Prognostic significance of the SYNTAX score and SYNTAX score II in patients with myocardial infarction treated with percutaneous coronary intervention.

OBJECTIVES: We aimed to evaluate the prognostic significance of the SYNTAX score (SS) and SYNTAX score II (SS-II) in a contemporary real-world cohort of myocardial infarction (MI) patients treated with percutaneous coronary intervention (PCI). BACKGROUND: The role of SS and SS-II in the prognostic stratification of patients presenting with MI and undergoing PCI has been poorly investigated. METHODS: This study included MI patients treated with PCI from January 2015 to April 2020 at the University Hospital of Salerno. Patients were divided into tertiles according to the baseline SS and SS-II values. The primary outcome measure was all-cause mortality at long-term follow-up; secondary outcome measures were cardiovascular (CV) death and MI. RESULTS: Overall, 915 patients were included in this study. Mean SS and SS-II were 16.1 ± 10.0 and 31.6 ± 11.5, respectively. At propensity weighting adjusted Cox regression analysis, both SS (hazard ratio [HR]: 1.02; 95% confidence interval [CI]: 1.02-1.06; p = 0.017) and SS-II (HR: 1.08; 95% CI: 1.07-1.10; p < 0.001) were significantly associated with the risk of all-cause mortality at long-term follow-up; both SS (HR 1.04; CI 1.01-1.06; p < 0.001) and SS-II (HR 1.08; CI 1.06-1.10; p < 0.001) were significantly associated with the risk of CV death, but only SS-II showed a significant association with the risk of recurrent MI (HR 1.03; CI 1.01-1.05; p < 0.001). At 5 years, SS-II showed a significantly higher discriminative ability for all-cause mortality than SS (area under the curve: 0.82 vs. 0.64; p < 0.001). SS-II was able to reclassify the risk of long-term mortality beyond the SS (net reclassification index 0.88; 95% CI: 0.38-1.54; p = 0.033). CONCLUSIONS: In a real-world cohort of MI patients treated with PCI, SS-II was a stronger prognostic predictor of long-term mortality than SS.

Moving toward Precision Medicine in Acute Coronary Syndromes: A Multimodal Assessment of Non-Culprit Lesions.

Patients with acute coronary syndrome and multivessel disease experience several recurrent adverse events that lead to poor outcomes. Given the complexity of treating these patients, and the extremely high risk of long-term adverse events, the assessment of non-culprit lesions becomes crucial. Recently, two trials have shown a possible clinical benefit into treat non-culprit lesions using a fraction flow reserve (FFR)-guided approach, compared to culprit-lesion-only PCI. However, the most recent FLOW Evaluation to Guide Revascularization in Multivessel ST-elevation Myocardial Infarction (FLOWER-MI) trial did not show a benefit of the use of FFR-guided PCI compared to an angiography-guided approach. Otherwise, intracoronary imaging using optical coherence tomography (OCT), intravascular ultrasound (IVUS), or near-infrared spectroscopy (NIRS) could provide both quantitative and qualitative assessments of non-culprit lesions. Different studies have shown how the characterization of coronary lesions with intracoronary imaging could lead to clinical benefits in these peculiar group of patients. Moreover, non-invasive evaluations of NCLs have begun to take ground in this context, but more insights through adequately powered and designed studies are needed. The aim of this review is to outline the available techniques, both invasive and non-invasive, for the assessment of multivessel disease in patients with STEMI, and to provide a systematic guidance on the assessment and approach to these patients.

Soluble PCSK9 Inhibition: Indications, Clinical Impact, New Molecular Insights and Practical Approach-Where Do We Stand?

Current research on cardiovascular prevention predominantly focuses on risk-stratification and management of patients with coronary artery disease (CAD) to optimize their prognosis. Several basic, translational and clinical research efforts aim to determine the etiological mechanisms underlying CAD pathogenesis and to identify lifestyle-dependent metabolic risk factors or genetic and epigenetic parameters responsible for CAD occurrence and/or progression. A log-linear association between the absolute exposure of LDL cholesterol (LDL-C) and the risk of atherosclerotic cardio-vascular disease (ASCVD) was well documented over the year. LDL-C was identified as the principal enemy to fight against, and soluble proprotein convertase subtilisin kexin type 9 (PCSK9) was attributed the role of a powerful regulator of blood LDL-C levels. The two currently available antibodies (alirocumab and evolocumab) against PCSK9 are fully human engineered IgG that bind to soluble PCSK9 and avoid its interaction with the LDLR. As documented by modern and dedicated "game-changer" trials, antibodies against soluble PCSK9 reduce LDL-C levels by at least 60 percent when used alone and up to 85 percent when used in combination with high-intensity statins and/or other hypolipidemic therapies, including ezetimibe. Their clinical indications are well established, but new areas of use are advocated. Several clues suggest that regulation of PCSK9 represents a cornerstone of cardiovascular prevention, partly because of some pleiotropic effects attributed to these newly developed drugs. New mechanisms of PCSK9 regulation are being explored, and further efforts need to be put in place to reach patients with these new therapies. The aim of this manuscript is to perform a narrative review of the literature on soluble PCSK9 inhibitor drugs, with a focus on their indications and clinical impact.

Secondary Cardiovascular Prevention after Acute Coronary Syndrome: Emerging Risk Factors and Novel Therapeutic Targets.

The control of cardiovascular risk factors, the promotion of a healthy lifestyle, and antithrombotic therapy are the cornerstones of secondary prevention after acute coronary syndrome (ACS). However, many patients have recurrent ischemic events despite the optimal control of traditional modifiable risk factors and the use of tailored pharmacological therapy, including new-generation antiplatelet and lipid-lowering agents. This evidence emphasizes the importance of identifying novel risk factors and targets to optimize secondary preventive strategies. Lipoprotein(a) (Lp(a)) has emerged as an independent predictor of adverse events after ACS. New molecules such as anti-PCSK9 monoclonal antibodies, small interfering RNAs, and antisense oligonucleotides can reduce plasma Lp(a) levels and are associated with a long-term outcome benefit after the index event. The inflammatory stimulus and the inflammasome, pivotal elements in the development and progression of atherosclerosis, have been widely investigated in patients with coronary artery disease. More recently, randomized clinical trials including post-ACS patients treated with colchicine and monoclonal antibodies targeting cytokines yielded promising results in the reduction in major cardiovascular events after an ACS. Gut dysbiosis has also raised great interest for its potential pathophysiological role in cardiovascular disease. This evidence, albeit preliminary and needing confirmation by larger population-based studies, suggests the possibility of targeting the gut microbiome in particularly high-risk populations. The risk of recurrent ischemic events after ACS is related to the complex interaction between intrinsic predisposing factors and environmental triggers. The identification of novel risk factors and targets is fundamental to customizing patient clinical management with a precision medicine perspective.

Lipoprotein(a) levels and risk of adverse events after myocardial infarction in patients with and without diabetes.

INTRODUCTION: The aim of this study was to evaluate the association of lipoprotein(a) [Lp(a)] levels with long-term outcome in patients with recent history of myocardial infarction (MI), and to investigate if diabetes may influence this association. METHODS: Consecutive MI patients who underwent urgent/emergent coronary angiography from February 2013 to June 2019 were prospectively collected. The primary outcome was the composite of MI recurrence and all-cause death. The propensity score weighting technique was used to account for covariates potentially influencing the relationship between Lp(a) levels and the study outcomes. RESULTS: The study population consisted of 1018 post-MI patients (median age 63 years). Diabetes was reported in 280 patients (27.5%), who showed lower Lp(a) levels than patients without diabetes (p = 0.026). At a median follow-up of 1121 days, the primary outcome was reported in 182 patients (17.9%). At univariable Cox regression analysis, Lp(a) was associated with the risk of the primary outcome in the overall population and in non-diabetic patients, but not in diabetics. The adjusted Cox regression analysis confirmed the independent association between Lp(a) values and the primary outcome in non-diabetic patients, but not in diabetics.Lp(a) levels > 70 mg/dL were independently associated with the risk of the primary outcome in non-diabetic patients (adjusted HR: 2.839; 95% CI, 1.382-5.832), but not in diabetics. CONCLUSIONS: In this real-world post-MI population, increasing Lp(a) levels were significantly associated with the risk of recurrent MI and all-cause death, and very high Lp(a) serum concentration independently predicted long-term outcome in non-diabetic patients, but not in diabetics.

COVID-19 and Acute Coronary Syndromes: From Pathophysiology to Clinical Perspectives.

Acute coronary syndromes (ACS) are frequently reported in patients with coronavirus disease 2019 (COVID-19) and may impact patient clinical course and mortality. Although the underlying pathogenesis remains unclear, several potential mechanisms have been hypothesized, including oxygen supply/demand imbalance, direct viral cellular damage, systemic inflammatory response with cytokine-mediated injury, microvascular thrombosis, and endothelial dysfunction. The severe hypoxic state, combined with other conditions frequently reported in COVID-19, namely sepsis, tachyarrhythmias, anemia, hypotension, and shock, can induce a myocardial damage due to the mismatch between oxygen supply and demand and results in type 2 myocardial infarction (MI). In addition, COVID-19 promotes atherosclerotic plaque instability and thrombus formation and may precipitate type 1 MI. Patients with severe disease often show decrease in platelets count, higher levels of d-dimer, ultralarge von Willebrand factor multimers, tissue factor, and prolongation of prothrombin time, which reflects a prothrombotic state. An endothelial dysfunction has been described as a consequence of the direct viral effects and of the hyperinflammatory environment. The expression of tissue factor, von Willebrand factor, thromboxane, and plasminogen activator inhibitor-1 promotes the prothrombotic status. In addition, endothelial cells generate superoxide anions, with enhanced local oxidative stress, and endothelin-1, which affects the vasodilator/vasoconstrictor balance and platelet aggregation. The optimal management of COVID-19 patients is a challenge both for logistic and clinical reasons. A deeper understanding of ACS pathophysiology may yield novel research insights and therapeutic perspectives in higher cardiovascular risk subjects with COVID-19.

Predictors of Recurrent Ischemic Events in Patients With ST-Segment Elevation Myocardial Infarction.

Little is known about the predictors recurrent ischemic events in patients with ST-segment elevation myocardial infarction (STEMI). This study aimed at investigating the predictors of recurrent myocardial infarction (MI) at long-term follow-up in a real-world STEMI cohort. All consecutive STEMI patients who underwent emergent coronary angiography and primary percutaneous coronary intervention between February 2013 and June 2019 at our institution were included. The primary outcome was recurrent MI; secondary outcomes were all-cause death, target vessel revascularization (TVR), in-stent restenosis, definite stent thrombosis (ST) and non-TVR. The study population included 724 STEMI patients; at median follow-up of 803 (324 to 1,394) days, the primary outcome was reported in 70 patients (10.1%). All-cause death occurred in 6.8%, TVR in 4.2%, in-stent restenosis in 2.5%, and ST in 1.9% of cases. At multivariable analysis, diabetes (hazard ratio [HR] = 1.18), serum level of lipoprotein(a) [Lp(a), HR = 1.01], and angiographic evidence of restenotic lesion (HR = 2.98) resulted independent predictors of recurrent MI. Kaplan-Meier analysis confirmed that diabetes, restenotic lesion, and differential Lp(a) risk range values, identified patients with lower long-term survival free from recurrent MI. Lp(a) level ≥ 30 mg/dL had an incremental prognostic stratification capability in patients with diabetes (HR = 5.34), and in patients with both diabetes and restenotic lesion (HR = 17.07). In conclusion, in this contemporary cohort of STEMI patients, diabetes, Lp(a) serum levels and restenotic lesions were independently associated with recurrent MI at long term. The coexistence of Lp(a) level ≥ 30 mg/dL showed an incremental risk stratification capability, supporting its implementation for long-term prognostic assessment in this high-risk clinical setting.

Treatment and Outcome of Patients With Coronary Artery Ectasia: Current Evidence and Novel Opportunities for an Old Dilemma.

Coronary artery ectasia (CAE) is defined as a diffuse or focal dilation of an epicardial coronary artery, which diameter exceeds by at least 1. 5 times the normal adjacent segment. The term ectasia refers to a diffuse dilation, involving more than 50% of the length of the vessel, while the term aneurysm defines a focal vessel dilation. CAE is a relatively uncommon angiographic finding and its prevalence ranges between 0.3 and 5% of patients undergoing coronary angiography. Although its pathophysiology is still unclear, atherosclerosis seems to be the underlying mechanism in most cases. The prognostic role of CAE is also controversial, but previous studies reported a high risk of cardiovascular events and mortality in these patients after percutaneous coronary intervention. Despite the availability of different options for the interventional management of patients with CAE, including covered stent implantation and stent-assisted coil embolization, there is no one standard approach, as therapy is tailored to the individual patient. The abnormal coronary dilation, often associated with high thrombus burden in the setting of acute coronary syndromes, makes the interventional treatment of CAE patients challenging and often complicated by distal thrombus embolization and stent malapposition. Moreover, the optimal antithrombotic therapy is debated and includes dual antiplatelet therapy, anticoagulation, or a combination of them. In this review we aimed to provide an overview of the pathophysiology, classification, clinical presentation, natural history, and management of patients with CAE, with a focus on the challenges for both clinical and interventional cardiologists in daily clinical practice.