Dr Arjang Ruhparwar

Biological pacemakers and device innovation research

Dr Arjang Ruhparwar

Marie Gethins
October 2014

A well-established procedure with remarkable success rates, implantable artificial pacemakers (PMs) have been surgically inserted into humans for more than five decades. However cardiac electrophysiologists and cardiac surgeons continue to drive innovation and evolution with exciting developments in biological pacemakers, wireless PMs and rechargeable devices.

PMs are lifesaving devices for millions with abnormal or slow heart rhythms, but like most surgically implanted medical devices, they carry a small risk of infection and cannot be used in some cases, such as in small infants. For more than 12 years, research into biological pacemakers has been ongoing as a possible alternative to PMs in the future. With new animal studies continuing to produce intriguing results, biological pacemaker research is stimulating debate among top-tier cardiologists. One view is presented in this update, with another expert interviewed in the future.

Dr Arjang Ruhparwar, Professor of Cardiac Surgery at the University of Heidelberg, Germany conducted and published animal trial results on biological pacemakers more than a decade ago and follows developments with keen interest. He believes that while they are an important research area, much more work needs to be done. “Academically biological pacemakers are really interesting, but I don’t see them helping us much at this time,” he said. “The main challenge for this whole concept of biological pacing is that can we guarantee the same safety and security for patients as we already have with artificial pacemakers. That’s why I would prefer to see large cohorts of animal trials over a long period.”

In July 2014 a group at Cedars-Sinai Medical Center in Los Angeles published interesting biological pacemaker results. The group modified pigs’ hearts to mimic a fatal heart condition and then injected the hearts with an adenovirus carrying the pig gene Tbx18, which is involved in heart development. Heart cells infected with the adenovirus began expressing a variety of pacemaking genes within a day after injection and pumping the hearts at a normal rate. This was maintained for the length of the study, two weeks, approximately how long adenoviruses survive before the body’s immune system eliminates them. Dr Ruhparwar admires the study, but advises caution. “Twelve years ago we performed the first biological cardiac pacemaker test with cells. What we noticed, but did not publish, is that something – an agent or cell – can create an escape rhythm, a new rhythm and can also create arrhythmia. There is at least a theoretical risk of arrhythmia and these can be malignant if the new rhythm jumps in during the so-called vulnerable phase of the electrocardiogram (EKG/ECG) where we have a relative refractory time and where malignant arrhythmia can occur,” he said.


More research is needed to understand this potential risk as, in theory, biological pacemaker cell treatment could induce the need for an implantable cardioverter defibrillator, preventing sudden cardiac death if an arrhythmia occurs.

He also noted that there should be a very strong incentive to adopt a new technique in the face of existing highly successful and safe options. “One needs a very strong argument to use biological pacemakers – that you had no other means of treating these patients. We have other means, that may not be perfect, but at least we know what we are doing,” he said.

Considering niche applications for biological pacemakers, Dr Ruhparwar agreed there may be scope in certain indications, but highlighted ethical concerns. “I know that there was a proposal in Scandinavia about eight years ago to treat congenital AV block intrauterine in this way. If it works its fine, but as with all things, there will be casualties, there will be a learning curve. This is a very sensitive area.”

He stressed that the PM industry is continuously working on new treatment approaches and innovative device developments are emerging. Recently he has been implanting leadless PMs and is excited about the opportunity they offer to avoid scarring associated with electrodes. He anticipates that the leadless devices will decrease in size as next generation units come on the market.

Looking into the future, Dr Ruhparwar is following experiments using ultrasound instead of electricity to power PMs. Another area that has piqued his interest is rechargeable pacemakers using an external source. “I’m sure that we will see pacemakers that are rechargeable from an exterior source. I work with ventricular assist devices which consume much more energy than pacemakers and there are tests that they can be recharged with induction. I’m sure that the technology will be introduced into the pacemaker industry so we can avoid the need for device replacement. The re-chargeability of devices is going to be the next big thing in my opinion,” he said. However he highlighted that these innovations could be many years away.



Gene therapy creates biological pacemaker (2014). Available here:


Heart cells transformed into biological pacemaker (2014). Available here:


Adenylate-cyclase VI transforms ventricular cardiomyocytes into biological pacemaker cells (2010). Available here:


Biological pacemaker engineered by nonviral gene transfer in a mouse model of complete atrioventricular block (2008). Available here: