Transcript New Advances in Cardiology - 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 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
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
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 to find simple genetic polymorphisms that
predict cardiovascular disease development
36 candidate genetic defects involving:
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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
Arg403Gln
Arg453Crs
Arg719Trp
Glu930Lys
Arg249Gln
Leu908Val
Val606Met
Cly256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. 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. 01-3670 May 2001
Ridker PM, et al, N Engl J Med 2000 Mar 23;342(12):836-43
Case – September 1999
Applied for 2,000,000 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
Look at all data from Stress Test
Resting ECG (lead placement different)
Exertional drop in BP has 3X 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 2001
Case – September 1999
Applied for 2,000,000 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
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 Today
3D Ultrasound IVUS Imaging: MGI
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
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
New Cardiac Markers of Heart Attack
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Dufour, D. Robert, M.D. Washington VA Medical Center
Impact of Troponin Use
298 Patients with Chest Pain Admitted to CCU
155 (52%)
MI by WHO criteria
127 (43%)
Ischemia
16 (5%)
Non-Cardiac
100% positive cTnT
44 patients
positive cTnT
83 patients
negative cTnT
(15%)
Death or Mi
in 6 months
6/44 (14%)
Death or MI
in 6 months
3/83 (4%)
Death or MI
in 6 months
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 Surgery
Cheaper, shorter and less painful
Requires fewer blood transfusions
Reduces recovery time
Picture from CardioGenesis 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
Treated with radiation brachytherapy
Brachytherapy
FDA approved for in-stent restenosis
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=32
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 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 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
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 !