Cardiovascular toxicities of immune therapies for cancer - a scientific statement of the Heart Failure Association (HFA) of the ESC and the ESC Council of Cardio-Oncology.

The advent of immunological therapies has revolutionized the treatment of solid and haematological cancers over the last decade. Licensed therapies which activate the immune system to target cancer cells can be broadly divided into two classes. The first class are antibodies that inhibit immune checkpoint signalling, known as immune checkpoint inhibitors (ICIs). The second class are cell-based immune therapies including chimeric antigen receptor T lymphocyte (CAR-T) cell therapies, natural killer (NK) cell therapies, and tumour infiltrating lymphocyte (TIL) therapies. The clinical efficacy of all these treatments generally outweighs the risks, but there is a high rate of immune-related adverse events (irAEs), which are often unpredictable in timing with clinical sequalae ranging from mild (e.g. rash) to severe or even fatal (e.g. myocarditis, cytokine release syndrome) and reversible to permanent (e.g. endocrinopathies).The mechanisms underpinning irAE pathology vary across different irAE complications and syndromes, reflecting the broad clinical phenotypes observed and the variability of different individual immune responses, and are poorly understood overall. Immune-related cardiovascular toxicities have emerged, and our understanding has evolved from focussing initially on rare but fatal ICI-related myocarditis with cardiogenic shock to more common complications including less severe ICI-related myocarditis, pericarditis, arrhythmias, including conduction system disease and heart block, non-inflammatory heart failure, takotsubo syndrome and coronary artery disease. In this scientific statement on the cardiovascular toxicities of immune therapies for cancer, we summarize the pathophysiology, epidemiology, diagnosis, and management of ICI, CAR-T, NK, and TIL therapies. We also highlight gaps in the literature and where future research should focus.

Germline predictors for bevacizumab induced hypertensive crisis in ECOG-ACRIN 5103 and BEATRICE.

BACKGROUND: Bevacizumab is a beneficial therapy in several advanced cancer types. Predictive biomarkers to better understand which patients are destined to benefit or experience toxicity are needed. Associations between bevacizumab induced hypertension and survival have been reported but with conflicting conclusions. METHODS: We performed post-hoc analyses to evaluate the association in 3124 patients from two phase III adjuvant breast cancer trials, E5103 and BEATRICE. Differences in invasive disease-free survival (IDFS) and overall survival (OS) between patients with hypertension and those without were compared. Hypertension was defined as systolic blood pressure (SBP) ≥ 160 mmHg (n = 346) and SBP ≥ 180 mmHg (hypertensive crisis) (n = 69). Genomic analyses were performed to evaluate germline genetic predictors for the hypertensive crisis. RESULTS: Hypertensive crisis was significantly associated with superior IDFS (p = 0.015) and OS (p = 0.042), but only IDFS (p = 0.029; HR = 0.28) remained significant after correction for prognostic factors. SBP ≥ 160 mmHg was not associated with either IDFS or OS. A common single-nucleotide polymorphism, rs6486785, was significantly associated with hypertensive crisis (p = 8.4 × 10-9; OR = 5.2). CONCLUSION: Bevacizumab-induced hypertensive crisis is associated with superior outcomes and rs6486785 predicted an increased risk of this key toxicity.

Functional and Radiologic Outcomes of Degenerative Versus Traumatic Full-Thickness Rotator Cuff Tears Involving the Supraspinatus Tendon.

BACKGROUND: Arthroscopic rotator cuff repair (ARCR) is among the most commonly performed orthopaedic procedures. Several factors-including age, sex, and tear severity-have been identified as predictors for outcome after repair. The influence of the tear etiology on functional and structural outcome remains controversial. PURPOSE: To investigate the influence of tear etiology (degenerative vs traumatic) on functional and structural outcomes in patients with supraspinatus tendon tears. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Patients undergoing ARCR from 19 centers were prospectively enrolled between June 2020 and November 2021. Full-thickness, nonmassive tears involving the supraspinatus tendon were included. Tears were classified as degenerative (chronic shoulder pain, no history of trauma) or traumatic (acute, traumatic onset, no previous shoulder pain). Range of motion, strength, the Subjective Shoulder Value, the Oxford Shoulder Score (OSS), and the Constant-Murley Score (CMS) were assessed before (baseline) and 6 and 12 months after ARCR. The Subjective Shoulder Value and the OSS were also determined at the 24-month follow-up. Repair integrity after 12 months was documented, as well as additional surgeries up to the 24-month follow-up. Tear groups were compared using mixed models adjusted for potential confounding effects. RESULTS: From a cohort of 973 consecutive patients, 421 patients (degenerative tear, n = 230; traumatic tear, n = 191) met the inclusion criteria. The traumatic tear group had lower mean baseline OSS and CMS scores but significantly greater score changes 12 months after ARCR (OSS, 18 [SD, 8]; CMS, 34 [SD,18] vs degenerative: OSS, 15 [SD, 8]; CMS, 22 [SD, 15]) (P < .001) and significantly higher 12-month overall scores (OSS, 44 [SD, 5]; CMS, 79 [SD, 9] vs degenerative: OSS, 42 [SD, 7]; CMS, 76 [SD, 12]) (P≤ .006). At the 24-month follow-up, neither the OSS (degenerative, 44 [SD, 6]; traumatic, 45 [SD, 6]; P = .346) nor the rates of repair failure (degenerative, 14 [6.1%]; traumatic 12 [6.3%]; P = .934) and additional surgeries (7 [3%]; 7 [3.7%]; P = .723) differed between groups. CONCLUSION: Patients with degenerative and traumatic full-thickness supraspinatus tendon tears who had ARCR show satisfactory short-term functional results. Although patients with traumatic tears have lower baseline functional scores, they rehabilitate over time and show comparable clinical results 1 year after ARCR. Similarly, degenerative and traumatic rotator cuff tears show comparable structural outcomes, which suggests that degenerated tendons retain healing potential.

The effect of intravenous tranexamic acid on visual clarity in arthroscopic shoulder surgery compared to epinephrine and a placebo: a double-blinded, randomized controlled trial.

BACKGROUND: The addition of epinephrine in irrigation fluid and the intravenous or local administration of tranexamic acid have independently been reported to decrease bleeding, thereby improving surgeons' visualization during arthroscopic shoulder procedures. No study has compared the effect of intravenous tranexamic acid, epinephrine in the irrigation fluid, or the combination of both tranexamic acid and epinephrine on visual clarity during shoulder arthroscopy with a placebo group. We hypothesized that intravenous tranexamic acid is more effective than epinephrine mixed in the irrigation fluid in improving visualization during shoulder arthroscopy, with no additive effect when both are used. METHODS: Patients aged ≥18 years undergoing shoulder arthroscopy were randomized into one of 4 study arms: (1) saline irrigation fluid (placebo); (2) epinephrine (0.33 mL of 1:1000 per liter) mixed in irrigation fluid (EPI); (3) 1 g intravenous tranexamic acid (TXA); and (4) epinephrine and tranexamic acid combined (TXA + EPI). Visualization was rated intraoperatively on a scale from 0, indicating poor clarity, to 3, indicating excellent clarity, every 15 minutes and overall. The primary outcome measure was the overall rating of visualization. A stepwise linear regression was performed using visualization as the dependent variable and independent variables including presence or absence of epinephrine and tranexamic acid, surgery duration, complexity, mean arterial pressure, increase in pump pressure, and volume of irrigation fluid. RESULTS: One hundred twenty-eight patients (mean age 56 years) were randomized. Mean visual clarity for the placebo, TXA, EPI, and TXA + EPI groups were 2.0 (±0.6), 2.0 (±0.6), 2.6 (±0.5), and 2.7 (±0.5), respectively (P < .001). The presence or absence of epinephrine was the most significant predictor of visual clarity (P < .001). Tranexamic acid presence or absence had no effect. No adverse events were recorded in any of the groups. CONCLUSION: Intravenous tranexamic acid is not an effective alternative to epinephrine in irrigation fluid to improve visualization during routine arthroscopic shoulder surgeries, and there is no additive effect when both are used.

Acute surgical treatment of entrapped avulsion fractures of the inferior angle of the scapula in adults: Two case reports.

Inferior angle of scapula fractures are rare, and can lead to pain and impaired shoulder function. This report details the cases of two adult patients with inferior angle of scapula fractures who underwent acute surgical reduction and suture repair. In both patients, the avulsed fragment was dislocated and entrapped in the scapulothoracic joint resulting in noticeable crepitations and disturbed scapulothoracic rhythm during active range of motion. After surgery, both patients achieved significant improvements in shoulder function, enabling them to resume their daily activities without limitations. Fracture healing was uneventful in both cases. While the optimal treatment strategy for acute inferior angle of scapula fractures is still debated, early surgical intervention with suture fixation may offer favorable outcomes for patients with displaced fractures entrapped in the scapulothoracic joint, presenting with crepitus and disrupted scapulothoracic rhythm. Further research is needed to establish evidence-based guidelines for managing these rare fractures.

European Society of Cardiology Core Curriculum for cardio-oncology.

Cardio-oncology is a rapidly growing field of cardiovascular (CV) medicine that has resulted from the continuously increasing clinical demand for specialized CV evaluation, prevention and management of patients suffering or surviving from malignant diseases. Dealing with CV disease in patients with cancer requires special knowledge beyond that included in the general core curriculum for cardiology. Therefore, the European Society of Cardiology (ESC) has developed a special core curriculum for cardio-oncology, a consensus document that defines the level of experience and knowledge required for cardiologists in this particular field. It is structured into 8 chapters, including (i) principles of cancer biology and therapy; (ii) forms and definitions of cancer therapy-related cardiovascular toxicity (CTR-CVT); (iii) risk stratification, prevention and monitoring protocols for CTR-CVT; (iv) diagnosis and management of CV disease in patients with cancer; (v) long-term survivorship programmes and cardio-oncology rehabilitation; (vi) multidisciplinary team management of special populations; (vii) organization of cardio-oncology services; (viii) research in cardio-oncology. The core curriculum aims at promoting standardization and harmonization of training and evaluation in cardio-oncology, while it further provides the ground for an ESC certification programme designed to recognize the competencies of certified specialists.

Supervised exercise training in patients with cancer during anthracycline-based chemotherapy to mitigate cardiotoxicity: a randomized-controlled-trial.

Background: Exercise training (ET) has been shown to mitigate cardiotoxicity of anthracycline-based chemotherapies (AC) in animal models. Data from randomized controlled trials in patients with cancer are sparse. Methods: Patients with breast cancer or lymphoma receiving AC were recruited from four cancer centres and randomly assigned to 3 months supervised ET. Primary outcome was change in left ventricular global longitudinal strain (GLS) from baseline (before AC) to post AC (AC-end) compared between the EXduringAC group, who participated in an exercise intervention during AC including the provision of an activity tracker, and the control group EXpostAC, who received an activity tracker only. Secondary outcome parameters were changes in high sensitivity Troponin T (hsTnT), NT-pro-brain natriuretic peptide (NT-proBNP), peak oxygen consumption (peak VO2) and objectively measured physical activity (PA) during this same time-period. All assessments were repeated at a 12-week follow-up from AC-end, when also the EXpostAC group had completed the ET, that started after AC. In exploratory analyses, robust linear models were performed to assess the association of PA with changes in echocardiographic parameters and biomarkers of LV function. Results: Fifty-seven patients (median age 47 years; 95% women) were randomized to EXduringAC (n = 28) and EXpostAC (n = 29) group. At AC-end, GLS deteriorated in both study groups (albeit insignificantly) with 7.4% and 1.0% in EXduringAC (n = 18) and EXpostAC (n = 18), respectively, and hsTnT and NT-proBNP significantly increased in both groups, without difference between groups for any parameter. Change in peak VO2 (-1.0 and -1.1 ml/kg/min) at AC-end was also similar between groups as was duration of moderate-to-vigorous PA (MVPA) with a median of 33 [26, 47] min/day and 32 [21, 59] min/day in the EXduringAC and EXpostAC group, respectively. In the robust linear model including the pooled patient population, MVPA was significantly associated with a more negative GLS and lesser increase in hsTnT at AC-end. Conclusion: In this small scale RCT, supervised ET during AC was not superior to wearing a PA tracker to mitigate cardiotoxicity. The dose-response relationship between PA and cardioprotective effects during AC found in our and previous data supports the notion that PA should be recommended to patients undergoing AC. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03850171.

Incidental detection of malignancy during preprocedural workup for transcatheter aortic valve implantation: A longitudinal cohort study.

The aim of this retrospective analysis was to investigate the prevalence and prognostic importance of incidental malignancy detected during pre-TAVI computed tomography. Among 579 patients, CT-work-up for TAVI exposed previously undetected malignancy in 4.5% of patients. TAVI patients with a new malignancy had a 2.9-fold increased risk of death at 1 year, and a 16 month shorter mean survival time compared to patients with no malignancy.

Open anatomical glenoid reconstruction with an iliac crest bone autograft effectively resolves off-track Hill-Sachs lesions to on-track lesions.

INTRODUCTION: The purpose of this study was to determine if "off-track" Hill-Sachs lesions in patients with dynamic anteroinferior instability were transformed into "on-track" lesions using iliac bone autografts with screw fixation. The secondary purpose was to observe if postoperative bony remodeling would occur over time, resulting in recurrent "off-track" Hill-Sachs lesions with corresponding instability. MATERIALS AND METHODS: We retrospectively reviewed clinical and CT records of 8 patients with an "off-track" Hill-Sachs lesion who underwent open anatomical glenoid reconstruction with an iliac crest bone autograft. Hill-Sachs lesions, glenoid track widths, and glenoid surface areas were measured on a preoperative and two postoperative (6 weeks, ≥ 2 years) 3D-CT models to determine graft resorption over time. All patients were available for postoperative clinical and CT final follow-up 3 years (2-4 years) postoperatively. RESULTS: In all patients, the Hill-Sachs lesions were "on-track" 6 weeks postoperatively and remained "on-track" at final-follow-up. Compared to preoperative values, the glenoid track width and glenoid surface area both were higher 6 weeks postoperatively (p < 0.001 and p = 0.023, respectively) and at final follow-up (p < 0.001 and p = 0.023, respectively). Whereas the glenoid track width between 6 weeks and final follow-up showed no decrease (p = 0.234), glenoid surface area tended to decrease (p = 0.055). The median SSV was 93 points (85-95 points), the Rowe score 90 points (80-100 points) and the WOSI 1980 points (1783-2067 points) at final follow-up. No recurrent dislocations or subluxations were observed. CONCLUSIONS: An open anatomical glenoid reconstruction with an iliac crest bone autograft technique using screw fixation effectively transformed "off-track" Hill-Sachs lesions to "on-track" lesions, resulting in good short-term clinical outcomes. Whereas glenoid surface area tended to be reduced by bony remodeling processes over time, the glenoid track width did not decrease at final follow-up and consequently no recurrence of "off-track" lesions occurred. LEVEL OF EVIDENCE: Case series; Level of evidence, IV.

Time-Dependent Effect of Anthracycline-Based Chemotherapy on Central Arterial Stiffness: A Systematic Review and Meta-Analysis.

Background and Aims: Anthracycline-based chemotherapy (ANTH-BC) has been proposed to increase arterial stiffness, however, the time-dependency of these effects remain unclear. This systematic review and meta-analysis aimed to investigate the time-dependent effect of ANTH-BC on markers of central aortic stiffness, namely aortic distensibility (AD) and pulse-wave-velocity (PWV) in cancer patients. Methods: An extensive literature search without language restrictions was performed to identify all studies presenting longitudinal data on the effect of ANTH-BC on either AD and/or central PWV in cancer patients of all ages. An inverse-variance weighted random-effect model was performed with differences from before to after chemotherapy, as well as for short vs. mid-term effects. Results: Of 2,130 articles identified, 9 observational studies with a total of 535 patients (mean age 52 ± 11; 73% women) were included, of which four studies measured AD and seven PWV. Short-term (2-4 months), there was a clinically meaningful increase in arterial stiffness, namely an increase in PWV of 2.05 m/s (95% CI 0.68-3.43) and a decrease in AD (albeit non-significant) of -1.49 mmHg-1 (-3.25 to 0.27) but a smaller effect was observed mid-term (6-12 months) for PWV of 0.88 m/s (-0.25 to 2.02) and AD of -0.37 mmHg-1 (-1.13 to 0.39). There was considerable heterogeneity among the studies. Conclusions: Results from this analysis suggest that in the short-term, ANTH-BC increases arterial stiffness, but that these changes may partly be reversible after therapy termination. Future studies need to elucidate the long-term consequences of ANTH-BC on arterial stiffness, by performing repeated follow-up measurements after ANTH-BC termination. Systematic Review Registration: [www.crd.york.ac.uk/prospero/], identifier [CRD42019141837].

Influence of atrial fibrillation on efficacy and safety of omecamtiv mecarbil in heart failure: the GALACTIC-HF trial.

AIMS: In GALACTIC-HF, the cardiac myosin activator omecamtiv mecarbil compared with placebo reduced the risk of heart failure events or cardiovascular death in patients with heart failure with reduced ejection fraction. We explored the influence of atrial fibrillation or flutter (AFF) on the effectiveness of omecamtiv mecarbil. METHODS AND RESULTS: GALACTIC-HF enrolled patients with New York Heart Association (NYHA) Class II-IV heart failure, left ventricular ejection fraction ≤35%, and elevated natriuretic peptides. We assessed whether the presence or absence of AFF, a pre-specified subgroup, modified the treatment effect for the primary and secondary outcomes, and additionally explored effect modification in patients who were or were not receiving digoxin. Patients with AFF (n = 2245, 27%) were older, more likely to be randomized as an inpatient, less likely to have a history of ischaemic aetiology or myocardial infarction, had a worse NYHA class, worse quality of life, lower estimated glomerular filtration rate, and higher N-terminal pro-B-type natriuretic peptide. The treatment effect of omecamtiv mecarbil was modified by baseline AFF (interaction P = 0.012), with patients without AFF at baseline deriving greater benefit. The worsening of the treatment effect by baseline AFF was significantly more pronounced in digoxin users than in non-users (interaction P = 0.007); there was minimal evidence of effect modification in those patients not using digoxin (P = 0.47) or in digoxin users not in AFF. CONCLUSION: Patients in AFF at baseline were less likely to benefit from omecamtiv mecarbil than patients without AFF, although the attenuation of the treatment effect was disproportionally concentrated in patients with AFF who were also receiving digoxin.Clinical Trial Registration: NCT02929329.

Accuracy of free-hand humeral head resection planned on 3D-CT models in shoulder arthroplasty: an in vitro analysis.

INTRODUCTION: Three-dimensional planning of humeral head osteotomy in shoulder arthroplasty (SA) is understudied. This study evaluated whether a standard osteotomy technique along the anterosuperior anatomic neck (ASOT) could be surgically reproduced as pre-operatively planned on 3D-CT models. MATERIAL AND METHODS: Pre-operative planning in 12 cadaver shoulders was performed on a 3D-CT model of the humerus to calculate the planned osteotomy plane (planned OP). The osteotomy was then performed using a free-hand technique, and a post-operative CT scan was obtained for analysis (performed OP). Planes were compared with regards to inclination, retroversion, and resected humeral head thickness so the accuracy could be quantified. RESULTS: The absolute errors between the performed and planned OP were 2° (0-10°), 5° (0-14°), and 4 mm (1-7 mm) for inclination, retroversion, and resected head thickness, respectively. Deviation < 10° for inclination and retroversion and < 5 mm for resected humeral head thickness between planned and performed OP was achieved in 92%, 83%, 58% of cases, respectively. No differences were found for inclination (p = 0.289), whereas retroversion and resected head thickness were smaller than planned (p ≤ 0.027). CONCLUSIONS: Pre-operative planning of the ASOT using a 3D-CT model is accurate within a threshold of 10° when using a free-hand technique in 92% of cases for inclination. Retroversion and resected head thickness differed from the pre-operative plan, thereby limiting the unrestricted use of humeral head osteotomy planning from 3D-CT models in SA. These findings are a reference for further studies to develop and quantify the accuracy of pre-operative planning software including cutting guides for SA using 3D-CT models. LEVEL OF EVIDENCE: Basic science article.

Management of transthyretin amyloidosis.

Transthyretin amyloidosis (ATTR amyloidosis) is a disease caused by deposition of transthyretin fibrils in organs and tissues, which causes their dysfunction. The clinical heterogeneity of ATTR amyloidosis and the variable presentation of symptoms at early disease stages, historically meant treatment delays. Diagnostic tools and therapy options of ATTR amyloidosis have markedly improved in recent years. The first Swiss Amyloidosis Network (SAN) meeting (Zurich, Switzerland, January 2020) aimed to define a consensus statement regarding the diagnostic work-up and treatment for systemic amyloidosis, tailored to the Swiss healthcare system. A consortium of 45 clinicians and researchers from all Swiss regions and universities was selected by the SAN committee to represent all sub-specialty groups involved in care of patients with amyloidosis. A steering committee conducted the literature search and analysis, wrote the critical synthesis and elaborated a list of statements that were evaluated by all the participants. These recommendations will improve outcomes and quality of life for patients with ATTR amyloidosis. A global review of these guidelines is planned every 3 years with a formal meeting of all the involved experts.

Swiss-wide multicentre evaluation and prediction of core outcomes in arthroscopic rotator cuff repair: protocol for the ARCR_Pred cohort study.

INTRODUCTION: In the field of arthroscopic rotator cuff repair (ARCR), reporting standards of published studies differ dramatically, notably concerning adverse events (AEs). In addition, prognostic studies are overall methodologically poor, based on small data sets and explore only limited numbers of influencing factors. We aim to develop prognostic models for individual ARCR patients, primarily for the patient-reported assessment of shoulder function (Oxford Shoulder Score (OSS)) and the occurrence of shoulder stiffness 6 months after surgery. We also aim to evaluate the use of a consensus core event set (CES) for AEs and validate a severity classification for these events, considering the patient's perspective. METHODS AND ANALYSIS: A cohort of 970 primary ARCR patients will be prospectively documented from several Swiss and German orthopaedic clinics up to 24 months postoperatively. Patient clinical examinations at 6 and 12 months will include shoulder range of motion and strength (Constant Score). Tendon repair integrity status will be assessed by ultrasound at 12 months. Patient-reported questionnaires at 6, 12 and 24 months will determine functional scores (subjective shoulder value, OSS), anxiety and depression scores, working status, sports activities, and quality of life (European Quality of Life 5 Dimensions 5 Level questionnaire). AEs will be documented according to a CES. Prognostic models will be developed using an internationally supported regression methodology. Multiple prognostic factors, including patient baseline demographics, psychological, socioeconomic and clinical factors, rotator cuff integrity, concomitant local findings, and (post)operative management factors, will be investigated. ETHICS AND DISSEMINATION: This project contributes to the development of personalised risk predictions for supporting the surgical decision process in ARCR. The consensus CES may become an international reference for the reporting of complications in clinical studies and registries. Ethical approval was obtained on 1 April 2020 from the lead ethics committee (EKNZ, Basel, Switzerland; ID: 2019-02076). All participants will provide informed written consent before enrolment in the study. TRIAL REGISTRATION NUMBER: NCT04321005. PROTOCOL VERSION: Version 2 (13 December 2019).

Editorial Commentary: Is Your Critical Shoulder Angle Accurate? Only If You Can Verify That You Have the Correct Images.

The critical shoulder angle (CSA) has been the focus of significant research related to the etiology and prognosis of rotator cuff tears in recent years, but the accuracy of CSA measurements on plain anteroposterior (Grashey) radiographs has been questioned. Research to better understand what qualifies as a "tolerable" radiograph for reliable measurement of the CSA can inform best practices for obtaining plain radiographs. Optimal measurements rely on optimal images, and knowing how much room for error there is regarding malrotation provides surgeons with unbiased criteria to rule out inadequate images.

Anticoagulation in patients with atrial fibrillation and active cancer: an international survey on patient management.

BACKGROUND: In patients with active cancer and atrial fibrillation (AF) anticoagulation, thrombotic and bleeding risk still entail uncertainty. AIM: We explored the results of an international survey examining the knowledge and behaviours of a large group of physicians. METHODS AND RESULTS: A web-based survey was completed by 960 physicians (82.4% cardiologists, 75.5% from Europe). Among the currently available anticoagulants for stroke prevention in patients with active cancer, direct oral anticoagulants (DOACs) were preferred by 62.6%, with lower values for low molecular weight heparin (LMWH) (24.1%) and for warfarin (only 7.3%). About 46% of respondents considered that DOACs should be used in all types of cancers except in non-operable gastrointestinal cancers. The lack of controlled studies on bleeding risk (33.5% of respondents) and the risk of drug interactions (31.5%) were perceived as problematic issues associated with use of anticoagulants in cancer. The decision on anticoagulation involved a cardiologist in 27.8% of cases, a cardiologist and an oncologist in 41.1%, and a team approach in 21.6%. The patient also was involved in decision-making, according to ∼60% of the respondents. For risk stratification, use of CHA2DS2-VASc and HAS-BLED scores was considered appropriate, although not specifically validated in cancer patients, by 66.7% and 56.4%, respectively. CONCLUSION: This survey highlights that management of anticoagulation in patients with AF and active cancer is challenging, with substantial heterogeneity in therapeutic choices. Direct oral anticoagulants seems having an emerging role but still the use of LMWH remains substantial, despite the absence of long-term data on thromboprophylaxis in AF.

Risk of bleeding complications and atrial fibrillation associated with ibrutinib treatment: A systematic review and meta-analysis.

The use of ibrutinib is hampered by major bleeding events and atrial fibrillation. Speculating whether randomized controlled trials might underestimate the risk of adverse events in clinical practice, we conducted a systematic review and meta-analysis studying patients treated in any setting and indication. We systematically searched the literature using MEDLINE and EMBASE databases for case series, cohort studies, or randomized controlled trials and retrieved all data in parallel. Proportions of patients with adverse events were pooled in relevant subgroups using the binominal distribution and Freeman-Tukey double arcsine transformation. Among 2'537 records screened, 85 were finally included, comprising 7'317 patients. Methodological quality according to the Newcastle-Ottawa Scale was rated as moderate to poor with regard to bleeding events and atrial fibrillation; 106 studies were excluded because of missing data at all. Reported events varied substantially between 0 % and 78 % (any bleedings), 0 % and 25 % (major bleedings), and 0 % and 38 % (new-onset atrial fibrillation). Pooled estimates were 28 % (95 % confidence interval 22 %, 34 %), 3 % (2 %, 4 %), and 8 % respectively (7 %, 10 %). The risk of events was higher in studies with an older population, high ibrutinib dosage, thrombocytopenia, antithrombotic treatment, and retrospective studies. In conclusions, reporting of bleeding events and atrial fibrillation varied substantially among studies. These observations, in combination with the estimates obtained, suggest a relevant risk in clinical practice.