Terminal Force Research Articles

Association of abnormal P-wave parameters with all-cause mortality in diffuse large B-cell lymphoma

Patients diagnosed with diffuse large B-cell lymphoma (DLBCL) are at increased risk of developing atrial fibrillation (AF). Abnormal P-wave parameters (PWPs) have been identified as independent predictors of AF, however, their prognostic significance in DLBCL patients remains unknown. Newly diagnosed DLBCL patients from January 2015 to August 2022 were retrospectively included in this study. Patients were devided as with abnormal PWPs or without it. Primary outcome was the all-cause mortality. The median duration of follow-up was 16.3 months. The Kaplan‒Meier method and multivariable COX proportional hazards regression models were used to analyze the relationship between PWPs and all-cause mortality. Logistic regression analyses were performed to identify risk factors associated with PWPs. A total of 374 newly diagnosed DLBCL patients were included, of whom 137 patients exhibited abnormalities in PWPs. Compared to the group with normal PWPs, patients with PWPs abnormalities had a higher proportion of males (p = 0.001), elevated levels of blood urea nitrogen (p = 0.038) and blood creatinine (p = 0.005), and a higher rate of all-cause mortality (p = 0.001). PWPs, particularly P-wave duration (p = 0.017) and P-wave terminal force in lead V1 (PTFV1) (p = 0.001), were independently correlated with all-cause mortality in DLBCL patients. Furthermore, male patients exhibited a higher susceptibility to abnormal PWPs (p = 0.001). PWPs, particularly P-wave duration and PTFV1, serve as simple yet effective prognostic indicators for all-cause mortality in DLBCL patients. Consequently, vigilant monitoring of PWPs, particularly in male patients, is warranted to accurately evaluate the prognosis of DLBCL.

Sex hormones and reproductive factors with cardiac arrhythmia and ECG indices: a mendelian randomization study

BackgroundSex is a determinant of the incidence and etiology of arrhythmia. Observational and basic studies suggest that sex hormones are essential in this process; however, the relationship between sex hormones and arrhythmia remains unclear. Mendelian randomization (MR) was used to investigate the causal relationships between sex hormone levels, arrhythmia, and electrocardiographic (ECG) indices.MethodsLarge genome-wide association studies (GWAS) data on sex hormones, stratified by sex, from the UK biobank consortium, were used as exposure data, and data on atrial fibrillation (AF), atrioventricular block, sick sinus syndrome, paroxysmal tachycardia, and ECG indices were obtained from the FinnGen consortium and summarized large GWAS data. Inverse variance weighting or wald odds was used as the primary analytical method, and weighted medians and MR-Egger regression were used for complementary analyses. The results of the MR of sex hormones and AF from different sources were analyzed using a meta-analysis. Summary-data-based MR analysis was utilized to explore the relationship between sex-hormone related drugs and arrhythmia.ResultsIn men, genetically predicted higher estradiol concentrations were associated with a lower risk of AF (odds ratio: 0.908 [0.852–0.967]; p = 0.0029], whereas genetically predicted higher concentrations of total testosterone were associated with lower heart rate variability. Sex hormones showed no association with atrioventricular block, sick sinus syndrome, paroxysmal tachycardia, resting heart rate, P wave duration, P wave terminal force in lead V1 [PTFV1], PR interval, QRS duration, QTc [QT interval corrected by heart rate], ST duration, spatial [spQRSTa] and frontal [fQRSTa] QRS-T angles in males. In females, there was no significant evidence that sex hormones are associated with arrhythmias or ECG indices.ConclusionIn this study, we identified a potential causal relationship between estradiol and the risk of AF in males. However, there was no significant association between sex hormones and either arrhythmias or ECG indices in females. These results suggested that sex hormones may play a limited role in cardiac arrhythmias, which requires further verification.

Abstract 4145890: P-Wave Parameters on 12-Lead Electrocardiogram after Catheter Ablation: A Comparison between Pulsed Field Ablation and Cryoablation

Background: Catheter ablation (CA) is a well-established treatment for atrial fibrillation (AF). The most popular current methods of CA include radiofrequency ablation (RFA) and cryoablation (CRYO) which are thermal methods of ablation known to affect the autonomic nervous system through ablation of cardiac ganglionated plexi (GP). Pulsed[SC1] -field ablation (PFA) is a newer method of CA with demonstrated efficacy that preferentially affects cardiac cells and spares surrounding structures such as GP through irreversible electroporation which does not lead to chronic fibrosis like RFA or CRYO. Elevations in the marker the marker P terminal force (PTF) have been associated with AF/stroke and have been known to correlate with atrial fibrosis, and higher PTF after cryoablation for patients with paroxysmal AF has been associated with an increased risk of recurrence. The differences in P-wave parameters pre and post PFA have not been studied. Objective: To investigate the differences in P-wave parameters after PFA and compare them to CRYO. Methods: We identified 40 patients who underwent PFA (20 patients) or CRYO (20 patients) for paroxysmal AF and compared P-wave parameters including duration and amplitude in leads aVF, V1 and the PTF calculated as the duration x amplitude of the terminal negative component of the P-wave in V1. Data were obtained from 12-lead electrocardiograms obtained pre and post ablation. Results: The mean age of patients in our study was 61 with 75% male and 33% on antiarrythmics. We noticed a significant reduction in PTF for patients who underwent CRYO (54 mVmS at baseline compared to 36.8 mVmS after CRYO, p = 0.04) and no significant reduction in PTF for patients who underwent PFA (46 mVmS at baseline compared to 38 mVmS after PFA, p = 0.27). There was also a significant increase in HR after CRYO (65 bpm at baseline compared to 78 bpm after CRYO, p=0.01) and no significant change in HR after PFA (61 bpm at baseline compared with 60 bpm after PFA, p=0.8). There was no statistical difference in both groups looking at aVF or total V1 duration or amplitude pre and post ablation. Conclusions: CRYO leads to a significant change in PTF after ablation while PFA does not, consistent with the notion that PFA does not lead to fibrosis and PTF is not a useful marker for measuring risk of recurrence of AF post PFA.

Predicting atrial fibrillation from ECG characteristics

Abstract Background/Introduction Atrial fibrillation (AF) is the most common cardiac arrythmia, and demographic shifts in age continues to increase the prevalence of atrial fibrillation on a global scale. With manifestations of short and intermittent duration, identifying and diagnosing AF often proves to be a challenge. As a consequence, patients who develop AF are at risk of experiencing stroke and other cardiac diseases such as heart failure (HF) before appropriate treatment is initialized. Despite the potential benefits of early AF detection, risk profiling based on electrocardiographic (ECG) findings is currently lacking. Several smaller studies have identified ECG characteristics associated with increased risk of AF, but these characteristics have not been individually evaluated in large-scale nationwide cohorts, and no evidence exists on the additive effect of these ECG characteristics. Purpose We aimed to evaluate the risk of new-onset AF, HF, and stroke according to five ECG characteristics previously linked to AF, in order to identify potential predictors of AF. Methods We used national registers and the Danish Nationwide ECG Cohort to include patients with ECG measurements taken between 2010 and 2022. Patients were grouped according to how many of the following ECG characteristics were present in their baseline ECG: Elevated heart rate (>80), prolonged PR-interval (≥196 ms for women and ≥204 ms for men), biphasic P-waves (positive and negative amplitude within same p-wave), abnormal P terminal force (≥ 6000 mV×ms), and prolonged P-wave duration(≥120 ms). Patients were followed for 2 years to evaluate the risk of atrial fibrillation, heart failure (HF), and stroke, according to baseline ECG characteristics. Results We included 1,505,474 patients of whom 594,702 had exactly one ECG characteristic, 197,367 had two characteristics, 44,983 had three characteristics, 6,390 had four characteristics, and 451 had all five characteristics on their baseline ECG. The risk of developing AF or HF increased with the number of ECG characteristics present on the baseline ECG. Patients with two ECG characteristics had a 2-fold increased risk of AF or HF compared to patients with no ECG characteristics (HR: 2.11 95%CI: 2.05-2.16). Patients with two or more ECG characteristics present on their baseline ECG exceeded a 5% 2-year absolute risk of developing either AF or HF. Among patients with only one ECG characteristic on their baseline ECG, elevated heart rate and prolonged PR interval were the factors most associated with an increased risk of AF compared to patients with none of the ECG characteristics on their baseline ECG. Conclusions The absolute and relative risk of atrial fibrillation, heart failure, and stroke increased with the number of ECG characteristics present on the baseline ECG. We suggest that the ECG characteristics evaluated in this study could be used in screening scenarios for atrial fibrillation to identify high risk patients.Absolute and relative 2-year risksRisk acc. to specific ECG characteristic

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.

Identification of genetic variants associated with exercise-induced atrial fibrillation in high-performing racehorses

Abstract Background Atrial fibrillation (AF) is the most common cardiac arrhythmia in athletes. Despite a lower burden of classical cardiovascular risk factors, the prevalence of AF in athletes is comparable to that in the general population of similar age (~13%, mean age 65.5), suggesting that exercise-induced AF may have different underlying mechanisms. The prevalence of AF in thoroughbred (TB) and standardbred (STB) racehorses is also relatively high (~5%), suggesting exercise as an independent risk factor. Due to selective breeding and complete control of pedigrees, racehorses are well-suited for genetic studies. Common and rare genetic variation explain a substantial part of AF variance, but no study has identified genetic variants associated with exercise-induced AF in any species. Objective In this project, we aimed to use the racehorse as a model to identify genetic variants associated with exercise-induced AF, and in a future study, possibly replicate the results in human athletes. Here we present preliminary results from the genome-wide association study (GWAS) of AF in racehorses. Methods We collected blood or hair samples from 181 STB and TB racehorses in which 71 had paroxysmal or persistent AF verified by ECG. We extracted DNA and performed whole-genome genotyping using a commercial equine genotyping platform (670k markers). We phased and imputed un-genotyped markers and increased the sample size of the control group, using publicly available equine data from similar breeds from the European Nucleotide Archive. We conducted a GWAS of 7.85 million markers in 71 cases and 296 controls using PLINK2 with covariates adjusted for population stratification, batch and sex. Results We identified one significant locus downstream of the protocadherin gene PCDH18 associated with AF in racehorses. The same locus has been associated with the ECG-trait P-wave terminal force in humans. Changes in P-wave terminal force is associated with increased atrial size, delayed interatrial conduction, left ventricular fibrosis and left atrial function, and considered a good predictor of AF occurrence. Several non-significant but interesting signals were also identified including the genes SLC6A15 (amino acid transport), MYBPH (myosin binding), MYF6 and MYOG (myoblast differentiation). Conclusion In these preliminary results, we have identified a new genetic locus associated with AF in racehorses. In addition, we have identified several candidate genes for further studies to elucidate the genetic background of exercise-induced AF. We aim to replicate our findings in a population of human athletes. Our results may aid the development of risk prediction tools for exercise-induced AF and new drugs for tailored treatment of AF in general.

A novel electrocardiogram-based model for prediction of dementia: the Atherosclerosis Risk in Communities (ARIC) study

Abstract Background Current dementia prediction models, such as the UK Biobank Dementia Risk Score (UKBDRS, 12 variables), are limited by having variables that are difficult to obtain, subjectively measured, and self-reported. Although individual ECG parameters are linked to higher dementia risk, no study has combined multiple ECG parameters to create an ECG model for dementia prediction. Purpose Using data from the ARIC study, a prospective community-based cohort of Black and White participants in the USA that started in 1987-89, we created an ECG model (based on 7 pre-defined ECG parameters linked to dementia) and compared its model discrimination with the UKBDRS. Methods Participants without prevalent dementia from 2 baselines were included: Visit 4 (V4, 1996-98) and V5 (2011-13). Seven ECG parameters were examined: heart rate, abnormal P-wave terminal force in lead V1 (PTFV1), prolonged P wave duration, abnormal P wave axis, advanced interatrial block, left ventricular hypertrophy (LVH, Cornell voltage criteria), and corrected QT interval (QTc). Dementia cases were identified through 2019 using in-person and phone cognitive assessments, hospitalisation codes, and death certificates. Using a backward selection method (keeping variables with P<0.10 and age, since it is an important dementia risk factor), parsimonious Cox regression models were constructed for prediction of dementia over the longest available follow-up (V4: 23 years, V5: 8 years). Model discrimination of the ECG models and UKBDRS variables was evaluated by the Harrell’s C-statistic (95% CI). Results At V4, 11,520 participants (mean age, 62.8 ± 5.7 years; 56% women; 22% Black) were included; 2,427 developed dementia. At V5, 5,667 participants (mean age, 75.4 ± 5.1 years; 59% women; 22% Black) were included; 830 developed dementia. Figures 1 and 2 show the C-statistic (95%) and area under the ROC curve for the ECG model and UKBDRS variables at V4 and V5, respectively. The C-statistic (95% CI) for both ECG models were >0.70 and comparable with the corresponding UKBDRS models. Conclusion For middle-aged and older adults, a dementia prediction model comprising age and 4 ECG variables has good discrimination for dementia that is comparable with the 12-variable UKBDRS model. Since ECG variables are easily obtainable and objectively measured, these ECG models will be easier to adopt than the UKBDRS model. Further work to validate this model in an external cohort and develop a risk score will facilitate clinical translation.

P-wave terminal force is related to left pulmonary vein reconnection in patients with atrial fibrillation recurrence after pulmonary vein isolation.

In patients with atrial fibrillation (AF) recurrence after pulmonary vein (PV) isolation, noninvasive markers predicting PV reconnection or PV reconnection sites have not been fully elucidated. This study investigated the relationship between the P-wave terminal force in lead V1 (PTFV1) and the PV reconnection or reconnection site in patients with AF recurrence. We retrospectively studied consecutive patients who underwent second AF ablation between April 1, 2018, and June 1, 2023. PTFV1 was investigated before the first AF ablation (pre-ablation PTFV1) and before the second AF ablation (post-ablation PTFV1). In addition, we examined the ratio of the post-ablation to pre-ablation PTFV1 (PTFV1 ratio). These values were compared between patients with and without PV reconnection, with and without left PV (LPV) reconnection, and with and without right PV (RPV) reconnection. The analysis included 56 patients. PTFV1 was reduced because of the first AF ablation. In addition, the values were more decreased in patients without PV reconnection than with PV reconnection. The PTFV1 ratio was significantly smaller in the patients without LPV reconnection than with LPV reconnection; no significant difference was observed between the patients with and without RPV reconnection. Receiver operating characteristic curve analysis showed that a PTFV1 ratio > 0.69 predicted LPV reconnection with 70.0% sensitivity and 66.7% specificity. In conclusion, the PTFV1 ratio may be a noninvasive marker predicting LPV reconnection in patients with AF recurrence.

The Role of P Wave Parameters in Predicting Pulmonary Vein Isolation Outcomes for Paroxysmal Atrial Fibrillation: An Observational Cohort Study.

Pulmonary vein isolation (PVI) is an effective management method for paroxysmal atrial fibrillation (PAF). The P wave in the 12-lead electrocardiogram (ECG) represents atrial depolarisation. This study aims to utilise the P wave to predict PVI outcomes for PAF. This single-centre retrospective study aimed to predict PVI outcomes using P wave parameters. It included 211 consecutive patients with first PVI for PAF between 2018 and 2019 and targeted the pulmonary veins (PVs). Procedure success was defined by freedom of ECG-documented AF at 12 months. Digital 12-lead ECGs with 1-50 hertz bandpass filters were monitored before the procedure. Corrected P wave duration (PWDc), P wave amplitude (PWV), P wave dispersion (PWDisp), intra-atrial block (IAB), P wave area (PWA), and P wave terminal force in V1 (PTFV1) were measured before ablation and correlated with the outcomes. Successful PVI occurred in 154 patients (73%). Demographics were similar between both arms. P wave parameters correlated with PVI failure included increased PWDc in all leads except for lead III, aVR, and V3, decreased PWV in lead I (hazard ratio [HR]: 0.7, 95% confidence interval [CI]: 0.53-0.95), lead II (HR: 0.45, 95% CI: 0.22-0.65), aVL (HR: 0.58, 95% CI: 0.22-0.98), and aVF (HR: 0.67, 95% CI: 0.58-0.87), decreased PWA in lead I (HR: 0.55, 95% CI: 0.21-0.76), lead II (HR: 0.48, 95% CI: 0.34-0.87), aVL (HR: 0.65, 95% CI: 0.45-0.96), and aVF (HR: 0.61, 95% CI: 0.32-0.89), and the presence of IAB (HR: 2, 95% CI: 1.4-4.2, p = 0.02). PWDisp and PTFV1 were not correlated with PVI outcome. PWDc, PWA, PWV, and IAB are valuable predictors for PVI outcome for PAF at 12 months.

Atrial cardiopathy biomarkers and atrial fibrillation in the ARCADIA trial.

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. 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. 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. Biomarkers used to identify atrial cardiopathy in ARCADIA were moderately predictive of subsequent AF.

Exploring the impact of electrocardiographic parameters on the risk of common arrhythmias: a two-sample Mendelian randomization study.

Observational studies have shown that heart rate (HR), heart rate variability (HRV), P-wave terminal force, P-wave duration, T-wave amplitude and PR interval are associated with risk factors for atrial fibrillation (AF) or bradycardia. Arrhythmias are associated with many causes of hospitalization. However, observational studies are susceptible to confounding factors that have not yet been identified. The objective of this study was to clarify the causal relationships by Mendelian randomization analysis. We conducted a two-sample and multivariate Mendelian randomization (MVMR) analysis using genome-wide association study (GWAS) data from a European population to assess the total and direct causal effects of HR, three HRV traits, P-wave terminal force, P-wave duration, T-wave top amplitude in five-lead modes, and the PR interval on the risk of AF (N=191,205), bradycardia (N=463,010), and supraventricular tachycardia (SVT) (N=463,010). The results of the univariate MR analysis revealed the following significant causal effects: the higher the genetically predicted PR interval, the lower the risk of AF; the higher the HR and T-wave top amplitude (aVR leads and V3 + V4 + aVL leads), the lower the risk of bradycardia; and the higher HR and the lower PR interval, the higher the risk of SVT. The multivariate MR results indicated that the HRV_standard deviation of the normal-to-normal (SDNN) interval had an independent causal effect on the risk of AF [odds ratio (OR): 0.515; 95% confidence interval (CI): 0.278-0.954; P=0.03], and the T-wave top amplitude in the aVR leads (OR: 0.998; 95% CI: 0.996-0.999; P<0.001) and the HRV_SDNN (OR: 0.988; 95% CI: 0.976-1.000; P=0.045) had independent causal effects on the risk of bradycardia. The HRV_SDNN had an independent causal effect on AF, while the HRV_SDNN and T-wave top amplitude in the aVR leads had independent causal effects on bradycardia, which suggests that some of the electrocardiographic parameters have preventive effects on the incidence of AF and bradycardia.

Association between atrial cardiopathy and stroke severity in acute ischemic stroke

In this hospital-based cross-sectional analytic study, we retrospectively reviewed clinical data of patients with acute ischemic stroke (AIS) between January 2017 and April 2023. Atrial cardiopathy was defined as any presence of the following: left atrial diameter ≥ 52 mm (males) or ≥ 47 mm (females), elevated P-wave terminal force in V1 > 5000 μV ms, or serum N terminal pro B type natriuretic peptide > 250 pg/ml. Initial stroke severity was defined by the National Institutes of Health Stroke Scale (NIHSS; moderate-to-severe, ≥ 5; and severe, ≥ 15). Univariate and multivariate binary logistic regression analyses were performed to assess the association between atrial cardiopathy and stroke severity. Among 662 AIS patients (mean age 70 years [interquartile range 61–78], 31.3% women), 303 (45.8%) had atrial cardiopathy. Multivariable logistic regression analysis showed that the presence of atrial cardiopathy was significantly associated with a higher odd of moderate-to-severe stroke (adjusted odds ratio [OR] 2.16, 95% confidence interval [CI] 1.46–3.20, p < 0.001) and severe stroke (adjusted OR 4.89, 95%CI 2.45–9.76, p < 0.001). This association remained significant in a sensitivity analysis excluding those with atrial fibrillation or coronary artery disease. Findings of the current study revealed that the association of atrial cardiopathy was with initial stroke severity independent of atrial fibrillation and was even confirmed in patients without atrial fibrillation; future studies to explore improved stroke prevention strategies for patients with atrial cardiopathy are needed.

ATRIAL CARDIOMYOPATHY AND STROKE PREVENTION - REVIEW

Atrial cardiomyopathy (ACM) represents a novel paradigm in cardiovascular medicine, encompassing structural and functional changes within the atria that contribute to adverse clinical outcomes, notably stroke. This review explores the multifaceted implications of ACM, particularly its relevance independent of atrial fibrillation (AF) and its potential applications in stroke prevention and management. Advancements in imaging modalities, notably speckle-tracking echocardiography, offer valuable insights into atrial remodeling and dysfunction, facilitating early detection of ACM. Markers such as P-wave terminal force, NT-proBNP levels, and left atrial dimensions serve as diagnostic indicators for ACM, aiding in risk stratification in individuals devoid of AF history. Ischemic strokes are one of the most common causes of cardiovascular morbidity and mortality. A significant proportion of patients with ischemic stroke are suspected of embolic stroke without a specific embolic source being found (ESUS). The most recent related clinical trials evaluated tailored anticoagulation strategies in ACM-associated stroke, signaling a shift beyond conventional AF management. In conclusion, ACM emerges as a pivotal concept in stroke prevention, offering opportunities for personalized interventions and refined risk stratification beyond AF.

Interatrial block and abnormal P-wave electrocardiographic parameters as non-invasive predictors of atrial fibrillation

Aim. To identify noninvasive markers of atrial electrical dysfunction and risk of nonvalvular atrial fibrillation (AF) and to develop a predictive mathematical model to estimate the AF risk based on electrocardiographic (ECG) P-wave parameters during sinus rhythm.Methods. The study included 211 patients with cardiovascular pathology (aged median 62 [52; 71] years, 67.8% male, NYHA heart failure class I-III). All patients (follow-up median 45 [26; 67] months) underwent a complex of studies: 12-lead ECG, echocardiography, 24-hour ECG monitoring. Based on surface ECG data during sinus rhythm, parameters of atrial electrical activation were assessed such as Morphology, Voltage and P waves duration (MVP) according to integral analysis by MVP score.Results. During 3.7-year period, 44 (20.8%) patients experienced new-onset sustained AF and 12 (5.69%) patients developed ischemic stroke. As a result of ROC analysis and univariate Cox regression, independent predictors of AF were identified: P-wave prolongation in the DII lead, 3rd degree or advanced interatrial block (aIAB), an increase P-wave terminal force in lead V1 (PTFV1), low-voltage P-wave in the DI lead and сalculated level of abnormal P-wave ≥3 points on the MVP score. Data from multivariate Cox proportional hazards regression analysis confirmed the prognostic significance for three independent predictors of AF: aIAB (hazard ratio (HR) 5.92; 95% confidence interval (CI) [2.48-4.12]; p=0.0001); PTFV1 (HR 1.14; 95% CI [1.04-1.24], p=0.003); low-voltage P-wave in lead DI &lt;0.1 mV (HR 1.03; 95% CI [1.02-1.05]; p=0.0001); and as a result a mathematical model was created to predict AF risk (-2LL =258; χ2=105; p=0.0001). Predictors such as PTFV1 (HR 1.41; 95% CI [1.17-1.72], p=0.0001) and MVP score of abnormal P-waves (HR 1.85; 95% CI [1.27-1.72] 2.70], p=0.001) were associated with a high risk of stroke according to Cox regression model (-2LL= 62.5; χ2=38.4; p &lt;0.001).Conclusion. Complex of ECG markers of atrial electrical dysfunction such as aIAB, PTFV1, level MVP score of abnormal P-wave and low P-wave voltage allows identifying patients at high risk of AF and ischemic stroke.

Catheter ablation of atrial fibrillation shows pulmonary vein dependent effect on the signal-averaged P-wave morphology

Abstract Background and Aims Cryoballoon ablation of atrial fibrillation alters a significant amount of vital myocardium that contributes to its electrical activity. However, the impact of pulmonary vein isolation (PVI) on P-wave morphology is unclear. The aim of this investigation was to quantify whether the contribution of the left or right pulmonary veins (PVs) is greater using means of signal-averaged P-wave analysis. Methods Unfiltered high-resolution (2000 samples/second) ECGs were obtained for 5 minutes both pre- and post-isolation of the left and right PVs, with 12 standard and 10 additional leads (x01-x10). Additional lead positions were determined in prior studies for optimal detection of atrial electrical activity not captured by standard leads. Signal-averaged ECGs were computed and analyzed using bespoke software in Matlab. Statistical significance was assessed using a two-tailed paired t-test. A total of 69 participants were screened for the study. For the analysis, 64 participants with sinus rhythm in all ECG recordings were eligible. Results Significant postablation changes for various ECG parameters across different lead combinations were found (Table 1). On average, after ablation of the left pulmonary veins (LPVs), there was a reduction in P-wave terminal force (3.07±2.05 mV*ms vs. 2.84±1.88 mV*ms, p = 0.044), P-wave complexity (2.02±0.64 vs. 1.90±0.57, p = 0.047), and sample entropy (0.210±0.039 au vs. 0.197±0.031 au, p &amp;lt; 0.001), whereas P-wave duration (148.24 ms vs. 153.23 ms, p &amp;lt; 0.001) and PQ time (200.41 ms vs. 205.43 ms, p &amp;lt; 0.001) prolonged. However, after ablation of the right pulmonary veins (RPVs), sample entropy decreased (0.196±0.031 au vs. 0.190 ±0.027 au, p = 0.049) and amplitude increased (0.087±0.024 mV vs. 0.091±0.024 mV, p = 0.002). Conclusion PVI in atrial fibrillation has a significant effect on signal-averaged P-wave. These effects are more pronounced after ablation of the LPVs than the RPVs. Parameters such as PWTF, PWC and SaE demonstrate potential to assess the effect of catheter ablation and may serve as a potential indicator for a successful procedural outcome.

Higher recurrence rate after ablation of persistent atrial fibrillation in patients with prolonged P-wave negativity in lead V1

Abstract Background Several ECG P-wave parameters, such as duration, amplitude and morphology reflect the electromechanical condition of the atria. P-wave features mainly served to identify patients prone to atrial fibrillation (AF) or to predict recurrence of paroxysmal AF after ablation. Purpose We sought to investigate which specific features derived from the P-wave might help identify patients with persistent atrial fibrillation (peAF) unresponsive to wide circumferential pulmonary veins isolation (WPVI). Methods 41 patients (63±10 y) with peAF (sustained duration 11±7 months) underwent a de-novo WPVI. A second WPVI was performed in patients with recurrent AF in order to provide complete PV disconnection. We defined "success" as patients who remained in sinus rhythm (SR) after one or two procedures, and "failure" otherwise. The average duration and amplitude of the P-waves on ECG lead II, and the duration and amplitude of positive and negative deflections on ECG lead V1 were extracted during SR after cardioversion at the end of the index WPVI. P-wave terminal force in V1 (PTFV1) was computed as the product of negative amplitude and duration in lead V1. Results Over a mean follow-up of 32±9 months, 24 patients remained free from AF (success group), while 11 patients had AF recurrence after 2 WPVIs (failure group). Six patients were lost to follow-up or declined the second WPVI. 45% (5/11) were ON antiarrhythmic drugs (AAD) during follow-up in the failure group, while 0.04% (1/24) were ON AAD in the success group (p&amp;lt;0.05). Other clinical characteristics (e.g. age, body mass index, left atrial volume or duration in sustained AF) were similar. The figure displays P-wave metrics of patients ON and OFF AAD during follow-up. No significant differences were found in P-wave duration (lead II; Panel A1), in PTFV1 (Panel A2), and in duration of V1 positive deflection (Panel A3). Interestingly, the failure group displayed longer duration of the negative deflection in V1 (76±17ms) than that of the success group (68±18ms, p&amp;lt;0.05; Panel A4). Panel B shows that the differences remained after exclusion of patients ON AAD during follow-up. No differences were found in P-wave amplitude in lead II or in amplitude of positive and negative deflections in lead V1 (data not shown). Conclusion Our results show that prolonged negativity in lead V1, which is indicative of left atrial electromechanical remodeling, is associated with failure to restore long-term sinus rhythm after WPVI of peAF.

Dietary sodium intake and atrial myopathy

Abstract Background Diagnostic markers associated with atrial cardiomyopathy, a precursor state to atrial fibrillation (AF), include premature atrial complex (PACs) frequency, left atrial volume index (LAVi) and p-wave indices. Life-style factors associated with atrial myopathy markers are insufficiently studied. Sodium intake is a modifiable risk factor for hypertension, cardiovascular disease and AF. Purpose We aimed to study the association between sodium intake and atrial myopathy markers in the population-based multicenter Swedish CArdioPulmonary bioImage Study. Methods We included 5,309 randomly invited 50–65-year-olds at the Malmö (n=1,125,) and Uppsala sites (n=4,184) without AF who had contributed a 24hECG and a fasting morning urine sample, from which daily sodium intake was estimated using the Kawasaki formula. At the Malmö site resting ECGs from which P-wave indices could be measured were available in 1,066 individuals, and LAVi was available in a random subsample (n=357). The association between sodium intake and atrial myopathy markers was modeled adjusted for age, sex, body mass index, smoking, systolic blood pressure, antihypertensive treatment, coronary artery disease, and heart failure using negative binomial regression for PAC frequency, linear regression for P-wave duration and LAVi and logistic regression for P-wave terminal force in V1, all using sodium intake as a continuous variable and strata at &amp;lt;2, 2.0-2.99g, 3.0-3.99g, 4.0-4.99g and ≥5 g/day, with 3.0-3.99 as the reference category. We also modeled the association between sodium intake and PACs using restricted cubic splines. Results The mean age was 58.1 (±4.1) years, and 52.7% were female. The mean estimated sodium intake was 3.3 (±1.4) g/day. Mean 24h PAC count was 27, 4.7% had ≥500 PACs. High sodium intakes were associated with increased PAC frequency, of 14% (95% confidence interval (CI 1-29% p=0.03)) for 4.0-4.99g/day and 25% (95%CI 8-45%, p=0.002) for intakes ≥5.0g/day, compared to sodium intakes of 3.0-3.99 g/day. There was no significant association between low sodium intakes (&amp;lt;3.0 g/day) and PACs, Figure 1. Sodium intakes of 4.0-4.99 g/day were associated with increased P-wave duration, ß-coefficient 2.4 (95%CI 0.3-4.1, p=0.03), compared to 3.0-3.99g/day, but there was no association between sodium intakes and LAVi, or P-wave terminal force in V1, either as a continuous variable or in strata. Conclusion High dietary sodium intake is associated with PAC frequency, a known prediction of AF and stroke. Whether reduced sodium diets could reduce PAC frequency, and whether that would impact AF and stroke risk needs further study.Sodium intake and PAC frequency

Electrocardiogram prediction of atrial fibrillation risk after stroke: A protocol for systematic review and meta-analysis.

Atrial fibrillation (AF) is one of the most common clinical arrhythmias. This study aims to predict the risk of post-stroke AF through electrocardiographic changes in sinus rhythm. We searched the MEDLINE (PubMed) and EMBASE databases to identify relevant research articles published until August 2023. Prioritized items from systematic reviews and meta-analyses were screened, and data related to AF detection rate were extracted. A meta-analysis using a random-effects model was conducted for data synthesis and analysis. A total of 32 studies involving electrocardiograms (ECG) were included, with a total analysis population of 330,284 individuals. Among them, 16,662 individuals (ECG abnormal group) developed AF, while 313,622 individuals (ECG normal group) did not. ECG patterns included terminal P-wave terminal force V1, interatrial block (IAB), advanced interatrial block, abnormal P-wave axis, pulse rate prolongation, and atrial premature complexes. Overall, 15,762 patients experienced AF during the study period (4.77%). In the ECG abnormal group, the proportion was 14.21% (2367/16,662), while in the control group (ECG normal group), the proportion was 4.27% (13,395/313,622). The pooled risk ratio for developing AF was 2.45 (95% confidence interval [CI]: 2.02-2.98, P < .001), with heterogeneity (I2) of 95%. The risk ratio values of alAB, P-wave terminal force V1, interatrial block, abnormal P-wave axis, pulse rate prolongation and atrial premature complexes were 4.12 (95% CI, 2.99-5.66), 1.47 (95% CI, 1.19-1.82), 2.54 (95% CI, 1.83-3.52), 1.70 (95% CI, 0.98-2.97), 2.65 (95% CI, 1.88-3.72), 3.79 (95% CI, 2.12-6.76), respectively. There is a significant correlation between ECG patterns and the occurrence of AF. The alAB exhibited the highest level of predictability for the occurrence of AF. These indicators support their use as screening tools to identify high-risk individuals who may benefit from further examinations or empirical anticoagulation therapy following stroke.

The clinical value of P-wave terminal force in lead V1 in evaluating pericardial thickness in tuberculous constrictive pericarditis

AimTo investigate the relationship between p wave terminal force (Ptfv1) and pericardial thickness in patients with tuberculous constrictive pericarditis.MethodsFrom January 2018 to October 2022, 95 patients with tuberculous constrictive pericarditis who needed pericarditis dissection in a hospital were collected, and 3 patients who did not meet the criteria were excluded, a total of 92 cases. The absolute value of Ptfv1 in conventional electrocardiogram was tested before surgery, and pericardial thickness was measured by echocardiography and chest CT. Pericardial thickness was measured after pericardial dissection. Pearson correlation analysis was used, R software was used to make scatter plot, and non-parametric square test was used. The correlation of postoperative measurements with echocardiography, chest CT and absolute value of Ptfv1 was analyzed.ResultsPearson correlation analysis was conducted with postoperative measurements and echocardiography measurements, postoperative measurements and chest CT measurements, and postoperative measurements and absolute value of Ptfv1. Pearson correlation analysis showed that the correlation coefficients between postoperative measurements and echocardiography, chest CT and Ptfv1 values were statistically significant. Scatter plot and nonparametric Chi-square test showed that postoperative measurements were consistent with absolute values of echocardiography, chest CT and Ptfv1 (p < 0.05). And this study found that the distribution of the value of Ptfv1 ≥ 5 was higher than the value of Ptfv1 < 5 after pericardiectomy (0.95:0.05) in the absolute value of Ptfv1 ≥ 0.04 which measured before pericardiectomy. The hypothesis was statistically significant (p < 0.05).ConclusionThe absolute value of Ptfv1 in electrocardiogram can be used as an auxiliary diagnostic index to evaluate pericardial thickness in tuberculous constrictive pericarditis.

Apixaban to Prevent Recurrence After Cryptogenic Stroke in Patients With Atrial Cardiopathy

Atrial cardiopathy is associated with stroke in the absence of clinically apparent atrial fibrillation. It is unknown whether anticoagulation, which has proven benefit in atrial fibrillation, prevents stroke in patients with atrial cardiopathy and no atrial fibrillation. To compare anticoagulation vs antiplatelet therapy for secondary stroke prevention in patients with cryptogenic stroke and evidence of atrial cardiopathy. Multicenter, double-blind, phase 3 randomized clinical trial of 1015 participants with cryptogenic stroke and evidence of atrial cardiopathy, defined as P-wave terminal force greater than 5000 μV × ms in electrocardiogram lead V1, serum N-terminal pro-B-type natriuretic peptide level greater than 250 pg/mL, or left atrial diameter index of 3 cm/m2 or greater on echocardiogram. Participants had no evidence of atrial fibrillation at the time of randomization. Enrollment and follow-up occurred from February 1, 2018, through February 28, 2023, at 185 sites in the National Institutes of Health StrokeNet and the Canadian Stroke Consortium. Apixaban, 5 mg or 2.5 mg, twice daily (n = 507) vs aspirin, 81 mg, once daily (n = 508). The primary efficacy outcome in a time-to-event analysis was recurrent stroke. All participants, including those diagnosed with atrial fibrillation after randomization, were analyzed according to the groups to which they were randomized. The primary safety outcomes were symptomatic intracranial hemorrhage and other major hemorrhage. With 1015 of the target 1100 participants enrolled and mean follow-up of 1.8 years, the trial was stopped for futility after a planned interim analysis. The mean (SD) age of participants was 68.0 (11.0) years, 54.3% were female, and 87.5% completed the full duration of follow-up. Recurrent stroke occurred in 40 patients in the apixaban group (annualized rate, 4.4%) and 40 patients in the aspirin group (annualized rate, 4.4%) (hazard ratio, 1.00 [95% CI, 0.64-1.55]). Symptomatic intracranial hemorrhage occurred in 0 patients taking apixaban and 7 patients taking aspirin (annualized rate, 1.1%). Other major hemorrhages occurred in 5 patients taking apixaban (annualized rate, 0.7%) and 5 patients taking aspirin (annualized rate, 0.8%) (hazard ratio, 1.02 [95% CI, 0.29-3.52]). In patients with cryptogenic stroke and evidence of atrial cardiopathy without atrial fibrillation, apixaban did not significantly reduce recurrent stroke risk compared with aspirin. ClinicalTrials.gov Identifier: NCT03192215.