Spum ACS

Inflammation and acute coronary syndromes (ACS)

Novel strategies for prevention and clinical management

Acute coronary syndromes (ACS) are the most frequent causes leading to myocardial infarction, heart failure, and death. The underlying problem is plaque rupture or erosion, with partial or complete occlusion of a major epicardial coronary artery. Activation of inflammatory pathways may trigger such events. Although progress has been made in prevention and treatment of ACS, its complication rate remains high. This is due to the fact that prevention is not well implemented, triggers of the disease are incompletely understood, and diagnosis is only made once myocardial necrosis has occurred. Indeed, inflammatory mechanisms are not yet incorporated into clinical management. Thus, to further improve outcome, multidimensional interventions and patient education should be improved, novel and early diagnostic markers be evaluated, and anti-inflammatory strategies developed.

Research Aims

  • Identification of novel and candidate diagnostic/prognostic biomarkers after ACS. We are screening for novel biomarkers associated with ACS, major adverse cardiovascular events, drug efficacy and safety using systems biology approaches. Moreover, validate candidate biomarkers for risk stratification.
  • CLEVER-ACS trial. We are testing the effects of a short-term anti-inflammatory therapy using everolimus on infarct size, LV remodeling (using MRI) and mTOR-related inflammatory biomarkers and lipids.
  • Intracoronary imaging using intravascular ultrasound (IVUS) and optical coherence tomography (OCT). We are assessing the natural course of bio-absorbable stents for restenosis, neo-atherosclerosis and plaque progression in coronary arteries. We correlate these parameters with novel and candidate plasma biomarkers.
  • Optimization of care and prevention after ACS. As part of the ELIPS program, we are optimizing care in patients after ACS. We test adherence to guidelines and try to detect the areas and causes for non-adherence. As such, we assess achievment of target LDL cholesterol levels in secondary prevention.

Achievements

  • Funding by the SNSF 2009 to 2015. Additional support by local foundations and industry.
  • Excellent patient recruitment: The cohort recruited >3’600 patients into the biomarker cohort, over 1’000 and 100 patients into the interventional COMFORTABLE AMI and imaging IBIS-4 trials, respectively.
  • Completed event adjudication of first cohort (2’200 patients): The 30 days and 1 year follow-up of 2’200 biomarker patients was completed 10/2013 and independent event adjudication finalized 02/2014.
  • Large biobank of > 100’000 patient samples: We are assessing expression profiles of inflammatory cells in blood and coronary thrombi and are performing biomarker analyses in blood, serum and plasma.
  • Excellent local support. This project could be realized thanks to the excellent work of previous and current SPUM fellows, study nurses and the local catheter teams; Zurich SPUM team (Fig. 2).
  • Increasing number of peerreviewed publications

 

Inflammation and acute coronary syndromes (ACS)

Novel strategies for prevention and clinical management

Acute coronary syndromes (ACS) are the most frequent causes leading to myocardial infarction, heart failure, and death. The underlying problem is plaque rupture or erosion, with partial or complete occlusion of a major epicardial coronary artery. Activation of inflammatory pathways may trigger such events. Although progress has been made in prevention and treatment of ACS, its complication rate remains high. This is due to the fact that prevention is not well implemented, triggers of the disease are incompletely understood, and diagnosis is only made once myocardial necrosis has occurred. Indeed, inflammatory mechanisms are not yet incorporated into clinical management. Thus, to further improve outcome, multidimensional interventions and patient education should be improved, novel and early diagnostic markers be evaluated, and anti-inflammatory strategies developed.