Pulmonary hypertension is a term used to describe a complex multifactorial group of conditions diagnosed by an elevated mean pulmonary artery pressure of 20 mm Hg or higher on right heart catheterization. The diagnosis of pulmonary hypertension in pregnancy is important, as it is associated with high rates of maternal morbidity and mortality, even with modern management. Diagnostic testing is important for establishing the diagnosis, type, and severity of pulmonary hypertension, which in turn, dictates treatment options. Echocardiographic assessment is the first step in diagnosis and the gold standard for monitoring right heart function in patients with pulmonary hypertension. Supportive therapy for pulmonary hypertension includes monitored exercise, vaccination, and avoidance of certain activities. Therapies for pulmonary hypertension are considered conventional or targeted. Conventional therapy includes preventative care, anticoagulation, and calcium channel blockers for appropriate patients. Targeted therapy is usually reserved for patients with World Health Organization group 1 pulmonary arterial hypertension (including idiopathic, heritable, drug-induced or associated with congenital heart disease) and involves different types of direct pulmonary vasodilators. Right heart failure is the end result of pulmonary hypertension and the options for management include medical optimization, support with extracorporeal membrane oxygenation, and combined heart-lung transplantation. With pregnancy, management must be individualized, and patients should be cared for as part of an experienced multidisciplinary team. There are few studies addressing, timing and mode of delivery, including anesthetic considerations. In this review, the natural history of pulmonary hypertension in pregnancy and outcomes are summarized and current evidence-based management is discussed.

Despite advanced therapies, maternal mortality in women with pulmonary arterial hypertension (PAH) remains high in pregnancy and is especially high during the post-partum period. However, recent data indicates that morbidity and mortality during pregnancy and after birth have improved for PAH patients. The current European Society of Cardiology/European Respiratory Society guidelines recommend that women with PAH should not become pregnant. Therefore, the risks associated with pregnancy must be emphasised and counselling offered to women at the time of PAH diagnosis and to women with PAH who become pregnant. Early termination should be discussed. Women who choose to continue with their pregnancy should be treated at specialised pulmonary hypertension centres with experience in managing PAH during and after pregnancy.Copyright ©ERS 2016.

Pulmonary hypertension encompasses a range of conditions directly or indirectly leading to elevated pressures within the pulmonary arteries. Five main groups of pulmonary hypertension are recognized, all defined by a mean pulmonary artery pressure of >20 mmHg: pulmonary arterial hypertension (rare), pulmonary hypertension associated with left-sided heart disease (very common), pulmonary hypertension associated with lung disease (common), pulmonary hypertension associated with pulmonary artery obstructions, usually related to thromboembolic disease (rare), and pulmonary hypertension with unclear and/or multifactorial mechanisms (rare). At least 1% of the world's population is affected, with a greater burden more likely in low-income and middle-income countries. Across all its forms, pulmonary hypertension is associated with adverse vascular remodelling with obstruction, stiffening and vasoconstriction of the pulmonary vasculature. Without proactive management this leads to hypertrophy and ultimately failure of the right ventricle, the main cause of death. In older individuals, dyspnoea is the most common symptom. Stepwise investigation precedes definitive diagnosis with right heart catheterization. Medical and surgical treatments are approved for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. There are emerging treatments for other forms of pulmonary hypertension; but current therapy primarily targets the underlying cause. There are still major gaps in basic, clinical and translational knowledge; thus, further research, with a focus on vulnerable populations, is needed to better characterize, detect and effectively treat all forms of pulmonary hypertension.© 2024. Springer Nature Limited.

Pulmonary arterial hypertension (PAH) is a rare devastating disease characterized by elevated pulmonary artery pressure and increased pulmonary vascular resistance. Females have a higher incidence of PAH, which is reflected globally across registries in the United States, Europe, and Asia. However, despite female predominance, women had better outcomes compared with male patients, a finding that has been labeled the "estrogen paradox." Special considerations should be given to women with PAH regarding sexual health, contraception, family planning, and treatment before, during, and after pregnancy. Pregnant women with PAH should be referred to a pulmonary hypertension care center; a multidisciplinary team approach is recommended, and Cesarean section is the preferred mode of delivery. While pregnancy outcomes have improved over the years with PAH-specific therapy, pregnancy portends a high-risk for those with PAH. Continued research is needed to tailor PAH treatment for women.Copyright: © 2024 The Author(s).

To describe the outcomes of pregnancy in women with pulmonary hypertension.In 2007 the European Registry on Pregnancy and Heart Disease was initiated by the European Society of Cardiology. Consecutive patients with all forms of cardiovascular disease, presenting with pregnancy, were enrolled with the aim of investigating the pregnancy outcomes. This subgroup of the cohort included 151 women with pulmonary hypertension (PH) either diagnosed by right heart catheterization or diagnosed as possible PH by echocardiographic signs, with 26% having pulmonary arterial hypertension (PAH), in three subgroups: idiopathic (iPAH), associated with congenital heart disease (CHD-PAH), or associated with other disease (oPAH), and 74% having PH caused by left heart disease (LHD-PH, n = 112). Maternal mean age was 29.2 ± 5.6 years and 37% were nulliparous. Right ventricular systolic pressure was <50 mmHg in 59.6% of patients, 50-70 mmHg in 28.5% and >70 mmHg in 11.9%. In more than 75% of patients, the diagnosis of PH had been made before pregnancy. Maternal death up to 1 week after delivery occurred in five patients (3.3%), with another two out of 78 patients who presented for follow-up (2.6%), dying within 6 months after delivery. The highest mortality was found in iPAH (3/7, 43%). During pregnancy, heart failure occurred in 27%. Caesarean section was performed in 63.4% (23.9% as emergency). Therapeutic abortion was performed in 4.0%. Complications included miscarriage (5.6%), fetal mortality (2%), premature delivery (21.7%), low birth weight (19.0%), and neonatal mortality (0.7%).Mortality in this group of patients with various forms of PH was lower than previously reported as specialized care during pregnancy and delivery was available. However, maternal and fetal mortality remains prohibitively high in women with iPAH, although this conclusion is restricted by limited numbers. Early advice on contraception, pregnancy risk and fetal outcome remains paramount.© 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

Major advances in pulmonary arterial hypertension, pulmonary hypertension (PH) associated with lung disease, and chronic thromboembolic PH cast new light on the pathogenetic mechanisms, epidemiology, diagnostic approach, and therapeutic armamentarium for pulmonary vascular disease. Here, we summarize key basic, translational, and clinical PH reports, emphasizing findings that build on current state-of-the-art research. This review includes cutting-edge progress in translational pulmonary vascular biology, with a guide to the diagnosis of patients in clinical practice, incorporating recent PH definition revisions that continue emphasis on early detection of disease. PH management is reviewed including an overview of the evolving considerations for the approach to treatment of PH in patients with cardiopulmonary comorbidities, as well as a discussion of the groundbreaking sotatercept data for the treatment of pulmonary arterial hypertension.

Hemodynamic variables such as cardiac index and right atrial pressure have consistently been associated with survival in pulmonary arterial hypertension (PAH) at the time of diagnosis. Recent studies have suggested that pulmonary arterial compliance may also predict prognosis in PAH. The prognostic importance of hemodynamic values achieved after treatment initiation is less well established.Our objective was to evaluate the prognostic importance of clinical and hemodynamic variables during follow-up, including pulmonary arterial compliance, after initial management in PAH. We evaluated incident patients with idiopathic, drug- and toxin-induced, or heritable PAH enrolled in the French pulmonary hypertension registry between 2006 and 2016 who had a follow-up right-sided heart catheterization (RHC). The primary outcome was death or lung transplantation. We used stepwise Cox regression and the Kaplan-Meier method to assess variables obtained at baseline and at first follow-up RHC.Of 981 patients, a primary outcome occurred in 331 patients (33.7%) over a median follow-up duration of 2.8 years (interquartile range, 1.1-4.6 years). In a multivariable model considering only baseline variables, no hemodynamic variables independently predicted prognosis. Median time to first follow-up RHC was 4.6 months (interquartile range, 3.7-7.8 months). At first follow-up RHC (n=763), New York Heart Association functional class, 6-minute walk distance, stroke volume index (SVI), and right atrial pressure were independently associated with death or lung transplantation, adjusted for age, sex, and type of PAH. Pulmonary arterial compliance did not independently predict outcomes at baseline or during follow-up. The adjusted hazard ratio for SVI was 1.28 (95% confidence interval, 1.11-1.49; <0.01) per 10-mL/m decrease and for right atrial pressure was 1.05 (95% confidence interval, 1.02-1.09; <0.01) per 1-mm Hg increase. Among patients who had 2 (n=355) or 3 (n=193) low-risk prognostic features at follow-up, including a cardiac index ≥2.5 L·min·m, 6-minute walk distance >440 m, and New York Heart Association class I or II functional class, lower SVI was still associated with higher rates of death or lung transplantation (<0.01).SVI and right atrial pressure were the hemodynamic variables that were independently associated with death or lung transplantation at first follow-up RHC after initial PAH treatment. These findings suggest that the SVI could be a more appropriate treatment target than cardiac index in PAH.© 2017 American Heart Association, Inc.

Since 2000 there have been major advances in our understanding of the genetic and genomics of pulmonary arterial hypertension (PAH), although there remains much to discover. Based on existing knowledge, around 25–30% of patients diagnosed with idiopathic PAH have an underlying Mendelian genetic cause for their condition and should be classified as heritable PAH (HPAH). Here, we summarise the known genetic and genomic drivers of PAH, the insights these provide into pathobiology, and the opportunities afforded for development of novel therapeutic approaches. In addition, factors determining the incomplete penetrance observed in HPAH are discussed. The currently available approaches to genetic testing and counselling, and the impact of a genetic diagnosis on clinical management of the patient with PAH, are presented. Advances in DNA sequencing technology are rapidly expanding our ability to undertake genomic studies at scale in large cohorts. In the future, such studies will provide a more complete picture of the genetic contribution to PAH and, potentially, a molecular classification of this disease.

Heritable pulmonary arterial hypertension (PAH) is most commonly due to heterozygous mutations of theBMPR2gene. Based on expert consensus, guidelines recommend annual screening echocardiography in asymptomaticBMPR2mutation carriers. The main objectives of this study were to evaluate the characteristics of asymptomaticBMPR2mutation carriers, assess their risk of occurrence of PAH and detect PAH at an early stage in this high-risk population.

Prevalence of pulmonary arterial hypertension (PAH) is higher in women, and the mechanism remains unclear. Prognosis is overall better for female compared with male patients with PAH. Pregnancy is associated with significant risk, mortality, and morbidity in patients with PAH; consensus guidelines recommend against pregnancy and counsel about early termination in these patients. Recent advances in treatment showed improvement in prognosis in small case reports of pregnant patients with PAH, particularly with the early use of parental prostacyclin. Education remains fundamental for women with PAH of childbearing age for pregnancy prevention as well as discussion about birth control methods.Copyright © 2018 Elsevier Inc. All rights reserved.

Pregnancy outcomes in patients with pulmonary hypertension remain poor despite advanced therapies. Although consensus guidelines recommend against pregnancy in pulmonary hypertension, it may nonetheless occasionally occur. This guideline document sought to discuss the state of knowledge of pregnancy effects on pulmonary vascular disease and to define usual practice in avoidance of pregnancy and pregnancy management. This guideline is based on systematic review of peer-reviewed, published literature identified with MEDLINE. The strength of the literature was graded, and when it was inadequate to support high-level recommendations, consensus-based recommendations were formed according to prespecified criteria. There was no literature that met standards for high-level recommendations for pregnancy management in pulmonary hypertension. We drafted 38 consensus-based recommendations on pregnancy avoidance and management. Further, we identified the current state of knowledge on the effects of sex hormones during pregnancy on the pulmonary vasculature and right heart and suggested areas for future study. There is currently limited evidence-based knowledge about both the basic molecular effects of sex hormones and pregnancy on the pulmonary vasculature and the best practices in contraception and pregnancy management in pulmonary hypertension. We have drafted 38 consensus-based recommendations to guide clinicians in these challenging topics, but further research is needed in this area to define best practices and improve patient outcomes.

The past 20 years have seen major advances in the diagnosis and management of pulmonary hypertension, a disease associated with significant morbidity and mortality. The 6th World Symposium in Pulmonary Hypertension (WSPH) took place in February 2018 and attempted to consolidate the current knowledge in the field into practical recommendations to help prioritize an action plan to improve patient outcomes and identify future research directions. In this review, we will summarize the highlights of the 6th WSPH proceedings, including revisions to the hemodynamic definitions and classification of the various types of pulmonary hypertension, genetic advances, approaches to risk stratification, and updated treatment algorithms.

Contemporary risk assessment tools categorise patients with pulmonary arterial hypertension (PAH) as low, intermediate or high risk. A minority of patients achieve low risk status with most remaining intermediate risk. Our aim was to validate a four-stratum risk assessment approach categorising patients as low, intermediate-low, intermediate-high or high risk, as proposed by the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) investigators.

Current European guidelines recommend periodic risk assessment for patients with pulmonary arterial hypertension (PAH). The aim of our study was to determine the association between the number of low-risk criteria achieved within 1 year of diagnosis and long-term prognosis.

Achievement of low-risk status is a treatment goal in pulmonary arterial hypertension (PAH). Risk assessment often is performed using multiparameter tools, such as the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) risk calculator. Risk calculators that assess fewer variables without compromising validity may expedite risk assessment in the routine clinic setting. We describe the development and validation of REVEAL Lite 2, an abridged version of REVEAL 2.0.Can a simplified version of the REVEAL 2.0 risk assessment calculator for patients with PAH be developed and validated?REVEAL Lite 2 includes six noninvasive variables-functional class (FC), vital signs (systolic BP [SBP] and heart rate), 6-min walk distance (6MWD), brain natriuretic peptide (BNP)/N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and renal insufficiency (by estimated glomerular filtration rate [eGFR])-and was validated in a series of analyses (Kaplan-Meier, concordance index, Cox proportional hazard model, and multivariate analysis).REVEAL Lite 2 approximates REVEAL 2.0 at discriminating low, intermediate, and high risk for 1-year mortality in patients in the REVEAL registry. The model indicated that the most highly predictive REVEAL Lite 2 parameter was BNP/NT-proBNP, followed by 6MWD and FC. Even if multiple, less predictive variables (heart rate, SBP, eGFR) were missing, REVEAL Lite 2 still discriminated among risk groups.REVEAL Lite 2, an abridged version of REVEAL 2.0, provides a simplified method of risk assessment that can be implemented routinely in daily clinical practice. REVEAL Lite 2 is a robust tool that provides discrimination among patients at low, intermediate, and high risk of 1-year mortality.ClinicalTrials.gov; No.: NCT00370214; URL: www.clinicaltrials.gov.Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

As an increasing number of women with pulmonary arterial hypertension (PAH) choose to become pregnant, outcomes in newborns have become a priority. The main purpose of this study was to compare the neonatal outcomes in pregnant women with PAH associated with heart disease.A single-center retrospective study was performed. Pregnancy with heart disease is divided into three groups: no PAH, mild PAH and severe PAH. Neonatal outcomes of pregnant women were compared among groups. Meanwhile, multivariable analyses were used to investigate the association between maternal PAH and adverse neonatal events.A total of 127 pregnant women with heart disease were enrolled. Of these, 82 (64.6%) had no PAH, 19 (15%) had mild PAH and 26 (20.4%) had severe PAH. The offspring of women with severe PAH had a higher risk of preterm delivery, low birth weight, neonatal respiratory distress syndrome (NRDS), neonatal intensive care unit (NICU) admission and recurrence of congenital heart disease (CHD). Compared to the women without PAH, only the risk of preterm delivery (32-36 weeks) and NICU admission were slightly higher in mothers with mild PAH; other neonatal events were similar. Multivariate regression analyses showed that the risk of preterm delivery (<37 weeks) increased with the increasing severity of maternal PAH, with an OR of 3.1 (95% CI, 1.1-8.8) for mild and 21.9 (95%CI, 4.8-99.4) for severe PAH. The same pattern was observed for NICU admission. Mothers with severe PAH were independently associated with low birth weight (OR 13, 95%CI 4.3-39, P < 0.001), NRDS (OR 17.9, 95%CI 5.5-58.9, P < 0.001) and recurrence of CHD (OR 4.47, 95%CI 1.7-11.6, P = 0.002).Pregnancy in women with severe PAH can significantly increase the risks of neonatal events. While neonatal outcomes in pregnant women with mild PAH were considered optimistic in the present study, a multidisciplinary management of PAH in pregnancy would be necessary to have consistently good outcomes.Copyright © 2023 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.

Pulmonary arterial hypertension is a rare disease that predominantly affects women. The pathophysiology of the disease is complex, with both genetic and hormonal influences. Pregnancy causes significant physiologic changes that may not be well tolerated with underlying pulmonary arterial hypertension, in particular leading to volume overload and increased pulmonary pressures. A multidisciplinary approach and careful monitoring are essential for appropriate management of pulmonary arterial hypertension during pregnancy. Nonetheless, outcomes are still poor, and pregnancy is considered a contraindication in patients with pulmonary arterial hypertension.Copyright © 2020 Elsevier Inc. All rights reserved.

The aim of this study was to investigate the effects of maternal pulmonary arterial hypertension (PAH) on fetal hemodynamics in the third trimester and to identify hemodynamic indicators associated with adverse maternal and fetal outcomes.We recruited 48 pregnant women with PAH in the third trimester and 32 women with normal pregnancies as controls matched for age and gestational week. Fetal growth and hemodynamic parameters were assessed by two-dimensional and color Doppler. All cases were followed up until delivery and maternal and fetal outcomes were collected. High throughput sequencing method was used to determine differential miRNA patterns in plasma exposed to pulmonary arterial hypertension (PAH) in pregnant women. We then performed the validated of key differentially expressed miRNAs by real-time PCR.Compared with the normal and mild PAH groups, resistance index (RI), pulsatility index (PI) of the fetal umbilical artery (UA) and quantitative ductus venosus (QDV) blood flow were increased in subjects with moderate to severe PAH, while PI and the ratio of peak systolic velocity (PSV) to end-diastolic velocity (EDV) (S/D) of the middle cerebral artery (MCA) were decreased. Compared with the normal group, subjects in the mild and moderate PAH groups had lower neonatal weight, shorter neonatal height, and higher preterm birth rates. In addition, miRNA sequencing data showed that PAH affected the levels of 23 miRNAs in plasma. At the same time, we showed that PAH significantly decreased the level of miR-1255a and increased the level of miR-548ar-3p by real-time PCR.In the group of pregnant women with moderate to severe pulmonary hypertension, there was a higher proportion of preterm births and low birth weight babies. Hemodynamic changes in the fetal UA, MCA, and ductus venosus (DV) during late pregnancy were associated with adverse fetal outcomes. At the same time, miRNA sequencing results showed that miR-1255a and miR-548ar-3p may play an important role in the development of PAH.© 2023 Wiley Periodicals LLC.

Studies focused on pregnant women with congenital heart disease (CHD)-associated pulmonary hypertension (PH) are scarce and limited by small sample sizes and single-center design. This study sought to describe the pregnancy outcomes in women with CHD with and without PH.Outcomes for pregnant women with CHD were evaluated retrospectively from 1993 to 2016 and prospectively from 2017 to 2019 from 7 tertiary hospitals. PH was diagnosed on the basis of echocardiogram or catheterization. The incidence of maternal death, cardiac complications, and obstetric and offspring complications was compared for women with CHD and no PH, mild, and moderate-to-severe PH.A total of 2220 pregnant women with CHD had completed pregnancies. PH associated with CHD was identified in 729 women, including 398 with mild PH (right ventricle to right atrium gradient 30-50 mm Hg) and 331 with moderate-to-severe PH (right ventricle to right atrium gradient >50 mm Hg). Maternal mortality occurred in 1 (0.1%), 0, and 19 (5.7%) women with CHD and no, mild, or moderate-to-severe PH, respectively. Of the 729 patients with PH, 619 (85%) had CHD-associated pulmonary arterial hypertension, and 110 (15%) had other forms of PH. Overall, patients with mild PH had better maternal outcomes than those with moderate-to-severe PH, including the incidence of maternal mortality or heart failure (7.8% versus 39.6%; <0.001), other cardiac complications (9.0% versus 32.3%; <0.001), and obstetric complications (5.3% versus 15.7%; <0.001). Brain natriuretic peptide >100 ng/L (odds ratio, 1.9 [95% CI, 1.0-3.4], =0.04) and New York Heart Association class III to IV (odds ratio, 2.9 [95% CI, 1.6-5.3], <0.001) were independently associated with adverse maternal cardiac events in pregnancy with PH, whereas follow-up with a multidisciplinary team (odds ratio, 0.4 [95% CI, 0.2-0.6], <0.001) and strict antenatal supervision (odds ratio, 0.5 [95% CI, 0.3-0.7], =0.001) were protective.Women with CHD-associated mild PH appear to have better outcomes compared with women with CHD-associated moderate-to-severe PH, and with event rates similar for most outcomes with women with CHD and no PH. Multimodality risk assessment, including PH severity, brain natriuretic peptide level, and New York Heart Association class, may be useful in risk stratification in pregnancy with PH. Follow-up with a multidisciplinary team and strict antenatal supervision during pregnancy may also help to mitigate the risk of adverse maternal cardiac events.

Current guidelines recommend oxygen (O) supplementation in patients with pulmonary hypertension (PH), despite scarce data on long-term O therapy (LTOT). The aim of this prospective, randomized, controlled trial was to investigate the effect of LTOT in patients with precapillary PH on exercise capacity, clinical parameters and hemodynamics. Patients with precapillary PH under stable therapy and O desaturations at rest and/or during exercise were randomized to receive LTOT (≥ 16 h/day) or no O (control group) for 12 weeks. The control group was offered LTOT after 12 weeks. The primary endpoint changes of 6-minute walking distance (6MWD) from baseline to 12 weeks was hierarchically tested: (1) pre-post primary and secondary intervention (2) intervention vs. control group. Secondary endpoints included changes in clinical parameters. Twenty patients were randomized (women n = 14, age 67 ± 11.4 years, mean pulmonary arterial pressure 39.7 ± 12.5 mmHg, 70% functional class III). 6MWD significantly improved by 42.2 ± 34.20 m (p = 0.003) within 12 weeks LTOT. The intervention group significantly improved in 6MWD (38.9 ± 33.87 m) compared to the control group (- 12.3 ± 21.83 m, p = 0.015). No consistent between-group differences in other parameters were found. LTOT was well tolerated and led to significant improvement of 6MWD. The effect of LTOT should be investigated in larger controlled-trials.© 2024. The Author(s).

We investigated whether domiciliary oxygen therapy (DOXT) increases exercise capacity and quality of life in patients with pulmonary arterial or distal chronic thromboembolic pulmonary hypertension (PAH/CTEPH) presenting with mild resting hypoxaemia and exercise-induced oxygen desaturation.

Pregnant individuals with pulmonary arterial hypertension (PAH) have significantly high risks of maternal and perinatal mortality. Profound changes in plasma volume, cardiac output and systemic vascular resistance can all increase the strain being placed on the right ventricle, leading to heart failure and cardiovascular collapse. Given the complex network of opposing physiological changes, strict contraception and reduction of hemodynamic fluctuations during pregnancy are important methods of minimizing the risk of maternal mortality and improving the outcomes following pregnancy. In this review, we discuss the recent research progress into pre-conception management and the various therapeutic strategies for pregnant individuals with PAH.

We aimed to investigate the prevalence of iron deficiency (ID) in congenital heart disease associated with pulmonary arterial hypertension (CHD-PAH) and to explore the influence of ID on CHD-PAH patients. What was associated with ID in these patients was also looked into.One hundred and fifty-three patients who were newly diagnosed with CHD-PAH were enrolled. Patients were divided into iron-deficient and iron-replete groups according to the following criteria. ID was defined as transferrin saturation <20% in male and transferrin saturation <25% in female. Clinical data of all participants were collected and compared. Logistic regression was performed to explore factors associated with ID in CHD-PAH.Thirty-nine percent of 153 CHD-PAH patients were founded with ID. Iron-deficient group had greater proportion of female patients, shorter six minutes walking distance (6-MWD), higher N-terminal pro-brain natriuretic peptide levels, lower creatinine levels, greater ratio of diastolic right ventricle diameter to left ventricle diameter. Female (OR = 15.44, 95%CI 4.91-48.54, p < .01), 6-MWD (OR = 0.99, 95%CI 0.98-1.00, p = .02) and mean right atrial pressure (OR = 1.13, 95%CI 1.02-1.26, p = .02) were independently associated with ID in the overall CHD-PAH patients. Menstruation was independently associated with ID in the female subgroup (OR = 3.88, 95%CI 1.09-13.84, p = .04).ID was highly prevalent in CHD-PAH patients. Worse exercise tolerance and right heart function were observed in iron-deficient patients with CHD-PAH. Female, 6-MWD, mean right atrial pressure and menstruation are important variables indicating the presence of ID in CHD-PAH.

Patients with systemic sclerosis (SSc) are frequently affected by iron deficiency, particularly those with pulmonary hypertension (PH). The first data indicate the prognostic importance of hypochromic red cells (% HRC) > 2% among patients with PH. Hence, the objective of our study was to investigate the prognostic value of % HRC in SSc patients screened for PH.In this retrospective, single-center cohort study, SSc patients with a screening for PH were enrolled. Clinical characteristics and laboratory and pulmonary functional parameters associated with the prognosis of SSc were analyzed using uni- and multivariable analysis.From 280 SSc patients screened, 171 could be included in the analysis having available data of iron metabolism (81% female, 60 ± 13 years of age, 77% limited cutaneous SSc, 65 manifest PH, and 73 pulmonary fibrosis). The patients were followed for 2.4 ± 1.8 (median 2.4) years. HRC > 2% at baseline was significantly associated with worse survival in the uni- (p = 0.018) and multivariable (p = 0.031) analysis independent from the presence of PH or pulmonary parenchymal manifestations. The combination of HRC > 2% and low diffusion capacity for carbon monoxide (DLCO) ≤ 65% predicted was significantly associated with survival (p < 0.0001).This is the first study reporting that HRC > 2% is an independent prognostic predictor of mortality and can possibly be used as a biomarker among SSc patients. The combination of HRC > 2% and DLCO ≤ 65% predicted could serve in the risk stratification of SSc patients. Larger studies are required to confirm these findings.© 2023. The Author(s).

Iron deficiency (Fe) has been shown to be common in patients with group 1 or pulmonary arterial hypertension (PAH). Several studies have shown a negative impact of Fe on clinical and haemodynamic parameters of the disease, but data from individual studies have not been strong enough to lead to incorporation of the finding of Fe into prognostic or therapeutic algorithms. The goal of this meta-analysis was to combine data from available studies to better define any associations between Fe and established variables of prognostic importance in PAH.A literature search identified nine studies with extractable data relevant to the study questions. The impact of Fe upon the following parameters was evaluated: 6-minute walk distance (6MWD), WHO-functional class, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, echocardiography, and findings from right heart catheterisation (RHC). Pooled results were reported as mean difference or risk difference with 95% confidence intervals utilising a random effects modeling approach.Fe in the PAH population was common (47% of cases) and was associated with cardiovascular dysfunction (lower tricuspid annular plane systolic excursion [TAPSE], elevated NT-proBNP, and lower mixed venous oxygen saturation) and with reduction in functional capacity (lower 6MWD and higher functional class).This meta-analysis strengthens the relationships between Fe and several markers of poor outcome in PAH. Fe in patients with PAH warrants further scrutiny and merits consideration as a cause of clinical deterioration. Even though causation and longitudinal relationships between Fe and PAH could not be identified, effect of Fe on factors that affect disease prognosis is noteworthy and worthy of more focussed studies.Copyright © 2022 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Data about anticoagulation in pulmonary arterial hypertension (PAH) patients are inconsistent. The objective of this study was to examine the impact of adjunctive oral anticoagulants in patients with PAH through meta-analysis, and to further assess whether response differs by PAH subtype.

Our aim with this review is to provide practical advice and management support for nurses and other healthcare practitioners in managing fluid retention in adults with right heart failure (RHF) due to pulmonary arterial hypertension (PAH). Vigilant management of RHF is important for maintaining patient quality of life, as fluid overload can lead to abdominal bloating (ascites) and peripheral oedema, which also has a major impact on patients’ morbidity and mortality. Patients with RHF should be assessed regularly for signs of fluid retention. If fluid overload develops, it is important to determine whether it is caused by the progression of PAH, a side effect of PAH-specific treatment, or another drug or comorbid condition, as this affects both the prognosis and the management strategy. Right heart failure can be treated with both pharmacological and non-pharmacological interventions to reduce fluid retention; including altering fluid and salt intake, weight monitoring, and use of diuretics. All patients on diuretics should be regularly monitored for renal dysfunction and electrolyte imbalance and given advice on how to manage the side effects associated with diuretic use. Fluid retention is often assessed and treated in clinical practice by specialist nurses, who act as a key patient contact providing advice and information on symptom management. This review provides an overview of the challenges related to fluid retention, including strategies to help patients manage symptoms and side effects of treatment.

Previous studies have reported mortality rates of up to 56% associated with pregnancy in pulmonary arterial hypertension (PAH) but the management of this disease has changed considerably in recent years. We compiled a multinational, prospective registry to examine the contemporary outcome of pregnancies in patients with PAH. During a 3-yr period, the 13 participating centres reported 26 pregnancies. Three (12%) females died and one (4%) developed right heart failure requiring urgent heart-lung transplantation. There were eight abortions; two spontaneous and six induced. 16 (62%) pregnancies were successful, i.e. the females delivered healthy babies without complications. These females had well controlled PAH (pulmonary vascular resistance (PVR) 500 ± 352 dyn·s·cm(-5)); eight of them were long-term responders to calcium channel blockers. In contrast, the females who died or required transplantation had poorly controlled PAH (PVR 1,667 ± 209 dyn·s·cm(-5)). Pregnancy remains associated with a substantial mortality rate in PAH. However, our results indicate that the outcome of pregnancy in PAH has improved, at least when PAH is well controlled, and particularly in long-term responders to calcium channel blockers. These data must be confirmed by larger series before the general recommendation to avoid pregnancy in all patients with PAH is reconsidered.

In patients with pulmonary hypertension, pregnancy is associated with a high risk of maternal death. Such patients are counselled to avoid pregnancy, or if it occurs, are offered early interruption. Some patients, however, decide to continue with their pregnancy and others may present with symptoms for the first time whilst pregnant. Pulmonary vasodilator therapy provides a treatment option for these high-risk patients. The present study describes three patients with pulmonary arterial hypertension of various aetiologies who were treated with the prostacyclin analogue iloprost during pregnancy, and the post-partum period. Nebulised iloprost commenced as early as 8 weeks of gestation and patients were admitted to hospital between 24-36 weeks of gestation. All pregnancies were completed with a duration of between 25-36 weeks and all deliveries were by caesarean section under local anaesthetic. All patients delivered children free from congenital abnormalities, and there was no post-partum maternal or infant mortality. In conclusion, although pregnancy is strongly advised against in those with pulmonary hypertension, the current authors have achieved a successful outcome for mother and foetus with a multidisciplinary approach and targeted pulmonary vascular therapy.

Maternal heart disease has emerged as a major threat to safe motherhood and women's long-term cardiovascular health. In the United States, disease and dysfunction of the heart and vascular system as "cardiovascular disease" is now the leading cause of death in pregnant women and women in the postpartum period (1, 2) accounting for 4.23 deaths per 100,000 live births, a rate almost twice that of the United Kingdom (3, 4). The most recent data indicate that cardiovascular diseases constitute 26.5% of U.S. pregnancy-related deaths (5). Of further concern are the disparities in cardiovascular disease outcomes, with higher rates of morbidity and mortality among nonwhite and lower-income women. Contributing factors include barriers to prepregnancy cardiovascular disease assessment, missed opportunities to identify cardiovascular disease risk factors during prenatal care, gaps in high-risk intrapartum care, and delays in recognition of cardiovascular disease symptoms during the puerperium. The purpose of this document is to 1) describe the prevalence and effect of heart disease among pregnant and postpartum women; 2) provide guidance for early antepartum and postpartum risk factor identification and modification; 3) outline common cardiovascular disorders that cause morbidity and mortality during pregnancy and the puerperium; 4) describe recommendations for care for pregnant and postpartum women with preexisting or new-onset acquired heart disease; and 5) present a comprehensive interpregnancy care plan for women with heart disease.

Due to the aging world population and increasing trend in clinical practice to treat patients with multiple drugs, adverse events (AEs) are becoming a major challenge in drug discovery and public health. In particular, identifying AEs caused by drug combinations remains a challenging task. Clinical trials typically focus on individual drugs rather than drug combinations and animal models are unreliable. An added difficulty is the combinatorial explosion in the number of possible combinations that can be made using the increasingly large set of FDA approved chemicals. We present a statistical and computational technique for identifying AEs caused by two-drug combinations. Taking advantage of the large and increasing data deposited in FDA's postmarketing reports, we demonstrate that the task of predicting AEs for 2-drug combinations is amenable to the Likelihood Ratio Test (LRT). Our pAERS database constructed with LRT contains almost 77 thousand associations between pairs of drugs and corresponding AEs caused solely by drug-drug interactions (DDIs). The DDIs stored in pAERS complement the existing data sets. Due to our stringent statistical test, we expect many of the associations in pAERS to be unrecorded or poorly documented in the literature.