A simple angio-based coronary flow assessment of culprit vessels in primary percutaneous coronary intervention is associated with long-term prognosis after ST-segment-elevation myocardial infarction.

BACKGROUND: Despite prompt reperfusion, the risk of adverse clinical outcomes following ST-segment-elevation myocardial infarction (STEMI) remains pronounced, owing partly to suboptimal reperfusion. However, coronary functional evaluation is seldom feasible during primary percutaneous coronary intervention (PPCI). We aimed to examine the clinical implication of a simple coronary assessment based on single-angiographic view (µQFR) during PPCI in discriminating impaired coronary flow and adverse outcomes for STEMI. METHODS: STEMI Patients undergoing successful PPCI were enrolled and followed up prospectively from 4 medical centers in China. Post-PPCI µQFR of culprit vessels were analyzed. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiac death, non-fatal MI, ischemia-driven target-vessel revascularization and readmission for heart failure. RESULTS: A total of 570 patients with STEMI were enrolled, and post-PCI µQFR was analyzable in 557 (97.7%) patients, with a median of 0.94. Patients with low post-PCI µQFR showed higher incidence of adverse outcomes than those with high µQFR, showing a 2.5-fold increase in the risk for MACE (hazard ratio: 2.51, 95% confidence intervals: 1.33 to 4.72; P = 0.004). Moreover, post-PCI µQFR significantly increased discriminant ability for the occurrence of MACE when added to traditional GRACE risk score for STEMI (integrated discrimination improvement: 0.029; net reclassification index: 0.229; P < 0.05). CONCLUSIONS: A low µQFR of culprit vessel in PPCI is independently associated with worse clinical outcomes in patients with STEMI. The single-angiographic-view-based coronary evaluation is a feasible tool for discriminating poor prognosis and could serve as a valuable complement in risk stratification for STEMI.

Microvascular and Prognostic Effect in Lesions With Different Stent Expansion During Primary PCI for STEMI: Insights From Coronary Physiology and Intravascular Ultrasound.

Background: While coronary stent implantation in ST-elevation myocardial infarction (STEMI) can mechanically revascularize culprit epicardial vessels, it might also cause distal embolization. The relationship between geometrical and functional results of stent expansion during the primary percutaneous coronary intervention (pPCI) is unclear. Objective: We sought to determine the optimal stent expansion strategy in pPCI using novel angiography-based approaches including angiography-derived quantitative flow ratio (QFR)/microcirculatory resistance (MR) and intravascular ultrasound (IVUS). Methods: Post-hoc analysis was performed in patients with acute STEMI and high thrombus burden from our prior multicenter, prospective cohort study (ChiCTR1800019923). Patients aged 18 years or older with STEMI were eligible. IVUS imaging, QFR, and MR were performed during pPCI, while stent expansion was quantified on IVUS images. The patients were divided into three subgroups depending on the degree of stent expansion as follows: overexpansion (>100%), optimal expansion (80%-100%), and underexpansion (<80%). The patients were followed up for 12 months after PCI. The primary endpoint included sudden cardiac death, myocardial infarction, stroke, unexpected hospitalization or unplanned revascularization, and all-cause death. Results: A total of 87 patients were enrolled. The average stent expansion degree was 82% (in all patients), 117% (in overexpansion group), 88% (in optimal expansion), and 75% (in under-expansion). QFR, MR, and flow speed increased in all groups after stenting. The overall stent expansion did not affect the final QFR (p = 0.08) or MR (p = 0.09), but it reduced the final flow speed (-0.14 cm/s per 1%, p = 0.02). Under- and overexpansion did not affect final QFR (p = 0.17), MR (p = 0.16), and flow speed (p = 0.10). Multivariable Cox analysis showed that stent expansion was not the risk factor for MACE (hazard ratio, HR = 0.97, p = 0.13); however, stent expansion reduced the risk of MACE (HR = 0.95, p = 0.03) after excluding overexpansion patients. Overexpansion was an independent risk factor for no-reflow (HR = 1.27, p = 0.02) and MACE (HR = 1.45, p = 0.007). Subgroup analysis shows that mild underexpansion of 70%-80% was not a risk factor for MACE (HR = 1.11, p = 0.08) and no-reflow (HR = 1.4, p = 0.08); however, stent expansion <70% increased the risk of MACE (HR = 1.36, p = 0.04). Conclusions: Stent expansion does not affect final QFR and MR, but it reduces flow speed in STEMI. Appropriate stent underexpansion of 70-80% does not seem to be associated with short-term prognosis, so it may be tolerable as noninferior compared with optimal expansion. Meanwhile, overexpansion and underexpansion of <70% should be avoided due to the independent risk of MACEs and no-reflow events.

Non-stenting strategy is not inferior to stent implantation in patients with acute ST-segment elevated myocardial infarction and high thrombus burden and intermediate stenotic culprit lesion.

BACKGROUND: According to European Society of Cardiology (ESC) as well as American College of Cardiology/American Heart Association (ACC/AHA) guidelines, primary stenting is recommended for patients with acute ST-segment elevation myocardial infarction (STEMI); however, in-stent thrombosis is a life-threatening early adverse event that could lead to acute myocardial infarction (AMI) or even cardiac death. On the other hand, in-stent restenosis is a late adverse event that could result in recurrent readmission and revascularization. We compared a non-stenting (NS) strategy to a stenting (S) strategy in terms of incidence of major adverse cardiac events (MACEs) for patients with acute STEMI and high thrombus burden. METHODS: We performed a post hoc analysis of our prior multicenter, prospective cohort study (ChiCTR1800019923) among 51 eligible patients with acute STEMI and high thrombus burden. All participants received percutaneous coronary intervention (PCI) with a deferred-stenting strategy (second procedure performed within 48-72 h after primary PCI). Either NS or S strategies were carried out among patients. Primary outcomes were follow-ups of MACEs at 1, 3, 6, and 12 months. Intravenous ultrasound (IVUS) and quantitative flow ratio (QFR) evaluation were performed. RESULTS: In our post hoc analysis of 51 patients (21 with NS and 30 with S), baseline clinical and interventional characteristics were well matched between the 2 groups, to the exception of culprit lesion length. Incidence of MACEs was not significantly different between the 2 strategies in-hospital (P=0.56) and in follow-ups at 1 (P=0.41), 3 (free of events), 6 (P=0.71), and 12 (P=0.68) months. Culprit lesions of NS tended to be "low-risk" [minimum lumen area (MLA) 4.27±1.02 vs. 3.80±1.32 mm2, P=0.36] and plaque burden (70.79%±6.46% vs. 76.97%±6.76%, P=0.03) when compared with culprit lesions of S in IVUS evaluation. Evaluation of QFR showed more sufficient physiological reperfusion improvement with NS than with S [two-dimensional (2D) QFR: 0.85±0.09 vs. 0.79±0.13, P=0.10 and 3D QFR: 0.86±0.08 vs. 0.78±0.15, P=0.02]. CONCLUSIONS: The NS strategy did not increase MACEs in-hospital and at 1, 3, 6, and 12 months. The NS can be a safe option when meeting certain criteria for patients with STEMI and a high thrombus burden.

The outcomes in STEMI patients with high thrombus burden treated by deferred versus immediate stent implantation in primary percutaneous coronary intervention: a prospective cohort study.

BACKGROUND: No-/slow-reflow indicates worse outcomes in ST-elevation myocardial infarction (STEMI) patients with high thrombus burden. We examined whether deferred stenting (DS) strategy reduces no-/slow-reflow or major adverse cardiovascular events (MACEs) in primary percutaneous coronary intervention (pPCI) for patients with acute STEMI and high thrombus burden. METHODS: We performed an open-label, multi-center, prospective cohort study among eligible patients with acute STEMI and high thrombus burden who further received pPCI. All participants received PCI with DS (second procedure performed within 48-72 h) or immediate-stenting (IS) strategy. The primary outcome was the incidence of no-/slow-reflow. We evaluated MACEs and bleeding events during hospitalization and at 30- and 90-day follow-ups. RESULTS: We recruited 245 patients to this study, including 51 with DS and 194 with IS. Baseline clinical characters were comparable between the 2 strategies. Incidence of no-/slow-reflow defined by thrombolysis in myocardial infarction (TIMI) flow grade was not significantly different between the 2 strategies [DS: 5 (9.8%), IS: 33 (17.0%), P=0.21]. No-/slow-reflow by TIMI myocardial perfusion grade (TMPG) was less prevalent in DS [20 (39.2%) vs. 107 (55.2%), P=0.04]. No significant differences were found in recurrence of myocardial infarction (P=0.56), cardiac death (P=0.37), all-cause mortality (P=0.37), heart failure-induced readmission (P=0.35), or bleeding (P=0.61) between the 2 strategies in-hospital, and at 30- and 90-day follow-up. CONCLUSIONS: In STEMI patients with high thrombus burden who underwent pPCI, DS strategy reduced no-/slow-reflow of microcirculation. However, DS strategy did not reduce incidence of MACEs or bleeding.

Lipoprotein (a) as a residual risk factor for atherosclerotic renal artery stenosis in hypertensive patients: a hospital-based cross-sectional study.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-c) has been proven to be a risk factor for atherosclerotic cardiovascular disease (CVD), while lipoprotein (a) (Lp(a)) is a residual risk factor for CVD, even though LDL-c is well controlled by statin use. Importantly, the role of Lp(a) in atherosclerotic renal artery stenosis (ARAS) is still unknown. METHODS: For this hospital-based cross-sectional study, patients who simultaneously underwent coronary and renal angiography were examined. ARAS was defined as a 50% reduction in the cross-sectional (two-dimensional plane) area of the renal artery. Data were collected and compared between ARAS and non-ARAS groups, including clinical history and metabolite profiles. Univariate analysis, three tertile LDL-c-based stratified analysis, and multivariate-adjusted logistic analysis were conducted, revealing a correlation between Lp(a) and ARAS. RESULTS: A total of 170 hypertensive patients were included in this study, 85 with ARAS and 85 with non-RAS. Baseline information indicated comparability between the two groups. In the univariate and multivariate analysis, common risk factors for atherosclerosis were not significantly different. Stratified analysis of LDL-c revealed a significant increase in the incidence of ARAS in patients who had high Lp(a) concentrations at low LDL-c levels (odds ratio (OR): 4.77, 95% confidence interval (CI): 1.04-21.79, P = 0.044). Further logistic analysis with adjusted covariates also confirmed the result, indicating that high Lp(a) levels were independently associated with ARAS (adjusted OR (aOR): 6.14, 95%CI: 1.03-36.47, P = 0.046). This relationship increased with increasing Lp(a) concentration based on a curve fitting graph. These results were not present in the low and intermediate LDL-c-level groups. CONCLUSION: In hypertensive patients who present low LDL-c, high Lp(a) was significantly associated with atherosclerotic renal artery stenosis and thus is a residual risk factor.

Safe Hydration Volume to Prevent Contrast-induced Acute Kidney Injury and Worsening Heart Failure in Patients With Heart Failure and Preserved Ejection Fraction After Cardiac Catheterization.

Few studies have investigated the efficacy and safety of hydration to prevent contrast-induced acute kidney injury (CI-AKI) and worsening heart failure (WHF) after cardiac catheterization in heart failure and preserved ejection fraction (HFpEF; HF and EF ≥50%) patients. We recruited 1206 patients with HFpEF undergoing cardiac catheterization with periprocedural hydration volume/weight (HV/W) ratio data and investigated the relationship between hydration volumes and risk of CI-AKI and WHF. Incidence of CI-AKI was not significantly reduced in individuals with higher HV/W [quartile (Q) 1, Q2, Q3, and Q4: 9.7%, 10.2%, 12.7%, and 12.2%, respectively; P = 0.219]. Multivariate analysis indicated that higher HV/W ratios were not associated with decreased CI-AKI risks [Q2 vs. Q1: odds ratio (OR), 0.95; Q3 vs. Q1: OR, 1.07; Q4 vs. Q1: OR, 0.92; all P > 0.05]. According to multivariate analysis, higher HV/W significantly increased the WHF risk (Q4 vs. Q1: adjusted OR, 8.13 and 95% confidence interval, 1.03-64.02; P = 0.047). CI-AKI and WHF were associated with a significantly increased risk of long-term mortality (mean follow-up, 2.33 years). For HFpEF patients, an excessively high hydration volume might not be associated with lower risk of CI-AKI but may increase the risk of postprocedure WHF.

Association of lipoprotein(a) with long-term mortality following coronary angiography or percutaneous coronary intervention.

BACKGROUND: There is no consistent evidence to suggest the association of plasma lipoprotein(a) (Lp[a]) with long-term mortality in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI). HYPOTHESIS: Level of Lp(a) is associated with long-term mortality following CAG or PCI. METHODS: We enrolled 1684 patients with plasma Lp(a) data undergoing CAG or PCI between April 2009 and December 2013. The patients were divided into 2 groups: a low-Lp(a) group (Lp[a] <16.0 mg/dL; n = 842) and a high-Lp(a) group (Lp[a] ≥16.0 mg/dL; n = 842). RESULTS: In-hospital mortality was not significantly different between the high and low Lp(a) groups (0.8% vs 0.5%, respectively; P = 0.364). During the median follow-up period of 1.95 years, the high-Lp(a) group had a higher long-term mortality than did the low-Lp(a) group (5.8% vs 2.5%, respectively; P = 0.003). After adjustment of confounders, multivariate Cox regression analysis revealed that a higher Lp(a) level was an independent predictor of long-term mortality (hazard ratio: 1.96, 95% confidence interval: 1.07-3.59, P = 0.029). CONCLUSIONS: Our data suggested that an elevated Lp(a) level was significantly associated with long-term mortality following CAG or PCI. However, additional larger multicenter studies will be required to investigate the predictive value of Lp(a) levels and evaluate the benefit of controlling Lp(a) levels for patients undergoing CAG or PCI.

Concomitant coronary and renal revascularization improves left ventricular hypertrophy more than coronary stenting alone in patients with ischemic heart and renal disease.

Percutaneous transluminal renal artery stenting (PTRAS) has been proved to have no more benefit than medication alone in treating atherosclerotic renal artery stenosis (ARAS). Whether PTRAS could improve left ventricular hypertrophy (LVH) and reduce adverse events when based on percutaneous coronary intervention (PCI) for patients with coronary artery disease (CAD) and ARAS is still unclear. A retrospective study was conducted, which explored the effect of concomitant PCI and PTRAS versus PCI alone for patients with CAD and ARAS complicated by heart failure with preserved ejection fraction (HFpEF). A total of 228 patients meeting inclusion criteria were divided into two groups: (1) the HFpEF-I group, with PCI and PTRAS; (2) the HFpEF-II group, with PCI alone. Both groups had a two-year follow-up. The left ventricular mass index (LVMI) and other clinical characteristics were compared between groups. During the follow-up period, a substantial decrease in systolic blood pressure (SBP) was observed in the HFpEF-I group, but not in the HFpEF-II group. There was marked decrease in LVMI in both groups, but the HFpEF-I group showed a greater decrease than the HFpEF-II group. Regression analysis demonstrated that PTRAS was significantly associated with LVMI reduction and fewer adverse events after adjusting for other factors. In HFpEF patients with both CAD and ARAS, concomitant PCI and PTRAS can improve LVH and decrease the incidence of adverse events more than PCI alone. This study highlights the beneficial effect of ARAS revascularization, as a new and more aggressive revascularization strategy for such high-risk patients.

Arg97² insulin receptor substrate-1 inhibits endothelial nitric oxide synthase expression in human endothelial cells by upregulating microRNA-155.

The dysregulation of nitric oxide (NO) synthesis attributable to the abnormal expression/activity of endothelial NO synthase (eNOS) is considered to be a major characteristic of insulin-resistant states, as well as an essential contributor to the pathogenesis of cardiovascular diseases. The Arg972 insulin receptor substrate-1 (IRS-1) is associated with insulin resistance. In the present study, we investigated the association between Arg972 IRS-1 and eNOS expression/activity in human subjects and in primary cultures of human endothelial cells. Data from 832 human subjects revealed that heterozygous and homozygous Arg972 IRS-1 carriers had significantly lower levels of plasma eNOS and nitrite/nitrate than the homozygous wild-type (WT) IRS-1 carriers. Human umbilical vein endothelial cells (HUVECs) established from delivering mothers expressing heterozygous Arg972 IRS-1 had significantly lower eNOS expression/activity and higher miR-155 levels than those expressing WT homozygous IRS-1. The overexpression of IRS-1 and Arg972 IRS-1 in the HUVECs, respectively, decreased and increased the miR-155 expression level. In addition, the overexpression of IRS-1 in the HUVECs significantly increased eNOS expression; this effect was reversed by transfection with mature miR-155 mimic or treatment with the selective phosphatidylinositol-3 kinase (PI3K) inhibitor, BKM120. On the other hand, the overexpression of Arg972 IRS-1 markedly decreased eNOS expression and this effect was reversed by transfection with antagomir-155. On the whole, our in vivo data demonstrate that Arg972 IRS-1 is associated with decreased plasma eNOS and nitrite/nitrate levels in human subjects. Our in vitro data demonstrate that Arg972 IRS-1 inhibits eNOS expression in human endothelial cells by upregulating miR-155 expression through the impairment of PI3K signaling. The present study provides new insight into the pathophysiological role of Arg972 IRS-1 in cardiovascular diseases.

Decrease of glomerular filtration rate may be attributed to the microcirculation damage in renal artery stenosis.

BACKGROUND: The decrease of glomerular filtration rate has been theoretically supposed to be the result of low perfusion in renal artery stenosis (RAS). But the gap between artery stenosis and the glomerular filtration ability is still unclear. METHODS: Patients with selective renal artery angiogram were divided by the degree of renal artery narrowing, level of estimated glomerular filtration rate (eGFR), respectively. The different levels of eGFR, renal microcirculation markers, and RAS severity were compared with each other, to determine the relationships among them. RESULTS: A total of 215 consecutive patients were enrolled in the prospective cohort study. Concentrations of microcirculation markers had no significant difference between RAS group (RAS ≥ 50%) and no RAS group (RAS < 50%) or did not change correspondingly to RAS severity. The value of eGFR in RAS group was lower than that in the no RAS group, but it did not decline parallel to the progressive severity of RAS. The microcirculation markers presented integral difference if grouped by different eGFR level with negative tendency, especially that plasma cystatin C (cysC) and urinary microalbumin to creatinine ratio (mACR) increased with the deterioration of eGFR, with strong (r = -0.713, P < 0.001) and moderate (r = -0.580, P < 0.001) correlations. In the subgroup analysis of severe RAS (RAS ≥ 80%), the levels of plasma cysC and urinary mACR demonstrated stronger negative associations with eGFR, (r = -0.827, P < 0.001) and (r = -0.672, P < 0.001) correlations, respectively. CONCLUSIONS: Severity of RAS could not accurately predict the value of eGFR, whereas microcirculation impairment may substantially contribute to the glomerular filtration loss in patients with RAS.