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November 26, 2021

Can high-resolution cardiac magnetic resonance (CMR) imaging techniques be used for the identification of coronary microvascular dysfunction (CMD)? That’s what researchers from the British Heart Foundation Centre of Excellence and King’s College London set out to determine, exploring whether quantitative perfusion techniques provide greater accuracy than visual analysis.

The study looks at whether high-resolution CMR has the ability to identify CMD in patients with angina and nonobstructive coronary artery disease (NOCAD). By taking intracoronary pressure and flow measurements during rest and vasodilator-mediated hyperemia, and performing CMR (3-T) by visual and quantitative techniques, the researchers aimed to validate non-invasive tests such as CMR and computed tomography coronary angiography (CCTA) as first line diagnostic tools for CMD.

Accurate diagnosis of CMD ‘more paramount than ever’

Patients with angina and NOCAD now account for nearly 50% of those undergoing invasive angiography, and within this group, those with CMD are at a greater risk of major adverse cardiovascular events. Mindful of emerging evidence that “CMD represents a modifiable therapeutic target”, the study highlights that accurate diagnosis of the condition has become more important than ever, but that current diagnostic pathways include invasive methods of angiography.

The promise of CMR in CMD detection

Building on the recent potential CMR has shown in CMD detection among stable angina populations using semi-quantitative analysis of hyperemic myocardial blood flow, the study hypothesized that quantitative analysis of high-resolution perfusion images offers greater accuracy in the identification of CMD than solely visual assessment. The researchers also examined quantitative perfusion techniques to evaluate whether both hyperemic and rest images are needed or if the assessment of hyperemic images alone is sufficient.

Study population and measurement methods

The study enrolled patients undergoing elective diagnostic angiography for investigation of angina pectoris. Inclusion criteria were preserved left ventricular systolic function (ejection fraction >50%) and unobstructed coronary arteries (<30% diameter stenosis or fractional flow reserve >0.80). Exclusion criteria included chronic kidney disease, intolerance to adenosine, and concomitant valve disease.

Catheterization was performed using standard coronary catheters via the right radial artery. Distal coronary pressure and average peak flow velocity were measured using a dual pressure and Doppler sensor-tipped 0.014-inch intracoronary wire. Hemodynamic measurements were taken under resting conditions and during intravenous adenosine-mediated hyperemia (140 μg/kg/min). A dedicated 3-T CMR scanner was used for all scans.

Recruited patients in two groups

Researchers recruited a total of 75 patients for the study. A group of 45 was classified as CMD, with the other 30 patients being a reference group with normal invasive CFR. A higher share of CMD patients was chosen as this group was more likely to have cardiovascular risk factors and refractory symptoms that warrant angiography.

Quantitative perfusion techniques superior to visual analysis

Quantitative perfusion indices including MPRENDO (AUC: 0.90) and MPR (AUC: 0.88) were found to be superior to visual analysis (both p < 0.001). Stress Endo/Epi numerically performed better (AUC: 0.79; p < 0.001) and nearly reached statistical significance in a direct comparison with visual analysis (p = 0.06). Stress MBF performed similarly to visual assessment (AUC: 0.64 vs. 0.60; p = 0.69).

Quantitative perfusion techniques demonstrated a higher accuracy than visual assessment for identifying the CMD presence correctly. When only hyperemic images are obtained, it was found that transmural blood flow distribution (stress Endo/Epi) yielded greater accuracy for identifying CMD. Of the quantitative techniques with excellent sensitivity, the change in subendocardial perfusion from rest during vasodilator-mediated hyperemia performed the best. The researchers suggested that this demonstrates “the importance of acquiring both rest and hyperemic perfusion images and incorporating high spatial resolution imaging and quantitative techniques”.

Importance of rest perfusion image acquisition

In light of the recent discovery of nitric dysregulation underlying resting perfusion abnormalities and pathophysiology consistent with a CMD diagnosis, the study’s data has demonstrated the importance of rest perfusion image acquisition to accurately identify all CMD endotypes. The study has also found that abnormalities in resting flow is a frequent pathological finding in patients with CMD confirmed on invasive testing. Previous studies had indicated that resting flow was similar between groups of patients with CMD risk factors and healthy control subjects.

A powerful gatekeeper to identifying CMD

Optimized use of healthcare resources is presented with a challenge by the risk-stratification of those who have an ischemic substrate of chest pain, because risk factors and typicality of symptoms do not necessitate the presence of CMD. An angiographic diagnosis of NOCAD can be stratified using pressure and flow wire-based measurements, but invasive techniques such as these are still associated with a small risk of complications and higher initial resource cost.

With this in mind, the study has underlined that “high-resolution perfusion CMR with quantitative analysis represents a powerful gatekeeper to identifying CMD in patients with refractory symptoms despite normal coronary computed tomography angiography, potentially circumventing the need for invasive testing in several patients”. The approach is described as a “patient-centric pathway” that minimizes patients’ invasive burden and maximizes diagnostic yield.

Robust full automation of quantitative analysis

The former limitations of quantitative perfusion cardiac MRIs – namely, the time required for post-processing to produce detailed perfusion maps – are being compensated for by recent technical advances that now permit robust full automation of quantitative analysis. According to the researchers: “This is likely to become the method of choice in the years to come on the basis of high diagnostic accuracy, strong prognostic value, and independence from operator training.”

CMR may represent an ideal risk-stratification tool

Several factors highlighted by the study suggest that CMR “may represent an ideal risk-stratification tool and should form an integral part of chest pain algorithms”. These include the high accuracy with which high-resolution quantitative perfusion CMR can diagnose CMD, the improvement of accuracy with the acquisition of vasodilator stress and rest perfusion imaging compared with stress perfusion alone, and the recognition that angina and NOCAD represents a heterogeneous cohort at risk of cardiovascular morbidity.

Researchers believe that the next step towards the approach could be prospective outcome studies to demonstrate better patient outcomes.

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