Cardiology Research and Practice

Vascular calcification (VC) has a high incidence in patients with chronic kidney disease, which is a worldwide public health problem and presents a heavy burden to society. Hypoxia-inducible factor (HIF)-1α, the active subunit of HIF-1, has been reported to play a vital role in high phosphate-induced VC. However, the underlying mechanism is still undetermined, and effective treatment is unavailable. In the present study, human aortic smooth muscle cells (HASMCs) were cultured under normal or high phosphate media conditions. HIF-1α small interfering RNA and overexpression plasmids were employed to regulate HIF-1α expression. Phosphonoformic acid was employed to restrain the function of type III sodium-dependent phosphate cotransporter 1 (Pit-1). The expression levels of HIF-1α, Pit-1, runt-related transcription factor 2 (Runx2), and smooth muscle 22 alpha (SM22α) were evaluated, and the calcium contents were also examined. Cell growth was assessed using an MTT assay. High phosphate stimulation caused an upregulation in HIF-1α and Pit-1 expression levels and induced calcium depositions in HASMCs. Upregulation of Runx2 expression accompanied by downregulation of SM22α expression was observed in the high phosphate group. Following the suppression of HIF-1α expression, there was a concomitant attenuation in Pit-1 expression, calcium deposition, the alteration of phenotypic transition marker genes, and vice versa. The most serious calcium deposition was noted in HASMCs cultured under high phosphate conditions which were pretreated with a HIF-1α overexpression plasmid. However, when the biological functions of Pit-1 were restrained, the putative serious calcium deposition was not formed even in HASMCs transfected with a HIF-1α overexpression plasmid. The findings confirmed that HIF-1α regulated Pit-1 expression and exerted its pro-calcifying effect through Pit-1, which identified HIF-1α and Pit-1 as therapeutic targets for high phosphate-induced VC.

Background. Coronary heart disease (CHD) is the leading cause of death and disability worldwide. Accumulating evidence reveals that atherosclerosis (AS), characterized by systemic, chronic, and multifocal disease, and is the primary pathological basis of cardiovascular diseases, including CHD. However, the molecular underpinnings of CHD are still far from well understood. Our study attempted to identify aberrant plasma exosome-derived circRNAs and key exosomal circRNA biomarkers for CHD. Methods. The expression profiles of mRNAs, circRNAs, and lncRNAs in the blood exosomes of CHD patients and healthy controls were obtained from the exoRBase database. The corresponding miRNAs of the differentially expressed mRNAs, circRNAs, and lncRNAs were predicted via ENCORI and the miRcode database. LncRNAs/circRNAs and mRNAs with the cotargeted miRNAs were selected to construct an interaction network. Multiple machine learning algorithms have been used to explore potential biomarkers, followed by verification in patients with CHD using real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Results. Based on the cutoff criterion of , we identified 85 differentially expressed circRNAs (4 upregulated and 81 downregulated), 43 differentially expressed lncRNAs (24 upregulated and 19 downregulated), and 312 differentially expressed mRNAs (55 upregulated and 257 downregulated). Functional enrichment analysis revealed that the differentially expressed mRNAs were involved mainly in neutrophil extracellular trap (NET) formation and the nucleotide-binding oligomerization domain- (NOD-) like receptor signaling pathway. Further analysis revealed that the DEGs in the circRNA/lncRNA-miRNA-mRNA interaction network were closely related to lipid and atherosclerotic signaling pathways. Hsa_circ_0001360 and hsa_circ_0000038 were identified as potential biomarkers for CHD based on three machine learning algorithms. The relative expression levels of hsa_circ_0001360 and hsa_circ_0000038 were significantly altered in plasma exosomes from patients with CHD. ROC curve analysis revealed that the areas under the curve (AUCs) were 0.860, 0.870, and 0.940 for hsa_circ_0001360, hsa_circ_0000038, and the two-gene combination, respectively. Conclusion. The circRNA/lncRNA-miRNA-mRNA interaction network might help to elucidate the pathogenesis of CHD. Hsa_circ_0001360 combined with hsa_circ_0000038 might be an important diagnostic biomarker.

Objectives. To examine the relationship of QRS voltages and left ventricular (LV) mass across the spectrum of individuals with different LV mass. Methods. Twenty QRS voltage measurements or combinations were determined in a consecutive series of 159 adults with an ECG and echocardiogram without previous myocardial infarction, left or right bundle branch block, pre-excitation, or electronic pacemaker. Results. The four strongest and significant correlations between QRS and LV mass were S in V4, deepest S wave in any precordial lead plus S in V4, S in V3, and S in V3 plus R in AVL times QRS duration. For men, the strength of the relationships were S in V3 (F = 33.8), deepest S wave in any precordial lead plus S V4 (F = 33.7), S in V3 plus R aVL (F = 29.9), S in V4 (F = 29.79), and deepest S in precordial leads (F = 17.9). The R wave in AVL alone did not correlate with LV mass. Criteria using the R wave in lateral precordial leads did not correlate as strongly with LV mass. For women, only S in V4 significantly correlated with LV mass. Overall, the R wave voltage in limb leads (AVL I or II) did not correlate with precordial S wave amplitudes. Univariate and multivariate analysis showed that some but not all QRS voltages correlated with each other. In multivariate analysis, using only single variables and not combination of QRS variables, the only significant relationship between QRS voltage and left ventricular mass was for men the S in V3 () and for women S in V4 () and R in V6 (). Conclusion. The S wave in V3 and V4 correlate most strongly with LV mass while the R wave in limb leads, including AVL, do not correlate.

Background. Nepal, currently facing a high burden of noncommunicable diseases (NCDs), including cardiovascular diseases (CVDs), which poses the highest mortality rate in the country, does not seem to have a proper referral strategy. This study explored the wide range of factors and challenges that affect the referral system of CVD cases in Nepal. Methods. In this qualitative study, we conducted face-to-face and telephone interviews with purposely selected 57 key participants which included 35 healthcare professionals from tertiary, secondary, and primary levels from Bagmati Province and 22 CVD patients (myocardial infarction and stroke) from Bagmati and Madhesh Provinces. We interviewed them using an interview guide with open-ended questions for in-depth information in a local language and in a private space. The interviews were audio-recorded, transcribed verbatim, coded, and analyzed using the thematic approach. Results. The findings indicated that the referral system for CVD cases from primary- to secondary- to tertiary-level care is inadequate and malfunctioning. The major factors affecting referral of CVD cases are centralization of CVD-specific services in few urban areas, inadequate systematic communication between the centers, self-referential, lack of human resources for CVD care, and obstacles to patient transfer due to geographical and financial reasons. Conclusion. A referral system for CVD patients is absent in the context of Nepal. Understanding and addressing key factors that affect the referral system of CVD patients may help to improve cardiac outcomes and ultimately save lives.

Patients with severe calcific native aortic valve stenosis (AS) who require valve replacement have two options, surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR). TAVR was approved in late 2011 for extremely high-risk patients and was subsequently approved for high-risk (2012), intermediate-risk (2016), and low-risk (2019) patients. In 2019, TAVR procedures surpassed SAVR procedures for the first time in the United States. The approach to anesthesia for this procedure has also evolved. Initially, general anesthesia (GA) was preferred, but currently, conscious sedation (CS) is favored. This review aims to clarify the indications and contraindications for both approaches, as well as the advantages of one approach over the other. Recent studies show that conscious sedation has better outcomes in terms of all-cause mortality, procedure complications such as stroke, myocardial infarction, infection requiring antibiotics, acute kidney injury, and the need for inotropes or vasopressors.

Objective. Primary percutaneous coronary intervention (PCI) is the best treatment for acute ST-elevation myocardial infarction (STEMI). Evidence is in favor of ticagrelor over clopidegrel in STEMI patients regarding the reduction of stent thrombosis risk during and after PCI. We compared initial thrombolysis in myocardial infarction (TIMI) flow in STEMI patients on ticagrelor vs. clopidogrel. Methods. This prospective cohort recruited 160 patients with acute STEMI, referred to the emergency department of Farshchian Heart Center, during March 2018–2019. Before angiography, the patients received clopidogrel (600 mg) or ticagrelor (180 mg) on top of aspirin. Initial TIMI flow was compared between the two groups as the primary outcome. A logistic regression was performed to calculate the predictors of initial TIMI flow. Analyses were performed using R, version 4.2.1. Results. In ticagrelor and clopidogrel groups, the mean ± standard deviation age of the patients was 59.46 ± 13.11 and 61.34 ± 11.08 years ( value = 0.33), respectively. In the ticagrelor and clopidogrel groups, initial TIMI flow grades were as follows: 0 : 50% and 71.2%, I: 26.2% and 16.2%, II: 12.5% and 10%, and III: 12.9% and 2.5%, respectively ( value = 0.005). Final TIMI flow grades were as follows: I: 26.2% and 16.2%, II: 7.5% and 13.8%, and III: 66.3% and 70%, respectively ( value = 0.41). Ticagrelor was associated with significantly higher initial TIMI flow grade compared to the clopidogrel group (adjusted odds ratio: 2.90 (95% CI: 1.51–5.72)). Conclusion. In STEMI patients who were candidates for primary PCI, ticagrelor administration led to a better initial TIMI flow grade compared to clopidogrel.