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      Muscle mass, muscle strength, and functional capacity in patients with heart failure of Chagas disease and other aetiologies

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          Abstract

          Aims

          Patients with Chagas disease and heart failure (HF) have a poor prognosis similar to that of patients with ischaemic or dilated cardiomyopathy. However, the impact of body composition and muscle strength changes in these aetiologies is still unknown. We aimed to evaluate these parameters across aetiologies in two distinct cohort studies [TESTOsterone‐Heart Failure trial (TESTO‐HF; Brazil) and Studies Investigating Co‐morbidities Aggravating Heart Failure (SICA‐HF; Germany)].

          Methods and results

          A total of 64 male patients with left ventricular ejection fraction ≤40% were matched for body mass index and New York Heart Association class, including 22 patients with Chagas disease (TESTO‐HF; Brazil), and 20 patients with dilated cardiomyopathy and 22 patients with ischaemic heart disease (SICA‐HF; Germany). Lean body mass (LBM), appendicular lean mass (ALM), and fat mass were assessed by dual energy X‐ray absorptiometry. Sarcopenia was defined as ALM divided by height in metres squared <7.0 kg/m 2 (ALM/height 2) and handgrip strength cut‐off for men according to the European Working Group on Sarcopenia in Older People. All patients performed maximal cardiopulmonary exercise testing. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Chagasic and ischaemic patients had lower total fat mass (16.3 ± 8.1 vs. 19.3 ± 8.0 vs. 27.6 ± 9.4 kg; P < 0.05) and reduced peak oxygen consumption (VO 2) (1.17 ± 0.36 vs. 1.15 ± 0.36 vs. 1.50 ± 0.45 L/min; P < 0.05) than patients with dilated cardiomyopathy, respectively. Chagasic patients showed a trend towards decreased LBM when compared with ischaemic patients (48.3 ± 7.6 vs. 54.2 ± 6.3 kg; P = 0.09). Chagasic patients showed lower handgrip strength (27 ± 8 vs. 37 ± 11 vs. 36 ± 14 kg; P < 0.05) and FBF (1.84 ± 0.54 vs. 2.75 ± 0.76 vs. 3.42 ± 1.21 mL/min/100 mL; P < 0.01) than ischaemic and dilated cardiomyopathy patients, respectively. There was no statistical difference in the distribution of sarcopenia between groups ( P = 0.87). In addition, FBF correlated positively with LBM ( r = 0.31; P = 0.012), ALM ( r = 0.25; P = 0.046), and handgrip strength ( r = 0.36; P = 0.004). In a logistic regression model using peak VO 2 as the dependent variable, haemoglobin (odds ratio, 1.506; 95% confidence interval, 1.043–2.177; P = 0.029) and ALM (odds ratio, 1.179; 95% confidence interval, 1.011–1.374; P = 0.035) were independent predictors for peak VO 2 adjusted by age, left ventricular ejection fraction, New York Heart Association, creatinine, and FBF.

          Conclusions

          Patients with Chagas disease and HF have decreased fat mass and exhibit reduced peripheral blood flow and impaired muscle strength compared with ischaemic HF patients. In addition, patients with Chagas disease and HF show a tendency to have greater reduction in total LBM, with ALM remaining an independent predictor of reduced functional capacity in these patients. The percentage of patients affected by sarcopenia was equal between groups.

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          Most cited references35

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          Tolerance and safety of nifurtimox in patients with chronic chagas disease.

          Nifurtimox has been used to treat Chagas disease for 40 years, but tolerance and safety data in adults are scarce. We aimed to evaluate nifurtimox tolerance and safety in a cohort of Trypanosoma cruzi-infected adult patients in a country of nonendemicity. This observational study included all consecutive adults patients who were given a diagnosis of T. cruzi infection from June through December 2008. Eligible patients received nifurtimox at 10 mg/kg/day for 60 days, with regular medical and biological follow-up. Adverse events (AEs) were recorded according to Common Terminology Criteria for Adverse Events, version 3.0. Eighty-one patients received nifurtimox. Eight were lost to follow-up during treatment, and 41 (56.2%) completed the 60-day course. All premature treatment terminations were caused by AEs; 97.5% of patients suffered from AEs, mostly expected (90.5%) and not severe. Gastrointestinal symptoms predominated. Six (7.4%) patients presented with a suspected unexpected serious adverse reaction: drug reaction with eosinophilia and systemic symptoms (n = 3), Quincke edema (n = 1), acute myocarditis (n = 1), and anaphylaxis (n = 1). Patients with 3 or more AEs had an increased risk of premature treatment termination (hazard ratio, 8.42; 95% confidence interval, 1.6-45.5). Nifurtimox is poorly tolerated among adults with chronic Chagas disease, resulting in a low treatment completion rate. Considering the significant risk of serious AEs, close monitoring is required, which may be difficult to implement in poor rural areas of countries of endemicity. The safety and efficacy of nifurtimox and benznidazole should be compared to improve current therapeutic recommendations, and pharmacovigilance systems should be enhanced.
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            Reduced handgrip strength as a marker of frailty predicts clinical outcomes in patients with heart failure undergoing ventricular assist device placement.

            Heart failure (HF) is associated with the derangement of muscle structure and metabolism, contributing to exercise intolerance, frailty, and mortality. Reduced handgrip strength is associated with increased patient frailty and higher morbidity and mortality. We evaluated handgrip strength as a marker of muscle function and frailty for prediction of clinical outcomes after ventricular assist device (VAD) implantation in patients with advanced HF.
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              Three cachexia phenotypes and the impact of fat‐only loss on survival in FOLFIRINOX therapy for pancreatic cancer

              Abstract Background By the traditional definition of unintended weight loss, cachexia develops in ~80% of patients with pancreatic ductal adenocarcinoma (PDAC). Here, we measure the longitudinal body composition changes in patients with advanced PDAC undergoing 5‐fluorouracil, leucovorin, irinotecan, and oxaliplatin therapy. Methods We performed a retrospective review of 53 patients with advanced PDAC on 5‐fluorouracil, leucovorin, irinotecan, and oxaliplatin as first line therapy at Indiana University Hospital from July 2010 to August 2015. Demographic, clinical, and survival data were collected. Body composition measurement by computed tomography (CT), trend, univariate, and multivariate analysis were performed. Results Among all patients, three cachexia phenotypes were identified. The majority of patients, 64%, had Muscle and Fat Wasting (MFW), while 17% had Fat‐Only Wasting (FW) and 19% had No Wasting (NW). NW had significantly improved overall median survival (OMS) of 22.6 months vs. 13.0 months for FW and 12.2 months for MFW (P = 0.02). FW (HR = 5.2; 95% confidence interval = 1.5–17.3) and MFW (HR = 1.8; 95% confidence interval = 1.1–2.9) were associated with an increased risk of mortality compared with NW. OMS and risk of mortality did not differ between FW and MFW. Progression of disease, sarcopenic obesity at diagnosis, and primary tail tumours were also associated with decreased OMS. On multivariate analysis, cachexia phenotype and chemotherapy response were independently associated with survival. Notably, CT‐based body composition analysis detected tissue loss of >5% in 81% of patients, while the traditional definition of >5% body weight loss identified 56.6%. Conclusions Distinct cachexia phenotypes were observed in this homogeneous population of patients with equivalent stage, diagnosis, and first‐line treatment. This suggests cellular, molecular, or genetic heterogeneity of host or tumour. Survival among patients with FW was as poor as for MFW, indicating adipose tissue plays a crucial role in cachexia and PDAC mortality. Adipose tissue should be studied for its mechanistic contributions to cachexia.
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                Author and article information

                Contributors
                stephan.von.haehling@web.de
                Journal
                ESC Heart Fail
                ESC Heart Fail
                10.1002/(ISSN)2055-5822
                EHF2
                ESC Heart Failure
                John Wiley and Sons Inc. (Hoboken )
                2055-5822
                28 August 2020
                October 2020
                : 7
                : 5 ( doiID: 10.1002/ehf2.v7.5 )
                : 3086-3094
                Affiliations
                [ 1 ] Heart Institute (InCor) University of São Paulo Medical School São Paulo Brazil
                [ 2 ] Department of Cardiology and Pneumology University of Göttingen Medical Center (UMG) Robert‐Koch‐Strasse 40 Göttingen D ‐ 37075 Germany
                [ 3 ] German Centre for Cardiovascular Research (DZHK) partner site Göttingen Göttingen Germany
                [ 4 ] Bone Metabolism Laboratory, Rheumatology Division University of São Paulo Medical School São Paulo Brazil
                [ 5 ] Department of Cardiology (CVK) and Berlin Institute of Health Center for Regenerative Therapies (BCRT) Charité ‐ Universitätsmedizin Berlin Berlin Germany
                [ 6 ] German Centre for Cardiovascular Research (DZHK) partner site Berlin Charité ‐ Universitätsmedizin Berlin Berlin Germany
                [ 7 ] School of Physical Education and Sports University of São Paulo São Paulo Brazil
                Author notes
                [*] [* ] Correspondence to: Prof. Stephan von Haehling, MD PhD FESC FHFA, Department of Cardiology and Pneumology, University of Göttingen Medical Center (UMG), Robert‐Koch‐Strasse 40, D ‐ 37075 Göttingen, Germany. Tel: +49 551 39 20911; Fax: +49 551 39 20918. Email: stephan.von.haehling@ 123456web.de

                Author information
                https://orcid.org/0000-0001-6477-8741
                Article
                EHF212936 ESCHF-20-00554
                10.1002/ehf2.12936
                7524247
                32860353
                8dbafa4e-dbc2-4b5f-b27d-78930e5bf7ef
                © 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/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 17 June 2020
                : 14 July 2020
                : 18 July 2020
                Page count
                Figures: 2, Tables: 3, Pages: 9, Words: 4219
                Funding
                Funded by: Boehringer Ingelheim and Amgen
                Funded by: Innovative Medicines Initiative , open-funder-registry 10.13039/501100010767;
                Award ID: 115621
                Funded by: German Center for Cardiovascular Research (DZHK)
                Funded by: Fundação de Amparo à Pesquisa do Estado de São Paulo , open-funder-registry 10.13039/501100001807;
                Award ID: 2016/24306‐0
                Award ID: 2015/22814‐5
                Funded by: Conselho Nacional de Desenvolvimento Científico e Tecnológico , open-funder-registry 10.13039/501100003593;
                Award ID: 148758/2016‐9
                Award ID: 303573/2015‐5
                Funded by: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior , open-funder-registry 10.13039/501100002322;
                Award ID: 001
                Categories
                Original Research Article
                Original Research Articles
                Custom metadata
                2.0
                October 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.1 mode:remove_FC converted:29.09.2020

                chagas disease,heart failure,body composition changes,muscle strength

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