Preoperative computed tomography-imaging with patient-specific computer simulation in transcatheter aortic valve implantation: Design and rationale of the GUIDE-TAVI trial.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an established treatment option for patients with severe aortic valve stenosis, but is still associated with relatively high rates of pacemaker implantation and paravalvular regurgitation. Routine preoperative computed tomography (CT) combined with patient-specific computer modelling can predict the interaction between the TAVI device and the patient's unique anatomy, allowing physicians to assess the risk for paravalvular regurgitation and conduction disorders in advance to the procedure. The aim of this trial is to assess potential improvement in the procedural outcome of TAVI by applying CT-based patient-specific computer simulations in patients with suitable anatomy for TAVI. METHODS: The GUIDE-TAVI trial is an international multicenter randomized controlled trial including patients accepted for TAVI by the Heart Team. Patients enrolled in the study will be randomized into 2 arms of each 227 patients. In patients randomized to the use of FEops HEARTGuide (FHG), patient-specific computer simulation with FHG is performed in addition to routine preoperative CT imaging and results of the FHG are available to the operator(s) prior to the scheduled intervention. In patients randomized to no use of FHG, only routine preoperative CT imaging is performed. The primary objective is to evaluate whether the use of FHG will reduce the incidence of mild to severe PVR, according to the Valve Academic Research Consortium 3. Secondary endpoints include the incidence of new conduction disorders requiring permanent pacemaker implantation, the difference between preoperative and final selected valve size, the difference between target and final implantation depth, change of preoperative decision, failure to implant valve, early safety composite endpoint and quality of life. CONCLUSIONS: The GUIDE-TAVI trial is the first multicenter randomized controlled trial to evaluate the value of 3-dimensional computer simulations in addition to standard preprocedural planning in TAVI procedures.

Upper extremity versus lower extremity for secondary access during transcatheter aortic valve implantation: rationale and design of the randomised TAVI XS trial.

BACKGROUND: During transcatheter aortic valve implantation (TAVI), secondary access is required for angiographic guidance and temporary pacing. The most commonly used secondary access sites are the femoral artery (angiographic guidance) and the femoral vein (temporary pacing). An upper extremity approach using the radial artery and an upper arm vein instead of the lower extremity approach using the femoral artery and femoral vein may reduce clinically relevant secondary access site-related bleeding complications, but robust evidence is lacking. TRIAL DESIGN: The TAVI XS trial is a multicentre, randomised, open-label clinical trial with blinded evaluation of endpoints. A total of 238 patients undergoing transfemoral TAVI will be included. The primary endpoint is the incidence of clinically relevant bleeding (i.e. Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding) of the randomised secondary access site (either diagnostic or pacemaker access, or both) within 30 days after TAVI. Secondary endpoints include time to mobilisation after TAVI, duration of hospitalisation, any BARC type 2, 3 or 5 bleeding, and early safety at 30 days according to Valve Academic Research Consortium­3 criteria. CONCLUSION: The TAVI XS trial is the first randomised trial comparing an upper extremity approach to a lower extremity approach with regard to clinically relevant secondary access site-related bleeding complications. The results of this trial will provide important insights into the safety and efficacy of an upper extremity approach in patients undergoing transfemoral TAVI.

Generalisability of trials on antithrombotic treatment intensification in patients with cardiovascular disease.

OBJECTIVE: Assessment of generalisability of guideline-informing trials on antithrombotic treatment intensification to real-world patients with cardiovascular disease (CVD). METHODS: Inclusion and exclusion criteria of the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS), Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA), Prevention of Cardiovascular events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction (PEGASUS-TIMI) and Dual Antiplatelet Therapy (DAPT) study were applied to coronary artery disease (CAD) and/or peripheral artery disease (PAD) patients from Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease (UCC-SMART) to determine real-world eligibility. Eligible and ineligible patients were compared on baseline characteristics, cardiovascular events, major bleeding and mortality. RESULTS: Eligibility ranged from 11%-94% for CAD to 75%-90% for patients with PAD. Cardiovascular, bleeding and mortality risks were higher in COMPASS-eligible patients with CAD (rate ratios (RR) 1.98 (95% CI 1.74 to 2.26), 2.02 (95% CI 1.47 to 2.78) and 3.11 (95% CI 2.71 to 3.57), respectively) and CHARISMA-eligible patients (RR 1.51 (95% CI 1.12 to 2.06), 2.25 (95% CI 1.01 to 6.21) and 4.43 (95% CI 2.79 to 7.51), respectively), and lower in COMPASS-eligible patients with PAD (RR 0.45 (95% CI 0.36 to 0.56), 0.29 (95% CI 0.18 to 0.46) and 0.45 (95% CI 0.38 to 0.54), respectively) and DAPT-eligible patients with CAD (RR CVD 0.49 (95% CI 0.34 to 0.69) and mortality 0.67 (95% CI 0.48 to 0.94)) than ineligible patients. After adjustment for trial eligibility criteria, only higher cardiovascular and mortality risks in COMPASS-eligible patients with CAD and lower cardiovascular risks in CHARISMA-eligible and DAPT-eligible patients persisted with CAD. CONCLUSION: A large proportion of contemporary CVD patients would be eligible for intensified antithrombotic treatment trials, with mostly similar adjusted event risks to ineligible patients. Trial-based guideline recommendations are largely applicable to real-world patients.

Prehospital Tirofiban Increases the Rate of Disrupted Myocardial Infarction in Patients with ST-Segment Elevation Myocardial Infarction: Insights From the On-TIME 2 Trial.

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI), prehospital tirofiban significantly improved myocardial reperfusion. However, its impact on the rate of disrupted myocardial infarction (MI), particularly in the context of high-sensitive cardiac troponin (hs-cTn) assays, is still unclear. METHODS: The On-TIME 2 (The Ongoing Tirofiban In Myocardial infarction Evaluation 2) trial randomly assigned STEMI patients to prehospital tirofiban or placebo before transportation to a percutaneous coronary intervention (PCI) centre. In this post hoc analysis, we evaluated STEMI patients that underwent primary PCI and had measured hs-cTn levels. Troponin T levels were collected at 18-24 h and 72-96 h after PCI. Disrupted MI was defined as peak hs-cTn T levels ≤10 times the upper limit of normal (≤140 ng/L). RESULTS: Out of 786 STEMI patients, 47 (6%) had a disrupted MI. Disrupted MI occurred in 31 of 386 patients (8.0%) in the tirofiban arm and in 16 of 400 patients (4.0%) in the placebo arm (p=0.026). After multivariate adjustment, prehospital tirofiban remained independently associated with disrupted MI (OR 2.03; 95% CI 1.10 to 3.87; P= 0.027). None of the patients with disrupted MI died during the one-year follow-up, compared to a mortality rate of 2.6% among those without disrupted MI. CONCLUSION: Among STEMI patients undergoing primary PCI, the use of prehospital tirofiban was independently associated with a higher rate of disrupted MI. These results, highlighting a potential benefit, underscore the need for future research focusing on innovative pretreatment approaches which may increase the rate of disrupted MI.

Antithrombotic therapy for transcatheter structural heart intervention.

Percutaneous transcatheter structural heart interventions have considerably expanded within the last two decades, improving clinical outcomes and quality of life versus guideline-directed medical therapy for patients frequently ineligible for surgical treatment. Transcatheter structural heart interventions comprise valve implantation or repair and also occlusions of the patent foramen ovale, atrial septal defects and left atrial appendage. These procedures expose structural devices to arterial or venous blood flow with various rheological conditions leading to potential thrombotic complications and embolisation. Furthermore, these procedures may concern comorbid patients at high risk of both ischaemic and bleeding complications. This state-of-the-art review provides a description of the device-related thrombotic risk associated with these transcatheter structural heart interventions and of the current evidence-based guidelines regarding antithrombotic treatments. Gaps in evidence for each of the studied transcatheter interventions and the main ongoing trials are also summarised.

Outcomes of newly diagnosed atrial fibrillation in patients with acute coronary syndromes.

BACKGROUND: Acute coronary syndrome (ACS) is frequently accompanied by newly diagnosed atrial fibrillation (AF). AIMS: We aimed to compare the risk of major adverse cardiovascular events (MACE) in ACS patients presenting with known, newly diagnosed, or no AF. METHODS: In our multicentre, prospective registry study, we included patients with confirmed ACS. Patients are classified as having known, newly diagnosed or no AF. Newly diagnosed AF is subdivided according to the duration of the episode, time of onset, post-coronary artery bypass graft (CABG) or spontaneous occurrence, and treatment with oral anticoagulants (OAC). The primary endpoint is MACE at 1 year. Key secondary endpoints include ischaemic stroke and bleeding complications. RESULTS: Amongst 4,433 patients with confirmed ACS, 3,598 (81.2%) had no AF, 438 (9.9%) had newly diagnosed AF, and 397 (9.0%) had known AF. The rates of OAC treatment at discharge were 53.4% in patients with newly diagnosed AF and 89.2% in patients with known AF. After adjusting for baseline imbalances, only new AF was independently associated with increased rates of MACE, whereas known AF was not (hazard ratio [HR] 1.52, 95% confidence interval [CI]: 1.19-1.90 and HR 0.93, 95% CI: 0.70-1.23). For ACS patients with newly diagnosed AF, episodes lasting >24 hours were associated with a higher risk of MACE compared to episodes <24 hours (HR 1.99, 95% CI: 1.36-2.93). Episodes of new AF occurring post-CABG had more favourable outcomes compared to spontaneously occurring new AF (HR for MACE 0.52, 95% CI: 0.31-0.86). OAC treatment rates were higher in the new AF subcategories with higher rates of MACE and ischaemic stroke. CONCLUSIONS: Newly diagnosed AF in ACS patients was associated with higher rates of MACE and ischaemic stroke compared to ACS patients without or with known AF. Among the ACS patients with new AF, an episode lasting >24 hours was associated with worse outcomes than shorter episodes, while post-CABG occurrence of AF showed relatively better outcomes compared to spontaneously occurring AF. Only 53% of new AF patients were discharged on OAC therapy versus 89% with known AF.

Pre-hospital evaluation of chest pain patients using the modified HEART-score: rationale and design.

Background: This study assesses how ambulance paramedics using the modified HEART-score with a point-of-care cardiac troponin (cTn) compare to the emergency physicians using the modified HEART-score with a high-sensitive cTn (hs-cTn) in patients with suspected non-ST-elevation acute coronary syndrome (NSTE-ACS), focusing on interobserver agreement and diagnostic performance. Methods: In this prospective multicenter cohort, we compare four cTn testing strategies (serial point of care and hs-cTn cTn measurement) with and without the HEART-score. Outcomes include the HEART-score's interobserver agreement, NSTE-ACS at discharge, major adverse cardiovascular events (MACE) after 30 days, and diagnostic accuracy of the different strategies. Conclusion: The POPular HEART study aims to improve NSTE-ACS diagnostic pathways, promoting pre-hospital detection and ruling out of NSTE-ACS to minimize unnecessary hospitalizations and associated costs.Clinical Trial Registration: NCT04851418 (ClinicalTrials.gov).

What & why? Many people visit the emergency department (ED) due to chest pain, often worried about the possibility of a heart attack. While acute heart attacks can often be detected through an electrocardiogram (ECG; a test of the heart's electrical activity), a significant number of patients with a heart attack have a normal ECG. These patients require further testing to measure cardiac troponin (cTn; an indicator of heart damage) in the hospital to rule out a heart attack, known as non-ST-elevation acute coronary syndrome (NSTE-ACS). To improve diagnosis and care for these patients, we compared two approaches: ambulance paramedics using a quick bedside cTn test and the HEART-score, versus hospital doctors using a more sensitive cTn test with the HEART-score. The HEART score combines factors like the patient's medical history, ECG results, age, risk factors, and cTn levels to assess the risk of heart problems. In this comparison, the key difference lies in how cTn levels are measured ­ either through a quick finger prick test in an ambulance using a point-of-care device or a more detailed analysis in a hospital laboratory.How? We focused on patients visited by emergency medical services for chest pain suspected of a heart attack and transported to the hospital. We assessed the quick bedside test by paramedics and the detailed hospital test by doctors, alongside the use of the HEART score in both settings. Our evaluation looked at the agreement between these methods and their effectiveness in identifying or excluding an NSTE-ACS.What? Our research, known as the POPular HEART study, seeks to simplify the early identification or rule-out of an NSTE-ACS in patients with chest pain directly by ambulance. This approach aims to decrease unnecessary hospital admissions and reduce healthcare costs.Main points We're exploring innovative methods to safely identify patients with a very low risk of NSTE-ACS in individuals with chest pain outside the hospital. Our objective is to safely minimize hospital admissions that may not be necessary, thereby saving resources. By doing so, we aim to alleviate the pressure on EDs and contribute to more cost-effective healthcare.

Adding Surgical Edge-to-Edge Mitral Valve Repair to Myectomy in Hypertrophic Obstructive Cardiomyopathy: Long-Term Functional and Echocardiographic Outcome.

This study evaluates the early and long-term clinical and echocardiographic outcome of edge-to-edge (E2E) mitral valve repair (MVr) concomitant to septal myectomy (SM) in patients with symptomatic hypertrophic obstructive cardiomyopathy (HOCM). A retrospective single-center analysis was performed of patients who underwent isolated SM or SM with E2E MVr from 2011 to 2022. Exclusion criteria were primary mitral valve (MV) disease or concomitant valve surgery. Early and long-term safety, functional and echocardiographic outcomes were compared between groups. Between January 2011 and April 2022, 76 consecutive patients underwent SM for HOCM: 42 patients (55%) underwent SM without additional E2E MVr (Group 1) and 34 patients (45%) underwent SM with additional E2E MVr (Group 2). At latest follow-up, 87% of patients were in New York Heart Association (NYHA) class I-II with no significant differences in NYHA class between groups. Incidence of safety events was comparable between groups. Echocardiographic relief of left ventricular outflow tract (LVOT) obstruction was comparable at early follow-up (P = 0.68), with a significant but small difference in maximum LVOT pressure gradient at latest follow-up in favor of E2E MVr (P = 0.04). Furthermore, patients who underwent SM with E2E MVr showed less residual systolic anterior motion at early and latest follow-up (P = 0.020; P = 0.178). Reintervention on the MV was absent in both groups at 1 year and equally low at follow-up (P = 0.27). This study demonstrates that adding E2E MVr to septal myectomy is as safe as isolated myectomy for the treatment of HOCM. Moreover, the addition of E2E MVr is associated with similar excellent functional improvement and freedom from MV reintervention.

Coronary Artery Bypass Graft Failure in Women: Incidence and Clinical Implications.

BACKGROUND: Women have worse outcomes after coronary artery bypass surgery (CABG) than men. OBJECTIVES: This study aimed to determine the incidence of CABG graft failure in women, its association with cardiac events, and whether it contributes to sex-related differences in outcomes. METHODS: A pooled analysis of individual patient data from randomized clinical trials with systematic imaging follow-up was performed. Multivariable logistic regression models were used to assess the association of graft failure with myocardial infarction and repeat revascularization between CABG and imaging (primary outcome) and death after imaging (secondary outcome). Mediation analysis was performed to evaluate the effect of graft failure on the association between female sex and risk of death. RESULTS: Seven randomized clinical trials (N = 4,413, 777 women) were included. At a median imaging follow-up of 1.03 years, graft failure was significantly more frequent among women than men (37.3% vs 32.9% at the patient-level and 20.5% vs 15.8% at the graft level; P = 0.02 and P < 0.001, respectively). In women, graft failure was associated with an increased risk of myocardial infarction and repeat revascularization (OR: 3.94; 95% CI: 1.79-8.67) and death (OR: 3.18; 95% CI: 1.73-5.85). Female sex was independently associated with the risk of death (direct effect, HR: 1.84; 95% CI: 1.35-2.50) but the association was not mediated by graft failure (indirect effect, HR: 1.04; 95% CI: 0.86-1.26). CONCLUSIONS: Graft failure is more frequent in women and is associated with adverse cardiac events. The excess mortality risk associated with female sex among CABG patients is not mediated by graft failure.

P2Y12 Inhibition in Patients Requiring Oral Anticoagulation After Percutaneous Coronary Intervention: The SWAP-AC-2 Study.

BACKGROUND: Among patients treated with a novel oral anticoagulant (NOAC) undergoing percutaneous coronary intervention (PCI), combination therapy with clopidogrel (ie, known as dual antithrombotic therapy [DAT]) is the treatment of choice. However, there are concerns for individuals with impaired response to clopidogrel. OBJECTIVES: The authors sought to assess the pharmacodynamic (PD) effects of clopidogrel vs low-dose ticagrelor in patients with impaired clopidogrel response assessed by the ABCD-GENE score. METHODS: This was a prospective, randomized PD study of NOAC-treated patients undergoing PCI. Patients with an ABCD-GENE score ≥10 (n = 39), defined as having impaired clopidogrel response, were randomized to low-dose ticagrelor (n = 20; 60 mg twice a day) or clopidogrel (n = 19; 75 mg once a day). Patients with an ABCD-GENE score <10 (n = 42) were treated with clopidogrel (75 mg once a day; control cohort). PD assessments at baseline and 30 days post-randomization (trough and peak) were performed to assess P2Y12 signaling (VerifyNow P2Y12 reaction units [PRU], light transmittance aggregometry, and vasodilator-stimulated phosphoprotein); makers of thrombosis not specific to P2Y12 signaling were also assessed. The primary endpoint was PRU (trough levels) at 30 days. RESULTS: At 30 days, PRU levels were reduced with ticagrelor-based DAT compared with clopidogrel-based DAT at trough (23.0 [Q1-Q3: 3.0-46.0] vs 154.5 [Q1-Q3: 77.5-183.0]; P < 0.001) and peak (6.0 [Q1-Q3: 4.0-14.0] vs 129.0 [Q1-Q3: 66.0-171.0]; P < 0.001). Trough PRU levels in the control arm (104.0 [Q1-Q3: 35.0-167.0]) were higher than ticagrelor-based DAT (P = 0.005) and numerically lower than clopidogrel-based DAT (P = 0.234). Results were consistent by light transmittance aggregometry and vasodilator-stimulated phosphoprotein. Markers measuring other pathways leading to thrombus formation were largely unaffected. CONCLUSIONS: In NOAC-treated patients undergoing PCI with an ABCD-GENE score ≥10, ticagrelor-based DAT using a 60-mg, twice-a-day regimen reduced platelet P2Y12 reactivity compared with clopidogrel-based DAT. (Tailoring P2Y12 Inhibiting Therapy in Patients Requiring Oral Anticoagulation After PCI [SWAP-AC-2]; NCT04483583).

Association between overweight and obesity with coronary artery bypass graft failure: an individual patient data analysis of clinical trials.

OBJECTIVES: The association between obesity and graft failure after coronary artery bypass grafting has not been previously investigated. METHODS: We pooled individual patient data from randomized clinical trials with systematic postoperative coronary imaging to evaluate the association between obesity and graft failure at the individual graft and patient levels. Penalized cubic regression splines and mixed-effects multivariable logistic regression models were performed. RESULTS: Six trials comprising 3928 patients and 12 048 grafts were included. The median time to imaging was 1.03 (interquartile range 1.00-1.09) years. By body mass index (BMI) category, 800 (20.4%) patients were normal weight (BMI 18.5-24.9), 1668 (42.5%) were overweight (BMI 25-29.9), 983 (25.0%) were obesity class 1 (BMI 30-34.9), 344 (8.8%) were obesity class 2 (BMI 35-39.9) and 116 (2.9%) were obesity class 3 (BMI 40+). As a continuous variable, BMI was associated with reduced graft failure [adjusted odds ratio (aOR) 0.98 (95% confidence interval (CI) 0.97-0.99)] at the individual graft level. Compared to normal weight patients, graft failure at the individual graft level was reduced in overweight [aOR 0.79 (95% CI 0.64-0.96)], obesity class 1 [aOR 0.81 (95% CI 0.64-1.01)] and obesity class 2 [aOR 0.61 (95% CI 0.45-0.83)] patients, but not different compared to obesity class 3 [aOR 0.94 (95% CI 0.62-1.42)] patients. Findings were similar, but did not reach significance, at the patient level. CONCLUSIONS: In a pooled individual patient data analysis of randomized clinical trials, BMI and obesity appear to be associated with reduced graft failure at 1 year after coronary artery bypass grafting.

Defining high bleeding risk in patients undergoing transcatheter aortic valve implantation: a VARC-HBR consensus document.

The identification and management of patients at high bleeding risk (HBR) undergoing transcatheter aortic valve implantation (TAVI) are of major importance, but the lack of standardised definitions is challenging for trial design, data interpretation, and clinical decision-making. The Valve Academic Research Consortium for High Bleeding Risk (VARC-HBR) is a collaboration among leading research organisations, regulatory authorities, and physician-scientists from Europe, the USA, and Asia, with a major focus on TAVI-related bleeding. VARC-HBR is an initiative of the CERC (Cardiovascular European Research Center), aiming to develop a consensus definition of TAVI patients at HBR, based on a systematic review of the available evidence, to provide consistency for future clinical trials, clinical decision-making, and regulatory review. This document represents the first pragmatic approach to a consistent definition of HBR evaluating the safety and effectiveness of procedures, devices and drug regimens for patients undergoing TAVI..

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.

Rescate transfemoral en un dispositivo TAVI transapical mal posicionado / Transfemoral rescue for a transapical malpositioned TAVI device

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