Feasibility of anticoagulation on demand after percutaneous coronary intervention in high-bleeding risk patients with paroxysmal atrial fibrillation: the INTERMITTENT registry.

Aims: This study evaluated the feasibility of the intermittent use of direct oral anticoagulants (DOACs) guided by continuous rhythm monitoring via a clinically validated wearable smart device in high-bleeding risk (HBR) patients with symptomatic paroxysmal atrial fibrillation (AF) otherwise subjected to chronic anticoagulation after percutaneous coronary intervention (PCI). Methods and results: The INTERMITTENT registry was a 3-year prospective observational study at eight Italian centres. Inclusion criteria were elective or urgent PCI, Academic Research Consortium HBR criteria, history of symptomatic 12-lead ECG detected paroxysmal AF episodes, indication to DOACs, and use of a wearable smart device (Apple Watch™). Thirty days after PCI, patients free of AF episodes discontinued DOAC. However, if an AF episode lasting >6 min or a total AF burden > 6 h over 24 h was detected, DOAC was initiated for 30 consecutive days, and withdrawn afterwards if no further AF episodes occurred. At the discretion of the referring physician, intermittent anticoagulation was offered to 89 patients, whereas continuous treatment with DOACs was prescribed to 151 patients. During a follow-up of 298 ± 87 days, the average duration of oral anticoagulation was significantly shorter in the intermittent anticoagulation group (176 ± 43 days, P = 0.0001), representing a 40% reduction in anticoagulation time compared to the continuous group. Ischaemic and bleeding endpoints were not significantly different between the two groups. Propensity score-matching resulted in a total of 69 matched patients with intermittent vs. continuous anticoagulation, respectively. During a follow-up of 291 ± 63 days, there was a significant 46% reduction in anticoagulation time in the intermittent compared to the continuous group (P = 0.0001). Conclusion: In HBR patients with a history of paroxysmal AF episodes who underwent PCI, intermittent anticoagulation guided by continuous rhythm monitoring with a wearable device was feasible and decreased significantly the duration of anticoagulation.

Autologous hGMSC-Derived iPS: A New Proposal for Tissue Regeneration.

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

Rationale and Design of PURE: A Randomized Controlled Trial to Evaluate Peritoneal Ultrafiltration with PolyCore™ in Refractory Congestive Heart Failure.

INTRODUCTION: Peritoneal ultrafiltration (PUF) has been proposed as an additional therapeutic option for refractory congestive heart failure (RCHF) patients. Despite promising observational studies and/or case report results, limited clinical trial data exist, and so far, PUF solutions remain only indicated for chronic kidney diseases. In this article, we described a multicenter, randomized, controlled, unblinded, adaptive design clinical trial, about to start, investigating the effects of PolyCore™, an innovative PUF solution, in the treatment of RCHF patients. METHODS: The Peritoneal Ultrafiltration in Cardiorenal Syndrome (PURE) study is a phase II, multicenter, randomized, controlled, unblinded, adaptive design clinical trial that aims to evaluate the safety and efficacy of PUF, using PolyCore™ as the investigational solution, in the treatment of RCHF patients who present with prominent right ventricular failure due to afterload mismatch, functional tricuspid regurgitation and enlarged cava vein consequent to intravascular fluid overload. Approximately 84 patients will be randomized 1:1 either to continue with their prescribed guideline-directed medical therapy or to add the PUF treatment on top of it. The primary objective is to evaluate if PUF treatment has an impact on the composite endpoint of the patient's mortality or worsening of the patient's condition such as hospitalization for cardiovascular causes, increasing the initial daily dose of loop diuretic or worsening of renal function. Statistical analysis for the primary endpoint will be standard survival analysis to estimate the failure rate at month 7 for each group via Kaplan-Meier curves. Sensitivity analysis and various secondary analyses, including a multiple events analysis, will be conducted to evaluate the robustness of the primary endpoint results. Safety will be evaluated for up to 12 months. CONCLUSION: The PURE study was designed to evaluate the safety and efficacy of peritoneal ultrafiltration with PolyCore™ on top of guideline-directed medical therapy in patients with RCHF, assuming a combined clinical endpoint of mortality or worsening patients' condition. If successful, the treatment should allow for an improvement of the RCHF symptoms, decreasing hospitalization rate of patients.

Red Blood Cell Transfusion Strategies in Cardiovascular Interventions.

Acute coronary syndrome, cardiac surgery, and cardiac structural interventions are among the most common situations leading to allogeneic red blood cell consumption due to the prevalence of bleeding and anemia. The wide variability in the use of transfusions derives from the current lack of data, and the absence of strong evidence and clear guideline recommendations. The current approach is to avoid unnecessary blood transfusions and limit their use to life-saving conditions; this conservative strategy derives from often controversial and inconclusive results of observational and randomized studies where liberal and restricted red blood transfusion strategies seemed to have similar outcomes. The pivotal question for future research lies in elucidating whether blood transfusions function as an active participant or merely a catalyst in amplifying adverse events. The present review aims to summarize the current literature data and critically analyze the available evidence for red blood transfusions in cardiac interventions.

Biomechanical factors and atherosclerosis localization: insights and clinical applications.

Although the entire vascular bed is constantly exposed to the same risk factors, atherosclerosis manifests a distinct intra-individual pattern in localization and progression within the arterial vascular bed. Despite shared risk factors, the development of atherosclerotic plaques is influenced by physical principles, anatomic variations, metabolic functions, and genetic pathways. Biomechanical factors, particularly wall shear stress (WSS), play a crucial role in atherosclerosis and both low and high WSS are associated with plaque progression and heightened vulnerability. Low and oscillatory WSS contribute to plaque growth and arterial remodeling, while high WSS promotes vulnerable changes in obstructive coronary plaques. Axial plaque stress and plaque structural stress are proposed as biomechanical indicators of plaque vulnerability, representing hemodynamic stress on stenotic lesions and localized stress within growing plaques, respectively. Advancements in imaging and computational fluid dynamics techniques enable a comprehensive analysis of morphological and hemodynamic properties of atherosclerotic lesions and their role in plaque localization, evolution, and vulnerability. Understanding the impact of mechanical forces on blood vessels holds the potential for developing shear-regulated drugs, improving diagnostics, and informing clinical decision-making in coronary atherosclerosis management. Additionally, Computation Fluid Dynamic (CFD) finds clinical applications in comprehending stent-vessel dynamics, complexities of coronary bifurcations, and guiding assessments of coronary lesion severity. This review underscores the clinical significance of an integrated approach, concentrating on systemic, hemodynamic, and biomechanical factors in atherosclerosis and plaque vulnerability among patients with coronary artery disease.

Optimizing Management of Stable Angina: A Patient-Centered Approach Integrating Revascularization, Medical Therapy, and Lifestyle Interventions.

Angina pectoris may arise from obstructive coronary artery disease (CAD) or in the absence of significant CAD (ischemia with nonobstructed coronary arteries [INOCA]). Therapeutic strategies for patients with angina and obstructive CAD focus on reducing cardiovascular events and relieving symptoms, whereas in INOCA the focus shifts toward managing functional alterations of the coronary circulation. In obstructive CAD, coronary revascularization might improve angina status, although a significant percentage of patients present angina persistence or recurrence, suggesting the presence of functional mechanisms along with epicardial CAD. In patients with INOCA, performing a precise endotype diagnosis is crucial to allow a tailored therapy targeted toward the specific pathogenic mechanism. In this expert opinion paper, we review the evidence for the management of angina, highlighting the complementary role of coronary revascularization, optimal medical therapy, and lifestyle interventions and underscoring the importance of a personalized approach that targets the underlying pathobiology.

Red blood cell transfusion and mortality after transcatheter aortic valve implantation via transapical approach: A propensity-matched comparison from the TRITAVI registry.

Objective: Bleeding is frequent during transcatheter aortic valve implantation (TAVI), especially when performed through a transapical approach (TA), and is associated with a worse prognosis. The present study aims to test the implication of red blood cell (RBC) transfusion and the optimal transfusion strategy in this context. Methods: Among 11,265 participants in the multicenter TRITAVI (Transfusion Requirements in Transcatheter Aortic Valve Implantation) registry, 548 patients (4.9%) who received TA-TAVI at 19 European centers were included. One-to-one propensity score matching was performed to reduce treatment selection bias and potential confounding among transfused versus non-transfused patients. The primary endpoint of the study was the 30-day occurrence of all-cause mortality. Results: 209 patients (38 %) received RBC transfusions. The primary endpoint occurred in 47 (8.6 %) patients. Propensity score matching identified 188 pairs of patients with and without RBC transfusion. In the propensity score-matched analysis, RBC transfusion was associated with increased 30-day mortality (HR 3.35, 95 % CI 1.51 - 7.39; p = 0.002). At multivariable cox regression analysis, RBC transfusion was an independent predictor of 30-day mortality (HR 3.07, 95 % CI 1.01-9.41, p = 0.048), as well as baseline ejection fraction (HR 0.96, 95 % CI 0.92-0.99, p = 0.043), and acute kidney injury (HR 3.95, 95 % CI 1.11-14.05, p = 0.034). Conclusions: RBC transfusion is an independent predictor of short-term mortality in patients undergoing TA-TAVI, regardless of major bleeding.Clinical trial registration: https://www.clinicaltrials.gov Unique identifier: NCT03740425.

Therapeutic strategies aiming at the reduction of the antiplatelet intensity should not overlook the ischemic risk in patients with coronary syndromes.

De-escalation of dual antiplatelet therapy (DAPT) is gaining traction as a strategy to reduce bleeding risks while ensuring ischemic outcomes. Undiscriminating de-escalation, notably in patients with high ischemic risk, might expose them to major adverse cardiac events. Platelet function and genetic tests are emerging tools to guide de-escalation, but both present specific drawbacks. Recent meta-analyses have aimed to consolidate the findings of individual trials to provide clearer insights. Yet, limitations remain for patients with concomitant high bleeding and ischemic risks. These high-risk patients are frequently underrepresented in clinical trials, and, therefore, currently available guidelines lack evidence-based recommendations for this subset. While DAPT de-escalation strategies hold promise, the choice of approach, whether clinically or assay-guided, remains complex and should be individualized.

Risk Score for Prediction of Dialysis After Transcatheter Aortic Valve Replacement.

BACKGROUND: Dialysis is a rare but serious complication after transcatheter aortic valve replacement. We analyzed the large multicenter TRITAVI (transfusion requirements in transcatheter aortic valve implantation) registry in order to develop and validate a clinical score assessing this risk. METHODS AND RESULTS: A total of 10 071 consecutive patients were enrolled in 19 European centers. Patients were randomly assigned (2:1) to a derivation and validation cohort. Two scores were developed, 1 including only preprocedural variables (TRITAVIpre) and 1 also including procedural variables (TRITAVIpost). In the 6714 patients of the derivation cohort (age 82±6 years, 48% men), preprocedural factors independently associated with dialysis and included in the TRITAVIpre score were male sex, diabetes, prior coronary artery bypass graft, anemia, nonfemoral access, and creatinine clearance <30 mL/min per m2. Additional independent predictors among procedural features were volume of contrast, need for transfusion, and major vascular complications. Both scores showed a good discrimination power for identifying risk for dialysis with C-statistic 0.78 for TRITAVIpre and C-statistic 0.88 for TRITAVIpost score. Need for dialysis increased from the lowest to the highest of 3 risk score groups (from 0.3% to 3.9% for TRITAVIpre score and from 0.1% to 6.2% for TRITAVIpost score). Analysis of the 3357 patients of the validation cohort (age 82±7 years, 48% men) confirmed the good discrimination power of both scores (C-statistic 0.80 for TRITAVIpre and 0.81 for TRITAVIpost score). Need for dialysis was associated with a significant increase in 1-year mortality (from 6.9% to 54.4%; P=0.0001). CONCLUSIONS: A simple preprocedural clinical score can help predict the risk of dialysis after transcatheter aortic valve replacement.

Reproducibility of an artificial intelligence optical coherence tomography software for tissue characterization: Implications for the design of longitudinal studies.

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