title: A systematic approach to designing reliable VV optimization methodology: assessment of internal validity of echocardiographic, electrocardiographic and haemodynamic optimization of cardiac resynchronization therapy.
abstract: BACKGROUND
  In atrial fibrillation (AF), VV optimization of biventricular pacemakers can be examined in isolation. We used this approach to evaluate internal validity of three VV optimization methods by three criteria.
  
  
  RESULTS
  Twenty patients (16 men, age 75 ± 7) in AF were optimized, at two paced heart rates, by LVOT VTI (flow), non-invasive arterial pressure, and ECG (minimizing QRS duration). Each optimization method was evaluated for: singularity (unique peak of function), reproducibility of optimum, and biological plausibility of the distribution of optima. The reproducibility (standard deviation of the difference, SDD) of the optimal VV delay was 10 ms for pressure, versus 8 ms (p=ns) for QRS and 34 ms (p<0.01) for flow. Singularity of optimum was 85% for pressure, 63% for ECG and 45% for flow (Chi(2)=10.9, p<0.005). The distribution of pressure optima was biologically plausible, with 80% LV pre-excited (p=0.007). The distributions of ECG (55% LV pre-excitation) and flow (45% LV pre-excitation) optima were no different to random (p=ns). The pressure-derived optimal VV delay is unaffected by the paced rate: SDD between slow and fast heart rate is 9 ms, no different from the reproducibility SDD at both heart rates.
  
  
  CONCLUSIONS
  Using non-invasive arterial pressure, VV delay optimization by parabolic fitting is achievable with good precision, satisfying all 3 criteria of internal validity. VV optimum is unaffected by heart rate. Neither QRS minimization nor LVOT VTI satisfy all validity criteria, and therefore seem weaker candidate modalities for VV optimization. AF, unlinking interventricular from atrioventricular delay, uniquely exposes resynchronization concepts to experimental scrutiny.
authors.affiliation: International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London, UK. andreas.kyriacou@imperial.ac.uk
authors.forename: Andreas
authors.initials: A
authors.lastname: Kyriacou
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Li Kam Wa
authors.forename: Punam A
authors.initials: PA
authors.lastname: Pabari
authors.forename: Beth
authors.initials: B
authors.lastname: Unsworth
authors.forename: Resham
authors.initials: R
authors.lastname: Baruah
authors.forename: Keith
authors.initials: K
authors.lastname: Willson
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Peters
authors.forename: Prapa
authors.initials: P
authors.lastname: Kanagaratnam
authors.forename: Alun D
authors.initials: AD
authors.lastname: Hughes
authors.forename: Jamil
authors.initials: J
authors.lastname: Mayet
authors.forename: Zachary I
authors.initials: ZI
authors.lastname: Whinnett
authors.forename: Darrel P
authors.initials: DP
authors.lastname: Francis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002304:Cardiac Pacing, Artificial / Q000379:methods / Q000592:standards; D058406:Cardiac Resynchronization Therapy / Q000379:methods / Q000592:standards*; D015331:Cohort Studies; D004452:Echocardiography / Q000379:methods / Q000592:standards*; D004562:Electrocardiography / Q000379:methods / Q000592:standards*; D005260:Female; D006439:Hemodynamics / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012107:Research Design / Q000592:standards*