Persistence of residual shunt at 6 and 12 months after transoesophageal echocardiography-guided percutaneous closure of a patent foramen ovale for cryptogenic stroke.

BACKGROUND: Young patients suffering from cryptogenic stroke alongside a patent foramen ovale (PFO) are often considered for percutaneous device closure to reduce the risk of stroke recurrence. Residual right-to-left shunt after device closure may persist in approximately a quarter of the patients at 6 months, and some may close at a later time point. This study aimed to assess the prevalence and persistence of residual right-to-left shunt after percutaneous PFO closure. METHODS: Consecutive patients undergoing transoesophageal echocardiography-guided PFO closure for cryptogenic stroke between 2006 and 2021, with echocardiographic follow-up including contrast bubble study and Valsalva manoeuvre, were enrolled. Follow-up transthoracic echocardiography was performed at 6 months and repeated at 12 months in case of residual right-to-left shunt. Primary outcomes included the prevalence and grade of residual right-to-left shunt at 6 and 12 months after percutaneous PFO closure. RESULTS: 227 patients were included with a mean age of 43±11 years and 50.2% were women. At 6-month follow-up, 72.7% had no residual right-to-left shunt, 12.3% small residual right-to-left shunt, 6.6% moderate residual right-to-left shunt and 8.4% large residual right-to-left shunt. At 12-month follow-up, the presence of residual right-to-left shunt in all patients was 12.3%, of whom 6.6% had small residual right-to-left shunt, 2.6% had moderate residual right-to-left shunt and 3.1% had large residual right-to-left shunt. CONCLUSIONS: Residual right-to-left shunts are common at 6 months after percutaneous closure of PFO. However, the majority are small and two-thirds of residual right-to-left shunts achieve complete closure between 6 and 12 months.

Temporary omission of oral anticoagulation in atrial fibrillation patients undergoing percutaneous coronary intervention: rationale and design of the WOEST-3 randomised trial.

The optimal antithrombotic management of atrial fibrillation (AF) patients who require oral anticoagulation (OAC) undergoing percutaneous coronary intervention (PCI) remains unclear. Current guidelines recommend dual antithrombotic therapy (DAT; OAC plus P2Y12 inhibitor - preferably clopidogrel) after a short course of triple antithrombotic therapy (TAT; DAT plus aspirin). Although DAT reduces bleeding risk compared to TAT, this is counterbalanced by an increase in ischaemic events. Aspirin provides early ischaemic benefit, but TAT is associated with an increased haemorrhagic burden; therefore, we propose a 30-day dual antiplatelet therapy (DAPT; aspirin plus P2Y12 inhibitor) strategy post-PCI, temporarily omitting OAC. The study aims to compare bleeding and ischaemic risk between a 30-day DAPT strategy following PCI and a guideline-directed therapy in AF patients requiring OAC. WOEST-3 (ClinicalTrials.gov: NCT04436978) is an investigator-initiated, international, open-label, randomised controlled trial (RCT). AF patients requiring OAC who have undergone successful PCI will be randomised within 72 hours after PCI to guideline-directed therapy (edoxaban plus P2Y12 inhibitor plus limited duration of aspirin) or a 30-day DAPT strategy (P2Y12 inhibitor plus aspirin, immediately discontinuing OAC) followed by DAT (edoxaban plus P2Y12 inhibitor). With a sample size of 2,000 patients, this trial is powered to assess both superiority for major or clinically relevant non-major bleeding and non-inferiority for a composite of all-cause death, myocardial infarction, stroke, systemic embolism or stent thrombosis. In summary, the WOEST-3 trial is the first RCT temporarily omitting OAC in AF patients, comparing a 30-day DAPT strategy with guideline-directed therapy post-PCI to reduce bleeding events without hampering efficacy.

Standards for quantitative assessments by coronary computed tomography angiography (CCTA): An expert consensus document of the society of cardiovascular computed tomography (SCCT).

In current clinical practice, qualitative or semi-quantitative measures are primarily used to report coronary artery disease on cardiac CT. With advancements in cardiac CT technology and automated post-processing tools, quantitative measures of coronary disease severity have become more broadly available. Quantitative coronary CT angiography has great potential value for clinical management of patients, but also for research. This document aims to provide definitions and standards for the performance and reporting of quantitative measures of coronary artery disease by cardiac CT.

Ten-Year Outcome of Recanalization or Medical Therapy for Concomitant Chronic Total Occlusion After Myocardial Infarction.

BACKGROUND: The EXPLORE (Evaluating Xience and Left Ventricular Function in PCI on Occlusions After STEMI) trial was the first and only randomized trial investigating chronic total occlusion (CTO) percutaneous coronary intervention (PCI) early after primary PCI for ST-segment-elevation myocardial infarction, compared with medical therapy for the CTO. We performed a 10-year follow-up of EXPLORE to investigate long-term safety and clinical impact of CTO PCI after ST-segment-elevation myocardial infarction, compared with no-CTO PCI. METHODS AND RESULTS: In EXPLORE, 302 patients post-ST-segment-elevation myocardial infarction with concurrent CTO were randomized to CTO PCI within ≈1 week or no-CTO PCI. We performed an extended clinical follow-up for the primary end point of major adverse cardiac events, consisting of cardiovascular death, coronary artery bypass grafting, or myocardial infarction. Secondary end points included all-cause death, angina, and dyspnea. Median follow-up was 10 years (interquartile range, 8-11 years). The primary end point occurred in 25% of patients with CTO PCI and in 24% of patients with no-CTO PCI (hazard ratio [HR], 1.11 [95% CI, 0.70-1.76]). Cardiovascular mortality was higher in the CTO PCI group (HR, 2.09 [95% CI, 1.10-2.50]), but all-cause death was similar (HR, 1.53 [95% CI, 0.93-2.50]). Dyspnea relief was more frequent after CTO PCI (83% versus 65%, P=0.005), with no significant difference in angina. CONCLUSIONS: This 10-year follow-up of patients post-ST-segment-elevation myocardial infarction randomized to CTO PCI or no-CTO PCI demonstrated no clinical benefit of CTO PCI in major adverse cardiac events or overall mortality. However, CTO PCI was associated with a higher cardiovascular mortality compared with no-CTO PCI. Our long-term data support a careful weighing of effective symptom relief against an elevated cardiovascular mortality risk in CTO PCI decisions. REGISTRATION: URL: https://www.trialregister.nl; Unique identifier: NTR1108.

Previous Exercise Levels and Outcome in Patients with New Atrial Fibrillation: "Past Achievements Do Not Predict the Future".

INTRODUCTION: Long-term endurance exercise is suspect to elevate the risk of atrial fibrillation (AF), but little is known about cardiovascular outcome and disease progression in this subgroup of AF patients. We investigated whether previous exercise level determines cardiovascular outcome. METHODS: In this post hoc analysis of the RACE 4 randomized trial, we analyzed all patients with a completed questionnaire on sports participation. Three subgroups were made based on lifetime sports hours up to randomization and previous compliance to the international physical activity guidelines. High lifetime hours of high dynamic activity patients were defined as more than 150 min·wk -1 of high-intensity physical exercise. The primary endpoint was a composite of cardiovascular death and hospital admissions. RESULTS: A total of 879 patients were analyzed, divided in 203 high lifetime hours of high dynamic activity, 192 high lifetime hours of activity, and 484 low lifetime hours of activity patients. Over a mean follow-up of 36 months (±14), the primary endpoint occurred in 61 out of 203 (30%) high lifetime hours of high dynamic activity, 53 out of 192 (27%) high lifetime hours of activity, and 135 out of 484 (28%) low lifetime hours of activity patients ( P = 0.74). During follow-up, 42 high lifetime hours of high dynamic activity (35%), 43 high lifetime hours of activity (32%), and 104 low lifetime hours of activity patients (34%) with paroxysmal AF received electrical or chemical cardioversion or atrial ablation ( P = 0.90). CONCLUSIONS: In patients included in the RACE 4, there seems to be no relation between previous activity levels and cardiovascular outcome and the need for electrical or chemical cardioversion or atrial ablation. Cardiovascular outcome was driven by AF-related arrhythmic events.

Prognosis of patients in end-stage heart failure with atrial fibrillation treated with ablation: Insights from CASTLE-HTx.

BACKGROUND: The CASTLE-HTx trial demonstrated the benefit of atrial fibrillation (AF) ablation compared with medical therapy in decreasing mortality, need for left ventricular assist device implantation, or heart transplantation (HTx) in patients with end-stage heart failure (HF). OBJECTIVE: This analysis aimed to identify risk factors related to adverse outcomes in patients with end-stage HF and to assess the impact of ablation. METHODS: The CASTLE-HTx protocol randomized 194 patients with end-stage HF and AF to ablation vs medical therapy. We identified left ventricular ejection fraction <30%, New York Heart Association class ≥III, and AF burden >50% as predictors for the primary end point. The CASTLE-HTx risk score assigned weights to these risk factors. Patients with a risk score ≥3 were identified as high risk. RESULTS: The patients were assigned to low-risk (89 [45.9%]) and high-risk (105 [54.1%]) groups. After a median follow-up of 18 months, a primary end point event occurred in 6 and 31 patients of the low- and high-risk groups (hazard ratio, 4.98; 95% confidence interval, 2.08-11.9). The incidence rate (IR) difference between ablation and medical therapy was much larger in high-risk patients (8/49 [IR, 11.4] vs 23/56 [IR, 36.1]) compared with low-risk patients (2/48 [IR, 2.6] vs 4/41 [IR, 6.3]). The IR difference for ablation was significantly higher in high-risk patients (24.69) compared with low-risk patients (3.70). CONCLUSION: The absolute benefit of ablation is more pronounced in high-risk patients, but low-risk patients may also benefit. The CASTLE-HTx risk score identifies patients with end-stage HF who will particularly benefit from ablation.

Cost-effectiveness of low-dose colchicine in patients with chronic coronary disease in the netherlands.

AIMS: Recent trials have shown that low-dose colchicine (0.5 mg once daily) reduces major cardiovascular events in patients with acute and chronic coronary syndromes. We aimed to estimate the cost-effectiveness of low-dose colchicine therapy in patients with chronic coronary disease when added to standard background therapy. METHODS AND RESULTS: This Markov cohort cost-effectiveness model used estimates of therapy effectiveness, transition probabilities, costs and quality of life obtained from the Low-dose Colchicine 2 (LoDoCo2) trial, as well as meta-analyses and public sources. In this trial, Low-dose colchicine was added to standard of care and compared to placebo. The main outcomes were cardiovascular events including myocardial infarction, stroke and coronary revascularisation, quality-adjusted life-year (QALY), the cost per QALY gained (incremental cost-effectiveness ratio), and net monetary benefit. In the model, low-dose colchicine therapy yielded 0.04 additional QALYs compared with standard of care at an incremental cost of €455 from a societal perspective and €729 from a healthcare perspective, resulting in a cost per QALY gained of €12,176/QALY from a societal perspective and €19,499/QALY from a healthcare perspective. Net monetary benefit was €1,414 from a societal perspective and €1,140 from a healthcare perspective. Low-dose colchicine has a 96% and 94% chance of being cost effective, from respectively a societal and healthcare perspective when using a willingness to pay of €50,000/QALY. Net monetary benefit would decrease below zero when annual low-dose colchicine costs would exceed an annual cost of €221 per patient. CONCLUSION: Adding low-dose colchicine to standard of care in patients with chronic coronary disease is cost-effective according to commonly accepted thresholds in Europe and Australia and compares favourably in cost-effectiveness to other drugs used in chronic coronary disease.

Standardized classification and framework for reporting, interpreting, and analysing medication non-adherence in cardiovascular clinical trials: a consensus report from the Non-adherence Academic Research Consortium (NARC)

Non-adherence has been well recognized for years to be a common issue that significantly impacts clinical outcomes and health care costs. Medication adherence is remarkably low even in the controlled environment of clinical trials where it has potentially complex major implications. Collection of non-adherence data diverge markedly among cardiovascular randomized trials and, even where collected, is rarely incorporated in the statistical analysis to test the consistency of the primary endpoint(s). The imprecision introduced by the inconsistent assessment of non-adherence in clinical trials might confound the estimate of the calculated efficacy of the study drug. Hence, clinical trials may not accurately answer the scientific question posed by regulators, who seek an accurate estimate of the true efficacy and safety of treatment, or the question posed by payers, who want a reliable estimate of the effectiveness of treatment in the marketplace after approval. The Non-adherence Academic Research Consortium is a collaboration among leading academic research organizations, representatives from the U.S. Food and Drug Administration and physician-scientists from the USA and Europe. One in-person meeting was held in Madrid, Spain, culminating in a document describing consensus recommendations for reporting, collecting, and analysing adherence endpoints across clinical trials. The adoption of these recommendations will afford robustness and consistency in the comparative safety and effectiveness evaluation of investigational drugs from early development to post-marketing approval studies. These principles may be useful for regulatory assessment, as well as for monitoring local and regional outcomes to guide quality improvement initiatives.(AU)

Comparison of balloon-expandable vs. self-expandable valves in patients undergoing transfemoral transcatheter aortic valve implantation: from the CENTER-collaboration

AIMS: The aim of this study was to compare clinical outcomes of patients undergoing transfemoral transcatheter aortic valve implantation (TAVI) with balloon-expandable (BE) valves vs. self-expandable (SE) valves. Transcatheter aortic valve implantation is a minimally invasive and lifesaving treatment in patients with aortic valve stenosis. Even though BE-valves and SE-valves are both commonly used on a large scale, adequately sized trials comparing clinical outcomes in patients with severe aortic valve stenosis treated with BE-valves compared with SE-valves are lacking. METHODS AND RESULTS: In this CENTER-collaboration, data from 10 registries or clinical trials, selected through a systematic search, were pooled and analyzed. Propensity score methodology was used to reduce treatment selection bias and potential confounding. The primary endpoints were mortality and stroke at 30 days follow-up in patients treated with BE-valves compared with SE-valves. Secondary endpoints included clinical outcomes, e.g. bleeding during hospital admission. All outcomes were split for early-generation BE-valves compared with early-generation SE-valves and new-generation BE-valves with new-generation SE-valves. The overall patient population (N = 12 381) included 6239 patients undergoing TAVI with BE-valves and 6142 patients with SE-valves. The propensity matched population had a mean age of 81 ± 7 years and a median STS-PROM score or 6.5% [interquartile range (IQR) 4.0-13.0%]. At 30-day follow-up, the mortality rate was not statistically different in patients undergoing TAVI with BE-valves compared with SE-valves [BE: 5.3% vs. SE: 6.2%, relative risk (RR) 0.9; 95% confidence interval (CI) 0.7-1.0, P = 0.10]. Stroke occurred less frequently in patients treated with BE-valves (BE: 1.9% vs. SE: 2.6%, RR 0.7; 95% CI 0.5-1.0, P = 0.03). Also, patients treated with BE-valves had a three-fold lower risk of requiring pacemaker implantation (BE: 7.8% vs. SE: 20.3%, RR 0.4; 95% CI 0.3-0.4, P < 0.001). In contrast, patients treated with new-generation BE-valves more frequently experienced major and life-threatening bleedings compared with new-generation SE-valves (BE: 4.8% vs. SE: 2.1%, RR 2.3; 95% CI 1.6-3.3, P < 0.001). CONCLUSION: In this study, which is the largest study to compare valve types in TAVI, we demonstrated that the incidence of stroke and pacemaker implantation was lower in patients undergoing transfemoral TAVI with BE-valves compared with SE-valves. In contrast, patients treated with new-generation BE-valves more often suffered from major or life-threatening bleedings than patients with new-generation SE-valves. Mortality at 30-days was not statistically different in patients treated with BE-valves compared with SE-valves. This study was a propensity-matched analysis generated from observational data, accordingly current outcomes will have to be confirmed in a large scale randomized controlled trial. (AU)