Severe Pulmonary Arterial Hypertension Research Articles

Pulmonary arterial hypertension due to ventriculoatrial shunts: A case report and literature review

Cardiopulmonary complications are infrequent in patients with ventriculoatrial shunts (VAS). We report the case of an 18-year-old man with congenital hydrocephalus who developed pulmonary arterial hypertension (PAH) in the long-term follow-up after a VAS procedure. He presented with progressive exertional dyspnea, stabbing chest pain and acral cyanosis. Echocardiography showed severe PAH and a digitiform mass adhered to the distal catheter. A ventilation/perfusion scan suggested chronic pulmonary embolisms. Anticoagulation with intravenous heparin was started and thrombus resolution was achieved, but PAH remained. It is necessary to bear in mind complications linked to VAS when treating a patient with this device.

Cytokine profiling in pulmonary arterial hypertension: the role of redox homeostasis and sex

Pulmonary arterial hypertension (PAH) is a fatal disease with a well-established sexual dimorphism. Activated inflammatory response and altered redox homeostasis, both known to manifest in a sex-specific manner, are implicated in the pathogenic mechanisms involved in PAH development. This study aimed to evaluate the impact of sex and plasma redox status on circulating cytokine profiles. Plasma oxidation-reduction potential (ORP), as a substitute measure of redox status, was analyzed in male and female Group 1 PAH and healthy subjects. The profiles of 27 circulating cytokines were compared in 2 PAH groups exhibiting the highest and lowest quartile for plasma ORP, correlated with clinical parameters, and used to predict patient survival. The analysis of the PAH groups with the highest and lowest ORP revealed a correlation between elevated cytokine levels and increased oxidative stress in females. In contrast, in males, cytokine expressions were increased in the lower oxidative environment (except for IL-1b). Correlations of the increased cytokine expressions with PAH severity were highly sex-dependent and corresponded to the increase in PAH severity in males and less severe PAH in females. Machine learning algorithms trained on the combined cytokine and redox profiles allowed the prediction of PAH mortality with 80% accuracy. We conclude that the profile of circulating cytokines in PAH patients is redox- and sex-dependent, suggesting the vital need to stratify the patient cohort subjected to anti-inflammatory therapies. Combined cytokine and/or redox profiling showed promising value for predicting the patients' survival.

Full Recovery of Right Ventricular Systolic Function in Children Undergoing Bilateral Lung Transplantation for Severe PAH

<h3>Purpose</h3> We investigated whether RV function recovers in children with pulmonary arterial hypertension (PAH) and RV failure undergoing lung transplantation (LuTx). The major research questions were how completely and how quickly after LuTx systolic RV function recovers in children with PAH. <h3>Methods</h3> Prospective observational study of 15 consecutive children (age range: 1.9-17.6 years) with severe PAH who underwent bilateral lung transplantation between December 2013 and January 2021. We performed advanced echocardiography (Echo) and cardiac magnetic resonance imaging (MRI), followed by conventional and strain analysis, pre and ∼6 weeks post LuTx. <h3>Results</h3> All patients had PAH, i.e. group 1 pulmonary hypertension: idiopathic (n=6), heritable (n=4), PAH-congenital heart disease (n=2), pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis (PVOD/PCH; n=3). Six weeks after LuTx, RV/LV endsystolic diameter ratio (Echo), RV volumes and systolic RV function (RVEF 63 vs. 30 %; p<0.05) by MRI completely normalized, even in children with severe RV failure (RVEF < 40%). The echocardiographic end-systolic LV eccentricity index nearly normalized post LuTx (1.0 vs. 2.0, p<0.0001) while RV hypertrophy regressed more slowly and was still evident. We found especially the end-systolic RV/LV ratios by Echo (RV/LV diameter; 0.6 vs. 2.6) or MRI (RV/LV volumes: 0.8 vs. 3.4 excellent diagnostic tools (p<0.05): Together with RVEF by MRI, these ratios were superior to tricuspid annular plane systolic excursion (TAPSE; p>0.05) in assessing global systolic RV dysfunction. Moreover, children with severe PAH had reduced RV 2D longitudinal strain (Echo, MRI; p<0.05) and decreased RV 2D radial and circumferential strain (MRI; p<0.01), all of which greatly improved following LuTx. One year survival after LuTx for PAH was 100% (15/15 patients alive; 1 retransplant 9 months status post LuTx because of cellular rejection). No PAH LuTx candidate died on the transplant waiting list. <h3>Conclusion</h3> We demonstrate full recovery of RV systolic function in children within two months after LuTx for severe PAH, independently of the patients' age, weight, and hemodynamic compromise preceding the LuTx. Even in end-stage pediatric PAH with poor RV function and low cardiac output, LuTx should be preferred over heart-lung transplantation.

Meeting abstracts from the 15th international conference on neonatal and childhood pulmonary vascular disease

Meeting abstracts from the 15th international conference on neonatal and childhood pulmonary vascular disease

Right Heart Reverse Remodeling Correlates with NT-proBNP Outcomes Among Pulmonary Arterial Hypertension Patients on Combination Therapy

<h3>Purpose</h3> Combination therapy is the current standard for severe pulmonary arterial hypertension (PAH). Few studies have characterized reverse remodeling achievable with therapy, and in particular, how it correlates with prognostic trends in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. We evaluated the longitudinal impact of PAH combination therapy on echocardiographic right heart parameters and observed how reverse remodeling correlates with a prognostic indicator of treatment response. <h3>Methods</h3> Thirty-two adults (age, 32±9years) with newly diagnosed PAH were initiated on combination therapy and had transthoracic echocardiograms performed prior to, and at least 3 months after, starting therapy. Pre- and follow-up NT-proBNP values were collected and speckle-tracking strain analysis was applied to echocardiogram images. Paired samples t-test was used to evaluate the statistical difference between baseline and follow-up measurements. <h3>Results</h3> After a mean 2.7 years, there was a significant decrease in mean RV basal diameter from 4.6cm to 4.2cm (p=0.03) and mean right atrial area from 23.6cm² to 19.8cm² (p<0.01). RV fractional area change (RVFAC) increased from 21% to 31% (p<0.01) and mean RV free wall strain (RVFWS) improved from -11.4% to -15.8% (p<0.01). Prior to therapy, 63% of patients had elevated NT-proBNP levels (>900pg/mL). By follow-up, there was a greater improvement in RVFAC among patients who maintained or achieved a normal NT-proBNP level with therapy compared to those whose biomarker level increased or remained elevated (+0.10% vs +0.003%, p=0.03). RVFWS improved to a greater extent in the former group compared to the latter, though this did not reach statistical significance (-5.32% vs. -0.86%, p=0.07). Five out of the 6 patients who died during follow-up maintained elevated NT-proBNP levels despite therapy. Half were on aggressive regimens including intravenous prostacyclin therapy. <h3>Conclusion</h3> While combination PAH therapy was associated with improved RV structure and function parameters among our cohort; patients with persistently elevated or deteriorated NT-proBNP levels demonstrated less reverse remodeling and had increased mortality. These findings highlight a need for novel future therapies that target right heart-specific remodeling pathways in high-risk PAH patients.

Novel Bridge to Recovery: Right Ventricular Assist Device for Primary Graft Dysfunction in Pediatric Lung Transplantation

<h3>Introduction</h3> Primary graft dysfunction (PGD) is an early complication after lung transplantation (LTx). Extracorporeal membrane oxygenation (ECMO) is used for rescue of refractory hypoxemia due to severe PGD, although ventricular assist device support in PGD after LTx is less well documented. <h3>Case Report</h3> A 9 year old boy with Trisomy 21 underwent bilateral LTx for severe pulmonary arterial hypertension (PAH). Mean PA pressure was 73 mmHg, with a hypertrophied right ventricle (RV) and mild-moderately reduced RV function. He was transplanted with size matched lungs, blood type O- into O+. No HLA antibodies were identified. Marked vasoplegia was seen 8 hours post-operatively. Chest x-ray showed interstitial markings consistent with PGD. At 36 hours, P/F ratio had dropped to 59. Systemic inflammatory response (SIRS) and RV dysfunction resulted in acute kidney injury with Cr 256 µmol/L and hepatic dysfunction with ALT > 4,600. At 40 hours, right ventricular assist device (RVAD) with oxygenator was placed via central cannulation to the main PA and right atrium (RA). Peripheral sites were not available due to prior ECMO. Stenosis was seen of the right upper pulmonary vein. Oxygenation, lung aeration, and biochemical markers improved over 11 days after which he was weaned from RVAD and decannulated. At 8 months post-LTx, he is doing well. Graft function is excellent with most recent FEV₁ at 71% predicted, versus 37% pre-transplant. Acute kidney injury has resolved and liver function has returned to normal. <h3>Summary</h3> This case presents a novel successful approach in providing bridge to recovery for PGD after LTx and RV dysfunction in a pediatric patient with Down syndrome. This was a unique scenario with no peripheral cannulation access, RV systolic and diastolic dysfunction, and multi-system sequelae. Central cannulation (RA-PA) with RVAD/oxygenator allowed adequate support for the PGD to clear. To our knowledge, this is the first publication on RVAD/oxygenator use in pediatric lung PGD. This also documents the first patient with Down syndrome to receive a bilateral LTx in Canada. It is unclear if Down syndrome-related factors increased the risk for PGD; PV stenosis and SIRS may have played a role. Note that RA to aortic cannulation is not advised due to the need to maintain flow to the PAs, since there is no longer bronchial circulation supplying the lungs after transplant.

Anaesthetic management of a case of large ASD with severe pulmonary hypertension\u2014case presentation

BackgroundAtrial septal defect is the most common acyanotic congenital cardiac anomaly in the adults after bicuspid aortic valve with high prevalence in females. Major challenges in the management of large ASD with severe pulmonary hypertension includes hypoxemia, hypercarbia, hypothermia leading to reversal of shunt (Eisenmenger syndrome), fatal arrhythmias and congestive heart failure.Case presentationWe report the successful management of the case of 44-year-old female patient with large ASD and severe pulmonary arterial hypertension posted for total abdominal hysterectomy with salpingectomy. She had history of palpitations with exertional dyspnoea and history of abnormal uterine bleeding with failed medical treatment. Echocardiography showed large OS-ASD (24 mm) with left to right shunt, moderate TR, severe PAH with estimated RVSP 60 mmHg, LVEF 50% and grossly dilated RA/RV. She underwent total abdominal hysterectomy with salpingectomy under regional anaesthesia with prophylactic use of adrenaline infusion.ConclusionsCardiac patients for non-cardiac surgery can be managed under regional anaesthesia.

Pulmonary Arterial Hypertension and Consecutive Right Heart Failure Lead to Liver Fibrosis.

Hepatic congestion occurs in patients with right heart failure and can ultimately lead to liver fibrosis or cardiac cirrhosis. Elevated pulmonary arterial pressure is found in patients with hepatic congestion. However, whether pulmonary arterial hypertension (PAH) can be a cause of liver fibrosis is unknown. The aim of this study was to investigate whether rats in the SuHx model with severe PAH develop liver fibrosis and to explore the mechanisms of congestive hepatic fibrosis both in rats and humans. To achieve this, PAH was induced in six to eight-week old male Sprague Dawley rats by a single subcutaneous injection of the VEGFR 2 inhibitor SU5416 and subsequent hypoxia for 3 weeks, followed by a 6-week period in room air. SuHx-exposed rats developed severe PAH, right ventricular hypertrophy (RVH), and consecutive right ventricular failure. Cardiac magnetic resonance imaging (MRI) and histological analysis revealed that PAH rats developed both hepatic congestion and liver fibrosis. Gene set enrichment analysis (GSEA) of whole liver RNA sequencing data identified a hepatic stellate cell specific gene signature in PAH rats. Consistently, tissue microarray from liver of patients with histological evidence of hepatic congestion and underlying heart disease revealed similar fibrogenic gene expression patterns and signaling pathways. In conclusion, severe PAH with concomitant right heart failure leads to hepatic congestion and liver fibrosis in the SU5416/hypoxia rat PAH model. Patients with PAH should therefore be screened for unrecognized liver fibrosis.

Clipping of an Aortopulmonary Window in a Small Neonate With Bronchial Bleeding: A Simple Solution for a Complex Condition

Although the conventional treatment of aortopulmonary (AP) window consists of reconstructive surgery with the use of cardiopulmonary bypass (CPB), some conditions like low birth weight or active respiratory tract bleeding may lead to diverting therapeutic options. We present a case of a premature 1.9 kg neonate with severe pulmonary arterial hypertension based on the association of an AP window and large patent ductus arteriosus. Because of intrabronchial hemorrhage, a conservative strategy was chosen excluding the need for heparinization and CPB. Through median sternotomy, the ductus arteriosus and AP window were clipped, effectively occluding both shunts. The postoperative course was uneventful with a rapid decrease of pulmonary artery pressure. Although classical surgical reconstruction is still advocated as primary therapy, this case illustrates the suitability of an alternative approach without the need for CPB and full heparinization in a patient with an increased risk of bleeding complications.

Pregnancy outcome analysis of 94 patients with pulmonary arterial hypertension during pregnancy.

The aim of the study was to analyze the pregnancy outcomes of patients with pulmonary arterial hypertension to provide a reference for clinical diagnosis and treatment. Clinical data of 94 patients with a pregnancy complicated by pulmonary hypertension were retrospectively analyzed. The means and percentages of the pregnancy outcomes were calculated, and the analysis of variance, Chi-square test, and Fisher's exact test were applied for comparison. The pregnancy outcomes were less favorable in the severe pulmonary arterial hypertension group compared to the mild and moderate groups. The more severe the pulmonary arterial hypertension, the worse the heart function. A poorer heart function was associated with a poorer prognosis across different pregnancy outcomes. A pregnancy with more severe pulmonary arterial hypertension and worse cardiac function has a poorer maternal and infant prognosis and pregnancy outcome. Cesarean section is the preferred delivery method for patients with severe pulmonary arterial hypertension, whereas vaginal delivery is preferred for patients with mild or moderate pulmonary arterial hypertension and good cardiac function.

Prevalence of pulmonary arterial hypertension in severe chronic obstructive pulmonary disease patients attending tertiary care centre Ernakulam

Background: Chronic obstructive pulmonary disease (COPD) is an irreversible bronchial inflammation of lung airways and parenchyma. Various factors play an important role in occurrence and severity of pulmonary arterial hypertension (PAH), a common in severe COPD. The objective of the study is to know the proportion of PAH in patients with severe COPD and to find the association between various factors.Methods: 180 cases of severe COPD patients admitted in Government Medical College Ernakulum from January 2019-December 2019, were enrolled into this cross-sectional descriptive study. Subject’s history, clinical examination, anthropometric measurements, vitals, Arterial Blood Gas (ABG) analysis were done.Results: Among 180 subjects, 148 (82.22%) had mild PAH, 22 (12.22%) subjects had moderate PAH and 10 (5.56%) had severe PAH. Use of accessory muscle was the most elicited sign in the study with 174 (96.67%). 170 (94.44%) had cough and 169 (93.89%) had breathlessness which were the most reported symptoms. Demographic variables and clinical features had no significant mean pulmonary artery pressure (mPAP) association. Grade 3 PAH groups were elder than others, which was statistically significant (p&lt;0.047). FEV1, Oxygen Saturation and ejection fraction were lowest in grade 3 PAH subjects. Respiratory rate, hemoglobin, PCV, tricuspid velocity, PaCO2 were highest in grade 3 PAH subjects being statistically significant (p&lt;0.0001).Conclusions: In our study, majority of severe COPD patients had mild PAH. There was an independent correlation between respiratory rate, hemoglobin, PCV, tricuspid regurgitant velocity and PaCO2 with severity of PAH.

Prevalence of musculoskeletal pain and its impact on quality of life and functional exercise capacity in patients with pulmonary arterial hypertension

BackgroundIn pulmonary arterial hypertension (PAH), pathophysiological consequences of the disease and the drugs used to treat PAH may adversely affect musculoskeletal system. Aim of the study was to evaluate musculoskeletal pain prevalence and its impact on quality of life (QoL) and exercise capacity in PAH patients. Methods61 PAH patients were evaluated with Nordic Musculoskeletal Questionnaire (NMQ) for musculoskeletal pain presence, EmPHasis-10 and Minnesota Living with Heart Failure Questionnaire (MLHFQ) for QoL, 6-min walk test (6MWT) for functional exercise capacity and International Physical Activity Questionnaire- Short Form (IPAQ-SF) for physical activity participation. Results77% of PAH patients reported musculoskeletal pain. Pain prevalence was highest at low back (38%), followed by knees (36%), shoulders (36%) and neck (33%). Hemodynamic indicators of PAH severity were associated with pain presence in various parts of the body. Patients receiving any PAH-specific drug were more likely to experience pain compared to the patients whose drug therapy has not yet been initiated (RR = 1.6–2.0). Pain presence in neck, shoulder, low back and knees significantly correlated to worse QoL scores in both EmPHasis-10 and MLHFQ (p < 0.05). Pain presence in knees had the strongest influence on QoL, and it was the only significant correlate of 6MWT (r = −0.424) and IPAQ-SF (r = −0.264) (p < 0.05). ConclusionsMusculoskeletal pain is a common complaint in PAH patients, which significantly impairs QoL and physical functioning. Treatment strategies should include a more comprehensive assessment for musculoskeletal pain complaints of these patients and address pain presence accordingly, which may help providing a better management for PAH.

Advanced Circulatory Support and Lung Transplantation in Pulmonary Hypertension.

Pulmonary arterial hypertension (PAH) is a progressive fatal disease. Although medical therapies have improved the outlook for these patients, there still exists a cohort of patients with PAH who are refractory to these therapies. Lung transplantation (LT), and in certain cases heart-lung transplantation (HLT), is a therapeutic option for patients with severe PAH who are receiving optimal therapy yet declining. ECMO may serve as a bridge to transplant or recovery in appropriate patients. Although, the mortality within the first 3 months after transplant is higher in PAH recipients than the other indications for LT, and the long-term survival after LT is excellent for this group of individuals. In this review, we discuss the indications for LT in PAH patients, when to refer and list patients for LT, the indications for double lung transplant (DLT) versus HLT for PAH patients, types of advanced circulatory support for severe PAH, and short and long-term outcomes in transplant recipients with PAH.

Surgical management of giant pulmonary artery aneurysms in patients with severe pulmonary arterial hypertension.

Giant aneurysm of the pulmonary artery (PAA) is an extremely rare condition that may develop in patients with pulmonary arterial hypertension (PAH) which may be complicated by rupture, dissection or intravascular thrombus formation. The aim of this study was to examine available literature with regard to surgical strategies in patients undergoing transplantation for PAH with PAA. These patients were traditionally considered for heart-lung transplantation but more recently, there have been reports of successful lung transplantation with reconstruction of the pulmonary artery. Unless there is a mandatory indication for heart-lung transplantation, patients with PAH and PAA can undergo lung transplantation and reconstruction of the pulmonary artery without compromising the outcome.

Impact of Pulmonary Arterial Hypertension on Systemic Inflammation, Cardiac Injury and Hemodynamics in Sepsis: A Retrospective Study From MIMIC-III

BackgroundSepsis and pulmonary arterial hypertension (PAH) may both present in a single patient in the intensive care unit. The impact of PAH on the sepsis process is not well understood. Here we assess the effect of PAH in patients with sepsis from multiple perspectives. MethodsPatients with sepsis with or without PAH underwent propensity score matching according to age, sex and ethnicity. Clinical complications, hemodynamics, and laboratory examinations, including heart injury and inflammation, were compared between the 2 groups. We aimed to model the relationship between the severity of PAH and systemic inflammation levels using linear regression analysis. Factors associated with 28-day and one-year mortality in patients with sepsis with PAH were also analyzed using binary logistic regression. ResultsA total of 285 pairs of patients with sepsis with or without PAH were included in the analysis. There were no significant differences in the C-reactive protein (CRP), white blood cell (WBC), or lactate levels or neutrophil percentage between the 2 groups, and the mean pulmonary arterial pressure and N-terminal pro b-type natriuretic peptide (NTproBNP) level did not correlate with CRP, WBC or lactate. The cardiac injury indexes were significantly higher in the PAH group. Lower mean arterial pressure was found in patients with PAH. Longer ventilation duration was a risk factor for, while obesity was protective against, both short- and long-term mortality in patients with sepsis with PAH. ConclusionsPAH had little effect on the inflammation profile in sepsis, but it may worsen the sepsis outcome by impairing cardiac function and subsequent hemodynamic stability.

Thiamine-responsive, life-threatening, pulmonary hypertensive crisis with encephalopathy in young infants: A case series.

Thiamine (Vitamin B1) deficiency (TD), although reduced in incidence, is still seen in infants. We describe a rarely reported form of infantile TD with life-threatening pulmonary hypertensive crisis and severe encephalopathy, with dramatic response to thiamine supplementation. Study design: Descriptive case series. Six young infants with mean age 76 days (range 1-3 months), manifesting rapidly progressive encephalopathy and cardio-pulmonary arrest were included. All infants underwent cardiac, neuroimaging and metabolic evaluations. All six infants had similar presentation with severe pulmonary arterial hypertension (PAH), hypotensive shock, metabolic acidosis and severe encephalopathy. All infants were exclusively breast-fed. Thiamine treatmwnt resulted in dramatic improvement in haemodynamic and neurological function in all the infants. There were no major neurological deficits on follow up. A high index of suspicion is warranted for this rarely described form of TD, as early identification helps in preventing mortality and morbidity.

Plasma level of antimony correlates with pulmonary arterial hypertension severity

It is unknown if environmental antimony exposure influences pulmonary arterial hypertension (PAH) and right ventricular function. We performed a pilot study to evaluate antimony levels in 20 PAH patients and 10 controls. Also, we explored the correlation of antimony level with PAH prognostic hemodynamic markers. Antimony blood and plasma levels were significantly higher in PAH patients when compared to controls [blood: PAH mean ± SD (95%CI) 1.3 ± 0.6 (1.0–1.5) ng/ml vs. control mean ± SD (95%) 0.7 ± 0.5 (0.4–1.0) ng/ml, p = 0.017] [plasma: PH mean ± SD (95%CI) 2.6 ± 1 (2.2–3.1) ng/ml vs. control mean ± SD (95%CI) 1.5 ± 0.8 (1.0–2.0) ng/ml, p = 0.004]. Also, antimony blood and plasma levels were significantly higher in idiopathic-PAH patients and non-idiopathic PAH when compared to controls. There was a trend for higher blood and plasma antimony levels in idiopathic PAH [blood1.6 ± 0.6 (1.1–2.1) ng/ml and plasma 3.1 ± 1.2 (2.2–4.1) ng/ml] when compared to non-idiopathic PAH [blood 1.1 ± 0.6(0.8–1.4) ng/ml and plasma 2.5 ± 0.9(2–2.9) ng/ml], but it did not reach statistical significance. There was a significant correlation between plasma antimony level and all the prognostic hemodynamic parameters of PAH including mRAP (r = 0.47, p = 0.036), CO (r = −0.50, p = 0.026), CI (r = −0.54, p = 0.014), PVR (r = 0.52, p = 0.019), and SvO2 (r = -0.54, p = 0.016).

An Observational Data Analytical Research on Pediatric Cardiomegaly as a Predictor of Structural or Functional Heart Diseases

Background: Chest X-ray (CXR) is a routine, noninvasive test advised in a plethora of pediatric non-cardiac conditions such as bronchopneumonia, respiratory distress, failure to thrive, suspected tuberculosis, and for preoperative anesthesia clearance. Finding of cardiomegaly (CM) on CXR is a common cause of referral to a pediatric cardiologist. The question lies in its significance: whether CM in CXR corroborates with cardiac disease (s), structural or functional. Materials and Methods: The data of 229 children (median age: 6 months), referred to pediatric cardiology unit for echocardiography with CXR depicting CM over a period of 2 years (June 2019 to July 2021), were retrospectively reviewed. Clinical and laboratory findings, CXR, and echocardiography were analyzed for all children to determine the positive predictive value of CM in CXR to detect cardiac disease. Echocardiography was taken as gold standard to reach the cardiac diagnosis. Results: True CM was noted in 85% (Group A), whereas 15% had false CM (Group B). Group A comprised structural heart defect in 71.7% and ventricular dysfunction in 13.3%. Less common causes were severe anemia, hypertensive heart failure, arrhythmogenic cardiomyopathy, diphtheritic cardiomyopathy, multisystem inflammatory syndrome in children, pericardial effusion, thiamine deficiency, and severe idiopathic pulmonary arterial hypertension. In Group B, the most common reasons for false diagnosis were expiratory film (n = 18), thymic shadow (n = 12), and chest deformity and mediastinal mass (n = 2 each). Conclusion: CM in CXR strongly correlates with cardiac involvement and has a high positive predictive value. Combining clinical, laboratory, and CXR interpretation enables the pediatrician to achieve a rapid functional diagnosis. Medical stabilization can be initiated with this knowledge pending the availability of echocardiography in resource-limited areas. Detailed evaluation at a pediatric cardiac center should be completed to reach a final diagnosis in all such patients. In the absence of congenital heart disease, known acquired causes leading to cardiac compromise should be actively looked for.

Epidemiology and Disease Management of Pulmonary Hypertension During The Last Two Decades in Japan

Background Pulmonary arterial hypertension (PAH) is a rare, progressive disease. The treatment landscape for PAH in Japan has evolved considerably in recent years, but there is limited knowledge of the changes in treatment practices or patient characteristics. Objectives To evaluate the changes in characteristics and initial treatments for PAH in Japan over time. Methods We used data from the Japan Pulmonary Hypertension Registry (JAPHR) to compare patient characteristics and treatment practices between 2008–2015 (316 patients) and 2016–2020 (315 patients). Results The age (mean ± standard deviation) at diagnosis increased from 47.9 ± 16.7 years in 2008–2015 to 52.7 ± 16.9 years in 2016–2020. The mean pulmonary arterial pressure decreased from 45.4 ± 15.0 to 38.6 ± 13.1 mmHg (mean ± standard deviation). Idiopathic/hereditary PAH was the commonest etiology in both periods (50.0% and 51.1%). The proportion of patients prescribed oral/inhaled combination therapies increased from 47.8% to 57.5%. Oral/inhaled combination therapies were frequently prescribed to patients with congenital heart disease-related PAH (81.8%). There was no significant trend in prescribing practices based on French low-risk criteria: among patients with 0, 1, 2, 3, or 4 criteria, 53.8%, 68.8%, 52.8%, 66.7%, and 39.4% were prescribed oral/inhaled combination therapies, and 0%, 16.7%, 27.0%, 17.3%, and 15.2% were prescribed oral/inhaled monotherapies, respectively. Macitentan, tadalafil, selexipag, and epoprostenol were the most frequently prescribed drugs. Conclusions The severity of PAH decreased over time in Japan. Oral/inhaled combination therapies were generally preferred. Physicians generally prescribed therapies after considering the patients’ hemodynamics and clinical severity. Pulmonary arterial hypertension (PAH) is a rare, progressive disease. The treatment landscape for PAH in Japan has evolved considerably in recent years, but there is limited knowledge of the changes in treatment practices or patient characteristics. To evaluate the changes in characteristics and initial treatments for PAH in Japan over time. We used data from the Japan Pulmonary Hypertension Registry (JAPHR) to compare patient characteristics and treatment practices between 2008–2015 (316 patients) and 2016–2020 (315 patients). The age (mean ± standard deviation) at diagnosis increased from 47.9 ± 16.7 years in 2008–2015 to 52.7 ± 16.9 years in 2016–2020. The mean pulmonary arterial pressure decreased from 45.4 ± 15.0 to 38.6 ± 13.1 mmHg (mean ± standard deviation). Idiopathic/hereditary PAH was the commonest etiology in both periods (50.0% and 51.1%). The proportion of patients prescribed oral/inhaled combination therapies increased from 47.8% to 57.5%. Oral/inhaled combination therapies were frequently prescribed to patients with congenital heart disease-related PAH (81.8%). There was no significant trend in prescribing practices based on French low-risk criteria: among patients with 0, 1, 2, 3, or 4 criteria, 53.8%, 68.8%, 52.8%, 66.7%, and 39.4% were prescribed oral/inhaled combination therapies, and 0%, 16.7%, 27.0%, 17.3%, and 15.2% were prescribed oral/inhaled monotherapies, respectively. Macitentan, tadalafil, selexipag, and epoprostenol were the most frequently prescribed drugs. The severity of PAH decreased over time in Japan. Oral/inhaled combination therapies were generally preferred. Physicians generally prescribed therapies after considering the patients’ hemodynamics and clinical severity.

Severe Pulmonary Artery Hypertension Due to Cardiovascular Beriberi in a 3-Year-Old Boy Successfully Treated with a Phosphodiesterase Type 5 Inhibitor

Severe Pulmonary Artery Hypertension Due to Cardiovascular Beriberi in a 3-Year-Old Boy Successfully Treated with a Phosphodiesterase Type 5 Inhibitor