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Abstract Background Under‐sensing (US) in implantable loop recorders (ILRs) interferes with the accurate diagnosis of arrhythmia, but there is little information available on the details of US of ILRs. The aim of this study was to clarify the frequency of US in patients with ILRs and to investigate the predictors of US in ILRs prior to implantation. Methods and Results We studied 46 consecutive patients implanted ILR. During the mean follow‐up period of 499 ± 363 days, 15 events of US were observed in five patients. There were no significant differences in patient characteristics between patients with and without US. In standard 12‐lead electrocardiogram (ECG), QRS complex amplitude in anterolateral chest leads (V2 to V5) were significantly lower in patients with than without US (V2: 0.88 [0.66, 1.22] mV vs. 1.67 [1.23, 2.29] mV, p = .010 V3: 1.25 [1.00, 1.26] mV vs. 1.90 [1.41, 2.29] mV, p = .013; V4: 1.14 [0.96, 1.38] mV vs. 1.93 [1.65, 2.64] mV, p = .023; V5: 0.57 [0.50, 0.75] mV vs. 1.60 [1.20, 1.98] mV, p = .011, respectively). ROC curve analysis showed that cut‐off values of 1.30 mV of QRS complex amplitude in V2, 1.26 mV of that in V3, and 0.75 mV of that in V5 had moderate accuracy for predicting US (V2: sensitivity 68%, specificity 100%, area under the curve [AUC] 0.86; V3: sensitivity 85%, specificity 80%, AUC 0.85; V5: sensitivity 98%, specificity 80%, AUC 0.85, respectively). Conclusions US was observed in 10.9% patients with an ILR. QRS complex amplitude in anterolateral chest leads (V2 to V5) on ECG might be useful for predicting US in patients with ILRs.

Abstract Aims Application of the latent class analysis to acute heart failure with preserved ejection fraction (HFpEF) showed that the heterogeneous acute HFpEF patients can be classified into four distinct phenotypes with different clinical outcomes. This model‐based clustering required a total of 32 variables to be included. However, this large number of variables will impair the clinical application of this classification algorithm. This study aimed to identify the minimal number of variables for the development of optimal subphenotyping model. Methods and results This study is a post hoc analysis of the PURSUIT‐HFpEF study (N = 1095), a prospective, multi‐referral centre, observational study of acute HFpEF [UMIN000021831]. We previously applied the latent class analysis to the PURSUIT‐HFpEF dataset and established the full 32‐variable model for subphenotyping. In this study, we used the Cohen's kappa statistic to investigate the minimal number of discriminatory variables needed to accurately classify the phenogroups in comparison with the full 32‐variable model. Cohen's kappa statistic of the top‐X number of discriminatory variables compared with the full 32‐variable derivation model showed that the models with ≥16 discriminatory variables showed kappa value of >0.8, suggesting that the minimal number of discriminatory variables for the optimal phenotyping model was 16. The 16‐variable model consists of C‐reactive protein, creatinine, gamma‐glutamyl transferase, brain natriuretic peptide, white blood cells, systolic blood pressure, fasting blood sugar, triglyceride, clinical scenario classification, infection‐triggered acute decompensated HF, estimated glomerular filtration rate, platelets, neutrophils, GWTG‐HF (Get With The Guidelines‐Heart Failure) risk score, chronic kidney disease, and CONUT (Controlling Nutritional Status) score. Characteristics and clinical outcomes of the four phenotypes subclassified by the minimal 16‐variable model were consistent with those by the full 32‐variable model. The four phenotypes were labelled based on their characteristics as ‘rhythm trouble’, ‘ventricular‐arterial uncoupling’, ‘low output and systemic congestion’, and ‘systemic failure’, respectively. Conclusions The phenotyping model with top 16 variables showed almost perfect agreement with the full 32‐variable model. The minimal model may enhance the future clinical application of this clustering algorithm.

Abstract Aims The effectiveness of angiotensin‐converting enzyme inhibitors (ACE‐I) and angiotensin II receptor blockers (ARB) has not been demonstrated in patients with heart failure with preserved ejection fraction (HFpEF). We recently reported significant interaction between the use of ACE‐I and/or ARB (ACE‐I/ARB) and frailty on prognosis in patients with HFpEF. In the present study, we examined the association between ACE‐I/ARB and prognosis in patients with HFpEF stratified by the presence or absence of frailty. Methods and results We examined the association between the use of ACE‐I/ARB and prognosis according to the presence [Clinical Frailty Scale (CFS) ≥ 5] or absence (CFS ≤ 4) of frailty in patients with HFpEF in a post hoc analysis of registry data. Primary endpoint was the composite of all‐cause mortality and heart failure admission. Secondary endpoints were all‐cause mortality and heart failure admission. Of 1059 patients, median age was 83 years and 45% were male. Kaplan–Meier analysis showed that the risk of composite endpoint (log‐rank P = 0.001) and all‐cause death (log‐rank P = 0.005) in patients with ACE‐I/ARB was lower in those with CFS ≥ 5, but similar between patients with and without ACE‐I/ARB in patients with CFS ≤ 4 (composite endpoint: log‐rank P = 0.830; all‐cause death: log‐rank P = 0.192). In a multivariable Cox proportional hazards model, use of ACE‐I/ARB was significantly associated with lower risk of the composite endpoint [hazard ratio (HR) = 0.52, 95% confidence interval (CI) = 0.33–0.83, P = 0.005] and heart failure admission (HR = 0.45, 95% CI = 0.25–0.83, P = 0.010) in patients with CFS ≥ 5, but not in patients with CFS ≤ 4 (composite endpoint: HR = 1.41, 95% CI = 0.99–2.02, P = 0.059; heart failure admission: HR = 1.43, 95% CI = 0.94–2.18, P = 0.091). The association between ACE‐I or ARB and prognosis did not significantly differ by CFS (CFS ≤ 4: log‐rank P = 0.562; CFS ≥ 5: log‐rank P = 0.100, for with ACE‐I vs. ARB, respectively). Adjusted HRs for CFS 1–4 were higher than 1.0 but were

Abstract Aims Frailty is associated with prognosis of cardiovascular diseases. However, the significance of frailty in patients with heart failure with preserved ejection fraction (HFpEF) remains to be elucidated. The purpose of this study was to examine the prognostic significance of the Clinical Frailty Scale (CFS) in real‐world patients with HFpEF using data from a prospective multicentre observational study of patients with HFpEF (PURSUIT‐HFpEF study). Method and Results We classified 842 patients with HFpEF enrolled in the PURSUIT‐HFpEF study into two groups using CFS. The registry enrolled patients hospitalized with a diagnosis of decompensated heart failure. Median age was 82 [interquartile range: 77, 87], and 45% of the patients were male. Of 842 patients, 406 were classified as high CFS (CFS ≥ 4, 48%) and 436 as low CFS (CFS ≤ 3, 52%). The primary endpoint was the composite of all‐cause mortality and heart failure admission. Secondary endpoints were all‐cause mortality and heart failure admission. Patients with high CFS were older (85 vs. 79 years, P

Background Modification of arrhythmogenic substrates with extensive ablation comprising linear and/or complex fractional atrial electrogram ablation in addition to pulmonary vein isolation (PVI‐plus) can theoretically reduce the recurrence of atrial fibrillation. The DR‐FLASH score (score based on diabetes mellitus, renal dysfunction, persistent form of atrial fibrillation, left atrialdiameter >45 mm, age >65 years, female sex, and hypertension) is reportedly useful for identifying patients with arrhythmogenic substrates. We hypothesized that, in patients with persistent atrial fibrillation, the DR‐FLASH score can be used to classify patients into those who require PVI‐plus and those for whom a PVI‐only strategy is sufficient. Methods and Results This study is a post hoc subanalysis of the a multicenter, randomized controlled, noninferiority trial investigating efficacy and safety of pulmonary vein isolation alone for recurrence prevention compared with extensive ablation in patients with persistent atrial fibrillation (EARNEST‐PVI trial). This analysis focuses on the relationship between DR‐FLASH score and the efficacy of different ablation strategies. We divided the population into 2 groups based on a DR‐FLASH score of 3 points. A total of 469 patients were analyzed. Among those with a DR‐FLASH score >3 (N=279), the event rate of atrial arrhythmia recurrence was significantly lower in the PVI‐plus arm than in the PVI‐only arm (hazard ratio [HR], 0.45 [95% CI, 0.28–0.72]; P3 and DR‐FLASH score ≤3 (P value for interaction=0.020). Conclusions The DR‐FLASH score is a useful tool for deciding the catheter ablation strategy for patients with persistent atrial fibrillation. Registration URL: https://clinicaltrials.gov; Unique identifier: NCT03514693.

Background Stent thrombosis (ST) remains a significant medical issue. In particular, longer‐term mortality and clinical predictors after ST occurrence have yet to be elucidated. Methods and Results This was a multicenter, retrospective, observational study. A total of 187 definite ST cases from January 2008 to December 2017 were enrolled, and the long‐term clinical outcomes were investigated. The primary outcome measure was the cumulative mortality after ST occurrence. In addition, independent predictors of mortality were assessed. Among the stent types causing ST, bare‐metal stent, first‐generation drug‐eluting stent, second‐generation drug‐eluting stent, and third‐generation drug‐eluting stent comprised 31.0%, 19.3%, 36.9%, and 6.4% of cases, respectively. Median duration from stent implantation to ST was 680.5 (interquartile range, 33.8–2450.5) days. Cumulative mortality was 14.6%, 17.4%, 21.2%, 24.4%, and 33.8% at 1, 2, 3, 5 and 10 years, respectively. The cumulative mortality did not significantly differ by type of stent, and mortality of late ST was higher than that of early ST and very late ST; however, it did not reach statistical significance after the multivariate analysis. Independent predictors of mortality were hemodialysis (hazard ratio [HR], 7.80; 95% CI, 3.07–19.81; P

Background The previous large‐scale randomized controlled trial showed that routine thrombus aspiration (TA) during percutaneous coronary intervention (PCI) was associated with an increased risk of stroke. However, real‐world clinical evidence is still limited. Methods and Results We investigated the association between manual TA and stroke risk during primary PCI in the OACIS (Osaka Acute Coronary Insufficiency Study) database (N=12 093). The OACIS is a prospective, multicenter registry of myocardial infarction. The primary end point of the present study is stroke at 7 days. A total of 9147 patients who underwent primary PCI within 24 hours of hospitalization were finally analyzed (TA group, n=4448, versus non‐TA group, n=4699 patients). TA was independently associated with risk of stroke at 7 days (odds ratio [OR], 1.92 [95% CI, 1.19‒3.12]; P=0.008) in the simple logistic regression model, while the multilevel random effects logistic regression model with hospital treated as a random effect showed that manual TA was not associated with incremental risk of stroke at 7 days (OR, 0.91 [95% CI, 0.71‒1.16]; P=0.435). The 7‐day stroke risk of manual TA was significantly heterogeneous in different institutions (P for interaction=0.007). Conclusions Manual TA during primary PCI for patients with acute myocardial infarction was independently associated with the overall increased risk of periprocedural stroke. However, this result was substantially skewed because of institution specific risk variation, suggesting that the periprocedural stroke may be preventable by prudent PCI procedure or appropriate periprocedural management. Registration URL: https://upload.umin.ac.jp/cgi‐open‐bin/ctr_e/ctr_view.cgi?recptno=R000005464. Unique identifier: UMIN000004575.

Background The female preponderance in heart failure with preserved ejection fraction (HFpEF) is a distinguishing feature of this disorder, but the association of sex with degree of diastolic dysfunction and clinical outcomes among individuals with HFpEF remains unclear. Methods and Results We conducted a prospective, multicenter, observational study of patients with HFpEF (PURSUIT‐HFpEF [Prospective Multicenter Observational Study of Patients with Heart Failure with Preserved Ejection Fraction]: UMIN000021831). Between 2016 and 2019, 871 patients were enrolled from 26 hospitals (follow‐up: 399±349 days). We investigated sex‐related differences in diastolic dysfunction and postdischarge clinical outcomes in patients with HFpEF. The echocardiographic end point was diastolic dysfunction according to American Society of Echocardiography/European Association of Cardiovascular Imaging criteria. The clinical end point was a composite of all‐cause death and heart failure readmission. Women accounted for 55.2% (481 patients) of the overall cohort. Compared with men, women were older and had lower prevalence rates of hypertension, coronary artery disease, and chronic kidney disease. Women had diastolic dysfunction more frequently than men (52.8% versus 32.0%, P

We evaluated the utility of single nucleotide polymorphism (SNP) markers for parentage testing in Breton (BR) and Percheron (PR) horses in Japan using the proposed International Society for Animal Genetics (P-ISAG) 147 SNP panel and 414 autosomal SNPs. Genomic DNA was extracted from 98 horses of two breeds, BR (n = 47) and PR (n = 51), and sequenced using next-generation sequencing. The average minor allele frequencies for the P-ISAG panel for BR and PR were 0.306 and 0.301, respectively. The combined probabilities of exclusion (PEs) given two parents and one offspring: exclude a relationship (PE01) and given one parent and one offspring: exclude their relationship (PE02) were over 0.9999 for both breeds. Using the P-ISAG panel, no exclusion or doubtful cases were identified in 35 valid parent-offspring pairs, suggesting that the P-ISAG panel is helpful for parentage verification in both breeds. In contrast, as 0.18% of falsely accepted parentages were observed in the parentage discovery cases, additional markers such as the combination of the P-ISAG panel and 414 autosomal SNPs (561-SNP set) presented here should be used to identify valid parent-offspring pairs of horses with unknown parentage relationships., (© 2023 Japanese Society of Animal Science.)

The integrity of thoroughbreds is maintained under strict regulation involving DNA parentage testing, which is robust in a population with high genetic variability. The genetic variability of the thoroughbred population is possibly fluctuating because of selective breeding that has focused on adaptations for racing performance. To monitor genetic variability within the population and the effectiveness of short tandem repeat (STR) parentage testing, we investigated allele frequencies and the exclusion probability (PE) of 16-17 loci of a parentage panel in the Japanese thoroughbred population over 15 years. Expected heterozygosities (He) of 14 loci indicated a decreasing trend, and the average He of the population decreased significantly. Low genetic variability was possibly induced by a decrease in population size and a selective breeding bias. Four loci showed both a significant increase in allele frequency and a significant decrease in He; it is assumed that those loci were affected by positive selection for racing performance. There was a significant decrease in the PE because of the changes in genetic variability; however, it has remained over 0.99995. The current STR panel is still effective for parentage control, but it will be necessary to continuously monitor genetic variability, which has decreased over 15 years., (© 2018 Japanese Society of Animal Science.)