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Aims  The study evaluated exercise left ventricular global longitudinal strain (LVGLS) and invasive haemodynamics for major adverse cardiac events (MACE) prediction in heart‐transplanted (HTx) patients.    Methods and results  The study comprised 74 stable consecutive HTx patients who were followed at the Department of Cardiology, Aarhus University Hospital, Denmark, from August 2013 to January 2017. All patients were transplanted a minimum of 12 months before study entry and were included at the time of their routine annual coronary angiography. A symptom‐limited haemodynamic exercise test with simultaneous echocardiographic study was performed. The primary endpoint was MACE during follow‐up defined as heart failure hospitalization, treated rejection episodes, coronary event, or cardiac death.  The median time since transplant was 5 years [1:12] and the median follow‐up was 1095 days [391;1506]. Thirty patients (41%) experienced MACE during follow‐up. Patients who suffered MACE had an impaired resting and peak exercise systolic function in form of a lower LV ejection fraction (Rest: 56 ± 12% vs. 65 ± 7%,  P  < 0.001; Peak 64 ± 13% vs. 72 ± 6%,  P  < 0.01) and LVGLS (Rest: 13 ± 4% vs. 16 ± 2%,  P  < 0.01; Peak: 15 ± 6% vs. 20 ± 4%,  P  = 0.0001) than patients without MACE episodes. In contrast, resting diastolic filling patterns were comparable between patients suffering from MACE and patients without MACE.  At rest, pulmonary capillary wedge pressure (mPCWP) and cardiac index did not predict MACE, whereas increased right atrial pressure (mRAP) was associated with increased MACE risk. Patients with peak exercise mPCWP >23 mmHg [hazard ratio (HR) 2.5, 95% confidence interval (CI): 1.2–5.4], cardiac index <5.9 L/min/m 2  (HR 2.7, 95% CI: 1.0–6.3), or mRAP >13 mmHg (HR 2.7, 95% CI: 1.1–6.3) had increased MACE risk.  Patients with exercise‐induced LVGLS increase <3.5% and peak exercise cardiac index <5.9 L/min/m 2  [HR 6.1 (95% CI: 2.2–17.1)] or mPCWP >23 mmHg [HR 6.1 (95% CI: 2.1–17.5)] or mRAP >13 mmHg [HR 7.5 (95% CI: 2.3–23.9)] had the highest MACE risk.    Conclusions  Resting haemodynamic parameters were poor MACE predictors in long‐term HTx patients. In contrast, peak exercise mPCWP, mRAP, and CI were significant MACE predictors. LVGLS both at rest and during exercise were significant MACE predictors, and the combined model with peak exercise LVGLS and peak exercise mPCWP, mRAP, and CI clearly identified high‐risk HTx patients in relation cardiovascular endpoints independently of time since HTx.

Prognostic value of exercise myocardial deformation and haemodynamics in long‐term heart‐transplanted patients