Proteomic and Phosphoproteomic Analysis of Right Ventricular Hypertrophy in the Pulmonary Hypertension Rat Model.

Pulmonary arterial hypertension (PAH) is a progressive disease that affects both the lungs and heart. Right ventricle (RV) hypertrophy is a primary pathological feature of PAH; however, its underlying molecular mechanisms remain insufficiently studied. In this study, we employed tandem mass tag (TMT)-based quantitative proteomics for the integrative analysis of the proteome and phosphoproteome of the RV derived from monocrotaline-induced PAH model rats. Compared with control samples, 564 significantly upregulated proteins, 616 downregulated proteins, 622 downregulated phosphopeptides, and 683 upregulated phosphopeptides were identified (P < 0.05, abs (log2 (fold change)) > log2 1.2) in the MCT samples. The quantitative real-time polymerase chain reaction (qRT-PCR) validated the expression levels of top 20 significantly altered proteins, including Nppa (natriuretic peptides A), latent TGF-ß binding protein 2 (Ltbp2), periostin, connective tissue growth factor 2 (Ccn2), Ncam1 (neural cell adhesion molecule), quinone reductase 2 (Nqo2), and tropomodulin 4 (Tmod4). Western blotting confirmed the upregulation of Ncam1 and downregulation of Nqo2 and Tmod4 in both MCT-induced and hypoxia-induced PH rat models. Pathway enrichment analyses indicated that the altered proteins are associated with pathways, such as vesicle-mediated transport, actin cytoskeleton organization, TCA cycle, and respiratory electron transport. These significantly changed phosphoproteins were enriched in pathways such as diabetic cardiomyopathy, hypertrophic cardiomyopathy, glycolysis/gluconeogenesis, and cardiac muscle contraction. In summary, this study provides an initial analysis of the RV proteome and phosphoproteome in the progression of PAH, highlighting several RV dysfunction-associated proteins and pathways.

Survival outcomes correlate with the level of cell-free circulating DNA in ST-elevation myocardial infarction.

Background: Myocardial infarction (MI) can lead to higher cellular damage, making cell-free DNA (cfDNA) a potential biomarker for assessing disease severity. The aim of this study is to evaluate survival predictions using cfDNA measurements and assess its correlation with MI. Materials and Methods: A direct fluorescence assay was employed to measure cfDNA content in the blood samples of participants. The inclusion criteria included patients who gave informed consent, suffering from ST-elevation myocardial infraction (STEMI) based on established diagnostic criteria (joint ESC/ACC guidelines), between the age of 18 and 80 years old, and had elevated troponin biomarker levels. The study included 150 patients diagnosed with STEMI and 50 healthy volunteers as controls. Serial monitoring of patients was conducted to track their postdisease status. The rate of change of cfDNA was calculated and daily measurements for 7 days were recorded. Results: Mean levels of cfDNA were found to be 5.93 times higher in patients with STEMI compared to healthy controls, providing clear evidence of a clinical correlation between cfDNA and STEMI. Patients were further categorized based on their survival status within a 90-day period. The study observed a strong predictive relationship between the rate of change of cfDNA during daily measurements and survival outcomes. To assess its predictive capability, a receiver operating characteristics (ROC) curve analysis was performed. The ROC analysis identified an optimal cutoff value of 2.50 for cfDNA, with a sensitivity of 81.5% and specificity of 74.0% in predicting disease outcomes. Conclusion: This study demonstrates a robust association between cfDNA and STEMI, indicating that cfDNA levels can be a valuable early prognostic factor for patients. Serial measurements of cfDNA during early disease onset hold promise as an effective approach for predicting survival outcomes in MI patients.

Transcriptomic profiling highlights cell proliferation in the progression of experimental pulmonary hypertension in rats.

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by pulmonary vascular remolding and occlusion, leading to the elevated pulmonary arterial pressures, right ventricular hypertrophy, and eventual heart failure if left untreated. Understanding the molecular mechanisms underlying the development and progression of pulmonary hypertension (PH) is crucial for devising efficient therapeutic approaches for the disease. Lung homogenates were collected weekly and underwent RNA-sequencing in the monocrotaline (MCT)-induced PH rat model to explore genes associated with PH progression. Statistical analyses revealed 1038, 1244, and 3125 significantly altered genes (P < 0.05, abs (log2fold change) > log21.5) between control and MCT-exposed rats during the first, second, and third week, respectively. Pathway enrichment analyses revealed involvement of cell cycle and innate immune system for the upregulated genes, GPCR and VEGF signaling for the downregulated genes. Furthermore, qRT-PCR validated upregulation of representative genes associated with cell cycle including Cdc25c (cell division cycle 25C), Cdc45, Top2a (topoisomerase IIα), Ccna2 (cyclin A2) and Ccnb1 (cyclin B1). Western blot and immunofluorescence analysis confirmed increases in PCNA, Ccna2, Top2a, along with other proliferation markers in the lung tissue of MCT-treated rats. In summary, RNA sequencing data highlights the significance of cell proliferation in progression of rodent PH.

Case Report: Integrated echocardiographic assessment guided Liwen procedure for treating obstructive hypertrophic cardiomyopathy with ventricular aneurysm.

Hypertrophic cardiomyopathy (HCM) is a genetic myocardial disease, with an estimated incidence of 0.2%-6%, and is the main cause of sudden cardiac death (SCD) in young athletes. Left ventricular apical aneurysm (LVAA) is a rare subtype of HCM, accounting for about 5% of HCM patients, and has a higher incidence of cardiovascular adverse events. In cases of hypertrophic obstructive cardiomyopathy with LVAA (HOCM-LVAA) that do not respond adequately to optimized medical therapy, the echocardiography-guided percutaneous intra-myocardial septal radiofrequency ablation (PIMSRA, Liwen procedure) emerges as a promising and effective novel therapeutic approach. In this case report, we present for the first time a comprehensive application of echocardiographic techniques, including TTE, 2-D STE, and contrast enhancement, in the diagnosis, treatment, surgical guidance, and assessment of therapeutic outcomes in a case of HOCM-LVAA.

The prognostic value of left atrial and left ventricular strain in patients after ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention.

BACKGROUND: Global longitudinal strain (GLS) based on two-dimensional speckle-tracking echocardiography (2D-STE) might better reflect left ventricular (LV) contractile performance than conventional parameters. Recently, left atrial (LA) strain has been used as a more accurate alternative to assessing LA performance. The aim in this study was to assess the clinical prognostic value of left ventricular GLS (LV GLS) and peak atrial longitudinal strain (PALS) in patients after ST-segment elevation myocardial infarction (STEMI). METHODS: The study enrolled 199 patients who underwent primary percutaneous coronary intervention (pPCI) for first STEMI. Conventional and 2D-STE were performed within 48 h after pPCI. LV GLS and PALS were related to LV remodeling at 6-month follow-up and to adverse events. RESULTS: Diabetes mellitus, GLS and PALS independently predicted LV remodeling. With multivariable Cox proportional hazards, diabetes mellitus, GLS and PALS were predictive of adverse clinical outcomes. However, PALS did not add significant incremental value beyond LV GLS in the prediction of LV remodeling (increase in area under the receiver-operator characteristic curve [AUC]: 0.05, p = 0.24) and clinical events (even a decrease in AUC: 0.03, p = 0.69). CONCLUSIONS: Both GLS and PALS provide independent prognostic value for adverse LV remodeling and clinical outcomes after STEMI. However, the ability of the combination of PALS and GLS to predict LV remodeling and clinical outcomes may not be superior to that of a single indicator.

Evaluation of right ventricular performance and impact of continuous positive airway pressure therapy in patients with obstructive sleep apnea living at high altitude.

Obstructive sleep apnea syndrome (OSAS) can lead to alterations in right ventricular (RV) performance and pulmonary vascular haemodynamics. Additionally, altitude-related hypoxia is associated with pulmonary vasoconstriction, and the effect of high-altitude on the pulmonary circulation in OSAS patients can be further altered. We sought to assess alterations in RV morphology and function in OSAS patients living at high altitude by way of 2-dimensional speckle tracking echocardiography (2D-STE), real-time 3- dimensional echocardiography (RT-3DE) and cardiac biomarkers. We also evaluate the impact of continuous positive airway pressure (CPAP) treatment on RV performance. Seventy-one patients with newly diagnosed OSAS and thirty-one controls were included in this study. All individuals were assessed for cardiac biomarkers as well as underwent 2D-STE and RT-3DE. Forty-five OSAS patients underwent CPAP therapy for at least 24 weeks and were studied before and after CPAP treatment. RT-3DE was used to measure RV volume, and calculate RV 3D ejection fraction (3D RVEF). Peak systolic strain was determined. Cardiac biomarkers, including C-reactive protein (CRP), N-terminal pro-B-type natriuretic peptide, and cardiac troponin T were also measured. Right atrium volume index, RV volume, RV volume index, systolic pulmonary artery pressure (sPAP), pulmonary vascular resistance (PVR) and level of serum CRP were significantly higher in OSAS group, while OSAS patients showed lower 3D RVEF and RV longitudinal strains. Compared to the patients with sPAP < 40 mmHg, RV longitudinal strains in patients with sPAP ≥ 40 mmHg were lower. Both RV global longitudinal strain and sPAP were associated with apnea-hypopnea index. Patients treated with 6 months of CPAP therapy had significant improvement in RV geometry and performance. RV structural abnormalities and RV function impairments were observed in OSAS patients living at moderate high altitude compared to control highlanders. The reversibility of these changes after application of CPAP were further confirmed.

Effect of coronary collateral circulation on the prognosis of elderly patients with acute ST-segment elevation myocardial infarction treated with underwent primary percutaneous coronary intervention.

Investigate the effect of coronary collateral circulation (CCC) on the prognosis of elderly patients with acute ST-segment elevation myocardial infarction (STEMI) and acute total occlusion (ATO) of a single epicardial coronary artery.Three hundred forty-six advanced-age patients (age ≥60 years) with STEMI and ATO who underwent primary percutaneous coronary intervention (PCI) were enrolled in this study. According to the Rentrop grades, the patients were assigned to the poor CCC group (Rentrop grade 0-1) and good CCC group (Rentrop grade 2-3).Multivariate logistic regression analysis revealed that poor coronary collateral circulation was an independent factor for Killip class ≥2 (odds ratio [OR]: -1.559; 95% confidence interval [CI]: 1.346-2.378; P = .013), the use of an intra-aortic balloon pump (IABP) (OR: -1.302; 95% CI: 0.092-0.805; P = .019), and myocardial blush grade (MBG) 3 (OR: 1.516; 95% CI: 2.148-9.655; P < .001). We completed a 12-month follow-up, during which 52 patients (15.0%) were lost to follow-up and 19 patients (5.5%) died. Univariate analysis (Kaplan-Meier and log-rank tests) suggested that poor CCC had a significant effect on all-cause mortality (P = .046), while multivariate analysis (Cox regression analysis) indicated that CCC had no statistically significant effect on all-cause mortality (P = .089) after the exclusion of other confounding factors. After excluding the influence of other confounding factors, this study showed that the mortality rate increased by 26.9% within 1 year for every 1-hour increment of time of onset. The mortality rate in patients with Killip class ≥2 was 8.287 times higher than that in patients with Killip class 0 to 1. The mortality rate in patients over 75 years was 8.25 times higher than that in patients aged 60 to 75 years. The mortality rate in patients with myocardial blush grade 3 (MBG 3) was 5.7% higher than that in patients with MBG 0-2.The conditions of CCC in the acute phase had no significant direct effect on all-cause mortality in patients, but those with good CCC had a higher rate of MBG 3 after primary PCI and a lower rate of Killip ≥2.