Atrial Abnormalities Research Articles

Associations between biomarkers and P-wave indices in patients with heart failure

Abstract Background Atrial structural abnormalities linked to the risk of atrial fibrillation (AF), as indicated by P-wave indices on surface ECG, are associated with the fibrotic transformation of the atrial myocardium. To what extent incident AF can be predicted by ECG characteristics in patients with advanced atrial structural remodeling, such as patients with heart failure (HF), is less well studied. Purpose To evaluate the association between P-wave indices and biomarkers implicated in cardiac fibrosis, and incident AF in patients with HF. Methods Patients with new-onset or worsening of HF were prospectively recruited in a observational study (n=501) and followed-up for 5 years. Blood samples were collected for analysis using proximity extension assay that included a subset of biomarkers that were associated with fibrosis development (TIMP-2, MMP-2, MMP-3, MMP-9, ST-2, GDF-15, Gal-3). All ECGs ever recorded in the hospital catchment area were exported in digital format and processed using Glasgow algorithm for calculation of the P-wave indices (P-wave duration [PWD], P-wave terminal force in V1 [PTFV1] and P-wave axis [Paxis]) and rhythm identification. AF diagnosis was ascertained by manual ECG review. Only patients who did not have AF reported or ECG documented at enrolment were included in the analysis. Of those subjects, 121 patients also had biomarkers of fibrosis analyzed. Cox-regression analyses were used to assess biomarkers’ and p-wave indices’ associations with incident AF. Results After exclusion of patients with prevalent AF (n=317), 184 patients comprised the study group (mean age of 71 years, 33.2% women, 121 patients with biomarker data available). During follow-up, incident AF was observed in 39 patients. At enrolment, PWD>120 ms was observed in 38.7%, abnormal PTFV1>40 mm*ms in 24.5% and Paxis<0° in 5.4%. Among the seven biomarkers assessed, five demonstrated significant associations with incident AF in adjusted analyses: TIMP4 (HR 1.78; 95%CI 1.03-3.05; p=0.037); MMP2 (HR 1.97; 95%CI 1.03-3.80; p=0.042), MMP3 (HR 1.39; 95%CI 1.03-1.88; p=0.031); ST2 (HR 1.91; 95%CI 1.29-2.83; p=0.001) and GDF-15 (HR 2.56; 95%CI 1.50-4.35; p=0.001) (Figure 1). However, none of the tested P-wave variables (P-wave duration, P-wave terminal force, and P-wave axis) were associated to incident AF. Conclusions In this prospective long-term follow-up study of patients admitted for acute HF, biomarkers with proven associations to fibrosis were strongly associated with incident AF. P-wave indices used for prediction of AF in epidemiological cohorts appear to have limited value in patients with HF who have high prevalence of ECG atrial abnormalities at baseline.

The Significance of Right-Sided Precordial ECG Leads (V3R and V4R) in Assessing Right Ventricular Dysfunction: ASingle Center Cross-Sectional Study.

Right ventricular systolic dysfunction is associated with poor prognosis and increased mortality rates. Our objective was to investigate ECG changes in patients with this condition, focusing on the right-sided precordial leads. In this cross-sectional study, 60 patients with right ventricular dysfunction were included from April 2020 to April 2021. Cardiac structure and function were assessed using 2D transthoracic echocardiography. Standard 12-lead electrocardiograms and right-sided precordial ECGs (V3R-V4R) were obtained and analyzed for QRS complex configuration, ST-segment elevation, and T-wave morphology. In our study, the majority were male (70.0%) with a mean age of 58.76 years. The most common initial diagnoses were pulmonary thromboembolism (43.3%), chronic obstructive pulmonary disease (26.7%), and pulmonary hypertension (25.0%). The predominant ECG finding in the right-sided precordial leads (V3R, V4R) was a deep negative T wave (90.0%). Patients with severe right ventricular systolic dysfunction often exhibited a qR pattern (41.2%), whereas those with nonsevere dysfunction showed rS and QS patterns (55.8%). Approximately 41.0% of severe RV dysfunction cases had ST segment depression in the right-sided precordial leads, and 28.0% of patients displayed signs of right atrial abnormality. The study found that qR, rS, and QS patterns were more prevalent in V3R and V4R leads among patients with severe and nonsevere right ventricular systolic dysfunction. The most common ECG feature observed was deep T-wave inversion in these leads. The study recommends using right-sided precordial leads in all patients with RV systolic dysfunction for early detection and risk stratification.

P055 ELECTROCARDIOGRAPHIC ABNORMALITIES AND ASSOCIATED FACTORS IN NORMOTENSIVE TYPE II DIABETIC PATIENTS

Background/Objective: Type II diabetes mellitus (T2DM) is a coronary heart disease (CHD) equivalent in the presence of target organ damage or at least three cardiovascular disease (CVD) risk factors. Resting electrocardiography (ECG) is recommended in T2DM patients only in the presence of hypertension or on suspicion of CVD. ECG abnormalities occur early in T2DM, are associated with future cardiovascular events/mortality after adjustment for traditional CVD risk factors. Early screening and detection may improve long term survival in T2DM patients hence, aim of study- to assess the patterns and factors associated with ECG abnormalities in T2DM patients without co-existing hypertension. Methods: One hundred normotensive (BP<130/80mmHg, not on any antihypertensive agent) T2DM patients were recruited consecutively, from the Endocrinology and Diabetes clinics of the Medical Outpatient Clinic and Family Medicine department of the University of Nigeria Teaching Hospital. Consents were obtained, before interviewers, administered questionnaire to get the biodata, T2DM history, complications and treatment. Anthropometric and blood pressure readings were taken using standard methods. A 12-hour overnight fasting blood sample was taken for biochemical assessment of blood glucose, glycated haemoglobin, lipids, urea and creatinine. A 12 lead ECG was performed and interpreted by one cardiologist using the Minnesota ECG code criteria. Descriptive statistics was used for patterns of ECG abnormalities while association between categorical variables were cross tabulated and tested using chi square. Results: Participants were majorly females 68(68.0%), overweight/obese 52(52.0%) with a mean age of 55.56±9.89 years. Duration of T2DM illness post diagnosis was 6.57±6.26years. T2DM was poorly controlled in 92(92.0%) while 93(93.0%) had dyslipidaemia. ECG was abnormal in 56(56.0%) with multiple abnormality in 12(21.4)%. Left atrial abnormality was the commonest 14(25.0%) ECG abnormality. No factor was associated with ECG abnormality. Conclusions: ECG abnormalities are common in T2DM, occurring early in the absence of co-existing hypertension. ECG should be done at diagnosis of T2DM irrespective of CVD risk factors, with frequent monitoring than recommended by guidelines. Table. Pattern of electrocardiographic abnormalities in normotensive type II diabetic patients.

Structural and functional abnormalities of left-sided cardiac chambers in Barlow's disease without significant mitral regurgitation.

This study aims to explore the presence of left ventricular (LV) and left atrial (LA) morphological and functional abnormalities in patients with Barlow's disease (BD) without significant mitral regurgitation (MR) and to investigate whether these abnormalities may predict MR progression. Consecutive patients with BD were retrospectively identified from two tertiary centres; those with MR graded from trivial to mild-to-moderate were selected and matched with healthy controls in a 1:1 ratio. Conventional and speckle-tracking echocardiographic data were collected. The development of moderate-to-severe or greater MR was evaluated on follow-up echocardiograms. Patients with BD (n = 231) showed increased LV dimensions and indexed LV mass (LVMi) in comparison with controls (P < 0.001); LV remodelling worsened with higher MR severity and was accompanied by an increased prevalence of eccentric LV hypertrophy (eLVH). Moreover, BD patients had larger LA volumes and more impaired LA reservoir strain vs. controls (P < 0.001), while LV strain was similar between the two groups. Multivariable linear regression analyses in the overall population identified BD and MR grade as independent predictors of remodelling markers (LV dimensions, LVMi, and LA volume) and BD as independent correlate of LA strain. MR progression was observed in 51 BD subjects (out of 170 patients with available follow-up). On Cox regression analysis, age, eLVH, mild-to-moderate MR, and mitral annular disjunction (MAD) emerged as independent predictors of MR progression. BD patients without significant MR show early LV and LA remodelling, together with reduced LA strain. MR progression was associated with eccentric LV remodelling, MAD, and MR severity.

Impact of Type 2 Diabetes Mellitus on Left Atrioventricular Coupling and Left Atrial Deformation in Patients with Essential Hypertension: An MRI Feature Tracking Study.

Hypertension (HTN) and type 2 diabetes mellitus (T2DM) are both associated with left ventricular (LV) and left atrial (LA) structural and functional abnormalities; however, the relationship between the left atrium and ventricle in this population is unclear. To identify differences between hypertensive patients with and without T2DM as the basis for further investigation the atrioventricular coupling relationship. Cross-sectional, retrospective study. 89 hypertensive patients without T2DM [HTN (T2DM-)] (age: 58.4 +/- 11.9 years, 48 male), 62 hypertensive patients with T2DM [HTN (T2DM+)] (age: 58.5 +/- 9.1 years, 32 male) and 70 matched controls (age: 55.0 +/- 9.6 years, 37 male). 2D balanced steady-state free precession cine sequence at 3.0 T. LA reservoir, conduit, and booster strain (εs, εe, and εa) and strain rate (SRs, SRe, and SRa), LV radial, circumferential and longitudinal peak strain (PS) and peak systolic strain rate and peak diastolic strain rate (PSSR and PDSR) were derived from LA and LV cine images and compared between groups. Chi-square or Fisher's exact test, one-way analysis of variance, analysis of covariance, Pearson's correlation, multivariable linear regression analysis, and intraclass correlation coefficient. A P value <0.05 was considered significant. Compared with controls, εs, εe, SRe and PS-longitudinal, PDSR-radial, and PDSR-longitudinal were significantly lower in HTN (T2DM-) group, and they were even lower in HTN (T2DM+) group than in both controls and HTN (T2DM-) group. SRs, εa, SRa, as well as PS-radial, PS-circumferential, PSSR-radial, and PSSR-circumferential were significantly lower in HTN (T2DM+) compared with controls. Multivariable regression analyses demonstrated that: T2DM and PS-circumferential and PS-longitudinal (β = -4.026, -0.486, and -0.670, respectively) were significantly associated with εs; T2DM and PDSR-radial and PDSR-circumferential were significantly associated with εe (β = -3.406, -3.352, and -6.290, respectively); T2DM and PDSR-radial were significantly associated with SRe (β = 0.371 and 0.270, respectively); T2DM and PDSR-longitudinal were significantly associated with εa (β = -1.831 and 5.215, respectively); and PDSR-longitudinal was significantly associated with SRa (β = 1.07). In hypertensive patients, there was severer LA dysfunction in those with coexisting T2DM, which may be associated with more severe LV dysfunction and suggests adverse atrioventricular coupling. 3. Stage 3.

Functional substrate mapping of atrium in patients with atrial scar: A novel method to predict critical isthmus of atrial tachycardia.

Atrial tachycardia (AT) is a common rhythm disorder, especially in patients with atrial structural abnormalities. Although voltage mapping can provide a general picture of structural alterations which are mainly secondary to prior ablations, surgery or pressure/volume overload, data is scarce regarding the functional characteristics of low voltage regions in the atrium to predict critical isthmus of ATs. Recently, functional substrate mapping (FSM) emerged as a potential tool to evaluate the functionality of structurally altered regions in the atrium to predict critical sites of reentry. Current evidence suggested a clear association between deceleration zones of isochronal late activation mapping (ILAM) during sinus/paced rhythm and critical isthmus of reentry in patients with left AT. Therefore, these areas seem to be potential ablation targets even not detected during AT. Furthermore, abnormal conduction detected by ILAM may also have a role to identify the potential substrate and predict atrial fibrillation outcome after pulmonary vein isolation. Despite these promising findings, the utility of such an approach needs to be evaluated in large-scale comparative studies. In this review, we aimed to share our experience and review the current literature regarding the use of FSM during sinus/paced rhythm in the prediction of re-entrant ATs and discuss future implications and potential use in patients with atrial low-voltage areas.

Atrial Septal Abnormalities and Cryptogenic Stroke: A Cross-Sectional Study.

Cryptogenic stroke, whose underlying pathology is unknown, accounts for 30-40% of all ischemic strokes. Studies have mentioned the association between atrial septal abnormalities and cryptogenic stroke, but there are still disparities in the results among different studies. We aimed to clarify the prevalence of atrial septal abnormalities in patients with cryptogenic stroke. We conducted a cross-sectional study on 91 patients with cryptogenic stroke/transient ischemic attack from March 2021 to March 2022. We evaluated the demographic data of the patients and also the existence of neurologic attacks. Furthermore, echocardiography was performed to determine the type of atrial septal abnormality. Out of 91 patients with cryptogenic stroke/transient ischemic attack, 16 patients (17.5%) had patent foramen ovale, 1 man (1.1%) had atrial septal aneurysm, and 1 woman (1.1%) had an atrial septal defect. Patients with patent foramen ovale were significantly younger than those without. The size of patent foramen ovale in patients with cryptogenic stroke was larger than those with transient ischemic attack, but this difference was not significant. Also, the size of the patent foramen ovale (length and width) was not significantly related to any of the demographic variables (p-value = 0.544, 0.604). Based on our results, the prevalence of atrial septal abnormalities was relatively high. Considering these issues and the importance of preventing neurological accidents in patients, especially young people, it is recommended to always consider atrial septal disorders and, if diagnosed, to carry out the necessary treatment in this field.

2024 Guidelines of the Taiwan Society of Cardiology for the Diagnosis and Treatment of Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a multi-organ systemic syndrome that involves cardiac and extra-cardiac pathophysiological abnormalities. Its growing prevalence causes a major public concern worldwide. HFpEF is usually associated with multiple comorbidities, and non-cardiovascular death is common in patients with HFpEF. In Asia, patients with HFpEF has a younger age, higher prevalence of diabetes and chronic kidney disease than Western countries. A 2-step diagnostic algorithm is recommended in this guideline. In the first step, the diagnosis of HFpEF can be made if patients have symptoms and/or signs of heart failure, left ventricular ejection fraction ≥ 50%, increased natriuretic peptide, and objective evidence of left atrial or left ventricular abnormalities or raised left ventricular filling pressure. If diagnosis is still uncertain, invasive or noninvasive stress test can be performed in the second step. Comorbidities need to be controlled in HFpEF. Weight reduction for obesity and supervised exercise training are recommended for HFpEF. For pharmacological therapy, diuretic is used to relieve congestion and sodium-glucose cotransporter 2 inhibitor, empagliflozin or dapagliflozin, is recommended to improve prognosis of HFpEF. The research on HFpEF is advancing at a rapid pace. It is expected that newer modalities for diagnosis and management of HFpEF could appear in the near future.

Reduced plakoglobin increases the risk of sodium current defects and atrial conduction abnormalities in response to androgenic anabolic steroid abuse.

Androgenic anabolic steroids (AAS) are commonly abused by young men. Male sex and increased AAS levels are associated with earlier and more severe manifestation of common cardiac conditions, such as atrial fibrillation, and rare ones, such as arrhythmogenic right ventricular cardiomyopathy (ARVC). Clinical observations suggest a potential atrial involvement in ARVC. Arrhythmogenic right ventricular cardiomyopathy is caused by desmosomal gene defects, including reduced plakoglobin expression. Here, we analysed clinical records from 146 ARVC patients to identify that ARVC is more common in males than females. Patients with ARVC also had an increased incidence of atrial arrhythmias and Pwave changes. To study desmosomal vulnerability and the effects of AAS on the atria, young adult male mice, heterozygously deficient for plakoglobin (Plako+/-), and wild type (WT) littermates were chronically exposed to 5α-dihydrotestosterone (DHT) or placebo. The DHT increased atrial expression of pro-hypertrophic, fibrotic and inflammatory transcripts. In mice with reduced plakoglobin, DHT exaggerated Pwave abnormalities, atrial conduction slowing, sodium current depletion, action potential amplitude reduction and the fall in action potential depolarization rate. Super-resolution microscopy revealed a decrease in NaV1.5membrane clustering in Plako+/- atrial cardiomyocytes after DHT exposure. In summary, AAS combined with plakoglobin deficiency cause pathological atrial electrical remodelling in young male hearts. Male sex is likely to increase the risk of atrial arrhythmia, particularly in those with desmosomal gene variants. This risk is likely to be exaggerated further by AAS use. KEY POINTS: Androgenic male sex hormones, such as testosterone,might increase the risk of atrial fibrillation in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), which is often caused by desmosomal gene defects (e.g. reduced plakoglobin expression). In this study, we observed a significantly higher proportion of males who had ARVC compared with females, and atrial arrhythmias and Pwave changes represented a common observation in advanced ARVC stages. In mice with reduced plakoglobin expression, chronic administration of 5α-dihydrotestosterone led to Pwave abnormalities, atrial conduction slowing, sodium current depletion and a decrease in membrane-localized NaV1.5 clusters. 5α-Dihydrotestosterone, therefore, represents a stimulus aggravating the pro-arrhythmic phenotype in carriers of desmosomal mutations and can affect atrial electrical function.

A Genomic Link From Heart Failure to Atrial Fibrillation Risk: FOG2 Modulates a TBX5/GATA4-Dependent Atrial Gene Regulatory Network.

The relationship between heart failure (HF) and atrial fibrillation (AF) is clear, with up to half of patients with HF progressing to AF. The pathophysiological basis of AF in the context of HF is presumed to result from atrial remodeling. Upregulation of the transcription factor FOG2 (friend of GATA2; encoded by ZFPM2) is observed in human ventricles during HF and causes HF in mice. FOG2 expression was assessed in human atria. The effect of adult-specific FOG2 overexpression in the mouse heart was evaluated by whole animal electrophysiology, in vivo organ electrophysiology, cellular electrophysiology, calcium flux, mouse genetic interactions, gene expression, and genomic function, including a novel approach for defining functional transcription factor interactions based on overlapping effects on enhancer noncoding transcription. FOG2 is significantly upregulated in the human atria during HF. Adult cardiomyocyte-specific FOG2 overexpression in mice caused primary spontaneous AF before the development of HF or atrial remodeling. FOG2 overexpression generated arrhythmia substrate and trigger in cardiomyocytes, including calcium cycling defects. We found that FOG2 repressed atrial gene expression promoted by TBX5. FOG2 bound a subset of GATA4 and TBX5 co-bound genomic locations, defining a shared atrial gene regulatory network. FOG2 repressed TBX5-dependent transcription from a subset of co-bound enhancers, including a conserved enhancer at the Atp2a2 locus. Atrial rhythm abnormalities in mice caused by Tbx5 haploinsufficiency were rescued by Zfpm2 haploinsufficiency. Transcriptional changes in the atria observed in human HF directly antagonize the atrial rhythm gene regulatory network, providing a genomic link between HF and AF risk independent of atrial remodeling.

Developing Pharmacological Therapies for Atrial Fibrillation Targeting Mitochondrial Dysfunction and Oxidative Stress: A Scoping Review.

Atrial fibrillation (AF) is a cardiac arrhythmia caused by electrophysiological anomalies in the atrial tissue, tissue degradation, structural abnormalities, and comorbidities. A direct relationship exists between AF and altered mitochondrial activity resulting from membrane potential loss, contractile dysfunction, or decreased ATP levels. This review aimed to elucidate the role of mitochondrial oxidative mechanisms in AF pathophysiology, the impact of mitochondrial oxidative stress on AF initiation and perpetuation, and current therapies. This review followed the Preferred Reporting Items for Systematic Reviews and the Meta-Analysis Extension for Scoping Reviews. PubMed, Excerpta Medica Database, and Scopus were explored until June 2023 using "MESH terms". Bibliographic references to relevant papers were also included. Oxidative stress is an imbalance that causes cellular damage from excessive oxidation, resulting in conditions such as AF. An imbalance in reactive oxygen species production and elimination can cause mitochondrial damage, cellular apoptosis, and cardiovascular diseases. Oxidative stress and inflammation are intrinsically linked, and inflammatory pathways are highly correlated with the occurrence of AF. AF is an intricate cardiac condition that requires innovative therapeutic approaches. The involvement of mitochondrial oxidative stress in the pathophysiology of AF introduces novel strategies for clinical treatment.

Myocardial Mechanics and Associated Valvular and Vascular Abnormalities in Left Ventricular Noncompaction Cardiomyopathy.

Left ventricular (LV) non-compaction (LVNC) is a rare genetic cardiomyopathy due to abnormal intra-uterine arrest of compaction of the myocardial fibers during endomyocardial embryogenesis. Due to the partial or complete absence of LV compaction, the structure of the LV wall shows characteristic abnormalities, including a thin compacted epicardium and a thick non-compacted endocardium with prominent trabeculations and deep intertrabecular recesses. LVNC is frequently associated with chronic heart failure, life-threatening ventricular arrhythmias, and systemic embolic events. According to recent findings, in the presence of LVNC, dysfunctional LV proved to be associated with left atrial volumetric and functional abnormalities and consequential dilated and functionally impaired mitral annulus, partly explaining the higher prevalence of regurgitation. Although the non-compaction process morphologically affects only the LV, signs of remodeling of the right heart were also detected. Moreover, dilation and stiffening of the aorta were present. The aim of the present detailed review was to summarize findings regarding changes in cardiac mechanics, valvular abnormalities, and vascular remodeling detected in patients with LVNC.

P-wave characteristics as electrocardiographic markers of atrial abnormality in prediction of incident atrial fibrillation – The Malmö Preventive Project

BackgroundP-wave indices reflect atrial abnormalities contributing to atrial fibrillation (AF). We aimed to assess a comprehensive set of P-wave characteristics for prediction of incident AF in a population-based setting. MethodsMalmö Preventative Project (MPP) participants were reexamined in 2002–2006 with electrocardiographic (ECG) and echocardiographic examinations and followed for 5 years. AF-free subjects (n = 983, age 70 ± 5 years, 38% females) with sinus rhythm ECGs were included in the study. ECGs were digitally processed using the Glasgow algorithm. P-wave duration, axis, dispersion, P-terminal force in lead V1 and interatrial block (IAB) were evaluated. ECG risk score combining the morphology, voltage and length of P-wave (MVP score) was calculated. New-onset diagnoses of AF were obtained from nation-wide registers. ResultsDuring follow up, 66 patients (7%) developed AF. After adjustment for age and gender, the independent predictors of AF were abnormal P-wave axis > 75° (HR 1.63 CI95% 1.95–11.03) and MVP score 4 (HR 6.17 CI 95% 1.76–21.64), both correlated with LA area: Person r − 0.146, p < 0.001 and 0.192, p < 0.001 respectively. Advanced IAB (aIAB) with biphasic P-wave morphology in leads III and aVF was the most prevalent variant of aIAB and predicted AF in a univariate model (HR 2.59 CI 95% 1.02–6.58). ConclusionP-wave frontal axis and MVP score are ECG-based AF predictors in the population-based cohort. Our study provides estimates for prevalence and prognostic importance of different variants of aIAB, providing a support to use biphasic P-wave morphology in lead aVF as the basis for aIAB definition.

Interaction effect of type 2 diabetes mellitus and hypertension on left atrial function: a three-dimensional echocardiography study.

Type 2 diabetes mellitus (T2DM) and hypertension (HT) often coexist and contribute to left atrial (LA) functional abnormalities. The aim of the present study was to explore whether there is a potential interaction effect between T2DM and HT on LA function. A total of 135 patients (45 with T2DM only, 45 with HT only, and 45 with both T2DM and HT) were enrolled and compared to 45 age- and sex-matched controls. LA volume fraction, including LA ejection fraction (LAEF), LA expansion index (LAEI), LA passive emptying fraction (LAPEF), and LA active emptying fraction (LAAEF), and strain parameters, including LA reservoir longitudinal strain (LASr), LA conduit longitudinal strain (LAScd), and LA contraction longitudinal strain (LASct), were obtained using three-dimensional echocardiography (3DE). Patients with T2DM had significantly more impaired LA reservoir and conduit functions compared to those without T2DM (P<0.05), and patients with HT had a significantly more impaired LA reservoir function, conduit function, and booster pump function compared to those without HT (P<0.05). Two-way analysis of variance showed that there were significant additive interaction effects between T2DM and HT with respect to LASr (PT2DM + HT =0.002) and LAScd (PT2DM + HT =0.001). Generalized linear model demonstrated that T2DM + HT had a greater relative contribution than either T2DM or HT alone to the LA strain indexes, even after adjustment for other confounders (LASr, βT2DM + HT =-3.931, 95% CI: -6.237 to -1.624, P=0.001; LAScd, βT2DM + HT=-3.781, 95% CI: -5.653 to -1.908, P<0.001). Both T2DM and HT had an adverse effect on LA function. The coexistence of both conditions further impaired LA performance in an additive interaction fashion.

Genetic Atrial Cardiomyopathies: Common Features, Specific Differences, and Broader Relevance to Understanding Atrial Cardiomyopathy.

Atrial cardiomyopathy is a condition that causes electrical and contractile dysfunction of the atria, often along with structural and functional changes. Atrial cardiomyopathy most commonly occurs in conjunction with ventricular dysfunction, in which case it is difficult to discern the atrial features that are secondary to ventricular dysfunction from those that arise as a result of primary atrial abnormalities. Isolated atrial cardiomyopathy (atrial-selective cardiomyopathy [ASCM], with minimal or no ventricular function disturbance) is relatively uncommon and has most frequently been reported in association with deleterious rare genetic variants. The genes involved can affect proteins responsible for various biological functions, not necessarily limited to the heart but also involving extracardiac tissues. Atrial enlargement and atrial fibrillation are common complications of ASCM and are often the predominant clinical features. Despite progress in identifying disease-causing rare variants, an overarching understanding and approach to the molecular pathogenesis, phenotypic spectrum, and treatment of genetic ASCM is still lacking. In this review, we aim to analyze the literature relevant to genetic ASCM to understand the key features of this rather rare condition, as well as to identify distinct characteristics of ASCM and its arrhythmic complications that are related to specific genotypes. We outline the insights that have been gained using basic research models of genetic ASCM in vitro and in vivo and correlate these with patient outcomes. Finally, we provide suggestions for the future investigation of patients with genetic ASCM and improvements to basic scientific models and systems. Overall, a better understanding of the genetic underpinnings of ASCM will not only provide a better understanding of this condition but also promises to clarify our appreciation of the more commonly occurring forms of atrial cardiomyopathy associated with ventricular dysfunction.

Electrocardiographic left atrial abnormality and risk of heart failure

IntroductionThe association and the racial differences of the electrocardiographic markers of left atrial abnormality (ECG-LAA) with heart failure (HF) are unclear. MethodsWe examined the cross-sectional association of ECG-LAA, defined as deep terminal negativity of P wave in V1 (DTNPV1) with HF in 8460 participants (51.5% women, 60.3 ± 13.5 age and 49.8% Whites) from the US Third National Health and Nutrition Examination Survey. We excluded participants without P-wave in their ECG or with ECG findings that interfere with measurements of P-wave. DTNPV1 was automatically measured from ECGs processed at a central lab. Values of DTNPV1 ≥ 100 μV were considered abnormal. Past medical history of HF was identified through health interviews. Multivariable logistic regression analysis was used to examine the associations of DTNPV1 with HF. ResultsAbnormal DTNPV1 was detected in 3.2% (n = 271) of the participants. HF was significantly more common in individuals with abnormal, compared to those with normal, DTNPV1 (14.7% vs. 4.8%, respectively; p-value <0.001). In a model adjusted for socio-demographics and cardiovascular risk factors, ECG-LAA was associated with 98% increased odds of HF (OR (95% CI): 1.98 (1.30–3.01), p < 0.001). This association was stronger in non-White (vs. White) participants (OR (95% CI): 3.14 (1.82–5.43) vs. 1.01 (0.51–1.97), respectively; interaction p-value =0.01), but consistent in subgroups stratified by age and sex. ConclusionsECG-LAA, defined as abnormal DTNPV1, is associated with an increased risk of HF, underscoring the role of atrial disease in developing HF. Racial differences in this association exist, possibly suggesting considering ECG-LAA in personalized assessments of HF risk.

Structural and functional abnormalities of cardiac chambers in Barlow disease without significant mitral regurgitation

Abstract Background Limited and conflicting data have been reported on the existence of an early chamber remodelling in patients with Barlow disease (BD) without significant mitral regurgitation (MR). Purpose To explore the presence of left ventricular (LV) and left atrial (LA) morphological and functional abnormalities, evaluated by conventional and speckle-tracking echocardiography, in patients with BD and without significant MR; in addition, potential determinants of MR progression in these patients have been investigated. Methods We retrospectively identified consecutive patients with BD evaluated in two tertiary centers between 2010 and 2021. Only patients with MR graded from trivial to mild-to-moderate, as defined by an integrated multiparametric echocardiographic assessment, were selected. BD patients were matched with healthy controls with similar demographic characteristics and prevalence of cardiovascular risk factors, in a 1:1 ratio. A comprehensive echocardiographic evaluation, including LV and LA strain assessment by speckle-tracking analysis, was performed in all patients. Follow-up echocardiograms, when available, were reviewed in BD patients to evaluate the MR progression. Results A total of 231 patients with BD were included, of which 109 (56%) had trivial or mild MR and the remaining 122 (44%) had mild-to-moderate MR. As showed in Figure 1, patients with BD showed increased LV dimensions and indexed LV mass (LVMi), as compared with controls (all p&amp;lt;0.001); LV remodelling worsened with higher degree of MR (trivial-mild vs mild-to-moderate) and was accompanied by an increased prevalence of eccentric LV hypertrophy (eLVH). Conversely, parameters of LV systolic performance, including LV strain, were similar to controls and between the two groups. In addition, BD patients had larger LA volumes and more impaired LA reservoir strain than controls (p&amp;lt;0.001), without differences in the latter according to MR severity. Multivariable linear regression analyses in the overall population identified BD and MR grade as independent predictors of remodelling markers (LV dimensions, LVMi and LA volumes), and BD as independent correlate of LA reservoir strain. Progression to moderate-to-severe or greater MR was observed in 51 subjects (on 172 with available follow-up) after a median time of 38 (range: 24-68) months. On multivariable Cox regression analysis, LVMi (or alternatively eLVH), together with age, MR grade and the presence of mitral annular disjunction emerged as independent predictors of MR progression (Figure 2). Conclusions Patients with BD and no significant MR show an early LV and LA remodeling, together with a mild impairment of LA reservoir strain, but not of LV function. LV remodelling, and the presence of eLVH in particular, portends a higher risk of MR progression.Comparative echocardiographic analysisMultivariable Cox regression analyses

Abstract 14789: Atrial Anatomical Variations Between Atrial Fibrillation Patients Compared to Other Subjects Without Atrial Fibrillation

Introduction: In this study, we evaluated the anatomical atrial variations using gated cardiac computed tomography (CCT) between patients with and without atrial fibrillation (AF). Hypothesis: The aim of the study is to evaluate if there are specific anatomical characteristics that are associated with poor clinical outcomes following ablation in patients with AF. Methods: We retrospectively included 502 CCT scans of patients with AF prior to their pulmonary vein isolation procedure, and 1058 CCT scans of patients without AF performed to evaluate pulmonary vein anatomy and to rule out coronary artery disease between 2014 to 2017. Anatomical variations of the atria and interatrial septum included the Bachman bundle shunt (BBS - defined as a vascular channel crossing between the atria through the Bachman bundle), and atrial diverticulae. Results: Five-hundred and two patients with AF were older (67±14 vs. 63±13 years, P = 0.039), had a higher prevalence of diabetes mellitus (24.4% vs 14.7%, p = 0.006), and cerebrovascular disease (3.8% vs. 0.9%, p = 0.044) compared to patients without AF. Furthermore, CCTs analysis of AF patients demonstrated a significantly higher prevalence of BBS: (11% vs 4.1%, p &lt;0.0001, left atrial diverticula (19% vs 7.7%), p &lt;0.0001, and right atrial diverticula (9.8% vs 2.1%), P &lt;0.0001 compared to patients without AF. Conclusions: This study is the first to analyze BBS and atrial diverticular prevalence in patients using CCT. We found that patients with AF are associated with a higher prevalence of structural atrial abnormalities including BBS, left and right atrial diverticula in comparison to individuals with no previous history of AF. Whether these anatomical variations influence AF incidence or AF recurrence after catheter ablation is yet to be determined.

Evaluation of the effects of insulin resistance on ECG parameters in obese children.

Obese people are at increased risk of arrhythmia and sudden death, even in the absence of heart dysfunction. Increased insulin resistance, neurohumoral and autonomic changes in obesity can cause atrial and ventricular repolarization abnormalities. This study aimed to investigate the effect on ventricular repolarization parameters and to show the increased risk of ventricular arrhythmia in obese children. The data of 50 obese children aged 2-18 who applied to the Pediatric Endocrinology Outpatient Clinic were evaluated prospectively. In 12-lead ECGs, heart rate, Pmax, Pmin, P-wave dispersion (Pwdisp), QTmax, QTmin, QT dispersion (QTd), QTcmax, QTcmin, QTc interval dispersion (QTcd), Tpeak-Tend interval (Tp-e), Tp-e/QT, Tp-e/QTc were calculated electronically. Tp-e time (0.041 ± 0.004/0.049 ± 0.015/p=0.018) and Tp parameters were measured in obese children with and without insulin resistance. Tp-e/QT ratio was also found to be high (p=0.035). There is a negative correlation between BMI SDS values and QTcmax and QTcmin values in patients with insulin resistance (p=0.015). In our study, the Tp-e interval and Tp-e/QT ratios, which had been revealed in literature to be more sensitive in demonstrating ventricular arrhythmias, were found to be higher in obese individuals with insulin resistance than in those without insulin resistance. Obese individuals with or without insulin resistance should be carefully evaluated in terms of atrial and ventricular depolarization and repolarization parameters with 12-lead ECG during their outpatient controls, and annual 24-hour Holter control should be performed to detect arrhythmias.

Selective blockade of interleukin 6 trans-signaling depresses atrial fibrillation

Atrial fibrillation (AF) has been accepted as an inflammatory atrial myopathy. Interleukin 6 (IL-6)-dependent inflammatory signaling pathways take context-dependent effects on cardiovascular diseases. IL-6 trans-signaling is predominantly pro-inflammatory. However, its effect on AF is unclear. The purpose of this study was to investigate the role of IL-6 trans-signaling in AF. Circulating levels of IL-6, soluble IL-6 receptor, and soluble glycoprotein 130 (sgp130) in patients with AF and controls were measured to estimate the activation of IL-6 trans-signaling. A mouse model of AF was established by transverse aortic constriction surgery. Sgp130Fc administration was used for the selective blockade of IL-6 trans-signaling. Studies were conducted to evaluate the effects and underlying mechanisms of sgp130Fc on AF inducibility and atrial conduction abnormalities and structural remodeling. In patients, the elevation of IL-6 trans-signaling level was positively associated with AF occurrence. IL-6 trans-signaling activation was recapitulated in the mouse model of AF. In transverse aortic constriction-challenged mice, the selective blockade of IL-6 trans-signaling with sgp130Fc attenuated AF inducibility, which was attributable to the amelioration of slow conduction and conduction heterogeneity induced by atrial dilation, fibrosis, and reduction in connexin 40 and redistribution of connexin 43. Sgp130Fc administration also reduced immune cell infiltration and oxidative stress in the mouse atrium and abrogated IL-6 trans-signaling activation-mediated connexin dysregulation and reactive oxygen species production in atrial myocytes. IL-6 trans-signaling activation contributes to AF development, and its selective blockade may promise a novel therapeutic strategy.