Scientific Program

Day 1 :


Anatoly Ryzhikh got his PhD degree at Moscow Engineering Physics Institute (Technical University) degree in 1995 for the design of Implantable Pacemaker for Cardiomyoplasty (active auto-muscle heart circulation support), also he has his own design of abdominal auto-muscle circulation assist device, diagnostics external pacemakers, diagnostic and therapeutic electrophysiological catheters, patch holters hardware and software.


Application of EP catheters for diagnostics and ablation of cardiac arrhythmias becomes more and more widespread. Many manufactures produce such catheters. Unfortunately, efficacy of EP catheters technology is still far from desirable. We have analyzed main weak points of all EP catheters available on the market. There were revealed three important obstacles of present EP devices. First, operators forced to use both hands to manipulate catheters during procedure. For example, operators use second hand to fix every chosen curve position, and do it many times during every procedure. We have changed usual handle design by implementation of auto-lock mechanism. New handle design provides for operator possibility to use only one hand during whole procedure. Second, almost all existing EP catheters have steering problems. Most sensitive is steering not within one plane, like “snaking” or “twisting”. It is happening because of some design issues of distal shaft. Our new unique distal shaft design make catheters steering very predictable exactly within one plane. Third, many applications need smaller diameter of EP catheters. Available on the market EP steerable catheters have minimal diameter by 5F only, that is not enough thin for many cases. We made design of very thin steerable catheters up to 2F, that is enough for all cardiac applications even for child patients. So, we suppose that modern EP steerable catheter should be with auto-lock handle, with in-plane steering distal shaft and with small diameters up to 2F.


Keynote Forum

Richard M. Fleming

Father of Modern Nuclear Cardiology & Nuclear Medicine Omnific Imaging USA

Keynote: FMTVDM©℗ - A Quantum Leap forward for the Fields of Nuclear Cardiology & Nuclear Medicine

Time : 10:40-11:40


Dr. Richard M. Fleming was born and raised in Iowa and is a "Kennedy Kid" receiving advanced scientific training through this program he received a formal education in Calculus and Particle Physics. He has received degrees in Physics, Biology, Chemistry and Psychology graduating second in his class, attended the University of Iowa College of Medicine graduating with High Honors; 1 of 17 Honors IM. He completed his law degree receiving class award for memorandum of law. While at Iowa he participated in human research, studying sodium and hypertension by measuring nerve conduction differentiating parasympathetic vs sympathetic responses. He completed internship, residency and a Cardiology fellowship in Houston where he published several papers on QCA, diets and heart disease and trained in Nuclear Cardiology including both SPECT & PET. He is one of three "certified" in PET imaging following a one year course of study on antimatter. He continued his investigation into the cause of heart disease and is the author and copyright holder of "Inflammation and Heart Disease," has been on The Today Show, MSNBC & 20/20. In 2005 he moved to the West Coast to help teach and train young physicians. His investigations have unmasked errors in the currently employed methods of detecting heart disease and breast cancer and has copyrights in both fields with patents pending on several methods to "quantitatively" detect these diseases thereby decreasing deaths, costs, time and radiation with associated risk of future cancer risks. He is currently expanding the use of these methods in the U.S., Canada, Europe and Asia. He has been involved with several Administrations as they relate to health care. He has published three independent books, Edited a Medical Textbook, has published several chapters in Medical Textbooks, and has more than 60 peer reviewed papers published in medical journals. He has presented more than 60 times in the U.S., Canada, Europe, the Mideast and Asia. He is credited as being the Father of Modern Nuclear Cardiology & Nuclear Medicine and The Theory of Inflammation and Heart Disease.


Background: The foundational work of nuclear cardiology and nuclear medicine began with Blumgarts 1925 study of “circulation time.” The method was actually quantitative yielding measurements of isotope over time. Unfortunately, the field of Nuclear Medicine and later Nuclear Cardiology would yield to an approach of qualitative image interpretation resulting in problems with sensitivity and specificity as do all “qualitative” methods, resulting in a 35% error rate, matching the limitations of anatomic assessment of disease, including but not limited to coronary angiography, mammography, CT/MRI, et cetera.

Methods: Three hundred men and women between ages 21 and 85 years of age were studied in five centers across the U.S. using a “quantitative” and “enhanced” method (FMTVDM©â„—) designed to measure isotope (Sestamibi and Myoview) redistribution to define “wash-in”, “washout” and “normal” redistribution. Results were compared to quantitative coronary angiography (QCA). Using FMTVDM redistribution measurements, percent diameter stenosis (%DS) was then calculated and the calculated %DS used to calculate a “quantified/Fleming coronary flow reserve”© (QCFR/FCFR) using proprietary equations. The result was then compared with the QCA derived measurements using best fit regression analysis.

Results: FMTVDM measurements of Sestamibi and Myoview redistribution produced a parabolic relationship (p<0.01) and showed that both Technetium 99-m isotopes redistribute beginning at 5-minutes post isotope infusion compared with the 60-minute distribution of isotope. Failure to correctly identify this timing of isotope redistribution had resulted in prior erroneous assumptions that Sestamibi and Myoview did not redistribute. Results from this redistribution was then used to calculate coronary artery narrowing (%DS) and QCFR/FCFR using the proprietary patent equations. The resulting “strong” relationship for the coefficient of determination was 0.87582 (p<0.0001).

Conclusion: Qualitative comparisons of nuclear imaging produces a diagnostic error rate of 35% comparable with angiographic errors in reader interpretation and the inability to satisfactorily unmask underlying vulnerable inflammatory plaques (VIPs) responsible for roughly 85% of all myocardial infarctions. FMTVDM©â„— provides the first ever “quantified” and “enhanced” method for measuring coronary artery disease (CAD) beginning with the measurement of isotope redistribution and ending with the calculation of QCFR/FCFR© using the patented proprietary equations. This patented method is applicable to any device capable of measuring isotope activity over time including but not limited to hand-held probes, planar, SPECT and PET. This provides the First “quantitative” and EVOLUTIONARY change for the fields of Nuclear Medicine and Nuclear Cardiology since its inception in 1925.

  • Heart Surgery

Dr. Nicola Fortune is a Medical Doctor who specializes in General Practice with a special interest in cardiology, specifically in the optimal treatment of atrial fibrillation.  Her previous research ‘Clinical Outcome and prognosis of patients with acute pulmonary oedema and congestive cardiac failure’ was presented at the European Society of Cardiology Heart Failure conference 2018 in Vienna.

Dr. Fortune is an experienced Doctor and keen clinician who is a graduate of University College Dublin (UCD) medical school.

The majority of her medical practice has been at University-teaching hospitals in Ireland including St James University Hospital, Dublin, Our Lady of Lourdes Hospital, Drogheda and Cavan General Hospital.

Dr. Fortune has a wide range of international medical experience having previously worked in Fiona Stanley Hospital and Sir Charles Gardiner Hospital in Perth, Australia. She has also lived and directed a humanitarian medical-aid project in St Luke’s Mission Hospital in Mpanshya, Zambia.



Atrial fibrillation is a very common clinical problem. Often it is a frequent cause of hospitalization for the patient admitted via the emergency department or through the acute medical assessment unit. There common symptoms of presentations are palpitation, dyspnea, chest pain, dizziness etc. These patients are often treated optimally with appropriate anticoagulants and heart rate control therapy. Eventually, they underwent electrical cardioversion (DCCV). Despite of appropriate treatment regimen, a patient has a recurrence of atrial fibrillation. A very little is known about the medical comorbidities and function status of these patients. There is therefore an important paucity of the data indicating the prognosis, recurrence and failure or success of electrical DCCV


We sought to investigate the determinants of successful cardioversion in the selective group of patients who were admitted electively for electrical cardioversion (DCCV) in Our Lady of Lourdes hospital last six months i;e from 1st Jan 2017 to 30th June 2017.


We audited the charts of the patient admitted electively for electrical cardioversion in our coronary care unit at Our Lady of Lourdes Hospital. Total of 58 patient had undergone electrical cardioversion during our study period in the last six months, i:e from January 2017 to June 2017. We retrospectively reviewed the case notes of all those patients with atrial fibrillation. Variable used were age, gender, medical comorbidities such as Hypertension, diabetes, Chronic obstructive pulmonary disease, Chronic kidney disease, anemia, ischemic heart disease, cerebrovascular accident or transient ischemic attacks. We calculated CHA2DS VASC score, HAS Bled Score. We looked through their echo study in detail including their ejection function, Left atrial size, Right ventricular dysfunction, any significant valvular disease.


A total of 58 patient’s charts were studied (40 were males and 18 were females) With age group 45yrs -55yrs (12males, 1 female) 55yrs -65yrs (6males, 1female) 65yrs -75yrs (10males, 9 females) 75yrs -85yrs (13males, 7 females) (fig 1). Their comorbidities were recorded. The commonest medical comorbidity was hypertension 68.9% (n40), followed by obesity 39.6%(n23) and then ischemic heart disease 22.41%(n13). Chronic obstructive pulmonary disease in 12.06%(n7). Other less frequent medical comorbidities were diabetes and chronic kidney disease, which has the equal prevalence of 6.89%(n4). Anemia and cerebrovascular accident or transient ischemic attacks were noted in 3.44% and 1.7% patients respectively. CHA2DS VASC Score was recorded in all patients. Likewise, a HAS-BLED score was also charted. Very detailed echocardiogram findings were charted as below. Ejection function of 20-30% was noted in 6 patients, 35-45% in 5 patients, 45-55% in 15 patients and >55% in 27 patients. Echo was not done in 5 patients and limited quality images noted in 2 patients. The left atrial size was reported to be normal in 21 patients (<3.8cm). 12 patients have mild enlargement of the left atrium (4.0-4.5 cm) and 8 and 8 patients have moderately enlarged (4.6-5.0 cm) and severely enlarged (>5.0cm) left atrium respectively. In 9 patient left atrium size cannot be assessed accurately.


The outlook of electrical cardioversion in treatment of atrial fibrillation in the present era remains substantial. There are no historical data available to report on individual determinants of success of electrical cardioversion. In our study we found that normal left atrial size is an independent decisive factor in successful restoration of sinus rhythm from atrial fibrillation followed by optimal blood pressure control (SBP <150 mmhg) and obesity respectively. In another subset of this observational study, we also noted that two or more than two medical comorbidities with moderately enlarged left atrium will have difficulty in restoration of sinus rhythm with electrical cardioversion.


Each patient involved in this study was selected based on criteria identified with in the admission unit. There may be a possibility of selection bias. Patients are assessed in the cardiology clinic or Acute medical assessment unit by our team doctor, if found suitable then will be listed for elective cardioversion. Though, our centre is a district general hospital. However, this is not the only one. There are few other district hospitals in the surrounding vicinity in Drogheda, within close proximity to our catchment area. This may skew the population that attended our emergency services, cardiology services or acute medical assessment unit services. Some patient may seek health care elsewhere. Nonetheless, we believe our sample to be reasonably sizeable and more representative sample could only be achieved, should a disease registry to be established.



Dr. Muhammed Jameesh is a third year General Cardiology Fellow in Heart Hospital at Hamad Medical Corporation (HMC) in Doha, Qatar.

He earned his M.B.B.S from T.D.Medical College in India in 2008, after which he completed his Internal Medicine Residency at HMC which is an ACGME (American College of Graduate Medical Education) accredited training program. He is currently doing General Cardiology fellowship (ACGME accredited) at Heart Hospital, HMC.  

Dr. Muhammed Jameesh distinguished himself as young professor and clinical researcher. He is regularly involved in teaching internal medicine residents from HMC as well as undergraduate medical students from WCMC-Q (Weil Cornel Medical College- Qatar) with a special interest in ECG interpretation and preventive cardiology. He is also a European resuscitation council certified course director and instructor in various life support courses. He has participated in organizing regional conferences and the latest was Gulf Heart Association (GHA) conference in January 2018.


He has great passion for innovations in medical technology in the field of cardiology and he is currently working on two medical devices which are patent pending. His areas of interests in research are in coronary artery disease root cause analysis and prevention, Endovascular medicine and Innovations in cardiology.  He is currently doing research in molecular level association of coronary artery disease and type 2 diabetes mellitus, Association of acute coronary syndromes and ABO blood types.




Syed Raza

Consultant Cardiologist, Awali Hospital, Bahrain

Title: Heart Failure: Management Failures- Who is to be blamed?

Dr Syed  Raza  graduated from Aligarh University in India  in 1993. After completing his postgraduate degree in Medicine from the same university, he moved to the UK for higher specialist studies. He successfully completed MRCP and CCT and later also  awarded Fellow of the Royal College of Physicians of Edinburgh. He was awarded professor John Goodwin prize for outstanding performance in Diploma Cardiology exam  at Hammersmith Hospital, University of London in 2001.  Dr  Raza  is  Fellow  of  American  College  of  Cardiology  ,  American  College  of  Chest  Physicoans  as  well  as  Fellow  of  European  Society  of  Cardiology.  He  is  also  on  the  committee  of  Acute  Cardiovascular  Care.  Heart  Failure  and  Cardiovascular  Imaging (  European  Society of  Cardiology )

He is currently serving as  consultant in Cardiology and Head of the department of Medicine  at Awali Hospital, Bahrain. He is the educational coordinator and  chairman of resuscitation  committee of the hospital. He is the regional coordinator  and examiner for  MRCP  exam for the Royal College of Physicians of Edinburgh. He is external examiner for Arabian Gulf Medical  University. He is also the immediate past chairman of Medical Advisory Committee. He has to his credit  numerous publications and he has presented his work in  different parts of the world. He is peer review author for some well respected International  journals.

He is Review author for abstracts for European Society of Cardiology Annual Congress 2018.


Heart failure (HF) remains a major public health problem that has high incidence and prevalence globally.  It is the leading cause of hospitalization for people of 65 years of age and older, and rates of hospital readmission within 6 months range from 25% to 50%. The personal burden of HF includes debilitating symptoms, frequent rehospitalizations, and high rates of mortality. HF also poses a substantial economic burden, with annual direct costs for the care of HF patients estimated to be between $20 billion and $56 billion.

 A number of studies have documented marked variation in the quality of care judged by specific performance measures and substantial underuse of evidence-based, guideline-recommended HF therapies in patients receiving conventional care. Moreover, patient behavioural factors (such as nonadherence to diet and medications) and economic and social factors frequently contribute to rehospitalizations. The traditional model of care delivery is thought to contribute to frequent hospitalizations because in these brief episodic encounters, little attention may be paid to the common modifiable factors that precipitate many hospitalizations. Patient education, discharge plan, follow up and management at community level are variable and sub optimal. Limited or poor patient participation and involvement in self-care is also a major factor in leading to poor outcome in HF.

As such, there has been much interest in identifying effective methods to improve the quality of care for HF patients while reducing costs. An effective management strategy and a balanced approach is the much needed.



Background: Non-invasive identification of patients with coronary artery disease (CAD) remains a clinical challenge despite the widespread use of imaging and provocative tests and Speckle tracking echocardiography has been validated for assessment of global and regional left ventricular myocardial function which is affected in patients with obstructive CAD

Objective: Early detection of obstructive coronary artery disease using Peak Systolic global longitudinal strain derived by 2-D Speckle Tracking in patients with chronic stable angina

Patients and methods: 75 patients with chronic stable angina were enrolled in this cross sectional study, (Mean age was 56.69 ± 6.96 y, 35 were males), 42.7 % were diabetic and all patients were assessed by thorough history taking, clinical examination,12 lead surface ECG, conventional, speckle Echocardiography and coronary angiography in Mansoura specialized medical hospital over a period of 7 months from march 2017 to October 2017

Results: Statistically significant decrease was found in GLPS-Avg values in patients with obstructive CAD when compared to patients with normal coronary angiography (p<0001) and in patients  with 3 or more risk factors when compared to patients with one or two risk factors (p=0.014), And when syntax score was increasing among patients with obstructive CAD a significant decrease in median GLPS-Avg values was noted (p<0.001), but when regional systolic strain values were compared to affected  coronary arteries no significant difference was found (p=0.844) i.e almost identical correlation between affected segments by speckle tracking and obstructed arteries by coronary angiography.

Multivariate logistic regression analysis showed that GLPS-Avg was found as a predictor for obstructive coronary artery disease in patients with chronic stable angina (p=0.028 with odds ratio 31.4 and 95% CI (1.85-535))

ROC curves were established and cutoff value was determined for GLPS-Avg as -16 with 89.8% sensitivity and 100% specificity

Conclusion: longitudinal strain derived by speckle tracking can be used as non-invasive simple test for evaluation of patients with chronic stable angina and as a predictor for presence or absence of obstructive CAD

 Keywords: Speckle Tracking – Coronary artery disease – Coronary Angiography.

Mathias Allegaert

European certified Perfusionist bij UZ Antwerpen - Freelance perfusionist bij Perfusion Experts

Title: Heat exchange performance of actual and upcoming adult oxygenators

Mathias Allegaert is a European Board Certified Clinical Perfusionist active in different Belgian hospitals. He graduated at the University of Leuven in 2014 as a clinical perfusionist. He has expertise in cardiopulmonary bypass, VAD program is ELSO-coordinator for the University Hospital of Antwerp and reference person for testing perfusion components and techniques in animal lab settings at the University of Antwerp. He is secretary and webmaster of the BelSECT (Belgian Society of Extracorporeal Technology, In 2016 and 2018 he was part of the steering committee of the International Symposium on Perfusion organized by BelSECT.


Statement of the Problem: To standardize the tests for gas exchange capacity and heat exchange capacity of oxygenators used in a cardiopulmonary bypass (CPB) circuit, the guidelines of the Association for the Advancement of Medical Instrumentation (AAMI) standards are used by manufacturers of CPB components(1,2,3,4). Unfortunately, this standardized specification is not qualified at a consistent water flow rate(5). Actual heater cooler units (HCU) use low pressure to achieve the water flow. Since the publication of mycobacterium chimaera prevention guidelines, different measures have been taken which results in a reduction of the water flow: location of the HCU outside the operating room with longer tubing as consequence, other type of tubing with a smaller internal diameter, connectors with shut-off valve. In combination with the difference in heater cooler unit water flow used by the different manufacturers, the benchmarking results might not be applicable in clinical setting. In order to get consistent results, the different oxygenators in this benchmark were tested under the same heater cooler conditions. Methodology & Theoretical Orientation: All manufacturers on the Belgian market were contacted to provide a sample of their actual and/or upcoming oxygenator(s) with integrated arterial filter for testing purposes. The first part of the study was to quantify the water flow reduction through the heat exchange compartment of the oxygenator. The reference flow of the heater cooler unit was compared with the measured flow when the oxygenator was connected. The second part of the study was the time evaluation for rewarming 70 liters of tap water from 18°C to 35° Celsius. Findings: We observed a flow reduction between  0,97% and 61,17% and  rewarming times between 1h09’00” and 1h57’12” (Figure 1). Conclusion & Significance: New guidelines to evaluate heat exchange performance of oxygenators have to be issued to get consistent, clinical reproducible benchmarks.


Dr Hong-tao Wang,MD,an  associate chief physician in division of cardiology, the Second Affiliated Hospital of Xi’an JiaoTong University.A member of Asia Pacific Heart Rhythm Society(ID number:108600896).Focused on the mechanism and management of the role of autonomic nervous system in the initiation and maintainence of atrial fibrillation.Published 2 papers collected by SCI as the first author (IF=4.2 and 1.3).Moreover, a paper  was just published by JACC Clinical Electrophysiology in 2015.Gained Shaanxi Natural Science Fund in 2015.


Background:  Heart failure (HF) and arrhythmia often coexist and share the similar underlying pathogenesis, including autonomic imbalance, electrical remodeling, and inflammatory reactions. Low-level electrical stimulation (LL-ES) rebalances the tone of the autonomic nervous system and has an anti-arrhythmic effect. However, it is unknown whether LL-ES can decrease the inflammatory response and benefit patients suffering from both HF and arrhythmia.

Aim: This study aimed to investigate the anti-arrhythmic and anti-inflammatory effects of LL-ES of aortic root ventricular ganglionated plexi (ARVGP).

Method: Twenty dogs were divided randomly into drug administration (control) and LL-ES groups after performing rapid right ventricle pacing to establish the HF model. The inducing rate of arrhythmia was measured after a programmed electrical procedure at the baseline and drug administration or LL-ES. The bioactive factors of HF, including angiotensin II, TGF-β,mitogen-activated protein kinase (MAPK), and matrix metalloproteinase (MMP), were assessed. Furthermore, ventricular size and left ventricular ejection fraction were determined.

Results: Compared with the control group, the inducing rate of arrhythmia decreased from 40% to 10% after 4 h of LL-ES (P < 0.05). The expression of angiotensin II, TGF-β, MAPK, and MMP was downregulated significantly in the LL-ES group (P < 0.05). Moreover, the volume of the left ventricle and the ejection fraction of the left ventricle in the LL-ES groupchanged little (P > 0.05).

Conclusion: Short-term LL-ES of ARVGP presented both anti-arrhythmic and anti-inflammatory effects and contributed to the treatment of HF and the associated arrhythmia.


Ms. Anastasia Asylia Dinakrisma, MD is graduated from Internal Medicine Department, Faculty Medicine , Universitas Indonesia in 2018. Her experience were  medical doctor in rural area and team leader in community health development programme in rural area Papua, Indonesia from 2008-2012.  This research was her final thesis emphasized her passion on improving clinical cardiology outcome based on basic examination ECG data.



Fragmented QRS (FQRS) on 2 successive leads, which relate to the territory of the main coronary artery on a 12 lead ECG, known as a marker of myocardial scar, ventricular arrhythmia substrate,  ventricular remodelling  and worse coronary  collaterals flow.

Objectives. This research studied  the role of fQRS as one of the risk factors of MACE (cardiac death and reinfarction)  in ACS patients within 30 days observation.

Methods. A cohort retrospective study was conducted by using secondary data  acute coronary syndrome patients in Intensive Cardiac Care Unit Cipto Mangunkusumo Hospital, Indonesia from July 2015 – October 2017.

Result.  Three hundred and fifty three (353) subjects were included from July 2015 - October 2017. Fragmented QRS was found in 60,9 % subjects, more frequent in inferior leads (48,8% ) with mean onset 34 hours. Major adverse cardiac events were higher in fQRS vs non fQRS group  (15,8% vs 5,8 %). Bivariate analysis showed higher probability of 30 days MACE  in ACS patient (RR 2,72, 95% CI 1,3 -5,71). Multivariate analysis were done by using logistic regression with GRACE score (moderate and high risk), low eGFR (< 60 ml/min), low LVEF (< 40%), diabetes mellitus, age more than 45 years and hypertension  as confounding factors, revealed adjusted RR was 2,79 (95% CI 1,29 – 4,43). Low eGFR  was a potential confounder in this study. Fragmented QRS  is a conduction disturbance marker, recorded in  late potential on signal averaged electrocardiogram (SAECG) from  the fibrotic myocardial zone of infarction, which  increase the risk of ventricular arrhythmias and sudden cardiac death in ACS patient. It also increase the  risk of arrhytmia maligna and left ventricle systolic dysfunction higher than non fQRS group, and predictor of poor formation of collateral coronary artery flow.


Conclusion Persistent fQRS developed in ACS during hospitalization  is an independent predictor of 30 days MACE cardiac death and reinfarction.


Dr Kris Rampersad is an independent cultural and literary sustainable development educator, and multimedia producer/publisher, journalist, facilitator, lecturer, trainer & consultant. She has a BA First Class Honours and PhD degrees from the University of the West Indies, Trinidad and Tobago; Diploma in Mass Communications from the Jawaharlal Nehru University, India; Commonwealth Professional Fellowship from the Association of Commonwealth Universities, UK; Nuffield Foundation Fellowship to Wolfson College, Cambridge University and the Foreign Press Centre of Japan along with numerous skills development training in management, leadership, diversity management, ICTs and new media, journalism, communications, fundraising, networking, gender equity, advocacy among others.

She has done extensive work across the connected Americas especially Caribbean and Latin American region in raising appreciation and building capacities of stakeholders at all levels for cultural heritage, diversity, equity and inclusion. All three Caribbean countries recently admitted to the UNESCO World Heritage lists benefitted from her work and she was also a pioneer of the Commonwealth Women Agents of Change initiative, leading the Caribbean agenda for change and educating women in political and other leadership spheres. She has also been actively involved in inspiring youth through literacy and literary appreciation across the Caribbean.


The World Health Organisation Global Hearts initiative acknowledges CardioVascular Disorders as the number one killer in the world. It also recognizes the paucity of information and understanding about cardiovascular disorders, particularly as regards women with adult congenital heart defects (CHD), on right heart failure, transposition of the greater vessels (TGV) the high incidence in the developing world, the potential impact of travel and exposure to prolonged seated immobility, and the journey through diagnosis, treatment and post-surgery recovery challenges.

Through presentation of this incredible journey to symptom manifestation, diagnosis, surgical repair and the equally incredible post-surgery recovery period of heart and body regeneration from this particularly rare compound of congenital defects that surfaced only near mid-life in an adult female, this case story may explode some commonly-held notions of CHDs and illuminate directions for further diagnosis and treatment in general and in relation to adult women in particular. This case of right heart anomalies and failure also point to some startling departures in popular understanding of heart conditions largely drawn from knowledge of left heart anomalies.

Additionally, in a rare zone of survival, it highlights personal efforts to treat with the seemingly little understood post-operative period of a body and its organs readjusting to restructured heart after a lifetime, coping with regeneration and its survival efforts to date. It further aims to highlight some of the challenges and limitations of screening and detecting, particularly in the context of health care in the developing world.



Introduction: Calcific aortic valve disease(CAVD) is a complex pathological process for which no effective therapies currently exist. Transformation of valvular interstitial cells (VICs) to osteoblasts is believed to be one of the most important causes of valve calcification. Recently, emerging evidence suggests that pro-osteogenic MicroRNAs play essential roles in the calcification of the aortic valve. The purpose of this study is to determine whether miR-22 is critically involved in the osteogenic differentiation of VICs, and if so, to determine the molecular mechanisms involved.

Methods and Results: A total of 33 CAVD patients were enrolled in the study. The severity of CAVD was determined by standard echocardiographic methods. To identify the aberrant expression of miRNAs in calcified aortic valve, real-time PCR was performed to detect the expression profiles of osteogenic miRNAs in CAVD patients. Subsequently, we identified miR-22 as one of the most significantly up-regulated miRNAs in calcified aortic valves. Fluorescence in situ hybridization assay showed that miR-22 was expressed throughout the regions of the calcified valves and predominantly localized in VICs, as indicated by the co-expression of vimentin. Elevated miR-22 levels were positively correlated with the expression of OPN (rs=0.820, P<0.01) and Runx2 (rs=0.563, P<0.01) as well as VIC osteogenic differentiation. Furthermore, we identified calcium binding protein 39 (CAB39) as a novel downstream target of miR-22 in VICs, as determined by dual-luciferase reporter assay, real-time PCR, and western blot assays. Furthermore, we found that the CAB39 expression was negatively correlated with the calcification severity in clinical CAVD samples, as determined by immunohistochemical staining analysis. Adenovirus-mediated both gain- and loss-of-function analyses demonstrated that miR-22 is critically involved in the osteogenic differentiation of VICs, specifically through regulating the CAB39-AMPK-mTOR signaling pathway.

Conclusions: MicroRNA-22 serves as a potential inducer of CAVD through inhibiting the CAB39/AMPK/mTOR signaling pathway. These results suggest that miR-22 may serve as a potential therapeutic target for the calcific aortic valve disease.