Inorganic nitrate benefits contrast-induced nephropathy after coronary angiography for acute coronary syndromes: the NITRATE-CIN trial.

BACKGROUND AND AIMS: Contrast-induced nephropathy (CIN), also known as contrast-associated acute kidney injury (CA-AKI) underlies a significant proportion of the morbidity and mortality following coronary angiographic procedures in high-risk patients and remains a significant unmet need. In pre-clinical studies inorganic nitrate, which is chemically reduced in vivo to nitric oxide, is renoprotective but this observation is yet to be translated clinically. In this study, the efficacy of inorganic nitrate in the prevention of CIN in high-risk patients presenting with acute coronary syndromes (ACS) is reported. METHODS: NITRATE-CIN is a double-blind, randomized, single-centre, placebo-controlled trial assessing efficacy of inorganic nitrate in CIN prevention in at-risk patients presenting with ACS. Patients were randomized 1:1 to once daily potassium nitrate (12 mmol) or placebo (potassium chloride) capsules for 5 days. The primary endpoint was CIN (KDIGO criteria). Secondary outcomes included kidney function [estimated glomerular filtration rate (eGFR)] at 3 months, rates of procedural myocardial infarction, and major adverse cardiac events (MACE) at 12 months. This study is registered with ClinicalTrials.gov: NCT03627130. RESULTS: Over 3 years, 640 patients were randomized with a median follow-up of 1.0 years, 319 received inorganic nitrate with 321 received placebo. The mean age of trial participants was 71.0 years, with 73.3% male and 75.2% Caucasian; 45.9% had diabetes, 56.0% had chronic kidney disease (eGFR <60 mL/min) and the mean Mehran score of the population was 10. Inorganic nitrate treatment significantly reduced CIN rates (9.1%) vs. placebo (30.5%, P < .001). This difference persisted after adjustment for baseline creatinine and diabetes status (odds ratio 0.21, 95% confidence interval 0.13-0.34). Secondary outcomes were improved with inorganic nitrate, with lower rates of procedural myocardial infarction (2.7% vs. 12.5%, P = .003), improved 3-month renal function (between-group change in eGFR 5.17, 95% CI 2.94-7.39) and reduced 1-year MACE (9.1% vs. 18.1%, P = .001) vs. placebo. CONCLUSIONS: In patients at risk of renal injury undergoing coronary angiography for ACS, a short (5 day) course of once-daily inorganic nitrate reduced CIN, improved kidney outcomes at 3 months, and MACE events at 1 year compared to placebo.

Non-ST-elevation acute coronary syndromes with previous coronary artery bypass grafting: a meta-analysis of invasive vs. conservative management.

BACKGROUND AND AIMS: A routine invasive strategy is recommended in the management of higher risk patients with non-ST-elevation acute coronary syndromes (NSTE-ACSs). However, patients with previous coronary artery bypass graft (CABG) surgery were excluded from key trials that informed these guidelines. Thus, the benefit of a routine invasive strategy is less certain in this specific subgroup. METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted. A comprehensive search was performed of PubMed, EMBASE, Cochrane, and ClinicalTrials.gov. Eligible studies were RCTs of routine invasive vs. a conservative or selective invasive strategy in patients presenting with NSTE-ACS that included patients with previous CABG. Summary data were collected from the authors of each trial if not previously published. Outcomes assessed were all-cause mortality, cardiac mortality, myocardial infarction, and cardiac-related hospitalization. Using a random-effects model, risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. RESULTS: Summary data were obtained from 11 RCTs, including previously unpublished subgroup outcomes of nine trials, comprising 897 patients with previous CABG (477 routine invasive, 420 conservative/selective invasive) followed up for a weighted mean of 2.0 (range 0.5-10) years. A routine invasive strategy did not reduce all-cause mortality (RR 1.12, 95% CI 0.97-1.29), cardiac mortality (RR 1.05, 95% CI 0.70-1.58), myocardial infarction (RR 0.90, 95% CI 0.65-1.23), or cardiac-related hospitalization (RR 1.05, 95% CI 0.78-1.40). CONCLUSIONS: This is the first meta-analysis assessing the effect of a routine invasive strategy in patients with prior CABG who present with NSTE-ACS. The results confirm the under-representation of this patient group in RCTs of invasive management in NSTE-ACS and suggest that there is no benefit to a routine invasive strategy compared to a conservative approach with regard to major adverse cardiac events. These findings should be validated in an adequately powered RCT.

Computed Tomography Cardiac Angiography Before Invasive Coronary Angiography in Patients With Previous Bypass Surgery: The BYPASS-CTCA Trial.

BACKGROUND: Patients with previous coronary artery bypass grafting often require invasive coronary angiography (ICA). However, for these patients, the procedure is technically more challenging and has a higher risk of complications. Observational studies suggest that computed tomography cardiac angiography (CTCA) may facilitate ICA in this group, but this has not been tested in a randomized controlled trial. METHODS: This study was a single-center, open-label randomized controlled trial assessing the benefit of adjunctive CTCA in patients with previous coronary artery bypass grafting referred for ICA. Patients were randomized 1:1 to undergo CTCA before ICA or ICA alone. The co-primary end points were procedural duration of the ICA (defined as the interval between local anesthesia administration for obtaining vascular access and removal of the last catheter), patient satisfaction after ICA using a validated questionnaire, and the incidence of contrast-induced nephropathy. Linear regression was used for procedural duration and patient satisfaction score; contrast-induced nephropathy was analyzed using logistic regression. We applied the Bonferroni correction, with P<0.017 considered significant and 98.33% CIs presented. Secondary end points included incidence of procedural complications and 1-year major adverse cardiac events. RESULTS: Over 3 years, 688 patients were randomized with a median follow-up of 1.0 years. The mean age was 69.8±10.4 years, 108 (15.7%) were women, 402 (58.4%) were White, and there was a high burden of comorbidity (85.3% hypertension and 53.8% diabetes). The median time from coronary artery bypass grafting to angiography was 12.0 years, and there were a median of 3 (interquartile range, 2 to 3) grafts per participant. Procedure duration of the ICA was significantly shorter in the CTCA+ICA group (CTCA+ICA, 18.6±9.5 minutes versus ICA alone, 39.5±16.9 minutes [98.33% CI, -23.5 to -18.4]; P<0.001), alongside improved mean ICA satisfaction scores (1=very good to 5=very poor; -1.1 difference [98.33% CI, -1.2 to -0.9]; P<0.001), and reduced incidence of contrast-induced nephropathy (3.4% versus 27.9%; odds ratio, 0.09 [98.33% CI, 0.04-0.2]; P<0.001). Procedural complications (2.3% versus 10.8%; odds ratio, 0.2 [95% CI, 0.1-0.4]; P<0.001) and 1-year major adverse cardiac events (16.0% versus 29.4%; hazard ratio, 0.4 [95% CI, 0.3-0.6]; P<0.001) were also lower in the CTCA+ICA group. CONCLUSIONS: For patients with previous coronary artery bypass grafting, CTCA before ICA leads to reductions in procedure time and contrast-induced nephropathy, with improved patient satisfaction. CTCA before ICA should be considered in this group of patients. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03736018.

REGENERATE-COBRA: A phase II randomized sham-controlled trial assessing the safety and efficacy of intracoronary administration of autologous bone marrow-derived cells in patients with refractory angina.

AIMS: The REGENERATE-COBRA trial (NCT05711849) will assess the safety and efficacy of an intracoronary infusion of autologous bone marrow-derived mononuclear cells in refractory angina patients with no revascularization options who are symptomatic despite optimal medical and device therapy. METHODS: REGENERATE-COBRA is a single site, blinded, randomized, sham-controlled, Phase II clinical trial enrolling 110 refractory angina patients with no revascularization options who are symptomatic despite optimal medical and device therapy. Patients will be randomized to either autologous bone marrow derived-mononuclear cells or a sham procedure. Patients in the cell-treated arm will undergo a bone marrow aspiration and an intracoronary infusion of autologous bone marrow derived-mononuclear cells. Patients in the control arm will undergo a sham bone marrow aspiration and a sham intracoronary infusion. The trial's primary endpoint is an improvement in Canadian Cardiovascular Society (CCS) angina class by 2 classes between baseline and 6 months. Secondary endpoints include change in: CCS class at 12 months, myocardial ischemic burden (as measured by perfusion imaging) at 6 months, quality of life at 6 and 12 months (as measured by EQ-5D-5L, EQ-5D-VAS and Seattle Angina Questionnaire), angina frequency at 6 and 12 months, total exercise time (as measured by a modified Bruce protocol) and major adverse cardiovascular events at 6 and 12 months. CONCLUSIONS: This is the first trial to assess the safety and efficacy of an intracoronary infusion of autologous bone marrow-derived unfractionated mononuclear cells in symptomatic refractory angina patients who have exhausted conventional therapeutic options.

Iatrogenic catheter-induced ostial coronary artery dissections: Prevalence, management, and mortality from a cohort of 55,968 patients over 10 years.

OBJECTIVE: We sought to describe the prevalence, management strategies and evaluate the prognosis of patients with iatrogenic catheter-induced ostial coronary artery dissection (ICOCAD). BACKGROUND: ICOCAD is a rare but potentially devastating complication of cardiac catheterisation. The clinical manifestations of ICOCAD vary from asymptomatic angiographic findings to abrupt vessel closure leading to myocardial infarction and death. METHODS: 55,968 patients who underwent coronary angiography over a 10-year period were screened for ICOCAD as defined by the National Heart, Lung, and Blood Institute. The management and all-cause mortality were retrieved from local and national databases. RESULTS: The overall prevalence of ICOCAD was 0.09% (51/55,968 patients). Guide catheters accounted for 75% (n = 37) of cases. Half of the ICOCAD cases involved the right coronary artery while the remaining were related to left main stem (23/51; 45%) and left internal mammary artery (2/51; 4%). Two-thirds of ICOCAD were high grade (type D, E, and F). The majority of cases were type F dissections (n = 18; 66%), of which two third occurred in females in their 60s. The majority of ICOCAD patients (42/51; 82%) were treated with percutaneous coronary intervention while the remaining underwent coronary artery bypass grafting (3/51; 6%) or managed conservatively (6/51; 12%). Three deaths occurred during the index admission while 48/51 patients (94.1%) were safely discharged without further mortality over a median follow-up of 3.6 years. CONCLUSIONS: ICOCAD is a rare but life-threatening complication of coronary angiography. Timely recognition and prompt bailout PCI is a safe option for majority of patients with good clinical outcomes.

The Impact of Cell Therapy on Cardiovascular Outcomes in Patients With Refractory Angina.

RATIONALE: Cell-based therapies are a novel potential treatment for refractory angina and have been found to improve markers of angina. However, the effects on mortality and major adverse cardiac events (MACE) have not been definitively investigated. OBJECTIVE: To investigate the efficacy and safety of stem cell treatment compared with optimal medical treatment for refractory angina by conducting an updated meta-analysis, looking at clinical outcomes. METHODS AND RESULTS: We performed a systematic review and meta-analysis of randomized controlled trials using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A comprehensive search was performed of PubMed, EMBASE (Excerpta Medica database), Cochrane, ClinicalTrials.gov , Google Scholar databases of randomized controlled trials, and scientific session abstracts. Studies were deemed eligible if they met the following criteria: (1) full-length publications in peer-reviewed journals; (2) evaluated cell therapy use in patients with no further revascularisation options while on optimal medical treatment; (3) patients had ongoing angina, Canadian Cardiovascular Society class II-IV; and (4) included a placebo/control arm. We calculated risk ratios for all-cause mortality, combined MACE events. We assessed heterogeneity using χ2 and I2 tests. We identified 1191 citations with 8 randomized controlled trials meeting inclusion criteria involving 526 patients. Outcomes pooled were MACE, mortality, and indices of angina (angina episodes, Canadian Cardiovascular Society angina class, exercise tolerance, and antianginal medications). Our analysis showed a decreased risk of both MACE (odds ratio, 0.41; CI, 0.25-0.70) and mortality (odds ratio, 0.24; 95% CI, 0.10-0.60) in cell-treated patients compared with patients on maximal medical therapy. This was supported by improvements in surrogate end points of anginal episodes, use of antianginal medications, Canadian Cardiovascular Society class, and exercise tolerance. CONCLUSIONS: In addition to improvements in indices of angina, cell-based therapies improve cardiovascular outcomes (mortality/MACE) in patients with refractory angina. Given the premature termination of the phase III study, this supports the need for further definitive trials. Prospero Registration : URL: https://www.crd.york.ac.uk/prospero/ . Unique identifier: CRD42018084257.

Use of quantitative cardiovascular magnetic resonance myocardial perfusion mapping for characterization of ischemia in patients with left internal mammary coronary artery bypass grafts.

BACKGROUND: Quantitative myocardial perfusion mapping using cardiovascular magnetic resonance (CMR) is validated for myocardial blood flow (MBF) estimation in native vessel coronary artery disease (CAD). Following coronary artery bypass graft (CABG) surgery, perfusion defects are often detected in territories supplied by the left internal mammary artery (LIMA) graft, but their interpretation and subsequent clinical management is variable. METHODS: We assessed myocardial perfusion using quantitative CMR perfusion mapping in 38 patients with prior CABG surgery, all with angiographically-proven patent LIMA grafts to the left anterior descending coronary artery (LAD) and no prior infarction in the LAD territory. Factors potentially determining MBF in the LIMA-LAD myocardial territory, including the impact of delayed contrast arrival through the LIMA graft were evaluated. RESULTS: Perfusion defects were reported on blinded visual analysis in the LIMA-LAD territory in 27 (71%) cases, despite LIMA graft patency and no LAD infarction. Native LAD chronic total occlusion (CTO) was a strong independent predictor of stress MBF (B = - 0.41, p = 0.014) and myocardial perfusion reserve (MPR) (B = - 0.56, p = 0.005), and was associated with reduced stress MBF in the basal (1.47 vs 2.07 ml/g/min; p = 0.002) but not the apical myocardial segments (1.52 vs 1.87 ml/g/min; p = 0.057). Extending the maximum arterial time delay incorporated in the quantitative perfusion algorithm, resulted only in a small increase (3.4%) of estimated stress MBF. CONCLUSIONS: Perfusion defects are frequently detected in LIMA-LAD subtended territories post CABG despite LIMA patency. Although delayed contrast arrival through LIMA grafts causes a small underestimation of MBF, perfusion defects are likely to reflect true reductions in myocardial blood flow, largely due to proximal native LAD disease.

The association between the public reporting of individual operator outcomes with patient profiles, procedural management, and mortality after percutaneous coronary intervention: an observational study from the Pan-London PCI (BCIS) Registry using an interrupted time series analysis.

AIMS: The public reporting of healthcare outcomes has a number of potential benefits; however, unintended consequences may limit its effectiveness as a quality improvement process. We aimed to assess whether the introduction of individual operator specific outcome reporting after percutaneous coronary intervention (PCI) in the UK was associated with a change in patient risk factor profiles, procedural management, or 30-day mortality outcomes in a large cohort of consecutive patients. METHODS AND RESULTS: This was an observational cohort study of 123 780 consecutive PCI procedures from the Pan-London (UK) PCI registry, from January 2005 to December 2015. Outcomes were compared pre- (2005-11) and post- (2011-15) public reporting including the use of an interrupted time series analysis. Patients treated after public reporting was introduced were older and had more complex medical problems. Despite this, reported in-hospital major adverse cardiovascular and cerebrovascular events rates were significantly lower after the introduction of public reporting (2.3 vs. 2.7%, P < 0.0001). Interrupted time series analysis demonstrated evidence of a reduction in 30-day mortality rates after the introduction of public reporting, which was over and above the existing trend in mortality before the introduction of public outcome reporting (35% decrease relative risk 0.64, 95% confidence interval 0.55-0.77; P < 0.0001). CONCLUSION: The introduction of public reporting has been associated with an improvement in outcomes after PCI in this data set, without evidence of risk-averse behaviour. However, the lower reported complication rates might suggest a change in operator behaviour and decision-making confirming the need for continued surveillance of the impact of public reporting on outcomes and operator behaviour.

Reliable in vivo intravascular imaging plaque characterization: A challenge unmet.

Intravascular imaging has enabled in vivo assessment of coronary artery pathology and detection of plaque characteristics that are associated with increased vulnerability. Prospective invasive imaging studies of coronary atherosclerosis have demonstrated that invasive imaging modalities can detect lesions that are likely to progress and cause cardiovascular events and provided unique insights about atherosclerotic evolution. However, despite the undoubted value of the existing imaging techniques in clinical and research arenas, all the available modalities have significant limitations in assessing plaque characteristics when compared with histology. Hybrid/multimodality intravascular imaging appears able to overcome some of the limitations of standalone imaging; however, there are only few histology studies that examined their performance in evaluating plaque pathobiology. In this article, we review the evidence about the efficacy of standalone and multi-modality/hybrid intravascular imaging in assessing plaque morphology against histology, highlight the advantages and limitations of the existing imaging techniques and discuss the future potential of emerging imaging modalities in the study of atherosclerosis.

Umbilical cord-derived mesenchymal stromal cells in cardiovascular disease: review of preclinical and clinical data.

The human umbilical cord has recently emerged as an attractive potential source of mesenchymal stromal cells (MSCs) to be adopted for use in regenerative medicine. Umbilical cord MSCs (UC-MSCs) not only share the same features of all MSCs such as multi-lineage differentiation, paracrine functions and immunomodulatory properties, they also have additional advantages, such as no need for bone marrow aspiration and higher self-renewal capacities. They can be isolated from various compartments of the umbilical cord (UC) and can be used for autologous or allogeneic purposes. In the past decade, they have been adopted in cardiovascular disease and have shown promising results mainly due to their pro-angiogenic and anti-inflammatory properties. This review offers an overview of the biological properties of UC-MSCs describing available pre-clinical and clinical data with respect to their potential therapeutic use in cardiovascular regeneration, with current challenges and future directions discussed.

Transient rise in His-lead threshold due to acute myocardial infarction.

An 85-year-old male was admitted to our center with a non-ST elevation myocardial infarction. The patient had a dual-chamber pacemaker in situ with an atrial and His lead. A transient increase in His threshold and loss of nonselective capture occurred at the presentation of right coronary artery infarction, peaking during rotational atherectomy therapy causing loss of capture and complete atrioventricular block. A follow-up interrogation, 2 weeks postrevascularization, showed a return to a normal nonselective capture morphology and threshold measurements. Physicians should be aware of this complication in patients with His leads, particularly those with a history of coronary artery disease.

Routine use of fluoroscopic guidance and up-front femoral angiography results in reduced femoral complications in patients undergoing coronary angiographic procedures: an observational study using an Interrupted Time-Series analysis.

Transradial access is increasingly used for coronary angiography and percutaneous coronary intervention, however, femoral access remains necessary for numerous procedures, including complex high-risk interventions, structural procedures, and procedures involving mechanical circulatory support. Optimising the safety of this approach is crucial to minimize costly and potentially life-threatening complications. We initiated a quality improvement project recommending routine fluoroscopic guidance (femoral head), and upfront femoral angiography should be performed to assess for location and immediate complications. We assessed the effect of these measures on the rate of vascular complications. Data were collected prospectively on 4534 consecutive patients undergoing femoral coronary angiographic procedures from 2015 to 2017. The primary end-point was any access complication. Outcomes were compared pre and post introduction including the use of an Interrupted Time-Series (ITS) analysis. 1890 patients underwent angiography prior to the introduction of routine fluoroscopy and upfront femoral angiography and 2644 post. All operators adopted these approaches. Baseline characteristics, including large sheath use, anticoagulant use and PCI rates were similar between the 2 groups. Fluoroscopy-enabled punctures were made in the 'safe zone' in over 91% of cases and upfront femoral angiography resulted in management changes i.e. procedural abandonment prior to heparin administration in 21 patients (1.1%). ITS analysis demonstrated evidence of a reduction in femoral complication rates after the introduction of the intervention, which was over and above the existing trend before the introduction (40% decrease RR 0.58; 95% CI: 0.25-0.87; P < 0.01). Overall these quality improvement measures were associated with a significantly lower incidence of access site complications (0.9% vs. 2.0%, P < 0.001). Routine fluoroscopy guided vascular access and upfront femoral angiography prior to anticoagulation leads to lower vascular complication rates. Thus, study shows that femoral intervention can be performed safely with very low access-related complication rates when fluoroscopic guidance and upfront angiography is used to obtain femoral arterial access.

Primary Management of Squamous Cell Carcinoma of the Anal Canal: A 30-year Community Hospital Experience.

We reviewed outcomes of 41 patients treated with curative-intent radiotherapy for anal canal carcinoma at a community hospital between 1985 and 2015. Twenty-six (63%) presented with stage I or II disease while 15 (37%) had stage III. Thirty-seven received definitive chemoradiation and 4 radiotherapy alone. Thirteen (31.7%) received ≤59.4Gy. Thirty-two (78%) were treated with 3-dimensional conformal radiotherapy while 9 (22%) received intensity-modulated radiotherapy. At 5 years, local control, regional control, freedom from distant metastasis, cause-specific survival, and overall survival were 80%, 98%, 88%, 77%, and 51%. Of those who received >59.4Gy, local control and overall survival were not improved.

Randomized phase 2 trial of intracoronary nitrite during acute myocardial infarction.

RATIONALE: Preclinical evidence demonstrates that inorganic nitrite, after its in situ conversion to nitric oxide, attenuates consequent myocardial reperfusion injury. OBJECTIVE: We investigated whether intracoronary injection of nitrite during primary percutaneous coronary intervention might improve infarct size in ST-elevated myocardial infarction. METHODS AND RESULTS: Patients undergoing primary percutaneous coronary intervention (n=80) were randomized to receive intracoronary (10 mL) sodium nitrite (1.8 µmol) or NaCl (placebo) before balloon inflation. The primary end point was infarct size assessed by measuring creatine kinase release. Secondary outcomes included infarct size assessed by troponin T release and by cardiac MRI on day 2. Baseline characteristics were similar between the groups. No evidence of differences in creatine kinase release (P=0.92), troponin T (P=0.85), or cardiac MRI-assessed infarct size (P=0.254) were evident. In contrast, there was an improvement [corrected] in myocardial salvage index (P=0.05) and reduction in [corrected] major adverse cardiac event at 1 year (2.6% versus 15.8%; P=0.04) in the nitrite group. In a 66-patient subgroup with thrombolysis in myocardial infarction ≤1 flow, there was reduced serum creatine kinase (P=0.030) and a 19% reduction in cardiac MRI-determined infarct size (P=0.034) with nitrite. No adverse effects of nitrite were detected. CONCLUSIONS: In this phase II study, intracoronary nitrite infusion did not alter infarct size, although a trend to improved myocardial salvage index and a significant reduction in major adverse cardiac event was evident. In a subgroup of patients with thrombolysis in myocardial infarction flow ≤1, nitrite reduced infarct size and major adverse cardiac event and improved myocardial salvage index, indicating that a phase III clinical trial assessing intracoronary nitrite administration as an adjunct to percutaneous coronary intervention in ST-elevated myocardial infarction patients is warranted. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01584453.

Cardiovascular magnetic resonance imaging of myocardial oedema following acute myocardial infarction: Is whole heart coverage necessary?

BACKGROUND: AAR measurement is useful when assessing the efficacy of reperfusion therapy and novel cardioprotective agents after myocardial infarction. Multi-slice (Typically 10-12) T2-STIR has been used widely for its measurement, typically with a short axis stack (SAX) covering the entire left ventricle, which can result in long acquisition times and multiple breath holds. This study sought to compare 3-slice T2-short-tau inversion recovery (T2- STIR) technique against conventional multi-slice T2-STIR technique for the assessment of area at risk (AAR). METHODS: CMR imaging was performed on 167 patients after successful primary percutaneous coronary intervention. 82 patients underwent a novel 3-slice SAX protocol and 85 patients underwent standard 10-slice SAX protocol. AAR was obtained by manual endocardial and epicardial contour mapping followed by a semi- automated selection of normal myocardium; the volume was expressed as mass (%) by two independent observers. RESULTS: 85 patients underwent both 10-slice and 3-slice imaging assessment showing a significant and strong correlation (intraclass correlation coefficient = 0.92;p < 0.0001) and a low Bland-Altman limit (mean difference -0.03 ± 3.21%, 95% limit of agreement,- 6.3 to 6.3) between the 2 analysis techniques. A further 82 patients underwent 3-slice imaging alone, both the 3-slice and the 10-slice techniques showed statistically significant correlations with angiographic risk scores (3-slice to BARI r = 0.36, 3-slice to APPROACH r = 0.42, 10-slice to BARI r = 0.27, 10-slice to APPROACH r = 0.46). There was low inter-observer variability demonstrated in the 3-slice technique, which was comparable to the 10-slice method (z = 1.035, p = 0.15). Acquisition and analysis times were quicker in the 3-slice compared to the 10-slice method (3-slice median time: 100 seconds (IQR: 65-171 s) vs. (10-slice time: 355 seconds (IQR: 275-603 s); p < 0.0001. CONCLUSIONS: AAR measured using 3-slice T2-STIR technique correlates well with standard 10-slice techniques, with no significant bias demonstrated in assessing the AAR. The 3-slice technique requires less time to perform and analyse and is therefore advantageous for both patients and clinicians.

Does Modified Footwear Improve Gait After Ankle Arthrodesis?

Rocker bottom shoes are commonly recommended for patients who have undergone ankle arthrodesis. Limited data are available to support this recommendation. In the present case-control study, 2 groups of participants were identified for the investigation: a study group (SG) of 9 patients who had previously undergone ankle arthrodesis and a normal group (NG) of 9 healthy volunteers. Gait data were collected using a video recorder while the participants walked barefoot and wearing rocker bottom shoes. These data were analyzed using computer-based gait analysis software. The total motion was calculated and averaged for each group for walking barefoot and wearing rocker bottom shoes. All participants completed the Short Musculoskeletal Function Assessment and the American Orthopaedic Foot and Ankle Society questionnaires. The total motion of the SG wearing rocker bottom shoes increased 4.8° (range 3.4° to 6.9°) on mean average, an improvement compared with walking barefoot (p < .05). In the NG, the shoe wear had no effect on the total motion (p = .59). Although the total motion in the SG approached the mean average of the total motion of the NG, it remained significantly less than that of the NG (p < .05). Additionally, the SG scored worse than the NG on both outcomes questionnaires (p < .05). Rocker bottom shoes had no effect on gait velocity. In conclusion, rocker bottom shoes significantly improve the total motion of ankle arthrodesis patients toward normal.

Clinical outcomes after myocardial revascularization according to operator training status: cohort study of 22,697 patients undergoing percutaneous coronary intervention or coronary artery bypass graft surgery.

AIMS: Myocardial revascularization by either coronary artery bypass graft surgery (CABG) or percutaneous coronary intervention (PCI) carries the risk of serious complications. Observational data suggest that outcomes may be improved by experienced operators, but there are few studies that have analysed the relationship between mortality and primary operator grade. The aim of this study was to investigate the effect of operator grade (trainee vs. consultant) upon outcomes of revascularization procedures. METHODS AND RESULTS: This was an observational study at a tertiary cardiology centre with accredited training programmes, between 2003 and 2011. A total of 22 697 consecutive patients undergoing either CABG or PCI were included. Associations between operator grade and mortality were assessed by hazard ratios, estimated by Cox regression analyses; 6689 patients underwent CABG, whereas 16 008 underwent PCI. Trainees performed 1968 (29.4%) CABG procedures and 8502 (53.1%) PCI procedures. The proportion of procedures performed by trainees declined over time for both CABG (30.2% in 2003 vs. 26.0% in 2010) and for PCI (58.1% in 2003 vs. 44.5% in 2010). In the unadjusted Cox analysis, consultant operator grade was associated with an increased 5-year mortality after both CABG [HR: 1.26 (95% CI: 1.07-1.47)] and PCI procedures [HR: 1.34 (95% CI: 1.22-1.47)] compared with a trainee operator. However, following multiple adjustment, consultant grade was no longer associated with mortality after either procedure [CABG: HR: 1.02 (95% CI: 0.87-1.20), PCI: HR: 1.08 (95% CI: 0.98-1.20)]. CONCLUSION: There was no observed detrimental effect on patient outcomes arising from procedures undertaken by trainees working in a structured training environment compared with consultants.

Dapagliflozin in Myocardial Infarction without Diabetes or Heart Failure.

BACKGROUND: In patients with acute myocardial infarction (MI), therapies that could further reduce the risk of adverse cardiovascular and metabolic outcomes are needed. METHODS: In this international registry-based, randomized, double-blind trial, patients without prior diabetes or chronic heart failure, presenting with acute MI and impaired left ventricular systolic function, were randomly assigned 10 mg of dapagliflozin or placebo, given once daily. The primary outcome was the hierarchical composite of death, hospitalization for heart failure, nonfatal MI, atrial fibrillation/flutter, type 2 diabetes mellitus, New York Heart Association Functional Classification at the last visit, and body weight decrease of 5% or greater at the last visit using the win ratio analysis method. The key secondary outcome was the same hierarchical composite excluding the body weight component. RESULTS: We enrolled 4017 patients of whom 2019 were assigned to dapagliflozin and 1998 to placebo. The analysis of the primary hierarchical composite outcome resulted in significantly more wins for dapagliflozin than for placebo (win ratio, 1.34; 95% confidence interval [CI], 1.20 to 1.50; P<0.001). The win ratio outcome, which was adopted in a change of analysis during trial performance because of low event accrual, was mainly driven by the added cardiometabolic outcomes. The composite of time to cardiovascular death/hospitalization for heart failure occurred in 50/2019 (2.5%) patients assigned to dapagliflozin and 52/1998 (2.6%) patients assigned to placebo (hazard ratio, 0.95; 95% CI, 0.64 to 1.40). The rates of other cardiovascular events were low, with differences between the groups not reaching nominal statistical significance. No safety concerns were identified. CONCLUSIONS: In patients with acute MI as noted above, after approximately 1 year of treatment with dapagliflozin there were significant benefits with regard to improvement in cardiometabolic outcomes but no impact on the composite of cardiovascular death or hospitalization for heart failure compared with placebo. (Funded by AstraZeneca; ClinicalTrial.gov number, NCT04564742.)