p.82 抽出テキスト

May 3, 2022 Circulation. 2022;145:e895–e1032. DOI: 10.1161/CIR.0000000000001063 e976

CLINICAL STATEMENTS AND GUIDELINES

outcomes.1,2,38 Patients who develop HF while receiving potentially cardiotoxic therapies should have these therapies discontinued while a diagnostic workup is undertaken to ascertain the cause of HF and initiate GDMT. The complex decision to resume, modify, or permanently discontinue therapy by the primary oncologist should be done in a patient-centered approach in concert with a cardiovascular specialist in cardio-oncology. Factors impacting the decision include the severity of cancer therapy–related cardiomyopathy and the response to neurohormonal blockade, the offending agent’s specific mechanism of injury, the patient’s comorbid conditions and cancer-related prognosis and, lastly, the availability of alternative noncardiotoxic treatment options. However, the clinical significance of asymptomatic cancer therapy–related cardiomyopathy that is identified on routine monitoring is less clear. This is most apparent in patients receiving trastuzumab in whom asymptomatic decreases in LVEF can occur in >10% of patients yet result in a high recovery rate and low rate of discontinuation of therapy.1,2 Accordingly, trastuzumab is often continued in patients deemed low risk while neurohormonal blockade is initiated. Conversely, patients diagnosed with immune checkpoint-related myocarditis typically have the offending agents discontinued indefinitely, given the associated high mortality.39,40 2.	 Studying the effectiveness of neurohormonal therapies specifically in patients with the CTRC gene is challenging given the relative infrequency of events, heterogeneity of offending agents, the poorly understood pathophysiology, and the overlap with comorbid CVD. Available data in patients with anthracycline and trastuzumabinduced cardiomyopathy suggest beta blockers and ACEi are effective in improving LV dysfunction.2–4 Given the dearth of data specific to cancer therapy–related cardiomyopathy for other GDMT, their use should align with the HFrEF management guidelines. Initiation and uptitration of standard HF therapies remains the mainstay of treatment in patients with cancer therapy–related cardiomyopathy or LVEF <50%, with close monitoring of cardiac function to guide discussions with oncology on the resumption of, or choice of, subsequent cancer therapies.2

3.	 Pretherapy quantification of LVEF in patients receiving potentially cardiotoxic cancer therapies serves 4 purposes: 1) pretherapy risk stratification and diagnosis of preexisting cardiomyopathy, 2) establish a reference baseline to which reevaluations can be compared, 3) initiate cardioprotective medications before cancer therapy, and 4) guide choice of cancer therapy. Echocardiography is recommended as the firstline modality for LVEF assessment given its availability, safety, relatively low cost, and its ability to provide structural and functional information beyond LVEF.2,5–16,41–47 The risk of cancer therapy–related cardiomyopathy varies greatly across cancer therapies and is modified by preexisting cardiovascular risk factors (Table 29). Pretherapy LVEF is a strong predictor of major adverse cardiovascular events in patients receiving potentially cardiotoxic therapies.2,5–10,42–47 The clinical use and cost-effectiveness of systematic screening in all patients, however, is unclear.11–16

Table 28.  Cancer Therapies Known to Be Associated With Cardiomyopathy

Class Cardiac Function Monitoring Often Performed in Clinical Practice

Agent(s) Pretherapy Serial

Anthracyclines55–57 Doxorubicin, epirubicin X X Alkylating agents58–60 Cyclophosphamide, ifosfamide, melphalan X Antimicrotubule agents.61,62 Docetaxel Antimetabolites63–72 Fluorouracil, capecitabine, fludarabine, decitabine Anti-HER2 agents73–76 Trastuzumab, pertuzumab X X Monoclonal antibodies77 Rituximab Tyrosine-kinase inhibitors78–100 Dabrafenib, dasatinib, lapatinib, pazopanib, ponatinib, sorafenib, trametinib, sunitinib, vandetanib, imatinib, vandetanib Immune checkpoint inhibitors39,40,101 Nivolumab, ipilimumab, pembrolizumab Protease inhibitors102–106 Bortezomib, carfilzomib Endocrine therapy107–111 Goserelin, leuprolide, flutamide, bicalutamide, nilutamide Chimeric antigen receptor T-cell therapy.112,113 Tisagenlecleucel, axicabtagene ciloleucel X Hematopoietic stem cell transplantation7,44,114–119 Hematopoietic stem cell transplantation X Radiation7,44,114–119 Chest Downloaded from http://ahajournals.org by on October 7, 2026