Noninvasive diagnostic modalities and prediction models for detecting pulmonary hypertension associated with interstitial lung disease: a narrative review.

Pulmonary hypertension (PH) is highly prevalent in patients with interstitial lung disease (ILD) and is associated with increased morbidity and mortality. Widely available noninvasive screening tools are warranted to identify patients at risk for PH, especially severe PH, that could be managed at expert centres. This review summarises current evidence on noninvasive diagnostic modalities and prediction models for the timely detection of PH in patients with ILD. It critically evaluates these approaches and discusses future perspectives in the field. A comprehensive literature search was carried out in PubMed and Scopus, identifying 39 articles that fulfilled inclusion criteria. There is currently no single noninvasive test capable of accurately detecting and diagnosing PH in ILD patients. Estimated right ventricular pressure (RVSP) on Doppler echocardiography remains the single most predictive factor of PH, with other indirect echocardiographic markers increasing its diagnostic accuracy. However, RVSP can be difficult to estimate in patients due to suboptimal views from extensive lung disease. The majority of existing composite scores, including variables obtained from chest computed tomography, pulmonary function tests and cardiopulmonary exercise tests, were derived from retrospective studies, whilst lacking validation in external cohorts. Only two available scores, one based on a stepwise echocardiographic approach and the other on functional parameters, predicted the presence of PH with sufficient accuracy and used a validation cohort. Although several methodological limitations prohibit their generalisability, their use may help physicians to detect PH earlier. Further research on the potential of artificial intelligence may guide a more tailored approach, for timely PH diagnosis.

Current Overview of the Biology and Pharmacology in Sugen/Hypoxia-Induced Pulmonary Hypertension in Rats.

The Sugen 5416/hypoxia (Su/Hx) rat model of pulmonary arterial hypertension (PAH) demonstrates most of the distinguishing features of PAH in humans, including increased wall thickness and obstruction of the small pulmonary arteries along with plexiform lesion formation. Recently, significant advancement has been made describing the epidemiology, genomics, biochemistry, physiology, and pharmacology in Su/Hx challenge in rats. For example, there are differences in the overall reactivity to Su/Hx challenge in different rat strains and only female rats respond to estrogen treatments. These conditions are also encountered in human subjects with PAH. Also, there is a good translation in both the biochemical and metabolic pathways in the pulmonary vasculature and right heart between Su/Hx rats and humans, particularly during the transition from the adaptive to the nonadaptive phase of right heart failure. Noninvasive techniques such as echocardiography and magnetic resonance imaging have recently been used to evaluate the progression of the pulmonary vascular and cardiac hemodynamics, which are important parameters to monitor the efficacy of drug treatment over time. From a pharmacological perspective, most of the compounds approved clinically for the treatment of PAH are efficacious in Su/Hx rats. Several compounds that show efficacy in Su/Hx rats have advanced into phase II/phase III studies in humans with positive results. Results from these drug trials, if successful, will provide additional treatment options for patients with PAH and will also further validate the excellent translation that currently exists between Su/Hx rats and the human PAH condition.

Right ventricular-pulmonary artery uncoupling in patients with atrial fibrillation on peritoneal dialysis.

BACKGROUND: Tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) as a noninvasively measured index of right ventricular-pulmonary artery uncoupling is associated with poor outcomes in heart failure patients. However, the relationship by which the TAPSE/PASP is linked to atrial fibrillation (AF) in peritoneal dialysis (PD) patients is not clear. We aimed to investigate the relationship between the TAPSE/PASP and AF in PD patients. METHODS: This study was divided into two parts. First, we included 329 PD patients. All the subjects provided detailed a medical history, laboratory analysis and transthoracic echocardiography on admission. We evaluated the differences in the TASPE/PASP ratios between the AF and non-AF groups. Second, a total of 121 patients were followed up to compare mortality between the AF and non-AF groups. RESULTS: Age, BNP, RDW, LA, and septal E/e' were significantly higher, and TAPSE/PASP was significantly lower in patients with AF than in those without AF (p < 0.05). Moreover, the TAPSE/PASP was more pronounced in persistent AF patients. PD patients with AF had a greater risk of mortality (7.2%) than did those without AF (3.8%) after an average follow-up of 12 months. Kaplan-Meier analysis revealed that patients with TAPSE/PASP ratios ≤ 0.715 had a greater risk of mortality than did those with TAPSE/PASP ratios > 0.715. CONCLUSIONS: The results suggested that the TAPSE/PASP was lower in AF patients than in non-AF patients. The TAPSE/PASP may be a useful factor for predicting mortality in AF patients with PD, but large-scale prospective studies are needed for verification.

Quercetin regulates pulmonary vascular remodeling in pulmonary hypertension by downregulating TGF-ß1-Smad2/3 pathway.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a worldwide challenging disease characterized by progressive elevation of pulmonary artery pressure. The proliferation, migration and phenotypic transformation of pulmonary smooth muscle cells are the key steps of pulmonary vascular remodeling. Quercetin (3,3', 4', 5, 6-pentahydroxyflavone, Que) is a natural flavonol compound that has antioxidant, anti-inflammatory, anti-tumor and other biological activities. Studies have shown that Que has therapeutic effects on PAH. However, the effect of quercetin on pulmonary vascular remodeling in PAH and its mechanism remain unclear. METHODS AND RESULTS: In vivo, PAH rats were constructed by intraperitoneal injection of monocrotaline (MCT) at 60 mg/kg. Human pulmonary artery smooth muscle cells (HPASMCs) were treated with platelet-derived growth factor BB (PDGF-BB) 20 ng/mL to construct PAH cell model in vitro. The results showed that in vivo studies, MCT could induce right ventricular wall hyperplasia, narrow the small and medium pulmonary artery cavity, up-regulate the expression of proliferating and migration-related proteins proliferating cell nuclear antigen (PCNA) and osteopontin (OPN), and down-regulate the expression of alpha-smooth muscle actin (α-SMA). Que reversed the MCT-induced results. This process works by down-regulating the transforming growth factor-ß1 (TGF-ß1)/ Smad2/3 signaling pathway. In vitro studies, Que had the same effect on PDGF-BB-induced proliferation and migration cell models. CONCLUSIONS: Que inhibits the proliferation, migration and phenotypic transformation of HPASMCs by down-regulating TGF-ß1/Smad2/Smad3 pathway, thereby reducing right ventricular hyperplasia (RVH) and pulmonary vascular remodeling, providing potential pharmacological and molecular explanations for the treatment of PAH.

Prognostic Value of Pulmonary Artery Systolic Pressure in Severe Rheumatic Mitral Stenosis.

BACKGROUND: Current guidelines recommend intervention for asymptomatic rheumatic mitral stenosis (MS) with mitral valve area ≤1.5 cm2 based on indicators including pulmonary arterial systolic pressure (PASP) >50 mm Hg and new-onset atrial fibrillation; however, evidence supporting this is lacking. METHODS: This single-center retrospective study included patients with rheumatic MS between 2006 and 2022. Pulmonary hypertension was evaluated by using echocardiography to estimate PASP. Primary outcomes were major adverse cardiovascular events (MACE), including all-cause mortality, hospitalization for heart failure, and arterial thromboembolic events for up to 5 years. RESULTS: Overall, 287 patients with severe rheumatic MS were enrolled (mean age, 62.5±11.3 years; 74.6% women). During a median follow-up of 2.52 years, MACE occurred in 99 patients. There were no differences in echocardiographic parameters, such as the mean mitral valve pressure gradient, mitral valve area, and proportion of mitral valve area <1.0 cm2, between patients who developed primary outcomes and those who did not. Survival analysis showed a worse prognosis in patients with estimated PASP (ePASP) >50 mm Hg than in those with ePASP ≤50 mm Hg (log-rank P<0.001); however, atrial fibrillation was not a significant prognostic indicator. As a continuous variable, ePASP (mm Hg) was a significant predictor of MACE (adjusted hazard ratio, 1.027 [95% CI, 1.011-1.042]; P<0.001). Receiver operating characteristic analysis revealed an optimal ePASP threshold of >45 mm Hg, which was an independent predictor of MACE in patients with severe rheumatic MS (adjusted hazard ratio, 2.127 [95% CI, 1.424-3.177]; P<0.001). Competing risk analysis considering mitral valve intervention as a competing risk showed similar results. CONCLUSIONS: Our study demonstrated the prognostic significance of ePASP, rather than atrial fibrillation, in relation to MACE among patients with severe rheumatic MS. Additionally, we proposed a lower ePASP threshold (>45 mm Hg) as a predictor of an unfavorable prognosis.

Chronic diesel exhaust exposure induced pulmonary vascular remodeling a potential trajectory for traffic related pulmonary hypertension.

BACKGROUND: As one of the most common traffic-related pollutants, diesel exhaust (DE) confers high risk for cardiovascular and respiratory diseases. However, its impact on pulmonary vessels is still unclear. METHODS: To explore the effects of DE exposure on pulmonary vascular remodeling, our study analyzed the number and volume of small pulmonary vessels in the diesel engine testers (the DET group) from Luoyang Diesel Engine Factory and the controls (the non-DET group) from the local water company, using spirometry and carbon content in airway macrophage (CCAM) in sputum. And then we constructed a rat model of chronic DE exposure, in which 12 rats were divided into the DE group (6 rats with 16-week DE exposure) and the control group (6 rats with 16-week clean air exposure). During right heart catheterization, right ventricular systolic pressure (RVSP) was assessed by manometry. Macrophage migration inhibitory factor (MIF) in lung tissues and bronchoalveolar lavage fluid (BALF) were measured by qRT-PCR and ELISA, respectively. Histopathological analysis for cardiovascular remodeling was also performed. RESULTS: In DET cohort, the number and volume of small pulmonary vessels in CT were positively correlated with CCAM in sputum (P<0.05). Rat model revealed that chronic DE-exposed rats had elevated RVSP, along with increased wall thickness of pulmonary small vessels and right the ventricle. What's more, the MIF levels in BALF and lung tissues were higher in DE-exposed rats than the controls. CONCLUSION: Apart from airway remodeling, DE also induces pulmonary vascular remodeling, which will lead to cardiopulmonary dysfunction.

G6pdN126D Variant Increases the Risk of Developing VEGFR (Vascular Endothelial Growth Factor Receptor) Blocker-Induced Pulmonary Vascular Disease.

BACKGROUND: G6PD (glucose-6-phosphate-dehydrogenase) is a key enzyme in the glycolytic pathway and has been implicated in the pathogenesis of cancer and pulmonary hypertension-associated vascular remodeling. Here, we investigated the role of an X-linked G6pd mutation (N126D polymorphism), which is known to increase the risk of cardiovascular disease in individuals from sub-Saharan Africa and many others with African ancestry, in the pathogenesis of pulmonary hypertension induced by a vascular endothelial cell growth factor receptor blocker used for treating cancer. METHODS AND RESULTS: CRISPR-Cas9 genome editing was used to generate the G6pd variant (N126D; G6pdN126D) in rats. A single dose of the vascular endothelial cell growth factor receptor blocker sugen-5416 (SU; 20 mg/kg in DMSO), which is currently in a Phase 2/3 clinical trial for cancer treatment, was subcutaneously injected into G6pdN126D rats and their wild-type littermates. After 8 weeks of normoxic conditions, right ventricular pressure and hypertrophy, pulmonary artery remodeling, the metabolic profile, and cytokine expression were assessed. Right ventricular pressure and pulmonary arterial wall thickness were increased in G6PDN126D+SU/normoxic rats. Simultaneously, levels of oxidized glutathione, inositol triphosphate, and intracellular Ca2+ were increased in the lungs of G6PDN126D+SU/normoxic rats, whereas nitric oxide was decreased. Also increased in G6PDN126D+SU/normoxic rats were pulmonary levels of plasminogen activator inhibitor-1, thrombin-antithrombin complex, and expression of proinflammatory cytokines CCL3 (chemokine [C-C motif] ligand), CCL5, and CCL7. CONCLUSIONS: Our results suggest G6PDN126D increases inositol triphosphate-Ca2+ signaling, inflammation, thrombosis, and hypertrophic pulmonary artery remodeling in SU-treated rats. This suggests an increased risk of vascular endothelial cell growth factor receptor blocker-induced pulmonary hypertension in those carrying this G6PD variant.

Performance study of dual heart assisted control system based on SL-SMC physiological combination controller.

The main challenges of Biventricular Assist Devices (BiVAD) as a treatment modality for patients with Bicardiac heart failure heart failure are the balance of systemic blood flow during changes in physiological activity and the prevention of ventricular suction. In this study, a model of the Biventricular Circulatory System (BCS) was constructed and a physiological combination controller based on Starling-Like controller and Sliding Mode Controller (SMC) was proposed. The effects of the physiological controller on the hemodynamics of the BCS were investigated by simulating two sets of physiological state change experiments: elevated pulmonary artery resistance and resting-exercise, with constant speed (CS) control and combined Starling-like and PI control (SL-PI) as controllers. Simulation and experimental results showed that the Starling-like and Sliding Mode Control (SL-SMC) physiological combination controller was effective in preventing the occurrence of ventricular suction, providing higher cardiac output, maintain balance of systemic blood flow, and have higher response speed and robustness in the face of physiological state changes.

Rationale and design of the randomized COmparison of Methods for Pulmonary blood flow Augmentation: Shunt versus Stent (COMPASS) trial: A Pediatric Heart Network study.

Neonates with congenital heart disease (CHD) and ductal-dependent pulmonary blood flow (DD-PBF) require early intervention. Historically, this intervention was most often a surgical systemic-to-pulmonary shunt (SPS; e.g., Blalock-Thomas-Taussig shunt). However, over the past two decades an alternative to SPS has emerged in the form of transcatheter ductal artery stenting (DAS). While many reports have indicated safety and durability of the DAS approach, few studies compare outcomes between DAS and SPS. The reports that do exist are comprised primarily of small-cohort single-center reviews. Two multicenter retrospective studies suggest that DAS is associated with similar or superior survival compared to SPS. These studies offer the best evidence to-date, and yet both have important limitations. The authors describe herein the rationale and design of the COMPASS (COmparison of Methods for Pulmonary blood flow Augmentation: Shunt vs. Stent) Trial (NCT05268094, IDE G210212). The COMPASS Trial aims to randomize 236 neonates with DD-PBF to either DAS or SPS across approximately 27 pediatric centers in North America. The goal of this trial is to compare important clinical outcomes between DAS and SPS over the first year of life in a cohort of neonates balanced by randomization to assess whether one method of palliation demonstrates therapeutic superiority.

Carotid Baroreceptor Stimulation Ameliorates Pulmonary Arterial Remodeling in Rats With Hypoxia-Induced Pulmonary Hypertension.

BACKGROUND: Sympathetic hyperactivity plays an important role in the initiation and maintenance of pulmonary hypertension. Carotid baroreceptor stimulation (CBS) is an effective autonomic neuromodulation therapy. We aim to investigate the effects of CBS on hypoxia-induced pulmonary hypertension and its underlying mechanisms. METHODS AND RESULTS: Rats were randomly assigned into 4 groups, including a Control-sham group (n=7), a Control-CBS group (n=7), a Hypoxia-sham group (n=10) and a Hypoxia-CBS group (n=10). Echocardiography, ECG, and hemodynamics examination were performed. Samples of blood, lung tissue, pulmonary arteries, and right ventricle were collected for the further analysis. In the in vivo study, CBS reduced wall thickness and muscularization degree in pulmonary arterioles, thereby improving pulmonary hemodynamics. Right ventricle hypertrophy, fibrosis and dysfunction were all improved. CBS rebalanced autonomic tone and reduced the density of sympathetic nerves around pulmonary artery trunks and bifurcations. RNA-seq analysis identified BDNF and periostin (POSTN) as key genes involved in hypoxia-induced pulmonary hypertension, and CBS downregulated the mRNA expression of BDNF and POSTN in rat pulmonary arteries. In the in vitro study, norepinephrine was found to promote pulmonary artery smooth muscle cell proliferation while upregulating BDNF and POSTN expression. The proliferative effect was alleviated by silence BDNF or POSTN. CONCLUSIONS: Our results showed that CBS could rebalance autonomic tone, inhibit pulmonary arterial remodeling, and improve pulmonary hemodynamics and right ventricle function, thus delaying hypoxia-induced pulmonary hypertension progression. There may be a reciprocal interaction between POSTN and BDNF that is responsible for the underlying mechanism.

Unraveling the Mfn2-Warburg effect nexus: a therapeutic strategy to combat pulmonary arterial hypertension arising from catch-up growth after IUGR.

BACKGROUND: The interplay between intrauterine and early postnatal environments has been associated with an increased risk of cardiovascular diseases in adulthood, including pulmonary arterial hypertension (PAH). While emerging evidence highlights the crucial role of mitochondrial pathology in PAH, the specific mechanisms driving fetal-originated PAH remain elusive. METHODS AND RESULTS: To elucidate the role of mitochondrial dynamics in the pathogenesis of fetal-originated PAH, we established a rat model of postnatal catch-up growth following intrauterine growth restriction (IUGR) to induce pulmonary arterial hypertension (PAH). RNA-seq analysis of pulmonary artery samples from the rats revealed dysregulated mitochondrial metabolic genes and pathways associated with increased pulmonary arterial pressure and pulmonary arterial remodeling in the RC group (postnatal catch-up growth following IUGR). In vitro experiments using pulmonary arterial smooth muscle cells (PASMCs) from the RC group demonstrated elevated proliferation, migration, and impaired mitochondrial functions. Notably, reduced expression of Mitofusion 2 (Mfn2), a mitochondrial outer membrane protein involved in mitochondrial fusion, was observed in the RC group. Reconstitution of Mfn2 resulted in enhanced mitochondrial fusion and improved mitochondrial functions in PASMCs of RC group, effectively reversing the Warburg effect. Importantly, Mfn2 reconstitution alleviated the PAH phenotype in the RC group rats. CONCLUSIONS: Imbalanced mitochondrial dynamics, characterized by reduced Mfn2 expression, plays a critical role in the development of fetal-originated PAH following postnatal catch-up growth after IUGR. Mfn2 emerges as a promising therapeutic strategy for managing IUGR-catch-up growth induced PAH.

The effects of percutaneous branch pulmonary artery interventions in biventricular congenital heart disease: study protocol for a randomized controlled Dutch multicenter interventional trial.

BACKGROUND: Branch pulmonary artery (PA) stenosis is one of the most common indications for percutaneous interventions in patients with transposition of the great arteries (TGA), tetralogy of Fallot (ToF), and truncus arteriosus (TA). However, the effects of percutaneous branch PA interventions on exercise capacity remains largely unknown. In addition, there is no consensus about the optimal timing of the intervention for asymptomatic patients according to international guidelines. This trial aims to identify the effects of percutaneous interventions for branch PA stenosis on exercise capacity in patients with TGA, ToF, and TA. In addition, it aims to assess the effects on RV function and to define early markers for RV adaptation and RV dysfunction to improve timing of these interventions. METHODS: This is a randomized multicenter interventional trial. TGA, ToF, and TA patients ≥ 8 years with a class IIa indication for percutaneous branch PA intervention according to international guidelines are eligible to participate. Patients will be randomized into the intervention group or the control group (conservative management for 6 months). All patients will undergo transthoracic echocardiography, cardiac magnetic resonance (CMR) imaging, and cardiopulmonary exercise testing at baseline, 6 months, and 2-4 years follow-up. Quality of life (QoL) questionnaires will be obtained at baseline, 2 weeks post intervention or a similar range for the control group, and 6 months follow-up. The primary outcome is exercise capacity expressed as maximum oxygen uptake (peak VO2 as percentage of predicted). A total of 56 patients (intervention group n = 28, control group n = 28) is required to demonstrate a 14% increase in maximum oxygen uptake (peak VO2 as percentage of predicted) in the interventional group compared to the control group (power 80%, overall type 1 error controlled at 5%). Secondary outcomes include various parameters for RV systolic function, RV functionality, RV remodeling, procedural success, complications, lung perfusion, and QoL. DISCUSSION: This trial will investigate the effects of percutaneous branch PA interventions on exercise capacity in patients with TGA, ToF, and TA and will identify early markers for RV adaptation and RV dysfunction to improve timing of the interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT05809310. Registered on March 15, 2023.

Pulmonary Vein in a Pinch.

The pulmonary veins normally drain into the left atrium, with the superior pulmonary veins typically situated anterior and inferior to the right pulmonary arteries. However, anomalies can happen. We encountered an exceedingly rare pulmonary vascular anomaly for a patient presenting with atypical chest pain, where the right superior pulmonary vein aberrantly ran posterior to the right pulmonary artery (RPA) and became compressed between the RPA and the right main bronchus. Coronary computed tomography angiography identified this specific pulmonary vein anomaly but revealed unremarkable coronary arteries.

Rat Model of Right-Sided Cardiac Remodeling and Arrhythmia using Pulmonary Artery Banding.

Clinical conditions, including chronic obstructive pulmonary disease or pulmonary arterial hypertension (PAH), can lead to chronic right ventricle pressure overload and progressive right heart failure (RHF). RHF can be identified by right-sided cardiac hypertrophy and dilation associated with abnormal myocardial function affecting the RV and the right atrium (RA). We recently demonstrated that severe RHF is accompanied by an increased risk of atrial inflammation, atrial fibrosis, and atrial fibrillation (AF), the most common type of cardiac arrhythmia (CA). Recent studies have shown that RV and RA inflammation plays an important role in the arrhythmogenesis of CA, including AF. However, the impact of inflammation in the development of CA and AF in RHF is poorly described. Experimental models of RHF are required to better understand the association between right-sided myocardial inflammation and CA. The rat model of monocrotaline (MCT)-induced pulmonary hypertension (PH) is well-established to provoke RHF. However, MCT triggers severe pneumo-toxicity and pulmonary inflammation. Hence, MCT-induced RHF does not help to distinguish whether the subsequent myocardial inflammation originates from the RHF per se or circulating inflammatory signals secreted by the injured lung. In this article, a mechanical method involving pulmonary artery trunk banding (PAB) was used to provoke right-sided cardiac arrhythmogenesis. The PAB consists of performing a permanent suture of the pulmonary artery trunk for 3 weeks. Such an approach generates increased right-sided pressure overload. At D21 post-PAB, the suture results in hypertrophied, dilated, and inflamed RV and RA. The PAB-induced RHF is also accompanied by vulnerability to ventricular and atrial arrhythmias, including AF.

Sex Dimorphism in Pulmonary Arterial Hypertension Associated With Autoimmune Diseases.

Pulmonary hypertension is a rare, incurable, and progressive disease. Although there is increasing evidence that immune disorders, particularly those associated with connective tissue diseases, are a strong predisposing factor in the development of pulmonary arterial hypertension (PAH), there is currently a lack of knowledge about the detailed molecular mechanisms responsible for this phenomenon. Exploring this topic is crucial because patients with an immune disorder combined with PAH have a worse prognosis and higher mortality compared with patients with other PAH subtypes. Moreover, data recorded worldwide show that the prevalence of PAH in women is 2× to even 4× higher than in men, and the ratio of PAH associated with autoimmune diseases is even higher (9:1). Sexual dimorphism in the pathogenesis of cardiovascular disease was explained for many years by the action of female sex hormones. However, there are increasing reports of interactions between sex hormones and sex chromosomes, and differences in the pathogenesis of cardiovascular disease may be controlled not only by sex hormones but also by sex chromosome pathways that are not dependent on the gonads. This review discusses the role of estrogen and genetic factors including the role of genes located on the X chromosome, as well as the potential protective role of the Y chromosome in sexual dimorphism, which is prominent in the occurrence of PAH associated with autoimmune diseases. Moreover, an overview of animal models that could potentially play a role in further investigating the aforementioned link was also reviewed.

Evaluation of right ventricular function in patients with Behcet's disease by four-dimensional echocardiography.

AIM: Behcet's disease (BD) is a systemic disorder characterized by vasculitis, resulting in thickened vascular walls that reduce elasticity and impair function. BD can involve the cardiovascular system in three ways: cardiac, arterial, and venous. In this study, our objective was to evaluate the efficacy of pulmonary arterial stiffness (PAS) and pulmonary pulse transit time (PPTT) measures in demonstrating right ventricular functions in asymptomatic BD patients. We aimed to objectively evaluate right ventricular function in patients with BD using four-dimensional echocardiography (4DE). METHOD: This study included 40 patients diagnosed with BD and 40 healthy subjects. Demographic, clinical, laboratory, and echocardiographic parameters were compared. In addition to standard transthoracic echocardiographic evaluation, right ventricle quantification (RVQ) by using the 4DE and 2D-speckle tracking echocardiography were performed. RESULTS: The sPAP, 4D RVQ, and right ventricular strain values exhibited significant differences between the BD and control groups. Right ventricular end-diastolic diameter (RVDD), right ventricular end-systolic diameter (RVSD), right atrium (RA) area, right ventricular myocardial performance index (RVMPI), and PAS were increased in BD patients compared to the control group. Right ventricular ejection fraction (RVEF), right ventricular fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), Tricuspid S', and PPTT were decreased in BD patients compared to control subjects. PPTT correlated with right ventricular free wall strain (RV-FWS) and PAS. In a multivariate linear regression analysis, PAS and RVFAC were found to be independent predictors of RVFWS. In addition, RVFAC and TAPSE are independent predictors for PPTT. CONCLUSION: Patients with BD may have elevated pulmonary arterial stiffness (PAS) in correlation with decreased PPTT. To ascertain the prognosis for these individuals, right ventricular (RV) functions must be evaluated. Measurements of RVFAC and RVEF via 4DE and deformation imaging techniques may be more useful in identifying subclinical impairment of RV. Individuals with BD, PAS, and PPTT may suggest a link between early pulmonary vascular remodeling and RV subclinical impairment.

Effectiveness of Vericiguat on right ventricle to pulmonary artery uncoupling associated with heart failure with reduced ejection fraction.

BACKGROUNDS: A soluble guanylyl cyclase stimulator vericiguat has been shown to reduce cardiovascular mortality or hospitalization for heart failure in patients with worsening heart failure in the VICTORIA study. However, little is known about the effects of vericiguat on biventricular structure and function. METHODS AND RESULTS: A retrospective analysis of 63 consecutive patients with heart failure with reduced ejection fraction (HFrEF) who were treated with vericiguat was performed. Clinical data and echocardiographic parameters were compared between baseline and follow-up after the initiation of vericiguat. The median follow-up duration was 266 days. Treatment with vericiguat significantly reduced the plasma BNP levels (log-transformed) compared to baseline (2.46 ± 0.51 vs. 2.14 ± 0.58, p < 0.0001). Left ventricular end-diastolic volume index and left ventricular end-systolic volume index were significantly reduced (LVEDVI, 113.5 ± 46.3 vs. 103.6 ± 51.0, p = 0.0056; LVESVI, 82.0 ± 41.9 vs. 72.8 ± 44.7, p = 0.0077; respectively). The tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) ratio, an indicator of right ventricle-pulmonary artery (RV-PA) coupling, increased significantly after the treatment (0.56 ± 0.29 vs. 0.92 ± 1.09, p < 0.0001). Univariate and multivariate analyses showed that the treatment effects of vericiguat on BNP levels, LV reverse remodeling, and RV-PA coupling were not correlated with the achievement of the quadruple therapy with beta-blockers, renin-angiotensin system inhibitors, mineralocorticoid inhibitors, and sodium-glucose cotransporter-2 inhibitors, nor with worsening heart failure (WHF). CONCLUSION: Treatment with vericiguat improved adverse LV remodeling and RV-PA uncoupling in HFrEF patients. These effects were independent of WHF and achieving the quadruple therapy. Patients with HFrEF may benefit from early initiation of vericiguat to prevent biventricular adverse remodeling.

Animal models of pulmonary arterial hypertension associated with atrial septal defect.

Pulmonary arterial hypertension (PAH) is a well-known complication of congenital heart disease (CHD). The lack of a satisfactory animal model for PAH associated with CHD (PAH-CHD) has limited progress in understanding the pathogenesis of PAH and the development of therapeutic agents. The development of a rat model for PAH associated with atrial septal defect (ASD) was achieved through atrial septal puncture and thermal ablation. Two and 4 weeks after modeling, hematoxylin and eosin staining showed that the vascular thickness, vascular thickness index, vascular area, and vascular area index in pulmonary arteries with an outer diameter of 50-300 µm in the PAH-ASD 2 and 4 weeks group were higher than those in the sham group (all P < 0.05). Alpha-smooth muscle actin (ɑ-SMA) staining showed that the medial thickness, medial thickness index, medial area, and medial area index in pulmonary arteries with an outer diameter of 50-300 µm at 2 and 4 weeks after modeling were significantly higher than those in the sham group (all P < 0.05). Additionally, mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) in the PAH-ASD 2 and 4 weeks groups were significantly higher than those in the sham group (both P < 0.05). Elastin van Gieson staining showed that the vascular obstruction score in the PAH-ASD 2 and 4 weeks group was significantly higher than that in the sham group (both P < 0.05). The PAH-ASD rats were successfully generated. These findings suggest that our model would be useful for further research into the pathogenesis, prevention, and treatment of PAH-ASD.