Name: Christian Eugen Mueller Date of Birth: April 24th, 1968 Marital Status: Married, two childen (15 & 13 years) Nationality: Swiss & German Academic Status: Professor, Chefarzt Position: Director Cardiovascular Research Institute Basel Address: Department of Cardiology, University Hospital Basel Petersgraben 4, 4031 Basel, Tel: 0041 61328 65 49 christian.mueller@usb.ch Website: www.dyspnea.ch

Summary: most important research achievements I would like to divide my research achievements in three parts: first content, second training, motivation, and mentoring of physician scientists, and third strategy. Content: my research aims to contribute to improving the early diagnosis and management of cardiovascular disorders, particularly the most common causes of death and disability in Switzerland: acute myocardial infarction (AMI) and acute heart failure (AHF). I consider seven novel insights of most importance, as all of them had major impact on clinical practice in Switzerland and worldwide, and four of them already resulted in class I recommendations in current clinical practice guidelines of the European Society of Cardiology and widespread clinical implementation. First, systemic plasma concentrations of B-type natriuretic peptide (BNP) and NT-proBNP are quantitative markers of hemodynamic cardiac stress and heart failure and provide incremental value in the early diagnosis and management of patients with suspected AHF (e.g. Mueller C, et al. N Engl J Med 2004, Mueller C, et al. EJHF 2020) Second, high-sensitivity cardiac troponin T and I concentrations as quantitative markers of cardiomyocyte injury provide substantially higher diagnostic accuracy for the early diagnosis of AMI as compared to conventional cardiac troponin assays, or other markers of cardiomyocyte injury (e.g. Reichlin T, et al. N Engl J Med 2009; Kaier T, et al. Circulation 2019). Third, using short-term absolute changes in high-sensitivity cardiac troponin T and I concentrations provides incremental value to their concentrations at presentation to the emergency department and allows an earlier diagnosis of AMI (e.g. Reichlin T, etal. Circulation 2011, Haaf P, et al. Circulation 2012; Neumann J, et al. N Engl J Med 2019). Forth, assay-specific early triage algorithms combining 1h (or 2h) absolute changes in high-sensitivity cardiac troponin T and I concentrations with their concentrations at presentation to the emergency department achieve very high safety and high efficacy both for the early rule-out as well as the early rule-in of AMI. (e.g. Reichlin T, et al. Arch Intern Med 2012, and Boeddinghaus J, et al. Eur Heart J 2018, Boeddinghaus J, et al. Clin Chem 2019, Collet JP, et al. Eur Heart J 2021, Ayala Lopez P, et al. Circulation 2021). Fifth, given the central role that high-sensitivity cardiac troponin T and I concentrations have obtained in the early diagnosis of AMI, non-cardiac sources for cardiac troponin T and I are of major concern. Acute injury and systemic release of skeletal muscle proteins as in acute rhabdomyolysis does not seem to be a non-cardiac cause. In contrast, chronic skeletal muscle disorders, particularly non-inflammatory myopathy and myositis seem to be non-cardiac causes of systemic cardiac troponin T concentrations. Sixth, early intensive and sustained vasodilation using universally available and inexpensive drugs (e.g. nitrates), is relatively well tolerated, but does not improve outcomes in patients with AHF who are stable enough to not require ICU-admission initially (Breidthardt T, et al. JIM 2012, Kozhuharov N, et al. JAMA 2019). Seventh, perioperative myocardial infarction/ injury (PMI) following non-cardiac surgery is a silent and neglected killer (Puelacher C, et al. Circulation 2018). Due to intense anaesthesia and analgesia, it is asymptomatic in 85% of patients and therefore missed in the absence of systematic screening. PMI occurs in about 15% of patients at high CV risk and is associated with a very high risk of death within 30-days (about 10%). Strategies for improved phenotyping and possible therapy are evolving (Puelacher C, et al. JACC 2020; Gualandro DM, et al. Clin Research Cardiol 2021). Training, motivation, and mentoring of physician scientists: Likely my most important and for sure the most rewarding achievement is that with my training, motivation, and mentoring I have been able to contribute to the academic career of several outstanding physician scientists. More than 60 physician scientists have achieved at least one first authorship on a peer-reviewed publication under my supervision. Many of these physician scientists currently pursue an academic career and continue to combine clinical work with research. Six of them have already been appointed professors themselves. Strategy: With the help of the Swiss National Science Foundation, I was able to continuously and sustainably follow a specific strategy when increasing the size and the professionalism of my research team. This strategy has over the years found support and recognition by many stake-holders at the University Hospital Basel and the University of Basel. It also has allowed me to co-found and lead the Cardiovascular Research Institute Basel (CRIB). A) Focus on young physicians and be very inclusive. Attracting young physicians already shortly after graduation into clinical research is mandatory for the identification, training, motivation, and mentoring of the most talented and most capable physician scientists. This allows safe-guarding the academic leaders of the future to our University, but also builds a positive and appreciating attitude towards research in those physicians, who after their research period with me (e.g. during their medical thesis, n=110) will never again have an active role as researchers. This is of key importance as the update and implementation of research findings by practicing physicians is a prerequisite for all research findings to ultimate benefit patients. B) Focus on outcome research with immediate impact on patient care. In order achieve and maintain acceptance and support for clinical research at times of continuously increasing economic pressure in University Hospitals, the immediate benefit of research findings for patient care must be highlighted widely within the hospital, but also to the public. C) Focus on interdisciplinary diagnostic research (precision medicine). This area of clinical medicine has major unmet clinical needs, but also provides unique opportunities for academic-lead research. Thanks to intensive and successful networking over decades, I have been able to create, maintain, and expand an international interdisciplinary consortium, which allows me to conduct cutting-edge research protocols such as e.g. Heart & Muscle.