A genome-wide association study identifies 6p21 as novel risk locus for dilated cardiomyopathy.

AIMS: Dilated cardiomyopathy (DCM) is one of the leading causes for cardiac transplantations and accounts for up to one-third of all heart failure cases. Since extrinsic and monogenic causes explain only a fraction of all cases, common genetic variants are suspected to contribute to the pathogenesis of DCM, its age of onset, and clinical progression. By a large-scale case-control genome-wide association study we aimed here to identify novel genetic risk loci for DCM. METHODS AND RESULTS: Applying a three-staged study design, we analysed more than 4100 DCM cases and 7600 controls. We identified and successfully replicated multiple single nucleotide polymorphism on chromosome 6p21. In the combined analysis, the most significant association signal was obtained for rs9262636 (P = 4.90 × 10(-9)) located in HCG22, which could again be replicated in an independent cohort. Taking advantage of expression quantitative trait loci (eQTL) as molecular phenotypes, we identified rs9262636 as an eQTL for several closely located genes encoding class I and class II major histocompatibility complex heavy chain receptors. CONCLUSION: The present study reveals a novel genetic susceptibility locus that clearly underlines the role of genetically driven, inflammatory processes in the pathogenesis of idiopathic DCM.

Magnetic resonance imaging findings in acute myocarditis and correlation with immunohistological parameters.

OBJECTIVE: To evaluate the role of MRI in diagnosing acute myocarditis by correlation with immunohistological parameters. METHODS: A total of 131 patients (85 men, 46 women; mean age, 44.9 years) with suspected acute myocarditis were examined by MRI. The relative water content of the left ventricular myocardium as well as relative and late enhancement was correlated with the immunohistological results in biopsy specimens. RESULTS: Myocardial inflammation was confirmed by immunohistology in 82 of the 131 patients investigated and ruled out in 49 patients. The sensitivity, specificity and accuracy for diagnosing myocarditis in patients with immunohistologically proven disease were 48.8%, 73.8% and 57.3%, respectively, for relative enhancement, 58.3%, 57.1% and 57.9% for relative water content, and 30.6%, 88.1% and 49.6% for late enhancement. A combination of all three parameters had 39,3% sensitivity and 91,3% specificity and 62,7% accuracy. Relative enhancement and late enhancement significantly correlated with the presence of myocarditis but relative oedema did not. CONCLUSION: Relative and late enhancement significantly correlate with the presence of myocarditis, while there is no significant correlation for relative oedema. Myocarditis cannot be reliably diagnosed using any of the three MRI parameters alone but combinations of parameters will improve specificity.

Panic disorders and agoraphobia: side effects of treatment with an implantable cardioverter/defibrillator.

BACKGROUND: Implantable cardioverter/defibrillator (ICD) treatment has reduced the mortality of patients with a high risk of sudden cardiac death. However, ICD discharges may cause anxiety with respect to new discharges and lead to preventive, for example, phobic, behavior. This study evaluated the frequency of panic disorders and agoraphobia in patients with ICD and assessed the risk factors in their development. HYPOTHESIS: Treatment with ICD represents a risk factor in the development of anxiety disorders. METHODS: Ninety patients with ICD were examined using a standardized lifetime Diagnostic Interview of Psychiatric Syndromes (DIPS). This interview makes it possible to estimate the incidence of panic disorders and agoraphobia. The impact of the severity of the underlying cardiac disease, the number of ICD discharges, and the subjective appraisal of the shock experience on the development of panic disorders and agoraphobia was assessed. RESULTS: Fifteen patients (16.7%) developed anxiety disorders after ICD implantation. The incidence was 21% in patients with and 6.9% in patients without ICD discharge. In patients with two or more ICD discharges annually, the incidence of panic disorders and agoraphobia was higher than that in patients with a single ICD discharge annually (62 vs. 10%, p<0.01). The intensity of self-observation of their body was significantly related to the development of anxiety disorders (p<0.001). CONCLUSION: Panic disorders and agoraphobia are frequent side effects of ICD treatment. Risk factors in the development of these disorders are two or more ICD discharges annually and a negative cognitive appraisal of ICD discharges. Therapeutic efforts should aim at reducing the number of ICD discharges and provide early psychological treatment.

Safety of direct stenting with the Endeavor stent: results of the Endeavor II continued access registry.

AIMS: The safety and efficacy of direct stenting with the Endeavor stent is unknown. The acute and 9 month outcome after direct stenting vs. predilatation was tested in a multicentre, prospective, single-arm study. METHODS AND RESULTS: 300 patients were treated with the Endeavor stent for a single, previously untreated coronary artery stenosis (vessel diameter 2.25 to 3.75 mm; lesion length 14 to 27 mm). Predilatation was at discretion of the operator for lesions < 20 mm in length but mandatory for lesions > 20 mm. Angiographic follow-up at 8 months was prespecified for the first 150 consecutive patients. Out of 296 patients, 126 (42.6%) underwent direct stenting and 170 (57.4%) predilatation. Patients in the direct stenting group were younger (62.9 years vs 65.3 years, P=0.04) and lesions were predictably more proximally located and shorter (14.29 mm vs 18.16 mm, P<0.0001), with larger pre-procedural minimum lumen diameter. Success rate was 92.9% with direct stenting vs. 95.3% with predilatation (P=0.45). At 8 months, late loss was not significantly different between groups. The rate of MACE at 9 months was 10.6% with direct stenting vs. 10.2% with predilatation (P=1.00). There were no occurrences of stent thrombosis in either group. CONCLUSION: Direct stenting with the Endeavor stent as deemed feasible by the operator, was safe and effective, and comparable to the results of implantation following predilatation.