Pharmacotherapy and cardiovascular challenges: a case report of olverembatinib-induced myocardial infarction with non-obstructive coronary arteries.

The anticancer drug of tyrosine kinase-inhibitors (TKIs) has significantly improved the prognosis of patients with specific leukemia but has also increased the risk of organ adverse reactions. Herein, we present a case of a patient diagnosed with myeloproliferative neoplasms who experienced recurrent chest pain after receiving treatment with Olverembatinib. Electrocardiography and coronary angiography confirmed the diagnosis of myocardial infarction with non-obstructive coronary arteries. This case serves as a reminder for clinicians to pay more attention and actively prevent the cardiac adverse reactions of TKIs when using such medications.

Investigation of the predictive value of a novel algorithm based on coronary CT angiography regarding fractional flow reserve and revascularization in patients with stable coronary artery disease.

Fractional flow reserve (FFR) has been established as a gold standard for functional coronary ischemia. At present, the FFR can be calculated from coronary computed tomography angiography (CCTA) images (CT-FFR). Previous studies have suggested that CT-FFR outperforms CCTA and invasive coronary angiography (ICA) in determining hemodynamic significance of stenoses. Recently, a novel automatical algorithm of CT-FFR called RuiXin-FFR has been developed. The present study is designed to investigate the predictive value of this algorithm and its value in therapeutic decision making. The present study retrospectively included 166 patients with stable coronary artery disease (CAD) who underwent CCTA screening and diagnostic ICA examination at Peking University People's Hospital, in 73 of whom wire-derived FFR was also measured. CT-FFR analyses were performed with a dedicated software. All patients were followed up for at least 1 year. We validated the accuracy of RuiXin-FFR with invasive FFR as the standard of reference, and investigated the role of RuiXin-FFR in predicting treatment strategy and long-term prognosis. The mean age of the patients was 63.3 years with 63.9% male. The CT-FFR showed a moderate correlation with wire-derived FFR (r = 0.542, p < 0.0001) and diagnostic accuracy of 87.6% to predict myocardial ischemia (AUC: 0.839, 95% CI 0.728-0.950), which was significantly higher than CCTA and ICA. In the multivariate logistic regression analysis, CT-FFR ≤ 0.80 was an independent predictor of undergoing coronary revascularization (OR: 45.54, 95% CI 12.03-172.38, p < 0.0001), whereas CT-FFR > 0.80 was an independent predictor of non-obstructive CAD (OR: 14.67, 95% CI 5.42-39.72, p < 0.0001). Reserving ICA and revascularization for vessels with positive CT-FFR could have reduced the rate of ICA by 29.6%, lowered the rate of ICA in vessels without stenosis > 50% by 11.7%, and increased the rate of revascularization in patients receiving ICA by 21.2%. The average follow-up was 23.7 months, and major adverse cardiovascular events (MACE) occurred in 11 patients. The rate of MACE was significantly lower in patients with CT-FFR > 0.80. The new algorithm of CT-FFR can be used to predict the invasive FFR. The RuiXin-FFR can also provide useful information for the screening of patients in whom further ICA is indeed needed and prognosis evaluation.

DNMT1 regulates hypermethylation and silences hsa_circ_401351 in hydroquinone-induced malignant TK6 cells.

BACKGROUND: Benzene and its metabolite hydroquinone (HQ) are widely used in daily life, and long-term exposure to benzene or HQ can induce acute myeloid leukemia (AML). Circular RNAs (circRNAs) are mostly produced by reverse splicing of gene exon mRNA precursors. The modulation of circRNA expression is connected to leukemia progression; however, the molecular mechanism is still unknown. MATERIALS AND METHODS: In this study, the cells were divided into four groups: PBS control group (PBS-TK6), TK6 malignantly transformed cells induced by 10.0 µmol/L HQ (HQ-TK6), and HQ-TK6 cells treated with 5 µmol/L 5-AzaC (DNA methyltransferase inhibitor) for 24 h (HQ + 5-AzaC). HQ-TK6 cells were treated with 200 nmol/L TSA (histone deacetylation inhibitor) for 24 h (HQ + TSA). qRT-PCR was used to identify the differential hsa_circ_401351 expression between the four groups. We further determined the hsa_circ_401351 promoter methylation level with methylation-specific PCR. DNMT1 and DNMT3b were knocked down by CRISPR/Cas9 to elucidate the specific molecular mechanism of hsa_circ_401351 in HQ-TK6 cells. CCK-8 and flow cytometry detected cell proliferation and apoptosis, respectively, after hsa_circ_401351 was overexpressed in HQ-TK6 cells. RESULTS: Compared with the PBS-TK6 group, the expression of hsa_circ_401351 was found to be lower in the HQ-TK6 group. Nevertheless, treatment with 5-AzaC or TSA increased hsa_circ_401351 expression, with the upregulation being more pronounced in the TSA group. The expression of hsa_circ_401351 in the DNMT1 knockdown group was dramatically increased by 50% compared to that in the control group, and the DNA methylation level of the hsa_circ_401351 promoter region was decreased. When hsa_circ_401351 was overexpressed, HQ-TK6 cell proliferation was significantly slowed after 48 h compared with the control group. Flow cytometry showed that cells were mainly arrested in G1 phase, and apoptosis was significantly enhanced. Similarly, qRT-PCR and Western blot data showed significant reductions in Caspase-3 mRNA and protein production, and Bcl-2 mRNA levels were also elevated. CONCLUSIONS: Overall, our research showed that elevated DNMT1 expression in HQ-TK6 cells increased methylation levels and decreased expression of the hsa_circ_401351 promoter region, limiting its ability to suppress HQ-TK6 cell growth and enhance apoptosis.

Abnormal inter-ventricular diastolic mechanical delay in patients with ST-segment elevation myocardial infarction.

BACKGROUND: This study aimed to investigate the ventricular mechanical relaxation pattern and its clinical influence in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: Echocardiography was performed to measure mitral and tricuspid diastolic opening times. Left ventricular diastolic mechanical delay (LVMDd) was defined as diastolic filling of the right ventricle earlier than that of the left ventricle, and right ventricular diastolic mechanical delay (RVMDd) was defined as the right ventricular diastolic filling later than left ventricular filling. RESULTS: Among 152 patients with STEMI, 100 (65.8%) had LVMDd, and 47 (30.9%) had RVMDd. In-hospital complications were significantly increased in patients with RVMDd (61.6% vs. 41.0%, P = 0.017). Those with RVMDd exhibited significantly lower left ventricular global longitudinal strain (11.7 ± 4.1% vs. 13.2 ± 4.0%, P = 0.035), global work index (913.8 ± 365.9 vs. 1098.9 ± 358.8 mmHg%, P = 0.005) and global constructive work (1218.6 ± 392.8 vs. 1393.7 ± 432.7 mmHg%, P = 0.021). Mitral deceleration time significantly decreased (127.4 ± 33.5 vs. 145.6 ± 41.7 ms, P = 0.012), and the ratio of early mitral inflow to early mitral annular velocity (E/E') significantly increased [13.0(11.0-20.0) vs. 11.9(9.3-14.3), P = 0.006] in the RVMDd group. Logistic regression analysis showed that age (odds ratio [OR]:0.920; P = 0.001), brain natriuretic peptide level (OR: 1.1002; P = 0.036) and mitral E/E' (OR: 1.187; P = 0.003) were independently associated with RVMDd. CONCLUSIONS: Delayed right ventricular filling is related to more severe left ventricular systolic and diastolic dysfunction in STEMI patients. More attention should be paid to patients with RVMDd to prevent adverse events during hospitalization.

Hydroxychloroquine induces apoptosis of myeloid-derived suppressor cells via up-regulation of CD81 contributing to alleviate lupus symptoms.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that results from widespread immune complex deposition and secondary tissue injury. Hydroxychloroquine (HCQ) has been used clinically to treat SLE, while its exact mechanism has still remained elusive. Some studies have shown that myeloid-derived suppressor cells (MDSCs) play a vital role in the regulation of SLE. In this study, we aimed to explore the effects of HCQ on the apoptosis of MDSCs in lupus mice and its possible molecular regulatory mechanism. METHODS: We constructed the imiquimod (IMQ)-induced lupus model in mice. The proportion and apoptosis of MDSCs were measured by flow cytometry. CD81-overexpressed adeno-associated virus was intraperitoneally injected into the lupus mice. We also transfected the CD81 siRNA into bone marrow-derived MDSCs, and employed qRT-PCR and Western blotting to quantify the level of CD81. RESULTS: The results showed that HCQ ameliorated IMQ-induced lupus symptoms, and simultaneously inhibited the expansion of MDSCs. In particular, HCQ induced the apoptosis of MDSCs, and also up-regulated the expression level of CD81 in MDSCs, which might indicate the relationship between the expression level of CD81 and the apoptosis of MDSCs. CD81 was further confirmed to participate in the apoptosis of MDSCs and lupus disease progression by overexpressing CD81 in vivo. Molecular docking experiment further proved the targeting effect of HCQ on CD81. And then we interfered CD81 in bone marrow derived MDSCs in vitro, and it was revealed that HCQ rescued the decreased expression level of CD81 and relieved the immune imbalance of Th17/Treg cells. CONCLUSION: In summary, HCQ promoted the apoptosis of MDSCs by up-regulating the expression level of CD81 in MDSCs, and ultimately alleviated lupus symptoms. Our results may assist scholars to develop further effective therapies for SLE.

The Coronary Angiography-Derived Index of Microcirculatory Resistance Predicts Left Ventricular Performance Recovery in Patients with ST-Segment Elevation Myocardial Infarction.

Objectives: The present study is designed to investigate the impact of coronary angiography-derived index of microcirculatory resistance (caIMR) on left ventricular performance recovery. Background: IMR has been established as a gold standard for coronary microvascular assessment and a predictor of left ventricular recovery after ST-segment elevation myocardial infarction (STEMI). CaIMR is a novel and accurate alternative of IMR. Methods: The present study retrospectively included 80 patients with STEMI who underwent primary percutaneous coronary intervention (PCI). We offline performed the post-PCI caIMR analysis of the culprit vessel. Echocardiography was performed within the first 24 hours and at 3 months after the index procedure. Left ventricular recovery was defined as the change in left ventricular ejection fraction (LVEF) more than zero. Results: The mean age of the patients was 58.0 years with 80.0% male. The average post-PCI caIMR was 43.2. Overall left ventricular recovery was seen in 41 patients. Post-PCI caIMR (OR: 0.948, 95% CI: 0.916-0.981, p = 0.002), left anterior descending as the culprit vessel (OR: 3.605, 95% CI: 1.23-10.567, p = 0.019), and male (OR: 0.254, 95% CI: 0.066-0.979, p = 0.047) were independent predictors of left ventricular recovery at 3 months follow-up. A predictive model was established with the best cutoff value for the prediction of left ventricular recovery 2.33 (sensitivity 0.610, specificity 0.897, and area under the curve 0.765). In patients with a predictive model score less than 2.33, the LVEF increased significantly at 3 months. Conclusions: The post-PCI caIMR can accurately predict left ventricular functional recovery at 3 months follow-up in patients with STEMI treated by primary PCI, supporting its use in clinical practice.

Usefulness of echocardiographic myocardial work in evaluating the microvascular perfusion in STEMI patients after revascularization.

BACKGROUND: Left ventricular myocardial work (MW) assessed by echocardiography has recently been introduced as a new index of global and regional myocardial performance. The presence of microvascular obstruction after revascularization in ST-segment elevation myocardial infarction (STEMI) patients predicts poor clinical outcomes. This study aimed to explore the usefulness of MW in identifying impaired microvascular perfusion (MVP) in the patients with STEMI after revascularization. METHODS: One hundred and sixty STEMI patients who underwent myocardial contrast echocardiography (MCE) within 48 h after percutaneous coronary intervention (PCI) were included. Patients were divided into normal MVP and impaired MVP groups according to the myocardial perfusion score. The clinical data, coronary angiography results and echocardiographic data including Global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were collected. RESULTS: Impaired MVP was found in 60% of patients. Compared with the normal MVP group, GWI (909.2 ± 287.6 mmHg% vs. 1191.2 ± 378.2 mmHg%), GCW (1198.3 ± 339.6 mmHg% vs. 1525.9 ± 420.5 mmHg%), GWE (82.7 ± 7.8% vs. 86.8 ± 5.6%) and GLS (- 11.0 ± 3.4% vs. - 14.4 ± 3.8%) were significantly reduced in the impaired MVP group. Whereas there was no statistically significant difference in left ventricular ejection fraction (LVEF) and GWW, multivariate logistic regression analysis showed that peak troponin I (OR 1.017, 95% CI 1.006-1.029; P = 0.004), final TIMI flow ≤ 2 (OR 16.366, 95% CI 1.998-134.06; P = 0.009), left ventricular end-diastolic volume index (LVEDVi) (OR 1.139 95% CI 1.048-1.239; P = 0.002), and GWI (OR 0.997 95% CI 0.994-1.000; P = 0.029) were independently associated with impaired MVP. GWI showed a good sensitivity (86.8%) but low specificity (53.7%) in identifying impaired MVP (AUC 0.712, 95% CI 0.620-0.804; P < 0.001). Combination with GWI can improve the diagnostic value of TNI or LVEVi for impaired MVP. CONCLUSION: Impaired MVP is relatively common in STEMI patients after revascularization and independently associated with left ventricular GWI assessed by echocardiography. GWI confer incremental value to MVP assessment in STEMI patients.

Coronary microcirculation dysfunction evaluated by myocardial contrast echocardiography predicts poor prognosis in patients with ST-segment elevation myocardial infarction after percutaneous coronary intervention.

BACKGROUND: The mortality rate of acute ST-segment elevation myocardial infarction (STEMI) remains substantial, despite advances in treatment strategies. Coronary microcirculation dysfunction (CMD) persists after percutaneous coronary intervention (PCI) in a substantial proportion of STEMI patients. The association between CMD assessed using myocardial contrast echocardiography (MCE) and prognosis requires further elucidation. This study aimed to evaluate the impact of CMD after successful PCI on the prognosis of patients with STEMI. METHODS: We enrolled 167 patients with STEMI after PCI who underwent MCE during hospitalization between January 2018 and March 2022. Patients were classified into the CMD and non-CMD groups according to the results of MCE. The clinical data and MCE results of both groups were analyzed. Follow-up was conducted for major adverse cardiac events. RESULTS: MCE detected CMD in 105 patients (62.9%). The CMD group contained fewer hypertensive patients (55.2% versus 74.2%, P = 0.015). Patients with CMD exhibited significantly higher levels of plasma troponin I (TnI) [73.2 (23.0-124.0) versus 28.9 (12.7-80.2) ng/mL, P = 0.004], higher levels of plasma B-type natriuretic peptide [255 (99-641) versus 193 (59-389) pg/mL, P = 0.004], poorer Killip classification (P = 0.038), and different culprit vessels (P < 0.001) compared to the non-CMD group. Patients with CMD exhibited lower left ventricular ejection fraction [50 (43-58) versus 61 (54-67) %, P < 0.001], poorer wall motion score index values (1.68 ± 0.4 versus 1.31 ± 0.26, P < 0.001) and poorer left ventricular global longitudinal strain [-11.2 (-8.7 to -14.1) versus -13.9 (-11.0 to -17.2) %, P < 0.001] compared to the non-CMD group. Patients underwent follow-up for 13 (7-20) months. After adjusting for hypertension, peak TnI level, culprit vessel, and Killip classification, CMD was an independent predictor of total major adverse cardiac events at 13 months' follow-up [adjusted odds ratio (OR), 2.457; 95% confidence interval (CI), 1.042-5.790; P = 0.040], and patients with CMD had a higher risk of hospitalization for heart failure (adjusted OR, 5.184; 95% CI, 1.044-25.747; P = 0.044) and repeat myocardial infarction (adjusted OR, 2.896; 95% CI, 1.109-7.565; P = 0.030). CONCLUSIONS: MCE is a safe and effective method for detecting CMD in patients with STEMI. CMD detected by MCE after successful PCI in patients with STEMI is a common occurrence, which is associated with a significantly worse prognosis, especially hospitalization for heart failure and repeat myocardial infarction.

Left ventricular function and coronary microcirculation in patients with mild reduced ejection fraction after STEMI.

BACKGROUND: The characteristics of heart failure (HF) with mildly reduced ejection fraction (EF) (HFmrEF) overlap with those of HF with reduced EF (HFrEF) and HF with preserved EF (HFpEF) and need to be further explored. This study aimed to evaluate left ventricular (LV) function and coronary microcirculation in patients with mildly reduced ejection fraction after acute ST-segment elevation myocardial infarction (STEMI). METHODS: We enrolled 119 patients with STEMI who had undergone speckle tracking imaging and myocardial contrast echocardiography during hospitalization from June 2016 to June 2021. They were classified into normal, HFmrEF, and HFrEF groups according to their left ventricular EF (LVEF): ≥ 50%, 40-50%, and ≤ 40%, respectively. The data of the HFmrEF group were analyzed and compared with those of the normal and HFrEF groups. RESULTS: HFmrEF was observed in 32 patients (26.9%), HFrEF in 17 (14.3%), and normal LVEF in 70 patients (58.8%). The mean global longitudinal strain (GLS) of all patients was - 11.9 ± 3.8%. The GLS of HFmrEF patients was not significantly different from that of the HFrEF group (- 9.9 ± 2.5% and - 8.0 ± 2.3%, respectively, P = 0.052), but they were both lower than that of the normal group (- 13.8% ± 3.5%, P < 0.001). The HFmrEF group exhibited significantly poorer myocardial perfusion index (1.24 ± 0.33) than the normal group (1.08 ± 0.14, P = 0.005) but displayed no significant difference from the HFrEF group (1.18 ± 0.19, P = 0.486). Moreover, a significant difference in the incidence of regional wall motion (WM) abnormalities in the three groups was observed (P = 0.009), and the WM score index of patients with HFmrEF was 1.76 ± 0.30, similar to that of patients with HFrEF (1.81 ± 0.43, P = 0.618), but poorer than that in the normal group (1.33 ± 0.25, P < 0.001). CONCLUSIONS: GLS is a more sensitive tool than LVEF for detecting LV systolic dysfunction. The LV systolic function, coronary microcirculation, and WM in patients with HFmrEF was poorer than that of patients with normal LVEF, but comparable to that in patients with HFrEF. Patients with HFmrEF after STEMI require more attention and appropriate management.

White thrombi on optical coherence tomography after rotational atherectomy of severely calcified coronary lesions.

PURPOSE: Rotational atherectomy (RA) has improved percutaneous treatment of severely calcified coronary lesions, but the "no-reflow" phenomenon remains a serious complication. Platelet activation by RA may contribute to no-reflow, and the use of optical coherence tomography (OCT) to test the effect of RA on white thrombus could confirm platelet activation indirectly. METHODS: We analyzed 53 consecutive patients with severely calcified lesions on coronary angiography. All patients were examined with OCT. In total, 20 patients who received RA and for whom OCT imaging was performed before and after RA and stent implantation comprised the RA group. The remaining 33 patients formed the control group, for whom OCT imaging was performed before balloon dilatation and after stent implantation. RESULTS: The patients in the RA group were older and had a higher incidence of diabetes mellitus. In the control group, there was no thrombogenesis during the procedure, whereas in the RA group, all the target vessels had white thrombi on OCT after RA. The average number of white thrombi per lesion after RA was 7.23 ± 4.4, and the average length of white thrombus was 0.51 ± 0.33 mm. Statistical analysis with Pearson's correlation coefficient showed that thrombus load was related to burr size (r = 0.575, p = 0.040) and number of rotations (r = 0.599, p = 0.031). CONCLUSION: White thrombi during RA can be verified by performing OCT. Treating calcified lesions with RA may enhance thrombogenesis. These data suggest using appropriate therapy to avoid no-reflow during RA.