There is new hope for elderly patients but the treatment raises the issue of the therapeutic futility.

For the elderly who suffer from shortness of breath, chest pain or fainting spells, the underlying cause of the symptoms may not always be blockage of the heart arteries but may be due to disease of heart valves.

When the left lower chamber of the heart contracts, blood is pumped out of the heart through the aortic valve which then opens to allow blood to flow into the aorta which is the main arterial vessel providing blood supply to the entire body.

Subsequently, the left lower heart chamber relaxes and the aortic valve closes, preventing blood in the aorta from flowing backwards into the heart chambers.

With increasing longevity, degeneration of the aortic valve becomes increasingly common.  Over time, the aortic valve thickens and often becomes calcified, thereby reducing the size of the valve opening and hence restricting the amount of blood that can be pumped out of the heart.

This condition is termed aortic stenosis. When the opening of the aortic valve becomes critically small, it can potentially lead to death.

Logically, it would seem that replacing the degenerated aortic valve with a new one will solve the problem. However, as many of these patients are much older and often have other serious medical problems, the risk of surgical valve replacement can be high.

Those deemed to be at high-risk or are too sick for surgery are referred for palliative care. Once the patient has shortness of breath, chest pain or fainting spells resulting from severe aortic stenosis, the average survival will be short.

Transcatheter Aortic Valve Replacement (TAVR)

However, there is now new hope for this group of patients. Years of medical research has led to the development of less invasive techniques to treat severe aortic stenosis.

Increasingly, the technique of inserting an artificial aortic valve through an artery, bringing it up the aorta, inserting the artificial valve into the site of the native aortic valve and deploying it to replace the function of the original valve is being used. This procedure is called Transcatheter Aortic Valve Replacement (TAVR).

Medication versus TAVR

The five-year results of the prospective randomised Placement of Aortic Transcatheter Valve (PARTNER) Trial were published in March 2015 in the highly regarded LANCET journal. This segment of the study compared standard medical treatment versus TAVR.

For patients with severe inoperable aortic stenosis who remained on medical therapy, the median survival was less than one year. At the end of five years, only six patients in the standard medical therapy group were still alive and of these six, five had undergone surgical aortic valve replacement.  Simply put, almost every person who remained on medical therapy died within five years.

For every 100 patients with inoperable severe aortic stenosis on medical treatment only, the death rate at one month, one year and five years was about 3 per cent, 51 per cent and almost 100per cent, respectively.

For every 100 of these patients who undergo TAVR, the death rate at one month, one year and five years was 5 per cent, 31 per cent and 72 per cent, respectively. For this group of inoperable aortic stenosis patients, death is not inevitable and TAVR provides them with a ray of hope.

Comparing TAVR with surgery

In the other segment of the PARTNER study, a group of operable but high-risk surgical patients with severe aortic stenosis was randomised into a group undergoing TAVR and another undergoing surgical replacement of valve. At the end of five years, about two-thirds of the patients had died and about half of the patients died of heart disease, with no significant difference in death rates between those who underwent TAVR and those had surgery.

There was also no significant difference in the rates of major complications including stroke (about one in eight), heart attack, and kidney failure.

A meta-analysis of data from 17 studies on TAVR showed for every 100 patients, within the first 30 days after TAVR, there were about eight deaths, three strokes, 12 major vascular complications, 22 major bleeding episodes  (of which about 16 were  life-threatening bleeding) and one per cent heart attacks.

Heart electrical abnormalities requiring the insertion of a permanent pacemaker varied from 4.9 per cent to 29 per cent depending on the type of valve used.

Assessing the risk

Although the PARTNER study showed that at the end of five years, TAVR was superior to medical therapy and was equivalent to surgical replacement of the aortic valves, nevertheless, the data also showed that many patients died soon after TAVR or had little improvement in quality of life or functional status after TAVR.

At the end of five years, the death rate for the inoperable patients who underwent TAVR (72 per cent) and the death rate for the operable but high surgical risk group who underwent TAVR (68 per cent) were both high.

A recent review in the Circulation journal on TAVR raised the issue of therapeutic futility. In the review, therapeutic futility was defined as “lack of therapeutic efficacy, especially when the therapy is unlikely to produce the desired clinical result, as judged by a group of competent physicians, or lack of meaningful survival as judged according to the personal values of the patient”.

Current risk assessment guides do not provide a holistic assessment that an experienced surgeon will consider before performing any surgical procedure, taking into account factors such as malnutrition, cachexia, kidney failure, poor physical condition, whether the patient is bed-bound or wheelchair-bound, presence of cancer, dementia, previous disabling stroke, and other debilitating conditions that prevent the patient from having a reasonable functional status even after successful TAVR. Studies have shown that those who are frail have poor outcomes after TAVR and the current risk assessment does not take this into account.

To do or not to do

While TAVR provides a better outcome for inoperable aortic stenosis patients compared to inevitable death, nevertheless, the large majority of these patients who undergo TAVR die within five years. Part of the reason is that the mean age of the patients in the study is more than 80 years.

The procedure is costly and carries a high risk of complications, hence a thorough discussion with the doctor is necessary to avoid therapeutic futility.

To maximise the success of TAVR and to avoid therapeutic futility, a few points should be considered:

1. The procedure requires highly trained doctors to minimise the risk of complications and high operator volume and experience are important considerations in minimising complications.

2. Patient selection is important and it is important to identify those who are not likely to benefit functionally from TAVR. A holistic risk assessment should be made to consider the quality of life and likely functional status post-TAVR. Those with disabling stroke, poor heart status or chronic kidney impairment are likely to have a poor outcome after TAVR and hence may not benefit from TAVR.

3. As 50 per cent of the deaths after TAVR are due to heart disease, a proper assessment and optimisation of the heart status pre-TAVR may help to reduce deaths post-TAVR.

4. Some complications are more frequent with certain types of valves, and hence the incidence and potential complications associated the choice of valve used should be understood.

These are early years for TAVR and the devices are still evolving to minimise the complications post-TAVR.  Over time and with more research data, better patient selection and improvements in devices, it is expected that TAVR should produce better outcomes.