Professor Andrew Grace

Andrew has strengths in strategic thinking and execution that have contributed significantly to developing new transformative treatments. His research impact has coincided with, and also significantly influenced, an era of enhanced awareness of the impact of arrhythmias on health with a research programme designed at its outset both to increase biological understanding and also provide real world benefit. Patient safety has been central with knowledge arising from his University-based lab work influencing practice most prominently through drug regulation across both the UK and Europe.

In addition to ‘soft’ impacts several of his innovations, developed through interdisciplinary collaboration, have already provided direct patient benefit. He has progressed from analysing mechanisms of cardiac Na+-dependent proton efflux, to describing functional consequences of the disruption of genes implicated in arrhythmogenesis (in model systems) to quantifying cardiac excitation in complex disease. Specific contributions leading to significant change include:

(i) Subcutaneous defibrillators (SICDs) - Andrew completed ‘proof of concept’ studies and then implanted the first devices in the UK, Netherlands, Germany and Saudi Arabia and is last-named author on the New England Journal of Medicine paper describing the advance. SICDs have been adopted into international guidelines, implanted in >90,000 patients, are the first leadless cardiac devices, and received the 2013 Prix Galien in New York for best Medtech product.

(ii) Pulmonary vein ablation catheters (PVAC) - he pioneered clinical work on ‘single-shot’ PVACs and is senior author on the first report (American College of Cardiology, New Orleans, 03.2007); the technology has been used to treat >60,000 patients and now provides the platform for electroporation-based pulsed field ablation recently trialled (01.2021).

(iii) Atrial-selective ion channel modulators - As Principal Scientific Advisor (2002-2016) to Cambridge-based VC- and Wellcome-backed Xention Ltd he played a leading role in developing atrial-selective Kv1.5 modulators shown to be effective in AF suppression in phase II clinical trials providing a template for the design of such trials.

(iv) Voltage-based cardiac mapping - Validated by his model-based work, he developed and then completed clinical trials of now patented (US 10,601,119) voltage-based activation mapping. The demonstration of capabilities in predicting VF occurrence refined ICD implant decisions and also prompts a re-evaluation of risk management strategies.

(v) Charge Density based cardiac mapping - he has shown most recently, through application of first principles in electrostatic field theory, that calculations of charge density (CD) greatly increase single-to-noise ratios compared to voltage and permit <2 mm localisation of cardiac electrical sources. Furthermore he provided evidence for enhanced ablation efficacy through CD-determined source ablation having completed two pivotal clinical trials via international collaboration. The combined data culminated in the manufacturer (Acutus Medical) completing the ‘most successful Medtech IPO in history’. Physically differentiated CD-based phenotyping not only guides ablation (>5000 patients to date) but also enables multisite endocardial sampling; when combined with single-cell assays e.g. scRNAseq it will facilitate resolution of relationships between genetic makeup and clinical cardiac electrical function.

The last few years have witnessed substantial advances in the arrhythmia field to which Andrew has made major contributions with his input achieving clear societal benefit. He has been recognized as providing a valuable skill set traversing the wide gap between fundamental science and industrial application in a previously underserved disease domain.