Cardiovascular and renal effects of SGLT2 inhibitor initiation in acute heart failure: a meta-analysis of randomized controlled trials.

BACKGROUND: We sought to compare cardiovascular outcomes, renal function, and diuresis in patients receiving standard diuretic therapy for acute heart failure (AHF) with or without the addition of SGLT2i. METHODS AND RESULTS: Systematic search of three electronic databases identified nine eligible randomized controlled trials involving 2,824 patients. The addition of SGLT2i to conventional therapy for AHF reduced all-cause death (odds ratio [OR] 0.75; 95% CI 0.56-0.99; p = 0.049), readmissions for heart failure (HF) (OR 0.54; 95% CI 0.44-0.66; p < 0.001), and the composite of cardiovascular death and readmissions for HF (hazard ratio 0.71; 95% CI 0.60-0.84; p < 0.001). Furthermore, SGLT2i increased mean daily urinary output in liters (mean difference [MD] 0.45; 95% CI 0.03-0.87; p = 0.035) and decreased mean daily doses of loop diuretics in mg of furosemide equivalent (MD -34.90; 95% CI [- 52.58, - 17.21]; p < 0.001) without increasing the incidence worsening renal function (OR 0.75; 95% CI 0.43-1.29; p = 0.290). CONCLUSION: SGLT2i addition to conventional diuretic therapy reduced all-cause death, readmissions for HF, and the composite of cardiovascular death or readmissions for HF. Moreover, SGLT2i was associated with a higher volume of diuresis with a lower dose of loop diuretics.

Validation of a Smartphone Application in the Evaluation and Treatment of Acute Stroke in a Comprehensive Stroke Center.

Background and Purpose- The increasing demand and shortage of experts to evaluate and treat acute stroke patients has led to the development of remote communication tools to aid stroke management. We aimed to evaluate the JOIN App smartphone system-a low-cost tool for rapid clinical and neuroimaging data sharing to expedite decision-making in stroke. Methods- Consecutive acute ischemic stroke patients treated at a University Hospital in Brazil from December 2014 to December 2015 were evaluated. The analysis included all patients presenting with acute ischemic stroke who underwent initial evaluation by neurology residents followed by JOIN teleconsultation with a stroke neurologist on call for management decisions. An expert panel of stroke neurologists and neuroradiologists revised all cases using a standard Picture Archiving and Communication System imaging workstation within 24 hours and analyzed the decision made with remote assistance during the emergency setting. Results- A total of 720 stroke codes were evaluated with 442 acute ischemic stroke qualifying. Seventy-eight (18%) patients were treated with intravenous thrombolysis. The main reasons for tPA (tissue-type plasminogen activator) exclusion were symptom onset >4.5 hours (n=295; 67%) and hypodense middle cerebral artery territory area >1/3 (n=31; 7%). The agreement rates between Picture Archiving and Communication System versus JOIN-based thrombolysis decisions were 100% for the stroke (unblinded) and 99.3% for the neuroradiologist (blinded) experts. The use of the application resulted in a significant reduction in the door-to-needle times across the pre- versus postimplementation periods (median, 90 [interquartile range, 75-106] versus 63 [interquartile range, 61-117] minutes; P=0.03). The rates of 90-day excellent outcomes (modified Rankin Scale, 0-1) were 51.3%; 90-day mortality, 2.6%; and symptomatic intracranial hemorrhage, 3.8%. Conclusions- The JOIN smartphone system allows rapid sharing of clinical and imaging data to facilitate decisions for stroke treatment. The remote application-based decisions seem to be as accurate as the physical presence of stroke experts and might lead to faster times to treatment. This system represents an easily implementable low-cost telemedicine solution for centers that cannot afford the full-time presence of stroke specialists.

Ablation strategies for the management of symptomatic Brugada syndrome: A systematic review.

BACKGROUND: Ablation approaches have been described for the management of symptomatic ventricular arrhythmias in patients with Brugada syndrome, but this treatment is still considered experimental. OBJECTIVE: We aimed to perform a systematic review of the current evidence on the use of catheter ablation in Brugada syndrome. METHODS: MEDLINE, Embase, and Scopus were searched for articles describing the use of catheter ablation for ventricular arrhythmia management in Brugada syndrome. RESULTS: We included 11 case series and 11 case reports including a total of 233 patients. Ablation strategies included epicardial mapping with substrate modification (n = 180; 77.3%), endocardial-only mapping with substrate modification (n = 17; 7.3%), ventricular fibrillation (VF)-triggering premature ventricular complex ablation (n = 5; 2.1%), and mixed approaches (n = 31; 13.3%). During a 2.5- to 78-month follow-up period, the success rates in preventing ventricular tachycardia or VF (VT/VF) were 96.7%, 70.6%, and 80% with epicardial, endocardial, and triggering premature ventricular complex ablation approaches, respectively. Among patients who underwent both epicardial and endocardial mapping, there was no identifiable endocardial substrate in 92.9% of cases. Elimination of type 1 Brugada-pattern electrocardiogram was attained in 98.3% and 34.8% of the epicardial and endocardial ablation groups, respectively. VT/VF occurred in 7 of 9 patients (77.8%) who had persistent or recurrent J-ST elevation and in none of the 24 patients with complete resolution during follow-up. Pharmacologic provocation augmented the abnormal area. CONCLUSION: Epicardial substrate modification appears to be more effective than endocardial-only approach in preventing VT/VF. Persistent or recurrent J-ST elevation appears to represent a marker of failure of ablation. Ablation seems to be an acceptable strategy for patients with Brugada syndrome and VT/VF.

An updated meta-analysis of novel oral anticoagulants versus vitamin K antagonists for uninterrupted anticoagulation in atrial fibrillation catheter ablation.

BACKGROUND: Catheter ablation is recommended as a first- or second-line rhythm control therapy for selected patients with atrial fibrillation (AF). There is a wide variability in the periprocedural management of oral anticoagulation in patients undergoing AF ablation. OBJECTIVE: We aimed to perform an updated meta-analysis of novel oral anticoagulants (NOACs) vs vitamin K antagonists (VKAs) as uninterrupted anticoagulation in patients undergoing AF ablation. METHODS: Databases and conference abstracts were searched. Studies were excluded if oral anticoagulants were held at any periprocedural period. The primary outcomes were stroke or transient ischemic attack (TIA) and major bleeding. RESULTS: Twelve studies and 4962 patients were included. Stroke or TIA was rare (NOAC, 0.08%; VKA, 0.16%) and not different between groups (odds ratio [OR] 0.66; 95% confidence interval [CI] 0.19-2.30). The incidence of silent cerebral embolic events was also not significantly different between NOACs (8%) and VKAs (9.6%) (OR 0.86; 95% CI 0.42-1.76). Major bleeding was significantly reduced in the NOAC group (0.9%) as compared with VKA-treated patients (2%) (OR 0.50; 95% CI 0.30-0.84; P < .01). This finding was confirmed in a subgroup analysis of randomized and cohort studies with matched controls (OR 0.45; 95% CI 0.24-0.83; P = .01). There was no significant difference in the outcomes of individual NOACs and VKAs, although these analyses may have been underpowered to detect minor differences in such rare outcomes. CONCLUSION: In patients undergoing AF ablation, uninterrupted periprocedural NOACs are associated with a low incidence of stroke or TIA and a significant reduction in major bleeding as compared with uninterrupted VKAs.

Efetividade da Terapia Medicamentosa e dos Procedimentos de Revascularização como Estratégia Inicial na Doença Arterial Coronariana Estável: Estudo de Coorte / Effectiveness of Medical and Revascularization Procedures as the Initial Strategy in Stable Coronary Artery Disease: A Cohort Study

Fundamento: A cirurgia de revascularização miocárdica (CRM) e a intervenção coronária percutânea (ICP) são estratégias amplamente utilizadas no manejo da doença arterial coronariana (DAC) estável. Objetivo: Avaliar o prognóstico de pacientes com DAC estável inicialmente tratada com terapia médica (TM), em comparação com os pacientes submetidos a procedimentos de revascularização. Métodos: Estudo prospectivo de coorte com 560 pacientes ambulatoriais de um hospital terciário com seguimento médio de 5 anos. Os pacientes foram classificados nos grupos TM (n = 288), ICP (n = 159) e CRM (n = 113) de acordo com sua estratégia inicial de tratamento. Os desfechos primários foram mortalidade global e eventos combinados de morte, síndrome coronária aguda e AVC. Resultados: Durante o seguimento, as taxas de mortalidade foram de 11,1% em TM, 11,9% em ICP e 15,9% em pacientes submetidos à CRM, sem diferença estatística (Hazard Ratio [HR] para ICP, 1,05; Intervalo de Confiança de 95% [IC95%], 0,59 a 1,84; e HR para CRM, 1,20; IC95%, 0,68 a 2,15). Os desfechos combinados ocorreram com maior frequência entre os pacientes inicialmente submetidos à ICP em relação à TM (HR 1,50, IC 95% 1,05 a 2,14) e não diferiram entre TM e CRM (HR 1,24, IC95% 0,84 a 1,83). Entre os pacientes com diabetes (n = 198), a ICP foi a única estratégia terapêutica preditiva de desfechos combinados (HR 2,14; IC 95%: 1,25 a 3,63). Conclusão: Neste estudo observacional de doença arterial coronariana estável, não houve diferença na mortalidade global entre as estratégias iniciais de terapia médico ou de cirurgia de revascularização. Os pacientes inicialmente tratados com ICP tiveram maior chance de desenvolver eventos cardiovasculares maiores combinados

Background: Coronary artery bypass grafting surgery (CABG) and percutaneous coronary intervention (PCI) are widely-used strategies in the management of stable coronary artery disease (CAD). Objective: To evaluate the prognosis of patients with stable CAD initially treated by medical therapy (MT), compared to the patients who were submitted to revascularization procedures. Methods: We conducted a prospective cohort study of 560 patients from an outpatient clinic in a tertiary hospital, with a mean follow-up of 5 years. Patients were classified into MT (n = 288), PCI (n = 159) and CABG (n=113) groups according to their initial treatment strategy. Primary endpoints were overall mortality and combined events of death, acute coronary syndrome, and stroke. Results: During follow-up, death rates were 11.1% in MT, 11.9% in PCI and 15.9% in CABG patients, with no statistical difference (hazard ratio [HR] for PCI, 1.05; 95% confidence interval [95%CI], 0.59 to 1.84; and HR for CABG, 1.20; 95% CI: 0.68 to 2.15). Combined outcomes occurred more often among patients initially submitted to PCI compared to MT (HR 1.50, 95% CI 1.05 to 2.14), and did not differ between MT and CABG patients (HR 1.24, 95% CI 0.84 to 1.83). Among patients with diabetes (n=198), PCI was the only therapeutic strategy predictive of combined outcomes (HR 2.14; 95% CI 1.25 to 3.63). Conclusion: In this observational study of stable coronary artery disease, there was no difference in overall mortality between initial medical therapy or revascularization surgery strategies. Patients initially treated with PCI had greater chance to develop combined major cardiovascular events

Pyruvate and creatine prevent oxidative stress and behavioral alterations caused by phenylalanine administration into hippocampus of rats.

Phenylketonuria is characterized by a variable degree of mental retardation and other neurological features whose mechanisms are not fully understood. In the present study we investigated the effect of intrahippocampal administration of phenylalanine, isolated or associated with pyruvate or creatine, on rat behavior and on oxidative stress. Sixty-day-old male Wistar rats were randomly divided into 6 groups: saline; phenylalanine; pyruvate; creatine; phenylalanine + pyruvate; phenylalanine + creatine. Phenylalanine was administered bilaterally in the hippocampus one hour before training; pyruvate, at the same doses, was administered in the hippocampus one hour before phenylalanine; creatine was administered intraperitoneally twice a day for 5 days before training; controls received saline solution at same volumes than the other substances. Parameters of exploratory behavior and of emotionality were assessed in both training and test sessions in the open field task. Rats receiving phenylalanine did not habituate to the open field along the sessions, indicating deficit of learning/memory, but parameters of emotionality were normal, not interfering in the habituation process. Pyruvate or creatine administration prevented the lack of habituation caused by phenylalanine. Pyruvate and creatine also prevented alterations provoked by phenylalanine on lipid peroxidation, total content of sulfhydryls, total radical-trapping antioxidant potential and total antioxidant reactivity. The results suggest that the behavioral alterations provoked by intra-hippocampal administration of phenylalanine may be caused, at least in part, by oxidative stress and/or energy deficit. If this also occurs in PKU, it is possible that pyruvate and creatine supplementation to the phenylalanine-restricted diet might be beneficial to phenylketonuric patients.