Characteristics of patients with atrial high rate episodes detected by implanted defibrillator and resynchronization devices.

AIMS: Atrial high rate episodes (AHREs) are associated with increased risks of thromboembolism and cardiovascular mortality. However, the clinical characteristics of patients developing AHRE of various durations are not well studied. METHODS AND RESULTS: This was an ancillary analysis of the multicentre, randomized IMPACT trial. In the present analysis, we classified patients according to the duration of AHRE ≤6 min, >6 min to ≤6 h, >6 to ≤24 h and >24 h, and investigated the association between clinical factors and the development of each duration of AHRE. Of 2718 patients included in the trial, 945 (34.8%) developed AHRE. The incidence rates of each AHRE duration category were 5.4/100, 12.0/100, 6.8/100, and 3.3/100 patient-years, respectively. The incidence rates of AHRE >6 h were significantly higher in patients at high risk of thromboembolism (CHADS2 score ≥3) compared to those at low risk (CHADS2 score 1 or 2). Using Cox regression analysis, age ≥65 years and history of atrial fibrillation (AF) and/or atrial flutter (AFL) were risk factors for AHRE >6 min. In addition, hypertension was associated with AHRE >24 h (hazard ratio 2.13, 95% confidence interval 1.24-3.65, P = 0.006). CONCLUSION: Atrial high rate episode >6 min to ≤6 h were most prevalent among all AHRE duration categories. Longer AHREs were more common in patients at risk of thromboembolism. Age and history of AF/AFL were risk factors for AHRE >6 min. Furthermore, hypertension showed a strong impact on the development of AHRE >24 h rather than age.

Predicting therapies in Japanese hypertrophic cardiomyopathy patients with an implantable cardioverter-defibrillator using the 2014 European Society of Cardiology guidelines.

Previous studies have shown that the sudden cardiac death (SCD) prediction model proposed by the 2014 European Society of Cardiology (ESC) guideline (5-Year Risk-SCD) was validated in European patients with hypertrophic cardiomyopathy (HCM). However, there are limited data on Asian patients with HCM. We assessed the validity of the estimated 5-Year Risk-SCD in Japanese HCM patients with an implantable cardioverter-defibrillator (ICD) using the2014 ESC guidelines. We retrospectively examined data of 492 consecutive Japanese patients with an ICD. Sixty-two Japanese HCM patients with an ICD were enrolled in this study, and 50 patients (81%) were followed up for ≥ 5 years. We analyzed the characteristics and outcomes of these 50 patients. We investigated the incidence of appropriate ICD therapy as categorized by the ESC guideline and compared the 5-Year Risk-SCD with the 5-year rate of appropriate shock therapies. Based on the 2012 Japanese Circulation Society guideline and the 2011guidelines of the American Heart Association and American College of Cardiology Foundation, 10 and 40 patients met classes I and IIa of the ICD recommendation, respectively. However, only 18 (36%) patients were classified into class I or IIa of the ESC guideline. Among 50 patients followed up for ≥ 5 years after ICD implantation, the incidences of appropriate ICD therapies for classes I, IIa, IIb, and III indications based on the 2014 ESC guideline were 50%, 38%, 17%, and 0%, respectively. Risk stratification for SCD using 5-Year Risk-SCD is valid in Japanese HCM patients with an ICD, and the 2014 ESC guideline might be useful for the indication of ICD implantation in Japan.

Guideline-Adherent Treatment for Stroke and Death in Atrial Fibrillation Patients From UK and Japanese AF Registries.

BACKGROUND: Guideline-adherent antithrombotic treatment (ATT) reduces the risk of stroke and death in patients with atrial fibrillation (AF). However, the effect of ATT adherence among different ethnicities remains uncertain. We compared the prognosis of AF patients in Japan and the UK according to guideline adherence status.Methods and Results:We compared the clinical characteristics and outcomes of AF patients from the Fushimi AF registry (Japan; n=4,239) and the Darlington AF registry (UK; n=2,259). ATT adherence was assessed against the Japanese Circulation Society Guidelines and UK National Institute for Health and Care Excellence guidelines. The rates of guideline-adherent ATT were 58.6% and 50.8% in the Fushimi and Darlington registries, respectively. There was no significant difference in 1-year stroke rates between Fushimi and Darlington (2.6% vs. 3.0%, P=0.342). On multivariate logistic regression analysis, non-guideline adherent-ATT was significantly associated with an increased risk of stroke (odds ratio [OR]: 1.69, 95% confidence interval [CI]: 1.21-2.34, P=0.002 for undertreatment, OR: 2.13, 95% CI: 1.19-3.80, P=0.010 for overtreatment). No significant interaction for ATT and the 2 populations was found in the incidence of stroke, all-cause death, and the composite outcome. CONCLUSIONS: Approximately half of the AF patients received optimal ATT according to guideline recommendations, which was associated with a lower risk of stroke. Furthermore, there was no interaction for the 2 populations and the influence of ATT adherence.

Shortening of the atrial-His bundle interval during atrial pacing as a predictor of successful ablation for typical atrioventricular nodal re-entrant tachycardia.

Aims: Shortening of the atrial-His bundle (AH) interval during the sinus rhythm is occasionally observed after slow pathway ablation for atrioventricular nodal re-entrant tachycardia (AVNRT). In addition, high-rate atrial pacing is useful for avoiding atrioventricular block. We hypothesized that shortening of the AH interval during slow pathway ablation under high-rate atrial pacing would lead to successful ablation of typical AVNRT. Methods and results: This retrospective study included 37 patients in whom successful ablation of typical AVNRT was performed under atrial pacing. The AH interval was measured immediately before the first radiofrequency (RF) application and immediately after the last RF application, prior to the first induction. Twenty-five of 37 patients achieved procedural success at the first induction (i.e. successful group). No patients developed a prolonged AH interval or atrioventricular block. The AH interval was shortened by an average of 14.6 ± 7.7 and 1.8 ± 1.2 ms in the successful and other patient groups, respectively (P < 0.01). An AH interval decrease of > 10 ms was observed in 23 of 27 (85%) patients in the successful group, whereas all other patients had an AH interval decrease of < 5 ms. Conclusion: Shortening of the AH interval during high-rate atrial pacing is a predictor of the successful ablation for typical AVNRT.

Prospective survey of implantable defibrillator shock anxiety in Japanese patients: Results from the DEF-Chiba study.

BACKGROUND: Patient-reported outcomes of implantable cardioverter defibrillator (ICD), such as those with shock anxiety, have emerged as important endpoints that are related to quality of life (QOL), but they have not been well studied in a sample of the Japanese population. Therefore, we prospectively examined changes in shock anxiety in a large sample of Japanese patients with an ICD. METHODS: We recruited 214 consecutive patients with an ICD who visited the outpatient clinic. At registration and 12 months later, all patients completed the Florida Shock Anxiety Scale (FSAS) questionnaire to allow us to examine changes in shock anxiety over the course of the first year after registration. RESULTS: During the 12-month follow-up period, 10.5% of the patients received ICD shock therapy. Female sex, secondary prevention, and experience of ICD shock therapy were associated with high FSAS scores at registration. The FSAS scores in both patients with appropriate and inappropriate shock were significantly higher at the 12-month follow-up interval than at registration, and there was no significant difference in the extent of changes in FSAS scores (Δ = 5.2 ± 5.1 and Δ = 6.3 ± 9.9, respectively, P = 0.62). CONCLUSIONS: Female sex, secondary prevention, and experience of ICD shock therapy are important risk factors affecting shock anxiety in Japanese patients. Attention should be paid to the after-effects of ICD shock in these patients, regardless of the shock type, with particular attention to women and patients who require secondary prevention.

Multi-Ancestry Polygenic Risk Score for Coronary Heart Disease Based on an Ancestrally Diverse Genome-Wide Association Study and Population-Specific Optimization.

BACKGROUND: Predictive performance of polygenic risk scores (PRS) varies across populations. To facilitate equitable clinical use, we developed PRS for coronary heart disease (CHD; PRSCHD) for 5 genetic ancestry groups. METHODS: We derived ancestry-specific and multi-ancestry PRSCHD based on pruning and thresholding (PRSPT) and ancestry-based continuous shrinkage priors (PRSCSx) applied to summary statistics from the largest multi-ancestry genome-wide association study meta-analysis for CHD to date, including 1.1 million participants from 5 major genetic ancestry groups. Following training and optimization in the Million Veteran Program, we evaluated the best-performing PRSCHD in 176,988 individuals across 9 diverse cohorts. RESULTS: Multi-ancestry PRSPT and PRSCSx outperformed ancestry-specific PRSPT and PRSCSx across a range of tuning values. Two best-performing multi-ancestry PRSCHD (ie, PRSPTmult and PRSCSxmult) and 1 ancestry-specific (PRSCSxEUR) were taken forward for validation. PRSPTmult demonstrated the strongest association with CHD in individuals of South Asian ancestry and European ancestry (odds ratio per 1 SD [95% CI, 2.75 [2.41-3.14], 1.65 [1.59-1.72]), followed by East Asian ancestry (1.56 [1.50-1.61]), Hispanic/Latino ancestry (1.38 [1.24-1.54]), and African ancestry (1.16 [1.11-1.21]). PRSCSxmult showed the strongest associations in South Asian ancestry (2.67 [2.38-3.00]) and European ancestry (1.65 [1.59-1.71]), lower in East Asian ancestry (1.59 [1.54-1.64]), Hispanic/Latino ancestry (1.51 [1.35-1.69]), and the lowest in African ancestry (1.20 [1.15-1.26]). CONCLUSIONS: The use of summary statistics from a large multi-ancestry genome-wide meta-analysis improved the performance of PRSCHD in most ancestry groups compared with single-ancestry methods. Despite the use of one of the largest and most diverse sets of training and validation cohorts to date, improvement of predictive performance was limited in African ancestry. This highlights the need for larger genome-wide association study datasets of underrepresented populations to enhance the performance of PRSCHD.

A Multi-Ancestry Polygenic Risk Score for Coronary Heart Disease Based on an Ancestrally Diverse Genome-Wide Association Study and Population-Specific Optimization.

Background: Predictive performance of polygenic risk scores (PRS) varies across populations. To facilitate equitable clinical use, we developed PRS for coronary heart disease (PRSCHD) for 5 genetic ancestry groups. Methods: We derived ancestry-specific and multi-ancestry PRSCHD based on pruning and thresholding (PRSP+T) and continuous shrinkage priors (PRSCSx) applied on summary statistics from the largest multi-ancestry genome-wide meta-analysis for CHD to date, including 1.1 million participants from 5 continental populations. Following training and optimization of PRSCHD in the Million Veteran Program, we evaluated predictive performance of the best performing PRSCHD in 176,988 individuals across 9 cohorts of diverse genetic ancestry. Results: Multi-ancestry PRSP+T outperformed ancestry specific PRSP+T across a range of tuning values. In training stage, for all ancestry groups, PRSCSx performed better than PRSP+T and multi-ancestry PRS outperformed ancestry-specific PRS. In independent validation cohorts, the selected multi-ancestry PRSP+T demonstrated the strongest association with CHD in individuals of South Asian (SAS) and European (EUR) ancestry (OR per 1SD[95% CI]; 2.75[2.41-3.14], 1.65[1.59-1.72]), followed by East Asian (EAS) (1.56[1.50-1.61]), Hispanic/Latino (HIS) (1.38[1.24-1.54]), and weakest in African (AFR) ancestry (1.16[1.11-1.21]). The selected multi-ancestry PRSCSx showed stronger associacion with CHD in comparison within each ancestry group where the association was strongest in SAS (2.67[2.38-3.00]) and EUR (1.65[1.59-1.71]), progressively decreasing in EAS (1.59[1.54-1.64]), HIS (1.51[1.35-1.69]), and lowest in AFR (1.20[1.15-1.26]). Conclusions: Utilizing diverse summary statistics from a large multi-ancestry genome-wide meta-analysis led to improved performance of PRSCHD in most ancestry groups compared to single-ancestry methods. Improvement of predictive performance was limited, specifically in AFR and HIS, despite use of one of the largest and most diverse set of training and validation cohorts to date. This highlights the need for larger GWAS datasets of AFR and HIS individuals to enhance performance of PRSCHD.

Cross-ancestry genome-wide analysis of atrial fibrillation unveils disease biology and enables cardioembolic risk prediction.

Atrial fibrillation (AF) is a common cardiac arrhythmia resulting in increased risk of stroke. Despite highly heritable etiology, our understanding of the genetic architecture of AF remains incomplete. Here we performed a genome-wide association study in the Japanese population comprising 9,826 cases among 150,272 individuals and identified East Asian-specific rare variants associated with AF. A cross-ancestry meta-analysis of >1 million individuals, including 77,690 cases, identified 35 new susceptibility loci. Transcriptome-wide association analysis identified IL6R as a putative causal gene, suggesting the involvement of immune responses. Integrative analysis with ChIP-seq data and functional assessment using human induced pluripotent stem cell-derived cardiomyocytes demonstrated ERRg as having a key role in the transcriptional regulation of AF-associated genes. A polygenic risk score derived from the cross-ancestry meta-analysis predicted increased risks of cardiovascular and stroke mortalities and segregated individuals with cardioembolic stroke in undiagnosed AF patients. Our results provide new biological and clinical insights into AF genetics and suggest their potential for clinical applications.

Epidemiology of subclinical atrial fibrillation in patients with cardiac implantable electronic devices: A systematic review and meta-regression.

BACKGROUND: In recent years, attention to subclinical atrial fibrillation (SCAF), defined as the presence of atrial high-rate episodes (AHREs), in patients with cardiac implantable electronic devices (CIEDs), has gained much interest as a determinant of clinical AF and stroke risk. We aim to perform a systematic review and meta-regression of the available scientific evidence regarding the epidemiology of SCAF in patients receiving CIEDs. METHODS: PubMed and EMBASE were searched for all studies documenting the prevalence of AHREs in patients (n=100 or more, <50% with history of AF) with CIEDs from inception to 20th August 2021, screened by two independent blind reviewers. This study was registered in PROSPERO: CRD42019106994. RESULTS: Among the 2614 results initially retrieved, 54 studies were included, with a total of 72,784 patients. Meta-analysis of included studies showed a pooled prevalence of SCAF of 28.1% (95%CI: 24.3-32.1%), with high heterogeneity between studies (I2=98%). A multivariable meta-regression was able to explain significant proportion of heterogeneity (R2=61.9%, p<0.001), with age and follow-up time non-linearly, directly and independently associated with occurrence of SCAF. Older age, higher CHA2DS2-VASc score, history of AF, hypertension, CHF, and stroke/TIA were all associated with SCAF occurrence. CONCLUSIONS: In this systematic review and meta-regression analysis, SCAF was frequent among CIED recipients and was non-linearly associated with age and follow-up time. Older age, higher thromboembolic risk, and several cardiovascular comorbidities were associated with presence of SCAF.

Deep learning-based age estimation from chest X-rays indicates cardiovascular prognosis.

BACKGROUND: In recent years, there has been considerable research on the use of artificial intelligence to estimate age and disease status from medical images. However, age estimation from chest X-ray (CXR) images has not been well studied and the clinical significance of estimated age has not been fully determined. METHODS: To address this, we trained a deep neural network (DNN) model using more than 100,000 CXRs to estimate the patients' age solely from CXRs. We applied our DNN to CXRs of 1562 consecutive hospitalized heart failure patients, and 3586 patients admitted to the intensive care unit with cardiovascular disease. RESULTS: The DNN's estimated age (X-ray age) showed a strong significant correlation with chronological age on the hold-out test data and independent test data. Elevated X-ray age is associated with worse clinical outcomes (heart failure readmission and all-cause death) for heart failure. Additionally, elevated X-ray age was associated with a worse prognosis in 3586 patients admitted to the intensive care unit with cardiovascular disease. CONCLUSIONS: Our results suggest that X-ray age can serve as a useful indicator of cardiovascular abnormalities, which will help clinicians to predict, prevent and manage cardiovascular diseases.

Chest X-ray is one of the most widely used medical imaging tests worldwide to diagnose and manage heart and lung diseases. In this study, we developed a computer-based tool to predict patients' age from chest X-rays. The tool precisely estimated patients' age from chest X-rays. Furthermore, in patients with heart failure and those admitted to the intensive care unit for cardiovascular disease, elevated X-ray age estimated by our tool was associated with poor clinical outcomes, including readmission for heart failure or death from any cause. With further testing, our tool may help clinicians to predict outcomes in patients with heart disease based on a simple chest X-ray.

The Evolving Story in the Genetic Analysis for Heart Failure.

Genomic studies of cardiovascular diseases have achieved great success, not only in Mendelian genetic diseases such as hereditary arrhythmias and cardiomyopathies, but also in common diseases such as ischemic heart disease and atrial fibrillation. However, only limited success has been achieved in heart failure due to the complexity of its disease background. In this paper, we will review the genetic research for heart failure to date and discuss how we can discover new aspects of heart failure from the viewpoint of genomic perspective.

Genetic Analysis for Coronary Artery Disease Toward Diverse Populations.

Coronary artery disease is one of the leading causes of death in the world, and as such, it is one of the diseases for which genetic analyses have been actively conducted. In the early days, analyses of families with the aggregation of early-onset myocardial infarction, such as those with familial hypercholesterolemia, was the main focus, but since the practical application of genome-wide association study, the analysis of coronary artery disease as a common disease has progressed, and many disease-susceptibility loci have been identified. In addition, with the advancement of technologies, it has become possible to identify relatively rare genetic variants in a population-based analysis. These advances have not only revealed the detailed disease mechanisms but have also enabled the quantification of individual genetic risk and the development of new therapeutic agents. In this paper, some of those items, which are important to know in the current genetic analyses for coronary artery disease, are discussed.

Identifying At-Risk Patients for Sustained Atrial High-Rate Episodes Using the C2HEST Score: The West Birmingham Atrial Fibrillation Project.

Background Sustained atrial high-rate episodes (SAHREs) among individuals with a cardiac implantable electronic device are associated with an increased risk of adverse outcomes. Risk stratification for the development of SAHREs has never been investigated. We aimed to assess the performance of the C2HEST (coronary artery disease or chronic obstructive pulmonary disease [1 point each], hypertension [1 point], elderly [age ≥75 years, 2 points], systolic heart failure [2 points], thyroid disease [1 point]) score in predicting SAHREs in patients with cardiac implantable electronic devices without atrial fibrillation. Methods and Results Five Hundred consecutive patients with cardiac implantable electronic devices in the West Birmingham Atrial Fibrillation Project in the United Kingdom were followed since the procedure to observe the development of SAHREs, defined by atrial high-rate episodes lasting >24 hours. Risk factors and incidence of SAHREs were analyzed. The predictive value of the C2HEST score for SAHRE prediction was evaluated. Over a mean follow-up of 53.1 months, 44 (8.8%) patients developed SAHREs. SAHREs were associated with higher all-cause mortality (P<0.001) and ischemic stroke (P=0.001). Age and heart failure were associated with SAHRE occurrence. The incidence of SAHREs increased by the C2HEST score (39% higher risk per point increase). Among patients with a C2HEST score ≥4, the incidence of SAHREs was 3.62% per year (95% CI, 2.14-5.16). The C2HEST score had moderate predictive capability (area under the curve, 0.73; 95% CI, 0.64-0.81) and discriminative ability (log-rank P=0.003), which was better than other clinical scores (CHA2DS2-VASc, CHADS2, HATCH). Conclusions The C2HEST score predicted SAHRE incidence in patients without atrial fibrillation who had an cardiac implantable electronic device, with the highest risk seen in patients with a C2HEST score ≥4 The benefit of using the C2HEST score in clinical practice in this patient population needs further investigation.

Peak deflection index as a predictor of a free-wall implantation of contemporary leadless pacemakers.

BACKGROUND: Leadless pacemakers are an effective treatment for bradycardia. However, some cases exhibit pericardial effusions, presumably associated with device implantations on the right ventricular free-wall. The present study was carried out to find the ECG features during ventricular pacing with a Micra, which enabled distinguishing free-wall implantations from septal implantations without using imaging modalities. METHODS: Thirty-one consecutive patients who received Micra implantations in our facility were enrolled. The location of the device in the right ventricle was evaluated using echocardiography or computed tomography in order to determine whether the device was implanted on the septum (Sep group), apex (Apex group), or free-wall (FW group). The differences in the 12-lead ECG during ventricular pacing by the Micra were analyzed between the Sep and FW groups. RESULTS: The body of the Micra was clearly identifiable in 22 patients. The location of the device was classified into Sep in 12 patients, Apex in 4, and FW in 6. The mean age was highest in the FW and lowest in the Sep group (82.7 ± 6.6 vs. 72.8 ± 8.7 years, p = 0.027). The peak deflection index (PDI) was significantly larger in the FW group than Sep/Apex group in lead V1 (Sep: 0.505 ± 0.010, Apex: 0.402 ± 0.052, FW: 0.617 ± 0.043, p = 0.004) and lead V2 (Sep: 0.450 ± 0.066, Apex: 0.409 ± 0.037, FW: 0.521 ± 0.030, p = 0.011), whereas there was no difference in the QRS duration, transitional zone, and QRS notching. CONCLUSION: The PDI in V1 could be useful for predicting implantations of Micra devices on the free-wall and may potentially stratify the risk of postprocedural pericardial effusions.