Novel echocardiographic parameters in pulmonary hypertension assessment and the relationship between echocardiography and 6-minute walking test.

Pulmonary artery stiffness (PAS) has been shown to be related to pulmonary artery pressure in patients with pulmonary artery hypertension (PAH). The aim of this study was to determine the correlation between functional capacity and echocardiographic indices of PAS in patients with PAH. This cross-sectional study was performed on patients with PAH who were confirmed by right heart catheterization and referred to Imam Reza PAH clinic for routine follow-up between November 2019 and January 2020. All patients underwent echocardiography and the maximum Doppler frequency shift, pulmonary acceleration time, peak velocity of the pulmonary flow, and velocity time integral, as well as PAS, were measured. All patients performed a 6-minute walk test. Fifty patients with a mean age of 41.90 ±â€…14.73 years old participated in this study. The majority of the patients were female (74%). The most common cause of PAH was idiopathic (74%). There was a significant correlation between PAS and pulmonary artery systolic pressure (r = 0.302, P = .041), second pulmonary valve pulse Doppler velocity (V2) (r = -0.461, P = .003), time from onset of pulmonary flow ejection to V2/first pulmonary valve pulse Doppler velocity (r = -0.311, P = .037) and Z3 ratio (r = -0.346, P = .023). There was no significant correlation between PAS and 6-minute walk test, pulmonary vascular resistance, and tricuspid annular plane systolic excursion (P > .05). There was a significant correlation between V2 and pulmonary vascular resistance (r = 0.359, P = .049). PAS and first pulmonary valve pulse Doppler velocity are simple, noninvasive, available tools for the evaluation of pulmonary vascular beds and diagnosis of presymptomatic clinical status in patients with PAH.

Multiparametric assessment of right ventricular function in heart transplant recipients by echocardiography and relations with pulmonary hemodynamics.

OBJECTIVE: Right ventricular (RV) dilatation and dysfunction are usually present in heart transplant (HTx) patients and worsened with residual pulmonary hypertension (PH). We aimed to determine the ability of different echocardiographic modalities to evaluate RV function in comparison with cardiac magnetic resonance (CMR) and their relations with pulmonary hemodynamics in HTx patients. METHODS: A total of 62 data sets [echocardiographic, hemodynamic, and CMR] were acquired from 35 HTx patients. Comprehensive echocardiography, including two-dimensional (2D) transthoracic echocardiography, speckle tracking echocardiography, and three-dimensional (3D) echocardiography, was performed. Mean pulmonary artery pressure (mPAP) was obtained invasively from right heart catheterization. The correlations between all echocardiographic parameters and CMR imaging data and the differences between patients with and without residual PH were evaluated. RESULTS: Diastolic and systolic RV volumes and RV ejection fraction (RVEF) by 3D echocardiography correlated strongly with CMR-derived volumes and RVEF (r = .91, r = .79, r = .64; p < .0001 for each, respectively). Among other parameters, RV fractional area change (r = .439; p < .001) and RV free wall longitudinal strain (RVFW-LS) (r = -.34; p < .05) correlated moderately with CMR-RVEF, whereas tricuspid annulus S' velocity (r = .29; p < .05) and tricuspid annular systolic plane excursion (r = .27; p < .05) correlated weakly with CMR-RVEF. Additionally, 3D-RVEF and RVFW-LS were significantly decreased in studies with mPAP ≥ 20 mm Hg in comparison to those with mPAP < 20 mm Hg (47.7 ± 3.7 vs. 50.9 ± 5.3, p = .04 and -15.5 ± 3.1 vs. -17.5 ± 3, p = .03, respectively). CONCLUSION: The best method for the evaluation of RV function in HTx recipients is 3D echocardiography. Besides, the subclinical impact of residual PH on RV function can be best determined by RVFW-LS and 3D-RVEF in these patients.

Right ventricular assessment in pulmonary hypertension.

PURPOSE OF REVIEW: The purpose of this review is to provide an overview of assessment of right ventricular function in the context of pulmonary hypertension and pulmonary arterial hypertension (PAH). We will review unique features of right ventricular anatomy, delineation of cause of pulmonary hypertension through careful right ventricular assessment, echocardiographic and hemodynamic evaluation, and the importance of this assessment in prognosis. RECENT FINDINGS: The importance of performance in prognosis and risk assessment in patients with pulmonary hypertension has been continually emphasized in ongoing research. Representative parameters of right ventricular function have been shown to be predictive of prognosis in patients with pulmonary hypertension. Further, the importance of serial right ventricular assessment in risk assessment and prognosis has remained an emerging theme. SUMMARY: Careful evaluation of right ventricular function is paramount in assessing the cause of pulmonary hypertension and severity of disease. Further, it has prognostic significance, as many representative parameters of right ventricular function have been linked with mortality. In our opinion, right ventricular function should be assessed serially throughout the course of treatment in pulmonary hypertension, and baseline parameters in addition to dynamic changes should be incorporated into risk assessment. Achieving normal or near-normal right ventricular performance may serve as a principal goal in the treatment of pulmonary hypertension.

Comprehensive Echocardiographic Assessment of Right Ventricle Function in a Rat Model of Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a progressive disease caused by vasoconstriction and remodeling of the small arteries in the lungs. This remodeling leads to increased pulmonary vascular resistance, worsened right ventricular function, and premature death. Currently approved therapies for PAH largely target pulmonary vasodilator pathways; however, recent emerging therapeutic modalities are focused on other novel pathways involved in the pathogenesis of the disease, including right ventricle (RV) remodeling. Imaging techniques that allow longitudinal assessment of novel therapeutics are very useful for determining the efficacy of new drugs in preclinical studies. Noninvasive trans-thoracic echocardiography remains the standard approach to evaluating heart function and is widely used in rodent models. However, echocardiographic evaluation of the RV can be challenging due to its anatomical position and structure. In addition, standardized guidelines are lacking for echocardiography in preclinical rodent models, making it difficult to carry out a uniform assessment of RV function across studies in different laboratories. In preclinical studies, the monocrotaline (MCT) injury model in rats is widely used to evaluate drug efficacy for treating PAH. This protocol describes the echocardiographic evaluation of the RV in naïve and MCT-induced PAH rats.

Quantitative Assessment of Regional Pulmonary Transit Times in Pulmonary Hypertension.

BACKGROUND: Pulmonary hypertension (PH) contributes to restricted flow through the pulmonary circulation characterized by elevated mean pulmonary artery pressure acquired from invasive right heart catheterization (RHC). MRI may provide a noninvasive alternative for diagnosis and characterization of PH. PURPOSE: To characterize PH via quantification of regional pulmonary transit times (rPTT). STUDY TYPE: Retrospective. POPULATION: A total of 43 patients (58% female); 24 controls (33% female). RHC-confirmed patients classified as World Health Organization (WHO) subgroups 1-4. FIELD STRENGTH/SEQUENCE: A 1.5 T/time-resolved contrast-enhanced MR Angiography (CE-MRA). ASSESSMENT: CE-MRA data volumes were combined into a 4D matrix (3D resolution + time). Contrast agent arrival time was defined as the peak in the signal-intensity curve generated for each voxel. Average arrival times within a vessel region of interest (ROI) were normalized to the main pulmonary artery ROI (t0 ) for eight regions to define rPTT for all subjects. Subgroup analysis included grouping the four arterial and four venous regions. Intraclass correlation analysis completed for reproducibility. STATISTICAL TESTS: Analysis of covariance with age as covariate. A priori Student's t-tests or Wilcoxon rank-sum test; α = 0.05. Results compared to controls unless noted. Significant without listing P value. ICC ran as two-way absolute agreement model with two observers. RESULTS: PH patients demonstrated elevated rPTT in all vascular regions; average rPTT increase in arterial and venous branches was 0.85 ± 0.15 seconds (47.7%) and 1.0 ± 0.18 seconds (16.9%), respectively. Arterial rPTT was increased for all WHO subgroups; venous regions were elevated for subgroups 2 and 4 (group 1, P = 0.86; group 3, P = 0.32). No significant rPTT differences were found between subgroups (P = 0.094-0.94). Individual vessel ICC values ranged from 0.58 to 0.97. DATA CONCLUSION: Noninvasive assessment of PH using standard-of-care time-resolved CE-MRA can detect increased rPTT in PH patients of varying phenotypes compared to controls. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 3.

Optical coherence tomography assessment of pulmonary vascular remodeling in advanced heart failure. The OCTOPUS-CHF study.

INTRODUCTION AND OBJECTIVES: Pulmonary vascular remodeling is common among patients with advanced heart failure. Right heart catheterization is the gold standard to assess pulmonary hypertension, but is limited by indirect measurement assumptions, a steady-flow view, load-dependency, and interpretation variability. We aimed to assess pulmonary vascular remodeling with intravascular optical coherence tomography (OCT) and to study its correlation with hemodynamic data. METHODS: This observational, prospective, multicenter study recruited 100 patients with advanced heart failure referred for heart transplant evaluation. All patients underwent right heart catheterization together with OCT evaluation of a subsegmentary pulmonary artery. RESULTS: OCT could be performed and properly analyzed in 90 patients. Median age was 57.50 [interquartile range, 48.75-63.25] years and 71 (78.88%) were men. The most frequent underlying heart condition was nonischemic dilated cardiomyopathy (33 patients [36.66%]). Vascular wall thickness significantly correlated with mean pulmonary artery pressure, pulmonary vascular resistance, and transpulmonary gradient (R coefficient=0.42, 0.27 and 0.32 respectively). Noninvasive estimation of pulmonary artery systolic pressure, acceleration time, and right ventricle-pulmonary artery coupling also correlated with wall thickness (R coefficient of 0.42, 0.27 and 0.49, respectively). Patients with a wall thickness over 0.25mm had significantly higher mean pulmonary pressures (37.00 vs 25.00mmHg; P=.004) and pulmonary vascular resistance (3.44 vs 2.08 WU; P=.017). CONCLUSIONS: Direct morphological assessment of pulmonary vascular remodeling with OCT is feasible and is significantly associated with classic hemodynamic parameters. This weak association suggests that structural remodeling does not fully explain pulmonary hypertension.

The original and two new derivative versions of the COMPERA 2.0 risk assessment model: useful tools for guiding balloon pulmonary angioplasty.

BACKGROUND: The COMPERA 2.0 4-stratum (4-S) risk score has been demonstrated superior over the 3-stratum (3-S) one in patients with pulmonary arterial hypertension and medically managed patients with chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to determine the prognostic value of the original 4-S and 3-S COMPERA 2.0 risk score and two new derivative versions in CTEPH patients who underwent balloon pulmonary angioplasty (BPA). METHODS: We retrospectively enrolled 175 BPA-treated patients with CTEPH. We assessed the risk stratification before and after each BPA session of CTEPH patients by the original 4-S and 3-S COMPERA 2.0 risk score (by rounding decimal to the nearest integer) and two new proposed derivative versions: the modified version (by rounding decimal to the next integer) and a hybrid version that fuses the original and modified versions. The primary endpoint was clinical worsening events. The secondary outcomes were achieving low-risk profile and mean pulmonary arterial pressure (mPAP) < 30 mmHg at follow-up. We used the Kaplan-Meier curve analysis to assess the survival differences between stratified patients. The comparative model's performance was evaluated in terms of discrimination by Harrell's C-index. RESULTS: All versions of COMPERA 2.0 4-S model outperformed the 3-S one in discriminating the differences in echocardiographic and hemodynamic parameters and clinical worsening-free survival rates. The original and hybrid 4-S model could independently predict the primary and secondary endpoints, and the hybrid version seemed to perform better. The first BPA session could significantly improve risk profiles, and these changes were associated with the likelihood of experiencing clinical worsening events, achieving a low-risk profile and mPAP < 30 mmHg at follow-up. The number of BPA sessions required to achieve low risk/mPAP < 30 mmHg increased as the baseline risk score escalated. CONCLUSIONS: The COMPERA 2.0 4-S model outperformed the 3-S one in BPA-treated patients with CTEPH. The 4-S model, especially its hybrid version, could be used to predict clinical outcome before the initiation of BPA and monitor treatment response.

The role of bedside functional echocardiography in the assessment and management of pulmonary hypertension.

Pulmonary hypertension is an emergency in neonatal intensive care units with high morbidity and mortality. Its timely assessment and management is crucial for intact survival. Over the last couple of decades, there have been significant advances in management and techniques, which have resulted in improved survival. The use of neonatologist-performed echocardiography (NPE) is now increasingly utilized on neonatal intensive care units to understand the pathophysiology of the disease and to direct the treatment to the underlying cause. Its use is now established not only in cases of congenital diaphragmatic hernia and in the newborn with refractory hypoxemia, but also in other conditions such as bronchopulmonary dysplasia and the premature infant with difficulty in oxygenation. The use of NPE, however, requires the availability of trained personnel, equipment, and a close working relationship with pediatric cardiology.

Assessment of pulmonary arterial stiffness in patients with systemic sclerosis without overt pulmonary hypertension.

Pulmonary hypertension (PH) is a pathophysiological disorder that may involve multiple clinical conditions and complicate most systemic diseases. Systemic sclerosis (SSc), represents the leading cause of connective tissue disease (CTD) associated with PAH. Although SSc is a rare disease, it is associated with higher morbidity and early mortality than other rheumatological diseases due to developing SSc-associated interstitial pulmonary disease (ILD) and/or pulmonary arterial hypertension (PAH). The impact of the early diagnosis on the prognosis is evident. In this context, in our study, we aimed to investigate the early changes in pulmonary vascular bed by measuring pulmonary arterial stiffness (PAS) in SSc patients without overt PAH. Sixty-two SSc patients and fifty-eight gender and age-matched, healthy subjects enrolled in this cross-sectional observational study. SSc patients were evaluated in terms of disease duration and severity. Modified rodnan skin score (mRSS) was calculated as disease severity index. Echocardiographic parameters were assessed and compared to the control group. Right ventricular (RV) diameters, systolic pulmonary artery pressure (sPAP), and right ventricle myocardial performance index (RV-MPI) were significantly higher in the SSc group compared to the control group (p < 0.05). Tricuspid annular plane systolic excursion (TAPSE) and right ventricular fractional area change (RVFAC) were significantly lower in the SSc group compared to the control group (p < 0.05). PAS value (25.5 ± 9.2 kHz/ms vs. 18.1 ± 7.4 kHz/ms, p < 0.001) was significantly higher in the SSc group than in the control group. A statistically significant positive correlation relationship was detected between the PAS value and CRP, ESR, disease duration, mRSS. According to these results, in SSc patients, PAS as an inexpensive and easily applicable echocardiographic method might serve as a marker of early detection of PAH.

Integrated Cardiopulmonary MRI Assessment of Pulmonary Hypertension.

Pulmonary hypertension (PH) is a heterogeneous condition that can affect the lung parenchyma, pulmonary vasculature, and cardiac chambers. Accurate diagnosis often requires multiple complex assessments of the cardiac and pulmonary systems. MRI is able to comprehensively assess cardiac structure and function, as well as lung parenchymal, pulmonary vascular, and functional lung changes. Therefore, MRI has the potential to provide an integrated functional and structural assessment of the cardiopulmonary system in a single exam. Cardiac MRI is used in the assessment of PH in most large PH centers, whereas lung MRI is an emerging technique in patients with PH. This article reviews the current literature on cardiopulmonary MRI in PH, including cine MRI, black-blood imaging, late gadolinium enhancement, T1 mapping, myocardial strain analysis, contrast-enhanced perfusion imaging and contrast-enhanced MR angiography, and hyperpolarized gas functional lung imaging. This article also highlights recent developments in this field and areas of interest for future research including cardiac MRI-based diagnostic models, machine learning in cardiac MRI, oxygen-enhanced 1 H imaging, contrast-free 1 H perfusion and ventilation imaging, contrast-free angiography and UTE imaging. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 3.

A Novel Non-Invasive Method for Estimating Elevated Pulmonary Vascular Resistance Based on Echocardiographic Assessment of Pulmonary Artery Wave Reflection.

BACKGROUND: Several non-invasive methods for pulmonary vascular resistance (PVR) measurement are proposed, but none are sufficiently accurate for use in clinical practice. This study proposes a new echocardiographic method of pulmonary artery wave reflection and investigates its efficacy in managing patients with pulmonary hypertension.Methods and Results:In total, 83 patients with left heart disease, pulmonary arterial hypertension, and chronic thromboembolic pulmonary hypertension (CTEPH), who underwent Doppler echocardiography and right heart catheterization, were included in the study. Pulmonary artery wave reflection was characterized by separating the pulmonary artery pressure waveform into forward and backward (Pb) waves, based on wave intensity. Pulmonary artery pressure waveforms were estimated from continuous Doppler tracings of tricuspid regurgitation velocity, and flow velocity was measured using pulsed Doppler of the right ventricular outflow tract. Pb-peak was compared with catheter hemodynamic indices, and with PVR by Abbas 2003, 2013 and Haddad in relation to increased catheter PVR. Catheter PVR and Pb were strongly correlated (r=0.77, P<0.001). The areas under the receiver operator characteristic curve for Pb-peak, PVR by Abbas 2003, 2013 and Haddad were 0.91, 0.72, 0.80, and 0.80, respectively, and were used to detect an increase in PVR (>3 Woods units). CONCLUSIONS: This study describes a novel, simple, and non-invasive echocardiography method to assess pulmonary wave reflected pressure to identify patients with pulmonary hypertension due to increased PVR.

Direct pixel to pixel principal strain mapping from tagging MRI using end to end deep convolutional neural network (DeepStrain).

Regional soft tissue mechanical strain offers crucial insights into tissue's mechanical function and vital indicators for different related disorders. Tagging magnetic resonance imaging (tMRI) has been the standard method for assessing the mechanical characteristics of organs such as the heart, the liver, and the brain. However, constructing accurate artifact-free pixelwise strain maps at the native resolution of the tagged images has for decades been a challenging unsolved task. In this work, we developed an end-to-end deep-learning framework for pixel-to-pixel mapping of the two-dimensional Eulerian principal strains [Formula: see text] and [Formula: see text] directly from 1-1 spatial modulation of magnetization (SPAMM) tMRI at native image resolution using convolutional neural network (CNN). Four different deep learning conditional generative adversarial network (cGAN) approaches were examined. Validations were performed using Monte Carlo computational model simulations, and in-vivo datasets, and compared to the harmonic phase (HARP) method, a conventional and validated method for tMRI analysis, with six different filter settings. Principal strain maps of Monte Carlo tMRI simulations with various anatomical, functional, and imaging parameters demonstrate artifact-free solid agreements with the corresponding ground-truth maps. Correlations with the ground-truth strain maps were R = 0.90 and 0.92 for the best-proposed cGAN approach compared to R = 0.12 and 0.73 for the best HARP method for [Formula: see text] and [Formula: see text], respectively. The proposed cGAN approach's error was substantially lower than the error in the best HARP method at all strain ranges. In-vivo results are presented for both healthy subjects and patients with cardiac conditions (Pulmonary Hypertension). Strain maps, obtained directly from their corresponding tagged MR images, depict for the first time anatomical, functional, and temporal details at pixelwise native high resolution with unprecedented clarity. This work demonstrates the feasibility of using the deep learning cGAN for direct myocardial and liver Eulerian strain mapping from tMRI at native image resolution with minimal artifacts.

k-t accelerated multi-VENC 4D flow MRI improves vortex assessment in pulmonary hypertension.

BACKGROUND: 4D flow imaging can be used to evaluate vortex formation in the pulmonary artery seen in patients with pulmonary hypertension. We evaluated if a k-t accelerated multi-VENC (velocity encoding) 4D flow acquisition improves image quality, inter-reader agreement and correlation with hemodynamic parameters. METHODS: A total of 14 patients with pulmonary hypertension (5 females, 9 males; mean age 61 ± 16 years) underwent 4D flow MRI (magnetic resonance imaging) and right heart catheterization. In addition to that, 13 healthy volunteers (2 females, 11 males, mean age 33 ± 12 years) also underwent 4D flow MRI. Multi- and single-VENC datasets were reconstructed and evaluated for vortex formation and vortex duration by two blinded readers and image quality was rated on a 5-point scale. RESULTS: Both readers rated image quality as significantly higher on multi-VENC datasets (3.96 ± 0.71 vs. 2.56 ± 0.93, p < 0.001; 4.70 ± 0.61 vs. 4.07 ± 0.92, p = 0.003). Inter-reader correlation for vortex duration quantification was higher on multi-VENC datasets compared to single-VENC datasets (r = 0.63 vs. r = 0.44). No significant correlation was found between vortex duration and mean pulmonary artery pressure in patients with PH. CONCLUSION: Multi-VENC 4D flow MRI significantly improves image quality and inter-reader agreement for the evaluation of vortex formation in the pulmonary artery.

Magnetic Resonance Imaging Assessment of Pulmonary Vascularity in Infants with Congenital Diaphragmatic Hernia: A Novel Tool for Direct Assessment of Severity of Pulmonary Hypertension and Hypoplasia.

OBJECTIVES: To assess the feasibility of magnetic resonance imaging (MRI) for postnatal assessment of pulmonary vascularity in infants with congenital diaphragmatic hernia (CDH). STUDY DESIGN: Infants with prenatally diagnosed CDH (n = 24) received postnatal pulmonary MRI. Infants with nonpulmonary birth defects served as controls (n = 5). Semiautomatic segmentation was performed to obtain total vascular volume using time of flight images to assess vascularity. RESULTS: Average vascular density (vascular volume/lung volume) in control infants was 0.23 ± 0.06 mm3/mm3 compared with 0.18 ± 0.06 mm3/mm3 in infants with CDH is (P = .09). When stratified further based on CDH severity, the difference between control infants and moderate CDH group was statistically significant. (0.23 mm3/mm3 vs 0.15 mm3/mm3, P = .01). Ipsilateral vascular density on MRI in infants with CDH significantly correlated with the prenatal pulmonary hypertensive index (P = .0004, Spearman R = +0.87) and with number of days on mechanical ventilation (P = .04, Spearman R = -0.44), total days on inhaled nitric oxide (P = .02, Spearman R = -0.47), use of epoprostenol for acute pulmonary hypertension (PH) (0.14 mm3/mm3 vs 0.20 mm3/mm3, P = .005), and use of sildenafil for chronic PH (0.15 mm3/mm3 vs 0.19 mm3/mm3, P = .03). CONCLUSIONS: Our results suggest that postnatal pulmonary vascularity assessed by MRI strongly correlates with prenatal and postnatal markers of PH severity and that pulmonary vascularity may serve as a direct measure of pulmonary vascular hypoplasia in infants with CDH.

Multimodal assessment of right ventricle overload-metabolic and clinical consequences in pulmonary arterial hypertension.

BACKGROUND: In pulmonary arterial hypertension (PAH) increased afterload leads to adaptive processes of the right ventricle (RV) that help to maintain arterio-ventricular coupling of RV and preserve cardiac output, but with time the adaptive mechanisms fail. In this study, we propose a multimodal approach which allows to estimate prognostic value of RV coupling parameters in PAH patients. METHODS: Twenty-seven stable PAH patients (49.5 ± 15.5 years) and 12 controls underwent cardiovascular magnetic resonance (CMR). CMR feature tracking analysis was performed for RV global longitudinal strain assessment (RV GLS). RV-arterial coupling was evaluated by combination of RV GLS and three proposed surrogates of RV afterload-pulmonary artery systolic pressure (PASP), pulmonary vascular resistance (PVR) and pulmonary artery compliance (PAC). 18-FDG positron emission tomography (PET) analysis was used to assess RV glucose uptake presented as SUVRV/LV. Follow-up time of this study was 25 months and the clinical end-point was defined as death or clinical deterioration. RESULTS: Coupling parameters (RV GLS/PASP, RV GLS/PVR and RV GLS*PAC) significantly correlated with RV function and standardized uptake value (SUVRV/LV). Patients who experienced a clinical end-point (n = 18) had a significantly worse coupling parameters at the baseline visit. RV GLS/PASP had the highest area under curve in predicting a clinical end-point and patients with a value higher than (-)0.29%/mmHg had significantly worse prognosis. It was also a statistically significant predictor of clinical end-point in multivariate analysis (adjusted R2 = 0.68; p < 0.001). CONCLUSIONS: Coupling parameters are linked with RV hemodynamics and glucose metabolism in PAH. Combining CMR and hemodynamic measurements offers more comprehensive assessment of RV function required for prognostication of PAH patients. TRIAL REGISTRATION: NCT03688698, 09/26/2018, retrospectively registered; Protocol ID: 2017/25/N/NZ5/02689.