The number of people living beyond 80 years is expected to quadruple in the next five decades and, as a result, the medical community can expect to see a corresponding increase in patients with degenerative heart valve disease, along with a rising demand for new therapeutic choices. 

Severe aortic stenosis is the most common cause of symptomatic valve disease in elderly people; the prevalence of at least moderate aortic stenosis in the general population more than triples from 2.5% at age 75 to 8.1% at age 85.¹

Without interventional treatment, symptomatic patients with severe aortic valve stenosis have a dismal prognosis. Patients who do not undergo aortic valve replacement (AVR) have no effective, long-term treatment option to prevent or delay their disease progression; studies indicate that survival after onset of symptoms is 50% at two years, and only 20% at five years.² However, a significant proportion of high-risk patients are denied surgical AVR because of age and comorbidities. The Euro Heart Survey on valvular heart disease revealed a reluctance to refer elderly patients for this surgery, with a decision not to operate taken in approximately one-third of severe cases due to the perceived risk.³

Against these changes in demographics and the emerging role for less invasive alternatives, new procedures, such as transcatheter aortic valve implantation (TAVI), are proving increasingly attractive in patients with high risk or even contraindications for surgery.⁴ TAVI, or percutaneous aortic valve replacement (PAVR), is an innovative and high-tech alternative to open-heart surgery in which a compressed tissue heart valve is placed on the balloon catheter and is positioned directly inside the diseased valve. The balloon is then inflated to secure the replacement valve in position.

There are currently two major catheter-based approaches to the aortic valve: the transfemoral approach, in which the catheter is placed in the femoral artery (in the groin) and guided to into the heart chambers; and the transapical approach, in which a small incision is made between the ribs and the catheter is inserted into the apex of the left ventricle and positioned directly inside the diseased aortic valve.

The procedure is performed on the beating heart and does not require cardio-pulmonary bypass. A multidisciplinary approach is essential, involving interventional cardiology and cardiothoracic surgery in a ‘hybrid’ operating environment with advanced imaging capabilities. 

Emergence of TAVI technology

Before the introduction of TAVI, patients considered at high risk for surgical treatment were managed with medical therapy or with balloon aortic valvuloplasty, both of which had poor overall survival benefit. Although researchers had been experimenting with the concept of transcatheter heart valve implantation since the 1970s, 20 years later the case for TAVI appeared unrealistic. That is until, at the end of the 1990s, German cardiologist Prof Philipp Bonhoeffer developed a new technique to replace a heart valve without the need for surgery. The procedure was based on the concept that a heart valve sewn inside a stent could be reduced in size, by crimping it onto a balloon catheter, and then introduced through a peripheral vessel to the desired implantation site in the heart, where inflation of the balloon would deploy the valved stent within the old dysfunctional valve.⁵

In 2000, Prof Bonhoeffer described the first percutaneous valve implantation in a right ventricle to pulmonary artery conduit in a 12-year-old boy with stenosis.⁶ Soon after, French cardiologist Dr Alain Cribier performed the first clinical antegrade transcatheter placement of an aortic valve in a 57-year-old man with calcific aortic stenosis.⁷

This marked a revolutionary, minimally invasive way of treating aortic stenosis in patients at high risk for conventional surgery. In subsequent years, a significant learning curve involving safety and efficacy improvements led to several modifications of first-generation percutaneous heart valves, with TAVI achieving Conformité Européenne (CE) mark approval in 2007.

Hundreds of patients in Europe were included in post-marketing registries conducted with the two valve delivery systems available at the time – the Medtronic CoreValve and Edwards Sapien valves. These registries led to improvements in patient screening, technical modalities and greater prevention and management of complications. As a result, excellent haemodynamic results were increasingly recorded, which compared favourably with traditional surgical AVR, as well as lasting functional improvement and better patient survival. 

In 2011, a mortality rate of 6-10% at one month and a one-year survival rate of 80% after transfemoral TAVI were reported in the SOURCE registry.⁸

Limitations to these current-generation devices were also identified, with regard to control and accuracy in positioning and placement, potentially increasing the risk of paravalvular leak and the need for the implantation of a permanent pacemaker after the procedure. The most significant complications include vascular damage, stroke, paravalvular aortic insufficiency and heart block.

A milestone in the acceptance of TAVI as a viable alternative to conventional treatment came with the PARTNER trial results. Involving more than 1,000 high-risk patients in the US, this was the first randomised controlled trial to demonstrate that TAVI in non-operable patients is highly superior to standard therapy (with an absolute increase in survival of 20%), and is not inferior to AVR in high-surgical-risk patients, in terms of all-cause mortality at one year. 

The follow-up PARTNER 2 study also demonstrated comparable mortality and durability after transcatheter and surgical AVR at two years in high-risk surgical candidates with severe aortic stenosis. Although nearly twice as many strokes occurred in the TAVI group compared with the surgical AVR group at 30 days, the frequency of strokes was similar at two years, suggesting that TAVI did not increase late stroke risk.⁹

These findings contributed to the approval of TAVI for non-surgical candidates by the US FDA in November 2011, and in high-surgical-risk patients in October 2012. The procedure is now approved in more than 50 countries and has been performed on more than 80,000 patients worldwide.

Since its commercialisation in 2007, the number of TAVI procedures has grown exponentially in Europe, and the number of TAVI centres has increased ninefold from 37 to 342 in 2011. 

The first TAVI procedure in Ireland was performed in the Blackrock Clinic in 2008. However, only after lengthy negotiations with health insurers could the clinic introduce TAVI as a service covered by certain insurance policies (dependent on patient plan). This happened in late 2011. Other TAVI centres in Ireland include the Mater Private and Beacon Hospitals. Across the border, in the Royal Victoria Hospital, Belfast, Dr Ganesh Manoharan, a consultant cardiologist, is the clinical lead for the TAVI programme in Northern Ireland and functions as a clinical proctor for the Medtronic CoreValve and the St Jude Medical Portico TAVR programmes. The new and innovative Portico heart valve is the only approved transcatheter valve that can be completely resheathed, repositioned at the implant site or retrieved before it is released from the delivery system. 

Dr Manoharan, who led a major trial for the device, recently presented first-in-human 12-month data demonstrating the safety and efficacy of the Portico transcatheter heart valve at the 24th annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium. In the study, there were no vascular complications, major strokes or deaths among study patients and no new pacemakers required (some of the complications associated with TAVI). Clinical improvements that were noted at earlier follow-up intervals were sustained out to 12 months (including valve function).

“We have used two different types of valves for this but in both there were problems if we weren’t happy about the location of the valve,” Dr Manoharan said in an interview with the Belfast Telegraph. “With one of them, if we weren’t happy about the position of the valve we had to start all over again with a new valve, which means the procedure becomes more complex. However, with the portico transcatheter valve, we can move it around until we are entirely happy with its position.

“We were the first centre in the world to carry out the first human-based trial with this device, because of our expertise in carrying out this procedure. During the trial the device was fitted in 10 patients and the results were very encouraging, with all patients doing very well. The valve is proving to truly be a next-generation technology. It really is phenomenal and has produced some very exciting results.”

St Jude Medical’s 23mm Portico transcatheter aortic heart valve and transfemoral delivery system received CE mark approval in November 2012.

Adoption rates for the procedure have shown marked variety across Europe. An investigation of TAVI procedures across 11 European countries found that more than 34,000 patients underwent TAVI from 2007-2011. The research identified a wide variation in the number of TAVI implants per million of population with estimates in individual countries ranging from 10 in Ireland to 89 in Germany. 

In 2011, the highest annual increase in procedural volume was observed in France (61%) and Germany (49%), while Ireland (-15%) and Portugal (-3%) experienced a decline.¹⁰

In Ireland, a review of 56 patients who underwent a TAVI procedure found that the overall mortality within 30 days was 10.7%, which is in line with international findings (5.4-11.3%). In contrast to other studies, there were fewer post-procedural complications.¹¹

“The findings identified that the major outcomes were similar to international practice and were superior to standard therapy, indicating few clinical barriers to the implementation of this procedure in the Irish setting,” said study author Sinead Teehan, CNS interventional cardiology, St James’s Hospital.

The TAVI procedure has a success rate of 90-95%. However, as with any heart surgery, there are risks attached. New technology advances promise to simplify TAVI and to improve the results by reducing the rate of complications, such as paravalvular aortic regurgitation, annular rupture and conduction disturbances, which may impact on the clinical outcome. As these weaknesses are overcome, it is possible that patients at lower risk might benefit from TAVI in the near future. 

References

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