Detection of subclinical atrial fibrillation with cardiac implanted electronic devices: What decision making on anticoagulation after the NOAH and ARTESiA trials?

Atrial fibrillation (AF) may be asymptomatic and the extensive monitoring capabilities of cardiac implantable electronic devices (CIEDs) revealed asymptomatic atrial tachi-arrhythmias of short duration (minutes-hours) occurring in patients with no prior history of AF and without AF detection at a conventional surface ECG. Both the terms "AHRE" (Atrial High-Rate Episodes) and subclinical AF were used in a series of prior studies, that evidenced the association with an increased risk of stroke. Two randomized controlled studies were planned in order to assess the risk-benefit profile of anticoagulation in patients with AHRE/subclinical AF: the NOAH and ARTESiA trials. The results of these two trials (6548 patients enrolled, overall) show that the risk of stroke/systemic embolism associated with AHRE/subclinical AF is in the range of 1-1.2 % per patient-year, but with an important proportion of severe/fatal strokes occurring in non-anticoagulated patients. The apparent discordance between ARTESiA and NOAH results may be approached by considering the related study-level meta-analysis, which highlights a consistent reduction of ischemic stroke with oral anticoagulants vs. aspirin/placebo (relative risk [RR] 0.68, 95 % CI 0.50-0.92). Oral anticoagulation was found to increase major bleeding (RR 1.62, 95 % CI 1.05-2.5), but no difference was found in fatal bleeding (RR 0.79, 95 % CI 0.37-1.69). Additionally, no difference was found in cardiovascular death or all-cause mortality. Taking into account these results, clinical decision-making for patients with AHRE/subclinical AF at risk of stroke, according to CHA2DS2-VASc, can now be evidence-based, considering the benefits and related risks of oral anticoagulants, to be shared with appropriately informed patients.

Clinical decisions for appropriate management of patients with atrial fibrillation.

The management of patients with atrial fibrillation (AF) requires intricate clinical decision-making to optimize outcomes. In everyday clinical practice, physicians undergo difficult choices to better manage patients with AF. They need to balance thromboembolic and bleeding risk to focus on patients' symptoms and to manage a variety of multiple comorbidities. In this review, we aimed to explore the multifaceted dimensions of clinical decision-making in AF patients, encompassing the definition and diagnosis of clinical AF, stroke risk stratification, oral anticoagulant therapy selection, consideration of bleeding risk, and the ongoing debate between rhythm and rate control strategies. We will also focus on possible grey zones for the management of AF patients. In navigating this intricate landscape, clinicians must reconcile the dynamic interplay of patient-specific factors, evolving guidelines, and emerging therapies. The review underscores the need for personalized, evidence-based clinical decision-making to tailor interventions for optimal outcomes according to specific AF patient profiles.

Asymptomatic vs. symptomatic atrial fibrillation: Clinical outcomes in heart failure patients.

BACKGROUND: The outcome implications of asymptomatic vs. symptomatic atrial fibrillation (AF) in specific groups of patients according to clinical heart failure (HF) and left ventricular ejection fraction (LVEF) need to be clarified. METHODS: In a prospective observational study, patients were categorized according to overt HF with LVEF≤40 %, or with LVEF>40 %, or without overt HF with LVEF40 %≤ or > 40 %, as well as according to the presence of asymptomatic or symptomatic AF. RESULTS: A total of 8096 patients, divided into 8 groups according to HF and LVEF, were included with similar proportions of asymptomatic AF (ranging from 43 to 48 %). After a median follow-up of 730 [699 -748] days, the composite outcome (all-cause death and MACE) was significantly worse for patients with asymptomatic AF associated with HF and reduced LVEF vs. symptomatic AF patients of the same group (p = 0.004). On adjusted Cox regression analysis, asymptomatic AF patients with HF and reduced LVEF were independently associated with a higher risk for the composite outcome (aHR 1.32, 95 % CI 1.04-1.69) and all-cause death (aHR 1.33, 95 % CI 1.02-1.73) compared to symptomatic AF patients with HF and reduced LVEF. Kaplan-Meier curves showed that HF-LVEF≤40 % asymptomatic patients had the highest cumulative incidence of all-cause death and MACE (p < 0.001 for both). CONCLUSIONS: In a large European cohort of AF patients, the risk of the composite outcome at 2 years was not different between asymptomatic and symptomatic AF in the whole cohort but adverse implications for poor outcomes were found for asymptomatic AF in HF with LVEF≤40 %.

Comparative analysis of level of evidence and class of recommendation for 50 clinical practice guidelines released by the European Society of Cardiology from 2011 to 2022.

BACKGROUND: The European Society of Cardiology (ESC) clinical practice guidelines are essential tools for decision-making. AIM: To analyze the level of evidence (LOE) and the class of recommendations in the ESC guidelines released in the last 12 years. METHODS: We evaluated 50 ESC guidelines released from 2011 to 2022, related to 27 topics and categorized them into seven macro-groups. We analyzed every recommendation in terms of LOE and class of recommendation, calculating their relative proportions and changes over time in consecutive editions of the same guideline. RESULTS: A total of 6972 recommendations were found, with an increase in number per year over time. Among the 50 ESC guidelines, the proportional distribution of classes of recommendations was 49% for Class I, 29% for Class IIa, 15% for Class IIb, and 8% for Class III. Overall, 16% of the recommendations were classified as LOE A, 31% LOE B and 53% LOE C. The field of preventive cardiology had the largest proportion of LOE A, while the lowest was in the field of valvular, myocardial, pericardial and pulmonary diseases. The overall proportion of LOE A recommendations in the most recent guidelines compared to their prior versions increased from 17% to 20%. CONCLUSIONS: The recommendations included in the ESC guidelines widely differ in terms of quality of evidence, with only 16% supported by the highest quality of evidence. Although a slight global increase in LOE A recommendations was observed in recent years, further scientific research efforts are needed to increase the quality of evidence.

Features of Clinical Complexity in European Patients With Atrial Fibrillation: A Report From a European Observational Prospective AF Registry.

There is increasing concern regarding impact of clinical complexity in patients with atrial fibrillation (AF). We explored the impact of different clinical complexity features in AF patients. We analyzed patients from a prospective, observational, multicenter Europe-wide AF registry. Features of clinical complexity among patients with CHA2DS2-VASc ≥2 were: (1) history of bleeding; (2) frailty; (3) chronic kidney disease (CKD); (4) ≥2 features. A total of 10,169 patients were analyzed. Of these, 141 (1.4%) had history of bleeding, 954 (9.4%) were frail, 1767 (17.4%) had CKD and 1253 (12.3%) had ≥2 features. All features of clinical complexity were less treated with OAC. History of bleeding (HR 1.94, 95% CI 1.32-2.85), frailty (HR 1.38, 95% CI 1.11-1.71), CKD (HR 1.50, 95% 1.28-1.75) and ≥2 features (HR 2.08, 95% CI 1.73-2.51) were associated with outcomes. Presence of features of clinical complexity is associated with lower use of OAC and higher risk of outcomes.

Remote multiparametric monitoring and management of heart failure patients through cardiac implantable electronic devices.

In this review we focus on heart failure (HF) which, as known, is associated with a substantial risk of hospitalizations and adverse cardiovascular outcomes, including death. In recent years, systems to monitor cardiac function and patient parameters have been developed with the aim to detect subclinical pathophysiological changes that precede worsening HF. Several patient-specific parameters can be remotely monitored through cardiac implantable electronic devices (CIED) and can be combined in multiparametric scores predicting patients' risk of worsening HF with good sensitivity and moderate specificity. Early patient management at the time of pre-clinical alerts remotely transmitted by CIEDs to physicians might prevent hospitalizations. However, it is not clear yet which is the best diagnostic pathway for HF patients after a CIED alert, which kind of medications should be changed or escalated, and in which case in-hospital visits or in-hospital admissions are required. Finally, the specific role of healthcare professionals involved in HF patient management under remote monitoring is still matter of definition. We analyzed recent data on multiparametric monitoring of patients with HF through CIEDs. We provided practical insights on how to timely manage CIED alarms with the aim to prevent worsening HF. We also discussed the role of biomarkers and thoracic echo in this context, and potential organizational models including multidisciplinary teams for remote care of HF patients with CIEDs.

Cardiac Surgery in Jehovah's Witnesses Patients and Association With Peri-Operative Outcomes: A Systematic Review and Meta-Analysis.

BACKGROUND: Strategies for blood conservation, coupled with a careful preoperative assessment, may be applied to Jehovah's Witnesses (JW) patients who are candidates for cardiac surgery interventions. There is a need to assess clinical outcomes and safety of bloodless surgery in JW patients undergoing cardiac surgery. METHODS: We performed a systematic review and meta-analysis of studies comparing JW patients with controls undergoing cardiac surgery. The primary endpoint was short-term mortality (in-hospital or 30-day mortality). Peri-procedural myocardial infarction, re-exploration for bleeding, pre-and postoperative Hb levels and cardiopulmonary bypass (CPB) time were also analyzed. RESULTS: A total of 10 studies including 2,302 patients were included. The pooled analysis showed no substantial differences in terms of short-term mortality among the two groups (OR 1.13, 95% CI 0.74-1.73, I2=0%). There were no differences in peri-operative outcomes among JW patients and controls (OR 0.97, 95% CI 0.39-2.41, I2=18% for myocardial infarction; OR 0.80, 95% CI 0.51-1.25, I2=0% for re-exploration for bleeding). JW patients had a higher level of preoperative Hb (Standardized Mean Difference [SMD] 0.32, 95% CI 0.06-0.57) and a trend toward a higher level of postoperative Hb (SMD 0.44, 95% CI -0.01-0.90). A slightly lower CPB time emerged in JWs compared with controls (SMD -0.11, 95% CI -0.30-0.07). CONCLUSIONS: JW patients undergoing cardiac surgery, with avoidance of blood transfusions, did not have substantially different peri-operative outcomes compared with controls, with specific reference to mortality, myocardial infarction, and re-exploration for bleeding. Our results support the safety and feasibility of bloodless cardiac surgery, applying patient blood management strategies.

Atrial cardiomyopathy: An entity of emerging interest in the clinical setting.

Since 1995, the concept of atrial cardiomyopathy (ACM) has been associated with myocardial fibrosis. Despite a consensus document in 2016, ACM's definition primarily relies on histopathological findings. The focus on diagnostic criteria for ACM is driven by the potential link to thromboembolic events even independently on atrial fibrillation (AF). The complexity of the mutual relationships between ACM and AF makes difficult any assessment of the thromboembolic risk associated to ACM per se. ACM's thrombogenicity is a multifaceted clinical phenomenon involving electrical, functional, and structural modifications. Factors such as cardiovascular risk factors (e.g., hypertension), common cardiac comorbidities (e.g., heart failure), and extracardiac conditions (e.g., neuromuscular disorders) can promote atrial derangement, triggering atrial fibrillation (AF) and increasing the risk of thromboembolic events. Several diagnostic methods are available to detect the key features of ACM, including electrical changes assessed by surface and intracavitary ECG, and structural and functional alterations evaluated through echocardiography and cardiac magnetic resonance (CMR). These methods can be complemented by electro-anatomical mapping (EAM) to enhance the accuracy of myocardial tissue characterization and assessment of atrial fibrosis. Although certain clinical conditions (e.g., atrial high-rate episodes, AHREs; embolic stroke of undetermined source, ESUS) often exhibit atrial alterations in their thromboembolic presentations, recent randomized trials have failed to demonstrate the benefits of oral anticoagulation in patients with ACM without AF. However, ACM constitutes the substrate for the development of AF, as proposed in the AF European guidelines under the 4S-AF scheme. This review emphasizes the lack of a diagnostic gold standard and the need for clinical criteria for ACM, aiming to better understand the potential therapeutic implications of atrial structural and functional derangements, even in the absence of clinical evidence of AF.

Quantification of Myocardial Contraction Fraction with Three-Dimensional Automated, Machine-Learning-Based Left-Heart-Chamber Metrics: Diagnostic Utility in Hypertrophic Phenotypes and Normal Ejection Fraction.

Aims: The differentiation of left ventricular (LV) hypertrophic phenotypes is challenging in patients with normal ejection fraction (EF). The myocardial contraction fraction (MCF) is a simple dimensionless index useful for specifically identifying cardiac amyloidosis (CA) and hypertrophic cardiomyopathy (HCM) when calculated by cardiac magnetic resonance. The purpose of this study was to evaluate the value of MCF measured by three-dimensional automated, machine-learning-based LV chamber metrics (dynamic heart model [DHM]) for the discrimination of different forms of hypertrophic phenotypes. Methods and Results: We analyzed the DHM LV metrics of patients with CA (n = 10), hypertrophic cardiomyopathy (HCM, n = 36), isolated hypertension (IH, n = 87), and 54 healthy controls. MCF was calculated by dividing LV stroke volume by LV myocardial volume. Compared with controls (median 61.95%, interquartile range 55.43-67.79%), mean values for MCF were significantly reduced in HCM-48.55% (43.46-54.86% p < 0.001)-and CA-40.92% (36.68-46.84% p < 0.002)-but not in IH-59.35% (53.22-64.93% p < 0.7). MCF showed a weak correlation with EF in the overall cohort (R2 = 0.136) and the four study subgroups (healthy adults, R2 = 0.039 IH, R2 = 0.089; HCM, R2 = 0.225; CA, R2 = 0.102). ROC analyses showed that MCF could differentiate between healthy adults and HCM (sensitivity 75.9%, specificity 77.8%, AUC 0.814) and between healthy adults and CA (sensitivity 87.0%, specificity 100%, AUC 0.959). The best cut-off values were 55.3% and 52.8%. Conclusions: The easily derived quantification of MCF by DHM can refine our echocardiographic discrimination capacity in patients with hypertrophic phenotype and normal EF. It should be added to the diagnostic workup of these patients.

Cardiovascular Reasons for Access to a Tertiary Oncological Emergency Service: The CARILLON Study.

BACKGROUND: The prevalence of acute cardiovascular diseases (CVDs) in cancer patients is steadily increasing and represents a significant reason for admission to the emergency department (ED). METHODS: We conducted a prospective observational study, enrolling consecutive patients with cancer presenting to a tertiary oncological ED and consequently admitted to the oncology ward. Two groups of patients were identified based on main symptoms that lead to ED presentation: symptoms potentially related to CVD vs. symptoms potentially not related to CVD. The aims of the study were to describe the prevalence of symptoms potentially related to CVD in this specific setting and to evaluate the prevalence of definite CV diagnoses at discharge. Secondary endpoints were new intercurrent in-hospital CV events occurrence, length of stay in the oncology ward, and mid-term mortality for all-cause. RESULTS: A total of 469 patients (51.8% female, median age 68.0 [59.1-76.3]) were enrolled. One hundred and eighty-six out of 469 (39.7%) presented to the ED with symptoms potentially related to CVD. Baseline characteristics were substantially similar between the two study groups. A discharge diagnosis of CVD was confirmed in 24/186 (12.9%) patients presenting with symptoms potentially related to CVD and in no patients presenting without symptoms potentially related to CVD (p < 0.01). During a median follow-up of 3.4 (1.2-6.5) months, 204 (43.5%) patients died (incidence rate of 10.1 per 100 person/months). No differences were found between study groups in terms of all-cause mortality (hazard ratio [HR]: 0.85, 95% confidence interval [CI] 0.64-1.12), new in-hospital CV events (HR: 1.03, 95% CI 0.77-1.37), and length of stay (p = 0.57). CONCLUSIONS: In a contemporary cohort of cancer patients presenting to a tertiary oncological ED and admitted to an oncology ward, symptoms potentially related to CVD were present in around 40% of patients, but only a minority were actually diagnosed with an acute CVD.

Atrial fibrillation in vascular surgery: a systematic review and meta-analysis on prevalence, incidence and outcome implications.

AIMS: To know the prevalence of atrial fibrillation (AF), as well as the incidence of postoperative AF (POAF) in vascular surgery for arterial diseases and its outcome implications. METHODS: We performed a systematic review and meta-analysis following the PRISMA statement. RESULTS: After the selection process, we analyzed 44 records (30 for the prevalence of AF history and 14 for the incidence of POAF).The prevalence of history of AF was 11.5% [95% confidence interval (CI) 1-13.3] with high heterogeneity (I2 = 100%). Prevalence was higher in the case of endovascular procedures. History of AF was associated with a worse outcome in terms of in-hospital death [odds ratio (OR) 3.29; 95% CI 2.66-4.06; P < 0.0001; I2 94%] or stroke (OR 1.61; 95% CI 1.39-1.86; P < 0.0001; I2 91%).The pooled incidence of POAF was 3.6% (95% CI 2-6.4) with high heterogeneity (I2 = 100%). POAF risk was associated with older age (mean difference 4.67 years, 95% CI 2.38-6.96; P = 0.00007). The risk of POAF was lower in patients treated with endovascular procedures as compared with an open surgical procedure (OR 0.35; 95% CI 0.13-0.91; P = 0.03; I2 = 61%). CONCLUSIONS: In the setting of vascular surgery for arterial diseases a history of AF is found overall in 11.5% of patients, more frequently in the case of endovascular procedures, and is associated with worse outcomes in terms of short-term mortality and stroke.The incidence of POAF is overall 3.6%, and is lower in patients treated with an endovascular procedure as compared with open surgery procedures. The need for oral anticoagulants for preventing AF-related stroke should be evaluated with randomized clinical trials.

Factors Associated with Progression of Atrial Fibrillation and Impact on All-Cause Mortality in a Cohort of European Patients.

BACKGROUND: Paroxysmal atrial fibrillation (AF) may often progress towards more sustained forms of the arrhythmia, but further research is needed on the factors associated with this clinical course. METHODS: We analyzed patients enrolled in a prospective cohort study of AF patients. Patients with paroxysmal AF at baseline or first-detected AF (with successful cardioversion) were included. According to rhythm status at 1 year, patients were stratified into: (i) No AF progression and (ii) AF progression. All-cause death was the primary outcome. RESULTS: A total of 2688 patients were included (median age 67 years, interquartile range 60-75, females 44.7%). At 1-year of follow-up, 2094 (77.9%) patients showed no AF progression, while 594 (22.1%) developed persistent or permanent AF. On multivariable logistic regression analysis, no physical activity (odds ratio [OR] 1.35, 95% CI 1.02-1.78), valvular heart disease (OR 1.63, 95% CI 1.23-2.15), left atrial diameter (OR 1.03, 95% CI 1.01-1.05), or left ventricular ejection fraction (OR 0.98, 95% CI 0.97-1.00) were independently associated with AF progression at 1 year. After the assessment at 1 year, the patients were followed for an extended follow-up of 371 days, and those with AF progression were independently associated with a higher risk for all-cause death (adjusted hazard ratio 1.77, 95% CI 1.09-2.89) compared to no-AF-progression patients. CONCLUSIONS: In a contemporary cohort of AF patients, a substantial proportion of patients presenting with paroxysmal or first-detected AF showed progression of the AF pattern within 1 year, and clinical factors related to cardiac remodeling were associated with progression. AF progression was associated with an increased risk of all-cause mortality.