Incidence Of Pulmonary Hypertension Research Articles

Incidence of pulmonary hypertension in COPD and its relation to inflammatory marker interleukin-1

BackgroundMany COPD patients present with severe PH defined by a pulmonary vascular resistance (PVR) > 5 WU as measured by right heart catheterization (RHC), and inflammation is thought to be contributing strongly to pulmonary vascular remodeling in COPD besides hypoxia. Interleukin-1 (IL-1) is thought to be a major cytokine that may be involved in development of PH in these patients.ObjectiveThis study aimed to identify the incidence of PH in COPD and its relation to inflammatory marker IL-1.Patients and methodsOne-hundred COPD patients underwent echocardiography and serum IL-1 analysis, and patients with high probability of PH underwent pulmonary artery catheterization using Swan-Ganz catheter.ResultsThe mean serum IL-1 level was 82 pg/ml ± 22 pg/ml (the normal IL-1 serum level is known to be 0:5 pg/mL), 51% of the participants were categorized as having a low probability of PH, 35% was intermediate, and 14% was high. RHC results were as follows: mild combined pre- and postcapillary PH was diagnosed in 14.3% of the patients. Mild precapillary PH was found in 42.9%, making it the most common type. Severe combined pre- and postcapillary PH was noted in 21.4% of the patients. Severe precapillary PH was present in 14.3%. A significant positive correlations were observed between serum IL-1 and tricuspid regurgitation velocity (TRV) (r = 0.409, P < 0.001), estimated systolic pulmonary artery pressure (ESPAP) (r = 0.508, P < 0.001), and mean pulmonary artery pressure (mPAP) (r = 0.410, P = 0.140).ConclusionSerum IL-1 is a potent predictor of a high probability of PH in COPD patients, and there was significant positive correlation between serum IL-1 and echocardiographic findings and PH probability and RHC findings in COPD patients.

Multicentre, randomised controlled trial of physiological-based cord clamping versus immediate cord clamping in infants with a congenital diaphragmatic hernia (PinC): statistical analysis plan

BackgroundInfants born with congenital diaphragmatic hernia (CDH) are at high risk of respiratory insufficiency and pulmonary hypertension. Routine practice includes immediate clamping of the umbilical cord and endotracheal intubation. Experimental animal studies suggest that clamping the umbilical cord guided by physiological changes and after the lungs have been aerated, named physiological-based cord clamping (PBCC), could enhance the fetal-to-neonatal transition in CDH. We describe the statistical analysis plan for the clinical trial evaluating the effects of PBCC versus immediate cord clamping on pulmonary hypertension in infants with CDH (PinC trial).DesignThe PinC trial is a multicentre, randomised controlled trial in infants with isolated left-sided CDH, born ≥ 35.0 weeks of gestation. The primary outcome is the incidence of pulmonary hypertension in the first 24 h after birth. Maternal outcomes include estimated maternal blood loss. Neonatal secondary outcomes include mortality before discharge, extracorporeal membrane oxygenation therapy, and number of days of mechanical ventilation. Infants are 1:1 randomised to either PBCC or immediate cord clamping using variable random permutated block sizes (4–8), stratified by treatment centre and estimated severity of pulmonary hypoplasia (i.e. mild/moderate/severe). At least 140 infants are needed to detect a relative reduction in pulmonary hypertension by one third, with 80% power and 0.05 significance level. A chi-square test will be used to evaluate the hypothesis that PBCC decreases the occurrence of pulmonary hypertension. This plan is written and submitted without knowledge of the collected data. The trial has been ethically approved.Trial registrationClinicalTrials.gov NCT04373902 (registered April 2020).

Real-world diagnostic landscape and incidence of pulmonary hypertension in adult congenital heart disease patients using administrative claims data in Japan

Background Although pulmonary hypertension (PH) and Eisenmenger’s syndrome (ES) are common complications in adult congenital heart disease (ACHD), the frequency of diagnostic tests and the incidence of PH/ES in patients with ACHD in Japanese clinical practice are unclear. Therefore, we sought to clarify the frequency of diagnostic tests and incidence of PH/ES in patients with ACHD using the Medical Data Vision (MDV) database, the largest anonymized database of diagnosis procedure combination hospitals in Japan. Methods We conducted a retrospective cohort study using the MDV database (April 2008 to December 2021) of patients with ACHD (International Classificaiton of Diseases, 10th revision codes: Q203-204, Q210-213, Q250) aged ≥15 years. The frequency of laboratory/clinical tests and the incidence of PH/ES were calculated. Subgroup analyses were performed for the periods 2008–2015 and 2016–2021. Results Overall, 28219 ACHD patients were extracted from the MDV database (females 56.3%, males 43.7%; mean ± standard deviation age 44.7 ± 23.5 years). The mean ± standard deviation follow-up period was 2.5 ± 2.7 years. The frequencies of electrocardiography, ultrasonography, brain natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP), right heart catheterization, and pulmonary function tests (DLCO) were 2149.8, 1054, 1233, 340, 40.0, and 6.0 per 1000 person-years, respectively. The incidence rate of PH/ES was 32.8 per 1000 person-years. The incidence rate of PH/ES increased from 24.6 to 46.7 per 1000 person-years from 2008–2015 to 2016–2021. Conclusion We have clarified the frequency of diagnostic tests related to PH/ES and the incidence of PH/ES in patients with ACHD in clinical practice in Japan, including non-specialist institutions for PH.

Ultrasound-Assisted, Catheter-Directed Thrombolysis for Acute Intermediate/High-Risk Pulmonary Embolism: Design of the Multicenter USAT IH-PE Registry and Preliminary Results.

Catheter-based revascularization procedures were developed as an alternative to systemic thrombolysis for patients with intermediate-high- and high-risk pulmonary embolisms. USAT IH-PE is a retrospective and prospective multicenter registry of such patients treated with ultrasound-facilitated, catheter-directed thrombolysis, whose preliminary results are presented in this study. The primary endpoint was the incidence of pulmonary hypertension (PH) at follow-up. Secondary endpoints were short- and mid-term changes in the echocardiographic parameters of right ventricle (RV) function, in-hospital and all-cause mortality, and procedure-related bleeding events. Between March 2018 and July 2023, 102 patients were included. The majority were at intermediate-high-risk PE (86%), were mostly female (57%), and had a mean age of 63.7 ± 14.5 years, and 28.4% had active cancer. Echocardiographic follow-up was available for 70 patients, and in only one, the diagnosis of PH was confirmed by right heart catheterization, resulting in an incidence of 1.43% (CI 95%, 0.036-7.7). RV echocardiographic parameters improved both at 24 h and at follow-up. In-hospital mortality was 3.9% (CI 95%, 1.08-9.74), while all-cause mortality was 11% (CI 95%, 5.4-19.2). Only 12% had bleeding complications, of whom 4.9% were BARC ≥ 3. Preliminary results from the USAT IH-PE registry showed a low incidence of PH, improvement in RV function, and a safe profile.

Abstract 12547: Incidence of Pulmonary Hypertension in the Echocardiographic Referral Population

Background: Incident rates (IRs) for pulmonary hypertension (PH) using diagnostic data rather than diagnostic codes (DC) have not been reported. We examined PH IRs, risk factors, and mortality among patients (pts) referred for echocardiography (TTE) in a national healthcare system and a separate tertiary care center. Methods: Pulmonary artery systolic pressure (PASP) estimates were extracted from the Veterans Affairs (1999-2020) and Vanderbilt (1994-2020) systems. PH was defined as PASP &gt;35 mmHg. Individuals free of PH at baseline were followed through incident PH, death, or censored at end of study. Secondary outcome was mortality rate (MR) after incident PH. We used Poisson regression to estimate IRs and cox models for hazard ratios. Results: We identified 245,067 veterans (60 years [IQR 55-64], 94% male, 20% Black) and 117,526 VUMC pts (60 years [IQR 46-70], 46% male, 11% Black) free of PH at baseline. Only 22% of pts with TTE-based PH had a DC for PH. PH IRs and adjusted hazard were substantially higher in pts with HF or COPD and highest in pts with both ( Table 1 ). MR after incident PH was highest in pts with both HF and COPD and lowest in pts without either (Figure 1A ). MRs increased markedly at PASP values &gt;45mmHg ( Figure 1B ). Independent risk factors for incident PH included older age (HR 1.07; 95%CI 1.06-1.09), male sex (HR 1.24; 95%CI 1.17-1.30), black race (HR 1.10; 95%CI 1.07-1.13), and cardiometabolic comorbidities. Conclusions: PH IRs estimated by raw diagnostic data are higher than DC-based IRs and strongly associated with HF and COPD. PASP &gt;45mmHg at the time of incident PH is associated with high mortality.

Outcomes of atrioventricular septal defects with and without down syndrome: analysis of the national inpatient database.

Controversial data exist about the impact of Down syndrome on outcomes after surgical repair of atrioventricular septal defect. (A) assess trends and outcomes of atrioventricular septal defect with and without Down syndrome and (B) determine risk factors associated with adverse outcomes after atrioventricular septal defect repair. We queried The National Inpatient Sample using International Classification of Disease codes for patients with atrioventricular septal defect < 1 year of age from 2000 to 2018. Patients' characteristics, co-morbidities, mortality, and healthcare utilisation were evaluated by comparing those with versus without Down syndrome. In total, 2,318,706 patients with CHD were examined; of them, 61,101 (2.6%) had atrioventricular septal defect. The incidence of hospitalisation in infants with atrioventricular septal defect ranged from 4.5 to 7.5% of all infants hospitalised with CHD per year. A total of 33,453 (54.7%) patients were associated with Down syndrome. Double outlet right ventricle, coarctation of the aorta, and tetralogy of Fallot were the most commonly associated with CHD in 6.9, 5.7, and 4.3% of patients, respectively. Overall atrioventricular septal defect mortality was 6.3%. Multivariate analysis revealed that prematurity, low birth weight, pulmonary hypertension, and heart block were associated with mortality. Down syndrome was associated with a higher incidence of pulmonary hypertension (4.3 versus 2.8%, p < 0.001), less arrhythmia (6.6 versus 11.2%, p < 0.001), shorter duration for mechanical ventilation, shorter hospital stay, and less perioperative mortality (2.4 versus 11.1%, p < 0.001). Trends in atrioventricular septal defect hospitalisation had been stable over time. Perioperative mortality in atrioventricular septal defect was associated with prematurity, low birth weight, pulmonary hypertension, heart block, acute kidney injury, and septicaemia. Down syndrome was present in more than half of atrioventricular septal defect patients and was associated with a higher incidence of pulmonary hypertension but less arrhythmia, lower mortality, shorter hospital stay, and less resource utilisation.

Pulmonary Hypertension in Patients of Chronic Kidney Disease on Maintenance Hemodialysis: Study from a Tertiary Care Center in Central India

To study the incidence of pulmonary hypertension (PH) in chronic kidney disease (CKD) stage V patients on maintenance hemodialysis (HD) at our center. To compare clinical and metabolic variables among CKD patients with and without PH to search for possible etiologic factors. Comparison of PH in CKD patients at baseline and after 3 months of sildenafil therapy. The study was conducted in the Department of Nephrology, Sri Aurob-indo Institute of Medical Sciences, Indore, for a period of 1 year from December 2021 to November 2022. All CKD patients on maintenance HD at our center were included in the study. A pre-structured proforma was used to record patient data. Detailed clinical examination, 2DECHO, and Biochemical tests were done. All patients with mean pulmonary artery pressure (mPAP) &gt; 25 mmHg on 2D echocardiography were considered to have PH and were started on sildenafil therapy 20 mg three times a day for 3 months. PH was classified as mild PH (mPAP &gt; 25 up to 40 mmHg), moderate PH (mPAP &gt; 40 mmHg to 60 mmHg), and severe PH (mPAP &gt; 60 mmHg). Patients were then followed for 3 months to look for episodes of dyspnea and emergency admissions and reassessed after 3 months by repeat 2D echocardiography to find improvement in PH. A total of 102 patients were analyzed during the study period; among them, 40 patients (39.2%) had PH. Out of them, 18 patients (45%) had mild PH, 14 patients (35%) had moderate PH, and 8 patients (20%) patients had severe PH. Average age of our patients was 48.8 ± 9.4 years, the majority being men. On comparing the clinical features between patients with and without PH, none of the clinical parameters had any statistically significant impact on PH. Also, none of the laboratory parameters had statistical significance among PH and non-PH groups. Among the patients with PH, 25 patients (62.5%) had Arteriovenous (AV) fistula, 10 patients (25%) had temporary dialysis catheters. Eight patients (20%) had jugular catheters, two patients (5%) had femoral catheters, and 5 (12.5%) patients had tunneled jugular catheters. Initially, 102 patients were enrolled in the study. Of these, 40 (39.2%) had PH and 62 (60.7%) did not. Patients who had PH started sildenafil 20 mg three times a day. Of these 40 patients, at 3 months, eight patients were lost to follow-up, and 32 patients with PH remained in the study. Emergency admissions in each group of PH declined after 3 months, and the result was statistically significant. Echocardiographic findings were compared in patients with PH and without PH, but the difference in patients on HD with PH and without PH was not statistically significant. PH is a significant problem in CKD patients on HD. This issue needs to be evaluated in a timely manner to avoid the risk of morbidity and mortality. It is vital to treat them at the earliest to prevent life-threatening complications.

Incident pulmonary hypertension in 13 488 cases investigated with repeat echocardiography: a clinical cohort study.

We addressed the paucity of data describing the characteristics and natural history of incident pulmonary hypertension. Adults (n=13 448) undergoing routine echocardiography without initial evidence of pulmonary hypertension (estimated right ventricular systolic pressure, eRVSP <30.0 mmHg) or left heart disease were studied. Incident pulmonary hypertension (eRVSP ≥30.0 mmHg) was detected on repeat echocardiogram a median of 4.1 years apart. Mortality was examined according to increasing eRVSP levels (30.0-39.9, 40.0-49.9 and ≥50.0 mmHg) indicative of mild-to-severe pulmonary hypertension. A total of 6169 men (45.9%, aged 61.4±16.7 years) and 7279 women (60.8±16.9 years) without evidence of pulmonary hypertension were identified (first echocardiogram). Subsequently, 5412 (40.2%) developed evidence of pulmonary hypertension, comprising 4125 (30.7%), 928 (6.9%) and 359 (2.7%) cases with an eRVSP of 30.0-39.9 mmHg, 40.0-49.9 mmHg and ≥50.0 mmHg, respectively (incidence 94.0 and 90.9 cases per 1000 men and women, respectively, per year). Median (interquartile range) eRVSP increased by +0.0 (-2.27 to +2.67) mmHg and +30.68 (+26.03 to +37.31) mmHg among those with eRVSP <30.0 mmHg versus ≥50.0 mmHg. During a median 8.1 years of follow-up, 2776 (20.6%) died from all causes. Compared to those with eRVSP <30.0 mmHg, the adjusted risk of all-cause mortality was 1.30-fold higher in 30.0-39.9 mmHg, 1.82-fold higher in 40.0-49.9 mmHg and 2.11-fold higher in ≥50.0 mmHg groups (all p<0.001). New-onset pulmonary hypertension, as indicated by elevated eRVSP, is a common finding among older patients without left heart disease followed-up with echocardiography. This phenomenon is associated with an increased morality risk even among those with mildly elevated eRVSP.

Analysis of the Imaging Features and Prognosis of Pulmonary Tuberculosis Complicated with Pulmonary Embolism

This study aimed to explore the imaging characteristics of patients with pulmonary tuberculosis complicated with pulmonary embolism and analyze the prognosis of the condition, thereby reducing the mortality and misdiagnosis rate of complications in this type of pulmonary tuberculosis. In this retrospective study, a total of 70 patients diagnosed with pulmonary embolism by computed tomography pulmonary angiography (CTPA) from January 2016 to May 2021 in Anhui Chest Hospital were included. Among them, 35 patients with pulmonary embolism combined with pulmonary tuberculosis were set as the study group, and the other 35 patients with pulmonary embolism only were set as the control group. The imaging findings of chest CT examination, the incidence of pulmonary hypertension, the level of N-terminal proto-B-type brain natriuretic peptide (NT-proBNP), and the prognosis of patients were compared between the two groups. The incidence of deep venous embolism was evaluated by ultrasonography of the lower extremity. In the study group, the median age of patients was 71 years, and the ratio of males to females was 2.5 to 1. In the control group, the median age was 66 years old, and the male-to-female ratio was 2.2 to 1. There were 16 cases (16/35, 45.71%) in the study group and 10 cases (10/35, 28.57%) in the control group with an increased level of NT-proBNP. Pulmonary hypertension occurred in 10 patients (10/35, 28.57%) in the study group and 7 patients (7/35, 20.00%) in the control group. Patients who lost follow-up included 5 in the study group (5/35, 14.29%) and 3 in the control group (3/35, 8.57%). There were 17 cases (17/35, 48.57%) in the study group and 3 cases (3/35, 8.57%) in the control group with pulmonary artery widening, and the difference was significant (P < 0.001). There were 13 deaths in the study group (13/35, 37.14%) and 1 death in the control group (1/35, 2.86%), and the difference was significant (P <0.001). Special signs of pulmonary artery widening, pulmonary hypertension of varying degrees, and increased levels of NT-proBNP of varying degrees can be found in patients with pulmonary tuberculosis complicated with pulmonary embolism, and the three signs are positively correlated. The mortality of patients with pulmonary tuberculosis complicated with pulmonary embolism is significantly higher than that of patients with pulmonary embolism alone. Pulmonary tuberculosis and pulmonary embolism both occur in the ipsilateral lung, causing clinical symptoms to cover each other, thereby making diagnosis difficult.

Study of pulmonary hypertension in post-COVID-19 patients by transthoracic echocardiography

BackgroundA devastating medical disorder, the coronavirus pandemic infection (COVID-19), produced by the coronavirus 2 (SARSCoV-2), is primarily characterized by severe pneumonia. Pulmonary hypertension (PH), which may cause right ventricular (RV) involvement and dysfunction, can occur as a result of lung parenchymal injury and disturbed pulmonary circulation. Transthoracic echocardiography (TTE) is a very reliable noninvasive approach to determining the severity of PH. Similar to that, thorax computer tomography (TCT) can effectively detect the severity of lung damage during the acute phase of a COVID-19 infection.AimsThe goal of this research is to examine PH and altered right ventricular function by TTE in post-COVID-19 cases.Patients and methodsThis retrospective case–control study was conducted at Tanta Chest University Hospital, Tanta, Egypt. The study started from October 2021 to September 2022 on 50 post-COVID-19 cases with one or more clinical manifestations of PH. These cases underwent TTE (group I showed normal PAP “control group,” groups II & III with PH further subdivided according to PaO2).ResultsRisk factors of age, BMI, diabetes mellitus, and smoking were substantially raised in group III, but sex and hypertension were insignificant. Symptoms of chest pain, dyspnea, and palpitation were worse in group III. Levels of LDH, d-dimer, ESR, and serum bilirubin were substantially increased in group III in comparison to the other groups. Post-COVID-19-associated lung fibrosis and embolism were higher in group III. Mean values of estimated systolic pulmonary artery pressure (esPAP) and right atrial and right ventricular diameters were substantially increased in groups III and II in comparison to group I. Mean values of RV-GLS and TAPSE were lower in groups III and II in comparison to group I. FEV1, FVC, PEFR, and FEF25–75% percentage of the predicted were significantly low in groups II and III. FEV1/FVC ratio was substantially lower in group II in comparison to groups I and III.ConclusionsThe incidence of pulmonary hypertension in post-COVID-19 patients with suspected manifestations of PH is 70%. Increased age, BMI, DM, smoking, decreased PaO2, increased CORADS score, and abnormal spirometry are risk factors for PH in post-COVID-19 patients. Patients with post-COVID-19 PH stay more either in ICU or ward.

Feasibility of a screening algorithm for chronic thromboembolic pulmonary hypertension: The OSIRIS study

IntroductionChronic thromboembolic pulmonary hypertension (CTEPH) is a long-term sequel to pulmonary embolism (PE) whose incidence varies according to different published studies. We have carried out this study to determine its incidence within 2 years after index pulmonary embolism and to study limitations to an early diagnosis. Material and methodsOSIRIS is a multicentre, longitudinal cohort study. Patients were followed for 3, 6, 12, and 24 months after pulmonary embolism using a structured three-step algorithm. A physician-centered questionnaire at least one positive response in a screening proceeded to the second step, transthoracic echocardiography. The third step consisted of ventilation/perfusion lung scintigraphy and right heart catheterisation. A transthoracic echocardiography was performed in patients without positive response in the screening questionnaire after 2 years. CTEPH diagnosis required haemodynamic confirmation by right heart catheterisation and mismatched perfusion defects on lung scintigraphy. ResultsA total of 1191 patients were enrolled in 18 Spanish hospitals. Cumulative CTEPH incidence after 2-years PE was: 2.49 % (95 % CI: 1.68–3.56) and the incidence rate of CTEPH was 1.1 cases per 1000 person-months (95 % CI: 0.725; 1.60). The CTEPH algorithm presented a lack of adherence of 29 %; patient and physician preferences posed barriers to the triage algorithm The screening questionnaire, in patients who completed the follow-up, shows a specificity of 91.3 % (89.0–93.2 %) and negative predictive value of 99.4 % (98.4–99.8 %).. ConclusionsOSIRIS provides practiced clinical based data on the chronic thromboembolic pulmonary hypertension incidence and identified barriers to the implementation of a 3-step triage algorithm for its detection. Clinical trial registrationclinicaltrials.gov identifier: NCT03134898.

Assessment of left atrial reservoir function in rheumatic mitral stenosis with pulmonary hypertension

The pathophysiology triggering dyspnea in rheumatic MS patients remains not fully understood. Recently introduced echocardiographic techniques allowed the study of left atrial reservoir function (LASr) notably in patients with PH. The objective of this study was to assess the correlation between LASr determined by 2D STE derived from global LA strain and PH. We performed prospective 2D TTE in patients with rheumatic MS. 2D and doppler TTE parameters, including indexed LA volume, maximal trans tricuspid velocity (TRVmax), mean trans-mitral gradient (MTMG), valve area (MVA) using pressure half time (PHT), 2D and 3D planimetry and left ventricular index stroke volume, were recorded. Doppler parameters are determined as the mean of three measurements. Maximal TRVmax was used as an indicator of the degree of PH to ignore assumptions on the right atrial pressure. A TRVmax cut-off value ≥ 2.9 m/s was retained to determine an intermediate to high probability of PH. NYHA functional status was determined moments before performing the scan. We enrolled 195 patients with rheumatic MS, with a mean age of 50.55 ± 12.07 years (between February 2018 and October 2021). Patients were divided into two groups: group 1 had TRVmax ≥ 2.9 m/s and group 2 had TRVmax < 2.9 m/s. There was no difference in age (52 ± 12 vs. 49 ± 11, P = 0.16) and in sex (respectively 69.8% and 76.1% were female, P = 0.3). AF was comparable between the two groups (69.8 vs. 65.7%, P = 0.5). There was no difference in the incidence of severe dyspnea (48.8% vs. 43.1%, P = 0.5 had NYHA class III or I symptoms). Incidence of diabetes mellitus was significantly higher among patients with PH (24.4 vs. 10.6%, P = 0.02). Patients in the PH group had significantly higher MTMG (13 ± 6 vs. 8 ± 3 mmHg, P < 0.001) and significantly lower MVA (1.1 ± 0.5 vs. 1.5 ± 0.5 cm2, P < 0.001). LASr was significantly higher in patients without PH (11.1 ± 7 vs. 8.9 ± 5%, P = 0.05). LASr was associated with a lower incidence of pulmonary hypertension in patients with MS.

Cardiovascular Evaluation in Patients with Systemic Sclerosis in the Turkish Population

Cardiac involvement in systemic sclerosis (SSc) can lead to high morbidity and mortality. Therefore, early diagnosis and treatment are required. The aim of this study was to investigate the clinical, laboratory, and echocardiographic features of SSc, evaluate the proportion of patients with cardiovascular disease, and compare them with other population-based studies in the Turkish population. This study included 150 patients who were previously diagnosed and treated in the rheumatology clinic. Their age, sex, clinical signs and symptoms, laboratory and echocardiography findings, and concomitant diseases were evaluated. The results showed that the disease duration was &lt;1 year and, at most, 11 years, with only one patient having elevated pulmonary artery pressure. In addition, patients with SSc in our region had similar demographic, clinical, laboratory, and echocardiographic features with those in other countries. This study demonstrated that hypertension is positively correlated with disease duration and the incidence of pulmonary hypertension is very low in patients with SSc.

Analysis of clinical features between active and inactive patients of Takayasu's arteritis with pulmonary arteries involvement

BackgroundThe aim of this study was to investigate the clinical characteristics of patients between active and inactive Takayasu's arteritis with pulmonary artery involvement (PTA) and to identify better markers of disease activity in these patients. MethodsSixty-four PTA patients in Beijing Chao-yang hospital (2011 to 2021) were included. According to National Institutes of Health criteria, 29 patients were in active stage and 35 were in inactive stage. Their medical records were collected and analyzed. ResultsCompared with inactive group, patients in active group were younger. More patients in active stage presented fever (41.38% vs 5.71%), chest pain (55.17% vs 20%), increased C-reactive protein (2.91 vs 0.46 mg/L), erythrocyte sedimentation rate (35.0 vs 9 mm/h), and platelet count (291 vs 221 × 109/L). Pulmonary artery wall thickening was more common in active group (51.72% vs 11.43%). These parameters were restored after treatment. The incidence of pulmonary hypertension was comparable between groups (34.48% vs 51.43%), but patients in active group had lower pulmonary vascular resistance (PVR) (361.0 vs 891.0 dyn·s·cm−5) and higher cardiac index (2.76 ± 0.72 vs 2.01 ± 0.58 L/min/m2). On multivariate logistic regression analysis, chest pain [odds ratio (OR) 9.37, 95%CI (1.98–44.38), P = 0.005], increased platelet count (>242.5 × 109/L) [OR 9.03, 95%CI (2.10–38.87), P = 0.003] and pulmonary artery wall thickening [OR 7.08, 95%CI (1.44–34.89), P = 0.016] were independently associated with disease activity. ConclusionChest pain, increased platelet count, and pulmonary artery wall thickening are potential new indicators of disease activity in PTA. Patients in active stage may have lower PVR and better right heart function.

Patent ductus arteriosus and the risk of bronchopulmonary dysplasia-associated pulmonary hypertension.

The aim of the study was to determine whether prolonged exposure to a moderate/large patent ductus arteriosus left-to-right shunt (PDA) increases the risk of late (beyond 36 weeks) pulmonary hypertension (BPD-PH) and pulmonary vascular disease (BPD-PVD) during the neonatal hospitalization in preterm infants (<28 weeks' gestation) with bronchopulmonary dysplasia (BPD). All infants requiring respiratory support ≥36 weeks had systematic echocardiographic evaluations for BPD-PH at planned intervals. Infants were classified as having either flow-associated BPD-PH (BPD-flow-PH) or BPD-PVD. 256 infants survived ≥36 weeks: 105 had NO BPD (were off respiratory support by 36 weeks); 151 had BPD. 22/151 had BPD-PH (12/22 had BPD-flow-PH from a PDA that persisted beyond 36 weeks; 10/22 had BPD-PVD). Moderate/large PDA shunts that persisted beyond 36 weeks were significantly associated with an increased incidence of BPD-PH due to BPD-flow-PH. We found no association between the duration of PDA exposure and the incidence of BPD-PVD. Moderate/large PDA shunts increase the risk of flow-associated BPD-PH when present beyond 36 weeks. Although term infants with PDA-congenital heart disease can develop pulmonary vascular remodeling and PVD after months of PDA exposure, we found no echocardiographic evidence in preterm infants that prolonged PDA exposure increases the incidence of BPD-PVD during the neonatal hospitalization. In our study, preterm infants (<28 weeks' gestation) with bronchopulmonary dysplasia (BPD) had a 15% incidence of pulmonary hypertension (PH) beyond 36 weeks' postmenstrual age as a comorbidity. Moderate/large patent ductus arteriosus (PDA) shunts increased the risk of flow-associated PH when present beyond 36 weeks. Although months of prolonged PDA exposure can cause pulmonary vascular remodeling and pulmonary vascular disease (PVD) in term infants with PDA-congenital heart disease, we found no echocardiographic evidence for an association between the duration of PDA exposure and the incidence of late PVD during the neonatal hospitalization in preterm infants with BPD.

Intersticijumske bolesti pluća i sekundarna plućna hipertenzija

Interstitial lung disease alone can have a poor prognosis, and when associated with pulmonary hypertension there is a significant reduction in survival rates. Since the incidence of pulmonary hypertension in patients with interstitial lung diseases is very high and the symptoms are similar and often unrecognized, our aim is to point out the significance of both coexisting diseases and to prompt clinicians to suspect pulmonary hypertension. Through a brief review of the pathohistological changes, diagnostic methods, and the clinical presentation of these diseases, the similarities and differences that can help in the management of these patients, are shown. The latest treatment guidelines, with a special focus on the impact of antifibrotic treatment (nintedanib and pirfenidone) on pulmonary hypertension, are presented.

Respiratory support strategies in the management of severe, longstanding bronchopulmonary dysplasia.

Despite efforts to minimize ventilator-induced lung injury, some preterm infants require positive pressure support after 36 weeks' post-menstrual age. Infants with severe BPD typically experience progressive mismatch of ventilation and perfusion, which manifests as respiratory distress, hypoxemia in room air, hypercarbia, and growth failure. Lung compliance varies, but lung resistance generally increases with prolonged exposure to positive pressure ventilation and other sources of inflammation. Serial lung radiographs reveal a heterogeneous pattern, with areas of both hyperinflation and atelectasis; in extreme cases, macrocystic changes may be noted. Efforts to wean the respiratory support are often unsuccessful, and trials of high frequency ventilation, exogenous corticosteroids, and diuretics are common. The incidence of pulmonary hypertension increases with the severity of BPD, as does the mortality rate. Therefore, periodic screening and efforts to mitigate the risk of PH is fundamental to the management of longstanding BPD. Failure of conventional, lung-protective strategies (e.g., high rate/low tidal-volume and/or high frequency ventilation) warrants consideration of ventilatory strategies individualized to the disease physiology. Non-invasive modes of respiratory support may be successful in infants with mild to moderate BPD phenotypes. However, infants with moderate to severe BPD phenotypes often require invasive respiratory support, and pressure-limited or volume-targeted conventional ventilation may be better suited to the physiology than high-frequency ventilation. The consistent provision of adequate support is fundamental to the management of longstanding BPD and is best achieved with a stepwise increase in ventilator support until comfortable spontaneous respirations are achieved. Adequately supported infants typically experience improvements in both oxygenation and ventilation, which, if sustained, may arrest and generally reverses the course of a potentially lethal lung disease. Care should be individualized to address the most likely pulmonary mechanics, including variable lung compliance, elevated airway resistance, and variable airway obstruction.

Incident pulmonary hypertension in 13,448 cases investigated with repeat echocardiography: insight from the National Echo Database of Australia (NEDA)

Abstract Background We addressed the paucity of data describing the characteristics and natural history of incident pulmonary hypertension (PHT). Methods In this observational clinical cohort study, we examined 85,173 individuals undergoing routine echocardiography for heart disease without evidence of PHT (according to estimated right ventricular systolic pressure, eRVSP &amp;lt;30 mmHg). Subsequent age and sex-specific incidence of PHT were derived from repeat echocardiograms conducted a median of 3.43 (interquartile range, IQR 1.49 to 6.55) years apart in 13,448 adults. Progressive PHT severity with individual data linkage to all-cause mortality were examined per PHT stage: eRVSP 30–39 mmHg (mild PHT), 40–49 mmHg (moderate PHT) and ≥50 mmHg (severe PHT). Results A total of 6,169 men (45.9%, mean age 61.4±16.7 years) and 7,279 women (60.8±16.9 years) with no initial evidence of PHT were identified (first echocardiogram). Subsequently, 5,412 (40.2%,) developed PHT (repeat echocardiogram) – comprising 4,125 (30.7%, 65.0±14.3 years), 928 (6.9%, 69.2±13.5 years), and 359 (2.7%, 69.8±12.7 years) cases of mild, moderate, and severe PHT, respectively. The incidence of all stages of PHT was 15.2 cases per million men/annum and 12.5 cases per million women/annum. Overall, median eRVSP increased by +7.4 (IQR +4.6 to +10.1) and +30.7 (IQR +26.0 to +37.3) mmHg; median E:e' ratio increased by +1.0 (IQR −0.4 to +3.2) and +3.6 (IQR +2.0 to +8.2); and median LA volume increased by +5.0 (IQR +0.0 to +12.0) and +19.5 (IQR +9.0 to +31.0) ml/m2, respectively, in mild and severe PHT groups between first and last echocardiograms. During subsequent median 8.1 years follow-up, 2,776/13,448 (20.6%) individuals died from all-cause. Compared to no PHT, the age- and sex-adjusted hazard ratios for all-cause mortality increased to 1.35 (95% confidence interval, CI 1.23–1.47) in mild PHT, 1.94 (95% CI 1.73–2.18) in moderate PHT, and 2.43 (95% CI 2.09–2.83) in severe PHT (all p&amp;lt;0.001). Conclusions New onset of PHT is a common finding among individuals with heart disease followed-up with echocardiography. Even milder stage of PHT is associated with higher mortality, reinforcing the need for proactive evaluation for symptoms consistent with PHT. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Johnson &amp; Johnson: Investigator-initiated grant

Furthering the clinical development of navicixizumab in advanced epithelial ovarian cancer patients with a population pharmacokinetic model and exploratory exposure-safety-efficacy response analyses (225)

Objectives: Cumulative data from navicixizumab clinical trials were analyzed to establish a population pharmacokinetic model, which was further used to characterize the relationships of navicixizumab exposure with safety and efficacy parameters. Methods: A population pharmacokinetic model was developed using data from clinical trials with navicixizumab in advanced cancer patients (B83-001), in combination with paclitaxel in advanced ovarian cancer patients (B83-002) and combination with standard of care in colorectal cancer patients (B83-003). Exposure-safety analyses focused on the relationship between navicixizumab exposures and systemic hypertension as measured with mean arterial pressure data and incidence of pulmonary hypertension assessed using peak tricuspid velocity data. For the purposes of this analysis, pulmonary hypertension was defined as peak tricuspid velocities >3.4 m/s. Exposure-efficacy analyses focused on objective response rates collected using RECIST version 1.1 and sum of the longest diameters of the target lesion. Results: The overall pharmacokinetic profile of navicixizumab was best described by a 2-compartment model with dose-proportional pharmacokinetics observed at doses ≥ 2.5 mg/kg. The effects of patient weight and patient antidrug antibody (ADA) status were identified as significant covariates in the model, where ADA positivity was associated with reduced clearance values. Changes in mean arterial pressure were concentration-dependent, where both Stage III/IV and ADA positive patients had lesser changes in mean arterial pressures. While peak tricuspid velocities were not related to navicixizumab concentrations, dose, disease stage, or disease indication, pulmonary hypertension was observed as being related to cumulative navicixizumab exposures as measured by AUC and total dose. Navicixizumab exposures were not significantly related to objective response rates. Ovarian stage III/IV cancer patients demonstrated a significant relationship between higher exposure and significantly greater reductions in target tumor size. Conclusions: A robust pharmacokinetic model was developed, demonstrating linear navicixizumab pharmacokinetics at doses ≥ 2.5 mg/kg. While the impact of ADA on navicixizumab clearance was statistically significant, the impact at therapeutically relevant doses was not clinically meaningful. Changes in mean arterial pressures with navicixizumab concentrations support a favorable adverse event profile in the ovarian patient population, while cumulative dose and exposures are associated with peak tricuspid velocities ≥ 3.4 m/s. When both ORR and changes in target tumor size were considered, cumulative navicixizumab exposures were associated with increased efficacy in ovarian cancer patients. Cumulative data reported herein support continued clinical development of navicixizumab, especially in ovarian cancer patients. Objectives: Cumulative data from navicixizumab clinical trials were analyzed to establish a population pharmacokinetic model, which was further used to characterize the relationships of navicixizumab exposure with safety and efficacy parameters. Methods: A population pharmacokinetic model was developed using data from clinical trials with navicixizumab in advanced cancer patients (B83-001), in combination with paclitaxel in advanced ovarian cancer patients (B83-002) and combination with standard of care in colorectal cancer patients (B83-003). Exposure-safety analyses focused on the relationship between navicixizumab exposures and systemic hypertension as measured with mean arterial pressure data and incidence of pulmonary hypertension assessed using peak tricuspid velocity data. For the purposes of this analysis, pulmonary hypertension was defined as peak tricuspid velocities >3.4 m/s. Exposure-efficacy analyses focused on objective response rates collected using RECIST version 1.1 and sum of the longest diameters of the target lesion. Results: The overall pharmacokinetic profile of navicixizumab was best described by a 2-compartment model with dose-proportional pharmacokinetics observed at doses ≥ 2.5 mg/kg. The effects of patient weight and patient antidrug antibody (ADA) status were identified as significant covariates in the model, where ADA positivity was associated with reduced clearance values. Changes in mean arterial pressure were concentration-dependent, where both Stage III/IV and ADA positive patients had lesser changes in mean arterial pressures. While peak tricuspid velocities were not related to navicixizumab concentrations, dose, disease stage, or disease indication, pulmonary hypertension was observed as being related to cumulative navicixizumab exposures as measured by AUC and total dose. Navicixizumab exposures were not significantly related to objective response rates. Ovarian stage III/IV cancer patients demonstrated a significant relationship between higher exposure and significantly greater reductions in target tumor size. Conclusions: A robust pharmacokinetic model was developed, demonstrating linear navicixizumab pharmacokinetics at doses ≥ 2.5 mg/kg. While the impact of ADA on navicixizumab clearance was statistically significant, the impact at therapeutically relevant doses was not clinically meaningful. Changes in mean arterial pressures with navicixizumab concentrations support a favorable adverse event profile in the ovarian patient population, while cumulative dose and exposures are associated with peak tricuspid velocities ≥ 3.4 m/s. When both ORR and changes in target tumor size were considered, cumulative navicixizumab exposures were associated with increased efficacy in ovarian cancer patients. Cumulative data reported herein support continued clinical development of navicixizumab, especially in ovarian cancer patients.

Surgical and Cardiac Catheterization Outcomes of Scimitar Syndrome Patients: A Three Decade Single-Center Experience.

Scimitar syndrome (SS) is a rare congenital condition which includes partial anomalous pulmonary venous return (PAPVR) and a variable degree of pulmonary hypoplasia. We describe the clinical features, therapeutic approach and outcomes of patients who underwent cardiac catheterization and/or surgical repair of the scimitar vein at a single institutionin the United States. This retrospective cohort study included all patients with SS who underwent scimitar vein surgical repair or cardiac catheterization from October 1989 through August 2021 in a tertiary care center. A total of 84 patients with SS were included and median follow-up time was 74months. Patients diagnosed with SS under the age of one year had a significantly greater incidence of congenital heart defects (CHD) (p < 0.001), non-cardiac anomalies (p = 0.02), pulmonary hypertension (p = 0.02), and mortality (p = 0.04) compared to those diagnosed over the age of 1year. Twenty-eight patients underwent surgical repair of the scimitar vein. Overall, eight (10%) patients died. Compared to surviving patients, deceased patients had a significantly higher incidence of pulmonary hypertension (PH), neonatal SS diagnosis, and extracorporeal membrane oxygenation (ECMO) support. Median scimitar vein pressure (20mmHg) of deceased patients was significantly higher compared to pressures in surviving patients (11mmHg; p = 0.02). PH, CHD, neonatal SS diagnosis, ECMO support, and markedly elevated scimitar vein pressure are associated with mortality. Scimitar vein surgical repair during infancy is commonly associated with PH and restenosis that requires re-intervention.