ESC Paul Hugenholtz Lecture in Innovation
Innovation in pacing therapies: Where technology meets physiology
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The presenter of this year’s ESC Paul Hugenholtz Lecture in Innovation is Professor Frits Prinzen (Cardiovascular Research Institute Maastricht (CARIM) - Maastricht, Netherlands), specialist in cardiac electro-mechanics, whose highly translational work has revealed novel mechanisms, improved diagnosis and led to the development of new therapies.
What are the key themes of your lecture?
Increasing sophistication of pacemakers and their wider application across a range of cardiac disorders is the result of a combination of both technological advances and physiological exploration. On the one hand, we have made huge technological leaps in key aspects of pacemaker design and function, such as battery life and size, and leadless pacing. On the other hand, knowledge of the physiology of cardiac pacing has increased such that new clinical avenues have opened. Our work on new pacing sites provides good examples. Studies on mechanical pump function during conventional right ventricular pacing as well as in left bundle branch block (LBBB) identified discoordinate motion patterns that later became recognised as ventricular dyssynchrony. Importantly, those abnormalities were reversed by applying combined right and left ventricular pacing – biventricular pacing – which, often referred to as cardiac resynchronisation therapy (CRT), provided the first electrical therapy for heart failure (HF). After early resistance, CRT has been tremendously successful for treating selected patients with HF.
Using animal models, we also found that positioning the pacemaker electrode on the left side of the interventricular septum results in coordinate mechanics that closely mimic the physiological state.1 Since its introduction in 2017, the technique of left ventricular septal pacing (LVSP) and the related left bundle branch pacing (LBBP) have been used in millions of patients worldwide and this number is expected to rise significantly. The natural sequence when combining LVSP and LBBP – commonly referred to as left bundle branch area pacing (LBBAP) – enables other applications for which the reduced pump-function of conventional right ventricular pacing are not suitable. One example is atrial fibrillation. Historically, ‘ablate and pace’ was used only as a last resort but LBBAP is increasingly being chosen as the first approach.
What are the most important current opportunities and challenges?
Technological advances may lead us down the road to battery-free pacemakers. A self-powered intracardiac pacemaker that uses the motion of the heart to generate its own energy has recently been tested in a large animal model.2 Another exciting development is a millimetre-scale, wireless pacemaker – comprising an electrode that can be stimulated by light pulses from a wearable device – which could be used for patients requiring temporary pacing.3
A major obstacle in the progress of LBBAP is the lack of randomised comparative trials needed for full evaluation and inclusion in international guidelines. Device manufacturers are often reluctant to sponsor such trials which they perceive may bring only small benefits and yet the incremental gains for healthcare could be large.
How do you think the field will evolve in the future?
There are several new innovations in development that have the potential to extend pacing therapies even further. One of the most intriguing is in HF with preserved ejection fraction. Standard heart rate-slowing treatment increases left heart filling pressure, but computer modelling and clinical research indicate that accelerating atrial pace can effectively lower filling pressure and reduce symptoms.4 Equally exciting are the first publications about an algorithm to shorten the time between atrial and ventricular stimulation that is suggested to treat hypertension. Another area of interest is the use of brief periods of pacing post conditioning during PCI to induce cardioprotection in patients with STEMI.5 Finally, research is looking at combining a leadless pacemaker with a subcutaneous implantable cardioverter defibrillator to provide the full spectrum of anti-arrhythmia therapies without leads.
If we know where we want to go, I believe that developments in technology and physiology knowledge will help us to get there.
References
- Peschar M, et al. J Am Coll Cardiol. 2003;41:1218–1226.
- Liu Z, et al. Nat Commun. 2024;15:507.
- Zhang Y, et al. Nature. 2025;640:77–86.
- van Loon T, et al. Eur Heart J. 2024;45:4953–4964.
- Waltenberger J, et al. JACC Cardiovasc Imaging. 2014;7:620–626.
