Practical Cardiovascular Medicine. Elias B. Hanna

      Unlike SPECT imaging which qualitatively compares signal intensity of myocardial territories, PET perfusion imaging can accurately quantify myocardial blood flow, using the linear relationship between myocardial blood flow and the speed of radioisotope signal uptake during dynamic imaging. Cardiac MRI can assess myocardial perfusion based on the myocardial signal intensity of gadolinium upon first pass imaging (not late gadolinium imaging); perfusion reserve is reflected by the change of this signal intensity with adenosine. Both modalities can calculate CFR non-invasively.

Appendix 6. Myocardial bridging

      The coronary arteries normally take an epicardial course over the surface of the heart, but they occasionally have an intramyocardial segment that may get compressed in systole and cause symptomatic ischemia. This is called “myocardial bridging,” and it is characterized by angiographic off-and-on narrowing of the intramyocardial segment by >70%, only during systole (milking effect). This phasic obstruction distinguishes bridging from spasm, which is present throughout the cardiac cycle. Bridging is seen in 2% of coronary angiograms and is almost always limited to the LAD. Intramyocardial coronary segments are even more commonly diagnosed on coronary CT, with a frequency of up to 25%.¹⁴⁰

      Since over 80% of the left coronary blood flow occurs during diastole, bridging does not usually cause ischemia and often does not explain chest pain.¹⁴¹ During tachycardia, systolic coronary flow gains more importance as systole occupies a larger part of the cardiac cycle, while stronger inotropism leads to a stronger squeeze of the bridged LAD with a spillover into diastole, which may lead to exertional ischemia. This explains that up to 20% of patients with bridging may have ischemia on stress testing.¹⁴² The combination of exertional angina, ischemia on stress testing, and bridging on angiography without obstructive CAD suggests the diagnosis of symptomatic myocardial bridging. Ischemia correlates with the severity of the narrowing and the intramyocardial depth of the bridge.

      The hemodynamic significance of bridging may be assessed via a modified FFR, where dobutamine is used as the stressor (to exaggerate bridging severity), and the distal-to-proximal pressure ratio is calculated in diastole while ignoring systolic pressures (systolic pressure may falsely overshoot past the bridge, because of the direct compression effect). Non-invasively, stress echo may be used: a significant bridge often leads to a unique pattern of isolated mid-septal buckling which spares the apex; unlike fixed LAD stenosis, a bridge results in ischemia that is mostly localized at the bridge level rather than distal to it.

Even when symptomatic, myocardial bridging is a benign condition with a very low risk of MI or arrhythmia,¹⁴³ yet the abnormal stress may cause atheroma 20-30 mm proximal to the bridge. Nitrates and diuretics aggravate bridging as they lead to reflex tachycardia and increased inotropism; the patient may improve enough upon their withdrawal. In fact, NTG administration is a useful diagnostic test during angiography, as it unveils the severity of bridging (opposite effect on vasospasm). β-Blockers are the mainstay of therapy.

Appendix 7. Coronary collaterals, chronic total occlusion

      In a patient with a coronary total occlusion, the presence of coronary collaterals does not imply that the occlusion is chronic. Underdeveloped intercoronary channels often pre-exist in normal individuals before the occurrence of the coronary occlusion; coronary occlusion or severe stenosis leads to widening of these channels within the first 24 hours, followed by progressive enlargement and maturation of the collateral wall. Mature collaterals that approximate the size of a side branch and provide grade 3 filling of the recipient artery require ≥2 weeks to form, often ≥12 weeks.^144,145

      Basic collateral filling may be seen in acute MI. In fact, half of patients with acute MI develop collateral flow in the first 6 hours, while all patients develop collaterals within 24 hours.¹⁴⁵ More mature collaterals may be seen early in MI if it was preceded by a chronic, severe coronary stenosis (e.g., ≥90% chronic stenosis). Grade 3 collaterals suggest an occlusion that is at least several weeks old, but do not rule out the possibility of acute occlusion on top of a chronic, subtotally occlusive stenosis. Intercoronary collaterals are angiographically graded as follows (Rentrop classification): grade 1 = side branch filling of the recipient occluded artery, without visualization of the body of the recipient artery; grade 2 = partial, faint filling of the body of the recipient artery; and grade 3 (mature collaterals) = complete filling of the recipient artery or presence of a large, continuous collateral the size of a side branch. Nitric oxide promotes collateral growth; traditional risk factors, particularly diabetes, may impede the development of collaterals.

      Mature collateral flow may provide up to 50% of the native antegrade flow, and thus may drastically reduce ischemia.¹⁴⁶ Chronic total occlusions (CTOs) most often develop slowly, allowing collaterals to develop and allowing normal function of the subtended myocardium at rest. While a CTO is almost always associated with stress-induced ischemia, the degree of ischemia depends on the size of the territory and the maturity of collaterals.¹⁴⁷

      CTO is defined as a total occlusion that is >3 months old without any antegrade filling (true CTO), or with faint antegrade filling through microchannels (functional CTO). CTO is distinguished from an acute or recent occlusion by the clinical presentation and the ECG (stable angina in CTO, recent ACS or MI in recent occlusion). A small subset of CTOs may be the long-term remnant of an old, non-recanalized MI. The duration of the CTO is gauged by the date of worsening of angina or the date of an old MI. Bridging collaterals, which are fine collateral vessels that form a caput medusae around the CTO, usually imply an old occlusion >3 months old and a reduced PCI success rate. This fine bridging network is sometimes confused with intra-CTO microchannels (functional CTO), yet the two entities have radically opposite implications: the former implies a low PCI success rate, while the latter implies a high PCI success rate.

      After successful PCI of a CTO, a considerable fraction (50%) of the collateral function is immediately lost through spasm and is non-recruitable should acute reocclusion occur.¹⁴⁵ The patient may have a stable CTO for years; however, if a CTO is recanalized with PCI then acutely reoccludes, an acute MI will ensue, even if reocclusion occurs as early as a few hours or days after recanalization. This is due to: (i) early loss of collateral flow (spasm early on, anatomic involution later on), (ii) distal embolization from the upstream thrombosis, which occludes the microcirculation and any patent collaterals (similar to early SVG thrombosis). Yet sometimes, when reocclusion occurs early, collateral flow may be quickly recruited and may limit MI size.

Appendix 8. Hibernation, stunning, ischemic preconditioning

      Hibernation is chronic impairment of the myocardial function that results from a severe, persistent coronary stenosis; the myocardium downregulates its function and its metabolism to survive and remains viable. Chronic ischemia may, however, lead to irreversible fibrosis. The myocardial segment has reduced nuclear uptake at rest and with stress, but unlike infarction, this nuclear uptake remains >50% at rest, metabolic uptake is preserved on PET imaging, and Q waves are absent.

      Stunning is transient myocardial dysfunction occurring after a severe, transient episode of ischemia. Ischemia resolves and leaves a viable myocardium that will recover in time. This is the case of an acutely occluded MI artery that is opened with PCI or fibrinolytics, exertional ischemia that occurs at stress and resolves at rest, or ischemia induced by cardiac surgery or PCI. Some myocardium is necrotic already, some is stunned; only time will show. As opposed to hibernation, the artery is now open and there is no persistent ischemia. In the post-MI and post-cardiac surgery cases, temporary support with inotropes or IABP is sometimes needed until the myocardium recovers, provided there is no ongoing ischemia. Unlike hibernation, the artery is open and nuclear uptake is usually normal at rest. Repetitive stunning from a significant stenosis (exertional ischemia) can lead to persistent dysfunction and hibernation.

      Recovery of function occurs 1–6 months after revascularization (faster with stunning, days to 1 month). See