Search

Introduction: Right Ventricular (RV) dysfunction is the primary aspect of acute right ventricular failure, commonly realized in pulmonary arterial hypertensive (PAH) patients. As a standard clinical assessment for PAH, echocardiographic strain provides a mechanical measure of ventricular deformation during RV contraction. Current strain computation via 2D echo is limited in that imaging and strain are confined to a 2D plane, and thus the technique is unable to fully visualize the asymmetrical deformation of the RV. We believe 3D surface (3DS) strain, obtained from 3D echo (3DE) will overcome this limitation and more thoroughly evaluate myocardial mechanics. In this initial work, we hypothesize that end-systolic 3DS longitudinal and shear freewall strain group means computed from 3DE-cardiac data of the RV will differ between healthy and PAH patient groups. Methods: 3DS strain (longitudinal, circumferential, shear; principal strains, principal angle, and max shear) was computed on the RV freewall at end-systole with finite element analysis post-processing techniques from RV surface meshes obtained from 3DE from 10 normal children and 43 children with idiopathic PAH. Results: 3DS longitudinal and circumferential strain group means were significantly different (p Conclusions: These results suggest that 3DS strain is a promising approach to strain computation with potential to yield more mechanical knowledge of different segments of RV dysfunction. Future work should be directed in the evaluation of focused regional strain specific towards RV dysfunction and evaluate for prognosis.

Introduction: The presence of global vascular dysfunction is a well-recognized feature in youth with type 1 diabetes (T1D). This predisposes young patients to the life-long exposure and increased incidence of cardiovascular events. Therapeutic strategies to mitigate vascular dysfunction are urgently needed. Hypothesis: We hypothesized that bromocriptine quick release (BCQR) therapy would improve vascular health in youth with T1D. Methods: This was a placebo-controlled, random-order, double-blinded, cross-over study investigating BCQR as adjunct therapy on central aortic stiffness as measured by phase-contrast MRI. Participants also underwent flow mediated dilation test and brachial distensibility evaluation using tonometry. Adolescents with T1DM were randomized 1:1 to phase-1 of 4-week BCQR (minimum dose 1.6 mg daily) or placebo therapy after which all vascular measurements were performed. Following a 4-week washout period, phase 2 was performed in identical fashion with the alternate treatment. Results: Forty-two adolescents (mean age 15.9 yrs, HbA1c 8.6%, BMI %ile 71.4, TD duration 5.8 yrs) with T1D were enrolled. BCQR therapy decreased systolic (Δ = -5 mmHg, p < 0.001) and diastolic blood pressure (Δ = -2 mmHg, p = 0.039). BCQR therapy reduced ascending aortic PWV (Δ = -0.4 m/s, p = 0.005), and increased RAC (Δ = -2.6%, p = 0.022), and distensibility (Δ = 0.08 %/mmHg, p = 0.010). In the thoraco-abdominal aorta, BCQR decreased PWV (Δ = -0.2 m/s, p = 0.013) and increased distensibility (Δ = 0.05 %/mmHg, P = 0.032) (FIGURE). In contrast, BCQR decreased RHI (Δ = -0.34, p = 0.006). Conclusions: BCQR therapy improved central aortic stiffness and pressure hemodynamics in adolescents with T1D over 4 weeks. However, BCQR decreased peripheral RHI. BCQR therapy might serve as a potential clinical intervention to attenuate accelerated aortic stiffness in youth with T1D supporting future longer-term studies.

Introduction: Cor Pulmonale or right ventricular (RV) dysfunction due to pulmonary disease is an expected complication of COPD resulting from increased afterload mediated by hypoxic pulmonary vasoconstriction as well as the destruction of the pulmonary vascular bed. Early detection of elevated RV afterload has been previously demonstrated by visualization of abnormal flow patterns in the proximal pulmonary arteries. Prior quantitative analysis of helicity in the pulmonary arteries of pulmonary hypertension patients has demonstrated a strong association between helicity and increased RV afterload. Hypothesis: Patients with COPD will have abnormal pulmonary flow as evaluated by 4D-Flow MRI and associated with RV function and pulmonary arterial stiffness. Methods: Patients with COPD (n=15) (65yrs ± 6) and controls (n=10) (58yrs ± 9) underwent 4D-Flow MRI to calculate helicity (Figure 1A). The helicity was calculated in 2 segments: 1) the main pulmonary artery (MPA) and 2) along the RV outflow tract (RVOT) - MPA axis. Main pulmonary arterial stiffness was measured using the relative area change (RAC). Results: COPD patients had decreased helicity relative to healthy controls in the MPA (19.4±7.8 vs 32.8±15.9 s -2 , P=0.007) (Figure 1B). Additionally, COPD patients had reduced helicity along the RVOT-MPA axis (33.2±9.0 vs 43.5±8.3 s -2 , P=0.010). The helicity measured in the MPA was associated with RV end-systolic volume (R=0.59, P = 0.002), RVEF (R=0.631, P Conclusion: Patients with COPD show quantitatively abnormal flow hemodynamics, when compared with healthy controls, as assessed by 4D-Flow MRI. A strong association between helicity along the MPA-RV outflow tract axis and RV function suggests that 4D-Flow MRI might be a sensitive tool in evaluating RV - pulmonary arterial coupling in COPD.

Introduction: Idiopathic Pulmonary Arterial Hypertension (PH-Type I) and PH due to pulmonary disease (PH-Type III) arise from different pathophysiologic processes, yet they both culminate in increased right ventricular (RV) afterload and eventual RV failure. Previous work has demonstrated that 4D-Flow MRI-derived intracardiac vorticity (ω) correlates with markers of ventricular interdependency and diastolic dysfunction in PH. However, no investigation has attempted to use both ω and standard markers of ventricular function to phenotype PH subgroups. Hypothesis: 4D-Flow MRI can detect differences in diastolic dysfunction that make it possible to phenotype patients with Type I and Type III PH. Methods: Type I PH patients (n=12, mean age 61yrs), Type III PH patients (n=15, mean age 63yrs), and healthy controls (n=10, mean age 58yrs) underwent standard cardiac MRI as well as 4D-Flow MRI to determine RV intracardiac flow markers including early (ω-E) and late (ω-A) diastolic vorticity. Standard MRI-based RV and LV size and function markers were also collected. Results: ω-E was decreased in the Type I PH group compared to the Type III PH group (P=0.035) and to controls (P Conclusion: Our results indicate that 4D-Flow MRI can distinguish among different PH subtypes using intracardiac diastolic vorticity. Comparative studies with standard echocardiography and catheterization are necessary to assess the sensitivity of 4D-Flow MRI to detect diastolic dysfunction.

Introduction: Cardiovascular disease (CVD) is the leading cause of mortality in patients with type 1 diabetes (T1D). There is increasing evidence that maladaptive changes in vascular properties occur early in adolescence. Wall shear stress (WSS) plays crucial role in mechanotransduction and tissue remodeling. However, changes in aortic WSS and vascular properties in T1D adolescents and their associations with T1D biomarkers have yet to be determined. Hypothesis: We hypothesized that non-invasively MRI derived WSS and vascular markers of stiffness will be altered in T1D adolescents. Methods: Fourteen adolescents with T1D and 25 age-matched controls underwent prospective phase-contrast MRI (PC-MRI). Segmented cross sectional planes were selected above the sinotubular junction, transverse to the descending aorta. Maximum WSS values were computed from time specific generated shear fields. Aortic strain (AoS), distensibility (Ds), and stiffness index β (SI) were computed using vessel areas and pulse pressure. All measured hemodynamic and vascular markers were correlated with standard T1D biomarkers: A1C hemoglobin, cholesterol, LDL, HDL, and triglyceride levels. The significance between reported median values was assessed using Wilcoxon Ranked sum method and single linear regression analysis using Spearman rho. Results: Subjects with T1D showed significantly increased maximum WSS (dyne/cm2) in both ascending aorta (11.1 vs. 9.02, p = 0.0065) and descending aorta (13.7 vs. 12.3, p = 0.0166). Furthermore, AoS and Ds (mmHg-1) were both decreased in T1D group in ascending aorta (AoS: 25.1 vs. 29.7, p = 0.0352; Ds: 0.49 vs. 0.71, p = 0.0151) and descending aorta (AoS: 20.1 vs. 26.5, p = 0.0002; Ds: 0.41 vs. 0.66, p = 0.0082). Inversely, SI was higher in T1D group in both vessel segments (0.030 vs. 0.018, p = 0.0021 and 0.034 vs. 0.020, p = 0.0017). There were no significant correlations between PC-MRI derived vascular metrics and collected biomarkers. Conclusions: T1D adolescents show early aortic stiffness and altered WSS. Neither WSS nor stiffness markers correlated with A1C hemoglobin or lipid biomarkers. This suggests that potential therapeutic targets of the early vascular remodeling are beyond standard glycemic and lipid control.

Introduction: Although pulmonary arterial hypertension (PAH) has significant impact on flow and tissue remodeling in the pulmonary vasculature, previous studies indicate that PAH is also associated with increased stiffness and endothelial dysfunction in the systemic circulation. Alterations in vascular properties of the systemic circulation may have hemodynamic relevance for left ventricular adaptation to PAH. Reduced wall shear stress (WSS) and vascular elastic markers are known manifestations of vascular disease and may provide insight into the vascular behavior of the systemic circulation in PAH. Hypothesis: We hypothesized that WSS and mechanical elasticity are altered in the thoracic aorta in PAH, and that these measures correlate with pulmonary hemodynamics. Methods: As part of a prospective study, 18 patients with PAH and 5 age-matched controls underwent the same day right heart catheterization (RHC) and 4 dimensional flow cardiac magnetic resonance (4D CMR) for computation of WSS in four aortic regions (endovascular landing zones 1 to 4). The aortic capacitance was calculated as the ratio of stroke volume (SV) and pulse pressure (PP). The elastic modulus was defined as the inverse aortic strain divided by PP. The difference in median values was assessed via Wilcoxon ranked sum method and Spearman rho was used for linear regression analysis. Results: The WSS (N/m2) was significantly reduced in all four aortic zones (zone 1: 0.540 vs. 0.800, p = 0.0325; zone 2: 0.424 vs. 0.615, p = 0.0402; zone 3: 0.419 vs. 0.625, p = 0.0250; zone 4: 0.513 vs. 0.794, p = 0.0046). While aortic capacitance (mL/mmHg) was significantly reduced in the PAH subjects (1.82 vs. 5.97, p = 0.008), the elastic modulus (mmHg) was higher (3.52 vs. 8.25, p = < 0.001). The most significant correlation was between the WSS in zone 4 and pulmonary vascular resistance (rho = -0.70, p = 0.006) and mean pulmonary artery pressure (rho = -0.62, p = 0.002). Conclusions: PAH is associated with reduced WSS in the thoracic aorta, suggesting reduced systemic flow conduction in PAH. WSS and mechanical vascular markers may aid in the understanding of the impact of PAH on systemic hemodynamics and tissue mechanics.

Introduction: Pediatric Pulmonary Hypertension (PH) is a degenerative disease that ultimately leads to Right Ventricular (RV) dysfunction. RV functional and biological (e.g. N-Terminal proB-type Natriuretic Peptide, NT-proBNP) phenotypes can provide insight into performance and ventricular distress, respectively. Nevertheless, they are normally considered independently, and should be associated to paint a more comprehensive picture of the cardio-pulmonary system. The most utilized prognostic metric of RV performance is Cardiac Output (CO), as it gives a direct measure of the ventricle’s “pumping” ability. CO is only indicative of the immediate functional state and lacks any predictive or stratification value. RV-Pulmonary Artery (PA) axis decoupling (VVC = RV end-systolic elastance/arterial elastance) represents a decrease in the RV functional reserve, and therefore an inability to accommodate an increase in afterload. Therefore, it is more comprehensive of the entire cardio-pulmonary system than CO. Hypothesis: RV-PA coupling is better associated with NT-proBNP than Cardiac Index (CI = CO/Body Surface Area). Methods: 26 pediatric PH patients underwent Right Heart Catheterization (RHC), an echocardiograph, and blood composition diagnostics. A 0-D model (Fig. 1a) of the comprehensive cardio-pulmonary system, incorporating extensive patient specificity, was developed to estimate RV pressure-volume curves under baseline and challenged conditions, and approximate the VVC ratio. Results: CI was not found to be statistically associated with NT-proBNP (Fig. 1b). Nevertheless, VVC was found to be non-linearly related to NT-proBNP expression (Fig. 1c), thus rejecting the null hypothesis . Conclusion: NT-proBNP is a biomarker of RV-PA functional decoupling. Considering the inter-compartmental interaction of the entire cardio-pulmonary system offers a better picture of PH disease progression then assessing RV “pump” performance.

Introduction: Pulmonary vascular stiffness (PVS) is increasingly recognized as an important component of right ventricular afterload in patients with pulmonary arterial hypertension (PAH). In adult and pediatric PAH populations, stiffness has also been shown to improve prediction of mortality and outcomes, respectively. Despite these promising findings, methods to determine PVS clinically remain limited. Here we examine the ability of a minimally-invasive method to quantify proximal PVS in a pediatric PAH population, and hypothesize this measurement will offer better disease outcomes prediction over indexed pulmonary vascular resistance (PVRI), the current gold standard. Methods: Color M-mode Tissue Doppler Images of the right pulmonary artery (RPA) were obtained using ultrasound during right-heart catheterization of 36 individuals undergoing reactivity testing (n=86) who ranged in age from 1 month to 19 yrs (mean = 6.5±5.2 yrs, 19 males). These measurements yielded RPA diameter and intravascular pressure, from which an estimate of the circumferential elastic (Young’s) modulus (E), the continuum component of stiffness, was derived. Echo imaging added only 5 minutes to the procedure. Follow up was obtained in 19 patients (mean = 4.9±4.7 yrs, range 1 month to 16 yrs, 9 males) at a median time of 15 months (range 1–26 months). Cumulative logistic regression was used to relate continuous values of E and PVRI to three outcomes categories: improvement; stable (no change); or worsening. These were determined from change in WHO score from initial assessment to follow up. Results: E had better correlation to pulse pressure (PP) (R2=0.61) compared to mean pressure (R2=0.43); this agrees with other findings of PP as a good proxy of stiffness. E displayed substantially better correlation (R2L=0.49) to outcomes compared to PVRI (R2L=0.33). In more practical terms, E wrongly predicted outcome only once (5%), compared to four errors by PVRI (21%), and offered clearer prognosis in an additional 3 individuals; thus 37% of the group would benefit from such improved prediction. Conclusion: We conclude that elastic modulus is a measure of proximal vascular stiffening and most importantly offers superior outcomes prediction compared to pulmonary vascular resistance.