Jonas Persson

Background We and others have shown that coronary microcirculatory dysfunction (CMVD) with high resting flow is associated with mortality and heart failure. Aim The hypotheses are that coronary microcirculatory dysfunction is i) secondary to angiopoetin-2 downregulation of thrombomodulin ii) involved in early development of heart failure iii) in the acute development of myocardial injury in sepsis Working plan We utilize an invasive method, thermo-dilution, during coronary angiography to diagnose CMVD. CCS We have recruited a CCS-cohort (n=506) with invasive measures of coronary microcirculatory function, a biobank between 2015 and 2022 (HLF grant 20200758). We will do three new analyses in this unique cohort. Study 1. Analysis of thrombomodulin/angiopoetin-2 complexes in plasma to determine if angiopoetin-2 downregulation of thrombomodulin is associated with CMVD in CCS. Study 2. Analysis of pulse wave velocity from aortic pressure waves to determine the relationship between large artery stiffening and the basal and hyperaemic resistance in the LAD of subjects with CCS. Study 3. Analysis the relationship between CMVD and delta_NT-proBNP/year between inclusion and follow-up. Associations between measures of CMVD and higher delta_NT-proBNP/year will indicate that CMVD is predictive of the development of later CHF in CCS patients without known CHF. Sepsis Study 4. We are recruiting sepsis patients (n=54) with non-normal high-sensitive cardiac troponin T (hs-cTnT

>15 ng/L) in an observational study with invasive measures of coronary microcirculatory function, echocardiography and a biobank. We will investigate if CMVD is involved in myocardial injury in sepsis. Study 5. Analysis of years of lives lost due to myocardial injury and degree of myocardial injury in sepsis. Retrospective cohort study of a large cohort of patients with sepsis in Stockholm (n 3000). Significance Association of CMVD with yearly change in NT-proBNP will confirm involvement of CMVD in the development in CHF and measures of CMVD can be used to identify patients susceptible for CHF. Mechanisms behind glycocalyx shredding in CMVD from experimental models needs to be confirmed in humans. The extent of excess death of myocardial injury in sepsis in relation to comorbidities is not known and needs to be determined. To invasively assess both the coronary macro-and microvascular function is essential to identify mechanisms behind myocardial injury.