Primary thromboembolic prevention in multiple myeloma patients: An exploratory meta-analysis on aspirin use.

BACKGROUND: Multiple myeloma (MM) is a common hematological disorder, often complicated by venous thromboembolism, especially during treatment with immunomodulatory drugs. Acetylsalicylic acid (ASA) has been extensively used as thromboprophylaxis but its rationale is unclear and the efficacy versus low-molecular weight heparins (LMWH) is still matter of debate. European and American guidelines suggest different approaches and the optimal antithrombotic strategy is yet to be established. METHODS: We conducted an exploratory metanalysis and a systematic review on studies comparing ASA versus other interventions for thromboprophylaxis (no intervention or LMWH) in patients with MM. RESULTS: Ten studies were included (2 randomized controlled trials, 6 longitudinal and 2 retrospective studies) with 1,964 participants (1,257 treated with ASA, 640 with LMWH and 67 with no thromboprophylaxis). Patients treated with ASA had a significantly lower risk of VTE compared to no intervention (OR=0.20; 95%CI: 0.07-0.61, p=0.005; I2=41%). The use of ASA was associated with a higher VTE risk compared to LMWH in longitudinal studies (OR=2.60; 95%CI: 1.08-6.25; p=0.03; I2=0%), however no differences have been showed in randomized controlled trials. CONCLUSIONS: ASA demonstrated a good efficacy compared to no intervention; data are insufficient to confirm superiority of LMWH over ASA as thromboprophylaxis in MM patients. Large and well powered trials are warranted.

RANKL Expression Is Increased in Circulating Mononuclear Cells of Patients with Calcific Aortic Stenosis.

We aimed to investigate whether the expression of the OPG/RANK/RANKL triad in peripheral blood mononuclear cells (PBMC) and circulating levels of markers of ectopic mineralization (OPG, FGF-23, PPi) are modified in patients with calcific aortic valve disease (CAVD). We found that patients affected by CAVD (n = 50) had significantly higher circulating levels of OPG as compared to control individuals (p = 0.003). No differences between the two groups were found in FGF-23 and PPi levels. RANKL expression was higher in the PBMC from CAVD patients (p = 0.018) and was directly correlated with the amount of valve calcification (p = 0.032). In vitro studies showed that treatment of valve interstitial cells (VIC) with RANKL plus phosphate was followed by increase in matrix mineralization (p = 0.001). In conclusion, RANKL expression is increased in PBMC of patients with CAVD, is directly correlated with the degree of valve calcification, and promotes pro-calcific differentiation of VIC.

Cardio-oncology: the role of advanced echocardiography in cancer patients.

INTRODUCTION: Cardio-oncology is a rapidly growing field aimed at improving the quality of care of cancer patients by preventing and monitoring cardiovascular complications resulting from cancer treatment. Cardiac imaging, and in particular, transthoracic echocardiography, plays an essentialrole in the baseline assessment and serial follow-up of cardio-oncology patients. Areas covered: This review article discusses the role of cardiac imaging with a focus on advanced echocardiography for the detection and management of cancer therapy related cardiovascular complications, in particular, left ventricular dysfunction and heart failure. Expert commentary: While traditional imaging based assessment of left ventricular ejection fraction still has its place in cardiac monitoring, more advanced echocardiographic modalities, in particular, myocardial deformation imaging with speckle tracking strain analysis, show great potential for detecting early signs of cardiotoxicity. Larger studies are needed to determine both the clinical role of strain measurement in influencing initiation of cardioprotective agents and its prognostic value in long term outcome.

European Association of Cardiovascular Imaging/Cardiovascular Imaging Department of the Brazilian Society of Cardiology recommendations for the use of cardiac imaging to assess and follow patients after heart transplantation.

The cohort of long-term survivors of heart transplant is expanding, and the assessment of these patients requires specific knowledge of the surgical techniques employed to implant the donor heart, the physiology of the transplanted heart, complications of invasive tests routinely performed to detect graft rejection (GR), and the specific pathologies that may affect the transplanted heart. A joint EACVI/Brazilian cardiovascular imaging writing group committee has prepared these recommendations to provide a practical guide to echocardiographers involved in the follow-up of heart transplant patients and a framework for standardized and efficient use of cardiovascular imaging after heart transplant. Since the transplanted heart is smaller than the recipient's dilated heart, the former is usually located more medially in the mediastinum and tends to be rotated clockwise. Therefore, standard views with conventional two-dimensional (2D) echocardiography are often difficult to obtain generating a large variability from patient to patient. Therefore, in echocardiography laboratories equipped with three-dimensional echocardiography (3DE) scanners and specific expertise with the technique, 3DE may be a suitable alternative to conventional 2D echocardiography to assess the size and the function of cardiac chambers. 3DE measurement of left (LV) and right ventricular (RV) size and function are more accurate and reproducible than conventional 2D calculations. However, clinicians should be aware that cardiac chamber volumes obtained with 3DE cannot be compared with those obtained with 2D echocardiography. To assess cardiac chamber morphology and function during follow-up studies, it is recommended to obtain a comprehensive echocardiographic study at 6 months from the cardiac transplantation as a baseline and make a careful quantitation of cardiac chamber size, RV systolic function, both systolic and diastolic parameters of LV function, and pulmonary artery pressure. Subsequent echocardiographic studies should be interpreted in comparison with the data obtained from the 6-month study. An echocardiographic study, which shows no change from the baseline study, has a high negative predictive value for GR. There is no single systolic or diastolic parameter that can be reliably used to diagnose GR. However, in case several parameters are abnormal, the likelihood of GR increases. When an abnormality is detected, careful revision of images of the present and baseline study (side-by-side) is highly recommended. Global longitudinal strain (GLS) is a suitable parameter to diagnose subclinical allograft dysfunction, regardless of aetiology, by comparing the changes occurring during serial evaluations. Evaluation of GLS could be used in association with endomyocardial biopsy (EMB) to characterize and monitor an acute GR or global dysfunction episode. RV size and function at baseline should be assessed using several parameters, which do not exclusively evaluate longitudinal function. At follow-up echocardiogram, all these parameters should be compared with the baseline values. 3DE may provide a more accurate and comprehensive assessment of RV size and function. Moreover, due to the unpredictable shape of the atria in transplanted patients, atrial volume should be measured using the discs' summation algorithm (biplane algorithm for the left atrium) or 3DE. Tricuspid regurgitation should be looked for and properly assessed in all echocardiographic studies. In case of significant changes in severity of tricuspid regurgitation during follow-up, a 2D/3D and colour Doppler assessment of its severity and mechanisms should be performed. Aortic and mitral valves should be evaluated according to current recommendations. Pericardial effusion should be serially evaluated regarding extent, location, and haemodynamic impact. In case of newly detected pericardial effusion, GR should be considered taking into account the overall echocardiographic assessment and patient evaluation. Dobutamine stress echocardiography might be a suitable alternative to routine coronary angiography to assess cardiac allograft vasculopathy (CAV) at centres with adequate experience with the methodology. Coronary flow reserve and/or contrast infusion to assess myocardial perfusion might be combined with stress echocardiography to improve the accuracy of the test. In addition to its role in monitoring cardiac chamber function and in diagnosis the occurrence of GR and/or CAV, in experienced centres, echocardiography might be an alternative to fluoroscopy to guide EMB, particularly in children and young women, since echocardiography avoids repeated X-ray exposure, permits visualization of soft tissues and safer performance of biopsies of different RV regions. Finally, in addition to the indications about when and how to use echocardiography, the document also addresses the role of the other cardiovascular imaging modalities during follow-up of heart transplant patients. In patients with inadequate acoustic window and contraindication to contrast agents, pharmacological SPECT is an alternative imaging modality to detect CAV in heart transplant patients. However, in centres with adequate expertise, intravascular ultrasound (IVUS) in conjunction with coronary angiography with a baseline study at 4-6 weeks and at 1 year after heart transplant should be performed to exclude donor coronary artery disease, to detect rapidly progressive CAV, and to provide prognostic information. Despite the fact that coronary angiography is the current gold-standard method for the detection of CAV, the use of IVUS should also be considered when there is a discrepancy between non-invasive imaging tests and coronary angiography concerning the presence of CAV. In experienced centres, computerized tomography coronary angiography is a good alternative to coronary angiography to detect CAV. In patients with a persistently high heart rate, scanners that provide high temporal resolution, such as dual-source systems, provide better image quality. Finally, in patients with insufficient acoustic window, cardiac magnetic resonance is an alternative to echocardiography to assess cardiac chamber volumes and function and to exclude acute GR and CAV in a surveillance protocol.

Antiphospholipid syndrome and the heart: a case series and literature review.

Antiphospholipid syndrome is a rare autoimmune disease characterized by a high tendency of developing thrombotic events. It is diagnosed in the presence of specific laboratory criteria (positivity for lupus anticoagulant, and the presence of anticardiolipin and aß2GPI antibodies) and clinical criteria such as thrombosis in any district (arterial or venous) and pregnancy morbidity. Being a multisystem disease, the heart is commonly affected by direct (autoimmune mediated action) or indirect (thrombosis) pathological mechanisms. Heart valve lesions are the most frequent manifestations; however, the haemodynamic significance is quite uncommon but when it occurs it may require surgery that further complicates the picture due to the high risk of thrombosis. Coronary arteries and myocardium are also affected leading to ischaemic heart disease and left ventricular dysfunction. Other findings include chronic thromboembolic pulmonary hypertension and accelerated atherosclerosis. The consequences of heart involvement may be significant in overt disease. The treatment of cardiac complications is challenging and requires an in-depth knowledge of the disease.

Clones of interstitial cells from bovine aortic valve exhibit different calcifying potential when exposed to endotoxin and phosphate.

OBJECTIVE: Our purpose was to study in vitro whether phenotypically-distinct interstitial cell clones from bovine aortic valve (BVIC) possess different calcifying potential in response to endotoxin (lipopolysaccharide [LPS]) and phosphate (Pi). METHODS AND RESULTS: Among various clones of BVIC obtained by limited dilution technique we selected 4 clones displaying different growth patterns and immunophenotypes. Uncloned and cloned cells were treated with combinations of LPS (100 ng/mL) and Pi (2.4 mmol/L). Uncloned BVIC showed increased alkaline phosphatase activity (ALP) after treatment with LPS, which resulted in calcification after addition of Pi. Among BVIC clones, only Clone 1 (fibroblast-like phenotype) showed a relevant increase in ALP after LPS treatment in parallel with prevention of smooth muscle (SM) alpha-actin accumulation. No effect was observed in clonal cells harboring a more stable SM cell-like profile (Clone 4). None of the isolated clones calcified but mineralization was induced in the presence of LPS plus Pi when Clone 1 was cocultured with Clone 4 or after seeding on type I collagen sponges. CONCLUSIONS: Endotoxin and phosphate can act as valve calcification promoters by targeting specific fibroblast-like interstitial valve cells that possess a unique procalcific potential.

Critical role of macrophages in glucocorticoid driven vascular calcification in a mouse-model of atherosclerosis.

OBJECTIVE: Macrophage-derived products are known to play a crucial role during atherogenesis and vascular calcification. Glucocorticoids (GC) are important modulators of immune cell functions, but their specific effects on macrophages behavior during plaque formation are not defined. The present study was therefore designed to investigate the effects of macrophage-specific deletion of the glucocorticoid receptor (GR(LysMCre)) on atherogenesis and vascular calcification in a hyperlipidemic mouse-model. METHODS AND RESULTS: Bone marrow was isolated from GR(LysMCre) mice and wild-type controls (GR(flox)) and subsequently transplanted into lethally irradiated LDL-receptor-deficient mice. Animals were fed a Western-type diet for 15 or 24 weeks, and atherosclerotic lesions within the aortic sinus were evaluated. At both time points, no significant difference in serum lipid and corticosterone concentrations, atherosclerotic lesion size and macrophage-content within the lesions could be observed. However, GR(LysMCre) mice showed less calcification as well as a significant reduction of RANKL, BMP2, and Msx2 expression within the vasculature. In vitro studies using conditioned media from macrophages which had been stimulated with dexamethasone demonstrated a dose-dependent increase in calcium deposition by vascular smooth muscle cells. CONCLUSIONS: This study demonstrates that macrophage-specific glucocorticoid receptor inactivation reduces vascular calcification without affecting atherosclerotic lesion size in LDL receptor-deficient mice.