Reperfusion therapy for ST elevation acute myocardial infarction 2010/2011: current status in 37 ESC countries

Aims Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion therapy in ST-elevation myocardial infarction (STEMI). We conducted this study to evaluate the contemporary status on the use and type of reperfusion therapy in patients admitted with STEMI in the European Society of Cardiology (ESC) member countries. Methods and results A cross-sectional descriptive study based on aggregated country-level data on the use of reperfusion therapy in patients admitted with STEMI during 2010 or 2011. Thirty-seven ESC countries were able to provide data from existing national or regional registries. In countries where no such registries exist, data were based on best expert estimates. Data were collected on the use of STEMI reperfusion treatment and mortality, the numbers of cardiologists, and the availability of PPCI facilities in each country. Our survey provides a brief data summary of the degree of variation in reperfusion therapy across Europe. The number of PPCI procedures varied between countries, ranging from 23 to 884 per million inhabitants. Primary percutaneous coronary intervention and thrombolysis were the dominant reperfusion strategy in 33 and 4 countries, respectively. The mean population served by a single PPCI centre with a 24-h service 7 days a week ranged from 31 300 inhabitants per centre to 6 533 000 inhabitants per centre. Twenty-seven of the total 37 countries participated in a former survey from 2007, and major increases in PPCI utilization were observed in 13 of these countries. Conclusion Large variations in reperfusion treatment are still present across Europe. Countries in Eastern and Southern Europe reported that a substantial number of STEMI patients are not receiving any reperfusion therapy. Implementation of the best reperfusion therapy as recommended in the guidelines should be encourage

RNF213 Rare Variants in Slovakian and Czech Moyamoya Disease Patients.

RNF213/Mysterin has been identified as a susceptibility gene for moyamoya disease, a cerebrovascular disease characterized by occlusive lesions in the circle of Willis. The p.R4810K (rs112735431) variant is a founder polymorphism that is strongly associated with moyamoya disease in East Asia. Many non-p.R4810K rare variants of RNF213 have been identified in white moyamoya disease patients, although the ethnic mutations have not been investigated in this population. In the present study, we screened for RNF213 variants in 19 Slovakian and Czech moyamoya disease patients. A total of 69 RNF213 coding exons were directly sequenced in 18 probands and one relative who suffered from moyamoya disease in Slovakia and the Czech Republic. We previously reported one proband harboring RNF213 p.D4013N. Results from the present study identified four rare variants other than p.D4013N (p.R4019C, p.E4042K, p.V4146A, and p.W4677L) in four of the patients. P.V4146A was determined to be a novel de novo mutation, and p.R4019C and p.E4042K were identified as double mutations inherited on the same allele. P.W4677L, found in two moyamoya disease patients and an unaffected subject in the same pedigree, was a rare single nucleotide polymorphism. Functional analysis showed that RNF213 p.D4013N, p.R4019C and p.V4146A-transfected human umbilical vein endothelial cells displayed significant lowered migration, and RNF213 p.V4146A significantly reduced tube formation, indicating that these are disease-causing mutations. Results from the present study identified RNF213 rare variants in 22.2% (4/18 probands) of Slovakian and Czech moyamoya disease patients, confirming that RNF213 may also be a major causative gene in a relative large population of white patients

Imaging data of II-2 in Family 1.

<p>(A) MRA image. TOF-3D MRA verifies typical steno-occlusive changes of the circle of Willis. Distal T segments of both internal carotid arteries are occluded and basal moyamoya vessels are clearly seen (anteroposterior view, left panel). Typical “puff-of-smoke” look of moyamoya vessels. Internal carotid arteries are relatively hypoplastic compared with the vertebrobasilar system (lateral view, right panel). (B) Digital subtraction angiography. Catheterization angiography of left vertebral artery (left panel), left carotid artery (middle panel), and right carotid artery (right panel). (C) Transcranial color-coded sonography. Severely dampened flow in the M1 segment of the left middle cerebral artery.</p

MAF in database and prediction of functional change of identified RNF213 variants.

<p>MAF in database and prediction of functional change of identified RNF213 variants.</p

Migration assay using HUVECs transfected with <i>RNF213</i> D4013N, R4019C and V4146A.

<p>Representative images are shown in upper panel. The re-endothelialized areas were quantified by imaging analysis (lower panel). “Vector” represents backbone vector, not including <i>RNF213</i>. Data with bars represent mean ± SD (<i>n</i> = 3 or 4). *<i>P</i> < 0.05 compared with vector, #<i>P</i> < 0.05 compared with WT according to Student’s <i>t</i>-test.</p

Identification of <i>RNF213</i> rare variants in three families.

<p>(A) Pedigree chart and genotypes of <i>RNF213</i> rare variants and microsatellite markers of the three families. Filled and unfilled symbols indicate affected and unaffected individuals, respectively. Squares and circles represent males and females, respectively. Arrows indicate index case. (B) Sequence chromatography of the identified <i>RNF213</i> rare variants. (C) Haplotype for p.R4019C and p.E4042K determined by cloning in II-1 in Family 2.</p

Homology of identified RNF213 variants.

<p>Homology of identified RNF213 variants.</p

Schematic diagram of <i>RNF213</i> rare variants identified in MMD patients.

<p>Variants in Asian and white patients are shown above and below the protein, respectively. The five variants identified in MMD patients from this study are shown in bold characters. AA, amino acid; AAA+, ATPase associated with diverse cellular activities domain; RING, RING-finger domain. This figure was modified from the original version described in Reference 6.</p

Tube formation assay of HUVECs transfected with <i>RNF213</i> D4013N and V4146A.

<p>Representative images are shown in upper panel. The tube areas, total tube length, and number of tube branches were quantified by imaging analysis (lower panel). “Vector” represents backbone vector, not including <i>RNF213</i>. Data with bars represent mean ± SD (<i>n</i> = 3). *<i>P</i> < 0.05 compared with vector, #<i>P</i> < 0.05 compared with WT, †<i>P</i> < 0.05 compared with D4013N according to Student’s <i>t</i>-test.</p