by the number of polymorphisms tested. Results Datasets of 144 patients with prior ischemic stroke (mean age 44 ± 13 years; 65% female) were compared to 62 patients with MI or PAOD (mean age 54 ± 14 years; 47% female). The prothrombotic score was lower in MI and PAOD patients compared to stroke patients [odds ratios 2.7 (95% confidence intervals 1.1–6.2)]. Frequencies of individual polymorphisms did not differ between both groups. Conclusion Patients with MI or PAOD had a lower burden of prothrombotic mutations compared to patients with prior stroke, indicating that a prothrombotic state might play a different role in distinct forms of arterial thrombosis.

Neuropsychological Effects of MRI-Detected Brain Lesions After Left Atrial Catheter Ablation for Atrial FibrillationClinical Perspective: Long-Term Results of the MACPAF Study

Background— MRI-detected brain lesions are common after left atrial catheter ablation for symptomatic atrial fibrillation. The clinical relevance of these acute ischemic lesions is not fully understood, but ablation-related cerebral injury could contribute to cognitive dysfunction. Methods and Results— In the prospective Mesh Ablator versus Cryoballoon Pulmonary Vein Ablation of Symptomatic Paroxysmal Atrial Fibrillation (MACPAF) study, serial 3-T brain MRIs and neuropsychological assessment were performed to analyze the rate of ablation-related brain lesions and their effect on cognitive function. Thirty-seven patients with paroxysmal atrial fibrillation (median age, 63.0 [interquartile range, 57–68] years; 41% female; median CHA2DS2VASc score 2 [interquartile range, 1–3]) underwent 41 ablation procedures according to study criteria. None of these patients had overt neurological deficits after ablation. High-resolution diffusion-weighted imaging, performed within 48 hours after ablation, showed that new brain lesions (range, 1–17) were present in 16 (43.2%) patients after 18 (43.9%) left atrial catheter ablation procedures. Follow-up MRI at 6 months (median, 6.5; interquartile range, 6–7) revealed that 7 (12.5%) of the 56 total acute brain lesions after ablation formed a persistent glial scar in 5 (31.3%) patients. Large diffusion-weighted imaging lesions and a corresponding fluid-attenuated inversion recovery lesion 48 hours after ablation predicted lesion persistence on 6-month follow-up. Neither persistent brain lesions nor the ablation procedure itself had a significant effect on attention or executive functions, short-term memory, or verbal and nonverbal learning after 6 months. Conclusions— Ablation-related acute ischemic brain lesions persist to some extent but do not cause cognitive impairment 6 months after the ablation procedure. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01061931.

Neuropsychological Effects of MRI-Detected Brain Lesions After Left Atrial Catheter Ablation for Atrial FibrillationClinical Perspective

Background— MRI-detected brain lesions are common after left atrial catheter ablation for symptomatic atrial fibrillation. The clinical relevance of these acute ischemic lesions is not fully understood, but ablation-related cerebral injury could contribute to cognitive dysfunction. Methods and Results— In the prospective Mesh Ablator versus Cryoballoon Pulmonary Vein Ablation of Symptomatic Paroxysmal Atrial Fibrillation (MACPAF) study, serial 3-T brain MRIs and neuropsychological assessment were performed to analyze the rate of ablation-related brain lesions and their effect on cognitive function. Thirty-seven patients with paroxysmal atrial fibrillation (median age, 63.0 [interquartile range, 57–68] years; 41% female; median CHA2DS2VASc score 2 [interquartile range, 1–3]) underwent 41 ablation procedures according to study criteria. None of these patients had overt neurological deficits after ablation. High-resolution diffusion-weighted imaging, performed within 48 hours after ablation, showed that new brain lesions (range, 1–17) were present in 16 (43.2%) patients after 18 (43.9%) left atrial catheter ablation procedures. Follow-up MRI at 6 months (median, 6.5; interquartile range, 6–7) revealed that 7 (12.5%) of the 56 total acute brain lesions after ablation formed a persistent glial scar in 5 (31.3%) patients. Large diffusion-weighted imaging lesions and a corresponding fluid-attenuated inversion recovery lesion 48 hours after ablation predicted lesion persistence on 6-month follow-up. Neither persistent brain lesions nor the ablation procedure itself had a significant effect on attention or executive functions, short-term memory, or verbal and nonverbal learning after 6 months. Conclusions— Ablation-related acute ischemic brain lesions persist to some extent but do not cause cognitive impairment 6 months after the ablation procedure. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01061931.