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

Ghorbannia, Arash; Ellepola, Chalani D.; Woods, Ronald K.; Ibrahim, El-Sayed H.; Maadooliat, Mehdi; Ramirez, Hilda Martinez; LaDisa, John F.

doi:10.1016/j.echo.2022.09.006

Cited by 9 publications

(35 citation statements)

References 39 publications

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“…Rabbits were anesthetized and BP waveforms at the right carotid and femoral arteries were recorded simultaneously via uid-lled catheters 10 . Consistent with prior work, catheter-based measurements revealed mean BP remained near control levels despite coarctation severity 17 , likely due to the presence of collateral vessels [18][19][20] . Hence, a consistent mean BP was assumed temporally.…”

Section: Methodssupporting

confidence: 83%

“…This allowed for the transfer of peak instantaneous Doppler gradient (PIDG) to corresponding catheter-based peak-instantaneous pressure gradient (PIBPG) i.e. PIDG = 1.76 PIBPG -6.9 17 based on data across a range of coarctation severities seen clinically. PIBPG for FSI simulations at younger ages was therefore calculated from weekly ultrasound data.…”

Section: Methodsmentioning

confidence: 99%

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Temporal evolution of mechanical stimuli from vascular remodeling in response to the severity and duration of aortic coarctation

Azarnoosh

Ghorbannia

Ibrahim

et al. 2022

Preprint

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Coarctation of the aorta (CoA) is one of the most common congenital cardiovascular diseases. CoA patients frequently undergo surgical repair, but hypertension (HTN) is still common. The current treatment guideline has revealed irreversible changes in structure and function, yet revised severity guidelines have not been proposed. Our objective was to quantify temporal alterations in mechanical stimuli and changes in arterial geometry in response to the range of CoA severities and durations seen clinically. Rabbits were exposed to CoA resulting in BPGpp severities of ≤ 10, 10–20, and ≥ 20 mmHg for a duration of ~ 1, 3, or 20 weeks using permanent, dissolvable, and rapidly dissolvable sutures. Elastic moduli and thickness were estimated from imaging and longitudinal fluid-structure interaction (FSI) simulations were conducted at different ages using geometries and boundary conditions measured empirically. Mechanical stimuli were characterized including blood flow velocity patterns, wall tension, and radial strain. Empirical results show vascular alternations including thickening and stiffening proximal to the coarctation with increasing severity and/or duration of CoA. FSI simulations indicate wall tension in the proximal region increases markedly with coarctation severity. Importantly, even mild CoA induced stimuli for remodeling that exceeds values seen in adulthood if not treated early and using a BPGpp lower than the current clinical threshold. The findings are aligned with observations from other species and provide some guidance for the values of mechanical stimuli that could be used to predict the likelihood of HTN in human patients with CoA.

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Section: Methodssupporting

confidence: 83%

Section: Methodsmentioning

confidence: 99%

Temporal evolution of mechanical stimuli from vascular remodeling in response to the severity and duration of aortic coarctation

Azarnoosh

Ghorbannia

Ibrahim

et al. 2022

Preprint

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“…Isoflurane, but a recent study from our group using computational methods to implement simulated conscious hemodynamic conditions did not observe significant changes in velocity and BPG 11 . Values reported for thickness, contraction and relaxation from the preclinical CoA model were obtained ex vivo and not within an in vivo system where dynamic adjustments to HTN are being made.…”

Section: Discussionmentioning

confidence: 57%

“…Experimental procedures were approved by applicable Animal Care and Use Committees and conformed to the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Briefly, New Zealand white rabbits (total 75; N=5-12/group) ~10 weeks old and weighing ~1.0 kg were anesthetized 11 and randomly designated to surgically undergo discrete CoA of varying severity and associated mechanical stimuli within the proximal descending thoracic aorta by tying suture around the aorta distal to the left subclavian branch against a wire of known diameter (1.6, 2.0 or 2.7 mm). CoA severity depended on diameter of the wire used, resulting in BPGpp within the clinical range (mild: ≤12, intermediate: [13][14][15][16][17][18][19], and severe: ≥20 mmHg).…”

Section: Preclinical Model Of Coamentioning

confidence: 99%

Coarctation duration and severity predict risk of hypertension precursors in a preclinical model and hypertensive status among patients

Ghorbannia,

Jurkiewicz,

Nasif

et al. 2023

Preprint

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Coarctation of the aorta (CoA) often leads to hypertension (HTN) post-treatment. There is limited evidence for the current ≥20 mmHg peak-to-peak blood pressure gradient (BPGpp) guideline, which can cause aortic thickening, stiffening and dysfunction. This study sought to find the BPGpp severity and duration that avoids persistent dysfunction in a preclinical model, and test if predictors identified translate to HTN status in CoA patients.Rabbits (N=75; 5-11/group; 10 weeks-old) were exposed to mild, intermediate or severe CoA (≤12, 13-19 & ≥20 mmHg BPGpp) for ∼1, 3 or 22 weeks using dissolvable and permanent sutures with thickening, stiffening, contraction and endothelial function evaluated via multivariate regression analysis. The relevance of findings to CoA patients (N=239; age=0.01-46 years; mean 3.44 years) was similarly tested by retrospective review of predictors (pre-operative BPGpp, age at surgery, etc) vs follow-up HTN status.CoA duration and severity were predictive of remodeling and dysfunction in rabbits and HTN likelihood in CoA patients. Interaction between patient age and BPGpp at surgery were significant contributors to HTN, suggesting preclinical findings translate to human. Machine-learning decision tree analysis uncovered duration and severity values for precursors of HTN in the preclinical model, and HTN at follow-up in CoA patients.These findings suggest the current BPGpp threshold is likely too high to limit activation of processes leading to persistent aortic changes associated with HTN. The resulting decision tree provides a foundation for revising CoA treatment guidelines by considering the interaction between CoA severity and duration to limit the chance of HTN.

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“…Figure 2C shows the best decision tree regression fit to contractile response from rabbit aortic tissue S1). BPGpp values have been converted from estimates via simplified Bernoulli equation to catheter representations using: Doppler gradient=1.62×BPGpp+21.33 from Ghorbannia et al 11 ‡Proximal and distal BP were measured under ≈1 MAC isoflurane after 22 wks using fluid-filled catheters advanced from carotid and femoral arteries to the aortic arch and descending thoracic aorta (diaphragm level), respectively.…”

Section: Preclinical Model Of Coamentioning

confidence: 99%

Coarctation Duration and Severity Predict Risk of Hypertension Precursors in a Preclinical Model and Hypertensive Status Among Patients

Ghorbannia,

Jurkiewicz,

Nasif

et al. 2024

Hypertension

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BACKGROUND: Coarctation of the aorta (CoA) often leads to hypertension) posttreatment. Evidence is lacking for the current >20 mm Hg peak-to-peak blood pressure (BP) gradient (BPGpp) guideline, which can cause aortic thickening, stiffening, and dysfunction. This study sought to find the BPGpp severity and duration that avoid persistent dysfunction in a preclinical model and test if predictors translate to hypertension status in patients with CoA. METHODS: Rabbits (n=75; 5–12/group) were exposed to mild, intermediate, or severe CoA (≤12, 13–19, ≥20 mm Hg BPGpp) for ≈1, 3, or 22 weeks using dissolvable and permanent sutures with thickening, stiffening, contraction, and endothelial function evaluated via multivariate regression. Relevance to patients with CoA (n=239; age, 0.01–46 years; median 3.7 months) was tested by retrospective review of predictors (preoperative BPGpp, surgical age, etc.) versus follow-up hypertension status. RESULTS: CoA duration and severity were predictive of aortic remodeling and active dysfunction in rabbits, and hypertension in patients with CoA. Interaction between patient age and BPGpp at surgery contributed significantly to hypertension, similar to rabbits, suggesting preclinical findings translate to patients. Machine learning decision tree analysis uncovered that preoperative BPGpp and surgical age predict risk of hypertension along with residual postoperative BPGpp. CONCLUSIONS: These findings suggest the current BPGpp threshold determined decades ago is likely too high to prevent adverse coarctation-induced aortic remodeling. The results and decision tree analysis provide a foundation for revising CoA treatment guidelines considering the interaction between CoA severity and duration to limit the risk of hypertension.

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

Cited by 9 publications

References 39 publications

Temporal evolution of mechanical stimuli from vascular remodeling in response to the severity and duration of aortic coarctation

Temporal evolution of mechanical stimuli from vascular remodeling in response to the severity and duration of aortic coarctation

Coarctation duration and severity predict risk of hypertension precursors in a preclinical model and hypertensive status among patients

Coarctation Duration and Severity Predict Risk of Hypertension Precursors in a Preclinical Model and Hypertensive Status Among Patients

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