The Barriers to Rapid Reperfusion in Acute ST-Elevation Myocardial Infarction.

INTRODUCTION: This study aimed to quantify the contribution of various obstacles to timely reperfusion therapy in acute ST-elevation myocardial infarction (STEMI) and to improve performance in a mixed remote rural/urban region. METHODS: From November 1, 2020 to April 23, 2021, patients with acute STEMI were prospectively monitored with the critical time intervals, treatment modalities, and outcomes registered. Selected clinical decision-makers in 11 hospitals were appointed as improvement agents and systematically provided with weekly updated information about absolute and relative performance. Suggestions for improvements were invited and shared. RESULTS: Only 29% of the 146 patients received reperfusion therapy within recommended time limits [prehospital thrombolysis, 2/48; in-hospital thrombolysis, 0/20; primary percutaneous coronary intervention (pPCI), 37/68, with median intervals from the first medical contact of 44, 49, and 133 min, respectively]. Efficiency varied considerably between health trusts: median time from the first medical contact to prehospital thrombolysis ranged from 29 to 54 min (hazard ratio 4.89). The predominant, remediable causes for delays were erroneous tactical choices and protracted electrocardiographic diagnostication, decision-making, and administration of fibrinolytic medication. During the trial, the time to pPCI was non-significantly reduced. CONCLUSION: We found several targets for system improvements in order to mitigate reperfusion delays along the entire chain of care, regardless of reperfusion modality chosen. More patients should receive prehospital thrombolysis. The most important measures will be training to ensure a more efficient on-site workflow, improved protocols and infrastructure facilitating the communication between first responders and in-hospital clinicians, and education emphasizing prehospital transport times. CLINICAL TRIALS IDENTIFIER: NCT04614805.

Late-Gadolinium Enhancement Interface Area and Electrophysiological Simulations Predict Arrhythmic Events in Patients With Nonischemic Dilated Cardiomyopathy.

OBJECTIVES: This study sought to investigate whether shape-based late gadolinium enhancement (LGE) metrics and simulations of re-entrant electrical activity are associated with arrhythmic events in patients with nonischemic dilated cardiomyopathy (NIDCM). BACKGROUND: The presence of LGE predicts life-threatening ventricular arrhythmias in NIDCM; however, risk stratification remains imprecise. LGE shape and simulations of electrical activity may be able to provide additional prognostic information. METHODS: Cardiac magnetic resonance (CMR)-LGE shape metrics were computed for a cohort of 156 patients with NIDCM and visible LGE and tested retrospectively for an association with an arrhythmic composite endpoint of sudden cardiac death and ventricular tachycardia. Computational models were created from images and used in conjunction with simulated stimulation protocols to assess the potential for re-entry induction in each patient's scar morphology. A mechanistic analysis of the simulations was carried out to explain the associations. RESULTS: During a median follow-up of 1,611 (interquartile range: 881 to 2,341) days, 16 patients (10.3%) met the primary endpoint. In an inverse probability weighted Cox regression, the LGE-myocardial interface area (hazard ratio [HR]: 1.75; 95% confidence interval [CI]: 1.24 to 2.47; p = 0.001), number of simulated re-entries (HR: 1.40; 95% CI: 1.23 to 1.59; p < 0.01) and LGE volume (HR: 1.44; 95% CI: 1.07 to 1.94; p = 0.02) were associated with arrhythmic events. Computational modeling revealed repolarization heterogeneity and rate-dependent block of electrical wavefronts at the LGE-myocardial interface as putative arrhythmogenic mechanisms directly related to the LGE interface area. CONCLUSIONS: The area of interface between scar and surviving myocardium, as well as simulated re-entrant activity, are associated with an elevated risk of major arrhythmic events in patients with NIDCM and LGE and represent novel risk predictors.

Cardiac troponin I degradation in serum of patients with hypertrophic obstructive cardiomyopathy undergoing percutaneous septal ablation.

INTRODUCTION: Troponin has become the most important marker for diagnosing acute myocardial infarction, yet knowledge is scarce regarding appearance of specific degradation fragments in the blood. We have recently described the appearance of intact cardiac troponin I (cTnI) and 7 degradation products in patients suffering from ST-elevation myocardial infarction (STEMI) using Western blot analysis. However, the time resolution in STEMI patients is hampered by the rather vague time point 'onset of pain'. We therefore sought to utilize a time-wise more reliable model of human myocardial necrosis: percutaneous transluminal septal myocardial ablation (PTSMA) of hypertrophic obstructive cardiomyopathy (HOCM). Here the iatrogenic induction of myocardial necrosis occurs in vivo, allowing us to investigate degradation of cTnI by the second. METHODS: Blood samples were obtained from 8 patients with HOCM just prior to initiation of PTSMA and up to 50 h following the procedure. Western blot analysis was performed with subsequent analysis of relative intensities of the bands as compared to the degradation of cTnI in STEMI patients from the ASSENT-2 troponin substudy. RESULTS: We demonstrate intact cTnI and 9 degradation products [molecular weight (MW) 12.0-23.5 kDa]. The bands were comparable in MW to degradation fragments in STEMI. Their early rise in intensity, occurring within few minutes after the alcohol injection, emphasizes how susceptible troponin bands are to chemical/ischemic insults. Moreover, two additional bands were visible in the PTSMA population. CONCLUSION: This work describes the degradation products of troponin I in HOCM patients undergoing PTSMA. The detected bands appear fast and are similar to degradations following STEMI. This model contributes to our knowledge of the degradation patterns of troponin in disease states, and may thus play a role in the interpretation of elevated troponin levels.