Natural History and Clinical Outcomes After ST-Segment Elevation Myocardial Infarction Without Stent Insertion.

After restoration of coronary perfusion in patients presenting with ST-segment elevation myocardial infarction (STEMI), discrete severe stenotic coronary lesions are not always apparent. There remains ambiguity whether drug-eluting stent (DES) insertion or initial medical management is best practice. We sought to assess short-term clinical outcomes in patients presenting with STEMI without initial stent insertion. Patients who underwent percutaneous coronary intervention for STEMI between 2014 and 2020 were prospectively enrolled and assessed for inclusion. Patients presenting with in-stent restenosis or stent thrombosis, or who did not survive to hospital discharge were excluded. Of 13,871 patients presenting, 456 (3.3%) were treated without initial stenting. These patients were older than those treated with DES (66.1 ± 13.6 vs 62.3 ± 12.4 years, p <0.001), had higher rates of diabetes (23.5% vs 16.0%, p <0.001) and previous revascularization with either percutaneous coronary intervention (14.0% vs 7.3%, p <0.001) or coronary artery bypass graft (3.5% vs 1.8%, p = 0.008). Thirty-day mortality was elevated in patients treated without stenting compared to those receiving DES (4.2% vs 0.9%, p <0.001), as were rates of myocardial infarction (1.3% vs 0.5%, p = 0.026) and major adverse cardiac events (10.5% vs 2.4%, p <0.001). After propensity matching, a trend toward increased mortality remained (4.2% vs 2.0%, p = 0.055). In conclusion, a no-stenting initial strategy, compared with DES insertion, is associated with increased 30-day mortality in those presenting with STEMI without severe stenosis. These data suggest when appropriate, current-generation DES insertion should be undertaken.

Differential predictability for high-risk plaque characteristics between fractional flow reserve and instantaneous wave-free ratio.

To evaluate the differential associations of high-risk plaque characteristics (HRPC) with resting or hyperemic physiologic indexes (instantaneous wave-free ratio [iFR] or fractional flow reserve [FFR]), a total of 214 vessels from 127 patients with stable angina or acute coronary syndrome who underwent coronary computed tomography angiography (CCTA) and invasive physiologic assessment were investigated. HPRC were classified into quantitative (minimal luminal area < 4 mm2 or plaque burden ≥ 70%) and qualitative features (low attenuation plaque, positive remodeling, napkin ring sign, or spotty calcification). Vessels with FFR ≤ 0.80 or iFR ≤ 0.89 had significantly higher proportions of HRPC than those with FFR > 0.80 or iFR > 0.89, respectively. FFR was independently associated with both quantitative and qualitative HRPC, but iFR was only associated with quantitative HRPC. Both FFR and iFR were significantly associated with the presence of ≥ 3 HRPC, and FFR demonstrated higher discrimination ability than iFR (AUC 0.703 vs. 0.648, P = 0.045), which was predominantly driven by greater discriminating ability of FFR for quantitative HRPC (AUC 0.832 vs. 0.744, P = 0.005). In conclusion, both FFR and iFR were significantly associated with CCTA-derived HRPC. Compared with iFR, however, FFR was independently associated with the presence of qualitative HRPC and showed a higher predictive ability for the presence of ≥ 3 HRPC.

Protein-Specific Signal Peptides for Mammalian Vector Engineering.

Expression of recombinant proteins in mammalian cell factories relies on synthetic assemblies of genetic parts to optimally control flux through the product biosynthetic pathway. In comparison to other genetic part-types, there is a relative paucity of characterized signal peptide components, particularly for mammalian cell contexts. In this study, we describe a toolkit of signal peptide elements, created using bioinformatics-led and synthetic design approaches, that can be utilized to enhance production of biopharmaceutical proteins in Chinese hamster ovary cell factories. We demonstrate, for the first time in a mammalian cell context, that machine learning can be used to predict how discrete signal peptide elements will perform when utilized to drive endoplasmic reticulum (ER) translocation of specific single chain protein products. For more complex molecular formats, such as multichain monoclonal antibodies, we describe how a combination of in silico and targeted design rule-based in vitro testing can be employed to rapidly identify product-specific signal peptide solutions from minimal screening spaces. The utility of this technology is validated by deriving vector designs that increase product titers ≥1.8×, compared to standard industry systems, for a range of products, including a difficult-to-express monoclonal antibody. The availability of a vastly expanded toolbox of characterized signal peptide parts, combined with streamlined in silico/in vitro testing processes, will permit efficient expression vector re-design to maximize titers of both simple and complex protein products.

Characteristics of conventional high-risk coronary plaques and a novel CT defined thin-cap fibroatheroma in patients undergoing CCTA with stable chest pain.

BACKGROUND: Coronary computed tomography angiography (CCTA) can identify high-risk coronary plaque types. However, the inter-observer variability for high-risk plaque features, including low attenuation plaque (LAP), positive remodelling (PR), and the Napkin-Ring sign (NRS), may reduce their utility, especially amongst less experienced readers. METHODOLOGY: In a prospective study, we compared the prevalence, location and inter-observer variability of both conventional CT-defined high-risk plaques with a novel index based on quantifying the ratio of necrotic core to fibrous plaque using individualised X-ray attenuation cut-offs (the CT-defined thin-cap fibroatheroma - CT-TCFA) in 100 patients followed-up for 7 years. RESULTS: In total, 346 plaques were identified in all patients. Seventy-two (21%) of all plaques were classified by conventional CT parameters as high-risk (either NRS or PR and LAP combined), and 43 (12%) of plaques were considered high-risk using the novel CT-TCFA definition of (Necrotic Core/fibrous plaque ratio of >0.9). The majority (80%) of the high-risk plaques (LAP&PR, NRS and CT-TCFA) were located in the proximal and mid-LAD and RCA. The kappa co-efficient of inter-observer variability (k) for NRS was 0.4 and for PR and LAP combined 0.4. While the kappa co-efficient of inter-observer variability (k) for the new CT-TCFA definition was 0.7. During follow-up, patients with either conventional high-risk plaques or CT-TCFAs were significantly more likely to have MACE (Major adverse cardiovascular events) compared to patients without coronary plaques (p value 0.03 & 0.03, respectively). CONCLUSION: The novel CT-TCFA is associated with MACE and has improved inter-observer variability compared with current CT-defined high-risk plaques.

Inter-software and inter-scan variability in measurement of epicardial adipose tissue: a three-way comparison of a research-specific, a freeware and a coronary application software platform.

OBJECTIVES: Epicardial adipose tissue (EAT) is a proposed marker of cardiovascular risk; however, clinical application may be limited by variability in post-processing software platforms. We assessed inter-vendor agreement of EAT volume (EATv) and attenuation on both contrast-enhanced (CE) and non-contrast CT (NCT) using a standard coronary CT reporting software (Vitrea), an EAT research-specific software (QFAT) and a freeware imaging software (OsiriX). METHODS: Seventy-six consecutive patients undergoing simultaneous CE and NCT had complete volumetric EAT measurement. Between-software, within-software NCT vs. CE, and inter- and intra-observer agreement were evaluated with analysis by ANOVA (with post hoc adjustment), Bland-Altman with 95% levels of agreement (LoA) and intraclass correlation coefficient (ICC). RESULTS: Mean EATv (freeware 53 ± 31 mL vs. research 93 ± 43 mL vs. coronary 157 ± 64 mL) and attenuation (freeware - 72 ± 25 HU vs. research - 75 ± 3 HU vs. coronary - 61 ± 10 HU) were significantly different between all vendors (ANOVA p < 0.001). EATv was consistently higher in NCT vs. CE for all software packages, with most reproducibility found in research software (bias 26 mL, 95% LoA: 2 to 56 mL), compared to freeware (bias 11 mL 95% LoA: - 46 mL to 69 mL) and coronary software (bias 10 mL 95% LoA: - 127 to 147 mL). Research software had more comparable NCT vs. CE attenuation (- 75 vs. - 72 HU) compared to freeware (- 72 vs. - 57 HU) and coronary (- 61 vs. - 39 HU). Excellent inter-observer agreement was seen with research (ICC 0.98) compared to freeware (ICC 0.73) and coronary software (ICC 0.75) with narrow LoA on Bland-Altman analysis. CONCLUSION: There are significant inter-vendor differences in EAT assessment. Our study suggests that research-specific software has better agreement and reproducibility compared to freeware or coronary software platforms. KEY POINTS: • There are significant differences between EAT volume and attenuation values between software platforms, regardless of scan type. • Non-contrast scans routinely have higher mean EAT volume and attenuation; however, this finding is only consistently seen with research-specific software. • Of the three analyzed packages, research-specific software demonstrates the highest reproducibility, agreement, and reliability for both inter-scan and inter-observer agreement.

Peri-Coronary Adipose Tissue Is a Predictor of Stent Failure in Patients Undergoing Percutaneous Coronary Intervention.

PURPOSE: Coronary inflammation is postulated as a driver of atherosclerosis and dysfunctional arterial healing which may trigger stent failure. Pericoronary adipose tissue (PCAT) attenuation, detected on computer tomography coronary angiography (CTCA), is an emerging non-invasive marker of coronary inflammation. This propensity matched study assessed the utility of both lesion specific (PCATLesion) and standardized PCAT attenuation as assessed in the proximal RCA (PCATRCA) as a predictor of stent failure in patients undergoing elective percutaneous coronary intervention. This is the first study to our knowledge that assesses the association of PCAT with stent failure. METHODS: Patients undergoing CTCA assessment for coronary artery disease with subsequent stent insertion within 60 days and repeat coronary angiography for any clinical reason within 5 years were included in the study. Stent failure was defined as binary restenosis of >50 % on quantitative coronary angiography analysis or stent thrombosis. Both PCATLesion and PCATRCA was assessed utilizing semi-automated proprietary software on baseline CTCA. Patients with stent failure were propensity matched utilizing age, sex, cardiovascular risk factors and procedural characteristics. RESULTS: One hundred and fifty-one patients met inclusion criteria. Of these, 26 (17.2 %) had study-defined failure. A significant difference in PCATLesion attenuation between patients with and without failure was observed (-79.0 ± 12.6 vs. -85.9 ± 10.3HU, p = 0.035). There was no significant difference in PCATRCA attenuation between the two groups (-79.5 ± 10.1 vs -81.0 ± 12.3HU, p = 0.50). Univariate regression analysis showed PCATLesion attenuation was independently associated with stent failure (OR 1.06, 95 % CI 1.01-1.12, P = 0.035). CONCLUSIONS: Patients with stent failure exhibit significantly increased PCATLesion attenuation at baseline. These data suggest that baseline plaque inflammation may be an important driver for coronary stent failure.

Colchicine in the Management of Acute Coronary Syndrome: A Meta-analysis.

INTRODUCTION: Colchicine, thought to exert its effect via reduction of inflammation, has recently been studied in patients following acute coronary syndromes (ACS). We performed a meta-analysis of all available randomized controlled trials (RCTs) in this high-risk cohort, evaluating efficacy and safety. METHODS: MEDLINE, PubMed, EMBASE, clinical trial registries, and select conference proceedings were searched for RCTs comparing colchicine to placebo in patients following ACS. The primary outcome was trial-defined major adverse cardiovascular events (MACE). Secondary endpoints included stroke, myocardial infarction (MI), all-cause and cardiovascular death, and urgent revascularization. Analysis was performed at the longest available clinical follow-up. RESULTS: Two RCTs with a pooled sample size of 5540 patients with 2778 (50.1%) receiving colchicine and 2762 (49.9%) placebo were included. In order to maximize consistency, composite efficacy endpoints between trials were modified. Compared to placebo, patients receiving colchicine had reduction in study-defined composite endpoint (5.5% vs. 7.6%) OR 0.67 (95% CI 0.46-0.98, p = 0.04, I2 = 46%). Similarly, there was a significant reduction in cerebrovascular accidents (OR 0.31, 95% CI 0.14-0.69, p = 0.004, I2 = 0%) and repeat revascularization OR 0.36 (95% CI 0.14-0.90, p = 0.03, I2 = 54%). There was no difference between cardiovascular death (OR 0.92, 95% CI 0.52-1.62, p = 0.78, I2 = 0%), non-cardiovascular death OR 1.27 (95% CI 0.72-2.24, p = 0.41, I2 = 0%), MI at longest available follow-up OR 0.89 (95% CI 0.67-1.17, p = 0.39, I2 = 0%) or resuscitated cardiac arrest OR 0.88 (95% CI 0.32-2.43, p = 0.81, I2 = 0%) in those receiving colchicine. CONCLUSIONS: These data suggest colchicine, in addition to guideline-directed medical therapy following acute coronary syndrome reduces MACE, cerebrovascular accidents, and rates of urgent revascularization at 2 years of follow-up.

Diagnostic performance of quantitative flow ratio, non-hyperaemic pressure indices and fractional flow reserve for the assessment of coronary lesions in severe aortic stenosis.

Background: Quantitative flow ratio (QFR) may be used to assess the functional significance of coronary lesions. Only limited validation exists for this technology in the setting of severe aortic stenosis. Methods: A prospective study was performed on patients who were being considered for transcatheter aortic valve implantation. QFR analysis was performed (Medis Medical Imaging System, Leiden, The Netherlands) and compared to invasive measurements of haemodynamic assessment [fractional flow reserve (FFR), instantaneous wave-free ratio (iFR), diastolic pressure ratio during the wave-free period (dPR) and distal arterial pressure/arterial pressure (Pd/Pa)]. Results: A total of 35 patients were included in the study. Mean age was 75.5±6.5 and mean aortic valve gradient was 44.3±11.8 mmHg. There were 57 vessels analysed. The mean FFR was 0.83±0.10 and 22 vessels (39%) had a functionally significant FFR ≤0.80. QFR demonstrated a discriminatory power to predict functionally significant FFR [area under the receiver operating characteristic curve (AUC), 0.92; 95% confidence interval (CI): 0.84 to 1.00], representing a sensitivity of 73%, specificity of 91%, positive predictive value of 84%, negative predictive value of 84% and an accuracy of 84%. QFR also demonstrated a discriminatory power to predict functionally significant iFR ≤0.89 (AUC =0.92; 95% CI: 0.85 to 0.99), dPR ≤0.89 (AUC =0.90; 95% CI: 0.83 to 0.98) and Pd/Pa ≤0.92 (AUC =0.89; 95% CI: 0.80 to 0.97). Conclusions: QFR demonstrates acceptable diagnostic performance in patients with severe aortic stenosis when both FFR and non-hyperaemic pressure indices are used as reference standards.

Prognostic Value of Exercise Capacity in Kidney Transplant Candidates.

Background Exercise stress testing for cardiovascular assessment in kidney transplant candidates has been shown to be a feasible alternative to pharmacologic methods. Exercise stress testing allows the additional assessment of exercise capacity, which may have prognostic value for long-term cardiovascular outcomes in pre-transplant recipients. This study aimed to evaluate the prognostic value of exercise capacity on long-term cardiovascular outcomes in kidney transplant candidates. Methods and Results We retrospectively evaluated exercise capacity in 898 consecutive kidney transplant candidates between 2013 and 2020 who underwent symptom-limited exercise stress echocardiography for pre-transplant cardiovascular assessment. Exercise capacity was measured by age- and sex-predicted metabolic equivalents (METs). The primary outcome was incident major adverse cardiovascular events, defined as cardiac death, non-fatal myocardial infarction, and stroke. Cox proportional hazard multivariable modeling was performed to define major adverse cardiovascular events predictors with transplantation treated as a time-varying covariate. A total of 429 patients (48%) achieved predicted METs. During follow-up, 93 (10%) developed major adverse cardiovascular events and 525 (58%) underwent transplantation. Achievement of predicted METs was independently associated with reduced major adverse cardiovascular events (hazard ratio [HR] 0.49; [95% CI 0.29-0.82], P=0.007), as was transplantation (HR, 0.52; [95% CI 0.30-0.91], P=0.02). Patients achieving predicted METs on pre-transplant exercise stress echocardiography had favorable outcomes that were independent (HR, 0.78; [95% CI 0.32-1.92], P=0.59) and of similar magnitude to subsequent transplantation (HR, 0.97; [95% CI 0.42-2.25], P=0.95). Conclusions Achievement of predicted METs on pre-transplant exercise stress echocardiography confers excellent prognosis independent of and of similar magnitude to subsequent kidney transplantation. Future studies should assess the benefit on exercise training in this population.

Engineering of the CMV promoter for controlled expression of recombinant genes in HEK293 cells.

Expression of recombinant genes in HEK293 cells is frequently utilized for production of recombinant proteins and viral vectors. These systems frequently employ the cytomegalovirus (CMV) promoter to drive recombinant gene transcription. However, the mechanistic basis of CMV-mediated transcriptional activation in HEK293 cells is unknown and consequently there are no strategies to engineer CMV for controlled expression of recombinant genes. Extensive bioinformatic analyses of transcription factor regulatory elements (TFREs) within the human CMV sequence and transcription factor mRNAs within the HEK293 transcriptome revealed 80 possible regulatory interactions. Through in vitro functional testing using reporter constructs harboring discrete TFREs or CMV deletion variants we identified key TFRE components and clusters of TFREs (cis-regulatory modules) within the CMV sequence. Our data reveal that CMV activity in HEK293 cells is a function of the promoters various constituent TFREs including AhR:ARNT, CREB, E4F, Sp1, ZBED1, JunB, c-Rel, and NF-κB. We also identified critical Sp1-dependent upstream activator elements near the transcriptional start site that were required for efficient transcription and YY1 and RBP-Jκ binding sites that mediate transrepression. Our study shows for the first time that novel, compact CMV-derived promoters can be engineered that exhibit up to 50% higher transcriptional efficiency (activity per unit DNA sequence) or 14% increase in total activity compared to the wild-type counterpart.

Bioinformatic Design of Dendritic Cell-Specific Synthetic Promoters.

Next-generation DNA vectors for cancer immunotherapies and vaccine development require promoters eliciting predefined transcriptional activities specific to target cell types, such as dendritic cells (DCs), which underpin immune response. In this study, we describe the de novo design of DC-specific synthetic promoters via in silico assembly of cis-transcription factor response elements (TFREs) that harness the DC transcriptional landscape. Using computational genome mining approaches, candidate TFREs were identified within promoter sequences of highly expressed DC-specific genes or those exhibiting an upregulated expression during DC maturation. Individual TFREs were then screened in vitro in a target DC line and off-target cell lines derived from skeletal muscle, fibroblast, epithelial, and endothelial cells using homotypic (TFRE repeats in series) reporter constructs. Based on these data, a library of heterotypic promoter assemblies varying in the TFRE composition, copy number, and sequential arrangement was constructed and tested in vitro to identify DC-specific promoters. Analysis of the transcriptional activity and specificity of these promoters unraveled underlying design rules, primarily TFRE composition, which govern the DC-specific synthetic promoter activity. Using these design rules, a second library of exclusively DC-specific promoters exhibiting varied transcriptional activities was generated. All DC-specific synthetic promoter assemblies exhibited >5-fold activity in the target DC line relative to off-target cell lines, with transcriptional activities ranging from 8 to 67% of the nonspecific human cytomegalovirus (hCMV-IE1) promoter. We show that bioinformatic analysis of a mammalian cell transcriptional landscape is an effective strategy for de novo design of cell-type-specific synthetic promoters with precisely controllable transcriptional activities.

Agreement Between iFR and Other Non-Hyperaemic Pressure Ratios in Severe Aortic Stenosis.

BACKGROUND: Instantaneous wave-free ratio (iFR) can reliably assess the physiological significance of coronary artery disease (CAD). Previous studies have demonstrated its interchangeability with other non-hyperaemic pressure ratios (NHPR), but there is no data exploring whether this association is maintained in patients with severe aortic stenosis (AS). METHODS: Forty-two patients (67 lesions) with severe AS were recruited and underwent invasive pressure-wire assessment. Data were extracted to calculate iFR, resting Pd/Pa, diastolic pressure ratios (DPR and dPR), and Diastolic Hyperaemia-Free Ratio (DFR). iFR was then compared with other NHPR to determine agreement and accuracy. RESULTS: Mean aortic gradient and dimensionless index were 44.3 ± 11.6 mmHg and 0.23 ± 0.04, respectively. Of the 67 vessels, 57% were LAD, 15% LCx, 13% RCA and 12% other. There was strong positive correlation between iFR and all other NHPR, including Pd/Pa (r = 0.91, p < 0.001), DPR (r = 0.99, p < 0.001), dPR (r = 0.97, p < 0.001) and DFR (r = 0.98, p < 0.001). While Bald-Altman analysis demonstrated that Pd/Pa and DFR were numerically different from iFR, ROC analyses demonstrated iFR ≤0.89 was accurately identified by all NHPRs; Pd/Pa (AUC = 0.965, 95% CI [0.928-0.994]), DPR (AUC = 1.000, 95% CI [1.000-1.000]), dPR (AUC = 0.974, 95% CI [0.937-1.000]), DFR (AUC = 0.989, 95% CI [0.968-1.000]). CONCLUSION: In patients with severe AS, all the included NHPR in this analysis accurately predicted iFR < 0.89. These data should reassure clinicians that use of alternative NHPR to iFR is reasonable when assessing the physiological significance of CAD in patients with severe AS.

Trans-Myocardial Blood Interleukin-6 Levels Relate to Intracoronary Imaging-Defined Features of Plaque Vulnerability and Predict Procedure-Induced Myocardial Infarction.

BACKGROUND: Intravascular imaging has defined various vulnerable plaque (VP) phenotypes that predict future clinical events. Atherosclerosis is an inflammatory process and inflammation, measured by systemic biomarkers can also predict events and anti-inflammatory therapy is beneficial. We were interested to assess the relationship between plaque phenotypes and key inflammatory biomarkers, measured close to the coronary. METHODS: Ninety-two patients scheduled for elective percutaneous coronary intervention (PCI) underwent virtual histology intravascular ultrasound, optical coherence tomography, pressure wire and blood sampling from the guide catheter (GC), coronary sinus (CS) to determine trans-myocardial gradient (TMG = CS-GC) and from peripheral blood. Procedure related troponin release was assessed at 6-hours post-PCI from peripheral venous blood. Biomarker data were analysed and compared with coronary data. RESULTS: Interleukin (IL)-6 was associated with increased levels of tumour necrosis factor (TNF)-α and C-reactive protein (CRP) and the pre-PCI IL-6 TMG correlated with plaque features of vulnerability: plaque burden - PB (r = 0.253, p = 0.04) and minimal lumen area - MLA (r = -0.438, p = 0.007), although no relationship existed for thin-capped fibroatheroma defined by either imaging modality. Peripheral IL-6 levels had no correlation with post PCI troponin, although the pre-PCI IL-6 TMG was related (r = 0.334, p = 0.006), as was PB (r = 0.27, p = 0.029). CONCLUSION: IL-6 TMG pre-PCI correlates with plaque burden and MLA that have been shown to predict future clinical events and is correlated with post-PCI troponin release. These associations were not apparent from peripheral blood and suggest that local coronary biomarker signatures may help further define vulnerability and risk.

Coronary imaging of cardiac allograft vasculopathy predicts current and future deterioration of left ventricular function in patients with orthotopic heart transplantation.

BACKGROUND: Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) improve sensitivity of cardiac allograft vasculopathy (CAV) detection compared to invasive coronary angiography (ICA), but their ability to predict clinical events is unknown. We determined whether severe CAV detected with ICA, IVUS, or OCT correlates with graft function. METHODS: Comparison of specific vessel parameters between IVUS and OCT on 20 patients attending for angiography 12-24 months post-orthotopic heart transplant. Serial left ventricular ejection fraction (EF) was recorded prospectively. RESULTS: Analyzing 55 coronary arteries, OCT and IVUS correlated well for vessel CAV characteristics. A mean intimal thickness (MIT)OCT  > .25 mm had a sensitivity of 86.7% and specificity of 74.3% at detecting Stanford grade 4 CAV. Those with angiographically evident CAV had significant reduction in graft EF over 7.3 years follow-up (median ΔEF -2% vs +1.5%, P = .03). Patients with MITOCT  > .25 mm in at least one vessel had a lower median EF at time of surveillance (57% vs 62%, P = .014). Two MACEs were noted. CONCLUSION: Imaging with OCT correlates well with IVUS for CAV detection. Combined angiography and OCT to screen for CAV within 12-24 months of transplant predicts concurrent and future deterioration in graft function.

Diabetes mellitus is independently associated with early stent thrombosis in patients undergoing drug eluting stent implantation: Analysis from the Victorian cardiac outcomes registry.

BACKGROUND: Diabetes mellitus (DM) is a predictor of restenosis and late stent thrombosis (ST) in patients undergoing percutaneous coronary intervention (PCI) with drug-eluting-stents (DES). Real-world data on rates of early ST is lacking. We compared clinical outcomes of patients with and without DM from the Victorian cardiac outcomes registry. METHODS: Consecutive patients undergoing PCI with DES were analyzed with primary outcome being ST at 30-days. Secondary outcomes including major adverse cardiovascular events (MACE) and all-cause mortality. RESULTS: Of 43,209 patients included, 9730 (22.5%) had DM. At 30 days, DM was independently associated with higher rates of early ST (0.7% vs. 0.5%) OR 1.41 (95% confidence interval; 1.05-1.87, p = 0.02), MACE (4.1% vs. 3.5%, p = 0.004) and mortality (1.9% vs. 1.5%, p = 0.01). Increased risk was not simply due to treatment. Patients with DM requiring insulin were equally affected in regard to MACE (4.7% vs. 3.9%, p = 0.069) and mortality (1.9%, vs. 1.8%, p = 0.746). On National Death Index linkage, patients with DM had increased all-cause mortality over five-year follow-up (OR 1.69 CI 1.55-1.83, p = < 0.001). CONCLUSION: In this large real-world-registry, DM was an independent predictor of early ST, MACE and mortality at 30 days. These data suggest additional therapeutic strategies are required to reduce the risk of early complications in patients with DM undergoing PCI with DES.