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New Advances in Cardiology September 2002 – Manila, Philippines By Dr. Philip Smalley MD New Advances in Cardiology September 2002 – Manila, Philippines By Dr. Philip Smalley MD FRCPC Vice President and Medical Director RGA International

Objectives Coronary disease epidemiology New cardiac risk factors and Metabolic X Syndrome Underwriting abnormal Objectives Coronary disease epidemiology New cardiac risk factors and Metabolic X Syndrome Underwriting abnormal stress tests CI heart attack claims issues with troponin use New imaging techniques New therapies for heart disease

British Heart Foundation Health Promotion Group, University of Oxford, London, 1998 British Heart Foundation Health Promotion Group, University of Oxford, London, 1998

British Heart Foundation Health Promotion Group, University of Oxford, London, 1998 British Heart Foundation Health Promotion Group, University of Oxford, London, 1998

Reasons for CHD Improvements · 1985 to 1993, Hunter Region of New South Wales, Reasons for CHD Improvements · 1985 to 1993, Hunter Region of New South Wales, Australia · Heart disease event rate reduction ( 3. 3%/yr in males and 4. 1%/yr in females) ALL explained by reductions in smoking, blood pressure, cholesterol, and ASA use Dobson AJ et al, J Clin Epidemiol 1999 Aug; 52(8): 761 -71

Family History Risk in Heart Disease Most stringent – 2 or more first degree Family History Risk in Heart Disease Most stringent – 2 or more first degree relatives less than 55 – Prevalence 2% – Odds ratio 5. 4 Silbergerg JS, et al, Am J Epid 1998; 147: 1133 -47 Least stringent – One or more first degree relative any age – Prevalence 57% – Odds ratio 2. 7

Genetics of Atherosclerosis Primitive state with conflicting small studies prone to publishing bias Unlikely Genetics of Atherosclerosis Primitive state with conflicting small studies prone to publishing bias Unlikely to find simple genetic polymorphisms that predict cardiovascular disease development 36 candidate genetic defects involving: – – – Lipid metabolism Coagulation cascade Smooth-muscle proliferation and vascular growth Inflammatory phenomena in the arterial wall Oxidative balance in the vasculature

Prognosis of Cardiomyopathy Mutation Arg 403 Gln Arg 453 Crs Arg 719 Trp Glu Prognosis of Cardiomyopathy Mutation Arg 403 Gln Arg 453 Crs Arg 719 Trp Glu 930 Lys Arg 249 Gln Leu 908 Val 606 Met Cly 256 Glu Roberts R, J Am Coll Cardiol 2000 Sep; 36(3): 661 -7 Average Life Span 28 years 43 years 62 years

New NCEP ATP III Cholesterol Treatment Recommendations National Cholesterol Education Program, NIH Publication No. New NCEP ATP III Cholesterol Treatment Recommendations National Cholesterol Education Program, NIH Publication No. 01 -3670 May 2001

National Cholesterol Education Program, NIH Publication No. 01 -3670 May 2001 National Cholesterol Education Program, NIH Publication No. 01 -3670 May 2001

3 of the following Table from National Cholesterol Education Program, NIH Publication No. 01 3 of the following Table from National Cholesterol Education Program, NIH Publication No. 01 -3670 May 2001

Ridker PM, et al, N Engl J Med 2000 Mar 23; 342(12): 836 -43 Ridker PM, et al, N Engl J Med 2000 Mar 23; 342(12): 836 -43

Case – September 1999 Applied for 2, 000 life insurance Stress test – 5 Case – September 1999 Applied for 2, 000 life insurance Stress test – 5 minutes Bruce Protocol – Peak heart rate of 150 and 144 at 1 minute recovery – Blood pressure response 140/80 rest to 130/70 at peak – 1. 5 mm horizontal ST depression – Pale and dyspneic High calcium score on Electron Beam CT

Exercise Stress Test Exercise Stress Test

Look at all data from Stress Test Resting ECG (lead placement different) Exertional drop Look at all data from Stress Test Resting ECG (lead placement different) Exertional drop in BP has 3 X CAD risk Duration of exercise (good if > 9 min) Timing of ST depression (worse if early and still significant if only in recovery) Symptoms or arrhythmia reported? Heart Rate Response? (worse if less than 12 beats recovery at 1 minute *) Degree and slope of ST depression Careful with computer average tracings * Cole CR et al, NEJM 1999; 341(18): 1351

False Positive Computer Tracing Figure from Dr. Michael Baird, presented at AAIM meeting, Oct False Positive Computer Tracing Figure from Dr. Michael Baird, presented at AAIM meeting, Oct 2001

Case – September 1999 Applied for 2, 000 life insurance Stress test – 5 Case – September 1999 Applied for 2, 000 life insurance Stress test – 5 minutes Bruce Protocol – Peak heart rate of 150 and 144 at 1 minute recovery – Blood pressure response 140/80 rest to 130/70 at peak – 1. 5 mm horizontal ST depression – Pale and dyspneic High calcium score on Electron Beam CT

Electron Beam CT Achenbach S, et al, NEJM, 1998 Dec 31; 339(27): 1964 -71 Electron Beam CT Achenbach S, et al, NEJM, 1998 Dec 31; 339(27): 1964 -71

Prognostic Value of EBCT in Asymptomatic Subjects Figure from O'Malley PG et al, Am Prognostic Value of EBCT in Asymptomatic Subjects Figure from O'Malley PG et al, Am J Cardiol 2000 Apr 15; 85(8): 945 -8 Increased risk of a of nonfatal MI or death or CABG if the calcium score was above a median score

Intra. Vascular Ultra. Sound (IVUS) Cardiology Today 3 D Ultrasound IVUS Imaging: MGI Intra. Vascular Ultra. Sound (IVUS) Cardiology Today 3 D Ultrasound IVUS Imaging: MGI

Magnetic Resonance Imaging § Coronary resolution not yet adequate §Accurate Ejection Fractions Laino, Charlene Magnetic Resonance Imaging § Coronary resolution not yet adequate §Accurate Ejection Fractions Laino, Charlene - MS NBC News

Case – January 2000 Admitted to hospital with 3 hours of central chest pain Case – January 2000 Admitted to hospital with 3 hours of central chest pain Anterior MI on ECG Normal CKMB but cardiac troponins elevated Treated with primary angioplasty Catheterization showed proximal LAD 95% stenosis

Causing clot formation Unstable Plaque that ruptures And Myocardial Infarction or Causing clot formation Unstable Plaque that ruptures And Myocardial Infarction or

New Cardiac Markers of Heart Attack Dufour, D. Robert, M. D. Washington VA Medical New Cardiac Markers of Heart Attack Dufour, D. Robert, M. D. Washington VA Medical Center

Impact of Troponin Use Ravkilde J, et al Scand J Clin Lab Invest 1993 Impact of Troponin Use Ravkilde J, et al Scand J Clin Lab Invest 1993 Nov; 53(7): 677 -85

Cumulative Probability of Death from Cardiac Causes in Relation to Maximal Troponin T Levels Cumulative Probability of Death from Cardiac Causes in Relation to Maximal Troponin T Levels Lindahl, B et al, NEJM Oct 19, 2000 Vol 343, No. 16: pg 1139 -48

Angioplasty and Stents Hall-Garcia Cardiology Associates - Peripheral Vascular Disease: Diagnostic & Treatment Procedures Angioplasty and Stents Hall-Garcia Cardiology Associates - Peripheral Vascular Disease: Diagnostic & Treatment Procedures

Keyhole Cardiac Surgery Cheaper, shorter and less painful Requires fewer blood transfusions Reduces recovery Keyhole Cardiac Surgery Cheaper, shorter and less painful Requires fewer blood transfusions Reduces recovery time Picture from Cardio. Genesis Corporation (formerly Eclipse Surgical Technologies) Mack M. J. , JAMA 2001 Feb 7; 285(5): 568 -72

Case – March 2000 Patient again presents with unstable angina Catheterization shows in-stent restenosis Case – March 2000 Patient again presents with unstable angina Catheterization shows in-stent restenosis Treated with radiation brachytherapy

Brachytherapy FDA approved for in-stent restenosis Brachytherapy FDA approved for in-stent restenosis

Cardiac Support Devices Cardiac Support Devices

Insert Spider silk gene in Goat Figure from The Toronto Star, Sunday, June 9, Insert Spider silk gene in Goat Figure from The Toronto Star, Sunday, June 9, 2002, page C 1

Transmyocardial Revascularization Pictures from Cardio. Genesis Corporation (formerly Eclipse Surgical Technologies) Transmyocardial Revascularization Pictures from Cardio. Genesis Corporation (formerly Eclipse Surgical Technologies)

Rowland, Rhonda, September 14, 2001 Posted: 11: 08 AM EDT (1508 GMT) Penn State Rowland, Rhonda, September 14, 2001 Posted: 11: 08 AM EDT (1508 GMT) Penn State Milton S. Hershey Medical Center College of Medicine

Robotic Surgery Picture from Mack M. J. , JAMA. 2001; 285: 568 -572 Robotic Surgery Picture from Mack M. J. , JAMA. 2001; 285: 568 -572

http: //bmj. com/cgi/content/full/324/7328/31? lookup. Type=volpage&vol=3 http: //bmj. com/cgi/content/full/324/7328/31? lookup. Type=volpage&vol=3

Pharmocogenetics Recombinant DNA therapy to make pure proteins – insulin, growth hormone, blood clotting Pharmocogenetics Recombinant DNA therapy to make pure proteins – insulin, growth hormone, blood clotting factors, erythropoietin etc. Tailored drug therapies guided by patients genetic profile Avoid certain class of drugs if patient has genetic susceptibility to side effect Block the abnormal gene product protein Give patient a therapeutic gene

Gene Therapy for Heart Disease Inject the gene for new blood vessel growth into Gene Therapy for Heart Disease Inject the gene for new blood vessel growth into the heart All patients had improved angina and improved perfusion scans Losordo DW, et al, Circulation 1998 Dec 22 -29; 98(25): 2800 -4 Pictures from Med. Scape – Daily news and feature updates

Stem Cell Research to regenerate tissue and organs Slide from HSC Dr. Scherer’s presentation Stem Cell Research to regenerate tissue and organs Slide from HSC Dr. Scherer’s presentation given in Madrid sponsored by RGA

Summary Heart disease mortality is improving Watch for Metabolic X Syndrome traits Issues with Summary Heart disease mortality is improving Watch for Metabolic X Syndrome traits Issues with CI claims with troponins Look at all Stress Test data – not just ST segment Exciting new experimental therapies Genetic medicine will help patients and doctors in the near future

Thank you ! Thank you !