Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 5th International Conference on Clinical & Experimental Cardiology Philadelphia, USA.

Day 2 :

  • Track 3: Cardiac Therapeutic Agents
    Track 5: Interventional Cardiology
    Track 6: Cardiac Surgery
Speaker

Chair

Louis Samuels

Thomas Jefferson University School of Medicine
USA

Speaker

Co-Chair

Edmo Gabriel

Unilago School of Medicine, Brazil

Session Introduction

Louis Samuels

Thomas Jefferson University School of Medicine, USA

Title: The recover right trial: Use of the impella rp percutaneous right ventricular assist device: An Hde study

Time : 10:30-10:50

Speaker
Biography:

Louis Samuels graduated Medical School from Hahnemann University (Philadelphia, PA) in 1987 and completed his Cardiothoracic Surgical training in 1995. He joined the faculty of Drexel University as the Surgical Director of Cardiac Transplantation. In 2001, Dr. Samuels and his team implanted the world’s 5th totally implantable electric artificial heart (AbioCor™). In 2003, he joined the Main Line Health System as the Surgical Director of Heart Failure. In addition to cardiac transplantation and LVAD implantation, Dr. Samuels performs CABG and Valvular surgery. In 2012, Dr. Samuels became Professor of Surgery at Thomas Jefferson University School of Medicine. Dr. Samuels has authored over 100 peer reviewed manuscripts and serves as a reviewer for the Annals of Thoracic Surgery. In addition to participating in several clinical trials related to mechanical circulatory support, he continues to serve as a consultant and medical advisor to new technologies currently in trial.

Abstract:

Right Ventricular (RV) failure is a potentially lethal condition in medical and surgical patients with mortality > 50% in the most severe cases. Until now, medical and surgical management included inotropic support and extracorporeal mechanical circulatory assist devices. The RECOVER RIGHT™ trial was designed to investigate the role of a percutaneous RVAD in a subset of patients. The RECOVER RIGHT™ is an FDA approved, prospective, multicenter, single arm study that evaluates the safety and probable benefit of the Impella RP™ in patients with RVF refractory to medical treatment and deemed to require hemodynamic support. Two cohorts of patients were analyzed: Cohort A: Post Implantation from a durable LVAD and Cohort B: Post Cardiotomy or Post-MI Shock. Implantation inclusion criteria were as follows: Cardiac Index (CI) < 2.2 L/min/m2 despite one (or more) high dose inotrope and CVP > 15 mmHg or significant RV dysfunction on echocardiography. The primary endpoint was survival at 30 days or hospital discharge or next therapy. Secondary endpoints included hemodynamic improvement and decreased use of inotropes. 175 patients were screened for eligibility and 30 patients were enrolled: Cohort A= 18 pts, Cohort B= 12 pts. The mean age was 59 years with 23 (77%) male gender. Successful implantation was achieved in 29 of the 30 cases (97%). The average duration of support was 1.5 days; the average flow was 3.2 L/min. Overall, 22 of 30 patients survived (73%). The survival of Cohorts A and B were 83% and 58% respectively. CI index improved in all cases while on support and following support; CVP decreased in all cases while on support and following support. Major Adverse Events were as follows: Pulmonary Embolism=0, Limb Ischemia = 1 (3.3%), Neurologic event= 1 (3.3%), Tricuspid and Pulmonic Valve dysfunction = 1 (3.3%), Hemolysis = 4 (13%), and Bleeding = 18 (60%). The RECOVER RIGHT™ is the first percutaneous RVAD FDA study. The use of Impella RP device was: Reliably deliverable and safe Improved the hemodynamics Led to favorable outcomes The Impella RP may play a pivotal role in the treatment of RVF.

Speaker
Biography:

Yaping Tian, Professor of Department of Clinical Biochemistry, Chinese PLA General Hospital and Military Medical School, Professor of Nankai University, Professor of Tsinghua University. Dr Tian received his Master Degree in Medicine from Chinese PLA Postgraduate Medical School and PhD from Academy of Military Medical Sciences. He had been trained as Postdoctoral Fellow for 2 years in The Queen Elizabeth Hospital, Australia. Dr. Tian has been focusing on the study of the specific serum proteomic profiles and genetic signatures in different diseases, especially on cancer. He also focused on the studies of antioxidants in herbal medicine and free radical biology. Dr. Tian has received more than 20 grants and published more than 300 scientific papers in peer-reviewed journals. He is on the editorial boards of several journals and the chairman of the Clinical Biochemistry and Applied Molecular Biology Association, CSBMB.

Abstract:

The progression of cardiovascular diseases is usually need many years and associate with lipid metabolism disorder and inflammation. Finding the risk and prevention at an early stage(subclinical coronary atherosclerosis) are very important. So we aim to explore the risk factors related with the pathology of cardiovascular system in variety patients. Patients who underwent Computed tomography angiography (CTA) have been studied. A total of 659 were enrolled in this studies. All the subjects enrolled had no clinical cardiovascular disease symptoms. Logistic regression showed apart from age, hypertension, smoking, triglyceride, low-density lipoprotein (LDL) cholesterol, and total bilirubin, Hcy was an independently risk factor of the severity of coronary disease. And Hcy was also found an independent predictor for the presence of calcified plaque. When the participants were divided into 4 groups according to serum Hcy quartiles (Q1-Q4 groups), both the percentage of patients with >50% stenosis and the percentage of patients with calcified plaque were higher in Q4 compared to other groups. The OR of Hcy (>15µmol/L) for >50% stenosis was 2.212 (95% CI=1.119 to 4.375, p=0.022) and the OR for Hcy (>15µmol/L) for calcification was 1.668 (95% CI=1.030 to 2.699, p=0.037) respectively. The correlation between serum lipid profile with carotid intima-media thickness and plaque have been studied. 402 patients without apparent clinical atherosclerosis in a cross-sectional study (mean age 50.16 years; 36.07% female) have been involved. Demographics, anthropometrics, and laboratory data were collected. The presence of carotid IMT and plaque were evaluated by ultrasonography. The results showed that carotid IMT was correlated with LDL-C (r=0.137, p=0.009), non-LDL-C levels (r=0.140, p=0.008) and LDL-C/HDL-C ratio (r=0.169, p=0.001). After adjustment for potential covariates, LDL-C (β=0.099, p=0.030) and LDL-C/HDL-C ratio (β=0.132, p<0.001) were independent variables that interacted on carotid IMT. Other risk factors including age and systolic blood pressure were independently associated with carotid IMT. LDL-C levels, non-HDL-C levels, TC/HDL-C and LDL-C/HDL-C ratios were significantly higher, but HDL-C levels were significantly lower in subjects with carotid plaque than those without it. The subsequent multiple logistic regression analysis showed that HDL-C (OR; 0.236, 95%CI; 0.073-0.758, p=0.015) and LDL-C/HDL-C ratio (OR; 1.535, 95%CI; 1.047-2.124, p=0.037) were significantly associated with the presence of carotid plaque after adjustment of age. Serum microRNAs might be potential biomarkers for subclinical coronary atherosclerosis. Solexa sequencing followed by bioinformatics analysis was used to predict novel miRNAs. 3 novel miRNAs (N1, N2 and N3) have been Screening out and then it were validated by 80 control individuals, 80 AS patients and 80 UAP patients by quantitative reverse transcriptase polymerase chain reaction. The three new microRNAs were all expressed in the three groups. N1 and N3 expressed highest in AS group. The predictive values of N1 with an area under the ROC curve (AUC) of 0.811 (95% confidence interval 0.743-0.880) and N3 with an AUC of 0.748 (95% confidence interval 0.664-0.833) were higher than the high-sensitivity C-reactive protein (hsCRP) with an AUC of 0.617 (95% confidence interval 0.530-0.704) for AS. These studies indicated that serum Hcy and LDL-C/HDL-C ratio represents as an independent index associated with the early stages of atherosclerosis, especially on the subclinical periods. Serum microRNAs might be new potential supplement biomarkers for subclinical coronary atherosclerosis.

Hitoshi Hirose

Thomas Jefferson University Hospital, USA

Title: Miniaturized hemodynamic trans-esophageal echocardiogram (hTEE) for cardiac monitoring

Time : 11:50-12:10

Speaker
Biography:

Hirose has graduated Nagasaki University School of Medicine, Nagasaki Japan in 1990, had general surgery residency in St. Luke’s Roosevelt Hospital, New York, NY and Nagasaki University Hospital. He started cardiovascular surgery training in Japan and then had clinical fellowship in Cleveland Clinic Foundation in 2002-2004. He received PhD from Juntendo University College of Medicine in 2005 for his clinical research regarding cardiac surgery. Then he moved into Philadelphia and has been working as attending physician in the Division of Cardiothoracic Surgery, Thomas Jefferson University since 2009. His major interest include management of cardiogenic shock and mechanical circulatory device, especially ECMO.

Abstract:

In cardiac surgery patient, traditionally, postoperative hemodynamics has been assessed by arterial lines and pulmonary artery catheters. While these instruments are helpful; in hemodynamically unstable patient, echocardiography is the gold standard to assess heart function and dynamics. Obtaining transesophageal echocardiography (TEE) on an emergent basis may be limited by its availability. A miniaturized hemodynamic TEE probe (ImaCor Inc., Garden City, NY) was developed to provide information of cardiac function and filling status. The probe is 5 mm in diameter and leave indwelling maximum 72 hours. The trained personnel can insert this probe and obtain the real time images, which can be used for diagnosis and treatment. The hTEE was used for cardiac monitoring 61 cases between 2011 and 2012. The indications for probe insertion were hemodynamic instability (n=32), ECMO weaning (n=10), VAD alarm (n=1), tamponade (n=14), pulmonary embolism (n=2), and intra-aortic balloon pump wean (n=2). In all 61 cases, we were successfully able to diagnose and treat the etiology of instability based on the hTEE findings without any probe complications. Utilization of the hTEE probe successfully diagnosed and aided therapy in all patients with hemodynamic instability refractory to initial therapy. The hTEE probe can be a valuable diagnostic tool to aid clinicians in the management of hemodynamics in the postoperative period of critically ill patients.

Edmo Gabriel

Unilago School of Medicine, Brazil

Title: Aortic coarctation in adults: The role of extra-anatomic bypass

Time : 12:10-12:30

Speaker
Biography:

Edmo Atique Gabriel has completed his medical school from Catholic University of Campinas and Postdoctoral studies from Federal University of Sao Paulo. He is clinical professor of medicine and cardiovascular research expert. He has published papers in reputed journals and has edited two pioneering cardiovascular books by Springer.

Abstract:

Aortic coarctation is very often deemed as a congenital anomaly which should be addressed surgically in infancy. Nevertheless, some adults are diagnosed with this anomaly when clinical signs of arterial hypertension come up. In current era, value of angiotomography for aortic coarctation in adults has increased and allowed cardiovascular surgeon to design operative plan. In the setting of minimally invasive procedures for aortic diseases, endovascular approach has become standard choice aiming to reduce complications and mortality rate. It comes about that anatomic features of aortic coarctation are of paramount importance to determine feasibility and success rate of endovascular approach. Purpose of this abstract is to address surgical strategies to manage aortic coarctation in adults in case of inadequate anatomic profile. Proposition is to present some real cases and their operative plan with emphasis for extra-anatomic bypass and its principles and pitfalls.

Break: Lunch Break 12:30-13:15 @ Benjamin’s
Speaker
Biography:

Fouad AlMutairi has completed his Ph.D in 2013 from University of Chester in UK. He is American board certified in respiratory care since 2005. He has published more than six papers and has been serving as clinical cardiopulmonary researcher at hospital and university in Saudi Arabia and United Kingdom. He also focused in the study of cardiovascular rehabilitation post CABG.

Abstract:

The most common cause of acute atelectasis is post-surgical atelectasis, characterized by restricted breathing after abdominal or cardiac surgery. Large doses of opioids or sedatives, tight bandages, chest or abdominal pain, abdominal swelling (distention), and immobility of the body increases the risk of acute atelectasis following cardiac surgery. All types of therapy such as IS, coughing and breathing exercises or CPAP have a valuable role play in the prevention or treatment of acute atelectasis. However, the type of therapy that should be used is not completely clear yet. This study aims to clarify the difference of effectiveness between CPAP therapy plus chest physiotherapy (CPT) and IS therapy plus CPT to treat or prevent post-operative atelectasis. Seventy two post cardiac surgery patients who fit the inclusive criteria (smoker, hemodynamicly stable, the lungs are healthy and above 50 years old) participated in this study. The participants were divided randomly in two groups, the control group used IS 15 times per hour plus CPT every four hours for 3 days and the trial group used CPAP via mask (4-6 cmH2O) for half hour every two hours plus CPT every four hours. Both regimens applied only during the waking hours. Inspiratory capacity (IC) in litre was used to compare the two groups of therapy. It was measured by an Incentive Spirometer after the cardiac operation as baseline-test, after 12 hours from the start of each therapy, after 24hours, 48 hours and post therapy. at the same time, Respiratory Rate (RR), Heart Rate (HR) and Saturation of Oxygen via pulse oximetry (SpO2 %) were measured for both groups. Failure was defined as a need for advanced therapy such as mechanical ventilation and Bi-level Positive Airway Pressure (BiPAP). SPSS t-tests were used to examine the difference between the baseline and post therapy. 36 patients participated in each group (57 male and 15 female mean ages; 54 ± 6.8 years). IC was increased significantly in CPAP group ( baseline mean for control group 1.23L and CPAP group 1.41L , post- therapy mean 1.59L and 1.98L respectively, p= 0.005) (figure1). SpO2 was decreased significantly in control group (baseline 97.83%, 97.44%, post-therapy 96.56%, 97.11 respectively, p=0.037) and there was no significant difference in RR and HR. Add Chest Physiotherapy (CPT) to CPAP via mask therapy for half an hour every two hours had better outcomes to re-open collapsed alveoli after major thoracic surgery especially in smoker and elderly patients.

Siavash Saadat

Rutgers – Robert Wood Johnson Medical School, USA

Title: Our experience: Minimally invasive aortic valve replacements

Time : 13:55-14:15

Speaker
Biography:

Siavash Saadat is a third year surgical resident at Rutgers - Robert Wood Johnson Medical School. He is a graduate of University of Connecticut School of Medicine, and completed his undergraduate coursework at Georgetown University. His interests are in adult cardiac surgery and has published research on cardiomyocyte differentiation and pathways leading to vasculogenesis.

Abstract:

The small incisions of minimally invasive surgery have the proposed benefit of less surgical traumaand an improved cosmetic outcome, corresponding to afaster postoperative recovery. Here, we report our experience performing minimally invasive aortic valve replacements, via a minimally invasive anterior thoracotomy or mini-sternotomy approach, in comparison to conventional sternotomy. A total of 189 aortic valve replacements were completed from January 2012 – December 2013, where82(43.4%) were mini-thoracotomy, 44(23.3%) mini-sternotomy, and 63(33.3%)conventional sternotomy. Analysis of postoperative complications revealed that the mini-thoracotomy approach, when compared to the mini-sternotomy and conventional sternotomy, had alower incidence of prolonged ventilator support [2.4% vs. 11.4% and 11.1%, respectively(p = 0.054)]. Further, the mini-thoracotomy approach, compared to the mini-sternotomy and conventional sternotomy, required a shorter ICU stay [38.3 vs. 62.8 and 92.7 hours, respectively (p<0.05)] and shorter postoperative length of stay [6.5 vs. 9.4 and 9.3 days, respectively(p<0.05)], resulting in an overall shorter hospitalization [8.8 vs. 12.8 and 14.7 days, respectively(p<0.05)]. Incidence of stroke[1.2% vs. 2.3% and 1.6%, respectively(p=1.0)], reoperation for bleeding [4.8% vs. 6.8% and 4.8%, respectively(p=0.84)], renal failure [6.1% vs. 9.1% and 6.4%, respectively(p=0.82)], and atrial fibrillation [21.9% vs. 34.1% and 23.8%, respectively(p=0.34)], were lower in the mini-thoracotomy group compared to the mini-sternotomy and conventional sternotomy; however, these differences were not statistically significant.Overall, minimally invasive techniques demonstrated a trend towards better survival [mini-thoracotomy 2.4%, mini-sternotomy 2.3%, and conventional sternotomy 4.8%(p=0.77)]. Therefore, we believe that minimally invasive aortic valve replacement is a safe and effective alternative to conventional sternotomy.

  • Workshop on
Speaker

Chair

Sergey Suchkov

A.I.Evdokimov Moscow State University of Medicine and Dentistry, Russia

Speaker
Biography:

Evgeny Rosseikin was born in the city of Sevastopol, USSR. In 1994, he graduated from I.M. Sechenov Moscow Medical Academy and was awarded with MD. In 2002, Rosseikin maintained his PhD in B.V. Petrovsky Russian Centre of Surgery. From 2008 till present Rosseikin the chief of surgery in Federal Centre of Cardivascular Surgery in Penza, Russian Federation. Rosseikin is author of 32 publications and 12 patents.

Abstract:

Atherosclerosis is the leading cause of death worldwide. Myocardial infarction causes almost 7.3 million deaths each year worldwide. In spite of optimal interventional and medical therapy, the risk for acute coronary syndromes is still very high, and heart failure remains one of the top killers in the world since the reliable treatments to get the patients healthy and their lives safe are lacking so far. Metabolic risk factors have been increasing due to the westernization and urbanization of lifestyle. This justifiably raises a concern that the incidence of coronary heart disease in the world will increase over time, and indeed, recent epidemiological studies suggest the incidence of acute myocardial infarction is increasing. And despite advances in coronary artery disease treatment and prevention, myocardial damage due to acute myocardial infarction (MI) remains a major cause of morbidity and mortality in the population. And current treatments are more palliative than curative. Over the past two decades there have been dramatic changes in the diagnosis, treatment and prognosis of acute coronary syndrome (ACS). Several new treatment modalities have been added and the prognosis has improved dramatically. Unlike some organs, the heart has a limited ability to regenerate, and dysfunction resulting from significant cardiomyocyte loss under pathophysiological conditions (such as myocardial infarction) can lead to heart failure. Following significant injury, the heart undergoes induced compensation and gradually deteriorates towards impending heart failure. After an extensive myocardial infarction, restoration of heart function in either of the cases depends on the ability of the heart to promote regeneration and prevent adverse ventricular remodeling. And current therapy slows but does not halt the resultant adverse remodeling. Unfortunately, for patients with end-stage heart failure, heart transplantation remains the main alternative, and it is insufficient, mainly because of the limited availability of donor organs. Moreover, translation of basic science into clinical practice has not been a great success. Meanwhile, exciting progress has been made to establish cell transplantation techniques in recent years, and new preclinical studies in large animal models have shed light on the promises and challenges that lie ahead. Stem cell therapy has gained the potential to regenerate or repair infarcted heart tissue and therefore is becoming a promising therapeutic strategy undergoing intensive investigation. For instance, there has been a large increase in basic science activity in cell therapy and a growing portfolio of cell therapy trials. In a reality, regenerating the human heart is a challenge that has engaged researchers and clinicians around the globe for nearly a century. Stem cells hold a great promise for regenerative medicine, especially for replacing cells in infarcted organ that hardly have any intrinsic renewal capacity, including heart. Being more specific, several types of stem cells, manufacturing methods and delivery routes have been tested in different clinical settings but direct comparison between them is challenging and hinders further research. For ischemic heart disease, use of both autologous and allogeneic stem cells is appearing to be growing. Both autologous and allogeneic cell therapies for ischemic heart disease show a similar improvement in left ventricular ejection fraction in myocardial ischemia. For instance, autologous cell can be applied without immunosuppression, and the cells have been exposed to risk factors and aging. Allogeneic cell therapy enables preoperative production of potent cell lines and immediate availability of cell products, allowing off-the-shelf therapy. Moreover, concomitant transplantation of endothelial cells and stem cells can significantly improve the efficacy of cell based heart repair. Cell based gene therapy, in turn, markedly improves the angiogenesis achieved as well. And, moreover, rejuvenating aged stems cells prior to transplantation restores the functional benefits attained. Finally, modulating the cellular environment in aged individuals permits the full functional benefits of stem cell therapy to be realized. The latter is important for the design of future clinical trials. Moreover, after myocardial infarction, the heart undergoes extensive myocardial remodeling through the accumulation of fibrous tissue in both the infarcted and noninfarcted myocardium, which distorts tissue structure, increases tissue stiffness, and accounts for ventricular dysfunction. To monitor the latter, optimal management of myocardial infarction in the subacute and post-infarction periods focuses on improving the discharge planning process, implementing therapies early to prevent recurrent myocardial infarction, and avoiding hospital readmission. In this sense, early noninvasive stress testing is an important risk assessment tool, especially in patients who do not undergo revascularization. Non-invasive imaging would also play a major role for determination of structural myocardial damage and loss of function. And, for sure, secondary prevention regarding drug-based and off-drug therapy is appearing to be dependent on myocardial function. So, structured discharge processes should be used to enhance communication and facilitate the transition from the hospital to the family physician's care. In this sense, nutrition and exercise training as parts of off-drug therapy would play an important role in the rehabilitation. For instance, exercise-based cardiac rehabilitation is an effective and safe therapy to be used in the management of clinically stable people following myocardial infarction or percutaneous coronary intervention or who have heart failure. Future technologies in the area would secure cardiac rehabilitation whilst recruiting higher risk patients and persons-at-risk and re-considering contemporary models of cardiac rehabilitation delivery, whilst identifying effective interventions for enhancing adherence to rehabilitation. However, the number of industry products available for widespread clinical use does not match this magnitude of activity. There are several problems which need to be overcome. First, although the clinical trials mentioned have been shown to be safe, only a relatively small effect on cardiac function has been observed. It has become clear that each cell type applied in cell-based therapy has its own ability for cardiac repair. And functional restoration of damaged myocardium will require a functional cell type with similar phenotype and characteristics of the damaged tissue that can also integrate, survive, and electrically couple to the host. The second concern among this trend would relate to cost-effectiveness, efficacy, reimbursement, and regulation. We would have to focus on the legacy of the latter to move ahead faster and to secure the positive outlook for future treatment of cardiac diseases with stem cell therapies. So, we hypothesize that the paucity of engagement with the clinical community is a key contributor to the lack of commercially successful cell therapy products.

Speaker
Biography:

Matthew L. Springer received his bachelor’s degree from the University of California, Berkeley in 1985 and his Ph.D. from Stanford University in 1992. He remained at Stanford for his postdoctoral research and continued his research there as a senior scientist. In 2003, he joined the faculty of the University of California, San Francisco, where he is currently one of two non-clinicians on the faculty of the Division of Cardiology. He has published extensively about cell and gene therapy approaches to the treatment of cardiovascular disease, as well as the influence of environmental factors including second hand smoke on vascular endothelial function.

Abstract:

Personalized medicine is a term that means different things to different people (indeed, the definition is personalized itself). In the context of “Predictive, Preventive, and Personalized Medicine” (PPPM), it is frequently taken to refer to genetics; i.e., certain patients will respond better to a given drug because of their genotype, or certain patients are predisposed to a particular disease course due to their genetic make-up. However, personalized medicine has particular relevance in autologous cell therapy, envisioned to enable a patient’s own cells to function as therapeutic agents when harvested, expanded, and returned to their bodies. Not just genotype, but chronic non-disease conditions such as age or chronic/acute disease states such as coronary artery disease can profoundly change the potential therapeutic efficacy of such cells. This talk will consider how these issues affect potential cell and gene therapies, and will examine how the concept manifests in an experimental model of autologous cell therapy using circulating angiogenic cells.

Speaker
Biography:

Sergey Suchkov, MD, PhD., Professor in Immunology & Medicine. Personal: Born 11 January 1957, Astrakhan, Russia. Education: MD, Astrakhan State Medical University, Russia, 1980; PhD, Institute of Medical Enzymology, USSR Academy of Medical Sciences, 1985; Doctor Degree, Nat Institute of Immunology, Russia, 2001. Positions held: Post Doc Res Associate, Institute of Medical Enzymology, 1985-87; Senior Research Associate, Koltzov Institute of Developmental Biology, USSR Academy of Sciences, 1987-89; Head of Lab of Immunology, Helmholtz Eye Research Institute in Moscow, 1989-95; Trainee, Lab of Immunology, NEI, NIH, USA, and Lab of Immunology, Wills Eye Hospital, PA, USA; Head, Department for Immunology, Moscow Clinical Research Institute, Moscow Regional Ministry of Health, 1995-2004; Executive Secretary-in-Chief of the Editorial Board, Biomedical Science, 1993-1996; Professor in Medicine and Immunology, I.M. Sechenov First Moscow Medical University and Faculty Chairman & Director of the Department of Preventive, Personalized and Translational Medicine, A.I.Evdokimov Moscow State University of Medicine & Dentistry. Honours: Secretary General, UCC, Cambridge, UK. Memberships: NY Academy of Sciences, USA; EPMA, Brussels, EU; ARVO (USA); ISER (USA); EPMA J., Personalized Medicine Universe, Open J.Autoimmunity and American J.Cardiovascular Res. Editorial Boards; Russian Biochemical and Immunological Society.

Abstract:

The medicine and cardiology, in particular, is undergoing a paradigm shift to strive from the diagnosis and treatment for prediction and prevention. A new systems approach to disease to pay its crucial attention on the trend would result in predictive, preventive and personalized medicine (PPPM) which is defined as: “…the capacity to predict disease development and influence decisions about lifestyle choices or to tailor medical practice to an individual.” To achieve the implementation of PPPM concept into a practice of cardiologists, it is necessary to create a new strategy based upon the subclinical recognition of cardiac biomarkers long before the heart disease clinically manifests itself. This strategy would secure preventive measures whose personalization could have a significant influence on atherosclerotic vascular disease statistics. The first discriminatory step illustrating the PPPM-oriented survey is based on omics- and stem cell-technologies to let a person-at-risk or a cardiac patient a way to become a data carrier. Individuals pre-selected undergo the second step using phenotypic cardiac biomarkers. Among the best-validated predictive and predictive biomarkers are heart-related ones are broadly known. A combination of genomic and proteomic cardiac simple and combinatorial biomarkers are becoming of great significance to predict risks of chronification of the disease, and thus disabling and lethality since most of the ischemic diseases are preceded by a long subclinical (symptom-free) phase in which the patients can be identified by the presence of specific biomarkers. PPPM whilst utilizing a promising concept of biomarkers would offer a real challenge for the future, and next generations will speak about the XXI century as a time, when healthcare services became predictive and preventive, and its outcomes – secured and guaranteed!

Speaker
Biography:

Matthew L. Springer received his bachelor’s degree from the University of California, Berkeley in 1985 and his Ph.D. from Stanford University in 1992. He remained at Stanford for his postdoctoral research and continued his research there as a senior scientist. In 2003, he joined the faculty of the University of California, San Francisco, where he is currently one of two non-clinicians on the faculty of the Division of Cardiology. He has published extensively about cell and gene therapy approaches to the treatment of cardiovascular disease, as well as the influence of environmental factors including secondhand smoke on vascular endothelial function.

Abstract:

Delivery of bone marrow cells (BMCs) to the heart has substantially improved cardiac function in most rodent models of myocardial infarction (MI), but clinical trials of BMC therapy around the world have led to only modest improvements. Rodent models typically involve intra-myocardial injection of BMCs from distinct donor individuals that are young and healthy, unlike autologous BMCs used for clinical trials that are from post-MI individuals who are also typically of advanced age. We hypothesized that the age and post-MI status of the patient could impair the therapeutic efficacy of the BMCs in an autologous cell therapy treatment. Using BMCs from post-MI donor mice, and from old mice, we discovered that both recent donor MI and donor age impaired BMC therapeutic efficacy. In particular, MI led to myocardial inflammation and an increased inflammatory state in the bone marrow, changing the BMC composition and reducing their efficacy. Injection of a general anti-inflammatory drug or a specific interleukin-1 inhibitor to post-MI donor mice prevented this impairment, suggesting intramyocardial injection of post-MI BMCs is equivalent to the delivery of an active inflammatory response that may attack the already-injured myocardium that the therapy is designed to treat. Our findings offer one explanation of why human trials have not matched the success of rodent experiments, and suggest potential strategies to improve the success of clinical autologous BMC therapy. These results also underscore the influence of patient-specific characteristics on the efficacy of their own cells for autologous therapies.

Speaker
Biography:

Galina Belostotskaya was born in 1947 in St. Petersburg (former Leningrad), graduated from Leningrad State University in 1970 and defended her thesis in 1984 on a speciality "Radiobiology". From 1986 to the present day she is working in the Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian academy of sciences as a Senior researcher and the Head of Cytoanalysis centre. In recent years, she has been studying the resident muscle stem cells and published more then 10 papers in Russian Journals and 2 articles in “Cell Cycle” (2014) and Bioelectromagnetics (2014). Being the head of investigations she released 7 specialists and 2 graduate students. The works have been supported by the 10 Russian grants.

Abstract:

A large incoherence of databanks illustrating the rates self-renewal of cardiac cells and the inability to make a background for the low efficiency of post-infarction mammalian myocardial regeneration is associated with the absence of the understanding of biology and behavior of the resident cardiac stem cells (CSCs) in normal and pathological conditions. In culturing of newborn, 20- and 40-day-old Wistar rat myocardial cells (in vitro) and in a cardiac cell suspension (ex vivo) of 1.5-year-old rat, one-year-old bull, adult 4-5-month-old mice C57bl/6N and 45-year-old woman an unknown mode of reproduction of new cardiac cells has been demonstrated. It has been shown that apart from clones resident Isl1+, c-kit+ and Sca1+ CSCs are capable to develop within a population of the mature myocardial cells via forming intracellular bodies. The latter termed and now known as "cell-in-cell structures" are described for immune cells (to be involved into cytophagocytosis and emperipolesis) and for tumors (entosis), but the data concerning a process of stepwise CSCs structures formation are absent. In contrast to known "cell-in-cell structures", СSC development occurs in cytoplasm of the cardiac cells inside the capsule with 3-5 small holes (micropyles) on its surface. For the first time both in vitro and in ex vivo the reproduction and the initial steps of CSCs differentiation inside the capsule located within the host cell with the formation of transit amplifying myocytes (TAMs) had been identified. It has been shown that the process of intracellular development is finished by the capsule rupture to release cardiac biomarker-positive CSCs-derived TAMs. In vitro simulation of myocardial infarction (acidosis and hypoxia) would result in blocking the differentiation of CSCs inside clones, but 10-15 times increased the number of "cell-in-cell structures", formed in vitro by CSCs identified among neonatal rat myocardial cells. However, analysis of cardiac cells suspension (ex vivo) of C57bl/6N mice after returning from a 30-day space flight (Project BION-M1) showed that the flight and microgravity stimulated clone formation without changing the number of intracellular CSCs-structures as compared to the control. The results obtained allowed to hypothesize that the self-renewal of mammalian myocardium should be going both via proliferation and differentiation of CSCs with the formation of clones, and by their division and partial differentiation inside the mature myocardial cells. Moreover, in an intact (healthy) heart, modes of new cardiac cells formation mentioned occur with the similar frequency: approximately 1 event per 100000 of myocardial cells. We assume that a process of the myocardial cell number maintenance studied is appearing to be a dynamic system to exploit two ways for forming of new functionally active cardiac cells. i.e., (i) the development of resident CSCs within the clones, which are localized between the cells of the heart muscle, and (ii) inside the mature cells of the heart with formation of TAMs which after their release from intracellular capsules also finally differentiate between the cells of the myocardium. In case of prolonged microgravity (in the absence of inflammation) restoration of damaged myocardium occurs mainly through the formation of clones. However, aggressive conditions arising during ischemia and infarction, prevent the clone formation, but promote the transition of CSCs for more long intracellular mode of development. We assume that the latter can explain the "tolerance" of CSCs during cardiac disorders.

Speaker
Biography:

Michael Chorny earned his PhD in pharmaceutical sciences at the Hebrew University of Jerusalem. Since 2009 he is an Assistant Professor of Pediatrics at the University of Pennsylvania and the Children’s Hospital of Philadelphia. His research focuses on development and evaluation of biodegradable nanocarriers for targeted delivery of drugs, gene vectors and cells for cardiovascular disease applications and cancer therapy.

Abstract:

Disassembly rates and patterns of nanoparticles used as drug carriers or diagnostic tools are important determinants of their performance and biocompatibility. Thus, understanding them is essential for the design and optimization of nanoparticle formulations for clinical use. Currently available strategies are not applicable to real-time, quantitative nanoparticle disassembly analysis directly in environments of interest, such as the cell interior or biomimetic media. In the present study, a quantitative strategy using Förster resonance energy transfer for monitoring integrity status of nanoparticles in situ was developed and applied for characterizing disassembly of biodegradable polymer-based magnetic nanoparticles in vascular cells and different types of model milieu. This methodology and study results may be relevant for a broad range of biomedical and analytical applications.

  • Young Researchers Forum
Speaker

Chair

Mahazarin Ginwalla

University Hospitals Case Medical Center, USA

Speaker
Biography:

Sumit Sohal is presently pursuing his M.B.B.S course and is posted as an Intern at Government Medical College, Patiala under Baba Farid University of Health sciences. He has been consistent in his academics and has been awarded medals in the subjects of Physiology and Biochemistry. He has headed the literature committee of the annual college festival and presently he is the state General Secretary of IMA-SW (Indian Medical Association-Student Wing), Punjab Chapter. He has served as the co-author of Hindi section in the annual magazine of the college. He has done around 6 research projects and presented them at national conferences.

Abstract:

Non-communicable diseases (NCDs) pose increasingly important public health problems in low-income and middle-income countries (LMICs). In India, NCDs are estimated to account for 60% of total deaths for which cardiovascular diseases are responsible for 26%. Our study will evaluate the knowledge levels, attitude and behavior patterns regarding cardiovascular diseases among medical students studying in a tertiary care center in Punjab. To prepare baseline knowledge of the medical students and compare it with their attitude and behavior patterns. A pretested structured questionnaire using the WHO-NCD STEPwise approach to surveillance (STEPS; STEP 1 and 2 questionnaires) was prepared and used for the interview of the students. Responses were given scores in order to compare and correlate the components. 200 students participated in this study, the age group being 18-21 years with 55% females and 45% males. Study showed high level of knowledge among the students with mean scores of 28.55 out of 30. 52% of students thought cardiovascular diseases were the leading cause of death in the world and 50% thought heart attack was the most common cardiovascular problem in India. 99.5% students wanted to change their lifestyle and every student thought that smoking ban in public was a good idea. 98% students wanted to have a counsellor in the college to direct and educate them. Despite having such high knowledge, 98% of students have had junk food in the past one week. Out of 90 male students, 54.4% have had alcohol once in their life and 36.67% had alcohol in past 6 months. With knowledge par excellence, students were still practicing behavior which was injurious to their health. It is necessary to provide counsellors at college level to motivate the students and deviate them from high risk practices.

Sarbashri Bank

Sinha Institute of Medical Science & Technology, Vidyasagar University, India

Title: Dermcidin isoform-2 induced nullification of the effect of acetyl salicylic acid in platelet aggregation in acute myocardial infarction

Time : 17:45-18:00

Speaker
Biography:

Sarbashri Bank has completed his M.Sc. (gold medalist) in Biochemistry in 2012 at the age of 24 from Vidyasagar University and currently he is pursuing PhD in the area of cardiovascular diseases under the mentorship of Prof. Asru K Sinha in Sinha Institute of Medical Science & Technilogy, Kolkata since July 2012.

Abstract:

The aggregation of platelets on the plaque rupture site on the coronary artery is reported to cause both acute coronary syndromes (ACS) and acute myocardial infarction (AMI). While the inhibition of platelet aggregation by acetyl salicylic acid was reported to produce beneficial effects in ACS, it failed to do in AMI. The concentration of a stress induced protein (dermcidin isoform-2) was much higher in AMI than that in ACS. Incubation of normal platelet rich plasma (PRP) with dermcidin showed one high affinity (Kd = 40 nM) and one low affinity binding sites (Kd = 333 nM). When normal PRP was incubated with 0.4µM dermcidin, the platelets became resistant to the inhibitory effect of aspirin similar to that in the case of AMI. Incubation of PRP from AMI with dermcidin antibody restored the sensitivity of the platelets to the aspirin effect. Incubation of AMI PRP pretreated with 15µM aspirin, a stimulator of the NO synthesis, resulted in the increased production of NO in the platelets that removed the bound dermcidin by 40% from the high affinity binding sites of from AMI platelets. When the same AMI PRP was retreated with 10µM aspirin, the aggregation of platelets was completely inhibited through NO.

Tanima Banerjee

CSIR-Indian Institute of Chemical Biology, India

Title: Study of collagen metabolism markers in rheumatic heart valve disease : Indian sub-population

Time : 18:00-18:15

Speaker
Biography:

Tanima Banerjee has completed her Bachelor of Science & Master degree from Vinoba Bhave University, Hazaribag, India. Currently she is doing her PhD in Cardiovascular disease at CSIR-Indian Institute of Chemical Biology, Kolkata, India. Her primary objective of research is to understand the extracellular matrix remodeling in Rheumatic Heart Disease. Part of the work is already published in a peer–reviewed journal and presented at various national and international meetings. She also has two patents in her name.

Abstract:

Rheumatic Heart Disease (RHD), a chronic acquired heart disorder results from Acute Rheumatic Fever. The disease is primarily a hypersensitive reaction to streptococcal antigens and affects heart valves giving rise to an acute phase where there is fever, joint pain and features of frank heart failure like shortness of breath, palpitation and fatigue. Generally, mitral valve is affected and show thickening and fibrosis with or without calcification. Although RHD is prevalent in developing countries, thousands of new cases are being diagnosed worldwide every year. Many developing countries, as well as indigenous populations within developed countries, still carry a significant burden of rheumatic fever and rheumatic heart disease and there has been a resurgence in efforts to eradicate the diseases in these populations. However, no biochemical markers are available for disease management. In India, rheumatic heart disease (RHD) is responsible for 30 to 40% of cardiovascular disease related hospital admissions. Whether structural remodelling of the rheumatic heart valve leads to altered level of collagen biomarkers are not yet examined. Thus it is required to investigate extracellular matrix remodelling which may help finding biomarkers of rheumatic heart disease subjects. Clinical examination was performed by trained physicians and the data recorded in a structured proforma. The study involved Indian subpopulation of rheumatic heart disease subjects with before and after valve replacement surgery which includes age and sex matched controls. Subjects were evaluated by 2-dimensional transthoracic echocardiography. Patients were classified into two groups- Mitral Stenosis (MS) and Mitral Regurgitation (MR). Immunoassays were assessed to monitor circulating levels of markers of collagen turnover and histopathology was conducted on excised mitral valve leaflets to examine tissue architecture, inflammation, neovascularisation and occurrence of fibrosis. Circulating Plasma PICP and PIIINP concentrations increased significantly (p<0.01) in MS and MR patients compared to controls but decreased gradually over a one year period post mitral valve replacement surgery (p<0.05). PICP was detected in urine of RHD Patients but found undetectable in control urine. In MS, PICP level and MMP-1/TIMP-1 ratio strongly correlated with mitral valve area (r = -0.40; r = 0.49 respectively) and pulmonary artery systolic pressure (r = 0.49; r = -0.49 respectively); while in MR they correlated with left ventricular internal diastolic (r = 0.68; r = -0.48 respectively) and systolic diameters (r = 0.65; r = -0.55 respectively). Receiver operating characteristic curve analysis (ROC) was performed to establish PICP as a better marker (AUC = 0.95; 95% CI = 0.91 - 0.99; p<0.0001). A cut-off > 459 ng /mL for PICP provided 91% sensitivity, 90% specificity and a likelihood ratio of 9 in diagnosing RHD. Occurrence of fibrosis, inflammatory cells, extensive leaflet fibrosis was shown clearly from histopathological studies and arrangement and distribution pattern of collagen Type 1 was confirmed by immunofluorescence localization in mitral valve sections.The increased rate of collagen turnover is high in RHD groups suggesting the role of an ongoing chronic inflammation which results in significant elevation of collagen metabolism biomarkers of RHD and can be clinically used to diagnose or monitor disease progression.

Dipak Kar

CSIR-Indian Institute of Chemical Biology, India

Title: Mechanism of mitochondrial dysfunction in hypertrophic cardiomyocyte

Time : 18:15-18:30

Speaker
Biography:

Dipak Kar has completed his graduation & post graduation from Calcutta University, Kolkata, India. Currently he is doing PhD in Cardiovascular disease from CSIR-Indian Institute of Chemical Biology, Kolkata, India. His primary objective of research is to understand molecular mechanism of mitochondrial dysfunction in hypertrophic cardiomyocytes. Part of the work is already published in peer–reviewed journal and presented at various national and international meetings. He also have one patent in his name.

Abstract:

The present study was undertaken to understand mitochondrial signaling mechanism in hypertrophic cardiomyocytes. Cardiomyocytes were treated with phenylephrine (PE, 100 µM) for 24h to induce cardiac hypertrophy which was assessed by monitoring cell size and marker gene expression. Hypertrophy of cardiomyocytes and remodeling of the mitochondria were prevented by PPARα agonist, fenofibrate. Fenofibrate also corrected deranged fatty acid oxidation genes in mitochondria in hypertrophic cardiomyocytes. Decrease in mitochondrial trans-membrane potential and dynamicity in PE-treated cardiomyocytes were also blocked by fenofibrate. Significant increase in reactive oxygen species (ROS) production and calcium level in cardiac hypertrophic condition was ameliorated by fenofibrate. Furthermore, PE induced impairment of mitochondrial activity and cellular ATP generation were partially checked when cells were co-treated with fenofibrate. Expression of some miRNAs which were found to be putative regulators of VDAC, were altered in hypertrophic cardiomyocytes which were restored when the cells were co-treated with PPARα agonist, fenofibrate. Overall, the results demonstrate that PPARα signaling is critically involved in mitochondrial dysfunction in hypertrophic cardiomyocytes in which miRNAs might play a significant role.

Break: Poster Presentations (Batch II) @ 17:30-18:30

Panel Discussion

Cocktails sponsored by Journal of Cardiovascular Diseases & Diagnosis 18:30-19:30 @ Independence Foyer