A multicenter prospective observational study appraising the effectiveness of the Supera stent after subintimal recanalization of femoro-popliteal artery occlusion: The SUPERSUB II study.

BACKGROUND: Complex femoropopliteal artery disease represents a challenge. The Supera stent holds the promise of improving the results of endovascular therapy for complex femoropopliteal disease. AIMS: We aimed at appraising the early and long-term effectiveness of the Supera stent after successful subintimal angioplasty (SuperSUB strategy) for complex femoropopliteal lesions. METHODS: We conducted a multicenter, prospective, single-arm observational study including consecutive patients at participating centers in whom Supera was implanted after successful subintimal angioplasty for complex femoropopliteal lesions. RESULTS: A total of 92 patients were included Femoropopliteal arteries were the most common target, and lesion length was 261 ± 102 mm. Most procedures were technically demanding, with antegrade femoral access in 35 (38%) and retrograde distal access in 55 (60%). Supera stent length was 281 ± 111 mm, with 4, 5, and 6 mm devices being most commonly used: 32 (35%), 35 (38%), and 23 (25%), respectively. Technical success was achieved in 100% of subjects, as was clinical success (per subject), whereas procedural success (per subject) was obtained in 98%. At 24 months, freedom from clinically driven target lesion revascularization was 93%, whereas primary patency was 87%. When compared with a similar historical cohort, Supera stent use appeared to be associated with a reduction in resources. CONCLUSION: Use of Supera stent after successful subintimal recanalization of complex lower limb arterial lesions yields favorable procedural results, which are maintained over follow-up, and are associated also with a favorable resource use profile.

Transcatheter mitral valve repair with MitraClip: comparison of NT, NTr, and XTr Devices.

OBJECTIVES: Transcatheter edge-to-edge repair (TEER) has become an established minimally invasive treatment for significant mitral regurgitation. Ongoing refinements and the availability of different clipping devices have expanded the indications for and effectiveness of TEER, but comprehensive comparative data on this issue are lacking. In this study, we compared NT, NTr, and XTr MitraClip devices (Abbot) for TEER. METHODS: Details on patient, imaging, and procedural details, as well as short- and long-term outcomes, were sought from a national prospective clinical registry on TEER with MitraClip. The primary outcome of interest was discharge after procedural success without major clinical complications. RESULTS: A total of 2236 patients were included, 1228 (54.9%) in whom NT implantation only was attempted, 233 (10.4%) in whom NTr but not XTr implantation was attempted, and 775 (34.7%) in whom XTr implantation was attempted. Clinical and imaging features differed substantially across the groups, reflecting expanding indications with NTr and XTr devices. In-hospital outcomes were largely similar among the 3 groups, including death. Long-term unadjusted estimates of effect showed significant differences in several outcomes, including death, rehospitalization, and their composite, which demonstrated that NT was associated with more unfavorable outcomes compared with the other devices (all P less than .05). However, most differences depended on baseline features, as adjusted analysis showed no significant differences for early as well as long-term outcomes, including long-term death, rehospitalization, and their composite (all P greater than .05). CONCLUSIONS: New-generation MitraClip devices are associated with favorable procedural and clinical outcomes, despite being used in patients with more adverse features, when compared with patients treated with previous devices.

Statistical primer: individual patient data meta-analysis and meta-analytic approaches in case of non-proportional hazards.

Individual patient data (IPD) meta-analyses build upon traditional (aggregate data) meta-analyses by collecting IPD from the individual studies rather than using aggregated summary data. Although both traditional and IPD meta-analyses produce a summary effect estimate, IPD meta-analyses allow for the analysis of data to be performed as a single dataset. This allows for standardization of exposure, outcomes, and analytic methods across individual studies. IPD meta-analyses also allow the utilization of statistical methods typically used in cohort studies, such as multivariable regression, survival analysis, propensity score matching, uniform subgroup and sensitivity analyses, better management of missing data, and incorporation of unpublished data. However, they are more time-intensive, costly, and subject to participation bias. A separate issue relates to the meta-analytic challenges when the proportional hazards assumption is violated. In these instances, alternative methods of reporting time-to-event estimates, such as restricted mean survival time should be used. This statistical primer summarizes key concepts in both scenarios and provides pertinent examples.

Comparative diagnostic accuracy of transcranial Doppler and contrast-enhanced transthoracic echocardiography for the diagnosis of patent foramen ovale and atrial septal defect.

BACKGROUND: Recognition of right-to-left shunt is crucial in the work-up of patients with suspected patent foramen ovale (PFO) or atrial septal defect (ASD). While transesophageal echocardiography (TEE) remains the gold standard diagnostic tool for the anatomic assessment of PFO/ASD, transcranial Doppler (TCD) and contrast-enhanced transthoracic echocardiogram (CE-TTE) hold the promise of providing minimally invasive yet accurate clinical details. Their comparative accuracy remains however debated. METHODS: We conducted a retrospective observational study leveraging our extensive institutional experience with systematic TCD and CE-TTE in patients with suspected PFO/ASD. Several measures of diagnostic test accuracy were computed, with point estimates and 95% confidence intervals, when applicable. RESULTS: A total of 1358 patients were included, with age 48±14 years and 772 (58%) women. Tests were performed for diagnostic purposes in 797 (58.6%) and during follow-up in 740 (54.5%). A PFO was eventually diagnosed in 1038 (77.9%) patients, and an ASD in 60 (4.5%). Agreement between TCD and CE-TTE occurred in 1309 (85.2%) cases, with TCD yielding worse findings than CE-TTE in 91 (5.9%) patients, and vice versa in 137 (8.9%), yielding a Cohen kappa of 78.6% (95% CI: 76.3-81.1%) and a highly significant P value at McNemar test (P<0.001). After dichotomization, and using TCD as benchmark, CE-TTE yielded sensitivity 96.9%, specificity 95.1%, area under the curve 92.1%, and P=0.249. Similar findings were obtained when focusing only on diagnostic tests or follow-up ones (Cohen kappa respectively 74.0% [70.2-77.1%], P<0.001 and 80.3% [76.4-84.3%], P<0.001). Notably, Valsalva was necessary to disclose the presence of shunt during TCD in 487 (31.7%) patients and during CE-TTE in 482 (31.4%) cases. Finally, performance of TCD and CE-TTE in a subset of patients eventually undergoing TTE was quite similar. CONCLUSIONS: The diagnostic accuracy of CE-TTE appears favorable, and this imaging test may identify patients who may be missed if only TCD is used to screen patients with suspected PFO/ASD. Accordingly, CE-TTE is recommended as an adjunct diagnostic modality for all patients with a high pre-test probability of PFO/ASD and right-to-left shunt.

Intraprocedural continuous saline infusion lines significantly reduce the incidence of acute kidney injury during endovascular procedures for stroke and myocardial infarction: evidence from a systematic review and meta-regression.

BACKGROUND: Contrast media used in mechanical therapies for stroke and myocardial infarction represent a significant cause of acute kidney injury (AKI) in acute medical scenarios. Although the continuous saline infusion line (CSIL) is a standard procedure to prevent thrombus formation within the catheter during neurovascular interventions of mechanical thrombectomy (MT), it is not utilized in percutaneous coronary interventions (PCI). METHODS: A systematic review of the incidence of AKI after MT for stroke treatment was performed. These data were compared with those reported in the literature regarding the incidence of AKI after PCI for acute myocardial infarction. A random-effect model meta-regression was performed to explore the effects of CSIL on AKI incidence, using clinical details as covariates. RESULTS: A total of 18 and 33 studies on MT and PCI were included, respectively, with 69,464 patients (30,138 [43.4%] for MT and 39,326 [56.6%] for PCI). The mean age was 63.6 years±5.8 with male 66.6%±12.8. Chronic kidney disease ranged 2.0-50.3%. Diabetes prevalence spanned 11.1% to 53.0%. Smoking status had a prevalence of 7.5-72.0%. Incidence of AKI proved highly variable (I2=98%, Cochrane's Q 2985), and appeared significantly lower in the MT subgroup than in the PCI subgroups (respectively 8.3% [95% confidence interval: 4.7-11.9%] vs. 14.7 [12.6-16.8%], P<0.05). Meta-regression showed that CSIL was significantly associated with a decreased incidence of AKI (OR=0.93 [1.001-1.16]; P=0.03). CONCLUSIONS: Implementation of CSIL during endovascular procedures in acute settings was associated with a significant decrease in the risk of AKI, and its safety should be routinely considered in such interventions.

Acute and long-term results of percutaneous coronary intervention of bifurcation lesions with the dedicated Bioss Lim C stent: the Italian BIfurcation Observational Spontaneous Study (IBIOSS).

BACKGROUND: Percutaneous coronary intervention (PCI) for bifurcation lesions still represents a clinical challenge. The Bioss Lim C is a dedicated device for bifurcation lesions, features a tapered shape and large cells, and thus appears as a promising adjunct to the current interventional cardiologists' armamentarium. We aimed at conducting a prospective multicenter study focusing on early and long-term results after Bioss Lim C implantation for true coronary bifurcation lesions. METHODS: Patients with true bifurcation lesions in whom Bioss Lim C implantation was attempted were enrolled in four Italian centers. An explicit bifurcation management approach was recommended, leaving however the choice between one- vs. two-stent strategies at operator's discretion. Acute and long-term results were systematically appraised, focusing on an acute composite of complex side branch (SB) rewiring, SB pinching, or SB occlusion (primary efficacy endpoint), as well as major adverse events (MACE, i.e. death, myocardial infarction [MI], or target vessel revascularization [TVR]), individual components of MACE, and stent thrombosis. RESULTS: A total of 207 patients were included, with age of 67.3±10.8 years, and 40 (19.3%) women. The target lesion was located in the left main in 48 (23.2%) patients, whereas proximal reference vessel diameter was 3.69±0.48 mm, and lesion length 20.3±3.4 mm. According to the Medina classification, most patients (60 [30.9%]) had 1-1-1 lesions. Drug-eluting stent implantation in the SB was carried out in 19 (9.3%) subjects, and kissing balloon inflation was used in 67 (32.5%). The primary efficacy endpoint occurred in 27 (13.0%), with side branch (SB) occlusion in two (1.0%), SB pinching in 23 (11.1%), and complex SB rewiring in six (2.9%), and was most frequent in patients with lower body mass index or dyslipidemia. After 24.1±19.5 months, MACE were adjudicated in 23 (11.1%) subjects, with death in 10 (4.8%), MI in six (2.9%), and TVR in seven (3.4%), as well as stent thrombosis in one (0.5%). CONCLUSIONS: This study supports a wider adoption of the Bioss Lim C dedicated bifurcation device, thanks to the favorable acute results as well as long-term clinical outcomes, as well as its versatility for the stenting strategy provisionally or eventually adopted by operators.

European Association of Cardio-Thoracic Surgery (EACTS) expert consensus statement on perioperative myocardial infarction after cardiac surgery.

Cardiac surgery may lead to myocardial damage and release of cardiac biomarkers through various mechanisms such as cardiac manipulation, systemic inflammation, myocardial hypoxia, cardioplegic arrest and ischaemia caused by coronary or graft occlusion. Defining perioperative myocardial infarction (PMI) after cardiac surgery presents challenges, and the association between the current PMI definitions and postoperative outcomes remains uncertain. To address these challenges, the European Association of Cardio-Thoracic Surgery (EACTS) facilitated collaboration among a multidisciplinary group to evaluate the existing evidence on the mechanisms, diagnosis and prognostic implications of PMI after cardiac surgery. The review found that the postoperative troponin value thresholds associated with an increased risk of mortality are markedly higher than those proposed by all the current definitions of PMI. Additionally, it was found that large postoperative increases in cardiac biomarkers are prognostically relevant even in absence of additional supportive signs of ischaemia. A new algorithm for PMI detection after cardiac surgery was also proposed, and a consensus was reached within the group that establishing a prognostically relevant definition of PMI is critically needed in the cardiovascular field and that PMI should be included in the primary composite outcome of coronary intervention trials.

Exploring the Promise and Challenges of Artificial Intelligence in Biomedical Research and Clinical Practice.

Artificial intelligence (AI) is poised to revolutionize how science, and biomedical research in particular, are done. With AI, problem solving and complex tasks using massive data sets can be performed at a much higher rate and dimensionality level compared to humans. With the ability to handle huge data sets and self-learn, AI is already being exploited in drug design, drug repurposing, toxicology, and material identification. AI could also be used in both basic and clinical research in study design, defining outcomes, analyzing data, interpreting findings, and even identifying the most appropriate areas of investigation and funding sources. State-of-the-art AI-based large language models (LLM), such as ChatGPT and Perplexity, are positioned to change forever how science is communicated and how scientists interact with one another and their profession, including post-publication appraisal and critique. Like all revolutions, upheaval will follow and not all outcomes can be predicted, necessitating guardrails at the onset, especially to minimize the untoward impact of the many drawbacks of LLMs, which include lack of confidentiality, risk of hallucinations, and propagation of mainstream albeit potentially mistaken opinions and perspectives. In this review, we highlight areas of biomedical research that are already being reshaped by AI and how AI is likely to impact it further in the near future. We discuss the potential benefits of AI in biomedical research and address possible risks, some surrounding the creative process, that warrant further reflection.

Atherosclerotic Plaque Erosion: Mechanisms, Clinical Implications, and potential therapeutic Strategies - a review.

Atherosclerosis is an insidious and progressive inflammatory disease characterized by the formation of lipid-laden plaques within the intima of arterial walls with potentially devastating consequences. While rupture of vulnerable plaques has been extensively studied, a distinct mechanism known as plaque erosion has gained recognition and attention in recent years. Plaque erosion, characterized by the loss of endothelial cell lining in the presence of intact fibrous cap contributes to a significant and growing proportion of acute coronary events. However, despite a heterogenous substrate underlying coronary thrombosis, treatment remains identical. This article provides an overview of atherosclerotic plaque erosion characteristics and its underlying mechanisms, highlights its clinical implications, and discusses potential therapeutic strategies.

Cardiovascular disease as part of Long COVID: A systematic review.

BACKGROUND: Long COVID syndrome has had a major impact on million patients' lives worldwide. The cardiovascular system is an important aspect of this multifaceted disease that may manifest in many ways. We have hereby performed a narrative review in order to identify the extent of the cardiovascular manifestations of the Long COVID syndrome. METHODS AND RESULTS: An in-depth systematic search of the literature has been conducted for this narrative review. The systematic search of PubMed and Cochrane databases yielded 3,993, of which 629 underwent full text screening. A total of 78 studies were included in the final qualitative synthesis and data evaluation. The pathophysiology of the cardiovascular sequelae of Long COVID syndrome and the cardiac manifestations and complications of Long COVID syndrome are critically evaluated. In addition, potential cardiovascular risk factors are assessed, and preventive methods and treatment options are examined in this review. CONCLUSIONS: This systematic review poignantly summarises the evidence from the available literature regarding the cardiovascular manifestations of Long COVID syndrome and reviews potential mechanistic pathways, diagnostic approaches, preventive measures and treatment options.

Impact of heat-not-burn cigarette passive smoking on children's oxidative stress, endothelial and platelet function.

Growing global use of heat-not-burn cigarettes (HNBC) prompts investigation. Prior studies assessed HNBC's effects on cardiovascular health, revealing heightened oxidative stress, platelet activation, and endothelial dysfunction. However, limited understanding exists regarding passive smoking's impact on children exposed to HNBC. This study aims to assess levels of oxidative stress, endothelial and platelet function among children exposed to passive smoke from HNBC, traditional tobacco (TT) cigarettes and unexposed subjects. Seventy-eight children (2-18 years) were divided into three groups: HNBC passive smokers (n = 26), TT cigarette exposed (n = 26), and control (CNT) group (n = 26, unexposed). Oxidative stress was evaluated by serum NADPH oxidase-2 (NOX2) activity, assessed by soluble Nox2-derived peptide (sNOX2-dp), isoprostanes, hydrogen peroxide (H2O2) production, hydrogen break-down activity (HBA) and NO bioavailability. Endothelial function was assessed by brachial flow-mediated dilation (FMD). Platelet function was evaluated by soluble CD40 ligand (sCD40L), soluble P-selectin (sP-selectin) and thrombus formation by T-TAS analysis. Passive smoking-exposed children (both HNBC and TT) exhibited significantly increased serum sNOX2-dp, isoprostanes, H2O2, sCD40L sP-selectin and thrombus formation versus controls. Conversely, exposed children displayed reduced brachial FMD and serum NO bioavailability. No significant differences were found between children exposed to passive smoking of HNBC vs TT. Multivariable regression linked sNOX2 (standardized coefficient ß: 0.284; SE: 0.040; p = 0.01) and H2O2 (standardized coefficient ß: 0.243; SE: 0.0; p = 0.02) as independent predictors of FMD, and isoprostanes (standardized coefficient ß:0.388; SE: 0.022; p < 0.001) and serum cotinine (standardized coefficient ß:0.270; SE: 0.048; p = 0.01) with sNOX2-dp levels. Exposure to HNBC smoke heightened oxidative stress, endothelial dysfunction, platelet activation, and thrombus formation in children. Findings suggest avenues for interventions to curb childhood passive smoking exposure.

Lorcaserin: Worthy of Further Insights? Results from Recent Research.

Lorcaserin is a 3-benzazepine that binds 5-HT2C serotonin receptors in the hypothalamus, where it mediates lack of hunger and/or satiety, and in the ventral tegmental area, the site of origin of the mesolimbic and mesocortical dopaminergic projections, which mediate pleasure and reward. The drug has been first developed for the treatment of obesity, where it has shown efficacy, and subsequently trialed to counter substance use (mostly cocaine, cannabis, opioids, and nicotine) and craving, but showed inconsistent effects. Since 2020, the US Food and Drug Administration obtained that the drug was voluntarily withdrawn from the US market on the grounds that its long-term use was found to be associated with a greater incidence of some types of cancer. Provided it can show to be free from cancerogenic effects, ongoing research suggests that lorcaserin may have therapeutic potential for a variety of disorders and conditions beyond obesity. Since 5-HT2C receptors are involved in many diversified physiological functions (mood, feeding, reproductive behavior, neuronal processes related to impulsiveness, and modulating reward-related mechanisms) this drug has the potential to treat different central nervous system conditions, such as depression and schizophrenia.

Does PM 2.5 and PM 10-associated heavy metals affect short-term and long-term survival after out-of-hospital cardiac arrest? Four-year study based on regional registry.

BACKGROUND: This study aims to investigate the effect of arsenic (As), cadmium (Cd), nickel (Ni) and lead (Pb) suspended on particulate matters (PM) 2.5 and PM 10 taking into account clinical factors on 30-day and one-year survival after out-of-hospital cardiac arrest (OHCA). METHODS: A retrospective 4-year study that involved patients hospitalized after OHCA. Patients' data were obtained from Emergency Medical Services dispatch cards and the National Health Fund. The concentration of air pollutants was measured by the Environmental Protection Inspectorate in Poland. RESULTS: Among the 948 patients after OHCA, only 225 (23.7%) survived for 30 days, and 153 (16.1%) survived for 1 year. Survivors were more commonly affected by OHCA in urban areas (85 [55.6%] vs. 355 [44.7%]; P=0.013) and had slightly higher one-year mean concentration of As (0.78 vs. 0.77; P=0.01), Cd (0.34 vs. 0.34; P=0.012), and Pb (11.13 vs. 10.20; P=0.015) with no differences in daily mean concentration. Significant differences in mean concentrations of heavy metals and PM 2.5 and PM 10 were observed among different quarters. However, survival analysis revealed no differences in long-term survival between quarters. Heavy metals, PM 2.5, and PM 10 did not affect short-term and long-term survival in multivariable logistic regression. CONCLUSIONS: The group of survivors showed slightly higher mean one-year concentrations of As, Cd and Pb, but they also experienced a higher incidence of OHCA in urban areas. There were no differences in long-term survival between patients who suffer OHCA in different quarters. Heavy metals did not independently affect survival.