Cardiovascular and non-renal complications of chronic kidney disease: Managing risk.

Chronic kidney disease (CKD) currently affects approximately 850 million people globally and is continuing to increase in prevalence as well as in importance as a cause of death. The excess mortality related to CKD is mostly caused by an increase in cardiovascular disease. This includes atherosclerotic cardiovascular disease as many promoters of atherosclerosis, such as blood pressure, lipid levels and hypercoagulation, are increased in people with CKD. Diabetes is a leading cause of CKD contributing to the risk of CVD, and obesity is also increasingly prevalent. Management of these risk factors is therefore very important in CKD, and to reduce risk of CKD progression. Heart failure is also more prevalent in CKD and, again, many risk factors are shared. The concept of foundational pillars in the management of heart failure has been adapted to the treatment of CKD, with many organ-protective interventions, such renin-angiotensin system blockade, sodium-glucose cotransporter-2 inhibition and mineralocorticoid receptor antagonism, reducing the risk for mortality in heart failure with reduced ejection fraction, but also for progression of CKD. Atrial fibrillation is also more common with CKD and affects the management of the former. In this review these non-renal complications of CKD are discussed, along with how the risk of these complications should be managed. Many new opportunities have demonstrated heart and kidney organ protection, but implementation is a challenge.

Trends in percutaneous left atrial appendage occlusion and 1-year mortality 2013-2021: A nationwide observational study.

BACKGROUND: Percutaneous left atrial appendage occlusion (LAAO) is increasingly used for stroke prevention in patients with atrial fibrillation and anticoagulant-related complications. Yet, real-life studies evaluating changes in patient characteristics and indications for LAAO remain scarce. METHODS: To evaluate changes in patient characteristics and indications for LAAO defined as 2-year history of intracerebral bleeding, any ischemic stroke/systemic embolism (SE), any non-intracerebral bleeding, other indication, and 1-year mortality. All patients undergoing percutaneous LAAO in Denmark from 2013 to 2021 were stratified into the following year groups: 2013-2015, 2016-2018, and 2019-2021. RESULTS: In total, 1465 patients underwent LAAO. Age remained stable (2013-2015: 74 years versus 2019-2021: 75 years). Patients' comorbidity burden declined, exemplified by CHA2DS2-VASc ≥4 and HAS-BLED ≥3 decreased from 56.7% and 63.7% in 2013-2015 to 40.3% and 45.8% in 2019-2021. Indications for LAAO changed over time with other indication comprising 44.7% in 2019-2021; up from 26.9% in 2013-2015. Conversely, fewer patients had an indication of any ischemic stroke/SE (2013-2015: 30.8% vs 2019-2021: 20.3%) or any non-intracerebral bleeding (2013-2015: 29.4% vs 2019-2021: 23.4%). 1-year mortality was 11.3% for any non-intracerebral bleeding and 6.2% for other indication. CONCLUSION: The LAAO patient-profile has changed considerably. Age remained stable, while comorbidity burden decreased during the period 2013-2021. LAAO is increasingly used in patients with no clinical event history and mortality differs according to indication. Selection of patients to LAAO should be done carefully, and contemporary real-life studies investigating clinical practice could add important insights.

Physician perceptions, attitudes, and strategies towards implementing guideline-directed medical therapy in heart failure with reduced ejection fraction. A survey of the Heart Failure Association of the ESC and the ESC Council for Cardiology Practice.

AIMS: Recent guidelines recommend four core drug classes (renin-angiotensin system inhibitor/angiotensin receptor-neprilysin inhibitor [RASi/ARNi], beta-blocker, mineralocorticoid receptor antagonist [MRA], and sodium-glucose cotransporter 2 inhibitor [SGLT2i]) for the pharmacological management of heart failure (HF) with reduced ejection fraction (HFrEF). We assessed physicians' perceived (i) comfort with implementing the recent HFrEF guideline recommendations; (ii) status of guideline-directed medical therapy (GDMT) implementation; (iii) use of different GDMT sequencing strategies; and (iv) barriers and strategies for achieving implementation. METHODS AND RESULTS: A 26-question survey was disseminated via bulletin, e-mail and social channels directed to physicians with an interest in HF. Of 432 respondents representing 91 countries, 36% were female, 52% were aged <50 years, and 90% mainly practiced in cardiology (30% HF). Overall comfort with implementing quadruple therapy was high (87%). Only 12% estimated that >90% of patients with HFrEF without contraindications received quadruple therapy. The time required to initiate quadruple therapy was estimated at 1-2 weeks by 34% of respondents, 1 month by 36%, 3 months by 24%, and ≥6 months by 6%. The average respondent favoured traditional drug sequencing strategies (RASi/ARNi with/followed by beta-blocker, and then MRA with/followed by SGLT2i) over simultaneous initiation or SGLT2i-first sequences. The most frequently perceived clinical barriers to implementation were hypotension (70%), creatinine increase (47%), hyperkalaemia (45%) and patient adherence (42%). CONCLUSIONS: Although comfort with implementing all four core drug classes in patients with HFrEF was high among physicians, a majority estimated implementation of GDMT in HFrEF to be low. We identified several important perceived clinical and non-clinical barriers that can be targeted to improve implementation.

Infrequent transition to direct oral anticoagulants in patients with cancer.

INTRODUCTION: Pharmacokinetic drug-drug interactions (DDIs) are challenging aspects of direct oral anticoagulant (DOAC) therapy in patients with cancer. We evaluated the prevalence of potential DOAC/antineoplastic agent DDIs and the one-year cumulative incidence of switching from low-molecular-weight heparin (LMWH) to a DOAC in patients with cancer. METHODS: Patients with cancer and an indication of LMWH were included from Herlev and Gentofte Hospital, Denmark, in the 2014-2019 period. Follow-up was initiated when the first dose of LMWH was dispensed. Data were obtained from electronic medical records. One-year cumulative incidence of switching from LMWH to DOAC was estimated using the Aalen-Johansen estimator. Potential DDIs were evaluated using a report from the European Heart Rhythm Association (EHRA) and a review by Hellfritzsch et al. RESULTS. A total of 161 patients were included with a median age of 70.8 (interquartile range: 64.2-76.1) years. The one-year cumulative incidence of switching from LMWH to DOAC was 32% (95% confidence intervals: 21-43%) in patients eligible for DOACs. Using the EHRA report, a total of 24% of antineoplastic agents were not identified. This percentage decreased to 8% using data from Hellfritzsch et al. CONCLUSIONS. In patients with cancer, the one-year cumulative incidence of switching from LMWH to DOAC was less-t 35% in patients eligible for DOAC, revealing a potential for improved anticoagulant treatment. Furthermore, contemporary data elaborated on potential DDIs between DOACs/antineoplastic agents. FUNDING: "Helsefonden" (21-B-0350) and the "Karen Elise Jensens Fonden" (29-4-2021) funded the study. TRIAL REGISTRATION: Not relevant.

Short- and Long-Term Mortality for Patients With and Without a Cancer Diagnosis Following Pulmonary Embolism in Denmark, 2000 to 2020: A Nationwide Study.

BACKGROUND: New treatment regimens have been introduced in the past 20 years, which may influence the short- and long-term prognosis for patients with and without a cancer diagnosis following pulmonary embolism. However, newer studies investigating these trends are lacking. Therefore, we aimed to investigate the 30- and 31- to 365-day mortality following pulmonary embolism. METHODS AND RESULTS: Using the Danish nationwide registries, patients with a diagnosis of pulmonary embolism between 2000 and 2020 were included. Age- and sex-standardized 30- and 31- to 365-day mortality was calculated and stratified by cancer status. In total, 60 614 patients (29.6% with recent cancer; mean age, 68.2 years) were included. The 30-day mortality for patients with no recent cancer decreased from 19.1% (95% CI, 17.9%-20.4%) in 2000 to 7.3% (95% CI, 6.7%-8.0%) in 2018 to 2020 (hazard ratio [HR], 0.36 [95% CI, 0.32-0.40]; P<0.001). The 30-day mortality for patients with recent cancer decreased from 32.2% (95% CI, 28.8%-36.6%) to 14.1% (95% CI, 12.7%-15.5%) (HR, 0.38 [95% CI, 0.33-0.44]; P<0.001). The 31- to 365-day mortality for patients with no recent cancer decreased from 12.5% (95% CI, 11.4%-13.6%) to 9.4% (95% CI, 8.6%-10.2%) (HR, 0.73 [95% CI, 0.64-0.83]; P<0.001).The 31- to 365-day mortality for patients with recent cancer remained stable: 39.4% (95% CI, 35.1%-43.7%) to 38.3% (95% CI, 35.9%-40.6%) (HR, 0.97 [95% CI, 0.84-1.12]; P=0.69). CONCLUSIONS: From 2000 to 2020, improvements were observed in 30-day mortality following pulmonary embolism regardless of cancer status. For patients with recent cancer, 31- to 365-day mortality did not improve, whereas a minor improvement was observed for patients without recent cancer.

High risk of rehospitalization within one year following a pulmonary embolism-Insights from the Danish nationwide registries from 2000-2020.

AIM: To identify the absolute risk, causes and factors associated with rehospitalization within 1 year of discharge with a pulmonary embolism (PE). METHODS AND RESULTS: Using the Danish nationwide registries, all patients admitted with a first-time PE between 2000 and 2020 and discharged alive were included. Subsequent hospitalizations were categorized and crude cumulative incidences, were used to estimate the absolute risk (AR) of any rehospitalization and specific causes of rehospitalizations. Risk factors for rehospitalization were investigated using cause specific Cox regression models.A total of 55 201 patients were identified. The median age of the study population was 70 years (inter quartile range: 59;79), and the most prevalent comorbidities were cancer (29.3%) and ischemic heart disease (12.7%). The 1-year AR of any rehospitalization after discharge with a PE was 48.6% (95% confidence interval (CI); 48.2%-48.8%). The most common cause for being rehospitalized was due to respiratory disease (1-year AR: 9.5% (95% CI: 9.3%-9.8%)), followed by cardiovascular disease (1-year AR: 6.3% (95% CI: 5.9%-6.5%)), cancer (1-year AR: 6.0% (95% CI: 5.8%-6.4%)), venous thromboembolism (1-year AR: 5.2% (95% CI: 5.0%-5.2%)), and symptom diagnoses (1-year AR: 5.2% (95%CI: 5.0%-5.4%)). Factors that were associated with an increased risk of rehospitalization were cancer, liver disease, chronic obstructive pulmonary disease, chronic kidney disease, and immobilization. CONCLUSION: Patients with PE have a high risk of rehospitalization, with almost half of patients being rehospitalized within 1 year. Identification of high-risk patients may help target interventions aiming at reducing the risk of rehospitalization.

Effect on cardiac function among patients with type 2 diabetes following high-dose mineralocorticoid receptor antagonist using echocardiography; data from the MIRAD randomized clinical trial.

BACKGROUND: Early heart failure prevention is central in patients with type 2 diabetes, and mineralocorticoid receptor antagonists (MRAs) have shown to improve prognosis. We investigated the effect of high-dose MRA, eplerenone, on cardiac function and structure in patients with type 2 diabetes and established or increased risk of cardiovascular disease but without heart failure. METHODS: In the current randomized, placebo-controlled clinical trial, 140 patients with high-risk type 2 diabetes were randomized to high-dose eplerenone (100-200 mg daily) or placebo as add-on to standard care for 26 weeks. Left ventricular systolic and diastolic function, indexed left ventricular mass (LVMi), and global longitudinal strain (GLS) were assessed using echocardiography at baseline and after 26 weeks of treatment. RESULTS: Of the included patients, 138 (99%) had an echocardiography performed at least once. Baseline early diastolic in-flow velocity (E-wave) indexed by mitral annulus velocity (e') was mean (SD) 11.1 (0.5), with 31% of patients reaching above 12. No effect of treatment on diastolic function was observed measured by E/e' (0.0, 95%CI [-1.2 to 1.2], P = 0.992) or E/A (-0.1, 95%CI [-0.2 to 0.0], P = 0.191). Mean left ventricular ejection fraction (LVEF) at baseline was 59.0% (8.0). No improvement in systolic function was observed when comparing groups after 26 weeks (LVEF: 0.9, 95%CI [-1.1 to 2.8], P = 0.382; GLS: -0.4%, 95%CI [-1.5 to 0.6], P = 0.422), nor in LVMi (-3.8 g/m2 95%CI [-10.2 to 2.7], P = 0.246). CONCLUSION: In the present echo sub-study, no change in left ventricular function was observed following high-dose MRA therapy in patients with type 2 diabetes when evaluated by conventional echocardiography. TRIAL REGISTRATION: Date of registration 25/08/2015 (EudraCT number: 2015-002,519-14).

"No one told me anything about it and I cannot explain it": Illness perception in symptomatic and asymptomatic patients with cancer-associated thrombosis.

INTRODUCTION: Patients with cancer, have reported cancer-associated thrombosis (CAT), a distressing event in their overall illness. However, whether the clinical presentation of CAT; symptomatic versus asymptomatic, impacts illness perception is poorly elucidated. The aim of this study was to explore illness perception in patients with CAT, stratified by the clinical presentation. MATERIALS AND METHODS: In a qualitative design, we conducted a three-step workshop. Patients were included from a specialised cardiology care unit for oncology patients. Data analysis was performed using framework analysis. The analytic framework was based on the five components of illness perception: (1) identity of illness, (2) causal beliefs, (3) timeline beliefs, (4) beliefs about control/cure and (5) consequences. RESULTS: Elleven patients with CAT participated in the workshop; five symptomatic and six asymptomatic. Whitin each category of illness perception following notions emerged (1) the identity of CAT was only tangible for symptomatic participants, (2) the aetiology was considered important information for symptomatic participants, which was in contrast to asymptomatic participants, (3) asymptomatic participant did not consider recurrent CAT a threat towards their health, (4) asymptomatic participants were prone to information overload, whilst information was imperative to the sense of control in symptomatic participants, (5) low molecular weight heparin treatment was accepted in symptomatic participants due to remission of symptoms. CONCLUSIONS: The clinical presentation of CAT (asymptomatic/symptomatic) proved essential to illness perception. These findings indicate that information level and communication within the medical consultation, should actively consider the clinical presentation of CAT in order to optimize management and compliance.

Percutaneous left atrial appendage occlusion discrepancy between randomised trials and clinical practice.

In patients with atrial fibrillation and previous episodes of bleeding on oral anticoagulant treatment, left atrial appendage occlusion (LAAO) has emerged as an alternative way to decrease the risk of stroke.The use of the procedure has been on the rise, and the news coverage has been dominated by an uncritical acceptance of the benefit of this procedure, which probably have contributed to the increasing number of procedures.This commentary is a presentation and critical appraisal of the available evidence on the efficacy and safety of left atrial appendage closure as stroke prophylaxis.We illustrate that LAAO is supported by limited randomised data risk of serious complications, which we do not believe supports the current widespread use.

Real-life incidence of cardiotoxicity and associated risk factors in sarcoma patients receiving doxorubicin.

BACKGROUND: Anthracycline induced cardiotoxicity is well recognized but only few data exist in sarcoma patients. This study retrospectively aimed to analyze sequential Cadmium Zinc Telluride (CZT)-multigated equilibrium radionuclide angiography (ERNA) for monitoring left ventricular ejection fraction (LVEF) and to assess the real-life incidence of cardiotoxicity in sarcoma patients receiving doxorubicin based chemotherapy. MATERIALS AND METHODS: A retrospective analysis was performed on all sarcoma patients referred to Herlev University Hospital between 2012 and 2015. Cardiotoxicity was defined as a decline in LVEF of > 10% percentage point to a LVEF < 50% as compared to baseline. Early cardiotoxicity was defined as < 1 year and late cardiotoxicity as ≥ 1 year. Recovery of cardiotoxicity was defined as a LVEF ≥ 50%. RESULTS: A total of 149 patients were referred, 75 (50%) sarcoma patients were included. The main reason for exclusion was that only one CZT-ERNA had been performed in 50 (68%) of the patients. Twenty-three (31%) of the patients experienced cardiotoxicity, 11 (48%) were female, mean age was 56.9 years. Early cardiotoxicity was observed in 16 (70%) of the patients and 11 (48%) experienced clinical symptoms of cardiotoxicity at diagnosis. Recovery of LVEF was seen in 12 (55%) of the patients and persistent recovery in 10 (45%). The diastolic blood pressure at baseline was positively and significantly associated with a higher risk of developing cardiotoxicity (Relative Risk (RR): 1.039 (95% CI= 1.001 - 1.079; p = 0.042)). The median survival was 1.4 years (range 0.5 - 2.2 years) for patients with metastatic disease versus 3.9 years (range 1.5 - 6.4 years) (p = 0.009) for localized disease at baseline. CONCLUSION: Cardiotoxicity is a relative frequent complication in sarcoma patients treated with doxorubicin based chemotherapy and the diastolic blood pressure at baseline was significantly associated with a higher risk of developing cardiotoxicity.

Cardiovascular disease in women with breast cancer - a nationwide cohort study.

BACKGROUND: There is increasing concern about cardiovascular disease (CVD) after breast cancer (BC). The aim of this study was to estimate the prevalence of different types of CVD in women diagnosed with BC compared to cancer-free controls as well as the incidence of CVD after BC diagnosis. METHODS: We performed a cohort study based on data from national registries covering the entire Danish population. We followed 16,505 cancer-naïve BC patients diagnosed from 2003 to 2007 5 years before and up to 10 years after BC diagnosis compared to 165,042 cancer-free controls. RESULTS: We found that 15.6% of BC patients were registered with at least one CVD diagnosis in hospital records before BC diagnosis. Overall, BC patients and controls were similar with regard to CVD comorbidity before BC diagnosis. After BC diagnosis, the incidence of all CVD diagnoses combined was significantly higher in BC patients than controls up to approximately 6 years after the index date (BC diagnosis). After 10 years, 28% of both BC patients and controls (without any CVD diagnosis up to 5 years before the index date) had at least one CVD diagnosis according to hospital records. However, the incidence of heart failure, thrombophlebitis/thrombosis and pulmonary heart disease including pulmonary embolism remained higher in BC patients than controls during the entire 10-year follow-up period. After 10 years, 2.7% of BC patients compared to 2.5% of controls were diagnosed with heart failure, 2.7% of BC patients compared to 1.5% of controls were diagnosed with thrombophlebitis/thrombosis, and 1.5% of BC patients compared to 1.0% of controls were diagnosed with pulmonary heart disease according to hospital records. Furthermore, we found that the risk of heart failure and thrombophlebitis/thrombosis was higher after chemotherapy. CONCLUSIONS: Focus on CVD in BC patients is important to ensure optimum treatment with regard to BC as well as possible CVD. Strategies to minimise and manage the increased risk of heart failure, thrombophlebitis/thrombosis and pulmonary heart disease including pulmonary embolism in BC patients are especially important.

Mortality from cardiovascular disease in women with breast cancer - a nationwide registry study.

BACKGROUND: Only few existing studies have investigated the mortality from cardiovascular disease (CVD) in women with breast cancer (BC). The aim of this study was to investigate CVD mortality in patients with BC compared with a matched control group without BC using national registry data. MATERIAL AND METHODS: We followed 16,505 Danish women diagnosed with BC in 2003-2007 up to 10 years after BC diagnosis compared with 165,042 matched controls from the general Danish population. The matching criteria included gender, age, region of residence, and education. We performed multivariate Cox regression analyses to investigate the influence of preexisting CVD on mortality. Moreover, we used the cumulative incidence and conditional probability functions to study the risk of CVD-related death in the presence of competing risk, i.e., the risk of dying from other causes than CVD. RESULTS: We found that preexisting CVD increased both overall mortality and CVD mortality in both patients with BC and controls. Furthermore, we found that patients with BC were at lower risk of dying from CVD up to 10 years after BC diagnosis compared with controls. The cumulative incidence of CVD as underlying cause of death was 4.0% in patients with BC and 5.7% in controls after 10 years. The most common CVD-related causes of death were ischemic heart disease including acute coronary syndrome, cerebrovascular accident, heart failure, and atrial fibrillation. DISCUSSION: Our study contributes to the growing body of work on BC and comorbidities and highlights the importance of CVD in individuals with BC. Further studies are needed to confirm our finding that patients with BC are at lower risk of dying from CVD up to 10 years after BC diagnosis compared with a matched control group without BC.

Management of Cancer-Associated Venous Thrombosis: A Nationwide Survey among Danish Oncologists.

Background Treatment patterns for cancer-associated venous thrombosis (CAT) has been shown to be nonconsistent with contemporary guideline recommendations, resulting in poor patient outcomes. Objectives The study aimed to describe contemporary CAT management in Danish oncology departments and identify knowledge gaps and inconsistencies between guidelines and clinical practice. Patients and Methods A survey questionnaire in Danish was developed based on contemporary national guidelines. Using an open recruitment strategy, invitations to participate in the electronic survey were sent to physicians employed at oncology departments in Denmark in winter of 2018/2019. The questionnaire was based on current national guidelines and included 10 items with multiple choices and a free-text option to specify or comment. The questionnaire was pilot-tested by a junior and senior oncologist. Results A total of 142 physicians completed the survey, representing all Danish geographical regions and various seniority. The majority reported that CAT was treated and followed up in oncology departments. However, 36.6% of the physicians were unaware of the existence of designated cancer thrombosis guidelines. Risk of venous thrombosis was generally assessed without diagnostic scores. Almost all (98.6%) reported low-molecular-weight heparin to be first-line treatment for CAT. Treatment duration seemed wrongly influenced by subtype of venous thrombosis, and 44.5% responded that thromboprophylaxis among hospitalized patients was substantially underused. Conclusion The variability in the daily clinical management of CAT demonstrated through this survey indicates a potential to increase awareness of available guidelines, standardized use of inpatient thromboprophylaxis, and organized treatment and follow-up in a multidisciplinary setting, which would potentially improve management of CAT in Denmark.

[Venous thromboembolism in patients with COVID-19].

The importance of venous thromboembolism (VTE) as a major complication in patients with severe corona virus disease 2019 (COVID-19) is becoming increasingly evident. In this review, we describe the proposed pathophysiology of the prothrombotic coagulation changes observed in patients with COVID-19. Further, based on a review of the currently available evidence on VTE prevalence in patients with COVID-19, we present and discuss the recommendations from the Danish Society of Thrombosis and Haemostasis on the use of thromboprophylaxis in patients with COVID-19.

[Acral ischaemia with multiple microthromboses and imminent gangrene in a 73-year-old woman with COVID-19].

This is a report of an atypical presentation of COVID-19. The patient had sparse pulmonary symptoms despite characteristic COVID-19 lesions on CT-thorax and developed severe acral ischaemic change, after a few days of hospitalisation. The condition could not be explained by classical sepsis with hypotension and hypoperfusion, disseminated intravascular coagulation, vasculitis, endocarditis or severe peripheral arteriosclerosis. A skin biopsy showed microthrombosis, interpreted as an activation of the coagulation system associated with COVID-19. Apparently, there are multiple COVID-19 phenotypes.

Early Stages of Obesity-related Heart Failure Are Associated with Natriuretic Peptide Deficiency and an Overall Lack of Neurohormonal Activation: The Copenhagen Heart Failure Risk Study.

Objective: This study evaluated the associations between the natriuretic peptide activity and the neurohormonal response in non-obese and obese outpatients with and without heart failure (HF). Background: Obesity-related HF may be a distinct subtype of HF. Obesity is associated with lower plasma concentrations of natriuretic peptides. The associations between obesity and neurohormonal activation estimated by mid-regional pro-adrenomedullin (MR-proADM) and copeptin in patients with HF is not elucidated. Methods: This prospective cohort-study included 392 outpatients ≥60years, plus ≥1 risk-factor(-s) for HF (hypertension, ischemic heart disease, atrial fibrillation, diabetes, chronic kidney disease), and without known HF. Patients were categorized 'non-obese' BMI = 18.5-29.9 kg/m2 (n = 273) and 'obese' BMI ≥ 30 kg/m2 (n = 119). The diagnosis of HF required signs, symptoms, and abnormal echocardiography. NT-proBNP, MR-proANP, MR-proADM, and copeptin were analyzed. Results: Obese patients were younger, had a higher prevalence of diabetes and chronic kidney disease, but a lower prevalence of atrial fibrillation. A total of 39 (14.3%) non-obese and 26 (21.8%) obese patients were diagnosed with HF. In obese patients, HF was not associated with higher plasma concentrations of NT-proBNP (Estimate: 0.063; 95%CI: -0.037-1.300; P = 0.064), MR-proANP (Estimate: 0.207; 95%CI: -0.101-0.515; P = 0.187), MR-proADM (Estimate: 0.112; 95%CI: -0.047-0.271; P = 0.168), or copeptin (Estimate: 0.093; 95%CI: -0.333-0.518; P = 0.669). Additionally, obese patients with HF had lower plasma concentrations of NT-proBNP (Estimate: -0.998; 95%CI: -1.778-0.218; P = 0.012), and MR-proANP (Estimate: -0.488; 95%CI: -0.845-0.132; P = 0.007) compared to non-obese patients with HF, whereas plasma concentrations of MR-proADM (Estimate: 0.066; 95%CI: -0.119-0.250; P = 0.484) and copeptin (Estimate: 0.140; 95%CI: -0.354-0.633; P = 0.578) were comparable. Conclusions: Patients with obesity-related HF have natriuretic peptide deficiency and lack of increased plasma concentrations of MR-proADM and copeptin suggesting that patients with obesity-related HF have a blunted overall neurohormonal activity.

Diagnostic utility of MR-proANP and NT-proBNP in elderly outpatients with a high risk of heart failure: the Copenhagen heart failure risk study.

Background: Amino-terminal-pro-B-type-natriuretic-peptide (NT-proBNP) is a diagnostic biomarker for heart failure (HF), but plasma concentrations are influenced by numerous factors. Mid-regional-pro-atrial-natriuretic-peptide (MR-proANP) have comparable diagnostic value in acute HF. However, data are lacking in the non-acute setting. This study sought to assess the diagnostic utility of MR-proANP in outpatients with a high risk of HF.Methods: This prospective study included 399 outpatients. Inclusion criteria were: age ≥ 60 years, ≥1 risk factor for HF (diabetes, chronic kidney disease, vascular disease, atrial fibrillation, hypertension), without known or suspected HF. Unrecognized HF was diagnosed based on clinical signs, patient-reported symptoms and echocardiography. Plasma concentrations of MR-proANP and NT-proBNP were analysed.Results: In total, 65 patients were diagnosed with HF or asymptomatic left ventricular systolic dysfunction (N = 12 LVEF ≤ 40%, N = 7 LVEF > 40% to ≤50%, N = 46 LVEF > 50%). Both MR-proANP (odds-ratio: 1.77; 95% CI:1.16-2.72; p = 0.009) and NT-proBNP (odds-ratio: 1.49; 95% CI:1.22-1.82; p < 0.001) were associated with HF. Area under receiver-operator characteristics curve (AUC) for the diagnosis of HF or asymptomatic left ventricular systolic dysfunction was higher for MR-proANP (AUC = 0.886; p < 0.001) and NT-proBNP (AUC = 0.910; p < 0.001) compared to patient-reported symptoms of HF (AUC = 0.830), but NT-proBNP added more diagnostic information compared to MR-proANP (p = 0.022).Conclusions: Both NT-proBNP and MR-proANP are useful biomarkers in the diagnosis of HF or asymptomatic left ventricular systolic dysfunction in a non-acute setting. However, NT-proBNP added more diagnostic information compared to MR-proANP.

Incidence and risk markers of 5-fluorouracil and capecitabine cardiotoxicity in patients with colorectal cancer.

Background: Fluoropyrimidines are mainstay chemotherapeutics in the treatment of gastrointestinal cancers and are also used to treat breast cancer and head and neck cancers. However, 5-flourouracil (5-FU) and capecitabine may induce cardiotoxicity that mostly presents as acute coronary syndromes. We compared the incidence of cardiotoxicity induced by 5-FU and capecitabine in patients with colorectal cancer and sought to identify risk markers for cardiotoxicity.Methods: We reviewed all consecutive patients with colorectal cancer who received 5-FU or capecitabine at one institution in the neoadjuvant (2007-2016), adjuvant (2000-2016) or metastatic setting (2007-2016).Results: Totally, 995 patients received 5-FU and 1241 received capecitabine. The incidence of cardiotoxicity induced by 5-FU was 5.2% [95% confidence interval (CI): 3.8-6.6%] and 4.1% (95% CI: 3.0-5.2%) induced by capecitabine (p = .21). The most common events were angina without ischemia (5-FU: 1.6%, capecitabine: 1.3%, p = .53), angina with ischemia on ECG (5-FU: 0.9%, capecitabine: 0.8%, p = .53), unspecified chest pain (5-FU: 0.9%, capecitabine: 0.6%, p = .34), ST-elevation myocardial infarction (5-FU: 0.5%; capecitabine: 0.4%, p = .76) and non-ST-elevation myocardial infarction (5-FU: 0.7%, capecitabine: 0.5%, p = .50). Cardiac arrest or sudden death occurred in 0.5 and 0.4%, respectively (p = 1). No risk markers for cardiotoxicity induced by 5-FU were identified. In the capecitabine group, ischemic heart disease was a risk marker (odds ratio: 2.9, 95% CI: 1.2-7.0, p = .016).Conclusions: Five percent of patients treated with 5-FU developed cardiotoxicity and 4% treated with capecitabine. Ischemic heart disease was a risk marker for cardiotoxicity induced by capecitabine.

One-year outcomes in atrial fibrillation presenting during infections: a nationwide registry-based study.

AIMS: Thromboprophylaxis guidelines for patients with concurrent atrial fibrillation (AF) during infections are unclear and not supported by data. We compared 1-year outcomes in patients with infection-related AF and infection without AF. METHODS AND RESULTS: By crosslinking Danish nationwide registry data, AF naïve patients admitted with infection (1996-2016) were identified. Those with AF during the infection (infection-related AF) were matched 1:3 according to age, sex, type of infection, and year with patients with infection without AF. Outcomes (AF, thromboembolic events) were assessed by multivariable Cox regression. The study population comprised 30 307 patients with infection-related AF and 90 912 patients with infection without AF [median age 79 years (interquartile range 71-86), 47.6% males in both groups]. The 1-year absolute risk of AF and thromboembolic events were 36.4% and 7.6%, respectively (infection-related AF) and 1.9% and 4.4%, respectively (infection without AF). In the multivariable analyses, infection-related AF was associated with an increased long-term risk of AF and thromboembolic events compared with infection without AF: hazard ratio (HR) 25.98, 95% confidence interval (CI) 24.64-27.39 for AF and HR 2.10, 95% CI 1.98-2.22 for thromboembolic events. Further, differences in risks existed across different subtypes of infections. CONCLUSION: During the first year after discharge, 36% of patients with infection-related AF had a new hospital contact with AF. Infection-related AF was associated with increased risk of thromboembolic events compared with infection without AF and our results suggest that AF related to infection may merit treatment and follow-up similar to that of AF not related to infection.

Long-term Thromboembolic Risk in Patients With Postoperative Atrial Fibrillation After Left-Sided Heart Valve Surgery.

Importance: New-onset postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery. However, data on the long-term risk of thromboembolism in patients who develop POAF after heart valve surgery are conflicting. In addition, data on stroke prophylaxis in this setting are lacking. Objective: To assess the long-term risk of thromboembolism in patients developing new-onset POAF after isolated left-sided heart valve surgery relative to patients with nonsurgical, nonvalvular atrial fibrillation (NVAF). Design, Setting, and Participants: This observational cohort study was conducted from January 1, 2000, through December 31, 2015, using Danish nationwide registries and the Eastern Danish Heart Surgery Database. Patients who developed POAF after isolated left-sided heart valve surgery (bioprosthetic aortic or mitral valve replacement and/or aortic or mitral valve repair) from 2000 through 2015 were included. These patients were matched with patients with nonsurgical NVAF in a 1:3 ratio by age, sex, heart failure, hypertension, diabetes, a history of thromboembolism, ischemic heart disease, and year of diagnosis. Data analyses took place from January to March 2019. Main Outcomes and Measures: Rates of thromboembolism. Results: Of the 1587 patients who underwent isolated left-sided heart valve surgery, 741 patients (46.7%) developed POAF during admission. Of the 712 patients with POAF who were eligible for matching, 675 patients were matched with 2025 patients with NVAF and made up the study population. In the matched study population, the median age was 71 (interquartile range, 65-77) years, and 1600 (59.3%) were men. Oral anticoagulation therapy was initiated within 30 days postdischarge in 420 patients with POAF (62.9%) and in 1030 patients with NVAF (51.4%). The crude incidence rates of thromboembolism were 21.9 (95% CI, 17.4-27.6) and 17.7 (95% CI, 15.2-20.6) events per 1000 person-years for patients with POAF and patients with NVAF, respectively. In the adjusted analysis, the long-term risk of thromboembolism was similar in patients with POAF and NVAF (hazard ratio, 1.22 [95% CI, 0.88-1.68]). Oral anticoagulation therapy during follow-up was associated with a lower risk of thromboembolic events in patients with POAF (hazard ratio, 0.45 [95% CI, 0.22-0.90]) as well as patients with NVAF (hazard ratio, 0.63 [95% CI, 0.45-0.87]) compared with no anticoagulation therapy. Conclusions and Relevance: New-onset POAF after isolated left-sided heart valve surgery was associated with a similar long-term risk of thromboembolism as NVAF. These data warrant studies addressing the role of anticoagulation therapy in POAF after left-sided heart valve surgery.