Ventricular Pressure Load Research Articles

Research progress on bioinformatics in pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a severe disease characterized by abnormal pulmonary vascular remodeling and increased right ventricular pressure load, posing a significant threat to patient health. While some pathological mechanisms of PAH have been revealed, the deeper mechanisms of pathogenesis remain to be elucidated. In recent years, bioinformatics has provided a powerful tool for a deeper understanding of the complex mechanisms of PAH through the integration of techniques such as multi-omics analysis, artificial intelligence, and Mendelian randomization. This review focuses on the bioinformatics methods and technologies used in PAH research, summarizing their current applications in the study of disease mechanisms, diagnosis, and prognosis assessment. Additionally, it analyzes the existing challenges faced by bioinformatics and its potential applications in the clinical and basic research fields of PAH in the future.

Evaluation of right heart function changes in patients with pulmonary hypertension via two-dimensional speckle tracking imaging: a retrospective study

Objective: To realize the changes in pulmonary hypertension (PH) patients’ right ventricular function.Methods: A total number of 74 patients with PH were included, and the parameters of standard echocardiographic were measured as well as the strain of peak longitudinal of each segment during the systole of the right ventricle to calculate the global longitudinal strain (LS) during systole of the right ventricular free wall.Results: ① As pulmonary arterial pressure increased, the right ventricular area gradually increased, and the case group showed the decreased right ventricular fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), and tricuspid annular peak systolic velocity (S’) (p < 0.05). They, RVFAC, and TAPSE depicted significant differences that were statistical (p < 0.05) from the other groups. ② With increasing pulmonary arterial pressure, the right ventricular free wall’s LS gradually reduced (p < 0.05).Conclusion: ① LS right ventricular free wall is useful in detecting changes in right ventricular systolic function early on with greater sensitivity than RVFAC, TAPSE, and S’. In addition, increased right ventricular pressure loading can result in a subsequent impairment of right ventricular myocardial mechanics. ② As right ventricular pressure loading increases, right ventricular strain decreases. ③ In mild PH, the right ventricular free wall’s. LS is more sensitive than standard measures in spotting early alterations in myocardial mechanics.

NT-proBNP levels as a predictor of higher left ventricular end-diastolic pressure in children with small perimembranous ventricular septal defect

The decision to close small ventricular septal defect is still controversial. Previous study showed that ventricular dysfunction in adulthood is correlated with small perimembranous ventricular septal defect. N terminal pro B-type natriuretic peptide (NT-proBNP) is a neurohormone secreted primarily from the ventricles in response to increased left and right ventricular pressure and volume load. The left ventricular end-diastolic pressure will reflect ventricular performance. This study aimed to evaluate the correlation between left ventricular end-diastolic pressure and the NT-proBNP in children with small perimembranous ventricular septal defect. Level of NT-proBNP in 41 patients with small perimembranous ventricular septal defect was measured before transcatheter closure procedure. We also measured the left ventricular end-diastolic pressure in each patients during catheterisation. We investigated the value of NT-proBNP in patients with small perimembranous ventricular septal defect and its correlation with the level of left ventricular end-diastolic pressure. We found positive correlation between NT-proBNP and left ventricular end-diastolic pressure (r = 0.278, p = 0.046). The median of NT-proBNP at left ventricular end-diastolic pressure < 10 was lower than at left ventricular end-diastolic pressure ≥ 10 (0.87 ng/ml versus 1.83 ng/ml, p = 0.023). The results of the NT-proBNP diagnostic test for predicting left ventricular end-diastolic pressure ≥ 10 using Receiver Operating Characteristic (ROC) analysis showed the area under the curve value of 0.715 (95% CI: 0.546-0.849). The cut-off value >0.99 ng/ml of NT-proBNP has 75.0% sensitivity and 72.2% specifity. Level of NT-proBNP higher than 0.99 ng/ml was correlated significantly with left ventricular end-diastolic pressure ≥10 in children with small perimembranous ventricular septal defect.

Impact of hybrid procedure on pulmonary arterial dimensions and right ventricular load after biventricular repair

BackgroundHybrid procedure with ductal stenting and bilateral pulmonary banding offers a temporary approach in high-risk neonates with complex congenital heart defects aiming biventricular repair. This procedure may also have negative impact concerning post-banding pulmonary stenosis resulting in right ventricular pressure load.MethodsBetween 2010 and 2021 we identified 5 patients with interrupted aortic arch and complex congenital heart defect who underwent hybrid procedure and staged biventricular repair (“hybrid-group”). Other 7 cases with interrupted aortic arch were corrected in the neonatal phase without hybrid procedure (“nonhybrid-group”). Detailed intra- and extracardiac features and surgical procedures were documented as well as pulmonary interventions during follow up. Pulmonary vessel size was assessed by diameter of left and right pulmonary artery in absolute and indexed values. RV pressure was evaluated invasively via catheterization.ResultsSurvival in cases with hybrid procedure and staged biventricular repair was 91% for a follow-up time of 40.7 months (95% CI 26–55 months) and 100% in the non-hybrid-group. Postoperative results concerning left ventricular function showed normal LV dimensions and systolic function without relevant stenosis on distal aortic arch. Hybrid procedure was associated with impaired local pulmonary arterial diameter after debanding resulting in increased right ventricular pressure and need for interventions (number intervention per patient: hybrid group 1.7 ± 0.95, non-hybrid group 0.17 ± 0.41; P 0.003).ConclusionsHybrid procedure in high-risk cases with interrupted aortic arch and staged biventricular repair shows good postoperative results with low perioperative mortality and normal left ventricular function. Due to potential risk of relevant pulmonary stenosis and right ventricular pressure load, follow up examinations must not only focus on left but also on the right heart.Graphical

Reversal of right ventricular pressure loading improves function independent of fibrosis.

Reversal of right ventricular pressure loading improves function independent of fibrosis.

Right ventricular longitudinal function is linked to left ventricular filling pressure in patients with repaired tetralogy of fallot

Experimental data on pulmonary regurgitation has linked right ventricular longitudinal function to left ventricular filling pressure in animals with induced and treated pulmonary regurgitation but this relationship has not been investigated in patients with repaired Tetralogy of Fallot (rToF). The aim of this study was to determine if right ventricular longitudinal function assessed using cardiovascular magnetic resonance (CMR) is associated with left ventricular filling pressure in patients with rToF. A second objective of this study was to determine if direction of septal movement is related to right ventricular pressure load in rToF. Eighteen patients with rToF undergoing CMR and heart catheterization prior to pulmonary valve replacement were retrospectively included and catheter-based pressure measurements were compared with CMR-derived RV regional function. Left ventricular filling pressure was measured as precapillary wedge pressure (PCWP). Longitudinal contribution to RV stroke volume correlated with PCWP (r = 0.48; p = 0.046) but not with RV EF or pulmonary regurgitation. Neither RV longitudinal strain nor TAPSE showed correlation with PCWP. Longitudinal contribution to stroke volume was lower for the RV compared to the LV (49 vs 54%; p = 0.039). Direction of septal movement did not show a correlation with RV end-systolic pressure. Right ventricular longitudinal pumping is associated with left ventricular filling pressure in rToF-patients and this inter-ventricular coupling may explain LV underfilling in patients with pulmonary regurgitation and rToF and may be of value to determine right ventricular dysfunction. RV systolic pressure, however, cannot be assessed from the direction of septal movement, in these patients.

Reversal of right ventricular pressure loading improves biventricular function independent of fibrosis in a rabbit model of pulmonary artery banding.

Right ventricular (RV) pressure loading leads to RV and left ventricular (LV) dysfunction through RV hypertrophy, dilatation and fibrosis. Relief of RV pressure load improves RV function. However, the impact and mechanisms on biventricular reverse-remodelling and function are only partially characterized. We evaluated the impact of RV pressure overload relief on biventricular remodelling and function in a rabbit model of reversible pulmonary artery banding (PAB). Rabbits were randomized to three groups: (1) Sham-operated controls (n=7); (2) PAB (NDef, n=7); (3) PAB followed by band deflation (Def, n=5). Sham and NDef animals were sacrificed at 6weeks after PAB surgery. Def animals underwent PAB deflation at 6weeks and sacrifice at 9weeks. Biventricular geometry, function, haemodynamics, hypertrophy and fibrosis were compared between groups using echocardiography, magnetic resonance imaging, high-fidelity pressure-tipped catheters and histology. RV pressure loading caused RV dilatation, systolic dysfunction, myocyte hypertrophy and LV compression which improved after PAB deflation. RV end-diastolic pressure (RVEDP) decreased after PAB deflation, although remaining elevated vs. Sham. LV end-diastolic pressure (LVEDP) was unchanged following PAB deflation. RV and LV collagen volumes in the NDef and Def group were increased vs. Sham, whereas RV and LV collagen volumes were similar between NDef and Def groups. RV myocyte hypertrophy (r=0.75, P<0.001) but not collagen volume was related to RVEDP. LV myocyte hypertrophy (r=0.58, P=0.016) and collagen volume (r=0.56, P=0.031) correlated with LVEDP. In conclusion, relief of RV pressure overload improves RV and LV geometry, hypertrophy and function independent of fibrosis. The long-term implications of persistent fibrosis and increased biventricular filling pressures, even after pressure load relief, need further study. KEY POINTS: Right ventricular (RV) pressure loading in a pulmonary artery banding rabbit model is associated with RV dilatation, left ventricular (LV) compression; biventricular myocyte hypertrophy, fibrosis and dysfunction. The mechanisms and impact of RV pressure load relief on biventricular remodelling and function has not been extensively studied. Relief of RV pressure overload improves biventricular geometry in conjunction with improved RV myocyte hypertrophy and function independent of reduced fibrosis. These findings raise questions as to the importance of fibrosis as a therapeutic target.

Female rats are less prone to clinical heart failure than male rats in a juvenile rat model of right ventricular pressure load.

Sex is increasingly emerging as determinant of right ventricular (RV) adaptation to abnormal loading conditions. It is unknown, however, whether sex-related differences already occur in childhood. Therefore, this study aimed to assess sex differences in a juvenile model of early RV pressure load by pulmonary artery banding (PAB) during transition from pre to postpuberty. Rat pups (n = 57, 3 wk old, 30-45 g) were subjected to PAB or sham surgery. Animals were euthanized either before or after puberty (4 and 8 wk postsurgery, respectively). Male PAB rats demonstrated failure to thrive already after 4 wk, whereas females did not. After 8 wk, female PAB rats showed less clinical symptoms of RV failure than male PAB rats. RV pressure-volume analysis demonstrated increased end-systolic elastance after 4 wk in females only, and a trend toward preserved end-diastolic elastance in female PAB rats compared with males (P = 0.055). Histology showed significantly less RV myocardial fibrosis in female compared with male PAB rats 8 wk after surgery. Myosin heavy chain 7-to-6 ratio switch and calcineurin signaling were less pronounced in female PAB rats compared with males. In this juvenile rat model of RV pressure load, female rats appeared to be less prone to clinical heart failure compared with males. This was driven by increased RV contractility before puberty, and better preservation of diastolic function with less RV myocardial fibrosis after puberty. These findings show that RV adaptation to increased loading differs between sexes already before the introduction of pubertal hormones.NEW & NOTEWORTHY In this study, we describe sex differences in our unique weanling rat model of increased RV pressure load by pulmonary artery banding. We are the first to assess temporal sex-related differences in RV adaptation during pubertal development. Female rats show superior RV function and less diastolic dysfunction and fibrosis compared with male rats. These differences are already present before puberty, indicating that the differences in RV adaptation are not only determined by sex hormones.

Impact of Right Ventricular Pressure Load After Repair of Tetralogy of Fallot.

BackgroundRight ventricular outflow tract (RVOT) stenosis after repair of tetralogy of Fallot has been linked with favorable right ventricular remodeling but adverse outcomes. The aim of our study was to assess the hemodynamic impact and prognostic relevance of right ventricular pressure load in this population.Methods and ResultsA total of 296 patients with repaired tetralogy of Fallot (mean age, 17.8±7.9 years) were included in a prospective cardiovascular magnetic resonance multicenter study. Myocardial strain was quantified by feature tracking technique at study entry. Follow‐up, including the need for pulmonary valve replacement, was assessed. The combined end point consisted of ventricular tachycardia and cardiac death. A higher echocardiographic RVOT peak gradient was significantly associated with smaller right ventricular volumes and less pulmonary regurgitation, but lower biventricular longitudinal strain. During a follow‐up of 10.1 (0.1–12.9) years, the primary end point was reached in 19 of 296 patients (cardiac death, n=6; sustained ventricular tachycardia, n=2; and nonsustained ventricular tachycardia, n=11). A higher RVOT gradient was associated with the combined outcome (hazard ratio [HR], 1.03; 95% CI, 1.00–1.06; P=0.026), and a cutoff gradient of ≥25 mm Hg was predictive for cardiovascular events (HR, 3.69; 95% CI, 1.47–9.27; P=0.005). In patients with pulmonary regurgitation ≥25%, a mild residual RVOT gradient (15–30 mm Hg) was not associated with a lower risk for pulmonary valve replacement.ConclusionsHigher RVOT gradients were associated with less pulmonary regurgitation and smaller right ventricular dimensions but were related to reduced biventricular strain and emerged as univariate predictors of adverse events. Mild residual pressure gradients did not protect from pulmonary valve replacement. These results may have implications for the indication for RVOT reintervention in this population.

To treat or not to treat pulmonary arteries: epinephrine provocation to unmask right ventricular load

BackgroundPulmonary artery stenosis (PAS) is common in congenital heart disease (CHD). The indication for treatment of PAS is primarily based on invasively measured pressure gradients. Anesthetics used during cardiac catheterization cause systemic and pulmonary hypotension. We hypothesize that this leads to underestimation of right ventricular (RV) pressure load and under treatment of PAS. The aim of this study is to describe the use of epinephrine to unmask RV pressure load in patients with PAS. MethodsAll cardiac catheterizations in which epinephrine was administered to evaluate RV load were included. There was an indication for treatment in case of a right to left ventricular (RV:LV) pressure ratio >0.6. The indication for treatment before and after epinephrine was evaluated to determine its role in clinical decision making. ResultsA total of 74 procedures were included. In all procedures the invasively measured LV pressure was below the awake blood pressure. At baseline, 33 patients had a RV:LV ratio >0.6. In 41 patients the baseline RV:LV ratio was <0.6. After epinephrine bolus, the LV pressure was raised up to the awake blood pressure. In 19 of the 41 patients without baseline indication, this resulted in a RV:LV ratio >0.6 thereby revealing the indication for treatment. No epinephrine related complications were registered. ConclusionThe hypotensive properties of anesthetics during cardiac catheterization may lead to underestimation of RV pressure load. Invasive pressure measurements should be performed under conditions similar to awake conditions. Epinephrine provocation prevented under treatment in 25% of our patients.

Cardiac Remodeling and Disease Progression in Patients With Repaired Coarctation of Aorta and Aortic Stenosis.

Valvulo-arterial impedance (Zva) is used for assessment of left ventricular (LV) global pressure load in patients with aortic stenosis (AS) and impaired arterial compliance. Because patients with repaired coarctation of aorta (COA) have impaired arterial compliance, we hypothesized that COA patients with greater than or equal to moderate AS (AS-COA group) will have higher Zva, symptomatic progression, and cardiovascular events, as compared to non-COA patients with similar AS severity (AS group). Propensity matching (1:1) of 71 AS-COA and 71 AS patients based on age, sex, body mass index, and aortic valve mean gradient (cohort 1). Of 172 patients, 117 patients (AS-COA [n=62]; AS [n=55]) underwent aortic valve replacement, cohort 2. Cohort 1 was used to assess the relationship between preoperative Zva, cardiac remodeling, and symptomatic progression, while cohort 2 was used to assess the relationship between postoperative Zva, LV mass index regression (reduction in LV mass index after aortic valve replacement), and cardiovascular events. The AS-COA group had higher Zva (4.2±0.6 versus 3.5±0.4 mm Hg/mL·m2, P<0.001), more advanced cardiac remodeling, and higher 5-year incidence of symptomatic progression (85% versus 51%, P<0.001). Preoperative Zva was independently associated with cardiac remodeling (r=0.66, P<0.001) and symptomatic progression (hazard ratio, 1.06 [1.02-1.10], per mm Hg/mL·m2 increase in Zva). The AS-COA group had higher postoperative Zva (3.3±0.5 versus 2.4±0.4 mm Hg/mL·m2, P<0.001), less robust LV mass index regression at 1-year post-aortic valve replacement, and higher 5-year incidence of cardiovascular events. Postoperative Zva was independently associated with LV mass index regression (r=-0.46, P<0.001) and cardiovascular events (hazard ratio, 1.06 [1.02-1.10], per mm Hg/mL·m2 increase in Zva). Adults with AS-COA had higher LV global pressure load, cardiac remodeling, symptomatic progression, and cardiovascular events as compared to non-COA patients with similar severity of AS. Zva can identify patients at risk for adverse outcomes, and perhaps should be used for risk stratification with regards to timing of aortic valve replacement.

Abstract 10305: Cardiac Remodeling and Disease Progression in Patients with Repaired Coarctation of Aorta and Aortic Stenosis

Introduction: Valvuloarterial impedance (Zva) is used for assessment of left ventricular (LV) global pressure load in patients with aortic stenosis (AS) and impaired arterial compliance. Since patients with coarctation of aorta (COA) have impaired arterial compliance, we hypothesized that COA patients with ≥moderate AS (AS-COA group) will have higher Zva, symptomatic progression, and cardiovascular events, as compared to non-COA patients with similar AS severity (AS group). Methods: 1:1 propensity matching of 71 AS-COA and 71 AS patients based on age, sex, body mass index, and aortic valve mean gradient. Results: The AS-COA group had higher Zva (4.2±0.6 vs 3.5±0.4 mmHg/ml*m 2 , p&lt;0.001), more advanced cardiac remodeling, and higher 5-year incidence of symptomatic progression (85% vs 51%, p&lt;0.001). Pre-operative Zva was independently associated with cardiac remodeling (r=0.66, p&lt;0.001) and symptomatic progression (HR 1.08, 1.05-1.12, per mmHg/ml*m 2 increase in Zva). Of 172 patients, 117 underwent aortic valve replacement (AVR). The AS-COA group had higher residual Zva(3.3±0.5 vs 2.4±0.4 mmHg/ml*m 2 , p&lt;0.001), less robust LV mass index (LVMI) regression at 1-year post-AVR, and higher 5-year incidence of cardiovascular events. Post-operative Zva was independently associated with LVMI regression (r=-0.46, p&lt;0.001) and cardiovascular events (HR 1.06, 1.02-1.10, per mmHg/ml*m 2 increase in Zva). Conclusions: Adults with repaired COA repair and moderate-severe AS had higher LV global pressure load, cardiac remodeling, symptomatic progression, and cardiovascular events as compared to non-COA patients with similar severity of AS. Zva can identify patients at risk for adverse outcomes, and perhaps should be used for risk stratification with regards to timing of AVR.

Abstract 9973: Combined Inhibition of Transforming-Growth Factorβ1 and Platelet-Derived Growth Factor Receptor Improves Right Ventricular Fibrosis and Diastolic Function in Experimental Right Ventricular Pressure-Loading

Background: Residual lesions in repaired tetralogy of Fallot and other congenital heart diseases induce chronic right ventricular (RV) pressure and/or volume loading. These activate cardiac fibroblasts (CFs) resulting in pathological myocardial remodelling, including fibrosis, contributing to eventual RV diastolic dysfunction, failure, and mortality. Transforming growth factor (TGF)β1 and platelet-derived growth factor (PDGF) are implicated in generating a hyper-fibrotic response to ventricular pressure-loading through synergistic activation and proliferation of CFs. Hypothesis: Dual TGFβ1 and PDGF inhibition will effectively reduce fibrosis in response to RV pressure-loading and thereby improve RV function. Methods: Sprague-Dawley rats underwent pulmonary artery banding (PAB) to induce RV pressure-loading or sham surgery (n=10-12/group). One-week post-PAB, rats were randomized to Tranilast (TRN), a dual TGFβ1/ PDGF inhibitor treatment, (300mg/kg/day, p.o.) or vehicle (n=10-12/group) for 5-weeks. Catheter hemodynamics were measured prior to tissue collection. Results: Preliminary hemodynamic measurements (n=8-10/group) showed similar mean RV/LV pressure ratio (PAB Vehicle 0.8±0.22 vs. PAB TRN 0.81±0.23), +dP/dT, and -dP/dT in PAB groups. PAB TRN rats demonstrated improved end-diastolic pressure (7.0±1.7mmHg vs. 8.59±3.0mmHg), tau (24.15±9ms vs. 31.26±16.5ms), and end-systolic elastance (0.084±0.038mmHg/μL vs. 0.1139±0.057mmHg/μL) compared to PAB vehicle. These were associated with reduced RV collagen deposition (6.5±2.3% vs. 10±5.1%, p&lt;0.05), hypertrophy (Fulton ratio 0.46±0.11 vs. 0.61±0.14, p=0.001), and cardiomyocyte area (921.4±131.7μm 2 vs. 1141±168.7μm 2 , p=0.003), when compared to PAB vehicle-treated controls. Immunoblotting (n=5-6/group) demonstrated reduced RV PDGFRβ expression and SMAD2/3 activation (phosphorylation), despite similar TGFβ1 levels in TRN-treated PAB rats vs. controls. Conclusion: Attenuation of TGFβR1 signalling and reduced PDGFRβ expression were associated with reduced fibrosis and hypertrophy and improved RV diastolic function. Combined inhibition of TGFβ1 and PDGF may be a relevant therapeutic target to improve RV diastolic function in RV pressure-loading.

Neuregulin-1 enhances cell-cycle activity, delays cardiac fibrosis, and improves cardiac performance in rat pups with right ventricular pressure load

ObjectivesRight ventricular (RV) failure is a leading cause of death in patients with congenital heart disease. RV failure is kept at bay during childhood. Limited proliferation of cardiomyocytes is present in the postnatal heart. We propose that cardiomyocyte proliferation improves RV adaptation to pressure load (PL). We studied adaptation in response to increased RV PL and the role of increased cardiomyocyte cell cycle activity (CCA) in rat pups growing into adulthood. MethodsWe induced RV PL at day of weaning in rats (3 weeks; 30-40 g) by pulmonary artery banding and followed rats into adulthood (300 g). We performed histological analyses and RNA sequencing analysis. To study the effects of increased cardiomyocyte cell cycle activity, we administered neuregulin-1 (NRG1), a growth factor involved in cardiac development. ResultsPL induced an increase in CCA, with subsequent decline of CCA (sham/PL at 4 weeks: 0.14%/0.83%; P = .04 and 8 weeks: 0.00%/0.00%; P = .484) and cardiac function (cardiac index: control/PL 4 weeks: 4.41/3.29; P = .468 and 8 weeks: 3.57/1.44; P = .024). RNA sequencing analysis revealed delayed maturation and increased CCA pathways. NRG1 stimulated CCA (PL vehicle/NRG1 at 2 weeks: 0.62%/2.28%; P = .003), improved cardiac function (cardiac index control vs vehicle/NRG1 at 2 weeks: 4.21 vs 3.07/4.17; P = .009/.705) and postponed fibrosis (control vs vehicle/NRG1 at 4 weeks: 1.66 vs 4.82%/2.97%; P = .009/.078) in RV PL rats during childhood. ConclusionsRV PL during growth induces a transient CCA increase. Further CCA stimulation improves cardiac function and delays fibrosis. This proof-of-concept study shows that stimulation of CCA can improve RV adaptation to PL in the postnatal developing heart and might provide a new approach to preserve RV function in patients with congenital heart disease.

POS-270 STRUCTURAL AND FUNCTIONAL CARDIOVASCULAR DISEASE IN CHILDREN AND YOUNG ADULTS WITH CKD AND ON DIALYSIS

Cardiovascular disease (CVD) is the most common cause of morbidity and mortality in young people with chronic kidney disease (CKD). Mineral dysregulation is causally linked with calcium and phosphate deposition in the arterial medial layer. It has been suggested that structural changes lead to arterial stiffness, in turn causing increased left ventricular pressure load and left ventricular hypertrophy. Our aim was to examine structural and functional CV changes in CKD stages 4-5 & dialysis patients under 30 years of age (the age up to which bone mineralization occurs).

Echocardiographically-Derived Septal Positional Angle to Gauge Right Ventricular Pressure Load

Echocardiographically-Derived Septal Positional Angle to Gauge Right Ventricular Pressure Load

Asymmetric Regional Work Contributes to Right Ventricular Fibrosis, Inefficiency, and Dysfunction in Pulmonary Hypertension versus Regurgitation

Right ventricular (RV) pressure loading from pulmonary hypertension (PH) and volume loading from pulmonary regurgitation (PR) lead to RV dysfunction, a critical determinant of clinical outcomes, but their impact on regional RV mechanics and fibrosis is poorly characterized. The aim of this study was to test the hypothesis that regional myocardial mechanics and efficiency in RV pressure and volume loading are associated with RV fibrosis and dysfunction. Eight PH, six PR, and five sham-control rats were studied. The PH rat model was induced using Sugen5416, a vascular endothelial growth factor receptor 2 inhibitor, combined with chronic hypoxia. PR rats were established by surgical laceration of the pulmonary valve leaflets. Six (n=4) or 9 (n=4) weeks after Sugen5416 and hypoxia and 12weeks after PR surgery, myocardial strain and RV pressure were measured and RV pressure-strain loops generated. We further studied RV regional mechanics in 11 patients with PH. Regional myocardial work was calculated as the pressure-strain loop area (mm Hg ∙ %). Regional myocardial work efficiency was quantified through wasted work (ratio of systolic lengthening to shortening work). The relation of regional myocardial work to RV fibrosis and dysfunction was analyzed. In rats, PH and PR induced similar RV dilatation, but fractional area change (%) was lower in PH than in PR. RV lateral wall work was asymmetrically higher in PH compared with sham, while septal work was similar to sham. In PR, lateral and septal work were symmetrically higher versus sham. Myocardial wasted work ratio was asymmetrically increased in the PH septum versus sham. Fibrosis in the RV lateral wall, but not septum, was higher in PH than PR. RV fibrosis burden was linearly related to regional work and to measures of RV systolic and diastolic function but not to wasted myocardial work ratio. Patients with PH demonstrated similar asymmetric and inefficient regional myocardial mechanics. Asymmetric RV work and increased wasted septal work in experimental PH are associated with RV fibrosis and dysfunction. Future investigation should examine whether assessment of asymmetric regional RV work and efficiency can predict clinical RV failure and influence patient management.

Potential benefits of ambulatory blood pressure monitoring in coarctation of aorta

Abstract Background Ambulatory blood pressure monitoring (ABPM) is more sensitive than resting BP assessment in detecting hypertension in patients with coarctation of aorta (COA). However, it is not known whether ABPM provides a better measure of left ventricular (LV) pressure load and LV remodeling as compared to resting BP. LV pressure overload is the lynchpin in the pathogenesis of cardiovascular mortality in COA patients, because it leads to LV remodeling, LV dysfunction and heart failure, which sets-the-stage for cardiovascular death. Therefore identifying a sensitive clinical metric that reflects LV pressure load and LV remodeling, is an important step towards optimizing antihypertensive therapy to prevent LV dysfunction and mortality. We hypothesized that ambulatory systolic BP (SBP) has better correlation with arterial load and LV remodeling indices as compared to resting SBP. Methods Our study cohort comprised of adults with isolated COA without significant residual coarctation (Doppler peak velocity ≤2.5 m/sec), aortic or mitral valve disease. All patients underwent BP measurement at rest, followed by ABPM. Arterial load (LV pressure load) was assessed using Doppler-derived effective arterial elastance index (EAI). LV remodeling was assessed using: LV mass index (LVMI), and E/e'. We divided the cohorts into 4 categories (normotensive, masked, white-coat, and overt hypertension). Results Of the 106 patients (male 69 [65%); age 39±11 years), 98 (93%) had prior COA intervention at 6±5 years. Resting SBP was 132±17, daytime ambulatory SBP was 142±16, and nighttime ambulatory SBP was 128±12 mmHg. The mean arterial load and LV remodeling indices were: EAI 3.4±0.8 mmHg/ml·m2, LVMI 106±21 g/m2, and E/e'11±4. Compared to resting SBP, ambulatory SBP had better correlation with EAI, LVMI, and E/e'. EAI, LVMI and E/e' were significantly different between hypertension categories (Figure 1). Conclusions In this study, we demonstrated that ambulatory SBP had better correlations with arterial load and LV remodeling indices as compared to resting SBP. This suggests that ambulatory SBP was a more robust metric of LV pressure overload and remodeling, and can improve detection of vascular stiffness, LV hypertrophy and elevated LV filling pressure as compared to resting SBP. The results of the current study have important clinical implications with regards to initiation and titration of antihypertensive therapy. If ABPM is used as the gold standard for diagnosis of hypertension, the masked hypertension group (who would have been misclassified as normotensive based on resting SBP alone) will qualify for antihypertensive therapy. Additionally, since ambulatory SBP had better correlation with LV remodeling indices, perhaps titration of antihypertensive therapy using ABPM will potentially reduce the risk of LV hypertrophy and dysfunction due to hypertension. Figure 1 Funding Acknowledgement Type of funding source: None

Dynamic right and left ventricular interactions in the pig.

What is the central question of this study? Are the mechanisms that cause ventricular interdependence different when due to primary right to left ventricular pressure loading? What is the main finding and its importance? An instantaneous selective increase in aortic pressure causes an immediate increase in right ventricular end-systolic pressure independent of the pericardium, whereas a selective increase in pulmonary artery pressure decreases left ventricular diastolic compliance owing to a subsequent increasing right ventricular end-diastolic volume as a function of an intact pericardium limiting biventricular volume. Changes in contraction synchrony of either ventricle do not appear to be causing these effects. I characterized the dynamic factors determining ventricular interdependence with and without the pericardium. I measured right (RV) and left ventricular (LV) pressures and volumes simultaneously using conductance catheters in seven pentobarbitone-anaesthetized open-chested 5- to 7-week-old piglets. I studied these effects during apnoea, inferior vena caval occlusion and rapid partial aortic and pulmonary arterial occlusions. Conductance catheter-defined long-axis regional volumes were assessed to define regional contractile synchrony. Closed-pericardium measures were made from an initial (baseline) volume, then after two 20mlkg-1 fluid loads followed by an open-pericardium step. Baseline RV and LV volumes were similar. Aortic occlusion increased LV pressures and volumes and RV end-systolic pressure such that RV end-systolic elastance increased without changes in RV contraction synchrony, not affected by the pericardium. Pulmonary artery occlusion increased RV end-systolic pressure but not end-systolic volume. On the subsequent beat, RV end-diastolic pressure increased, whereas LV end-diastolic volume and diastolic compliance decreased. These effects were attenuated by opening the pericardium. Contraction synchrony across longitudinal segments was unaltered by either aortic or pulmonary artery occlusion. I conclude that the determinants of systolic and diastolic ventricular interdependence are different. Increasing RV pressures causes diastolic RV-to-LV interdependence, decreasing LV diastolic compliance and dependent on an intact pericardium. An increase in LV end-systolic pressure increases RV end-systolic elastance independent of the pericardium and has a minimal effect on RV diastolic function or contraction synchrony.

Speckle tracking echocardiographically-based analysis of ventricular strain in children: an intervendor comparison

BackgroundStrain and synchrony can be calculated from a variety of software packages, but there is a paucity of data with inter-vendor comparisons in children. To test the hypothesis that different packages may affect results, independent of acquisition, we compared values obtained using two commercially available analysis tool (QLAB and TomTec), with several different settings.MethodsThe study population included 108 children; patients were divided into three groups: (1) normal cardiac structure and conduction; (2) ventricular paced rhythm; and (3) flattened ventricular septum (reflecting right ventricular pressure or volume load lesions). We analyzed the same image acquired from the apical 4-chamber (AP4) and short-axis at the mid-papillary level (SAXM) views in both QLAB (versions 10.5 and 10.8) and TomTec (version 1.2). In QLAB version 10.8, low, medium, and high quantification smoothness settings were employed. In TomTec, images were analyzed with both low and high frame rates. Tracking quality for each package was graded. AP4 and SAXM strain and synchrony values were recorded. A mixed-effects linear regression model was used, with main effect considered significant if the p-value was < 0.05.ResultsTracking scores were high for all packages except QLAB 10.5 in the SAXM view. AP4 and SAXM strain values varied significantly between QLAB 10.5 and the other packages. Synchrony values varied widely for all strain values (p < 0.001 for both) in all packages. Quantification smoothness changes in QLAB 10.8 did not impact strain significantly in any patient group; temporal resolution changes in TomTec resulted in strain differences in children with flat ventricular septums, but not those with normal or ventricular paced hearts.ConclusionSynchrony values varied substantially among all packages in children. Strain values varied widely between QLAB 10.5 and all other software packages, recommending avoidance of QLAB 10.5 for future studies. Quantification smoothness settings in QLAB 10.8 resulted in minimal strain differences. In TomTec, low and high frame rate strain values differed only in a subset of patients (flattened septum). These data suggest that reliable comparisons between strain values derived from QLAB and TomTec is possible in certain cases, but that caution should be used especially in different hemodynamics conditions.