Abstract Background Statins can regress coronary atheroma and lower clinical events. Although pre-clinical studies suggest procalcific effects of statins in vitro, it remains unclear if statins can ...modulate coronary atheroma calcification in vivo. Objectives This study compared changes in coronary atheroma volume and calcium indices (CaI) in patients receiving high-intensity statin therapy (HIST), low-intensity statin therapy (LIST), and no-statin therapy. Methods In a post-hoc patient-level analysis of 8 prospective randomized trials using serial coronary intravascular ultrasound, serial changes in coronary percent atheroma volume (PAV) and CaI were measured across matched coronary segments in patients with coronary artery disease. Results Following propensity-weighted adjustment for differences in baseline and changes in clinical, laboratory, and ultrasonic characteristics, HIST (n = 1,545) associated with PAV regression from baseline (−0.6 ± 0.1%; p < 0.001), whereas both LIST (n = 1,726) and no-statin therapy (n = 224) associated with PAV progression (+0.8 ± 0.1% and +1.0 ± 0.1%; p < 0.001, respectively; p < 0.001 for both HIST vs. LIST and HIST vs. no-statin; p = 0.35 for LIST vs. no-statin). Significant increases in CaI from baseline were noted across all groups (median interquartile range HIST, +0.044 0.0–0.12; LIST, +0.038 0.0–0.11; no-statin, +0.020 0.0–0.10; p < 0.001 for all), which could relate to statin intensity (p = 0.03 for LIST vs. no-statin; p = 0.007 for HIST vs. no-statin; p = 0.18 for HIST vs. LIST). No correlations were found between changes in CaI and on-treatment levels of atherogenic and antiatherogenic lipoproteins, and C-reactive protein, in either of the HIST groups or the no-statin group. Conclusions Independent of their plaque-regressive effects, statins promote coronary atheroma calcification. These findings provide insight as to how statins may stabilize plaque beyond their effects on plaque regression.
Bioprosthetic Valve Thrombosis Puri, Rishi, MBBS, PhD; Auffret, Vincent, MD, MSc; Rodés-Cabau, Josep, MD
Journal of the American College of Cardiology,
05/2017, Letnik:
69, Številka:
17
Journal Article
Recenzirano
Odprti dostop
Abstract Bioprosthetic valve (BPV) thrombosis is considered a relatively rare clinical entity. Yet a more recent analysis involving a more systematic echocardiographic follow-up, the advent of ...transcatheter heart valve (THV) technologies coupled with the highly sensitive nature of 4-dimensional computed tomographic imaging for detecting subclinical thrombi upon both surgically implanted and THVs, has generated enormous interest in this field, casting new light on both its true incidence and clinical relevance. Debate continues among clinicians as to both the clinical relevance of subclinical BPV thrombosis and the value of empirical oral anticoagulation following BPV implantation. Furthermore, currently no systematic, prospective data exist regarding the optimal treatment approach in THV recipients. The authors provide an overview of the clinical and subclinical spectrum of BPV thrombosis of surgical and THVs, outline its diagnostic challenges, summarize its pathophysiological basis, and discuss various therapeutic options that are emerging, particularly within the rapidly expanding field of THV implantation.
Abstract Tricuspid valve (TV) disease has been relatively neglected, despite the known association between severe tricuspid regurgitation (TR) and mortality. Few patients undergo isolated tricuspid ...surgery, which remains associated with high in-hospital mortality rates, particularly in patients with prior left-sided valve surgery. Patients with severe TR are often managed medically for years before TV repair or replacement. Current guidelines recommend TV repair in the presence of a dilated tricuspid annulus at the time of a left-sided valve surgical intervention, even if regurgitation is mild. This proposed algorithm aims to prevent the inevitable progression to severe TR and the need for a second surgical intervention. Recently, novel transcatheter treatment options were developed for treating patients with severe TR and right heart failure with prohibitive surgical risk. Here we describe currently available transcatheter treatment options for severe TR implanted at different levels: the junction between vena cavae and right atrium; the tricuspid annulus; or between TV leaflets, improving coaptation.
Abstract
Aims
Emerging evidence suggests that remnant cholesterol (RC) promotes atherosclerotic cardiovascular disease (ASCVD). We aimed to estimate RC-related risk beyond low-density lipoprotein ...cholesterol (LDL-C) and apolipoprotein B (apoB) in patients without known ASCVD.
Methods and results
We pooled data from 17 532 ASCVD-free individuals from the Atherosclerosis Risk in Communities study (n = 9748), the Multi-Ethnic Study of Atherosclerosis (n = 3049), and the Coronary Artery Risk Development in Young Adults (n = 4735). RC was calculated as non-high-density lipoprotein cholesterol (non-HDL-C) minus calculated LDL-C. Adjusted Cox models were used to estimate the risk for incident ASCVD associated with log RC levels. We also performed discordance analyses examining relative ASCVD risk in RC vs. LDL-C discordant/concordant groups using difference in percentile units (>10 units) and clinically relevant LDL-C targets. The mean age of participants was 52.3 ± 17.9 years, 56.7% were women and 34% black. There were 2143 ASCVD events over the median follow-up of 18.7 years. After multivariable adjustment including LDL-C and apoB, log RC was associated with higher ASCVD risk hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.45–1.89. Moreover, the discordant high RC/low LDL-C group, but not the low RC/high LDL-C group, was associated with increased ASCVD risk compared to the concordant group (HR 1.21, 95% CI 1.08–1.34). Similar results were shown when examining discordance across clinical cutpoints.
Conclusions
In ASCVD-free individuals, elevated RC levels were associated with ASCVD independent of traditional risk factors, LDL-C, and apoB levels. The mechanisms of RC association with ASCVD, surprisingly beyond apoB, and the potential value of targeted RC-lowering in primary prevention need to be further investigated.
Graphical Abstract
The purpose of this study was to determine the effect of evolocumab on optical coherence tomography (OCT) measures of plaque composition.
The proprotein convertase subtilisin kexin type-9 inhibitor ...evolocumab produced coronary atheroma regression in statin-treated patients.
Patients with a non–ST-segment elevation myocardial infarction were treated with monthly evolocumab 420 mg (n = 80) or placebo (n = 81) for 52 weeks. Patients underwent serial OCT and intravascular ultrasound imaging within a matched arterial segment of a nonculprit vessel. The primary analysis determined the change in the minimum fibrous cap thickness and maximum lipid arc throughout the imaged arterial segment. Additional analyses determined changes in OCT features in lipid-rich plaque regions and plaque burden. Safety and tolerability were evaluated.
Among treated patients, (age 60.5 ± 9.6 years; 28.6% women; low-density lipoprotein cholesterol LDL-C, 141.3 ± 33.1 mg/dL), 135 had evaluable imaging at follow-up. The evolocumab group achieved lower LDL-C levels (28.1 vs 87.2 mg/dL; P < 0.001). The evolocumab group demonstrated a greater increase in minimum fibrous cap thickness (+42.7 vs +21.5 μm; P = 0.015) and decrease in maximum lipid arc (−57.5o vs. −31.4o; P = 0.04) and macrophage index (−3.17 vs −1.45 mm; P = 0.04) throughout the arterial segment. Similar benefits of evolocumab were observed in lipid-rich plaque regions. Greater regression of percent atheroma volume was observed with evolocumab compared with placebo (−2.29% ± 0.47% vs −0.61% ± 0.46%; P = 0.009). The groups did not differ regarding changes in microchannels or calcium.
The combination of statin and evolocumab after a non–ST-segment elevation myocardial infarction produces favorable changes in coronary atherosclerosis consistent with stabilization and regression. This demonstrates a potential mechanism for the improved clinical outcomes observed achieving very low LDL-C levels following an acute coronary syndrome. (Imaging of Coronary Plaques in Participants Treated With Evolocumab; NCT03570697)
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Abstract Bioprosthetic valve use has increased significantly. Considering their limited durability, there will remain an ongoing clinical need for repairing or replacing these prostheses in the ...future. The current standard of care for treating bioprosthetic valve degeneration involves redo open-heart surgery. However, repeat cardiac surgery may be associated with significant morbidity and mortality. With the rapid evolution of transcatheter heart valve therapies, the feasibility and safety of implanting a transcatheter heart valve within a failed tissue valve has been established. We review the historical perspective of transcatheter valve-in-valve therapy, as well as the main procedural challenges and clinical outcomes associated with this new less invasive treatment option.
Humans and nonhuman primates are vulnerable to age- and menopause-related decline in working memory, a cognitive function reliant on the energy-demanding recurrent excitation of neurons within ...Brodmann’s Area 46 of the dorsolateral prefrontal cortex (dlPFC). Here, we tested the hypothesis that the number and morphology (straight, curved, or donut-shaped) of mitochondria in dlPFC presynaptic boutons are altered with aging and menopause in rhesus monkeys (Macaca mulatta) and that these metrics correlate with delayed response (DR) accuracy, a well-characterized measure of dlPFC-dependent working memory. Although presynaptic bouton density or size was not significantly different across groups distinguished by age or menses status, DR accuracy correlated positively with the number of total and straight mitochondria per dlPFC bouton. In contrast, DR accuracy correlated inversely with the frequency of boutons containing donut-shaped mitochondria, which exhibited smaller active zone areas and fewer docked synaptic vesicles than those with straight or curved mitochondria. We then examined the effects of estrogen administration to test whether a treatment known to improve working memory influences mitochondrial morphology. Aged ovariectomized monkeys treated with vehicle displayed significant working memory impairment and a concomitant 44% increase in presynaptic donut-shaped mitochondria, both of which were reversed with cyclic estradiol treatment. Together, our data suggest that hormone replacement therapy may benefit cognitive aging, in part by promoting mitochondrial and synaptic health in the dlPFC.
Accumulating clinical experience and technological improvements have provided the basis for transcatheter aortic valve implantation (TAVI) to emerge as a well-established means for treating patients ...with severe symptomatic aortic stenosis at high or prohibitive surgical risk. During this decade, TAVI has emerged as a valid alternative to surgical aortic valve replacement in patients at intermediate surgical risk, and several studies are currently being performed to evaluate the role of TAVI in patients at low surgical risk. Furthermore, promising, but preliminary, data are emerging on the efficacy of TAVI for treating patients with bicuspid aortic valve disease, as well as patients with pure aortic regurgitation. In this Perspectives article, we summarize the evolving indications for TAVI, and give our opinion on the future perspectives for this procedure.
Abstract Background Identifying transcatheter aortic valve replacement (TAVR) patients at high risk for cerebrovascular events (CVE) is of major clinical relevance. However, predictors have varied ...across studies. Objectives The purpose of this study was to analyze the predictors of 30-day CVE post-TAVR. Methods A systematic review of studies that reported the incidence of CVE post-TAVR while providing raw data for predictors of interest was performed. Data on study, patient, and procedural characteristics were extracted. Crude risk ratios (RRs) and 95% confidence intervals for each predictor were calculated. Results Sixty-four studies involving 72,318 patients (2,385 patients with a CVE within 30 days post-TAVR) were analyzed. Incidence of CVE ranged from 1% to 11% (median 4%) without significant differences between single and multicenter studies, or according to CVE adjudication availability. The summary RRs indicated lower risk for men (RR: 0.82; p = 0.02) and higher risk for patients with chronic kidney disease (RR: 1.29; p = 0.03) and with new-onset atrial fibrillation post-TAVR (RR: 1.85; p = 0.005), and for procedures performed within the first half of center experience (RR: 1.55; p = 0.003). The use of balloon post-dilation tended to be associated with a higher risk of CVE (RR: 1.43; p = 0.07). Valve type (balloon-expandable vs. self-expandable, p = 0.26) and approach (transfemoral vs. nontransfemoral, p = 0.81) did not predict CVE. Conclusions Female sex, chronic kidney disease, enrollment date, and new-onset atrial fibrillation were predictors of CVE post-TAVR. This study provides effect estimates to identify high-risk TAVR patients for early CVE, providing possible guidance for tailored preventive strategies.
Incremental low-density lipoprotein (LDL) cholesterol lowering with the proprotein convertase subtilisin kexin type 9 inhibitor evolocumab regresses coronary atherosclerosis in statin-treated ...patients.
The purpose of this study was to evaluate the effect of adding evolocumab to statin therapy on coronary plaque composition.
A total of 968 statin-treated coronary artery disease patients underwent serial coronary intravascular ultrasound imaging at baseline and following 76 weeks of treatment with placebo or evolocumab 420 mg monthly. Plaque composition changes were determined in 331 patients with evaluable radiofrequency analysis of the ultrasound backscatter signal.
Compared with statin monotherapy, evolocumab further reduced LDL cholesterol (33.5 mg/dl vs. 89.9 mg/dl; p < 0.0001) and induced regression of percent atheroma volume (−1.2% vs. +0.17%; p < 0.0001) and total atheroma volume (−3.6 mm3 vs. −0.8 mm3; p = 0.04). No difference was observed between the evolocumab and placebo groups in changes in calcium (1.0 ± 0.3 mm3 vs. 0.6 ± 0.3 mm3; p = 0.49), fibrous (−3.0 ± 0.6 mm3 vs. −2.4 ± 0.6 mm3; p = 0.49), fibrofatty (−5.0 ± 1.0 mm3 vs. −3.0 ± 1.0 mm3; p = 0.49), and necrotic (−0.6 ± 0.5 mm3 vs. −0.1 ± 0.5 mm3; p = 0.49) volumes. An inverse correlation was observed between changes in LDL cholesterol and plaque calcification (r = −0.15; p < 0.001).
The addition of evolocumab to a statin did not produce differential changes in plaque composition compared with statin monotherapy. This suggests that evaluation of plaque morphology using virtual histology imaging may provide no incremental information about the plaque effects of evolocumab beyond measurement of plaque burden. (GLobal Assessment of Plaque reGression With a PCSK9 antibOdy as Measured by intraVascular Ultrasound GLAGOV; NCT01813422)
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