Atherosclerosis Residual Lipid Risk-Overview of Existing and Future Pharmacotherapies.

Patients with atherosclerotic disease remain at increased risk of future events despite receiving optimal medical treatment. This residual risk is widely heterogeneous, but lipoprotein particles and their content play a major role in determining future cardiovascular events. Beyond low-density lipoprotein cholesterol (LDL-c), other lipoprotein particles have not demonstrated similar contribution to the progression of atherosclerosis. Statins, ezetimibe, and more recently, proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors and bempedoic acid have confirmed the causal role of LDL-c in the development of atherosclerosis. Data on high-density lipoprotein cholesterol (HDL-c) suggested a possible causal role for atherosclerosis; nonetheless, HDL-c-raising treatments, including cholesteryl-ester transfer protein (CETP) inhibitors and niacin, failed to confirm this relationship. On the other hand, mendelian randomisation revealed that triglycerides are more implicated in the development of atherosclerosis. Although the use of highly purified eicosapentaenoic acid (EPA) was associated with a reduction in the risk of adverse cardiovascular events, this beneficial effect did not correlate with the reduction in triglycerides level and has not been consistent across large phase 3 trials. Moreover, other triglyceride-lowering treatments, such as fibrates, were not associated with a reduction in future cardiovascular risk. Studies assessing agents targeting angiopoietin-like 3 (lipoprotein lipase inhibitor) and apolipoprotein C3 antisense will add further insights into the role of triglycerides in atherosclerosis. Emerging lipid markers such as lipoprotein (a) and cholesterol efflux capacity may have a direct role in the progression of atherosclerosis. Targeting these biomarkers may provide incremental benefits in reducing cardiovascular risk when added to optimal medical treatment. This Review aims to assess available therapies for current lipid biomarkers and provide mechanistic insight into their potential role in reducing future cardiovascular risk.

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 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.

Positive Predictive Value of Computerized Tomography Coronary Angiography versus Computerized Tomography Fractional Flow Reserve in a Real-world Population.

Background: Computed Tomography coronary angiography and fractional flow reserve (CTCA and CT-FFR) are noninvasive diagnostic tools for the detection of flow-limiting coronary artery stenoses. Although their negative predictive values are well established, there is a concern that the high sensitivity of these tests may lead to overestimation of coronary artery disease (CAD) and unnecessary invasive coronary angiography (ICA). We compared the positive predictive value (PPV) of CT-FFR with computerized tomography coronary angiography (CTCA) against the gold standard of ICA in different real-world patient groups. Methods: A retrospective analysis of 477 patients referred for CTCA or CT-FFR for investigation of possible coronary ischemia. Patients were excluded if the image quality was poor or inconclusive. Patient-based PPV was calculated to detect or rule out significant CAD, defined as more than 70% stenosis on ICA. A sub-analysis of PPV by indication for the scan was also performed. Patients who underwent invasive nonhyperemic pressure wire measurements had their instant wave-free ratio or resting full-cycle ratio compared with their CT-FFR values. Results: In a patient-based analysis, the overall PPV was 59.3% for CTCA and 76.2% for CT-FFR. This increased to 81.0% and 86.7%, respectively, for patients with stable angina symptoms. In patients with atypical angina symptoms, CT-FFR considerably outperformed CTCA with a PPV of 61.3% vs. 37.5%. There was not a linear relationship between invasive pressure wire measurement and CT-FFR value (r = 0.23, P = 0.265). Conclusion: The PPV of CTCA and CT-FFR is lower in the real world than in previously published trials, partly due to the heterogeneity of indication for the scan. However, in patients with typical angina symptoms, both are reliable diagnostic tools to determine the presence of clinically significant coronary stenoses. CT-FFR significantly outperforms CTCA in patients with more atypical symptoms and the targeted use of CT-FFR in this group may help to avoid unnecessary invasive procedures.

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.

Novel diagnostic approaches and management of coronary microvascular dysfunction.

The mechanism underlying ischaemic heart disease (IHD) has been primarily attributed to obstructive coronary artery disease (CAD). However, non-obstructive coronary arteries are identified in >50% of patients undergoing elective coronary angiography, recently leading to growing interest in the investigation and management of angina/ischaemia with non-obstructive coronary arteries (ANOCA/INOCA). INOCA is an umbrella term encompassing a multiple spectrum of possible pathogenetic entities, including coronary vasomotor disorders which consist of two major endotypes: coronary microvascular dysfunction (CMD) and vasospastic angina. Both conditions can coexist and be associated with concomitant obstructive CAD. Particularly, CMD refers to myocardial ischaemia due to reduced vasodilatory capacity of coronary microcirculation secondary to structural remodelling or impaired resting microvascular tone (functional) or a combination of both. CMD is not a benign condition and is more prevalent in women presenting with chronic coronary syndrome compared to men. In this setting, an impaired coronary flow reserve has been associated with increased risk of major adverse cardiovascular events. ANOCA/INOCA patients also experience impaired quality of life and associated increased healthcare costs. Therefore, research in this scenario has led to better definition, classification, and prognostic stratification based on the underlying pathophysiological mechanisms. The development and validation of non-invasive imaging modalities, invasive coronary vasomotor function testing and angiography-derived indices provide a comprehensive characterisation of CMD. The present narrative review aims to summarise current data relating to the diagnostic approach to CMD and provides details on the sequence that therapeutic management should follow.

Cardiac output in patients with small annuli undergoing transcatheter aortic valve implantation with self-expanding versus balloon expandable valve (COPS-TAVI).

BACKGROUND: There is limited data on cardiac output in patients with small aortic annuli undergoing trans-catheter aortic valve implantation (TAVI) according to the implanted platform of balloon-expandable (BEV) compared to self-expanding valves (SEV). METHODS: This is a retrospective analysis of consecutive patients with severe aortic stenosis and small annuli who underwent successful TAVI. Cardiac output was measured using echocardiography within 4 weeks following TAVI. Data were recorded and analysed by an experienced operator who was not aware of the type of the implanted valve. RESULTS: 138 patients were included in the analysis, of whom 57 % underwent TAVI with BEV. Clinical and echocardiographic characteristics were comparable between the two platforms, except for more frequent previous cardiac surgery and smaller indexed aortic valve in the BEV group. There was no relationship between computed tomography-derived aortic annulus area and cardiac output post TAVI. When compared to patients who underwent TAVI with BEV, those with SEV had larger cardiac output [mean difference - 0.50 l/min, 95 % CI (-0.99, -0.01)] and cardiac index [mean difference - 0.20 l/min/m2, 95 % CI (-0.47, 0.07)], although the latter did not reach statistical significance. Unlike patients with small body surface area, in those with large body surface area both cardiac output and cardiac index were statistically larger in patients who underwent SEV compared to BEV. CONCLUSION: Cardiac output, as measured by echocardiography, was larger in patients with small annuli who underwent TAVI procedure with SEV compared to BEV. Such difference was more evident in patients with large body surface area.

Bicuspid Aortic Valve Disease: Classifications, Treatments, and Emerging Transcatheter Paradigms.

Bicuspid aortic valve (BAV) is a common congenital valvular malformation, which may lead to early aortic valve disease and bicuspid-associated aortopathy. A novel BAV classification system was recently proposed to coincide with transcatheter aortic valve replacement being increasingly considered in younger patients with symptomatic BAV, with good clinical results, yet without randomized trial evidence. Procedural technique, along with clinical outcomes, have considerably improved in BAV patients compared with tricuspid aortic stenosis patients undergoing transcatheter aortic valve replacement. The present review summarizes the novel BAV classification systems and examines contemporary surgical and transcatheter approaches.