Adam Høgsbro Laursen1, Marie Bayer Elming2, Rasmus Sejersten Ripa3, Philip Hasbak3, Andreas Kjær3, Lars Køber2, Jacob Louis Marott4, Jens Jakob Thune2,5,6, Martin Hutchings7. 1. Department of Hematology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen Ø, Denmark. adam.hoegsbro.laursen.01@regionh.dk. 2. Department of Cardiology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen Ø, Denmark. 3. Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen Ø, Denmark. 4. Copenhagen City Heart Study, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Nordre Fasanvej 57, 2000, Frederiksberg, Denmark. 5. Department of Cardiology, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Nordre Fasanvej 57, 2000, Frederiksberg, Denmark. 6. Department of Cardiology, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Bispebjerg Bakke 23, 2400, Copenhagen NV, Denmark. 7. Department of Hematology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen Ø, Denmark.
Abstract
BACKGROUND: Doxorubicin is a cornerstone in lymphoma treatment, but is limited by dose-dependent cardiotoxicity. Rubidium-82 positron emission tomography (82Rb PET) assesses coronary microvascular function through absolute quantification of myocardial perfusion and myocardial perfusion reserve (MPR). Doxorubicin-induced microvascular injury represents a potential early marker of cardiotoxicity. METHODS AND RESULTS: We included 70 lymphoma patients scheduled for doxorubicin-based treatment. Cardiotoxicity was evaluated with 82Rb PET myocardial perfusion imaging during rest and adenosine stress before chemotherapy and shortly after the first doxorubicin exposure. Patients with a MPR decline > 20% were defined as having a low threshold for cardiotoxicity. In the 54 patients with complete data sets, MPR was significantly lower after the initial doxorubicin exposure (2.69 vs 2.51, P = .03). We registered a non-significant decline in stress perfusion (3.18 vs 3.02 ml/g/min, P = .08), but no change in resting myocardial perfusion. There were 13 patients with a low cardiotoxic threshold. These patients had a significantly higher age, but were otherwise similar to the remaining part of the study population. CONCLUSION: Decreases in MPR after initial doxorubicin exposure in lymphoma patients may represent an early marker of doxorubicin-induced cardiotoxicity. The prognostic value of acute doxorubicin-induced changes in MPR remains to be investigated.
BACKGROUND:Doxorubicin is a cornerstone in lymphoma treatment, but is limited by dose-dependent cardiotoxicity. Rubidium-82 positron emission tomography (82Rb PET) assesses coronary microvascular function through absolute quantification of myocardial perfusion and myocardial perfusion reserve (MPR). Doxorubicin-induced microvascular injury represents a potential early marker of cardiotoxicity. METHODS AND RESULTS: We included 70 lymphomapatients scheduled for doxorubicin-based treatment. Cardiotoxicity was evaluated with 82Rb PET myocardial perfusion imaging during rest and adenosine stress before chemotherapy and shortly after the first doxorubicin exposure. Patients with a MPR decline > 20% were defined as having a low threshold for cardiotoxicity. In the 54 patients with complete data sets, MPR was significantly lower after the initial doxorubicin exposure (2.69 vs 2.51, P = .03). We registered a non-significant decline in stress perfusion (3.18 vs 3.02 ml/g/min, P = .08), but no change in resting myocardial perfusion. There were 13 patients with a low cardiotoxic threshold. These patients had a significantly higher age, but were otherwise similar to the remaining part of the study population. CONCLUSION: Decreases in MPR after initial doxorubicin exposure in lymphomapatients may represent an early marker of doxorubicin-induced cardiotoxicity. The prognostic value of acute doxorubicin-induced changes in MPR remains to be investigated.
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