Pathogenesis of pulmonary hypertension caused by left heart disease.

Pulmonary hypertension has high disability and mortality rates. Among them, pulmonary hypertension caused by left heart disease (PH-LHD) is the most common type. According to the 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension, PH-LHD is classified as group 2 pulmonary hypertension. PH-LHD belongs to postcapillary pulmonary hypertension, which is distinguished from other types of pulmonary hypertension because of its elevated pulmonary artery wedge pressure. PH-LHD includes PH due to systolic or diastolic left ventricular dysfunction, mitral or aortic valve disease and congenital left heart disease. The primary strategy in managing PH-LHD is optimizing treatment of the underlying cardiac disease. Recent clinical studies have found that mechanical unloading of left ventricle by an implantable non-pulsatile left ventricular assist device with continuous flow properties can reverse pulmonary hypertension in patients with heart failure. However, the specific therapies for PH in LHD have not yet been identified. Treatments that specifically target PH in LHD could slow its progression and potentially improve disease severity, leading to far better clinical outcomes. Therefore, exploring the current research on the pathogenesis of PH-LHD is important. This paper summarizes and classifies the research articles on the pathogenesis of PH-LHD to provide references for the mechanism research and clinical treatment of PH-LHD, particularly molecular targeted therapy.

Protein-enriched extracts from housefly (Musca domestica) maggots alleviates atherosclerosis in apolipoprotein E-deficient mice by promoting bile acid production and consequent cholesterol consumption.

Currently, atherosclerosis control is important to prevent future heart attacks or strokes. Protein-enriched extract (PE) from housefly maggots (Musca domestica) can inhibit the development of atherosclerosis partially through its antioxidant effects. Whether PE exerts other anti-atherosclerosis functions remains unclear. Here, PE was found to simultaneously promote cholesterol metabolism effects in apolipoprotein E knockout (ApoE-/- ) mice. Bile acid synthesis plays a key role in regulating cholesterol homeostasis in atherosclerosis. Whether PE alleviates atherosclerosis by promoting bile acid production and consequent cholesterol consumption was further explored. First, 8-week-old male ApoE-/- mice were recruited and fed on a cholesterol-enriched diet. After 8 weeks, these mice were divided into three groups and received gavage administration of PE, simvastatin, and saline for another 8 weeks. Atherosclerosis severity was then assessed. Real-time quantitative polymerase chain reaction and western blot were employed to determine the expression of hepatic ATP-binding cassette transporter A1 (ABCA1), liver X receptor α (LXRα), and peroxisome proliferator-activated receptor-γ (PPAR-γ). Serum levels of high-density lipoprotein-cholesterol (HDL), low-density lipoprotein-cholesterol (LDL), and total cholesterol (TC) were determined by enzyme-linked immunoassay. Results revealed that PE reversed the formation of atherosclerotic lesion; increased the expression of PPAR-γ, LXRα, and ABCA1; increased the amount of bile flow and total bile acid; reduced the serum level of LDL and TC; and increased the level of HDL. In conclusion, enhancement on bile acid production and consequent cholesterol consumption may partially contribute to the anti-atherosclerotic effects of PE. The reversal of PPARγ-LXRα-ABCA1 signaling pathway may be involved in this process.

Circulating long non-coding RNA TTTY15 and HULC serve as potential novel biomarkers for predicting acute myocardial infarction.

INTRODUCTION: Acute myocardial infarction (AMI) is a ubiquitous cardiovascular disease ensuing adverse prognosis caused by myocardial necrosis. Effective and rapid diagnosis of AMI is essential to following treatment in clinical practice while the existed biomarkers have inherent limitations. Consequently, exploration of novel biomarkers is needed. Long noncoding RNA (lncRNA) emerges as the upcoming biomarkers adopted in clinical use, and we aim at investigating the diagnostic power of lncRNA TTTY15 and HULC in AMI patients. METHOD: We measured lncRNA level in 80 AMI patients and 36 healthy volunteers in discovering cohort and 50 AMI patients and 20 healthy volunteers in verification cohort with quantitative RT-PCR method. Receiver operating characteristic (ROC) analysis was administered to detect the diagnostic power of selected lncRNAs. Regression and correlation analyses were performed to explore the related factors. RESULTS: ROC analysis reveals the superiority of TTTY15 and HULC as biomarkers against conventional AMI biomarkers CKMB (AUC of TTTY15: 0.915 versus CKMB: 0.768 versus TnT: 0.869); AUC of HULC: 0.905 versus CKMB: 0.768 versus TnT: 0.869). Regression and correlation analysis indicates that TTTY15 and HULC may be one of the contributing factors to AMI and related to accepted risk factors. CONCLUSION: Our results revealed the diagnostic potency of lncRNA TTTY15 and HULC, and they could also be treated as novel therapeutic targets in AMI therapy, hinting inspiration to the cardiologist in clinical practice.

Prevalence and Prognosis of HFimpEF Developed From Patients With Heart Failure With Reduced Ejection Fraction: Systematic Review and Meta-Analysis.

Background: Heart failure with improved ejection fraction (HFimpEF) is classified as a new type of heart failure, and its prevalence and prognosis are not consistent in previous studies. There is no systematic review and meta-analysis regarding the prevalence and prognosis of the HFimpEF. Method: A systematic search was performed in MEDLINE, EMBASE, and Cochrane Library from inception to May 22, 2021 (PROSPERO registration: CRD42021260422). Studies were included for analysis if the prognosis of mortality or hospitalization were reported in HFimpEF or in patients with heart failure with recovered ejection fraction (HFrecEF). The primary outcome was all-cause mortality. Cardiac hospitalization, all-cause hospitalization, and composite events of mortality and hospitalization were considered as secondary outcomes. Result: Nine studies consisting of 9,491 heart failure patients were eventually included. During an average follow-up of 3.8 years, the pooled prevalence of HFimpEF was 22.64%. HFimpEF had a lower risk of mortality compared with heart failure patients with reduced ejection fraction (HFrEF) (adjusted HR: 0.44, 95% CI: 0.33-0.60). HFimpEF was also associated with a lower risk of cardiac hospitalization (HR: 0.40, 95% CI: 0.20-0.82) and the composite endpoint of mortality and hospitalization (HR: 0.56, 95% CI: 0.44-0.73). Compared with patients with preserved ejection fraction (HFpEF), HFimpEF was associated with a moderately lower risk of mortality (HR: 0.42, 95% CI: 0.32-0.55) and hospitalization (HR: 0.73, 95% CI: 0.58-0.92). Conclusion: Around 22.64% of patients with HFrEF would be treated to become HFimpEF, who would then obtain a 56% decrease in mortality risk. Meanwhile, HFimpEF is associated with lower heart failure hospitalization. Further studies are required to explore how to promote left ventricular ejection fraction improvement and improve the prognosis of persistent HFrEF in patients. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021260422, identifier: CRD42021260422.

Trends in incidence and long-term prognosis of acute kidney injury following coronary angiography in Chinese cohort with 11,943 patients from 2013 to 2017: an observational study.

BACKGROUND: Contrast-associated acute kidney injury (CA-AKI) is a common complication with poor prognosis after coronary angiography (CAG). With the prevention methods widely being implemented, the temporal trends of incidence and mortality of CA-AKI are still unknown over the last five years. The study aims to determine the incidence and prognosis of CA-AKI in China. METHODS: This retrospective cohort study was based on the registry at Guangdong Provincial People's Hospital in China (ClinicalTrials.gov NCT04407936). We analyzed data from hospitalization patients who underwent CAG and with preoperative and postoperative serum creatinine (Scr) values from January 2013 to December 2017. RESULTS: 11,943 patients were included in the study, in which the mean age was 63.01 ± 10.79 years and 8,469 (71.1 %) were male. The overall incidence of CA-AKI was 11.2 %. Compared with 2013, the incidence of CA-AKI in 2017 was significantly increased from 9.7 to 13.0 % (adjusted odds ratios [aOR], 1.38; 95 %CI, 1.13-1.68; P-value < 0.01, P for trend < 0.01). The temporal trends of incidence among patients of different ages and genders yielded similar findings. During a standardized follow-up of 1 year, 178 (13.7 %) CA-AKI patients died in total, which showed no obvious decreased trend in this 5 five years from 21.1 to 16.5 (adjusted hazard ratio [aHR], 0.72; 95 %CI, 0.36-1.45; P-value = 0.35, P for trend = 0.24). CONCLUSIONS: Our Chinese cohort showed that the incidence of CA-AKI increased significantly, while CA-AKI associated mortality showed no obvious decreased trend in the last five years. Our findings support more active measures to prevent CA-AKI and improve the prognosis of CA-AKI patients.

Association of dialysis-requiring acute kidney injury with 90-day prognosis in patients with coronary artery disease and advanced kidney disease after coronary angiography.

BACKGROUND: Dialysis-requiring acute kidney injury (AKI-D) is a potentially serious complication associated with high in-hospital mortality among patients with coronary artery disease (CAD) after coronary angiography (CAG). Patients with existing advanced kidney disease (AKD) have an increased risk of developing AKI-D. However, few studies have investigated the prognosis of AKI-D in patients with both CAD and AKD. METHODS: In this observational study, 603 CAD patients with AKD (estimated glomerular filtration rate, eGFR <30 mL/min/1.73 m2) were enrolled. AKI-D was defined as acute or worsening renal failure requiring the initiation of renal dialysis. The primary endpoint was 90-day all-cause mortality. Kaplan-Meier and Cox regression analyses were used to assess the association of AKI-D and 90-day all-cause mortality among CAD patients complicated with AKD. RESULTS: Overall, among 603 CAD patients complicated with AKD, 83 patients (13.8%) required AKI-D. Patients underwent AKI-D had a significantly higher rate of 90-day mortality than those who did not (13.3% vs. 6.5%, log rank P=0.028), with an unadjusted hazard ratio (HR) of 1.28 [95% confidence interval (CI): 1.02-1.61, P=0.032]. After adjustment for cardiac and renal impairment, however, AKI-D was no longer associated with 90-day mortality (HR: 1.08, 95% CI: 0.84-1.39, P=0.559). The attenuation analysis showed that after adjustment for cardiac and renal function, the residual effect of 90-day mortality was as low as 30% of the unadjusted effect. CONCLUSIONS: The incidence of AKI-D is high among patients with CAD complicated by AKD. The high 90-day mortality rate of patients undergoing AKI-D is mainly attributable to cardio-renal impairment.