Day 1 :
University of Pittsburgh School of Medicine,USA
Keynote: Molecular basis of sex-differences in arrhythmia risk or how can Ca2+-overload generate Torsade de Pointes
Time : 10:15-10:55
Guy Salama completed his PhD in Biophysics and Biochemistry and a Post-doctroal fellowship at the University of Pennsylvania. He is a pioneer in the development of optical probes of membrane potential, high spatial and temporal-resolution imaging of electrical activity and Ca2+ transients and the elucidation of arrhyhtmia mechanisms. He has made significant contributions to elucidate the mechanisms underlying sex differences in long QT-related arrhyhtmias and demonstrated the genomic modulation of cardiac ion channels by estrogen. He has published more than 125 papers in top-tiered journals and has served on numerous study sections for the NIH and the AHA. rnrn
Drug-induced Long QT type 2 (LQT2) is a serious public health problem in terms of safety pharmacology, because many cardiac and non-cardiac drugs inhibit the rapid component of the delayed rectifying K+ current, IKr resulting in action potential duration (APD) and QT prolongation resulting in lethal polymorphic ventricular arrhythmias called Torsade de Pointes (TdP). Despite decades of research, the mechanisms of LQT2-related TdP in man, and why women are at a greater risk of TdP, remain controversial. In clinical and rabbit models, female sex confers a considerably greater risk to TdP which has been attributed sex-differences in ‘repolarization reserve’. This theory posits that female hearts have reduced IKr compared to males due to IKr inhibition and stimulation, respectively by estrogen (17β-estradiol, E2) and dihydrotestosterone (DHT). Our group has challenged this theory and shown that Ca2+-overload at the base of female rabbit hearts initiate TdP in drug-induced LQT2. TdP is initiated by early afterdepolarizations (EADs) which appear first at the base of the heart and are preceded by intracellular Ca2+ (Cai) oscillations during prolonged APDs. Adult females have higher L-type Ca2+ current, ICa,L and Na-Ca exchange current, INCX in myocytes from the base of the epicardium (where EADs are initiated) compared to myocytes from the apex, or from the endocardium. The up-regulation of these currents occurs via genomic upregulations (↑Cav1.2α, β2 subunits, and ↑NCX1 and their mRNA) by E2 (0.3-1 nM). Genomic regulation of Cav1.2α, β2 subunits was mediated by estrogen receptor α, ERα but not the β subtype, ERβ. Dual optical mapping of APs and Ca2+ transients (at subcellular spatial resolution (1.5x1.5 µm2)) shows that repolarization delay (bradycardia or LQT2) in female hearts causes Ca2+ overload and synchronous spontaneous sarcoplasmic reticulum (SR) Ca2+ release during systole, initiating EADs at the base of the ventricles. Synchronous systolic Ca2+ elevation from islands of epicardium as small as ~0.5 mm dia. can elicit EADs and TdP. Findings in rabbit hearts are shown for the first time to apply to human sex differences by testing the effects of estrogen in male and female human iPS-CMs and by Western blot analysis of regional heterogeneities of ion channel expression in the heart of adult men, women and post-menopausal women.
Prince Charles Hospital, Australia
Time : 14:10-14:50
Darren Walters has been the Director of Cardiology at The Prince Charles Hospital from 2005, an Interventional Cardiologist from 2001, and Executive Chair of the Prince Charles Hospital Heart and Lung Institute. He also was the Executive Director of the Prince Charles Hospital for 18 months from February 2013 and acted as Executive Director of the RBWH for a period during a time of change and stabilisation. He was trained at The Prince Charles Hospital and then as a Clinical and Research Fellow in Interventional Cardiology at Massachusetts General Hospital, Harvard Medical School, Boston 2000-2001. He is a Professor of Medicine University of Queensland, and a graduate of the UQ Medical School. He has held roles as Chair of the Prince Charles Hospital Medical Advisory Council, Member of the Prince Charles Hospital Executive Council and Chair of the Central Area Cardiac Network. He is past Chair of the Interventional Working Group of the Cardiac Society of Australia and New Zealand and the Cardiac Society representative Chair of the ACS subcommittee of the Australian Resuscitation Council. He is a member of the ILCOR task force on ACS-myocardial infarction. He is involved in International prospective randomised trials and investigator driven translational research in interventional cardiology and is the author of more than 150 peer reviewed papers, abstracts and book chapters. He has been an invited expert in more than half a dozen countries overseas including the USA, Europe, Japan, Hong Kong, Malaysia, Thailand, Singapore and China. He is one of Australia’s leading interventional cardiologist in the field of structural heart disease
Not to be published
- Session 1
University of Heidelberg, Germany
Title: The subcutaneous implantable cardioverter-defibrillator – first single-center experience with other cardiac implantable electronic devices
Time : 11:10-11:40
Kuschyk has completed his medical degree at the University of Münster, Germany at the age of 27. He is the director of Device Therapy at the University Medical Center Mannheim, Germany. He is senior consultant in Cardiology-Electrophysiology. He has published more than 100 papers in reputed journals and has been serving as an editorial board member of repute. He is international procter for S-ICD and CCM. From 2000-2015 he gave > 200 international presentations on device therapy. Center of Excellence for S-ICD. His main clinical research includes: Device therapy for prevention of sudden cardiac death and chronic heart failure.
The subcutaneous implantable cardioverter-defibrillator (S-ICD) is an implantable device for antiarrhythmic therapy with no intravascular leads.We describe the technical feasibility of combining the S-ICD with other cardiac implantable electronic devices (CIEDs), including pacemakers with trans-venous or epicardial electrodes. We also provide the first experience of combining S-ICD with catheter-based therapies including cardiac contractility modulation (CCM) and vagus nerve stimulation (VNS).Between 7/2011 and 11/2014 six patients received a CCM device and S-ICD, three patients with a single-chamber pacemaker using either trans-venous or epicardial pacing electrodes received S-ICD, and one patient with an implanted S-ICD received VNS. In all patients intraoperative S-ICD testing, crosstalk tests and postoperative ergometric testing were performed.In all 10 patients device implantations were successfully performed without complications. S-ICD therapy was shown to be technically feasible with concomitant CIED. Mean follow up was nearly 17 months. S-ICD testing and crosstalk testing before and during exercise enabled device programming across a broad range of test conditions and was associated with no subsequent evidence of adverse device interaction. None of the devices required permanent inactivation or removal and no patient received an inappropriate shock.In suitable patients, combining an S-ICD with CCM or pacemaker may provide an acceptable means to reduce the number of trans-vascular leads. S-ICD appeared safe with CCM over an intermediate follow-up period. Additional prospective randomized controlled trials examining S-ICD in conjunction with CIEDs are warranted.
University of North Carolina, USA
Title: Extrapericardial placement of implantable cardioverter-defibrillator leads: A novel technique for cardiac anti-arrhythmic therapy
Time : 11:40-12:10
Jeko Madjarov, is board-certified in general, vascular/endovascular, and cardiothoracic surgery. His clinical interests include adult cardiac and thoracic surgery; aortic surgery, including complex/endovascular aortic repair; and minimally invasive coronary and thoracic surgery. He is a key member of the complex lead extraction program in the department of cardiac electrophysiology. Dr. Madjarov has several patents in the field of diagnosis and treatment of cardiac arrhythmias, endovascular treatment of aortic disease, and complex chest wall reconstruction.Dr. Madjarov received his medical degree summa cum laude from Sofia Medical University, Bulgaria, and completed a cardiac surgery residency at St. Ekaterina University Hospital, Sofia, Bulgaria. In the U.S., he completed general surgery residencies at Yale-New Haven Hospital, New Haven, CT; and Baystate Medical Center/Tufts University School of Medicine, Springfield, MA. He then completed fellowships in vascular/endovascular surgery and cardiovascular/thoracic surgery at Carolinas Medical Center, Charlotte, NC - under Prof. Francis Robicsek. An active inventor, Dr Madjarov is leading several research studies and is also closely involved in the development of new medical technology. He has authored more than 20 publications in peer-review.
Transvenous pacing leads insertion provides good long-term results for implantable cardioverter-defibrillator (ICD). However many factors like venous occlusion, intracardiac shunting, previous surgery or risk of extraction may prohibit or complicate transvenous ICD lead placement. The indications for nontraditional placement of ICD leads have greatly expanded over the past decade especially with the growing population of Adult Congenital patients. The aim of this study was to evaluate the impact of extrapericardial placement of ICD leads for treating ventricular arrhythmia via AntiTachicardic Pacing (ATP) and/or Defibrillation.In vivo studies were performed in 9 female Yorkshire pigs (weight 46.2+/-6.1 kg). Surgical approach via left mini-thoracotomy. The first custom-made bipolar pacing lead was sutured extrapericardially at the level of the lateral wall of the left ventricle (LV) and the second lead was secured in a similar fashion at the level of the basal aspect of the right ventricle without opening the pericardium. The ICD generator was placed into the chest wall. A standard “Shock on T” pacing scheme induced ventricular fibrillation (VF).All ICD systems had acceptable defibrillation thresholds with energy tested at 21J, 29J, 37J x 5. There was no increase in impedance between the coil and generator. There were no inappropriate discharges. Each successful shock converted VF to normal sinus rhythm. The mean R-wave amplitude was 9 mV +/- 4 mV. The mean pacing impedance was 331 Ohms. The mean threshold was 4.8V @ 1.5ms.Extrapericardial placement of ICD leads has demonstrated good performance with stable defibrillator parameter. It appears to be a simple efficacious technique to ICD therapy and in some clinical situations can overcome limitations of transvenous or epicardial approaches as well as provide the ability to deliver ATP which is in stark contrast to currently available technology.
Prince Sultan Cardiac Centre, Saudi Arabia
Time : 12:10-12:40
Abdullah Al Abdulgader is the Professor of Congenital Cardiology/Electrophysiology and also General Directorate of Health. He has completed his undergraduate in King Faisal University 1991. He is founder and general director in Prince Sultan Cardiac Centre, General Director of King Fahad Hospital. He has received many local and international compliments and awards. A large number of Congratulatory Letters from the Presidents of the various Universities in Saudi and local educational and academic authorities has been received by him. He has got Congratulatory Letter from the Royal Highness Prince Salman Ibn Abdulaziz and Crowned Prince of Saudi Arabia.
Congenital heart defects are the most common congenital anomalies in human. They constitute the leading cause of congenital anomalies related deaths in all nations and contribute to major health as well as economic and psychological burden in individuals and nations worldwide. In spite of the explosive nature of genetics and epigenetics of cardiac dysmorphogenesis there is increasing level of evidence of the significant directive role of epidemiological data. This is due to the extreme complexity of signalling and transcriptional networks involved in heart development which emphasize the critical and complementary nature of epidemiological research to get closer to the absolute facts of human heart development. We, recently, finalized case-control project of epidemiology of Congenital Heart Defects (CHD) in Saudi live born infants. The main objective of this project was to shed light on probable environmental and genetic risk factors implicated in the etiology of Congenital Heart Defects (CHD) in Saudi population. Unique national sample was created representing one of the largest risk factors database in the history. The various genetic and environmental risk factors constituting 7327*412 information matrix. Parents were interviewed about a wide range of genetic, physiological, medical, occupational and environmental factors that occurred during the critical embryogenesis period. New insights and associations were discovered. This comprehensive database should encourage the international congenital heart community for complementary resources of knowledge in the field aimed toward historical collaboration to abort the process of cardiac dysmorphogenesis in human.
University of Pittsburgh,USA
Title: Relaxin suppresses atrial fibrillation (AF) in spontaneously hypertensive (SHR) and aged rats through electrical and extracellular matrix remodeling via Wnt signaling pathways
Time : 12:40-13:10
Guy Salama completed his PhD in Biophysics and Biochemistry and a postdoctroal fellowship at the University of Pennsylvania. He is a pioneer in the development of optical probes of membrane potential, high spatial and temporal-resolution imaging of electrical activity and Ca2+ transients and the elucidation of arrhyhtmia mechanisms. Dr. Salama has made significant contributions to elucidate the mechanisms underlying sex differences in long QT-related arrhyhtmias and demonstrated the genomic modulation of cardiac ion channels by estrogen. He has published more than 125 papers in top-tiered journals and has served on numerous study sections for the NIH and the AHA.
Relaxin, a hormone first described in pregnancy, has more recently been shown to have important cardiovascular effects. Relaxin activates a wide range of signaling pathways through its receptors, RXFP1/2 which are expressed in most organs. RXFP1 signaling stimulates cAMP, NO and several growth factors and inhibits angiotensin-II and TGF-β effects. RLX increases systemic arterial compliance and reverses fibrosis in multiple organs. In the RELAX-AHF trials, patients with acute decompensated heart failure (HF) received RLX (i.v. 2-days) resulting in reduced mortality (37%, 6-months-later) compared to standard of care. Our studies showed that RLX suppresses atrial fibrillation in spontaneously hypertensive and in aged rats through a marked increase in conduction velocity (CV). CV elevation was associated with the remodeling of the extracellular matrix (↓fibrosis: ↓collagen I&III, ↓TGFβ-1, ↓SMA-α, ↑MMP-6&9) and of electrical properties (↑Connexin43 (Cx43) phosphorylation, ↑INa, ↑Nav1.5). Here, we show for the first time a close interplay between RLX and Wnt signaling. Male aged rats (24-months) were treated with RLX (400µg/kd/day, 2-weeks) or a vehicle delivered with implantable mini-pumps. Langendorff hearts were optically mapped, then analyzed by immuno-fluorescence, voltage-clamp and RT-PCR. RLX-treatment increased Wnt1 (80%) and β-catenin (72%) at intercalated disks (ID) and reversed the lateralization of Cx43 (without changing Cx43 levels) increasing and their co-localization with β-catenin at ID. RLX also reduced Wnt3a (83%) and increased Nav1.5 (80%) and INa (46%) (p<0.02, n ≥ 4 hearts/group). These robust genomic effects of RLX may explain its long-lasting protective actions in HF patients who were treated with RLX (iv) for merely 2-days.
Medical Faculty Mannheim of the University of Heidelberg, Germany
Title: Cardiac Contractility Modulation (CCM) and Subcutaneous Defibrillator (S-ICD) - Clinical Evidence, implantation technique, indications/patient selection and pitfalls
Time : 14:50-16:20
Juergen Kuschyk has completed his Medical Degree at the University of Münster, Germany. He is the Director of Device Therapy at the University Medical Center Mannheim, Germany. He is senior consultant in Cardiology-Electrophysiology. He has published more than 100 papers in reputed journals and has been serving as an Editorial Board Member of repute. He is international procter for S-ICD and CCM. From 2000-2015 he gave >200 international presentations on device therapy. His main clinical research includes: Device therapy for prevention of sudden cardiac death and chronic heart failure.
In the last decades, defibrillator therapy has revolutionized treatment of patients at risk for sudden cardiac death. Multiple clinical trials have shown the benefit of implantable cardioverter–defibrillators (ICD) for primary and secondary prevention of sudden cardiac death. Being an entirely subcutaneous system, the S-ICD avoids important periprocedural and long-term complications associated with transvenous implantable cardioverter–defibrillator (TV-ICD) systems. Cardiac contractility modulation (CCM) is a device-based heart failure therapy with 3 intracardiac leads that enhances contractile strength of the myocardium independent of the synchrony of myocardial contraction. CCM signals are non-excitatory high voltage electrical impulses that are applied during the absolute refractory period. CCM has been proven to improve Quality of Life, exercise capacity and left ventricular parameters and might decrease mortality. In this unique and interactive workshop a detailed and stepwise instruction will be offered on implantation technique of S-ICD and CCM systems including life-videos, case reports, voting questions and an approach for the concomitant implantation of both systems. A special section will be dedicated to adaequate patient selection for both systems and future developments will be discussed.
- Video Presentation
Russian New University, Russia
Time : 16:45-17:00
Vladimir I Ermoshkin has completed his graduation from Physics Department of Moscow State University in 1978 and worked in RosNOU as Biophysicist. From 2011, he has published 5 articles on cardiology in prominent magazines, and had 5 oral presentations at medical conferences in Russian Peoples' Friendship University.
A new attempt to study the unknown role of the arteriovenous anastomoses (AVA).The methodology used in this study is an information search in literature, participation in conferences, discussions with Russian leading cardiologists. Researchers consider that the AVA are important for the regulation of blood supply to certain organs. AVA are involved in the mechanism of thermal, humoral and receptors regulation. However, it is believed that the role of small or large AVA in human circulatory system is still poorly understood. We have found that along with the positive role, the anastomoses, especially large AVA, periodically have pathological effects on the cardiovascular system. The device Cardiocode was used for testing. Large arteriovenous anastomoses (AVA) can be opened under the influence of stress. Periodically, the pressure change in the arteries and veins. Vena cava expands, its wall’s tone increases and pulse waves start to path through the AVA along the elastic walls of the vena cava to the right atrium. Mechanical impulses can excite heart from various points of the atria or ventricles, disrupting the sinus rhythm. The results are as follows: Appearance extrasystoles, tachycardia attacks, at the same time the blood flow is blocked on almost all the peripheral segments of circulatory system and edemata appearance. Increased venous pressure stops the capillary circulation, which eventually leads to heart failure, even in a healthy heart. Serious metabolic disorder appears which leads to disease comorbidity and sudden cardiac death (SCD).Unhealthy way of life and presence of large AVA can sometimes lead to a variety of diseases. To get rid of the attacks of cardiac arrhythmias and the prevention of SCD we need to find some way to suppress the mechanical waves running through AVA, as “reentry” phenomenon has a mechanical nature. It is necessary to continue studying the AVA to develop new measures for neutralizing the pathological events associated with the AVA.
Kindai University, Japan
Time : 17:00-17:15
Satoru Takeno has graduated from Akita University School of Medicine in 2001. After receiving training for general pediatrics and pediatric cardiology, he completed his postgraduate study at Mahidol University, Thailand. He is an assistant professor at Kindai University, and engages in pediatric electrophysiology and catheter ablation.
Atrioventricular nodal reentrant tachycardia (AVNRT) is one of the common form of supraventricular tachycardia in adult population. The presence of dual AV node physiology is one of the key factors for developing AVNRT, because the existence of the two different pathways caused passive current generated from one to the other (electrotonic interaction), causing the prolongation of the effective refractory period in the fast pathway. Meanwhile, the incidence of AVNRT is relatively uncommon in children. The relative frequency of AVNRT increases with age, suggesting an age-dependent anatomic or functional basis for the development of the tachycardia. It is known that the incidence of dual AV node physiology increases and the effective refractory period in the fast pathway prolongs with age. Those conditions are considered to increase the likelihood of inducing the tachycardia. Morphologically, the length of the rightward nodal extension, a possible anatomic substrate for the slow pathway, also increases with age. Therfore, it is speculated that the morphologic change in the rightward nodal extension brings about electrophysiologic conditions. To verify the hypothesis, we examined the correlation between the length of the slow pathway and the effect of the electrotonic interaction, and it demonstrated that the length of the slow pathway had a strong positive correlation with the effect of the electrotonic interaction. The result supported the idea that the prolongation of the rightward nodal extension had a strong impact on the incidence of AVNRT in children.