Can myocardial infarction (MI) occur without atherosclerosis or complete coronary vessel occlusion?

Can Myocardial Infarction Occur Without Atherosclerosis or Complete Occlusion?

Yes, myocardial infarction can definitively occur both without atherosclerosis and without complete coronary vessel occlusion. This is well-established in current cardiology guidelines and occurs through multiple distinct mechanisms.

MI Without Atherosclerosis

Type 2 Myocardial Infarction (Supply-Demand Mismatch)

Type 2 MI represents myocardial necrosis caused by conditions other than coronary plaque instability, creating an oxygen supply-demand imbalance without requiring atherosclerotic disease. 1

Mechanisms include:

• Coronary artery vasospasm causing complete or near-complete epicardial artery occlusion, even in angiographically normal vessels 2
• Coronary endothelial dysfunction exposing smooth muscle to vasoconstrictors 2
• Increased oxygen demand: tachyarrhythmias, fever, thyrotoxicosis, severe hypertension 1, 2
• Reduced oxygen delivery: hypotension, anemia, respiratory failure, hypoxemia 1, 2
• Coronary embolism from cardiac or systemic sources 1
• Spontaneous coronary artery dissection (SCAD) 2
• Microvascular dysfunction without epicardial disease 2, 3

Clinical Recognition

Coronary vasospasm can cause transmural MI identical to atherosclerotic plaque rupture, with provocative testing positive in up to 20% of recent MI patients. 2 Women have a higher proportion of acute coronary syndrome caused by coronary microvascular dysfunction compared to classical plaque rupture. 2

MI Without Complete Occlusion

Type 1 MI With Non-Obstructive Disease

Type 1 MI (atherosclerotic plaque rupture/erosion) can occur with non-obstructive or even no visible coronary artery disease in 5-20% of cases, particularly in women. 1

The 2025 ACC/AHA guidelines explicitly state that Type 1 MI patients "may have underlying severe CAD but, on occasion, non-obstructive or no CAD may be found at angiography." 1

MINOCA (MI with Non-Obstructive Coronary Arteries)

MINOCA is formally defined as acute MI with no coronary stenosis ≥50% on angiography, occurring in 5-25% of all MI presentations. 1, 4, 5

MINOCA diagnostic criteria require: 1

• Elevated cardiac troponin with rise/fall pattern above 99th percentile
• Clinical evidence of ischemia (symptoms, ECG changes, wall motion abnormalities, or angiographic thrombus)
• Absence of obstructive CAD (<50% stenosis in all major epicardial vessels)
• No alternative diagnosis (excludes myocarditis, Takotsubo, pulmonary embolism)

Mechanisms of MINOCA

Intravascular imaging reveals plaque rupture in nearly 40% of MINOCA patients, demonstrating that significant myocardial injury occurs without angiographically visible obstruction. 6 Additional mechanisms include:

• Plaque disruption with microembolization causing distal vessel occlusion without proximal stenosis 1, 6
• Coronary vasospasm superimposed on non-obstructive disease 2, 6
• Coronary dissection 6
• Branch vessel occlusion not visible on standard angiography 6

NSTEMI Pathophysiology

Patients with NSTEMI typically have partially occluded coronary arteries leading to subendocardial ischemia, while STEMI usually involves complete occlusion causing transmural infarction. 1 This demonstrates that significant MI occurs across a spectrum from partial to complete occlusion.

Prognostic Implications

MINOCA is not benign, with 2% death or reinfarction rates in short-to-mid-term follow-up and confirmed as a cause of death in large autopsy series. 6 The prognosis varies significantly based on the underlying mechanism, making accurate diagnosis essential. 4, 3

Diagnostic Pitfalls

A purely anatomical approach using invasive angiography or coronary CT may fail to diagnose microvascular and/or vasospastic angina, leading to false reassurance when no obstructive lesions are identified. 2

Cardiac MRI is a key diagnostic tool, identifying the underlying cause in up to 87% of MINOCA patients, though 8-25% remain unexplained despite optimal workup. 1 Intravascular ultrasound (IVUS) or optical coherence tomography (OCT) may reveal unrecognized plaque rupture not visible on standard angiography. 1, 6

Treatment Considerations

For Type 2 MI, treat the underlying cause of oxygen supply-demand imbalance rather than pursuing reperfusion therapy. 2 For vasospastic angina, calcium channel blockers (diltiazem, nifedipine) alone or combined with long-acting nitrates prevent coronary spasm in almost all patients. 2

For MINOCA without clear non-ischemic cause, guideline-recommended secondary prevention including antiplatelet and antiatherosclerotic medications should be initiated based on the high likelihood of underlying atherosclerotic mechanisms. 6