Impact of endothelial shear stress on coronary atherosclerotic plaque progression and composition: A meta-analysis and systematic review.

BACKGROUND AND AIMS: Intracoronary pressure gradients and translesional flow patterns have been correlated with coronary plaque progression and lesion destabilization. In this study, we aimed to determine the relationship between endothelial shear stress and plaque progression and to evaluate the effect of shear forces on coronary plaque features. METHODS: A systematic review was conducted in medical on-line databases. Selected were studies including human participants who underwent coronary anatomy assessment with computational fluid dynamics (CFD)-based wall shear stress (WSS) calculation at baseline with anatomical evaluation at follow-up. A total of six studies were included for data extraction and analysis. RESULTS: The meta-analysis encompassed 31'385 arterial segments from 136 patients. Lower translesional WSS values were significantly associated with a reduction in lumen area (mean difference -0.88, 95% CI -1.13 to -0.62), an increase in plaque burden (mean difference 4.32, 95% CI 1.65 to 6.99), and an increase in necrotic core area (mean difference 0.02, 95% CI 0.02 to 0.03) at follow-up imaging. Elevated WSS values were associated with an increase in lumen area (mean difference 0.78, 95% CI 0.34 to 1.21) and a reduction in both fibrofatty (mean difference -0.02, 95% CI -0.03 to -0.01) and fibrous plaque areas (mean difference -0.03, 95% CI -0.03 to -0.03). CONCLUSION: This meta-analysis shows that WSS parameters were related to vulnerable plaque features at follow-up. These results emphasize the impact of endothelial shear forces on coronary plaque growth and composition. Future studies are warranted to evaluate the role of WSS in guiding clinical decision-making.

An innovative artificial intelligence-based method to compress complex models into explainable, model-agnostic and reduced decision support systems with application to healthcare (NEAR).

BACKGROUND AND OBJECTIVE: In everyday clinical practice, medical decision is currently based on clinical guidelines which are often static and rigid, and do not account for population variability, while individualized, patient-oriented decision and/or treatment are the paradigm change necessary to enter into the era of precision medicine. Most of the limitations of a guideline-based system could be overcome through the adoption of Clinical Decision Support Systems (CDSSs) based on Artificial Intelligence (AI) algorithms. However, the black-box nature of AI algorithms has hampered a large adoption of AI-based CDSSs in clinical practice. In this study, an innovative AI-based method to compress AI-based prediction models into explainable, model-agnostic, and reduced decision support systems (NEAR) with application to healthcare is presented and validated. METHODS: NEAR is based on the Shapley Additive Explanations framework and can be applied to complex input models to obtain the contributions of each input feature to the output. Technically, the simplified NEAR models approximate contributions from input features using a custom library and merge them to determine the final output. Finally, NEAR estimates the confidence error associated with the single input feature contributing to the final score, making the result more interpretable. Here, NEAR is evaluated on a clinical real-world use case, the mortality prediction in patients who experienced Acute Coronary Syndrome (ACS), applying three different Machine Learning/Deep Learning models as implementation examples. RESULTS: NEAR, when applied to the ACS use case, exhibits performances like the ones of the AI-based model from which it is derived, as in the case of the Adaptive Boosting classifier, whose Area Under the Curve is not statistically different from the NEAR one, even the model's simplification. Moreover, NEAR comes with intrinsic explainability and modularity, as it can be tested on the developed web application platform (https://neardashboard.pythonanywhere.com/). CONCLUSIONS: An explainable and reliable CDSS tailored to single-patient analysis has been developed. The proposed AI-based system has the potential to be used alongside the clinical guidelines currently employed in the medical setting making them more personalized and dynamic and assisting doctors in taking their everyday clinical decisions.

Safety and efficacy of drug-eluting stents for patients at high risk of bleedings: A network meta-analysis.

INTRODUCTION: Among different coronary stents implanted in High Bleeding Risk (HBR) patients with an indication for short antiplatelet therapy, no comparisons in terms of efficacy have been provided. METHODS: A Network Meta Analysis was performed including all randomized controlled trials comparing different coronary stents evaluated in HBR patients. Major Adverse Cardiovascular Events (MACEs) as defined by each included trial were the primary end point, whereas TLR (target lesion revascularization), TVR (target vessel revascularization), stent thrombosis and total and major (BARC3-5) bleedings were the secondary ones. RESULTS: A total of four studies (ONYX ONE, LEADERS FREE, SENIOR and HBR in BIO-RESORT) including 6637 patients were analyzed with different kind of stents and dual antiplatelet therapy (DAPT) length (1 or 6 months) on 12 months follow-up. About one-third of these patients were defined HBR due to indication for oral anticoagulation. All drug eluting stents (DESs) reduced risk of MACE compared to Bare Metal Stents (BMSs) when followed by a 1-month DAPT. At SUCRA analysis, Orsiro was the device with the highest probability of performing best. Rates of TLR and TVR were significantly lower when using Resolute Onyx, Synergy and BioFreedom stents in comparison to BMS when followed by 1-month DAPT, with Synergy ranking best. Synergy also showed a significantly lower number of stent thrombosis compared to BMS (RR 0.28, 95% CI 0.06-0.93), while Orsiro and Resolute Integrity showed the highest probability of performing best. CONCLUSION: In HBRs patients, all DESs were superior to BMSs in terms of efficacy and safety. Among DESs, Orsiro was the one with the highest ranking in terms of MACE, mainly driven by a reduced incidence of repeated revascularization and stent thrombosis.

Sex-based analysis of NSTEMI processes of care and outcomes by hospital: a nationwide cohort study.

BACKGROUND: Contemporary studies demonstrate that non-ST-segment elevation myocardial infarction (NSTEMI) processes of care vary according to sex. Little is known regarding variation in practice between geographical areas and centers. METHODS: We identified 305 014 NSTEMI admissions in the United Kingdom (UK) Myocardial Infarction National Audit Project (MINAP), 2010-2017, including female sex (110 209). Hierarchical, multivariate logistic regression models were fitted assessing for differences in primary outcomes according to sex. Risk standardized mortality rates (RSMR) were calculated for individual hospitals to illustrate correlation with variables of interest. 'Heat-maps' were plotted to show regional and sex-based variation in opportunity-based quality-indicator score (surrogate for optimal processes of care). RESULTS: Women presented older (77y vs. 69y, P < 0.001) and were more often Caucasian (93% vs. 91%, P < 0.001). Women were less frequently managed with an invasive coronary angiogram (ICA) (58% vs. 75%, P < 0.001) or percutaneous coronary intervention (PCI) (35% vs. 49%, P < 0.001)). In our hospital-clustered analysis, we show positive correlation between the RSMR and increasing proportion of women treated for NSTEMI (R2 = 0.17, P < 0.001). There was clear negative correlation between proportion of women who had an optimum OBQI score during their admission and RSMR (R2 = 0.22, P < 0.001), with weaker correlation in men (R2 = 0.08, P < 0.001). Heat-maps according to clinical commissioning group (CCG) demonstrate significant regional variation in OBQI score, with women receiving poorer quality care throughout the UK. CONLUSION: There was a significant in variation of the management of patients with NSTEMI according to sex, with widespread geographical variation. Structural changes are required to enable improved care for women.

Obstetric echodynamics: Approaching a new field of multidisciplinary action.

Maternal cardiovascular adaptation during pregnancy is essential for fetal development. Structural and functional changes, including increased blood volume, heart rate, and myocardial hypertrophy, are crucial for optimal tissue perfusion. Recent evidence supports viewing maternal and fetal cardiovascular systems as a unified functional unit, emphasizing the significance of hemodynamic evaluation in pregnancy. Some obstetrical syndromes result from maladaptive maternal cardiovascular responses. Non-invasive hemodynamic tests, like transthoracic echocardiography, aid in distinguishing phenotypes, guiding tailored management strategies for hypertensive disorders. Establishing obstetric hemodynamics as a multidisciplinary field, termed "Obstetric Echodynamics," promises improved clinical care through standardized practices, interdisciplinary cooperation, and enhanced education.

Long-term impact of intravascular ultrasound-guidance for percutaneous coronary intervention on unprotected left main. The IMPACTUS-LM, an observational, multicentric study.

INTRODUCTION: The potential benefit on long term outcomes of Percutaneous Coronary Intervention (PCI) on Unprotected Left Main (ULM) driven by IntraVascular UltraSound (IVUS) remains to be defined. METHODS: IMPACTUS LM-PCI is an observational, multicenter study that enrolled consecutive patients with ULM disease undergoing coronary angioplasty in 13 European high-volume centers from January 2002 to December 2015. Major Adverse Cardiovascular Events (MACEs) a composite of cardiovascular (CV) death, target vessel revascularization (TVR) and myocardial infarction (MI) were the primary endpoints, while its single components along with all cause death the secondary ones. RESULTS: 627 patients with ULM disease were enrolled, 213 patients (34%) underwent IVUS-guided PCI while 414 (66%) angioguided PCI. Patients in the two cohorts had similar prevalence of risk factors except for active smoking and clinical presentation. During a median follow-up of 7.5 years, 47 (22%) patients in the IVUS group and 211 (51%) in the angio-guided group underwent the primary endpoint (HR 0.42; 95% CI [0.31-0.58] p < 0.001). After multivariate adjustment, IVUS was significantly associated with a reduced incidence of the primary endpoint (adj HR 0.39; 95% CI [0.23-0.64], p < 0.001), mainly driven by a reduction of TVR (ad HR 0.30, 95% CI [0.15-0.62], p = 0.001) and of all-cause death (adj HR 0.47, 95% CI [0.28-0.82], p = 0.008). IVUS use, age, diabetes, side branch stenosis, DES and creatinine at admission were independent predictors of MACE. CONCLUSIONS: In patients undergoing ULM PCI, the use of IVUS was associated with a reduced risk at long-term follow-up of MACE, all-cause death and subsequent revascularization.

Contemporary outcomes of chronic total occlusion percutaneous coronary intervention in Europe: the ERCTO registry.

BACKGROUND: Percutaneous coronary interventions (PCI) of chronic total occlusions (CTO) have reached high procedural success rates thanks to dedicated equipment, evolving techniques, and worldwide adoption of state-of-the-art crossing algorithms. AIMS: We report the contemporary results of CTO PCIs performed by a large European community of experienced interventionalists. Furthermore, we investigated the impact of different risk factors for procedural major adverse cardiac and cerebrovascular events (MACCE) and trends of employment of specific devices like dual lumen microcatheters, guiding catheter extensions, intravascular ultrasound and calcium-modifying tools. METHODS: We evaluated data from 8,673 CTO PCIs included in the European Registry of Chronic Total Occlusion (ERCTO) between January 2021 and October 2022. RESULTS: The overall technical success rate was 89.1% and was higher in antegrade as compared with retrograde cases (92.8% vs 79.3%; p<0.001). Compared with antegrade procedures, retrograde procedures had a higher complexity of attempted lesions (Japanese CTO [J-CTO] score: 3.0±1.0 vs 1.9±1.2; p<0.001), a higher procedural and in-hospital MACCE rate (3.1% vs 1.2%; p<0.018) and a higher perforation rate with and without tamponade (1.5% vs 0.4% and 8.3% vs 2.1%, respectively; p<0.001). As compared with mid-volume operators, high-volume operators had a higher technical success rate in antegrade and retrograde procedures (93.4% vs 91.2% and 81.5% vs 69.0%, respectively; p<0.001), and had a lower MACCE rate (1.47% vs 2.41%; p<0.001) despite a higher mean complexity of the attempted lesions (J-CTO score: 2.42±1.28 vs 2.15±1.27; p<0.001). CONCLUSIONS: The adoption of different recanalisation techniques, operator experience and the use of specific devices have contributed to a high procedural success rate despite the high complexity of the lesions documented in the ERCTO.

Increased prevalence of high-risk coronary plaques in metabolic dysfunction associated stetatotic liver disease patients: A meta-analysis.

BACKGROUND: Metabolic dysfunction associated steatotic liver disease (MASLD) is associated with an increased risk of coronary artery disease. Computed Tomography Coronary Angiography (CTCA) can assess both the extent and the features of coronary plaques. We aimed to gather evidence about the prevalence and features of coronary plaques among MASLD patients. METHODS: PubMed, Scopus, and Google Scholar databases were searched for randomized controlled trials and adjusted observational studies assessing the prevalence and features of coronary plaques by means of CTCA in MASLD patients as compared with a control group. The prevalence of coronary stenosis (defined as >30% and >50% diameter of stenosis), of increasing coronary artery calcium (CAC) score and of high-risk features (namely low-attenuation plaques, napkin ring sign, spotty calcification and positive remodelling) in MASLD patients were the endpoints of interest. RESULTS: Twenty-four observational studies were included. MASLD was associated with an increased prevalence of critical coronary stenosis compared with controls (odds ratio [OR] 1.54, 95%CI 1.23-1.93). Increased values of CAC score were observed in MASLD patients (OR 1.35, 95%CI 1.02-1.78 and OR 2.26, 95%CI 1.57-3.23 for CAC score 0-100 and >100, respectively). An increased risk of 'high-risk' coronary plaques was observed in MASLD patients (OR 2.13, 95%CI 1.42-3.19). As high-risk features plaques, a higher prevalence of positive remodelling and spotty calcification characterize MASLD patients (OR 2.92, 95%CI 1.79-4.77 and OR 2.96, 95%CI 1.22-7.20). CONCLUSIONS: Patients with MASLD are at increased risk of developing critical coronary stenosis and coronary plaques characterized by high-risk features as detected by CTCA.

Ultrasound-Assisted, Catheter-Directed Thrombolysis for Acute Intermediate/High-Risk Pulmonary Embolism: Design of the Multicenter USAT IH-PE Registry and Preliminary Results.

Catheter-based revascularization procedures were developed as an alternative to systemic thrombolysis for patients with intermediate-high- and high-risk pulmonary embolisms. USAT IH-PE is a retrospective and prospective multicenter registry of such patients treated with ultrasound-facilitated, catheter-directed thrombolysis, whose preliminary results are presented in this study. The primary endpoint was the incidence of pulmonary hypertension (PH) at follow-up. Secondary endpoints were short- and mid-term changes in the echocardiographic parameters of right ventricle (RV) function, in-hospital and all-cause mortality, and procedure-related bleeding events. Between March 2018 and July 2023, 102 patients were included. The majority were at intermediate-high-risk PE (86%), were mostly female (57%), and had a mean age of 63.7 ± 14.5 years, and 28.4% had active cancer. Echocardiographic follow-up was available for 70 patients, and in only one, the diagnosis of PH was confirmed by right heart catheterization, resulting in an incidence of 1.43% (CI 95%, 0.036-7.7). RV echocardiographic parameters improved both at 24 h and at follow-up. In-hospital mortality was 3.9% (CI 95%, 1.08-9.74), while all-cause mortality was 11% (CI 95%, 5.4-19.2). Only 12% had bleeding complications, of whom 4.9% were BARC ≥ 3. Preliminary results from the USAT IH-PE registry showed a low incidence of PH, improvement in RV function, and a safe profile.

Intravascular ultrasound-guided STAR 2.0: A new technique for chronic total occlusion recanalization.

The use of the subintimal space has allowed a massive advancement in the field of chronic total occlusion percutaneous coronary intervention (PCI). The STAR technique is the first of subintimal techniques. Despite a high acute success rate, follow-up results showed unfavorable outcomes with half of the treated patients showing restenosis/reocclusion at 6 months. We present three cases in which a modification of the STAR technique guided by intravascular ultrasound (IVUS), namely the STAR 2.0, was used as a bailout for successful PCI of chronic total occlusions.

Comparison of mid-term mortality after surgical, supported or unsupported percutaneous revascularization in patients with severely reduced ejection fraction: A direct and network meta-analysis of adjusted observational studies and randomized-controlled.

INTRODUCTION: The optimal revascularization strategy in patients with heart failure with reduced ejection fraction (HFrEF) remains to be elucidated. The aim of this paper is to compare the mid-term mortality rate among patients with severely reduced ejection fraction (EF) and complex coronary artery disease who underwent coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI) with Impella support, or without. METHODS: Randomized control trials and propensity-adjusted observational studies including patients with ischemic cardiomyopathy (ICM) and severe EF reduction undergoing revascularization were selected. Different revascularization strategies (CABG, supported PCI, and PCI without Impella) were compared in pairwise and network meta-analysis. The primary endpoint was mid-term mortality (within the first year after revascularization). RESULTS: Fifteen studies, mostly observational (17,841 patients; 6779 patients treated with CABG, 8478 treated with PCI without Impella, and 2584 treated with Impella-supported PCI) were included in this analysis. The median age was 67.8 years (IQR 65-70.1), 21.2% (IQR 16.4-26%) of patients were female sex, and a high prevalence of cardiovascular risk factors was noted across the entire population. At pairwise analysis, CABG and PCI without Impella showed similar one-year all-cause mortality (10.6% [IQR 7.5-12.6%] vs 12% [IQR 8.4-11.5%]) RR 0.85 CI 0.67-1.09, while supported PCI reduced one-year all-cause mortality compared to PCI without Impella (9.4% [IQR 5.7-12.5%] vs 10.6% [IQR 8.9-10.7%]) RR 0.77 CI 0.6-0.89. At network meta-analysis, supported PCI showed better results (RR 0.75, 95% CI 0.59-0.94) compared to CABG. CONCLUSION: Our analysis found that supported PCI may have a benefit over standard PCI in patients in direct comparison, and over CABG from indirect comparison, and with HFrEF undergoing revascularization. Further RCTs are needed to confirm this result. (PROSPERO CRD42023425667).

Timing and treatment strategies according to SCAI classification in cardiogenic shock.

In patients with cardiogenic shock (CS), particularly those with acute myocardial infarction (AMI), evidence suggests that timely diagnosis and treatment interventions are critical in the prevention of haemo-metabolic compromise. Temporary mechanical circulatory support (tMCS) has shown potential in facilitating revascularization and recovery of patients with acute myocardial infarction cardiogenic shock (AMI-CS). Timing of treatment strategies for CS patients needs to be optimized for use of tMCS devices that are applicable to this heterogeneous patient population. Here, the latest evidence as well as the gaps in knowledge surrounding the role of time in the management of patients with CS is summarized.

From medical therapy to mechanical support: strategies for device selection and implantation techniques.

Cardiogenic shock (CS) is a complex clinical syndrome with a high risk of mortality. The recent, rapid development of temporary mechanical circulatory support (tMCS) has altered CS treatment. While catecholamines remain the cornerstone of CS therapy, tMCS usage has increased. According to shock severity, different treatment strategies including catecholamines alone, catecholamines and tMCS, or multiple tMCS might be used. State-of-the-art implantation techniques are necessary to avoid complications linked to the invasive nature of tMCS. In particular, bleeding and access-site complications might counteract the potential haemodynamic benefit of a percutaneous ventricular assist device. In this review, we describe the role of catecholamines in CS treatment and present the different tMCS devices with an explanation on how to use them according to CS aetiology and severity. Finally, an overview of the best practice for device implantation is provided.

Safety and efficacy of bempedoic acid: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND AND AIMS: Bempedoic Acid (BA) is a novel Lipid-Lowering Therapy (LLT). We performed a systematic review and meta-analysis to assess the efficacy and safety of BA in patients with hypercholesterolemia. METHODS: PubMed, Scopus, and Cochrane library databases were searched for randomised controlled trials evaluating the efficacy and/or safety of BA compared with placebo. Trials investigating dosages other than 180 mg/die were excluded. Major adverse cardiovascular events (MACE) were the primary efficacy endpoint. LDL-cholesterol reduction was the primary laboratory endpoint. Pre-specified safety endpoints included muscle-related adverse events, new-onset diabetes, and gout. The protocol was registered on PROSPERO (temporary ID:399,867). RESULTS: Study search identified 275 deduplicated results. 11 studies, encompassing 18,315 patients (9854 on BA vs 8461 on placebo/no treatment) were included. BA was associated with a reduced risk of MACE (OR 0.86, 95% CI 0.79-0.95), myocardial infarction (OR 0.76, 95% CI 0.64-0.88) and unstable angina (OR 0.69, 95% CI 0.54-0.88) compared to control, over a median follow up of 87 (15-162) weeks. BA was associated with a reduction of LDL-Cholesterol (mean difference [MD]-22.42,95% CI - 24.02% to - 20.82%), total cholesterol (- 16.50%,95% - 19.21% to - 13.79%), Apo-B lipoprotein (- 19.55%, - 22.68% to - 16.42%) and high-sensitivity CRP (- 27.83%, - 31.71% to - 23.96%) at 12 weeks. BA was associated with a higher risk of gout (OR 1.55, 95% CI 1.27-1.90) as compared with placebo. Efficacy on laboratory endpoints was confirmed, with a variable extent, across patients on statin or ezetimibe background therapy. CONCLUSIONS: The improved cholesterol control achieved with BA translates into a reduced risk of MACE, including myocardial infarction and coronary revascularisation. The drug has a satisfactory safety profile except for an increased risk of gout.

Coronary Plaque Characteristics Associated With Major Adverse Cardiovascular Events in Atherosclerotic Patients and Lesions: A Systematic Review and Meta-Analysis.

BACKGROUND: The clinical value of high-risk coronary plaque characteristics (CPCs) to inform intensified medical therapy or revascularization of non-flow-limiting lesions remains uncertain. OBJECTIVES: The authors performed a systematic review and meta-analysis to study the prognostic impact of CPCs on patient-level and lesion-level major cardiovascular adverse events (MACE). METHODS: Thirty studies (21 retrospective, 9 prospective) with 30,369 patients evaluating the association of CPCs with MACE were included. CPCs included high plaque burden, low minimal lumen area, thin cap fibroatheroma, high lipid core burden index, low-attenuation plaque, spotty calcification, napkin ring sign, and positive remodeling. RESULTS: CPCs were evaluated with the use of intracoronary modalities in 9 studies (optical coherence tomography in 4 studies, intravascular ultrasound imaging in 3 studies, and near-infrared spectroscopy intravascular ultrasound imaging in 2 studies) and by means of coronary computed tomographic angiography in 21 studies. CPCs significantly predicted patient-level and lesion-level MACE in both unadjusted and adjusted analyses. For most CPCs, accuracy for MACE was modest to good at the patient level and moderate to good at the lesion level. Plaques with more than 1 CPC had the highest accuracy for lesion-level MACE (AUC: 0.87). Because the prevalence of CPCs among plaques was low, estimated positive predictive values for lesion-level MACE were modest. Results were mostly consistent across imaging modalities and clinical presentations, and in studies with prevailing hard outcomes. CONCLUSIONS: Characterization of CPCs identifies high-risk atherosclerotic plaques that place lesions and patients at risk for future MACE, albeit with modest sensitivity and positive predictive value (Coronary Plaque Characteristics Associated With Major Adverse Cardiovascular Events Among Atherosclerotic Patients and Lesions; CRD42021251810).