The Atrial Fibrillation and Heart Failure with Preserved Ejection Fraction "Twindemic" - Shared Root Causes and Treatment Targets.

Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) are comorbid conditions that are increasingly prevalent and have a high socioeconomic burden. This article discusses their shared pathophysiology, focusing on the triad of hypertension, obesity, and aging. We highlight the misperception that pharmacologic heart rate lowering is beneficial, which has resulted in an overprescription of beta-blockers in HFpEF and AF. In contrast, heart rate modulation through accelerated pacing provides hemodynamic and structural advantages, which have yielded significant improvements in quality of life, physical activity, and AF burden in the myPACE trial of patients with preclinical or overt HFpEF.

Association of central arterial stiffness with atrial myopathy: the Atherosclerosis Risk in Communities (ARIC) study.

Atrial myopathy-defined as abnormal left atrial (LA) size and function-is associated with an increased risk of atrial fibrillation, heart failure, and dementia. Central arterial stiffness is associated with increased atrial afterload and fibrosis and may be a risk factor for atrial myopathy. We examined the association of carotid-femoral pulse wave velocity (cfPWV) with LA function and assessed potential causal relationships. We included 2825 Atherosclerosis Risk in Communities (ARIC) study participants from Visit 5 (2011-2013). cfPWV was related to echocardiographic LA function continuously per 1-SD and categorically in quartiles. Mendelian randomization (MR) analysis was performed using U.K. Biobank-derived genetic variants associated with arterial stiffness index and cardiac magnetic resonance measures of LA function. When analyzed per SD increment (297.6 cm/s), higher cfPWV was significantly associated with lower LA reservoir and conduit strain (ß = -0.53%, 95% CI [-0.81, -0.25] and ß = -0.46%, 95% CI [-0.68, -0.25], respectively) after adjusting for demographics, clinical characteristics, systolic blood pressure, and left ventricular (LV) morphology and function. In MR analyses there was a non-significant inverse association of arterial stiffness index with LA total, passive, and active emptying fractions. Higher cfPWV is associated with lower LA reservoir and conduit strain, independent of systolic blood pressure and LV morphology and function. No evidence for a causal relationship between arterial stiffness index and alterations in LA function was found. Future studies should examine the prospective association of central arterial stiffness with LA function alterations.

Diagnostic and prognostic value of the left atrial myopathy evaluation in cardiac amyloidosis using echocardiography.

BACKGROUND: Cardiac amyloidosis (CA) is an under-recognized cause of heart failure. Left atrial (LA) myopathy contributes to a worse prognosis in heart failure and is a feature of transthyretin (ATTR) and light-chain (AL) CA. LA mechanical dispersion (LA-MD) is a novel marker of intra-atrial dyssynchrony implicated in LA myopathy and the future development of atrial fibrillation (AF). AIMS: This study aimed to determine the characteristics and prognostic value of LA myopathy in ATTR and AL cardiomyopathy through a comprehensive LA echocardiographic evaluation. METHODS: ATTR (n = 86) and AL (n = 86) CA patients were compared with hypertensive heart disease (HHT) patients (n = 58). Transthoracic echocardiographic measurements including LA strain and LA-MD were obtained with patient follow-up for mortality. RESULTS: ATTR and AL patients had a median follow-up of 66 months, with 26 mortality events. Left ventricular (LV) mass, diastolic function (average-e' and E/e'), LV global longitudinal strain, and LA volume and function (LA function index and strain) were more impaired in ATTR versus AL; these echocardiographic parameters were more impaired in both amyloid groups compared to HHT patients (P < 0.05). LA-MD was increased in ATTR versus AL [median 72.2 (inter-quartile range 55-88.9) vs. 54 (43.5-64.2), respectively, P < 0.001]. Multivariable logistic regression adjusted for age, presence of AF, LV mass, global and basal strain, and E/e' demonstrated that LA-MD was an independent determinant of ATTR CA (P = 0.014). On multivariable analysis, LA reservoir strain was independently associated with the presence of heart failure in the CA group (P < 0.001). LA minimum volume (cut-off ≥18 mL/m2) was a determinant of mortality in AL CA [Cox proportional hazard ratio (HR) 1.042 (1.003-1.082), P = 0.034 and Kaplan-Meier analysis, P = 0.016]. CONCLUSION: Characterizing LA myopathy has significant diagnostic and prognostic utility in CA. ATTR patients have increased atrial dyssynchrony, which may have implications for AF development. LA reservoir strain was associated with heart failure in CA, whilst LA minimum volume was a predictor of mortality in AL CA.

Atrial cardiopathy biomarkers and atrial fibrillation in the ARCADIA trial.

BACKGROUND: ARCADIA compared apixaban to aspirin for secondary stroke prevention in patients with cryptogenic stroke and atrial cardiopathy. One possible explanation for the neutral result is that biomarkers used did not optimally identify atrial cardiopathy. We examined the relationship between biomarker levels and subsequent detection of AF, the hallmark of atrial cardiopathy. METHODS: Patients were randomized if they met criteria for atrial cardiopathy, defined as P-wave terminal force >5000 µV*ms in ECG lead V1 (PTFV1), NT-proBNP >250 pg/mL, or left atrial diameter index (LADI) ⩾3 cm/m2. For this analysis, the outcome was AF detected per routine care. RESULTS: Of 3745 patients who consented to screening for atrial cardiopathy, 254 were subsequently diagnosed with AF; 96 before they could be randomized and 158 after randomization. In unadjusted analyses, ln(NT-proBNP) (RR per SD, 1.99; 95% CI, 1.85-2.13), PTFV1 (RR per SD, 1.15; 95% CI, 1.03-1.28) and LADI (RR per SD, 1.34; 95% CI, 1.20-1.50) were associated with AF. In a model containing all 3 biomarkers, demographics, and AF risk factors, age (RR per 10 years, 1.24; 95% CI, 1.09-1.41), ln(NT-proBNP) (RR per SD, 1.88; 95% CI, 1.67-2.11) and LADI (RR per SD, 1.25; 95% CI, 1.14-1.37) were associated with AF. These three variables together had a c-statistic of 0.82 (95% CI, 0.79-0.85) but only modest calibration. Discrimination was attenuated in sensitivity analyses of patients eligible for randomization who may have been more closely followed for AF. CONCLUSIONS: Biomarkers used to identify atrial cardiopathy in ARCADIA were moderately predictive of subsequent AF.

Atrial Fibrillation, Atrial Myopathy, and Thromboembolism: The Additive Value of Echocardiography and Possible New Horizons for Risk Stratification.

Atrial fibrillation (AF) is the most common cardiac sustained arrhythmia, and it is associated with increased stroke and dementia risk. While the established paradigm attributes these complications to blood stasis within the atria and subsequent thrombus formation with cerebral embolization, recent evidence suggests that atrial myopathy (AM) may play a key role. AM is characterized by structural and functional abnormalities of the atria, and can occur with or without AF. Moving beyond classifications based solely on episode duration, the 4S-AF characterization has offered a more comprehensive approach, incorporating patient's stroke risk, symptom severity, AF burden, and substrate assessment (including AM) for tailored treatment decisions. The "ABC" pathway emphasizes anticoagulation, symptom control, and cardiovascular risk modification and emerging evidence suggests broader benefits of early rhythm control strategies, potentially reducing stroke and dementia risk and improving clinical outcomes. However, a better integration of AM assessment into the current framework holds promise for further personalizing AF management and optimizing patient outcomes. This review explores the emerging concept of AM and its potential role as a risk factor for stroke and dementia and in AF patients' management strategies, highlighting the limitations of current risk stratification methods, like the CHA2DS2-VASc score. Echocardiography, particularly left atrial (LA) strain analysis, has shown to be a promising non-invasive tool for AM evaluation and recent studies suggest that LA strain analysis may be a more sensitive risk stratifier for thromboembolic events than AF itself, with some studies showing a stronger association between LA strain and thromboembolic events compared to traditional risk factors. Integrating it into routine clinical practice could improve patient management and targeted therapies for AF and potentially other thromboembolic events. Future studies are needed to explore the efficacy and safety of anticoagulation in AM patients with and without AF and to refine the diagnostic criteria for AM.

Left atrial low voltage areas and heart failure in patients with atrial fibrillation: Implication of the atrial myopathy.

AIMS: Atrial fibrillation (AF) and heart failure (HF) affect each other and are often co-morbid. The fact that HF development is not uncommon even after ablation suggests that we need a deeper understanding of the pathology of these conditions. Atrial myocardial degeneration is an underlying factor in AF patients and may be associated with HF development after ablation. This study aimed to investigate the impact of low-voltage areas (LVAs) on HF prognosis after AF ablation. METHODS AND RESULTS: This observational study included 1481 consecutive patients undergoing initial ablation for AF. Left atrial LVAs were defined as regions with a bipolar peak-to-peak voltage of <0.50 mV. Patients were divided into three groups: no LVA (LVA size indexed to body surface area <3 cm2/m2, n = 1129), small LVA (3-10 cm2/m2, n = 217), and extensive LVA (≥10 cm2/m2, n = 135). A composite endpoint of HF hospitalization or death occurred more frequently in patients with larger LVAs (3.3% vs. 6.5% vs. 13.3%, P < 0.0001) during the 3-year follow up period. The extent of LVAs was independently related to the risk of the composite endpoint with an adjusted hazard ratio of 1.55 (95% confidence interval, 1.16-2.10) for each additional step of LVA classification (P = 0.003). CONCLUSIONS: LVA presence and its extent were associated with frequent HF hospitalization and death. Underlying atrial myopathy appears to define a poor HF prognosis after AF ablation.

Inflammatory-mediated atrial cardiomyopathy diagnosed using multimodality imaging and successfully treated with prednisolone: a case report.

Background: Atrial fibrillation is a common cardiac arrhythmia and often develops secondary to structural cardiac changes. Both the occurrence of atrial fibrillation and/or structural changes of the heart may lead to development of atrial cardiomyopathy and heart failure (HF). However, isolated atrial cardiomyopathy caused by focal atrial thickening is a rare condition, previously only described in case reports as a result of different aetiologies all linked to inflammation. Case summary: A patient with inflammatory-mediated atrial cardiomyopathy causing atrial fibrillation and acute decompensated HF presented as isolated left atrial wall thickening on transoesophageal echocardiography. The diagnosis was confirmed using multimodality imaging with transthoracic and transoesophageal echocardiography, cardiac magnetic resonance imaging, positron emissions tomography/computer tomography scanning and intracardiac echocardiography-guided endomyocardial biopsy. Despite no specific histological aetiology, the observed atrial cardiomyopathy might be associated with type 1 diabetes mellitus. The patient in the present case was successfully treated with prednisolone. Discussion: Diabetes mellitus is an important risk factor for developing atrial fibrillation and diabetic cardiomyopathy, due to reduced levels of anti-inflammatory and increased levels of proinflammatory cytokines causing cardiac inflammatory structural remodelling. The regression of the atrial thickening might be due to prednisolone's anti-inflammatory effects and thereby ability to suppress atrial remodelling and reduce the occurrence of atrial fibrillation. However, the effect of prednisolone might only affect the non-manifested inflammatory-mediated atrial remodelling. Due to the rare occurrence of isolated atrial cardiomyopathy a multiple imaging approach during the diagnostic process and follow-ups are essential to determine the aetiology and effect of the treatment.

Characterization of patients with extensive left atrial myopathy referred for atrial fibrillation ablation: incidence, predictors, and outcomes.

BACKGROUND: Although atrial fibrosis has a relevant impact on ablation success rate, experimental studies have reported that extensive fibrosis may be accompanied by a reduced burden secondary to a prominent depression of atrial excitability. OBJECTIVES: We aimed to identify clinical and echocardiographic factors associated with extensive left atrial myopathy (ELAM), to analyze the predictive ability of established scores (AF score, APPLE, and DR-FLASH) and assess outcomes in terms of AF recurrence, left atrial flutter, and post-procedural heart failure admissions. METHODS: A total of 950 consecutive patients undergoing the first AF ablation were included. A 3D electroanatomical mapping system (CARTO3, Biosense Webster) was created using a multipolar mapping catheter (PentaRay, Biosense Webster). ELAM was defined as ≥ 50% low voltage area. A subanalysis with four groups was also created (< 10%; 10-20%; 10-20%; and > 30%). Logistic regressions, Cox proportional hazards models, and log-rank test were used to test the predictors independently associated with the presence of ELAM and AF recurrence. The model was prospectively validated in a cohort of 150 patients obtaining an excellent ability for prediction AUC 0.90 (CI 95% 0.84-0.96). RESULTS: Overall, 78 (8.42%) presented ELAM. Age, female sex, persistent AF, first-degree AV block, and E/e' were significant predictors. The model incorporating these factors outperformed the existing scores (AUC = 0.87). During a mean follow-up of 20 months (IQR 9 to 36), patients with ELAM presented a higher rate of AF recurrence (42.02% vs 26.01%, p = 0.030), left atrial flutter (26.03% vs 8.02%, p < 0.001), and post-procedural heart failure admissions (12.01% vs 0.61%, p < 0.001) than non-ELAM patients. CONCLUSIONS: This study reveals the incidence and clinical factors associated with ELAM in AF, highlighting age, female, persistent AF, first-degree AV block, and E/e'. Importantly, the presence of ELAM is associated with poorer outcomes in terms of recurrence and HF admission.

Development and validation of the Atri-Risk Conduction Index risk score to predict risk of atrial fibrillation after typical atrial flutter ablation.

BACKGROUND: Identification of patients at risk for atrial fibrillation (AF) after typical atrial flutter (tAFL) ablation is important to guide monitoring and treatment. OBJECTIVE: The purpose of this study was to create and validate a risk score to predict AF after tAFL ablation METHODS: We identified patients who underwent tAFL ablation with no AF history between 2017 and 2022 and randomly allocated to derivation and validation cohorts. We collected clinical variables and measured conduction parameters in sinus rhythm on an electrophysiology recording system (CardioLab, GE Healthcare). Univariate and multivariate logistic regressions (LogR) were used to evaluate association with AF development. RESULTS: A total of 242 consecutive patients (81% male; mean age 66 ± 11 years) were divided into derivation (n =142) and validation (n = 100) cohorts. Forty-two percent developed AF over median follow-up of 330 days. In multivariate LogR (derivation cohort), proximal to distal coronary sinus time (pCS-dCS) ≥70 ms (odds ratio [OR] 16.7; 95% confidence interval [CI] 5.6-49), pCS time ≥36 ms (OR 4.5; 95% CI 1.5-13), and CHADS2-VASc score ≥3 (OR 4.3; 95% CI 1.6-11.8) were independently associated with new AF during follow-up. The Atri-Risk Conduction Index (ARCI) score was created with 0 as minimal and 4 as high-risk using pCS-dCS ≥70 ms = 2 points; pCS ≥36 ms = 1 point; and CHADS2-VASc score ≥3 = 1 point. In the validation cohort, 0% of patients with ARCI score = 0 developed AF, whereas 89% of patients with ARCI score = 4 developed AF. CONCLUSION: We developed and validated a risk score using atrial conduction parameters and clinical risk factors to predict AF after tAFL ablation. It stratifies low-, moderate-, and high-risk patients and may be helpful in individualizing approaches to AF monitoring and anticoagulation.

Characterization of Biomarkers of Thrombo-Inflammation in Patients with First-Diagnosed Atrial Fibrillation.

Patients with first-diagnosed atrial fibrillation (FDAF) exhibit major adverse cardiovascular events (MACEs) during follow-up. Preclinical models have demonstrated that thrombo-inflammation mediates adverse cardiac remodeling and atherothrombotic events. We have hypothesized that thrombin activity (FIIa) links coagulation with inflammation and cardiac fibrosis/dysfunction. Surrogate markers of the thrombo-inflammatory response in plasma have not been characterized in FDAF. In this prospective longitudinal study, patients presenting with FDAF (n = 80), and 20 matched controls, were included. FIIa generation and activity in plasma were increased in the patients with early AF compared to the patients with chronic cardiovascular disease without AF (controls; p < 0.0001). This increase was accompanied by elevated biomarkers (ELISA) of platelet and endothelial activation in plasma. Pro-inflammatory peripheral immune cells (TNF-α+ or IL-6+) that expressed FIIa-activated protease-activated receptor 1 (PAR1) (flow cytometry) circulated more frequently in patients with FDAF compared to the controls (p < 0.0001). FIIa activity correlated with cardiac fibrosis (collagen turnover) and cardiac dysfunction (NT-pro ANP/NT-pro BNP) surrogate markers. FIIa activity in plasma was higher in patients with FDAF who experienced MACE. Signaling via FIIa might be a presumed link between the coagulation system (tissue factor-FXa/FIIa-PAR1 axis), inflammation, and pro-fibrotic pathways (thrombo-inflammation) in FDAF.

Left atrial shape as a marker of atrial myopathy in embolic stroke of undetermined source.

AIMS: Embolic stroke of undetermined source (ESUS) results in significant morbidity. A left atrial (LA) myopathy is implicated in a proportion of these patients. We hypothesized that LA shape varies by cause of stroke [CE (cardioembolic) vs. ESUS]. METHODS AND RESULTS: A total of 236 ischaemic stroke and atrial fibrillation (AF) patients and controls were recruited prospectively. AF was classified as paroxysmal AF (PAF) or persistent AF (PersAF). Stroke patients comprised CE stroke secondary to AF and ESUS. There were 81 AF (47 PAF, 34 PersAF), 50 ESUS, 57 CE patients [subdivided into CE with PAF (CEpaf) and CE with PersAF (CEpers)], and 48 controls. Echocardiographic parameters including LA volume, function, and shape/sphericity (3D LA sphericity and 2D-derived LA circularity, ellipticity, sphericity, and eccentricity indices) were evaluated. Increased LA volume and sphericity with LA dysfunction were present in CE, AF, and ESUS groups compared with controls. K-means cluster analysis demonstrated a spectrum of LA myopathy with controls at the lowest and CEpers and PersAF at the upper extremes, with ESUS, PAF, and CEpaf being similar and falling between these extremes. After adjusting for age, sex, and left ventricular (LV) and LA parameters, LA sphericity markers differentiated ESUS from controls (P < 0.01). CONCLUSION: Alterations in LA shape are present in ESUS, AF, and CE patients, particularly increased spherical remodelling. The novel markers of LA sphericity proposed may identify LA myopathy in ESUS patients and potentially guide management for secondary prevention.

Pathophysiology and clinical relevance of atrial myopathy.

Atrial myopathy is a condition that consists of electrical, structural, contractile, and autonomic remodeling of the atria and is the substrate for development of atrial fibrillation, the most common arrhythmia. Pathophysiologic mechanisms driving atrial myopathy are inflammation, oxidative stress, atrial stretch, and neurohormonal signals, e.g., angiotensin-II and aldosterone. These mechanisms initiate the structural and functional remodeling of the atrial myocardium. Novel therapeutic strategies are being developed that target the pathophysiologic mechanisms of atrial myopathy. In this review, we will discuss the pathophysiology of atrial myopathy, as well as diagnostic and therapeutic strategies.

The Natural History of Atrial Functional Mitral Regurgitation.

BACKGROUND: The natural history of moderate/severe atrial functional mitral regurgitation (AFMR) is unknown. OBJECTIVES: The authors sought to study the incidence of left ventricular (LV) systolic dysfunction (LVSD), progression or regression of ≥mild-moderate AFMR, and impact on mortality. METHODS: Adults with left atrial (LA) volume index ≥40 mL/m2, ≥mild-moderate AFMR, and follow-up echocardiogram were followed for incident LVSD (ejection fraction <50% and ≥10% lower than baseline), progression of mild-moderate/moderate AFMR to severe, and persistent regression of AFMR to no/trivial. Relation of AFMR progression or regression as time-dependent covariates with all-cause mortality was studied. Incidence of LVSD was compared with patients with no/mild AFMR matched on age, sex, comorbidities and ejection fraction. Patients were followed until mitral intervention, myocardial infarction, or last follow-up. RESULTS: A total of 635 patients (median age 75 years, 51% female, 96% mild-moderate/moderate AFMR, 4% severe AFMR) were included. Over a median 2.2 years (Q1-Q3: 1.0-4.3 years), incidence rates per 100 person-years were 3.2 for LVSD (P = 0.52 vs patients with no/mild AFMR), 1.9 for progression of AFMR, and 3.9 for regression. Female sex and larger LA volume index were independently associated with progression, whereas younger age, male sex, absent atrial fibrillation, and higher LA emptying fraction were independently associated with regression. Neither AFMR progression nor regression was independently associated with mortality. Instead, independent risk factors for mortality included older age, concentric LV geometry, and higher estimated LV filling and pulmonary pressures. CONCLUSIONS: In patients with predominantly mild-moderate/moderate AFMR, regression of MR was more common than progression, but neither was associated with mortality. Instead, diastolic function abnormalities were more important. Over a median 2-year follow-up, LVSD risk was not increased.

Biatrial arrhythmogenic substrate in patients with hypertrophic obstructive cardiomyopathy.

BACKGROUND: Atrial fibrillation (AF) in patients with hypertrophic obstructive cardiomyopathy (HOCM) may be caused by a primary atrial myopathy. Whether HOCM-related atrial myopathy affects mainly electrophysiological properties of the left atrium (LA) or also the right atrium (RA) has never been investigated. OBJECTIVE: The purpose of this study was to characterize atrial conduction and explore differences in the prevalence of conduction disorders, potential fractionation, and low-voltage areas (LVAs) between the RA and LA during sinus rhythm (SR) as indicators of potential arrhythmogenic areas. METHODS: Intraoperative epicardial mapping of both atria during SR was performed in 15 HOCM patients (age 50 ± 12 years). Conduction delay (CD) and conductin block (CB), unipolar potential characteristics (voltages, fractionation), and LVA were quantified. RESULTS: Conduction disorders and LVA were found scattered throughout both atria in all patients and did not differ between the RA and LA (CD: 2.9% [1.9%-3.6%] vs 2.6% [2.1%-6.4%], P = .541; CB: 1.7% [0.9%-3.1%] vs 1.5% [0.5%-2.8%], P = .600; LVA: 4.7% [1.6%-7.7%] vs 2.9% [2.1%-7.1%], P = .793). Compared to the RA, unipolar voltages of single potentials (SPs) and fractionated potentials (FPs) were higher in the LA (SP: P75 7.3 mV vs 10.9 mV; FP: P75 2.0 mV vs 3.7 mV). FP contained low-voltage components in only 18% of all LA sites compared to 36% of all RA sites. CONCLUSION: In patients with HOCM, conduction disorders, LVA, and FP are equally present in both atria, supporting the hypothesis of a primary atrial myopathy. Conceptually, the presence of a biatrial substrate and high-voltage FP may contribute to failure of ablative therapy of atrial tachyarrhythmias in this population.

Clinical Characteristics and Rhythm Outcomes in Patients With Atrial Myopathy After Successful Catheter Ablation of Atrial Fibrillation.

BACKGROUND: Although successful atrial fibrillation (AF) ablation can maintain sinus rhythm and reduce the left atrial (LA) dimension, blunted LA reverse remodeling can be observed in patients with atrial myopathy. We explored the potential mechanisms and long-term outcomes in patients with blunted LA reverse remodeling after successful AF catheter ablation. METHODS AND RESULTS: We included 1685 patients who underwent baseline and 1-year follow-up echocardiograms, had a baseline LA dimension ≥40 mm, and did not have a recurrence of AF within a year. The patients were divided into tertile groups according to the delta value of the change in LA dimension on the preprocedure and 1-year postprocedure echocardiography. After propensity score matching for age, sex, AF type, and LA dimension, 1272 patients were finally included in the analyses (424 in each group; the least/blunted, moderate, and the most reverse remodeling group). The patients in the T1 group (blunted LA reverse remodeling) were independently associated with higher left ventricular mass index (odds ratio [OR], 1.014 [95% CI, 1.005-1.022], P=0.001), change in ΔH2FPEF score (heavy, hypertensive, atrial fibrillation, pulmonary hypertension, elder, filling pressure) score (OR, 1.445 [95% CI, 1.121-1.861], P=0.004), ventricular epicardial adipose tissue volume (OR, 1.010 [95% CI, 1.003-1.017], P=0.003), thinner LA wall thickness (OR, 0.461 [95% CI, 0.271-0.785], P=0.004), lower LA voltage (OR, 0.670 [95% CI, 0.499-0.899], P=0.008), and showed higher long-term AF recurrence (log-rank P<0.001) than other groups. CONCLUSIONS: Blunted LA reverse remodeling after AF catheter ablation, which is suggestive of atrial myopathy, was independently associated with a larger ventricular epicardial adipose tissue volume and worsening of H2FPEF score. Blunted LA reverse remodeling after AF catheter ablation was also an independent predictor for higher recurrences of AF post-1-year AF catheter ablation.

Atrial myopathy.

This paper delves into the progressive concept of atrial myopathy, shedding light on its development and its impact on atrial characteristics. It extensively explores the intricate connections between atrial myopathy, atrial fibrillation (AF), and strokes. Researchers have sought additional contributors to AF-related strokes due to the absence of a clear timing correlation between paroxysmal AF episodes and strokes in patients with cardiac implantable electronic devices. Through various animal models and human investigations, a close interrelation among aging, inflammation, oxidative stress, and stretching mechanisms has been identified. These mechanisms contribute to fibrosis, alterations in electrical properties, autonomic remodeling, and a heightened pro-thrombotic state. These interconnected factors establish a detrimental cycle, exacerbating atrial myopathy and elevating the risk of sustained AF and strokes. By emphasizing the significance of atrial myopathy and the risk of strokes that are distinct from AF, the paper also discusses methods for identifying patients with atrial myopathy. Moreover, it proposes an approach to incorporate the concept of atrial myopathy into clinical practice to guide anticoagulation decisions in individuals with AF.

Biatrial myopathy in heart failure with preserved ejection fraction.

AIM: Left atrial (LA) myopathy is increasingly recognized as an important phenotypic trait in heart failure (HF) with preserved ejection fraction (HFpEF). Right atrial (RA) remodelling and dysfunction also develop in HFpEF, but little data are available regarding the clinical characteristics and pathophysiology among patients with isolated LA, RA, or biatrial myopathy. METHODS AND RESULTS: Patients with HFpEF underwent invasive haemodynamic exercise testing, comprehensive imaging including speckle tracking strain echocardiography, and clinical follow-up at Mayo Clinic between 2006 and 2018. LA myopathy was defined as LA volume index >34 ml/m2 and/or LA reservoir strain ≤24% and RA myopathy by RA volume index >39 ml/m2 in men and >33 ml/m2 in women and/or RA reservoir strain ≤19.8%. Of 476 consecutively evaluated patients with HFpEF defined by invasive exercise testing with evaluable atrial structure/function, 125 (26%) had no atrial myopathy, 147 (31%) had isolated LA myopathy, 184 (39%) had biatrial myopathy, and 20 (4%) had isolated RA myopathy. Patients with HFpEF and biatrial myopathy had more atrial fibrillation, poorer left ventricular systolic and diastolic function, more severe pulmonary vascular disease, tricuspid regurgitation, ventricular interdependence and right ventricular dysfunction, and poorer cardiac output reserve with exercise. There were 94 patients with events over a median follow-up of 2.9 (interquartile range 1.4-4.6) years. Individuals with biatrial myopathy had an 84% higher risk of HF hospitalization or death as compared to those with isolated LA myopathy (hazard ratio 1.84; 95% confidence interval 1.16-2.92, p = 0.01). CONCLUSIONS: Biatrial myopathy identifies patients with more advanced HFpEF characterized by more severe pulmonary vascular disease, right HF, poorer cardiac reserve, and a greater risk for adverse outcomes. Further study is required to define optimal strategies to treat and prevent biatrial myopathy in HFpEF.

Heart rate fragmentation and brain MRI markers of small vessel disease in MESA.

INTRODUCTION: Heart rate (HR) fragmentation indices quantify breakdown of HR regulation and are associated with atrial fibrillation and cognitive impairment. Their association with brain magnetic resonance imaging (MRI) markers of small vessel disease is unexplored. METHODS: In 606 stroke-free participants of the Multi-Ethnic Study of Atherosclerosis (mean age 67), HR fragmentation indices including percentage of inflection points (PIP) were derived from sleep study recordings. We examined PIP in relation to white matter hyperintensity (WMH) volume, total white matter fractional anisotropy (FA), and microbleeds from 3-Tesla brain MRI completed 7 years later. RESULTS: In adjusted analyses, higher PIP was associated with greater WMH volume (14% per standard deviation [SD], 95% confidence interval [CI]: 2, 27%, P = 0.02) and lower WM FA (-0.09 SD per SD, 95% CI: -0.16, -0.01, P = 0.03). DISCUSSION: HR fragmentation was associated with small vessel disease. HR fragmentation can be measured automatically from ambulatory electrocardiogram devices and may be useful as a biomarker of vascular brain injury.