26th March 2023, Dr Chee L Khoo
We have always known that revascularisation for coronary artery disease (CAD) improve symptoms (and quality of life) but sadly does not always improve survival. Mounting evidence indicates that non-epicardial coronary causes of angina and ischaemia, including coronary microvascular dysfunction, vasospastic disorders, and derangements of myocardial metabolism, are more prevalent than flow-limiting stenoses, raising concerns that many important causes other than epicardial CAD are neither considered nor probed diagnostically. This represents major paradigm change in the management and forces us to relook at how we manage these patients.
Earlier RCTs have not shown incremental benefit of revascularisation in reducing mortality, MI, and repeated revascularisation when added to GDMT, which included multifaceted pharmacologic secondary prevention and lifestyle intervention. Those studies, however, had limitations, eg, inclusion of low-risk subjects, those with mild to moderate baseline ischemia, use of bare-metal or first-generation drug-eluting stents, and lack of blinding before diagnostic coronary angiography.
In the 2021 ACC/AHA Guideline for Coronary Artery Revascularization (3), evidence was cited on improved survival with revascularisation (CABG or PCI) in a subset of patients with stable IHD (SIHD):
- Multi-vessel CAD with severe left ventricular dysfunction
- Significant left main disease
- Multi-vessel CAD (i.e. all three coronary arteries)
In patients with significant proximal LAD stenosis but normal left ventricular ejection fraction the benefit of revascularisation is uncertain. In patients with normal LVEF and 1-2 vessel stenosis not involving the LAD, revascularisation has not been shown to improve survival.
You would assume that when we either stent or bypass the narrowed coronary arteries, the heart muscles will have a new leash of life. With better coronary blood flow, the myocardium will be happier and hence, less cardiovascular events and perhaps, lower mortality. But it doesn’t always.
Causes of myocardial ischaemia
Not all myocardial infarctions (MI) are the same. Most patients presenting with spontaneous MI tend to have type 1 MI which is characterised by coronary plaque rupture or erosion and then superimposed thrombosis. Type 2 MI, on the other hand, is characterised by an imbalance between myocardial oxygen supply and demand, precipitated by an extracardiac stressor, such as hypertension, tachycardia, or hypotension.
Differentiating between type 1 and type 2 MI is clinically important because the therapeutic focus differs. For patients with type 1 MI, the focus is on aggressive antithrombotic therapy and consideration of urgent coronary angiography and revascularization. For patients with type 2 MI, the focus is on treating the extracardiac stressor precipitating the myocardial oxygen supply and demand imbalance.
Thus, in patients who are at risk of Type 2 MI, clearing the coronary artery stenosis may not improve their survival or re-infarction unless you address the extra-cardiac risk factors. Because atherosclerosis is fundamentally a systemic vascular and inflammatory condition affecting epicardial arteries and coronary microcirculation as well as other vascular beds, appropriate guideline directed medical treatment (GDMT) management of ischemia and atherosclerosis must include lifestyle modification (diet, exercise, tobacco cessation).
Stable angina can be caused by obstructive CAD, coronary vasospasm or cardiac microvascular dysfunction (2). If obstructive CAD have been excluded by CCTA, subsequent testing should include stress perfusion imaging, positron emission tomography, and/or invasive functional coronary angiography if not already done. Subsequent focus should then be on drugs that reduce myocardial oxygen consumption (beta-blockers, calcium-channel blockers, or ivabradine) or optimize myocardial oxygen utilisation (e.g SGLT2 inhibitors with proven CV benefits). Lifestyle modifications and intensive risk factor control (including aggressive lipid management with PCSK9 inhibitors) must be in place.
Because cardiology now has many subspecialties, a narrow interpretation of ischaemia by an interventional cardiologist, for example, may limit subsequent of cardiac investigations and it is easy for the GP to be falsely reassured that all is well because the coronary arteries are “OK”.
In summary, the time has come for a paradigm shift in managing stable CAD patients (1). First, we need to expand our current scientific thinking about the many causes and mechanisms of both angina and myocardial ischaemia and uncouple the narrow association of ischemia with obstructive epicardial disease as the guiding approach to management. Both angina and ischaemia have many causes, but obstructive epicardial disease may or may not be the underlying pathogenetic mechanism. Naturally, many patients will have both causes of myocardial ischaemia.
References:
- Boden WE, Marzilli M, Crea F, et al; Chronic Myocardial Ischemic Syndromes Task Force. Evolving Management Paradigm for Stable Ischemic Heart Disease Patients: JACC Review Topic of the Week. J Am Coll Cardiol. 2023 Feb 7;81(5):505-514. doi: 10.1016/j.jacc.2022.08.814.
- Gulati M, Levy PD, Mukherjee D, Amsterdam E, et al 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Cardiovasc Comput Tomogr. 2022 Jan-Feb;16(1):54-122. doi: 10.1016/j.jcct.2021.11.009.
- Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022 Jan 18;79(2):197-215. doi: 10.1016/j.jacc.2021.09.005. Epub 2021 Dec 9. Erratum in: J Am Coll Cardiol. 2022 Apr 19;79(15):1547.