Publications by authors named "Stephan von Haehling"

390 Publications

Critical appraisal of the 2020 ESC guideline recommendations on diagnosis and risk assessment in patients with suspected non-ST-segment elevation acute coronary syndrome.

Clin Res Cardiol 2021 Feb 26. Epub 2021 Feb 26.

3rd Department of Internal Medicine, Cardiology and Intensive Care Medicine, Wilhelminenhospital, Vienna, Austria.

Multiple new recommendations have been introduced in the 2020 ESC guidelines for the management of acute coronary syndromes with a focus on diagnosis, prognosis, and management of patients presenting without persistent ST-segment elevation. Most recommendations are supported by high-quality scientific evidence. The guidelines provide solutions to overcome obstacles presumed to complicate a convenient interpretation of troponin results such as age-, or sex-specific cutoffs, and to give practical advice to overcome delays of laboratory reporting. However, in some areas, scientific support is less well documented or even missing, and other areas are covered rather by expert opinion or subjective recommendations. We aim to provide a critical appraisal on several recommendations, mainly related to the diagnostic and prognostic assessment, highlighting the discrepancies between Guideline recommendations and the existing scientific evidence.
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http://dx.doi.org/10.1007/s00392-021-01821-2DOI Listing
February 2021

Ferric carboxymaltose for the treatment of iron-deficient heart failure patients: a systematic review and meta-analysis.

ESC Heart Fail 2020 Dec;7(6):3392-3400

Monash University, Australia.

Aims: Intravenous ferric carboxymaltose (FCM) has been shown to improve functional capacity and quality of life in iron deficient heart failure patients. However, FCM's effect on hospitalizations and mortality remains unclear as previous randomized controlled trials (RCTs) and their meta-analyses have been underpowered to detect significant differences. We sought to conduct an updated meta-analysis using recently published RCT data.

Methods And Results: Online databases were searched from inception until November 2020 for RCTs evaluating the effects of FCM on clinical outcomes in iron-deficient heart failure patients. Outcomes of interest included heart failure hospitalizations, all-cause mortality, and cardiovascular mortality. Meta-analysis was performed using a fixed-effect model and estimates were reported as odds ratios (ORs), hazard ratios, or rate ratios (RRs) along with corresponding 95% confidence intervals (CIs). A total of 1947 patients (n = 1062 in the FCM group; n = 885 in the placebo group) were included. FCM, compared with placebo, significantly reduced the risk of the composite endpoint of time to first heart failure hospitalization or cardiovascular death (hazard ratio = 0.76; 95% CI = 0.63-0.90; I = 55%). FCM also significantly reduced the risk of recurrent heart failure hospitalizations (RR = 0.68; 95% CI = 0.54-0.85; I = 71%) and recurrent cardiovascular hospitalizations (RR = 0.71; 95% CI = 0.59-0.86; I = 56%). However, FCM had no significant effect on the risk of all-cause (OR = 0.97; 95% CI = 0.73-1.28; I = 0%) or cardiovascular mortality (OR = 0.93; 95% CI = 0.69-1.27; I = 0%).

Conclusions: Ferric carboxymaltose reduces heart failure hospitalizations and cardiovascular hospitalizations with no beneficial effect on all-cause and cardiovascular mortality in iron-deficient heart failure patients. These findings reinforce the role of FCM as a therapeutic option in heart failure patients.
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http://dx.doi.org/10.1002/ehf2.13146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754952PMC
December 2020

Effects of statins on mitochondrial pathways.

J Cachexia Sarcopenia Muscle 2021 Jan 29. Epub 2021 Jan 29.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Statins are a family of drugs that are used for treating hyperlipidaemia with a recognized capacity to prevent cardiovascular disease events. They inhibit β-hydroxy β-methylglutaryl-coenzyme A reductase, i.e. the rate-limiting enzyme in mevalonate pathway, reduce endogenous cholesterol synthesis, and increase low-density lipoprotein clearance by promoting low-density lipoprotein receptor expression mainly in the hepatocytes. Statins have pleiotropic effects including stabilization of atherosclerotic plaques, immunomodulation, anti-inflammatory properties, improvement of endothelial function, antioxidant, and anti-thrombotic action. Despite all beneficial effects, statins may elicit adverse reactions such as myopathy. Studies have shown that mitochondria play an important role in statin-induced myopathies. In this review, we aim to report the mechanisms of action of statins on mitochondrial function. Results have shown that statins have several effects on mitochondria including reduction of coenzyme Q10 level, inhibition of respiratory chain complexes, induction of mitochondrial apoptosis, dysregulation of Ca metabolism, and carnitine palmitoyltransferase-2 expression. The use of statins has been associated with the onset of additional pathological conditions like diabetes and dementia as a result of interference with mitochondrial pathways by various mechanisms, such as reduction in mitochondrial oxidative phosphorylation, increase in oxidative stress, decrease in uncoupling protein 3 concentration, and interference in amyloid-β metabolism. Overall, data reported in this review suggest that statins may have major effects on mitochondrial function, and some of their adverse effects might be mediated through mitochondrial pathways.
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http://dx.doi.org/10.1002/jcsm.12654DOI Listing
January 2021

An overview of anamorelin as a treatment option for cancer-associated anorexia and cachexia.

Expert Opin Pharmacother 2021 Jan 25:1-8. Epub 2021 Jan 25.

Department of Cardiology and Pneumology, University of Göttingen Medical Center (UMG), Göttingen, Germany;s German Centre for Cardiovascular Research (DZHK) Partner Site Göttingen , Göttingen, Germany.

Introduction: Cancer cachexia is a complex multifaceted syndrome involving functional impairment, changes in body composition, and nutritional disorders. The treatment of cancer cachexia can be based on these three domains of the syndrome. Phase II and III trials of anamorelin, a ghrelin mimetic agent, have been shown to increase body weight in patients with cancer cachexia, mainly by increasing muscle and fat mass. Anamorelin has been shown to improve anorexia scores.

Areas Covered: This review aims to outline the effect of anamorelin on body composition and functional parameters as well as to discuss the clinical importance of these alterations in patients with cancer cachexia.

Expert Opinion: To date, there is no treatment approved to enhance body composition and functional parameters in patients with cancer cachexia. Anamorelin, the most advanced therapy to treat cachexia, has not yielded convincing results in all aspects of the syndrome. In particular, no effect has been noted on physical function and long-term survival. Along with these essential improvements for future interventions with anamorelin, subsequent studies must address other etiologies of cancer, rather than non-small cell lung cancer, and add complementary therapies, such as exercise training and nutritional interventions, in an attempt to overcome cancer cachexia.
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http://dx.doi.org/10.1080/14656566.2021.1873954DOI Listing
January 2021

Heart failure with preserved ejection fraction in coronavirus disease 2019 patients: the promising role of diuretic therapy in critically ill patients.

ESC Heart Fail 2021 Jan 14. Epub 2021 Jan 14.

Department of Cardiology and Pneumology, Heart Center, University of Göttingen Medical Center, Göttingen, Germany.

The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on diastolic function is less known. We describe a 46-year-old man with a history of mild hypertension who presented to the emergency department with fever, cough, and myalgia for 2 days. The patient was tested positive for SARS-CoV-2. He was admitted and started on a combination of antiviral and antimicrobial therapy. He developed respiratory distress 2 days later, and O saturation declined. Blood tests showed an increased N-terminal pro-B type natriuretic peptide (NT-proBNP) level, and echocardiography showed normal left ventricular ejection fraction and E/e' ratio of 16. Computed tomography scan showed interstitial pulmonary oedema and prominent peripheral pulmonary vascular markings. Given these findings, heart failure with preserved ejection fraction (HFpEF) was considered. Low-dose diuretic was started, and fluid administration was restricted, resulting in a decrease in NT-proBNP level, clinical and haemodynamic stabilization, and improved oxygenation. This case highlights the occurrence of HFpEF in coronavirus disease 2019.
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http://dx.doi.org/10.1002/ehf2.13175DOI Listing
January 2021

Weight loss, malnutrition, and cachexia in COVID-19: facts and numbers.

J Cachexia Sarcopenia Muscle 2021 02 31;12(1):9-13. Epub 2020 Dec 31.

Berlin Institute of Health Center for Regenerative Therapies (BCRT), Berlin, Germany.

Patients with COVID-19 disease are prone to develop significant weight loss and clinical cachexia. Three reports with altogether 589 patients that reported on weight loss and cachexia in COVID-19 were identified. Disease severity of patients and the timing of the assessment during the disease course in these patients were variable-65 patients (11%) were intensive care treated at the time of assessment, and 183 (31%) were cared for in sub-intensive or intermediate care structures. The frequency of weight loss ≥5% (that defines cachexia) was 37% (range 29-52%). Correlates of weight loss occurrence were reported to be raised C-reactive protein levels, impaired renal function status, and longer duration of COVID-19 disease. Underweight status by WHO criteria (BMI < 18.5 kg/m ) was only observed in 4% of patients analysing data from seven studies with 6661 patients. Cachexia assessment in COVID-19 needs assessment of weight loss. COVID-19 associated cachexia is understood to affect muscle and fat tissue as is also seen in many other chronic illness-associated forms of cachexia. There are many factors that can contribute to body wasting in COVID-19, and they include loss of appetite and taste, fever and inflammation, immobilization, as well as general malnutrition, catabolic-anabolic imbalance, endocrine dysfunction, and organ-specific complications of COVID-19 disease such as cardiac and renal dysfunction. Treatment of COVID-19 patients should include a focus on nutritional support and rehabilitative exercise whenever possible. Specific anti-cachectic therapies for COVID-19 do not exist, but constitute a high medical need to prevent long-term disability due to acute COVID-19 disease.
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http://dx.doi.org/10.1002/jcsm.12674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890265PMC
February 2021

Nutrition in the spotlight in cachexia, sarcopenia and muscle: avoiding the wildfire.

J Cachexia Sarcopenia Muscle 2021 Feb 31;12(1):3-8. Epub 2020 Dec 31.

Department of Cardiology and Pneumology, University Medicine Goettingen, Goettingen, Germany.

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http://dx.doi.org/10.1002/jcsm.12673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890147PMC
February 2021

The 10th year of the Journal of Cachexia, Sarcopenia and Muscle.

J Cachexia Sarcopenia Muscle 2020 12;11(6):1390-1395

Department of Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany.

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http://dx.doi.org/10.1002/jcsm.12657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749579PMC
December 2020

Blocking myostatin: muscle mass equals muscle strength?

J Cachexia Sarcopenia Muscle 2020 12;11(6):1396-1398

Berlin Institute of Health Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Berlin, Germany.

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http://dx.doi.org/10.1002/jcsm.12647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749583PMC
December 2020

Mortality and morbidity 1 year after stopping a remote patient management intervention: extended follow-up results from the telemedical interventional management in patients with heart failure II (TIM-HF2) randomised trial.

Lancet Digit Health 2020 01 12;2(1):e16-e24. Epub 2019 Dec 12.

Department of Cardiology, Berlin Institute of Health Center for Regenerative Therapies, German Centre for Cardiovascular Research Partner Site Berlin, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Background: The Telemedical Interventional Management in Heart Failure II (TIM-HF2) trial showed that, compared with usual care, a structured remote patient management (RPM) intervention done over 12-months reduced the percentage of days lost due to unplanned cardiovascular hospitalisations and all-cause death. The aim of the study was to evaluate whether this clinical benefit seen for the RPM group during the initial 12 month follow-up of the TIM-HF2 trial would be sustained 1 year after stopping the RPM intervention.

Methods: TIM-HF2 was a prospective, randomised, multicentre trial done in 43 hospitals, 60 cardiology practices, and 87 general practitioners in Germany. Patients with heart failure, New York Heart Association functional class II or III, and who had been hospitalised for heart failure within 12 months before randomisation were randomly assigned to either the RPM intervention or usual care. At the final study visit (main trial), the RPM intervention was stopped and the 1 year extended follow-up period started, which lasted 1 year. The primary outcome was percentage of days lost due to unplanned cardiovascular hospitalisations and all-cause mortality. Analyses were done using the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, number NCT01878630.

Findings: Between Aug 13, 2013, and May 12, 2017, 1538 patients were enrolled (765 to the remote patient management group and 773 to the usual care group) in the main trial. 671 of 765 patients in the remote patient management group and 673 of 773 in the usual care group completed the main trial and started the extended follow-up period up to 1 year later. In the extended follow-up period, the percentage of days lost due to unplanned cardiovascular hospital admissions and all-cause mortality did not differ significantly between groups weighted mean 5·95% [95% CI 4·59-7·31] in the RPM group vs 6·64% [95% CI 5·19-8·08] in the usual care group [rate ratio 0·79; 95% CI 0·78-1·21]). However, when data from the main trial and the extended follow-up period were combined, the percentage of days lost due to unplanned cardiovascular hospitalisation or all-cause death was significantly less in patients allocated to the RPM group (382 [50%] of 765; weighted mean 9·28%; 95% CI 7·76-10·81) than in the UC group (398 [51%] of 773; 11·78%; 95% CI 10·08-13·49; ratio of weighted average 0·79; 95% CI 0·62-1·00; p=0·0486).

Interpretation: The positive effect of our RPM intervention on morbidity and mortality over the course of the main trial was no longer observed 1 year after stopping the RPM intervention. However, because the TIM-HF2 trial was not powered to show significance during the extended follow-up period, our results are exploratory and require further research.

Funding: German Federal Ministry of Education and Research.
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http://dx.doi.org/10.1016/S2589-7500(19)30195-5DOI Listing
January 2020

Heart failure in the last year: progress and perspective.

ESC Heart Fail 2020 Dec 5. Epub 2020 Dec 5.

Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy.

Research about heart failure (HF) has made major progress in the last years. We give here an update on the most recent findings. Landmark trials have established new treatments for HF with reduced ejection fraction. Sacubitril/valsartan was superior to enalapril in PARADIGM-HF trial, and its initiation during hospitalization for acute HF or early after discharge can now be considered. More recently, new therapeutic pathways have been developed. In the DAPA-HF and EMPEROR-Reduced trials, dapagliflozin and empagliflozin reduced the risk of the primary composite endpoint, compared with placebo [hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.65-0.85; P < 0.001 and HR 0.75; 95% CI 0.65-0.86; P < 0.001, respectively]. Second, vericiguat, an oral soluble guanylate cyclase stimulator, reduced the composite endpoint of cardiovascular death or HF hospitalization vs. placebo (HR 0.90; 95% CI 0.82-0.98; P = 0.02). On the other hand, both the diagnosis and treatment of HF with preserved ejection fraction, as well as management of advanced HF and acute HF, remain challenging. A better phenotyping of patients with HF would be helpful for prognostic stratification and treatment selection. Further aspects, such as the use of devices, treatment of arrhythmias, and percutaneous treatment of valvular heart disease in patients with HF, are also discussed and reviewed in this article.
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http://dx.doi.org/10.1002/ehf2.13124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754751PMC
December 2020

Ventricular tachycardia, premature ventricular contractions, and mortality in unselected patients with lung, colon, or pancreatic cancer: a prospective study.

Eur J Heart Fail 2020 Nov 22. Epub 2020 Nov 22.

Division of Cardiology and Metabolism, Department of Cardiology (CVK), Charité University Medicine Berlin, Berlin, Germany.

Aims: Many cancer patients die due to cardiovascular disease and sudden death, but data on ventricular arrhythmia prevalence and prognostic importance are not known.

Methods And Results: Between 2005 and 2010, we prospectively enrolled 120 unselected patients with lung, colon, or pancreatic cancer due to one of three diagnoses: colorectal (n=33), pancreatic (n=54), or non-small cell lung cancer (n=33). All were free of manifest cardiovascular disease. They were compared to 43 healthy controls similar in age and sex distribution. Each participant underwent 24-hour electrocardiogram recording and cancer patients were followed for up to 12.5 years for survival (median 21 months). 96 cancer patients (80%) died during follow-up (5-year survival: 27% [95%CI 19-35%]). Non-sustained ventricular tachycardia (NSVT) was more frequent in cancer patients vs. controls (8% vs. 0%, p=0.021). The number of premature ventricular contractions (PVCs) over 24 hours was not increased in cancer patients vs. controls (median 4 vs. 9, p=0.2). In multivariable analysis, NSVT (HR 2.44, p=0.047) and PVCs (per 100, HR 1.021, p=0.047) were both significant predictors of mortality, independent of other univariable mortality predictors including tumour stage, cancer type, potassium concentration, prior surgery, prior cardiotoxic chemotherapy, and haemoglobin. In patients with colorectal and pancreatic cancer, ≥50 PVCs/24 hours predicted mortality (HR 2.30, p=0.0024), and was identified in 18% and 26% of patients, respectively.

Conclusions: Non-sustained ventricular tachycardia is more frequent in unselected patients with colorectal, pancreatic, and non-small cell lung cancer and together with PVCs predict long-term mortality. This raises the prospect of cardiovascular mortality being a target for future treatment interventions in selected cancers.
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http://dx.doi.org/10.1002/ejhf.2059DOI Listing
November 2020

Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial.

Lancet 2020 12 13;396(10266):1895-1904. Epub 2020 Nov 13.

Department of Heart Diseases, Wrocław Medical University, Wroclaw, Poland; Center for Heart Diseases, University Hospital in Wrocław, Wroclaw, Poland.

Background: Intravenous ferric carboxymaltose has been shown to improve symptoms and quality of life in patients with chronic heart failure and iron deficiency. We aimed to evaluate the effect of ferric carboxymaltose, compared with placebo, on outcomes in patients who were stabilised after an episode of acute heart failure.

Methods: AFFIRM-AHF was a multicentre, double-blind, randomised trial done at 121 sites in Europe, South America, and Singapore. Eligible patients were aged 18 years or older, were hospitalised for acute heart failure with concomitant iron deficiency (defined as ferritin <100 μg/L, or 100-299 μg/L with transferrin saturation <20%), and had a left ventricular ejection fraction of less than 50%. Before hospital discharge, participants were randomly assigned (1:1) to receive intravenous ferric carboxymaltose or placebo for up to 24 weeks, dosed according to the extent of iron deficiency. To maintain masking of patients and study personnel, treatments were administered in black syringes by personnel not involved in any study assessments. The primary outcome was a composite of total hospitalisations for heart failure and cardiovascular death up to 52 weeks after randomisation, analysed in all patients who received at least one dose of study treatment and had at least one post-randomisation data point. Secondary outcomes were the composite of total cardiovascular hospitalisations and cardiovascular death; cardiovascular death; total heart failure hospitalisations; time to first heart failure hospitalisation or cardiovascular death; and days lost due to heart failure hospitalisations or cardiovascular death, all evaluated up to 52 weeks after randomisation. Safety was assessed in all patients for whom study treatment was started. A pre-COVID-19 sensitivity analysis on the primary and secondary outcomes was prespecified. This study is registered with ClinicalTrials.gov, NCT02937454, and has now been completed.

Findings: Between March 21, 2017, and July 30, 2019, 1525 patients were screened, of whom 1132 patients were randomly assigned to study groups. Study treatment was started in 1110 patients, and 1108 (558 in the carboxymaltose group and 550 in the placebo group) had at least one post-randomisation value. 293 primary events (57·2 per 100 patient-years) occurred in the ferric carboxymaltose group and 372 (72·5 per 100 patient-years) occurred in the placebo group (rate ratio [RR] 0·79, 95% CI 0·62-1·01, p=0·059). 370 total cardiovascular hospitalisations and cardiovascular deaths occurred in the ferric carboxymaltose group and 451 occurred in the placebo group (RR 0·80, 95% CI 0·64-1·00, p=0·050). There was no difference in cardiovascular death between the two groups (77 [14%] of 558 in the ferric carboxymaltose group vs 78 [14%] in the placebo group; hazard ratio [HR] 0·96, 95% CI 0·70-1·32, p=0·81). 217 total heart failure hospitalisations occurred in the ferric carboxymaltose group and 294 occurred in the placebo group (RR 0·74; 95% CI 0·58-0·94, p=0·013). The composite of first heart failure hospitalisation or cardiovascular death occurred in 181 (32%) patients in the ferric carboxymaltose group and 209 (38%) in the placebo group (HR 0·80, 95% CI 0·66-0·98, p=0·030). Fewer days were lost due to heart failure hospitalisations and cardiovascular death for patients assigned to ferric carboxymaltose compared with placebo (369 days per 100 patient-years vs 548 days per 100 patient-years; RR 0·67, 95% CI 0·47-0·97, p=0·035). Serious adverse events occurred in 250 (45%) of 559 patients in the ferric carboxymaltose group and 282 (51%) of 551 patients in the placebo group.

Interpretation: In patients with iron deficiency, a left ventricular ejection fraction of less than 50%, and who were stabilised after an episode of acute heart failure, treatment with ferric carboxymaltose was safe and reduced the risk of heart failure hospitalisations, with no apparent effect on the risk of cardiovascular death.

Funding: Vifor Pharma.
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http://dx.doi.org/10.1016/S0140-6736(20)32339-4DOI Listing
December 2020

Cardiotoxicity and Cardiovascular Biomarkers in Patients With Breast Cancer: Data From the GeparOcto-GBG 84 Trial.

J Am Heart Assoc 2020 12 16;9(23):e018143. Epub 2020 Nov 16.

Department of Cardiology and Pneumology University of Göttingen Medical Center Göttingen Germany.

Background Patients with breast cancer can be affected by cardiotoxic reactions through cancer therapies. Cardiac biomarkers, like NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity cardiac troponin T, might have predictive value. Methods and Results Echocardiography, ECG, hemodynamic parameters, NT-proBNP and high-sensitivity cardiac troponin T were assessed in 853 patients with early-stage breast cancer randomized in the German Breast Group GeparOcto-GBG 84 phase III trial. Patients received neo-adjuvant dose-dense, dose-intensified epirubicin, paclitaxel, and cyclophosphamide (iddEPC group, n=424) or paclitaxel, non-pegylated doxorubicin, and in triple negative breast cancer, (paclitaxel, non-pegylated doxorubicin, carboplatin group, n=429) treatment for 18 weeks. Patients positive for human epidermal growth receptor 2 (n=354, 41.5%) received monoclonal antibodies on top of allocated therapy; 119 (12.9%) of all patients showed a cardiotoxic reaction during therapy (15 [1.8%] using a more strict definition). Presence of cardiotoxic reactions was irrespective of treatment allocation (=0.31). Small but significant increases in NT-proBNP developed early in patients with a cardiotoxic reaction as compared with those without in whom NT-proBNP rose only towards the end of therapy (=0.04). High-sensitivity cardiac troponin T rose early in both groups. Logistic regression showed that NT-proBNP (odds ratio [OR], 1.03; 95% CI, 1.008-1.055; =0.01) and hemoglobin (OR, 1.31; 95% CI, 1.05-1.63; =0.02) measured at 6 weeks after treatment initiation were significantly associated with cardiotoxic reactions. Conclusions NT-proBNP and hemoglobin are significantly associated with cardiotoxic reactions in patients with early-stage breast cancer undergoing dose-dense and dose-intensified chemotherapy, but high-sensitivity cardiac troponin T is not. Registration URL: http://www.clinicaltrials.gov; Unique identifier: NCT02125344.
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http://dx.doi.org/10.1161/JAHA.120.018143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763783PMC
December 2020

Early rehabilitation after stroke: relationship between the heart rate variability and functional outcome.

ESC Heart Fail 2020 10 30;7(5):2983-2991. Epub 2020 Jul 30.

Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Center for Stroke Research Berlin (CSB), Charité Universitätsmedizin Berlin, Berlin, Germany.

Aims: Impaired autonomic nervous system regulation is frequently observed in patients with stroke. The aim of this prospective study was to evaluate the impact of cardiac autonomic tone on functional outcome after the early post-stroke rehabilitation.

Methods And Results: One hundred and three consecutive patients (67 ± 11 years, body mass index (BMI) 27.1 ± 5.4 kg/m , 64% men) with ischaemic (84% of patients) and haemorrhagic stroke were studied. Depressed heart rate variability (HRV), as a surrogate marker of increased sympathetic tone, was defined by the standard deviation of NN intervals < 100 ms and HRV triangular index ≤ 20 assessed from a 24 h Holter electrocardiogram at admission to rehabilitation (23 ± 16 days after stroke). Twenty-two per cent of patients had depressed HRV at baseline and were comparable with patients with normal HRV with regard to their functional [Barthel Index (BI), modified Rankin Scale (mRS), and Rivermead Motor Assessment (RMA)] and biochemical status. After a 4-week follow-up, 70% of patients with depressed HRV showed a cumulative functional disability, defined by mRS ≥ 4, BI ≤ 70, and RMA ≤ 5, in contrast to patients with normal HRV (35%, P = 0.003). Patients with depressed HRV showed a worse functional status by BI (-16%, P < 0.001), RMA (-12%, P < 0.05), and mRS (+16%, P < 0.01), compared with patients with normal HRV. Cumulative functional disability was associated with depressed HRV (odds ratio 4.25, 95% confidence interval 1.56-11.54, P < 0.005) after adjustment for age, sex, and body mass index (odds ratio 4.6, 95% confidence interval 1.42-14.97, P < 0.05).

Conclusions: The presence of autonomic cardiovascular dysregulation in patients with subacute stroke was associated with adverse functional outcome after the early post-stroke rehabilitation.
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http://dx.doi.org/10.1002/ehf2.12917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524118PMC
October 2020

ESC Heart Failure increases its impact factor.

ESC Heart Fail 2020 Oct 28. Epub 2020 Oct 28.

Department of Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany.

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http://dx.doi.org/10.1002/ehf2.13069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755017PMC
October 2020

High soluble transferrin receptor in patients with heart failure: a measure of iron deficiency and a strong predictor of mortality.

Eur J Heart Fail 2020 Oct 27. Epub 2020 Oct 27.

Department of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland.

Aims: Iron deficiency (ID) is frequent in heart failure (HF), linked with exercise intolerance and poor prognosis. Intravenous iron repletion improves clinical status in HF patients with left ventricular ejection fraction (LVEF) ≤45%. However, uncertainty exists about the accuracy of serum biomarkers in diagnosing ID. The aims of this study were (i) to identify the iron biomarker with the greatest accuracy for the diagnosis of ID in bone marrow in patients with ischaemic HF, and (ii) to establish the prevalence of ID using this biomarker and its prognostic value in HF patients.

Methods And Results: Bone marrow was stained for iron in 30 patients with ischaemic HF with LVEF ≤45% and 10 healthy controls, and ID was diagnosed for 0-1 grades (Gale scale). A total of 791 patients with HF with LVEF ≤45% were prospectively followed up for 3 years. Serum ferritin, transferrin saturation, soluble transferrin receptor (sTfR) were assessed as iron biomarkers. Most patients with HF (n = 25, 83%) had ID in bone marrow, but none of the controls (P < 0.001). Serum sTfR had the best accuracy in predicting ID in bone marrow (area under the curve 0.920, 95% confidence interval 0.761-0.987, for cut-off 1.25 mg/L sensitivity 84%, specificity 100%). Serum sTfR was ≥1.25 mg/L in 47% of HF patients, in 56% and 46% of anaemics and non-anaemics, respectively (P < 0.05). The reclassification methods revealed that serum sTfR significantly added the prognostic value to the baseline prognostic model, and to the greater extent than plasma N-terminal pro B-type natriuretic peptide. Based on internal derivation and validation procedures, serum sTfR ≥1.41 mg/L was the optimal threshold for predicting 3-year mortality, independent of other established variables.

Conclusions: High serum sTfR accurately reflects depleted iron stores in bone marrow in patients with HF, and identifies those with a high 3-year mortality.
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http://dx.doi.org/10.1002/ejhf.2036DOI Listing
October 2020

A current and future outlook on upcoming technologies in remote monitoring of patients with heart failure.

Eur J Heart Fail 2020 Oct 27. Epub 2020 Oct 27.

Division of Cardiology and Metabolism - Heart Failure, Cachexia & Sarcopenia, Department of Cardiology, Campus Virchow-Klinikum, Charité - Medical School, Berlin, Germany.

Heart failure is a major health and economic challenge in both developing and developed countries. Despite advances in pharmacological and device therapies for patients with a reduced left ventricular ejection fraction (LVEF) and heart failure, their quality of life and exercise capacity are often persistently impaired, morbidity and mortality remain high and the health economic and societal costs are considerable. For patients with heart failure and preserved LVEF, diuretic management has an essential role for controlling congestion and symptoms, even if no intervention has convincingly shown to reduce morbidity or mortality. Remote monitoring might improve care delivery and clinical outcomes for patients regardless of LVEF. A great variety of innovative remote monitoring technologies and algorithms are being introduced, including patient self-managed testing, wearable devices, technologies either integrated into established clinically indicated therapeutic devices, such as pacemakers and defibrillators, or as stand-alone are in development providing the promise of further improvements in service delivery and clinical outcomes. In this article, we will discuss unmet needs in the management of patients with heart failure, how remote monitoring might contribute to future solutions, and provide an overview of current and novel remote monitoring technologies.
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http://dx.doi.org/10.1002/ejhf.2033DOI Listing
October 2020

Common mechanistic pathways in cancer and heart failure. A scientific roadmap on behalf of the Translational Research Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC).

Eur J Heart Fail 2020 12 12;22(12):2272-2289. Epub 2020 Nov 12.

Institute of Experimental Cardiology, Heidelberg University Hospital, Heidelberg, Germany.

The co-occurrence of cancer and heart failure (HF) represents a significant clinical drawback as each disease interferes with the treatment of the other. In addition to shared risk factors, a growing body of experimental and clinical evidence reveals numerous commonalities in the biology underlying both pathologies. Inflammation emerges as a common hallmark for both diseases as it contributes to the initiation and progression of both HF and cancer. Under stress, malignant and cardiac cells change their metabolic preferences to survive, which makes these metabolic derangements a great basis to develop intersection strategies and therapies to combat both diseases. Furthermore, genetic predisposition and clonal haematopoiesis are common drivers for both conditions and they hold great clinical relevance in the context of personalized medicine. Additionally, altered angiogenesis is a common hallmark for failing hearts and tumours and represents a promising substrate to target in both diseases. Cardiac cells and malignant cells interact with their surrounding environment called stroma. This interaction mediates the progression of the two pathologies and understanding the structure and function of each stromal component may pave the way for innovative therapeutic strategies and improved outcomes in patients. The interdisciplinary collaboration between cardiologists and oncologists is essential to establish unified guidelines. To this aim, pre-clinical models that mimic the human situation, where both pathologies coexist, are needed to understand all the aspects of the bidirectional relationship between cancer and HF. Finally, adequately powered clinical studies, including patients from all ages, and men and women, with proper adjudication of both cancer and cardiovascular endpoints, are essential to accurately study these two pathologies at the same time.
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http://dx.doi.org/10.1002/ejhf.2029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894564PMC
December 2020

Role of serum biomarkers in cancer patients receiving cardiotoxic cancer therapies: a position statement from the Cardio-Oncology Study Group of the Heart Failure Association and the Cardio-Oncology Council of the European Society of Cardiology.

Eur J Heart Fail 2020 11 20;22(11):1966-1983. Epub 2020 Oct 20.

Cardio-Oncology Service, Royal Brompton Hospital and Imperial College London, London, UK.

Serum biomarkers are an important tool in the baseline risk assessment and diagnosis of cardiovascular disease in cancer patients receiving cardiotoxic cancer treatments. Increases in cardiac biomarkers including cardiac troponin and natriuretic peptides can be used to guide initiation of cardioprotective treatments for cancer patients during treatment and to monitor the response to cardioprotective treatments, and they also offer prognostic value. This position statement examines the role of cardiac biomarkers in the management of cancer patients. The Cardio-Oncology Study Group of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in collaboration with the Cardio-Oncology Council of the ESC have evaluated the current evidence for the role of cardiovascular biomarkers in cancer patients before, during and after cardiotoxic cancer therapies. The characteristics of the main two biomarkers troponin and natriuretic peptides are discussed, the link to the mechanisms of cardiovascular toxicity, and the evidence for their clinical use in surveillance during and after anthracycline chemotherapy, trastuzumab and HER2-targeted therapies, vascular endothelial growth factor inhibitors, proteasome inhibitors, immune checkpoint inhibitors, cyclophosphamide and radiotherapy. Novel surveillance clinical pathways integrating cardiac biomarkers for cancer patients receiving anthracycline chemotherapy or trastuzumab biomarkers are presented and future direction in cardio-oncology biomarker research is discussed.
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http://dx.doi.org/10.1002/ejhf.2017DOI Listing
November 2020

Correction to: Association of statin use and clinical outcomes in heart failure patients: a systematic review and meta-analysis.

Lipids Health Dis 2020 09 20;19(1):208. Epub 2020 Sep 20.

Department of Hypertension, Medical University of Lodz, Rzgowska, 281/289, 93-338, Łódź, Poland.

An amendment to this paper has been published and can be accessed via the original article.
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http://dx.doi.org/10.1186/s12944-020-01380-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504830PMC
September 2020

Cachexia, muscle wasting, and frailty in cardiovascular disease.

Eur J Heart Fail 2020 12 14;22(12):2314-2326. Epub 2020 Oct 14.

Department of Cardiology and Pneumology, University of Göttingen Medical Center, Göttingen, Germany.

The last several years have seen increasing interest in understanding cachexia, muscle wasting, and physical frailty across the broad spectrum of patients with cardiovascular illnesses. This interest originally started in the field of heart failure, but has recently been extended to other areas such as atrial fibrillation, coronary artery disease, peripheral artery disease as well as to patients after cardiac surgery or transcatheter aortic valve implantation. Tissue wasting and frailty are prevalent among many of the affected patients. The ageing process itself and concomitant cardiovascular illness decrease lean mass while fat mass is relatively preserved, making elderly patients particularly prone to develop wasting syndromes and frailty. The aim of this review is to provide an overview of the available knowledge of body wasting and physical frailty in patients with cardiovascular illness, particularly focussing on patients with heart failure in whom most of the available data have been gathered. In addition, mechanisms of wasting and possible therapeutic targets are discussed.
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http://dx.doi.org/10.1002/ejhf.2011DOI Listing
December 2020

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

ESC Heart Fail 2020 10 28;7(5):3086-3094. Epub 2020 Aug 28.

Department of Cardiology and Pneumology, University of Göttingen Medical Center (UMG), Robert-Koch-Strasse 40, Göttingen, D - 37075, Germany.

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 (ALM/height ) 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 ) (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 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 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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http://dx.doi.org/10.1002/ehf2.12936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524247PMC
October 2020

Muscle wasting as an independent predictor of survival in patients with chronic heart failure.

J Cachexia Sarcopenia Muscle 2020 10 6;11(5):1242-1249. Epub 2020 Aug 6.

Division of Cardiology and Metabolism, Department of Cardiology and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Charité-Universitätsmedizin Berlin (CVK), Berlin, Germany.

Background: Skeletal muscle wasting is an extremely common feature in patients with heart failure, affecting approximately 20% of ambulatory patients with even higher values during acute decompensation. Its occurrence is associated with reduced exercise capacity, muscle strength, and quality of life. We sought to investigate if the presence of muscle wasting carries prognostic information.

Methods: Two hundred sixty-eight ambulatory patients with heart failure (age 67.1 ± 10.9 years, New York Heart Association class 2.3 ± 0.6, left ventricular ejection fraction 39 ± 13.3%, and 21% female) were prospectively enrolled as part of the Studies Investigating Co-morbidities Aggravating Heart Failure. Muscle wasting as assessed using dual-energy X-ray absorptiometry was present in 47 patients (17.5%).

Results: During a mean follow-up of 67.2 ± 28.02 months, 95 patients (35.4%) died from any cause. After adjusting for age, New York Heart Association class, left ventricular ejection fraction, creatinine, N-terminal pro-B-type natriuretic peptide, and iron deficiency, muscle wasting remained an independent predictor of death (hazard ratio 1.80, 95% confidence interval 1.01-3.19, P = 0.04). This effect was more pronounced in patients with heart failure with reduced than in heart failure with preserved ejection fraction.

Conclusions: Muscle wasting is an independent predictor of death in ambulatory patients with heart failure. Clinical trials are needed to identify treatment approaches to this co-morbidity.
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http://dx.doi.org/10.1002/jcsm.12603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567155PMC
October 2020

Pathophysiological mechanisms of statin-associated myopathies: possible role of the ubiquitin-proteasome system.

J Cachexia Sarcopenia Muscle 2020 10 2;11(5):1177-1186. Epub 2020 Aug 2.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Statins are the cornerstone of pharmacotherapy for atherosclerotic cardiovascular disease. While these drugs are generally safe, treatment adherence is not optimal in a considerable proportion of patients because of the adverse effects on skeletal muscles in the forms of myopathy, myalgia, muscular pain, nocturnal muscle cramping, weakness, and rare rhabdomyolysis.

Methods: For the purpose of this narrative review, we searched for the literature suggesting the involvement of the ubiquitin-proteasome system in the development of statin-induced myopathy.

Results: Statins have been shown to up-regulate the expression of the muscle-specific ubiquitin-proteasome system as the major non-lysosomal intracellular protein degradation system. It has been postulated that statins may provoke instability in the myocyte cell membrane when subjected to eccentric exercise stress, triggering activation of intracellular proteolytic cascades and changes in protein degradation machinery. This is accompanied by the up-regulation of a series of genes implicated in protein catabolism, in addition to those of the ubiquitin-proteasome system.

Conclusions: Based on the available literature, it seems that the involvement of ubiquitin-proteasome system is potentially implicated in the pathophysiology of statin-induced myopathy.
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http://dx.doi.org/10.1002/jcsm.12579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567138PMC
October 2020

Acute effects of oral triglyceride load on dynamic changes in peripheral endothelial function in heart failure patients with reduced ejection fraction and healthy controls.

Nutr Metab Cardiovasc Dis 2020 10 2;30(11):1961-1966. Epub 2020 Jun 2.

Berlin Institute of Health Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, Germany; Department of Cardiology (Virchow Klinikum), Charité Universitätsmedizin Berlin, German Centre for Cardiovascular Research (DZHK), Partner site Berlin, Germany; Center for Stroke Research Berlin, Charité Universitätsmedizin Berlin (CSB), Germany. Electronic address:

Bachground: Postprandial hyperlipaemia impairs endothelial function, possibly via oxidative-stress-mediated mechanisms. The aim of this study was to evaluate the acute effects of an oral triglyceride load (OTGL) on peripheral endothelial function in heart failure patients with reduced ejection fraction (HFrEF) compared to healthy controls.

Design: Prospective cross-sectional.

Methods: We enrolled 47 patients with HFrEF and 20 healthy controls. Peripheral endothelial function was assessed with EndoPAT2000 technology using a reactive hyperaemia index (RHI) and pulse wave amplitude (PWA) at baseline (after 8-h overnight fasting) as well as 1, 2, 3 and 4-h post-OTGL consumption (250-ml cream drink). Pulse wave amplitude index (PWAI) was calculated as a ratio of PWA at each time point to the baseline PWA.

Results: RHI at baseline was lower in HFrEF patients compared to controls (1.7 ± 0.3 and 2.3 ± 0.6, respectively; P = 0.001). The OTGL accounted for a physiologic increase in PWA in healthy controls (p = 0.01), but this change was not observed in HFrEF patients. After 4 h, vasodilator response was significantly increased in healthy controls but not patients with HFrEF (2.3 ± 1.3 vs. 1.3 ± 0.8 respectively, P < 0.05).

Conclusions: The main finding of this study was the impaired postprandial dynamic changes in peripheral endothelial function in patients with HFrEF compared to healthy controls. A high-fat load that caused acute hypertriglyceridaemia significantly increased resting blood flow and peak flow at reactive hyperaemia in healthy subjects. By contrast, patients with HFrEF exhibited impaired dynamic changes in peripheral endothelial function after oral triglyceride load.
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http://dx.doi.org/10.1016/j.numecd.2020.05.018DOI Listing
October 2020

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).

Eur J Heart Fail 2020 09 21;22(9):1504-1524. Epub 2020 Aug 21.

National Heart and Lung Institute, Imperial College, London, UK.

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.
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http://dx.doi.org/10.1002/ejhf.1957DOI Listing
September 2020

Heart failure and sleep-disordered breathing: susceptibility to reduced muscle strength and preclinical congestion (SICA-HF cohort).

ESC Heart Fail 2020 10 23;7(5):2063-2070. Epub 2020 Jun 23.

Department of Cardiology and Pneumology, Germany and German Centre for Cardiovascular Research (DZHK), partner site Göttingen, University of Göttingen Medical Centre, Göttingen, Germany.

Aims: Increased sympathetic activation in patients with heart failure (HF) and sleep-disordered breathing (SDB) provokes cardiac decompensation and protein degradation and could lead to muscle wasting and muscle weakness. The aim of this study was to investigate the differences in body composition, muscle function, and the susceptibility of preclinical congestion among patients with HF and SDB compared with those without SDB.

Methods And Results: We studied 111 outpatients with stable HF who were enrolled into the Studies Investigating Co-morbidities Aggravating Heart Failure. Echocardiography, short physical performance battery (SPPB), cardiopulmonary exercise testing, dual-energy X-ray absorptiometry, bioelectrical impedance analysis (BIA), tests of muscle strength, and polygraphy were performed. SDB was defined as apnoea/hypopnoea index (AHI) >5 per hour of sleep. Central sleep apnoea (CSA) and obstructive sleep apnoea (OSA) were defined as AHI >50% of central or obstructive origin, respectively. A total of 74 patients (66.7%) had any form of SDB [CSA (24 patients, 32.4%), OSA (47 patients, 63.5%)]. Patients with SDB showed increased muscle weakness (chair stand), reduced muscle strength, and lower values of SPPB score (P < 0.05). Patients with SDB did not show overt clinical signs of cardiac decompensation compared with those without SDB (P > 0.05) but had increased amounts of water (total body water, intracellular, and extracellular) measured using BIA (P < 0.05). Increased amounts of total body water were associated with the severity of SDB and inversely with muscle strength and exercise capacity measured by anaerobic threshold (P < 0.05). Altogether, 17 patients had muscle wasting. Of these, 11 (65%) patients had SDB (statistically not significant).

Conclusions: SDB is highly prevalent in patients with HF. Patients with SDB have lower muscle strength and tend to be more susceptible to preclinical congestion.
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http://dx.doi.org/10.1002/ehf2.12798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524208PMC
October 2020

Selective androgen receptor modulators (SARMs) as pharmacological treatment for muscle wasting in ongoing clinical trials.

Expert Opin Investig Drugs 2020 Aug 18;29(8):881-891. Epub 2020 Jun 18.

Department of Cardiology and Pneumology, University of Göttingen Medical Center , Göttingen, Germany.

Introduction: Skeletal muscle wasting is a frequent clinical problem encountered in patients with chronic diseases. Increased levels of inflammatory markers play a role in the imbalance between muscle protein synthesis and degradation. Although testosterone has long been proposed as a treatment for patients with muscle wasting, undesirable side effects have raised concerns about prostatic hypertrophy in men as well as virilization in women. Selective androgen receptor modulators (SARMs) have demonstrated similar results like testosterone at improving lean body mass (LBM) with less side effects on androgen-dependent tissue.

Areas Covered: This review outlines the ongoing clinical development in the field of SARMs and their effectiveness in improving body composition and physical function. The included articles were collected at pubmed.gov and analyzed integrally.

Expert Opinion: There is an unmet clinical need for safe and effective anabolic compounds such as SARMs. Despite the effect on LBM shown by SARMs in phase II clinical trials, results on improved physical function and muscle strength are still lacking and long-term outcomes have to be assessed in these patients. Moreover, there is a need to determine the effect of resistance exercise training and protein intake associated with SARMs in the treatment of patients with muscle wasting.
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http://dx.doi.org/10.1080/13543784.2020.1777275DOI Listing
August 2020

Baseline cardiovascular risk assessment in cancer patients scheduled to receive cardiotoxic cancer therapies: a position statement and new risk assessment tools from the Cardio-Oncology Study Group of the Heart Failure Association of the European Society of Cardiology in collaboration with the International Cardio-Oncology Society.

Eur J Heart Fail 2020 11 6;22(11):1945-1960. Epub 2020 Aug 6.

Cardio-Oncology Center of Excellence, Washington University in St Louis, St Louis, MO, USA.

This position statement from the Heart Failure Association of the European Society of Cardiology Cardio-Oncology Study Group in collaboration with the International Cardio-Oncology Society presents practical, easy-to-use and evidence-based risk stratification tools for oncologists, haemato-oncologists and cardiologists to use in their clinical practice to risk stratify oncology patients prior to receiving cancer therapies known to cause heart failure or other serious cardiovascular toxicities. Baseline risk stratification proformas are presented for oncology patients prior to receiving the following cancer therapies: anthracycline chemotherapy, HER2-targeted therapies such as trastuzumab, vascular endothelial growth factor inhibitors, second and third generation multi-targeted kinase inhibitors for chronic myeloid leukaemia targeting BCR-ABL, multiple myeloma therapies (proteasome inhibitors and immunomodulatory drugs), RAF and MEK inhibitors or androgen deprivation therapies. Applying these risk stratification proformas will allow clinicians to stratify cancer patients into low, medium, high and very high risk of cardiovascular complications prior to starting treatment, with the aim of improving personalised approaches to minimise the risk of cardiovascular toxicity from cancer therapies.
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http://dx.doi.org/10.1002/ejhf.1920DOI Listing
November 2020