Spotty calcium deposits within acute coronary syndrome (ACS)-causing culprit lesions impact inflammatory vessel-wall interactions and are associated with higher cardiovascular event rates at one year follow-up: Results from the prospective translational OPTICO-ACS study program.

BACKGROUND AND AIMS: Spotty calcium deposits (SCD) represent a vulnerable plaque feature which seems to result - as based on recent invitro studies - from inflammatory vessel-wall interactions. SCD can be reliably assessed by optical coherence tomography (OCT). Their prognostic impact is yet unknown. Therefore, the aims of this translational study were to comprehensively characterize different plaque calcification patterns, to analyze the associated inflammatory mechanisms in the microenvironment of acute coronary syndrome (ACS)-causing culprit lesions (CL) and to investigate the prognostic significance of SCD in a large cohort of ACS-patients. METHODS: CL of the first 155 consecutive ACS-patients from the translational OPTICO-ACS-study program were investigated by OCT-characterization of the calcium phenotype at ACS-causing culprit lesions. Simultaneous immunophenotyping by flow-cytometric analysis and cytokine bead array technique across the CL gradient (ratio local/systemic levels) was performed and incidental major adverse cardiovascular events plus (MACE+) at 12 months after ACS were assessed. RESULTS: SCD were observed within 45.2% of all analyzed ACS-causing culprit lesions (CL). Culprits containing spotty calcium were characterized by an increased culprit ratio of innate effector cytokines interleukin (IL)-8 [2.04 (1.24) vs. 1.37 (1.10) p < 0.05], as well as TNF (tumor necrosis factor)-α [1.17 (0.93) vs. 1.06 (0.89); p < 0.05)] and an increased ratio of circulating neutrophils [0.96 (0.85) vs. 0.91 (0.77); p < 0.05] as compared to culprit plaques without SCD. Total monocyte levels did not differ between the two groups (p = n.s.). However, SCD-containing CLs were characterized by an increased culprit ratio of intermediate monocytes [(1.15 (0.81) vs. 0.96 (0.84); p < 0.05)] with an enhanced surface expression of the integrin receptor CD49d as compared to intermediate monocytes derived from SCD-free CLs [(1.06 (0.94) vs. 0.97 (0.91)] p < 0.05. Finally, 12 months rates of MACE+ were higher in patients with, as compared to patients without SCD at CL (16.4% vs. 5.3%; p < 0.05). CONCLUSIONS: This study for the first time identified a specific inflammatory profile of CL with SCD, with a predominance of neutrophils, intermediate monocytes and their corresponding effector molecules. Hence, this study advances our understanding of ACS-causing CL and provides the basis for future personalized anti-inflammatory, therapeutic approaches to ACS.

Challenges of the newer generation of resorbable magnesium scaffolds: Lessons from failure mechanisms of the past generation.

Bioresorbable scaffolds (BRS) were developed to overcome the obstacles of metallic stents, mostly related to sustained presence of metallic foreign body in the coronary vessel. Following earlier success of single-arm BRS studies, randomized controlled trials of Absorb bioresorbable vascular scaffold (Abbott Vascular, Santa Clara, CA, USA) showed poor long-term clinical outcomes, particularly in terms of scaffold thrombosis. BRS made from magnesium alloy provide a promising alternative in terms of radial force, strut thickness and, potentially lower thrombogenicity. A recent clinical study demonstrated that magnesium-based BRS seems to be promising with regards to the risk of scaffold thrombosis. In this review, our aim is to describe the issues that prevented Absorb BVS from achieving favorable outcomes, provide current status of existing BRS technologies and the challenges that newer generation BRSs need to overcome, and the results of clinical studies for commercially available magnesium-based BRS, which remain the only BRS actively studied in clinical practice.

Intravascular molecular imaging: translating pathophysiology of atherosclerosis into human disease conditions.

Progression of atherosclerotic plaque in coronary arteries is characterized by complex cellular and non-cellular molecular interactions. Within recent years, atherosclerosis has been recognized as inflammation-driven disease condition, where progressive stages are characterized by morphological changes in plaque composition but also relevant molecular processes resulting in increased plaque vulnerability. While existing intravascular imaging modalities are able to resolve key morphological features during plaque progression, they lack capability to characterize the molecular profile of advanced atherosclerotic plaque. Because hybrid imaging modalities may provide incremental information related to plaque biology, they are expected to provide synergistic effects in detecting high risk patients and lesions. The aim of this article is to review existing literature on intravascular molecular imaging approaches, and to provide clinically oriented proposals of their application. In addition, we assembled an overview of future developments in this field geared towards detection of patients at risk for cardiovascular events.