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1. Adipose tissue ATGL modifies the cardiac lipidome in pressure-overload-induced left ventricular failure.

Author: Janek Salatzki, Anna Foryst-Ludwig, Kajetan Bentele, Annelie Blumrich, Elia Smeir, Zsofia Ban, Sarah Brix, Jana Grune, Niklas Beyhoff, Robert Klopfleisch, Sebastian Dunst, Michal A Surma, Christian Klose, Michael Rothe, Frank R Heinzel, Alexander Krannich, Erin E Kershaw, Dieter Beule, P Christian Schulze, Nikolaus Marx, and Ulrich Kintscher
Subjects: Genetics, QH426-470
Abstract: Adipose tissue lipolysis occurs during the development of heart failure as a consequence of chronic adrenergic stimulation. However, the impact of enhanced adipose triacylglycerol hydrolysis mediated by adipose triglyceride lipase (ATGL) on cardiac function is unclear. To investigate the role of adipose tissue lipolysis during heart failure, we generated mice with tissue-specific deletion of ATGL (atATGL-KO). atATGL-KO mice were subjected to transverse aortic constriction (TAC) to induce pressure-mediated cardiac failure. The cardiac mouse lipidome and the human plasma lipidome from healthy controls (n = 10) and patients with systolic heart failure (HFrEF, n = 13) were analyzed by MS-based shotgun lipidomics. TAC-induced increases in left ventricular mass (LVM) and diastolic LV inner diameter were significantly attenuated in atATGL-KO mice compared to wild type (wt) -mice. More importantly, atATGL-KO mice were protected against TAC-induced systolic LV failure. Perturbation of lipolysis in the adipose tissue of atATGL-KO mice resulted in the prevention of the major cardiac lipidome changes observed after TAC in wt-mice. Profound changes occurred in the lipid class of phosphatidylethanolamines (PE) in which multiple PE-species were markedly induced in failing wt-hearts, which was attenuated in atATGL-KO hearts. Moreover, selected heart failure-induced PE species in mouse hearts were also induced in plasma samples from patients with chronic heart failure. TAC-induced cardiac PE induction resulted in decreased PC/ PE-species ratios associated with increased apoptotic marker expression in failing wt-hearts, a process absent in atATGL-KO hearts. Perturbation of adipose tissue lipolysis by ATGL-deficiency ameliorated pressure-induced heart failure and the potentially deleterious cardiac lipidome changes that accompany this pathological process, namely the induction of specific PE species. Non-cardiac ATGL-mediated modulation of the cardiac lipidome may play an important role in the pathogenesis of chronic heart failure.
Published: 2018
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2. Blood-based microRNA profiling in patients with cardiac amyloidosis.

Author: Anselm A Derda, Angelika Pfanne, Christian Bär, Katharina Schimmel, Peter J Kennel, Ke Xiao, P Christian Schulze, Johann Bauersachs, and Thomas Thum
Subjects: Medicine, Science
Abstract: INTRODUCTION:Amyloidosis is caused by dysregulation of protein folding resulting in systemic or organ specific amyloid aggregation. When affecting the heart, amyloidosis can cause severe heart failure, which is associated with a high morbidity and mortality. Different subtypes of cardiac amyloidosis exist e.g. transthyretin cardiac amyloidosis and senile cardiac amyloidosis. Today, diagnostics is primarily based on cardiac biopsies and no clinically used circulating blood-based biomarkers existing. Therefore, our aim was to identify circulating microRNAs in patients with different forms of amyloidosis. METHODS:Blood was collected from healthy subjects (n = 10), patients with reduced ejection fraction (EF < 35%; n = 10), patients affected by transthyretin cardiac amyloidosis (n = 13) as well as senile cardiac amyloidosis (n = 11). After performing TaqMan array profiling, promising candidates, in particular miR-99a-5p, miR-122-5p, miR-27a-3p, miR-221-3p, miR-1180-3p, miR-155-5p, miR-339-3p, miR-574-3p, miR-342-3p and miR-329-3p were validated via quantitative real time PCR. RESULTS:The validation experiments revealed a significant upregulation of miR-339-3p in patients affected with senile cardiac amyloidosis compared to controls. This corresponded to the array profiling results. In contrast, there was no deregulation in the other patient groups. CONCLUSION:MiR-339-3p was increased in blood of patients with senile cardiac amyloidosis. Therefore, miR-339-3p is a potential candidate as biomarker for senile cardiac amyloidosis in future studies. Larger patient cohorts should be investigated.
Published: 2018
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3. Correlation of high-resolution computed tomography and immunological bronchoalveolar lavage in interstitial lung disease at the onset of inflammatory rheumatic diseases: implications for diagnosis and therapeutic strategies

Author: Tobias Hoffmann, Ulf Teichgräber, Martin Förster, Peter Oelzner, Claus Kroegel, Diane Renz, Tobias Weise, Joachim Böttcher, P. Christian Schulze, Gunter Wolf, Marcus Franz, and Alexander Pfeil
Subjects: Diseases of the musculoskeletal system, RC925-935
Abstract: Abstract Objectives Inflammatory rheumatic diseases (IRD) are often associated with interstitial lung disease (ILD). The aim of the present study was to establish a correlation between the findings on HRCT and the immunological bronchoalveolar lavage (BAL). Methods The study included 74 patients with newly diagnosed IRD and evidence of ILD on HRCT with the following pattern: ground-glass opacities (GGO), non-specific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP). Patients with other HRCT pattern were excluded. No patient received any immunosuppressive therapy. In addition to HRCT, immunological BAL was performed and the American Thoracic Society clinical practice guideline were used to define BAL patterns (lymphocytic cellular pattern, neutrophilic cellular pattern, eosinophilic cellular pattern and unspecified pattern). Results The main HRCT patterns were NSIP (47.3%), GGO (33.8%), and UIP (18.9%). BAL patterns showed the following distribution: 41.9% lymphocytic cellular pattern, 23.0% neutrophilic cellular pattern, 18.9% eosinophilic cellular pattern, and 16.2% unspecific cellular pattern. Placing these data in the context of the HRCT findings, the lymphocytic cellular BAL pattern (48%) was most commonly BAL pattern associated with GGO pattern in HRCT, whereas neutrophilic and lymphocytic cellular BAL patterns were the dominant feature in NSIP and UIP. Conclusion In patients with new-onset IRD and ILD, inflammatory pulmonary changes are predominate, reflected by GGO on HRCT and a mainly lymphocytic cell profile in the immunological BAL. In NSIP or UIP on HRCT, the percentages of lymphocytes and neutrophils were higher in BAL fluid, representing a fibrotic component in addition to the inflammation. Consequently, patients with evidence of GGO on HRCT should primarily be treated with anti-inflammatory/immunosuppressive therapy, whereas in patients with NSIP and UIP a combination of anti-inflammatory and anti-fibrotic agents would be the appropriate treatment.
Published: 2024
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4. Monogenic hypertriglyceridemia and recurrent pancreatitis in a homozygous carrier of a rare APOA5 mutation: a case report

Author: Umidakhon Makhmudova, P. Christian Schulze, Stefan Lorkowski, Winfried März, J.-A. Geiling, and Oliver Weingärtner
Subjects: Monogenic hypertriglyceridemia, APOA5, Acute pancreatitis, Volanesorsen, Case report, Medicine
Abstract: Abstract Background Homozygous mutations in the APOA5 gene constitute a rare cause of monogenic hypertriglyceridemia, or familial chylomicronemia syndrome (FCS). We searched PubMed and identified 16 cases of homozygous mutations in the APOA5 gene. Severe hypertriglyceridemia related to monogenic mutations in triglyceride-regulating genes can cause recurrent acute pancreatitis. Standard therapeutic approaches for managing this condition typically include dietary interventions, fibrates, and omega-3-fatty acids. A novel therapeutic approach, antisense oligonucleotide volanesorsen is approved for use in patients with FCS. Case presentation We report a case of a 25-years old Afghani male presenting with acute pancreatitis due to severe hypertriglyceridemia up to 29.8 mmol/L caused by homozygosity in APOA5 (c.427delC, p.Arg143Alafs*57). A low-fat diet enriched with medium-chain TG (MCT) oil and fibrate therapy did not prevent recurrent relapses, and volanesorsen was initiated. Volanesorsen resulted in almost normalized triglyceride levels. No further relapses of acute pancreatitis occurred. Patient reported an improve life quality due to alleviated chronic abdominal pain and headaches. Conclusions Our case reports a rare yet potentially life-threatening condition—monogenic hypertriglyceridemia-induced acute pancreatitis. The implementation of the antisense drug volanesorsen resulted in improved triglyceride levels, alleviated symptoms, and enhanced the quality of life.
Published: 2024
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5. Management of myocardial infarction with non-obstructive coronary arteries (MINOCA) in Germany: a single-center study on hospital resources and healthcare economics

Author: Franz Haertel, Carolin Montag, Thomas Kraeplin, Bernward Lauer, Nedim Memisevic, Sven Moebius-Winkler, P. Christian Schulze, and Sylvia Otto
Subjects: MINOCA, hospital resources, ACS, high care monitoring, intensive care, intermediate care, Public aspects of medicine, RA1-1270
Abstract: BackgroundPatients with myocardial infarction with non-obstructive coronary arteries (MINOCA) present as a main feature ≤50% stenosis upon angiography despite clinical symptoms and biomarker elevation related to acute coronary syndrome. Due to broad availability of high sensitivity troponin testing as well as invasive and non-invasive imaging, this clinical entity receives increasing clinical awareness.ObjectiveWe aimed to investigate the in-hospital work flow and economic impact of MINOCA vs. MICAD (myocardial infarction with obstructive coronary artery disease) patients and related clinical outcomes in a single-center patient collective of a large university heart center in Germany.MethodsWe retrospectively screened and analyzed all patients who were admitted to our hospital under the suspicion of an acute coronary syndrome within a 12-month period (2017–2018) for further diagnostics and treatment. All included patients showed a pathological troponin elevation and received invasive coronary angiography for acute coronary syndrome. Associated in-hospital costs, procedural and various clinical parameters as well as timelines and parameters of work-flow were obtained.ResultsAfter screening of 3,021 patients, we included 660 patients with acute coronary syndrome. Of those, 118 patients were attributed to the MINOCA-group. 542 patients presented with a “classical” myocardial infarction (MICAD group). MINOCA patients were less frail, more likely female, but showed no relevant difference in age or other selected comorbidities except for fewer cases of diabetes. In-hospital mortality (11% vs. 0%; p
Published: 2024
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6. TXNIP regulates peripheral glucose metabolism in humans.

Author: Hemang Parikh, Emma Carlsson, William A Chutkow, Lovisa E Johansson, Heidi Storgaard, Pernille Poulsen, Richa Saxena, Christine Ladd, P Christian Schulze, Michael J Mazzini, Christine Bjørn Jensen, Anna Krook, Marie Björnholm, Hans Tornqvist, Juleen R Zierath, Martin Ridderstråle, David Altshuler, Richard T Lee, Allan Vaag, Leif C Groop, and Vamsi K Mootha
Subjects: Medicine
Abstract: BackgroundType 2 diabetes mellitus (T2DM) is characterized by defects in insulin secretion and action. Impaired glucose uptake in skeletal muscle is believed to be one of the earliest features in the natural history of T2DM, although underlying mechanisms remain obscure.Methods and findingsWe combined human insulin/glucose clamp physiological studies with genome-wide expression profiling to identify thioredoxin interacting protein (TXNIP) as a gene whose expression is powerfully suppressed by insulin yet stimulated by glucose. In healthy individuals, its expression was inversely correlated to total body measures of glucose uptake. Forced expression of TXNIP in cultured adipocytes significantly reduced glucose uptake, while silencing with RNA interference in adipocytes and in skeletal muscle enhanced glucose uptake, confirming that the gene product is also a regulator of glucose uptake. TXNIP expression is consistently elevated in the muscle of prediabetics and diabetics, although in a panel of 4,450 Scandinavian individuals, we found no evidence for association between common genetic variation in the TXNIP gene and T2DM.ConclusionsTXNIP regulates both insulin-dependent and insulin-independent pathways of glucose uptake in human skeletal muscle. Combined with recent studies that have implicated TXNIP in pancreatic beta-cell glucose toxicity, our data suggest that TXNIP might play a key role in defective glucose homeostasis preceding overt T2DM.
Published: 2007
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7. Expression of Inflammatory Genes in Murine Lungs in a Model of Experimental Pulmonary Hypertension: Effects of an Antibody-Based Targeted Delivery of Interleukin-9

Author: Judith Heiss, Katja Grün, Isabell Singerer, Laura Tempel, Mattia Matasci, Christian Jung, Alexander Pfeil, P. Christian Schulze, Dario Neri, and Marcus Franz
Subjects: drug delivery, inflammation, gene expression analysis, pulmonary hypertension, Diseases of the respiratory system, RC705-779, Medicine (General), R5-920
Abstract: Background: Pathogenesis of pulmonary hypertension (PH) is a multifactorial process driven by inflammation and pulmonary vascular remodeling. To target these two aspects of PH, we recently tested a novel treatment: Interleukin-9 (IL9) fused to F8, an antibody that binds to the extra-domain A of fibronectin (EDA+ Fn). As EDA+ Fn is not found in healthy adult tissue but is expressed during PH, IL9 is delivered specifically to the tissue affected by PH. We found that F8IL9 reduced pulmonary vascular remodeling and attenuated PH compared with sham-treated mice. Purpose: To evaluate possible F8IL9 effects on PH-associated inflammatory processes, we analysed the expression of genes involved in pulmonary immune responses. Methods: We applied the monocrotaline (MCT) model of PH in mice (n = 44). Animals were divided into five experimental groups: sham-induced animals without PH (control, n = 4), MCT-induced PH without treatment (PH, n = 8), dual endothelin receptor antagonist treatment (dual ERA, n = 8), F8IL9 treatment (n = 12, 2 formats with n = 6 each), or with KSFIL9 treatment (KSFIL9, n = 12, 2 formats with n = 6 each, KSF: control antibody with irrelevant antigen specificity). After 28 days, a RT-PCR gene expression analysis of inflammatory response (84 genes) was performed in the lung. Results: Compared with the controls, 19 genes exhibited relevant (+2.5-fold) upregulation in the PH group without treatment. Gene expression levels in F8IL9-treated lung tissue were reduced compared to the PH group without treatment. This was the case especially for CCL20, CXCL5, C-reactive protein, pentraxin related (CRPPR), and Kininogen-1 (KNG1). Conclusion: In accordance with the hypothesis stated above, F8IL9 treatment diminished the upregulation of some genes associated with inflammation in a PH animal model. Therefore, we hypothesize that IL9-based immunocytokine treatment will likely modulate various inflammatory pathways.
Published: 2024
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8. Determination of brain death using 99mTc-HMPAO scintigraphy and transcranial duplex sonography in a patient on veno-arterial ECMO

Author: Albrecht Günther, Anke Werner, Michael Fritzenwanger, Martin Brauer, Martin Freesmeyer, P. Christian Schulze, Farid Salih, and Robert Drescher
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Published: 2024
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9. Use of Autotransfusion following Percutaneous Thrombectomy for Cardiogenic Shock Due to Pulmonary Embolism in a Single Session—A Case Report

Author: Franz Haertel, Laura Baez, Marcus Franz, Jurgen Bogoviku, Friederike Klein, Gudrun Dannberg, P. Christian Schulze, and Sven Möbius-Winkler
Subjects: pulmonary embolism, shock, acute heart failure, percutaneous mechanical thrombectomy, autotransfusion, Medicine (General), R5-920
Abstract: A 64-year-old male patient was admitted to the catheterization laboratory with a suspected myocardial infarction and in cardiogenic shock. Upon further investigation, a massive bilateral pulmonary embolism with signs of right heart dysfunction was discovered, leading to a decision to perform a direct interventional treatment with a thrombectomy device for thrombus aspiration. The procedure was successful in removing almost the entirety of the thrombotic material from the pulmonary arteries. The patient’s hemodynamics stabilized and oxygenation improved instantly. The procedure required a total of 18 aspiration cycles. Each aspiration contained approx. 60 mL blood amounting to a total of approx. 1080 mL of blood. During the procedure, a mechanical blood salvage system was used to resupply 50% of the blood via autotransfusion that would otherwise have been lost. The patient was transferred to the intensive care unit for post-interventional care and monitoring. A CT angiography of the pulmonary arteries after the procedure confirmed the presence of only minor residual thrombotic material. The patient’s clinical, ECG, echocardiographic, and laboratory parameters returned to normal or near normal ranges. The patient was discharged shortly after in stable conditions on oral anticoagulation.
Published: 2023
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10. Cardiac Metabolism in Heart Failure and Implications for Uremic Cardiomyopathy

Author: T. Dung Nguyen and P. Christian Schulze
Subjects: Physiology, Cardiology and Cardiovascular Medicine
Abstract: Chronic kidney disease is associated with an increased risk for the development and progression of cardiovascular disorders including hypertension, dyslipidemia, and coronary artery disease. Chronic kidney disease may also affect the myocardium through complex systemic changes, resulting in structural remodeling such as hypertrophy and fibrosis, as well as impairments in both diastolic and systolic function. These cardiac changes in the setting of chronic kidney disease define a specific cardiomyopathic phenotype known as uremic cardiomyopathy. Cardiac function is tightly linked to its metabolism, and research over the past 3 decades has revealed significant metabolic remodeling in the myocardium during the development of heart failure. Because the concept of uremic cardiomyopathy has only been recognized in recent years, there are limited data on metabolism in the uremic heart. Nonetheless, recent findings suggest overlapping mechanisms with heart failure. This work reviews key features of metabolic remodeling in the failing heart in the general population and extends this to patients with chronic kidney disease. The knowledge of similarities and differences in cardiac metabolism between heart failure and uremic cardiomyopathy may help identify new targets for mechanistic and therapeutic research on uremic cardiomyopathy.
Published: 2023
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11. Timing of Active Left Ventricular Unloading in Patients on Venoarterial Extracorporeal Membrane Oxygenation Therapy

Author: Benedikt Schrage, Jonas Sundermeyer, Stefan Blankenberg, Pascal Colson, Dennis Eckner, Matthias Eden, Ingo Eitel, Derk Frank, Norbert Frey, Tobias Graf, Paulus Kirchhof, Danny Kupka, Ulf Landmesser, Axel Linke, Nicolas Majunke, Norman Mangner, Octavian Maniuc, Johannes Mierke, Sven Möbius-Winkler, David A. Morrow, Marc Mourad, Peter Nordbeck, Martin Orban, Federico Pappalardo, Sandeep M. Patel, Matthias Pauschinger, Vittorio Pazzanese, Darko Radakovic, P. Christian Schulze, Clemens Scherer, Robert H.G. Schwinger, Carsten Skurk, Holger Thiele, Anubodh Varshney, Lukas Wechsler, and Dirk Westermann
Subjects: Cardiology and Cardiovascular Medicine
Published: 2023
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12. Erhalt von Leistungsfähigkeit und Lebensqualität bei chronischer Herzinsuffizienz (Teil 3)

Author: Stephan von Haehling, Michael Arzt, Wolfram Doehner, Frank Edelmann, Ruben Evertz, Nicole Ebner, Christoph Herrmann-Lingen, Tania Garfias-Veitl, Michael Koziolek, Michel Noutsias, P. Christian Schulze, Rolf Wachter, Gerd Hasenfuß, and Ulrich Laufs
Published: 2023
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13. Survival After Invasive or Conservative Management of Stable Coronary Disease

Author: Judith S. Hochman, Rebecca Anthopolos, Harmony R. Reynolds, Sripal Bangalore, Yifan Xu, Sean M. O’Brien, Stavroula Mavromichalis, Michelle Chang, Aira Contreras, Yves Rosenberg, Ruth Kirby, Balram Bhargava, Roxy Senior, Ann Banfield, Shaun G. Goodman, Renato D. Lopes, Radosław Pracoń, José López-Sendón, Aldo Pietro Maggioni, Jonathan D. Newman, Jeffrey S. Berger, Mandeep S. Sidhu, Harvey D. White, Andrea B. Troxel, Robert A. Harrington, William E. Boden, Gregg W. Stone, Daniel B. Mark, John A. Spertus, David J. Maron, Shari Esquenazi-Karonika, Margaret Gilsenan, Ewelina Gwiszcz, Patenne Mathews, Samaa Mohamed, Anna Naumova, Arline Roberts, Kerrie VanLoo, Ying Lu, Zhen Huang, Samuel Broderick, Luis Guzmán, Joseph Selvanayagam, Gabriel Steg, Jean-Michel Juliard, Rolf Doerr, Matyas Keltai, Boban Thomas, Tali Sharir, Eugenia Nikolsky, Aldo P. Maggioni, Shun Kohsaka, Jorge Escobedo, Olga Bockeria, Claes Held, Leslee J. Shaw, Lawrence Phillips, Daniel Berman, Raymond Y. Kwong, Michael H. Picard, Bernard R. Chaitman, Ziad Ali, James Min, G.B. John Mancini, Jonathon Leipsic, Graham Hillis, Suku Thambar, Majo Joseph, John Beltrame, Irene Lang, Herwig Schuchlenz, Kurt Huber, Kaatje Goetschalckx, Whady Hueb, Paulo Ricardo Caramori, Alexandre de Quadros, Paola Smanio, Claudio Mesquita, João Vitola, José Marin-Neto, Expedito Ribeiro da Silva, Rogério Tumelero, Marianna Andrade, Alvaro Rabelo Alves, Frederico Dall’Orto, Carisi Polanczyk, Estevão Figueiredo, Andrew Howarth, Gilbert Gosselin, Asim Cheema, Kevin Bainey, Denis Phaneuf, Ariel Diaz, Pallav Garg, Shamir Mehta, Graham Wong, Andy Lam, James Cha, Paul Galiwango, Amar Uxa, Benjamin (Ben) Chow, Adnan Hameed, Jacob Udell, Magdy Hamid, Marie Hauguel-Moreau, Alain Furber, Pascal Goube, Philippe-Gabriel Steg, Gilles Barone-Rochette, Christophe Thuaire, Michel Slama, Georg Nickenig, Raffi Bekeredjian, P. Christian Schulze, Bela Merkely, Geza Fontos, András Vértes, Albert Varga, Ajit Kumar, Rajesh G. Nair, Purvez Grant, Cholenahally Manjunath, Nagaraja Moorthy, Santhosh Satheesh, Ranjit Kumar Nath, Gurpreet Wander, Johann Christopher, Sudhanshu Dwivedi, Abraham Oomman, Atul Mathur, Milind Gadkari, Sudhir Naik, Eapen Punnoose, Ranjan Kachru, Upendra Kaul, Arthur Kerner, Giuseppe Tarantini, Gian Piero Perna, Emanuela Racca, Andrea Mortara, Lorenzo Monti, Carlo Briguori, Gianpiero Leone, Roberto Amati, Mauro Salvatori, Antonio Di Chiara, Paolo Calabro, Marcello Galvani, Stefano Provasoli, Keiichi Fukuda, Shintaro Nakano, Aleksandras Laucevicius, Sasko Kedev, Ahmad Khairuddin, Robert Riezebos, Jorik Timmer, Spencer Heald, Ralph Stewart, Walter Mogrovejo Ramos, Marcin Demkow, Tomasz Mazurek, Jarozlaw Drozdz, Hanna Szwed, Adam Witkowski, Nuno Ferreira, Fausto Pinto, Ruben Ramos, Bogdan Popescu, Calin Pop, Leo Bockeria, Elena Demchenko, Alexander Romanov, Leonid Bershtein, Ahmed Jizeeri, Goran Stankovic, Svetlana Apostolovic, Nada Cemerlic Adjic, Marija Zdravkovic, Branko Beleslin, Milica Dekleva, Goran Davidovic, Terrance Chua, David Foo, Kian Keong Poh, Mpiko Ntsekhe, Alessandro Sionis, Francisco Marin, Vicente Miró, Montserrat Gracida Blancas, José González-Juanatey, Francisco Fernández-Avilés, Jesús Peteiro, Jose Enrique Castillo Luena, Johannes Aspberg, Mariagrazia Rossi, Srun Kuanprasert, Sukit Yamwong, Nicola Johnston, Patrick Donnelly, Andrew Moriarty, Ahmed Elghamaz, Sothinathan Gurunathan, Nikolaos Karogiannis, Benoy N. Shah, Richard H.J. Trimlett, Michael B. Rubens, Edward D. Nicol, Tarun K. Mittal, Reinette Hampson, Reto Gamma, Mark De Belder, Thuraia Nageh, Steven Lindsay, Kreton Mavromatis, Todd Miller, Subhash Banerjee, Harmony Reynolds, Khaled Nour, and Peter Stone
Subjects: Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract: Background: The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) compared an initial invasive versus an initial conservative management strategy for patients with chronic coronary disease and moderate or severe ischemia, with no major difference in most outcomes during a median of 3.2 years. Extended follow-up for mortality is ongoing. Methods: ISCHEMIA participants were randomized to an initial invasive strategy added to guideline-directed medical therapy or a conservative strategy. Patients with moderate or severe ischemia, ejection fraction ≥35%, and no recent acute coronary syndromes were included. Those with an unacceptable level of angina were excluded. Extended follow-up for vital status is being conducted by sites or through central death index search. Data obtained through December 2021 are included in this interim report. We analyzed all-cause, cardiovascular, and noncardiovascular mortality by randomized strategy, using nonparametric cumulative incidence estimators, Cox regression models, and Bayesian methods. Undetermined deaths were classified as cardiovascular as prespecified in the trial protocol. Results: Baseline characteristics for 5179 original ISCHEMIA trial participants included median age 65 years, 23% women, 16% Hispanic, 4% Black, 42% with diabetes, and median ejection fraction 0.60. A total of 557 deaths accrued during a median follow-up of 5.7 years, with 268 of these added in the extended follow-up phase. This included a total of 343 cardiovascular deaths, 192 noncardiovascular deaths, and 22 unclassified deaths. All-cause mortality was not different between randomized treatment groups (7-year rate, 12.7% in invasive strategy, 13.4% in conservative strategy; adjusted hazard ratio, 1.00 [95% CI, 0.85–1.18]). There was a lower 7-year rate cardiovascular mortality (6.4% versus 8.6%; adjusted hazard ratio, 0.78 [95% CI, 0.63–0.96]) with an initial invasive strategy but a higher 7-year rate of noncardiovascular mortality (5.6% versus 4.4%; adjusted hazard ratio, 1.44 [95% CI, 1.08–1.91]) compared with the conservative strategy. No heterogeneity of treatment effect was evident in prespecified subgroups, including multivessel coronary disease. Conclusions: There was no difference in all-cause mortality with an initial invasive strategy compared with an initial conservative strategy, but there was lower risk of cardiovascular mortality and higher risk of noncardiovascular mortality with an initial invasive strategy during a median follow-up of 5.7 years. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04894877.
Published: 2023
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14. A Comparative Analysis of Novel Biomarkers in Sepsis and Cardiovascular Disease

Author: Peter Jirak, Franz Haertel, Moritz Mirna, Richard Rezar, Michael Lichtenauer, Vera Paar, Lukas J. Motloch, Albert Topf, Atilla Yilmaz, Uta C. Hoppe, P. Christian Schulze, Sebastian Nuding, Karl Werdan, Daniel Kretzschmar, Rudin Pistulli, and Henning Ebelt
Subjects: biomarkers, sepsis, STEMI, heart failure, cardiovascular disease, ST2, Technology, Engineering (General). Civil engineering (General), TA1-2040, Biology (General), QH301-705.5, Physics, QC1-999, Chemistry, QD1-999
Abstract: (1) Background: Sepsis still represents a major health care challenge, with mortality rates exceeding 25% in the western world. To further improve outcomes in this patient collective, new cardiovascular biomarkers present a promising opportunity as they target the paramount prognostic processes in sepsis: inflammation and ischemia. However, in contrast to cardiovascular diseases, a detailed analysis of novel biomarkers in sepsis is still lacking. (2) Objective: In this project, we aimed to perform a comparative analysis of biomarker levels in ischemic cardiovascular disease and sepsis. Analyzed markers comprised soluble suppression of tumorigenicity 2 (sST2; hemodynamics and inflammation), growth-differentiation factor 15 (GDF-15; injury, remodelling), soluble urokinase-type plasminogen activator receptor (suPAR; inflammation and remodeling) and heart-type fatty acid binding protein (H-FABP; myocardial ischemia). (3) Methods: In total, 311 patients were included in the study: 123 heart-failure (HF) patients, 60 patients with ST-segment elevation myocardial infarction (STEMI) and 53 sepsis patients. A total of 75 patients without coronary artery disease or signs of heart failure served as a control group. Plasma samples were analyzed by use of ELISA after informed consent. (4) Results: Patients with sepsis showed significantly increased plasma levels in all tested biomarkers compared to cardiovascular disease entities (sST2, suPAR, GDF-15: p < 0.001; H-FABP: compared to HF p < 0.001) and controls (sST2: 7.4-fold, suPAR: 3.4-fold, GDF-15: 6.5-fold and H-FABP: 15.3-fold increased plasma levels, p < 0.001). Moreover, in patients with sepsis, serum concentrations of sST2 and suPAR were significantly elevated in patients with HF and patients with STEMI (sST2: HF: 1.6-fold increase and STEMI: 2.5-fold increase, p < 0.001; suPAR: HF: 1.4-fold increase, p < 0.001 and STEMI: 1.4-fold increase, p < 0.01), whereas plasma levels of GDF-15 and H-FABP were markedly elevated in patients with STEMI only (GDF-15: 1.6-fold increase, H-FABP: 6.4-fold increase, p < 0.001). (5) Conclusions: All tested novel cardiac biomarkers showed significantly elevated levels in sepsis patients. Interestingly, a secretion pattern similar to STEMI was observed with regards to sST2 and HFABP. Thus, by providing an assessment tool especially covering the cardiovascular component of the disease, novel biomarkers offer a promising tool in sepsis patients.
Published: 2022
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15. Human Induced Pluripotent Stem Cell as a Disease Modeling and Drug Development Platform—A Cardiac Perspective

Author: Mohamed M. Bekhite and P. Christian Schulze
Subjects: iPSC, cardiomyocytes, metabolic phenotype, genome-editing, disease modeling, drug testing, Cytology, QH573-671
Abstract: A comprehensive understanding of the pathophysiology and cellular responses to drugs in human heart disease is limited by species differences between humans and experimental animals. In addition, isolation of human cardiomyocytes (CMs) is complicated because cells obtained by biopsy do not proliferate to provide sufficient numbers of cells for preclinical studies in vitro. Interestingly, the discovery of human-induced pluripotent stem cell (hiPSC) has opened up the possibility of generating and studying heart disease in a culture dish. The combination of reprogramming and genome editing technologies to generate a broad spectrum of human heart diseases in vitro offers a great opportunity to elucidate gene function and mechanisms. However, to exploit the potential applications of hiPSC-derived-CMs for drug testing and studying adult-onset cardiac disease, a full functional characterization of maturation and metabolic traits is required. In this review, we focus on methods to reprogram somatic cells into hiPSC and the solutions for overcome immaturity of the hiPSC-derived-CMs to mimic the structure and physiological properties of the adult human CMs to accurately model disease and test drug safety. Finally, we discuss how to improve the culture, differentiation, and purification of CMs to obtain sufficient numbers of desired types of hiPSC-derived-CMs for disease modeling and drug development platform.
Published: 2021
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16. A Review on the Evolving Roles of MiRNA-Based Technologies in Diagnosing and Treating Heart Failure

Author: Peter J. Kennel and P. Christian Schulze
Subjects: MicroRNA, miRNA, cardiac biomarker, heart failure, antagomir, Cytology, QH573-671
Abstract: MiRNA-regulated processes are pivotal in cardiovascular homeostasis and disease. These short non-coding RNAs have ideal properties that could be utilized as potential biomarkers; moreover, their functions as post-transcriptional regulators of mRNA make them interesting therapeutic targets. In this review, we summarize the current state of miRNA-based biomarkers in a variety of diseases leading to heart failure, as well as provide an outlook on developing miRNA-based therapies in the heart failure field.
Published: 2021
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17. Analysis of Metabolic Markers in Patients with Chronic Heart Failure before and after LVAD Implantation

Author: Marion S. Hilse, Tom Kretzschmar, Rudin Pistulli, Marcus Franz, Tarek Bekfani, Daniela Haase, Sophie Neugebauer, Michael Kiehntopf, Jan F. Gummert, Hendrik Milting, and P. Christian Schulze
Subjects: DCM, ICM, LVAD, mass spectrometry, metabolomics, Microbiology, QR1-502
Abstract: Chronic heart failure (HF) is a clinical syndrome characterized by functional impairments of the myocardium. Metabolic and clinical changes develop with disease progression. In an advanced state, left ventricular assist devices (LVADs) are implanted for mechanical unloading. Our study aimed to assess the effects of LVAD implantation on the metabolic phenotypes and their potential to reverse the latter in patients with advanced HF. Plasma metabolites were analyzed by LC–MS/MS in 20 patients with ischemic cardiomyopathy (ICM), 20 patients with dilative cardiomyopathy (DCM), and 20 healthy controls. Samples were collected in HF patients before, 30 days after, and >100 days after LVAD implantation. Out of 188 measured metabolites, 63 were altered in HF. Only three metabolites returned to pre-LVAD concentrations 100 days after LVAD implantation. Pre-LVAD differences between DCM and ICM were mainly observed for amino acids and biogenic amines. This study shows a reversal of metabolite abnormalities in HF as a result of LVAD implantation. The etiology of the underlying disease plays an essential role in defining which specific metabolic parameter is altered in HF and reversed by LVAD implantation. Our findings provide a detailed insight into the disease pattern of ICM and DCM and the potential for reversibility of metabolic abnormalities in HF.
Published: 2021
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18. Intravascular Lithotripsy in Calcified Peripheral Lesions: Single-Center JEN-Experience

Author: Daniel Kretzschmar, Sven Möbius-Winkler, Marcus Thieme, Pawel Aftanski, Friederike Klein, and P. Christian Schulze
Subjects: Cardiology and Cardiovascular Medicine
Abstract: Peripheral artery disease (PAD) shows increasing need for revascularization therapy. Interventional success in calcified lesions is limited. Here, intravascular lithotripsy (IVL), modifying intimal and medial calcium, is a promising treatment approach. A single-center, prospective all-comers registry for patients undergoing peripheral IVL was established to examine treatment success in PAD with severe vessel calcification. Periprocedural safety events as well as short-term and intermediate follow-up clinical data were evaluated. Between December 2018 and January 2021 all consecutive patients receiving peripheral lithotripsy at our center were analyzed. Clinical and angiographic data were evaluated. Angiographic images were analyzed using a semiautomatic software for quantitative vessel analysis. Eighty-five lesions in 61 limbs were treated with IVL in 51 patients presenting with Rutherford classes 2 to 5. Most lesions (68%) were localized in the superficial femoral artery. Mean calcified lesion length was 102.5 mm (10–390 mm), with a median peripheral arterial calcium score of 3, indicating a highly calcified status. In 58% of the patients, IVL was used as a stand-alone therapy. IVL resulted in a mean acute luminal gain of 2.6 ± 0.9 mm, resulting in stenosis reduction by 42.1 ± 15%. Mean ankle brachial index (ABI) improved significantly from 0.6 to 0.8 (p
Published: 2022
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19. Effects of Early Empagliflozin Initiation on Diuresis and Kidney Function in Patients With Acute Decompensated Heart Failure (EMPAG-HF)

Author: P. Christian Schulze, Jürgen Bogoviku, Julian Westphal, Pawel Aftanski, Franz Haertel, Sissy Grund, Stephan von Haehling, Ulrike Schumacher, Sven Möbius-Winkler, and Martin Busch
Subjects: Heart Failure, Sodium, Kidney, Diuresis, Diabetes Mellitus, Type 2, Glucosides, Sodium Potassium Chloride Symporter Inhibitors, Creatinine, Physiology (medical), Humans, Prospective Studies, Benzhydryl Compounds, Diuretics, Cardiology and Cardiovascular Medicine, Sodium-Glucose Transporter 2 Inhibitors
Abstract: Background: Effective diuretic regimens using loop diuretics in patients with acute decompensated heart failure are often limited by the development of worsening kidney function. Sodium-glucose cotransporter-2 inhibitors induce glucosuria and sodium excretion with nephroprotective effects in patients with stable heart failure but their role in acute decompensated heart failure is unclear. Methods: In this single-center, prospective, double-blind, placebo-controlled, randomized study, we randomly assigned patients with acute decompensated heart failure to empagliflozin 25 mg daily or placebo in addition to standard decongestive treatments that included loop diuretics. The primary end point was cumulative urine output over 5 days. Secondary end points included diuretic efficiency, dynamics in markers of kidney function and injury, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Results: Sixty patients were randomized within 12 hours of hospitalization for acute decompensated heart failure. Addition of empagliflozin daily to standard medical treatment of acute decompensated heart failure resulted in a 25% increase in cumulative urine output over 5 days (median 10.8 versus 8.7 L mL in placebo, group difference estimation 2.2 L [95% CI, 8.4 to 3.6]; P =0.003). Empagliflozin increased diuretic efficiency compared with placebo (14.1 mL urine per milligram furosemide equivalent [95% CI, 0.6–27.7]; P =0.041) without affecting markers of renal function (estimated glomerular filtration rate, 51±19 versus 54±17 mL/min per 1.73 m²; P =0.599) or injury (total urinary protein, 492±845 versus 503±847 mg/g creatinine; P =0.975; and urinary α1-microglobulin, 55.4±38.6 versus 31.3±33.6 mg/g creatinine; P =0.066) with more pronounced decrease in NT-proBNP in the empagliflozin group compared with placebo (−1861 versus −727.2 pg/mL after 5 days; quotient in slope, 0.89 [95% CI, 0.83–0.95]; P Conclusions: Early addition of empagliflozin to standard diuretic therapy increases urine output without affecting renal function in patients with acute decompensated heart failure. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04049045.
Published: 2022
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20. Trikuspidalklappeninsuffizienz

Author: Helge Möllmann, Ralph Stephan von Bardeleben, Henryk Dreger, Jörg Hausleiter, Tibor Kempf, Edith Lubos, Philipp Lurz, Holger Nef, Georg Nickenig, Philip Raake, Christian Opitz, Volker Rudolph, Hendrik Schmidt, P. Christian Schulze, and Stephan Baldus
Published: 2022
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21. Implantation mechanischer Unterstützungssysteme und Herztransplantation bei Patienten mit terminaler Herzinsuffizienz

Author: P. Christian Schulze, Markus J. Barten, Udo Boeken, Gloria Färber, Christian M. Hagl, Christian Jung, David Leistner, Evgenij Potapov, Johann Bauersachs, Philip Raake, Nils Reiss, Diyar Saeed, David Schibilsky, Stefan Störk, Christian Veltmann, Andreas J. Rieth, and Jan Gummert
Subjects: Pulmonary and Respiratory Medicine, Emergency Medicine, Internal Medicine, Surgery, Emergency Nursing, Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine
Published: 2022
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22. Gemeinsamer Kommentar der Deutschen Gesellschaft für Kardiologie (DGK) und der Deutschen Gesellschaft für Thorax‑, Herz- und Gefäßchirurgie (DGTHG) zu den Leitlinien (2021) der ESC/EACTS zum Management von Herzklappenerkrankungen

Author: Stephan Baldus, Johann Bauersachs, Andreas Beckmann, Sabine Bleiziffer, Andreas Böning, Lenard Conradi, Stephan Ensminger, Volkmar Falk, Christian Frerker, Christoph Liebetrau, Helge Möllmann, Volker Rudolph, Volker Schächinger, P. Christian Schulze, Holger Thiele, Thomas Walther, and Friedhelm Beyersdorf
Subjects: Pulmonary and Respiratory Medicine, Surgery, Cardiology and Cardiovascular Medicine
Published: 2022
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23. Right Heart Catheterization and Pulmonary Hemodynamics

Author: Daniel Kretzschmar and P. Christian Schulze
Published: 2022
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24. Kommentar zu den Leitlinien (2021) der ESC zur Diagnose und Behandlung akuter und chronischer Herzinsuffizienz

Author: Stefan Frantz, Stefan Anker, Johann Bauersachs, Michael Böhm, Jana Boer, Sonia Busch, Norbert Frey, Christian A. Perings, Tanja K. Rudolph, Stephan von Haehling, and P. Christian Schulze
Published: 2022
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25. Aufbau und Organisation von Herzinsuffizienz-Netzwerken (HF-NETs) und Herzinsuffizienz-Einheiten (Heart Failure Units [HFUs]) zur Optimierung der Behandlung der akuten und chronischen Herzinsuffizienz – Update 2021

Author: Matthias Pauschinger, Stefan Störk, Christiane E. Angermann, Johann Bauersachs, Raffi Bekeredjian, Friedhelm Beyersdorf, Michael Böhm, Norbert Frey, Jan Gummert, Ingrid Kindermann, Stefan Perings, P. Christian Schulze, Wolfgang von Scheidt, and Philip Raake
Subjects: Cardiology and Cardiovascular Medicine
Published: 2022
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26. Virtual and Augmented Reality in Cardiovascular Care

Author: Raphael Romano Bruno, Jennifer N. Avari Silva, Georg Wolff, Deepak L. Bhatt, Marcus Franz, Bernhard Wernly, P. Christian Schulze, Christian Jung, Malte Kelm, and Jonathan R. Silva
Subjects: medicine.medical_specialty, Rehabilitation, business.industry, medicine.medical_treatment, Psychological intervention, Cardiovascular care, Virtual reality, Imaging modalities, Intensive care, Health care, Medicine, Radiology, Nuclear Medicine and imaging, Medical physics, Augmented reality, Cardiology and Cardiovascular Medicine, business
Abstract: Applications of virtual reality (VR) and augmented reality (AR) assist both health care providers and patients in cardiovascular education, complementing traditional learning methods. Interventionalists have successfully used VR to plan difficult procedures and AR to facilitate complex interventions. VR/AR has already been used to treat patients, during interventions in rehabilitation programs and in immobilized intensive care patients. There are numerous additional potential applications in the catheterization laboratory. By using AR, interventionalists could combine visual fluoroscopy information projected and registered on the patient body with data derived from preprocedural imaging and live fusion of different imaging modalities such as fluoroscopy with echocardiography. Persistent technical challenges to overcome include the integration of different imaging modalities into VR/AR and the harmonization of data flow and interfaces. Cybersickness might exclude some patients and users from the potential benefits of VR/AR. Critical ethical considerations arise in the application of VR/AR in vulnerable patients. In addition, digital applications must not distract physicians from the patient. It is our duty as physicians to participate in the development of these innovations to ensure a virtual health reality benefit for our patients in a real-world setting. The purpose of this review is to summarize the current and future role of VR and AR in different fields within cardiology, its challenges, and perspectives.
Published: 2022
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27. Erhalt von Leistungsfähigkeit und Lebensqualität bei chronischer Herzinsuffizienz

Author: Stephan von Haehling, Michael Arzt, Wolfram Doehner, Frank Edelmann, Ruben Evertz, Nicole Ebner, Christoph Herrmann-Lingen, Tania Garfias-Veitl, Michael Koziolek, Michel Noutsias, P. Christian Schulze, Rolf Wachter, Gerd Hasenfuß, and Ulrich Laufs
Subjects: Cardiology and Cardiovascular Medicine
Published: 2022
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28. Interventionelle Therapie und multidisziplinäre Managementstrategien für die akute Lungenembolie

Author: Alexander Ghanem, Martin Andrassy, Daniel Dürschmied, Georg Fürnau, Tobias Geisler, Marcus Hennersdorf, Maike Knorr, Tobias J. Lange, Antje Masri-Zada, Guido Michels, Stephan Rosenkranz, P. Christian Schulze, Tobias Tichelbäcker, Christiane Tiefenbacher, Heinrike Wilkens, and Stavros Konstantinides
Published: 2023
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29. Efficacy and safety of intravenous iron repletion in patients with heart failure : a systematic review and meta-analysis

Author: Davor Vukadinović, Amr Abdin, Insa Emrich, P. Christian Schulze, Stephan von Haehling, and Michael Böhm
Subjects: Iron repletion, Heart failure, General Medicine, Ferric derisomaltose, Cardiology and Cardiovascular Medicine, Ferric carboxymaltose
Abstract: Introduction AFFIRM-AHF and IRONMAN demonstrated lower rates of the combined endpoint recurrent heart failure (HF) hospitalizations and cardiovascular death (CVD) using intravenous (IV) ferric carboxymaltose (FCM) and ferric derisomaltose (FDI), respectively in patients with HF and iron deficiency (ID) utilizing prespecified COVID-19 analyses. Material and methods We meta-analyzed efficacy, between trial heterogeneity and data robustness for the primary endpoint and CVD in AFFIRM-AHF and IRONMAN. As sensitivity analysis, we analyzed data from all eligible exploratory trials investigating FCM/FDI in HF. Results FCM/FDI reduced the primary endpoint (RR = 0.81, 95% CI 0.69–0.95, p = 0.01, I2 = 0%), with the number needed to treat (NNT) being 7. Power was 73% and findings were robust with fragility index (FI) of 94 and fragility quotient (FQ) of 0.041. Effects of FCM/FDI were neutral concerning CVD (OR = 0.88, 95% CI 0.71–1.09, p = 0.24, I2 = 0%). Power was 21% while findings were fragile with reverse FI of 14 and reversed FQ of 0.006. The sensitivity analysis from all eligible trials (n = 3258) confirmed positive effects of FCM/FDI on the primary endpoint (RR = 0.77, 95% CI 0.66–0.90, p = 0.0008, I2 = 0%), with NNT being 6. Power was 91% while findings were robust (FI of 147 and FQ of 0.045). Effect on CVD was neutral (RR = 0.87, 95% CI 0.71–1.07, p = 0.18, I2 = 0%). Power was 10% while findings were fragile (reverse FI of 7 and reverse FQ of 0.002). Rate of infections (OR = 0.85, 95% CI 0.71–1.02, p = 0.09, I2 = 0%), vascular disorder (OR = 0.84, 95% CI 0.57–1.25, p = 0.34, I2 = 0%) and general or injection-site related disorders (OR = 1.39, 95% CI 0.88–1.29, p = 0.16, I2 = 30%) were comparable between groups. There was no relevant heterogeneity (I2 > 50%) between the trials for any of the analyzed outcomes. Conclusions Use of FCM/FDI is safe and reduces the composite of recurrent HF hospitalizations and CVD, while effects on CVD alone are based on available level of data indeterminate. Findings concerning composite outcomes exhibit a high level of robustness without heterogeneity between trials with FCM and FDI. Graphical Abstract
Published: 2023
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30. Effect of Hemolysis Regarding the Characterization and Prognostic Relevance of Neuron Specific Enolase (NSE) after Cardiopulmonary Resuscitation with Extracorporeal Circulation (eCPR)

Author: Franz Haertel, Josephine Babst, Christiane Bruening, Jurgen Bogoviku, Sylvia Otto, Michael Fritzenwanger, Thomas Gecks, Henning Ebelt, Sven Moebius-Winkler, P. Christian Schulze, and Ruediger Pfeifer
Subjects: neuron specific enolase, hemolysis, hypoxic brain injury, ECMO, CPR, Cerebral Performance Category Scale, intensive care, General Medicine
Abstract: Background: Hemolysis, a common adverse event associated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO), may affect neuron-specific enolase (NSE) levels and potentially confound its prognostic value in predicting neurological outcomes in resuscitated patients without return of spontaneous circulation (ROSC) that require extracorporeal cardiopulmonary resuscitation (eCPR). Therefore, a better understanding of the relationship between hemolysis and NSE levels could help to improve the accuracy of NSE as a prognostic marker in this patient population. Methods: We retrospectively analyzed the records of patients who received a VA-ECMO for eCPR between 2004 and 2021 and were treated in the medical intensive care unit (ICU) of the University Hospital Jena. The outcome was measured clinically by using the Cerebral Performance Category Scale (CPC) four weeks after eCPR. The serum concentration of NSE (baseline until 96 h) was analyzed by enzyme-linked immunosorbent assay (ELISA). To evaluate the ability of individual NSE measurements to discriminate, receiver operating characteristic (ROC) curves were calculated. Serum-free hemoglobin (fHb, baseline until 96 h) served as a marker for identifying a confounding effect of parallel hemolysis. Results: 190 patients were included in our study. A total of 86.8% died within 4 weeks after ICU admission or remained unconscious (CPC 3–5), and 13.2% survived with a residual mild to moderate neurological deficit (CPC 1–2). Starting 24h after CPR, NSE was significantly lower and continued to decrease in patients with CPC 1–2 compared to the group with an unfavorable outcome of CPC 3–5. In addition, when evaluating on the basis of receiver operating characteristic curves (ROC), relevant and stable area under the curve (AUC) values for NSE could be calculated (48 h: 0.85 // 72 h: 0.84 // 96 h: 0.80; p < 0.01), and on the basis of a binary logistic regression model, relevant odds ratios for the NSE values were found even after adjusting for fHb regarding the prediction of an unfavorable outcome of CPC 3–5. The respective adjusted AUCs of the combined predictive probabilities were significant (48 h: 0.79 // 72 h: 0.76 // 96 h: 0.72; p ≤ 0.05). Conclusions: Our study confirms NSE as a reliable prognostic marker for poor neurological outcomes in resuscitated patients receiving VA-ECMO therapy. Furthermore, our results demonstrate that potential hemolysis during VA-ECMO does not significantly impact NSE’s prognostic value. These findings are crucial for clinical decision making and prognostic assessment in this patient population.
Published: 2023
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31. Exercise capacity, physical activity, and morbidity

Author: Brunjes, Danielle L., Kennel, Peter J., and Christian Schulze, P.
Published: 2017
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32. Leitlinien des European Resuscitation Council (ERC) zur kardiopulmonalen Reanimation 2021: Update und Kommentar

Author: Guido Michels, Johann Bauersachs, Bernd W. Böttiger, Hans-Jörg Busch, Burkhard Dirks, Norbert Frey, Carsten Lott, Nadine Rott, Wolfgang Schöls, P. Christian Schulze, and Holger Thiele
Subjects: Anesthesiology and Pain Medicine, General Medicine, Cardiology and Cardiovascular Medicine
Published: 2022
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33. Kardiovaskuläre Hochrisikopatienten: Hilfe bei der LDL-C-Zielwerterreichung

Author: Umidakhon Makhmudova, P. Christian Schulze, Anja Vogt, and Oliver Weingärtner
Subjects: General Agricultural and Biological Sciences
Published: 2021
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34. Prognostic relevance of mitral and tricuspid regurgitation after transcatheter aortic valve implantation: Impact of follow-up time point for decision-making

Author: Laura Bäz, Sven Möbius-Winkler, Mahmoud Diab, Thomas Kräplin, Julian G. Westphal, Karim Ibrahim, P. Christian Schulze, and Marcus Franz
Subjects: Cardiology and Cardiovascular Medicine
Abstract: BackgroundIn patients with aortic stenosis treated by transcatheter aortic valve implantation (TAVI), mitral and tricuspid regurgitation (MR and TR) at baseline and after TAVI are likely to be of prognostic relevance, and questions such as whether and when treatment further improves prognosis in these patients arise.AimsAgainst that background, the purpose of this study was to analyze a variety of clinical characteristics including MR and TR with respect to their potential value as predictors of 2-year mortality after TAVI.MethodsA cohort of 445 typical TAVI patients was available for the study and clinical characteristics were evaluated baseline, 6 to 8 weeks as well as 6 months after TAVI.ResultsIn 39% of the patients relevant (moderate or severe) MR and in 32% of the patients relevant (moderate or severe) TR could be detected at baseline. The rates were 27% for MR (p = 0.001, compared to baseline) and 35% for TR (p = n.s., compared to baseline) at the 6- to 8-week follow-up. After 6 months, relevant MR was observable in 28% (p = 0.036, compared to baseline) and relevant TR in 34% (p = n.s., compared to baseline) of the patients. As predictors of 2-year mortality, a multivariate analysis identified the following parameters for the different time points: sex, age, AS entity, atrial fibrillation, renal function, relevant TR, systolic pulmonary artery pressure (PAPsys), and 6-min walk distance at baseline; clinical frailty scale and PAPsys 6–8 weeks after TAVI and BNP and relevant MR 6 months after TAVI. There was a significantly worse 2-year survival in patients with relevant TR at baseline (68.4% vs. 82.6%, p n = 445) and in patients with relevant MR at 6 months (87.9% vs. 95.2%, p = 0.042; landmark analysis: n = 235).ConclusionThis real-life study demonstrated the prognostic relevance of repeated evaluation of MR and TR before and after TAVI. Choosing the right time point for treatment is a remaining clinical challenge, which should be further addressed in randomized trials.
Published: 2023
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35. Response by Schulze et al to Letter Regarding Article, 'Effects of Early Empagliflozin Initiation on Diuresis and Kidney Function in Patients With Acute Decompensated Heart Failure (EMPAG-HF)'

Author: P. Christian Schulze, Jürgen Bogoviku, Julian Westphal, Pawel Aftanski, Franz Haertel, Sissy Grund, Stephan von Haehling, Ulrike Schumacher, Sven Möbius-Winkler, and Martin Busch
Subjects: Physiology (medical), Cardiology and Cardiovascular Medicine
Published: 2023
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36. Intensive lipid-lowering therapy for early achievement of guideline-recommended LDL-cholesterol levels in patients with ST-elevation myocardial infarction ('Jena auf Ziel')

Author: Umidakhon Makhmudova, Beasat Samadifar, Aurel Maloku, Pellumb Haxhikadrija, Jens-Arndt Geiling, Robert Römer, Bernward Lauer, Sven Möbius-Winkler, Sylvia Otto, P. Christian Schulze, and Oliver Weingärtner
Subjects: General Medicine, Cardiology and Cardiovascular Medicine
Abstract: Background and aims Currently, less than 20% of patients at very high-risk achieve ESC/EAS dyslipidemia guideline-recommended LDL-C target levels in Europe. “Jena auf Ziel—JaZ” is a prospective cohort study in which early combination therapy with atorvastatin 80 mg and ezetimibe 10 mg was initiated on admission in patients with ST-elevation myocardial infarction (STEMI) and lipid-lowering therapy was escalated during follow-up with bempedoic acid and PCSK9 inhibitors to achieve recommended LDL-C targets in all patients. Moreover, we evaluated side-effects of lipid-lowering therapy. Methods Patients admitted with STEMI at Jena University Hospital were started on atorvastatin 80 mg and ezetimibe 10 mg on admission. Patients were followed for EAS/ESC LDL-C target achievement during follow-up. Results A total of 85 consecutive patients were enrolled in the study. On discharge, 32.9% achieved LDL-C targets on atorvastatin 80 mg and ezetimibe 10 mg. After 4–6 weeks, 80% of all patients on atorvastatin 80 mg and ezetimibe started at the index event were on ESC/EAS LDL-C targets. In 20%, combined lipid-lowering therapy was escalated with either bempedoic acid or PCSK9 inhibitors. All patients achieved LDL-C levels of or below 55 mg/dL during follow-up on triple lipid-lowering therapy. Combined lipid-lowering therapy was well-tolerated with rare side effects. Conclusions Early combination therapy with a high-intensity statin and ezetimibe and escalation of lipid-lowering therapy with either bempedoic acid or PCSK9 inhibitors gets potentially all patients with STEMI on recommended ESC/EAS LDL-C targets without significant side effects. Graphical abstract
Published: 2023
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37. Lipid-lowering therapy in patients with peripheral artery disease – a call for action

Author: Umidakhon Makhmudova, Daniel Kretzschmar, P. Christian Schulze, and Oliver Weingärtner
Subjects: Cardiology and Cardiovascular Medicine
Published: 2022
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38. Successful Transcatheter Aortic Valve in JenaValve in Homograft Implantation in a 33-Year-Old Heart Failure Patient After Aortic and Mitral Valve Replacement Due to Severe Endocarditis 18 Years Ago

Author: Selma, Mietz, Mahmoud, Diab, Laura, Bäz, P Christian, Schulze, Sven, Möbius-Winkler, and Marcus, Franz
Subjects: Adult, Heart Failure, Heart Valve Prosthesis Implantation, Transcatheter Aortic Valve Replacement, Endocarditis, Aortic Valve, Heart Valve Prosthesis, Aortic Valve Insufficiency, Humans, Mitral Valve, General Medicine, Allografts, Cardiology and Cardiovascular Medicine
Published: 2022
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39. Initial Invasive or Conservative Strategy for Stable Coronary Disease

Author: Maron D. J., Hochman J. S., Reynolds H. R., Bangalore S., O'Brien S. M., Boden W. E., Chaitman B. R., Senior R., Lopez-Sendon J., Alexander K. P., Lopes R. D., Shaw L. J., Berger J. S., Newman J. D., Sidhu M. S., Goodman S. G., Ruzyllo W., Gosselin G., Maggioni A. P., White H. D., Bhargava B., Min J. K., John Mancini G. B., Berman D. S., Picard M. H., Kwong R. Y., Ali Z. A., Mark D. B., Spertus J. A., Krishnan M. N., Elghamaz A., Moorthy N., Hueb W. A., Demkow M., Mavromatis K., Bockeria O., Peteiro J., Miller T. D., Szwed H., Doerr R., Keltai M., Selvanayagam J. B., Gabriel Steg P., Held C., Kohsaka S., Mavromichalis S., Kirby R., Jeffries N. O., Harrell F. E., Rockhold F. W., Broderick S., Bruce Ferguson T., Williams D. O., Harrington R. A., Stone G. W., Rosenberg Y, ISCHEMIA Research Group: Joseph Ricci, A Tello Montoliu, A I Robero Aniorte, Abbey Mulder, Abhay A Laddu, Abhinav Goyal, Abhishek Dubey, Abhishek Goyal, Abigail Knighton, Abraham Oomman, Adam J Jaskowiak, Adam Kolodziej, Adam Witkowski, Adnan Hameed, Adriana Anesini, Afshan Hussain, Agne Juceviciene, Agne Urboniene, Agnes Jakal, Agnieszka Szramowska, Ahmad Khairuddin, Ahmed Abdel-Latif, Ahmed Adel, Ahmed Aljzeeri, Ahmed Kamal, Ahmed Talaat, Aimee Mann, Aira Contreras, Ajit Kumar, V K Kumar, Akemi Furukawa, Akshay Bagai, Akvile Smigelskaite, Alain Furber, Alain Rheault, Alaine Melanie Loehr, Alan Rosen, Albert Varga, Albertina Qelaj, Alberto Barioli, Aldo Russo, Alec Moorman, Alejandro Gisbert, Aleksandra Fratczak, Aleksandras Laucevicius, Alena Kuleshova, Alessandro Sionis, Alexander A Sirker, Alexander M Chernyavskiy, Alexandra Craft, Alexandra Vazquez, Alexandre Ciappina Hueb, Alexandre S Colafranseschi, Alexandre Schaan de Quadros, Alexandre Tognon, Ali Alghamdi, Alice Manica Muller, Aline Nogueira Rabaça, Aline Peixoto Deiro, Alison Hallam, Allegra Stone, Allison Schley, Almudena Castro, Alvaro Rabelo Ales, Amanda Germann, Amanda O'Malley, Amar Uxa, Amarachi Ojajuni, Amarino C Oliveira Jr, Amber B Hull, Ambuj Roy, Amer Zarka, Amir Janmohamed, Ammani Brown, Ammy Malinay, Amparo Martinez Monzonis, Amy J Richards, Amy Iskandrian, Amy Ollinger, Ana D Djordjevic-Dikic, Ana Fernández Martínez, Ana Gomes Almeida, Ana Paula Batista, Ana Rita Francisco, Ana S Mladenovic, Ana Santana, Anam Siddiqui, Anastasia M Kuzmina-Krutetskaya, Andras Vertes, Andre S Sousa, Andre Gabriel, André Schmidt, Andrea M Lundeen, Andrea Bartykowszki, Andrea Lorimer, Andrea Mortara, Andrea Pascual, Andreia Coelho, Andreia Rocha, Andrés García-Rincón, Andrew G Howarth, Andrew J Moriarty, Andrew Docherty, Andrew Starovoytov, Andrew Zurick, Andrzej Łabyk, Andrzej Swiatkowski, Andy Lam, Anelise Kawakami, Angela Hoye, Angela Kim, Angelique Smit, Angelo Nobre, Anil V Shah, Anja Ljubez, Anjali Anand, Ankush Sachdeva, Ann Greenberg, Ann Luyten, Ann Ostrander, Anna Di Donato, Anna Cichocka-Radwan, Anna Fojt, Anna Plachcinska, Anna Proietti, Anna Teresinska, Anne Marie Webb, Anne Cartwright, Anne Heath, Anne Mackin, Anong Amaritakomol, Anong Chaiyasri, Anoop Chauhan, Anoop Mathew, Anthony Gemignani, Anto Luigi Andres, Antonia Vega, Antonietta Hansen, Antonino Ginel Iglesias, Antonio Carlos Carvalho, Antonio Di Chiara, Antonio Serra Peñaranda, Antonio Carvalho, Antonio Colombo, Antonio Fiarresga, Anupama Rao, Aquiles Valdespino-Estrada, Araceli Boan, Areef Ishani, Ariel Diaz, Arijit Ghosh, Arintaya Prommintikul, Arline Roberts, Arnold H Seto, Arnold P Good, Arshed Quyyumi, Arthur J Labovitz, Arthur Kerner, Arturo S Campos-Santaolalla, Arunima Misra, Ashok Mukherjee, Ashok Seth, Ashraf Seedhom, Asim N Cheema, Asker Ahmed, Atul Mathur, Atul Verma, Audrey W Leong, Axel Åkerblom, Axelle Fuentes, Aynun Naher, Badhma Valaiyapathi, Baljeet Kaur, Bandula Guruge, Barbara Brzezińska, Barbara Nardi, Bartosz Czarniak, Bebek Singh, Begoña Igual, Bela Merkely, Belen Cid Alvarez, Benjamin J Spooner, Benjamin J W Chow, Benjamin Cheong, Benoy N Shah, Bernard de Bruyne, Bernardas Valecka, Bernhard Jäger, Beth A Archer, Beth Abramson, Beth Jorgenson, Bethany Harvey, Betsy O'Neal, Bev Atkinson, Bev Bozek, Bevin Lang, Bijulal Sasidharan, Bin Yang, Bin Zhang, Binoy Mannekkattukudy Kurian, Bjoern Goebel, Bob Hu, Bogdan A Popescu, Bogdan Crnokrak, Bolin Zhu, Bonnie J Kirby, Brandi D Zimbelman, Brandy Starks, Branko D Beleslin, Brenda Hart, Brian P Shapiro, Brian McCandless, Brianna Wisniewski, Brigham R Smith, Brooks Mirrer, Bruce McManus, Bruce Rutkin, Bruna Edilena Paulino, Bruna Maria Ascoli, Bryn Smith, Byron J Allen, C Michael Gibson, C Noel Bairey Merz, Calin Pop, Cameron Hague, Camila Thais de Ormundo, Candace Gopaul, Candice P Edillo, Carísi A Polanczyk, Carita Krannila, Carla Vicente, Carl-Éric Gagné, Carlo Briguori, Carlos Peña Gil, Carlos Alvarez, Carly 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Bermudez, Eapen Punnoose, Edgar L Tay, Edgar Karanjah, Edoardo Verna, Eduardo Hernandez-Rangel, Edward D Nicol, Edward O McFalls, Edward T Martin, Edyta Kaczmarska, Ekaterina I Lubinskaya, Elena A Demchenko, Elena Refoyo Salicio, Eli Feen, Elihú Durán-Cortés, Elisabeth M Janzen, Elise L Hannemann, Elise van Dongen, Elissa Restelli Piloto, Eliza Kaplan, Elizabeta Srbinovska Kostovska, Elizabeth Capasso-Gulve, Elizabeth Congdon, Elizabeth Ferguson, Elizaveta V Zbyshevskaya, Ellen Magedanz, Ellie Fridell, Ellis W Lader, Elvin Kedhi, Emanuela Racca, Emilie Tachot, Emily DeRosa, Encarnación Alonso-Álvarez, Eric Nicollet, Eric Peterson, Erick Alexánderson Rosas, Erick Donato Morales, Erin Orvis, Ermina Moga, Estelle Montpetit, Estevao Figueiredo, Eugene Passamani, Eugenia Nikolsky, Eunice Yeoh, Evgeniy I Kretov, Ewa Szczerba, Ewelina Wojtala, Expedito Eustáquio Ribeiro Silva, F Marin Ortuño, Fabio R Farias, Fabio Fimiani, Fabrizio Rolfo, Fa-Chang Yu, Fadi Hage, Fadi Matar, Fahim Haider 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Niedzwiecka, J David Knight, Jacek Kusmierek, Jackie M White, Jackie Chow, Jacob Udell, Jacqueline E Tamis-Holland, Jacqueline Fannon, Jacquelyn A Quin, Jacquelyn Do, Jaekyeong Heo, Jakub Maksym, James E Davies, James H O'Keefe Jr, James J Jang, James Cha, James Harrison, James Hirsch, James Stafford, James Tatoulis, Jamie Rankin, Jan Henzel, Jan Orga, Jana Tancredi, Janaina Oliveira, Jane Burton, Jane Eckstein, Jane Marucci, Janet P Knight, Janet Blount, Janet Halliday, Janetta Kourzenkova, Janitha Raj, Jan-Malte Sinning, Jaqueline Pozzibon, Jaroslaw Drozdz, Jaroslaw Karwowski, Jason D Glover, Jason Loh Kwok, Jason T Call, Jason Linefsky, Jassira Gomes, Jati Anumpa, Javier J Garcia, Javier Courtis, Jay Meisner, K Jayakumar, Jayne Scales, Jean E Denaro, Jean Michel Juliard, Jean Ho, Jeanette K Stansborough, Jean-Michel Juliard, Jeanne Russo, Jeannette J M Schoep, Jeet Thambyrajah, Jeff Leimberger, Jeffery A Breall, Jeffrey A Kohn, Jeffrey C Milliken, Jeffrey Anderson, Jeffrey Blume, 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Reddy, Kirsten J Quiles, Kirsty Abercrombie, Klaus Matschke, Konrad Szymczyk, Koo Hui Chan, Kotiboinna Preethi, Kozhaya Sokhon, Krissada Meemuk, Kristian Thygesen, Kristin M Salmi, Kristin Newby, Kristina Wippler, Kristine Arges, Kristine Teoh, Krystal Etherington, Krystyna Łoboz-Grudzień, Krzysztof W Reczuch, Krzysztof Bury, Krzysztof Drzymalski, Krzysztof Kukuła, Kuo-Tzu Sung, Kurt Huber, Ladda Douangvila, Lance Sullenberger, Larissa Miranda Trama, Laszlone Matics, Laura Drew, Laura Flint, Laura Keinaite, Laura Sarti, Laurel Kolakaluri, Lawrence M Phillips, Lawrence Friedman, Lawrence Phillips, Lazar Velicki, Leah Howell, Leandro C Maranan, Leanne Cox, Ledjalem Daba, Lei Zhang, Lekshmi Dharmarajan, Leo Bockeria, Leonardo Pizzol Caetano, Leonardo Bridi, Leonid L Bershtein, Leszek Sokalski, Li Hai Yan, Li Li, Lia Nijmeijer, Lidia Sousa, Lihong Xu, Lihua Zhang, Lili Zhang, Lilia Schiavi, Lilian Mazza Barbosa, Lillian L Khor, Lina Felix-Stern, Linda L Hall, Linda M Hollenweger, Linda Arcand, Linda Davidson-Ray, Linda Schwarz, Lindsey N Sikora, Lingping Chi, Lino Patricio, Liping Zhang, Lisa Chaytor, Lisa Hatch, Lisa McCloy, Lisa Wong, Liselotte Persson, Lixin Jiang, Liz Low, Ljiljana Pupic, Loïc Bière, Lorenzo Monti, Lori Christensen, Lori Pritchard, Loriane Black, Lori-Ann Desimone, Lori-Ann Larmand, Lorraine McGregor, Louise Morby, Louise Thomson, Luc Harvey, Luciana de Pádua Baptista, Lucilla Garcia, Ludivine Eliahou, Ludmila Helmer, Luis F Smidt, Luis Bernanrdes, Luis Guzman, Luiz A Carvalho, Luyang Xiong, Lynette L Teo, Lynn M Neeson, Lynne Winstanley, M Barbara Srichai-Parsia, M Quintana Giner, M Sowjanya Reddy, M Valdés Chávarri, M Grazia Rossi, Maarten Simoons, Maayan Konigstein, Maciej Lesiak, Maciej Olsowka, Mafalda Selas, Magalie Corfias, Magdalena Madero Rovalo, Magdalena Łanocha, Magdalena Miller, Magdalena Misztal-Teodorczyk, Magdalena Rantinella, Magdy Abdelhamid, Magnolia Jimenez, Mahboob Alam, Mahevamma Mylarappa, Mahfouz El Shahawy, Mahmoud Mohamed, Mahmud Al-Bustami, Majo X Joseph, Malgorzata Frach, Małgorzta Celińska-Spodar, Malte Helm, Manas Chacko, Mandy Murphy, Manitha Vinod, Manjula Rani, Manu Dhawan, Manuela Mombelli, Marcel Weber, Marcello Galvani, Marcelo Jamus Rodrigues, Marcia F Dubin, Marcia F Werner Bayer, Marcin Szkopiak, Marco Antonio Monsalve, Marco Bizzaro Santos, Marco Magnoni, Marco Marini, Marco Sicuro, Marco Zenati, Marcos Valério Coimbra Resende, Marek Roik, Margalit Bentzvi, Margaret Gilsenan, Margaret Iraola, Margot C Quinn, Maria A Alfonso, Maria Antonieta Pereira Moraes, María Dolores Martínez-Ruíz, María Fernanda Canales, Maria Inês Caetano, Maria P Corral, Maria Pérez García, Maria Victoria Actis, Maria Aguirre, Maria Andreasson, Maria Aprile, Maria Colton, Maria Eugenia Martin, Maria Lasala, Maria Lorenzo, Maria Posada, Maria Shier, Maria Thottam, Mariana V Furtado, Mariana Yumi Okada, Marianna D A Dracoulakis, Marianne De Andrade, Mariano Rubio, Marie Essermark, Marielle Scherrer-Crosbie, Marija T Petrovic, Marija Zdravkovic, Marilyn Black, Marina Garcia, Mario J Garcia, Mariola Szulik, Marisa Orgera, Mark A de Belder, Mark Harbinson, Mark Hyun, Mark Peterson, Mark Xavier, Marlowe Mosley, Marta Capinha, Marta Marcinkiewicz-Siemion, Marta Swiderek, Martha Meyer, Martina Ceseri, Martina Tricoli, Marvin Kronenberg, Mary Williams, Mary Ann Champagne, Mary Colleen Rogge, Mary R Soltau, Mary Streif, Massimo Villella, Massoud Leesar, Matei Claudia, Mateusz Solecki, Matías Nicolás Mungo, Matthew Wall Jr, Matthew Budoff, Matthew Jezior, Matthew Luckie, Matthias Friedrich, Mauren P Haeffner, Maximilian Tscharre, Max-Paul Winter, Mayana Almeida, Mayil S Krishnam, Mayuri Patel, Meenakshi Mishra, Megan Manocchia, Meghana Kakade, Melanie J Munro, Melissa D Chaplin, Melissa LeFevre, Mervyn Andiapen, Michael A Gibson, Michael B Rubens, Michael C Turner, Michael D Shapiro, Michael W Lee, Michael Berlowitz, Michael Davidson, Michael Mack, Michael McDaniel, Michael Mumma, Michal Wlodarczyk, Michel G Khouri, Michel S Slama, Michele Rawlins, Michelle M Bonner, Michelle M Seib, Michelle Chang, Michelle Crowder, Michelle Dixon, Michelle Mayon, Michelle McEvoy, Michelle Yee, Miguel M Fernandes, Miguel Nobre Menezes, Miguel Souto Bayarri, Miguel Barrero, Mikhail T Torosoff, Milan R Dobric, Milan Dobric, Milica Nikola Dekleva, Milind Avdhoot Gadkari, Millie Gomez, Min Tun Kyaw, Miriam Brooks, Miroslav Stevo Martinovic, Mitchel B Lustre, Mohammad Tariq Vakani, Mohammad El-Hajjar, Mohammed Al-Amoodi, Mohammed Hussain, Mohammed Saleem, Moisés Blanco-Calvo, Moisés Jiménez-Santos, Mona Bhatia, Monica Rosca, Monika Laukyte, Montserrat Gracida Blanca, Montserrat Vila Perales, Mouaz H Al-Mallah, Moysés de Oliveira Filho, Mpiko Ntsekhe, Muhamed Saric, Mulei Chen, Myriam Brousseau, Myrthes Emy Takiuti, Nada Cemerlic-Adjic, Nadia Asif, Nadia Gakou, Nafisa Hussain, Nana O Katamadze, Nancy L Clapp, Nancy Aedy, Nandita Nataraj, Nanette K Wenger, Naomi Uchida, Nasrul Ismail, Natalia S Oliveira, Natalia de Carvalho Maffei, Natalie Spitzer, Natasha C Putnam, Naved Aslam, Neamat Mowafy, Neeraj Pandit, Neeraj Parakh, Nevena Garcevic, Ngaire Meadows, Nhi N Tran, Nicholas Danchin, Nicki Lakeman, Nicola Johnston, Nicolas W Shammas, Nicole Saint Vrestil, Nicole Deming, Nier Zhong, Niket Patel, Nikola N Boskovic, Nikolaos Karogiannis, Nikos Werner, Nina Johnston, Ning Zhang, Ning Zhou, Niree Hindoyan, Nirmal Kumar, Nitika Chadha, Nitish Naik, Nodira Aripova, Noloyiso Mtana, Nona A Eskelson, Noor Syamira Mokhtar, Noppon Taksaudom, Nor Asiah Basri, Nora Marchelletta, Norma Hogg, Nungshi Jungla, Nuno Ferreira, Oksana A Lubyanaya, Olga B Nikolaeva, Olga Cañavate, Olga Sobrino, Olga Walesiak, Olga Walter, Olga Zdończyk, Olivia J Lim, Olivia Anaya, Olivia Mancilla, Olivier Dubourg, Olugbenga Bello, Omar Almousalli, Omar Thompson, Oni Olurinde, Or Harel, Osama Raheem, Oscar Méndiz, Óscar Prada-Delgado, Oz Shapira, P Christian Schulze, Pachara Panpunuan, Pal Maurovich-Horvat, Pallav Garg, Paloma Moraga, Pam Singh, Pamela Julian, Pamela Ouyang, Pamela Sigel, Pamela Woodard, Panpan Zhou, Paola Emanuela Poggio, Paola Smanio, Paolo Calabro, Paramjit Jeetley, Pascal Goube, Patricia K Nguyen, Patricia Alarie, Patricia Arakelian, Patricia Arsenault, Patricia Blaise, Patricia Brito, Patricia Cowper, Patricia Endsley, Patricia Mieses, Patrick B Alexander, Patrick Donnelly, Patrick Wilmot, Patrycja Lebioda, Paul C Gordon, Paul Der Mesropian, Paul Galiwango, Paul Hauptman, Paul Kennedy, Paula Beardsley, Paula García-González, Paulo Cury Rezende, Paulo Ricardo Caramori, Pavel S Kozlov, Pedro Canas Silva, Pedro Gabriel Melo Barros E Silva, Pedro Píccaro de Oliveira, Pedro Carvalho, Pedro Modas, Pedro Rio, Peeyush Jain, Peiyu He, Peter A McCullough, Peter H Stone, Peter M Pollak, Peter Douglass, Peter Henriksen, Peter OKane, Peter Ong, Philip Jones, Philip Rogal, Philippe Généreux, Philippe Menasche, Philippe Rheault, Phoebe Goold, Pierre Gervais, Pierre Michaud, Pilar Calvillo, Ping Chai, Piotr Jakubowski, Piotr Pruszczyk, Piotr Slomka, Piyamitr Sritara, Poay-Huan Loh, Poonam Sonawane, Pouneh Samadi, Pragnesh P Parikh, Prakash Deedwania, Pranav M Patel, Praneeth Polamuri, Pratiksha Sharma, Precilia Vasquez, Preeti Kamath, Prince Thomas, Priyadarshani Arambam, Puja K Mehta, Purvez Grant, Pushpa Naik, Qi Zhong, Qian Zhao, Qiang Zhou, Qianqian Yuan, Qin Yu, Qingxian Li, Qiulan Xie, Qiutang Zeng, R J Vindhya, R James Gerlach, Rachel King, Rada Vučić, Radmila Lyubarova, Radoslaw Pracon, Raewyn Fisher, Rafael Beyar, Rafael Diaz, Rafael Selgas, Raffaele Bugiardini, Raffaele Fanelli, Raisa Kavalakkat, V S Rajalekshmi, Rajat S Barua, Rajeev Menon, Rajesh Gopalan Nair, Rajesh Francis, Rajiv Narang, Rakesh Yadav, Ralph Alan Huston, T Ramakrishnan, Ramesh de Silva, Rami El Mahmoud, Ramiro Carvalho, Ramon de Jesús-Pérez, Ramona Stevens, Ran Leng, Ranjan Kachru, Ranjit Kumar Nath, Raquel Sanchez, Raven R Dwyer, Raven Lee, Ray Wyman, Raymond C Wong, Raymond W Little, Raymundo Ocaranza Sanchez, Rebecca J Wimmer, Rebecca Bariciano, Rebecca Otis, Rebekah R Herrmann, Reem Yunis, Reinette Hampson, Renato Abdala Karam, Renee C Hessian, Renee Kaneshiro, Reshma Ravindran, Reto Andreas Gamma, Reyna Bhandari, Reza Arsanjani, Ricardo L Lopes, Ricardo Mendes Oliveira, Ricardo Costa, Richa Bhatt, Richard F Davies, Richard H J Trimlett, Richard Goldweit, Rik Hermanides, Rine Nakanishi, Rinu R Sidh, Risha Patel, Rita Coram, Rizwan A Siddiqui, Rob S Beanlands, Robert J Hamburger, Robert K Riezebos, Robert M Donnino, Robert Bojar, Robert Chilton, Robert Guyton, Robert Henderson, Robert Kornberg, Robert Leber, Robert Mao, Robert Stenberg, Roberta P Santos, Roberto René Favaloro, Roberto Amati, Rodolfo G S D Lima, Rodrigo J Cerci, Rogerio Tumelero, Rohit Tandon, Roma Tewari, Romalisa Miranda-Peats, Ron Wald, Ronald A Mastouri, Ronald G Morford, Ronald G Schwartz, Ronald P Pedalino, Rongrong Hu, Ronnell A Hansen, Ronny A Cohen, Rory Hachamovitch, Rosa Homem, Rosa Sandonato, Rosane Laimer, Rosann Gans, Roxanne Yost, Roy Mathew, Rubén Baleón-Espinosa, Ruben Ramos, Rubine Gevorgyan, Rui Ferreira, Rui Jing, Ruth Pérez-Fernández, S K Dwivedi, S Ramakrishnan, Saadat Khan, Sabahat Bokhari, Sabu Thomas, Sadath Lubna, Sajeeda Parveen Khan, Sajeev Chakanalil Govindan, Saket Girotra, Saleem Kassam, Sallie Canada, Salvador Cruz-Flores, Samaa Mohamed, Samantha Ly, Sameh El Kaffas, Samia Massalha, Sampoornima Setty, Samuel Nwosu, Sandeep Seth, Sandeep Singh, Sander R Niehe, Sandra M Rivest, Sandra S Zier, Sandra Ahoud, Sandy Carr, Sanjay Ganapathi, Sanjay Shetty, Sanjeev Sharma, Santa Jimenez, Santhosh Satheesh, Santiago A Garcia, Sara Fernandez, Sara Karlsson, Sara Salkind, Sara Temiyasathit, Sarah Medina Rodriguez, Sarah Beaudry, Sarah Hadjih, Sarah Williams, Sarah Zahrani, Sarju Ralhan, Sasa Hinic, Sasko Kedev, Satinder Singh, Satoshi Yasuda, Satvic Cholenahally Manjunath, Sau Lee, Scott M Kaczkowski, Scott Kinlay, Sean W Hayes, Sebastian Sobczak, Senait Asier, Sergey A Sayganov, Seth I Sokol, Shaheen Pandie, Shaiful Azmi Yahaya, Shamir Mehta, Shao-Ping Nie, Sharad Chandra, Sharder Islam, Sharon Tai, Sheetal Rupesh Karwa, Sheri Ussery, Sheromani Bajaj, Sherron C Crook, Shigeyuki Nishimura, Shintaro Nakano, Shirin Heydari, Shiv Kumar Choudhary, Shivali Patel, Shobana Ganesan, Shruti Pandey, Shuyang Zhang, Shweta Hande, Siddharth Gadage, Sik-Yin V Tan, Silvia Zottis Poletti, Silvia Riera, Silvia Valbuena, Simon Walsh, Simona Maspoli, Simone Savaris, Si-Ting Feng, So Yang Cho, Solomon Yakubov, Songlin Zhu, Songtao Wang, Sonia Guerrero, Sonika Gupta, Sonja Salinger Martinovic, Sonya Brons, Sorin Brener, Sothinathan Gurunathan, Souheil Saba, Soundarya Nayak, Sowjanya Reddy, Srinivasa Potluri, Sriram Sudarshan, Srun Kuanprasert, Stacie Van Oosterhout, Stamatios Lerakis, Stanley E Cobos, Stefan C Bertog, Stefan M Simović, Stefan Weikl, Stefano Di Marco, Stefano Provasoli, Stephanie A Tirado, Stephanie C Boer, Stephanie M Lane, Stephanie Ferket, Stephanie Kelly, Stephanie Wasmiller, Stephen H McKellar, Stephen P Hoole, Stephen Fremes, Stephen Preston, Steve Leung, Steven A Fein, Steven J Lindsay, Steven P Sedlis, Steven Giovannone, Steven Michael, Steven Weitz, Stijn van Vugt, Subhash Banerjee, Sudhir Naik, Suellen Hosino, Sukie Desire, Sukit Yamwong, Suku T Thambar, Sulagna Mookherjee, Suman Singh, Sundeep Mishra, Sunil Kumar Verma, Supap Kulthawong, Supatchara Khwakhong, Surendra Naik, Suresh Babu, Surin Woragidpoonpol, Suryaprakash Narayanappa, Susan Derbyshire, Susan Gent, Susan Mathus, Susan Milbrandt, Susan Moore, Susan Regan, Susan Stinson, Susan Webber, Susana Silva, Susanna Stevens, Susanne Gruensfelder, Suthara Aramcharoen, Suvarna Kolhe, Suzana Tavares, Suzanne Arnold, Suzanne Welsh, Svetlana Apostolovic, Swapna Kunhunny, Ta-Chuan Hung, Taissa Zappernick, Tali Sharir, Talita Silva, Tamara Colaiácovo Soares, Tapan Umesh Pillay, Tarun K Mittal, Tatiana Trifonova, Tauane Bello Duarte, Tauqir Huk, Téodora Dutoiu, Terrance Chua, Terry Weyand, Thabitha Charles, Theodoros Kofidis, Theresa McCreary, Thierry Lefevre, Thippeekaa Arumairajah, Thitipong Tepsuwan, Thomas J Mulhearn, Thomas M Meyer, Thomas P Rocco, Thomas R Downes, Thomas Crain, Thomas Haldis, Thomas Mathew, Thomas Redick, Thounaojam Indira Devi, Thuraia Nageh, Tia Cauthren, Tiago Silva, Tiffany Little, Tijana Andric, Tina Harding, Titus Lau, Tiziana Formisano, Tiziano Moccetti, Tomasz Ciurus, Tomasz Mazurek, Tomasz Tarchalski, Toshiyuki Nagai, Tri Tran, Tricia Youn, Trish Tucker, Trudie Milner, Tuhina Bose, Tushar Kotecha, Udo Sechtem, Uma S Valeti, Umberto Cucchini, Umesh Badami, Upendra Kaul, V K Bahl, V S Narain, Valentina Casali, Valeria Godoy, Valerie Robesyn, Vamshi P Priya, Vandana Yadav, Vera McKinney, Veronica De Lenges, Veronica Tinnirello, Vicente Miro, Victor Navarro, Victoria Gumerova, Victoria Hernandez, Vidya Seeratan, Vijay Kumar, Vikentiy Y Kozulin, Viktoria Bulkley, Vilmar Veiga Jr, Vincent Setang, C P Vineeth, Virginai Pubull Nuñez, Virginia Fernández-Figares, Vitor Gomes, Viviana Gabriel, Viviane Dos Santos, Viviane Almeida, Vlad A Iliescu, Vladan Mudrenovic, Vladimir Dzavik, Vojislav L Giga, Walter Enrique Mogrovejo, Wan Xian Chan, Wanda C Marfori, Wanda Parker, Warangkana Mekara, Wassim Nona, Wayne Old, Wayne Pennachi, Weerachai Nawarawong, Wei Chen, Wei Su, Weibing Xing, Wei-Ren Lan, Wenda Crawford, Wendy L Stewart, Wendy Drewes, Wenhua Lin, William B Abernethy, William D Salerno, William F Fearon, William Vergoni, William Weintraub, Winnie C Sia, Wlodzimierz J Musial, Xacobe Flores-Ríos, Xavier Garcia-Moll Marimon, Xi Su, Xiang Ma, Xiangqiong Gu, Xiao Wang, Xiaomei Li, Xiaowei Yao, Xin Fu, Xin Su, Xin Zeng, Xinchun Yang, Xiuhong Li, Xuehua Fang, Xutong Wang, Yaming Geng, Yan Yan, Yanek Pépin-Dubois, Yanfu Wang, Yang Wang, Yanmeng Tian, Yaping Huang, Yechen Han, Yesenia Zambrano, Yi-Hsuan Yang, Ying Tung Sia, Yining Yang, Yitong Ma, Yolayfi Peralta, Yongjian Wu, Yu Kunwu, Yu Zhao, Yudong Peng, Yueh-Hung Lin, Yulan Zhao, Yumei Dong, Yunhai Zhao, Yutthaphan Wannasopha, Yvonne Taul, Zakir Sahul, Zalina Kudzoeva, Zbigniew Kalarus, Zeljko Z Markovic, Zhen Huang, Zheng Ji, Zhenyu Liu, Zhou Yue, Zhulin Zhang, Zhuxi Li, Zile Singh Meharwal, Ziliang Bai, Zixiang Yu, Zohra Huda, Zoltan Davidovits
Subjects: Male, Cardiac Catheterization, Computed Tomography Angiography, medicine.medical_treatment, Myocardial Ischemia, Coronary Disease, Coronary Artery Disease, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Coronary Angiography, ISCHEMIA Research Group, law.invention, Angina, Coronary artery disease, 0302 clinical medicine, Randomized controlled trial, law, Cardiovascular Disease, Myocardial Revascularization, 030212 general & internal medicine, Coronary Artery Bypass, 11 Medical and Health Sciences, Cardiac catheterization, General Medicine, Middle Aged, humanities, Cardiovascular Diseases, Cardiology, Female, Human, medicine.medical_specialty, Ischemia, Article, 03 medical and health sciences, Geriatric cardiology, Percutaneous Coronary Intervention, General & Internal Medicine, Internal medicine, medicine, Humans, Angina, Unstable, Aged, business.industry, Coronary Artery Bypa, Percutaneous coronary intervention, Bayes Theorem, medicine.disease, Heart failure, Quality of Life, business
Abstract: BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).
Published: 2020
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40. Relation of left atrial function with exercise capacity and muscle endurance in patients with heart failure

Author: Jurgen Bogoviku, Mohamed M. Bekhite, Ali Hamadanchi, Julian G. Westphal, Sven Möbius-Winkler, Daniel A. Morris, Marat Fudim, Tarek Bekfani, P. Christian Schulze, Steffen Derlien, Shun Ijuin, Jenny Nisser, and Rüdiger C. Braun-Dullaeus
Subjects: medicine.medical_specialty, Left atrial strain, Exercise intolerance, Ventricular Function, Left, Left atrial, Internal medicine, medicine, Diseases of the circulatory (Cardiovascular) system, Humans, In patient, Muscle, Skeletal, Heart Failure, Exercise Tolerance, Ejection fraction, business.industry, Skeletal muscle function, Area under the curve, Skeletal muscle, Stroke Volume, Original Articles, Exercise capacity, Muscle endurance, medicine.disease, Confidence interval, Peripheral, medicine.anatomical_structure, RC666-701, Heart failure, Cardiology, Original Article, Atrial Function, Left, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Heart failure with preserved ejection fraction
Abstract: Aims Left atrial strain (LAS) and skeletal muscle endurance demonstrate a linear relationship to peak VO2. Less is known about the relationship between central (cardiac) and peripheral (muscle endurance) limitations of exercise capacity in patients with heart failure (HF). We investigated this relationship using novel cardiac markers such as LAS and left atrial ejection fraction (LAEF). Methods We analysed echocardiographic measurements, cardiopulmonary exercise testing, and isokinetic muscle function in 55 subjects with HF and controls (17 heart failure with preserved ejection fraction -HFpEF, 18 heart failure with reduced ejection fraction-HFrEF and 20 healthy controls). Results Patients with reduced LAEF showed reduced peak VO2: 14.3±3.5 vs. 18.5±3.5 ml/min/kg, p=0.003 and reduced muscle endurance (RME): 64.3±23.9 vs. 88.5±32.3 Nm/kg, p=0.028. Patients with reduced LAS showed similar results. Neither left ventricular global longitudinal strain (LVGLS) nor left atrial volume index (LAVI) were associated with RME. The area under the curve of LAS and LAEF in patients with HF in association with RME were (0.76 vs. 0.80) with 95% confidence interval (CI) (0.59–0.96, p=0.012 vs. 0.63–0.98, p=0.006, respectively). Peak torque of the left leg was associated with E/LAS (E: early diastolic) in patients with HFpEF (r=−0.6, p=0.020). Endurance of the left leg was associated with LAEF (r=0.79, p=0.001) in patients with HFrEF. Conclusion LAS/LAEF are potential cardiac markers in demonstrating the link between cardiac and peripheral limitations of exercise capacity. Thus, integrating LAS/LAEF in the evaluation of exercise intolerance in patients with HF could be useful. Funding Acknowledgement Type of funding sources: None.
Published: 2021
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41. Host-pathogen interactions of clinical S. aureus isolates to induce infective endocarditis

Author: Uwe Völker, Christian Schwarz, P. Christian Schulze, Vanessa Hoesker, Yasemin Töre, Frieder Schaumburg, Marcus Franz, Verena Hoerr, Katja Grün, Sabine Ameling, Cornelius Faber, and Silke Niemann
Subjects: Microbiology (medical), Staphylococcus aureus, clinical isolates, Virulence Factors, Immunology, Infectious and parasitic diseases, RC109-216, Biology, medicine.disease_cause, Microbiology, medicine, Endocarditis, Animals, Humans, Pathogen, Host (biology), pathomechanisms, Endocarditis, Bacterial, Staphylococcal Infections, medicine.disease, Infectious Diseases, Infective endocarditis, Host-Pathogen Interactions, endocarditis, Parasitology, Research Article, Research Paper, MRI
Abstract: To evaluate potential pathomechanisms in the induction of infective endocarditis (IE), 34 Staphylococcus aureus (S. aureus) isolates, collected from patients with S. aureus endocarditis and from healthy individuals were investigated both in vitro and in vivo. S. aureus isolates were tested in vitro for their cytotoxicity, invasion and the association with platelets. Virulence factor expression profiles and cellular response were additionally investigated and tested for correlation with the ability of S. aureus to induce vegetations on the aortic valves in vivo. In an animal model of IE valvular conspicuity was assessed by in vivo magnetic resonance imaging at 9.4 T, histology and enrichment gene expression analysis. All S. aureus isolates tested in vivo caused a reliable infection and inflammation of the aortic valves, but could not be differentiated and categorized according to the measured in vitro virulence profiles and cytotoxicity. Results from in vitro assays did not correlate with the severity of IE. However, the isolates differed substantially in the activation and inhibition of pathways connected to the extracellular matrix and inflammatory response. Thus, comprehensive approaches of host-pathogen interactions and corresponding immune pathways are needed for the evaluation of the pathogenic capacity of bacteria. An improved understanding of the interaction between virulence factors and immune response in S. aureus infective endocarditis would offer novel possibilities for the development of therapeutic strategies and specific diagnostic imaging markers.
Published: 2021

42. 51-jähriger Patient mit rezidivierenden Pankreatitiden und auffälligem Blutplasma

Author: Robert Römer, P. Christian Schulze, and Oliver Weingärtner
Subjects: General Medicine
Published: 2023
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43. Targeted Interleukin-9 delivery in pulmonary hypertension: Comparison of immunocytokine formats and effector cell study

Author: Judith Heiss, Katja Grün, Laura Tempel, Mattia Matasci, Andrea Schrepper, Michael Schwarzer, Reinhard Bauer, Martin Förster, Alexander Berndt, Christian Jung, P. Christian Schulze, Dario Neri, and Marcus Franz
Subjects: Clinical Biochemistry, General Medicine, Biochemistry
Abstract: Pulmonary hypertension (PH) is accompanied by pulmonary vascular remodelling. By targeted delivery of Interleukin-9 (IL9) via the immunocytokine F8IL9, beneficial effects could be demonstrated in a mouse model of PH. This study aimed to compare two immunocytokine formats (single-chain Fv and full IgG) and to identify potential target cells of IL9.The Monocrotaline mouse model of PH (PH, n = 12) was chosen to evaluate the treatment effects of F8IL9F8 (n = 12) and F8IgGIL9 (n = 6) compared with sham-induced animals (control, n = 10), the dual endothelin receptor antagonist Macitentan (MAC, n = 12) or IL9-based immunocytokines with irrelevant antigen specificity (KSFIL9KSF, n = 12; KSFIgGIL9 n = 6). Besides comparative validation of treatment effects, the study was focused on the detection and quantification of mast cells (MCs) and regulatory T cells (Tregs).There was a significantly elevated systolic right ventricular pressure (104 ± 36 vs. 45 ± 17 mmHg) and an impairment of right ventricular echocardiographic parameters (RVbasal: 2.52 ± 0.25 vs. 1.94 ± 0.13 mm) in untreated PH compared with controls (p 0.05). Only the groups treated with F8IL9, irrespective of the format, showed consistent beneficial effects (p 0.05). Moreover, F8IL9F8 but not F8IgGIL9 treatment significantly reduced lung tissue damage compared with untreated PH mice (p 0.05). There was a significant increase in Tregs in F8IL9-treated compared with control animals, the untreated PH and the MAC group (p 0.05).Beneficial treatment effects of targeted IL9 delivery in a preclinical model of PH could be convincingly validated. IL9-mediated recruitment of Tregs into lung tissue might play a crucial role in the induction of anti-inflammatory and anti-proliferative mechanisms potentially contributing to a novel disease-modifying concept.
Published: 2022

44. Interventional left atrial appendage occlusion: added value of 3D transesophageal echocardiography for device sizing

Author: Goebel, Björn, Wieg, Stephanie, Hamadanchi, Ali, Otto, Sylvia, Jung, Christian, Kretzschmar, Daniel, Figulla, Hans R., Christian Schulze, P., and Poerner, Tudor C.
Published: 2016
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45. Patent foramen ovale—When to close and how?

Author: Sven Möbius-Winkler, Albrecht Günther, P. Christian Schulze, Marcus Franz, Carsten M. Klingner, Aurel Maloku, Ali Hamadanchi, and Gudrun Dannberg
Subjects: medicine.medical_specialty, business.industry, medicine.disease, Surgery, medicine.anatomical_structure, Pfo closure, Migraine, Occlusion, medicine, Patent foramen ovale, Number needed to treat, Platelet aggregation inhibitor, Cardiology and Cardiovascular Medicine, business, Stroke, Foramen ovale (heart)
Abstract: Closure of a patent foramen ovale (PFO) in patients after cryptogenic/cardioembolic stroke is recommended by current guidelines for patients who are 16–60 years of age with a high-risk PFO (class of recommendation A, level of evidence I). The use of double-disk occlusion devices followed by antiplatelet therapy is recommended. The procedure of interventional PFO closure compared with other interventions in cardiology is rather easy to learn. However, it should be performed carefully to avoid postinterventional complications. The number needed to treat (NNT) to avoid one stroke in 5 years in the RESPECT trial was 42, in the CLOSE trial even lower with 20. In the REDUCE trial, the NNT was 28 at 2 years. This can be reduced by longer follow-up, e.g., at 10 years the NNT is 18. While other conditions such as migraine are currently under investigation with respect to the impact of PFO closure, sufficiently powered trials are lacking so that closure in diseases other than stroke should always be individualized.
Published: 2021
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46. Feasibility of the Big 5—Jena eCS Protocol

Author: P. Christian Schulze, Wilhelm Behringer, Otto W. Witte, Marcus Franz, Rotraud Neumann, Carsten M. Klingner, Moisés F Molina-Fuentes, Albrecht Günther, J.E. Rod, Beatrice Steiniger, Ulf Teichgräber, Thomas E. Mayer, and Lukas Lehmkuhl
Subjects: Aortic valve, medicine.medical_specialty, Cerebrovascular, Ischemia, Pilot Projects, Brain Ischemia, medicine.artery, Ultrasound, medicine, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, Tomography, Cardiovascular thrombi, Ischemic Stroke, Retrospective Studies, Neuroradiology, Aorta, business.industry, medicine.disease, Stroke, Clinical trial, Thromboembolic, medicine.anatomical_structure, Embolism, Ventricle, Cardiac ultrasound, Feasibility Studies, Original Article, Neurology (clinical), Neurosurgery, Radiology, Tomography, X-Ray Computed, business
Abstract: Purpose The most common protocols in the initial diagnostic of acute ischemic stroke do not assess cardiogenic or aortic causes of embolism. These are usually evaluated later by transthoracic (TTE) or transesophageal (TEE) echocardiography. This study aimed to evaluate the feasibility of a diagnostic tool for thoracic cardiovascular thrombi according to the first experience with a new extended cardio-stroke protocol (Big 5—Jena eCS protocol) in acute stroke patients. Methods Retrospective analyses of the tomography scans database of the Jena University Hospital were performed. We included a total of 67 patients in the feasibility analyses, based on the evaluation of three outcomes. Results Primary outcome: the Big 5—Jena eCS protocol was able to detect thoracic cardiovascular thrombi in a total of 20 patients in different locations including the arch of the aorta, the aortic valve, the left atrium, the left atrial appendage, the left ventricle, and the pulmonary arteries. Secondary outcome: implementating the protocol did not result in a significant elevation of the radiation exposure compared to traditional protocols. Tertiary outcome: the new protocol identified seven cases that were considered negative by echocardiography. Conclusion The implementation of an extended cardio-stroke protocol is feasible, no significantly time-consuming, acquiring assessable imaging, and maintaining radiation exposure acceptable. The Big 5—Jena eCS protocol was also able to detect some thrombi not reported by TTE or TEE; however, due to our data’s explorative character, a conclusive comparison with cardiac ultrasound is not possible. A prospective pilot study and clinical trials should be conducted to assess the diagnostic accuracy of this protocol compared to echocardiography and determine the potential impact on diagnostic and treatment decisions.
Published: 2021
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47. 'Priorisierung und Triage' im Kontext kardiovaskulärer Erkrankungen

Author: Marija Velichkov, Sylvia Otto, and P. Christian Schulze
Subjects: Gynecology, 03 medical and health sciences, medicine.medical_specialty, 0302 clinical medicine, business.industry, Internal Medicine, medicine, 030212 general & internal medicine, 030204 cardiovascular system & hematology, business
Published: 2021
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48. Access Site Complications of Peripheral Endovascular Procedures: A Large, Prospective Registry on Predictors and Consequences

Author: Hans Krankenberg, P. Christian Schulze, Daniel Kretzschmar, Sven Daniel Stein, Marcus Thieme, Andrei Ciprian Cacuci, Mohamed Gayed, and Maja Ingwersen
Subjects: Male, medicine.medical_specialty, Vascular access, Arteriovenous fistula, 030204 cardiovascular system & hematology, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Pseudoaneurysm, 0302 clinical medicine, Hematoma, Catheterization, Peripheral, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Vascular closure device, Registries, Child, Retrospective Studies, Hemostatic Techniques, business.industry, Endovascular Procedures, PERIPHERAL VASCULAR INTERVENTION, medicine.disease, Surgery, Peripheral, Femoral Artery, Treatment Outcome, Access site, Female, Cardiology and Cardiovascular Medicine, business
Abstract: Purpose The purpose of this study was to investigate predictors and consequences of acute vascular access site complications (ASCs) related to peripheral endovascular diagnostic or interventional procedures. Despite improvement of puncture techniques, access site–related morbidity and mortality is still considerable. Materials and Methods A total of 5263 participants who underwent 5385 endovascular procedures at a single center were consecutively included in this prospective, observational study. Primary outcomes were ASCs defined as composite of puncture site hematoma, pseudoaneurysm, arteriovenous fistula, and overt puncture site bleeding on the first day after procedure. Results ASCs occurred in 16.6% of peripheral endovascular procedures (78.6% hematomas, 18.9% pseudoaneurysms, 1.4% arteriovenous fistulas, 1.1% overt bleedings). Independent predictors were advanced age [odds ratio (OR) per 10 years: 1.12, p=0.004], female sex (OR men, 0.77; p=0.001), lysis (OR 3.56; p5000 IU, 3.56; p=0.02), time to access (OR per 10 seconds, 1.01; pConclusion ASCs after peripheral endovascular procedures are associated with advanced age, female sex, periprocedural antithrombotic medication, brachial artery access, postinterventional bleeding, and nonuse of vascular closure devices.
Published: 2021
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49. Exercise hemodynamics in heart failure patients with preserved and mid-range ejection fraction: key role of the right heart

Author: P. Christian Schulze, Christoph B. Wiedenroth, Veselin Mitrovic, Khodr Tello, Manuel J. Richter, Christian W. Hamm, Werner Seeger, Stefan Guth, Hossein Ardeschir Ghofrani, Andreas Rieth, Henning Gall, and Steffen D. Kriechbaum
Subjects: medicine.medical_specialty, Cardiac output, Ejection fraction, business.industry, Hemodynamics, General Medicine, 030204 cardiovascular system & hematology, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Ventricle, Interquartile range, Heart failure, Internal medicine, medicine, Cardiology, 030212 general & internal medicine, Cardiology and Cardiovascular Medicine, Pulmonary wedge pressure, business, Heart failure with preserved ejection fraction
Abstract: We sought to explore whether classification of patients with heart failure and mid-range (HFmrEF) or preserved ejection fraction (HFpEF) according to their left ventricular ejection fraction (LVEF) identifies differences in their exercise hemodynamic profile, and whether classification according to an index of right ventricular (RV) function improves differentiation. Patients with HFmrEF and HFpEF have hemodynamic compromise on exertion. The classification according to LVEF implies a key role of the left ventricle. However, RV involvement in exercise limitation is increasingly recognized. The tricuspid annular plane systolic excursion/systolic pulmonary arterial pressure (TAPSE/PASP) ratio is an index of RV and pulmonary vascular function. Whether exercise hemodynamics differ more between HFmrEF and HFpEF than between TAPSE/PASP tertiles is unknown. We analyzed 166 patients with HFpEF (LVEF ≥ 50%) or HFmrEF (LVEF 40–49%) who underwent basic diagnostics (laboratory testing, echocardiography at rest, and cardiopulmonary exercise testing [CPET]) and exercise with right heart catheterization. Hemodynamics were compared according to echocardiographic left ventricular or RV function. Exercise hemodynamics (e.g. pulmonary arterial wedge pressure/cardiac output [CO] slope, CO increase during exercise, and maximum total pulmonary resistance) showed no difference between HFpEF and HFmrEF, but significantly differed across TAPSE/PASP tertiles and were associated with CPET results. N-terminal pro-brain natriuretic peptide concentration also differed significantly across TAPSE/PASP tertiles but not between HFpEF and HFmrEF. In patients with HFpEF or HFmrEF, TAPSE/PASP emerged as a more appropriate stratification parameter than LVEF to predict clinically relevant impairment of exercise hemodynamics. Stratification of exercise hemodynamics in patients with HFpEF or HFmrEF according to LVEF or TAPSE/PASP, showing significant distinctions only with the RV-based strategy. All data are shown as median [upper limit of interquartile range] and were calculated using the independent-samples Mann–Whitney U test or Kruskal–Wallis test. PVR pulmonary vascular resistance; max maximum level during exercise.
Published: 2021
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50. Extracorporeal life support in patients with acute myocardial infarction complicated by cardiogenic shock - Design and rationale of the ECLS-SHOCK trial

Author: Holger Thiele, Alper Öner, Peter Boekstegers, Ingo Voigt, Ulrich Laufs, Malte Kelm, Georg Fuernau, Maria Rubini Gimenez, Hans-Josef Feistritzer, Peter Abel, Christian W. Hamm, Mariuca Vasa-Nicotera, Carsten Tschöpe, Markus Ferrari, Tobias Graf, Carsten Skurk, Christian Karagiannidis, Benjamin Schempf, P. Christian Schulze, Tim Seidler, Tienush Rassaf, Michael R. Preusch, Helge Möllmann, Stephan B. Felix, Ralf Lehmann, Alexander Bufe, Harald Lapp, Christian Jung, Christoph Kadel, Ibrahim Akin, Ralf Muellenbach, Ulf Landmesser, Marcus Hennersdorf, Philipp Lauten, Janine Pöss, Ecls-Shock Investigators, Marko Noc, Hans-Bernd Hopf, Stephan Baldus, Peter Nordbeck, Dirk Westermann, Tomaz Goslar, Ilka Oerlecke, Axel Linke, Steffen Desch, Taoufik Ouarrak, Alexander Lauten, Peter Clemmensen, Felix Meincke, Michael Böhm, Holger Nef, Karsten Lenk, A A Mahabadi, Jutta Franz, Britta Goldmann, Steffen Schneider, Tobias Wengenmayer, Lars S Maier, Bernhard Schieffer, Alexander Kersten, Anne Freund, Thomas J. Dengler, Uwe Zeymer, Stefan Baumanns, Suzanne de Waha-Thiele, Stefan John, Daniel Sedding, Wolfgang Rottbauer, Leonhard Bruch, Melchior Seyfarth, and Burkert Pieske
Subjects: endocrine system, medicine.medical_specialty, medicine.medical_treatment, Myocardial Infarction, Shock, Cardiogenic, Medizin, 030204 cardiovascular system & hematology, Revascularization, law.invention, 03 medical and health sciences, Extracorporeal Membrane Oxygenation, 0302 clinical medicine, Fibrinolytic Agents, Randomized controlled trial, law, Internal medicine, Myocardial Revascularization, medicine, Extracorporeal membrane oxygenation, Humans, Prospective Studies, 030212 general & internal medicine, Myocardial infarction, Coronary Artery Bypass, business.industry, Cardiogenic shock, Prognosis, medicine.disease, 3. Good health, Clinical trial, Sample Size, Shock (circulatory), Quality of Life, Cardiology, Myocardial infarction complications, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract: 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.
Published: 2021
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