Atrial fibrillation detection using ambulatory smartwatch photoplethysmography and validation with simultaneous holter recording.

BACKGROUND: Atrial fibrillation (AF)-associated embolic stroke is preventable, and AF detection may help to prevent stroke in subjects with paroxysmal AF. We aimed to evaluate the AF detection performance of smartwatch photoplethysmography (PPG) and the feasibility of ambulatory monitoring for AF detection in the daily life. DESIGN AND METHODS: Consecutive subjects who underwent ambulatory Holter electrocardiogram (ECG) monitoring for AF detection or AF burden evaluation were enrolled. The participants underwent 24 hours of simultaneous Holter ECG monitoring and continuous PPG recording using a Garmin smartwatch. The PPG signals were processed for noise rejection, beat detection, beat labeling, and rhythm labeling for each 5-minute segment. The accuracy of the PPG AF detection was calculated using the corresponding simultaneous Holter ECG as the AF diagnostic standard. RESULTS: Among the 200 available participants, 112 participants (56%) developed AF (the AF group). The sensitivity, specificity, and positive predicted value of AF detection in participants were 97.3%, 88.6%, and 91.6%, respectively. The area under the receiver operating characteristic curve was 0.90. When the performance was analyzed in these 5-minute segments, the sensitivity, specificity, and positive predicted values of AF detection were 97.1%, 86.8%, and 89.7%, respectively. CONCLUSIONS: This study demonstrated the feasibility of ambulatory monitoring for AF detection using a commercial smartwatch in daily life. A smartwatch may be an alternative screening tool to standard ambulatory Holter monitoring.

Deficiency of circadian gene cryptochromes in bone marrow-derived cells protects against atherosclerosis in LDLR-/- mice.

Cryptochromes are photoreceptors that mediate the circadian entrainment by light in plants and animals. They are also involved in magnetic field sensing in some animals. Recent studies suggest that cryptochromes play an essential role in metabolism and cardiovascular disease. However, the tissue-specific function of cryptochromes in atherosclerosis is unknown. We transplanted bone marrow from wild-type (WT) and cryptochrome 1/2 knockout (Cry1/2 KO) mice into irradiated recipient low-density lipoprotein receptor knockout (LDLR-/- ) mice and induced atherosclerosis with a high cholesterol diet for 12 weeks. There was a reduction in atherosclerotic plaques and macrophage accumulation in the aorta of LDLR-/- mice that received Cry1/2 KO bone marrow compared to mice that received WT bone marrow. Bone marrow-derived macrophages (BMDMs) from Cry1/2 KO mice exhibited impaired uptake of low-density lipoprotein, and subsequently, impaired foam cell formation. Analysis of macrophage mRNA circadian oscillations revealed that the circadian rhythm of the LDLR mRNAs was lost in Cry1/2 KO BMDMs. Reinstalling the circadian oscillatory LDLR mRNAs using adenovirus into the BMDMs was able to rescue the lipid uptake and foam cell formation function. However, the noncircadian oscillatory LDLR mRNAs exhibited reduced ability to rescue the macrophage functions. These findings indicate that cryptochromes in bone marrow-derived cells are critical mediators of atherosclerosis through regulation of the LDLR mRNA circadian rhythm. Therapeutic measures targeting cryptochromes in the macrophage may have important implications for atherosclerosis.

Risk of major bleeding associated with concomitant use of anticancer drugs and direct oral anticoagulant in patients with cancer and atrial fibrillation.

This study evaluated the risk of major bleeding associated with concomitant use of direct oral anticoagulant (DOAC) and anticancer drugs (ACDs), which share metabolic pathways, in patients with atrial fibrillation (AF) and cancer. We performed a retrospective cohort study using Taiwan's National Health Insurance database and included patients with AF and cancer who received DOAC prescriptions from 1 to 2012 to 31 December 2017. The incidence of major bleeding in person-quarters with concomitant use of DOAC and any of 15 ACDs with inhibitory or competitive effects of CYP3A4 or P-gp activity (docetaxel, vinorelbine, methotrexate, irinotecan, etoposide, doxorubicin, cyclophosphamide, imatinib, nilotinib, abiraterone, bicalutamide, tamoxifen, anastrozole, cyclosporine, tacrolimus) was compared with that in person-quarters with DOAC alone. Adjusted incidence-rate differences between DOAC use with and without concurrent ACDs were estimated using Poisson regression models weighted by the inverse probability of treatment. In 13,158 patients with AF and cancer (76.9 ± 8.9 years; male 60%), 1545 major bleeding events occurred during 90,540 DOAC-exposed person-quarters. Concurrent use of DOAC and any of 15 ACDs occurred in only 18% of patients. Compared with use of DOAC alone, concomitant use of DOAC and these ACDs was not associated with an increased risk of major bleeding. Co-medication with DOAC and ACDs with inhibitory or competitive effects on CYP3A4 or P-gp activity was not associated with a higher risk of major bleeding than DOAC alone. Our findings may provide clinicians with confidence regarding the safety of concurrent use of DOAC and ACDs in patients with AF and cancer.

The Efficacy and Safety of Short-Term Tolvaptan Usage in Patients with Acute Decompensated Heart Failure.

Background: Patients admitted with acute decompensated heart failure (ADHF) have a poor prognosis and poor quality of life due to dyspnea and edema. Tolvaptan, a vasopressin V2 receptor antagonist, is an effective water diuretic. This study aimed to evaluate the efficacy and safety of a short course of tolvaptan to treat volume overload in patients with ADHF. Methods: We conducted a phase III, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of a short course of tolvaptan (15 mg/day for 4 days) in hospitalized ADHF patients with volume overload despite the use of conventional diuretics. The primary end-point was the change in body weight after 4 days of treatment. The secondary end-points were the change in intake/output balance, change in serum sodium/potassium concentrations, physician/patient assessed signs and symptoms of heart failure after 4 days of treatment, and all-cause mortality in 1 month. Results: A total of 110 patients were screened, and 91 were randomized to receive 15 mg/day of tolvaptan for 4 days (n = 46) or matching placebo (n = 45). Compared to the placebo-treated patients, tolvaptan significantly reduced body weight (-1.36 ± 2.13 kg in the tolvaptan group vs. -0.59 ± 1.27 kg in the placebo group, p = 0.0394). The tolvaptan group also had a negative intake/urine volume balance compared to the placebo group (-509.3 ± 2788.2 ml vs. 975.5 ± 1903.1 ml, p = 0.0059). The safety profile of tolvaptan was acceptable. Conclusions: Tolvaptan significantly reduced volume overload in hospitalized ADHF patients with volume overload despite the use of conventional diuretics.

Incidence and consequences of resuming oral anticoagulant therapy following hematuria and risks of ischemic stroke and major bleeding in patients with atrial fibrillation.

Following hematuria, it is uncertain to what extent a vitamin K antagonist (VKA) or non-VKA oral anticoagulant (NOAC) is resumed, and the risks of ischemic stroke/systemic embolism and major bleeding associated with NOAC and VKA resumption are unknown. A cohort study was conducted using electronic medical records collected from 2009 to 2017 at a multicenter healthcare provider in Taiwan. The cohort included 4155 atrial fibrillation patients receiving anticoagulant therapy with hematuria (age: 71.4 ± 11.2 years; 48.8% female). Within 90 days following hematuria, 3287 patients (79.1%) resumed oral anticoagulants including VKA (n = 1554, 37.4%) and NOACs (n = 1733, 41.7%), whereas 868 patients did not resume anticoagulant. Follow-up was initiated 90 days after the occurrence of hematuria, and time-varying multiple Cox regression analyses were used for comparisons between the resumption of NOAC and VKA. The event rates per 100 person-years in the VKA resumption and NOAC resumption groups were 3.04 and 3.28 for ischemic stroke/systemic embolism, and 2.63 and 2.92 for major bleeding, respectively. Patients resuming NOAC had similar risks of ischemic stroke/systemic embolism (hazard ratio 1.14, 95% CI 0.75-1.74) and major bleeding (hazard ratio 1.12, 95% CI 0.72-1.74) compared with those resuming VKA. Since 2011, the proportion of NOAC resumption has increased, whereas the proportions of VKA resumption and non-resumption have decreased. In conclusion, more and more patients who suffer a hematuria while on oral anticoagulant therapy resume NOAC. Patients resuming NOAC have similar risks of ischemic stroke/systemic embolism and major bleeding compared with those resuming VKA.

P wave duration ≥150 ms predicts poor left atrial function and ablation outcomes in non-paroxysmal atrial fibrillation.

BACKGROUND: It remains unknown whether P wave duration (PWD) ≥ 150 ms measured after extensive radiofrequency catheter ablation (RFCA) can identify non-paroxysmal atrial fibrillation (non-PAF) patients at increased risk of atrial tachyarrhythmia recurrence. We investigated the predicting power of PWD and its association with left atrial (LA) reverse remodeling in patients with non-PAF undergoing pulmonary vein isolation with LA linear ablation. METHODS: We retrospectively evaluated 136 patients who underwent RFCA for drug-refractory non-PAF. Electroanatomic mapping was acquired during AF. Low-voltage area (LVA) was defined as an area with bipolar voltage ≤0.5 mV. Electrocardiography and echocardiography were performed during sinus rhythm 1 day and 3 months after RFCA. PWD was measured using amplified 12­lead electrocardiography. Prolonged PWD was defined as maximum PWD ≥ 150 ms. RESULTS: Over a mean follow-up duration of 48 ± 35 months, 28 patients experienced atrial tachyarrhythmia recurrence. PWD was positively correlated with LVA (r = 0.527, p < 0.001) and inversely correlated with LA emptying fraction (r = -0.399, p < 0.001). PWD was shortened and LA emptying fraction (LAEF) was increased in patients without atrial tachyarrhythmia recurrence during follow-up. Atrial tachyarrhythmia-free survival was significantly more likely in patients without a prolonged PWD (83.5% vs 60.7%, p = 0.002). Multivariate analysis showed that LAEF and PWD were independent predictors of atrial tachyarrhythmia recurrence. CONCLUSIONS: PWD ≥ 150 ms measured after RFCA can identify patients with non-PAF at increased risk of atrial tachyarrhythmia recurrence. PWD is correlated with LVA and LAEF and reflects LA reverse remodeling.

Resuscitation outcomes of a wireless ECG telemonitoring system for cardiovascular ward patients experiencing in-hospital cardiac arrest.

BACKGROUND/PURPOSE: In-hospital cardiac arrest is a serious issue for hospitalized patients. The documented initial rhythm and detected medical events have been reported to influence the survival of cardiopulmonary resuscitation. This study aimed to identify the effect of continuous real-time electrocardiogram (ECG) monitoring on the prognosis of resuscitated patients in a general cardiac ward. METHODS: We conducted this retrospective study using medical records of hospitalized patients in a cardiovascular ward who experienced an in-hospital cardiac arrest and received cardiopulmonary resuscitation from February 2015 to December 2018. The patients who were considered to be at high risk of cardiac events such as ventricular arrhythmia would receive continuous ECG monitoring. A wireless ECG telemonitoring system was introduced to replace traditional bedside ECG monitors. The outcome measures were the initial success of resuscitation, 24-h survival after resuscitation, and survival to discharge. RESULTS: We enrolled 115 patients with a cardiac arrest during hospitalization, of whom 73 (63%) patients received wireless ECG telemonitoring. Patients receiving continuous ECG monitoring were associated with higher opportunities of initial success of resuscitation and 24-h survival after resuscitation (67.1% vs. 40.5%, p = 0.005; and 49.3% vs. 26.2%, p = 0.015, respectively) when comparing to the non-monitoring group; but no significant difference in survival to discharge (21.9% vs. 16.7%, p = 0.498) was observed. With adjustment of the covariates, the monitoring group was associated with a higher likelihood to reach the initial success of resuscitation (odds ratios [ORs], 3.21; 95% confidence interval [CI], 1.03-9.98). However, the effect of monitoring on 24-h survival and survival to discharge was close to null after adjusting for covariates. CONCLUSION: A wireless ECG telemonitoring system were beneficial to the initial success of resuscitation for patients at high risk of cardiovascular events suffering an in-hospital cardiac arrest; but had less impact on 24-h survival and survival to discharge.

Regulation of autophagy in leukocytes through RNA N6-adenosine methylation in chronic kidney disease patients.

Patients with chronic kidney diseases have multiple cellular dysfunctions leading to increased atherosclerosis, impaired immunity, and disturbed metabolism. However, it is unclear what is the fundamental signaling served as a marker or as a mediator for the dysregulated function in their leukocytes or tissues. Here we hypothesized that the N6-Methyladenosine (m6A) modification of the RNA in the leukocytes is responsible for the cellular dysfunction in chronic kidney diseases. Patients with chronic kidney diseases had significantly less m6A abundances in leukocytes and elevated RNA demethylase FTO proteins. The uremic toxin, indoxyl sulfate, activated the autophagy flux through modulation of FTO and m6A modifications in RNA. Notably, knockdown of FTO or inhibit the m6A by 3-deazaadenosine blocks the effects of indoxyl sulfate on autophagy activation in cells. These findings provide new insights into the mechanisms underlying chronic kidney disease-associated cellular dysfunction. Targeting RNA m6A modification may be a novel strategy for the treatment of chronic kidney diseases and autophagy.

Sacubitril/Valsartan Therapy Ameliorates Ventricular Tachyarrhythmia Inducibility in a Rabbit Myocardial Infarction Model.

BACKGROUND: Coronary artery disease is the most common cause of heart failure (HF) in developed countries. The aim of this study was to elucidate the mechanisms of reduction of arrhythmias after sacubitril/valsartan (LCZ696) therapy in a myocardial infarction (MI)-HF rabbit model. METHODS AND RESULTS: Chronic MI in rabbits with HF were divided into 3 groups: placebo control, valsartan 30 mg/day and LCZ696 60 mg/day. After 4 weeks of therapy, an electrophysiologic study and a dual voltage-calcium optical mapping study were performed. The LCZ696 group had significantly better left ventricular ejection fraction and lower ventricular tachyarrhythmia inducibility than the valsartan and placebo groups. The most common ventricular tachyarrhythmia pattern was 1 or 2 ectopic beats originating from the peri-infarct areas, followed by re-entrant beats surrounding phase singularity points. Compared to the valsartan and placebo groups, the LCZ696 group had significantly shorter action-potential duration, shorter intracellular calcium tau constant, faster conduction velocity, and shorter pacing cycle length to induce arrhythmogenic alternans. LCZ696 therapy reduced the phosphorylated calmodulin-dependent protein kinase II (CaMKII-p) expression. CONCLUSIONS: In a rabbit model with chronic MI and HF, LCZ696 therapy ameliorated postinfarct heart function impairment and electrophysiologic remodeling and altered CaMKII-p expression, leading to reduced ventricular tachyarrhythmia inducibility.

Angiographic Complete versus Clinical Selective Incomplete Percutaneous Revascularization in Heart Failure Patients with Multivessel Coronary Disease.

BACKGROUND: Patients with multivessel disease (MVD) often pursue complete revascularization (CR) during percutaneous coronary intervention (PCI) to improve prognosis. However, angiographic CR is not always feasible and is associated with some procedure-related complications in heart failure (HF) patients with MVD. Clinical selective incomplete revascularization (IR) may be reasonable for these high-risk patients, but its role in long-term outcomes remains uncertain. METHODS: Six hundred patients with HF and MVD submitted to PCI were enrolled. Major adverse cardiac events (MACEs) were defined as a composite of recurrent myocardial infarction, any revascularization, and all-cause mortality at 5 years. RESULTS: During a mean follow-up period of 3.7 ± 1.9 years, there was no significant difference in 5-year MACEs between selective IR and successful angiographic CR in HF patients with MVD. However, patients who failed CR had a significantly greater incidence of 5-year MACEs than those in the other two groups (failed CR: 46.4% vs. selective IR: 27.7% vs. successful CR: 27.8%, p < 0.001). CONCLUSIONS: Long-term outcomes of selective IR were comparable with those of successful angiographic CR in HF patients with MVD. However, patients that failed CR showed 2.53-fold increased risk of MACEs compared to patients undergoing either selective IR or successful angiographic CR. A more comprehensive planning strategy should be devised before PCI in HF patients with MVD.

Single Bolus Rosuvastatin Accelerates Calcium Uptake and Attenuates Conduction Inhomogeneity in Failing Rabbit Hearts With Regional Ischemia-Reperfusion Injury.

Acute statin therapy reduces myocardial ischemia/reperfusion (IR) injury-induced ventricular fibrillation (VF), but the underlying electrophysiological mechanisms remain unclear. This study sought to investigate the antiarrhythmic effects of a single bolus rosuvastatin injection in failing rabbit hearts with IR injury and to unveil the underlying molecular mechanisms. Rabbits were divided into rosuvastatin, rosuvastatin + L-NAME, control, and L-NAME groups. Intravenous bolus rosuvastatin (0.5 mg/kg) and/or L-NAME (10 mg/kg) injections were administered 1 hour and 15 minutes before surgery, respectively. Heart failure was induced using rapid ventricular pacing. Under general anesthesia with isoflurane, an IR model was created by coronary artery ligation for 30 minutes, followed by reperfusion for 15 minutes. Plasma NO end product levels were measured during IR. Then, hearts were excised and Langendorff-perfused for optical mapping studies. Cardiac tissues were sampled for Western blot analysis. Rosuvastatin increased plasma NO levels during IR, which was abrogated by L-NAME. Spontaneous VF during IR was suppressed by rosuvastatin (P < 0.001). Intracellular calcium (Cai) decay and conduction velocity were significantly slower in the IR zone. Rosuvastatin accelerated Cai decay, ameliorated conduction inhomogeneity, and reduced the inducibility of spatially discordant alternans and VF significantly. Western blots revealed significantly higher expression of enhancing endothelial NO-synthase and phosphorylated enhancing endothelial NO-synthase proteins in the Rosuvastatin group. Furthermore, SERCA2a, phosphorylated connexin43, and phosphorylated phospholamban were downregulated in the IR zone, which was attenuated or reversed by rosuvastatin. Acute rosuvastatin therapy before ischemia reduced IR-induced VF by improving SERCA2a function and ameliorating conduction disturbance in the IR zone.

The role of Asprosin in patients with dilated cardiomyopathy.

BACKGROUND: Asprosin is a novel fasting glucogenic adipokine discovered in 2016. Asprosin induces rapid glucose releases from the liver. However, its molecular mechanisms and function are still unclear. Adaptation of energy substrates from fatty acid to glucose is recently considered a novel therapeutic target in heart failure treatment. We hypothesized that the asprosin is able to modulate cardiac mitochondrial functions and has important prognostic implications in dilated cardiomyopathy (DCM) patients. METHODS: We prospectively enrolled 50 patients (86% male, mean age 55 ± 13 years) with DCM and followed their 5-year major adverse cardiovascular events from 2012 to 2017. Comparing with healthy individuals, DCM patients had higher asprosin levels (191.2 versus 79.7 ng/mL, P < 0.01). RESULTS: During the 5-year follow-up in the study cohort, 16 (32.0%) patients experienced adverse cardiovascular events. Patients with lower asprosin levels (< 210 ng/mL) were associated with increased risks of adverse clinical outcomes with a hazard ratio of 7.94 (95% CI 1.88-33.50, P = 0.005) when compared patients with higher asprosin levels (≥ 210 ng/mL). Using cardiomyoblasts as a cellular model, we showed that asprosin prevented hypoxia-induced cell death and enhanced mitochondrial respiration and proton leak under hypoxia. CONCLUSIONS: In patients with DCM, elevated plasma asprosin levels are associated with less adverse cardiovascular events in five years. The underlying protective mechanisms of asprosin may be linked to its functions relating to enhanced mitochondrial respiration under hypoxia.

Core-shell insulin-loaded nanofibrous scaffolds for repairing diabetic wounds.

Patients with diabetes mellitus have up to a 15% lifetime risk of non-healing and poorly healing wounds. This work develops core-shell nanofibrous bioactive insulin-loaded poly-D-L-lactide-glycolide (PLGA) scaffolds that release insulin in a sustained manner for repairing wounds in diabetic rats. To prepare the biodegradable core-shell nanofibers, PLGA and insulin solutions were fed into two capillary tubes of different sizes that were coaxially electrospun using two independent pumps. The scaffolds sustainably released insulin for four weeks. The hydrophilicity and water-containing capacity of core-shell nanofibrous insulin/PLGA scaffolds significantly exceeded those of blended nanofibrous scaffolds. The nanofibrous core-shell insulin-loaded scaffold reduced the amount of type I collagen in vitro, increased the transforming growth factor-beta content in vivo, and promoted diabetic would repair. The core-shell insulin-loaded nanofibrous scaffolds prolong the release of insulin and promote diabetic wound healing.

Observational study of dronedarone in Taiwanese patients with atrial fibrillation.

BACKGROUND/PURPOSE: Currently, data on the real-world use of dronedarone, an antiarrhythmic drug for atrial fibrillation (AF), are contradictory and often based on patient populations comprised of Caucasians. We prospectively investigated the efficacy and safety of dronedarone and risk factors related to treatment outcomes in a real-world use setting. METHODS: The prospective, observational, single-arm, multi-center study included a total of 824 Taiwanese patients with a diagnosis of paroxysmal or persistent AF and receiving dronedarone treatment. Risk factors analysis, efficacy, and safety of dronedarone were assessed with a follow-up of six months. RESULTS: Of the 824 patients enrolled (mean age, 75.3 ± 7.2 years), 95.2% had at least one cardiovascular risk factor. An increase in the proportion of patients with sinus rhythm following treatment was seen (52.1% at baseline vs. 67.4% at 6 months). A decrease in the mean duration of AF episodes (388.4 min vs. 62.3 min) and an increase in total AFEQT (65.4 ± 16.2 vs. 74.0 ± 11.8) were also observed after 6 months of treatment. Females, those under the age of 75, and those with symptomatic AF had higher odds of treatment success. At 6 months, 10.5% of patients reported treatment-related AEs. However, only 0.2% of the AEs were both severe in nature and causally related to dronedarone. CONCLUSION: This six-month study showed dronedarone to be relatively safe and efficacious and to improve quality-of-life in Taiwanese patients with atrial fibrillation. Odds of treatment success were related to the patient's gender, age, and AF type.

Incidence and Time Course of Symptomatic Paroxysmal Supraventricular Tachycardia During Pregnancy: A Nation-Wide Database Study.

BACKGROUND: Paroxysmal supraventricular tachycardia (PSVT) is a common arrhythmia. However, its incidence and time course in pregnant women are unclear. This study was conducted to determine the incidence of PSVT in pregnant women by trimester. METHODS: From 2001 to 2012, all pregnant women in Taiwan were monitored for PSVT events. Women who visited the emergency department or were admitted for symptomatic PSVT were enrolled in this study, and those with congenital heart diseases were excluded. RESULTS: A total of 2,387,588 pregnancies (1,623,596 mothers) were analyzed. For the women with no previous history of a PSVT event, the incidence rates of symptomatic PSVT were 15, 33, and 60 per 100,000 pregnancies during the first, second, and third trimester, respectively. For the women with a previous history of PSVT, the incidence rates were 5625, 9525, and 11526 per 100,000 pregnancies, respectively. Most PSVT events occurred during the third trimester. CONCLUSIONS: In this Taiwanese cohort of pregnant women there was a stepwise increase in the incidence of symptomatic PSVT, which peaked during the third trimester. A past history of PSVT was associated with a higher risk of recurrence during pregnancy. We suggest that clinicians should be aware of this trend. Prompt management of PSVT events may prevent maternal and fetal complications.

One-Year Mortality Risk Stratification in Patients Hospitalized for Acute Decompensated Heart Failure: Construction of TSOC-HFrEF Risk Scoring Model.

BACKGROUND: Most previous risk prediction models in patients hospitalized for heart failure (HF) are derived from populations in Western countries, and it is unclear whether these models are applicable to Asian populations. This study aimed to construct a risk score system for predicting one-year mortality risk in Asian patients and to compare the applicability of this risk score system with the 3C-HF score system. METHODS: We used the population in the Taiwan Society of Cardiology-Heart Failure with Reduced Ejection Fraction (TSOC-HFrEF) registry, which is a prospective cohort of patients admitted for acute decompensated heart failure (ADHF) in Taiwan. The risk score system was constructed using multivariate Cox-model derived coefficients. A bootstrapping procedure was also used for bias-corrected evaluations. Comparisons between this constructed model and the 3C-HF score prediction model were evaluated using calibration plots and area under curve (AUC)/receiver operating characteristic (ROC) curve. RESULTS: Patients with complete data (n = 1127) in the TSOC-HFrEF registry were analyzed. During one year of follow-up, 14.5% (n = 163) of the patients died. A risk score system was constructed with the following predictors: body mass index, diastolic blood pressure, dyslipidemia, diabetes, aortic regurgitation, QRS duration, hemoglobin concentration, and digoxin usage. Compared to the 3C-HF score system, this risk score system had a similar discriminatory ability (AUC/ROC values of 0.675 and 0.636, p = 0.127) and both were well-calibrated in the Taiwan population. CONCLUSIONS: The proposed risk score system for predicting one-year all-cause mortality in Taiwanese patients with ADHF may facilitate risk stratification in Asian patients with HF.

Serum asprosin levels and bariatric surgery outcomes in obese adults.

BACKGROUND/OBJECTIVES: Asprosin is a novel fasting-induced glucogenic and orexigenic protein hormone. The clinical function of asprosin in obesity is currently unknown. This study investigated the association between asprosin abundance and the outcome of bariatric surgery. SUBJECTS/METHODS: Patients with body mass index more than 35 kg/m2 were recruited for the Obesity and Clock for Elegant Aging Registry in 2011-2016. Body weight changes, blood sugar, and asprosin were assessed in 117 patients receiving bariatric surgery and 57 non-obese subjects as normal control. Primary outcomes of excess weight loss percentage at 6 months after bariatric surgery were determined at follow-up. RESULTS: Asprosin levels were significantly higher in obese patients than in non-obese subjects (2360 ± 5094 vs. 307 ± 832 ng/ml, p < 0.0001). Multivariate analyses showed a significant association of asprosin abundance with excess body weight loss percentage at 6 months after surgery (p < 0.0001). After adjusted for age, sex, smoking, HbA1c, cholesterol, and triglyceride, serum asprosin level was the only independent predictor of 6 months excess weight loss percentage after bariatric surgery. Asprosin levels decreased significantly 6 months after bariatric surgery (162.2 ± 169.1 ng/ml). Furthermore, there was no association between asprosin and serum glucose levels in our study. CONCLUSION: This study provides novel evidence that higher asprosin concentrations before bariatric surgery were associated with the weight reduction magnitude at 6 months after surgery. Further studies are warranted to investigate whether asprosin has direct functions to modulate body weight regulation in humans after bariatric surgery.

Effectiveness and safety of non-vitamin-K antagonist oral anticoagulants versus warfarin in atrial fibrillation patients with thrombocytopenia.

Patients with thrombocytopenia were excluded from major clinical trials that investigated non-vitamin-K antagonist oral anticoagulants (NOACs) for stroke prevention in atrial fibrillation (AF). The aim of this study was to evaluate the effectiveness and safety of NOAC versus warfarin in AF patients with thrombocytopenia. From 2010 to 2017, a cohort study based on electronic medical records of a multi-center healthcare provider in Taiwan and included 8239 anticoagulated AF patients (age 77.0 ± 7.3 years, 48.0% female). Patients were divided into two subgroups: 7872 patients with a normal platelet count and 367 patients (4.4%) with thrombocytopenia, which was defined as a platelet count less than 100 × 103/µL. We performed Cox proportional hazard analyses to compare the risks of ischemic stroke or systemic embolism (IS/SE), major bleeding, and death between NOAC and warfarin therapies in patients with a normal platelet count and those with thrombocytopenia, respectively. In patients with a normal platelet count, NOAC therapy (n = 4904) was associated with a significantly lower risk of major bleeding, with no difference in the risk of IS/SE or death when compared with warfarin therapy (n = 2968). In patients with thrombocytopenia, NOAC therapy (n = 181) was associated with a lower tendency for major bleeding (aHR 0.45, 95% CI 0.16-1.14) with no significant difference in IS/SE (aHR 0.94, 95% CI 0.29-2.91) or death (aHR 0.95, 95% CI 0.46-1.95) when compared with warfarin therapy (n = 186). NOAC therapy is a reasonable choice for stroke prevention in AF patients with thrombocytopenia.

Targeted Next Generation Sequencing for Genetic Mutations of Dilated Cardiomyopathy.

BACKGROUND: Approximately one-third of cases of dilated cardiomyopathy (DCM) are caused by genetic mutations. With new sequencing technologies, numerous variants have been associated with this inherited cardiomyopathy, however the prevalence and genotype-phenotype correlations in different ethnic cohorts remain unclear. This study aimed to investigate the variants in Chinese DCM patients and correlate them with clinical presentations and prognosis. METHODS AND RESULTS: From September 2013 to December 2016, 70 index patients underwent DNA sequencing for 12 common disease-causing genes with next generation sequencing. Using a bioinformatics filtering process, 12 rare truncating variants (7 nonsense variants, 4 frameshift variants, and 1 splice site variant) and 29 rare missense variants were identified. Of these, 3 patients were double heterozygotes and 10 patients were compound heterozygotes. Overall, 47.1% (33/70) of the index patients had the seputatively pathogenic variants. The majority (33/41, 80.4%) of these variants were located in titin (TTN). More than 80% of the TTN variants (27/33, 81.8%) were distributed in the A band region of the sarcomere. Patients carrying these variants did not have a different phenotype in disease severity, clinical outcome and reversibility of ventricular function compared with non-carriers. CONCLUSIONS: Several new rare variants were identified in a Chinese population in this study, indicating that there are ethnic differences in genetic mutations in DCM patients. TTN remains the major disease-causing gene. Our results could be a reference for future genetic tests in Chinese populations. No specific genotype-phenotype correlations were found, however a prospective large cohort study may be needed to confirm our findings.