Predictors of exercise-induced pulmonary hypertension in patients with connective tissue disease.

Screening and early detection of pulmonary arterial hypertension (PAH) in connective tissue disease (CTD) are currently recommended for early treatment. Exercise-induced pulmonary hypertension (EIPH) is thought to be a potential risk of developing resting pulmonary hypertension. However, accurate diagnosis of EIPH is needed hemodynamics by right heart catheterization during exercise. Therefore, we compared various parameters of EIPH group with non-EIPH group in patients with CTD. This study aimed to investigate noninvasive predictors of EIPH. A total of 162 consecutive patients with CTD who received screening of PAH was studied. Thirty-four patients with suspected PAH received right heart catheterization (RHC) at rest. Twenty-four patients without PAH underwent RHC during exercise, and they were divided into the EIPH group (n = 7) and the non-EIPH group (n = 17). Exercise tolerance such as 6-min walk distance and peak VO2/kg in the EIPH group was lower than that in the non-EIPH group. For hemodynamics, pulmonary artery pressure, right atrial pressure, and vascular resistance in the EIPH group were significantly higher than those in the non-EIPH group. In echocardiography, RV Tei index in the EIPH group was significantly higher than that in the non-EIPH group (EIPH vs non-EIPH = 0.42 [0.41, 0.47] vs 0.25 [0.20, 0.32], P = 0.007). The receiver operating characteristics curve showed a cutoff value of RV Tei index (0.41) with a sensitivity of 0.857 and specificity of 0.882. In conclusion, RV Tei index might be a feasible predictor of EIPH in patients with CTD.

Association of delayed diagnosis of pulmonary arterial hypertension with its prognosis.

BACKGROUND: Currently, pulmonary hypertension-targeted therapy has been shown to improve the survival of patients with pulmonary artery hypertension (PAH). However, the importance of early diagnosis has not been investigated. Therefore, this study aimed to investigate whether a delayed diagnosis of PAH is associated with its prognosis. METHODS AND RESULTS: A total of 66 consecutive untreated patients were diagnosed with PAH from January 2008 to December 2021 at the Kagoshima University Hospital. The time from symptom onset to diagnosis correlated with brain natriuretic peptide levels (p < 0.001), right ventricle (RV) Tei index (p < 0.001), and the tricuspid annular plane systolic excursion/systolic pulmonary artery pressure ratio (p = 0.003). These findings suggest that in patients with PAH, RV function declines with increasing time from symptom onset to diagnosis. Furthermore, older patients with PAH appeared to have a longer time from symptom onset to diagnosis. Next, patients were divided into delayed diagnosis (>3 months) and early diagnosis (≤3 months) groups based on the time from symptom onset to diagnosis. Patients were categorized into three groups according to the European Society of Cardiology (or the European Respiratory Society) risk stratification guidelines. Patients diagnosed with PAH within 3 months of symptom onset were significantly in the low- or intermediate-risk groups (p < 0.001). A Kaplan-Meier analysis revealed that the cumulative event-free rate was significantly lower (p < 0.01) in the delayed diagnosis group than in the early diagnosis group. A delayed diagnosis was significantly associated with a worse outcome than an early diagnosis, after adjusting for different sets of confounding factors. CONCLUSIONS: A delayed PAH diagnosis is associated with a poor prognosis. Early diagnosis of PAH may lead to a low-risk treatment. Furthermore, older patients need more careful screening for PAH.

Pulmonary artery hypertension-associated with human immunodeficiency virus infection with attenuated effect of subcutaneous treprostinil injection during long-term observation: A case report.

Pulmonary artery hypertension associated with human immunodeficiency virus infection (PAH-HIV) is known to be caused by HIV infection. Antiretroviral therapy and PAH-specific drugs improve the prognosis of patients with PAH-HIV, but the pathophysiology of PAH-HIV remains unclear. We report a case of PAH-HIV treated with upfront combination therapy including subcutaneous injection of treprostinil. One year after treatment initiation, the patient's PAH improved significantly. However, it worsened over time due to reduced efficacy of subcutaneous injection of treprostinil. Learning objective: The etiology and pathophysiology of pulmonary artery hypertension associated with human immunodeficiency virus infection (PAH-HIV) remain unclear, and there are few case reports of PAH-HIV in Japan because the HIV prevalence is low. We encountered a case of PAH-HIV in which the efficacy of subcutaneous treprostinil injection was attenuated. It was unclear whether the reduced efficacy was associated with the pathophysiology of PAH-HIV. When PAH control deteriorates, early alteration of medication choice and administration route is important.

Unknown atrial septal defect was diagnosed during the course of treatment for portopulmonary hypertension: A case report.

Portopulmonary hypertension (POPH) is a condition defined by the development of pulmonary arterial hypertension (PAH) that is associated with liver disease or portal hypertension. Untreated POPH has a poor prognosis. POPH can be treated with PAH-targeted therapy and can sometimes resolve with liver transplantation (LT); however, poorly controlled POPH can preclude LT owing to an increased peri-operative risk. We report a case of POPH that was diagnosed as an unknown atrial septal defect during PAH-targeted therapy. As observed in our case, the same patient may have several causes of PAH. It is important to confirm an unknown shunt disease using echocardiography during PAH-targeted therapy. Learning objective: It is difficult to detect unknown shunt disease in patients who are diagnosed with pulmonary arterial hypertension (PAH) owing to other causes. We report a case of portopulmonary hypertension that was diagnosed as an unknown atrial septal defect during PAH-targeted therapy. This report highlights the same patient may have several causes of PAH. It is important to confirm an unknown shunt disease using echocardiography during PAH-targeted therapy.

Different characteristics of mitochondrial dynamics-related miRNAs on the hemodynamics of pulmonary artery hypertension and chronic thromboembolic pulmonary hypertension.

BACKGROUND: Mitochondria are dynamic organelles that undergo fission or fusion. These mitochondrial dynamics are reported to be associated with pulmonary hypertension (PH). PH is divided into 5 groups, including pulmonary artery hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), based on its pathogenesis. However, it is still unknown whether and how miRNAs related to mitochondrial dynamics (MD) affect PAH and CTEPH. METHODS: We investigated patients who underwent right heart catheterization between October 2016 and January 2019. Out of 34 PH patients, 12 were diagnosed with PAH, and 22 were diagnosed with CTEPH. In addition, there were 30 patients diagnosed with left heart disease. We enrolled the 34 PH patients as the PH group and 30 left heart disease patients as the control group. RESULTS: Among MD-related miRNAs, the circulating levels of miR-140-3p were higher, and those of miR-485-5p were lower in the PH group than in the control group (p < 0.01), suggesting that miRNAs inducing mitochondrial fission are related to PH. The miR-140-3p levels in the PAH and CTEPH groups were higher than those in the control group (p < 0.01). The levels of miR-140-3p and miR-485-5p in the PAH group correlated with pulmonary vascular resistance (r = 0.582, p = 0.046) and cardiac index (r = -0.36, p = 0.04), respectively. The miR-485-5p levels in the CTEPH group correlated with right atrium pressure (r = -0.456, p = 0.049). CONCLUSION: MD-related miRNAs levels change to induce fission and are closely related to the hemodynamics of PAH and CTEPH.

Geriatric Nutritional Risk Index Is Associated With Prognosis in Patients With Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension.

Background: The Geriatric Nutritional Risk Index (GNRI) is a simple tool for assessing nutritional risk that predicts prognosis in patients with heart failure. This study evaluated associations between the GNRI at first hospitalization and prognosis in patients with pulmonary artery hypertension (PAH) and those with chronic thromboembolic pulmonary hypertension (CTEPH). Methods and Results: This retrospective investigation included 104 patients with either PAH or CTEPH who were treated at Kagoshima University Hospital in Japan. Patients were divided into a high (≥92) and low (<92) GNRI groups. Body mass index and serum albumin levels were significantly lower in the low GNRI group (P<0.001). Over a median follow-up period of 24 months, the incidence of pulmonary hypertension rehospitalization was higher in the low GNRI group (P=0.04). Kaplan-Meier analysis revealed that the cumulative event-free rate was significantly lower in the low GNRI group (P=0.002). Low GNRI was significantly associated with a poorer outcome after adjusting for different sets of confounding factors, including: age and sex (P=0.004); age, sex, and PAH (P=0.043); and age, sex, and mean pulmonary artery pressure (P=0.003). Conclusions: The GNRI at first hospitalization is useful for predicting prognosis in PAH and CTEPH patients.

The potential for early diagnosis of pulmonary arterial hypertension using lung iodine-123-metaiodobenzylguanidine (123I-MIBG) uptake: A case report.

Previous reports have found evidence that the lung uptake of iodine-123-metaiodobenzylguanidine (123I-MIBG) represents pulmonary vascular endothelial function. Therefore, it was believed that the reduced lung uptake of 123I-MIBG in patients with pulmonary artery hypertension may indicate poor pulmonary vascular endothelial function in those patients. In our previous report, we analyzed the lung uptake of 123I-MIBG in patients with pulmonary hypertension, and demonstrated that it is lower in patients with pulmonary arterial hypertension (PAH) than in those with chronic thromboembolic pulmonary hypertension and controls, suggesting that reduced uptake of 123I-MIBG in patients with PAH indicates endothelial dysfunction of the pulmonary artery. In the current report, we describe a 46-year-old woman diagnosed with scleroderma whose lung uptake of 123I-MIBG was decreased on admission, but she was not diagnosed with pulmonary artery hypertension at that time because her pulmonary artery pressure during right heart catheterization was not elevated. However, she was diagnosed with borderline PAH 2 years later. The lung uptake of 123I-MIBG was reduced before a reduction in %DLCO was observed. This report suggests that the lung uptake of 123I-MIBG may be useful for the early diagnosis of pulmonary artery hypertension.