Immediate versus staged complete revascularisation in patients presenting with acute coronary syndrome and multivessel coronary disease (BIOVASC): a prospective, open-label, non-inferiority, randomised trial.

BACKGROUND: In patients with acute coronary syndrome and multivessel coronary disease, complete revascularisation by percutaneous coronary intervention (PCI) is associated with improved clinical outcomes. We aimed to investigate whether PCI for non-culprit lesions should be attempted during the index procedure or staged. METHODS: This prospective, open-label, non-inferiority, randomised trial was done at 29 hospitals across Belgium, Italy, the Netherlands, and Spain. We included patients aged 18-85 years presenting with ST-segment elevation myocardial infarction or non-ST-segment elevation acute coronary syndrome and multivessel (ie, two or more coronary arteries with a diameter of 2·5 mm or more and ≥70% stenosis based on visual estimation or positive coronary physiology testing) coronary artery disease with a clearly identifiable culprit lesion. A web-based randomisation module was used to randomly assign patients (1:1), with a random block size of four to eight, stratified by study centre, to undergo immediate complete revascularisation (PCI of the culprit lesion first, followed by other non-culprit lesions deemed to be clinically significant by the operator during the index procedure) or staged complete revascularisation (PCI of only the culprit lesion during the index procedure and PCI of all non-culprit lesions deemed to be clinically significant by the operator within 6 weeks after the index procedure). The primary outcome was the composite of all-cause mortality, myocardial infarction, any unplanned ischaemia-driven revascularisation, or cerebrovascular events at 1 year after the index procedure. Secondary outcomes included all-cause mortality, myocardial infarction, and unplanned ischaemia-driven revascularisation at 1 year after the index procedure. Primary and secondary outcomes were assessed in all randomly assigned patients by intention to treat. Non-inferiority of immediate to staged complete revascularisation was considered to be met if the upper boundary of the 95% CI of the hazard ratio (HR) for the primary outcome did not exceed 1·39. This trial is registered with ClinicalTrials.gov, NCT03621501. FINDINGS: Between June 26, 2018, and Oct 21, 2021, 764 patients (median age 65·7 years [IQR 57·2-72·9] and 598 [78·3%] males) were randomly assigned to the immediate complete revascularisation group and 761 patients (median age 65·3 years [58·6-72·9] and 589 [77·4%] males) were randomly assigned to the staged complete revascularisation group, and were included in the intention-to-treat population. The primary outcome at 1 year occurred in 57 (7·6%) of 764 patients in the immediate complete revascularisation group and in 71 (9·4%) of 761 patients in the staged complete revascularisation group (HR 0·78, 95% CI 0·55-1·11, pnon-inferiority=0·0011). There was no difference in all-cause death between the immediate and staged complete revascularisation groups (14 [1·9%] vs nine [1·2%]; HR 1·56, 95% CI 0·68-3·61, p=0·30). Myocardial infarction occurred in 14 (1·9%) patients in the immediate complete revascularisation group and in 34 (4·5%) patients in the staged complete revascularisation group (HR 0·41, 95% CI 0·22-0·76, p=0·0045). More unplanned ischaemia-driven revascularisations were performed in the staged complete revascularisation group than in the immediate complete revascularisation group (50 [6·7%] patients vs 31 [4·2%] patients; HR 0·61, 95% CI 0·39-0·95, p=0·030). INTERPRETATION: In patients presenting with acute coronary syndrome and multivessel disease, immediate complete revascularisation was non-inferior to staged complete revascularisation for the primary composite outcome and was associated with a reduction in myocardial infarction and unplanned ischaemia-driven revascularisation. FUNDING: Erasmus University Medical Center and Biotronik.

Incidence of new-onset hypertension before, during, and after the COVID-19 pandemic: a 7-year longitudinal cohort study in a large population.

BACKGROUND: While the augmented incidence of diabetes after COVID-19 has been widely confirmed, controversial results are available on the risk of developing hypertension during the COVID-19 pandemic. METHODS: We designed a longitudinal cohort study to analyze a closed cohort followed up over a 7-year period, i.e., 3 years before and 3 years during the COVID-19 pandemic, and during 2023, when the pandemic was declared to be over. We analyzed medical records of more than 200,000 adults obtained from a cooperative of primary physicians from January 1, 2017, to December 31, 2023. The main outcome was the new diagnosis of hypertension. RESULTS: We evaluated 202,163 individuals in the pre-pandemic years and 190,743 in the pandemic years, totaling 206,857 when including 2023 data. The incidence rate of new hypertension was 2.11 (95% C.I. 2.08-2.15) per 100 person-years in the years 2017-2019, increasing to 5.20 (95% C.I. 5.14-5.26) in the period 2020-2022 (RR = 2.46), and to 6.76 (95% C.I. 6.64-6.88) in 2023. The marked difference in trends between the first and the two successive observation periods was substantiated by the fitted regression lines of two Poisson models conducted on the monthly log-incidence of hypertension. CONCLUSIONS: We detected a significant increase in new-onset hypertension during the COVID-19 pandemic, which at the end of the observation period affected ~ 20% of the studied cohort, a percentage higher than the diagnosis of COVID-19 infection within the same time frame. This observation suggests that increased attention to hypertension screening should not be limited to individuals who are aware of having contracted the infection but should be extended to the entire population.

Achieving a Systolic Blood Pressure Below 130 mmHg Reduces the Incidence of Cardiovascular Events in Hypertensive Patients with Echocardiographic Left Ventricular Hypertrophy.

Background: Recent reports have evidenced an increased mortality rate in hypertensive patients with electrocardiographic left ventricular hypertrophy (ECG-LVH) achieving systolic blood pressure (SBP) <130 mmHg. However, to the best of our knowledge, the actual effects of blood pressure reduction to the ≤130/80 mmHg target on the incidence of cardiovascular (CV) events have never been determined in hypertensive patients with a diagnosis of left ventricular hypertrophy based on echocardiographic criteria (Echo-LVH). Methods: To fill this long-standing knowledge gap, we harnessed a population of 9511 hypertensive patients, followed-up for 33.6 [interquartile range 7.9-72.7] months. The population was divided into six groups according to the average SBP achieved during the follow-up (≤130, 130-139, and ≥140 mmHg) and absence/presence of Echo-LVH. The primary endpoint was a composite of fatal or nonfatal myocardial infarction and stroke, sudden cardiac death, heart failure requiring hospitalization, revascularization, and carotid stenting. Secondary endpoints included atrial fibrillation and transient ischemic attack. Results: During the follow-up, achieved SBP and diastolic blood pressure (DBP) were comparable between patients with and without Echo-LVH. Strikingly, the rates of primary and secondary endpoints were significantly higher in patients with Echo-LVH and SBP >130 mmHg, reaching the highest values in the Echo-LVH group with SBP ≥140 mmHg. By separate Cox multivariable regressions, after adjusting for potential confounders, both primary and secondary endpoints were significantly associated with SBP ≥140 mmHg and Echo-LVH. Instead, DBP reduction ≤80 mmHg was associated with a significant increased rate of secondary events. Conclusions: In hypertensive patients with Echo-LVH, achieving an average in-treatment SBP target ≤130 mmHg has a beneficial prognostic impact on incidence of CV events. SIGNIFICANCE STATEMENT: Contrary to recent findings, achieving in-treatment SBP ≤130 mmHg lowers the incidence of CV events in hypertensive patients with Echo-LVH. However, reducing DBP ≤80 mmHg is linked to increased CV complications. Cox multivariable regression models, considering potential confounders, reveal that the rate of hard and soft CV events is significantly associated with Echo-LVH and SBP ≥140 mmHg. Our data indicate that therapeutic strategies for Echo-LVH patients should target SBP ≤130 mmHg while avoiding lowering DBP ≤80 mmHg.

Annual Research Review: 'There, the dance is - at the still point of the turning world' - dynamic systems perspectives on coregulation and dysregulation during early development.

During development we transition from coregulation (where regulatory processes are shared between child and caregiver) to self-regulation. Most early coregulatory interactions aim to manage fluctuations in the infant's arousal and alertness; but over time, coregulatory processes become progressively elaborated to encompass other functions such as sociocommunicative development, attention and executive control. The fundamental aim of coregulation is to help maintain an optimal 'critical state' between hypo- and hyperactivity. Here, we present a dynamic framework for understanding child-caregiver coregulatory interactions in the context of psychopathology. Early coregulatory processes involve both passive entrainment, through which a child's state entrains to the caregiver's, and active contingent responsiveness, through which the caregiver changes their behaviour in response to behaviours from the child. Similar principles, of interactive but asymmetric contingency, drive joint attention and the maintenance of epistemic states as well as arousal/alertness, emotion regulation and sociocommunicative development. We describe three ways in which active child-caregiver regulation can develop atypically, in conditions such as Autism, ADHD, anxiety and depression. The most well-known of these is insufficient contingent responsiveness, leading to reduced synchrony, which has been shown across a range of modalities in different disorders, and which is the target of most current interventions. We also present evidence that excessive contingent responsiveness and excessive synchrony can develop in some circumstances. And we show that positive feedback interactions can develop, which are contingent but mutually amplificatory child-caregiver interactions that drive the child further from their critical state. We discuss implications of these findings for future intervention research, and directions for future work.

Robotic-assisted versus conventional laparoscopic ICG-fluorescence lymphatic-sparing palomo varicocelectomy: a comparative retrospective study of techniques and outcomes.

PURPOSE: This study aimed to compare techniques and outcomes of robotic-assisted varicocelectomy (RAV) and laparoscopic varicocelectomy (LV). METHODS: The medical records of 40 patients, who received RAV and LV over a 2-year period, were retrospectively analyzed. Palomo lymphatic-sparing varicocelectomy using ICG fluorescence was adopted in all cases. Three 5-mm trocars were placed in LV, whereas four ports, three 8-mm and one 5-mm, were placed in RAV. The spermatic vessels were ligated using clips in LV and ligatures in RAV. The two groups were compared regarding patient baseline and operative outcomes. RESULTS: All patients, with median age of 14 years (range 11-17), had left grade 3 varicocele according to Dubin-Amelar. All were symptomatic and 33/40 (82.5%) presented left testicular hypotrophy. All procedures were completed without conversion. The average operative time was significantly shorter in LV [20 min (range 11-30)] than in RAV [34.5 min (range 30-46)] (p = 0.001). No significant differences regarding analgesic requirement and hospitalization were observed (p = 0.55). At long-term follow-up (30 months), no complications occurred in both groups. The cosmetic outcome was significantly better in LV than RAV at 6-month and 12-month evaluations (p = 0.001). The total cost was significantly lower in LV (1.587,07 €) compared to RAV (5.650,31 €) (p = 0.001). CONCLUSION: RAV can be safely and effectively performed in pediatric patients, with the same excellent outcomes as conventional laparoscopic procedure. Laparoscopy has the advantages of faster surgery, smaller instruments, better cosmesis and lower cost than robotics. To date, laparoscopy remains preferable to robotics to treat pediatric varicocele.

Video-assisted anal fistula treatment (VAAFT) combined with ozonide oil dressing: standardization of technique in pediatric patients.

BACKGROUND: Anal fistula and perianal abscess are commonly acquired anorectal pathologies in children. Surgical treatment options commonly adopted are fistulotomy, fistulectomy, cutting seton placement, and more recently video-assisted anal fistula treatment (VAAFT). Optimal postoperative wound dressing remains debated. This study aimed to report our series of pediatric patients, who received VAAFT and postoperative wound dressing using ozonide oil. METHODS: All patients who underwent VAAFT between August 2018 and May 2023 were included in the study. Demographics, clinical features, pre-operative imaging, surgical details, outcome, and mid-term outcome data were retrospectively reviewed for each patient. All VAAFT procedures were performed under general anesthesia and using a 10-Ch fistuloscope. RESULTS: Thirty-three VAAFT procedures were performed in 30 patients over the study period. The median patient age was 5.7 years (range 1.75-14). Anal fistula was idiopathic in 26/30 (86.6%), iatrogenic in 2/30 (6.7%), and secondary to Crohn's disease in 2/30 (6.7%). The median duration of surgery was 23 min (range 18-40). All patients received ozonide oil dressing twice a day for 5 weeks postoperatively. The median hospital stay was 24 h (range 9-36). The median healing time was 28 days (range 17-39). With a median follow-up of 2 years (range 0.5-5), disease recurrence occurred in 3/30 (10%) patients with idiopathic fistula, who were re-operated using the same technique, with no further recurrence. No fecal incontinence or soiling was observed. CONCLUSION: Our series confirmed that VAAFT is a safe and effective technique to treat children with perianal fistula. The technique is versatile, allowing to treat fistulae of different etiologies. Postoperative course was painless and fast. Future comparative prospective studies are needed to better establish these conclusions.

Reuse of polymeric waste for the treatment of marine water polluted by diesel.

Accidental diesel spills can occur in marine environments such as harbors, leading to adverse effects on the environmental compartment and humans. This study proposes the surgical mask as an affordable and sustainable adsorbent for the remediation of diesel-contaminated seawater to cope with the polymeric waste generated monthly in hospital facilities. This approach can also be helpful considering a possible future pandemic, alleviating the pressure on the waste management system by avoiding improper mask incineration and landfilling, as instead occurred during the previous COVID-19. Batch adsorption-desorption experiments revealed a complete diesel removal from seawater after 120 min with the intact laceless mask, which showed an adsorption capacity of up to 3.43 g/g. The adsorption curve was better predicted via Weber and Morris's kinetic (R2 = 0.876) and, in general, with Temkin isotherm (R2 = 0.965-0.996) probably due to the occurrence of chemisorption with intraparticle diffusion as one of the rates-determining steps. A hysteresis index of 0.23-0.36 was obtained from the desorption isotherms, suggesting that diesel adsorption onto surgical masks was faster than the desorption mechanism. Also, the effect of pH, ionic strength and temperature on diesel adsorption was examined. The results from the reusability tests indicated that the surgical mask can be regenerated for 5 consecutive cycles while decreasing the adsorption capacity by only approximately 11%.

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.

Efficacy of a Drug-Eluting Stent Versus Bare Metal Stents for Symptomatic Femoropopliteal Peripheral Artery Disease: Primary Results of the EMINENT Randomized Trial.

BACKGROUND: A clear patency benefit of a drug-eluting stent (DES) over bare metal stents (BMSs) for treating peripheral artery disease of the femoropopliteal segment has not been definitively demonstrated. The EMINENT study (Trial Comparing Eluvia Versus Bare Metal Stent in Treatment of Superficial Femoral and/or Proximal Popliteal Artery) was designed to evaluate the patency of the Eluvia DES (Boston Scientific, Marlborough, MA), a polymer-coated paclitaxel-eluting stent, compared with BMSs for the treatment of femoropopliteal artery lesions. METHODS: EMINENT is a prospective, randomized, controlled, multicenter European study with blinded participants and outcome assessment. Patients with symptomatic peripheral artery disease (Rutherford category 2, 3, or 4) of the native superficial femoral artery or proximal popliteal artery with stenosis ≥70%, vessel diameter of 4 to 6 mm, and total lesion length of 30 to 210 mm were randomly assigned 2:1 to treatment with DES or BMS. The primary effectiveness outcome was primary patency at 12 months, defined as independent core laboratory-assessed duplex ultrasound peak systolic velocity ratio ≤2.4 in the absence of clinically driven target lesion revascularization or surgical bypass of the target lesion. Primary sustained clinical improvement was a secondary outcome defined as a decrease in Rutherford classification of ≥1 categories compared with baseline without a repeat target lesion revascularization. Health-related quality of life and walking function were assessed. RESULTS: A total of 775 patients were randomly assigned to treatment with DES (n=508) or commercially available BMSs (n=267). Baseline clinical, demographic, and lesion characteristics were similar between the study groups. Mean lesion length was 75.6±50.3 and 72.2±47.0 mm in the DES and BMS groups, respectively. The 12-month incidence of primary patency for DES treatment (83.2% [337 of 405]) was significantly greater than for BMS (74.3% [165 of 222]; P<0.01). Incidence of primary sustained clinical improvement was greater among patients treated with the DES than among those who received a BMS (83.0% versus 76.6%; P=0.045). The health-related quality of life dimensions of mobility and pain/discomfort improved for the majority of patients in both groups (for 66.4% and 53.6% of DES-treated and for 64.2% and 58.1% of BMS-treated patients, respectively) but did not differ significantly. At 12 months, no statistical difference was observed in all-cause mortality between patients treated with the DES or BMS (2.7% [13 of 474] versus 1.1% [3 of 263]; relative risk, 2.4 [95% CI, 0.69-8.36]; P=0.15). CONCLUSIONS: By demonstrating superior 1-year primary patency, the results of the EMINENT randomized study support the benefit of using a polymer-based paclitaxel-eluting stent as a first-line stent-based intervention for patients with symptomatic peripheral artery disease attributable to femoropopliteal lesions. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02921230.

Effects on Mortality and Major Bleeding of Radial Versus Femoral Artery Access for Coronary Angiography or Percutaneous Coronary Intervention: Meta-Analysis of Individual Patient Data From 7 Multicenter Randomized Clinical Trials.

BACKGROUND: In some randomized clinical trials, transradial access (TRA) compared with transfemoral access (TFA) was associated with lower mortality in patients with coronary artery disease undergoing invasive management. We analyzed the effects of TRA versus TFA across multicenter randomized clinical trials and whether these associations are modified by patient or procedural characteristics. METHODS: We performed an individual patient data meta-analysis of multicenter randomized clinical trials comparing TRA with TFA among patients undergoing coronary angiography with or without percutaneous coronary intervention. The primary outcome was all-cause mortality and the co-primary outcome was major bleeding at 30 days. The primary analysis was conducted by 1-stage mixed-effects models on the basis of the intention-to-treat cohort. The effect of access site on mortality and major bleeding was assessed further by multivariable analysis. The relationship among access site, bleeding, and mortality was investigated by natural effect model mediation analysis with multivariable adjustment. RESULTS: A total of 21 600 patients (10 775 TRA, 10 825 TFA) from 7 randomized clinical trials were included. The median age was 63.9 years, 31.9% were women, 95% presented with acute coronary syndrome, and 75.2% underwent percutaneous coronary intervention. All-cause mortality (1.6% versus 2.1%; hazard ratio, 0.77 [95% CI, 0.63-0.95]; P=0.012) and major bleeding (1.5% versus 2.7%; odds ratio, 0.55 [95% CI, 0.45-0.67]; P<0.001) were lower with TRA. Subgroup analyses for mortality showed consistent results, except for baseline hemoglobin level (Pinteraction=0.003), indicating that the benefit of TRA was substantial in patients with moderate or severe anemia, whereas it was not significant in patients with milder or no baseline anemia. After adjustment, TRA remained associated with 24% and 51% relative risk reduction of all-cause mortality and major bleeding, respectively. A mediation analysis showed that the benefit of TRA on mortality was only partially driven by major bleeding prevention and ancillary mechanisms are required to fully explain the causal association. CONCLUSIONS: TRA is associated with lower all-cause mortality and major bleeding at 30 days compared with TFA. The effect on mortality was driven by patients with anemia. The reduction in major bleeding only partially explains the mortality benefit. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42018109664.

P2Y12 Inhibitors Monotherapy in Patients Undergoing Complex vs Non-Complex Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Trials.

BACKGROUND: Monotherapy with P2Y12 inhibitors (P2Y12i) is emerging as alternative strategy to dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). However, early withdrawal of aspirin as part of P2Y12i monotherapy regimens may pose concerns in high-risk patients, such as those undergoing complex PCI. Our aim was to evaluate the efficacy and safety of P2Y12i monotherapy after a short course of DAPT (1-3-month) compared with standard DAPT (≥12-month) according to PCI complexity. METHODS: We performed a meta-analysis of randomized trials using random effects models to combine hazard ratios (HRs) with 95% confidence intervals (CIs). Within-trial interactions were pooled to estimate heterogeneity between complex and noncomplex PCI strata. The study protocol was registered in the PROSPERO (CRD42021291027). RESULTS: We identified 5 trials including 31,627 patients, of whom 8,328 (26.3%) underwent complex PCI. P2Y12i monotherapy compared with standard DAPT was associated with a similar risk of all-cause death, stent thrombosis, and stroke, with no evidence for interaction between complex and noncomplex PCI. We found heterogeneity in the treatment effect of P2Y12i monotherapy vs standard DAPT with respect to myocardial infarction (P-interaction = 0.027). Compared with standard DAPT, P2Y12i monotherapy decreased the risk of myocardial infarction in complex PCI (HR 0.77, 95%CI 0.60-0.99, P = .042), but not in noncomplex PCI patients (HR 1.09, 95%CI 0.90-1.30, P = .382). The risk of major bleeding was significantly reduced by P2Y12i monotherapy with a consistent treatment effect (P-interaction = 0.699) in both complex and noncomplex PCI strata. CONCLUSIONS: Patients undergoing complex PCI may derive more benefit and less harm from P2Y12i monotherapy after early aspirin withdrawal compared with standard DAPT.

Rationale and design of the PARTHENOPE trial: A two-by-two factorial comparison of polymer-free vs biodegradable-polymer drug-eluting stents and personalized vs standard duration of dual antiplatelet therapy in all-comers undergoing PCI.

BACKGROUND: Over the past few decades, percutaneous coronary intervention (PCI) has undergone significant advancements as a result of the combination of device-based and drug-based therapies. These iterations have led to the development of polymer-free drug-eluting stents. However, there is a scarcity of data regarding their clinical performance. Furthermore, while various risk scores have been proposed to determine the optimal duration of dual antiplatelet therapy (DAPT), none of them have undergone prospective validation within the context of randomized trials. DESIGN: The PARTHENOPE trial is a phase IV, prospective, randomized, multicenter, investigator-initiated, assessor-blind study being conducted at 14 centers in Italy (NCT04135989). It includes 2,107 all-comers patients with minimal exclusion criteria, randomly assigned in a 2-by-2 design to receive either the Cre8 amphilimus-eluting stent or the SYNERGY everolimus-eluting stent, along with either a personalized or standard duration of DAPT. Personalized DAPT duration is determined by the DAPT score, which accounts for both bleeding and ischemic risks. Patients with a DAPT score <2 (indicating higher bleeding than ischemic risk) receive DAPT for 3 or 6 months for chronic or acute coronary syndrome, respectively, while patients with a DAPT score ≥2 (indicating higher ischemic than bleeding risk) receive DAPT for 24 months. Patients in the standard DAPT group receive DAPT for 12 months. The trial aims to establish the noninferiority between stents with respect to a device-oriented composite end point of cardiovascular death, target-vessel myocardial infarction, or clinically-driven target-lesion revascularization at 12 months after PCI. Additionally, the trial aims to demonstrate the superiority of personalized DAPT compared to a standard approach with respect to a net clinical composite of all-cause death, any myocardial infarction, stroke, urgent target-vessel revascularization, or type 2 to 5 bleeding according to the Bleeding Academic Research Consortium criteria at 24-months after PCI. SUMMARY: The PARTHENOPE trial is the largest randomized trial investigating the efficacy and safety of a polymer-free DES with a reservoir technology for drug-release and the first trial evaluating a personalized duration of DAPT based on the DAPT score. The study results will provide novel insights into the optimizing the use of drug-eluting stents and DAPT in patients undergoing PCI.

Acute advanced aortic stenosis.

Acute decompensation often represents the onset of symptoms associated with severe degenerative aortic stenosis (AS) and usually complicates the clinical course of the disease with a dismal impact on survival and quality of life. Several factors may derange the faint balance between left ventricular preload and afterload and precipitate the occurrence of symptoms and signs of acute heart failure (HF). A standardized approach for the management of this condition is currently lacking. Medical therapy finds very limited application in this setting, as drugs usually indicated for the control of acute HF might worsen hemodynamics in the presence of AS. Urgent aortic valve replacement is usually performed by transcatheter than surgical approach whereas, over the last decades, percutaneous balloon valvuloplasty gained renewed space as bridge to definitive therapy. This review focuses on the pathophysiological aspects of acute advanced AS and summarizes current evidence on its management.

Contrast media volume reduction with the DyeVertTM system to prevent acute kidney injury in stable patients undergoing coronary procedures.

BACKGROUND: Contrast associated acute kidney injury (CA-AKI) can lead to an increased risk of adverse events. Contrast media (CM) volume reduction has been advocated as a pivotal strategy to prevent CA-AKI in stable patients undergoing percutaneous coronary procedures. AIMS: To compare the effectiveness of CM volume reduction with the DyeVertTM system versus conventional strategy in reducing the risk of CA-AKI. METHODS: We prospectively collected data from 136 patients with stable coronary artery disease at high risk of CA-AKI treated with left ventricular end diastolic pressure (LVEDP)- guided hydration and undergoing interventions with the use of the DyeVertTM (Osprey Medical Inc.) system. Patients previously enrolled in the LVEDP-guided hydration arm of the "Renal Insufficiency Following Contrast MEDIA Administration triaL III" (REMEDIAL III) were considered as controls. Propensity score was used to perform 1:1 matching to adjust for major confounders. The primary outcome was the occurrence of CA-AKI, as defined by an absolute increase of creatinine values ≥0.3 mg/dL at 48 h. RESULTS: Patients in the DyeVert group were treated with a significant lower CM volume (median: 47.5 vs. 84.0 mL, p < 0.001). The trend in creatinine increase was lower (p = 0.004) and the Δ of creatinine (0-48 h) showed a higher drop (-0.18 vs. -0.10 mg/dL, p = 0.036) in the DyeVert group. The risk of CA-AKI was significantly lower in DyeVert group compared to control group (5.1% vs. 16.8%; odds ratio 0.27, 95% confidence interval [0.12-0.61]). CONCLUSIONS: CM volume reduction with the DyeVertTM system seems to be superior to conventional strategies in reducing the occurrence of CA-AKI.

Randomized clinical trial of abluminus DES+ sirolimus-eluting stent versus everolimus-eluting DES for percutaneous coronary intervention in patients with diabetes mellitus: An optical coherence tomography study.

BACKGROUND: Diabetic patients are at higher risk of recurrent adverse events following percutaneous coronary intervention (PCI) than the nondiabetics. Despite the introduction of new generation drug-eluting stents, their efficacy in the diabetics is still limited. AIMS: To evaluate the efficacy of the Abluminus DES+ biodegradable polymer sirolimus-eluting stent in reducing neointimal hyperplasia in diabetic patients, compared to a durable polymer everolimus-eluting stent (DP-EES). METHODS: A total of 131 patients with diabetes and coronary artery disease were enrolled in six Italian centers and randomized in a 2:1 fashion to PCI with Abluminus DES+ or DP-EES: 85 were assigned to Abluminus DES+ and 46 to DP-EES. The primary endpoint was optimal coherence tomography (OCT)-derived neointimal volume at 9-12 months. Secondary endpoints included OCT-derived neointimal area, neointimal volume obstruction and adverse clinical events. RESULTS: The primary endpoint, neointimal volume, did not differ between Abluminus DES+ and DP-EES (29.11 ± 18.90 mm3 vs. 25.48 ± 17.04 mm3 , p = 0.40) at 9-12-month follow-up. This finding remained consistent after weighing for the sum of stents lengths (1.14 ± 0.68 mm3 vs. 0.99 ± 0.74 mm3 for Abluminus DES+ and DP-EES, respectively, p = 0.38). Similarly, other OCT-derived and clinical secondary endpoints did not significantly differ between the two groups. Rate of target lesion failure was high in both groups (21.2% for Abluminus DES+ and 19.6% for DP-EES). CONCLUSIONS: This preliminary study failed to demonstrate the superiority of the Abluminus DES+ over the DP-EES in diabetic patients in terms of neointimal proliferation.

Periprocedural myocardial infarction in patients undergoing complex versus noncomplex percutaneous coronary intervention.

BACKGROUND: Limited data are available on the risk of periprocedural myocardial infarction (MI) in patients undergoing complex versus noncomplex percutaneous coronary intervention (PCI). METHODS: We assessed the risk of periprocedural MI according to the fourth Universal definition of myocardial infarction (UDMI) and several other criteria among patients undergoing elective PCI in a prospective, single-center registry. Complex PCI included at least one of the following: 3 coronary vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, treatment of chronic total occlusion, and use of rotational atherectomy. RESULTS: Between 2017 and 2021, we included 1010 patients with chronic coronary syndrome, of whom 226 underwent complex PCI (22.4%). The rate of periprocedural MI according to the fourth UDMI was significantly higher in complex compared to noncomplex PCI patients (26.5% vs. 14.5%, p < 0.001). Additionally, periprocedural MI was higher in the complex PCI group using SCAI (4% vs. 1.1%, p = 0.009), ARC-2 (13.7% vs. 8.0%, p = 0.013), ISCHEMIA (5.8% vs. 1.7%, p = 0.002), and EXCEL criteria (4.9% vs. 2.0%, p = 0.032). SYNTAX periprocedural MI occurred at low rates in both groups (0.9% vs. 0.6%, p = 0.657). Complex PCI was an independent predictor of the fourth UDMI periprocedural MI (odds ratio [OR] 1.54, 95% confidence interval [CI]: 1.04-2.27, p = 0.031). CONCLUSIONS: In patients with chronic coronary syndrome undergoing elective PCI, complex PCI is associated with a significantly higher risk of periprocedural MI using multiple definitions. These findings highlight the importance of considering upfront this risk in the planning of complex PCI procedures.

Therapeutic concordance improves blood pressure control in patients with resistant hypertension.

INTRODUCTION: An empathetic approach may be particularly useful in patients with therapy-resistant hypertension (TRH), defined as the failure to achieve target blood pressure (BP) despite a maximal doses of 3 antihypertensive drugs including a diuretic. However, the effects of therapeutic concordance have not been determined in hypertensive patients. METHODS: We designed a study to explore the impact of therapeutic concordance in patients with TRH, who were included in an intervention arm based on a protocol in which trained personnel periodically verified the pharmacological regimen of these patients. RESULTS: From a cohort of 5331 hypertensive patients followed-up for 77.64 ± 34.44 months, 886 subjects were found to have TRH; of these, 322 had apparent TRH (aTRH: uncontrolled office BP but optimal home BP) and 285 refused to participate in a second follow-up study, yielding a population of 279 patients with true TRH (tTRH). These tTRH patients were followed according to the therapeutic concordance protocol for 91.91 ± 54.7 months, revealing that 210 patients (75.27%) remained with uncontrolled BP (uncontrolled tTRH, Group I) while 69 patients (24.73%) reached an optimal BP control (average BP <140/90 mmHg in at least 50% of follow-up visits, Group II). Strikingly, at the end of the second follow-up, the percentage of patients displaying a decline in kidney function was significantly smaller in Group II than in Group I (8.5% vs 23.4%, p < 0.012). CONCLUSIONS: Taken together, our findings indicate for the first time that therapeutic concordance significantly improves the outcome of antihypertensive treatment in a population of patients with TRH.

Dual Antiplatelet Therapy with 3rd Generation P2Y12 Inhibitors in STEMI Patients: Impact of Body Mass Index on Loading Dose-Response.

PURPOSE: This study aims to assess the association between body mass index (BMI) and platelet reactivity in STEMI patients treated with oral 3rd generation P2Y12 inhibitors. METHODS: Overall, 429 STEMI patients were enrolled in this study. Patients were divided into two groups according to BMI (BMI < 25 vs ≥ 25 kg/m2). A propensity score matching (1:1) was performed to balance potential confounders in patient baseline characteristics. Platelet reactivity was assessed by VerifyNow at baseline and after 3rd generation P2Y12 inhibitor (ticagrelor or prasugrel) loading dose (LD). Blood samples were obtained at baseline (T0), 1 h (T1), 2 h (T2), 4-6 h (T3), and 8-12 h (T4) after the LD. High on-treatment platelet reactivity (HTPR) was defined as a platelet reactivity unit value ≥ 208 units. RESULTS: After propensity score matching, patients with BMI ≥ 25 had similar values of baseline platelet reactivity, while they had higher level of platelet reactivity at 1 and 2 h after the LD and higher rate of HRPT. Furthermore, multivariate analysis demonstrated that BMI ≥ 25 was an independent predictor of HTPR at 2 h (OR 2.01, p = .009). Conversely, starting from 4 h after the LD, platelet reactivity values and HRPT rates were comparable among the two study groups. CONCLUSIONS: A BMI ≥ 25 kg/m2 is associated with delayed pharmacodynamic response to oral 3rd generation P2Y12 inhibitor LD, and it is a strong predictor of HTPR in STEMI patients treated by dual antiplatelet therapy with ticagrelor or prasugrel.

Platelet Inhibition with Ticagrelor 60 mg Versus 90 mg Twice Daily in Elderly Patients with Acute Coronary Syndrome: Rationale and Design of the PLINY THE ELDER Trial.

BACKGROUND: Elderly status is steadily increasing among patients with acute coronary syndrome (ACS). Dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 receptor inhibitor is the cornerstone of treatment to prevent recurrent thrombotic complications in patients with ACS. However, DAPT in older patients is challenged by a concurrent heightened risk of ischemia and bleeding. The aim of this study is to evaluate the pharmacodynamic and pharmacokinetic profile of a lower dose of ticagrelor (60 mg twice daily) among elderly patients during the early phase of ACS. STUDY DESIGN: PLINY THE ELDER (PLatelet INhibition with two different doses of potent P2y12 inhibitors in THE ELDERly population) (NCT04739384) is a prospective, randomized, open-label, crossover trial to evaluate the non-inferiority of a lower dose of ticagrelor (60 mg twice daily) compared with a standard dose (90 mg twice daily) among elderly patients with ACS undergoing percutaneous coronary intervention (PCI). A total of 50 patients, aged 75 years or more, with indication to potent P2Y12 receptor inhibitors will be randomized within 3 days from PCI for the index ACS. Patients with indication to oral anticoagulant therapy, treatment with glycoprotein IIb/IIIa inhibitors, or active bleeding will be excluded. The primary endpoint is platelet reactivity determined by P2Y12 reaction units (PRU) (VerifyNow, Accumetrics, San Diego, CA, USA) after treatment with ticagrelor 60 or 90 mg twice daily for 14 days. Secondary endpoints will include other pharmacodynamic tests of ADP-induced aggregation (light transmittance aggregometry and multiple electrode aggregometry) and determination of pharmacokinetic profile (plasma levels of ticagrelor and its metabolite AR-C124910XX) by high performance liquid chromatography-tandem mass spectrometry. CONCLUSIONS: The PLINY THE ELDER trial will determine whether a lower dose of ticagrelor confers non-inferior platelet inhibition compared with the standard dose in the early phase of ACS among elderly patients undergoing PCI, informing future clinical investigation.

Phenanthrene removal from a spent sediment washing solution in a continuous-flow stirred-tank reactor.

The issue of polycyclic aromatic hydrocarbons (PAHs) is widespread in marine sediments involving ecological systems and human health. Sediment washing (SW) has proven to be the most effective remediation approach for sediments polluted by PAHs, such as phenanthrene (PHE). However, SW still raises waste handling concerns due to a considerable amount of effluents generated downstream. In this context, the biological treatment of a PHE- and ethanol-containing spent SW solution can represent a highly efficient and environmentally-friendly strategy, but its knowledge is still scarce in scientific literature and no studies have so far been conducted in continuous mode. Therefore, a synthetic PHE-polluted SW solution was biologically treated in a 1 L aerated continuous-flow stirred-tank reactor for 129 days by evaluating the effect of different pH values, aeration flowrates and hydraulic retention times as operating parameters over five successive phases. A PHE removal efficiency of up to 75-94% was achieved by an acclimated PHE-degrading consortium mainly composed of Proteobacteria, Bacteroidota and Firmicutes phyla through biodegradation following the adsorption mechanism. PHE biodegradation, mainly occurring via the benzoate route due to the presence of PAH-related-degrading functional genes and a phthalate accumulation up to 46 mg/L, was also accompanied by a reduction of dissolved organic carbon and ammonia nitrogen above 99% in the treated SW solution.