11 - 14 JUNE 2013

Wednesday, 12 June 2013

Flame of Science... CardioAlexNEWSLETTER

Bibliotheca AlexandrinaAlexandria - Egypt

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Dr. Bove is past president of the American College of Cardiology.AA Bove, MD, PhDInterpreting Troponin levels. Troponin measures have become the standard means of diagnos-ing an acute coronary syndrome and are available for manage-ment of CS and for diagnosis of chest pain in the emergency setting. As the sensitivity of tropo-nin assays improved, it became apparent that there were many false positive measures that often lead to misdiagnosis and to inappropriate management of patients who did not have an ACS in the presence of an elevated troponin level. These findings led to a more detailed analysis of troponin levels in normal populations, and in patients with other diagnoses as well as in athletes who were found to have troponin elevations after strenuous exercise without evidence of myocardial injury. Other conditions that are associ-ated with elevated troponin levels include heart failure, chronic obstructive pulmonary disease, diabetic ketoacidosis and sepsis. Troponin levels in these disorders are often elevated but do not change acutely like the changes found in patients who present with symptoms of an ACS. An important strategy to avoid being misled by elevated troponin levels in non-ACS patients is to examine the overall clinical presentation. Most patient with an ACS have typical onset of chest pain, ECG changes, and hemodynamic changes that point to an ACS. Incorporating the

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Look closer

With XIENCE, the rate of stent thrombosis in patients interrupting DAPT* after 3 months is no higher than in those with no interruption out to 2 years.1

of which 40% were high risk

some point

Safety – supported by the evidence

1. Source: Based on data from the Mega-Meta Analysis of 7 XIENCE trials. Jan 2012. Data on file at Abbott Vascular.

Abbott Vascular International BVBAPark Lane, Culliganlaan 2B, B-1831 Diegem, Belgium. Tel: 32.2.714.14.11 Fax: 32.2.714.14.12

XIENCE is a trademark of the Abbott Group of Companies.

Products intended for use by or under the direction of a physician. Prior to use, it is important to read the package insert thoroughly for instructions for use, warnings and potential complications associated with use of this device. Information contained herein is for distribution for Europe, Middle East and Africa ONLY. Please check the regulatory status of the device before distribution in areas where CE marking is not the regulation in force. All drawings are artist’s representations only and should not be considered as engineering drawings or photographs.

For more information, visit our website at www.AbbottVascular.com© 2012 Abbott. All rights reserved. 1-EH-2-2529-01 08/2012

*DAPT Interruption: aspirin and/or thienopyridine not taken for at least 1 day, for any reason

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Timing of First DAPT Interruption and ALL Stent Thrombosis (ARC Definite/Probable)

Through 2 Years

Interpreting Troponin levels

clinical scenario greatly improves the specificity of the troponin measure. Many patients with stable coronary artery disease have detectable levels of cardiac troponin T, and over 10% have levels above the 99th percentile of a normal population. A history of CAD is common in patients presenting with acute chest pain, and the pre-test probability of AMI in these patients is high. These patient may have chest pain in the absence of an ACS, and require careful evaluation to avoid overdiagnosing this condi-tion based on Troponin assay. Absence of change in Troponin over several hours is an important additional measure that can help to rule out an ACS. Elevated troponin levels are often found after strenuous exercise, and are not related to acute coronary syndromes. Studies after long distance running, or following strenuous exercise on a treadmill demonstrate elevated levels that may persist for up to 24 hours and are not related to an ACS.Patients with severe anemia, hypertension, left ventricular hypertrophy or chronic renal failure also demonstrate elevated

levels of troponin in the absence of an ACS. The graph below (from Omland et al. J Am Coll Cardiol. Feb 13. 2013) shows the distribu-tion of TnI and TnT in a popula-tion of patients with stable coronary disease. Note that most of the patient values are well below the 99th percentile for the normal population.

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Myocardial viability: what is new?Prof. Khalid el nemrImprovement of ischemic left ventricular dysfunction after revascularization is the criterion of viable myocardium which has a major impact in survival of those cardiac patients. There are several methods currently used to assess viability of the myocar-dium including nuclear techniques (with several proto-cols), dobutamine stress echo, and magnetic resonance imaging. These protocols used to assess indicators of viability whether it is perfusion, glucose metabolism, cell membrane, mitochondria, and presence of contractile reserve. Coronary artery disease (CAD) remains the leading cause of morbidity and mortality worldwide, Many patient with ischemic heart failure have viable but dysfunctional myocardium, where a kinetic or severely hypo kinetic myocar-dium keeps the ability to contract if coronary perfusion improves, This myocardial phenomenon of hibernation was described as early as 1978 by Diamond et al. later it was popularized by Rahim-toola and by Braunwald and Rutherford who emphasized the need for its identification and therapy through revasculariza-tion. Q wave is not sensitive nor specific in detecting scarred myocardium .it was thought that Q waves on the ECG indicate full-thickness myocardial infarc-tion (MI), but in fact, there is no relationship between the presence and extent of Q waves after MI and infarct size assessed by myocardial perfusion imaging, and up to 60% of regions with Q waves have viable myocardium detected by imaging technique , ST-segment elevation at rest in leads with Q waves is associated

with more severe wall-motion abnormalities, less contractile reserve and greater end-systolic volume. In the extreme case, this is seen as the persistent ST eleva-tion of aneurysm formation. In contrast, ST elevation developing during exercise is a marker of maintained viability. Exercise induced ST segment elevation in infarct-related leads was found to have 82% sensitivity and 100% specificity in detection of viability by FDG (fluorodeoxyglucose) uptake, Moreover, the presence of reciprocal ST-segment depres-sion in addition to exercise-induced ST segment elevation indicate residual tissue viability with 84% sensitivity and 100% specificity patients with previous MI and 1-vessel disease . To predict improvement of LV function after revascularization, exercise induced ST segment elevation with pseudonormaliza-tion of negative T waves in infarct-related leads had sensitiv-ity of 80% and specificity of 89% , After MI, a low QT dispersion of ≤70 msec had sensitivity of 83% and specificity of 71% to predict residual viability.To detect viabil-ity : i-nuclear imaging by Positron Emission Tomography (PET) (evaluating labeled FDG uptake), (ii)nuclear imaging by Single-photon emission-computed tomography (SPECT) (evaluating perfusion, cell membrane integrity, and intact mitochondria with thallium or technetium-labeled agents), (iii) echocardiog-raphy with dobutamine (to assess contractile reserve), (iv) echocar-diography with intravenous contrast agents (to assess perfusion),(v)in addition, MRI with dobutamine (to assess contrac-tile reserve), and MRI or CT with intravenous contrast agents (to

assess scar tissue) are emerging as promising techniques.And It is obvious that each of these techniques can detect viability by assessing different factors of the myocardial tissue.We are going to discuss several updated educa-

tional points which are important to know for practicing cardiolo-gist with special emphasis on debatable issues in the literature about this issue and where does the evidnce guide us in mid- year 2013

Lipid & AtherosclerosisIntervention

International Session

CME

Live TransmissionElectrophysiology

Endovascular

Special Topics

State of the Art

HypertensionStent For LifeHeart Failure

Diabetes & the HeartImaging

Nuclear ImagingBasic Science Cardiac Surgery

EchocardiographyResearch & PresentJCA

Clinical Cases

Pediatric

Workshop

Wednesday 12 June 2013

Endovascular 2

Main HallEuroPCR @ CardioAlex 1 08:30 - 09:30National Live 1 09:30 - 10:30

10:30 - 11:30C3 @ CardioAlex 01:00 - 01:45Special Topics 3

03:15 - 04:1505:15 - 06:15

ACC @ CardioAlex 2 08:45 - 09:4509:45 - 11:00

Continious Medical Education 1 11:00 - 12:00State of the Art 3 01:00 - 02:15

03:15 - 04:15

Echocardiography 2

Workshop on 4D Echocardiography Hands-On

Workshop on Tissue Doppler Hands-On

08:30 - 10:0010:00 - 12:00

Pediatric Lecture 3 Pediatric Lecture 4 Panel Discussion 1Symposium 4 - Echo 1Symposium 5 - Echo 2

01:00 - 01:45 01:45 - 02:1503:15 - 04:1505:15 - 06:3006:30 - 07:45

Auditorium Hall

Imaging 2

Intervention 3

Imaging 3

EuroPCR @ CardioAlex 2

National Live 2

Intervention 2

Echocardiography 4

Delegate Hall08:30 - 09:3009:30 - 10:30

Stent for Life 1 10:30 - 12:00Heart Failure 01:00 - 02:15

03:15 - 04:1505:15 - 06:15

Hypertension 2State of the Art 2

Diabetes & the Heart

Echocardiography 3

Multi Purpose HallLipid & Atherosclerosis 08:30 - 09:45

09:45 - 10:4510:45 - 12:0001:00 - 02:1503:15 - 04:1505:15 - 06:30

Nuclear Imaging 2Basic Science 2 Nuclear Imaging 3

Cardiac Surgery 1

Training Set RoomClinical Cases 2AstraZeneca Workshop 1ECG WorkshopAstraZeneca Workshop 2Electrophysiology ClubLearn with Horst SevertClinical Cases 3

08:30 - 09:3009:30 - 10:0010:00 - 12:0001:00 - 01:3001:30 - 02:1503:15 - 04:1505:15 - 06:15

08:30 - 09:3009:30 - 11:0011:00 - 12:0001:00 - 02:1503:15 - 04:15

Hall A

Research & Present @ CardioAlex 9Junior CardioAlex Awards 1Research & Present @ CardioAlex 10Junior CardioAlex Awards 2

Research & Present @ CardioAlex 11

09:00 - 10:0010:00 - 11:0011:00 - 12:00

01:00 - 02:00

03:15 - 04:1505:15 - 06:15Research & Present @ CardioAlex 12

Junior CardioAlex Awards 3 06:15 - 07:15

Research & Present @ CardioAlex 8 08:30 - 09:00

PAFCIC How Should I Treat ?

Small Theatre Lecture Hall

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CardioAlexNEWS

Wednesday, 12 JUNE 2013

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Alexander PorkhomenkoPercutaneous coronary interven-tion (PCI) represents the most commonly applied mode of treatment in patients with an acute coronary syndrome (ACS) or an ST elevation myocardial infarction (STEMI). Platelet activa-tion and subsequent aggregation play a dominant role in the propa-gation of arterial thrombosis and consequently are the key thera-peutic targets in the management of ACS. Antiplatelet therapy should be instituted as early as possible when the diagnosis of non STE-ACS is made in order to reduce the risk of both acute ischaemic complications and recurrent atherothrombotic events. Platelets can be inhibited by three classes of drugs, each of

STEMI/ACS pharmacology 2013which has a distinct mechanism of action. Aspirin (acetylsalicylic acid) targets cyclo-oxygenase (COX-1), inhibiting thromboxane A2 formation and inducing a functional permanent inhibition in platelets. However, additional complementary platelet aggrega-tion pathways must be inhibited to ensure effective treatment and prevention of coronary thrombo-sis. ADP binding to the platelet P2Y12 receptor plays an impor-tant role in platelet activation and aggregation, amplifying the initial platelet response to vascular damage. The antagonists of the P2Y12 receptor are major thera-peutic tools in ACS. The prodrug thienopyridines such as clopido-grel and prasugrel are actively biotransformed into molecules that bind irreversibly to the P2Y12 receptor. A new class of drug is the pyrimidine derivative ticagre-lor, which without biotransforma-tion binds reversibly to the P2Y12 receptor, antagonizing ADP signalling and platelet activation. Prasugrel and ticagrelor are more potent and with more consistent

action than clopidogrel drugs. In the TRITON TIMI 38 and PLATO trials they provided superior than clopidogrel antiischaemic action, though with an increasing number of bleedings. Further-more, i.v. GP IIb/IIIa receptor antagonists (abciximab, eptifiba-tide, and tirofiban) target the final common pathway of platelet aggregation and are useful complementary antiplatelet agent in high risk cases or with high thrombus burden.Apart from antiplatelet treatment i.v. anticoagulant therapy is essen-tial to modify the disease process and its progression to death, MI, or recurrent MI in the majority of patients who have ACS due to thrombosis on a plaque. Unfrac-tionated heparin, low-molecular weight heparins, fondaparinux and bivalirudin represents the four antithrombin categories administered as adjunctive to PCI in patients with ACS/STEMI. The intensity of treatment is tailored to individual risk, and triple-antithrombotic treatment is used in patients with continuing

ischemia or with other high-risk features and in patients oriented to an early invasive strategy.Community incidence rates for STEMI have declined over the past decade, whereas those for non–ST-elevation ACS have increased. However, at present, STEMI comprises approximately 25% to 40% of MI presentations. Primary PCI of the infarct artery is preferred to fibrinolytic therapy when time-to-treatment delays are short and the patient presents to a high-volume, well-equipped center with experienced interven-tional cardiologists and skilled support staff. Adjunctive antiplate-let and anticoagulant treatment is mandatory in order primary PCI to achieve its superior to throm-bolysis results. The new antiplate-let agents, prasugrel and ticagre-lor, are particularly suitable for primary PCI STEMI patients, although a relative delay in their onset of action has been observed in this scenario. The latest i.v. antiplatelet agent cangrelor is a promising choise.

Live with Dr. Raj DaveSmall Theatre Hall @ 13:00

From

LIVE TRANSMISSION FROM C3

Prof. Samir Morcos Rafla. Alexandria Univ. The European Society of Cardiol-ogy (ESC) has issued a consen-sus statement regarding the use of catheter-based renal denerva-tion for the treatment of high blood pressure, stating that the novel therapy can be considered a therapeutic option in patients with drug-resistant hypertension who cannot get to goal with a combination of lifestyle and pharmacologic therapy.The data support the concept that the radiofrequency ablation of the renal nerves reduces blood pressure and improves blood-pressure control in these difficult-to-treat patients. The data support-ing the treatment now extend to 36 monthsMahfoud F, et al. Expert consen-sus document from the European Society of Cardiology on catheter-based renal denervation. Eur Heart J 2013; DOI:10.1093 Patients are eligible for renal denervation if they meet the following criteria:Office-based blood pressure >160 mm Hg (>150 mm Hg in patients with type diabetes).Use of three or more antihyperten-sive drugs in adequate dosage and combination, including use of a diuretic.Have attempted to modify blood pressure with lifestyle changes.Secondary hypertension has been excluded.Pseudoresistance has been excluded with the use of ambula-tory blood-pressure monitoring.Patients have preserved renal function (glomerular filtration rate >45 mL/min/1.732).Absence of polar or accessory arteries, no renal artery stenosis, and no prior renal revasculariza-tion.Treatment involves approximately 4 to 6 applications Using low-power (8 W) radiofrequency energy. Treatments are delivered in a helical fashion within the renal artery by rotation of the

Catheter-Based Renal Sympathetic Denervation in the Management of Resistant Hypertension

catheter and approximately 5 mm pullback between ablations. The generator provides the radiofre-quency energy according to an automated algorithmAttenuation of sympathetic activity may have a multitude of effects beyond those directly related to hypertension. Increased sympathetic nervous system activity, for example, is associated with heightened risk of death among heart failure patients. Further, salt and water retention in some forms of heart failure may be mediated in large part by renal sympathetic activity, and selective renal denervation may play a role in treatment or prevention of heart failure and the cardiorenal syndrome. Recent reports in patients with insulin resistance or type II diabetes mellitus,polycystic ovary syndrome, and hypertension have also suggested improved insulin resistance and glycemic control with denervation therapy.Multielectrode renal-denervation device appears safeVascular lesions induced by renal nerve ablation as assessed by optical coherence tomography: pre- and post-procedural compari-son with the Simplicity(R) catheter system and the EnligHTN™ multi-electrode renal denervation catheter. Eur Heart J Apr 2013; CONCLU-SION: Here we show that diffuse renal artery constriction and local tissue damage at the ablation site with oedema and thrombus forma-tion occur after RNA and that OCT (optical coherent tomography) visualizes vascular lesions not apparent on angiography. This suggests that dual antiplatelet therapy may be required during RNA.

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CardioAlex 2013

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Prevalence of Cardiovascular Risk Factors in General Practice Patients in Africa and the Middle East: the AfME CV Epidemiological ACE Study

7

Prof. Mohamed AlamiAlawi A. Alsheikh-Ali, Iqbal M. Omar, Frederick J. Raal, Wafa Rashed, Omar Hamoui, Abdoul Kane, Mohamed Alami, Paula Abreu, Walid MashhoudBackground: Increased urbaniza-tion in the developing world parallels a rising burden of chronic diseases. Developing countries account for ~ 80% of global cardiovascular (CV) deaths, but contribute a paucity of systematic epidemiological data on CV risk factors (CVRFs). This lack of data is contributing to the increasing burden attributed to cardiovascular diseases which have exceeded infectious diseases. If nothing is done to understand and reverse the situa-tion, cardiovascular disease could become a public health time bomb in developing coun-tries.Objective: To estimate the preva-lence of CVRFs in rural and urban

cohorts attending general prac-tice clinics in the Africa and Middle East (AfME) region.Methods: In a cross-sectional, multi center multi country epide-miological study, we evaluated the presence of CVRFs (hypertension (HTN), diabetes mellitus (DM), dyslipidemia (DL), obesity, smoking and abdominal obesity (AO)) in stable adult outpatients attending general practice primary care clinics. Obesity was defined as Body Mass Index (BMI) >=30kg/m2. AO was defined as waist circumference>=94cm in men and >=80cm in women. HTN was defined as Blood Pressure (BP) >=140/90 mmHg and for diabe-tes patients >=130/80. DM was defined as fasting plasma glucose >=7mmol/l. Smoking refers to current smoking. A rural population was defined as isolated (>50 km or lack of easy access to commuter transporta-tion) from urban centers.Results: We systematically enrolled 4,379 patients from 94 clinics across 14 AfME countries. Mean age was 46 ±14 years and 52% were female. Mean BMI was 28 in men, 30 in women, and 29 in the overall cohort (kg/m2). DL

was present in 70% [68, 71] of the overall cohort. Among patients with dyslipidemia and at low risk, 79% reached the LDL goal (as per NCEP III guidelines). Only 20% of the patients with dyslipidemia and at high risk reached their LDL goal (as per NCEP III guidelines). AO was present in 68% [66, 69] of the cohort. HTN affected 43% [41, 44] of the cohort. DL and AO were widespread affecting ~ 2/3rd of subjects, followed by high rates of HTN and DM. Obesity was present in 37% of the overall cohort. Overweight was present in 35% of the total population. These findings were observed in both genders with higher preva-

lence of obesity and AO in females. Urban and rural centers showed similar risk factor profile.Conclusion: CVRFs are highly prevalent among relatively young, stable patients attending general practice clinics across AfME. The findings support opportunistic screening for CVRFs whenever patients visit a general practitio-ner and provide an opportunity for early identification and man-agement of CVRFs, including lifestyle interventions. At the community level, the high risk profile of this young populationshould convince policy-makers of the need for an effective strategy to prevent cardiovascular diseases in the region.

Renal Denervation – First Egyptian Experience

Hazem Khamis,MD,IntroductionSuccessful treatment of raised blood pressure has proven elusive despite availability of various drugs, combination pharmaceutical products, and resources to assist patients’adherence and lifestyle changes. In about half of hyper-tensive patients, blood pressure remains higher than accepted treatment targets despite broad availability of effective pharma-ceutical agents .Thus, the development of new approaches for the management of hypertension, is a priority. These considerations are especially relevant to patients with drug-resistant hypertension and/or patients with severe intolerance to medication.Renal sympathetic nerves contrib-ute to development and perpetua-tion of hypertension, and sympa-thetic outflow to the kidneys is activated in patients with essen-tial hypertension . Efferent sympa-thetic outflowstimulates renin release, increases tubular sodium reabsorption, and reduces renal blood flow . Afferent signals from the kidney modulate central sympathetic outflow and thereby directly contribute to neurogenichypertension .Radical surgical methods for sympathetic denervation have been successful in lowering blood pressure in severely hyper-tensive patients. However, these methods were associated with high perioperative morbidity and even mortality and also long-term complications .Recently, a percutaneous, catheter-based approach using radiofrequency energy (RF) was developed to disrupt renal sympa-thetic nerves. This resulted in no severe (long-term) vascular or renal injury. Importantly, catheter-based renal nerve ablation was associated with a significant reduction in both systolic and diastolic blood pressure on top of maximal medical therapy, which persisted throughout 12 months follow-up in the first-in-man

study .The Symplicity HTN-2 Trial was recently published, which was the first randomized controlled study using this technique of renal denervation, confirming the findings of the first-in man study .Here, we report the results of the Egyptian experience regarding this novel treatment modality.MethodsStudy design and PatientsPatients were eligible if they have an office systolic blood pressure of 160 mmHg or more, despite being compliant with at least three antihypertensive drugs,or confirmed intolerance to medication. Blood pressure measurements were performed in a seated position in at least two subsequent visits in both arms. Blood pressure check was performedbefore intervention and at 6 months follow-up.Also, renal function and changes in plasma renin level were obtained at baseline and during follow-up.The renal artery anatomy was considered suitable in case of a vessel diameter of ≥4 mm, no prior renal angioplasty/ stenting and no significant stenosis or other abnormalities.Exclusion criteria for this treatment modality were pregnancy, age below 18 years, patients with any known second-ary cause of hypertension and a glomerular filtration rate estimated at <45 mL/min/1.73 m². Also, patients with type 1 diabetes, haemodynamically significant valvulardisease or implantable cardio-verter defibrillators were excluded from intervention.Thirty patients underwent renal denervation and another thirty patients with resistant hyperten-sion were considered as control.ProcedureThe baseline activated clotting time (ACT) was determined, the renal artery was catheterized via standard femoral access, and renal angiography was then performed, after which 70 mg/kg

of heparin sodium was adminis-tered. When an ACT of 250–300 seconds had been achieved, a Symplicity electrode was introduced through a renal double-curve, left internal mam-mary artery, or renal short standard guiding catheter at least 6F in diameter. The radiopaque tip of the electrode was brought into contact with the endothe-lium, initially at the most distal point of the renal trunk.When the impedance was stable we applied RF energy for 2 minutes, automatically regulated to 8Watt with a maximum temperature of 70 C. If theimpedance value recorded at the time of RF application was too high, indicating the presence of calcium, the electrode was moved to a more favorable position. If the bifurcation was early, RF could be applied in the branches, provided they were of adequate diameter (i.e, ≥ 4 mm).A bilateral treatment of the renal arteries was performed with the use of series of 2-minute RF energy deliveries along each artery, aiming at 4–6 treatment points per artery. These treatment points are made with a minimum of 5 mm distance in between and with a pullback from distal to proximal in a circumferential way. A control angiography was performed after the procedure.ResultsThe baseline characteristics of the patient groups are listed in Table 1. The mean time of the procedure (i.e. from puncture of the femoral artery to closure) was 74±9 min. Mean fluoroscopy time

was 14±5 min. The ACT time achieved was 288±44 s. The mean use of contrast was 208±35 ml.).Table 1: Baseline patient charac-teristics: Demographic informa-tionAge, yrs56±6Men, %80 BMI, kg/m2 28.9±3.3 Relevant medical historyDuration of hypertension, yrs9.8±2Diabetes mellitus18(60%)CAD12(40%) Antihypertensive drugsACEI/ARB 28(93.3%)Calcium channel blocker28(93.3%)B-blocker 22(73.3%)Diuretic 30(100%)�-blocker 2(6.7%)Centrally acting drug 0(0%)Values are mean ± SD or n (%).ACEI= angiotensin-converting enzyme inhibitor; CAD = coronary artery disease.In total, an average of 4.9±1 RF ablations was performed in the left renal artery, and 5.2±1 RF ablations in the right renal artery. No patients showed endovascu-lar damage at final angiography.Table 2 mmHg; p=0.001).While in the control group, there was no significant decrease in blood pressure.No significant change was noted in serum creatinine level after the procedure (0.95±0.18 mg/dL before compared with 1.04±0.2 mg/dL after 6 months; p=0.234). However, there was a statistically significant drop in plasma rennin level at 6 months after denerva-tion (from 3.66±0.64 to 3.37±0.47 ng/mL/hour; p=0.003) compared with the control group.

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Management office in charge:Address: El Asdekaa building (2) - Masged El Asdekaa St., Garden City Smouha - Alexandria - EgyptTel./Fax : +203 420 4849 Cellular: +2010 1224849 e-mail: info@icomegypt.com +203 424 9072 info@icomgroup.orgWebsite : www.icomegypt.com

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SymposiumWednesday, 12 June

14:15 - 15:15Hall: Main

ChairpersonsKhalifa Mahmoud

ModeratorMohamed Sobhy

14:15 - 15:00

15:00 - 15:15

Patient at high cardio-metabolicrisk: new therapeutical optionsAlberto Corsini - ItalyCitagliptin :a novel solution forDiabetic patients in RamadanKhalifa Mahmoud - Alexandria

Symposium

Wednesday, 12 June16:15 - 17:15

Hall: Small TheatreChairpersonsAdel El Etriby

Amr ZakiHany Ragy

Hazem KhamisMohamed Sobhy

16:15 - 16:25

16:25 - 16:35

16:35 - 16:4016:40 - 16:50

16:50 - 16:5516:55 - 17:10

17:10 - 17:15

BVS: Introduction to AbsorbEhab El Nady - AbbottBVS: Latest Clinical DataBernard Chevalier - FranceDiscussionBVS: Absorb into real worldOmer Goktekin - TurkeyDiscussionMitraClip Egypt ExperienceHazem Khamis Sixth of OctoberDiscussion

Vascular

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Editor in Cheif:Prof. Mahmoud Hassanein

Visit us and Subscribe at our stand at Level 1

Symposium

Wednesday, 12 June12:00 - 13:00Hall: Main

ChairpersonsAdel El Etriby

Ihab AttiaMohamed SobhyMoustafa NawarSherif El Tobgi

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12:15 - 12:30

12:30 - 12:45

12:45 - 13:00

Cornerstones in ACS Management.Fausto pinto - PortugalARBs and end organ protection.Ashraf Reda - MenoufiaA step towards protection of high riskhypertensive patientsMahmoud Hassanein - AlexandriaDiscussion

Wednesday, 12 June09:30 - 10:30

Hall: Small TheatreChairpersonsAmr ZakiAntoine LafontAshraf RedaHazem El GuindyIhab AttiaJosepa MauriMostafa Youssef

09:30 - 10:30 OperatorsZiyad Ghazzal LebanonSherif Wagdy Ayad - AlexandriaMahmoud Hassanein - Alexandria

First National LiveIN

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The role of clopidogrel in the management of ischemic heart disease David J.David J. Homan and Matthew J. PricePurposePurpose of reviewPlacebo-controlled randomized trials have demonstrated the efficacy of clopidogrel in combina-tion with aspirin across a broad range of clinical presentations. Recent trials have addressed several remainingissues regarding clopidogrel therapy.Recent findings Three random-ized trials examined the role of platelet function testing (PFT) in clopidogrel-treated patients.The results do not support the use of PFT to adjust clopidogrel dose after percutaneous coronary intervention (PCI), particularly in patients with stable angina or ischemia, in whom-event rates are low irrespective of on-treatment reactivity. Doses greater than clopidogrel 150mg daily are required to sufficiently overcome high reactivity in CYP2C19 loss-of-function (LOF) allele carriers. Clopidogrel response variability also influences the time to platelet recovery after drug discontinua-tion, and a proof-of-principle study supports the concept of using PFT for surgical timing. Unlike its efficacy in the setting of acute coronary syndrome (ACS) and PCI, prasugrel was not superior to clopidogrel in medically treated patients recov-ering from ACS.Summary Current data do not support routine PFT to guide antiplatelet therapy in patients undergoing nonurgent PCI.The role of PFT to optimize therapy in ACS patients remains unaddressed, and further study is needed to confirm its promise in guiding surgical timing in patients who have discontinued therapy. Clopidogrel remains an important therapeutic option for patients presenting after an ACS who did not undergo initial revasculariza-tion.Keywords: clopidogrel, CYP219, genotype, platelet function testing, thienopyridineINTRODUCTIONPlacebo-controlled randomized trials have demonstrated the efficacy of clopidogrel therapy, in combination with aspirin, in the setting of percutaneous coronary intervention (PCI) [1,2], non-ST elevation [3], and ST-elevation acute coronary syndrome (ACS) [4,5] and, according to sub-group analysis, for secondary preven-tion in patients with established

GUIDELINE UPDATESThe American College of Cardiol-ogy Foundation (ACCF) /American Heart Association (AHA) and genotyping should utilize larger clopidogrel doses or alternative P2Y12 receptor antagonists in patients with high on-treatment reactivity. Further trials are required to define the clinical efficacy of PFT to time surgical intervention after thienoypridine discontinuation,and to optimize antiplatelet therapy in ACS managed with an early invasive strategy. More intensive P2Y12 receptor inhibi-tion with prasugrel was not superior to clopidogrel in reduc-ing ischemic events in medically treated patients recovering fromACS, but led to more TIMI major and minor bleeding, and there-fore this agent should not be used in this patient population CONCLUSIONRecent clinical trials provide further data regarding the clinical efficacy of clopidogrel in patients

atherothrombotic disease [6]. A number of trials have recently been reported that address several remaining questions regarding clopidogrel therapy for ischemic heart disease, in particu-lar the role of platelet function testing (PFT) and genotyping, the optimal waiting period for surgeryafter drug discontinuation, and the relative efficacy of the more potent thienopyridine prasugrel inpopulations beyond the confines of the ACS patients undergoing PCI studied in TRITON-TIMI (Trial to Assess Improvement in Thera-peutic Outcomes by Optimizing Platelet Inhibition with Prasugrel – Thrombolysis in Myocardial Infarc-tion)- 38 [7]. Herein, we review these data and discuss their clinical implications.CLINICAL TRIALS OF PLATELET FUNCTION TESTINGA large body of data from observa-tional studies support an associa-tion between on-treatment reactivity while receiving clopido-grel and cardiovascular events after PCI [8,9&]. Several recent randomized multicenter trials explored whether the use of pointof- care PFT can improve outcomes in PCI patients GENET-ICS AND CLOPIDOGRELClopidogrel is a prodrug that requires biotransformation by the hepatic CYP450 system into an active metabolite in order to exert its antiplatelet effect.Prior studies have shown that common genetic polymorphisms that reduce the catalytic activityof the CYP2C19 isoenzyme decrease circulating levels of active metabolite, reduce levels of platelet inhibition, and increase the risk of ischemic eventsin clopidogrel-treated patients undergoing PCI [18].A recent randomized trial showed that point-of-care genotyping can identify CYP2C19 2 loss-of-function (LOF) allele carriers and that treatment of carriers with prasugrel can reduce high on-treatment reactivity [19]. Several recent studies have further explored this relationship and provided insight into the potential role of different CLOPI-DOGREL AND SURGERY The 2012 American College of Cardiol-ogy (ACC)/ American Heart Association (AHA) Guidelines recommend empirical discontinu-ation of clopidogrel for at least 5 days before planned coronary artery bypass grafting (CABG), unless the net benefit of the thienopyridine outweighs the

potential risks of excess bleeding [26&&]. Recent studies have explored platelet functional recov-ery after clopidogrel discontinua-tion and the timing of surgery in clopidogrel- treated patients

with ischemic heart disease. Despite their limitations, current trials do not support the use of PFT to optimize clopidogrel dosing in patients undergoingpredominantly nonurgent PCI. Randomized studies have shown that doses greater than clopido-grel 150mg maintenance dose are required to provide a sufficient pharmacodynamic effect in CYP2C19 LOF allele carriers; future studies of PFT or genotyping should utilize larger clopidogrel doses or alternative P2Y12 receptor antagonists in patients with high on-treatment reactivity. Further trials are required to define the clinical efficacy of PFT to time surgical intervention after thienoypridine discontinuation, and to optimize antiplatelet therapy in ACS managed with an early invasive strategy. More intensive P2Y12 receptor inhibition with prasugrelwas not superior to clopidogrel in reducing ischemic events in medically treated patients recov-ering from ACS, but led to more TIMI major and minor bleeding, and therefore this agent should not be used in this patient popula-tion

Table 1. Recommendations pertaining to P2Y 12 antagonists in the 2011 European Society of Cardiologyguidelines for the management of acute coronary syndrome in patients presenting without persistent STelevation [36 && ]

Classi�cation Level of evidence Recommendation

I A A P2Y 12 inhibitor should be added to aspirin as soon as possible and maintained over 12 months,unless there are contraindications such as excessive risk of bleeding.

I B Ticagrelor (180-mg loading dose, 90mg twice daily) is recommended for all patients at moderate-to-high risk o� schemic events (e.g. elevated troponins), regardless o� nitial treatment strategyand including those pretreated with clopidogrel (which should be discontinued when ticagreloris commenced).

I B Prasugrel (60-mg loading dose, 10-mg daily dose) is recommended for P2Y 12 -inhibitor-naivepatients (especially diabetics) in whom coronary anatomy is known and who are proceedingto PCI unless there is a high risk o� ife-threatening bleeding or other contraindications.

I A Clopidogrel (300-mg loading dose, 75-mg daily dose) is recommended for patients who cannotreceive ticagrelor or prasugrel.

I B A 600-mg loading dose of clopidogrel (or a supplementary 300-mg dose at PCI following aninitial 300-mg loading dose) is recommended for patients scheduled for an invasive strategywhen ticagrelor or prasugrel is not an option.

Table 2. Recommendations pertaining to P2Y 12 antagonists in the 2012 European Society of Cardiologyguidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation[35 && ]

Classi�cation Level of evidence Recommendation

I A An ADP-receptor blocker is recommended in addition to aspirin: options are:

I B Prasugrel in clopidogrel-naive patients, if no history of prior stroke/transient ischemic attack,age < 75 years

I B Ticagrelor

I A Clopidogrel, preferably when prasugrel or ticagrelor are either not available or contraindicated

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Summary of Talk ACC highlights 2013 on HF and HTNACC.13 Highlights: Hypertension and Heart Failure.

Dr. Bove is past president of the American College of Cardiology.AA Bove, MD, PhDSTOP-HF. The value of BNP in managing patients with chronic HF. After 7 years, overall outcome (freedom from MACE) was reduced in both control and BNP guided management.ASTRONAUT. Effect of Aliskirin on Mortality and HF readmis-sions. Patients post hospitaliza-tion for acute HF were random-ized to usual care, or usual care plus Aliskirin 300 mg. After 6 months there was no difference in outcome between the Aliskirin treated and the placebo group.RELAX. Effect of PDE-5 Inhibition on clinical outcome in patients with HF with preserved EF.

Patients with HFPEF were randomized to usual care or usual care plus sildenafil 20 mg TID. And evaluated at 24 months. NO differences were found between the Sildenefil group and controls in peak oxygen consumption, or 6 minute walk distance.HYPERTENSION- TELEMEDI-CINE. Evaluation of a telemedi-cine self reporting system using the Internet and mobile phone in anaging chronic hypertension. After 6 month, non-diabetic patients using the telemedicine system demonstrated a greater improvement in BP compared to a usual care control group.POLYPILL for HTN in CHINA. The study was done in 11,312 Chinese hypertensive subjects. Mean blood pressure fell from hypertensive to normotensive values after 8 weeks using a single pill combining Valsartan and amlodipine.MENDELIAN RANDIMIZATION to

PREDICT HYPERTENSION. The study examined patients with systolic BP below 120 at age 40 to those with systolic BP of 130 mmHg at age 40. The subjects with lower BP at age 40 showed a significant reduction in long term risk for developing hypertension and CAD. The genetic score was a stronger predictor of risk for CAD compared to risk evaluated in prospective cohort studies or HTN randomized trials.ACCOMPLISH. Evaluation of treatment effect in patients with different responses to initial HTN therapy. Patients were divided into groups based on BP response to initial HTN treatment. Patients with the greatest reduc-tion of BP after initial therapy demonstrated a reduction in stroke rate compared to other groups studied. However, the MI response was optimal with systolic BP in the 120-130 range and was higher for treatment BP

below and above that range.AGING and BP effects on PULSE WAVE VELOCITY. PWV is a measure of arterial stiffness and is known to increase with age. The study examined the effects of age and BP on longitudinal changes in PWV. Men demon-strated a greater increase in PWV between ages 40 and 90, while women showed a small increase after menopause that stable over 30 years. Longitudinal changes in PWV were correlated with systolic blood pressure.RENAL ARTERY DENERVATION in TREATMENT RESISTANT HYPERTENSION. This study examined effects of renal denerva-tion on moderate TRH with BP > 140/90. Mean Systolic BP was reduced from 151 to 138 mmHg and diastolic BP was reduced from 82 to 75 mmHg over 6 months. Ambulatory systolic BP showed a reduction of 14.1 mmHg over 6 months.

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TREK and MINI-TREK are trademarks of the Abbott Group of Companies.This product is intended for use by or under the direction of a physician. Prior to use, it is important to read the package insert thoroughly for instructions for use, warnings and potential complications associated with the use of this device. Information contained herein is for distribution for Europe, Middle East and Africa ONLY. Please check the regulatory status of the device before distribution in areas where CE marking is not the regulation in force. All drawings are artist’s representations only and should not be considered as an engineering drawing or photograph. Photo(s) on file at Abbott Vascular. For more information, visit our website at www.abbottvascular.com

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