Pulmonary Hypertension Caused by Fibrosing Mediastinitis.

Pulmonary hypertension (PH) is a progressive and severe disorder in pulmonary hemodynamics. PH can be fatal if not well managed. Fibrosing mediastinitis (FM) is a rare and benign fibroproliferative disease in the mediastinum, which may lead to pulmonary vessel compression and PH. PH caused by FM (PH-FM) is a pathologic condition belonging to group 5 in the World Health Organization PH classification. PH-FM has a poor prognosis because of a lack of effective therapeutic modalities and inappropriate diagnosis. With the development of percutaneous pulmonary vascular interventional therapy, the prognosis of PH-FM has been greatly improved in recent years. This article provides a comprehensive review on the epidemiology, pathophysiologic characteristics, clinical manifestations, diagnostic approaches, and treatment modalities of PH-FM based on data from published reports and our medical center with the goal of facilitating the diagnosis and treatment of this fatal disease.

Clinical Efficacy of Catheter Ablation in the Treatment of Vasovagal Syncope.

Catheter ablation of ganglionated plexi (GPs) performed as cardioneuroablation in the left atrium (LA) has been reported previously as a treatment for vasovagal syncope (VVS). However, the efficacy and safety of catheter ablation in the treatment of VVS remains unclear. The objective of this study is to explore the efficacy and safety of catheter ablation in the treatment of VVS and to compare the different ganglion-mapping methods for prognostic effects. A total of 108 patients with refractory VVS who underwent catheter ablation were retrospectively enrolled. Patients preferred to use high-frequency stimulation (HFS) (n = 66), and anatomic landmark (n = 42) targeting is used when HFS failed to induce a positive reaction. The efficacy of the treatment is evaluated by comparing the location and probability of the intraoperative vagal reflex, the remission rate of postoperative syncope symptoms, and the rate of negative head-up tilt (HUT) results. Adverse events are analyzed, and safety is evaluated. After follow-up for 8 (5, 15) months, both HFS mapping and anatomical ablation can effectively improve the syncope symptoms in VVS patients, and 83.7% of patients no longer experienced syncope (<0.001). Both approaches to catheter ablation in the treatment of VVS effectively inhibit the recurrence of VVS; they are safe and effective. Therefore, catheter ablation can be used as a treatment option for patients with symptomatic VVS.

Spatiotemporally co-delivery of triple therapeutic drugs via HA-coating nanosystems for enhanced immunotherapy.

There is growing empirical evidence that certain types of chemotherapy and phototherapy trigger immunogenic cell death and enhance the therapeutic anticancer efficacy of genetic immunotherapy. However, the main challenge is spatiotemporally co-delivering different drugs to maximize the therapeutic index of the combination therapy. In this study, a drug delivery system (HTCP-Au/shPD-L1/DOX) was designed with a polysaccharide-wrapped shell and a condensed DNA core. To construct the HTCP-Au vector, dodecyl side chains with a polyethylenimine (PEI) head were grafted onto hyaluronic acid, and AuNPs were grafted via Au-S bonds. During drug loading, PEI arrested shRNA plasmid DNA targeting programmed cell death ligand 1 (shPD-L1) via electrostatic interactions. It also formed a PEI-DNA core that was automatically enclosed when aliphatic hydrocarbons pulled the hyaluronic acid backbone. A hydrophobic interlayer consisting of dodecyl bridge chains between the PEI-DNA core and the hyaluronic acid shell was required to accommodate hydrophobic doxorubicin. In vitro and in vivo assays demonstrated that this core-shell drug delivery system could efficiently load and transport three different drugs and effectively target tumors. Moreover, it could activate the immune system, thereby providing promising therapeutic efficacy against tumor growth and metastasis.

Prognostic implications of ST-segment elevation in lead aVR in patients with acute coronary syndrome: A meta-analysis.

BACKGROUND: ST-segment elevation (STE) in lead aVR is a useful tool in recognizing patients with left main or left anterior descending coronary obstruction during acute coronary syndrome (ACS). The prognostic implication of STE in lead aVR on outcomes has not been established. METHODS: We performed a systematic search for clinical studies about STE in lead aVR in four databases including PubMed, EMBASE, Cochrane Library, and Web of Science. Primary outcome was in-hospital mortality. Secondary outcomes included in-hospital (re)infarction, in-hospital heart failure, and 90-day mortality. RESULTS: We included 7 studies with a total of 7,700 patients. The all-cause in-hospital mortality of patients with STE in lead aVR during ACS was significantly higher than that of patients without STE (OR: 4.37, 95% CI 1.63 to 11.68, p = .003). Patients with greater STE (>0.1 mV) in lead aVR had a higher in-hospital mortality when compared to lower STE (0.05-0.1 mV) (OR: 2.00, 95% CI 1.11-3.60, p = .02), However, STE in aVR was not independently associated with in-hospital mortality in ACS patients (OR: 2.72, 95% CI 0.85-8.63, p = .09). The incidence of in-hospital myocardial (re)infarction (OR: 2.77, 95% CI 1.30-5.94, p = .009), in-hospital heart failure (OR: 2.62, 95% CI 1.06-6.50, p = .04), and 90-day mortality (OR: 10.19, 95% CI 5.27-19.71, p < .00001) was also noted to be higher in patients STE in lead aVR. CONCLUSIONS: This contemporary meta-analysis shows STE in lead aVR is a poor prognostic marker in patients with ACS with higher in-hospital mortality, reinfarction, heart failure and 90-day mortality. Greater magnitude of STE portends worse prognosis. Further studies are needed to establish an independent predictive role of STE in aVR for these adverse outcomes.

Clinical Features of Patients Undergoing the Head-Up Tilt Test and Its Safety and Efficacy in Diagnosing Vasovagal Syncope in 4,873 Patients.

Background: The head-up tilt test (HUTT) is a useful diagnostic tool in patients with suspected vasovagal syncope (VVS). Objectives: We aimed to investigate the direct drug-potentiated HUTT in patients with recurrent syncope or precursor syncope and to assess the diagnostic value of the direct drug-potentiated HUTT. Methods: The medical history and direct drug-potentiated HUTT records of patients who complained of syncope or precursor syncope and who visited The Xianyang Central Hospital from January 2016 to December 2020 were retrospectively reviewed. Results: A total of 4,873 patients (age = 43.8 ± 17.6 years; male = 2,064 [42.4%]) were enrolled in our study. Overall, 2,343 (48.1%) showed positive responses as follows: 1,260 (25.9%) with the mixed type, 34 (0.7%) with the cardioinhibitory type, 580 (11.9%) with the vasodepressor type, 179 (3.7%) with postural tachycardia syndrome (POTS), and 290 (6.0%) with orthostatic hypotension (OH). The study showed that prior to syncope or near-syncope symptoms, patients first presented an increase in heart rate (HR), followed by decreases in blood pressure (BP) and HR successively. Among the patients in the syncope group, the sensitivity of the HUTT was 65.9%, which was significantly higher than a sensitivity of 44.8% for patients in the non-syncope group (P < 0.01). The sensitivity of the HUTT was higher for females than males in both the syncope group (52.6% in males and 77.9% in females, P < 0.01) and the non-syncope group (36.5% in males and 50.6% in females, P < 0.01). Within the four age groups (<20, 21-40, 41-60, and >60 years old), the sensitivities were 74.7%, 67.7%, 45.6%, and 31.2%, respectively. And all gender, age and symptom (whether suffered from a syncope or not) significantly affected the positive responses of HUTT. There were two adverse events and no deaths during the HUTT in this study. Conclusion: The direct drug-potentiated HUTT is a safe and highly sensitive tool with which to diagnose VVS. Patients with precursor syncope symptoms without syncope should undergo a HUTT, especially young females presenting with weakness and sweating, which can decrease the probability of a misdiagnosis or a missed diagnosis.

A rare case of severe right heart failure due to pulmonary artery lymphomatoid granulomatosis.

Lymphomatoid granulomatosis is a rare, vascular-centric, and vessel-destroying lymphoproliferative disease that hardly involves the pulmonary arteries. Herein, we report a case with severe right heart failure and pulmonary arterial stenosis caused by pulmonary artery lymphomatoid granulomatosis. This case was diagnosed by percutaneous transluminal pulmonary artery biopsy and was effectively treated with stent implantation and steroid administration.

Meta-analysis of right ventricular function in patients with aortic stenosis after transfemoral aortic valve replacement or surgical aortic valve replacement.

BACKGROUND: Right ventricular function (RVF) is an independent predictor of prognosis for patients undergoing aortic valve replacement: transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR). The effect of transfemoral aortic valve replacement (TF-TAVR) on RVF is uncertain. We aimed to perform a meta-analysis of the effect of TF-TAVR on RVF in patients with aortic stenosis (AS) and compare the effect of TF-TAVR with SAVR. METHODS: We searched relevant studies from PubMed, Embase, Cochrane Library databases, and Web of Science. Furthermore, two reviewers (Wang AQ and Cao YS) extracted all relevant data, which were then double checked by another two reviewers (Zhang M and Qi GM). We used the forest plot to present results. Tricuspid annular plane systolic excursion (TAPSE) was the primary outcome. RESULTS: This meta-analysis included 11 studies. There were 353 patients who underwent TF-TAVR, and 358 patients who were subjected to SAVR. There was no significant difference in TAPSE at 1 week and 6 months as well as right ventricular ejection fraction (RVEF) at <2 weeks and 6 months after TF-TAVR. For the SAVR group, TAPSE at 1 week and 3 months as well as fractional area change (FAC) at 3 months post procedure were significantly aggravated, while RVEF did not change significantly. Moreover, TAPSE post-TF-TAVR was significantly improved as compared with post-SAVR. The △TAPSE, the difference between TAPSE post-procedure and TAPSE prior to procedure, was also significantly better in the TF-TAVR group than in the SAVR group. CONCLUSION: RVF was maintained post TF-TAVR. For SAVR, discrepancy in the measured parameters exists, as reduced TAPSE indicates compromised longitudinal RVF, while insignificant changes in RVEF implicate maintained RVF post procedure. Collectively, our study suggests that the baseline RV dysfunction and the effect of TF-TAVR versus SAVR on longitudinal RVF may influence the selection of aortic valve intervention.

RNA-sequencing analysis of gene expression in a rat model of acute right heart failure.

Background: Acute right heart failure (RHF) is the main cause of death in patients with acute pulmonary embolism and emergent pulmonary hypertension. However, the molecular mechanisms underpinning the acute RHF and the interactions between the right (RV) and left ventricles (LVs) under the diseased condition remain unknown. Methods and results: The Sprague Dawley male rats were randomly divided into the normal control, sham, and pulmonary artery banding (PAB) groups. One hour after the PAB operation, after measuring the haemodynamic and anatomical parameters, the free walls of RV and LV were harvested to detect the differential gene expression profiling by high-throughput RNA sequencing. The results showed that the PAB lead to 50-60% obstruction of the main pulmonary artery, which was accompanied by the significant elevation in the positive rate of rise in RV pressure and the maximum RV pressure as compared to the sham group. Moreover, compared with the counterparts in the sham group, the RV and LV in the PAB group exhibited 2057 differentially expressed genes (DEGs, 1159 upregulated and 898 downregulated) and 1196 DEGs (709 upregulated and 487 downregulated), respectively (DEG criteria: |log2 fold change| ≥1, q value ≤0.05). In comparison to the sham group, the enriched pathways in the PAB group include nuclear factor-κB signalling pathway, extracellular matrix-receptor interaction, and nucleotide oligomerization domain-like receptor signalling pathway. Conclusions: The PAB rat model exhibited the haemodynamic and gene expression changes in the RV that lead to acute RHF. Further, the acute RHF induced by pressure overload also caused gene expression changes in the LV, suggesting the molecular interactions between the RV and LV under the diseased condition.

Balloon angioplasty or stent implantation for pulmonary vein stenosis caused by fibrosing mediastinitis: a systematic review.

Fibrosing mediastinitis (FM) is a very rare disease, often caused by histoplasmosis capsulatum, tuberculosis, sarcoidosis, autoimmunity and other diseases, such as IgG 4-related diseases. Fibrous structures in the mediastinum compress the pulmonary artery, pulmonary vein, superior vena cava, esophagus, trachea and cardiac vessels, leading to clinical symptoms. Drug therapeutic modality for pulmonary vein stenosis (PVS) caused by FM is palliative in essence and with limited efficacy, whereas surgical treatment causes high mortality. In recent years, catheter-based treatment to FM-caused PVS has emerged as a promising therapeutic modality, however, the safety and effectiveness of this modality remain unclear. Therefore, a systematic review on the safety and efficacy of the catheter-based treatment for PVS caused by FM was performed, in the hope to shed lights on the alternative therapeutic strategy to this fatal disease.

Acute myocardial infarction and transient elevated anticardiolipin antibody in a young adult with possible familial hypercholesterolemia: a case report : Anticardiolipin antibody and myocardial infarction.

BACKGROUND: Familial hypercholesterolemia (FH) can lead to premature coronary heart disease. Anticardiolipin antibody may be a contributor for thrombosis. Here, we report an adult with possible FH suffered from premature myocardial infarction that may be triggered by transient increased anticardiolipin antibody. CASE PRESENTATION: A 29-year-old male had presented with a history of 2-h chest pain and numbness of left upper arm before 5 days. The electrocardiogram (ECG) had demonstrated inferior wall myocardial infarction (MI). Five days later he was admitted to our hospital and diagnosed as acute MI and possible FH (premature coronary heart disease, low density lipoprotein cholesterol of 5.90 mmol/L) with increased anticardiolipin antibody (up to 120 RU/ml). Other auto-antibodies including ß2-glicoprotein antibodies IgM, IgA, IgG, lupus anticoagulant (LA), antinuclear antibodies, anti-myocardial antibody were normal. Coronary artery angiography (CAG) showed right coronary artery was total occlusion from the middle segment. Then he underwent percutaneous coronary intervention with a stent. Four days later, he was discharged with complete recovery. CAG showed intra-stent restenosis and anticardiolipin antibody level was normal and the patient had no any symptoms at 6-month follow-up. CONCLUSIONS: Transient elevated anticardiolipin antibody may be a trigger or biomarker of cardiac thrombotic events in younger atherosclerotic patients.

Autologous bone marrow stem cell therapy for patients undergoing coronary artery bypass grafting: A meta-analysis of 14 randomized controlled trials.

Autologous bone marrow stem cell (BMSC) therapy is a novel option for regenerative therapy in patients with ischemic heart disease. The aim of the present meta-analysis was to evaluate the effectiveness of BMSCs combined with coronary artery bypass grafting (CABG). The PubMed, Cochrane Library, EMBASE and Web of Science databases were searched from inception to November 22, 2017 for randomized controlled trials on BMSC therapy combined with CABG. Finally, 14 trials with a total of 596 participants were included. Data were analyzed using a random-effects model. Compared with the control group, the BMSC therapy group exhibited an improvement in the left ventricular (LV) ejection fraction from baseline to follow-up [mean difference (MD)=4.36%; 95% confidence interval (CI): 1.90-6.81%; P<0.01]. Analysis of the pooled results revealed non-significant differences in the LV end-diastolic volume (MD=-6.27 ml; 95% CI: -22.34 to 9.80 ml; P=0.44), LV end-diastolic volume index (MD=-15.11 ml/m2; 95% CI: -31.53 to 1.30 ml/m2; P=0.07), LV end-systolic volume (MD=-11.52 ml; 95% CI: -26.97 to 3.93 ml; P=0.14) and LV end-systolic volume index (MD=-16.56 ml/m2; 95% CI: -37.75 to 4.63 ml/m2; P=0.13) between the BMSC and CABG alone groups. Therefore, autologous BMSC therapy for patients undergoing CABG appears to be associated with an improvement in LV function compared with CABG alone.