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Ellis grade III coronary artery perforations (G3-CAP) remain a life-threatening complication of percutaneous coronary intervention (PCI), with high morbidity and mortality and lack of consensus regarding optimal treatment strategies. We reviewed all PCIs performed in 10 European centers from 1993 to 2019 recording all G3-CAP along with management strategies, in-hospital and long-term outcome according to Device-related perforations (DP) and Guidewire-related perforations (WP). Among 106,592 PCI (including 7,773 chronic total occlusions), G3-CAP occurred in 311 patients (0.29%). DP occurred in 194 cases (62.4%), more commonly in proximal segments (73.2%) and frequently secondary to balloon dilatation (66.0%). WP arose in 117 patients (37.6%) with chronic total occlusions guidewires involved in 61.3% of cases. Overall sealing success rate was 90.7% and usually required multiple maneuvers (80.4%). The most commonly adopted strategies to obtain hemostasis were prolonged balloon inflation (73.2%) with covered stent implantation (64.4%) in the DP group, and prolonged balloon inflation (53.8%) with coil embolization (41%) in the WP group. Procedural or in-hospital events arose in 38.2% of cases: mortality was higher after DP (7.2% vs 2.6%, p = 0.05) and acute stent thrombosis 3-fold higher (3.1% vs 0.9%, p = 0.19). At clinical follow-up, median 2 years, a major cardiovascular event occurred in one-third of cases (all-cause mortality 8.2% and 7.1% respectively, without differences between groups). In conclusion, although rare and despite improved rates of adequate perforation sealing G3-CAP cause significant adverse events. DP and WP result in different patterns of G3-CAP and management strategies should be based on this classification.

Background Spontaneous coronary artery dissection (SCAD) is a rare condition, mainly affecting young women. Cases in male patients are rare, especially with recurrence. Case summary A 59-year-old male non-elite athlete presented as an ST-elevation myocardial infarction following a 5-km run. Urgent coronary angiogram was normal, but cardiac magnetic resonance showed a myocardial infarction. Four years later, he experienced similar chest pain with no ST-elevation on electrocardiogram and a mild troponin rise. Urgent coronary angiogram was initially thought normal but subsequent close inspection confirmed a Type 2b SCAD. Cardiac magnetic resonance showed a small additional myocardial infarction contained within an area of acute myocardial oedema. Discussion Spontaneous coronary artery dissection is more common in young women compared to men and recurrent dissection has been rarely reported in the literature. Cohort studies have shown the rate of recurrent dissection to be 13–16%, but most of the patients in these cohorts are female. Poor data exists on the best treatment of SCAD in men, but given the presence of intramural thrombus, dual antiplatelet therapy was discontinued on the presumption that it may exacerbate an intramural bleeding process.

Background: The pathophysiology and trajectory of multiorgan involvement in post-COVID-19 syndrome is uncertain. Methods: A prospective, multicenter, longitudinal, cohort study involving post-COVID-19 patients enrolled in-hospital or early post-discharge (visit 1) and re-evaluated 28-60 days post-discharge (visit 2). Multisystem investigations included chest computed tomography with pulmonary and coronary angiography, cardiovascular and renal magnetic resonance imaging, digital electrocardiography, and multisystem biomarkers. The primary outcome was the adjudicated likelihood of myocarditis.Results: 161 patients (mean age 55 years, 43% female) and 27 controls with similar age, sex, ethnicity, and vascular risk factors were enrolled from 22 May 2020 to 2 July 2021 and had a primary outcome evaluation. Compared to controls, at 28-60 days post-discharge, patients with COVID-19 had persisting evidence of cardio-renal involvement, systemic inflammation, and hemostasis pathway activation. Myocarditis was adjudicated as being not likely (n=17; 10%), unlikely (n=56; 35%), probable (n=67; 42%) or very likely (n=21; 13%). Acute kidney injury (odds ratio, 95% confidence interval: 3.40 (1.13, 11.84); p=0.038) and low hemoglobin A1c (0.26 (0.07, 0.87); p=0.035) were multivariable associates of adjudicated myocarditis. During convalescence, compared to controls, COVID-19 was associated with worse health-related quality of life (EQ5D-5L) (pConclusions: The illness trajectory of COVID-19 includes persisting cardio-renal inflammation, lung damage and hemostasis activation. Adjudicated myocarditis occurred in one in eight hospitalized patients and was associated with impairments in health status, physical and psychological wellbeing during community convalescence. Public registration: ClinicalTrials.gov identifier is NCT04403607.

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 < 0.001). This reflected lower rates of revascularization (13.8% vs. 23.8%, P < 0.001), and myocardial infarction (MI) (2.7% vs. 10.4%, P < 0.001), consisting of both procedural MI (0.2% vs. 3.8%, P < 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 < 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.

Introduction Intravascular ultrasound (IVUS) is a useful adjunct to guide percutaneous coronary intervention (PCI). Correlating IVUS images with angiographic findings can be challenging. We evaluated the utility of a novel co-registration system for IVUS and coronary angiography. Methods and results A 3-D virtual catheter trajectory was constructed from separate angiographic imaging runs using bespoke software. Intravascular ultrasound images were obtained using a commercially available mechanical rotational transducer with motorized pullback. Co-registration of ultrasound and angiographic images was then performed retrospectively based on the length of pullback, the 3-D trajectory and the start position of the catheter. Validation was performed in a spherical phantom model and in vivo in the coronary circulation of patients undergoing coronary angiography and intravascular imaging for clinical purposes. 111 paired angiographic and IVUS runs were performed in 3 phantom models. The differences between the reference length and the length measured on the 3D reconstructed path was −0.01 ± 0.40 mm. Intra-observer variability was 0.4%. We enrolled 25 patients in 3 European hospitals and performed 35 co-registration attempts with an 86% success rate. 71 landmarks were selected by the first operator, 68 by the second. Differences between angiographic and IVUS landmarks were −0.22 ± 0.72 mm and 0.05 ± 1.01 mm, respectively. Inter-observer variability was 0.23 ± 0.63 mm. Conclusion We present a novel method for the co-registration of IVUS and coronary angiographic images. This system performed well in a phantom model and using images obtained from the human coronary circulation. Classifications Innovation, intravascular ultrasound, other technique

Background: The risk of cardiovascular disease and mortality in salt-sensitive patients with diabetes mellitus and uncontrolled nocturnal hypertension is high. The SACRA (Sodium-Glucose Cotransporter 2 [SGLT2] Inhibitor and Angiotensin Receptor Blocker [ARB] Combination Therapy in Patients With Diabetes and Uncontrolled Nocturnal Hypertension) study investigated changes in blood pressure (BP) with empagliflozin plus existing antihypertensive therapy. Methods: This multicenter, double-blind, parallel study was conducted in Japan. Adult patients with type 2 diabetes mellitus and uncontrolled nocturnal hypertension receiving stable antihypertensive therapy including angiotensin receptor blockers were randomized to 12 weeks’ treatment with empagliflozin 10 mg once daily or placebo. Clinic BP was measured at baseline and weeks 4, 8, and 12; 24-hour ambulatory BP monitoring was performed at baseline and week 12; and morning home BP was determined for 5 days before each visit. The primary efficacy end point was change from baseline in nighttime BP (ambulatory BP monitoring). Results: One hundred thirty-two nonobese, older patients with well-controlled blood glucose were randomized (mean age 70 years, mean body mass index 26 kg/m 2 ). Empagliflozin, but not placebo, significantly reduced nighttime systolic BP versus baseline (–6.3 mm Hg; P =0.004); between-group difference in change from baseline was –4.3 mm Hg ( P =0.159). Reductions in daytime, 24-hour, morning home, and clinic systolic BP at 12 weeks with empagliflozin were significantly greater than with placebo (–9.5, –7.7, –7.5, and –8.6 mm Hg, respectively; all P ≤0.002). Between-group differences in body weight and glycosylated hemoglobin reductions were significant, but small (–1.3 kg and –0.33%; both P P =0.013); atrial natriuretic peptide levels decreased with empagliflozin versus placebo at weeks 4 and 12 (–8.2% [ P =0.008] and –9.7% [ P =0.019]). Changes in antihypertensive medication during the study did not differ significantly between groups. Conclusions: Nonseverely obese older diabetes patients with uncontrolled nocturnal hypertension showed significant BP reductions without marked reductions in glucose with the addition of empagliflozin to existing antihypertensive and antidiabetic therapy. Use of sodium-glucose cotransporter 2 inhibitors in specific groups (eg, those with nocturnal hypertension, diabetes, and high salt sensitivity) could help reduce the risk of heart failure and cardiovascular mortality. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03050229.

International audience; Background: The PARIS risk score (PARIS-rs) and percutaneous coronary intervention complexity (PCI-c) predict clinical and procedural residual ischemic risk following PCI. Their accuracy in patients undergoing unprotected left main (ULM) or bifurcation PCI has not been assessed.Methods: The predictive performances of the PARIS-rs (categorized as low, intermediate, and high) and PCI-c (according to guideline-endorsed criteria) were evaluated in 3,002 patients undergoing ULM/bifurcation PCI with very thin strut stents.Results: After 16 (12-22) months, increasing PARIS-rs (8.8% vs. 14.1% vs. 27.4%, p < .001) and PCI-c (15.2% vs. 11%, p = .025) were associated with higher rates of major adverse cardiac events ([MACE], a composite of death, myocardial infarction [MI], and target vessel revascularization), driven by MI/death for PARIS-rs and target lesion revascularization/stent thrombosis for PCI-c (area under the curves for MACE: PARIS-rs 0.60 vs. PCI-c 0.52, p-for-difference < .001). PCI-c accuracy for MACE was higher in low-clinical-risk patients; while PARIS-rs was more accurate in low-procedural-risk patients. ≥12-month dual antiplatelet therapy (DAPT) was associated with a lower MACE rate in high PARIS-rs patients, (adjusted-hazard ratio 0.42 [95% CI: 0.22-0.83], p = .012), with no benefit in low to intermediate PARIS-rs patients. No incremental benefit with longer DAPT was observed in complex PCI.Conclusions: In the setting of ULM/bifurcation PCI, the residual ischemic risk is better predicted by a clinical risk estimator than by PCI complexity, which rather appears to reflect stent/procedure-related events. Careful procedural risk estimation is warranted in patients at low clinical risk, where PCI complexity may substantially contribute to the overall residual ischemic risk.

OBJECTIVE Outcomes of complex percutaneous coronary interventions (PCIs) in older patients are still debated. The aim of the study was to evaluate clinical outcomes of Octogenarian patients treated with ultrathinstents on left main or on coronary bifurcations, compared with younger patients. METHODS All consecutive patients presenting a critical lesion of an unprotected left main (ULM) or a bifurcation and treated with very thin stents were included in the RAIN (veRy thin stents for patients with left mAIn or bifurcatioN in real life) registry and divided into octogenarians group (OG, 551 patients) and nonoctogenarians (NOGs, 2,453 patients). Major adverse cardiovascular event (MACE), a composite end point of all-cause death, nonfatal myocardial infarction (MI), target lesion revascularization (TLR), and stent thrombosis (ST), was the primary endpoint, while MACE components, cardiovascular (CV) death, and target vessel revascularization (TVR) were the secondary ones. RESULTS Indication for PCI was acute coronary syndrome in 64.7% of the OG versus 53.1% of the NOG. Severe calcifications and a diffuse disease were significantly more in OG. After a follow-up of 15.2 ± 10.3 months, MACEs were higher in the OG than in the NOG patients (OG 19.1% vs. NOG 11.2%, p

Background The clinical impact of stent strut thickness in coronary bifurcation lesions in small vessels has not been assessed in a real-world population. Methods and results All 506 patients enrolled in the RAIN study, undergoing PCI in a vessel with a diameter 2.5 mm or less were retrospectively evaluated and divided into two groups according to stent strut thickness: 74 μm (n = 206) versus 81 μm (n = 300); 87.1% of the lesions involved bifurcations. TLF [defined as a composite of myocardial infarction (MI) and target lesion revascularization (TLR)] was the primary endpoint, with MACE (a composite of death, MI and TLR), its components and stent thrombosis the secondary endpoint. After 16 (14-18) months, a lower incidence of TLF (4.3 vs. 9.8%, P = 0.026) and ST (1.0 vs. 3.0%, P = 0.042) was seen in the 74 μm group, whereas MACE occurred in 60 of 506 patients, with no statistical difference between the two groups (9.7 vs. 13.3%, P = 0.070). At multivariate analysis, chronic renal failure increased the risk of TLF while thinner strut was an independent protective factor (hazard ratio 0.51, CI 0.17-0.85, P = 0.005). Conclusion In this real-world population, patients being treated for small vessels lesions with thinner strut stents had lower rates of TLF, MI and ST.

BackgroundAtherosclerosis is a chronic inflammatory disease driven by macrophage accumulation in medium and large sized arteries. Macrophage polarization and inflammation are governed by microRNAs (miR) that regulate the expression of inflammatory proteins and cholesterol trafficking. Previous transcriptomic analysis led us to hypothesize that miR-155-5p (miR-155) is regulated by conjugated linoleic acid (CLA), a pro-resolving mediator which induces regression of atherosclerosis in vivo. In parallel, as extracellular vesicles (EVs) and their miR content have potential as biomarkers, we investigated alterations in urinary-derived EVs (uEVs) during the progression of human coronary artery disease (CAD).MethodsmiR-155 expression was quantified in aortae from ApoE−/− mice fed a 1% cholesterol diet supplemented with CLA blend (80:20, cis-9,trans-11:trans-10,cis-12 respectively) which had been previously been shown to induce atherosclerosis regression. In parallel, human polarized THP-1 macrophages were used to investigate the effects of CLA blend on miR-155 expression. A miR-155 mimic was used to investigate its inflammatory effects on macrophages and on ex vivo human carotid endarterectomy (CEA) plaque specimens (n = 5). Surface marker expression and miR content were analyzed in urinary extracellular vesicles (uEVs) obtained from patients diagnosed with unstable (n = 12) and stable (n = 12) CAD.ResultsHere, we report that the 1% cholesterol diet increased miR-155 expression while CLA blend supplementation decreased miR-155 expression in the aorta during atherosclerosis regression in vivo. CLA blend also decreased miR-155 expression in vitro in human THP-1 polarized macrophages. Furthermore, in THP-1 macrophages, miR-155 mimic decreased the anti-inflammatory signaling proteins, BCL-6 and phosphorylated-STAT-3. In addition, miR-155 mimic downregulated BCL-6 in CEA plaque specimens. uEVs from patients with unstable CAD had increased expression of miR-155 in comparison to patients with stable CAD. While the overall concentration of uEVs was decreased in patients with unstable CAD, levels of CD45+ uEVs were increased. Additionally, patients with unstable CAD had increased CD11b+ uEVs and decreased CD16+ uEVs.ConclusionmiR-155 suppresses anti-inflammatory signaling in macrophages, is decreased during regression of atherosclerosis in vivo and is increased in uEVs from patients with unstable CAD suggesting miR-155 has potential as a prognostic indicator and a therapeutic target.

Background: There are limited data regarding the impact of final kissing balloon (FKI) in patients treated with percutaneous coronary intervention using ultrathin stents in left main or bifurcations. Methods: All patients undergoing left main or bifurcations percutaneous coronary intervention enrolled in the RAIN registry (Very Thin Stents for Patients With MAIN or BiF in Real Life: The RAIN, a Multicenter Study) evaluating ultrathin stents were included. Major adverse cardiac event (a composite of all-cause death, myocardial infarction, target lesion revascularization, and stent thrombosis) was the primary end point, while its components, along with target vessel revascularization, were the secondary end points. The main analysis was performed comparing patients with and without FKI after adjustment with inverse probability of treatment weighting. Subgroup analyses were performed according to FKI (short [ Results: Two thousand seven hundred forty-two patients were included. At 16 months (8–20) follow-up, inverse probability of treatment weighting adjusted rates of major adverse cardiac event were similar between FKI and no-FKI group (15.1% versus 15.5%; P =0.967), this result did not change with use of imaging, proximal optimization technique, or routine versus bail-out FKI. In the 2-stent subgroup, FKI was associated with lower rates of target vessel revascularization (7.8% versus 15.9%; P =0.030) and target lesion revascularization (7.3% versus 15.2%; P =0.032). Short overlap FKI was associated with a lower rate of target lesion revascularization compared with no FKI (2.6% versus 5.4%; P =0.034), while long overlap was not (6.8% versus 5.4%; P =0.567). Conclusions: In patients with bifurcations or unprotected left main treated with ultrathin stents, short overlap FKI is associated with less restenosis. In a 2-stent strategy, FKI was associated with less target vessel revascularization and restenosis. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03544294.

Incidence and predictors of adverse events after dual antiplatelet therapy (DAPT) cessation in patients treated with thin stents (

Background There are limited data regarding the impact of bioresorbable polymer drug eluting stent (BP-DES) compared to durable polymer drug eluting stent (DP-DES) in patients treated with percutaneous coronary intervention using ultrathin stents in left main or bifurcations. Methods In the RAIN registry (ClinicalTrials NCT03544294, june 2018 retrospectively registered) patients with a ULM or bifurcation stenosis treated with PCI using ultrathin stents (struts thinner than 81 μm) were enrolled. The primary endpoint was the rate of target lesion revascularization (TLR); major adverse cardiovascular events (MACE, a composite of all-cause death, myocardial infarction, TLR and stent thrombosis) and its components, along with target vessel revascularization (TVR) were the secondary ones. A propensity score with matching analysis to compare patients treated with BP-DES versus DP-DES was also assessed. Results From 3001 enrolled patients, after propensity score analysis 1400 patients (700 for each group) were selected. Among them, 352 had ULM disease and 1048 had non-LM bifurcations. At 16 months (12–22), rates of TLR (3.7% vs 2.9%, p = 0.22) and MACE were similar (12.3% vs. 11.6%, p = 0.74) as well as for the other endpoints. Sensitivity analysis of outcomes after a two-stents strategy, showed better outcome in term of MACE (20.4% vs 10%, p = 0.03) and TVR (12% vs 4.6%, p = 0.05) and a trend towards lower TLR in patients treated with BP-DES. Conclusion In patients with bifurcations or ULM treated with ultrathin stents BP-DES seems to perform similarly to DP-DES: the trends toward improved clinical outcomes in patients treated with the BP-DES might potentially be of value for speculating the stent choice in selected high-risk subgroups of patients at increased risk of ischemic events. Trial registration ClinicalTrials.gov Identifier: NCT03544294. Retrospectively registered June 1, 2018.

International audience; Objectives: To evaluate the independent clinical impact of stent structural features in a large cohort of patients undergoing unprotected left main (ULM) or coronary bifurcation percutaneous coronary intervention (PCI) with a range of very thin strut stents.Background: Clinical impact of structural features of contemporary stents remains to be defined.Methods: All consecutive patients enrolled in the veRy thin stents for patients with left mAIn or bifurcatioN in real life (RAIN) registry were included. The following stent structural features were studied: antiproliferative drugs (everolimus vs. sirolimus vs. zotarolimus), strut material (platinum-chromium vs. cobalt-chromium), polymer (bioresorbable vs. durable), number of crowns (

A significant paravalvular leak (PVL) is estimated in at least 1–3% of patients undergoing surgical aortic and/or mitral valve replacement. Surgical repair of a PVL is associated with a 30-day mortality of approximately 10%. Percutaneous closure of PVL has emerged as an alternative to surgical repair. We sought to examine the clinical outcomes of patients treated with percutaneous closure of PVL at an Irish tertiary referral centre. A prospective registry was used to record patient and procedural characteristics at the time of the PVL procedure. Medical records were retrospectively reviewed to assess clinical outcomes during the index hospitalisation and at follow-up. A total of 26 PVL procedures were performed in 21 patients (mean age 68 ± 13 years, 76% male). Heart failure (HF), haemolysis (HL) or a combination of both was the presenting symptoms in 62%, 24% and 14% of patients, respectively. In the entire cohort, clinical success was achieved in 18 patients (86%). Clinical success was achieved more frequently when HF was the clinical indication compared to HL (100% versus 66%). Among patients presenting with isolated HF (n = 13), the mean NYHA class at baseline and follow-up was 2.5± 0.7 and 1.4± 0.7, respectively. Thirty-day mortality was 0%. There was one (3.8%) major adverse procedural complication (stroke). A total of six deaths (28%) occurred during follow-up (22 ± 13.4 months). Patients with PVL represent a high-risk patient cohort. Percutaneous PVL offers a safe alternative to surgical PVL repair and appears particularly effective in those patients who present primarily with HF.

INTRODUCTION AND OBJECTIVES The predictive value of the SYNTAX score (SS) for clinical outcomes after transcatheter aortic valve implantation (TAVI) is very limited and could potentially be improved by the combination of anatomic and clinical variables, the SS-II. We aimed to evaluate the value of the SS-II in predicting outcomes in patients undergoing TAVI. METHODS A total of 402 patients with severe symptomatic aortic stenosis undergoing transfemoral TAVI were included. Preprocedural TAVI angiograms were reviewed and the SS-I and SS-II were calculated using the SS algorithms. Patients were stratified in 3 groups according to SS-II tertiles. The coprimary endpoints were all-cause death and major adverse cardiovascular events (MACE), a composite of all-cause death, cerebrovascular event, or myocardial infarction at 1 year. RESULTS Increased SS-II was associated with higher 30-day mortality (P=.036) and major bleeding (P=.015). The 1-year risk of death and MACE was higher among patients in the 3rd SS-II tertile (HR, 2.60; P=.002 and HR, 2.66; P

Resumen Introduccion y objetivos La puntuacion SYNTAX (PS) tiene muy escaso valor predictivo de eventos clinicos tras el implante percutaneo de valvula aortica (TAVI), pero que podria mejorar con la combinacion de variables clinicas y anatomicas, la nueva PS-II. Nuestro objetivo es evaluar el valor de la PS-II en la prediccion de eventos en pacientes sometidos a TAVI. Metodos Se incluyo en total a 402 pacientes con estenosis aortica grave sometidos a TAVI. Se reviso la angiografia coronaria antes del procedimiento y se calcularon la PS-I y la PS-II segun los algoritmos de la PS. Se estratifico a los pacientes en 3 grupos en funcion de los terciles de la PS-II. Los objetivos primarios fueron muerte por cualquier causa y los eventos adversos cardiovascular mayores (MACE), un compuesto de muerte, evento cerebrovascular o infarto de miocardio al ano de seguimiento. Resultados Una PS-II aumentada se asocio con mas mortalidad (p = 0,036) y hemorragias mayores (p = 0,015) a los 30 dias. Los riesgos de muerte (HR = 2,60; p = 0,002) y MACE (HR = 2,66; p Conclusiones La PS-II parece mas adecuada que la PS-I para predecir eventos clinicos en pacientes sometidos a TAVI. Una mayor PS-II se asocio a mas eventos clinicos al ano y a los 4 anos de la TAVI, independientemente de la presencia de enfermedad coronaria.

Background: The functional SYNTAX score (FSS) has been shown to improve the discrimination for major adverse cardiac events compared with the anatomic SYNTAX score (SS) while reducing interobserver variability. However, evidence supporting the noninvasive FSS in patients with multivessel coronary artery disease (CAD) is scarce. Objectives: The purpose of this study was to assess the feasibility of and validate the noninvasive FSS derived from coronary computed tomography angiography (CTA) with fractional flow reserve (FFR CT) in patients with 3-vessel CAD. Methods: The CTA-SS was calculated in patients with 3-vessel CAD included in the SYNTAX II (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery II) study. The noninvasive FSS was determined by including only ischemia-producing lesions (FFR CT ≤0.80). SS derived from different imaging modalities were compared using the Bland-Altman and Passing-Bablok method, and the agreement on the SS tertiles was investigated with Cohen's Kappa. The risk reclassification was compared between the noninvasive and invasive physiological assessment, and the diagnostic accuracy of FFR CT was assessed by the area under the receiver-operating characteristic curve using instantaneous wave-free ratio as a reference. Results: The CTA-SS was feasible in 86% of patients (66 of 77), whereas the noninvasive FSS was feasible in 80% (53 of 66). The anatomic SS was overestimated by CTA compared with conventional angiography (27.6 ± 6.4 vs. 25.3 ± 6.9; p < 0.0001) whereas the calculation of the FSS yielded similar results between the noninvasive and invasive imaging modalities (21.6 ± 7.8 vs. 21.2 ± 8.8; p = 0.589). The noninvasive FSS reclassified 30% of patients from the high- and intermediate-SS tertiles to the low-risk tertile, whereas invasive FSS reclassified 23% of patients from the high- and intermediate-SS tertiles to the low-risk tertile. The agreement on the classic SS tertiles based on Kappa statistics was slight for the anatomic SS (Kappa = 0.19) and fair for the FSS (Kappa = 0.32). The diagnostic accuracy of FFR CT to detect functional significant stenosis based on an instantaneous wave-free ratio ≤0.89 revealed an area under the receiver-operating characteristics curve of 0.85 (95% CI: 0.79 to 0.90) with a sensitivity of 95% (95% CI: 89% to 98%), specificity of 61% (95% CI: 48% to 73%), positive predictive value of 81% (95% CI: 76% to 86%), and negative predictive value of 87% (95% CI: 74% to 94%). Conclusions: Calculation of the noninvasive FSS is feasible and yielded similar results to those obtained with invasive pressure-wire assessment. The agreement on the SYNTAX score tertile classification improved with the inclusion of the functional component from slight to fair agreement. FFR CT has good accuracy in detecting functionally significant lesions in patients with 3-vessel CAD. (A Trial to Evaluate a New Strategy in the Functional Assessment of 3-Vessel Disease Using SYNTAX II Score in Patients Treated With PCI; NCT02015832)

Balancing ischaemic and bleeding risks in high-risk populations undergoing percutaneous coronary interventions has become an everyday dilemma for clinicians. It is particularly difficult to make decisions concerning combinations and duration of antiplatelet regimens in women given the poor representation of women in trials that have shaped current practice. Several contemporary landmark trials have recently been presented at the American College of Cardiology. The trials included the Harmonising Optimal Strategy for Treatment of coronary artery diseases-EXtended Antiplatelet Monotherapy, Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention and the TicAgrelor versus CLOpidogrel in Stabilised Patients With Acute Myocardial Infarction. In this article, we summarise the main findings of these trials and include the The Polymer-free Drug-Coated Coronary Stents in Patients at High Bleeding Risk (LEADERS FREE) in search for evidence based best practices for women patients. Although some of these trials had prespecified a subanalysis of sex differences, women constituted only 17%–30% of participants making sex-specific analyses challenging. Data suggest that women benefit from de-escalation to both ticagrelor and clopidogrel monotherapy. However, given the increased bleeding risks observed in women further randomised controlled trials are necessary to determine the most appropriate combination and duration of dual antiplatelet therapy as well as maintenance single antiplatelet therapy.

The noninferiority design is used extensively in current clinical research, but its complex features may hamper the appropriate interpretation of such trials. Thus, understanding the pillars of noninferiority design is indispensable. The authors discuss fundamental concepts regarding the design and interpretation of noninferiority trials and then explore some common methodological criticism by analyzing a sample of contemporary coronary stent trials. Finally, the authors give an overall perspective to enhance the design and conduct of future trials.

AIM To investigate the rates and determinants of success of repeat percutaneous coronary intervention (PCI) following an initial failed attempt at recanalising the chronic total occlusions (CTO) percutaneously. METHODS In 445 consecutive first attempt CTO-PCI procedures in our institution, procedural failure occurred in 149 (33.5%). Sixty-four re-PCI procedures were performed in 58 patients (39%) all had a single CTO. Procedural and outcome data in the re-PCI population was entered into the institutional database. A retrospective analysis of clinical, angiographic and procedural data was performed. RESULTS Procedural success was achieved in 41 (64%) procedures. Univariate analysis of clinical and angiographic characteristics showed that re-PCI success was associated with intravascular ultrasound (IVUS) guidance (19.5% vs 0%, P = 0.042), while failure was associated with severe calcification (30.4% vs 9.7%, P = 0.047) and a JCTO score > 3 (56.5% vs 17.1% P = 0.003). Following multiple regression analysis the degree of lesion complexity (J-CTO score > 3), IVUS use, involvement of an experienced CTO operator and LAD CTO location were significant predictors of successful re-PCI. Overall the complication rate was low, with the only MACCE two periprocedural MI’s neither of which required intervention. CONCLUSION Re-PCI substantially increases the overall success rate of CTO revascularization. Predictors of re-PCI success included the use of IVUS, the involvement of an experienced CTO operator in the repeat attempt and the location of the CTO.

Inability to cross the lesion with a guidewire is the most common reason for failure in percutaneous revascularization (PCI) of chronic total occlusions (CTOs). An ostial or stumpless CTO is an acknowledged challenge for CTO recanalization due to difficulty in successful wiring. IVUS imaging provides the opportunity to visualize the occluded vessel and to aid guidewire advancement. We review the value of this technique in a single-centre experience of CTO PCI. This series involves 22 patients who underwent CTO-PCI using IVUS guidance for stumpless CTO wiring at our institution. CTO operators with extensive IVUS experience in non-CTO cases carried out all procedures. Procedural and outcome data was prospectively entered into the institutional database and a retrospective analysis of clinical, angiographic and technical data performed. 17 (77%) of the 22 procedures were successful. The mean age was 59.8 ± 11.5 years, and 90.9% were male. The most commonly attempted lesions were located in the left anterior descending 36.4% (Soon et al. in J Intervent Cardiol 20(5):359-366, 2007) and Circumflex artery (LCx) 31.8% (Mollet et al. in Am J Cardiol 95(2):240-243, 2005). Mean JCTO score was 3.09 ± 0.75 (3.06 ± 0.68, 3.17 ± 0.98 in the successful and failed groups respectively p = 0.35). The mean contrast volume was 378.7 ml ± 114.7 (389.9 ml ± 130.5, 349.2 ml ± 52.2 p = 0.3 in the successful and failed groups respectively). There was no death, coronary artery bypass grafting or myocardial infarction requiring intervention in this series. When the success rates were analyzed taking into account the date of adoption of this technique, the learning curve had no significant impact on CTO-PCI success. This series describes a good success rate in IVUS guided stumpless wiring of CTOs in consecutive patients with this complex anatomical scenario.

Item does not contain fulltext The coronary microcirculation plays a key role in modulating blood supply to the myocardium. Several factors like myocardial oxygen demands, endothelial and neurogenic conditions determine its function. Although there is available evidence supporting microvascular dysfunction as an important cause of myocardial ischaemia, with both prognostic and symptomatic implications, its diagnosis and management in clinical practice is still relegated to a second plane. Both diagnostic and therapeutic approaches are hampered by the broadness of the concept of microvascular dysfunction, which fails addressing the plurality of mechanisms leading to dysfunction. Normal microcirculatory function requires both structural integrity of the microcirculatory vascular network and preserved signalling pathways ensuring adequate and brisk arteriolar resistance shifts in response to myocardial oxygen demands. Pathological mechanisms affecting these requirements include structural remodelling of microvessels, intraluminal plugging, extravascular compression or vasomotor dysregulation. Importantly, not every diagnostic technique provides evidence on which of these pathophysiological mechanisms is present or predominates in the microcirculation. In this paper we discuss the mechanisms of coronary microvascular dysfunction and the intracoronary tools currently available to detect it, as well as the potential role of each one to unmask the main underlying mechanism.

Background People with cerebral palsy (CP) may be at increased risk of musculoskeletal conditions due to various factors including malnutrition and abnormal levels of skeletal loading. This study aimed to compare the incidence of osteoporosis, osteoarthritis and inflammatory musculoskeletal diseases between adults with and without CP. Methods A population based cohort study was conducted using data from the Clinical Practice Research Datalink collected between 1987 and 2015. Adults with CP were matched to adults without CP for age, sex and general practice. Cox models, stratified by matched set and adjusted for potential confounders, were fitted to compare the risk of osteoporosis, osteoarthritis and inflammatory musculoskeletal diseases. Results 1705 adults with CP were matched to 5115 adults without CP. Adults with CP had an increased risk of osteoporosis in unadjusted (Hazard Ratio (HR) 3.67, 95% Confidence Interval (CI) 2.32 to 5.80, p ˂ 0.001) and adjusted (HR 6.19, 95% CI 3.37 to 11.39, p ˂ 0.001) analyses. No evidence of increased risk of inflammatory musculoskeletal diseases was observed in unadjusted or adjusted analyses. For osteoarthritis no evidence of increased risk was seen in the unadjusted analysis, but evidence of an increased risk was seen when the analysis was adjusted for alcohol consumption, smoking status, and mean yearly general practice (GP) visits (HR 1.54, 95% CI 1.17 to 2.02, p ˂ 0.001). Conclusions After accounting for potential confounding variables, we found that CP is associated with increased risk of osteoporosis and osteoarthritis. These findings provide the strongest epidemiological evidence to date for increased risk of osteoporosis and osteoarthritis in people with CP, and highlight need for clinical awareness of such conditions in this population.

ObjectiveTo compare the incidence of noncommunicable diseases between adults with and without cerebral palsy (CP).MethodsA cohort study was conducted using primary care data from the Clinical Practice Research Datalink. Cox models, stratified by matched set and adjusted for potential confounders, were fitted to compare the risk of any noncommunicable disease, cancer, cardiovascular disease, type 2 diabetes mellitus, and respiratory disease between adults with and without CP.ResultsThe analysis included 1,705 adults with CP and 5,115 age-, sex-, and general practice–matched adults without CP. There was evidence from adjusted analyses that adults with CP had 75% increased risk of developing any noncommunicable disease compared to adults without CP (hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.58–1.94). Specifically, they had increased risk of cardiovascular disease (HR 1.76, 95% CI 1.48–2.11) and respiratory disease (HR 2.61, 95% CI 2.14–3.19). There was no evidence of increased risk of cancer or type 2 diabetes mellitus.ConclusionsAdults with CP had increased risk of noncommunicable disease, specifically cardiovascular and respiratory disease. These findings highlight the need for clinical vigilance regarding identification of noncommunicable disease in people with CP and further research into the etiology and management of noncommunicable disease in this population.

AIMS To establish the value of the SYNTAX Score-II (SS-II) in predicting long-term mortality of patients treated with left main PCI (LM-PCI) using second-generation drug-eluting stents (DES). METHODS AND RESULTS The SYNTAX score (SS) and the SS-II were calculated in 804 patients included in the FAILS-2 registry (failure in left main study with 2nd generation stents). Patients were classified in low (SS-II ≤33; n = 278, 34.6%), intermediate (SS-II 34-43; n = 260, 32.3%) and high (SS-II ≥44; n = 266, 33.1%) SS-II tertiles. Primary endpoint was all-cause mortality. A significant difference in long-term mortality was noted (5.2 ± 3.6 years): 4.1, 7.5, and 16.7% in low, mid and high SS-II tertiles respectively (p

Introduction Percutaneous coronary intervention (PCI) for complex lesions, including unprotected left main (ULM) and bifurcations, is gaining a relevant role in treating coronary artery disease with good outcomes, also thanks to new generation stents. The daily risk of adverse cardiovascular events and their temporal distribution after these procedures is not known. Methods All consecutive patients presenting with a critical lesion of ULM or bifurcation treated with very thin struts stents, enrolled in the RAIN-Cardiogroup VII study, were analyzed. The daily risk of major acute cardiovascular events (MACE), target lesion revascularization (TLR) and stent thrombosis (ST) and their temporal distribution in the first year of follow-up was the primary endpoint. Differences among subgroups (ULM, patient presentation, kind of stent polymer) were the secondary endpoint. Results 2745 patients were included, mean age 68 ± 11 years, 33.3% diabetics, 54.5% had an acute coronary syndrome (ACS); 88.5% of treated lesions were bifurcations, 27.2% ULM. Average daily risk was 0.022% for MACE, 0.005% for TLR and 0.004% for ST, in the first year. Bimodal distribution of adverse events, especially TLR, with an early peak in the first 50 days and a late one after 150 days, was observed. Patients with ULM presented a significantly higher daily risk of events, and ACS patients presented higher MACE risk. No difference emerged according to the type of stent polymer. Conclusions The daily risk of adverse events in the first year after complex PCI in our study is acceptably low. PCI on ULM carries a higher risk of complications.

Few data are available about the impact on outcomes of procedural strategies for percutaneous coronary intervention with thin-struts stents on unprotected left main (ULM): 792 patients with an ULM stenosis treated with percutaneous coronary intervention with thin-strut stents were enrolled in the present multicenter registry. Target lesion revascularization (TLR) was the primary end point. MACE (a composite of all-cause death, myocardial infarction, TLR, and stent thrombosis) and its single components, along with target vessel revascularization were the secondary end points. Subgroup analyses were performed according to complex versus noncomplex bifurcation lesions. After 16 months, 5.5% of patients experienced a TLR. At multivariate analysis, provisional stenting (odds ratio [OR] 0.46: 0.85 to 0.23, p = 0.006), use of imaging (OR 0.45: 0.23 to 0.98, p = 0.003) and final kissing balloon (FKB) (OR 0.41: 0.83 to 0.21, p = 0.001) reduced risk of TLR. FKB reduced risk of overall TLR only for 2 stents-strategy (6.2% vs 32.4%, p

Intravascular ultrasound imaging has contributed to circumvent some limitations of coronary angiography by providing information on the characteristics of the arterial wall and facilitating accurate measurements of luminal dimensions. In addition to providing valuable in vivo observations on the natural history of coronary artery disease, it has contributed significantly to the assessment of interventional devices and drugs addressing coronary artery disease. For the interventional cardiologist it constitutes a valuable tool that allows planning and optimization of percutaneous interventions, with growing information supporting the hypothesis that its use translates into better patient outcomes.

Background Covered stent (CS) implantation is considered a useful device in the setting of Grade III Coronary Perforation (G3CP), one of the most harmful PCI complication. However, data regarding efficacy of this device and clinical outcomes are still limited. Methods and results From 1993 to 2015, among 97,779 patients from 9 European centres undergoing PCI, 224 patients had G3CP (0.23%), and 102 patients were managed with CS implantation (96 with PTFE, 6 with pericardium). Device oriented composite endpoint (DOCE), a composite of cardiac death, target lesion revascularization, and stent thrombosis (ST) in-hospital and at long term follow-up were evaluated. G3-CP perforations were successfully sealed with CS in 88 patients (86.3%) with need of intraprocedural pericardiocentesis in one-third of cases. Protamine as heparin reversal agent was administered in 36 (35%) of cases. The cumulative incidence of in-hospital DOCE were 16.6% (17/102): death 14.7%, TLR 2.9%, ST 3.9%. At long-term follow-up (mean 42 ± 38 months), DOCE rates occurred in 19.7%: death 7.4%, TLR 11%, and ST 6.2%. Indication to Dual Antiplatelet Therapy (DAPT) was lifelong in 20% of cases, 1 to 6 months in 22.5% and 12-months in 57.5% without differences in long-term DOCE before and after DAPT interruption (8.0 vs. 6.6%, respectively, P = 0.20). Conclusions Use of CS was successful in sealing grade 3 coronary artery perforations in the majority of cases. Beside the high rate of clinical events at short and long-term, ST remains the leading cause of device failure.

OBJECTIVES The aim of this study was to investigate the clinical outcomes of patients deferred from coronary revascularization on the basis of instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) measurements in stable angina pectoris (SAP) and acute coronary syndromes (ACS). BACKGROUND Assessment of coronary stenosis severity with pressure guidewires is recommended to determine the need for myocardial revascularization. METHODS The safety of deferral of coronary revascularization in the pooled per-protocol population (n = 4,486) of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) and iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome) randomized clinical trials was investigated. Patients were stratified according to revascularization decision making on the basis of iFR or FFR and to clinical presentation (SAP or ACS). The primary endpoint was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year. RESULTS Coronary revascularization was deferred in 2,130 patients. Deferral was performed in 1,117 patients (50%) in the iFR group and 1,013 patients (45%) in the FFR group (p amp;lt; 0.01). At 1 year, the MACE rate in the deferred population was similar between the iFR and FFR groups (4.12% vs. 4.05%; fully adjusted hazard ratio: 1.13; 95% confidence interval: 0.72 to 1.79; p = 0.60). A clinical presentation with ACS was associated with a higher MACE rate compared with SAP in deferred patients (5.91% vs. 3.64% in ACS and SAP, respectively; fully adjusted hazard ratio: 0.61 in favor of SAP; 95% confidence interval: 0.38 to 0.99; p = 0.04). CONCLUSIONS Overall, deferral of revascularization is equally safe with both iFR and FFR, with a low MACE rate of about 4%. Lesions were more frequently deferred when iFR was used to assess physiological significance. In deferred patients presenting with ACS, the event rate was significantly increased compared with SAP at 1 year. (C) 2018 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. Funding Agencies|Philips; Upsala Clinical Research Centre; Volcano; Imperial College; Philips Volcano; Imperial College London; Medical Research Council

The prevalence of heart failure depends on the definition used, but it is estimated that it affects approximately 1% to 2% of the general population and approximately 10% of those >70 years of age, with coronary artery disease being the most common etiology [(1)][1]. Chronic total occlusions (CTO)

Background In diabetic patients a predisposed coronary microcirculation along with a higher risk of distal particulate embolization during primary percutaneous intervention (PCI) increases the risk of peri-procedural microcirculatory damage. However, new antiplatelet agents, in particular Ticagrelor, may protect the microcirculation through its adenosine-mediated vasodilatory effects. Methods PREDICT is an original, prospective, randomized, multicenter controlled study designed to investigate the protective effect of Ticagrelor on the microcirculation during PCI in patient with diabetes mellitus type 2 or pre-diabetic status. The primary endpoints of this study aim to test (i) the decrease in microcirculatory resistance with antiplatelet therapy (Ticagrelor > Clopidogrel; mechanistic effect) and (ii) the relative microcirculatory protection of Ticagrelor compared to Clopidogrel during PCI (Ticagrelor Conclusions PREDICT will be the first multicentre clinical trial to test the adenosine-mediated vasodilatory effect of Ticagrelor on the microcirculation during PCI in diabetic patients. The results will provide important insights into the prospective beneficial effect of this drug in preventing microvascular impairment related to PCI (http://www.clinicaltrials.gov No. NCT02698618).

The coronary microvasculature is an extremely dynamic system that responds to multiple physiological conditions in order to maintain adequate myocardial perfusion [1, 2]. Modulation of microcirculatory resistance plays a key role in this regulatory process. The underling pathophysiology and adaptive mechanisms of the microcirculation are fully described in other chapters in this book. In patients with ischemic heart disease (IHD), obstructive lesions in epicardial vessels are not a prerequisite for myocardial ischemia [3], which may arise from microcirculatory dysfunction (MCD). It has been shown that MCD is an independent predictor of poorer clinical outcomes in different clinical scenarios [4, 5] and, therefore, outlining its presence in such clinical situations might be important.

Acute coronary syndromes constitute one of the most serious presentations of ischemic heart disease, accounting for a significant proportion of patients investigated and treated in the catheterization laboratory. When assessing both coronary stenoses and the microcirculation in the context of acute coronary syndromes (ACS), it is important to bear in mind that both ST elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTE-ACS) are associated with distinct modifications in coronary physiology and that therefore the principles applied to their assessment in chronic stable angina may not hold true. In this chapter we discuss the pathophysiology of the microvasculature during ACS followed by a review of the benefits and limitations of physiological assessment of both epicardial stenosis and the microvasculature during ACS.

Contains fulltext : 182263.pdf (Publisher’s version ) (Open Access) Aims: To 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 results: The 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). Conclusion: At 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 Identifier: NCT02015832.

While fractional flow reserve has greatly contributed to the clinical applicability of ischemia-driven revascularization, it cannot provide information on whether other realms of the coronary circulation, which also cause myocardial ischemia, such as the microvasculature, are affected. A growing body of evidence suggests that the combined use of coronary flow reserve and fractional flow reserve can provide a much richer view of the status the coronary circulation. Such multimodal physiological assessment of the coronary circulation can be further enriched with the incorporation of measurements of resistance derived from thermodilution or Doppler flow velocity and intracoronary pressure. In this chapter we review the rationale for and available evidence on multimodal coronary physiology, providing examples of its applicability in the clinical field.

Background Buried bumper syndrome (BBS) is an uncommon but significant complication of percutaneous endoscopic gastrostomy (PEG), which occurs due to overgrowth of gastric mucosa over the inner bumper of the gastrostomy tube. A high incidence of BBS was observed in patients with Freka PEG tubes. Objective To review case numbers of BBS and confirm the observed association with Freka tubes to determine whether change of practice should be considered. Design Data was collected on the number of cases of BBS reported to the community nutrition team Birmingham, UK. Data on type of PEG kit and total number of PEGs inserted between 2009 and 2013 were collected. The electronic endoscopy reporting database was used to compare case numbers of BBS in our Trust in years when Corflo and Freka PEG tubes were used, respectively. Data from our Trust were also compared with that from a Trust using Corflo only. Results Fifty-eight cases of BBS were reported in the area covered by the Birmingham community nutrition team between 2009 and 2013, all of which were associated with Freka PEG tubes. An estimated 1000–1200 PEGs were inserted during this period, representing an incidence of BBS of 4.8–5.8%. No cases of BBS occurred over the same period in the comparison Trust (451 Corflo PEGs inserted). Conclusions Our review confirmed our observation of an increased risk of BBS with Freka PEG tubes. Clinicians should be aware of our findings when deciding which brand of PEG tube to insert, particularly in patients with a previous history of BBS.

Aim Calcineurin inhibitors are substrates for P-glycoprotein (P-gp), the expression of which is associated with ABCB1 C3435T polymorphism. Individual P-gp response to calcineurin inhibitor may be linked to nephrotoxicity or rejection. 99mTc-2-Methoxyisobutylisonitrile (99mTc-MIBI) is also a P-gp substrate. The aim of this study, therefore, was to determine 99mTc-MIBI organ kinetics and compare them with ABCB1 genotype with a view to replacing 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) with 99mTc-MIBI in renal transplant care. Methods Thirty prospective donors (13 male) were imaged for 20 min after administration of 99mTc-MIBI (400 MBq) intravenously. Posterior images of the abdomen were acquired at 30 and 120 min. Organ 30 min/peak count rate ratios and exponential two-point (30–120 min) rate constants (k, min−1) were calculated. Nineteen donors were genotyped for C3435T (exon 26), G2677T (exon 21), C1236T (exon 12), and G1199A (exon 11) ABCB1 polymorphisms using a PCR-based technique. Results 99mTc-MIBI and 99mTc-MAG3 gave similar perfusion images. Although their patterns of renal elimination were different, differential renal function was not significantly different. There was a negative trend between the hepatic 30 min/peak ratio and C3435T genotype (CC: 0.8374±0.0502; TC: 0.6806±0.1300; TT: 0.6919±0.1506; P=0.083). Renal k showed a negative trend with C3435T (CC: 0.0021±0.0020; TC: 0.0037±0.0013; TT: 0.0040±0.0012 min−1; P=0.087) but with no other genotypes. There were no significant sex-related differences in 99mTc-MIBI kinetics. Conclusion 99mTc-MIBI can replace 99mTc-MAG3 for pretransplant workup. The ABCB1 C3435T polymorphism may influence 99mTc-MIBI kinetics and thus have a role in renal transplant care. Further prospective trials are required to establish the full potential of 99mTc-MIBI in renal transplant management.

Objective: Technetium-99m-labelled hexakis-methoxy-isobutyl isonitrile (Tc-99m-MIBI) is a substrate for P-glycoprotein (P-gp), an ATP-binding cassette (ABC) transporter protein, and can be used to image P-gp expression. The aim was to study normal kinetics of Tc-99m-MIBI in the kidney and liver to help understand physiological studies of P-gp expression in these organs. Methods: Thirty healthy kidney transplant donors received intravenous Tc-99m-MIBI followed by dynamic scintigraphy for 20 min and static imaging at 30 and 120 min. Time-activity curves were generated from parenchymal ROI. An assumed mono-exponential Tc-99m-MIBI blood clearance with rate constant of 0.3 min-1 was used to predict the Tc-99m- MIBI that would have accumulated in the organs had none left. The activities leaving were then calculated by subtraction and expressed as percentages of the predicted total accumulated activities. Results: Kidney time-activity curves peaked at 2-4 min then declined to a plateau from ~15-16 min equal to 31 [SD 5]% of the total activity accumulated (corresponding to 69 [5]% rapidly eliminated) (phase 1). Bladder activity followed a similar but opposite time course. Between 30 and 120 min (phase 2), activity left at 0.36 (0.13) %.min-1. Liver curves peaked at 8-10 min. Differentiation of the elimination curve revealed that a variable proportion of tracer (5-56%; mean 30 [14]%) was rapidly excreted over ~11 min. From 30 min, activity left at 1.02 (0.23) %.min-1. There was no correlation between renal and hepatic elimination rates in either phase or between early and late phase elimination rates in either organ. Conclusions: Early renal elimination is predominantly via glomerular filtration and urinary excretion. The liver rapidly excretes a more variable and lower proportion of Tc-99m-MIBI than the kidney. P-gp located at the urine/tubule and bile/hepatocyte boundaries prevents Tc-99m-MIBI re-entering cells and thereby influences elimination and retention in both phases, although other ABC transporters are probably also involved.

Aims The applicability of the results of the SYNTAX trial comparing percutaneous coronary intervention (PCI) using first-generation drug-eluting stents (DES) with coronary artery bypass graft (CABG) surgery for the treatment of patients with complex coronary artery disease (CAD) has been challenged by recent major technical and procedural developments in coronary revascularisation. Functional assessment of coronary lesions has contributed to marked improvements in both safety and efficacy of DES implantation. In addition, the recent development of the SYNTAX score II, a clinical tool based on anatomical and clinical factors, allows individualised objective decision making regarding the optimal revascularisation modality in patients with complex CAD. The ongoing SYNTAX II trial is currently evaluating the effectiveness of the clinical and technological advances in the treatment of patients with complex (de novo three-vessel) CAD. Methods and results The SYNTAX II trial is a multicentre, all-comers, open-label, single-arm trial aiming to recruit 450 patients with de novo three-vessel CAD in approximately 25 European interventional cardiology centres. All patients will be selected and treated following the SYNTAX II strategy, which includes: a) establishing the appropriateness of revascularisation utilising the SYNTAX score II as a clinical tool to allow objective decision making by the Heart Team, b) ischaemia-driven revascularisation based on functional intracoronary assessment, c) implantation of the new-generation everolimus-eluting platinum chromium coronary stent with thin struts and abluminal bioabsorbable polymer coating to promote rapid vessel healing, d) intravascular ultrasound-guided DES implantation, and e) treatment at centres with expertise in CTO recanalisation. The primary endpoint is a composite of the major adverse cardiac and cerebral events (MACCE) rate at one-year follow-up compared to the historical PCI arm of the SYNTAX trial. An exploratory endpoint will be MACCE at five-year follow-up compared to the historical surgical arm of the SYNTAX trial. Conclusions The SYNTAX II trial will provide valuable information on outcomes of state-of-the-art PCI for the contemporary management of complex (de novo three-vessel) CAD. SYNTAX II will be of critical value in the design of future trials in this arena.

Background Serotonin (5-HT) induces platelet aggregation by activating its 5-HT 2A receptor. Platelet uptake is mediated by the 5-HT transporter (5-HTT). A common 5-HTT promoter (5-HTTLPR) splice variant results in long (L) and short (S) alleles. 5-HTTLPR genotype has been associated with increased platelet activation and risk of MI. Variation within HTR2A gene (C1354T) that encodes the 5-HT 2A receptor has also been associated with enhanced platelet aggregation. We hypothesised that 5-HTT and/or HTR2A variation may influence platelet response to aspirin in patients with stable CAD. Methods Patients ( n = 144) with stable cardiovascular disease taking aspirin were genotyped for the 5-HTTLPR and HTR2A variants. Platelet inhibition was assessed by serum thromboxane and arachidonic acid-induced platelet aggregation assay. Results 5-HTT genotype (LL vs *S) was a significant determinant of serum TX level (8.9 ± 2.6 ng/ml vs 6.0 ± 1.6 ng/ml respectively; p 2 > 2.2 ng/ml) ( p = 0.04; OR = 2.22, CI = 1.03–4.79). Odds ratio of the effect of LL genotype on TX elevation was 3.8 (95% CI 1.2–11.6) in younger patients (under 64) compared to 1.0 (95% CI = 0.3–3.8) in older subjects. LL genotype did not influence AA aggregation ( p = 0.83, OR = 1.2, CI = 0.3–4.1). The HTR2A variant had no effect on TX generation ( p = 0.70; OR = 1.22, CI = 0.45–3.26) nor AA aggregation ( p = 0.99; OR = 1.0, CI = 0.2–4.9). Conclusions In younger patients with stable CAD 5HTT LL genotype carried by almost one third of our cohort is associated with a diminished response to aspirin that may increase cardiovascular risk. Genotypic variation in platelet activation may be a contributing mechanism.

QFR, an angiographic index of stenosis severity based on computational fluid dynamics, estimates fractional flow reserve (FFR) without coronary instrumentation. Although QFR incorporates TIMI frame count as a surrogate of flow, it is unknown whether QFR is influenced by microvascular dysfunction. We