Incidence, Predictors, and Prognostic Impact of Neurologic Events After TAVR According to VARC-3 Criteria.

BACKGROUND: The Valve Academic Research Consortium (VARC)-3 definition for neurologic events after transcatheter aortic valve replacement (TAVR) lacks clinical validation. OBJECTIVES: This study sought to determine the incidence, predictors, and clinical impact of neurologic events following TAVR as defined by VARC-3 criteria. METHODS: This was a multicenter study including 2,924 patients with severe aortic stenosis undergoing TAVR. Based on Neurologic Academic Research Consortium (NeuroARC) classification, neurologic events were classified as NeuroARC type 1 (stroke), NeuroARC type 2 (covert central nervous system injury), and NeuroARC type 3 (transient ischemic attack and delirium). Baseline, procedural, and follow-up data were prospectively collected in a dedicated database. RESULTS: After a median follow-up of 13 (7-37) months, neurologic events occurred in 471 patients (16.1%), NeuroARC type 1, 2, and 3 in 37.4%, 4.7%, and 58.0% of cases, respectively, and the majority (58.6%) were periprocedural. Advanced age, chronic kidney disease, atrial fibrillation, major vascular complications, and in-hospital bleeding determined an increased risk of periprocedural events (P < 0.03 for all). Neurologic events occurring during the periprocedural time frame were independently associated with a substantial increase in mortality at 1 year after the intervention (HR: 1.91; 95% CI: 1.23-2.97; P = 0.004). However, although NeuroARC type 1 was associated with an increased mortality risk (IRR: 3.38; 95% CI: 2.30-5.56; P < 0.001 and IRR: 21.7; 95% CI: 9.63-49.1; P < 0.001 for ischemic and hemorrhagic stroke, respectively), the occurrence of NeuroARC type 3 events had no impact on mortality. CONCLUSIONS: Neurologic events after TAVR were associated with poorer short- and long-term survival. This correlation was related to the type of NeuroARC event defined by the VARC-3 criteria. Given the negative impact on clinical outcomes, every attempt should be made to reduce the risk of neurologic complications after TAVR.

Strategies to Minimize Access Site-related Complications in Patients Undergoing Transfemoral Artery Procedures with Large-bore Devices.

Large bore accesses refer to accesses with a diameter of 10 French or greater and are necessary for various medical devices, including those used in transcatheter aortic valve replacement, endovascular aneurysm repair stent-grafts, and percutaneous mechanical support devices. Notably, the utilization of these devices via femoral access is steadily increasing due to advancements in technology and implantation techniques, which are expanding the pool of patients suitable for percutaneous procedures. However, procedures involving large bore devices carry a high risk of bleeding and vascular complications (VCs), impacting both morbidity and long-term mortality. In this review article, we will first discuss the incidence, determinants, and prognostic impact of VCs in patients undergoing large bore access procedures. Subsequently, we will explore the strategies developed in recent years to minimize VCs, including techniques for optimizing vascular puncture through femoral cannulation, such as the use of echo-guided access cannulation and fluoroscopic guidance. Additionally, we will evaluate existing vascular closure devices designed for large bore devices. Finally, we will consider new pharmacological strategies aimed at reducing the risk of periprocedural access-related bleeding.

Bioprosthetic leaflet thrombosis and reduced leaflet motion after transcatheter aortic valve replacement: A systematic review and meta-analysis.

BACKGROUND: Leaflet thrombosis and reduced leaflet motion have become a concern with the expanding use of transcatheter aortic valve replacement in lower-risk patients. AIMS: To assess the proportions, predictors and clinical impact of leaflet thrombosis and reduced leaflet motion after transcatheter aortic valve replacement. METHODS: We performed a meta-analysis of studies assessing the proportions of and/or clinical outcomes according to the presence of leaflet thrombosis after transcatheter aortic valve replacement identified with computed tomography and/or echocardiography. RESULTS: Fifty-three studies, representing 25,258 patients undergoing transcatheter aortic valve replacement, were considered. The proportion of leaflet thrombosis was 5.2% overall, and was higher in computed tomography versus echocardiography (16.4% vs. 1.1%, respectively); reduced leaflet motion was identified in 11% of patients with four-dimensional computed tomography. Intra-annular bioprostheses were associated with a higher proportion of leaflet thrombosis, whereas chronic oral anticoagulation was protective for leaflet thrombosis in both computed tomography and echocardiographic studies (9.7% vs. 17.5%; relative risk [RR]: 0.51, 95% confidence interval [95% CI]: 0.37-0.71 and 0.9% vs. 2.7%; RR: 0.22, 95% CI: 0.06-0.79, respectively) and for reduced leaflet motion (2.5% vs. 12.4%; RR: 0.32, 95% CI: 0.13-0.76). Leaflet thrombosis was not associated with an increased risk of death, but with a higher risk of stroke in computed tomography studies (2.8% vs. 2.4%; RR: 1.63, 95% CI: 1.05-2.55), a difference more pronounced when considering reduced leaflet motion (3.5% vs. 1.7%; RR: 2.39, 95% CI: 0.63-8.34). CONCLUSIONS: The proportion of leaflet thrombosis is highly variable according to the screening approach, the type of valve and the use of oral anticoagulation. The occurrence of cerebral events is increased when leaflet thrombosis and/or reduced leaflet motion are diagnosed, but leaflet thrombosis has no impact on survival.

The Effects of Statins, Ezetimibe, PCSK9-Inhibitors, Inclisiran, and Icosapent Ethyl on Platelet Function.

This review aims to examine the complex interaction between dyslipidemia, platelet function, and related drug treatments. In particular, the manuscript provides an overview of the effects of major hypolipidemic drugs on platelet function. Indeed, growing evidence supports the view that statins, ezetimibe, PCSK9 inhibitors, inclisiran, and icosapent ethyl also act as antithrombotics. It is known that platelets play a key role not only in the acute phase of coronary syndromes but also in the early phase of atherosclerotic plaque formation. The goal of cholesterol-lowering therapy is to reduce cardiovascular events. The direct effects of cholesterol-lowering drugs are widely described in the literature. Lowering LDL-c (low-density lipoprotein cholesterol) by 1 mmol/L results in a 22-23% reduction in cardiovascular risk. Numerous studies have examined the direct antithrombotic effects of these drugs on platelets, endothelium, monocytes, and smooth muscle cells, and thus, potentially independent of blood LDL-cholesterol reduction. We reviewed in vitro and in vivo studies evaluating the complex interaction between hypercholesterolemia, hypertriglyceridemia, platelet function, and related drug treatments. First, we discussed the role of statins in modulating platelet activation. Discontinuation of statin therapy was associated with increased cardiovascular events with increased ox-LDL, P-selectin, and platelet aggregation. The effect of PCSK9-I (inhibitors of proprotein convertase subtilisin/kexin type 9, PCSK9 involved in the degradation of LDL receptors in the liver) was associated with a statistically significant reduction in platelet reactivity, calculated in P2Y12 reaction units (PRU), in the first 14 days and no difference at 30 days compared to placebo. Finally, in patients with hypertriglyceridemia, the REDUCE-IT study showed that icosapent ethyl (an ethyl ester of eicosapentaenoic acid that reduces triglyceride synthesis and improves triglyceride clearance) resulted in a 25% reduction in ischemic events and cardiovascular death. However, to date, there is not yet clear clinical evidence that the direct antithrombotic effects of the drugs may have a beneficial impact on outcomes independently from the reduction in LDL-C or triglycerides.

Cellular and Molecular Mechanisms Underlying Tricuspid Valve Development and Disease.

Tricuspid valve (TV) disease is highly prevalent in the general population. For ages considered "the forgotten valve" because of the predominant interest in left-side valve disease, the TV has now received significant attention in recent years, with significant improvement both in diagnosis and in management of tricuspid disease. TV is characterized by complex anatomy, physiology, and pathophysiology, in which the right ventricle plays a fundamental role. Comprehensive knowledge of molecular and cellular mechanisms underlying TV development, TV disease, and tricuspid regurgitation-related right-ventricle cardiomyopathy is necessary to enhance TV disease understanding to improve the ability to risk stratify TR patients, while also predicting valve dysfunction and/or response to tricuspid regurgitation treatment. Scientific efforts are still needed to eventually decipher the complete picture describing the etiopathogenesis of TV and TV-associated cardiomyopathy, and future advances to this aim may be achieved by combining emerging diagnostic imaging modalities with molecular and cellular studies. Overall, basic science studies could help to streamline a new coherent hypothesis underlying both the development of TV during embryogenesis and TV-associated disease and its complications in adult life, providing the conceptual basis for the ultimate and innovative field of valve repair and regeneration using tissue-engineered heart valves.

Acute expansion of nitinol-based self-expandable device in patients undergoing transfemoral aortic valve implantation.

BACKGROUND: The acute adaptation of the nitinol-based stent frame self expandable valve to the aortic root after deployment is poorly understood. Accordingly, this study aimed to assess the occurrence, degree and determinants of acute adaptation of the nitinol-based stent frame self-expandable valves after implantation. METHODS: This is a single-site prospective registry including patients undergoing transcatheter aortic valve replacement (TAVR) with a widely used second-generation nitinol-based self-expandable device (Evolut R, Medtronic, Minneapolis, Minnesota, USA). We measured valve diameters at three different sections: distal (aortic) level, central (annulus) level and proximal (ventricular) level. Valve expansion was estimated by the difference between the diameters calculated immediately after valve deployment (A) and at the end of the procedure (B). The absolute and relative stent changes were defined as B-A and (B-A)/B∗100, respectively. A linear regression model was performed to test the association between the degree of valve extension at each segment with baseline and procedural characteristics. RESULTS: A total of 58 consecutive TAVR patients were included in this analysis, with a mean age of 82.12 ±â€Š5.28 years. Out of the total, 46% of the patients had chronic kidney disease, 32% had diabetes and 76% had dyslipidaemia. The mean procedural time was 28.11 ±â€Š11.6 min, with 53.45% of predilation. Postdilation was performed only in 3.5% of patients. Final stent diameters were significantly higher than those achieved immediately after valve implantation - an observation that was consistent for all the segments: 0.50 ±â€Š0.51 mm and 2.48 ±â€Š2.57% ( P  < 0.01) in the proximal, 0.46 ±â€Š0.57 mm and 2.39 ±â€Š2.96% ( P  < 0.01) in the central, as well as 0.58 ±â€Š0.59 mm and 2.14 ±â€Š2.14% ( P  < 0.01) at the distal segments. Postdilation significantly affected the expansion of the central segment, and, albeit not significantly, the proximal one, while no changes were observed for the distal portion of the platform. CONCLUSION: This is the first study to have documented a significant degree of the Evolut R self-expandable valve expansion after deployment. However, further studies are required to assess the short- and long-term time course of self-expandable valve enlargement and the clinical relevance of this finding.

Stent Thrombosis and Restenosis with Contemporary Drug-Eluting Stents: Predictors and Current Evidence.

Iterations in stent technologies, advances in pharmacotherapy, and awareness of the implications of implantation techniques have markedly reduced the risk of stent failure, both in the form of stent thrombosis (ST) and in-stent restenosis (ISR). However, given the number of percutaneous coronary interventions (PCI) performed worldwide every year, ST and ISR, albeit occurring at a fairly low rate, represent a public health problem even with contemporary DES platforms. The understanding of mechanisms and risk factors for these two PCI complications has been of fundamental importance for the parallel evolution of stent technologies. Risk factors associated with ST and ISR are usually divided into patient-, lesion-, device- and procedure-related. A number of studies have shown how certain risk factors are related to early (1 month) versus late/very late ST (between 1 month and 1 year and >1 year, respectively). However, more research is required to conclusively show the role of time-dependence of risk factors also in the incidence of ISR (early [1 year] or late [>1 year]). A thorough risk assessment is required due to the complex etiology of ST and ISR. The most effective strategy to treat ST and ISR is still to prevent them; hence, it is crucial to identify patient-, lesion-, device- and procedure-related predictors.

Antithrombotic therapy and cardiovascular outcomes after transcatheter aortic valve implantation in patients without indications for chronic oral anticoagulation: a systematic review and network meta-analysis of randomized controlled trials.

AIMS: As the antithrombotic regimen that may best prevent ischaemic complications along with the lowest bleeding risk offset following transcatheter aortic valve implantation (TAVI) remains unclear, we aimed to compare the safety and efficacy of antithrombotic regimens in patients without having an indication for chronic oral anticoagulation. METHODS AND RESULTS: We conducted a PROSPERO-registered (CRD42021247924) systematic review and network meta-analysis of randomized controlled trials evaluating post-TAVI antithrombotic regimens up to April 2022. We estimated the relative risk (RR) and 95% confidence intervals (95% CIs) using a random-effects model in a frequentist pairwise and network metanalytic approach. We included seven studies comprising 4006 patients with a mean weighted follow-up of 12.9 months. Risk of all-cause death was significantly reduced with dual antiplatelet therapy (DAPT) compared with low-dose rivaroxaban + 3-month single antiplatelet therapy (SAPT) (RR 0.60, 95% CI 0.41-0.88), while no significant reduction was observed with SAPT vs. DAPT (RR 1.02, 95% CI 0.67-1.58) and SAPT and DAPT compared with apixaban or edoxaban (RR 0.60, 95% CI 0.32-1.14 and RR 0.59, 95% CI 0.34-1.02, respectively). SAPT was associated with a significant reduction of life-threatening, disabling, or major bleeding compared with DAPT (RR 0.45, 95% CI 0.29-0.70), apixaban or edoxaban alone (RR 0.45, 95% CI 0.25-0.79), and low-dose rivaroxaban + 3-month SAPT (RR 0.30, 95% CI 0.16-0.57). There were no differences between the various regimens with respect to myocardial infarction, stroke, or systemic embolism. CONCLUSION: Following TAVI in patients without an indication for chronic oral anticoagulant, SAPT more than halved the risk of bleeding compared with DAPT and direct oral anticoagulant-based regimens without significant ischaemic offset.

Simultaneous Radial and Ipsilateral Ulnar Artery Compression versus Isolated Radial Artery Compression after Conventional Radial Access for Coronary Angiography and/or Intervention: A Systematic Review and Meta-Analysis.

Background: Simultaneous ulnar and radial artery compression (SURC) has emerged as a strategy to increase radial artery flow and mitigate radial artery occlusion (RAO) while achieving adequate hemostasis after transradial access (TRA), though its technical adoption has been limited worldwide. Methods: A systematic search of studies comparing SURC versus isolated radial artery compression after TRA for coronary angiography and/or intervention was performed. Data were pooled by meta-analysis using random-effects models. Odds ratios (OR) with relative 95% confidence intervals (CI) and standardized mean difference were used as measures of effect estimates. The primary endpoint was the occurrence of overall RAO. Results: A total of 6 studies and 6793 patients were included. SURC method as compared to isolated radial artery compression was associated with a lower risk of RAO both overall (OR 0.29; 95% CI, 0.13−0.61, p < 0.001; number needed to treat to benefit [NNTB] =38) and in-hospital (OR 0.28; 95% CI: 0.10 to 0.75; p = 0.01, NNTB = 36), with a reduced risk of unsuccessful patent hemostasis (OR: 0.13; 95% CI: 0.02 to 0.85; p = 0.03, NNT = 5) and upper extremity pain (OR: 0.48; 95% CI: 0.24 to 0.95; p = 0.04, NNTB = 124). No significant difference was observed in hemostasis time and in the risk of hematoma. Conclusion: Compared to isolated radial artery compression, SURC is associated with lower risk of RAO, unsuccessful patent hemostasis, and reported upper limb pain, without any trade-off in safety outcomes. With further development of dedicated dual compression devices, the proposed technique should be freed from usage constraints.

Unmet Needs in TAVR: Conduction Disturbances and Management of Coronary Artery Disease.

Over the past two decades, transcatheter aortic valve replacement (TAVR) swiftly evolved from a disrupting technology towards mainstream therapy in the field of severe symptomatic aortic stenosis. A series of randomized evaluations established its role in treating severe aortic stenosis patients across all surgical risk categories, paving the way for an extension of its indications to younger low-risk patients with a longer life expectancy. Therefore, managing comorbidities and limiting procedural complications, which may affect long-term outcomes, is of paramount importance. Among those, new-onset conduction disturbances and concomitant coronary artery disease remain two of the most debated issues. In the present review, we will discuss the incidence, prognostic impact, and unmet needs of patients with post-TAVR new-onset conduction disturbances and the ongoing challenges posed by the management of concomitant coronary artery disease.

Stent Thrombosis After Percutaneous Coronary Intervention: From Bare-Metal to the Last Generation of Drug-Eluting Stents.

Since their introduction in clinical practice in 1986, different types of coronary stents have been developed and become available for the treatment of coronary artery disease. Stent thrombosis (ST) is an uncommon but harmful complication after percutaneous coronary implantation, with a high occurrence of acute myocardial infarction and risk of mortality. Among several procedural and clinical predictors, the type of coronary stent is a strong determinant of ST. This article reviews the available evidence on the most used coronary stent types in the modern era and the related risk of ST.

Acute Kidney Injury After Transcatheter Aortic Valve Replacement Mediates the Effect of Chronic Kidney Disease.

Background Acute kidney injury (AKI) after transcatheter aortic valve replacement (TAVR) is associated with increased mortality. However, it is controversial whether AKI affects prognosis per se, being linked to baseline chronic kidney disease (CKD) and bleeding complications. The aim of this study was to disentangle, applying mediation analysis, the association between AKI and clinical outcome, considering CKD and bleedings. Methods and Results Consecutive patients undergoing TAVR were prospectively enrolled at 5 high-volume centers in Italy. AKI was defined according to Valve Academic Research Consortium-3 consensus, whereas bleeding with Bleeding Academic Research Consortium. Primary outcome was all-cause mortality after 1-year follow-up. Among 2621 patients undergoing TAVR, AKI occurrence was associated with 1-year mortality. This association of AKI with the primary end points remained significant after adjusting for baseline risk estimators, either Society of Thoracic Surgeons score (hazard ratio [HR], 2.78 [95% CI, 1.95-3.80], P<0.001) or EuroSCORE-II (HR, 1.85 [95% CI, 1.35-2.56], P<0.001). Both AKI and CKD significantly and independently affected primary outcome (HR, 3.06 [95% CI, 2.01-4.64], P<0.001 and HR, 1.82 [95% CI 1.27-2.65], P<0.01, respectively). The estimated proportion of the total effect of CKD mediated via AKI was, on average, 15%, 95% CI, 4%-29%, P<0.001. The significant effect of Bleeding Academic Research Consortium 2-5 bleedings on the primary outcome was not mediated by AKI. Conclusions AKI occurs in 1 out of 6 patients and significantly mediates one fifth of the effect of baseline CKD on all-cause mortality after TAVR. Our analysis supports a systematic effort to prevent AKI during TAVR, which may potentially translate into improved patients' 1-year survival.

The Telecardiology Revolution: From Emergency Management to Daily Clinical Practice.

AIMS: Telecardiology is one of the most widespread applications of telemedicine. We aimed to report the design and development of a telecardiology system in the sanitary district of Cosenza, one of the largest in Italy, with a complex orography, and healthcare reorganization needs, for the management of the emergency network and daily clinical practice. METHODS: Our telecardiology network connects 8 hospitals, 9 first aid centers, 20 local 118-EMS stations, 1 helicopter station, 8 hospital emergency departments, 59 hospital departments, and 3 catheterization laboratories. All data are centralized on a dedicated server, accessible from any location for real-time assessment. The quality, source, and timing of the electrocardiograms transmitted were evaluated. RESULTS: From October 2015 to December 2019, a total of 389,970 ECGs were transmitted. The quality of ECGs was optimal in 52%, acceptable in 42%, and poor in 6% of the cases. The number of poor-quality ECGs was only 3% in the last 2 years. Out of the total, 145,097 (37.2%) were transmitted from the emergency departments and 5318 (1.4%) from the 118-EMS. Of interest, a sizable part of the ECG was related to routine clinical practice, comprising 110,556 (28.3%) from the cardiology department and 79,256 (20.3%) from other noncardiovascular departments. Finally, the average reporting time was significantly decreased compared to reporting times without a telecardiology system (5-10 vs. 45-90 min). CONCLUSION: Our telecardiology system provides efficient cardiology assistance for all types, settings, and phases of cardiovascular diseases.

Non-Invasive Myocardial Work in Patients with Severe Aortic Stenosis.

Changes in cardiac mechanics after correction of severe Aortic Stenosis (AS) are under-investigated. Myocardial Work (MW) is emerging as a useful non-invasive correlate of invasively measured myocardial performance and oxygen consumption. The aim of this study was to assess the usefulness of MW in the clinical management of patients with AS undergoing transcatheter aortic valve implantation (TAVI). Consecutive patients referred for TAVI were included in this observational study. Echocardiograms were performed before and after TAVI to measure Global Work Index (GWI), Global Constructive Work (GCW), Global Wasted Work (GWW), and Global Work Efficiency (GWE). Mean transvalvular gradient was significantly improved (p < 0.05), without significant changes in left ventricular ejection fraction, nor in global longitudinal strain (GLS). GWI (p < 0.001) and GCW (p < 0.001), but not GWW (p = 0.241) nor GWE (p = 0.854) were significantly reduced after TAVI. Patients with a low flow low gradient (LF-LG) AS had lower left ventricular ejection fraction (LVEF) (p < 0.001), worse global longitudinal strain (GLS) (p < 0.001), and lower baseline GWI (p < 0.001), GCW (p < 0.001) and GWE (p = 0.003). The improvement in GWI and GCW observed after TAVI in the general study population were abolished among LF-LG patients. In conclusion, non-invasive MW might be useful to further classify patients with AS and to predict non responders.

Flow-Responsive Noncoding RNAs in the Vascular System: Basic Mechanisms for the Clinician.

The vascular system is largely exposed to the effect of changing flow conditions. Vascular cells can sense flow and its changes. Flow sensing is of pivotal importance for vascular remodeling. In fact, it influences the development and progression of atherosclerosis, controls its location and has a major influx on the development of local complications. Despite its importance, the research community has traditionally paid scarce attention to studying the association between different flow conditions and vascular biology. More recently, a growing body of evidence has been accumulating, revealing that ncRNAs play a key role in the modulation of several biological processes linking flow-sensing to vascular pathophysiology. This review summarizes the most relevant evidence on ncRNAs that are directly or indirectly responsive to flow conditions to the benefit of the clinician, with a focus on the underpinning mechanisms and their potential application as disease biomarkers.

Efficacy and safety of alirocumab and evolocumab: a systematic review and meta-analysis of randomized controlled trials.

AIMS: The effect of low-density lipoprotein cholesterol-lowering therapy with alirocumab or evolocumab on individual clinical efficacy and safety endpoints remains unclear. We aimed to evaluate the efficacy and safety of alirocumab and evolocumab in patients with dyslipidaemia or atherosclerotic cardiovascular disease. METHODS AND RESULTS: We performed a review of randomized controlled trials (RCTs) comparing treatment with alirocumab or evolocumab vs. placebo or other lipid-lowering therapies up to March 2018. Primary efficacy endpoints were all-cause death, cardiovascular death, myocardial infarction (MI), and stroke. We estimated risk ratios (RR) and 95% confidence intervals (CI) using random effect models. We included 39 RCTs comprising 66 478 patients of whom 35 896 were treated with proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors (14 639 with alirocumab and 21 257 with evolocumab) and 30 582 with controls. Mean weighted follow-up time across trials was 2.3 years with an exposure time of 150 617 patient-years. Overall, the effects of PCSK9 inhibition on all-cause death and cardiovascular death were not statistically significant (P = 0.15 and P = 0.34, respectively). Proprotein convertase subtilisin-kexin type 9 inhibitors were associated with lower risk of MI (1.49 vs. 1.93 per 100 patient-year; RR 0.80, 95% CI 0.74-0.86; I  2 = 0%; P < 0.0001), ischaemic stroke (0.44 vs. 0.58 per 100 patient-year; RR 0.78, 95% CI 0.67-0.89; I  2 = 0%; P = 0.0005), and coronary revascularization (2.16 vs. 2.64 per 100 patient-year; RR 0.83, 95% CI 0.78-0.89; I  2 = 0%; P < 0.0001), compared with the control group. Use of these PCSK9 inhibitors was not associated with increased risk of neurocognitive adverse events (P = 0.91), liver enzymes elevations (P = 0.34), rhabdomyolysis (P = 0.58), or new-onset diabetes mellitus (P = 0.97). CONCLUSION: Proprotein convertase subtilisin-kexin type 9 inhibition with alirocumab or evolocumab was associated with lower risk of MI, stroke, and coronary revascularization, with favourable safety profile.

New Antithrombotic Strategies and Coronary Stent Technologies for Patients at High Bleeding Risk Undergoing Percutaneous Coronary Intervention.

Patients at High Bleeding Risk (HBR) are a sizable part of the population undergoing Percutaneous Coronary Intervention (PCI) and stent implantation. This population historically lacks standardized definition, thus limiting trial design, data generalizability, and clinical decision-- making. To overcome this limitation, the Academic Research Consortium (ARC) has recently released comprehensive guidelines defining HBR criteria for study design purposes and daily clinical practices. Furthermore, several risk scores have been developed aiming to discriminate against HBR patients and support physicians for clinical decision-making when faced with this complex subset of patients. Accordingly, the first part of this review article will explore guideline-recommended risk scoring as well as ARC-HBR criteria and their relative application for daily clinical practice. The second part of this review article will explore the complex interplay between the risk of bleeding and coronary thrombotic events in patients deemed at HBR. Indeed, several features that identify these patients are also independent predictors of recurrent ischemic events, thus challenging revascularization strategies and optimal antithrombotic therapy. Accordingly, several clinical trials have been conducted to evaluate the safety and efficacy of the new generation of coronary platforms and different antithrombotic strategies for HBR patients to minimize both ischemic and bleeding events. Accordingly, in this part, we discuss current guidelines, trials, and observational data evaluating antithrombotic strategies and stent technologies for patients at HBR.

White blood cell count and clinical outcomes after left main coronary artery revascularization: insights from the EXCEL trial.

BACKGROUND: Prior studies have reported an association between elevated white blood cell count (WBCc) and worse clinical outcomes after coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI). We assessed the prognostic impact of WBCc in patients undergoing revascularization for left main coronary artery disease (LMCAD). METHODS: In Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL), 1905 patients with LMCAD and low or intermediate SYNTAX scores were randomized to PCI with everolimus-eluting stents versus CABG. The 1895 patients with baseline WBCc available were grouped in tertiles of WBCc (mean 5.6 ± 0.8, 7.5 ± 0.5, and 10.1 ± 1.6 × 109/L). RESULTS: Five-year rates of the primary endpoint (death, myocardial infarction or stroke) were similar across increasing WBCc tertiles (21.2, 18.9, and 21.6%; P = 0.46). Individual components of the primary endpoint, Bleeding Academic Research Consortium (BARC) 3-5 bleeding, stent thrombosis or graft occlusion and ischemia-driven revascularization were all similar across WBCc tertiles. By multivariable analysis, WBCc as a continuous variable was not an independent predictor of adverse events (hazard radio per 1 × 109/L: 1.02; 95% CI, 0.97-1.08; P = 0.43). Results were consistent in the PCI and CABG arms individually. CONCLUSION: There was no association between baseline WBCc and 30-day or 5-year clinical outcomes after PCI or CABG. The absence of a clear incremental increase in events with increasing WBCc in the current analysis indicates that WBCc should not routinely be used as a prognostic marker or to guide revascularization decisions in patients with LMCAD.

Prediction of Significant Coronary Artery Disease Through Advanced Echocardiography: Role of Non-invasive Myocardial Work.

Background: Non-invasive prediction of critical coronary artery stenosis (CAST) in patients with coronary artery disease (CAD) is challenging. Strain parameters can often capture an impairment of regional longitudinal function; however, they are load dependent. A novel non-invasive method to estimate Myocardial Work (MW) has been recently proposed, showing a strong correlation with invasive work measurements. Our aim was to investigate the ability of non-invasive MW to predict the ischaemic risk area underlying a CAST. Methods and Results: The study population comprises 80 individuals: 50 patients with CAST and 30 controls (CTRL). Echocardiography recordings were obtained before coronary angiography to measure global longitudinal strain (GLS), Myocardial Work Index (MWI), Myocardial Constructive Work (MCW), Myocardial Wasted work (MWW), Myocardial Work Efficiency (MWE). Global MWI (p = 0.048), MWE (p < 0.001), and MCW (p = 0.048) at baseline were significantly reduced in patients with CAST compared to controls (p < 0.05). Regional MWE within the myocardial segments underlying the CAST, but not LS, was significantly reduced compared to non-target segments (p < 0.001). At ROC analysis, the diagnostic performance to predict CAST for regional MWE (AUC = 0.920, p < 0.001) was higher compared to both regional post-systolic shortening index (PSI) (AUC = 0.600, p = 0.129) and regional LS (AUC = 0.546, p = 0.469). Conclusions: Non-invasive estimation of MW work indices is able to predict a CAST before invasive angiography.