title: Implications of ventricular arrhythmia "bursts" with normal epicardial flow, myocardial blush, and ST-segment recovery in anterior ST-elevation myocardial infarction reperfusion: a biosignature of direct myocellular injury "downstream of downstream".
abstract: OBJECTIVE
  Establishing epicardial flow with percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) is necessary but not sufficient to ensure nutritive myocardial reperfusion. We evaluated whether adding myocardial blush grade (MBG) and quantitative reperfusion ventricular arrhythmia "bursts" (VABs) surrogates provide a more informative biosignature of optimal reperfusion in patients with Thrombolysis in Myocardial Infarction (TIMI) 3 flow and ST-segment recovery (STR).
  
  
  RESULTS
  Anterior STEMI patients with final TIMI 3 flow had protocol-blinded analyses of simultaneous MBG, continuous 12-lead electrocardiogram (ECG) STR, Holter VABs, and day 5-14 SPECT imaging infarct size (IS) assessments. Over 20 million cardiac cycles from >4500 h of continuous ECG monitoring in subjects with STR were obtained. IS and clinical outcomes were examined in patients stratified by MBG and VABs. VABs occurred in 51% (79/154) of subjects. Microcirculation (MBG 2/3) was restored in 75% (115/154) of subjects, of whom 53% (61/115) had VABs. No VABs were observed in subjects without microvascular flow (MBG of 0). Of 115 patients with TIMI 3 flow, STR, and MBG 2/3, those with VABs had significantly larger IS (median: 23.0% vs 6.0%, p=0.001). Multivariable analysis identified reperfusion VABs as a factor significantly associated with larger IS (p=0.015).
  
  
  CONCLUSIONS
  Despite restoration of normal epicardial flow, open microcirculation, and STR, concomitant VABs are associated with larger myocardial IS, possibly reflecting myocellular injury in reperfusion settings. Combining angiographic and ECG parameters of epicardial, microvascular, and cellular response to STEMI intervention provides a more predictive "biosignature" of optimal reperfusion than do single surrogate markers.
authors: Duke Clinical Research Institute, Duke University Medical Center, USA Department of Cardiology, Maastricht University Medical Center, The Netherlands.
authors: Mohamed
authors: M
authors: Majidi
authors: Duke Clinical Research Institute, Duke University Medical Center, USA Department of Biostatistics and Bioinformatics, Duke University Medical Center, USA.
authors: Andrzej S
authors: AS
authors: Kosinski
authors: Duke Clinical Research Institute, Duke University Medical Center, USA Department of Medicine, Duke University Medical Center, USA.
authors: Sana M
authors: SM
authors: Al-Khatib
authors: Department of Cardiology, Maastricht University Medical Center, The Netherlands.
authors: Lilian
authors: L
authors: Smolders
authors: Cardiovascular Research Foundation, USA.
authors: Ecaterina
authors: E
authors: Cristea
authors: Department of Medicine, Yale University, USA.
authors: Alexandra J
authors: AJ
authors: Lansky
authors: Cardiovascular Research Foundation, USA Columbia University, USA.
authors: Gregg W
authors: GW
authors: Stone
authors: Cardiovascular Research Foundation, USA Mount Sinai Medical Center, USA.
authors: Roxana
authors: R
authors: Mehran
authors: Mayo Clinic Foundation, USA.
authors: Raymond J
authors: RJ
authors: Gibbons
authors: Department of Cardiology, Maastricht University Medical Center, The Netherlands Cardiovascular Research Institute Maastricht, University of Maastricht, The Netherlands.
authors: Harry J
authors: HJ
authors: Crijns
authors: Cardiovascular Research Institute Maastricht, University of Maastricht, The Netherlands.
authors: Hein J
authors: HJ
authors: Wellens
authors: Department of Cardiology, Maastricht University Medical Center, The Netherlands Cardiovascular Research Institute Maastricht, University of Maastricht, The Netherlands.
authors: Anton P
authors: AP
authors: Gorgels
authors: Duke Clinical Research Institute, Duke University Medical Center, USA Department of Medicine, Duke University Medical Center, USA mitchell.krucoff@duke.edu.
authors: Mitchell W
authors: MW
authors: Krucoff
mesh_terms: D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000503:physiopathology; D003326:Coronary Circulation / Q000502:physiology; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000502:physiology; D008875:Middle Aged; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy*; D015425:Myocardial Reperfusion / Q000009:adverse effects*; D015428:Myocardial Reperfusion Injury / Q000209:etiology* / Q000503:physiopathology; D062645:Percutaneous Coronary Intervention / Q000379:methods; D016896:Treatment Outcome
keywords: ST-segment elevation myocardial infarction; Thrombolysis in Myocardial Infarction 3 flow; myocardial blush grade; percutaneous coronary intervention; reperfusion ventricular arrhythmia bursts; “downstream” response