scholarly journals Right Ventricular Function and Its Coupling With Pulmonary Circulation in Precapillary Pulmonary Hypertension: A Three-Dimensional Echocardiographic Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Yidan Li ◽  
Dichen Guo ◽  
Juanni Gong ◽  
Jianfeng Wang ◽  
Qiang Huang ◽  
...  

Objective: To assess right ventricular (RV) function and RV-pulmonary arterial (PA) coupling by three-dimensions echocardiography and investigate the ability of RV-PA coupling to predict adverse clinical outcomes in patients with precapillary pulmonary hypertension (PH).Methods: We retrospectively collected a longitudinal cohort of 203 consecutive precapillary PH patients. RV volume, RV ejection fraction (RVEF), and RV longitudinal strain (RVLS) were quantitatively determined offline by 3D echocardiography. RV-PA coupling parameters including the RVEF/PA systolic pressure (PASP) ratio, pulmonary arterial compliance (PAC), and total pulmonary resistance (TPR) were recorded.Results: Over a median follow-up period of 20.9 months (interquartile range, 0.1–67.4 months), 87 (42.9%) of 203 patients experienced adverse clinical outcomes. With increasing World Health Organization functional class (WHO-FC), significant trends were observed in increasing RV volume, decreasing RVEF, and worsening RVLS. RV arterial coupling (RVAC) and PAC were lower and TPR was higher for WHO-FC III+IV than WHO-FC I or II. The RVEF/PASP ratio showed a significant correlation with RVLS. RVAC had a stronger correlation with the RVEF/PASP ratio than other indices. Multivariate Cox proportional-hazard analysis identified a lower 3D RVEF and worse RVLS as strong predictors of adverse clinical events. RVAC, TPR, and PAC had varying degrees of predictive value, with optimal cutoff values of 0.74, 11.64, and 1.18, respectively.Conclusions: Precapillary-PH with RV-PA uncoupling as expressed by a RVEF/PASP ratio <0.44 was associated with adverse clinical outcomes. PAC decreased and TPR increased with increasing WHO-FC, with TPR showing better independent predictive value.

2019 ◽  
Vol 9 (2) ◽  
pp. 204589401984197 ◽  
Author(s):  
Priyanka T. Bhattacharya ◽  
Gregory S. Troutman ◽  
Frances Mao ◽  
Arieh L. Fox ◽  
Monique S. Tanna ◽  
...  

Pulmonary arterial compliance (PAC), invasively assessed by the ratio of stroke volume to pulmonary arterial (PA) pulse pressure, is a sensitive marker of right ventricular (RV)-PA coupling that differs across the spectrum of pulmonary hypertension (PH) and is predictive of outcomes. We assessed whether the echocardiographically derived ratio of RV outflow tract velocity time integral to PA systolic pressure (RVOT-VTI/PASP) (a) correlates with invasive PAC, (b) discriminates heart failure with preserved ejection-associated PH (HFpEF-PH) from pulmonary arterial hypertension (PAH), and (c) is associated with functional capacity. We performed a retrospective cohort study of patients with PAH (n = 70) and HFpEF-PH (n = 86), which was further dichotomized by diastolic pressure gradient (DPG) into isolated post-capillary PH (DPG < 7 mmHg; Ipc-PH, n = 54), and combined post- and pre-capillary PH (DPG ≥ 7 mm Hg; Cpc-PH, n = 32). Of the 156 patients, 146 had measurable RVOT-VTI or PASP and were included in further analysis. RVOT-VTI/PASP correlated with invasive PAC overall (ρ = 0.61, P < 0.001) and for the PAH (ρ = 0.38, P = 0.002) and HFpEF-PH (ρ = 0.63, P < 0.001) groups individually. RVOT-VTI/PASP differed significantly across the PH spectrum (PAH: 0.13 [0.010–0.25] vs. Cpc-PH: 0.20 [0.12–0.25] vs. Ipc-PH: 0.35 [0.22–0.44]; P < 0.001), distinguished HFpEF-PH from PAH (AUC = 0.72, 95% CI = 0.63–0.81) and Cpc-PH from Ipc-PH (AUC = 0.78, 95% CI = 0.68–0.88), and remained independently predictive of 6-min walk distance after multivariate analysis (standardized β-coefficient = 27.7, 95% CI = 9.2–46.3; P = 0.004). Echocardiographic RVOT-VTI/PASP is a novel non-invasive metric of PAC that differs across the spectrum of PH. It distinguishes the degree of pre-capillary disease within HFpEF-PH and is predictive of functional capacity.


2015 ◽  
Vol 309 (10) ◽  
pp. L1164-L1173 ◽  
Author(s):  
Michiel Alexander de Raaf ◽  
Yvet Kroeze ◽  
Anthonieke Middelman ◽  
Frances S. de Man ◽  
Helma de Jong ◽  
...  

Increased serotonin serum levels have been proposed to play a key role in pulmonary arterial hypertension (PAH) by regulating vessel tone and vascular smooth muscle cell proliferation. An intact serotonin system, which critically depends on a normal function of the serotonin transporter (SERT), is required for the development of experimental pulmonary hypertension in rodents exposed to hypoxia or monocrotaline. While these animal models resemble human PAH only with respect to vascular media remodeling, we hypothesized that SERT is likewise required for the presence of lumen-obliterating intima remodeling, a hallmark of human PAH reproduced in the Sugen hypoxia (SuHx) rat model of severe angioproliferative pulmonary hypertension. Therefore, SERT wild-type (WT) and knockout (KO) rats were exposed to the SuHx protocol. SERT KO rats, while completely lacking SERT, were hemodynamically indistinguishable from WT rats. After exposure to SuHx, similar degrees of severe angioproliferative pulmonary hypertension and right ventricular hypertrophy developed in WT and KO rats (right ventricular systolic pressure 60 vs. 55 mmHg, intima thickness 38 vs. 30%, respectively). In conclusion, despite its implicated importance in PAH, SERT does not play an essential role in the pathogenesis of severe angioobliterative pulmonary hypertension in rats exposed to SuHx.


2017 ◽  
Vol 8 (1) ◽  
pp. 204589321775312 ◽  
Author(s):  
Christoph B. Wiedenroth ◽  
Karen M. Olsson ◽  
Stefan Guth ◽  
Andreas Breithecker ◽  
Moritz Haas ◽  
...  

Symptomatic patients with residual pulmonary perfusion defects or vascular lesions but no pulmonary hypertension at rest are diagnosed with chronic thromboembolic disease (CTED). Balloon pulmonary angioplasty (BPA) is an emerging treatment for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH), but data regarding the safety and efficacy of BPA in patients with CTED are lacking. We report a prospective series of ten consecutive patients with CTED who underwent 35 BPA interventions (median of four per patient) at two German institutions. All patients underwent a comprehensive diagnostic workup at baseline and 24 weeks after their last intervention. BPA was safe, with one pulmonary vascular injury and subsequent self-limiting pulmonary bleeding as the only complication (2.9% of the interventions, 10% of the patients). After the procedures, World Health Organization functional class, 6-min walking distance, pulmonary vascular resistance, and pulmonary arterial compliance improved, and NT-proBNP concentrations declined in 9/10 patients. BPA may be a new treatment option for carefully selected patients with CTED. A larger, prospective, international registry is required to confirm these results.


2019 ◽  
Vol 9 (3) ◽  
pp. 204589401987715 ◽  
Author(s):  
Alexandra Arvanitaki ◽  
Maria Boutsikou ◽  
Anastasia Anthi ◽  
Sotiria Apostolopoulou ◽  
Aikaterini Avgeropoulou ◽  
...  

Pulmonary arterial hypertension (PAH) is a heterogenous clinical entity with poor prognosis, despite recent major pharmacological advances. To increase awareness about the pathophysiology, epidemiology, and management of the disease, large national registries are required. The Hellenic pulmOnary hyPertension rEgistry (HOPE) was launched in early 2015 and enrolls patients from all pulmonary hypertension subgroups in Greece. Baseline epidemiologic, diagnostic, and initial treatment data of consecutive patients with PAH are presented in this article. In total, 231 patients with PAH were enrolled from January 2015 until April 2018. At baseline, about half of patients with PAH were in World Health Organization functional class II. The majority of patients with PAH (56.7%) were at intermediate 1-year mortality risk, while more than one-third were low-risk patients, according to an abbreviated risk stratification score. Half of patients with PAH were on monotherapy, 38.9% received combination therapy, while prostanoids were used only in 12.1% of patients. In conclusion, baseline data of the Greek PAH population share common characteristics, but also have some differences with other registries, the most prominent being a better functional capacity. This may reflect earlier diagnosis of PAH that in conjunction with the increased proportion of patients with atypical PAH could partially explain the preference for monotherapy and the limited use of prostanoids in Greece. Nevertheless, early, advanced specific therapy is strongly recommended.


1991 ◽  
Vol 70 (2) ◽  
pp. 859-868 ◽  
Author(s):  
B. D. Zuckerman ◽  
E. C. Orton ◽  
K. R. Stenmark ◽  
J. A. Trapp ◽  
J. R. Murphy ◽  
...  

We compared main pulmonary arterial elasticity and global pulmonary arterial compliance in control and high-altitude (HA) calves to determine whether 1) changes in pulmonary arterial elasticity are contributing to an increase in the oscillatory load of the right ventricle in this model of pulmonary hypertension and 2) measured changes in stiffness of the HA calves' arterial wall are the result of both an increase in pressure and an alteration of the material properties of the HA calves' arterial wall. Newborn calves were placed at 4,300 m simulated altitude for 14 days, and control calves were kept at 1,500 m. The HA calves were then reacclimatized to 1,500 m for 24 h so that baseline pressures of the two groups were similar. Open-chest main pulmonary arterial and right ventricular micromanometric pressures, ultrasonic main pulmonary arterial diameter, and green dye flow were measured under baseline conditions and then under moderate and severely hypoxic conditions to make measurements at both baseline and increased pulmonary pressures. At elevated pressures, the pressure-diameter relationship was noted to be nonlinear, and a characteristic late systolic peaking of the right ventricular pressure waveform was seen. The Peterson pressure-strain modulus, pulse wave velocity, characteristic impedance, and global compliance (3 element windkessel) were calculated. The calculated variables were all shown to be pressure dependent, and no intrinsic differences in stiffness were seen between the control and HA animals when mean pressure was taken into account. Pulmonary arterial histology demonstrated, however, a characteristic increase in wall thickness in the HA animals. Thus, in this model of pulmonary hypertension, major changes in elasticity and pulsatile load are primarily due to an increase in pulmonary pressure. The structural changes present in the HA calves' arterial wall did not separately produce any measurable changes in arterial distensibility or the oscillatory load.


2016 ◽  
Vol 310 (4) ◽  
pp. L299-L310 ◽  
Author(s):  
Xiaochen Li ◽  
Yuanzhou He ◽  
Yongjian Xu ◽  
Xiaomin Huang ◽  
Jin Liu ◽  
...  

Hypoxic pulmonary hypertension (HPH) is characterized by active vasoconstriction and profound vascular remodeling. KLF5, a zinc-finger transcription factor, is involved in the excessive proliferation and apoptotic resistance phenotype associated with monocrotaline-induced pulmonary hypertension. However, the molecular mechanisms of KLF5-mediated pathogenesis of HPH are largely undefined. Adult male Sprague-Dawley rats were exposed to normoxia or hypoxia (10% O2) for 4 wk. Hypoxic rats developed pulmonary arterial remodeling and right ventricular hypertrophy with significantly increased right ventricular systolic pressure. The levels of KLF5 and hypoxia-inducible factor-1α (HIF-1α) were upregulated in distal pulmonary arterial smooth muscle from hypoxic rats. The knockdown of KLF5 via short-hairpin RNA attenuated chronic hypoxia-induced hemodynamic and histological changes in rats. The silencing of either KLF5 or HIF-1α prevented hypoxia-induced (5%) proliferation and migration and promoted apoptosis in human pulmonary artery smooth muscle cells. KLF5 was immunoprecipitated with HIF-1α under hypoxia and acted as an upstream regulator of HIF-1α. The cell cycle regulators cyclin B1 and cyclin D1 and apoptosis-related proteins including bax, bcl-2, survivin, caspase-3, and caspase-9, were involved in the regulation of KLF5/HIF-1α-mediated cell survival. This study demonstrated that KLF5 plays a crucial role in hypoxia-induced vascular remodeling in an HIF-1α-dependent manner and provided a better understanding of the pathogenesis of HPH.


2021 ◽  
pp. 1-15
Author(s):  
Lars K. Markvardsen ◽  
Lene D. Sønderskov ◽  
Christine Wandall-Frostholm ◽  
Estéfano Pinilla ◽  
Judit Prat-Duran ◽  
...  

<b><i>Introduction:</i></b> Pulmonary hypertension is characterized by vasoconstriction and remodeling of pulmonary arteries, leading to right ventricular hypertrophy and failure. We have previously found upregulation of transglutaminase 2 (TG2) in the right ventricle of chronic hypoxic rats. The hypothesis of the present study was that treatment with the transglutaminase inhibitor, cystamine, would inhibit the development of pulmonary arterial remodeling, pulmonary hypertension, and right ventricular hypertrophy. <b><i>Methods:</i></b> Effect of cystamine on transamidase activity was investigated in tissue homogenates. Wistar rats were exposed to chronic hypoxia and treated with vehicle, cystamine (40 mg/kg/day in mini-osmotic pumps), sildenafil (25 mg/kg/day), or the combination for 2 weeks. <b><i>Results:</i></b> Cystamine concentration-dependently inhibited TG2 transamidase activity in liver and lung homogenates. In contrast to cystamine, sildenafil reduced right ventricular systolic pressure and hypertrophy and decreased pulmonary vascular resistance and muscularization in chronic hypoxic rats. Fibrosis in the lung tissue decreased in chronic hypoxic rats treated with cystamine. TG2 expression was similar in the right ventricle and lung tissue of drug and vehicle-treated hypoxic rats. <b><i>Discussion/Conclusions:</i></b> Cystamine inhibited TG2 transamidase activity, but cystamine failed to prevent pulmonary hypertension, right ventricular hypertrophy, and pulmonary arterial muscularization in the chronic hypoxic rat.


2020 ◽  
Vol 10 (4) ◽  
pp. 204589402093984
Author(s):  
Ailing Li ◽  
Zhongkai Zhu ◽  
Yangke He ◽  
Qian Dong ◽  
Dianyong Tang ◽  
...  

Pulmonary arterial hypertension is a progressive, malignant heart disease, characterized by pulmonary arteriole remodeling and increased pulmonary vascular resistance, which eventually leads to right heart failure. This study sought to evaluate the effects of a novel long-acting phospdiesterase-5 inhibitor, namely DDCI-01, as an early intervention for monocrotaline-induced pulmonary hypertensive rats. To establish this model, 50 mg/kg of monocrotaline was intraperitoneally injected into rats. At Day 7 after monocrotaline injection, two doses of DDCI-01 (3 or 9 mg/kg/day) or tadalafil (at 3 or 9 mg/kg/day) were intragastrically administered. The rats were anesthetized with pentobarbital for hemodynamic and echocardiographic measurements, at Day 21 after monocrotaline injection. Compared to the monocrotaline group, DDCI-01 at 3 and 9 mg/kg/day (P) reduced the mean pulmonary arterial pressure (mPAP), right ventricular systolic pressure, right ventricular transverse diameter, pulmonary arterial medial wall thickness (WT%), and right ventricle hypertrophy. However, no significant difference in the indices mentioned as above was found between DDCI-01 (3 mg/kg/day) and tadalafil (3 mg/kg/day). In addition, DDCI-01 at 9 mg/kg/day resulted in lower mPAP and WT%, as well as higher cyclic guanosine monophosphate levels in the lung and plasma compared with the same dose of tadalafil (9 mg/kg/day) (all P < 0.05). These findings suggested that DDCI-01 improved monocrotaline-induced pulmonary hypertension in rats, and a dose of DDCI-01 of 9 mg/kg/day might be more effective than the same dose of tadalafil in monocrotaline-induced pulmonary hypertension in rats.


2015 ◽  
Vol 12 (3) ◽  
pp. 50-55
Author(s):  
Z Kh Dadacheva ◽  
A A Belevskaya ◽  
M A Saidova ◽  
N M Danilov ◽  
T V Martyniuk ◽  
...  

Over the last decade, the interest in the treatment of idiopathic pulmonary hypertension (IPAH) has greatly increased because of the development and implementation of innovative therapeutic approaches. One of the modern drug groups for the treatment of pulmonary arterial hypertension are phosphodiesterase type 5 inhibitors (PDE5), which can cause pulmonary vasodilation via a NO-dependent mechanism.The aim of the research was to study the efficacy and safety of sildenafil treatment in patients with IPAH received 16-week course and to study sildenafil impact on clinical, hemodynamic and functional status.Material and methods: 20 patients with IPAH (mean age 40.9±11.5 years) functional class (FC) II-IV (WHO), who were receiving standard therapy (anticoagulants, diuretics, glycosides, calcium antagonists), were prescribed sildenafil 20 mg three times a day for 16 weeks. Initially, and after 16 weeks of treatment we studied FC, and the results of the six-minute walk test (6MWT), transthoracic echocardiography (ECHO), right heart catheterization (RHC) and laboratory tests to determine the safety of the therapy were carried out, as well.Results: the group of patients had 6MWT distance of 344±116 m at the beginning of the study. For about 90% of the patients suffered from dizziness, 75% - from the pain in the heart, 65% of the patients had edema and 35% - hepatomegaly. The patients suffered from severe pulmonary hypertension according to the functional and hemodynamic status. The estimated pulmonary artery systolic pressure (PASP) according to ECHO results was 89.6±22 mm Hg. According to the data from RHC we noted the elevation of mean pulmonary arterial pressure (mPAP) to 56.3±19 mm Hg, of pulmonary vascular resistance (PVR) to 1218±709 dyne/sec x per x cm-5 and the decrease in cardiac output (CO) - 3.4±0.8 l/min/m2.There were slight increasing in 6MWT distance (+23 m, p>0.05) and a statistically significant improvement in clinical status in comparison with the initial data: dizziness - 71%, heart pain - 38%, edema and hepatomegaly were observed in 15% and 14% (p


2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Daniele Guarino ◽  
Massimiliano Palazzini ◽  
Francesco Saia ◽  
Fabio Dardi ◽  
Nevio Taglieri ◽  
...  

Abstract Aims Balloon pulmonary angioplasty (BPA) has recently been developed as a treatment strategy for chronic thromboembolic pulmonary hypertension (CTEPH) but efficacy and technical safety have to be established. We examine the effects of BPA on patients with inoperable disease or residual pulmonary hypertension (PH) after pulmonary endarterectomy (PEA). Methods and results From 2015 to 2020 we enrolled symptomatic inoperable CTEPH patients and patients with residual PH after PEA. At baseline and 3 months after last BPA session patients underwent clinical evaluation, 6-min walking distance (6MWD), and right heart catheterization. Friedman test with Bonferroni post-hoc pairwise analysis was used. Fifty patients [male 42%, median age 68 (51–74) years, 42 inoperable, and 8 with residual PH after PEA] were treated for a total of 156 sessions (median 2 sessions/patient); during each session we treated 2.3 (2.2–2.7) vessels. Results are shown in the Table. Forty-nine patients were treated with medical therapy before BPA (19 with combination therapy). Five pulmonary artery dissection and two haemoptysis with clinical impairment were documented during the procedures; 37 patients had lung injury (radiographic opacity with/without haemoptysis and/or hypoxaemia), none had renal dysfunction, 7 patients had access site complications. Seven patients died during follow-up (none within 30 days from the procedure) because of sepsis (1), heart failure (1), cancer (2), arrhythmic storm (2), and sudden death in patients with severe coronary atherosclerosis (1). Conclusions BPA is a safe and effective treatment able to improve symptoms and haemodynamic profile. 45 Table 16MWD, six minute walking distanceCI, cardiac index; mPAP, mean pulmonary arterial pressure; PAC, pulmonary arterial compliance; PVR, pulmonary vascular resistance; RAP, right atrial pressure; SvO2, mixed venous oxygen saturation; WHO-FC, World Health Organization functional class.


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