ASAIO Journal 2014
Case Series
Cancer in End-Stage Heart Failure Patients Supported by Left Ventricular Assist Devices Renzo Y. Loyaga-Rendon,* Chakradhari Inampudi,† Jose A. Tallaj,* Deepak Acharya,* and Salpy V. Pamboukian*
The percentage of elderly patients receiving left ventricular assist devices (LVADs) has increased; thus, a rise in the frequency of elderly prevalent diseases would be expected in LVAD-supported patients. Cancer is the second leading cause of death in the United States, and the frequency of cancer and the mortality rate of malignancies increase with age. We describe the clinical characteristics of eight patients who were diagnosed of cancer after LVAD implantation. Skin, esophageal, central nervous system (CNS), hematological and renal malignancies were observed. After careful consideration, these patients underwent surgical resections, radiotherapy, radiofrequency ablation, and chemotherapy with variable results. Patients who developed cancer were older males who received LVAD predominantly as destination therapy. Skin cancer and hematological malignancy were managed with standard oncologic treatment. Renal cell carcinoma was monitored, and a CNS tumor was treated aggressively but as expected had a poor outcome. Esophageal cancer, although localized, represented a serious therapeutic challenge, as patients were unable to undergo a potentially curative surgical procedure because of the anatomic location of malignancy. More information is needed regarding the outcomes and best treatment strategies for this newly identified population. ASAIO Journal 2014; 60:609–612.
The concomitant diagnosis of cancer in LVAD-supported patients poses multiple challenges both to the patient and to the treating center. This is a case series describing the de novo diagnosis of cancer in patients who were supported by LVAD. Case Series During March 2006 and September 2012, 118 patients received continuous flow LVADs at our institution. Of these, eight patients were diagnosed with cancer after LVAD implantation. Clinical characteristics of these eight patients at the time of implantation are described in Table 1. Patients who developed cancer were older than patients who did not develop cancer, and there was a trend for more frequent implantation of LVADs as destination therapy (DT). Patients who developed cancer were all male. The median time of support before the diagnosis of cancer was 6 months (range 1–59), and the median time of support after the diagnosis of cancer was 14 months (range 7–58). The characteristics of the malignancies, treatment, outcomes, and time of support after the diagnosis of cancer are presented in Table 2. Patients with localized and easily resectable disease (skin cancer) or multiple myeloma received standard therapy used for non-LVAD patients and had the best long-term outcome. A patient with slow growing tumor (renal cell carcinoma) was followed conservatively. Two patients developed localized cancer of the esophagus and received nonstandard treatment, as surgical resection was felt to be high risk in the presence of LVAD. One patient had an aggressive central nervous system malignancy, and in spite of the presence of LVAD he underwent standard cancer therapy including extensive resection of brain tumor with a poor outcome. Anticoagulation therapy varied among patients; the international normalized ratio goals and presence of thrombotic events in patients who were diagnosed with cancer are shown in Table 3.
Key Words: left ventricular assist device, cancer
Left ventricular assist devices (LVADs) are an established treat-
ment for end-stage heart disease. The percentage of elderly patients (>60 years old) receiving LVADs has increased and represents 50% of all the LVAD recipients (http://www.uab. edu/intermacs 5/16/2013). Thus, an increase in the frequency of elderly prevalent diseases will be observed in LVAD patients. Cancer is the second leading cause of death in the United States. The frequency of cancer increases with age, and the mortality rate of malignant neoplasms is highest in patients older than 65 years old (http://www.cdc.gov/nchs/data/nvsr/ nvsr61/nvsr61_06.pdf).
Discussion Left ventricular assist devices are superior to medical therapy in the management of end-stage heart failure patients who are not candidates for heart transplantation.1 According to some estimations, the theoretical number of potential beneficiaries of this new technology in the United States may vary between 250,000 and 300,000 patients.2 After the approval of Heartmate-II for DT by the Food and Drug Administration the number of implants has increased dramatically and in 2012 for the first time it surpassed the number of transplanted hearts. The increment in LVAD implantation has occurred predominantly in elderly patients.3 As noted in this report, patients who developed cancer where older and received LVAD as destination therapy more frequently. Thus, if the current trend continues it would be expected that in near future we could encounter more patients being diagnosed with cancer while on LVAD support.
From the *Section of Advanced Heart Failure, Heart Transplantation, Mechanical Circulatory Support, and Pulmonary Vascular Disease, University of Alabama, Birmingham, Alabama; and †Hospitalist Medicine, University of Alabama, Birmingham, Alabama. Submitted for consideration September 2013; accepted for publication in revised form May 2014. Disclosure: The authors have no conflicts of interest to report. Correspondence: Renzo Y. Loyaga-Rendon, University of Alabama, 321 Tinsley Harrison Tower, 1900 University Boulevard, Birmingham, AL 35294. Email: [email protected]. Copyright © 2014 by the American Society for Artificial Internal Organs DOI: 10.1097/MAT.0000000000000116
609
610
LOYAGA-RENDON et al.
Table 1. Clinical Characteristics in Patients Diagnosed With Cancer While on LVAD Support
Age at implant Male (%) ICMP (%) DT strategy (%)
LVAD No Cancer N = 110
LVAD and Cancer N=8
p
51.8 ± 15.1 84 (76.3) 49 (44.5) 40 (36.3)
68.6 ± 4.9 8 (100) 6 (75) 6 (75)
0.002 0.19 0.14 0.054
Groups were compared with t-test. DT, destination therapy; ICMP, ischemic cardiomyopathy; LVAD, left ventricular assist device.
Patients who had a de novo diagnosis of cancer were all males; this gender preference did not achieve statistical significance and may be due to the known comparative lower frequency of LVAD implantation in women (23.6%). In addition, uterine and ovarian cancers are the 4th and 8th most common malignancies in women (www.cdc.gov/uscs). Female patients supported by LVAD receive a comprehensive examination at follow up but frequently does not include a gynecological examination or imaging targeting the reproductive organs, and this could have led to an underestimation in the frequency of malignancy in this gender. Tobacco abuse is a known risk factor for cancer and coronary artery disease;4 thus, it would be expected that patients with ischemic cardiomyopathy may have an increased risk of developing cancer. In our report, four out of six patients with ischemic cardiomyopathy had remarkable history of tobacco abuse; however, given the low number of patients involved in these report we cannot draw stronger conclusions. One of the questions that arise after the diagnosis of cancer in a patient with an LVAD is, Would the presence of an LVAD preclude these patients from receiving standard oncologic treatments? The oncologic treatment plan will depend on the type, location, and staging of the malignancy. As described here, the type of malignancies varied significantly from skin lesions, which were treated with local resection, to invasive
malignant central nervous system tumors that required extensive surgeries, radiation, and chemotherapy. The location of the malignancy is also important; two of our patients developed localized adenocarcinoma of the esophagus, which under usual conditions could have been potentially cured with surgical resection5 and chemoradiation. One of our patients had early stage esophageal cancer T1N0M0; an interdisciplinary team decided that the best treatment alternative would be the use of endoscopic radiofrequency ablation (RFA) for initial management, deferring esophagectomy versus brachytherapy in case persistence of cancer in surveillance endoscopies. This patient died suddenly because of device malfunction. The second patient had locally invasive disease T3N0M0; in this case, chemoradiation was considered as first treatment option. In both cases, the proposed surgery would have been the Ivor–Lewis transthoracic esophagetomy, which combines a laparotomy with a right thoracotomy and an intrathoracic anastomosis.6 Given the localization of the LVAD components in the vicinity of the esophagus, it was considered that these patients were high-risk surgical candidates. The surgery’s requirement of extensive dissection and reconstruction, concerns about bleeding, perfusion, and wound healing and risks of dehiscence made us opt for other treatment approaches. The biology of the tumor will also determine the treatment strategy. One of our patients had a renal cell carcinoma, which is potentially curable with surgical intervention. However, given the slow growing nature of this tumor, observation is an alternative in high risk surgical candidates.7 In our patient, observation was favored because it was felt that undergoing an extensive resection would be riskier than expectant management. A second question is would the treatment for cancer impair or affect the LVAD function? Cancer is usually treated with surgical resection, radiotherapy, or chemotherapy used as single or in combination strategies. Left ventricular assist device patients need anticoagulation and antiplatelet therapy.8 LVADs produce hematological changes
Table 2. Characteristics of Malignant Neoplasms in Patients Who Were Supported by LVAD Cancer Patient
Type
1 2
Basal cell carcinoma × 2 Malignant melanoma × 2
3
Malignant melanoma Poorly differentiated metastatic adenocarcinoma Adenocarcinoma of the esophagus T1N0M0 Adenocarcinoma of the esophagus T3N0M0 Glioblastoma multiforme grade IV
4 5 6 7
Multiple myeloma
8
Renal cell carcinoma
Time of Support Before Cancer (months)
Time of Support After Cancer (months)
Treatment
Outcome
Resection Resection
Cured, Alive Cured Dead (trauma) Hospice Dead
12 13
36 58
3
13
LVAD failure Dead
59
6
Chemoradiation Doxetacel and 5FU
Hospice Dead
5
15
Craniotomy and mass resection Radiation Temozolomide Dexamethasone, valcade, cyclophosphamide Follow-up
Hospice Dead
6
14
Alive
1
21
Alive
2
7
Resection of melanoma Hospice Radiofrequency ablation
5FU, 5-fluorouracil; LVAD, left ventricular assist device.
611
CANCER IN LVAD Table 3. Anticoagulation Parameters in Patients Supported by LVAD Diagnosed With Cancer Anticoagulation Parameters (INR)
Patient
Before LVAD
After LVAD
After Cancer Diagnosis
1 2 3
~1 2–3 ~1
1.5–2.5 1.5–2.5 1.7–2.3
4 5 6 7 8
~1 1.1 2–3 2–3 ~1
~1 because of GIB 1.5–2.5 ~1 because of GIB 1.5–2 1.8–2 because of SAH
1.5–2.5 ~1 because of GIB 2–2.5 because of LVAD thrombosis ~1 ~1 because of GIB ~1 1.5–2 2–2.5 after PE
Thrombotic Events None None LVAD thrombosis None None None None PE DVT
DVT, deep venous thromboembolism; GIB, gastrointestinal bleeding; INR, international normalized ratio; LVAD, left ventricular assist device; SAH, subarachnoidal hemorrhage; PE, pulmonary embolism.
such as acquired Von Willebrand factor deficiency, which predispose to bleeding.9 Thus, undergoing any surgical resection would pose risks for excessive bleeding. On the other hand, cancer is associated with an increased prothrombotic state,10 and holding anticoagulation may increase further the risk of pump thrombosis; this is particularly important in light of recent reports observing an increase incidence of pump thrombosis in LVADsupported patients.11 Limited information exists regarding the safety of noncardiac surgery in patients who are being supported by LVAD.12 The safety of undergoing an oncological resection in LVAD-supported patients will depend on the location of cancer, extension of the surgical procedure (risk for bleeding), and the length of time of anticoagulation (risk for pump thrombosis). A case report suggested the feasibility of oncological surgical interventions in LVAD-supported patients.13 Three of our patients had localized skin cancer, and resection was performed on anticoagulation and without complications. One of our patients had a central nervous system lesion; he underwent craniotomy and resection of brain tumor off anticoagulation and antiplatelet therapies; there were no bleeding complications. Anticoagulation was not intensified by the diagnosis of cancer but rather decreased in some patients because of bleeding concerns (esophageal cancer and glyoblastoma multiforme). Two of our patients had thrombotic complications; our patient with renal cell carcinoma had a deep venous thromboembolism and a pulmonary embolism; these events occurred in the setting of mild anticoagulation given recent history of gastrointestinal bleed and subarachnoidal hemorrhage. Another patient experienced an acute LVAD thrombosis in the setting of bacteremia and underwent emergent LVAD exchange. This patient had a melanoma resected 1 year before. Three months after the thrombotic event, metastatic undifferentiated adenocarcinoma was diagnosed and the patient was sent to hospice care. Because of our small number of patients, it is not possible to conclude if these events were associated to the de novo cancer diagnosis. Radiation therapy is frequently used in the management of cancer. Ionizing radiation can lead to malfunction of other types of devices such as cardiac defibrillators or pacemakers.14 A priori it may appear that there should not be any barrier to receive radiation therapy in LVAD-supported patients. Continuous flow devices have a rotor, which contains a magnet that is rotated by electromagnetic forces. The driveline contains electrical wires and other materials including polyurethane and silicone. In addition, the controller has a delicate microprocessor
that operates the pump and stores data. There is limited information regarding the effects of ionizing radiation on the LVAD equipment including, rotor, drivelines, leads, and controllers. Radiation dose and irradiated area may be important in determining the effects over the LVAD components, but scattered radiation may also play a role. One study reported stability of LVADs after proton beam radiation therapy; specifically five heartware devices were radiated to a cumulative dose of 70Gy. Interrogation of devices showed no changes in function.15 Similarly, another report demonstrated that γ radiation of an LVAD did not change any parameters of the device16 and carefully analyzed the components and materials of a HeartmateII device; they found changes in the driveline materials that were considered not significant enough to compromise lead durability, although no comprehensive fatigue testing was performed. Two of our patients received external radiation, one to the chest and another to the head. Devices were interrogated before and after radiation treatments, and none of them had device malfunction after radiation therapy. Radiofrequency ablation (RFA) of the esophagus has been used for the management of Barret’s esophagus and in some cases of intramucosal carcinoma in combination with endoscopic mucosal resection.17 One of our patients with esophageal cancer received RFA to the esophagus, and he died suddenly few weeks after the treatment. Autopsy determined that the cause of death was device malfunction. Although unlikely, the contribution of RFA to the device malfunction is unclear. Chemotherapy is a cornerstone in the management of most malignancies and results in immunosuppression and susceptibility to infections. Left ventricular assist device driveline infections are common, and up to 19% of patients will have a driveline infection at 1 year of support affecting the overall survival of these patients.18 In addition, pocket infections, blood stream infections,19 and endocarditis have been reported in LVAD-supported patients.20 Thus, patients who are receiving chemotherapy and supported by LVAD may be at increased risk for infections when compared with other cancer patients. In our series, three patients received low intensity chemotherapy. We did not observe any worsening in LVAD-related infections in these patients. It is well known that some chemotherapeutic agents such as Adriamycin can have direct cardiac toxicity in a dose-dependent manner.21 In our series, no patient received antracyclins or other known cardiotoxic chemotherapeutic agents; however, a theoretical question arises, could a LVAD-suppported
612
LOYAGA-RENDON et al.
patient receive a potentially cardiotoxic chemotherapeutic agent? It would be important to point out that in LVAD patients the right ventricle is still unsupported, and thus, chemotherapy could still cause cardiotoxicity with potential hemodynamic significance. Recent history of cancer (
Case Series
Cancer in End-Stage Heart Failure Patients Supported by Left Ventricular Assist Devices Renzo Y. Loyaga-Rendon,* Chakradhari Inampudi,† Jose A. Tallaj,* Deepak Acharya,* and Salpy V. Pamboukian*
The percentage of elderly patients receiving left ventricular assist devices (LVADs) has increased; thus, a rise in the frequency of elderly prevalent diseases would be expected in LVAD-supported patients. Cancer is the second leading cause of death in the United States, and the frequency of cancer and the mortality rate of malignancies increase with age. We describe the clinical characteristics of eight patients who were diagnosed of cancer after LVAD implantation. Skin, esophageal, central nervous system (CNS), hematological and renal malignancies were observed. After careful consideration, these patients underwent surgical resections, radiotherapy, radiofrequency ablation, and chemotherapy with variable results. Patients who developed cancer were older males who received LVAD predominantly as destination therapy. Skin cancer and hematological malignancy were managed with standard oncologic treatment. Renal cell carcinoma was monitored, and a CNS tumor was treated aggressively but as expected had a poor outcome. Esophageal cancer, although localized, represented a serious therapeutic challenge, as patients were unable to undergo a potentially curative surgical procedure because of the anatomic location of malignancy. More information is needed regarding the outcomes and best treatment strategies for this newly identified population. ASAIO Journal 2014; 60:609–612.
The concomitant diagnosis of cancer in LVAD-supported patients poses multiple challenges both to the patient and to the treating center. This is a case series describing the de novo diagnosis of cancer in patients who were supported by LVAD. Case Series During March 2006 and September 2012, 118 patients received continuous flow LVADs at our institution. Of these, eight patients were diagnosed with cancer after LVAD implantation. Clinical characteristics of these eight patients at the time of implantation are described in Table 1. Patients who developed cancer were older than patients who did not develop cancer, and there was a trend for more frequent implantation of LVADs as destination therapy (DT). Patients who developed cancer were all male. The median time of support before the diagnosis of cancer was 6 months (range 1–59), and the median time of support after the diagnosis of cancer was 14 months (range 7–58). The characteristics of the malignancies, treatment, outcomes, and time of support after the diagnosis of cancer are presented in Table 2. Patients with localized and easily resectable disease (skin cancer) or multiple myeloma received standard therapy used for non-LVAD patients and had the best long-term outcome. A patient with slow growing tumor (renal cell carcinoma) was followed conservatively. Two patients developed localized cancer of the esophagus and received nonstandard treatment, as surgical resection was felt to be high risk in the presence of LVAD. One patient had an aggressive central nervous system malignancy, and in spite of the presence of LVAD he underwent standard cancer therapy including extensive resection of brain tumor with a poor outcome. Anticoagulation therapy varied among patients; the international normalized ratio goals and presence of thrombotic events in patients who were diagnosed with cancer are shown in Table 3.
Key Words: left ventricular assist device, cancer
Left ventricular assist devices (LVADs) are an established treat-
ment for end-stage heart disease. The percentage of elderly patients (>60 years old) receiving LVADs has increased and represents 50% of all the LVAD recipients (http://www.uab. edu/intermacs 5/16/2013). Thus, an increase in the frequency of elderly prevalent diseases will be observed in LVAD patients. Cancer is the second leading cause of death in the United States. The frequency of cancer increases with age, and the mortality rate of malignant neoplasms is highest in patients older than 65 years old (http://www.cdc.gov/nchs/data/nvsr/ nvsr61/nvsr61_06.pdf).
Discussion Left ventricular assist devices are superior to medical therapy in the management of end-stage heart failure patients who are not candidates for heart transplantation.1 According to some estimations, the theoretical number of potential beneficiaries of this new technology in the United States may vary between 250,000 and 300,000 patients.2 After the approval of Heartmate-II for DT by the Food and Drug Administration the number of implants has increased dramatically and in 2012 for the first time it surpassed the number of transplanted hearts. The increment in LVAD implantation has occurred predominantly in elderly patients.3 As noted in this report, patients who developed cancer where older and received LVAD as destination therapy more frequently. Thus, if the current trend continues it would be expected that in near future we could encounter more patients being diagnosed with cancer while on LVAD support.
From the *Section of Advanced Heart Failure, Heart Transplantation, Mechanical Circulatory Support, and Pulmonary Vascular Disease, University of Alabama, Birmingham, Alabama; and †Hospitalist Medicine, University of Alabama, Birmingham, Alabama. Submitted for consideration September 2013; accepted for publication in revised form May 2014. Disclosure: The authors have no conflicts of interest to report. Correspondence: Renzo Y. Loyaga-Rendon, University of Alabama, 321 Tinsley Harrison Tower, 1900 University Boulevard, Birmingham, AL 35294. Email: [email protected]. Copyright © 2014 by the American Society for Artificial Internal Organs DOI: 10.1097/MAT.0000000000000116
609
610
LOYAGA-RENDON et al.
Table 1. Clinical Characteristics in Patients Diagnosed With Cancer While on LVAD Support
Age at implant Male (%) ICMP (%) DT strategy (%)
LVAD No Cancer N = 110
LVAD and Cancer N=8
p
51.8 ± 15.1 84 (76.3) 49 (44.5) 40 (36.3)
68.6 ± 4.9 8 (100) 6 (75) 6 (75)
0.002 0.19 0.14 0.054
Groups were compared with t-test. DT, destination therapy; ICMP, ischemic cardiomyopathy; LVAD, left ventricular assist device.
Patients who had a de novo diagnosis of cancer were all males; this gender preference did not achieve statistical significance and may be due to the known comparative lower frequency of LVAD implantation in women (23.6%). In addition, uterine and ovarian cancers are the 4th and 8th most common malignancies in women (www.cdc.gov/uscs). Female patients supported by LVAD receive a comprehensive examination at follow up but frequently does not include a gynecological examination or imaging targeting the reproductive organs, and this could have led to an underestimation in the frequency of malignancy in this gender. Tobacco abuse is a known risk factor for cancer and coronary artery disease;4 thus, it would be expected that patients with ischemic cardiomyopathy may have an increased risk of developing cancer. In our report, four out of six patients with ischemic cardiomyopathy had remarkable history of tobacco abuse; however, given the low number of patients involved in these report we cannot draw stronger conclusions. One of the questions that arise after the diagnosis of cancer in a patient with an LVAD is, Would the presence of an LVAD preclude these patients from receiving standard oncologic treatments? The oncologic treatment plan will depend on the type, location, and staging of the malignancy. As described here, the type of malignancies varied significantly from skin lesions, which were treated with local resection, to invasive
malignant central nervous system tumors that required extensive surgeries, radiation, and chemotherapy. The location of the malignancy is also important; two of our patients developed localized adenocarcinoma of the esophagus, which under usual conditions could have been potentially cured with surgical resection5 and chemoradiation. One of our patients had early stage esophageal cancer T1N0M0; an interdisciplinary team decided that the best treatment alternative would be the use of endoscopic radiofrequency ablation (RFA) for initial management, deferring esophagectomy versus brachytherapy in case persistence of cancer in surveillance endoscopies. This patient died suddenly because of device malfunction. The second patient had locally invasive disease T3N0M0; in this case, chemoradiation was considered as first treatment option. In both cases, the proposed surgery would have been the Ivor–Lewis transthoracic esophagetomy, which combines a laparotomy with a right thoracotomy and an intrathoracic anastomosis.6 Given the localization of the LVAD components in the vicinity of the esophagus, it was considered that these patients were high-risk surgical candidates. The surgery’s requirement of extensive dissection and reconstruction, concerns about bleeding, perfusion, and wound healing and risks of dehiscence made us opt for other treatment approaches. The biology of the tumor will also determine the treatment strategy. One of our patients had a renal cell carcinoma, which is potentially curable with surgical intervention. However, given the slow growing nature of this tumor, observation is an alternative in high risk surgical candidates.7 In our patient, observation was favored because it was felt that undergoing an extensive resection would be riskier than expectant management. A second question is would the treatment for cancer impair or affect the LVAD function? Cancer is usually treated with surgical resection, radiotherapy, or chemotherapy used as single or in combination strategies. Left ventricular assist device patients need anticoagulation and antiplatelet therapy.8 LVADs produce hematological changes
Table 2. Characteristics of Malignant Neoplasms in Patients Who Were Supported by LVAD Cancer Patient
Type
1 2
Basal cell carcinoma × 2 Malignant melanoma × 2
3
Malignant melanoma Poorly differentiated metastatic adenocarcinoma Adenocarcinoma of the esophagus T1N0M0 Adenocarcinoma of the esophagus T3N0M0 Glioblastoma multiforme grade IV
4 5 6 7
Multiple myeloma
8
Renal cell carcinoma
Time of Support Before Cancer (months)
Time of Support After Cancer (months)
Treatment
Outcome
Resection Resection
Cured, Alive Cured Dead (trauma) Hospice Dead
12 13
36 58
3
13
LVAD failure Dead
59
6
Chemoradiation Doxetacel and 5FU
Hospice Dead
5
15
Craniotomy and mass resection Radiation Temozolomide Dexamethasone, valcade, cyclophosphamide Follow-up
Hospice Dead
6
14
Alive
1
21
Alive
2
7
Resection of melanoma Hospice Radiofrequency ablation
5FU, 5-fluorouracil; LVAD, left ventricular assist device.
611
CANCER IN LVAD Table 3. Anticoagulation Parameters in Patients Supported by LVAD Diagnosed With Cancer Anticoagulation Parameters (INR)
Patient
Before LVAD
After LVAD
After Cancer Diagnosis
1 2 3
~1 2–3 ~1
1.5–2.5 1.5–2.5 1.7–2.3
4 5 6 7 8
~1 1.1 2–3 2–3 ~1
~1 because of GIB 1.5–2.5 ~1 because of GIB 1.5–2 1.8–2 because of SAH
1.5–2.5 ~1 because of GIB 2–2.5 because of LVAD thrombosis ~1 ~1 because of GIB ~1 1.5–2 2–2.5 after PE
Thrombotic Events None None LVAD thrombosis None None None None PE DVT
DVT, deep venous thromboembolism; GIB, gastrointestinal bleeding; INR, international normalized ratio; LVAD, left ventricular assist device; SAH, subarachnoidal hemorrhage; PE, pulmonary embolism.
such as acquired Von Willebrand factor deficiency, which predispose to bleeding.9 Thus, undergoing any surgical resection would pose risks for excessive bleeding. On the other hand, cancer is associated with an increased prothrombotic state,10 and holding anticoagulation may increase further the risk of pump thrombosis; this is particularly important in light of recent reports observing an increase incidence of pump thrombosis in LVADsupported patients.11 Limited information exists regarding the safety of noncardiac surgery in patients who are being supported by LVAD.12 The safety of undergoing an oncological resection in LVAD-supported patients will depend on the location of cancer, extension of the surgical procedure (risk for bleeding), and the length of time of anticoagulation (risk for pump thrombosis). A case report suggested the feasibility of oncological surgical interventions in LVAD-supported patients.13 Three of our patients had localized skin cancer, and resection was performed on anticoagulation and without complications. One of our patients had a central nervous system lesion; he underwent craniotomy and resection of brain tumor off anticoagulation and antiplatelet therapies; there were no bleeding complications. Anticoagulation was not intensified by the diagnosis of cancer but rather decreased in some patients because of bleeding concerns (esophageal cancer and glyoblastoma multiforme). Two of our patients had thrombotic complications; our patient with renal cell carcinoma had a deep venous thromboembolism and a pulmonary embolism; these events occurred in the setting of mild anticoagulation given recent history of gastrointestinal bleed and subarachnoidal hemorrhage. Another patient experienced an acute LVAD thrombosis in the setting of bacteremia and underwent emergent LVAD exchange. This patient had a melanoma resected 1 year before. Three months after the thrombotic event, metastatic undifferentiated adenocarcinoma was diagnosed and the patient was sent to hospice care. Because of our small number of patients, it is not possible to conclude if these events were associated to the de novo cancer diagnosis. Radiation therapy is frequently used in the management of cancer. Ionizing radiation can lead to malfunction of other types of devices such as cardiac defibrillators or pacemakers.14 A priori it may appear that there should not be any barrier to receive radiation therapy in LVAD-supported patients. Continuous flow devices have a rotor, which contains a magnet that is rotated by electromagnetic forces. The driveline contains electrical wires and other materials including polyurethane and silicone. In addition, the controller has a delicate microprocessor
that operates the pump and stores data. There is limited information regarding the effects of ionizing radiation on the LVAD equipment including, rotor, drivelines, leads, and controllers. Radiation dose and irradiated area may be important in determining the effects over the LVAD components, but scattered radiation may also play a role. One study reported stability of LVADs after proton beam radiation therapy; specifically five heartware devices were radiated to a cumulative dose of 70Gy. Interrogation of devices showed no changes in function.15 Similarly, another report demonstrated that γ radiation of an LVAD did not change any parameters of the device16 and carefully analyzed the components and materials of a HeartmateII device; they found changes in the driveline materials that were considered not significant enough to compromise lead durability, although no comprehensive fatigue testing was performed. Two of our patients received external radiation, one to the chest and another to the head. Devices were interrogated before and after radiation treatments, and none of them had device malfunction after radiation therapy. Radiofrequency ablation (RFA) of the esophagus has been used for the management of Barret’s esophagus and in some cases of intramucosal carcinoma in combination with endoscopic mucosal resection.17 One of our patients with esophageal cancer received RFA to the esophagus, and he died suddenly few weeks after the treatment. Autopsy determined that the cause of death was device malfunction. Although unlikely, the contribution of RFA to the device malfunction is unclear. Chemotherapy is a cornerstone in the management of most malignancies and results in immunosuppression and susceptibility to infections. Left ventricular assist device driveline infections are common, and up to 19% of patients will have a driveline infection at 1 year of support affecting the overall survival of these patients.18 In addition, pocket infections, blood stream infections,19 and endocarditis have been reported in LVAD-supported patients.20 Thus, patients who are receiving chemotherapy and supported by LVAD may be at increased risk for infections when compared with other cancer patients. In our series, three patients received low intensity chemotherapy. We did not observe any worsening in LVAD-related infections in these patients. It is well known that some chemotherapeutic agents such as Adriamycin can have direct cardiac toxicity in a dose-dependent manner.21 In our series, no patient received antracyclins or other known cardiotoxic chemotherapeutic agents; however, a theoretical question arises, could a LVAD-suppported
612
LOYAGA-RENDON et al.
patient receive a potentially cardiotoxic chemotherapeutic agent? It would be important to point out that in LVAD patients the right ventricle is still unsupported, and thus, chemotherapy could still cause cardiotoxicity with potential hemodynamic significance. Recent history of cancer (
