Cancer therapy-related cardiotoxicity has been presenting a major problem in cancer survivors, who constitute a growing population caused by a significant improvement in cancer therapy during the past decades. Although some listing criteria have been defined for these patients, it is still a compelling decision to list patients with a complex cancer anamnesis. We describe herein a childhood cancer survivor after a cancer anamnesis with 2 different malignancies and an end-stage heart failure following chemoradiotherapy who was successfully treated with orthotopic heart transplant.
Key words : Cardiomyopathy, Chemotherapy, Orthotopic heart transplant, Radiotherapy
Innovations in chemotherapy within the past decades have substantially improved survival for various cancers. A substantial number of survivors develop therapy-related cardiomyopathy with onset even many years after treatment. Although cancer therapy-related cardiotoxicity presents a small proportion of end-stage heart failures, this population has the lowest survival rate among cardiomyopathies.1
Although the left ventricular assist device has emerged as a therapy option for end-stage heart failure and has increasingly been utilized, heart transplant remains the gold standard therapy also for cancer therapy-related cardiotoxicity, with survival rates similar to those with further underlying diseases causing heart failure.2 However, the risk of recurrence of primary malignancy as a result of posttransplant immunosuppression treatment has to be clarified before transplant listing. Coupled with the growing number of cancer survivors, a concrete management strategy in cases of cancer therapy-related cardiotoxicity has not been well described.
We report on a childhood cancer survivor who was successfully treated with orthotopic heart transplant.
A 29-year-old white female patient was admitted to our cardiology department with imminent cardiogenic shock due to cancer therapy-related cardiotoxicity.
Her history included surgical nephrectomy for clear cell renal sarcoma (clear cell sarcoma of the kidney) at the age of 7 months. In detail, the tumor had myxoid pattern, stage II, with no residual tumor apparent at or beyond the margins of excision. Treatment consisted of adjuvant chemotherapy (actinomycin D, vincristine sulfate, doxorubicin hydrochloride, and cyclophosphamide). One year later, bone metastases in left scapula and right maxillary sinus were detected and treated with combination of 6 months of chemotherapy with ifosfamide and doxorubicin (cumulative dose 200 mg) and fractionated radiotherapy up to a cumulative dose of 46 Gy. At the age of 9 years, a right thyroid lobectomy was conducted for curative treatment of papillary carcinoma.
After 11 years of healthiness, at the age of 20 years, she was hospitalized with a sudden motor aphasia and right arm weakness. Computed tomography angiography of the cerebral arteries illustrated an ischemic stroke due to middle cerebral artery M1 segment occlusion, which could be recanalized after an immediate interventional thrombectomy and stenting. Further diagnosis revealed a heterozygous factor V Leiden mutation. Moreover, a new-onset massive enlarged left atrium (6 cm) with thrombotic material in cavity despite sinus rhythm and a mitral valve regurgitation grade 2 with a global normal left ventricular function were diagnosed. Because of existing atrial thrombosis, effective anticoagulation with warfarin was initiated. During the next 4 years, she was followed annually with cardiological examinations.
At the age of 24 years, she was hospitalized with a cardiac decompensation due to reduced left ventricular ejection fraction. Magnetic resonance imaging demonstrated myocardial fibrosis. With an endomyocardial biopsy, myocardial fibrosis was confirmed, and myocarditis could be excluded. Coronary angiography did not reveal any pathological findings. After adjustment of heart failure medications and clinical recompensation, the patient was discharged. In the course of time, her left ventricular function gradually worsened and she was hospitalized again with cardiogenic shock at the age of 29 years.
Immediately after admission to our cardiology department, the patient went into cardiac arrest and was resuscitated for 2 minutes until return of spontaneous circulation. Afterward, she was in a stable condition and treated with norepinephrine and dobutamine. After right heart catheterization confirmed a severe cardiogenic shock with a cardiac index of 1.7 L/min/m2, we decided to implant a percutaneous Impella CP (Abiomed, Danvers, MA, USA) via the femoral artery for left ventricular unloading and mechanical support as a less invasive method (instead of venoarterial extracorporeal membrane oxygenation). The patient was maintained on dobutamine for right ventricular support. With the use of both Impella and dobutamine, it was possible to reverse the increase of lactate; additionally, intermittent atrial fibrillation was treated with amiodarone. Despite ongoing Impella support, persistent atrial fibrillation and right ventricular deterioration due to pulmonary hypertension caused recurrent decompensations, providing the basis for a “high urgent” listing for heart transplant. Although weaning and explantation of Impella was possible after 2 weeks, the high urgent status could be maintained because of the permanent need for dobutamine application.
After another 27 days had passed, the patient underwent orthotopic heart transplant. After an uncomplicated perioperative course, the patient was weaned from ventilation on postoperative day 1. On postoperative day 10, she was transferred from the intensive care unit to a standard ward. Her further postoperative course was uneventful.
Three weeks after heart transplant, our patient was discharged to a rehabilitation clinic to improve her daily physical activities. Currently, she is at home, working part-time, and doing well 9 months after transplant.
This report illustrates a successful heart transplant in a childhood cancer survivor with a complex cancer anamnesis and cancer therapy-related cardiotoxicity.
Cardiotoxicity is a major problem among cancer survivors, which may be induced by chemotherapy, radiotherapy, or both. The risk of anthracycline-induced heart failure increases as the cumulative dose administered increases: 3% to 5% with 400 mg/m2 and as high as 18% to 48% at 700 mg/m2.3 However, there are significant differences depending on the individual patient, particularly in younger children as well as in older patients with known comorbidities who have an increased risk for cardiotoxicity.4
Our patient went through multiple chemotherapy cycles with doxorubicin and left-side thoracic fractionated radiotherapy because of her complex cancer anamnesis in childhood. Although the initial identification of an isolated massive enlarged left atrium and myocardial fibrosis in magnetic resonance imaging and endomyocardial biopsy may suggest a radiotherapy-induced cardiomyopathy, the main cause of her heart disease cannot be clearly defined.
In general, recurrence of malignant diseases during treatment with posttransplant immunosuppression in cancer survivors represents a significant problem. In addition to a potential relapse of thyroid carcinoma when treated with immunosuppressive drugs, posttransplant lymphoproliferative disorders are one of the most important malignancies after solid-organ transplant. Lymphoma accounts for 21% of all malignancies in solid-organ transplant recipients compared with 5% in immunocompetent individuals.5
Therefore, an active or recent solid-organ or blood malignancy within 5 years has been accepted as an absolute contraindication for heart transplant by previous listing criteria.6 On the other hand, in a large multi-institutional registry for chemotherapy-induced cardiomyopathy that included 232 heart transplants, Oliveira and colleagues found only one instance of recurrence in a patient with previous breast cancer at 1 year follow-up.7 A larger United Network for Organ Sharing analysis from 1987 to 2011 confirmed these findings.8 Recurrence was also considered in the 2016 International Society for Heart and Lung Transplantation listing criteria, which authorizes to list patients with diverse natures of preexisting neoplasms after an oncological statement that stratifies each cancer patient’s individual risk of malignancy recurrence. The specific amount of time before a possible heart transplant after neoplasm remission will depend on factors such as tumor type, response to therapy, and negative metastatic work-up. Therefore, no arbitrary time period for observation has so far been recommended.9
In our case, interdisciplinary collaborations across cardiac surgery, cardiology, and oncology departments played a decisive role for the providential prognosis. The initial heart team decision to treat cardiogenic shock only with Impella and not to implant a venoarterial extracorporeal membrane oxygenation potentially prevented possible serious complications. Dobutamine was chosen to improve right ventricular contractility and lower filling pressures.10 Furthermore, despite approximately 20 years of cancer freedom, an oncological consultation after such a complex cancer anamnesis could support our decision to list her for heart transplant after an interdisciplinary evaluation. By means of this collaboration, the patient underwent an uneventful postoperative course, and at the moment she is doing well. Further follow-ups are needed to observe the mid- to long-term outcomes, particularly with regard to tumor recurrence.
This report illustrates a successful heart transplant in a challenging case of a cardiogenic shock due to cancer therapy-related cardiotoxicity after a complex childhood cancer anamnesis with 2 different malignancies. Furthermore, this case demonstrates the importance of close cooperation of oncologists, cardiologists, and cardiac surgeons to improve the outcome of such patients with a complex cancer anamnesis.
DOI : 10.6002/ect.2020.0062
From the 1Department of Cardiac Surgery, Heinrich-Heine University Hospital,
Düsseldorf, Germany; and the 2Department of Cardiology, Pulmonary Diseases,
Vascular Medicine, Heinrich-Heine University Hospital, Düsseldorf, Germany
Acknowledgements: The authors have no sources of funding for this study and have no conflicts of interest to declare.
Corresponding author: Udo Boeken, Department of Cardiac Surgery, Heinrich-Heine University Hospital, Moorenstrasse 5, 40225 Düsseldorf, Germany