Bleeding Risk in Patients Receiving Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: There is a potential concern about increased bleeding risk in patients receiving omega-3 polyunsaturated fatty acids (PUFAs). The aims of this study-level meta-analysis were to determine the risk of bleeding and to assess whether this relationship is linked to the received dose of omega-3 PUFAs or the background use of antiplatelet treatment. METHODS AND RESULTS: Electronic databases were searched through May 2023 to identify randomized clinical trials of patients receiving omega-3 PUFAs. Overall bleeding events, including fatal and central nervous system events, were identified and compared with those of a control group. A total of 120 643 patients from 11 randomized clinical trials were included. There was no difference in the pooled meta-analytic events of bleeding among patients receiving omega-3 PUFAs and those in the control group (rate ratio [RR], 1.09 [95% CI, 0.91-1.31]; P=0.34). Likewise, the incidence of hemorrhagic stroke, intracranial bleeding, and gastrointestinal bleeding were similar. A prespecified analysis was performed in patients receiving high-dose purified eicosapentaenoic acid (EPA), which demonstrated a 50% increase in the relative risk of bleeding but only a modest increase in the absolute risk of bleeding (0.6%) when compared with placebo. Bleeding risk was associated with the dose of EPA (risk difference, 0.24 [95% CI, 0.05-0.43]; P=0.02) but not the background use of antiplatelet therapy (risk difference, -0.01 [95% CI, -0.02 to 0]; P=0.056). CONCLUSIONS: Omega-3 PUFAs were not associated with increased bleeding risk. Patients receiving high-dose purified EPA may incur additional bleeding risk, although its clinical significance is very modest.

The role of gender in resting full-cycle ratio (RFR) guided coronary revascularization.

BACKGROUND: Gender-based differences in clinical outcomes of patients undergoing fractional flow reserved (FFR) guided coronary revascularization is well documented. This study aimed to compare resting full-cycle ratio (RFR) values between men and women and whether this translated into difference in clinical outcomes in patients who underwent RFR-guided coronary revascularization. METHODS: This was a retrospective single-centre study of consecutive patients who underwent RFR-guided revascularization for coronary lesions with intermediate degree of stenosis. The primary endpoint was a composite of all-cause mortality, myocardial infarction (MI), unplanned revascularization, and unstable angina requiring hospital admission at one year. RESULTS: In 373 consecutive patients (510 lesions, 26% women) there was no statistically significant difference in RFR value between men and women (0.90 ± 10 versus 0.90 ± 11, P = 0.95). There was no statistically significant difference between men and women in the primary endpoint, even after adjustment to the imbalance between the two groups [3.7% vs. 3.0%; HR 1.43, 95% CI (0.46 to 4.43), P = 0.54]; or its individual components of death (1.1% vs 0.8%, P = 0.76), MI (1.9% vs 0.8%, P = 0.38) or unplanned revascularization, including unstable angina admissions (2.6% vs 2.3%, P = 0.82). The comparable clinical outcomes were consistent across all different subgroups, including clinical presentation, diabetes status, left ventricle systolic function, kidney function, and the interrogated coronary artery. CONCLUSION: Our study suggests no significant gender-based difference in the value of RFR or 1-year clinical outcomes in patients undergoing resting physiology guided coronary revascularization.

The Use of Thrombectomy during Primary Percutaneous Coronary Intervention: Resurrecting an Old Concept in Contemporary Practice.

Optimal myocardial reperfusion during primary percutaneous coronary intervention (pPCI) is increasingly recognized to be beyond restoring epicardial coronary flow. Both invasive and non-invasive tools have highlighted the limitation of using this metric, and more efforts are focused towards achieving optimal reperfusion at the level of the microcirculation. Recent data highlighted the close relationship between thrombus burden and impaired microcirculation in patients presenting with ST-segment elevation myocardial infarction (STEMI). Moreover, distal embolization was an independent predictor of mortality in patients with STEMI. Likewise, the development of no-reflow phenomenon has been directly linked with worse clinical outcomes. Adjunctive thrombus aspiration during pPCI is intuitively intended to remove atherothrombotic material to mitigate the risk of distal embolization and the no-reflow phenomenon (NRP). However, prior trials on the use of thrombectomy during pPCI did not support its routine use, with comparable clinical endpoints to patients who underwent PCI alone. This article aims to review the existing literature highlighting the limitation on the use of thrombectomy and provide future insights into trials investigating the role of thrombectomy in contemporary pPCI.

Acute myocardial infarction associated with multiple giant coronary artery aneurysms: a management dilemma.

A 77-year-old man presented with an acute inferior ST-segment elevation myocardial infarction.

Microvascular Obstruction in Acute Myocardial Infarction, a Potential Therapeutic Target.

Microvascular obstruction (MVO) is a recognised phenomenon following mechanical reperfusion in patients presenting with ST-segment elevation myocardial infarction (STEMI). Invasive and non-invasive modalities to detect and measure the extent of MVO vary in their accuracy, suggesting that this phenomenon may reflect a spectrum of pathophysiological changes at the level of coronary microcirculation. The importance of detecting MVO lies in the observation that its presence adds incremental risk to patients following STEMI treatment. This increased risk is associated with adverse cardiac remodelling seen on cardiac imaging, increased infarct size, and worse patient outcomes. This review provides an outline of the pathophysiology, clinical implications, and prognosis of MVO in STEMI. It describes historic and novel pharmacological and non-pharmacological therapies to address this phenomenon in conjunction with primary PCI.

Activation of telomerase by TA-65 enhances immunity and reduces inflammation post myocardial infarction.

Myocardial infarction (MI) accelerates immune ageing characterised by lymphopenia, expansion of terminally differentiated CD8+ T-lymphocytes (CD8+ TEMRA) and inflammation. Pre-clinical data showed that TA-65, an oral telomerase activator, reduced immune ageing and inflammation after MI. We conducted a double blinded randomised controlled pilot trial evaluating the use of TA-65 to reduce immune cell ageing in patients following MI. Ninety MI patients aged over 65 years were randomised to either TA-65 (16 mg daily) or placebo for 12 months. Peripheral blood leucocytes were analysed by flow cytometry. The pre-defined primary endpoint was the proportion of CD8+ T-lymphocytes which were CD8+ TEMRA after 12 months. Secondary outcomes included high-sensitivity C-reactive protein (hsCRP) levels. Median age of participants was 71 years. Proportions of CD8+ TEMRA did not differ after 12 months between treatment groups. There was a significant increase in mean total lymphocyte count in the TA-65 group after 12 months (estimated treatment effect: + 285 cells/µl (95% CI: 117-452 cells/ µ l, p < 0.004), driven by significant increases from baseline in CD3+, CD4+, and CD8+ T-lymphocytes, B-lymphocytes and natural killer cells. No increase in lymphocyte populations was seen in the placebo group. At 12 months, hsCRP was 62% lower in the TA-65 group compared to placebo (1.1 vs. 2.9 mg/L). Patients in the TA-65 arm experienced significantly fewer adverse events (130 vs. 185, p = 0.002). TA-65 did not alter CD8+ TEMRA but increased all major lymphocyte subsets and reduced hsCRP in elderly patients with MI after 12 months.

Very Early Discharge After Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction: Mortality Outcomes at Six Months.

BACKGROUND: Current guidelines recommend that low risk patients presenting with ST-segment elevation myocardial infarction (STEMI) and undergoing uncomplicated primary percutaneous coronary intervention (PPCI) can be discharged home in 48-72 h. We report the safety of early discharge in STEMI patients undergoing uncomplicated PPCI after 24-h stay in-hospital. METHODS: We performed a retrospective analysis of prospectively collected data of consecutive patients presenting with STEMI between January 2014 and December 2020. One- and 6-month mortality rates were compared between patients who underwent next day (early discharge group) and two days in-hospital stay (standard discharge group). RESULTS: Of 6119 STEMI patients, 4033 were included in the analysis, of whom 1674 (42 %) underwent early discharge. Patients in the early discharge group were younger, more likely to be male, and had a lower peak troponin. Both groups had similar ischemia- and door-to-balloon time, but anterior STEMI were less frequent in the early discharge group. The 1- and 6-month mortality rate for the whole cohort was 0.6 % and 1.3 %, respectively. After adjustment, there were no significant differences in the 1-month [HR 0.54; 95 % CI (0.20 to 1.47), P = 0.23] and 6-month mortality [HR 0.73; 95 % CI (0.38 to 1.41), P = 0.35] between early and standard discharge groups. Age, admission heart rate and chronic obstructive lung disease were identified as independent predictors of 6-month mortality in patients who underwent early discharge strategy. CONCLUSION: Our data confirms safety of next day discharge of patients presenting with STEMI after successful PPCI and uncomplicated post-procedural course.

Isolated Septal Artery Infarction in a Cocaine User.

Septal branches arising from the left anterior descending coronary artery supply the anterior interventricular septum in unison. In this unusual presentation of cocaine heart disease, occlusion of a single dominant septal perforator caused a large septal myocardial infarction, resulting in significant left ventricular impairment.

Combined Rotational Atherectomy and Intravascular Lithotripsy to Treat a Calcified Vein Graft Stenosis.

Percutaneous coronary intervention to treat saphenous vein graft stenosis can be complicated by significant lesion and vessel wall calcification. We describe the first case of combined rotational atherectomy and intravascular lithotripsy to treat a severely calcified vein graft stenosis.

Anterograde Crossing of a Bicuspid Aortic Valve Through Transseptal Access to Facilitate Transcatheter Aortic Valve Implantation.

Transcatheter aortic valve implantation (TAVI) for bicuspid aortic valve stenosis can pose several technical challenges including difficult valve crossing. We report the case of a 77-year-old woman undergoing transfemoral TAVI for symptomatic severe bicuspid aortic stenosis. It proved impossible to cross the bicuspid aortic valve retrogradely despite the use of multiple catheters and wires and attempts by two interventional cardiologists. We describe a novel approach to antegrade crossing, through a transseptal access, to permit retrograde implant of prosthesis.

Telomerase Activation to Reverse Immunosenescence in Elderly Patients With Acute Coronary Syndrome: Protocol for a Randomized Pilot Trial.

BACKGROUND: Inflammation plays a key role in the pathophysiology of coronary heart disease (CHD) and its acute manifestation, acute coronary syndrome (ACS). Aging is associated with a decline of the immune system, a process known as immunosenescence. This is characterized by an increase in highly proinflammatory T cells that are involved in CHD progression, plaque destabilization, and myocardial ischemia-reperfusion injury. Telomere dysfunction has been implicated in immunosenescence of T lymphocytes. Telomerase is the enzyme responsible for maintaining telomeres during cell divisions. It has a protective effect on cells under oxidative stress and helps regulate flow-mediated dilation in microvasculature. OBJECTIVE: The TACTIC (Telomerase ACTivator to reverse Immunosenescence in Acute Coronary Syndrome) trial will investigate whether a telomerase activator, TA-65MD, can reduce the proportion of senescent T cells in patients with ACS with confirmed CHD. It will also assess the effect of TA-65MD on decreasing telomere shortening, reducing oxidative stress, and improving endothelial function. METHODS: The study was designed as a single-center, randomized, double-blind, parallel-group, placebo-controlled phase II trial. Recruitment started in January 2019. A total of 90 patients, aged 65 years or older, with treated ACS who have had CHD confirmed by angiography will be enrolled. They will be randomized to one of two groups: TA-65MD oral therapy (8 mg twice daily) or placebo taken for 12 months. The primary outcome is the effect on immunosenescence determined by a decrease in the proportion of CD8+ TEMRA (T effector memory cells re-expressing CD45RA [CD45 expressing exon A]) cells at 12 months. Secondary outcomes include leukocyte telomere length, endothelial function, cardiac function as measured by echocardiography and NT-proBNP (N-terminal fragment of the prohormone brain-type natriuretic peptide), systemic inflammation, oxidative stress, and telomerase activity. RESULTS: The study received National Health Service (NHS) ethics approval on August 9, 2018; Medicines and Healthcare products Regulatory Agency approval on October 19, 2018; and NHS Health Research Authority approval on October 22, 2018. The trial began recruiting participants in January 2019 and completed recruitment in March 2020; the trial is due to report results in 2021. CONCLUSIONS: This pilot trial in older patients with CHD will explore outcomes not previously investigated outside in vitro or preclinical models. The robust design ensures that bias has been minimized. Should the results indicate reduced frequency of immunosenescent CD8+ T cells as well as improvements in telomere length and endothelial function, we will plan a larger, multicenter trial in patients to determine if TA-65MD is beneficial in the treatment of CHD in elderly patients. TRIAL REGISTRATION: ISRCTN Registry ISRCTN16613292; http://www.isrctn.com/ISRCTN16613292 and European Union Drug Regulating Authorities Clinical Trials Database (EudraCT), European Union Clinical Trials Register 2017-002876-26; https://tinyurl.com/y4m2so8g. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/19456.

Percutaneous coronary intervention for left main stem disease: Impact of diabetes mellitus on mortality.

OBJECTIVES: We assessed the impact of diabetes mellitus (DM) on mortality after percutaneous coronary intervention (PCI) for left main stem (LMS) disease. Second, we compared mortality outcomes between non-insulin treated (NITDM) and insulin treated diabetes (ITDM) in different clinical settings. BACKGROUND: There is a paucity of "real world" outcomes data in diabetic patients undergoing LMS PCI. METHODS: We undertook a retrospective analysis of consecutive patients undergoing unprotected LMS PCI at 2 high volume tertiary centers. Diabetic status and clinical setting for PCI were recorded. The primary outcome measure was all-cause 30-day and long-term mortality (up to 36 months) post index PCI. RESULTS: Between 2003 and 2017, 2,675 patients undergoing index LMS PCI were analyzed. Of those, 77.1% were non-DM, 15.8% NITDM, and 7.1% ITDM. Overall, DM status was not associated with higher 30-day mortality (OR 1.39, 95% CI 0.89-2.16, p = .15). During a median follow-up of 36 months, there was a borderline statistical association of DM with long-term mortality in all PCI settings (HR 1.31, 95% CI 1.00-1.71, p = .05). Compared to non-DM, ITDM but not NITDM was associated with short- and long-term mortality in all clinical presentations. CONCLUSIONS: Overall, DM did not impact on 30-day mortality and had only a borderline statistical association with long-term mortality. It did not have an influence on mortality in non-emergency LMS PCI. The impact of DM on mortality outcomes following LMS PCI was only significant in the insulin treated patients.

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.

Outcomes following primary percutaneous coronary intervention in the setting of cardiac arrest: a registry database study.

BACKGROUND: The mortality rate among patients undergoing primary percutaneous coronary intervention (PPCI) in the setting of cardiac arrest (CA) and whether the location where the patient sustains CA influences the outcome is not known in the contemporary era. METHODS: Prospectively collected data at a tertiary cardiac centre on all patients undergoing PPCI for ST elevation myocardial infarction (STEMI) in the setting of CA was analysed. RESULTS: In total, 484/4118 (11.8%) patients sustained CA during the study period. Of these, 91/484 (18.8%) sustained CA prior to ambulance arrival, the remainder occurred either after ambulance arrival or in hospital. The overall in-hospital mortality was 20.5% in this cohort. Those sustaining CA before ambulance arrival experienced the highest unadjusted mortality compared to those that had CA after ambulance arrival, in hospital and in the catheterisation laboratory (29.7% versus 12.0%, 16.1% and 23.8% respectively, p=0.03). Multiple logistic regression analysis showed that the following parameters are independent predictors of in-hospital mortality: age (odds ratio (OR) for each year increment of age 1.05; 95% confidence interval (CI) 1.02-1.08, p=0.0009); female gender (OR 2.42; 95% CI 1.17-4.99, p=0.0173); previous PCI (OR 7.59; 95% CI 1.72-33.53, p=0.0075); asystole/ electromechanical dissociation (EMD) (OR 13.43; 95% CI 5.34-33.80, p<0.0001); and patient location at arrest (OR 5.77 for before ambulance arrival; 95% CI 2.55-13.07, p<0.0001). CONCLUSIONS: In conclusion, in-hospital mortality remains high among patients undergoing PPCI in the context of CA, particularly among those that arrest prior to ambulance arrival.

Physical activity in the management of patients with coronary artery disease: a review.

Cardiovascular diseases remain the leading cause of death in the Western world despite advances in therapeutics and interventions. The prescription of physical activity is a key component of cardiac rehabilitation following myocardial infarction. This review aims to outline the impact of physical activity in particular patient cohorts with coronary artery disease. The current understanding of the mechanisms involved in atherosclerosis, plaque rupture and thrombosis, and how these can be modified by physical activity, are also discussed. There is the potential for future research to investigate the clinical and mechanistic effects of different exercise types, intensities, duration, and frequencies in patients hospitalized for coronary artery disease.

Vitamin D deficiency and coronary artery disease: a review of the evidence.

Coronary artery disease remains the leading cause of death in developed countries despite significant progress in primary prevention and treatment strategies. Older patients are at particularly high risk of poor outcomes following acute coronary syndrome and impaired nutrition, including low vitamin D levels, may play a role. The extraskeletal effects of vitamin D, in particular, its role in maintaining a healthy cardiovascular system are receiving increased attention. Longitudinal studies have demonstrated increased cardiovascular mortality and morbidity associated with vitamin D deficiency. Low vitamin D levels have been linked to inflammation, higher coronary artery calcium scores, impaired endothelial function and increased vascular stiffness. However, so far, few randomized controlled trials have investigated the potential benefits of vitamin D supplementation in preventing cardiovascular events, and most available trials have tested low doses of supplementation in relatively low-risk populations. Whether vitamin D supplementation will be beneficial among patients with coronary artery disease, including high risk older patients presenting with acute coronary syndrome, is unknown and warrants further investigation.

Gender comparisons in cardiogenic shock during ST elevation myocardial infarction treated by primary percutaneous coronary intervention.

Among patients hospitalized with acute myocardial infarction (AMI), cardiogenic shock (CS) is the leading cause of death, complicating up to 10% of admissions. Introduction of early revascularization strategies and mechanical ventricular support have seen short-term mortality associated with CS fall from 70% to 80% in the 1970s to approximately 50% to 60% in the 1990s. Previous studies reported a higher incidence of CS after AMI in women (11.6% vs 8.3%). The aims of this study were to determine hospital mortality outcomes and gender differences following primary percutaneous coronary intervention (PPCI) in the setting of CS. Data were collected prospectively among all patients undergoing PPCI for AMI at a large UK tertiary cardiac center between April 2008 and October 2011. A sample of 2,864 patients (women: 844 [29.5%]) underwent PPCI, of which 141 (4.9%) had a confirmed diagnosis of CS. Eighty-one of 2,019 [4.0%] male patients (mean age: 64.2 years) and 60 of 844 [7.1%]) female patients (mean age: 69.9 years) with CS underwent PPCI (p <0.001). The overall hospital mortality was 35.5% with no gender difference (male: 35.8% vs female: 35%, p >0.99). In conclusion, this analysis demonstrates that in the contemporary PPCI era, there is a reduction in the incidence of CS with reduced hospital mortality rates and no gender difference. The absence of a gender difference is remarkable because higher proportions of women presented with CS and were older than their male counterparts. Long-term follow-up data are required to determine if this difference is sustained.

Risk scores in acute coronary syndrome and percutaneous coronary intervention: a review.

Patients with acute coronary syndrome (ACS) need to be risk stratified to deliver the most appropriate therapy. The GRACE and TIMI risk scores have penetrated contemporary guidelines with the former most commonly used in clinical practice. However, ACS prediction models need to be re-evaluated in contemporary practice with evolving diagnostic and treatment options. Moreover, the increased availability of percutaneous coronary intervention (PCI) as a treatment option for ACS combined with an expanding case mix and emphasis on quality control have triggered the creation of PCI specific prognostic models. These allow clinicians and patients to have an understanding of expected outcomes following PCI by predicting outcomes in-hospital to 5 years following intervention. The aim of this review is to evaluate the most recognized and studied ACS/PCI risk models, focusing on their strengths and limitations, and to assess the need for more robust tools to predict outcomes in a period of constantly advancing technologies and changing patient demographics.