Comparison between zofenopril and ramipril in combination with acetylsalicylic acid in patients with left ventricular systolic dysfunction after acute myocardial infarction: results of a randomized, double-blind, parallel-group, multicenter, European study (SMILE-4)

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) are largely employed for treating patients with left ventricular dysfunction (LVD), but their efficacy may be negatively affected by concomitant administration of acetylsalicylic acid (ASA), with some difference among the different compounds. HYPOTHESIS: The interaction between ASA and the two ACEIs zofenopril and ramipril may result in a different impact on survival of cardiac patients, due to differences in the pharmacological properties of the two ACEIs. METHODS: This phase IIIb, randomized, double-blind, parallel-group, multicenter, European study compared the safety and efficacy of zofenopril (60 mg/day) and ramipril (10 mg/day) plus ASA (100 mg/day), in 771 patients with LVD (clinical signs of heart failure or a left ventricular ejection fraction <45%) following acute myocardial infarction (AMI). The primary study end point was 1-year combined occurrence of death or hospitalization for cardiovascular causes. RESULTS: In the intention-to-treat population, the primary outcome was significantly reduced by zofenopril (n = 365) vs ramipril (n = 351) (odds ratio [OR]: 0.70, and 95% confidence interval [CI]: 0.51-0.96; P = 0.028) as a result of a decrease in cardiovascular hospitalization (OR: 0.64,95% CI: 0.46-0.88; P = 0.006). Mortality rate was not significantly different between the 2 treatments (OR: 1.51, 95% CI: 0.70-3.27; P = 0.293). Blood pressure values did not significantly change during the 1-year follow-up. N-terminal pro-brain natriuretic peptide levels were progressively reduced during the study, with no statistically significant between-treatment differences. Proportion of patients with deterioration of renal function during the study was similar between the 2 groups. Drug safety profile was comparable between treatments. CONCLUSIONS: In patients with LVD following AMI, the efficacy of zofenopril associated with ASA was superior to that of ramipril plus ASA, indicating some important clinical implications for the future use of ACEIs in patients with LVD or overt heart failure

Cost effectiveness of zofenopril in patients with left ventricular systolic dysfunction after acute myocardial infarction: a post- hoc analysis of the smile-4 study.

BACKGROUND: In SMILE-4 (the Survival of Myocardial Infarction Long-term Evaluation 4 study), zofenopril + acetylsalicylic acid (ASA) was superior to ramipril + ASA in reducing the occurrence of major cardiovascular events in patients with left ventricular dysfunction following acute myocardial infarction. The present post hoc analysis was performed to compare the cost-effectiveness of zofenopril and ramipril. METHODS: In total, 771 patients with left ventricular dysfunction and acute myocardial infarction were randomized in a double-blind manner to receive zofenopril 60 mg/day (n = 389) or ramipril 10 mg/day (n = 382) + ASA 100 mg/day and were followed up for one year. The primary study endpoint was the one-year combined occurrence of death or hospitalization for cardiovascular causes. The economic analysis was based on evaluation of cost of medications and hospitalizations and was applied to the intention-to-treat population (n = 716). Cost data were drawn from the National Health Service databases of the European countries participating in the study. The incremental cost-effectiveness ratio was used to quantify the cost per event prevented with zofenopril versus ramipril. RESULTS: Zofenopril significantly (P = 0.028) reduced the risk of the primary study endpoint by 30% as compared with ramipril (95% confidence interval, 4%-49%). The number needed to treat to prevent a major cardiovascular event with zofenopril was 13 less than with ramipril. The cost of drug therapies was higher with zofenopril (328.78 Euros per patient per year, n = 365) than with ramipril (165.12 Euros per patient per year, n = 351). The cost related to the occurrence of major cardiovascular events requiring hospitalization averaged 4983.64 Euros for zofenopril and 4850.01 Euros for ramipril. The incremental cost-effectiveness ratio for zofenopril versus ramipril was 2125.45 Euros per event prevented (worst and best case scenario in the sensitivity analysis was 3590.09 and 3243.96 Euros, respectively). CONCLUSION: Zofenopril is a viable and cost-effective treatment for managing patients with left ventricular dysfunction after acute myocardial infarction

3-D Echocardiography Is Feasible and More Reproducible than 2-D Echocardiography for In-Training Echocardiographers in Follow-up of Patients with Heart Failure with Reduced Ejection Fraction

Left ventricular volumes (LVVs) and ejection fraction (LVEF) are key elements in the evaluation and follow-up of patients with heart failure with reduced ejection fraction (HFrEF). Therefore, a feasible and reproducible imaging method to be used by both experienced and in-training echocardiographers is mandatory. Our aim was to establish if, in a large echo lab, echocardiographers in-training provide feasible and more reproducible results for the evaluation of patients with HFrEF when using 3-dimensional echocardiography (3-DE) versus 2-dimensional echocardiography (2-DE). Sixty patients with HFrEF (46 males, age: 58 ± 17 y) underwent standard transthoracic 2-D acquisitions and 3-D multibeat full volumes of the left ventricle. One expert user in echocardiography (expert) and three echocardiographers with different levels of training in 2-DE (beginner, medium and advanced) measured the 2-D LVVs and LVEFs on the same consecutive images of patients with HFrEF. Afterward, the expert performed a 1-mo training in 3-DE analysis of the users, and both the expert and trainees measured the 3-D LVVs and LVEF of the same patients. Measurements provided by the expert and all trainees in echo were compared. Six patients were excluded from the study because of poor image quality. The mean end-diastolic LVV of the remaining 54 patients was 214 ± 75 mL with 2-DE and 233 ± 77 mL with 3-DE. Mean LVEF was 35 ± 10% with 2-DE and 33 ± 10% with 3-DE. Our analysis revealed that, compared with the expert user, the trainees had acceptable reproducibility for the 2-DE measurements, according to their level of expertise in 2-DE (intra-class coefficients [ICCs] ranging from 0.75 to 0.94). However, after the short training in 3-DE, they provided feasible and more reproducible measurements of the 3-D LVVs and LVEF (ICCs ranging from 0.89-0.97) than they had with 2-DE. 3-DE is a feasible, rapidly learned and more reproducible method for the assessment of LVVs and LVEF than 2-DE, regardless of the basic level of expertise in 2-DE of the trainees in echocardiography. In echo labs with a wide range of staff experience, 3-DE might be a more accurate method for the follow-up of patients with HFrEF

Patient perceptions of anticoagulant treatment with dabigatran or a vitamin K antagonist for stroke prevention in atrial fibrillation according to region and age : an exploratory analysis from the RE-SONANCE study

Funding Information: The authors thank all the patients who participated in this study. Medical writing support was provided by Parexel, with funding from Boehringer Ingelheim GmbH. Funding Information: Dragos Vinereanu received grants and personal fees from Boehringer Ingelheim during the conduct of the study; grants and personal fees from Bristol-Myers Squibb, Pfizer, Bayer, Johnson & Johnson, and Daiichi Sankyo outside the submitted work. Dmitry Napalkov received research grants and has participated in scientific advisory boards for Boehringer Ingelheim and has received speaker’s honoraria from Bayer, Boehringer Ingelheim, Pfizer, and Takeda. Bela Benczur received speaker’s/consultancy fees from Bayer, Berlin-Chemie/Menarini, Boehringer Ingelheim, Krka Pharma, Novartis, Pfizer, Sandoz, and Sanofi. Martin Ciernik, Alexey Medvedchikov, and Wenbo Tang are employees of Boehringer Ingelheim. Pentti Põder received educational grants from Boehringer Ingelheim. Maria Trusz-Gluza received personal fees from Boehringer Ingelheim (null during the conduct of the study), personal fees and non-financial support from Boehringer Ingelheim, and personal fees from Bayer outside the submitted work. Jiří Vesely received personal fees and non-financial support from Bayer, Boehringer Ingelheim, Pfizer, MSD, and PRO.MED.CS outside the submitted work. All other authors report no conflicts of interest. Publisher Copyright: © 2021, The Author(s).Background: The oral anticoagulant dabigatran offers an effective alternative to vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF), yet patient preference data are limited. The prospective observational RE-SONANCE study demonstrated that patients with AF, newly initiated on dabigatran, or switching to dabigatran from long-term VKA therapy, reported improved treatment convenience and satisfaction compared with VKA therapy. This pre-specified sub-study aimed to assess the impact of country and age on patients’ perceptions of dabigatran or VKA therapy in AF. Methods: RE-SONANCE was an observational, prospective, multi-national study (NCT02684981) that assessed treatment satisfaction and convenience in patients switching from VKAs to dabigatran (Cohort A), or newly diagnosed with AF receiving dabigatran or VKAs (Cohort B), using the PACT-Q questionnaire. Pre-specified exploratory outcomes: variation in PACT-Q2 scores by country and age (< 65, 65 to < 75, ≥ 75 years) (both cohorts); variation in PACT-Q1 responses at baseline by country and age (Cohort B). Results: Patients from 12 countries (Europe/Israel) were enrolled in Cohort A (n = 4103) or B (n = 5369). In Cohort A, mean (standard deviation) PACT-Q2 score increase was highest in Romania (convenience: 29.6 [23.6]) and Hungary (satisfaction: 26.0 [21.4]) (p < 0.001). In Cohort B, mean (standard error) increase in PACT-Q2 scores between dabigatran and VKAs was highest in Romania (visit 3: 29.0 [1.3]; 24.5 [0.9], p < 0.001). Mean PACT-Q2 score increase by age (all p < 0.001) was similar across ages. PACT-Q1 responses revealed lowest expectations of treatment success in Romania and greatest concerns about payment in Estonia, Latvia, and Romania, but were similar across ages. Conclusions: Treatment satisfaction and convenience tended to favor dabigatran over VKAs. Regional differences in treatment expectations exist across Europe. Trial and clinical registry: Trial registration number: ClinicalTrials.gov NCT02684981. Trial registration date: February 18, 2016.publishersversionPeer reviewe

An atypical case of pulmonary embolism from a jugular vein

Neck venous malformations and their potentially life-threatening complications are rarely reported in the available literature. Cases of aneurysmal or hypo-plastic jugular vein thrombosis associated with systemic embolization have not been frequently reported. We present the case of a 60-year-old male, without any known risk factors for thromboembolic disease, admitted for sudden onset dyspnea. The physical examination was remarkable for a right lateral cervical mass, expanding with Valsalva maneuver. Thoracic CT with contrast established the diagnosis of bilateral pulmonary embolism and raised the suspicion of superior vena cava and right atrial thrombosis. Bedside transthoracic echocardiography confirmed the presence of a large right atrial thrombus, with intermittent protrusion through the tricuspid valve. Systemic thrombolysis with Alteplase was initiated shortly after diagnosis, in parallel with unfractionated heparin, with complete resolution of the intracavitary thrombus documented by echocardiography. The patient showed significant improvement in symptoms and was later started on oral anticoagulation. Computed vascular tomography of the neck was performed before discharge, showing hypoplasia of the left internal jugular vein and aneurismal dilation of the contralateral internal jugular vein, without thrombosis. There were no identifiable systemic causes for thrombosis. Surgical resection of the aneurismal jugular vein was excluded, because of its potential to cause intracranial hypertension. The preferred therapeutic option in this case was long-term oral anticoagulation

The multi-modality cardiac imaging approach to the Athlete's heart: an expert consensus of the European Association of Cardiovascular Imaging

The term 'athlete's heart' refers to a clinical picture characterized by a slow heart rate and enlargement of the heart. A multi-modality imaging approach to the athlete's heart aims to differentiate physiological changes due to intensive training in the athlete's heart from serious cardiac diseases with similar morphological features. Imaging assessment of the athlete's heart should begin with a thorough echocardiographic examination. Left ventricular (LV) wall thickness by echocardiography can contribute to the distinction between athlete's LV hypertrophy and hypertrophic cardiomyopathy (HCM). LV end-diastolic diameter becomes larger (>55 mm) than the normal limits only in end-stage HCM patients when the LV ejection fraction is <50%. Patients with HCM also show early impairment of LV diastolic function, whereas athletes have normal diastolic function. When echocardiography cannot provide a clear differential diagnosis, cardiac magnetic resonance (CMR) imaging should be performed. With CMR, accurate morphological and functional assessment can be made. Tissue characterization by late gadolinium enhancement may show a distinctive, non-ischaemic pattern in HCM and a variety of other myocardial conditions such as idiopathic dilated cardiomyopathy or myocarditis. The work-up of athletes with suspected coronary artery disease should start with an exercise ECG. In athletes with inconclusive exercise ECG results, exercise stress echocardiography should be considered. Nuclear cardiology techniques, coronary cardiac tomography (CCT) and/or CMR may be performed in selected cases. Owing to radiation exposure and the young age of most athletes, the use of CCT and nuclear cardiology techniques should be restricted to athletes with unclear stress echocardiography or CMR

Part One: Extracellular Vesicles as Valuable Players in Diabetic Cardiovascular Diseases

Extracellular vesicles (EVs) are particles released in the extracellular space from all cell types in physiological and pathological conditions and emerge as a new way of cell-cell communication by transferring their biological contents into target cells. The levels and composition of circulating EVs differ from a normal condition to a pathological one, making them real circulating biomarkers. EVs have a very complex contribution in both health and disease, most likely in relationship between diabetes and cardiovascular disease. The involvement of EVs to the development of cardiovascular complications in diabetes remains an open discussion for therapists. Circulating EVs may offer a continuous access path to circulating information on the disease state and a new perspective in finding a correct diagnosis, in estimating a prognosis and also in applying an effective therapy. Besides their role as biomarkers and targets for therapy, EVs can be exploited as biological tools in influencing the different processes affected in diabetic cardiovascular diseases. This chapter will summarize the current knowledge about EVs as biological vectors modulating diabetic cardiovascular diseases, including atherosclerosis, coronary artery disease, and peripheral arterial disease. Finally, we will point out EVs’ considerable value as clinical biomarkers, therapeutic targets, and potential biomedical tools for the discovery of effective therapy in diabetic cardiovascular diseases

Practical use of dabigatran etexilate for stroke prevention in atrial fibrillation.

Atrial fibrillation (AF) is associated with an increased risk of thromboembolism, and is the most prevalent factor for cardioembolic stroke. Vitamin K antagonists (VKAs) have been the standard of care for stroke prevention in patients with AF since the early 1990s. They are very effective for the prevention of cardioembolic stroke, but are limited by factors such as drug-drug interactions, food interactions, slow onset and offset of action, haemorrhage and need for routine anticoagulation monitoring to maintain a therapeutic international normalised ratio (INR). Multiple new oral anticoagulants have been developed as potential replacements for VKAs for stroke prevention in AF. Most are small synthetic molecules that target thrombin (e.g. dabigatran etexilate) or factor Xa (e.g. rivaroxaban, apixaban, edoxaban, betrixaban, YM150). These drugs have predictable pharmacokinetics that allow fixed dosing without routine laboratory monitoring. Dabigatran etexilate, the first of these new oral anticoagulants to be approved by the United States Food and Drug Administration and the European Medicines Agency for stroke prevention in patients with non-valvular AF, represents an effective and safe alternative to VKAs. Under the auspices of the Regional Anticoagulation Working Group, a multidisciplinary group of experts in thrombosis and haemostasis from Central and Eastern Europe, an expert panel with expertise in AF convened to discuss practical, clinically important issues related to the long-term use of dabigatran for stroke prevention in non-valvular AF. The practical information reviewed in this article will help clinicians make appropriate use of this new therapeutic option in daily clinical practice

Part Two: Extracellular Vesicles as a Risk Factor in Neurodegenerative Diseases

Extracellular vesicles (EVs) involved in the intercellular communication hold cell-specific cargos that contain proteins, various species of RNA and lipids. EVs are emerging as powerful tools for diagnosis and therapy in most diseases but little is known about their role in central nervous system (CNS) physiology or disease. Considering the extraordinary intricated cytoarchitecture of the brain, the implication of EVs in its pathophysiology is difficult to establish. Blood circulating EVs derived from local or distant vascular cells or EVs released from brain into the cerebrospinal fluid (CSF) may influence the brain activity. EVs released in the blood stream from various tissues may influence the brain by passing through the blood-brain barrier (BBB) or through choroid plexus. Since the choroid plexus has also a clearance role, it might be possible that EVs carrying brain abnormal proteins to pass into the blood can be detected. Thus, considering that EVs are specialized cargos bearing combined signals between cells, they might be an interesting therapy target in the future for both regulating neurogenesis and abnormal protein clearance. We present here data gathered about EVs that may influence the CNS functionality and be involved in most common neurodegenerative diseases

Nutraceutical approaches to non-alcoholic fatty liver disease (NAFLD): A position paper from the International Lipid Expert Panel (ILEP)

Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10-25% of the general adult population, 15% of children, and even &gt; 50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD). More recently the acronym MAFLD (Metabolic Associated Fatty Liver Disease) has been preferred by many European and US specialists, providing a clearer message on the metabolic etiology of the disease. The suggestions for the management of NAFLD are like those recommended by guidelines for CVD prevention. In this context, the general approach is to prescribe physical activity and dietary changes the effect weight loss. Lifestyle change in the NAFLD patient has been supplemented in some by the use of nutraceuticals, but the evidence based for these remains uncertain. The aim of this Position Paper was to summarize the clinical evidence relating to the effect of nutraceuticals on NAFLD-related parameters. Our reading of the data is that whilst many nutraceuticals have been studied in relation to NAFLD, none have sufficient evidence to recommend their routine use; robust trials are required to appropriately address efficacy and safety