Our mission is to become a worldwide reference for education in the field for all professionals involved in the process to dissemintate knowledge & skills of Acute Cardiovascular Care
Our mission is to promote excellence in clinical diagnosis, research, technical development, and education in cardiovascular imaging in Europe.
Our mission: To promote excellence in research, practice, education and policy in cardiovascular health, primary and secondary prevention.
Our goal is to reduce the burden in cardiovascular disease in Europe through percutaneous cardiovascular interventions.
Our Mission is "to improve the quality of life of the population by reducing the impact of cardiac rhythm disturbances and reduce sudden cardiac death"
To improve quality of life and logevity, through better prevention, diagnosis and treatment of heart failure, including the establishment of networks for its management, education and research.
Working Groups goals is to stimulate and disseminate scientific knowledge in different fields of cardiology.
ESC Councils goal is to share knowledge among medical professionals practising in specific cardiology domains.
OUR MISSION: TO REDUCE THE BURDEN OF CARDIOVASCULAR DISEASE
Resources are published as they become available during the congress.
By Michael Stauske (Goettingen, Germany)Access the resources from this presentationAuthors:Michael Stauske1,5, Stefan Wagner1,6, Wener Li1,5, Lukas Cyganek1,5, Simin Chen2,5, Sayed-Mohammad Hasheminasab3, Gerald Wulf4, Lars Maier1,6, Gerd Hasenfuss1,5, Kaomei Guan1,51-Department of Cardiology and Pneumology, 2-Department of Pharmacology, 3-Department of Clinical Pharmacology, 4-Department of Hematology and Oncology, University Medical Center Göttingen, Germany; 5-German Center for Cardiovascular Research (DZHK), partner site Göttingen, Germany; 6-Department of Internal Medicine II, University Hospital Regensburg, Germany
Brugada syndrome (BrS), a cardiac genetic disease, is one of the major causes of sudden cardiac death in healthy young people. However, the underlying electrophysiological and molecular mechanisms have not been completely understood. AimsA major challenge in cardiac translational research is the lack of tissue culture systems replicating human pathology to study disease mechanisms and to identify druggable targets. Aim of this study was to study the pathophysiology and molecular mechanisms of BrS in vitro using patient-specific induced pluripotent stem cells (iPSCs) as a renewable and unlimited source for cardiomyocytes (CMs). Methods and resultsIn this study, iPSCs were generated from a 45-year-old healthy donor and a 50-year-old patient with BrS putatively caused by the heterozygous nonsense mutation (c.C5435A, p.S1812X) in the SCN5A gene encoding the alpha-subunit of the cardiac sodium channel (NaV1.5). The generated iPSCs showed pluripotency and were able to differentiate into spontaneously beating CMs. The SCN5A gene was slightly but not significantly upregulated in BrS-CMs with an allele-balanced expression compared to CMs from control iPSCs (Ctrl-CMs). The full-length NaV1.5 protein was detected in BrS-CMs at a level of 82% compared to Ctrl-CMs. Voltage-gated sodium current (INa) measurements revealed a significantly reduced current with a delayed activation in BrS-CMs compared to Ctrl-CMs, indicating a loss of function of NaV1.5. In BrS-CMs, the intermediate inactivation of sodium channels was slightly but not significantly enhanced whereas steady-state inactivation, recovery from inactivation, and persistent INa were not affected. Action potential measurements showed a significantly reduced upstroke velocity, increased irregularities and a higher beat-to-beat variability of action potential durations in BrS-CMs compared to Ctrl-CMs. Inhibition of NaV1.5 with flecainide in Ctrl-CMs resulted in the increased action potential duration variability suggesting that the increased beat-to-beat variability in BrS-CMs is linked to the reduced INa. However, treatment of BrS-CMs with quinidine, a class I antiarrhythmic agent which is currently investigated for its therapeutic effect on BrS, could not reduce the beat-to-beat variability of action potential durations. ConclusionThese data demonstrate that patient-specific iPSCs can be used to model BrS in vitro and may provide a platform for the development of a personalized drug therapy.
By Rosalinda Madonna (Chieti, Italy)Access the resources from this presentationAuthors:Rosalinda Madonna, MD, PhD, Lyubomir Petrov, MD, PhD, Maria Anna Teberino, BSci, Jean-Pierre Karam, PhD, Francesca Vera Renna, MD, Peter Ferdinandy, MD, PhD, Claudia Montero-Menei, PhD, Seppo Yla-Hertuala, MD, PhD, Raffaele De Caterina, MD, PhDCenter of Excellence on Aging, “G. d’Annunzio” University, Chieti, Italy (R.M.); Heart Failure Research, Texas Heart Institute at St. Luke’s Episcopal Hospital, Houston, Texas (R.M.); Department of Internal Medicine, Cardiology, The University of Texas Health Science Center at Houston, Houston, Texas (R.M.); Institute of Cardiology, Department of Neuroscience and Imaging, “G. d’Annunzio” University, Chieti, Italy (M.A.T., F.V.R., R.D.); INSERM U 1066, Laboratoire d'Ingénierie de la Vectorisation Particulaire, Université d'Angers, Angers, France (J.K., C.M.); Biocenter Kuopio, A. I. Virtanen Institute for Molecular Sciences, Kuopio, Finland (L.P., S.Y.); and Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary (P.F.)
RationaleAdipose tissue-derived mesenchymal stromal cells (AT-MSCs) may contribute to repairing ischemic cardiovascular tissue. The engraftment and survival of transplanted stem cells in the harmful microenvironment of host tissue may be improved by combining such cells with scaffolds to delay apoptosis and enhance their regenerative properties.ObjectivesWe examined whether poly (lactide-co-glycolide) (PLGA) microspheres (PAM) functionalized with vascular endothelial growth factor (VEGF) enhance survival, growth, differentiation and angiogenesis of AT-MSCs. We also analyzed the therapeutic efficacy of transplanted AT-MSCs conjugated with PAM in a murine model of myocardial infarction (MI). MethodsWe used non-functionalized (empty) or VEGF-releasing PAM coated with murine AT-MSCs. Twelve month-old C57 mice underwent coronary artery ligation (Lig), followed by randomization into 6 groups (n=5/group): Sham operation, MI control (saline 20 µL), MI followed by intramyocardial injection with AT-MSCs only (2.5x105 cells/20 µL), or concentrated medium from AT-MSCs (CM, 20 µL), or AT-MSCs (2.5x105 cells/20 µL) conjugated with empty microspheres or VEGF-releasing PAM. ResultsVEGF-releasing PAM incresed proliferation but did not impact osteogenic or adipogenic differentiation of AT-MSCs. AT-MSCs conjugated with VEGF-releasing PAM inhibited apoptosis and were more pro-angiogenic than AT-MSCs alone. AT-MSCs conjugated with VEGF-releasing PAM decreased the area of fibrosis and increased arteriogenesis, number of cardiac-resident Ki-67 positive cells and myocardial fractional shortening when transplanted into the infarcted hearts of C57 mice. All such effects were paralleled by the injection of CM. ConclusionsAT-MSCs conjugated with VEGF-releasing PAM exert a paracrine effect that may have therapeutic applications.
By Griet Jacobs (Leuven, Belgium)Authors:G. Jacobs1, M. Kecskes1, I. Mathar2, R. Vennekens1 - (1) University of Leuven, Department Cellular and Molecular Medicine, Leuven, Belgium (2) University of Heidelberg, Heidelberg, Germany
TRPM4 is a Ca2+-activated, but Ca2+-impermeable, non-selective cation channel and is an important regulator of Ca2+-dependent cell functions , including exocytosis, contraction and cell death. Trpm4 expression has been shown in atrial and ventricular cardiac tissue. Recently, gain-of-function mutations in the Trpm4 gene have been associated with conduction disorders, as Progressive Familial heart Block Type 1, Right Bundle Branch Block and Brugada Syndrome. In this study, the role of TRPM4 was established in the ventricular action potential and the effect on cardiac conduction by use of Trpm4-deficient (Trpm4-/-) mice. Patch-clamp experiments and membrane potential measurements showed that TRPM4 is activated during repolarisation of the ventricular action potential and that the duration of the action potential in cardiomyocytes of Trpm4-/- mice was significantly shorter compared to wild-type (WT) cardiomyocytes. Since TRPM4 influences action potential and increased expression of Trpm4 (due to gain-of-function mutations) is associated with conduction disorders, we further investigated the effect of Trpm4 loss on signal conduction through the heart. Therefore, electrocardiographic intervals were determined in WT and Trpm4-/- mice. In conscious mice, II lead surface ECG was measured via telemetry. RR, PR, QRS and QTc intervals were calculated and no differences were found between the 2 genotypes. To look more in detail for impulse propagation and conduction disorders, intracardiac electrophysiological studies were performed on the mice. Atrial, His and ventricular potentials were analyzed in intracardiac electrograms and atrial-His and His-ventricular intervals were equal in WT and Trpm4-/- mice. Taken together, we conclude that loss of Trpm4 results in shorter ventricular action potentials, but this has no influence on impulse propagation and conduction properties of the heart muscle.
By Jean Paul Duong Van Huyen (Paris, France)Access the resources from this presentationAuthors:JP Duong Van Huyen, M Tible, A Gay, R Guillemain, O Aubert, S Varnous, F Iserin, P Rouvier, A François, D. Vernerey, X Loyer, P Leprince, JP Empana, P Bruneval, A Loupy and X Jouven
AimsRejection is one of the major causes of late cardiac allograft failure and at present can only be diagnosed by invasive endomyocardial biopsies. We sought to determine whether microRNA profiling could serve as a non-invasive biomarker of cardiac allograft rejection.MethodsWe included 113 heart transplant recipients from four referral French institutions (test cohort, n=60, validation cohort, n=53).In the test cohort, we compared patients with acute biopsy-proven allograft rejection (n=30) to matched control patients without rejection (n=30), by assessing microRNAs expression in the heart allograft tissue and patients concomitant serum using RNA extraction and qPCR analysis. Fourteen miRNas were selected on the basis of their implication in allograft rejection, endothelial activation, and inflammation and tissue specificity. Results We identified 7 miRNAs that were differentially expressed between normal and rejecting heart allografts: miR-10a, miR-21, miR-31, miR-92a, miR-142-3p miR-155 and miR-451 (p<0.0001 for all comparisons).Four out of 7 miRNAs also showed differential serologic expression (miR-10a, miR-31, miR-92a, and miR-155) with strong correlation with their tissular expression. The ROC analysis showed that these 4 circulating miRNAs strongly discriminated patients with allograft rejection from patients without rejection: miR-10a (AUC=0.976), miR-31 (AUC=0.932), miR-92a (AUC=0.989) and miR-155 (AUC=0.998, p<0.0001 for all comparisons). We confirmed in the external validation set that these 4 miRNAs highly discriminated patients with rejection from those without. The discrimination capability of the 4 miRNAs remained significant when stratified by rejection diagnosis (T-cell mediated rejection or antibody-mediated rejection) and time post transplant.ConclusionThis study demonstrates a differential expression of miRNA occurs in rejecting allograft patients, not only at the tissue level but also in the serum, suggesting their potential relevance as non-invasive biomarkers in heart transplant rejection.
By Astrid Monfort (Paris, France)Authors:Astrid Monfort, Hélène Ragot, Evelyne Polidano, Régine Merval, Claude Delcayre, Christos Chatziantoniou, Jane-Lise Samuel and Alain Cohen-Solal
ObjectiveThe Notch3 receptor is expressed in vascular smooth muscle cells (VSMC) where it plays a key role in controlling the maturation of VSMC, hence in maintaining the integrity of resistance arteries. Notch3-deficient mice subjected to hypertension developed heart failure (Boulos and al., Hypertension, 2011) through an unknown mechanism. The goal of this study was to unravel the role of the Notch3 signaling pathway in the heart, in response to pressure overload.Methods and ResultsMice deficient for the Notch3 gene (N3-/-) or WT mice were subjected to Angiotensin II (AngII)-induced hypertension (AngII infusion, 1µg/kg/min for 28 days using mini-pump). In response to hypertension, N3-/- mice developed a severe heart failure unlike the WT+AngII mice, as illustrated by a lower shortening fraction (-12%, p<0.05) and a more severe cardiac hypertrophy (+30%, p<0.05) associated with major alterations of the coronary compartment [decreased F-actin content in the media (p<0.05), lack of media hypertrophy]. To rule out a possible congenital effect, RBP-Jκ, the transcriptional factor of the canonical Notch3 pathway, was selectively invalidated in the VSMC (SMMHC-CRE ER T2, RBP-Jκ loxp/loxp) at 4 weeks of age, using tamoxifen. Using the same protocol, we observed that in response to hypertension, mice inactivated for RBP-Jκ in the VSMC developed a severe heart failure with a dramatic decrease in shortening fraction (-49% vs Control + AngII, p<0.001) and a more severe LV dilatation (+32% vs Control + Ang II, p<0.001 ).ConclusionAltogether, these data strongly suggest that alterations of the Notch3/RBP-Jκ signaling pathway in the coronary arteries play a role in the occurrence of heart failure in response to chronic increase in blood pressure.
By Ryuji Okamoto (Tsu, Japan)Authors:Ryuji Okamoto, Itaru Goto, Issei Kobayashi, Naoshi Shimojo, Kaoru Dohi, Mashio Nakamura and Masaaki Ito.Departments of Cardiology and Nephrology, Mie University Graduate School of Medicine
BackgroundElongator protein 2 (ELP2) is known as a STAT3-interacting protein and one of subunits of elongator, which can regulate RNA elongation via its histone acetyltransferase activity. It remains to be solved whether ELP2 plays an important role in cardiac hypertrophy.PurposeOur purpose is to identify new gene mutations that cause familial HCM, which can progresses into dilated-phase HCM (d-HCM) by using next-generation DNA sequencing analysis. MethodsWe examined a patient and her elder brother who both presented with complicated severe HCM and whose parents are married cousins. The elder brother had died suddenly as a boy; his autopsy revealed that he had developed HCM. The patient was diagnosed with HCM, and during the 20-year follow-up, HCM progressed to d-HCM. The patient received a left ventricular-assist device implant, and the patient is currently on a waiting list for cardiac transplantation. The parents are healthy. We hypothesized that a causative allele was transmitted to both the patient and the elder brother as an autosomal recessive mutation that caused familial HCM.Analysis of cDNA from cardiac samples revealed that MYH7, MYBPC3, TNNT2 and TNNI3 sequences from the patient was normal. The patient and each of her parents provided informed written consent for genetic testing. The genome analysis and whole-exome sequencing was performed with samples from each of the three participants. An exome capture kit and a next-generation DNA sequencing analyzer were used to sequence each exon library. Sarcomere organization in H9C2 cells overexpressed with ELP2 and localization of ELP2 in biopsy samples were investigated.ResultsThe gene exome analysis showed 340 single nucleotide polymorphisms (SNPs) that caused amino acid change for which the patient was homozygous and both parents were heterozygous. After excluding all known common (>5%) SNP gene mutations in the SNP Database (dbSNP), a gene of elongator protein 2 (ELP2), encoding one of six elongator subunits, was the only identified gene that is possibly associated with cardiac muscle. The identified missense mutation was a 2385 A>G nucleotide transition in the final exon 22 of ELP2 isoform 2 encoding one of six elongator protein subunits. The resultant E795G substitution replaces a polar carboxylic glutamate with a nonpolar glycine. The H9C2 overexpressed with mutant ELP2 showed a distinct sarcomere organization compared with control cells overexpressed with normal ELP2. Based on immunohistochemistry, the localization of ELP2 was different from in control samples.ConclusionsThese results indicate both that mutations in ELP2 can cause a familial form of HCM and that ELP2 may be a new target for treatment of cardiac hypertrophy.
Basic and Translational Science Hot Line on Cardiac Disease