Considerations in the Diagnosis and Management of Pulmonary Hypertension Associated With Left Heart Disease.

Pulmonary hypertension associated with left heart disease (PH-LHD) remains the most common cause of pulmonary hypertension globally. Etiologies include heart failure with reduced and preserved ejection fraction and left-sided valvular heart diseases. Despite the increasing prevalence of PH-LHD, there remains a paucity of knowledge about the hemodynamic definition, diagnosis, treatment modalities, and prognosis among clinicians. Moreover, clinical trials have produced mixed results on the usefulness of pulmonary vasodilator therapies for PH-LHD. In this expert review, we have outlined the critical role of meticulous hemodynamic evaluation and provocative testing for cases of diagnostic uncertainty. Therapeutic strategies-pharmacologic, device-based, and surgical therapies used for managing PH-LHD-are also outlined. PH-LHD in advanced heart failure, and the role of mechanical circulatory support in PH-LHD is briefly explored. An in-depth understanding of PH-LHD by all clinicians is needed for improved recognition and outcomes among patients with PH-LHD.

Haemodynamic contributors to pulmonary hypertension across the spectrum of adult congenital heart disease.

AIMS: Adult congenital heart disease (ACHD) includes multiple disease states that predispose to pulmonary hypertension (PH). Haemodynamically, PH depends on abnormalities in three components: pulmonary blood flow (Qp), pulmonary vascular resistance (PVR) and pulmonary venous pressure (PVP). We sought to evaluate the prevalence and prognostic impact of individual haemodynamic abnormalities in ACHD. METHODS AND RESULTS: Retrospective study of ACHD patients undergoing cardiac catheterization at Mayo Clinic between 1999 and 2022 who were followed for the combined endpoint of death/heart transplantation. Among 1005 patients, 37% had mean pulmonary artery pressure (mPAP) ≥25 mmHg with more systemic ventricular disease, cyanotic disease and shunt lesions, highest N-terminal pro-B-type natriuretic peptide and worse right heart remodelling/dysfunction. Among those with biventricular circulation, elevated PVP, PVR and mPAP were associated with prognosis, but not increased Qp >8 L/min. However, risk of death/transplant increased for PVR only at ≥3 Wood units (hazard ratio [HR] 3.00, 95% confidence interval [CI] 2.17-4.15; p < 0.0001) and for mPAP only at ≥25 mmHg (HR 3.15, 95% CI 2.17-4.58; p < 0.0001), not at current recommended lower cutpoints. Combined abnormalities in PVP and PVR were associated with worst outcome (HR 5.20, 95% CI 3.55-7.63; p < 0.0001) with intermediate risk with either abnormality (HR 2.11, 95% CI 1.46-3.04; p < 0.0001). Findings were consistent across type of biventricular ACHD. Only with the Fontan (univentricular) circulation was a lower mPAP threshold (20 mmHg) associated with adverse outcomes. CONCLUSIONS: Elevation of mPAP ≥25 mmHg in ACHD with a biventricular circulation is prognostically important regardless of disease phenotype, but milder PH of 21-25 mmHg is not associated with adverse outcome unless associated with Fontan circulation. Elevation in PVP >15 mmHg and PVR ≥3 Wood units were each individually associated with mortality with combined abnormalities associated with greatest risk. Categorizing PH in ACHD by haemodynamic mechanism (PVR, PVP or Qp) allows meaningful prognostication, and may allow more unified study of targeted therapies across heterogeneous disease states in ACHD.

Riociguat as bridging therapy to pulmonary endarterectomy in patients with chronic thromboembolic pulmonary hypertension: a retrospective cohort study.

Background: In operable chronic thromboembolic pulmonary hypertension (CTEPH) patients, the utilization of bridging therapy with targeted medications prior to pulmonary endarterectomy (PEA) remains a topic of controversy, despite being common in cases of severe hemodynamic impairment. This study aims to assess the impact of riociguat as a bridging therapy on postoperative hemodynamics and outcomes. Methods: We conducted a retrospective study involving patients undergoing PEA from December 2016 to November 2023. Patients were categorized into two groups based on the use of riociguat before PEA. Pulmonary vascular resistance (PVR) following riociguat administration was assessed pre-PEA. Postoperative outcomes, including mortality, complications, and hemodynamics, were compared, employing propensity score matching analysis. Results: Among the patients, 41.8% (n=56) received riociguat as bridging therapy. In patients with PVR ≥800 dynes·sec·cm-5, riociguat resulted in a reduction in PVR {1,207 [974-1,698] vs. 1,125 [928-1,486] dynes·sec·cm-5, P<0.01}, while no significant difference was observed in patients with PVR <800 dynes·sec·cm-5 {641 [474-740] vs. 600 [480-768] dynes·sec·cm-5, P=0.46}. After propensity score matching, each group included 26 patients. The overall perioperative mortality rate was 2.6%. Postoperative PVR {326 [254-398] vs. 361 [290-445] dynes·sec·cm-5, P=0.35} was similar in the riociguat group compared to the control group. The incidence of residual pulmonary hypertension (PH) and other postoperative outcomes were also comparable. Conclusions: The use of riociguat as bridging therapy demonstrated hemodynamic improvement before PEA in patients with high preoperative PVR. However, no additional benefits in postoperative mortality or hemodynamics were observed.

Novel Staged Device Occlusion of Portosystemic Shunt With Atrial Flow Regulator in IVC Stent Platform.

We present the cases of 2 children diagnosed with extrahepatic portosystemic shunts, a very rare vascular anomaly, on investigation of cardiac symptomatology. Poorly developed portal venous systems necessitated staged shunt occlusion. This was achieved using atrial flow regulator devices positioned in an inferior vena cava stent platform performed in the cardiac catheterization laboratory.

Group 5 Pulmonary Hypertension Associated With T-Cell Large Granular Lymphocytic Leukemia: Hemodynamics and Treatment.

Group 5 pulmonary hypertension (PH) encompasses diverse diseases, with a few cases linking it to T-cell large granular lymphocytic (LGL) leukemia. We report a case of a 76-year-old woman, diagnosed with LGL leukemia and concomitant PH, treated with oral triple pulmonary arterial hypertension (PAH) therapy. She initially presented with dyspnea on exertion; evaluation revealed severe precapillary PH. Implementing cyclophosphamide for leukemia along with tadalafil and macitentan for PH led to sustained symptomatic and hemodynamic improvement for over 3 years. At that time, deterioration in PH prompted the addition of selexipag, resulting in sustained clinical improvement for an additional 5 years. This case exemplifies the potential for sustained benefits of PAH therapy in leukemia-associated PH and highlights the need for continued research on the mechanistic relationship between LGL leukemia and PH, with the hope of identifying new management strategies.

Mortality Risk Assessment Using the REVEAL 2.0 Score in Pulmonary Hypertension Secondary to Left Heart Disease.

Background: Pulmonary hypertension (PH) frequently complicates the course of patients with left heart disease (PH-LHD) and is associated with worse clinical outcomes. Mortality calculators for PH-LHD are lacking, and it is unclear whether any risk prediction tools originally derived from other forms of PH can accurately predict outcomes in patients with PH-LHD. Methods: We retrospectively analyzed data from 161 patients diagnosed with PH-LHD referred to our pulmonary hypertension center from 2016 to 2022. We calculated the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL 2.0) risk score and categorized patients as low, intermediate, or high-risk. We assessed survival at 1 and 3 years using Kaplan-Meier and Cox proportional hazards, as well as classification performance using a concordance index. Results: At the first outpatient visit, 15% of patients were stratified as low-risk, 27% as intermediate, and 57% as high-risk. Cumulative 1-year survival rates were 100%, 94%, and 91% for the low, intermediate, and high-risk strata, respectively. Cumulative 3-year survival rates were 96%, 89%, and 70% for the low, intermediate, and high-risk strata, respectively. We found no difference in outcomes at 1 year between risk groups. High-risk patients had an increased risk of death at 3 years using REVEAL 2.0 (HR 5.32, p < 0.001). However, while REVEAL 2.0 accurately discriminated high-risk patients, the hazard ratio was not statistically different between patients classified as intermediate-risk compared to low-risk. Conclusion: REVEAL 2.0 accurately predicted 3-year survival in PH-LHD patients with high-risk features. However, the mortality risk between patients classified as intermediate-risk was not different from the low-risk stratum, suggesting inaccurate classification for this group of patients.

Risk Factors and Mortality in Newborns with Persistent Pulmonary Hypertension: A Six-Year Single-Center Experience.

Objectives: Persistent pulmonary hypertension (PPHT) of the newborn is a disorder of circulatory transition resulting in high pulmonary vascular resistance with extrapulmonary right-to-left shunts causing hypoxemia. In this study, our aim was to evaluate the risk factors, administered treatments, and mortality of patients followed in our neonatal intensive care unit (NICU) due to PPHT over the past six years. Methods: Patients diagnosed with PPHT and followed in the NICU between January 2017 and November 2022 were included in the study. The sociodemographic characteristics, diagnoses that could lead to pulmonary hypertension, the presence of congenital anomalies, the duration of respiratory support treatment and hospital follow-up, treatments administered for PPHT, and mortality rates were evaluated. Results: Out of 21 patients diagnosed with persistent pulmonary hypertension, 9 of them (42.9%) were male. The mean gestational age of the patients was 37.6±3.7 weeks, and their birth weight was 3006±819grams. The APGAR scores at 1 and 5 minutes were 4(2-7) and 6(3-8), respectively. Risk factors during the antenatal period included fetal distress (38.1%), oligohydramnios (23.8%), intrauterine growth restriction (23.8%), gestational diabetes (14.3%), preeclampsia (4.8%), and chorioamnionitis (4.8%). The median duration of invasive mechanical ventilation for cases requiring respiratory support was 20.1 days, while the median duration of non-invasive ventilation was 3.7 days. Patients with a diagnosis of persistent pulmonary hypertension were treated with inhaled nitric oxide (iNO) in 76.2% of cases, milrinone in 66.7% of cases, sildenafil in 52.4% of cases, and iloprost in 14.3% of cases. The length of hospital stay for patients was 38.4 days, and 9 (42.9%) patients died. The patients who died had severe PPHT along with fetal inflammatory response syndrome (FIRS), congenital heart disease, pulmonary hypoplasia, pneumothorax, hypoxic-ischemic encephalopathy (HIE), and congenital anomalies. Conclusion: Persistent pulmonary hypertension, characterized by severe hypoxemia, is a neonatal emergency that necessitates early intervention, effective treatment of the underlying cause to prevent potential short-term and long-term morbidities and mortality. Effective treatment of the underlying cause in patients diagnosed with PPHT could reduce morbidity and mortality. It is inevitable to avoid the loss of patients with major abnormalities, severe comorbidities, and unpreventable organ dysfunctions.

Treatment and management of chronic thromboembolic pulmonary hypertension (CTEPH): A global cross-sectional scientific survey (CLARITY).

Advances in the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) over the past decade changed the disease landscape, yet global insight on clinical practices remains limited. The CTEPH global cross-sectional scientific survey (CLARITY) aimed to gather information on the current diagnosis, treatment, and management of CTEPH and to identify unmet medical needs. This paper focuses on the treatment and management of CTEPH patients. The survey was circulated to hospital-based medical specialists through Scientific Societies and other medical organizations from September 2021 to May 2022. The majority of the 212 respondents involved in the treatment of CTEPH were from centers performing up to 50 pulmonary endarterectomy (PEA) and/or balloon pulmonary angioplasty (BPA) procedures per year. Variation was observed in the reported proportion of patients deemed eligible for PEA/BPA, as well as those that underwent the procedures, including multimodal treatment and subsequent follow-up practices. Prescription of pulmonary arterial hypertension-specific therapy was reported for a variable proportion of patients in the preoperative setting and in most nonoperable patients. Reported use of vitamin K antagonists and direct oral anticoagulants was similar (86% vs. 82%) but driven by different factors. This study presents heterogeneity in treatment approaches for CTEPH, which may be attributed to center-specific experience and region-specific barriers to care, highlighting the need for new clinical and cohort studies, comprehensive clinical guidelines, and continued education.

Myo-inositol trispyrophosphate prevents right ventricular failure and improves survival in monocrotaline-induced pulmonary hypertension in the rat.

BACKGROUND AND PURPOSE: Pulmonary hypertension (PH) results from pulmonary vasculopathy, initially leading to a compensatory right ventricular (RV) hypertrophy, and eventually to RV failure. Hypoxia can trigger both pulmonary vasculopathy and RV failure. Therefore, we tested if myo-inositol trispyrophosphate (ITPP), which facilitates oxygen dissociation from haemoglobin, can relieve pulmonary vasculopathy and RV hypoxia, and eventually prevent RV failure and mortality in the rat model of monocrotaline-induced PH. EXPERIMENTAL APPROACH: Rats were injected with monocrotaline (PH) or saline (control) and received ITPP or placebo for 5 weeks. Serial echocardiograms were obtained to monitor the disease, pressure-volume loops were recorded and evaluated, myocardial pO2 was measured using a fluorescent probe, and histological and molecular analyses were conducted at the conclusion of the experiment. KEY RESULTS AND CONCLUSIONS: ITPP reduced PH-related mortality. It had no effect on progressive increase in pulmonary vascular resistance, yet significantly relieved intramyocardial RV hypoxia, which was associated with improvement of RV function and reduction of RV wall stress. ITPP also tended to prevent increased hypoxia inducible factor-1α expression in RV cardiac myocytes but did not affect RV capillary density. IMPLICATIONS: Our study suggests that strategies aimed at increasing oxygen delivery to hypoxic RV in PH could potentially be used as adjuncts to other therapies that target pulmonary vessels, thus increasing the ability of the RV to withstand increased afterload and reducing mortality. ITPP may be one such potential therapy.

A systematic review of the impact of pulmonary thromboendarterectomy on health-related quality of life.

Pulmonary thromboendarterectomy (PTE) is the current gold standard treatment for chronic thromboembolic pulmonary hypertension (CTEPH) and is a viable treatment option for chronic thromboembolic pulmonary disease (CTEPD). The progressive nature of both diseases severely impacts health-related quality of life (HRQoL) across a variety of domains. This systematic review was performed to evaluate the impact of PTE on short- and long-term HRQoL. A literature search was conducted on PubMed for studies matching the eligibility criteria between January 2000 and September 2022. OVID (MEDLINE), Google Scholar, EBSCOhost (EMBASE), and bibliographies of included studies were reviewed. Inclusion of studies was based on predetermined eligibility criteria. Quality appraisal and data tabulation were performed using predetermined forms. Results were synthesized by narrative review. The structure of this systematic review follows the PRISMA guidelines. This systematic review was prospectively registered in the PROSPERO register (CRD42022342144). Thirteen studies (2184 patients) were included. Within 3 months post-PTE, HRQoL improved in both CTEPD and CTEPH as measured by disease-specific and generic questionnaires. HRQoL improvements were sustained up to 5 years postoperatively in patients with CTEPH post-PTE. PTE remains the gold standard for treating CTEPH and improving HRQoL. Residual pulmonary hypertension and comorbidities such as COPD and coronary artery disease decrement HRQoL over time. The impact of mPAP and PVR on HRQoL outcomes postoperatively remain ambiguous. Pulmonary thromboendarterectomy remains the gold standard for treating CTEPH and has shown to improve HRQoL outcomes at 3-month sustaining improvements up to 5-year postoperatively. Residual pulmonary hypertension and comorbidities hinder HRQoL outcomes post-PTE.

Balloon pulmonary angioplasty for chronic thromboembolic pulmonary disease without pulmonary hypertension.

Balloon pulmonary angioplasty (BPA) is beneficial for patients with chronic thromboembolic pulmonary disease (CTEPD) with pulmonary hypertension (PH). However, the clinical benefit of BPA for the patients with CTEPD without PH remains unknown. In this study, we aimed to evaluate the efficacy, safety, and long-term outcomes of BPA in patients with CTEPD without PH. We retrospectively analyzed the data from 84 CTEPD patients with mean pulmonary artery pressure (mPAP) < 25 mmHg and 39 CTEPD patients with mPAP ≤ 20 mmHg (without PH). Among the 39 patients with CTEPD without PH, 14 underwent BPA (BPA-treated group), and the remaining 25 received no treatment (untreated group). In the patients with CTEPD without PH, BPA led to improvements in symptoms, pulmonary vascular resistance (3.6 ± 1.6 to 2.6 ± 1.1 Wood units, p < 0.001), peak oxygen consumption (16.1 ± 4.0 to 18.8 ± 4.3 mL/kg/min, p = 0.033), minute ventilation versus carbon dioxide production slope (41.4 ± 12.2 to 35.1 ± 6.7, p = 0.026), and mPAP/cardiac output slope (7.0 ± 2.6 to 4.4 ± 2.0 mmHg/L/min, p = 0.004) and facilitated the discontinuation of home oxygenation therapy, with no serious complications. Kaplan-Meier analysis showed no significant difference in all-cause mortality between the untreated and BPA-treated groups. BPA may be a safe treatment option for the patients with CTEPD without PH that can alleviate symptoms, improve exercise capacity, and facilitate weaning from home oxygen therapy. Further prospective randomized trials are needed to confirm these findings.

Creating a digital approach for promoting physical activity in pediatric pulmonary hypertension: A framework for future interventions.

Children with pulmonary hypertension (PH) often demonstrate limited exercise capacity. Data support exercise as an effective nonpharmacologic intervention among adults with PH. However, data on exercise training in children and adolescents are limited, and characteristics of the optimal exercise program in pediatric PH have not been identified. Exercise programs may have multiple targets, including muscle deficits which are associated with exercise limitations in both adult and pediatric PH. Wearable accelerometer sensors measure physical activity volume and intensity in the naturalistic setting and can facilitate near continuous data transfer and bidirectional communication between patients and the study team when paired with informatics tools during exercise interventions. To address the knowledge gaps in exercise training in pediatric PH, we designed a prospective, single arm, nonrandomized pilot study to determine feasibility and preliminary estimates of efficacy of a 16-week home exercise intervention, targeting lower extremity muscle mass and enriched by wearable mobile health technology. The exercIse Training in pulmONary hypertEnsion (iTONE) trial includes (1) semistructured exercise prescriptions tailored to the participant's baseline level of activity and access to resources; (2) interval goal setting fostering self-efficacy; (3) real time monitoring of activity via wearable devices; (4) a digital platform enabling communication and feedback between participant and study team; (5) multiple avenues to assess participant safety. This pilot intervention will provide information on the digital infrastructure needed to conduct home-based exercise interventions in PH and will generate important preliminary data on the effect of exercise interventions in youth with chronic cardiorespiratory conditions to power larger studies in the future.

Improvement in idiopathic interstitial pneumonia by adding macitentan to a patient unresponsive to nintedanib.

A 69-year-old woman was diagnosed with idiopathic interstitial pneumonia (IIP). The patient underwent a combination therapy of steroid therapy and intravenous cyclophosphamide, long-term oxygen therapy, and the initiation of Nintedanib. However, there was no improvement in IIP, and as a result, the activities of daily living also declined. As one of the various examinations conducted, the results of the right heart catheterization diagnosed the patient with mild pulmonary hypertension, and Macitentan therapy was initiated. The subsequent clinical course appeared to show an improvement in Idiopathic Interstitial Pneumonia (IIP) by adding Macitentan therapy to Nintedanib therapy.

Coronary Cameral Fistula: A Rare Case Presenting With Non-ST-Segment Elevation Myocardial Infarction and Pulmonary Arterial Hypertension.

Coronary cameral fistulas (CCFs) are uncommon congenital or acquired anomalies characterized by abnormal connections between a coronary artery and a cardiac chamber. While often asymptomatic and incidentally detected, symptomatic presentations are rare, and symptoms may vary depending on the size and location of the fistula. We present the case of a 67-year-old female with complaints of intermittent typical cardiac chest pain and exertional dyspnea. Further evaluation revealed a CCF originating from the left anterior descending coronary artery and the left ventricle. Additionally, the patient was found to have pulmonary hypertension on right heart catheterization. This case highlights the importance of considering CCF in the differential diagnosis of chest pain, particularly in the presence of atypical symptoms and associated pulmonary hypertension (WHO Group 4). Further research is warranted to elucidate the optimal management strategies for symptomatic CCF, especially in cases complicated by pulmonary hypertension.

Autophagy and ubiquitin-dependent proteolysis processes in left ventricular mass loss in pulmonary arterial hypertension.

The goal of this study was to evaluate the intensity of autophagy and ubiquitin-dependent proteolysis processes occurring in myocardium of left ventricle (LV) in subsequent stages of pulmonary arterial hypertension (PAH) to determine mechanisms responsible for LV mass loss in a monocrotaline-induced PAH rat model. LV myocardium samples collected from 32 Wistar rats were analyzed in an early PAH group (n = 8), controls time-paired (n = 8), an end-stage PAH group (n = 8), and their controls (n = 8). Samples were subjected to histological analyses with immunofluorescence staining, autophagy assessment by western blotting, and evaluation of ubiquitin-dependent proteolysis in the LV by immunoprecipitation of ubiquitinated proteins. Echocardiographic, hemodynamic, and heart morphometric parameters were assessed regularly throughout the experiment. Considerable morphological and hemodynamic remodeling of the LV was observed over the course of PAH. The end-stage PAH was associated with significantly impaired LV systolic function and a decrease in LV mass. The LC3B-II expression in the LV was significantly higher in the end-stage PAH group compared to the early PAH group (p = 0.040). The measured LC3B-II/LC3B-I ratios in the end-stage PAH group were significantly elevated compared to the controls (p = 0.039). Immunofluorescence staining showed a significant increase in the abundance of LC3 puncta in the end-stage PAH group compared to the matched controls. There were no statistically significant differences in the levels of expression of all ubiquitinated proteins when comparing both PAH groups and matched controls. Autophagy may be considered as the mechanism behind the LV mass loss at the end stage of PAH.

Zinc attenuates monocrotaline-induced pulmonary hypertension in rats through upregulation of A20.

Pulmonary hypertension (PH) is characterized by excessive proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs), in which inflammatory signaling caused by activation of the NF-κB pathway plays an important role. A20 is an important negative regulator of the NF-κB pathway, and zinc promotes the expression of A20 and exerts a protective effect against various diseases (e.g. COVID19) by inhibiting the inflammatory signaling. The role of A20 and intracellular zinc signaling in PH has been explored, but the extracellular zinc signaling is not well understood, and whether zinc has protective effects on PH is still elusive. Using inductively coupled plasma mass spectrometry (ICP-MS), we studied the alteration of trace elements during the progression of monocrotaline (MCT)-induced PH and found that serum zinc concentration was decreased with the onset of PH accompanied by abnormalities of other three elements, including copper, chromium, and magnesium. Zinc chloride injection with the dosage of 5 mg/kg intraperitoneally partially corrected this abnormality and inhibited the progression of PH. Zinc supplementation induced the expression of A20 in lung tissue and reduce the inflammatory responses. In vitro, zinc supplementation time-dependently upregulated the expression of A20 in PASMCs, therefore correcting the excessive proliferation and migration of cells caused by hypoxia. Using genetically encoded-FRET based zinc probe, we found that these effects of zinc ions are not achieved by entering cells, but most likely by activating cell surface zinc receptor (ZnR/GPR39). These results provide the first evidence of the effectiveness of zinc supplementation in the treatment of PH.

Interleukin(IL)-1/IL-6-inhibitor-associated drug reaction with eosinophilia and systemic symptoms (DReSS) in systemic inflammatory illnesses.

BACKGROUND: After introducing interleukin(IL)-1/IL-6 inhibitors, some Still and Still-like patients developed unusual often fatal pulmonary disease. This complication was associated with scoring as DReSS (drug reaction with eosinophilia and systemic symptoms) implicating these inhibitors, although DReSS can be difficult to recognize in the setting of systemic inflammatory disease. OBJECTIVE: We sought to facilitate recognition of IL-1/IL-6 inhibitor-DReSS in systemic inflammatory illnesses (Still/Still-like) by looking at timing and reaction-associated features. We evaluated outcomes of stopping or not-stopping IL-1/IL-6-inhibitors after DReSS reaction began. METHODS: In an international study collaborating primarily with pediatric specialists, we characterized features of 89 drug-reaction cases versus 773 drug-exposed controls and compared outcomes of 52 cases stopping IL-1/IL-6-inhibitors to 37 cases not-stopping these drugs. RESULTS: Before reaction began, drug-reaction cases and controls were clinically comparable, except for younger disease onset age for reaction cases with pre-existing cardiothoracic comorbidities. After reaction began, increased rates of pulmonary complications and macrophage activation syndrome (MAS), differentiated drug-reaction cases from drug-tolerant controls (p=4.7x10-35; p=1.1x10-24, respectively). Initial DReSS feature was typically reported 2-8 weeks after initiating IL-1/IL-6-inhibition. In drug-reaction cases stopping versus not-stopping IL-1/IL-6-inhibitor treatment, reaction related features were indistinguishable, including pulmonary complication rates [75%(39/52] versus [76%(28/37)]. Those stopping subsequently required fewer medications for treatment of systemic inflammation, had decreased rates of MAS, and improved survival (p=0.005, multivariate regression). Resolution of pulmonary complications occurred in 67%(26/39) of drug-reaction cases who stopped and in none who continued inhibitors. CONCLUSIONS: In systemic inflammatory illnesses, recognition of IL-1/IL-6-inhibitor-associated reactions followed by avoidance of IL-1/IL-6-inhibitors significantly improved outcomes.

Under pressure: symptomatic pulmonary hypertension is a predictor of poor outcome following hip fracture.

INTRODUCTION: Pulmonary hypertension (PHTN) is associated with increased morbidity and mortality in noncardiac surgery and elective surgery. This population of patients has a low physiological reserve and is prone to cardiac arrest as a result. This study aims to identify the impact that PHTN has on outcomes among geriatric hip fracture patients. METHODS: A 3:1 propensity-score-matched retrospective case (PHTN)-control (no PHTN [N]) study of hip fracture patients from 2014 to 2022 was performed. Patients were matched utilizing propensity score matching of a validated geriatric trauma risk assessment tool (STTGMA). All patients were reviewed for hospital quality measures and outcomes. Comparative univariable and multivariable analyses were conducted between the two matched cohorts. A sub-analysis compared patients across PHTN severity levels (mild, moderate, severe) based on pulmonary artery systolic pressures (PASP) as measured by transthoracic echocardiogram. RESULTS: PHTN patients (n = 67) experienced a higher rate of inpatient, 30-day, and 1-year mortality, major complications, and 90-day readmissions as compared to the N cohort (n = 201). PHTN patients with a PASP > 60 experienced a significantly higher rate of major complications, need for ICU, longer admission length, and worse 1-year functional outcomes. Pulmonary hypertension was found to be independently associated with a 3.5 × higher rate of 30-day mortality (p = 0.016), 2.7 × higher rate of 1-year mortality (p = 0.008), 2.5 × higher rate of a major inpatient complication (p = 0.028), and 1.2 × higher rate of 90-day readmission (p = 0.044). CONCLUSION: Patients who had a prior diagnosis of pulmonary hypertension before sustaining their hip fracture experienced significantly worse inpatient and post-discharge outcomes. Those with a PASP > 60 mmHg had worse outcomes within the PHTN cohort. Providers must recognize these at-risk patients at the time of arrival to adjust care planning accordingly. LEVEL OF EVIDENCE: III.

xTrends in racial and ethnic disparities in pediatric lung transplantation in the United States.

BACKGROUND: Racial and ethnic disparities in pediatric lung transplantation (LTx) related to the shifting cystic fibrosis (CF) population receiving highly effective modulator therapy (HEMT) has not been well investigated. METHODS: The UNOS Registry was queried for patients age 1-25 years undergoing bilateral LTx between 1 January 2012 and 31 December 2021. Race and ethnicity were classified as non-Hispanic White, non-Hispanic Black, Hispanic, or none of the above. The primary outcome was posttransplant mortality. Trends in the association between race/ethnicity and mortality were examined using transplant year as a continuous variable and stratifying year based on introduction of HEMT (triple combination therapy) in November 2019. RESULTS: In the study sample (N = 941), 7% of patients were non-Hispanic Black, 15% were Hispanic, and 2% were some other racial or ethnic group. One hundred (11%) received LTx after approval of triple combination therapy, and 407 (43%) died during follow-up. We identified a statistically significant disparity in mortality hazard (hazard ratio: 1.91; 95% confidence interval: 1.31, 2.80) in non-Hispanic Black compared to non-Hispanic White patients in the pre-triple combination therapy era. CONCLUSIONS: We found higher mortality hazard among non-Hispanic Black compared to non-Hispanic White children undergoing LTx in the United States. Further monitoring of LTx outcomes to identify and address disparities is needed in the current era of triple combination therapy for CF.

Association between Thoracic Radiographic Changes and Indicators of Pulmonary Hypertension in Dogs with Heartworm Disease.

Pulmonary hypertension (PH) is a consequence of pulmonary endarteritis during infection with Dirofilaria immitis in dogs. Echocardiography is the technique of choice but is not always accessible to all clinicians. This study aimed to evaluate the association of the radiological findings in dogs with heartworm disease and the presence or absence of echocardiographically characterised PH. The study included 62 heartworm-infected dogs that underwent thoracic radiographs and echocardiography. The studied dogs showed moderate to severe PH when the Right Pulmonary Artery Distensibility (RPAD) Index was <29.5%. The RPAD Index was used for comparison with thoracic radiographs. The Vertebral Heart Size (VHS), right cranial pulmonary artery passing through the fourth rib in the laterolateral projection (CrPA/R4) ratio, and right caudal pulmonary artery to the ninth rib in the dorsoventral projection (CdPA/R9) ratio showed significant differences between dogs with/without PH (p < 0.001). Sensitivity (sen) and specificity (sp) cut-off values were obtained: VHS ≥ 9.53 (sen 93.75%, sp 63.33%); CrPA/R4 ≥ 1.08 (sen 87.5%, sp 70%); and CdPA/R9 ≥ 1.10 (sen 96.88%, sp 76.66%). The CrPA/R4 and CdPA/R9 ratios showed potential as a preliminary screening tool for PH in heartworm-infected dogs, suggesting that they may reliably indicate the presence of PH and guide the decision for further diagnostic testing.