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AimsTo investigate if recent technical and procedural developments in percutaneous coronary intervention (PCI) significantly influence outcomes in appropriately selected patients with three-vessel (3VD) coronary artery disease.Methods and resultsThe SYNTAX II study is a multicenter, all-comers, open-label, single arm study that investigated the impact of a contemporary PCI strategy on clinical outcomes in patients with 3VD in 22 centres from four European countries. The SYNTAX-II strategy includes: heart team decision-making utilizing the SYNTAX Score II (a clinical tool combining anatomical and clinical factors), coronary physiology guided revascularisation, implantation of thin strut bioresorbable-polymer drug-eluting stents, intravascular ultrasound (IVUS) guided stent implantation, contemporary chronic total occlusion revascularisation techniques and guideline-directed medical therapy. The rate of major adverse cardiac and cerebrovascular events (MACCE [composite of all-cause death, cerebrovascular event, any myocardial infarction and any revascularisation]) at one year was compared to a predefined PCI cohort from the original SYNTAX-I trial selected on the basis of equipoise 4-year mortality between CABG and PCI. As an exploratory endpoint, comparisons were made with the historical CABG cohort of the original SYNTAX-I trial. Overall 708 patients were screened and discussed within the heart team; 454 patients were deemed appropriate to undergo PCI. At one year, the SYNTAX-II strategy was superior to the equipoise-derived SYNTAX-I PCI cohort (MACCE SYNTAX-II 10.6% vs. SYNTAX-I 17.4%; HR 0.58, 95% CI 0.39–0.85, P = 0.006). This difference was driven by a significant reduction in the incidence of MI (HR 0.27, 95% CI 0.11–0.70, P = 0.007) and revascularisation (HR 0.57, 95% CI 0.37–0.9, P = 0.015). Rates of all-cause death (HR 0.69, 95% CI 0.27–1.73, P = 0.43) and stroke (HR 0.69, 95% CI 0.10–4.89, P = 0.71) were similar. The rate of definite stent thrombosis was significantly lower in SYNTAX-II (HR 0.26, 95% CI 0.07–0.97, P = 0.045).ConclusionAt one year, clinical outcomes with the SYNTAX-II strategy were associated with improved clinical results compared to the PCI performed in comparable patients from the original SYNTAX-I trial. Longer term follow-up is awaited and a randomized clinical trial with contemporary CABG is warranted.ClinicalTrials.gov IdentifierNCT02015832

IMPORTANCE Microvascular obstruction commonly affects patients with acute ST-segment elevation myocardial infarction (STEMI) and is associated with adverse outcomes. OBJECTIVE To determine whether a therapeutic strategy involving low-dose intracoronary fibrinolytic therapy with alteplase infused early after coronary reperfusion will reduce microvascular obstruction.

Background— An observational study determining the long-term impact of chronic kidney disease (CKD) on patients undergoing percutaneous coronary intervention at a tertiary cardiac referral center. CKD is associated with poor in-hospital outcomes after percutaneous coronary intervention, but its effect beyond 1 year, particularly in the drug-eluting stent (DES) era, has not been reported. Methods and Results— Baseline creatinine was available for 11 953 patients entered into a prospective registry (April 2000 to September 2007). Patients were stratified: those with or without at least moderate CKD (creatinine clearance, <60 mL/min). Follow-up data were obtained through linkage to a provincial registry. Kaplan–Meier analysis was performed. Cox multiple-regression analysis identified independent predictors of late mortality and major adverse cardiac events (MACE) and examined the association between DES use and late outcomes in the presence or absence of CKD. CKD was present in 3070 patients (25.7%). In-hospital mortality and MACE were significantly increased in CKD (3.34% versus 0.44%, P <0.001 and 5.73% versus 2.2%, P <0.001). Survival and MACE-free survival at 7 years were reduced (64.5�1.4% versus 89.4�0.5%, P <0.001; 44.0�1.4% versus 63.4�0.8%, P <0.001). CKD was an independent predictor of late mortality and MACE (hazard ratio [HR]: 2.18, CI: 1.90 to 2.49, P <0.0001; HR: 1.37, CI: 1.25 to 1.49, P <0.0001). DES use was associated with a significant reduction in both (HR: 0.71, CI: 0.60 to 0.83, P <0.0001; HR: 0.70, CI: 0.63 to 0.78, P <0.0001). In patients with CKD, DES use was associated with reduced revascularization (HR: 0.68, CI: 0.53 to 0.88, P =0.004) and reduced MACE (HR: 0.81, CI: 0.69 to 0.95, P =0.011) but not reduced mortality (HR: 0.85, CI: 0.69 to 1.05, P =0.1). Conclusion— In a large registry of “all comers” for percutaneous coronary intervention, CKD was an independent predictor of adverse late outcomes. DES use may be associated with improved long-term outcomes in this high-risk cohort, but further prospective studies are required.

Background— Extracellular matrix (ECM) remodeling is central to the development of restenosis after PTCA. Substantial evidence implicates transforming growth factor-β 1 (TGF-β 1 ), a regulator of ECM deposition by vascular cells, in its pathogenesis. TGF-β 3 reduces TGF-β 1 —induced ECM deposition in cutaneous wounds. We therefore investigated the effects of intracoronary expression of TGF-β 3 and TGF-β 1 on luminal loss after angioplasty. Methods and Results— Porcine coronary arteries received an adenovirus expressing TGF-β 3 , TGF-β 1 , or lacZ (β-galactosidase), or PBS only, at the site of angioplasty. Morphometric analysis 28 days after angioplasty confirmed reduced luminal loss in TGF-β 3 vessels (−0.65±0.10 mm 2 ) compared with lacZ (−1.18±0.19 mm 2 ) or PBS only (−1.19±0.17 mm 2 ; P =0.003). Luminal loss was not reduced in TGF-β 1 vessels (−1.02±0.19 mm 2 ; P =0.48). An increase in the external elastic lamina area in TGF-β 3 –treated vessels (+0.73±0.32 mm 2 ) contrasted with decreases in control vessels (mean, −0.53±0.17 mm 2 ; P =0.001) and TGF-β 1 vessels (−0.87±0.34 mm 2 ; P =0.003). Collagen content increased at the site of injury in TGF-β 3 –treated vessels (26.1±14.2%) but decreased in the lacZ (−22.8±6.6%) and PBS-only (−23.4±7.0%; P =0.002) groups and was not significantly changed in TGF-β 1 –treated vessels. Conclusions— Expression of TGF-β 3 inhibits constrictive remodeling after PTCA and reduces luminal loss. This is accompanied by increased adventitial collagen, which may act as an external “scaffold” preventing vessel constriction. These findings confirm the potential of gene therapies that modify ECM remodeling for prophylaxis of restenosis.

Aims The SYNTAX II study evaluated the impact of advances in percutaneous coronary intervention (PCI), integrated into a single revascularization strategy, on outcomes of patients with de novo three-vessel disease. The study employed decision-making utilizing the SYNTAX score II, use of coronary physiology, thin-strut biodegradable polymer drug-eluting stents, intravascular ultrasound, enhanced treatments of chronic total occlusions, and optimized medical therapy. Patients treated with this approach were compared with predefined patients from the SYNTAX I trial. Methods and results SYNTAX II was a multicentre, single-arm, open-label study of patients requiring revascularization who demonstrated clinical equipoise for treatment with either coronary artery bypass grafting (CABG) or PCI, predicted by the SYNTAX score II. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which included any revascularization. The comparators were a matched PCI cohort trial and a matched CABG cohort, both from the SYNTAX I trial. At 5 years, MACCE rate in SYNTAX II was significantly lower than in the SYNTAX I PCI cohort (21.5% vs. 36.4%, P &lt; 0.001). This reflected lower rates of revascularization (13.8% vs. 23.8%, P &lt; 0.001), and myocardial infarction (MI) (2.7% vs. 10.4%, P &lt; 0.001), consisting of both procedural MI (0.2% vs. 3.8%, P &lt; 0.001) and spontaneous MI (2.3% vs. 6.9%, P = 0.004). All-cause mortality was lower in SYNTAX II (8.1% vs. 13.8%, P = 0.013) reflecting a lower rate of cardiac death (2.8% vs. 8.4%, P &lt; 0.001). Major adverse cardiac and cerebrovascular events’ outcomes at 5 years among patients in SYNTAX II and predefined patients in the SYNTAX I CABG cohort were similar (21.5% vs. 24.6%, P = 0.35). Conclusions Use of the SYNTAX II PCI strategy in patients with de novo three-vessel disease led to improved and durable clinical results when compared to predefined patients treated with PCI in the original SYNTAX I trial. A predefined exploratory analysis found no significant difference in MACCE between SYNTAX II PCI and matched SYNTAX I CABG patients at 5-year follow-up.

Transcatheter aortic valve implantation (TAVI) is a proven treatment for life-threatening aortic valve disease, predominantly severe aortic stenosis. However, even among developed nations, access to TAVI is not uniform. The Valve for Life initiative was launched by the European Association of Percutaneous Cardiovascular Interventions in 2015 with the objective of improving access to transcatheter valve interventions across Europe. The UK has been identified as a country with low penetration of these procedures and has been selected as the fourth nation to be included in the initiative. Specifically, the number of TAVI procedures carried out in the UK is significantly lower than almost all other European nations. Furthermore, there is substantial geographical inequity in access to TAVI within the UK. As a consequence of this underprovision, waiting times for TAVI are long, and mortality among those waiting intervention is significant. This article reviews these issues, reports new data on access to TAVI in the UK and presents the proposals of the UK Valve for Life team to address the current problems in association with the British Cardiovascular Intervention Society.

Recombinant adenoviruses are employed widely for vascular gene transfer. Vascular smooth muscle cells (SMCs) are a relatively poor target for transgene expression after adenovirus-mediated gene delivery, however, even when expression is regulated by powerful, constitutive viral promoters. The major immediate-early murine cytomegalovirus enhancer/promoter (MIEmCMV) elicits substantially greater transgene expression than the human cytomegalovirus promoter (MIEhCMV) in all cell types in which they have been compared. The Woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) increases transgene expression in numerous cell lines, and fragments of the smooth muscle myosin heavy chain (SMMHC) promoter increase expression within SMC from heterologous promoters. We therefore, compared the expression of b-galactosidase after adenovirus-mediated gene transfer of lacZ under the transcriptional regulation of a variety of combinations of the promoters and enhancers described, in vitro and in porcine coronary arteries. We demonstrate that inclusion of WPRE and a fragment of the rabbit SMMHC promoter along with MIEmCMV increases b-galactosidase expression 90-fold in SMC in vitro and E40-fold in coronary arteries, compared with vectors in which expression is regulated by MIEhCMV alone. Expression cassette modification represents a simple method of improving adenovirus-mediated vascular gene transfer efficiency and has important implications for the development of efficient cardiovascular gene therapy strategies.