Oral Anticoagulation for Atrial Fibrillation in Octogenarians Across the Renal Function Spectrum.

PURPOSE: Our study aimed to describe the efficacy and safety of oral anticoagulation (OAC) use in octogenarians with atrial fibrillation (AF) across the spectrum of renal function. METHODS: Data for this study were sourced from AF Research Database (NCT03760874). AF patients aged ≥ 80 who received OAC treatment, both direct oral anticoagulant (DOAC) and vitamin K antagonist (VKA) were selected. Participants were categorized in 2 groups according to creatinine clearance (CrCl) ≥ 45 and < 45 ml/min/1.73 m2. The primary safety outcome was the occurrence major bleeding. The primary effectiveness outcome was the occurrence of thromboembolic events. RESULTS: A total of 901 AF patients (median age 84 [4.9] years; 44% men) with age ≥ 80 years on treatment with DOACs (n: 629, 70%) and VKA (n: 272, 30%) were included in the study. 303 patients (34%) had CrCl < 45 ml/min/1.73m2 and 598 (66%) had CrCl ≥ 45 ml/min/1.73m2. No significant differences were shown in major bleedings, minor bleedings and thromboembolic events between patients on DOACs vs VKAs, both in the group with CrCl ≥ 45 than < 45 ml/min. In the group with CrCl < 45 ml/min/1.73 m2, a total of 72 patients (23%) died during the follow-up, with higher mortality in VKA group compared to DOACs (45% vs 15%; p < 0.001). At multivariate regression analysis, age [OR: 1.15; p = 0.001] and coronary artery disease (CAD) [OR: 1.74; p = 0.04] were independently associated with mortality; in contrast, the use of DOACs were inversely associated with mortality [OR = 0.26; p < 0.001]. In patients with CrCl ≥ 45 ml/min/1.73 m2, DOACs group experienced less intra-cranial hemorrhage (ICH) (0.2% vs 2.8%; p = 0.01) compared to VKAs. VKAs patients showed higher mortality compared to those on DOACs (29.1% vs 7.9%; p < 0.001). At multivariate regression analysis, chronic heart failure [OR = 2.14; p = 0.01] was independently associated with death, whereas male gender [OR: 0.45; p = 0.009] and the use of DOACs [OR: 0.29; p < 0.001] were associated with lower mortality. CONCLUSION: DOACs seem to be safe and effective in octogenarians with chronic kidney disease at stage ≥ G3b. As compared with VKA administration, the use of DOACs was associated with lower mortality rates among AF octogenarians with renal dysfunction.

Cardiovascular Effects of Weight Loss in Obese Patients with Diabetes: Is Bariatric Surgery the Additional Arrow in the Quiver?

Obesity is an increasingly widespread disease worldwide because of lifestyle changes. It is associated with an increased risk of cardiovascular disease, primarily type 2 diabetes mellitus, with an increase in major cardiovascular adverse events. Bariatric surgery has been shown to be able to reduce the incidence of obesity-related cardiovascular disease and thus overall mortality. This result has been shown to be the result of hormonal and metabolic effects induced by post-surgical anatomical changes, with important effects on multiple hormonal and molecular axes that make this treatment more effective than conservative therapy in determining a marked improvement in the patient's cardiovascular risk profile. This review, therefore, aimed to examine the surgical techniques currently available and how these might be responsible not only for weight loss but also for metabolic improvement and cardiovascular benefits in patients undergoing such procedures.

Improvement of Global Longitudinal Strain and Myocardial Work in Type 2 Diabetes Patients on Sodium-Glucose Cotransporter 2 Inhibitors Therapy.

ABSTRACT: Sodium-glucose cotransporter 2 inhibitors (SGLT2-i) are a novel class of oral hypoglycemic agents currently used among patients with type 2 diabetes mellitus (T2DM). The effects of SGLT2-i inhibitors on cardiac structure and function are not fully understood. The aim of this study is to evaluate the echocardiographic changing among patients with well-controlled T2DM treated with SGLT2-i in real-world setting. Thirty-five well-controlled T2DM patients (65 ± 9 years, 43.7% male) with preserved left ventricular ejection fraction (LVEF) and 35 age and sex-matched controls were included. T2DM patients underwent clinical and laboratory evaluation; 12-lead surface electrocardiogram; 2-dimensional color Doppler echocardiography at enrolment, before SGLT2-i administration, and at 6 months follow-up after an uninterrupted 10 mg once daily of empagliflozin (n: 21) or dapagliflozin (n: 14). Standard echocardiographic measurements, LV global longitudinal strain (LV-GLS), global wasted work, and global work efficiency were calculated. T2DM patients showed higher E\E' ratio (8.3 ± 2.5 vs. 6.3 ± 0.9; P < 0.0001 ) and lower LV-GLS (15.8 ± 8.1 vs. 22.1 ± 1.4%; P < 0.0001 ) and global myocardial work efficiency (91 ± 4 vs. 94 ± 3%; P: 0.0007 ) compared with age and sex-matched controls. At 6-month follow-up, T2DM patients showed a significant increase in LVEF (58.9 ± 3.2 vs. 62 ± 3.2; P < 0.0001 ), LV-GLS (16.2 ± 2.8 vs. 18.7 ± 2.4%; P = 0.003 ), and global work efficiency (90.3 ± 3.5 vs. 93.3 ± 3.2%; P = 0.0004 ) values; conversely, global wasted work values (161.2 ± 33.6 vs. 112.72 ± 37.3 mm Hg%; P < 0.0001 ) significantly decreased. Well-controlled T2DM patients with preserved LVEF who are treated with a SGLT2-i on top of the guidelines direct medical therapy showed a favorable cardiac remodeling, characterized by the improvement of LV-GLS and myocardial work efficiency.

Echocardiographic Features of Cardiac Involvement in Myotonic Dystrophy 1: Prevalence and Prognostic Value.

Myotonic dystrophy type 1 (DM1) is the most common muscular dystrophy in adults. Cardiac involvement is reported in 80% of cases and includes conduction disturbances, arrhythmias, subclinical diastolic and systolic dysfunction in the early stage of the disease; in contrast, severe ventricular systolic dysfunction occurs in the late stage of the disease. Echocardiography is recommended at the time of diagnosis with periodic revaluation in DM1 patients, regardless of the presence or absence of symptoms. Data regarding the echocardiographic findings in DM1 patients are few and conflicting. This narrative review aimed to describe the echocardiographic features of DM1 patients and their prognostic role as predictors of cardiac arrhythmias and sudden death.

Current Views on Infective Endocarditis: Changing Epidemiology, Improving Diagnostic Tools and Centering the Patient for Up-to-Date Management.

Infective endocarditis (IE) is a rare but potentially life-threatening disease, sometimes with longstanding sequels among surviving patients. The population at high risk of IE is represented by patients with underlying structural heart disease and/or intravascular prosthetic material. Taking into account the increasing number of intravascular and intracardiac procedures associated with device implantation, the number of patients at risk is growing too. If bacteremia develops, infected vegetation on the native/prosthetic valve or any intracardiac/intravascular device may occur as the final result of invading microorganisms/host immune system interaction. In the case of IE suspicion, all efforts must be focused on the diagnosis as IE can spread to almost any organ in the body. Unfortunately, the diagnosis of IE might be difficult and require a combination of clinical examination, microbiological assessment and echocardiographic evaluation. There is a need of novel microbiological and imaging techniques, especially in cases of blood culture-negative. In the last few years, the management of IE has changed. A multidisciplinary care team, including experts in infectious diseases, cardiology and cardiac surgery, namely, the Endocarditis Team, is highly recommended by the current guidelines.

Direct Oral Anticoagulants for Stroke Prevention in Special Populations: Beyond the Clinical Trials.

Currently, direct oral anticoagulants (DOACs) are the first-line anticoagulant strategy in patients with non-valvular atrial fibrillation (NVAF). They are characterized by a more favorable pharmacological profile than warfarin, having demonstrated equal efficacy in stroke prevention and greater safety in terms of intracranial bleeding. The study population in the randomized trials of DOACs was highly selected, so the results of these trials cannot be extended to specific populations such as obese, elderly, frail, and cancer patients, which, on the other hand, are sub-populations widely represented in clinical practice. Furthermore, due to the negative results of DOAC administration in patients with mechanical heart valves, the available evidence in subjects with biological heart valves is still few and often controversial. We sought to review the available literature on the efficacy and safety of DOACs in elderly, obese, underweight, frail, cancer patients, and in patients with bioprosthetic heart valves with NVAF to clarify the best anticoagulant strategy in these special and poorly studied subpopulations.

Clinical impact of oral anticoagulation among octogenarians with atrial fibrillation and anaemia.

Our study aimed to describe the efficacy and safety of oral anticoagulation (OAC) use in elderly patients (> or = 80 years-old) with atrial fibrillation (AF) and concomitant anaemia. Data for this study were sourced from AF Research Database (NCT03760874). AF patients aged ≥ 80 who received OAC treatment, both direct oral anticoagulant (DOAC) and vitamin K antagonist (VKA) were selected. Participants were categorized as anaemic and non-anaemic. The primary outcome was the occurrence of overall bleeding. The primary effectiveness outcome was the occurrence of thromboembolic events (a composite of ischemic stroke, transient ischemic attack and systemic embolism). The secondary safety and effectiveness outcomes were major, minor bleedings and mortality, respectively. A total of 958 patients were included in the study, 120 (12.5%) were anaemic; among them, 93 patients (76.6%) were treated with VKAs and 28 (23.3%) with DOAC. Kaplan-Meier curves for major bleedings showed significant differences between anemic- and non-anemic groups (log-rank p = 0.005). In multivariate analysis, among patients on OAC, anaemia was independently associated with major bleeding (HR 2.36; 95% IC 1.2-4.4; p = 0.006), intracranial hemorrhages (HR 3.81; 95% IC 1.35-10.7; p = 0.01) and minor bleedings (HR 2.40; 95%IC 1.1-5.2; p = 0.02); these associations were not confirmed in the DOACs subgroup. No difference in survival was shown between anaemic- and non-anaemic groups and among anaemic patients, between DOAC and VKAs subgroups. Anaemic octogenarians with AF on OAC therapy showed a significantly increased risk of major bleedings, in particular ICH, and mortality compared to non-anaemic.

Impact of previous cardiac function status assessed by echocardiography on the outcome of COVID-19.

More than 91,000 fatalities due to Coronavirus Disease 2019 (COVID-19) have occurred in Spain. Several factors are associated with increased mortality in this disease, including cardiovascular risk factors (CVRF). However, information on the cardiac function of patients prior to the onset of COVID-19 is scarce and the potential impact it may have is uncertain. The aim of the EchoVID study was to describe the potential association between CVRF and cardiac function status prior to SARS-CoV-2 infection and in-hospital mortality. We studied clinical characteristics and cardiac function of patients admitted during the first wave of COVID-19. All patients had a transthoracic echocardiogram performed in the previous 12 months prior to diagnosis; conventional systolic and diastolic function parameters were analyzed. Logistic regression analysis was performed to identify predictors of in-hospital mortality. We included 296 individuals. Median age was higher in the group of patients who died (81.0 vs 76.1 years; p = 0.007). No significant differences were found in CVRF. Survivors were more frequently receiving anticoagulation therapy (52.9% vs 70.8%; p = 0.003). LVEF, although preserved on average in both groups, was significantly lower in the group of deceased patients (56.9% vs 61.1%; p = 0.017). Average E/e' ratio was higher in the deceased group (11.1 vs 10.1; p = 0.049). Five variables were found to be independently associated with in-hospital mortality due to COVID-19: Age, male gender, LVEF, E/e' ratio and anticoagulation therapy. A model including these variables had an area under the ROC curve of 0.756 (CI 0.669-0.843). The echocardiographic variables included in the model significantly improved the discriminative power, compared to a model including only demographic data. Left ventricular ejection fraction and E/e' ratio prior to SARS-CoV-2 infection are two easily-obtained echocardiographic parameters that provide additional prognostic information over clinical factors when assessing patients admitted for SARS-CoV-2 infection.

Optimal anticoagulation in patients with atrial fibrillation and bioprosthetic heart valves.

The antithrombotic management of patients after surgical or transcatheter bioprosthetic heart valves (BHVs) replacement is still challenging. Our review aims to describe the current evidence on the best antithrombotic strategy among patients undergoing BHVs replacement (surgical or transcatheter) and/or valve repair, with particular attention to those with atrial fibrillation.

Prevalence and clinical predictors of inappropriate direct oral anticoagulant dosage in octagenarians with atrial fibrillation.

PURPOSE: Older age is associated with inappropriate dose prescription of direct oral anticoagulants. The aim of our study was to describe the prevalence and the clinical predictors of inappropriate DOACs dosage among octogenarians in real-world setting. METHODS: Data for this study were sourced from the multicenter prospectively maintained Atrial Fibrillation (AF) Research Database (NCT03760874). Of the AF patients aged ≥ 80 who received DOACs treatment, 253 patients were selected. Participants were categorized as appropriate dosage, overdosage, or underdosage. Underdosage and overdosage were, respectively, defined as administration of a lower or higher DOAC dose than recommended in the EHRA consensus. RESULTS: A total of 178 patients (71%) received appropriate DOACs dose and 75 patients (29%) inappropriate DOACs dose; among them, 19 patients (25.6%) were overdosed and 56 (74.4%) were underdosed. Subgroup analysis demonstrated that underdosage was independently associated with male gender [OR = 3.15 (95% IC; 1.45-6.83); p < 0.001], coronary artery disease [OR = 3.60 (95% IC 1.45-9.10); p < 0.001] and body mass index [OR = 1.27 (1.14-1.41); p < 0.001]. Overdosage was independently associated with diabetes mellitus [OR = 18 (3.36-96); p < 0.001], with age [OR = 0.76 (95% IC; 0.61-0.96; p = 0.045], BMI [OR = 0.77 (95% IC; 0.62-0.97; p = 0.043] and with previous bleedings [OR = 6.40 (0.7; 1.43-28); p = 0.039]. There wasn't significant difference in thromboembolic, major bleeding events and mortality among different subgroups. Underdosage group showed a significatively lower survival compared with appropriate dose group (p < 0.001). CONCLUSION: In our analysis, nearly one-third of octogenarians with AF received an inappropriate dose of DOAC. Several clinical factors were associated with DOACs' overdosage (diabetes mellitus type II, previous bleeding) or underdosage (male gender, coronary artery disease, and higher body mass index). Octogenarians with inappropriate DOACs underdosage showed less survival.

Pharmacokinetic determinants for the right dose of antiarrhythmic drugs.

INTRODUCTION: Antiarrhythmic drugs (AADs) show a narrow therapeutic range and marked intersubject variability in pharmacokinetics (PK), which may lead to inappropriate dosing and drug toxicity. AREAS COVERED: The aim of the present review is to describe PK properties of AADs, discussing the main changes in different clinical scenarios, such as the elderly and patients with obese, chronic kidney, liver, and cardiac disease, in order to guide their right prescription in clinical practice. EXPERT OPINION: There are few data about PK properties of AADs in a special population or challenging clinical setting. The use and dose of AADs is commonly based on physicians' clinical experience observing the clinical effects rather than being personalized on the individual patients PK profiles. More and updated studies are needed to validate a patient centered approach in the pharmacological treatment of arrhythmias based on patients' clinical features, including pharmacogenomics, and AAD pharmacokinetics.

Add-on Therapy With Sacubitril/Valsartan and Clinical Outcomes in CRT-D Nonresponder Patients.

ABSTRACT: No data on the add-on sacubitril/valsartan (S/V) therapy among cardiac resynchronization therapy with a defibrillator (CRT-D) nonresponder patients are currently available in literature. We conducted a prospective observational study including 190 CRT-D nonresponder patients with symptomatic heart failure with reduced ejection fraction despite the optimal medical therapy from at least 1 year. The primary endpoint was the rate of additional responders (left ventricular end-systolic volume reduction >15%) at 12 months from the introduction of S/V therapy. At the end of the 12 months follow-up, 37 patients (19.5%) were deemed as "additional responders" to the combination use of CRT + S/V therapy. The only clinical predictor of additional response was a lower left ventricular ejection fraction [OR 0.881 (0.815-0.953), P = 0.002] at baseline. At 12 months follow-up, there were significant improvements in heart failure (HF) symptoms and functional status [New York Heart Association 2 (2-3) vs. 1 (1-2), P < 0.001; physical activity duration/day: 10 (8-12) vs. 13 (10-18) hours, P < 0.001]. Compared with the 12 months preceding S/V introduction, there were significant reductions in the rate of HF rehospitalization (35.5% vs. 19.5%, P < 0.001), in atrial tachycardia/atrial fibrillation burden [6.0 (5.0-8.0) % vs. 0 (0-2.0) %, P < 0.001] and in the proportions of patients experiencing ventricular arrhythmias (21.6% vs. 6.3%; P < 0.001). Our results indicate that S/V add-on therapy in CRT-D nonresponder patients is associated with 19.5% of additional responders, a reduction in HF symptoms and rehospitalizations, AF burden, and ventricular arrhythmias.

The Impact of COVID-19 Pandemic on Hospitalization and Interventional Procedures for Cardiovascular Diseases during the First Wave in Italy.

Coronavirus disease 2019 (COVID-19) has been responsible for an epidemic of devastating proportion, and it has represented a challenge for worldwide healthcare systems with the need of resources reallocation in order to face epidemic spread. Italy was one of the hardest hit countries by COVID-19, and the Italian government adopted strict rules to contain the spread of the COVID-19 pandemic, such as national lockdown and home quarantine; moreover, the Italian healthcare system had to rapidly re-organize the diagnostic and therapeutic pathways, with a reallocation of health resources and hospital beds, in order to manage COVID-19 patients. The aim of the present review is to provide an overview of the effects of the first pandemic wave on cardiovascular assistance in Italy with the purpose of evaluating the strengths and weaknesses of the Italian health system.

Chronic Oral Anticoagulation and Clinical Outcome in Hospitalized COVID-19 Patients.

PURPOSE: The clinical course of COVID-19 may be complicated by acute respiratory distress syndrome (ARDS) and thromboembolic events, which are associated with high risk of mortality. Although previous studies reported a lower rate of death in patients treated with heparin, the potential benefit of chronic oral anticoagulation therapy (OAT) remains unknown. We aimed to investigate the association between OAT with the risk of ARDS and mortality in hospitalized patients with COVID-19. METHODS: This is a multicenter retrospective Italian study including consecutive patients hospitalized for COVID-19 from March 1 to April 22, 2020, at six Italian hospitals. Patients were divided into two groups according to the chronic assumption of oral anticoagulants. RESULTS: Overall, 427 patients were included; 87 patients (19%) were in the OAT group. Of them, 54 patients (13%) were on treatment with non-vitamin k oral anticoagulants (NOACs) and 33 (8%) with vitamin-K antagonists (VKAs). OAT patients were older and had a higher rate of hypertension, diabetes, and coronary artery disease compared to No-OAT group. The rate of ARDS at admission (26% vs 28%, P=0.834), or developed during the hospitalization (9% vs 10%, P=0.915), was similar between study groups; in-hospital mortality (22% vs 26%, P=0.395) was also comparable. After balancing for potential confounders by using the propensity score matching technique, no differences were found in term of clinical outcome between OAT and No-OAT patients CONCLUSION: Oral anticoagulation therapy, either NOACs or VKAs, did not influence the risk of ARDS or death in patients hospitalized with COVID-19.

Edoxaban for the treatment of pulmonary embolism in hospitalized COVID-19 patients.

PURPOSE: We aimed to investigate the clinical performance of edoxaban for the treatment of pulmonary embolism (PE) in hospitalized COVID-19 patients. METHODS: We conducted a retrospective analysis selecting hospitalized patients with COVID-19 admitted to our Institution from 20 May 2020 to 20 November 2020 with computer tomography (CT) detected PE at admission, treated with edoxaban after initial parenteral therapy. Clinical outcomes were compared between patients with and without ARDS at admission and between those with and without CT confirmed PE resolution. RESULTS: 50 patients were included. Mean follow-up was 42.5 ± 10 days. No baseline differences were found between patients with ARDS (30%) and those without ARDS at admission. Patients with PE resolution (84%) were younger (P = 0.03), had a shorter duration of fondaparinux therapy (9.9 ± 3.8 vs 15.8 ± 7.5 days; P = 0.0015) and length of hospitalization (36 ± 8 vs 46 ± 9 days: P = 0.0023) compared with those without PE resolution. 2 patients experienced major bleedings. At multivariate analysis the time to edoxaban switch was the only predictor of the PE resolution (HR: 0.92; 95% C.I. 0.86 to 0.99). CONCLUSION: Edoxaban was an effective and safe treatment for acute PE in COVID-19 setting.

Pharmacokinetics of Direct Oral Anticoagulants in Patients With Atrial Fibrillation and Extreme Obesity.

PURPOSE: Direct oral anticoagulants (DOACs) are recommended in preference to vitamin K antagonists (VKAs) for stroke prevention in patients with atrial fibrillation (AF) eligible for oral anticoagulation therapy; however, data and clinical experiences supporting the use of DOACs in patients with a body mass index ≥40 kg/m2 or weight >120 kg remain limited. The aim of this study was to evaluate the pharmacokinetic properties of DOACs in patients with AF and extreme obesity. METHODS: We enrolled all consecutive patients with AF and extreme obesity undergoing treatment with DOACs followed up at Monaldi Hospital, Naples, Italy. To determine peak plasma and trough levels of DOACs, plasma samples were collected at 2nd, 4th, 6th, and 12th hours from the last dose intake in patients receiving apixaban and dabigatran and at the 2nd, 4th, 6th, and 24th hours in those receiving edoxaban and rivaroxaban. The DOACs' peak and trough plasma levels obtained from our study population were compared with those sourced from pharmacokinetic studies among patients without obesity, defined as a normal reference range in the literature. If at least 1 peak or trough plasma level was found ​​below or above the normal reference ranges, the patients were classified as having out-of-range DOAC plasma levels. Study population was then divided into in-range and out-of-range groups. Baseline characteristics, including DOAC treatment, were compared between the 2 groups. Univariate and multivariate logistic regression analysis were performed to identify baseline variables associated with DOACs' plasma concentration out of the expected range. FINDINGS: A total of 58 patients (mean [SD] age, 70.93 [8.73] years; 40% female) with extreme obesity (mean [SD] body mass index. 44.43 [3.54] kg/m2) and AF while undergoing DOAC treatment were included in the present study. In 9 patients (15.5 %), the DOAC plasma concentrations were out of the expected ranges (out-of-range group);, indicating a greater likelihood of edoxaban 30 mg treatment (33% vs 2%; P < 0.01) and inappropriate DOAC underdosing (56% vs 4%; P < 0.005) compared with the in-range group. According to the multivariate logistic analysis (P = 0.0011), the inappropriate DOAC underdosing (hazard ratio = 29.37; P = 0.0002) was an independent predictor of DOAC plasma levels out of the expected ranges. IMPLICATIONS: Patients with extreme obesity and AF who were receiving DOAC therapy had DOAC plasma concentrations in the expected range. The inappropriate DOAC underdosing seems to be the only independent clinical factor associated with a plasma concentration of the drug out of the expected range.

Left Ventricular Deformation and Vortex Analysis in Heart Failure: From Ultrasound Technique to Current Clinical Application.

Heart failure (HF) is a leading cause of cardiovascular morbidity and mortality. However, its symptoms and signs are not specific or can be absent. In this context, transthoracic echocardiography plays a key role in diagnosing the various forms of HF, guiding therapeutic decision making and monitoring response to therapy. Over the last few decades, new ultrasound modalities have been introduced in the field of echocardiography, aiming at better understanding the morpho-functional abnormalities occurring in cardiovascular diseases. However, they are still struggling to enter daily and routine use. In our review article, we turn the spotlight on some of the newest ultrasound technologies; in particular, analysis of myocardial deformation by speckle tracking echocardiography, and intracardiac flow dynamics by color Doppler flow mapping, highlighting their promising applications to HF diagnosis and management. We also focus on the importance of these imaging modalities in the selection of responses to cardiac resynchronization therapy.

Takotsubo Cardiomyopathy as Epiphenomenon of Cardiotoxicity in Patients With Cancer: A Meta-summary of Case Reports.

ABSTRACT: Many antitumoral drugs have been linked to takotsubo cardiomyopathy, with no clear pathogenetic mechanisms. Data about this condition are lacking in literature. The aim of this meta-summary is to summarize the characteristics of patients with antitumoral drug-induced takotsubo cardiomyopathy, described in case reports available in literature. We searched for published case reports in PubMed, Google Scholar, EMBASE, and Scopus from 2009 about stress cardiomyopathy and antiblastic drugs. We selected 41 case reports. All cases underwent chemotherapy/immunotherapy for different types of cancer. The median age was 58 years, and 61% of them were women. The most common comorbidities were hypertension (12.2%) and dyslipidemia (4.9%), but most of the population had no cardiological clinical history. Takotsubo cardiomyopathy is associated to the 5-fluorouracil (36.5%), capecitabine (9.7%), trastuzumab (9.7%), and immune check point inhibitor (9.7%) treatment. The median time of onset was 2 days (1-150). Cardiogenic shock was the first manifestation in 11 patients (26.8%). Left ventricle ejection fraction recovery was showed in 33 patients (89%) with mean ejection fraction 57.7 ± 7%, after a median of 30-day (4-300) follow-up. Patients with cancer experienced takotsubo cardiomyopathy within few days from the beginning of therapy, and the most of them normalized the heart function in few weeks. Cardiogenic shock showed high prevalence in this setting of patients. Larger studies are needed to better understand the pathological mechanisms of antiblastic drug-induced stress cardiomyopathy, to find risk factors associated and preventive strategies for limit this type of cardiotoxicities.

Edoxaban (LIXIANA®) in the treatment of venous thromboembolism.

Standard therapy for venous thromboembolism (VTE) includes the use of heparins and vitamin K antagonists. Randomized clinical trials have shown that non-vitamin K oral anticoagulants are as effective and safe as standard therapy in VTE treatment, with an improved pharmacological profile. Edoxaban, a direct inhibitor of factor Xa, has demonstrated noninferiority to standard therapy for the treatment of VTE, preserving a high safety profile even in long-term therapy, in frail patients and in severe clinical presentations. The present paper focuses on the role of edoxaban in VTE treatment, from general population to cancer patients, presenting the available data from randomized clinical trials and real world, to discuss edoxaban use in clinical practice.

Clinical Performance of Nonvitamin K Antagonist Oral Anticoagulants in Real-World Obese Patients with Atrial Fibrillation.

The prevalence of both atrial fibrillation (AF) and obesity has steadily increased. Nonvitamin K antagonist oral anticoagulants (NOACs) have been shown to be more effective and safer than vitamin K antagonists (VKAs) for long-term stroke prevention in patients with nonvalvular AF. There are still limited data in the literature regarding performance of NOACs in obese patients with AF in the "real world." The aim of our study was to compare the safety and effectiveness of NOACs versus well-controlled VKA therapy in obese AF patients in a "real-world" setting. Here, we have considered patients with AF and obesity (body mass index [BMI] > 30 kg/m2) on NOAC or VKA therapy included in the multicenter Atrial Fibrillation Research Database (NCT03760874). The occurrence of major bleedings (MBs) and thromboembolic events (composite of ischemic stroke, transient ischemic attack, and systemic embolism) was respectively considered primary safety and effectiveness outcomes. We identified 1,047 AF patients with obesity who received NOAC (n = 272) or VKA (n = 775) treatment. After propensity score matching analysis, 248 NOAC and 496 VKA recipients with similar clinical characteristics, including BMI (34.8 ± 3.4 in NOAC vs. 35.1 ± 3.8 in the VKA group; p = 0.50), were evaluated. The mean follow-up was 39 ± 7 months. The incidence rate of thromboembolic events was 1.10 per 100 person-years (0.67 in NOAC vs. 1.28 in the VKA group; hazard ratio [HR]: 0.52; 95% confidence interval [CI]: 0.22-1.22; p = 0.19). The incidence rate of MB was 1.9 per 100 person-years (1.1 in NOAC vs. 2.28 in the VKA group; HR: 0.46; 95% CI: 0.24-0.88; p = 0.04). The incidence rate of intracranial hemorrhage was 0.4 per 100 person-years (0.27 in NOAC vs. 0.47 in the VKA group; HR: 0.57; 95% CI: 0.12-2.73; p = 0.48). A positive net clinical benefit (NCB) of NOACs over VKAs was found (+0.91). Presence of anemia (HR: 1.75; p = 0.003) and concomitant use of antiplatelet drugs (HR: 2.41; p = 0.001) were found to be independent predictors of MB; moreover, age (HR: 1.65; p = 0.003) was an independent predictor of thromboembolic events. Our data support the hypothesis of safe and effective use of NOACs in patients with AF and obesity, justified by a statistically significant lower incidence of MB and a favorable NCB over VKAs.