Acute allograft rejection (ACR) is an important cause of mortality and re-transplantation
in heart transplant (HT) patients, particularly during the first year. Endomyocardial
biopsy (EMB) is the "gold standard" to guide post- HT treatment. EMB is repeatedly
performed during the first year and is associated with complications that, despite
infrequent, can be potentially serious. In order to avoid the inconveniences of EMB,
non-invasive techniques have been studied to detect rejection. However, none of these
techniques has been able to replace EMB. Index of microvascular resistance (IMR) is a
specific physiological parameter to measure microvascular function. An increased index of
microvascular resistance (IMR) measured early after HT has been associated with ACR, a
higher all-cause mortality and adverse cardiac events regardless of epicardial
vasculopathy. According to available data, no study has evaluated IMR impact on post-HT
management (number of EMBs performed). The aim of this study will be to evaluate if the
use of IMR early after HT may improve the patients care after HT, by reducing the number
of EMB.
The IMR-HT study is a multicenter, prospective observational study that will include
post-HT stable patients undergoing coronary physiological assessment in the first two
months and one year. Assessment of IMR, coronary flow reserve (CFR) and fractional flow
reserve (FFR) will be performed using the standard thermodilution technique. The left
anterior descending coronary artery will be evaluated in all patients. Circumflex or
right coronary artery could be additionally evaluated at operator's discretion. An
intracoronary pressure and temperature sensor-tipped guidewire (Pressure Wire TM X guide-
wire 0.014', Abbott, IL, USA) will be used to perform the measurements. The tip pressure
sensor will be advanced into the mid-to-distal portion of the evaluated vessel. Baseline
aortic pressure (Pa) and distal intracoronary pressure (Pd) will be obtained to calculate
the resting index Pd/Pa. To measure the mean transit time (Tmn) under basal conditions,
intracoronary administration of 3 mL of room-temperature saline will be manually injected
three times in succession (3 mL/s). Then maximal hyperemia will be induced using
adenosine iv (140 to 180 mg/kg/min) and three additional intracoronary room temperature
saline boluses of 3 ml will be administered to determine the mean transit time at
hyperemia (Tmnh). Finally, fractional flow reserve (FFR), coronary flow reserve (CFR) and
IMR will be calculated using the software Coroventis Coroflow (Coroventis Abbott,
Uppsala, Sweden).
Depending on IMR values obtained in the first two months, clinical status and the other
complementary tests the physician could be able to modify the number of biopsies
established in each center protocol. If the IMR is less than 15: the number of biopsies
could be reduced or kept the same. No immunosuppressive therapy changes would be made. If
the IMR is 15 or greater: the number of biopsies would be performed as usual per
protocol, immunosuppressive therapy could be intensified or maintained the same.
Clinical conditions, laboratory findings and clinical events will be assessed at one
month and one year. Data will be included in an online database specifically designed for
the study on platform REDCap (Research Electronic Data Capture).Each center will specify
the number of annual biopsies performed based on IMR values obtained between the first
two months after HT.
A number will be assigned to each patient; their identity will not be disclosed in any
case. All shared information will be anonymized. The principal investigator at each
center will be responsible for keeping the data anonymized.Data will be processed in
accordance with the protection legislation in force (Spanish Personal Data Protection and
Guarantee of Digital Rights Act 3/2018, and Regulation (EU) 2016/679).
The study primary end point will be the number of EMB performed at one year. Other
secondary endpoints include the association between IMR and mortality, ACR, cardiac
failure, re-trasplantation and cardiac allograft vasculopathy. Patients will be followed
for up to 5 years.