Previous genome-wide association studies have demonstrated that single nucleotide polymorphisms in T‑box (TBX)5 are associated with increased susceptibility to atrial fibrillation (AF), and a recent study has causally linked a TBX5 mutation to atypical Holt-Oram syndrome and paroxysmal AF.
We speculate that the gain-of-function mechanism underlies the mild skeletal phenotype and paroxysmal atrial fibrillation and suggest a possible role of TBX5 in the development of (paroxysmal) atrial fibrillation based on a gain-of-function either through a direct stimulation of target genes via TBX5 or indirectly via TBX5 stimulated TBX3.
We functionally analyzed a frameshift mutation in the SCN5A gene encoding cardiac Na(+) channels (Nav1.5) found in a proband with repeated episodes of ventricular fibrillation who presented bradycardia and paroxysmal atrial fibrillation.
Paroxysmal atrial fibrillation (AF) can be caused by gain-of-function mutations in genes, encoding the cardiac potassium channel subunits KCNJ2, KCNE1, and KCNH2 that mediate the repolarizing potassium currents I<sub>k1</sub>, I<sub>ks</sub>, and I<sub>kr</sub>, respectively.
Protein levels for the L-type Ca(2+) channel and 5 potassium channels (Kv4.3, Kv1.5, HERG, minK, and Kir3.1) were significantly reduced in both persistent and paroxysmal AF.
Patients with paroxysmal atrial fibrillation had significantly elevated levels of P -selectin (p = 0.005) and fibrinogen (p = 0.003), but not von Willebrand factor (p =.0.61) compared to controls.
We genotyped ZFHX3 SNP rs2106261 and compared the minor (T) allele frequency between 362 paroxysmal AF (PAF) patients underwent pulmonary vein isolation (PVI) and 627 non-AF controls.
Since the proband developed paroxysmal AF at a young age, we screened 17 polymorphisms associated with AF risk in this family and showed that the proband carries at-risk polymorphisms upstream of PITX2, a gene widely associated with AF development.
The TGF-β1, Smad3 and IL-6 mRNA and protein expression levels in patients with AF were significantly higher than that in the control group (P<0.05), but there was no significantly different between the paroxysmal AF group and the persistent AF group (P>0.05).
IL-6 levels and MMP-9/TIMP-1 ratio were significantly higher in AF patients than in non-AF controls (P < .001), and in persistent than in paroxysmal AF (P < .001), in line with NT-proBNP and LA diameter.
Further, neutrophil/lymphocyte (N/L) ratio, C-reactive protein (CRP), and interleukin-6 (IL-6) expression levels were lower in PAF patients with the ZFHX3 SNP rs2106261 minor allele (TT+TC) than in CC patients (N/L ratio: CC 2.22 ± 0.08, TT+TC 1.98 ± 0.06, p = 0.018; CRP: CC 0.103 ± 0.009 mg/dl, TT+TC 0.076 ±0.007 mg/dl, p = 0.016; IL-6: CC 60.3 ± 3.0 pg/ml, TT+TC 52.8 ± 2.3 pg/ml, p = 0.04).
We sought to assess the association of baseline covariates with clinical outcomes in the 750 patients with drug-refractory paroxysmal AF enrolled in FIRE AND ICE.
The Impact of Cryoballoon Versus Radiofrequency Ablation for Paroxysmal Atrial Fibrillation on Healthcare Utilization and Costs: An Economic Analysis From the FIRE AND ICE Trial.
Recent studies have shown that the level of RyR2 protein is elevated in atria of patients with paroxysmal AF, suggesting that microRNA-mediated post-transcriptional regulation of RyR2 might be an underlying mechanism.
Patients with persistent/permanent AF more frequently had elevated renin than patients with paroxysmal AF (34.1% vs 15.8%; P = .007).This prospective study of consecutive cardiac disease patients referred for cardiac catheterization has revealed distinct cardiac disease condition-associated differences in the frequencies of elevations in plasma renin, PAC, and the aldosterone-renin ratio.
Regression analysis revealed that TGF-β1 was a major risk factor for AF recurrence (odds ratio, 1.14; 95% confidence interval, 1.11-1.17; P = .02).Serum TGF-β1 concentration is an independent predictor of AF recurrence in patients with paroxysmal AF and may help identify patients likely to have better outcomes after catheter ablation.
Patients with PAF were more likely to receive treatment with amiodarone (31.6% vs 13.8%, p < 0.001) and antiplatelet agents (54.1% vs 42.5%, p = 0.041) but less likely to receive treatment with renin-angiotensin system blockers (52.3% vs 64.9%, p = 0.021) and anticoagulants (33.3% vs 50%, p = 0.003) compared with patients with N-PAF at discharge.
Parkinson disease (PD), pure autonomic failure (PAF), and multiple system atrophy (MSA) are characterized by intra-cerebral deposition of the protein alpha-synuclein and are termed synucleinopathies.
A novel mutation in the RYR2 gene leading to catecholaminergic polymorphic ventricular tachycardia and paroxysmal atrial fibrillation: dose-dependent arrhythmia-event suppression by β-blocker therapy.
TGF-β1 was negatively correlated with NT-proBNP (r = -0.53, P = .001 in paroxysmal AF and r = -0.71, P < .001 in persistent AF) and LA diameter (r = -0.44, P = .006 in paroxysmal AF and r = -0.51, P = .003 in persistent AF).
While patients with PD, DLB, and MSA show both central and peripheral nervous system involvement of α-synuclein pathology, pure autonomic failure (PAF) is a condition characterized by generalized dysregulation of the autonomic nervous system with neuronal cytoplasmic α-synuclein inclusions in the peripheral autonomic small nerve fibers.
Patients with TIMP-1 < 107 ng/mL and no variant allele (GG) at rs10033464 had lower recurrence rates compared with other groups in those with paroxysmal AF (logrank; P = .007), whereas there was no significant difference among those patients with persistent forms of AF.