Background: The high accuracy of feature-tracking cardiac magnetic resonance (CMR) imaging qualifies this novel modality as potential gold standard for myocardial strain analyses in ST-elevation myocardial infarction patients; however, the incremental prognostic validity of feature-tracking-CMR over left ventricular ejection fraction (LVEF) and myocardial damage remains unclear. This study therefore aimed to determine the value of myocardial strain measured by feature-tracking-CMR for the prediction of clinical outcome following ST-elevation myocardial infarction. Methods: This prospective observational study enrolled 451 revascularized ST-elevation myocardial infarction patients. Comprehensive CMR investigations were performed 3 (interquartile range, 2–4) days after infarction to determine LVEF, global longitudinal strain (GLS), global radial strain, and global circumferential strain as well as myocardial damage. Primary end point was a composite of death, re-infarction, and congestive heart failure (major adverse cardiac events [MACE]). Results: During a follow-up of 24 (interquartile range, 11–48) months, 46 patients (10%) experienced a MACE event. All 3 strain indices were impaired in patients with MACE (all P <0.001). However, GLS emerged as the strongest MACE prognosticator among strain parameters (area under the curve, 0.73 [95% CI, 0.69–0.77]) and was significantly better ( P =0.005) than LVEF (area under the curve, 0.64 [95% CI, 0.59–0.68]). The association between GLS and MACE remained significant ( P <0.001) after adjustment for global radial strain, global circumferential strain, and LVEF as well as for infarct size and microvascular obstruction. The addition of GLS to a risk model comprising LVEF, infarct size, and microvascular obstruction led to a net reclassification improvement (0.35 [95% CI, 0.14–0.55]; P <0.001). Conclusions: GLS by feature-tracking-CMR strongly and independently predicted the occurrence of medium-term MACE in contemporary revascularized ST-elevation myocardial infarction patients. Importantly, the prognostic value of GLS was superior and incremental to LVEF and CMR markers of infarct severity.

Whereas enzymes in the fumarylacetoacetate hydrolase (FAH) superfamily catalyze several distinct chemical reactions, the structural basis for their multi-functionality remains elusive. As a well-studied example, human FAH domain-containing protein 1 (FAHD1) is a mitochondrial protein displaying both acylpyruvate hydrolase (ApH) and oxaloacetate decarboxylase (ODx) activity. As mitochondrial ODx, FAHD1 acts antagonistically to pyruvate carboxylase, a key metabolic enzyme. Despite its importance for mitochondrial function, very little is known about the catalytic mechanisms underlying FAHD1 enzymatic activities, and the architecture of its ligated active site is currently ill defined. We present crystallographic data of human FAHD1 that provide new insights into the structure of the catalytic center at high resolution, featuring a flexible ‘lid’-like helical region which folds into a helical structure upon binding of the ODx inhibitor oxalate. The oxalate-driven structural transition results in the generation of a potential catalytic triad consisting of E33, H30 and an associated water molecule. In silico docking studies indicate that the substrate is further stabilized by a complex hydrogen-bond network, involving amino acids Q109 and K123, identified herein as potential key residues for FAHD1 catalytic activity. Mutation of amino acids H30, E33 and K123 each had discernible influence on the ApH and/or ODx activity of FAHD1, suggesting distinct catalytic mechanisms for both activities. The structural analysis presented here provides a defined structural map of the active site of FAHD1 and contributes to a better understanding of the FAH superfamily of enzymes.

Coronavirus disease 19 (COVID-19) and its associated restrictions could affect ischemic times in patients with ST-segment elevation myocardial infarction (STEMI). The objective of this study was to investigate the influence of the COVID-19 outbreak on ischemic times in consecutive all-comer STEMI patients. We included consecutive STEMI patients (n = 163, median age: 61 years, 27% women) who were referred to seven tertiary care hospitals across Austria for primary percutaneous coronary intervention between 24 February 2020 (calendar week 9) and 5 April 2020 (calendar week 14). The number of patients, total ischemic times and door-to-balloon times in temporal relation to COVID-19-related restrictions and infection rates were analyzed. While rates of STEMI admissions decreased (calendar week 9/10 (n = 69, 42%); calendar week 11/12 (n = 51, 31%); calendar week 13/14 (n = 43, 26%)), total ischemic times increased from 164 (interquartile range (IQR): 107–281) min (calendar week 9/10) to 237 (IQR: 141–560) min (calendar week 11/12) and to 275 (IQR: 170–590) min (calendar week 13/14) (p = 0.006). Door-to-balloon times were constant (p = 0.60). There was a significant difference in post-interventional Thrombolysis in myocardial infarction (TIMI) flow grade 3 in patients treated during calendar week 9/10 (97%), 11/12 (84%) and 13/14 (81%; p = 0.02). Rates of in-hospital death and re-infarction were similar between groups (p = 0.48). Results were comparable when dichotomizing data on 10 March and 16 March 2020, when official restrictions were executed. In this cohort of all-comer STEMI patients, we observed a 1.7-fold increase in ischemic time during the outbreak of COVID-19 in Austria. Patient-related factors likely explain most of this increase. Counteractive steps are needed to prevent further cardiac collateral damage during the ongoing COVID-19 pandemic.