Empagliflozin attenuates doxorubicin-induced cardiotoxicity by inhibiting the JNK signaling pathway.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors, such as empagliflozin, are pivotal therapies for heart failure. However, the effect of empagliflozin on doxorubicin-related cardiac dysfunction remains unclear. METHODS: Human induced pluripotent stem cell- and embryonic stem cell-derived cardiomyocytes were used to investigate the direct effect of empagliflozin on human cardiomyocytes. Then, the c-Jun amino-terminal kinases (JNK) inhibitor SP600125 was administered to the doxorubicin cardiotoxicity model in vitro and in vivo to investigate the role of JNK in empagliflozin. RESULTS: In human stem cell-derived cardiomyocytes, pretreatment with empagliflozin attenuated doxorubicin-induced cleavage of caspase 3 and other apoptosis markers. Empagliflozin significantly attenuated doxorubicin-induced phosphorylation of JNK and p38. Inhibiting the phosphorylation of JNK (SP600125) or STAT3 attenuated doxorubicin-induced apoptosis, but inhibiting the phosphorylation of p38 did not. SP600125 inhibits the phosphorylation of STAT3 (S727), and a STAT3 (Y705) inhibitor also inhibits the phosphorylation of JNK. Empagliflozin and SP600125 attenuated doxorubicin-induced increases in reactive oxygen species (ROS) and decreases in oxidized nicotinamide adenine dinucleotide (NAD+). In animal studies, empagliflozin and SP600125 attenuated doxorubicin-induced cardiac dysfunction and fibrosis. CONCLUSIONS: Empagliflozin attenuated doxorubicin-induced apoptosis by inhibiting the phosphorylation of JNK and its downstream signaling pathways, including ROS and NAD+.

Incidence, Risk Factors, and Outcomes of Left Atrial Enlargement in Patients Requiring Right Ventricular Pacing: A Retrospective Study of 461 Cases from 2012 to 2020.

BACKGROUND Long-term right ventricular (RV) pacing has been linked to left atrial enlargement (LAE). The incidence and risk factors associated with significant LAE after RV pacing remain unknown. This retrospective study included 461 patients requiring RV pacing at 2 centers between 2012 and 2020 and aimed to evaluate the incidence, risk factors, outcomes, and complications of LAE. MATERIAL AND METHODS A total of 461 patients with normal-sized pre-implant left atrial dimension and dual-chamber pacing pacemaker implantation for complete atrioventricular block were enrolled. Patients were grouped based on a ≥20% increase from their baseline left atrial dimension by echocardiography, indicating significant LAE, and initial characteristics, echocardiographic data, and outcomes were compared. RESULTS During a mean 7.0±4.9 years follow-up period, 96 patients (20.8%) developed significant LAE, whereas 365 patients did not. In multivariate logistic regression analysis, smaller pre-implant left atrial dimension (OR, 0.776; 95% CI, 0.728-0.828; P<0.001), lower post-implant left ventricular ejection fraction (OR, 0.976; 95% CI, 0.957-0.995; P=0.014), post-implant development of moderate to severe mitral regurgitation (OR, 2.357; 95% CI, 1.172-4.740; P=0.016), and RV pacing duration ≥3.3 years (OR, 1.576; 95% CI, 1.039-2.646; P=0.045) were independent predictors of significant LAE after RV-dependent pacing. There was a significant difference in the incident stroke events between patients without and with significant LAE (9.9% vs 17.7%; log-rank P=0.047). CONCLUSIONS Long-term RV pacing was linked to significant LAE in 20.8% of patients with complete atrioventricular block, with those affected experiencing a higher stroke rate during follow-up.

Downregulation of SIRT1 and GADD45G genes and left atrial fibrosis induced by right ventricular dependent pacing in a complete atrioventricular block pig model.

The molecular and genetic mechanisms underlying left atrial (LA) enlargement and atrial fibrosis following right ventricular (RV) dependent pacing remain unclear. Our objective was to investigate genetic expressions in the LA of pigs subjected to RV pacing for atrioventricular block (AVB), as well as to identify the differential gene expressions affected by biventricular (BiV) pacing. We established an AVB pig model and divided the subjects into three groups: a sham control group, an RV pacing group, and a BiV pacing group. Differential expression genes (DEGs) analyses conducted through next-generation sequencing (NGS) and enrichment analyses were employed to identify genes with altered expression in the LA myocardium. The RV pacing group showed a significant increase in extracellular fibrosis in the LA myocardium compared to the control group. NGS analysis revealed suppressed expression of the sirtuin signaling pathway in the RV pacing group. Among the DEGs within this pathway, GADD45G was found to be downregulated in the RV pacing group and upregulated in the BiV pacing group. Remarkably, the BiV pacing group exhibited elevated levels of GADD45G protein. In our study, we observed significant downregulation of SIRT1 and GADD45G genes, which are associated with the sirtuin signaling pathway, in the LA myocardium of the RV pacing group when compared to the control group. Moreover, these genes, which were downregulated in the RV pacing group, displayed a noteworthy upregulation in the BiV pacing group when compared to the RV pacing group.

Taiwan Association for the Study of the Liver-Taiwan Society of Cardiology Taiwan position statement for the management of metabolic dysfunction- associated fatty liver disease and cardiovascular diseases.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is an increasingly common liver disease worldwide. MAFLD is diagnosed based on the presence of steatosis on images, histological findings, or serum marker levels as well as the presence of at least one of the three metabolic features: overweight/obesity, type 2 diabetes mellitus, and metabolic risk factors. MAFLD is not only a liver disease but also a factor contributing to or related to cardiovascular diseases (CVD), which is the major etiology responsible for morbidity and mortality in patients with MAFLD. Hence, understanding the association between MAFLD and CVD, surveillance and risk stratification of MAFLD in patients with CVD, and assessment of the current status of MAFLD management are urgent requirements for both hepatologists and cardiologists. This Taiwan position statement reviews the literature and provides suggestions regarding the epidemiology, etiology, risk factors, risk stratification, nonpharmacological interventions, and potential drug treatments of MAFLD, focusing on its association with CVD.

HLA-Ehigh /HLA-Ghigh /HLA-IIlow Human iPSC-Derived Cardiomyocytes Exhibit Low Immunogenicity for Heart Regeneration.

Although human pluripotent stem cells (hPSCs)-derived cardiomyocytes (hPSC-CMs) can remuscularize infarcted hearts and restore post-infarct cardiac function, post-transplant rejection resulting from human leukocyte antigen (HLA) mismatching is an enormous obstacle. It is crucial to identify hypoimmunogenic hPSCs for allogeneic cell therapy. This study is conducted to demonstrate the immune privilege of HLA-Ehigh /HLA-Ghigh /HLA-IIlow human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs). Ischemia-reperfusion surgery is done to create transmural myocardial infarction in rats. At post-infarct 4 days, hPSC-CMs (1.0×107 cells per kg), including human embryonic stem cell-derived cardiomyocytes (hESC-CMs), HLA-Elow/HLA-Glow/HLA-IIhigh hiPSC-CMs, and HLA-Ehigh /HLA-Ghigh /HLA-IIlow hiPSC-CMs, are injected into the infarcted myocardium. Under the treatment of very low dose cyclosporine A (CsA), only HLA-Ehigh /HLA-Ghigh /HLA-IIlow hiPSC-CMs survive in vivo and improved post-infarct cardiac function with infarct size reduction. HLA-Ehigh /HLA-Ghigh /HLA-IIlow hiPSC-CMs activate the SHP-1 signaling pathway of natural killer (NK) cells and cytotoxic T cells to evade attack by NK cells and cytotoxic T cells. Herein, it is demonstrated that using a clinically relevant CsA dose, HLA-Ehigh /HLA-Ghigh /HLA-IIlow hiPSC-CMs repair the infarcted myocardium and restore the post-infarct heart function. HLA-Ehigh /HLA-Ghigh /HLA-IIlow hiPSCs are less immunogenic and may serve as platforms for regeneration medicine.

Rationale and Study Design of the TSOC-Fully Organized Registry for the Management of Symptomatic ACS Study (T-FORMOSA Study).

Background: Successful implementation of practice guidelines has been challenging in the treatment of acute coronary syndrome (ACS), leaving room for improvement. A nationwide registry can provide more information than that recorded in the National Health Insurance Research Database (NHIRD). Methods: We conducted a prospective, nationwide, multi-center ACS full spectrum registry involving 3600 patients admitted to hospitals within 24 hours of the onset of myocardial infarction with ST-segment elevation or ACS without ST-segment elevation. In total, 41 sites including medical centers and regional hospitals were selected across Taiwan. The data for each patient are collected at 3 time points for the main study: during hospitalization, 6 months, and 12 months after the discharge. The milestone for first patient in was reached on January 7, 2022, and complete enrollment is expected before October 2023. The primary aims of the main study are to determine the degree of guideline-directed medical therapies and to identify prognostic predictors associated with 1-year composite outcomes, including death, myocardial infarction, stroke, and unplanned coronary revascularization in ACS patients. Thereafter, the patient data will be analyzed every 3 to 5 years for up to 20 years after discharge using the NHIRD in the extended study. Conclusions: We hypothesized that a greater increase in the implementation of guideline-directed medical therapies can be observed. The results of the current study will add new and important information regarding a broad spectrum of ACS to drive further investigations.

Application of genetic risk score for in-stent restenosis of second- and third-generation drug-eluting stents in geriatric patients.

BACKGROUND: The second-and third-generation drug-eluting stents (DESs) in-stent restenosis (ISR) genetic risk score (GRS) model has been previously validated. However, the model has not been validated in geriatric patients. Therefore, we conducted this study to test the feasibility of the DES-ISR GRS model in geriatric patients with coronary artery disease (CAD) in Taiwan. METHODS: We conducted a retrospective, single-center cohort study and included geriatric patients (age ≥ 65 years) with CAD and second-or third-generation DES(s) deployment. Patients undergoing maintenance dialysis were excluded. ISR was defined as ≥ 50% luminal narrowing on the follow-up coronary arteriography. The DES-ISR GRS model included five selected exonic single-nucleotide polymorphisms (SNPs): CAMLG, GALNT2, C11orf84, THOC5, and SAMD11. The GRS was defined as the sum of the five selected SNPs for the risk allele. RESULTS: We enrolled 298 geriatric patients from January 2010 and December 2019 in this study. After propensity score matching, there were 192 geriatric patients with CAD in the final analysis, of which 32 patients had ISR. Patients were divided into two groups based on their GRS values: low (0-2) and high (≥ 3) GRS. A high GRS was significantly associated with DES-ISR in geriatric patients. CONCLUSION: Those geriatric patients with a high GRS had significantly higher second-or third-generation DES ISR rates. The five SNP-derived DES-ISR GRS model could provide genetic information for interventional cardiologists to treat geriatric patients with CAD. TRIAL REGISTRATION: The primary study protocol was registered with clinicaltrials.org. with registration number: NCT03877614; on March 15, 2019. ( http://clinicaltrials.gov/ct2/show/NCT03877614 ).

Optical Nanobiosensor-Based Point-of-Care Testing for Cardiovascular Disease Biomarkers.

Cardiovascular disease is a global health threat, and detecting cardiac biomarkers is essential for early-stage diagnosis and personalized treatment. Traditional approaches have limitations, but optical nanobiosensors offer rapid, highly selective, and sensitive detection. Optical nanobiosensors generate biosignals that transfer light signals while analytes bind with the bioreceptors. Optical nanobiosensors have advantages such as ease of monitoring, low cost, a wide detection range, and high sensitivity without any interference. An optical nanobiosensor platform is a promising approach for point-of-care cardiac biomarker detection with a low detection limit. This review mainly focuses on the detection of cardiovascular disease biomarkers based on various optical nanobiosensor approaches that have been reported during the last five years, and we have categorized them based on optical signal readouts. A detailed discussion of the classification of cardiovascular disease biomarkers, design strategies of optical biosensors, types of optically active nanomaterials, types of bioreceptors, functionalization techniques, various assay types, and sensing mechanisms is presented. Then, we summarize the optical signaling readout-based various nanobiosensors systems for the detection of cardiovascular disease biomarkers. Finally, we summarize and conclude with the recent development of point-of-care testing (PoCT) for cardiovascular disease biomarkers used in various optical readout techniques.

2023 Consensus of Taiwan Society of Cardiology on the Pharmacological Treatment of Chronic Heart Failure.

The prevalence of heart failure is increasing, causing a tremendous burden on health care systems around the world. Although mortality rate of heart failure has been significantly reduced by several effective agents in the past 3 decades, yet it remains high in observational studies. More recently, several new classes of drugs emerged with significant efficacy in reducing mortality and hospitalization in chronic heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). To integrate these effective therapies and prioritize them in the management of Asian patients, Taiwan Society of Cardiology has recently appointed a working group to formulate a consensus of pharmacological treatment in patients with chronic heart failure. Based on most updated information, this consensus provides rationales for prioritization, rapid sequencing, and in-hospital initiation of both foundational and additional therapies for patients with chronic heart failure.

Renal denervation reverses ventricular structural and functional remodeling in failing rabbit hearts.

Renal denervation (RDN) suppresses the activity of the renin-angiotensin-aldosterone system and inflammatory cytokines, leading to the prevention of cardiac remodeling. Limited studies have reported the effects of renal denervation on ventricular electrophysiology. We aimed to use optical mapping to evaluate the effect of RDN on ventricular structural and electrical remodeling in a tachycardia-induced cardiomyopathy rabbit model. Eighteen rabbits were randomized into 4 groups: sham control group (n = 5), renal denervation group receiving RDN (n = 5), heart failure group receiving rapid ventricular pacing for 1 month (n = 4), and RDN-heart failure group (n = 4). Rabbit hearts were harvested for optical mapping. Different cycle lengths were paced (400, 300, 250, 200, and 150 ms), and the results were analyzed. In optical mapping, the heart failure group had a significantly slower epicardial ventricular conduction velocity than the other three groups. The RDN-heart failure, sham control, and RDN groups had similar velocities. We then analyzed the 80% action potential duration at different pacing cycle lengths, which showed a shorter action potential duration as cycle length decreased (P for trend < 0.01), which was consistent across all groups. The heart failure group had a significantly longer action potential duration than the sham control and RDN groups. Action potential duration was shorter in the RDN-heart failure group than the heart failure group (P < 0.05). Reduction of conduction velocity and prolongation of action potential duration are significant hallmarks of heart failure, and RDN reverses these remodeling processes.

The Effects of Post-Acute Care in Patients with Heart Failure in Taiwan: A Single Center Experience.

Background: The National Health Insurance Administration in Taiwan has promoted the heart failure post-acute care (HF-PAC) program as a means to provide proactive integrated care within the optimal treatment timeframe to enhance functional recovery after acute decompensated heart failure (HF). Objectives: The aim of this program was to reduce HF readmission rates, improved medication prescription rates, and improve the quality of life in HF patients. Methods: Patients who had a reduced left ventricular ejection fraction (LVEF) of ≤ 40% were included and followed up for 6 months after discharge. They underwent cardiac rehabilitation and physiological, and nutritional status evaluations. The main clinical outcomes of the HF-PAC program were guideline-directed medical therapy prescription rate and 6-month readmission rate. Results: A total of 122 patients were recruited from June 2018 to December 2020 at a medical center in southern Taiwan. The patients' activities of daily living, nutritional status, quality of life and LVEF were significantly improved during the HF-PAC program. More than 95% of the patients received guideline-directed medical prescriptions at the end of the HF-PAC program. The cardiovascular-related 6-month re-admission rate after the HF-PAC program ended was 27.7%, and it could be predicted by the New York Health Association functional class [hazard ratio (HR) 95% confidence interval (95% CI) = 4.12 (1.36-12.46)], value of the Mini Nutritional Assessment - Short Form [HR (95% CI) = 0.46 (0.31-0.68)] and LVEF [HR (95% CI) = 0.95 (0.91-0.99)]. Conclusions: By incorporating multidisciplinary healthcare teams, the HF-PAC program improves the guideline- directed medical therapy prescription rate, thus improving patients' cardiac function, physical activity recovery, the quality of life, and also reduces their readmission rate.

Management of Restenosis after Stenting in Left Main Coronary Artery Disease.

Background: The optimal alternative treatment strategy to coronary artery bypass graft surgery (CABG) for in-stent restenosis (ISR) in left main (LM) coronary artery disease remains uncertain. Methods: We retrospectively screened all intervention reports from an intervention database and extracted those mentioning an LM stent. We then manually confirmed reports involving LM ISR and divided them into two groups, those in which the patient received a new drug-eluting stent (new-DES) strategy, and those in which the patient received a drug-coated balloon (DCB) only. A composite endpoint of major adverse cardiovascular events (MACEs) and each individual endpoint were compared. We also performed a brief analysis of similar designed studies. Results: Between the new-DES (n = 40) and DCB-only (n = 22) groups, during median respective follow-up times of 581.5 and 642.5 days, no significant statistical differences were detected in MACEs (50.0% vs. 50.0%, p = 0.974), cardiovascular death (27.5% vs. 13.6%, p = 0.214), nonfatal myocardial infarction (30.0% vs. 31.8%, p = 0.835), or target lesion revascularization (35.0% vs. 45.5%, p = 0.542). We analyzed four similar studies and found comparable MACE findings (odds ratio: 0.85, 95% CI: 0.44-1.67). Conclusions: Our findings support both DCB angioplasty and repeat DES implantation for LMISR lesions in patients who were clinically judged to be unsuitable for CABG; the treatments achieved comparable clinical results in terms of MACEs in the medium term.

Interplay between fish oil, obesity and cardiometabolic diabetes.

Diabetes, dyslipidemia, obesity, and cardiac dysfunction are the hallmarks of the cardiometabolic syndrome. Pathogens include hypercoagulability, inflammation, endothelial dysfunction, and oxidative stress. Increased white fat, nonalcoholic fatty liver disease, diabetes, and cardiovascular disease are caused by obesity. Depression increases the risk of future obesity, a surprising link between obesity and neuropathology. High glucose levels, abnormal lipids, and metabolic syndrome are the root causes of CVD associated with diabetes. Diets high in fat induce insulin resistance and liver fat. Inflammation, diminished insulin signaling, and ectopic lipid accumulation are the causes of ectopic lipid accumulation. Polyunsaturated fatty acids with eicosapentaenoic acid and docohexasonoic acid inhibit the synthesis of triglycerides and increase their clearance. Omega-3 regulates the nervous system, blood pressure, hematic clotting, glucose tolerance, and inflammation. However, anxiety and depression can cause cardiovascular disease. It has been shown that PUFAs found in fish oil can improve glucose and lipid metabolism, cardiac membrane composition, and inflammation in the body. By repairing the dysregulation of metabolic syndrome, fish oil is a potential therapeutic target for cardiovascular diseases.

High Burden of Premature Ventricular Complex Increases the Risk of New-Onset Atrial Fibrillation.

Background High burden of premature ventricular complex (PVC) leads to increased cardiovascular mortality. A recent nationwide population-based study demonstrated that PVC is associated with an increased risk of atrial fibrillation (AF). However, the relationship between PVC burden and new-onset AF has not been investigated. The purpose of the study is to elucidate whether PVC burden is associated with new-onset AF. Methods and Results We designed a single-center, retrospective, large population-based cohort study to evaluate the role of PVC burden and new-onset AF in Taiwan. Patients who were AF naïve with PVC were divided into the low burden group (<1000/day) and moderate-to-high burden group (≥1000/day) based on the 24-h Holter ECG report. New-onset AF was defined as a new or first detectable event of either a persistent or paroxysmal AF. A total of 16 030 patients who were AF naïve and underwent 24-h Holter ECG monitoring were enrolled in this study, with a mean follow-up time of 973 days. A propensity score-matched analysis demonstrated that the moderate-to-high burden PVC group had a higher risk of developing new-onset AF than that of the low burden PVC group (4.91% versus 2.73%, P<0.001). Multivariate Cox regression analysis showed that moderate-to-high burden of PVC is an independent risk factor for new-onset AF. The Kaplan-Meier analysis demonstrated that patients with moderate-to-high PVC burden were associated with higher risk of new-onset AF (log-rank P<0.001). Conclusions PVC burden is associated with new-onset AF. Patients with moderate-to-high PVC burden are at a higher risk of new-onset AF. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03877614.

Manual compression technique improves the success rate in the treatment of thrombosed aneurysmal arteriovenous fistula: A single-center experience.

OBJECTIVE: Endovascular intervention for thrombosed aneurysmal arteriovenous fistula (AVF) is still a challenge. Manual compression technique (MCT)-assisted angioplasty may be helpful, but there is no evidence or data to support it. METHODS: From January 2018 to May 2021, patients with thrombosed aneurysmal AVFs were retrospectively enrolled. The patients were separated into the MCT group or the traditional group according to the procedure received. Technical failure, clinical failure, 90-day patency, and safety were analyzed. RESULTS: A total of 159 cases (64 ± 12 years old, 60% male) were enrolled, of which 87 cases received MCT and 72 underwent traditional angioplasty. No technical failure was observed in the MCT group, while five technical failures were observed in the traditional group (0% vs. 7%, p = 0.02). There were no differences in the clinical failure rate (3% vs. 7%, p = 0.30), 90-day patency rate, or procedure time between the MCT group and the traditional group. There was no symptomatic pulmonary embolism or other complication in the two groups. CONCLUSION: MCT is a low-cost, less invasive, and safe procedure for thrombosed aneurysmal AVF, and it achieves a higher technical success rate than traditional angioplasty.

Pentraxin 3 regulates tyrosine kinase inhibitor-associated cardiomyocyte contraction and mitochondrial dysfunction via ERK/JNK signalling pathways.

BACKGROUND: Hepatocellular carcinoma (HCC) patients suffer varying degrees of heart dysfunction after tyrosine kinase inhibitor (TKI) treatment. Interestingly, HCC patients often have higher levels of pentraxin 3 (PTX3), and PTX3 inhibition was found to improve left ventricular dysfunction in animal models. OBJECTIVES: We sought to assess the therapeutic potential of PTX3 inhibition on TKI-associated cardiotoxicity. METHODS: We used a human embryonic stem cell line, RUES2, to generate cardiomyocyte cultures (RUES2-CM) for functional testing. We also assessed heart function and PTX3 expression levels in 16 HCC patients who received TKI treatment, 3 HCC patients who did not receive TKIs, and 7 healthy volunteers. RESULTS: Significantly higher PTX3 expression was noted in HCC patients with TKI treatment versus those without, and 38% of male and 33% of female patients had QTc prolongation after TKI treatment. Treatment of cardiomyocyte cultures with sorafenib also increased PTX3 expression and induced cytoskeletal remodelling, contraction reduction, sodium current inhibition, and mitochondrial respiratory dysfunction. PTX3 colocalised with CD44 in cardiomyocytes, and cardiomyocyte contraction, mitochondrial respiratory function, and regular cytoskeletal and apoptotic protein expression were restored with PTX3 inhibition. CD44 knockdown confirmed PTX3/CD44 signalling. These results suggest a possible mechanism in which sorafenib treatment increases PTX3 expression, thereby resulting in reduced extracellular signal-regulated kinase (ERK) 1/2 expression that affects cardiomyocyte contraction, while also activating c-Jun N-terminal kinase (JNK) downstream pathways to disrupt mitochondrial respiration and trigger apoptosis. CONCLUSIONS: TKI-induced cardiotoxicity may be partly mediated by the upregulation of PTX3, and thus PTX3 inhibition has potential as a therapeutic strategy.

Evolutionary changes in thrombus features on computed tomography: An effective approach for identifying subacute pulmonary embolism.

OBJECTIVE: Thrombus features on computed tomography (CT) play a key role in distinguishing between acute and chronic pulmonary embolisms (PEs). However, the thrombus features of subacute PE are largely unknown. METHODS: This retrospective study included 358 patients (age, 65 ± 16 years; percentage of men, 38%) diagnosed with PE from 2008 to 2019. The patients were divided into a study group and a verification group. Thrombus features that changed over time were determined in the study group according to the time of PE occurrence. Next, we determined the thrombus features of subacute PE and verified them in the verification group. Finally, we compared clinical deterioration and the 1-month mortality rate between the patients with acute and subacute PEs. RESULTS: The main feature of eccentric thrombi that changed over time was the angle with the arterial wall, whereas those of centric thrombi were recanalization and heterogeneity. Taken together, the features of subacute PE were determined to be an obtuse angle with the arterial wall, recanalization, and heterogeneity. The accuracy of these features in identifying subacute PE was 94% during verification. Between the patients with acute and subacute PEs, there was no significant difference in clinical deterioration (19% vs 14%; P = .32) or the 1-month mortality rate (15% vs 8%; P = .11). With multivariate analysis, subacute events were also not associated with clinical deterioration (P = .8) or the 1-month mortality rate (P = .11). CONCLUSIONS: We determined the time trend of thrombus features on CT in patients with PE and found that these features can improve the identification of subacute events. Patients with acute and subacute PEs do not have different risks of clinical deterioration and 1-month mortality.

Underestimating the Risk of an Inconclusive Result in Exercise Treadmill Tests for Patients With Suspected Ischemic Heart Disease.

BACKGROUND: The exercise stress test is a widely used noninvasive test for diagnosing ischemic heart disease. Patients with a "positive" result have a higher risk than those with a "negative" result. However, the outcomes of patients with an "inconclusive" result remain uncertain.Methods and Results: We retrospectively collected the data of patients who underwent an ECG-based treadmill stress test between August 2009 and March 2020. Propensity score matching (PSM) was performed to adjust for confounders. Clinical outcomes were compared in terms of all-cause death and cardiovascular (CV) death. Subgroup analysis evaluated treatment interactions, including medication and examinations. In total, 25,475 patients were recruited, and after exclusion and PSM, 4,847 (1,621 with a positive result, 1,606 with a negative result, and 1,621 with an inconclusive result) remained. Compared with the negative group, the inconclusive group, but not the positive group, had a significantly worse outcome in terms of all-cause death (hazard ratio [HR]: 1.834, 95% confidence interval [CI]: 1.34-2.511 and HR: 1.327, 95% CI: 0.949-1.857, respectively); however, CV death was not significantly different in the inconclusive and positive groups (HR: 1.728, 95% CI: 0.413-7.232 and HR: 2.067, 95% CI: 0.517-8.264, respectively). CONCLUSIONS: Clinicians must not underestimate the potential for worse outcomes in patients with an inconclusive stress test result.