Prognostic analysis of pulmonary hypertension with lung parenchymal lesion: Comparison of mortality with and without connective tissue disease.

BACKGROUND: The prognosis of pulmonary hypertension (PH) associated with connective tissue diseases related to interstitial pneumonia (CTD-IP PH) is relatively good among patients with PH and lung disease. However, the impact of pulmonary vasodilator treatment on the prognosis of CTD-IP PH compared with that of PH-induced chronic lung disease (group-3 PH) remains unclear. METHODS: From 2012 to 2022, 50 patients with lung parenchymal lesions diagnosed with PH (mean pulmonary arterial pressure >20 mmHg) at Juntendo University Hospital were divided into two groups: CTD-IP PH (30 patients) and group 3-PH (20 patients). The impact of pulmonary vasodilator treatment and the use of long-term oxygen therapy (LTOT) on the prognosis of each group was examined retrospectively. RESULTS: The prognosis of CTD-IP PH was significantly better compared to group-3 PH. While the treatment with pulmonary vasodilators did not affect the prognosis in group 3-PH, the prognosis of the patients treated with vasodilators in the CTD-IP PH group was significantly better than that of the non-treated patients. Treatment with multi-pulmonary vasodilators did not affect the prognosis in CTD-IP PH. Although the prognosis for the patients with LTOT was poor in all registered patients in the present study, treatment with pulmonary vasodilators improved the prognosis even under the use of LTOT in CTD-IP PH (P = 0.002). In a multivariate analysis of the CTD-IP PH group, pulmonary vasodilator treatment was an independent factor for better prognosis. CONCLUSION: Treatment with a pulmonary vasodilator for CTD-IP PH may improve the prognosis, even in patients requiring LTOT.

Tofogliflozin, a sodium-glucose cotransporter 2 inhibitor, improves pulmonary vascular remodeling due to left heart disease in mice.

BACKGROUND: Group 2 pulmonary hypertension (PH) represents PH caused by left heart disease (PH-LHD). LHD induces left-sided filling and PH, finally leading to pulmonary vascular remodeling. Tofogliflozin (TOFO) is a sodium-glucose cotransporter 2 (SGLT2) inhibitor used in the treatment of diabetes. Recent studies have shown that SGLT2 inhibitors have beneficial effects on heart failure, but the effects of SGLT2 inhibitors on PH-LHD remain unclear. We hypothesized that TOFO has protective effects against pulmonary vascular remodeling in PH-LHD mice. METHODS: We generated two murine models of PH-LHD: a transverse aortic constriction (TAC) model; and a high-fat diet (HFD) model. C57BL/6J mice were subjected to TAC and treated with TOFO (3 mg/kg/day) for 3 weeks. AKR/J mice were fed HFD and treated with TOFO (3 mg/kg/day) for 20 weeks. We then measured physical data and right ventricular systolic pressure (RVSP) and performed cardiography. Human pulmonary artery smooth muscle cells (PASMCs) were cultured and treated with TOFO. RESULTS: Mice treated with TOFO demonstrated increased urine glucose levels. TAC induced left ventricular hypertrophy and increased RVSP. TOFO treatment improved RVSP. HFD increased body weight (BW) and RVSP compared with the normal chow group. TOFO treatment ameliorated increases in BW and RVSP induced by HFD. Moreover, PASMCs treated with TOFO showed suppressed migration. CONCLUSIONS: TOFO treatment ameliorated right heart overload and pulmonary vascular remodeling for PH-LHD models, suggesting that SGLT2 inhibitors are effective for treating PH-LHD.

Circulating sLR11 levels predict severity of pulmonary hypertension due to left heart disease.

BACKGROUND: Heart failure is a severe condition often involving pulmonary hypertension (PH). Soluble low-density lipoprotein receptor with 11 ligand-binding repeats (sLR11) has been associated with pulmonary artery hypertension. We examined whether sLR11 correlates with PH in left heart disease and can be used as a predictive marker. METHOD: We retrospectively analyzed patients with severe mitral regurgitation who underwent right heart catheterization before surgery for valve replacement or valvuloplasty from November 2005 to October 2012 at Juntendo University. We measured sLR11 levels before right heart catheterization and analyzed correlations with pulmonary hemodynamics. We compared prognoses between a group with normal sLR11 (≤9.4 ng/ml) and a group with high sLR11 (>9.4 ng/ml). Follow-up was continued for 5 years, with end points of hospitalization due to HF and death due to cardiovascular disease. RESULTS: Among 34 patients who met the inclusion criteria, sLR11 correlated with mean pulmonary artery pressure (r = 0.54, p<0.001), transpulmonary pressure gradient (r = 0.42, p = 0.012), pulmonary vascular resistance (r = 0.36, p<0.05), and log brain natriuretic peptide (BNP). However, logBNP did not correlate with pulmonary vascular resistance (p = 0.6). Levels of sLR11 were significantly higher in the 10 patients with PH (14.4±4.3 ng/ml) than in patients without PH (9.9±3.9 ng/ml; p = 0.002). At 5 years, the event rate was higher in the high-sLR11 group than in the normal-sLR11 group. The high-sLR11 group showed 5 hospitalizations due to HF (25.0%) and 2 deaths (10.0%), whereas the normal-sLR11 group showed no hospitalizations or deaths. Analyses using receiver operating characteristic curves showed a higher area under the concentration-time curve (AUC) for sLR11 level (AUC = 0.85; 95% confidence interval (CI) = 0.72-0.98) than for BNP (AUC = 0.80, 95%CI = 0.62-0.99) in the diagnosis of PH in left heart disease. CONCLUSIONS: Concentration of sLR11 is associated with severity of PH and offers a strong predictor of severe mitral regurgitation in patients after surgery.

Elevated Heart Rate in Combination with Elevated Blood Pressure Predicts Lower Cardiovascular Mortality in Acute Decompensated Heart Failure.

Despite its clinical relevance, a subclass of acute decompensated heart failure (ADHF) with elevated blood pressure, known as hypertensive ADHF (HT-ADHF), has been less intensively evaluated. This study aimed to characterize the prognostic nature and pathophysiology of HT-ADHF. A total of 509 consecutive patients with first-time ADHF hospitalization were subjects of the study. Participants were divided into two groups: an HT-ADHF group (systolic blood pressure, SBP > 140 mmHg at presentation) and a non-HT-ADHF group (SBP ≤ 140 mmHg). Median follow-up duration measured 253 days. Unadjusted Kaplan-Meier analysis demonstrated both a lower cardiovascular mortality rate in the HT-ADHF group and similar incidences of heart failure rehospitalization in both groups. Adjusted Cox hazard analysis showed an association of elevated SBP at presentation with significantly lower cardiovascular mortality, though no such association was observed with heart failure rehospitalization. Moreover, elevated heart rate in combination with elevated SBP at presentation predicted a significantly lower risk of cardiovascular mortality (Hazard Ratio: 0.32, 95% CI: 0.14-0.77, P = 0.01). Also, significantly lower cardiovascular mortality was observed in this subtype, compared with other types of ADHF.

Reduced Number of Platelets During Intra-Aortic Balloon Pumping Counterpulsation Predicts Higher Cardiovascular Mortality After Device Removal in Association with Systemic Inflammation.

Thrombocytopenia is a frequent complication in patients requiring intra-aortic balloon pumping (IABP) counterpulsation. However, its prognostic impact has not been fully addressed. The objective of this study is to evaluate the impact of the change in the platelet number during IABP use on the prognosis after device removal.This is a retrospective observational study. Patients in the intensive cardiac care unit at three Juntendo University hospitals who underwent percutaneous implantation of IABP with or without veno-arterial extracorporeal membrane oxygenation (V-A ECMO), since 2012-2016, were enrolled in the study (n = 439). Patients who died during mechanical circulatory support (n = 47) were excluded. We evaluated the prognostic impact of the ratio of platelet reduction from the baseline (% PLT reduction) during IABP use on cardiovascular mortality after device removal.The median and the range of follow-up period were 298 days and 0-1,869 days, respectively. Unadjusted Kaplan-Meier analysis demonstrated that patients with a higher % PLT reduction had higher cardiovascular (CV) mortality. An adjusted Cox proportional hazard analysis demonstrated that a 10% higher % PLT reduction was associated with higher cardiovascular (CV) mortality (Hazard ratio: 1.3, 95% Confidence interval: 1.1-1.6, P < 0.001). Moreover, % PLT reduction and the maximum C-reactive protein (CRP) level during IABP use were positively correlated (r = 0.326, P < 0.001).The reduced number of platelets during IABP use was associated with an increased risk of CV mortality.

Correlation of Nutritional Indices on Admission to the Coronary Intensive Care Unit with the Development of Delirium.

BACKGROUND: Delirium is a common occurrence in patients admitted to the intensive care unit and is related to mortality and morbidity. Malnutrition is a predisposing factor for the development of delirium. Nevertheless, whether the nutritional status on admission anticipates the development of delirium in patients with acute cardiovascular diseases remains unknown. OBJECTIVE: This study aims to assess the correlation between the nutritional status on admission using the nutritional index and the development of delirium in the coronary intensive care unit. DESIGN: We examined 653 consecutive patients (mean age: 70 ± 14 years) admitted to the coronary intensive care unit of Juntendo University Hospital between January 2015 and December 2016. We evaluated three nutritional indices frequently used to assess the nutritional status, i.e., Geriatric Nutritional Risk Index (GNRI), Prognostic Nutritional Index (PNI), and Controlling Nutritional Status (CONUT). We defined delirium as patients with a delirium score >4 using the Intensive Care Delirium Screening Checklist. RESULTS: Delirium was present in 58 patients. All nutritional indices exhibited a tendency for malnutrition in the delirium group compared with the non-delirium group (GNRI, 86.5 ± 9.38 versus 91.6 ± 9.89; PNI, 36.4 ± 6.95 versus 41.6 ± 7.62; CONUT, 5.88 ± 3.00 versus 3.61 ± 2.56; for all, p < 0.001). Furthermore, the maximum delirium score increased progressively from the low- to the high-risk group, as evaluated by each nutritional index (GNRI, PNI, CONUT; for all, p < 0.001). A multivariate analysis revealed that the PNI and CONUT were independent risk factors for the occurrence of delirium. CONCLUSIONS: A marked correlation exists between the nutritional index on admission, especially PNI and CONUT, and the development of delirium in patients with acute cardiovascular diseases, suggesting that malnutrition assessment upon admission could help identify patients at high risk of developing delirium.

[Chronic myeloid leukemia complicated by pulmonary hypertension during dasatinib therapy: a single-center retrospective study].

Pulmonary artery hypertension (PAH) has been reported to be a severe adverse event associated with dasatinib therapy. Among the 76 chronic myeloid patients who were treated with dasatinib at our hospital, six patients showed high estimated pulmonary arterial systolic pressure, as observed by echocardiography. PAH was confirmed using right heart catheterization in three (3.9%) patients with increased mean pulmonary artery pressure (mPAP). In one patient, although mPAP was higher than the normal range, it did not fulfill the criteria of pulmonary hypertension. After the discontinuation of dasatinib, BNP and dyspnea were improved in five patients. Therefore, it should be noted that dasatinib can cause PAH at higher rates than those reported previously, and if PAH is confirmed or suspected during dasatinib therapy, then dasatinib should be immediately discontinued.

Upper-extremity Deep Vein Thrombosis Complicating Apheresis in a Healthy Donor.

Venous thrombus was recognized in the upper extremity of a 53-year-old man after blood donation. The patient presented with a 15-day history of swelling in the left upper-extremity that started 6 hours after apheresis. Contrast-enhanced computed tomography revealed clots in the deep veins of the left arm and the peripheral pulmonary artery. Blood donation had proceeded smoothly, and the patient had no thrombotic predisposition, except for a smoking habit. The thrombus resolved following anticoagulant therapy, and the patient' s clinical course was uncomplicated. Despite a thorough investigation, the cause of this thrombus remains unknown.

Successful Treatment of Congestive Heart Failure Due to Severe Aortic Valve Stenosis With Low Dose Tolvaptan in Elderly Patients.

Medical therapy for severe aortic valve stenosis (AS) is necessary for inoperable patients due to comorbid conditions. Tolvaptan (TLV), unlike other diuretics, resulted in modest changes in filling pressures associated with an increase in urine output, suggesting that TLV improves congestive heart failure (CHF) due to severe AS without hemodynamic instability.We retrospectively investigated 14 consecutive patients ≥ 80 years of age admitted due to decompensated CHF with severe AS at Juntendo University Hospital from April 2014 to November 2015. Seven of the 14 patients were treated with TLV. We examined the safety and efficacy of TLV treatment for severe AS.Mean age was 90.0 ± 6.3 years and mean aortic valve area was 0.57 ± 0.22 cm2. Urine volume at day 1 of TLV treatment was increased and urine osmolality significantly decreased at day 1 of TLV treatment (all P < 0.05). New York Heart Association classification and brain natriuretic peptide levels significantly improved 1 week after treatment and at discharge (all P < 0.05) whereas brain natriuretic peptide levels did not improve in the patients without TLV. Severe adverse events did not occur during TLV treatment. During the first 3 days, blood pressure and heart rate were relatively stable. TLV treatment did not affect serum creatinine, blood urea nitrogen, or the estimated glomerular filtration rate.In elderly patients with severe AS, TLV treatment improved CHF without hemodynamic instability. Further prospective studies are needed to assess the safety and efficacy of TLV in decompensated heart failure due to severe AS.

Significance of Serum Polyunsaturated Fatty Acid Level Imbalance in Patients with Acute Venous Thromboembolism.

AIM: Polyunsaturated fatty acids (PUFAs) take part in various biological events linked to the pathogenesis of venous thromboembolism (VTE), including inflammation, endothelial dysfunction, and hypercoagulability. Several studies have demonstrated the association between PUFAs and the occurrence of VTE. However, the role of PUFAs in the pathogenesis of VTE remains unclear. METHODS: We enrolled 45 patients with acute VTE and 37 age-, gender-, and body mass index-matched healthy volunteers to examine their PUFA levels. Serum omega 3 (eicosapentaenoic acid: EPA and docosahexaenoic acid: DHA) and omega 6 (dihomogammalinolenic acid: DGLA and arachidonic acid: AA) fatty acids levels were measured within 24 h of admission. RESULTS: Patients with VTE showed significantly higher AA and lower EPA levels, and lower EPA/AA ratios than the controls. Multivariate analysis revealed that AA was an independent marker for VTE. In addition, we divided the patients based on their median age (58 years old). The younger patients with VTE showed significantly lower EPA/AA levels than their age-matched controls, whereas older patients with VTE showed a significantly higher AA/DGLA levels than the older controls. CONCLUSIONS: High serum AA levels and low EPA levels are associated with the development of acute VTE, suggesting that the imbalance of PUFAs may be a potential therapeutic target for preventing acute VTE.

Deletion of LR11 Attenuates Hypoxia-Induced Pulmonary Arterial Smooth Muscle Cell Proliferation With Medial Thickening in Mice.

OBJECTIVE: We aimed to determine whether LR11 (low-density lipoprotein receptor with 11 binding repeats) is a potential key regulator of smooth muscle cell (SMC) proliferation during the progression of hypoxia-induced medial thickening in mice and whether sLR11 (soluble LR11) can serve as a biomarker in patients with pulmonary arterial hypertension. APPROACH AND RESULTS: The role of LR11 in pulmonary arterial hypertension was investigated using mouse and cell models of induced hypoxia. The expression of LR11 and of hypoxia-inducible factor-1α was significantly increased in lung tissues from C57Bl/6 mice after 3 weeks of exposure to hypoxia compared with normoxia. Serum sLR11 levels were also increased. Physiological and histochemical analyses showed that increased right ventricular systolic pressure, right ventricular hypertrophy, and medial thickening induced under hypoxia in wild-type mice were attenuated in LR11(-/-) mice. The proliferation rates stimulated by hypoxia or platelet-derived growth factor-BB were attenuated in SMC derived from LR11(-/-) mice, compared with those from wild-type mice. Exogenous sLR11 protein increased the proliferation rates of SMC from wild-type mice. The expression of LR11 and hypoxia-inducible factor-1α was increased in cultured SMC under hypoxic conditions, and hypoxia-inducible factor-1α knockdown almost abolished the induction of LR11. Serum sLR11 levels were significantly higher in patients with, rather than without, pulmonary arterial hypertension. sLR11 levels positively correlated with pulmonary vascular resistance and mean pulmonary arterial pressure. CONCLUSIONS: LR11 regulated SMC proliferation during the progression of hypoxia-induced medial thickening in mice. The findings obtained from mice, together with those in humans, indicate that sLR11 could serve as a novel biomarker that reflects the pathophysiology of proliferating medial SMC in pulmonary arterial hypertension.

Prognostic impact of chronic kidney disease on 10-year clinical outcomes among patients with acute coronary syndrome.

BACKGROUND: Chronic kidney disease (CKD) is closely associated with a higher risk of cardiovascular disease. However, whether patients with acute coronary syndrome (ACS) and CKD are at increased risk for long-term mortality after coronary revascularization remains unknown. METHODS AND RESULTS: Data from consecutive patients with ACS who had undergone coronary revascularization, including percutaneous coronary intervention (PCI) and coronary artery bypass surgery (CABG) were analyzed. The estimated glomerular filtration rate (eGFR) was calculated using the current Japanese equation and CKD was defined as eGFR < 60 mL/min/1.73 m(2). Among 375 enrolled patients with ACS, 75 (20.0%) had CKD. During a follow-up period of 10.0 ± 3.4 years, the total number of deaths was 80 (21.3%), of which 36 (9.6%) were due to cardiovascular causes. Kaplan-Meier analysis showed that the presence of CKD was associated with a significant increase in mortality from all causes (log-rank test, p<0.001) and cardiovascular mortality (p<0.001). Cox proportional-hazard analysis revealed that CKD increased the risk of mortality with a hazard ratio of 2.31 (95% confidence interval (CI): 1.25-4.29, p=0.008) and of cardiovascular death with a hazard ratio of 3.76 (95% CI: 1.60-8.80, p=0.002) in patients with ACS. CONCLUSIONS: CKD is a powerful determinant of long-term all-cause and cardiovascular mortality after ACS.