Pulmonary arterial size and response to sildenafil in chronic thromboembolic pulmonary hypertension.
BACKGROUND
Relative area change (RAC) of the proximal pulmonary artery is a measurement of pulmonary artery distensibility and has been shown to correlate with vasoreactivity studies in patients with idiopathic pulmonary arterial hypertension. We have previously noted a relationship between invasive hemodynamic vasoreactivity testing and long-term response to sildenafil in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). We therefore set out to determine whether RAC can provide useful correlatory non-invasive data.


METHODS
Patients recruited to a randomized, controlled trial (RCT) of sildenafil at 40 mg 3 times daily underwent additional magnetic resonance imaging (MRI) at the baseline of the trial. Eighteen patients had an MRI that led to a diagnosis of inoperable distal CTEPH or significant residual CTEPH post-operatively. The primary end-point was improvement in 6-minute walk test (6MWT) with secondary end-points of right heart catheterization-based hemodynamics, N-terminal pro-brain natriuretic peptide (NT pro-BNP) and functional class. RAC assessed by MRI was correlated with trial end-points.


RESULTS
Fourteen subjects with baseline MRI completed the protocol. RAC was the only baseline variable that correlated at 1 year to the primary end-point of improvement in 6MWT (r = 0.7, p = 0.006), and also to a change in NT pro-BNP (r = 0.59, p = 0.03). Using a cut-off of RAC over 20% there was an 87.5% sensitivity (95% confidence interval [CI]: 45% to 100%) and a 66.7% specificity (95% CI: 22% to 96%) for an improvement in 6MWT of >40 meters.


CONCLUSIONS
RAC correlates with functional response to sildenafil, as measured by the 6MWT, and improved heart function, as measured by NT pro-BNP. RAC shows potential in understanding and possibly predicting treatment response.
Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
Mark R
MR
Toshner
Deepa
D
Gopalan
Jay
J
Suntharalingam
Carmen
C
Treacy
Elaine
E
Soon
Karen K
KK
Sheares
Nicholas W
NW
Morrell
Nicholas
N
Screaton
Joanna
J
Pepke-Zaba
D000328:Adult; D000368:Aged; D006328:Cardiac Catheterization; D002908:Chronic Disease; D005260:Female; D006321:Heart / Q000503:physiopathology; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D010879:Piperazines / Q000627:therapeutic use*; D011651:Pulmonary Artery; D011687:Purines / Q000627:therapeutic use; D020127:Recovery of Function; D012680:Sensitivity and Specificity; D000068677:Sildenafil Citrate; D016037:Single-Blind Method; D013450:Sulfones / Q000627:therapeutic use*; D013923:Thromboembolism / Q000150:complications*; D013997:Time Factors; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use*; D016138:Walking
D010446:Peptide Fragments; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D000068677:Sildenafil Citrate