scholarly journals Non-invasive imaging of global and regional cardiac function in pulmonary hypertension

2017 ◽  
Vol 8 (1) ◽  
pp. 204589321774200 ◽  
Author(s):  
Tim Crowe ◽  
Geeshath Jayasekera ◽  
Andrew J. Peacock
Keyword(s):  
Pulmonary Hypertension ◽  
Cardiac Function ◽  
Left Ventricular ◽  
Cardiac Response ◽  
Response To Treatment ◽  
Advantages And Disadvantages ◽  
Non Invasive ◽  
Pulmonary Hemodynamic ◽  
Regional Cardiac Function ◽  
Rv Function

Pulmonary hypertension (PH) is a progressive illness characterized by elevated pulmonary artery pressure; however, the main cause of mortality in PH patients is right ventricular (RV) failure. Historically, improving the hemodynamics of pulmonary circulation was the focus of treatment; however, it is now evident that cardiac response to a given level of pulmonary hemodynamic overload is variable but plays an important role in the subsequent prognosis. Non-invasive tests of RV function to determine prognosis and response to treatment in patients with PH is essential. Although the right ventricle is the focus of attention, it is clear that cardiac interaction can cause left ventricular dysfunction, thus biventricular assessment is paramount. There is also focus on the atrial chambers in their contribution to cardiac function in PH. Furthermore, there is evidence of regional dysfunction of the two ventricles in PH, so it would be useful to understand both global and regional components of dysfunction. In order to understand global and regional cardiac function in PH, the most obvious non-invasive imaging techniques are echocardiography and cardiac magnetic resonance imaging (CMRI). Both techniques have their advantages and disadvantages. Echocardiography is widely available, relatively inexpensive, provides information regarding RV function, and can be used to estimate RV pressures. CMRI, although expensive and less accessible, is the gold standard of biventricular functional measurements. The advent of 3D echocardiography and techniques including strain analysis and stress echocardiography have improved the usefulness of echocardiography while new CMRI technology allows the measurement of strain and measuring cardiac function during stress including exercise. In this review, we have analyzed the advantages and disadvantages of the two techniques and discuss pre-existing and novel forms of analysis where echocardiography and CMRI can be used to examine atrial, ventricular, and interventricular function in patients with PH at rest and under stress.

scholarly journals Delineating the molecular and histological events that govern right ventricular recovery using a novel mouse model of pulmonary artery de-banding

2019 ◽  
Vol 116 (10) ◽  
pp. 1700-1709 ◽  
Author(s):  
Mario Boehm ◽  
Xuefei Tian ◽  
Yuqiang Mao ◽  
Kenzo Ichimura ◽  
Melanie J Dufva ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Mouse Model ◽  
Pulmonary Artery ◽  
Right Ventricular ◽  
Exercise Capacity ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Sequence Of Events ◽  
Reverse Remodelling ◽  
Rv Function

Abstract Aims The temporal sequence of events underlying functional right ventricular (RV) recovery after improvement of pulmonary hypertension-associated pressure overload is unknown. We sought to establish a novel mouse model of gradual RV recovery from pressure overload and use it to delineate RV reverse-remodelling events. Methods and results Surgical pulmonary artery banding (PAB) around a 26-G needle induced RV dysfunction with increased RV pressures, reduced exercise capacity and caused liver congestion, hypertrophic, fibrotic, and vascular myocardial remodelling within 5 weeks of chronic RV pressure overload in mice. Gradual reduction of the afterload burden through PA band absorption (de-PAB)—after RV dysfunction and structural remodelling were established—initiated recovery of RV function (cardiac output and exercise capacity) along with rapid normalization in RV hypertrophy (RV/left ventricular + S and cardiomyocyte area) and RV pressures (right ventricular systolic pressure). RV fibrotic (collagen, elastic fibres, and vimentin+ fibroblasts) and vascular (capillary density) remodelling were equally reversible; however, reversal occurred at a later timepoint after de-PAB, when RV function was already completely restored. Microarray gene expression (ClariomS, Thermo Fisher Scientific, Waltham, MA, USA) along with gene ontology analyses in RV tissues revealed growth factors, immune modulators, and apoptosis mediators as major cellular components underlying functional RV recovery. Conclusion We established a novel gradual de-PAB mouse model and used it to demonstrate that established pulmonary hypertension-associated RV dysfunction is fully reversible. Mechanistically, we link functional RV improvement to hypertrophic normalization that precedes fibrotic and vascular reverse-remodelling events.

scholarly journals Non-Invasive Assessment of Left Ventricle Ejection Fraction: Where Do We Stand?

2021 ◽  
Vol 11 (11) ◽  
pp. 1153
Author(s):  
Alessandra Scatteia ◽  
Angelo Silverio ◽  
Roberto Padalino ◽  
Francesco De Stefano ◽  
Raffaella America ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Ejection Fraction ◽  
Systolic Function ◽  
Left Ventricular ◽  
Left Ventricle Ejection Fraction ◽  
Advantages And Disadvantages ◽  
Non Invasive ◽  
Lv Ejection Fraction ◽  
Lv Systolic Function ◽  
Invasive Evaluation

The left ventricular (LV) ejection fraction (EF) is the preferred parameter applied for the non-invasive evaluation of LV systolic function in clinical practice. It has a well-recognized and extensive role in the clinical management of numerous cardiac conditions. Many imaging modalities are currently available for the non-invasive assessment of LVEF. The aim of this review is to describe their relative advantages and disadvantages, proposing a hierarchical application of the different imaging tests available for LVEF evaluation based on the level of accuracy/reproducibility clinically required.

P1783Prognostic implications of significant tricuspid regurgitation in patients with atrial fibrillation in the absence of left-sided heart disease or pulmonary hypertension

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M F Dietz ◽  
E A Prihadi ◽  
P Van Der Bijl ◽  
N Ajmone Marsan ◽  
V Delgado ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Pulmonary Hypertension ◽  
Heart Disease ◽  
Tricuspid Regurgitation ◽  
Left Ventricular ◽  
Right Atrial ◽  
Left Ventricular Ejection ◽  
Event Free Survival ◽  
Free Survival ◽  
Rv Function

Abstract Background Tricuspid regurgitation (TR) can be caused by atrial fibrillation (AF) in the absence of left-sided heart disease or pulmonary hypertension. The prognostic impact of AF-TR has not been investigated. Purpose The aim of this study was to investigate the prognostic significance of TR in AF patients who do not show left-sided heart disease, pulmonary hypertension or primary structural abnormalities. Methods A total of 63 AF patients with moderate and severe TR were identified and matched by age and gender to 116 patients with AF without significant TR, resulting in a total study population of 179 patients (mean age 71±7 years, 59% male). As per design of the study, patients with primary TR, significant (moderate or severe) aortic and/or mitral valve disease, previous valvular surgery, congenital heart disease, left ventricular ejection fraction <50%, systolic pulmonary artery pressure >40mmHg, pacemaker or implantable cardioverter defibrillator leads in situ were excluded as well as patients with AF de novo. Patients were followed for the combined endpoint of all-cause mortality, hospitalization for heart failure and stroke. Results Patients with AF-TR had more often paroxysmal AF as compared to patients without TR (60% vs. 43%, p=0.028). In addition, right atrial volumes and the tricuspid annulus diameter (TAD) were significantly larger in patients with AF-TR compared to their counterparts (p<0.001 for all). Furthermore, tricuspid annular plane systolic excursion was significantly lower in patients with AF-TR (17±5 mm vs. 21±6 mm, p<0.001). During follow-up (median 62 [32–95] months) 55 events for the combined endpoint occurred. One- and 5-year event-free survival rates for patients with TR were 71% and 53%, compared to 92% and 85% for patients without TR, respectively (Log rank Chi-Square p<0.001; Figure). In the multivariable Cox proportional hazard model adjusted for age, gender, NYHA functional class >2, renal function, right ventricular (RV) function and TAD, the presence of significant TR was independently associated with the combined endpoint (HR, 2.495; 95% CI, 1.167–5.335; p=0.018), while RV function was not (HR, 1.026; 95% CI, 0.971–1.085; p=0.364). Figure 1. Kaplan-Meier curves Conclusion In the absence of left-sided heart disease and pulmonary hypertension, significant TR is independently associated with worse event-free survival in patients with AF.

scholarly journals Echocardiographic assessment of right ventricular function in experimental pulmonary hypertension

2019 ◽  
Vol 9 (2) ◽  
pp. 204589401984198 ◽  
Author(s):  
Zhongkai Zhu ◽  
Dureti Godana ◽  
Ailing Li ◽  
Bianca Rodriguez ◽  
Chenxin Gu ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Rat Model ◽  
Cost Effective ◽  
Experimental Models ◽  
Clinical Diagnostics ◽  
Rodent Models ◽  
Ejection Time ◽  
Non Invasive ◽  
Cost Effective Method ◽  
Rv Function

Echocardiography, a non-invasive and cost-effective method for monitoring cardiac function, is commonly used for evaluation and pre-clinical diagnostics of pulmonary hypertension (PH). Previous echocardiographic studies in experimental models of PH are fragmentary in terms of the evaluation of right ventricle (RV) function. In this study, three rodent models of PH: a mouse model of hypoxia-induced PH, a rat model of hypoxia+Sugen induced PH and a rat model of monocrotaline-induced PH, were employed to measure RV fractional area change (RVFAC), RV free wall thickness (RVFWT), pulmonary acceleration time (PAT), pulmonary ejection time (PET), and tricuspid annular plane systolic excursion (TAPSE). We found that, in these models, RVFWT significantly increased, but RVFAC, PAT, or PAT/PET ratios and TAPSE values significantly decreased. Accurate and complete TAPSE patterns were demonstrated in the three rodent models of PH. The RV echocardiography data matched the corresponding invasive hemodynamic and heart histologic data in each model. This serves as a reference study for real-time and non-invasive evaluation of RV function in rodent models of PH using echocardiography.

Increased cholinergic activity under conditions of low estrogen leads to adverse cardiac remodeling

2020 ◽  
Author(s):  
Vanessa P. Teixeira ◽  
Kiany Miranda ◽  
Sergio Scalzo ◽  
Cibele Rocha-Resende ◽  
Mário Morais Silva ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Postmenopausal Women ◽  
Ventricular Myocytes ◽  
Left Ventricular ◽  
Genetically Engineered ◽  
Cardiac Response ◽  
Cholinesterase Inhibition ◽  
Functional Changes ◽  
Concentric Hypertrophy ◽  
The Impact

Cholinesterase inhibitors are used in postmenopausal women for the treatment of neurodegenerative diseases. Despite their widespread use in the clinical practice, little is known about the impact of augmented cholinergic signaling on cardiac function under reduced estrogen conditions. To address this gap, we subjected a genetically engineered murine model of systemic vesicular acetylcholine transporter overexpression (Chat-ChR2) to ovariectomy and evaluated cardiac parameters. Left-ventricular function was similar between Chat-ChR2 and wild-type (WT) mice. Following ovariectomy, WT mice showed signs of cardiac hypertrophy. Conversely, ovariectomized (OVX) Chat-ChR2 mice evolved to cardiac dilation and failure. Transcript levels for cardiac stress markers ANP and BNP were similarly upregulated in WT/OVX and Chat-ChR2/OVX mice. 17β-Estradiol (E2) treatment normalized cardiac parameters in Chat-ChR2/OVX to the Chat-ChR2/SHAM levels, providing a link between E2 status and the aggravated cardiac response in this model. To investigate the cellular basis underlying the cardiac alterations, ventricular myocytes were isolated and their cellular area and contractility were assessed. Myocytes from WT/OVX mice were wider than WT/SHAM, an indicative of concentric hypertrophy, but their fractional shortening was similar. Conversely, Chat-ChR2/OVX myocytes were elongated, and presented contractile dysfunction. E2 treatment again prevented the structural and functional changes in Chat-ChR2/OVX myocytes. We conclude that hypercholinergic mice under reduced estrogen conditions do not develop concentric hypertrophy, a critical compensatory adaptation, evolving towards cardiac dilation and failure. This study emphasizes the importance of understanding the consequences of cholinesterase inhibition, used clinically to treat dementia, for cardiac function in postmenopausal women.

scholarly journals Assessment of left ventricular mechanics in right ventricular overload using in silico rat models

2021 ◽  
Vol 2 (4) ◽  
Author(s):  
H Martinez-Navarro ◽  
E K S Espe ◽  
O O Odeigah ◽  
I Sjaastad ◽  
J Sundnes
Keyword(s):  
Cardiac Function ◽  
Circumferential Strain ◽  
Radial Strain ◽  
Left Ventricular ◽  
Public Institution ◽  
Lv Function ◽  
Passive Stiffness ◽  
Ventricular Mechanics ◽  
Longitudinal Strains ◽  
Rv Function

Abstract Background To preserve cardiac function in overload conditions, the RV adapts by developing muscular hypertrophy through progressive tissue remodelling. This process may lead to a vicious cycle with detrimental effects on RV diastolic and systolic function, as seen in pulmonary arterial hypertension (PAH) patients [1]. However, how RV overload affects LV function and remodelling remains an open question [2]. Computational models of cardiac physiology offer an opportunity for investigating mechanisms difficult or impossible to analyse otherwise due to the existence of overlapping factors and technical limitations. Aim This study aims to assess the acute effects of RV overload and increased myocardial passive stiffness on the LV mechanical properties in an anatomically-based computational model of healthy rat heart. Methods A computational simulation pipeline of cardiac mechanics based on the Holzapfel-Ogden model has been implemented using MR images from a healthy rat. Whereas LV function was modelled realistically using catheter measurements conducted on the same subject than the MR imaging, RV function was based on representative literature values for healthy and PAH rats with RV overload. The following cases were defined (Fig. 1): CTRL, with normal RV function; PAH1, with 30% increase in RV ESV (end-systolic volume) and 15% increase in RV ESP (end-systolic pressure) in comparison to CTRL; and PAH2, with 60% increase in RV ESV and 30% increase in RV ESP compared to CTRL. The cardiac cycle was simulated for all cases whilst fitting the experimentally measured LV pressure and volume values from a healthy rat, which allowed quantifying the effects of RV overload on LV function. Results The increase of average circumferential strain in the LV correlated with the degree of RV overload simulated (CTRL: −8.7%, PAH1: −8.9%, PAH2: −9.2%), whilst average radial (CTRL: 35.2%, PAH1: 34.8%, PAH2: 30.3%) and longitudinal strains decreased (CTRL: −7.7%, PAH1: −7.4%, PAH2: −6.6%), as seen in Fig.2. However, regional differences in strain were significant: under RV overload conditions, circumferential strain increased in the septum (−3.5% difference in PAH2 vs. CTRL) but lower values were observed in the lateral wall (+1.7% difference in PAH2 vs. CTRL). Cardiac function of case PAH2 was simulated also with increased myocardial passive stiffness (2.67 kPa instead of 1.34 kPa) which presented a mild strain increase in the mid LV ventricle in comparison to PAH2 with normal stiffness (circumferential strain: −0.8%, radial strain: +0.5%, longitudinal strain: −0.2%). Conclusion Our study provides mechanistic evidence on how RV overload and increased passive myocardial stiffness causes a redistribution of strain and fibre stress in the LV, which may play a significant role in LV remodelling and function. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): K.G. Jebsen Center for Cardiac Research Figure 1. Pressure – volume loops  Figure 2. Mean mid-LV strains

CILP1 as a biomarker for right ventricular maladaptation in pulmonary hypertension

2020 ◽  
pp. 1901192
Author(s):  
Stanislav Keranov ◽  
Oliver Dörr ◽  
Leili Jafari ◽  
Christian Troidl ◽  
Christoph Liebetrau ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Protein Expression ◽  
Right Ventricular ◽  
Predictive Power ◽  
Pressure Overload ◽  
Serum Levels ◽  
Left Ventricular ◽  
Dilative Cardiomyopathy ◽  
Significant Difference ◽  
Rv Function

The aim of our study was to analyse the protein expression of cartilage intermediate layer protein 1 (CILP1) in a mouse model of right ventricular (RV) pressure overload and to evaluate CILP1 as a biomarker of cardiac remodelling and maladaptive RV function in patients with pulmonary hypertension (PH).Pulmonary artery banding was performed in 14 mice; another 9 mice underwent sham surgery. CILP1 protein expression was analysed in all hearts by western blotting and immunostaining. CILP1 serum concentrations were measured in 161 patients (97 with adaptive and maladaptive RV pressure overload caused by PH; 25 with left ventricular (LV) hypertrophy; 20 with dilative cardiomyopathy (DCM); 19 controls without LV or RV abnormalities)In mice, the amount of RV CILP1 was markedly higher after banding than after sham. Control patients had lower CILP1 serum levels than all other groups (p<0.001). CILP1 concentrations were higher in PH patients with maladaptive RV function than those with adaptive RV function (p<0.001), LV pressure overload (p<0.001), and DCM (p=0.003). CILP1 showed good predictive power for maladaptive RV in ROC analysis (AUC 0.79). There was no significant difference between the AUCs of CILP1 and NT-pro-BNP (AUC 0.82). High CILP1 (≥cut-off value for maladaptive RV of 4373 pg·mL−1) was associated with lower TAPSE/PASP ratios (p<0.001) and higher NT-pro-BNP levels (p<0.001).CILP1 is a novel biomarker of RV and LV pathological remodelling that is associated with RV maladaptation and ventriculoarterial uncoupling in patients with PH.

Abstract 17280: A New in vivo Imaging Protocol for Non-Invasive Detection of Right Ventricular Dysfunction in a Pulmonary Hypertension Mouse Model

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Thomas Hansen ◽  
Kristen Bubb ◽  
Gemma Figtree
Keyword(s):  
Pulmonary Hypertension ◽  
Mouse Model ◽  
Right Ventricular ◽  
Systolic Pressure ◽  
Saline Control ◽  
Novel Therapies ◽  
Imaging Protocol ◽  
Non Invasive ◽  
Rv Function

Introduction: Accurate measurements of right ventricular (RV) function are critical for studying novel therapies impacting the heart and pulmonary circulation. Until now, assessment in mouse models has relied on invasive measures. Improvements in mouse echocardiography may facilitate application of measures recently validated in humans, including tricuspid annular plane systolic excursion (TAPSE) and RV-S’ (systolic excursion velocity), to allow non-invasive assessment of RV function. Aims: To apply and validate TAPSE and RV-S’ using high-resolution echocardiography for the measurement of RV function in a mouse model of pulmonary hypertension (PH). Methods: Echocardiography was performed on mice 3 weeks after induction of PH using inhaled bleomycin or saline control. PAT, TAPSE and RV-S’ were recorded in mice using a 55-mHz transducer (Visualsonics, Vevo3100). Invasive measurements of right ventricular systolic pressure (RVSP) were obtained via catheterisation of the internal jugular vein, prior to culling. Results: RVSP was significantly elevated in bleomycin-treated mice ( 33.41±0.8mmHg n=10) compared to controls ( 25.66±0.9mmHg n=11; p<0.0001). Similarly, RV hypertrophy was observed in bleomycin mice [RV:body weight 1.156±0.03g/kg n=11] compared with control ( 0.968±0.02g/kg n=12; p=0.0002). TAPSE was sensitive to these differences, being significantly reduced in bleomycin mice ( 0.5739±0.020mm n=8) compared with control ( 0.7387±0.033mm n=10; p=0.0012), and correlated significantly with invasive RVSP (r 2 =0.7218; p<0.0001). RV-S’ was also reduced in bleomycin mice (18.14±0.98mm/s n=7) compared with control (25.38±1.24mm/s n=8; p=0.0006) and correlated strongly with RVSP (r 2 =0.6378; p=0.0011). The correlation of both TAPSE and RV-S’ with RVSP compared favourably to the previously used surrogate measure of RVSP in mice, PAT (r 2 =0.5278; p=0.0002). Conclusions: TAPSE and RV-S’ can be applied in mouse echocardiography, and are sensitive, non-invasive measures of PH and RV dysfunction, comparing well with gold-standard invasive right ventricular systolic pressures. This may benefit the power of future preclinical studies of novel therapies in pulmonary hypertension and RV dysfunction.

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