Background Despite favorable outcomes of surgical pulmonary artery (PA) reconstruction, isolated proximal stenting of the central PAs is common clinical practice for patients with peripheral PA stenosis in association with Williams and Alagille syndromes. Given the technical challenges of PA reconstruction and the morbidities associated with transcatheter interventions, the hemodynamic consequences of all treatment strategies must be rigorously assessed. Our study aims to model, assess, and predict hemodynamic outcomes of transcatheter interventions in these patients. Methods and Results Isolated proximal and “extensive” interventions (stenting and/or balloon angioplasty of proximal and lobar vessels) were performed in silico on 6 patient‐specific PA models. Autoregulatory adaptation of the cardiac output and downstream arterial resistance was modeled in response to intervention‐induced hemodynamic perturbations. Postintervention computational fluid dynamics predictions were validated in 2 stented patients and quantitatively assessed in 4 surgical patients. Our computational methods accurately predicted postinterventional PA pressures, the primary indicators of success for treatment of peripheral PA stenosis. Proximal and extensive treatment achieved median reductions of 14% and 40% in main PA systolic pressure, 27% and 56% in pulmonary vascular resistance, and 10% and 45% in right ventricular stroke work, respectively. Conclusions In patients with Williams and Alagille syndromes, extensive transcatheter intervention is required to sufficiently reduce PA pressures and right ventricular stroke work. Transcatheter therapy was shown to be ineffective for long‐segment stenosis and pales hemodynamically in comparison with published outcomes of surgical reconstruction. Regardless of the chosen strategy, a virtual treatment planning platform could identify lesions most critical for optimizing right ventricular afterload.
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Deep phenotyping of cardiac function in heart transplant patients using cardiovascular system models
Right heart catheterization data from clinical records of heart transplant patients are used to identify patient‐specific models of the cardiovascular system. These patient‐specific cardiovascular models represent a snapshot of cardiovascular function at a given post‐transplant recovery time point. This approach is used to describe cardiac function in 10 heart transplant patients, five of which had multiple right heart catheterizations allowing an assessment of cardiac function over time. These patient‐specific models are used to predict cardiovascular function in the form of right and left ventricular pressure‐volume loops and ventricular power, an important metric in the clinical assessment of cardiac function. Outcomes for the longitudinally tracked patients show that our approach was able to identify the one patient from the group of five that exhibited post‐transplant cardiovascular complications.
Heart transplant patients are followed with periodic right heart catheterizations (RHCs) to identify post‐transplant complications and guide treatment. Post‐transplant positive outcomes are associated with a steady reduction of right ventricular and pulmonary arterial pressures, toward normal levels of right‐side pressure (about 20 mmHg) measured by RHC. This study shows that more information about patient progression is obtained by combining standard RHC measures with mechanistic computational cardiovascular system models. The purpose of this study is twofold: to understand how cardiovascular system models can be used to represent a patient's cardiovascular state, and to use these models to track post‐transplant recovery and outcome. To obtain reliable parameter estimates comparable within and across datasets, we use sensitivity analysis, parameter subset selection, and optimization to determine patient‐specific mechanistic parameters that can be reliably extracted from the RHC data. Patient‐specific models are identified for 10 patients from their first post‐transplant RHC, and longitudinal analysis is carried out for five patients. Results of the sensitivity analysis and subset selection show that we can reliably estimate seven non‐measurable quantities; namely, ventricular diastolic relaxation, systemic resistance, pulmonary venous elastance, pulmonary resistance, pulmonary arterial elastance, pulmonary valve resistance and systemic arterial elastance. Changes in parameters and predicted cardiovascular function post‐transplant are used to evaluate the cardiovascular state during recovery of five patients. Of these five patients, only one showed inconsistent trends during recovery in ventricular pressure–volume relationships and power output. At the four‐year post‐transplant time point this patient exhibited biventricular failure along with graft dysfunction while the remaining four exhibited no cardiovascular complications.
- NSF-PAR ID:
- 10455423
- Publisher / Repository:
- Wiley-Blackwell
- Date Published:
- Journal Name:
- The Journal of Physiology
- Volume:
- 598
- Issue:
- 15
- ISSN:
- 0022-3751
- Page Range / eLocation ID:
- p. 3203-3222
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Background Four-dimensional flow cardiovascular magnetic resonance imaging (4D flow CMR) allows comprehensive assessment of pulmonary artery (PA) flow dynamics. Few studies have characterized longitudinal changes in pulmonary flow dynamics and right ventricular (RV) recovery following a pulmonary endarterectomy (PEA) for patients with chronic thromboembolic pulmonary hypertension (CTEPH). This can provide novel insights of RV and PA dynamics during recovery. We investigated the longitudinal trajectory of 4D flow metrics following a PEA including velocity, vorticity, helicity, and PA vessel wall stiffness.
Methods Twenty patients with CTEPH underwent pre-PEA and > 6 months post-PEA CMR imaging including 4D flow CMR; right heart catheter measurements were performed in 18 of these patients. We developed a semi-automated pipeline to extract integrated 4D flow-derived main, left, and right PA (MPA, LPA, RPA) volumes, velocity flow profiles, and secondary flow profiles. We focused on secondary flow metrics of vorticity, volume fraction of positive helicity (clockwise rotation), and the helical flow index (HFI) that measures helicity intensity.
Results Mean PA pressures (mPAP), total pulmonary resistance (TPR), and normalized RV end-systolic volume (RVESV) decreased significantly post-PEA (P < 0.002). 4D flow-derived PA volumes decreased (P < 0.001) and stiffness, velocity, and vorticity increased (P < 0.01) post-PEA. Longitudinal improvements from pre- to post-PEA in mPAP were associated with longitudinal decreases in MPA area (r = 0.68, P = 0.002). Longitudinal improvements in TPR were associated with longitudinal increases in the maximum RPA HFI (r=-0.85, P < 0.001). Longitudinal improvements in RVESV were associated with longitudinal decreases in MPA fraction of positive helicity (r = 0.75, P = 0.003) and minimum MPA HFI (r=-0.72, P = 0.005).
Conclusion We developed a semi-automated pipeline for analyzing 4D flow metrics of vessel stiffness and flow profiles. PEA was associated with changes in 4D flow metrics of PA flow profiles and vessel stiffness. Longitudinal analysis revealed that PA helicity was associated with pulmonary remodeling and RV reverse remodeling following a PEA.
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Abstract Pulmonary vascular distensibility (
α ) is a marker of the ability of the pulmonary vasculature to dilate in response to increases in cardiac output, which protects the right ventricle from excessive increases in afterload. α measured with exercise predicts clinical outcomes in pulmonary hypertension (PH) and heart failure. In this study, we aim to determine if α measured with a passive leg raise (PLR) maneuver is comparable to α with exercise. Invasive cardiopulmonary exercise testing (iCPET) was performed with hemodynamics recorded at three stages: rest, PLR and peak exercise. Four hemodynamic phenotypes were identified (2019 ECS guidelines): pulmonary arterial hypertension (PAH) (n = 10), isolated post‐capillary (Ipc‐PH) (n = 18), combined pre‐/post‐capillary PH (Cpc‐PH) (n = 15), and Control (no significant PH at rest and exercise) (n = 7). Measurements of mean pulmonary artery pressure, pulmonary artery wedge pressure, and cardiac output at each stage were used to calculate α. There was no statistical difference between α‐exercise and α‐PLR (0.87 ± 0.68 and 0.78 ± 0.47% per mmHg, respectively). The peak exercise‐ and PLR‐based calculations of α among the four hemodynamic groups were: Ipc‐PH = Ex: 0.94 ± 0.30, PLR: 1.00 ± 0.27% per mmHg; Cpc‐PH = Ex: 0.51 ± 0.15, PLR: 0.47 ± 0.18% per mmHg; PAH = Ex: 0.39 ± 0.23, PLR: 0.34 ± 0.18% per mmHg; and the Control group: Ex: 2.13 ± 0.91, PLR: 1.45 ± 0.49% per mmHg. Patients withα ≥ 0.7% per mmHg had reduced cardiovascular death and hospital admissions at 12‐month follow‐up. In conclusion, α‐PLR is feasible and may be equally predictive of clinical outcomes as α‐exercise in patients who are unable to exercise or in programs lacking iCPET facilities. -
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Key points Imaging techniques such as contrast echocardiography suggest that anatomical intra‐pulmonary arteriovenous anastomoses (IPAVAs) are present at rest and are recruited to a greater extent in conditions such as exercise. IPAVAs have the potential to act as a shunt, although gas exchange methods have not demonstrated significant shunt in the normal lung.
To evaluate this discrepancy, we compared anatomical shunt with 25‐µm microspheres to contrast echocardiography, and gas exchange shunt measured by the multiple inert gas elimination technique (MIGET).
Intra‐pulmonary shunt measured by 25‐µm microspheres was not significantly different from gas exchange shunt determined by MIGET, suggesting that MIGET does not underestimate the gas exchange consequences of anatomical shunt.
A positive agitated saline contrast echocardiography score was associated with anatomical shunt measured by microspheres. Agitated saline contrast echocardiography had high sensitivity but low specificity to detect a ≥1% anatomical shunt, frequently detecting small shunts inconsequential for gas exchange.
Abstract The echocardiographic visualization of transpulmonary agitated saline microbubbles suggests that anatomical intra‐pulmonary arteriovenous anastomoses are recruited during exercise, in hypoxia, and when cardiac output is increased pharmacologically. However, the multiple inert gas elimination technique (MIGET) shows insignificant right‐to‐left gas exchange shunt in normal humans and canines. To evaluate this discrepancy, we measured anatomical shunt with 25‐µm microspheres and compared the results to contrast echocardiography and MIGET‐determined gas exchange shunt in nine anaesthetized, ventilated canines. Data were acquired under the following conditions: (1) at baseline, (2) 2 µg kg−1 min−1
i.v. dopamine, (3) 10 µg kg−1 min−1i.v. dobutamine, and (4) following creation of an intra‐atrial shunt (in four animals). Right to left anatomical shunt was quantified by the number of 25‐µm microspheres recovered in systemic arterial blood. Ventilation–perfusion mismatch and gas exchange shunt were quantified by MIGET and cardiac output by direct Fick. Left ventricular contrast scores were assessed by agitated saline bubble counts, and separately by appearance of 25‐µm microspheres. Across all conditions, anatomical shunt measured by 25‐µm microspheres was not different from gas exchange shunt measured by MIGET (microspheres: 2.3 ± 7.4%; MIGET: 2.6 ± 6.1%,P = 0.64). Saline contrast bubble score was associated with microsphere shunt (ρ = 0.60,P < 0.001). Agitated saline contrast score had high sensitivity (100%) to detect a ≥1% shunt, but low specificity (22–48%). Gas exchange shunt by MIGET does not underestimate anatomical shunt measured using 25‐µm microspheres. Contrast echocardiography is extremely sensitive, but not specific, often detecting small anatomical shunts which are inconsequential for gas exchange. -
null (Ed.)Cigarette smoking is the single most important risk factor for the development of cardiovascular and pulmonary diseases; however, the role of nicotine in the pathogenesis of these diseases is incompletely understood. The purpose of this study was to examine the effects of chronic nicotine inhalation on the development of cardiovascular and pulmonary disease with a focus on blood pressure and cardiac remodeling. Male C57BL6/J mice were exposed to air (control) or nicotine vapor (daily, 12 hour on/12 hour off) for 8 weeks. Systemic blood pressure was recorded weekly by radio-telemetry, and cardiac remodeling was monitored by echocardiography. At the end of the 8 weeks, mice were subjected to right heart catheterization to measure right ventricular systolic pressure. Nicotine-exposed mice exhibited elevated systemic blood pressure from weeks 1 to 3, which then returned to baseline from weeks 4 to 8, indicating development of tolerance to nicotine. At 8 weeks, significantly increased right ventricular systolic pressure was detected in nicotine-exposed mice compared with the air controls. Echocardiography showed that 8-week nicotine inhalation resulted in right ventricular (RV) hypertrophy with increased RV free wall thickness and a trend of increase in RV internal diameter. In contrast, there were no significant structural or functional changes in the left ventricle following nicotine exposure. Mechanistically, we observed increased expression of angiotensin-converting enzyme and enhanced activation of mitogen-activated protein kinase pathways in the RV but not in the left ventricle. We conclude that chronic nicotine inhalation alters both systemic and pulmonary blood pressure with the latter accompanied by RV remodeling, possibly leading to progressive and persistent pulmonary hypertension.more » « less
