| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Original Research |
1 Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1270 York
Ave., New York, NY 10021.
2 Department of Radiology, New York-Presbyterian Hospital, New York, NY.
3 Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New
York, NY.
4 Department of Cardiology, Memorial Sloan-Kettering Cancer Center, New York,
NY.
5 Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York,
NY.
Received September 6, 2007;
accepted after revision January 14, 2008.
Address correspondence to J. Rademaker
(rademakj{at}mskcc.org).
Abstract
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
MATERIALS AND METHODS. We evaluated nine consecutive patients, age range 35–60 years, who had been treated for Hodgkin's lymphoma by radiation therapy between the ages of 11 and 27 years. The total mediastinal dose ranged from 34 to 45 Gy. All patients were evaluated with 64-MDCT with calcium scoring followed by CT angiography of the coronary arteries. Imaging findings and clinical follow-up were analyzed.
RESULTS. Eight of nine patients had coronary artery disease. CT showed long segments of diffuse disease; areas of stenosis from soft plaque; and calcification in the proximal right coronary, left anterior descending, and left circumflex arteries. Calcium scores were significantly higher than in other patients of this age group. Additional tests, including selective coronary angiography, were necessary in patients with diffuse disease with calcifications. CT evaluation led to bypass surgery and angioplasty in two patients.
CONCLUSION. Coronary CT angiography and calcium scores are useful tools for evaluation of irradiation-related coronary artery disease. Complementary tests might be necessary in selected patients. Prospective larger studies are needed to better define the role of coronary CT angiography and calcium scores and to establish an algorithm for evaluation and treatment of these patients.
Keywords: calcium score • coronary artery disease • coronary CT angiography • Hodgkin's disease • mantle field radiation
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
A recent study by Heidenreich et al.
[8] used stress
echocardiography and nuclear scintigraphy in 294 asymptomatic patients treated
with mediastinal irradiation. Sixty-three patients (21%) of their Hodgkin's
lymphoma survivors had an abnormal test. Twenty-two of these 63 patients
showed 
50% stenosis at angiography. Because of the known cardiovascular
risks, more rigorous surveillance has been advocated in this population
[8].
The purpose of our study was to evaluate the coronary CT angiography findings and calcium scores in asymptomatic patients who were previously treated with mediastinal irradiation for Hodgkin's lymphoma to correlate these findings with clinical data and to assess the clinical value of coronary CT angiography and calcium scores to the process of clinical decision making. All of the patients in our study had a history of high-dose irradiation in childhood or young adulthood.
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Patient Characteristics
Nine patients who had previously been treated with mediastinal irradiation
for Hodgkin's lymphoma (three women, six men; median age, 45.3 years; age
range, 35–60 years) were included in this study. Radiation dose and time
since radiation therapy are shown in Table
1. All patients were referred from the Memorial Sloan-Kettering
Cancer Center Program for Adult Survivors of Pediatric Cancer to screen for
coronary artery disease. Six of the nine patients had their mediastinal
radiation therapy at another institution. All patients were asymptomatic with
respect to symptoms of ischemic coronary artery disease. Demographic
information and cardiac risk factors are summarized in
Table 1. None of the patients
had ECG findings to suggest acute or previous myocardial infarction. Seven of
the nine patients had one or more risk factors such as hyper tension
(Table 1). Four patients had a
history of hypertension well controlled with medication. Four patients had a
history of hypercholester olemia, one treated with a statin, one other with
diet and exercise (well controlled). One of the patients with a history of
hypertension also had non-insulin-dependent diabetes mellitus diagnos ed at
the age of 40 years, which was well controlled.
|
Patient Preparation
An oral β-blocker (50 or 100 mg of metoprolol) was administered in
four of the nine patients to decrease the heart rate. Beta blockade was not
used in five of the nine patients because of an incomplete left bundle branch
block, chronic obstructive pulmonary disease (COPD), or a relatively low
systolic blood pressure (systolic blood pressure less than 100 mm Hg). Of the
four patients who received the oral β-blocker, two underwent limited
studies due to a sudden increase in heart rate during the actual CT, and in
these patients, a repeat examination was performed later. On the basis of our
experience, we chose to slowly reduce higher heart rates with oral
β-blockers over a period of 1 week before the repeat examination in these
patients.
Image Acquisition Parameters
A combined coronary CT angiography with calcium score was performed in all
patients in accordance with the current understanding of most radiology
centers that both examinations are part of the cardiac CT examination. All
studies were performed on a 64-MDCT scanner (LightSpeed 64 VCT, GE Healthcare)
with an individual detector width of 0.625 mm. First an unenhanced sequence
with prospective ECG gating was performed to assess the volumetric and
Agatston coronary calcium scores (SmartScore [GE Healthcare]; 120 kV;
440–500 mA; rotation time, 0.35 second). Sub sequent coronary CT angio
graphy with retro spective ECG gating was performed immediately after
unenhanced CT. The anatomic coverage extended from the inferior edge of the
aortic arch to the inferior aspect of the heart. The gantry rotation time was
350 milli seconds. The scanning protocol included a tube voltage of 120 kV and
a current of up to 750 mAs using automatic tube–current modulation. In
each patient, the pitch (table movement per rotation/slice collimation) was
adjusted to the patient's heart rate (around 0.2 in most of the patients). The
contrast transit time was determined with a test bolus of 20 mL of iodixanol
(Visipaque 320, GE Healthcare) at 4 or 3.5 mL/s followed by a 20-mL normal
saline flush at the same injection rate. The injection rate was assessed by
our CT nurse, who supervises all power injections of contrast mater ial.
Subsequently, for the coronary CT angio graphy, 80 mL of Visipaque was
injected at 3.5–4 mL/s followed by a 50-mL normal saline flush at the
same injection rate.
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
|
|
|
|
|
Six of the nine patients had calcium scores above the 90th percentile for their age and sex group. In two of these patients, the calcium scores were > 800. The remaining three of the nine patients had calcium scores in the 25th, 50th, and 75th percentiles for their age and sex. Four of the nine patients showed the mean calcium scores of patients 15 years older [9, 10]. Additional findings in the two patients with the most severe disease included indistinct vessel walls and a relative paucity of diagonal branches when compared with a typical coronary system. The patients with the lowest radiation dose and the shortest interval since radiation therapy (patients 6 and 8, respectively) had minimal or no findings of coronary artery disease.
Clinical Follow-Up
Table 2 summarizes the
clinical follow-up and management of the patients. Five patients did not
require additional tests after coronary CT angiography and calcium score. It
should be noted that this included two patients (patients 5 and 7) with
elevated calcium scores (> 400) who would not have been candidates for
aggressive treatment options. Four patients required additional tests to
analyze the hemodynamic significance of the CT findings.
Two patients were referred for coronary angiography (patients 1 and 4). One patient showed > 75% stenosis in the left main coronary artery (LM) and LAD, which led to two-vessel coronary artery bypass surgery. The second patient was found to have a high-grade LCX stenosis and was treated with angioplasty. These stenoses were, even in retrospect, difficult to visualize because of the blooming artifact from coronary calcification. These two patients also had CT angiographic evidence of diffuse coronary artery dis ease with noncalcified and calcified plaques and wall irregularities (Fig. 3), which were angiographically proven to be without stenosis. These finding suggest that these vessels underwent eccentric remodeling [11].
|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The study by Heidenreich et al.
[8] used stress
echocardiography and nuclear scintigraphy to evaluate 294 asymptomatic
patients treated with mediastinal irradiation. Twenty-two of their 63 patients
with a positive stress test showed 50% stenosis at coronary angiography.
Their study design called for coronary angiography only in patients with a
positive stress test. This approach does not identify patients with coronary
artery disease and a negative stress test, who might also benefit from medical
interventions such as risk profile modification. Our approach had a higher
sensitivity for the detection of coronary artery disease, and eight of nine
patients were found to have evidence of coronary artery disease. Three of our
nine patients were subsequently found to have a positive stress test (patient
4), angiographically proven significant LCX stenosis (patient 1), or CT
angiographically proven 75% coronary stenosis (patient 5) (Fig.
1A,
1B). We observed a higher
incidence of severe coronary artery disease than was reported in the
Heidenreich et al. study, possibly because of a bias in patient selection. All
of our patients were relatively young at the time of radiation therapy, and
they received relatively high radiation doses, thus increasing the likelihood
that advanced disease would be found.
Our pilot study shows the potential use of combined coronary CT angiography with calcium scores in this patient group. Evaluation of a larger group will provide a better view of the spectrum of findings and a stronger evaluation of the use of coronary CT angiography. There might be patients with minor or no coronary artery disease who received higher doses of radiation and vice versa. We do not advocate that combined coronary CT angiography and calcium score examination replace other cardiac tests. In almost half of our patients, additional tests were required. We used the calcium score to assess the calcified plaque burden and agree with the views expressed in the recent review by Leontiev and Dubinsky [20] regarding the limitations of the calcium score for clinical decision making.
The combination of coronary CT angiography and calcium score has several diagnostic advantages in comparison with other approaches. Coronary CT angiography has higher sensitivity in disease detection. This is a major advantage that would be lost if patients with prior mediastinal irradiation were evaluated only by a stress test and the calcium score. Evaluation with a stress test but without coronary CT angiography and without the calcium score would have underdiagnosed a number of patients in our study who had coronary artery disease but no hemodynamically significant stenosis. It is also import to remember that stress tests produce a significant number of false-positive or false-negative results. Measurement of the calcium score alone probably would not allow identification of patients who need to undergo further functional testing. Patients with low or moderate calcium scores might have significant coronary artery disease, as in the case of one of our patients (patient 4). In another patient (patient 6), we identified a 40% stenosis that required follow-up. As shown in Figure 1A (patient 5), coronary CT angiography also added significantly to the understanding of the condition of a patient with a high calcium score.
The extent of coronary artery disease after mediastinal irradiation most likely depends on several factors, including the radiation dose, the patient's age at the time of radiation, the radiation field, and the time interval after the radiation, as well as on the presence of additional risk factors. Future studies are required to evaluate the influence of these factors. The number of evidence-based studies about risk, prognosis, and treatments for radiation-related coronary artery disease is limited. Recent studies have documented an increased incidence of cardiovascular events approximately 19 years after the radiation therapy [21]. Among patients undergoing cardiac surgery after thoracic irradiation, hospital deaths and respiratory complications were higher after more extensive radiation exposure [22], and routine use of the internal mammary artery for cardiac revascularization may not be possible [23].
The relative risk for acute myocardial infarction was highest when patients were irradiated before they were 20 years old and decreased with increasing age at treatment [7]. This raises the question of when premature arteriosclerotic disease after mediastinal irradiation starts to develop and when screening for disease should begin. Concern about the possibility of asymptomatic disease should definitely increase 15–20 years after the irradiation. Coexisting risk factors such as hypercholesterolemia, diabetes, or arterial hypertension that are suitable for risk modulation might lead to earlier evaluations. It should be noted that patients with severe disease, such as those in our group, might be asymptomatic because of radiation-related nerve impairment or reduced exercise tolerance.
Hodgkin's lymphoma has a bimodal incidence curve, the first being young adulthood (age range, 15–35 years) and the second being in those more than 55 years old. The results of our study refer to younger patients who were treated in the 1970s, 1980s, and 1990s with relatively high mediastinal radiation doses. These survivors of Hodgkin's lymphoma face significantly increased risk of premature coronary artery disease, myocardial infarction, and cardiovascular-related mortality. In a British cohort of 7,003 Hodgkin's lymphoma survivors with an average of 11.2 years of follow-up, the standardized mortality ratio secondary to myocardial infarction was 3.2 for those who were treated with mediastinal irradiation [3]. The absolute excess risk was 125.8 per 100,000 person-years.
Aleman and colleagues [21] reported that by 30 years after mediastinal irradiation, the cumulative incidence of myocardial infarction was 12.9%. They reported a standardized incidence ratio of 3.6 for myocardial infarction, with 357 excess cases per 100,000 person-years. Traditional risk factors (smoking, hypercholesterolemia, diabetes) increased risk. In the Netherlands, Reinders et al. [12] reported an actuarial risk of symptomatic ischemic coronary artery disease of 21.2% by 20 years after irradiation in Hodgkin's lymphoma survivors treated with moderate-dose mediastinal irradiation (median, 37.2 Gy). On the basis of this evidence and because the risk of coronary artery disease in these patients may be reduced with aggressive intervention and follow-up, screening for asymptomatic coronary artery disease in Hodgkin's lymphoma survivors has been recommended by experts in the field [3–5, 7, 12, 21].
The standard Hodgkin's lymphoma therapy, introduced in the 1960s, administered 40–44 Gy in 2- to 2.2-Gy fractions and often was weighted anteriorly. Historically, the mantle radiation dose favored the anterior mediastinum to avoid toxicity to the esophagus and spinal cord, and in addition, the wing effect resulted in an increased dose at the edge of the field [24]. In the 1980s and 1990s, with the introduction of a combined-technique approach, the doses were reduced from 40 to 30 and even 20 Gy and the field of radiation diminished in volume. Because of advances in imaging, the advent of radiation planning techniques, and the availability of a new generation of radiation equipment, the radiation field volume has markedly decreased, resulting in decreased exposure of the cardiac structure to radiation. The total dose in our patients ranged from 34 to 45 Gy, with the majority of patients receiving more than 40 Gy. Seven of nine patients were treated with radiation therapy before or in 1980, and this explains the relatively high doses in our patient group. In accordance with this radiation distribution, the CT findings of proximal vessel coronary artery disease suggest a correlation with the traditional radiation field in which the inferior and posterior borders of the heart were excluded.
We encountered a few important limitations in performing these coronary CT angiography examinations of Hodgkin's lymphoma survivors. Image quality in coronary CT angiography depends on the patient's heart rate, and coronary CT angiography might therefore be of limited value in certain patients. Patients with prior mediastinal radiation therapy often have vasovagal dysfunction from radiation-related vagal damage. These patients frequently tend to have higher resting heart rates (often > 100 beats per minute), which are difficult or even dangerous to reduce with a single dose of oral or IV β-blockers at the time of CT. Our practice is to slowly reduce the heart rate of patients with vagal dysfunction by administering oral β-blockers over a period of 1 week (for example, an adult-sized patient without contraindications to β-blockers receives metoprolol 25 mg twice a day for 5 days before CT and then 50 mg orally the morning of the test) and then slowly taper the dose over another week after CT. Furthermore, patients with prior mediastinal irradiation often have treatment-associated pulmonary fibrosis and COPD, relatively low systolic blood pressure, or bundle branch block, which also limits the use of β-blockers for optimization of the heart rate.
Coronary CT angiography is probably most difficult to interpret in patients with coronary calcifications or diffuse disease with calcifications, making it difficult to visualize the adjacent vessel lumen [25]. Either underestimation or overestimation of disease should always be considered in patients with diffuse coronary disease and calcifications. It continues to be our policy to pursue complementary tests to evaluate for inducible ischemia in patients who are candidates for bypass surgery or angioplasty. Four of nine patients in our series required additional tests to analyze the hemodynamic significance of the CT findings.
Prospective larger studies are needed to better define the role of coronary CT angiography and calcium scores in the monitoring of patients with prior mediastinal irradiation and to establish an algorithm for evaluation and treatment of these patients. Larger studies would also allow more detailed analysis of the importance of factors such as radiation dose, patient age at the time of irradiation, radiation field, and time interval since irradiation, all of which contribute to the extent of coronary artery disease.
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
