OBJECTIVES:The present sub-analysis from the randomized UDDC-Radial-Trial sought to compare one-catheter concepts (OCC) with two-catheter concepts (TCC) in different patient subgroups, particularly in those depending on gender and age. BACKGROUND:There is an ongoing debate regarding potential performance differences of OCC compared to TCC for transradial coronary angiography in specific patient subgroups. METHODS:The randomized UDDC-Radial-Trial enrolled a total of 300 patients planed for coronary angiography in a 2:1 ratio to either OCC by Tiger II (n = 100) and BLK (n = 100) or TCC by Judkins (n = 100) catheters. Predefined patient subgroups stratified for age, gender and patient constitution were analyzed with regard to the primary outcome measure of time required for a complete coronary angiography. RESULTS:In male patients time for coronary angiography was significantly shorter in the TCC group compared to the OCC group (510 ± 37 s vs. 615 ± 35 s; p = 0.046). No difference between the catheter concepts was observed in the subset of female patients (525 ± 34 s vs. 583 ± 54 s; p = 0.43). TCC was associated with shorter coronary angiography time in patients aged <71 years compared to OCC (462 ± 23 s vs. 570 ± 38 s; p = 0.018). In patients ≥72 years of age no difference was detected (573 ± 41 s vs. 636 ± 45 s; p = 0.31). Other subgroups showed no relevant differences in angiography time among OCC and TCC. CONCLUSIONS:The present subgroup analysis from the UDDC-radial trial demonstrates the use of OCC in transradial diagnostic angiography to be inferior compared to TCC in terms of angiography time in younger and male patients.

HomeCirculation: Cardiovascular InterventionsVol. 14, No. 9Evaluation of Cerebral Thromboembolism After Transcatheter Aortic Valve Replacement (EARTH TAVR): A Serial Magnetic Resonance Imaging Evaluation as Substudy of the GALILEO Trial Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessLetterPDF/EPUBEvaluation of Cerebral Thromboembolism After Transcatheter Aortic Valve Replacement (EARTH TAVR): A Serial Magnetic Resonance Imaging Evaluation as Substudy of the GALILEO Trial Georg Marcus Fröhlich, MD Matthias Endres, MD Volkmar Falk, MD Lisa Steinbeck, MD Aslihan Erbay, MD Verena Stangl, MD Jochen Wöhrle, MD Tanja K. Rudolph, MD Tobias Geisler, MD Henryk Dreger, MD David Manuel Leistner, MD Christian H. Nolte, MD Axel Unbehaun, MD Axel Linke, MD Jochen B. Fiebach, MD Charles Majoie, MD; PhD Guido Knapp, MSc Karl Georg Haeusler, MD Roxana Mehran, MD Stephan Windecker, MD George D. Dangas, MD, PhD Ulf LandmesserMD Georg Marcus FröhlichGeorg Marcus Fröhlich Correspondence to: Georg Marcus Fröhlich, MD, Department of Cardiology, Charité University Hospital Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany. Email E-mail Address: [email protected] https://orcid.org/0000-0001-5059-3770 , Matthias EndresMatthias Endres https://orcid.org/0000-0001-6520-3720 , Volkmar FalkVolkmar Falk https://orcid.org/0000-0002-7911-8620 , Lisa SteinbeckLisa Steinbeck , Aslihan ErbayAslihan Erbay https://orcid.org/0000-0002-9159-4929 , Verena StanglVerena Stangl , Jochen WöhrleJochen Wöhrle https://orcid.org/0000-0002-9915-1815 , Tanja K. RudolphTanja K. Rudolph https://orcid.org/0000-0001-8839-7476 , Tobias GeislerTobias Geisler , Henryk DregerHenryk Dreger , David Manuel LeistnerDavid Manuel Leistner https://orcid.org/0000-0002-4351-420X , Christian H. NolteChristian H. Nolte https://orcid.org/0000-0001-5577-1775 , Axel UnbehaunAxel Unbehaun , Axel LinkeAxel Linke , Jochen B. FiebachJochen B. Fiebach https://orcid.org/0000-0002-7936-6958 , Charles MajoieCharles Majoie https://orcid.org/0000-0002-7600-9568 , Guido KnappGuido Knapp , Karl Georg HaeuslerKarl Georg Haeusler , Roxana MehranRoxana Mehran https://orcid.org/0000-0002-5546-262X , Stephan WindeckerStephan Windecker https://orcid.org/0000-0003-2653-6762 , George D. DangasGeorge D. Dangas and Ulf LandmesserUlf Landmesser Originally published3 Sep 2021https://doi.org/10.1161/CIRCINTERVENTIONS.121.011074Circulation: Cardiovascular Interventions. 2021;14:e011074Ischemic stroke is an important complication in 2% to 6% of patients within 90 days following transcatheter aortic valve replacement (TAVR).1 The mechanism of cerebral embolism may differ according to the early time period (procedure related within 48 hours of TAVR), or later (nondirectly procedure related, eg, atrial fibrillation [AF] or valve leaflet thrombosis).1 In the PARTNER trial (The Placement of Aortic Transcatheter Valves), 62.5% of the major strokes occurred within the first 48 hours post-TAVR, 25% between days 5 and 30, and 1 stroke was noted after the first month.2 Mobilization of debris from the calcified native aortic valve or the aorta during the implant procedure may explain a significant proportion of early strokes.3 It is well known that TAVR, like surgical aortic valve replacement, may trigger new-onset AF, albeit less frequently. In a series of pivotal trials, 9.1% to 11.7% of patients were diagnosed with new-onset AF within 30 days following the implant, which was associated with increased risk of stroke.4The authors declare that all supporting data are available within the article. The aim of the present study was to evaluate the occurrence and extent of cerebral embolization (total new lesion volume on diffusion-weighted imaging [DWI] and fluid-attenuated inversion recovery imaging) in patients early and 90 days post-TAVR as compared with before TAVR in low- to intermediate-risk patients. Cerebral magnetic resonance imaging (MRI) scans were performed before TAVR, within 48 hours post-TAVR, and after 90 days. Two experienced neuroradiologists (J.B.F. and C.M.) assessed cerebral lesion number and volume, as well as intracerebral microbleedings. DWI hyperintense lesions at baseline were diagnosed as acute infarctions. Lacunar and territorial infarct patterns, either necrosis or hyperintense lesions, were diagnosed as chronic strokes. At post-TAVR MRI, new DWI lesions (compared with baseline) were diagnosed as new acute infarction and associated to the TAVR procedure. At 3-month examination, DWI hyperintense lesions and additional fluid-attenuated inversion recovery hyperintense lesions that were not diagnosed at screening (acute or chronic lesions) were diagnosed as new lesions. The difference between lesion post-TAVR MRI and 3-month MRI represents new lesions. The study was approved by the responsible authority (Bundesinstitut für Arzneimittel und Medizinprodukte, Kurt-Georg-Kiesinger-Allee 3, Bonn, Germany) and an institutional review committee (Landesamt f. Gesundheit und Soziales, Berlin, Germany). All subjects gave informed consent.For continuous variables, means and SDs are reported. For binary variables, absolute numbers and percentages are given. For the primary MRI variables, the medians with 95% nonparametric bootstrap CIs are reported.Between November 2016 and May 2018, 33 patients could finally be included. The mean age was 79.4±5.8 years. Thirteen patients (39%) were men. Eight patients (24%) were diabetic, and 13 patients (39%) were known for congestive heart failure. Ten patients (30%) were known for coronary artery disease. Three patients (9%) had a previous stroke. According to EuroScore II, 26 patients (79%) had a low (<5%) and 6 patients (18%) had an intermediate perioperative surgical risk (5%–10%).Only in two of the presented patients, new-onset AF was documented between the time period >48 hours post-TAVR and the 90-day follow-up.The primary end point demonstrated no difference in new DWI lesion volume but an increase of the fluid-attenuated inversion recovery lesions +3.5 (95% nonparametric bootstrap CI, 2–7) and the fluid-attenuated inversion recovery lesion volume of 0.11 cm3 (0.06–0.34) 90 days after TAVR if compared with baseline (Figure). On average, 5.5 (3–9) new lesions per patient were detected post-TAVR on DWI-MRI scans in comparison to the baseline scan pre-TAVR. While periprocedural cerebral embolism was common following TAVR (DWI lesion volume, 0.32 [0.12–0.67]), no additional lesions were documented at 90 days post-TAVR (Figure). Microbleedings are reasonably viewed as potential safety concern during post-TAVR antithrombotic therapy. We found, however, no concerning associations in our present study.Download figureDownload PowerPointFigure. Cerebral magnetic resonance imaging (MRI) at baseline and post-transcatheter aortic valve replacement (TAVR).A, Fluid-attenuated inversion recovery (FLAIR) cerebral MRI at baseline (red), post-TAVR (green), and after 90 d (blue). Diffusion-weighted imaging (DWI) post-TAVR. B, MRI outcomes. Numbers are presented as median and 95% nonparametric bootstrap CI (NBCI). FUP indicates follow-up.In the GALILEO trial (Global Study Comparing a Rivaroxaban-Based Antithrombotic Strategy to an Antiplatelet-Based Strategy After Transcatheter Aortic Valve Replacement to Optimize Clinical Outcomes), >90% of patients had a low-to-intermediate perioperative risk score.5 Previous post-TAVR cerebral MRI studies reported a higher ischemic brain lesion volume of 1.5 to 4.3cm3 in up to 77% of patients, if compared with our results in a low surgical risk population.1Potential limitations of this study may be the small sample size, a change in the medical regimen in patients with new-onset AF, and a heterogeneity of procedures (several valve-in-valve procedures, use of protection devices in some patients).In summary, in low- to intermediate-risk TAVR patients without an established indication for an oral anticoagulation, cerebral thromboembolic events as assessed by MRI occurred primarily during the periprocedural phase and rarely from the post-TAVR period to 90 days.AcknowledgmentsThe Charité University Hospital Berlin was responsible for the study design and conduct of the study. The Clinical Research Organization (CRO) Cardialysis, Rotterdam, the Netherlands, was responsible for data management. The MRI core lab (Nicolab, Amsterdam, the Netherlands) was responsible for collection and blinded analysis of all cerebral MRI scans.Sources of FundingThis work was supported by Bayer Vital GmbH, Leverkusen.Disclosures Dr Fröhlich reports research grants from Bayer (significant) and speaker honoraria from Amgen and Boehringer Ingelheim (modest). Dr Rudolph reports speaker's honoraria from Boston Scientific, Edwards Lifesciences, Medtronic, and Abbot (modest). Dr Unbehaun has served as proctor to Boston Scientific. Dr Landmesser reports grants from Bayer (significant) and personal fees from Bayer, Boehringer, Daiichy Sankyo, and Pfizer, outside the submitted work (modest). Dr Falk reports consulting fees from Philips; speaker fees from Medtronic, Edwards, St. Jude Medical, and Aesculap; and research funding from Philips, Valtech, Medtronic, Biotronik, and Boston Scientific. Dr Windecker reports personal fees from AstraZeneca and grants from Boston Scientific, Terumo, Abbott, St. Jude, Edwards, and Medtronic. Dr Dangas reports research/research grants from Abbott Laboratories (significant); other from Boston Scientific Corporation; and last stock option payment for Claret (all fully divested; significant). Dr Mehran: Boston Scientific (modest); ownership/partnership/principal: Claret, bought by Boston Scientific (significant); research/research grants from Bayer Healthcare Pharmaceuticals (significant), AstraZeneca Pharmaceuticals (significant), CSL Medtronic (significant), Abbott Laboratories (significant), and Bristol Myers Squibb Company (significant). Dr Geisler reports being on scientific advisory board meetings for Bayer Healthcare, Daiichi Sankyo, Bristol Myers Squibb, AstraZeneca, and Boehringer Ingelheim; Speakers Bureau (commercial) for Bristol Myers Squibb, Pfizer, AstraZeneca, Bayer Healthcare, Boehringer Ingelheim, Medtronic, and Daiichy Sankyo; and funding for travel or speaker honoraria from Bristol Myers Squibb, AstraZeneca, Bayer Healthcare, Boehringer Ingelheim, Medtronic, Daiichy Sankyo, and Edwards Lifescience. Dr Leistner reports speaker honoraria and research grants from Bayer (modest). Dr Nolte has received consulting and lecture fess from Boehringer Ingelheim (honoraria for lectures, modest), W. L. Gore and Associates (honoraria for lectures, modest), Bristol Myers Squibb (honoraria for lectures, modest), Pfizer (honoraria for lectures, modest), and Sanofi (honoraria for lectures, modest). Dr Endres reports grants from Bayer and fees paid to Charité from AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, Amgen, Sanofi, Novartis, and Pfizer, all outside the submitted work. Dr Fiebach has received consulting, lecture, and advisory board fees from Boehringer Ingelheim (modest). Dr Georg Haeusler reports study grants by Bayer Healthcare (significant), a study grant by Sanofi-Aventis (significant), lecture fees from Bayer Healthcare (modest), Sanofi-Aventis (modest), Pfizer, and Bristol Myers Squibb, as well as a consultant relationship with Bayer Healthcare (modest), Pfizer, and Edwards Lifesciences (modest). Dr Linke reports research support from Novartis; consulting fees/honoraria from Medtronic, Abbot, Edwards Lifesciences, Boston Scientific, AstraZeneca, Novartis, Pfizer, Abiomed, Bayer, Boehringer, major stock shareholder: Claret Medical, Picardia, and Transverse Medical. The other authors report no conflicts.FootnotesFor Sources of Funding and Disclosures, see page 984.Correspondence to: Georg Marcus Fröhlich, MD, Department of Cardiology, Charité University Hospital Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany. Email georg.[email protected]deReferences1. Mohammed Imran G, Alexandra L. Understanding neurologic complications following TAVR.Interv Cardiol. 2018; 13:27–32. doi: 10.15420/icr.2017:25:1CrossrefMedlineGoogle Scholar2. Miller DC, Blackstone EH, Mack MJ, Svensson LG, Kodali SK, Kapadia S, Rajeswaran J, Anderson WN, Moses JW, Tuzcu EM, et al.; PARTNER Trial Investigators and Patients; PARTNER Stroke Substudy Writing Group and Executive Committee. Transcatheter (TAVR) versus surgical (AVR) aortic valve replacement: occurrence, hazard, risk factors, and consequences of neurologic events in the PARTNER trial.J Thorac Cardiovasc Surg. 2012; 143:832–843.e13. doi: 10.1016/j.jtcvs.2012.01.055CrossrefMedlineGoogle Scholar3. Schmidt T, Akdag O, Wohlmuth P, Thielsen T, Schewel D, Schewel J, Alessandrini H, Kreidel F, Bader R, Romero M, et al.. Histological findings and predictors of cerebral debris from transcatheter aortic valve replacement: the ALSTER experience.J Am Heart Assoc. 2016; 5:e004399. doi: 10.1161/JAHA.116.004399LinkGoogle Scholar4. Leon MB, Smith CR, Mack MJ, Makkar RR, Svensson LG, Kodali SK, Thourani VH, Tuzcu EM, Miller DC, Herrmann HC, et al.; PARTNER 2 Investigators. Transcatheter or surgical aortic-valve replacement in intermediate-risk patients.N Engl J Med. 2016; 374:1609–1620. doi: 10.1056/NEJMoa1514616CrossrefMedlineGoogle Scholar5. Dangas GD, Tijssen JGP, Wöhrle J, Søndergaard L, Gilard M, Möllmann H, Makkar RR, Herrmann HC, Giustino G, Baldus S, et al.; GALILEO Investigators. A controlled trial of rivaroxaban after transcatheter aortic-valve replacement.N Engl J Med. 2020; 382:120–129. doi: 10.1056/NEJMoa1911425CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails September 2021Vol 14, Issue 9Article InformationMetrics Download: 188 © 2021 American Heart Association, Inc.https://doi.org/10.1161/CIRCINTERVENTIONS.121.011074PMID: 34474587 Originally publishedSeptember 3, 2021 Keywordsinfarctionbrain ischemiaaortic valvethrombosisischemic strokePDF download SubjectsCerebrovascular Disease/StrokeAortic Valve Replacement/Transcatheter Aortic Valve ImplantationIschemic StrokeImagingMagnetic Resonance Imaging (MRI)

Abstract Background Cerebral embolization in patients after Transcatheter Aortic Valve Replacement (TAVR) represents a serious complication, that was related to impaired bioprosthetic leaflet motion and new-onset atrial fibrillation (AFib). Purpose Hereafter we present the first randomized study comparing the effect of an anticoagulation plus antiplatelet with a dual antiplatelet antithrombotic treatment in patients after TAVR on cerebral embolizations as assessed by serial cerebral magnetic resonance imaging (MRI). Methods The Evaluation of Cerebral Thrombembolism After TAVR (EARTH - TAVR) study was conducted as an investigator initiated substudy of the multicenter, randomized, GALILEO study. After successful TAVR, patients without indication for chronic anticoagulation were randomly assigned to rivaroxaban 10mg plus acetylsalicylic acid 75–100mg once-daily or clopidogrel 75mg plus acetylsalicylic acid 75–100mg once-daily. Cerebral MRI scans were performed pre-TAVR as a baseline, post-TAVR (within 24–48 hours after TAVR) and 90 days after TAVR. The MRI protocol included diffusion-weighted (DWI) and fluid-attenuated inversion recovery (FLAIR) imaging. Cerebral embolic lesions were evaluated by an independent cerebral MRI core lab. The primary outcome measure of this study was the occurrence and extent of cerebral embolizations as measured by total volume of new ischaemic cerebral lesions. Results 36 patients were enrolled in the EARTH and the GALILEO study. The DWI MRI scans revealed an increase of cerebral lesions and volume post-TAVR by a median of 4.75 (95% NBCI 2.1–8.9) and 0.26cm3 (95% NBCI 0.11–0.59). On FLAIR imaging, lesion number and volume increased by a median of 3 (95% NBCI 1.5–6) and 0.1 cm3 (95% NBCI 0.04–0.31). At the 90 days MRI scan, there was no statistically significant change in cerebral lesions, if compared to the post-TAVR scan, irrespective of the treatment arm. Conclusion Thromboembolic events occur largely in the periinterventional phase post TAVR. Thereafter, the risk for additional cerebral embolization is low. An additional rivaroxaban therapy beyond antiplatelet inhibition did not impact on cerebral thromboembolism. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Bayer Pharmaceuticals

Die optische Kohärenztomographie (OCT) ist eine innovative intrakoronare Bildgebungstechnik, die eine hochauflösende Darstellung der Koronarstruktur und -morphologie ermöglicht. Dadurch werden eine genaue Darstellung der Koronargefäßwand und zur Koronarintervention (perkutane Koronarintervention [PCI]) eine differenzierte Festlegung des interventionellen Behandlungsziels, ein exaktes Stentsizing und eine Beurteilung des PCI-Resultats möglich. Der vorliegende Beitrag fasst technisch-methodische Grundlagen der OCT-Bildgebung, Grundlagen der OCT-Bildinterpretation, den Einsatz der OCT-Technik zur Koronarintervention und die dem Verfahren aktuell zugrunde liegende Studienevidenz zusammen.

The Use of Different Diagnostic Catheters-Radial-Trial sought to compare the safety and efficacy of one-catheter concepts (OCC) using Tiger II or BLK catheters with two-catheter concepts (TCC) using standard Judkins catheters for transradial coronary angiography. A total of 300 patients planed for coronary angiography were enrolled into this single-center, single-blinded trial. Patients were randomized in a 2:1 ratio to either OCC by Tiger II (n = 100) and BLK (n = 100) or TCC by Judkins (n = 100) catheters. Primary end point was time required to perform a complete coronary angiography. Coronary angiography duration was 603 29 seconds and 552 26 sec in the OCC and the TCC groups (p = 0.052). Fluoroscopy time was longer in the OCC (408 28 sec) as compared with the TCC group (258 28 sec, p = 0.009) and the amount of contrast volume used significantly higher (98 +/- 5 ml vs 67 +/- 4 ml, p < 0.001). Crossover rates were increased in the OCC as compared with the TCC group (37% vs 4 %, p < 0.001). These effects were observed irrespective of OCC catheter type. In conclusion, this study demonstrates that OCC do not reduce angiography time, but are associated with an increased amount of contrast volume and longer fluoroscopy time as compared with TCC. (C) 2018 Elsevier Inc. All rights reserved.

Aims: Intracoronary optical coherence tomography (OCT) imaging allows for high-resolution characterization of coronary lesions. Difficulties in matching cross-sectional OCT-images with angiographic lesion localization may limit optimal clinical utilization. We sought to prospectively assess the impact of a novel system of real-time OCT coregistration with angiography (ACR) on physician decision-making during percutaneous coronary interventions (PCI). Methods and Results: Strategy for PCI (stent - length, - diameter, - strategy, landing zone) and PCI-optimization (stent-malappostion, -underexpansion, edge-dissections, geographical mismatch) was prospectively assessed in 50 patients with 58 coronary lesions after (I) angiography, (II) OCT imaging, and (III) ACR. Preprocedural OCT imaging altered stent-length (58.9%), diameter (33.9%), and PCI-strategy (12.5%) in 40 (71.4%) lesions. The use of ACR resulted in additional changes in PCI strategy in 40.7% of mostly complex lesions in comparison to OCT imaging alone and involved mainly device landing zone (24.1%) and stent length (22.2%). Postprocedural OCT imaging revealed the need for PCI optimization in 52.2% of the lesions, whereas post-procedural ACR had no further impact. Conclusions: Real-time OCT ACR had significant impact on PCI strategy, favoring mainly complete lesion coverage especially in complex lesions.

Anaemia and iron deficiency (ID) are important co-morbidities in patients with chronic heart failure (HF) and both may lead to reduced exercise capacity.Methods: We enrolled 331 out-patients with stable chronic HF (mean age: 64 +/- 11 years, 17% female, left ventricular ejection fraction [LVEF] 35 +/- 13%, bodymass index [BMI] 28.5 +/- 5.2 kg/m(2), New York Heart Association [NYHA] class 2.2 +/- 0.7, chronic kidney disease 35%, glomerular filtration rate 61.7 +/- 20.1mL/min). Anaemia was defined according to World Health Organization criteria (haemoglobin [Hb] < 13 g/dL in men, < 12 g/dL in women). ID was defined as serum ferritin <100 mu g/L or ferritin <300 mu g/L with transferrin saturation (TSAT) <20%. Exercise capacity was assessed as peak oxygen consumption (peak VO2) by spiroergometry and 6-minute walk test (6MWT).Results: A total of 91 (27%) patients died from any cause during a mean follow-up of 18 months. At baseline, 98 (30%) patients presented with anaemia and 149 (45%) patients presented with ID. We observed a significant reduction in exercise capacity in parallel to decreasing Hb levels (r = 0.24, p < 0.001). In patients with anaemia and ID (n = 63, 19%), exercise capacity was significantly lower than in patients with ID or anaemia only. Cox regression analysis showed that after adjusting for NYHA, age, hsCRP and creatinine anaemia is an independent predictor of mortality in patients with HF (hazard ratio [HR]: 0.56, 95% confidence interval [CI]: 0.33-0.97, p = 0.04).Conclusion: The impact of anaemia on reduced exercise capacity and on mortality is stronger than that of ID. Anaemia remained an independent predictor of death after adjusting for clinically relevant variables. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

BACKGROUND:To describe the prevalence of sarcopenia in ambulatory patients with heart failure with preserved ejection fraction (HFpEF) and its relation to reduced exercise capacity, muscle strength, and quality of life (QoL). METHODS AND RESULTS:A total of 117 symptomatic outpatients with HFpEF were prospectively enrolled in Germany, England, and Slovenia as part of the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF). Appendicular skeletal muscle (ASM) mass (the sum of muscle mass in both arms and legs) was assessed by DEXA. Echocardiography, 6-minute walk testing (6-MWT), muscle strength assessment, spiroergometry and QoL evaluation using EQ-5D Questionnaire were performed. Sarcopenia was defined as ASM 2 standard deviations below the mean of a healthy reference group aged 18-40years. Patients were divided into 3 groups according to the E/e' value: ≤8, 9-14, and ≥15. Sarcopenia was detected in 19.7% of all patients. These patients performed worse during 6-MWT (404±116 vs. 307±145m, p=0.003) and showed lower absolute peak oxygen consumption (1579±474 vs. 1211±442mL/min, p<0.05). Both ASM and muscle strength were lowest in patients with E/e' >15 (p<0.05). Higher values of muscle strength/ASM were associated with a better QoL (r=0.5, p<0.0005). Logistic regression showed ASM to be independently associated with reduced distance walked during the 6-MWT adjusted for NYHA, height, left atrium diameter, ferritin and forced expiratory volume in 1s (FEV1) (odds ratio 1.2, p=0.02). CONCLUSION:Sarcopenia affects a clinically relevant proportion of patients with HFpEF. Low ASM is strongly linked to reduced muscle strength, exercise capacity and QoL in these patients.

This article highlights preclinical and clinical studies in the field of wasting disorders that were presented at the 7th Cachexia Conference held in Kobe, Japan, in December 2013. This year, the main topics were the development of new methods and new biomarkers in the field of cachexia and wasting disorders with particular focus on inflammatory pathways, growth differentiation factor-15, myostatin, the ubiquitin proteasome-dependent pathway, valosin and the regulation of ubiquitin-specific protease 19 that is involved in the differentiation of myogenin and myosin heavy chain. This article presents highlights from the development of drugs that have shown potential in the treatment of wasting disorders, particularly the ghrelin receptor agonist anamorelin, the myostatin antagonist REGN1033, the selective androgen receptor modulators enobosarm and TEI-E0001, and the anabolic catabolic transforming agent espindolol. In addition, novel data on the prevalence and detection methods of muscle wasting/sarcopenia are presented, including the D3-creatine dilution method and several new biomarkers.

Anaemia and iron deficiency are important co morbidities and both resulting in reduced exercise capacity. The impact of a new onset of anaemia in the progression of heart failure needs to be defined.A total of 280 patients with stable chronic HF were enrolled and were followed up until the end of the study in April 2014 or until death. Stable HF patients were enrolled with mean age of 67±11 years, 21% female, mean left ventricular ejection fraction (LVEF) was 39±13%, Body Mass Index (BMI) 29.3±5.5 kg/m2 and mean New York Heart Association (NYHA) class 2.3±0.6. Anaemia was defined according to World Health Organization criteria [Haemoglobin (Hb) <13 g/dL in men and <12 g/dL in women]. We defined microcytic anaemia as MCV≤80fl, normocytic anaemia as MCV between 80-96fl and macrocytic anaemia as MCV≥96fl. ID was defined as ferritin <100 μg/L or ferritin <100 <300 μg/L than with transferrin saturation (TSAT) <20%. Exercise capacity was assessed by spiroergometry (peakVO2) and 6 minute walk test (6MWT). A total of 37 (13.2%) Patients died from any cause during follow-up. At baseline a total of 88 (31%) patients were found with anaemia, 140 (50%) were found with ID, 180 (64%) showed heart failure with reduced EF (HFrEF), 63 (23%) were found with cachexia, 83 (30%) showed diabetes mellitus, 107 (38%) were found with renal failure. Of the 88 patients with anaemia at baseline a total of 62 were found with normocytic anaemia, 12 with macrocytic anaemia and 14 microcytic anaemia. In patients with both ID and anaemia (n=60, 21%) it was shown that exercise capacity is more decreased than with ID or anaemia alone. We observed a significant reduction in exercise capacity in parallel to decreasing Hb levels (r=0.299, p<0.001). After first follow up of a mean of 8 month 25 Patients showed a new onset of anaemia. We defined a combined endpoint as death or new onset of anaemia or decreased Hb value about 1g/dl. A total of 76 Patients reached this endpoint after a mean of 26 month. In logistic regression analysis it was shown that peak VO2 (Exp:0.92, 95%CI:0.86-0.98, p=0.01), 6MWT (Exp:0.99, 95%CI:0.99-1.00, p=0.02), NYHA (Exp:1.66, 95%CI:1.09-2.54, p=0.01), LVEF (Exp:0.97, 95%CI:0.95-0.99, p=0.002), present pacemaker devices (Exp:2.17, 95%CI:1.26-3.72, p=0.005) taking aldosteron receptor blockers (ARB) (Exp:1.93, 95%CI:1.13-3.29, p=0.01) were predictors for this endpoint. In multivariate model peak VO2 is an independent predictor for reaching this endpoint after adjusting for age, female gender, renal failure and cachexia. The value representing the optimal cut off for prediction mortality and new anaemia was 14.6 ml/kg*min with a specificity of 74.3% (95%CI: 66.4-81.2) and sensitivity of 49.0% (95%CI: 34.8-63.4).Exercise capacity is an independent predictor of developing anaemia or mortality. The impact of anaemia on reduced exercise capacity is stronger than that of ID.

Patients with heart failure are frequently limited in their exercise capacity. Although this clinical phenomenon is mostly attributed to the failing myocardium, the effects of skeletal muscle wasting should not be underestimated. Muscle wasting may present in the form of loss of muscle mass and function, termed sarcopenia in healthy aging, or in the form of cachexia. Only cachexia is associated with loss of body weight. The mechanisms involved embrace an anabolic-/catabolic imbalance with increased degradation of myofibrils and myocyte apoptosis. Clinical effects include reduced muscle mass, strength and consequently reduced exercise capacity. This article describes the terminology, molecular pathways, prevalence, clinical implications and possible treatment approaches to muscle wasting in patients with heart failure. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting.

Introduction: The aim of this study was to assess the prevalence of liver function test (LFT) abnormalities and their impact on hospital admissions among patients with chronic heart failure (HF). Methods: We prospectively investigated 195 ambulatory chronic HF patients (median age 68.8 [IQR 61.7-74.8] years; 21.5% female, New York Heart Association class 2.3±0.6) with left ventricular ejection fraction [LVEF] ≤40% (70.3%) and LVEF >40% (29.7%). All patients were enrolled between February 2010 and December 2012 at the Charité Medical School Berlin as part of the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF). We measured serum LFTs and creatinine at baseline. Patients were followed-up for 180 days and hospital admissions for cardiovascular (CV) reasons were recorded. Associations between LFTs and hospital admissions were determined using Cox proportional hazard analysis. Results: Overall, 39.0% of patients had at least one abnormal LFT. The most frequent LFT abnormalities were low albumin (below lower limit of normal in 24.6%), elevated gamma-glutamyl transferase (GGT, above upper limit of normal in 27.7%) and elevated direct bilirubin (above upper limit of normal in 13.8%). Patients with advanced HF (NYHA III/IV) had significantly higher prevalence of abnormal GGT, alkaline phosphatase (AP), direct and total bilirubin compared to patients in NYHA I/II (all p ≤0.01), suggesting even more pronounced cholestatic liver dysfunction. A total of 53 (27.2%) subjects were hospitalized for CV reasons during follow-up. Single predictor Cox analysis showed that the following LFTs were predictive of CV hospitalizations: direct bilirubin (hazard ratio [HR] 12.0, 95% confidence interval [CI] 3.3–43.6, p<0.001), total bilirubin (HR 2.3, 95% CI 1.3–3.9), AP as well as aspartate aminotransferase (ASAT). In adjusted multivariable Cox analysis, only direct bilirubin (HR 8.6, 95% CI 1.6–45.9) and ASAT (HR 1.02, 95% CI 1.0003–1.04) carried predictive value (both p≤0.01) independently of age, LVEF and creatinine. Conclusion: Liver dysfunction is relatively frequent in patients with HF with predominance of cholestatic LFT abnormalities. Assessment of LFTs, especially direct bilirubin may help to identify patient with high risk of hospitalization for cardiovascular reasons.