of systolic compression of the microcirculation, the LV receives blood mainly during diastole (>80% of the left coronary flow occurs in diastole). Tachycardia, in addition to increasing O2 demands, reduces myocardial O2 supply by reducing diastolic time.
As opposed to the LV, the RV is thin and does not compress its microcirculation as much in systole, which explains why its flow is not as affected by systole. Approximately 50% of the right coronary-to-RV flow occurs in systole.
The LV coronary blood flow is directly related to the pressure gradient between DBP and LVEDP (coronary perfusion pressure) and inversely related to the microvascular resistance; the latter depends on myocardial stiffness, and, thus, on LVEDP as well (flow = delta pressure/microvascular resistance). An increase in LVEDP reduces coronary flow, even in the absence of a coronary stenosis.
Since the RV receives significant flow during systole, the coronary blood flow of the RV is partly related to the gradient between SBP and RV systolic pressure, not just DBP and RVEDP.
II. Diagnostic approach
A. Clinical features of typical angina
Typical angina is characterized by three features:
1 Retrosternal or epigastric discomfort; neck/jaw/arm pain.
2 Occurrence with exertion or emotional stress.
3 Quick relief by rest or nitroglycerin (within 30 s – 5 min). A prolonged pain (>20 min), or a delay to relief with rest or nitroglycerin (>5 min) usually implies one of two extremes: acute MI or non-cardiac pain.
Angina is precipitated by walking uphill, in the cold, or after a meal.* Nausea or diaphoresis during pain increases the likelihood of angina. Postprandial angina is often a marker of severe, sometimes multivessel CAD. As opposed to biliary colic or peptic ulcer disease, angina occurs immediately after the meal and is exacerbated by postprandial physical activity. Nocturnal angina may imply severe CAD vs. vasospasm on top of fixed CAD; the increased venous return in the recumbent position increases O2 demands and triggers ischemia in patients with critical, sometimes multivessel, CAD. Rest angina without an exertional component may be seen in patients with significant CAD whose angina is mainly triggered by a vasospastic reduction of O2 supply (although many of the latter patients also have exertional angina). Dyspnea may be an angina equivalent and may indicate extensive CAD with secondary increase in LVEDP during ischemic spells; however, dyspnea is very non-specific compared to chest pain. “Warm-up” angina is angina that starts with the onset of activity and improves with further exertion (e.g., in the morning); it suggests a very severe stenosis, with collaterals that get recruited during exertion and a myocardium that adapts to ischemia (ischemic preconditioning).
Figure 3.1 Clinical probability of CAD.
* Combination of diabetes, smoking, or hyperlipidemia (LDL >160–190 mg/dl), especially when all three are present.17
B. Pre-test clinical probability of significant CAD
The presence of all three features defines typical (definite) angina, while two features define possible angina, and chest pain without any additional feature defines non-anginal chest pain. The combination of (1) angina features, (2) age and sex, and (3) risk factors establishes the probability of CAD (Diamond-Forrester and Duke classifications, combined in Figure 3.1).11-13 Note that typical angina is defined by its relation to exertion, not by a description of “chest heaviness” or arm radiation.
In addition, primary ST-T changes or Q waves on the resting ECG imply a higher probability of CAD and a higher-risk CAD, even out- side unstable angina.13
Only 50% of women with classic angina have CAD (as opposed to ~90% of men). The WISE registry shows that ~40% of women undergoing coronary angiography for suspected myocardial ischemia have CAD; the remaining patients likely have macrovascular spasm or microvascular dysfunction without obstructive CAD. While fewer women have obstructive CAD than men, women without obstructive CAD who continue to have chest pain have a worrisome ~9% risk of death/MI at 4 years.14
C. Pre-test probability of high-risk CAD (multivessel, extensive CAD)
Hubbard et al. identified five clinical parameters that predict severe (three-vessel or left main) CAD, beside age: male sex, typical angina, diabetes, insulin dependency, prior MI by history or ECG.15 A 40-year-old patient with four or more of these parameters, or a 60-year-old patient with three or more of these parameters, has a probability of severe CAD of over 40% (e.g., a 60-year-old diabetic man with typical angina). Such symptomatic patients are appropriately referred directly to coronary angiography or CTA without stress testing, as it is highly unlikely that the latter will be normal and, if normal, it may represent a false negative test.16
Other clinical features are predictive of severe CAD and may justify direct referral to angiography (class I for severe angina):13,17,18
High-probability angina that is severe or frequent (e.g., ≥daily). A severe angina is likely to require revascularization for symptom control regardless of stress test results or extent of CAD, as standalone medical therapy is less effective than PCI for symptom control of class III or IV angina.
HF that is likely ischemic (HF with angina, flash pulmonary edema, or older age/combination of risk factors).
Q waves or primary ST-T abnormalities on the baseline ECG, or regional wall motion abnormalities on echo.
D. Testing modalities (diagnostic and prognostic purposes):
High pre-test probability:Coronary angiography is directly performed if typical exertional angina is severe and requires revascularization.CTA is preferred if typical angina is not severe. It excludes left main disease and allows conservative CAD management, as per ISCHEMIA trial.19As an alternative to CTA in typical angina that is not severe, stress testing may be performed, especially in CKD. Here, stress testing is less useful for diagnostic purposes, as the likelihood of CAD remains high even with a negative test. It is, however, useful for risk stratification: a low-risk result allows conservative management.20
Intermediate pre-test probability: stress testing or CTA is performed for diagnosis and prognosis. CTA is also indicated after a high- or intermediate-risk stress test or a negative stress test yet persistent symptoms. SCOT-Heart trial showed that routine CTA on top of functional testing reduces the 5-year MI risk in patients with chest pain, typical or atypical, compared to functional testing alone, not via more revascularizations but via assessing plaque burden and dictating aggressive risk factor control.21
Low pre-test probability (young patient with atypical angina): stress testing may not need to be performed. Even if the stress test is positive, the probability of CAD increases from <10% up to 20%, i.e., the stress test is likely falsely positive. However, if judged necessary, ECG or echo stress testing may be performed (class IIa). Avoid nuclear
