Autore/Fonte: Gaetano D’Ambrosio, Damiano Parretti
Razionale di utilizzo dell’acido bempedoico in pazienti intolleranti alle statine
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Novembre 2023
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Autore/Fonte: Gaetano D’Ambrosio, Damiano Parretti
Circulation, Volume 150, Issue Suppl_1, Page A4145821-A4145821, November 12, 2024. Introduction and Background:Arterial dissection during endovascular therapy rarely occurs but can be lethal. A significant blood volume extravasation during coronary artery interventions is related to the very high mortality (20-30%). In this hyperacute emergent clinical situation, covered stents have been considered as a primary measure to prevent further serious arterial events. A fabric-based covered graft stents yield poor clinical outcomes. To overcome these challenges, the balloon-expandable stent with biodegradable film-type graft for treating arterial dissection was invented.Research Questions and Objectives:A novel balloon-expandable stent with biodegradable film graft for overcoming these issues would be valid for efficacy and safety in a rabbit iliac artery dissection model.Method and Approach:Eighteen iliac artery dissections were induced by balloon over-inflation on angiography (Ellis type 2 or 3) and treated using the test device (3.0 x 24 mm). Subsequently, twelve animals underwent histologic examinations and micro-computed tomography (CT) at 0, 2, 4, and 8 weeks and 3, 6, 9, and 12 months and angiography at one-year.Results and Data:There were no adverse cardiovascular events during the one-year. Early-stage histologic examination revealed complete sealing of disrupted vessels by the device, exhibiting mural hematoma, peri-stent red thrombi, and dense infiltration of inflammatory cells. Mid- and long-term histologic examination showed patent stents with neointimal hyperplasia over the stents (% area stenosis: 11.8 at 2weeks, 26.1 at 1month, 29.7 at 3months, 49.2 at 9months, and 51.0 at 1year), along with mild peri-strut inflammatory response (Grade: 1-2 at mid-term and 0-1 at long-term). The graft film became scarcely visible after six months. Both CT and angiography revealed no instances of thrombotic occlusion or in-stent restenosis (% diameter stenosis: 5.7 at 2weeks, 12.3 at 1month, 14.2 at 3months, 25.1 at 9months, and 26.6 at 1 year).Conclusion:The novel balloon-expandable stent with a biodegradable film graft demonstrates feasibility in managing severe artery dissection and preventing lethal vascular events in animal model. Future human studies are warranted to validate these findings and elucidate the clinical outcomes of the study.
Circulation, Volume 150, Issue Suppl_1, Page A4142793-A4142793, November 12, 2024. Background:Despite advances in Second-generation drug-eluting stents (DES), 5-10% of patients still experience in-stent restenosis (ISR) after percutaneous coronary intervention (PCI), which generates significant financial burden and elevates the risk of acute coronary syndrome (ACS) and rehospitalization. Thus, early identification of patients at high risk for ISR is crucial for guiding clinical stratification and early intervention.Aims:To develop and validate a multimodal artificial intelligence (AI) model based on coronary angiography images for predicting ISR risk in patients post-DES implantation.Methods:To establish an accurate predictive model, our approach begins with the pre-training on 100,000 angiographic images to enhance the model’s capability in recognizing image features. Subsequently, we employ the DenseNet architecture as the primary deep learning model, incorporating angiographic images from 2,000 cases of DES-treated de novo lesions—1,000 from patients who did not experience ISR within two years and 1,000 from those who did. A multivariate logistic regression analysis, including radiomic features, clinical baselines, and functional information, constructs the predictive model. Additionally, a separate prospective cohort of 300 cases was assembled for validation to simulate real-world application and to verify the model’s reliability and accuracy.Results:Our study successfully developed an AI prediction model for ISR, utilizing a large cohort of coronary angiography images, which effectively predicts ISR with high accuracy. Leveraging the DenseNet architecture and finely tuned machine learning algorithms, the model achieved a sensitivity and specificity of 90% in the validation cohort. The ROC curve from the test phase demonstrated an AUC above 0.90, underscoring the model’s exceptional diagnostic capabilities. Furthermore, the implementation of this model in a prospective cohort confirmed its reliability and practical utility in real-world clinical settings.Conclusions:This study introduces the first multimodal AI model using angiographic imaging to predict ISR. By demonstrating high diagnostic accuracy and reliability in real-world settings, this model serves as an essential tool for early ISR detection and intervention, ultimately helping to reduce the incidence of major adverse cardiac events (MACEs) and mortality.
Circulation, Volume 150, Issue Suppl_1, Page A4141481-A4141481, November 12, 2024. Background:Upfront two-stent techniques are often used in bifurcation percutaneous coronary interventions (PCI), but there is controversy about optimal strategy selection.Methods:We examined the clinical, angiographic characteristics, and long-term outcomes of 206 bifurcation PCIs using the double kissing (DK) crush or the culotte techniques in 192 patients between 2014-2023 from the Prospective Global Registry for the Study of Bifurcation Lesion Interventions (NCT05100992). For the long-term outcomes adjusted hazard ratios (aHR) and 95% confidence intervals (CI) were calculated using the mixed effects Cox proportional hazards model.Results:DK crush was more commonly used (70.4%). Patients in the culotte group had similar baseline characteristics with the DK crush group. Lesions treated with culotte were more likely to be in the left anterior descending (54.1% vs. 35.9%, p
Circulation, Volume 150, Issue Suppl_1, Page A4138792-A4138792, November 12, 2024. Background:Cardiac Allograft Vasculopathy (CAV) is commonly seen in transplanted hearts. Due to the absence of innervation, many transplanted patients have no symptoms despite extensive disease. This poses a challenge in deciding when to perform coronary interventions. We present a case of significant CAV on surveillance angiogram that posed a challenge in management.Case:A 67-year-old female presented for her fifth surveillance coronary angiography nine and a half years after her heart transplant. The angiogram revealed ostial right coronary artery (RCA) chronic total occlusion (CTO) with left-to-right collaterals as well as diffuse irregularities in the left anterior descending (LAD) and left circumflex arteries. The patient was asymptomatic and two years prior to that, her angiogram revealed no significant disease. Biopsies for the past nine years showed no evidence of allograft rejection. She was subsequently referred for coronary intervention.Due to concern of CTO being a sign of rapidly progressing CAV, it was decided to undergo revascularization of the RCA. Antegrade approach was performed with guidance from contralateral injections. Three overlapping drug-eluting stents were deployed proximally-distally using intravascular ultrasound guidance. Surveillance angiography nine months later showed patent RCA stents with no significant disease otherwise. Eighteen months later, angiography demonstrated CTO of the mid LAD and patent RCA stents with mild in-stent restenosis in the most distal RCA stent. The patient remained asymptomatic.Discussion:CAV develops in fifty percent of transplanted hearts within 10 years and requires close surveillance. In this case, revascularization of the RCA CTO resulted in maintaining graft function for at least two additional years as the development of LAD CTO may have resulted in graft failure had the RCA CTO not been intervened upon. CTO revascularization in CAV has the potential to prolong graft viability and delay the need for re-transplantation. Further studies related to CTO revascularization, especially in asymptomatic transplanted patients, are needed to understand the impact on morbidity and mortality in this patient population.
Circulation, Volume 150, Issue Suppl_1, Page A4146242-A4146242, November 12, 2024. Background:In 2021, the Food and Drug Administration approved the first Photon Counting Computed Tomography (PCCT) system, marking an extraordinary milestone in medical imaging. This advanced technology offers significant advantages in cardiac imaging, particularly in detecting severe calcification lesions and in-stent restenosis (ISR). Subsequently, in October 2023, our hospital became the first to implement a PCCT system. Leveraging the benefits of PCCT, we conducted a study to investigate ISR in patients who had undergone stenting over the course of a year.Methods:From October 2023 to January 2024, all high-risk stented patients, including those with multiple stents, bifurcation lesions, chronic total occlusions, and severe calcification lesions, were included in the study. The PCCT system (tube voltage 120 kV, collimation 120 x 0.2 mm, 50-70 ml Iohexol 300 mg/ml) was utilized to detect ISR. Intra-stent lesions with more than 50% narrowing were classified as ISR. Additionally, the quality of the PCCT images was assessed by two radiology experts using a five-point scale, where 1 indicated excellent quality (absence of artifacts) and 5 indicated non-diagnostic quality (severe artifacts).Results:Eighty patients (77.5% male) met the inclusion criteria, with a mean age of 64.7 ± 10.9 years. Among these patients, 56 had stents in the Left Anterior Descending (LAD) artery, while 27 and 34 had stents in the Left Circumflex Artery (LCx) and Right Coronary Artery (RCA), respectively. In total, 25 patients (31.2%) were identified with ISR. Specifically, ISR was most prevalent in the LCx at 25.9% (7/27), followed by the LAD at 21.4% (12/56), and the RCA at 17.7% (6/34). Nine patients underwent repeat percutaneous coronary intervention (PCI). The overall image quality was rated as excellent, with a median score of 1.5 [IQR, 1-2]. Additionally, 40 patients (50%) had a calcium score over 400.Conclusion:These findings represent the first results obtained using PCCT at our hospital. The results indicated a relatively high rate of ISR, particularly among high-risk patients. Given the excellent image quality, PCCT is a promising technique for the follow-up of patients post-PCI.
Circulation, Volume 150, Issue Suppl_1, Page A4142867-A4142867, November 12, 2024. Aims:Recurrent in-stent restenosis (RISR) refers to a second event of ISR after successful revascularization procedures of an initial ISR lesion. However, due to its unclear pathogenesis, effective treatment methods are lacking in clinical practice. Therefore, this study aims to investigate the potential mechanisms underlying RISR pathogenesis from an immunological perspective using single-cell RNA sequencing (scRNA-seq), to provide theoretical support for clinical interventions.Methods:Single-cell RNA sequencing was conducted to profile coronary blood mononuclear cells (CBMCs) obtained from 10 patients with recurrent in-stent restenosis (RISR) and 10 control individuals without ISR one year after stent implantation. The potential pathogenic pathway was identified through comprehensive bioinformatics analyses and further validated at the cellular level by isolating monocytes via flow cytometry from the coronary blood of patients in the RISR validation cohort (n=8).Results:RISR altered the proportion of monocyte subtypes, including an increasing trend in FCGR3A+ Monos and a decrease in MHC-II+ Monos. And a marked elevation of activator protein-1 (AP-1) complex within monocytes was identified as key contributor to the unique transcript profile observed in RISR. Evidence at both the RNA and protein levels demonstrated that in RISR patients, CCL5 secreted by T cells can specifically interact with CCR1 of monocytes, thereby upregulating the p38 MAPK/AP-1/inflammatory cytokine axis. Furthermore, co-culture experiments revealed that these monocytes with heightened expression of inflammatory cytokines can indeed promote the proliferation and migration of endothelial cells (EC) and smooth muscle cells (SMC), thus contributing to the occurrence and progression of RISR.Conclusion:Our study provides the first depiction of immunological landscape in the coronary blood of RISR patients. The upregulation of the CCR1/p38 MAPK/AP-1/cytokine axis in monocytes is a critical mechanism that facilitates RISR. Our study fills the gap in the understanding of RISR pathogenesis and holds significant implications for guiding clinical interventions.
Circulation, Volume 150, Issue Suppl_1, Page A4146282-A4146282, November 12, 2024. Introduction:Drug-eluting stents (DES) have effectively decreased the incidence of restenosis; however, recent investigations raised the potential for late stent thrombosis (LST). Bioactive stent (BAS) coated with titanium-nitride-oxide has demonstrated favourable outcomes with conflicting results in individuals with acute coronary syndromes. We aimed to outline the comparison of BAS and EES among patients diagnosed with acute coronary syndrome (ACS).Methods:We systematically searched PubMed, Web of Science, Scopus, and Cochrane Central, and EMBASE from inception until February 2024. We included randomised controlled trials (RCTs) and observational studies comparing bioactive titanium-nitric-oxide coated stent stents versus EES stents. The primary outcome was MACE, while secondary outcomes were MI, Cardiac death, All-Cause Death, definite stent thrombosis, and Minimal lumen diameter. All data were pooled as either Mean difference in the random effect model with the corresponding SD or pooled as RR and 95% CI for dichotomous data.Results:Seven RCTs involving 3101 patients were included in the analysis. BAS coated was associated with a reduction in definite stent thrombosis (OR= 0.35, 95% CI [ 0.16 to 0.77], P=0.009), MI (OR= 0.47, 95% CI [ 0.34 to 0.64], P=
Circulation, Volume 150, Issue Suppl_1, Page A4137687-A4137687, November 12, 2024. Background:Rotational atherectomy (RA) has been proven to treat coronary artery calcification (CAC) during percutaneous coronary intervention (PCI). Cutting balloons (CBs) are modified balloons (MB).Purpose:We aim to assess the safety and efficacy of RA followed by CB angioplasty (ROTACUT) before stent placement in CAC.Methods:We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies, which were retrieved by systematically searching PubMed, Web of Science, Scopus, and Cochrane through January 2024. We used Stata version 17 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD), with a 95% confidence interval (CI).Results:We included eight studies with a total of 846 patients. There was no significant difference between ROTACUT and RA + bare balloons in major adverse cardiovascular events (MACE) (RR: 0.60 with 95% CI [0.31, 1.16], P= 0.13), the incidence of cardiac death (RR: 1.32 with 95% CI [0.42, 4.14], P= 0.64), the incidence of target vessel revascularization (TVR) (RR: 1.89 with 95% CI [0.40, 8.84], P= 0.42), the incidence of target lesion revascularization (TLR) (RR: 0.83 with 95% CI [0.39, 1.79], P= 0.64), procedural duration (MD: 0.78 with 95% CI [-4.68, 6.24], P = 0.78), incidence of stent thrombosis (RR: 0.81 with 95% CI [0.22, 2.95], P= 0.75), and the incidence of any procedure-related complications (RR: 0.86 with 95% CI [0.42, 1.75], P= 0.68).Conclusion:ROTACUT and RA + bare balloons demonstrated similar efficacy and safety profiles in terms of MACE, cardiac death, TVR, TLR, procedural duration, stent thrombosis, and all safety outcomes.
Circulation, Volume 150, Issue Suppl_1, Page A4145034-A4145034, November 12, 2024. Background:Revascularization of small vessel coronary artery disease (SvCAD) is still challenging despite the extensive use of drug-eluting stents (DESs), mainly because of an increase in target vessel failure. Drug-coated balloon (DCB) has emerged as an alternative strategy in SvCAD. However, the safety and efficacy of DCB in SvCAD is still controversial. We conducted a meta-analysis comparing the clinical outcomes of DCB and DES in SvCAD patients.Methods:We comprehensively searched the databases of MEDLINE and EMBASE from inception to May 2024. Included studies were published randomized control trials (RCTs) that compared major adverse cardiac events (MACE), target-lesion revascularization (TLR), and target-vessel revascularization (TVR) between DCB and DES in SvCAD patients. Data from each study were combined using the random-effects model.Results:Six RCTs were included in this meta-analysis involving 1,534 SvCAD patients (775 underwent revascularization with DCB and 759 with DES). There was no difference in MACE, TLR, and TVR between DCB and DES groups ([OR] 1.14, 95% CI 0.64-2.00, I 2 =58.2%, p=0.657, [OR] 1.34, 95% CI 0.56-3.23, I 2 =48.5%, p=0.516, and [OR] 1.09, 95% CI 0.59-2.01, I 2 =49.6%, p=0.795, respectively) (Figure 1). There was no publication bias observed in Funnel plot as well as no small-study effect observed in Egger’s test.Conclusions:As compared to DES, our study showed that DCB was associated with similar clinical outcomes and could be a potential alternative strategy in SvCAD patients.
Circulation, Volume 150, Issue Suppl_1, Page A4124070-A4124070, November 12, 2024. Introduction:The most common cause of cardiovascular disease (CVD) is atherosclerosis. The progression of atherosclerosis is characterized by endothelial cell dysfunction, proliferation of smooth muscle cell proliferation, and plaques which lead to progressive arterial stenosis. Bare metal stents (BMS) were developed to hinder stenosis, but re-stenosis has been observed following deployment. Drug-eluting stents (DES) have been developed to mitigate this, by releasing anti-proliferative drugs to suppress smooth muscle cell proliferation. However, these drugs also suppress endothelial growth. To address this, we are developing and evaluating a dual action nanomatrix coated stent comprised of a nitric oxide (NO) releasing peptide amphiphile (PA) and everolimus-encapsulated liposomes to improve endothelial proliferation and suppressing smooth muscle cell proliferation and inflammation.Materials and Methods:The nanomatrix coating contains a PA generated via solid phase peptide synthesis consisting of a nitric oxide donor and a cell adhesive ligand. The everolimus-encapsulated liposomes were prepared with DPPC, DOTAP, DSPE-PEG, and cholesterol via thin film rehydration, followed by encapsulation with everolimus. TEM was performed on liposomes to assess their stability. The release kinetics were evaluated via UV-vis of samples containing released everolimus. To evaluate the dual effect of the nanomatrix coating on metabolism, NO and everolimus were used to treat endothelial and smooth muscle cells, and an MTT assay was done.Results and Discussion:TEM showed that liposomes maintained stability over time. It was found that 60% of everolimus was released by day 30. The MTT assay showed that NO with everolimus increased endothelial cell metabolic activity and maintained or lowered smooth muscle cell activity compared to everolimus alone.Conclusions:Everolimus-encapsulated liposomes have potential as an effective delivery method of everolimus. NO and everolimus have a synergistic effect of improving endothelial function and suppressing smooth muscle cells.
Circulation, Volume 150, Issue Suppl_1, Page A4145990-A4145990, November 12, 2024. Background:Coronary in-stent restenosis (ISR) secondary to neointimal hyperplasia or neoatherosclerosis remains a significant challenge following percutaneous coronary interventions (PCI), with no consensus on the optimal revascularization strategy. We compared the outcome of PCI for ISR using drug-coated balloons (DCB) and drug-eluting stents (DES) and investigated the time trends in their clinical outcomes.Methods:PubMed, Embase, Scopus, and the Cochrane Library databases were searched through May 2024. We included randomized controlled trials (RCTs) comparing DCB versus DES among patients with coronary ISR. The primary outcome was target lesion revascularization (TLR). Secondary outcomes included all-cause mortality, myocardial infarction (MI), stent thrombosis, and late lumen loss (LLL). Random-effects models were employed to analyze outcomes within 1-year and beyond 1-year intervals. Meta-regression analysis was used to investigate the effect of age, sex, history of diabetes, hypertension, dyslipidemia, smoking, and ejection fraction on all outcomes by applying mixed-effect models.Results:We included 10 RCTs (1034 patients in the DCB group and 943 patients in the DES group). We found similar incidence of 1-year TLR (odds ratio [OR] 1.36; 95% confidence interval [CI] 0.86, 2.14;P0.194; I243.3%) and >1-year TLR (OR 0.94; 95% CI 0.57, 1.56;P0.817; I20%) with the use of DCB versus DES. The risks of all-cause mortality, MI, and stent thrombosis were comparable between DCB and DES in 1-year and beyond 1-year follow-ups. At 6-9 months angiographic follow-up, DCB was associated with non-significantly lower LLL compared to DES (standardized mean difference [SMD] -0.12 millimeters; 95% CI -0.29, 0.05;P0.170; I271.7%). Meta-regression indicated that higher prevalence of diabetes was associated with an increased risk of 1-year revascularization after DCB compared to DES (Estimate 0.07;P0.003; I20%). Additionally, male sex was associated with an increased LLL in DCB versus DES (Estimate 0.034;P0.001; I241.8%). No association was found between other baseline characteristics and measured clinical outcomes.Conclusion:DCB demonstrated comparable PCI outcomes compared to DES in patients with coronary ISR.
Circulation, Volume 150, Issue Suppl_1, Page A4139378-A4139378, November 12, 2024. Introduction:The potential benefits and risks of paclitaxel-coated balloon (PCB) angioplasty over uncoated balloon (UB) angioplasty in the management of coronary in-stent restenosis (ISR) is not well established.Hypothesis/Aims:This study aims to determine whether PCB angioplasty is superior to UB angioplasty in patients with coronary ISR in terms of target lesion revascularization (TLR), myocardial infarction (MI), and all-cause mortality rates.Methods:PubMed, Embase and Cochrane Central databases were systematically searched for randomized clinical trials (RCT) comparing PCB with UB angioplasty in patients with coronary ISR. Statistical analyses were performed using Review Manager version 5.4.1. Risk Ratios (RR) with 95% confidence intervals (CI) for dichotomous endpoints were computed with the use of a Mantel-Haenszel random effects model.Results:A total of 1,407 patients from 7 randomized clinical trials were included. Follow-up periods in the included studies ranged from 6 months to 1 year. PCB angioplasty significantly reduced TLR (RR 0.28; 95% CI 0.16-0.48; p
Circulation, Volume 150, Issue Suppl_1, Page A4145223-A4145223, November 12, 2024. Background:This study evaluated the association between elevated levels of Lipoprotein(a) [Lp(a)] and the long-term risk of recurrent ischemic events in patients who underwent percutaneous coronary intervention (PCI), and tracked changes in Lp(a) over time.Methods:The study population was enrolled from the Korea University Guro hospital (KUGH)-PCI registry from January 2004 to January 2018. A total of 5,790 patients (pts) who underwent PCI with drug-eluting stents(DESs), and have been completed clinical follow-up for 5 years. All subjects were divided into two groups according to Lp(a) level; Lp(a)≥50 mg/dL (n=319pts), Lp(a)
Circulation, Volume 150, Issue Suppl_1, Page A4144631-A4144631, November 12, 2024. Background:The rate of in-stent restenosis (ISR) in clinical practice is approximately 5-10% after 5 years of percutaneous coronary intervention for coronary artery disease. ISR is associated with a high risk of adverse events. The current literature comparing drug-eluting stents (DES) to drug-eluting balloons (DEB) for ISR has yielded divergent results, prompting this meta-analysis.Methods:A comprehensive systematic literature review was conducted across major electronic databases, from inception to May 20, 2024. The search was aimed at identifying studies that compared DCB with DES for ISR. Using an inverse-variance random-effects model, we pooled odds ratios (OR) and mean differences (MD) with their respective 95% confidence intervals (CI). Statistical significance was set at p
Circulation, Volume 150, Issue Suppl_1, Page A4134630-A4134630, November 12, 2024. Background:Over 3 million percutaneous coronary interventions (PCI) are performed yearly to treat coronary artery stenosis. Stent thrombosis is a catastrophic complication associated with high morbidity and mortality, and its prevention requires the use of prolonged dual antiplatelet therapy (DAPT), which increases bleeding risk. Within the first 30 days after PCI, the mortality of DAPT-associated major bleeding is on par with recurrent myocardial infarction.Research question:No stent system that provides focal antiplatelet activity to prevent stent thrombosis exists, eliminating the need for systemic DAPT and subsequent bleeding risk.Aim:To address this unmet need, we have developed such a stent, termed “the ticagrelor coated stent” (TCS).Methods:Self-assembled monolayers (SAMs) of 12-aminododecylphosphonic acid (ADPA) were formed on cobalt-chromium stents. The amine tail group of ADPA was used to link the ticagrelor molecule through a Mitsunobu reaction and confirmed via infrared spectroscopy. Coating uniformity was validated via atomic force microscopy. In an ex-vivo porcine arterio-venous fistula model, the ticagrelor-coated stents (TCS) were placed in alternating series adjacent to uncoated bare metal stents (BMS). Similarly, TCS and everolimus-eluting stents were placed in the porcine left circumflex arteries for acute (7 days) and chronic (35 days) studies.Results:(Figure 1): Grossly, no thrombus was seen on the TCS compared to the BMS. Platelet and micro-thrombi adherence were significantly reduced on TCS. Notably, inflammation, measured by neutrophil and monocyte adherence, was also reduced by approximately 10-fold on the TCS vs the BMS. Angiography, optical coherence tomography (OCT), and histopathology results show the TCS widely patent without systemic DAPT.Conclusion:These findings show that TCS prevents stent thrombosis through focal anti-platelet action and may reduce the bleeding risk associated with prolonged use of systemic DAPT. Long-term safety and efficacy studies are underway.