BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) have emerged as potential therapy to target the underlying arrhythmogenic substrate in atrial fibrillation (AF). Nevertheless, there have been inconsistent results on the impact of MRAs on AF.
OBJECTIVE: We sought to evaluate the effect of MRAs on AF incidence and progression in patients with and without heart failure.
METHODS: Electronic databases were searched up to September, 2022 for randomized controlled trials (RCTs) that evaluated MRA use and reported AF outcomes. Primary outcome was a composite of new-onset or recurrent AF. Safety outcomes included hyperkalemia and gynecomastia risks. A random-effects meta-analysis estimated pooled odds ratios (OR) and 95% confidence intervals (CI).
RESULTS: 12 RCTs, comprising 11,419 patients treated with various MRAs were included [5960 (52%) on MRA]. On follow-up (6-39 months), 714 (5.5%) patients developed AF. MRA therapy was associated with a 32% reduction in the risk of new-onset or recurrent AF [OR 0.68 (95% CI 0.51-0.92), I2 = 40%]. On subgroup analysis, the greatest benefit magnitude was demonstrated in reducing AF recurrence [OR 0.50 (95% CI 0.30-0.83)] and among patients with left ventricular dysfunction [OR 0.59 (95% CI 0.40-0.85)]. Gynecomastia, but not hyperkalemia, was associated with MRA use. Meta-regression analysis demonstrated that therapy duration was a significant interaction factor driving the effect size (Pinteraction = 0.013).
CONCLUSIONS: MRA use is associated with a reduction in AF risk, especially AF progression. A prominent effect is seen in patients with heart failure, further augmented by therapy duration. Prospective trials are warranted to evaluate MRA use as upstream therapy for preventing this common arrhythmia.

OBJECTIVE: New drugs to block the occurrence of atrial fibrillation (AF) based on atrial structural remodeling (ASR) are urgently needed. The purpose of this study was to study the role of intermedin 1-53 (IMD1-53) in ASR and AF formation in rats after myocardial infarction (MI).
METHODS: Heart failure was induced by MI in rats. Fourteen days after MI surgery, rats with heart failure were randomized into control (untreated MI group, n = 10) and IMD-treated (n = 10) groups. The MI group and sham group received saline injections. The rats in the IMD group received IMD1-53, 10 nmol/kg/day intraperitoneally for 4 weeks. The AF inducibility and atrial effective refractory period (AERP) were assessed with an electrophysiology test. Additionally, the left-atrial diameter was determined, and heart function and hemodynamic tests were performed. We detected the area changes of myocardial fibrosis in the left atrium using Masson staining. To detect the protein expression and mRNA expression of transforming growth factor-β1 (TGF-β1), α-SMA, collagen Ⅰ, collagen III, and NADPH oxidase (Nox4) in the myocardial fibroblasts and left atrium, we used the Western blot method and real-time quantitative polymerase chain reaction (PCR) assays.
RESULTS: Compared with the MI group, IMD1-53 treatment decreased the left-atrial diameter and improved cardiac function, while it also improved the left-ventricle end-diastolic pressure (LVEDP). IMD1-53 treatment attenuated AERP prolongation and reduced atrial fibrillation inducibility in the IMD group. In vivo, IMD1-53 reduced the left-atrial fibrosis content in the heart after MI surgery and inhibited the mRNA and protein expression of collagen type Ⅰ and III. IMD1-53 also inhibited the expression of TGF-β1, α-SMA, and Nox4 both in mRNA and protein. In vivo, we found that IMD1-53 inhibited the phosphorylation of Smad3. In vitro, we found that the downregulated expression of Nox4 was partly dependent on the TGF-β1/ALK5 pathway.
CONCLUSIONS: IMD1-53 decreased the duration and inducibility of AF and atrial fibrosis in the rats after MI operation. The possible mechanisms are related to the inhibition of TGF-β1/Smad3-related fibrosis and TGF-β1/Nox4 activity. Therefore, IMD1-53 may be a promising upstream treatment drug to prevent AF.

BACKGROUND: Numerous clinical studies reported the effectiveness of herbal formula WuShen (WS) in treating cardiovascular diseases, yet relevant basic research was rarely conducted.
RESULTS: Twelve main bioactive compounds of WS decoction were identified using the ultra-performance liquid chromatography-LTQ-Orbitrap mass spectrometer. A total of 137 active compounds with 613 targets were predicted by network pharmacology; their bioinformatic annotation and human microarray data suggested that wounding healing, inflammatory response, and gap junction were potentially the major therapeutic modules. A rat model of post-myocardial infarction (MI) heart failure (HF) was used to study the effects of WS on cardiac function, adverse cardiac remodeling, and experimental arrhythmias. Rats treated with WS led to a significantly improved pump function and reduced susceptibility to both ventricular tachycardia and atrial fibrillation, and restricted adverse cardiac remodeling partly via inhibiting TGFβ1/SMADs mediated extracellular matrix deposition and Rac1/NOX2/CTGF/Connexin43 -involved gap junction remodeling.
CONCLUSIONS: The present study highlights that WS can be applied to the treatment of heart failure and the upstream therapy for atrial fibrillation and ventricular tachycardia through its preventive effect on adverse cardiac remodeling.

There are several non-genetic risk factors for new-onset atrial fibrillation, including age, sex, obesity, hypertension, diabetes, and alcohol consumption. However, whether these non-genetic risk factors have equal significance among different age groups is not known. We performed a nationwide population-based analysis to compare the clinical significance of non-genetic risk factors for new-onset atrial fibrillation in various age groups.
A total of 9,797,409 people without a prior diagnosis of atrial fibrillation who underwent a national health check-up in 2009 were included. During 80,130,090 person-years of follow-up, a total of 196,136 people were diagnosed with new-onset atrial fibrillation. The impact of non-genetic risk factors on new-onset atrial fibrillation was examined in different age groups. Obesity, male sex, heavy alcohol consumption, smoking, hypertension, diabetes and chronic kidney disease were associated with an increased risk of new-onset atrial fibrillation. With minor variations, these risk factors were consistently associated with the risk of new-onset atrial fibrillation among various age groups. Using these risk factors, we created a scoring system to predict future risk of new-onset atrial fibrillation in different age groups. In receiver operating characteristic curve analysis, the predictive value of these risk factors ranged between 0.556 and 0.603, and no significant trends were observed.
Non-genetic risk factors for new-onset atrial fibrillation may have a similar impact on different age groups. Except for sex, these non-genetic risk factors can be modifiable. Therefore, efforts to control non-genetic risk factors might have relevance for both the young and old.

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Atrial fibrillation (AF) is part of a vicious cycle that includes multiple cardiovascular risk factors and comorbidity which can promote atrial remodelling and AF progression. Most AF-related risk factors-hypertension, diabetes, sleep apnoea, obesity and sedentary lifestyle-are in essence modifiable which may prevent AF development. Treatment of associated cardiovascular conditions may prevent both symptoms and future cardiovascular events. For advanced forms of symptomatic AF refractory to lifestyle management and optimal medication, invasive ablation therapies have become a cornerstone. Although electrical trigger isolation from the pulmonary veins is reasonably effective and safe, more potent energy sources including high output-short duration radiofrequency, ultra-low cryo-energy, and electroporation, as well as more sophisticated arrays, balloons, and lattice-tipped catheter tools, are on their way to eliminate existing pitfalls and simplify the procedure. Electroanatomical navigation and mapping systems are becoming available to provide real-time information on ablation lesion quality and the critical pathways of AF in the individual patient to guide more extensive ablation strategies that may enhance long-term outcome for freedom of advanced AF. Surgical techniques, either stand-alone or concomitant to structural cardiac repair, hybrid, or convergent, with novel less invasive access options are developing and can be helpful in situations unsuitable for catheter ablation.

OBJECTIVE: There are several non-genetic risk factors for new-onset atrial fibrillation, including age, sex, obesity, hypertension, diabetes, and alcohol consumption. However, whether these non-genetic risk factors have equal significance among different age groups is not known. We performed a nationwide population-based analysis to compare the clinical significance of non-genetic risk factors for new-onset atrial fibrillation in various age groups.
RESULTS: A total of 9,797,409 people without a prior diagnosis of atrial fibrillation who underwent a national health check-up in 2009 were included. During 80,130,090 person-years of follow-up, a total of 196,136 people were diagnosed with new-onset atrial fibrillation. The impact of non-genetic risk factors on new-onset atrial fibrillation was examined in different age groups. Obesity, male sex, heavy alcohol consumption, smoking, hypertension, diabetes and chronic kidney disease were associated with an increased risk of new-onset atrial fibrillation. With minor variations, these risk factors were consistently associated with the risk of new-onset atrial fibrillation among various age groups. Using these risk factors, we created a scoring system to predict future risk of new-onset atrial fibrillation in different age groups. In receiver operating characteristic curve analysis, the predictive value of these risk factors ranged between 0.556 and 0.603, and no significant trends were observed.
CONCLUSIONS: Non-genetic risk factors for new-onset atrial fibrillation may have a similar impact on different age groups. Except for sex, these non-genetic risk factors can be modifiable. Therefore, efforts to control non-genetic risk factors might have relevance for both the young and old.

Heavy consumption of alcohol is a known risk factor for new-onset atrial fibrillation (AF). We aimed to evaluate the relative importance of frequent drinking vs. binge drinking.
A total of 9 776 956 patients without AF who participated in a national health check-up programme were included in the analysis. The influence of drinking frequency (day per week), alcohol consumption per drinking session (grams per session), and alcohol consumption per week were studied. Compared with patients who drink twice per week (reference group), patients who drink once per week showed the lowest risk [hazard ratio (HR) 0.933, 95% confidence interval (CI) 0.916-0.950] and those who drink everyday had the highest risk for new-onset AF (HR 1.412, 95% CI 1.373-1.453), respectively. However, the amount of alcohol intake per drinking session did not present any clear association with new-onset AF. Regardless of whether weekly alcohol intake exceeded 210 g, the frequency of drinking was significantly associated with the risk of new-onset AF. In contrast, when patients were stratified by weekly alcohol intake (210 g per week), those who drink large amounts of alcohol per drinking session showed a lower risk of new-onset AF.
Frequent drinking and amount of alcohol consumption per week were significant risk factors for new-onset AF, whereas the amount of alcohol consumed per each drinking session was not an independent risk factor. Avoiding the habit of consuming a low but frequent amount of alcohol might therefore be important to prevent AF.

Atria-selective antiarrhythmic drugs in need of alliance partners. Guideline-based treatment of atrial fibrillation (AF) comprises prevention of thromboembolism and stroke, as well as antiarrhythmic therapy by drugs, electrical rhythm conversion, ablation and surgical procedures. Conventional antiarrhythmic drugs are burdened with unwanted side effects including a propensity of triggering life-threatening ventricular fibrillation. In order to solve this therapeutic dilemma, \'atria-selective\' antiarrhythmic drugs have been developed for the treatment of supraventricular arrhythmias. These drugs are designed to aim at atrial targets, taking advantage of differences in atrial and ventricular ion channel expression and function. However it is not clear, whether such drugs are sufficiently antiarrhythmic or whether they are in need of an alliance partner for clinical efficacy. Atria-selective Na+ channel blockers display fast dissociation kinetics and high binding affinity to inactivated channels. Compounds targeting atria-selective K+ channels include blockers of ultra rapid delayed rectifier (Kv1.5) or acetylcholine-activated inward rectifier K+ channels (Kir3.x), inward rectifying K+ channels (Kir2.x), Ca2+-activated K+ channels of small conductance (SK), weakly rectifying two-pore domain K+ channels (K2P), and transient receptor potential channels (TRP). Despite good antiarrhythmic data from in-vitro and animal model experiments, clinical efficacy of atria-selective antiarrhythmic drugs remains to be demonstrated. In the present review we will briefly summarize the novel compounds and their proposed antiarrhythmic action. In addition, we will discuss the evidence for putative improvement of antiarrhythmic efficacy and potency by addressing multiple pathophysiologically relevant targets as possible alliance partners.