Inclisiran: present and future perspectives of a new effective LDL cholesterol-lowering agent.

PURPOSE OF REVIEW: To highlight critical aspects of inclisiran, from preclinical studies to current recommendations in clinical practice and future perspectives. RECENT FINDINGS: Inclisiran use has been recently approved by regulatory agencies. The evidence of its efficacy and safety makes it a promising therapeutical tool for treating dyslipidemias. SUMMARY: The link between LDL-cholesterol and atherosclerotic cardiovascular disease (ASCVD) is well established. Inclisiran, a small interfering RNA, has proven its safety and efficacy in reducing LDL-cholesterol, and FDA and EMA have recently approved its use. This review illustrates the development, structure, and mechanism of action of inclisiran and provides information regarding its efficacy, safety, and current recommendation in clinical practice. Moreover, it provides key information on the most recent/ongoing trials that will help us to implement the use of inclisiran in clinical practice.

The effects of platelet-rich plasma injections in different stages of knee osteoarthritis.

PURPOSE: Platelet-rich plasma (PRP) injections are challenging the current treatment options for knee osteoarthritis (KOA). Targeting the treatment to optimal stage of the symptomatic KOA may be crucial in the success and failure of treatment. The aim of this study is to compare the outcomes of PRP injections at different stages of KOA in order to determine the optimal stage of the KOA for PRP injection treatments. METHODS: A total of 89 consecutive patients with symptomatic KOA Kellgren-Lawrence grade 1 to 3 (Group A grade 1, group B grade 2 and group C grade 3) were given three intra-articular injections of PRP with 2 weeks interval between injections. Visual Analogue Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Range of Motion were measured before injection, at 15 days, 6 months, 12 months and, at last follow-up. Intergroup outcomes were compared. RESULTS: The comparison of groups A and C showed that WOMAC scores were significantly higher in group C at 15 days [p = 0.047] and at last follow-up [p = 0.008] than in group A, as well as VAS scores at 6 months [p = 0.031] and at last follow-up [p = 0.008]. The overall WOMAC and VAS scores showed decrease in all the groups in minimum follow-up of 14 months. The other comparisons did not show significant differences in outcomes. CONCLUSION: All the groups showed decrease in WOMAC and VAS, but patients with mild KOA benefit significantly more from the treatments than patients with more severe KOA.

Transcatheter aortic valve implantation with the novel-generation Navitor device: Procedural and early outcomes.

Transcatheter aortic valve implantation (TAVI) has proved beneficial in patients with severe aortic stenosis, especially when second-generation devices are used. We aimed at reporting our experience with Navitor, a third-generation device characterized by intrannular, large cell, and cuffed design, as well as high deliverability and minimization of paravalvular leak. Between June and December 2021, a total of 39 patients underwent TAVI with Navitor, representing 20% of all TAVI cases. Mean age was 80.0 ± 6.7 years, and 14 (36.8%) women were included. Severe aortic stenosis was the most common indication to TAVI (37 [97.4%] cases), whereas 2 (5.3%) individuals were at low surgical risk. Device and procedural success was obtained in all patients, with a total hospital stay of 6.6 ± 4.5 days. One (2.9%) patient required permanent pacemaker implantation, but no other hospital events occurred. At 1-month follow-up, a cardiac death was adjudicated in an 87-year-old man who had been at high surgical risk. Echocardiographic follow-up showed no case of moderate or severe aortic regurgitation, with mild regurgitation in 18 (47%), and none or trace regurgitation in 20 (53%). The Navitor device, thanks to its unique features, is a very promising technology suitable to further expand indications and risk-benefit profile of TAVI.

Synthetic Mesh Versus Acellular Dermal Matrix for Oncologic Chest Wall Reconstruction: A Comparative Analysis.

BACKGROUND: Management of chest wall defects after oncologic resection is challenging due to multifactorial etiologies. Traditionally, skeletal stabilization in chest wall reconstruction (CWR) was performed with synthetic prosthetic mesh. The authors hypothesized that CWR for oncologic resection defects with acellular dermal matrix (ADM) is associated with a lower incidence of complications than synthetic mesh. METHODS: Consecutive patients who underwent CWR using synthetic mesh (SM) or ADM at a single center were reviewed. Only oncologic defects involving resection of at least one rib and reconstruction with both mesh and overlying soft tissue flaps were included in this study. Patients' demographics, treatment factors, and outcomes were prospectively documented. The primary outcome measure was surgical-site complications (SSCs). The secondary outcomes were specific wound-healing events, cardiopulmonary complications, reoperation, and mortality. RESULTS: This study investigated 146 patients [95 (65.1%) with SM; 51 (34.9%) with ADM] who underwent resection and CWR of oncologic defects. The mean follow-up period was 29.3 months (range 6-109 months). The mean age was 51.5 years, and the mean size of the defect area was 173.8 cm2. The SM-CWR patients had a greater number of ribs resected (2.7 vs. 2.0 ribs; p = 0.006) but a similar incidence of sternal resections (29.5% vs. 23.5%; p = 0.591) compared with the ADM-CWR patients. The SM-CWR patients experienced significantly more SSCs (32.6% vs. 15.7%; p = 0.027) than the ADM-CWR patients. The two groups had similar rates of specific wound-healing complications. No differences in mortality or reoperations were observed. CONCLUSIONS: The ADM-CWR patients experienced fewer SSCs than the SM-CWR patients. Surgeons should consider selectively using ADM for CWR, particularly in patients at higher risk for SSCs.

Horizontal animation deformity as unusual complication of neurotoxin modulation of the gummy smile.

Injections of botulinum toxin type A represent the most common nonsurgical cosmetic treatment worldwide. The authors report a case of dynamic horizontal wrinkling in the upper lip that appeared after botulinum toxin type A injections to treat gummy smile associated with nasal alar base reduction, in a 28-year-old woman. The anatomic features and pathogenic mechanism underlying this unusual complication are analyzed and discussed.

Prior Radiotherapy Does Not Affect Abdominal Wall Reconstruction Outcomes: Evidence from Propensity Score Analysis.

BACKGROUND: Prior abdominal wall radiotherapy (XRT) adversely affects wound healing, but data are limited on how prior XRT may affect abdominal wall reconstruction (AWR) outcomes. The purpose of this study was to determine whether prior abdominal wall radiotherapy is associated with a higher incidence of complications following AWR for a hernia or oncologic resection defect. METHODS: We performed a retrospective study of consecutive patients who underwent complex AWR using acellular dermal matrix (ADM) at a single center. We compared outcomes between patients who underwent prior XRT that directly involved the abdominal wall and those who did not receive XRT. Propensity score match-paired and multivariate analyses were performed. RESULTS: A total of 511 patients (130 [25.4 %] with prior XRT; 381 [74.6 %] without prior XRT) underwent AWR with ADM for repair of a complex hernia or oncologic resection defect. Mean follow-up was 31.4 months, mean XRT dose was 48.9 Gy, and mean time between XRT and reconstruction was 19.2 months. XRT AWR patients underwent more flap reconstructions (14.6 vs. 5.0 %, P < 0.001) but fewer component separations (61.5 vs. 71.4 %; P = 0.036) than non-XRT AWR patients. The two groups had similar rates of hernia recurrence (8.5 vs. 9.4 %; P = 0.737) and surgical site occurrence (25.4 vs. 23.4 %; P = 0.640). In the propensity score-matched subgroups, there were no differences in hernia recurrence, surgical site occurrence, and wound healing complication rates. CONCLUSIONS: Prior XRT does not adversely affect outcomes in AWR. However, surgeons should be aware of the higher likelihood of needing a soft tissue flap reconstruction for soft tissue replacement when performing AWR after XRT.

One-cm Versus 2-cm Excision Margins for Patients With Intermediate Thickness Melanoma: A Matched-Pair Analysis.

BACKGROUND: Optimum excision margins used in the removal of intermediate thickness melanomas remain unclear. OBJECTIVE: This study's aim was to compare the clinical outcomes of 1-cm margins with 2-cm margins in patients with a tumor thickness of 1.1- to 4.0-mm. MATERIALS AND METHODS: This was a retrospective study, which was based on a matched-pairs design. Equal patient cohorts were constructed in terms of gender, age, Breslow thickness, and the anatomic location of the primary lesion. There were 80 patients whom underwent an excision with a 1-cm margin and 80 patients with a 2-cm margin. Follow-up data were analyzed by the Kaplan-Meier method and a Cox regression model. RESULTS: After a median follow-up time of 41 months, there were no differences in relapse-free survival or melanoma-specific survival between study groups. The wound was closed directly in 62 patients (78%) in the 1-cm group and in 36 patients (45%) in the 2-cm group (p < .001). CONCLUSION: A 1-cm excision margin may be sufficient in melanomas of 1.1 to 2.0 mm in Breslow thickness based on these findings of low recurrence. With thicker tumors (2.1-4.0 mm), this recommendation cannot be given due to inherent study limitations.

Laparoscopic Roux-en-Y gastric bypass is effective and safe in over 55-year-old patients: a comparative analysis.

BACKGROUND: Controversy exists regarding the effectiveness and safety of laparoscopic Roux-en-Y gastric bypass (LRYGB) in elderly patients. We evaluated our outcomes of LRYGB in patients aged ≥ 55 years. METHODS: A total of 549 consecutive patients underwent LRYGB as primary operation and 132 were ≥ 55 years old. Patients were divided in two groups: group <55 years comprised 417 patients, with mean age (± SD) of 41.15 ± 8.47 years; group ≥ 55 years comprised 132 patients, with mean age of 59.43 ± 3.81 years. Mean preoperative body mass index was 47.01 ± 7.47 and 46.21 ± 7.47 respectively, whereas mean excess weight loss percent (EW%) was 88.06 ± 30.28 and 84.86 ± 29.87 %. Early morbidity (30 days) and outcomes at 6, 12, and 24 months follow-up were evaluated. RESULTS: Significant difference was found in operative time (84.19 ± 29.05 vs. 90.89 ± 30.95 min, p = 0.03). One conversion to open procedure occurred in group <55 years, whereas three occurred in group ≥ 55 years (p = 0.04). Intraoperative complications occurred in 22 patients (5.27 %) in group <55 years versus 19 in group ≥ 55 years (14.39 %), which was statistically significant (p = 0.001). One case of death occurred in the younger group. Overall postoperative morbidity rate was 18.7 % in group <55 years and 25.76 % in group ≥ 55 years, with no significant difference (p = 0.08). Mean EWL% at 12 months in group <55 years was 65.95.05 ± 26.96 versus 62.61 ± 41.78 in group ≥ 55 years, whereas at 24 months it was 65.08 ± 29.68 versus 64.48 ± 18.44 with no significant difference between the groups (p = 0.51; p = 0.92). CONCLUSIONS: LRYGB for patients ≥ 55 years achieves outcomes and complications rates comparable to the younger population. Patients should not be denied bariatric surgery for the age alone.

Desire for body contouring surgery after bariatric surgery: do body mass index and weight loss matter?

BACKGROUND: There is disparity between the number of postbariatric surgery subjects who desire body contouring and those who receive it due to lack of resources or insurance criteria. OBJECTIVES: The authors evaluate the desire for body contouring after bariatric surgery and its relationship with demographic patient characteristics. METHODS: Three hundred sixty patients who had undergone bariatric surgery procedures >1 year previously completed a questionnaire designed by the surgical team to analyze each patient's desire for body contouring by area (face, upper arm, upper back, chin/neck, chest/breast, waist/abdomen, lower back, rear/buttock), scored from 0 to 3 (do not want, want somewhat, want, want a great deal). Data were compared with patient characteristics, postoperative body mass index (BMI), amount of weight loss, and BMI difference (ΔBMI). RESULTS: Most patients desired body contouring surgery, with high or very high desire for waist/abdomen (62.2%), upper arm (37.6%), chest/breast (28.3%), and rear/buttock (35.6%) contouring. Many patients (36.4%) cited "very high" expectations for how body contouring might change their appearance. Patients >50 years old and >3 years postsurgery had a significantly lower desire. Patients with a ΔBMI >10 and with a weight loss >20 kg showed a significantly stronger overall desire for body contouring compared with other groups. CONCLUSIONS: Most patients desire body contouring surgery after bariatric surgery, and our multivariate analysis showed a significant positive association between female sex, younger age, amount of weight loss, and ΔBMI with desire for body contouring.

The Efficacy of Platelet-Rich Plasma Injection Therapy in Obese versus Non-Obese Patients with Knee Osteoarthritis: A Comparative Study.

Background/Objectives: Obesity is a common comorbidity in knee osteoarthritis (KOA) patients. Platelet-Rich Plasma (PRP) injection therapy may mitigate KOA. To further clarify potential patient selection for PRP injection therapy, we compared the outcomes in patients with different body mass index (BMI). Methods: A total of 91 patients with mild to moderate KOA were treated with three intra-articular PRP injections at 10 to 14-day intervals. Range of motion (ROM), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Visual Analogue Scale (VAS) were documented before and after the injections at 15 days, 6 months, 12 months, and at the last follow-up. Outcomes were compared between patients with a BMI over 30 kg/m2 (obese, n = 34) and under 30 kg/m2 (non-obese, n = 57). Results: Significant difference during the follow-up was detected in WOMAC score at the last follow-up favouring BMI under 30 group [17.8 ± 18.8 versus 10.5 ± 11.7, p = 0.023]. The odds ratio (OR) in BMI over 30 kg/m2 group for total knee arthroplasty was 3.5 (95% CI 0.3-40.1, p = 0.553), and OR for any arthroplasty was 7.5 (95% CI 0.8-69.8, p = 0.085) compared to non-obese patients. Conclusions: Obese patients benefitted from PRP injections in KOA but there is a minimal difference favouring non-obese patients in symptom alleviation in follow-up stages after 12 months. The risk of arthroplasty is higher for obese KOA patients.

Concomitant Panniculectomy in Abdominal Wall Reconstruction: A Narrative Review Focusing on Obese Patients.

The global prevalence of obesity continues to rise, contributing to an increased frequency of abdominal wall reconstruction procedures, particularly ventral hernia repairs, in individuals with elevated body mass indexes. Undertaking these operations in obese patients poses inherent challenges. This review focuses on the current literature in this area, with special attention to the impact of concomitant panniculectomy. Obese individuals undergoing abdominal wall reconstruction face elevated rates of wound healing complications and hernia recurrence. The inclusion of concurrent panniculectomy heightens the risk of surgical site occurrences but does not significantly influence hernia recurrence rates. While this combined approach can be executed in obese patients, caution is warranted, due to the higher risk of complications. Physicians should carefully balance and communicate the potential risks, especially regarding the increased likelihood of wound healing complications. Acknowledging these factors is crucial in shared decision making and ensuring optimal patient outcomes in the context of abdominal wall reconstruction and related procedures in the obese population.

Bempedoic acid: a new player for statin-intolerant patients and beyond.

PURPOSE OF REVIEW: Low-density lipoproteins (LDL) cause atherosclerotic cardiovascular disease, a condition associated with significant morbidity and mortality. Statins represent the cornerstone for preventing cardiovascular events in patients with elevated LDL-cholesterol (LDL-C) levels, however, they are associated with frequent musculoskeletal adverse effects, which lead to drug discontinuation or limit their use to low (and less effective) doses. Bempedoic acid (BA) is a newly approved, safe, cholesterol-lowering agent that inhibits ATP-citrate lyase, an enzyme upstream to 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase, the target of statins. Unlike statins, BA is not associated with musculoskeletal side effects, representing a promising drug for statin-intolerant patients. This review aims to summarize the current evidence on the efficacy, safety, and impact on clinical outcomes of BA, to review current indications for its use, and to highlight the ongoing clinical trials that will help deepen our knowledge of this promising compound. RECENT FINDINGS: BA improves clinical outcomes in statin-intolerant patients. Multiple ongoing studies are evaluating whether BA can be employed in other clinical settings. SUMMARY: BA safely and effectively reduces the levels of multiple atherogenic markers and can be employed to reach LDL-C targets independently from statin tolerance.

Component Separation Decreases Hernia Recurrence Rates in Abdominal Wall Reconstruction with Biologic Mesh.

BACKGROUND: It is not clear whether mesh-reinforced anterior component separation (CS) for abdominal wall reconstruction (AWR) results in better outcomes than mesh-reinforced primary fascial closure (PFC) without CS, particularly when acellular dermal matrix is used. The authors compared outcomes of CS versus PFC repair in AWR procedures aiming to determine whether CS results in better outcomes. METHODS: This retrospective study of prospectively collected data included 461 patients who underwent AWR with acellular dermal matrix during a 10-year period at an academic cancer center. The primary endpoint was hernia recurrence; the secondary outcome was surgical-site occurrence (SSO). RESULTS: A total of 322 patients (69.9%) who underwent mesh-reinforced AWR with CS (AWR-CS) and 139 (30.1%) who underwent AWR with PFC (AWR-PFC) without CS were compared. AWR-PFC repairs had a higher hernia recurrence rate than AWR-CS repairs (10.8% versus 5.3%; P = 0.002) but similar overall complication (28.8% versus 31.4%; P = 0.580) and SSO (18.7% versus 25.2%; P = 0.132) rates. CS repairs experienced significantly higher wound separation (17.7% versus 7.9%; P = 0.007), fat necrosis (8.7% versus 2.9%; P = 0.027), and seroma (5.6% versus 1.4%; P = 0.047) rates than PFC repairs. The best cutoff with respect to hernia recurrence was 7.1 cm of abdominal defect width. CONCLUSION: AWR-CS repair resulted in a lower hernia recurrence rate than AWR-PFC but, despite the additional surgery, had similar SSO rates on long-term follow-up. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Nuanced impacts of the invasive aquatic plant Crassula helmsii on Northwest European freshwater macroinvertebrate assemblages.

Invasive alien species are considered one of the greatest threats to global biodiversity, and are particularly problematic in aquatic systems. Given the foundational role of macrophytes in most freshwaters, alien aquatic plant invasions may drive strong bottom-up impacts on recipient biota. Crassula helmsii (New Zealand pygmyweed) is an Australasian macrophyte, now widespread in northwest Europe. Crassula helmsii rapidly invades small lentic waterbodies, where it is generally considered a serious threat to native biodiversity. The precise ecological impacts of this invasion remain poorly understood, however, particularly with respect to macroinvertebrates, which comprise the bulk of freshwater faunal biodiversity. We conducted a field study of ponds, ditches and small lakes across the core of C. helmsii's invasive range (United Kingdom, Belgium and the Netherlands), finding that invaded sites had higher macroinvertebrate taxon richness than uninvaded sites, and that many infrequent and rare macroinvertebrates co-occurred with C. helmsii. Alien macroinvertebrates were more abundant in C. helmsii sites, however, particularly the North American amphipod Crangonyx pseudogracilis. At the order level, water beetle (Coleoptera) richness and abundance were higher in C. helmsii sites, whereas true fly (Diptera) abundance was higher in uninvaded sites. Taxonomic and functional assemblage composition were both impacted by invasion, largely in relation to taxa and traits associated with detritivory, suggesting that the impacts of C. helmsii on macroinvertebrates are partly mediated by the availability and palatability of its detritus. The nuanced effects of C. helmsii on macroinvertebrates found here should encourage further quantitative research on the impacts of this invasive plant, and perhaps prompt a more balanced re-evaluation of its effects on native aquatic macrofauna.

Blockchain technology in Cardiovascular Medicine: a glance to the future? Results from a social media survey and future perspectives.

The leverage of digital facilities in medicine for disease diagnosis, monitoring, and medical history recording has become increasingly pivotal. However, the advancement of these technologies poses a significant challenge regarding data privacy, given the highly sensitive nature of medical information. In this context, the application of Blockchain technology, a digital system where information is stored in blocks and each block is linked to the one before, has the potential to enhance existing technologies through its exceptional security and transparency. This paradigm is of particular importance in cardiovascular medicine, where the prevalence of chronic conditions leads to the need for secure remote monitoring, secure data storage and secure medical history updating. Indeed, digital support for chronic cardiovascular pathologies is getting more and more crucial. This paper lays its rationale in three primary aims: 1) to scrutinize the existing literature for tangible applications of blockchain technology in the field of cardiology; 2) to report results from a survey aimed at gauging the reception of blockchain technology within the cardiovascular community, conducted on social media; 3) to conceptualize a web application tailored specifically to cardiovascular care based on blockchain technology. We believe that Blockchain technology may contribute to a breakthrough in healthcare digitalization, especially in the field of cardiology; in this context, we hope that the present work may be inspiring for physicians and healthcare stakeholders.

A 25-year-long journey into interventional cardiology: looking back, and rushing forward.

Cardiovascular disease remains decade after decade a leading cause of mortality, morbidity and resource use globally as well as locally. We have had the opportunity of being involved in several iterative breakthroughs in invasive cardiovascular procedures, ranging from the advent of coronary stents to transcatheter mitral valve repair. Building up such extensive clinical and research experience, we hereby present 25 years of cardiovascular interventions at Pineta Grande Hospital and Casa di Salute S. Lucia, respectively in Castel Volturno, and S. Giuseppe Vesuviano, both in the Italian Campania region, where the same team of interventional cardiologists has managed to adopt and master several cardiovascular innovations for the benefit of thousands of patients. Our experience showcases the evolution of invasive cardiology, especially in diagnostic and therapeutic practices. Key highlights include advancements in coronary procedures, with the introduction of bare-metal stents, drug-eluting stents and drug-coated balloons, despite the setback of bioresorbable vascular scaffolds, as well as transcatheter aortic valve implantation and innovative approaches to mitral regurgitation. Furthermore, this overview scrutinizes procedural challenges, patient outcomes, and quality of life improvements, providing a rich tapestry of clinical experiences and research insights. It serves as a testament to the dynamic nature of interventional cardiology, offering a forward-looking perspective on future trends and technologies. We hope that this overview will prove an informative and insightful read for those seeking to understand the intricate journey of invasive cardiovascular care over the past decades and its trajectory into the future.

Features and outcomes of bailout repeat transcatheter aortic valve implantation (TAVI): the Bailout Acute TAVI-in-TAVI to Lessen Events (BATTLE) international registry.

AIM: Transcatheter aortic valve implantation (TAVI) is a mainstay in the management of severe aortic stenosis in patients with intermediate to prohibitive surgical risk. When a single TAVI device fails and cannot be retrieved, TAVI-in-TAVI must be performed acutely, but outcomes of bailout TAVI-in-TAVI have been incompletely appraised. We aimed at analyzing patient, procedural and outcome features of patients undergoing bailout TAVI-in-TAVI in a multicenter registry. METHODS: Details of patients undergoing bailout TAVI-in-TAVI, performed acutely or within 24 h of index TAVI, in 6 international high-volume institutions, were collected. For every case provided, 2 same-week consecutive controls (prior TAVI, and subsequent TAVI) were provided. Outcomes of interest were procedural and long-term events, including death, myocardial infarction, stroke, access site complication, major bleeding, and reintervention, and their composite (i.e. major adverse events [MAE]). RESULTS: A total of 106 patients undergoing bailout TAVI-in-TAVI were included, as well as 212 controls, for a total of 318 individuals. Bailout TAVI-in-TAVI was less common in younger patients, those with higher body mass index, or treated with Portico/Navitor or Sapien devices (all p < 0.05). Bailout TAVI-in-TAVI was associated with higher in-hospital rates of death, emergency surgery, MAE, and permanent pacemaker implantation (all p < 0.05). Long-term follow-up showed that bailout TAVI-in-TAVI was associated with higher rates of death and MAE (both < 0.05). Similar findings were obtained at adjusted analyses (all p < 0.05). However, censoring early events, outlook was not significantly different when comparing the two groups (p = 0.897 for death, and p = 0.645 for MAE). CONCLUSIONS: Bail-out TAVI-in-TAVI is associated with significant early and long-term mortality and morbidity. Thus, meticulous preprocedural planning and sophisticated intraprocedural techniques are of paramount importance to avoid these emergency procedures.

Long-term outcomes following transcatheter aortic valve implantation with the Portico self-expanding valve.

AIM: Transcatheter aortic valve implantation (TAVI) is a mainstay in the management of severe aortic valve stenosis in elderly patients, but there is uncertainty on their long-term effectiveness. We aimed to assess the long-term outcome of patients undergoing TAVI with the Portico valve. METHODS: We retrospectively collected the data on patients in whom TAVI with Portico was attempted from 7 high-volume centres. Only patients theoretically eligible for 3 or more years of follow-up were included. Clinical outcomes, including death, stroke, myocardial infarction, reintervention for valve degeneration and hemodynamic valve performance were systematically assessed. RESULTS: A total of 803 patients were included, with 504 (62.8%) women, mean age of 82 years, median EuroSCORE II of 3.1%, and 386 (48.1%) subjects at low/moderate risk. The median follow-up was 3.0 years (3.0; 4.0). The composite of death, stroke, myocardial infarction, and reintervention for valve degeneration occurred in 37.5% (95% confidence interval: 34.1-40.9%), with all-cause death in 35.1% (31.8-38.4%), stroke in 3.4% (1.3-3.4%), myocardial infarction in 1.0% (0.3-1.5%), and reintervention for valve degeneration in 1.1% (0.6-2.1%). The mean aortic valve gradient at follow-up was 8.1 ± 4.6 mmHg, and at least moderate aortic regurgitation was present in 9.1% (6.7-12.3%). Independent predictors of major adverse events or death were: peripheral artery disease, chronic obstructive pulmonary disease, estimated glomerular filtration rate, atrial fibrillation, prior pacemaker implantation, EuroSCORE II, and reduced left ventricular ejection fraction (all p < 0.05). CONCLUSIONS: Portico use is associated with favorable long-term clinical outcomes. Clinical outcomes were largely impacted by baseline risk factors and surgical risk.

P2Y12 Inhibition in Patients Requiring Oral Anticoagulation After Percutaneous Coronary Intervention: The SWAP-AC-2 Study.

BACKGROUND: Among patients treated with a novel oral anticoagulant (NOAC) undergoing percutaneous coronary intervention (PCI), combination therapy with clopidogrel (ie, known as dual antithrombotic therapy [DAT]) is the treatment of choice. However, there are concerns for individuals with impaired response to clopidogrel. OBJECTIVES: The authors sought to assess the pharmacodynamic (PD) effects of clopidogrel vs low-dose ticagrelor in patients with impaired clopidogrel response assessed by the ABCD-GENE score. METHODS: This was a prospective, randomized PD study of NOAC-treated patients undergoing PCI. Patients with an ABCD-GENE score ≥10 (n = 39), defined as having impaired clopidogrel response, were randomized to low-dose ticagrelor (n = 20; 60 mg twice a day) or clopidogrel (n = 19; 75 mg once a day). Patients with an ABCD-GENE score <10 (n = 42) were treated with clopidogrel (75 mg once a day; control cohort). PD assessments at baseline and 30 days post-randomization (trough and peak) were performed to assess P2Y12 signaling (VerifyNow P2Y12 reaction units [PRU], light transmittance aggregometry, and vasodilator-stimulated phosphoprotein); makers of thrombosis not specific to P2Y12 signaling were also assessed. The primary endpoint was PRU (trough levels) at 30 days. RESULTS: At 30 days, PRU levels were reduced with ticagrelor-based DAT compared with clopidogrel-based DAT at trough (23.0 [Q1-Q3: 3.0-46.0] vs 154.5 [Q1-Q3: 77.5-183.0]; P < 0.001) and peak (6.0 [Q1-Q3: 4.0-14.0] vs 129.0 [Q1-Q3: 66.0-171.0]; P < 0.001). Trough PRU levels in the control arm (104.0 [Q1-Q3: 35.0-167.0]) were higher than ticagrelor-based DAT (P = 0.005) and numerically lower than clopidogrel-based DAT (P = 0.234). Results were consistent by light transmittance aggregometry and vasodilator-stimulated phosphoprotein. Markers measuring other pathways leading to thrombus formation were largely unaffected. CONCLUSIONS: In NOAC-treated patients undergoing PCI with an ABCD-GENE score ≥10, ticagrelor-based DAT using a 60-mg, twice-a-day regimen reduced platelet P2Y12 reactivity compared with clopidogrel-based DAT. (Tailoring P2Y12 Inhibiting Therapy in Patients Requiring Oral Anticoagulation After PCI [SWAP-AC-2]; NCT04483583).