Electrical storm treatment by percutaneous stellate ganglion block: the STAR study.

BACKGROUND AND AIMS: An electrical storm (ES) is a clinical emergency with a paucity of established treatment options. Despite initial encouraging reports about the safety and effectiveness of percutaneous stellate ganglion block (PSGB), many questions remained unsettled and evidence from a prospective multicentre study was still lacking. For these purposes, the STAR study was designed. METHODS: This is a multicentre observational study enrolling patients suffering from an ES refractory to standard treatment from 1 July 2017 to 30 June 2023. The primary outcome was the reduction of treated arrhythmic events by at least 50% comparing the 12 h following PSGB with the 12 h before the procedure. STAR operators were specifically trained to both the anterior anatomical and the lateral ultrasound-guided approach. RESULTS: A total of 131 patients from 19 centres were enrolled and underwent 184 PSGBs. Patients were mainly male (83.2%) with a median age of 68 (63.8-69.2) years and a depressed left ventricular ejection fraction (25.0 ± 12.3%). The primary outcome was reached in 92% of patients, and the median reduction of arrhythmic episodes between 12 h before and after PSGB was 100% (interquartile range -100% to -92.3%). Arrhythmic episodes requiring treatment were significantly reduced comparing 12 h before the first PSGB with 12 h after the last procedure [six (3-15.8) vs. 0 (0-1), P < .0001] and comparing 1 h before with 1 h after each procedure [2 (0-6) vs. 0 (0-0), P < .001]. One major complication occurred (0.5%). CONCLUSIONS: The findings of this large, prospective, multicentre study provide evidence in favour of the effectiveness and safety of PSGB for the treatment of refractory ES.

Real-world data of patients affected by advanced heart failure treated with implantable cardioverter defibrillator and left ventricular assist device: Results of a multicenter observational study.

BACKGROUND: Left ventricular assist device (L-VAD) implantation is increasingly used in patients with heart failure (HF) and most patients also have an implantable cardioverter defibrillator (ICD). Limited data are available on the incidence of ICD therapies and complications in this special setting. The aim of this study was to analyze the real-world incidence and predictors of ICD therapies, complications and interactions between ICD and L-VAD. METHODS: We conducted a multicenter retrospective observational study in patients with advanced HF implanted with ICD and a continuous-flow L-VAD, followed-up in five advanced HF centers in Northern Italy. RESULTS: A total of 234 patients (89.7% male, median age 59, 48.3% with ischemic etiology) were enrolled. After a median follow-up of 21 months, 66 patients (28.2%) experienced an appropriate ICD therapy, 22 patients (9.4%) an inappropriate ICD therapy, and 17 patients (7.3%) suffered from an interaction between ICD and L-VAD. The composite outcome of all ICD-related complications was reported in 41 patients (17.5%), and 121 (51.7%) experienced an L-VAD-related complication. At multivariable analysis, an active ventricular tachycardia (VT) zone and a prior ICD generator replacement were independent predictors of ICD therapies and of total ICD-related complications, respectively. CONCLUSIONS: Real-world patients with both L-VAD and ICD experience a high rate of ICD therapies and complications. Our findings suggest the importance of tailoring device programming in order to minimize the incidence of unnecessary ICD therapies, thus sparing the need for ICD generator replacement, a procedure associated to a high risk of complications.

Among biomarkers of neutrophil activity, matrix metalloproteinases 8 independently predicts remission of metabolic syndrome.

BACKGROUND AND AIMS: Inflammation due to the excess of nutrient intake plays an important role in the pathophysiology of metabolic syndrome (MetS). Here, the potential influence of neutrophils and their degranulation markers on MetS improvement upon dietary and behavioral counselling, has been investigated. Specifically, we aimed at investigating their role as potential predictors of metabolic syndrome improvements. METHODS AND RESULTS: patients with MetS (n = 127) received behavioral and dietary recommendations before follow-up at 6 months. Serum levels of matrix metalloproteinases (MMP)8, MMP9, myeloperoxidase (MPO), tissue inhibitor of MMP (TIMP)-1, TIMP-2, TIMP-3 and resistin were tested at baseline. In the whole cohort, baseline levels of proinflammatory MMP8, MMP9 and MPO increased together with the number of MetS criteria. Seventy-three (57%) patients experienced a reduction in MetS-defining criteria at follow-up. With respect to those with no improvement, such individuals showed lower weight and waist circumference at enrolment, less frequent smoking habits, higher levels of triglycerides and lower circulating MMP8. At logistic regression analysis, baseline MMP8 showed negative predictive ability (odds ratio (OR) 0.979 [0.961-0.997]; p = 0.025) against MetS improvement. Such findings hold true even when included in the backward stepwise logistic regression model confirming MMP8 as an independent predictor (OR 0.970 [0.949-0.993]; p = 0.009). Receiver operating characteristic (ROC) curve confirmed the predictive ability of MMP8 combined in a model including baseline MetS criteria and waist circumference. Bootstrap resampling analysis internally validated our findings. CONCLUSION: Improvement of MetS is independently associated with baseline low MMP-8 levels, suggesting a pivotal role for inflammation in metabolic alteration.

Minor amputation after revascularization in chronic limb-threatening ischemia: What is the optimal timing?

OBJECTIVES: Patients with chronic limb-threatening ischemia (CLTI) have a high risk of lower limb amputation and loss of walking independence. Minor amputations play a key role in ensuring walking independence and they represent a challenge in terms of timing and level for vascular surgeons. A major cause of re-amputation is a defect in wound healing and a possible predictor of re-amputation for non-healing wounds could be the incorrect timing of minor amputation after revascularization. The lack of evidence in the literature leads to a wide variability of choices in clinical practice. The purpose of this study was to try to find the optimal timing analysing the risk of re-amputation in CLTI patients who have undergone successful revascularization and minor amputation focussing on timing of minor amputation. METHODS: We conducted a single centre retrospective analysis on a cohort of 151 patients consecutively admitted to our hospital for CLTI (Rutherford 5) between January 2014 and April 2022. All the enrolled patients underwent successful revascularization of lower limbs and a minor amputation for dry acral necrosis. The characteristics of the patients and the revascularization procedures were collected and analysed. Patients were divided into two groups based on the timing of minor amputation performed before (group 1) or after the day (group 2) that best predicts the risk of re-amputation according to a Receiver Operating Characteristic (ROC) curve analysis. The primary outcome of this study was the risk of re-amputation during the first 60 days of follow-up after a primary minor amputation, with revascularization still effective. The impact of the timing of minor amputation after revascularization, the type of revascularization and the presence of risk factors known to prolong the wound healing process were evaluated in a uni- and multi-variable logistic regression model. RESULTS: Systemic hypertension, and type of revascularization (i.e. open vs endovascular) were independent predictors of the risk of re-amputation at 60 days (HR 4.26, 95% CI 1.30-14.04, p = .017 and HR 2.35, 95% CI 1.16-4.78, p = .018, respectively). Moreover, time ≤14 days between revascularization and first amputation was associate with a clear, albeit not statistically significant, trend toward increased risk of re-amputation (HR 2.09, 95% CI 0.97-4.51, p = .06). CONCLUSIONS: In a cohort of patients who underwent a successful revascularization for CLTI and a minor amputation for dry gangrene in the first 14 days after revascularization, a higher -although not significant-risk of re-amputation was reported. In this cohort of patients, a delayed demolitive procedure should be considered to allow better tissue perfusion and to reduce the risk of re-amputation.

Serum osteopontin predicts glycaemic profile improvement in metabolic syndrome: A pilot study.

Prediabetes is often observed in patients with Metabolic Syndrome (MetS) and might be associated with metabolic and inflammatory alterations. Here, we investigated whether the inflammatory molecule osteopontin (OPN) might have a prognostic impact in a cohort of MetS patients (n = 85) with baseline normal glycaemia or impaired fasting glucose (IFG) over one year of recommended pharmacological treatments and Mediterranean diet. Patients were then followed up for 12 months with intermediate evaluation after 6 months. At all time points, anthropometric and clinical data were recorded, alongside with haematological and biochemical profiles, including serum concentrations of OPN. As expected, Mediterranean diet improves glycaemic profile in patients with IFG. Baseline serum OPN failed to be associated with baseline anthropometric or biochemical variables. At baseline, higher levels of OPN were shown in patients with IFG as compared to normal glycaemia. Two distinct subgroups of patients in whom OPN decreased or remained stable/increased at follow-up were identified. When higher serum OPN levels were observed at baseline, greater reduction was observed at 1-year follow-up. Reduction in circulating OPN levels was associated with metabolic improvement in terms of blood pressure, LDL-c, HDL-c, and glycaemia. At both univariate and adjusted logistic regression analyses, serum OPN emerged as an independent predictor of glycaemic profile improvement at 1-year follow-up (adjOR 1.05 [1.00-1.10]; P = .041). In conclusion, pharmacological and dietetic interventions improved glycaemic profile in patients with MetS. In particular, glycaemic improvement was demonstrated in patients who also reduce circulating OPN levels. Higher OPN levels at baseline predict normalization of glycaemic profile.

Atrial fibrillation in advanced renal failure: are there alternative solutions to warfarin-dicumarol?

Patients with atrial fibrillation (AF) and chronic renal failure (CRF) represent a growing population in epidemiological terms since both conditions increase with advancing age. The association of AF and CRF is burdened with a poor prognosis and with a high risk of adverse events, both ischaemic and haemorrhagic. Oral anticoagulant therapy, in these patients, is more problematic, especially due to the concomitant increased risk of bleeding. The use of direct oral anticoagulants (DOACs) in patients with non-severe renal insufficiency appears to be safe and effective. Since all currently available DOACs are at least partially eliminated by the kidney (dabigatran is the direct anticoagulant with the highest rate of renal elimination, approximately 80%), periodic monitoring of renal function is recommended to evaluate possible need for dosage adjustment. In patients with advanced renal insufficiency, the use of DOAC appears controversial, given the small number of clinical studies that have tested its efficacy and safety. It is known, however, that oral anticoagulation therapy with vitamin K antagonists (VKAs) is associated with an increase in nephropathy and renal-vascular calcification. From this point of view, therapy with DOAC could be more advantageous than VKAs. Data from clinical studies would seem to show that the use of dabigatran and rivaroxaban in these patients may lead to a reduction in the inevitable deterioration of renal function.

Baseline hs-CRP predicts hypertension remission in metabolic syndrome.

BACKGROUND: Inflammation, overweight and other cardiovascular risk factors might negatively impact on hypertension remission in metabolic syndrome (MetS), independently of the pharmacological treatment. Here, the potential influence of systemic inflammation (assessed by serum high-sensitivity C-reactive protein [hs-CRP]) on hypertension remission will be investigated in a cohort of hypertensive patients with MetS. MATERIAL AND METHODS: Hypertensive patients with MetS (n = 100) were enrolled, treated under current behavior/dietary/pharmacological recommendations and followed up for 12 months. All patients received medications and nutritional advice based on Mediterranean-like dietary pattern in addition to psychological and physical activity counselling. At baseline (T0), 6 (T1) and 12 (T2) months of follow-up, clinical data, haematological and biochemical profiles and serum hs-CRP were measured. RESULTS: As compared to T0, at T2 patients displayed improvements in anthropometric and metabolic profiles. At T2, the hypertension remission rate was 13.0%. Serum hs-CRP did not change overtime in the overall cohort. Surprisingly, patients who experienced hypertension remission were less treated with antihypertensive drugs, but developed a weak improvement in anthropometric measures during follow-up. The hypertension remission group had lower baseline levels of hs-CRP as compared to non-remission. Low baseline hs-CRP (<2 µg/mL, cut-off value identified by ROC curve) predicted hypertension remission, independently of antihypertensive treatment implementation, baseline systolic blood pressure and waist circumference improvement. CONCLUSIONS: Remission of hypertension in MetS is independently associated with baseline low CRP levels, which might suggest a critical role for inflammation in sustaining high blood pressure levels.

The Role of Adipocytokines in Coronary Atherosclerosis.

PURPOSE OF REVIEW: The aim of this review is to overview the pathophysiological role of adipocytokines in atherogenesis, focusing on their potential role as biomarkers of coronary disease. RECENT FINDINGS: Several lines of evidence indicated adipose tissue not only as depot but rather as an endocrine organ. In this context, the balance between pro- and anti-inflammatory adipocytokines has been shown to critically regulate vascular homeostasis in both physiological and pathophysiological conditions. Overweight and obesity are characterized by dysfunctional adipose tissue and then the prevalence of pro-inflammatory mediators, with a detrimental effect on vascular health. As opposite to adiponectin, pro-inflammatory adipocytokines, such as leptin and resistin, promote endothelial dysfunction and inflammatory processes involved in atherosclerotic plaque progression and vulnerability. Therefore, many adipocytokines have been investigated as potential biomarkers of cardiovascular (CV) risk, but their role has not yet been clearly established. Furthermore, the perivascular adipose tissue recently emerged as a critical modulator of atherosclerotic processes, due to the close interaction with the underlying vascular tissue. The ongoing discovery of new adipocytokines and the complex pathophysiological role of the different adipose tissue depots strongly contribute to define the complexity of adipocytokines network. Understanding those complex interactions may allow determining new potential biomarkers of CV risk and potential therapeutic targets.

Update on Inflammatory Biomarkers and Treatments in Ischemic Stroke.

After an acute ischemic stroke (AIS), inflammatory processes are able to concomitantly induce both beneficial and detrimental effects. In this narrative review, we updated evidence on the inflammatory pathways and mediators that are investigated as promising therapeutic targets. We searched for papers on PubMed and MEDLINE up to August 2016. The terms searched alone or in combination were: ischemic stroke, inflammation, oxidative stress, ischemia reperfusion, innate immunity, adaptive immunity, autoimmunity. Inflammation in AIS is characterized by a storm of cytokines, chemokines, and Damage-Associated Molecular Patterns (DAMPs) released by several cells contributing to exacerbate the tissue injury both in the acute and reparative phases. Interestingly, many biomarkers have been studied, but none of these reflected the complexity of systemic immune response. Reperfusion therapies showed a good efficacy in the recovery after an AIS. New therapies appear promising both in pre-clinical and clinical studies, but still need more detailed studies to be translated in the ordinary clinical practice. In spite of clinical progresses, no beneficial long-term interventions targeting inflammation are currently available. Our knowledge about cells, biomarkers, and inflammatory markers is growing and is hoped to better evaluate the impact of new treatments, such as monoclonal antibodies and cell-based therapies.

Left Atrial Anomalous Muscular Band: Case Report, Literature Review, and Role of Three-Dimensional Echocardiography.

Anomalous fibromuscular bands in the left atrium were already described in the 19th century. Recently, the greater attention to the anatomy of the left atrium and the technological improvement have made their finding more frequent. Here, we present six cases, out of approximately 30,000 unselected echocardiograms, in which the use of the three-dimensional echo allowed a better definition of their anatomy, course, and motility.

A comprehensive meta-analysis comparing radiofrequency ablation versus pharmacological therapy for the treatment of atrial fibrillation in patients with heart failure.

BACKGROUND: Atrial fibrillation (AF) and heart failure (HF) are both associated with worse prognosis and often coexist in the same patients. Whether catheter ablation (CA) is superior to pharmacological therapy in reducing major clinical endpoints in patients with AF and HF is still unsettled. OBJECTIVE: To conduct a comprehensive meta-analysis comparing CA with medical therapy (MT) in this population. METHODS: We systematically searched for randomized and observational studies comparing clinical outcomes between patients with AF and HF treated with CA or MT. The studied outcomes were mortality, hospitalization, left ventricle ejection fraction (LVEF) and 6-min walking test (6MWT) improvement. RESULTS: A total of 12 studies counting 41,377 patients (3611 treated with CA and 37,766 with MT) were included in the analysis. The random-effect model revealed a clear trend in favor of CA in reducing unexpected HF hospitalization (RR 0.72; 95%CI 0.51-1.00; P = 0.05), all-cause death (RR 0.77; 95%CI 0.59-1.01; P = 0.06), all-cause hospitalization (RR 0.84; 95%CI 0.68-1.03; P = 0.09), and the composite of HF hospitalization and death (RR 0.77; 95%CI 0.58-1.02; P = 0.07), compared with MT. Patients treated with CA experienced a better improvement in LVEF (mean difference 6.17; 95%CI 2.98-9.37; P = 0.0002) and 6MWT (mean difference 13.70; 95%CI 3.95-23.45; P = 0.006). When the analysis was limited to randomized controlled trial, CA was found to significantly reduce all-cause death (RR 0.68; 95%CI 0.54-0.86; P = 0.001). CONCLUSION: As compared to MT, CA is associated with a better improvement in functional capacity and LVEF, and with a reduction in major clinical endpoints in patients with HF and AF.

An annotation-independent algorithm based on electrogram characteristics to guide the identification of ventricular tachycardia isthmuses in patients with structural heart disease.

BACKGROUND: Criteria such as electrograms voltage or late potentials have been largely utilized in the past to help identify areas of substrate maps that are within the ventricular tachycardia (VT) isthmus; yet their specificity and positive predictive value are quite low. The Lumipoint fractionation tool of the Rhythmia system illuminates regions with fractionated electrograms irrespective of their timing and annotation. We aimed to ascertain whether the use of this tool can rapidly identify areas within VT isthmuses from substrate maps. METHODS: Thirty patients with structural cardiomyopathy in whom a complete right ventricular-paced substrate map and a full reconstruction of the diastolic isthmus during VT could be obtained were enrolled. The VT isthmus border was projected on each substrate map to verify whether the areas illuminated by Lumipoint fell within those borders. The behavior of the electrograms detected at the illuminated areas of the substrate maps was studied during a right ventricular drive train and extra stimulus protocol: if the near field potentials showed a delayed conduction after a single extra stimulus, defined as a minimum of 10 ms increase of the time interval between the far field and the near field activation measured during the drive train, the electrogram was said to have a "decremental" behavior. RESULTS: The logistic analysis showed that areas with fractionated electrograms illuminated by the Lumipoint software and showing the greatest decremental behavior fell within the VT isthmus borders (OR = 1.66, CI: 1.41-1.75, p<0.001; OR=1.57 CI: 1.32-1.72, p<0.001, respectively) with a sensitivity, specificity, and positive predictive value of 87%, 96%, and 97%, respectively. CONCLUSIONS: Fractionated electrograms illuminated by the automated Lumipoint software on right ventricular-paced substrate maps showing the greatest decremental behavior fall within the VT isthmus borders with a probability of 0.97, irrespective of their timing, annotation, or voltage, without any need for subjective assessment of their involvement in slow conduction areas.

Colchicine for cardiovascular medicine: a systematic review and meta-analysis.

Aim: Colchicine, a microtubule-disassembling (antitubulin) agent used for centuries for the treatment of gout and autoimmune diseases, is a drug of growing interest in the cardiovascular field. While in the last decades it has become cornerstone of pericarditis treatment, it has also emerged in the last few years as a promising drug in the management of coronary artery disease, atrial fibrillation and heart failure. This systematic review and meta-analysis aimed to assess the efficacy of colchicine in patients with cardiovascular diseases. Methods: Systematic search in electronic databases (MEDLINE/PubMed, Scopus, BioMed Central, the Cochrane Collaboration Database of Randomized Trials, ClinicalTrials.gov, EMBASE, Google Scholar) was performed to identify randomized controlled trials (RCTs) up to February 2021. Random-effects meta-analysis was performed to assess the risk of cardiovascular events, defined according to clinical setting. Results: Among 15,569 pooled patients from 21 RCTs, colchicine was superior to placebo in the reduction of cardiovascular events. In the setting of pericardial diseases, it was associated with a lower risk of recurrent pericarditis (17 vs 34%, RR = 0.50, 95% CI: 0.42-0.60, I2 = 10%). In other studies assessing coronary artery disease patients, colchicine was associated with a reduced risk of major adverse cardiovascular events (MACE) such as myocardial infarction, stroke, cardiovascular death, coronary revascularisation and hospitalization (6.3 vs 9%, RR = 0.67, 95% CI: 0.54-0.84, I2 = 55). Among patients with atrial fibrillation, it was associated with lower rates of recurrence (20 vs 30%, RR = 0.68, 95% CI: 0.58-0.81, I2 = 0). In the single RCT on heart failure, colchicine was not associated with improved NYHA class. Conclusion: Colchicine is a valuable anti-inflammatory agent for the prevention of cardiovascular events in patients with inflammatory cardiac conditions such as pericardial diseases, coronary artery disease and atrial fibrillation.

Colchicine is an ancient drug with anti-inflammatory properties, classically used for gout and autoimmune diseases. While in the last decades it has become cornerstone for the treatment of pericarditis, in the last few years is emerging as a promising drug in the setting of coronary artery disease, heart failure and arrhythmias. Due to promising findings, almost ten trials are currently ongoing to investigate novel applications, which will be discussed throughout the paper. The aim of this systematic review and meta-analysis is to provide an overview of the latest evidence on colchicine, a microtubule-disassembling (antitubulin) agent, for the treatment and prevention of cardiovascular diseases and to discuss possible future applications.

Feasibility of an Automatic Ultrasonographic Image Acquisition System Associated With an Artificial Intelligence Algorithm for Real-Time Monitoring of Cardiac Motion During Cardiac Radio-Ablation.

Background: The management of the cardio-respiratory motion of the target and the reduction of the uncertainties related to patient's positioning are two of the main challenges that stereotactic arrhythmia radio-ablation (STAR) has to overcome. A prototype of a system was developed that can automatically acquire and interpret echocardiographic images using an artificial intelligence (AI) algorithm to calculate cardiac displacement in real-time. Methods: We conducted a single center study enrolling consecutive patients with a history of ventricular arrhythmias (VA) in order to evaluate the feasibility of this automatic acquisition system. Echocardiographic images were automatically acquired from the parasternal and apical views with a dedicated probe. The system was designed to hold the probe fixed to the chest in the supine position during both free-breathing and short expiratory breath-hold sequences, to simulate STAR treatment. The primary endpoint was the percentage of patients reaching a score ≥2 in a multi-parametric assessment evaluating the quality of automatically acquired images. Moreover, we investigated the potential impact of clinical and demographic characteristics on achieving the primary endpoint. Results: We enrolled 24 patients (63 ± 14 years, 21% females). All of them had a history of VA and 21 (88%) had an ICD. Eight patients (33%) had coronary artery disease, 12 (50%) had non-ischemic cardiomyopathy, and 3 had idiopathic VA. Parasternal, as well as apical images were obtained from all patients except from one, in whom parasternal view could not be collected due to the patient's inability to maintain the supine position. The primary endpoint was achieved in 23 patients (96%) for the apical view, in 20 patients (87%) for the parasternal view, and in all patients in at least one of the two views. The images' quality was maximal (i.e., score = 4) in at least one of the two windows in 19 patients (79%). Atrial fibrillation arrhythmia was the only clinical characteristics associated with a poor score outcome in both imaging windows (apical p = 0.022, parasternal p = 0.014). Conclusions: These results provide the proof-of-concept for the feasibility of an automatic ultrasonographic image acquisition system associated with an AI algorithm for real-time monitoring of cardiac motion in patients with a history of VA.

Efficacy and safety of colchicine for the prevention of major cardiovascular and cerebrovascular events in patients with coronary artery disease: a systematic review and meta-analysis on 12 869 patients.

AIMS: The key role of inflammation in the pathogenesis of coronary artery disease (CAD) is an urgent call for innovative treatments. Several trials have proposed colchicine as a therapeutic option for secondary prevention in CAD patients but its utilization is hampered by fears about drug-related adverse events (DAEs) and conflicting evidences. The aim of this meta-analysis was to consolidate evidence on the efficacy and safety of colchicine for secondary prevention in patients with CAD. METHODS AND RESULTS: A systematic search in electronic bibliographic databases of Medline, Scopus, Embase, and the Cochrane Library was performed to identify randomized controlled trials (RCTs) assessing the cardiovascular effects of colchicine in CAD patients, compared with placebo. Outcomes of interest were the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) and DAEs. Estimates were pooled using inverse-variance random-effects model. A total of 11 RCTs, including 12 869 patients, were identified as eligible. A total of 6501 patients received colchicine, while 6368 received placebo. After a median follow-up of 6 months (interquartile range, 1-16), patients receiving colchicine had a lower risk of MACCE [6% vs. 8.8%, relative risk (RR) = 0.67, 95% confidence interval (CI) 0.56-0.80, I2 = 19%], myocardial infarction (3.3% vs. 4.3%, RR = 0.76, 95% CI 0.61-0.96, I2 = 17%), coronary revascularization (2.9% vs. 4.2%, RR = 0.61, 95% CI 0.42-0.89, I2 = 40%), stroke (0.4% vs. 0.9%, RR = 0.48, 95% CI 0.30-0.77, I2 = 0%), hospitalization for cardiovascular cause (0.9% vs. 2.9%, RR = 0.32, 95% CI 0.12-0.87, I2 = 0%). Colchicine was associated with an increased risk of gastrointestinal DAEs (11% vs. 9.2%, RR = 1.67, 95% CI 1.20-2.34, I2 = 76%), myalgia (18% vs. 16%, RR = 1.16, 95% CI 1.02-1.32, I2 = 0%) and DAEs-related discontinuation (4.1% vs. 3%, RR = 1.54, 95% CI 1.02-2.32, I2 = 65%). However, gastrointestinal DAEs and discontinuation may be prevented with a lower daily dose. Colchicine did not increase the risk of cardiovascular death (0.7% vs. 1%, RR = 0.73, 95% CI 0.45-1.21, I2 = 14%), all-cause death (2% vs. 1.9%, RR = 1.01, 95% CI 0.71-1.43, I2 = 16%), or other DAEs. CONCLUSIONS: The use of colchicine in patients with CAD is safe and efficacious for MACCE prevention.

Validation of the ARC-HBR criteria in 68,874 patients undergoing PCI: A systematic review and meta-analysis.

The Academic Research Consortium High Bleeding Risk (ARC-HBR) criteria aims to stratify patients undergoing percutaneous coronary intervention (PCI) and are now recommended by international guidelines to stratify bleeding risk in clinical practice. We searched electronic databases from 2019 (ARC-HBR proposal) up to February 2021 for studies that reported the occurrence of major bleedings according to ARC-HBR status in patients undergoing PCI and pooled them as relative risk (RR) in a random-effect analysis. Only studies that reported events according to the number of times the ARC-HBR definition was met were included in a sensitivity analysis and RR for each stratum was calculated. Nine studies and 68,874 subjects were included in our analysis; 39.2% of them were at HBR and they had a significantly higher risk of major bleedings (RR: 2.70; 95% CI: 2.35-3.10; p < 0.0001). The ARC-HBR definition also had a moderate discriminative power (pooled c-stat: 0.69; 95% CI: 0.61-0.75) while calibration was suboptimal with a tendency toward underpredicting bleeding events (pooled observed:expected ratio: 1.47; 95% CI: 0.82-2.60). Our sensitivity analysis included 5 studies and 46,712 patients and confirmed the incremental, additive power of the ARC-HBR when it is met multiple times. Finally, among baseline characteristics explored, only presenting with an acute coronary syndrome had a significant impact on the ARC-HBR predictive ability. The ARC-HBR definition is a useful clinical tool, but with a tendency towards underpredicting major bleedings and its predictive ability might be optimized by including the number of times the definition is met.

Lipoprotein(a) Modulates Carotid Atherosclerosis in Metabolic Syndrome.

Background and Aim: High lipoprotein(a) [Lp(a)] is a well-established cardiovascular (CV) risk factor, but the effect of mildly elevated Lp(a) on CV health is largely unknown. Our aim was to evaluate if Lp(a) is associated with the severity of carotid atherosclerosis (CA) in the specific subset of metabolic syndrome (MetS). Patients and Methods: Subjects with diagnosed MetS and ultrasound-assessed CA were enrolled. Those patients were categorized according to the severity of CA (moderate vs. severe), and the circulating levels of Lp(a) alongside with clinical, anthropometric, and biochemical data were collected. Results: Sixty-five patients were finally included: twenty-five with moderate and forty with severe CA (all with asymptomatic disease). Intergroup comparison showed Lp(a) as the only significantly different variable [6 (2-12) mg/dl vs. 11.5 (6-29.5) mg/dl; p = 0.018]. Circulating levels of Lp(a) were also confirmed as the only variable independently associated with severity of CA at logistic regression analysis [OR 2.9 (95% CI 1.1-7.8); p = 0.040]. ROC curve analysis for Lp(a) confirmed a serum level of 10 mg/dl as the best cut-off value [AUC 0.675 (95% CI 0.548-0.786)]. Although sensitivity and specificity were suboptimal (69.0 and 70.4%, respectively)-likely due to the small sample size-this result is in line with those previously reported in the literature. Conclusion: Lp(a) is independently associated with severity of CA in the subgroup of MetS patients.

Post cardiac injury syndromes: diagnosis and management.

Post cardiac injury syndromes (PCIS) are becoming increasingly common, due to the growing number of cardiovascular procedures (cardiac surgery, percutaneous interventions) and the high burden of cardiovascular diseases such as acute coronary syndromes. This review aims to provide an overview of the main clinical characteristics of PCIS, along with their management in clinical practice.