Hypertension is a risk factor of atrial fibrillation (AF), and a certain number of patients with hypertension were found with an enlarged left atrium. Platelet activation is found in patients with hypertension or pressure overload/Ang II (angiotensin II)-induced hypertensive animal models and contribute to ventricular fibrosis. Whether hypertension-induced atrial fibrosis is mediated by platelets remains unknown. Our previous experimental data showed that platelet-derived TGF-β1 (transforming growth factor-β1) was reduced in patients with hypertensive AF. The present study is to investigate whether platelet-derived TGF-β1 promotes Ang II-induced atrial fibrosis and AF. Platelet activation and atrial platelet accumulation were measured in sinus rhythm controls, normotensive AF, and patients with hypertensive AF. Ang II (1500 ng/kg per minute, 3 weeks) infused mice with pharmacological (clopidogrel) and genetic platelet inhibition (TGF-β1 deletion in platelets) were used. Platelet activation, atrial structural remodeling, atrial electrical transmission, AF inducibility, inflammation, and fibrosis were measured in mice. We found that circulating platelets were activated in patients with hypertensive AF. A large amount of platelet was accumulated in the atriums of patients with hypertensive AF. Both clopidogrel treatment and platelet-specific deletion of TGF-β1 attenuated Ang II-induced structural remodeling, atrial electrical transmission, AF inducibility, as well as atrial inflammation and fibrosis than mice without interventions. Furthermore, clopidogrel blocked atrial platelet accumulation and platelet-fibroblast conjugation. Platelets promoted atrial fibroblast differentiation in cell culture. Profibrotic actions of platelets are largely via activation of atrial fibroblasts by releasing TGF-β1 and inducing platelet-fibroblast conjugation, and platelet inhibition is sufficient to inhibit atrial fibrosis and AF inducibility.

Doxorubicin therapy in mice (antitumor dosage) markedly enhanced platelet functions measured as agonist-induced platelet aggregation, degranulation, and adhesion to endothelial cells, actions leading to thrombus formation and thrombosis-independent vascular injury. Clopidogrel treatment ameliorated thrombus formation and vascular toxicity induced by doxorubicin via inhibiting platelet activity.

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BackgroundElectrocardiographic (ECG) characteristics of patients with isolated hypomagnesemia are not well defined. We aimed to investigate these ECG characteristics in order to define clearly the features of isolated hypomagnesemia.HypothesisLower serum magnesium could affect ECG parameters after excluding potential confounders.MethodsThis retrospective study was of patients with low serum magnesium <0.65 mmol/L compared with the same patients after restoration to normal serum magnesium. Patients with hypokalemia, hypocalcemia and other electrolyte disturbances were excluded. ECG parameters manually determined and analyzed were P wave dispersion, PR interval, QRS duration, ST-T changes, T wave amplitude, T peak-to-end interval (Tpe), corrected Tpe (Tpec), QT, corrected QT (QTc), QT peak corrected (QTpc) and Tpe dispersion, Tpe/QT ratio.ResultsTwo-hundred-and-fourteen patients with isolated hypomagnesemia were identified with 50 of them (56.9 ± 13.6 years; 25 males) being eligible for final analysis from 270,997 patients presenting April 2011–October 2017. In the period of isolated hypomagnesemia, P wave duration was found prolonged (p ≤ 0.02); as was QTc (439 ± 27 vs. 433 ± 22, p = 0.01). Tpec (122 ± 24vs. 111 ± 22, p = 0.000) and Tpe/QT ratio (0.29 ± 0.05 vs. 0.27 ± 0.05, p = 0.000) were increased. QTpc decreased during hypomagnesemia (334 ± 28 vs. 342 ± 21, p = 0.02). However, no significant differences were found in PR interval, QRS duration (85 ± 12 ms vs. 86 ± 12 ms, p = 0.122) and ST-T segments between the patients and their own controls.ConclusionsIn patients with isolated hypomagnesemia, P wave duration, QTc, Tpec, and Tpe/QT ratio suggesting atrial depolarization and ventricular repolarization dispersion were significantly increased compared with normal magnesium levels in the same patients after restoration to normal levels.

Objective: A more extensively fibrotic left atrium contributes to atrial fibrillation (AF) occurrence, persistence, and recurrence. The soluble suppression of tumorigenicity 2 (sST2) has emerged as a ventricular fibrotic biomarker for patients with heart failure. The present study is to investigate associations between circulating sST2 and risk of recurrence after ablation in AF patients.Methods: We measured the baseline plasma level of sST2 from patients with persistent AF (n = 117) and paroxysmal AF (n = 93) patients. Patients were followed up for 15 months after ablation. The relationship between circulating sST2 and recurrence was assessed by multivariable Cox regression. The cutoff value of sST2 was determined by receiver operating characteristic curve. The relationship between baseline sST2 level and left atrial volume index (LAVI) was assessed by multivariate linear regression analysis. Serial sST2 measurements were also conducted after 24 h, 6 months, and 15 months of ablation. ST2 localization was examined in left atrial appendages of persistent AF patients by immunohistochemistry and Western blot.Results: Baseline sST2 positively associated with LAVI in the persistent AF group, and elevated sST2 (≥39.25 ng/ml) independently increased the risk of recurrence after ablation (area under the curve = 0.748), with hazard ratio of 1.038 (95% confidence interval 1.017–1.060, P < 0.001) when adjusted for co-variables. In contrast, elevated sST2 cannot predict recurrence in paroxysmal AF.Conclusions: In persistent AF patients, increased sST2 serves as a marker of recurrence after radiofrequency ablation. Patients with sST2 ≥ 39.25 ng/ml are more likely to develop recurrence within a year.