Multimodal assessment of electrical and structural atrial remodeling identifies a subgroup of ESUS patients with an increased risk of adverse events and may support further evaluation in future rhythm-guided or anticoagulation studies.
Abstract
Background Embolic stroke of undetermined source (ESUS) carries a substantial recurrence risk, yet anticoagulation has not proven superior to antiplatelet therapy in unselected patients. Atrial cardiomyopathy, reflecting electrical and structural atrial remodeling, may identify a high-risk ESUS subgroup. Objectives The purpose of this study was to characterize the extent of electrical and structural atrial remodeling in patients with ESUS and to evaluate its association with adverse cardiovascular outcomes during follow-up. Methods In this prospective single-center study, 103 consecutive ESUS patients and 123 age- and sex-matched controls without known cardiac disease underwent clinical evaluation, NT-proBNP measurement, 12-lead electrocardiogram, and transthoracic echocardiography. Patients were followed for ≥12 months. The primary endpoint was a composite of all-cause death, recurrent stroke, transient ischemic attack, myocardial infarction, or newly diagnosed atrial fibrillation. Independent predictors were determined using multivariable Cox regression. Results ESUS patients exhibited higher NT-proBNP, more frequent advanced interatrial block, and impaired left atrial function compared with controls. Over a median follow-up of 382 days (IQR: 366-697 days), 29 ESUS patients (29/103, 28%) reached the primary endpoint. Independent predictors were NT-proBNP >420 pg/mL, advanced interatrial block, E′ ≤9 cm/s, left atrial volume index ≥29 mL/m2, and left atrial ejection fraction <50%. A risk score integrating ≥3 markers identified a subgroup with markedly increased risk, in whom Kaplan-Meier estimated event-free survival at 1 year was approximately 50% (95% CI: 31.6%-68.4%). Conclusions Multimodal assessment of electrical and structural atrial remodeling identifies a subgroup of ESUS patients with an increased risk of adverse events. These findings underscore the potential clinical relevance of atrial cardiomyopathy and may support further evaluation in future rhythm-guided or anticoagulation studies.
Background: Atrial fibrillation detected after stroke (AFDAS) is frequently diagnosed after embolic stroke of undetermined source (ESUS) and has important implications for secondary stroke prevention. Although prediction scores have been proposed to identify patients at increased risk of AFDAS, prospective evidence supporting their implementation to guide rhythm monitoring in routine clinical practice is limited. Methods: In this prospective, population-based implementation cohort study, adults with ESUS were enrolled between January 2022 and December 2024 across all stroke centers in Styria, Austria. The Graz AF Risk Score was prospectively implemented as part of a risk-adapted diagnostic pathway for cardiac rhythm monitoring. Patients with a score [≥]4 were recommended for implantable loop recorder monitoring, whereas monitoring in those with scores <4 remained at the treating physician's discretion. The primary outcome was AFDAS detection; recurrent ischemic stroke and recurrent stroke etiology were secondary outcomes. Results: Among 784 patients (median age 73 years [IQR 64-80], 45.7% women), AFDAS was detected in 166 patients (21.2%) during a median follow-up of 26.3 months (IQR 20-34). AFDAS detection was substantially higher in patients with a Graz AF Risk Score [≥]4 than <4 (38.1% vs. 3.9%; p<0.001). After adjustment for age, sex and ILR monitoring, a score [≥]4 independently predicted AFDAS (HR 6.3, 95% CI 3.5-11.2; p<0.001) and recurrent ischemic stroke (HR 2.2, 95% CI 1.1-4.1; p=0.023). Only one recurrent stroke in patients with a score <4 was attributable to atrial fibrillation (AF) (1/18, 5.6%). Conclusions: Prospective implementation of the Graz AF Risk Score identified patients with ESUS at markedly different risks of AFDAS. A Graz AF Risk Score [≥]4 was also independently associated with recurrent ischemic stroke. These findings support a risk-adapted approach to cardiac rhythm monitoring after ESUS.
J. Elbischger, A. Krainer, T. Ruprechter et al.· medRxiv· 0 citations
Atrial and ventricular ectopy are frequently encountered during ambulatory monitoring in asymptomatic adults; however, their independent long-term prognostic significance in low-risk populations without structural heart disease remains a subject of ongoing clinical debate.
To identify the distinct clinical and physiological determinants of atrial ectopic burden (AEB) and ventricular ectopic burden (VEB), and to evaluate their independent long-term associations with major adverse cardiovascular events (MACE) in a primary prevention cohort.
We evaluated 931 asymptomatic individuals (mean age 52 ± 7 years; 13% female) without structural heart disease who completed a baseline 24-hour Holter recording. High AEB and VEB were defined using cohort-specific medians and/or the presence of ambulatory arrhythmic complexity. Complete longitudinal tracking for MACE (composite of acute coronary syndrome, cerebrovascular accident, new-onset heart failure or cardiovascular mortality) was available for 840 participants over a median follow-up of 8 years (IQR 5-11 years). To evaluate the robustness of the atrial findings, a prespecified sensitivity analysis was performed by excluding patients with baseline atrial fibrillation (AF).
Over the follow-up period, the primary MACE endpoint occurred in 149 (18%) participants. In multivariable logistic regression models, high AEB was independently driven by older age (OR 1.09, 95% CI 1.06-1.12; p < 0.001), male sex (OR 1.60, 95% CI 1.02-2.52; p = 0.042), reduced eGFR (OR 0.98, 95% CI 0.97-0.99; p = 0.049), and low cardiorespiratory fitness (OR 1.38, 95% CI 1.01-1.92; p = 0.049). Conversely, high VEB was independently associated only with older age (OR 1.04, 95% CI 1.02-1.07; p < 0.001) and reduced eGFR (OR 0.98, 95% CI 0.97-0.99; p = 0.034). In fully adjusted multivariable Cox proportional hazards models, high VEB remained a robust independent predictor of MACE, conferring a three-fold increase in risk (HR 3.06, 95% CI 2.06-4.56; p < 0.001). In tertile-based analyses of pure ectopic burden, increasing VEB demonstrated a robust graded association with MACE after adjustment for age, sex, beta-blocker use and antiarrhythmic drug therapy (HR per tertile increase 2.02, 95% CI 1.60-2.53; p < 0.001), whereas AEB showed only a borderline association that did not reach statistical significance (HR per tertile increase 1.21, 95% CI 0.98-1.50; p = 0.076).
In asymptomatic adults without structural heart disease, the clinical determinants and long-term prognostic trajectories of ectopy exhibit a profound chamber-specific divergence. Ventricular ectopic burden stands out as a powerful, independent marker of intrinsic electrical vulnerability and long-term cardiovascular risk. Meanwhile, atrial ectopy is highly sensitive to systemic physiological fitness and carries a weaker prognostic signal that attenuates completely upon multivariate clinical and medication adjustment.
A. Moses, R. Givoli Vilensky, N. Makmal et al.· European Heart Journal Open· 0 citations
Embolic stroke of undetermined source (ESUS) accounts for approximately one-third of all ischemic strokes. Atrial cardiomyopathy, independent of paroxysmal atrial fibrillation, is an increasingly recognized embolic substrate. Left atrial (LA) strain assessed by speckle-tracking echocardiography or cardiac magnetic resonance provides a sensitive, noninvasive measure of subclinical atrial mechanical dysfunction that precedes chamber enlargement. This systematic review and meta-analysis synthesizes evidence on all 3 LA strain phases in ESUS through July 2026. Seven studies met the inclusion criteria; 5 provided extractable quantitative data for meta-analysis (n = 656, n = 40, n = 56, n = 82, and n = 459; total N = 1293). ESUS patients demonstrated significantly reduced LA reservoir strain [mean difference (MD) = -4.43%, 95% confidence interval (CI), -6.77 to -2.09; I2 = 82.25%; P = 0.0002], LA conduit strain (LAScd) (MD = -1.69%, 95% CI, -2.20 to -1.18; I2 = 0.00%; P < 0.0001), and LA contractile strain (MD = -2.24%, 95% CI, -3.34 to -1.14; I2 = 69.92%; P < 0.0001). LAScd I2 = 0.00% indicates remarkably consistent conduit impairment across all 5 studies. All 5 meta-analytic studies achieved a Newcastle-Ottawa Scale score of ≥7. All 3 LA strain phases are consistently and significantly impaired in ESUS patients versus controls. Near-zero LAScd heterogeneity identifies conduit strain as the most reproducible marker of atrial cardiomyopathy in ESUS. These findings support subclinical atrial cardiomyopathy as an embolic substrate independent of atrial fibrillation. Large, prospective, standardized multicenter studies are required before clinical translation.
Unknown authors· Cardiology in Review· 0 citations
BACKGROUND
Atrial fibrillation (AF) is pervasive and an independent driver of stroke and death in hypertrophic cardiomyopathy (HCM). Despite guideline recommendations for AF surveillance, effective risk stratification remains elusive, and the hemodynamic and functional states of the left atrium (LA) preceding AF onset remain poorly characterized.
OBJECTIVES
We aimed to delineate the hemodynamic and functional states of the LA in HCM, derive a novel LA staging system, and evaluate its prognostic performance for new-onset atrial fibrillation (NOAF).
METHODS
This multicenter retrospective study included consecutive HCM patients with normal left ventricular systolic function from January 2007 to February 2024 at 2 academic referral centers. Patients with valvular heart disease or prior AF were excluded. Patients were categorized by combining the presence of elevated LA pressure (hemodynamic load) and LA contractile strain (intrinsic LA function): stage 1 (normal LA pressure and function), stage 2 (relative contractile augmentation for a given LA pressure), stage 3 (loss of relative contractile augmentation despite elevated LA pressure), stage 4 (elevated LA pressure with decreased LA contractile strain), and isolated LA contractile dysfunction. The primary outcome was NOAF. External validation was conducted in an independent HCM cohort.
RESULTS
Of 1,856 patients screened, 705 were eligible (mean age 57.6 ± 13.0 years, 30.1% female). During a median follow-up of 7.5 years (Q1-Q3: 3.6-11.0 years), NOAF occurred in 101. The staging system was independently associated with a significant, stepwise increase in the risk of NOAF (adjusted HR: 1.83 per increment; 95% CI: 1.42-2.37; P < 0.001) and conferred incremental predictive value beyond established risk models (CHARGE-AF and HCM-AF). Consistent results were demonstrated in 1-year landmark and competing-risk analyses, as well as in an external validation cohort (n = 425; age 59.7 ± 13.5 years, 33.9% female). Importantly, serial echocardiography performed in 217 patients 4 to 6 years after baseline revealed a predominantly unidirectional evolution of the proposed LA stage, with most patients remaining stable (39.6%) or progressing to higher stages or AF (43.8%).
CONCLUSIONS
The proposed LA staging framework offers mechanistic insights into how the LA adapts to progressive diastolic dysfunction in HCM. It is associated with a graded risk of NOAF and may help tailor AF surveillance strategies.
Jaehyun Lim, I. Hwang, Ji-Hyun Kim et al.· Journal of the American Coll...· 0 citations
Cardioembolic stroke remains one of the most severe complications of atrial fibrillation (AF), particularly in patients with structural heart disease such as mitral stenosis (MS). Moderate-to-severe MS contributes to left atrial enlargement and blood stasis, thereby increasing the risk of thromboembolism even in the absence of visible intracardiac thrombus on imaging.1,2 Early identification of underlying valvular abnormalities in patients presenting with ischemic stroke is essential for optimizing secondary prevention.3 A 40-year-old woman was referred to a tertiary healthcare facility for echocardiographic evaluation following hospitalization for suspected nonhemorrhagic stroke associated with atrial fibrillation and a urinary tract infection. She initially presented with dysarthria, aphasia, and dysphagia. Physical examination revealed stable hemodynamics with central cranial nerve VII and XI paresis. Electrocardiography demonstrated atrial fibrillation with a controlled ventricular response. Brain computed tomography showed infarction in the left frontal lobe and left corona radiata, with additional lacunar infarcts in the midbrain and pons. Transthoracic echocardiography revealed moderate mitral stenosis with a mitral valve area of 1.44 cm², mild mitral regurgitation, left atrial dilation, mildly reduced left ventricular systolic function, reduced right ventricular systolic function, and minimal pericardial effusion, without evidence of intracardiac thrombus or vegetation. The patient received multidisciplinary management involving neurologists and cardiologists, including antiplatelet therapy, a beta-blocker, a statin, diuretics, and supportive care, resulting in gradual neurological improvement. This case highlights ischemic stroke as the first clinical manifestation of previously undiagnosed moderate mitral stenosis accompanied by atrial fibrillation. The coexistence of AF and left atrial enlargement likely contributed to the cardioembolic risk despite the absence of a demonstrable intracardiac thrombus.
Unknown authors· Jurnal Indonesia Sosial Sain...· 0 citations
The CHA2DS2-VALa score significantly improves stroke risk stratification in AF by integrating LA diameter into conventional scoring, as echocardiographic measurement is widely available and reproducible.
Sefa Erdi Ömür, Emin Koyun, Gülşen Genç Tapar et al.· Cardiovascular Electrophysio...· 0 citations
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