Embolic strokes of undetermined source: a clinical consensus statement of the ESC Council on Stroke, the European Association of Cardiovascular Imaging and the European Heart Rhythm Association of the ESC.

One in six ischaemic stroke patients has an embolic stroke of undetermined source (ESUS), defined as a stroke with unclear aetiology despite recommended diagnostic evaluation. The overall cardiovascular risk of ESUS is high and it is important to optimize strategies to prevent recurrent stroke and other cardiovascular events. The aim of clinicians when confronted with a patient not only with ESUS but also with any other medical condition of unclear aetiology is to identify the actual cause amongst a list of potential differential diagnoses, in order to optimize secondary prevention. However, specifically in ESUS, this may be challenging as multiple potential thromboembolic sources frequently coexist. Also, it can be delusively reassuring because despite the implementation of specific treatments for the individual pathology presumed to be the actual thromboembolic source, patients can still be vulnerable to stroke and other cardiovascular events caused by other pathologies already identified during the index diagnostic evaluation but whose thromboembolic potential was underestimated. Therefore, rather than trying to presume which particular mechanism is the actual embolic source in an ESUS patient, it is important to assess the overall thromboembolic risk of the patient through synthesis of the individual risks linked to all pathologies present, regardless if presumed causally associated or not. In this paper, a multi-disciplinary panel of clinicians/researchers from various backgrounds of expertise and specialties (cardiology, internal medicine, neurology, radiology and vascular surgery) proposes a comprehensive multi-dimensional assessment of the overall thromboembolic risk in ESUS patients through the composition of individual risks associated with all prevalent pathologies.

Long-term cardiac effects of modern treatment for Hodgkin's lymphoma.

BACKGROUND: Hodgkin's lymphoma (HL) is a hematological malignancy that affects both children and young adults. Traditional treatment is associated with a life-time prevalence of cardiac disease exceeding 50%. In the late 1990s protocols were modified to reduce cancer therapy-related adverse cardiac effects. This study aimed to assess the long-term impact of advances in treatment protocols on the cardiac health of HL survivors (HLS). METHODS: HLS (n = 246) treated between 1997 and 2007 with anthracycline-based chemotherapy in three centers in Norway were included. Of these, 132 (53%) had also received mediastinal radiotherapy. HLS were compared to controls (n = 58) recruited from the general population and matched for sex, age, smoking status, and heredity for coronary artery disease. All subjects underwent echocardiography, clinical assessment, and blood sampling. RESULTS: The HLS were 46 ± 9 years old and had been treated 17 ± 3 years before inclusion in the study. There was no significant difference between HLS and controls in ejection fraction (EF) (58%±5 vs. 59%±4, p = 0.08) or prevalence of heart failure. HLS treated with both anthracyclines and mediastinal radiotherapy (AC + MRT) had slightly worse left ventricular global longitudinal strain than controls (-19.3 ± 2.5% vs. -20.8 ± 2.0%, p < 0.001), but those treated with only anthracyclines did not. HLS treated with AC + MRT had a higher prevalence of valve disease than those treated only with anthracyclines (12% vs. 4%, p < 0.05). CONCLUSIONS: HLS treated with anthracyclines after the late 1990s have similar cardiac function and morphology as age-matched controls, apart from higher rates of valvular disease in those who also underwent mediastinal radiotherapy.

Elevated interleukin 8 and matrix metalloproteinase 9 levels are associated with myocardial pathology in users of Anabolic-Androgenic Steroids.

AIM: In the current paper, we aim to explore the effect of both current and former long-term anabolic-androgenic steroid (AAS) use on regulation of systemic inflammatory markers and mediators of extracellular matrix (ECM) remodeling and their association with hormones and echocardiographic myocardial pathology in weightlifters. METHODS: In a cross-sectional study, 93 weightlifting AAS-users, of which 62 were current and 31 were past users, with at least one-year cumulative AAS-use (mean 11±7 accumulated years of AAS-use), were compared to 54 non-using weightlifting controls (WLC) using clinical interview, blood pressure measurements, and echocardiography. RESULTS: Serum levels of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF), interferon (IFN)γ, growth differentiation factor (GDF)-15 and matrix metalloproteinase (MMP-9), sex hormones and lipids were analyzed. Serum levels of IL-8, GDF-15 and MMP-9 were significantly increased in current AAS users compared to former users and WLC. MMP-9, but not IL-8, correlated consistently with sex-hormone levels, and sex-hormone levels correlated consistently with mean wall thickness, in current users. Moreover, HDL cholesterol was significantly lower in current versus former AAS users, in significantly inversely correlated with MMP-9 in current users. Further, in current users, MMP-9 and IL-8 correlated with markers of myocardial strain, and MMP9 also with indices of cardiac mass, which was not seen in former users. Mediation analyses suggested that MMP-9 could partly explain hormone-induced alterations in markers of myocardial damage in current users. CONCLUSION: In conclusion, long-term AAS is associated with increased levels of markers of inflammation and extracellular matrix remodeling, which seems to have a hormone-dependent (MMP-9) and hormone-independent (IL-8) association with markers of myocardial dysfunction.

Long-term use of anabolic-androgenic steroids (AAS) can increase inflammation and mediators of extracellular matrix (ECM) remodeling which potentially could be involved in myocardial pathology seen in these individuals. AAS use increased levels of inflammatory marker IL-8 and marker of ECM remodeling MMP-9.IL-8 and MMP-9 were both associated with myocardial pathology in current, but not former users, suggesting that these markers are association with risk of myocardial damage during AAS use.

Current clinical use of speckle-tracking strain imaging: insights from a worldwide survey from the European Association of Cardiovascular Imaging (EACVI).

AIMS: Speckle-tracking echocardiography (STE) strain imaging has been a major advancement in myocardial function quantification. We aimed to explore current worldwide clinical application of STE. METHODS AND RESULTS: Access, feasibility, access, and clinical implementation of STE were investigated with a worldwide open-access online survey of the European Association of Cardiovascular Imaging. Participants (429 respondents and 77 countries) from tertiary centres (46%), private clinics, or public hospitals (54%) using different vendors for data acquisition and analysis were represented. Despite almost universal access (98%) to STE, only 39% of the participants performed and reported STE results frequently (>50%). Incomplete training and time constraints were the main reasons for not using STE more regularly. STE was mainly used to assess the LV (99%) and less frequently the right ventricular (57%) and the left atrial (46%) function. Cardiotoxicity (88%) and cardiac amyloidosis (87%) were the most frequent reasons for the clinical use of LV STE. Left atrial STE was used most frequently for the diagnosis of diastolic dysfunction and right ventricular STE for the assessment of right ventricle (RV) function in pulmonary hypertension (51%). Frequency of STE use, adherence to optimal techniques, and clinical appropriateness of STE differed according to training experience and across vendors. Key suggestions outlined by respondents to increase the clinical use of STE included improved reproducibility (48%) and standardization of strain values across vendors (42%). CONCLUSION: Although STE is now readily available, it is underutilized in the majority of centres. Structured training, improved reproducibility, and inter-vendor standardization may increase its uptake.

Highly malignant disease in childhood-onset arrhythmogenic right ventricular cardiomyopathy.

AIMS: This study aimed to explore the incidence of severe cardiac events in paediatric arrhythmogenic right ventricular cardiomyopathy (ARVC) patients and ARVC penetrance in paediatric relatives. Furthermore, the phenotype in childhood-onset ARVC was described. METHODS: Consecutive ARVC paediatric patients and genotype positive relatives ≤18 years of age were followed with electrocardiographic, structural, and arrhythmic characteristics according to the 2010 revised Task Force Criteria. Penetrance of ARVC disease was defined as fulfilling definite ARVC criteria and severe cardiac events were defined as cardiac death, heart transplantation (HTx) or severe ventricular arrhythmias. Childhood-onset disease was defined as meeting definite ARVC criteria ≤12 years of age. RESULTS: Among 62 individuals [age 9.8 (5.0-14.0) years, 11 probands], 20 (32%) fulfilled definite ARVC diagnosis, of which 8 (40%) had childhood-onset disease. The incidence of severe cardiac events was 23% (n = 14) by last follow-up and half of them occurred in patients ≤12 years of age. Among the eight patients with childhood-onset disease, five had biventricular involvement needing HTx and three had severe arrhythmic events. Among the 51 relatives, 6% (n = 3) met definite ARVC criteria at time of genetic diagnosis, increasing to 18% (n = 9) at end of follow-up. CONCLUSIONS: In a paediatric ARVC cohort, there was a high incidence of severe cardiac events and half of them occurred in children ≤12 years of age. The ARVC penetrance in genotype positive paediatric relatives was 18%. These findings of a high-malignant phenotype in childhood-onset ARVC indicate a need for ARVC family screening at younger age than currently recommended.

Intravenous iron supplement for iron deficiency in patients with severe aortic stenosis scheduled for transcatheter aortic valve implantation: results of the IIISAS randomised trial.

AIMS: The aim of this trial was to evaluate whether intravenous iron could provide benefit beyond transcatheter aortic valve implantation (TAVI) in iron-deficient patients with severe aortic stenosis. METHODS AND RESULTS: In this randomised, placebo-controlled, double-blind, single-centre trial, we enrolled patients with severe aortic stenosis and iron deficiency (defined as ferritin <100 µg/L, or 100-299 µg/L with a transferrin saturation <20%) who were evaluated for TAVI. Patients were randomly assigned (1:1) to receive intravenous ferric derisomaltose or placebo ∼3 months before TAVI. The primary endpoint was the between-group, baseline-adjusted 6-min walk distance measured 3 months after TAVI. Secondary outcomes included quality of life, iron stores, hand grip strength, New York Heart Association (NYHA) class, and safety. Between January 2020 and September 2021, we randomised 74 patients to ferric derisomaltose and 75 patients to placebo. The modified intention-to-treat population comprised the 104 patients who completed the 6-min walk test at baseline and 3 months after successful TAVI. Iron stores were restored in 76% of the patients allocated to iron and 13% of the patients allocated to placebo (p < 0.001). There was no difference in the baseline-adjusted 6-min walk distance between the two treatment arms (p = 0.82). The number of serious adverse events, quality of life, hand grip strength, and NYHA class did not differ between the treatment arms. CONCLUSION: Treatment with intravenous iron did not provide clinical benefit beyond TAVI in iron-deficient patients with severe aortic stenosis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT04206228.

Novel regional longitudinal strain by speckle tracking to detect significant coronary artery disease in patients admitted to the emergency department for chest pain suggestive of acute coronary syndrome.

BACKGROUND: Global longitudinal strain has shown variable results in detecting ischemia in patients admitted to the emergency department with chest pain, but without other clear evidence of coronary artery disease (CAD). Our aim was to investigate whether assessment of regional longitudinal myocardial function could assist in detecting significant CAD in these patients. METHODS: Clinical evaluation, electrocardiogram, echocardiogram and troponin T were evaluated in 126 patients admitted with chest pain. A subsequent invasive coronary angiography divided patients into two groups: significant CAD (CAD+) or non-significant CAD (CAD-). Global and regional myocardial function were evaluated by speckle tracking echocardiography. Regional longitudinal strain was defined as the highest longitudinal strain values in four adjacent left ventricular segments and termed 4AS. RESULTS: CAD+ was found in 37 patients (29%) of which 51% had elevated troponin. Mean 4AS was - 13.1% (± 3.5) in the CAD+ and - 15.2% (± 2.7) (p = 0.002) in the CAD- group. Predictors for CAD+ were age [OR 1.06 (1.01-1.11, p = 0.026)], smoking [OR 3.39 (1.21-9.51, p = 0.020)], troponin [OR 3.32 (1.28-8.60, p = 0.014)) and 4AS (OR 1.24 (1.05-1.46, p = 0.010)]. A cutoff for 4AS of > - 15% showed the best diagnostic performance with event-reclassification of 0.41 (p < 0.001), non-event-reclassification of - 0.34 (p < 0.001) and net reclassification improvement 0.07 (p = 0.60). CONCLUSION: Decreased myocardial function in four adjacent LV segments assessed by strain has the potential to detect significant CAD in patients admitted with chest pain and negative/slightly elevated initial troponin. TRIAL REGISTRATION: Current Research information system in Norway (CRISTIN). Id: 555249.

Intravenous ferric derisomaltose in iron-deficient patients undergoing transcatheter aortic valve implantation due to severe aortic stenosis: study protocol of the randomised controlled IIISAS trial.

INTRODUCTION: Iron deficiency is a prevalent comorbidity in patients with severe aortic stenosis and may be associated with procedural and clinical outcomes after transcatheter aortic valve implantation (TAVI). In the Intravenous Iron Supplement for Iron Deficiency in Patients with Severe Aortic Stenosis (IIISAS) trial, we aim to examine whether a single administration of ferric derisomaltose can improve physical capacity after TAVI. METHODS AND ANALYSIS: This randomised, double-blind, placebo-controlled trial aims to enrol 150 patients with iron deficiency who are scheduled for TAVI due to severe aortic stenosis. The study drug and matching placebo are administered approximately 3 months prior to TAVI, and the patients are followed for 3 months after TAVI. Inclusion criteria are iron deficiency, defined as serum ferritin<100 µg/L or ferritin between 100 and 300 µg/L in combination with a transferrin saturation<20% and written informed consent. Exclusion criteria include haemoglobin<10 g/dL, red blood cell disorders, end-stage kidney failure, intolerance to ferric derisomaltose, and ongoing infections. The primary endpoint is the baseline-adjusted distance walked on a 6 min walk test (6MWT) 3 months after TAVI. Secondary end points include quality of life, New York Heart Association functional class (NYHA functional class), and skeletal muscle strength. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Regional Committee for Medical and Health Research of South-Eastern Norway and The Norwegian Medicines Agency. Enrolment has begun, and results are expected in 2022. The results of the IIISAS trial will be disseminated by presentations at international and national conferences and by publications in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04206228.

Genetic Variant Score and Arrhythmogenic Right Ventricular Cardiomyopathy Phenotype in Plakophilin-2 Mutation Carriers.

INTRODUCTION: Whether detailed genetic information contributes to risk stratification of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) remains uncertain. Pathogenic genetic variants in some genes seem to carry a higher risk for arrhythmia and earlier disease onset than others, but comparisons between variants in the same gene have not been done. Combined Annotation Dependent Depletion (CADD) score is a bioinformatics tool that measures the pathogenicity of each genetic variant. We hypothesized that a higher CADD score is associated with arrhythmic events and earlier age at ARVC manifestations in individuals carrying pathogenic or likely pathogenic genetic variants in plakophilin-2 (PKP2). METHODS: CADD scores were calculated using the data from pooled Scandinavian and North American ARVC cohorts, and their association with cardiac events defined as ventricular tachycardia/ventricular fibrillation (VT/VF) or syncope and age at definite ARVC diagnosis were assessed. RESULTS: In total, 33 unique genetic variants were reported in 179 patients (90 males, 71 probands, 96 with definite ARVC diagnosis at a median age of 35 years). Cardiac events were reported in 76 individuals (43%), of whom 53 had sustained VT/VF (35%). The CADD score was neither associated with age at cardiac events (HR 1.002, 95% CI: 0.953-1.054, p = 0.933) nor with age at definite ARVC diagnosis (HR 0.992, 95% CI: 0.947-1.039, p = 0.731). CONCLUSION: No correlation was found between CADD scores and clinical manifestations of ARVC, indicating that the score has no additional risk stratification value among carriers of pathogenic or likely pathogenic PKP2 genetic variants.

Ultrasound contrast agent hypersensitivity in patients allergic to polyethylene glycol: position statement by the European Association of Cardiovascular Imaging.

The Food and Drug Administration alert enhances our understanding of the mechanism of severe reactions to ultrasound-enhancing agents (UEAs). The known incidence of these reactions remains low and unchanged (1 in 10 000 administrations). Because the risk-to-benefit ratio for ultrasound contrast agents (UCAs) remains extremely low, we do not advise any changes to laboratory policy regarding indications for their use. The use of these agents should continue in situations where they have been shown to be impactful. Lipid-based UCAs (SonoVue and Luminity) are contraindicated in patients who have a history of prior hypersensitivity to these UEAs, to polyethylene glycol (PEG) (macrogol), or to PEG-containing products, such as certain bowel preps for colonoscopy or laxatives.

Sex differences in disease progression and arrhythmic risk in patients with arrhythmogenic cardiomyopathy.

AIMS: We aimed to assess sex-specific phenotypes and disease progression, and their relation to exercise, in arrhythmogenic cardiomyopathy (AC) patients. METHODS AND RESULTS: In this longitudinal cohort study, we included consecutive patients with AC from a referral centre. We performed echocardiography at baseline and repeatedly during follow-up. Patients' exercise dose at inclusion was expressed as metabolic equivalents of task (MET)-h/week. Ventricular arrhythmia (VA) was defined as aborted cardiac arrest, sustained ventricular tachycardia, or appropriate therapy by implantable cardioverter-defibrillator. We included 190 AC patients (45% female, 51% probands, age 41 ± 17 years). Ventricular arrhythmia had occurred at inclusion or occurred during follow-up in 85 patients (33% of females vs. 55% of males, P = 0.002). Exercise doses were higher in males compared with females [25 (interquartile range, IQR 14-51) vs. 12 (IQR 7-22) MET-h/week, P < 0.001]. Male sex was a marker of proband status [odds ratio (OR) 2.6, 95% confidence interval (CI) 1.4-5.0, P = 0.003] and a marker of VA (OR 2.6, 95% CI 1.4-5.0, P = 0.003), but not when adjusted for exercise dose and age (adjusted OR 1.8, 95% CI 0.9-3.6, P = 0.12 and 1.5, 95% CI 0.7-3.1, P = 0.30, by 5 MET-h/week increments). In all, 167 (88%) patients had ≥2 echocardiographic examinations during 6.9 (IQR 4.7-9.8) years of follow-up. We observed no sex differences in deterioration of right or left ventricular dimensions and functions. CONCLUSION: Male AC patients were more often probands and had higher prevalence of VA than female patients, but not when adjusting for exercise dose. Importantly, disease progression was similar between male and female patients.

EACVI recommendations on cardiovascular imaging for the detection of embolic sources: endorsed by the Canadian Society of Echocardiography.

Cardioaortic embolism to the brain accounts for approximately 15-30% of ischaemic strokes and is often referred to as 'cardioembolic stroke'. One-quarter of patients have more than one cardiac source of embolism and 15% have significant cerebrovascular atherosclerosis. After a careful work-up, up to 30% of ischaemic strokes remain 'cryptogenic', recently redefined as 'embolic strokes of undetermined source'. The diagnosis of cardioembolic stroke remains difficult because a potential cardiac source of embolism does not establish the stroke mechanism. The role of cardiac imaging-transthoracic echocardiography (TTE), transoesophageal echocardiography (TOE), cardiac computed tomography (CT), and magnetic resonance imaging (MRI)-in the diagnosis of potential cardiac sources of embolism, and for therapeutic guidance, is reviewed in these recommendations. Contrast TTE/TOE is highly accurate for detecting left atrial appendage thrombosis in patients with atrial fibrillation, valvular and prosthesis vegetations and thrombosis, aortic arch atheroma, patent foramen ovale, atrial septal defect, and intracardiac tumours. Both CT and MRI are highly accurate for detecting cavity thrombosis, intracardiac tumours, and valvular prosthesis thrombosis. Thus, CT and cardiac magnetic resonance should be considered in addition to TTE and TOE in the detection of a cardiac source of embolism. We propose a diagnostic algorithm where vascular imaging and contrast TTE/TOE are considered the first-line tool in the search for a cardiac source of embolism. CT and MRI are considered as alternative and complementary tools, and their indications are described on a case-by-case approach.

The cardiac impact of cisplatin-based chemotherapy in survivors of testicular cancer: a 30-year follow-up.

AIMS: Cisplatin-based chemotherapy (CBCT) is essential in the treatment of metastatic testicular cancer (TC) but has been associated with long-term risk of cardiovascular morbidity and mortality. Furthermore, cisplatin can be detected in the body decades after treatment. We aimed to evaluate the long-term impact of CBCT on cardiac function and morphology in TC survivors 30 years after treatment. METHODS AND RESULTS: TC survivors treated with CBCT (1980-94) were recruited from the longitudinal Norwegian Cancer Study in Testicular Cancer Survivors and compared with a control group matched for sex, age, smoking status, and heredity for coronary artery disease. All participants underwent laboratory tests, blood pressure measurement, and 2D and 3D echocardiography including 2D speckle-tracking strain analyses. Ninety-four TC survivors, on average 60 ± 9 years old, received a median cumulative cisplatin dose of 780 mg (IQR 600-800). Compared with controls, TC survivors more frequently used anti-hypertensive (55% vs. 24%, P < 0.001) and lipid-lowering medication (44% vs. 18%, P < 0.001). TC survivors had worse diastolic function parameters with higher E/e'-ratio (9.8 ± 3.2 vs. 7.7 ± 2.5, P < 0.001), longer mitral deceleration time (221 ± 69 vs. 196 ± 57ms, P < 0.01), and higher maximal tricuspid regurgitation velocity (25 ± 7 vs. 21 ± 4 m/s, P = 0.001). The groups did not differ in left or right ventricular systolic function, prevalence of arrhythmias, or valvular heart disease. Cumulative cisplatin dose did not correlate with cardiac parameters. CONCLUSION: No signs of overt or subclinical reduction in systolic function were identified. Long-term cardiovascular adverse effects three decades after CBCT may be limited to metabolic dysfunction and worse diastolic function in TC survivors.

Mitral annulus disjunction is associated with adverse outcome in Marfan and Loeys-Dietz syndromes.

AIMS: We aimed to assess the prevalence of mitral annulus disjunction (MAD) and to explore the association with aortic disease and mitral valve surgery in patients with Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS). METHODS AND RESULTS: We included consecutive MFS patients fulfilling Revised Ghent Criteria and LDS patients fulfilling Loeys-Dietz Revised Nosology. MAD was identified by echocardiography and was quantified as the longitudinal distance from the ventricular myocardium to the hinge point of the posterior mitral leaflet. Aortic events were defined as aortic dissection or prophylactic aortic surgery. We recorded the need of mitral valve surgery including mitral valve repair or replacement. We included 168 patients (103 with MFS and 65 with LDS). The prevalence of MAD was 41%. MAD was present in all age groups. Aortic events occurred in 112 (67%) patients (27 with dissections and 85 with prophylactic surgical interventions). Patients with MAD were younger at aortic event than those without MAD (log rank = 0.02) Patients with aortic events had greater MAD distance in posterolateral wall [8 (7-10) mm vs. 7 (6-8) mm, P = 0.04]. Mitral events occurred more frequently in patients with MAD (P < 0.001). CONCLUSION: MAD was highly prevalent in patients with MFS and LDS. MAD was a marker of severe disease including aortic events at younger age and need of mitral valve surgery. Screening patients with MFS an LDS for MAD may provide prognostic information and may be relevant in planning surgical intervention. Detection of MAD in patients with MFS and LDS may infer closer clinical follow-up from younger age.

Pregnancies, ventricular arrhythmias, and substrate progression in women with arrhythmogenic right ventricular cardiomyopathy in the Nordic ARVC Registry.

AIMS: Women with arrhythmogenic right ventricular cardiomyopathy (ARVC) are at relatively lower risk of ventricular arrhythmias (VAs) than men, but the physical burden associated with pregnancy on VA risk remains insufficiently studied. We aimed to assess the risk of VA in relation to pregnancies in women with ARVC. METHODS AND RESULTS: We included 199 females with definite ARVC (n = 121) and mutation-positive family members without ascertained ARVC diagnosis (n = 78), of whom 120 had at least one childbirth. Ventricular arrhythmia-free survival after the latest childbirth was compared between women with one (n = 20), two (n = 67), and three or more (n = 37) childbirths. Cumulative probability of VA for each pregnancy (n = 261) was assessed from conception through 2 years after childbirth and compared between those pregnancies that occurred before (n = 191) or after (n = 19) ARVC diagnosis and in mutation-positive family members (n = 51). The nulliparous women had lower median age at ARVC diagnosis (38 vs. 42 years, P < 0.001) and first VA (22 vs. 41 years, P < 0.001). Ventricular arrhythmia-free survival after the latest childbirth was not related to the number of pregnancies. No pregnancy-related VA was reported among the family members. Women who gave birth after ARVC diagnosis had elevated risk of VA postpartum (hazard ratio 13.74, 95% confidence interval 2.9-63, P = 0.001), though only two events occurred during pregnancies. CONCLUSION: In women with ARVC, pregnancy was uneventful for the overwhelming majority and the number of prior completed pregnancies was not associated with VA risk. Pregnancy-related VA was primarily related to the phenotypical severity rather than pregnancy itself.

Role of cardiovascular imaging in cancer patients receiving cardiotoxic therapies: a position statement on behalf of the Heart Failure Association (HFA), the European Association of Cardiovascular Imaging (EACVI) and the Cardio-Oncology Council of the European Society of Cardiology (ESC).

Cardiovascular (CV) imaging is an important tool in baseline risk assessment and detection of CV disease in oncology patients receiving cardiotoxic cancer therapies. This position statement examines the role of echocardiography, cardiac magnetic resonance, nuclear cardiac imaging and computed tomography in the management of cancer patients. The Imaging and Cardio-Oncology Study Groups of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in collaboration with the European Association of Cardiovascular Imaging (EACVI) and the Cardio-Oncology Council of the ESC have evaluated the current evidence for the value of modern CV imaging in the cardio-oncology field. The most relevant echocardiographic parameters, including global longitudinal strain and three-dimensional ejection fraction, are proposed. The protocol for baseline pre-treatment evaluation and specific surveillance algorithms or pathways for anthracycline chemotherapy, HER2-targeted therapies such as trastuzumab, vascular endothelial growth factor tyrosine kinase inhibitors, BCr-Abl tyrosine kinase inhibitors, proteasome inhibitors and immune checkpoint inhibitors are presented. The indications for CV imaging after completion of oncology treatment are considered. The typical consequences of radiation therapy and the possibility of their identification in the long term are also summarized. Special populations are discussed including female survivors planning pregnancy, patients with carcinoid disease, patients with cardiac tumours and patients with right heart failure. Future directions and ongoing CV imaging research in cardio-oncology are discussed.