Diagnosing Coronary Microvascular Dysfunction in Patients with Non-Obstructive Coronary Artery Disease by Stress Cardiac Magnetic Resonance

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Diagnosing Coronary Microvascular Dysfunction in Patients with Non-Obstructive Coronary Artery Disease by Stress Cardiac Magnetic Resonance

Coronary microvascular dysfunction (CMD) has emerged as a critical pathophysiological factor in patients with angina or signs of myocardial ischemia who present with non-obstructive coronary arteries (NOCA), defined as 0.80 on invasive coronary angiography. CMD is associated with adverse clinical outcomes, yet its diagnosis remains challenging due to the limitations of the current gold standard, coronary reactivity testing (CRT), which is invasive, costly, and not widely accessible. Stress cardiac magnetic resonance (CMR) has gained attention as a non-invasive alternative for diagnosing CMD by quantifying myocardial perfusion parameters such as the myocardial perfusion reserve index (MPRI) and myocardial perfusion reserve (MPR). This article synthesizes evidence from a systematic review and meta-analysis evaluating the diagnostic utility of stress CMR in identifying CMD among NOCA patients.

Methodology and Study Design

A comprehensive literature search was conducted across PubMed, Embase, and Web of Science from January 1, 2000, to January 1, 2024, using predefined search terms related to CMD, NOCA, and stress CMR. Studies were included if they involved patients with suspected coronary artery disease (CAD), confirmed NOCA by angiography, used CRT to define CMD, and reported MPRI or MPR values derived from stress CMR. Exclusion criteria included retracted articles, overlapping cohorts, and non-extractable data. Seven studies met eligibility criteria, with four focusing on MPRI (346 patients) and three on MPR (188 patients).

The methodological quality of included studies was assessed using the National Institutes of Health’s “Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies.” Six studies received a “Good” rating, while one was rated “Fair.” A critical limitation across all studies was the lack of sample size justification.

Key Findings

Myocardial Perfusion Reserve Index (MPRI)

MPRI, calculated as the ratio of myocardial blood flow during stress to rest, was evaluated in four studies. The CMD cohort (263 patients) exhibited significantly lower MPRI values (range: 1.14 ± 0.21 to 1.71 ± 0.43) compared to the non-CMD cohort (83 patients; range: 1.21 ± 0.23 to 2.23 ± 0.37). Pooled analysis revealed a mean difference of −0.64 (95% confidence interval [CI]: −1.15 to −0.13, P = 0.01) between groups, with substantial heterogeneity (I² = 73.09%). The CMD cohort was predominantly female (87.5%) with a mean age of 56.0 years.

Myocardial Perfusion Reserve (MPR)

MPR, another perfusion parameter reflecting the ratio of stress to rest myocardial blood flow, was analyzed in three studies. The CMD group (85 patients) demonstrated lower MPR values (range: 2.00 ± 0.43 to 2.37 ± 0.73) than the non-CMD group (103 patients; range: 2.40 ± 0.52 to 2.68 ± 0.47). The pooled mean difference was −0.91 (95% CI: −1.57 to −0.25, P = 0.01), with significant heterogeneity (I² = 73.11%). Participants in these studies had a mean age of 60.5 years, with 80% being female.

Clinical and Pathophysiological Implications

CMD disrupts the equilibrium between coronary blood flow supply and myocardial demand, leading to ischemia in NOCA patients. CRT-defined CMD includes impaired endothelium-independent vasodilation (coronary flow reserve [CFR] <2.0–2.5 or index of microvascular resistance [IMR] ≥25) and endothelium-dependent dysfunction (abnormal vasoreactivity). Stress CMR indirectly assesses microvascular function by measuring perfusion responses to pharmacological stressors like adenosine, which induces maximal vasodilation. Reduced MPRI and MPR reflect diminished microvascular reserve, consistent with CRT findings.

Recent guidelines endorse stress CMR as a Class IIa recommendation for diagnosing CMD in stable chest pain patients with NOCA. A prior study proposed an MPRI cutoff of ≤1.84 for diagnosing CMD (sensitivity: 73%, specificity: 74%, area under the curve: 78%). However, optimal MPR thresholds remain undefined. Comparative analyses are needed to determine whether MPRI or MPR offers superior diagnostic accuracy.

Heterogeneity and Technical Considerations

The high heterogeneity (I² >73% for both parameters) may stem from variations in CMD phenotypes, stress protocols, and CMR methodologies. For instance, studies using cold pressor testing reported lower MPRI values than those using adenosine, highlighting the influence of stressor type on results. Additionally, magnetic field strength (1.5T vs. 3T) may affect absolute myocardial blood flow measurements, though ratio-based parameters like MPRI and MPR are less susceptible to these differences.

Limitations and Future Directions

The small sample sizes of included studies limit generalizability. Furthermore, pooled analyses did not differentiate between CMD phenotypes (e.g., endothelium-dependent vs. -independent dysfunction), which may have distinct pathophysiological mechanisms. Future research should:

  1. Validate stress CMR against CRT in larger, prospective cohorts.
  2. Establish standardized diagnostic cutoffs for MPRI and MPR.
  3. Investigate the role of alternative stressors (e.g., acetylcholine, exercise) in assessing microvascular function.
  4. Explore the prognostic value of stress CMR parameters in predicting adverse outcomes.

Conclusion

Stress CMR demonstrates significant potential as a non-invasive tool for diagnosing CMD in NOCA patients, with MPRI and MPR serving as robust indicators of microvascular dysfunction. Despite heterogeneity in current evidence, these parameters align with invasive CRT findings and offer actionable insights for clinical management. Standardization of protocols and further validation studies are essential to consolidate stress CMR’s role in routine practice.

doi.org/10.1097/CM9.0000000000003472

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