Andrea Guala

Modelling and Subject-Specific Validation of the Heart-Arterial Tree System

A modeling approach integrated with a novel subject-specific characterization is here proposed for the assessment of hemodynamic values of the arterial tree. A 1D model is adopted to characterize large-to-medium arteries, while the left ventricle, aortic valve and distal micro-circulation sectors are described by lumped submodels. A new velocity profile and a new formulation of the non-linear viscoelastic constitutive relation suitable for the {Q, A} modeling are also proposed. The model is firstly verified semi-quantitatively against literature data. A simple but effective procedure for obtaining subject-specific model characterization from non-invasive measurements is then designed. A detailed subject-specific validation against in vivo measurements from a population of six healthy young men is also performed. Several key quantities of heart dynamics—mean ejected flow, ejection fraction, and left-ventricular end-diastolic, end-systolic and stroke volumes—and the pressure waveforms (at the central, radial, brachial, femoral, and posterior tibial sites) are compared with measured data. Mean errors around 5 and 8%, obtained for the heart and arterial quantities, respectively, testify the effectiveness of the model and its subject-specific characterization.

Impact of atrial fibrillation on the cardiovascular system through a lumped-parameter approach

Atrial fibrillation (AF) is the most common arrhythmia affecting millions of people in the Western countries and, due to the widespread impact on the population and its medical relevance, is largely investigated in both clinical and bioengineering sciences. However, some important feedback mechanisms are still not clearly established. The present study aims at understanding the global response of the cardiovascular system during paroxysmal AF through a lumped-parameter approach, which is here performed paying particular attention to the stochastic modeling of the irregular heartbeats and the reduced contractility of the heart. AF can be here analyzed by means of a wide number of hemodynamic parameters and avoiding the presence of other pathologies, which usually accompany AF. Reduced cardiac output with correlated drop of ejection fraction and decreased amount of energy converted to work by the heart during blood pumping, as well as higher left atrial volumes and pressures are some of the most representative results aligned with the existing clinical literature and here emerging during acute AF. The present modeling, providing new insights on cardiovascular variables which are difficult to measure and rarely reported in literature, turns out to be an efficient and powerful tool for a deeper comprehension and prediction of the arrythmia impact on the whole cardiovascular system.

Fluid dynamics of heart valves during atrial fibrillation: a lumped parameter-based approach

Atrial fibrillation (AF) consequences on the heart valve dynamics are usually studied along with a valvular disfunction or disease, since in medical monitoring, the two pathologies are often concomitant. Aim of the present work is to study, through a stochastic lumped-parameter approach, the basic fluid dynamics variations of heart valves, when only paroxysmal AF is present with respect to the normal sinus rhythm in absence of any valvular pathology. Among the most common parameters interpreting the valvular function, the most useful turns out to be the regurgitant volume. During AF, both atrial valves do not seem to worsen their performance, while the ventricular efficiency is remarkably reduced.

Compensatory Effect between Aortic Stiffening and Remodelling during Ageing

The arterial tree exhibits a complex spatio-temporal wave pattern, whose healthy behaviour depends on a subtle balance between mechanical and geometrical properties. Several clinical studies demonstrated that such a balance progressively breaks down during ageing, when the aorta stiffens and remodels by increasing its diameter. These two degenerative processes however, have different impacts on the arterial wave pattern. They both tend to compensate for each other, thus reducing the detrimental effect they would have had if they had arisen individually. This remarkable compensatory mechanism is investigated by a validated multi-scale model, with the aim to elucidate how aortic stiffening and remodelling quantitatively impact the complex interplay between forward and reflected backward waves in the arterial network. We focus on the aorta and on the pressure at the ventricular-aortic interface, which epidemiological studies demonstrate to play a key role in cardiovascular diseases.

Central Pressure Appraisal: Clinical Validation of a Subject-Specific Mathematical Model

Introduction Current evidence suggests that aortic blood pressure has a superior prognostic value with respect to brachial pressure for cardiovascular events, but direct measurement is not feasible in daily clinical practice. Aim The aim of the present study is the clinical validation of a multiscale mathematical model for non-invasive appraisal of central blood pressure from subject-specific characteristics. Methods A total of 51 young male were selected for the present study. Aortic systolic and diastolic pressure were estimated with a mathematical model and were compared to the most-used non-invasive validated technique (SphygmoCor device, AtCor Medical, Australia). SphygmoCor was calibrated through diastolic and systolic brachial pressure obtained with a sphygmomanometer, while model inputs consist of brachial pressure, height, weight, age, left-ventricular end-systolic and end-diastolic volumes, and data from a pulse wave velocity study. Results Model-estimated systolic and diastolic central blood pressures resulted to be significantly related to SphygmoCor-assessed central systolic (r = 0.65 p <0.0001) and diastolic (r = 0.84 p<0.0001) blood pressures. The model showed a significant overestimation of systolic pressure (+7.8 (-2.2;14) mmHg, p = 0.0003) and a significant underestimation of diastolic values (-3.2(-7.5;1.6), p = 0.004), which imply a significant overestimation of central pulse pressure. Interestingly, model prediction errors mirror the mean errors reported in large meta-analysis characterizing the use of the SphygmoCor when non-invasive calibration is performed. Conclusion In conclusion, multi-scale mathematical model predictions result to be significantly related to SphygmoCor ones. Model-predicted systolic and diastolic aortic pressure resulted in difference of less than 10 mmHg in the 51% and 84% of the subjects, respectively, when compared with SphygmoCor-obtained pressures.

Oral ondansetron versus domperidone for acute gastroenteritis in pediatric emergency departments: Multicenter double blind randomized controlled trial

The use of antiemetics for vomiting in acute gastroenteritis in children is still a matter of debate. We conducted a double-blind randomized trial to evaluate whether a single oral dose of ondansetron vs domperidone or placebo improves outcomes in children with gastroenteritis. After failure of initial oral rehydration administration, children aged 1–6 years admitted for gastroenteritis to the pediatric emergency departments of 15 hospitals in Italy were randomized to receive one oral dose of ondansetron (0.15 mg/kg) or domperidone (0.5 mg/kg) or placebo. The primary outcome was the percentage of children receiving nasogastric or intravenous rehydration. A p value of 0.014 was used to indicate statistical significance (and 98.6% CI were calculated) as a result of having carried out two interim analyses. 1,313 children were eligible for the first attempt with oral rehydration solution, which was successful for 832 (63.4%); 356 underwent randomization (the parents of 125 children did not give consent): 118 to placebo, 119 to domperidone, and 119 to ondansetron. Fourteen (11.8%) needed intravenous rehydration in the ondansetron group vs 30 (25.2%) and 34 (28.8%) in the domperidone and placebo groups, respectively. Ondansetron reduced the risk of intravenous rehydration by over 50%, both vs placebo (RR 0.41, 98.6% CI 0.20–0.83) and domperidone (RR 0.47, 98.6% CI 0.23–0.97). No differences for adverse events were seen among groups. In a context of emergency care, 6 out of 10 children aged 1–6 years with vomiting due to gastroenteritis and without severe dehydration can be managed effectively with administration of oral rehydration solution alone. In children who fail oral rehydration, a single oral dose of ondansetron reduces the need for intravenous rehydration and the percentage of children who continue to vomit, thereby facilitating the success of oral rehydration. Domperidone was not effective for the symptomatic treatment of vomiting during acute gastroenteritis.

Implications of Asymmetry and Valvular Morphotype on Echocardiographic Measurements of the Aortic Root in Bicuspid Aortic Valve

Background: Transthoracic echocardiography (TTE) and magnetic resonance imaging (MRI) have yielded excellent results in aortic root diameter measurement in patients with tricuspid aortic valve. However, accuracy in bicuspid aortic valve (BAV), often associated with aortic root asymmetry, is not fully defined. The aim of this study was to determine the agreement between TTE and MRI in proximal ascending aortic diameters in patients with BAVs. Methods: Seventy‐six consecutive patients with BAVs (mean age, 53 ± 15 years; 65% men) who underwent both TTE and MRI for ascending aortic assessment in a follow‐up protocol were included in the study. Maximum aortic root and ascending aortic diameters were compared. Results: For the whole population, TTE slightly underestimated aortic root diameter (difference, −0.8 ± 2.9 mm; P = .02). However, agreement was significantly better in BAV with fusion of the left and right coronary cusps than with fusion of the right coronary and noncoronary cusps, both with (type 1) and without (type 0) raphe (mean difference, 0.1 ± 2.5 vs −2.8 ± 2.8 mm, P < .001, respectively). In raphe BAV, mean absolute differences of maximum diameters between both techniques were significantly greater in asymmetric versus symmetric aortic roots (3.3 ± 2.2 vs 1.6 ± 1.9 mm, P = .002). BAV type and root asymmetry were independent related to measurement disagreement between both modalities. Conclusions: Although TTE is the technique of choice in the follow‐up of patients with BAVs, aortic root diameter measurements may be inaccurate in the presence of root asymmetry and in BAV with fusion of the right coronary and noncoronary cusps. In these cases, cross‐sectional imaging, with MRI or computed tomography, to confirm aortic diameters may be advisable. HIGHLIGHTSIn patients with BAVs, TTE slightly underestimated aortic root diameter.In BAV, aortic diameter differences by TTE and MRI are ≥3 mm in 39% of cases.Root asymmetry increases aortic root diameter differences between TTE and MRI in BAV.In BAV‐RN, underestimation of aortic root diameter may be significant.TTE‐PSAX helps in root asymmetry diagnosis but has low diameter reproducibility.

Aortic arch tortuosity, a novel biomarker for thoracic aortic disease, is increased in adults with bicuspid aortic valve

INTRODUCTION Arterial tortuosity has emerged as a predictor of adverse outcomes in congenital aortopathies using 3D reconstructed images. We validated a new method to estimate aortic arch tortuosity on 2D CT. We hypothesize that arch tortuosity may identify bicuspid aortic valve (BAV) patients at high risk to develop thoracic aortic aneurysms or aortic dissections (TAD). METHODS BAV subjects with chest CT scans were retrospectively identified in our clinical records and matched to tricuspid aortic valve (TAV) controls by age, gender, and presentation with TAD. Subjects with prior ascending aortic intervention were excluded. Measurements included aortic arch tortuosity, length, angle, width and height. Total aortic tortuosity was estimated in subjects with available abdominal images. RESULTS 120 BAV and 234 TAV subjects were included. Our 2D measurements were highly correlated with 3D midline arch measurements and had high inter- and intra-observer reliability. Compared to TAV, BAV subjects had increased arch tortuosity (median 1.76 [Q1-Q3: 1.62-1.95] vs. 1.63 [1.53-1.78], P < 0.01), length (149 [136-160] vs. 135 [122-152] mm, P < 0.01), height (46 [41-53] vs. 39 [34-47] mm, P < 0.01), and vertex acuity (70 [61-77] vs. 75 [68-81] degree, P < 0.01). In a multivariable analysis, arch tortuosity remained independently associated with BAV after adjusting for aortic diameter and other clinical characteristics. CONCLUSIONS We found that aortic arch tortuosity is significantly increased in BAV and may identify BAV patients who are at increased risk for TAD. Further studies to evaluate the association between tortuosity and clinical outcomes are in progress.

Correction: Central Pressure Appraisal: Clinical Validation of a Subject-Specific Mathematical Model

[This corrects the article DOI: 10.1371/journal.pone.0151523.].