Evaluation of the left atrial substrate in patients with lone atrial fibrillation using delayed-enhanced MRI: implications for disease progression and response to catheter ablation.

BACKGROUND: Lone atrial fibrillation (AF) is thought to be a benign type or an early stage of the disease. OBJECTIVE: This study sought to compare the left atrium (LA) substrate using delayed-enhanced magnetic resonance imaging (DE-MRI) in patients with lone AF versus those with comorbidities. METHODS: Forty of 333 included patients met criteria for lone AF. All patients underwent DE-MRI to quantify atrial fibrosis as a marker for structural remodeling (SRM) and underwent catheter ablation. Based on the degree of SRM, patients were staged into 4 groups: Utah I (≤5% LA wall enhancement), Utah II (>5% to ≤20%), Utah III (>20% to ≤35%), or Utah IV (>35%). RESULTS: Distribution in Utah I to IV was comparable in patients with lone AF and non-lone AF. In both groups, a number of patients showed extensive SRM. Mean enhancement (14.08 ± 8.94 vs. 16.94 ± 11.37) was not significantly different between the 2 groups (P = .0721). In the lone AF group, catheter ablation was successful in suppressing AF in all of Utah I, 81.82% of Utah II, 62.5% of Utah III, and none of Utah IV patients. Similar results were achieved in the non-lone AF group. Outcome after ablation was significantly dependent on the SRM of the LA (P < .001). CONCLUSION: The degree of LA structural remodeling as detected using DE-MRI is independent of AF type and associated comorbidities. Selecting appropriate treatment candidates based on the quality and quantity of atrial fibrosis using DE-MRI would improve procedural outcome and avoid unnecessary intervention.

Displacement of Mn2+ from RNA by K+, Mg2+, neomycin B, and an arginine-rich peptide: indirect detection of nucleic acid/ligand interactions using phosphorus relaxation enhancement.

We have developed a novel method to study the interactions of nucleic acids with cationic species. The method, called phosphorus relaxation enhancement (PhoRE), uses (1)H-detected (31)P NMR of exogenous probe ions to monitor changes in the equilibrium between free Mn(2+) and Mn(2+) bound to the RNA. To demonstrate the technique, we describe the interactions of four RNA molecules with metal ions (K(+) and Mg(2+)), a small molecule drug (neomycin b), and a cationic peptide (RSG1.2). In each case, cationic ligand binding caused Mn(2+) to be displaced from the RNA. Free Mn(2+) was determined from its effect on the T(2) NMR relaxation rate of either phosphite (HPO(3)(2-)) or methyl phosphite (MeOPH, CH(3)OP(H)O(2-)). Using this method, the effects of [RNA] as low as 1 microM could be measured in 20 min of accumulation using a low field (200 MHz) instrument without pulsed field gradients. Cation association behavior was sequence and [RNA] dependent. At low [K(+)], Mn(2+) association with each of the RNAs decreased with increasing [K(+)] until approximately 40 mM, where saturation was reached. While saturating K(+) displaced all the bound Mn(2+) from a 31-nucleotide poly-uridine (U(31)), Mn(2+) remained bound to each of three hairpin-forming sequences (A-site, RRE1, and RRE2), even at 150 mM K(+). Bound Mn(2+) was displaced from each of the hairpins by Mg(2+), allowing determination of Mg(2+) dissociation constants (K(d,Mg)) ranging from 50 to 500 microM, depending on the RNA sequence and [K(+)]. Both neomycin b and RSG1.2 displaced Mn(2+) upon binding the hairpins. At [RNA] approximately 3 microM, RRE1 bound a single equivalent of RSG1.2, whereas neither RRE2 nor A-site bound the peptide. These behaviors were confirmed by fluorescence polarization using TAMRA-labeled peptide. At 2.7 microM RNA, the A-site hairpin bound a single neomycin b molecule. The selectivity of RSG1.2 binding was greatly diminished at higher [RNA]. Similarly, each hairpin bound multiple equivalents of neomycin at the higher [RNA]. These results demonstrate the utility of the PhoRE method for characterizing metal binding behaviors of nucleic acids and for studying RNA/ligand interactions.