1. The Evaluation Of Ischemia

2. Case
A 58 year old woman with diabetes and hypertension presents with symptoms of chronic chest pain. She reports that she can walk about 4 blocks at a moderate pace before developing squeezing chest pain, shortness of breath and diaphoresis that resolves with rest. An EKG in the office is normal.

3. Case What is the best next step?
Give her nitroglycerin sublingual and order a treadmill stress test
Refer for emergent angiography
Order nuclear perfusion imaging
Start ASA, BB, nitrates and monitor symptoms

4. Case
During a treadmill stress test she exercises for 6 minutes and stops for chest discomfort. There are infer-lateral ST depressions and nuclear imaging shows a moderate sized reversible inferior defect and no fixed defects. Which of the following is true?
An angiogram followed by a stent will improve her symptoms
An angiogram follow by a stent with improve her symptoms and prolong her life
The patient should be sent for a CABG
The patients medical therapy is not optimized

5. CAD And Angina: Significant Morbidity and Mortality
Incidence 213/100,000 over 30
Lifetime risk: nearly 50% men, 32% women
13,200,000 with CAD, 6,500,000 with angina
7,200,000 post MI
53% of cardiovascular deaths
About 1 in 5 deaths in Americans
142.5 billion in 2006
11.1 million deaths worldwide by 2020
Libby. Braunwald’s Heart Disease. 8th Ed.

6. Cumulative Risk Of CAD Remains High In Advanced Age
Lloyd-Jones. Lancet, 1999.

7. Angina Chest or surrounding area caused by ischemia
Brought on by exertion
No associated with myocardial necrosis
Variety of discomfort
Heavy, squeezing, pressure numb burning
Location
Substernal, arms, epigastric
Anginal equivalents
Dyspnea, faintness, fatigue
Duration
Better with rest or nitroglycerin

8. Not Angina Pleuritic pain Highly localized pain Reproduced by movement
Duration very long or very short
Pain radiating to the lower extremities
Resolution more than 5-10 minutes after nitrates or rest

9. Features That Decrease The Liklihood Of Chest Pain Being Angina
Panju. JAMA, 1998.

10. Grading Angina Class I: angina with strenuous activity
Class II: Slight limitation of ordinary activity
Class III: Marked limitation of ordinary activity
Class IV: Inability to do any physical activity or angina at rest
Goldman. Circulation, 1981.

11. If It Is Not From The Heart….
Panju. JAMA, 1998.

12. Pathophysiology Regional myocardial ischemia
Inadequate coronary blood flow
Increased myocardial oxygen demand

13. Pathology of Atherosclerosis
Abrams. NEJM, 2005.

14. Factors Influencing Myocardial Oxygen Supply and Demand
Libby. Braunwalds Heart Diseasea. 8th Ed.

15. Cardiovascular Risk Assessment
Very high risk: no further estimation
Established vascular disease
Prior MI = 5-7x risk of recurrent MI
Prior stroke= 2-3x risk of MI
PVD = 4x risk of MI
Diabetes
Chronic kidney disease
Hereditary dislipidemia
Canto. JAMA, 2003.

16. Risk of MI In Diabetics With No History of CAD
Haffner. NEJM, 1998.

17. Why Assess Risk? Required for determination of medical management
More than 90% of CHD events in patients with at least one risk factor

18. Risk Factors Associated With CAD
Yusuf. Lancet, 2004.

19. Framingham Risk Calculator
Predicts risk of MI, CAD death and angina
Low risk <10% risk in 10 years
Intermediate 10-20% risk in 10 years
High risk >20% in 10 years

20. Risk Assessment Tools: Framingham Risk Calculator

21. Other Risk Calculators
SCORE
QRISK/QRISK 2
Reynolds

22. Limitations Of Risk Calculation
Falsely reassure patients with borderline risk factors
Does not consider lifetime risk
Inability to account for effects of current therapy
Variation in severity of first event
Variation by type of vascular disease

23. High Sensitivity CRP: Additive Value?
Most patients with CAD have traditional risk factors
Unclear that CRP adds value in clinical practice to traditional risk factors

24. Evaluation of Anginal Chest Pain
Risk factor assessment
Physical Examination
Resting electrocardiogram

25. Asymptomatic Patients
No need for stress testing

26. Non Invasive Stress Testing In Symptomatic Patients
Not useful for diagnosis of CAD in low risk or high risk patients
Useful if it will alter the planned management strategy

27. Treadmill Stress Testing
Useful in patients who can:
Exercise on the treadmill adequately
Have a interpretable EKG

28. Echo Stress Testing Can be performed with exercise or with dobutamine
Requires adequate echo visualization of the heart

29. Nuclear Stress Testing
Can be performed with exercise vasodilator drugs
Adenosine
Dipyridamole
Nuclear tracer is distributed in areas with normal blood flow
Requires contrast between areas of the heart
False negatives with global ischemia

30. Sensitivity And Specificity Of Stress Testing
Modality
Total Patients
Sensitivity[†]
Specificity[†]
Exercise ECG
24,047
0.68
0.77
Exercise SPECT
5,272
0.88
0.72
Adenosine SPECT
2,137
0.90
0.82
Exercise echocardiography
2,788
0.85
0.81
Dobutamine echocardiography
2,582
0.79
Gibbons. JACC, 2002.

31. High Risk Stress Test Features: Proceed to Angiography
Gibbons. JACC, 2002.

32. Moderate And Low Risk Exercise Testing
Gibbons. JACC, 2002.

33. CT Coronary Angiography
Sensitity 90%
Specificity 50%
Not recommended for clinical use

34. Coronary Angiography
Gold standard for identification of significant CAD
Potential for revascularization
Cannot predict future site of plaque rupture and MI
Indications
Concern for left main or triple vessel disease
Poorly controlled symptoms
Ischemia at a low workload (5-6 mets)
Large or multiple defects or WMA

35. Assessment of Left Ventricular Function
Echocardiography or nuclear study
Necessary for strategizing the approach to management

36. Treat Medical Conditions That Can Worsen Ischemia
Anemia
Weight gain
Thyroid disease
Fever
Infections
Tachycardia
Cocaine

37. Necessary Lifestyle Modification
Diet
Exercise
Work activities
Leisure activities
Avoidance of sudden exertion or isometric exercise
Sexual activity
If equivalent level of activity is well tolerated
Sildenafil cannot be taken with nitrates

38. Hypertension Management
For adults, the risk of CAD double for every increase of 20 mmHg over SBP 115
Predisposes to vascular injury, accelerates CAD, increases myocardial O2 demand and worsens ischemia
Goals of treatment
Less than 140/90 or
Less than 130/80 in DM or CKD

39. Smoking Cessation Decreases MI Risk
Meta analysis of 20 studies
30% reduction in risk of recurrent event in patients who quit smoking
The most effective and least expensive approach
Critchley. JAMA, 2003.

40. Goals Of Medical Management In Stable CAD
Improve mortality and morbidity
Manage symptoms
Improve treadmill performance and time to ST changes
Prevent progression of atherosclerotic disease
Requires adequate dosing and combination approach

41. Aspirin Myocardial infarction reduction of 34-87%
No difference in 81 vs 325 mg dose
Clopidogrel may substitute for aspirin in intolerant patients

42. Nitrates Nitrates Systemic vasodilator -> reduced LV wall stress
Reduced myocardial oxygen demand
Acute or chronic treatment
Tolerance can develop
Improved ex tolerance, time to angina, and ST changes
Chen. Proc Natl Acad Sci, 2002.

43. Beta Blockers Beta receptors Reduction in myocardial oxygen demand
B1: increase HR, contractility, AV conduction
cardioselective
B2: vasodilation and bronchodilation
B3: catecholamine induced thermogenesis
Reduction in myocardial oxygen demand
Heart rate, contractility and wall stress
Improved mortality
Prior MI or heart failure

44. ACE Inhibitors No benefit in the reduction of ischemia
Benefits shown in patients with CAD and normal LV function
Improve endothelial functioning
HOPE Trial and EUROPA
20-22% RR ischemic event
HOPE Investigators. NEJM, 2000.

45. Cholesterol Lowering Improves Mortality
NCEP. NHLBI, 2003.

46. Number Needed To Treat Is Low
NCEP. NHLBI, 2003.

47. LDL Target Based On Presence of Risk Factors

48. After Reaching LDL Goals, Target Non-HDL Cholesterol, Then HDL
Total cholesterol – HDL= LDL + VLDL
30 mg/dl higher than LDL goal
Treatment
Statin followed by niacin or fibrates
Low HDL: <40
Lifestyle modification
Niacin or fibrates

49. Ranolazine: Novel Antianginal
No significant changes in heart rate or blood pressure
Reduction in calcium overload via inhibition of the late Na current
Improved exercise performance and time to ischemia
Slight prolongation of the the QT interval, but no association with TDP
Contraindicated in pre-existing QT prolongation

50. Revascularization CABG or PCI
No evidence for mortality reduction in patients with stable angina and normal LV function

51. Courage Trial: Initial Medical Management vs PCI
Unclear benefit of PCI in stable CAD
Inclusion criteria
At least one70% proximal stenosis, and objective ischemia
At least one 80% stenosis and classic angina
Exclusion criteria
Persistent CCS class IV angina
Markedly positive stress test
Refractory heart failure or cardiogenic shock
EF < 30%
Revascularization within 6 months
Anatomy unfavorable to PCI
Randomized 1149-> PCI, 1138-> medical management
Endpoints
Death and nonfatal MI
Death, MI, stroke or unstable angina

52. Courage Trial: No Difference Between Initial PCI And Medical Management
In patients with stable coronary artery disease, it remains unclear whether an initial
management strategy of percutaneous coronary intervention (PCI) with intensive
pharmacologic therapy and lifestyle intervention (optimal medical therapy) is superior
to optimal medical therapy alone in reducing the risk of cardiovascular events.
Methods
We conducted a randomized trial involving 2287 patients who had objective evidence
of myocardial ischemia and significant coronary artery disease at 50 U.S. and Canadian
centers. Between 1999 and 2004, we assigned 1149 patients to undergo PCI with
optimal medical therapy (PCI group) and 1138 to receive optimal medical therapy alone
(medical-therapy group). The primary outcome was death from any cause and nonfatal
myocardial infarction during a follow-up period of 2.5 to 7.0 years (median, 4.6).
Results
There were 211 primary events in the PCI group and 202 events in the medicaltherapy
group. The 4.6-year cumulative primary-event rates were 19.0% in the PCI
group and 18.5% in the medical-therapy group (hazard ratio for the PCI group,
1.05; 95% confidence interval [CI], 0.87 to 1.27; P = 0.62). There were no significant
differences between the PCI group and the medical-therapy group in the composite
of death, myocardial infarction, and stroke (20.0% vs. 19.5%; hazard ratio, 1.05;
95% CI, 0.87 to 1.27; P = 0.62); hospitalization for acute coronary syndrome (12.4% vs.
11.8%; hazard ratio, 1.07; 95% CI, 0.84 to 1.37; P = 0.56); or myocardial infarction
(13.2% vs. 12.3%; hazard ratio, 1.13; 95% CI, 0.89 to 1.43; P = 0.33).
Conclusions
As an initial management strategy in patients with stable coronary artery disease,
PCI did not reduce the risk of death, myocardial infarction, or other major cardiovascular
events when added to optimal medical therapy. (ClinicalTrials.gov number,
NCT )
Boden. NEJM, 2007.