Isabelle C. Van Gelder

Aims: Early rhythm-control improves cardiovascular outcomes in patients with atrial fibrillation (AF). Its effectiveness in patients with cancer is unclear. This study evaluated the effects of cancer history on early rhythm control in the EAST-AFNET 4 trial. Methods and results: This secondary analysis of EAST-AFNET 4 compared patients with and without a history of cancer, including active cancer and cancer in remission. Outcomes included the primary outcome, a composite of cardiovascular death, stroke, or hospitalization for worsening heart failure or acute coronary syndrome; the safety outcome, a composite of death, stroke, and serious adverse events related to rhythm control; and rhythm at 24 months. Cancer history was available in 2779 of 2789 patients (99.6%). Cancer history was present in 216 of 2779 (7.8%; 19 with active cancer; mean age, 73 years; 95 [44%] women; mean CHA2DS2-VASc score, 3.5). During a follow-up of 8.6 years, early rhythm control reduced the primary outcome in patients with and without a history of cancer (Pinteraction = 0.23) with high rates of sinus rhythm at 24 months (cancer: 84.9%, without cancer: 81.8%; Pinteraction = 0.60). In patients with a cancer history, there was a signal for more safety outcomes with early rhythm control [early rhythm control 36/116 (31%) patients with event, 22 deaths; usual care 20/100 (20%) patients with event, 18 deaths; Pinteraction = 0.055]. Conclusion: Early rhythm control therapy appears effective in patients with AF and a history of cancer but may be less safe than in patients without cancer, in this hypothesis-generating analysis. This could be a play of chance but warrants further research into the safety and efficacy of rhythm control therapy in patients with a cancer history. Trial Registration: ClinicalTrials.gov Identifier: NCT01288352

Background and Aims: Atrial cardiomyopathy (AtCM) is associated with atrial fibrillation (AF). While histological studies describe underlying mechanisms of AtCM, these insights remain disconnected from clinical AtCM. This study determines the histological basis of non-invasive AtCM markers and assess their prognostic value in patients undergoing cardiac surgery. Methods and results: Left and right (LA/RA) atrial tissue samples were obtained in patients undergoing cardiac surgery (n = 136) in the RACE V Tissue Bank study. Pre-operative rhythm history, digital ECG, transthoracic echocardiography (TTE) and biomarker levels were used to group patients in AtCM stages: AF: history of paroxysmal, persistent or permanent AF, Severe (LAVi>50 mL/m2 or LAEF250 pg/mL), Mild (no AF, LAVi≤34 mL/m2 AND P-terminal Force V1 > 5 mV*ms OR P wave duration > 120 ms), and no AtCM. Tissue was stained (WGA/CD31/Vimentin) to quantify fibrosis, fibroblast density, myocyte diameter and vascularization. Post-operative rhythm was monitored continuously (2.5 years) using implantable loop recorders. Patients with severe AtCM had extended endomysial fibrosis (LA: +0.82µm, pFDR,LA < 0.001; RA: +0.64µm, pFDR,RA = 0.010) and larger left atrial cardiomyocytes (LA: +0.92µm, pFDR,LA = 0.026). Moderate AtCM patients showed LA myocyte hypertrophy (LA: +1.35µm, pFDR,LA = 0.007). Mild AtCM patients had similar histological features to patients without AtCM. Moderate (β = 3.56, pFDR = 0.045) and severe (β = 3.74, pFDR = 0.034) AtCM patients had a higher AF burden late after cardiac surgery. Conclusion: Clinical AtCM markers reflect pro-fibrotic and pro-hypertrophic remodelling in the moderate to severe AtCM stages and are associated with a higher AF burden late after surgery.

Atrial cardiomyopathy (ACMP) encompasses structural, electrical and functional atrial abnormalities that have been associated with ischaemic stroke, heart failure and mortality, independent of atrial fibrillation (AF). Increasing evidence suggests that AF, stroke and other adverse outcomes may represent parallel manifestations of ACMP. In the present narrative review, we synthesise current experimental and clinical evidence on the risk factors, pathophysiology, diagnosis and stages of ACMP, and summarise its bidirectional interactions with affected organs, including the left ventricle, lungs, brain, kidneys and gut. ACMP can be considered as an upstream disease process driven by fibrosis, inflammation, oxidative stress, hypercoagulability, metabolic stress and adipose tissue. Through haemodynamic, neurohormonal, inflammatory and thrombotic pathways, ACMP both contributes to and results from dysfunction in other organs, forming self-perpetuating cycles. ACMP can be characterised using complementary electrical, structural, functional and biomarker-based measures, although no single diagnostic standard exists. Disease progression appears staged, with earlier phases potentially reversible and advanced stages dominated by more permanent structural remodelling. Collectively, the evidence supports considering ACMP as a multiorgan disease, highlighting the need for an atrium-centred, integrated approach to risk stratification, preventive and therapeutic strategies.

Background Preventing high heart rates in atrial fibrillation (AF) is recommended to reduce AF-related symptoms and morbidity. Evidence on a strong relationship between lower heart rate during AF and a reduction in symptoms or cardiovascular complications is, however, lacking. Methods This Early Treatment of Atrial Fibrillation for Stroke Prevention Trial analysis compared symptoms, treatment strategy and the composite of death from cardiovascular causes, stroke or hospitalisation with worsening of heart failure or acute coronary syndrome between patients with a heart rate Results At baseline, 772 patients were in AF and had information on heart rate available. Mean age was 70.8±7.8 years, 305 (40%) were women, 385 (50%) were randomised to early rhythm control and 506 (66%) patients had a heart rate Conclusion A high heart rate (≥110 beats per minute) during AF is associated with more and more severe AF-related symptoms. Cardiovascular event rates are not different between heart rates. Early rhythm control reduces outcomes in patients with high and low heart rates during AF. Trial registration number NCT01288352.

The European Society of Cardiology (ESC) develops and updates clinical practice guidelines (CPGs) based on the latest evidence. However, their implementation remains suboptimal, leading to missed opportunities to improve cardiovascular (CV) outcomes. The success of CPG implementation is influenced by four key factors: (i) patient-related barriers, (ii) health care professionals’ engagement, (iii) the clarity and usability of CPGs, and (iv) the health care system and economic context in which care is delivered. To address these challenges, innovative strategies are needed to bridge the gap between CPG recommendations and clinical practice. The ESC has developed several initiatives to improve implementation, including (i) educational programmes, (ii) examinations for cardiologists, (iii) accreditation policies, and (iv) registries. However, persistent gaps indicate that knowledge dissemination alone is insufficient. A more integrated, structured, and equitable approach to quality-of-care improvement is required. Despite the need for evidence-based implementation strategies, only a limited number of high-quality randomized controlled trials have evaluated individual approaches for CV conditions. Strategies such as text messaging, educational interventions, the involvement of non-physician health workers, structured order sheets, and financial incentives have been tested, but their feasibility and effectiveness can vary across health care systems. Future research should explore the potential of artificial intelligence-enhanced technologies to support and scale implementation efforts. This manuscript reviews current evidence on CPG implementation and proposes strategies to enhance the adoption of best practices in CV care.

Aims: Patients with persistent atrial fibrillation (AF) and heart failure (HF) have compromised clinical outcomes. Contemporary management includes rhythm control with AF ablation, or rate control and regularization with conduction system pacing and atrioventricular nodal ablation (CSP + AVNA). These strategies have never been compared in a randomized clinical trial. The study aims to determine whether CSP + AVNA is superior to AF ablation for reducing all-cause mortality and cardiovascular hospitalization, and noninferior with respect to all-cause mortality and heart failure hospitalization. Methods and results: ABACUS is a multicentre, investigator-initiated, randomized controlled trial enrolling 220 patients with persistent AF and HF, aged >60 years, who are eligible for both treatment modalities, with at most one previous AF ablation procedure. Participants will be randomized 1:1 to either catheter ablation of AF (with pulmonary vein isolation using any routine technique) or to CSP + AVNA. All patients will undergo at least one year of follow-up. The co-primary endpoints will be tested sequentially. A number of predefined secondary endpoints, including costs, will also be evaluated. Discussion: ABACUS compares CSP + AVNA with AF ablation in patients with persistent AF and HF. The results will provide evidence to improve care in this vulnerable patient population.