Turgut Brodherr

Publications of Turgut Brodherr

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

  Authors: Stephan Waldmüller, Jeanette Erdmann, Priska Binner, Götz Gelbrich, Sabine Pankuweit, Christian Geier, Bernd Timmermann, Janine Haremza, Andreas Perrot, Steffen Scheer [......] Hendrik Milting, Wulf Blankenfeldt, Richard Reinhardt, Cemil Özcelik, Karl-Josef Osterziel, Markus Loeffler, Bernhard Maisch, Vera Regitz-Zagrosek, Heribert Schunkert, Thomas Scheffold

  European journal of heart failure. 07/2011; 13(11):1185-92.

  Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) can both be due to mutations in the genes encoding β-myosin heavy chain (MYH7) or cardiac myosin-binding protein C (MYBPC3). The aimHypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) can both be due to mutations in the genes encoding β-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. 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. 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.

  Authors: Alfried Germing, Michael Gotzmann, Ricarda Rausse, Turgut Brodherr, Stephan Holt, Michael Lindstaedt, Johannes Dietrich, Ulrich Ranft, Ursula Krämer, Andreas Mügge

  European journal of echocardiography : the journal of the Working Group on Echocardiography of the European Society of Cardiology. 04/2010; 11(8):725-8.

  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 andThe 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. 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). In women >70 years of age without heart failure, structural heart disease, and neurohormonal activation, normal TAPSE values are approximately 24 mm.

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

  Authors: Thomas Deneke, Krishna Khargi, Bernd Lemke, Thomas Lawo, Michael Lindstaedt, Alfried Germing, Turgut Brodherr, Leif Bösche, Andreas Mügge, Axel Laczkovics, Peter H Grewe, Markus Fritz

  European heart journal. 01/2008; 28(23):2909-14.

  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 treatmentAIMS: 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.

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

  Authors: Rudolf A Kley, Yorck Hellenbroich, Peter F M van der Ven, Dieter O Fürst, Angela Huebner, Vera Bruchertseifer, Sören A Peters, Christoph M Heyer, Janbernd Kirschner, Rolf Schröder [......] Klaus Müller, Karen Tolksdorf, Katharina Eger, Alfried Germing, Turgut Brodherr, Conny Reum, Maggie C Walter, Hanns Lochmüller, Uwe-Peter Ketelsen, Matthias Vorgerd

  Brain : a journal of neurology. 01/2008; 130(Pt 12):3250-64.

  Mutations in the filamin C gene (FLNC) cause a myofibrillar myopathy (MFM), morphologically characterized by focal myofibrillar destruction and abnormal accumulation of several proteins withinMutations 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.