Objectives To determine if ablation that targets patient-specific AF-sustaining substrates (rotors or focal sources) is more durable than trigger ablation alone at preventing late AF recurrences. Background Late recurrence substantially limits the efficacy of pulmonary vein (PV) isolation for AF, and is associated with PV reconnection and the emergence of new triggers. Methods We performed 3 year follow-up of the CONFIRM trial, in which 92 consecutive AF patients (70.7% persistent) underwent novel computational mapping to reveal a median of 2 (IQR 1–2) rotors or focal sources in 97.7% of patients during AF. Ablation comprised source (Focal Impulse and Rotor Modulation, FIRM) then conventional ablation in n=27 (FIRM-guided), and conventional ablation alone in n=65 (FIRM-blinded). Patients were followed with implanted ECG monitors when possible (85.2% FIRM guided, 23.1% FIRM-blinded). Results On 890 days follow-up (median; IQR 224–1563) compared FIRM-blinded therapy, patients receiving FIRM-guided ablation maintained higher freedom from AF after 1.2±0.4 procedures (median 1, IQR 1–1) (77.8% vs 38.5%; p=0.001) and a single procedure (p>0.001), and higher freedom from all atrial arrhythmias (p=0.003). Freedom from AF was higher when ablation directly or coincidentally passed through sources than when it missed sources (p>0.001). CONCLUSIONS FIRM-guided ablation is more durable than conventional trigger-based ablation at preventing 3 year AF recurrence. Future studies should investigate how ablation of patient-specific AF-sustaining rotors and focal sources alters the natural history of arrhythmia recurrence.

Although MR spectroscopic imaging (MRSI) of the prostate has demonstrated clinical utility for the staging and monitoring of cancer extent, current acquisition methods are often inadequate in several aspects. Conventional 180°pulses can suffer from chemical shift misregistration, and have high peak-power requirements that can exceed hardware limits in many prostate MRSI studies. Optimal water and lipid suppression are also critical to obtain interpretable spectra. While complete suppression of the periprostatic lipid resonance is desired, controlled partial suppression of water can provide a valuable phase and frequency reference for data analysis and an assessment of experimental success in cases in which all other resonances are undetectable following treatment. In this study, new spectral-spatial RF pulses were developed to negate chemical shift misregistration errors and to provide dualband excitation with partial excitation of the water resonance and full excitation of the metabolites of interest. Optimal phase modulation was also included in the pulse design to provide 40% reduction in peak RF power. Patient studies using the new pulses demon- Recently, 3D magnetic resonance spectroscopic imaging (MRSI) studies have demonstrated clinical utility for determining the location and spatial extent of cancer within the prostate (1-3) and its spread outside the gland (4). Prostate cancer can be metabolically identified with high specificity by an elevation in the choline-to-citrate peak area ratio relative to normal prostatic tissues. The high specificity of MRSI complements the high sensitivity of MRI for identifying cancer, and MRSI is now used routinely in clinical/research MR staging exams at our institution to provide a combined anatomic/metabolic assessment of prostate cancer extent. For the combined MRI/ MRSI prostate exam to be accepted in general clinical practice, robust acquisition techniques must be developed and implemented. The conventional point-resolved spectroscopy (PRESS) (5-7) technique is often limited by inadequate water or lipid suppression and chemical shift misregistration.Spectral-spatial excitation pulses (8 -11) have demonstrated the ability to address these problems (8,12). This type of RF pulse excites a slice, but only at a specific range of frequencies. They are also known as echo-planar spinecho (EPSE) pulses, because they use a gradient waveform that is essentially the same as echo-planar imaging (EPI). The spectral-spatial PRESS sequence uses two EPSE 180°p ulses to define both spatial and spectral profiles (8). However, the complete suppression of the water resonance provided by these pulses is undesirable for clinical MRSI since residual water signals can serve as valuable references for phase and frequency correction. The detection of residual water in each voxel is also critical for monitoring treatment response. Following hormone ablation or radiation therapy, choline, creatine, and citrate levels can decrease to noise levels (1,2). In these cases, the observation of residua...

Objectives The aim of this study was to determine whether onset sites of human atrial fibrillation (AF) exhibit conduction slowing, reduced amplitude, and/or prolonged duration of signals (i.e., fractionation) immediately before AF onset. Background Few studies have identified functional determinants of AF initiation. Because conduction slowing is required for reentry, we hypothesized that AF from pulmonary vein triggers might initiate at sites exhibiting rate-dependent slowing in conduction velocity (CV restitution) or local slowing evidenced by signal fractionation. Methods In 28 patients with AF (left atrial size 43 ± 5 mm; n = 13 persistent) and 3 control subjects (no AF) at electrophysiological study, we measured bi-atrial conduction time (CT) electrogram fractionation at 64 or 128 electrodes with baskets in left (n = 17) or both (n = 14) atria during superior pulmonary vein pacing at cycle lengths (CL) accelerating from 500 ms (120 beats/min) to AF onset. Results Atrial fibrillation initiated in 19 of 28 AF patients and no control subjects. During rate acceleration, conduction slowed in 23 of 28 AF patients (vs. no control subjects, p = 0.01) at the site of AF initiation (15 of 19) or latest activated site (20 of 28). The CT lengthened from 79 ± 23 ms to 107 ± 39 ms (p < 0.001) on acceleration, in a spectrum from persistent AF (greatest slowing) to control subjects (least slowing; p < 0.05). Three patterns of CV restitution were observed: 1) broad (gradual CT prolongation, 37% patients); 2) steep (abrupt prolongation, at CL 266 ± 62 ms, 42%); and 3) flat (no prolongation, 21% AF patients, all control subjects). The AF initiation was more prevalent in patients with CV restitution (17 of 23 vs. 2 of 8; p = 0.03) and immediately followed abrupt reorientation of the activation vector in patients with broad but not steep CV restitution (p < 0.01). Patients with broad CV restitution had larger atria (p = 0.03) and were more likely to have persistent AF (p = 0.04). Notably, neither amplitude nor duration (fractionation) of the atrial signal at the AF initiation site were rate-dependent (both p = NS). Conclusions Acceleration-dependent slowing of atrial conduction (CV restitution) precedes AF initiation, whereas absence of CV restitution identifies inability to induce AF. Conduction restitution, but not fractionated electrograms, may thus track the functional milieu enabling AF initiation and has implications for guiding AF ablation and pharmacological therapy.

Background It is unknown how atrial fibrillation (AF) is actually initiated by triggers. Based on consistencies in atrial structure and function in individual patients between episodes of AF, we hypothesized that human AF initiates when triggers interact with deterministic properties of the atria and may engage organized mechanisms. Methods and Results In 31 AF patients we mapped AF initiation after spontaneous triggers or programmed stimulation. We used 64-pole basket catheters to measure regional dynamic conduction slowing and to create bi-atrial activation maps during transitions to AF. Sixty-two AF initiations were recorded (spontaneous, n=28; induced, n=34). Notably, AF did not initiate by disorganized mechanisms, but by either a dominant reentrant spiral wave (76%) or a repetitive focal driver. Both mechanisms were located 21±17mm from their triggers. AF-initiating spirals formed at the site showing the greatest rate-dependent slowing in each patient. Accordingly, in 10/12 patients with multiple observed AF episodes, AF initiated using spatially conserved mechanisms despite diverse triggers. Conclusions Human AF initiates from triggers by organized rather than disorganized mechanisms, either via spiral wave reentry at sites of dynamic conduction slowing, or via repetitive focal drivers. The finding that diverse triggers initiate AF at predictable, spatially conserved functional sites in each individual provides a novel deterministic paradigm for AF with therapeutic implications.