Risk Of Pulmonary Hypertension Research Articles

Small for gestational age offspring of short stature mothers and the risk of respiratory morbidity

Small for gestational age (SGA) definition does not distinguish SGA infants who are constitutionally small from small infants with intrauterine growth restriction. It remains challenging to determine whether a neonate is constitutionally small, but this diagnosis is more likely when one or both parents are also small and after excluding other reasons. SGA newborns are at increased risk for pulmonary hypertension and hypoxia. We aimed to study the association between SGA infants born to short-stature mothers (assuming constitutional) and long-term respiratory related morbidity compared to SGA infants born to non-short mothers.

Sedation Prior to Intubation at Birth in Infants with Congenital Diaphragmatic Hernia: An International Survey on Current Practices

Introduction: Infants with congenital diaphragmatic hernia (CDH) are commonly intubated immediately after birth. Consensus on whether to provide sedation prior to intubation in the delivery room is lacking, although avoidance of stress is especially important in this population with high risk of pulmonary hypertension. We aimed at obtaining an overview of local pharmacological interventions and at providing guidance on delivery room management. Methods: An electronic survey was sent to international clinicians in referral centres for prenatal and postnatally diagnosed infants with CDH. This survey addressed demographic information, use of sedation and/or muscle relaxant prior to intubation, and use of pain scales in the delivery room. Results: We received 93 relevant responses from 59 centres. Most centres were from Europe (n = 33, 56%), followed by North America (n = 16, 27%), Asia (n = 6, 10%), Australia (n = 2, 3%), and South America (n = 2, 3%). A total of 19% (11/59) of the centres routinely provided sedation prior to intubation in the delivery room, with midazolam and fentanyl being most often used. Methods of administration varied for all medications provided. Only 5 of 11 centres using sedation reported an adequate sedative effect prior to intubation. Muscle relaxants prior to intubation were used in 12% (7/59) of the centres, although not always in combination with sedation. Conclusion: This international survey shows a substantial variation in sedation practices in the delivery room and scarce use of both sedative agents and muscle relaxants prior to intubation of CDH infants. We provide guidance on developing protocols for pre-intubation medication in this population.

Clinical Presentation and Outcome of Management of Congenital Heart Diseases Associated with Down Syndrome in a Tertiary Care Hospital

Introduction: Treatment of children with Down syndrome having congenital heart defects has not been reported well in Bangladesh. This study has been carried out to inform practitioners about findings from cases in Combined Military Hospital, Dhaka. Methods: Three years retrospective observational study (clinical data, hospital course and follow-up) was carried out on 114 patients (49 males and 65 females, age range 1 month to 12 years) who underwent diagnostic and therapeutic work up in the pediatric cardiology department CMH Dhaka between January 2018 and December 2020. Results: Among 114 patients ,64 were (57%) were infants and 50 were older children (43%) , twenty-five had congestive cardiac failure and eighteen had hypothyroidism. The study showed that 33.3% were atrioventricular septal defect (AVSD), 28.1% were patent ductus arteriosus (PDA),8.75% were tetralogy of Fallot (TOF) ,5.25% were coartation of aorta (COA) ,3.5% were patent ductus arteriosus with coarctation of aorta 3.5%, double outlet right ventricle with pulmonary stenosis were 3.5%, ventricular septal defect were 7% whereas atrial septal defect along with ventricular septal defect were 5.3% ,atrial septal defect were 3.5%, transposition of great arteries with multiple ventricular septal defect were 1.8%.Forty (35%) patients using per cutaneous intervention,had 100% procedural success and no mortality .45 patients underwent surgery,few of them were not operated due to severe pulmonary hypertension. Conclusion: Congenital heart disease was more frequent in DS children,having worse prognosis.Children with DS required special attention due to increased risk of pulmonary hypertension. Delayed treatment was an important risk factor for poor prognosis.So early diagnosis is needed in order to provide optimal intervention and surgery ,before occurrence of irreversible PAH. J Bangladesh Coll Phys Surg 2023; 41: 7-14

Clinical and hemodynamic phenotype of BMPR2 variation carriers with pulmonary arterial hypertension: A systematic review and a call to action

Background: Carriers of variations in the gene encoding bone morphogenetic protein receptor type 2 (BMPR2∆) are at high risk for severe pulmonary arterial hypertension (PAH+). Aim: To define the clinical and hemodynamic phenotype of BMPR2∆/PAH+ patients. Methods: We performed a systematic review encompassing observational data until July 2019 about BMPR2∆ and confirmed PAH diagnosis. According to international clinical guidelines, we aimed to determine the clinical and hemodynamic phenotype of BMPR2D/PAH+ patients. We also explored functional assessment and risk stratification. PROSPERO ID CRD42019124324. Results: We included 54 reports with 6,668 PAH+ patients, 1,220 were BMPR2∆/PAH+ with an allele frequency within studies ranging from 8.8% to 24.9%. Female sex was predominant, and age at diagnosis ranged from 32.2 to 46.2 years. We observed the occurrence of BMPR2∆ across all PAH clinical classifications, except for schistosomiasis. BMPR2∆ correlated with severity signs and symptoms in PAH, poor functional class, severe pulmonary hypertension with elevated pulmonary vascular resistance, and low cardiac index and output. The clinical and hemodynamic missing data ranged between 28%-49% and 50%-65%, respectively. Conclusion: BMPR2∆/PAH+ patients present a phenotype with high mortality risk. The clinical triad of dyspnea, syncope, and hemoptysis could suggest BMPR2∆/PAH+. However, poor clinical and hemodynamic characterization hinders translating the benefits of genomic analyses to the clinical setting.

346 IMPACT OF EXERCISE-INDUCED PULMONARY HYPERTENSION ON THE RIGHT VENTRICLE AND WORSENING OF CARDIOVASCULAR RISK IN HIV PATIENTS

Abstract Background and Aim Exercise-induced pulmonary hypertension (ExPH), due to impaired pulmonary vascular and right ventricular contractile reserve on effort,predicts clinical outcomes, such as all-cause mortality or cardiovascular (CV) hospitalizations in patients with dyspnea on effort. We investigated its prognostic significance in HIV patients at risk for Pulmonary Arterial Hypertension (PAH). Methods In 52 consecutive HIV patients with either low (n=47) or intermediate probability (n=5) of PH at rest, we evaluated at time 0 and after 2 years the prognostic determinants of CV risk: onset or progression of heart failure/syncope; worsening of functional class; functional performance at the 6-Minute Walking Test and at cardiopulmonary exercise test (CPET); right atrial area; and pericardial effusion. We assigned a severity score 1-3 to each prognostic determinant, derived an overall CV risk score, and its 0-2 years change. Patients were classified as either at low, intermediate or high probability of ExPH at Stress Echocardiography (ESE), while ExPH at CPET was defined as absence of PH at rest, reduced peak VO2, VE/VCO2 >30 at anaerobic threshold, reduced O2 pulse, and ΔVO2/ΔW <9 mL/min/W. We then correlated ExPH at time 0 with clinical worsening (risk score increase >20% after 2 years). Results Right ventricle (RV) systolic function was significantly reduced in patients with ExPH compared to those without ExPH at CPET, as well as in patients with intermediate/high compared to those with low probability of ExPH at ESE, who exhibited worse values of TAPSE and FAC (p<0.001 and p=0.01, respectively). A significant higher proportion of patients with ExPH (CPET) or with intermediate/high probability of ExPH (ESE) had higher sPAP (p<0.001), mPAP (p=0.004), higher TRV (p=0.006) as well as higher right atrial area (p<0.001) and indexed right atrial volume (p=0.004). Total pulmonary vascular resistance (expressed by the ratio between TRV and velocity-time integral at the level of right ventricular outflow tract) was higher in patients with ExPH as well as in patients with intermediate/high probability of ExPH (p<0.001). Patients with intermediate/high probability of ExPH at ESE showed a trend towards clinical worsening compared to those with low probability of ExPH, albeit not statistically significant (p=0.137). In patients with low probability of ExPH, none had >20% increased CV risk score after 2 years. We found an association between higher NT-proBNP and the presence or intermediate/high probability of ExPH after 2 years (p=0.048 at CPET, p=0.033 at ESE). Conclusions At short follow-up, ExPH is associated with a worsening trend in the CV risk score which, if confirmed after longer follow-up, could contribute to better risk stratification in HIV patients.

860 TRICUSPID REGURGITATION RELATED TO CARDIAC IMPLANTABLE DEVICES: A NEW ENTITY?

Abstract Background. The incidence of cardiac implantable electronic device (CIED) implantation is currently growing. Patients who develop a moderate to severe CIED-induced tricuspid regurgitation (TR) are at higher risk of pulmonary hypertension, right heart failure (HR) and have higher mortality. Transthoracic echocardiography (TTE) is the most common method for TR grading, while transesophageal echocardiography (TOE) with three-dimensional (3D) imaging is nowadays gaining importance to reconstruct valve morphology and to determine the TR pathophysiology. Case Summary. We present the case of an 83-year-old man with multiple comorbidities, affected by non-ischemic dilated cardiomyopathy, for which a biventricular defibrillator (ICD-CRT) was implanted in 2007 in primary prevention. Over the years, the patient has been a CRT-responder, with partial recovery of the ejection fraction (40% in 2022 versus 25%). In 2018 he had an episode of acute pulmonary oedema and ventricular fibrillation with ICD intervention; during that hospitalization, the right ventricular catheter (EC) was replaced due to dysfunction. In 2022, the patient presented to our hospital for anasarca due to right HF. TTE and TOE showed new onset of right heart dilation and dysfunction with severe TR, which was predominantly caused from lead impingement of the septal tricuspid valve (TV) leaflet and later from secondary dilation of the TV annulus. The patient responded well to medical therapy and was discharged. Discussion. CIED-related TR is getting more relevant since its growing prevalence and its prognostic impact, even if little is known about why some patients develop moderate-to-severe CIED-related TR. Clinicians should be aware of this entity and follow the patients with TR over the time with periodic echocardiograms. TOE and 3D imaging should always be performed to understand the mechanism of the TR and to select the optimal treatment. Currently, no guidelines nor randomized data are available in order to guide treatment in these patients. Figure 1:4-chamber views with and without color Doppler showing the ventricular EC passing the TV through with the presence of peri-catheter TR.Figure 2:trans-gastric TOE xPlane views showing how the ventricular EC determines a restrictive movement of the septal TV leaflet, causing the severe TR to form.

Interest of TAPSE/sPAP ratio for noninvasive pulmonary arterial hypertension risk assessment.

Although ventriculoarterial coupling is associated with better survival in pulmonary arterial hypertension (PAH), existing PAH risk assessment method has not considered echocardiographic criteria of right ventricular to pulmonary artery coupling. We aimed to test the prognostic value of the echocardiographic tricuspid annular plane systolic excursion/systolic pulmonary artery pressure (TAPSE/sPAP) ratio for noninvasive PAH risk assessment. We retrospectively studied a cohort of 659 incident PAH patients from 4 independent French PH centers (training cohort: n=306, validation cohort n=353) who underwent follow-up TAPSE/sPAP measurement in addition to previously validated noninvasive risk stratification variables. The primary composite outcome was 3-year all-cause mortality or lung transplantation from re-evaluation. Mean age was 55 ± 17 years-old with a majority of female (66%). The three main PAH causes were connective tissue disease (26%), idiopathic (24%) and porto-pulmonary (19%). The primary composite outcome occurred in 71 (23%) patients. Multivariable Cox regression analysis retained 3 noninvasive low-risk criteria as associated with the primary composite outcome: NYHA I-II (p=0.001), NTproBNP <300 ng/L or BNP <50 ng/L (p=0.004), and TAPSE/sPAP >0.33 mm/mmHg (p=0.004). The more the low-risk criteria achieved at follow-up, the better the event-free survival both in the training and validation cohort (log-rank p < 0.001). In the training cohort, the c-index for these 3 criteria, for COMPERA 2.0 and for the noninvasive French Pulmonary Hypertension Network method were 0.75, 95%CI(0.70-0.82), 0.72 95%CI(0.66-0.75), 0.71 95%CI(0.62-0.73), respectively. The 3 following dichotomized low-risk criteria: TAPSE/sPAP >0.33 mm/mmHg, NYHA I-II and NTproBNP <300 ng/L or BNP <50 ng/L allow to identify low-risk PAH patients at follow-up.

CSL112 Increases Plasma Cholesterol Efflux Capacity and Reduces Erythrocyte Membrane Cholesterol Content in Blood Samples from Patients with Sickle Cell Disease

Background: Lipid homeostasis is abnormal in sickle cell disease (SCD) and contributes to elevated erythrocyte cholesterol content which has been implicated in sickling. The highly oxidative environment in blood from patients with SCD alters high-density lipoprotein (HDL) composition and impairs HDL particle remodeling. Specifically, it negatively impacts on the capacity of HDL particles to mediate apolipoprotein A-I (apoA-I) exchange and protect against inflammation. Low apoA-I levels and altered composition of HDL have been well-documented at steady state, associated with high risk features of SCD, including endothelial dysfunction and risk of pulmonary hypertension. The low levels and activity of apoA-I fall even further during vaso-occlusive events in SCD. This diminished pool of apoA-I activity may mediate reduced capacity of HDL to extract cholesterol from erythrocyte membranes and increase risk of vascular dysfunction. Purpose: In this study we aimed to determine whether plasma derived apoA-I (CSL112; apolipoprotein A-I (human)) could elevate the cholesterol efflux capacity (CEC) of plasma from SCD patients and thereby reduce erythrocyte membrane cholesterol content. Methods: All SCD subjects (n=14) had confirmed HbSS genotype except one who was with HbS/β0-thalassemia, healthy control subjects (n=13) were not race-matched. CSL112 was incubated with fresh blood derived from control subjects and SCD patients for 6 hours at 37°C. The cholesterol content of ghost membranes of isolated erythrocytes was measured. HDL particle size distribution was assessed by native gel electrophoresis followed by western blotting. The ex vivo capacity of apoB-depleted plasma to efflux cholesterol was determined using [3H]cholesterol-loaded RAW264.7 macrophages. Results: CEC of SCD plasma was attenuated (75.9 ± 7.4%, n=14) compared to controls (100%, n=13), with a predominant decrease of ATP binding cassette transporter A1 (ABCA1)-dependent CEC (77.7 ± 9.2% vs 100%, respectively). Consistently, SCD plasma showed a trend towards lower levels of pre-β1 HDL (78.5 ± 6.5%) as compared to controls (100 %). Incubation with CSL112 raised plasma levels of small HDL species and pre-β1 HDL, resulting in a more than 3.5 fold increase of CEC in both patients and controls. Treatment of SCD blood with CSL112 reduced erythrocyte cholesterol content to a greater extent compared to control blood (% reduction: 12.8% ± 3.1% in SCD, 6.3% ± 5.4% in controls). Conclusion: Our data suggest that reduced levels of lipid-poor pre-β1 HDL in SCD plasma reflect impaired HDL particle remodeling and account for a decreased CEC. CSL112 may acutely generate HDL species which optimally support ABCA1-dependent cholesterol efflux and thereby improve HDL function, normalize erythrocyte membrane cholesterol content and correct the imbalance in cellular cholesterol homeostasis in SCD patients. ApoA-I as a potential therapeutic could have implications in the pathobiologic understanding and future clinical management of vaso-occlusive crisis and of chronic vascualopathy such as pulmonary hypertension.

Abstract 13527: The Development of a Remote Pulmonary Arterial Hypertension Risk Score Utilising Remote Monitoring Technology to Monitor Parameters Associated With Mortality in Pulmonary Arterial Hypertension

Background: In patients with pulmonary arterial hypertension (PAH) risk stratification is used to aid clinical decision making and guide treatment categorising patients as low (&lt;5%), intermediate (5-10%), or high mortality risk (&gt;10%) at 1 year based on hospital investigations. Risk stratification based on remote parameters may facilitate early evaluation of clinical efficacy following treatment change or indicate clinical stability/deterioration, thereby permitting early intervention. Methods: Patients with PH were identified from the ASPIRE (6/YH/0352) database 2/2001-6/2019. Random allocation was used to form a derivation (n=3832). Univariate Cox Regression and stepwise forward multivariate analysis were undertaken in the derivation cohort to identify parameters that may be remote monitored that were associated with mortality. Mortality weighted z-scores of age, incremental shuttle walk test (ISWT), heart rate (HR) and total pulmonary resistance (TPR) were summed to give an individual remote risk score value. LOESS regression was used to determine 1 year risk thresholds applied to a PAH validation cohort (n=590). Results: Multivariate analysis of the derivation cohort demonstrated that ISWT, HR and TPR had statistically significant relationships to mortality. Survival analysis showed increased mortality with each decile of baseline risk score with the 10 th decile at increased risk of mortality compared the 1 st decile (OR 5.5, 95%CI 4.3-7.0, each decile p&lt;0.01, Figure). In patients with PAH, LOESS derived thresholds identified patients at low, intermediate and high risk with 1 year mortalities of 4.6, 9.8 and 15.1% respectively (low-int OR 1.9, low-high OR 2.7,p&lt;0.01,Figure). Conclusion: A score of remote monitored parameters, when applied at diagnosis, accurately categorised patients as low, intermediate, or high risk. This system may be applied to remote monitored physiological data to provide real time risk stratification.

Pulmonary Hypertension in Preterm Infants Treated With Laser vs Anti–Vascular Endothelial Growth Factor Therapy for Retinopathy of Prematurity

Anti-vascular endothelial growth factor (VEGF) therapy for retinopathy of prematurity (ROP) has potential ocular and systemic advantages compared with laser, but we believe the systemic risks of anti-VEGF therapy in preterm infants are poorly quantified. To determine whether there was an association with increased risk of pulmonary hypertension (PH) in preterm infants with ROP following treatment with anti-VEGF therapy as compared with laser treatment. This multicenter retrospective cohort study took place at neonatal intensive care units of 48 children's hospitals in the US in the Pediatric Health Information System database from 2010 to 2020. Participants included preterm infants with gestational age at birth 22 0/7 to 31 6/7 weeks who had ROP treated with anti-VEGF therapy or laser photocoagulation. Anti-VEGF therapy vs laser photocoagulation. New receipt of pulmonary vasodilators at least 7 days after ROP therapy was compared between exposure groups, matched using propensity scores generated from preexposure variables, and adjusted for birth year and hospital. The odds of receiving an echocardiogram after 30 days of age was also included to adjust for secular trends and interhospital variation in PH screening. Among 1577 patients (55.9% male) meeting inclusion criteria, 689 received laser photocoagulation and 888 received anti-VEGF treatment (95% bevacizumab, 5% ranibizumab). Patients were first treated for ROP at median 36.4 weeks' postmenstrual age (IQR, 34.6-38.7). A total of 982 patients (491 in each group) were propensity score matched. Good covariate balance was achieved, as indicated by a model variance ratio of 1.15. More infants who received anti-VEGF therapy were treated for PH, but when adjusted for hospital and year, this was no longer statistically significant (6.7%; 95% CI, 2.6-6.9 vs 4.3% 95% CI, 4.4-10.2; adjusted odds ratio, 1.62; 95% CI, 0.90-2.89; P = .10). Anti-VEGF therapy was not associated with greater use of pulmonary vasodilators after adjustment for hospital and year. Our findings suggest exposure to anti-VEGF may be associated with PH, although we cannot exclude the possibility of residual confounding based on systemic comorbidities or hospital variation in practice. Future studies investigating this possible adverse effect seem warranted.

COMPARISON BETWEEN PULMONARY ARTERIAL HYPERTENSION (PAH) RISK ASSESSMENT METHODS, INCLUDING PULMONARY HYPERTENSION OUTCOME RISKS ASSESSMENT (PHORA)

COMPARISON BETWEEN PULMONARY ARTERIAL HYPERTENSION (PAH) RISK ASSESSMENT METHODS, INCLUDING PULMONARY HYPERTENSION OUTCOME RISKS ASSESSMENT (PHORA)

Analysis of family histories suggests shared genetic risk for chronic thromboembolic pulmonary hypertension and venous thromboembolism

Chronic thromboembolic pulmonary hypertension (CTEPH) and acute pulmonary embolism (PE) are related phenotypes, however, previous reports have suggested that genetic risk factors for CTEPH and PE differ. Here we report that a family history of VTE is equally frequent in individuals with CTEPH and PE, suggesting that shared genetic variants may influence risk of both phenotypes. We also provide the first estimate of the frequency of familial CTEPH, which we identified in 2.2% of CTEPH patients in our cohort.

Early-term outcomes of the pulmonary embolism response team.

Treatment of pulmonary embolism varies according to the different clinical presentations. Pulmonary embolism response teams (PERT) might improve outcomes of pulmonary embolism with faster evaluation and increased usage of advanced treatment methods. In this study, the effects of PERT for the treatment of pulmonary embolism were investigated. In this retrospectively analyzed study, patients diagnosed with PE in our hospital between March 1st, 2019 and February 28th, 2022 were included. Patients' medical records were evaluated according to the treatment procedures and early outcomes. Ninety-eight patients with pulmonary embolism were evaluated by the PERT during the study period. The mean age was 62.8+16.4 years and 59% were male. All patients with intermediate-low risk were treated medically. About 59.2% of the patients were hospitalized. The rate of catheter-directed thrombolysis was 37.8% (n=37). Systemic thrombolytic therapy was performed on two patients. One patient with a metastatic brain tumor was treated with low-molecular-weight heparin. Catheter-directed procedures were performed in 37 patients. The time from diagnosis to reperfusion was 243 minutes. There was one pericardial effusion and one mortality. In the 30-day follow- up there was no re-hospitalization and mortality. PERT might help early triage and treatment of patients with pulmonary embolism. Experienced specialists in this team might contribute to clinical recovery by performing advanced treatment methods and decreasing the risk of chronic thromboembolic pulmonary hypertension in the long term.

Risk stratification in patients with pulmonary arterial hypertension at the time of listing for lung transplantation.

It is unknown whether pulmonary arterial hypertension (PAH) risk stratification instruments could be helpful to support the decision to list a patient for lung transplantation (LT). Our aim was to evaluate contemporary risk assessment tools in a cohort of PAH patients listed for LT. Consecutive PAH patients (without pulmonary veno-occlusive disease or unrepaired congenital heart disease) listed for LT at the French Pulmonary Hypertension Reference Center between January 2006 and December 2018 were included. At the time of listing, risk stratification was assessed using the ESC/ERS criteria, the REVEAL Lite 2 score and the COMPERA 2.0 method. The primary end point was overall survival after LT listing. Secondary outcome measures were mortality on waiting list and posttransplant survival. One hundred and two patients were enrolled (mean age 38 ± 13 years, 69% females). Overall survival after listing was 72%, 58% and 46% at 1, 3 and 5 years respectively. Survival after LT listing was lower in "high-risk" patients according to the ESC/ERS criteria (p=0.0001) and the REVEAL Lite 2 score (p=0.04). The COMPERA 2.0 method discriminated post-listing survival of patients at high-risk, intermediate-high and intermediate-low risk (p=0.04). The proportion of patients requiring urgent transplantation and extracorporeal life support as a bridge to transplantation was higher in the "high-risk" patients. Posttransplant survival was significantly lower in "high-risk" patients according to the ESC/ERS criteria (p=0.0004). High-risk PAH patients at the time of LT listing have poor outcomes, suggesting that LT should be considered earlier in the course of PAH remaining refractory to triple combination therapy with a parenteral prostacyclin.

Validation of the new paediatric pulmonary hypertension risk score by CMR and speckle tracking echocardiography.

In 2019, the European Paediatric Pulmonary Vascular Disease Network (EPPVDN) developed a PH risk score to assess the risk and severity of pulmonary hypertension (PH) in children and young adults. We conducted a prospective observational study to validate the EPPVDN paediatric PH risk score by means of cardiac magnetic resonance imaging (CMR) and echocardiography. During the same inpatient stay, the invasive and noninvasive EPPVDN PH risk scores were determined, and a protocol-driven CMR study was performed on 20 PAH children. Subsequently, we correlated the risk scores with imaging variables derived from CMR and echocardiography, including strain. Further, we applied the risk score to nine children with PAH who received add-on selexipag therapy. Before and approximately sixmonths after selexipag start, the risk score and echocardiographic RV strain were determined and delta changes of both were correlated. We found strong correlations of conventional CMR (r=0.69-0.88), CMR strain (r=0.71-0.88), advanced echocardiographic (r=0.65-0.88) and echocardiographic strain variables (r=0.67-0.86) with the EPPVDN PH risk scores (p < .006). In the selexipag cohort, the change in echo-derived RV free wall strain correlated well with the change in the invasive higher risk score (r=0.72, p=.028). We demonstrate strong correlations of outcome-relevant CMR and echocardiographic variables with the EPPVDN PH risk scores, and thus validated the score via independent methods. To achieve broad and easy access, we developed a calculator for the risk score as a web application (www.pvdnetwork.org/pedphriskscore). The novel EPPVDN PH risk score will be useful in routine clinical care and can now be applied in larger paediatric PH studies.

Role of extracorporeal membrane oxygenation and surgical embolectomy in acute pulmonary embolism.

Purpose of reviewSurgery is an important option to consider in patients with massive and submassive pulmonary emboli. Earlier intervention, better patient selection, improved surgical techniques and the use of veno-arterial extracorporeal membrane oxygenation (VA ECMO) have contributed to improve the safety of surgery for pulmonary emboli.Recent findingsVA ECMO is rapidly changing the initial management of patients with massive pulmonary emboli, providing an opportunity for stabilization and optimization before intervention. The early and long-term consequences of acute pulmonary emboli are better understood, in particular with regard to the risks of chronic thromboembolic pulmonary hypertension (CTEPH), an entity that should be identified in the acute setting as much as possible. The presence of chronic thromboembolic pulmonary disease can be associated with persistent haemodynamic instability despite removal of the acute thrombi, particularly if pulmonary hypertension is established. The pulmonary embolism response team (PERT) is an important component in the management of massive and submassive acute pulmonary emboli to determine the best treatment options for each patient depending on their clinical presentation.SummaryThree types of surgery can be performed for pulmonary emboli depending on the extent and degree of organization of the thrombi (pulmonary embolectomy, pulmonary thrombo-embolectomy and pulmonary thrombo-endarterectomy). Other treatment options in the context of acute pulmonary emboli include thrombolysis and catheter-directed embolectomy. Future research should determine how best to integrate VA ECMO as a bridging strategy to recovery or intervention in the treatment algorithm of patients with acute massive pulmonary emboli.

Mixed venous oxygen tension is a crucial prognostic factor in pulmonary hypertension: a retrospective cohort study

BackgroundThe prognostic value of mixed venous oxygen tension (PvO2) at pulmonary hypertension diagnosis treated with selective pulmonary vasodilators remains unclear. This study sought to investigate the association of PvO2 with long-term prognosis in pulmonary arterial hypertension (PAH) and medically treated chronic thromboembolic pulmonary hypertension (CTEPH) and to identify the distinct mechanisms influencing tissue hypoxia in patients with CTEPH or PAH.MethodsWe retrospectively analyzed data from 138 (age: 50.2 ± 16.6 years, 81.9% women) and 268 (age: 57.4 ± 13.1 years, 72.8% women) patients with PAH and CTEPH, respectively, diagnosed at our institution from 1983 to 2018. We analyzed the survival rates of patients with/without tissue hypoxia (PvO2 < 35 mmHg) and identified their prognostic factors based on the pulmonary hypertension risk stratification guidelines.ResultsSurvival was significantly poorer in patients with tissue hypoxia than in those without it for PAH (P = 0.001) and CTEPH (P = 0.017) treated with selective pulmonary vasodilators. In patients with PAH, PvO2 more strongly correlated with prognosis than other hemodynamic prognostic factors regardless of selective pulmonary vasodilators usage. PvO2 was the only significant prognostic factor in patients with CTEPH treated with pulmonary hypertension medication. Patients with CTEPH experiencing tissue hypoxia exhibited significantly poorer survival than those in the intervention group (P < 0.001). PvO2 more strongly correlated with the cardiac index (CI) than the alveolar-arterial oxygen gradient (A-aDO2) in PAH; whereas in CTEPH, PvO2 was more strongly correlated with A-aDO2 than with CI.ConclusionsPvO2 may represent a crucial prognostic factor for pulmonary hypertension. The prognostic impact of tissue hypoxia affects different aspects of PAH and CTEPH, thereby reflecting their distinct pathogenesis.

The effects of glutamine supplementation on markers of apoptosis and autophagy in sickle cell disease peripheral blood mononuclear cells

ObjectivesL-Glutamine was FDA-approved for sickle cell disease (SCD) in 2017, yet the mechanism(s)-of-action are poorly understood. This study investigates the potential activation of autophagy as a previously unexplored mechanism-of-benefit. DesignProspective, open-label, 8-week, phase-2 trial of oral L-glutamine (10 g TID) in patients with SCD at risk for pulmonary hypertension identified by Doppler-echocardiography by an elevated tricuspid-regurgitant-jet-velocity (TRV)≥ 2.5 m/s. Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples taken from SCD patients at baseline, two, four, six and eight weeks of glutamine therapy, and from controls at baseline; BAX (pro-apoptotic marker) and LC3-II/LC3-I (autophagy marker) were measured via western blot analysis to assess apoptosis and autophagy respectively. SettingComprehensive SCD Center in Oakland, California. ResultsPatients with SCD (n = 8) had a mean age of 44 ± 16, 50% were male; 63% Hb-SS, and mean TRV= 3.1 ± 0.7 m/s. Controls’ mean age (n = 5) was 32 ± 12% and 57% were male; all were Hb-AA with a mean TRV= 1.8 ± 0.6. At baseline, SCD-PBMCs had 2-times higher levels of BAX and LC3-I versus controls (both p = 0.03). Levels of BAX expression increased by 300% after 8-weeks of glutamine supplementation (p = 0.005); LC3-I protein levels decreased while LC3-II levels increased by 70%, giving a significant increase in the LC3-II/LC3-I ratio (p = 0.02). ConclusionPBMCs from glutamine-supplemented SCD patients have upregulated apoptotic and autophagy proteins. The parallel increase in BAX and the LC3-II / LC3-I ratio with glutamine supplementation suggest a possible role of autophagic cell death. The increase in apoptotic markers provide insight into a possible mechanism used by peripheral PBMCs during glutamine supplementation in patients with SCD.

Elucidating the Clinical Implications and Pathophysiology of Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction: A Call to Action: A Science Advisory From the American Heart Association.

This science advisory focuses on the need to better understand the epidemiology, pathophysiology, and treatment of pulmonary hypertension in patients with heart failure with preserved ejection fraction. This clinical phenotype is important because it is common, is strongly associated with adverse outcomes, and lacks evidence-based therapies. Our goal is to clarify key knowledge gaps in pulmonary hypertension attributable to heart failure with preserved ejection fraction and to suggest specific, actionable scientific directions for addressing such gaps. Areas in need of additional investigation include refined disease definitions and interpretation of hemodynamics, as well as greater insights into noncardiac contributors to pulmonary hypertension risk, optimized animal models, and further molecular studies in patients with combined precapillary and postcapillary pulmonary hypertension. We highlight translational approaches that may provide important biological insight into pathophysiology and reveal new therapeutic targets. Last, we discuss the current and future landscape of potential therapies for patients with heart failure with preserved ejection fraction and pulmonary vascular dysfunction, including considerations of precision medicine, novel trial design, and device-based therapies, among other considerations. This science advisory provides a synthesis of important knowledge gaps, culminating in a collection of specific research priorities that we argue warrant investment from the scientific community.

The Treatment Strategy for the Atrial Septal Defect in the Presence of Severe Pulmonary Hypertension

Atrial septal defect is one of the most common congenital heart diseases in adults. The defect often leads to volume overload in the right heart coupled with the potential risk of right heart failure and pulmonary arterial hypertension. These conditions lead to worsening in quality of life, decrease in physical capacity, and even to fatal outcomes. The main strategy for treatment of atrial septal defect is a transcatheter or surgical closure of the defect, but in patients with severe pulmonary arterial hypertension, it is recommended to manage pulmonary arterial hypertension and after that treat the defect invasively. This strategy is called “treat and repair” strategy. We present an illustrative case report of management and treatment of atrial septal defect, complicated with severe pulmonary arterial hypertension. In this case, surgical closure of the defect was contraindicated because of the high pulmonary vascular resistance. Therefore, the “treat and repair” strategy was approached. After specific medical treatment of pulmonary arterial hypertension, surgical closure of the defect was chosen and proven successful.