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Pulmonary hypertension is associated with increased morbidity and mortality, and growing evidence suggests that even mild elevations in pulmonary artery pressure estimated with echocardiography are linked to increased mortality. In healthy individuals who undergo right heart catheterisation, the average pulmonary artery systolic pressure ranges from 17 mm Hg to 25 mm Hg; on echocardiography, estimated pulmonary artery systolic pressure of more than 30 mm Hg is outside the normal range for most healthy individuals. Increased pulmonary artery systolic pressure (>30 mm Hg) is reported on more than 40% of clinically indicated echocardiograms, often in the presence of metabolic and cardiopulmonary comorbidities, and is associated with a 5-year mortality of 25-40%. However, current guidelines do not sufficiently highlight risk and risk-reduction approaches for the sizable patient population with elevated pulmonary artery pressure who do not have underlying severe pulmonary vascular disease such as pulmonary arterial hypertension. Increased awareness of this frequently reported high-risk echocardiographic finding, and multidisciplinary risk-reduction approaches for patients with metabolic and cardiopulmonary comorbidities and elevated pulmonary artery pressure, are urgently needed.

Purpose In clinical practice, many patients with right heart failure (RHF) have elevated pulmonary artery pressures and increased afterload on the right ventricle (RV). In this study, we evaluated the feasibility of RV augmentation using a soft robotic right ventricular assist device (SRVAD), in cases of increased RV afterload. Methods In nine Yorkshire swine of 65–80 kg, a pulmonary artery band was placed to cause RHF and maintained in place to simulate an ongoing elevated afterload on the RV. The SRVAD was actuated in synchrony with the ventricle to augment native RV output for up to one hour. Hemodynamic parameters during SRVAD actuation were compared to baseline and RHF levels. Results Median RV cardiac index (CI) was 1.43 (IQR, 1.37–1.80) L/min/m2 and 1.26 (IQR 1.05–1.57) L/min/m2 at first and second baseline. Upon PA banding RV CI fell to a median of 0.79 (IQR 0.63–1.04) L/min/m2. Device actuation improved RV CI to a median of 0.87 (IQR 0.78–1.01), 0.85 (IQR 0.64–1.59) and 1.11 (IQR 0.67–1.48) L/min/m2 at 5 min (p = 0.114), 30 min (p = 0.013) and 60 (p = 0.033) minutes respectively. Statistical GEE analysis showed that lower grade of tricuspid regurgitation at time of RHF (p = 0.046), a lower diastolic pressure at RHF (p = 0.019) and lower mean arterial pressure at RHF (p = 0.024) were significantly associated with higher SRVAD effectiveness. Conclusions Short-term augmentation of RV function using SRVAD is feasible even in cases of elevated RV afterload. Moderate or severe tricuspid regurgitation were associated with reduced device effectiveness.

Background: Despite being controversial, left ventricular venting is still used to facilitate valvular heart surgeries and prevent distention. The classic way to vent the left ventricle is via the right superior pulmonary vein, which has many reported complications. Objective: We aimed to evaluate the effectiveness of pulmonary artery venting in patients undergoing mitral valve surgery who have elevated pulmonary artery pressure. Patients and Methods: 100 patients undergoing isolated mitral valve replacement, and having elevated pulmonary artery pressure were recruited in Cairo University Hospitals. They were divided into 2 groups; group 1 had pulmonary artery venting, and group 2 had no plmonary artery venting. Both groups were compared for preoperative, operative and postoperative variables. Results: Patients were divided into 2 groups; group 1 comprised 51 patients and had pulmonary artery venting, and group 2 comprised 49 patients and had no pulmonary artery venting. Both groups had similar preoperative characteristics, with group 1 having 14 minutes shorter cross clamping time (p value = 0.001), and 0.6 days shorter ICU stay (p value = 0.002), mean hospital stay was 6.4 ± 1.7 in group 1 and 8.7 ± 2.2 in group 2 (p value = 0.001). Conclusion: Using pulmonary artery venting during open heart surgery for mitral valve replacement, in patients with elevated pulmonary artery pressure is beneficial, facilitates the surgical procedure, and is associated with shorter ICU and hospital stay.

BackgroundIt is widely recognized that metabolic disorder is associated with pulmonary hypertension (PH). It is known that hypoxia-induced elevated pulmonary artery pressure in mice returns to normal pressure during reoxygenation. However, it is still unclear how metabolic disorder affects the reverse remodeling of pulmonary arteries. In this study, we investigated the effects of high-fat diet (HFD) on the decrease in pulmonary artery pressure and reverse remodeling of pulmonary arteries in mice with hypoxia-induced PH.MethodsWe used female C57BL/6 mice aged 8 weeks. After being exposed to hypoxia (10% oxygen for four weeks) to induce PH, the mice were returned to normoxic conditions and randomized into a normal diet (ND) group and HFD group. Both groups were fed with their respective diets for 12 weeks.ResultsThe Fulton index and right ventricular systolic pressure measured by a micro-manometer catheter were significantly higher in the HFD group than in the ND group at 12 weeks after reoxygenation. The medial smooth muscle area was larger in the HFD group. Caspase-3 activity in the lung tissue of the HFD group was decreased, and the apoptosis of pulmonary smooth muscle cells was suppressed after reoxygenation. Moreover, the expression levels of peroxisome proliferator-activated receptor-γ and apelin were lower in the HFD group than in the ND group.ConclusionsThe results suggest that metabolic disorder may suppress pulmonary artery reverse remodeling in mice with hypoxia-induced PH during reoxygenation.

Compare the intraventricular hemodynamics of 60 females with systemic lupus erythematosus (SLE) and 61 healthy female controls, and determine cardiac function changes using vector flow mapping (VFM).To determine the effect of pulmonary artery pressure changes on left ventricular function, SLE patients were divided into a normal pulmonary artery pressure group (S1, n=24) and an elevated pulmonary artery pressure group (S2, n=36). The energy loss (EL) at each segment of the left ventricular chamber (total, basal, middle, and apical segments) during each period of the cardiac cycle (isovolumic contraction, rapid ejection, rapid filling, reduced filling, atrial contraction) was determined.The S1 group had significantly more vortices than the control group during the rapid ejection, rapid filling, and atrial contraction periods (p0.01), and the maximum vortex areas in the S1 and S2 groups were smaller than in the control group during rapid filling and atrial contraction periods (p0.05). Compared with the control group, the S2 group had greater EL during the systole and diastole periods (p0.01). EL in the S1 group was significantly greater than in the control group during systole (p0.01). During the rapid filling period, the EL was positively correlated with septal E' (r=0.784, p0.01), and during the atrial contraction period, EL was positively correlated with septal E/e' (r=0.812, p0.01) and A (r=0.715, p0.01).VFM of patients with SLE can comprehensively, rapidly, and efficiently evaluate changes of myocardial mechanics and intracardiac hemodynamics and provide quantitative analysis of complex intracardiac blood flow. Key points • Vector flow mapping (VFM) is a new non-invasive ultrasound technique that evaluates changes of myocardial mechanics and intracardiac hemodynamics, and provides quantitative analysis of complex intracardiac blood flow. • This study showed that vortex and energy loss may provide more sensitive detection of cardiac dysfunction than conventional echocardiographic indexes in patients with systemic lupus erythematosus.

Patients with mitral valve prolapse (MVP), undergoing early surgery for severe regurgitation, are usually characterized by a low degree of right chambers’ remodeling. In this selected population, the mechanisms leading to tricuspid annular (TA) dilatation (TAD) are not well understood. In this setting, we aimed to evaluate, using three-dimensional echocardiography (3DE), how right chambers affect TA size and might contribute to functional tricuspid regurgitation (FTR) progression. We studied 159 patients treated with early isolated surgery for MVP, characterized by: sinus rhythm; normal biventricular function; normal or elevated pulmonary artery pressure; tricuspid regurgitation (TR) ≤ mild; no concomitant cardiac disease. All patients reached a 3-year echocardiographic follow-up. Based on two-dimensional echocardiography, patients were divided in Group 1 (N = 68, 43%, TAD, TA ≥ 21 mm/m2) and Group 2 (N = 91, 57%, no TAD, TA

Pulmonary arterial hypertension (PAH) is associated with increased inflammation and abnormal vascular remodeling. Astragaloside IV (ASIV), a purified small molecular saponin contained in the well‑know herb, Astragalus membranaceus, is known to exert anti‑inflammatory and anti‑proliferation effects. Thus, the present study investigated the possible therapeutic effects of ASIV on monocrotaline (MCT)‑induced PAH. Rats were administered a single intraperitoneal injection of MCT (60 mg/kg), followed by treatment with ASIV at doses of 10 and 30 mg/kg once daily for 21 days. Subsequently, right ventricle systolic pressure, right ventricular hypertrophy and serum inflammatory cytokines, as well as pathological changes of the pulmonary arteries, were examined. The effects of ASIV on the hypoxia‑induced proliferation and apoptotic resistance of human pulmonary artery smooth muscle cells (HPASMCs) and the dysfunction of human pulmonary artery endothelial cells (HPAECs) were evaluated. MCT elevated pulmonary artery pressure and promoted pulmonary artery structural remodeling and right ventricular hypertrophy in the rats, which were all attenuated by both doses of ASIV used. Additionally, ASIV prevented the increase in the TNF‑α and IL‑1β concentrations in serum, as well as their gene expression in lung tissues induced by MCT. In in vitro experiments, ASIV attenuated the hypoxia‑induced proliferation and apoptotic resistance of HPASMCs. In addition, ASIV upregulated the protein expression of p27, p21, Bax, caspase‑9 and caspase‑3, whereas it downregulated HIF‑1α, phospho‑ERK and Bcl‑2 protein expression in HPASMCs. Furthermore, in HPAECs, ASIV normalized the increased release of inflammatory cytokines and the increased protein levels of HIF‑1α and VEGF induced by hypoxia. On the whole, these results indicate that ASIV attenuates MCT‑induced PAH by improving inflammation, pulmonary artery endothelial cell dysfunction, pulmonary artery smooth muscle cell proliferation and resistance to apoptosis.

Accurate diagnosis of pulmonary hypertension (PH) is crucial to ensure that patients receive timely treatment. We hypothesized that application of artificial intelligence (AI) to the chest X-ray (CXR) could identify elevated pulmonary artery pressure (PAP) and stratify the risk of heart failure hospitalization with PH. We retrospectively enrolled a total of 900 consecutive patients with suspected PH. We trained a convolutional neural network to identify patients with elevated PAP (> 20 mmHg) as the actual value of PAP. The endpoints in this study were admission or occurrence of heart failure with elevated PAP. In an independent evaluation set for detection of elevated PAP, the area under curve (AUC) by the AI algorithm was significantly higher than the AUC by measurements of CXR images and human observers (0.71 vs. 0.60 and vs. 0.63, all p

Pulmonary hypertension (PH) is a well-known complication of sarcoidosis, defined by a mean pulmonary artery pressure of ≥25 mm Hg. Since both PH and sarcoidosis are rare diseases, data on sarcoidosis-associated PH (SAPH) is retrieved mostly from small retrospective studies. Estimated prevalence of SAPH ranges from 3% in patients referred to a tertiary center up to 79% in patients awaiting lung transplant. Most patients with SAPH show advanced parenchymal disease as the underlying mechanism. However, some patients have disproportional elevated pulmonary artery pressure, and PH can occur in sarcoidosis patients without parenchymal disease. Other mechanisms such as vascular disease, pulmonary embolisms, postcapillary PH, extrinsic compression, and other sarcoidosis-related comorbidities might contribute to SAPH. The diagnosis of PH in sarcoidosis is challenging since symptoms and signs overlap. Suspicion can be raised based on symptoms or tests, such as pulmonary function tests, laboratory findings, electrocardiography, or chest CT. PH screening mainly relies on transthoracic echocardiography. Right heart catheterization should be considered on a case-by-case basis in patients with clinical suspicion of PH, taking into account clinical consequences. Treatment options are considered on patient level in a PH expert center, and might include oxygen therapy, immunosuppressive, or PH-specific therapy. However, qualitative evidence is scarce. Furthermore, in a subset of patients, interventional therapy or eventually lung transplant can be considered. SAPH is associated with high morbidity. Mortality is higher in sarcoidosis patients with PH compared with those without PH, and increases in patients with more advanced stages of sarcoidosis and/or PH.

Background: Sickle Cell Anaemia (SCA) is the most common inherited disorder in Nigeria. Pulmonary Hypertension (PH) is a known complication of SCA that commences from childhood and progresses as they grow older. Aim: To determine the prevalence and predictors of elevated pulmonary artery pressure (PAP) in children with SCA. Study Design: This is an analytical cross-sectional study. Methods: Three hundred subjects with SCA in steady state and 300 HbAA controls, aged 6 months – 15 years, were enrolled into the study. Children with SCA were recruited by simple random sampling, from the Paediatric Sickle Cell Clinic, Usmanu Danfodiyo University Teaching Hospital, Sokoto. All the children had clinical evaluation, echocardiography, full blood count and reticulocyte count. Pulmonary artery systolic pressure (PASP) and mean pulmonary artery pressure (MPAP) were determined by measurement of tricuspid regurgitant velocity (TRV) and mean gradient (MG) respectively. Results: Seventy-two children with SCA (24.0%) had elevated PAP (defined as TRV ≥ 2.5 m /s) while only 9 (3.0%) had pulmonary hypertension (defined as MPAP ≥ 25 mmHg). Older age (O.R = 1.03, p < 0.001), high systolic blood pressure (O.R = 1.2, p = 0.01), and high reticulocyte count (O.R = 1.33, p = 0.04) were weakly associated with increased likelihood of elevated PAP. Normal pulse oxygen saturation (SPO2 ≥ 95%, O.R = 0.4, p = 0.002) and normal heart sounds on auscultation (O.R = 0.2, p = 0.04) were associated with a reduced likelihood of elevated PAP. Presence of left parasternal heave (O.R = 8.4, p = 0.001) significantly predicted elevated PAP in children with SCA. Conclusion: PH occurs as a complication in children with SCA and certain clinical and laboratory parameters do predict this complication in children.

Purpose: In clinical practice, many patients with right heart failure (RHF) have elevated pulmonary artery pressures and increased afterload on the right ventricle (RV). In this study, we evaluated the feasibility of RV augmentation using a soft robotic right ventricular assist device (SRVAD), in cases of increased RV afterload. Methods: In nine Yorkshire swine of 65-80 kg, a pulmonary artery band was placed to cause RHF and maintained in place to simulate an ongoing elevated afterload on the RV. The SRVAD was actuated in synchrony with the ventricle to augment native RV output for up to one hour. Hemodynamic parameters during SRVAD actuation were compared to baseline and RHF levels. Results: Median RV cardiac index (CI) was 1.43 (IQR, 1.37-1.80) L/min/m2 and 1.26 (IQR 1.05-1.57) L/min/m2 at first and second baseline. Upon PA banding RV CI fell to a median of 0.79 (IQR 0.63-1.04) L/min/m2. Device actuation improved RV CI to a median of 0.87 (IQR 0.78-1.01), 0.85 (IQR 0.64-1.59) and 1.11 (IQR 0.67-1.48) L/min/m2 at 5 min (p = 0.114), 30 min (p = 0.013) and 60 (p = 0.033) minutes respectively. Statistical GEE analysis showed that lower grade of tricuspid regurgitation at time of RHF (p = 0.046), a lower diastolic pressure at RHF (p = 0.019) and lower mean arterial pressure at RHF (p = 0.024) were significantly associated with higher SRVAD effectiveness. Conclusions: Short-term augmentation of RV function using SRVAD is feasible even in cases of elevated RV afterload. Moderate or severe tricuspid regurgitation were associated with reduced device effectiveness.

ObjectiveTo determine the prevalence of cardiac abnormalities and their relationship to markers of myocardial injury and mortality in patients admitted to hospital with COVID-19.MethodsA retrospective and prospective observational study of inpatients referred for transthoracic echocardiography for suspected cardiac pathology due to COVID-19 within a London NHS Trust. Echocardiograms were performed to assess left ventricular (LV), right ventricular (RV) and pulmonary variables along with collection of patient demographics, comorbid conditions, blood biomarkers and outcomes.ResultIn the predominant non-white (72%) population, RV dysfunction was the primary cardiac abnormality noted in 50% of patients, with RV fractional area change ConclusionsIn this predominantly non-white population hospitalised with COVID-19, the most common cardiac pathology was RV dysfunction which is associated with both LV systolic dysfunction and elevated pulmonary artery pressure. The latter two, not RV dysfunction, were associated with mortality.

The spread of the novel coronavirus 2019 (COVID‐19) has caused a global pandemic. The disease has spread rapidly, and research shows that COVID‐19 can induce long‐lasting cardiac damage. COVID‐19 can result in elevated cardiac biomarkers indicative of acute cardiac injury, and research utilizing echocardiography has shown that there is mechanical dysfunction in these patients as well, especially when observing the isovolumic, systolic, and diastolic portions of the cardiac cycle. The purpose of this study was to present two case studies on COVID‐19 positive patients who had their cardiac mechanical function assessed every day during the acute period to show that cardiac function in these patients was altered, and the damage occurring can change from day‐to‐day. Participant 1 showed compromised cardiac function in the systolic time, diastolic time, isovolumic time, and the calculated heart performance index (HPI), and these impairments were sustained even 23 days post‐symptom onset. Furthermore, Participant 1 showed prolonged systolic periods that lasted longer than the diastolic periods, indicative of elevated pulmonary artery pressure. Participant 2 showed decreases in systole and consequently, increases in HPI during the 3 days post‐symptom onset, and these changes returned to normal after day 4. These results showed that daily observation of cardiac function can provide detailed information about the overall mechanism by which cardiac dysfunction is occurring and that COVID‐19 can induce cardiac damage in unique patterns and thus can be studied on a case‐by‐case basis, day‐to‐day during infection. This could allow us to move toward more personalized cardiovascular medical treatment., Daily assessments of mechanical cardiac function provides insights to impairments and potential mechanisms in cardiac function following COVID‐19. A young participant with no previous medical history showed altered cardiac function which varied from day to day, and this damage was sustained for up to 3 weeks, whereas an older participant showed acute cardiac damage which was sustained for 3 days before returning to normal.

Pediatric pulmonary hypertension (PPH) is a multifactorial disease with diverse etiologies and presenting features. Pulmonary hypertension (PH), defined as elevated pulmonary artery pressure, is the presenting feature for several pulmonary vascular diseases. It is often a hidden component of other lung diseases, such as cystic fibrosis and bronchopulmonary dysplasia. Alterations in lung development and genetic conditions are an important contributor to pediatric pulmonary hypertensive disease, which is a distinct entity from adult PH. Many of the causes of pediatric PH have prenatal onset with altered lung development due to maternal and fetal conditions. Since lung growth is altered in several conditions that lead to PPH, therapy for PPH includes both pulmonary vasodilators and strategies to restore lung growth. These strategies include optimal alveolar recruitment, maintaining physiologic blood gas tension, nutritional support, and addressing contributing factors, such as airway disease and gastroesophageal reflux. The outcome for infants and children with PH is highly variable and largely dependent on the underlying cause. The best outcomes are for neonates with persistent pulmonary hypertension (PPHN) and reversible lung diseases, while some genetic conditions such as alveolar capillary dysplasia are lethal. © 2021 American Physiological Society. Compr Physiol 11:2135-2190, 2021.

Pulmonary hypertension (PH) includes multiple diseases that share as common characteristic an elevated pulmonary artery pressure and right ventricular involvement. Sex differences are observed in practically all causes of PH. The most studied type is pulmonary arterial hypertension (PAH) which presents a gender bias regarding its prevalence, prognosis, and response to treatment. Although this disease is more frequent in women, once affected they present a better prognosis compared to men. Even if estrogens seem to be the key to understand these differences, animal models have shown contradictory results leading to the birth of the estrogen paradox. In this review we will summarize the evidence regarding sex differences in experimental animal models and, very specially, in patients suffering from PAH or PH from other etiologies.

Noonan syndrome is known to have various cardiovascular defects, which include pulmonary artery stenosis. Pulmonary artery stenosis is characterized by obstruction of pulmonary artery blood flow that can cause elevated pulmonary artery pressure and ventilation-perfusion inequality, which can cause dyspnea on exertion and eventually, heart failure. Although the etiology of pulmonary artery stenosis related to congenital diseases is still unknown, balloon pulmonary angioplasty has being reported to be effective to selected patients with Alagille and Williams syndromes, but not from Noonan syndrome despite of modest prevalence of pulmonary artery stenosis. Here, we report the first Noonan syndrome patient with pulmonary artery stenosis who underwent successful balloon pulmonary angioplasty. The strategy used in balloon pulmonary angioplasty was planned with careful morphologic evaluation by computed tomographic angiography, and performed with scoring balloons in a graded approach with multiple sessions. After balloon pulmonary angioplasty, we confirmed maintained dilation of lesions and symptom alleviation, suggesting that balloon pulmonary angioplasty can be performed safely on pulmonary artery stenosis in a Noonan syndrome patient.

Background: The right ventricle performance is very important in the prognosis of the patients with intracardiac shunts. Development of RV failure is associated with higher mortality. It can be directly related to the shunt itself or indirectly associated with elevated pulmonary artery pressure. Objective: The aim of this work wasto assess the diastolic and the systolic performance of the right ventricle in patients with different types of intracardiac shunts by the Echocardiography in comparison with the normal population. Patients and methods: Our study included 132 patients undergoing echocardiography in the Outpatient Clinic of Tanta University Hospital. The study was conducted starting from 1st of February 2018 to 28th of February 2019. The study included 63 female and 69 male patients. Their age ranged from 1 month to 49 years old. RV diastolic and systolic function were assessed in the four groups using MPI, Stroke work, longitudinal RV strain rate. Results: Our results showed higher values of the parameters measured in the atrial septal defects (ASD) patients' group compared to the normal subjects and the other intracardiac shunt's patients. Also, ASD's patients were associated with higher pulmonary artery pressure values and worse RV function parameters in general. Conclusion: We concluded that the new echocardiographic measures are good and reliable tool to assess the right ventricle function in the patients with intracardiac shunts. Additionally, ASD’ patients are associated with worse outcome especially if they develop elevated pulmonary artery pressure.

Pulmonary hypertension is a life-threatening illness with debilitating physical and emotional consequences. The progression of this devastating disease is characterized by a continuous increase in pulmonary vascular resistance, which results in elevated pulmonary artery pressure and leads to right heart failure. Treatment is focused on targeting the underlying complex etiology via the endothelin, prostacyclin, and nitric oxide (NO) pathways. Emergence of new treatments over the past 2 decades has led to improvement in the functional status and time to clinical worsening. Even with recent advances, outcomes remain suboptimal. Phosphodiesterase-5 (PDE-5) inhibitors, such as sildenafil, were approved for treatment of pulmonary arterial hypertension (PAH) by the Food and Drug Administration (FDA) in 2005, which holds promise in improving quality of life and therefore making this class of medications effective palliative therapy agents. In this review, we summarize the emergence of sildenafil as a treatment for PAH and its role as palliative therapy.

Objective This prospective study was undertaken to evaluate right ventricular function and pulmonary arterial compliance (PAC; ratio of stroke volume to pulse pressure) at rest and during exercise in patients with systemic sclerosis (SSc) with normal mean pulmonary artery pressure (PAP), patients with SSc with mildly elevated mean PAP, and patients with SSc with manifest pulmonary hypertension (PH). Methods Patients with SSc (n = 112) underwent clinical assessment and right-sided heart catheterization at rest and during exercise and were divided into 3 groups according to their resting mean PAP values: normal mean PAP (≤20 mm Hg), mildly elevated mean PAP (21-24 mm Hg), and PH (mean PAP ≥25 mm Hg). Results were compared between groups by analysis of variance followed by post hoc Student's t-test. Results Compared to patients with normal mean PAP, patients with mildly elevated mean PAP had a lower 6-minute walking distance (P = 0.008), lower cardiac index (P = 0.027) and higher pulmonary vascular resistance (P = 0.0002) during exercise, and lower PAC at rest (P = 0.016) and different stages of exercise (P = 0.033 for 25W and P = 0.024 for 75W). Conclusion The results of this study suggest that impaired 6-minute walking distance in SSc patients with mildly elevated mean PAP might be caused by reduced PAC during exercise and reduced right ventricular output reserve, presumably due to impaired coupling between the right ventricle and the pulmonary vasculature. These findings provide further evidence of the clinical relevance of mildly elevated mean PAP in patients with SSc.

Chronic hypoxia-induced sustained pulmonary vasoconstriction and vascular remodeling lead to mild-to-moderate elevation of pulmonary artery pressure in high-altitude residents. However, in some of them, severe pulmonary hypertension may develop. Besides hypoxia, high-altitude residents also face other environmental challenges such as low ambient temperatures. We describe a case of a 49-year-old woman of Kyrgyz ethnicity with abnormally increased pulmonary artery pressure, revealed by Doppler echocardiography. Significantly elevated pulmonary artery pressure was detected in late winter and this was not associated with right ventricular hypertrophy or right ventricular dysfunction. Repeat echocardiography performed in late summer disclosed a significant attenuation of pulmonary artery pressure elevation, with no changes in right ventricular performance parameters. This case illustrates that, in susceptible individuals, long-term cold exposure could induce an abnormal pulmonary artery pressure rise, which can be reversed during warm seasons as in our patient. In certain circumstances, however, additional factors could contribute to a sustained pulmonary artery pressure increase and the development of persistent pulmonary hypertension, which often leads to right heart failure and premature death.

Study objective Pulmonary arterial hypertension is commonly seen in children with left to right intracardiac shunts and affects the outcomes of cardiac surgery. Our study aimed to compare the efficacy of inhaled levosimendan (LS) versus intravenous LS in reducing elevated pulmonary artery pressure (PAP) in children scheduled for cardiac surgery. Design Non-inferiority, prospective, randomized, blinded, controlled study. Setting Operative room and intensive care unit (ICU), institutional children's hospital of Mansoura Faculty of Medicine, Egypt. Patients 50 patients of either sex, aged 1 to 5 years undergoing surgical repair of intracardiac left to right shunt complicated by pulmonary hypertension were recruited for the study. Interventions In the intravenous LS group, patients received intravenous infusion of LS a rate of 0.1 μg/kg/min and in the inhaled LS group, LS (36 μg/kg/6 h) was delivered by nebulization. Measurements The primary endpoint was systolic PAP, while the secondary endpoints were the heart rate, mean arterial blood pressure, dose of norepinephrine, time to extubation and ICU length of stay. Main results Both intravenous and inhaled routes of LS similarly reduced the high systolic PAP over all time points of measurement and intravenous LS was associated with higher heart rate, lower arterial pressure and the need for a higher dose of norepinephrine than the inhaled LS. Conclusion Inhalation of LS is non-inferior to intravenous LS in reducing high PAP in children who underwent on-pump cardiac surgery and it is associated with less tachycardia and hypotension with reduced need for vasoactive drugs.

This study was to explore the application and effect of three-dimensional (3D) images of the esophagus in the treatment of atrial septal defect (ASD) combined with tricuspid regurgitation (TR) surgery under the processing of marching cubes (MC) image reconstruction algorithm. The MC image reconstruction algorithm was improved as the optimized MC image reconstruction algorithm. 100 patients who had successfully undergone the ASD combined with TR surgery in the hospital from January 2017 to December 2019 were selected as the research objects and grouped based on size of the defect. The preoperative and postoperative conditions of the patients were analyzed with the MC image reconstruction algorithm. Compared with the traditional MC image algorithm, the optimized MC was advanced with less running time and fewer fixed points ( P < 0.05 ). There were significant differences in TR of all ASD patients after the surgery ( P < 0.05 ), and the TR of all patients showed obvious declines from the 1st day to 30th day after surgery and gradually stabilized from the 3rd month to the 6th month after surgery. Compared with patients with normal pulmonary artery pressure, the amount of TR in patients with elevated pulmonary artery pressure increased significantly, and the difference was statistically significant ( P < 0.05 ). In addition, the improvement of TR after occlusion was correlated with the preoperative ASD of the patient. The optimized MC algorithm had been improved greatly in the number of fixed points and running time. The analysis using the optimized MC algorithm showed that ASD patients generally suffered different degrees of TR, TR increased with the increase of the defect, and good effect could be achieved in surgery of all kinds of ASD patients.

Phenylalanine levels are associated with pulmonary hypertension in metabolic profiling clinical studies. However, the pathophysiological role of phenylalanine on pulmonary circulation is still unclear. We experimentally addressed the direct impact of phenylalanine on pulmonary circulation in rats and explored the underlying molecular pathway. Phenylalanine was injected intraperitoneally into Sprague-Dawley rats (400 mg/100 g body wt) as a single dose or daily in a chronic manner for 2, 3, and 4 wk. Chronic injection of phenylalanine induced pulmonary hypertension with time-dependent severity, evidenced by elevated pulmonary artery pressure and pulmonary vascular resistance as well as pulmonary artery and right ventricular hypertrophy. Using tandem mass spectrometry analysis, we found a quick twofold increase in blood level of phenylalanine 2 h following injection. This increase led to a significant accumulation of phenylalanine in lung after 4 h, which remained sustained at up to a threefold increase after 4 wk. In addition, a cellular thermal shift assay with lung tissues from phenylalanine-injected rats revealed the binding of phenylalanine to the calcium-sensing receptor (CaSR). In vitro experiments with cultured pulmonary arterial smooth muscle cells showed that phenylalanine activated CaSR, as indicated by an increase in intracellular calcium content, which was attenuated or diminished by the inhibition or knockdown of CaSR. Finally, the global knockout or lung-specific knockdown of CaSR significantly attenuated phenylalanine-induced pulmonary hypertension. Chronic phenylalanine injection induces pulmonary hypertension through binding to CaSR and its subsequent activation. Here, we demonstrate a pathophysiological role of phenylalanine in pulmonary hypertension through the CaSR. This study provides a novel animal model for pulmonary hypertension and reveals a potentially clinically significant role for this metabolite in human pulmonary hypertension as a marker, a mediator of disease, and a possible therapeutic target.

Purpose Limited data exist on the utility of ultrasonographic evaluation of inferior vena cava (IVC) in acute respiratory distress syndrome (ARDS). We studied the value of IVC diameter in assessing cardio-circulatory performance in ARDS using strain echocardiography. Materials and methods Retrospective cross-sectional analysis of Doppler echocardiograms of patients with moderate-severe ARDS was performed. Right ventricle (RV) parameters, IVC diameter, and left ventricle (LV) systolic and diastolic parameters were collected. RV free wall strain (RVFWS) and LV global longitudinal strain (LVGLS) were calculated. Results Fifty-one patients were dichotomized into two groups: with IVC > 2.1 cm (dilated) and with IVC ≤ 2.1 cm (nondilated). The dilated IVC group presented worse hypoxemic profile, hypotension, and poor perfusion markers. No significant associations with positive end-expiratory pressure or lung mechanics were observed. Dilated IVC was associated with impaired RV function, high central venous pressure, elevated pulmonary artery pressure, and LV systolic and diastolic dysfunctions. Strongest predictors of a dilated IVC were RVFWS, LVGLS, and tissue Doppler mitral annular early diastolic velocity. Dilated IVC predicted a global cardiac dysfunction defined by strain echocardiography (GCDS) with high sensitivity and specificity. Conclusions In ARDS, strain echocardiography analyses demonstrated that a dilated IVC is associated with GCDS and impaired hemodynamics independent of lung mechanics. A dilated IVC should be considered a marker of circulatory distress, signaling the potential necessity for improved hemodynamic optimization.

Heart failure with preserved ejection fraction (HFpEF) is increasingly prevalent and represents more than half of all heart failure cases. It is defined by the presence of heart failure signs and symptoms, identification of cardiac structural abnormalities leading to high left ventricular filling pressures, and an EF > 50%. Common imaging findings in HFpEF include left ventricular hypertrophy, diastolic dysfunction, left atrial enlargement, and elevated pulmonary artery pressure (> 35 mm Hg). Echocardiography is the primary imaging modality for diagnosing HFpEF. It can be complemented by cardiac magnetic resonance (CMR) when further characterization is needed. Advances like real-time 3-dimensional echocardiography and speckle-tracking derived strain, as well as tissue characterization by CMR, have furthered our understanding of the mechanisms and aided in making the diagnosis of a diverse group of conditions that can present as HFpEF. This review aims to touch upon the imaging methods of characterizing HFpEF and discuss their role in specific disease entities.

Pulmonary hypertension (PH) comprises a group of pathophysiological syndromes characterized by elevated pulmonary artery pressure and pulmonary vascular resistance, which lead to right ventricular overload, and even right heart failure. PH has a poor prognosis and severely leads to a decline in quality of life. Historically, patients with PH were advised to limit their physical activity. However, an increasing number of studies have reported the safety and efficacy of exercise rehabilitation training in PH. This review briefly examined and summarized the effects of exercise rehabilitation training on PH patients reported in the recent literature. The findings of the reviewed studies indicate that exercise rehabilitation training in PH patients has beneficial effects in terms of exercise capacity and quality of life, vascular and right ventricle remodelling, inflammatory response, muscular function and oxidative stress. However, the underlying mechanisms and appropriate exercise strategies (e.g. the duration and intensity of exercise) still need to be explored. In conclusion, exercise rehabilitation training of the appropriate intensity and frequency can improve the prognosis and quality of life of PH patients. The training should be monitored by professional staff and be provided as an adjunct to pharmacological treatment. Larger clinical trials are required to confirm the safety and efficacy of exercise rehabilitation training in PH.

Pulmonary hypertension (PH) is a pulmonary vascular disease characterized by pulmonary arterial remodeling and vasoconstriction leading to elevated pulmonary artery pressure and, ultimately, right heart failure. So far, few cases of COVID-19 disease in patients with PH have been reported. Caution is warranted in interpreting this observation as data are evolving and several factors may influence the number of reported cases of PH and COVID-19. Social distancing and quarantine could play a role, especially for patients with chronic diseases who might be more vigilant of their potential for respiratory infection. In addition, PH is a rare disease, and because testing is not universal, we could be underestimating the number of cases. Other hypothetical factors to consider are the underlying pathophysiology of PH and the medications used to treat PH and their implications in COVID-19.

Left ventricular assist devices (LVAD) are increasingly implanted in advanced heart failure patients to improve survival and quality of life either as a bridge to transplant, bridge to recovery or as destination therapy. LVAD therapy is often accompanied by a profound lowering of pulmonary artery pressure due to mechanical unloading of the left ventricle. Persistent pulmonary hypertension (PH) after LVAD implantation increases the risk of right ventricular failure (RVF). In this context pulmonary vasodilators have been implemented: a) as a strategy to reduce afterload and wean patients with RVF from inotropes in the early postoperative period, b) as long-term therapy aiming to optimize right heart hemodynamics and prevent late RVF and c) in order to lower persistently elevated pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) after LVAD and enable candidacy for heart transplantation. However, considerable uncertainty exists regarding the risks and benefits of these strategies and practices vary widely among institutions. This article provides an overview of the available evidence and existing recommendations regarding the use of pulmonary vasodilators in LVAD recipients.

Aim: to evaluate pulmonary artery stiffness and right ventricular function to predict early RV impairment in obstructive sleep apnea (OSA). We also aimed to assess the use of anticoagulants in patients with elevated pulmonary artery pressure and OSA.Patients and methods: this study was performed on one hundred cases with OSA who did polysomnography study detecting the complete cessation of respiration and hypoventilation episodes, then estimation of serum fibrinogen, platelets, hepatic and renal functions and blood sugar, conventional echocardiography to measure right ventricular ejection fraction (RVEF), tricuspid annular plane systolic excurtion (TAPSE), myocardial performance index (MPI), fractional area change (FAC), linear diameters of right ventricular inflow tract (RVOT), right ventricular (RV) free wall thickness, Doppler assessment of pulmonary artery stiffness (PAS) and speckle tracking echocardiography (STE) .Results: There was a highly noticed difference among the study groups regarding Fibrinogen, platelet count, RVEF, TAPSE, GLS and PAS. There was a positive relation between fibrinogen and apnea-hypopna index (AHI) (r= 0.686, p< 0.001), a positive relation between PAS and AHI (r= 0.515, p< 0.001), a negative relation between RVEF and AHI (r= -0.639, p< 0.001) and a negative relation between GLS and AHI (r=-0.663, p< 0.001). We found that GLS was important with PAS for prediction of RV failure.Conclusion: OSA patients may have a hidden RV systolic impairment detected by STE. PAS may contribute to the development of RV impairment. Elevated fibrinogen is important risk factor for cardiovascular pathology and may direct attention for starting anticoagulation in OSA patients.

Background: In pulmonary hypertension subgroups, elevated pulmonary vascular resistance (PVR) of 3·0 Wood units or more is associated with poor prognosis. However, the spectrum of PVR risk in pulmonary hypertension is not known. To address this area of uncertainty, we aimed to analyse the relationship between PVR and adverse clinical outcomes in pulmonary hypertension. Methods: We did a retrospective cohort study of all patients undergoing right heart catheterisation (RHC) in the US Veterans Affairs health-care system (Oct 1, 2007–Sep 30, 2016). Patients were included in the analyses if data from a complete RHC and at least 1 year of follow-up were available. Both inpatients and outpatients were included, but individuals with missing mean pulmonary artery pressure (mPAP), pulmonary artery wedge pressure, or cardiac output were excluded. The primary outcome measure was time to all-cause mortality assessed by the Veteran Affairs vital status file. Cox proportional hazards models were used to assess the association between PVR and outcomes, and the mortality hazard ratio was validated in a RHC cohort from Vanderbilt University Medical Center (Sept 24, 1998–June 1, 2016). Findings: The primary cohort (N=40 082; 38 751 [96·7%] male; median age 66·5 years [IQR 61·1–73·5]; median follow-up 1153 days [IQR 570–1971]), included patients with a history of heart failure (23 201 [57·9%]) and chronic obstructive pulmonary disease (13 348 [33·3%]). We focused on patients at risk for pulmonary hypertension based on a mPAP of at least 19 mm Hg (32 725 [81·6%] of 40 082). When modelled as a continuous variable, the all-cause mortality hazard for PVR was increased at around 2·2 Wood units compared with PVR of 1·0 Wood unit. Among patients with a mPAP of at least 19 mm Hg and pulmonary artery wedge pressure of 15 mm Hg or less, the adjusted hazard ratio (HR) for mortality was 1·71 (95% CI 1·59–1·84; p

OBJECTIVE To describe a subset of atrial septal defect (ASD) with severe pulmonary hypertension (PHT) that is suitable for closure. BACKGROUND As per American Heart Association/American College of Cardiology guidelines, ASD with elevated pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) >2/3rd systemic is considered as a contraindication for closure. METHODS Patients with anatomically large ASD measuring >25 mm and a high probability of reversible pulmonary vascular disease were subjected to fenestrated device closure, despite severe PHT and elevated PVR. They were discharged on pulmonary vasodilators and were followed for 39.5 ± 8.5 months. Four patients had repeat cardiac catheterization. RESULTS Six patients underwent successful device closure of large ASD with severe PHT. Their basal Qp:Qs was 2.8 ± 0.3:1 while the systolic PAP and the PVR index (PVRI) were 102.6 ± 11.5 mm Hg and 9.6 ± 1.6 Wu m2 , respectively. Post 100% oxygen inhalation, the Qp:Qs increased to 3.5 ± 0.3:1, systolic PAP remained 103.5 ± 7.6 mm Hg while the PVRI dropped to 5.4 ± 1.1 Wu m2 . The postballoon occlusion systolic PAP decreased to 86.6 ± 8.8 mm Hg. At the last follow-up, their pulmonary artery systolic pressure by tricuspid regurgitation (TR) jet decreased from 105.6 ± 12.6 mm Hg to 45 ± 7.0 mm Hg. During follow-up cardiac catheterization (n = 4), the systolic PAP and PVRI were 55.7 ± 9.2 mm Hg and 3.2 ± 0.4, respectively. CONCLUSIONS Patients with anatomically big defect and a large left to right shunt at baseline with a high probability of reversible PVR benefit with ASD closure and pulmonary vasodilators, despite significantly elevated PAP and PVRI.

Pulmonary hypertension (PH) encompasses a syndrome of diseases that are characterized by elevated pulmonary artery pressure and pulmonary vascular remodeling and that frequently lead to right ventricular (RV) failure and death. Several types of PH exhibit sexually dimorphic features in disease penetrance, presentation, and progression. Most sexually dimorphic features in PH have been described in pulmonary arterial hypertension (PAH), a devastating and progressive pulmonary vasculopathy with a 3-year survival rate

Lymphangioleiomyomatosis (LAM) is a rare diffuse cystic lung disease. Knowledge on LAM-related pulmonary hypertension (PH) is limited. This study aimed to analyze the clinical characteristics of LAM with elevated pulmonary artery pressure (PAP) and evaluate the potential efficacy of sirolimus. The study involved 50 LAM patients who underwent echocardiography. According to the tricuspid regurgitation velocity (TRV), these patients were divided into the TRV ⩽ 2.8 m/s group and TRV > 2.8 m/s group. Both groups comprised 25 females with an average age of 38.6 ± 8.1 and 41.5 ± 8.9 years. In the TRV > 2.8 m/s group, the estimated systolic PAP (SPAP) was significantly elevated (52.08 ± 12.45 mmHg vs. 30.24 ± 5.25 mmHg, P < 0.01). Linear analysis showed that SPAP was correlated with forced expiratory volume in 1 s (FEV1), diffusing capacity of the lungs for carbon monoxide, alveolar arterial oxygen gradient (PA-aO2), and 6 min walking distance (r =-0.392, -0.351, 0.450, and -0.591, respectively; P < 0.05), in which PA-aO2 was a risk factor for SPAP elevation (β = 0.064, OR = 1.066, P < 0.05). Moreover, in 10 patients who received sirolimus therapy, SPAP decreased from 57.0 12.6 mmHg to 35.2 ± 11.1 mmHg. The study showed that LAM patients with PH exhibit poor pulmonary function and hypoxemia and may benefit from sirolimus treatment.

Iron and oxygen are essential to aerobic organisms, and their biologic functions are intertwined. For example, iron as a component of hemoglobin is required for oxygen transport to tissues, which is critical for energy generation. However, excess iron in combination with oxygen can generate toxic free radicals that damage cellular components. It is therefore not surprising that iron and oxygen homeostasis are both tightly controlled and closely interwoven (reviewed in refs. 1 and 2). Emerging literature suggests an intriguing link between iron and oxygen in the regulation of pulmonary vascular function. Hypoxia is well described to cause pulmonary vascular constriction as a mechanism to match blood flow with ventilation. Studies have also demonstrated that systemic iron deficiency exaggerates, whereas iron supplementation ameliorates, the pulmonary vasoconstriction response to hypoxia (3⇓–5). Moreover, iron deficiency is highly prevalent in patients with pulmonary arterial hypertension (PAH) (6⇓⇓–9), a heterogeneous disease characterized by elevated pulmonary artery pressure with concomitant elevated pulmonary vascular resistance that can be idiopathic, heritable, or associated with drugs, infections, connective tissue disease, congenital heart disease, or other causes (reviewed in ref. 10). If left untreated, PAH leads to progressive right heart failure and can ultimately be fatal. Iron deficiency in PAH patients is associated with greater disease severity and worsening survival, and intriguingly, iron supplementation has been shown to improve exercise capacity and quality of life in small clinical studies (6, 8, 9, 11, 12). However, it remains unclear how systemic iron deficiency impacts pulmonary vascular function and influences PAH. A study in PNAS by Lakhal-Littleton et al. (13) provides mechanistic insights into local iron regulation in the lung vasculature and how iron deficiency specifically in pulmonary artery smooth muscle cells (PASMCs) may contribute to the pathogenesis of PAH. At … [↵][1]1Email: Babitt.Jodie{at}mgh.harvard.edu. [1]: #xref-corresp-1-1

Pulmonary hypertension is a rare vascular disease that can affect patients with or surviving malignancy resulting in significant morbidity and high mortality. Malignant diseases can lead to elevated pulmonary artery pressure through different mechanisms, either directly by structural obstruction of pulmonary vessels or indirectly through hyperco­agulable state or treatment toxicity culminating in high pulmonary vascular resistance. The most common causes of cancer-related pulmonary hypertension are thromboembolic diseases, tumour emboli and treatment toxicity and less commonly intravascular tumours and malignant extrinsic compression.

Cardiopulmonary exercise testing (CPET) is useful for the evaluation of patients with suspected or confirmed pulmonary hypertension (PH). End-tidal carbon dioxide pressure (PETCO2) during exercise is reduced with elevated pulmonary artery pressure. However, the utility of ventilatory parameters such as CPET for detecting PH remains unclear. We conducted a review in 155 patients who underwent right heart catheterization and CPET. Fifty-nine patients had PH [mean pulmonary arterial pressure (mPAP) ≥25 mmHg]. There was an inverse correlation between PETCO2 at the anaerobic threshold (AT) and mPAP (r = -0.66; P

Background and objective Elevated mean pulmonary artery pressure (mPAP) is a significant prognostic indicator in idiopathic pulmonary fibrosis (IPF). It has been reported that the computed tomography-determined ratio of the diameter of the pulmonary artery to the aorta (PA:A) is correlated with mPAP in various respiratory diseases. However, in patients with IPF, whether the PA:A can be used to predict elevated mPAP and the prognostic value of the PA:A has not been fully evaluated. Methods We conducted a single-centre, observational study of 177 consecutive IPF patients who underwent right heart catheterization. We examined the association between the PA:A and mPAP in these patients, and performed a receiver operating characteristic (ROC) analysis to test the diagnostic accuracy of the PA:A in predicting mPAP > 20 mm Hg (pulmonary hypertension (PH) or borderline PH) in relation to survival. Results In a multivariate linear regression analysis, the PA:A, 6-min walk distance and diffusion capacity for carbon monoxide (DLCO ) % predicted were independent explanatory variables of elevated mPAP (P 0.9 to be optimal for predicting mPAP > 20 mmHg (area under the curve (AUC) = 0.75; 95% CI: 0.65–0.84). Patients with a PA:A > 0.9 also had a worse prognosis (P = 0.009). Conclusion Measurement of the PA:A is a useful and convenient method to predict elevated mPAP in IPF at initial evaluation. Moreover, a PA:A >0.9 was found to be an indicator of worse prognosis.

Exercise pulmonary hypertension (EPH) indicates an abnormally elevated pulmonary artery pressure (PAP) during exercise. The physiological range of PAP during exercise remains poorly defined and, therefore, a universally accepted definition of EPH remains elusive. Nevertheless, previous data concerning the distribution of PAP in normal populations and more recent retrospective clinical data enhanced our ability to define EPH. EPH can impair exercise capacity and cause dyspnea. The underlying pathophysiology of the arterial form of EPH (EPAH) appears to be similar to that seen in resting pulmonary arterial hypertension (PAH), and EPAH individuals are at risk of developing resting PAH. Patients with collagen vascular disease, especially scleroderma, are at risk for EPAH and its presence indicates a relatively poor prognosis. The prevalence of EPAH in scleroderma may be as high as 50%. The utility of pulmonary vasodilator therapy for EPAH is not well defined; however, a sizable subgroup of EPAH patients will achieve an improvement in symptoms.

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are subtypes of pulmonary hypertension—a rare, life-threatening condition defined by chronically elevated pulmonary artery pressure. Treatment goals include improving patient functioning, symptom management, and delaying disease progression. Traditional therapies have focused on affected physiologic pathways, with endothelin-receptor antagonists and/or phosphodiesterase-5 inhibitors as first-line agents and prostacyclins for more severe disease. Riociguat, a therapeutic agent that stimulates soluble guanylate cyclase via nitric-oxide pathways, was approved in 2013 for treatment of PAH and CTEPH. Riociguat significantly improved exercise capacity, hemodynamic parameters, and other functional endpoints in phase 3 trials. Safety and efficacy were maintained in long-term extension studies. Adverse events (AEs) were generally mild to moderate and self-limiting and did not require treatment discontinuation. To optimize adherence, frequent patient monitoring and management of AEs are recommended. Management strategies include patient education, treatment/prevention of adverse events, and individualized dose adjustment. Funding: Bayer HealthCare Pharmaceuticals, Whippany, NJ, USA.

Aim: To investigate the prognostic value of early post-transplant hemodynamic measurements on 5-year mortality in cardiac recipients (HTx). Methods: A right heart catheterization was performed in 290 heart transplantation (HTx) recipients at a one-year post-HTx evaluation. To study the effect of post-HTx hemodynamic variables on 5-year outcome, the cohort was stratified into several subgroups. For right atrial pressure (RAP), mean pulmonary artery pressure (MPAP), pulmonary artery wedge pressure (PAWP), and pulmonary vascular resistance (PVR), patients with values from the upper 10th percentile (high), were compared with those with values from the remaining lower 90th percentile (normal). For cardiac index (CI), patients with values from the lower 10th percentile (low) were compared with those with values from the remaining upper 90th percentile (normal). Results: Death or re-transplantation within 5 years after the one-year control occurred in 44 patients (13%). Of those, death or re-HTx was related to graft failure in 20 of cases (45%) and non-cardiac causes in 24 of cases (55%). The risk of death or re-HTx was higher in the subgroup with MPAP above 23 mmHg than those equal to or below this value [hazard ratio 3.22, 95% confidence interval (CI) 1.49–6.97; P = 0.003]. The association remained significant despite adjustment for several comorbidities. There were no differences in outcome between subgroups stratified with respect to high versus low RAP, PAWP, CI or PVR. Conclusion: Elevated pulmonary artery pressure at a first annual evaluation after HTx was the only hemodynamic variable that predicted impaired outcome in cardiac recipients. Keywords: Heart transplantation, Hemodynamics, Pulmonary arterial hypertension

Management of pediatric pulmonary hypertension associated with congenital heart disease (PHT-CHD) is challenging. Some patients have persistently elevated pulmonary artery pressure (PAP) after cardiac surgery, an undesired condition that is difficult to predict. We investigated the value of clinical, hemodynamic, and histopathological data in predicting the outcome in a prospective cohort. Patients with PHT-CHD received sildenafil orally pre- and postoperatively for six months and then were subjected to a catheter study. Thirty-three patients were enrolled (age range = 4.6–37.0 months). Pulmonary vascular resistance (PVR) was 4.9 (range = 3.9–7.2) Wood units × m 2 (median with IQR). Twenty-two patients had a ≥ 20% decrease in PVR and pulmonary-to-systemic vascular resistance ratio (PVR/SVR) in response to inhaled nitric oxide (NO). The response was directly related to the degree of medial hypertrophy of pulmonary arterioles ( P 25 mmHg and >3.0 U × m 2 , respectively). A preoperative PVR/SVR of ≥24% during NO inhalation and a wall thickness of arteries accompanying respiratory bronchioli of ≥4.7 (Z score) were identified, respectively, as risk and protection factors for abnormal postoperative hemodynamics (hazard ratio [95% CI] = 1.09 [1.01–1.18], P = 0.036; and 0.69 [0.49–0.98], P = 0.040, respectively). Thus, in PHT-CHD patients receiving oral sildenafil pre- and post-surgical repair of cardiac lesions, mid-term postoperative outcome is predictable to some extent.

Pulmonary hypertension is characterized by elevated pulmonary artery pressure caused by several clinical conditions that affect pulmonary vasculature. Morbidity and death in this condition are related to the development of right ventricular failure. Normal physiologic changes that occur in pregnancy to support the growing fetus can pose hemodynamic challenges to the pregnant patient with pulmonary hypertension that results in increased morbidity and mortality rates. Current guidelines recommend that patients with known pulmonary hypertension be counseled against pregnancy. This review aims to provide clinicians with guidelines for preconception counseling, medication management, and delivery planning.

BACKGROUND: Pulmonary hypertension (PH) comprises a group of complex and heterogenous conditions, characterised by elevated pulmonary artery pressure, and which left untreated leads to right‐heart failure and death. PH includes World Health Organisation (WHO) Group 1 pulmonary arterial hypertension (PAH); Group 2 consists of PH due to left‐heart disease (PH‐LHD); Group 3 comprises PH as a result of lung diseases or hypoxia, or both; Group 4 includes PH due to chronic thromboembolic occlusion of pulmonary vasculature (CTEPH), and Group 5 consists of cases of PH due to unclear and/or multifactorial mechanisms including haematological, systemic, or metabolic disorders. Phosphodiesterase type 5 (PDE5) inhibitors increase vasodilation and inhibit proliferation. OBJECTIVES: To determine the efficacy of PDE5 inhibitors for pulmonary hypertension in adults and children. SEARCH METHODS: We performed searches of CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science up to 26 September 2018. We handsearched review articles, clinical trial registries, and reference lists of retrieved articles. SELECTION CRITERIA: We included randomised controlled trials that compared any PDE5 inhibitor versus placebo, or any other PAH disease‐specific therapies, for at least 12 weeks. We include separate analyses for each PH group. DATA COLLECTION AND ANALYSIS: We imported studies identified by the search into a reference manager database. We retrieved the full‐text versions of relevant studies, and two review authors independently extracted data. Primary outcomes were: change in WHO functional class, six‐minute walk distance (6MWD), and mortality. Secondary outcomes were haemodynamic parameters, quality of life/health status, dyspnoea, clinical worsening (hospitalisation/intervention), and adverse events. When appropriate, we performed meta‐analyses and subgroup analyses by severity of lung function, connective tissue disease diagnosis, and radiological pattern of fibrosis. We assessed the evidence using the GRADE approach and created 'Summary of findings' tables. MAIN RESULTS: We included 36 studies with 2999 participants (with pulmonary hypertension from all causes) in the final review. Trials were conducted for 14 weeks on average, with some as long as 12 months. Two trials specifically included children. Nineteen trials included group 1 PAH participants. PAH participants treated with PDE5 inhibitors were more likely to improve their WHO functional class (odds ratio (OR) 8.59, 95% confidence interval (CI) 3.95 to 18.72; 4 trials, 282 participants), to walk 48 metres further in 6MWD (95% CI 40 to 56; 8 trials, 880 participants), and were 22% less likely to die over a mean duration of 14 weeks (95% CI 0.07 to 0.68; 8 trials, 1119 participants) compared to placebo (high‐certainty evidence). The number needed to treat to prevent one additional death was 32 participants. There was an increased risk of adverse events with PDE5 inhibitors, especially headache (OR 1.97, 95% CI 1.33 to 2.92; 5 trials, 848 participants), gastrointestinal upset (OR 1.63, 95% CI 1.07 to 2.48; 5 trials, 848 participants), flushing (OR 4.12, 95% CI 1.83 to 9.26; 3 trials, 748 participants), and muscle aches and joint pains (OR 2.52, 95% CI 1.59 to 3.99; 4 trials, 792 participants). Data comparing PDE5 inhibitors to placebo whilst on other PAH‐specific therapy were limited by the small number of included trials. Those PAH participants on PDE5 inhibitors plus combination therapy walked 19.66 metres further in six minutes (95% CI 9 to 30; 4 trials, 509 participants) compared to placebo (moderate‐certainty evidence). There were limited trials comparing PDE5 inhibitors directly with other PAH‐specific therapy (endothelin receptor antagonists (ERAs)). Those on PDE5 inhibitors walked 49 metres further than on ERAs (95% CI 4 to 95; 2 trials, 36 participants) (low‐certainty evidence). There was no evidence of a difference in WHO functional class or mortality across both treatments. Five trials compared PDE5 inhibitors to placebo in PH secondary to left‐heart disease (PH‐LHD). The quality of data were low due to imprecision and inconsistency across trials. In those with PH‐LHD there were reduced odds of an improvement in WHO functional class using PDE5 inhibitors compared to placebo (OR 0.53, 95% CI 0.32 to 0.87; 3 trials, 285 participants), and those using PDE5 inhibitors walked 34 metres further compared to placebo (95% CI 23 to 46; 3 trials, 284 participants). There was no evidence of a difference in mortality. Five trials compared PDE5 inhibitors to placebo in PH secondary to lung disease/hypoxia, mostly in COPD. Data were of low quality due to imprecision of effect and inconsistency across trials. There was a small improvement of 27 metres in 6MWD using PDE5 inhibitors compared to placebo in those with PH due to lung disease. There was no evidence of worsening hypoxia using PDE5 inhibitors, although data were limited. Three studies compared PDE5 inhibitors to placebo or other PAH‐specific therapy in chronic thromboembolic disease. There was no significant difference in any outcomes. Data quality was low due to imprecision of effect and heterogeneity across trials. AUTHORS' CONCLUSIONS: PDE5 inhibitors appear to have clear beneficial effects in group 1 PAH. Sildenafil, tadalafil and vardenafil are all efficacious in this clinical setting, and clinicians should consider the side‐effect profile for each individual when choosing which PDE5 inhibitor to prescribe. While there appears to be some benefit for the use of PDE5 inhibitors in PH‐left‐heart disease, it is not clear based on the mostly small, short‐term studies, which type of left‐heart disease stands to benefit. These data suggest possible harm in valvular heart disease. There is no clear benefit for PDE5 inhibitors in pulmonary hypertension secondary to lung disease or chronic thromboembolic disease. Further research is required into the mechanisms of pulmonary hypertension secondary to left‐heart disease, and cautious consideration of which subset of these patients may benefit from PDE5 inhibitors. Future trials in PH‐LHD should be sufficiently powered, with long‐term follow‐up, and should include invasive haemodynamic data, WHO functional class, six‐minute walk distance, and clinical worsening.

Author(s): Nguyen, Quyen L; Wang, Yinna; Helbling, Nicole; Simon, Marc A; Shiva, Sruti | Abstract: BackgroundPulmonary hypertension (PH) is characterized by elevated pulmonary artery pressure but classified into subgroups based on disease etiology. It is established that systemic bioenergetic dysfunction contributes to the pathogenesis of pulmonary arterial hypertension classified as World Health Organization (WHO) Group 1. Consistent with this, we previously showed that platelets from Group 1 PH patients demonstrate increased glycolysis and enhanced maximal capacity for oxidative phosphorylation, which is due to increased fatty acid oxidation (FAO). However, it remains unclear whether identical mitochondrial alterations contribute to the pathology of other PH subgroups. The most prevalent subgroup of PH is WHO Group 2, which encompasses pulmonary venous hypertension secondary to left heart disease. Here, we hypothesized that platelets from Group 2 subjects show bioenergetic alteration compared to controls, and that these changes were similar to Group 1 PH patients.Method and resultsWe isolated platelets from subjects with Group 2 PH and controls (n = 20) and measured platelet bioenergetics as well as hemodynamic parameters. We demonstrate that Group 2 PH platelets do not show a change in glycolytic rate but do demonstrate enhanced maximal capacity of respiration due at least partially to increased FAO. Moreover, this enhanced maximal capacity correlates negatively with right ventricular stroke work index and is not changed by administration of inhaled nitrite, a modulator of pulmonary hemodynamics.ConclusionsThese data demonstrate that Group 2 PH subjects have altered bioenergetic function though this alteration is not identical to that of Group 1 PH. The implications of this alteration for disease pathogenesis will be discussed.