Ismail Dogu Kilic

Inducing Persistent Flow Disturbances Accelerates Atherogenesis and Promotes Thin Cap Fibroatheroma Development in D374Y-PCSK9 Hypercholesterolemic Minipigs.

Background— Although disturbed flow is thought to play a central role in the development of advanced coronary atherosclerotic plaques, no causal relationship has been established. We evaluated whether inducing disturbed flow would cause the development of advanced coronary plaques, including thin cap fibroatheroma. Methods and Results— D374Y-PCSK9 hypercholesterolemic minipigs (n=5) were instrumented with an intracoronary shear-modifying stent (SMS). Frequency-domain optical coherence tomography was obtained at baseline, immediately poststent, 19 weeks, and 34 weeks, and used to compute shear stress metrics of disturbed flow. At 34 weeks, plaque type was assessed within serially collected histological sections and coregistered to the distribution of each shear metric. The SMS caused a flow-limiting stenosis, and blood flow exiting the SMS caused regions of increased shear stress on the outer curvature and large regions of low and multidirectional shear stress on the inner curvature of the vessel. As a result, plaque burden was ≈3-fold higher downstream of the SMS than both upstream of the SMS and in the control artery (P<0.001). Advanced plaques were also primarily observed downstream of the SMS, in locations initially exposed to both low (P<0.002) and multidirectional (P<0.002) shear stress. Thin cap fibroatheroma regions demonstrated significantly lower shear stress that persisted over the duration of the study in comparison with other plaque types (P<0.005). Conclusions— These data support a causal role for lowered and multidirectional shear stress in the initiation of advanced coronary atherosclerotic plaques. Persistently lowered shear stress appears to be the principal flow disturbance needed for the formation of thin cap fibroatheroma.

microRNA -143 and -223 in obesity

BACKGROUND Obesity alters endocrine and metabolic functions of adipose tissue and has been recognized as a chronic inflammatory disease, which in turn may contribute to the development of insulin resistance, type 2 diabetes, obesity-associated vasculopathy and cardiovascular disease. The pathogenesis of obesity involves many regulatory pathways including transcriptional regulatory networks, including microRNAs. METHODS A total of 83 patients were included in the study. Patients were recruited from a cardiology outpatient clinic and were allocated into 3 age- and sex-matched groups according to their body mass index. Group 1 included 23 morbidly obese, group 2 30 obese, and group 3 30 normal or overweight subjects. RESULTS In our study, we showed that miR-143 and miR-223 levels were significantly lower in groups 1 and 2 than the control group (normal BMI or overweight). CONCLUSIONS Obesity leads to alterations in miRNA expressions and miRNA-143 and -223s can be used as biomarkers for the metabolic changes in obesity.

Is high pressure postdilation safe in bioresorbable vascular scaffolds? Optical coherence tomography observations after noncompliant balloons inflated at more than 24 atmospheres.

Optical coherence tomography (OCT) was used to investigate integrity and expansion of bioresorbable drug‐eluting scaffolds (BVS) after high‐pressure postdilation (HPPD).

Near-infrared spectroscopy-intravascular ultrasound: scientific basis and clinical applications

Coronary angiography underestimates the magnitude of the atherosclerotic burden and cannot detect the presence of disease in the early phases. Recognition of these inherent limitations of angiography has been an impetus for the development of other coronary imaging techniques. The novel near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) catheters can detect and quantify the presence of lipid core in the atherosclerotic plaque and associate it with other features such as lumen size and plaque architecture. Lipid-rich plaques are known to pose a higher risk of distal embolization during interventions and plaque disruption. The aim of this manuscript is the review of the potential clinical and research applications of this technology as highlighted by recent studies.

Aortic pressures, stiffness and left ventricular function in coronary slow flow phenomenon.

Background: Coronary slow flow (CSF) phenomenon is characterized by delayed opacification of coronary vessels in a normal coronary angiogram. Although clinical and pathological features have been previously described, the underlying pathophysiology has not been fully elucidated. In this study, we aimed to evaluate central aortic pressure, aortic stiffness and left ventricular (LV) function in patients with coronary slow flow. Method and Results: The study population consisted of 154 patients who underwent coronary angiography because of typical and quasi-typical symptoms of angina. 81 patients with angiographically proven CSF and 73 cases with normal coronary flow pattern with similar risk profiles were enrolled in the study. Aortic pressures and indexes of elastic properties were evaluated using invasive methods. Aortic pulse pressure (mm Hg) and pulsality index of patients with CSF were found to be significantly higher than those of controls (60.8 ± 13.8 vs. 53.7 ± 14.5, p = 0.002; 0.84 ± 0.22 vs. 0.67 ± 0.18, p = 0.0001, respectively). LV Doppler parameters were deteriorated in patients with CSF. Aortic fractional pulse pressure and pulsality index were significantly correlated with the mean TIMI frame count and LV diastolic parameters in correlation analysis. Conclusion: The present findings allow us to conclude that impaired aortic elasticity in patients with CSF may also be responsible for the impaired LV diastolic parameters.

Coronary Artery Aneurysms: A Review of the Epidemiology, Pathophysiology, Diagnosis, and Treatment

Coronary artery aneurysms (CAAs) are uncommon and describe a localized dilatation of a coronary artery segment more than 1.5-fold compared with adjacent normal segments. The incidence of CAAs varies from 0.3 to 5.3%. Ever since the dawn of the interventional era, CAAs have been increasingly diagnosed on coronary angiography. Causative factors include atherosclerosis, Takayasu arteritis, congenital disorders, Kawasaki disease (KD), and percutaneous coronary intervention. The natural history of CAAs remains unclear; however, several recent studies have postulated the underlying molecular mechanisms of CAAs, and genome-wide association studies have revealed several genetic predispositions to CAA. Controversies persist regarding the management of CAAs, and emerging findings support the importance of an early diagnosis in patients predisposed to CAAs, such as in children with KD. This review aims to summarize the present knowledge of CAAs and collate the recent advances regarding the epidemiology, etiology, pathophysiology, diagnosis, and treatment of this disease.

Optical coherence tomography guidance for percutaneous coronary intervention with bioresorbable scaffolds.

BACKGROUND The effect of optical coherence tomography (OCT) guidance on the implantation strategy during all phases of percutaneous coronary intervention (PCI) with bioresorbable vascular scaffolds (BVSs) in a real-world scenario has been poorly investigated. METHODS Consecutive patients undergoing BVS implantation at our institution were included in this registry. Frequency-domain OCT pullbacks were performed at the operators discretion during all phases of BVS implantation procedures to optimize preparation of lesions, confirm BVS size, and optimize expansion and apposition of scaffolds. RESULTS Between September 2012 and July 2015, 203 BVSs were implanted in 101 consecutive patients at our institution (2.01 BVSs/patient). In 66 patients, the procedure was performed under OCT guidance. In the OCT subgroup, 66 (77.6%) of the 85 treated lesions were complex (B2/C AHA/ACC type). Overall, 147 OCT pullbacks were performed and 72/147 (49.0%) pullbacks indicated the need for changing strategy. After angiography-only-guided optimisation of BVS in 27 (31.8%) lesions, an OCT examination prompted performance of a second post-expansion. This resulted in an increase in the minimal scaffold area (5.5 to 6.3mm(2), p=0.004) and a decrease in the incomplete scaffold apposition area (1.1 to 0.6mm(2), p=0.082), with no new stent fractures. When the population was divided according to the time of BVS implantation, an initial learning adaptation became evident, with the number of OCT-guided changes in strategy significantly decreasing between the initial and final time periods (p=0.017). CONCLUSIONS OCT guidance for BVS implantation significantly affects the procedural strategy, with favourable effects on acute results and the learning curve.

Noninvasive indicators of atherosclerosis in subclinical hypothyroidism.

Introduction: Cardiovascular system is rich in thyroid hormone receptors and is one of the major sites of action for thyroid hormones. However, the effect of subclinical hypothyroidism (SCH) on atherosclerosis has not been cleared yet. Materials and Methods: SCH is defined as high thyroid-stimulating hormone (TSH) levels in the presence of normal serum T4 and T3 levels. A total of 32 patients with SCH and 29 controls were included in the study. Carotid intima-media thickness, flow-mediated dilatation, and aortic distensibility were compared between the groups. Results: FMD was lower in patients with SCH than in controls. GTN-induced vasodilatation was similar in the patients with SCH and controls. There was no statistically significant difference between the patients with SCH and controls with respect to CIMT and aortic distensibility. Conclusion: SCH is associated with endothelial dysfunction as established by FMD. Inconsistent results of CIMT and aortic stiffness can be explained by these parameters being measures of structural changes whereas FMD is a dynamic measure that reflects the impact of both acute and chronic influences on endothelial function.

Thrombus Aspiration in Primary Angioplasty for ST-segment Elevation Myocardial Infarction

Mechanical reperfusion with primary percutaneous coronary intervention in acute ST-segment-elevation myocardial infarction is superior to fibrinolysis in terms of short-term and long-term outcome, provided that it can be delivered on time and by an experienced team. Balloon angioplasty and stent implantation of an occluded epicardial vessel during ST-segment-elevation myocardial infarction can cause disruption of the frail thrombus containing lesions associated with suboptimal myocardial reperfusion and microcirculatory obstruction. Distal embolization of atherothrombotic material can be prevented by thrombus aspiration during primary angioplasty. Mechanical aspiration via end-hole large-lumen thrombectomy catheters has been shown to improve Thrombolysis in Myocardial Infarction (TIMI) flow and result in a more consistent early resolution of ST-segment elevation in multiple registries. More recently, a more sophisticated quantification of the myocardial damage has been applied using myocardial scintigraphy and magnetic resonance, with no difference between patients treated with thrombectomy and patients treated with conventional therapy. The expectations in terms of lasting mortality benefit raised by the first Dutch single-center randomized trial of thrombectomy versus predilation with plain old balloon angioplasty (Thrombus Aspiration During Percutaneous Coronary Intervention in Acute Myocardial Infarction, TAPAS) were not confirmed by a much larger Swedish trial (Thrombus Aspiration ST-Segment Elevation Myocardial Infarction, TASTE) showing no outcome changes. Although we are waiting for new trials to clarify these controversial results, thrombectomy is still used in selected patients with high thrombus load or with persistent occlusion of the infarct-related artery after wire passage. Here we review the various systems available and discuss their relative merits and the reported results.

Indications and immediate and long‐term results of a novel pericardium covered stent graft: Consecutive 5 year single center experience

The use of covered stent grafts during percutaneous coronary intervention (PCI) is a life saving solution to seal acute iatrogenic vessel rupture. However, the presence of an impenetrable mechanical barrier is also appealing during treatment of friable coronary plaques but the synthetic PTFE‐membrane that might trigger excessive neointimal proliferation has limited its elective‐use. Pericardium tissue may offer an appealing “natural” alternative. Aim of our study is to report the consecutive 5‐year single center experience with the use of pericardium‐covered stents (PCS) (ITGI‐Medical, Israel) in a variety of emergency and elective applications.