Phenotyping coronary plaque by computed tomography in premature coronary artery disease.

AIMS: Premature coronary artery disease (CAD) is an aggressive disease with multiple recurrences mostly related to new coronary lesions. This study aimed to compare coronary plaque characteristics of individuals with premature CAD with those of incidental plaques found in matched individuals free of overt cardiovascular disease, using coronary computed tomography angiography (CCTA). METHODS AND RESULTS: Of 1552 consecutive individuals who underwent CCTA, 106 individuals with history of acute or stable obstructive CAD ≤45 years were matched by age, sex, smoking status, cardiovascular heredity, and dyslipidaemia with 106 controls. CCTA were analysed for Coronary Artery Disease Reporting and Data System score, plaque composition, and high-risk plaque (HRP) features, including spotty calcification, positive remodelling, low attenuation, and napkin-ring sign. The characteristics of 348 premature CAD plaques were compared with those of 167 incidental coronary plaques of matched controls. The prevalence of non-calcified plaques was higher among individuals with premature CAD (65.1 vs. 30.2%, P < 0.001), as well as spotty calcification (42.5 vs. 17.9%, P < 0.001), positive remodelling (41.5 vs. 9.4%, P < 0.001), low attenuation (24.5 vs. 3.8%, P < 0.001), and napkin-ring sign (1.9 vs. 0.0%). They exhibited an average of 2.2 (2.7) HRP, while the control group displayed 0.4 (0.8) HRP (P < 0.001). Within a median follow-up of 24 (16, 34) months, individuals with premature CAD and ischaemic recurrence (n = 24) had more HRP [4.3 (3.9)] than those without ischaemic recurrence [1.5 (1.9)], mostly non-calcified with low attenuation and positive remodelling. CONCLUSION: Coronary atherosclerosis in individuals with premature CAD is characterized by a high and predominant burden of non-calcified plaque and unusual high prevalence of HRP, contributing to disease progression with multiple recurrences. A comprehensive qualitative CCTA assessment of plaque characteristics may further risk stratify our patients, beyond cardiovascular risk factors.

Transcatheter Mitral Valve Replacement Using Transcatheter Aortic Valve or Dedicated Devices: Current Evidence and Future Prospects.

Transcatheter mitral valve replacement (TMVR) is a novel and evolving field dedicated to addressing the therapeutic challenges posed by patients at high surgical risk with mitral valve disease. TMVR can be categorized into two distinct fields based on the type of device and its specific indications: TMVR with transcatheter aortic valves (TAV) and TMVR with dedicated devices. Similar to aortic stenosis, TMVR with TAV requires a rigid support structure to secure the valve in place. As a result, it is indicated for patients with failing bioprothesis or surgical rings or mitral valve disease associated with severe mitral annular calcification (MAC), which furnishes the necessary foundation for valve anchoring. While TMVR with TAV has shown promising outcomes in valve-in-valve procedures, its effectiveness remains more contentious in valve-in-ring or valve-in-MAC procedures. Conversely, TMVR with dedicated devices seeks to address native mitral regurgitation, whether accompanied by MAC or not, providing an alternative to Transcatheter Edge-to-Edge Repair (TEER) when TEER is not feasible or expected to yield unsatisfactory results. This emerging field is gradually surmounting technical challenges, including anchoring a valve in a non-calcified annulus and transitioning from the transapical route to the transeptal approach. Numerous devices are presently undergoing clinical trials. This review aims to furnish an overview of the supporting evidence for TMVR using TAV in each specific indication (valve-in-valve, valve-in-ring, valve-in-MAC). Subsequently, we will discuss the anticipated benefits of TMVR with dedicated devices over TEER, summarize the characteristics and clinical results of TMVR systems currently under investigation, and outline future prospects in this field.

Bioprosthetic leaflet thrombosis and reduced leaflet motion after transcatheter aortic valve replacement: A systematic review and meta-analysis.

BACKGROUND: Leaflet thrombosis and reduced leaflet motion have become a concern with the expanding use of transcatheter aortic valve replacement in lower-risk patients. AIMS: To assess the proportions, predictors and clinical impact of leaflet thrombosis and reduced leaflet motion after transcatheter aortic valve replacement. METHODS: We performed a meta-analysis of studies assessing the proportions of and/or clinical outcomes according to the presence of leaflet thrombosis after transcatheter aortic valve replacement identified with computed tomography and/or echocardiography. RESULTS: Fifty-three studies, representing 25,258 patients undergoing transcatheter aortic valve replacement, were considered. The proportion of leaflet thrombosis was 5.2% overall, and was higher in computed tomography versus echocardiography (16.4% vs. 1.1%, respectively); reduced leaflet motion was identified in 11% of patients with four-dimensional computed tomography. Intra-annular bioprostheses were associated with a higher proportion of leaflet thrombosis, whereas chronic oral anticoagulation was protective for leaflet thrombosis in both computed tomography and echocardiographic studies (9.7% vs. 17.5%; relative risk [RR]: 0.51, 95% confidence interval [95% CI]: 0.37-0.71 and 0.9% vs. 2.7%; RR: 0.22, 95% CI: 0.06-0.79, respectively) and for reduced leaflet motion (2.5% vs. 12.4%; RR: 0.32, 95% CI: 0.13-0.76). Leaflet thrombosis was not associated with an increased risk of death, but with a higher risk of stroke in computed tomography studies (2.8% vs. 2.4%; RR: 1.63, 95% CI: 1.05-2.55), a difference more pronounced when considering reduced leaflet motion (3.5% vs. 1.7%; RR: 2.39, 95% CI: 0.63-8.34). CONCLUSIONS: The proportion of leaflet thrombosis is highly variable according to the screening approach, the type of valve and the use of oral anticoagulation. The occurrence of cerebral events is increased when leaflet thrombosis and/or reduced leaflet motion are diagnosed, but leaflet thrombosis has no impact on survival.

Side of motor symptom onset predicts sustained attention deficits and motor improvements after attention training in Parkinson's disease.

OBJECTIVE: Parkinson's disease (PD) side of motor symptom onset has been associated with distinct cognitive deficits; individuals with left-side onset (LPD) show more visuospatial impairments, whereas those with right-side onset (RPD) show more verbal impairments. Non-spatial attention is a critical cognitive ability associated with motor functioning that is right hemisphere lateralized but has not been characterized with regard to PD side of onset. We compared individuals with LPD and RPD on non-spatial attention tasks and examined differential responses to a 4-week sustained attention training program. METHOD: Participants included 9 with LPD and 12 with RPD, who performed both brief and extended go/no-go continuous performance tasks and an attentional blink task. Participants also engaged in an at-home sustained attention training program, Tonic and Phasic Alertness Training (TAPAT), 5 days/week for 4 weeks. We assessed cognitive and motor symptoms before and after training, and after a 4-week no-contact period. RESULTS: At baseline, participants with LPD exhibited worse performance than those with RPD on the extended continuous performance task, indicating specific deficits in sustaining attention. Poorer attention was associated with worse clinical motor scores. Notably, side of onset had a significant effect on clinical motor changes after sustained attention training, with only LPD participants improving after training, and 4/9 showing clinically meaningful improvements. CONCLUSIONS: Compared to RPD, participants with LPD had poorer sustained attention pre-training and were more likely to improve on clinical motor functioning after sustained attention training. These findings support mechanistic differences between LPD and RPD and suggest potential differential treatment approaches.

Antithrombotic therapy and cardiovascular outcomes after transcatheter aortic valve implantation in patients without indications for chronic oral anticoagulation: a systematic review and network meta-analysis of randomized controlled trials.

AIMS: As the antithrombotic regimen that may best prevent ischaemic complications along with the lowest bleeding risk offset following transcatheter aortic valve implantation (TAVI) remains unclear, we aimed to compare the safety and efficacy of antithrombotic regimens in patients without having an indication for chronic oral anticoagulation. METHODS AND RESULTS: We conducted a PROSPERO-registered (CRD42021247924) systematic review and network meta-analysis of randomized controlled trials evaluating post-TAVI antithrombotic regimens up to April 2022. We estimated the relative risk (RR) and 95% confidence intervals (95% CIs) using a random-effects model in a frequentist pairwise and network metanalytic approach. We included seven studies comprising 4006 patients with a mean weighted follow-up of 12.9 months. Risk of all-cause death was significantly reduced with dual antiplatelet therapy (DAPT) compared with low-dose rivaroxaban + 3-month single antiplatelet therapy (SAPT) (RR 0.60, 95% CI 0.41-0.88), while no significant reduction was observed with SAPT vs. DAPT (RR 1.02, 95% CI 0.67-1.58) and SAPT and DAPT compared with apixaban or edoxaban (RR 0.60, 95% CI 0.32-1.14 and RR 0.59, 95% CI 0.34-1.02, respectively). SAPT was associated with a significant reduction of life-threatening, disabling, or major bleeding compared with DAPT (RR 0.45, 95% CI 0.29-0.70), apixaban or edoxaban alone (RR 0.45, 95% CI 0.25-0.79), and low-dose rivaroxaban + 3-month SAPT (RR 0.30, 95% CI 0.16-0.57). There were no differences between the various regimens with respect to myocardial infarction, stroke, or systemic embolism. CONCLUSION: Following TAVI in patients without an indication for chronic oral anticoagulant, SAPT more than halved the risk of bleeding compared with DAPT and direct oral anticoagulant-based regimens without significant ischaemic offset.

Prevention and treatment of premature ischaemic heart disease with European Society of Cardiology Guidelines.

OBJECTIVE: To determine if the changes in the European Society Cardiology/European Atherosclerotic Society (ESC/EAS) guidelines improved the identification for primary prevention therapy in young adults at risk of a premature myocardial infarction. METHODS: Patients admitted for a first ST-segment elevation myocardial infarction (STEMI) in the ePARIS registry (n=2757) between 2010 and 2018 were classified by age: <55, 55-65 and >65 years old. Using Systematic Coronary Risk Estimation 2, we evaluated whether patients would have been detected and treated with primary prevention statins before their first STEMI based on the 2021 EAS/ESC guidelines versus 2019 and 2016 guidelines. Eligibility for intensive proprotein convertase subtilisin/kexin type 9 (PCSK9i) in secondary prevention was also assessed. RESULTS: Following 2021 ESC guidelines, 62.5% of individuals aged <55 years old would have been eligible for statins before their first STEMI, similarly to older age categories. In comparison, only 17% and 18% of young individuals would have been eligible for primary prevention statins prior to their first STEMI with 2016 and 2019 guidelines, compared with group 55-65 years (41% and 35%) and >65 years old (19% and 72%), p<0.01. After their first STEMI, 25% of patients <55 years would be eligible for PCSK9i, compared with 23.2% and 15% in patients aged 55-65 years and >65 years. CONCLUSIONS: The 2021 ESC guidelines allowed a much better detection of young individuals before their first STEMI than prior ESC guidelines. In secondary prevention, most of young individuals did not reach low-density lipoprotein cholesterol levels recommended, but only one quarter would be eligible for PCSK9i.

Beta-blocker prescription and outcomes in uncomplicated acute myocardial infarction: Insight from the ePARIS registry.

BACKGROUND: Systematic prescription of beta-blockers after myocardial infarction remains an open question in the era of revascularization, especially for patients with uncomplicated myocardial infarction. OBJECTIVE: To evaluate in a real-life registry the proportion of patients with uncomplicated myocardial infarction (preserved left ventricular ejection fraction and no cardiovascular event within the first 6 months), and to report their characteristics, outcomes and beta-blocker use. METHODS: We included 1887 consecutive patients with ST-segment elevation myocardial infarction from the prospective ePARIS registry. Patients were divided into three groups: the "uncomplicated myocardial infarction" group (n=1060), defined by a left ventricular ejection fraction ≥ 40% and a 6-month period free from cardiovascular events; the "complicated myocardial infarction" group (n=366), defined by a left ventricular ejection fraction ≥ 40% and a recurrent cardiovascular event in the first 6 months; and the "left ventricular dysfunction" group (n=461), defined by a left ventricular ejection fraction<40%. RESULTS: During a median follow-up of 2.7 years (interquartile range 1.0-4.9 years), the "uncomplicated myocardial infarction" group was at low mortality risk compared with the "complicated myocardial infarction" group (hazard ratio 0.38, 95% confidence interval 0.25-0.58; P<0.01) and the "left ventricular dysfunction" group (hazard ratio 0.22, 95% confidence interval 0.15-0.32; P<0.01). Beta-blockers were prescribed at discharge predominantly in the "uncomplicated myocardial infarction" group (93%) compared with 87% in the "complicated myocardial infarction" group and 81% in the "left ventricular dysfunction" group. CONCLUSIONS: Beta-blockers are less prescribed in patients who may need them the most. The benefit of beta-blockers-largely prescribed in lower-risk patients-remains to be shown beyond the first 6 months for these patients with no left ventricular dysfunction and no recurrent events.

Apixaban vs. standard of care after transcatheter aortic valve implantation: the ATLANTIS trial.

AIMS: The respective roles of oral anticoagulation or antiplatelet therapy following transcatheter aortic valve implantation (TAVI) remain debated. ATLANTIS is an international, randomized, open-label, superiority trial comparing apixaban to the standard of care. METHODS AND RESULTS: After successful TAVI, 1500 patients were randomized (1:1) to receive apixaban 5 mg (2.5 mg if impaired renal function or concomitant antiplatelet therapy) (n = 749) twice daily, or standard of care (n = 751). Randomization was stratified by the need for chronic anticoagulation therapy. Standard-of-care patients received a vitamin K antagonist (VKA) (Stratum 1) or antiplatelet therapy (Stratum 2) if there was an indication for anticoagulation or not, respectively. The primary endpoint was the composite of death, myocardial infarction, stroke or transient ischaemic attack, systemic embolism, intracardiac or bioprosthesis thrombosis, deep vein thrombosis or pulmonary embolism, and life-threatening, disabling, or major bleeding over 1-year follow-up. The primary safety endpoint was major, disabling, or life-threatening bleeding. The primary outcome occurred in 138 (18.4%) and 151 (20.1%) patients receiving apixaban or standard of care, respectively [hazard ratio (HR) 0.92; 95% confidence interval (CI) 0.73-1.16] and there was no evidence of interaction between treatment and stratum (Pinteraction = 0.57). The primary safety endpoint was similar in both groups (HR 1.02; 95% CI 0.72-1.44). In Stratum 1 (n = 451), an exploratory analysis showed no difference for all endpoints between apixaban and VKA. In Stratum 2 (n = 1049), the primary outcome and primary safety endpoint did not differ, but obstructive valve thrombosis was reduced with apixaban vs. antiplatelet therapy (HR 0.19; 95% CI 0.08-0.46), while a signal of higher non-cardiovascular mortality was observed with apixaban. CONCLUSION: After TAVI, apixaban was not superior to the standard of care, irrespective of an indication for oral anticoagulation.

ESC/EAS guidelines for the detection, prevention, and treatment of individuals at risk of a first myocardial infarction: effect of 5 years of updates and the new SCORE2.

AIMS: The European Society of Cardiology (ESC) has released three consecutive guidelines within 5 years addressing cardiovascular prevention, risk scores, and cholesterol treatment. This study aims to evaluate whether the 2021 ESC guidelines improved the eligibility of individuals for primary prevention statin therapy before their first ST-segment elevation myocardial infarction (STEMI), and for intensive lipid-lowering treatments in secondary prevention. METHODS AND RESULTS: The cardiovascular risk category of 2757 consecutive individuals admitted for a first STEMI was evaluated to assess whether they would have been eligible for primary prevention statins according to 2021 vs. 2019 and 2016 ESC guidelines. Eligibility for intensive lipid-lowering therapy in secondary prevention was assessed according to the real-life follow-up low-density lipoprotein cholesterol (LDL-C) and the expected follow-up LDL-C. More individuals would have been eligible for primary prevention statins according to 2021 and 2019 vs. 2016 guidelines (61.8% vs. 38.7% vs. 23.6%, P < 0.01), a finding observed in both men (62.3% vs. 35.0% vs. 24.9%, P < 0.01) and women (60.2% vs. 50.7% vs. 19.3%, P = 0.18). Only 27% of individuals reached the LDL-C objective of 55 mg/L in secondary prevention: using the ESC stepwise approach, 61.7% were eligible for higher doses of statins, 26.2% for ezetimibe, and 12.1% for a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor (PCSK9i). Based on expected LDL-C reductions, eligibility for a PCSK9i in secondary prevention was greater with 2021 vs. 2016 guidelines (44.5% vs. 22.5%, P < 0.01). CONCLUSION: The 2021 ESC guidelines improved the detection and treatment of individuals at risk for a first myocardial infarction. In secondary prevention, 70% of patients kept LDL-C levels above 55 mg/dL: increasing the statin dose and adding ezetimibe were the most frequently recommended therapeutic actions.

Fractional Flow Reserve to Guide Treatment of Patients With Multivessel Coronary Artery Disease.

BACKGROUND: There is limited evidence that fractional flow reserve (FFR) is effective in guiding therapeutic strategy in multivessel coronary artery disease (CAD) beyond prespecified percutaneous coronary intervention or coronary graft surgery candidates. OBJECTIVES: The FUTURE (FUnctional Testing Underlying coronary REvascularization) trial aimed to evaluate whether a treatment strategy based on FFR was superior to a traditional strategy without FFR in the treatment of multivessel CAD. METHODS: The FUTURE trial is a prospective, randomized, open-label superiority trial. Multivessel CAD candidates were randomly assigned (1:1) to treatment strategy based on FFR in all stenotic (≥50%) coronary arteries or to a traditional strategy without FFR. In the FFR group, revascularization (percutaneous coronary intervention or surgery) was indicated for FFR ≤0.80 lesions. The primary endpoint was a composite of major adverse cardiac or cerebrovascular events at 1 year. RESULTS: The trial was stopped prematurely by the data safety and monitoring board after a safety analysis and 927 patients were enrolled. At 1-year follow-up, by intention to treat, there were no significant differences in major adverse cardiac or cerebrovascular events rates between groups (14.6% in the FFR group vs 14.4% in the control group; hazard ratio: 0.97; 95% confidence interval: 0.69-1.36; P = 0.85). The difference in all-cause mortality was nonsignificant, 3.7% in the FFR group versus 1.5% in the control group (hazard ratio: 2.34; 95% confidence interval: 0.97-5.18; P = 0.06), and this was confirmed with a 24 months' extended follow-up. FFR significantly reduced the proportion of revascularized patients, with more patients referred to exclusively medical treatment (P = 0.02). CONCLUSIONS: In patients with multivessel CAD, we did not find evidence that an FFR-guided treatment strategy reduced the risk of ischemic cardiovascular events or death at 1-year follow-up. (Functional Testing Underlying Coronary Revascularisation; NCT01881555).

Predictive Value of the Residual SYNTAX Score in Patients With Cardiogenic Shock.

BACKGROUND: In hemodynamically stable patients, complete revascularization (CR) following percutaneous coronary intervention (PCI) is associated with a better prognosis in chronic and acute coronary syndromes. OBJECTIVES: This study sought to assess the extent, severity, and prognostic value of remaining coronary stenoses following PCI, by using the residual SYNTAX score (rSS), in patients with cardiogenic shock (CS) related to myocardial infarction (MI). METHODS: The CULPRIT-SHOCK (Culprit Lesion Only Percutaneous Coronary Intervention [PCI] Versus Multivessel PCI in Cardiogenic Shock) trial compared a multivessel PCI (MV-PCI) strategy with a culprit lesion-only PCI (CLO-PCI) strategy in patients with multivessel coronary artery disease who presented with MI-related CS. The rSS was assessed by a central core laboratory. The study group was divided in 4 subgroups according to tertiles of rSS of the participants, thereby isolating patients with an rSS of 0 (CR). The predictive value of rSS for the 30-day primary endpoint (mortality or severe renal failure) and for 30-day and 1-year mortality was assessed using multivariate logistic regression. RESULTS: Among the 587 patients with an rSS available, the median rSS was 9.0 (interquartile range: 3.0 to 17.0); 102 (17.4%), 100 (17.0%), 196 (33.4%), and 189 (32.2%) patients had rSS = 0, 0 < rSS ≤5, 5 < rSS ≤14, and rSS >14, respectively. CR was achieved in 75 (25.2%; 95% confidence interval [CI]: 20.3% to 30.5%) and 27 (9.3%; 95% CI: 6.2% to 13.3%) of patients treated using the MV-PCI and CLO-PCI strategies, respectively. After multiple adjustments, rSS was independently associated with 30-day mortality (adjusted odds ratio per 10 units: 1.49; 95% CI: 1.11 to 2.01) and 1-year mortality (adjusted odds ratio per 10 units: 1.52; 95% CI: 1.11 to 2.07). CONCLUSIONS: Among patients with multivessel disease and MI-related CS, CR is achieved only in one-fourth of the patients treated using an MV-PCI strategy. and the residual SYNTAX score is independently associated with early and late mortality.