Failed Downregulation of Circulating MicroRNA-155 in the Early Phase after ST Elevation Myocardial Infarction Is Associated with Adverse Left Ventricular Remodeling.

BACKGROUND: MicroRNA are noncoding RNA that have a significant role in both inflammatory and cardiovascular diseases. AIMS: We aimed to assess whether the inflammation-related microRNA-155 is associated with the development of adverse left ventricular (LV) remodeling following ST elevation myocardial infarction (STEMI). METHODS: Peripheral blood samples were collected in the inflammatory (day 2), proliferative (day 5), and maturation phases (6 months) after STEMI (n = 20). Granulocytes, monocytes, and lymphocytes were enumerated with flow cytometry. The changes in LV volumes were assessed with 3-D echocardiography on day 1 and after 6 months. Adverse remodeling was defined as a >20% increase in end-diastolic volume. Healthy subjects were recruited as controls. RESULTS: MicroRNA-155 measured on day 5 correlated positively with the relative change in end-diastolic volume (ρ = 0.490, p = 0.028). MicroRNA-155 (day 5) was significantly higher in patients with compared to patients without adverse LV remodeling. The expression level was similar in healthy subjects (n = 8) and in patients with LV remodeling. There was a positive correlation between microRNA-155 and the amount of monocytes (day 5, ρ = 0.463, p = 0.046). CONCLUSION: Impaired downregulation of microRNA-155 during the second phase of the post- STEMI inflammatory response is a determinant of the development of adverse LV remodeling.

Altered expression of monocyte and dendritic cell membrane-associated antigens following coronary angiography.

INTRODUCTION: Coronary angiography is able to induce a systemic inflammatory response. We hypothesised that this procedure may affect monocyte and dendritic cell count and membrane-associated antigen expression. METHODS: Blood samples were obtained before and immediately after coronary angiography in twenty patients with stable angina pectoris. Cell enumeration and antigen expression levels were evaluated by flow cytometry. Plasma levels of soluble CD14 and interleukin-6 were quantified by ELISA. RESULTS: The absolute and relative numbers of circulating monocytes (Mon1, Mon2 and Mon3 subsets) and dendritic cells (myeloid and plasmacytoid subsets) were not significantly different pre-versus post-angiography. Expression of CD14 on Mon1 and Mon2 decreased significantly by 12.01% (P = 0.002) and 13.01% (P=0.012), respectively. CD16 expression on Mon2 (+10.53%; P=0.017) and Mon3 (+12.58%; P<0.001) increased. CD45 expressed by monocytic and dendritic cells was lowered (-5.80% and P = 0.001, -11.49% and P < 0.001, respectively). The level of plasma IL-6 decreased significantly (P = 0.002). The reduction in sCD14 was not significant (P = 0.054). CONCLUSION: Coronary angiography leads to changes in surface expression of CD14, CD16 and CD45. These findings underline the importance of blood collection prior to the angiographic procedure when aiming to study the functional analysis of monocyte and dendritic cell numbers by flow cytometry.

Preprocedural CT evaluation of transcatheter aortic valve replacement: what the radiologist needs to know.

Aortic valve stenosis is the most common valvular heart disease in the Western world. When symptomatic, aortic valve stenosis is a debilitating disease with a dismal short-term prognosis, invariably leading to heart failure and death. Elective surgical valve replacement has traditionally been considered the standard of care for symptomatic aortic valve stenosis. However, several studies have identified various subgroups of patients with a significantly elevated risk for surgery-related complications and death. Thus, not every patient is a suitable candidate for surgery. Recent developments in transcatheter-based therapies have provided an alternative therapeutic strategy for the nonsurgical patient population known as transcatheter aortic valve replacement (TAVR) (also called transcatheter aortic valve implantation or percutaneous aortic valve replacement). In TAVR, the native aortic valve is replaced with a bioprosthetic valve via a nonsurgical endovascular, transaortic, or transapical pathway. Nevertheless, several anatomic and technical criteria must be met to safeguard patient eligibility and procedural success. Therefore, noninvasive imaging plays a crucial role in both patient selection and subsequent matching to a specific transcatheter valve size in an effort to ensure accurate prosthesis deployment and minimize peri- and postprocedural complications. The authors review the relevant anatomy of the aortic root, emphasizing the implications of anatomic pitfalls for correct reporting of imaging-derived measurements and important differences between findings obtained with different imaging modalities. They also discuss the evolving role of computed tomography and the role of the radiologist in patient triage in light of current viewpoints regarding patient selection, device size selection, and the preprocedural evaluation of possible access routes. Online supplemental material is available for this article.

Transcatheter aortic valve replacement: postoperative CT findings of Sapien and CoreValve transcatheter heart valves.

Transcatheter aortic valve replacement represents one of the most exciting medical technical developments in recent years, offering a much-needed therapeutic alternative for patients with severe aortic valve stenosis who, due to comorbidities and advanced age, are considered to be inoperable or at high surgical risk. The efficacy of this procedure compared with standard surgical intervention has been properly validated in multicenter randomized controlled trials (PARTNER A and B trials), leading to widespread clinical implementation, with over 50,000 procedures currently being performed worldwide each year. Although much of the attention has rightly focused on the potential role of computed tomography (CT) in the preprocedural assessment of the aortic root and the establishment of imaging-guided valve-sizing algorithms, less is known regarding the postprocedural CT characteristics of transcatheter heart valves (THVs). However, given the increasing worldwide recognition and clinical implementation of these devices, they will no doubt be encountered with increasing frequency in patients referred for thoracic CT, either for postprocedural evaluation of the aortic root or for unrelated reasons. Familiarity with these devices and their CT characteristics will increase diagnostic confidence and the value of the radiology report. The authors describe the physical and imaging properties of the currently commercially available THVs, their normal postprocedural imaging appearances, and potential complications that can be detected at CT. In addition, they discuss the relative strengths and weaknesses of CT and echocardiography in this setting.

Automated mitral valve assessment for transcatheter mitral valve replacement planning.

Transcatheter mitral valve replacement (TMVR) has emerged as a minimally invasive alternative for treating patients suffering from mitral valve disease. The number of TMVR procedures is expected to rise as devices currently in clinical trials obtain approval for commercialization. Automating the planning of such interventions becomes, therefore, more relevant in an attempt to decrease inter-subject discrepancies and time spent in patient assessment. This study evaluates the performance of an automated method for detection of anatomical landmarks and generation of relevant measurements for device selection and positioning. Cardiac CT scans of 70 patients were collected retrospectively. Fifty scans were used to generate a statistical shape model (SSM) of the left heart chambers at ten different timepoints, whereas the remaining 20 scans were used for validation of the automated method. The clinical measurements resulting from the anatomical landmarks generated automatically were compared against the measurements obtained through the manual indication of the corresponding landmarks by three observers, during systole and diastole. The automatically generated measurements were in close agreement with the user-driven analysis, with intraclass correlation coefficients (ICC) consistently lower for the saddle-shaped (ICCArea = 0.90, ICCPerimeter 2D = 0.95, ICCPerimeter 3D = 0.93, ICCAP-Diameter = 0.71, ICCML-Diameter = 0.90) compared to the D-shaped annulus (ICCArea = 0.94, ICCPerimeter 2D = 0.96, ICCPerimeter 3D = 0.96, ICCAP-Diameter = 0.95, ICCML-Diameter = 0.92). The larger differences observed for the saddle shape suggest that the main discrepancies occur in the aorto-mitral curtain. This is supported by the fact that statistically significant differences are observed between the two annulus configurations for area (p < 0.001), 3D perimeter (p = 0.009) and AP diameter (p < 0.001), whereas errors for 2D perimeter and ML diameter remained almost constant. The mitral valve center deviated in average 2.5 mm from the user-driven position, a value comparable to the inter-observer variability. The present study suggests that accurate mitral valve assessment can be achieved with a fully automated method, what could result in more consistent and shorter pre-interventional planning of TMVR procedures.

CT imaging features of atrioventricular shunts: what the radiologist must know.

UNLABELLED: In the last decade, cardiac computed tomography (CT) has gained mainstream acceptance for the noninvasive exclusion of significant coronary disease in a selected population. Improvements in electrocardiogram (ECG)-triggered imaging techniques also allow, by extension, a proper evaluation of the complete heart anatomy. Given the increasing worldwide clinical implementation of cardiac CT for coronary artery evaluation, radiologists can, incidentally, be confronted with unfamiliar and previously unsuspected non-coronary cardiac pathologies, including congenital morphological defects. This presence of congenital heart disease (CHD) should not be overlooked, being the most common form of birth defect, with a total birth prevalence of 9.1 per 1000 live births worldwide [1]. The prevalence of adult patients with CHD is estimated to be 3000 per million adults [2]. Ventricular septal defects (VSDs) are the most frequent subtypes of CHD, accounting together with atrial septal defects (ASDs) for nearly half of all CHD cases [1]. While some small defects are rarely symptomatic and can go undetected for life, others are clinically significant and require adequate and timely medical intervention. In this article, we present the CT imaging features of atrioventricular (AV) shunts, highlighting both their embryological origins and associated relevant clinical features. TEACHING POINTS: • Congenital heart disease (CHD) is the most common birth defect. • Ventricular and atrial septal defects account for nearly half of CHD cases. • Atrioventricular defects can frequently be detected on a cardiac CT. • Radiologists must be able to identify clinically significant atrioventricular defects.

The cellular immune system in the post-myocardial infarction repair process.

Growing evidence indicates that overactivation and prolongation of the inflammatory response after acute myocardial infarction (AMI) result in worse left ventricular remodelling, dysfunction and progression to heart failure. This post-AMI inflammatory response is characterised by the critical involvement of cells from both the innate and adaptive immune systems. In this review paper, we aim to summarise and discuss the emergence of immune cells in the bloodstream and myocardium after AMI in men and mice. Subset composition, phenotypes, and kinetics of immune cells are considered. In addition, the relation with post-MI cardiac remodelling, function and outcome is reported. Increased knowledge of immune components, the mechanisms and interactions by which these cells contribute to myocardial damage and repair following AMI may help to close the gaps that limit improvement of treatments of those who survive the acute infarction.

Management of cardiogenic shock complicating acute myocardial infarction.

Cardiogenic shock complicates approximately 5-10% of cases with acute myocardial infarction and carries a poor prognosis. Early revascularization remains the cornerstone treatment of cardiogenic shock complicating myocardial infarction. Inotropic and/or vasopressor agents can be used for haemodynamic stabilization, although this comes at the expense of increased myocardial oxygen consumption and extended myocardial ischaemia. In recent years, the use of mechanical circulatory support has significantly increased. However, there is only limited data available from randomized trials evaluating the different percutaneous support systems. This review summarizes the available literature concerning the management of cardiogenic shock and gives an overview of the recommendations of the European and German-Austrian guidelines on cardiogenic shock.

Influence of zero flow pressure on fractional flow reserve.

Fractional flow reserve (FFR) is a commonly used index to assess the functional severity of a coronary artery stenosis. It is conventionally calculated as the ratio of the pressure distal (Pd) and proximal (Pa) to the stenosis (FFR= Pd/Pa). We hypothesize that the presence of a zero flow pressure (Pzf), requires a modification of this equation. Using a dynamic hydraulic bench model of the coronary circulation, which allows one to incorporate an adjustable Pzf, we studied the relation between pressure-derived FFR = Pdo/Pa, flow-derived true FFRQ = Qs/QN (= ratio of flow through a stenosed vessel to flow through a normal vessel), and the corrected pressure-derived FFRc = (Pd-Pzf)/(Pa-Pzf) under physiological aortic pressures (70 mmHg, 90 mmHg, and 110 mmHg). Imposed Pzf values varied between 0 mmHg and 30 mmHg. FFRc was in good agreement with FFRQ, whereas FFR consistently overestimated FFRQ. This overestimation increased when Pzf increased, or when Pa decreased, and could be as high as 56% (Pzf=30 mmHg and Pa =70 mmHg). According to our experimental study, calculating the corrected FFRC instead of FFR, if Pzf is known, provides a physiologically more accurate evaluation of the functional severity of a coronary artery stenosis.

Left ventricular twist during dobutamine stress echocardiography after acute myocardial infarction: association with reverse remodeling.

Left ventricular (LV) twist is emerging as a marker of global LV contractility after acute myocardial infarction (AMI). This study aimed to describe stress-induced changes in LV twist during dobutamine stress echocardiography (DSE) after AMI and investigate their association with LV reverse remodeling at 6 months follow-up. In 82 consecutive first AMI patients (61 ± 12 years, 85 % male) treated with primary percutaneous coronary intervention, DSE was performed at 3 months follow-up. Two-dimensional speckle-tracking-derived apical and basal rotation and LV twist were calculated at rest, low- and peak-dose stages. LV reverse remodeling was defined as ≥10 % decrease in LV end-systolic volume between baseline and 6 months follow-up. Patterns of LV twist response on DSE consisted of either a progressive increase throughout each stage (n = 18), an increase at either low- or peak-dose (n = 53) or no significant increase (n = 11). LV reverse remodeling occurred in 28 (34 %) patients, who showed significantly higher peak-dose LV twist (8.51° vs. 6.69°, p = 0.03) and more frequently progressive LV twist increase from rest to peak-dose (39 vs. 13 %, p < 0.01) compared to patients without reverse remodeling. Furthermore, increase in LV twist from rest to peak-dose was the only independent predictor of LV reverse remodeling at 6 months follow-up (OR 1.3, 95 % CI 1.1-1.5, p = 0.005). Both the pattern of progressive increase in LV twist and the stress-induced increment in LV twist on DSE are significantly associated with LV reverse remodeling at 6 month follow-up after AMI, suggesting its potential use as a novel marker of contractile reserve.

Transesophageal echocardiography for cardiac thromboembolic risk assessment in patients with severe, symptomatic aortic valve stenosis referred for potential transcatheter aortic valve implantation.

Stroke is a devastating complication after transcatheter aortic valve implantation (TAVI) and might partially be related to cardiac embolization. The aim of this single-center prospective study was to determine the incidence of intracardiac thrombi and left atrial spontaneous echo contrast (SEC), both known predictors of cardiac embolic stroke, in patients referred for potential TAVI. One hundred four consecutive patients with severe symptomatic aortic valve stenosis and at high or very high risk for surgery were included and underwent transesophageal echocardiography. In 11 patients (10.6%), intracardiac thrombi were detected, and 25 patients (24%) showed dense grade 2 SEC. Atrial fibrillation (p <0.0001), diastolic dysfunction (p = 0.0005), and atrial size (p = 0.0038) were related to the presence of intracardiac thrombus and/or dense SEC on multivariate analysis. In conclusion, the incidence of intracardiac thrombi and dense SEC in (very) high-risk patients with severe aortic valve stenosis referred for potential TAVI is high and can accurately be detected using transesophageal echocardiography. Systematic thromboembolic evaluation using transesophageal echocardiography is thus recommended in patients referred for TAVI.

Comparison of magnetic resonance imaging of aortic valve stenosis and aortic root to multimodality imaging for selection of transcatheter aortic valve implantation candidates.

The purpose of the present study was to compare the aortic valve area, aortic valve annulus, and aortic root dimensions measured using magnetic resonance imaging (MRI) with catheterization, transthoracic echocardiography (TTE), and transesophageal echocardiography (TEE). An optimal prosthesis--aortic root match is an essential goal when evaluating patients for transcatheter aortic valve implantation. Comparisons between MRI and the other imaging techniques are rare and need validation. In 24 consecutive, high-risk, symptomatic patients with severe aortic stenosis, aortic valve area was prospectively determined using MRI and direct planimetry using three-dimensional TTE and calculated by catheterization using the Gorlin equation and by Doppler echocardiography using the continuity equation. Aortic valve annulus and the aortic root dimensions were prospectively measured using MRI, 2-dimensional TTE, and invasive aortography. In addition, aortic valve annulus was measured using TEE. No differences in aortic valve area were found among MRI, Doppler echocardiography, and 3-dimensional TTE compared with catheterization (p = NS). Invasive angiography underestimated aortic valve annulus compared with MRI (p <0.001), TEE (p <0.001), and 2-dimensional TTE (p <0.001). Two-dimensional TTE tended to underestimate the aortic valve annulus diameters compared to TEE and MRI. In contrast to 2-dimensional TTE, 3 patients had aortic valve annulus beyond the transcatheter aortic valve implantation range using TEE and MRI. In conclusion, MRI planimetry, Doppler, and 3-dimensional TTE provided an accurate estimate of the aortic valve area compared to catheterization. MRI and TEE provided similar and essential assessment of the aortic valve annulus dimensions, especially at the limits of the transcatheter aortic valve implantation range.

Implications of antibodies to heat-shock proteins in ischemic heart disease.

OBJECTIVE: Experimental studies illustrate that priming with infectious agents, like Chlamydia pneumoniae, is involved in plaque formation and progression based on molecular mimicry with host heat-shock proteins (HSP). We have here evaluated the hypothesis that C. pneumoniae contributes to atherosclerotic disease progression via anti-HSP antibodies. METHODS: The blood circulation of 151 consecutive patients with ischemic heart disease was screened for antibodies against human and Chlamydia HSP60 and C. pneumoniae IgG. Antibody levels were associated with the angiographic extent of coronary atherosclerosis, with clinical symptoms of ischemic heart disease and with biochemical and functional endothelial dysfunction markers. RESULTS: Positive serology to human (11%) or Chlamydia HSP60 (22%) was not associated with the presence and extent of atherosclerosis, neither was it related with endothelial dysfunction. Patients with acute myocardial infarction had significantly lower Chlamydia HSP60 antibody levels (median OD 0.12, range: 0.02-0.75) than patients with stable (median OD 0.22, range: 0.02-2.67) or unstable angina pectoris (median OD 0.24, range: 0-2.48) (p=0.032). Subjects with positive C. pneumoniae IgG serology (if measured at a titre of 1:128) showed reduced flow-mediated vasodilation (p=0.024), but vasodilation responses did not differ in single-, two- or three-vessel disease. CONCLUSION: Overall, antibody responses to C. pneumoniae IgG, human or Chlamydia HSP60 are not associated with endothelial dysfunction and presence and severity of coronary artery disease, arguing against the suggestion that infection contributes to disease progression and supplying additional proof that C. pneumoniae is an unlikely major risk factor of coronary atherosclerosis.

Quantitative coronary arteriography on digital flat-panel system.

On images acquired with a digital flat-panel (DFP) detector, known for its better image quality, the performance of a validated quantitative coronary arteriography (QCA) software, CAASII (Cardiovascular Angiography Analysis System or CAAS), and a DFP-dedicated QCA algorithm (flat-panel analysis software or FPAS) was compared in a phantom and a patient study. On phantom, FPAS performed with higher accuracy the quantification of the smallest tubes and the calibration of an empty catheter. The overall accuracy and precision for the quantification procedure was better for FPAS (0.07 +/- 0.04 mm) than for the CAAS (0.19 +/- 0.06 mm; P = 0.03 and P < 0.01, respectively). In the patient study, the main difference between the two algorithms was found in the small diameters: CAAS almost always gave higher values than FPAS for the minimal luminal diameter (P < 0.001) and could only give values up to 70% for diameter stenosis. In conclusion, the FPAS can be considered more appropriate for assessing severe stenoses on digital flat-panel images.