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.
Objective
To determine whether abnormalities of calcium cycling explain ventricular action potential (AP) oscillations and cause ECG T-wave Alternans (TWA).
Background
Mechanisms explaining why heart failure patients are at risk for malignant ventricular arrhythmias (VT/VF) are unclear. We studied whether oscillations in human ventricular AP explain TWA and predict VT/VF, and used computer modeling to suggest potential cellular mechanisms.
Methods
We studied 53 patients with LV ejection fraction 28±8% and 18 control subjects. Monophasic AP were recorded in the right (RV, n=62) and/or left (LV, n=9) ventricle at 109 beats/min.
Results
Alternans of AP amplitude, computed spectrally, had higher magnitude in study patients than controls (p=0.03), particularly in AP phase II (p=0.02) rather than phase III (p=0.10). APD and activation restitution (n=11 patients) were flat at 109 beats/min and did not explain TWA. In computer simulations, only reduced sarcoplasmic reticulum calcium uptake explained our results, causing causing calcium oscillations, AP amplitude alternans and TWA that were all abolished by calcium clamping. On prospective follow-up for 949±553 days, 17 patients suffered VT/VF. AP amplitude alternans predicted VT/VF (p=0.04), and was 78% concordant with simultaneous TWA (p=0.003).
Conclusions
Patients with systolic dysfunction show ventricular AP amplitude alternans that prospectively predicted VT/VF. Alternans in AP amplitude, but not variations in APD or conduction, explained TWA at ≤109 beats/min. In computer models, these findings were best explained by reduced sarcoplasmic reticulum calcium uptake. In heart failure patients, in vivo AP alternans may reflect cellular calcium abnormalities and provide a mechanistic link with VT/VF.
The mechanism by which TWA predicts arrhythmic mortality does not reflect the maximum slope of ventricular APD restitution. Better understanding of the mechanisms underlying TWA may enable improved prediction and prevention of ventricular arrhythmias.
Background-Alternans in action potential voltage (APV-ALT) at heart rates <110 beats/min is a novel index to predict ventricular arrhythmias. However, the rate-dependency of APV-ALT and its mechanisms in failing versus non-failing human myocardium are poorly understood. It is hypothesized that APV-ALT in human heart failure (HF) reflects abnormal calcium handling.
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