Disruptive therapies in the treatment of valvular heart disease
By Jacob Bergsland,
Founder & Chief Medical Officer, CardioMech, Oslo Norway
Dr Jacob was born in California, grew up in Norway and returned to the US to become a cardiac surgeon. During his work in Buffalo, NY, he worked as a clinical and academic surgeon and was essential in initiating cardiac transplantation and minimally invasive cardiac surgery in the city. In the 90’s he worked as a war-surgeon for the United Nations during the war in Bosnia where he established the first cardiac center in the country with local doctors. Jacob has\ worked for more than 10 years at the Intervention Center of the Oslo University Hospital, a Center for developing new methods and equipment for minimally invasive surgery and interventional therapies.
Founder & Chief Medical Officer, CardioMech
Nikolai Hiorth, Founder, CTO of CardioMech is an innovative and award winning mechanical engineer with expertise across multiple medical device and high tech domains. Nikolai co-invented DIGNUM, a CE approved device that allows patients with paralysis to live independently and is also the co-founder of CardioMech. His passion for solving challenging problems is rooted in his early days on the job site with his architect father, making countless prototypes and building extreme sports equipment, including making an electric hydrofoil, a flying surfboard.
Daniele Salamone, VP of Finance of CardioMech is an experienced strategy consultant with expertise in Corporate Development - both strategic planning and M&A transactions - and Innovation - both Start-ups and Corporate Innovation. He has direct experience in structural heart commercialization and his expertise and investor-friendly perspective will help accelerate the CardioMech program to build shareholder value. Daniele most recently worked at The Boston Consulting Group.
Rick Nehm, President and CEO of CardioMech is a seasoned medical device professional in the structural heart market with nearly 20 years of leadership experience in sales, marketing and business development across large and small companies. His expertise in product development and commercialization within interventional cardiology, cardiac surgery and structural heart will help drive the development of the CardioMech program. Rick previously held leadership roles with Boston Scientific Corp., Tendyne Holdings Inc. (Abbott) and ATS Medical (Medtronic).
As a trainee in cardiothoracic surgery in the early 1980s, I saw a busy future in cardiac surgery, focused on the classical volume procedures at that time which included coronary bypass, valve replacements, transplants and mechanical assist devices and at that time implantation of cardiac pacemakers. From a young cardiac surgeon’s point of view much had changed already. The specialty of cardiology with imaging and catheterization as focus area, made giant steps forwards, while cardiac surgical research focused on myocardial protection of the arrested heart, evaluating the clinical value of various procedures versus medical therapy and optimization and quality assessment of the “bread and butter” procedures in our specialty. Cardiac surgery had become a mature discipline, focused on production and to some extent surgeons had become adverse to change. When Andreas Gruentzig introduced balloon dilatation for coronary obstruction, most surgeons believed it would fail and to some extent it did, but stent technology provided the next great step forwards. At present percutaneous coronary interventions (PCI) is strongly dominating the invasive treatment of the coronary disease. To a large extent, surgeons did not want to or could not compete with PCI by not embracing pioneers among themselves who developed off pump bypass surgery, multiple arterial grafts and minimally invasive and robotic procedures that could potentially compete with interventional procedures. The average cardiac surgeon continued to perform most procedures through large incisions, direct vision and on the arrested heart. In general results improved and were acceptable, but the attraction and the lower morbidity of catheter-based procedures was obvious to patients and most other interested parties. Industry saw the writing on the wall early, and large investments went into research and development of new interventional procedures.
As surgeons we may have thought “at least we have the valves”, a theory that soon would be challenged by new innovations. Balloon dilatation of the mitral valve, a procedure based on early surgical procedures, had been practiced successfully for mitral stenosis, especially in developing countries. Such treatment was not used much in the West, since mitral stenosis had become less common.
Bonhoeffer did the first implantation of a biological valve in a 12 year old boy with congenital heart disease as reported in 2000. This opened up the opportunity for further catheter-based valve interventions.
Transcatheter pulmonary valve implantation
The Boenhoffer ® valve, used in the pulmonary valve
The treatment of valvular heart disease changed drastically when catheter-based therapy for aortic stenosis became a reality.
Although dilatation of cardiac valves had been performed by surgeons since the early 1900s, the difference occurred with the cardiac catheter, first used by Forsmann in 1929, and balloon dilatation by Rashkind in 1966.
The background for most of the procedures presently being performed using catheters, came from the “catheterization” of surgical procedures performed using direct vision. Few surgeons, past or present, were interested in the learning of the indirect vision methodologies necessary for the performance of catheter based therapy. The radiology and cardiology communities have therefore gradually increased their “turf” within cardiac, vascular and neurologic non-medical therapies.
While the surgical therapeutic space for aortic valve disease is rapidly being eroded, due to the excellent results demonstrated from TAVI-therapy, treatment of mitral regurgitation is under-going transformation due to various potentially disruptive therapies.
Not surprisingly most of the disruptive catheter-based treatments are based on validated surgical methods performed with open or in some cases thoracoscopic- and robotic- operations.
Transcatheter aortic valve implantation (TAVI)
The Sapien® valve used to treat aortic stenosis
Invention of the cardiopulmonary bypass machine opened up the opportunities for treatment of almost all cardiac conditions in all age groups. Operations were performed with direct surgical vision, augmented by magnifying glasses in most cases. Cardiac catheterization was used for diagnosis together without ultrasound and x-ray examination. Miniaturization of catheters and devices and improvements in imaging techniques has made it possible to perform an increasing number of procedures without direct vision. Several congenital conditions can now be treated by the use of catheters and in adult patients both coronary artery and valvular disease are increasingly being treated by catheter-based technology. Similarly, the surgical discipline of vascular surgery, has more or less been eliminated in its traditional sense, both for central and peripheral conditions.
New technology is causing disruptive changes within most medical specialties, including in cardiovascular disease. This requires organizational changes in all aspects of medical care, maybe especially within the education of medical specialists. The development of functioning heart teams consisting of cardiologists, surgeons and imaging specialists will make it possible for patients to get full benefits of the technological revolution presently in progress.
Please Note: Some of the products described in this article are in various stages of development and are not approved for clinical use.
All authors are shareholders and hold positions in Cardiomech AS. A Norwegian and US based medical technology company.
Conflict of interest
Percutaneous annuloplasty: Two groups have developed devices for construction of an annuloplasty through a transseptal approach.
Cardioband® is a flexible annuloplasty device where the ring or strip is sutured in place with screws and the band tightened. The procedure is performed with echocardiographic and fluoroscopic vision.
Millipede® is a full annuloplasty ring, secured with screws. The distance between screws can be individually adjusted, theoretically making local and accurate adjustment.
Cardioband ® Used for percutaneous annuloplasty
Millipede® Used for percutaneous annuloplasty
Chordal repair: Several devices have been developed for implantation of artificial chords to support flailing or prolapsing valve segments. NeoChord® and Harpoon® use a transapical approach through a small thoracotomy, while Chordart has developed a transseptal method as has Cardiomech® who has developed an anchor based adjustable repair using PTFE.
NeoChord ® Transapical implantation of neochords
Cardiomech ® Percutanous implantation of neochords
Coronary sinus interventions:The coronary sinus runs along the posterior mitral annulus, and by placing anchors in the distal and proximal part of the sinus, annuloplasty can be performed.
Carrilon ® Used for coronary sinus based annuloplasty
Alfieri repair: Transseptal “Alfieri” repair with Mitraclip® The Mitraclip device is presently on the market and has been used successfully to treat both degenerative- and functional- regurgitation. The device fixes the two leaflets to each other, thereby creating a catheter-based fusion of the leaflets. The device has been demonstrated to reduce mitral regurgitation and improve quality of life in randomized studies. The Pascal ® device also produces an Alfieri type repair
Mitraspacer ® uses an interesting approach to reduce or eliminate regurgitation. A balloon is placed in the center of the valve eliminating the non-coaptional space.
Mitraclip ® Percutanous Alfieri Repair
Mitral stenosis: Balloon valvuloplasty remains an effective treatment for mitral stenosis and although it has higher recurrence rates than surgical therapy, the treatment is recommended especially for early cases in low income countries.
Mitral regurgitation (MR): MR represents the most common disease of the mitral valve in western countries and is therefore very important from the medical community’s and patients’ point of view. It affects all ages and comes in several forms, and we separate between degenerative- and functional- regurgitation. Degenerative regurgitation is due to abnormalities in the valvular system such as ruptured chords, so called floppy valves and others. Functional regurgitation is usually due to disease of the left ventricle, dilatation of the annulus or long-standing degenerative regurgitation.
Surgical repair of the mitral valve includes resection of a prolapsing leaflet, implantation of artificial chords and usually an annuloplasty ring to prevent or reverse dilatation. Surgical mitral valve repair for degenerative disease in expert hands have excellent results and almost 0% mortality. Surgery for functional disease has much worse results and survival depends on the degree of ventricular dysfunction.
Interventional therapies for mitral valve regurgitation: The mitral valve is anatomically and functionally much more complicated than the aortic which is essentially passive, while mitral valve function is also dependent on the leaflets, but in addition on the sub-valvular apparatus including the papillary muscles. Although mitral stenosis can be treated with balloon dilatation, regurgitation requires more complex therapies similar to what is seen in surgery. A number of approaches has been developed and attempted, based upon correction of various anatomic and physiologic defects. In the following a few of the approaches to catheter-based intervention for mitral valve regurgitation. The reader is advised that most of the devices mentioned here are in various phases of pre-clinical or clinic- testing and evaluation.
Transcatheter mitral valve procedures
Balloon dilatation of mitral stenosis