Discussion
In each of the six experiments, the system demonstrated stability across
the trial. Metabolic parameters were maintained within a physiological
range. The hearts demonstrated predominantly an aerobic metabolism
throughout the experiments as demonstrated by the neutral lactate
metabolism and the stable lactate levels across the perfusion period.
We were able to complete a comprehensive echocardiography assessment
with SAM and PAM without interfering with the operators and manipulating
the heart. This proved the effectiveness of our custom-made setup for
echocardiographic assessment during ESHP. Looking at the trend in
echocardiographic parameters throughout the trials, the expected LV
systolic dysfunction consisted of a reduction in EF, FAC, FS and RAD as
well as in GLS and GCS throughout the experiment. However, the bigger
drop was from baseline to ESHP and was partially due to cold ischemia.
During the 5.5 hours of ESHP we detected by echocardiography a slow
decrease in LV systolic function which is consistent with the metabolic
trends and while excludes heart reconditioning, given the difference of
only one hour between PAM and SAM2 towards the end of our experiment we
would assume that the heart condition would be similar. When comparing
the LV parameters at PAM and SAM2 we noticed a larger difference in load
dependent parameters such as LVEF when compared to strain. This is
likely a confirmation that the two working modes while both allowing
functional heart assessment may not be comparable due to different setup
and loading conditions.
Reliable, easy to use and reproducible methods are required to evaluate
the myocardial function during ESHP prior to transplantation. Numerous
approaches allow the assessment of organ viability during ESHP,
including biomarkers of tissue injury (i.e. lactate and troponin I),
metabolic measurements (i.e. myocardial oxygen consumption), and
hemodynamic and contractility parameters (i.e. pressure-volume loops and
echocardiography).26 In clinical practice, the heart
is preserved in a unloaded mode which does not allow for evaluation of
contractile function. The assessment of the allograft with the OCS
utilizes therefore only lactate levels and veno-arterial lactate
extraction as markers of heart viability and suitability for
transplantation.21 This is sustained by the work of
Hamed and colleagues, who found that a serum lactate level above 4.96
mmol/L was a strong predictor of graft dysfunction at 30
days,27 and has been used to identify suitable DCD
hearts for clinical transplantation.5 However, lactate
concentration only demonstrated weak to moderate correlations and
correlated with fewer outcomes compared with hemodynamic parameters.
Dornbierer26 and White10 have
reported similar findings of the limited applicability of metabolic
measurements. Biomarkers of myocardial damage like troponin I and
creatine kinase-MB have proven to be of limited value in predicting
organ viability due to their natural elevation with the warm ischemia
and preservation insult.
The evaluation of heart structure and function prior to cardiac
transplantation is therefore auspicable to better identify suitable
organs. Previous studies have suggested the advantage of contractility
measurements over metabolic parameters during ESHP, but these studies
were focused on the use of conductance catheters, which provide a broad
range of functional parameters and is the traditional gold-standard when
researching myocardial performance.12,14,18 However,
these are invasive and difficult to utilize, thereby decreasing result
reproducibility. Ideally, methods to evaluate suitable donor hearts
should be non-invasive, easy to use and quick to perform.
Two-dimensional echocardiography has also been randomly used to obtain
qualitative assessments of myocardial
contraction,22,28 however, a standardized approach to
echocardiography in the ex situ perfused heart has not been developed.
Our study demonstrates the feasibility of a complete non-invasive
quantitative echocardiographic assessment of LV systolic function during
ESHP by transitioning from LM to two different working modes. It is an
important step in facilitating a standardized non-invasive functional
assessment of the heart during ESHP to predict the suitability for
transplantation. It also provides some quantitative measurements that
may establish some references to set a benchmark for future research.