Coronary slow flow and angiography-derived index of microcirculatory resistance as prognostic predictors in patients with angina and normal coronary arteries: a retrospective cohort study.

BACKGROUND: This study aims to investigate prognostic implications of coronary slow flow (CSF) and angiography-derived index of microcirculatory resistance (caIMR) in patients with angina and normal coronary arteries. METHODS: A total of 582 patients were enrolled with angiographically normal coronary arteries. caIMR was calculated using a commercial software. Patients were followed up for a median of 45 months. The primary endpoint was defined as major adverse cardiovascular events (MACEs) comprising death, myocardial infarction and readmission for angina or heart failure. RESULTS: CSF was diagnosed when TIMI grade 2 flow presented in at least one coronary artery. Multivariate analysis indicated TIMI-flow-based determination of CSF was not significantly associated with MACEs [hazard ratio (HR): 2.14; 95% confidence interval (CI): 0.87-5.31; p = 0.099), while caIMR >42 (HR: 2.53; 95% CI: 1.02-6.32; p = 0.047) were independent predictors of MACEs. Incorporation of caIMR improved the area under the curve from 0.587 to 0.642. CONCLUSIONS: caIMR was an independent prognostic factor of long-term cardiovascular events in patients with CSF. Evaluation of caIMR improved the risk stratification of patients with angiographically-normal coronary arteries.

Real-world performance of indobufen versus aspirin after percutaneous coronary intervention: insights from the ASPIRATION registry.

BACKGROUND: Indobufen is widely used in patients with aspirin intolerance in East Asia. The OPTION trial launched by our cardiac center examined the performance of indobufen based dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). However, the vast majority of patients with acute coronary syndrome (ACS) and aspirin intolerance were excluded. We aimed to explore this question in a real-world population. METHODS: Patients enrolled in the ASPIRATION registry were grouped according to the DAPT strategy that they received after PCI. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE) and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. Propensity score matching (PSM) was adopted for confounder adjustment. RESULTS: A total of 7135 patients were reviewed. After one-year follow-up, the indobufen group was associated with the same risk of MACCE versus the aspirin group after PSM (6.5% vs. 6.5%, hazard ratio [HR] = 0.99, 95% confidence interval [CI] = 0.65 to 1.52, P = 0.978). However, BARC type 2, 3, or 5 bleeding was significantly reduced (3.0% vs. 11.9%, HR = 0.24, 95% CI = 0.15 to 0.40, P < 0.001). These results were generally consistent across different subgroups including aspirin intolerance, except that indobufen appeared to increase the risk of MACCE in patients with ACS. CONCLUSIONS: Indobufen shared the same risk of MACCE but a lower risk of bleeding after PCI versus aspirin from a real-world perspective. Due to the observational nature of the current analysis, future studies are still warranted to further evaluate the efficacy of indobufen based DAPT, especially in patients with ACS. TRIAL REGISTRATION: Chinese Clinical Trial Register ( https://www.chictr.org.cn ); Number: ChiCTR2300067274.

Pinacidil ameliorates cardiac microvascular ischemia-reperfusion injury by inhibiting chaperone-mediated autophagy of calreticulin.

Calcium overload is the key trigger in cardiac microvascular ischemia-reperfusion (I/R) injury, and calreticulin (CRT) is a calcium buffering protein located in the endoplasmic reticulum (ER). Additionally, the role of pinacidil, an antihypertensive drug, in protecting cardiac microcirculation against I/R injury has not been investigated. Hence, this study aimed to explore the benefits of pinacidil on cardiac microvascular I/R injury with a focus on endothelial calcium homeostasis and CRT signaling. Cardiac vascular perfusion and no-reflow area were assessed using FITC-lectin perfusion assay and Thioflavin-S staining. Endothelial calcium homeostasis, CRT-IP3Rs-MCU signaling expression, and apoptosis were assessed by real-time calcium signal reporter GCaMP8, western blotting, and fluorescence staining. Drug affinity-responsive target stability (DARTS) assay was adopted to detect proteins that directly bind to pinacidil. The present study found pinacidil treatment improved capillary density and perfusion, reduced no-reflow and infraction areas, and improved cardiac function and hemodynamics after I/R injury. These benefits were attributed to the ability of pinacidil to alleviate calcium overload and mitochondria-dependent apoptosis in cardiac microvascular endothelial cells (CMECs). Moreover, the DARTS assay showed that pinacidil directly binds to HSP90, through which it inhibits chaperone-mediated autophagy (CMA) degradation of CRT. CRT overexpression inhibited IP3Rs and MCU expression, reduced mitochondrial calcium inflow and mitochondrial injury, and suppressed endothelial apoptosis. Importantly, endothelial-specific overexpression of CRT shared similar benefits with pinacidil on cardiovascular protection against I/R injury. In conclusion, our data indicate that pinacidil attenuated microvascular I/R injury potentially through improving CRT degradation and endothelial calcium overload.

Chronologic evolution and prognostic implications of impaired coronary flow after chronic total occlusion angioplasty.

Background: Although vessels have the potential to recover following successful recanalization of chronic total occlusion (CTO), evidence is limited about the clinical significance of slow flow (SF) phenomenon after recanalization. The aim of this study was to evaluate the determinants, development and prognostic impact of SF after percutaneous coronary intervention (PCI) for CTO. Methods: This was a retrospective cohort study, 500 patients were consecutively enrolled undergoing CTO PCI and consecutive follow-up angiography in Zhongshan Hospital, Fudan University, between 2015 and 2020. Coronary flow was assessed by corrected Thrombolysis in Myocardial Infarction (TIMI) frame count (CTFC). The association between SF and outcomes of CTO PCI was evaluated by analyzing the clinical, angiographic, and procedural characteristics. Results: SF was observed in 29 (5.8%) patients immediately after CTO PCI. Prior myocardial infraction, right coronary artery (RCA) revascularization and lack of bilateral collaterals were independent predictors of SF. SF was associated with increased risks of periprocedural myocardial infarction (PMI) [adjusted odds ratio (adOR): 4.12; 95% confidence interval (CI): 1.68-10.07; P=0.002] and target lesion restenosis (adOR: 2.50; 95% CI: 1.10-5.72; P=0.030). In patients with baseline left ventricular ejection fraction (LVEF) ≤60%, systolic improvement was compromised in the SF group (LVEF: 55.4%±9.6% in follow up vs. 52.1%±9.4% before CTO PCI, P=0.147) compared with that of the normal group (LVEF: 55.7%±9.3% vs. 51.6%±8.5%, P<0.001). Conclusions: SF has a significant influence on the prognosis of patients undergoing CTO PCI. Achieving normal coronary flow is essential in CTO revascularization.

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.

Prognostic implication of lipidomics in patients with coronary total occlusion undergoing PCI.

BACKGROUND: Predictors of prognosis in patients with coronary chronic total occlusion (CTO) undergoing elective percutaneous coronary intervention (PCI) have remained lacking. Lipidomic profiling enables researchers to associate lipid species with disease progression and may improve the prediction of cardiovascular events. METHODS: In the present study, 781 lipids were measured by targeted lipidomic profiling in 350 individuals (50 healthy controls, 50 patients with coronary artery disease and 250 patients with CTO). L1-regularized logistic regression was used to identify lipid species associated with adverse cardiovascular events and create predicting models, which were verified by 10-fold cross-validation (200 repeats). Comparisons were made between a traditional model constructed with clinical characteristics alone and a combined model built with both lipidomic data and traditional factors. RESULTS: Twenty-four lipid species were dysregulated exclusively in patients with CTO, most of which belonged to sphingomyelin (SM) and triacylglycerol (TAG). Compared with traditional risk factors, new model combining lipids and traditional factors had significantly improved performance in predicting adverse cardiovascular events in CTO patients after PCI (area under the curve, 0.870 vs. 0.726, p < .05; Akaike information criterion, 129 versus 156; net reclassification improvement, 0.312, p < .001; integrated discrimination improvement, 0.244, p < .001). Nomogram was built based on the incorporated model and proved efficient by Kaplan-Meier method. CONCLUSIONS: Lipidomic profiling revealed lipid species which may participate in the formation of CTO and could contribute to the risk stratification in CTO patients undergoing PCI.

Aortic valve calcification predicts poor outcomes after primary percutaneous coronary intervention.

BACKGROUND: Aortic valve calcification (AVC) is associated with increased cardiovascular risk in the general population. We sought to investigate whether AVC identified by transthoracic echocardiography could be a predictor of long-term adverse events after primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction. METHODS: Patients undergoing primary PCI were consecutively enrolled in this cohort study between 1 January 2009 and 31 December 31 2018. The presence of AVC was identified by transthoracic echocardiography one to three days after PCI. The primary endpoint was major adverse cardiovascular and cerebral events (MACCE) during follow-up. Propensity score matching was adopted to adjust for the baseline differences between groups. RESULTS: Of 2117 patients enrolled in the study, 566 (26.7%) were found to have AVC. Patients with AVC were older, more likely to be women, and disposed to have comorbidities and complex lesions. During a median follow-up period of 6.1 years, 699 cases of MACCE occurred, including 243 (42.9%) cases in patients with AVC and 456 (29.4%) cases in patients without AVC. After 1:1 propensity score matching, the presence of AVC increased the risk of MACCE (adjusted hazard ratio: 1.442, 95% confidence interval: 1.186 to 1.754, p < 0.001). This difference persisted when sensitivity and subgroup analyses were made. CONCLUSIONS: AVC identified by transthoracic echocardiography independently increased the long-term risk of MACCE after primary PCI in patients with acute myocardial infarction. This imaging feature will contribute to better risk stratification in this population.

A Simple Model to Predict Repeat Revascularization After Drug-Eluting Stent Implantation in Patients With Stable Coronary Artery Disease.

Repeat revascularization is still common in the era of drug-eluting stents (DES), especially for non-target lesions. However, few validated models exist to predict the need for revascularization. We aimed to develop and validate an easy-to-use predictive model for repeat revascularization after DES implantation in patients with stable coronary artery disease (CAD). A total of 1,653 stable CAD patients with angiographic follow-up after DES implantation were consecutively enrolled. Split-sample testing was adopted to develop and validate the model. In the training set, male, diabetes, number of target lesions, occlusion lesion, number of non-target lesions, recurrent angina, suboptimal low density lipoprotein-cholesterol level, and high lipoprotein (a) level were independent predictors of repeat revascularization using logistic regression analyses. The established model (Model 1) yielded a bias-corrected concordance index of 0.700 (95% confidence interval: 0.667 to 0.735), with good calibration. It also performed well in the validation set. Compared with the traditional empirical model only including recurrent angina (Model 2), Model 1 had better discriminative ability and clinical usefulness. In conclusion, we established and validated a simple model including 8 easily accessible variables to predict repeat revascularization after DES implantation in stable CAD patients, contributing to better risk stratification, decision making, and patient consultation.

Association between the magnitude of periprocedural myocardial injury and prognosis in patients undergoing elective percutaneous coronary intervention.

AIMS: This study aimed to investigate the prognostic implications of increased post-procedural cardiac troponin levels in patients undergoing elective percutaneous coronary intervention (PCI) and to define the threshold of prognostically relevant periprocedural myocardial injury (PMI). METHODS AND RESULTS: A total of 3249 patients with normal baseline troponin levels referred for elective PCI were enrolled and followed up for a median period of 20 months. The primary endpoint was major adverse cardiovascular events (MACEs) comprising all-cause death, myocardial injury (MI), and ischaemic stroke. Post-PCI high-sensitivity cardiac troponin T (hs-cTnT) >99% upper reference limit (URL) occurred in 78.3% of the patients and did not increase the risk of MACEs [adjusted hazard ratio (adHR) 1.00, 95% confidence interval (CI) 0.58-1.74, P = 0.990], nor did 'major PMI', defined as post-PCI hs-cTnT >5× URL (adHR 1.30, 95% CI 0.76-2.23, P = 0.340). Post-PCI troponin >8× URL, with an incidence of 15.2%, started to show an association with a higher risk of MACEs (adHR 1.89, 95% CI 1.06-3.37, P = 0.032), mainly driven by myocardial infarction (adHR 2.38, 95% CI 1.05-5.38, P = 0.037) and ischaemic stroke (adHR 3.35, 95% CI 1.17-9.64, P = 0.025). CONCLUSION: In patients with normal baseline troponin values undergoing elective PCI, PMI defined as hs-cTnT >8× URL after PCI was more appropriate for identifying patients with an increased risk of MACEs, which may help guide clinical practice in this population.

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.

Red Cell Distribution Width as a Marker of Periprocedural Myocardial Infarction in Patients with Elective Percutaneous Coronary Intervention.

We aimed to investigate whether red cell distribution width (RDW) was associated with periprocedural myocardial infarction (PMI) in patients undergoing elective percutaneous coronary intervention (PCI). Among 1723 consecutive patients undergoing elective PCI, a total of 230 (13.3%) met the diagnostic criteria of PMI. The high RDW (≥ 12.6%) group tended to have PMI (15.4% vs. 11.2%, P = 0.010). RDW was an independent predictor of PMI whether as a categorical variable (adjusted odds ratio = 1.442, 95% confidence interval = 1.088 to 1.911, P = 0.011) or a continuous variable (adjusted odds ratio = 1.236, 95% confidence interval = 1.079 to 1.415, P = 0.002). High RDW was also significantly associated with increased risk of major adverse cardiovascular events (MACE) during follow-up. However, anemia was not independently associated with PMI or MACE in the current study. In conclusion, RDW showed strong and independent association with PMI in patients undergoing elective PCI.

Incidence, predictors and clinical significance of periprocedural myocardial injury in patients undergoing elective percutaneous coronary intervention.

BACKGROUND: Although technological and equipment innovations have given rise to delicate and safe coronary intervention procedures, periprocedural myocardial injury (PMI) is still one of the common complications. The relationship between PMI, defined by various biomarker thresholds, and clinical prognosis remains controversial. We sought to assess the determinants and prognosis of PMI in patients with stable coronary artery disease (CAD) undergoing elective percutaneous coronary intervention (PCI). METHODS: Consecutive stable CAD patients with negative preoperative troponin T levels undergoing elective PCI in our hospital were enrolled from July 2017 to December 2017. PMI was defined as troponin T values >99th percentile upper reference limit (URL) within 16-24h post-PCI. The correlation of cardiovascular events and PMI was assessed after a median follow-up of 18 months. RESULTS: PMI occurred in 45.3% of the 1572 patients included, with 11.2% having troponin T levels elevated more than 5 times the URL after PCI. Independent risk factors for PMI were age ≥65 years, prior PCI, bifurcation lesion, stent number, and multivessel disease. During the follow-up period, patients with PMI had a higher incidence of unplanned revascularization [10.8% vs. 7.2%, adjusted hazard ratio (adHR) 1.40, 95% confidence interval (CI) 1.04-2.06; p=0.045] and target vessel revascularization (5.8% vs. 2.7%, adHR 1.90, 95% CI 1.06-3.38; p=0.030) than those without PMI. However, no significant impact of PMI on the risk of death and myocardial infarction was found. CONCLUSIONS: PMI defined by troponin T levels >99th percentile URL correlated with an increased risk of cardiovascular events in stable CAD patients undergoing elective PCI.

Cilostazol for Chinese Patients with Aspirin Intolerance after Coronary Drug-Eluting Stent Implantation.

BACKGROUND: Cilostazol-based dual antiplatelet therapy (DAPT) is widely used in patients with aspirin intolerance after coronary drug-eluting stent (DES) implantation in China. However, this empirical strategy is not recommended or even mentioned in Chinese or international guidelines due to a lack of evidence from large-scale studies. We aimed to explore the efficacy and safety of cilostazol-based DAPT in this special population. METHODS: In this cohort study, patients were grouped according to the DAPT strategy that they received after coronary DES implantation. The primary efficacy endpoint was major adverse cardiovascular and cerebrovascular events (MACCEs). Angiographic follow-up and major bleeding events were also recorded. RESULTS: A total of 918 patients receiving cilostazol-based DAPT due to aspirin intolerance were enrolled, matched with 918 patients receiving aspirin-based DAPT. After 15-month prospective follow-up, the cilostazol group had lower risk of MACCE (5.1% vs. 7.6%, propensity score adjusted hazard ratio = 0.671 [95% confidence interval 0.462-0.974], p = 0.036) compared with the aspirin group. Lower rate of coronary lesion progression was also found through follow-up angiography in the cilostazol group (17.4% vs. 23.6%, p = 0.022), especially in nontarget lesions (12.1% vs. 17.6%, p = 0.019). The two groups had the same risk of major bleeding events (0.8% vs. 0.4%, p = 0.364). CONCLUSION: In the current study, cilostazol is a good substitute for aspirin in patients who have aspirin intolerance but need DAPT after coronary DES implantation in China. However, large-scale randomized controlled trials were still required to further confirm its efficacy and safety.

[Determination of six cephalosporin residues in milk by QuEChERS-ultra high performance liquid chromatography-tandem mass spectrometry].

A simple, rapid and sensitive method for the simultaneous determination of six cephalosporin (cephalexin, cephapirin, cefotaxime, cefazolin, cefalonium and cefquinome) residues in milk was developed by QuEChERS coupled with ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).The milk samples were extracted with 10 mL acetonitrile containing 1%(v/v) acetic acid, and then centrifuged for 10 min.The supernatant was cleaned up with 100 mg C18 adsorbent powder.The analytes were separated on a reversed phase HSS T3 column (100 mm×2.1 mm, 1.8 µm) using acetonitrile and water containing 0.1%(v/v) formic acid as mobile phases with gradient elution.An electrospray ionization (ESI) source was used in the multiple reaction monitoring (MRM) mode.The analytes were quantified using an external standard method.The linear relationships of the six cephalosporins were good and the correlation coefficients (r) were greater than 0.999.The limits of detection (LODs) and the limits of quantification (LOQs) for the analytes were in the range of 0.2-0.6 µg/kg and 0.8-2 µg/kg, respectively.The recoveries of the target analytes were between 75.1% and 94.4% at spiked levels of 8, 16, 80 µg/kg.The relative standard deviations (RSDs) were no more than 8.3%(n=6).The method is simple and sensitive, and can be suitable for the analysis of the cephalosporin residues in milk.