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Cardiovascular Toxicity Associated
With Cancer Treatment
Pamela Hallquist Viale, RN, MS, CS, ANP, AOCNP®,
and Deanna Sanchez Yamamoto, RN, MS, CS, ANP, AOCNP®
Cardiotoxicity is a well-described and potentially lethal side effect of certain chemotherapeutic agents. Cardiotoxicity is
a broad term used to depict conditions ranging from benign forms of arrhythmias to potentially fatal conditions, such as
myocardial ischemia or infarction and heart failure. Anthracyclines (daunorubicin, doxorubicin, and epirubicin), mitomycin,
and monoclonal antibodies such as trastuzumab have been associated with cardiotoxicities, but other chemotherapeutic
agents, such as fluorouracil, cyclophosphamide, interferons, and interleukin-2 and other targeted agents, also can cause
this side effect. Although several theories exist about the process that leads to cardiotoxicity from some chemotherapeutic
agents, the exact mechanism of action is unknown. Oncology nurses should know the agents associated with cardiotoxicity,
including newer targeted therapy drugs. Knowledge of the potential mechanism of action, as well as the possible reversibility of cardiotoxicity with specific agents, is important.
S
pecific chemotherapy treatments have long been
associated with cardiovascular toxicity in patients
who receive the agents and oncology nurses are
familiar with many of them (Yeh et al., 2004). Additional risk factors can place patients at an increased
threat for toxicity, including the cumulative effects of multiple
chemotherapeutic agents that increase toxicity risk as well as
existing medical conditions that can predispose a patient to
cardiovascular damage. Cancer occurs more frequently in older
adults and, because cardiac disease is more prevalent in this
population, cardiotoxicity associated with cancer therapies are
an increased concern (Chanan-Khan, Srinivasan, & Czuczman,
2004). In addition, many patients now have a prolonged survival
or life expectancy after cancer therapy and clinicians should
view cardiovascular toxicity as a long-term side effect (Meinardi et al., 2000). Serious long-term cardiotoxic effects, such as
congestive heart failure (CHF), have been noted with several
specific types of cancer after therapy, including breast and testicular. According to Pinder, Duan, Goodwin, Hortobagyi, and
Giordano (2007), women aged 66–70 years who received anthracyclines in the adjuvant setting, presented with significantly
higher incidences of CHF over 10 years of follow-up. Therefore,
decisions regarding initial adjuvant therapies should take into
account potential long-term cardiotoxic effects of the treatment
(Partridge, Burstein, & Winer, 2001).
Patients present in many different ways with cardiovascular effects associated with the various agents used in cancer
treatment. Some of the effects include myocardial infarction,
myocarditis or pericarditis, cardiomyopathy, arrhythmias or
changes in cardiac conduction, hypertension, and changes
in electrocardiographic readings (Chanan-Khan et al., 2004).
At a Glance
F Although cardiotoxicity is a well-known side effect of specific
traditional chemotherapy agents, some newer targeted therapy
agents can product cardiotoxic effects as well.
F Laboratory tests, such as electrolytes, blood counts, liver,
thyroid, and B-type natriuretic peptide assay, are used to
determine heart failure in patients on specific chemotherapy
treatments.
F Oncology nurses should be aware of the various risks for
heart failure in patients with cancer and assess and monitor
for early signs and symptoms of toxicity.
Changes can be acute or chronic and may appear years after
therapy is completed (Chanan-Khan et al.).
Oncology nurses should increase their awareness of the cardiac
toxicities that are associated with standard chemotherapeutic
Pamela Hallquist Viale, RN, MS, CS, ANP, AOCNP®, is an oncology nurse
practitioner, consultant, and assistant clinical professor in the Department
of Physiological Nursing at the University of California, San Francisco;
and Deanna Sanchez Yamamoto, RN, MS, CS, ANP, AOCNP®, is a nurse
practitioner in the Department of Rheumatology and Oncology at Santa
Clara Health and Hospital Systems in San Jose, CA. Viale is a speaker and
member of the advisory board for IMER, Bristol-Myers Squibb, Amgen
Inc., and Novartis AG, and a speaker for Meniscus and Merck & Co., Inc.
(Submitted October 2007. Accepted for publication January 2, 2008.)
Digital Object Identifier: 10.1188/08.CJON.627-638
Clinical Journal of Oncology Nursing • Volume 12, Number 4 • Cardiovascular Toxicity Associated With Cancer Treatment
627
agents and targeted therapies, including monoclonal antibodies
and small molecule tyrosine kinase inhibitor (TKI) and multikinase inhibitor (MKI) agents. This article will review the
mechanism of action for cardiotoxicity associated with selected
chemotherapy and targeted therapy agents as well as the implications for nursing in the management of heart failure. Although
radiation therapy also can cause cardiac issues, they will not be
reviewed in this article.
Mechanism of Action for Cardiotoxicity
Associated With Cancer Therapy
Chemotherapy-associated cardiotoxicity may have two markedly different mechanisms of action, depending on the agent
(Safra, 2007). Anthracycline-associated cardiotoxicity, which
causes cumulative damage to the cardiac myocytes leading
to CHF, has been labeled type I chemotherapy-related cardiac
dysfunction (CRCD). The specific damage associated with trastuzumab is type II CRCD (Safra, 2007).
Anthracycline Cardiotoxicity
Cardiotoxicity is a well-known risk of anthracycline agents.
Medications include doxorubicin, daunorubicin, idarubicin,
and epirubicin. Liposomal versions of several of the agents
now exist. Both doxorubicin and daunorubicin have been in
use for several decades to treat breast cancer, leukemia, lymphomas, and a variety of other cancers. The exact mechanism
of action for the myocardial damage is unknown, but it is
believed that free radical-mediated myocyte damage, adrenergic dysfunction, free radical-induced oxidative stress, and
intracellular calcium overload may play a role (Safra, 2007;
Shan, Lincoff, & Young, 1996). In addition, evidence suggests
that the release of cardiotoxic cytokines may contribute to
the toxicity. Although the anthracycline cardiac toxicity may
be labeled type I CRCD (differentiating the damage from trastuzumab), three distinct subtypes of cardiotoxicity related to
this drug class exist (Jones, Swanton, & Ewer, 2006; Shan et
al.) (see Table 1).
Although anthracyclines are valuable agents for treating various cancers, the class of agents has a definitive dose-response
Table 1. Types of Anthracycline Toxicity
Type
Description
Occurring immediately
after therapy
Rare acute or subacute cardiac injury
may manifest as transient arrhythmia,
pericarditis, or myocarditis syndrome.
Chronic cardiotoxicity
More common; early onset of progressive
chronic heart failure or cardiomyopathy
Late-onset cardiotoxicity
Late-onset ventricular dysfunction and
arrythmias occurring years to decades
after treatment ends
Note. Based on information from Jones et al., 2006; Safra, 2007; Shan
et al., 1996.
628
relationship in many of the regimens in which they are used;
therefore, survival and remission rates may be affected if
reduced doses are used (Shan et al., 1996). Chronic cardiotoxicity is dose-limiting and usually occurs as CHF within a year
of treatment (Youssef & Links, 2005). The incidence of CHF
is approximately 3% in patients receiving a cumulative dose
of 400 mg/m2 of doxorubicin, rising to 7% at 550 mg/m2, and
18% at 700 mg/m2 (Youssef & Links). Reports exist of fatal
cardiotoxicity with anthracyclines at cumulative doses less
than 400 mg/m2 when given to patients receiving multiple
chemotherapy agents, such as high-dose methotrexate, bleomycin, cyclophosphamide, dactinomycin, and cisplatin (Watts,
1991). Data suggest that cardiotoxicity may be exacerbated
by combination therapies, and the standard doses considered
to be cumulative limits for anthracyclines may need adjusted
on a case-by-case basis (Watts). Oncology nurses and other
clinicians should monitor cumulative doses of these agents
carefully; once maximum doses are reached, retreatment usually is not possible.
One strategy for reducing anthracycline cardiotoxicity is to
change the infusion method to a continuous administration
instead of a bolus administration (Hortobagyi et al., 1989). Hortobagyi et al. treated 133 patients with doxorubicin by bolus
IV and 141 patients with either a 48- or 96-hour continuous
infusion schedule and found 75% or greater decrease in the
frequency of clinical CHF at cumulative doses less than 450
mg/m2 (p = 0.04). The continuous method of infusion required
a central venous catheter.
Another strategy is to use the pegylated liposomal version of
the drug; however, clinicians must be aware of the indications
for each of the three liposomal anthracycline formulations:
daunorubicin, liposomal doxorubicin, and pegylated liposomal
doxorubicin (Hortobagyi, 1997; Safra, 2003, 2007). Pegylated
liposomal doxorubicin can reduce the risk of cardiotoxicity, allowing for a significantly higher cumulative maximum tolerated
dose (Safra, 2003; Simpson, Herr, & Courville, 2004). The liposomal drug delivery provides for a prolonged circulation time
but a reduced concentration of medication to the cardiac muscle
itself (Simpson et al.). Liposomal daunorubicin has been found
to have a better cardiac safety profile than standard daunorubicin in early studies; however, when patients have received
higher cumulative doses (600–900 mg/m2), cardiotoxicity has
occurred (Gill et al., 1995; Safra, 2003).
Epirubicin has been reported to have less cardiotoxicity than
other anthracycline agents, such as doxorubicin. The cardiac
toxicity associated with epirubicin seems to occur at a higher
cumulative dose (more than 900 mg/m2) compared to 550 mg/
m2 with standard doxorubicin (Safra, 2003). Bonneterre et al.
(2004) reported data from more than eight years of observation
of patients following epirubicin chemotherapy treatment. The
150 patients received either fluorouracil 500 mg/m2, epirubicin 50 mg/m2, and cyclophosphamide 500 mg/m2 (FEC 50)
(n = 65) or fluorouracil 500 mg/m 2 , epirubicin 100 mg/
m 2, and cyclophosphamide 500 mg/m 2 (FEC 100) (n = 85)
for a median follow-up time of 102 months. In the FEC 100
group, left ventricular ejection fraction (LVEF) was less than
50% in five patients (normal LVEF is 50% or more [Aronow,
Ahn, & Kronzon, 1998]), two patients experienced CHF,
and 18 patients had asymptomatic left ventricular dysfunction.
August 2008 • Volume 12, Number 4 • Clinical Journal of Oncology Nursing
One patient suffered left ventricular dysfunction after FEC 50
(Bonneterre et al.). The researchers concluded that the benefits
of treatment with FEC 100 outweighed the risks of therapy
and recommended careful evaluation of cardiac risk factors in
patients selected for therapy (Bonneterre et al.). However, that
conclusion was challenged by Ventura (2005) who cited a lack
of supportive clinical data for the outcome and the potential for
heart failure with either doxorubicin or epirubicin when given
at equimolar doses.
Van Dalen, Michiels, Caron, and Kremer (2006) reviewed
the different anthracyclines with regard to cardiotoxicity
and concluded that no direct evidence suggested any difference between tumor response and survival for doxorubicin
or epirubicin when given at the same dosages. Although a
reduced rate of clinical heart failure may have been seen with
epirubicin-treated patients, the researchers felt that neither
drug was better than the other. However, they did report that
liposomal-encapsulated doxorubicin has a lower rate of clinical and subclinical heart failure for patients receiving the drug
without change in tumor response or survival when compared
to standard doxorubicin (van Dalen et al.). The authors reported
that, in patients with solid tumors, the liposomal preparation
could be favored over traditional anthracyclines; however, more
research was needed.
Other Chemotherapeutic Agents
Associated With Risk of Cardiotoxicity
5-Fluorouracil and Capecitabine
Additional chemotherapy agents have been implicated in
cardiovascular toxicities. The use of 5-fluorouracil (5-FU) is
standard in many treatments for various tumor types, including colorectal cancer. Some researchers list this agent as the
second-most common cause of cardiotoxicity with a reported
incidence of 1.2%–7.6%, although reports exist of greater than
20% incidence with 5-FU (Alter, Herzum, Soufi, Schaefer, &
Maisch, 2006; Chanan-Khan et al., 2004; Pai & Nahata, 2000).
Risk factors for cardiac side effects with 5-FU are not completely
known, but preexisting cardiac disease is believed to play a role
and has been associated with both dose and rate of administration (Yeh et al., 2004) and the presence of preexisting renal
disease (Jones & Ewer, 2006). The mean onset of toxicity is
72 hours after administration (Jones & Ewer). Although lifethreatening cardiotoxicity is rare, it can occur with effects such
as myocardial ischemia and dysrhythmias and changes in electrocardiograph readings (Robben, Pippas, & Moore, 1993; Yeh
et al.). In a study by Canale et al. (2006), 5-FU reportedly caused
acute myocardial infarction during infusion in a patient. Severe
cardiac failure associated with 5-FU also has been reported in
the literature and, after endomyocardial biopsy, the damage
was found to be similar to doxorubicin cardiotoxicity in one
patient (Kuropkat et al., 1999). Capecitabine, as an oral prodrug
of 5-FU, is believed to have the same risk for cardiotoxicity. In a
retrospective study of 1,189 patients by Van Cutsem, Hoff, Blum,
Abt, and Osterwalder (2002), the incidence was 3%, with 0.8%
experiencing grade 3 toxicity (see Table 2).
Cyclophosphamide and Ifosphamide
Cyclophosphamide is a very common alkylating agent given
in different regimens for many cancers and is known to cause
acute cardiac toxicity in smaller doses. Damage from this agent
typically occurs in the myocarditis and pericarditis, and heart
failure can occur. The etiology of the damage is not completely
understood but may be related to direct endothelial injury,
which promotes leakage of plasma proteins and erythrocytes
(Taniguchi, 2005). Patients may experience wall thickening
from the edema, as well as hemorrhage, which combines to
reduce left ventricular diastolic function and causes restrictive cardiomyopathy (Taniguchi). In addition, doses greater
than 1.5 mg/m2 per day are known for an increased risk of
cardiotoxicity, with a reported incidence of 25%–28% at higher
doses (Chanan-Khan et al., 2004; Gottdiener, Appelbaum,
Ferrans, Deisseroth, & Ziegler, 1981; Jones & Ewer, 2006).
The damage seems to be related to the total dose delivered in
a single administration rather than the cumulative dose seen
with anthracyclines (Taniguchi; Yeh et al., 2004). In addition,
patients who have received radiation therapy to the chest or
Table 2. Selected Cardiac General Toxicities From the National Cancer Institute Common Terminology
Criteria for Adverse Events
Grade
Adverse event
1
2
3
4
5
Left ventricular
diastolic function
Asymptomatic diagnostic finding; intervention not indicated
Asymptomatic, intervention indicated
Symptomatic CHF responsive to intervention
Refractory CHF, poorly controlled; intervention such as ventricular assist device or heart transplantation indicated
Death
Left ventricular
systolic dysfunction
Asymptomatic, resting EF < 50%–60%;
SF < 15%–30%
Asymptomatic, resting EF < 40%–50%;
SF < 15%–24%
Symptomatic CHF responsive to intervention; EF <
20%–40%; SF < 15%
Refractory CHF or poorly controlled; EF <
20%; intervention such as ventricular
assist device, ventricular reduction surgery, or heart transplantation indicated
Death
CHF—congestive heart failure; EF—ejection fraction; SF—shortening fraction
Note. Based on information from National Cancer Institute, 2006.
Clinical Journal of Oncology Nursing • Volume 12, Number 4 • Cardiovascular Toxicity Associated With Cancer Treatment
629
had previous treatment with an anthracycline are at higher risk
for cardiotoxicity (Jones & Ewer; Kamezaki, Fukuda, Makino,
& Harada, 2005; Yeh et al.). In one series, patients undergoing
bone marrow transplantation had a 20% incidence of acute
heart failure and a mortality rate of approximately 8% related
to cyclophosphamide (Taniguchi). Ifosphamide, which is
structurally related to cyclophosphamide, also has been linked
to arrhythmias and death in some patients (Chanan-Khan et
al.; Jones & Ewer; Kandylis, Vassilomanolakis, Tsoussis, &
Efremidis, 1989; Quezado et al., 1993; Yeh et al.).
Taxanes
Taxanes, including paclitaxel and docetaxel, can cause cardiotoxicity, with paclitaxel linked to a higher incidence. Although
the cause of cardiotoxicity is not completely known, possible
etiologies include
the use of the glycCardiotoxicity may be exacerbated
erol-polyethylene
glycol-containing
by combination therapies
solution (to proand the standard doses
vide solubi lit y),
considered to be cumulative
agents used in premedication to prelimits for anthracyclines may need
adjusted on a case-by-case basis. vent hypersensitivity reactions, and
the action of the
drug on the microtubules of the cells (Jones & Ewer, 2006). Paclitaxel is reported to have caused sinus bradycardia, heart block,
and premature ventricular contractions (Yeh et al., 2004). The
incidence was approximately 0.5% for grade 4 or 5 toxicities in
one analysis of more than 3,400 patients by Arbuck et al. (1993).
Supraventricular tachycardia and other rhythm abnormalities
also have been observed, including atrial fibrillation (ChananKhan et al., 2004). In early reports, asymptomatic bradycardia
was reported in 29% of patients with ovarian cancer treated in
a phase II study as well as more significant effects, including
heart block and cardiac ischemia, observed in a small group of
patients (Rowinsky et al., 1991). Hypertension, infusion-related
hypotension, and reports of myocardial infarction also have occurred (Chanan-Khan et al.). In one study of epirubicin in combination with paclitaxel, the incidence of CHF was low until a
cumulative epirubicin dose of 990 mg/m2 was reached (Gennari
et al., 1999). The authors concluded that the regimen was safe
even in the adjuvant setting, but the risk increases with doses
exceeding 990 mg/m2 and, if an additional cardiovascular risk
factor is present, reduction of epirubicin may be appropriate
(Gennari et al.). Most of the changes associated with paclitaxel
ended once the agent was discontinued (Jones & Ewer).
The evidence for docetaxel-induced cardiotoxicity is less compelling (Floyd et al., 2005). Shimoyama, Murata, Sumi, Hamazoe,
and Komuro (2001) studied 10 patients with breast cancer and
found that docetaxel significantly increased the serum concentration of brain natriuretic peptide (a protein secreted by the
ventricles of the heart and believed to be a sensitive measure of
CHF) the day after docetaxel administration. After assessment
of left ventricular systolic and diastolic functions, Shimoyama et
al. concluded that, although fractional shortening and ejection
fraction were not affected by docetaxel, the results did suggest
630
that docetaxel induced left ventricular diastolic dysfunction and
an increase in serum brain natriuretic peptide concentration
without increasing preload or afterload.
Miscellaneous Chemotherapy Agents
Cisplatin, mitomycin, and busulfan all have been implicated
in cardiotoxic effects (Gharib & Burnett, 2002; Pai & Nahata,
2000; Yeh et al., 2004). Cisplatin can cause an acute cardiac
syndrome in which patients report chest pain, exhibit increases
in cardiac enzymes, and develop a syndrome where hypertension and left ventricular hypertrophy or myocardial ischemia
may occur many years after treatment (Yeh et al.). The nephrotoxicity associated with cisplatin and the resulting changes in
electrolytes for some patients is believed to intensify cardiac arrhythmias (Berliner et al., 1990; Jones & Ewer, 2006). Meinardi,
Gietema, van der Graaf, et al. (2000) studied the long-term risk
in 87 patients treated with cisplatin-containing chemotherapy
for testicular cancer and found a significantly increased risk for
occurence of cardiac toxicity in the group. The cardiac events
seen were myocardial infarction and angina pectoris with myocardial ischemia. The authors concluded that follow-up and
intervention were important for this patient group (Meinardi,
Gietema, van der Graaf, et al.).
Mitomycin C has long been believed to be cardiotoxic and
that toxicity is dose dependent, occurring at dose levels of 30
mg/m2 or more, and that patients previously or simultaneously
treated with doxorubicin were at greater risk (Verweij, FunkeKupper, Teule, & Pinedo, 1988). Cumulative dosing and effects
related to combined therapies have been reported to contribute
to cardiotoxicity with mitomycin C (Yeh et al., 2004).
Busulfan has been reported to cause pericardial fibrosis in
at least one case report (Terpstra & de Maat, 1989; Yeh et al.,
2004). Bleomycin has been linked to cardiotoxic effects, including pericarditis, acute chest pain syndrome, coronary artery
disease, and myocardial infarction (Floyd et al., 2005).
Mitoxantrone, an anthraquinone, has been reported to cause
toxicity in cardiac cells with doses greater than 160 mg/m2,
putting patients at increased risk for cardiac failure (OSI Oncology, 2007). The incidence of cardiac failure is 2.6%, with a 13%
incidence of subclinical moderate to severe decline in LVEF (OSI
Oncology). Reports of cardiotoxicity with this agent have surfaced in patients receiving the drug for multiple sclerosis (Paul,
Dorr, Wurfel, Vogel, & Zipp, 2007). Etoposide, a podophyllotoxin, has caused cardiac effects such as myocardial infarction
and vasospastic angina in some patients (Floyd et al., 2005).
Other agents that work as microtubule inhibitors include the
vinca alkaloids, which have been reported to cause many different cardiac effects, including hypertension, myocardial infarction, or other vaso-occlusive complications (Floyd et al., 2005).
Targeted Therapy Agents
With Risk of Cardiotoxicity
Targeted therapies, including both monoclonal antibodies
and the small-molecule TKI and MKI agents, are increasingly
used in clinical practice. The agents work differently than
standard chemotherapeutic agents and selectively target key
August 2008 • Volume 12, Number 4 • Clinical Journal of Oncology Nursing
aspects of both intracellular and extracellular function. This
selectivity changes their side-effect profile and, although toxicities exist with these agents, the type of side effects may differ from
traditional chemotherapy (Viale, 2007). However, cardiotoxicity
is a known effect of several of the targeted therapy agents.
Trastuzumab
Trastuzumab has changed treatment for patients with breast
cancer who are HER2/neuregulin-positive. The agent was first
approved by the U.S. Food and Drug Administration (FDA) in
1998 in the metastatic setting and later approved in 2006 in the
adjuvant setting (Genentech, 2008). The HER2 gene is amplified
or the receptor is overexpressed in about 15%–25% of patients
with breast cancer and confers a poorer prognosis and shorter
overall survival for patients (Suter, Cook-Bruns, & Barton, 2004).
The exact mechanism of action for cardiotoxicity is unknown,
but several possible mechanisms exist, with one theory describing the damage as type II CRCD (Safra, 2007). Type II CRCD
involves the endothelial growth factor receptor pathway that
normally maintains cardiac contractility and function. When
blocked by trastuzumab, the pathway is unable to provide
regulation of the growth of cardiomyocytes and interferes with
repair of those cells (Safra, 2007). The pathway and ErbB2 signaling in the cardiac myocytes are critical in the prevention of
dilated cardiomyopathy (Safra, 2007). Although no ligand exists
for HER2, signaling occurs through heteromers with other receptors (Carlson & Perez, 2006). HER2/neuregulin is a critical
component of cardiac development, with HER2 located in the
T-tubule system of cardiomyocytes. However, the exact mechanism of action is unknown (Carlson & Perez). Others have postulated that damage occurs from drug-drug interactions or the
induction of immune-mediated destruction of cardiomyocytes
(Gonzalez-Angulo, Hortobagyi, & Esteva, 2006).
A critical difference between type I and II CRCD is that type
II appears to be mostly reversible, with improvement seen
in cardiac function after discontinuation of treatment (Safra,
2007). Certain factors also increase the risk for cardiotoxicity.
Statistically significant increases were seen as patients aged and
with concurrent use of anthracycline. Other factors are previous
anthracycline use, prior chest wall irradiation, and preexisting
cardiac dysfunction (Floyd et al., 2005).
Although clinically effective as a monotherapy, trastuzumab
combined with chemotherapy enhances its activity (Suter et
al., 2004). Clinical trials with trastuzumab in the metastatic
setting identified cardiac dysfunction as the most significant
adverse event, with a retrospective analysis showing the greatest amount of toxicity in patients who received trastuzumab and
an anthracycline (27%) (Smith, 2001; Suter et al.) compared to
a 7% rate in patients who received anthracycline alone (Smith).
Risk factors for the cardiotoxicity identified in the clinical trials
are similar to the risk factors for patients receiving doxorubicin,
and an independent cardiac review committee concluded that
the two most significant risk factors were age of the patient
(older than 50) and the combination of anthracycline with trastuzumab treatment (Seidman et al., 2002; Suter et al.).
Patients receiving paclitaxel in combination with trastuzumab
also had an increased risk of cardiotoxicity compared to patients on paclitaxel alone (12% versus 1%, respectively) (Smith,
2001). Cardiac dysfunction included asymptomatic decrease
in LVEF. Symptomatic heart failure occurred in 16% of patients
receiving trastuzumab with anthracycline/cyclophosphamide
combinations, which is typical of toxicity associated with trastuzumab (Smith). This cardiac dysfunction was reversible in
most patients with a very low rate of residual heart failure after
treatment, and death occured in less than 1% of patients. The
reversibility is a hallmark of trastuzumab cardiotoxicity compared to the type of damage seen with anthracycline agents
(Jones & Ewer, 2006; Smith). In fact, because of the reversible
nature of cardiotoxicity associated with trastuzumab, reintroduction of the agent after improvement in individual patients
may be possible (Ewer et al., 2005).
With the recent approval of trastuzumab in the adjuvant
setting, the cardiovascular risks are of considerable interest.
Although the drug is well tolerated and has shown tremendous
clinical benefit for HER2/neuregulin-positive patients in both
metastatic and adjuvant settings, the CHF that can occur in
patients receiving the agents is concerning. The results from
the adjuvant trials report that about 5% of all patients treated
with adjuvant trastuzumab, either combined with nonanthracycline chemotherapy or given after all treatment is finished,
will exhibit systolic cardiac dysfunction, with 1% developing
symptomatic CHF (Hayes & Picard, 2006). An analysis by
Suter et al. (2007) of the trastuzumab adjuvant trial showed
that out of 1,693 patients receiving one year of trastuzumab
therapy versus 1,693 on observation alone, the incidence of
drug discontinuation because of cardiac issues was 4.3%. The
researchers concluded that, because of the significant benefit
in disease-free survival of the patients combined with the low
incidence of cardiotoxicity and its reversibility, treatment with
trastuzumab in the adjuvant setting should be considered for
appropriate patients, although the women participating in this
trial were, on average, about 50 years old with 22% having a
history of cardiovascular disease or active cardiovascular disease (Suter et al., 2007).
Because the anthracycline combination with trastuzumab appears to act as a potentiator of cardiotoxicity, the agents should
not be given together (Smith, 2001). Researchers have explored
the use of liposomal doxorubicin in conjunction with trastuzumab to permit concomitant therapy with the two agents.
Theodoulu et al. (2002) studied 39 patients with metastatic
breast cancer and found that one patient had an asymptomatic
decrease in LVEF and one patient experienced CHF. Chia et al.
(2006) studied 30 patients receiving the two agents together and
reported no patients with CHF, but three developed protocoldefined cardiotoxicity, which was considered to be an absolute
decline in LVEF of 15% in an asymptomatic state, despite the
absolute value (Chia et al.). The three patients had received prior
adjuvant anthracyclines.
The Protocol B-31 (a pivotal trial which studied trastuzumab)
recommendations for monitoring guidelines have been used
by many clinicians for managing the drug and its cardiotoxic
effects (see Table 3).
The black box warning for trastuzumab calls for evaluation of
cardiac function prior to and during treatment, and discontinuing
therapy for cardiomyopathy (Genentech, 2008). In addition, the
warning calls for discontinuation of therapy in patients receiving
adjuvant therapy and a strong consideration of discontinuation
of trastuzumab in patients with metastatic breast cancer when a
Clinical Journal of Oncology Nursing • Volume 12, Number 4 • Cardiovascular Toxicity Associated With Cancer Treatment
631
Table 3. Protocol B-31 Rules for Suspension of Trastuzumab
Relationship of
LVEF to the LLN
Decrease of < 10 percentage points
Decrease of
10–15 percentage points
Decrease of
> 15 percentage points
Within radiology facility’s
normal limits
Continue trastuzumab
Continue trastuzumab
Hold trastuzumab and repeat
MUGA scan after four weeks
1–5 percentage points
below the LLN
Continue trastuzumab
Hold trastuzumab and repeat
MUGA scan after four weeks
Hold trastuzumab and repeat
MUGA scan after four weeks
> 6 percentage points
below the LLN
Continue trastuzumab and repeat
MUGA scan after four weeks
Hold trastuzumab and repeat
MUGA scan after four weeks
Hold trastuzumab and repeat
MUGA scan after four weeks
LLN—lower limit of normal; LVEF—left ventricular ejection fraction; MUGA—multigated acquisition
Note. From “Assessment of Cardiac Dysfunction in a Randomized Trial Comparing Doxorubicin and Cyclophosphamide Followed by Paclitaxel, With or
Without Trastuzumab as Adjuvant Therapy in Node-Positive, Human Epidermal Growth Factor Receptor 2–Overexpressing Breast Cancer,” by E. Tan-Chiu,
G. Yothers, E. Romond, C.E. Geyer, M. Ewer, D. Keefe, et al., 2005, Journal of Clinical Oncology, 23(31), p. 7813. Copyright 2005 by the American Society
of Clinical Oncology. Reprinted with permission.
clinically significant decrease in LVEF is seen (Genentech). The
package insert also calls for withholding of the drug after a 16%
or greater absolute decrease in LVEF from pretreatment values or
an LVEF value below institutional limits of normal and a 10% or
greater absolute decrease in LVEF from pretreatment values. Continuing or resuming the drug in patients with cardiac dysfunction
has not been adequately studied.
Additional recommendations are to conduct a thorough
cardiac assessment and evaluation of LVEF by echocardiogram
or multigated acquisition scan prior to starting therapy, with
serial LVEF measurements every three months during and upon
completion of trastuzumab, with repeat LVEF measurements at
four-week intervals when the drug is held for measurable dysfunction (Genentech, 2008). Ongoing measurements of LVEF
should be conducted every six months for at least two years
following drug completion in the adjuvant setting.
Lapatinib
Lapatinib, an oral tyrosine kinase EGFR inhibitor, recently
was approved for use in trastuzumab-treated patients with
metastatic breast cancer with disease progression. Lapatinib
also appears to have activity in patients with metastatic brain
cancer (Moy & Goss, 2006). A study of lapatinib-associated
cardiotoxicity by Perez et al. (2006) found that out of 2,812
patients with a variety of cancers receiving the drug, a decrease
in LVEF was seen in 1.3%, and they were rarely symptomatic.
The cardiotoxicity usually was reversible and did not progress
(Perez et al.). Many patients with nonbreast cancer diagnoses in
the clinical trials had not received prior anthracycline therapy
compared to the participants with breast cancer, which also
could have influenced the low incidence of cardiac failure in
the data analysis (Moy & Goss, 2006).
The current package insert for lapatinib warns that decreases
in LVEF have been reported and that normal LVEF should be confirmed prior to starting therapy with this agent while continuing evaluations during therapy (GlaxoSmithKline, 2007). Dose
modification guidelines for this agent call for lapatinib to be
discontinued in patients with a decreased LVEF that is grade 2 or
greater by National Cancer Institute’s Common Terminology Criteria for Adverse Events and in patients with an LVEF that is less
632
than the institution’s lower limit of normal (GlaxoSmithKline).
The drug may be restarted at a reduced dose of 1,000 mg per day
if the LVEF recovers to normal and the patient is asymptomatic.
Studies are needed to determine further information regarding
lapatinib, although it appears to have a very low incidence of
cardiotoxicity (Moy & Goss, 2007).
Sunitinib
Sunitinib is an oral MKI, approved by the FDA in January
2006 to treat gastrointestinal stromal tumors after progression
or intolerance to imatinib mesylate, and in patients with advanced renal cell carcinoma. Sunitinib targets several receptor
TKI implicated in tumor growth, pathologic angiogenesis, and
metastatic progression of cancer (Rock et al., 2007). A retrospective review by Chu et al. (2007) examined all cardiovascular
events in 75 patients with gastrointestinal stromal tumors who
had participated in a phase I and II trial with sunitinib. The
review showed that 11% had a cardiac event (one patient died
from cardiovascular causes, one had myocardial infarction, and
six developed CHF); 28% of the patients had reductions in their
LVEF of at least 10%, and 19% had reductions of 15% or more.
This agent also caused increases in blood pressure, with 47%
developing hypertension (greater than 150/100 mmHg) (Chu
et al.). The authors hypothesized that the LVEF changes could
be caused by direct toxicity to cardiomyocytes, influenced by
the development of hypertension, and called for close monitoring of both hypertension and LVEF in the patients, particularly
those with a history of coronary artery disease or other cardiac
risk factors (Chu et al.).
Cardiac safety of suntinib in patients with preexisting cardiac
conditions remains unknown in part because patients with
significant history of cardiac issues were excluded from clinical studies. Therefore, patients with a cardiac condition should
be monitored carefully for clinical signs and symptoms of CHF
while receiving sunitinib. A baseline evaluation of the ejection
fraction is recommended for all patients as well as additional
periodic evaluation ejection fraction studies for patients with
known cardiac conditions receiving sunitinib (Pfizer Inc., 2006;
Rock et al., 2007). The time between evaluations should be
determined on a case-by-case basis. Hypertension can develop
August 2008 • Volume 12, Number 4 • Clinical Journal of Oncology Nursing
during therapy and should be monitored closely. The mechanism for this, however, is unclear and may be caused by increasing extracellular volume or decreasing vascular compliance.
Sunitinib-induced hypertension should be managed aggressively
to prevent the long-term effects or the worsening of cardiac
conditions (Wood, 2006).
Sorafenib
Sorafenib, like sunitinib, is an MKI used in the treatment of
advanced renal cell carcinoma, and similar cautionary warnings
about cardiovascular events should apply regarding the development and management of hypertension. Rare but serious lifethreatening or fatal outcomes of cardiac events were reported
with the use of sorafenib and include myocardial ischemia,
myocardial infarction, CHF, hypertensive crisis, and arrhythmia
(Bayer Pharmaceuticals, 2006; Wood, 2006).
Rituximab
Rituximab is a chimeric murine/human monoclonal antibody
directed against the CD20 antigen on B lymphocytes and used
to treat a variety of malignant and nonmalignant conditions.
Rituximab-associated cardiac events are rare, with the greatest
incidence occurring during the first infusion, and may include
infusion-related hypotension, arrhythmia, acute myocardial
infarction, ventricular fibrillation, and cardiogenic shock. The
proposed mechanism for these first infusion events are possibly
related to a cytokine release phenomenon (Chanan-Khan et al.,
2004; Floyd et al., 2005).
Prevention and management of potential cardiac events should
include monitoring patients during and after a rituximab infusion with special attention paid to patients with a known history
of cardiac disease and hypertension. To avoid infusion-related
hypotension, patients should delay taking antihypertensive medications until after the infusion is completed (Chanan-Khan et
al., 2004).
Imatinib Mesylate
Imatinib mesylate is a potent selective inhibitor of the BCRABL tyrosine kinase and is used in the treatment of chronic
myelogenous leukemia, acute lymphoblastic leukemia, myelodysplastic or myeloproliferative diseases, aggressive systemic
mastocytosis, hypereosinophilic syndrome, chronic eosinphilic leukemia, dermatofibrosarcoma protuberans, and gastrointestinal stromal tumor (Novartis Pharmaceuticals, 2006).
Approximately 2%–6% of patients with chronic myelogenous
leukemia receiving imatinib mesylate develop peripheral edema, pleura effusion, pericardial effusion, pulmonary edema,
and ascites (Cohen et al., 2002; Novartis Pharmaceuticals). In
clinical trials that led to FDA approval of imatinib mesylate
for chronic myelogenous leukemia, one patient was reported
to have died with pleural effusion, CHF, and renal failure
(Cohen et al., 2002). The incidence of edema in the trials was
dose- and age-dependent, with the incidence 20% higher for
patients older than age 65 and for those taking a 600 mg per
day dose of imatinib mesylate (Cohen et al., 2002). Therefore,
when Kerkela et al. (2006) reported that 10 patients without
a prior history of heart disease developed severe CHF while
taking imatinib mesylate, changes occurred to the drug label-
ing. The current warning states that any patient with known
heart disease or risk factors for heart failure should be monitored closely and treated should symptoms occur (Kerkela et
al.). In addition, researchers were able to demonstrate that
imatinib mesylate is cardiotoxic as a result of its harmful
effects on cardiomyocytes and transformation of mitochondrial function (Kerkela et al.). Patients at risk for developing
CHF had comorbidities consisting of a prior history of cardiac
disease and advanced age and should be monitored closely for
unexpected rapid weight gain and fluid retention. Any indication of CHF should be investigated immediately and treated
appropriately (Kerkela et al.; Novartis Pharmaceuticals).
Bevacizumab
A recombinant humanized monoclonal antibody, bevacizumab blocks the activity of vascular endothelial growth
factor and is approved as first- and second-line therapy with
5-FU-based chemotherapy for patients with metastatic colon
and lung cancer. A number of cardiovascular adverse effects
have been associated with bevacizumab, including hypertension, CHF, and arterial thromboembolic events. About 14% of
patients treated with bevacizumab while concurrently receiving anthracyclines and 4% of patients with prior anthracycline
exposure treated with bevacizumab developed CHF. Serious
and sometimes fatal cardiac events with bevacizumab use
include arterial thromboembolic events, hypertensive crisis,
and CHF (Cohen, Gootenberg, Keegan, & Pazdur, 2007).
Acute hypertension in as many as 1.7% of patients has been associated with initial or subsequent infusions of bevacizumab
and can last after discontinuation, leading to central nervous
system hemorrhage and, in some cases, fatal encephalopathy
and reversible posterior leukoencephalopathy (Ozcan, Wong,
& Hari, 2006).
Based on evidence that bevacizumab has increased cardiac
toxicity (2% increase in ventricular dysfunction when used
alone, 14% increase in CHF when used concurrently with
anthracyclines, and 4% in patients who had a prior history of
anthracycline exposure), the FDA issued a warning regarding
the risk of stroke, myocardial infarction, angina, reversible posterior leukoencephelopathy, and fatal heart disease (Floyd et al.,
2005; Jones & Ewer, 2006). Prominent risk factors for a cardiac
event include patients being 65 years or older and a prior arterial
thromboembolic event (Floyd et al.). Patients developing uncontrolled hypertension with aggressive medical management
will require temporary suspension and bevacizumab must be
discontinued permanently for hypertension crisis (Genentech,
2007).
Interferons or Interleukins
Interferons are a set of glycoproteins that display antitumor
properties in the treatment of melanoma, hairy cell leukemia,
follicular lymphoma, and AIDS-related Kaposi sarcoma (Skeel
& Khleif, 2003). Interferons can cause flulike symptoms, hypotension or hypertension, tachycardia, and nausea and vomiting two to eight hours after treatment (Yeh et al., 2004). The
cardiotoxicities associated with interferons are ischemia and
infarction, arrhythmias, and cardiomyopathy. Patients with a
previous history of coronary artery disease may be at risk for
Clinical Journal of Oncology Nursing • Volume 12, Number 4 • Cardiovascular Toxicity Associated With Cancer Treatment
633
ischemic changes because the interferon flulike reaction with
fever causes an increased myocardial oxygen demand, but the
exact mechanism is not understood clearly. Risk factors for
interferon-induced cardiotoxicity are not understood clearly
and are not associated with age or dose because toxicity can
occur with low and high daily doses. Only a prior history of
coronary artery disease has been identified as a possible risk
factor to interferon-induced arrhythmia and ischemia (Jones
& Ewer, 2006). If myocardial ischemia develops, the interferon should be discontinued and standard therapy initiated
for myocardial ischemia. Interferon-induced cardiomyopathy
may improve once the drug has been discontinued (Floyd et
al., 2005; Jones & Ewer).
Interleukin-2: Interleukin-2 (IL-2) is a T-cell growth factor with multiple immunomodulating effects and is approved
for the treatment of metastatic renal cell carcinoma, malignant
melanoma, and T-cell lymphoma (Skeel & Khleif, 2003; Yeh et al.,
2004). IL-2 has well-recognized cardiac toxicities, including sinus
tachycardia, arrhythmias, ischemia, or fatal myocardial infarction, without a clearly understood mechanism. From 14%–21% of
patients will have ventricular and supraventricualr arrhythmias.
Supraventricular tachycardia should be treated with standard
antiarrhythmic therapy (Floyd et al., 2005; Jones & Ewer, 2006).
Patients receiving IL-2 commonly develop a capillary leak syndrome associated with vascular permeability and hypotension
(Floyd et al.; Jones & Ewer). High-dose therapy can cause adverse
cardiovascular and hemodynamic effects similar to septic shock
and can lead to vascular leak syndrome (hypotension, edema,
or hypoalbuminemia) and respiratory insufficiency requiring
aggressive medical management with fluid resuscitation, vaspressors, and mechanical ventilation support. The septic shock
symptoms can peak four hours after each dose and worsen with
further treatment (Floyd et al.; Yeh et al.). Establishment of treatment protocols, including premedication with steroids, slowing
or discontinuing infusions with the administration antihistamine,
steroids and epinephrine, fluid resuscitation with infusion reactions, and careful patient selection are necessary to reduce toxicities because, in severe cases, cardiac arrhythmias, myocardial
infarction, cardiomyopathy, and myocarditis can occur (Skeel &
Khleif; Yeh et al.). About 11% of patients can develop thrombotic
events, including deep vein thrombosis, pulmonary embolism,
and arterial thrombosis (Yeh et al.).
Arsenic trioxide: Arsenic trioxide is a novel agent approved in September 2000 by the FDA and currently is used
in various hematologic malignancies. It is associated with
prolongation of the QT interval and potentially serious cardiac
arrhythmia; more than 50% of patients will have electrocardiogram abnormalities (Yeh et al., 2004). Cardiotoxicity associated
with arsenic trioxide usually is acute and occurs during or
immediately after infusion. Hypokalemia or hypomagnesemia
predisposes patients to the cardiotoxic effects of arsenic trioxide. A baseline electrocardiogram should be done before starting therapy to assess the rhythm pattern and QT interval. This
monitoring should be repeated weekly during induction and
biweekly during consolidation. If the QT interval is greater than
500 msec, the patient should be evaluated for the potential risk
versus benefit of further therapy. Prior to each infusion, electrolytes should be checked and corrected if low. Recommended
levels of potassium and magnesium are greater than 4 mEq/l
634
and greater than 1.8 mg/dl, respectively. Patients who develop
cardiac symptoms should be hospitalized with close cardiac
monitoring and correction of electrolytes. Arsenic trioxide usually can be restarted once the QTc interval is less than 460 msec
(Cell Therapeutics, 2000; Floyd et al., 2005).
Nursing Implications for the Diagnosis
and Management of Cardiotoxicity
Oncology nurses should be aware of preexisting cardiovascular disease because it may predispose patients to develop heart
failure or other cardiac issues while being treated with chemotherapeutic agents. For the purpose of this article, the management of heart failure will be the focus because this chronic
condition has the widest implications for nursing care.
Developing Heart Failure
Heart failure is a multifaceted condition that results from
either systolic or diastolic dysfunction impairing ventricular
ejection or filling. The most common cause is coronary artery
disease resulting in myocardial infarction and the loss of myocardial function or ischemic cardiomyopathy (Fadol, 2006;
Macabasco-O’Connell, Rasmusson, & Fiorini, 2006). Patients
can present with dyspnea, orthopnea, paroxysmal nocturnal
dyspnea, activity intolerance, rapid weight gain, fatigue, and
edema. Patients also may complain of upper-right quadrant
pain, loss of appetite and nausea caused by alterations in liver
and gastrointestinal perfusion, and a persistent nonproductive
cough that is worse in a recumbent position (Bashore, Granger,
& Hranitzky, 2007). The symptoms can be mistaken easily for
other conditions, such as cancer progression or side effects of
cancer treatment. To help categorize patients with heart failure,
the New York Heart Association functional classification is used
widely (see Table 4). However, the classification system relies on
patients’ subjective reporting of symptoms. Therefore, some researchers have proposed that biomarker evaluation, specifically
B-type natriuretic peptide assay, and echocardiography should
be used to identify the development of heart failure (Khakoo
et al., 2008).
Patients with symptoms of heart failure should have a thorough history and physical examination. A patient’s medical
history should focus on health conditions, including pulmonary, renal, thyroid, liver, and cardiovascular diseases; uncontrolled hypertension; cardiac arrhythmias; anemia; exposure
to radiation therapy; chemotherapy and targeted therapies;
alcohol use, diabetes; and compliance with medications and
diet. Physical findings specific to heart failure are the presence
of jugular venous distention and a third heart sound, but the
examination will help to identify other causes, such as pleural
effusion, pulmonary embolism, or an infection (e.g., pneumonia) (Bashore et al., 2007; Fadol, 2006; Macabasco-O’Connell
et al., 2006).
Diagnostic Testing and Monitoring for Heart Failure
A number of laboratory and diagnostic studies are used to
confirm heart failutre and consist typically of an electrolyte
panel, a complete blood count, thyroid and liver function,
August 2008 • Volume 12, Number 4 • Clinical Journal of Oncology Nursing
Table 4. New York Heart Association Functional Classification
Functional capacity
Objective assessment
Class I. Patients with cardiac disease but without resulting limitation of physical
activity. Ordinary physical activity does not cause fatigue, palpitation, dyspnea, or
anginal pain.
No objective evidence of cardiovascular disease
Class II. Patients with cardiac disease resulting in slight limitation of physical
activity. They are comfortable at rest. Ordinary physical activity results in fatigue,
palpitation, dyspnea, or anginal pain.
Objective evidence of minimal cardiovascular disease
Class III. Patients with cardiac disease resulting in marked limitation of physical
activity. They are comfortable at rest. Less than ordinary activity causes fatigue,
palpitation, dyspnea, or anginal pain.
Objective evidence of moderately severe cardiovascular disease
Class IV. Patients with cardiac disease resulting in inability to carry on any
physical activity without discomfort. Symptoms of heart failure or the anginal
syndrome may be present even at rest. If any physical activity is undertaken,
discomfort is increased.
Objective evidence of severe cardiovascular disease
Note. From “Classification of Functional Capacity and Objective Assessment,” by American Heart Association, 2006. Retrieved March 18, 2007, from
http://www.americanheart.org/presenter.jhtml?identified=4569. Copyright 2006 by the American Heart Association. Reprinted with permission.
a chest x-ray, electrocardiogram, B-type natriuretic peptide
assay, and echocardiogram or radionuclide ventriculography
(gated blood pool imaging or multigated acquisition scan)
to determine left ventricle function (see Table 5). Cardiac
troponins, creatine phosphokinase, creatine kinase-MB, and
myoglobin, commonly used to determine the extent and
degree of cardiac muscle necrosis, have been proposed as
biomarkers for early detection and diagnosis of chemotherapyinduced cardiac toxicity (Urbanova, Urban, Carter, Maasova,
& Mladosievicova, 2006). However, their use in this setting
remains controversial.
Monitoring a patient with heart failure should consist of assessing signs and symptoms that indicate a worsening of the
condition. Changes in the patient’s functional status or fluid
volume status excess are clues that the patient’s condition is
not responding to medical management and, for that reason, the
patient’s weight should be checked at least three times a week.
Additional reviews of electrolyte, blood urea nitrogen, creatinine, and therapeutic drug levels should be done for patients
on pharmacologic therapy (National Guideline Clearinghouse,
2008). Oncology nurses should monitor weight and appropriate laboratory tests and assess for the development of edema or
swelling of the lower limbs.
Heart Failure Treatment
Treatment should be initiated once a heart failure diagnosis
has been established. No established guidelines exist regarding
chemotherapy or targeted therapy modifications. A consultation with a cardiologist should be considered. Patients should
be encouraged to discontinue cigarette smoking and alcohol
use and maintain an optimal blood pressure and weight while
making dietary changes. Patients with mild to moderate heart
failure should be encouraged to participate in regular physical
activities such as walking to improve functional status, and a
formal cardiac rehabilitation should be considered for patients
who are dyspneic at rest.
Pharmacologic management of heart failure is dependent
on the presenting signs and symptoms. Diuretic therapy is effective in relieving symptoms such as dyspnea and edema in
patients with moderate to severe CHF (Bashore et al., 2007;
Macabasco-O’Connell et al., 2006). High doses of diuretics can
lead to hypotension and hypokalemia from volume depletion.
Angiotensin-converting enzyme inhibitors are used to reduce
mortality and improve symptoms, quality of life, and exercise
tolerance. In addition, beta blockers reduce mortality in patients
with heart failure and reduced ejection fraction (Bashore et
al.).
Angiotensin receptor blockers can be used in patients who
are intolerant of angiotensin-converting enzyme inhibitors and
present with cough, rash, or angioneurotic edema. Heart failure
also can be worsened by nonsteroidal anti-inflammatory drugs,
cyclooxygenase inhibitors, calcium channel blockers, antiarrhythmics except for digoxin, beta blockers, and amiodarone
(Bashore et al., 2007; Macabasco-O’Connell et al., 2006).
Implications for Nursing
Oncology nurses should be aware that multiple reasons exist
as to why patients with cancer are at risk for developing heart
failure. Patients must be assessed for risk factors, such as prior
or current use of cardiotoxic agents (anthracyclines) and other
chemotherapeutic and targeted therapies, current or past history of radiation therapy to the chest, or preexisting cardiovascular disease. At-risk patients should be monitored for signs and
symptoms of early heart failure and, when appropriate, undergo
monitoring or diagnostic studies. Basic monitoring procedures,
such as vital signs and weight measurements, are important
tools that should not be overlooked or undervalued. Some chemotherapy and targeted therapy agents, such as anthracyclines
and trastuzumab, require baseline and ongoing cardiovascular
assessment to continue safe administration of the therapy. Oncology nurses have a duty to not only administer chemotherapy
Clinical Journal of Oncology Nursing • Volume 12, Number 4 • Cardiovascular Toxicity Associated With Cancer Treatment
635
Table 5. Diagnostic Tests to Determine Heart Failure Versus Other Causes
Test
Diagnostic significance
Electrolyte panel
Assesses renal function and identifies electrolyte abnormalities causing dysrhythmias
Complete blood count
Identifies anemia and infection
Thyroid function
Excludes thyrotoxicosis or myxedema
Liver function
Detects elevated levels from fluid overload, which may cause liver congestion
Chest x-ray
Identifies pneumonia, effusion, pneumothorax, new metastatic lesions, and cardiomegaly
Electrocardiogram
Not specific for heart failure, but identifies arrhythmia, myocardial infraction, and conduction abnormality
B-type natriuretic
peptide assaya
Detects elevated results, which are sensitive in symptomatic patients with heart failure; not as accurate in older patients or
in patients with chronic obstructive pulmonary disease, cirrhosis, or renal failure
Echocardiogram
Determines heart size and chamber function; identifies pericardial effusion, valvular defects, ventricular thrombus, left ventricular hypertrophy, and evidence of a previous myocardial infarction; limited results seen in patients with severe pulmonary
disease
Multigated acquisition
scanb
Measures left ventricle function with greater consistency and accuracy than an echocardiogram; virtually identical in determining cardiac functional status as echocardiogram; commonly used to screen and monitor patients receiving chemotherapy.
Level less than 100 pg/ml, no heart failure; 100–300 pg/ml, heart failure is present; more than 300 pg/ml, mild heart failure; above 600 pg/ml, moderate heart failure; and 900 pg/ml or higher, severe heart failure
a
b
Normal ejection fraction is 50% or higher.
Note. Based on information from Aronow et al., 1998; Bashore et al., 2007; Cleveland Clinic Heart and Vascular Institute, 2008; Fadol, 2006; Mininni &
Tasota, 2003.
safely but to be ever vigilant regarding the long-term sequelae
of patients exposed to cardiotoxic agents.
Conclusion
A number of cancer treatments can cause cardiotoxicities that
range from minor events to life-threatening conditions. Some
treatments require no more than discontinuation of the agent
to reverse the cardiotoxic event, whereas others need careful
selection of patients and ongoing monitoring. As the population
of the United States ages, more patients needing cancer treatment will have comorbidities. The comorbidities, particularly
heart disease, may put patients at increased risk for cardiotoxic
events. Oncology nurses should be aware of the cardiovascular
risks of specific agents, their monitoring guidelines, and signs
and symptoms of cardiovascular toxicity.
Author Contact: Pamela Hallquist Viale, RN, MS, CS, ANP, AOCNP®, can
be reached at [email protected], with copy to editor at CJONEditor@
ons.org.
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August 2008 • Volume 12, Number 4 • Clinical Journal of Oncology Nursing