Drug-Eluting Resorbable Scaffold versus Angioplasty for Infrapopliteal Artery Disease.

BACKGROUND: Among patients with chronic limb-threatening ischemia (CLTI) and infrapopliteal artery disease, angioplasty has been associated with frequent reintervention and adverse limb outcomes from restenosis. The effect of the use of drug-eluting resorbable scaffolds on these outcomes remains unknown. METHODS: In this multicenter, randomized, controlled trial, 261 patients with CLTI and infrapopliteal artery disease were randomly assigned in a 2:1 ratio to receive treatment with an everolimus-eluting resorbable scaffold or angioplasty. The primary efficacy end point was freedom from the following events at 1 year: amputation above the ankle of the target limb, occlusion of the target vessel, clinically driven revascularization of the target lesion, and binary restenosis of the target lesion. The primary safety end point was freedom from major adverse limb events at 6 months and from perioperative death. RESULTS: The primary efficacy end point was observed (i.e., no events occurred) in 135 of 173 patients in the scaffold group and 48 of 88 patients in the angioplasty group (Kaplan-Meier estimate, 74% vs. 44%; absolute difference, 30 percentage points; 95% confidence interval [CI], 15 to 46; one-sided P<0.001 for superiority). The primary safety end point was observed in 165 of 170 patients in the scaffold group and 90 of 90 patients in the angioplasty group (absolute difference, -3 percentage points; 95% CI, -6 to 0; one-sided P<0.001 for noninferiority). Serious adverse events related to the index procedure occurred in 2% of the patients in the scaffold group and 3% of those in the angioplasty group. CONCLUSIONS: Among patients with CLTI due to infrapopliteal artery disease, the use of an everolimus-eluting resorbable scaffold was superior to angioplasty with respect to the primary efficacy end point. (Funded by Abbott; LIFE-BTK ClinicalTrials.gov number, NCT04227899.).

Dual Antithrombotic Therapy versus Anticoagulant Monotherapy for Major Adverse Limb Events in Patients with Concomitant Lower Extremity Arterial Disease and Atrial Fibrillation: A Propensity Score Weighted Analysis.

OBJECTIVE: Patients with symptomatic lower extremity arterial disease (LEAD) are recommended to receive antiplatelet therapy, while direct oral anticoagulants (DOACs) are standard for stroke prevention in patients with atrial fibrillation (AF). For patients with concomitant LEAD and AF, data comparing dual antithrombotic therapy (an antiplatelet agent used in conjunction with a DOAC) vs. DOAC monotherapy are scarce. This retrospective cohort study, based on data from the Taiwan National Health Insurance Research Database, aimed to compare the efficacy and safety of these antithrombotic strategies. METHODS: Patients with AF who underwent revascularisation for LEAD between 2012 - 2020 and received any DOAC within 30 days of discharge were included. Patients were grouped by antiplatelet agent exposure into the dual antithrombotic therapy and DOAC monotherapy groups. Inverse probability of treatment weighting was used to mitigate selection bias. Major adverse limb events (MALEs), ischaemic stroke or systemic embolism, and bleeding outcomes were compared. Patients were followed until the occurrence of any study outcome, death, or up to two years. RESULTS: A total of 1 470 patients were identified, with 736 in the dual antithrombotic therapy group and 734 in the DOAC monotherapy group. Among them, 1 346 patients received endovascular therapy as the index revascularisation procedure and 124 underwent bypass surgery. At two years, dual antithrombotic therapy was associated with a higher risk of MALEs than DOAC monotherapy (subdistribution hazard ratio [SHR] 1.34, 95% confidence interval [CI] 1.15 - 1.56), primarily driven by increased repeat revascularisation. Dual antithrombotic therapy was also associated with a higher risk of major bleeding (SHR 1.43, 95% CI 1.05 - 1.94) and gastrointestinal bleeding (SHR 2.17, 95% CI 1.42 - 3.33) than DOAC monotherapy. CONCLUSION: In patients with concomitant LEAD and AF who underwent peripheral revascularisation, DOAC monotherapy was associated with a lower risk of MALEs and bleeding events than dual antithrombotic therapy.

Costs and Cardiovascular Benefits of a Fourth-Generation Synchronous Telehealth Program on Mortality and Cardiovascular Outcomes for Patients With Atrial Fibrillation: Retrospective Cohort Study.

BACKGROUND: The prevalence of atrial fibrillation (AF) continues to increase in modern aging society. Patients with AF are at high risk for multiple adverse cardiovascular events, including heart failure, stroke, and mortality. Improved medical care is needed for patients with AF to enhance their quality of life and limit their medical resource utilization. With advances in the internet and technology, telehealth programs are now widely used in medical care. A fourth-generation telehealth program offers synchronous and continuous medical attention in response to physiological parameters measured at home. Although we have previously shown the benefits of this telehealth program for some patients with a high risk of cardiovascular disease, its benefits for patients with AF remains uncertain. OBJECTIVE: This study aims to investigate the benefits of participating in a fourth-generation telehealth program for patients with AF in relation to cardiovascular outcomes. METHODS: This was a retrospective cohort study. We retrospectively searched the medical records database of a tertiary medical center in Northern Taiwan between January 2007 and December 2017. We screened 5062 patients with cardiovascular disease and enrolled 537 patients with AF, of which 279 participated in the telehealth program and 258 did not. Bias was reduced using the inverse probability of treatment weighting adjustment based on the propensity score. Outcomes were collected and analyzed, including all-cause readmission, admission for heart failure, acute coronary syndrome, ischemic stroke, systemic embolism, bleeding events, all-cause mortality, and cardiovascular death within the follow-up period. Total medical expenses and medical costs in different departments were also compared. Subgroup analyses were conducted on ischemic stroke stratified by several subgroup variables. RESULTS: The mean follow-up period was 3.0 (SD 1.7) years for the telehealth group and 3.4 (SD 1.9) years for the control group. After inverse probability of treatment weighting adjustment, the patients in the telehealth program had significantly fewer ischemic strokes (2.0 vs 4.5 events per 100 person-years; subdistribution hazard ratio [SHR] 0.45, 95% CI 0.22-0.92) and cardiovascular deaths (2.5 vs 5.9 events per 100 person-years; SHR 0.43, 95% CI 0.18-0.99) at the follow-up. The telehealth program particularly benefited patients comorbid with vascular disease (SHR 0.11, 95% CI 0.02-0.53 vs SHR 1.16, 95% CI 0.44-3.09; P=.01 for interaction). The total medical expenses during follow-up were similar in the telehealth and control groups. CONCLUSIONS: This study demonstrated the benefits of participating in the fourth-generation telehealth program for patients with AF by significantly reducing their ischemic stroke risk while spending the same amount on medical expenses.

Does the diagnostic timing of cancer-associated thromboembolism influence the survival outcome in ovarian cancer patients?

BACKGROUND/PURPOSE: Efforts were made to explore the influence of diagnostic timing for cancer-associated thromboembolic events on survival of ovarian cancer patients. METHODS: We reviewed the medical records of 75 ovarian cancer patients with thromboembolism and evaluated the prognostic factors affecting disease-free survival and overall survival. RESULTS: These 75 patients were classified into two categories by the diagnostic timing of the thromboembolism, during (33 cases) and after (42 cases) initial diagnosis of ovarian cancer groups. The diagnostic timing of thromboembolism was not related to disease-free survival or overall survival of the studied population. Advanced disease stage, clear cell histology, interval debulking surgery, no recurrence/persistence of ovarian cancer, and patients treated with anticoagulant(s) treatment >3 months were associated with the disease-free survival. Advanced disease stage, clear cell histology, body mass index (BMI) ≥24 kg/m2 at the diagnosis of ovarian cancer, and no recurrence/persistence of ovarian cancer influenced the overall survival. In the subgroup analysis, compared to the after initial ovarian cancer diagnosis group, patients with stage I/II disease, BMI <24 kg/m2 at the diagnosis of ovarian cancer, or primary debulking surgery in the during cancer diagnosis group had longer disease-free survival, and overall survival benefit was observed in cases with stage I/II disease, or primary debulking surgery. CONCLUSION: The diagnostic timing of thromboembolism was not related to disease-free or overall survival of ovarian cancer patients, but associated with that of specific patient subgroups.

2024 TSOC/TSPS Joint Consensus: Strategies for Advanced Vascular Wound Management in Arterial and Venous Diseases.

The Taiwan Society of Cardiology (TSOC) and Taiwan Society of Plastic Surgery (TSPS) have collaborated to develop a joint consensus for the management of patients with advanced vascular wounds. The taskforce comprises experts including preventive cardiologists, interventionists, and cardiovascular and plastic surgeons. The consensus focuses on addressing the challenges in diagnosing, treating, and managing complex wounds; incorporates the perfusion evaluation and the advanced vascular wound care team; and highlights the importance of cross-disciplinary teamwork. The aim of this joint consensus is to manage patients with advanced vascular wounds and encourage the adoption of these guidelines by healthcare professionals to improve patient care and outcomes. The guidelines encompass a range of topics, including the definition of advanced vascular wounds, increased awareness, team structure, epidemiology, clinical presentation, medical treatment, endovascular intervention, vascular surgery, infection control, advanced wound management, and evaluation of treatment results. It also outlines a detailed protocol for assessing patients with lower leg wounds, provides guidance on consultation and referral processes, and offers recommendations for various wound care devices, dressings, and products. The 2024 TSOC/TSPS consensus for the management of patients with advanced vascular wounds serves as a catalyst for international collaboration, promoting knowledge exchange and facilitating advancements in the field of advanced vascular wound management. By providing a comprehensive and evidence-based approach, this consensus aims to contribute to improved patient care and outcomes globally.

Prediabetes increases the risk of major limb and cardiovascular events.

BACKGROUND: Prediabetes, an intermediate stage between normal blood sugar levels and a diabetes mellitus diagnosis, is increasing in prevalence. Severe prediabetes is associated with a similar risk of complications as diabetes, but its relationship with peripheral arterial disease remains underexplored. METHODS: We conducted a retrospective cohort study involving 36,950 adult patients, utilizing electronic medical records from the National Taiwan University Hospital between 2014 and 2019. We employed multivariable Cox regression and Kaplan-Meier analysis with the log-rank test to analyze major adverse limb events (MALE) and major adverse cardiovascular events (MACE) in relation to normal glucose regulation (NGR) and prediabetes. RESULTS: During the 131,783 person-years follow-up, 17,754 cases of prediabetes and 19,196 individuals with normal glucose regulation (NGR) were identified. Kaplan-Meier analysis revealed an increased incidence of both MALE and MACE in individuals with prediabetes. (log-rank p = 0.024 and < 0.001). Prediabetes exhibited a significant association with an elevated risk of MALE (adjusted hazard ratio (aHR) 1.26 [95% CI 1.10-1.46], p = 0.001) and MACE (aHR 1.46 [1.27-1.67], p < 0.001). Furthermore, in individuals with prediabetes, the elevation in the risk of MALE commenced before HbA1c levels surpassed 5.0% (for HbA1c 5.0-5.5%: aHR 1.78 (1.04-3.04), p = 0.036; HbA1c 5.5-6.0%: aHR 1.29 [1.06-1.58], p = 0.012; aHbA1c 6.0-6.5%: aHR 1.39 [1.14-1.70], p < 0.001). Similarly, the onset of increased MACE risk was observed when HbA1c levels exceeded 5.5% (for HbA1c 5.5-6.0%: aHR 1.67 [1.39-2.01], p < 0.001; HbA1c 6.0-6.5%: HR 2.10 [1.76-2.51], p < 0.001). Factors associated with both MALE and MACE in prediabetes include advanced age, male gender, higher body mass index, and a history of heart failure or atrial fibrillation. CONCLUSION: We demonstrated higher susceptibility to MALE and MACE in prediabetes compared to normoglycemic counterparts, notwithstanding lower HbA1c levels. Complications may manifest at an earlier prediabetes trajectory. Intensive lifestyle modification may improve the prognosis of severe prediabetes.

Correction: Effect of Telehealth Services on Mitral and Tricuspid Regurgitation Progression: Retrospective Study.

[This corrects the article DOI: 10.2196/47947.].

Effect of Telehealth Services on Mitral and Tricuspid Regurgitation Progression: Retrospective Study.

BACKGROUND: Mitral regurgitation (MR) and tricuspid regurgitation (TR) are common cardiac conditions with high mortality risks, which can be improved through early intervention. Telehealth services, which allow for remote monitoring of patient conditions, have been proven to improve the health management of chronic diseases, but the effects on MR and TR progression are unknown. OBJECTIVE: This study aimed to explore whether patients receiving telehealth services have less MR and TR progression compared with a control group. We also aimed to identify the determinants of MR and TR progression. METHODS: This single-center retrospective study conducted at the National Taiwan University Hospital compared MR and TR progression (defined as either progression to moderate or greater MR and TR or MR and TR progression by ≥2 grades during the study period) between the telehealth and control groups. Patients had a minimum of 2 transthoracic echocardiograms at least 6 months apart; baseline mild-moderate MR and TR or lower; and no prior surgeries on the mitral or tricuspid valve. Telehealth patients were defined as those who received telehealth services for at least 28 days within 3 months of baseline. Basic demographics, baseline blood pressure measurements, prescribed medication, and Charlson Comorbidity Index components were obtained for all patients. RESULTS: A total of 1081 patients (n=226 in the telehealth group and n=855 in the control group) were included in the study analyses. The telehealth group showed significantly lower baseline systolic blood pressure (P<.001), higher Charlson Comorbidity Index (P=.02), higher prevalence of prior myocardial infarction (P=.01) and heart failure (P<.001), higher beta-blocker (P=.03) and diuretic (P=.04) use, and lower nitrate use (P=.04). Both groups showed similar cardiac remodeling conditions at baseline. Telehealth was found to be neutral for both MR (hazard ratio 1.10, 95% CI 0.80-1.52; P=.52) and TR (hazard ratio 1.27, 95% CI 0.92-1.74; P=.14) progression. Determinants for moderate or greater MR progression included older age, female sex, diuretic use, larger left atrial dimension, left ventricular end-diastolic dimension, left ventricular end-systolic dimension, and lower left ventricular ejection fraction. Determinants of moderate or greater TR progression included older age, female sex, diuretic use, presence of atrial fibrillation, LA dimension, left ventricular end-systolic dimension, and lower left ventricular ejection fraction; statin use was found to be protective. CONCLUSIONS: This is the first study to assess the association between telehealth services and the progression of MR and TR. Telehealth patients, who had more comorbidities, displayed similar MR and TR progression versus control patients, indicating that telehealth may slow MR and TR progression. Determinants of MR and TR progression included easy-to-measure traditional echo parameters of cardiac function, older age, female sex, and atrial fibrillation, which can be incorporated into a telehealth platform and advanced alert system, improving patient outcomes through personalized care.

Cancer-Associated Thrombosis: A Taiwanese Perspective on Therapeutic Options with Focus on Non-Vitamin K Antagonist Oral Anticoagulants.

Cancer-associated thrombosis (CAT) is a common complication of malignancies. Patients with CAT are at risk of venous thromboembolism recurrence, but also at risk of bleeding while anticoagulated. Taiwanese patients are perceived to have a lower incidence of CAT, likely leading to false reassurance for Taiwanese patients with cancer. Because of this, oncologists and cardiologists from multiple medical institutions in Taiwan have set forth to provide clinical consensus guidelines on the management of CAT, based on local clinical practices and guided by predominant international clinical practice guidelines. This paper aims to describe the current disease burden of cancer-associated venous thromboembolism in Taiwanese cancer patients, and discusses the unmet needs and gaps in the management of this medical complication. It also outlines diagnostic and management strategies relevant to the different treatment options available, such as non-vitamin K antagonist oral anticoagulants.

Referral, Diagnosis, and Pharmacological Management of Peripheral Artery Disease: Perspectives from Taiwan.

Peripheral artery disease (PAD) imposes a heavy burden of major adverse cardiovascular events that are associated with considerable mortality and morbidity, and major adverse limb events (e.g., thrombectomy, revascularization, amputation) that can substantially impact patients' daily functioning and quality of life. Global registry data have indicated that PAD is an underdiagnosed disease in Taiwan, and its associated risk factors remain inadequately controlled. This review discusses the burden of PAD in Taiwan, major guidelines on PAD management, and the latest clinical trial outcomes. Practical experience, opinions, and the latest trial data were integrated to derive a series of clinical algorithms - patient referral, PAD diagnosis, and the antithrombotic management of PAD. These algorithms can be adapted not only by physicians in Taiwan involved in the clinical management of patients with PAD but also by general practitioners in local clinics and regional hospital settings, with the ultimate aim of improving the totality of PAD patient care in Taiwan.

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.

Major adverse cardiovascular and limb events in people with diabetes treated with GLP-1 receptor agonists vs SGLT2 inhibitors.

AIMS/HYPOTHESIS: This study aimed to assess the real-world outcomes of people with diabetes mellitus treated with glucagon-like peptide-1 receptor agonists (GLP1RAs) compared with those treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) in terms of major adverse cardiovascular and limb events. Peripheral artery disease is a common cause of morbidity in people with diabetes. Previous cardiovascular outcome trials have demonstrated the benefits of GLP1RAs and SGLT2is for reducing various cardiovascular events, but the safety and efficacy of these drugs on limb outcomes remain subject to debate and ambiguity. METHODS: A retrospective cohort study was conducted in which data were collected from the Taiwan National Health Insurance Research Database. In total, 379,256 individuals with diabetes receiving either GLP1RA or SGLT2i with treatment initiated between 1 May 2016 and 31 December 2019 were identified. The primary outcome was major adverse limb events (MALE), defined as the composite of newly diagnosed critical limb ischaemia, percutaneous transluminal angioplasty or peripheral bypass for peripheral artery disease, and non-traumatic amputation. The secondary outcome was major adverse cardiac events, which was a composite of cardiovascular death, non-fatal myocardial infarction and non-fatal ischaemic stroke. Other examined outcomes included death from any cause and hospitalisation for heart failure. Propensity score matching was performed at a 1:4 ratio between the GLP1RA and SGLT2i groups to mitigate possible selection bias. RESULTS: A total of 287,091 patients were eligible for analysis, with 81,152 patients treated with SGLT2i and 20,288 patients treated with GLP1RA after matching. The incidence of MALE was significantly lower in the GLP1RA group than in the SGLT2i group (3.6 vs 4.5 events per 1000 person-years; subdistribution HR 0.80; 95% CI 0.67, 0.96), primarily due to a lower incidence of critical limb ischaemia. The reduced risks of MALE associated with GLP1RA use were particularly noticeable in people with diabetic peripheral neuropathy (subdistribution HR 0.66 vs 1.11; p for interaction 0.006). CONCLUSIONS/INTERPRETATION: In people with diabetes, GLP1RA use was associated with significantly reduced risks of MALE compared with SGLT2i within the first 2 years after initiation, especially among people with diabetic neuropathy.

Mortality risk in patients with underweight or obesity with peripheral artery disease: a meta-analysis including 5,735,578 individuals.

OBJECTIVES: The "obesity paradox" - in which patients with obesity exhibit superior survival than normal-weight counterparts - has been reported for several diseases. However, obesity is a well-known risk factor for cardiovascular disease, and whether the obesity paradox is present in peripheral artery disease (PAD) is unknown. METHODS: A comprehensive search for studies that reported mortality in patients with PAD grouped by BMI identified 12 studies. We compared the survival of underweight patients with those who were not underweight, and patients with obesity against those without. Underweight was defined by a BMI value of <18.5 kg/m2 in most studies and obesity by BMI ≥ 30 kg/m2. Subgroup analyses were performed according to length of follow-up, presentation of PAD, and mode of revascularization. Meta-regression analyses were conducted, with covariates including age, sex, presence of coronary artery disease (CAD) and diabetes mellitus (DM). RESULTS: The mortality risk of underweight patients with PAD was significantly higher compared to those who are not underweight (HR 1.72, 95% CI 1.38-2.14; I2 = 84.2%). In contrast, the mortality risk of patients with obesity with PAD was significantly lower than those without (HR 0.78, 95% CI 0.62-0.97; I2 = 89.8%). These findings remained consistent regardless of the presentation of PAD, revascularization, age, sex, or presence of CAD. The risk of death in the short-term of underweight patients (HR 1.50, 95% CI 0.47-4.72) and patients with obesity (HR 0.86, 95% CI 0.66-1.13) were not significantly different from their counterparts. The meta-regression showed that of the association between obesity and better survival was more pronounced in studies with a greater proportion of patients with concomitant CAD (regression coefficient -0.029, 95% CI -0.054 to -0.004). CONCLUSIONS: In patients with PAD, mortality is higher among underweight patients and lower among patients with obesity. The mechanisms underlying the obesity paradox in patients with PAD remain to be elucidated, and further evidence is required to guide optimal weight control strategies in these patients.

Short- and Long-Term Outcomes of Catheter-Directed Thrombolysis versus Pulmonary Artery Embolectomy in Pulmonary Embolism: A National Population-Based Study.

OBJECTIVES: This study aimed to compare the short-term and long-term follow-up outcomes of catheter-directed thrombolysis (CDT) with those of pulmonary artery embolectomy (PAE) for patients with acute pulmonary embolism (PE) included in a nationwide cohort. BACKGROUND: Data allowing direct comparisons between CDT and PAE are lacking in the literature, and the optimal management of high-risk and intermediate-risk PE is still debated. METHODS: A retrospective cohort study was conducted with data for 2001 through 2013 collected from the Taiwan National Health Insurance Research Database (NHIRD). Patients who were first admitted for PE and treated with either CDT or PAE were included and compared. In-hospital outcomes included in-hospital death and safety (bleeding and cardiac arrhythmias) outcomes. Follow-up outcomes included all-cause mortality and recurrent PE during the 1- and 2-year follow-up periods and through the last follow-up. Inverse probability of treatment weighting (IPTW) based on the propensity score was used to minimize possible selection bias, including indices for multimorbidity such as the Charlson's Comorbidity Index (CCI) and HAS-BLED scores. RESULTS: A total of 389 patients treated between January 1, 2001, and December 31, 2013, were identified; 169 underwent CDT and 220 underwent PAE. After IPTW, there were no significant differences in in-hospital mortality (18.2% vs 21.3%; odds ratio 1.07, 95% confidence interval [CI]: 0.70-1.62) or the incidence of safety outcomes between the CDT and PAE groups. The risks of all-cause mortality (30% vs 29.5%; hazard ratio 1.16, 95% CI: 0.89-1.53), recurrent PE (7.2% vs 8.7%; subdistribution hazard ratio [SHR] 0.68, 95% CI: 0.39-1.21) and new-onset pulmonary hypertension (SHR 0.25, 95% CI: 0.05-1.32) were also not significantly different between the CDT and PAE groups at 2 years of follow-up. Subgroup analysis indicated that PAE may be associated with a more favorable 2-year mortality in patients <65 years old, patients with CCI scores of <3, patients with HAS-BLED scores of 1 to 2, and patients without cardiogenic shock (all P for interaction <.05). CONCLUSIONS: In patients with PE who required reperfusion therapy, CDT and PAE resulted in similar in-hospital and long-term all-cause mortality rates and long-term rates of recurrent PE. Bleeding risks were also comparable in the 2 groups.

A Dose Response Association Between Body Mass Index and Mortality in Patients with Peripheral Artery Disease: A Meta-analysis Including 5 729 272 Individuals.

OBJECTIVE: Obesity is a significant risk factor for atherosclerotic cardiovascular disease; however, the "obesity paradox", in which obese patients enjoy superior survival, has been observed in various cardiovascular conditions. Whether this phenomenon exists for peripheral artery disease (PAD) remains uncertain. The goal of this study was to evaluate the relationship between body mass index (BMI) and mortality in patients with PAD. METHODS: A comprehensive literature search identified seven eligible cohort studies that reported the association between BMI and all cause mortality in patients with PAD. A dose response meta-analysis was done for all cause mortality, short term (30 day or in hospital) mortality and long term mortality. The dose response association between BMI and mortality was also assessed in patients who received endovascular therapy (EVT). RESULTS: The non-linear dose response analysis showed that higher BMI values were associated with a lower mortality risk from the range between 15 kg/m2 to approximately 33 - 34 kg/m2. The risk of mortality increased slightly thereafter. This relationship was consistent with that of long term mortality but was not apparent in short term mortality. A U shaped relationship was also observed between BMI and mortality in patients who received EVT with the lowest mortality observed at around 30 kg/m2. CONCLUSION: The obesity paradox was evident in the analysis of long term survival among patients with PAD, with the lowest mortality rates observed in obese patients. However, this association was not observed for short term or in hospital mortality.

The Impact of Synchronous Telehealth Services With a Digital Platform on Day-by-Day Home Blood Pressure Variability in Patients with Cardiovascular Diseases: Retrospective Cohort Study.

BACKGROUND: Hypertension is associated with a large global disease burden with variable control rates across different regions and races. Telehealth has recently emerged as a health care strategy for managing chronic diseases, but there are few reports regarding the effects of synchronous telehealth services on home blood pressure (BP) control and variability. OBJECTIVE: The objective of this study is to investigate the effect of synchronous telehealth services with a digital platform on home BP. METHODS: This retrospective study was conducted by the Taiwan ELEctroHEALTH study group at the Telehealth Center of the National Taiwan University Hospital. We analyzed home BP data taken from 2888 patients with cardiovascular disease (CVD) enrolled in our telehealth program between 2009 to 2017. Of the 2888 patients with CVD, 348 (12.05%) patients who received home BP surveillance for ≥56 days were selected for BP analysis. Patients were stratified into three groups: (1) poorly controlled hypertension, (2) well-controlled hypertension, and (3) nonhypertension. The mean, SD, coefficient of variation (CV), and average real variability were calculated. RESULTS: Telehealth interventions significantly and steadily reduced systolic blood pressure (SBP) in the poorly controlled hypertension group from 144.8.2±9.2 to 133.7±10.2 mmHg after 2 months (P<.001). BP variability reduced in all patients: SBP-SD decreased from 7.8±3.4 to 7.3±3.4 after 2 months (P=.004), and SBP-CV decreased from 6.3±2.5 to 5.9±2.6 after 2 months (P=.004). Event-free survival (admission) analysis stratified by SBP-SD showed longer time to first hospitalization for Q1 patients compared with Q4 patients (P=.02, odds ratio 2.15, 95% CI 1.18-3.89). CONCLUSIONS: Synchronous telehealth intervention may improve home BP control and decrease day-by-day home BP variability in patients with CVD.

The efficacy and safety of novel classes of glucose-lowering drugs for cardiovascular outcomes: a network meta-analysis of randomised clinical trials.

AIMS/HYPOTHESIS: Several cardiovascular outcome trials on sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been released recently, including trials enrolling patients with congestive heart failure (CHF) and chronic kidney disease (CKD). Comparisons of the efficacy and safety of SGLT2i, glucagon-like peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i) thus require an update. Assessments in patient subgroups, i.e., as stratified by age or the presence of CHF, CKD or atherosclerotic cardiovascular disease (ASCVD), are also currently lacking. METHODS: We searched the PubMed, Embase and Cochrane databases for relevant studies published up until 5 December 2020. RCTs comparing SGLT2i, GLP-1RA and DPP-4i with placebo (or other controls) or with each other with cardiovascular (CV) or renal outcomes were eligible for inclusion. The primary efficacy endpoint was 3-point major adverse cardiovascular events (3P-MACE), which are defined as CV death, non-fatal myocardial infarction and non-fatal ischaemic stroke. All-cause mortality, hospitalisation for heart failure (HHF) and composite renal outcomes were also analysed. Pre-specified subgroup analyses of 3P-MACE were also performed. RESULTS: A total of 21 trials with 170,930 participants were included in this network meta-analysis. Both GLP-1RA and SGLT2i were associated with lower risks of 3P-MACE than placebo (RR 0.89, 95% CI 0.84, 0.94 and RR 0.88, 95% CI 0.83, 0.94, respectively). GLP-1RA and SGLT2i were also associated with lower risks of 3P-MACE than DPP-4i (RR 0.89, 95% CI 0.82, 0.98 and RR 0.89, 95% CI 0.81, 0.97, respectively). A comparison between SGLT2i and GLP-1RA demonstrated no difference in their risks of 3P-MACE (RR 0.99, 95% CI 0.91, 1.08). Only GLP-1RA was associated with a lower risk of stroke compared with placebo (RR 0.85, 95% CI 0.76, 0.94). SGLT2i is superior to GLP-1RA in reducing HHF (RR 0.76, 95% CI 0.68, 0.84) and renal outcomes (RR 0.78, 95% CI 0.65, 0.93). Subgroup analyses indicated that the benefits of SGLT2i and GLP-1RA were more pronounced in elderly patients, white and Asian patients, those with established ASCVD and those with longer durations of diabetes mellitus and worse glycaemic control. CONCLUSIONS/INTERPRETATION: SGLT2i and GLP-1RA are superior to DPP-4i in terms of CV and renal outcomes. GLP-1RA is the only drug class that reduces the risk of stroke. SGLT2i is superior in reducing HHF and renal outcomes. Therefore, the choice between SGLT2i and GLP-1RA should be individualised according to patient profiles. PROSPERO REGISTRATION NUMBER: CRD42020206600.

Major adverse cardiovascular and limb events in patients with diabetes treated with GLP-1 receptor agonists vs DPP-4 inhibitors.

AIMS/HYPOTHESIS: The safety and efficacy of glucagon-like peptide-1 receptor agonists (GLP1RAs) and dipeptidyl peptidase-4 inhibitors (DPP4is) in major cardiovascular adverse events were previously examined in cardiovascular outcome trials. However, the effects of these drugs on adverse limb outcomes were poorly examined. This study aimed to determine the real-world outcomes of patients with diabetes mellitus receiving GLP1RAs as compared with those receiving DPP4is in terms of major adverse cardiovascular and limb events. METHODS: A retrospective cohort study was conducted with data collected by the Taiwan National Health Insurance database between 1 May 2011 and 31 December 2017. Patients who were treated for type 2 diabetes with a GLP1RA or DDP4i during this period (n = 1,080,993), were identified. The primary outcome was a composite of major adverse limb events, defined as peripheral artery disease (PAD), critical limb ischaemia, percutaneous transluminal angioplasty or peripheral bypass for PAD, and amputation. The secondary cardiovascular outcome was the composite of cardiovascular death, non-fatal myocardial infarction and non-fatal ischaemic stroke. Propensity-score matching (PSM) at a 1:3 ratio between GLP1RA and DPP4i groups was done to minimise possible selection bias. RESULTS: A total of 948,342 individuals treated between 1 May 2011 and 31 December 2017, were identified, with 4460 in the GLP1RA group and 13,380 in the DPP4i group after PSM. The incidence of primary composite outcome events was significantly lower in those treated with GLP1RAs compared with those treated with DPP4is (2.59 vs 4.22 events per 1000 person-years; subdistribution HR [SHR] 0.63 [95% CI 0.41, 0.96]), primarily due to lower rates of amputation (1.29 events per 1000 person-years for GLP1RAs vs 2.4 events per 1000 person-years for DPP4is; SHR 0.55 [95% CI 0.30, 0.99]). Treatment with GLP1RAs was also associated with significantly lower risks of secondary composite outcome events (11.02 vs 17.95 events per 1000 person-years; HR 0.62 [95% CI 0.51, 0.76]). Moreover, the observed beneficial effects of GLP1RAs on reducing composite adverse limb outcomes were particularly noticeable in the non-cardiovascular patients and statin users (p for interaction <0.05). CONCLUSIONS/INTERPRETATION: In individuals with diabetes, the use of GLP1RAs was associated with significantly lower risks of major adverse limb events when compared with the use of DPP4is. The reduction in risk was driven largely by reduced rate of amputations. Moreover, treatment with GLP1RAs was also associated with lower risks of cardiovascular death, non-fatal stroke, non-fatal myocardial infarction and death from any cause. However, some unexplored confounding factors may exist in this observation study and future large-scale randomised controlled trials are needed.

The "rail sign": an ultrasound finding in placenta accreta spectrum indicating deep villous invasion and adverse outcomes.

BACKGROUND: Ultrasound has demonstrated a high accuracy in the prenatal diagnosis of placenta accreta spectrum. However, it is not known whether ultrasound findings can pinpoint the depths of villous invasion, recommend surgical strategies, and predict clinical outcomes. OBJECTIVE: We described an ultrasound descriptor for the placenta accreta spectrum and investigated whether it can predict the severity of villous invasion and clinical outcomes. STUDY DESIGN: The patients with placenta accreta spectrum in this retrospective cross-sectional study were diagnosed and managed in our hospital from 2002 to 2017. The placenta, with overlying myometrium and bladder, was mapped with color Doppler sonography while the patient's bladder was full. A "rail sign" was defined as 2 parallel neovascularizations depicted by color Doppler sonography over the uterovesical junction and bladder mucosa, with interconnecting bridging vessels perpendicular to both. The patients received serial ultrasound examinations and surgery at our hospital. An unpaired t test and Pearson chi-square test compared the pathology subtypes, surgical strategies, and clinical outcomes in patients with or without a rail sign. RESULTS: We enrolled 133 consecutive cases of placenta accreta spectrum confirmed either by surgical inspection or pathology examination. Patients with a rail sign had a significantly higher risk of an abnormally invasive placenta (placenta increta or placenta percreta) than those patients without a rail sign (83.3% [60 of 72] vs 27.9% [17 of 61]; odds ratio, 12.94; P<.001). In addition, patients with a rail sign had a higher probability of perioperative approaches, including preoperative vascular control (58.3% [42 of 72] vs 21.3% [13 of 61]; odds ratio, 5.17; P<.001) and uterine artery embolization (34.7% [25 of 72] vs 11.5% [7 of 61]; odds ratio, 4.1; P=.0002]. Furthermore, patients with a rail sign carried a higher risk of adverse clinical outcomes than patients without a rail sign, such as blood transfusion (80.6% [58 of 72] vs 36.1% [22 of 61]; odds ratio, 7.34; P<.001], admission to the intensive care unit (33.3% [24 of 72] vs 16.4% [10 of 61]; odds ratio, 2.55; P=.026), hysterectomy (75% [54 of 72] vs 24.6% [15 of 61]; odds ratio, 9.2; P<.001), and bladder invasion (16.7% [12 of 72] vs 4.9% [3 of 61]; odds ratio, 3.86; P=.033). Notably, the negative predictive value of bladder invasion was 95.1%, indicating a high confidence to reject bladder invasion while the rail sign was negative. When the rail sign was used as a screening test, the positive likelihood ratio of predicting deep villous invasion was 3.64 and correlated with an increased probability of 20% to 25%. Patients with a rail sign also had a greater blood loss (2944±2748 mL vs 1530±1895 mL; P<.001) and a longer hospital stay (11.9±10.9 days vs 8.6±7.1 days; P=.036) than patients without a rail sign. CONCLUSION: A "rail sign" depicted by color Doppler sonography correlates with deeper villous invasion, additional perioperative approaches, and more adverse outcomes.

The Costs and Cardiovascular Benefits in Patients With Peripheral Artery Disease From a Fourth-Generation Synchronous Telehealth Program: Retrospective Cohort Study.

BACKGROUND: Patients with peripheral artery disease (PAD) are at high risk for major cardiovascular events, including myocardial infarction, stroke, and hospitalization for heart failure. We have previously shown the clinical efficacy of a fourth-generation synchronous telehealth program for some patients, but the costs and cardiovascular benefits of the program for PAD patients remain unknown. OBJECTIVE: The telehealth program is now widely used by higher-risk cardiovascular patients to prevent further cardiovascular events. This study investigated whether patients with PAD would also have better cardiovascular outcomes after participating in the fourth-generation synchronous telehealth program. METHODS: This was a retrospective cohort study. We screened 5062 patients with cardiovascular diseases who were treated at National Taiwan University Hospital and then enrolled 391 patients with a diagnosis of PAD. Of these patients, 162 took part in the telehealth program, while 229 did not and thus served as control patients. Inverse probability of treatment weighting (IPTW) based on the propensity score was used to mitigate possible selection bias. Follow-up outcomes included heart failure hospitalization, acute coronary syndrome, stroke, and all-cause readmission during the 1-year follow-up period and through the last follow-up. RESULTS: The mean follow-up duration was 3.1 (SD 1.8) years for the patients who participated in the telehealth program and 3.2 (SD 1.8) for the control group. The telehealth program patients exhibited lower risk of ischemic stroke than did the control group in the first year after IPTW (0.9% vs 3.5%; hazard ratio [HR] 0.24; 95% CI 0.07-0.80). The 1-year composite endpoint of vascular accident, including acute coronary syndrome and stroke, was also significantly lower in the telehealth program group after IPTW (2.4% vs 5.2%; HR 0.46; 95% CI 0.21-0.997). At the end of the follow-up, the telehealth program group continued to exhibit a significantly lower rate of ischemic stroke than did the control group after IPTW (0.9% vs 3.5%; HR 0.52, 95% CI 0.28-0.93). Furthermore, the medical costs of the telehealth program patients were not higher than those of the control group, whether in terms of outpatient, emergency department, hospitalization, or total costs. CONCLUSIONS: The PAD patients who participated in the fourth-generation synchronous telehealth program exhibited lower risk of ischemic stroke events over both mid- and long-term follow-up periods. However, larger-scale and prospective randomized clinical trials are needed to confirm our findings.