History Of Atrial Fibrillation Research Articles

Anticoagulation for Patients with Atrial Fibrillation Receiving Dialysis: A Pilot Randomized Controlled Trial.

Atrial fibrillation is common in individuals receiving dialysis. The role of oral anticoagulation in this population is uncertain given its exclusion from previous seminal clinical trials. Our objective was to determine the feasibility of performing a large definitive trial to establish the optimal anticoagulation strategy in individuals with atrial fibrillation receiving dialysis. The SAFE-D trial was a parallel-group, open-label, allocation-concealed, pilot randomized control trial that took place at 28 centres in Canada and Australia. The trial included adults (≥18 y) undergoing dialysis with a history of non-valvular atrial fibrillation who met the CHADS-65 criteria. Participants were randomized 1:1:1 to receive dose-adjusted warfarin, apixaban 5 mg twice daily, or no oral anticoagulation and followed for 26 weeks. The primary outcomes evaluated the following measures of feasibility: a) recruitment of the target population within 2 years from the start of the trial; and b) adherence of >80% of randomized patients to the allocated treatment strategy at the conclusion of follow-up. Secondary outcomes included stroke and bleeding. From December 2019 through June 2022, 151 patients were enrolled and randomized to apixaban (n =51), warfarin (n=52) or no oral anticoagulation (n=48). Allowing for pauses related to the COVID pandemic, recruitment was completed in 30 months, and 123 (83%) of participants completed follow-up in their allocated treatment arm. There was one adjudicated stroke event. Eight participants had a major bleeding event (4 warfarin, 2 apixaban, 2 no oral anticoagulation). Death occurred in 15 participants (9 warfarin, 2 apixaban, 4 no oral anticoagulation). Time in the therapeutic range for warfarin recipients was 58% (IQR 47%-70%). We have demonstrated the feasibility of recruitment and adherence in a trial that compared different anticoagulation strategies in patients with atrial fibrillation receiving dialysis.

Left atrial strain differences between hypertensive and sarcomeric left ventricular hypertrophy: a sign of sarcomeric auricular myopathy?

Abstract Introduction In clinical practice, left ventricular (LV) hypertrophy is a common finding that can be caused by physiologic or pathologic conditions. An etiologic diagnosis is extremely important because it may change the prognosis and management of the patient and his family. Left atrial (LA) dysfunction is common due to diastolic dysfunction but, in patients with sarcomeric LV hypertrophy, primary cardiomyopathy disease could also be present. Purpose To evaluate if there are differences in LA function between arterial hypertension (HT) and hypertrophic cardiomyopathy (HCM) patients. Methods 73 patients with HCM (according to ESC guidelines criteria) and 82 patients with HT (under treatment with ≥1 hypertensive drug for ≥3 months) and ≥13mm of LV hypertrophy underwent an echocardiography to assess LA function with strain analysis and LV diastolic function. Continuous normally distributed variables were compared with T-student test and categoric variables with square-chi or exact Fisher test if required, accepting as significant a p-value <0.05. Results Globally, HCM patients showed thicker LV walls and larger LA indexed volumes (18.7±4.7 vs. 13.3±0,8 mm and 44.9±20.7 vs. 30.7±8.8 ml/m2, p<0.000 for both). Also, HCM patients presented diastolic dysfunction and atrial fibrillation history in a higher frequency (31 vs. 7.6% and 16.4% vs. 0%, p<0.000 for both). LA strain was significantly lower in HCM patients as compared to the HT group (LA contractile 11.5±5.8 vs. 17.2±4.4, p<0.000; LA conduit 12.2±5.4 vs. 13.3±3.8, p=0.041; and LA reservoir 23.9±8.7 vs. 31.1±5.9, p<0.000). In the subgroup of patients with moderate-severe LV hypertrophy (<17mm) and no significant mitral regurgitation (n=103; HCM=21, HT=82), LA contractile strain remained lower in HCM as compared to HT patients (13.2±4.8% vs. 17.2±4.4%, p<0.000) (figure 1); without differences in diastolic dysfunction, LA volumes, significant mitral regurgitation or atrial fibrillation history. Conclusions Our results show that LA strain is more impaired in HCM patients as compared to HT patients. Specifically, contractile LA strain remained lower even in those patients with moderate-severe LV hypertrophy, despite having similar LV diastolic function, LA indexed volumes, significant mitral regurgitation, or atrial fibrillation history. These findings could be caused by HCM involvement of the LA myocytes. In the context of moderate-severe hypertrophy of unknown origin with non-significant mitral regurgitation, the detection of abnormally reduced LA strain could indicate the presence of an HCM.Figure 1

Safety of left atrial appendage amputation during cardiothoracic surgery

Abstract Background Patients with atrial fibrillation (AF) are at risk for ischemic strokes, often originating from the left atrial appendage (LAA). Preventive LAA amputation (LAAA) during cardiac surgery has been shown to reduce ischemic stroke risk, both in patients with and without AF. However, the short-term safety and functional implication of LAAA in non-AF patients remain poorly understood. Besides possible surgical complications, there are suggestions that LAAA could lead to postoperative AF or influence neurohumoral changes resulting in fluid overload. Purpose To evaluate the safety of LAAA in patients without a history of AF undergoing routine cardiac surgery. Methods Patients underwent elective cardiac surgery between May 5 2015 and April 18 2018 in two high volume centers. Main inclusion criteria were a CHA2DS2-VASc≥ 2 and no history of AF. Patients without a history of AF, that participated in the PREDICT-AF study underwent concomitant LAAA and were compared with patients undergoing cardiothoracic surgery who were approached for participation in PREDICT-AF, but declined and subsequently did not undergo LAAA. Informed consent for the retrospective use of data was obtained through an opt-out procedure in these patients. The primary outcome of this analysis was the number of patients with any serious adverse event within 30 days postoperatively. Secondary outcomes were AF within 30 days postoperatively, death, rethoracotomy, time on extra corporal circulation(ECC) and heart failure related symptoms assessed through congestion on x-chest and weight trends. Adverse events were independently adjudicated by a cardiothoracic surgeon using pre-specified definitions. Results 150 patients in PREDICT-AF underwent LAAA. 284 Eligible patients declined participation and formed the control group. Patients in the LAAA group were more frequently male (87.3% vs 72.5%; p=0.001), were taller (176.0cm ± 8.2 vs 172.6cm ± 9.9; p<0.001) and weighed more (86.1kg CI[80.0, 92.2] vs 81.6kg CI[71.9, 91.1]; p=0.001) compared to controls. There were no significant differences in occurrences of serious adverse events (8% vs 12%; p=0.265), deaths (1.3% vs 1.8%; p=1) or rethoracotomies (3.3% vs 1.8%; p=0.483) between the LAAA and control group. Also, there was no difference in the incidence of postoperative AF (57, 38% vs 90, 31.7%; p=0.225), ECC time (104.5 minutes CI[81.0, 129.0] vs 98.0 CI[80.0, 124.5] p=0.371) or the presence of chest x-ray congestion (26.0% vs 27.8%; p=0.771) between the groups (Figure 1A). The spline plot of perioperative weight change from baseline, reveals no notable differences between the two groups (Figure 1B). Conclusion LAAA during routine cardiothoracic surgery is not associated with more surgical complications, postoperative atrial fibrillation or heart failure related symptoms. Given the generally high AF risk in patients undergoing cardiothoracic surgery, a strategy to preemptively resect the LAA may be feasible and safe.Figure 1 A & B

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.

Proteomic biomarkers and biological mechanisms associated with atrial fibrillation in heart failure patients

Abstract Background Atrial fibrillation (AF) and heart failure (HF) are intertwined conditions with high mortality rates and large impact on quality of life, and their coexistence is increasingly prevalent. Both conditions influence each other’s development and progression, and share many risk-factors—such as hypertension, obesity, diabetes mellitus and ischaemic heart disease. Moreover, their combined presence further increases the risk of hospitalization and mortality. The biological mechanisms at play in HF patients with AF may therefore differ from those in HF patients without AF. Purpose We aimed to describe the differences in pathophysiological pathways in HF patients with versus without AF, by identifying biomarkers associated with AF from a panel of 4210 circulating proteins and subsequently examining biological mechanisms related to these biomarkers. Methods We examined 377 ambulant HF patients with reduced ejection fraction from a longitudinal cohort study. We measured 4210 circulating proteins in baseline blood samples using an aptamer-based multiplex proteomic approach. Associations between AF (known AF history or AF on the baseline ECG) and the proteins were assessed using linear regression models adjusted for age, sex, kidney function and duration of HF at baseline. Associations of proteins significantly related to AF, with biological processes, were assessed using network-based clustering and subsequent enrichment analysis. Results The median [25th, 75th percentile] age was 64 [55, 72], 73% [274/377] were male, 28% [104/375] had NYHA-class III or IV, and 37% [139/377] had AF (either AF history: 36% [137/377] or AF on baseline ECG: 8% [30/374]). We found 71 proteins significantly associated with AF (FDR<0.05), including well-studied (e.g. troponin T, IGFBP7, MFAP4, BMP10, angiopoietin 2) and lesser studied (e.g. olfactomedin−like protein 3, keratocan, basigin) proteins in the AF domain. Our pathway analysis revealed clusters of proteins related to various underlying mechanisms, such as axon guidance, elastic fibre assembly, macrophage derived foam cell differentiation, ether lipid metabolism and amyloid-beta binding. Overviews of the significantly associated proteins and related biological mechanisms are provided in Figures 1 and 2. Conclusion HF patients with AF have distinct proteomic profiles and these differences are related to various biological mechanisms, many of which can be associated with atrial remodelling. This study provides an overview of the biological mechanisms behind AF in HF, confirms prior findings regarding AF-related proteins, and could guide future research in novel treatment targets and HF-AF management.Figure 1:Proteins associated with AFFigure 2:Biological mechanisms

Severe aortic stenosis is associated with left atrial prothrombotic flow changes that persists despite successful aortic valve replacement

Abstract Background Severe aortic stenosis (AS) is associated with ischaemic stroke independently of atrial fibrillation (AF) or other causes. Even after aortic valve replacement (AVR), patients remain affected by up to 15% five-year rate of incident ischaemic strokes independently of AVR-related complications and with knowledge gaps in the underlying pathophysiology. Purpose To assess whether severe AS leads to prothrombotic left atrial (LA) flow changes with reduction of LA velocities and vorticity which do not normalise after AVR. Methods Seventy-seven participants without history of AF were recruited in this study: N=40 with severe AS (60% male; age 73 ±10 years, BMI 28 ±5 Kg/m2, median CHA2DS2VASc = 3) and N=37 controls with similar clinical risk profile (51% male; age 71 ±6 years, BMI 28 ±5 Kg/m2, median CHA2DS2VASc = 3). All participants underwent a cardiovascular magnetic resonance (CMR) scan to quantify left ventricular (LV) volumes, mass, and ejection fraction (LVEF), LV global longitudinal strain (GLS) as a sensitive marker of longitudinal dysfunction, LA maximum volume and emptying fraction (LAEF), LA blood flow peak velocity and vorticity by 4-dimensional flow CMR. Out of the 40 patients with severe AS, N=23 (58%) underwent a successful AVR and were followed-up with a repeat CMR scan at approximately 6 months after surgery. Results When compared to matched controls, patients with severe AS displayed significantly higher LV mass, smaller LA and LV volumes (i.e. concentric LV hypertrophy), significantly reduced GLS but higher (more hyperdynamic) LVEF (all p<0.05), as expected. LAEF (i.e. global LA function) was not significantly different from controls but despite this, severe AS was associated with slightly lower LA peak flow velocity (mean 0.25 vs. 0.28 m/sec respectively) and lower LA flow vorticity (mean 16.6 vs. 21.1 radians) compared to controls (both p<0.05). Successful AVR led to complete regression of LV hypertrophy (p<0.05) with LV mass that was no longer different from controls (p>0.05). Nevertheless, post-AVR patients displayed a persistent adverse morpho-functional phenotype characterised by persistently smaller LA and LV volumes, persistently hyperdynamic LV function with reduced GLS (all p<0.05), as well as adverse LA flow changes with significantly lower velocity (mean 0.24 vs 0.28 m/sec, p=0.003) and vorticity when compared to controls (17.1 vs 21.1 radians, p<0.001). Conclusions Patients with severe AS display adverse LA physiology and structure (prothrombotic LA flow characteristics in smaller LA size) and LV changes (smaller size with reduced longitudinal function and hyperdynamic function), which persist after successful AVR despite normalisation of the LV hypertrophy.Figure 1

Pathogenic cardiomyopathy gene variants inform prognosis in atrial fibrillation: results from exome sequencing in over 17,000 patients in TIMI trials

Abstract Background Rare genetic variants in cardiomyopathy genes are associated with risk of atrial fibrillation (AF), even in the absence of overt ventricular dysfunction. Data on clinical outcomes for rare genetic variant carriers among patients with AF remain sparse. Purpose We aimed to study the prognostic implication of rare pathogenic/likely pathogenic (PLP) variants for dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC) in patients with AF from large, well-phenotyped randomized clinical trials. Methods and results Rare variants were called using exome sequencing data in 5 large clinical trials from the TIMI study group (ENGAGE-AF, FOURIER, SAVOR, PEGASUS, DECLARE). PLP variants for cardiomyopathy were identified using phenotype- and gene-specific curation of protein-truncating variants and high-confidence variant classifications from the ClinVar database. In 17,190 patients with a history of AF, we identified 421 (2.4%) PLP variant carriers (age 67±10, 35% women) and 16,769 (97.6%) pts without PLP variants (age 70±9, 36% women). Among these individuals, we identified 265 DCM carriers (1.5%), 106 (0.6%) HCM carriers and 54 (0.3%) ARVC carriers. In this cohort, 9,275 (54%) had a history of heart failure (HF) and 2,991 (17.4%) prior ischemic stroke. Over 2.5 years median follow-up, 1,365 pts (7.9%) were hospitalized for HF, 599 (3.5%) had an ischemic stroke, and 1147 (6.7%) died of cardiovascular causes. In logistic regression analyses adjusting for age, sex, trial, and principal components of ancestry, PLP variants were significantly associated with a history of HF (OR 1.66, p<0.0001), most notably for DCM variants (OR 1.97, 1.48-2.62, p<0.0001). PLP variants were independently associated with incident HF admissions (adj HR 1.75, 1.39-2.29, p<0.0001), most notably for HCM (adj HR 2.59, 1.68-3.99, p<0.0001) and ARVC variants (adj HR 2.50, 1.34-4.66, p=0.004). The increased risk of HF admissions remained consistent in patients with (adj HR 1.49, 1.11-2.00, p=0.009) and those without (adj HR 1.88, 1.00-3.54, p=0.049) a history of HF. PLP variants were also associated with higher risk of cardiovascular death (adj HR 1.46, 1.06-2.02, p=0.02), most notably for DCM variants (adj HR 1.77, 1.21-2.58, p=0.003). In contrast, PLP variants were not associated with history of ischemic stroke at baseline (adj OR 0.99, p=0.96) nor with incident ischemic stroke (adj HR 0.95, p=0.84). Conclusion In patients with AF, rare cardiomyopathy gene variants are associated with increased risks of HF and of cardiovascular death, but not stroke. These results, collected from large well-phenotyped randomized clinical trials, demonstrate an important prognostic implication for rare genetic variants for CMP in pts with AF.

Temporal and age-related trends in risk factors for development of atrial fibrillation in peripartum patients

Abstract Background Incidence of atrial fibrillation (AF) in pregnancy has steadily increased over the past two decades and may be related to changes in rates of AF risk factors. Objective To characterize trends in the prevalence of AF risk factors among patients with peripartum AF. Methods TrinetX, a large national healthcare database, was used to identify patients with peripartum AF from 2017-2022. Inclusion criteria were female patients aged >18 years old who received a diagnosis of AF within one month prior to and one year after a diagnosis of pregnancy. Annual prevalence of pre-existing AF risk factors, including diabetes, chronic kidney disease (CKD), obesity, and hypertension, were obtained, normalized to the annual number of peripartum AF cases, and followed. In a second analysis, student’s t-test and standardized mean difference were used to compare the rates of AF risk factors between patients with peripartum AF and pregnant patients with no history of AF within the same time frame. Comparisons were performed across age ranges. Results From 2017-2022, there were 6,465 patients with peripartum AF and 2,852,348 pregnant patients with no AF. There was an increase in the proportion of peripartum AF patients with pre-existing obesity (16.7% to 18.5%) and hypertension (28.9% to 33.7%). In comparing pregnant patients with no AF history with peripartum AF patients, the standardized mean difference for rates of all risk factors increased with age group. The peripartum AF group had significantly higher rates of all risk factors across all age groups (p < 0.0001 for all groups). Conclusion Rates of pre-existing obesity and hypertension increased among patients with peripartum AF, which could be a factor in increasing rates of peripartum AF. Differences in rates of AF risk factors between peripartum AF patients and pregnant patients with no AF were more pronounced at older age groups.

Left atrial strain parameters are able to predict presence of atrial fibrillation

Abstract Background Three-dimensional speckle-tracking echocardiography allows evaluation of left atrial function, left atrial function has been assessed in various diseases for prognostication [1]. Atrial fibrillation (AF) is most common arrhythmia, and one of its manifestations is increased left atrial filling pressure and left atrial dilatation. Methods Echocardiography loops were collected between December 2019 and December 2021, only valid atrial loops, and sinus rhythm during examination. Spearman test was used for correlation matrices of left atrial parameters; uni- , multivariate and binary logistic regression to predict presence or absence of atrial fibrillation. Results A total of 116 patients (50% females) aged 76.9±11.2 were included in the analysis. Males and females differed in anthropometric and other clinical parameters. Intra- and interobserver variability was close to 1% since most of the measurements are semi-automatized. 2D and 3D left atrial volumes correlated significantly (r=0.8, P<0.0001, Fig.1). Almost all left atrial strain measurement uni- and multivariately predicted the presence of atrial fibrillation, binary logistic regression identified two most significant parameters (left atrial longitudinal strain reservoir and conduit phase, LASr, LAScd, P=0.042, P=0.044, respectively, Fig.2). LASr is significantly greater in patients without history of AF vs patient with AF history, (16±16, 10.5±7.1, respectively, P=0.012). The probability of sinus rhythm increases linearly with the increasing value of LASr. Conclusion Left atrial longitudinal strain was able to differentiate patients with paroxysmal atrial fibrillation as compared to patients without history of this arrhythmia.

Performance of apple watch for detecting atrial fibrillation among a known atrial fibrillation population

Abstract Background Photoplethysmography (PPG) based consumer accessible devices with algorithms for irregular rhythm detection are gaining popularity as an opportunistic screening tool for atrial arrhythmias, and are FDA cleared for use in patients without a history of atrial fibrillation (AF). However, these devices are increasingly used for the management of AF, a purpose for which some algorithms are not intended. Purpose To compare the performance of the Apple Watch Irregular Rhythm Notification (IRN) with an implantable cardiac monitor (ICM) for the detection of atrial fibrillation (AF) in patients with known AF from the DEFINE AFib study. Methods Patients with known AF, a LINQ or LINQ II ICM, and an Apple Watch with PPG-based IRN activated were included in the analysis. ICM detected AF episodes served as the standard to which Apple Watch IRNs were compared. All AF episodes detected by the ICM device were manually adjudicated by two trained, independent reviewers with a third independent reviewer in situations of disagreement. Only AF episodes ≥60 minutes during a 75-minute window in which the Apple Watch was monitoring were included in accordance with the known Apple Watch algorithm detection parameters. To eliminate oversampling of ICM detected episodes compared to Apple Watch IRNs, 1,000 simulations of one randomly selected episode per subject was done to avoid single-subject bias. Results In total, 97 subjects were analyzed of which 42 had an AF episode ≥60 minutes. Applying the 75-minute window of Apple Watch monitoring to episodes ≥60 minutes, 20 subjects had qualifying, adjudicated ICM detected AF. These 20 subjects accounted for 481 qualifying AF episodes. Of the ICM detected episodes, 191 (40%) occurred while an Apple Watch was not being worn. In total, 11/20 (55%) subjects had an IRN generated by the Apple Watch. Adjudication of the ICM episodes resulted in 290 true positive AF episodes ≥60 minutes during a 75-minute window while the watch was actively monitoring, with 74 (26%) of those episodes triggering an IRN resulting in a per episode sensitivity of 24 ± 7% and PPV of 91 ± 4% (Figure 1A). The efficacy of Apple Watch to detect AF episodes of differing lengths was assessed for episodes between 1-6 hours, 6-12 hours, 12-24 hours, and > 24 hours with sensitivities of 19 ± 19%, 38 ± 8%, 32 ± 10%, and 31 ± 8%, respectively (Figure 1B). The Apple Watch generated an annualized false positive rate of 2.25 IRNs for every patient year of monitoring. At the subject level, Apple Watch had a sensitivity of 48%, specificity of 100%, PPV of 100%, and NPV of 71% (Figure 1A). Conclusions In patients with a history of AF, the Apple Watch IRN was most sensitive at the individual subject level while watch performance was lower by episode. The current IRN algorithm favors longer episode durations. The limited sensitivity, dependence on user wear-time, and reliance on long-durations of AF limit the use of Apple Watch for AF management.

Left atrial function for predicting atrial fibrillation: a machine learning approach

Abstract Background Common risk scores for atrial fibrillation (AF) are based on clinical risk factors, and little is known about the contribution of left atrial (LA) function parameters to risk assessment. Purpose To determine whether a machine learning-based model that includes LA function parameters outperforms a commonly used risk scores, the CHARGE-AF, in predicting AF. Methods Participants in the Atherosclerosis Risk in Communities (ARIC) Study (a community-based cohort study in the USA) who attended visit 5 (2011-2013) and without a history of AF were included in this analysis. Incident AF was ascertained from ECG during study visits, hospitalization discharge codes, and death certificates. Random survival forest methodology was used to build a prediction model for AF; candidate variables included traditional clinical risk factors and measures of LA structure and function. Dataset was randomly split into a training (75%) and testing (25%) cohort. For each variable, importance was measured based on the reduction in Harrell’s c-statistic if the variable was randomly permuted prior to obtaining predicted values. Variables significantly associated with AF were included in the final model. Model calibration was tested using the Greenwood-Nam-D'Agostino (GND) test. Discrimination ability of our model was assessed in the testing cohort using Harrell’s c-statistic and compared with that of the CHARGE-AF model. Results 4,909 participants (59% female, 22% Black, mean age 75 years) were included. During a median follow-up of 7.0 years (1st-3rd quartile: 5.4-7.8), 650 participants developed AF. Variables significantly associated with incident AF were race, triglycerides, systolic blood pressure, coronary heart disease, age, LA maximal volume index, NT-proBNP, and LA reservoir strain (Figure 1). LA reservoir strain was the variable most strongly associated with AF. The final model showed good discrimination (c-statistic (95% CI): 0.734 (0.698-0.768)). The GND test did not detect statistically significant miscalibration (GND p=0.08). Compared with our model, CHARGE-AF had lower discrimination ability (c-statistic (95% CI): 0.635 (0.594-0.677)) and the difference was statistically significant (difference in c-statistic (95% CI): 0.099 (0.043-0.152)). Conclusion A machine learning-based model with few variables including LA function outperforms a commonly used risk model in predicting AF. Incorporation of LA functional assessment may help inform clinicians regarding individual risk of AF.

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.

A cohort study examining predictors of stroke and bleeding among people with congenital heart disease and atrial fibrillation

Abstract Background Congenital Heart Disease (CHD) is associated with development of atrial fibrillation (AF) at an early age. With increased survival of this cohort into adulthood, the prevalence of concurrent CHD and AF is expected to increase over the next several decades. Little is known about the utility of clinical risk factors or prediction models in determining bleeding or stroke rates in adults with CHD and AF. Purpose This study aims to measure the performance of the CHADSVASC and HASBLED scores in a cohort of people with CHD. The association between traditional stroke and bleeding risk factors, as well as CHD-specific factors, will be quantified. Methods Patients age 18 or older attending one of three centers in the USA were included in this study if they had a history of AF on ECG, holter monitor or device interrogation, in addition to a diagnosis of Tetralogy of Fallot (TOF), Double Outlet Right Ventricle (DORV), or Pulmonary Atresia with Intact Ventricular Septum (PA-IVS). Outcomes were major bleeding event, and stroke rate. Analysis was conducted using cox univariable regression controlling for current age. Receiver operator curve and c-statistics were produced for the CHADSVASC and HASBLED scores respectively. Results 326 people were included in this study, of whom 161 (49.5%) had TOF secondary to Pulmonic Stenosis, 126 (38.8%) had TOF secondary to Pulmonary Atresia, 25 (7.7%) had DORV, and 155 (47.7%) had PA-IVS. 227 people used warfarin (79.4%), 28 (9.8%) used apixaban, 9 (3.1%) used Rivaroxaban, 3 (1%) used Edoxaban, and 5 (1.7%) used Enoxaparin for a period of at least 30 days during the study. 13 (4.5%) people didn’t receive anticoagulation during the study. 26 people had a stroke (8.8%) while 85 people (28.6%) had a major bleeding event. Only the CHADSVASC score was significantly associated with stroke rates (HR 2.103, 95% CI 1.555 to 2.844, p<0.001). Clinical variables, such as subtype of CHD, prior conduit placement or unifocalization were not associated with stroke or major bleeding events. C-statistic for the CHADSVASC score in predicting stroke events was 0.755 (Figure 1). C-statistic for the HASBLED score in predicting major bleeding was 0.442 (Figure 2). Conclusions Among people with CHD and AF, the CHADSVASC score can robustly predict stroke events. Other clinical variables are less valuable in predicting either bleeding or strokes. The HASBLED score likely doesn’t have a role in predicting major bleeding episodes in this cohort.

Risk for appropriate ICD intervention and complications in patients implanted after an out-hospital cardiac arrest compared to patients implanted for primary and other secondary prevention indication

Abstract Background Few data are available about patients implanted with an implantable cardioverter defibrillators (ICDs) after an out-of-hospital cardiac arrest (OHCA). In particular, it is unclear if these patients have a higher risk of appropriate device therapy than patients implanted for primary and other secondary prevention. Purpose To assess if appropriate device interventions (ATP/shocks) are higher in patients implanted after OHCA compared to patients implanted for primary and secondary prevention other than OHCA. To verify also if mortality, implantation-related complications (pneumothorax, hemothorax, hematoma, cardiac tamponade), device-related complications (lead displacement and fracture, infections) and inappropriate shocks/ATP are higher in OHCA patients compared to other patients. Methods This is a retrospective multicenter international study. All the patients implanted with an ICD between January 2015 and December 2016 in the participating centers were included. Follow-up was considered concluded in case of death or at the last follow-up available until December 2023. Patients were divided according to ICD implantation indication (secondary prevention after OHCA, other secondary prevention, primary prevention). Results 1386 patients (79% males; median age 67, IQR 59-74) from 15 centers were included with a median follow-up of 83 months: 111 patients in OHCA group, 134 in other secondary prevention group and 1141 in primary prevention group. Considering the first appropriate intervention, a significant difference among the three groups was observed (Fig.1A) and, at post-hoc comparison, the OHCA group was at higher risk than primary prevention (HR 1.51, 95%CI 1.06-2.17, p=0.02), but was at similar risk than other secondary prevention (HR 0.79, 95%CI 0.51-1.23, p=0.3). This was confirmed also after correction for age, gender, history of atrial fibrillation, aetiology and multi-comorbidity (Fig.2A). However, considering the number of appropriate interventions during follow-up, the risk of OHCA group was lower than other secondary prevention (IRR 0.28, 95%CI 0.11-0.68, p<0.01) and similar to primary prevention (IRR 0.97, 95%CI 0.47-1.96, p=0.93), also after correction for the other predictors (Fig.2B). The three groups showed no differences in survival (Fig.1B), implantation-related complication, device-related complications (Fig.1C) and inappropriate shocks/ATP. Conclusion Patients implanted with an ICD after an OHCA have a risk similar to those implanted for other secondary prevention, when considering the first appropriate intervention, but a risk similar to those implanted for primary prevention when considering the number of appropriate interventions during follow-up. Our study confirms that OHCA patients represents a peculiar population with the same chance of survival and rate of complications compared to primary and other secondary prevention patients suggesting the need of more studies to improve their long-term treatment.Figure 1 (Panel A, B and C)Figure 2 (Panel A and B)

Tricuspid regurgitation in the context of severe concomitant left-sided valvular heart disease: patients characteristics and long-term clinical and interventional outcomes

Abstract Background The clinical features, therapeutical management and outcome of patients with significant tricuspid regurgitation (TR) in the context of multiple valvular disease (VD) are poorly defined. Purpose To assess the characteristics, management and long-term prognosis of a large cohort of patients with multiple VD, focusing on the context of significant TR and concomitant severe mitral or aortic disease. Methods Clinical and echocardiographic data were collected in 1183 patients with ≥moderate TR diagnosed at our centers from January 2012 to June 2020: after propensity score matching for age to create matched cohort with < 10% of absolute difference, 975 patients were included in this study and divided in 4 groups as shown in Figure 1. Primary endpoint was all-cause death (ACD), secondary endpoint was the composite of heart failure (HF) hospitalization+any valvular intervention. Results Patients with isolated TR (356, 37%) had more history of atrial fibrillation and were more often asymptomatic and with preserved left-ventricular ejection fraction (LVEF). TR+ severe MR patients (466, 48%) showed higher rates of concomitant coronary artery disease, NYHA class III/IV symptoms and larger left atrial volumes. The group of TR+ severe AS (131 patients, 13%) was characterized by older age, more comorbidities and lower LVEF. Patients with TR and severe AR (22, 2%) were younger, with larger LV dimensions and higher pulmonary pressures. Overall, in 37(4%) patients tricuspid intervention was performed: no differences were found between groups in term of frequency of concomitant or staged tricuspid valve surgical treatment (p=0.444 and p= 0.624, respectively), while left-valve only surgical treatment was more common among patients with TR and severe MR and left-valve transcatheter treatment among patients with TR and severe AS (both p<0.001). After a median follow-up of 2.8 years, the primary endpoint occured in 374 (38%) of patients, and was significantly more frequent in the group of patients with TR and severe AS (p<0.001, Figure 2). In this group, after multivariate analysis, indexed stroke volume remained independenty associated with ACD (OR 0.96, CI 0.93-0.98, p =0.040). Eventually, the secondary endpoint too was more common in patients with TR and severe AS (p<0.001, Figure 2). Conclusions In the context of significant TR, concomitant severe left-sided VD is common, and each subtype presents with different clinical features and echocardiographic phenotypes; in this scenario, TR was profoundly underteated. Long-term, patients with significant TR+ severe AS have considerable worse prognosis.Figure 1Figure 2

Prognostic implications and alterations in left atrial deformation following transcatheter aortic valve implantation for severe aortic stenosis

Abstract Background Left atrial reservoir strain (LARS) as a single parameter estimate of left ventricular (LV) diastolic dysfunction (DD), may provide important prognostic insights into patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). Purpose To evaluate the prognostic implications of pre- and post TAVI LARS-defined DD (LARS-DD) grade in patients undergoing TAVI for severe AS and its association with new-onset atrial fibrillation. Methods Pre-TAVI LARS-DD was evaluated by speckle-tracking echocardiography and was assigned as grade 0 to 1 (LARS ≥24%), grade 2 (LARS ≥19 to <24%) and grade 3 (LARS <19%). Patients were followed-up for the primary endpoint of all-cause mortality from the date of TAVI. For the secondary endpoint, patients with pre- and post-TAVI LARS measurements, no history of atrial fibrillation and with clinical/ECG follow-up following the post-TAVI follow-up echocardiogram were evaluated for the occurrence of new-onset atrial fibrillation. Results A total of 601 patients (median age 81 [76-85] years, 53% male) undergoing TAVI for severe AS were included. Overall, 169 patients (28%) were LARS-DD grade 0/1, 96 patients (16%) were LARS-DD grade 2 and 336 (56%) were LARS-DD grade 3. Over a median follow-up of 40 (IQR 26 to 58) months, a total of 258 (43%) patients died (Figure 1). In a comprehensive multivariable Cox regression model adjusted for age, sex, EuroSCORE II, New York Heart Association class III to IV symptoms, LV ejection fraction, atrial fibrillation, LA volume index and LV stroke volume index, LARS-DD grade was independently associated with all-cause mortality (adjusted HR 1.28 per one grade increase above LARS-DD grade 0/1, 95% CI 1.07 to 1.53, P=0.007). For the secondary endpoint of new-onset atrial fibrillation, a total of 285 patients were evaluated (Figure 2). On multivariable Fine and Gray regression analyses adjusting for age and LA volume index, post-TAVI LARS (SDHR 1.14 per 1% <20%, 95% CI 1.05 to 1.23, P=0.0009), rather than pre-TAVI LARS (SDHR 1.00 per 1% <20%, 95% CI 0.91 to 1.11, P=0.93) was associated with the occurrence of new-onset atrial fibrillation. Conclusions Increasing LARS-DD grade was independently associated with long-term post-TAVI survival in patients with severe AS and may enhance risk stratification. In addition, post-TAVI LARS, but not pre-TAVI LARS, was closely related to the occurrence of new-onset atrial fibrillation, likely better reflecting intrinsic LA dysfunction.Figure 1:All-Cause MortalityFigure 2:New-Onset Atrial Fibrillation

Cardiovascular disease risk in people with diabetes in the era of universal diabetes screening

Abstract Background/Introduction Traditionally, most people with diabetes have been considered at high cardiovascular disease (CVD) risk and CVD preventive treatment has been recommended for almost all patients after diagnosis. However, guidelines are increasingly recommending a more stratified approach to preventive treatment informed by predicted CVD risk. In the early 2000’s, New Zealand initiated the world-first national diabetes screening programme, as a component of a national CVD risk assessment programme, and by 2016, approximately 90% of eligible New Zealand adults had been screened. We hypothesised that in the era of universal diabetes screening, many recently diagnosed patients will be at low CVD risk and that contemporary CVD risk prediction equations would be required to accurately assess their risk. Purpose We aimed to develop sex-specific 5-year CVD risk prediction models in people with diabetes in New Zealand using a contemporary natural-population based cohort, and to characterise the distribution of CVD risk. Methods De-identified individual-level linkage of multiple health administrative datasets was undertaken to establish a cohort of almost all adults with diabetes in the northern region of New Zealand (one-third of the national population), without CVD or heart failure, and aged 30–74 years on January 1, 2014, with follow-up linkage to hospitalisations and mortality until December 31, 2018. Sex-specific models were developed to estimate the 5-year risk of CVD hospitalisation or death, with 15 pre-defined predictors, including sociodemographic variables, diabetes-related and renal function measures. Results 64,645 participants (median age: 57 years [IQR: 49–65]) were included in the final cohort, of whom 4,992 had first CVD events during 301,272 person-years follow-up. Models calibrated well in both women and men (Figure 1). Overall, increasing age; high deprivation level; smoking-related hospitalisations or use of smoking cessation medications; history of atrial fibrillation; high levels of haemoglobin A1c, total cholesterol to HDL cholesterol ratio, and albumin-to-creatinine ratio; use of blood pressure-lowering medications and insulin were associated with elevated CVD risk. Median 5-year CVD risks were 4.9% (IQR: 2.9%–8.1%) in women and 7.7% (4.8%–12.0%) in men. There was a wide range of predicted 5-year CVD risk, with 51% of women and 27% of men having a predicted risk below 5%, and 6% of women and 16% of men having a risk of 15% or above (Figure 2). Conclusions This study demonstrated marked heterogeneity in predicted CVD risk in people with diabetes in an era of universal diabetes screening. As diabetes screening is increasingly undertaken as part of a routine CVD risk assessment, these findings will have important clinical implications for accurately targeting new but expensive CVD preventive medications to the highest risk patients.

Application of anticoagulants in the perioperative period of pci for patients with a history of atrial fibrillation and NSTEMI: a real-world, large multicenter retrospective clinical study

Abstract Backgrounds The optimal management for patients with atrial fibrillation (AF) and concomitant coronary artery disease (CAD) remains unclear, particularly regarding anticoagulants use and ischemia-bleeding balance risks. This study aims to investigate the impact of perioperative anticoagulant use on patients with AF and acute non-ST-segment elevation myocardial infarction (NSTEMI). Methods Data for this study were obtained from a retrospective cohort of patients admitted to and discharged from 72 secondary and tertiary hospitals from 2010 to 2023. A total of 150,530 patients were enrolled, including 74,373 NSTEMI patients. Patients were divided into anticoagulants and non-anticoagulants groups. A total of 1,358 patients were included in the non-anticoagulant group, and 3,541 patients were included in the anticoagulant group. Patients in each group were one-to-one matched based on propensity scores using the nearest available pair matching (PSM) method with a caliper width equal to 0.01. The primary endpoints were major adverse cardiovascular and cerebrovascular adverse events (MACCE), including cardiovascular death, recurrent myocardial infarction, and stroke. Secondary endpoints included cardiovascular death, recurrent myocardial infarction, BARC type 3 bleeding, and cerebral hemorrhage. Follow-up time points were set at 1 month,3 months, and 6 months. Multivariate Cox regression models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). Results After PSM matching, each group consisted of 809 patients. The anticoagulant group had a higher proportion of males, a higher prevalence of patients with a history of Percutaneous Coronary Intervention, and hyperlipidemia, while proportions of patients with Killips classification of III/IV and history of chronic kidney disease were lower. Anticoagulant use during the perioperative period significantly reduced the occurrence of MACCE at the primary endpoint at 1 month (aHR 0.57; P < 0.001), 3 months (aHR 0.57; P = 0.023), and 6 months (aHR 0.57; P < 0.001). At the secondary endpoint, anticoagulants use was associated with a lower incidence of cardiogenic death at 1 month,3 months, and 6 months (aHR 0.55; P <0.001), (aHR 0.55; P <0.001), (aHR 0.56; P <0.001), lower risk of myocardial infarction recurrence at 3 months and 6 months (aHR 0.47; P = 0.02), (aHR 0.44; P <0.001), without increasing the risk of bleeding events, including BARC type 3 bleeding and cerebral hemorrhage. Conclusion Perioperative anticoagulant use during PCI can reduce the occurrence of cardiac death, myocardial infarction, and stroke recurrence within 6 months post-surgery without increasing bleeding events in AF and NSTEMI patients. Therefore, for patients with AF, it is recommended to consider combining anticoagulant therapy with dual antiplatelet therapy during the perioperative period, if no contraindications.

Left atrial morpho-functional parameters and their correlation with other phenotypic and functional characteristics of hypertrophic cardiomyopathy

Abstract Background Left atrial (LA) volume index (LAVI), LA reservoir strain (LARS) and total atrial conduction time (TACT) (estimated by tissue Doppler imaging) are morphological and functional parameters reflecting LA structural and electrical remodeling, connected to atrial fibrillation development and heart failure progression in various substrates. In hypertrophic cardiomyopathy (HCM), correlation of the above-mentioned parameters with other disease characteristics is not fully investigated. Purpose Aim of this study was to estimate the prevalence of atrial myopathy characteristics such as increased LAVI, impaired LARS and elongated TACT in a cohort of HCM patients without AF history and investigate their correlation with other phenotypic and functional characteristics of the disease such as left ventricular (LV) hypertrophy magnitude, fibrosis extent and diastolic dysfunction grade. Methods We included 100 HCM patients (54±21 years, 75% male, maximum wall thickness 19±3.4mm) without history of atrial fibrillation who have consecutively undergone 2D-speckle tracking echocardiography and cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE). TACT and LARS measurement is shown on left panel. Burden of fibrosis (percentage of LV mass) was defined by LGE extent (>5 standard deviations compared to nulled myocardium) in CMR slices. Results All HCM patients had preserved EF (60±7.5%), while 28 (28%) presented outflow tract obstruction and 10 (10%) diastolic dysfunction stage≥2. LGE was observed in 64 patients (64%) occupying 8±5% of left ventricular (LV) mass. Mean TACT was 140±22 msec, with LAVI being 32±16 mL/m2 and LARS 26±14%. Among HCM demographic, phenotypic and functional characteristics tested, age and LV mass index were found to be the only independent regressors of TACT (r=0.54, p<0.0005 and r=0.44, p=0.002 respectively, right upper panel), while E/E’ (r=-0.44, p=0.003) and fibrosis extent (r=0.36, p=0.02) were the strongest predictors of LARS and LAVI values respectively (right lower panel). Conclusions Atrial myopathy parameters seem to correlate with various morphological and functional characteristics of HCM. Atrial electro-mechanical delay assessed through TDI based TACT correlates significantly with LVMI, whereas LARS and LAVI are strong regressors of elasticity properties, partially expressed through diastolic function and underlying fibrosis.

Global myocardial work index is an independent predictor of functional capacity on 6-minute walk test in stable non-ischaemic cardiomyopathy

Abstract Background Reduction in 6-minute walk test distance (6MWD) in heart failure (HF) is associated with impaired quality of life and adverse cardiovascular outcomes. Myocardial work (MW) indices are novel non-invasive measures of left ventricular (LV) function which characterise myocardial contractile efficiency and energy utility. Purpose We aim to assess the predictive capacity of MW indices for functional capacity in stable non-ischaemic cardiomyopathy (NICM). Methods We prospectively recruited consecutive patients with stable NICM from our HF service from January 2021 to December 2023. All patients received optimal guideline direct therapy (OGDT) for 3-months before undergoing a comprehensive transthoracic echocardiogram and functional assessment with 6-minute walk test (6MWT). We excluded patients with prior cardiac surgery, severe airways disease, valvular heart disease, and those in atrial fibrillation (AF) or had mechanical limitations to their mobility at time of 6MWT. We collected demographic, clinical, and echocardiographic factors to identify the determinates of reduced 6MWD defined as <300 metres. Results Of 249-patients included (69.9% male; age 57.3±16.5yrs), 65-patients had reduced 6MWD. They were significantly older (62.3±17.2 vs 55.5±16.0yrs, p=0.005), had shorter height (166.3±10.3 vs 171.3±9.8cm, p=0.001), higher prevalence of AF history (39.1 vs 21.4%, p=0.001), lower LV-ejection-fraction (38.1±13.3 vs 43.3±10.2%, p=0.001), lower LV-global-longitudinal-strain (LV-GLS; 10.5±4.4 vs 12.7±3.9%, p<0.001), lower global-work-index (GWI; 943±487 vs 1230±455mmHg%, p<0.001), lower global-constructive-work (GCW; 1286±561 vs 1590±494mmHg%, p<0.001), lower global-work-efficiency (GE; 81.2±9.9 vs 85.4±8.1mmHg%, p=0.04), larger indexed left atrial volume (LAV; 45.0±18.4 vs 40.1±24.5ml/m2, p=0.038), higher E/e’ ratio (14.6±8.9 vs 11.8±6.0, p=0.003), and lower right-ventricular-free-wall-strain (RV-FWS; 19.2±6.7 vs 21.8±6.4, p=0.008; Table 1.). On receiver-operating-characteristics-curve analysis, GWI best predicted 6MWD reduction (Figure 1; AUC 0.68) compared to GCW, GE, LVEF and LVGLS (AUC: 0.62, 0.40, 0.62, and 0.62 respectively). Accounting for covariates, our multiple regression was run to predict 6MWD from age, height, AF history, LAV, E/e’, GWI and RV-FWS. These variables statistically significantly predicted 6MWD, F(4,239)=23.5, p<0.001, R2=0.34). With each 100mmHg% rise in GWI being independently associated with a 6.5m increase in 6MWD. Conclusion GWI was independently associated with 6MWD in our cohort of NICM patients on OGDT. MW indices provide some mechanistic insights into exercise capacity in patients with NICM.Table 1.Baseline CharacteristicsFigure 1.ROC of GWI Discriminating 6MWD