Are We Up to Speed? From Big Data to Rich Insights in CV Imaging for a Hyperconnected World

Plaques d'acer corten en homenatge a les actrius que han guanyat el Premi Memorial Margarida Xirgu de diferents anys; ubicades a la Pl. Margarida Xirgu corresponen a la col·lecció Institut del Teatre

Noninvasive Molecular Imaging of Disease Activity in Atherosclerosis.

Major focus has been placed on the identification of vulnerable plaques as a means of improving the prediction of myocardial infarction. However, this strategy has recently been questioned on the basis that the majority of these individual coronary lesions do not in fact go on to cause clinical events. Attention is, therefore, shifting to alternative imaging modalities that might provide a more complete pan-coronary assessment of the atherosclerotic disease process. These include markers of disease activity with the potential to discriminate between patients with stable burnt-out disease that is no longer metabolically active and those with active atheroma, faster disease progression, and increased risk of infarction. This review will examine how novel molecular imaging approaches can provide such assessments, focusing on inflammation and microcalcification activity, the importance of these processes to coronary atherosclerosis, and the advantages and challenges posed by these techniques.M.R.D and D.E.N are supported by the British Heart Foundation (CH/09/002 to D.E.N., FS/14/78/31020 to M.R.D). M.R.D is the recipient of the Sir Jules Thorn Biomedical Research Award 2015 (M.R.D.) E.A. research is supported by R01HL 114805 and R01HL 109506.This is the final version of the article. It first appeared from Lippincott, Williams & Wilkins via http://dx.doi.org/10.1161/CIRCRESAHA.116.30797

Spasmogenic Effects of the Proteasome Inhibitor Carfilzomib on Coronary Resistance, Vascular Tone and Reactivity

Background: Carfilzomib (CFZ) is a new proteasome inhibitor used for the treatment of multiple myeloma. Besides heart failure, angina and myocardial ischemia occurred following administration of CFZ, which is not contraindicated in patients with recent myocardial infarction/unstable angina excluded from the safety trials. Aimof Study: To test the effects of CFZ (10−9 to 10−7 mol/L) on vascular tone and reactivity in the isolated rabbit heart and aorta. Methods and Results: CFZ administered by bolus injection to the isolated heart increased coronary perfusion pressure (CPP) at all tested concentrations and mildly raised left ventricular pressure and heart rate, only at the highest concentration. Addition of CFZ directly into the organ bath increased the basal tone of isolated aortic strips with contraction plateau reached after 10 min. This spasmogenic effect doubled following ablation of the endothelium. Pretreatment with CFZ amplified the vasospastic action exerted by KCl, noradrenaline (NA) and angiotensin II (A) on aortic strips, and impaired vasodilation following administration of nitroglycerin (NTG) and nifedipine (NFP) on the contraction plateau induced by KCl, NA and A. Aortic strips pretreatedwith CFZ exhibited impaired relaxation, as compared to untreated strips, following administration of acetylcholine (Ach), an endothelium- dependent vasodilating agent, on the plateau of NA contraction (p b 0.05). Conclusions: CFZ increased CPP, resting vasoconstricting tone and the spasmogenic effect of different agents. Preincubation with CFZ decreased the anti-spasmogenic activity of NTG and NFP, as well as reduced by over 50% the vasodilating effect of Ach, suggesting that CFZ can impair vasodilation via an endothelium dependent mechanism. Further studies are warranted to establish its clinical safety in patients with known CAD and prior history of coronary spasm

Trends in Coronary Heart Disease Epidemiology in India

Cardiovascular diseases, especially coronary heart disease (CHD), are epidemic in India. The Registrar General of India reported that CHD led to 17% of total deaths and 26% of adult deaths in 2001-2003, which increased to 23% of total and 32% of adult deaths in 2010-2013. The World Health Organization (WHO) and Global Burden of Disease Study also have highlighted increasing trends in years of life lost (YLLs) and disability-adjusted life years (DALYs) from CHD in India. In India, studies have reported increasing CHD prevalence over the last 60 years, from 1% to 9%-10% in urban populations and <1% to 4%-6% in rural populations. Using more stringent criteria (clinical ± Q waves), the prevalence varies from 1%-2% in rural populations and 2%-4% in urban populations. This may be a more realistic prevalence of CHD in India. Case-control studies have reported that important risk factors for CHD in India are dyslipidemias, smoking, diabetes, hypertension, abdominal obesity, psychosocial stress, unhealthy diet, and physical inactivity. Suitable preventive strategies are required to combat this epidemic

Concomitant Cardiac Amyloidosis in Severe Aortic Stenosis: The Trojan Horse?

peer reviewe

Decreased expression of Klotho in cardiac atria biopsy samples from patients at higher risk of atherosclerotic cardiovascular disease

Background. Klotho proteins (α- and β) are membrane-based circulating proteins that regulate cell metabolism, as well as the lifespan modulating activity of Fibroblast Growth Factors. Recent data has shown that higher plasma circulating Klotho levels reduce cardiovascular risk, suggesting Klotho has a protective role in cardiovascular diseases. However, although so far it has been identified in various organs, it is unknown whether cardiomyocytes express Klotho and Fibroblast Growth Factors(FGFs), and whether high cardiovascular risk could affect cardiac expression of Klotho, FGFs and other molecules. Methods. We selected 20 patients with an estimated 10-year high atherosclerotic cardiovascular disease and 10 age-matched control subjects with an estimated 10-year low risk undergone cardiac surgery for reasons other than coronary artery by-pass. In myocardial biopsies, we evaluated by immuno-histochemistry whether Klotho and FGFs were expressed in cardiomyocytes, and whether higher cardiovascular risk influenced the expression of other molecules involved in endoplasmic reticulum stress, oxidative stress, inflammation and fibrosis. Results. Only cardiomyocytes of patients with a higher cardiovascular risk showed lower expression of Klotho, but higher expressions of FGFs. Furthermore, higher cardiovascular risk was associated with increased expression of oxidative and endoplasmic reticular stress, inflammation and fibrosis. Conclusions. This study showed for the first time that Klotho proteins are expressed in human cardiomyocytes and that cardiac expression of Klotho is down-regulated in higher cardiovascular risk patients, while expression of stress-related molecules were significantly increased

Machine Learning Framework to Identify Individuals at Risk of Rapid Progression of Coronary Atherosclerosis: From the PARADIGM Registry.

Background Rapid coronary plaque progression (RPP) is associated with incident cardiovascular events. To date, no method exists for the identification of individuals at risk of RPP at a single point in time. This study integrated coronary computed tomography angiography-determined qualitative and quantitative plaque features within a machine learning (ML) framework to determine its performance for predicting RPP. Methods and Results Qualitative and quantitative coronary computed tomography angiography plaque characterization was performed in 1083 patients who underwent serial coronary computed tomography angiography from the PARADIGM (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging) registry. RPP was defined as an annual progression of percentage atheroma volume ≥1.0%. We employed the following ML models: model 1, clinical variables; model 2, model 1 plus qualitative plaque features; model 3, model 2 plus quantitative plaque features. ML models were compared with the atherosclerotic cardiovascular disease risk score, Duke coronary artery disease score, and a logistic regression statistical model. 224 patients (21%) were identified as RPP. Feature selection in ML identifies that quantitative computed tomography variables were higher-ranking features, followed by qualitative computed tomography variables and clinical/laboratory variables. ML model 3 exhibited the highest discriminatory performance to identify individuals who would experience RPP when compared with atherosclerotic cardiovascular disease risk score, the other ML models, and the statistical model (area under the receiver operating characteristic curve in ML model 3, 0.83 [95% CI 0.78-0.89], versus atherosclerotic cardiovascular disease risk score, 0.60 [0.52-0.67]; Duke coronary artery disease score, 0.74 [0.68-0.79]; ML model 1, 0.62 [0.55-0.69]; ML model 2, 0.73 [0.67-0.80]; all P&lt;0.001; statistical model, 0.81 [0.75-0.87], P=0.128). Conclusions Based on a ML framework, quantitative atherosclerosis characterization has been shown to be the most important feature when compared with clinical, laboratory, and qualitative measures in identifying patients at risk of RPP

Macrophage Depletion in Hypertensive Rats Accelerates Development of Cardiomyopathy

Inflammation contributes to the process of ventricular remodeling after acute myocardial injury. To investigate the role of macrophages in the chronic process of cardiac remodeling, they were selectively depleted by intravenous administration of liposomal clodronate in heart failure-prone hypertensive Ren-2 rats from the age of 7 until 13 weeks. plain liposomes were used for comparison. Liposomal clodronate treatment reduced the number of blood monocytes and decreased the number of macrophages in the myocardium. Compared to plain liposomes, liposomal clodronate treatment rapidly worsened left ventricular ejection function in hypertensive rats. Liposomal clodronate-treated Ren-2 rat hearts showed areas of myocyte loss with abundant inflammatory cell infiltration, predominantly comprising CD4 positive T lymphocytes. The current-study showed that lack of macrophages vas associated with earlier development of myocardial dysfunction in hypertensive rats. Modulation of macrophage function may be of value in the evolution of cardiomyopath