Abstract Objectives The purpose of this study was to explore the diagnostic usefulness of hybrid cardiac magnetic resonance (CMR) and positron emission tomography (PET) using 18F-fluorodeoxyglucose ...(FDG) for active cardiac sarcoidosis. Background Active cardiac sarcoidosis (aCS) is underdiagnosed and has a high mortality. Methods Patients with clinical suspicion of aCS underwent hybrid CMR/PET with late gadolinium enhancement (LGE) and FDG to assess the pattern of injury and disease activity, respectively. Patients were categorized visually as magnetic resonance (MR)+PET+ (characteristic LGE aligning exactly with increased FDG uptake), MR+PET− (characteristic LGE but no increased FDG), MR−PET− (neither characteristic LGE nor increased FDG), and MR−PET+ (increased FDG uptake in absence of characteristic LGE) and further characterized as aCS+ (MR+PET+) or aCS− (MR+PET−, MR−PET−, MR−PET+). FDG uptake was quantified using maximum target-to-normal-myocardium ratio and the net uptake rate ( K i ) from dynamic Patlak analysis. Receiver operating characteristic methods were used to identify imaging biomarkers for aCS. FDG PET was assessed using computed tomography/PET in 19 control subjects with healthy myocardium. Results A total of 25 patients (12 males; 54.9 ± 9.8 years of age) were recruited prospectively; 8 were MR+PET+, suggestive of aCS; 1 was MR+PET−, consistent with inactive cardiac sarcoidosis; and 8 were MR−PET−, with no imaging evidence of cardiac sarcoidosis. Eight patients were MR−PET+ (6 with global myocardial FDG uptake, 2 with focal-on-diffuse uptake); they demonstrated distinct K i values and hyperintense maximum standardized uptake value compared with MR+PET+ patients. Similar hyperintense patterns of global (n = 9) and focal-on-diffuse (n = 2) FDG uptake were also observed in control patients, suggesting physiological myocardial uptake. Maximum target-to-normal-myocardium ratio values were higher in the aCS+ group (p < 0.001), demonstrating an area under the curve of 0.98 on receiver operating characteristic analysis for the detection of aCS, with an optimal maximum target-to-normal myocardium ratio threshold of 1.2 (Youden index: 0.94). Conclusions CMR/PET imaging holds major promise for the diagnosis of aCS, providing incremental information about both the pattern of injury and disease activity in a single scan. (In Vivo Molecular Imaging MRI of Atherothrombotic Lesions; NCT01418313 )
Abstract Background Cardiac fibrosis (CF) is associated with increased ventricular stiffness and diastolic dysfunction and is an independent predictor of long-term clinical outcomes of patients with ...heart failure (HF). We previously showed that the matricellular CCN5 protein is cardioprotective via its ability to inhibit CF and preserve cardiac contractility. Objectives This study examined the role of CCN5 in human heart failure and tested whether CCN5 can reverse established CF in an experimental model of HF induced by pressure overload. Methods Human hearts were obtained from patients with end-stage heart failure. Extensive CF was induced by applying transverse aortic constriction for 8 weeks, which was followed by adeno-associated virus-mediated transfer of CCN5 to the heart. Eight weeks following gene transfer, cellular and molecular effects were examined. Results Expression of CCN5 was significantly decreased in failing hearts from patients with end-stage heart failure compared to nonfailing hearts. Trichrome staining and myofibroblast content measurements revealed that the established CF had been reversed by CCN5 gene transfer. Anti-CF effects of CCN5 were associated with inhibition of the transforming growth factor beta signaling pathway. CCN5 significantly inhibited endothelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation, which are 2 critical processes for CF progression, both in vivo and in vitro. In addition, CCN5 induced apoptosis in myofibroblasts, but not in cardiomyocytes or fibroblasts, both in vivo and in vitro. CCN5 provoked the intrinsic apoptotic pathway specifically in myofibroblasts, which may have been due the ability of CCN5 to inhibit the activity of NFκB, an antiapoptotic molecule. Conclusions CCN5 can reverse established CF by inhibiting the generation of and enhancing apoptosis of myofibroblasts in the myocardium. CCN5 may provide a novel platform for the development of targeted anti-CF therapies.
Abstract Objectives The aim of this study is to compare the relative merits of optical coherence tomography (OCT), intravascular ultrasound (IVUS), and near infrared spectroscopy (NIRS) in patients ...with coronary artery disease for the prediction of periprocedural myocardial infarction (MI). Background Although several individual intravascular imaging modalities have been employed to predict periprocedural MI, it is unclear which of the imaging tools would best allow prediction of this complication. Methods We retrospectively analyzed 110 patients who underwent OCT, IVUS, and NIRS. Periprocedural MI was defined as a post-procedural cardiac troponin I (cTnI) elevation above 3× the upper limit of normal; analysis was also performed for cTnI ≥5× the upper limit of normal. Results cTnI ≥3× was observed in 10 patients (9%) and 8 patients had cTnI ≥5×. By OCT, minimum cap thickness was significantly lower (55 vs. 90 μm, p < 0.01), and the plaque burden by IVUS (84 ± 9% vs. 77 ± 8%, p < 0.01) and maximum 4-mm lipid core burden index by NIRS (556 vs. 339, p < 0.01) were greater in the cTnI ≥3× group. Multivariate logistic regression analysis identified cap thickness as the only independent predictor for cTnI ≥3× the upper limit of normal (odds ratio OR: 0.90, p = 0.02) or cTnI ≥5× (OR: 0.91, p = 0.04). If OCT findings were excluded from the analysis, plaque burden (OR: 1.13, p = 0.045) and maximum 4-mm lipid core burden index (OR: 1.003, p = 0.037) emerged to be the independent predictors. Conclusions OCT-based fibrous cap thickness is the most important predictor of periprocedural MI. In the absence of information about cap thickness, NIRS lipid core or IVUS plaque burden best determined the likelihood of the periprocedural event.
Family-Based Approaches to Cardiovascular Health Promotion Vedanthan, Rajesh, MD, MPH; Bansilal, Sameer, MD, MS; Soto, Ana Victoria, MD ...
Journal of the American College of Cardiology,
04/2016, Letnik:
67, Številka:
14
Journal Article
Recenzirano
Odprti dostop
Abstract Cardiovascular disease is the leading cause of mortality in the world, and the increasing burden is largely a consequence of modifiable behavioral risk factors that interact with genomics ...and the environment. Continuous cardiovascular health promotion and disease prevention throughout the lifespan is critical, and the family is a central entity in this process. In this review, we describe the potential rationale and mechanisms that contribute to the importance of family for cardiovascular health promotion, focusing on: 1) mutual interdependence of the family system; 2) shared environment; 3) parenting style; 4) caregiver perceptions; and 5) genomics. We conclude that family-based approaches that target both caregivers and children, encourage communication among the family unit, and address the structural and environmental conditions in which families live and operate are likely to be the most effective approach to promote cardiovascular health. We describe lessons learned, future implications, and applications to ongoing and planned studies.
Abstract Background Despite the extensive evidence for the beneficial effects of statins on clinical outcomes, the mechanisms underlying these effects in remain elusive. Objectives To assess the ...changes in plaque morphology by intravascular imaging with a comprehensive evaluation of cholesterol efflux capacity (CEC) and peripheral blood mononuclear cells (PBMC) transcriptomics in patients receiving high-dose statin therapy. Methods In a prospective study, 85 patients with stable multivessel coronary artery disease underwent percutaneous coronary intervention for a culprit lesion followed by intracoronary multi-modality imaging including optical coherence tomography (OCT) of an obstructive non-culprit lesion (NCL). All subjects received 40 mg of rosuvastatin every day for 8-12 weeks, when the NCL was reimaged and intervention was performed. Blood samples were drawn at both times to assess cholesterol CEC and transcriptomic profile in PBMC. Results Baseline OCT minimal fibrous cap thickness (FCT) was 100.9 ± 41.7 μm and CEC 0.81 ± 0.14, which increased upon follow-up-FCT (108.6 ± 39.6 μm, P<0.001), CEC (0.84 ± 0.14, P=0.003). The prevalence of thin-cap fibroatheroma reduced from 20.0% to 7.1% (P=0.003). The changes in FCT were independently associated with the increase in CEC by multivariate analysis (β, 0.30; 95%CI, 0.07-0.54; P=0.01). Microarray analysis of PBMC detected 117 differentially expressed genes at follow-up compared to baseline including genes playing key role in cholesterol synthesis ( SQLE ), regulation of fatty acids unsaturation ( FADS1 ), cellular cholesterol uptake ( LDLR ), efflux ( ABCA1 , ABCG1 ) and inflammation ( DHCR24 ). Weighted coexpression network analysis revealed unique clusters of genes associated with favorable changes in FCT and CEC. Conclusions The study demonstrates an independent association between the thickening of the fibrous cap and improved CEC that may contribute to morphological changes suggesting plaque stabilization among patients on intensive statin therapy. Furthermore, the significant transcriptomic perturbations related to cholesterol synthesis, regulation of fatty acid unsaturation, cellular cholesterol uptake, efflux and inflammation may co-operate in determining the beneficial effects of statin on plaque stabilization.
Summary The traditional paradigm of cardiovascular disease research derives insight from large-scale, broadly inclusive clinical studies of well-characterized pathologies. These insights are then put ...into practice according to standardized clinical guidelines. However, stagnation in the development of new cardiovascular therapies and variability in therapeutic response implies that this paradigm is insufficient for reducing the cardiovascular disease burden. In this state-of-the-art review, we examine 3 interconnected ideas we put forth as key concepts for enabling a transition to precision cardiology: 1) precision characterization of cardiovascular disease with machine learning methods; 2) the application of network models of disease to embrace disease complexity; and 3) using insights from the previous 2 ideas to enable pharmacology and polypharmacology systems for more precise drug-to-patient matching and patient-disease stratification. We conclude by exploring the challenges of applying a precision approach to cardiology, which arise from a deficit of the required resources and infrastructure, and emerging evidence for the clinical effectiveness of this nascent approach.
Atherosclerosis research has classically followed 2 intertwining lines of investigation concerning atherosclerosis as a local process (the “high-risk plaque”) and as a systemic disease (the ...“high-risk patient”). Over time, the weight of attention has swung, like a pendulum, between these 2 related foci. With optimal medical therapy and attention to risk factors firmly established as fundamental aspects of management, in the past year, we have nevertheless perceived a shift in the pendulum toward renewed focus on the local plaque. We contend that this shift results from a convergence of major advances in understanding the biology of plaque progression, novel sophisticated invasive and noninvasive imaging modalities for the in vivo characterization of plaque composition and inflammation, and emerging data and technologies that have renewed interest in locally targeted interventions. Here, we review the dynamic and exciting progress that has occurred over the last 12 months in this arena, while acknowledging future work that remains to be done to refine and validate new imaging modalities and therapies.
Objectives This study sought to determine the impact of short-term intensive statin therapy on intracoronary plaque lipid content. Background Statin therapy significantly reduces the risk for ...thrombotic events. Whether or not these benefits are attributable to reduction in plaque lipid content remains to be properly documented in human obstructive coronary artery disease (CAD). Methods We randomized 87 patients with multivessel CAD undergoing percutaneous coronary intervention and at least 1 other severely obstructive (fractional flow reserve FFR ≤0.8) nontarget lesion (NTL) to intensive (rosuvastatin 40 mg daily) or standard-of-care lipid-lowering therapy. NTLs were evaluated at baseline and after 7 weeks of therapy with FFR, near-infrared spectroscopy, and intravascular ultrasound. The primary endpoint was the change in lipid-core burden index at the 4-mm maximal segment (LCBI4mm max), wherever this occurred within the lesion. Results Upon follow-up, median reduction (95% confidence interval) in LCBI4mm max was significantly greater in the intensive versus standard group (−149.1 −210.9 to −42.9 vs. 2.4 −36.1 to 44.7; p = 0.01). Results remained consistent after adjustment for baseline differences in LCBI between groups and use of change in LCBI across the entire lesion as the dependent outcome. Conclusions Short-term intensive statin therapy may reduce lipid content in obstructive lesions. These hypothesis-generating findings warrant confirmation in larger studies with longer follow-up. (Reduction in YEllow Plaque by Aggressive Lipid LOWering Therapy YELLOW); NCT01567826 )
Coronary Artery Manifestations of Fibromuscular Dysplasia Michelis, Katherine C., MD; Olin, Jeffrey W., DO; Kadian-Dodov, Daniella, MD ...
Journal of the American College of Cardiology,
09/2014, Letnik:
64, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Abstract Fibromuscular dysplasia (FMD) involving the coronary arteries is an uncommon but important condition that can present as acute coronary syndrome, left ventricular dysfunction, or potentially ...sudden cardiac death. Although the classic angiographic “string of beads” that may be observed in renal artery FMD does not occur in coronary arteries, potential manifestations include spontaneous coronary artery dissection, distal tapering or long, smooth narrowing that may represent dissection, intramural hematoma, spasm, or tortuosity. Importantly, FMD must be identified in at least one other noncoronary arterial territory to attribute any coronary findings to FMD. Although there is limited evidence to guide treatment, many lesions heal spontaneously; thus, a conservative approach is generally preferred. The etiology is poorly understood, but there are ongoing efforts to better characterize FMD and define its genetic and molecular basis. This report reviews the clinical course of FMD involving the coronary arteries and provides guidance for diagnosis and treatment strategies.
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