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.

Association of infective endocarditis caused by Abiotrophia defectiva with mycotic aneurysm formation: A case report and the review of the literature.

A 74-year-old woman with a history of mitral valve prolapse with mitral regurgitation was transferred to our hospital due to infective endocarditis. Blood culture revealed Abiotrophia defectiva which is known as a nutritional variant streptococcus. Transesophageal echocardiography revealed posterior leaflet (P2) prolapse due to rupture of tendon chordae with severe mitral regurgitation and vegetation on posterior leaflet. Magnetic resonance imaging (MRI) revealed multiple infarction lesions in left temporal lobe and parietal lobe and mycotic aneurysm formation of right middle cerebral artery. Because A. defectiva cannot be cultured on non-supplemented media, their prevalence may be underreported. Learning objective: A number of causative microorganisms of infective endocarditis have been identified. Streptococci and staphylococci account for 80 % of cases of infective endocarditis. Abiotrophia defectiva does not grow in ordinary growth media and its prevalence may be underreported. It is important to know A. defectiva causes infective endocarditis with mycotic aneurysm formation.

A case of Takotsubo cardiomyopathy with apical hypertrophic cardiomyopathy-like morphological changes during recovery.

Objective: Few cases of Takotsubo cardiomyopathy with apical hypertrophic cardiomyopathy (APH)-like morphological changes during the recovery process have been reported. Patient: A 56-year-old woman diagnosed with Takotsubo cardiomyopathy showed a morphology similar to that of APH during recovery. We examined this patient using 2D speckle-tracking echocardiography based on the method used for hypertrophic cardiomyopathy, which suggested that the circumferential strain (CS) of the middle wall indicated myocardial function of the left ventricle, and the CS of the inner wall was associated with left ventricular chamber function. Results: We measured the CS of the endocardial, middle, and epicardial layers and found that the apical inner layer CS (CSinner), middle layer CS, and outer layer CS were all decreased at the onset. CSinner showed a strong tendency to recover on echocardiography performed when APH-like morphology was observed. Conclusion: The morphology of the apex in our case likely contributed to the maintenance of chamber function.

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.

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.

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.

Isolated Distal Deep Vein Thrombus Detected before Orthopedic Surgery: Is Preoperative Anticoagulation Preferable?

Objective: We evaluate the efficacy of anticoagulant administration for isolated distal deep vein thrombus (IDDVT), detected before orthopedic surgery. Materials and Methods: The study included 32 patients diagnosed with IDDVT before orthopedic surgery in our hospital between October 2011 and October 2017. They were divided into two groups: the 'pre- and post-operative therapy group,' who were administered anticoagulants both pre- and post-operatively, and the 'post-operative therapy group,' who were administered anticoagulants only after surgery due to risk of bleeding judged by an orthopedic surgeon. We compared the primary efficacy (change in IDDVT size) between the two groups. Results: The proportion of patients with increased post-operative IDDVT sizes was significantly larger in the post-operatively treated group than in the pre- and post-operatively treated group (44.4% vs. 8.7%, p=0.026). No case demonstrated an IDDVT extension proximal to the popliteal vein or presented with symptomatic pulmonary thromboembolism in this study. Conclusion: Based on our findings, we recommend that, in patients with IDDVT detected prior to orthopedic surgery and administered anticoagulant therapy only after the procedure because of a bleeding risk, a lower limb ultrasonography to re-evaluate the existing deep vein thrombus should be conducted before beginning rehabilitation.

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.

Bisoprolol Successfully Improved the Intraventricular Pressure Gradient in a Patient with Midventricular Obstructive Hypertrophic Cardiomyopathy with an Apex Aneurysm due to Apical Myocardial Damage.

Midventricular obstructive hypertrophic cardiomyopathy (MVOHCM) is a rare form of hypertrophic cardiomyopathy (HCM). An 80-year-old man was administered bisoprolol and warfarin therapies as treatment for MVOHCM with an apex aneurysm due to myocardial damage and intra-aneurysmal thrombus not complicated by atrial fibrillation. The pressure gradient in the midventricle successfully improved from 53.9 to 21.8 mmHg, and the intra-aneurysmal thrombus disappeared.

Impairment of Iodine-123-Metaiodobenzylguanidine (123I-MIBG) Uptake in Patients with Pulmonary Artery Hypertension.

According to recent studies, lung uptake of iodine-123-metaiodobenzylguanidine (123I-MIBG) is impaired in many lung diseases and low lung uptake of 123I-MIBG suggests endothelial dysfunction of the pulmonary artery. 123I-MIBG scintigraphy in patients with pulmonary hypertension (PH) has not yet been clinically evaluated. We hypothesized that the lung uptake of 123I-MIBG is reduced in patients with PH and differs among PH subtypes. The purpose of the present study was to analyze the lung uptake of 123I-MIBG in patients with PH and compare it with the data obtained by echocardiography or right heart catheterization. 123I-MIBG scintigraphy was performed in 286 consecutive patients from 2003 to 2014. We enrolled 21 patients with PH and 8 control patients. The 21 patients with PH were categorized into those with pulmonary artery hypertension (PAH, n = 12) and those with chronic thromboembolic pulmonary hypertension (CTEPH, n = 9). The mean pulmonary artery pressure was not significantly different between patients with CTEPH and PAH (37.7 ± 6.8 versus 32.3 ± 5.3 mmHg respectively; P = 0.054). There were no significant differences in any other hemodynamic parameters between the two groups. The lung uptake of 123I-MIBG in PAH patients (early image: 1.54 ± 0.18, delayed image: 1.41 ± 0.16) was significantly lower than that of CTEPH patients (early image: 2.17 ± 0.25, P < 0.0001; delayed image: 1.99 ± 0.20, P = 0.0001, adjusted for age and World Health Organization classification) and controls (early image: 2.32 ± 0.27, P = 0.0007; delayed image: 1.92 ± 0.19, P = 0.0007). In conclusion, we found for the first time that the lung uptake of 123I-MIBG in patients with PAH is lower than that in patients with CTEPH and controls.

Successful antemortem diagnosis and treatment of pulmonary tumor thrombotic microangiopathy.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal cancer-related complication with rapid progression. Although the underlying molecular mechanisms of PTTM remain unclear, platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) may play important roles in the pathogenesis of PTTM. We herein report a case of PTTM that was diagnosed antemortem by pathology using pulmonary wedge aspiration. The patient was treated with a combination therapy of imatinib (PDGF receptor antagonist), bevacizumab (VEGF receptor inhibitor), S-1, and cisplatin. These findings suggest that molecular-target drugs are effective for the treatment of PTTM.