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      Effectiveness of sacubitril–valsartan in cancer patients with heart failure

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          Abstract

          Aims

          Current guidelines recommend sacubitril/valsartan for patients with heart failure and reduced left ventricular ejection fraction (LVEF), but there is lack of evidence of its efficacy and safety in cancer therapy‐related cardiac dysfunction (CTRCD). Our aim was to analyse the potential benefit of sacubitril/valsartan in patients with CTRCD.

          Methods and results

          We performed a retrospective multicentre registry (HF‐COH) in six Spanish hospitals with cardio‐oncology clinics including all patients treated with sacubitril/valsartan. Demographic and clinical characteristics and laboratory and echocardiographic data were collected. Median follow‐up was 4.6 [1; 11] months. Sixty‐seven patients were included (median age was 63 ± 14 years; 64% were female, 87% had at least one cardiovascular risk factor). Median time from anti‐cancer therapy to CTRD was 41 [10; 141] months. Breast cancer (45%) and lymphoma (39%) were the most frequent neoplasm, 31% had metastatic disease, and all patients were treated with combination antitumor therapy (70% with anthracyclines). Thirty‐nine per cent of patients had received thoracic radiotherapy. Baseline median LVEF was 33 [27; 37], and 21% had atrial fibrillation. Eighty‐five per cent were on beta‐blocker therapy and 76% on mineralocorticoid receptor antagonists; 90% of the patients were symptomatic NYHA functional class ≥II. Maximal sacubitril/valsartan titration dose was achieved in 8% of patients (50 mg b.i.d.: 60%; 100 mg b.i.d.: 32%). Sacubitril/valsartan was discontinued in four patients (6%). Baseline N‐terminal pro‐B‐type natriuretic peptide levels (1552 pg/mL [692; 3624] vs. 776 [339; 1458]), functional class (2.2 ± 0.6 vs. 1.6 ± 0.6), and LVEF (33% [27; 37] vs. 42 [35; 50]) improved at the end of follow‐up (all P values ≤0.01). No significant statistical differences were found in creatinine (0.9 mg/dL [0.7; 1.1] vs. 0.9 [0.7; 1.1]; P = 0.055) or potassium serum levels (4.5 mg/dL [4.1; 4.8] vs. 4.5 [4.2; 4.8]; P = 0.5). Clinical, echocardiographic, and biochemical improvements were found regardless of the achieved sacubitril–valsartan dose (low or medium/high doses).

          Conclusions

          Our experience suggests that sacubitril/valsartan is well tolerated and improves echocardiographic functional and structural parameters, N‐terminal pro‐B‐type natriuretic peptide levels, and symptomatic status in patients with CTRCD.

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          Most cited references4

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          Clinical practice update on heart failure 2019: pharmacotherapy, procedures, devices and patient management. An expert consensus meeting report of The Heart Failure Association of the European Society of Cardiology

          The European Society of Cardiology (ESC) has published a series of guidelines on heart failure (HF) over the last 25 years, most recently in 2016. Given the amount of new information that has become available since then, the Heart Failure Association (HFA) of the ESC recognized the need to review and summarise recent developments in a consensus document. Here we report from the HFA workshop that was held in January 2019 in Frankfurt, Germany. This expert consensus report is neither a guideline update nor a position statement, but rather a summary and consensus view in the form of consensus recommendations. The report describes how these guidance statements are supported by evidence, it makes some practical comments, and it highlights new research areas and how progress might change the clinical management of HF. We have avoided re-interpretation of information already considered in the 2016 ESC/HFA guidelines. Specific new recommendations have been made based on the evidence from major trials published since 2016, including sodium-glucose co-transporter 2 inhibitors in type 2 diabetes mellitus, MitraClip for functional mitral regurgitation, atrial fibrillation ablation in HF, tafamidis in cardiac transthyretin amyloidosis, rivaroxaban in HF, implantable cardioverter-defibrillators in non-ischaemic HF, and telemedicine for HF. In addition, new trial evidence from smaller trials and updated meta-analyses have given us the chance to provide refined recommendations in selected other areas. Further, new trial evidence is due in many of these areas and others over the next 2 years, in time for the planned 2021 ESC guidelines on the diagnosis and treatment of acute and chronic heart failure.
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            Cardio-Oncology Services: rationale, organization, and implementation

            Anticancer therapies have extended the lives of millions of patients with malignancies, but for some this benefit is tempered by adverse cardiovascular (CV) effects. Cardiotoxicity may occur early or late after treatment initiation or termination. The extent of this cardiotoxicity is variable, depending on the type of drug used, combination with other drugs, mediastinal radiotherapy, the presence of CV risk factors, and comorbidities. A recent position paper from the European Society of Cardiology addressed the management of CV monitoring and management of patients treated for cancer.
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              Cardio-Onco-Hematology in Clinical Practice. Position Paper and Recommendations.

              Improvements in early detection and treatment have markedly reduced cancer-related mortality. However survival not only depends on effectively cure cancer, but prevention, diagnosis and treatment of cancer-related complications is also needed. Cardiovascular toxicity is a widespread problem across many classes of therapeutic schemes, however scientific evidence in the management of cardiovascular complications of onco-hematological patients is scarce, as these patients have been systematically excluded from clinical trials and current recommendations are based on expert consensus. Multidisciplinary teams are mandatory to decrease morbidity and mortality from both cardiotoxicity and cancer itself. An excessive concern for the occurrence of cardiovascular toxicity, can avoid potentially curative therapies, while underestimating this risk, increases long-term mortality of cancer survivors. The objective of this consensus document, developed in collaboration of the Spanish Society of Cardiology, the Spanish Society of Medical Oncology, the Spanish Society of Radiation Oncology and the Spanish Society of Hematology, is to update the necessary concepts and expertise on cardio-onco-hematology that enable its application in daily clinical practice and to promote the development of local multidisciplinary teams, to improve the cardiovascular health of patients with cancer.
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                Author and article information

                Contributors
                anamartin.amg@gmail.com
                Journal
                ESC Heart Fail
                ESC Heart Fail
                10.1002/(ISSN)2055-5822
                EHF2
                ESC Heart Failure
                John Wiley and Sons Inc. (Hoboken )
                2055-5822
                05 February 2020
                April 2020
                : 7
                : 2 ( doiID: 10.1002/ehf2.v7.2 )
                : 763-767
                Affiliations
                [ 1 ] Department of Cardiology Hospital Universitario de Salamanca—IBSAL, University of Salamanca Paseo de San Vicente 58‐187 37007 Salamanca Spain
                [ 2 ] CIBERCV Instituto de Salud Carlos III Madrid Spain
                [ 3 ] Department of Cardiology Hospital La Paz—IdiPAZ Madrid Spain
                [ 4 ] Department of Cardiology Hospital Puerta de Hierro—IDIPHISA, Majadahonda Madrid Spain
                [ 5 ] Department of Cardiology Hospital Virgen de la Macarena—IBiS Seville Spain
                [ 6 ] Department of Cardiology Hospital Universitari Germans Trias I Pujol—IGTP, Badalona Barcelona Spain
                [ 7 ] Department of Cardiology Hospital Clínico Universitario de Santiago de Compostela—IDIS Santiago de Compostela, A Coruña Spain
                Author notes
                [*] [* ] Correspondence to: Ana Martín‐Garcia, Department of Cardiology, Hospital Universitario de Salamanca—IBSAL, University of Salamanca, Paseo de San Vicente 58‐187, 37007 Salamanca, Spain. Tel: 34‐923291100 (ext 55356). Email: anamartin.amg@ 123456gmail.com

                [†]

                Authors have contributed equally and should be considered co‐first authors.

                Article
                EHF212627 ESCHF-19-00269
                10.1002/ehf2.12627
                7160493
                32022485
                629a784a-624f-4217-acc7-a4f394374240
                © 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 29 August 2019
                : 01 December 2019
                : 03 January 2020
                Page count
                Figures: 1, Tables: 3, Pages: 5, Words: 1719
                Funding
                Funded by: Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades, Spain
                Award ID: PIE14/00066
                Funded by: EU–European Regional Development Fund , open-funder-registry 10.13039/501100008530;
                Award ID: PIE14/00066
                Funded by: Spanish Cardiovascular Network (CIBERCV)
                Award ID: PIE14/00066
                Categories
                Short Communication
                Short Communications
                Custom metadata
                2.0
                April 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.0 mode:remove_FC converted:16.04.2020

                cancer,cardio‐oncology,cardiotoxicity,heart failure,sacubitril–valsartan

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