Achievement of target LDL-cholesterol level in patients with acute coronary syndrome undergoing percutaneous coronary intervention: The JET-LDL registry.

BACKGROUND: In patients with acute coronary syndromes (ACS), current guidelines recommend a low-density lipoprotein cholesterol (LDL-C) level < 1.4 mmol/L (<55 mg/dL). METHODS: The JET-LDL is a multicenter, observational, prospective registry created to investigate levels of LDL-C in consecutive patients with ACS undergoing PCI at 35 Italian hospitals, and to report their lipid lowering therapies (LLT). Follow-up was planned at 1 and 3 months. LDL-C reduction >50% from baseline or level < 55 mg/dL at 1-month was the primary endpoint. RESULTS: A total of 1095 patients were included: median age was 67 (58-75); 33.7% were already on LLT. Baseline LDL-C levels was 105 (76.5-137) mg/dL. At hospital discharge all patients were on LLT: 98.1% received statins (as mono or combination therapy), ezetimibe and PCSK9i were used in 60.1% and 8.5% of cases, respectively. Primary endpoint was achieved in 62% (95% CI 58-65) of cases. At 1-month LDL-C levels dropped to 53 (38-70) mg/dL (p < 0.001 vs baseline) and it was <55 mg/dL in 53% (95% CI 49-57) of patients; however, PCSK9i were added to 7 further cases. At 3-months 58% (95% CI 55-62) of patients achieved the target level, but PCSK9i was added to only 11 new patients. CONCLUSIONS: In this real-world registry of ACS patients undergoing PCI, recommend LDL-C levels were obtained in 62% of patients, but PCSK9i prescription was limited to 10% of cases. As LLT pattern appeared mainly improved at hospital discharge, an early and strong treatment should be considered.

Prognostic Impact of Drug-Coated Balloons in Patients With Diabetes Mellitus: A Propensity-Matched Study.

Patients with diabetes mellitus (DM) are at higher risk of restenosis and stent thrombosis after percutaneous coronary intervention (PCI) and drug-eluting stent (DES) positioning. Whether drug-coated balloons (DCB) can offer any benefit in this subset of patients has been seldom cleared out and was the aim of the present propensity-matched cohort study, that compared the prognostic impact of DCB versus DES in patients with DM who underwent PCI. Patients with DM enrolled in the NOvara-BIella-TREnto (NOBITRE) Registry were identified and matched according to propensity score, to a control population of patients with DM treated with DES. The primary study end point was the occurrence of major adverse cardiovascular events (MACEs). A total of 150 patients were identified in the DCB group and matched with 150 DES-treated patients. Patients treated with DCB displayed more often a previous cardiovascular history and received a more complete pharmacological therapy. Target vessel diameter and the percentage of stenosis were lower in patients with DCB, whereas binary in-stent restenosis was more common (p <0.001, p = 0.003, and p <0.001, respectively). Paclitaxel-eluting balloon represented the most common strategy in the DCB group, whereas Zotarolimus-eluting stents were used in half of the DES population. At a median follow-up of 545.5 days, MACE occurred in 54 (19.4%) of patients, with no difference according to the PCI strategy (21.6% vs 17.3%, adjusted hazard ratio [95% confidence interval] 1.51 [0.46 to 4.93], p = 0.50). Major ischemic end points were slightly increased in patients treated with DCB, whereas overall death was significantly reduced (3.6% vs 10.9%; adjusted hazard ratio [95% confidence interval] 0.27 [0.08 to 0.91], p = 0.03). In conclusion, the present propensity-matched study shows that, in patients with DM who underwent PCI for in-stent restenosis or de novo lesions, the use of DCB is associated with a similar rate of MACE and a modest increase in target lesion failure, but a significantly improved survival as compared with DES.

Impact of age on pre-procedural TIMI flow in STEMI patients undergoing primary percutaneous coronary intervention.

BACKGROUND: Advanced age is a major determinant of impaired prognosis among patients with ST-segment elevation myocardial infarction (STEMI). However, the mechanisms associated with suboptimal reperfusion and enhanced complications are still largely undefined. The aim of the present study was to assess the impact of age on the angiographic findings and the procedural results of primary percutaneous coronary intervention (pPCI) in patients with STEMI. METHODS: A consecutive cohort of patients admitted for STEMI treated with pPCI were included. Infarct-related artery (IRA) patency was defined for preprocedural TIMI flow 3. RESULTS: We included 520 patients, divided according to age tertiles (<61; 61-72; ≥73). Elderly patients were more often females, with hypertension, renal failure, prior myocardial infarction or PCI, with lower rates of smoking history, haemoglobin, leukocytes and cholesterol (P < 0.001), lower ejection fraction (P = 0.02), higher use of renin angiotensin system inhibitors, statins, ASA, calcium antagonists, diuretics and beta blockers. At angiography, for the IRA, percentage of thrombus (P = 0.02) and stenosis (P = 0.01), direct stenting (P = 0.02) and glycoprotein IIb-IIIa inhibitors (P = 0.04) inversely related with age, but for higher restenosis (P = 0.04). IRA patency was more common in patients aged ≥73 years (27.9% vs. 32.3% vs. 41.1%, P = 0.01). The impact of age on preprocedural TIMI flow was confirmed at multivariate analysis [adjusted odds ratio (95% confidence interval) = 0.68 (0.47-0.98), P = 0.04]. CONCLUSION: The present study shows that among STEMI patients undergoing primary PCI, more advanced age represents an independent predictor of preprocedural IRA patency. Future studies will define the implications on procedural results and long-term prognosis.

Managing Congenital Heart Defects in Elderly: The Platypnea-Orthodeoxia Syndrome in Underestimated Patent Foramen Ovale.

The platypnea-orthodeoxia syndrome (POS) is a rare and often suboptimally managed condition with a complex diagnostic workup, conversely displaying an easy treatment and a good recovery of symptoms, especially if consequent to an intracardiac shunt. However, its identification is challenging, due to the several clinical manifestations, the multiple etiologies, representing often the delayed presentation of a congenital heart disease. We present a case report and review of available literature on patients with the POS secondary to a patent foramen ovale successfully treated with its closure.

Drug Coated Balloon in the Treatment of De Novo Coronary Artery Disease: A Narrative Review.

Drug coated balloons (DCBs) are currently indicated in guidelines as a first choice option in the management of instant restenosis, whereas their use in de novo lesions is still debated. The concerns raised after the contrasting results of the initial trials with DCBs in de novo lesions have been more recently overcome by a larger amount of data confirming their safety and effectiveness as compared to drug-eluting stents (DES), with potentially greater benefits being achieved, especially in particular anatomical settings, as in very small or large vessels and bifurcations, but also in selected subsets of higher-risk patients, where a 'leave nothing behind' strategy could offer a reduction of the inflammatory stimulus and thrombotic risk. The present review aims at providing an overview of current available DCB devices and their indications of use based on the results of data achieved so far.

Optimization of the pharmacological therapy in patients with poly-vascular disease: A multidisciplinary approach.

The recent shift of the concept of cardiovascular disease as a chronic progressive condition, potentially involving multiple districts, has driven attention to the optimal management of patients with concomitant coronary and peripheral artery disease, representing a subset of patients with an increased risk of events and impaired survival. Recent pharmacological achievements in terms of antithrombotic therapy and lipid-lowering drugs allow multiple therapeutical combinations, thus requiring optimizing the treatment in a tailored fashion according to patients' risk profiles. Nevertheless, data dedicated to this specific subset of patients are still modest. We summarize currently available strategies and indications for the management of antithrombotic and lipid-lowering drugs in patients with the poly-vascular disease.

Long-Term Outcomes With Drug-Eluting Balloon for the Treatment of In-Stent Restenosis and De Novo Lesions: The Novara-Biella-Trento (NOBITRE) Registry.

Drug-coated balloons (DCBs) have emerged for percutaneous coronary interventions (PCI) of in-stent restenosis or particular anatomical subsets. We provide a real-world analysis of the prognostic determinants and long-term outcomes of patients treated with DCB for any lesion in a comprehensive multicenter registry. The primary study endpoint was the occurrence of major cardiovascular events (MACE: composite of all-cause death, myocardial infarction, and target vessel revascularization) at the longest available follow-up. We included 267 patients (196 treated for in-stent restenosis and 71 for de novo lesions), with a median follow-up of 616 [368-1025] days. MACE occurred in 70 (26.2%) of the patients and related with higher rates of in-stent restenosis (P = .04), longer and more type C lesions (P = .05 and P = .04). At multivariate Cox-regression, type C lesions emerged as the only independent predictor of MACE (adjusted OR [95% CI] = 1.83[1.13-2.97], P = .014), mainly driven by target vessel revascularization (adjusted OR[95% CI] = 1.78[1.05-2.95], P = .03) not conditioning survival. In-stent restenosis emerged as major determinant of TLF (adjusted OR[95% CI] = 2.59[1.17-5.75], P = .02). DCBs represent a treatment option for any lesion; however, type C and restenotic lesions are associated with an increased risk of MACE and target lesion failure, where the optimal strategies for patients' selection and lesion preparation are still undefined.

Lipoprotein associated- phospholipase A2 in STEMI vs. NSTE-ACS patients: a marker of cardiovascular atherosclerotic risk rather than thrombosis.

The precise role of Lipoprotein associated phospholipase A2 (Lp-PlA2) in the pathogenesis of acute coronary syndromes (ACS) and in the prediction of future cardiovascular events is still debated. So far, few data exist on the variations of Lp-PlA2 activity in ACS and especially in NSTE-ACS vs. STEMI patients, where thrombotic and atherosclerotic mechanisms could play a differential role. The aim of the present study was, then, to compare Lp-PlA2 activity according to the type of ACS presentation. METHODS: A consecutive cohort of patients undergoing coronary angiography for acute coronary syndrome (ACS) were included and divided according to presentation for non ST-segment elevation-ACS or ST-segment elevation Myocardial Infarction (STEMI). Lp-PLA2 activity was assessed in blood samples drawn at admission using the Diazyme Lp-PlA2 Activity Assay. RESULTS: We included in our study 117 patients, of whom 31 (26.5%) presented with STEMI. STEMI patients were significantly younger (p = 0.05), displayed a lower rate of hypertension (p = 0.002), previous MI (p = 0.001) and PCI (p = 0.01) and used less frequently statins (p = 0.01) and clopidogrel (p = 0.02). White blood cells and admission glycemia were increased in STEMI (p = 0.001, respectively). The prevalence and severity of CAD was not different according to ACS types, but for a higher prevalence of thrombus (p < 0.001) and lower TIMI flow (p = 0.002) in STEMI. The levels of Lp-PlA2 were significantly lower in STEMI as compared to NSTE-ACS patients, (132 ± 41.1 vs. 154.6 ± 40.9 nmol/min/mL, p = 0.01). In fact, the rate of patients with Lp-PlA2 above the median (148 nmol/min/mL) was significantly lower in STEMI patients as compared to NSTE-ACS (32.3% vs. 57%, p = 0.02, adjusted OR[95% CI] = 0.20[0.06-0.68], p = 0.010). Moreover, a direct linear relationship was observed between Lp-PlA2 and LDL-C (r = 0.47, p < 0.001), but not with inflammatory biomarkers. CONCLUSION: The present study shows that among ACS patients, the levels of Lp-PlA2 are inversely associated with STEMI presentation and thrombotic coronary occlusion, being instead increased in NSTE-ACS patients, therefore potentially representing a marker of more aggressive chronic cardiovascular disease with an increased risk of recurrent cardiovascular events.

Coronary Physiology: Modern Concepts for the Guidance of Percutaneous Coronary Interventions and Medical Therapy.

Recent evidence on ischemia, rather than coronary artery disease (CAD), representing a major determinant of outcomes, has led to a progressive shift in the management of patients with ischemic heart disease. According to most recent guidelines, myocardial revascularization strategies based on anatomical findings should be progressively abandoned in favor of functional criteria for the guidance of PCI. Thus, emerging importance has been assigned to the assessment of coronary physiology in order to determine the ischemic significance of coronary stenoses. However, despite several indexes and tools that have been developed so far, the existence of technical and clinical conditions potentially biasing the functional evaluation of the coronary tree still cause debates regarding the strategy of choice. The present review provides an overview of the available methods and the most recent acquirements for the invasive assessment of ischemia, focusing on the most widely available indexes, fractional flow reserve (FFR) and instant-wave free ratio (iFR), in addition to emerging examples, as new approaches to coronary flow reserve (CFR) and microvascular resistance, aiming at promoting the knowledge and application of those "full physiology" principles, which are generally advocated to allow a tailored treatment and the achievement of the largest prognostic benefits.

OCT guided vs. COmplete pci in patieNts with sT segment elevation myocArdial infarCtion and mulTivessel disease: OCT-CONTACT RCT.

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI), percutaneous coronary intervention (PCI) of the culprit lesion significantly reduces the risk of cardiovascular death. However, the management of non-culprit lesions in patients with the multivessel disease remains a matter of debate in this setting. It's still unclear if a morphological OCT-guided approach, identifying coronary plaque instability, may provide a more specific treatment compared with a standard angiographic/functional approach. METHODS: OCT-Contact is a prospective, multicenter, open-label, non-inferiority randomized controlled trial. Patients with STEMI with successful primary PCI of the culprit lesion will be enrolled after the index PCI. Patients will be deemed eligible if a critical coronary lesion other than the culprit (associated with a diameter of stenosis ≥50%) will be identified during the index angiography. Patients will be randomized in a 1:1 fashion to OCT-guided PCI of non-culprit lesions (Group A) vs. complete PCI (Group B). PCI in group A will be undertaken according to criteria of plaque vulnerability, while in group B the use of fractional flow reserve will be left at the operators' discretion. Major-adverse cardiovascular events (MACE) are a composite of all-cause mortality, non-fatal myocardial infarction (MI) (excluding peri-procedural MI), unplanned revascularization, and NYHA IV heart failure) will be the primary efficacy outcome. Single components of MACE along with cardiovascular mortality will be the secondary endpoints. . Safety endpoints will embrace worsening of renal failure, procedural complications, and bleedings. Patients will be followed for 24 months after randomization. RESULTS: A sample size of 406 patients (203 per group) is required to provide the analysis an 80% power to detect a non-inferiority in the primary endpoint with an alpha error set at 0.05 and a non-inferiority limit of 4%. CONCLUSIONS: A morphological OCT-guided approach may be a more specific treatment compared with the standard angiographic/functional approach in non-culprit lesions of STEMI patients.

Impact of renal failure and high-platelet reactivity on major cardiovascular ischemic events among patients with acute coronary syndrome receiving dual antiplatelet therapy with ticagrelor.

BACKGROUND: No study has so far evaluated the impact of chronic kidney disease (CKD) on high-on treatment platelet reactivity (HRPR) with ticagrelor and their prognostic consequences, that were therefore the aim of the present study. METHODS: Patients on dual antiplatelet therapy with ASA+ticagrelor (90mg/twice a day) after percutaneous coronary revascularization for ACS were scheduled for platelet function assessment 30-90 days post-discharge. The primary study endpoint was defined as the occurrence of major cardiovascular events (a composite of cardiovascular death, recurrent acute coronary syndrome (MI), target vessel revascularization) at the longest available follow-up. RESULTS: We included 396 patients, that were divided according to CKD (eGFR

Antithrombotic Strategy in Secondary Prevention for High-Risk Patients with Previous Acute Coronary Syndrome: Overlap between the PEGASUS Eligibility and the COMPASS Eligibility in a Large Multicenter Registry.

BACKGROUND: Patients with previous acute coronary syndrome (ACS) are at high risk of recurrent adverse cardiovascular events. Recently, prolonged dual antiplatelet therapy (DAPT) and oral anticoagulation therapy (OAT) have been shown to reduce recurrent ischemic events to the expense of an increase in bleeding events. The number of patients potentially eligible for these therapies in real life remains to be determined. METHODS: Among ACS patients from five registries and one randomized controlled trial, we assessed the proportion of patients eligible for the PEGASUS strategy only and the proportion of patients eligible for the COMPASS strategy only, and set out the proportion of patients with an overlap between the strategies. FINDINGS: Among the 10,048 evaluable patients, we found that 5373 (53.4%) were eligible for the PEGASUS strategy and 3841 (38.2%) were eligible for the COMPASS strategy, with a group of 3444 (34.4%) overlapping between the two strategies. The number of patients eligible for the PEGASUS strategy only was 1929 (19.2%) and the number eligible for the COMPASS strategy only was 397 (4.0%); 4278 (42.6%) were eligible for neither a PEGASUS strategy nor a COMPASS strategy. INTERPRETATION: In a large cohort of ACS patients, one in three patients was eligible for either a prolonged DAPT with ticagrelor 60 mg and low-dose aspirin or a dual pathway inhibition approach with rivaroxaban 2.5 mg and low-dose aspirin.

Symptoms-to-emergency-call timing delay in acute coronary syndrome before and during COVID-19: independent predictors and their impact on mortality.

BACKGROUND: The COVID-19 pandemic severely impacted global health. The aim of this study was to compare predictors of symptoms-to-emergency-call timing delay in acute coronary syndrome (ACS) and their impact on mortality before and during the COVID-19 outbreak. METHODS: We collected sociodemographic, clinical data, procedural features, preadmission and intra-hospital outcomes of consecutive patients admitted for ACS in seventeen Italian centers from March to April 2018, 2019, and 2020. RESULTS: In 2020, a 32.92% reduction in ACS admissions was observed compared to 2018 and 2019. Unstable angina, typical and atypical symptoms, and intermittent angina were identified as significant predictors of symptoms-to-emergency-call timing delay before and during the COVID-19 pandemic (P<0.005 for all the items). Differently from 2018-2019, during the pandemic, hypertension and dyspnea (P=0.002 versus P=0.490 and P=0.001 vs. P=0.761 for 2018-2019 and 2020, respectively) did not result as predictors of delay in symptoms-to-emergency-call timing. Among these predictors, only the atypical symptoms (HR 3.36; 95% CI: 1.172-9.667, P=0.024) in 2020 and the dyspnea (HR 2.64; 95% CI: 1.345-5.190, P=0.005) in 2018-2019 resulted significantly associated with higher mortality. Finally, the family attendance at the onset of the symptoms resulted in a reduction in symptoms-to-emergency-call timing (in 2020 P<0.001; CI: -1710.73; -493.19) and in a trend of reduced mortality (HR 0.31; 95% CI: 0.089-1.079, P=0.066) in 2020. CONCLUSIONS: During the COVID-19 outbreak, atypical symptoms and family attendance at ACS onset were identified, respectively, as adverse and favorable predictors of symptoms-to-emergency-call timing delay and mortality.

Low levels of vitamin D and coronary artery disease: Is it time for therapy?

The association between vitamin D and the prevalence and severity of coronary artery disease (CAD), major established cardiovascular risk factors, and acute ischemic events has been consistently demonstrated in large-scale observational studies and meta-analyses, with relevant prognostic implications. The rise in prevalence of hypovitaminosis D in recent years, reaching pandemic pro-portions, has pointed to the importance of the identification and optimization of the indications and strategies for the therapeutic use of vitamin D, with particular relevance for cardiovascular health. However, vitamin D supplementation has provided so far inconsistent results in primary prevention, with even fewer data reported in patients with established CAD. The present review aims to provide an updated overview of the available evidence and potential therapeutic applications of vitaminD in patients with CAD.

The Incidence and Impact of In-Hospital Bleeding in Patients with Acute Coronary Syndrome during the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic increased the complexity of the clinical management and pharmacological treatment of patients presenting with an Acute Coronary Syndrome (ACS). AIM: to explore the incidence and prognostic impact of in-hospital bleeding in patients presenting with ACS before and during the COVID-19 pandemic. METHODS: We evaluated in-hospital Thrombolysis In Myocardial Infarction (TIMI) major and minor bleeding among 2851 patients with ACS from 17 Italian centers during the first wave of the COVID-19 pandemic (i.e., March-April 2020) and in the same period in the previous two years. RESULTS: The incidence of in-hospital TIMI major and minor bleeding was similar before and during the COVID-19 pandemic. TIMI major or minor bleeding was associated with a significant threefold increase in all-cause mortality, with a similar prognostic impact before and during the COVID-19 pandemic. CONCLUSIONS: the incidence and clinical impact of in-hospital bleeding in ACS patients was similar before and during the COVID-19 pandemic. We confirmed a significant and sizable negative prognostic impact of in-hospital bleeding in ACS patients.

Safety and Efficacy of Selective, Clopidogrel-Based Strategies in Acute Coronary Syndrome: A Study-Level Meta-analysis.

OBJECTIVES: To investigate outcomes with selective, clopidogrel-based therapies versus conventional treatment in patients undergoing percutaneous coronary intervention (PCI), especially for acute coronary syndrome. BACKGROUND: Safety and efficacy of alternative, selective, clopidogrel-based therapies after PCI are not robustly established. METHODS: We performed a study-level meta-analysis on six randomized trials investigating selective clopidogrel-based therapies (three on unguided de-escalation, N = 3,473; three on guided clopidogrel therapy, N = 7,533). Control groups received ticagrelor or prasugrel treatment. Main endpoints were major bleeding, any bleeding, major adverse cardiovascular events (MACE), and net clinical endpoint. RESULTS: The incidence of major bleeding and MACE was similar in the selective, clopidogrel-based therapy versus the conventional treatment arm (odds ratio [OR]: 0.72, 95% confidence interval [CI]: 0.51-1.01, p = 0.06; OR: 0.93, 0.72-1.20, p = 0.58; respectively). The rates of any bleeding were lower in the selective, clopidogrel-based therapy versus conventional treatment group (OR: 0.57, 95% CI: 0.40-0.80, p = 0.001); this greater safety was significant for unguided de-escalation (OR: 0.43, 95% CI: 0.32-0.58, p = 0.00001) and nonsignificant for guided clopidogrel therapy (OR: 0.72, 95% CI: 0.51-1.02, p = 0.07; p for interaction: 0.03). The incidence of the net clinical endpoint was fewer in the selective, clopidogrel-based therapy versus the conventional treatment arm (OR: 0.59, 95% CI: 0.41-0.85, p = 0.004); this benefit was significant for unguided de-escalation (OR: 0.50, 95% CI: 0.39-0.64, p < 0.00001) and nonsignificant for guided clopidogrel therapy (OR 0.85, 95% CI: 0.62-1.16, p = 0.30; p for interaction: 0.01). CONCLUSION: As compared with prasugrel/ticagrelor treatment, alternative, selective, clopidogrel-based approaches provide a similar protection from cardiovascular events, reduce the risk of any bleeding, and are associated with a greater net benefit. These beneficial effects were prevalent with unguided de-escalation to clopidogrel.

Predictors of Mortality and Cardiovascular Outcome at 6 Months after Hospitalization for COVID-19.

Clinical outcome data of patients discharged after Coronavirus disease 2019 (COVID-19) are limited and no study has evaluated predictors of cardiovascular prognosis in this setting. Our aim was to assess short-term mortality and cardiovascular outcome after hospitalization for COVID-19. A prospective cohort of 296 consecutive patients discharged after COVID-19 from two Italian institutions during the first wave of the pandemic and followed up to 6 months was included. The primary endpoint was all-cause mortality. The co-primary endpoint was the incidence of the composite outcome of major adverse cardiac and cerebrovascular events (MACCE: cardiovascular death, myocardial infarction, stroke, pulmonary embolism, acute heart failure, or hospitalization for cardiovascular causes). The mean follow-up duration was 6 ± 2 months. The incidence of all-cause death was 4.7%. At multivariate analysis, age was the only independent predictor of mortality (aHR 1.08, 95% CI 1.01-1.16). MACCE occurred in 7.2% of patients. After adjustment, female sex (aHR 2.6, 95% CI 1.05-6.52), in-hospital acute heart failure during index hospitalization (aHR 3.45, 95% CI 1.19-10), and prevalent atrial fibrillation (aHR 3.05, 95% CI 1.13-8.24) significantly predicted the incident risk of MACCE. These findings may help to identify patients for whom a closer and more accurate surveillance after discharge for COVID-19 should be considered.