Cause:Atherosclerotic heart disease; "microvascular angina" caused by impaired vasodilatation capabilities in all arterioles seen in hypertension patients, causes 10-20% of angina (Nejm 1988;319:1302; 1987;317:1366); rarely amyloidosis (Ann IM 1999;131:838), which looks like microvascular angina becaue angiography normal, progresses to CHF. Chronic, asymptomatic CMV infection may increase rate of progression (Nejm 1996;335:624)

Pathophys:Spasm may occur even when there is no fixed lesion if vessel wall mast cell nests are present (Nejm 1985;313:1138). Unstable angina usually due to a platelet thrombus (unlike red thrombus of MI—Nejm 1992;326:287) or fracture of a plaque at the site (Nejm 1986;315:913). Paradoxical vasoconstriction with stress may occur because plaque prevents normal endothelial cell induction of coronary dilatation (Nejm 1991;325:1551)

80% of ischemic events are asx, hence angina is the tip of the ischemic iceberg (Mod Concepts Cardiovasc Dis 1987;56:2; rv of silent isch w/u and rx—Nejm 1988;318:1038); mental stress is as good an inducer of angina as exercise (Nejm 1988;318:1005)

Sx:Onset with first exercise after rest, more frequently in unfamiliar settings, worse supine, worse outdoors (B. Lown, 1985). Relieved by Valsalva, carotid sinus pressure, and TNG promptly (r/o esophogeal spasm pain; and doubts about its dx helpfulness—Ann IM 2003;139:979, 1036)

Si:S₄; mitral regurgitant murmur during pain

ST depressions of >1 mm especially those lasting >60 min at rest or asx are associated with an MI within 6 mo in 15% of the cases (Nejm 1986;314:1214) even when medically rx'd

MI

r/o esophageal reflux, which can clinically mimic exactly (Ann IM 1992;117:824), but value of dx studies questionable once ischemia is r/o (Ann IM 1996;124:959); carbon-monoxide induction if onset at home in winter (Nejm 1995;322:48); syndrome x: anginal/ischemic-sounding chest pain and ST depressions w normal coronaries usually in women (Nejm 2000;342:829, 885) assoc w demonstrable subendocardial hypoperfusion (Nejm 2002;346:1948), responsive (50%) to imipramine 50 mg po hs (Jama 1995;273:883, Nejm 1994;330:1411, 1993;328:1659, 1706), prognosis is good? (Jama 2005;293:117 vs. Nejm 1977;297:916)

Lab:

Chem:CPK-MB may elevate mildly, but subsequent mortality is increased by any elevation above upper limit of normal (Jama 2000;283:247); troponin T levels elevated >0.06 µgm/L (Nejm 2000;343:1139; 1992;327:146)

Noninv:EKG normal in 50% when asx, 30% when sx (B. Lown, 1985); Wellens' Syndrome (Am Hrt J 1982;103:730): evolving anterior T inversions w/o enzyme or Q-wave changes, assoc w severe LAD lesions

Exercise testing (Nejm 2005;352:2524; 2001;344:1840; ACC/AHA guidelines J Am Coll Cardiol 1997;30:260). Contraindicated in CHF, aortic stenosis, IHSS, unstable angina; can't interpret ST changes in face of LBBB, WPW, digoxin, pacing, resting ST depressions >1 mm, LVH, or lack of changes w submaximal test (<85% maximal pulse achieved). Use 1+ mm ST depressions if downsloping or horizontal at 0.06 sec after J point, or 1.5 mm ST depressions if upsloping at 0.08 sec after J point; or if ST depression at rest, positive if STs depress 2 mm more; severity worse if depressions go from 0.5 mm to >2 mm and start in first 3 min, or last 8 or more minutes (Nejm 1979;301:230), and/or hypotension during ETT. Sensitivity 66% but sens/specif depend on pretest probability (Nejm 1979;300:1350); scoring system predicts 5-yr survival and annual mortality (Nejm 1991;325:849). ST depression not predictive of anatomic site, rarer ST elevations are (Ann IM 1987;106:53). If induce paired PVCs or PVCs are >10% of all beats, 10-yr mortality incr 10% over baseline (Nejm 2000;343:826)

Table 2.1 Common Stress-Testing Procedures for the Evaluation of Chest Pain^*

Test	Protocol	Positive Result	Comments	Estimated Sensitivity (%)	Estimated Specificity (%)
Standard treadmill or bicycle exercise	Patient able to perform adequate amount of physical activity Baseline ECG is normal or near normal (e.g., minimal ST-segment depression) Should not be used if patient has left-bundle-branch block or electronic pacemaker	New horizontal or down-sloping ST-segment depression 1 mm or 2 mm in presence of baseline repolarization abnormality	Blood-pressure response exercise duration, ventricular arrhythmias, Duke treadmill score, and heart rate recovery should also be assessed Functional capacity and Duke treadmill score have significant prognostic value	65–70	70–75
Exercise stress echocardiography	Patient able to perform physical activity Two-dimensional echocardiogram immediately after exercise	One or more new segmental wall-motion abnormalities (hypokinesis, akinesis, or dyskinesis), left ventricular dilation, or both	Useful for abnormal baseline ECG (should not be used if patient has left-bundle-branch block or electronic pacemaker) Technically high-quality echocardiogram is essential	80–85	80–85
Dobutamine stress echocardiography	For Patients unable to exercise adequately with or without abnormal ECG Incremental dobutamine infusion	Inducible segmental left ventricular wall-motion abnormalities, worsening of existing wall-motion abnormalities, or left ventricular dilation	Technically high-quality echocardiogram is essesntial	80–85	85–90
Exercise myocardial perfusion SPECT, with quantitative analysis	For patients able to perform physical activity Should be used when results of baseline ECG preclude assessment of ischemia (eg, nonspecific ST-T changes) Can be used in patients with left-bundle-branch block or electronic pacemaker	Inducible single or multiple perfusion abnormalities; left ventricular dilation	Also can provide information on left ventricular function and wall motion	80–85	85–90
Pharmacologic myocardial perfusion SPECT, with quantitative analysis	For patients unable to exercise adequately Intravenous adenosine or dipyridamole Can be used in patients with left-bundle-branch block or electronically paced rhythm	Provides information similar to that provided by exercise SPECT		80–90	80–90
Electron-beam computed tomography	Calcium score closely correlates with extent of coronary artherosclerosis	If score is >100 consider follow-up stress test	Cannot predict coronary obstructions or detect vulnerable plaque or degree of stenosis Poor specificity	—	—

^*Estimates of sensitivity and specificity are derived from multiple databases and from the chronic stable angina guidelines of the American College of Cardiology and the American Heart Association. The sensitivity, specificity, and predictive accuracy of all noninvasive stress-testing methods are influenced by age, sex, degree of coronary atherosclerosis, and most important, the likelihood of coronary artery disease in the patient being tested. ECG denotes electrocardiogram, and SPECT single-photon-emission computed tomography.

Reproduced with permission from Abrams J. Chronic Stable Angina. New Eng J Med 2005;352:2524. Copyright 2005, Mass Medical Society, all rights reserved

Nuclear (sestamibi and/or thallium) scan at peak exercise compared to resting, about 75% sens/specif (Nejm 2001;344:1840); a better predictor of long-term outcome than ETT or Holter (Jama 1996;277:318, Ann IM 1990;113:575); increased lung uptake predicts poor 5-yr outcome (Nejm 1987;317:1485). Non-exertional testing w dipyridamole (Persantine), dobutamine,arbutamine (Med Let 1998;40:19), or adenosine (Jama 1991;265:633) iv thallium test as good as ETT; theophylline blocks and reverses effect of dipyridamole (Med Let 1991;33:87); used when pt cannot walk on treadmill

Echocardiogram w dobutamine stress (Am J Cardiol 1993;72:605); about same sens/specif as Persantine thallium; done w progressive 5-40 µgm/kg/min dobutamine infusion; can also distinguish whether a reversible perfusion defect is also associated w a reversible contraction abnormality, often an issue w reversible thallium defects next to an old infarct; <1/2 the cost of nuclear stress but dependent on operator experience

Xray:(ACP J Club 2008;148:51) Multislice CT w contrast 80-99% sens, 75-90% specif for significant (>50%) coronary lesions; debatable if appropriate