Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04393181 |
| Other study ID # |
IMPROVED HEART |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
April 5, 2022 |
| Est. completion date |
April 1, 2027 |
Study information
| Verified date |
April 2022 |
| Source |
Vastra Gotaland Region |
| Contact |
Jonatan Oras, MD, PhD |
| Phone |
+46736370350 |
| Email |
jonatan.oras[@]vgregion.se |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
Severe heart failure is a diagnosis with a very poor prognosis. Heart transplantation is the
best treatment for terminal heart failure but this type of treatment is limited by the number
of available organs. About 20-25% of possible donor hearts are not considered for
transplantation because they have some form of functional impairment. The functional
impairment affecting organ donors is, however, usually reversible. A number of retrospective
studies show that cardiac function recovers and recipients of hearts with dysfunction do not
have worse outcomes compared to recipients of hearts with perfect cardiac function. However,
there are no prospective studies on whether the functional impairment of the donor heart is
of significance for the recipient. With a systematic and simple investigation of the heart,
it should be possible to identify the hearts that are safe to transplant. This will thus
increase the number of available donors.
Description:
Severe heart failure is a diagnosis with a very poor prognosis where the 2-year mortality
rate for serious heart failure is over 50%, which exceeds many cancer diagnoses. Despite
advances in pharmacological treatment and mechanical pumps, heart transplantation is
considered to be the best treatment for terminal heart failure. However, heart
transplantation as a treatment for terminal heart failure is limited by the number of
available organs. If the investigators could take care of more organs, more patients could be
transplanted. It is therefore of the utmost importance that every heart that can be
transplanted successfully is considered.
According to current recommendations, a heart should be in near perfect condition to be
considered for transplantation. For a donor heart to be transplanted, it should not exhibit:
- More than mild-to-moderate cardiac impairment (EF < 40%)
- Regional discrete wall motion abnormalities
- Need for excessive inotropic support (dobutamine >20µg/kg/minute)
- Intractable ventricular arrhythmias.
Cardiac dysfunction in organ donors, however, is usually secondary to the disease that led to
brain death and is reversible; there is nothing wrong with the heart itself but it has ended
up in an unfavorable environment that temporarily affects its function. A common cause of
cardiac dysfunction in organ donors is stress-induced cardiomyopathy/Takotsubo
cardiomyopathy. Stress-induced cardiomyopathy is a relatively newly described acute cardiac
syndrome in which the heart develops regional wall motion abnormalities caused by severe
catecholamine stimulation of the myocardium. In the organ donor, a strong catecholamine storm
is observed in combination with compression and the development of brain death, which can
trigger stress-induced cardiomyopathy. This type of change is seen in 20-25% of potential
organ donors. One of the most important characteristics of stress-induced cardiomyopathy is
its rapid recovery, however, and cardiac function is usually normalized within a few hours or
Days 8-10. This is not only seen as a functional recovery, but also a structural and
biochemical recovery of the heart. In addition to organ donors with intracranial events,
stress-induced cardiomyopathy is also seen in patients with hypoxic/anoxic brain injuries as
a result of hypoxic cardiac arrest, and even in these cases, cardiac events are temporary.
There are potentially differential diagnoses for stress-induced cardiomyopathy in potential
donors. The most important is ischemic heart disease which can quickly and relatively easily
be diagnosed with coronary angiography. Coronary angiography is performed today on
approximately one-third of potential donors and then primarily on donors with a risk profile
for coronary artery disease. Another different diagnosis is myocarditis, which does not have
the same reversibility as stress-induced cardiomyopathy and usually gives a different
echocardiographic image.
The recommendation not to utilize hearts with regional wall motion abnormalities has
inadequate scientific support. The recommendation is based on a retrospective study that is
over 30 years old and did not have cardiac dysfunction as the primary outcome measure. Upon
review of this article, the data does not support the idea that regional wall motion
abnormalities would be associated with worse outcomes. Despite this, this recommendation has
been the basis for deciding whether to transplant the heart or not. There is a wariness,
especially with American thoracic surgeons, to take into account such hearts. There is a
number of retrospective studies that show that the outcome is not worse for patients who have
been transplanted with hears that have/have had dysfunction. The main studies are presented
below:
- A study based on material from the USA (UNOS database) in which patients who received a
heart with ejection fraction <50% (n=740) were identified and compared with recipients
of hearts with normal function (n=30253). No difference in mortality at one year after
transplantation was observed between the groups.
- A study based on the same material showed that long-term survival was not inferior for
recipients of hearts with ejection fraction<50%. Cardiac function was also the same for
recipients of hearts with normal function and impaired function one year after
transplantation.
- In a study based on the same database (UNOS database) 472 recipients who received a
heart with improved function, defined as EF≤40% at one examination and EF≥50% at a
follow-up examination, were identified. The control group were recipients of hearts with
normal function EF≥55%. There was no difference in mortality, primary graft failure,
allograft vasculopathy between the groups, even when propensity score matching was
applied.
- A study based on other material from the USA (California Transplant Donor Network)
reported figures where low ejection fraction (EF<50%, number of patients not reported)
or regional hypokinesia (n=197) did not affect outcome.
- An older study based on material from the USA showed that regional hypokinesia has no
bearing on recipients' mortality. The number of patients with regional hypokinesia was
not reported but 1719 patients were included in the study.
- A study from Transplantation Centre, Sahlgrenska, analyzed donors and recipients during
a 10-year period. In total, 641 donors were included in the analyses and 155 (24%) of
the donors had cardiac dysfunction. Recipients of hearts with dysfunction (n=42) did not
have worse outcomes (death, retransplantation) compared to recipients of hearts with
normal function. Short-term outcomes (intensive care unit (ICU) care time, advanced
hemodynamic support, postoperative dialysis, rejection) also did not differ between the
groups. Cardiac function was rapidly recovered in the recipients and both groups had the
same ejection fraction already a few days after transplantation.
These retrospective studies form a relatively good foundation and cover almost 1400 patients.
However, prospective studies on transplantation of hearts with functional impairment are
missing.
At Transplantation Centre, Sahlgrenska, there are many years of experience of handling hearts
with impaired function. This clinical experience suggests that it is not associated with
complications. The studies referenced above confirm this experience.
Overall, there is room to increase the number of heart donors, and thus the number of heart
transplantations, if the heart donors with reversible dysfunction are utilized. This study
aims to prospectively investigate the cardiac function of donors and evaluate if it is of
significance to the outcome of the recipient. The study sets guidelines for investigative
procedures as well as which hearts should be transplanted, based on previous retrospective
studies. The investigators expect that the recipients' outcome will not be affected by the
cardiac function of the donor, provided the study's recommendations are followed. Our data
shows that approximately every fourth potential heart donor suffers from functional
impairment. This is in line with other studies that observed that about 20% of hearts are
refused due to affected function. The investigators estimate that a systematic consideration
of these hearts can increase the number of transplantations by 20-30%.
