Ultra-low contrast, complex left main coronary intervention case series using novel intravascular ultrasound technology.

BACKGROUND: Contrast-induced nephropathy (CIN) in patients with chronic kidney disease (CKD) carries a high morbidity and mortality. Ultra-low contrast percutaneous coronary intervention (ULPCI) has previously been described. Complex left main (LM) ULPCI using two-stent strategy guided by novel intravascular ultrasound (IVUS) co-registration software has not been described. We report a series of complex LM ULPCI using IVUS co-registration. CASE SUMMARIES: Five patients with estimated glomerular filtration rate ≤20 mL/min who presented with stable angina or non-ST segment elevation acute coronary syndrome underwent percutaneous coronary intervention (PCI). The patients previously had diagnostic angiography performed as a separate procedure. Successful LM ULPCI was performed in all patients with a provisional and two-stent bifurcation strategies. These were complex procedures, some of which required haemodynamic support and rotational atherectomy. DISCUSSION: This report describes the first ULPCI using a dedicated two-stent LM bifurcation strategy and using rotational atherectomy and IVUS co-registration. This technology facilitated complex PCI in this high-risk patient group with minimal contrast use (≤6 mL) with optimal results and no patients developed acute kidney injury after intervention. The adaptation of ULPCI to daily practice in patients at risk of CIN will improve treatment for this underserved patient group.

Emergent Percutaneous Rotational Atherectomy to Bailout Surgical Transapical Aortic Valve Implantation: A Successful Case of Heart Team Turnaround / Aterectomia Rotacional Percutânea Emergencial para Dar Suporte ao Implante Cirúrgico Transapical da Válvula Aórtica: Um Caso Bem Sucedido de Reviravolta da Equipe Cardíaca

Abstract Transcatheter aortic valve implantation (TAVI) is an established treatment for severe aortic stenosis (AS) in patients with elevated surgical risk. Concomitant coronary artery disease affects 55-70% of patients with severe AS. Percutaneous coronary intervention in patients with TAVI can be challenging. We report a case of acute coronary obstruction immediately following transapical TAVI deployment requiring emergent rotational atherectomy.

Resumo O implante valvar aórtico transcateter (TAVI) é um tratamento estabelecido para estenose aórtica grave (EA) em pacientes com risco cirúrgico elevado. Doença arterial coronariana concomitante afeta 55-70% dos pacientes com EA grave. A intervenção coronária percutânea em pacientes com TAVI pode ser um desafio. Relatamos um caso de obstrução coronariana aguda imediatamente após o implante de TAVI transapical, exigindo aterectomia rotacional emergencial.

Antithrombotic treatment after coronary artery bypass graft surgery: systematic review and network meta-analysis.

OBJECTIVE: To assess the effects of different oral antithrombotic drugs that prevent saphenous vein graft failure in patients undergoing coronary artery bypass graft surgery. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Medline, Embase, Web of Science, CINAHL, and the Cochrane Library from inception to 25 January 2019. ELIGIBILITY CRITERIA: for selecting studies Randomised controlled trials of participants (aged ≥18) who received oral antithrombotic drugs (antiplatelets or anticoagulants) to prevent saphenous vein graft failure after coronary artery bypass graft surgery. MAIN OUTCOME MEASURES: The primary efficacy endpoint was saphenous vein graft failure and the primary safety endpoint was major bleeding. Secondary endpoints were myocardial infarction and death. RESULTS: This review identified 3266 citations, and 21 articles that related to 20 randomised controlled trials were included in the network meta-analysis. These 20 trials comprised 4803 participants and investigated nine different interventions (eight active and one placebo). Moderate certainty evidence supports the use of dual antiplatelet therapy with either aspirin plus ticagrelor (odds ratio 0.50, 95% confidence interval 0.31 to 0.79, number needed to treat 10) or aspirin plus clopidogrel (0.60, 0.42 to 0.86, 19) to reduce saphenous vein graft failure when compared with aspirin monotherapy. The study found no strong evidence of differences in major bleeding, myocardial infarction, and death among different antithrombotic therapies. The possibility of intransitivity could not be ruled out; however, between-trial heterogeneity and incoherence were low in all included analyses. Sensitivity analysis using per graft data did not change the effect estimates. CONCLUSIONS: The results of this network meta-analysis suggest an important absolute benefit of adding ticagrelor or clopidogrel to aspirin to prevent saphenous vein graft failure after coronary artery bypass graft surgery. Dual antiplatelet therapy after surgery should be tailored to the patient by balancing the safety and efficacy profile of the drug intervention against important patient outcomes. STUDY REGISTRATION: PROSPERO registration number CRD42017065678.

Radial versus femoral approach for left ventricular endomyocardial biopsy.

AIMS: Despite the widespread use of the radial approach in coronary interventions, left ventricular endomyocardial biopsy (LV-EMB) is most frequently performed via the femoral artery. We sought to assess the feasibility and safety of radial compared to femoral access in a large cohort of patients undergoing LV-EMB. METHODS AND RESULTS: Data from 264 patients who underwent LV-EMB in Germany, Portugal, Japan and Canada were collected. Clinical, procedural, safety and feasibility data were evaluated and compared between the two groups. LV-EMB was successfully performed by the radial approach in 129 (99%) of 130 and in 134 (100%) patients by the femoral access. Patients in the radial group were older (mean age 55.7 versus 44.3 years) and were more likely to have moderate-severe mitral regurgitation (27.7% versus TF 0%). Sheathless guides were used in 108 (83.1%) of the radial and 2 (1.5%) of the femoral patients, so the mean guiding catheter size (radial 7.0±1.0 Fr versus femoral 8.0±0.0 Fr) was significantly smaller in the radial group (p<0.001). Mild or moderate radial artery spasm occurred in 13 (10.0%) patients but only one (0.8%) patient required conversion to femoral access due to severe spasm. No access site-related complications were reported in the radial group, while 11 (8.2%) patients in the femoral group had access-site haematomas (p=0.001). There were no major complications (mitral valve injury, pericardial tamponade requiring intervention, cerebrovascular accidents, persistent high-degree atrioventricular block, major bleeding or death) in either group. CONCLUSIONS: The radial approach for LV-EMB appears to be safe and associated with a high success rate while possibly leading to fewer access-site bleeding complications compared to the femoral access. The results of this international multicentre study support the radial approach for LV-EMB and further inspire the expansion of "radial first" in the field of interventional cardiology.

Transradial Approach for Left Ventricular Endomyocardial Biopsy.

BACKGROUND: Left ventricular endomyocardial biopsy (LV-EMB) may offer a superior diagnostic yield compared with right ventricular endomyocardial biopsy (RV-EMB) in conditions predominantly affecting the LV but is underused compared with RV-EMB. Despite the steep uptake of radial approach in coronary interventions, LV-EMB is usually performed via the femoral artery in contemporary practice. Therefore, the aim of this study was to assess the safety and feasibility of LV-EMB via a transradial approach in a multicentre registry. METHODS: One-hundred and two patients who underwent LV-EMB via transradial approach were included. Clinical characteristics, procedural, safety and feasibility data were evaluated. RESULTS: LV-EMB was successfully performed via transradial access in 101 (99%) patients. Mild or moderate radial artery spasm occurred in 12 (12%) patients, but only 1 (0.98%) patient required conversion to femoral access due to severe spasm. A total of 80 (78%) patients had LV-EMB via a sheathless guide catheter. Among those, 77 (96.3%) patients had 7.5-French sheathless guides, and 3 (3.8%) patients had 8.5-French sheathless guides inserted. Radial sheaths were used in the remaining 22 patients, with 5-French sheaths in 21 of 22 patients. Heparin was administered to 93.1% of patients at a median dose of 5000 (3000-5000) IU. The remaining patients followed a provisional strategy upon patent hemostasis achievement. No access site-related complications were reported. There were no major complications (pericardial tamponade, life-threatening arrhythmia, cerebrovascular accident or death). CONCLUSIONS: In a population of patients undergoing transradial LV-EMB, the procedural success rate was high and showed an excellent safety profile. Further studies comparing transradial and transfemoral routes may help expand the use of transradial access for LV-EMB.

Antithrombotic therapy in patients receiving saphenous vein coronary artery bypass grafts: a protocol for a systematic review and network meta-analysis.

INTRODUCTION: The current evidence for the prevention of saphenous vein graft failure (SVGF) after coronary artery bypass graft (CABG) surgery consists of direct head-to-head comparison of treatments (including placebo) in randomised-controlled trials (RCTs) and observational studies. However, summarising the evidence using traditional pairwise meta-analyses does not allow the inclusion of data from treatments that have not been compared head to head. Exclusion of such comparisons could impact the precision of pooled estimates in a meta-analysis. Hence, to address the challenge of whether aspirin alone or in addition to another antithrombotic agent is a more effective regimen to improve SVG patency, a network meta-analysis (NMA) is necessary. The objectives of this study are to synthesise the available evidence on antithrombotic agents (or their combination) and estimate the treatment effects among direct and indirect treatment comparisons on SVGF and major adverse cardiovascular events, and to generate a treatment ranking according to their efficacy and safety outcomes. METHODS: We will perform a systematic review of RCTs evaluating antithrombotic agents in patients undergoing CABG. A comprehensive English literature search will be conducted using electronic databases and grey literature resources to identify published and unpublished articles. Two individuals will independently and in duplicate screen potential studies, assess the eligibility of potential studies and extract data. Risk of bias and quality of evidence will also be evaluated independently and in duplicate. We will investigate the data to ensure its suitability for NMA, including adequacy of the outcome data and transitivity of treatment effects. We plan to estimate the pooled direct, indirect and the mixed effects for all antithrombotic agents using a NMA. ETHICS AND DISSEMINATION: Due to the nature of the study, there are no ethical concerns nor informed consent required. We anticipate that this NMA will be the first to simultaneously assess the relative effects of multiple antithrombotic agents in patients undergoing CABG. The results of this NMA will inform clinicians, patients and guideline developers the best available evidence on comparative effects benefits of antithrombotic agents after CABG while considering the side effect profile to support future clinical decision-making. We will disseminate the results of our systematic review and NMA through a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42017065678.

An exploratory randomized control study of combination cytokine and adult autologous bone marrow progenitor cell administration in patients with ischaemic cardiomyopathy: the REGENERATE-IHD clinical trial.

AIMS: The effect of combined cytokine and cell therapy in ischaemic cardiomyopathy is unknown. Meta-analyses suggest improved cardiac function with cell therapy. The optimal cell delivery route remains unclear. We investigated whether granulocyte colony-stimulating factor (G-CSF) alone or in combination with intracoronary (i.c.) or intramyocardial (i.m.) injection of autologous bone marrow-derived cells (BMCs) improves cardiac function. METHODS AND RESULTS: Ninety patients with symptomatic ischaemic cardiomyopathy and no further treatment options were enrolled in the randomized, placebo-controlled, single-centre REGENERATE-IHD study. Randomization was to one of three arms: peripheral, i.c., or i.m. In each arm, patients were randomized to active treatment or placebo. All patients, apart from the peripheral placebo group (saline only) received G-CSF for 5 days. The i.c. and i.m. arms received either BMCs or serum (placebo). The primary endpoint was change in LVEF at 1 year assessed by cardiac magnetic resonance imaging/computed tomography. The i.m. BMC group showed a significant improvement in LVEF of 4.99% (95% confidence interval 0.33-9.6%; P = 0.038) at 1 year. This group also showed a reduction in NYHA class at 1 year and NT-proBNP at 6 months. No other group showed a significant change in LVEF. This finding is supported by post-hoc between-group comparisons. CONCLUSION: We have shown that G-CSF combined with autologous i.m. BMCs has a beneficial effect on cardiac function and symptoms. However, this result should be considered preliminary in support of a clinical benefit of i.m. stem cell infusion in 'no option' patients and needs further exploration in a larger study.

Randomized trial of combination cytokine and adult autologous bone marrow progenitor cell administration in patients with non-ischaemic dilated cardiomyopathy: the REGENERATE-DCM clinical trial.

AIMS: The REGENERATE-DCM trial is the first phase II randomized, placebo-controlled trial aiming to assess if granulocyte colony-stimulating factor (G-CSF) administration with or without adjunctive intracoronary (IC) delivery of autologous bone marrow-derived cells (BMCs) improves global left ventricular (LV) function in patients with dilated cardiomyopathy (DCM) and significant cardiac dysfunction. METHODS AND RESULTS: Sixty patients with DCM and left ventricular ejection fraction (LVEF) at referral of ≤45%, New York Heart Association (NYHA) classification ≥2 and no secondary cause for the cardiomyopathy were randomized equally into four groups: peripheral placebo (saline), peripheral G-CSF, peripheral G-CSF and IC serum, and peripheral G-CSF and IC BMC. All patients, except the peripheral placebo group, received 5 days of G-CSF. In the IC groups, this was followed by bone marrow harvest and IC infusion of cells or serum on Day 6. The primary endpoint was LVEF change from baseline to 3 months, determined by advanced cardiac imaging. At 3 months, peripheral G-CSF combined with IC BMC therapy was associated with a 5.37% point increase in LVEF (38.30% ± 12.97 from 32.93% ± 16.46 P = 0.0138), which was maintained to 1 year. This was associated with a decrease in NYHA classification, reduced NT-pro BNP, and improved exercise capacity and quality of life. No significant change in LVEF was seen in the remaining treatment groups. CONCLUSION: This is the first randomized, placebo-controlled trial with a novel combination of G-CSF and IC cell therapy that demonstrates an improvement in cardiac function, symptoms, and biochemical parameters in patients with DCM.

Clinical feasibility study to detect angiogenesis following bone marrow stem cell transplantation in chronic ischaemic heart failure.

BACKGROUND: Bone marrow stem cell (BMSC) therapy for cardiovascular disease has shown considerable preclinical and clinical promise, but there remains a need for mechanistic studies to help bridge the transition from bench to bedside. We have designed a substudy to our REGENERATE-IHD trial (ClinicalTrial.gov Identifier: NCT00747708) to assess the feasibility of a novel imaging technique to detect angiogenesis following BMSC therapy. METHODS AND RESULTS: Nine patients who had been randomized to receive intracoronary injection of G-CSF-mobilized BMSCs or control (serum) were included in this substudy. Patients underwent SPECT imaging using a novel radiolabelled peptide (Tc-NC100692), which has a high affinity for the αvß3 integrin, an angiogenesis-related integrin. This was repeated 4 days after intracoronary injection of BMSCs/control to assess for neoangiogenesis. The imaging study was well tolerated with no adverse effects. Myocardial tracer uptake was detectable at baseline in all nine patients, with no myocardial uptake seen in two control patients used for comparison. Baseline uptake appeared to correlate with baseline ejection fraction but changes with therapy did not reach statistical significance. CONCLUSION: SPECT imaging with a Tc-NC100692 is feasible in patients with heart failure, with baseline activity suggesting persistent angiogenesis in patients with remote myocardial infarction.

A randomised double-blind control study of early intracoronary autologous bone marrow cell infusion in acute myocardial infarction (REGENERATE-AMI).

INTRODUCTION: Acute myocardial infarction (AMI) remains a major cause of mortality and morbidity worldwide despite the latest therapeutic advances designed to decrease myocardial injury. Preclinical and emerging clinical evidence show that the intracoronary injection of autologous bone marrow mononuclear cells (BMCs) following AMI leads to improvement in left ventricular ejection function (LVEF). In this clinical trial we will for the first time assess the effect of early (<24 h) infusion of autologous BMCs following AMI on cardiac function. METHODS AND ANALYSIS: REGENERATE-AMI is a double-blind, randomised, multicentre, placebo-controlled trial to determine whether early (<24 h) intracoronary infusion of BMCs improves LVEF after AMI. The study will enrol 100 patients presenting with an anterior AMI demonstrating anterior regional wall motion abnormality. Patients will be randomised to receive intracoronary infusion of BMCs or placebo (0.9% saline). Primary endpoint will be change in LVEF at 1 year compared to baseline, measured by cardiac MRI. Secondary endpoints at 6 months include the change in global LVEF relative to baseline measured by quantitative left ventriculography and echocardiography, as well as major adverse cardiac events which is also measured at 1 year. ETHICS AND DISSEMINATION: The study will be performed in agreement with the Declaration of Helsinki and is approved by local ethics committee (NRES Committee London West London: 07/Q0603/76). TRIAL REGISTRATION: http://clincialtrials.gov (NCT00765453). The results of the trial will be published according to the CONSORT statement and will be presented at conferences and reported in peer-reviewed journals.