Safety and feasibility of adenosine stress cardiac MRI in heart transplant recipients

Stress cardiac magnetic resonance (CMR) perfusion imaging is recommended in international guidelines as a class I indication in patients with known or suspected coronary artery disease,1 and it is a promising non-invasive technique for the detection of cardiac allograft vasculopathy (CAV) in heart transplant (HT) recipients.2,3 However, there are concerns regarding the use of adenosine as a vasodilator stress agent after heart transplantation due to increased susceptibility of the atrioventricular node of the denervated heart to exogenous adenosine.4–6 Regadenoson (a selective A2A adenosine receptor agonist) has proved safe in stress CMR after HT7 but there are sparse safety data on the use of adenosine CMR in this setting. Accordingly, we aimed to assess the safety and feasibility of adenosine stress CMR perfusion in orthotopic HT recipients with suspected CAV. This retrospective study received the approval of our local institutional review board. We analysed the incidence of adverse effects of adenosine stress CMR, systematically documented in our workflow, among orthotopic HT recipients undergoing clinically indicated stress perfusion CMR for suspected CAV between 2015 and 2023 at Harefield Hospital in the UK. Baseline CAV was assessed on either invasive or computed tomography coronary angiography based on the 2010 standardized nomenclature of the International Society for Heart and Lung Transplantation8 and accordingly classified based on the presence of moderate–severe (CAV2–3) vs. non-significant or mild (CAV0–1) vasculopathy. For each CMR study, changes in heart rate and blood pressure at baseline, stress, and rest were noted, along with any symptoms and the presence and extent of inducible myocardial ischaemia both on first-pass perfusion and perfusion mapping (quantitative perfusion). Stress adequacy was assessed based on patient symptoms and haemodynamic response. Indices of rest myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) were derived by standardization of absolute parameters to the rate-pressure product (resting heart rate [bpm] · systolic blood pressure at baseline [mmHg]/1000), to account for variability in haemodynamic conditions.9 Seventy adenosine stress CMR studies performed in 60 individual patients were identified (31.7% females) at a median of 18.3 years after transplantation (IQR 3.1–23.9); 13.3% of studies were conducted within the first year, and 25.0% within three years after HT. The mean (SD) left ventricular ejection fraction was 61.7% (12.5%), with seven patients (11.7%) having an ejection fraction < 45%. N = 37 (61.6%) patients received adenosine at standard dose (140 μg/kg/min), while n = 23 received a higher dose (180 or 210 μg/kg/min). During adenosine infusion, the haemodynamic response was highly variable (Figure 1A): heart rate increased from a mean ± SD of 82 ± 14 to 91 ± 18 beats per minute, while systolic blood pressure decreased from 132 ± 16 to 124 ± 14 mmHg. Overall, 50.1% of patients reported chest tightness or chest pain during infusion, 22.4% reported shortness of breath, 17.2% did not experience any symptoms, and 10.3% had hot flushes. No life-threatening adverse events, no brief or prolonged atrioventricular block, and no major arrhythmia occurred during or immediately after adenosine infusion, with one patient having self-limiting sinus pauses (Table 1). Mild, transient adverse effects were registered: three patients (4.5%) complained of headache, and another reported nausea. Significant myocardial ischaemia was reported in 18.3% of studies. At logistic regression, stress MBF (P = 0.043), rest MBF index (P = 0.019), and MPR index (P = 0.009) were found to discriminate patients with moderate–severe CAV from those without significant CAV (Figure 1B). Inducible ischaemia on visual assessment (P = 0.35) and the ischaemic burden (% of ischaemic LV myocardium, P = 0.16) did not identify patients with CAV. Panel A shows haemodynamic changes elicited by adenosine infusion. Panel B shows stress MBF and MPR index in patients with no or mild CAV compared with patients with moderate–severe CAV. BP, blood pressure; CAV, cardiac allograft vasculopathy; MBF, myocardial blood flow; MPR, myocardial perfusion reserve. MPR index was obtained by adjustment to the rate-pressure product (resting heart rate [bpm] · systolic blood pressure at baseline [mmHg]/1000). P-values refer to logistic regression models. Symptoms during adenosine infusion and adverse events causing adenosine stress perfusion CMR scan interruption among patients with orthotopic cardiac transplantation Symptoms and adverse events are systematically collected by the CMR reporting clinical staff using an ad hoc form. In our study, we observed standard- and high-dose adenosine stress perfusion CMR to be safe and feasible in a substantial cohort of HT recipients (with 25% stressed within 3 years of transplantation), and able to elicit adequate cardiovascular and symptomatic responses in patients. This study adds to the existing body of literature on stress CMR10 by demonstrating this pharmacological test’s safety and feasibility profile in heart transplant recipients. MBF and MPR index, easily measured inline during the scan, represent promising markers of significant CAV with plausible incremental value over this population’s qualitative assessment of stress-inducible ischaemia. Patients with HT typically undergo regular invasive angiography studies as part of their clinical follow-up. The potential to identify an alternative, accurate non-invasive test for the detection of CAV is attractive both for the patients and for healthcare systems, given that a non-invasive, radiation-free test is both safer and cheaper. Given the high morbidity and mortality associated with CAV and the low yield demonstrated by qualitative approaches to ischaemia in these patients,11 evaluation of myocardial perfusion with quantitative CMR methods has the potential to significantly improve the utility of CMR after heart transplant, which is currently well-established for graft rejection surveillance, less so for CAV. The diagnostic accuracy, prognostic yield, and overall clinical value of quantitative perfusion stress CMR in HT recipients should be evaluated in future studies. None. The data underlying this article will be shared on reasonable request to the corresponding author.