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Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to improve cardiovascular outcomes not only in patients with diabetes but also in those with heart failure, irrespective of diabetic status. However, the mechanisms underlying the cardioprotective effects of these newer anti-diabetic drugs remain to be fully elucidated. One exciting avenue that has been recently explored in both preclinical and clinical studies is the modulation of the cardiovascular autonomic nervous system. A reduction in sympathetic nervous system activity by SGLT2 inhibitors may potentially translate into a reduction in arrhythmic risk and sudden arrhythmic death, which may explain, at least partly, the cardioprotection shown in the cardiovascular outcome trials with different SGLT2 inhibitors. Although some of the data from the preclinical and clinical studies are promising, overall the findings can be contradictory. This highlights the need for more studies to address gaps in our knowledge of these novel drugs. The present review offers an in depth overview of the existing literature regarding the role of SGLT2 inhibitors in modulating cardiovascular autonomic function as one of the possible pathways of their cardioprotective effects.
Assuntos
Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Diabetes Mellitus Tipo 2/metabolismo , Glucose/farmacologia , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Sódio/metabolismo , Transportador 2 de Glucose-Sódio/metabolismo , Transportador 2 de Glucose-Sódio/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Sistema Nervoso SimpáticoRESUMO
INTRODUCTION: Obstructive sleep apnoea (OSA) is associated with increased cardiovascular mortality despite continuous positive airways pressure (CPAP) therapy. This excess risk may be related to increased arrhythmia risk, especially atrial fibrillation (AF). The true incidence of arrhythmia in patients with OSA is unknown. Implantable loop recorders (ILR) are powerful tools for detecting arrhythmias long-term. Cardiac autonomic function may be important in arrhythmogenesis in these patients but needs further study. We aim to identify the true incidence of arrhythmias (especially AF) using ILRs, assess cardiac autonomic function using Holter monitors in patients with OSA and explore cardiovascular outcomes. METHODS AND ANALYSIS: A two-centre (University Hospital Coventry and St. Cross Hospital, Rugby) nested cohort study using Reveal LINQ (Medtronic, UK) ILR to identify precise arrhythmia (atrial/ventricular) incidence in patients with moderate-severe OSA. 200 patients will be randomised 1:1 to standard care alone or standard care+ILR (+Holter monitor at baseline and 12 months). The primary objective is to compare arrhythmia detection over 3 years between the two groups. Cardiac autonomic function will be assessed in the ILR-arm at baseline and 12 months post CPAP. Secondary objectives will explore the mechanisms linking OSA and arrhythmia using cardiac autonomic function parameters based on Holter recordings and circulating biomarkers (high sensitivity Troponin-T, N-terminal pro B-type natriuretic peptide, matrix metalloproteinase-9, fibroblast growth factor 23, high sensitivity C-reactive protein, interleukin-6 and tumour necrosis factor-α) before and after CPAP initiation in the ILR-arm. ETHICS AND DISSEMINATION: This study has been approved by the Health Research Authority after examination by the Solihull Research and Ethics Committee. The main ethical considerations was the minimally invasive nature of ILR insertion outside of usual care. Patient advisory groups were consulted with a positive outcome for this type of research. We plan on publishing papers in peer-reviewed journals based on the primary objective and any interesting findings from secondary objectives. We will endeavour to publish all relevant data. TRIAL REGISTRATION NUMBER: NCT03866148.
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Fibrilação Atrial , Apneia Obstrutiva do Sono , Humanos , Eletrocardiografia Ambulatorial , Estudos de Coortes , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Eletrocardiografia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/terapia , Pressão Positiva Contínua nas Vias Aéreas/métodosRESUMO
BACKGROUND: Implantable loop recorders (ILRs) are effective in achieving symptom-rhythm correlation. Data on the diagnostic yield of ILRs, on nurse-led syncope clinics, and on nurse-led ILR implants are limited. OBJECTIVE: We evaluated the safety and efficacy of our nurse-led syncope clinic and nurse-led ILR implants. METHODS: A retrospective study of all consecutive patients undergoing nurse-led ILR implantations was performed between April 2016 and April 2018. Patients were referred from both nurse-led and physician-led clinics. Data were collected on baseline demographic characteristics, referral source, symptom-rhythm correlation, ILR findings, and subsequent changes to management. All ILRs were enrolled into remote monitoring with automatic arrhythmia detection, and all immediate (≤24 hours) ILR implant complications were recorded. Comparisons were made between nurse-led and physician-led clinics and subsequent outcomes. RESULTS: A total of 432 patients with an ILR were identified: 164 (38%) from nurse-led and 268 (62%) from physician-led clinics; 200 (46%) were women (mean age 66.5 ± 18.2 years; mean follow-up duration 28.9 ± 9.5 months). Primary ILR indications were syncope (n = 251 [58%]), presyncope (n = 33 [7%]), palpitation (n = 39 [9%]), cryptogenic stroke (n = 78 [18%]), and other reasons (n = 31 [7%]). No immediate ILR implant complications occurred. Overall, 156 patients (36%) had a change in management as a direct result of ILR findings, with no overall differences between nurse-led and physician-led clinics (35% vs 36%; P = .7). More patients had newly diagnosed atrial fibrillation in physician-led clinics (15% vs 7%; P = .01), and more patients had pacemaker implants for bradycardia in nurse-led clinics (23% vs 13%; P < .01). CONCLUSION: Nurse-led ILR implantation was safe and effective. Nurse-led syncope clinics achieved good symptom-rhythm correlation with resultant significant changes to management in comparison to physician-led clinics. Larger prospective studies are needed to evaluate their longer-term impact.
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Fibrilação Atrial , Marca-Passo Artificial , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Eletrocardiografia Ambulatorial/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Papel do Profissional de Enfermagem , Marca-Passo Artificial/efeitos adversos , Estudos Retrospectivos , Síncope/diagnóstico , Síncope/etiologia , Síncope/terapiaRESUMO
BACKGROUND: Transvenous lead extraction (TLE) for implantable cardiac-devices is traditionally performed under general anesthesia (GA). This can lead to greater risk of exposure to COVID-19, longer recovery-times and increased procedural-costs. We report the feasibility/safety of TLE using conscious-sedation alone with immediate GA/cardiac-surgery back-up if needed. METHODS: Retrospective case-series of consecutive TLEs performed using conscious-sedation alone between March 2016 and December 2019. All were performed in the electrophysiology-laboratory using intravenous Fentanyl, Midazolam/Diazepam with a stepwise approach using locking-stylets/cutting-sheaths, including mechanical-sheaths. Baseline patient-characteristics, procedural-details and TLE outcomes (including procedure-related complications/death) were recorded. RESULTS: A total of 130 leads were targeted in 54 patients, mean age ± SD 74.6 ± 11.8years, 47(87%) males; dual-chamber pacemakers (n = 26; 48%), cardiac resynchronization therapy-defibrillators (n = 17; 31%) and defibrillators (n = 8; 15%) were commonest extracted devices. Mean ± SD/median (range) lead-dwell times were 11.0 ± 8.8/8.3 (0.3-37) years, respectively. Extraction indications included systemic infection (n = 23; 43%) and lead/pulse-generator erosion (n = 27; 50%); mean 2.1 ± 2.0 leads were removed per procedure/mean procedure-time was 100 ± 54 min. Local anesthetic (LA) was used for all (mean-dose: 33 ± 8 ml 1% lidocaine), IV drug-doses used (mean ± SD) were: midazolam: 3.95 ± 2.44 mg, diazepam: 4.69 ± 0.89 mg and fentanyl: 57 ± 40 µg. Complete lead-extraction was achieved in 110 (85%) leads, partial lead-extraction (<4 cm-fragment remaining) in 5 (4%) leads. Sedation-related hypotension requiring IV fluids occurred in 2 (managed without adverse-consequences) and hypoxia requiring additional airway-management in none. No procedural deaths occurred, one patient required emergency cardiac surgery for localized ventricular perforation, nine had minor complications (transient hypotension/bradycardia/pericardial effusion not requiring intervention). CONCLUSION: TLE undertaken using LA/conscious-sedation was safe/feasible in our series and associated with good clinical outcome/low procedural complications. Reduced risk of aerosolization of COVID-19 and quicker patient recovery/reduced anesthetic risk are potential benefits that warrant further study.
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BACKGROUND: Catheter ablation for complex left-atrial arrhythmia is increasing worldwide with many centres admitting patients overnight. Same-day procedures using conscious sedation carry significant benefits to patients/healthcare providers but data are limited. We evaluated the safety and cost-effectiveness of same-day complex left-atrial arrhythmia ablation. METHOD: Multi-centre retrospective cohort study of all consecutive complex elective left-atrial ablation procedures performed between January 2011 and December 2019. Data were collected on planned same-day discharge versus overnight stay, baseline parameters, procedure details/success, ablation technology, post-operative complications, unplanned overnight admissions/outcomes at 4-months and mortality up to April 2020. A cost analysis of potential savings was also performed. RESULTS: A total of 967 consecutive patients underwent complex left-ablation using radiofrequency (point-by-point ablation aided by 3D-mapping or PVAC catheter ablation with fluoroscopic screening) or cryoballoon-ablation (mean age: 60.9 ± 11.6 years, range 23-83 yrs., 572 [59%] females). The majority of patients had isolation of pulmonary veins alone (n = 846, 87%) and most using conscious-sedation alone (n = 921, 95%). Of the total cohort, 414 (43%) had planned same-day procedure with 35 (8%) admitted overnight due to major (n = 5) or minor (n = 30) complications. Overall acute procedural success-rate was 96% (n = 932). Complications in planned overnight-stay/same-day cohorts were low. At 4-month follow-up there were 62 (6.4%) readmissions (femoral haematomas, palpitation, other reasons); there were 3 deaths at mean follow-up of 42.0 ± 27.6 months, none related to the procedure. Overnight stay costs £350; the same-day ablation policy over this period would have saved £310,450. CONCLUSIONS: Same-day complex left-atrial catheter ablation using conscious sedation is safe and cost-effective with significant benefits for patients and healthcare providers. This is especially important in the current financial climate and Covid-19 pandemic.
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Procedimentos Cirúrgicos Ambulatórios/economia , Arritmias Cardíacas/cirurgia , Ablação por Cateter/economia , Análise Custo-Benefício , Adulto , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos Ambulatórios/efeitos adversos , Ablação por Cateter/efeitos adversos , Estudos de Coortes , Feminino , Átrios do Coração/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
INTRODUCTION: Predicting sudden cardiac death (SCD) is challenging as current risk predictors have significant limitations. Evaluating magnetocardiogram (MCG) parameters could be of great value and we plan to assess the capability of a new mobile unshielded MCG device in predicting SCD and ventricular arrhythmias (VA) in patients undergoing implantable cardioverter defibrillator (ICD) implantation. METHODS AND ANALYSIS: A prospective multicentre (University Hospitals Coventry and Warwickshire (UHCW) National Health Service (NHS) Trust/University Hospital North Midlands NHS Trust, UK) observational study evaluating the VitalScan MCG (Creavo Medical Technologies, UK) to predict future VA risk; 270 patients meeting criteria for primary or secondary prevention ICDs (ischaemic or non-ischaemic aetiology) are being recruited. The first patient was recruited September 2019 and the study will be completed at final participant follow-up. The primary endpoint is appropriate ICD therapy for VA, secondary endpoint is SCD. Previous trials using MCG identified late QRS signals/QRS fragmentation as potential indicators of SCD in small samples using large shielded expensive MCG devices that were difficult to use clinically. It is hoped the MAGNETO-SCD trial will show this new MCG device can provide real world risk stratification for SCD/VA risk. The trial has recruited 25 patients (13 with secondary prevention indication) from a single site (UHCW) with recruitment starting at the second site in March 2020. ETHICS AND DISSEMINATION: Research Ethics Committee, Yorkshire and Humber Sheffield Research Ethics Committee UK (Ref: 19/YH/0143) and Health Research Authority (IRAS reference 254466, EDGE ID: 123146) approval received on 17/07/2019. The Medicines and Healthcare products Regulatory Agency approval received 11/07/2019. Results will be disseminated via a peer-reviewed publication and presentation at international conferences. TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov Registry (NCT04352816) and EU Clinical Trials Registry (EudraCT2019-002994-78).