Sinus Rhythm Research Articles

Sinus rhythm maintenance and the changes of echocardiographic parameters in patients with late persistent atrial fibrillation at 6 months after direct current cardioversion

Abstract Background Late persistent non-valvular atrial fibrillation (AF), with a duration of its episode ≥90 days and up to 12 months, is considered a distinct persistent AF entity, which might possess substantial differences as compared to its early persistent pattern (up to 3 months) in terms of myocardial remodeling and its reversibility after cardioversion. Purpose To study the changes of echocardiographic parameters in patients with non-valvular late persistent AF with respect to sinus rhythm (SR) maintenance at 6 months after successful direct current cardioversion (DCCV). Methods The cohort single-center study enrolled 59 late persistent AF patients, who underwent a successful elective DCCV. At 6-months follow-up, patients were subdivided into the groups regarding SR maintenance: 32 (54 %%) patients with a maintained SR (G1), and 27 (46 %) patients with a failure to maintain SR (G2). The parameters of myocardial remodeling and function were evaluated by transthoracic (TTE) and transesophageal echocardiography (TEE) baseline (by TTE and TEE) and at 6-months follow-up (by TTE). Results TTE data from G1 patients, in contrast to G2, suggested better baseline status of left heart chambers, particularly the lower diameter of left atrium (LA), left ventricular (LV) end-diastolic and end-systolic volumes and higher LV systolic function (by LV ejection fraction [EF]). According to the TEE data, G2 (vs. G1) was characterized by more prevalent cases of LA spontaneous (echo) contrast (41 % vs. 15 %, respectively; p=0,042) and LA appendage flow velocity ≤40 cm/s (82 % vs. 53 %, respectively; p=0,022). At 6-months follow-up TTE, G1 patients, as opposed to G2, demonstrated a better profile of echocardiographic parameters, namely a lower LA diameter, LA and right atrium (RA) volumes, along with less advanced LV remodeling and higher LV EF. TTE data from G1 at 6-months follow-up after DCCV suggested the reverse remodeling of both atria, namely the decrease of LA diameter, LA volume and its index (Fig. 1), as well as RA volume and its index. Moreover, G2 demonstrated a decline in LV systolic function, in particular the rise of LV end-systolic volume and decrease of LV EF (Fig. 2), as compared to G1. Furthermore, at 6-months follow-up, G2 patients presented with more advanced severity of PH and tricuspid regurgitation, in comparison with G1. Conclusions Late persistent AF patients with a SR maintenance at 6-months follow-up after successful DCCV presented a better baseline profile of myocardial remodeling and systolic function. The SR maintenance at 6-months follow-up after DCCV was associated with the reverse remodeling of left heart chambers (LA and LV) and RA. On the contrary, a failure to maintain SR in late persistent AF patients was associated with a deterioration in LV systolic function, and more advanced PH and tricuspid regurgitation.

Presence of Atrial Fibrillation (AF) is a poor prognostic marker in patients with Heart Failure with reduced Ejection Fraction (HFrEF) and Left Bundle Branch Block (LBBB)

Abstract Background Observational data indicate that between 20-30% of patients with HFrEF have LBBB. While numerous independent variables are implicated in the overall prognosis of these patients, this group of patients respond poorly to medical therapy. Presence of AF further impairs the functioning of the left ventricle by several mechanisms e.g., left atrial dilatation, decreased left ventricular filling, irregular cycle length, functional mitral regurgitation etc. Literature is sparse on the cumulative effect of AF in this group of patients. Purpose To assess the effect of AF on left ventricular ejection fraction (LVEF) and mortality in patients presenting with HFrEF and LBBB Methods Single centre, retrospective, observational study over 33 months (Jan 2021 – Sept 2023). Patients with HFrEF and LBBB (as defined by the European Society of Cardiology, 2021) identified from the heart failure database. Results (Table) N=80 Whole cohort: age 74.8 +/- 13.6 years (median:79, range 39-96); 57/80 (67.5%) males. Hypertension [41/80 (51.3%)] was most common comorbidity. Majority were on 3 drugs (23/80, 28.8%) of guideline directed medical therapy (GDMT) with ~1 in 4 patients [19/80 (23.8%)] on all 4 drugs. 32/80 (40.0%) were in AF, remainder in sinus rhythm (SR). Mean baseline LVEF: 21.8 +/- 8.4. Mean LVEF continued to be ≤35% (paired echocardiograms available in 50.0% patients) inspite of GDMT. The QRS duration continued to prolong on follow-up. Patients in AF were statistically significantly older, were less often on all 4 GDMT drugs (particularly sodium glucose transporter 2 inhibitors - SGLT2i’s), and were less likely to survive than those in SR. No difference in comorbid conditions or QRS prolongation on follow-up were seen between patients with AF versus SR. There was trend towards a larger increase in mean LVEF in patients with SR than AF. Conclusions In our experience, patients with HFrEF and LBBB continue to have a high mortality (45.0% at ~ 3 years) inspite of GDMT. AF is seen in a high percentage of patients (40.0%) in this cohort, worsening the prognosis further, with mortality nearly 3 times higher than those in SR. Aggressive management of patients with HFrEF and LBBB with, where indicated, early cardiac resynchronisation therapy (CRT) and more so, of those with AF (with +/- atrioventricular node ablation or left atrial ablation) should be considered at an early stage after diagnosis.Table

Association between CHA2DS2-VASc score and left atrial function by speckle tracking echocardiography in patients with sinus rhythm

Abstract Background The CHA2DS2-VASc score is a scoring system that was first used for the risk assessment of cerebrovascular or thromboembolic events in patients with atrial fibrillation (AF). The factors that constitute the CHA2DS2-VASc scoring system can all individually have an impact on LA function. The application of this scoring system can also be applied to patients without AF. The LA structural remodeling and/or functional impairment play a part in the pathogenesis and development of AF and independent of rhythm, may result in atrial hemostasis and confer a prothrombotic diathesis, resulting in thromboembolic stroke. Speckle- tracking echocardiography (STE) makes it possible to measure LA function with relatively high accuracy and at the very early stage even in the absence of LA enlargement. Purpose The aim of our study was to assess the left atrial function in patients with sinus rhythm with different CHA2DS2-VASc scores (low, moderate and high) by speckle tracking echocardiography and to identify the association between them. Methods This study was conducted using prospectively collected data (1st May, 2022 to 30th October 2022) from patients with sinus rhythm and different CHA2DS2-VASc scores (50 Low risk score patients (1 for females and 0 for males), 50 moderate risk score patients (2 for females and 1 for males) and 50 high risk score patients (≥3 for females and ≥2 for males) After obtaining an informed consent, all volunteers underwent thorough history taking, 12 lead ECG and conventional transthoracic echocardiography and speckle-tracking echocardiography. Results LA strain during the reservoir (LASr) and conduit phases (LAScd) were statistically significantly lower in the high-risk score group (33.2 ± 7.1 and 20.3 ± 5.7) than the moderate-risk score group (36.9 ± 6.1 and 23.5 ± 4.8, p = 0.005 and 0.003 respectively) and low -risk score group (40.6 ± 5.6 and 26.9 ± 3.9, p < 0.001). In addition, LASr and LAScd were statistically significantly lower in moderate- risk score group (36.9 ± 6.1 and 23.5 ± 4.8) than the low -risk score group (40.6 ± 5.6 and 26.9 ± 3.9 ,p=0.007 and 0.001 respectively). Conclusion Higher CHA2DS2-VASc scores were associated with decreased LA strain during the reservoir and conduit phases as markers of LA function with relatively high accuracy and at the very early stage even in the absence of LA enlargement.

The impact of ethnicity on clinical outcomes in patients with heart failure and atrial fibrillation

Abstract Introduction Heart failure (HF) and atrial fibrillation (AF) are increasingly prevalent and associated with substantial morbidity (1,2). When HF and AF co-exist, the outcome profile is significantly worse than for either condition in isolation (3). Ethnic background is known to influence disease outcomes and treatment efficacy (4), but there is limited knowledge about how HF, AF and ethnicity interact on mortality and hospital admission. Purpose This study aims to address the null hypothesis of no difference in death and cardiovascular events comparing non-white and white patients with HF and concomitant AF, and assess the differential impact of ethnicity in patients with these conditions. Methods Individual patient data were obtained from 12 randomized controlled trials (RCTs) in patients with HF. RCT data were harmonised and meta-analysed to investigate the interaction of baseline heart rhythm (sinus rhythm versus atrial fibrillation) and ethnicity (non-white versus white). The primary outcome of all-cause mortality and secondary outcome of cardiovascular (CV)-related mortality were analysed using adjusted Cox regression models and propensity-score matching. Results 16,713 HF patients were included of which 1,899 (11%) were non-white, median age 66 (interquartile range [IQR] 57-73) and 4,703 (28%) women. During median follow-up of 1.4 years (IQR 0.8-2.3), death occurred in 394 (21%) non-white patients and 2,142 (15%) white patients; adjusted hazard ratio (HR) 1.36, 95% CI 1.20-1.54; p<0.001. The impact of ethnicity was greater in patients with coexisting HF and AF (non-white versus white HR 2.05; 95% CI 1.55-2.70; p<0.001), than in those with HF in sinus rhythm (non-white versus white HR 1.24; 95% CI 1.08-1.41; p=0.002). A significant interaction was evident between ethnicity and rhythm status for all-cause mortality (p=0.003), with similar findings using propensity-score matching (Figure 1). An exploratory analysis of beta-blockers versus placebo demonstrated divergent efficacy with respect to mortality for non-white (HR 1.00, 95% CI 0.79-1.27; p=0.99) and white patients (HR 0.70, 95% CI 0.63-0.78; p<0.001); p-interaction=0.008 (Figure 2). For cardiovascular hospitalisation, the non-white cohort also had higher rates, with greatest disparity in patients with combined HF and AF (non-white versus white HR 1.80, 95% CI 1.63-2.37; p<0.001) compared to HF in sinus rhythm (non-white versus white HR 1.23, 95% CI 1.11-1.36; p<0.001); p-interaction=0.012 in propensity-matching. Conclusion Non-white patients with HF suffer from substantially higher rates of death and hospitalisation than corresponding white patients, with the presence of comorbid AF significantly worsening this ethnicity-related disparity. In those with HF in sinus rhythm, beta blockers were found to be significantly less effective at reducing mortality in non-white patients.Figure 1 Figure 2

Characteristics associated with prevalent atrial fibrillation and risk profile for future atrial fibrillation among those in sinus rhythm in an elderly population in the ELSA Brasil Study

Abstract Background Atrial fibrillation (AF) is an arrhythmia that can lead to limiting symptoms and increases the risk of stroke and heart failure (HF). Purpose To evaluate the association of clinical, electrocardiographic, and echocardiographic parameters with prevalent AF or flutter (AFF), and the risk profile for future AFF according to Charge-AF and EHR scores in an elderly population. Methods The ELSA-Brasil is a prospective cohort study designed to investigate cardiovascular disease and diabetes in 15,105 men and women, civil servants from universities or research institutions in six cities of Brazil. We included all participants in ELSA-Brasil aged 60 and over whose diagnosis of AFF could be assessed and had echocardiography performed at the study's baseline. From the initial sample with participants ≥ 60 years (n = 3,263), 400 participants were excluded due to missing data about AFF, and 775 who did not have echocardiographic studies. Results There were 88 (4.2%) participants with AFF at baseline among the 2,088 (65 ± 4.1 years; 53% women) included in this analysis. Those with AFF were older (66.8 ± 4.4 vs 65 ± 4.0 y-o) and had a higher prevalence of HF (16% vs 3.1%), previous myocardial infarction (14.8% vs 3.8%), left bundle branch block (LBBB: 4.6% vs 0,9%), prolonged QT interval (7.9% vs 2.0%), supraventricular extrasystoles (4.6% vs 1.2%), and sinus bradycardia (11.3% vs 2.9%). AFF individuals also presented larger left atrial volume index - LA (33.3 mL/m2 versus 27 mL/m2), left ventricular end-diastolic diameter (4,63 ± 0,6 cm versus 4,47 ± 0,4 cm) and lower left ventricular ejection fraction (LVEF: 63.6 ± 9.1% vs 67.4 ± 6.4%) that non-AFF (all p-values <0.05). In multivariable analysis, prevalent HF, LBBB, larger LA, and lower LVEF were independently associated with the presence of AFF. Among those in sinus rhythm at study baseline, both risk models showed that most individuals in our sample were at low risk. In the Charge-AF, 63% of individuals were identified as presenting low risk (<2.5%), and 12% of the sample was categorized as high risk, with a risk of five-year AFF greater than 5%. Similarly, in the EHR, 67% of participants were classified as low risk, and 13% were considered high risk. Conclusion We found that AFF was present in 4.2% of the subset of older participants in a cohort composed of free-living individuals in Brazil. The presence of AFF was associated with HF history, altered cardiac electrical activity, LA dilation, and worse LV systolic function. Among those with sinus rhythm, 12-13% were considered at high risk of developing AFF (> 5% in five years) based on two clinical scores. Clinical surveillance and monitoring of electrocardiography and echocardiography parameters may help the early identification of risk factors for AFF.

Secretomes from human epicardial adipocytes modulate atrial lymphatics and atrial fibrosis

Abstract Background Cardiac lymphatics maintains myocardial fluid and immune cell homeostasis. Downregulation of cardiac lymphatics leads to cardiac dysfunction through impairment of inflammation and edema. On the other hand, it is well known that adipose tissue accumulation causes lymphatic dysfunction and impairs lymphedema. Purpose We evaluated the expression of atrial lymphatics in human left atrial appendage (LAA) histologically and biologically. Subsequently, we examined secretomes from epicardial adipose tissue (EAT)-derived adipocytes and validated if they change atrial lymphatics expression using ex vivo Organo-culture system. Methods Human LAA samples were collected from forty-two patients during cardiovascular surgery. They were categorized into the sinus rhythm (SR) group (n=16, 73.1±10.4 years), the paroxysmal AF (PAF) group (n=13, 69.8±12.6 years) and the persistent AF (PeAF) group (n=13, 71.2±6.5 years). Human EAT were also excised from patients with and without AF (SR; n=5, AF; n=11) during cardiovascular surgery. Preadipocytes were extracted from EAT by homogenization and collagenase treatment, and cultured to confluence. After differentiation and maturation to adipocytes, cell culture supernatant (CCS) was collected, and was dropped onto the epicardial side of left atrial tissues excised from 8 weeks old male rats for 7 days using an ex vivo organo-culture system. Results In human LAA samples, mRNA expression of lymphangiogenesis-related genes (LYVE1, PROX1, VEGFC, and VEGFR3) was significantly lower in the PeAF group compared to the SR group (p=0.0370, <0.0001, 0.0157, and 0.0009). The number of LYVE1-positive atrial lymphatic endothelial cells (LECs) was also significantly lower in the PeAF group compared to the SR group and the PAF group (p=0.0186 and 0.038). There was a negative correlation between the number of LYVE1-positive atrial LECs and the area percentage of atrial myocardial fibrosis (r=-0.5350, p<0.001). In the experiment using organo-culture system, lymphangiogenesis-related genes expression (Lyve1, Prox1, Vegfc, and Vegfr3) of rat atria treated with CCS of adipocytes from AF patients was significantly lower than those from SR patients (p=0.0391, 0.0100, 0.0034, and 0.0338). Furthermore, the CCS of adipocytes from AF patients contained higher protein levels of leptin, which is known to suppress lymphangiogenesis (p=0.0357). Leptin treatment (100ng/ml) on rat atria also decreased lymphangiogenesis-related genes expression such as Lyve1, Prox1, Vegfc, and Vegfr3 (p=0.0413, < 0.0001, <0.0001, and 0.0190). Conclusions Our study with human LAA demonstrated that atrial lymphatics interact with atrial myocardial fibrosis/progression of AF. Furthermore, our findings indicate that secretomes from EAT-derived adipocytes regulate atrial lymphatics expression, and leptin plays an important role in modulating atrial lymphangiogenesis.

Artificial intelligence (AI)-enhanced electrocardiography: a machine-learning model for differential diagnosis between hypertrophic cardiomyopathy, cardiac amyloidosis and Anderson-Fabry disease

Abstract Background The differential diagnosis between Hypertrophic Cardiomyopathy (HCM) and phenocopies is challenging and relies on a comprehensive approach, which includes clinical and instrumental data, as well as laboratory exams and genetic testing. In this setting, 12-lead electrocardiogram (ECG) represents a valuable tool, but although typical patterns have been described, their diagnostic ability to discriminate between different etiologies is limited and requires considerable clinical experience. However, a correct diagnosis is of pivotal importance, allowing the prompt initiation of phenotype-specific therapies and consequently improving patient survival. Purpose Aim of this study was to develop a machine-learning model based on human-based ECG features to support the differential diagnosis between HCM, Cardiac Amyloidosis (CA) and Anderson-Fabry Disease (AFD). Methods We retrospectively examined ECGs of 200 patients, 50 affected by HCM, 100 affected by CA (50 AL CA and 50 transthyretin CA) and 50 with a diagnosis of AFD cardiomyopathy. The patients were then divided in sinus rhythm (SR) subgroup (158 patients) and atrial fibrillation (AF) subgroup (42 patients). For each subgroup, patients were randomly split into a training (80%) and a testing cohort (20%), and a random forest (RF) model was trained on the training cohort, with hyperparameter tuning via 10-fold cross validation. The resulting model was then tested on the testing cohort to assess its predictive accuracy. Results Both RF models (SR and AF) showed good discriminative performance in this multiclass classification task on the testing cohort [SR: accuracy 67%; multiclass area under the curve (AUC) 0.797, 95% confidence interval (CI) 0.472 -0.827; AF: accuracy 75%; multiclass AUC 0.792, 95% CI 0.349 – 0.968]. Figure 1 and figure 2 report for each model the rank of the most important variables for class prediction. Conclusions An AI-based ECG interpretation based on human-derived ECG features can predict the etiology underlying an hypertrophic phenotype, helping to perform a correct diagnosis and consequently to set a specific therapeutic process.

External validation of a machine learning based classification algorithm for ambulatory heart rhythm diagnostics using smartphone-photoplethysmography - the SMARTBEATS algorithm study

Abstract Introduction Smartphone-photoplethysmography (PPG) can be used for heart rhythm monitoring. According to current guidelines, ECG verification is required for a new diagnosis of atrial fibrillation (AF). Accurate machine learning (ML) based automatic algorithms have the potential to facilitate clinical applications generating large numbers of PPG recordings, by offloading the need for manual over-read. Purpose The aim of this study was to evaluate the diagnostic performance of an automatic ML-based algorithm for heart rhythm diagnostics using smartphone-PPG recorded by patients with AF in an unsupervised ambulatory setting. Methods Patients undergoing direct current cardioversion (DCCV) at a university hospital for treatment of AF or atrial flutter (AFL) were asked to perform one-minute heart rhythm recordings post-cardioversion at least twice daily for 30 days. All participants were provided with an iPhone 7 smartphone running the CORAI Heart Monitor PPG application simultaneously with a single-lead ECG recording (KardiaMobile). The automatic algorithm uses support vector machines (SVM) to classify heart rhythm from smartphone-PPG recordings. The SVM classifier evaluated here was trained on ambulatory PPG recordings made by patients in a separate cardioversion cohort, ensuring complete independence between training and validation sets. PPG recordings in the validation cohort were analyzed by the automatic algorithm and diagnostic performance was calculated by comparing heart rhythm classification output from the SVM classifier to the heart rhythm diagnosis from the simultaneous ECG recordings. ECG recordings were interpreted independently by two cardiologists and were set as gold standard. Results The SVM classifier was trained on data from 153 patients with 11,749 PPG recordings, of which 5,873 (50.0%) were labelled as AF and 5,876 (50.0%) as sinus rhythm (SR), as assessed by manual reading. In the validation cohort, 280 patients, with a median age of 69.0 years (31% women), registered 18,005 simultaneous PPG and ECG recordings. Recordings interpreted as AFL on ECG (2.0%), as having insufficient quality on ECG (4.9%) or PPG (2.8%), and low certainty algorithmic classifications (1.2%) were excluded, leaving 16,057 PPG recordings. Included ECG recordings consisted of 71.2% interpreted as (SR) and 28.8% as AF. Algorithm classification of the PPG recordings in the validation cohort diagnosed AF (sensitivity) in 99.7% and SR (specificity) in 99.7% of the recordings, with an overall accuracy of 99.7%. F1-score was 99.4% and area under the ROC curve (AUC) was 0.999. Conclusion A machine learning based algorithm for automatic heart rhythm diagnostics showed excellent diagnostic performance for smartphone-PPG recordings in an unsupervised ambulatory setting, minimizing the need for ECG verification in cardioversion populations.

Impact of the underlying rhythm during cavotricuspid isthmus ablation on the incidence of future new-onset atrial fibrillation: insights from an international multi-centre registry

Abstract Background Radiofrequency catheter ablation of the cavotricuspid isthmus (RF-CTI) is the estabslished treatment of typical atrial flutter (AFL). After RF-CTI for AFL patients without previously documented atrial fibrillation (AF) may also develop AF. It is unknown whether the presence or absence of AFL at the time of ablation can predict the future occurence of AF. Purpose To compare baseline characteristics, procedural data, and long-term follow-up (FU) of patients with AFL. Methods Consecutive patients with documented AFL undergoing RF-CTI were enrolled in a multi-center registry in five centers in two countries between February 2017 and July 2023. For patients with AFL, entrainment mapping was performed for confirming CTI dependent AFL. Patients were categorized into two groups, those with AFL and those with sinus rhythm (SR) during RF-CTI. FU data were collected, including clinical assessments, 12-lead electrocardiogram (ECG) and 24-hour Holter-ECGs during each visit. Results Of the 949 subjects, 36% were excluded from the analysis due to a history of AF. A total of 574 patients were included (mean age 68 +/- 11 yrs, 14% females), 62% presented in AFL group and 38 % SR group during CTI. Median FU was 364 days. Patients in AFL group were older (P < 0.029), more likely to have diabetes (P = 0.026), and were less frequently treated with antiarrhythmic drugs (P < 0.001). In the first 12 months of FU, 40% of the patients underwent three FU examinations, while 77% of the patients underwent at least one 24-hour Holter-ECGs during FU. In the Kaplan-Meier analysis patients in AFL group significantly less often developed AF during FU (log-rank, P < 0.016, central ). In the multivariate Cox regression analysis, sinus rhythm during ablation (hazard ratio 1.474; 95% CI 1.043-2.084; P = 0.028), male gender (hazard ratio 1.722; 95% CI 1.116-2.658; P = 0.014) and coronary artery disease (hazard ratio 1.711; 95% CI 1.145-2.555; P = 0.009) were identified as predictors for the occurence of AF during FU. Conclusion Over a one year follow-up, new onset AF occurs significantly less frequently in patients with ongoing atrial flutter during RF-CTI ablation.

A novel device for electrocardiographic imaging

Abstract Background Electrocardiographic imaging (ECGi) is a non-invasive imaging tool that allows 3D visualization and characterization of the electrical activity of the heart from measurements on the body surface by solving the so called "inverse problem of electrocardiography". This method helps overcome the limitations of the conventional12-lead ECG in diagnosing and locating heart arrythmias. We developed a textile 34-electrode imageless device (with no need for MRI or CT-scan). Purpose We aim to evaluate the feasibility and safety of the use of a novel textile imageless 34-electrode device for recording ECGi for identification of electrical activity of the heart. Methods and results The performance of a prototype data acquisition system (DAS) was evaluated in 158 individuals. Tests were conducted in three hospitals. The mean age was 43.32 years old (±17.44); mean height 167.31cm (±18.33); mean weight 70kg (±15.68). Almost 88% of the patients were in sinus rhythm. The relative frequencies of the targeted pathologies are listed in Figure 1. The collection of cardiac signals and posterior representation in virtual reality of a stereoscopic, holographic 3D-360º map, was achieved in 100% of the patients. Figure 2 shows the textile hardware with the silver dry electrodes and a screenshot of the software with an example of a voltage map in a patient in sinus rhythm. There were no adverse effects reported. The DAS is composed of 34 electrodes, being their distribution representative of the electrical activity on the torso. Several studies have discussed the minimum number of electrodes on the torso of the patient required to characterize the heart potentials from the electrical potentials on the torso surface through the inverse problem (1,2). We highlight that the representativeness condition of the electrical activity on the torso is crucial to appropriately estimate cardiac activity with the minimum number of leads on the DAS. Conclusion The use of a novel textile imageless 34-electrode device for recording ECGi for identification of electrical activity of the heart is feasible and safe.Targeted rhythmHardware and software

Sinus rhythm restoration as an independent predictor of left ventricular ejection fraction improvement in patients with the first hospitalization for heart failure and reduced ejection fraction

Abstract Background and Purpose Tachycardiomyopathy (TCM) is prevalent in heart failure with reduced ejection fraction (HFrEF). Despite its significance, a comprehensive understanding of its evolutionary trajectory and prognosis remains limited. This study aims to investigate the prognosis and left ventricular ejection fraction (LVEF) trajectory in patients with TCM compared to other etiologies within a cohort initially admitted for "de novo" HFrEF (LVEF < 40%). Methods A prospective registry was conducted across two University Hospitals, incorporating patients hospitalized with a diagnosis of HFrEF. The study encompassed 370 patients admitted between March 2021 and October 2023, with a median follow-up of 15 months (IQR 7-22). Two distinct groups were delineated based on etiology (TCM vs other etiologies). Within the TCM cohort, subgroups were established concerning LVEF improvement, following the criteria outlined in the "Universal Definition and Classification of Heart Failure" report. Categorical variables were presented as absolute frequencies and percentages, analyzed using the chi-square test. Continuous variables were expressed as mean +/- SD and compared through Student's t-test or Mann-Whitney U test. Hazard functions were estimated using the Kaplan-Meier method. Data analysis was executed using SPSS Statistics. Results In our cohort, both TCM and other etiologies groups exhibited improved LVEF post-neurohumoral blockage titration. Nonetheless, the TCM cohort demonstrated notably higher LVEF (49.1% vs. 43.5%, p = 0.005) [Figure 1]. Moreover, overall mortality, cardiovascular mortality, and the composite of CV mortality and hospitalizations for CV causes were notably lower in the TCM group compared to other etiologies [Figure 2]. Among TCM patients, those with improved LVEF during follow-up were younger (66 vs. 72), with no differences in treatment at discharge or after neurohumoral blockage titration. While achieving sinus rhythm before discharge did not correlate with LVEF improvement, attaining sinus rhythm during follow-up (at titration completion) significantly correlated with LVEF improvement [Table 1]. Multivariate analysis revealed that sinus rhythm restoration after up-titration emerged as an independent predictor of LVEF improvement, irrespective of sinus rhythm restoration at discharge or the attainment of quadruple therapy during follow-up, among other variables (Table 2). Conclusions Among patients initially admitted for "de novo" HFrEF, TCM presents a potentially more favorable clinical trajectory compared to other HF causes, showcasing reduced total and cardiovascular mortality, as well as combined cardiovascular mortality and hospitalizations for cardiovascular causes. Notably, in this patient subset, sinus rhythm restoration during follow-up emerged as an independent predictor of improved LVEF, irrespective of pre-discharge sinus rhythm restoration or adherence to comprehensive four-pillar HF management.

Silent cerebral microvascular disease and longitudinal risk of cognitive decline in atrial fibrillation

Abstract Background A relationship between silent stroke and cognitive disorder has recently been suggested in patients with nonvalvular atrial fibrillation (NVAF). This research is an exploratory research study to investigate the occurrence of asymptomatic cerebrovascular disorders with NVAF. Methods The SKAF (Silent cerebral microvascular disease and longitudinal risK of cognitive decline in Atrial Fibrillation) study is a prospective, investigator-initiated, multicenter, observational study of Japanese patients with NVAF aged 60 years or older. We had planned to enroll two hundred NVAF patients with no history of symptomatic stroke or dementia, and an anticoagulant therapy with edoxaban is being performed or an anticoagulant therapy is not being performed, and one hundred patients with sinus rhythm, for comparison. We collected patient characteristics, clinical course, the data of head MRI test and cognitive function test (Montreal Cognitive Assessment (MoCA)) at the baseline and the 24 months follow-up. The primary endpoint was the composite of silent ischemic stroke and micro-bleeding over a 24-month follow-up period. The secondary endpoint was cognitive decline over a 24-month follow-up period. Results The study was started in October 2016, with a planned 2-year recruitment period. As of January 31, 2018, a total of 326 patients were enrolled. Of those, 99 patients with sinus rhythm (SR group) and 214 patients with NVAF (NVAF group) were analyzed (male, 193 (62%) patients; age, 72.2±6.5 years). 156 of 195 (80%) patients with NVAF received the anticoagulant therapy with edoxaban. There was no significant difference of the primary composite for the endpoints between two groups (17.4% versus 17.4%; p=1.00). The incidences of silent ischemic stroke and micro-bleeding in SR and NVAF groups over a 24-month follow-up period were 9.3% and 10.8% (p= 0.833), and 8.1% and 9.2% (p=1.00), respectively. The NVAF group exhibited a significantly larger decline in cognition changes in MoCA score than SR group (-0.830 versus 0,000; p=0.0131). Notably, NVAF was found to be associated with cognitive decline. Conclusion The SKAF registry provided an equivalent risk of silent cerebral microvascular disease in patients with SR and NVAF. Clinically, NVAF had an impact on cognitive decline.

Verification of intra- and inter-atrial conduction during Bachmann's bundle pacing using longitudinal bi-atrial strain

Abstract Introduction Although atrial septal pacing has been reported to reduce atrial fibrillation (AF) burden, there is less evidence regarding its effect on the prevention of permanent AF and the improvement of long-term clinical outcomes. However, Bachmann's bundle pacing (BBp), which features P-wave morphology similar to sinus rhythm and shortened P-wave duration (PWD), was reported to significantly reduce permanent AF recurrences and occurrences compared with right atrial appendage pacing (RAAp) and non-specific right septal pacing. Purpose Possible mechanisms for AF suppression with BBp are that fast inter-atrial conduction through BB decreases global atrial activation time and the dispersion of the overall atrial refractoriness, and it prevents the decrease in left ventricular filling and increase in left atrial pressure associated with delayed left atrial contraction. Intra-and inter-atrial conduction during BBp was evaluated using longitudinal bi-atrial strain. Methods In patients with successful BBp implantation defined by electrocardiographic criteria using SelectSecure pacing lead and C315 delivery catheter (Medtronic, Inc), both left atrium (LA) and right atrium (RA) global longitudinal strain (GLS) in simultaneous phases were measured using Philips Ultrasound Workspace 2D Strain in apical 4-chamber view during atrial pacing to assess intra- and inter-atrial conduction delay. The atrial GLS were measured semi-automatically, and the strain rate was analyzed in the three segments of septal wall, lateral wall, and roof and their average. The negative peak of strain rate during atrial systole was the starting point of atrial contraction, and time to peak (TTP) was measured. The difference in TTP between septal and lateral walls in each atrium was measured as intra-atrial conduction delay and the difference in average TTP between LA and RA as inter-atrial conduction delay. Results Ten patients who underwent successful BBp were enrolled (Sick sinus syndrome: 3, advanced atrioventricular block: 2, complete atrioventricular block: 5). At implantation, bipolar atrial electrogram amplitude was 2.03±0.93 mV, atrial lead impedance was 632.7±157.6 Ω, and atrial pacing threshold was 0.7±0.2 V at 0.4 ms. The PWD during sinus rhythm on the 12-lead ECG was 132.8±10.6 ms, while during BBp it was 108.0±11.9 ms, which was significantly shorter in the BBp group (p<0.001). The intra-atrial conduction delay in RA and LA was 10.9 ± 12.1 ms and 12.1 ± 17.3 ms, respectively, and the inter-atrial conduction delay was 6.6 ± 8.6 ms. On the other hand, for the 10 RAAp and 10 sinus rhythm patients as control groups, the inter-atrial conduction delay was 29.7±13.8 ms and 8.5±9.5 ms, respectively. BBp had significantly less inter-atrial conduction delay than RAAp (p=0.005) and was comparable to sinus rhythm (p=0.719). Conclusion Longitudinal bi-atrial strain suggested that BBp significantly reduced inter-atrial delay and it might be effective in AF suppression.Longitudinal bi-atrial strain

Prevalance of incessant form of atrial fibrillation by superior vena cava (svc) firing:simplified svc and sinus node mapping(sss map) to avoid sinus node injury

Abstract Background The superior vena cava (SVC) is known as a major source of atrial fibrillation(AF), non-pulmonary vein AF foci (NPVAF). In some cases, an incessant form of AF (iAF) by SVC firing prevents obtaining the sinus node location, and anatomical SVC isolation has a risk of sinus node injury (SNI). Objective This study was aimed to explore the frequency of iAF by SVC firing and the efficacy of the simplified mapping strategy to avoid SNI. Methods Consecutive AF ablation procedures in the 3 centers were retrospectively investigated including the NPVAF prevalence. Simplified SVC/SN mapping (SSS-map: Obtaining the top-end of the SVC potential and >4points with 5-10mm spacing in the upper lateral side of the right atria (RA) for roughly locating the earliest activation site in sinus rhythm) was performed before PV isolation in the last 138 patients. In case of the initial rhythm at the procedure was atrial fibrillation, cardioversion was performed for obtaining the SSS-map. In the cases in which the high-density mapping catheters were available, the high-density activation maps of the RA in sinus rhythm were obtained to investigate the dislocation of the earliest activation site of the SSS map from the SN location. When SVC isolation was required due to iAF, SVC isolation line was designed based on the location of the top-end of the SVC potential during AF and ablative linear lesions were created to keep the distance of 5-10 mm above the second earliest activation site. Results A total of 1160 procedures in 1089 patients (male: 736[63.4%], age: 69.9, paroxysmal AF: 544[49.9%], first session: 997[85.9%]) was investigated. Prevalence of NPVAF was revealed in 160 of the all procedures (13.7%) (the SVC: 64, the posterior wall of the left atria: 24, the coronary sinus: 19, and others: 53). 16 of 160 NPVAFs (10.0%) developed to iAF by SVC firing. The SSS-map was successfully obtained in all of the last 138 patients (Initial rhythm at the procedure: AF 43.7%, Mapping time: 1.3±0.6 min, number of obtained points: 8.4±1.3). In 21 patients in which the high-density RA map was obtained, the SN dislocation distance was 5.1±2.2mm between the SSS map and the high-density RA map. Five of 138 developed to iAF by SVC firing, and SVC isolation based on the SSS-map was successfully achieved without SNI in the cases. Conclusion This study indicated iAF driven by SVC firing after PV isolation occurred in certain number of patients. The SSS-map before PV isolation was practical and showed the potential to be the mapping strategy avoid the SN injury in such cases.

Validation of diagnostic wearable ECG data from high-risk patients and integration into the atrial fibrillation catheter ablation pathway

Abstract Background Wearables like the Apple Watch (AW) offer non-invasive, long-term monitoring and patient-led, single-lead ECG recordings. Although validated for Atrial Fibrillation (AF) detection in the general population, the accuracy and clinical utility of the single-lead ECG recording feature for the diagnosis of AF has not been evaluated in patients at high risk of atrial arrhythmias.(1) An evaluation of the accuracy of the Wearable-derived labels is important to determine the feasibility of integrating AW-based remote monitoring into clinical pathways. Objective To evaluate the accuracy and data burden from AW-based, patient-led ECG monitoring in patients undergoing AF catheter ablation. Methods Patients referred for first-time AF catheter ablation to the Study Institution between January 2022 and March 2023 were invited to enrol in the AF Follow-up with Apple Watch (AFFU-AW) Trial. Patients randomised to the active arm of the study received 12 months of post-ablation follow-up using a loaned Apple Watch. Participants underwent an education session and were asked to perform daily ECGs; sending through any labelled as AF, inconclusive, or in the context of symptoms. The accuracy of the automated ECG labelling was determined against blinded, independent labelling by two experienced Electrophysiologists. Results 1093 remote transmissions were emailed in for evaluation from 52 patients to the Study team. This was a median of 6 [2, 17] per patient and a receiver burden of 2 [1, 4] ECGs per day. 475 were categorised by the AW as AF with a sensitivity of 0.71 and specificity of 0.96 compared to expert labelling. 342 (31%) were not categorised by the wearable, with an ‘inconclusive’ interpretation (161 [47%]) or ‘high heart rate’ (108 [32%]) as the most cited reasons. 178 (55%) of the uncategorised ECGs were subsequently overread as AF. Accompanying symptoms were reported with 324 (30%) ECGs, most commonly palpitations. Conclusion This is the first reported evaluation of the AF diagnostic feature based on AW ECG recordings as part of a remote patient rhythm surveillance pathway after catheter ablation. The high positive predictive value of ‘Sinus Rhythm’ and ‘AF’ labels and the high specificity of the ‘AF’ label are comparable to diagnostic algorithms in implantable loop recorders.(2) The source code to automate data curation and structured databasing of wearable ECGs has been made available for care providers to integrate the service into device monitoring workflows.(3)

The occurrence of atrioventricular nodal reentrant tachycardia requires not only the electrophysiological substrate but also the electro-anatomical characteristics in the triangle of Koch

Abstract Background Some patients do not develop atrioventricular nodal reentrant tachycardia (AVNRT) clinically despite having the electrophysiological substrate for AVNRT; however, the cause remains unclear. Recently, the conduction to the slow pathway has been reported to be visualized using high-density mapping in the triangle of Koch (ToK) during sinus rhythm. Purpose To investigate whether the conduction to the slow pathway is associated with the occurrence of AVNRT. Methods We studied 83 patients (55 males, 67 ± 13 years, 10 with typical AVNRT, 66 atrial fibrillation; AF, 5 atrioventricular reentrant tachycardia; AVRT, and 2 Atrial Flitter) who received electrophysiological test and high-density mapping in the ToK during sinus rhythm. The conduction pattern to the slow pathway, rotating around the end (pivot point: PP) of the functional block line (FBL), was evaluated using the Advisor HD Grid mapping catheter. Results 10 out of 10 AVNRT (100%), 17 of 66 AF (26%), and 1 of 4 AVRT showed PP and FBL (p<0.0001). 21 out of 21 (10 AVNRT and 11 AF) with the jump-up phenomenon in atrioventricular conduction indicated PP and FBL (100%), meanwhile 7 of 62 without jump-up phenomenon showed PP and FBL (11%) (p<0.0001). Among patients (10 AVNRT and 9 AF) who had the electrophysiological substrate for AVNRT (jump-up phenomenon and retrograde ventriculoarterial conduction), patients with AVNRT had a longer distance from PP to the tricuspid annulus; TA (16.9mm vs, 13.4mm, p=0.0116) than patients with non-AVNRT. There were no differences in the length of FBI, distance and conduction time from His to PP, distance and conduction time from PP to CS ostial, and the area size of ToK. All AVNRT patients underwent linear ablation from PP to TA and showed loss of atrial potential in the region between PP, TA, and His, AVNRT was no longer provoked, and in 8 out of 10 patients, a jump-up phenomenon disappeared. Conclusion Patients with AVNRT showed a functional block line and a longer distance from the pivot point to the tricuspid annulus. The occurrence of AVNRT requires not only the electrophysiological substrate but also the electro-anatomical characteristics, especially in the triangle of Koch.

Impact of changes in left heart geometry on predicting new-onset atrial fibrillation in patients with hypertension

Abstract Background Hypertension-induced left ventricular hypertrophy (LVH) increases end-diastolic LV pressure and contributes to left atrial enlargement (LAE), which are associated with development of atrial fibrillation (AF). However, the impact of LVH and LAE and their regression following antihypertensive therapy on AF incidence remains unclear. Purpose This study aimed to investigate the impact of changes in the LVH and LAE status on the occurrence of new-onset AF (NOAF). Methods This retrospective analysis included patients with sinus rhythm who underwent echocardiography at hypertension diagnosis and after 6–18 months. LVH was defined as LV mass index >115 g/m2 (men) and >95 g/m2 (women), and LAE was defined as LA volume index >42 ml/m2. LVH and LAE regression was defined as the absence of LVH and LAE on follow-up echocardiography, respectively. The occurrence of NOAF was assessed in relation to changes in LVH and LAE status. Results Among the 1,464 patients included in the study, 163 (11.1%) patients developed NOAF during a median follow-up of 63.8 months (interquartile range, 35.9–128.5 months). On average, 12 electrocardiograms per patient were reviewed for AF detection. New-onset LVH (adjusted HR 1.88, 95% CI 1.20–2.94, P=0.006) and LAE (adjusted HR 1.89, 95% CI 1.05–3.40, P=0.034) were significant predictors of NOAF. Conversely, regression of LVH (adjusted HR 0.51, 95% CI 0.280.91, P=0.022) or LAE (adjusted HR: 0.30, 95% CI 0.15–0.63, P=0.001) after antihypertensive therapy was associated with a reduced risk of NOAF. The risk of NOAF was higher in patients with LVH and LAE together (adjusted HR 4.30, 95% CI 2.81–6.56, P<0.001) than in those with either LVH or LAE, or those with neither, as determined by follow-up echocardiography. Conclusion In patients with hypertension and sinus rhythm, regression of LVH and LAE following antihypertensive therapy is associated with a decreased incidence of NOAF, whereas newly developed LVH or LAE is associated with a higher risk of NOAF. The changes in left heart geometry can serve as a predictive marker for NOAF in patients with hypertension.

Novel approach of slow pathway ablation in common atrioventricular nodal reentrant tachycardia by peak frequency map

Abstract Background It is difficult to visualize slow pathway in atrioventricular nodal reentrant tachycardia (AVNRT) even with recent high-density mapping. This could be because the slow pathway potential is buried by the potential of atrial working cells during sinus rhythm and tachycardia. In other words, it is extremely difficult for conventional 3D mapping systems to annotate slow pathway potential even though the histological run of slow pathway is known .[1], [2] Purpose The purpose of this study is to visualize the atrial myocardial junction of rightward inferior extension by the peak frequency map of Ensite X in common AVNRT and to evaluate whether relative high frequency (HF) sites in low voltage area extending from Koch's triangle to tricuspid annulus (TA) is effective targets of slow pathway ablation and the characteristics of junctional rhythm (JR) after radiofrequency application. Methods This study is single-center prospective cohort study. In 37 consecutive common AVNRT patients, novel approach and conventional approach of slow pathway ablation were performed in 17 and 20 patients, respectively. The conventional approach is anatomical and electrophysiological approach. Peak frequency map was performed during sinus rhythm with HD-grid catheter in novel approach patients. A frequency scanning is performed to locate relative HF sites on the tricuspid annulus. Radiofrequencey application is 30 W, 30-60 sec, and the end point was no inducibility or until one echo under load of isoproterenol. Results The success rate was 100 % with two approaches. The relative HF sites in low voltage area were distributed at the TA side from 4 to 5 o'clock in all novel approach patients, mean peak frequency in success site was 419 ± 87 Hz. The distance to His bundle from success site was farther (24.8 ± 4.9 vs. 12.8 ± 4.4 mm, p<0.001), JR was slower (93 ± 14 vs. 118 ± 10 bpm, p=0.013), time to JR occurrence was shorter (3.0 ± 1.3 vs. 7.6 ± 4.6 sec, p=0.003), and elimination rate of jump up (78 % vs. 40 %, p=0.06) was higher in novel approach. Conclusions The relative HF sites in low voltage area at TA side from 4 to 5 o'clock by peak frequency map could be novel target of slow pathway ablation with high success rate and sufficient safety and efficiency.peak frequency map

Comparison of left atrial and left atrial appendage mechanics in patients with ischaemic strokes of different aetiologies

Abstract Background Left atrial (LA) and left atrial appendage (LAA) mechanical dysfunction account for an increase in cardioembolic stroke risk in atrial fibrillation (AF), and more recently in individuals in sinus rhythm (SR). However, the exact contribution of LA and LAA to the pathogenesis of thromboembolic events is not fully understood. Here, we aimed to assess the alterations of LA and LAA mechanics in different stroke subtypes. Methods We recruited three groups of participants: patients with paroxysmal or persistent AF with a history of stroke (AF-stroke, n=69,respectively), individuals in SR with no history of AF but with acute ischaemic stroke(non-AF stroke,n=46); individuals with no history of AF or stroke(control group,n=17). Patients with AF were further categorized into sinus rhythm group (AF-stroke-SR,n=24) and AF rhythm group(AF-stroke-AF, n=45) according to the rhythm at the time of echocardiography. Using speckle-tracking echocardiography, global longitudinal strain (GLS) and mechanical dispersion (MD) of LA and LAA were measured in all patients. Mechanical dispersion was defined as the standard deviation of the time to peak of the regional strain corrected by R-R interval. Results Patients with AF-stroke demonstrated prominently impaired LA and LAA mechanics(LA GLS: 20±6%(AF-stroke-SR),11±4%(AF-stroke-AF); LA MD: 9±3%,11±3%; LAA GLS: 15±3%,11±4% ; LAA MD: 11±4%,12±3% ,respectively) compare with those with non-AF stroke and controls (LA GLS:35±8%, 41±11%;LA MD,6±2%, 4±2%; LAA GLS:21±5%, 23±7%; LAA MD:8±4%, 7±3%,respectively) (all p<0.01). Interestingly, LA and LAA mechanical function was not significantly different between patients with non-AF strokes and the control group. In multivariable analysis, only AF-strokes were independently associated with LA and LAA GLS after adjusting for age and comorbidities (both P<0.01). Conclusions Mechanical dysfunction of LA and LAA might play a greater role in pathogenesis of strokes related to AF rather than non-AF strokes.

Prognostic value of left atrial and ventricular strain in moderate atrial and ventricular secondary mitral regurgitation

Abstract Background Secondary mitral regurgitation (SMR) is associated with increased morbidity and mortality. In these patients, left ventricular global longitudinal strain (LVGLS) and left atrial reservoir strain (LARS) have been proposed to improve risk stratification. However their prognostic value was shown to be inconsistent when considering the SMR etiology (i.e. atrial or ventricular), possibly due to be the influence of atrial fibrillation (AF) on these measures and specifically LARS. Moreover, data focusing on moderate SMR is lacking. Aim To investigate the prognostic value of LVGLS and LARS in patients with SMR stratified according to etiology, and to identify optimal threshold for both measures. Methods Patients (n=1061; age 68±11years , 59% male) with moderate SMR were retrospectively included and classified as ASMR or VSMR, and further subdivided into "sinus rhythm (SR) subgroup" (ASMR-SR: n=68 , VSMR-SR: n=435) or as "AF subgroup" (ASMR-AF: n=284 , VSMR-AF: n=274), if patients had history of AF. The endpoint was a composite of heart failure events and all-cause mortality. Threshold values for LVGLS and LARS were defined based on spline curve analysis. Results As compared to VSMR, ASMR patients were more frequently female (61% vs. 35%, p<0.001), had less comorbidities and were less symptomatic (i.e. NYHA functional class III-IV in 11% of ASMR vs. 24% of VSMR, p<0.001). For the echocardiographic characteristics, VSMR patients showed lower LV ejection fraction and LVGLS, as compared to ASMR patients. For both ASMR and VSMR, patients in the AF subgroups had larger LA volume index, lower LARS and more severe tricuspid regurgitation (Figure 1). During a median follow-up of 78 (IQR: 44-111) months, 27% of ASMR-SR, 37% of ASMR-AF, 50% of VSMR-SR and 72% of VSMR-AF group reached the combined endpoint. Separated multivariable cox regression analyses were performed in ASMR and VSMR patients (Table 1): for both etiologies, LARS and LVGLS were independently associated with the endpoint after correcting for other significant variables at the univariate analysis, including the SR or AF group and the interventions during follow-up. In addition, a stepwise addition of LVGLS and LARS to a basic model led to a significant difference in the likelihood ratio for both groups. The thresholds of LVGLS and LARS associated with an increased risk of the combined endpoint differed per etiology. For LVGLS the threshold was <16% for ASMR, and <12% for VSMR. When considering LARS assessment, different thresholds were identified according to the SR or AF group: <18% in ASMR-SR; <15% in ASMR-AF; <17% in VFMR-SR and <12% in VFMR-AF. Conclusion In moderate SMR patients, LVGLS and LARS are independently associated with outcomes both in ASMR and VSMR and could be considered to improve risk stratification. However, lower threshold for both parameters should be considered based on etiology and on the presence of AF.