Does cardiac resynchronization therapy restore peripheral circulatory homeostasis?

Aims: To evaluate whether peripheral circulatory ‘remodeling’ as measured by changes in vascular compliance and in markers of nitric oxide signaling contributes to patient response to cardiac resynchronization therapy (CRT) 
Methods and results: Effects of CRT were evaluated in 33 patients pre- and 6 months post- procedure. Peak oxygen consumption (VO2 max), six-minute walk distance (6MWD), NYHA class, and quality of life score (QOL) were evaluated. Augmentation index (AIX) and its interactions with nitric oxide (NO) were evaluated by applanation tonometry. Platelet NO responsiveness and content of thioredoxin-interacting protein (TXNIP) were assessed. Plasma concentrationsof NT-proBNP, asymmetric and symmetric dimethylarginine (ADMA and SDMA), high sensitivity C-reactive protein, catecholamines and matrix metalloproteinases-2 and -9 were assessed. Despite significant improvement in 6MWD (p=0.005), NYHA class (p<0.001), QOL (p=0.001), and all echocardiographic parameters post CRT, there were no significant changesin AIx measurements, TXNIP content and platelet NO response. Significant falls in NTproBNP (p=0.008) and SDMA (p=0.013; independent of renal function) occurred. Falls in SDMA predicted reduction in hs-CRP (p=0.04) and increases in VO2max (p=0.04). There were no correlations between changes in echocardiographic parameters and those in vascular function. 
Conclusions: These data suggest that the beneficial effects of CRT over 6 months are independent of any change in peripheral NO-related signaling. However there is evidence that suppression of inflammation occurs and its magnitude predicts extent of clinical improvement.