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Coronary Slow Flow Is Not Diagnostic of Microvascular Dysfunction in...

Utkarsh Dutta, Aish Sinha, Ozan M. Demir, Howard Ellis, Haseeb Rahman and Divaka Perera. Originally published 24 Dec 2022 https://doi.org/10.1161/JAHA.122.027664 Journal of the American Heart Association. 2023;12:e027664

Abstract

Background

Guidelines recommend that coronary slow flow phenomenon (CSFP), defined as corrected thrombolysis in myocardial infarction frame count (CTFC) >27, can diagnose coronary microvascular dysfunction (CMD) in patients with angina and nonobstructed coronary arteries. CSFP has also historically been regarded as a sign of coronary endothelial dysfunction (CED). We sought to validate the utility of CTFC, as a binary classifier of CSFP and as a continuous variable, to diagnose CMD and CED.

Methods and Results

Patients with angina and nonobstructed coronary arteries had simultaneous coronary pressure and flow velocity measured using a dual sensor‐tipped guidewire during rest, adenosine‐mediated hyperemia, and intracoronary acetylcholine infusion. CMD was defined as the inability to augment coronary blood flow in response to adenosine (coronary flow reserve <2.5) and CED in response to acetylcholine (acetylcholine flow reserve ≤1.5); 152 patients underwent assessment using adenosine, of whom 82 underwent further acetylcholine testing. Forty‐six patients (30%) had CSFP, associated with lower flow velocity and higher microvascular resistance as compared with controls (16.5±6.9 versus 20.2±6.9 cm/s; P=0.001 and 6.26±1.83 versus 5.36±1.83 mm Hg/cm/s; P=0.009, respectively). However, as a diagnostic test, CSFP had poor sensitivity and specificity for both CMD (26.7% and 65.2%) and CED (21.1% and 56.0%). Furthermore, on receiver operating characteristics analyses, CTFC could not predict CMD or CED (area under the curve, 0.41 [95% CI, 0.32%–0.50%] and 0.36 [95% CI, 0.23%–0.49%], respectively).

Conclusions

In patients with angina and nonobstructed coronary arteries, CSFP and CTFC are not diagnostic of CMD or CED. Guidelines supporting the use of CTFC in the diagnosis of CMD should be revisited.

Clinical Perspective

What Is New?

Coronary slow flow on angiography has poor sensitivity and specificity to diagnose microvascular dysfunction in patients with angina and unobstructed coronary arteries.
Corrected thrombolysis in myocardial infarction frame count cannot predict any of the indices of endothelium‐independent and endothelium‐dependent coronary microvascular function.

What Are the Clinical Implications?

Guidelines supporting the use of thrombolysis in myocardial infarction frame count to diagnose coronary microvascular dysfunction should be revisited.
Upcoming angiographic technologies to assess coronary microvascular function warrant similar validation studies before clinical use.

Nonstandard Abbreviations and Acronyms

ANOCA: angina with nonobstructed coronary arteries
AChFR: acetylcholine flow reserve
APV: average peak velocity
CED: coronary endothelial dysfunction
CMD: coronary microvascular dysfunction
CFR: coronary flow reserve
CSFP: coronary slow flow phenomenon
CTFC: corrected TIMI frame count
hMR: hyperemic microvascular resistance

Delayed progression of contrast medium in the absence of a significant epicardial stenosis is a common angiographic finding, observed in roughly 7% of angiograms. It was first proposed as a primary mechanism of angina by Tambe et al in 1972, who suggested that this finding most likely represents elevated microvascular resistance. Subsequent studies coined the term coronary slow flow phenomenon (CSFP) and defined it using the corrected thrombolysis in myocardial infarction frame count (CTFC >27). Though initially proposed to assess antegrade flow and microvascular obstruction in the acute revascularization setting, CTFC more broadly is an angiographic surrogate for coronary blood flow, and its use has now been extrapolated to the evaluation of angina with nonobstructed coronary arteries (ANOCA).

Recommendations by COVADIS (Coronary Vasomotion Disorders International Study) recognize CSFP as evidence of impaired microvascular function, commensurate with a diagnosis of coronary microvascular dysfunction (CMD). Furthermore, CSFP has historically been attributed to coronary endothelial dysfunction (CED), which is known to carry a risk of major adverse cardiac events. Guidewire‐based assessment of coronary reactivity to pharmacological vasodilators (ie, adenosine and acetylcholine) remains the gold standard for diagnosing both CMD and CED in patients with ANOCA. Despite CSFP being the most widely accessible method of assessing microvascular dysfunction within the COVADIS criteria, its diagnostic utility has not been formally evaluated against invasive standards. This study therefore aims to (1) test the null hypothesis that patients with CSFP have similar clinical characteristics and invasive physiology to those without CSFP and (2) evaluate the diagnostic utility of CSFP and CTFC to identify patients with CMD and CED defined by invasive methodology.