Antiplatelet Therapy in End-stage Renal Disease Patients on Maintenance Dialysis: a State-of-the-art Review.

Patients with end-stage renal disease (ESRD) on maintenance dialysis have an increased risk of ischaemic events, such as recurrent myocardial infarction (MI) and stroke. Potent antiplatelet therapy may help mitigate this risk. Nonetheless, ERSD patients are also at increased risk of bleeding due to their complex vascular milieu, which limits the routine use of potent P2Y12 inhibitors. Moreover, these patients are often underrepresented or excluded from major clinical trials leaving a significant gap in existing knowledge. Understanding the mechanisms of this paradox may serve as a benchmark for the development of ESRD trials. The present review aims to provide an overview of the pathophysiological nature of increased bleeding and ischaemic risks in ERSD patients as well as summarize available evidence of antiplatelet use and propose new concepts to guide physicians in selecting appropriate drug regimes for this high-risk cohort.

Hyperglycemia Induces Trained Immunity in Macrophages and Their Precursors and Promotes Atherosclerosis.

BACKGROUND: Cardiovascular risk in diabetes remains elevated despite glucose-lowering therapies. We hypothesized that hyperglycemia induces trained immunity in macrophages, promoting persistent proatherogenic characteristics. METHODS: Bone marrow-derived macrophages from control mice and mice with diabetes were grown in physiological glucose (5 mmol/L) and subjected to RNA sequencing (n=6), assay for transposase accessible chromatin sequencing (n=6), and chromatin immunoprecipitation sequencing (n=6) for determination of hyperglycemia-induced trained immunity. Bone marrow transplantation from mice with (n=9) or without (n=6) diabetes into (normoglycemic) Ldlr-/- mice was used to assess its functional significance in vivo. Evidence of hyperglycemia-induced trained immunity was sought in human peripheral blood mononuclear cells from patients with diabetes (n=8) compared with control subjects (n=16) and in human atherosclerotic plaque macrophages excised by laser capture microdissection. RESULTS: In macrophages, high extracellular glucose promoted proinflammatory gene expression and proatherogenic functional characteristics through glycolysis-dependent mechanisms. Bone marrow-derived macrophages from diabetic mice retained these characteristics, even when cultured in physiological glucose, indicating hyperglycemia-induced trained immunity. Bone marrow transplantation from diabetic mice into (normoglycemic) Ldlr-/- mice increased aortic root atherosclerosis, confirming a disease-relevant and persistent form of trained innate immunity. Integrated assay for transposase accessible chromatin, chromatin immunoprecipitation, and RNA sequencing analyses of hematopoietic stem cells and bone marrow-derived macrophages revealed a proinflammatory priming effect in diabetes. The pattern of open chromatin implicated transcription factor Runt-related transcription factor 1 (Runx1). Similarly, transcriptomes of atherosclerotic plaque macrophages and peripheral leukocytes in patients with type 2 diabetes were enriched for Runx1 targets, consistent with a potential role in human disease. Pharmacological inhibition of Runx1 in vitro inhibited the trained phenotype. CONCLUSIONS: Hyperglycemia-induced trained immunity may explain why targeting elevated glucose is ineffective in reducing macrovascular risk in diabetes and suggests new targets for disease prevention and therapy.

Coronary revascularization in patients with left ventricle systolic dysfunction, current challenges and clinical outcomes.

The effects of coronary revascularization in patients with left ventricle systolic dysfunction (LVSD) are not well studied. The decision about revascularization and its timing remain challenging, not only related to procedural risk, but also linked to other several limitations including assessment of ischemia, viability, and ability to predict LV recovery. The role of viability as a prognostic marker for patients with LVSD and its use as a therapeutic target remains debatable. In this article, we will review the role of LVSD in patients undergoing coronary revascularization alongside the role of ischemia and viability assessment. We will provide a review of the literature on the outcomes of coronary revascularization, both surgically and percutaneously, in patients with LVSD.

Mechanical circulatory support in acute myocardial infarction complicated by cardiogenic shock.

Patients with acute myocardial infarction (MI) complicated by cardiogenic shock (CS) have poor prognosis. Over the last two decades, there has been some improvement in mortality rates associated with CS. Initial measures to stabilise patients should follow a shock protocol, including therapies such as volume expansion, inotropes/vasopressors, and early coronary revascularisation. The use of mechanical circulatory support (MCS) devices demonstrated better haemodynamic and metabolic profiles for patients with CS. However, these benefits have not been consistently translated into significant reductions in cardiovascular adverse events. This review aims to discuss emerging concepts related to CS including an update on its classification and pathophysiology. The focus is on recent evidence regarding the use of MCS and the timing of initiating in patients with CS.

Clinical outcomes of percutaneous coronary intervention in high-risk patients turned down for surgical revascularization.

AIMS: There are limited data on outcomes of PCI in surgical turndown patientsespecially in those presenting with ACS. METHODS AND RESULTS: A retrospective analysis of prospectively collected data of patients who were turned down for CABG and had PCI between 2013 and 2020. All consecutive patients (449), ACS (n = 245) and no-ACS (n = 204) were included. In-hospital complications occurred in 28 patients (6.2%). At 30 days, 27 patients (6.0%) died (18 patients in the ACS group [7.3%] vs. 9 patients in the no-ACS group [4.4%], p = 0.23). Following multivariate analysis, no significant difference in long-term mortality was observed between the two groups (median follow-up of 4 [2-6] years, hazard ratio [HR]: 1.08, 95% confidence interval [CI]: 0.75-1.58, p = 0.667). In propensity score-matched analysis, the adjusted mortality risk was also not different between the groups (HR: 0.74, 95% CI: 0.25-1.26, p = 0.374). Independent predictors of mortality included chronic kidney disease stage ≥ 3 (HR: 1.64, 95% CI: 1.13-2.39, p = 0.009), high European System for Cardiac Operative Risk Evaluation II (HR: 1.02, 95% CI: 1.00-1.05, p = 0.035), and laser atherectomy use (HR: 3.35, 95% CI: 1.32-8.54, p = 0.011). CONCLUSIONS: PCI in surgical patients turndown patients appears safe. ACSpresentation was associated with more comorbid illnesses; however, afteradjustment, ACS did not independently confer additional risk of mortality.

Aspirin Versus Dual Antiplatelet Therapy in Patients Undergoing Trans-Catheter Aortic Valve Implantation, Updated Meta-Analysis.

BACKGROUND: The Antiplatelet Therapy for Patients Undergoing Transcatheter Aortic-Valve Implantation (POPular TAVI) trial reported comparable composite endpoints of ischemic events using aspirin compared to dual antiplatelet therapy (DAPT). However, this trial was not powered to detect individual differences in ischemic events. We sought to conduct a meta-analysis to compare aspirin to DAPT on ischemic and bleeding events following TAVI. METHODS: The MEDLINE database was searched from inception until September 2020 and only randomized clinical trials of patients receiving antiplatelet therapy following TAVI were included. The treatment effect was reported as rate ratios (RRs) with 95% confidence intervals. RESULTS: Four randomized clinical trials of 1086 TAVI patients were included. There was a 51% reduction in major or life-threatening bleeding with aspirin compared with DAPT [RR 0.49, (95%CI 0.31 to 0.78)]. Aspirin was not associated with an increased risk of death [RR 1.01, (95%CI 0.62 to 1.65)], cardiovascular death [RR 1.15, (95%CI 0.56 to 2.36)], ischemic stroke [RR 0.93, (95%CI 0.51 to 1.70)], or MI [RR 0.53, (95%CI 0.18 to 1.57)]. CONCLUSIONS: This meta-analysis supports the use of aspirin as the optimal antiplatelet strategy following TAVI procedures in reducing bleeding without an increase in ischemic events compared with dual antiplatelet therapy.

Current and novel echocardiographic assessment of left ventricular systolic function in aortic stenosis-A comprehensive review.

Aortic stenosis (AS) is a complex and progressive condition that can significantly reduce the quality of life and increase the incidence of premature mortality. Transthoracic echocardiography (TTE) is the gold standard imaging modality for the assessment of AS severity. While left ventricular ejection fraction (LVEF) derived from TTE is a very well-understood parameter, limitations such as high inter and intra-observer variability, insensitivity to sub-clinical dysfunction, and influence of loading conditions make LVEF a complicated and unreliable parameter. Myocardial deformation imaging has been identified as a promising parameter for identifying subclinical left ventricular dysfunction, however, this parameter is still afterload dependent. Myocardial Work is a promising novel assessment technique that accounts for afterload by combining the use of myocardial deformation imaging and non-invasive blood pressure to provide a more comprehensive assessment of mechanics beyond LVEF. This review evaluates the evidence for various echocardiographic assessment parameters used to quantify left ventricular function including myocardial work in patients with AS.

Antiplatelet Therapy in Patients Undergoing Elective Percutaneous Coronary Intervention.

PURPOSE OF REVIEW: The evidence for use of dual antiplatelet therapy (DAPT) for patients undergoing percutaneous coronary intervention (PCI) in the elective setting is relatively sparse and is based on data from more than two decades ago. We will review the evidence supporting the use of DAPT with focus on stable patients undergoing elective PCI, including the role of potent P2Y12 inhibitors, modified DAPT durations, and more recently, aspirin discontinuation. RECENT FINDINGS: Clopidogrel is the recommended P2Y12 inhibitor in the elective PCI setting. The benefit of more potent P2Y12 inhibitors such as ticagrelor or prasugrel in stable patients is unproven, but their use might be reasonable in those with high clinical or angiographic features of increased ischemic risk without increased risk of bleeding. Moreover, extending DAPT beyond 12 months is associated with a reduction in ischemic events but also increased bleeding. In contrast, shortening DAPT (3-6 months) reduces bleeding compared with 1 year of treatment, but it is also probably associated with increased ischemic events, mainly in higher-risk patients undergoing complex PCI. Recently, early aspirin discontinuation at 3 months (and perhaps as early as 1 month) following PCI reduces bleeding, with no evidence to suggest an increase in ischemic events. Clopidogrel is the P2Y12 inhibitor of choice, while more data are required to support the use of more potent P2Y12 inhibitors in stable patients. The duration of DAPT should be tailored to individual patient ischemic and bleeding risks. New strategies, such as early aspirin discontinuation, are promising to reduce bleeding risk without increase in ischemic risk.

Sex-based difference in fractional flow reserve and its impact on clinical outcomes.

BACKGROUND: Obesity is a real public health problem and is of growing concern. People are resorting to surgical or endoscopic means to fight against overweight and obesity. In recent years, there has been a marked increase in the use of these means and in particular the insertion of a gastric balloon which seems to present less risk than surgical methods. Renal complications from intragastric balloon placement are extremely rare. We report here the case of compression of the left renal vein revealed by lumbar pain and hematuria in an overweight 39-year-old woman who benefited from the balloon gastric placement one month before symptoms. The scanner made the diagnosis and showed a good evolution after the withdrawal of the balloon. METHODS: This was a prespecified and retrospective analysis of all consecutive patients who underwent FFR assessment for intermediate coronary lesions between January 2014 and December 2015. The primary endpoint was defined as the 1-year composite of cardiac death, vessel-related myocardial infarction, and clinically-driven target vessel revascularization. RESULTS: In 1554 lesions (23% in women), FFR was lower in men [0.83 ±0.09 vs 0.85 ±0.08, P = .004] driven by LAD values (for LAD P < .001, LCx or RCA P> .40). In proximal lesions (PLs), FFR was lower in men [0.83 ±0.10 vs 0.85 ±0.08, P = .004] with comparable values in non-PLs [0.84 ±0.09 vs 0.85 ±0.08, P = .36]. In PLs, the primary endpoint was higher in women [HR(adjusted) 3.18 (1.08-9.37), P = .035] with comparable outcomes in non-PLs (P = .032 for interaction). In deferred lesions, the primary endpoint was higher in women [HR(adjusted) 2.73 (1.10-6.74), P = .03] with no differences in revascularized lesions across sex (P = .02 for interaction). Results were consistent when using propensity score matching analysis. CONCLUSIONS: There is a sex-based difference in FFR, particularly in stenoses subtending large myocardium, and more evident in deferred lesions.

Navigator-based reacquisition and estimation of motion-corrupted data: Application to multi-echo spin echo for carotid wall MRI.

PURPOSE: To assess whether artifacts in multi-slice multi-echo spin echo neck imaging, thought to be caused by brief motion events such as swallowing, can be corrected by reacquiring corrupted central k-space data and estimating the remainder with parallel imaging. METHODS: A single phase-encode line (ky = 0, phase-encode direction anteroposterior) navigator echo was used to identify motion-corrupted data and guide the online reacquisition. If motion corruption was detected in the 7 central k-space lines, they were replaced with reacquired data. Subsequently, GRAPPA reconstruction was trained on the updated central portion of k-space and then used to estimate the remaining motion-corrupted k-space data from surrounding uncorrupted data. Similar compressed sensing-based approaches have been used previously to compensate for respiration in cardiac imaging. The g-factor noise amplification was calculated for the parallel imaging reconstruction of data acquired with a 10-channel neck coil. The method was assessed in scans with 9 volunteers and 12 patients. RESULTS: The g-factor analysis showed that GRAPPA reconstruction of 2 adjacent motion-corrupted lines causes high noise amplification; therefore, the number of 2-line estimations should be limited. In volunteer scans, median ghosting reduction of 24% was achieved with 2 adjacent motion-corrupted lines correction, and image quality was improved in 2 patient scans that had motion corruption close to the center of k-space. CONCLUSION: Motion-corrupted echo-trains can be identified with a navigator echo. Combined reacquisition and parallel imaging estimation reduced motion artifacts in multi-slice MESE when there were brief motion events, especially when motion corruption was close to the center of k-space.

Hyper-acute cardiovascular magnetic resonance T1 mapping predicts infarct characteristics in patients with ST elevation myocardial infarction.

BACKGROUND: Myocardial recovery after primary percutaneous coronary intervention in acute myocardial infarction is variable and the extent and severity of injury are difficult to predict. We sought to investigate the role of cardiovascular magnetic resonance T1 mapping in the determination of myocardial injury very early after treatment of ST-segment elevation myocardial infarction (STEMI). METHODS: STEMI patients underwent 3 T cardiovascular magnetic resonance (CMR), within 3 h of primary percutaneous intervention (PPCI). T1 mapping determined the extent (area-at-risk as %left ventricle, AAR) and severity (average T1 values of AAR) of acute myocardial injury, and related these to late gadolinium enhancement (LGE), and microvascular obstruction (MVO). The characteristics of myocardial injury within 3 h was compared with changes at 24-h to predict final infarct size. RESULTS: Forty patients were included in this study. Patients with average T1 values of AAR ≥1400 ms within 3 h of PPCI had larger LGE at 24-h (33% ±14 vs. 18% ±10, P = 0.003) and at 6-months (27% ±9 vs. 12% ±9; P < 0.001), higher incidence and larger extent of MVO (85% vs. 40%, P = 0.016) & [4.0 (0.5-9.5)% vs. 0 (0-3.0)%, P = 0.025]. The average T1 value was an independent predictor of acute LGE (ß 0.61, 95%CI 0.13 to 1.09; P = 0.015), extent of MVO (ß 0.22, 95%CI 0.03 to 0.41, P = 0.028) and final infarct size (ß 0.63, 95%CI 0.21 to 1.05; P = 0.005). Receiver-operating-characteristic analysis showed that T1 value of AAR obtained within 3-h, but not at 24-h, predicted large infarct size (LGE > 9.5%) with 100% positive predictive value at the optimal cut-off of 1400 ms (area-under-the-curve, AUC 0.88, P = 0.006). CONCLUSION: Hyper-acute T1 values of the AAR (within 3 h post PPCI, but not 24 h) predict a larger extent of MVO and infarct size at both 24 h and 6 months follow-up. Delayed CMR scanning for 24 h could not substitute the significant value of hyper-acute average T1 in determining infarct characteristics.

Aspirin Discontinuation in Patients Requiring Oral Anticoagulation Undergoing Percutaneous Coronary Intervention, The Role of Procedural Complexity.

BACKGROUND: The prognostic role of procedural complexity when discontinuing aspirin in patients on oral anticoagulation undergoing percutaneous coronary intervention (PCI) has never been studied. METHODS: Ischaemic events were compared in 256 consecutive patients according to procedural complexity and aspirin on discharge. PCI complexity was defined according to the high-risk features for ischaemic events in the current guidelines RESULTS: Forty percent patients had stable presentation. In patients with complex PCI, ischaemic events were significantly higher when discharged without aspirin (adjusted HR 3.66, (95% CI 1.07 to 12.47), P = 0.038). This was driven from both target vessel failure and de-novo coronary lesions. Ischaemic events were comparable between patients with complex PCI on aspirin and those who underwent non-complex PCI. CONCLUSIONS: Procedural complexity in patients with indication for oral anticoagulation undergoing PCI should be factored in when deciding optimal antithrombotic therapies. Aspirin discontinuation in patients with high-risk PCI features should be discouraged.

Dynamic changes in injured myocardium, very early after acute myocardial infarction, quantified using T1 mapping cardiovascular magnetic resonance.

BACKGROUND: It has recently been suggested that myocardial oedema follows a bimodal pattern early post ST-segment elevation myocardial infarction (STEMI). Yet, water content, quantified using tissue desiccation, did not return to normal values unlike oedema quantified by cardiovascular magnetic resonance (CMR) imaging. We studied the temporal changes in the extent and intensity of injured myocardium using T1-mapping technique within the first week after STEMI. METHODS: A first group (n = 31) underwent 3 acute 3 T CMR scans (time-point (TP) < 3 h, 24 h and 6 days), including cine, native shortened modified look-locker inversion recovery T1 mapping, T2* mapping and late gadolinium enhancement (LGE). A second group (n = 17) had a single scan at 24 h with an additional T2-weighted sequence to assess the difference in the extent of area-at-risk (AAR) compared to T1-mapping. RESULTS: The mean T1 relaxation time value within the AAR of the first group was reduced after 24 h (P < 0.001 for TP1 vs.TP2) and subsequently increased at 6 days (P = 0.041 for TP2 vs.TP3). However, the extent of AAR quantified using T1-mapping did not follow the same course, and no change was detected between TP1&TP2 (P = 1.0) but was between TP2 &TP3 (P = 0.019). In the second group, the extent of AAR was significantly larger on T1-mapping compared to T2-weighted (42 ± 15% vs. 39 ± 15%, P = 0.025). No change in LGE was detected while microvascular obstruction and intra-myocardial haemorrhage peaked at different time points within the first week of reperfusion. CONCLUSION: The intensity of oedema post-STEMI followed a bimodal pattern; while the extent of AAR did not track the same course. This discrepancy has implications for use of CMR in this context and may explain the previously reported disagreement between oedema quantified by imaging and tissue desiccation.

Role of deferred stenting in patients with ST elevation myocardial infarction treated with primary percutaneous coronary intervention: A systematic review and meta-analysis.

OBJECTIVES: We conducted a meta-analysis of studies comparing deferred stenting strategy versus the conventional approach with immediate stenting in patients with ST elevation myocardial infarction. BACKGROUND: Deferring stent after mechanical flow restoration has been proposed as a strategy to reduce the risk of "no reflow" in patients with STEMI undergoing primary percutaneous coronary intervention (pPCI). Conflicting evidence is available currently, especially after the recent publication of three randomized clinical trials. METHODS: Searches in electronic databases were performed. Comparisons between the two strategies were performed for both hard clinical endpoints (all cause-mortality, cardiovascular mortality, unplanned revascularization, myocardial infarction and readmission for heart failure) and surrogate angiographic endpoints (TIMI flow < 3 and myocardial blush grade (MBG) < 2). RESULTS: Eight studies (three randomized and five non-randomized) were deemed eligible, accounting for a total of 2101 patients. No difference in terms of hard clinical endpoints was observed between deferred and immediate stenting (OR [95% CI]: 0.79 [0.54-1.15], for all-cause mortality; odds ratio (OR) [95% CI]: 0.79 [0.47-1.31] for cardiovascular mortality; OR [95% CI]: 0.95 [0.64-1.41] for myocardial infarction; OR [95% CI]: 1.37 [0.87-2.16], for unplanned revascularization and OR [95% CI]: 0.50 [0.21-1.17] for readmission for heart failure). Notably, the deferred stenting approach was associated with improved outcome of the surrogate angiographic endpoints (OR [95% CI]: 0.43 [0.18-0.99] of TIMI flow < 3 and OR [95% CI]: 0.25 [0.11-0.57] for MBG < 2. CONCLUSIONS: A deferred stenting strategy could be a feasible alternative to the conventional approach with immediate stenting in "selected" STEMI patients undergoing pPCI.