Biography:

Yiu-Fai Chen has completed his PhD in 1982 from Department of Physiology and Biophysics, University of Illinois (Urbana-Champaign) and postdoctoral training at the University of Alabama at Birmingham (UAB) School of Medicine. He is currently a Professor of Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine at UAB. He has been actively involved in cardiovascular research for more than 30 years and have been continuously funded by NIH and AHA, and pharmaceutical and biotechnology companies since 1985, upon completion of his postdoctoral training. He has published 176 peer-reviewed articles published in high impact journals.

Abstract:

Interleukin-8 receptors A/B (IL8RA/B) are homing device for neutrophils to target injured tissues. We developed an innovative targeted cell therapy using ECs that overexpress IL8RA/B to repair the cardiovascular injury. We transduced rat aortic ECs (RAECs), induced-pluripotent ECs (rat-iPS-ECs), or porcine coronary artery ECs (PCAECs) with adenoviruses carrying IL8RA/B genes. We hypothesize that healthy IL8RA/B-ECs can target injured arteries, thus inhibiting infiltration of neutrophils/macrophages and inflammatory responses, and accelerating re-endothelialization and suppressing the injury-induced neointima formation. In rat model, young male SD rats received balloon injury of the carotid artery and were immediately i.v.transfused with 1) vehicle, 2) 1.5x106 control RAECs or rat-iPS-ECs, or 3) 1.5x106 IL8RA/B-RAECs or rat-iPS-IL8RA/B-ECs. One group of rats were sacrificed 24 hr post injury to measure infiltration of neutrophils/macrophages and pro-inflammatory cytokines expression. Another group was sacrificed 2 wks post injury to measure neointima formation. In pig model, young Yorkshire pigs received stent implantation in the LAD and circumflex coronary arteries and were immediately i.v. transfused with 15x106 IL8RA/B-PCAECs or vehicle. Pigs were sacrificed 4 wks after stenting to measure restenosis. Rats transfused with IL8RA/B-RAECs or rat-iPS-IL8RA/B-ECs had significantly decreased neutrophils/macrophages infiltration, inflammatory cytokines expression, and neointima formation in injured arteries. Pigs transduced with IL8RA/B-PCAECs had reduced injury-induced arterial restenosis. Results indicate that transfused adult ECs or iPS-ECs with overexpression of IL8RA/B mimic the behavior of neutrophils that target to injured vessels, preventing inflammation and restenosis. Targeted delivery of ECs to arteries with endoluminal injury provides a novel strategy for the treatment of cardiovascular diseases.

Biography:

Pampee P. Young is a tenured Associate Professor in the Department of Pathology, Microbiology and Immunology at Vanderbilt University Medical Center. She completed her undergraduate at Rice University in Houston, Tx and obtained her M.D/Ph.D. degrees at UT Southwestern in Dallas, Tx. Her basic science research program in regenerative medicine addresses the role of stem cells and our endogenous repair mechanisms to drive wound healing. Our work is funded by the Veterans Affairs, pharmaceuticals and NIH. Dr. Young also serves as the Medical Director of Transfusion Medicine and Stem Cell Laboratory at Vanderbilt University Hospital and the Veterans Affairs in Nashville.

Abstract:

The Wnt/β-catenin pathway is temporarily activated in the heart following myocardial infarct. The effect of therapeutic inhibition of Wnt pathway on post injury outcome are unknown. Using a newly available, small molecule, GNF6231, which averts Wnt pathway activation by inhibiting Wnt secretion, we sought to investigate whether therapeutic inhibition of the Wnt pathway temporarily after infarct can mitigate post injury cardiac dysfunction and fibrosis, hence reconciling discordant observations from genetic studies. Pharmacologic inhibition of the Wnt pathway by GNF-6231 significantly reduced the decline in cardiac function (∆Fractional Shortening%: 1.4±2.312 in GNF-6231 treated vs. -1.713±3.59 in vehicle-treated), prevented adverse cardiac remodeling, and reduced infarct size (9.07±3.98% vs. 17.18±4.97%). Histologically, Wnt inhibition augmented proliferation of interstitial cells, particularly in the distal myocardium, inhibited cell death, including apoptosis of cardiomyocytes, and reduced myofibroblast proliferation in the peri-infarct region. In vitro studies showed that Wnt inhibition increased proliferation of Sca1+ cardiac progenitors, improved survival of cardiomyocytes, and inhibited collagen I synthesis by cardiac myofibroblasts. Systemic, temporary pharmacologic inhibition of the Wnt pathway following MI resulted in improved function, reduced adverse remodeling and reduced infarct size in mice. Therapeutic Wnt inhibition affected multiple aspects of infarct repair: it promoted proliferation of cardiac progenitors and other interstitial cells, inhibited myofibroblast proliferation, improved cardiomyocyte survival, and reduced collagen I synthesis by myofibroblasts. Our data point to a promising role for Wnt inhibitory therapeutics as a new class of drugs to drive post MI repair and prevent heart failure.

Biography:

Dr Sibel Catirli Enar has completed her MD degree from Istanbul University in 1981.She has become Anestesiology specialist in 1985 and Cardiology specialist in 1992 after completing her education in Ä°stanbul University and Institute of Cardiology (Istanbul University).  She is Associate  Prof.of Cardiology,FESC and FASE.She is working at Turkiye Hospital and Ä°stanbul Memorial Hospital.She is a member of cardiac societies,involved in multicenter trials,and served as speakeror moderator or abstract grader in national and international conferences.She has published more than 25 papers and,contributed to book chapters .She is also serving as associate member at the board of Turkish Society of Cardiology (for 2016-2018).

Abstract:

Systemic hypertension causes hypertensive heart disease.Chronic systemic pressure loading results in left ventricular hypertrophy in order to maintain normal wall stress.In earlier stages of hypertension systolic function is preserved.But in later stages or with concomittant coronary artery disease,systolic function is also impaired.  The echocardiographic findings related with hypertension are as follows:Left ventricular hypertrophy(LVH),leftatrial(LA)dilatation,diastolic dysfunction,systolic dysfunction,mitral anular calcification,aortic sclerosis,aortic root dilatation. LVH is symmetrical in hypertension.   ASE/EAE guidelines and cut off limits for LVH:   LV septal wall thickness>0.9 cm for women and >1.0 cm for men.Mild LVH:LV septal thickness 1.-1.2 cm/1.1-1.3cm.Moderate LVH:1.3-1.5/1.4-1.5cm.Severe LVH:>1.6/>1.7 cm.Left ventricular hypertrophy causes different changes  in longutidunal,radial and circumferential mechanics in patients with hypertensive patients.Longitudinal strain is significantly decreased,while radial strain is increased. Left atrial dilatation is commonly seen in hypertensive patients. Left atrial dilation is related to diastolic dysfunction. Left atrial size is also a predictor of paroxysismal atrial fibrillation in hypertensive patients. Recent studies have shown that measurement of left atrial strain with speckle tracking may be useful in determining left atrial function in hypertensive patients.According to the studies,it has been shown that LA strain  values are lower in hypertensive patients when compared to normals, irrespective to the presence of LA enlargement or LVH.Decrease in SR values are present in all three phases of LA function. Reason for LA dysfunction in hypertensive patients is explained by the chronic pressure exposure of the LA,LA pressure rise and reduction of reservoir and conduit functions. In the earliest stages of the disease,systolic function is preserved unless coronary artery disease accompanies.Small,hypertrophic left ventricule is typical for this form of the disease.    However, recent studies using 2D speckle tracking strain demonstrate that impaired myocardial systolic deformation occurs in hypertensive patients.Therefore,systolic left ventricular longitudinal strain decreases  in the early stages of left ventricular remodelling.     Mitral anular calcification is frequently seen in  chronic hypertensive patients.It is the reason for mild or moderate mitral regurgitation in these patients.  Measures of right ventricular deformation are reduced in patients with LVH secondary to hypertension.So,LVH may cause early sub clinical RV dysfunctionaswell. According to the most recent guidelines,it is stated that initiation or monitoring the response to antihypertensive response is based on clinical parameters. However,periodic evaluation of cardiac function and morphology by echocardiography are necessary because of the progressive charasterstics of hypertensive cardiomyopathy.

Biography:

Dr. Maass joined NYU School of Medicine in 2008 after completing her PhD at the Rheinische Friedrich-Wilhelms-Universität in Bonn, Germany and a postdoctoral fellowship in experimental electrophysiology at Upstate Medical University in Syracuse, NY. She is research assistant professor of medicine at the NYU Leon H. Harney Divison of Cardiology, and specializes in mouse molecular genetics, embryonic stem cell biology and experimental models of cardiovascular development and disease, evidenced by numerous publications. Dr. Maass serves as associate F1000 faculty member for cardiovascular pharmacology and as scientific peer-reviewer, including the American Heart Association’s regenerative cell biology Peer Review Committee.

Abstract:

The majority of cardiac fatalities occur due to cardiac arrhythmias. Clinical data implicate distal parts of the specialized cardiac conduction system, the Purkinje fiber network, as main trigger of ventricular tachyarrhythmia. Owing to the rareness of this cell type, deficiencies in understanding processes governing Purkinje cell differentiation and physiology remain. The discovery of induced cell reprogramming has made generation of target cells from somatic human tissue practical. We recently published a reporter gene based embryonic stem cell model of murine Purkinje cells. Using this cell model, we could perform high throughput transcriptional profiling and compare the expression profile to previous published data obtained from adult hearts. We detected high expression of described Purkinje cell transcription factors, including Tbx3, Tbx5, Irx3, Irx5, Etv1, Hopx, and Nkx2.5. Ongoing work characterizes the top-enriched transcription factors towards their transdifferentiation potential, namely generation of Purkinje cells from pluripotent stem cells or fibroblasts. Towards translational applications, we extended our research to human induced pluripotent stem cells (hiPS). We identified cardiomyocyte subpopulations expressing Purkinje cell markers, including Etv1 and Cntn2 (2.9% Cntn2+TroponinT+; 2.7% Cntn2+Etv1+) and detected increased Cntn2 expression over time. Additionally, we have developed a human iPS Purkinje cell reporter line by targeting the Cntn2 locus with a fluorescent reporter gene using CRISPR/Cas9 technology. Using these complementary approaches, we seek to optimize the generation of cardiac conduction system cells for downstream applications, including screening platforms for urgently needed anti-arrhythmic drugs, as clinical tools in personalized medicine approaches or for regenerative cell replacement therapies.

Biography:

2007: Graduate of Faculty of Medicine, School of Heath Sciences, University of Thessaly, Larissa, Greece. 2011-2012: Performance specialty of pathology in the general hospital of Kozani, Greece.2013-2016: Performance specialty of cardiology in the general hospital of Kilkis, Greece. 2010- The present: Scientific collaborator of the Respiratory Medicine Department and Sleep Laboratory, University Hospital of Larissa, Greece.2013: European Resuscitation Council ALS PROVIDER COURSE2/2016: Doctor of Philosophy degree (PhD) of the University of Thessaly, Larissa, Greece. Doctoral thesis: ‘‘Cardiovascular risk in mild-moderate Obstructive Sleep Apnea Syndrome (OSAS)’’. Oral Presentation of clinical cases (‘‘Ebstein’s anomaly’’) in the Cardiology Symposium entitled ‘Advancements in Cardiology 2015’ held in Veroia, Greece, 24 January 2015.Speech at the 22th National Pulmonology Conference (5-7 December 2013, Athens) entitled: ‘‘Identifying phenotypes of Obstructive Sleep Apnea Syndrome via Hierarchical Cluster Analysis.’’Speech at the 21th National Pulmonology Conference (18-21 October 2012, Athens) entitled: ‘‘The DJ-1 protein as a biomarker in Obstructive Sleep Apnea Syndrome’.’Poster at the 4th Congress of Pathology of Central Greece (29-31 March 2012, Larissa) entitled ‘‘Stevens-Johnson Syndrome -Toxic Epidermal Necrolysis (or Lyell) - Retrospective Study.’’

Abstract:

It is estimated that 30% to 40% of hypertensive patients have OSA, and 50% to 56% of OSA patients have hypertension. Scientific data about the interaction between OSA and hypertension are continuously increasing. However, it had been difficult to clarify the cause-effect relationship between the two disorders. Data from some studies support a dose-response relationship of OSA at baseline and the cumulative incidence of hypertension. In contrast, other studies have reported that the unadjusted risk of hypertension increases in concert with AHI (apnea-hypopnea index), but this association was not significant after adjustment for potential confounding variables. Latest data from a retrospective study published in the ‘‘Journal of Clinical Hypertension’’ have revealed that age, BMI, comorbidity (CCI), daytime oxygen saturation, and indices of hypoxia during sleep are the most precise predictors for hypertension. In contrast, AHI and DI (desaturation index) participated weakly in the statistical model. Therefore, although AHI and DI were independent predictive factors for hypertension, both were not included in the most accurate predictors for development of hypertension. It seems that AHI and DI are more complex measures reflecting the degree of intermittent hypoxia, and therefore are susceptible to variability in the clinical setting. It is suggested that daytime and nocturnal hypoxemia as consequences of chronic intermittent hypoxia play a central role in OSA-related hypertension. In particular, the shift from chronic intermittent hypoxia to daytime and nocturnal hypoxia may represent a direct prelude to the development of hypertension.

Biography:

Dr. Wellnhofer has completed his MD in 1984 at Technical University in Munich and his PhD 2010 at Charité University Medicine Berlin on the field of “modelling and simulation in cardiac imaging”. He has done studies in informatics and statistics as well as health economy. He is clinical cardiologist, scientist and university teacher. His current fields of work are cardiac imaging in particular of coronary atherosclerosis, biomedical informatics and statistics, regulatory issues regarding software as medical device and health technology assessment. He published  more than  90 papers in reputed journals and holds several patents. His h-index is 23

Abstract:

Dobutamine stress CMR (DCMR) is an accurate and safe non-invasive test for coronary artery disease (CAD) with high negative predictive value. Direct catheterization (CA) is still an alternative approach that is incentivized by the current reimbursement policy in many countries. Since long-term outcome and cost data from randomized controlled prospective trials are rarely available when new health technologies emerge, evidence based reimbursement policy requires retrospective data mining and lags behind medical and technical evolution. This paper presents level five HTA data on DCMR based on a long term follow-up of patients with suspected stable CAD (sCAD) who underwent DCMR and controls with direct CA. We expected that a DCMR guided approach would be at least as effective as direct CA with respect to survival and more patient friendly in terms of fewer hospitalizations during follow-up by avoiding direct CA. Generally, we suggest data mining digital documentation of early adoption phases of new technologies as source of evidence. This study was a single center retrospective cohort trial that compares two different pathways for managing patients with sCAD and intermediate event risk. Groups (CMR: 209 pts. CA: 293 pts) were matched by propensity scores. Clinical data were collected from institutional quality assurance and research databases. Median patient follow-up was 7.9 years. Primary clinical endpoints were death and cardiac re-hospitalizations. The cost data were calculated per patient and hospital stay from original resource utilization data provided to the German federal InEK/G-DRG database. We chose cost contribution accounting as method to compare both approaches. 

Biography:

Dr. Maass joined NYU School of Medicine in 2008 after completing her PhD at the Rheinische Friedrich-Wilhelms-Universität in Bonn, Germany and a postdoctoral fellowship in experimental electrophysiology at Upstate Medical University in Syracuse, NY. She is research assistant professor of medicine at the NYU Leon H. Harney Divison of Cardiologyy, and specializes in mouse molecular genetics, embryonic stem cell biology and experimental models of cardiovascular development and disease, evidenced by numerous publications. Dr. Maass serves as associate F1000 faculty member for cardiovascular pharmacology and as scientific peer-reviewer, including the American Heart Association’s regenerative cell biology Peer Review Committee.

Abstract:

The majority of cardiac fatalities occur due to cardiac arrhythmias. Clinical data implicate distal parts of the specialized cardiac conduction system, the Purkinje fiber network, as main trigger of ventricular tachyarrhythmia. Owing to the rareness of this cell type, deficiencies in understanding processes governing Purkinje cell differentiation and physiology remain. The discovery of induced cell reprogramming has made generation of target cells from somatic human tissue practical. We recently published a reporter gene based embryonic stem cell model of murine Purkinje cells. Using this cell model, we could perform high throughput transcriptional profiling and compare the expression profile to previous published data obtained from adult hearts. We detected high expression of described Purkinje cell transcription factors, including Tbx3, Tbx5, Irx3, Irx5, Etv1, Hopx, and Nkx2.5. Ongoing work characterizes the top-enriched transcription factors towards their transdifferentiation potential, namely generation of Purkinje cells from pluripotent stem cells or fibroblasts. Towards translational applications, we extended our research to human induced pluripotent stem cells (hiPS). We identified cardiomyocyte subpopulations expressing Purkinje cell markers, including Etv1 and Cntn2 (2.9% Cntn2+TroponinT+; 2.7% Cntn2+Etv1+) and detected increased Cntn2 expression over time. Additionally, we have developed a human iPS Purkinje cell reporter line by targeting the Cntn2 locus with a fluorescent reporter gene using CRISPR/Cas9 technology. Using these complementary approaches, we seek to optimize the generation of cardiac conduction system cells for downstream applications, including screening platforms for urgently needed anti-arrhythmic drugs, as clinical tools in personalized medicine approaches or for regenerative cell replacement therapies.

Biography:

Guy H Fontaine has made 16 original contributions in the design and the use of the first cardiac pacemakers in the early 60s. He has serendipitously identified ARVD during his contributions to antiarrhythmic surgery in the early 70s. He has developed the technique of Fulguration to replace surgery in the early 80s. He has been one of the “216 individuals who have made a significant contribution to the study of cardiovascular disease since the 14^th century”, one of the “500 greatest geniuses of the 21th century” (USA Books), one of the “100 life time of achievement” (UK Book). He has 900+ publications including 201 book chapters. Reviewer of 23 scientific journals both in basic and clinical science. He has served as a member of the Editorial Board of Circulation during 5 years after reviewing during decades papers for this Journal. He has given 11 master lectures of 90’ each in inland China in 2014. He has developed new techniques of hypothermia for neurologic brain protection in OHCA, stroke and spinal cord injury. He is the first to have resuscitated his wife at home with an external defibrillator (Schiller) still working after 30 years. He has also invented a high-tech device which can be considered as the ultimate in palliative care.

Abstract:

A 5 years old child died suddenly beside his father watching television. The immediate appeal of the EMS and Fire Brigade did not allow resuscitation practiced under ideal conditions. The child had a bipolar, epicardial, dual-chamber PM, for complete AV Block detected in utero. A lead fracture discovered during follow-up led to unipolarize the atrial lead system.. However, another lead fracture was also visible at the bifurcation of the ventricular lead system. Nevertheless pacing of both atrial and ventricular chambers was OK.  LVEF was borderline lower limit can be explained by abnormal area of contraction near the LV apex. The case is still in Court after failure of two conciliation committees. Two university hospitals, eight lawyers with one PM technician, 17 doctors and cardiologists, four experts including two super-experts (including GF) were involved. Up to now this case has been presented to 212 doctors and cardiologists who have not found the solution. Seven half-days to study a 500-pages file were necessary to completely elucidate the mechanism of this irreversible death. The conclusion which needs knowledge in Medicine, Cardiology, PM technology and heart Pathology (despite absence of autopsy) suffers no alternative...

The case will be presented step by step asking participation of the audience. The first more important document is the last standard ECG recorded before the catastrophe showing a consistent but difficult to see abnormal phenomenon, the second are laboratory data concerning an asymptomatic lupus detected in the mother by specific antibodies which may explain AV block in utero. The third is the standard X-Ray showing the two leads fracture which was the point of major discussion. The last is the post-mortem interrogation of PM memories, which was overlooked by the expert technician of the pacemaker company. 

Biography:

Abstract:

It is estimated that 30% to 40% of hypertensive patients have OSA, and 50% to 56% of OSA patients have hypertension. Scientific data about the interaction between OSA and hypertension are continuously increasing. However, it had been difficult to clarify the cause-effect relationship between the two disorders. Data from some studies support a dose-response relationship of OSA at baseline and the cumulative incidence of hypertension.^1,2 In contrast, other studies have reported that the unadjusted risk of hypertension increases in concert with AHI (apnea-hypopnea index), but this association was not significant after adjustment for potential confounding variables.^3,4 Latest data from a retrospective study published in the ‘‘Journal of Clinical Hypertension’’ have revealed that age, BMI, comorbidity (CCI), daytime oxygen saturation, and indices of hypoxia during sleep are the most precise predictors for hypertension. In contrast, AHI and DI (desaturation index) participated weakly in the statistical model. Therefore, although AHI and DI were independent predictive factors for hypertension, both were not included in the most accurate predictors for development of hypertension. It seems that AHI and DI are more complex measures reflecting the degree of intermittent hypoxia, and therefore are susceptible to variability in the clinical setting. It is suggested that daytime and nocturnal hypoxemia as consequences of chronic intermittent hypoxia play a central role in OSA-related hypertension. In particular, the shift from chronic intermittent hypoxia to daytime and nocturnal hypoxia may represent a direct prelude to the development of hypertension.⁵

Biography:

Oguzhan YILDIZ, MD, has completed his PhD at the age of 29 years from Hacettepe University and postdoctoral studies from University of California, Irvine. He is professor of Medical Pharmacology at Gulhane Faculty of Medicine. He has published more than 60 papers in reputed journals and has been serving as an editorial board member of repute. 

Abstract:

Interest has increased in the use of arterial conduits for CABG significantly in most major cardiac surgery centers around the world, because the number of patients receiving arterial grafts and our knowledge about the biologic characteristics of arterial grafts have increased. In addition, more advanced clinical protocols for the use of grafts have been developed and midterm results with alternative arterial grafts are encouraging. The internal mammary artery (IMA) has been shown to have greater long-term patency for coronary artery bypass grafting when compared with the saphenous vein graft. Because of the superior long-term results of the IMA, other arterial grafts which have recently been advocated include the radial artery (RA), the gastroepiploic artery (GEA), the inferior epigastric artery (IEA), the splenic artery, the subscapular artery, the inferior mesenteric artery, the descending branch of lateral femoral circumflex artery, the intercostal artery and the ulnar artery. One ofthe  various  manifestations  clinically  observed  among  these  arterial  grafts  is  a  different tendency to develop spasm during surgical dissection and during the perioperative period which could be the cause of perioperative morbidity and mortalitiy. For example, there are reports of vasoactive drugs altering IMA graft flow. Moreover, there is accumulating evidence that blood flow in arterial grafts is insufficient in some circumstances. Many vasoconstrictors  (spasmogens)  may  cause  arterial  grafts  spasm.  Accordingly,  antispastic therapy  is  important  in  the  development  of  arterial  grafts  and  the  nature  of  constrictor substances that cause arterial graft spasm needs to be determined. In recent years, the problem of  graft  spasm  has  become  more  frequent  with  the  increasing  use  of  new  arterial  grafts. Therefore, it is essential for surgeons to understand the causes of vascular graft spasm, to improve  patency  rates  and  to  use  the  optimal  vasodilator  in  the  most  appropriate  way  to counteract vasospasm. Surgeons have studied graft pharmacology by measuring the effects of vasodilators on blood flow through arterial grafts before they were attached to the heart. Pharmacologists have also joined the study of graft pharmacology by evaluating endothelial and smooth muscle function  of  bypass  grafts  using  their  standard  in  vitro  method,  the  isolated  vessel  ring preparation in the organ bath. However, results from these in vitro studies need to be carefully extrapolated to the clinical situations, where the conditions of the arterial grafts are complicated. Even so, the organ bath method can provide very useful information about the effects of vasoactive substances in the arterial grafts. Several vasodilators have been tested and various antispastic methods have been suggested to prevent graft spasm; including papaverine, phenoxybenzamine, calcium antagonists and nitrates etc. Choice of a pharmacological agent to overcome the vasospasm encountered in the arterial grafts must be on the basis of pharmacological studies. Accordingly, current state of knowledge based on experiments to study the pharmacological effect of a number of vasoconstrictor and vasodilator substances and the practical application of this knowledge will be summarized.