ABSTRACT Idiopathic pulmonary arterial hypertension (IPAH) is a pulmonary vascular disease with a poor prognosis. Its pathogenesis remains unclear and the treatment methods are limited. The expression of tRNA‐derived small RNA (tsRNA) in IPAH tissues remains unknown. tsRNA sequencing was conducted on lung tissue samples obtained from patients with IPAH and healthy controls. Differentially expressed tsRNAs were identified and their expression levels were validated using qRT‐PCR. Functional enrichment analysis was performed to explore the potential biological roles of these tsRNAs. Lung tissue samples from three patients with IPAH and three control subjects were sequenced. A total of 382 differential tRFs and tsRNAs were identified (200 upregulated and 182 downregulated). Ten tsRNAs with the most significant differential expression were selected for further investigation. qRT‐PCR analysis revealed that all five upregulated tsRNAs exhibited expression trends consistent with the sequencing results, whereas only two of the five downregulated tsRNAs showed consistency. Bioinformatics analysis predicted that five upregulated tsRNAs target the same gene, TENT4A; among them, tiRNA‐1:35‐Leu‐TAG‐2 was experimentally confirmed by dual‐luciferase reporter assay. Analysis of GSE15197 and GSE113439 indicated that TENT4A expression was significantly lower in IPAH samples compared with that in the controls. Further research indicates that tiRNA‐1:35‐Leu‐TAG‐2 directly targets TENT4A and functions dependent on TENT4A. tsRNA dysregulation may play a potential role in the development of IPAH. TENT4A is a potential critical target in the pathogenesis and treatment of IPAH.
ABSTRACT Right heart catheterization defines pulmonary hypertension (PH) hemodynamics, but simple markers of pulmonary vascular load remain useful. Inferior‐lead T‐wave inversion (TWI) is seen in right ventricular pressure overload; its association with pulmonary vascular resistance (PVR) and prognosis is uncertain. We retrospectively studied a cohort of 98 patients who underwent electrocardiography (ECG), echocardiography, and right heart catheterization within 48 h from 2021 to 2023. Inferior TWI amplitudes in leads II, III, and aVF were measured as absolute values and summed. Associations with PVR, performance for PVR > 5 Wood units, and all‐cause mortality were evaluated. Twenty‐five patients (26%) had PVR > 5 Wood units. The inferior TWI sum correlated with PVR ( ρ = 0.326, p = 0.001) and discriminated PVR > 5 Wood units better than conventional ECG markers (area under the curve, 0.78). A cutoff > 0.10 mV yielded 72% sensitivity, 84% specificity, and an odds ratio of 13.1 (95% confidence interval [CI], 4.5–38.1; p < 0.001). During a median follow‐up of 731 days, 19 patients died. Inferior TWI sum > 0.15 mV was associated with higher mortality (log‐rank p = 0.015) and remained associated after adjustment for age and log 2 N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) (hazard ratio, 3.83; 95% CI, 1.48–9.90; p = 0.007). Adding this ECG marker increased the global chi‐square from 12.0 to 19.3. Quantitative inferior‐lead TWI was associated with high PVR and all‐cause mortality in patients evaluated for PH. It may complement non‐invasive assessment and right heart catheterization but requires external validation.
ABSTRACT We report the case of an 18‐year‐old female with progressive, end‐stage pulmonary arterial hypertension (PAH) despite receiving maximal triple combination therapy. The patient had a history of patent ductus arteriosus (PDA) closure at 15 months of age. Due to a pulmonary hypertensive crisis during anesthesia induction, a transcatheter Potts procedure was successfully performed under extracorporeal membrane oxygenation (ECMO) support, involving covered stent implantation just below the previous PDA occluder. At the 3‐month follow‐up, the patient demonstrated significant clinical improvement, shifting to WHO class II–III, with a dramatic decrease in NT‐proBNP (5406–512 pg/ml) and an increased 6‐min walk distance (< 300 to 390 m). This case achieved short‐term recovery of cardiac function and long‐term maintenance of pulmonary vascular stability and demonstrates that the transcatheter Potts shunt is a feasible and effective life‐prolonging treatment option for severe PAH, even in patients with a history of prior PDA closure.
ABSTRACT Pulmonary hypertension (PH) is a progressive disease associated with high morbidity and mortality. Despite advancements, gaps in PH care quality persist, though the drivers of these gaps are incompletely understood. Thus, we sought to explore patient and provider perspectives on high‐quality PH care. We conducted a multi‐site qualitative study at three expert PH centers in the United States, involving telephone interviews with 20 providers and 22 patients. We conducted a reflexive thematic analysis, using the Institute of Medicine's (IOM) six domains of healthcare quality (safe, effective, patient‐centered, timely, efficient, and equitable) as an a priori coding scheme, with subcodes developed under each domain. We then compared codes across IOM domains and patient and provider data to identify overarching themes. Our analysis revealed three cross‐cutting themes that encompassed all six IOM healthcare quality domains, covered all identified subcodes, and represented both provider and patient perspectives: (1) “It takes a village,” that is, the expansive team needed to provide care for a patient with PH; (2) The need for care coordination within a PH center, with specialty pharmacies, and with community providers; and (3) PH centers as a model to deliver high‐quality care. Finally, participants offered clear recommendations for addressing gaps in care quality, including expanding village members, such as the addition of social workers, improving care coordination by improving patient follow‐up and tracking, and expanding access to PH centers by having a PH center presence in the community. These findings highlight key areas for targeted improvements in PH care quality.
ABSTRACT Assessment of right atrial (RA) structure helps monitor right heart (RH) function, critical for prognosis in pulmonary arterial hypertension (PAH). This study aims to assess the prognostic value of RA adverse remodeling (RAAR) with targeted therapy in PAH. Patients diagnosed with PAH between June 2013 and June 2024 were prospectively recruited. Right atrial reverse remodeling (RAAR) was defined by the relative change in right atrial diameter (RAD) on 1‐year follow‐up echocardiography (ECHO). RAAR was defined as a RAD decrease of < 13% or any increase from baseline, as determined by receiver operating characteristic curve analysis. The primary composite endpoint included heart failure‐related readmission, all‐cause mortality, and lung transplantation. Of 240 patients enrolled, 234 completed 1‐year follow‐up, with a median follow‐up duration of 37.5 months (interquartile range: 23.3–57.5 months). RAAR was observed in 168 patients (71.8%), and baseline RAD was its sole independent predictor (OR 0.941, p = 0.012). RAAR was associated with significantly poorer event‐free survival in both the low‐risk group (log‐rank p = 0.037) and the intermediate‐/high‐risk group (log‐rank p < 0.001). Adding RAAR improved the ESC model (χ 2 : 18.08–21.83) and the three‐strata COMPERA model (χ 2 : 22.65–28.04). These findings suggest that RAAR is a key indicator for evaluating prognosis in PAH patients, holding promise for reflecting treatment response and predicting clinical outcomes in PAH.
