What causes a heart attack without coronary artery blockage?

Heart Attack Without Blockage: Mechanisms and Causes

Heart attacks can occur without significant coronary artery blockage through several distinct mechanisms, most commonly coronary artery spasm, spontaneous coronary artery dissection (SCAD), microvascular dysfunction, and supply-demand mismatch (Type 2 MI). 1

Primary Mechanisms

Coronary Artery Spasm (Vasospastic Angina)

• Intense focal spasm of epicardial coronary arteries can cause complete or near-complete vessel occlusion, resulting in transmural ischemia and myocardial infarction even in the absence of obstructive disease. 1, 2
• Spasm results from hypercontractility of vascular smooth muscle and/or endothelial dysfunction, creating an imbalance between vasodilator factors (prostacyclin, nitric oxide) and vasoconstrictor factors (endothelin, angiotensin II). 1, 2
• Attacks typically occur at rest, particularly from midnight to early morning, due to increased coronary artery tone during these hours. 2, 3
• Cocaine and methamphetamine use are important precipitants through enhanced platelet aggregation and coronary spasm. 1
• Even angiographically normal coronary segments often harbor mural atherosclerosis on intravascular ultrasound, predisposing to localized endothelial dysfunction. 2

Spontaneous Coronary Artery Dissection (SCAD)

• SCAD involves spontaneous formation of an intramural hematoma within the coronary artery wall, with or without an intimal tear, and accounts for 20-35% of acute coronary syndromes in women under 60 years. 4
• Over 90% of SCAD cases occur in women, particularly during the peripartum period or in association with fibromuscular dysplasia (present in up to 72% of SCAD patients). 4
• Precipitating factors include intense emotional stress, physical stressors (intense exercise, Valsalva-type activities, labor and delivery), and hormonal fluctuations. 4
• SCAD should be suspected in any young woman presenting with acute coronary syndrome without traditional cardiovascular risk factors. 4

Microvascular Dysfunction

• Dynamic coronary obstruction can be caused by diffuse microvascular dysfunction due to endothelial dysfunction or abnormal constriction of small intramural resistance vessels. 1
• Microvascular spasm, impaired dilation, and extramural microvascular compression can all cause myocardial ischemia without epicardial obstruction. 1
• Women have a higher proportion of acute coronary syndrome caused by coronary microvascular dysfunction compared to classical plaque rupture. 1

Type 2 Myocardial Infarction (Supply-Demand Mismatch)

• Type 2 MI occurs when myocardial necrosis results from conditions other than coronary plaque instability, creating an imbalance between myocardial oxygen supply and demand. 1, 5
• Precipitating conditions include:
  • Increased oxygen demand: fever, tachycardia, thyrotoxicosis 1
  • Reduced coronary blood flow: hypotension 1
  • Reduced oxygen delivery: anemia, hypoxemia, respiratory failure 1
• Coronary embolism and coronary endothelial dysfunction are additional mechanisms. 1

Other Mechanisms

• Coronary artery dissection (distinct from SCAD) can occur as a cause of acute coronary syndrome, particularly in peripartum women. 1
• Takotsubo (stress) cardiomyopathy mimics myocardial infarction with characteristic apical ballooning, typically occurring in postmenopausal women following emotional or physical stress, with modest troponin elevations and no obstructive coronary disease. 1
• Plaque erosion (rather than rupture) causes a higher proportion of acute coronary syndrome in women compared to men. 1

Clinical Recognition

Key Diagnostic Features

• Patients may present with typical chest pain or atypical symptoms including dyspnea, epigastric pain, shoulder/arm/back pain, fatigue, or weakness—particularly common in women. 1
• Transient ST-segment elevation during chest pain that resolves when symptoms abate, typically responding to nitroglycerin, suggests vasospastic angina. 2
• Circadian variation with attacks occurring in clusters and early morning predominance indicates higher myocardial infarction risk from coronary spasm. 2

Important Pitfalls

• A purely anatomical diagnostic approach using invasive coronary angiography or coronary CT may fail to diagnose microvascular and/or vasospastic angina, leading to false reassurance when no obstructive lesions are identified. 1
• Provocative testing with ergonovine is positive in up to 20% of patients with recent myocardial infarction, suggesting vasospasm as a contributing mechanism. 2
• Cardiovascular magnetic resonance is one of the most helpful investigations in myocardial infarction with non-obstructive coronary arteries (MINOCA), helping differentiate cardiomyopathies, myocarditis, coronary microvascular dysfunction, and Takotsubo cardiomyopathy. 1

Treatment Implications

Vasospastic Angina

• Calcium channel blockers (diltiazem, nifedipine) acting alone or in combination with long-acting nitrates are the cornerstone of treatment and prevent coronary arterial spasm in almost all patients. 1
• Beta-blockers are not only ineffective in suppressing coronary arterial spasm in 82% of patients but aggravate spasm in 41%—they should be avoided. 3
• HMG-CoA reductase inhibitors (statins), tobacco cessation, and atherosclerosis risk factor modification are useful. 1

SCAD

• Conservative management is preferred for stable patients, as revascularization attempts can worsen dissections. 4
• Beta-blockers are strongly recommended for long-term management as they reduce recurrence risk. 4
• Aggressive blood pressure control is essential as hypertension increases recurrence risk. 4

Type 2 MI

• The primary focus is treating the underlying cause of oxygen supply-demand imbalance rather than reperfusion therapy. 5
• Specific interventions include correction of hypotension/hypertension, management of tachyarrhythmias/bradyarrhythmias, treatment of respiratory failure, correction of anemia, and control of heart failure. 5
• Reperfusion therapy is indicated for Type 1 MI but not for Type 2 MI or myocardial injury. 5