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Abstract Aims The PIONEER‐HF and PARAGLIDE‐HF trials aimed to determine the efficacy and safety of the in‐hospital initiation of sacubitril/valsartan in patients hospitalized for AHF. However, whether the inclusion and exclusion criteria of the trials apply to patients encountered in real‐world routine care is unclear. This study aimed to investigate the applicability of the PIONEER‐HF and PARAGLIDE‐HF trials to real‐world AHF patients. Methods and results We identified 28 293 AHF hospitalized patients between August 2008 to August 2017 from the Chang Gung Research Database and classified them into four groups based on left ventricular ejection fraction (LVEF) and trial criteria. Cox proportional hazards models were used to compare the risk of HF hospitalization and cardiovascular (CV) death. We defined PIONEER‐HF eligible (n = 3683) and non‐eligible (n = 3502) patients with an LVEF ≤40%, and PARAGLIDE‐HF eligible (n = 5191) and non‐eligible (n = 5832) patients with an LVEF >40%. Over a mean follow‐up of 3.5 years, the PIONEER‐HF non‐eligible and eligible groups exhibited similar rates of HF hospitalization and CV death (41.1% vs. 41.8%, adjusted hazard ratio [aHR]: 0.95; 95% CI: 0.88–1.04). No significant difference was found in the composite outcome between PARAGLIDE‐HF non‐eligible and eligible groups (36.7% vs. 38.6%; aHR: 0.97; 95% CI: 0.90–1.04). Conclusions Using trial criteria, only 31.3% of AHF patients were eligible for sacubitril–valsartan. Yet, non‐eligible patients demonstrated similar outcomes to eligible patients, indicating a need for further evaluation of sacubitril–valsartan benefits in non‐eligible AHF patients.

Abstract Background Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a rare plasma cell (PC) neoplasm with associated paraneoplastic syndrome. According to the current diagnostic criteria, peripheral polyneuropathy and monoclonal PC proliferative disorder represent two mandatory criteria. Case presentation We report a 54-year-old male with peripheral neuropathy of bilateral lower limbs, sclerotic bone lesions, elevated vascular endothelial growth factor (VEGF) levels, splenomegaly, extravascular volume overload, endocrinopathy, and skin hemangiomas. Of note, serum and urine protein electrophoresis (PEP) and immunofixation electrophoresis (IFE) of this patient indicated undetectable M-protein and the normal ratio of free light chains κ and λ (FLC-R (κ/λ)). No monoclonal PCs were found in bone marrow examinations or biopsy of diseased bones. However, his clinical manifestations matched most of the diagnostic criteria. After excluding other diseases that are easily confused with POEMS syndrome, the diagnosis of variant POEMS syndrome with undetectable M-protein was proposed. The patient obtained clinically significant improvement and elevated VEGF returned to normal after 6 months of treatment with lenalidomide plus dexamethasone. Conclusions Monoclonal PC dyscrasia (M-protein) while being a mandatory criterion for POEMS syndrome is undetectable in a considerable amount of patients that otherwise demonstrate typical symptoms. Here, we reported a case of variant POEMS syndrome with featured clinical manifestations, elevated VEGF levels, and good response to therapies targeting PCs but no evidence of M-protein. Therefore, negative results in M-protein and monoclonal PCs aren’t enough to reject the diagnosis of POEMS syndrome. It is imperative to recognize the variant form of POEMS syndrome.

Background: The introduction of non-vitamin K antagonist oral anticoagulants (NOACs), with a non-inferior or superior clinical efficacy profile compared to vitamin K antagonists (VKAs), has significantly improved the safety profile and treatment adherence of patients with non-valvular atrial fibrillation (AF). However, few studies have compared the effectiveness and safety of NOACs. Therefore, we conducted this systematic review and network meta-analysis to compare the safety and clinical effectiveness of NOACs and VKAs in patients with non-valvular AF. Methods: An online bibliographic search was conducted to retrieve real-world evidence studies published between January 2019 and June 2022. Results: Dabigatran was associated with lower risks of major bleeding, ischemic stroke, and intracranial hemorrhage than warfarin. Among the NOACs, only dabigatran had a lower risk of all-cause mortality than warfarin. Dabigatran was also associated with lower risks of major bleeding and intracranial hemorrhage than rivaroxaban. Conclusion: Our meta-analysis confirms that dabigatran's real-world safety and clinical effectiveness align with the results of pivotal clinical trials.

Background The successful treatment and improvement of acute kidney injury (AKI) depend on early-stage diagnosis. However, no study has differentiated between the three stages of AKI and non-AKI patients following heart surgery. This study will fill this gap in the literature and help to improve kidney disease management in the future.Methods In this study, we applied Raman spectroscopy (RS) to uncover unique urine biomarkers distinguishing heart surgery patients with and without AKI. Given the amplified risk of renal complications post-cardiac surgery, this approach is of paramount importance. Further, we employed the partial least squares-support vector machine (PLS-SVM) model to distinguish between all three stages of AKI and non-AKI patients.Results We noted significant metabolic disparities among the groups. Each AKI stage presented a distinct metabolic profile: stage 1 had elevated uric acid and reduced creatinine levels; stage 2 demonstrated increased tryptophan and nitrogenous compounds with diminished uric acid; stage 3 displayed the highest neopterin and the lowest creatinine levels. We utilized the PLS-SVM model for discriminant analysis, achieving over 90% identification rate in distinguishing AKI patients, encompassing all stages, from non-AKI subjects.Conclusions This study characterizes the incidence and risk factors for AKI after cardiac surgery. The unique spectral information garnered from this study can also pave the way for developing an in vivo RS method to detect and monitor AKI effectively.

Background Hypertension and hypercholesterolemia are important risk factors for cardiovascular disease, and treatment with fixed‐dose combination (FDC) regimens is recommended by current guidelines. However, the clinical outcomes of different FDC dosages remain unknown. This study aimed to examine the clinical outcomes of FDC regimens and the free combination of amlodipine and atorvastatin at different dosages. Methods and Results Patients with concurrent hypertension and hypercholesterolemia treated daily with an FDC of 5 mg amlodipine and 10 mg atorvastatin (5/10 fixed group), and FDC of 5 mg amlodipine and 20 mg atorvastatin (5/20 fixed group), or free combination of 5 mg amlodipine and 20 mg atorvastatin (5/20 free group) were identified from the National Health Insurance Research Database of Taiwan. The primary outcome was the composite cardiovascular outcomes, including cardiovascular death, acute myocardial infarction, stroke, and coronary intervention. A total of 9095 patients were eligible for inclusion. The incidence of primary outcome per 1000 person‐years was 16.6 in the 5/10 fixed group, 12.6 in the 5/20 fixed group, and 16.5 in the 5/20 free group (5/20 fixed versus 5/20 free: hazard ratio [HR], 0.76 [95% CI, 0.64–0.91]; 5/20 fixed versus 5/10 fixed: HR, 0.76 [95% CI, 0.63–0.90]). Conclusions Among patients with concomitant hypertension and hypercholesterolemia, treatment with an FDC of amlodipine and high‐dose atorvastatin led to a lower risk of a composite of cardiovascular outcomes than treatment with the free combination or a similar FDC with a lower dose of atorvastatin.

Background Both high and low levels of serum potassium measurements are linked with a higher risk of adverse clinical events among patients with type 2 diabetes. The study was aimed at evaluating the implications of the various degrees of initial estimated glomerular filtration rate (eGFR) change on subsequent serum potassium homeostasis following sodium–glucose cotransporter‐2 inhibitor (SGLT2i) initiation among patients with type 2 diabetes. Methods and Results We used medical data from a multicenter health care provider in Taiwan and recruited 5529 patients with type 2 diabetes with baseline/follow‐up eGFR data available after 4 to 12 weeks of SGLT2i treatment from June 1, 2016, to December 31, 2018. SGLT2i treatment was associated with an initial mean (SEM) eGFR decline of −3.5 (0.2) mL/min per 1.73 m2 in overall study participants. A total of 36.7% (n=2028) of patients experienced no eGFR decline, and 57.9% (n=3201) and 5.4% (n=300) of patients experienced an eGFR decline of 0% to 30% and >30%, respectively. Patients with an initial eGFR decline of >30% were associated with higher variability in consequent serum potassium measurement when compared with those without an initial eGFR decline. Participants with a pronounced eGFR decline of >30% were associated with a higher risk of hyperkalemia ≥5.5 (adjusted hazard ratio,4.59 [95% CI, 2.28–9.26]) or use of potassium binder (adjusted hazard ratio, 2.65 [95% CI, 1.78–3.95]) as well as hypokalemia events

BackgroundRecently, there have been conflicting results reporting an increased risk of AR or MR associated with oral fluoroquinolones (FQs).This study investigated whether the use of FQs increases the risk of mitral regurgitation (MR) or aortic regurgitation (AR).MethodsA retrospective cohort study was conducted by using the Taiwan National Health Insurance research database. A unidirectional case-crossover design without selecting controls from an external population was adopted in this study. A total of 26,650 adult patients with new onset of AR or MR between January 1, 2000, and December 31, 2012, were identified. The risk of outcomes was compared between the hazard period and one of the randomly selected referent periods of the same individuals.ResultsBefore exclusion of pneumonia diagnosed within 2 months before the index date, patients who took FQs had a significantly greater risk of AR or MR (adjusted odds ratio [aOR] 1.51, 95% confidence interval [CI] 1.30-1.77), any AR (combined AR and MR) (aOR 1.50, 95% CI 1.10-2.04), and any MR (combined AR and MR) (aOR 1.37, 95% CI 1.16-1.62). After exclusion of pneumonia, FQs exposure remained significantly associated with a greater risk of MR (aOR 1.38, 95% CI 1.17-1.62) and any MR (aOR 1.25, 95% CI 1.05-1.48).ConclusionsThe findings suggested that patients treated with FQs could be warned about the potential risk for MR even after considering the possibility of protopathic bias. Reducing unnecessary FQs prescriptions may be considered to reduce the risk of valvular heart disease.

Background The widely used Bentall procedure is the criterion standard treatment for aortic root pathology. Studies comparing the long‐term outcomes of bioprosthetic and mechanical valves in patients undergoing the Bentall procedure are limited. Methods and Results Patients who underwent the Bentall procedure with a bioprosthetic or mechanical valve between 2001 and 2018 were identified from Taiwan's National Health Insurance Research Database. The primary outcome of interest was all‐cause mortality. Inverse probability of treatment weighting was performed to compare the 2 prosthetic types. In total, 1052 patients who underwent the Bentall procedure were identified. Among these patients, 351 (33.4%) and 701 (66.6%) chose bioprosthetic and mechanical valves, respectively. After inverse probability of treatment weighting, no significant differences in the in‐hospital mortality (odds ratio, 0.96 [95% CI, 0.77–1.19]; P=0.716) and all‐cause mortality (34.1% vs. 38.1%; hazard ratio, 0.90 [95% CI, 0.78–1.04]; P=0.154) were observed between the groups. The benefits of relative mortality associated with mechanical valves were apparent in younger patients and persisted until ≈50 years of age. Conclusions No differences in survival benefits were observed between the valves in patients who underwent the Bentall procedure. Additionally, bioprosthetic valves may be a reasonable choice for patients aged >50 years when receiving the Bentall procedure in this valve‐in‐valve era.

Abstract There is scarce evidence about the surgeon learning curve of acute type A aortic dissection surgery and whether the optimal procedure number exists when training a cardiovascular surgeon. A total of 704 patients with acute type A aortic dissection surgery performed by 17 junior surgeons who can identify their first career surgery from January 1, 2005, to December 31, 2018, are included. The surgeon experience volume is defined as the cumulative number of acute type A aortic dissection surgery of the surgeon since January 1, 2005. The primary outcome was in-hospital mortality. The possibility of non-linearity and cutoffs for surgeon experience volume level was explored using a restricted cubic spline model. The results revealed that more surgeon experience volume is significantly correlated to a lower in-hospital mortality rate (r = − 0.58, P = 0.010). The RCS model shows for an operator who reaches 25 cumulative volumes of acute type A aortic dissection surgery, the average in-hospital mortality rate of the patients can be below 10%. Furthermore, the longer duration from the 1st to 25th operations of the surgeon is significantly correlated to a higher average in-hospital mortality rate of the patients (r = 0.61, p = 0.045). Acute type A aortic dissection surgery has a prominent learning curve in terms of improving clinical outcomes. The findings suggest fostering high-volume surgeons at high-volume hospitals can achieve optimal clinical outcomes.

Abstract Background The impact of sex-related differences in patients receiving extracorporeal membrane oxygenation support (ECMO) support is still inconclusive. This population-based study aimed to investigate sex differences in short- or long-term outcomes in order to improve clinical practice. Methods Patients who received ECMO between 2001 to 2017 were identified from the Taiwan National Health Insurance Research Database. Propensity score matching with a 1:1 ratio was conducted in female-to-male groups, to reduce confounding of baseline covariates. Outcomes included in-hospital mortality, all-cause mortality, all-cause readmission, and ECMO-related complications. Logistic regression analysis, Cox proportional hazard model, and join point regression were used to compare sex differences in both short- or long-term outcomes. Results In total, 7,010 matched patients from 11,734 ECMO receivers were included for analysis. The use of ECMO increased dramatically in past years, although the proportion of females was still lower than males. There was a decreasing trend of females undergoing ECMO over time. Female patients have lower risks of in-hospital mortality (64.08% in females vs 66.48% in males; P = 0.0352) and ECMO-related complications compared with males. Furthermore, females also had favorable long-term late outcomes such as all-cause mortality (73.35% in females vs 76.98% in males; P = 0.009) and readmission rate (6.99% in females vs 9.19% in males; P = 0.001). Conclusions Female patients had more favorable in-hospital and long-term survival outcomes. Despite improvement in modern ECMO technique and equipment, ECMO remains underutilized in eligible female patients. Thus, females should undergo ECMO treatment if available and indicated. Trial registration The institutional review board of Chang Gung Memorial Hospital approved all data usage and the study protocol (registration number: 202100151B0C502; date of registration: 23/08/2021).

Background The risk of cardiac dysfunction for patients with prostate cancer undergoing androgen deprivation therapy (ADT) in the real‐world setting remains unclear. Methods and Results A total of 1120 patients with prostate cancer and a baseline echocardiography scan were identified from Chang Gung Research Database between January 1, 2001 and December 31, 2019. Patients were treated with gonadotropin‐releasing hormone agonist therapy, gonadotropin‐releasing hormone antagonist therapy, or bilateral orchiectomy. Changes in left ventricular ejection fraction (LVEF) were further assessed in 421 patients using repeated measurements of LVEF before and during ADT treatment. The incidence of cancer therapy–related cardiac dysfunction (CT‐RCD) was evaluated and defined as a ≥10% absolute decline in LVEF from baseline to a value of

Abstract Background Atrial fibrillation is the most common cardiac arrythmia and causes many complications. Sinus rhythm restoration could reduce late mortality of atrial fibrillation patients. The Maze procedure is the gold standard for surgical ablation of atrial fibrillation. Higher surgical volume has been documented with favorable outcomes of various cardiac procedures such as mitral valve surgery and aortic valve replacement. We aimed to determine the volume–outcome relationship (i.e., association between surgical volume and outcomes) for the concomitant Maze procedure during major cardiac surgeries. Methods This nationwide population-based cohort study retrieved data from the Taiwan National Health Insurance Research Database. Adult patients undergoing concomitant Maze procedures during 2010–2017 were identified; consequently, 2666 patients were classified into four subgroups based on hospital cumulative surgery volumes. In-hospital outcomes and late outcomes during follow-up were analyzed. Logistic regression and Cox proportional hazards model were used to analyze the volume–outcome relationship. Results Patients undergoing Maze procedures at lower-volume hospitals tended to be frailer and had higher comorbidity scores. Patients in the highest-volume hospitals had a lower risk of in-hospital mortality than those in the lowest-volume hospitals [adjusted odds ratio, 0.30; 95% confidence interval (CI), 0.15–0.61; P

Abstract Background Although a few meta-analyses were conducted to compare the risk of incident atrial fibrillation (AF) between sodium-glucose cotransporter-2 inhibitor (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and other anti-hyperglycemic agents using indirect or direct comparison, the above analyses showed conflicting results with each other. We aimed to evaluate the risk of new-onset AF associated with the use of SGLT2i, GLP-1RA, and dipeptidyl peptidase-4 inhibitor (DPP4i) among a large longitudinal cohort of diabetic patients. Methods In this nationwide retrospective cohort study based on the Taiwan National Health Insurance Research Database, a total of 344,893, 44,370, and 393,100 consecutive patients with type 2 diabetes without preexisting AF receiving GLP-1RA, SGLT2i, and DPP4i, respectively, were enrolled from May 1, 2016, to December 31, 2019. We used 1:1 propensity score matching (PSM) to balance covariates across paired study groups. Patients were followed from the drug index date until the occurrence of AF, death, discontinuation of the index drug, or the end of the study period (December 31, 2020), whichever occurred first. Results After PSM, there were 245,442, 43,682, and 39,190 paired cohorts of SGLT2i-DPP4i, SGLT2i-GLP-1RA, and GLP-1RA-DPP4i, respectively. SGLT2i treatment was associated with lower risk of new-onset AF in participants with type 2 diabetes compared with either DPP4i [hazard ratio (HR):0.90; 95% confidential interval (CI) 0.84–0.96; P = 0.0028] or GLP-1RA [HR 0.74; 95% CI 0.63–0.88; P = 0.0007] treatment after PSM. There was no difference in the risk of incident AF between GLP-1RA and DPP4i users [HR 1.01; 95% CI 0.86–1.19; P = 0.8980]. The above findings persisted among several important subgroups. Dapagliflozin was specifically associated with a lower risk of new-onset AF compared with DPP4i (P interaction = 0.02). Conclusions Compared with DPP4i, SGLT2i but not GLP-1RA was associated with a lower risk of incident AF in patients with type 2 diabetes.

Introduction: Acute kidney disease (AKD) represents a continuum of kidney injury for 7 to 90 days after acute kidney injury (AKI). The incidence and prognosis of AKD after acute decompensated heart failure (ADHF) are currently unclear. The aims of this study were to explore the incidence of AKD and the transition from AKI to AKD, to identify risk factors for AKD and develop a prediction model for any-stage AKD, and to evaluate the prognosis of AKD. Methods: A total of 7519 patients admitted for ADHF between January 1, 2008, and December 31, 2018, from a multi-institutional database were identified. The composite outcomes after ADHF were stage 3 AKD and all-cause death. The prognosis impact of AKD, including major adverse kidney events (MAKEs), all-cause death, and heart failure hospitalization (HFH), during 5 years of follow-up was analyzed. Results: The overall incidence of AKI and AKD after ADHF was 9% and 21.2%, respectively; 39.4% of the patients diagnosed with having AKI during ADHF subsequently developed AKD whereas 19.4% of the patients without an identified AKI episode subsequently developed AKD. The predictive scoring models revealed C-statistics of 0.726 (95% CI: 0.712–0.740) for any-stage AKD and 0.807 (95% CI: 0.793–0.821) for the composite of stage 3 AKD and death. Finally, AKD was associated with higher risks of all-cause death, MAKE, and HFH during the 5 years of follow-up (P < 0.001). Conclusion: AKD after ADHF are associated with adverse outcomes. Our model could help in identification of patients at risk for AKD development, especially in those who did not have an index AKI episode.

Abstract No study has evaluated the effect of dexmedetomidine in patients who received surgery for type A aortic dissection. This is the first study to evaluate the effect of dexmedetomidine in aortic dissection patients. This study was executed using data from the Chang Gung Research Database in Taiwan. The CGRD contains the multi‐institutional standardized electronic medical records from seven Chang Gung Memorial hospitals, the largest medical system in Taiwan. We retrospectively evaluate patients who received surgery for acute type A aortic dissection between January 2014 and December 2018. Overall, 511 patients were included, of whom 104 has received dexmedetomidine infusion in the postoperative period. One-to-two propensity score-matching yielded 86 cases in the dexmedetomidine group and 158 cases in the non-dexmedetomidine group. The in-hospital mortality and composite outcome including all-cause mortality, acute kidney injury, delirium, postoperative atrial fibrillation, and respiratory failure, were considered primary outcomes. The in-hospital mortality and composite outcome were similar between groups. The risk of Acute Kidney Injury Network stage 3 acute kidney injury was significantly lower in the dexmedetomidine group than in the non-dexmedetomidine group (8.1% vs 19.0%; OR, 0.38; 95% CI, 0.17–0.86; p = 0.020. The risk of newly-onset dialysis was also significantly lower in the dexmedetomidine group than in the non-dexmedetomidine group (4.7% vs 13.3%; OR, 0.32; 95% CI, 0.11–0.90; p = 0.031). Post-operative dexmedetomidine infusion significantly reduced the rate of severe acute kidney injury and newly-onset dialysis in patients who received surgery for acute type A aortic dissection.

Abstract Objective This study assesses the mortality outcomes of non‐vitamin K antagonist oral anticoagulants (NOACs) in cancer patients with venous thromboembolism (VTE) and atrial fibrillation (AF). Methods Medical records of cancer patients receiving NOACs for VTE or AF between January 1, 2011, and December 31, 2016, were retrieved from Taiwan's National Health Institute Research Database. NOACs were compared using the inverse probability of treatment weighting (IPTW) method. The primary outcome was cancer‐related death. Secondary outcomes were all‐cause mortality, major bleeding, and gastrointestinal (GI) bleeding. Results Among 202,754 patients who received anticoagulants, 3591 patients (dabigatran: 907; rivaroxaban: 2684) with active cancers were studied. Patients who received dabigatran were associated with lower risks of cancer‐related death at one year (HR = 0.71, 95% CI = 0.54–0.93) and at the end of follow‐ups (HR = 0.79, 95% CI = 0.64–0.98) compared with rivaroxaban. Patients who received dabigatran were also associated with lower risks of all‐cause mortality (HR = 0.81, 95% CI = 0.67–0.97), major bleeding (HR = 0.64, 95% CI = 0.47–0.88), and GI bleeding (HR = 0.57, 95% CI = 0.39–0.84) at the end of follow‐ups compared with rivaroxaban. Conclusion Compared with rivaroxaban, the use of dabigatran may be associated with a lower risk of cancer‐related death and all‐cause mortality.

ObjectsCardiac surgery is associated with acute kidney injury (AKI). However, the effects of various pharmacological and non-pharmacological strategies for AKI prevention have not been thoroughly investigated, and their effectiveness in preventing AKI-related adverse outcomes has not been systematically evaluated.MethodsStudies from PubMed, Embase, and Medline and registered trials from published through December 2021 that evaluated strategies for preventing post–cardiac surgery AKI were identified. The effectiveness of these strategies was assessed through a network meta-analysis (NMA). The secondary outcomes were prevention of dialysis-requiring AKI, mortality, intensive care unit (ICU) length of stay (LOS), and hospital LOS. The interventions were ranked using the P-score method. Confidence in the results of the NMA was assessed using the Confidence in NMA (CINeMA) framework.ResultsA total of 161 trials (involving 46,619 participants) and 53 strategies were identified. Eight pharmacological strategies {natriuretic peptides [odds ratio (OR): 0.30, 95% confidence interval (CI): 0.19–0.47], nitroprusside [OR: 0.29, 95% CI: 0.12–0.68], fenoldopam [OR: 0.36, 95% CI: 0.17–0.76], tolvaptan [OR: 0.35, 95% CI: 0.14–0.90], N-acetyl cysteine with carvedilol [OR: 0.37, 95% CI: 0.16–0.85], dexmedetomidine [OR: 0.49, 95% CI: 0.32–0.76;], levosimendan [OR: 0.56, 95% CI: 0.37–0.84], and erythropoietin [OR: 0.62, 95% CI: 0.41–0.94]} and one non-pharmacological intervention (remote ischemic preconditioning, OR: 0.76, 95% CI: 0.63–0.92) were associated with a lower incidence of post–cardiac surgery AKI with moderate to low confidence. Among these nine strategies, five (fenoldopam, erythropoietin, natriuretic peptides, levosimendan, and remote ischemic preconditioning) were associated with a shorter ICU LOS, and two (natriuretic peptides [OR: 0.30, 95% CI: 0.15–0.60] and levosimendan [OR: 0.68, 95% CI: 0.49–0.95]) were associated with a lower incidence of dialysis-requiring AKI. Natriuretic peptides were also associated with a lower risk of mortality (OR: 0.50, 95% CI: 0.29–0.86). The results of a sensitivity analysis support the robustness and effectiveness of natriuretic peptides and dexmedetomidine.ConclusionNine potentially effective strategies were identified. Natriuretic peptide therapy was the most effective pharmacological strategy, and remote ischemic preconditioning was the only effective non-pharmacological strategy. Preventive strategies might also help prevent AKI-related adverse outcomes. Additional studies are required to explore the optimal dosages and protocols for potentially effective AKI prevention strategies.

BackgroundSodium-glucose co-transporter 2 (SGLT2) inhibitors has been shown with cardiovascular benefit in type 2 diabetes mellitus (T2DM) patients. However, its osmotic diuresis still concern physicians who may look for possible electrolyte imbalance. We therefore aimed to investigate electrocardiographic (ECG) changes associated with SGLT2 inhibitors.MethodsElectronic medical records from Chang Gung Research Database between January 1, 2001 and January 31, 2019 were searched for patients with ECG reports and patients on an oral hypoglycemic agent (OHA). We then separate these T2DM patients with EKG into those taking either SGLT2 inhibitors or non-SGLT2 inhibitors. We excluded patients with OHA use 500 ms, and ECG showing atrial fibrillation or atrial flutter. Propensity score matching (PSM) was performed between groups by age, sex, comorbidities, and medications (including QT prolonging medications). Conditional logistic regression and Firth's logistic regression for rare events were employed to compare the difference between SGLT2 and non-SGLT2 inhibitor patients.ResultsAfter exclusion criteria and PSM, there remained 1,056 patients with ECG on SGLT2 inhibitors and 2,119 patients with ECG on non-SGLT2 inhibitors in the study. There were no differences in PR intervals, QT prolongations by Bazett's or Fridericia's formulas, new onset ST-T changes, new onset CRBBB or CLBBB, and ventricular arrhythmia between the group of patients on SGLT2 inhibitors and the group of patients on non-SGLT2 inhibitors. There were no differences between the two groups in terms of cardiovascular death and sudden cardiac death. In addition, there were no differences between the two groups in terms of electrolytes.ConclusionsCompared with T2DM patients on non-SGLT2 inhibitors, there were no differences in PR interval, QT interval, ST-T changes, bundle-branch block, or ventricular arrhythmia in the patients on SGLT2 inhibitors. There were no differences in cardiovascular mortality between these two groups. In addition, there were no electrolyte differences between groups. SGLT2 inhibitors appeared to be well-tolerated in terms of cardiovascular safety.

Abstract Background There is a controversy over the association between obesity and the risk of renal events in patients with type 2 diabetes mellitus (T2DM). Furthermore, whether body weight (BW) loss following sodium glucose cotransporter 2 inhibitor (SGLT2i) treatment associated with risk of adverse renal events is unknown. Methods We used medical data from a multi-center healthcare provider in Taiwan, enrolling 8992 T2DM patients with a baseline/following-up BW data available after around 12 weeks of SGLT2i treatment, from June 1, 2016 to December 31, 2018. Patients were followed up until the occurrence of composite renal outcome (estimated glomerular filtration rate decline > 40% or end-stage kidney disease) or the end of study period, whichever occurred first. Results Participants were divided into six baseline BMI categories:

Abstract Background Sodium–glucose cotransporter 2 inhibitor (SGLT2i) use reduces body weight (BW) in patients with type 2 diabetes mellitus (T2DM). Obesity and T2DM are strong risk factors of new-onset atrial fibrillation (AF). However, whether BW loss following SGLT2i treatment reduces AF risk in patients with T2DM remains unclear. Methods We used a medical database from a multicenter health care provider in Taiwan, which included 10,237 patients with T2DM, from June 1, 2016 to December 31, 2018, whose BW data at baseline and at 12 weeks of SGLT2i treatment were available. Patients were followed up from the drug index date until the occurrence of new-onset AF, discontinuation of the SGLT2i, or the end of the study period, whichever occurred first. Results The patients’ baseline body mass index (BMI) was 28.08 $$\pm$$ ± 4.88 kg/m2. SGLT2i treatment was associated with a BW loss of 1.35 $$\pm$$ ± 3.28 kg (1.78% $$\pm$$ ± 4.47%). There were 37.4%, 47.0%, and 15.6% of patients experienced no-BW loss (n = 3832), BW loss 0.0–4.9% (n = 4814), and $$\ge$$ ≥ 5.0% (n = 1591) following SGLT2i treatment, respectively. Compared with patients with baseline BMI 0.05). Conclusion BW loss of ≥ 5.0% following SGLT2i treatment was associated with a lower risk of new-onset AF in patients with T2DM in real-world practice.

Abstract Background Sodium-glucose co-transporter 2 inhibitors (SGLT2i) has shown evidence of cardiovascular benefit in patients with type 2 diabetes mellitus (T2DM). Currently metformin is the guideline-recommended first-line treatment. We aimed to investigate the benefit of SGLT2i vs metformin as first-line therapy. Methods Electronic medical records from Chang Gung Research Database during 2016–2019 were retrieved for patients with T2DM. Patients aged

Abstract Background Sodium glucose cotransporter 2 inhibitor (SGLT2i) reduces the risk of hard cardiovascular endpoints in type 2 diabetes mellitus (T2DM) patients with/without established cardiovascular diseases. Whether SGLT2i is associated with a lower risk of new-onset atrial fibrillation (AF) in T2DM patients is unclear. We aimed to evaluate the risk of new-onset AF associated with the use of SGLT2i compared to dipeptidyl peptidase-4 inhibitor (DPP4i) among a longitudinal cohort of diabetic patients. Methods We used medical data from a multi-center healthcare provider in Taiwan, which included a total of 15,606 and 12,383 patients treated with SGLT2i and DPP4i, respectively, from June 1, 2016 to December 31, 2018. We used propensity-score weighting to balance covariates across study groups. Patients were followed up from the drug index date until the occurrence of new-onset AF, discontinuation of the index drug, or the end of the study period, whichever occurred first. Results Overall, 55%, 45%, and 0% of the patients were treated with empagliflozin, dapagliflozin, and canagliflozin, respectively. Most patients in the DPP4i group were prescribed with linagliptin (51%), followed by sitagliptin (24%), saxagliptin (13%), vildagliptin (8%) and alogliptin (5%). The use of SGLT2i was associated with a lower risk of new-onset AF compared with DPP4i after propensity-score weighting [hazard ratio: 0.61; 95% confidential interval: 0.50–0.73; P

Abstract Aims Patients with concomitant atrial fibrillation (AF) and reduced left ventricular ejection fraction (LVEF) have poor prognosis. Outcomes of novel oral anticoagulant (NOAC) in elderly AF patients with normal, mid‐range, and reduced LVEF were investigated. Methods and results Data were retrieved from Chang Gung Research Database during 2010–2017 for patients with AF. We excluded patients with venous thromboembolism within 6 months, total knee/hip replacement and heart valve replacement within 6 months, end‐stage renal disease, stroke/systemic embolism (SE)/death within 7 days, age

Abstract Background Rattus norvegicus and Suncus murinus are important reservoirs of zoonotic bacterial diseases. An understanding of the composition of gut and oropharynx bacteria in these animals is important for monitoring and preventing such diseases. We therefore examined gut and oropharynx bacterial composition in these animals in China. Results Proteobacteria, Firmicutes and Bacteroidetes were the most abundant phyla in faecal and throat swab samples of both animals. However, the composition of the bacterial community differed significantly between sample types and animal species. Firmicutes exhibited the highest relative abundance in throat swab samples of R. norvegicus, followed by Proteobacteria and Bacteroidetes. In throat swab specimens of S. murinus, Proteobacteria was the predominant phylum, followed by Firmicutes and Bacteroidetes. Firmicutes showed the highest relative abundance in faecal specimens of R. norvegicus, followed by Bacteroidetes and Proteobacteria. Firmicutes and Proteobacteria had almost equal abundance in faecal specimens of S. murinus, with Bacteroidetes accounting for only 3.07%. The family Streptococcaceae was most common in throat swab samples of R. norvegicus, while Prevotellaceae was most common in its faecal samples. Pseudomonadaceae was the predominant family in throat swab samples of S. murinus, while Enterobacteriaceae was most common in faecal samples. We annotated 33.28% sequences from faecal samples of S. murinus as potential human pathogenic bacteria, approximately 3.06-fold those in R. norvegicus. Potential pathogenic bacteria annotated in throat swab samples of S. murinus were 1.35-fold those in R. norvegicus. Conclusions Bacterial composition of throat swabs and faecal samples from R. norvegicus differed from those of S. murinus. Both species carried various pathogenic bacteria, therefore both should be closely monitored in the future, especially for S. murinus.

Abstract 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

ObjectivesFor the endovascular intervention of acute ischemic stroke, a transcervical route is an alternative approach in patients with challenging anatomical variations. Percutaneous puncture is a common way, but it can cause many fatal complications. Direct carotid artery exposure is an alternative for reducing complications. We demonstrate a technique of direct carotid exposure in patients for whom transfemoral or transbrachial approaches were impossible. We present patient outcomes and discuss the indications and limitations of this procedure.MethodsWe retrospectively reviewed the cases of patients undergoing direct carotid exposure for acute ischemic stroke in a hybrid angiography suite and presented the details of the technique.ResultsAmong 548 consecutive patients with acute large vessel strokes who were treated by emergency endovascular thrombectomy or stenting between January 2015 and September 2020 in our center, only 8 (1.46%) required a transcervical approach. Of them, 7 underwent direct carotid exposure with successful recanalization and good clinical outcomes.ConclusionsDirect carotid exposure for endovascular stroke treatment is effective and advantageous in patients with challenging anatomical variations. Performing this procedure in carefully selected patients in the hybrid angiography suite can be beneficial in terms of open surgeries, saving time, and decreasing the risk of postoperative complications.

ObjectiveThe aim of this study is to evaluate the sex-related differences on the risks of perioperative and late outcomes for adult acute aortic dissection (AAD) patients following surgical management.Methods and resultsBy using Taiwan National Health Insurance Research Database, totally 1,410 female and 3,432 male patients were identified to first-ever receive type A AAD open surgery or type B AAD stenting treatment from 2004 to 2013. We assessed the sex-related difference on outcomes, including in-hospital mortality, all-cause mortality, aortic death, redo aortic surgery, ischemic stroke, and depression during the follow-up period. The analysis was done separately for type A and type B surgeries.ResultsOn average, female patients diagnosed with AAD were older than males. There was no significant sex difference of in-hospital mortality or all-cause mortality for both type A open and type B stent surgeries. The risk of redo aortic surgery was significantly greater in males than females (7.8% vs. 4%; unadjusted subdistribution hazard ratio [SHR] 0.51, 95% CI 0.38-0.69) for type A open surgery, but not for type B stent surgery. Noticeably, the risk of newly-diagnosed depression was significantly greater in females than males (8% vs. 5.1%; unadjusted SHR 1.6, 95% CI 1.24-2.06) for type A open surgery, but not for type B stent surgery.ConclusionsNo significant sex-related difference was found for the in-hospital mortality or accumulative all-cause mortality. However, there were more redo aortic surgeries for males and more postoperative depression for females in type A AAD population.

Background: The effectiveness and safety of initiating sacubitril/valsartan therapy among patients who are hospitalized for acute heart failure (HF) is unclear. Methods: A cohort of 3736 patients with HF with reduced ejection fraction (HFrEF) hospitalized for acute HF was identified from Chang Gung Research Database between January 1, 2016 and August 31, 2019. The risks of rehospitalization for HF and death associated with sacubitril/valsartan therapy compared to angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) therapy were evaluated. We used stabilized inverse probability of treatment weighting to balance the baseline covariates. The risks of fatal and non-fatal outcomes between the groups were compared using a Cox proportional hazard model and Fine and Gray subdistribution hazard model, respectively. Findings: The composite of rehospitalization for HF and death occurred in 22.9% of the patients in the sacubitril/valsartan group compared to 32.6% in the ACEI/ARB group (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.52–0.97) after a mean follow-up period of 11.8 months. The sacubitril/valsartan group had a lower risk of rehospitalization for HF (subdistribution HR 0.83, 95% CI 0.74–0.92) and all-cause death (HR 0.51, 95% CI 0.27–0.94). There were no significant differences in the rates of worsening renal function or severe hyperkalemia between the two groups. Interpretation: In real-world practice, initiating sacubitril/valsartan therapy among patients with HFrEF who were hospitalized for acute HF was associated with a lower rate of rehospitalization for HF and death compared with ACEI/ARB therapy. Funding: This study was supported by Novartis Pharmaceuticals.

Background: The prevalence of high serum uric acid is increasingly rising in recent years, and diet behavior is perceived to be associated with it. This study aimed to explore the relationship between eating away from home (EAFH) and the risk of high serum uric acid in adults in South China.Methods: The data utilized in this study were from Guangdong Nutrition and Health Survey (NHS) 2015. Serum uric acid concentration was detected. EAFH in the past week was investigated. We defined EAFH as food consumption away from home. Dietary data were collected by 24-h recalls on 3 consecutive days. A generalized linear mixed-effects model was applied to compute the odds ratio (OR) and its corresponding 95% CI.Results: A total of 3,489 individuals were included in this study. A 1.27-fold OR (95% CI: 1.05–1.52, P = 0.012) of high serum uric acid was identified in adults with EAFH in comparison with those without EAFH. With respect to men, a 1.66-fold OR (95% CI: 1.3–2.1, P < 0.001) of high serum uric acid was observed. We also observed that men with EAFH had higher intakes of red meat, poultry, vegetable, carbohydrate, protein, fat, and total energy, while a lower grain intake than those without EAFH. However, there was a lack of significant association between EAFH and the odds ratio of high serum uric acid in women. Women with EAFH did not have higher consumptions of red meat, vegetable, fish, fat, and water than those without EAFH.Conclusions: This study found that EAFH was associated with an increased odds ratio of high serum uric acid in men, but not in women.

Background: Gestational hypertension and preeclampsia are hypertensive disorders related to pregnancy that can cause maternal morbidity and fetal growth retardation. The association of these disorders with family history remains unclear. Objectives: To examine the degree of family aggregation of preeclampsia and gestational hypertension in Taiwan. Methods: The study was conducted using the data from the National Health Insurance Database of Taiwan. Delivery events in Taiwan from 1999 to 2013 were collected. Preeclampsia was identified based on the hospital diagnosis of index delivery. The family aggregation pattern of preeclampsia was assessed and analyzed using the relationship registered in the database with the patients. Results: A total of 60,314 preeclampsia events were identified among 4,091,641 deliveries, accounting for 1.5% of the cohort. The incidence of preeclampsia increased with maternal age. A total of 768 preeclampsia events occurred in mothers who had a sororal history of preeclampsia (n = 20,704), accounting for 1.3% of all preeclampsia events (n = 60,314). Mothers who had a sororal history of preeclampsia had a relative risk (RR) of 2.6 (95% confidence interval [CI]: 2.41–2.80) for preeclampsia compared with mothers who did not have a sororal history of preeclampsia. The RR for gestational hypertension was 2.79 (95% CI: 2.36–3.3) in mothers with a positive sororal history of gestational hypertension. Conclusions: Having a sororal history of preeclampsia was a strong risk factor for preeclampsia and gestational hypertension in mothers in Taiwan. The pattern of family aggregation was similar at all maternal ages.

Background Benefits of patients with end‐stage renal disease and atrial fibrillation undergoing peritoneal dialysis (PD) or hemodialysis are unknown. Methods and Results Patients undergoing dialysis were retrieved from Taiwan National Health Insurance Research Database during 2001 to 2013 and separated into PD or hemodialysis. Primary outcomes were ischemic stroke/systemic embolism, major bleeding, and intracranial hemorrhage (ICH). An inverse probability of treatment weighting based on propensity score was used to reduce the confounding. The risk of outcomes between PD and hemodialysis was compared using Cox proportional hazard model for fatal outcomes or Fine and Gray subdistribution hazard model which considered death a competing risk, respectively. A total of 7916 patients with end‐stage renal disease with atrial fibrillation undergoing PD or hemodialysis during 2001 to 2013 were identified. After exclusion criteria, 363 patients receiving PD and 5302 patients receiving hemodialysis were analyzed. At 1‐year follow‐up, the risk of ICH was significantly lower in the PD group compared with the hemodialysis group (0.2% versus 0.9%; subdistribution hazard ratio [SHR], 0.31; 95% CI, 0.17–0.57). At 3‐year follow‐up, the risks of major bleeding and ICH were significantly lower in the PD group compared with the hemodialysis group (major bleeding: 1.8% versus 3.2%; SHR, 0.68; 95% CI, 0.53–0.87; ICH: 0.5% versus 2%; SHR, 0.32; 95% CI, 0.21–0.48). At 5‐year follow‐up, ischemic stroke/systemic embolism, major bleeding, and ICH were significantly lower in the PD group compared with the hemodialysis group (ischemic stroke/systemic embolism: 12.4% versus 17.7%, SHR, 0.87; 95% CI, 0.79–0.96; major bleeding: 2.6% versus 4.1%; SHR, 0.79; 95% CI, 0.64–0.97; ICH: 0.5% versus 2.6%; SHR, 0.25; 95% CI, 0.17–0.37). Conclusions In patients with end‐stage renal disease and atrial fibrillation, dialytic modalities by PD or hemodialysis impacted these patients differently. There were overall reduced ischemic stroke/systemic embolism, major bleeding, and ICH at 5‐year follow‐up in patients undergoing PD compared with hemodialysis.

Abstract Background Higher dietary acid load (DAL) was considered to be associated with an elevated risk of hypertension, while related data from mainland China remains scarce and incomplete. We aim to evaluate the association between DAL and the risk of hypertension among adults from South China. Methods We conducted a nutrition and health survey in Guangdong Province located in southern China from 2015 to 2017. A four-stage probability sampling method was utilized to select representative samples of citizens aged ≥18 years old. DAL was assessed by potential renal acid load (PRAL) and net endogenous acid production (NEAP). Participants were divided to 4 groups (Q1-Q4) according to the quartile points of PRAL or NEAP distributions. Generalized linear mixed effects models were applied to evaluate the association between DAL and the risk of hypertension. Results A total of 3501 individuals were eligible for this study and 45.9% was male participants. Hypertension rate was 30.7%. A higher PRAL was associated with higher prevalence rate of hypertension among the male (P-trend = 0.03). OR for Q2 was 1.34 (95%CI, 0.94–1.91), Q3 was 1.53 (95%CI = 1.08, 2.16) and Q4 was 1.51 (95%CI, 1.08–2.16) among the male. However, as for total participants, the female, the participants with ≤55 years or participants with > 55 years, the associations were lack of significance. With respect to association between NEAP and hypertension, non-significant results were identified. Conclusions The current study indicated male hypertension was associated with higher PRAL, while given to this study was cross-sectional design, further studies are warranted to verify the association.

Abstract Background No study has specifically investigated the duration of continuous renal replacement therapy (CRRT) in patients who experienced acute kidney injury during extracorporeal membrane oxygenation (ECMO) support. However, there are concerns that prolonged CRRT may be futile. Methods We conducted a retrospective population-based cohort study using Taiwan National Health Insurance Research Database data collected between January 1, 2007 and December 31, 2013. Patients who received ECMO and CRRT during the study period were included. We divided patients into three groups based on the duration of CRRT received: ≤ 3 days, 4–6 days, and ≥ 7 days. The outcomes were all-cause mortality, end-stage renal disease, ventilator dependency, and readmission rate. Results There were 247, 134 and 187 patients who survived the hospitalization in the CRRT for ≤3 days, 4–6 days and > 7 days respectively. Survival after discharge did not differ significantly between CRRT for 4–6 days vs. ≤ 3 days (adjusted hazard ratio [aHR] 1.16, 95% confidence interval [CI] 0.85–1.57), between CRRT for > 7 days vs. ≤ 3 days (aHR 1.001, 95% CI 0.73–1.38) and between CRRT for > 7 days vs. 4–6 days (aHR 0.87, 95% CI 0.62–1.22). The patients who received CRRT for ≥7 days had a higher risk of ESRD than did those who received CRRT for ≤3 days (adjusted hazard ratio [aHR] 3.46, 95% confidence interval [CI] 1.47–8.14) and for 4–6 days (aHR 3.10, 95% CI 1.03–9.29). The incidence of ventilator dependence was higher in the patients with CRRT ≥7 days than in those with ≤3 days (aHR 2.45, 95% CI 1.32–4.54). The CRRT ≥7 days group also exhibited a higher readmission rate than did the 4–6 days and ≤ 3 days groups (aHR 1.43, 95% CI 1.04–1.96 and aHR 1.67, 95% CI 1.13–2.47, respectively). Conclusions Our study found similar long-term survival but increased ESRD and ventilator dependency among ECMO patients who underwent CRRT for ≥7 days. These results offer reason to be concerned that this aggressive life support may maintain patient survival but do so at the cost of long-term disabilities and a lower quality of life.

Abstract Background The long-term treatment trends of splenic injuries can provide guidance when treating trauma patients. The nonoperative management (NOM) of splenic injuries was introduced in early 1989. After decades of development, it has proven to be safe and is now the primary treatment choice worldwide. However, there remains a lack of nationwide registry data to support the feasibility and efficiency of NOM. Methods We used the Taiwan National Health Insurance Research Database to conduct a whole population-based cohort study. Patients admitted with blunt splenic injuries from 2002 to 2013 were identified. Demographic data, management methods, associated injuries, comorbidities and outcome parameters were collected. Patients were divided into 2 groups by the type of admitting institution: a tertiary center or a non-center hospital. We also used 4 years as an interval to analyze the changes in epidemiological data and treatment trends. Comparisons of the results of NOM and surgical management were also performed. Results A total of 12,455 patients were admitted with blunt splenic injuries between 2002 and 2013. Among the 11,551 patients treated in a single hospital after admission, patients underwent NOM more frequently at tertiary centers than at non-center hospitals (64.6% vs 50.3%). During the 12-year study period, the NOM rate increased from 56 to 73% in tertiary centers, while in noncenter hospitals, the rate only increased from 43 to 58%. The mortality rate decreased in tertiary centers from 8.9 to 7.2%, with no apparent change in noncenter hospitals. Complications occurred more frequently in the surgical management group. Conclusion There is a trend toward the use of NOM for blunt splenic injury treatments, and the outcomes from the NOM groups were not inferior to those of the operation group. In addition, tertiary centers performed more NOM than did non-center hospitals and better met the international consensus.

Background Dialysis‐requiring acute kidney injury (D‐AKI) is a major complication of cardiovascular surgery that results in worse prognosis. However, the incidence and impacts of D‐AKI in different types of cardiac surgeries have not been fully investigated. Methods and Results Patients admitted for cardiovascular surgery between July 1, 2004, and December 31, 2013, were identified from the National Health Insurance Research Database of Taiwan. The patients were grouped into D‐AKI (n=3089) and non–D‐AKI (n=42 151) groups. The outcome was all‐cause mortality and major adverse kidney event. The long‐term outcomes were worse in the D‐AKI group than the non–D‐AKI group (hazard ratio [HR], 3.89; 95% CI, 3.79–3.99 for major adverse kidney event; HR, 2.89; 95% CI, 2.81–2.98 for all‐cause mortality). Patients who underwent aortic surgery had higher risk for D‐AKI than other types of surgeries, but they were also more likely to recover. The long‐term dialysis rate for the patients who recovered from D‐AKI was also lowest in those who underwent aortic surgery. Among all types of cardiac surgeries with D‐AKI, patients who had heart valve surgery exhibited the greatest risks of all‐cause mortality (HR, 6.04; 95% CI, 5.78–6.32). Conclusions Compared with other heart surgeries, aortic surgery resulted in a higher incidence of D‐AKI but better renal recovery, better short‐term outcome, and lower incidences of long‐term dialysis.

ObjectiveSeveral serum biomarkers have been investigated for their potential as diagnostic tools in aortic disease; however, no study has investigated the association between serum biomarkers and outcomes after aortic surgery. This study explored the predictive ability of serum soluble lumican in postoperative outcomes after aortic surgery.MethodsIn total, 58 patients receiving aortic surgery for aortic dissection or aneurysm at Linkou Chang Gung Memorial Hospital in Taiwan in December 2011-September 2018 were enrolled. Blood samples were collected immediately upon patients' arrival in the intensive care unit after aortic surgery. The diagnostic properties of soluble lumican levels were assessed by performing receiver operating characteristic (ROC) curve analysis. The confidence interval (CI) of the area under the ROC curve (AUC) was measured using DeLong's nonparametric method and the optimal cutoff was determined using the Youden index.ResultsThe serum soluble lumican level distinguished prolonged ventilation (AUC, 73.5%; 95% CI, 57.7%-89.3%) and hospital stay for >30 days (AUC, 78.2%; 95% CI, 61.6%-94.7%). The optimal cutoffs of prolonged ventilation and hospital stay for >30 days were 1.547 and 5.992 ng/mL, respectively. The sensitivity and specificity were respectively 100% (95% CI, 71.5%-100%) and 40.4% (95% CI, 26.4%-55.7%) for prolonged ventilation and 58% (95% 27.7%-84.8%) and 91.3% (95% CI, 79.2%-97.6%) for hospital stay for >30 days.ConclusionsThe serum soluble lumican level can be a potential prognostic factor for predicting poor postoperative outcomes after aortic surgery. However, more studies are warranted in the future.

IntroductionAortic dissection (AD) is a life-threatening emergency, and lumican (LUM) is a potential Biomarker for AD diagnosis. We investigated LUM expression patterns in patients with AD and explored the molecular functions of Lum in AD mice model.MethodsLUM expression patterns were analyzed using aortic tissues of AD patients, and serum soluble LUM (s-LUM) levels were compared between patients with acute AD (AAD) and chronic AD (CAD). Lum-knockout (Lum-/-) mice were challenged with β-aminopropionitrile (BAPN) and angiotensin II (Ang II) to induce AD. The survival rate, AD incidence, and aortic aneurysm (AA) in these mice were compared with those in BAPN-Ang II-challenged wildtype (WT) mice. Tgf-β/Smad2, Mmps, Lum, and Nox expression patterns were examined.ResultsLUM expression was detected in the intima and media of the ascending aorta in patients with AAD. Serum s-LUM levels were significantly higher in patients with AAD than CAD. Furthermore, AD-associated mortality and thoracic aortic rupture incidence were significantly higher in the Lum-/- AD mice than in the WT AD mice. However, no significant pathologic changes in AA were observed in the Lum-/- AD mice compared with the WT AD mice. The BAPN-Ang II-challenged WT and Lum-/- AD mice had higher Tgf-β, p-Smad2, Mmp2, Mmp9, and Nox4 levels than those of non-AD mice. We also found that Lum expression was significantly higher in the BAPN-Ang II-challenged WT in comparison to the unchallenged WT mice.ConclusionLUM expression was altered in patients with AD display increased s-LUM in blood, and Lum-/- mice exhibited augmented AD pathogenesis. These findings support the notion that LUM is a biomarker signifying the pathogenesis of injured aorta seen in AAD. The presence of LUM is essential for maintenance of connective tissue integrity. Future studies should elucidate the mechanisms underlying LUM association in aortic changes.

Background Octogenarians (≥80 years old) are high‐risk patients for acute aortic dissection (AAD) surgery. However, no population‐based study has investigated the late outcomes of AAD surgery in octogenarians. This study aimed to investigate the late outcomes of AAD surgery in octogenarians. Methods and Results A total of 3998 patients who received AAD surgery from 2005 to 2013 were identified from the Taiwan National Health Insurance Research Database. In‐hospital complications and late outcomes including all‐cause mortality, major adverse cardiac and cerebrovascular event, respiratory failure, and redo aortic surgery were evaluated. The risks of late outcomes between octogenarians and nonoctogenarians were compared using the multivariable Cox proportional hazard model or Fine and Gray competing model. The numbers of the octogenarians who underwent type A and B AAD surgeries were 206 (6%; 206/3423) and 79 (13.7%; 79/575), respectively. Compared with the nonoctogenarians, the type A octogenarians had higher risks of in‐hospital mortality and several in‐hospital complications, whereas the type B octogenarians did not. Furthermore, compared with the nonoctogenarians, the type A octogenarians had a higher risk of all‐cause mortality (61.7% vs 32.5%; hazard ratio [HR], 2.35; 95% CI, 1.95–2.84) and a higher cumulative incidence of major adverse cardiac and cerebrovascular event and respiratory failure, and the type B octogenarians demonstrated a higher risk of all‐cause mortality (44.3% vs 30.4%; HR, 1.74; 95% CI, 1.18–2.55). The octogenarians receiving AAD surgeries had higher mortality rates than the normal octogenarian population. Conclusions Octogenarians receiving AAD surgeries exhibit worse late outcomes than nonoctogenarian counterparts.

Objectives Bleeding is a common problem during adult extracorporeal membranes oxygenation (ECMO) support, requiring blood transfusion for correction of volume depletion and coagulopathy. The goal of this study is to investigate the long-term outcomes for adults under support of ECMO with massive blood transfusion (MBT).Design Retrospective nationwide cohort study.Setting Data were provided from Taiwan National Health Insurance Research Database (NHIRD).Participants and interventions Totally 2757 adult patients were identified to receive MBT (red blood cell ≥10 units) during ECMO support from 2000 to 2013 via Taiwan NHIRD.Main outcome measures The outcomes included in-hospital major complications/mortality, all-cause mortality, cardiovascular death, newly onset end-stage renal disease and respiratory failure during the follow-up period.Results Patients with MBT had higher in-hospital mortality (65.6% vs 52.1%; OR 1.74; 95% CI 1.53 to 1.98) and all-cause mortality during the follow-up (47.0% vs 35.8%; HR 1.46; 95% CI 1.25 to 1.71) than those without MBT. Not only higher incidences of post ECMO sepsis, respiratory failure and acute kidney injury, but also longer duration of ECMO support, ventilator use and intensive care unit stay were demonstrated in the MBT group. Moreover, a subdistribution hazard model presented higher cumulative of respiratory failure (19.8% vs 16.2%; subdistribution HR 1.36; 95% CI 1.07 to 1.73) for the MBT cohort. Positive dose–dependent relationship was found between the amount of transfused red blood cell product and in-hospital mortality. In the MBT subgroup analysis for the impact of transfused ratio (fresh frozen plasma/packed red blood cell) on in-hospital mortality, ratio ≥1.0 had higher mortality.Conclusions Patients with MBT during ECMO support had worse long-term outcomes than non-MBT population. The transfused amount of red blood cell had positive dose–dependent effect on in-hospital mortality.

Background The transfemoral route is contraindicated in nearly 10% of transcatheter aortic valve replacement (TAVR) candidates because of unsuitable iliofemoral vessels. Transaxillary (TAx) and direct aortic (DAo) routes are the principal nonfemoral TAVR routes; however, few studies have compared their outcomes. Methods We performed a systematic review and meta-analysis to compare the rates of mortality, stroke, and other adverse events of TAx and DAo TAVR. The study was prospectively registered with PROSPERO (registration number: CRD42017069788). We searched Medline, PubMed, Embase, and Cochrane databases for studies reporting the outcomes of DAo or TAx TAVR in at least 10 patients. Studies that did not use the Valve Academic Research Consortium definitions were excluded. We included studies that did not directly compare the two approaches and then pooled rates of events from the included studies for comparison. Results In total, 31 studies were included in the quantitative meta-analysis, with 2,883 and 2,172 patients in the DAo and TAx TAVR groups, respectively. Compared with TAx TAVR, DAo TAVR had a lower Society of Thoracic Surgery (STS) score, shorter fluoroscopic time, and less contrast volume use. The 30-day mortality rates were significantly higher in the DAo TAVR group (9.6%, 95% confidence interval (CI) = [8.4–10.9]) than in the TAx TAVR group (5.7%, 95% CI = [4.8–6.8]; P for heterogeneity

Background Surgery for tricuspid valve (TV) diseases is associated with poor prognosis, but few studies have described the long‐term outcomes by comparing TV repair and replacement in isolated and concomitant TV surgeries separately. Methods and Results Between 2000 and 2013, adult patients who underwent TV repair or replacement surgeries were identified from the Taiwan National Health Insurance Research Database. Outcomes of interest included all‐cause mortality, composite outcome, and readmission attributable to any cause. Inverse probability of treatment weighting was used to reduce confounding effects. A total of 2644 patients with a mean follow‐up of 4.9 years were included. Of them, 12.6% and 87.4% underwent isolated and concomitant TV surgery, respectively. The in‐hospital mortality rates for isolated and concomitant TV surgery were 8.7% and 8.6%, respectively, whereas all‐cause mortality rates were 41.7% and 36.8%, respectively. Compared with TV replacement, TV repair demonstrated significantly lower risks of all‐cause mortality (concomitant: hazard ratio [HR], 0.76; 95% CI, 0.59–0.99), composite outcome (isolated: subdistribution HR, 0.55; 95% CI, 0.35–0.89; concomitant: subdistribution HR, 0.63; 95% CI, 0.46–0.86), and readmission (isolated: subdistribution HR, 0.64; 95% CI, 0.46–0.91; concomitant: subdistribution HR, 0.72; 95% CI, 0.60–0.86), except insignificant difference in all‐cause mortality in isolated surgery. Conclusions Compared with replacement, TV repair is associated with better short‐ and long‐term outcomes in both isolated and concomitant TV surgery. However, further prospective clinical trials are warranted.

BACKGROUND:Transcatheter aortic valve-in-valve (VIV) procedure is a safe alternative to conventional reoperation for bioprosthetic dysfunction. Balloon-expandable valve (BEV) and self-expanding valve (SEV) are the 2 major types of devices used. Evidence regarding the comparison of the 2 valves remains scarce. METHODS:A systematic review and meta-analysis was conducted to compare the outcomes of BEV and SEV in transcatheter VIV for aortic bioprostheses dysfunction. A computerized search of Medline, PubMed, Embase, and Cochrane databases was performed. English-language journal articles reporting SEV or BEV outcomes of at least 10 patients were included. RESULTS:In total, 27 studies were included, with 2,269 and 1,671 patients in the BEV and SEV groups, respectively. Rates of 30-day mortality and stroke did not differ significantly between the 2 groups. However, BEV was associated with significantly lower rates of postprocedural permanent pacemaker implantation (3.8% vs. 12%; P < 0.001). Regarding echocardiographic parameters, SEV was associated with larger postprocedural effective orifice area at 30 days (1.53 cm2 vs. 1.23 cm2; P < 0.001) and 1 year (1.55 cm2 vs. 1.22 cm2; P < 0.001). CONCLUSIONS:For patients who underwent transcatheter aortic VIV, SEV was associated with larger postprocedural effective orifice area but higher rates of permanent pacemaker implantation. These findings provide valuable information for optimizing device selection for transcatheter aortic VIV.

BackgroundLittle is known about the effects of anticoagulation in patients with atrial fibrillation (AF) and left atrial enlargement (LAE).MethodsData of patients with AF were retrieved from Chang Gung Research Database during 2007-2016. We excluded patients who were not using oral anticoagulants, used anticoagulants for ResultsWe identified 40,777 patients who received a diagnosis of AF. After the exclusion criteria were applied, 6,445 patients remained, 4,922 with LAE, and they were followed up for 2.4 ±1.9 years. The mean age of the patients was 77.32 ± 0.18 in the NOAC group and 76.58 ± 6.91 in the warfarin group (p < 0.0001); 48.24% of patients in the NOAC group and 46.98% of patients in the warfarin group were men (p > 0.05). The mean CHA2DS2-VASc score was 3.26 ± 1.05 in the NOAC group and 3.07 ± 1.12 in the warfarin group (p < 0.0001). The mean HAS-BLED score was 3.87 ± 3.81 in the NOAC group and 3.86 ± 3.80 in the warfarin group (p > 0.05). Furthermore, the mean LA diameter was 4.75 ± 0.63 cm in the warfarin group and 4.79 ± 0.69 cm in the warfarin group (p > 0.05). Among patients with LAE, NOAC was associated with significantly reduced IS/SE events (CRR = 0.63, 95% CI = 0.52-0.77), no difference in major bleeding (CRR = 0.91, 95% CI = 0.78-1.05), and significantly reduced death from any cause (aHR = 0.65, 95% CI = 0.52-0.80) compared with warfarin.ConclusionsIn elderly patients with AF and LAE, NOAC was associated with reduced IS/SE and death from any cause compared with warfarin, whereas no difference in major bleeding was observed between these treatments.

Background: The percentage of patients referred for coronary artery bypass grafting (CABG) who have previously undergone percutaneous coronary interventions (PCIs) is increasing. The purpose of this study was to review the outcomes of patients who had received coronary stenting before CABG, and to examine the validity of a mortality risk stratification system in this patient group. Methods: From 2010 to 2012, 439 patients who underwent isolated CABG at our medical center were reviewed. The patients were divided into two study groups: those who had previously received coronary artery stenting (97 patients, 24.7%), and those who had not (342 patients, 75.3%). The patients who received balloon angioplasty were excluded. Results: There were no significant differences in baseline characteristics. The prior stenting group had a lower risk of mortality, although the difference was not significant. The prior stenting group had fewer graft anastomoses (p = 0.005), and hence a significantly shorter cardiopulmonary bypass time (p = 0.045) and shorter aortic cross-clamping time. Surgical mortality was similar between the two groups. The durations of intensive care unit stay and hospitalization were also similar. The discriminatory power of the logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) was lower in both group. Conclusions: Prior coronary stenting does not affect short-term mortality in patients subsequently undergoing CABG surgery. The EuroSCORE does not predict perioperative mortality well for the patients who undergo coronary stenting before CABG.

It was highlighted that in the original article [1] the data on categorical variables was wrongly arranged in Table 1 and there was an incorrect statement in the fourth paragraph of the Discussion section.

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 (NOACs) 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 NOACs may be considered for such patients.

BackgroundPatients with cirrhosis and acute myocardial infarction (AMI) present dilemma whether dual antiplatelet therapy (DAPT) should be used.MethodsElectronic medical records between 2001-2013 were retrieved from Taiwan National Health Insurance Research Database. Patients were excluded for missing information, age ResultsA total of 150,887 patients with AMI retrieved. After exclusion criteria and propensity score-matching, 914 cirrhotic and 3,656 non-cirrhotic patients with AMI on DAPT were studied. During 1-year follow-up, there was significantly increased mortality in cirrhotic patients compared to non-cirrhotic patients (HR = 1.49, 95% CI = 1.28-1.74). There was significantly decreased recurrent MI in cirrhotic patients compared to non-cirrhotic patients (subdistribution HR [SHR] = 0.71, 95% CI = 0.54-0.92). However, non-significantly increased major bleeding (SHR = 1.23, 95% CI = 0.87-1.73) and significantly increased gastrointestinal bleeding (SHR = 1.49, 95% CI = 1.31-1.70).ConclusionsIn cirrhotic patients with AMI, DAPT offers benefit with decreased recurrent MI at the expense of increased gastrointestinal bleeding.

ObjectiveWhether the cardiovascular (CV) outcomes of second-generation limus-eluting stents (LESs) differ from those of paclitaxel-eluting stents (PESs) in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) is still unclear.MethodsWe used the Taiwan National Health Insurance Research Database to analyse data of 516 patients with AMI and CS diagnosed from January 2007 to December 2011. We used propensity score matching to adjust for the imbalance in covariate baseline values between these two groups. We evaluated clinical outcomes by comparing 197 subjects who used second-generation LESs to 319 matched subjects who used PESs.ResultsThe risk of the primary composite outcomes (i.e., myocardial infarction, coronary revascularisation or CV death) was significantly lower in the second-generation LES group than in the PES group [37.3% vs. 51.8%; hazard ratio (HR), 0.73; 95% CI: 0.56-0.95] at the 12-month follow-up. The patients who received second-generation LESs had a lower risk of coronary revascularisation (HR 0.62; 95% CI: 0.41-0.93) than those who used PESs. However, the risks of myocardial infarction (HR 0.56; 95% CI: 0.26-1.24), ischemic stroke (HR 0.73; 95% CI: 0.23-2.35), or CV death (HR 0.90; 95% CI: 0.63-1.28) were not significantly different between the two groups.ConclusionsAmong patients with CS-complicating AMI, second-generation LES implantation significantly reduced the risk of coronary revascularisation and composite CV events compared to PES implantation at the 12-month follow-up.

BackgroundAcute kidney injury (AKI) is a common complication of extracorporeal membrane oxygenation (ECMO) treatment. The aim of this study was to elucidate the long-term outcomes of adult patients with AKI who receive ECMO.Materials and methodsThe study analyzed encrypted datasets from Taiwan's National Health Insurance Research Database. The data of 3251 patients who received first-time ECMO treatment between January 1, 2003, and December 31, 2013, were analyzed. Characteristics and outcomes were compared between patients who required dialysis for AKI (D-AKI) and those who did not in order to evaluate the impact of D-AKI on long-term mortality and major adverse kidney events.ResultsOf the 3251 patients, 54.1% had D-AKI. Compared with the patients without D-AKI, those with D-AKI had higher rates of all-cause mortality (52.3% vs. 33.3%; adjusted hazard ratio [aHR] 1.82, 95% confidence interval [CI] 1.53-2.17), chronic kidney disease (13.7% vs. 8.1%; adjusted subdistribution HR [aSHR] 1.66, 95% CI 1.16-2.38), and end-stage renal disease (5.2% vs. 0.5%; aSHR 14.28, 95% CI 4.67-43.62). The long-term mortality of patients who survived more than 90 days after discharge was 22.0% (153/695), 32.3% (91/282), and 50.0% (10/20) in the patients without D-AKI, with recovery D-AKI, and with nonrecovery D-AKI who required long-term dialysis, respectively, demonstrating a significant trend (Pfor trend ConclusionAKI is associated with an increased risk of long-term mortality and major adverse kidney events in adult patients who receive ECMO.