Complexity and perplexity of pulsed field ablation

Pulsed field ablation (PFA), recently introduced as a non-thermal and selective method for cardiac ablation, was associated with great promise, hope and expectation, but also raised some concerns and left some questions unanswered, in particular with respect to waveform. To better understand the challenges associated with the design and development of safe and efficient PFA systems, the underlying mechanism of electroporation at the membrane, cellular and tissue levels is described. The three interdependent components of each system, that is, the waveform, the catheter and the generator, are then addressed. The effect of the different waveform parameters on treatment outcomes is reviewed, and the consequences of a potential mismatch of the three components in the development of a safe and efficient PFA system are highlighted.