A case of repeated in-stent restenosis of coronary artery as a primary manifestation of seronegative antiphospholipid antibody syndrome.

BACKGROUND: Antiphospholipid antibody syndrome (APS) is a multisystemic autoimmune disorder which affects many organs or systems; however, coronary artery is relatively less frequently involved. CASE PRESENTATION: A 65-year-old female with effort chest pain was hospitalized for unstable angina in Janurary, 2015. Coronary angiography revealed sub-total occlusion of proximal left anterior descending (LAD) coronary artery, where a drug-eluting stent was successfully deployed. The patient experienced multiple in-stent stenosis at LAD coronary artery and coronary artery bypass graft (CABG) surgery was advised. Subsequently, severe stenosis of left circumflex (LCX) coronary artery emerged, and the patient suffered persistent in-stent restenosis. Eventually, the patient was diagnosed with seronegative antiphospholipid antibody syndrome and salvaged by immunosuppressants. CONCLUSIONS: Repeated in-stent restenosis could be a primary manifestation of seronegative antiphospholipid antibody syndrome, and suppression of autoimmune activity and inflammation other than purely coronary revascularization might be a better option.

Gut Microbiota-Derived Tryptophan Metabolite Indole-3-aldehyde Ameliorates Aortic Dissection.

Tryptophan, an essential dietary amino acid, is metabolized into various metabolites within both gut microbiota and tissue cells. These metabolites have demonstrated potential associations with panvascular diseases. However, the specific relationship between tryptophan metabolism, particularly Indole-3-aldehyde (3-IAId), and the occurrence of aortic dissection (AD) remains unclear. 3-IAId showed an inverse association with advanced atherosclerosis, a risk factor for AD. In this study, we employed a well-established ß-aminopropionitrile monofumarate (BAPN)-induced AD murine model to investigate the impact of 3-IAId treatment on the progression of AD. Our results reveal compelling evidence that the administration of 3-IAId significantly mitigated aortic dissection and rupture rates (BAPN + 3-IAId vs. BAPN, 45% vs. 90%) and led to a notable reduction in mortality rates (BAPN + 3-IAId vs. BAPN, 20% vs. 55%). Furthermore, our study elucidates that 3-IAId exerts its beneficial effects by inhibiting the phenotype transition of vascular smooth muscle cells (VSMCs) from a contractile to a synthetic state. It also mitigates extracellular matrix degradation, attenuates macrophage infiltration, and suppresses the expression of inflammatory cytokines, collectively contributing to the attenuation of AD development. Our findings underscore the potential of 3-IAId as a promising intervention strategy for the prevention of thoracic aortic dissection, thus providing valuable insights into the realm of vascular disease management.

Prognostic value and clinical usefulness of PIANO score in patients undergoing primary percutaneous coronary intervention.

BACKGROUND: In our previous study, the PIANO score was constructed to predict the occurrence of no-reflow phenomenon in patients undergoing primary percutaneous coronary intervention (PCI). In the current analysis, we sought to evaluate the prognostic value and clinical usefulness of the PIANO score in this population. METHODS: Patients with acute myocardial infarction (AMI) undergoing primary PCI were consecutively enrolled and followed up in this register. The endpoint of interest was all-cause mortality at 2 years after the procedure. The clinical benefits of thrombus aspiration (TA) during primary PCI in certain subgroups were also evaluated as exploratory analyses. RESULTS: A total of 2100 patients were identified, and 54.3% had high (≥8) PIANO score. After 2-year follow-up, patients with high PIANO score had higher risk of all-cause mortality after adjustment for propensity score (6.7% vs. 3.1%, adjusted hazard ratio = 2.11 [1.21-3.68], p = 0.008), especially in the first month (adjusted hazard ratio = 2.33 [1.17-4.65], p = 0.017). Restricted cubic spline analysis indicated the linear association between the PIANO score and 2-year all-cause mortality (nonlinear p = 0.556). Further analysis demonstrated that TA did not reduce all-cause mortality in the overall patients, as well as in those with visible thrombus, high thrombus burden, or occlusive lesions. However, the PIANO score defined "high-risk" (PIANO score ≥ 8) patients could benefit from it. CONCLUSIONS: The PIANO score had potential prognostic value in patients with AMI undergoing primary PCI. It might also be helpful for identifying patients who would benefit from TA. These observations require further confirmation in future studies.

Device-based antegrade dissection re-entry versus parallel wire techniques for the percutaneous revascularization of coronary chronic total occlusions.

BACKGROUND: Device-based antegrade dissection re-entry (ADR) and parallel wire technique (PWT) are two important techniques in the antegrade approach in percutaneous coronary intervention (PCI) of chronic total occlusion (CTO). The study is aimed to compare the procedural and mid-term outcomes between device-based ADR using the CrossBoss/Stingray system and PWT in CTO PCI. METHODS: Data was retrospectively collected from consecutive patients who underwent CTO PCI using device-based ADR or PWT. CTO due to in-stent restenosis were excluded. RESULTS: A total of 273 patients were included in the study (n = 55 in device-based ADR group, n = 218 in PWT group). Baseline characteristics were similar across groups except for higher prevalence of prior PCI and lower level of lipid profile in the ADR group. Moreover, although patients in the ADR group showed higher contrast volume (441.6 ± 162.4 mL vs. 361.5 ± 142.1 mL, p < 0.001), more intravascular ultrasound guidance (50.9% vs. 22.9%, p < 0.001), more guidewires used (4.6 ± 1.4 vs. 3.4 ± 1.2, p < 0.001) and higher troponin T level after PCI (0.167 vs. 0.087, p = 0.004), the technical success, procedural success and in-hospital complications were similar between the two groups. During a median follow-up of 1 year, the ADR group showed no difference in major adverse cardiac events (MACE, including all cause death, nonfatal myocardial infarction, and ischemia driven target vessel revascularization) (7.3% vs. 14.7%, p = 0.150) as compared with the PWT group. CONCLUSIONS: In the documented center, the use of device-based ADR for CTO PCI showed no difference in in-hospital complications and mid-term MACE as compared with PWT, despite higher procedure complexity in ADR group.

Alpha-lipoic acid protects against aortic aneurysm and dissection by improving vascular smooth muscle cell function.

Alpha-Lipoic acid (ALA) plays a protective role in a variety of vascular diseases, however, its effect on aortic aneurysm and dissection (AAD) has not been reported. In this study, we found that Alpha-Lipoic Acid treatment significantly improved the AAD and AAA development, which was demonstrated by ameliorated aneurysmal dilation, decreased aortic dissection and aneurysm incidence, improved aortic morphology and inhibited elastin degradation. ALA blunted extra-cellular matrix degradation, vascular smooth muscle cell (VSMC) loss and phenotype transformation. Moreover, the protective effect of ALA on VSMCs may be related to the amelioration of mitochondrial dysfunction. In conclusion, our study revealed that ALA exerts inhibitory effects against progression of AAD, thus suggesting that ALA may be a novel therapeutic molecule for AAD.

Impact of Subintimal Plaque Modification on Reattempted Chronic Total Occlusions Percutaneous Coronary Intervention.

BACKGROUND: Predictors of success in reattempted chronic total occlusion (CTO) percutaneous coronary intervention (PCI) procedures remain obscure, mainly owing to the lack of consecutive angiograms and procedural records of initial attempts in the same cohort. OBJECTIVES: This study sought to investigate the factors predicting the success of reattempted CTO PCI procedures. METHODS: A total of 208 consecutive patients who underwent a failed CTO PCI attempt and received reattempted procedure at the same cardiac center were retrospectively analyzed. Predictors of the success of reattempted procedures were evaluated. RESULTS: The overall technical success rate of reattempted CTO PCI procedures was 71.2%. Subintimal plaque modification (SPM) was implemented in 35 (16.8%) procedures in initial attempts. The reattempted technical success rate was 93.3% in cases in which SPM with guidewire (GW) crossing was achieved in the initial attempt; however, the success rate was 55.0% for procedures involving SPM without GW crossing. SPM with GW crossing (OR: 11.21; 95% CI: 1.31-96.16; P = 0.028), referral to high-volume operators (OR: 2.38; 95% CI: 1.14-4.98; P = 0.021), and a bidirectional approach (OR: 2.31; 95% CI: 1.12-4.79; P = 0.024) were positive independent predictors of technical success in the subsequent reattempt. The time interval for reattempt (per 90-day increment) was negatively correlated with the technical success of the reattempted procedures (OR: 0.85; 95% CI: 0.73-0.98; P = 0.030). CONCLUSIONS: This study identified independent predictors of success in reattempted CTO PCI procedures. SPM with GW crossing achieved in the initial attempt is associated with a higher success rate in the subsequent reattempt.

Functional comparison of different jailed balloon techniques in treating non-left main coronary bifurcation lesions.

BACKGROUND: There is a paucity of data comparing functional difference between active jailed balloon technique (A-JBT) and conventional jailed balloon technique (C-JBT) in treating non-left main coronary bifurcation lesions (CBLs). METHODS: In this retrospective cohort study, we consecutively enrolled 232 patients with non-left main CBLs who underwent percutaneous coronary intervention (PCI) using JBTs between January 2018 and March 2019. Among them, 191 patients entered the final analysis with 12-months angiographic follow-up. We stratified patients into A-JBT group (130 patients) and C-JBT group (61 patients). The functional analysis by Murray law-based quantitative flow ratio (µQFR) and Seattleanginaquestionnaire (SAQ) were performed to compare the two techniques. RESULTS: Compared with C-JBT group, A-JBT group observed a lower abrupt (0.8% vs. 11.1%, p = 0.002) and final SB occlusion (0 vs. 7.9%, p = 0.005). Meanwhile, A-JBT group had a significantly higher µQFR of side branch (SB) both post-PCI and 12-months follow-up (median [interquartile range (IQR)]: 0.91 (0.86-0.96) vs. 0.82 (0.69-0.92), p < 0.001; median [IQR]: 0.95 (0.89-0.98) vs. 0.85 (0.74-0.93), p < 0.001) than C-JBT group. Besides, A-JBT group gained a µQFR improvement at follow-up period compared with post-PCI data (median [IQR]: 0.95 [0.89-0.98] vs. 0.91[0.86-0.96] of SB, p < 0.001) and a higher SAQ scores at 12-months follow-up compared with C-JBT group (p < 0.001). CONCLUSIONS: Compared with C-JBT, A-JBT provided excellent SB protection during MV stenting and improved the SB functional blood flow as well as the angina relief even after 12 months.

The gut microbiome and microbial metabolites in acute myocardial infarction.

Emerging evidence has highlighted the role of gut microbiome in human health. However, the integrative role of gut microbiome and microbial metabolites in acute myocardial infarction (AMI) remains unclear. The current study profiles the microbial community through 16S rRNA gene sequencing and shotgun metagenomic sequencing and measures fecal short-chain fatty acids and circulating choline pathway metabolites among 117 new-onset AMI cases and 78 controls. Significant microbial alternations are observed in AMI patients compared with controls (P = 0.001). The abundances of nine species (e.g., Streptococcus salivarius and Klebsiella pneumoniae) are positively associated, and one species (Roseburia hominis) is inversely associated with AMI status and severity. A gut microbial score at disease onset is associated with the risk of major adverse cardiovascular events in 3.2 years (hazard ratio [95% CI]: 2.01 [1.04-4.24]) in AMI patients. The molar proportions of fecal acetate and butyrate are higher, and the circulating levels of choline and carnitine are lower in AMI patients than in controls. In addition, disease classifiers show that AMI cases and controls have a more distinct pattern in taxonomical composition than in pathways or metabolites. Our findings suggest that microbial composition and functional potentials are associated with AMI status and severity.

Characteristics, Management, and Prognosis of Spontaneous Coronary Intramural Hematoma.

Spontaneous coronary intramural hematoma (SCIH) was one type of spontaneous coronary artery dissection without obvious intimal tear, which is easy to misdiagnose. We aimed to study the characteristics, management, and prognosis of SCIH in our center. All the SCIH patients (n = 30) diagnosed by coronary angiography from January 1, 2012 to December 31, 2018 were enrolled. The demographic characteristics, history, therapy, and follow-up were collected. The mean age of the patients was 51.8 ± 9.5 years. Most of the patients were females (66.7%) with hypertension. Patients with diffuse lesion, focal lesion, and multiple vessels were 70%, 13.3%, and 16.7%, respectively. Conservative treatment was the first choice (76.7%). The mean follow-up time was 29.3 ± 13.5 months. None of the patients had unplanned readmission due to worsening symptoms. Nine patients underwent coronary artery computed tomography reexamination after 10.3 ± 7.5 months, which showed complete recovery of SCIH. Eight patients were hospitalized for coronary angiography 6.4 ± 4.7 months later, which did not show any sign of SCIH. Spontaneous coronary intramural hematoma was most common in post-menopausal women with hypertension. Possibly, antiplatelet drugs should be avoided in SCIH. Waiting for the hematoma to heal was preferable and had a good prognosis.

A score system to predict no-reflow in primary percutaneous coronary intervention: The PIANO Score.

BACKGROUND: Angiographic no-reflow is associated with poor outcomes in patients with ST-segment elevation myocardial infarction (STEMI). We sought to develop and validate a score system to predict angiographic no-reflow in primary percutaneous coronary intervention (PCI). METHODS: ST-segment elevation myocardial infarction patients undergoing primary PCI were consecutively enrolled and were randomly divided into the training and validation set. Angiographic no-reflow was defined as thrombolysis in myocardial infarction (TIMI) flow grade 0 to 2 after PCI. In the training set, independent predictors were identified by logistic regression analysis, and a score system (PredIction of Angiographic NO-reflow, the PIANO score) was constructed based on the ß-coefficient of each variable. The established model was evaluated for discrimination and calibration. RESULTS: Angiographic no-reflow occurred in 362 (17.8%) of 2036 patients. Age ≥70 years, absence of pre-infarction angina, total ischaemic time ≥4 h, left anterior descending as culprit artery, pre-PCI TIMI flow grade ≤1 and pre-PCI TIMI thrombus score ≥4 were independent predictors of angiographic no-reflow. The PIANO score ranged from 0 to 14 points, yielding a concordance index of 0.857 (95% confidence interval: 0.833 to 0.880), with good calibration. In the high-risk (≥8 points) group, the probability of angiographic no-reflow phenomenon was 38.7%, while it was only 4.8% in the low-risk (<8 points) group. The score system performed well in the validation set. CONCLUSIONS: We establish and validate a score system based on six clinical variables to predict angiographic no-reflow in STEMI patients undergoing primary PCI, which may help choose the optimal individual treatment strategy.

Outcomes of contemporary versus conventional reverse controlled and antegrade and retrograde subintimal tracking in chronic total occlusion revascularization.

BACKGROUND: Chronic total occlusion (CTO) lesions remain technically challenging for percutaneous coronary intervention (PCI). The introduction of a retrograde approach has allowed marked improvement in the success rate of CTO recanalization. Reverse controlled anterograde and retrograde sub-intimal tracking (reverse CART) is the predominant retrograde wire crossing technique and can be broadly classified into three categories: (1) conventional (2) contemporary and (3) extended. The present study aimed to compare the safety and efficacy of conventional and contemporary reverse CART techniques. METHODS: From March 2015 to May 2020, 303 patients achieving successful retrograde guidewire crossing with conventional or contemporary reverse CART during CTO PCI were included in the study. The patient characteristics, procedural outcomes and in-hospital and 1-year clinical events were compared between the conventional and contemporary groups. RESULTS: The distributions of the baseline and angiographic characteristics were similar in both study arms, except the CTO lesions of the conventional group were more complex, as reflected by borderline significantly higher mean J-CTO scores (3.4 ± 0.7 vs. 3.3 ± 0.8; p = 0.059). Recanalization using contemporary reverse CART was associated with a short procedure time (189.8 ± 44.4 vs. 181.7 ± 37.3 min; p = 0.044) and decreased procedural complications, particularly target vessel perforation (3.6% vs. 0.6%; p = 0.063) and major side-branch occlusion (36.7% vs. 28.0%; p = 0.051). Technical and procedural success and the in-hospital and 1-year outcomes were not significantly different between the groups. CONCLUSIONS: Contemporary reverse CART is associated with favorably high efficiency and low-complication rates and carries a comparable success rate and 1-year clinical outcomes as conventional reverse CART.

Sexual Dysfunction and the Impact of Beta-Blockers in Young Males With Coronary Artery Disease.

Objective: We aimed to assess the association of erectile dysfunction (ED) with the extent of coronary atherosclerosis, and to examine whether revascularization and medication use have an impact on ED status in patients with early onset of coronary artery disease (EOCAD). Methods: International Index of Erectile Function (IIEF-5) was used to evaluate sexual function in 296 male patients with EOCAD (age, 39.9 ± 4.8 years), and 354 male controls (age, 40.6 ± 4.4 years). The extent of coronary atherosclerosis was measured by Gensini score. Endothelial function was evaluated by two vasomotor indexes including endothelin-1 (ET-1) and nitric oxide (NO) by ELISA. Results: ED was more frequent (57.8 vs. 31.1%, P < 0.001) and serious (IIEF-5 score:17.7 ± 6.0 vs. 21.6 ± 5.0, P < 0.001) among EOCAD patients than that among controls. IIEF-5 score was negatively correlated with Gensini score (r = -0.383, P < 0.001). The adjusted odds ratio (OR) for the presence of ED (EOCAD vs. controls) was 1.88 [95% confidential interval (CI), 1.12-3.18]. However, ET-1 and NO attenuated the association between ED and EOCAD (adjusted OR: 1.54, 95% CI: 0.84-2.80). IIEF-5 score increased after coronary revascularization in patients not on beta-blockers (18.71 ± 4.84 vs. 17.59 ± 6.05, P < 0.001) as compared with baseline, while stayed unchanged in the subgroup using beta-blockers (17.82 ± 5.12 vs. 17.70 ± 5.98, P = 0.09). Conclusions: ED was common in patients with EOCAD, and associated with the severity of coronary atherosclerosis. Endothelial dysfunction may be a pathophysiologic mechanism underlying both ED and EOCAD. Coronary revascularization confers a benefit in ED amelioration, while this effect did not appear in patients using beta-blocker.

Clinical Outcomes of Self-Made Polyurethane-Covered Stent Implantation for the Treatment of Coronary Artery Perforations.

OBJECTIVES: The present study aimed to investigate the short- and long-term clinical outcomes of self-made polyurethane-covered stents (PU-CS) in patients for the management of coronary artery perforation (CAP) during percutaneous coronary intervention (PCI). BACKGROUND: Coronary artery perforation is reckoned as a serious complication in PCI and associated with considerable morbidity and mortality. Covered stents have been used for treating the life-threatening CAP during PCI. But in some catheterization laboratories, no commercial CS is immediately available when there is an urgent need for CS to rescue the coronary rupture site. METHODS: We retrospectively identified 24 patients who underwent 31 self-made PU-CS implantations due to CAP in Zhongshan Hospital, Fudan University, from June 2015 to January 2020. RESULTS: The total procedural success rate of CS to seal the perforation was 79.2%. Nine patients (37.5%) developed cardiac tamponade, of which 8 patients (33.3%) underwent pericardiocentesis and 4 patients (16.7%) underwent cardiac surgeries. Except for 4 cardiac death cases (16.7%), none of myocardial infarction (MI), target lesion revascularization (TLR), and stent thrombosis (ST) was reported during hospital stay. Data from 22 patients (91.7%) were available at 610.4 ± 420.9 days of follow-up. Major adverse cardiac events (MACE) occurred in 6 patients (27.3%), including 5 cases of cardiac death and one TLR case. CONCLUSIONS: Self-made PU-CS demonstrates high rates of successful delivery and sealing of severe CAP during PCI. Although the in-hospital mortality remains high after PU-CS implantation, the long-term follow-up shows favorable clinical outcomes, indicating the feasibility of PU-CS in treating CAP.

Reattempt Percutaneous Coronary Intervention of Chronic Total Occlusions after Prior Failures: A Single-Center Analysis of Strategies and Outcomes.

OBJECTIVE: The initial recanalization rate of coronary chronic total occlusions (CTOs) is >85% when performed by experienced operators, but only 10% of prior failed CTO patients receive reattempted recanalization. This retrospective study analyzed the success rate and strategies used in reattempt percutaneous coronary intervention (PCI) of CTOs after prior failures. METHODS: Overall, 206 patients with 212 CTOs were enrolled. All patients with prior recanalization failures received reattempt PCIs from January 2015 to March 2019 at Zhongshan Hospital, Fudan University. Data on clinical factors (age, sex, comorbidities, left ventricular ejection fraction, history of cigarette usage, and revascularization), angiographic characteristics of CTOs (target lesion, Japanese Chronic Total Occlusion (J-CTO) score, the morphology of CTO lesions, and collateral channel scale), strategies (procedural approach and use of devices), and major adverse events were obtained and analyzed. RESULTS: The mean age of enrolled patients was 60.96 ± 12.36 years, with a male predominance of 90.3%. Of the patients, 47.1% had a prior myocardial infarction and 70.4% underwent stent implantation previously, while the in-stent occlusion rate was 6.6%. CTOs were primarily localized in the left anterior descending artery (43.9%) and the right coronary artery (43.9%). 80.7% of lesions were classified as very difficult (J-CTO score ≥3), and the overall success rate was 81.1%. In multivariable regression analysis, J-CTO score, collateral channel scale, application of coronary multispiral computed tomography angiography, dual injection, intravascular ultrasound, active greeting technique, parallel wiring, and CTO morphology were predictors of recanalization success. There were no significant differences in rates of procedural complications between the final recanalization success and failure groups. CONCLUSIONS: Recanalization of complex CTOs is associated with high success rate and low complication rates when performed by high-volume CTO operators and after multiple reattempts.

Procedural and In-hospital Outcomes of Rotational Atherectomy in Retrograde Coronary Chronic Total Occlusion Intervention.

Coronary chronic total occlusions (CTOs) are characterized by a high incidence of severe plaque calcifications, which are associated with a high use of the retrograde approach and a low success rate of percutaneous coronary intervention (PCI). However, the feasibility of rotational atherectomy (RA) in retrograde CTO-PCI remains unknown. The aim of the present study is to examine the safety and efficacy of RA in retrograde CTO-PCI. Consecutive patients (n = 129) who underwent RA during CTO-PCI were categorized into anterograde and retrograde groups according to the CTO crossing approach. The distributions of the baseline characteristics were similar in the 2 groups, but the lesion type was more complex (P = .001), and the starting burr size was smaller (P = .003) in the retrograde group than in the anterograde group. There was a trend of a higher incidence of procedural complications in the retrograde group than in the anterograde group (P = .054). Technical and procedural success and in-hospital outcomes were not significantly different between the 2 groups. In conclusion, RA was feasible in retrograde CTO PCI, but some specific precautions are required before and during the procedure. In addition, further investigation of the long-term outcomes of RA in retrograde CTO PCI is necessary.

Circulating CD34+VEGFR-2+ endothelial progenitor cells correlate with revascularization-mediated long-term improvement of cardiac function in patients with coronary chronic total occlusions.

BACKGROUND: Endothelial progenitor cells (EPCs) participate in angiogenesis and neocollateralization. This study assessed if circulating EPCs can predict long-term improvement of global left ventricular systolic function in patients with coronary chronic total occlusions (CTOs) underwent successful percutaneous coronary intervention (PCI). METHODS: In this single-center, prospective, observational study, 115 consecutive patients with CTOs were evaluated by standard transthoracic echocardiography (ECHO) before and 9-12 months after PCI. Numbers of circulating putative EPCs were determined by flow cytometry analysis of mononuclear cells isolated from peripheral blood samples drawn before and 72 h after PCI. RESULTS: At mean 11.3 ± 2.5 months post vs. before PCI (all P < .05): by SAQ-7 summary scores, angina frequency, physical limitation and quality of life scores were greater; by ECHO, LVEDd decreased and LVEF increased, which were more significant in patients with Rentrop grades 2/3 vs. 0/1. At 72 h post vs. before PCI, CD34+VEGFR-2+CD133- (0.82 ± 0.32 × 106/L vs. 1.00 ± 0.39 × 106/L, P = .003), CD34+VEGFR-2+CD133+ (0.24 ± 0.12 × 106/L vs. 0.27 ± 0.14 × 106/L, P = .028), and CD14+Tie2+VEGFR-2+ (6.60 ± 3.32 × 106/L vs. 7.82 ± 3.91 × 106/L, P = .006) cell numbers were lower. The baseline levels of CD34+VEGFR-2+cells (P = .001) and CD14+Tie2+VEGFR-2+cells (P < .001) were association with the grade of collateralization. In addition, the baseline and peri-procedural decrease of circulating CD34+VEGFR-2+ cells correlated with the increase of LVEF (P < .001, P < .001, respectively) and the decrease of LVEDd (P = .022, P = .029, respectively) at follow-up. CONCLUSIONS: In this small study, the baseline levels of circulating CD34+VEGFR-2+ EPCs and its reduction after successful revascularization of CTOs correlated with long-term improvement in global LV systolic function.

Hypoxia-challenged MSC-derived exosomes deliver miR-210 to attenuate post-infarction cardiac apoptosis.

BACKGROUND: Myocardial infarction (MI) is a major cause of death worldwide. Although percutaneous coronary intervention and coronary artery bypass grafting can prolong life, cardiac damage persists. In particular, cardiomyocytes have no regenerative capacity. Mesenchymal stem cells (MSCs) are attractive candidates for the treatment of MI. The manner by which MSCs exert a beneficial effect upon injured cells is a source of continued study. METHODS: After the isolation and identification of exosomes from MSCs, the expression of miR-210 was determined by microarray chip. Subsequently, gain- and loss-function approaches were conducted to detect the role of exosomes and exosomal-miR-210 in cell proliferation and apoptosis of cardiomyocytes, as well as the MI in vivo. Dual-Luciferase Report Gene System was used to demonstrate the target gene of miR-210. RESULTS: We tested the hypothesis that MSC-derived exosomes transfer specific miRNA to protect cardiomyocytes from apoptotic cell death. Interestingly, direct cardiac injection of MSC exosomes reduced infarct size and improved heart function after coronary ligation. In vitro, the MSC exosomes enhanced cardiomyocyte survival to hypoxia. Confirmation of exosome uptake in myocytes was confirmed. Dual-luciferase reporter assay implicated miR-210 as a mediator of the therapeutic effect and AIFM3 as a downstream target. Treatment with miR-210 overexpressing MSC exosomes improved myocyte protection to both in vitro and in vivo stress. Furthermore, the endogenous and exogenous miR-210 had the same therapeutic effects. CONCLUSION: These results demonstrated that the beneficial effects offered by MSC-exosomes transplantation after MI are at least partially because of excreted exosome containing mainly miR-210.

Circulating metabolites from the choline pathway and acute coronary syndromes in a Chinese case-control study.

BACKGROUND: Accumulating evidence shows that circulating levels of trimethylamine N-oxide, which is generated from the metabolism of dietary choline, may predict cardiovascular disease among Caucasians. Acute coronary syndrome (ACS), one common presentation of cardiovascular disease, is a spectrum of signs and symptoms due to acute decreased blood flow in the coronary arteries. The relationship between the metabolites from choline pathway and ACS remains unclear. We aimed to assess the associations of circulating metabolites from the choline pathway with ACS among a Chinese population, who consume a different dietary pattern than their Western counterparts. METHODS: We recruited 501 participants who were admitted to the Department of Cardiology, Zhongshan Hospital,Shanghai China between March 2017 and June 2018, including 254 ACS cases and 247 controls. Liquid chromatography-tandem mass spectrometry was used to measure circulating concentrations of metabolites in the choline pathway, including betaine, choline, trimethylamine, and trimethylamine N-oxide. A composite metabolite score using a weighted sum of these four metabolites, and the betaine/choline ratio were calculated. Multivariable logistic regressions were applied to estimate the association of metabolites with ACS, with adjustment of age, sex, body mass index, smoking index, history of diseases, and kidney function. RESULTS: After adjusting for traditional risk factors, per 1-standard deviation (SD) increment in choline was positively associated with the odds of ACS [odds ratio (OR), 95% confidence interval (CI), 1.77(1.44-2.18)], and the other metabolites were not associated with ACS at a statistical significance level. Compared with participants in the lowest quartile of the metabolite score, those in the highest quartile had higher odds of ACS [OR (95% CI), 3.18(1.85-5.54), p < 0.001 for trend]. Per 1-SD increment in metabolite score was positively associated with higher odds of ACS [OR (95% CI), 1.80 (1.37-2.40)], and per 1-SD increment in the betaine/choline ratio was inversely associated with the odds of ACS [OR (95% CI), 0.49 (0.39-0.60)]. CONCLUSIONS: Among our Chinese participants, trimethylamine N-oxide was not associated with ACS, while a composite metabolite score of metabolites from the choline pathway was associated with increased odds of ACS. The choline pathway metabolites may be related to the pathophysiology of ACS among Chinese.