Acute coronary syndromes: hospital management of dyslipidaemia with proprotein convertase subtilisin/kexin 9 inhibitors: time to act.

Atherosclerotic cardiovascular disease (ASCVD) in its countless clinical presentations is, in industrialized countries, the most frequent cause of death and, in recent years, a leading role in the prevention of ASCVD has been attributed to the treatment of dyslipidaemias. If statins and ezetimibe remain the cornerstone of pharmacological treatment, an increasingly relevant role is attributed to the inhibitors of the proprotein convertase subtilisin/kexin 9 (PCSK9i), as a result of the excellent results obtained in their respective trials, not only on the reduction of low-density lipoprotein (LDL) or LDL cholesterol (LDL-C) but also on plaque stabilization and regression. The addition of PCSK9 inhibitors leads to a further reduction in LDL levels and a consequent improvement in prognosis and it is recommended in 'fast-track' administration (intrahospital/discharge) in patients with acute coronary syndromes (ACSs) or multiple cardiovascular events already on statin therapy and LDL >70 mg/dL and in statin-naïve ACS patients and LDL >140 mg/dL. By applying guidelines and fast-track, ∼25% of patients with ACS should receive PCSK9i at discharge but unfortunately patients are currently undertreated.

Antiplatelet therapy in patients with conservatively managed spontaneous coronary artery dissection from the multicentre DISCO registry.

AIMS: The role of antiplatelet therapy in patients with spontaneous coronary artery dissection (SCAD) undergoing initial conservative management is still a matter of debate, with theoretical arguments in favour and against its use. The aims of this article are to assess the use of antiplatelet drugs in medically treated SCAD patients and to investigate the relationship between single (SAPT) and dual (DAPT) antiplatelet regimens and 1-year patient outcomes. METHODS AND RESULTS: We investigated the 1-year outcome of patients with SCAD managed with initial conservative treatment included in the DIssezioni Spontanee COronariche (DISCO) multicentre international registry. Patients were divided into two groups according to SAPT or DAPT prescription. Primary endpoint was 12-month incidence of major adverse cardiovascular events (MACE) defined as the composite of all-cause death, non-fatal myocardial infarction (MI), and any unplanned percutaneous coronary intervention (PCI). Out of 314 patients included in the DISCO registry, we investigated 199 patients in whom SCAD was managed conservatively. Most patients were female (89%), presented with acute coronary syndrome (92%) and mean age was 52.3 ± 9.3 years. Sixty-seven (33.7%) were given SAPT whereas 132 (66.3%) with DAPT. Aspirin plus either clopidogrel or ticagrelor were prescribed in 62.9% and 36.4% of DAPT patients, respectively. Overall, a 14.6% MACE rate was observed at 12 months of follow-up. Patients treated with DAPT had a significantly higher MACE rate than those with SAPT [18.9% vs. 6.0% hazard ratios (HR) 2.62; 95% confidence intervals (CI) 1.22-5.61; P = 0.013], driven by an early excess of non-fatal MI or unplanned PCI. At multiple regression analysis, type 2a SCAD (OR: 3.69; 95% CI 1.41-9.61; P = 0.007) and DAPT regimen (OR: 4.54; 95% CI 1.31-14.28; P = 0.016) resulted independently associated with a higher risk of 12-month MACE. CONCLUSIONS: In this European registry, most patients with SCAD undergoing initial conservative management received DAPT. Yet, at 1-year follow-up, DAPT, as compared with SAPT, was independently associated with a higher rate of adverse cardiovascular events (ClinicalTrial.gov id: NCT04415762).

[Proposal for a diagnostic and therapeutic care pathway of the Piedmont Region on lipid-lowering and antithrombotic treatment in patients with peripheral arterial disease]. / Proposta di percorso diagnostico-terapeutico assistenziale della Regione Piemonte sulla terapia ipolipemizzante ed antitrombotica in pazienti con malattia delle arterie periferiche.

The aim of this paper is to present the diagnostic and therapeutic care pathway on peripheral arterial disease, recently developed in the Piedmont Region, Italy. It proposes a combined approach between the cardiologist and vascular surgeon for optimizing the treatment of patients with peripheral artery disease, which includes the most recently approved antithrombotic and lipid-lowering drugs. The goal is to promote a greater awareness on peripheral vascular disease, in order to implement its treatment patterns and consequently to perform an effective secondary cardiovascular prevention.

Pre-stenting residual thrombotic volume assessed by dual quantitative coronary angiography predicts microvascular obstruction in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

BACKGROUND: Microvascular obstruction (MVO) is a frequent occurrence after primary percutaneous coronary intervention (pPCI), and is associated with adverse left ventricular remodeling and worse clinical outcome. Distal embolization of thrombotic material is one of the most important underlying mechanisms. The aim of this study was to investigate the relation between the thrombotic volume evaluated by dual quantitative coronary angiography (QCA) prior to stenting and the occurrence of MVO as assessed by cardiac magnetic resonance (CMR). METHODS: Forty-eight patients with ST-segment elevation myocardial infarction (STEMI) undergoing pPCI and receiving CMR within 7 days from admission were included. Pre-stenting residual thrombus volume at the site of the culprit lesion was measured by applying automated edge detection and video-assisted densitometry techniques (i.e., dual-QCA), and patients were categorized into tertiles of thrombus volume. The presence of delayed-enhancement MVO, as well as its extent (MVO mass), were assessed by CMR. RESULTS: Pre-stenting dual-QCA thrombus volume was significantly greater in patients with MVO than in those without (5.85 mm3 [2.05-16.71] vs. 1.88 mm3 [1.03-6.92], P=0.009). Patients in the highest tertile showed greater MVO mass compared to those in the mid and lowest tertiles (113.3 gr [0.0-203.8] vs. 58.5 g [0.00-144.4] vs. 0.0 g [0.0-60.225], respectively; P=0.031). The best cut-off value of dual-QCA thrombus volume for prediction of MVO was 2.07 mm3 (AUC: 0.720). The addition of dual-QCA thrombus volume to the traditional angiographic indices of no-reflow enhanced the prediction of MVO by CMR (R=0.752). CONCLUSIONS: Pre-stenting dual-QCA thrombus volume is associated with the presence and extent of MVO detected by CMR in patients with STEMI. This methodology may aid the identification of patients at higher risk of MVO and guide adoption of preventive strategies.

One-year outcomes after transcatheter aortic valve implantation with the latest-generation SAPIEN balloon-expandable valve: the S3U registry.

BACKGROUND: Initial data about the performance of the new-generation SAPIEN 3 Ultra (S3U) valve are highly promising. However, evidence about the longer-term performance and safety of the S3U is scarce. AIMS: We aimed to investigate the 1-year clinical and echocardiographic outcomes of transcatheter aortic valve implantation (TAVI) using the S3U compared with its predecessor, the SAPIEN 3 valve (S3). METHODS: The SAPIEN 3 Ultra registry included consecutive patients who underwent transfemoral TAVI at 12 European centres with the S3U or S3 between October 2016 and December 2020. One-to-one propensity score (PS) matching was performed to account for differences in baseline characteristics. The primary outcomes of interest were all-cause death and the composite of all-cause death, disabling stroke and hospitalisation for heart failure at 1 year. RESULTS: The overall study cohort encompassed 1,692 patients treated with either the S3U (n=519) or S3 (n=1,173). The PS-matched population had a total of 992 patients (496 per group). At 1 year, the rate of death from any cause was 4.9% in the S3U group and 6.3% in the S3 group (p=0.743). Similarly, there were no significant differences in the rates of the primary composite outcome (9.5% in the S3 group and 6.6% in the S3U group; p=0.162). The S3U was associated with lower rates of mild paravalvular leak (PVL) compared with the S3 (odds ratio 0.63, 95% confidence interval: 0.44 to 0.88; p<0.01). No significant differences in transprosthetic gradients were observed between the two groups. CONCLUSIONS: Compared with the S3, the S3U transcatheter heart valve was associated with similar 1-year clinical outcomes but reduced rates of mild PVL.

Impact of Right Ventricular Pacing in Patients With TAVR Undergoing Permanent Pacemaker Implantation.

BACKGROUND: Long-term right ventricular pacing (VP) has been related to negative left ventricular remodeling and heart failure (HF), but there is a lack of evidence regarding the prognostic impact on transcatheter aortic valve replacement (TAVR) patients. OBJECTIVES: The aim of the PACE-TAVI registry is to evaluate the association of high percentage of VP with adverse outcomes in patients with pacemaker implantation after TAVR. METHODS: PACE-TAVI is an international multicenter registry of all consecutive TAVR patients who underwent permanent pacemaker implantation for conduction disturbances in the first 30 days after the procedure. Patients were divided into 2 subgroups according to the percentage of VP (<40% vs ≥40%) at pacemaker interrogation. The primary endpoint was the composite of cardiovascular mortality or hospitalization for HF. RESULTS: A total of 377 patients were enrolled, 158 with VP <40% and 219 with VP ≥40%. After multivariable adjustment, VP ≥40% was associated with a higher incidence of the primary endpoint (HR: 2.76; 95% CI: 1.39-5.51; P = 0.004), first HF hospitalization (HR: 3.37; 95% CI: 1.50-7.54; P = 0.003), and cardiovascular death (HR: 3.77; 95% CI: 1.02-13.88; P = 0.04), while the incidence of all-cause death was not significantly different (HR: 2.17; 95% CI: 0.80-5.90; P = 0.13). Patients with VP ≥ 40% showed a higher New York Heart Association functional class both at 1 year (P = 0.009) and at last available follow-up (P = 0.04) and a nonsignificant reduction of left ventricular ejection fraction (P = 0.18) on 1-year echocardiography, while patients with VP <40% showed significant improvement (P = 0.009). CONCLUSIONS: In TAVR patients undergoing permanent pacemaker implantation, a high percentage of right VP at follow-up is associated with an increased risk for cardiovascular death and HF hospitalization. These findings suggest the opportunity to minimize right VP through dedicated algorithms in post-TAVR patients without complete atrioventricular block and to evaluate a more physiological VP modality in patients with persistent complete atrioventricular block.

"No-Reflow" Phenomenon: A Contemporary Review.

Primary percutaneous angioplasty (pPCI), represents the reperfusion strategy of choice for patients with STEMI according to current international guidelines of the European Society of Cardiology. Coronary no-reflow is characterized by angiographic evidence of slow or no anterograde epicardial flow, resulting in inadequate myocardial perfusion in the absence of evidence of mechanical vessel obstruction. No reflow (NR) is related to a functional and structural alteration of the coronary microcirculation and we can list four main pathophysiological mechanisms: distal atherothrombotic embolization, ischemic damage, reperfusion injury, and individual susceptibility to microvascular damage. This review will provide a contemporary overview of the pathogenesis, diagnosis, and treatment of NR.

[The importance of intensive lipid-lowering therapy after acute coronary syndrome: changing the paradigm to improve the achievement of targets]. / L'importanza di una terapia ipolipemizzante intensiva dopo sindrome coronarica acuta: cambiare il paradigma per migliorare il raggiungimento dei target.

BACKGROUND: Despite the availability of effective lipid-lowering drugs, only few high-risk patients attain their LDL cholesterol (LDL-C) guideline-recommended risk-based goal because of underprescription of combination therapy. We present an 18-month experience with variation of prescription protocols after publication of the 2019 ESC/EAS guidelines for the management of dyslipidemias. METHODS: Overall, 621 consecutive patients hospitalized for acute coronary syndrome at Mauriziano Hospital in Turin, Italy, between January 2020 and June 2021 were enrolled. Lipid-lowering therapy recommended at discharge was registered to evaluate how many patients received statin monotherapy, statin plus ezetimibe combination or triple therapy with high-intensity statin plus ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i). At 6-month follow-up, the reduction in LDL-C, adverse events, compliance and cardiovascular recurrences was analyzed. RESULTS: Of 621 patients enrolled, 7 died during hospitalization. During the entire study period, 33% of patients received statin monotherapy, 50% were discharged on statin-ezetimibe combination, and PCSK9i (evolocumab) was prescribed to 17% of patients. Between April 2020 and June 2021, when new recommendations were introduced into clinical practice, 20% of patients received evolocumab, 56% combination therapy and only 24% were discharged on statin monotherapy. At the beginning of observation, evolocumab was prescribed to 3% of patients hospitalized for acute coronary syndrome, while at the end of the study period 27% of patients were discharged on PCSK9i, with an increase of the prescription rate by 759%; in the same period, prescription of statin monotherapy decreased by 75%. At 6-month follow-up, LDL-C reduction was 77% in patients treated with PCSK9i vs 48% in patients taking statin-ezetimibe combination therapy (p<0.001). All patients on evolocumab reached the guideline-directed goals and a low rate of adverse events was reported, mainly represented by local injection site reactions. Six patients experienced acute coronary syndrome recurrence; only one of them was treated with evolocumab. CONCLUSION: Prescription of intensive lipid-lowering therapy after acute coronary syndrome, eventually with introduction of PCSK9i during hospitalization or at discharge, leads to attainment of guideline-recommended goals for all patients, with a low incidence of adverse events and optimal compliance.

[Use of intravascular ultrasound for the assessment and treatment of left main disease]. / Uso dell'ecografia intravascolare nella valutazione e nel trattamento percutaneo della malattia del tronco comune.

Left main coronary artery (LMCA) disease is a pathological condition of great clinical relevance due to its significant impact on both morbidity and mortality of patients with ischemic heart disease. Due to its bidimensional nature, angiography does not enable an accurate evaluation of the extension, distribution and morphology of LMCA disease. Intravascular ultrasound (IVUS) is the invasive imaging modality of choice for the evaluation of LMCA disease, due to its ability to accurately characterize atherosclerotic disease in all the segments of LMCA bifurcation (including LMCA ostium). IVUS is therefore useful in each step of LMCA procedures: (i) to assess stenosis severity and to evaluate the need for revascularization; (ii) to select the appropriate treatment strategy of LMCA bifurcation (e.g. single vs two stents); (iii) to guide all steps of percutaneous coronary intervention (PCI) (e.g. lesion preparation, decision of the landing zone, stent sizing, proximal optimization, side branch rewiring, kissing balloon); (iv) to optimize stent result (e.g. expansion, apposition, geographical miss, major dissections). Although data obtained from randomized clinical trials are limited, several meta-analyses and registry studies suggest the superiority of IVUS-guided LMCA PCI as compared with LMCA PCI guided by angiography alone in terms of mortality, non-fatal myocardial infarction, stent thrombosis, restenosis, and target lesion revascularization.

Hard Events AfteR Orsiro Sirolimus-Eluting Stent (HEROES) in STEMI: A Multicenter Registry.

OBJECTIVES: To evaluate the safety and efficacy of the Orsiro sirolimus-eluting stent (Biotronik) in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (pPCI). Specific drug-eluting stent (DES) platforms might influence pPCI success rate in the mid-to-long term. Orsiro, a hybrid sirolimus DES with thin struts and a biodegradable polymer, may potentially cause less stent malapposition, stent-induced inflammation, and mechanical damage, improving clinical outcomes. METHODS: We retrospectively enrolled all patients who received 1 or more Orsiro DES in the target vessel of pPCI at 9 Italian centers from January 2012 to March 2016. The primary endpoint was a device-oriented composite endpoint (DOCE) of cardiac death, any myocardial infarction clearly attributable to the intervention culprit vessel (TVMI), and ischemic-driven target-lesion revascularization (ID-TLR) at 1-year follow-up. Secondary endpoints were: (1) DOCE at 6-month and 3-year follow-up; (2) any definite/probable stent thrombosis; and (3) any major bleeding. RESULTS: The study cohort comprised 353 patients. At 1-year follow-up, we observed a 3.7% cumulative incidence of DOCE, consisting of 11 cardiac deaths (3.1%), 2 TVMIs (0.6%), and 2 ID-TLRs (0.6%). There was only 1 definite stent thrombosis (0.3%) and 8 bleedings (2.4%). Kaplan-Meier analysis showed DOCE-free survival rates of 96.6% at 6 months, 96.3% at 1 year, and 93.8% at 3 years. CONCLUSIONS: Our findings support the real-world safety and efficacy of the Orsiro stent for pPCI.

Neoatherosclerosis after drug-eluting stent implantation: a novel clinical and therapeutic challenge.

The recognition that obstructive disease of the epicardial coronary arteries, causing ischaemic heart disease, can be treated with a percutaneous coronary intervention (PCI) has been a major discovery in cardiology in the last 40 years contributing, in particular, to the reduction of mortality associated to acute myocardial infarction (AMI). However, even in the era of drug-eluting stent (DES) implantation, a sizable proportion of patients who undergo PCI may develop late or very late post-implantation complications, that occur in the form of restenosis, neoatherosclerosis, and/or in-stent thrombosis. Such complications are clinically relevant since they can cause AMI and negatively impact on the outcome. The underlying pathophysiological mechanisms are complex but related to inhibition of neointimal proliferation by DES that, on the hand, reduces the rate of in-stent restenosis, but, on the other hand, causes dysfunctional vessel healing, persistent inflammation, platelet activation, and adverse immunological responses. Multiple approaches have been developed or are under evaluation to target DES-related complications including pharmacotherapy, procedure-related imaging methods, novel stent designs, and drug-delivery methods. The aim of this review is to provide an update on the latest preclinical, translational, and clinical pharmacotherapeutic developments in this setting that target novel cellular mechanisms and pathways that might contribute to neoatherosclerosis. Due to the importance of secondary prevention in the reduction of DES-associated complications, this review also provides a short overview of pharmacological agents that are established or currently being investigated in this regard.

Coronary Atherosclerotic Phenotype and Plaque Healing in Patients With Recurrent Acute Coronary Syndromes Compared With Patients With Long-term Clinical Stability: An In Vivo Optical Coherence Tomography Study.

Importance: At one end of the coronary artery disease (CAD) spectrum, there are patients with multiple recurrent acute coronary syndromes (rACS), and at the other end there are those with long-standing clinical stability. Predicting the natural history of these patients is challenging because unstable plaques often heal without resulting in ACS. Objective: To assess in vivo the coronary atherosclerotic phenotype as well as the prevalence and characteristics of healed coronary plaques by optical coherence tomography (OCT) imaging in patients at the extremes of the CAD spectrum. Design, Setting, and Participants: This is an observational, single-center cohort study with prospective clinical follow-up. From a total of 823 consecutive patients enrolled in OCT Registry of the Fondazione Policlinico A. Gemelli-IRCCS, Rome, Italy, from March 2009 to February 2016, 105 patients were included in the following groups: (1) patients with rACS, defined as history of at least 3 acute myocardial infarctions (AMIs) or at least 4 ACS with at least 1 AMI; (2) patients with long-standing stable angina pectoris (ls-SAP), defined as a minimum 3-year history of stable angina; and (3) patients with a single unheralded AMI followed by a minimum 3-year period of clinical stability (sAMI). Data were analyzed from January to August 2018. Exposures: Intracoronary OCT imaging of nonculprit coronary segments. Main Outcomes and Measures: Coronary plaque features and the prevalence of healed coronary plaques in nonculprit segments as assessed by intracoronary OCT imaging. Results: Of 105 patients, 85 were men (81.0%); the median (interquartile range) age was 68 (63-75) years. Median (interquartile range) time of clinical stability was 9 (5.0-15.0) years in the ls-SAP group and 8 (4.5-14.5) years in the sAMI group. Patients in the rACS and sAMI groups showed similar prevalence of lipid-rich plaque and thin-cap fibroatheroma, which was significantly higher than in those with ls-SAP (lipid-rich plaque 80.0% [n = 24 of 30] vs 76.3% [n = 29 of 38] vs 37.8% [n = 14 of 37], respectively; P < .001; thin-cap fibroatheroma 40.0% [n = 12 of 30] vs 34.2% [n = 13 of 38] vs 8.1% [n = 3 of 37], respectively; P = .006). Spotty calcifications were more frequently observed in patients with rACS than in those with ls-SAP and sAMI (70.0% [n = 21 of 30] vs 40.5% [n = 15 of 37] vs 44.7% [n = 17 of 38], respectively; P = .04). Healed coronary plaques were rarely observed in patients with rACS, whereas their prevalence was significantly higher in patients with ls-SAP and sAMI (3.3% [n = 1 of 30] vs 29.7% [n = 11 of 37] vs 28.9% [n = 11 of 38], respectively; P = .01). Conclusions and Relevance: Patients with rACS have a distinct atherosclerotic phenotype compared with those with ls-SAP, including higher prevalence of thin-cap fibroatheroma and lower prevalence of healed coronary plaques, suggesting that atherosclerotic profile and plaque healing may play a role in leading the natural history of patients with CAD.

Dual quantitative coronary angiography accurately quantifies intracoronary thrombotic burden in patients with acute coronary syndrome: Comparison with optical coherence tomography imaging.

BACKGROUND: Dual quantitative coronary angiography (QCA) has been recently tested for assessment of intracoronary thrombus volume in experimental models. The present study aimed to validate dual QCA in vivo for the assessment of thrombus burden by exploring the correlations between dual QCA-thrombus volume and optical coherence tomography (OCT)-derived indices of thrombotic burden. METHODS AND RESULTS: Fifty-one patients with ACS and angiographic evidence of thrombus undergoing OCT of the culprit lesion before stenting were included. Dual QCA-thrombus volume was calculated as difference between edge-detection and video-densitometry area functions along the target segment. Culprit lesion was categorized using the Ambrose's and AHA/ACC angiographic classifications. Thrombus volume (mean thrombus area × thrombus length), thrombus burden [(mean thrombus area/mean lumen area) x100] and Prati thrombus score (number of quadrants with thrombus) were measured by OCT, and the presence of plaque rupture (PR) or intact fibrous cap (IFC) was assessed. Dual QCA-thrombus volume correlated significantly with OCT-thrombus volume (R = 0.791), thrombus burden (R = 0.767) and Prati thrombus score (R = 0.600) (all p < 0.001). Dual-QCA thrombus volume was significantly higher in patients with PR compared with those with IFC (3.48 mm3 [1.45-11.26] vs. 1.69 mm3 [0.09-5.02], p = 0.013). Compared with IFC, PR showed higher prevalence of eccentric type II Ambrose lesion (41.7% vs. 7.4%, p = 0.004), complex B2/C lesion (87.5% vs. 55.6%, p = 0.012), and heavy calcification (29.2% vs. 3.7%, p = 0.013). CONCLUSIONS: Dual QCA analysis appears to be a promising tool for quantification of intracoronary thrombus in vivo. This novel methodology may be useful to guide intracoronary thrombus removal during percutaneous coronary intervention and to aid prognostic stratification in patients with ACS.