The main findings of this study in patients with type 2 diabetes are:
Whereas several OCT-derived plaque parameters are predictors for ACS, only mean lipid arc, lipid plaque length, presence of macrophages and minimal FCT were independent predictors.
When combined to a score, these four independent risk factors identify culprit lesions of patients with ACS with excellent diagnostic efficiency.
Features of the ruptured plaque
Several investigations have described certain lesion morphologies to be found more frequently in patients with ACS compared to those with SAP -,. Thus, histopathological studies have identified a lower FCT (<65 μm) overlying a large lipid core, a higher incidence of thin-capped fibroatheromas (TCFA) and an increased macrophage infiltration within the plaque ,, as pivotal precursors for plaque rupture and concomitant cardiovascular events in ACS patients .
With the emerging use of virtual histology IVUS it was possible to prospectively confirm that ACS usually arise from the rupture of insignificant lesions with a thin FCT . The Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT)-study demonstrated that coronary non-culprit lesions causing future major adverse cardiovascular events had a baseline diameter stenosis of only 32%, but were associated with more TCFAs, a greater plaque burden and a minimal lumen area <4 mm2 using virtual histology IVUS . On the contrary, when focusing on coronary culprit lesions, the above and several other studies indicated that lesion severity in culprit lesions is generally greater than 50% in the majority of ACS cases ,-. In this context, Tian et al. compared morphologic plaque characteristics between culprit and non-culprit lesions and reported that plaque rupture is determined by FCT and a combination of large plaque burden and luminal narrowing is a prerequisite for the development of acute coronary syndromes . These findings are in line with the ATHEROREMO-IVUS study, which recently identified TCFAs and a large plaque burden (>70%) as independent predictors for the occurrence of cardiovascular events in coronary non-culprit lesions . The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) study revealed that anatomic burden of coronary artery disease predicts the risk of death, myocardial infarction and non-ST-elevation ACS .
Furthermore, subjects with extensive coronary artery calcification as derived by computed-tomography were associated with a rather stable clinical course and presented a high level of chronic cardiovascular events compared to patients with mild and moderate coronary artery calcification, which more frequently presented with an ACS . This finding strengthens our observations in the present study as it indicates a potentially plaque-stabilizing effect of coronary calcification, whereas soft, predominantly lipid-rich lesions with a thin fibrous cap may rather tend to rupture due to their lower resistance towards intracoronary forces .
Currently there is a paucity of data regarding vulnerable plaque criteria in patients with type 2 diabetes. However, diabetic patients are at a particular high risk for cardiovascular events and the identification of vulnerable plaques and vulnerable plaque features is crucial in this population. Our own group has previously demonstrated that diabetic patients with ACS exhibit more vulnerable plaque characteristics in coronary target lesions compared to diabetics with SAP . Moreover, we were able to point out an association between a lower minimal fibrous cap thickness of coronary culprit lesions to both hemodynamic relevance of a coronary lesion as well as to left ventricular dilatation in exclusively diabetic cohorts ,.
The present study is consistent with the above investigations and adds to the current knowledge by the identification of vulnerable plaque features in patients with type 2 diabetes. Specifically, we demonstrate more frequent lipid-rich plaques, a larger necrotic core and a lower fibrous cap thickness in diabetic patients with ACS compared to those with SAP.
Quantifying plaque vulnerability
However, the individual and combined power of these plaque features to quantify plaque vulnerability is incompletely understood. To the best of our knowledge this study is first to summarize these previously and individually established parameters of plaque vulnerability to a score. Whereas we and others have found non-plaque derived parameters such as left ventricular dilatation to be predictors for plaque vulnerability ,,, we confined the present investigation to OCT-derived plaque parameters to quantify plaque vulnerability. Using the novel imaging modality OCT with its superior resolution compared to IVUS, the present analysis was able to include additional parameters of plaque vulnerability, such as macrophage infiltration and the presence of microchannels ,. Thus, we expand the current knowledge by demonstrating that among all morphologic plaque parameters studied by OCT, only minimal FCT, presence of macrophages, mean lipid arc and lipid plaque length are independent predictors of the lesion to be the cause for an ACS in patients with type 2 diabetes. Whereas previous studies have also described these parameters as vulnerable plaque features ,, we found that minimal FCT had the best diagnostic efficiency to quantify plaque vulnerability among all OCT-derived parameters investigated.
Furthermore, when combined to a score, these risk factors offer an excellent diagnostic efficiency to quantify plaque vulnerability and to identify culprit lesions of diabetic patients with ACS.
Using plaque vulnerability to guide coronary interventions
The Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME)-study had previously demonstrated a reduction in cardiovascular events if coronary interventions were guided by fractional flow reserve (FFR) rather than angiography alone ,. However, neither ischemic nor anatomic burden were able to distinctly identify patients who would benefit from an invasive revascularization strategy over optimal medical therapy in COURAGE . Thus, these data emphasize the importance of optimal medical therapy on the one hand and also – more importantly – the need for alternative diagnostic and therapeutic strategies to guide and optimize coronary interventions on the other hand. In this regard, a score to quantify the vulnerability of a coronary lesion might be of interest.
Using the OCT-risk score for plaque vulnerability presented in this study it may be possible to unmask those lesions at risk to cause an ACS in high-risk patients with type 2 diabetes. Therefore, our findings possibly indicate that OCT may be essential for guiding the clinical decision for revascularization beyond angiographic or hemodynamic lesion severity. As this novel score focuses on the overall and combined impact of single features of plaque vulnerability it may have the potential to be a valuable and convenient tool for clinical risk-stratification and clinical decision-making. Moreover, this score may support and extend the clinical indication spectrum for OCT and in selected cases may be an alternative and/or complement to FFR, which has hitherto been the gold-standard for evaluating the PCI indication ,,. This applies in particular to lesions in which the relevance of the FFR technique is either limited, such as in case of serial stenoses or challenging anatomic sites, like left main or bifurcation lesions, or if FFR measurements lack clear hemodynamic significance despite advanced angiographic stenosis severity or persistent clinical symptoms.
Thus, this score may help to guide PCI in lesions in which FFR measurements are either not reliable or applicable. However, if FFR assessment displays hemodynamic relevance of a coronary stenosis, PCI should be performed irrespective of the value of our score.
Future studies are warranted to evaluate this score in prospective trials and to determine if coronary interventions guided by this score reduce cardiovascular morbidity and mortality in patients with type 2 diabetes. The present investigation may be the basis for further clinical studies to validate this score in larger diabetic as well as non-diabetic cohorts.
Although the current study is hitherto the largest OCT-study in an exclusively diabetic cohort, the relatively small sample size limits the precision of the regression coefficients.
Second, large randomized studies are required to evaluate whether our score may actually help to reduce cardiovascular morbidity and mortality in high-risk patients with type 2 diabetes.
Third, as we have excluded patients with hemodynamic instability or cardiogenic shock our data may only partially reflect the true incidence of plaque ruptures and specific plaque features in ACS patients.
Finally, as this is a study in an exclusively diabetic cohort, future studies are needed to determine if this score can also be applied to patients without diabetes.