Chia-Hung Yang

SYNTAX score: an independent predictor of long-term cardiac mortality in patients with acute ST-elevation myocardial infarction.

IntroductionThis observational study aimed to determine whether the SYNergy between percutaneous coronary intervention (PCI) with TAXUS drug-eluting stent and the cardiac surgery (SYNTAX) score can act as an independent predictor for cardiac death on long-term follow-up in patients with acute ST-elevation myocardial infarction (STEMI). MethodsOne hundred and fifty-three patients admitted to the Chang Gung Memorial Hospital in Linkou because of acute STEMI from 1 January 2008 to 31 December 2009, who subsequently underwent a primary PCI, were included in this study. SYNTAX scores were calculated immediately after the primary PCI; and the prognostic value of the SYNTAX score in relation to cardiovascular events, which were defined as low-risk (SYNTAX score 0–22) and intermediate-risk to high-risk (SYNTAX score>22), was determined. Long-term follow-up was available in 141 patients (92%, mean follow-up duration of 30±11 months). ResultsBy Kaplan–Meier estimates, cardiac death-free survival was 99.1% in the low-risk group vs. 78.6% in the intermediate-risk to high-risk group at 42 months of follow-up (P<0.001). For all-cause death, the survival rate was 93.1% in the low-risk group vs. 78.6% in the intermediate-risk to high-risk group at 42 months of follow-up (P=0.002). Multivariate Cox-regression analysis showed that independent predictors of cardiac death were the SYNTAX score (odds ratio 15.90; 95% confidence interval 1.04–244.21) and symptom to onset-to-therapy interval (odds ratio 25.57; 95% confidence interval 1.00–655.96). ConclusionThe SYNTAX score is a strong independent predictor of cardiac death in intermediate-risk to high-risk patients with acute STEMI.

Circadian CLOCK Mediates Activation of Transforming Growth Factor-β Signaling and Renal Fibrosis through Cyclooxygenase 2

The circadian rhythm regulates blood pressure and maintains fluid and electrolyte homeostasis with central and peripheral clock. However, the role of circadian rhythm in the pathogenesis of tubulointerstitial fibrosis remains unclear. Here, we found that the amplitudes of circadian rhythm oscillation in kidneys significantly increased after unilateral ureteral obstruction. In mice that are deficient in the circadian gene Clock, renal fibrosis and renal parenchymal damage were significantly worse after ureteral obstruction. CLOCK-deficient mice showed increased synthesis of collagen, increased oxidative stress, and greater transforming growth factor-β (TGF-β) expression. TGF-β mRNA expression oscillated with the circadian rhythms under the control of CLOCK-BMAL1 heterodimers. The expression of cyclooxygenase 2 was significantly higher in kidneys from CLOCK-deficient mice with ureteral obstruction. Treatment with a cyclooxygenase 2 inhibitor celecoxib significantly improved renal fibrosis in CLOCK-deficient mice. Taken together, these data establish the importance of the circadian rhythm in tubulointerstitial fibrosis and suggest CLOCK/TGF-β signaling as a novel therapeutic target of cyclooxygenase inhibition.

The prognostic significance of SYNTAX score after early percutaneous transluminal coronary angioplasty for acute ST elevation myocardial infarction.

INTRODUCTION SYNergy between percutaneous coronary intervention (PCI) with TAXUS and Cardiac Surgery (SYNTAX) score, which is based on the characteristics of atherosclerotic lesions and the complexity of coronary artery anatomy, is useful for choosing an intervention strategy, but its prognostic significance for acute ST elevation of myocardial infarction (STEMI) remains unknown. This study aimed to redress this issue. METHODS Our observational study included 151 consecutive patients admitted for acute STEMI who underwent primary PCI between January 1, 2008 and December 31, 2009. The primary endpoint for analysis was 30-day cardiac death. RESULTS Among the 151 patients, cardiac death occurred in 10 (7%) within 30 days. After the first month, five patients died of non-cardiac causes, but no cardiac death occurred. Multivariate analysis showed that SYNTAX score (odds ratio [OR], 13.79, 95% confidence interval [CI], 1.24-153.38; p=0.033) and a symptom onset-to-therapy time interval >4 h (OR, 11.13; 95% CI, 1.08-114.42; p=0.043) were independent risk factors for 30-day mortality. The SYNTAX score cut-off for discriminating low and high risk was 22. CONCLUSIONS SYNTAX score is an independent predictor of short-term cardiac mortality in patients with acute STEMI.

CLOCK modulates survival and acute lung injury in mice with polymicrobial sepsis.

Polymicrobial sepsis is a potentially fatal condition and a significant burden on health care systems. Acute lung injury is the most common complication of sepsis and results in high mortality. However, there has been no recent significant progress in the treatment of sepsis or acute lung injury induced by sepsis. Here we show that mice deficient in the circadian protein CLOCK had better survival than wild-type mice after induction of polymicrobial sepsis by cecal ligation and puncture. Inflammatory cytokine production was attenuated and bacterial clearance was improved in CLOCK-deficient mice. Moreover, acute lung injury after induction of sepsis was significantly decreased in CLOCK-deficient mice. Genome-wide profiling analysis showed that inhibin signaling was reduced in CLOCK-deficient mice. These data establish the importance of circadian CLOCK-inhibin signaling in sepsis, which may have potential therapeutic implications.

Prognostic Impact of 9-Month High-Sensitivity C-Reactive Protein Levels on Long-Term Clinical Outcomes and In-Stent Restenosis in Patients at 9 Months after Drug-Eluting Stent Implantation

Introduction The level of 9-month high-sensitivity C-reactive protein (hsCRP) in predicting cardiovascular outcomes is scanty in patients at 9 months after receiving drug-eluting stent (DES) implantations. This study aims to evaluate the relationship between 9-month follow-up hsCRP levels and long-term clinical outcomes in patients at 9 months after receiving DES. Methods A total of 1,763 patients who received 9-month follow-up angiography were enrolled and grouped according to hsCRP level 9 months after the DES implantation: group I (718 patients, hsCRP<1.0 mg/L), group II (639 patients, 1.0≦hsCRP≦3.0 mg/L), and group III (406 patients, hsCRP>3.0 mg/L). Results Group III patients had a lower cardiovascular event-free survival rate than group I or II patients during a follow-up of 64±45 months (64.5% vs. 71.6% vs. 72.8%, respectively, p = 0.012). Multivariate analysis showed that a follow-up hsCRP level <3.0 mg/L was an independent predictor of a major adverse cardiovascular event (cardiac death, reinfarction, target lesion revascularization, stenting in a new lesion, or coronary bypass surgery). Group III patients had a higher restenosis rate (11.3% vs. 5.8% vs. 6.6%, respectively, p = 0.002) and loss index (0.21±0.32 vs. 0.16±0.24 vs. 0.18±0.28, respectively, p = 0.001) than group I or II patients in 9-month follow-up angiography. Conclusions A high 9-month follow-up hsCRP level is an independent predictor of long-term clinical cardiovascular outcomes in patients at 9 months after DES implantation. It is also associated with a higher restenosis rate, larger late loss and loss index at 9 months after DES implantation.

FTO modulates fibrogenic responses in obstructive nephropathy

Genome-wide association studies have shown that variants in fat mass and obesity-associated (FTO) gene are robustly associated with body mass index and obesity. These FTO variants are also associated with end stage renal disease and all-cause mortality in chronic kidney diseases. However, the exact role of FTO in kidneys is currently unknown. Here we show that FTO expression is increased after ureteral obstruction and renal fibrosis. Deficiency of the FTO gene attenuates the fibrogenic responses induced by ureteral obstruction in the kidney. Renal tubular cells deficient of FTO produce less α-SMA after TGF-β stimulation. FTO is indispensable for the extracellular matrix synthesis after ureteral obstruction in kidneys. Indeed, global gene transcriptions amplitude is reduced in FTO deficient kidneys after ureteral obstruction. These data establish the importance of FTO in renal fibrosis, which may have potential therapeutic implications.

Serum irisin levels are associated with adverse cardiovascular outcomes in patients with acute myocardial infarction

Irisin, a recently identified myokine, regulates mitochondrial function and energy expenditure. The concentration of irisin is significantly altered after ST-elevation myocardial infarction (STEMI). We hypothesized that serum irisin concentration is associated with adverse cardiovascular outcomes after myocardial infarction. Serum irisin concentrations were measured using enzyme-linked immunosorbent assay (ELISA) in 399 patients 28d after the onset of STEMI in a prospective single-center cohort study. We assessed the association between irisin concentrations and adverse cardiovascular events during a 3-year follow-up. The excess risks of cardiovascular mortality, stroke, heart failure, and revascularization were predominantly seen among those with the highest concentrations of irisin, with concentrations higher than 75th percentile of the overall distribution had a ~4-fold increase in risk (hazard ratio=3.96, 95% confidence interval 1.55 to 10.11, P<0.01). Our findings showed that serum concentrations of irisin are elevated in post-STEMI patients with increased risk for adverse cardiovascular events. Novel therapies targeting irisin may represent a new direction in the treatment of STEMI.

Review: The outcomes of different vessel diameter in patients receiving coronary artery stenting

Compared to bare metal stent (BMS) implantation, drug-eluting stents (DES) is significantly better in attenuating intimal hyperplasia and reducing the rate of revascularization. However, the requirement of prolonged dual antiplatelet therapy (DAPT) and the economic cost have been the major disadvantages of DES. Studies have shown that the use of DES in small vessels decrease revascularization rate, but the results in large vessels vary. Previous studies have shown that the extent of late loss is unrelated to vessel diameter, and that late loss is easily accommodated in large vessels, thus resulting in decreased clinical benefit of DES in this setting. No definite cut-off point value of the vessel size has yet been demonstrated. Series studies aimed at evaluating the clinical outcomes of DES versus BMS in large vessels, but their results have been controversial. In this review, we evaluate the latest studies on clinical outcomes for different vessel sizes and clinical conditions. Nonetheless, further large clinical trials are warranted to address the clinical results of newer stents in different size vessels, especially in large vessels.

Complete and incomplete revascularization in non-ST segment myocardial infarction with multivessel disease: long-term outcomes of first- and second-generation drug-eluting stents

The therapeutic effects of reperfusion strategies with complete revascularization (CR) or incomplete revascularization (IR) in non-ST segment myocardial infarction (NSTEMI) patients with multivessel disease (MVD) are controversial. In such patients, whether utilization of different generations of drug-eluting stents (DES) for IR or CR affect long-term major adverse cardiovascular events (MACE) is unknown. This study included 702 NSTEMI patients with MVD who received first-generation (1G) or second-generation (2G) DES. In multivariable analysis, chronic kidney disease, chronic total, 1G DES and IR were independent predictors of long-term MACE. In patients receiving 1G DES, no significant differences of MACE were observed between the IR and CR groups (39.1% vs. 36.2%, p = 0.854). However, in patients receiving 2G DES, significantly fewer MACE were observed in the CR group than in the IR group (3.7% vs. 10.2%, p = 0.002). Compared with patients receiving 1G DES for IR, those receiving 2G DES for IR and CR exhibited significantly lower risk of MACE (59% and 83% lower, respectively). CR could not provide clinical benefits over IR in NSTEMI patients with MVD receiving 1G DES. However, in patients receiving 2G DES, compared with IR, CR was associated with a lower risk of long-term MACE, which was mainly caused by low rates of non-TLR and any revascularization.

Comparison of the Acute and Long-Term Outcomes of Patients With Multivessel Coronary Artery Disease After Angiographic Complete and Incomplete Revascularization With Drug-Eluting Stents

BACKGROUND Data regarding the long-term outcomes of a large patient population with multivessel coronary artery disease (MV-CAD) after complete revascularization (CR) and incomplete revascularization (IR) with drug-eluting stent (DES) implantation are controversial. The objective of this study was to evaluate differences between the clinical outcomes of CR and IR in such patients.Methods and Results:A total of 1,502 patients with MV-CAD who received DES between April 2005 and August 2016 were enrolled in this study after propensity score matching. The CR group had 751 patients with 1,368 stents implanted in 1,215 lesions, and the IR group had 751 patients with 1,077 stents implanted in 948 lesions. The CR group had a similar rate of in-hospital major adverse cardiovascular events to the IR group (1.9% vs. 1.6%, P=0.844). Follow-up angiography at 9 months showed no significant difference between the 2 groups for restenosis. The CR group had a higher cardiovascular event-free survival rate than the IR group during a mean follow-up period of 71±62 months (81.8% vs. 72.0%, P<0.001). Kaplan-Meier survival analysis also showed better results in the CR group than in the IR group. CONCLUSIONS Angiographic CR was associated with more favorable long-term cardiovascular outcomes than angiographic IR in patients with MV-CAD after DES implantation.