Carlos A. Mestres, MD, PhD, FETCS
Clinic for Cardiac Surgery
University Hospital Zürich,
Rämistrasse 100
CH 8091 Zürich (Switzerland)
Email: Carlos.Mestres@usz.ch
Rare diseases are serious, chronic and potentialy lethal. The European
Union (EU) definition of a rare disease is one that affects fewer than 5
in 10,000 people
(1).
In the EU, these rare diseases are estimated to affect up to 8% of the
roughly 500 million population (2). In the United States, a rare disease
is defined as a condition affecting fewer than 200,000 people in the US
(3). This a definition created by Congress in the Orphan Drug Act of
1983 (4). Therefore, the estimates for the US are that 25-30 million
people are affected by a rare disease. There are more than 6000 rare
diseases and 80% are genetic disorders diagnosed during childhood.
Despite all community efforts, there are still a lack of an universal
definition of rare diseases. This was addressed a few years back by the
International Society for Pharmacoeconomic and Outcomes Research (ISPOR)
(5).
Amyloidosis is a rare disorder classified in different types. It is
registered in the National Organization for Rare Disorders (NORD)
database (6), where a report can be found addressing fundamentals for
patients, relatives and clinicians. Although classified as rare disease,
it seems that amyloidosis is increasingly being recognized as a cause of
heart failure (7). The European Society of Cardiology has promptly
recognized this in a recent position paper published by its Working
Group on Myocardial and Pericardial Disease (8). Its potential role in
heart failure with preserved ejection fraction and eventual therpeutic
approach have recently been hihglighted in some reviews (9, 10).
Having said that, Smith et al from London present in this issue of the
Journal (11) an interesting review proposal with regards cardiac
amyloidosis in non-transpant cardiac surgery. As briefly stated by the
authors, heart transplantation is becoming the ultimate therapeutic tool
in light-chain amyloidosis (AL) and transthyretin amyloidosis (ATTR),
with some interesting short-term outcomes reported in some contributions
like the recent from Vaidya et al (12). These authors report an overall
three-year survival of 81.6% in a series of 51 patients. However, this
is not, as described in their title, the focus of the authors.
With the assumption that heart transplantation works acceptably in
selected patients, an important statement in this contribution by Smith
et al (11) is that it is difficult to find a strong justificaton to
recommend a cardiac surgical intervention in patients with cardiac
amyloidosis. There are reasons to understand that these patients,
regardless of the clinical problem eventually requiring cardiac surgery,
namely aortic stenosis, mitral disease or coronary artery disease
amenable for surgical revascularization, have clear profile for intra-
and postoperative complications in the form of low output syndrom
entailing significant mortality. The pathophysiological issues
surrounding cardiac amyloidosis, meaning a restrictive physiologic with
diastolic dysfunction and substance myocardial deposition configurate a
suboptimal pattern for an extended survival.
There are still a number of issues to discuss, like ethnicity (13),
familial association, prognosis on the long-term or, even, if the
pandemic has brought additional burden to these patients (14). However,
it is not to be forgotten that this is a technically a rare disease and
collective experience, especially in the surgical field, is still
scanty. In their review, Smith et al (11) discuss a number of
small-sized studies and mortality. Most of these studies do not report
the actual cause of death. As authors discuss about potential
confounders of all these studies not knowing the actual cause of death
or, as usual, not having postmortem examinations, all goes around
confounders and speculation.
The readership should not incorporate confusing information. As per some
types of reports in the literature, it may seem that each and every
cardiac disease is amyloid-related. It is also clear that specifically
dedicated centres, like the NHS National Amyloidosis Centre in London
Amyloidosis Center, Boston University School of Medicine and others, may
have much more information as they can collect more cases and discuss
about cardiac amyloid.
After their review with focus on diagnosis, surgical risk and areas of
uncertainty that require further research, some take-home messages from
Smith et al (11) are that cardiac amyloidosis, per se , has
intrinsic poor prognosis, that surgical treatment of diseases that may
have an amyloid component like aortic stenosis need an extremely careful
and accurate infividualized assessment and that, currently, heart
transplantation has to be considered in specific subgroups. For the time
being, the indications for non-transplant cardiac surgery seem to be
restrictive. Do not forget, as stated, that rare diseases were also
called “orphan diseases”, and largely ignored due to poor economic
potential and were thus said to be ”orphaned (14). Some more time may
then be needed to understand which the role of surgery may be.