Abstract Body (Do not enter title and authors here): Background: Ticagrelor has been reported to cause shortness of breath (SOB) in 6 to 9 % of patients. Precise mechanisms are not enirely understood. We hypothesize that cardiopulmonary exercise testing (CPET) may be helpful in clinical assessment of patients reporting SOB on ticagrelor.
Case presentation: 66-yo female with history of arterial hypertension, DM type 2 and prior MI presented with STEMI and successfully underwent urgent PCI of RCA and LAD. The patient received ticagrelor in loading dose followed by 90 mg b.i.d plus low-dose aspirin. Just after PCI she developed SOB with no evidence of acute cardiac or respiratory compromise. After discharge the patient continued to experience SOB impairing daily activities. In 6 months she was re-assessed. Clinical investigation (physical exam, blood tests, echo, CXR, spirometry) showed no abnormalities that could explain SOB. CPET despite good effort showed low VO₂ peak (7,8 ml*min/kg; 49% from predicted), undetectable anaerobic threshold (AT), severely impaired ventilatory efficacy (VE/VCO₂=50,1) and marked hyperventilation (resting RER=1,0; PetCO₂=18,0 mmHg at rest and 22,4 mmHg at peak load). Exercise EKG, blood pressure response, SpO₂ and breathing reserve were normal. Once the patient was switched from ticagrelor to clopidogrel she reported significant improvement. CPET one week after showed increase in VO₂ peak up to 12,5 ml/kg/min., AT of 11,1 ml*min/kg, better ventilatory efficacy (VE/VCO₂=37,1) and less hyperventilation (PetCO₂ 28,1 mmHg at rest and 28,8 mmHg at peak load). CPET performed one month later showed further improvement in VO₂ peak to 13,2 ml*min/kg, normal VE/VCO₂ and no signs of hyperventilation.
Discussion: it is believed that ticagrelor-induced dyspnea can be driven by 2 potential mechanisms, first related to inhibition of adenosine reuptake, second - to sensory neuron P2Y12 inhibition. It occurs early after starting the medication and is not associated with structural cardiopulmonary abnormalities. Previous small data showed evidence of Cheyne-Stokes respiration during both night and day related to ticagrelor. Symptoms usually are dose-dependent and disappear after discontinuation of ticagrelor. In our case the patient demonstrated reversible hyperventilation and reduced exercise capacity associated with ticagrelor that was confirmed with CPET.
Conclusion: CPET allows differentiating SOB in patients treated with ticagrelor. Further investigations are required to confirm this hypothesis.