Clinical, Experimental, and Computational Validation of a New Doppler-Based Index for Coarctation Severity Assessment

Abstract

Long-term morbidity including hypertension often persists in coarctation patients despite current guidelines. Coarctation severity can be invasively assessed via peak-to-peak catheter pressure gradient (PPCG), which is estimated noninvasively via simplified Bernoulli equation and conventionally reported as peak instantaneous Doppler gradient (PIDG). However, underlying simplifications of the equation limit diagnostic accuracy. We studied the diagnostic performance of a new Doppler-based diastolic index called the continuous flow pressure gradient (CFPG) versus conventional indices in assessing coarctation severity. In a rabbit model mimicking human aortic coarctation, temporal blood pressure waveforms revealed the diastolic instantaneous pressure gradients and spectral Doppler features impacted by coarctation severity. We therefore hypothesized that CFPG provides superior correlation with coarctation gradients measured invasively. PIDG and CFPG were quantified using color flow echocardiography in humans and rabbits with discrete coarctations. Results were compared with PPCG in rabbits (n=34) and arm-leg systolic gradients (n=25) in humans via 1-way analysis of variance, Pearson's correlation, linear regression, and Bland-Altman analysis. A threshold of CFPG ≥ 4.6mm Hg was identified via the Youden index as representative of PPCG ≥ 20mm Hg (the current guideline value for coarctation intervention) in rabbits, while a CFPG ≥1.0mm Hg represented an arm-leg systolic gradient ≥20mm Hg in humans. Accuracy measures revealed superior correlation of CFPG (R2>0.80) and mild receiver operating characteristic improvement (area under the receiver operating characteristic curve, 0.94-0.95) compared with PIDG (R2<0.63; area under the receiver operating characteristic curve, 0.89-0.95). Inter-/intraobserver variability tested by intraclass correlation coefficient revealed measurement reliability with differences ≤8.2% and 10.7%, respectively. Computational simulations of anesthetized versus conscious hemodynamics showed parameters were minimally impacted by isoflurane inherent in the dataused to derive CFPG. These results confirm the potential diagnostic accuracy of CFPG in echocardiography-based coarctation severity assessment. We are optimistic that CFPG will be useful for translation of results from preclinical studies that revisit current guidelines to limit morbidity in humans with aortic coarctation.