Publications by authors named "Axel Linke"

307 Publications

Evaluation of Cerebral Thromboembolism After Transcatheter Aortic Valve Replacement (EARTH TAVR): A Serial Magnetic Resonance Imaging Evaluation as Substudy of the GALILEO Trial.

Circ Cardiovasc Interv 2021 Sep 3;14(9):e011074. Epub 2021 Sep 3.

Department of Cardiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Germany (G.M.F., L.S., A.E., D.L., U.L.). Klinik und Hochschulambulanz für Neurologie, Charité-Universitätsmedizin Berlin, Germany (M.E.). Center for Stroke Research Berlin, Charité University Hospital Berlin, Campus Benjamin Franklin, CSB Neuroradiology, Germany (M.E., J.B.F.). Department of Cardiac Surgery, German Heart Center Berlin, Department of Cardiothoracic Surgery, Germany (V.F., C.H.N., A.U.). Department of Cardiovascular Surgery, Charité University Hospital Berlin, Campus Virchow, Germany (V.F., A.U.). Department of Health Sciences and Technology, ETH Zurich, Switzerland (V.F.). Department of Cardiology and Angiology, Charité University Hospital Berlin, Germany (V.S., H.D.). Deutsches Zentrum für Herz- und Kreislaufforschung, Partner Site Berlin, Germany (M.E., V.S., H.D., U.L.). Department of Internal Medicine II, University Hospital Ulm, Germany (J.W.). Department of Cardiology, University Hospital Cologne, Germany (T.K.R.). Department of Cardiology, Heart and Diabetes Center NRW, Ruhr University Bochum, Bad Oeynhausen, Germany (T.K.R.). Department of Cardiology and Angiology, University Hospital Tübingen, Germany (T.G.). Department of Cardiology, Leipzig Heart Center, Germany (A.L.). Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, the Netherlands (C.M.). Department of Statistics, Technical University Dortmund, Germany (G.K.). Department of Neurology, Universitätsklinkum Würzburg, Germany (K.G.H.). Interventional Cardiovascular Research and Clinical Trials at the Zena and Michael A. Wiener, Cardiovascular Institute at Mount Sinai School of Medicine, New York, NY (R.M.). Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Switzerland (S.W.). Mount Sinai School of Medicine, New York, NY (G.D.D.). Berlin Institute of Health, Germany (U.L.).

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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.121.011074DOI Listing
September 2021

Long-term Follow-up After Transcatheter Aortic Valve Replacement.

CJC Open 2021 Jul 1;3(7):845-853. Epub 2021 Feb 1.

Herzzentrum Dresden, University Clinic, Technische Universität Dresden, Department of Internal Medicine and Cardiology, Dresden, Germany.

Background: Transcatheter aortic valve replacement (TAVR) has become the standard of care in the majority of patients with symptomatic severe aortic stenosis. Data on long-term mortality and durability of transcatheter heart valves (THVs) beyond 5 years are limited. Our study aimed to assess elderly and high-risk patients' long-term outcomes treated with TAVR in a prospective single-centre registry focusing on the durability of THVs.

Methods: We included 795 patients with severe calcific aortic stenosis treated by transfemoral TAVR between 2006 and 2011. Echocardiography was performed at baseline; discharge; 1 year; and afterward, annually, until the longest available follow-up. Mortality rates were estimated for 1, 5, 6, 7, and 8 years. The rates of structural valve deterioration (SVD) and bioprosthetic valve failure (BVF) were assessed in accordance with consensus definitions. Outcome measures were adjudicated according to Valve Academic Research Consortium-2 (VARC-2).

Results: Median (interquartile range) follow-up time was 1345 (316; 2015) days. One-year, 5-year, 6-year, 7-year, and 8-year overall mortality was 25.4%, 59.0%, 64.6%, 67.9%, and 69.2%, respectively. At 8 years, no significant differences in mortality were found comparing self-expanding vs balloon-expandable valves (69.5% vs 68.0%,  = 0.709) and postdilatation (PD) vs no-PD (69.4% vs 69.2%,  = 0.363). SVD was detected in 26 patients (3.3%), and 19 (2.4%) of the 795 patients had evidence of BVF during follow-up.

Conclusions: Our study demonstrates good long-term results for high-risk patients who were alive up to 8 years after TAVR.
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http://dx.doi.org/10.1016/j.cjco.2021.01.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347830PMC
July 2021

Final 3-year clinical outcomes following transcatheter aortic valve implantation with a supra-annular self-expanding repositionable valve in a real-world setting: Results from the multicenter FORWARD study.

Catheter Cardiovasc Interv 2021 Jul 31. Epub 2021 Jul 31.

Department of Medicine, University of Bonn, Bonn, Germany.

Objectives: The Evolut R FORWARD study confirmed safety and effectivenesss of the Evolut R THV in routine clinical practice out to 1 year. Herein, we report the final 3-year clinical follow up of the FORWARD study.

Background: Transcatheter aortic valve replacement (TAVR) is a proven alternative to surgery in elderly patients with symptomatic severe aortic stenosis. Long-term clinical outcome data with the Evolut R platform are scarce.

Methods: FORWARD is a prospective multicenter observational study that evaluated the Evolut R system in routine clinical practice at 53 centres. Eligible patients had symptomatic native aortic valve stenosis or failed surgical aortic bioprosthesis and elevated operative risk per Heart-Team assessment. TAVR was attempted in 1039 patients.

Results: Mean age was 81.8 ± 6.2 years, 64.9% were women, STS score was 5.5 ± 4.5% and 34.2% were frail. Rates of all-cause mortality and disabling stroke were 24.8% and 4.8% at 3 years. Early need for a new pacemaker implantation after TAVR (all-cause mortality: with new PPI; 21.0% vs. without; 22.8%, p = 0.55) and the presence of > trace paravalvular regurgitation (all-cause mortality: no or trace; 22.0% vs. ≥ mild; 25.5%, p = 0.29) did not affect survival. Between 1 and 3 years incidence rates of valve related intervention, endocarditis and clinically relevant valve thrombosis were low.

Conclusions: The Evolut R valve maintained a favorable safety profile through 3 years in routine clinical practice. Rates of transcatheter heart valve-related adverse events were low.
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http://dx.doi.org/10.1002/ccd.29889DOI Listing
July 2021

Complete Embolic Protection of the Cerebral Arteries: TAVI Despite Large Left Ventricular Thrombus.

JACC Case Rep 2020 Jul 15;2(8):1103-1105. Epub 2020 Jul 15.

Technische Universität Dresden, Department of Internal Medicine and Cardiology, Herzzentrum Dresden, University Clinic, Dresden, Germany.

The presence of a left ventricular (LV) thrombus is considered an absolute contraindication to transcatheter aortic valve implantation (TAVI) because of the very high embolic risk. We report a case of TAVI under complete protection of the cerebral arteries in a patient with a large LV thrombus, severely impaired LV function, and no surgical options. ().
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http://dx.doi.org/10.1016/j.jaccas.2020.05.070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311951PMC
July 2020

Remote proctoring for high-risk coronary interventions with mechanical circulatory support during COVID-19 pandemic and beyond.

Clin Res Cardiol 2021 Sep 22;110(9):1525-1530. Epub 2021 Jun 22.

Herzzentrum Dresden, Department of Internal Medicine and Cardiology, Technische Universität Dresden, Fetscherstr. 76, 01307, Dresden, Germany.

Remote proctoring by advanced digital technologies may help to overcome pandemic, geographic, and resource-related constraints for mentoring and educating interventional cardiology skills. We present a case series of patients undergoing high-risk percutaneous coronary intervention (HR-PCI) with mechanical circulatory support (MCS) guided by remote proctoring to gain insights into a streaming technology platform with regard to video/audio quality, visibility of all structural and imaging details, and delay in transmission. According to our experience, remote proctoring appears to be a reliable, quick, and resource-conserving way to disseminate, educate and improve MCS-supported HR-PCI with implications far beyond the COVID-19 pandemic.
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http://dx.doi.org/10.1007/s00392-021-01890-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217783PMC
September 2021

Cardiac manifestation is evident in chorea-acanthocytosis but different from McLeod syndrome.

Parkinsonism Relat Disord 2021 Jul 24;88:90-95. Epub 2021 May 24.

Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Translational Neurodegeneration Section "Albrecht-Kossel", Department of Neurology, University Medical Center, University of Rostock, Rostock, Germany. Electronic address:

Introduction: We aimed to study the various cardiac manifestations of the two core neuroacanthocytosis (NA) syndromes, namely chorea-acanthocytosis (ChAc) and McLeod syndrome (MLS). So far, cardiac involvement has been described as specific feature only for MLS.

Methods: We studied six patients with ChAc (mean age 44.5 years, five men, one woman) and six patients with MLS (mean age 57.1 years, all men). Cardiac evaluation included echocardiography and/or cardiac magnetic resonance imaging (cardiac MRI), 24-h ECG-recording and examination of cardiac biomarkers.

Results: Cardiac involvement of ChAc was found in four of six patients. Two patients showed mildly reduced left ventricular ejection fraction (LVEF), two other patients mild to moderate left ventricular (LV) dilatation. Neither an increase in ventricular ectopic beats nor ventricular tachycardia were evident in ChAc. Four of five MLS patients showed left ventricle dilatation and reduced left ventricular ejection fraction (LVEF). Two of these, in addition, had critical ventricular tachycardia. High sensitive troponin T was elevated in all patients, for whom data were available (n = 10). In contrast, elevation of high sensitive troponin I was found in one of six ChAc and one of two MLS patients.

Conclusion: For the first time, we reveal cardiac involvement in a cohort of six ChAc patients, while the risk to develop heart failure seems lower than in MLS. Our study confirms the malignant nature of MLS in terms of ventricular arrhythmias and progression to advanced heart failure. Herein, we define disease-specific recommendations for cardiac assessment in both conditions.
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http://dx.doi.org/10.1016/j.parkreldis.2021.05.015DOI Listing
July 2021

Thirty-day outcomes of the Cardioband tricuspid system for patients with symptomatic functional tricuspid regurgitation: The TriBAND study.

EuroIntervention 2021 05 18. Epub 2021 May 18.

University Hospital Bonn, Bonn, Germany.

Background: Severe tricuspid regurgitation (TR) has limited treatment options and is associated with high morbidity and mortality.

Aims: We evaluated the safety and effectiveness of the Cardioband tricuspid valve reconstruction system (Edwards Lifesciences, Irvine, CA, USA) from the ongoing European single-arm, multicentre, prospective TriBAND post-market clinical follow-up study.

Methods: Eligible patients had chronic symptomatic functional TR despite diuretic therapy and were deemed candidates for transcatheter tricuspid repair by the local Heart Team.

Results: Sixty-one patients had ≥severe functional TR. At baseline, 85% of patients were in NYHA Class III-IV, 94% had ≥severe TR (core laboratory-assessed) with 6.8% EuroSCORE II and 53% LVEF. Device success was 96.7%. At discharge, 59% (p<0.001) of patients achieved ≤moderate TR and 78% had at least one grade TR reduction. At 30 days, all-cause mortality and composite MAE rates were 1.6% and 19.7%, respectively; septolateral annular diameter was reduced by 20%, where 69% of patients achieved ≤moderate TR and 85% of patients had at least one grade TR reduction (all p<0.001). Mid-RVEDD, RA volume, and IVC diameter decreased by 10% (p=0.005), 21% (p<0.001), and 11% (p=0.022), respectively; 74% were in NYHA Class I-II (p<0.001) with improvements in overall KCCQ score by 17 points (p<0.001).

Conclusions: In the TriBAND study, the Cardioband tricuspid system demonstrated favourable outcomes at discharge and 30 days in a challenging patient population with symptomatic ≥severe functional TR. Results showed significant reductions in annular diameter and TR severity, accompanied by early evidence of right heart remodelling and improvements in functional status and quality of life.
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http://dx.doi.org/10.4244/EIJ-D-21-00300DOI Listing
May 2021

A randomized evaluation of the TriGuard™ HDH cerebral embolic protection device to Reduce the Impact of Cerebral Embolic LEsions after TransCatheter Aortic Valve ImplanTation: the REFLECT I trial.

Eur Heart J 2021 07;42(27):2670-2679

College of Physicians and Surgeons, Columbia University, New York, NY, USA.

Aims: The REFLECT I trial investigated the safety and effectiveness of the TriGuard™ HDH (TG) cerebral embolic deflection device in patients undergoing transcatheter aortic valve replacement (TAVR).

Methods And Results: This prospective, multicentre, single-blind, 2:1 randomized (TG vs. no TG) study aimed to enrol up to 375 patients, including up to 90 roll-in patients. The primary combined safety endpoint (VARC-2 defined early safety) at 30 days was compared with a performance goal. The primary efficacy endpoint was a hierarchical composite of (i) all-cause mortality or any stroke at 30 days, (ii) National Institutes of Health Stroke Scale (NIHSS) worsening at 2-5 days or Montreal Cognitive Assessment worsening at 30 days, and (iii) total volume of cerebral ischaemic lesions detected by diffusion-weighted magnetic resonance imaging at 2-5 days. Cumulative scores were compared between treatment groups using the Finkelstein-Schoenfeld method. A total of 258 of the planned, 375 patients (68.8%) were enrolled (54 roll-in and 204 randomized). The primary safety outcome was met compared with the performance goal (21.8% vs. 35%, P < 0.0001). The primary hierarchical efficacy endpoint was not met (mean efficacy score, higher is better: -5.3 ± 99.8 TG vs. 11.8 ± 96.4 control, P = 0.31). Covert central nervous system injury was numerically lower with TG both in-hospital (46.1% vs. 60.3%, P = 0.0698) and at 5 days (61.7 vs. 76.2%, P = 0.054) compared with controls.

Conclusion: REFLECT I demonstrated that TG cerebral protection during TAVR was safe in comparison with historical TAVR data but did not meet the predefined effectiveness endpoint compared with unprotected TAVR controls.
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http://dx.doi.org/10.1093/eurheartj/ehab213DOI Listing
July 2021

Stroke Complicating Infective Endocarditis After Transcatheter Aortic Valve Replacement.

J Am Coll Cardiol 2021 May;77(18):2276-2287

Emory University School of Medicine, Atlanta, Georgia, USA.

Background: Stroke is one of the most common and potentially disabling complications of infective endocarditis (IE). However, scarce data exist about stroke complicating IE after transcatheter aortic valve replacement (TAVR).

Objectives: The purpose of this study was to determine the incidence, risk factors, clinical characteristics, management, and outcomes of patients with definite IE after TAVR complicated by stroke during index IE hospitalization.

Methods: Data from the Infectious Endocarditis after TAVR International Registry (including 569 patients who developed definite IE following TAVR from 59 centers in 11 countries) was analyzed. Patients were divided into two groups according to stroke occurrence during IE admission (stroke [S-IE] vs. no stroke [NS-IE]).

Results: A total of 57 (10%) patients had a stroke during IE hospitalization, with no differences in causative microorganism between groups. S-IE patients exhibited higher rates of acute renal failure, systemic embolization, and persistent bacteremia (p < 0.05 for all). Previous stroke before IE, residual aortic regurgitation ≥moderate after TAVR, balloon-expandable valves, IE within 30 days after TAVR, and vegetation size >8 mm were associated with a higher risk of stroke during the index IE hospitalization (p < 0.05 for all). Stroke rate in patients with no risk factors was 3.1% and increased up to 60% in the presence of >3 risk factors. S-IE patients had higher rates of in-hospital mortality (54.4% vs. 28.7%; p < 0.001) and overall mortality at 1 year (66.3% vs. 45.6%; p < 0.001). Surgical treatment was not associated with improved outcomes in S-IE patients (in-hospital mortality: 46.2% in surgical vs. 58.1% in no surgical treatment; p = 0.47).

Conclusions: Stroke occurred in 1 of 10 patients with IE post-TAVR. A history of stroke, short time between TAVR and IE, vegetation size, valve prosthesis type, and residual aortic regurgitation determined an increased risk. The occurrence of stroke was associated with increased in-hospital and 1-year mortality rates, and surgical treatment failed to improve clinical outcomes.
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http://dx.doi.org/10.1016/j.jacc.2021.03.233DOI Listing
May 2021

Ubiquitin-proteasome-system and enzymes of energy metabolism in skeletal muscle of patients with HFpEF and HFrEF.

ESC Heart Fail 2021 Aug 5;8(4):2556-2568. Epub 2021 May 5.

Department of Internal Medicine and Cardiology, Technische Universität Dresden, Heart Center Dresden - University Hospital, Herzzentrum Dresden, Universitätsklinik, Fetscherstraße 76, Dresden, 01307, Germany.

Background: Skeletal muscle (SM) alterations contribute to exercise intolerance in heart failure patients with preserved (HFpEF) or reduced (HFrEF) left ventricular ejection fraction (LVEF). Protein degradation via the ubiquitin-proteasome-system (UPS), nuclear apoptosis, and reduced mitochondrial energy supply is associated with SM weakness in HFrEF. These mechanisms are incompletely studied in HFpEF, and a direct comparison between these groups is missing.

Methods And Results: Patients with HFpEF (LVEF ≥ 50%, septal E/e' > 15 or >8 and NT-proBNP > 220 pg/mL, n = 20), HFrEF (LVEF ≤ 35%, n = 20) and sedentary control subjects (Con, n = 12) were studied. Inflammatory markers were measured in serum, and markers of the UPS, nuclear apoptosis, and energy metabolism were determined in percutaneous SM biopsies. Both HFpEF and HFrEF showed increased proteolysis (MuRF-1 protein expression, ubiquitination, and proteasome activity) with proteasome activity significantly related to interleukin-6. Proteolysis was more pronounced in patients with lower exercise capacity as indicated by peak oxygen uptake in per cent predicted below the median. Markers of apoptosis did not differ between groups. Mitochondrial energy supply was reduced in HFpEF and HFrEF (complex-I activity: -31% and -53%; malate dehydrogenase activity: -20% and -29%; both P < 0.05 vs. Con). In contrast, short-term energy supply via creatine kinase was increased in HFpEF but decreased in HFrEF (47% and -45%; P < 0.05 vs. Con).

Conclusions: Similarly to HFrEF, skeletal muscle in HFpEF is characterized by increased proteolysis linked to systemic inflammation and reduced exercise capacity. Energy metabolism is disturbed in both groups; however, its regulation seems to be severity-dependent.
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http://dx.doi.org/10.1002/ehf2.13405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318515PMC
August 2021

Myocardial strain analysis using cardiac magnetic resonance in patients with calpainopathy.

Orphanet J Rare Dis 2021 04 30;16(1):194. Epub 2021 Apr 30.

Department of Internal Medicine and Cardiology, Herzzentrum Dresden Universitätsklinik, Technische Universität Dresden, Dresden, Germany.

Background: Limb-girdle muscular dystrophy (LGMD) is a genetically and clinically heterogeneous group of rare muscular dystrophies. Subtype 2A (LGMD2A) also known as "calpainopathy" is an inherited autosomal recessive gene defect. Cardiac dysfunction is common in several forms of LGMD. Cardiac involvement in LGMD2A, however, is not clear. The aim of this study was to perform cardiac magnetic resonance (CMR)-based strain analysis in LGMD2A patients, as this is a diagnostic parameter of subclinical cardiac involvement and a powerful independent predictor of mortality. We conducted the largest prospective cardiac magnetic resonance study to date, including 11 genetically verified LGMD2A patients and 11 age- and sex-matched control subjects and performed CMR-based strain analysis of the left and right ventricles.

Results: Left and right global longitudinal strain (GLS) were not significantly different between the two groups and within normal reference ranges (left ventricle: control - 21.8 (5.1) % vs. patients - 22.3 (3.2) %, p = 0.38; right ventricle: control - 26.3 (7.2) % vs. patients - 26.8 (5.8) %, p = 0.85). Also, global circumferential and radial strains did not significantly differ between the two groups (p = 0.95 and p = 0.86, respectively). LGMD2A patients did not show relevant amounts of late gadolinium enhancement (LGE) or malignant ventricular arrhythmias.

Conclusions: No evidence of even subtle cardiac dysfunction is evident form CMR-based strain analysis in LGMD2A patients. Malignant ventricular arrhythmias were not detected. Thus, in case of non-pathological initial echocardiographic and electrocardiographic examination, a less frequent or even no cardiac follow-up may be acceptable in these patients. However, if there are signs and symptoms that suggest an underlying cardiac condition (e.g. palpitations, angina, shortness of breath), this approach needs to be individualized to account for the unknown.
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http://dx.doi.org/10.1186/s13023-021-01826-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086059PMC
April 2021

Valve Academic Research Consortium 3: Updated Endpoint Definitions for Aortic Valve Clinical Research.

J Am Coll Cardiol 2021 Jun 19;77(21):2717-2746. Epub 2021 Apr 19.

Columbia University Irving Medical Center/NewYork-Presbyterian Hospital and Cardiovascular Research Foundation, New York, New York, USA. Electronic address:

Aims: The Valve Academic Research Consortium (VARC), founded in 2010, was intended to (i) identify appropriate clinical endpoints and (ii) standardize definitions of these endpoints for transcatheter and surgical aortic valve clinical trials. Rapid evolution of the field, including the emergence of new complications, expanding clinical indications, and novel therapy strategies have mandated further refinement and expansion of these definitions to ensure clinical relevance. This document provides an update of the most appropriate clinical endpoint definitions to be used in the conduct of transcatheter and surgical aortic valve clinical research.

Methods And Results: Several years after the publication of the VARC-2 manuscript, an in-person meeting was held involving over 50 independent clinical experts representing several professional societies, academic research organizations, the US Food and Drug Administration (FDA), and industry representatives to (i) evaluate utilization of VARC endpoint definitions in clinical research, (ii) discuss the scope of this focused update, and (iii) review and revise specific clinical endpoint definitions. A writing committee of independent experts was convened and subsequently met to further address outstanding issues. There were ongoing discussions with FDA and many experts to develop a new classification schema for bioprosthetic valve dysfunction and failure. Overall, this multi-disciplinary process has resulted in important recommendations for data reporting, clinical research methods, and updated endpoint definitions. New definitions or modifications of existing definitions are being proposed for repeat hospitalizations, access site-related complications, bleeding events, conduction disturbances, cardiac structural complications, and bioprosthetic valve dysfunction and failure (including valve leaflet thickening and thrombosis). A more granular 5-class grading scheme for paravalvular regurgitation (PVR) is being proposed to help refine the assessment of PVR. Finally, more specific recommendations on quality-of-life assessments have been included, which have been targeted to specific clinical study designs.

Conclusions: Acknowledging the dynamic and evolving nature of less-invasive aortic valve therapies, further refinements of clinical research processes are required. The adoption of these updated and newly proposed VARC-3 endpoints and definitions will ensure homogenous event reporting, accurate adjudication, and appropriate comparisons of clinical research studies involving devices and new therapeutic strategies.
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http://dx.doi.org/10.1016/j.jacc.2021.02.038DOI Listing
June 2021

Valve Academic Research Consortium 3: updated endpoint definitions for aortic valve clinical research.

Eur Heart J 2021 05;42(19):1825-1857

Columbia University Irving Medical Center/NewYork-Presbyterian Hospital and Cardiovascular Research Foundation, New York, NY, USA.

Aims: The Valve Academic Research Consortium (VARC), founded in 2010, was intended to (i) identify appropriate clinical endpoints and (ii) standardize definitions of these endpoints for transcatheter and surgical aortic valve clinical trials. Rapid evolution of the field, including the emergence of new complications, expanding clinical indications, and novel therapy strategies have mandated further refinement and expansion of these definitions to ensure clinical relevance. This document provides an update of the most appropriate clinical endpoint definitions to be used in the conduct of transcatheter and surgical aortic valve clinical research.

Methods And Results: Several years after the publication of the VARC-2 manuscript, an in-person meeting was held involving over 50 independent clinical experts representing several professional societies, academic research organizations, the US Food and Drug Administration (FDA), and industry representatives to (i) evaluate utilization of VARC endpoint definitions in clinical research, (ii) discuss the scope of this focused update, and (iii) review and revise specific clinical endpoint definitions. A writing committee of independent experts was convened and subsequently met to further address outstanding issues. There were ongoing discussions with FDA and many experts to develop a new classification schema for bioprosthetic valve dysfunction and failure. Overall, this multi-disciplinary process has resulted in important recommendations for data reporting, clinical research methods, and updated endpoint definitions. New definitions or modifications of existing definitions are being proposed for repeat hospitalizations, access site-related complications, bleeding events, conduction disturbances, cardiac structural complications, and bioprosthetic valve dysfunction and failure (including valve leaflet thickening and thrombosis). A more granular 5-class grading scheme for paravalvular regurgitation (PVR) is being proposed to help refine the assessment of PVR. Finally, more specific recommendations on quality-of-life assessments have been included, which have been targeted to specific clinical study designs.

Conclusions: Acknowledging the dynamic and evolving nature of less-invasive aortic valve therapies, further refinements of clinical research processes are required. The adoption of these updated and newly proposed VARC-3 endpoints and definitions will ensure homogenous event reporting, accurate adjudication, and appropriate comparisons of clinical research studies involving devices and new therapeutic strategies.
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http://dx.doi.org/10.1093/eurheartj/ehaa799DOI Listing
May 2021

Sacubitril/Valsartan Improves Diastolic Function But Not Skeletal Muscle Function in a Rat Model of HFpEF.

Int J Mol Sci 2021 Mar 30;22(7). Epub 2021 Mar 30.

Laboratory of Molecular and Experimental Cardiology, TU Dresden, Heart Center Dresden, 01307 Dresden, Germany.

The angiotensin receptor/neprilysin inhibitor Sacubitril/Valsartan (Sac/Val) has been shown to be beneficial in patients suffering from heart failure with reduced ejection fraction (HFrEF). However, the impact of Sac/Val in patients presenting with heart failure with preserved ejection fraction (HFpEF) is not yet clearly resolved. The present study aimed to reveal the influence of the drug on the functionality of the myocardium, the skeletal muscle, and the vasculature in a rat model of HFpEF. Female obese ZSF-1 rats received Sac/Val as a daily oral gavage for 12 weeks. Left ventricle (LV) function was assessed every four weeks using echocardiography. Prior to organ removal, invasive hemodynamic measurements were performed in both ventricles. Vascular function of the carotid artery and skeletal muscle function were monitored. Sac/Val treatment reduced E/é ratios, left ventricular end diastolic pressure (LVEDP) and myocardial stiffness as well as myocardial fibrosis and heart weight compared to the obese control group. Sac/Val slightly improved endothelial function in the carotid artery but had no impact on skeletal muscle function. Our results demonstrate striking effects of Sac/Val on the myocardial structure and function in a rat model of HFpEF. While vasodilation was slightly improved, functionality of the skeletal muscle remained unaffected.
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http://dx.doi.org/10.3390/ijms22073570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036273PMC
March 2021

Exercise training and high-sensitivity cardiac troponin T in patients with heart failure with reduced ejection fraction.

ESC Heart Fail 2021 06 23;8(3):2183-2192. Epub 2021 Mar 23.

Department of Clinical and Molecular Medicine, NTNU - Norwegian University of Science and Technology, Trondheim, Norway.

Aims: Whether an exercise training intervention is associated with reduction in long-term high-sensitivity cardiac troponin T (hs-cTnT) concentration (a biomarker of subclinical myocardial injury) in patients with heart failure with reduced ejection fraction (HFrEF) is unknown. The aims were to determine (i) the effect of a 12 week endurance exercise training intervention with different training intensities on hs-cTnT in stable patients with HFrEF (left ventricular ejection fraction ≤ 35%) and (ii) associations between hs-cTnT and peak oxygen uptake (VO ).

Methods And Results: In this sub-study of the SMARTEX-HF trial originally including 261 patients from nine European centres, 213 eligible patients were included after withdrawals and appropriate exclusions [19% women, mean age 61.2 years (standard deviation: 11.9)], randomized to high-intensity interval training (HIIT; n = 77), moderate continuous training (MCT; n = 63), or a recommendation of regular exercise (RRE; n = 73). Hs-cTnT measurements and clinical data acquired before (BL) and after a 12 week exercise training intervention (12 weeks) and at 1 year follow-up (1 year) were analysed using multivariable mixed models. Baseline hs-cTnT was above the 99th percentile upper reference limit of 14 ng/L in 35 (48%), 35 (56%), and 49 (64%) patients in the RRE, MCT, and HIIT groups, respectively. Median hs-cTnT was 16 ng/L at BL, 14 ng/L at 12 weeks, and 14 ng/L at 1 year. Hs-cTnT was statistically significantly reduced at 12 weeks in a model adjusted for randomization group, centre and VO , and after further adjustment in the final model that also included age, sex, creatinine concentrations, N-terminal pro-brain natriuretic peptide, smoking, and heart failure treatment. The mean reduction from BL to 12 weeks in the final model was 1.1 ng/L (95% confidence interval: 1.0-1.2 ng/L, P < 0.001), and the reduction was maintained at 1 year with a mean reduction from BL to 1 year of 1.1 ng/L (95% confidence interval: 1.0-1.1 ng/L, P = 0.025). Randomization group was not associated with hs-cTnT at any time point (overall test: P = 0.20, MCT vs. RRE: P = 0.81, HIIT vs. RRE: P = 0.095, interaction time × randomization group: P = 0.88). Independent of time point, higher VO correlated with lower hs-cTnT (mean reduction over all time points: 0.2 ng/L per increasing mL·kg ·min , P = 0.002), without between-group differences (P = 0.19).

Conclusions: In patients with stable HFrEF, a 12 week exercise intervention was associated with reduced hs-cTnT in all groups when adjusted for clinical variables. Higher VO correlated with lower hs-cTnT, suggesting a positive long-term effect of increasing VO on subclinical myocardial injury in HFrEF, independent of training programme.
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http://dx.doi.org/10.1002/ehf2.13310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120390PMC
June 2021

Frailty is associated with chronic inflammation and pro-inflammatory monocyte subpopulations.

Exp Gerontol 2021 07 17;149:111317. Epub 2021 Mar 17.

Internal medicine, cardiology and intensive care medicine, Heart Center Dresden, Technical University Dresden, Dresden, Germany. Electronic address:

Aim Of The Study: Frail patients with high grade aortic valve stenosis (AS) undergoing Transcatheter Aortic Valve Implantation (TAVI) have an increased mortality. A connection between frailty and inflammation has been suggested. Monocyte subpopulations are associated with both cardiovascular diseases and chronic inflammatory diseases. This study investigates the association of frailty with monocyte subpopulations and systemic inflammatory parameters in elderly patients undergoing TAVI.

Methods: A total of 120 patients with symptomatic AS was examined. Before TAVI implantation, frailty was assessed by a bedside evaluation (eyeball test). In all patients a flow cytometry analysis has been performed. Monocyte subpopulations were defined as follows: classical (CD14CD16), intermediate (CD14CD16) and non-classical (CD14CD16). Expression of CD11b was measured as a marker for monocyte activation. Pro-inflammatory cytokines such as interleukin IL-8, as well as CRP were measured with Cytometric Bead Array or standard laboratory methods.

Results: 28 out of 120 patients were frail. These patients showed both, signs of elevated chronic systemic inflammation reflected by elevated CRP (3.7 (1.4-5.4) vs. 5.9 (3.7-29.1), p = 0.001) and an elevated level of intermediate monocytes (37 (24-54) vs. 53 (47-63), p = 0.001). At 6 months after TAVI, 19 of 120 patients died, primarily without relevant dysfunction of the implanted aortic valve. Mortality was significantly higher in the frail as compared with non-frail patients (9 of 28 frail patients vs. 10 of 92 non frail patients, p < 0.001). A binary logistic regression analysis validated frailty and intermediate monocytes as independent predictors for early mortality after TAVI.

Conclusion: Chronic systemic inflammation and increased levels of intermediate monocytes are associated with frailty in old patients with severe aortic valve stenosis. Both the syndrome of frailty and elevated intermediate monocytes showed an association with early mortality after TAVI.
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http://dx.doi.org/10.1016/j.exger.2021.111317DOI Listing
July 2021

Temporal Trends, Characteristics, and Outcomes of Infective Endocarditis After Transcatheter Aortic Valve Replacement.

Clin Infect Dis 2021 Mar 18. Epub 2021 Mar 18.

Hospital Vall d'Hebron, Barcelona, Spain.

Background: Procedural improvements combined with the contemporary clinical profile of patients undergoing transcatheter aortic valve replacement (TAVR) may have influenced the incidence and outcomes of infective endocarditis (IE) following TAVR. We aimed to determine the temporal trends, characteristics, and outcomes of IE post-TAVR.

Methods: Observational study including 552 patients presenting definite IE post-TAVR. Patients were divided in 2 groups according to the timing of TAVR (historical cohort [HC]: before 2014; contemporary cohort [CC]: after 2014).

Results: Overall incidence rates of IE were similar in both cohorts (CC vs HC: 5.45 vs 6.52 per 1000 person-years; P = .12), but the rate of early IE was lower in the CC (2.29‰ vs 4.89‰, P < .001). Enterococci were the most frequent microorganism. Most patients presented complicated IE ( CC: 67.7%; HC: 69.6%; P = .66), but the rate of surgical treatment remained low (CC: 20.7%; HC: 17.3%; P = .32). The CC exhibited lower rates of in-hospital acute kidney injury (35.1% vs 44.6%; P = .036) and in-hospital (26.6% vs 36.4%; P = .016) and 1-year (37.8% vs 53.5%; P < .001) mortality. Higher logistic EuroScore, Staphylococcus aureus etiology, and complications (stroke, heart failure, and acute renal failure) were associated with in-hospital mortality in multivariable analyses (P < .05 for all).

Conclusions: Although overall IE incidence has remained stable, the incidence of early IE has declined in recent years. The microorganism, high rate of complications, and very low rate of surgical treatment remained similar. In-hospital and 1-year mortality rates were high but progressively decreased over time.
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http://dx.doi.org/10.1093/cid/ciaa1941DOI Listing
March 2021

Pharmacological Pre- and Postconditioning With Levosimendan Protect H9c2 Cardiomyoblasts From Anoxia/Reoxygenation-induced Cell Death via PI3K/Akt Signaling.

J Cardiovasc Pharmacol 2021 03;77(3):378-385

Clinic for Cardiology, Angiology, Pneumology, Nephrology and Internal Intensive Care, Hanau, Germany.

Abstract: The calcium sensitizer levosimendan is indicated for the hemodynamic stabilization of patients with acutely decompensated heart failure and has been shown to be protective against reperfusion injury after myocardial infarction. However, affected forms of cell death and underlying signaling pathways remain controversial. Therefore, the aim of this study was to examine the influence of levosimendan preconditioning and postconditioning on anoxia/reoxygenation-induced apoptosis, necrosis, and autophagy in H9c2 myoblasts. To mimic conditions of myocardial ischemia/reperfusion, rat cardiac H9c2 myoblasts were exposed to anoxia/starvation, followed by reoxygenation/refeeding. Apoptosis, necrosis, autophagy, cell viability, survival signaling, and mitochondrial permeability transition pore (mPTP) opening were measured. Both, pharmacological preconditioning and postconditioning with levosimendan were capable to reduce apoptosis as well as necrosis in stressed H9c2 cells. However, preconditioning showed to have the stronger impact compared with postconditioning. Moreover, levosimendan preconditioning increased autophagy, suggesting enhanced repair processes initiated by the early presence of the drug. Underlying mechanisms differ between both interventions: Although both are associated with PI3/Akt activation and reduced mPTP opening, only postconditioning but not preconditioning depended on mKATP activation. This variation might indicate that a pharmacological treatment after the onset of reoxygenation at least in part directly addresses mitochondrial structures for protection. In conclusion, we demonstrate that both pharmacological preconditioning and postconditioning with levosimendan protect anoxia/reoxygenation-stressed cells but differ in the underlying mechanisms. These results are decisive to obtain more insights into the beneficial effects of levosimendan in the treatment of reperfusion-mediated damage.
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http://dx.doi.org/10.1097/FJC.0000000000000969DOI Listing
March 2021

Cardiac conduction abnormalities in patients with degenerated bioprostheses undergoing transcatheter aortic valve-in-valve implantations and their impact on long-term outcomes.

Int J Cardiol 2021 05 14;330:16-22. Epub 2021 Feb 14.

Department of Cardiac Surgery and Transplantology, Poznan University of Medical Sciences, Poznan, Poland.

Background: The relationship between preoperative cardiac conduction abnormalities (CCA) and long-term outcomes after transcatheter aortic valve-in-valve implantation (TAVI-VIV) remains unclear. The aim of the study was to evaluate the effects of preoperative CCA on mortality and morbidity after TAVI-VIV and to estimate the impact of new-onset CCA on postoperative outcomes.

Methods: Between 2011 and 2020, 201 patients with degenerated aortic bioprostheses were qualified for TAVI-VIV procedures in two German heart centers. Cases with previously implanted permanent rhythm-controlling devices were excluded (n = 53). A total of 148 subjects met the eligibility criteria and were divided into 2 study groups according to the presence of preexisting CCA (CCA (n = 84) and non-CCA (n = 64), respectively). Early and late mortality and morbidity were evaluated. Follow-up functional status was assessed according to New York Heart Association (NYHA) classification.

Results: There were no procedural deaths. TAVI-VIV related new-onset CCAs were observed in 35.8% patients. The 30-day permanent pacemaker implantation rate was 1.6% in non-CCA vs 9.5% in CCA group (p = 0.045). Preexisting right bundle-branch block (OR:5.01; 95%CI, 1.05-23.84) and first-degree atrioventricular block (OR:4.55; 95%CI, 1.10-18.73) were independent predictors of new pacemaker implantation. One-year and five-year probability of survival were comparable in CCA and non-CCA groups: 90.3% vs 91.8% and 68.2% vs 74.3%, respectively. Surviving patients with preexisting and new-onset CCA had a worse functional status according to NYHA classification at follow-up.

Conclusion: Preexisting and new-onset postoperative CCAs did not affect early and late mortality after TAVI-VIV procedures, however, they may have a negative impact on late functional status.
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http://dx.doi.org/10.1016/j.ijcard.2021.02.029DOI Listing
May 2021

Effect of High-Intensity Interval Training, Moderate Continuous Training, or Guideline-Based Physical Activity Advice on Peak Oxygen Consumption in Patients With Heart Failure With Preserved Ejection Fraction: A Randomized Clinical Trial.

JAMA 2021 02;325(6):542-551

Department of Prevention and Sports Medicine, University Hospital Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.

Importance: Endurance exercise is effective in improving peak oxygen consumption (peak V̇o2) in patients with heart failure with preserved ejection fraction (HFpEF). However, it remains unknown whether differing modes of exercise have different effects.

Objective: To determine whether high-intensity interval training, moderate continuous training, and guideline-based advice on physical activity have different effects on change in peak V̇o2 in patients with HFpEF.

Design, Setting, And Participants: Randomized clinical trial at 5 sites (Berlin, Leipzig, and Munich, Germany; Antwerp, Belgium; and Trondheim, Norway) from July 2014 to September 2018. From 532 screened patients, 180 sedentary patients with chronic, stable HFpEF were enrolled. Outcomes were analyzed by core laboratories blinded to treatment groups; however, the patients and staff conducting the evaluations were not blinded.

Interventions: Patients were randomly assigned (1:1:1; n = 60 per group) to high-intensity interval training (3 × 38 minutes/week), moderate continuous training (5 × 40 minutes/week), or guideline control (1-time advice on physical activity according to guidelines) for 12 months (3 months in clinic followed by 9 months telemedically supervised home-based exercise).

Main Outcomes And Measures: Primary end point was change in peak V̇o2 after 3 months, with the minimal clinically important difference set at 2.5 mL/kg/min. Secondary end points included changes in metrics of cardiorespiratory fitness, diastolic function, and natriuretic peptides after 3 and 12 months.

Results: Among 180 patients who were randomized (mean age, 70 years; 120 women [67%]), 166 (92%) and 154 (86%) completed evaluation at 3 and 12 months, respectively. Change in peak V̇o2 over 3 months for high-intensity interval training vs guideline control was 1.1 vs -0.6 mL/kg/min (difference, 1.5 [95% CI, 0.4 to 2.7]); for moderate continuous training vs guideline control, 1.6 vs -0.6 mL/kg/min (difference, 2.0 [95% CI, 0.9 to 3.1]); and for high-intensity interval training vs moderate continuous training, 1.1 vs 1.6 mL/kg/min (difference, -0.4 [95% CI, -1.4 to 0.6]). No comparisons were statistically significant after 12 months. There were no significant changes in diastolic function or natriuretic peptides. Acute coronary syndrome was recorded in 4 high-intensity interval training patients (7%), 3 moderate continuous training patients (5%), and 5 guideline control patients (8%).

Conclusions And Relevance: Among patients with HFpEF, there was no statistically significant difference in change in peak V̇o2 at 3 months between those assigned to high-intensity interval vs moderate continuous training, and neither group met the prespecified minimal clinically important difference compared with the guideline control. These findings do not support either high-intensity interval training or moderate continuous training compared with guideline-based physical activity for patients with HFpEF.

Trial Registration: ClinicalTrials.gov Identifier: NCT02078947.
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http://dx.doi.org/10.1001/jama.2020.26812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873782PMC
February 2021

Molecular Mechanisms of Diaphragm Myopathy in Humans With Severe Heart Failure.

Circ Res 2021 03 4;128(6):706-719. Epub 2021 Feb 4.

Department of Internal Medicine and Cardiology (N.M., E.B.W., J.H., C.S., A.L. V.A.), Herzzentrum Dresden, Technische Universität Dresden, Germany.

[Figure: see text].
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http://dx.doi.org/10.1161/CIRCRESAHA.120.318060DOI Listing
March 2021

Extracorporeal life support in patients with acute myocardial infarction complicated by cardiogenic shock - Design and rationale of the ECLS-SHOCK trial.

Am Heart J 2021 04 8;234:1-11. Epub 2021 Jan 8.

University Clinic Düsseldorf, Düsseldorf, Germany.

Background: In acute myocardial infarction complicated by cardiogenic shock the use of mechanical circulatory support devices remains controversial and data from randomized clinical trials are very limited. Extracorporeal life support (ECLS) - venoarterial extracorporeal membrane oxygenation - provides the strongest hemodynamic support in addition to oxygenation. However, despite increasing use it has not yet been properly investigated in randomized trials. Therefore, a prospective randomized adequately powered clinical trial is warranted.

Study Design: The ECLS-SHOCK trial is a 420-patient controlled, international, multicenter, randomized, open-label trial. It is designed to compare whether treatment with ECLS in addition to early revascularization with percutaneous coronary intervention or alternatively coronary artery bypass grafting and optimal medical treatment is beneficial in comparison to no-ECLS in patients with severe infarct-related cardiogenic shock. Patients will be randomized in a 1:1 fashion to one of the two treatment arms. The primary efficacy endpoint of ECLS-SHOCK is 30-day mortality. Secondary outcome measures such as hemodynamic, laboratory, and clinical parameters will serve as surrogate endpoints for prognosis. Furthermore, a longer follow-up at 6 and 12 months will be performed including quality of life assessment. Safety endpoints include peripheral ischemic vascular complications, bleeding and stroke.

Conclusions: The ECLS-SHOCK trial will address essential questions of efficacy and safety of ECLS in addition to early revascularization in acute myocardial infarction complicated by cardiogenic shock.
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http://dx.doi.org/10.1016/j.ahj.2021.01.002DOI Listing
April 2021

Safety and Efficacy of Transcatheter Aortic Valve Replacement With Continuation of Vitamin K Antagonists or Direct Oral Anticoagulants.

JACC Cardiovasc Interv 2021 01 23;14(2):135-144. Epub 2020 Dec 23.

Heart Center Lucerne, Luzerner Kantonsspital, Lucerne, Switzerland. Electronic address:

Objectives: This study investigated whether transcatheter aortic valve replacement (TAVR) with peri-procedural continuation of oral anticoagulation is equally safe and efficacious as TAVR with peri-procedural interruption of anticoagulation.

Background: A significant proportion of patients undergoing TAVR have an indication for long-term oral anticoagulation. The optimal peri-procedural management of such patients is unknown.

Methods: Consecutive patients on oral anticoagulation who underwent transfemoral TAVR at 5 European centers were enrolled. Oral anticoagulation was either stopped 2 to 4 days before TAVR or continued throughout the procedure. Primary safety outcome was major bleeding. Secondary efficacy endpoints included vascular complications, stroke, and mortality.

Results: Of 4,459 patients, 584 patients were treated with continuation of anticoagulation and 733 with interruption of anticoagulation. At 30 days, major or life-threatening bleedings occurred in 66 (11.3%) versus 105 (14.3%; odds ratio [OR]: 0.86; 95% confidence interval [CI]: 0.61 to 1.21; p = 0.39) and major vascular complications in 64 (11.0%) versus 90 (12.3%; OR: 0.89; CI: 0.62 to 1.27; p = 0.52) of patients with continuation and with interruption of anticoagulation, respectively. Transfusion of packed red blood cells was less often required in patients with continuation of anticoagulation (80 [13.7%] vs. 130 [17.7%]; OR: 0.59; 95% CI: 0.42 to 0.81; p = 0.001). Kaplan-Meier estimates of survival at 12 months were 85.3% in patients with continuation of anticoagulation and 84.0% in patients with interruption of anticoagulation (hazard ratio: 0.90; 95% CI: 0.73 to 1.12; p = 0.36).

Conclusions: Continuation of oral anticoagulation throughout TAVR did not increase bleeding or vascular complication rates. Moreover, packed red blood cell transfusions were less often required in patients with continuation of oral anticoagulation.
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http://dx.doi.org/10.1016/j.jcin.2020.09.062DOI Listing
January 2021

Muscular changes in animal models of heart failure with preserved ejection fraction: what comes closest to the patient?

ESC Heart Fail 2021 02 17;8(1):139-150. Epub 2020 Dec 17.

Laboratory for Experimental and Molecular Cardiology, Department of Internal Medicine and Cardiology, TU Dresden, Heart Center Dresden University Hospital, Fetscherstrasse 76, Dresden, 01307, Germany.

Aims: Heart failure with preserved ejection fraction (HFpEF) is associated with reduced exercise capacity elicited by skeletal muscle (SM) alterations. Up to now, no clear medical treatment advice for HFpEF is available. Identification of the ideal animal model mimicking the human condition is a critical step in developing and testing treatment strategies. Several HFpEF animals have been described, but the most suitable in terms of comparability with SM alterations in HFpEF patients is unclear. The aim of the present study was to investigate molecular changes in SM of three different animal models and to compare them with alterations of muscle biopsies obtained from human HFpEF patients.

Methods And Results: Skeletal muscle tissue was obtained from HFpEF and control patients and from three different animal models including the respective controls-ZSF1 rat, Dahl salt-sensitive rat, and transverse aortic constriction surgery/deoxycorticosterone mouse. The development of HFpEF was verified by echocardiography. Protein expression and enzyme activity of selected markers were assessed in SM tissue homogenates. Protein expression between SM tissue obtained from HFpEF patients and the ZSF1 rats revealed similarities for protein markers involved in muscle atrophy (MuRF1 expression, protein ubiquitinylation, and LC3) and mitochondrial metabolism (succinate dehydrogenase and malate dehydrogenase activity, porin expression). The other two animal models exhibited far less similarities to the human samples.

Conclusions: None of the three tested animal models mimics the condition in HFpEF patients completely, but among the animal models tested, the ZSF1 rat (ZSF1-lean vs. ZSF1-obese) shows the highest overlap to the human condition. Therefore, when studying therapeutic interventions to treat HFpEF and especially alterations in the SM, we suggest that the ZSF1 rat is a suitable model.
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http://dx.doi.org/10.1002/ehf2.13142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835579PMC
February 2021

Paraneoplastic Syndrome and SARS-CoV-2-Incremental Effect of 2 Thrombogenic Conditions?

CJC Open 2021 Feb 21;3(2):217-220. Epub 2020 Oct 21.

Herzzentrum Dresden, Technische Universität Dresden, Department of Internal Medicine and Cardiology, Dresden, Germany.

We present the case of a patient with a nonbacterial thrombotic aortic valve endocarditis experiencing severe thromboembolic complications and an acute right internal carotid artery occlusion in the context of a paraneoplastic syndrome and an asymptomatic severe acute respiratory syndrome coronavirus-2 infection, despite treatment with different and overlapping anticoagulant medications. Patients with increased thrombogenicity due to an underlying disease might be at increased risk for thrombotic events during a severe acute respiratory syndrome coronavirus-2 infection.
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http://dx.doi.org/10.1016/j.cjco.2020.10.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577269PMC
February 2021

Influence of decompensated heart failure on cardiac acoustic biomarkers: impact on early readmissions.

ESC Heart Fail 2020 Oct 16. Epub 2020 Oct 16.

Division of Cardiology, Medical University of Graz, Auenbruggerplatz 15, Graz, 8036, Austria.

Aims: Preventing hospitalization by detecting early evidence of heart failure (HF) decompensation in an outpatient setting can improve patient's quality of life and reduce costs of care. The purpose of this study was to assess the value of cardiac acoustic biomarkers (CABs), a combination of cardiohaemic vibrations synchronized with ECG signals, and heart rate (HR) for detecting HF decompensation during first 3 months after hospital discharge for HF.

Methods And Results: Patients with an ejection fraction ≤35% (HFrEF) and hospitalized for decompensated HF were enrolled in a prospective observational study. All subjects wore a wearable cardioverter-defibrillator (ZOLL LifeVest , Pittsburgh, PA, USA) that is capable of recording CABs and HR. The primary endpoint of the study was the first HF event, defined as HF readmission or HF emergency room visit. From June 2017 through August 2019, 671 patients with HFrEF were enrolled. Eighty-one patients (12.1%) had a total of 112 HF events. The algorithm detected HF events with a median of 32 days (interquartile range = 11-45) in advance of the first HF event. The algorithm had a sensitivity of 69%, specificity of 60%, positive predictive value of 19%, and a negative predictive value of 94%. Of note, the baseline (first 7 days post-enrolment) algorithm using CABs and HR was superior to New York Heart Association classification in detecting patients more likely to have HF decompensation (sensitivity and specificity of 61% and 68% vs. 46% and 55%, respectively).

Conclusions: This prospective international registry showed that an algorithm incorporating CABs and HR data detected HF events 30 days in advance of the event in patients with HFrEF during first 3 months after hospital discharge. Therefore, integrating CAB technology into clinical practice may prevent HF rehospitalizations.
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http://dx.doi.org/10.1002/ehf2.13045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754974PMC
October 2020

Small-Molecule Chemical Knockdown of MuRF1 in Melanoma Bearing Mice Attenuates Tumor Cachexia Associated Myopathy.

Cells 2020 10 11;9(10). Epub 2020 Oct 11.

Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany.

Patients with malignant tumors frequently suffer during disease progression from a syndrome referred to as cancer cachexia (CaCax): CaCax includes skeletal muscle atrophy and weakness, loss of bodyweight, and fat tissues. Currently, there are no FDA (Food and Drug Administration) approved treatments available for CaCax. Here, we studied skeletal muscle atrophy and dysfunction in a murine CaCax model by injecting B16F10 melanoma cells into mouse thighs and followed mice during melanoma outgrowth. Skeletal muscles developed progressive weakness as detected by wire hang tests (WHTs) during days 13-23. Individual muscles analyzed at day 24 had atrophy, mitochondrial dysfunction, augmented metabolic reactive oxygen species (ROS) stress, and a catabolically activated ubiquitin proteasome system (UPS), including upregulated MuRF1. Accordingly, we tested as an experimental intervention of recently identified small molecules, Myomed-205 and -946, that inhibit MuRF1 activity and MuRF1/MuRF2 expression. Results indicate that MuRF1 inhibitor fed attenuated induction of MuRF1 in tumor stressed muscles. In addition, the compounds augmented muscle performance in WHTs and attenuated muscle weight loss. Myomed-205 and -946 also rescued citrate synthase and complex-1 activities in tumor-stressed muscles, possibly suggesting that mitochondrial-metabolic and muscle wasting effects in this CaCax model are mechanistically connected. Inhibition of MuRF1 during tumor cachexia may represent a suitable strategy to attenuate skeletal muscle atrophy and dysfunction.
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http://dx.doi.org/10.3390/cells9102272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600862PMC
October 2020

Percutaneous Left Ventricular Assist Device Leads to Heart Rhythm Stabilisation in Cardiogenic Shock: Results from the Dresden Impella Registry.

Heart Lung Circ 2021 Apr 7;30(4):577-584. Epub 2020 Oct 7.

Klinikum Chemnitz, Klinik für Innere Medizin I, Chemnitz, Germany.

Background: Severe heart rhythm disturbances (SHRDs) occur regularly in cardiogenic shock (CS). Percutaneous left ventricular assist devices (pLVADs) can actively unload the left ventricle (LV), decreasing left ventricular end-diastolic pressure and wall tension, which are suspected parameters for the induction and maintenance of arrhythmias. The aim of this study was to describe effects of LV unloading on SHRD.

Method: In the Dresden Impella Registry, 97 patients received an Impella CP in refractory CS. Of them, 19 had SHRDs, which were not stopped by common therapeutic strategies such as electrical defibrillation or antiarrhythmic drugs. They were only stopped after implantation of a micro-axial heart pump. This phenomenon was referred to as heart rhythm stabilisation (HRS). Clinical outcome and laboratory parameters were assessed and risk factors for the occurrence of HRS were identified.

Results: All 19 patients with refractory SHRD terminated immediately into a stable heart rhythm after insertion of the micro-axial heart pump. In 37% no additional defibrillation was needed. Of the patients with HRS, CS was mostly caused by myocardial infarction (68%). Resuscitation before pLVAD was performed in 89% for more than 30 minutes. Patients with HRS were resuscitated more frequently and for a longer duration than patients without HRS. After HRS, the serum lactate and norepinephrine dosage decreased in the first 12 hours, whereas left ventricular ejection fraction increased by 95%.

Conclusions: Left ventricular unloading in patients with CS seems to be an option for treating patients with sustained life-threatening tachycardia, who are refractory to common treatment.
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http://dx.doi.org/10.1016/j.hlc.2020.08.005DOI Listing
April 2021
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