TY - JOUR

T1 - Implications of cardiac variability with cardiovascular magnetic resonance imaging for calculating trial sample size in pulmonary arterial hypertension

AU - Goransson, Christoffer

AU - Vejlstrup, Niels

AU - Scheike, Thomas

AU - Carlsen, Jørn

PY - 2018

Y1 - 2018

N2 - BackgroundNormally, morbidity precedes mortality in pulmonary arterial hypertension (PAH) and is assessed with recognized surrogate measures of survival. Cardiovascular magnetic resonance (CMR) can assess right ventricular (RV) structure and function which is directly related to survival in PAH. This study describes CMR-assessed weekly cardiac variability in PAH, allowing calculation of sample sizes for trials comparing PAH targeted treatment effects and optimal methods for individual monitoring.MethodsTen clinically stable patients with PAH and ten healthy controls had three CMR examinations at weekly intervals. Stroke volume (SV) and cardiac output (CO) measured at six locations with two CMR-methods were, together with the right and left ventricular volumes and systolic function, assessed for variability, which allowed the calculation of sample sizes for clinically relevant changes.ResultsVariability (SD/mean) for SV and CO was lower in PAH patients than in control subjects (SV = 5.7% vs. 8.9% [p = 0.002]; CO = 6.1% vs. 10.2% [p = 0.003]), allowing a total sample size of 6 patients for a clinically relevant 10 mL change in SV or 4 patients for a 10% increase in CO. For the lowest variability, SV is best measured with cine imaging in the left ventricle, and CO is best measured with flow imaging in the aorta. The RV volumes varied more than did the left ventricular volumes. For systolic function, the RV ejection fraction had the lowest variability (9.7%).ConclusionsLow cardiac variability measured with CMR in PAH enables the statistically strong detection of clinically relevant changes with a small trial sample size.

AB - BackgroundNormally, morbidity precedes mortality in pulmonary arterial hypertension (PAH) and is assessed with recognized surrogate measures of survival. Cardiovascular magnetic resonance (CMR) can assess right ventricular (RV) structure and function which is directly related to survival in PAH. This study describes CMR-assessed weekly cardiac variability in PAH, allowing calculation of sample sizes for trials comparing PAH targeted treatment effects and optimal methods for individual monitoring.MethodsTen clinically stable patients with PAH and ten healthy controls had three CMR examinations at weekly intervals. Stroke volume (SV) and cardiac output (CO) measured at six locations with two CMR-methods were, together with the right and left ventricular volumes and systolic function, assessed for variability, which allowed the calculation of sample sizes for clinically relevant changes.ResultsVariability (SD/mean) for SV and CO was lower in PAH patients than in control subjects (SV = 5.7% vs. 8.9% [p = 0.002]; CO = 6.1% vs. 10.2% [p = 0.003]), allowing a total sample size of 6 patients for a clinically relevant 10 mL change in SV or 4 patients for a 10% increase in CO. For the lowest variability, SV is best measured with cine imaging in the left ventricle, and CO is best measured with flow imaging in the aorta. The RV volumes varied more than did the left ventricular volumes. For systolic function, the RV ejection fraction had the lowest variability (9.7%).ConclusionsLow cardiac variability measured with CMR in PAH enables the statistically strong detection of clinically relevant changes with a small trial sample size.

KW - Pulmonary arterial hypertension

KW - Cardiovascular magnetic resonance imaging

KW - Cardiac variability

KW - Trial sample size

U2 - 10.1016/j.ijcard.2017.11.020

DO - 10.1016/j.ijcard.2017.11.020

M3 - Journal article

C2 - 29506724

VL - 257

SP - 332

EP - 338

JO - International Journal of Cardiology

JF - International Journal of Cardiology

SN - 0167-5273

ER -