Does coronary microvascular dysfunction include slow flow?

Does Coronary Microvascular Dysfunction Include Slow Flow?

Yes, coronary slow flow phenomenon is explicitly recognized as evidence of impaired coronary microvascular function in the diagnostic criteria for microvascular angina, defined as a TIMI frame count >25. 1

Guideline-Based Diagnostic Framework

The 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA guidelines provide definitive criteria for diagnosing coronary microvascular dysfunction (CMD), with coronary slow flow phenomenon specifically listed as one of the diagnostic parameters. 1

Evidence of Impaired Coronary Microvascular Function (Criterion 4)

The guidelines explicitly state that coronary slow flow phenomenon, defined as TIMI frame count >25, constitutes evidence of impaired coronary microvascular function. 1 This is listed alongside other microvascular dysfunction markers including:

• Impaired coronary flow reserve (CFR ≤2.0 to ≤2.5 depending on methodology) 1
• Coronary microvascular spasm (reproduction of symptoms with ischemic ECG changes but no epicardial spasm during acetylcholine testing) 1
• Abnormal coronary microvascular resistance indices (IMR >25) 1

Diagnostic Algorithm for Microvascular Angina

Suspected microvascular angina is diagnosed when symptoms of ischemia are present with no obstructive CAD (<50% diameter reduction or FFR >0.80) plus either objective evidence of myocardial ischemia OR evidence of impaired coronary microvascular function alone. 1

Definitive microvascular angina requires all 4 criteria to be present: 1

1. Symptoms of myocardial ischemia (effort or rest angina, exertional dyspnea)
2. Absence of obstructive CAD
3. Objective evidence of myocardial ischemia
4. Evidence of impaired coronary microvascular function (including slow flow)

European Guidelines Corroboration

The 2024 ESC guidelines for chronic coronary syndromes similarly recognize CMD as characterized by decreased CFR and increased microvascular resistance (IMR, HMR, MRR). 1 These guidelines emphasize that CMD can be due to either structural or functional microvascular dysfunction. 1

Invasive Assessment Parameters

The ESC guidelines specify that a Doppler-derived CFR <2.5 in non-obstructive CAD indicates an abnormal microcirculatory response, corresponding to a thermodilution-derived CFR <2.5. 1 An increased IMR (≥25) indicates microvascular dysfunction. 1

Critical Clinical Caveat: Recent Contradictory Evidence

However, a 2023 study in the Journal of the American Heart Association directly challenges the diagnostic utility of coronary slow flow phenomenon (CSFP) for CMD. 2 This high-quality research using simultaneous coronary pressure and flow velocity measurements found that:

• CSFP (CTFC >27) had poor sensitivity (26.7%) and specificity (65.2%) for CMD 2
• CTFC could not predict CMD on receiver operating characteristics analysis (area under curve 0.41) 2
• CSFP was also not diagnostic of coronary endothelial dysfunction 2

The authors explicitly state that "guidelines supporting the use of CTFC in the diagnosis of CMD should be revisited." 2

Reconciling the Contradiction

Despite this recent evidence questioning CSFP's diagnostic accuracy, the current major society guidelines (2023 AHA/ACC and 2024 ESC) continue to include coronary slow flow phenomenon as a diagnostic criterion for CMD. 1

In clinical practice, coronary slow flow should be considered as one piece of evidence suggesting CMD, but not sufficient alone for diagnosis. The guidelines appropriately require either additional objective evidence of myocardial ischemia or other microvascular dysfunction parameters (impaired CFR, elevated IMR, or microvascular spasm) for definitive diagnosis. 1

Pathophysiological Understanding

Coronary slow flow is associated with delayed filling of terminal coronary vessels in the absence of coronary stenosis, believed to result from endothelial dysfunction, inflammatory response, abnormalities in microvascular reserve function, and subclinical atherosclerosis. 3

CMD encompasses both structural and functional alterations in coronary microvasculature resulting in impaired coronary blood flow and consequent myocardial ischemia without epicardial coronary artery obstruction. 4, 5

Practical Clinical Approach

When evaluating patients with angina and non-obstructive coronary arteries: 1

• Document TIMI frame count during angiography (>25 suggests slow flow)
• Perform comprehensive invasive coronary functional testing with pressure and flow measurements when available
• Measure CFR (abnormal if <2.5) and IMR (abnormal if >25)
• Consider acetylcholine testing to assess for microvascular spasm
• Do not rely on TIMI frame count alone to diagnose CMD given recent contradictory evidence 2

The presence of slow flow should prompt further investigation for CMD rather than serving as a standalone diagnostic criterion, particularly given the 2023 evidence questioning its diagnostic accuracy. 2