Transcoronary electrophysiological parameters in patients undergoing elective and acute coronary intervention.

INTRODUCTION: Percutaneous coronary intervention is performed routinely in the management of myocardial infarction with obstructive coronary disease, but intervention to arteries supplying nonviable myocardium may be harmful. It is important therefore to establish myocardial viability, and there is an unmet need in current clinical practice for real time viability assessment to aid in decision making. Transcoronary pacing to assess myocardial electrophysiological parameters may be a novel viability assessment technique which could be used in this regard. METHODS: Coronary intervention was carried out according to standard departmental procedure with standard equipment. An exchange length coronary guidewire was passed into both target and reference coronary vessels and an over-the-wire balloon or microcatheter was used to insulate the guidewire and allow electrophysiological parameters to be assessed. Readings were obtained from all major epicardial vessels and substantial branches. At each position, an intracoronary electrocardiogram was recorded, and R wave amplitude was measured. Transcoronary pacing was then performed to establish threshold and impedance for each myocardial segment. A viability cardiac MRI scan was performed for each patient. A standard segmental model was used to determine viability in each segment using an 'infarct score' based on degree of late gadolinium enhancement. Studies were reported blinded to the electrical parameters obtained from the coronary guidewire. The primary outcome was the relationship between pacing threshold and myocardial segment infarct score. Secondary outcomes included the relationship between segmental infarct score and R wave height, and between segmental infarct score and pacing impedance. Data were collected on the feasibility of studying the coronary segments as well as safety. RESULTS: Sixty-five patients presenting with stable coronary artery disease or acute coronary syndromes to Leeds General Infirmary between September 2019 and August 2021 were included in the study. Electrophysiological parameters from segments with an infarct score of zero were obtained, with wide variances seen, with no significant difference in impedance or threshold in any territory. There was a significant difference in sensitivity for segments in the right coronary artery territory for both elective and acute patients. This likely relates to reduced myocardial mass in these territories. No significant association between infarct score and sensitivity, impedance or threshold were seen. CONCLUSION: This study has established intracoronary electrophysiological parameters in both normal myocardium and areas of myocardial scar. No reliable association was seen between impedance, threshold or R wave amplitude and degree of myocardial viability, contrasting with prior findings from our group and others. More work is therefore required to fully understand the role of transcoronary pacing in this setting.

Fractional Flow Reserve versus Angiography-Guided Management of Coronary Artery Disease: A Meta-Analysis of Contemporary Randomised Controlled Trials.

Background and Aims: Randomised controlled trials (RCTs) comparing outcomes after fractional flow reserve (FFR)-guided versus angiography-guided management for obstructive coronary artery disease (CAD) have produced conflicting results. We investigated the efficacy and safety of an FFR-guided versus angiography-guided management strategy among patients with obstructive CAD. Methods: A systematic electronic search of the major databases was performed from inception to September 2022. We included studies of patients presenting with angina or myocardial infarction (MI), managed with medications, percutaneous coronary intervention, or bypass graft surgery. A meta-analysis was performed by pooling the risk ratio (RR) using a random-effects model. The endpoints of interest were all-cause mortality, MI and unplanned revascularisation. Results: Eight RCTs, with outcome data from 5077 patients, were included. The weighted mean follow up was 22 months. When FFR-guided management was compared to angiography-guided management, there was no difference in all-cause mortality [3.5% vs. 3.7%, RR: 0.99 (95% confidence interval (CI) 0.62−1.60), p = 0.98, heterogeneity (I2) 43%], MI [5.3% vs. 5.9%, RR: 0.93 (95%CI 0.66−1.32), p = 0.69, I2 42%], or unplanned revascularisation [7.4% vs. 7.9%, RR: 0.92 (95%CI 0.76−1.11), p = 0.37, I2 0%]. However, the number patients undergoing planned revascularisation by either stent or surgery was significantly lower with an FFR-guided strategy [weighted mean difference: 14 (95% CI 3 to 25)%, p =< 0.001]. Conclusion: In patients with obstructive CAD, an FFR-guided management strategy did not impact on all-cause mortality, MI and unplanned revascularisation, when compared to an angiography-guided management strategy, but led to up to a quarter less patients needing revascularisation.

Safety and efficacy of interrupting dual antiplatelet therapy one month following percutaneous coronary intervention: a meta-analysis of randomized controlled trials.

Very short duration of dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) has recently attracted a lot of attention with the introduction of newer generations stents. This is appealing, especially in patients at high bleeding risk. However, none of the trials were powered for the individual ischemic and bleeding endpoints. All randomised controlled trials (RCTs) investigating one-month versus routine duration of DAPT in patients undergoing PCI and reporting outcomes from the time of cessation of DAPT (1 month) to 1 year were eligible for inclusion in the meta-analysis. The pooled risk ratios (RR) with their 95% confidence interval (CI) were calculated with the random-effects model using the Mantel-Haenszel method. Four RCTs involving 26,576 patients were included in this meta-analysis. Cessation of DAPT after 1 month was associated with significantly less major bleeding [RR 0.70, 95%CI (0.51-0.95), P = 0.02, heterogeneity (I2) = 42%]. There was no statistically significant difference in all-cause mortality [RR 0.84 (95%CI 0.69-1.03), P = 0.10, I2 = 0%] and stroke [RR 0.71 (95%CI 0.45-1.13), P = 0.15, I2 = 42%] when compared to routine duration of DAPT. There was also no difference in myocardial infarction (MI) [RR 1.12 (95%CI 0.91-1.39), P = 0.28, I2 = 0%], and definite or probable stent thrombosis [RR 1.49 (95%CI 0.92-2.41), P = 0.11, I2 = 0%] with cessation of DAPT after 1 month. Cessation of DAPT 1 month after PCI was associated with significantly less major bleeding, but there was no difference in the rate of all-cause mortality, stroke, MI and stent thrombosis.

Five-year clinical outcomes in patients with frailty aged ≥75 years with non-ST elevation acute coronary syndrome undergoing invasive management.

Aim: Frailty is associated with adverse outcomes in older patients with acute coronary syndrome (ACS). The impact of frailty on long-term clinical outcomes following invasive management of non-ST elevation ACS (NSTEACS) is unknown. Methods and results: The multi-centre Improve Clinical Outcomes in high-risk patieNts with ACS 1 (ICON-1) prospective cohort study consisted of patients aged >75 years undergoing coronary angiography following NSTEACS. Patients were categorized by frailty assessed by Canadian Study of Health and Ageing Clinical Frailty Scale (CFS) and Fried criteria. The primary composite endpoint was all-cause mortality, unplanned revascularization, myocardial infarction, stroke, and bleeding. Of 263 patients, 33 (12.5%) were frail, 152 (57.8%) were pre-frail, and 78 (29.7%) were robust according to CFS. By Fried criteria, 70 patients (26.6%, mean age 82.1 years) were frail, 147 (55.9%, mean age 81.3 years) were pre-frail, and 46 (17.5%, mean age 79.9 years) were robust. The composite endpoint was more common at 5 years among patients with frailty according to CFS (frail: 22, 66.7%; pre-frail: 81, 53.3%; robust: 27, 34.6%, P = 0.003), with a similar trend when using Fried criteria (frail: 39, 55.7%; pre-frail: 72, 49.0%; robust: 16, 34.8%, P = 0.085). Frailty measured with both CFS and Fried criteria was associated with the primary endpoint [age and sex-adjusted hazard ratio (HR) compared with robust groups. CFS: 2.22, 95% confidence interval (CI) 1.23-4.02, P = 0.008; Fried: HR 1.81, 95% CI 1.00-3.27, P = 0.048]. Conclusion: In older patients who underwent angiography following NSTEACS, frailty is associated with an increased risk of the primary composite endpoint at 5 years. Registration: Clinicaltrials.gov NCT01933581.

Is the contemporary care of the older persons with acute coronary syndrome evidence-based?

Globally, ischaemic heart disease is the leading cause of death, with a higher mortality burden amongst older adults. Although advancing age is associated with a higher risk of adverse outcomes following acute coronary syndrome (ACS), older patients are less likely to receive evidence-based medications and coronary angiography. Guideline recommendations for managing ACS are often based on studies that exclude older patients, and more contemporary trials have been underpowered and produced inconsistent findings. There is also limited evidence for how frailty and comorbidity should influence management decisions. This review focuses on the current evidence base for the medical and percutaneous management of ACS in older patients and highlights the distinct need to enrol older patients with ACS into well-powered, large-scale randomized trials.

Frailty Scores and Their Utility in Older Patients with Cardiovascular Disease.

The world's population is ageing, resulting in more people with frailty receiving treatment for cardiovascular disease (CVD). The emergence of novel interventions, such as transcatheter aortic valve implantation, has also increased the proportion of older patients being treated in later stages of life. This increasing population burden makes the assessment of frailty of utmost importance, especially in patients with CVD. Despite a growing body of evidence on the association between frailty and CVD, there is no consensus on the optimal frailty assessment tool for use in clinical settings. Previous studies have shown limited concordance between validated frailty instruments. This review evaluates the evidence on the utility of frailty assessment tools in patients with CVD, and the effect of frailty on different outcomes measured.

Coronary artery lesion phenotype in frail older patients with non-ST-elevation acute coronary syndrome undergoing invasive care.

AIMS: The association of frailty with coronary plaque phenotype among older patients with non-ST-elevation acute coronary syndrome (NSTEACS) is not known. The aim of this study was to evaluate the association of frailty with coronary plaque phenotype among older patients with NSTEACS. METHODS AND RESULTS: Older patients with NSTEACS who underwent invasive angiography were recruited. Frailty was measured using the Fried frailty score. Following angiography, patients underwent greyscale and virtual histology intravascular ultrasound (VH-IVUS) imaging. Of the 90 patients, 26 (28.9%) were robust, 49 (54.4%) patients were pre-frail, and 15 (16.7%) were frail. Mean age was 80.9±3.8 years; 59 (65.6%) were male. Compared to robust patients, the pre-frail group had a significantly greater presence of high-risk lesions including VH thin-cap fibroatheroma (TCFA, p=0.011), minimum lumen area (MLA) ≤4 mm2 (p=0.016), TCFA+MLA ≤4 mm2 (p=0.005), TCFA+plaque burden (PB) ≥70% (p=0.005) and TCFA+PB ≥70%+MLA ≤4 mm2 (p=0.003). By age- and sex-adjusted logistic regression analysis, frailty was found to be strongly and independently associated with the presence of TCFA (odds ratio [OR] 2.81, 95% confidence interval [CI]:1.06-7.48, p=0.039). CONCLUSIONS: This is the first study to report the relationship between frailty phenotype and coronary plaque morphology among frail older NSTEACS patients. ClinicalTrials.gov Identifier: NCT01933581.

One-year clinical outcomes in older patients with non-ST elevation acute coronary syndrome undergoing coronary angiography: An analysis of the ICON1 study.

AIMS: The aim of this prospective, observational study was to identify predictors of adverse outcome at one year, following invasive care of older patients with non-ST-elevation acute coronary syndrome (NSTEACS) according to frailty status. METHODS: Older patients (aged ≥ 75 years), presenting with NSTEACS, undergoing invasive coronary angiography with a view to revascularisation, underwent assessment of frailty, cognition, functional status and quality of life. Participants were categorised as robust, pre-frail or frail using the Fried criteria. The primary outcome comprised a composite of all-cause mortality, myocardial infarction, stroke, unplanned revascularisation and major bleeding, at one year. Cox proportional hazards regression was used to derive a multivariate risk score. RESULTS: Overall, the composite endpoint was observed in 81 participants (29%). There was a significant difference in the occurrence of the primary outcome in the 3 frailty groups (robust 18.0%, pre-frail 27.5% and frail 39%; p = 0.03; hazard ratio (HR) for frail vs. robust: 2.79, 95% Confidence Interval [CI] 1.28-6.08). Fried frailty classification, age (categorised as ≥85 years), raised Killip class, systolic blood pressure on admission, history of peripheral vascular disease (PVD), problems dressing self and implantation of a bare metal stent were identified as predictors of adverse events at one year, with a C-statistic of 0.77 (95% CI 0.71-0.83). A point-based clinical risk score (FRAIL-HEART) was defined, which had a C-statistic of 0.70 (95% CI 0.63-0.77) and significantly outperformed the GRACE 2 score. CONCLUSION: Frailty is associated with adverse clinical outcomes, following invasive management of older patients with NSTEACS. The derived risk models may enable improved risk stratification in practice.

The effect of percutaneous coronary intervention on habitual physical activity in older patients.

BACKGROUND: Given the ongoing burden of cardiovascular disease and an ageing population, physical activity in patients with coronary artery disease needs to be emphasized. This study assessed whether sedentary behaviour and physical activity levels differed among older patients (≥75 years) following percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) consisting of ST-segment elevation myocardial infarction (STEMI) and non STEMI (NSTEMI) versus an elective admission control group of stable angina patients. METHODS: Sedentary behaviour and physical activity were assessed over a 7-day period using wrist-worn triaxial accelerometers (GENEActiv, Activinsights Ltd, UK) in 58 patients following PCI for, STEMI (n = 20) NSTEMI (n = 18) and stable angina (n = 20) upon discharge from a tertiary centre. Mean ± Standard deviation age was 79 ± 4 years (31% female). RESULTS: STEMI and NSTEMI patients spent more time in the low acceleration category (0-40 mg) reflecting sedentary time versus stable angina patients (1298 ± 59 and 1305 ± 66 vs. 1240 ± 92 min/day, p < 0.05). STEMI and NSTEMI patients spent less time in the 40-80 mg acceleration category reflecting low physical activity versus stable angina patients (95 ± 35 and 94 ± 41 vs. 132 ± 50 min/day, p < 0.05). Stable angina patients spent more time in the higher acceleration categories (80-120 and 120-160 mg) and moderate-to-vigorous physical activity (defined as 1 and 5 min/day bouts) versus NSTEMI patients (p < 0.05). For acceleration categories ≥160 mg, no differences were observed. CONCLUSIONS: Patients presenting with ACS and undergoing PCI spent more time in sedentary behaviour compared with stable angina patients.

Study to Improve Cardiovascular Outcomes in high-risk older patieNts (ICON1) with acute coronary syndrome: study design and protocol of a prospective observational study.

INTRODUCTION: The ICON1 study (a study to Improve Cardiovascular Outcomes in high-risk older patieNts with acute coronary syndrome) is a prospective observational study of older patients (≥75 years old) with non-ST-elevation acute coronary syndrome managed by contemporary treatment (pharmacological and invasive). The aim of the study was to determine the predictors of poor cardiovascular outcomes in this age group and to generate a risk prediction tool. METHODS AND ANALYSIS: Participants are recruited from 2 tertiary hospitals in the UK. Baseline evaluation includes frailty, comorbidity, cognition and quality-of-life measures, inflammatory status assessed by a biomarker panel, including microRNAs, senescence assessed by telomere length and telomerase activity, cardiovascular status assessed by arterial stiffness, endothelial function, carotid intima media thickness and left ventricular systolic and diastolic function, and coronary plaque assessed by virtual histology intravascular ultrasound and optical coherence tomography. The patients are followed-up at 30 days and at 1 year for primary outcome measures of death, myocardial infarction, stroke, unplanned revascularisation, bleeding and rehospitalisation. ETHICS AND DISSEMINATION: The study has been approved by the regional ethics committee (REC 12/NE/016). Findings of the study will be presented in scientific sessions and will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT01933581: Pre-results.

The Role of Virtual Histology Intravascular Ultrasound in the Identification of Coronary Artery Plaque Vulnerability in Acute Coronary Syndromes.

Markers of coronary plaque vulnerability, such as a high lipid burden, increased inflammatory activity, and a thin fibrous cap, have been identified in histological studies. In vivo, grayscale intravascular ultrasound (IVUS) provides more in-depth information on coronary artery plaque burden than conventional angiography but is unable to accurately distinguish between noncalcific tissue types within the plaque. An analysis of IVUS radiofrequency backscatter based on spectral pattern recognition, such as virtual histology IVUS, allows detailed scrutiny of plaque composition and classification of coronary lesions. This review discusses the virtual histology IVUS technology and its accuracy in identifying vulnerable plaque features, focusing on its use in predicting patient outcomes after acute coronary syndrome, and its limitations in clinical practice.

Endothelial dysfunction and coronary artery disease: a state of the art review.

Atherosclerotic coronary artery disease (CAD) is a major cause of morbidity and mortality in the developed world. Endothelial dysfunction plays an important role in the development of atherosclerosis and predicts cardiovascular (CV) outcomes independent of conventional CV risk factors. In recent years, there have been tremendous improvements in the pharmacological prevention and management of CAD. In this review, the pathophysiology of endothelial dysfunction in relation to CAD is discussed and various techniques of invasive and noninvasive assessments of peripheral and coronary endothelial function described. In addition, evidence for the association of endothelial dysfunction and CV outcomes has been examined and finally the role of therapeutic interventions in endothelial dysfunction has been discussed.

Acute coronary syndrome among older patients: a review.

Ischemic heart disease is the leading cause of mortality worldwide. Due to advances in medicine in the past few decades, life expectancy has increased resulting in an aging population in developed and developing countries. Acute coronary syndrome causes greater morbidity and mortality in this group of older patients, which appears to be due to age-related comorbidities. This review examines the incidence and prevalence of acute coronary syndrome among older patients, examines current treatment strategies, and evaluates the predictors of adverse outcomes. In particular, the impact of frailty on outcomes and the need for frailty assessment in developing future research and management strategies among older patients are discussed.

Association of aging, arterial stiffness, and cardiovascular disease: a review.

Coronary heart disease (CHD) is the leading cause of morbidity and mortality in the western world. Primary and secondary prevention strategies have improved tremendously. Conventional risk factors are identified and treated with intensive pharmacotherapy. Despite these measures, the incidence of CHD is on the rise in developed countries. Arterial stiffness has been identified as an independent risk factor for the development of CHD, both in the general population and in those with established CHD. This review examines the association of arterial stiffness with cardiovascular disease.

High-throughput 13-parameter immunophenotyping identifies shifts in the circulating T-cell compartment following reperfusion in patients with acute myocardial infarction.

RATIONALE: With the advent of primary PCI (PPCI), reperfusion is achieved in almost all patients presenting with acute myocardial infarction. However, despite multiple trials, reperfusion injury has not been successfully dealt with so far. In mouse models, CD4(+) T lymphocytes (T cells) have been shown to be crucial instigators of reperfusion injury. OBJECTIVE: Our goal was to investigate the role of CD4(+) T cells during myocardial reperfusion following PPCI by developing a protocol for high-throughput multiplexed flow cytometric analysis and multivariate flow clustering. METHODS AND RESULTS: 13-parameter immunophenotyping and hierarchical cluster analysis (HCA) identified a unique CD4(+)CD57(+) T-cell population in PPCI patients that reflected acute proliferation in the CD4(+) T-cell compartment. CD4(+)CCR7(+) T cells were specifically depleted from peripheral blood during the first 30 min of myocardial reperfusion after PPCI, suggesting a potential role for the chemokine receptor CCR7 in T-cell redistribution to either peripheral tissues or migration to the infarcted heart during ischemia/reperfusion following PPCI. CONCLUSIONS: High-throughput polychromatic flow cytometry and HCA are capable of objective, time and cost efficient assessment of the individual T-cell immune profile in different stages of coronary heart disease and have broad applications in clinical trials.