Reduction of Cardiac Allograft Vasculopathy by PCI: Quantification and Correlation With Outcome After Heart Transplantation.

BACKGROUND: Percutaneous coronary intervention (PCI) might improve outcome at severe stages of cardiac allograft vasculopathy (CAV) among patients after heart transplantation (HTx). Yet, risk stratification of HTx patients after PCI remains challenging. AIMS: To assess whether the International Society for Heart and Lung Transplantation (ISHLT) CAV classification remains prognostic after PCI and whether risk-stratification models of non-transplanted patients extend to HTx patients with CAV. METHODS: At 2 European academic centers, 203 patients were stratified in cohort 1 (ISHLT CAV1, without PCI, n = 126) or cohort 2 (ISHLT CAV2 and 3, with PCI). At first diagnosis of CAV or first PCI, respectively, ISHLT CAV grades, SYNTAX scores I and II (SXS-I, SXS-II) were used to quantify baseline and residual CAV (rISHLT, rSXS-I, rSXS-II). RSXS-I > 0 defined incomplete revascularization (IR). RESULTS: SXS-II predicted mortality in cohort 1 (P = 0.004), whereas SXS-I (P = 0.009) and SXS-II (P = 0.002) predicted mortality in cohort 2. Post-PCI, IR (P = 0.004), high rISHLT (P = 0.02) and highest tertile of rSXS-II (P = 0.006) were associated with higher 5-year mortality. In bivariable Cox analysis, baseline SXS-II, IR and rSXS-II remained predictors of 5-year mortality post-PCI. There was a strong inverse relationship between baseline and rSXS-I (r = -0.55; P < 0.001 and r = -0.50; P = 0.003, respectively) regarding the interval to first reintervention. CONCLUSION: People with ISHLT CAV classification could apply for risk stratification after PCI. SYNTAX scores could be complemental for risk stratification and individualization of invasive follow-up of HTx patients with CAV.

Right Ventriculoarterial Coupling Surrogates and Long-Term Survival in LVAD Recipients: Results of the ASSIST-ICD Multicentric Registry.

BACKGROUND: Prediction of outcomes remains an unmet need in candidates for LVADs. The development of right-heart failure portends an excess in mortality rates, but imaging parameters of right ventricular systolic function have failed to demonstrate a prognostic role. By integrating pulmonary pressure, right ventriculoarterial coupling could fill this gap. METHODS: The ASSIST-ICD registry was used to test right ventriculoarterial coupling as a surrogate parameter at implantation for the prediction of all-cause mortality. RESULTS: The ratio of the tricuspid annular-plane systolic excursion over the estimated systolic pulmonary pressure (TAPSE/sPAP) was not associated with long-term survival in univariate analysis (P = 0.89), nor was the pulmonary artery pulsatility index (PAPi) (P = 0.13). Conversely, the ratio of the right atrial pressure over the pulmonary capillary wedge pressure (RAP/PCWP) was associated with all-cause mortality (P < 0.01). After taking tricuspid regurgitation severity, LVAD indication, LVAD model, age, blood urea nitrogen levels, and pulmonary vascular resistance into account, RAP/PCWP remained associated with survival (HR 1.35 [1.10 - 1.65]; P < 0.01). CONCLUSION: Among pre-implant RVAC surrogates, only RAP/PCWP was associated with long-term all-cause mortality in LVAD recipients. This association was independent of established risk factors.

Impact of peri-procedural management of direct oral anticoagulants on pocket haematoma after cardiac electronic device implantation: the StimAOD multicentre prospective study.

AIMS: The study aims to investigate the impact of direct oral anticoagulant (DOAC) management on the incidence of pocket haematoma in patients undergoing pacemaker or implantable cardioverter-defibrillator implantation. METHODS AND RESULTS: All consecutive patients receiving DOAC and undergoing cardiac electronic device implantation were included in a large multicentre prospective observational study (NCT03879473). The primary endpoint was clinically relevant haematoma within 30 days after implantation. Overall, 789 patients were enrolled [median age 80 (IQR 72-85) years old, 36.4% women, median CHA2DS2-VASc score 4 (IQR 0-8)], of which 632 (80.1%) received a pacemaker implantation. Antiplatelet therapy was combined with DOAC in 146 patients (18.5%). Direct oral anticoagulants (DOACs) were interrupted 52 (IQR 37-62) h before the procedure and resumed 31 (IQR 21-47) h later. Ninety-six percent of the patients had at least 12 h DOAC interruption before the procedure, and 78% had at least 12 h DOAC interruption after the procedure. Overall, anticoagulation was interrupted for 72 (IQR 48-96) h. Pre- or post-procedural heparin bridging was used in 8.2% and 3.9%, respectively. Timing of DOAC interruption of resumption was not associated with clinically relevant haematoma. Clinically relevant haematoma occurred in 26 patients (3.3%), and thromboembolic events occurred in 5 patients (0.6%). CONCLUSION: In this large real-life registry where most patients had DOAC interruption, clinically relevant haematoma was rare. Despite DOAC interruption and high CHA2DS2-VASc score, thromboembolic events occurred seldomly, highlighting that bleeding exceeds thromboembolic risk in this peri-procedural period. Future research is needed to identify risk factors for clinically relevant haematoma and meaningfully guide clinicians in optimizing DOAC management.

Use of ADAM-C and CHA2DS2-VASc scores to predict complex aortic atheroma after brain ischemia: A prospective observational study.

BACKGROUND AND AIMS: Complex aortic atheroma (CAA) is a common cause of acute brain ischemia (BI), including ischemic stroke (IS) and transient ischemic attack (TIA), and is associated with recurrence. The CHA2DS2-VASc score is a useful tool for predicting stroke in patients with atrial fibrillation (AF), and can also predict cardiovascular events in other populations, including non-AF populations. The ADAM-C score is a new risk score for predicting the diagnostic yield of transesophageal echocardiography (TEE) after BI. We aimed to evaluate the ability of CHA2DS2-VASc and ADAM-C scores to predict CAA after BI. METHODS: This prospective, multicenter, observational study included 1479 patients aged over 18 years who were hospitalized for BI. CAA was defined as the presence of one or more of the following criteria: thrombus, ulcerated plaque, or plaque thickening ≥ 4 mm. RESULTS: CAA was diagnosed in 216 patients (14.6%). CHA2DS2-VASc and ADAM-C scores were significantly higher in the CAA group versus the non-CAA group (P < .0001 for both). The CHA2DS2-VASc and ADAM-C scores appear to be good predictors of CAA (AUC 0.699 [0.635, 0.761] and 0.759 [0.702, 0.814], respectively). The sensitivity, specificity, predictive positive value (PPV), and negative predictive value (NPV) of the scores for detecting CAA were 94%, 22%, 17%, and 96%, respectively, for a CHA2DS2-VASc score < 2, and 90%, 46%, 22%, and 96%, respectively, for an ADAM-C score < 3 CONCLUSIONS: CHA2DS2-VASc and ADAM-C scores are able to predict CAA after BI. CHA2DS2-VASc < 2 and ADAM-C < 3 both have an interesting NPV of 96%.

Management of Intraprocedural Anticoagulation in Patients on Non-Vitamin K Antagonist Oral Anticoagulants Undergoing Catheter Ablation for Atrial Fibrillation: Understanding the Gaps in Evidence.

Catheter ablation has gained a prominent role in the management of atrial fibrillation (AF), with recent data providing positive evidence on hard outcomes, including hospitalization and mortality. Ablation, however, exposes the patient to a rather unique situation, combining risks for both major bleeding and thromboembolic events. In this setting, the critical importance of rigorous anticoagulation during the procedure has been underlined, and the latest international guidelines now recommend performing AF catheter ablation with uninterrupted non-vitamin K antagonist oral anticoagulants (NOACs) and concomitant administration of unfractionated heparin adjusted to achieve and maintain a target activated clotting time of ≥300 seconds. Whereas observational studies and randomized controlled trials support the safety and efficacy of uninterrupted NOAC strategy for AF catheter ablation, recent experiences have questioned this point, showing a greater unfractionated heparin requirement in NOAC-treated patients compared with vitamin K antagonists-treated patients to achieve the target activated clotting time. Important gaps in evidence regarding optimal intraprocedural anticoagulation management need to be acknowledged. A thorough appreciation of the physiology of anticoagulation during AF catheter ablation and the relevant differences between vitamin K antagonists and NOACs is required, while also understanding the limitations of activated clotting time measurement with regard to accurate intraprocedural anticogulation monitoring. This review aims to provide a critical look at this relatively ignored aspect of AF catheter ablation, especially pitfalls in NOAC monitoring, and to identify gaps in knowledge that need to be addressed in the near future.

ADAM-C score: New risk score for predicting diagnostic yield of transesophageal echocardiography after cerebral ischemia.

BACKGROUND AND AIM: The clinical utility of transesophageal echocardiography (TEE) after brain ischemia (BI) remains a matter of debate. We aimed to evaluate the clinical impact of TEE and to build a score that could help physicians to identify which patients should better benefit from TEE. METHODS: This prospective, multicenter, observational study included patients over 18 years old, hospitalized for BI. TEE findings were judged discriminant if the results showed important information leading to major changes in the management of patients. Most patients with patent foramen ovale were excluded. Variables independently associated with a discriminant TEE were used to build the prediction model. RESULTS: Of the entire population (1479 patients), 255 patients (17%) were classified in the discriminant TEE group. Five parameters were selected as predictors of a discriminant TEE. Accordingly, the ADAM-C score could be calculated as follows: Score = 4 (if age ≥60) + 2 (if diabetes) + 2 (if aortic stenosis from any degrees) + 1 (if multi-territory stroke) + 2 (if history of coronary artery disease). At a threshold lower than 3, the sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of detecting discriminant TEE were 88% (95% CI 85-90), 44% (95% CI 41-47), 21% (95% CI 19-27), and 95% (95% CI 94-97), respectively. CONCLUSION: A simple score based on clinical and transthoracic echocardiographic parameters can help physicians to identify patients who might not benefit from TEE. Indeed, a score lower than 3 has an interesting NPV of 95% (95% CI 94-97).

Predictors of pre-procedural concentrations of direct oral anticoagulants: a prospective multicentre study.

AIMS: Patients receiving direct oral anticoagulants (DOACs) frequently undergo elective invasive procedures. Their management is challenging. We aimed to determine the optimal duration of DOAC discontinuation that ensures a minimal anticoagulant effect during the procedure. METHODS AND RESULTS: This prospective multicentre study included 422 DOAC-treated patients requiring an invasive procedure. Pre-procedural DOAC concentration ([DOAC]) and routine haemostasis assays were performed to determine i/the proportion of patients who achieved a minimal pre-procedural [DOAC] (≤30 ng/mL) according to the duration of DOAC discontinuation, ii/the predictors of minimal [DOAC] and, iii/the ability of routine assays to predict minimal [DOAC]. Lastly, we assessed the predictors of peri-procedural bleeding events. The duration of DOAC discontinuation ranged from 1 to 218 h and pre-procedural [DOAC] from ≤30 to 527 ng/mL. After a 49-72-h discontinuation, 95% of the [DOAC] were ≤30 ng/mL. A 72-h discontinuation predicted concentrations ≤30 ng/mL with 91% specificity. In multivariable analysis, duration of DOAC discontinuation, creatinine clearance <50 mL/min and antiarrhythmics were independent predictors of minimal pre-procedural [DOAC] (concordance statistic 0.869; 95% confidence interval: 0.829-0.912). Conversely, routine haemostasis assays were poor predictors. Last, creatinine clearance <50 mL/min, antiplatelets and high-bleeding risk procedures were predictors of bleeding events. CONCLUSION: A last DOAC intake 3 days before a procedure resulted in minimal pre-procedural anticoagulant effect for almost all patients. Moderate renal impairment, especially in dabigatran-treated patients, and antiarrhythmics in anti-Xa-treated patients should result in a longer DOAC interruption. In situations requiring testing, routine assays should not replace DOAC concentration measurement.

The effectiveness of platelet supplementation for the reversal of ticagrelor-induced inhibition of platelet aggregation: An in-vitro study.

BACKGROUND: Management of ticagrelor-induced bleeding is challenging, as no antidote is currently available. Platelet transfusion, usually proposed to reverse antiplatelet drugs, has been suggested to be ineffective but few data are available. OBJECTIVE: To assess the efficacy of platelet supplementation to restore platelet aggregation inhibited by ticagrelor. DESIGN: In vitro study. SETTING: Blood samples were obtained from the French Blood Bank Institute. PARTICIPANTS: Healthy blood donors. INTERVENTIONS: Whole blood from healthy donors was spiked with ticagrelor or aspirin (used as a positive control). MAIN OUTCOME MEASURES: Platelet aggregation was investigated with impedance aggregometry on whole blood [expressed in ohms (V)] and light transmission aggregometry (expressed in %) on platelet-rich plasma using ADP or arachidonic acid as agonists for ticagrelor or aspirin, respectively. Platelet supplementation was defined as the addition of washed platelet suspension increasing at least 60% of whole blood platelet count. RESULTS: Ticagrelor (3.25 mM) inhibited ADP-induced platelet aggregation compared with control either in whole blood (2 vs. 13 V, P < 0.05) or in platelet-rich plasma (15 vs. 75% P < 0.05). Aspirin (25 mM) inhibited arachidonic acid-induced aggregation (1 vs. 7.5 V, P < 0.05 in whole blood and 5 vs. 77.5%, P = 0.01 in platelet-rich plasma). Platelet supplementation completely restored arachidonic acid-induced platelet aggregation in whole blood (10 vs. 1 V, P = 0.008) and platelet-rich plasma (73 vs. 5%, P < 0.01) in aspirin-treated samples, whereas it failed to correct ADP-induced aggregation (2 vs. 2 V in whole blood and 13.5 vs. 15% in platelet-rich plasma, P > 0.05) in ticagrelor-treated samples. We also report a case of a ticagrelor-treated patient in whom platelet transfusion failed to restore ADP-induced platelet aggregation. CONCLUSION: Platelet supplementation restored platelet aggregation in aspirin-spiked but not in ticagrelor-spiked samples. These results do not support the use of platelet transfusion to reverse the effects of ticagrelor.

[New anticoagulants in 2024: Development of factor XI and XIa inhibitors]. / Les nouveaux anticoagulants en 2024 : développement des inhibiteurs du facteur XI et du XIa.

Thrombosis remains one of the leading causes of death in the world. The history of anticoagulation has evolved considerably from non-specific drugs (i.e., heparins and vitamin K antagonists, VKA) to agents that directly target specific coagulation factors (i.e., argatroban, fondaparinux and direct oral anticoagulants, DOAC). Since the last decade, DOAC are widely used in clinical practice because of their ease to use, their favorable pharmacological profile and the fact that they do not require monitoring. However, despite having a better safety profile than vitamin K antagonist, their bleeding risk is not negligible. New anticoagulants targeting the contact phase of coagulation are currently being developed and could make it possible to prevent the risk of thrombosis without impairing hemostasis. Epidemiological and preclinical data on FXI deficiency make FXI a promising therapeutic target. The aim of this review is to summarize the results of the various clinical trials available that focus on FXI/FXIa inhibition, and to highlight the challenges that this new therapeutic class of anticoagulants will face.

[Evaluation of a semi-automated test for quantification of von Willebrand multimers]. / Évaluation d'un test semi-automatisé de quantification des multimères du facteur von Willebrand.

The assessment of von Willebrand factor (VWF) multimer distribution, particularly following the implantation of circulatory support devices, is a crucial parameter in hemostasis. Our study aimed to evaluate the semi-automated quantification of VWF multimers using the Sebia Hydrasys analyzer. Our analysis focused on quantifying high molecular weight, intermediate weight, and low molecular weight VWF multimers. Electrophoretic migration was performed using the Hydrasys 2 scan, and interpretation was carried out using densitometric analysis with the Phoresis software. The Hydrasys scan 2 successfully separated all the expected VWF multimer profiles based on the type of von Willebrand disease. The analysis revealed that in patients with circulatory support devices, elevated levels of plasma VWF rendered multimer migration unanalyzable using the methodology recommended by the manufacturer. Therefore, adjustment to a 100 % VWF antigenic level improved gel precision. We also suggest using as a standardized control the Cryocheck™ plasma, and have established reference values. Overall, this semi-automated, standardized, and optimized VWF multimer analysis system allows for an effective assessment of the VWF multimeric profile.

Undertaking multi-centre randomised controlled trials in primary care: learnings and recommendations from the PULsE-AI trial researchers.

BACKGROUND: Conducting effective and translational research can be challenging and few trials undertake formal reflection exercises and disseminate learnings from them. Following completion of our multicentre randomised controlled trial, which was impacted by the COVID-19 pandemic, we sought to reflect on our experiences and share our thoughts on challenges, lessons learned, and recommendations for researchers undertaking or considering research in primary care. METHODS: Researchers involved in the Prediction of Undiagnosed atriaL fibrillation using a machinE learning AlgorIthm (PULsE-AI) trial, conducted in England from June 2019 to February 2021 were invited to participate in a qualitative reflection exercise. Members of the Trial Steering Committee (TSC) were invited to attend a semi-structured focus group session, Principal Investigators and their research teams at practices involved in the trial were invited to participate in a semi-structured interview. Following transcription, reflexive thematic analysis was undertaken based on pre-specified themes of recruitment, challenges, lessons learned, and recommendations that formed the structure of the focus group/interview sessions, whilst also allowing the exploration of new themes that emerged from the data. RESULTS: Eight of 14 members of the TSC, and one of six practices involved in the trial participated in the reflection exercise. Recruitment was highlighted as a major challenge encountered by trial researchers, even prior to disruption due to the COVID-19 pandemic. Researchers also commented on themes such as the need to consider incentivisation, and challenges associated with using technology in trials, especially in older age groups. CONCLUSIONS: Undertaking a formal reflection exercise following the completion of the PULsE-AI trial enabled us to review experiences encountered whilst undertaking a prospective randomised trial in primary care. In sharing our learnings, we hope to support other clinicians undertaking research in primary care to ensure that future trials are of optimal value for furthering knowledge, streamlining pathways, and benefitting patients.

Sex disparities in cardiogenic shock: Insights from the FRENSHOCK registry.

BACKGROUND: Cardiogenic shock (CS) is the most severe form of acute heart failure. Discrepancies have been reported between sexes regarding delays, pathways and invasive strategies in CS complicating acute myocardial infarction. However, effect of sex on the prognosis of unselected CS remains controversial. OBJECTIVES: The aim was to analyze the impact of sex on aetiology, management and prognosis of CS. METHODS: The FRENSHOCK registry included all CS admitted in 49 French Intensive Care Units (ICU) and Intensive Cardiac Care Units (ICCU) between April and October 2016. RESULTS: Among the 772 CS patients included, 220 were women (28.5%). Women were older, less smokers, with less history of ischemic cardiac disease (20.5% vs 33.6%) than men. At admission, women presented less cardiac arrest (5.5 vs 12.2%), less mottling (32.5 vs 41.4%) and higher LVEF (30 ± 14 vs 25 ± 13%). Women were more often managed via emergency department while men were directly admitted at ICU/ICCU. Ischemia was the most frequent trigger irrespective of sex (36.4% in women vs 38.2%) but women had less coronary angiogram and PCI (45.9% vs 54% and 24.1 vs 31.3%, respectively). We found no major difference in medication and organ support. Thirty-day mortality (26.4 vs 26.5%), transplant or permanent assist device were similar in both sexes. CONCLUSION: Despite some more favorable parameters in initial presentation and no significant difference in medication and support, women shared similar poor prognosis than men. Further analysis is required to cover the lasting gap in knowledge regarding sex specificities to distinguish between differences and inequalities. NCT02703038.

Prevention of perioperative venous thromboembolism: 2024 guidelines from the French Working Group on Perioperative Haemostasis (GIHP) developed in collaboration with the French Society of Anaesthesia and Intensive Care Medicine (SFAR), the French Society of Thrombosis and Haemostasis (SFTH) and the French Society of Vascular Medicine (SFMV) and endorsed by the French Society of Digestive Surgery (SFCD), the French Society of Pharmacology and Therapeutics (SFPT) and INNOVTE (Investigation Network On Venous ThromboEmbolism) network.

BACKGROUND: Any surgical procedure carries a risk for venous thromboembolism (VTE), albeit variable. Improvements in medical and surgical practices and the shortening of care pathways due to the development of day surgery and enhanced recovery after surgery, have reduced the perioperative risk for VTE. OBJECTIVE: A collaborative working group of experts in perioperative haemostasis updated in 2024 the recommendations for the Prevention of perioperative venous thromboembolism published in 2011. METHODS: The addressed questions were defined by 40 experts (GIHP, SFAR, SFTH and SFMV) and formulated in a PICO format. They performed the literature review and formulated recommendations according to the Grading of GRADE system. Recommendations were then validated by a vote determining the strength of each recommendation. Of note, these recommendations do not cover all surgical specialties. Especially, thromboprophylaxis in cardiac surgery, neurosurgery and obstetrics is not addressed. RESULTS: 78 recommendations were formalized into 17 sections, including patient-related VTE risk factors, types of surgery, extreme body weight, renal impairment, mechanical prophylaxis, distal deep vein thrombosis; 27 were found to have a high level of evidence (GRADE 1) and 41 a low level of evidence (GRADE 2) and 10 were expert opinion. All had strong agreement among the experts. CONCLUSIONS: These guidelines help to weigh the perioperative risk for VTE (which includes the risk associated to surgery and the patient-related risk) against the adverse effects of thromboprophylaxis, either pharmacological or mechanical. This includes particularly the bleeding risk induced by antithrombotic drugs as well as costs.

Management of Gastrointestinal Bleeding and Resumption of Oral Anticoagulant Therapy in Patients with Atrial Fibrillation: A Multidisciplinary Discussion.

Direct oral anticoagulants (DOACs) are recommended for the prevention of thromboembolism in patients with atrial fibrillation (AF), and are now preferred over vitamin K antagonists due to their beneficial efficacy and safety profile. However, all oral anticoagulants carry a risk of gastrointestinal (GI) bleeding. Although the risk is well documented and acute bleeding well codified, there is limited high-quality evidence and no guidelines to guide physicians on the optimal management of anticoagulation after a GI bleeding event. The aim of this review is to provide a multidisciplinary critical discussion of the optimal management of GI bleeding in patients with AF receiving oral anticoagulants to help physicians provide individualized treatment for each patient and optimize outcomes. It is important to perform endoscopy when a patient presents with bleeding manifestations or hemodynamic instability to determine the bleed location and severity of bleeding and then perform initial resuscitation. Administration of all anticoagulants and antiplatelets should be stopped and bleeding allowed to resolve with time; however, anticoagulant reversal should be considered for patients who have life-threatening bleeding or when the bleeding is not controlled by the initial resuscitation. Anticoagulation needs to be timely resumed considering that bleeding risk outweighs thrombotic risk when anticoagulation is resumed early after the bleeding event. To prevent further bleeding, physicians should prescribe anticoagulant therapy with the lowest risk of GI bleeding, avoid medications with GI toxicity, and consider the effect of concomitant medications on potentiating the bleeding risk.

Development of new anticoagulant in 2023: Prime time for anti-factor XI and XIa inhibitors.

Thrombosis remains one of the leading causes of death in the world. The history of anticoagulation has evolved considerably from non-specific drugs (i.e., heparins and vitamin K antagonists, VKA) to agents that directly target specific coagulation factors (i.e., argatroban, fondaparinux and direct oral anticoagulants, DOAC). Since the last decade, DOAC are widely used in clinical practice because of their ease to use with favorable pharmacological profile and not requiring monitoring, particularly for venous thromboembolism treatment and prevention and stroke prevention in atrial fibrillation. However, despite having a better safety profile than VKA, their bleeding risk is not negligible. Therefore, research is underway to develop new anticoagulant therapies with a better safety profile. One of these news approaches to reduce the risk of bleeding is to target the coagulation in the intrinsic pathway, in particular the contact activation, with the ultimate goal of preventing thrombosis without impairing hemostasis. Based on epidemiological data with patients with inherited factor XI (FXI) deficiency and preclinical studies, FXI emerged as the most promising candidate target separating hemostasis from thrombosis. This review summaries the role of FXI and FXIa in hemostasis, provides evidence of initial success with FXI pathway inhibitors in clinical trials (such as IONIS-FXIRx, fesomersen, osocimab, abelacimab, milvexian, asundexian or xisomab 3G3) and highlights the opportunities and challenges for this next generation of anticoagulants.