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BACKGROUND: Patients with myocardial infarction (MI) can have disturbed sleep, but little is known about the efficacy of light therapy on sleep and prognosis of patients with MI. We conducted a randomized controlled study to investigate its efficacy. MATERIAL AND METHODS: This preliminary study included 34 patients with MI. They were randomized into the blue light and the white light groups during their stay in intensive care unit. 17 age and gender matched healthy controls were also enrolled. Actigraphy was used to evaluate objective sleep since enrollment. Delirium scales were used to screen delirium. Lab work-up including vitamin D level was performed at the baseline and discharge. We used Mann-Whitney U test or Wilcoxon signed-rank test to compare the difference between the MI group and the healthy control group, and the group difference after receiving light therapy. RESULTS: Patients with MI had significantly lower vitamin D level than healthy controls (p<0.001). They also had significantly poorer sleep, as indicated by actigraphy parameters including sleep onset latency (p=0.01), sleep efficiency (p=0.002), wake after sleep onset (p<0.001) and awake times (p=0.002). No significant group difference was found by actigraphy after light therapy except a non-significant higher relative amplitude of the blue light group (p=0.061). Besides, vitamin D level of the blue light group increased significantly (p1=0.047, p2=0.045). CONCLUSIONS: Patients with MI had poorer sleep, highlighting the needs to develop interventions. Significantly increased vitamin D level and a non-significant better rest-active rhythm after light therapy suggest its potential with sleep and prognosis which warrants further investigation.
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OBJECTIVE: This study evaluates the feasibility and efficacy of implanting a leadless pacemaker at the right atrial appendage (RAA) in a preclinical minipig model, aiming to address the limitations of atrial pacing with current leadless devices like the Medtronic Micra, which is typically used for right ventricular implantation. METHODS: Four minipigs, each with a median body weight of 45.8 ± 10.0 kg, underwent placement of the Micra transcatheter pacing system (TPS) via the right femoral vein into the RAA apex. The pacing performance was assessed over 1-week (short-term) and 3-month (long-term) periods. OUTCOMES: The initial findings indicated successful implantation, with satisfactory intrinsic R-wave amplitudes and pacing threshold. In the following period, the sensitivity, threshold, and impedance were stable with time. Notably, upon explanation at 3 months, a deep myocardial penetration by the device was observed, necessitating a redesign for safe long-term use in a growing subject's heart. CONCLUSION: While initial results suggest that RAA apex placement of the Micra TPS is promising for potential inclusion in a dual-chamber pacing system, the issue of myocardial penetration highlights the need for device redesign to ensure safety and effectiveness in long-term applications.
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Apéndice Atrial , Diseño de Equipo , Marcapaso Artificial , Porcinos Enanos , Animales , Porcinos , Apéndice Atrial/cirugía , Estudios de Factibilidad , Estimulación Cardíaca Artificial/métodosRESUMEN
Background: Previous studies have shown that global constructive work (CW) and wasted work (WW) predict response to cardiac resynchronization therapy (CRT). This study evaluated the predictive value of regional CW and WW for reverse remodeling and clinical outcomes after CRT. Methods: We performed a prospective study involving 134 CRT candidates with left bundle branch block and left ventricular ejection fraction ≤35%. Global and regional CW and WW were calculated using pressure-strain loop analysis. CRT response was defined by reverse remodeling as a reduction of ≥15% in left ventricular end-systolic volume after six months. Results: At six-month follow-up, 92 (69%) patients responded to CRT. Of the regional CW and WW measures, lateral wall (LW) CW and septal WW were most strongly and significantly correlated with reverse remodeling. At multivariate analysis, LW CW and septal WW were both independent determinants of reverse remodeling. When LW CW and septal WW were included in the model, global CW and WW were not independently associated with reverse remodeling. LW CW and septal WW predicted reverse remodeling with an area under the curve (AUC) of 0.783 (95% CI: 0.700-0.866) and 0.737 (95% CI: 0.644-0.831), respectively. Using both variables increased the AUC to 0.832 (95% CI: 0.755-0.908). Both LW CW ≤878â mmHg% (HR 2.01; 95% CI: 1.07-3.79) and septal WW ≤181â mmHg% (HR 2.60; 95% CI: 1.38-4.90) were significant predictors of combined death and HF hospitalization at two-year follow-up. Conclusion: LW CW and septal WW before CRT are important determinants of reverse remodeling and clinical outcomes.
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In dysfunctional arteriovenous fistulae (AVF) for hemodialysis access, neointimal hyperplasia (NH) is prone to occur in the region exposed to disturbed flow. We hypothesized that disturbed flow contributes to NH in AVF by inducing endothelial mesenchymal transition (EndMT) through activation of the osteopontin/CD44 axis. In rats with aortocaval fistula, a rodent model of AVF, we demonstrated development of EndMT and expression of osteopontin and CD44 specifically in the vicinity of the arteriovenous junction using immunostaining. Duplex scan confirmed this region was exposed to a disturbed flow. A mixed ultrastructural phenotype of endothelium and smooth muscle cells was found in luminal endothelial cells of the arteriovenous junction by electron microscopy ascertaining the presence of EndMT. Endothelial lineage tracing using Cdh5-Cre/ERT2;ROSA26-tdTomato transgenic mice showed that EndMT was involved in NH of AVF since the early stage and that the endothelial-derived cells contributed to 24% of neointimal cells. In human umbilical vein endothelial cells (HUVECs) in culture, osteopontin treatment induced EndMT, which was suppressed by CD44 knockdown. Exposure to low oscillatory wall shear stress using a parallel-plate system induced EndMT in HUVECs, also suppressed by osteopontin or CD44 knockdown. In AVF of CD44 knockout mice, EndMT was mitigated and NH decreased by 35% compared to that in wild-type mice. In dysfunctional AVF of patients with uremia, expressions of osteopontin, CD44, and mesenchymal markers in endothelial cells overlying the neointima was also found by immunostaining. Thus, the osteopontin/CD44 axis regulates disturbed flow-induced EndMT, plays an important role in neointimal hyperplasia of AVF, and may act as a potential therapeutic target to prevent AVF dysfunction.
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Neointima , Osteopontina , Animales , Humanos , Ratones , Ratas , Endotelio/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/patología , Receptores de Hialuranos/genética , Receptores de Hialuranos/metabolismo , Hiperplasia/patología , Neointima/patología , Osteopontina/genética , Diálisis Renal/efectos adversosRESUMEN
Background: In patients with heart failure (HF), circulating neutrophil gelatinase-associated lipocalin (NGAL) level is increased, which is considered to be a predictor of mortality or renal outcomes. The expression of NGAL in the heart and kidney and its role in HF remain unclear. Methods: Aortocaval fistula was created in rats as a model of volume overload (VO)-induced HF. Results: During the development of HF, NGAL expression was upregulated in the heart but not in the kidney at both transcriptional and translational levels in the compensatory and HF phases, with a similar level in both phases. Cardiomyocytes were identified as the cell type responsible for NGAL expression. Consistent with the myocardial NGAL expression pattern, the plasma NGAL level was increased in both phases, and the level was not significantly different between both phases. We demonstrated the presence of a matrix metalloproteinase (MMP)-9/NGAL complex in cultured medium of cardiomyocytes isolated from volume-overloaded hearts by gelatin zymography. Formation of MMP-9/NGAL complex was shown to enhance the enzymatic activity of MMP-9. We found that early growth response (Egr)-1 was upregulated in the heart in both compensatory and HF phases. In neonatal cardiomyocytes, Egr-1 overexpression induced the gene expression of NGAL, which was dose-dependently suppressed by an interleukin-1 receptor antagonist. Conclusions: During the development of HF due to VO, NGAL was upregulated in the heart but not in the kidney in both compensatory and HF phases, with a similar expression level. Myocardial NGAL upregulation enhanced MMP-9 activity through formation of the MMP-9/NGAL complex. The expression of myocardial NGAL was regulated by Egr-1.
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Purpose: We formulated and tested ensemble learning models to classify axial length (AXL) from choroidal thickness (CT) as indicated on fovea-centered, 2D single optical coherence tomography (OCT) images. Design: Retrospective cross-sectional study. Participants: We analyzed 710 OCT images from 355 eyes of 188 patients. Each eye had 2 OCT images. Methods: The CT was estimated from 3 points of each image. We used five machine-learning base algorithms to construct the classifiers. This study trained and validated the models to classify the AXLs eyes based on binary (AXL < or > 26 mm) and multiclass (AXL < 22 mm, between 22 and 26 mm, and > 26 mm) classifications. Results: No features were redundant or duplicated after an analysis using Pearson's correlation coefficient, LASSO-Pattern search algorithm, and variance inflation factors. Among the positions, CT at the nasal side had the highest correlation with AXL followed by the central area. In binary classification, our classifiers obtained high accuracy, as indicated by accuracy, recall, positive predictive value (PPV), negative predictive value (NPV), F1 score, and area under ROC curve (AUC) values of 94.37, 100, 90.91, 100, 86.67, and 95.61%, respectively. In multiclass classification, our classifiers were also highly accurate, as indicated by accuracy, weighted recall, weighted PPV, weighted NPV, weighted F1 score, and macro AUC of 88.73, 88.73, 91.21, 85.83, 87.42, and 93.42%, respectively. Conclusions: Our binary and multiclass classifiers classify AXL well from CT, as indicated on OCT images. We demonstrated the effectiveness of the proposed classifiers and provided an assistance tool for physicians.
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Derangements in cardiac energy metabolism have been shown to contribute to the development of heart failure (HF). This study combined transcriptomics and metabolomics analyses to characterize the changes and reversibility of cardiac energetics in a rat model of cardiac volume overload (VO) with the creation and subsequent closure of aortocaval fistula. Male Sprague-Dawley rats subjected to an aortocaval fistula surgery for 8 and 16 weeks exhibited characteristics of compensated hypertrophy (CH) and HF, respectively, in echocardiographic and hemodynamic studies. Glycolysis was downregulated and directed to the hexosamine biosynthetic pathway (HBP) and O-linked-N-acetylglucosaminylation in the CH phase and was further suppressed during progression to HF. Derangements in fatty acid oxidation were not prominent until the development of HF, as indicated by the accumulation of acylcarnitines. The gene expression and intermediates of the tricarboxylic acid cycle were not significantly altered in this model. Correction of VO largely reversed the differential expression of genes involved in glycolysis, HBP, and fatty acid oxidation in CH but not in HF. Delayed correction of VO in HF resulted in incomplete recovery of defective glycolysis and fatty acid oxidation. These findings may provide insight into the development of innovative strategies to prevent or reverse metabolic derangements in VO-induced HF.
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Insuficiencia Cardíaca , Transcriptoma , Animales , Metabolismo Energético/genética , Ácidos Grasos/metabolismo , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/metabolismo , Masculino , Metabolómica , Miocardio/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Arrhythmias are not always easy to capture because they are often paroxysmal or asymptomatic. METHODS: Using the CHA2DS2-VASc score for arrhythmia risk assessment, a 14-day electrocardiography monitor patch was used to evaluate patients with no documented history of arrhythmia. RESULTS: Ninety-three patients (mean age 59.8 ± 12.0 years, 46.2% female) received 14-day electrocardiography telemonitoring, and 14 patients (15%) were diagnosed with arrhythmias during a follow-up of 1004.4 person-days (mean recorded days 10.8 ± 4.1). The patients who were detected to have arrhythmias were older and had a higher prevalence of heart failure and chronic kidney disease. The result showed that arrhythmias were more likely to develop during a 14-day monitoring period in the patients with a CHA2DS2-VASc score of ≥ 3 or ≥ 4. Atrioventricular block was more likely to be detected in the patients with a CHA2DS2-VASc score of ≥ 3 or ≥ 4 during 7-day or 14-day monitoring periods. Ventricular tachycardia was also more likely to be detected in the patients with a CHA2DS2-VASc score of ≥ 4 or ≥ 5 during a 14-day monitoring period. When evaluating the risk of arrhythmia, a CHA2DS2-VASc score of ≥ 3 or ≥ 4 was associated with a higher risk of any arrhythmias during a 14-day monitoring period, while a CHA2DS2-VASc score of ≥ 4 was associated with a higher risk of any arrhythmias during a 7-day monitoring period. CONCLUSIONS: The results may suggest that a 14-day monitoring period is more favorable to detect arrhythmias. Atrioventricular block and ventricular tachycardia were more likely to develop in the patients with a higher CHA2DS2-VASc score.
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Background and Purpose: Data on clinical outcomes for nonvitamin K antagonist oral anticoagulant (NOACs) and warfarin in patients with atrial fibrillation and cancer are limited, and patients with active cancer were excluded from randomized trials. We investigated the effectiveness and safety for NOACs versus warfarin among patients with atrial fibrillation with cancer. Methods: In this nationwide retrospective cohort study from Taiwan National Health Insurance Research Database, we identified a total of 6274 and 1681 consecutive patients with atrial fibrillation with cancer taking NOACs and warfarin from June 1, 2012, to December 31, 2017, respectively. Propensity score stabilized weighting was used to balance covariates across study groups. Results: There were 1031, 1758, 411, and 3074 patients treated with apixaban, dabigatran, edoxaban, and rivaroxaban, respectively. After propensity score stabilized weighting, NOAC was associated with a lower risk of major adverse cardiovascular events (hazard ratio, 0.63 [95% CI, 0.500.80]; P=0.0001), major adverse limb events (hazard ratio, 0.41 [95% CI, 0.240.70]; P=0.0010), venous thrombosis (hazard ratio, 0.37 [95% CI, 0.230.61]; P<0.0001), and major bleeding (hazard ratio, 0.73 [95% CI, 0.560.94]; P=0.0171) compared with warfarin. The outcomes were consistent with either direct thrombin inhibitor (dabigatran) or factor Xa inhibitor (apixaban, edoxaban, and rivaroxaban) use, among patients with stroke history, and among patients with different type of cancer and local, regional, or metastatic stage of cancer (P interaction >0.05). When compared with warfarin, NOAC was associated with lower risk of major adverse cardiovascular event, and venous thrombosis in patients aged <75 but not in those aged ≥75 years (P interaction <0.05). Conclusions: Thromboprophylaxis with NOACs rather than warfarin should be considered for the majority of the atrial fibrillation population with cancer.
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Anticoagulantes/uso terapéutico , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Neoplasias/complicaciones , Administración Oral , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/prevención & control , Estudios de Cohortes , Femenino , Hemorragia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Estudios Retrospectivos , Accidente Cerebrovascular/prevención & control , Taiwán , Resultado del Tratamiento , Trombosis de la Vena/prevención & control , Vitamina K/antagonistas & inhibidores , Warfarina/uso terapéuticoRESUMEN
BACKGROUND: To evaluate the performance of a singlelead, 14-day continuous electrocardiogram (ECG) patch for the detection of arrhythmias compared to conventional 24-h monitoring. METHODS: This prospective clinical trial enrolled patients suspected of arrhythmias but not diagnosed by 12lead ECGs. Each patient underwent a 24-h Holter and 14-day ECG patch simultaneously. Seven types of arrhythmias were classified: supraventricular tachycardia (SVT, repetitive atrial beats >4 beats), irregular SVT without P wave (>4 beats), AF/AFL (irregular SVT without P wave ≥30 s), pause ≥3 s, atrioventricular block (AVB; Mobitz type II, third-degree, two to one or high degree AVB), ventricular tachycardia (VT), and polymorphic VT. RESULTS: A total of 158 patients were recruited (mean wear time:12.3 ± 3.2 days). The overall arrhythmia detection rate was higher with 14-day ECG patches (59.5%) compared to 24-h Holter (19.0%, P < 0.001). Up to 87.2% of arrhythmias recorded with 14-day ECG patches were not associated with symptoms. The 14-day ECG patch was associated with higher detection rates compared to the 24-h Holter in patients with SVT (52.5% versus 15.8%, P < 0.001), irregular SVT without P wave (12.7% versus 4.4%, P = 0.002), AF/AFL (9.5% versus 3.8%, P = 0.042), and critical arrhythmias (pause ≥3 s, AVB, VT, polymorphic VT) (16.5% versus 2.5%, P < 0.001). The 14-day ECG patch detected more than 2 types of arrhythmias in 5.1% of patients. No serious adverse events in patients wearing the 14-day ECG patch were reported. CONCLUSIONS: The 14-day ECG patch outperformed 24-h Holter to detect overall, asymptomatic, critical and multiple arrhythmias. It is safe and has the potential to identify individuals with hidden arrhythmias, especially those with critical arrhythmias.
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Electrocardiografía Ambulatoria , Taquicardia Supraventricular , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/epidemiología , Electrocardiografía , Humanos , Estudios Prospectivos , Taquicardia Supraventricular/diagnóstico , Taquicardia Supraventricular/epidemiologíaRESUMEN
AIMS: To investigate the effectiveness, safety, and outcomes of lower limb events for non-vitamin K antagonist oral anticoagulants (NOACs) vs. warfarin among atrial fibrillation (AF) patients with concomitant peripheral artery disease (PAD). METHODS AND RESULTS: In this nationwide retrospective cohort study collected from Taiwan National Health Insurance Research Database, a total of 5768 and 2034 consecutive AF patients with PAD patients taking NOACs or warfarin were identified from 1 June 2012 to 31 December 2017, respectively. We used propensity score stabilized weighting to balance covariates across study groups. In the cohort, there were 89% patients were taking low-dose NOAC (dabigatran 110 mg twice daily, rivaroxaban 10-15 mg daily, apixaban 2.5 mg twice daily, or edoxaban 30 mg daily). Non-vitamin K antagonist oral anticoagulant was associated with a comparable risk of ischaemic stroke, and a lower risk of acute myocardial infarction [hazard ratio (HR): 0.61, 95% confidence interval (CI): 0.42-0.87; P = 0.007], lower extremity thromboembolism (HR: 0.56, 95% CI: 0.44-0.72; P < 0.0001), revascularization procedure (HR: 0.58, 95% CI: 0.47-0.72; P < 0.0001), lower limb amputation (HR: 0.32, 95% CI: 0.23-0.46; P < 0.0001), and all major bleeding (HR: 0.64, 95% CI: 0.50-0.80; P = 0.0001) than warfarin after weighting. The advantage of NOACs over warfarin persisted in high-risk subgroups including patients of ≥75 years of age, diabetes, renal impairment, or use of concomitant antiplatelet agent. CONCLUSION: This population-based study indicated that NOACs were associated with a comparable risk of ischaemic stroke, and a significantly lower risk of major adverse limb events and major bleeding than warfarin among AF patients with concomitant PAD. Therefore, thromboprophylaxis with NOACs may be considered for such patients.
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Anticoagulantes , Fibrilación Atrial , Enfermedad Arterial Periférica , Warfarina , Administración Oral , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Fibrilación Atrial/tratamiento farmacológico , Humanos , Enfermedad Arterial Periférica/complicaciones , Enfermedad Arterial Periférica/tratamiento farmacológico , Warfarina/efectos adversosRESUMEN
BACKGROUND: Evidence of clinical outcomes for oral anticoagulants and antiplatelet treatment (APT) in patients with atrial fibrillation (AF) and critical limb ischemia (CLI) is very limited. METHODS: In this nationwide retrospective cohort study collected from Taiwan National Health Insurance Research Database, 1223 patients with AF and CLI taking direct-acting oral coagulants (DOACs), warfarin, or APT were identified from June 1, 2012, to December 31, 2017. We used propensity score stabilized weighting (PSSW) to balance covariates across study groups. RESULTS: After PSSW, DOAC (n = 446) was associated with lower risks of ischemic stroke/systemic embolism (IS/SE), all major adverse limb events, and all major bleeding events compared with warfarin (n = 237). DOAC was associated with lower risks of IS/SE, acute myocardial infarction (AMI), and all major adverse limb events and a comparable risk of major bleeding events compared with APT (n = 540). DOAC has a lower risk of composite net-clinical-benefit outcome (IS/SE, AMI, all major adverse limb events, plus all major bleeding events) compared with warfarin (hazard ratio [HR]: 0.48; 95% confidence interval [CI]: 0.35-0.65; P < 0.0001) or APT (HR: 0.44; 95% CI: 0.34-0.56; P < 0.0001). The composite net-clinical-benefit outcome was comparable for warfarin vs APT. The reduced risk of net-clinical-benefit outcome for DOAC vs warfarin or APT persisted in high subgroups including age > 75 years, presence of diabetes mellitus, or chronic kidney disease. CONCLUSIONS: DOAC was associated with a significantly lower risk of composite net-clinical-benefit outcome than either warfarin or APT in patients with AF and concomitant CLI. Further prospective study is necessary to validate the findings in the future.
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Fibrilación Atrial/tratamiento farmacológico , Inhibidores del Factor Xa/uso terapéutico , Isquemia/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Anticoagulantes/uso terapéutico , Fibrilación Atrial/epidemiología , Estudios de Cohortes , Embolia/epidemiología , Extremidades/irrigación sanguínea , Hemorragia/epidemiología , Humanos , Isquemia/epidemiología , Accidente Cerebrovascular Isquémico/epidemiología , Estudios Retrospectivos , Taiwán/epidemiología , Warfarina/uso terapéuticoRESUMEN
PURPOSE: Whether direct oral anticoagulants (DOACs) are more effective and safer than warfarin among Asian patients with non-valvular atrial fibrillation (NVAF) undergoing dialysis remains unclear. METHODS: We first compared the risks of ischemic stroke/systemic embolism (IS/SE) and major bleeding associated with DOACs compared with warfarin, in NVAF Asians undergoing dialysis using the Taiwan National Health Insurance Research Database (NHIRD) (Aim 1). Next, we searched PubMed and Medline from January 1, 2010 until January 31, 2020, to perform a systematic review and meta-analysis of all observational real-world studies comparing DOACs with warfarin specifically focused on NVAF patients with stage 4 or 5 chronic kidney disease undergoing dialysis (Aim 2). Finally, we tested the hypothesis whether AF patients undergoing dialysis treated with OACs (warfarin and DOACs) would be associated with lower risk of adverse clinical outcomes as compared to those without OACs using the Taiwan NHIRD (Aim 3). RESULTS: From June 1, 2012, to December 31, 2017, a total of 3237 and 9263 NVAF patients comorbid with ESRD receiving oral anticoagulant (OACs) (490 on DOAC, 2747 on warfarin) or no OACs, respectively, were enrolled. Propensity score matching was used to balance covariates across the study groups. For the comparison of DOAC vs. warfarin (Aim 1), DOACs had comparable risks of IS/SE and major bleeding to warfarin in our present cohort. From the original 85 results retrieved, nine studies (including our study) with a total of 6490 and 22,494 patients treated with DOACs and warfarin were included in the meta-analysis, respectively. There were 5343 (82%) and 20,337 (90%) patients treated with DOACs and warfarin undergoing dialysis, respectively. The pooled meta-analysis also indicated no difference of the effectiveness (HR:0.90; [95%CI:0.74-1.10]; P = 0.32) and safety outcomes (HR:0.75; [95%CI:0.54-1.05]; P = 0.09) between DOACs and warfarin (Aim 2). For the comparison of OAC (+) vs. OAC (-) (Aim 3), OAC-treatment was associated with a higher risk of IS/SE (hazard ratio (HR):1.54; [95% confidential interval (CI):1.29-1.84];P < 0.0001) and comparable risk of major bleeding compared to those without OAC treatment. CONCLUSIONS: DOACs did not provide benefit over warfarin regarding effectiveness and safety in AF patients undergoing dialysis. The use of OAC was not associated with a lower risk of IS/SE in ESRD AF patients when compared to those without OAC use.
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Anticoagulantes/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Inhibidores del Factor Xa/uso terapéutico , Diálisis Renal/estadística & datos numéricos , Insuficiencia Renal Crónica/terapia , Warfarina/uso terapéutico , Administración Oral , Anciano , Anciano de 80 o más Años , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Embolia/prevención & control , Inhibidores del Factor Xa/administración & dosificación , Inhibidores del Factor Xa/efectos adversos , Femenino , Hemorragia/inducido químicamente , Humanos , Revisión de Utilización de Seguros , Masculino , Gravedad del Paciente , Accidente Cerebrovascular/prevención & control , Taiwán/epidemiología , Warfarina/administración & dosificación , Warfarina/efectos adversosRESUMEN
BACKGROUND: Whether sodium glucose co-transporter 2 inhibitors (SGLT2i) are associated with a lower risk of cardiovascular as well as adverse lower limb events in patients with type-2 diabetes mellitus (T2DM) and concomitant peripheral artery disease (PAD) is unclear. We aimed to evaluate the risk of cardiovascular and limb events, and death associated with the use of SGLT2i compared with dipeptidyl peptidase-4 inhibitors (DPP4i) among a longitudinal and national cohort of patients with T2DM. METHODS: In this nationwide retrospective cohort study based on the Taiwan National Health Insurance Research Database, we identified a total of 11,431 and 93,972 consecutive T2DM patients with PAD taking SGLT2i and DPP4i, respectively, from May 1, 2016, to December 31, 2017. We used 1:1 propensity score matching (PSM) to balance covariates across study groups. Patients were followed from the drug index date until the occurrence of clinical outcomes, death, discontinuation of the index drug, or the end of the study period, whichever occurred first. RESULTS: Overall, 56% and 44% of the patients were treated with dapagliflozin and empagliflozin, respectively. The use of SGLT2i had comparable risks of ischemic stroke and acute myocardial infarction, and was associated with lower risks of congestive heart failure (CHF) [hazard ratio (HR): 0.66; 95% confidence interval (CI) 0.49-0.89; p = 0.0062], lower limb ischemia requiring revascularization (HR: 0.73; 95% CI 0.54-0.98; p = 0.0367) or amputation (HR: 0.43; 95% CI 0.30-0.62; p < 0.0001), and cardiovascular death (HR: 0.67; 95% CI 0.49-0.90; p = 0.0089) when compared with the DDP4i group after PSM. The subgroup analysis revealed consistent results for CHF and major adverse limb outcomes for SGLT2i versus DPP4i among patients aged ≥ 75 years, the presence of chronic kidney disease and established cardiovascular disease was consistent with the main analysis. CONCLUSIONS: SGLT2i were associated with lower risks of CHF and adverse lower limb events compared with DPP4i among patients with T2DM and PAD in real-world practice.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Enfermedad Arterial Periférica/terapia , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Anciano , Anciano de 80 o más Años , Amputación Quirúrgica , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidad , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Femenino , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/prevención & control , Humanos , Incidencia , Recuperación del Miembro , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/mortalidad , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Taiwán/epidemiología , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Evidence of adverse clinical outcomes for non-vitamin K antagonist oral anticoagulant (NOACs) and warfarin in patients with atrial fibrillation (AF) and diabetes mellitus are limited. We investigated the effectiveness, safety, and major adverse limb events for NOACs versus warfarin among diabetic AF patients. METHODS: In this nationwide retrospective cohort study collected from Taiwan National Health Insurance Research Database, we identified a total of 20,967 and 5812 consecutive AF patients with diabetes taking NOACs and warfarin from June 1, 2012, to December 31, 2017, respectively. We used propensity-score stabilized weighting to balance covariates across study groups. RESULTS: NOAC was associated with a lower risk of major adverse cardiovascular events (MACE) (adjusted hazard ratio (aHR):0.88; [95% confidential interval (CI) 0.78-0.99]; P = 0.0283), major adverse limb events (MALE) (aHR:0.72;[95% CI 0.57-0.92]; P = 0.0083), and major bleeding (aHR:0.67;[95% CI 0.59-0.76]; P < 0.0001) compared to warfarin. NOACs decreased MACE in patients of ≥ 75 but not in those aged < 75 years (P interaction = 0.01), and in patients with ischemic heart disease (IHD) compared to those without IHD (P interaction < 0.01). For major adverse limb events, the advantage of risk reduction for NOAC over warfarin persisted in high risk subgroups including age ≥ 75 years, chronic kidney disease, IHD, peripheral artery disease, or use of concomitant antiplatelet drugs. CONCLUSION: Among diabetic AF patients, NOACs were associated with a lower risk of thromboembolism, major bleeding, and major adverse limb events than warfarin. Thromboprophylaxis with NOACs should be considered in the diabetic AF population with a high atherosclerotic burden.
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Amputación Quirúrgica , Anticoagulantes/administración & dosificación , Fibrilación Atrial/tratamiento farmacológico , Diabetes Mellitus/epidemiología , Inhibidores del Factor Xa/administración & dosificación , Extremidad Inferior/irrigación sanguínea , Enfermedad Arterial Periférica/terapia , Procedimientos Quirúrgicos Vasculares , Warfarina/administración & dosificación , Administración Oral , Anciano , Anciano de 80 o más Años , Amputación Quirúrgica/efectos adversos , Anticoagulantes/efectos adversos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Bases de Datos Factuales , Diabetes Mellitus/diagnóstico , Inhibidores del Factor Xa/efectos adversos , Femenino , Hemorragia/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Seguridad del Paciente , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/epidemiología , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Taiwán/epidemiología , Factores de Tiempo , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares/efectos adversos , Warfarina/efectos adversosRESUMEN
OBJECTIVE: Patients with hyperthyroidism were excluded from the randomized clinical trials of direct oral anticoagulants (DOACs) for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). METHODS: We performed a nationwide retrospective cohort study using data from the Taiwan National Health Insurance Research Database. We enrolled 3213 and 1181 NVAF patients with hyperthyroidism who were taking DOACs and warfarin, respectively, from June 1, 2012 to December 31, 2017. We also enrolled 53 591 and 16 564 NVAF patients without hyperthyroidism, taking DOACs and warfarin, respectively. We used propensity score stabilized weights (PSSWs) to balance covariates across the study groups. We also used 1:4 matching on both taking DOACs, with (n = 3213) and without hyperthyroidism (n = 12 852); and both taking warfarin, with (n = 1181) and without hyperthyroidism (n = 4724). RESULTS: After PSSW, DOAC had a comparable risk of ischemic stroke/systemic embolism (IS/SE) and a lower risk of major bleeding (hazard ratio [HR] 0.65; 95% confidential interval [CI], 0.44-0.96; P = 0.0295) than warfarin among patients with hyperthyroidism. There were comparable risks of IS/SE and major bleeding between those patients with and without hyperthyroidism. However, among patients taking warfarin, those with hyperthyroidism had a lower risk of IS/SE than those without hyperthyroidism (HR 0.61; 95% CI, 0.43-0.86; P = 0.0050). CONCLUSION: Among NVAF Asian patients with concomitant hyperthyroidism, DOACs may be an effective and safer alternative to warfarin. Thromboprophylaxis with DOACs may be considered for such patients, and it is important to validate this finding in further prospective study.
Asunto(s)
Anticoagulantes/administración & dosificación , Fibrilación Atrial/tratamiento farmacológico , Hipertiroidismo/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/epidemiología , Estudios de Cohortes , Comorbilidad , Bases de Datos Factuales , Femenino , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Humanos , Hipertiroidismo/complicaciones , Hipertiroidismo/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/epidemiología , Taiwán/epidemiología , Resultado del Tratamiento , Warfarina/administración & dosificación , Warfarina/efectos adversosRESUMEN
BACKGROUND: Studies have reported conflicting findings on the infection risk posed by intravenous iron supplementation among hemodialysis (HD) patients. We used a novel study design to assess associations between intravenous iron and infectious diseases. METHODS: Patients initiating HD between 1998 and 2008 were extracted from Taiwan's National Health Insurance Research Database. Their first infectious disease in the period between 1.5 years after dialysis initiation and 2010 was identified and defined as the index date. Through the case-crossover design, the odds of exposure to intravenous iron within the 1-month period immediately preceding the index date (i.e., the case period) were compared with iron exposure in three different matched control periods for the same enrollee, thus possibly reducing some unmeasured confounders. RESULTS: A total of 1410 patients who met our enrollment criteria were extracted from incident HD patients. The odds of intravenous iron exposure during the case period versus total control periods exhibited no significant difference (odds ratio: 1.000, 95% confidence interval: 0.75-1.33). In subgroup analyses, this association remained nonsignificant across patients with diabetes mellitus, heart failure, chronic lung disease, venous catheter for HD, and higher iron load. CONCLUSIONS: We found that intravenous iron supplementation did not increase short-term infection risk among HD patients.
Asunto(s)
Infecciones Bacterianas/etiología , Hematínicos/efectos adversos , Hierro/efectos adversos , Fallo Renal Crónico/terapia , Diálisis Renal/efectos adversos , Administración Intravenosa , Adulto , Anciano , Infecciones Bacterianas/microbiología , Estudios de Cohortes , Estudios Cruzados , Bases de Datos Factuales/estadística & datos numéricos , Diabetes Mellitus/epidemiología , Métodos Epidemiológicos , Femenino , Compuestos Férricos/administración & dosificación , Compuestos Férricos/efectos adversos , Sacarato de Óxido Férrico/administración & dosificación , Sacarato de Óxido Férrico/efectos adversos , Insuficiencia Cardíaca/epidemiología , Hematínicos/administración & dosificación , Humanos , Hierro/administración & dosificación , Complejo Hierro-Dextran/administración & dosificación , Complejo Hierro-Dextran/efectos adversos , Fallo Renal Crónico/epidemiología , Enfermedades Pulmonares/epidemiología , Masculino , Persona de Mediana Edad , Multimorbilidad , Programas Nacionales de Salud/estadística & datos numéricos , Taiwán/epidemiología , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Whether four direct oral anticoagulants (DOACs) are superior to warfarin in Asian patients with nonvalvular atrial fibrillation (NVAF) remains unclear. METHODS: This nationwide retrospective cohort study was based on data from Taiwan's National Health Insurance Research Database from June 1, 2012, to December 31, 2017, covering patients with NVAF taking edoxaban (n = 4,577), apixaban (n = 9,952), rivaroxaban (n = 33,022), dabigatran (n = 22,371), and warfarin (n = 19,761). Propensity score weighting was used to balance covariates across study groups. Patients were followed up until occurrence of study outcomes or end date of study. RESULTS: Edoxaban, apixaban, and rivaroxaban were associated with a lower risk of ischemic stroke/systemic embolism than warfarin. All DOACs had a lower risk of major bleeding than warfarin. Apixaban was associated with a lower risk of major bleeding than rivaroxaban and dabigatran, whereas the risk of major bleeding was comparable between edoxaban and apixaban. The reduced risks of thromboembolism/major bleeding for the four DOACs persisted in high-risk subgroups, including those with chronic kidney disease, elderly patients (age ≥ 75 years), secondary stroke prevention, or CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, previous stroke/transient ischemic attack, vascular disease, age 65-74 years, and female sex) ≥ 4. A total of 2,924 (64%), 6,359 (64%), 31,108 (94%), and 19,821 (89%) patients received low-dose edoxaban (15-30 mg/d), apixaban (2.5 mg bid), rivaroxaban (10-15 mg/d), and dabigatran (110 mg bid), respectively. The effectiveness/safety outcomes with the four low-dose DOACs compared with warfarin were consistent with the main analysis. CONCLUSIONS: In the largest real-world practice study among Asian patients with NVAF, four DOACs were associated with a comparable or lower risk of thromboembolism, and a lower risk of bleeding than warfarin. There was consistency even among high-risk subgroups and whether standard-or low-dose regimens were compared.
Asunto(s)
Anticoagulantes/uso terapéutico , Pueblo Asiatico , Fibrilación Atrial/complicaciones , Hemorragia/epidemiología , Accidente Cerebrovascular/epidemiología , Tromboembolia/epidemiología , Administración Oral , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/tratamiento farmacológico , Dabigatrán/uso terapéutico , Bases de Datos Factuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pirazoles/uso terapéutico , Piridinas/uso terapéutico , Piridonas/uso terapéutico , Estudios Retrospectivos , Rivaroxabán/uso terapéutico , Taiwán , Tiazoles/uso terapéutico , Resultado del Tratamiento , Warfarina/uso terapéuticoRESUMEN
Background Liver cirrhotic patients with nonvalvular atrial fibrillation have been excluded from randomized clinical studies regarding oral anticoagulants for stroke prevention. Whether non-vitamin K antagonist oral anticoagulants ( NOAC s) are superior to warfarin for these patients remains unclear. Methods and Results This nationwide retrospective cohort study, with data collected from the Taiwan National Health Insurance Research Database, enrolled 2428 liver cirrhotic patients with nonvalvular atrial fibrillation taking apixaban (n=171), dabigatran (n=535), rivaroxaban (n=732), or warfarin (n=990) from June 1, 2012, to December 31, 2016. We used propensity score-based stabilized weights to balance covariates across study groups. Patients were followed until the occurrence of an event or the end date of study. The NOAC group (n=1438) showed risk of ischemic stroke/systemic embolism and intracranial hemorrhage comparable to that of the warfarin group (n=990) after adjustment. The NOAC group showed significantly lower risk of gastrointestinal bleeding (hazard ratio: 0.51 [95% CI, 0.32-0.79]; P=0.0030) and all major bleeding (hazard ratio: 0.51 [95% CI, 0.32-0.74]; P=0.0003) compared with warfarin group. Overall, 90% (n=1290) of patients were taking a low-dose NOAC (apixaban 2.5 mg twice daily, rivaroxaban 10-15 mg daily, or dabigatran 110 mg twice daily). The subgroup analysis indicated that both dabigatran and rivaroxaban showed lower risk of all major bleeding than warfarin. The advantage of lower gastrointestinal and all major bleeding with NOACs over warfarin is contributed by those subgroups with either nonalcoholic or nonadvanced liver cirrhosis. Conclusions NOACs have a risk of thromboembolism comparable to that of warfarin and a lower risk of major bleeding among liver cirrhotic Asian patients with nonvalvular atrial fibrillation. Consequently, thromboprophylaxis with low-dose NOAC s may be considered for such patients.
Asunto(s)
Anticoagulantes/administración & dosificación , Antitrombinas/administración & dosificación , Fibrilación Atrial/tratamiento farmacológico , Cirrosis Hepática/epidemiología , Accidente Cerebrovascular/prevención & control , Tromboembolia/prevención & control , Administración Oral , Anciano , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Antitrombinas/efectos adversos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Dabigatrán/administración & dosificación , Femenino , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Humanos , Cirrosis Hepática/diagnóstico , Masculino , Persona de Mediana Edad , Seguridad del Paciente , Pirazoles/administración & dosificación , Piridonas/administración & dosificación , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Rivaroxabán/administración & dosificación , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Taiwán/epidemiología , Tromboembolia/diagnóstico , Tromboembolia/epidemiología , Factores de Tiempo , Resultado del Tratamiento , Warfarina/administración & dosificaciónRESUMEN
BACKGROUND: Cirrhotic cardiomyopathy (CCM) refers to cardiac dysfunction in patients with liver cirrhosis, in the absence of other known cardiac disease. METHODS: Control group and patients diagnosed of liver cirrhosis without known cardiac disease or hepatocellular carcinoma were enrolled for this clinical observation study. Patients with diabetes mellitus, hypertension were excluded. Absolute global longitudinal strain, one-point carotid pulse wave velocity (one-point PWV) and various parameters were measured in resting status. RESULTS: There were 29 participants in the control group and 80 patients in the liver cirrhosis group. 27.8% of cirrhotic patients presented with normal systolic but abnormal diastolic functions and QTc prolongation that were compatible with CCM. 34.2% of cirrhotic patients presented with diastolic dysfunction in resting state comparing to 24.1% in control group. Systolic functions did not show conspicuous difference between cirrhosis and control group nor between compensated and decompensated cirrhosis, neither. Furthermore, one-point PWV was significantly higher in liver cirrhosis than in control group and higher in CCM than in non-CCM patients. One-point PWV predicted CCM and diastolic dysfunction in cirrhosis. Most importantly, its value > 1370cm/s predicted overall mortalities in decompensated cirrhosis (multivariable Cox analysis OR = 6.941) in addition to CTP score specifically in HCV related cirrhotic patients (AUC = 0.817). CONCLUSIONS: In patients with cirrhosis, 27.8% were diagnosed with CCM by resting cardiovascular parameters. One-point PWV increased in CCM, correlated with diastolic dysfunction. It also correlated with overall mortality in patients with hepatitis C virus (HCV) related decompensated cirrhosis. Further study may be needed to confirm its capability for assessing CV and mortality risks in HCV related decompensated cirrhotic patients.