Volume 68, Issue 2 Louisville Medicine | Page 23

catheter to perform a balloon valvuloplasty of the pulmonic valve. 6 The development of balloon angioplasty of coronary arteries helped to drive interest and technological advancements in dedicated balloon catheters for valvular heart disease. Dr. Jean Kan at Johns Hopkins University further refined the technique and equipment, first using an animal model and then in humans starting in 1982. 7 The success of pulmonary valvuloplasty lead to interest in treating mitral and aortic stenosis. Expanding catheter-based therapies to other valves proved more challenging as there was not a direct antegrade route to the valve, as there is with the pulmonary valve. For this reason, the first balloon valvuloplasty performed by Kanji Inoue were done via an open surgical approach in 1984. Given the success of the procedure to address rheumatic mitral stenosis, James Lock adapted the procedure and accessed the left atrium and mitral valve via a transeptal puncture, to perform the first percutaneous mitral valve commissurotomy that same year. 8 This approach is now considered the preferred initial approach to address rheumatic mitral stenosis by delaying the need for valve replacement in younger individuals in the hope to avoid multiple surgeries. Use of valvuloplasty balloons in the aortic position to treat aortic stenosis came soon after. Alain Cribier at Charles Nicole University in France performed the first balloon aortic valvuloplasty in 1985. 9 Although there was initial improvement in patients after valvuloplasty, the durability of the results was only temporary. This approach did not provide a long-term treatment option for patients who were not surgical candidates. The procedure did help provide a bridge to surgery for patients who may at first not be good surgical candidates due to acute decompensated heart failure or other confounding issues. As a result, balloon aortic valvuloplasty is still in use today for this purpose. Given the early re-stenosis that occurred with balloon aortic valvuloplasty, the search for a more durable therapy continued. The first transcatheter valve was developed by Dr. Andersen and consisted of an intact porcine valve which was sutured to a wire frame that could be crimped onto a balloon. Although using a similar design to current transcatheter valves, this first-generation valve was very large at approximately 41 F in diameter and required the use of a midline laparotomy to access the abdominal aorta to insert the valve. Early studies in a pig model demonstrated success in treating the stenosis. However, due to the valve’s large size, coronary artery obstruction was also frequent, so this was never expanded to humans. 10 Fortunately, Cribier continued his research into a catheter-based valve. His group was able to refine the idea of a “stented valve” by implanting Palmaz stents into the aortic valve of human cadavers. He was able to demonstrate that the stent strut effectively opened the valve in a circular manner allowing for valve leaflets to function inside similar to bioprosthetic surgical valves. These studies also helped determine appropriate sizing of the valve to prevent coronary obstruction. 11 Initial attempts to get industry to help with developing the technology were unsuccessful, with no company showing any interest due to concerns about potential complications from a non-surgical valve. After being told by one executive that his valve concept was “the most stupid” idea, this finally prompted Cribier and other leaders in interventional cardiology to form their own company Percutaneous Valve Technologies (PVT) to engineer and design the first models of Cribier valves. These have served as the foundation for the current balloon expandable valves used today. Based on the successful implantation of his valve in sheep, 12 the valve was approved for compassionate use in humans with the first TAVR implanted in a human on April 16, 2002. 13 Based on the success of the early “feasibility” of human trials, PVT was bought by Edwards Lifesciences in 2004, which allowed for more rapid development of valve design and delivery system. This same year, Medtronic also began developing its own valve platform that consisted of a self-expanding valve which could also address aortic stenosis. With the industry now interested in catheter-based valves, enrollment in the PARTNER trial began in 2007. This trial randomized inoperable patients to TAVR versus medical therapy and high-risk surgical patient to TAVR versus SAVR. The results demonstrated clear benefit in the inoperable group receiving TAVR and noninferiority of TAVR compared to SAVR, prompting FDA approval in 2012. 14 Further comparison trials in intermediate-risk patients 15,16 were able to demonstrate similar noninferiority of TAVR to SAVR, which led to commercial approval for TAVR in intermediate-risk patients in 2016. Commercial approval for TAVR in lowrisk patients occurred in 2019 based on the PARTNER III Trial. 17 After just 18 years of use of transcatheter valves in humans, the future of TAVR in some ways is already in practice. What started out as a treatment option for inoperable or high-risk patients has now expanded to a treatment option that is comparable to surgery. Now as the multi-disciplinary heart team meets to discuss treatment options for patients, both TAVR and SAVR are considered, allowing more patients to be appropriately treated as well as receive the best-tailored treatment option. Just like techniques and technology for valvuloplasty were expanded from the pulmonic to mitral to aortic, balloon expandable TAVR valve are now being used to replace pulmonary 18 and mitral valves. 19 The history of this rapidly developing technology has demonstrated that we are likely only at the early stages of the transcatheter valve innovation. More is yet to come. References: GETTING TO THE HEART OF MEDICINE 1 Osnabrugge RL, et al. Aortic stenosis in the elderly: disease prevalence and number of candidates for transcatheter aortic valve replacement: a meta-analysis (continued on page 22) JULY 2020 21