Thromboembolism after coronavirus disease 2019 vaccination in atrial fibrillation/flutter: a self-controlled case series study.

BACKGROUND AND AIMS: Concerns about the safety of coronavirus disease 2019 (COVID-19) vaccines in patients with atrial fibrillation/flutter (AF/AFL) have arisen due to reports of thrombo-embolic events following COVID-19 vaccination in the general population. This study aimed to evaluate the risk of thrombo-embolic events after COVID-19 vaccination in patients with AF/AFL. METHODS: This was a modified self-controlled case-series study using a comprehensive nationwide-linked database provided by the National Health Insurance Service in South Korea to calculate incidence rate ratios (IRRs) of thrombo-embolic events. The study population included individuals aged ≥12 years who were either vaccinated (e.g. one or two doses) or unvaccinated during the period from February to December 2021. The primary outcome was a composite of thrombo-embolic events, including ischaemic stroke, transient ischaemic attack, and systemic thromboembolism. The risk period was defined as 0-21 days following COVID-19 vaccination. RESULTS: The final analysis included 124 127 individuals with AF/AFL. The IRR of thrombo-embolic events within 21 days after COVID-19 vaccination, compared with that during the unexposed control period, was 0.93 [95% confidence interval (CI) 0.77-1.12]. No significant risk variations were noted by sex, age, or vaccine type. However, patients without anticoagulant therapy had an IRR of 1.88 (95% CI 1.39-2.54) following vaccination. CONCLUSIONS: In patients with AF/AFL, COVID-19 vaccination was generally not associated with an increased risk of thrombo-embolic events. However, careful individual risk assessment is required when advising vaccination for those not on oral anticoagulant, as these patients exhibited an increased risk of thrombo-embolic events post-vaccination.

Mildly Reduced Renal Function Is Associated With Increased Heart Failure Admissions in Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: The association between renal dysfunction and cardiovascular outcomes has yet to be determined in patients with hypertrophic cardiomyopathy (HCM). We aimed to investigate whether mildly reduced renal function is associated with the prognosis in patients with HCM. METHODS: Patients with HCM were enrolled at two tertiary HCM centers. Patients who were on dialysis, or had a previous history of heart failure (HF) or stroke were excluded. Patients were categorized into 3 groups by estimated glomerular filtration rate (eGFR): stage I (eGFR ≥ 90 mL/min/1.73 m², n = 538), stage II (eGFR 60-89 mL/min/1.73 m², n = 953), and stage III-V (eGFR < 60 mL/min/1.73 m², n = 265). Major adverse cardiovascular events (MACEs) were defined as a composite of cardiovascular death, hospitalization for HF (HHF), or stroke during median 4.0-year follow-up. Multivariable Cox regression model was used to adjust for covariates. RESULTS: Among 1,756 HCM patients (mean 61.0 ± 13.4 years; 68.1% men), patients with stage III-V renal function had a significantly higher risk of MACEs (adjusted hazard ratio [aHR], 2.71; 95% confidence interval [CI], 1.39-5.27; P = 0.003), which was largely driven by increased incidence of cardiovascular death and HHF compared to those with stage I renal function. Even in patients with stage II renal function, the risk of MACE (vs. stage I: aHR, 2.21' 95% CI, 1.23-3.96; P = 0.008) and HHF (vs. stage I: aHR, 2.62; 95% CI, 1.23-5.58; P = 0.012) was significantly increased. CONCLUSION: This real-world observation showed that even mildly reduced renal function (i.e., eGFR 60-89 mL/min/1.73 m²) in patients with HCM was associated with an increased risk of MACEs, especially for HHF.

Comparative cardiovascular outcomes in type 2 diabetes patients taking dapagliflozin versus empagliflozin: a nationwide population-based cohort study.

BACKGROUND: Sodium-glucose co-transporter-2 inhibitors displayed cardiovascular benefits in type 2 diabetes mellitus in previous studies; however, there were some heterogeneities regarding respective cardiovascular outcomes within the class. Furthermore, their efficacies in Asians, females, and those with low cardiovascular risks were under-represented. Thus, we compared the cardiovascular outcomes between new users of dapagliflozin and empagliflozin in a broad range of patients with type 2 diabetes mellitus using a nationwide population-based real-world cohort from Korea. METHODS: Korean National Health Insurance registry data between May 2016 and December 2018 were extracted, and an active-comparator new-user design was applied. The primary outcome was a composite of heart failure (HF)-related events (i.e., hospitalization for HF and HF-related death), myocardial infarction, ischemic stroke, and cardiovascular death. The secondary outcomes were individual components of the primary outcome. RESULTS: A total of 366,031 new users of dapagliflozin or empagliflozin were identified. After 1:1 nearest-neighbor propensity score matching, 72,752 individuals (mean age approximately 56 years, 42% women) from each group were included in the final analysis, with a follow-up of 150,000 ~ person-years. Approximately 40% of the patients included in the study had type 2 diabetes mellitus as their sole cardiovascular risk factor, with no other risk factors. The risk of the primary outcome was not different significantly between dapagliflozin and empagliflozin users (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.855-1.006). The risks of secondary outcomes were also similar, with the exception of the risks of HF-related events (HR 0.84, 95% CI 0.714-0.989) and cardiovascular death (HR 0.76, 95% CI 0.618-0.921), which were significantly lower in the dapagliflozin users. CONCLUSIONS: This large-scale nationwide population-based real-world cohort study revealed no significant difference in composite cardiovascular outcomes between new users of dapagliflozin and empagliflozin. However, dapagliflozin might be associated with lower risks of hospitalization or death due to HF and cardiovascular death than empagliflozin in Asian patients with type 2 diabetes mellitus.

Prognostic implications of left ventricular mass-geometry in patients with no or nonobstructive coronary artery disease.

BACKGROUND: Coronary computed tomography angiography (CCTA) is widely used as a first-line noninvasive modality that frequently exhibits no or nonobstructive coronary artery disease (CAD) in clinical practice, along with abnormal left ventricular (LV) geometry on echocardiography. However, the combined prognostic value of these findings has not been well elucidated. Therefore, we aimed to evaluate the prognostic implications of abnormal LV geometry in individuals with no or nonobstructive CAD. METHODS: A total of 5806 subjects with no CAD or nonobstructive CAD (luminal narrowing < 50%) on CCTA were included in the study. The major exclusion criteria were structural heart disease and a history of myocardial infarction or coronary revascularization. Abnormal LV geometry on echocardiography was defined as LV mass index > 95 g/m2 in women and > 115 g/m2 in men, and/or relative wall thickness > 0.42. The primary outcome was all-cause mortality. RESULTS: A total of 5803 subjects without significant obstructive CAD (age, 56.6 ± 8.87 years; men, 3884 [66.9%]). Of them, 4045 (69.7%) subjects had normal LV geometry and 1758 (30.3%) had abnormal LV geometry respectively. During a mean follow-up of 6.2 ± 1.48 years, 84 (1.44%) subjects died in the study population. Of these, 56 subjects were from the normal LV geometry group (1.24%) and 28 were from the abnormal LV geometry group (2.32%). Subjects with abnormal LV geometry had significantly worse survival rates (log-rank, p < 0.001). After adjustment for confounding factors, abnormal LV geometry was an independent predictor of all-cause mortality (adjusted hazard ratio, 1.64; 95% confidence interval, 1.04-2.58; p = 0.034). Moreover, abnormal LV geometry was significantly worse in survival when classified as those with no CAD (log-rank, p = 0.024) and nonobstructive CAD (Log-rank, p < 0.001). CONCLUSIONS: Abnormal LV geometry portends a worse prognosis in subjects with no or nonobstructive CAD. These findings suggest that LV geometry assessment can help improve the stratification of individuals with these CCTA findings.

Relationship between dominant frequency, organization index, and left atrial size in patients with atrial fibrillation.

INTRODUCTION: Frequency domain analysis is a methodology for quantifying the organization of atrial fibrillation (AF) pattern to understand the pathophysiology of the electrical mechanism. We aimed to investigate whether the dominant frequency (DF) and organization index (OI) can indicate left atrial (LA) dilatation in patients with AF. METHODS AND RESULTS: This observational, retrospective, single-center cohort study assessed 100 patients with persistent AF. The study population was divided into two groups based on an anterior-posterior LA dimension (LAD of 50 mm) measured by transthoracic echocardiography. The groups were one-to-one propensity score-matched. Frequency domain analysis was performed using signals at leads II and V1 on surface electrocardiogram to calculate the DF and OI. In all patients, the DF was shown to have an inverse relationship with LAD (R = -.369, p < .001 in lead II; R = -.330, p = .001 in lead V1), while the OI was directly associated with LAD (R = .234, p = .190 in lead II; R = .283, p = .004 in lead V1). However, no significant relationship between the signal amplitude and LAD was observed. Compared to patients with LAD ≤ 50 mm, those with LAD > 50 mm had a lower DF (5.057 ± 0.740 vs. 4.542 ± 0.898, p = .002) and higher OI (0.261 ± 0.104 vs. 0.322 ± 0.116, p = .007) in lead V1. These findings were consistent with those found in lead II. CONCLUSION: Patients with persistent AF and a larger LA size had a significantly higher OI and lower DF than those with a smaller LA size. Atrial electrical properties of structural remodeling are associated with increased organization of atrial signals.

Reconsidering the cut-off diastolic blood pressure for predicting cardiovascular events: a nationwide population-based study from Korea.

AIMS: It is unclear whether a J-curve association exists in cardiovascular risk prediction and how independently systolic and diastolic blood pressure (BP) predict cardiovascular outcomes. This study evaluated the association of systolic and diastolic BP with major cardiovascular events to clarify these issues. METHODS AND RESULTS: Antihypertensive medication-naïve subjects with available BP measurements and no history of cardiovascular events were extracted from the National Health Insurance Services Health Screening Cohort. The study endpoint was a composite of cardiac death, myocardial infarction, stroke, and heart failure. The study population comprised 290 600 subjects (median follow-up duration 6.7 years). The risk for major cardiovascular events was lowest at systolic and diastolic BPs of 90-99 mmHg and 40-49 mmHg, respectively, above which BPs demonstrated a log-linear risk prediction. Systolic and diastolic BPs were highly correlated. The risk prediction of diastolic BP was inconsistent when stratified by systolic BP. A wider pulse pressure rather than a higher diastolic BP was significantly associated with cardiovascular outcomes among men aged ≥55 years. In addition, the difference between diastolic BPs of <80 mmHg and 80-89 mmHg mostly disappeared after statistical adjustment or stratification. CONCLUSION: Elevated BP is a strong predictor of future cardiovascular events including cardiac death, myocardial infarction, stroke, and heart failure. This study showed that the log-linear relationship between BP and cardiovascular events extended down to a BP of ≥90/40 mmHg. Although hypertension is defined using a lower systolic BP cut-off of ≥130 mmHg, the diastolic BP component of ≥80 mmHg seems disproportionately low.

In Defense of the Commons: Young Children Negatively Evaluate and Sanction Free Riders.

Human flourishing depends on individuals paying costs to contribute to the common good, but such arrangements are vulnerable to free riding, in which individuals benefit from others' contributions without paying costs themselves. Systems of tracking and sanctioning free riders can stabilize cooperation, but the origin of such tendencies is not well understood. Here, we provide evidence that children as young as 4 years old negatively evaluate and sanction free riders. Across six studies, we showed that these tendencies are robust, large in magnitude, tuned to intentional rather than unintentional noncontribution, and generally consistent across third- and first-party cases. Further, these effects cannot be accounted for by factors that frequently co-occur with free riding, such as nonconforming behaviors or the costs that free riding imposes on the group. Our findings demonstrate that from early in life, children both hold and enforce a normative expectation that individuals are intrinsically obligated to contribute to the common good.

Oxaliplatin-induced acute tubulointerstitial nephritis: Two case reports
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Oxaliplatin is a platinum compound commonly used in the treatment of advanced colorectal cancer. This report describes two patients who had received repetitive combination chemotherapy including oxaliplatin for the treatment of metastatic colon cancer and who visited the emergency department with acute kidney injury several days after experiencing a hypersensitivity reaction to oxaliplatin. In both cases, the pathologic diagnosis was acute tubulointerstitial nephritis, and corticosteroid therapy resulted in improved renal function. Induction of acute tubulointerstitial nephritis by oxaliplatin has rarely been reported.
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How do 3-month-old infants attribute preferences to a human agent?

The current study showed that 3-month-old infants attributed a preference to a human agent, with her face and upper body visible, when she consistently reached for and grasped one of two objects with her bare hand. In contrast, infants did not appear to interpret the agent's same actions of grasping the object as indicative of her preference when it was the only object present or when it hid the other object from her but not from the infants. These results suggest that even from an early age, infants interpret human agents' actions in terms of mental states such as goals and preferences. In light of the current results, mechanisms for early psychological understanding are discussed.

Alpha-1,3-galactosyltransferase-deficient miniature pigs produced by serial cloning using neonatal skin fibroblasts with loss of heterozygosity.

OBJECTIVE: Production of alpha-1,3-galactosyltransferase (αGT)-deficient pigs is essential to overcome xenograft rejection in pig-to-human xenotransplantation. However, the production of such pigs requires a great deal of cost, time, and labor. Heterozygous αGT knockout pigs should be bred at least for two generations to ultimately obtain homozygote progenies. The present study was conducted to produce αGT-deficient miniature pigs in much reduced time using mitotic recombination in neonatal ear skin fibroblasts. METHODS: Miniature pig fibroblasts were transfected with αGT gene-targeting vector. Resulting gene-targeted fibroblasts were used for nuclear transfer (NT) to produce heterozygous αGT gene-targeted piglets. Fibroblasts isolated from ear skin biopsies of these piglets were cultured for 6 to 8 passages to induce loss of heterozygosity (LOH) and treated with biotin-conjugated IB4 that binds to galactose-α-1,3-galactose, an epitope produced by αGT. Using magnetic activated cell sorting, cells with monoallelic disruption of αGT were removed. Remaining cells with LOH carrying biallelic disruption of αGT were used for the second round NT to produce homozygous αGT gene-targeted piglets. RESULTS: Monoallelic mutation of αGT gene was confirmed by polymerase chain reaction in fibroblasts. Using these cells as nuclear donors, three heterozygous αGT gene-targeted piglets were produced by NT. Fibroblasts were collected from ear skin biopsies of these piglets, and homozygosity was induced by LOH. The second round NT using these fibroblasts resulted in production of three homozygous αGT knockout piglets. CONCLUSION: The present study demonstrates that the time required for the production of αGT-deficient miniature pigs could be reduced significantly by postnatal skin biopsies and subsequent selection of mitotic recombinants. Such procedure may be beneficial for the production of homozygote knockout animals, especially in species, such as pigs, that require a substantial length of time for breeding.

13-month-olds' understanding of social interactions.

In the present research, we investigated how 13-month-olds use their emergent theory-of-mind understanding (i.e., understanding about other people's mental states, such as their intentions, perceptions, and beliefs) and social-evaluation skills to make sense of social interactions. The infants watched three puppets (A, B, and C) interact. The results showed that after seeing Agents A and B interact in a positive manner, infants expected them to continue doing so, even after they saw B hit another agent, C, while A was absent. When A was present to witness B's harmful action, however, infants expected A to change his or her behavior and ignore B. Therefore, infants seemed to consider A's perspectives when predicting A's actions. Furthermore, if B accidentally hit C when A was present, infants seemed to accept that A could interact or not interact with B, which suggests that they had taken into account B's intention in their interpretations of the agents' interactions.

Targeted disruption of Ataxia-telangiectasia mutated gene in miniature pigs by somatic cell nuclear transfer.

Ataxia telangiectasia (A-T) is a recessive autosomal disorder associated with pleiotropic phenotypes, including progressive cerebellar degeneration, gonad atrophy, and growth retardation. Even though A-T is known to be caused by the mutations in the Ataxia telangiectasia mutated (ATM) gene, the correlation between abnormal cellular physiology caused by ATM mutations and the multiple symptoms of A-T disease has not been clearly determined. None of the existing ATM mouse models properly reflects the extent to which neurological degeneration occurs in human. In an attempt to provide a large animal model for A-T, we produced gene-targeted pigs with mutations in the ATM gene by somatic cell nuclear transfer. The disrupted allele in the ATM gene of cloned piglets was confirmed via PCR and Southern blot analysis. The ATM gene-targeted pigs generated in the present study may provide an alternative to the current mouse model for the study of mechanisms underlying A-T disorder and for the development of new therapies.

Differing Efficacy of Dapagliflozin Versus Empagliflozin on the Risk of Incident Atrial Fibrillation in Patients With Type 2 Diabetes: A Real-World Observation Using a Nationwide, Population-Based Cohort.

BACKGROUND: Meta-analyses of large clinical trials investigating SGLT2 (sodium-glucose cotransporter-2) inhibitors have suggested their protective effects against atrial fibrillation in patients with type 2 diabetes. However, the results were predominantly driven from trials involving dapagliflozin. METHODS AND RESULTS: We used a nationwide, population-based cohort of patients with type 2 diabetes who initiated either dapagliflozin or empagliflozin between May 2016 and December 2018. An active-comparator, new-user design was used, and the 2 groups of patients were matched using propensity scores. The primary outcome was incident nonvalvular atrial fibrillation, which was analyzed using both the main intention-to-treat and sensitivity analysis that censored patients who skipped their medications for ≥30 days. Men ≥55 years of age and women ≥60 years of age with ≥1 traditional risk factor or those with established cardiovascular disease were categorized as high cardiovascular risk group. Patients not included in the high-risk group were categorized as low risk. After 1:1 propensity-score matching, a total of 137 928 patients (mean age, 55 years; 58% men) were included and followed up for 2.2±0.6 years. The risk of incident atrial fibrillation was significantly lower in the dapagliflozin group in both the main (hazard ratio [HR], 0.885 [95% CI, 0.789-0.992]) and sensitivity analyses (HR, 0.835 [95% CI, 0.719-0.970]). Notably, this was consistent in both the low and high cardiovascular risk groups. There was no effect modification by age, sex, body mass index, duration of diabetes, or renal function. CONCLUSIONS: This real-world, population-based study demonstrates that patients with type 2 diabetes using dapagliflozin may have a lower risk of developing nonvalvular atrial fibrillation than those using empagliflozin.

Mitral Annular Tissue Velocity Predicts Survival in Patients With Primary Mitral Regurgitation.

BACKGROUND AND OBJECTIVES: Early diastolic mitral annular tissue (e') velocity is a commonly used marker of left ventricular (LV) diastolic function. This study aimed to investigate the prognostic implications of e' velocity in patients with mitral regurgitation (MR). METHODS: This retrospective cohort study included 1,536 consecutive patients aged <65 years with moderate or severe chronic primary MR diagnosed between 2009 and 2018. The primary and secondary outcomes were all-cause and cardiovascular mortality, respectively. According to the current guidelines, the cut-off value of e' velocity was defined as 7 cm/s. RESULTS: A total of 404 individuals were enrolled (median age, 51.0 years; 64.1% male; 47.8% severe MR). During a median 6.0-year follow-up, there were 40 all-cause mortality and 16 cardiovascular deaths. Multivariate analysis revealed a significant association between e' velocity and all-cause death (adjusted hazard ratio [aHR], 0.770; 95% confidence interval [CI], 0.634-0.935; p=0.008) and cardiovascular death (aHR, 0.690; 95% CI, 0.477-0.998; p=0.049). Abnormal e' velocity (≤7 cm/s) independently predicted all-cause death (aHR, 2.467; 95% CI, 1.170-5.200; p=0.018) and cardiovascular death (aHR, 5.021; 95% CI, 1.189-21.211; p=0.028), regardless of symptoms, LV dimension and ejection fraction. Subgroup analysis according to sex, MR severity, mitral valve replacement/repair, and symptoms, showed no significant interactions. Including e' velocity in the 10-year risk score improved reclassification for mortality (net reclassification improvement [NRI], 0.154; 95% CI, 0.308-0.910; p<0.001) and cardiovascular death (NRI, 1.018; 95% CI, 0.680-1.356; p<0.001). CONCLUSIONS: In patients aged <65 years with primary MR, e' velocity served as an independent predictor of all-cause and cardiovascular deaths.

Assessing lung fluid status using noninvasive bioelectrical impedance analysis in patients with acute heart failure: A pilot study.

BACKGROUND: Outpatient monitoring of pulmonary congestion in heart failure (HF) patients may reduce hospitalization rates. This study tested the feasibility of non-invasive high-frequency bioelectrical impedance analysis (HF-BIA) for estimating lung fluid status. METHODS: This prospective study included 70 participants: 50 with acute HF (HF group) and 20 without HF (control group). All participants underwent a supine chest CT scan to measure lung fluid content with lung density analysis software. Concurrently, direct segmental multi-frequency BIA was performed to assess the edema index (EI) of the trunk, entire body, and extremities. RESULTS: The correlation coefficients between lung fluid content and EI measured using HF-BIA were r = 0.566 (p < 0.001) and r = 0.550 (p < 0.001) for the trunk and whole body, respectively. In the HF group, the trunk EI (0.402 ± 0.015) and whole body EI (0.402 ± 0.016) were significantly higher than those of the control group (trunk EI, 0.383 ± 0.007; whole body EI, 0.383 ± 0.007; all p < 0.001). The lung fluid content was significantly higher in the HF than that in the control group (23.7 ± 5.3 vs. 15.5 ± 2.8%, p < 0.001). The log value of NT pro-BNP was significantly correlated with trunk EI (r = 0.688, p < 0.001) and whole-body EI (r = 0.675, p < 0.001) measured by HF-BIA, and the lung fluid content analyzed by CT (r = 0.686, p < 0.001). CONCLUSIONS: BIA-based EI measurements of the trunk and whole body significantly correlated with lung fluid content and NT pro-BNP levels. Non-invasive BIA could be a promising screening tool for lung fluid status monitoring in acute HF patients.

Central Facial Nervous System Biomolecules Involved in Peripheral Facial Nerve Injury Responses and Potential Therapeutic Strategies.

Peripheral facial nerve injury leads to changes in the expression of various neuroactive substances that affect nerve cell damage, survival, growth, and regeneration. In the case of peripheral facial nerve damage, the injury directly affects the peripheral nerves and induces changes in the central nervous system (CNS) through various factors, but the substances involved in these changes in the CNS are not well understood. The objective of this review is to investigate the biomolecules involved in peripheral facial nerve damage so as to gain insight into the mechanisms and limitations of targeting the CNS after such damage and identify potential facial nerve treatment strategies. To this end, we searched PubMed using keywords and exclusion criteria and selected 29 eligible experimental studies. Our analysis summarizes basic experimental studies on changes in the CNS following peripheral facial nerve damage, focusing on biomolecules that increase or decrease in the CNS and/or those involved in the damage, and reviews various approaches for treating facial nerve injury. By establishing the biomolecules in the CNS that change after peripheral nerve damage, we can expect to identify factors that play an important role in functional recovery from facial nerve damage. Accordingly, this review could represent a significant step toward developing treatment strategies for peripheral facial palsy.

Association between cardiac arrhythmia before pregnancy and gestational diabetes: a nationwide population-based study in Korea.

Given the higher prevalence of cardiac arrhythmias in individuals with diabetes, we investigated the relationship between cardiac arrhythmias and the incidence of gestational diabetes (GDM). This retrospective cohort study utilized data from the Korean Health Insurance Service database, encompassing 1,113,729 women who gave birth between January 2007 and December 2015. After excluding those who did not undergo National Health Screening tests within 1 year prior to pregnancy, those with multifetal pregnancies, and those diagnosed with diabetes, we analyzed 365,880 singleton pregnancies without a history of diabetes. Of these, 3,253 (0.9%) had cardiac arrhythmias, including premature extra beats, supraventricular tachyarrhythmias, and/or atrial flutter/fibrillation. GDM occurred in 31,938 (8.7%) subjects during pregnancy, and was more prevalent in women with cardiac arrhythmia than in those without (14.9% vs. 8.7%, p<0.001). In the multivariate analysis, the association between cardiac arrhythmia and GDM remained statistically significant (adjusted odds ratio, 1.78; 95% CI, 1.615-1.970; p<0.001). Subgroup analysis revealed that the risk of GDM was consistently statistically significant in subjects with cardiac arrhythmia, regardless of age, body mass index, and the presence or absence of chronic hypertension. Therefore, cardiac arrhythmias before and during pregnancy appear to be associated with an increased risk of developing GDM.

Left atrial reservoir strain as a novel predictor of new-onset atrial fibrillation in light-chain-type cardiac amyloidosis.

AIMS: To investigate whether left arterial reservoir strain (LASr) could predict new-onset atrial fibrillation (NOAF) in patients with light-chain-type cardiac amyloidosis (ALCA). METHODS AND RESULTS: This study enrolled 427 patients with CA from two tertiary centres between 2005 and 2019. LASr was measured using a vendor-independent analysis programme. The primary outcome was NOAF. A total of 287 patients with ALCA were included [median age 63.0 (56.0-70.0) years, 53.3% male]. The median LASr was 13.9% (10.5-20.8%). During the median follow-up of 0.85 years, AF occurred in 34 patients (11.8%). In the receiver operating characteristics curve analysis, the optimal cut-off of LASr for predicting NOAF was 14.4%. Patients with LASr ≤14.4% had a higher risk of NOAF than those with LASr >14.4% (18.1% vs. 5.1%, P < 0.010). In the multivariate analysis adjusting for confounding factors, including left arterial volume index and left ventricular global longitudinal strain (LV-GLS), higher LASr (%) was independently associated with lower risk for NOAF [adjusted hazard ratio (aHR): 0.936, 95% confidence interval (95% CI): 0.879-0.997, P = 0.039]. Furthermore, LASr ≤14.4% was an independent predictor for NOAF (aHR: 3.370, 95% CI: 1.337-8.492, P = 0.010). This remained true after accounting for all-cause death as a competing risk. Compared with Model 1 (LV-GLS) and Model 2 (LV-GLS plus LAVI), Model 3, including LASr showed a better reclassification ability for predicting NOAF (net reclassification index = 0.735, P < 0.001 compared with Model 1; net reclassification index = 0.514, P = 0.003 compared with Model 2). CONCLUSION: LASr was an independent predictor of NOAF in patients with ALCA.

Prognosis of patients with hypertrophic cardiomyopathy and low-normal left ventricular ejection fraction.

OBJECTIVE: To investigate whether low-normal left ventricular ejection fraction (LVEF) is associated with adverse outcomes in hypertrophic cardiomyopathy (HCM) and evaluate the incremental value of predictive power of LVEF in the conventional HCM sudden cardiac death (SCD)-risk model. METHODS: This retrospective study included 1858 patients with HCM from two tertiary hospitals between 2008 and 2019. We classified LVEF into three categories: preserved (≥60%), low normal (50%-60%) and reduced (<50%); there were 1399, 415, and 44 patients with preserved, low-normal, and reduced LVEF, respectively. The primary outcome was a composite of SCD, ventricular tachycardia/fibrillation and appropriate implantable cardioverter-defibrillator shocks. Secondary outcomes were hospitalisation for heart failure (HHF), cardiovascular death and all-cause death. RESULTS: During the median follow-up of 4.09 years, the primary outcomes occurred in 1.9%. HHF, cardiovascular death, and all-cause death occurred in 3.3%, 1.9%, and 5.3%, respectively. Reduced LVEF was an independent predictor of SCD/equivalent events (adjusted HR (aHR) 5.214, 95% CI 1.574 to 17.274, p=0.007), adding predictive value to the HCM risk-SCD model (net reclassification improvement 0.625). Compared with patients with HCM with preserved LVEF, those with low-normal and reduced LVEF had a higher risk of HHF (LVEF 50%-60%, aHR 2.457, 95% CI 1.423 to 4.241, p=0.001; LVEF <50%, aHR 7.937, 95% CI 3.315 to 19.002, p<0.001) and cardiovascular death (LVEF 50%-60%, aHR 2.641, 95% CI 1.314 to 5.309, p=0.006; LVEF <50%, aHR 5.405, 95% CI 1.530 to 19.092, p=0.009), whereas there was no significant association with all-cause death. CONCLUSIONS: Low-normal LVEF was an independent predictor of HHF and cardiovascular death in patients with HCM.