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.

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.

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.

Evaluation of the Efficacy of Computed Tomographic Coronary Angiography in Assessing Coronary Artery Morphology and Physiology: Rationale and Study Design.

Computed tomographic coronary angiography (CTCA) is a non-invasive imaging modality, which allows plaque burden and composition assessment and detection of plaque characteristics associated with increased vulnerability. In addition, CTCA-based coronary artery reconstruction enables local haemodynamic forces assessment, which regulate plaque formation and vascular inflammation and prediction of lesions that are prone to progress and cause events. However, the use of CTCA for vulnerable plaque detection in the clinical arena remains limited. To unlock the full potential of CTCA and enable its broad use, further work is needed to develop user-friendly processing tools that will allow fast and accurate analysis of CTCA, computational fluid dynamic modelling, and evaluation of the local haemodynamic forces. The present study aims to develop a seamless platform that will overcome the limitations of CTCA and enable fast and accurate evaluation of plaque morphology and physiology. We will analyse imaging data from 70 patients with coronary artery disease who will undergo state-of-the-art CTCA and near-infrared spectroscopy-intravascular ultrasound imaging and develop and train algorithms that will take advantage of the intravascular imaging data to optimise vessel segmentation and plaque characterisation. Furthermore, we will design an advanced module that will enable reconstruction of coronary artery anatomy from CTCA, blood flow simulation, shear stress estimation, and comprehensive visualisation of vessel pathophysiology. These advances are expected to facilitate the broad use of CTCA, not only for risk stratification but also for the evaluation of the effect of emerging therapies on plaque evolution.

Antiinflammatory actions of inorganic nitrate stabilize the atherosclerotic plaque.

Reduced bioavailable nitric oxide (NO) plays a key role in the enhanced leukocyte recruitment reflective of systemic inflammation thought to precede and underlie atherosclerotic plaque formation and instability. Recent evidence demonstrates that inorganic nitrate (NO3-) through sequential chemical reduction in vivo provides a source of NO that exerts beneficial effects upon the cardiovascular system, including reductions in inflammatory responses. We tested whether the antiinflammatory effects of inorganic nitrate might prove useful in ameliorating atherosclerotic disease in Apolipoprotein (Apo)E knockout (KO) mice. We show that dietary nitrate treatment, although having no effect upon total plaque area, caused a reduction in macrophage accumulation and an elevation in smooth muscle accumulation within atherosclerotic plaques of ApoE KO mice, suggesting plaque stabilization. We also show that in nitrate-fed mice there is reduced systemic leukocyte rolling and adherence, circulating neutrophil numbers, neutrophil CD11b expression, and myeloperoxidase activity compared with wild-type littermates. Moreover, we show in both the ApoE KO mice and using an acute model of inflammation that this effect upon neutrophils results in consequent reductions in inflammatory monocyte expression that is associated with elevations of the antiinflammatory cytokine interleukin (IL)-10. In summary, we demonstrate that inorganic nitrate suppresses acute and chronic inflammation by targeting neutrophil recruitment and that this effect, at least in part, results in consequent reductions in the inflammatory status of atheromatous plaque, and suggest that this effect may have clinical utility in the prophylaxis of inflammatory atherosclerotic 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.

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.

The effect of CTCA guided selective invasive graft assessment on coronary angiographic parameters and outcomes: Insights from the BYPASS-CTCA trial.

BACKGROUND: Computed tomography cardiac angiography (CTCA) is recommended for the evaluation of patients with prior coronary artery bypass graft (CABG) surgery. The BYPASS-CTCA study demonstrated that CTCA prior to invasive coronary angiography (ICA) in CABG patients leads to significant reductions in procedure time and contrast-induced nephropathy (CIN), alongside improved patient satisfaction. However, whether CTCA information was used to facilitate selective graft cannulation at ICA was not protocol mandated. In this post-hoc analysis we investigated the influence of CTCA facilitated selective graft assessment on angiographic parameters and study endpoints. METHODS: BYPASS-CTCA was a randomized controlled trial in which patients with previous CABG referred for ICA were randomized to undergo CTCA prior to ICA, or ICA alone. In this post-hoc analysis we assessed the impact of selective ICA (grafts not invasively cannulated based on the CTCA result) following CTCA versus non-selective ICA (imaging all grafts irrespective of CTCA findings). The primary endpoints were ICA procedural duration, incidence of CIN, and patient satisfaction post-ICA. Secondary endpoints included the incidence of procedural complications and 1-year major adverse cardiac events. RESULTS: In the CTCA cohort (n â€‹= â€‹343), 214 (62.4%) patients had selective coronary angiography performed, whereas 129 (37.6%) patients had non-selective ICA. Procedure times were significantly reduced in the selective CTCA â€‹+ â€‹ICA group compared to the non-selective CTCA â€‹+ â€‹ICA group (-5.82min, 95% CI -7.99 to -3.65, p â€‹< â€‹0.001) along with reduction of CIN (1.5% vs 5.8%, OR 0.26, 95% CI 0.10 to 0.98). No difference was seen in patient satisfaction with the ICA, however procedural complications (0.9% vs 4.7%, OR 0.21, 95% CI 0.09-0.87) and 1-year major adverse cardiac events (13.1% vs 20.9%, HR 0.55, 95% CI 0.32-0.96) were significantly lower in the selective group. CONCLUSIONS: In patients with prior CABG, CTCA guided selective angiographic assessment of bypass grafts is associated with improved procedural parameters, lower complication rates and better 12-month outcomes. Taken in addition to the main findings of the BYPASS-CTCA trial, these results suggest a synergistic approach between CTCA and ICA should be considered in this patient group. REGISTRATION: ClinicalTrials.gov, NCT03736018.

Deployment of drug-eluting stents for isolated proximal lad disease is associated with lower major adverse cardiac events and no increase in stent thrombosis when compared with bare metal stents: a 5-year observational cohort study.

BACKGROUND: Drug-eluting stents (DES) may be associated with an increased risk of late stent thrombosis (ST) compared with bare metal stents (BMS). We compared major adverse cardiac events (MACE) and long term all cause mortality in patients with isolated proximal LAD disease treated with DES or BMS. METHOD AND RESULTS: This study of 1653 patients with isolated proximal LAD disease, includes 643 treated with BMS and 1010 treated with DES. All patients received standard dual antiplatelet treatment. MACE after 5 years were less frequent in DES compared with BMS (12.1% 95% CI 9.3-14.2 versus 21.3% 95% CI: 16.9-25.1, P < 0.0001), driven largely by a decreased rate of both target vessel and lesion revascularization (TVR: 6.3%, 95% CI 4.0-7.5% versus 14.7%, 95% CI 11.0-17.3%, P < 0.0001, TLR: (5.3%, 95% CI 3.2-7.1% versus 13.2%, 95% CI 9.8.0-15.4%, P < 0.0001). There was no difference in the rate of death, myocardial infarction, or CVA. Incidence of stent thrombosis was also comparable (1.2% 95% CI: 0.6-2.6% versus 1.1% 95% CI: 0.6-2.5%, P = 0.8). Adjusted Cox analysis confirmed a decreased risk of MACE for DES compared with BMS 0.55 (95% confidence intervals 0.41-0.73) with no difference in the hazard of all cause mortality (HR: 1.04 95% CI: 0.67-1.61). CONCLUSION: When treating proximal LAD disease, use of DES was associated with a lower MACE rate than BMS, with no differences in the incidence of stent thrombosis, myocardial infarction or 5 year all cause mortality. Our data suggests that despite the adverse prognostic correlates of proximal LAD disease, DES deployment in this location is both safe and clinically more effective than BMS.

Characteristics and outcomes of dialysis patients with infective endocarditis.

BACKGROUND: The incidence of infective endocarditis (IE) in dialysis patients is higher than the general population. Dialysis patients who develop endocarditis are thought to have a poorer prognosis than other patients with IE. AIM: To examine the risk profiles, clinical features, and outcomes of patients on dialysis who developed IE in a large cohort. DESIGN AND METHODS: A retrospective analysis of all patients developing IE on dialysis (using the modified Duke criteria) was undertaken between 1998 and 2011. Patients were identified from a prospectively collected clinical database. RESULTS: 42 patients developed IE out of a total incident dialysis population of 1,500 over 13 years. 95% of the patients (40/42) were on long-term haemodialysis (HD) and 5% (2/42) on peritoneal dialysis. Mean patient age was 55.2 years (IQR: 43-69), and mean duration of HD prior to IE was 57.4 months. Primary HD access at the time of diagnosis was an arteriovenous fistula in 35% (14/40), a dual-lumen tunnelled catheter in 55% (22/40), and a dual-lumen non-tunnelled catheter in 10% (4/40). Staphylococcus aureus (including methicillin-resistant S. aureus) was present in 57.1% (24/42). The aortic valve was affected in 42.8% of the patients (18/42), the mitral valve in 30.9% (13/42), and both valves in 9.5% (4/42). 33.3% of the patients had an abnormal valve before the episode of IE. In 21.4% (9/42), valve surgery was performed and mortality was lower in the surgical group compared to the group managed medically during hospitalisation (11.1 vs. 15.2%, p = 0.892), at 3 months (13.1 vs. 19.6%, p = 0.501), and during follow-up (p = 0.207), but this difference did not reach statistical significance. Age >60 years, septic emboli, and methicillin-resistant S. aureus were all adverse prognostic factors. Patients receiving surgery were younger (mean 47.1 ± 14.4 years vs. 57.4 ± 14.3, p = 0.049) and less likely to be infected with S. aureus (surgery 33.3% vs. antibiotics 63.6%, p = 0.046). CONCLUSION: This is one of the largest reported series of IE in dialysis patients. The incidence of IE remains high and the prognosis poor in dialysis patients, although patients selected for early valve surgery have good 1-year survival.

An observational study assessing the use of Sirolimus-eluting balloons for side-branch treatment in the provisional stenting of coronary bifurcations.

Background: Drug eluting balloons (DEB) are a feasible method of rapid delivery of drug to a coronary vessel wall. Their efficacy has been established for the treatment of in-stent restenosis and small vessel disease but there is limited data for their use in bifurcation lesions. Objective: The aim of this study was to assess the effectiveness of provisional upfront side-branch DEB use in bifurcation lesions compared to a simple balloon (POBA) or upfront 2 stent bifurcation strategy. Methods: We conducted an observational study of 625 patients undergoing PCI to bifurcation lesions. All the patients had a DES deployed in the main vessel (MV). Decision on revascularization option for the side branch (SB) was made by the operator. The primary endpoint was target vessel failure. Secondary endpoints were target vessel myocardial infarction and all-cause mortality. Results: 311 patients had upfront DEB to the SB whilst the remaining were treated with either DES (188) or POBA (126). Baseline characteristics were similar aside from history of previous MI, which were higher in patients treated with DES or POBA, p = 0.009 whereas patients with previous CABG were likely to undergo DEB treatment (p = 0.004). TVF was more likely to occur in the POBA group (7.5 %) compared to the DEB (3.3 %) and DES (3.3 %) groups (p = 0.0019). There was no significant difference in TV-MI (p = 0.62) or death (p = 0.98) between the groups. Conclusion: This study suggests that provisional bifurcation stenting with upfront Sirolimus DEB use in the SB is an effective treatment for non-LMS bifurcation PCI.

The safety of deferred coronary angiography in COVID-19 patients with acute coronary syndrome: the Barts COVID recovered pathway.

OBJECTIVE: To assess the safety and effectiveness of a novel pathway of deferrred invasive angiography in low-risk NSTEMI patients with concurrent COVID-19 infections; contrary to current UK guidelines recommending invasive coronary angiography in NSTEMI patients within 72 hours. METHODS: This was a single-centre, observational study of all NSTEMI patients referred for inpatient coronary angiography at Barts Heart Centre, between March 2020 and June 2022. Demographic, procedural and outcome data were collected as part of a national cardiac audit. RESULTS: 201 COVID positive NSTEMI patients were referred for angiography at Barts Heart Centre. 10 patients died from COVID related respiratory complications prior to angiography. Therefore, 191 patients underwent deferred angiography (median time 16 days from COVID diagnosis). The median GRACE score was 128 (IQR 86-153). Troponin levels were significantly elevated on initial COVID diagnosis compared to time of their procedure. 73% patients had a culprit lesion identified. 61.2% receiving PCI. Patients were followed-up for a median of 363 days (IQR 120-485 days) with MACE rates of 7.3%. This is comparable to the MACE event for NSTEMI patients (n=4529) without COVID at our institution treated during the same time-period (8.1%). CONCLUSION: This study demonstrates the safety and effectiveness of deferred coronary angiography on a COVID-Recovered pathway after a period of medical management for patients presenting with NSTEMI and concurrent COVID-19 infection. There was no adverse signal associated with the wait for angiography with similar MACE rates to the non-deferred NSTEMI cohort without COVID-19.

A double-blind, randomised, placebo-controlled parallel study to investigate the effect of sex and dietary nitrate on COVID-19 vaccine-induced vascular dysfunction in healthy men and women: protocol of the DiNOVasc-COVID-19 study.

BACKGROUND: Cardiovascular events, driven by endothelial dysfunction, are a recognised complication of COVID-19. SARS-CoV-2 infections remain a persistent concern globally, and an understanding of the mechanisms causing endothelial dysfunction, particularly the role of inflammation, nitric oxide, and whether sex differences exist in this response, is lacking. We have previously demonstrated important sex differences in the inflammatory response and its impact on endothelial function and separately that the ingestion of inorganic nitrate can protect the endothelium against this dysfunction. In this study, we will investigate whether sex or a dietary inorganic nitrate intervention modulates endothelial function and inflammatory responses after the COVID-19 vaccine. METHODS: DiNOVasc-COVID-19 is a double-blind, randomised, single-centre, placebo-controlled clinical trial. A total of 98 healthy volunteers (49 males and 49 females) will be recruited. Participants will be randomised into 1 of 2 sub-studies: part A or part B. Part A will investigate the effects of sex on vascular and inflammatory responses to the COVID-19 vaccine. Part B will investigate the effects of sex and dietary inorganic nitrate on vascular and inflammatory responses to the COVID-19 vaccine. In part B, participants will be randomised to receive 3 days of either nitrate-containing beetroot juice (intervention) or nitrate-deplete beetroot juice (placebo). The primary outcome for both sub-studies is a comparison of the change in flow-mediated dilatation (FMD) from baseline after COVID-19 vaccination. The study has a power of > 80% to assess the primary endpoint. Secondary endpoints include change from baseline in inflammatory and leukocyte counts and in pulse wave analysis (PWA) and pulse wave velocity (PWV) following the COVID-19 vaccination. DISCUSSION: This study aims to evaluate whether sex or dietary influences endothelial function and inflammatory responses in healthy volunteers after receiving the COVID-19 vaccine. TRIAL REGISTRATION: ClinicalTrials.gov NCT04889274. Registered on 5 May 2023. The study was approved by the South Central - Oxford C Research Ethics Committee (21/SC/0154).

Thrombus Burden and Outcomes in Patients With COVID-19 Presenting With STEMI Across the Pandemic.

BACKGROUND: It has been previously reported during the first COVID-19 outbreak that patients presenting with ST-segment elevation myocardial infarction (STEMI) and concurrent COVID-19 infection have increased thrombus burden and poorer outcomes. To date, there have been no reports comparing the outcomes of COVID-19-positive STEMI patients across all waves of the pandemic. OBJECTIVES: This study compared the baseline demographic, procedural, and angiographic characteristics alongside the clinical outcomes of patients presenting with STEMI and concurrent COVID-19 infection across the COVID-19 pandemic in the United Kingdom. METHODS: This was a single-center, observational study of 1,269 consecutive patients admitted with confirmed STEMI treated with percutaneous coronary intervention (between January 3, 2020 and October 3, 2022). COVID-19-positive patients were split into 3 groups based upon the time course of the pandemic, and a comparison was made between waves. RESULTS: A total of 154 COVID-19-positive patients with STEMI were included in the present analysis and were compared with 1,115 COVID-19-negative patients. Early during the pandemic (wave 1), STEMI patients presenting with concurrent COVID-19 infection had high rates of cardiac arrest, evidence of increased thrombus burden, bigger infarcts, and worse outcomes. However, by wave 3, no differences existed in outcomes between COVID-19-positive and -negative patients, with significant differences compared with earlier COVID-19-positive patients. Poor outcomes later in the study period were predominantly in unvaccinated individuals. CONCLUSIONS: Significant changes have occurred in the clinical characteristics, angiographic features, and outcomes of STEMI patients with COVID-19 infection treated by primary percutaneous coronary intervention during the course of the pandemic. Importantly, outcomes of recent waves and in vaccinated individuals are no different to a non-COVID-19 population.

An exploration of the early discharge approach for low-risk STEMI patients following primary percutaneous coronary intervention.

Recently, there has been growing interest in the early discharge strategy for low-risk patients who have undergone primary percutaneous coronary intervention (PCI) to treat ST-segment elevation myocardial infarction (STEMI). So far findings have suggested there are multiple advantages of shorter hospital stays, including that it could be a safe way to be more cost- and resource-efficient, reduce cases of hospital-acquired infection and boost patient satisfaction. However, there are remaining concerns surrounding safety, patient education, adequate follow-up and the generalisability of the findings from current studies which are mostly small-scale. By assessing the current research, we describe the advantages, disadvantages and challenges of early hospital discharge for STEMI and discuss the factors that determine if a patient can be considered low risk. If it is feasible to safely employ a strategy like this, the implications for healthcare systems worldwide could be extremely beneficial, particularly in lower-income economies and when we consider the detrimental impacts of the recent COVID-19 pandemic on healthcare systems.

Delayed Diagnosis of Compartment Syndrome After Transradial PCI, Leading to Long-Term Disability.

The transradial access approach is a well-established route for coronary angiography and percutaneous intervention, given its lower complication rate over the transfemoral route. However, complications are still apparent, some of which can lead to serious injury. We report a case of delayed diagnosis of localized compartment syndrome, caused by haematoma and pseudoaneurysm formation following a radial procedure which resulted in long term disability. We emphasize the importance of early recognition and diagnosis of compartment syndrome to avoid long term sequalae.

An Observational Study Assessing the Predictors of Procedural Failure From the Radial Approach: Is Right Radial Access Always the Best?

OBJECTIVE: The study aimed to determine the predictors of procedural failure (coronary cannulation) in patients undergoing coronary angiography ± percutaneous coronary intervention (PCI) from the transradial (TR) approach. METHODS: We conducted an observational study of 20,315 consecutive patients undergoing TR angiography between 2016 and 2020. TR failure was described as inability to cannulate the coronary arteries. Univariate and multivariate analyses were performed to determine independent predictors of TR failure. RESULTS: Out of the study population, TR failure was observed in 365 (1.8%) patients, out of which 281 (77%) crossed over successfully to the transfemoral (TF) route and 84 (23%) to left radial access (LRA). Unsuccessful procedures were most likely seen in patients who were elderly, female, BAME background, short stature or with a history of hypertension, diabetes, and renal disease. On regression analysis, age (OR: 1.024; 95% Cl: 1.014-1.035), female gender (OR: 0.729; 95% Cl: 0.555-0.957), BAME (OR: 0.786; 95% Cl: 0.612-0.959), height (OR: 0.988; 95% Cl: 0.977-0.999), hypertension (OR: 1.510; 95% Cl: 1.147-1.987) and RRA (OR: 1.977; 95% Cl: 1.105-3.538) were independent predictors of TR failure. On further analysis, these predictors of failure were not seen from the LRA approach. CONCLUSION: This study identifies that rates of TR failure are low and that predictors of failure differ between the RRA and LRA. The difference in predictors between the 2 routes suggests that in patients when coronary cannulation is unsuccessful via the RRA then the LRA could be considered as a second access site. Further study is needed to see if in selected patient groups the LRA could be used as the first-choice access route.

Treatment Strategies and Outcomes of Emergency Left Main Percutaneous Coronary Intervention.

Emergency percutaneous coronary intervention of the left main (LM ePCI) coronary artery necessitated by acute coronary syndrome is associated with a high risk of mortality. However, optimal treatment strategies and related outcomes remain undefined in this group. We undertook a multi-center, retrospective, observational cohort study of consecutive patients requiring LM ePCI between 2011 and 2018 and reported the coronary anatomy, treatment strategies, outcomes, and predictors of mortality. A total of 116 consecutive cases were included. Patients were predominantly male (85%) with a median age of 68.0 years; 12 patients (10%) had previous coronary artery bypass grafting. ST-elevation was noted in 76 (66%); 30 (26%) presented with an out-of-hospital cardiac arrest (OOHCA) and 47 (41%) with cardiogenic shock. The most frequent pattern of disease was Medina 1,1,1, seen in 59 patients (51%). The commonest revascularization strategy was provisional stenting (95 cases, 82%) with improved or thrombolysis in myocardial infarction 3 flow seen in 85 cases (73%). All-cause mortality was 35% at 30 days, rising to 58% at 5 years. Adverse predictors of 30-day mortality included presentation with cardiogenic shock (p = 0.018) and OOHCA (p = 0.020), whereas improved flow and/or thrombolysis in myocardial infarction 3 flow in both circumflex and left anterior descending artery afforded a better prognosis (p = 0.028). In conclusion, patients who underwent LM ePCI are a high-risk subgroup and commonly present with cardiogenic shock and OOHCA. Provisional stenting appears to be the preferred option with the successful restoration of coronary flow in most cases despite complex anatomy. High 30-day mortality is driven by the presence of cardiogenic shock, OOHCA, and failure to restore or improve coronary flow.

Quantitative Myocardial Perfusion Predicts Outcomes in Patients With Prior Surgical Revascularization.

BACKGROUND: Patients with previous coronary artery bypass graft (CABG) surgery typically have complex coronary disease and remain at high risk of adverse events. Quantitative myocardial perfusion indices predict outcomes in native vessel disease, but their prognostic performance in patients with prior CABG is unknown. OBJECTIVES: In this study, we sought to evaluate whether global stress myocardial blood flow (MBF) and perfusion reserve (MPR) derived from perfusion mapping cardiac magnetic resonance (CMR) independently predict adverse outcomes in patients with prior CABG. METHODS: This was a retrospective analysis of consecutive patients with prior CABG referred for adenosine stress perfusion CMR. Perfusion mapping was performed in-line with automated quantification of MBF. The primary outcome was a composite of all-cause mortality and major adverse cardiovascular events defined as nonfatal myocardial infarction and unplanned revascularization. Associations were evaluated with the use of Cox proportional hazards models after adjusting for comorbidities and CMR parameters. RESULTS: A total of 341 patients (median age 67 years, 86% male) were included. Over a median follow-up of 638 days (IQR: 367-976 days), 81 patients (24%) reached the primary outcome. Both stress MBF and MPR independently predicted outcomes after adjusting for known prognostic factors (regional ischemia, infarction). The adjusted hazard ratio (HR) for 1 mL/g/min of decrease in stress MBF was 2.56 (95% CI: 1.45-4.35) and for 1 unit of decrease in MPR was 1.61 (95% CI: 1.08-2.38). CONCLUSIONS: Global stress MBF and MPR derived from perfusion CMR independently predict adverse outcomes in patients with previous CABG. This effect is independent from the presence of regional ischemia on visual assessment and the extent of previous infarction.

Inorganic nitrate attenuates cardiac dysfunction: roles for xanthine oxidoreductase and nitric oxide.

BACKGROUND AND PURPOSE: NO is a vasodilator and independent modulator of cardiac remodelling. Commonly, in cardiac disease (e.g., heart failure), endothelial dysfunction (synonymous with NO deficiency) has been implicated in increased BP, cardiac hypertrophy and fibrosis. Currently, no effective therapies replacing NO have succeeded in the clinic. Inorganic nitrate (NO3 - ), through chemical reduction to nitrite and then to NO, exerts potent BP lowering, but whether it might be useful in treating undesirable cardiac remodelling is not known. EXPERIMENTAL APPROACH: We analysed demographics in a nested age- and sex-matched case-control study of hypertensive patients with or without left ventricular hypertrophy (NCT03088514) and assessed the effects of dietary nitrate in mouse models of cardiac dysfunction. KEY RESULTS: Lower plasma nitrite concentrations and vascular dysfunction accompanied cardiac hypertrophy and fibrosis in patients. In mouse models of cardiac remodelling, restoration of circulating nitrite levels using dietary nitrate improved endothelial dysfunction through targeting the xanthine oxidoreductase-driven increase in levels of H2 O2 and superoxide, and decreased cardiac fibrosis through NO-mediated block of SMAD phosphorylation leading to improvements in cardiac structure and function. CONCLUSIONS AND IMPLICATIONS: Dietary nitrate offers easily translatable therapeutic options for delivery of NO and thereby treatment of cardiac dysfunction.