Editor's Note: The papers by Ferreira's group and the accompanying editorial were retracted in September 2020 due to data fabrication that undermined the findings and conclusions. A full explanation by the journal can be found and .
Two novel cardiac MRI techniques performed well under testing, paving the way to the detection of microvascular coronary artery disease (CAD), researchers in England reported.
Stress T1 Mapping
Action Points
- Be aware that cardiac MRI stress T1 mapping accurately detected and differentiated between obstructive epicardial coronary artery disease (CAD) and microvascular dysfunction, without contrast agents or radiation, and was superior to gadolinium-based first-pass perfusion imaging for detecting obstructive epicardial CAD.
- Be aware, also, that in angina patients with non-obstructive coronary artery disease, cardiac magnetic resonance imaging can objectively and noninvasively assess microvascular angina.
In a head-to-head comparison with gadolinium-based first-pass perfusion imaging, stress T1 mapping was better for detecting obstructive epicardial CAD (AUC 0.97 versus 0.91, P<0.001), reported Vanessa Ferreira, MD, DPhil, of the University of Oxford John Radcliffe Hospital in the U.K., and colleagues in the March 6 issue of the. Fractional flow reserve and the index of microcirculatory resistance served as reference.
Stress T1 mapping detects ischemia and myocardial blood volume changes without contrast agents. Normal myocardial T1 reactivity was 6.2% on both 1.5- and 3-T cardiac MRI scans, whereas it was blunted in the case of ischemic viable myocardium downstream of obstructive CAD (0.7%) and myocardium downstream of nonobstructive coronary arteries with microvascular dysfunction (3.0%).
Ferreira's group found that a T1 threshold of 1.5% detected obstructive CAD with 93% sensitivity and 95% specificity, whereas T1 at 4.0% drew the line for accurately detecting microvascular dysfunction (AUC 0.95; sensitivity 94%; specificity 94%).
"[Cardiac MRI] stress T1 mapping accurately detected and differentiated between obstructive epicardial CAD and microvascular dysfunction, without contrast agents or radiation," the team concluded.
In an , Theodoros Karamitsos, MD, PhD, of Aristotle University of Thessaloniki, AHEPA Hospital, in Greece, wrote: "A key finding of this study is that stress T1 mapping performed better, on a vessel-based analysis, than standard first-pass stress perfusion [cardiac MRI] irrespective of the analysis method (visual, semi-quantitative, or quantitative). Another important finding is that stress/rest T1 mapping can differentiate between epicardial obstructive CAD and coronary microvascular dysfunction with excellent interscan and intrascan reproducibility."
The study included 60 patients with angina and 30 normal controls. All subjects underwent cardiac MRI to assess function, ischemia, and scar imaging.
Having selected patients without complex CAD was a caveat of the analysis, the authors acknowledged.
Karamitsos explained that another limitation is that manual or semi-automated contouring is necessary to determine T1 values and measure myocardial perfusion reserve index (MPRI) or myocardial blood flow, but that method is time-consuming. "Furthermore, T1 mapping was performed with a specific sequence, namely the Shortened Modified Look-Locker inversion recovery sequence, which carries some unique characteristics for dynamic stress imaging.
"The plethora of different T1 mapping methods, which have different properties and diverging normal reference values, generates confusion and uncertainty whether results of one study can be confirmed on a similar patient population with a different T1 mapping method," he said.
MPRI
A separate , also by Ferreira et al, showed that myocardial perfusion assessed by cardiac MRI could flag myocardial ischemia from coronary microvascular dysfunction.
The MPRI threshold that detected inducible myocardial ischemia from obstructive CAD (AUC 0.95, 95% CI 0.85-0.99) was also useful for patients with three-vessel non-obstructive CAD to detect inducible ischemia due to coronary microvascular dysfunction (AUC 0.90, 95% CI 0.80-0.96; specificity 95%, sensitivity 89%, accuracy 92%), the researchers reported.
Raising the MPRI threshold to 1.6 yielded a negative predictive value of 95% and sensitivity of 94% for ruling out significant inducible ischemia due to coronary microvascular dysfunction.
Additionally, mild coronary microvascular dysfunction may be caught using a stress myocardial blood flow (MBF) threshold of 2.3 ml/min/g with 100% positive predictive value and 100% specificity (AUC 0.76; 95% CI: 0.63 to 0.86).
"Integration of MPRI and MBF assessment into the clinical [cardiac MRI] workflow can provide a noninvasive approach for evaluating both epicardial and microvascular CAD in patients with angina, which deserves further validation in an all-comers population," the investigators concluded.
"In previous studies, microvascular ischemia has largely been a diagnosis of exclusion, rather than being objectively demonstrated, due to either the complete lack of validation against invasive reference standards for CMD or validation against invasive markers that are not specific for the microcirculation, such as coronary flow reserve or coronary reactivity testing," they added.
For this single-center study, a total of 50 patients with angina were matched by age with 20 controls. All participants underwent adenosine stress cardiac MRI without T1 mapping.
"Overall, the authors should be commended for performing two important studies that open new frontiers for myocardial ischemia testing," Karamitsos said in the editorial, which referred to both studies. He added that the prospective application of these proposed MPRI and T1 thresholds to detect obstructive and nonobstructive CAD will be "necessary" in future large-scale clinical studies.
Disclosures
The studies were funded by a British Heart Foundation Clinical Research Training Fellowship grant.
Ferreira and three co-authors reported support from the National Institute for Health Research Biomedical Research Centre and the British Heart Foundation Centre of Research Excellence; other co-authors reported having no relationships relevant to the study to disclose.
For the second study, one co-author reported being an employee of Siemens Healthcare and another holding patent authorship for Shortened Modified Look-Locker inversion recovery T1 mapping with all rights transferred to Siemens Medical.
Karamitsos reported having no relevant conflicts of interest.
Additional Source
Journal of the American College of Cardiology
Liu A, et al "Gadolinium-free cardiac MR stress T1-mapping to distinguish epicardial from microvascular coronary disease" J Am Coll Cardiol 2018; 71 (9): 957-968.