Relationship betweeen the amount and location of macrophages and clinical outcome: subanalysis of the CLIMA-study.

BACKGROUND: The ability of optical coherence tomography (OCT) to recognize intraplaque macrophage infiltration is now well acknowledged. This post-hoc analysis of the CLIMA study aimed to address the clinical impact of the circumferential extension of OCT-defined macrophages and their location at one year follow-up. METHODS: The multicentre CLIMA study enrolled 1003 patients undergoing OCT evaluation of the untreated proximal left anterior descending (LAD) coronary artery. Measurements of circumferential extension of macrophages and measurements of the distance from intima-lumen contour to macrophages string were performed at the plaque cross-section judged as containing the greatest amount of macrophages. The main study endpoint was a composite of cardiac death, myocardial infarction (MI) and/or target vessel revascularization (TVR). RESULTS: Patients with large macrophage arc (p = 0.001) and superficial macrophage arc (p < 0.001) showed a higher one-year incidence of the main one-year composite endpoint. Consistently hypertension (p = 0.018), family history of CAD (p = 0.046), diabetes mellitus (p = 0.036), lower ejection fraction (p = 0.009) and chronic kidney disease (p = 0.019) were more frequently found in patients experiencing the main composite endpoint. At multivariate Cox regression analysis, fibrous cap thickness < 75 µm (HR 2.51, 95% 1.46-4.32), presence of large (HR 1.97, 95%CI 1.16-3.35, p = 0.012) and superficial (HR 1.72, 95%CI 1.02-2.90; p = 0.040) macrophage arc remained independent predictors of the main composite endpoint. Large macrophage arc was associated with target LAD related MI. CONCLUSION: The present post-hoc analysis of the CLIMA showed that the circumferential extension of macrophages and their location are related to a composite endpoint of cardiac death, MI and/or TVR.

The "RotaTripsy Plus" Approach in a Heavily Calcified Coronary Stenosis.

Percutaneous treatment of heavily calcified coronary stenoses is one the most demanding setting, due to the high risk of acute and long-term complications. Various dedicated devices are currently available and their combined use can be an option in these high-risk procedures. We hereby report a successful case of several combined debulking technologies for the treatment of a long, highly calcified coronary lesion.

Prevalence and quantitative assessment of macrophages in coronary plaques.

Although optical coherence tomography (OCT) proved to be able to identify macrophage clusters, there are no available data on the possibility to obtain reproducible measurements of their circumferential extension and location. The purpose of the present post-hoc analysis of the CLIMA study was to revise the clinical and demographic variables of patients having coronary plaques with macrophages and to investigate the reproducibility of their quantitative assessment. A total of 577 patients out of 1003 undergoing OCT showed macrophage accumulation. Three groups were identified; group 1 (426 patients) without macrophages, group 2 (296) patients with low macrophage content (less than median value [67°] of circumferential arc) and group 3 (281) with high macrophage content arc [> 67°]. Patients with macrophages (groups 2 and 3) showed a higher prevalence of family history for coronary artery disease and hypercholesterolemia and had a significantly larger body mass index. Furthermore, group 3 had more commonly triple vessel disease and higher value of LDL cholesterol levels compared to the two other groups. The inter-observer agreement for macrophage interpretation was good: R values were 0.97 for the circumferential arc extension, 0.95 for the minimum distance and 0.98 for the mean distance. A non-significant correlation between circumferential extension of macrophages and hsCRP values was found (R = 0.013). Quantitative assessment of macrophage accumulations can be obtained with high reproducibility by OCT. The presence and amount of macrophages are poorly correlated with hsCRP and identify patients with more advanced atherosclerosis and higher LDL cholesterol levels.

Clinical outcomes of calcified nodules detected by optical coherence tomography: a sub-analysis of the CLIMA study.

AIMS: The goal of the present post hoc analysis of the CLIMA registry was to establish the relationship between calcified nodules (CNs) with (CND) or without (CNWD) disruption of the superficial intimal fibrous layer and one-year occurrence of target lesion myocardial infarction (MI) and/or cardiac death. METHODS AND RESULTS: CND and CNWD were identified based on the presence or absence of superficial irregularities indicative of disruption of the intimal fibrous layer, with possible overlying local thrombus. In total, 222 CNs were found in the 1,776 non-culprit LAD plaques. CND had larger maximum calcific arc and smaller lumen area. Cardiac death and MI occurred in 20% of patients in the CND group versus 2.7% in the CNWD group and 3.3% in the group without CN (p<0.001). This figure was mainly due to the 13.3% incidence of cardiac death in the CND group versus 2.0% in the CNWD group and versus 2.2% in the group without CN (p<0.001). The presence of CND was confirmed as an independent predictor of events (HR 6.58, 95% CI: 2.7-15.8, p<0.001). CONCLUSIONS: The presence of CND was associated with a high one-year incidence of cardiac death and/or target lesion MI.

'Precision medicine' and ischaemic heart disease: the stage is set for the new antibody based therapies (lipid lowering and anti-inflammatory).

Improving cardiovascular risk assessment requires a 'personalized' approach. Appraisal of well-known cardiovascular risk factors should be integrated with markers of cardiovascular risk such as LDL cholesterol (C-LDL) and C-reactive protein (CRP). Results of the recent trials of PCSK9 inhibitor monoclonal antibodies open new interesting perspective. Data regarding the use of Evolocumab, in secondary prevention settings, in high-risk patients are very encouraging. In the same vein, the CANTOS study demonstrated, for the first time, that Canakinumbab, an antibody with anti-inflammatory action (with no effects on C-LDL levels), decreases significantly the risk of major cardiovascular events in a high-risk population with elevated CRP and optimal C-LDL. This trial, for the first time, suggested a strategy distinguishing the anti-inflammatory from the cholesterol lowering component, thus differentiating the treatment. In the ensuing years, we will probably witness the clinical application of this concept.

Role of optical coherence tomography in identifying sub-optimal stent positioning and predicting major adverse cardiac events in a comparative study with angiography: a CLIO-OPCI II sub-study.

BACKGROUND: Quantitative coronary angiography (QCA) is the gold standard for evaluating correct stenting, despite its limitation in recognizing features indicative of suboptimal deployment. This subanalysis of the CLI-OPCI II registry addressed the role of optical coherence tomography (OCT) to verify whether suboptimal OCT deployment occurs in the presence of an optimal angiographic result. PATIENTS AND METHODS: We retrospectively analyzed 125 lesions in the 105 patients with major adverse cardiac events of the CLI-OPCI II. Every lesion was evaluated with OCT and angiography, including visual and QCA assessment. Optimal angiographic result was defined as residual stenosis of less than 30% at QCA and absence of haziness at visual angiography. The following OCT features of suboptimal stenting were considered: edge dissection (linear rim of tissue with a width >200 µm), reference lumen narrowing (lumen area <4.5 mm in the presence of significant residual plaque adjacent to stent endings), and in-stent narrowing (minimum lumen area<4.5 mm). RESULTS: Among the 125 lesions, 105 showed an optimal angiographic result. At OCT, a suboptimal positioning was common (56%). In the group of optimal angiographic results, OCT showed a suboptimal deployment in 54% of cases. Minimum lumen area of less than 4.5 mm, distal and proximal reference narrowing, and distal edge dissections were found in 30, 25, 15, and 7% of cases, respectively. CONCLUSION: This substudy of the CLI-OPCI II showed that in patients with major adverse cardiac events, the presence of an optimal postintervention angiographic appearance with suboptimal OCT metrics is a frequent finding. Our data further support the effectiveness of OCT, which provide valuable information even in the presence of optimal poststenting angiographic results.