Disruptive technologies in cardiac surgery and interventional cardiology

: The last several decades have witnessed a huge expansion of surgical and interventional treatment of cardiac disease. Axel Cappelen from Oslo, Norway was one of the first to operate on the heart, something that had until then, been considered foolish and without chance of success [1]. Cappelen dared to operate on the heart in spite of Billroth's stark warning against such "unwise" at-tempts as he ligated a bleeding coronary artery caused by a stabbing injury. Most of the innovation in recent years has been within the interventional cardiology domain in contrast to the first 7 decades of the 20th century, when surgeons dominated. Cardiac surgeons have developed less invasive procedures, although the most common surgical incision is based on the time-honoured and large median sternotomy incision. Many surgeons continue to prefer the concept of "Grosse Chi-rurgen, Grosse Schnitte" and have stayed away from minimisation and continue to use direct vi-sion, usually augmented by magnification glasses, median sternotomy and cardiopulmonary bypass (CPB). However, new technology has made the need for CPB less important [2]. In this article a selection of recently developed devices for cardiac intervention will be described.


INTRODUCTION
The development of cardiac interventional care has required technological innovation and dedicated and qualified personnel. It was more than 100 years ago that the first coronary bypass procedure was performed on research animals by the Nobel Laureate Alexis Carrell, but it required the development of cardiac catheterisation to diagnose the extent and localisation of coronary lesions and the CPB-machine to operate on a motionless heart. The heart-lung machine made coronary bypass feasible, but again became unnecessary with the development of off the pump bypass surgery (OPCAB). New technology made OPCAB feasible and safe [3][4] [5].
Interestingly, many of the common cardiac conditions affecting the heart valves had surgical solutions before CPB was developed and some of these methods have now been revived using catheter-based techniques. Mitral stenosis, one of the most common cardiac conditions before the time of antibiotics and treatment of streptococcal infections, could be effectively relieved with mitral commissurotomy performed with a left thoracotomy and access to the mitral valve through the left atrial appendix. The surgeon would use his finger or an instrument to dilate the stenosed valve, thereby relieving disabling congestive heart failure ( Figure 1) [6]. In the Western World such closed procedures were mostly replaced by open commissurotomy on CPB and an arrested heart to decrease the risk of embolisation. Later, catheter-based balloondilatation, using a transseptal catheter technique, has become a successful method for treating mitral stenosis (  In 2003 it was reported that a third of patients with mitral stenosis were treated with balloon dilatation in Europe [8]. Closed, operative dilatation for aortic stenosis without CPB was performed through a transapical technique and a surgical instrument was used to open up the fused aortic leaflets. This procedure was less successful than dilatation of the mitral valve as demonstrated by the experience with aortic balloon valvuloplasty [9]. For many years valve replacement was the most common invasive treatment for patients with disease of the valves, regardless of whether the pathology caused stenosis, insufficiency or a combination of both. Both tissue and mechanical valves performed well and selection of type depended on age, co-morbidities, surgeon and patient preferences or other factors [10]. The pulmonary and tricuspid valves were treated surgically and to an extent with catheter-based techniques. Focus of development, science and practice in the early, mainly surgical, era was valve-replacement and a number of mechanical valves were developed, including Starr-Edwards, Björk-Shiley, Medtronic Hall and others. These mechanical devices were made of artificial material and required life-long anticoagulation. Alternative devices were made of a combination of biologic and synthetic tissues where the leaflets were biological and less thrombogenic. Anticoagulation could therefore be avoided, which is a major benefit for quality of life. The main disadvantage was the shorter durability of biological valves, making reoperation a common scenario especially for younger patients and pre-menopausal women.
While stenotic lesions of the mitral and aortic valves could be treated with dilatation, regurgitation was a more complex issue. While most surgeons elected to replace the leaking valves, it became increasingly evident that the degenerative valve pathology, especially for the mitral valve, could be repaired, preventing the adverse effects of a prosthesis. Surgical mitral valve repair became, and still is, an excellent choice. Techniques for mitral valve repair were developed by a lifelong dedication by the French surgeon Alain Carpentier and others [11] [12]. His ground-breaking work resulted in further understanding of the mitral valve's function and pathology and the development of the techniques to repair the valve with excellent results and low rates of reoperation [13]. Aortic insufficiency has been more diffi-cult to repair and surgical therapy has mainly been the valve replacement.
Until the 1970s, cardiology interventionists were mainly involved in diagnosis of cardiac conditions, while surgery was a dominant invasive nonmedical therapy. This changed after Andreas Grüntzig's disruptive approach to coronary artery disease when he started performing percutaneous balloon angioplasty [14] [15]. After stents were added to the procedures, it has become safer and is now performed much more commonly than the coronary artery bypass grafting. To most cardiac specialists it seemed unlikely that catheter-based therapy could be a major factor in treatment of valvular conditions, except for dilatation of the mitral [16] and aortic valves [17].

THE PRESENT STATE AND EMERGING TECHNOLOGY
The development of catheter-based alternatives to surgery for stenotic lesions in coronary arteries and aortic and mitral valves led to further pursuit of new solutions by physicians, surgeons and engineers. The med tech industrial giants and numerous upstart companies saw a huge potential in developing less invasive therapies, mainly based on catheter interventions. In other surgical specialties, like gastrointestinal surgery, minimally invasive techniques have penetrated the Western world and even the remote and poor countries [18], but unfortunately thoracoscopic and robotic operations for cardiac disease has not gained general acceptance, in spite of clear demonstration of clinical feasibility and excellent results [19]. The majority of surgeons does not possess required skills or acceptance of the paradigm shifts necessary for minimal invasive approaches. However, similar to what occurred regarding valve dilatations, many new ideas for interventional therapy came from surgeons who were used to seeing cardiac pathology "in real life". When surgeons, cardiologists and engineers worked together, interventionists with imaging-and catheter-expertise could perform intracardiac procedures with good results. In the following a selection of the new devices and methods available and under development will be described. Due to space constraints, a complete review will not be possible.

Aortic valve
Dilatation of the aortic valve to relieve stenosis was attempted in the pre-cardiopulmonary bypass using a transapical approach where a surgical dilator instrument was introduced antegrade through the aortic valve. When CPB became available, aortic valves were mostly replaced using CPB and on an arrested heart. Balloon dilatation through a retrograde approach from the femoral artery continued to be a valuable technique in some cases, but the procedure either did not relieve stenosis adequately or resulted in aortic insufficiency [20]. Implantation of a prosthesis using a transcatheter approach was developed by Cribier and others, who described the procedure and initiated it clinically in Rouen, France [21]. Within a few years several implantable valves were on the market, the most common were the Sapien TM , Edwards Inc., USA and Corevalve TM Medtronic Inc., USA. Sapien TM is made of bovine tissue mounted on a cobolt-chromium metal frame and is balloon-expandable (Figure 3), while the Corevalve TM (presently named Evolut TM ) is made of porcine pericardium mounted on self-expandable nitinol ( Figure 4) [22].  Extensive, controlled, clinical studies have been undertaken demonstrating benefits compared to surgery of this transcatheter approach first in high-then in intermediate-and finally in low-risk patients [23]. In several markets transcatheter aortic valve implantation (TAVI) is now more common than surgical valve implantation. The high cost of the device and delivery catheters has been a limitation to the implementation of the technique in less prosperous markets. Several new devices are in different phases of development and will probably eventually result in a more affordable price-structure.

Mitral Valve
The mitral valve is anatomically more complex than the aortic and mitral stenosis, especially when less calcified, can usually be successfully treated with balloon dilatation [24]. Mitral regurgitation (MR) is more difficult to treat as it has a number of different aetiologies and variable anatomy, but development has accelerated in spite of technological challenges, strict regulation and financial challenges [25].
There is much variability among regurgitant mitral valves; the two main categories being degenerative (DMR) and functional (FMR) mitral regurgitation (MR) [26]. a) Mitraclip TM , Abbott Inc., USA ( Figure 5) was designed to reproduce a surgical procedure invented by Alfieri [27]. With the Alfieri method, the anterior and posterior leaflets of the mitral valve are sutured together, creating a double outlet valve where the two leaflets support each other. Mitraclip can produce the same anatomical result as the Alfieri procedure by fixing the two leaflets together with a patented clip deployed with a catheter approach [28]. The catheter is introduced through the femoral vein and trans-septally into the left atrium. An animation can be seen on YouTube (link: https://www.youtube.com/watch?v=4-yT-P0EaZzg). Mitraclip can be used in DMR by fixing a prolapsing or flail leaflet to the opposite leaflet, thereby eliminating or decreasing MR. The device can also be used in FMR since it improves coaptation of the leaflets, thereby reducing MR. This effect on patients with FMR has been demonstrated in a well conducted randomised study in the US (COAPT-study) [29], which demonstrated lower mortality, less heart failure symptoms and improved LV function compared to the optimal medical treatment. b) Implantation of annuloplasty ring. Cardioband TM , Edwards Lifesciences, USA, is also used through a transseptal approach [30]. The annuloplasty ring is sutured in place in the mitral valve annulus, using a sophisticated anchoring system. The procedure is explained by this animation (https://www.youtube.com/ watch?v=zVlAOs3Ifsc) This ring is inspired from the surgical annuloplasty procedure and intended to reduce the size of the mitral annulus thereby improving coaptation of the leaflets. c) Implantation of new mitral chords. Several companies are working on devices that can repair the mitral valve by the placement of artificial chordae tendinae. Such procedures are based on concepts from surgical repair. MR caused by ruptured or degenerated mitral chords can be repaired by placing artificial chords between the prolapsing leaflet and the papillary muscles, thereby increasing coaptation of the anterior and posterior leaflets. Different concepts for placing such "neochords" include transapical approaches, where a small thoracotomy is used to place chords between the prolapsing leaflet and the wall of the LV. The length of the chords can be adjusted under ultrasonic imaging until MR is eliminated. DS1000 TM , NeoChord Inc., USA ( Figure 6) and Harpoon T M Edwards Lifesciences Inc, USA ( Figure 6) are devices under clinical investigations for trans-apical chordal implantation.  The device is still in preclinical trials and not available for clinical use. Several other companies are in the process of developing transfemoral devices. d) Surgical mitral valve replacement gives good long-term result for patients with MR, but can contribute to the obstruction of the aortic outlet, but this can usually be prevented by careful planning [34]. Several transapical valves have been designed and implemented including Tendyne TM , Abbott Inc., USA (Figure 8) [35] which has recently received the CE mark after successful human studies [36]. Tiara TM , Neovasc Inc., Canada [37] and Intrepid TM Medtronic, USA [38] are transcatheter mitral prosthesis in clinical trials.

Pulmonary Valve
Balloon dilatation has been used for many years for treatment of congenital pulmonary stenosis [39]. The Melody TM Medtronic, USA is a transcatheter valve designed for the treatment of leaking pulmonary valves (Figure 9), mainly used after previous surgery for congenital heart disease [40].

Tricuspid valve
Tricuspid valve disease frequently occurs secondarily to other valvular disease, which can cause right ventricular (RV) dilation and tricuspid regurgitation (TR). Surgical repair of such TR at the same time as the primary valve operation improves long-and short-term outcomes [41]. For patients who have high grade primary TR or TR after a previous valve operation, reoperation may be necessary. Alternatively, a transcatheter repair may in the foreseeable future be performed through a femoral or jugular venous approach [42]. Patients with combined disease of mitral and tricuspid valves live shorter than those with only mitral dysfunction. Several devices, some adapted from mitral applications can be used in the tricuspid area [43].

DISCUSSION
Cardiovascular disease remains the most common cause of death and disability worldwide. Surgical and interventional therapy save lives and improves quality of life for several hundred thousand patients every year. Classic open surgical operations were for decades dominating such therapy with coronary bypass and valve replacements being the most common procedures. The development of catheter-based therapy for coronary stenosis has led to a paradigm shift. CABG has become relatively less common while the use of acute and elective percutaneous coronary interventions has increased dramatically. The biggest benefit is seen in patients with acute myocardial infarction.
Interventional therapy for valvular disease is now increasing rapidly. Development of new devices ar complex and costly and requires long time for regulatory approval [44]. Use of TAVI has increased rapidly after regulatory approval of Sapien TM in 2012 [44]. A number of other TAVI valves are now on the market or under development.
The development of transcatheter devices for mitral valve repair has been slower, but the Mitraclip TM and NeoChord DS 1000 are already on the market and are expected to be followed by a number of other devices. Similarly, start up and strategic medical device companies are actively pursuing new and innovative solutions.

CONCLUSSION
In conclusion, the trend towards image-guided procedures performed with minimally invasive surgical and interventional therapies is rapidly changing the way patients with cardiovascular disease are treated. The increasing number of devices and competition in the strategic device industry will eventually bring down the costs. The availability of less invasive procedures will make effective therapies available for new patient groups, some of them not eligible for higher risk surgical operations. At the same time, shorter hospital length of stay and lower rates of adverse events will decrease cost to the individual patients and for the society at large.