Search

Background: Optical coherence tomography (OCT) allows to carefully characterize coronary plaque morphology and lumen dimensions. We sought to evaluate the value of OCT in predicting fractional flow reserve (FFR). Methods: We performed a multicenter, international, pooled analysis of individual patient-level data from published studies assessing FFR and OCT on the same vessel. Data from stable or unstable patients who underwent both FFR and OCT of the same coronary artery were collected through a dedicated database. Predefined OCT parameters were minimum lumen area (MLA), percentage area stenosis (%AS), and presence of thrombus or plaque rupture. Primary end point was FFR ≤0.80. Secondary outcome was the incidence of major adverse cardiac events in patients not undergoing revascularization based on negative FFR (>0.80). Results: A total of 502 coronary lesions in 489 patients were included. A significant correlation was observed between OCT-MLA and FFR values (R = 0.525; P < .001), and between OCT-%AS and FFR values (R = –0.482; P < .001). In Receiver operating characteristic analysis, MLA <2.0 mm2 showed a good discriminative power to predict an FFR ≤0.80 (AUC, 0.80), whereas %AS >73% showed a moderate discriminative power (AUC, 0.73). When considering proximal coronary segments, the best OCT cutoff values predicting an FFR ≤0.80 were MLA <3.1 mm2 (AUC, 0.82), and %AS >61% (AUC, 0.84). In patients with a negative FFR not revascularized, the combination of lower MLA and higher %AS had a trend toward worse outcome (which was statistically significant in the analysis restricted to proximal vessels). Conclusions: OCT lumen measures (MLA, %AS) may predict FFR, and different cutoffs are needed for proximal vessels.

N/A

Refractory cardiogenic shock (RCS) or refractory cardiac arrest (RCA) complicating acute coronary syndrome (ACS) is associated with extremely high mortality rate. Veno-arterial extracorporeal life support (VA-ECLS) represents a valuable therapeutic option to stabilize patients’ condition before or at the time of emergency revascularization. We analyzed 29 consecutive patients with RCS or RCA complicating ACS, and implanted with VA-ECLS in two centers who have adopted a similar, structured approach to ECLS implantation. Data were collected from January 2010 to December 2015 and ECLS had to be percutaneously implanted either before (within 48 h) or at the time of attempted percutaneous coronary revascularization (PCI). We investigated in-hospital outcome and factors associated with survival. Twenty-one (72%) were implanted for RCA, whereas 8 (28%) were implanted on ECLS for RCS. All RCA were witnessed and no-flow time was shorter than 5 min in all cases but one. All patients underwent attempted emergency PCI, using radial access in ten cases (34.5%), whereas in three patients a subsequent CABG was performed. Overall, ten patients (34.5%) survived, nine of them with a good neurological outcome. Life threatening complications, including stroke (4 pts), leg ischemia (4 pts), intestinal ischemia (5 pts), and deep vein thrombosis 2 pts), occurred frequently, but were not associated with in-hospital death. Main cause of death was multi-organ failure. PCI variables did not predict survival. Survivors were younger, with shorter low-flow time, and with ECLS mainly implanted for RCS. At multivariate analysis, levels of lactate at ECLS implantation (OR 4.32, 95%CI 1.01–18.51, p = 0.049) emerged as the only variable that independently predicted survival. In patients with RCA or RCS complicating ACS who are percutaneously implanted with ECLS before or at the time of coronary revascularization, in hospital survival rate is higher than 30%. Level of lactate at ECLS im

Background: Contrast fractional flow reserve (cFFR) is a relatively new tool for the assessment of intermediate coronary artery stenosis and represents a reliable surrogate of FFR with the advantage of potentially simplifying functional evaluation. We aimed to compare the incidence of major adverse cardiac events (MACE) in patients undergoing functional evaluation with both FFR and cFFR based on the results of the two indexes. Method and Result: We retrospectively analyzed outcomes in 488 patients who underwent functional evaluation with FFR and cFFR. Patients were divided into four groups using the cutoff values of 0.80 for FFR and 0.85 for cFFR: −/− (n = 298), +/+ (n = 134), −/+(n = 31) and +/− (n = 25). All patients were treated according to FFR value. MACE rate was assessed in each group, including death, myocardial infarction and urgent target vessel revascularization (TVR). Mean follow-up time was 22 ± 15 months. Incidence of MACE at follow-up was 8.3% in FFR−/cFFR−, 14.0% in FFR+/cFFR+, 16.0% in FFR−/cFFR+ and 8.0% in FFR+/cFFR− without a significant difference amongst the 4 groups (p = 0.2). Nevertheless, a significant difference in the rate of TVR comparing FFR−/cFFR− (n = 17) and FFR−/cFFR+ (n = 5) was found at 24 months (5.7% vs 16.0%; p = 0.027). Conclusion: cFFR is accurate in predicting FFR and consequently reliable in guiding coronary revascularization. In the rare case of discordance, while FFR+/cFFR- patients show a prognosis similar to FFR-/cFFR- patients, FFR-/cFFR+ patients show a prognosis similar to FFR+/cFFR+ patients.

Despite the recent innovations in cardiovascular care, atherothrombosis is still a major complication of acute coronary syndromes (ACS). We evaluated the involvement of the CD31 molecule in thrombotic risk through the formation of monocyte-platelet (Mo-Plt) aggregates in patients with ACS with no-ST-segment elevation myocardial infarction (NSTEMI) on top of dual anti-platelet therapy (DAPT). We enrolled 19 control (CTRL) subjects, 46 stable angina (SA), and 86 patients with NSTEMI, of which, 16 with Intact Fibrous Cap (IFC) and 19 with Ruptured Fibrous Cap (RFC) as assessed by the Optical Coherence Tomography (OCT). The expression of CD31 on monocytes and platelets was measured. Following the coronary angiography, 52 NSTEMIs were further stratified according to thrombus grade (TG) evaluation. Finally, a series of ex vivo experiments verified whether the CD31 participates in Mo-Plt aggregate formation. In patients with NSTEMI, CD31 was reduced on monocytes and was increased on platelets, especially in NSTEMI presented with RFC plaques compared to those with IFC lesions, and in patients with high TG compared to those with zero/low TG. Ex vivo experiments documented an increase in Mo-Plt aggregates among NSTEMI, which significantly decreased after the CD31 ligation, particularly in patients with RFC plaques. In NSTEMI, CD31 participates in Mo-Plt aggregate formation in spite of optimal therapy and DAPT, suggesting the existence of alternative thrombotic pathways, as predominantly displayed in patients with RFC.

Left main (LM) coronary artery disease is a pathological condition of great clinical relevance due to its significant impact on both morbidity and mortality of patients with ischemic heart disease. An accurate assessment of the extent and characteristics of LM disease is often challenging due to the two-dimensional nature of angiography. For this reason, adjunctive techniques (i.e., intravascular imaging/functional assessment) have been introduced to aid the evaluation of LM disease severity and to guide invasive treatment. While intravascular ultrasound is still considered the invasive imaging modality of choice for the evaluation of ostial LM stenosis, optical coherence tomography (OCT) imaging, thanks to its unprecedented spatial resolution, is emerging as a valid alternative, in particular for the assessment of mid-shaft and distal LM stenosis. OCT imaging can be useful in each step of LM procedures: (1) to assess stenosis severity and to evaluate the need for revascularization; (2) to select the appropriate treatment strategy of LM bifurcation (e.g., single vs. two stents); (3) to guide all steps of percutaneous coronary intervention (PCI) (e.g., lesion preparation, decision of the landing zone, stent sizing, proximal optimization, side branch rewiring, kissing balloon); (4) to optimize stent result (e.g., expansion, apposition, geographical miss, major dissections). Although a growing body of data is already available on the use of OCT imaging for LM disease assessment and treatment, ongoing large prospective randomized trials will provide us with a more definitive evidence in this regard. These advances may substantially influence patient outcomes in what is a rapidly evolving field of coronary intervention.

Backgroud: The “FFR or OCT Guidance to Revascularize Intermediate Coronary Stenosis Using Angioplasty” (FORZA) trial showed that in patients with angiographically intermediate coronary lesions (AICLs), optical coherence tomography (OCT) guidance of percutaneous coronary intervention (PCI) reduced the occurrence of the composite endpoint of major adverse cardiac events (MACE) or significant angina at 13 months, while fractional flow reserve (FFR) guidance was associated with a higher rate of medical management and with lower costs. Safety of PCI deferral when FFR >0.80 is known, while data on clinical outcomes using an OCT guidance are lacking. We assessed the safety of PCI deferral based on OCT findings. Methods: This is a subgroups analysis of the FORZA Trial focusing on the clinical outcome of patients in whom PCI was originally deferred. In details, patients with AICLs were randomized to FFR or OCT imaging. In the FFR arm, PCI was deferred if FFR was >0.80 while in the OCT arm in the absence of any of the following conditions: area stenosis >75%, or 50% to 75% with minimum lumen area <2.5 mm2 or plaque rupture. Angina status (evaluated using the Seattle Angina Questionnaire, SAQ), MACE (death, myocardial infarction, target vessel revascularization) and rate of patients treated with optimal medical therapy alone were assessed at 24 months. Results: From a total of 350 patients with 446 AICLs enrolled in the trial (176 randomized to FFR and 174 to OCT), based on the predefined FFR and OCT criteria, PCI was deferred in 119 patients (67.6%) in the FFR arm, and in 82 patients (47.1%) in the OCT arm. At 24-months follow-up, significant residual angina (defined as a value <90 on the angina frequency scale) was observed in 6 patients (5.0%) in the FFR arm, and in 6 patients (7.3%) in the OCT arm (p = 0.55). Rate of MACE was 10.9% in the FFR arm and 6.1% in the OCT arm (p = 0.32). The number of patients managed by optimal medical therapy alone was still sig

Percutaneous coronary intervention (PCI) is considered a relatively safe procedure associated with low rates of complications, but is inevitably associated with short and mid-to-long term increased bleeding risk. Besides the short term risk associated with the arterial access to perform PCI, enhanced bleeding risk persists for several months, given the need for antithrombotic therapy to prevent procedure-related thrombotic complications as well as ischemic recurrences. Bleeding is a powerful harbinger of adverse outcomes. This awareness has fuelled intense research on bleeding reduction strategies, including new PCI devices and techniques as well as new medications and antithrombotic regimens. We here review the mechanisms and prevalence of bleeding in PCI patients, discuss the available evidence from a practical point of view, and explore future perspectives on how to treat and prevent bleeding complications in these patients.

Endothelial erosion of atherosclerotic plaques is the underlying cause of approximately 30% of acute coronary syndromes (ACS). As the vascular endothelium is profoundly affected by the haemodynamic environment to which it is exposed, we employed computational fluid dynamic (CFD) analysis of the luminal geometry from 17 patients with optical coherence tomography (OCT)-defined plaque erosion, to determine the flow environment permissive for plaque erosion. Our results demonstrate that 15 of the 17 cases analysed occurred on stenotic plaques with median 31% diameter stenosis (interquartile range 28–52%), where all but one of the adherent thrombi located proximal to, or within the region of maximum stenosis. Consequently, all flow metrics related to elevated flow were significantly increased (time averaged wall shear stress, maximum wall shear stress, time averaged wall shear stress gradient) with a reduction in relative residence time, compared to a non-diseased reference segment. We also identified two cases that did not exhibit an elevation of flow, but occurred in a region exposed to elevated oscillatory flow. Our study demonstrates that the majority of OCT-defined erosions occur where the endothelium is exposed to elevated flow, a haemodynamic environment known to evoke a distinctive phenotypic response in endothelial cells.

Background: Coronavirus disease 2019 (COVID-19) is a pandemic disease that is causing a public health emer gency. Characteristics and clinical significance of myocardial injury remain unclear. Methods: This retrospective single-center study analyzed 189 patients who received a COVID-19 diagnosis out of all 758 subjects with a high sensitive troponin I (Hs-TnI) measurement within the first 24 h of admission at the Policlinico A.Gemelli (Rome, Italy) between February 20th 2020 to April 09th 2020. Results: The prevalence of myocardial injury in our COVID-19 population is of 16%. The patients with cardiac injury were older, had a greater number of cardiovascular comorbidities and higher values of acute phase and inflammatory markers and leucocytes. They required more frequently hospitalization in Intensive Care Unit (10 [32.3%] vs 18 [11.4%]; p = .003) and the mortality rate was significantly higher (17 [54.8%] vs. 15 [9.5%], p < .001). Among patients in ICU, the subjects with myocardial injury showed an increase need of en dotracheal intubation (8 out of 9 [88%] vs 7 out of 19[37%], p = .042). Multivariate analyses showed that hs TnI can significantly predict the degree of COVID-19 disease, the intubation need and in-hospital mortality. Conclusions: In this study we demonstrate that hs-Tn can significantly predict disease severity, intubation need and in-hospital death. Therefore, it may be reasonable to use Hs-Tn as a clinical tool in COVID-19 patients in order to triage them into different risk groups and can play a pivotal role in the detection of subjects at high risk of cardiac impairment during both the early and recovery stage

Inflammation is the main pathophysiological process involved in atherosclerotic plaque formation, progression, instability, and healing during the evolution of coronary artery disease (CAD). The use of colchicine, a drug used for decades in non-ischemic cardiovascular (CV) diseases and/or systemic inflammatory conditions, stimulated new perspectives on its potential application in patients with CAD. Previous mechanistic and preclinical studies revealed anti-inflammatory and immunomodulatory effects of colchicine exerted through its principal mechanism of microtubule polymerization inhibition, however, other pleiotropic effects beneficial to the CV system were observed such as inhibition of platelet aggregation and suppression of endothelial proliferation. In randomized double-blinded clinical trials informing our clinical practice, low doses of colchicine were associated with the significant reduction of cardiovascular events in patients with stable CAD and chronic coronary syndrome (CCS) while in patients with a recent acute coronary syndrome (ACS), early initiation of colchicine treatment significantly reduced major adverse CV events (MACE). On the other hand, the safety profile of colchicine and its potential causal relationship to the observed increase in non-CV deaths warrants further investigation. For these reasons, postulates of precision medicine and patient-tailored approach with regards to benefits and harms of colchicine treatment should be employed at all times due to potential toxicity of colchicine as well as the currently unresolved signal of harm concerning non-CV mortality. The main goal of this review is to provide a balanced, critical, and comprehensive evaluation of currently available evidence with respect to colchicine use in the setting of CAD.

N/A

N/a

Endothelial erosion of atherosclerotic plaques is the underlying cause of approximately 30% of acute coronary syndromes (ACS). As the vascular endothelium is profoundly affected by the haemodynamic environment to which it is exposed, we employed computational fluid dynamic (CFD) analysis of the luminal geometry from 17 patients with optical coherence tomography (OCT)-defined plaque erosion, to determine the flow environment permissive for plaque erosion. Our results demonstrate that 15 of the 17 cases analysed occurred on stenotic plaques with median 31% diameter stenosis (interquartile range 28–52%), where all but one of the adherent thrombi located proximal to, or within the region of maximum stenosis. Consequently, all flow metrics related to elevated flow were significantly increased (time averaged wall shear stress, maximum wall shear stress, time averaged wall shear stress gradient) with a reduction in relative residence time, compared to a non-diseased reference segment. We also identified two cases that did not exhibit an elevation of flow, but occurred in a region exposed to elevated oscillatory flow. Our study demonstrates that the majority of OCT-defined erosions occur where the endothelium is exposed to elevated flow, a haemodynamic environment known to evoke a distinctive phenotypic response in endothelial cells.

AIMS: The ORal anticoagulants In fraGile patients with percutAneous endoscopic gastrostoMy and atrIal fibrillation (ORIGAMI) study investigates the safety and efficacy of Edoxaban administered via PEG in patients with atrial fibrillation and a clinical indication for a long-term anticoagulation. DESIGN: In this prospective, single-centre observational study, 12 PEG-treated patients with indication to anticoagulation will receive edoxaban via PEG and will be followed up to 6 months. Plasma antifactor Xa activity and edoxaban concentrations will be assessed. Thromboembolic (ischaemic stroke, systemic embolism, venous thromboembolism) and bleeding events (Bleeding Academic Research Consortium and Thrombolysis in Myocardial Infarction) will be recorded at 1 and 6 months. PRELIMINARY RESULTS: A retrospective analysis of five atrial fibrillation cases undergoing PEG implantation at our Institution who received edoxaban via PEG showed plasma anti-FXa levels at a steady state of 146 ± 15 ng/ml, without major adverse event at a mean follow-up of 6 months. CONCLUSION: ORIGAMI prospectively investigates PEG-administration of edoxaban in PEG-treated patients requiring long-term anticoagulation. Our preliminary retrospective data support this route of DOAC administration. CLINICALTRIALSGOV IDENTIFIER: NCT04271293.

For decades, we have known from autopsy observations that the proximate cause of the majority of acute coronary syndromes ( ACS) is occlusive thrombosis generated by plaque rupture or, less frequently, superficial erosion. Patients with ACS caused by plaque erosion seem to have a better long-term prognosis compared to those with plaque rupture, and may be stabilized by dual antiplatelet therapy without the need for stenting in a non-trivial proportion of cases, limiting the expenses and potential complications of invasive procedures. The accurate prediction of plaque erosion and the identification of specific biomarkers that could be used at the point-of-care without the need of invasive imaging would take us a step closer to the holy grail of precision medicine in patients with ACS.

Background: Contrast fractional flow reserve (cFFR) is a relatively new tool for the assessment of intermediate coronary artery stenosis and represents a reliable surrogate of FFR with the advantage of potentially simplifying functional evaluation. We aimed to compare the incidence of major adverse cardiac events (MACE) in patients undergoing functional evaluation with both FFR and cFFR based on the results of the two indexes. Method and Result: We retrospectively analyzed outcomes in 488 patients who underwent functional evaluation with FFR and cFFR. Patients were divided into four groups using the cutoff values of 0.80 for FFR and 0.85 for cFFR: −/− (n = 298), +/+ (n = 134), −/+(n = 31) and +/− (n = 25). All patients were treated according to FFR value. MACE rate was assessed in each group, including death, myocardial infarction and urgent target vessel revascularization (TVR). Mean follow-up time was 22 ± 15 months. Incidence of MACE at follow-up was 8.3% in FFR−/cFFR−, 14.0% in FFR+/cFFR+, 16.0% in FFR−/cFFR+ and 8.0% in FFR+/cFFR− without a significant difference amongst the 4 groups (p = 0.2). Nevertheless, a significant difference in the rate of TVR comparing FFR−/cFFR− (n = 17) and FFR−/cFFR+ (n = 5) was found at 24 months (5.7% vs 16.0%; p = 0.027). Conclusion: cFFR is accurate in predicting FFR and consequently reliable in guiding coronary revascularization. In the rare case of discordance, while FFR+/cFFR- patients show a prognosis similar to FFR-/cFFR- patients, FFR-/cFFR+ patients show a prognosis similar to FFR+/cFFR+ patients.

Although optical coherence tomography (OCT) proved to be able to identify macrophage clusters, there are no available data on the possibility to obtain reproducible measurements of their circumferential extension and location. The purpose of the present post-hoc analysis of the CLIMA study was to revise the clinical and demographic variables of patients having coronary plaques with macrophages and to investigate the reproducibility of their quantitative assessment. A total of 577 patients out of 1003 undergoing OCT showed macrophage accumulation. Three groups were identified; group 1 (426 patients) without macrophages, group 2 (296) patients with low macrophage content (less than median value [67°] of circumferential arc) and group 3 (281) with high macrophage content arc [> 67°]. Patients with macrophages (groups 2 and 3) showed a higher prevalence of family history for coronary artery disease and hypercholesterolemia and had a significantly larger body mass index. Furthermore, group 3 had more commonly triple vessel disease and higher value of LDL cholesterol levels compared to the two other groups. The inter-observer agreement for macrophage interpretation was good: R values were 0.97 for the circumferential arc extension, 0.95 for the minimum distance and 0.98 for the mean distance. A non-significant correlation between circumferential extension of macrophages and hsCRP values was found (R = 0.013). Quantitative assessment of macrophage accumulations can be obtained with high reproducibility by OCT. The presence and amount of macrophages are poorly correlated with hsCRP and identify patients with more advanced atherosclerosis and higher LDL cholesterol levels.

N/A

N/A

Aims Layered plaques represent signs of previous plaque destabilization. A recent study showed that acute coronary syndrome (ACS) patients with layered culprit plaque have more vulnerability at the culprit lesion and systemic inflammation. We aimed to compare the characteristics of non-culprit plaques between patients with or without layered plaque at the culprit lesion. We also evaluated the characteristics of layered non-culprit plaques, irrespective of culprit plaque phenotype. Methods We studied ACS patients who had undergone pre-intervention optical coherence tomography (OCT) imaging. The and results number of non-culprit lesions was evaluated on coronary angiogram and morphological characteristics of plaques were studied by OCT. In 349 patients, 99 (28.4%) had layered culprit plaque. The number of non-culprit plaques in patients with or without layered culprit plaque was similar (3.2 ± 0.8 and 2.8 ± 0.8, P = 0.23). Among 465 non-culprit plaques, 145 from patients with layered culprit plaque showed a higher prevalence of macrophage infiltration (71.0% vs. 60.9%, P = 0.050). When analysed irrespective of culprit plaque phenotype, layered non-culprit plaques showed higher prevalence of lipid (93.3% vs. 86.0%, P = 0.028), thin cap fibroatheroma (29.7% vs. 13.7%, P < 0.001), and macrophage infiltration (82.4% vs. 54.0%, P < 0.001) than non-layered plaques. Plaques with layered phenotype at both culprit and non-culprit lesions had the highest vulnerability. Conclusion In ACS patients, those with layered phenotype at the culprit lesion demonstrated greater macrophage infiltration at the non-culprit sites. Layered plaque at the non-culprit lesions was associated with more features of plaque vulnerability, particularly when the culprit lesion also had a layered pattern.

Refractory cardiogenic shock (RCS) or refractory cardiac arrest (RCA) complicating acute coronary syndrome (ACS) is associated with extremely high mortality rate. Veno-arterial extracorporeal life support (VA-ECLS) represents a valuable therapeutic option to stabilize patients’ condition before or at the time of emergency revascularization. We analyzed 29 consecutive patients with RCS or RCA complicating ACS, and implanted with VA-ECLS in two centers who have adopted a similar, structured approach to ECLS implantation. Data were collected from January 2010 to December 2015 and ECLS had to be percutaneously implanted either before (within 48 h) or at the time of attempted percutaneous coronary revascularization (PCI). We investigated in-hospital outcome and factors associated with survival. Twenty-one (72%) were implanted for RCA, whereas 8 (28%) were implanted on ECLS for RCS. All RCA were witnessed and no-flow time was shorter than 5 min in all cases but one. All patients underwent attempted emergency PCI, using radial access in ten cases (34.5%), whereas in three patients a subsequent CABG was performed. Overall, ten patients (34.5%) survived, nine of them with a good neurological outcome. Life threatening complications, including stroke (4 pts), leg ischemia (4 pts), intestinal ischemia (5 pts), and deep vein thrombosis 2 pts), occurred frequently, but were not associated with in-hospital death. Main cause of death was multi-organ failure. PCI variables did not predict survival. Survivors were younger, with shorter low-flow time, and with ECLS mainly implanted for RCS. At multivariate analysis, levels of lactate at ECLS implantation (OR 4.32, 95%CI 1.01–18.51, p = 0.049) emerged as the only variable that independently predicted survival. In patients with RCA or RCS complicating ACS who are percutaneously implanted with ECLS before or at the time of coronary revascularization, in hospital survival rate is higher than 30%. Level of lactate at ECLS im

AIMS: The goal of the present post hoc analysis of the CLIMA registry was to establish the relationship between calcified nodules (CNs) with (CND) or without (CNWD) disruption of the superficial intimal fibrous layer and one-year occurrence of target lesion myocardial infarction (MI) and/or cardiac death. METHODS AND RESULTS: CND and CNWD were identified based on the presence or absence of superficial irregularities indicative of disruption of the intimal fibrous layer, with possible overlying local thrombus. In total, 222 CNs were found in the 1,776 non-culprit LAD plaques. CND had larger maximum calcific arc and smaller lumen area. Cardiac death and MI occurred in 20% of patients in the CND group versus 2.7% in the CNWD group and 3.3% in the group without CN (p<0.001). This figure was mainly due to the 13.3% incidence of cardiac death in the CND group versus 2.0% in the CNWD group and versus 2.2% in the group without CN (p<0.001). The presence of CND was confirmed as an independent predictor of events (HR 6.58, 95% CI: 2.7-15.8, p<0.001). CONCLUSIONS: The presence of CND was associated with a high one-year incidence of cardiac death and/or target lesion MI.

N/A

Atherosclerotic plaques typically develop over a period of years or decades. In contrast, the thrombotic complications of atherosclerotic disease occur suddenly, often without warning.1 The notion that acute coronary syndromes develop from the rupture or superficial erosion of an atherosclerotic plaque is an oversimplification of a process involving plaque activity, blood thrombogenicity, and healing.2,3 Pathological studies have shown that many (if not most) atherosclerotic plaques destabilize without resulting in a clinical syndrome.4,5 The occurrence of an acute coronary syndrome probably depends on the disruption of a balance between instability ("activation") and healing ("passivation") of an atherosclerotic plaque. During the past 30 years, research efforts have mostly been focused on the mechanisms of plaque instability.2,3 Yet the risk of acute myocardial infarction or sudden death from coronary causes remains difficult to predict,6 suggesting that other pathogenic mechanisms should also be investigated. Recently, the notion that plaque healing may play a key role in the natural history of atherosclerotic disease has been gaining attention, in part because of the development of new imaging techniques, allowing in vivo study of the morphologic features of atherosclerotic plaque.7,8 This review examines the mechanisms of atherosclerotic plaque healing, their role in the progression of atherosclerotic disease and in the development of acute coronary syndromes, and the clinical and potential therapeutic implications of the healing process.

Aims: Despite the increasing use of early invasive strategies in non-ST-elevation acute coronary syndromes (NSTE-ACS), optimal initial antithrombotic therapy (ATT) based on the safety/efficacy profile of all guideline-recommended combinations remains crucial for the early management of both medically and invasively treated NSTE-ACS patients. Methods and results: Randomized controlled trials on ATT in NSTE-ACS/unstable angina reporting early (within 14 days) major adverse cardiovascular events (MACE) and major bleeding were selected. Overall, 3799 studies were screened, 117 clinical trials were assessed as potentially eligible, 20 trials were included in the study. According to treatment and type of intervention, nine different meta-analyses were performed including a total of 88 748 patients. A significant reduction of trial-defined MACE was found for aspirin vs. placebo [odds ratio (OR), 0.57; 95% confidence interval (CI), 0.34-0.96], heparin vs. placebo (OR, 0.38; 95% CI, 0.15-0.97), aspirin + heparin vs. placebo (OR, 0.32; 95% CI, 0.18-0.59), aspirin + heparin vs. aspirin (OR, 0.57; 95% CI, 0.42-0.79), aspirin + low molecular weight heparin (LMWH) vs. aspirin + unfractionated heparin (UFH; OR, 0.81; 95% CI, 0.69-0.95) and aspirin + ticagrelor/prasugrel + heparins vs. aspirin + clopidogrel + heparins (OR, 0.76; 95% CI, 0.62-0.94). A significant decrease in major bleeding was found only for fondaparinux vs. LMWH on the background of aspirin + clopidogrel (OR, 0.52; 95% CI, 0.44-0.62) despite a clear trend towards increased bleeding for heparin compared to aspirin, aspirin + heparin compared to placebo, aspirin + heparin compared to aspirin, aspirin + P2Y12inhibitors + UFH/LMWH compared to aspirin + UFH/LMWH, and aspirin + ticagrelor/prasugrel + heparins compared to aspirin + clopidogrel + heparins. Conclusion: To our knowledge, these findings are the first to report the safety and efficacy of all the various combinations of currently recommended ATT for the early m

•The optimal antithrombotic regimen to be used in patients with AF and PCI or ACS is still debated.•Each of the six randomised controlled trials comparing double to triple therapy has limitations.•None was powered to assess differences between treatment arms in ischaemic event rates.•The contrasting results regarding ischaemic events within published meta-analyses can be explained by heterogeneity, incompleteness and varying definitions of stent thrombosis.•The overall reduced bleeding rates, but increased early definite and probable stent thrombosis rates with double versus triple antithrombotic therapy encourage consideration of triple therapy during the first weeks from PCI followed by double therapy.

Background: Coronary vasomotor dysfunction represents an important mechanism responsible for myocardial ischaemia in patients with non-obstructive coronary artery disease (CAD). The use of invasive provocative tests allows identifying patients with epicardial or microvascular spasm. Of note, clinical characteristics associated with the occurrence of epicardial or microvascular spasm have still not completely clarified. Methods and results: We prospectively enrolled consecutive patients undergoing coronary angiography for suspected myocardial ischaemia/necrosis with evidence of non-obstructive CAD and undergoing intracoronary provocative test for suspected vasomotor dysfunction. Patients with a positive provocative test were enrolled. Clinical, echocardiographic and angiographic characteristics of patients were evaluated according to the pattern of vasomotor dysfunction (epicardial vs. microvascular spasm). We included 120 patients [68 patients with stable angina and 52 patients with myocardial infarction and non-obstructive coronary arteries (MINOCA)]. In particular, 77 (64.2%) patients had a provocative test positive for epicardial spasm and 43 (35.8%) patients for microvascular spasm. Patients with epicardial spasm were more frequently males, smokers, had higher rates of diffuse coronary atherosclerosis at angiography and more frequently presented with MINOCA. On the other hand, patients with microvascular spasm presented more frequently diastolic dysfunction. At multivariate logistic regression analysis male sex, smoking, and diffuse coronary atherosclerosis were independent predictors for the occurrence of epicardial spasm. Conclusions: Our study showed that specific clinical features are associated with different responses to intracoronary provocative test. Epicardial spasm is more frequent in males and in MINOCA patients, whereas microvascular spasm is more frequent in patients with stable angina and is associated with diastolic dysfunction.

N/A

Objectives: The aim of this study was to compare optical coherence tomographic (OCT) guidance and fractional flow reserve (FFR) guidance in patients with angiographically intermediate coronary lesions (AICLs) in a single-center, prospective, 1:1 randomized trial. Background: FFR and OCT imaging may help both in the assessment of AICLs and in percutaneous coronary intervention optimization. Methods: Patients with AICLs were randomized to FFR or OCT imaging. In the FFR arm, PCI was performed if FFR was ≤0.80. In the OCT imaging arm, PCI was performed if area stenosis was ≥75% or 50% to 75% with minimal luminal area <2.5 mm2 or plaque rupture. Angina (evaluated using the Seattle Angina Questionnaire), major adverse cardiac events, and cost were assessed at the end of follow-up. The pre-defined primary endpoint was the composite of major adverse cardiac events or significant angina (defined as Seattle Angina Questionnaire frequency scale score <90) at 13 months. Results: A total of 350 patients (with 446 AICLs) were enrolled (176 randomized to FFR and 174 to OCT imaging). The primary endpoint of major adverse cardiac events or significant angina at 13 months occurred in 14.8% of patients in the FFR arm and in 8.0% in the OCT imaging arm (p = 0.048). This result was driven by a statistically nonsignificant lower occurrence of all primary endpoint components. Up to 13 months, the rate of medically managed patients was significantly higher (p < 0.001) and total cost significantly lower (p < 0.001) with FFR in comparison with OCT imaging. Conclusions: In patients with AICLs, OCT guidance is associated with lower occurrence of the composite of major adverse cardiac events or significant angina. FFR guidance is associated with a higher rate of medical management and lower costs. FFR or OCT Guidance to Revascularize Intermediate Coronary Stenosis Using Angioplasty [FORZA]; NCT01824030)

Background: Ticagrelor is a reversibly binding, direct-acting, oral, P2Y12 antagonist used for the prevention of atherothrombotic events in patients with coronary artery disease (CAD). Ticagrelor blocks adenosine reuptake through the inhibition of equilibrative nucleoside transporter 1 (ENT-1) on erythrocytes and platelets, thereby facilitating adenosine-induced physiological responses such as an increase in coronary blood flow velocity. Meanwhile, adenosine plays an important role in triggering ischemic preconditioning through the activation of the A1 receptor. Therefore, an increase in ticagrelor-enhanced adenosine bioavailability may confer beneficial effects through mechanisms related to preconditioning activation and improvement of coronary microvascular dysfunction. Methods: To determine whether ticagrelor can trigger ischemic preconditioning and influence microvascular function, we designed this prospective, open-label, pilot study that enrolled patients with stable multivessel CAD requiring staged, fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI). Participants will be randomized in 1:1 ratios either to ticagrelor (loading dose (LD) 180 mg, maintenance dose (MD) 90 mg bid) or to clopidogrel (LD 600 mg, MD 75 mg) from 3 to 1 days before the scheduled PCI. The PCI operators will be blinded to the randomization arm. The primary endpoint is the delta (difference) between ST segment elevations (in millimeters, mm) as assessed by intracoronary electrocardiogram (ECG) during the two-step sequential coronary balloon inflation in the culprit vessel. Secondary endpoints are 1) changes in coronary flow reserve (CFR), index of microvascular resistance (IMR), and FFR measured in the culprit vessel and reference vessel at the end of PCI, and 2) angina score during inflations. This study started in 2018 with the aim of enrolling 100 patients. Based on the rate of negative FFR up to 30% and a drop-out rate up to 10%, we expect to detect an absolu

Importance: At one end of the coronary artery disease (CAD) spectrum, there are patients with multiple recurrent acute coronary syndromes (rACS), and at the other end there are those with long-standing clinical stability. Predicting the natural history of these patients is challenging because unstable plaques often heal without resulting in ACS. Objective: To assess in vivo the coronary atherosclerotic phenotype as well as the prevalence and characteristics of healed coronary plaques by optical coherence tomography (OCT) imaging in patients at the extremes of the CAD spectrum. Design, Setting, and Participants: This is an observational, single-center cohort study with prospective clinical follow-up. From a total of 823 consecutive patients enrolled in OCT Registry of the Fondazione Policlinico A. Gemelli-IRCCS, Rome, Italy, from March 2009 to February 2016, 105 patients were included in the following groups: (1) patients with rACS, defined as history of at least 3 acute myocardial infarctions (AMIs) or at least 4 ACS with at least 1 AMI; (2) patients with long-standing stable angina pectoris (ls-SAP), defined as a minimum 3-year history of stable angina; and (3) patients with a single unheralded AMI followed by a minimum 3-year period of clinical stability (sAMI). Data were analyzed from January to August 2018. Exposures: Intracoronary OCT imaging of nonculprit coronary segments. Main Outcomes and Measures: Coronary plaque features and the prevalence of healed coronary plaques in nonculprit segments as assessed by intracoronary OCT imaging. Results: Of 105 patients, 85 were men (81.0%); the median (interquartile range) age was 68 (63-75) years. Median (interquartile range) time of clinical stability was 9 (5.0-15.0) years in the ls-SAP group and 8 (4.5-14.5) years in the sAMI group. Patients in the rACS and sAMI groups showed similar prevalence of lipid-rich plaque and thin-cap fibroatheroma, which was significantly higher than in those with ls-SAP (lipid-rich plaqu

Background: Fractional flow reserve (FFR) and optical coherence tomography (OCT) may help both in assessment and in percutaneous coronary intervention optimization of angiographically intermediate coronary lesions. We designed a prospective trial comparing the clinical and economic outcomes associated with FFR or OCT in angiographically intermediate coronary lesions. Methods and Results: Three hundred fifty patients with angiographically intermediate coronary lesions (n=446) were randomized to FFR or OCT guidance. In the FFR arm, percutaneous coronary intervention was performed if FFR was ≤0.80 aiming for a postprocedure FFR >0.90. In the OCT arm, percutaneous coronary intervention was performed if percentage of area stenosis was ≥75% or 50% to 75% with minimal lumen area <2.5 mm2 or plaque ulceration. Costs, angina frequency, and major adverse cardiac events were assessed at 1 month and at 13 months. We present early data at 1 month consistent with a prespecified analysis of secondary end points. Patients randomized to FFR, as compared with OCT, were significantly more commonly managed with medical therapy alone (67.7% versus 41.1%; P<0.001), required less contrast media (245±137 versus 280±129 mL; P=0.004), and exhibited a lower occurrence of contrast-induced acute kidney injury (1.7% versus 8.6%; P=0.034). At 1 month, in comparison to FFR, OCT was associated with increased total costs (2831±1288 versus 4292±3844 euros/patient; P<0.001) whereas occurrence of major adverse cardiac events or significant angina was similar. Conclusions: In patients with angiographically intermediate coronary lesions, a functional guidance by FFR, as compared with OCT, increased the rate of patients treated with medical therapy alone. This translated into a significant reduction in administered contrast, contrast-induced acute kidney injury, and total costs at 1 month with FFR. Clinical Trial Registration: URL: http://www.clinicaltrialsgov. Un

N/A

Anticoagulant therapy during the acute phase of non-ST elevation acute coronary syndromes (NSTE-ACS) is strongly recommended by current international guidelines. Evidence supporting the use of anticoagulant therapy in the early phase of NSTE-ACS however, is based on dated trials mostly performed in the nineties and recent randomised clinical trials (RCTs), performed during the last 15 years, clearly evidence a dichotomy in the investigation of antiplatelet and anticoagulant strategies. Many innovations have since occurred in the diagnosis and management of NSTE-ACS. Since a RCT evaluating the efficacy of anticoagulant therapy versus placebo in a contemporary setting of NSTE-ACS management is lacking, we provide a systematic review of 1) the randomised data for ATT in the early phase of NSTE-ACS; 2) modern international guidelines, and 3) contemporary clinical practice data. The results are analysed and potential treatment and research strategies are proposed. (c) 2018 Elsevier B.V. All rights reserved.

Background: Dual quantitative coronary angiography (QCA) has been recently tested for assessment of intracoronary thrombus volume in experimental models. The present study aimed to validate dual QCA in vivo for the assessment of thrombus burden by exploring the correlations between dual QCA-thrombus volume and optical coherence tomography (OCT)-derived indices of thrombotic burden.Methods and results: Fifty-one patients with ACS and angiographic evidence of thrombus undergoing OCT of the culprit lesion before stenting were included. Dual QCA-thrombus volume was calculated as difference between edge-detection and video-densitometry area functions along the target segment. Culprit lesion was categorized using the Ambrose's and AHA/ACC angiographic classifications. Thrombus volume (mean thrombus area x thrombus length), thrombus burden [(mean thrombus area/mean lumen area) x 100] and Prati thrombus score (number of quadrants with thrombus) were measured by OCT, and the presence of plaque rupture (PR) or intact fibrous cap (IFC) was assessed. Dual QCA-thrombus volume correlated significantly with OCT-thrombus volume (R = 0.791), thrombus burden (R = 0.767) and Prati thrombus score (R = 0.600) (all p < 0.001). Dual-QCA thrombus volume was significantly higher in patients with PR compared with those with IFC (3.48 mm(3) [1.45-11.26] vs. 1.69 mm(3) [0.09-5.02], p=0.013). Compared with IFC, PR showed higher prevalence of eccentric type II Ambrose lesion (41.7% vs. 7.4%, p = 0.004), complex B2/C lesion (87.5% vs. 55.6%, p=0.012), and heavy calcification (29.2% vs. 3.7%, p=0.013).Conclusions: Dual QCA analysis appears to be a promising tool for quantification of intracoronary thrombus in vivo. This novel methodology may be useful to guide intracoronary thrombus removal during percutaneous coronary intervention and to aid prognostic stratification in patients with ACS. (C) 2019 Elsevier B.V. All rights reserved.

The recognition that obstructive disease of the epicardial coronary arteries, causing ischaemic heart disease, can be treated with a percutaneous coronary intervention (PCI) has been a major discovery in cardiology in the last 40 years contributing, in particular, to the reduction of mortality associated to acute myocardial infarction (AMI). However, even in the era of drug-eluting stent (DES) implantation, a sizable proportion of patients who undergo PCI may develop late or very late post-implantation complications, that occur in the form of restenosis, neoatherosclerosis, and/or in-stent thrombosis. Such complications are clinically relevant since they can cause AMI and negatively impact on the outcome. The underlying pathophysiological mechanisms are complex but related to inhibition of neointimal proliferation by DES that, on the hand, reduces the rate of in-stent restenosis, but, on the other hand, causes dysfunctional vessel healing, persistent inflammation, platelet activation, and adverse immunological responses. Multiple approaches have been developed or are under evaluation to target DES-related complications including pharmacotherapy, procedure-related imaging methods, novel stent designs, and drug-delivery methods. The aim of this review is to provide an update on the latest preclinical, translational, and clinical pharmacotherapeutic developments in this setting that target novel cellular mechanisms and pathways that might contribute to neoatherosclerosis. Due to the importance of secondary prevention in the reduction of DES-associated complications, this review also provides a short overview of pharmacological agents that are established or currently being investigated in this regard.

Extensive data support the safety of direct oral anticoagulants compared with vitamin K antagonists in patients with non-valvular atrial fibrillation, leading to a significantly increase in the use of these compounds in clinical practice. However, there is no compelling evidence supporting the use of direct oral anticoagulant in individuals who are intubated or have a percutaneous endoscopic gastrostomy (PEG): patients with several co-morbidities are underrepresented in clinical trials, so the best long-term strategy for anticoagulation is difficult to ascertain. The aim of the present report was to evaluate the safety and efficacy of edoxaban administered via PEG in a patient with heart failure and a history of atrial fibrillation affected by amyotrophic lateral sclerosis (ALS). A 71-year-old man with atrial fibrillation, advanced ALS, type II diabetes mellitus, and hypertension presented to the emergency department with dyspnoea and tachycardia. Because vitamin K antagonist and rivaroxaban 15 mg were dropped because of difficult international normalized ratio control (time in therapeutic range <30%) and severe haematuria, respectively, edoxaban 30 mg (crushed pill) daily was administered based on the patient's weight of 58 kg. Mean edoxaban plasma concentration–time profiles were measured, as anti-Xa activity, 2 h before and at 2, 6, and 22 h after drug administration and then compared with the pharmacokinetic profile of edoxaban 30 mg in healthy subjects. An additional testing of steady-state peak plasma concentration of edoxaban after 10 days and a 30 day follow-up were evaluated. The values of the pharmacokinetic parameters, analysed with a non-compartmental analysis by PKSolver module, showed that Cmax and AUC0→t were only slightly higher than those observed in healthy subjects, while the half-life and observed clearance were significantly longer and lower, respectively, than in normal subjects. Steady-state peak plas