New Advances in Cardiology

September 2002 – Manila, Philippines

By Dr. Philip Smalley MD FRCPCVice President and Medical Director

RGA International

ObjectivesCoronary disease epidemiologyNew cardiac risk factors and Metabolic X SyndromeUnderwriting abnormal stress testsCI heart attack claims issues with troponin useNew imaging techniquesNew 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

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 relatives less than 55

– Prevalence 2%– Odds ratio 5.4

Least stringent– One or more first

degree relative any age

– Prevalence 57%– Odds ratio 2.7

Silbergerg JS, et al, Am J Epid 1998;147:1133-47

Genetics of Atherosclerosis

Primitive state with conflicting small studies prone to publishing biasUnlikely to find simple genetic polymorphisms that predict cardiovascular disease development36 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 Average Life Span

Arg403Gln Arg453Crs Arg719Trp

28 years

Glu930Lys Arg249Gln

43 years

Leu908Val Val606Met Cly256Glu

62 years

Roberts R, J Am Coll Cardiol 2000 Sep;36(3):661-7

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

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

3 of the following

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

Case – September 1999Applied for 2,000,000 life insuranceStress 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

Look at all data from Stress TestResting ECG (lead placement different)

Exertional drop in BP has 3X CAD riskDuration 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 depressionCareful 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 2001

Case – September 1999Applied for 2,000,000 life insuranceStress 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

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

IntraVascular UltraSound (IVUS)

Cardiology Today3D Ultrasound IVUS Imaging: MGI

Magnetic Resonance Imaging

Coronary resolution not yet adequateAccurate Ejection Fractions

                    

Laino, Charlene - MS NBC News

Case – January 2000Admitted to hospital with 3 hours of central chest painAnterior MI on ECGNormal CKMB but cardiac troponins elevatedTreated with primary angioplastyCatheterization showed proximal LAD 95% stenosis

AndMyocardial Infarction

Unstable Plaque

that ruptures

Causing clot

formation

or

0 6 12 18 24 2 3 4 5 6 7 8 9 10

RE

LATI

VE

CO

NC

EN

TRAT

ION

DaysHours

TIME AFTER INFARCT

Normal

TroponinMyoglobin

CK, ASTLDH

Dufour, D. Robert, M.D. Washington VA Medical Center

New Cardiac Markers of Heart Attack

Impact of Troponin Use

(1 5 % )D e a th o r M iin 6 m on ths

1 0 0 % p o s it ive cT nT

1 5 5 (5 2 % )M I b y W H O c rite ria

6 /4 4 (1 4 % )D e a th o r M Iin 6 m on ths

4 4 pa tie n tsp o s it ive cT nT

3 /8 3 (4 % )D e a th o r M Iin 6 m on ths

8 3 pa tie n tsn e g a tive cT nT

1 2 7 (4 3 % )Ische m ia

1 6 (5 % )N o n -C a rd iac

2 9 8 P a tien ts w ith C h e st P a in A dm itte d to C C U

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

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

Keyhole Cardiac SurgeryCheaper, shorter and less

painfulRequires fewer blood transfusionsReduces recovery time

Picture from CardioGenesis Corporation (formerly Eclipse Surgical Technologies)Mack M.J., JAMA 2001 Feb 7;285(5):568-72

Case – March 2000Patient again presents with unstable anginaCatheterization shows in-stent restenosisTreated with radiation brachytherapy

FDA approved for in-stent restenosis

Brachytherapy

Cardiac Support Devices

Insert Spider silk gene in Goat

Figure from The Toronto Star, Sunday, June 9, 2002, page C1

Transmyocardial Revascularization

Pictures from CardioGenesis Corporation (formerly Eclipse Surgical Technologies)

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

http://bmj.com/cgi/content/full/324/7328/31?lookupType=volpage&vol=324&fp=31&view=short

PharmocogeneticsRecombinant DNA therapy to make pure proteins– insulin, growth hormone, blood clotting

factors, erythropoietin etc.

Tailored drug therapies guided by patients genetic profileAvoid certain class of drugs if patient has genetic susceptibility to side effectBlock the abnormal gene product proteinGive patient a therapeutic gene

Gene Therapy for Heart Disease

Inject the gene for new blood vessel growth into the heartAll patients had improved angina and improved perfusion scans

Losordo DW, et al, Circulation 1998 Dec 22-29;98(25):2800-4Pictures from MedScape – Daily news and feature updates

Stem Cell Research to regenerate tissue and organs

Slide from HSC Dr. Scherer’s presentation given in Madrid sponsored by RGA

SummaryHeart disease mortality is improvingWatch for Metabolic X Syndrome traitsIssues with CI claims with troponinsLook at all Stress Test data – not just ST segmentExciting new experimental therapiesGenetic medicine will help patients and doctors in the near future

Thank you !