The NO-cGMP-PKG Axis in HFpEF: From Pathological Mechanisms to Potential Therapies.

Heart failure with preserved ejection fraction (HFpEF) accounts for almost half of all heart failure (HF) cases worldwide. Unfortunately, its incidence is expected to continue to rise, and effective therapy to improve clinical outcomes is lacking. Numerous efforts currently directed towards the pathophysiology of human HFpEF are uncovering signal transduction pathways and novel therapeutic targets. The nitric oxide-cyclic guanosine phosphate-protein kinase G (NO-cGMP-PKG) axis has been described as an important regulator of cardiac function. Suppression of the NO-cGMP-PKG signalling pathway is involved in the progression of HFpEF. Therefore, the NO-cGMP-PKG signalling pathway is a potential therapeutic target for HFpEF. In this review, we aim to explore the mechanism of NO-cGMP-PKG in the progression of HFpEF and to summarize potential therapeutic drugs that target this signalling pathway.

Allergic bronchopulmonary aspergillosis with marked peripheral blood eosinophilia and pulmonary eosinophilia: A case report.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is an immune-related pulmonary disease caused by sensitization of airway by Aspergillus fumigatus. The disease manifests as bronchial asthma and recurring pulmonary shadows, which may be associated with bronchiectasis. The diagnosis of ABPA mainly depends on serological, immunological, and imaging findings. Pathological examination is not necessary but may be required in atypical cases to exclude pulmonary tuberculosis, tumor, and other diseases through lung biopsy. CASE SUMMARY: An 18-year-old man presented with recurrent wheezing, cough, and peripheral blood eosinophilia. Chest computed tomography showed pulmonary infiltration. There was a significant increase in eosinophils in bronchoalveolar lavage fluid. There was no history of residing in a parasite-endemic area or any evidence of parasitic infection. Pathologic examination of bronchoalveolar lavage fluid excluded fungal and mycobacterial infections. The patient was receiving medication for comorbid diseases, but there was no temporal correlation between medication use and clinical manifestations, which excluded drug-induced etiology. Histopathological examination of lung biopsy specimen showed no signs of eosinophilic granulomatosis with polyangiitis, IgG4-related diseases, or tumors. The diagnosis of ABPA was considered based on the history of asthma and the significant increase in serum Aspergillus fumigatus-specific immunoglobulin (Ig)E. Eosinophil-related diseases were excluded through pathological biopsy, which showed typical pathological manifestations of ABPA. CONCLUSION: The possibility of ABPA should be considered in patients with poorly controlled asthma, especially those with eosinophilia, lung infiltration shadows, or bronchiectasis. Screening for serum IgE, Aspergillus fumigatus-specific IgE and IgG, and alveolar lavage can help avoid misdiagnosis.

Development and Validation of Predictive Model-HASBLAD Score-For Major Adverse Cardiovascular Events During Perioperative Period of Non-cardiac Surgery: A Single Center Experience in China.

Background: Major adverse cardiovascular events (MACEs) represent a significant reason of morbidity and mortality in non-cardiac surgery during perioperative period. The prevention of perioperative MACEs has always been one of the hotspots in the research field. Current existing models have not been validated in Chinese population, and have become increasingly unable to adapt to current clinical needs. Objectives: To establish and validate several simple bedside tools for predicting MACEs during perioperative period of non-cardiac surgery in Chinese hospitalized patients. Design: We used a nested case-control study to establish our prediction models. A nomogram along with a risk score were developed using logistic regression analysis. An internal cohort was used to evaluate the performance of discrimination and calibration of these predictive models including the revised cardiac risk index (RCRI) score recommended by current guidelines. Setting: Peking University Third Hospital between January 2010 and December 2020. Patients: Two hundred and fifty three patients with MACEs and 1,012 patients without were included in the training set from January 2010 to December 2019 while 38,897 patients were included in the validation set from January 2020 and December 2020, of whom 112 patients had MACEs. Main Outcome Measures: The MACEs included the composite outcomes of cardiac death, non-fatal myocardial infarction, non-fatal congestive cardiac failure or hemodynamically significant ventricular arrhythmia, and Takotsubo cardiomyopathy. Results: Seven predictors, including Hemoglobin, CARDIAC diseases, Aspartate aminotransferase (AST), high Blood pressure, Leukocyte count, general Anesthesia, and Diabetes mellitus (HASBLAD), were selected in the final model. The nomogram and HASBLAD score all achieved satisfactory prediction performance in the training set (C statistic, 0.781 vs. 0.768) and the validation set (C statistic, 0.865 vs. 0.843). Good calibration was observed for the probability of MACEs in the training set and the validation set. The two predictive models both had excellent discrimination that performed better than RCRI in the validation set (C statistic, 0.660, P < 0.05 vs. nomogram and HASBLAD score). Conclusion: The nomogram and HASBLAD score could be useful bedside tools for predicting perioperative MACEs of non-cardiac surgery in Chinese hospitalized patients.

Peri-operative Takotsubo syndrome after non-cardiac surgery: a retrospective nested case-control study.

AIMS: Takotsubo syndrome (TTS) is an acute reversible cardiac dysfunction that may occur during the peri-operative period and among patients with serious illness. We aimed to evaluate the clinical characteristics, peri-operative management, and prognosis of peri-operative TTS (pTTS) and explore the factors associated with pTTS. METHODS: We conducted a retrospective nested case-control study using the database of patients who underwent in-hospital non-cardiac surgeries between January 2017 and December 2020 in Peking University Third hospital. Cases were adult patients diagnosed TTS at discharge who were matched with four controls based on operative types. Multivariable conditional logistic regression was used to identified the factors associated with pTTS. The area under the curve (AUC) was used to evaluate the diagnostic efficacy. RESULTS: Among the 128 536 patients underwent non-cardiac surgery, 20 patients with pTTS and 80 patients without were enrolled in this study. The incidence of pTTS was about 0.016% in our centre. The median age of patients with pTTS was 52.5 (38.25, 76.25) years, although 90% of them were female. Fifty per cent (9 cases) of female patients were pre-menopausal. Caesarean section has the highest proportion of pTTS (30% of the pTTS cases) with the incidence of caesarean section-related pTTS of 0.06% in our centre. A high prevalence of non-apical ballooning pattern of regional wall motion abnormality (seven cases, 35%) and a high mortality (two cases, 10%) were observed. Left ventricular ejection fraction (LVEF) of patients with pTTS was significantly decreased (41.7 ± 8.8%). In the acute phase, supportive treatments aiming to reduce life-threatening complications were main treatment strategies. After receiving systematic treatment, significant improvements were observed in LVEF (63.1 ± 13.5%), with median recovery time of LVEF of 7.48 days. Leucocyte count [odds ratio (OR): 4.59; 95% confidence interval (CI): 1.10-19.15], haemoglobin (HGB) (OR: 10.52; 95% CI: 1.04-106.36), and the revised cardiac risk index (RCRI) score (OR: 6.30; 95% CI: 1.05-37.88) were the factors significantly associated with pTTS. The RCRI score performed poorly in the prediction of pTTS (AUC: 0.630; 95% CI: 0.525-0.735). After adding leucocyte count and HGB into the RCRI score, the AUC was significantly improved (AUC: 0.768; 95% CI: 0.671-0.865; P = 0.001). CONCLUSIONS: Patients with pTTS have some differences compared with common TTS, including higher proportion of pre-menopausal female, higher prevalence during caesarean section, higher prevalence of non-apical ballooning pattern of regional wall motion abnormality, and higher mortality. The RCRI score performed poorly in the evaluation of pTTS. Adding HGB and leucocyte count into the RCRI score could significantly improve its predictive performance.

Short-term exposure to traffic-related air pollution and STEMI events: Insights into STEMI onset and related cardiac impairment.

AIMS: Evidence on the impacts of traffic-related air pollution (TRAP) on ST-segment elevation myocardial infarction (STEMI) events is limited. We aimed to assess the acute effects of TRAP exposure on the clinical onset of STEMI and related cardiac impairments. METHODS AND RESULTS: We recruited patients who were admitted for STEMI and underwent primary percutaneous coronary intervention at Peking University Third Hospital between 2014 and 2020. Indicators relevant to cardiac impairments were measured. Concomitantly, hourly concentrations of traffic pollutants were monitored throughout the study period, including fine particulate matter, black carbon (BC), particles in size ranges of 5-560 nm, oxides of nitrogen (NOX), nitrogen dioxide, and carbon monoxide. The mean (SD) age of participants was 62.4 (12.5) years. Daily average (range) concentrations of ambient BC and NOX were 3.9 (0.1-25.0) µg/m3 and 90.8 (16.6-371.7) µg/m3. Significant increases in STEMI risks of 5.9% (95% CI: 0.1, 12.0) to 21.9% (95% CI: 6.0, 40.2) were associated with interquartile range increases in exposure to TRAP within a few hours. These changes were accompanied by significant elevations in cardiac troponin T levels of 6.9% (95% CI: 0.2, 14.1) to 41.7% (95% CI: 21.2, 65.6), as well as reductions in left ventricular ejection fraction of 1.5% (95% CI: 0.1, 2.9) to 3.7% (95% CI: 0.8, 6.4). Furthermore, the associations were attenuated in participants living in areas with higher residential greenness levels. CONCLUSIONS: Our findings extend current understanding that short-term exposure to higher levels of traffic pollution was associated with increased STEMI risks and exacerbated cardiac impairments, and provide evidence on traffic pollution control priority for protecting vulnerable populations who are at greater risks of cardiovascular events.