title: Relationship of myocardial substrate characteristics as assessed by myocardial perfusion imaging and cardiac reverse remodeling levels after cardiac resynchronization therapy.
abstract: BACKGROUND
  Cardiac resynchronization therapy (CRT) can provide cardiac reverse remodeling (RR), which may include mechanical reverse remodeling (MRR) and/or electrical reverse remodeling (ERR). However, uncoupling of MRR and ERR is not uncommon, and the underlying mechanisms are not clear. This study aimed to evaluate the relationship of myocardial substrate characteristics as assessed by myocardial perfusion imaging (MPI) and cardiac RR post-CRT.
  
  
  METHODS
  Forty-one patients (26 men, mean age 66 ± 10 years) with heart failure received CRT for at least 12 months were assigned to three groups according to their levels of RR: I, MRR + ERR (ESV reduced ≥15 % and intrinsic QRS duration reduced ≥10 ms); II, MRR only (ESV reduced ≥15 %); and III, non-responder (the others). All the patients also underwent MPI under transient CRT-off to evaluate the intrinsic myocardial substrates, including myocardial scar, LV volumes and function, systolic dyssynchrony, and activation sequences. In addition, ventricular tachycardia (VT) and ventricular fibrillation (VF) detected by the CRT devices during follow-up periods were also recorded.
  
  
  RESULTS
  Quantitative analysis of MPI showed that there were significant differences for scar burden [15.9 ± 9.5, 26.8 ± 16.1, and 45.6 ± 15.1 % for group I (n = 15), II (n = 16), and III (n = 10), respectively, p < 0.001], EDV (136.6 ± 64.9, 221.6 ± 123.9, and 351.8 ± 216.3 ml, p = 0.002), ESV (82.6 ± 59.8, 172.3 ± 117.2, and 293.3 ± 209.6 ml, p = 0.001), LVEF (44.9 ± 15.0, 25.6 ± 10.9, and 21.5 ± 11.7 %, p < 0.001), systolic phase SD (23.4° ± 10.3°, 36.0° ± 16.2°, and 57.0° ± 22.2°, p < 0.001), and bandwidth (72.5° ± 31.1°, 113.4° ± 56.4°, and 199.1° ± 90.1°, p < 0.001). Myocardial scar interfered with the normal propagation of mechanical activation, resulting in heterogeneous activation sequences. Compared with group II (MRR only), group I (ERR + MRR) had significantly less initial activation segments (1.9 ± 1.0 vs. 2.6 ± 0.7, p < 0.05) and shorter maximal contraction delay (46.9° ± 12.9° vs. 58.8° ± 18.5°, p < 0.05). During the periods of follow-up, 21 patients developed VT/VF, including only 1 patient (1 VT) in group I (6.7 %), 8 patients (7 VT and 1 VF) in group II (50 %), and 9 patients (7 VT and 5 VF) in group III (90 %).
  
  
  CONCLUSIONS
  The characteristics of myocardial substrates as assessed by MPI differed significantly between different levels of cardiac RR post-CRT. Myocardial scar played an important role in the development of ERR. Different cardiac RR levels contributed to different incidences of ventricular arrhythmia, and the combination of ERR and MRR provided highest anti-arrhythmic effects.
authors.affiliation: Cardiovascular center, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Kuo-Feng
authors.initials: KF
authors.lastname: Chiang
authors.affiliation: Division of Cardiology, Department of Medicine, Fong Yuan Hospital, Department of Health of Executive Yuan, Taichung, Taiwan.|Institute of Public Health, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chien-Ming
authors.initials: CM
authors.lastname: Cheng
authors.affiliation: Department of Nuclear Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Shih-Chuan
authors.initials: SC
authors.lastname: Tsai
authors.affiliation: Department of Nuclear Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Wan-Yu
authors.initials: WY
authors.lastname: Lin
authors.affiliation: Cardiovascular center, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Chang
authors.affiliation: Cardiovascular center, Taichung Veterans General Hospital, Taichung, Taiwan. golden@vghtc.gov.tw.|Institute of Clinical Medicine, and Cardiovascular Research Institute, Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan. golden@vghtc.gov.tw.
authors.forename: Jin-Long
authors.initials: JL
authors.lastname: Huang
authors.affiliation: Department of Nuclear Medicine, Chang Bing Show Chwan Memorial Hospital, Changhua, Taiwan. 106143@gmail.com.|Department of Biomedical Imaging and Radiological Sciences, China Medical University, Taichung, Taiwan. 106143@gmail.com.
authors.forename: Guang-Uei
authors.initials: GU
authors.lastname: Hung
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, China Medical University, Taichung, Taiwan.
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Kao
authors.affiliation: Institute of Clinical Medicine, and Cardiovascular Research Institute, Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Divisions of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Shih-Ann
authors.initials: SA
authors.lastname: Chen
authors.affiliation: Institute of Public Health, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Pesus
authors.initials: P
authors.lastname: Chou
authors.affiliation: Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Ji
authors.initials: J
authors.lastname: Chen
mesh_terms: D001145:Arrhythmias, Cardiac / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D058406:Cardiac Resynchronization Therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D055414:Myocardial Perfusion Imaging; D009206:Myocardium / Q000473:pathology*
keywords: Cardiac resynchronization; Myocardial perfusion imaging; Myocardial substrate; Reverse remodeling; Ventricular arrhythmia