Effect Of Pulmonary Hypertension Research Articles

Obesity and hypoxia have differential effects on myocardial innervation in the right ventricle of the male mouse heart.

Obesity, along with hypoxia, is known to be a risk factor for pulmonary hypertension (PH), which can lead to right ventricular hypertrophy and eventually heart failure. Both obesity and PH influence the autonomic nervous system (ANS), potentially aggravating changes in the right ventricle (RV). This study investigates the combined effects of obesity and hypoxia on the autonomic innervation of the RV in a mouse model. Male C57BL/6N mice were subjected to a control diet (CD) or a high-fat diet (HFD) for 30 weeks, with subsets of the mice exposed to chronic normobaric hypoxia (13% O2) during the final 3 weeks. Light and electron microscopic stereology was used to quantify various parameters of nerve fibres innervating the RV myocardium. HFD-induced obesity significantly increased the total length of nerve fibres and axons in the RV under normoxic conditions, indicating hyperinnervation. Quantitatively, the length density of nerve fibres per unit volume of RV (unit: x10-3 µm-2) was similar in CD (0.158 ± 0.04), CD-Hyp (0.176 ± 0.06) and HFD-Hyp (0.147 ± 0.05). In contrast, in HFD the length density of nerve fibres showed higher values 0.206 ± 0.054. The total length of nerve fibres increased by 67% from 2.61 m ± 0.77 m in CD to 4.37 m ± 1.51 m in HFD. The total length of axons increased by 80% from 8.87 m ± 2.75 m to 15.95 m ± 4.62 m. However, when obesity was combined with hypoxia, the total axon length was significantly reduced by 27% in HFD-Hyp compared with HFD. In addition, the mean number of axon profiles per nerve fibre profile decreased from 3.44 ± 0.68 in HFD to 2.95 ± 0.43 in HFD-Hyp. Interestingly, chronic hypoxia alone did not significantly alter RV innervation but led to RV hypertrophy, independent of the diet. The attenuation of obesity-induced hyperinnervation by hypoxia suggests a complex and potentially antagonistic interaction between these conditions. In conclusion, obesity induced by a HFD caused hyperinnervation of the RV, whereas chronic hypoxia alone did not significantly alter RV innervation. Surprisingly, chronic hypoxia attenuated the obesity-induced changes in RV innervation. These findings indicate that the effects of obesity and hypoxia-induced PH on RV innervation are distinct and potentially antagonistic.

Exploring the patient perspective in pulmonary hypertension.

The global impacts of pulmonary hypertension (PH) were formally recognised in 1973 at the 1st World Health Organization meeting dedicated to primary pulmonary hypertension, held in Geneva. Investigations into disease pathogenesis and classification led to the development of numerous therapies over the ensuing decades. While the impacts of the disease have been lessened due to treatments, the symptoms and adverse effects of PH and its therapies on patients' wellbeing and mental health remain significant. As such, there is a critical need to enhance understanding of the challenges patients face on a global scale with respect to care access, multidimensional patient support and advocacy. In addition, thoughtful analysis of the potential benefits and utilisation of mechanisms for the incorporation of patient-reported outcomes into diagnosis and treatment plans is needed. A summary of these areas is included here. We present a report of global surveys of patient and provider experiences and challenges regarding care access and discuss possible solutions. Also addressed is the current state of PH patient associations around the world. Potential ways to enhance patient associations and enable them to provide the utmost support are discussed. A summary of relevant patient-reported outcome measures to assess health-related quality of life in PH is presented, with suggestions regarding incorporation of these tools in patient care and research. Finally, information on how current global threats such as pandemics, climate change and armed conflict may impact PH patients is offered, along with insights as to how they may be mitigated with advanced contingency planning.

Pulmonary hypertension: An unexplored risk factor for stroke in patients with atrial fibrillation

BackgroundAtrial fibrillation (Afib) is one of the most common and significant risk factors for stroke, with the CHADsVAsc score used as the tool for stroke risk assessment. Pulmonary hypertension (PH) has not been studied as an independent risk factor for stroke in individuals with Afib. MethodsIn this retrospective case-control study, National Inpatient Sample Database was used to sample individuals with atrial fibrillation, and baseline demographics and comorbidities were collected using ICD-10 codes. Patients with missing data, age under 18, history of thromboembolic diseases, or stroke were excluded. Greedy propensity matching using R was performed to match patients with and without PH on age, race, gender, and 19 other comorbidities, including anticoagulation use. Binary logistic regression was performed after matching to assess whether PH was an independent risk factor for stroke. A p-value of <0.05 was considered statistically significant. ResultsOf the 2,421,545 patients included in the study, 158,545 (6.5%) had PH. PH patients were more likely to be elderly, females, and smokers. Comorbidities were more common in the PH group. Patients with PH were more likely to have an ischemic stroke (3.6% vs. 2.9%, p<0.001), hemorrhagic stroke (2.2% vs. 0.7%, p<0.001), and transient ischemic attack (TIA) (2.3% vs. 0.7%, p<0.001). After matching, the presence of PH was associated with increased ischemic stroke (OR: 1.2 [1.1-1.2]; p<0.001), hemorrhagic stroke (OR: 2.4 [2.1-2.6]; p<0.001) and TIA (OR: 2.2 [2.0-2.4]; p<0.001). PH patients also had increased length of stay (β = 0.8; p<0.001) mortality (OR: 1.1 [1.0-1.2]; p<0.001). ConclusionApart from demonstrating the deleterious effect of PH on mortality and length of hospital stay, this study is the first to report on such a large scale that PH independently increases the incidence of all types of strokes in patients with Afib.

Natural Targeting Potent ROS-Eliminating Tungsten-Based Polyoxometalate Nanodots for Efficient Treatment of Pulmonary Hypertension.

Pulmonary hypertension (PH) is a disease of pulmonary artery stenosis and blockage caused by abnormal pulmonary artery smooth muscle cells (PASMCs), with high morbidity and mortality. High levels of reactive oxygen species (ROS) in pulmonary arteries play a crucial role in inducing phenotypic switch and abnormal proliferation of PASMCs. However, antioxidants are rarely approved for the treatment of PH because of a lack of targeting and low bioavailability. In this study, the presence of an enhanced permeability and retention effect (EPR)-like effect in the pulmonary arteries of PH is revealed by tissue transmission electron microscopy (TEM). Subsequently, for the first time, tungsten-based polyoxometalate nanodots (WNDs) are developed with potent elimination of multiple ROS for efficient treatment of PH thanks to the high proportion of reduced W5+ . WNDs are effectively enriched in the pulmonary artery by intravenous injection because of the EPR-like effect of PH, and significantly prevent the abnormal proliferation of PASMCs, greatly improve the remodeling of pulmonary arteries, and ultimately improve right heart function. In conclusion, this work provides a novel and effective solution to the dilemma of targeting ROS for the treatment of PH.

Functional and molecular determinants of right ventricular response to severe pulmonary hypertension in a large animal model.

Right ventricular (RV) failure is the major determinant of outcome in pulmonary hypertension (PH). Calves exposed to 2-wk hypoxia develop severe PH and unlike rodents, hypoxia-induced PH in this species can lead to right heart failure. We, therefore, sought to examine the molecular and structural changes in the RV in calves with hypoxia-induced PH, hypothesizing that we could identify mechanisms underlying compensated physiological function in the face of developing severe PH. Calves were exposed to 14 days of environmental hypoxia (equivalent to 4,570 m/15,000 ft elevation, n = 29) or ambient normoxia (1,525 m/5,000 ft, n = 25). Cardiopulmonary function was evaluated by right heart catheterization and pressure volume loops. Molecular and cellular determinants of RV remodeling were analyzed by cDNA microarrays, RealTime PCR, proteomics, and immunochemistry. Hypoxic exposure induced robust PH, with increased RV contractile performance and preserved cardiac output, yet evidence of dysregulated RV-pulmonary artery mechanical coupling as seen in advanced disease. Analysis of gene expression revealed cellular processes associated with structural remodeling, cell signaling, and survival. We further identified specific clusters of gene expression associated with 1) hypertrophic gene expression and prosurvival mechanotransduction through YAP-TAZ signaling, 2) extracellular matrix (ECM) remodeling, 3) inflammatory cell activation, and 4) angiogenesis. A potential transcriptomic signature of cardiac fibroblasts in RV remodeling was detected, enriched in functions related to cell movement, tissue differentiation, and angiogenesis. Proteomic and immunohistochemical analysis confirmed RV myocyte hypertrophy, together with localization of ECM remodeling, inflammatory cell activation, and endothelial cell proliferation within the RV interstitium. In conclusion, hypoxia and hemodynamic load initiate coordinated processes of protective and compensatory RV remodeling to withstand the progression of PH.NEW & NOTEWORTHY Using a large animal model and employing a comprehensive approach integrating hemodynamic, transcriptomic, proteomic, and immunohistochemical analyses, we examined the early (2 wk) effects of severe PH on the RV. We observed that RV remodeling during PH progression represents a continuum of transcriptionally driven processes whereby cardiac myocytes, fibroblasts, endothelial cells, and proremodeling macrophages act to coordinately maintain physiological homeostasis and protect myocyte survival during chronic, severe, and progressive pressure overload.

Impact of Pulmonary Hypertension on Renal Functions in Obstructive Sleep Apnea Syndrome

Pulmonary hypertension (PH) is common in obstructive sleep apnea syndrome (OSAS). This study aimed to evaluate the effect of PH on kidney functions in patients with OSAS. The data of patients who were diagnosed as having OSAS after referral to the sleep center in the Gaziantep University Medical Faculty between January 2005 and June 2017 were evaluated. The estimated glomerular filtration rate was calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Renal functions of the subjects who had data after 5 years were included for long-term analysis. A total of 2152 patients with OSAS (n = 1540), PH (n = 49), OSAS and PH coexistence (n = 359), and the control group (n = 204) were included in the study. Pulmonary arterial pressure (PAP) was 44.51 ± 23.73 in the PH group; it was 37.1 ± 13.14 in the group with OSAS + PH (P = 0.001) Urea and uric acid were found to be higher in the association of OSAS + PH. CKD-EPI was lower in the presence of PH or OSAS + PH than in the presence of OSAS. PH was present in 16.06% of males and 25.10% of females (P = 0.000), and PAP was detected as 35.80 ± 13.23 and 40.96 ± 16.65, respectively (P = 0.001). PH was present in 15.99% of males and 25.84% of females with OSAS (P = 0.000). The PAP of males with OSAS was 36.03 ± 13.46, and the PAP of females was 38.68 ± 12.55 (P = 0062). Urea, creatinine, and uric acid were higher and CKD-EPI was lower in male subjects in the presence of OSAS and PH, whereas the same scenario also was present in the presence of PH alone in female subjects. Long-term comparisons (n = 343) revealed significant decreases in the CKD-EPI in those with OSAS and OSAS + PH and these decrease were more pronounced in the presence of OSAS and PH. The regression analysis revealed that female patients had lower CKD-EPI in the presence of PH, although the presence of PH had no effect on CKD-EPI in males. PH is a risk factor for the deterioration of renal function in OSAS and more prominent in the long term.

Pulmonary hypertension is associated with poor cardiovascular and hematologic outcomes in patients with myeloproliferative neoplasms and cardiovascular disease.

Cardiovascular events and hematologic progression to myelofibrosis or leukemia are leading causes of morbidity and mortality among patients with myeloproliferative neoplasms (MPN). Pulmonary hypertension (PH) is also associated with MPN and cardiovascular disease (CVD), though its prognostic significance in MPN is not well characterized. Our primary objective was to investigate the effect of PH, defined as right-ventricular systolic pressure (RVSP) ≥ 50mmHg on echocardiogram or mean pulmonary artery pressure (mPAP) ≥ 20 on right heart catheterization, on cardiovascular and all-cause mortality and hematologic progression in patients with MPN and CVD (atrial fibrillation, heart failure hospitalization, and myocardial infarction after MPN diagnosis). Of the 197 patients included (86 ET, 80 PV, 31 PMF), 92 (47%) had PH and 98 (50%) were male. All-cause mortality (58 vs 37%, p = 0.004), cardiovascular death (35 vs 9%, p < 0.0001), and hematologic progression (23 vs 11%, p = 0.037) occurred more frequently in patients with PH. Multivariable competing-risk and proportional hazards regression showed that PH was associated with increased risk of all-cause death (adjusted hazard ratio [HR], 1.80, 95% CI 1.10-2.93), CV death (adjusted subdistribution HR 3.71, 95% CI 1.58-8.73), and hematologic progression (adjusted subdistribution HR 1.99, 95% CI 1.21-3.27).

Impact of borderline pulmonary hypertension due to left heart failure on mortality in a multicenter registry study: A 3-year survivorship analysis.

BackgroundPatients with left heart failure (LHF) are often associated with the development of pulmonary hypertension (PH) which leads to an increased risk of death. Recently, the diagnostic standard for PH has changed from mean pulmonary arterial pressure (mPAP) ≥25 mmHg to >20 mmHg. Nonetheless, the effect of borderline PH (mPAP: 21–24 mmHg) on the prognosis of LHF patients is unclear. This study aimed to investigate the relationship between borderline PH and 3-year clinical outcomes in LHF patients.MethodsA retrospective analysis of a prospective cohort study was done for LHF patients who underwent right heart catheterization (RHC) between January 2013 and November 2016. The primary outcome was all-cause mortality; the secondary outcome was rehospitalization.ResultsAmong 344 patients, 62.5% were identified with a proportion of PH (mPAP ≥ 25), 10.8% with borderline PH (21–24), and 26.7% with non-PH (≤20), respectively. Multivariable Cox analysis revealed that borderline PH patients had a higher adjusted mortality risk (HR = 3.822; 95% CI: 1.043–13.999; p = 0.043) than non-PH patients. When mPAP was treated as a continuous variable, the hazard ratio for death increased progressively with increasing mPAP starting at 20 mmHg (HR = 1.006; 95% CI: 1.001–1.012). There was no statistically significant difference in adjusted rehospitalization between borderline PH and non-PH patients (HR = 1.599; 95% CI: 0.833–3.067; p = 0.158).ConclusionsBorderline PH is independently related to increased 3-year mortality in LHF patients. Future research is needed to evaluate whether more close monitoring, and managing with an intensifier improves clinical outcomes in borderline PH caused by LHF.Clinical trials registrationwww.clinicaltrials.gov NCT02164526.

TPN171H alleviates pulmonary hypertension via inhibiting inflammation in hypoxia and monocrotaline-induced rats

Pulmonary hypertension (PH) is a progressive and life-threatening disease with poor prognosis despite many advances in medical therapy over the past 20 years. Novel therapies which target on the underlying pathology of PH are still urgent to be met. TPN171H is a recently found new compound that exhibits potent pharmacological effects in PH via inhibiting phosphodiesterase type 5 (PDE-5). However, as one icariin derivative, the anti-inflammatory effects of TPN171H for treating PH are not clear. The present study was designed to investigate the therapeutical effect of TPN171H against inflammation in PH and reveal the underlying mechanism. Hypoxia and monocrotaline (MCT)-induced PH rat models were established, which were treated by oral administration of TPN171H (5, 25 mg/kg/d) or sildenafil (25 mg/kg/d). The right ventricle systolic pressure (RVSP), right ventricle hypertrophy index (RVHI) and vascular remodeling were measured. The results suggested that TPN171H significantly reduced RVSP and RVHI, and reversed pulmonary vascular remodeling in rats with both models. Furthermore, in in vivo and in vitro research, our data suggested that TPN171H remarkably suppressed cathepsin B-mediated NLRP3 inflammasome activation, which may contribute to its therapeutical function for PH.

Monocrotaline‐induced Pulmonary Hypertension Impairs Diaphragm Vasomotor Function

INTRODUCTIONPulmonary hypertension (PH) is a chronic and progressive disease characterized by high arterial blood pressure and compensatory vascular remodeling in the pulmonary circulation. Mounting evidence suggests that the effects of PH extend beyond the pulmonary circulation. In humans and animals, PH induces diaphragm contractile dysfunction and diaphragm muscle atrophy. While the mechanistic bases for the PH‐induced diaphragm dysfunction is relatively unknown, alterations in the vasomotor control of the diaphragm resistance vasculature (i.e. arterioles) may play a key role. Therefore, we tested the hypothesis that PH increases the vasoconstrictor responsiveness and impairs the vasorelaxation of diaphragm arterioles.METHODSAdult female Sprague‐Dawley rats (n=8) were divided into healthy control (HC; n=2), ovariectomized (OVX; n=3), and PH + OVX (n=3). PH + OVX animals were given a single intraperitoneal injection of monocrotaline (MCT; 50mg/kg) to induce PH. Disease progression was then monitored via echocardiography. Once animals developed PH (~3 weeks post injection), the diaphragm was removed and first‐order arterioles (1A) from the medial costal diaphragm were isolated, cannulated, and pressurized at 90 cmH2O. After a 60 min equilibration period and spontaneous tone development, vasoconstrictor responses to potassium chloride (KCl) (10‐100 mM) and endothelium‐dependent and ‐independent vasorelaxation responses to cumulative doses of acetylcholine (ACh) and sodium nitroprusside (SNP) (10‐9 to 10‐4 M) were determined.RESULTSSpontaneous tone (%) development was not different across all three groups (HC: 36 ± 9%; OVX: 33 ± 9%; PH + OVX: 39 ± 2%; P&gt;0.05). Compared to control vessels, maximal percent vasoconstriction with KCl was decreased with OVX (67 ± 2 versus 50 ± 1%; P&lt;0.05). Maximal vasoconstriction (%) was reduced with PH + OVX (36 ± 4%) compared to vessels from both healthy control and OVX groups (P&lt;0.05). Ovariectomy had no effect on endothelium‐dependent vasodilation responses to ACh versus intact control animals (P&gt;0.05). The maximal ACh‐mediated vasodilation with PH + OVX (29 ± 9%) was decreased versus both healthy (45 ± 6%; P&lt;0.05) and OVX animals (41 ± 4%; P&lt;0.05). Across all three groups, there were no differences in percent relaxation with SNP (P&gt;0.05).CONCLUSIONThese findings suggest that estrogen plays a role in the maintenance of K+ channel activity and/or the contribution of K+ channels to diaphragm vasomotor tone, and that PH further disrupts K+ channel function in diaphragm arterioles. In addition, the absence of estrogen in OVX animals had no effect on endothelial function whereas PH + OVX impaired endothelium‐dependent vasorelaxation of diaphragm resistance vessels. These findings suggest that PH, at least in the rodent model utilized herein, elicits endothelial dysfunction in the diaphragm vasculature and provide a potential mechanism for the impaired diaphragm contractile dysfunction in PH patients.

The Effect of Borderline Pulmonary Hypertension on Survival in Chronic Lung Disease

Background: The impact of the new “borderline” hemodynamic class for pulmonary hypertension (PH) (mean pulmonary artery pressure [mPAP], 21–24 mm Hg and pulmonary vascular resistance, [PVR], ≥3 wood units, [WU]) in chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) is unclear. Objectives: The aim of this study was to assess the effect of borderline PH (BLPH) on survival in COPD and ILD patients. Method: Survival was analyzed from retrospective data from 317 patients in 12 centers (Italy, Spain, UK) comparing four hemodynamic groups: the absence of PH (NoPH; mPAP <21 mm Hg or 21–24 mm Hg and PVR <3 WU), BLPH (mPAP 21–24 mm Hg and PVR ≥3 WU), mild-moderate PH (MPH; mPAP 25–35 mm Hg and cardiac index [CI] ≥2 L/min/m²), and severe PH (SPH; mPAP ≥35 mm Hg or mPAP ≥25 mm Hg and CI <2 L/min/m²). Results: BLPH affected 14% of patients; hemodynamic severity did not predict survival when COPD and ILD patients were analyzed together. However, survival in the ILD cohort for any PH level was worse than in NoPH (3-year survival: NoPH 58%, BLPH 32%, MPH 28%, SPH 33%, p = 0.002). In the COPD cohort, only SPH had reduced survival compared to the other groups (3-year survival: NoPH 82%, BLPH 86%, MPH 87%, SPH 57%, p = 0.005). The mortality risk correlated significantly with mPAP in ILD (hazard ratio [HR]: 2.776, 95% CI: 2.057–3.748, p < 0.001) and notably less in COPD patients (HR: 1.015, 95% CI: 1.003–1.027, p = 0.0146). Conclusions: In ILD, any level of PH portends worse survival, while in COPD, only SPH presents a worse outcome.

Role of Pulmonary Hypertension in Acute Exacerbation of Chronic Obstructive Pulmonary Disease; Outcomes and Healthcare Utilization

<h3>Purpose</h3> Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD). Mortality in COPD and PH has significantly improved due to advances made in the field, however, the effect of PH during acute exacerbation of COPD (AECOPD) remains unknown. We aim to analyze the outcomes, 30-day readmission rates, and healthcare resource utilization associated with PH in patients with AECOPD. <h3>Methods</h3> We used the 2016 and 2017 National Readmission Database with an inclusion criterion of AECOPD as a primary and PH as a secondary diagnosis using ICD 10-CM codes. Exclusion criteria were age under 18 years, non-elective admissions to better assess readmission rates and discharges in December. The primary outcome was in-hospital mortality during the index admission. Secondary outcomes were 30-day readmission rate, Length of stay (LOS), resource utilization, and instrument utilization including intubation, prolonged invasive mechanical ventilation >96hr (PIMV), tracheostomy, chest tube placement, and bronchoscopy during the index admission. <h3>Results</h3> A total of 627,848 patients with AECOPD were included in the study, and 68,429 (10.90 %) patients had a diagnosis of PH. PH was more common among females (61.14%) with a mean age of 71 ±11.66, Medicare recipients (79.5%), higher Charlson Comorbidity Index, and treatment in an urban teaching hospital. PH was associated with greater in-hospital mortality [Adjusted odds ratio (aOR): 1.89, p<0.001], higher 30-day readmission (aOR: 1.24, p<0.001), higher LOS [adjusted mean difference (aMD): 1.09, p<0.001], higher cost (aMD: $2785, p<0.01), and higher instrument utilization including intubation (aOR: 1.99, p<0.001), PIMV (aOR: 2.12, p<0.001), tracheostomy (aOR: 2.15, p<0.001), bronchoscopy (aOR:1.46, p=0.007) and chest tube placement (aOR: 1.39 p<0.004). <h3>Conclusion</h3> Our study indicates that PH is associated with greater in-hospital mortality, LOS, and 30-day readmission among patients with AECOPD. It is also associated with increased procedure utilization and higher healthcare resource utilization leading to increased hospital expenses. These factors lead to a detrimental effect on a patient's well-being and impact their quality of life. Prompt diagnosis and appropriate treatment of PH in patients with COPD may improve outcomes in these patients.

Targeting Myadm to Intervene Pulmonary Hypertension on Rats Before Pregnancy Alleviates the Effect on Their Offspring's Cardiac-Cerebral Systems.

Pregnancy with pulmonary hypertension (PH) seriously threatens the life and safety of mothers and infants. Here, the long-term effect of maternal PH on the postpartum growth of rat offspring was focused for the first time, as well as explored the role of Myadm in PH rats before pregnancy based upon the previous findings. Patients with PH are prone to hypoxemia, leading to insufficient placental structure and function, which affects the organ function of fetuses, followed by evidence that differently expressed genes (DEGs) existed in the heart of maternal PH newborn rats and enriched in pathways related to cardiac and nerve development on human infants with similar birth outcome: low birth weight (LBW). LBW was one of the possible birth outcomes of pregnancy with PH, especially severe PH, accompanied by evidence that offspring derived from mothers with PH presented lower birth weights and slower growth rates than those derived from normal control mothers in a rat model. Besides, maternal PH rat offspring showed cardiac remodeling and a significant elevation of the expression levels of hypoxia- and inflammation-related markers in the cerebral cortex at both 10 and 14 weeks of age, respectively. What is more, the previous studies found that the overexpression of Myadm could result in the remodeling of the pulmonary artery. And targeting Myadm to intervene PH before pregnancy could alleviate sustained low weight growth in maternal PH rat offspring, and the pathological changes of the cardiac–cerebral system caused by maternal PH, including enlarged right heart cavity, loss of cardiomyocytes, abnormal heart index, as well as cerebral cortex hypoxia and the inflammatory state as they grew up to a certain extent. The findings show the pathological significance of maternal PH on offspring growth and the cardiac–cerebral development in a rat model, as well as point out the potential treatment target, which may provide a further reference for pregnancy outcomes in women with PH and healthy development of offspring to some extent.

The impact of pulmonary hypertension on outcomes of transcatheter mitral valve replacement in mitral annular calcification.

To assess the impact of pulmonary hypertension (PH) on outcomes of patients with severe mitral annular calcification (MAC) undergoing transcatheter mitral valve replacement (TMVR). PH is associated with poor outcomes after mitral valve surgery. Whether the presence of PH in patients with MAC undergoing (TMVR) is associated with poor outcomes, is unknown. Retrospective evaluation of 116 patients from 51 centers in 11 countries who underwent TMVR with valve in mitral annular calcification (ViMAC) using balloon-expandable aortic transcatheter valves (THVs) from September 2012 to March 2017. Pulmonary artery systolic blood pressure (PASP) by echocardiogram was available in 90 patients. The subjects were stratified based on PASP: No PH = PASP ≤35 mmHg (n = 11); mild to moderate PH = PASP 36-49 mmHg (n = 21) and severe PH = PASP ≥50 mmHg (n = 58). Clinical, procedural, and echocardiographic outcomes were assessed. Mean age was 72.7 (±12.8) years, 59 (65.6%) were female, Society of Thoracic Surgeons score was 15.8 + 11.8% and 90.0% where in New York Heart Association (NYHA) class III-IV. There was no significant difference in all-cause mortality at 30 days (no PH = 27.3%, mild-moderate PH = 19.0%, severe PH = 31.6%; p = 0.55) or at 1 year (no PH = 54.5%, mild-moderate PH = 38.1%, severe PH = 56.1%; p = 0.36). No difference in adverse events, NYHA class or amount of residual mitral regurgitation at 1 year were observed between the groups. This study suggests that the presence of PH in patients with predominantly mitral stenosis with MAC undergoing TMVR does not impact mortality or adverse events. Further studies are needed to fully understand the effect of PH in this group of patients.

Pulmonary hypertension in infants with bronchopulmonary dysplasia: risk factors, mortality and duration of hospitalisation.

Pulmonary hypertension (PH) is a complication of bronchopulmonary dysplasia (BPD) and associated with increased mortality and morbidity. Our aim was to identify, in infants with BPD, the effect of PH on health-care utilisation and health related cost of care. An electronic data recording system was used to identify infants≤32weeks of gestation who developed BPD. PH was classified as early (≤28days after birth) or late (>28days after birth). In the study period, 182 infants developed BPD; 22 (12.1%) developed late PH. Development of late PH was associated with a lower gestational age [24.6 (23.9-26.9) weeks, p=0.001] and a greater need for positive pressure ventilation on day 28 after birth (100%) compared to infants without late PH (51.9%) (odds ratio (OR) 19.5, 95% CI: 2.6-148), p<0.001. Late PH was associated with increased mortality (36.4%) compared those who did not develop late PH (1.9%) after adjusting for gestational age and ventilation duration (OR: 26.9, 95% CI: 3.8-189.4), p<0.001. In infants who survived to discharge, late PH development was associated with a prolonged duration of stay [147 (118-189) days] compared to the infants that did not develop late PH [109 (85-149) days] (p=0.03 after adjusting for gestational age). Infants who had late PH had a higher cost of stay compared to infants with BPD who did not develop late PH (median £113,494 vs. £78,677, p=0.016 after adjusting for gestational age). Development of late PH was associated with increased mortality, a prolonged duration of stay and higher healthcare cost.

Pulmonary Hypertension Is Associated with Poor Outcomes in Patients with Myeloproliferative Neoplasms and Cardiovascular Disease

▪Background: Myeloproliferative neoplasms (MPNs) are a group of disorders of clonal hematopoiesis and include essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). Cardiovascular disease, including atrial fibrillation (AF), heart failure (HF), pulmonary hypertension (PH), and atherosclerotic heart disease, is an underappreciated cause of morbidity and mortality in MPNs. Additionally, MPNs harbor mutations commonly seen in clonal hematopoiesis of indeterminate potential (CHIP) which has been shown to be associated with increased cardiovascular risk. PH has been associated with MPN and MPN-associated PH is classified as group 5 PH according to the World Health Organization. Although studies have shown PH to occur in between 3.8% to 58% of patients with PMF and has been associated with decreased overall survival in PV, its impact on cardiovascular prognosis, including cardiovascular death (CV death), in patients with MPN has been understudied. Our study aims to investigate the prognostic implication of PH in a high risk MPN population, those with cardiovascular disease.Methods: Our study is a single center retrospective cohort study. Using an institutional database, we identified 197 patients with MPN (ET, PV or PMF) who had cardiovascular disease (AF, hospitalization for HF or acute coronary syndrome after MPN diagnosis) and had undergone right heart catheterization (RHC) or transthoracic echocardiography (TTE). PH was defined as either a mean pulmonary artery pressure ≥ 20 mmHg on RHC or estimated right ventricular systolic pressure (RVSP) ≥ 50 mmHg on TTE. Our primary outcome was CV death (death due to pulmonary embolism, myocardial infarction, stroke, arrhythmia, sudden death or HF). Other outcomes of interest included all-cause mortality, HF hospitalization, VTE and arterial thrombosis. Continuous variables were compared using Student's t-test, categorical variables and outcomes were compared with the Fisher exact test. We used a Fine-Gray model to determine the effect of PH on CV death using other causes of death as competing events. To investigate the effect of PH on our outcomes we also used a multivariable logistic regression model using age, sex, MPN type, MPN treatment, arterial and venous thrombosis prior to and after MPN diagnosis, diabetes, prior HF diagnosis, HF hospitalization after MPN diagnosis, AF, hyperlipidemia, leukemic or secondary myelofibrosis transformation, and diabetes as co-variables.Results: There were 92 patients with PH and 105 patients without PH. Median age at MPN diagnosis was higher in PH vs non-PH patients (73 vs 71, p = 0.038). The median time to diagnosis of PH from MPN diagnosis was 69 months (IQR 43, 113). Patients with PH had higher rates of prior HF (54% vs 32%, p = 0.001) and hypertension (83% vs 64%, p = 0.004), but lower rates of AF (64% vs 79%, p = 0.026) compared with patients without PH. MPN types and driver mutations were not statistically significant between PH and non-PH groups. More patients with PH had leukemic or secondary myelofibrosis transformation compared with patients without PH (23% vs 11%, p = 0.037). Patients with PH had higher rates of CV death (35% vs 9%, p < 0.0001), all-cause death (58% vs 37%, p = 0.004), HF hospitalization (73% vs 36%, p < 0.0001) and VTE (25% vs 12%, p = 0.027) but not arterial thrombosis (39% vs 41%, p = 0.88). Cumulative incidence of CV death was higher in PH compared with non-PH patients (Figure 1A, Fine-Gray HR 5.53, 95% CI 2.58-11.85). After multivariable regression, PH was associated with higher odds of CV death (Figure 1B, aOR 6.1, 95% CI 2.2-19.0), VTE (aOR 3.3, 95% CI 2.0-25.5), HF hospitalization (aOR 3.9, 95% CI 1.6-10.2) but not all-cause death (aOR 1.5, 95% CI 0.7-3.2) or arterial thrombosis (aOR 0.9, 95% CI 0.4-1.9), Figure 1B.Conclusions: In patients with MPN and cardiovascular diseases, PH is associated with worse outcomes including CV death, VTE, HF hospitalization and leukemic/secondary myelofibrosis transformation compared with patients without PH. More investigation is needed but our results suggests early screening for PH may be beneficial in this patient population. [Display omitted] DisclosuresNeuberg: Madrigal Pharmaceuticals: Other: Stock ownership; Pharmacyclics: Research Funding. Rosovsky: Janssen: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Inari: Consultancy, Membership on an entity's Board of Directors or advisory committees; Dova: Consultancy, Membership on an entity's Board of Directors or advisory committees. Hobbs: Bayer: Research Funding; Incyte Corporation: Research Funding; Merck: Research Funding; Constellation Pharmaceuticals: Consultancy, Research Funding; Novartis: Consultancy; Celgene/Bristol Myers Squibb: Consultancy; AbbVie.: Consultancy.

Assessment of platelets in patients with pulmonary hypertension

Background: Pulmonary hypertension (PH) occurs due to end result of multifactorial etiology causing significant morbidity and mortality. Platelets are observed to be activated during initiation and progression of disease, platelets indices used as surrogate markers for platelet activation was used in current study to investigate effect of PH on platelets and correlate it with severity of PH.Methods: 104 patients with PH were grouped according to WHO classification depending upon etiology. Blood samples of patients from all groups were collected and investigated for platelet indices, peripheral smear, bleeding time, clotting time and echocardiography assessment to know the severity of pulmonary hypertension. Patients were reviewed after 2 months of appropriate treatment.Results: Prevalence of PH due to chronic lung disease (48.1%) was the most common observation. Thrombocyte count was decreased significantly in all groups of PH with p&lt;0.01. MPV, PDW, P-LCR (platelet-large cell ratio) were observed to be increased with increasing severity for PH. Significant correlation p=0.01 indicated that platelet indices were altered with treatment for PH.Conclusions: Significant reduction was observed in platelet count with increase in platelet indices can be correlated with severity of PH. Hence in rural areas without echo cardiogram facilities, platelet indices can be considered as surrogate markers for early referral of patients to higher centers for further management of PH.

Hemodynamic Characteristics and Outcomes of Pulmonary Hypertension in Patients Undergoing Tricuspid Valve Repair or Replacement

BackgroundThe impact of pulmonary hypertension (PH) on outcomes after surgical tricuspid valve replacement (TVR) and repair (TVr) is unclear. We sought to characterize PH in patients undergoing TVR/TVr, based on invasive hemodynamics and evaluate the effect of PH on mortality. MethodsWe identified 86 consecutive patients who underwent TVR/TVr with invasive hemodynamic measurements within 3 months before surgery. We used Kaplan-Meier survival and restricted mean survival time (RMST) analyses to quantify the effects of PH on survival. ResultsThe mean age was 63 ± 13 years, 59% were female, 45% had TVR, 55% had TVr, 39.5% had isolated TVR/TVr, and 60.5% had TVR/TVr concomitant with other cardiac surgeries). Eighty-six percent of these patients had PH with a mean pulmonary artery pressure of 30 ± 10 mm Hg, pulmonary vascular resistance (PVR) of 2.5 (interquartile range: 1.5-3.9) Wood units (WU), pulmonary arterial compliance of 2.3 (1.6-3.6) mL/mm Hg, and pulmonary arterial elastance of 0.8 (0.6-1.2) mm Hg/mL. Cardiac output was mildly reduced at 4.0 ± 1.4 L/min, with elevated right-atrial pressure (14 ± 12 mm Hg) and pulmonary capillary wedge pressure (19 ± 7 mm Hg). Over a median follow-up of 6.3 years, 22% of patients died. Patients with PVR ≥ 2.5 WU had lower RMST over 5 years compared with patients with PVR < 2.5 WU. ConclusionPH is common in patients undergoing TVR/TVr, with combined pre- and postcapillary being the most common type. PVR ≥ 2.5 WU is associated with lower survival at 5-year follow-up.

Prevalence and outcomes of pulmonary hypertension after percutaneous closure of atrial septal defect: a systematic review and meta-analysis.

Atrial septal defect (ASD) is a common form of congenital heart disease. Significant shunts may increase the risk of developing pulmonary hypertension (PH). We aimed to describe current PH definitions, evaluate PH prevalence and the effect of PH on outcomes in patients undergoing percutaneous ASD closure. EMBASE, MEDLINE and Cochrane databases were systematically searched. Studies reporting PH prevalence or mean systolic pulmonary arterial pressure (sPAP) before and after percutaneous ASD closure in adults were included. We conducted meta-analyses to obtain summary estimates for PH prevalence and mean sPAP. 15 articles with a total of 1073 patients met the eligibility criteria. Studies applied variable PH definitions. PH prevalence and mean sPAP levels decreased in all studies after closure. The pooled PH prevalence decreased from 44% (95% CI 29-60%) to 18% (95% CI 8-27%). The overall standardised mean difference in sPAP was 1.12 (95% CI 0.81-1.44) and 1.62 (95% CI 1.00-2.23) in cohort and case-series studies respectively indicating a large decrease. The pooled standard mean difference among the younger and older patients were different, 1.25 (95% CI 0.78-1.71) and 0.91 (95% CI 0.56-1.27), respectively. A high degree of between-study heterogeneity was noted. Both PH prevalence and mean sPAP decrease after ASD closure. Larger, prospective studies with consistent PH definitions using the recommended measurement modality are warranted.

Mechanics of right ventricular dysfunction in pulmonary arterial hypertension and heart failure with preserved ejection fraction.

Right ventricular (RV) dysfunction is the most important determinant of survival in patients with pulmonary hypertension (PH). The manifestations of RV dysfunction not only include changes in global RV systolic function but also abnormalities in the pattern of contraction and synchrony. The effects of PH on the right ventricle have been mainly studied in patients with pulmonary arterial hypertension (PAH). However, with the demographic shift towards an aging population, heart failure with preserved ejection fraction (HFpEF) has become an important etiology of PH in recent years. There are significant differences in RV mechanics, function and adaptation between patients with PAH and HFpEF (with or without PH), which are related to different patterns of remodeling and dysfunction. Due to the unique features of the RV chamber, its connection with the main pulmonary artery and the pulmonary circulation, an understanding of the mechanics of RV function and its clinical significance is mandatory for both entities. In this review, we describe the mechanics of the pressure overloaded right ventricle. We review the different mechanical components of RV dysfunction and ventricular dyssynchrony, followed by insights via analysis of pressure-volume loop, energetics and novel blood flow patterns, such as vortex imaging. We conduct an in-depth comparison of prevalence and characteristics of RV dysfunction in HFpEF and PAH, and summarize key outcome studies. Finally, we provide a perspective on needed and expected future work in the field of RV mechanics.