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Women present specific risks for transcatheter aortic valve replacement (TAVI) but there are scarce sex-based analysis. The aim of this study was to explore the risk of vascular/bleeding complications in females vs. males that underwent TAVI and the impact of red blood cell (RBC) transfusion. TRITAVI-Women is a retrospective analysis in 13 European institutions. Propensity score based on pairs of different sex was performed and global outcomes, vascular/bleeding risk factors were determined. Afterwards, the female population of the study was divided into two groups according to the need of RBC transfusion and the risk for mortality, AKI, MI, stroke at 30-days and at 1-year were compared as a combined endpoint (primary endpoint) and separately (secondary endpoints). The global study population included 5837 patients. Females presented more advanced NYHA class, chronic kidney disease, and baseline anemia. Vascular/bleeding complications and RBC transfusion were more common in women. However, 1-year mortality was lower for women in the matched cohort (8.1% vs.10.3%, p = 0.028). The need for RBC transfusion was an independent predictor of higher incidence of the primary endpoint at 30-day and 1-year. The main predictor of RBC transfusion in women was the presence of baseline anemia. Women present lower risk of mortality than men at 1-year follow up, but not at 30-day due to higher rates of vascular/bleeding complications. RBC transfusion was also more often required in women and was an independent predictor or poorer outcomes. The treatment of pre-existing anemia before TAVI might improve the short-term results in women. • Women present similar 30-days risk of mortality compared to men after transcatheter aortic valve implantation. • Women present lower 1-year risk of mortality compared to men after transcatheter aortic valve implantation. • Greater rate of vascular/bleeding complications, and RCB transfusion might explain worse outcomes of women at short-term. • Baseline anemia was more common in women and predicted a greater need for RBC transfusion. [ABSTRACT FROM AUTHOR]

Background: The benefit of percutaneous mitral valve repair (PMVR) in patients with secondary MR is still debated. We aimed to compare the outcome of PMVR with optimal medical therapy (OMT) versus OMT alone in patients with secondary mitral regurgitation (MR) and to assess the role of potential effect modifiers.Methods: We performed a systematic review and meta-analysis of 2 randomized clinical trials (RCT) and 7 non-randomized observational studies (nROS). Hazard ratios (HR) and 95% confidence intervals (CI) were pooled through inverse variance random-effects model to compute the summary effect size for all-cause death, cardiovascular death and cardiac-related hospitalization. Subgroup and meta-regression analysis were also performed.Results: An overall population of 3118 individuals (67% men; mean age, 73 years) was included: 1775 PMVR+OMT and 1343 OMT patients, with mean follow-up of 24 ± 15 months. PMVR+OMT was associated with a lower risk of all-cause death (HR: 0.77; 95% CI: 0.68-0.87), cardiovascular death (HR: 0.55; 95% CI: 0.34-0.89) and cardiac-related hospitalization (HR:0.77; 95% CI: 0.64-0.92). Meta-regression analysis showed that larger left ventricular end-diastolic volume index (LVEDVI) portends higher risk of all-cause death, cardiovascular death and cardiac-related hospitalization after PMVR (p < 0.001 for all).Conclusions: This study-level meta-analysis shows that PMVR+OMT is associated with reduced all-cause death, cardiovascular death and cardiac-related hospitalization when compared with OMT alone in secondary MR. LVEDVI is a predictive marker of efficacy, as patients with smaller LVEDVI have been shown to derive the largest benefit from PMVR. [ABSTRACT FROM AUTHOR]

Abstract Background The optimal treatment of patients undergoing percutaneous coronary interventions (PCI) for lesions located at coronary bifurcations is still debated. Methods Data on 5036 consecutive patients who underwent PCI on coronary bifurcation at 17 major coronary intervention centers between January 2012 and December 2014 were collected. Results Follow-up at a median 18 months (IQR 11-28) was available for 4506 patients (89%). Major Adverse Cardiac Events (MACE) occurred in 395 patients (8.8%): cardiac death in 152 (3.4%), myocardial infarction, excluding periprocedural, in 156 (3.5%) and stent thrombosis in 110 cases (2.4%). At multivariable Cox regression, left ventricular ejection fraction ≤30% (P < 0.001), bail-out stenting (beyond a planned strategy of either single or double stenting) (P < 0.001), admission for an acute coronary syndrome (P < 0.001), age >66 years (P < 0.001), multivessel disease (P < 0.001) and diabetes (P < 0.001) were independently associated with MACE. Sensitivity analysis identified premature discontinuation of dual antiplatelet therapy (DAPT) (P < 0.001) and side branch (SB) lesion length ≥9 mm (P < 0.05) as additional independent predictors of MACE. Conclusions Beyond traditional risk factors, multivessel disease, the length of the SB lesion, "bail-out" stenting and premature DAPT discontinuation are independent predictors of mid-term MACE after PCI of coronary bifurcations. This highlights the importance of a carefully planned PCI strategy and adequate therapy adherence to improve the clinical outcomes in these patients. Clinical trial registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT01967615. Highlights • In PCI on coronary bifurcations age, diabetes, ACS and reduced LVEF are clinical variables independently associated with MACE. • Among angiographic variables, multivessel CAD and the SB lesion length, not Medina, are independent predictors of MACE. • In the treatment strategy, a "bail-out" placement of stent beyond planning is independently associated with adverse events. • Discontinuation from DAPT <6 months in patients with SCAD and <12 months with after an ACS is an independent predictor of MACE. [ABSTRACT FROM AUTHOR]

Although the treatment of acute coronary syndromes (ACS) has advanced considerably, the ability to detect, predict, and prevent complications of atherosclerotic plaques, considered the main cause of ACS, remains elusive. Several imaging tools have therefore been developed to characterize morphological determinants of plaque vulnerability, defined as the propensity or probability of plaques to complicate with coronary thrombosis, able to predict patients at risk. By utilizing both intravascular and noninvasive imaging tools, indeed prospective longitudinal studies have recently provided considerable knowledge, increasing our understanding of determinants of plaque formation, progression, and instabilization. In the present review we aim at 1) critically analyzing the incremental utility of imaging tools over currently available “traditional” methods of risk stratification; 2) documenting the capacity of such modalities to monitor atherosclerosis progression and regression according to lifestyle modifications and targeted therapy; and 3) evaluating the potential clinical relevance of advanced imaging, testing whether detection of such lesions may guide therapeutic decisions and changes in treatment strategy. The current understanding of modes of progression of atherosclerotic vascular disease and the appropriate use of available diagnostic tools may already now gauge the selection of patients to be enrolled in primary and secondary prevention studies. Appropriate trials should now, however, evaluate the cost-effectiveness of an aggressive search of vulnerable plaques, favoring implementation of such diagnostic tools in daily practice. [ABSTRACT FROM AUTHOR]

Coronary collaterals are present at birth, with wide interindividual variation in their functional capacity. These vessels protect jeopardized myocardium, and the number of collaterals and the extent of their coverage are associated with improved survival in patients with coronary heart disease. The collateral circulation is not a permanent set of structures, but undergoes dynamic changes with important consequences for cardioprotection. If a severe atherosclerotic lesion develops in an artery supplying tissue downstream of a total occlusion through collateral blood flow, pressure gradients across the collateral bed change. The result is that some of the collateral flow previously supplying the perfusion territory of the totally occluded artery is redirected to the perfusion territory of the donor artery, thus producing a 'collateral steal'. The collateral circulation can regress once antegrade flow in the main dependent artery is re-established, as occurs following the recanalization of a chronic total occlusion. The clinical benefits of coronary revascularization must be cautiously weighed against the risk of reducing the protective support derived from coronary collaterals. Consequently, pharmacological, gene-based, and cell-based therapeutic attempts have been made to enhance collateral function. Although such approaches have so far yielded no, or modest, beneficial results, the rapidly accruing data on coronary collateral circulation will hopefully lead to new effective therapeutic strategies. [ABSTRACT FROM AUTHOR]

Abstract: In patients with multi-vessel coronary artery disease (MVCAD) myocardial revascularization may be accomplished either on all diseased lesions – complete myocardial revascularization – or on selectively targeted coronary segments by percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). Complete revascularization has a potential long-term prognostic benefit, but is more complex and may increase in-hospital events when compared with incomplete revascularization. No conclusive agreement has been yet reached on the “optimal” extent of revascularization, and guidelines have only recently mentioned the adequacy of revascularization in the decision whether to submit a patient to CABG or PCI. In the absence of any trial specifically designed to assess the relative benefit of either strategy, the present review explores current concepts about the completeness of revascularization, the growing evidence on the relevance of lesion and myocardial functional evaluation, and analyzes currently available data in relation to different clinical settings, including acute coronary syndromes, diabetes, chronic kidney disease and impaired left ventricular function. Considerations on the adequacy of revascularization should guide the choice among PCI and CABG in patients with MVCAD during the decision-making process, taking into account the clinical presentation, the extent and relevance of ischemia and the presence of other comorbidities. [Copyright &y& Elsevier]

Background: Because ST segment depression has limited diagnostic performance at exercise electrocardiography (ECG), ST segment depression/heart rate (ST/HR) hysteresis and cardiopulmonary exercise test (CPET)-derived parameters have been proposed as alternatives to diagnose exercise-induced myocardial ischemia. We compared the diagnostic performance of such parameters. Methods: We studied 56 subjects (45 men, 11 women, age 59.7±13.6years) referred for suspected exercise-induced myocardial ischemia with an equivocal ECG exercise test. All subjects serially underwent CPET and a myocardial single-photon emission computerized tomography (SPECT) perfusion imaging (as the gold standard for ischemia). Maximum ST depression at peak exercise (ST-max), the ST/HR hysteresis, ΔVO2/ΔWR b–b1 slope, ΔVO2/ΔWR (aa1–bb1), VO2/HR flattening duration and other CPET parameters were derived in all subjects. Results: On the basis of SPECT, 23 subjects (41%) were considered ischemic and 33 subjects (59%) non-ischemic. ST/HR hysteresis was higher (0.026mV; 95% CI: 0.003 to 0.049 vs −0.016mV; 95% CI: −0.031 to −0.001mV) and ST-max was lower (−0.105mV; 95% CI: −0.158 to −0.052 vs 0.032mV; 95% CI: −0.001 to −0.066mV) in ischemic vs non-ischemic subjects (P=0.004 and P=0.001, respectively). Among CPET parameters, ΔVO2/ΔWR b–b1 slope was lower (9.4±3.8) and ΔVO2/ΔWR (aa1–bb1) was higher (2.1±2.6) in ischemic vs non-ischemic subjects (11.4±2.3, P=0.005, and 1.1±1.5, P=0.001, respectively). The ST/HR hysteresis had the highest area under the curve value, better (P<0.05) than any other parameters tested, thus showing the highest overall diagnostic performance. Conclusion: The ST/HR hysteresis is superior to CPET-derived parameters for detecting exercise-induced myocardial ischemia in patients with equivocal ECG exercise test results. [ABSTRACT FROM AUTHOR]

Abstract: An increase of biomarkers of myocardial necrosis is observed frequently after percutaneous coronary interventions (PCI) even when the procedure seems angiographically successful and otherwise uncomplicated. The recently updated Universal Definition of Myocardial infarction (MI) arbitrarily defined periprocedural MI (type 4a) by elevation of cardiac troponin (cTn) values >5 × the upper reference limit (URL) in patients with normal baseline values or a rise of cTn values >20% if the baseline values are elevated, together with either angina or new ECG changes or angiographic loss of patency of a coronary artery or a side branch or persistent slow or no-flow or embolization, or imaging demonstration of new loss of viable myocardium. Most frequent causes of such event are side-branch closure and/or plaque microembolization. The present review is focused on the prognostic implication of periprocedural necrosis. The risk related to a PCI-induced MI is significantly lower as compared to a spontaneous event where a similar increase of biomarkers is detected. Moreover, although an association between CK-MB elevations and adverse prognosis after PCI has been documented, existing data do not support the statement that an isolated elevation of troponins after PCI is associated with an adverse prognosis after PCI; increased troponin levels before PCI seem far more predictive of future events than a peri-procedural itself. Caution should be paid in the interpretation of clinical trials using type 4a MI as a primary endpoint. Nevertheless, patients with periprocedural myocardial damage should be treated as a higher-risk cohort, carefully monitored and receive an intensified secondary prevention program. [Copyright &y& Elsevier]

Abstract: Mechanical debulking of coronary plaques with rotational atherectomy (RA) has been used for more than 20years during percutaneous coronary interventions (PCI). Modification of plaque characteristics may be accomplished with selective ablation of inelastic fibrocalcific tissue. The use of RA, though reduced with the development of bare-metal stents (BMS) and even more with drug-eluting stents (DES), has never been completely abandoned. The present review will analyze reasons for conflicting results obtained in large series and randomized trials on this topic in the past, and will identify criteria for an appropriate use in current times. [Copyright &y& Elsevier]

Abstract: Percutaneous coronary intervention (PCI) is often “associated” with myocardial injury. This event has been considered in the past as an acceptable trade-off for an optimal stent deployment. More recently, in the Universal Definition of myocardial infarction (MI), an increase of either cardiac troponins or creatine kinase-MB >3 times the upper reference limit (URL) has been defined as MI. Although there is no doubt on the accuracy of cardiac troponins in the diagnosis of spontaneous MI, existing data do not support the hypothesis that an isolated elevation of cardiac troponins over such threshold is associated with an adverse prognosis after PCI. [Copyright &y& Elsevier]

A letter to the editor is presented in response to the article "A Prospective Natural-History Study of Coronary Atherosclerosis," by G. W. Stone, A. Maehara, A. J. Lansky et al in the January 20, 2011 issue.

Background It has been suggested that corrected QT dispersion (cQTD) provides a measure of repolarisation inhomogeneity; however, the existence of a relationship between cQTD and cardiac outcomes is controversial. Objective To assess whether changes in cQTD following percutaneous coronary intervention (PCI) predict long-term survival. Design Prospective observational study. Setting Single tertiary care centre. Main outcome measures Cardiac mortality. Patients 612 patients had a 12-lead ECG recorded before and 6 h after PCI, and were followed-up for 49±10 months. Results PCI was associated with a significant overall reduction of cQTD at 6 h versus baseline (p<0.001); a reduction in cQTD occurred in 343 patients (56%). During the follow-up, 46 deaths (7.5%) were recorded, 21 of which for non-cardiac and 25 for cardiac causes. At Cox regression analysis, a reduced DcQTD (cQTD baseline -6 h) was an independent predictor of cardiac mortality (HR=1.497; 95% CI 1.081 to 2.075 for each 20 ms decrease; p=0.015), together with age (HR=1.672; 95% CI 1.039 to 2.691 per 10 years increase; p=0.034), diabetes (HR=2.622; 95% CI 1.112 to 6.184; p=0.028), peak CK-MB (HR=1.798; 95% CI 1.063 to 3.039 per each unit increase over normal level; p=0.029), three-vessel coronary artery disease (HR=3.626; 95% CI 1.079 to 12.187; p=0.037) and the number of treated lesions (HR=2.066; 95% CI 1.208 to 3.532; p=0.008). Patients in the lowest tertile of DcQTD and having a post-procedural increase of CK-MB had a considerably higher cardiac mortality than the remaining population (14.6 vs 2.4%, p<0.001). Conclusions cQTD decreases after PCI. A defective cQTD recovery, suggesting the persistence of repolarisation inhomogeneities, predicts long-term cardiac mortality. [ABSTRACT FROM AUTHOR]

Abstract: Objective: We tested the ability of optical coherence tomography (OCT) to identify very early stages of atherosclerosis in vivo. Methods: Twelve New Zealand white male rabbits (weight 3.5–4.0kg) underwent perivascular electrical injury of the common carotid arteries, and were then fed a cholesterol-rich diet. At 43±16 (range 27–63) days after injury, arteries were imaged by OCT, then rabbits were euthanized and vessels processed for histology. Results: A total of 14 carotid arteries were imaged by OCT and histology; 22 atherosclerotic lesions were identified, 16 (73%) occurring at the site of the electrical injury. At histology, 4 lesions were defined as Stary type I (isolated macrophages), 8 as type II (intracellular lipid accumulations), and 10 as type III (small extracellular lipid pools). No advanced (≥type IV) lesions were documented. OCT failed to detect any type I lesions, but correctly defined a minority (2/8, 25%) of type II lesions and the majority (8/10, 80%) of type III lesions. For type III lesions, sensitivity, specificity and diagnostic accuracy of OCT were 80%, 95%, and 95%, respectively. Conclusions: OCT can accurately detect intermediate (type-III) atherosclerotic lesions in vivo, but still fails to identify earlier stages of atherosclerosis. [Copyright &y& Elsevier]

Objectives: We evaluated the time-behavior of changes in collateral circulation after successful percutaneous coronary intervention (PCI) with drug-eluting stents (DES) in chronic (>1 month) total occlusions (CTO), and assessed their relationship with myocardial ischemia. Background: It has been hypothesized that the immediate reduction of collateral flow after PCI of CTO could expose the patients to a higher risk of future ischemic events in the case of vessel reocclusion. Methods: In 42 patients with CTO, two consecutive balloon inflations and final DES deployment were performed after positioning of a pressure guidewire. Minimal lumen diameter (MLD), diameter stenosis (DS), angiographic collateral grading (Rentrop score), myocardial (FFRmyo), coronary (FFRcor), and collateral fractional flow reserve (FFRcoll) were evaluated. Chest pain and the sum of ST-segment elevation (ΣST) were analyzed to document the occurrence and extent of myocardial ischemia. Results: Percutaneous coronary intervention induced a progressive improvement of indexes of stenosis severity (MLD, DS, Thrombolysis in Myocardial Infarction flow, FFRmyo, and FFRcor) and a rapid reduction in collateral circulation (FFRcoll and Rentrop score). A progressive worsening of ischemia at each balloon inflation occurred, concomitant with the reduction of collateral circulation. At linear regression analysis, an inverse relationship of FFRcoll with ΣST (R2 = 0.352, p < 0.001) and angina pain score (R2 = 0.247, p < 0.001) was observed. Conclusions: In CTO, collateral circulation, which provides most coronary flow at baseline, rapidly declines after successful stent implantation and the restoration of an antegrade flow. This rapid de-recruitment of collaterals is likely to put such patients at risk of future ischemic events. [Copyright &y& Elsevier]

Four weeks’ therapy with clopidogrel, in addition to aspirin (acetylsalicylic acid), is currently standard care after percutaneous coronary intervention (PCI) with stent implantation. The recent availability of drug-eluting stents (DES), which dramatically reduce restenosis at the site of PCI, has again raised the issue of stent thrombosis. In clinical trials, the risk of stent thrombosis appeared unrelated to the presence of the drug eluting from the stent and was documented within the usual range of ≤1% at 9 months after DES implantation. However, these devices feature delayed strut endothelialisation and there are reports describing late DES thrombosis up to 18 months after PCI, in most cases after clopidogrel has been discontinued. Although infrequent after bare-metal stenting (0.4–2.8%), stent thrombosis is a catastrophic event. Before DES availability, adjunctive intravascular brachytherapy significantly reduced in-stent neointimal proliferation, at the price of a higher-than-expected rate of late stent occlusion (6–8%). In such setting, a 12-month aspirin plus clopidogrel regimen showed a beneficial effect on long-term adverse events. An additional consideration is that, among patients undergoing bare-metal stent PCI, combined antithrombotic therapy with aspirin and clopidogrel has been recently associated with favourable effects on cardiovascular outcome beyond stent thrombosis in two large-scale clinical trials. Therefore, we propose that prolonged combination therapy with aspirin and clopidogrel be mandatory up to 1 year after PCI in all patients receiving DES. [ABSTRACT FROM AUTHOR]

The high mortality in the global population due to chronic diseases highlights the urgency to identify effective alternative therapies. Regenerative medicine provides promising new approaches for this purpose, particularly in the use of induced pluripotent stem cells (iPSCs). The aim of the work is to establish a new pluripotency cell line obtained for the first time by reprogramming human gingival mesenchymal stem cells (hGMSCs) by a non-integrating method. The hGMSC-derived iPS line characterization is performed through morphological analysis with optical and electron scanning microscopy and through the pluripotency markers expression evaluation in cytofluorimetry, immunofluorescence, and RT-PCR. To confirm the pluripotency of new hGMSC-derived iPS, the formation of embryoid bodies (EBs), as an alternative to the teratoma formation test, is studied in morphological analysis and through three germ layers' markers' expression in immunofluorescence and RT-PCR. At the end, a comparative study between parental hGMSCs and derived iPS cells is performed also for the extracellular vesicles (EVs) and their miRNA content. The new hGMSC-derived iPS line demonstrated to be pluripotent in all aspects, thus representing an innovative dynamic platform for personalized tissue regeneration. [ABSTRACT FROM AUTHOR]

Introduction: The role of endothelial progenitor cells (EPCs) in atherosclerosis progression and neointimal growth after percutaneous coronary intervention (PCI) remains controversial. The purpose of this study was to perform a systematic review and meta-analysis of studies on EPCs in patients who had PCI.Methods: We searched Pubmed, Embase and Cochrane databases and reviewed cited references up to August 31, 2021. Overall, we selected 9 studies, including 4612 patients.Results: Lower baseline EPC count was associated with a significantly greater occurrence of in-stent restenosis (HR 1.33; 95% CI 0.97-1.82, P = 0.045). As for EPC coating, there was no significant difference in the 1-year occurrence of cardiac death between EPCs-capturing drug-eluting stents (DES) and standard DES (Relative Risk [RR] 1.146; 95% CI 0.666-1.974, P = 0.98), but target lesion revascularization (RR 1.727; 95% CI: 1.199-2.487, P = 0.025), and target vessel failure (RR 1.591; 95% CI 1.213-2.088, P = 0.04) were significantly more common with EPCs-capturing DES than with standard DES.Conclusion: Circulating EPC count might improve risk stratification after PCI, as it is correlated with the occurrence of in-stent restenosis. Currently available EPCs-capturing DES use was associated with an increased risk of 1-year adverse events, mainly driven by an increase in target lesion revascularization and target vessel failure, not cardiac death. [ABSTRACT FROM AUTHOR]

Angina pectoris may arise from obstructive coronary artery disease (CAD) or in the absence of significant CAD (ischemia with nonobstructed coronary arteries [INOCA]). Therapeutic strategies for patients with angina and obstructive CAD focus on reducing cardiovascular events and relieving symptoms, whereas in INOCA the focus shifts toward managing functional alterations of the coronary circulation. In obstructive CAD, coronary revascularization might improve angina status, although a significant percentage of patients present angina persistence or recurrence, suggesting the presence of functional mechanisms along with epicardial CAD. In patients with INOCA, performing a precise endotype diagnosis is crucial to allow a tailored therapy targeted toward the specific pathogenic mechanism. In this expert opinion paper, we review the evidence for the management of angina, highlighting the complementary role of coronary revascularization, optimal medical therapy, and lifestyle interventions and underscoring the importance of a personalized approach that targets the underlying pathobiology. • Angina pectoris may arise from obstructive CAD or in the absence of significant CAD. • Functional mechanisms may be involved in determining angina both in obstructive CAD and in ischemia with nonobstructed coronary arteries. • Revascularization and medical therapy play complementary roles in achieving optimal outcomes for patients with angina. • Management of angina is shifting toward a more personalized approach, moving away from the traditional one-size-fits-all strategy. [ABSTRACT FROM AUTHOR]

To assess the reproducibility of coronary tissue characterization by an Artificial Intelligence Optical Coherence Tomography software (OctPlus, Shanghai Pulse Medical Imaging Technology Inc.). 74 patients presenting with multivessel ST-segment elevation myocardial infarction (STEMI) underwent optical coherence tomography (OCT) of the infarct-related artery at the end of primary percutaneous coronary intervention (PPCI) and during staged PCI (SPCI) within 7 days thereafter in the MATRIX (Minimizing Adverse Hemorrhagic Events by Transradial Access Site and angioX) Treatment-Duration study (ClinicalTrials.gov , NCT01433627). OCT films were run through the OctPlus software. The same region of interest between either side of the stent and the first branch was identified on OCT films for each patient at PPCI and SPCI, thus generating 94 pairs of segments. 42 pairs of segments were re-analyzed for intra-software difference. Five plaque characteristics including cholesterol crystal, fibrous tissue, calcium, lipid, and macrophage content were analyzed for various parameters (span angle, thickness, and area). There was no statistically significant inter-catheter (between PPCI and SPCI) or intra-software difference in the mean values of all the parameters. Inter-catheter correlation for area was best seen for calcification [intraclass correlation coefficient (ICC) 0.86], followed by fibrous tissue (ICC 0.87), lipid (ICC 0.62), and macrophage (ICC 0.43). Some of the inter-catheter relative differences for area measurements were large: calcification 9.75 %; cholesterol crystal 74.10 %; fibrous tissue 5.90 %; lipid 4.66 %; and macrophage 1.23 %. By the intra-software measurements, there was an excellent correlation (ICC > 0.9) for all tissue types. The relative differences for area measurements were: calcification 0.64 %; cholesterol crystal 5.34 %; fibrous tissue 0.19 %; lipid 1.07 %; and macrophage 0.60 %. Features of vulnerable plaque, minimum fibrous cap thickness and lipid area showed acceptable reproducibility. The present study demonstrates an overall good reproducibility of tissue characterization by the Artificial Intelligence Optical Coherence Tomography software. In future longitudinal studies, investigators may use discretion in selecting the imaging endpoints and sample size, accounting for the observed relative differences in this study. • Inter-catheter and intra-software mean difference was statiscially insignificant for all the parameters analyzed by OCTplus. • Inter-catheter correlation for area was best seen for calcification (ICC 0.86), followed by fibrous tissue (ICC 0.87). • Excellent correlation (ICC > 0.9) for all tissue types was seen for intra-software measurements. • Given good inter-catheter and intra-software reproducibility, the software can be used in future longitudinal studies. [ABSTRACT FROM AUTHOR]

Background: Non-vitamin K oral anticoagulants (NOACs) are proven alternatives to vitamin K antagonists (VKAs) for the prevention of thromboembolism in patients with nonvalvular atrial fibrillation. However, there are few data on the efficacy and safety of NOAC therapy after cardioversion, where the risk of thromboembolic events is heightened.Methods: We performed a random-effects meta-analysis of patients who underwent both electrical and pharmacologic cardioversion for atrial fibrillation in the RE-LY, ROCKET-AF, ARISTOTLE, ENGAGE AF-TIMI 48, and X-VeRT trials. We assessed Mantel-Haenszel pooled estimates of risk ratio (RR) and 95% confidence intervals (CIs) for stroke/systemic embolism and major bleeding at ≤42 days of follow-up.Results: The analysis pooled 3949 patients in whom a total of 4900 cardioversions for atrial fibrillation were performed. Compared with VKAs, NOAC therapy was associated with a similar risk of stroke/systemic embolism (RR 0.84; 95% CI, 0.34-2.04) and major bleeding (RR 1.12; 95% CI, 0.52-2.42); no significant statistical heterogeneity was found among studies (Cochrane Q P = .59, I(2) = 0% for stroke/systemic embolism; P = .47; I(2) = 0% for major bleeding).Conclusions: The short-term incidences of thromboembolic and major hemorrhagic events after cardioversion on NOACs were low and comparable to those observed on dose-adjusted VKA therapy. Non-vitamin K oral anticoagulants are a reasonable alternative to VKAs in patients undergoing cardioversion. [ABSTRACT FROM AUTHOR]

Sarcomeric hypertrophic cardiomyopathy (HCM) is a prevalent genetic disorder characterised by left ventricular hypertrophy, myocardial disarray, and an increased risk of heart failure and sudden cardiac death. Despite advances in understanding its pathophysiology, treatment options for HCM remain limited. This narrative review aims to provide a comprehensive overview of current clinical practice and explore emerging therapeutic strategies for sarcomeric HCM, with a focus on cardiac myosin inhibitors. We first discuss the conventional management of HCM, including lifestyle modifications, pharmacological therapies, and invasive interventions, emphasizing their limitations and challenges. Next, we highlight recent advances in molecular genetics and their potential applications in refining HCM diagnosis, risk stratification, and treatment. We delve into emerging therapies, such as gene editing, RNA-based therapies, targeted small molecules, and cardiac myosin modulators like mavacamten and aficamten, which hold promise in modulating the underlying molecular mechanisms of HCM. Mavacamten and aficamten, selective modulators of cardiac myosin, have demonstrated encouraging results in clinical trials by reducing left ventricular outflow tract obstruction and improving symptoms in patients with obstructive HCM. We discuss their mechanisms of action, clinical trial outcomes, and potential implications for the future of HCM management. Furthermore, we examine the role of precision medicine in HCM management, exploring how individualised treatment strategies, including exercise prescription as part of the management plan, may optimise patient outcomes. Finally, we underscore the importance of multidisciplinary care and patient-centred approaches to address the complex needs of HCM patients. This review also aims to encourage further research and collaboration in the field of HCM, promoting the development of novel and more effective therapeutic strategies, such as cardiac myosin modulators, to hopefully improve the quality of life and outcome of patients with sarcomeric HCM. [ABSTRACT FROM AUTHOR]

To identify the best strategy to achieve complete revascularization (CR) in patients with ST-elevation myocardial infarction (STEMI) and multi-vessel disease (MVD). We systematically reviewed the literature for randomized controlled trials (RCTs) comparing IRA-only PCI and CR guided by angiography or fractional flow reserve (FFR) in MVD-STEMI. Both frequentist (classical) and Bayesian network meta-analysis were performed, including a comparative hierarchy estimation of the probability to reduce the primary composite endpoint of all-cause death and new myocardial infarction (MI). We identified 11 RCTs, including 8193 STEMI patients. Compared with IRA-only strategy, CR significantly reduced the primary endpoint (OR: 0.73; 95%CI0.55–0.97). We observed non-significant difference between angiography and FFR guidance in reducing the primary endpoint (OR: 0.73, 95% CI 0.35–1.57). The Bayesian probability analysis ranked angio-guided CR as the best intervention yielding lowest risk of all-cause death or new MI (SUCRA92%). In patients with MVD-STEMI, CR is associated with a reduction in all-cause mortality and new MI compared with IRA-only PCI. Angio-guided CR is associated with the lowest risk of all-cause death or new MI, therefore the role of FFR-guidance in this setting is questionable. Both frequentist and Bayesian network meta-analysis were performed to compare infarct-related artery (IRA)-only percutaneous coronary intervention (PCI) and complete revascularization (CR) guided by angiography or fractional flow reserve (FFR) in multivessel disease (MVD) and acute ST-elevation myocardial infarction (STEMI). Eleven randomized controlled trials were identified, including 8193 STEMI patients. Compared with IRA-only strategy, CR significantly reduced the incidence of the composite endpoint of all-cause death and new myocardial infarction without significant difference in angio-guided and FFR-guided CR. The Bayesian probability analysis ranked angio-guided CR as the best intervention yielding lowest risk of the composite endpoint and, therefore the role of FFR-guidance in this setting is questionable. • A meta-analysis of 11 trials compared angio-guided vs FFR-guided revascularization in STEMI. • Complete revascularization significantly reduced the incidence of all-cause death and new myocardial infarction • The Bayesian probability analysis ranked angio-guided CR as the best intervention yielding lowest risk [ABSTRACT FROM AUTHOR]

• Coronary microvascular disease is one of the most recognized causes of myocardial infarction in the absence of obstructive coronary artery disease (MINOCA), but assessment of coronary microvascular (dys)function is challenging. • Index of microcirculatory resistance (IMR) is a guidewire-based measurement that allows direct quantitative assessment of coronary microcirculation but has practical restrictions for AMI patients. • Angiography-derived IMR (caIMR), based on application of computational flow dynamics to three-dimensional modeling of the coronary artery, allows simple, offline, and guidewire-free microcirculatory assessment. • caIMR in MINOCA patients independently predicts major cardiovascular events at intermediate-term follow-up. [ABSTRACT FROM AUTHOR]

The widely observed between-subject variability in cognitive responses to coffee may have a genetic basis. We evaluated cognitive responses to caffeine throughout three complex cognitive tasks assessing different subdomains of attention, namely Alerting and Orienting (Categorical Search Task) and Executive Control (Stroop Task and Eriksen Flanker Task). We explored whether they are influenced by gene variants affecting adenosine metabolism or catecholamine receptors. We recruited 106 healthy male subjects who were administered, in a double-blind design, 40 mL of either a decaffeinated coffee preparation plus 3 mg/kg caffeine (caf) or the corresponding vehicle (decaf). The protocol was repeated 24 h later with the alternative preparation. Cognitive tasks were performed between 30 min and 2 h after caf or decaf administration. Each subject underwent ambulatory blood pressure monitoring for 2 h. Blood samples were collected for genetic evaluations and for plasma caffeine and catecholamines measures. We found a significant reduction of reaction times in two of the cognitive tasks (Categorical Search Task and Stroop Task) after caf compared with decaf, indicating that caffeine, on average, improved the attention level in the domains under investigation. We also found, however, a great inter-individual variability in the cognitive performance responses to caffeine. In exploring genetic sources for such variability, we found a relation between polymorphisms of adenosine A2A and the caffeine effects on the attentional domains of Orienting and Executive control. In conclusion, variability in the attentional response to coffee may be partly explained by genetic polymorphisms of adenosine and adrenergic receptors. [ABSTRACT FROM AUTHOR]

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor in patients undergoing percutaneous coronary intervention (PCI) reduces the risk of ischemic events but reduces the risk of ischemic events but increases the risk of bleeding, which in turn is associated with increased morbidity and mortality. With the aim to offer personalized treatment regimens to patients undergoing PCI, much effort has been devoted in the last decade to improve the identification of patients at increased risk of bleeding complications. Several clinical scores have been developed and validated in large populations of patients with coronary artery disease (CAD) and are currently recommended by guidelines to evaluate bleeding risk and individualize the type and duration of antithrombotic therapy after PCI. In clinical practice, these risk scores are conventionally computed at the time of PCI using baseline features and risk factors. Yet, bleeding risk is dynamic and can change over time after PCI, since patients can worsen or improve their clinical status and accumulate comorbidities. Indeed, evidence now exists that the estimated risk of bleeding after PCI can change over time. This concept is relevant, as the inappropriate estimation of bleeding risk, either at the time of revascularization or subsequent follow-up visits, might lead to erroneous therapeutic management. Serial evaluation and recalculation of bleeding risk scores during follow-up can be important in clinical practice to improve the identification of patients at higher risk of bleeding while on DAPT after PCI. [ABSTRACT FROM AUTHOR]

Background and objectives: The absence of obstructive coronary artery disease (CAD) in patients with angina is common, but its prognosis is debated. We investigated outcomes of such patients to identify predictors of cardiovascular events. Methods: We selected 1014 patients with angina, evidence of myocardial ischemia at the electrocardiogram (ECG) exercise test or imaging stress tests, and nonobstructive CAD (absence of lumen diameter reduction ≥50%) at coronary angiography between 1999 and 2015. Note that, 1905 age‐ and risk factors‐matched asymptomatic subjects served as "real‐world" comparators. The primary endpoint was the occurrence of all‐cause death or myocardial infarction. Results: At 6‐years median follow‐up (interquartile range, 3–9 years), the primary endpoint occurred in 53 patients (5.5%, 0.92/100 person‐years). Besides similar event rates compared with asymptomatic subjects (hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.62–1.15, p = 0.28), the index population showed a very heterogeneous prognosis. Patients with nonobstructive CAD (HR 1.85, 95% CI 1.02–3.37, p = 0.04, compared with "normal" coronary arteries) and ischemia at imaging tests (HR 2.11, 95% CI 1.07–4.14, p = 0.03, compared with ischemia detected only at the ECG exercise test) were at higher risk and those with both these components showing even >10‐fold event rates as compared with the absence of both. Three‐hundred and twenty‐five patients (34%) continued to experience angina, 69 (7.2%) underwent repeat coronary angiography, and 14 (1.5%) had consequent coronary revascularization for atherosclerosis progression. Conclusion: Apart from the impaired quality of life, angina without obstructive CAD has an overall benign but very heterogeneous prognosis. Nonobstructive CAD and myocardial ischemia at imaging tests both confer a higher risk. [ABSTRACT FROM AUTHOR]

In-stent restenosis (ISR) is a major limitation of coronary stenting and is associated with high recurrence rates after intervention with all available devices. Intracoronary gamma (γ) radiation was proved to reduce the recurrence rate after conventional therapy. The purpose of this study was to compare the different devices utilized for the treatment of ISR with and without γ radiation. To search for the optimal device for the treatment of ISR, 685 patients from the radiation trials for ISR who were randomized to either iridium-192 γ radiation (559 patients) or placebo (126 patients) following intervention were evaluated. Devices used included balloon percutaneous transluminal coronary angioplasty, excimer laser coronary angioplasty (ELCA), rotational atherectomy, and additional stent implantation. Baseline clinical and angiographic characteristics were similar between the γ radiation and placebo groups. One- and 6-month clinical and angiographic outcomes were compared. The use of stenting compared with other devices was associated with increased late loss. Device selection used as adjunctive therapy did not influence the 30-day outcome. Patients treated with γ radiation and placebo therapy had similar rates of composite major adverse coronary events (MACE) (death, Q-wave myocardial infarction, target vessel revascularization) (3% vs 2%, p = NS). At 6 months, MACE rates in irradiated patients were similar among POBA (29%), ELCA (28%), rotational atherectomy (18%), and additional stent implantation (30%, p = NS), and were significantly lower compared with placebo for the entire cohort and for each device subgroup. The overall recurrence rate of ISR was lower in patients treated with γ radiation using iridium-192 compared with placebo. Device selection did not influence late clinical outcomes in irradiated and nonirradiated groups. [Copyright &y& Elsevier]

Contemporary evidence supports device-based transcatheter interventions for the management of patients with structural heart disease. These procedures, which include aortic valve implantation, mitral or tricuspid valve repair/implantation, left atrial appendage occlusion, and patent foramen ovale closure, profoundly differ with respect to clinical indications and procedural aspects. Yet, patients undergoing transcatheter cardiac interventions require antithrombotic therapy before, during, or after the procedure to prevent thromboembolic events. However, these therapies are associated with an increased risk of bleeding complications. To date, challenges and controversies exist regarding balancing the risk of thrombotic and bleeding complications in these patients such that the optimal antithrombotic regimens to adopt in each specific procedure is still unclear. In this review, we summarize current evidence on antithrombotic therapies for device-based transcatheter interventions targeting structural heart disease and emphasize the importance of a tailored approach in these patients. [ABSTRACT FROM AUTHOR]

Pulmonary embolism (PE) is a potentially life-threatening condition that remains a major global health concern. Noteworthy, patients with high- and intermediate-high-risk PE pose unique challenges because they often display clinical and hemodynamic instability, thus requiring rapid intervention to mitigate the risk of clinical deterioration and death. Importantly, recovery from PE is associated with long-term complications such as recurrences, bleeding with oral anticoagulant treatment, pulmonary hypertension, and psychological distress. Several novel strategies to improve risk factor characterization and management of patients with PE have recently been introduced. Accordingly, this position paper of the Working Group of Interventional Cardiology of the Italian Society of Cardiology deals with the landscape of high- and intermediate-high risk PE, with a focus on bridging the gap between the evolving standards of care and the current clinical practice. Specifically, the growing importance of catheter-directed therapies as part of the therapeutic armamentarium is highlighted. These interventions have been shown to be effective strategies in unstable patients since they offer, as compared with thrombolysis, faster and more effective restoration of hemodynamic stability with a consistent reduction in the risk of bleeding. Evolving standards of care underscore the need for continuous re-assessment of patient risk stratification. To this end, a multidisciplinary approach is paramount in refining selection criteria to deliver the most effective treatment to patients with unstable hemodynamics. In conclusion, the current management of unstable patients with PE should prioritize tailored treatment in a patient-oriented approach in which transcatheter therapies play a central role. [Display omitted] • Patients with high- and intermediate-high-risk pulmonary embolism display clinical and hemodynamic instability requiring rapid intervention. • This position paper highlights catheter-directed therapies as part of the therapeutic armamentarium. • Continuous multidisciplinary risk stratification is paramount in refining selection criteria to deliver the most effective treatment. • Management of unstable patients should prioritize a patient-oriented treatment in which transcatheter therapies play a central role. [ABSTRACT FROM AUTHOR]

Objectives: We tested the noninferiority of a fast-track rule-out protocol for the diagnosis of non-ST-segment elevation myocardial infarction vs noncoronary chest pain based on the single-sampling combined assessment of medium-sensitivity cardiac troponin I and ultra-sensitive copeptin compared with the serial assessment of medium-sensitivity cardiac troponin I.Methods: Ultra-sensitive copeptin and medium-sensitivity cardiac troponin I levels were measured at presentation in 196 consecutive patients admitted to the emergency department for acute nontraumatic chest pain within 6 hours from symptoms onset and without ST-segment elevation on a 12-lead electrocardiogram. The diagnostic performance for non-ST-segment elevation myocardial infarction diagnosis of the dual-marker single-sampling strategy with medium-sensitivity cardiac troponin I and ultra-sensitive copeptin on admission was compared with that of the serial 0- and 3-hour medium-sensitivity cardiac troponin I sampling in reference to the adjudicated postdischarge diagnosis, using both the comparison of area under the curve (AUC) receiver operating characteristic and the McNemar chi-square test.Results: The diagnosis of non-ST-segment elevation myocardial infarction was adjudicated in 29 patients (14.8%). The combination of medium-sensitivity cardiac troponin I and ultra-sensitive copeptin generated an AUC of 0.87 (95% confidence interval, 0.82-0.91), which was noninferior with respect to the 3-hour interval medium-sensitivity cardiac troponin I serial sampling (P = .194 for AUC difference). The combination of medium-sensitivity cardiac troponin I and ultra-sensitive copeptin also yielded a numerically higher diagnostic sensitivity (100% vs 89.7%; P = not significant).Conclusions: A single-sampling strategy of combined ultra-sensitive copeptin and medium-sensitivity cardiac troponin I is noninferior to a 0- and 3-hour serial medium-sensitivity cardiac troponin I sampling in ruling out non-ST-segment elevation myocardial infarction and thus may allow an earlier discharge of patients who are ruled out for non-ST-segment elevation myocardial infarction (ClinicalTrials.gov Identifier NCT01962506). [ABSTRACT FROM AUTHOR]

Stent thrombosis (ST) is an infrequent (0.5% to 1.5%) complication of intracoronary stenting, with severe clinical consequences. This multicenter, randomized study evaluated the clinical outcome in 479 patients (598 lesions treated) who underwent elective coronary stenting with a Carbofilm-coated stent (CarboStent) who met prespecified eligibility criteria and were randomly assigned to receive aspirin alone (n = 235) or aspirin plus a thienopyridine antiplatelet regimen (n = 244). Clinical, angiographic, and procedural characteristics were similar between groups. The primary end point was the incidence of 30-day ST; secondary end points included major vascular or bleeding complications within 30 days and death, acute myocardial infarction, and target vessel revascularization at 6 months. ST occurred in 4 patients (1.4%) in the aspirin-only group and in 1 patient (0.3%) in the aspirin-plus-thienopyridine group (relative risk 0.23, 95% confidence interval 0.03 to 2.08, p = NS). After careful review of cases, 89 patients (19%) with protocol deviations were identified. When they were excluded from the analysis, no ST was observed in either group. Secondary end points were reached by 4% of the aspirin-alone group and 8% of the aspirin-plus-thienopyridine group (relative risk 2.35, 95% confidence interval 0.94 to 5.85, p = NS). In conclusion, after optimal intracoronary implantation of the CarboStent, antiplatelet therapy with aspirin alone was safe and provided efficacy comparable to aspirin plus a thienopyridine in the prevention of ST. [Copyright &y& Elsevier]