Semaglutide modulates prothrombotic and atherosclerotic mechanisms, associated with epicardial fat, neutrophils and endothelial cells network.

BACKGROUND: Obesity has increased in recent years with consequences on diabetes and other comorbidities. Thus, 1 out of 3 diabetic patients suffers cardiovascular disease (CVD). The network among glucose, immune system, endothelium and epicardial fat has an important role on pro-inflammatory and thrombotic mechanisms of atherogenesis. Since semaglutide, long-acting glucagon like peptide 1- receptor agonist (GLP-1-RA), a glucose-lowering drug, reduces body weight, we aimed to study its effects on human epicardial fat (EAT), aortic endothelial cells and neutrophils as atherogenesis involved-cardiovascular cells. METHODS: EAT and subcutaneous fat (SAT) were collected from patients undergoing cardiac surgery. Differential glucose consumption and protein cargo of fat-released exosomes, after semaglutide or/and insulin treatment were analyzed by enzymatic and TripleTOF, respectively. Human neutrophils phenotype and their adhesion to aortic endothelial cells (HAEC) or angiogenesis were analyzed by flow cytometry and functional fluorescence analysis. Immune cells and plasma protein markers were determined by flow cytometry and Luminex-multiplex on patients before and after 6 months treatment with semaglutide. RESULTS: GLP-1 receptor was expressed on fat and neutrophils. Differential exosomes-protein cargo was identified on EAT explants after semaglutide treatment. This drug increased secretion of gelsolin, antithrombotic protein, by EAT, modulated CD11b on neutrophils, its migration and endothelial adhesion, induced by adiposity protein, FABP4, or a chemoattractant. Monocytes and neutrophils phenotype and plasma adiposity, stretch, mesothelial, fibrotic, and inflammatory markers on patients underwent semaglutide treatment for 6 months showed a 20% reduction with statistical significance on FABP4 levels and an 80% increase of neutrophils-CD88. CONCLUSION: Semaglutide increases endocrine activity of epicardial fat with antithrombotic properties. Moreover, this drug modulates the pro-inflammatory and atherogenic profile induced by the adiposity marker, FABP4, which is also reduced in patients after semaglutide treatment.

Enhancing patient outcomes: Integrating electronic cardiology consultation in primary care for cancer patients.

BACKGROUND: The prevalence of cancer patients with concomitant cardiovascular (CV) disease is on the rise due to improved cancer prognoses. The aim of this study is to evaluate the long-term outcomes of cancer patients referred to a cardiology department (CD) via primary care using e-consultation. METHODS: We analysed data from cancer patients with prior referrals to a CD between 2010 and 2021 (n = 6889) and compared two care models: traditional in-person consultations and e-consultations. In e-consultation model, cardiologists reviewed electronic health records (e-consultation) to determine whether the demand could be addressed remotely or necessitated an in-person consultation. We used an interrupted time series regression model to assess outcomes during the two periods: (1) time to cardiology consultation, (2) rates of all-cause and CV related hospital admissions and (3) rates of all-cause and CV-related mortality within the first year after the initial consultation or e-consultation at the CD. RESULTS: Introduction of e-consultation for cancer patients referred to cardiology care led to a 51.8% reduction (95%CI: 51.7%-51.9%) in waiting times. Furthermore, we observed decreased 1-year incidence rates, with incidence rate ratios (iRRs) [IC95%] of .75 [.73-.77] for CV-related hospitalizations, .43 [.42-.44] for all-cause hospitalizations, and .87 [.86-.88] for all-cause mortality. CONCLUSIONS: Compared to traditional in-person consultations, an outpatient care program incorporating e-consultation for cancer patients significantly reduced waiting times for cardiology care and demonstrated safety, associated with lower rates of hospital admissions.

The impact of inter-clinician electronic consultation in patients diagnosed with atrial fibrillation in primary care.

BACKGROUND: An early diagnosis and early initiation of oral anticoagulants (OAC) are main determinants for outcomes in patients with atrial fibrillation (AF). Inter-clinician electronic consultations (e-consultations) program for the general practitioner referrals to cardiologist may improve health care access by reducing the elapsed time for cardiology care. OBJECTIVE: To evaluate the effect of a reduced elapsed time to care after a inter-clinician e-consultations program implementation (2013-2019) in comparison with previous in-person consultation (2010-2012) in the outpatient health care management in a Cardiology Department. METHODOLOGY: We included 10,488 patients with AF from 1 January 2010, to 31 December 2019. Until 2012, all patients attended an in-person consultation (2010-2012). In 2013, we instituted an e-consult program (2013-2019) for all primary care referrals to cardiologists that preceded patient's in-person consultation when considered. The shared electronic patient dossier (EPD) was available between GP and cardiologist, and any change in therapy advice from cardiologist was directly implemented in this EPD. RESULTS: During the e-consultation period (2013-2019) were referred 6627 patients by GPs to cardiology versus 3861 during the in-person consultation (2010-2012). The e-consultation implementation was associated with a reduction in the elapsed time to anticoagulation prescription (177.6 ± 8.9 vs. 22.5 ± 8.1 days, p < .001), and an increase of OAC use (61% [95% IC: 19.6%-102.4%], p < .001). The e-consult program implementation was associated with a reduction in the 1-year CV mortality (.48 [95% CI: .30-.75]) and all-cause mortality (.42 [95% CI: .29-.62]). The OAC reduces the stroke mortality (.15 [95% CI: .06-.39]) and CV mortality (.43 [95% CI: .29-.62]) and all-cause mortality (.23 [95% CI: .17-.31]). CONCLUSION: A shared EPD-based inter-clinician e-consultation program significantly reduced the elapsed time for cardiology consultation and initiation of OAC. The implementation of this program was associated with a lower risk of stroke and cardiovascular/all-cause mortality.

Gender differences on healthcare accessibility and outcomes of a electronic inter-clinician consultation program at the cardiology department in a Galician Health Area.

AIMS: To assess the longer-term results (hospital admissions and mortality) in women versus men referred to a cardiology department from primary care using an e-consultation in our outpatient care programme. METHODS: We selected 61,306 patients (30,312 women and 30,994 men) who visited the cardiology service at least once between 2010 and 2021: 69.1% (19,997 women and 20,462 men) were attended in e-consultation (from 2013 to 2021) and 30.9% (8920 women and 9136 men) in in-person consultations (from 2010 to 2012) without gender differences in the proportion of patients attended in each period. Using an interrupted time series regression model, we analysed the impact of incorporating e-consultation into the healthcare model and evaluated the elapsed time to cardiology care, heart failure (HF), cardiovascular (CV), and all-cause hospital admissions and mortality during the one-year after cardiology consultation. RESULTS: The introduction of e-consultation substantially decreased waiting times to cardiology care; during the in-person consultation period, the mean delay for cardiology care was 57.9 (24.8) days in men and 55.8 (22.8) days in women. During the e-consultation period, the waiting time to cardiology care was markedly reduced to 9.41 (4.02) days in men and 9.46 (4.18) in women. After e-consultation implantation, there was a significant reduction in the 1-year rate of hospital admissions and mortality, both in women and men iRR [IC 95%]: 0.95 [0.93-0.96] for HF, 0.90 [0.89-0.91] for CV and 0.70 [0.69-0.71] for all-cause hospitalization; and 0.93 [0.92-0.95] for HF, 0.86 [0.86-0.87] for CV and 0.88 [0.87-0.89] for all-cause mortality in women; and 0.91 [0.89-0.92] for HF, 0.90 [0.89-0.91] for CV and 0.72 [0.71-0.73] for all-cause hospitalization; and 0.96 [0.93-0.97] for HF, 0.87 [95% CI: 0.86-0.87] for CV and 0.87 [0.86-0.87] for all-cause mortality, in men. CONCLUSION: Compared with the in-person consultation period, an outpatient care programme that includes an e-consultation significantly reduced waiting time to cardiology care and was safe, with a lower rate of hospital admissions and mortality in the first year, without significative gender differences.

Diabesity in Elderly Cardiovascular Disease Patients: Mechanisms and Regulators.

Cardiovascular disease (CVD) is the leading cause of death in the world. In 2019, 550 million people were suffering from CVD and 18 million of them died as a result. Most of them had associated risk factors such as high fasting glucose, which caused 134 million deaths, and obesity, which accounted for 5.02 million deaths. Diabesity, a combination of type 2 diabetes and obesity, contributes to cardiac, metabolic, inflammation and neurohumoral changes that determine cardiac dysfunction (diabesity-related cardiomyopathy). Epicardial adipose tissue (EAT) is distributed around the myocardium, promoting myocardial inflammation and fibrosis, and is associated with an increased risk of heart failure, particularly with preserved systolic function, atrial fibrillation and coronary atherosclerosis. In fact, several hypoglycaemic drugs have demonstrated a volume reduction of EAT and effects on its metabolic and inflammation profile. However, it is necessary to improve knowledge of the diabesity pathophysiologic mechanisms involved in the development and progression of cardiovascular diseases for comprehensive patient management including drugs to optimize glucometabolic control. This review presents the mechanisms of diabesity associated with cardiovascular disease and their therapeutic implications.

Combined Sodium-Glucose-Transporters Inhibitors and Glucagon-Like-Peptide Receptor Agonist Compared with Monotherapy Improves Long-Term Survival: A Real-World Registry.

BACKGROUND: The benefits of new glucose-lowering agents on cardiovascular disease have been demonstrated in randomized clinical trials. However, more evidence is required to assess the additive value of a combined therapy based on sodium-glucose transporter inhibitors (SGLT2i) and glucagon-like peptide receptor agonists (GLP1ra) in a real-world population. METHODS: A nonconcurrent prospective study was conducted using integrated electronic medical records from primary care and hospitals obtained through "big data" technologies in a healthy area in Galicia. The study involved patients who were given SGLT2i, GLP1ra, or both treatments between January 2018 and June 2022 and were categorized as either mono- or combined therapy (SGLT2i, GLP1ra, or both). The cumulative risk for different events: hospitalization or mortality, or both, for 1) coronary artery disease, 2) heart failure, 3) cerebrovascular accident, and all-cause mortality were represented by Kaplan-Meier curves and multivariate Cox regression analysis to obtain the hazard ratio (HR) and (95% confidence interval [CI]). Validation was performed in a subpopulation with propensity score matching. RESULTS: The patients (15,549) who were included were median (standard deviation) 68 (12) years old, with 41% of them being female and 46% experiencing obesity. The median (interquartile range) of follow-up was 19 (8-33) months. The Kaplan-Meier analysis determined that the cumulative risk for coronary artery disease and cerebrovascular accident events was similar among the 3 different therapy groups. However, the combined therapy vs SGLT2i reduced the risk of heart failure events (HR 0.69; 95% CI, 0.56-0.87) or all-cause mortality (HR 0.68; 95% CI, 0.54-0.86). Multivariate Cox regression analysis, after matching with a propensity score, confirmed the benefits of combined therapy regarding SGLT2i or GLP1ra monotherapy. CONCLUSION: Compared with SGLT2i or GLP1ra alone, combined therapy SGLT2i + GLP1ra reduces heart failure risk and all-cause mortality in a real-world population.

Impact of a clinician-to-clinician electronic consultation in heart failure patients with previous hospital admissions.

Aims: To evaluate the impact of an outpatient care management programme that includes a clinician-to-clinician e-consultation on delay time in care, hospital admissions, and mortality in a high-risk group of patients with heart failure (HF) and previous episodes of HF hospitalization (HFH). Methods and results: We selected 6444 HF patients who visited the cardiology service at least once between 2010 and 2021. Of these, 4851 were attended in e-consult, and 2230 had previous HFH. Using an interrupted time series regression model, we analysed the impact of incorporating e-consult into the healthcare model in the group of patients with HFH and evaluated the elapsed time to cardiology care, HF, cardiovascular (CV), and all-cause hospital admissions and mortality, calculating the incidence relative risk (iRR). In the group of patients with HFH, the introduction of e-consult substantially decreased waiting times to cardiology care (8.6 [8.7] vs. 55.4 [79.9] days, P < 0.001). In that group of patients, after e-consult implantation, hospital admissions for HF were reduced (iRR [95%CI]: 0.837 [0.840-0.833]), 0.900 [0.862-0.949] for CV and 0.699 [0.678-0.726] for all-cause hospitalizations. There was also lower mortality (iRR [95%CI]: 0.715 [0.657-0.798] due to HF, 0.737 [0.764-0.706] for CV and 0.687 [0.652-0.718] for all-cause). The improved outcomes after e-consultation implementation were significantly higher in the group of patients with previous HFH. Conclusion: In patients with HFH, an outpatient care programme that includes an e-consult significantly reduced waiting times to cardiology care and was safe, with a lower rate of hospital admissions and mortality in the first year.

A clinician-to-clinician universal electronic consultation programme at the cardiology department of a Galician healthcare area improves healthcare accessibility and outcomes in elderly patients.

Aims: We aimed to assess longer-term results (accessibility, hospital admissions, and mortality) in elderly patients referred to a cardiology department (CD) from primary care using e-consultation in outpatient care. Methods and results: We included 9963 patients >80 years from 1 January 2010 to 31 December 2019. Until 2012, all patients attended an in-person consultation (2010-2012). In 2013, we instituted an e-consult programme (2013-2019) for all primary care referrals to cardiologists that preceded a patient's in-person consultation when considered. We used an interrupted time series (ITS) regression approach to investigate the impact of e-consultation on (i) cardiovascular hospital admissions and mortality. We also analysed (ii) the total number and referral rate (population-adjusted referred rate) in both periods, and (iii) the accessibility was measured as the number of consultations and variation according to the distance from the municipality and reference hospital. During e-consultation, the demand for care increased (12.8 ± 4.3% vs. 25.5 ± 11.1% per 1000 inhabitants, P < 0.001) and referrals from different areas were equalized. After the implementation of e-consultation, we observed that the increase in hospital admissions and mortality were stabilized [incidence rate ratio (iRR): 1.351 (95% CI, 0.787, 2.317), P = 0.874] and [iRR: 1.925 (95% CI: 0.889, 4.168), P = 0.096], respectively. The geographic variabilities in hospital admissions and mortality seen during the in-person consultation were stabilized after e-consultation implementation. Conclusions: Implementation of a clinician-to-clinician e-consultation programme in outpatient care was associated with improved accessibility to cardiology healthcare in elderly patients. After e-consultations were implemented, hospital admissions and mortality were stabilized.

Effects of guideline-directed medical therapy in patients with left bundle branch block-induced cardiomyopathy.

INTRODUCTION AND OBJECTIVES: Left bundle branch block (LBBB)-induced cardiomyopathy occurs in patients with long-standing LBBB. These patients characteristically exhibit hyperresponsiveness to cardiac resynchronization therapies (CRT). However, there is scarce information on their response to medical treatment. The aim of this study was to assess the change in left ventricular ejection fraction (LVEF) after a 3-month period following titration of guideline-directed medical therapy for heart failure. METHODS: This retrospective analysis included all patients assessed in the heart failure unit of a Spanish University Hospital between 2020 and 2021, who presented with de novo ventricular dysfunction (LVEF <40%) and had a history of long-standing LBBB with no other possible causes of cardiomyopathy. RESULTS: A total of 1497 patients were analyzed, of which 21 were finally eligible. Mean time from first diagnosis of LBBB to first consultation was 4.05± 4.1 years. Mean LVEF from first consultation to end of titration improved from 29.5±5.7% to 32.7±8.6% (P = .172), but none had recovered ventricular function at the end of follow-up. New York Heart Association functional class improved from 1.91±0.46 to 1.81±0.53 (P=.542). After CRT device implantation in 8 patients, LVEF improved by 18.1±6.4% (P=.003). CONCLUSIONS: Guideline-directed medical therapy seems to be ineffective in improving LVEF and functional class in patients with de novo heart failure and LBBB-induced cardiomyopathy. Based on a positive response to CRT on LVEF improvement, early CRT implantation could be a reasonable strategy for these patients.

An electronic consultation program impacts on heart failure patients' prognosis: implications for heart failure care.

AIMS: e-consults are asynchronous, clinician-to-clinician exchanges that answer focused, non-urgent, patient-specific questions using the electronic medical record. We instituted an e-consultation programme (2013-2019) for all general practitioners (GPs) referrals to cardiologists that preceded patients' in-person consultations when considered. In our study, we aimed to analyse the clinical characteristics, 1 year prognosis and the prognostic determinants of patients with a previous diagnosis of HF referred for an e-consult, categorized by their previous HF-related hospitalization status (recent hospitalization, <1 year before; remote hospitalization, >1 year before or never been hospitalized because of HF), and to analyse the impact of reducing the time elapsed between e-consultation and response by the cardiologist in terms of prognosis. METHODS AND RESULTS: Epidemiological and clinical data were obtained from 4851 HF patients referred by GPs to the cardiology department for an e-consultation 2013 and 2020. The delay of time to e-consults were solved was 8.6 + 8.6 days with 84.3% solved in <14 days. For the 1 year prognosis evaluation after the e-consult were assessed the cardiovascular hospitalizations, HF-related hospitalizations, HF-related mortality, cardiovascular mortality, and all-cause mortality. Compared with the group without a previous hospitalization, patients with recent and remote HF hospitalization were at higher risk of a new HF-related hospitalization (OR: 19.41 [95% CI: 12.95-29.11]; OR: 8.44 [95% CI: 5.14-13.87], respectively), HF-related mortality (OR: 2.47 [95% CI: 1.43-4.27]; OR: 1.25 [95% CI: 0.51-3.06], respectively), as well as cardiovascular hospitalizations and mortality and all-cause mortality. Reduction in the time elapsed because e-consultation was solved was associated with lower risk of HF-related mortality (OR: 0.94 [95% CI: 0.89-0.99]), cardiovascular mortality (OR: 0.96 [95% CI: 0.93-0.98]), and all-cause mortality (OR: 0.98 [95% CI: 0.97-1.00]). CONCLUSIONS: A clinician-to-clinician e-consultation programme between GPs and cardiologists in patients with HF allows to solve the demand of care in around 25% e-consults without an in-person consultation; the patients with a previous history of HF-related hospitalization showed a worse 1 year outcome. A reduction in the time elapsed because e-consultation was solved was associated with a mortality reduction.