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Prevalence, Predictors, and Outcomes of Impaired Myocardial Flow Reserve Among Symptomatic Patients with a Coronary
Maria Alwan1, Ahmed Sayed1, Ahmad El Yaman1
1Houston Methodist DeBakey Heart and Vascular Center, Houston, Texas.
Insights
A coronary artery calcium (CAC) score of 0 does not always mean low cardiovascular risk. Impaired myocardial flow reserve (MFR) in these patients predicts adverse events, improving risk assessment.
Area of Science:
- Cardiology
- Nuclear Cardiology
- Preventive Cardiology
Background:
- Coronary artery calcium (CAC) scoring is a guideline-recommended tool for cardiovascular risk assessment.
- A CAC score of 0 traditionally signifies low cardiovascular risk, but may miss noncalcified plaque and microvascular dysfunction.
- Myocardial flow reserve (MFR) assessed by positron emission tomography (PET) may identify subclinical atherosclerosis missed by CAC.
Purpose of the Study:
- To determine the prevalence, predictors, and prognostic significance of impaired PET-derived MFR in patients with a CAC score of 0.
- To evaluate MFR's ability to enhance cardiovascular risk stratification beyond CAC scoring.
Main Methods:
- Analysis of 2,270 symptomatic patients with CAC score of 0 who underwent clinically indicated PET.
- Multivariate logistic regression to identify predictors of impaired MFR.
- Nested Cox models, C-index, and net reclassification improvement (NRI) to assess MFR's prognostic value for major adverse cardiovascular events.
Main Results:
- Impaired MFR was present in 30.5% of patients with CAC score of 0.
- Predictors of impaired MFR included age, morbid obesity, diabetes, hypertension, and chronic kidney disease.
- Impaired MFR was independently associated with a 4.69-fold increased risk of adverse outcomes and significantly improved risk prediction models.
Conclusions:
- Nearly one-third of symptomatic patients with a CAC score of 0 exhibit impaired MFR.
- Impaired MFR is a strong independent predictor of adverse cardiovascular outcomes in this population.
- MFR assessment provides incremental prognostic information, identifying high-risk individuals with CAC score of 0 who may benefit from intensified preventive strategies.
Abstract:
Coronary artery calcium (CAC) scoring has been incorporated into preventive guidelines and is increasingly studied as a gatekeeper to further testing. A CAC score of 0 is traditionally associated with low cardiovascular risk. However, the CAC score primarily quantifies calcified plaque, potentially overlooking noncalcified atherosclerosis and microvascular dysfunction, which also contribute to adverse outcomes. This study aimed to assess the prevalence, predictors, and prognostic value of impaired PET-derived myocardial flow reserve (MFR) in patients with a CAC score of 0. Methods: We analyzed 2,270 symptomatic patients across 2 centers who had a CAC score of 0 and underwent a clinically indicated PET. Multivariate logistic regression was used to identify predictors of impaired MFR. Nested Cox models were used to assess the incremental prognostic value of MFR for a composite of all-cause death, myocardial infarction/late revascularization, and heart failure admission. The C-index and net reclassification improvement (NRI) were also calculated. Results: The prevalence of impaired MFR was 30.5%. Significant predictors included age, morbid obesity (BMI ≥ 40 kg/m2), diabetes, hypertension, and chronic kidney disease. Over a median follow-up of 1.63 y, impaired MFR was associated with higher event rates (hazard ratio, 4.69; 95% CI, 2.69-8.2). Adding MFR improved risk prediction (C-index, 0.784-0.815; P < 0.001; categoric NRI, 0.163; continuous NRI, 0.899). The impact of MFR was most pronounced in the intermediate risk category, upgrading 16.8% of patients (4% annual event rate) and downgrading 53.9% (0.9% annual event rate). Conclusion: One in 3 symptomatic patients with a CAC score of 0 had impaired MFR, which was independently associated with adverse outcomes. MFR enhanced risk stratification, highlighting its utility in identifying high-risk individuals with a CAC score of 0 who may benefit from intensive therapy.
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