REduction of THRomboembolic EVents during Ablation using the laserballoon: The RETHREVA registry.

INTRODUCTION: Cerebral events (CEs), including silent (SCEs), are a known complication of left atrial catheter ablation (LACA) in patients with atrial fibrillation. The aim of this prospective registry was to gain more information about CEs during laserballoon LACA and to reduce the risk of their occurrence. METHODS AND RESULTS: We enrolled 74 patients (age 61 ± 11 years; 74% male; CHA2 DS2 -VASc 1.9 ± 1.4). Cerebral MRI (1.5 Tesla) was performed to detect CEs. ASPItest identified aspirin-resistant patients (ARPs). All bleeding complications were recorded. Due to an initial high CE rate, we evolved our clinical procedure step-by-step arriving at an optimized protocol: -Group 1: heparin after single transseptal puncture (TP), activated clotting time (ACT) > 300 seconds (CE: 64.3%). -Group 2: heparin after double TP, ACT > 300 seconds; 2a without (CE: 45.5%, RRR: -29.2%) and 2b with additional intravenous aspirin (CE: 36.4%, RRR: -43.4%; excluding ARP: 30%, RRR: -53.3%). -Group 3: heparin before double TP, ACT > 350 seconds; 3a without (CE: 54.5%, RRR: -15.2%) and 3b with aspirin (CE: 18.5%, RRR: -71.2%; excluding ARP: 8.7%, RRR: -86.5%). Larger LA diameter > 44 mm (OR: 1.149, P  =  0.005) and no aspirin use (OR: 4.308, P  =  0.008) were CE risk factors in multivariate logistic regression. In those patients receiving aspirin, aspirin resistance (OR: 22.4, P  =  0.011) was an exceptionally strong risk factor. CONCLUSION: These data support the use of intravenous aspirin including monitoring of aspirin resistance in addition to ACT-guided heparin. An optimized protocol of heparin before TP, double TP, and intravenous aspirin in non-ARP resulted in a significantly lowered CE incidence and severity.

[Insertable Cardiac Monitor]. / Der "insertierbare" Herzmonitor.

Intermittent cardiac arrhythmias are sometimes difficult to register using conventional detection concepts. The implantable event recorders offer a unique opportunity to document short lasting or rare and even asymptomatic arrhythmias. This manuscript describes event recorder implantation in a step-by-step manner.

Novel correlations between the genotype and the phenotype of hypertrophic and dilated cardiomyopathy: results from the German Competence Network Heart Failure.

AIMS: Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) can both be due to mutations in the genes encoding ß-myosin heavy chain (MYH7) or cardiac myosin-binding protein C (MYBPC3). The aim of the present study was to determine the prevalence and spectrum of mutations in both genes in German HCM and DCM patients and to establish novel genotype-to-phenotype correlations. METHODS AND RESULTS: Coding exons and intron flanks of the two genes MYH7 and MYBPC3 of 236 patients with HCM and 652 patients with DCM were sequenced by conventional and array-based means. Clinical records were established following standard protocols. Mutations were detected in 41 and 11% of the patients with HCM and DCM, respectively. Differences were observed in the frequency of splice site and frame-shift mutations in the gene MYBPC3, which occurred more frequently (P< 0.02, P< 0.001, respectively) in HCM than in DCM, suggesting that cardiac myosin-binding protein C haploinsufficiency predisposes to hypertrophy rather than to dilation. Additional novel genotype-to-phenotype correlations were found in HCM, among these a link between MYBPC3 mutations and a particularly large thickness of the interventricular septum (P= 0.04 vs. carriers of a mutation in MYH7). Interestingly, this correlation and a link between MYH7 mutations and a higher degree of mitral valve regurgitation held true for both HCM and DCM, indicating that the gene affected by a mutation may determine the magnitude of structural and functional alterations in both HCM and DCM. CONCLUSION: A large clinical-genetic study has unravelled novel genotype-to-phenotype correlations in HCM and DCM which warrant future investigation of both the underlying mechanisms and the prognostic use.

Normal values for longitudinal function of the right ventricle in healthy women >70 years of age.

AIMS: The application of tricuspid annular plane systolic excursion (TAPSE) as an additional echocardiographic tool to analyse right ventricular (RV) systolic function has been recently established and two-dimensional-guided M-mode measurements of systolic long axis function of the RV are simple, repeatable, and highly reproducible. However, rare data are available on normal values. We aimed to analyse normal values in healthy women >70 years of age. METHODS AND RESULTS: In a cross-sectional survey, we investigated a cohort of randomly selected, non-hospitalized women >70 years of age. History of myocardial infarction, valvular heart disease, and diastolic dysfunction were exclusion criteria. In order to rule out left ventricular or RV dysfunction, a normal left ventricular ejection fraction and normal values of B-type natriuretic peptide (BNP) were necessary prior to study inclusion. A detailed echocardiographic examination was performed. A total of 80 participants were included (mean age 75 +/- 2.6 years). Mean left ventricular ejection fraction was 63.8 +/- 5.7%. Tissue Doppler derived mean E/E' ratio was 10 +/- 2.3. Mean right atrial diameter was 31.3 +/- 4.7 mm. Mean values for RV outflow tract and RV dimension were 27.3 +/- 3.6 and 28.8 +/- 3.7 mm, respectively. Mean TAPSE was 23.7 +/- 3.5 mm. Mean value of BNP was normal (42.5 +/- 35.7 pg/mL). CONCLUSION: In women >70 years of age without heart failure, structural heart disease, and neurohormonal activation, normal TAPSE values are approximately 24 mm.

Clinical and morphological phenotype of the filamin myopathy: a study of 31 German patients.

Mutations in the filamin C gene (FLNC) cause a myofibrillar myopathy (MFM), morphologically characterized by focal myofibrillar destruction and abnormal accumulation of several proteins within skeletal muscle fibres. We studied 31 patients from four German families to evaluate the phenotype of filaminopathy. All patients harboured the same p.W2710X mutation in FLNC. Haplotype analysis suggested a founder mutation in these German filaminopathy families. The mean age at onset of clinical symptoms was 44 +/- 6 years (range, 24-57 years). Slowly progressive muscle weakness was mostly pronounced proximally, initially affecting the lower extremities and involving the upper extremities in the course of disease progression, similar to the distribution of weakness seen in limb-girdle muscular dystrophies (LGMD). Patients frequently developed respiratory muscle weakness. About one-third of the patients showed cardiac abnormalities comprising conduction blocks, tachycardia, diastolic dysfunction and left ventricular hypertrophy indicating a cardiac involvement in filaminopathy. Serum creatine kinase levels varied from normal up to 10-fold of the upper limit. Magnetic resonance imaging studies showed a rather homogenous pattern of muscle involvement in the lower extremities differing from that in other types of MFM. Myopathological features included perturbation of myofibrillar alignment, accumulation of granulofilamentous material similar to that seen in primary desminopathies and abnormal intracellular protein deposits typical of MFM. Decreased activities of oxidative enzymes and fibre hypertrophy seem to be early features, whereas dystrophic changes were present in advanced stages of filaminopathy. Rimmed vacuoles were detected in only a few cases. The intracellular aggregates were composed of a variety of proteins including filamin C, desmin, myotilin, Xin, dystrophin and sarcoglycans. Therapy is so far limited to symptomatic treatment. The German filaminopathy cohort, the largest group of patients studied so far, shares phenotypic features with LGMD and presents with characteristic histopathological findings of MFM.

Intra-operative cooled-tip radiofrequency linear atrial ablation to treat permanent atrial fibrillation.

AIMS: To demonstrate the safety and efficacy of saline irrigated cooled-tip atrial linear endocardial radiofrequency ablation (SICTRA) concomitant to open-heart surgical procedures in the treatment of permanent atrial fibrillation (AF). METHODS AND RESULTS: Two hundred and twenty-two patients presenting with permanent AF and the need for cardiac surgery were included. In addition to the cardio-surgical procedure [mitral valve (MV) surgery (n = 94), aortic valve replacement (n = 29), bypass surgery (n = 76 including 24 patients with additional MV surgery), and combined procedures (n = 23)] concomitant SICTRA was performed. In 116 patients, the ablation pattern was restricted to the left atrium alone. During the mean follow-up of 29 months, 174 patients (78%) converted to sinusrhythm (SR). In patients with SICTRA restricted to the left atrium conversion rates were not different compared to a biatrial approach (83 vs. 74%, P = 0.47). Thirty-days mortality was found to be 4% (9/222). Post-mortem evaluation revealed 23% of all lesions to be histologically non-transmural. In the overall group, only 4% of patients developed sustained secondary regular atrial arrhythmia. CONCLUSIONS: SICTRA safely and effectively restores stable SR in 78% of patients with permanent AF undergoing open-heart surgery. Rhythm outcome is not influenced by treatment of the right atrium. Sustained regular atrial arrhythmia with the need for invasive treatment strategies occurs in 4% although intra-operative ablation lesions are often non-transmural.