Ilaria Dato

Myeloperoxidase: A New Biomarker of Inflammation in Ischemic Heart Disease and Acute Coronary Syndromes

Myeloperoxidase (MPO) is an enzyme stored in azurophilic granules of polymorphonuclear neutrophils and macrophages and released into extracellular fluid in the setting of inflammatory process. The observation that myeloperoxidase is involved in oxidative stress and inflammation has been a leading factor to study myeloperoxidase as a possible marker of plaque instability and a useful clinical tool in the evaluation of patients with coronary heart disease. The purpose of this review is to provide an overview of the pathophysiological, analytical, and clinical characteristics of MPO and to summarize the state of art about the possible clinical use of MPO as a marker for diagnosis and risk stratification of patients with acute coronary syndrome (ACS).

Comparison of the effects of ramipril versus telmisartan on high-sensitivity C-reactive protein and endothelial progenitor cells after acute coronary syndrome.

To compare the anti-inflammatory and endothelial progenitor cell mobilizing effects of ramipril and telmisartan in patients presenting with acute coronary syndrome (ACS), 42 patients with ACS were randomized after successful percutaneous coronary intervention to ramipril 5 mg/day (22 patients) or telmisartan 80 mg/day (20 patients). Peripheral blood samples were drawn at baseline and at 20 days to measure high-sensitivity C-reactive protein and to assess 4 populations of progenitor cells by flow cytometry, namely CD34+/KDR+, CD34+/CD133+, CD34+/CD133+/CD45-, and CD34+/KDR+/CD45- cells. High-sensitivity C-reactive protein levels, similar in the 2 groups at baseline, were significantly more decreased by telmisartan than by ramipril at follow up (p = 0.013 for time-by-drug interaction). The main effect for time was also significant (p <0.001). CD34+/KDR+ and CD34+/CD133+ cells were similar at baseline and did not change over time (p = 0.2 and p = 0.1, respectively). In contrast, for CD34+/KDR+/CD45- and CD34+/CD133+/CD45- cells, a significant increase with time was seen (p = 0.02 and p = 0.002, respectively) and no differential effect of either drug was seen. In conclusion, telmisartan shows a more potent anti-inflammatory effect than ramipril after an ACS. The 2 drugs do not show a differential effect on endothelial progenitor cell mobilization.

Frequency domain optical coherence tomography to assess non-ostial left main coronary artery

AIMS The aim of this study was to assess the feasibility of unprotected non-ostial left main (LM) imaging by frequency domain optical coherence tomography (FD-OCT). METHODS AND RESULTS We conducted a retrospective analysis of OCT studies performed to image lesions located in the non-ostial LM. OCT studies were analysed off-line to detect the number of artefact frames in the different LM/bifurcation segments. OCT cross-sectional images were used to assess area measures. OCT longitudinal reconstructions were used to obtain the LM length. Standard quantitative coronary angiography (QCA) was used as the reference methodology. A total of 54 patients with non-ostial LM disease entered the study. The mean number of LM artefact frames was 8±10, corresponding to 19% of the total number of LM frames analysed. The percentages of artefact frames differed significantly according to the segment analysed: 43.3% proximal LM, 11.4% mid LM and 2.1% distal LM, 2.0% ostial left anterior descending artery and 0% ostial left circumflex artery (p<0.0001). All LM OCT measurements were significantly correlated with QCA measurements. CONCLUSIONS The results of the present study show that FD-OCT assessment of non-ostial LM disease is feasible and may provide high-quality imaging. OCT assessment of distal LM is more efficient than that of the proximal LM segment.

Percutaneous management of vascular access in transfemoral transcatheter aortic valve implantation

Transcatheter aortic valve implantation (TAVI) using stent-based bioprostheses has recently emerged as a promising alternative to surgical valve replacement in selected patients. The main route for TAVI is retrograde access from the femoral artery using large sheaths (16-24 F). Vascular access complications are a clinically relevant issue in TAVI procedures since they are reported to occur in up to one fourth of patients and are strongly associated with adverse outcomes. In the present paper, we review the different types of vascular access site complications associated with transfemoral TAVI. Moreover, we discuss the possible optimal management strategies with particular attention to the relevance of early diagnosis and prompt treatment using endovascular techniques.

Biomarkers in Acute Coronary Syndrome

Background Evaluation of patients who present to the hospital with acute undifferentiated chest pain or other symptoms and signs suggestive of Acute Coronary Syndrome (ACS) is often a clinical challenge. The initial assessment, requiring a focused history (including risk factors analysis), a physical examination, an electrocardiogram (EKG) and serum cardiac marker determination, is time-consuming and troublesome. Recent investigations have indicated that increases in biomarkers of necrosis, inflammation, ischemia and myocardial stretch may provide earlier assessment of overall patient risk, help in identifying the adequate diagnostic and therapeutic management for each patient and allow for prevention of substantial numbers of new events. Approach and Content The purpose of this review is to provide an overview of the characteristics of several biomarkers that may have potential clinical utility to identify ACS patients. Patho-physiology, analytical and clinical characteristics have been evaluated for each marker, underlying the properties for potential routine clinical use. Summary The biomarkers discussed in this review are promising and might lead to improved diagnosis and risk stratification of patients with ACS, however their clinical application requires further studies. It is important to define their clinical role as diagnostic markers, their predictive value and the specificity, standardization and detection limits of the assays.

Endothelial progenitor cells, microvascular obstruction, and left ventricular remodeling in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention.

Endothelial progenitor cells (EPCs) are released from the bone marrow during cardiac ischemic events, potentially influencing vascular and myocardial repair. We assessed the clinical and angiographic correlates of EPC mobilization at the time of primary percutaneous coronary intervention in 78 patients with ST elevation myocardial infarction and the impact of both baseline and follow-up EPC levels on left ventricular (LV) remodeling. Blood samples were drawn from the aorta and the culprit coronary artery for cytofluorimetric EPC detection (CD34+CD45dimKDR+ cells, in percentage of cytofluorimetric counts). Area at risk was assessed by Bypass Angioplasty Revascularization Investigation myocardial jeopardy index, thrombotic burden as thrombus score and microvascular obstruction (MVO) as a combination of ST segment resolution and myocardial blush grade. Echocardiographic evaluation of LV remodeling was performed at 1-year follow-up in 54 patients, whereas peripheral EPC levels were reassessed in 40 patients. EPC levels during primary percutaneous coronary intervention were significantly higher in intracoronary than in aortic blood (0.043% vs 0.0006%, p <0.001). Both intracoronary and aortic EPC were related to area at risk extent, to intracoronary thrombus score (p <0.001), and inversely to MVO (p = 0.001). Peripheral EPC levels at 1-year follow-up were lower in patients with LV remodeling than in those without (0.001% [0.001 to 0.002] vs 0.003% [0.002 to 0.010]; p = 0.01) and independently predicted absence of remodeling at multivariate analysis. In conclusion, a rapid intracoronary EPC recruitment takes place in the early phases of ST elevation myocardial infarction, possibly reflecting an attempted reparative response. The extent of this mobilization seems to be correlated to the area at risk and to the amount of MVO. Persistently low levels of EPC are associated to LV remodeling.

Comparison of two- and three-dimensional quantitative coronary angiography to intravascular ultrasound in the assessment of intermediate left main stenosis.

Angiographic evaluation of intermediate left main coronary artery stenosis (LMS) is often limited. Three-dimensional (3D) quantitative coronary angiography has recently developed to overcome 2-dimensional (2D) quantitative coronary angiographic (QCA) limitations. In patients with angiographically intermediate LMS, we investigated whether 3D quantitative coronary angiography was superior to 2D quantitative coronary angiography in predicting the presence of a significant LMS, defined as a minimum luminal area <6 mm(2) at intravascular ultrasound (IVUS). 2D and 3D quantitative coronary angiography were compared in their measurements of minimum luminal area, percent area stenosis, minimum luminal diameter, and percent diameter stenosis and in their prediction of an IVUS minimum luminal area <6 mm(2). In total 58 target lesions were interrogated, 25 (43%) of which had an IVUS minimum luminal area <6 mm(2). Correlation between 3D-QCA minimum luminal area and IVUS minimum luminal area was stronger than the correlation between 2D-QCA minimum luminal area (or minimum luminal diameter) and IVUS minimum luminal area (R = 0.67, p = 0.0001, and R = 0.40, p = 0.001, respectively, p = 0.04 for comparison). To predict IVUS minimum luminal area <6 mm(2), the most accurate 2D-QCA measurement was minimum luminal diameter (area under curve 0.81, cutoff 2.2 mm, p = 0.0001), and the most accurate 3D-QCA measurement was minimum luminal area (area under curve 0.86, cutoff 5.6 mm(2), p = 0.0001). 2D-QCA percent diameter stenosis did not significantly predict IVUS minimum luminal area <6 mm(2) (area under curve 0.56, cutoff 38%, p = 0.45). In conclusion, the accuracy of quantitative coronary angiography in predicting LM IVUS minimum luminal area <6 mm(2) is limited. When IVUS is not available or contraindicated, 3D quantitative coronary angiography may assist in the evaluation of intermediate LMS. Among 2D-QCA parameters, minimum luminal diameter is more accurate than percent diameter stenosis in predicting significant LMS.

Association between inflammatory biomarkers and in-stent restenosis tissue features: an Optical Coherence Tomography Study

AIMS Inflammatory reaction after stent implantation is associated with in-stent restenosis (ISR). We assessed the association of optical coherence tomography (OCT) features of neointima with systemic levels of high-sensitivity C-reactive protein (hs-CRP) and eosinophil cationic protein (ECP) measured at the time of ISR detection. METHODS AND RESULTS Patients presenting with symptomatic angiographically documented ISR (diameter stenosis ≥ 50% by visual estimation) were included. Quantitative OCT analysis included the measurement of minimal lumen diameter, minimal luminal area, stent and neointimal area, stent and restenosis length, restenotic tissue burden, and symmetry ratio. Qualitative OCT analysis included the assessment of ISR plaque type, neointimal tissue structure, lumen shape, presence of microvessels and calcific nodules. At the time of ISR detection hs-CRP and ECP levels were measured, and statistical analysis was performed using as cut-off 3 mg/L and 4.5 µg/L, respectively. Our population included 40 patients, 24 bare metal stents and 16 drug-eluting stents. Patients with high hs-CRP levels had a higher restenostic tissue symmetry ratio (0.56 ± 0.17 vs. 0.42 ± 0.13, P = 0.01) when compared with patients with low hs-CRP levels. Patients with high ECP levels had a higher neointimal burden (70 ± 14 vs. 64 ± 11, P = 0.05) in comparison with patients with low ECP levels. CONCLUSIONS Inflammatory biomarkers assessed at the time of ISR detection are associated with different aspects of neointimal tissue. While hs-CRP seems to have a role in neointimal tissue shape, ECP is related to a neointimal burden.

Myeloperoxidase May Help to Differentiate Coronary Plaque Erosion From Plaque Rupture in Patients With Acute Coronary Syndromes

Coronary thrombosis is the most frequent final event leading to an acute coronary syndrome. In approximately two-thirds of cases, the thrombus overlies a ruptured plaque, whereas in one-third of cases it overlies an intact plaque with superficial endothelial erosion, a finding showed initially by histopathological postmortem studies and more recently confirmed by in vivo optical coherence tomography imaging. Interestingly, recent observations suggest that mechanisms leading to plaque rupture or erosion are different. In fact, in a recent study, we showed that myeloperoxidase levels in peripheral blood and expression within thrombi overlying the culprit plaque are much higher in patients with plaque erosion than in those with plaque rupture. These observations suggest that innate immunity activation is likely to play a key role, in particular, in plaque erosion and might become a therapeutic target in this subset of patients.

How to recognize endomyocardial fibrosis

Endomyocardial fibrosis is a disease of unknown cause, characterized by the development of restrictive cardiomyopathy. Although it is endemic in Africa, some cases have been described in Asia, South America and Europe, where a substantial unfamiliarity with this disease still exists. Moreover, differential diagnosis of endomyocardial fibrosis with other cardiomyopathies can be difficult, especially in asymptomatic patients and in initial stage of the disease. After initial echocardiographic analysis, the gold standard imaging technique is the cardiac magnetic resonance. Adjunctive diagnostic tools as endomyocardial biopsy can be considered in ambiguous cases and can help in patient management.