RESUMO
BACKGROUND: The finding of unexpected variations in treatment benefits by geographic region in international clinical trials raises complex questions about the interpretation and generalizability of trial findings. We observed such geographical variations in outcome and in the effectiveness of atrial fibrillation (AF) ablation versus drug therapy in the Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation (CABANA) trial. This paper describes these differences and investigates potential causes. METHODS: The examination of treatment effects by geographic region was a prespecified analysis. CABANA enrolled patients from 10 countries, with 1,285 patients at 85 North American (NA) sites and 919 at 41 non-NA sites. The primary endpoint was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Death and first atrial fibrillation recurrence were secondary endpoints. RESULTS: At least 1 primary endpoint event occurred in 157 patients (12.2%) from NA and 33 (3.6%) from non-NA sites over a median 54.9 and 40.5 months of follow-up, respectively (NA/non-NA adjusted hazard ratio (HR) 2.18, 95% confidence interval (CI) 1.48-3.21, P < .001). In NA patients, 78 events occurred in the ablation and 79 in the drug arm, (HR 0.91, 95% CI 0.66, 1.24) while 11 and 22 events occurred in non-NA patients (HR 0.51, 95% CI 0.25,1.05, interaction Pâ¯=â¯.154). Death occurred in 53 ablation and 51 drug therapy patients in the NA group (HR 0.96, 95% CI 0.65,1.42) and in 5 ablation and 16 drug therapy patients in the non-NA group (HR 0.32, 95% CI 0.12,0.86, interaction Pâ¯=â¯.044). Adjusting for baseline regional differences or prognostic risk variables did not account for the regional differences in treatment effects. Atrial fibrillation recurrence was reduced by ablation in both regions (NA: HR 0.54, 95% CI 0.46, 0.63; non-NA: HR 0.44, 95% CI 0.30, 0.64, interaction Pâ¯=â¯.322). CONCLUSIONS: In CABANA, primary outcome events occurred significantly more often in the NA group but assignment to ablation significantly reduced all-cause mortality in the non-NA group only. These differences were not explained by regional variations in procedure effectiveness, safety, or patient characteristics. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT0091150; https://clinicaltrials.gov/study/NCT00911508.
Assuntos
Fibrilação Atrial , Ablação por Cateter , Parada Cardíaca , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/cirurgia , Antiarrítmicos/uso terapêutico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/complicações , Hemorragia/etiologia , Parada Cardíaca/etiologia , Ablação por Cateter/métodos , Resultado do Tratamento , RecidivaRESUMO
The subcutaneous implantable cardioverter defibrillator (S-ICD) was developed as an alternative to the traditional transvenous implantable cardioverter defibrillator (TV-ICD), aiming to provide easier implantation, simplified detection algorithm of malignant ventricular arrhythmias and prevention from placing components in the cardiovascular system. The S-ICD is implanted subcutaneously or intramuscularly with the generator placed in the left midaxillary line and the lead tunneled subcutaneously in the left para-sternal region. Preimplant electrocardiogram screening is recommended to prevent implantation in patients at high risk of T wave over-sensing. Currently, the S-ICD is unsuitable for patients requiring pacing or cardiac resynchronization. Since the beginning, the S-ICD underwent extensive preclinical investigation until the first prospective multicentre trial demonstrating high efficacy and safety led to market release. While earlier studies focused on younger patients with higher ejection fraction, more recent studies showed favorable outcomes even in patients with comorbidities similar to those typically observed in patients receiving TV-ICD. The development of second and third generation devices has contributed to reduce inappropriate shocks and overcome previous limitations. The aim of this paper is to review the evidence in the literature over the past decade supporting S-ICD as a valid alternative to TV-ICD in terms of safety and efficacy, highlighting the improvements in technology, as well as outcomes.
Assuntos
Morte Súbita Cardíaca , Desfibriladores Implantáveis , Humanos , Morte Súbita Cardíaca/prevenção & controle , Estudos Prospectivos , Resultado do Tratamento , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/terapia , Arritmias Cardíacas/etiologia , Desfibriladores Implantáveis/efeitos adversos , Estudos Multicêntricos como AssuntoRESUMO
Liver and heart disease are major causes of death worldwide. It is known that metabolic alteration causing type 2 diabetes (T2D) and Nonalcoholic fatty liver (NAFLD) coupled with a derangement in lipid homeostasis, may exacerbate hepatic and cardiovascular diseases. Some pharmacological treatments can mitigate organ dysfunctions but the important side effects limit their efficacy leading often to deterioration of the tissues. It needs to develop new personalized treatment approaches and recent progresses of engineered RNA molecules are becoming increasingly viable as alternative treatments. This review outlines the current use of antisense oligonucleotides (ASOs), RNA interference (RNAi) and RNA genome editing as treatment for rare metabolic disorders. However, the potential for small non-coding RNAs to serve as therapeutic agents for liver and heart diseases is yet to be fully explored. Although miRNAs are recognized as biomarkers for many diseases, they are also capable of serving as drugs for medical intervention; several clinical trials are testing miRNAs as therapeutics for type 2 diabetes, nonalcoholic fatty liver as well as cardiac diseases. Recent advances in RNA-based therapeutics may potentially facilitate a novel application of miRNAs as agents and as druggable targets. In this work, we sought to summarize the advancement and advantages of miRNA selective therapy when compared to conventional drugs. In particular, we sought to emphasise druggable miRNAs, over ASOs or other RNA therapeutics or conventional drugs. Finally, we sought to address research questions related to efficacy, side-effects, and range of use of RNA therapeutics. Additionally, we covered hurdles and examined recent advances in the use of miRNA-based RNA therapy in metabolic disorders such as diabetes, liver, and heart diseases.
Assuntos
Diabetes Mellitus Tipo 2 , Cardiopatias , Doenças Metabólicas , MicroRNAs , Hepatopatia Gordurosa não Alcoólica , Humanos , MicroRNAs/genética , MicroRNAs/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/genética , Oligonucleotídeos Antissenso/uso terapêuticoRESUMO
Atrial fibrillation (AF) represents the most common arrhythmia in clinical practice, characterized by irregular atrial electrical activity originating mainly in and around the pulmonary veins. This condition can manifest itself symptomatically or silently but still dangerously. Complications associated with AF include stroke, heart failure, worst clinical outcome in patients with underlying conditions, increased emergency room visits, hospitalizations, and cardiovascular mortality. Currently, according to the main international guidelines, antiarrhythmic therapy is considered the first choice for rhythm control in patients with AF despite modest efficacy and non-negligible side effects. In recent decades, radiofrequency catheter ablation has emerged as an alternative to antiarrhythmic drugs for rhythm control. Cryoablation was developed with the aim of reducing procedural times and reducing complications related to the ablative procedure with radiofrequency without losing efficacy. Recent studies conducted with rigour and scientific solidity have demonstrated on the one hand that the results of this technique are not inferior compare with radiofrequency. This study aims to compare data on the safety and efficacy of cryoablation with those obtained from antiarrhythmic drugs through a review of the most recent scientific evidence.
Assuntos
Fibrilação Atrial , Ablação por Cateter , Fibrilação Atrial/cirurgia , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Humanos , Ablação por Cateter/normas , Resultado do Tratamento , Consenso , Europa (Continente) , Cardiologia/normas , Medicina Baseada em Evidências/normasAssuntos
Apêndice Atrial , Fibrilação Atrial , Insuficiência Renal Crônica , Tromboembolia , Humanos , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/complicações , Apêndice Atrial/fisiopatologia , Tromboembolia/prevenção & controle , Tromboembolia/etiologia , Insuficiência Renal Crônica/complicações , Anticoagulantes/uso terapêutico , Fatores de Risco , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/etiologia , Resultado do TratamentoRESUMO
Aims: Catheter ablation is the most effective rhythm-control option in patients with atrial fibrillation (AF) and is currently considered an option mainly for improving symptoms. We aimed to assess the impact of catheter ablation on hard clinical outcomes. Methods and results: We performed a systematic review of randomized controlled trials (RCTs) comparing catheter ablation vs. optimized medical treatment. We searched MEDLINE, EMBASE, and CENTRAL on 8 January 2024, for trials published ≤10 years. We pooled data through risk ratio (RR) and mean differences (MDs), with 95% confidence interval (CI), and calculated the number needed to treat (NNT). Sub-group and sensitivity analyses were performed for the presence/absence of heart failure (HF), paroxysmal/persistent AF, early ablation, higher/lower quality, and published ≤5 vs. >5 years. Twenty-two RCTs were identified, including 6400 patients followed for 6-52 months. All primary endpoints were significantly reduced by catheter ablation vs. medical management: all-cause hospitalization (RR = 0.57, 95% CI 0.39-0.85, P = 0.006), AF relapse (RR = 0.48, 95% CI 0.39-0.58, P < 0.00001), and all-cause mortality (RR = 0.69, 95% CI 0.56-0.86, P = 0.0007, NNT = 44.7, driven by trials with HF patients). A benefit was also demonstrated for all secondary endpoints: cardiovascular mortality (RR = 0.55, 95% CI 0.34-0.87), cardiovascular (RR = 0.83, 95% CI 0.71-0.96), and HF hospitalizations (RR = 0.71, 95% CI 0.56-0.89), AF burden (MD = 20.6%, 95% CI 5.6-35.5), left ventricular ejection fraction (LVEF) recovery (MD = 5.7%, 95% CI 3.5-7.9), and quality of life (MLHFQ, AFEQT, and SF-36 scales). Conclusion: Catheter ablation significantly reduced hospitalizations, AF burden, and relapse, and improved quality of life. An impact on hard clinical outcomes, with an important mortality reduction and improvement in LVEF, was seen for patients with AF and HF.