Strike early-strike strong lipid-lowering strategy with PCSK9i in ACS patients. Real-world evidence from AT-TARGET-IT registry.

AIMS: No data are available on early initiation of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in patients with acute coronary syndrome (ACS) in real-world. This study investigates the effects of PCSK9i started at time of ACS hospitalization on lipid control and major CV events in real-world. METHODS: The lipid control outcome was the percentage of patients reaching the LDL-C target of < 55 mg/dL at first lipid control. The clinical outcome was the incidence of composite major CV events (all cause death, non-fatal MI, non-fatal stroke, and ischemia-driven revascularization) during follow-up in relation to quartiles of LDL-C at first lipid control. RESULTS: We included 771 patients with ACS from AT-TARGET-IT registry, receiving PCSK9i prescription during hospitalization or at discharge. Median LDL-C was 137 mg/dL and decreased to 43 mg/dL at first lipid control. 527 (68.3%) patients achieved LDL-C target at the first lipid control at a median time of 37 days from hospitalization; of them, 404 (76.8%) were discharged on statin plus ezetimibe background therapy. Event curves through a median follow-up of 11 months across quartiles of LDL-C showed a stepwise lower risk of 4P-MACE, 3P-MACE, all-cause mortality, and ischemia-driven revascularization in lower quartile of LDL-C values at first lipid control (<23 mg/dL) and in patients reaching LDL-C <55 mg/dL. CONCLUSIONS: Intensive and early lipid-lowering therapy using PCSK9i in patients with ACS (strike early strike strong strategy) is safe and effective in clinical practice and associated with a reduction of residual CV risk.

This study, from AT-TARGET-IT registry, investigates the effects of PCSK9i started at time of ACS hospitalization on lipid control and major CV events in real-world. Intensive and early PCSK9i therapy reduce composite major cardiovascular (CV) events in patients in reaching LDL-C target values. A strike early-strike strong strategy is safe and effective.

Gastric protection in cardiological practice: an Italian survey on the prescriptive attitude.

BACKGROUND: Gastric protection is commonly considered in patients who use medications able to damage gastric mucosa, mainly NSAIDs, antiplatelets, and anticoagulants. Therefore, cardiologists may frequently prescribe drugs to protect the stomach from damaging medications. The present survey investigated the attitude toward using gastric protection by a panel of Italian cardiologists. METHODS: A self-administered questionnaire included three sections concerning practical problems on this issue in clinical practice facing patients with cardiological disorders. The questionnaire was administered in three successive months. RESULTS: Ninety Italian cardiologists completed the questionnaire. They all consider gastric protection, mainly when prescribing potentially noxious medications. Usually, cardiologists prescribe proton pump inhibitors (PPIs) in 60% of their patients. Alginates and mucosal protectors are less considered. As a rule, cardiologists request investigations if the initial treatment fails. Moreover, the safety issue is carefully assessed. Furthermore, this survey experience significantly affected the approach to managing patients who require gastric protection. The participants carefully considered the prescriptive appropriateness of gastric protectors, mainly concerning the PPIs use. Consequently, PPIs were discontinued when inappropriate. A new medical device with triple action (antacid, mucosal protectors, and anti-reflux) contributed to this new attitude. CONCLUSIONS: The present survey underscored that the appropriateness in prescribing gastric protectors is clinically relevant. In addition, a longitudinal survey experience contributed to change the practical approach by highlighting the prescriptive appropriateness of PPIs, and using a new medical device with multiple gastroprotective activities.

Effects on Right Ventricular Function One Year after COVID-19-Related Pulmonary Embolism.

The aim of this study was to investigate the presence of subclinical cardiac dysfunction in recovered coronavirus disease 2019 (COVID-19) patients, who were stratified according to a previous diagnosis of pulmonary embolism (PE) as a complication of COVID-19 pneumonia. Out of 68 patients with SARS-CoV-2 pneumonia followed up for one year, 44 patients (mean age 58.4 ± 13.3, 70% males) without known cardiopulmonary disease were divided in two groups (PE+ and PE-, each comprising 22 patients) and underwent clinical and transthoracic echocardiographic examination, including right-ventricle global longitudinal strain (RV-GLS), and RV free wall longitudinal strain (RV-FWLS). While no significant differences were found in the left- or right-heart chambers' dimensions between the two study groups, the PE+ patients showed a significant reduction in RV-GLS (-16.4 ± 2.9 vs. -21.6 ± 4.3%, p < 0.001) and RV-FWLS (-18.9 ± 4 vs. -24.6 ± 5.12%, p < 0.001) values compared to the PE- patients. According to the ROC-curve analysis, RV-FWLS < 21% was the best cut-off with which to predict PE diagnosis in patients after SARS-CoV-2 pneumonia (sensitivity 74%, specificity 89%, area under the curve = 0.819, p < 0.001). According to the multivariate logistic regression model, RV-FWLS < 21% was independently associated with PE (HR 34.96, 95% CI:3.24-377.09, p = 0.003) and obesity (HR 10.34, 95% CI:1.05-101.68, p = 0.045). In conclusion, in recovered COVID-19 patients with a history of PE+, there is a persistence of subclinical RV dysfunction one year after the acute phase of the disease, detectable by a significant impairment in RV-GLS and RV-FWLS. A reduction in RV-FWLS of lower than 21% is independently associated with COVID-related PE.

An unexpected cause of chest pain, dyspnea and palpitations in a young patient during a post-COVID syndrome.

A 31-year-old male presented with sudden onset of chest pain and dyspnea after a COVID-19 infection. Initially labeled as a myopericarditis related to COVID-19, because of the young age and low risk profile, after a multiparametric evaluation was possible to diagnose and treat an unstable lesion on an intermediate branch of left coronary.

Myocardial Work by Echocardiography: Principles and Applications in Clinical Practice.

Left ventricular (LV) global longitudinal strain (GLS) has established itself in the last decade as a reliable, more objective method for the evaluation of LV systolic function, able to detect subtle abnormalities in LV contraction even in the presence of preserved ejection fraction (EF). However, recent studies have demonstrated that GLS, similar to LV EF, has important load dependency. Non-invasive myocardial work (MW) quantification has emerged in the last years as an alternative tool for myocardial function assessment. This new method, incorporating measurement of strain and LV pressure, has shown to overcome GLS and LV EF limitations and provide a loading-independent evaluation of myocardial performance. The presence of a commercially available echocardiographic software for the non-invasive MW calculation has allowed the application of this new method in different settings. This review sought to provide an overview on the current knowledge of non-invasive MW estimation, showing its potential applications and possible added value in clinical practice.

Improving Adherence to Ticagrelor in Patients After Acute Coronary Syndrome: Results from the PROGRESS Trial.

BACKGROUND: Dual antiplatelet therapy (DAPT) with aspirin and ticagrelor is recommended for at least 12 months in patients after an acute coronary syndrome (ACS). However, its underuse and premature discontinuation are common in clinical practice. We aimed to investigate the impact of a dedicated follow-up strategy with clinical visits and counselling on adherence levels to ticagrelor in patients after ACS. METHODS: PROGRESS (PROmotinG dual antiplatelet therapy adheREnce in the setting of acute coronary Syndromes) is a prospective, randomized trial enrolling 400 ACS patients treated with ticagrelor. Patients were randomized to be followed-up in a dedicated outpatient clinic (In-person follow-up group, [IN-FU], n=200), or with scheduled for phone interviews only (Telephone follow-up group [TEL-FU], n=200), to assess ticagrelor adherence and related complications. DAPT disruption was defined as an interruption of the administration of the drug due to complications or other reasons of non-adherence, and divided according to the duration into short (1-5 days), temporary (6-30 days) and permanent (≥30 days) disruption. The primary endpoint was the rate of DAPT disruption at 1-year follow-up. RESULTS: The rate of ticagrelor disruption at 1 year follow-up was higher in the TEL-FU group than in the IN-FU group (19.6 vs 5.5%; p<0.0001). The IN-FU group reported a significantly lower rate of short (3.0 vs 8.5%; p=0.012) and permanent (2.0 vs 9.6%; p=0.012) disruption than TEL-FU group. The rate of major bleeding did not differ significantly between the 2 groups (p=0.450). CONCLUSION: The PROGRESS trial showed a net reduction in DAPT disruption in patients followed-up with clinical (in-person) follow-up visits in a dedicated outpatient clinic compared with those scheduled for phone interviews only.

Anesthesiological Management in Transcatheter Mitral Valve Repair With MitraClip: Beyond the EVEREST Criteria.

Percutaneous mitral valve repair with the MitraClip system recently emerged as a viable and less invasive therapeutic option in patients with severe mitral regurgitation deemed to be high-risk surgical candidates. Mitral valve morphology and geometry features are key elements for MitraClip eligibility. In the setting of functional mitral regurgitation, the presence of a leaflet coaptation gap due to advanced left ventricle remodeling can be a potential exclusion criterion for MitraClip therapy. In this article, the authors present a case of successful MitraClip implantation in a patient with severe functional mitral regurgitation and a significant coaptation gap. Periprocedural and intraoperative pharmacological and anesthesiological management were fundamental for successful grasping and procedural success.

Safety and Efficacy of Triple Antithrombotic Therapy with Dabigatran versus Vitamin K Antagonist in Atrial Fibrillation Patients: A Pilot Study.

BACKGROUND: Combination of dual antiplatelet (DAPT) and oral anticoagulation therapy is required to decrease cardioembolic stroke and stent thrombosis risk in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS). We compared the safety and efficacy of dabigatran etexilate with vitamin K antagonist (VKA), in combination with DAPT (aspirin plus clopidogrel) treatment in AF patients who underwent percutaneous coronary intervention (PCI) with stenting for ACS. METHODS: Consecutive nonvalvular AF patients who received twice-daily dabigatran 110 mg (n = 389) or VKA (n = 510) and DAPT were included. Primary endpoints were major bleeding (safety) and the composite of ischemic stroke, systemic embolism, and myocardial infarction (efficacy). The secondary efficacy endpoint was hospitalization for cardiovascular disease. RESULTS: After propensity score matching, comparative treatment groups comprised 175 dabigatran recipients and 175 VKA recipients. The cumulative incidence of major bleeding was lower in the dabigatran group (2.3%) compared with the VKA group (10.3%) with a hazard ratio (HR) of 4.81 [95% confidence interval (CI) 1.6-14.2, p < 0.005]. The cumulative incidence of thromboembolic events with dabigatran was slightly higher (8.0%) than with VKA (6.85%), but not statistically significantly so (0.8, 0.39-1.8; p = 0.6). Cumulative incidence of hospitalization for cardiovascular disease was lower with dabigatran (10.3%) compared with VKA (20.6%) treatment (2.2, 1.25-3.8; p < 0.006). CONCLUSION: Dabigatran at the dose used for stroke prevention appears safer than VKA and maintains a similar efficacy profile, when used with DAPT, in AF patients who have undergone PCI with stenting for ACS.

Lomitapide in homozygous familial hypercholesterolemia: cardiology perspective from a single-center experience.

AIMS: Homozygous familial hypercholesterolemia (HoFH) is a genetic dyslipidemia characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C) and accelerated atherosclerosis. Frequently, traditional lipid-lowering therapy is ineffective in these patients, and lipoprotein apheresis is required. Lomitapide has been recently approved for HoFH. We reported our experience in HoFH patients treated with lomitapide, evaluating its efficacy and safety profile. METHODS: Probands suspected for familial hypercholesterolemia were extrapolated from the registry of patients admitted to our cardiology department. Dutch Lipid Clinic Network (DLCN) criteria were adopted to diagnose familial hypercholesterolemia clinically. Individuals receiving a definite or probable diagnosis of familial hypercholesterolemia underwent family cascade screening and genetic test. Patients with a genetic diagnosis of HoFH were treated with lomitapide and monitored with serial follow-up visits. RESULTS: Within 1 year of screening, from a population of 3250 patients admitted to our cardiology department, seven probands were selected with a DLCN score greater than 5. A total of two patients resulted genetically homozygotes for familial hypercholesterolemia and started lomitapide. A marked reduction in LDL-C occurred in both patients on lomitapide (78% reduction in patient 1 and 86% in patient 2 already on lipoprotein apheresis, compared with baseline LDL-C), allowing the apheresis treatment to be stopped in the second case. Lomitapide was well tolerated, and both patients experienced only mild gastrointestinal events. CONCLUSION: Lomitapide is an effective and well tolerated cholesterol-lowering drug approved for the treatment of HoFH patients. It would be useful to administer it early in these patients to reduce LDL-C and avoid the development of fatal cardiovascular complications.

Von Willebrand Factor as a Novel Player in Valvular Heart Disease: From Bench to Valve Replacement.

von Willebrand Factor (vWF) is a well-known mediator of hemostasis and vascular inflammation. Its dynamic modulation in the bloodstream, according to hemodynamic conditions, makes it an appealing biomarker in patients with valvular heart disease (VHD). Recent studies highlight the close connection between vWF and VHD, with possible implications in the pathogenesis of VHD, promoting valve aging and calcification or favoring the development of infective endocarditis. Moreover, vWF has been recently proposed as a new diagnostic and prognostic tool in patients with valve stenosis or regurgitation, showing a strict correlation with severity of valve disease, outcome, and bleeding (Heyde syndrome). A novel role for vWF is also emerging in patients undergoing percutaneous or surgical valve repair/replacement to select and stratify patients, evaluate periprocedural bleeding risk, and detect procedural complications. We also report our single-center experience, suggesting, for the first time, possible clinical implications for vWF in percutaneous mitral valve repair (MitraClip). This review summarizes recent advances in the role of vWF in VHD with an updated overview going from bench to operating room.

The Role of von Willebrand Factor in Vascular Inflammation: From Pathogenesis to Targeted Therapy.

Beyond its role in hemostasis, von Willebrand factor (VWF) is an emerging mediator of vascular inflammation. Recent studies highlight the involvement of VWF and its regulator, ADAMTS13, in mechanisms that underlie vascular inflammation and immunothrombosis, like leukocyte rolling, adhesion, and extravasation; vascular permeability; ischemia/reperfusion injury; complements activation; and NETosis. The VWF/ADAMTS13 axis is implicated in the pathogenesis of atherosclerosis, promoting plaque formation and inflammation through macrophage and neutrophil recruitment in inflamed lesions. Moreover, VWF and ADAMTS13 have been recently proposed as prognostic biomarkers in cardiovascular, metabolic, and inflammatory diseases, such as diabetes, stroke, myocardial infarction, and sepsis. All these features make VWF an attractive therapeutic target in thromboinflammation. Several lines of research have recently investigated "tailor-made" inhibitors of VWF. Results from animal models and clinical studies support the potent anti-inflammatory and antithrombotic effect of VWF antagonism, providing reassuring data on its safety profile. This review describes the role of VWF in vascular inflammation "from bench to bedside" and provides an updated overview of the drugs that can directly interfere with the VWF/ADAMTS13 axis.

Von Willebrand Factor and Cardiovascular Disease: From a Biochemical Marker to an Attractive Therapeutic Target.

BACKGROUND: Despite recent advances, there is still an unmet need in antithrombotic therapy. New drugs have to overcome old targets, looking for new complementary strategies to counteract thrombus formation and propagation. Since its initial recognition in the 50's, von Willebrand Factor (VWF) has proved to be a contributor in clot formation. The contribution of VWF to platelet adhesion and aggregation is pivotal at high shear rates (i.e. microcirculation and critical artery stenosis), where globular-inactive-VWF elongates in a long chain-active conformation. Particularly, at sites of plaque erosion/disruption the activation of VWF may contribute critically to post-stenotic thrombus formation. In this context, VWF is a potential target of antithrombotic therapies. The plasma concentration of VWF increases in high risk population and predicts cardiovascular (CV) outcome. VWF demonstrates an emerging role in different clinical settings; for example, in valvular heart disease where it has been recently proposed as a new fluido-dynamic marker of disease severity and a predictor of successful correction. Drugs used in daily clinical practice (LMWHs, statins, N-acetylcysteine, glycoprotein IIb/IIIa inhibitors) may have an unselective antagonism on the VWF-pathway. Recently, several "tailor-made" inhibitors of VWF have been investigated. In animal models and clinical studies monoclonal antibodies, aptamers and nanobodies have been demonstrated to directly interfere with the VWF pathway. These studies proved the powerful antithrombotic property and the acceptable level of safety of this strategy. CONCLUSION: We provide an overview of the drugs that a have a role in VWF-antagonism, illustrating how they might become a potential option to overcome current limitations of antithrombotic therapy.

From Femoral to Radial Approach in Coronary Intervention.

Since the first cardiac catheterization in 1929, this procedure has evolved considerably. Historically performed via the transfemoral access, in the last years, the transradial access has been spreading gradually due to its many advantages. We have conducted a review of published literature concerning efficacy, safety, and cost-effectiveness, and we analyzed our patients' data, including the results of the recently published Minimizing Adverse hemorrhagic events by TRansradial access site and systemic implementation of angioX (MATRIX) study. This review confirmed the superiority of the transradial access compared to the femoral access, especially regarding complications related to the access site, duration of hospitalization, and comfort for the patient. The transradial approach is an excellent option for coronary angiography, and the procedure's risks are reduced by increased operator experience.

Inflammation and cardiovascular disease: from pathogenesis to therapeutic target.

Atherosclerosis represents the most common pathological substrate of coronary heart disease (CHD), and the characterization of the disease as a chronic low-grade inflammatory condition is now largely accepted. A number of mediators of inflammation have been widely studied, both as surrogate biomarkers and as causal agents, in the pathophysiological network of atherogenesis and plaque vulnerability. The epidemiological observation that biomarkers of inflammation are associated with clinical cardiovascular risk supports the theory that targeted anti-inflammatory treatment appears to be a promising strategy in reducing residual cardiovascular risk on the background of traditional medical therapy. A large number of randomized controlled trials have shown that drugs commonly used in cardiovascular disease (CVD), such as statins, may be effective in the primary and secondary prevention of cardiovascular events through an anti-inflammatory effect. Moreover, several anti-inflammatory drugs are being tested for their potential to reduce residual cardiovascular risk on the background of validated medical therapy for atherosclerotic disease. In this paper, we review relevant evidence with regard to the relationship between inflammation and CVD, from pathogenesis to therapeutic strategies.

Adipose tissue and vascular inflammation in coronary artery disease.

Obesity has become an important public health issue in Western and developing countries, with well known metabolic and cardiovascular complications. In the last decades, evidence have been growing about the active role of adipose tissue as an endocrine organ in determining these pathological consequences. As a consequence of the expansion of fat depots, in obese subjects, adipose tissue cells develope a phenotypic modification, which turns into a change of the secretory output. Adipocytokines produced by both adipocytes and adipose stromal cells are involved in the modulation of glucose and lipid handling, vascular biology and, moreover, participate to the systemic inflammatory response, which characterizes obesity and metabolic syndrome. This might represent an important pathophysiological link with atherosclerotic complications and cardiovascular events. A great number of adipocytokines have been described recently, linking inflammatory mileu and vascular pathology. The understanding of these pathways is crucial not only from a pathophysiological point of view, but also to a better cardiovascular disease risk stratification and to the identification of possible therapeutic targets. The aim of this paper is to review the role of Adipocytokines as a possible link between obesity and vascular disease.

Use and efficacy of saline hydration and N-acetyl cysteine to prevent contrast-induced nephropathy in low-risk populations undergoing coronary artery angiography.

Contrast-induced nephropathy (CIN) is most commonly defined as acute renal failure occurring within 48-72 h of exposure to an intravascular radiographic contrast medium that is not attributable to other causes. In the international literature, a 25% increase in serum creatinine levels or an increase in absolute values of 0.5 mg/dl from baseline has been suggested to define CIN. The reported incidence of CIN varies widely, ranging from 2 to 50%. This variability results from differences in the presence or absence of risk factors. With a retrospective analysis we evaluated the use of saline hydration plus N-acetyl cysteine (NAC) to prevent CIN in a low-risk population of patients undergoing coronary artery angiography compared with an historic low risk group not treated. From January 2009 to December 2009, 152 consecutive patients who underwent coronary artery angiography with a low osmolarity contrast agent were enrolled in our study, and compared with an historic control group consisting of 172 low-risk patients. Nephrotoxic drugs such as diuretics, ACE-I and ARBs were stopped at least 24 h before the procedure. Inclusion criteria to define low-risk population were the absence of: diabetes, age >65 years, or baseline creatinine >1.4 mg/dl. We have treated group A (152 patients, 47.3%) with a saline hydration (1 ml/kg/h) plus N-acetyl cysteine 600 mg 12 h before and 12 h after the procedure; group B (group control of 170 patients, 52.7%) were not treated. The overall incidence of CIN was 7.1% (23 patients). In particular, the incidence of CIN was 2.6% (4 patients) in the group A and 11.2% (19 patients) in the group B (p = 0.002). In the multivariate analysis, including risk factor such as age, hypertension, hypercholesterolemia, current smoking habit baseline creatinine level, contrast index and hydration, the last variable was the only one inversely correlated independently with the incidence of CIN (p = 0.001). In conclusion, intravenous hydration with saline and NAC is an effective and low cost tool in preventing CIN in patients undergoing coronary artery angiography, and, according to the current guidelines, should be used in all high-risk patients for CIN. Our results show that even in patients at low risk, hydration with saline 0.9% plus NAC is useful and significantly reduces the incidence of CIN.