Early Detection Of Anthracycline-induced Cardiotoxicity Research Articles

Assessment of Native Myocardial T1 Mapping for Early Detection of Anthracycline-Induced Cardiotoxicity in Patients with Cancer: a Systematic Review and Meta-analysis

Anthracycline antibiotic is one of the most effective anti-tumor drugs used to manage certain types of breast cancers, lymphomas, and leukemias. However, anthracyclines induce a dose-dependent cardiotoxicity that may progress to heart failure. Thus, using a sensitive predictor of early cardiac dysfunction in patients treated with anthracyclines can help detect subclinical cardiac dysfunction early and help initiate interventions to protect these patients. Among parameters of myocardial measure, cardiac magnetic resonance (CMR)-measured native myocardial T1 mapping is considered a sensitive and accurate quantitative measure of early subclinical cardiac changes, particularly cardiac inflammation and fibrosis. However, to understand the quality and the validity of the current evidence supporting the use of these measures in patients treated with anthracyclines, we aimed to conduct a systematic review of clinical studies of this measure to detect early myocardial changes in cancer patients treated with anthracyclines. The primary outcome was the level of native T1 mapping. We performed fixed-effects meta-analyses and assessed certainty in effect estimates. Of the 1780 publications reviewed (till 2022), 23 were retrieved, and 9 articles met the inclusion criteria. Our study showed that exposure to anthracycline was associated with a significant elevation of native myocardial T1 mapping from baseline (95% CI 0.1121 to 0.5802; p = 0.0037) as well as compared to healthy control patients (95% CI 0.2925 to 0.7448; p < 0.0001). No significant publication bias was noted on the assessment of the funnel plot and Egger’s test. According to the Q test, there was no significant heterogeneity in the included studies (I2 = 0.0000% versus healthy controls and I2 = 14.0666% versus baseline). Overall, our study suggests that native myocardial T1 mapping is useful for detecting anthracycline-induced cardiotoxicity in patients with cancer.

Early detection of anthracycline-induced cardiotoxicity using [68Ga]Ga-FAPI-04 imaging.

Anthracycline-induced cardiotoxicity (AIC), whose major manifestation is diffuse myocardial fibrosis, is an important clinical problem in cancer therapy. Therefore, early identification and treatment are clinically important. This study aims to explore the feasibility of using 68Ga-labelled fibroblast activation protein (FAP) inhibitor ([68Ga]Ga-FAPI) positron emission tomography/computed tomography (PET/CT) for the early identification of the fibrotic process and guidance of antifibrosis therapy in AIC. An AIC rat model was induced by the intravascular administration of doxorubicin (DOX) once per week for 1, 2, 3 and 6weeks (2.5mg/kg/injection, groups 1-4), whereas intravascular saline was administered to control rats. Experimental and control groups (n = 4) underwent [68Ga]Ga-FAPI PET/CT following disease induction. Groups 5 and 6 received DOX injections for 3 and 6weeks, treated with angiotensin-converting enzyme (ACE) inhibitor starting at 3weeks, treated with enalapril (20mg/kg, gastric gavage) daily and underwent echocardiography and [68Ga]Ga-FAPI PET/CT at 3weeks after treatment. Rat hearts were subjected to haematoxylin and eosin staining, FAP immunohistochemistry, Sirius red staining and Masson's trichrome staining to investigate the pathological changes and deposition of collagen fibres. Rat blood was sampled weekly for the enzyme-linked immunosorbent assay of various markers of myocardial injury, such as plasma cardiac troponin I, B-type natriuretic peptide and angiotensin II. [68Ga]Ga-FAPI-04 uptake by the heart was significantly higher in the cardiotoxicity group than in the control group at weeks 3 (SUVmax: 1.21 ± 0.23 vs 0.67 ± 0.01, P < 0.05) and 6 (SUVmax: 1.48 ± 0.28 vs 0.67 ± 0.08, P < 0.001), whereas left ventricle ejection fraction (LVEF) did not significantly differ between normal and AIC rats at week 3. FAP+ expression began to increase starting at week 3, before irreversible fibrotic changes were detected, until week 6. After 3weeks of enalapril treatment, [68Ga]Ga-FAPI-04 accumulation decreased in groups 5 and 6 (SUVmax decreased from 1.21 ± 0.23 to 0.77 ± 0.08 and 1.48 ± 0.28 to 1.09 ± 1.06, P < 0.05). Cardiac function was preserved (LVEF was 75.7% ± 7.38% in group 3 vs 74.5% ± 2.45% in group 5, P > 0.05) and improved (LVEF increased from 51.6% ± 9.03% in group 4 to 65.2% ± 4.27% in group 6, P < 0.05), and myocardial fibrosis attenuated (from 6.5% ± 1.2% in group 4 to 4.31% ± 0.37% in group 6, P < 0.01). [68Ga]Ga-FAPI PET/CT can be used for the early detection of active myocardial fibrosis in AIC and the evaluation of the efficacy of therapeutic interventions. Early treatment guided by [68Ga]Ga-FAPI PET/CT may reduce anthracycline-induced myocardial injury and improve heart function.

14,15-Dihydroxyeicosatrienoic acid, a soluble epoxide hydrolase metabolite in blood, is a predictor of anthracycline-induced cardiotoxicity – a hypothesis generating study

BackgroundEarly identification of patients susceptible to chemotherapy-induced cardiotoxicity could lead to targeted treatment to reduce cardiac dysfunction. Rats treated with doxorubicin (DOX), a chemotherapeutic agent, have increased cardiac expression of 14,15-dihydroxyeicosatrienoic acid (14,15-DHET), a bioactive lipid implicated in hypertension and coronary artery disease. However, the utility of 14,15-DHET as plasma biomarkers was not defined. The aim of this study is to investigate if levels of 14,15-DHET are an early blood biomarker to predict the subsequent occurrence of cardiotoxicity in cancer patients after chemotherapy.MethodsH9c2 rat cardiomyocytes were treated with DOX (1 μM) for 2 h and levels of 14,15-DHET in cell media was quantified at 2, 6 or 24 h in media after DOX treatment. Similarly, female Sprague–Dawley rats were treated with DOX for two weeks and levels of 14,15-DHET was assessed in plasma at 48 h and 2 weeks after DOX treatment. Changes in brain natriuretic peptide (BNP) mRNA, an early cardiac hypertrophy process, were determined in the H9c2 cells and rat cardiac tissue. Results were confirmed in human subjects by assessment of levels of 14,15-DHET in plasma of breast cancer patients before and after DOX treatment and left ventricular ejection fraction (LVEF), a clinical marker of cardiotoxicity.ResultsLevels of 14,15-DHET in cell media and rat plasma increased ~ 3-fold and was accompanied with increase in BNP mRNA in H9c2 cells and rat cardiac tissue after DOX treatment. In matched plasma samples from breast cancer patients, levels of 14,15-DHET were increased in patients that developed cardiotoxicity at 3 months before occurrence of LVEF decrease.ConclusionsTogether, these results indicate that levels of 14,15-DHET are elevated prior to major changes in cardiac structure and function after exposure to anthracyclines. Increased levels of 14,15-DHET in plasma may be an important clinical biomarker for early detection of anthracycline-induced cardiotoxicity in cancer patients.

An image processing tool for the detection of anthracycline-induced cardiotoxicity by evaluating the myocardial metabolic activity in [18F]FDG PET/CT

PurposeChemotherapy-induced cardiotoxicity is one of the main complications during and after cancer treatment. While echocardiography is the most used technique in clinical practice to evaluate left ventricular (LV) dysfunction, a multimodal approach is preferred for the early detection of anthracycline-induced cardiotoxicity. In this paper, an image processing tool allowing the qualitative and quantitative analysis of myocardial metabolic activity by [18F]fluorodeoxyglucose (FDG) positron emission tomography computed tomography (PET/CT) images, acquired routinely during and after cancer treatment, is presented.MethodsThe methodology is based on cardiac single photon emission computed tomography image processing protocols used in clinical practice. LV polar maps are created, and quantitative regional values are calculated. The tool was validated in a study group of 24 patients with Hodgkin or non-Hodgkin lymphoma (HL and NHL, respectively) treated with anthracyclines. Staging, interim and end-of-treatment [18F]FDG PET/CT images were acquired and the presented tool was used to extract the quantitative metrics of LV metabolic activity.ResultsResults show an overall increase of metabolic activity in the interim PET image acquired while on treatment compared to staging PET, which then decreased in the end-of-treatment scan. Positive correlation coefficients between staging and interim scans, and negative correlation coefficients between interim and end-of-treatment scans also support this finding. Metabolic changes occur predominantly in the septal region.ConclusionThe proposed methodology and presented software solution provides the capability to assess quantitatively myocardial metabolism acquired by routine [18F]FDG PET/CT scanning during cancer treatment for evaluating anthracycline-induced cardiotoxicity. The [18F]FDG PET/CT septal-lateral uptake ratio is proposed as a new quantitative measure of myocardial metabolism.

Study of some clinical parameters and cardiac biomarkers for early diagnosis of anthracycline-induced cardiotoxicity in child

Cardiomyopathy induced by the anthracycline cardiotoxicity aggravates the prognosis of the underlying disease and requires an early diagnosis even before the clinical manifestations of myocardial infarction. Establishing the utility of QT and QTc interval dispersion research and cardiac biomarker values, natriuretic peptide B (BNP), for the early detection of anthracycline-induced cardiotoxicity in children with haematological malignancies. Patients - 46 children (aged 2 months to 18 years) treated with anthracyclines for haematological malignancies (leukemias, malignant lymphomas). Control group: 20 apparently healthy children without a history of cardiovascular disease. Patients and the control group were evaluated by clinical examination, 12-channel ECG (3 consecutive QT/QTc interval dispersion), echocardiography (Echo), BNP plasma concentrations. Changes in the parameters investigated: (1) Increased QT/QTc intervals 73% of cases, particularly in patients with a combined anthracycline dose > 250 mg/m 2 and in patients with Echo modifications induced by anthracycline cardiotoxicity, even just a diastolic dysfunction of VS. QT interval average: 80 milliseconds in patients/40 milliseconds in controls; QTc median dispersion: 87,103 milliseconds in patients vs. 55.47 milliseconds in controls; (2) Elevated BNP in 45.7% of patients: mean baseline 89 ng/mL to 240 ng/mL Biological changes were correlated with the presence of clinical signs, echo-induced cardiotoxicity changes and increased QT/QTc interval dispersion. Elevated BNP and QT/QTc intervals in children treated with anthracyclines correlate positively with the occurrence of severe cardiotoxicity manifestations, represent a useful indicator for cardiotoxicity. Changes in these parameters occurred early in cardiotoxicity-induced echo changes and systematic monitoring of these parameters during and after cytostatic treatment is required.

In Vivo Reactive Oxygen Species Detection With a Novel Positron Emission Tomography Tracer, 18F-DHMT, Allows for Early Detection of Anthracycline-Induced Cardiotoxicity in Rodents

Reactive oxygen species (ROS) are involved in doxorubicin-induced cardiotoxicity. The authors investigated the efficacy of 18F-DHMT, a marker of ROS, for early detection of doxorubicin-induced cardiotoxicity in rats. Echocardiography was performed at baseline and 4, 6, and 8 weeks post-doxorubicin initiation, whereas invivo superoxide production was measured at 4 and 6 weeks with 18F-DHMT positron emission tomography. Left ventricular ejection fraction (LVEF) was not significantly decreased until 6 weeks post-doxorubicin treatment, whereas myocardial superoxide production was significantly elevated at 4 weeks. 18F-DHMT imaging detected an elevation in cardiac superoxide production before a fall in LVEF in rodents and may allow for early cardiotoxicity detectionin cancer patients.

Early myocardial deformation abnormalities in breast cancer survivors.

To evaluate the role of 2D myocardial strain (rate) imaging in the detection of early subclinical cardiotoxicity in breast cancer survivors treated with an anthracycline-based chemotherapeutic regimen. 57 adult breast cancer survivors were analyzed 1year after therapy. All patients underwent biomarker analysis and 2D echocardiography consisting of conventional echocardiographic and strain (rate) parameters. Conventional echocardiographic values were normal. Global longitudinal strain was normal, but 18% of patients showed a >2 SD decrease when individually compared to reference values. This subgroup showed a decrease in end-systolic and end-diastolic volumes and an increase in left ventricular mass. Radial and circumferential strain rates were significantly decreased in the whole study group. 2D myocardial strain (rate) imaging showed abnormalities in breast cancer survivors, while conventional echocardiographic values remained normal, rendering 2D myocardial strain (rate) imaging an interesting tool for the early detection of anthracycline-induced cardiotoxicity.

Biomarkers for the early detection of anthracycline-induced cardiotoxicity: current status

Cardiotoxicity is a well-known and potentially serious complication of anticancer therapy. Anthracycline-based chemotherapy represents the greatest risk. Early detection of cardiotoxicity is crucial for applying preventive and supportive therapeutic strategies. Various methods have been recommended for monitoring of cardiotoxicity. In our conditions, echocardiography and electrocardiography are routinely used. However, this approach shows low sensitivity for the early prediction of cardiomyopathy when the possibilities of appropriate management could still improve the patient's outcome. Recently, biomarkers of cardiac injury have been investigated in the assessment of chemotherapy-induced cardiotoxicity. Cardiospecific biomarkers, such as cardiac troponins, show high diagnostic efficacy in the early subclinical phase of the disease before the clinical onset of cardiomyopathy. Increase in their concentrations correlates with disease severity. As for natriuretic peptides, some studies, including ours, have shown promising results. Definitive evidence of their diagnostic and prognostic role in this context is still lacking and natriuretic peptides have not been routinely used for monitoring of cardiotoxicity in clinical practice. Other perspective biomarkers of cardiotoxicity in oncology are under study, especially heart-type fatty acid-binding protein (H-FABP) and glycogen phosphorylase BB (GPBB). Our studies using GPBB have provided encouraging results. However, the available data are limited and their practical use in this context cannot be recommended until their clinical efficacy is clearly defined. This review covers the current status of biomarkers for the early detection of anthracycline-induced cardiotoxicity. The authors present in brief, their own experience with multiple biomarkers in the detection of cardiotoxicity.

Early Detection of Anthracycline-Induced Cardiotoxicity in Long-Term Survivors of Acute Lymphoblastic Leukemia Treated with Low Cumulative Dose.

We investigated the left ventricular (LV) function, using for the first time strain (S) and strain rate (SR) imaging, in long-term survivors affected by acute lymphoblastic leukemia treated with a low cumulative dose of anthracyclines, and in presence of a normal global LV systolic and diastolic function. A total of 21 were enrolled in the study. The mean cumulative dose of anthracylines was 180 mg/m2 (range: 120-210 mg/m2). As control group 21 age-sex matched healthy subjects were included. Radial S (17 ± 3% vs. 55 ± 6%, P < 0.0001) and SR (2.1 ± 0.3 vs. 3.0 ± 0.8 1\\s, P < 0.0001), assessed on the midsegment of the posterior wall from the parasternal views were significantly reduced when compared with controls. Conversely, myocardial performance index was not able to discriminate between patients and controls. In this preliminary study, the myocardial deformation indices appear to be a more sensitive noninvasive technique for detecting subclinical LV dysfunction than other echocardiographic measurements.

Early detection of anthracycline-induced cardiotoxicity using two-dimensional speckle tracking echocardiography

To examine the subclinical myocardial injury shortly after epirubicin exposure in asymptomatic patients with large B-cell non-Hodgkin lymphoma using 2-dimensional (2D) speckle tracking echocardiography. Sixty-seven patients aged 52.58 ± 13.86 years with large B-cell non-Hodgkin lymphoma treated with epirubicin were studied. Echocardiography was performed at baseline and 1 day after completion of the therapy. Global and regional longitudinal (LS), circumferential (CS) and radial strain (RS), standard deviation of time to peak LS (TLS-SD), CS (TCS-SD), RS(TRS-SD) were calculated using 2D speckle tracking echocardiography. Despite normal left ventricular ejection fraction, global LS (-18.30 ± 1.87% vs.-16.18 ± 1.92%; p < 0.01), CS (-20.37 ± 2.89% vs. -18.25 ± 2.40%, p < 0.01) and RS (39.95 ± 5.79% vs. 36.15 ± 5.79%, p < 0.01), were remarkably reduced compared to baseline values. However, TLS-SD, TCS-SD and TRS-SD showed no significant difference after epirubicin exposure. Hypertension was an independent predictor of reduction of global LS, CS and RS. Subtle abnormalities in myocardial systolic function were present in asymptomatic patients shortly after anthracycline exposure, which could be detected by 2D speckle tracking echocardiography.

Abstract 2435: The Role of Myocardial Longitudinal Strain in Monitoring Subclinical Heart Failure in Survivors of Childhood Cancer

Objectives: Previous studies have demonstrated that myocardial longitudinal strain and strain rate is decreased in asymptomatic patients treated with anthracyclines. In this study, the relation between global myocardial longitudinal strain, conventional echocardiographic parameters, NT-pro-BNP levels, cumulative anthracycline dosage and follow up duration was investigated in a large group of asymptomatic long term survivors of childhood cancer. Methods: 79 asymptomatic survivors (45% children) underwent a detailed echocardiographic examination for obtaining conventional parameters and global myocardial longitudinal strain values in 4-chamber view. In addition to this, we collected blood samples for NT-pro-BNP estimation. Results: the survivors had a mean age of 20 years (range: 6 –37 years), a mean follow up duration of 14 years (range 5–27 years) and a mean cumulative anthracycline dose of 240 mg/m 2 (range 50 –524 mg/m 2 ). Reduced global myocardial longitudinal strain was significantly related to an EF&lt;55% (p&lt;0.001) and to reduced left ventricular posterior wall thickness in diastole indexed by body surface area (LVPWd/BSA) (p&lt;0.003). Reduced myocardial global longitudinal strain was not related to abnormal NT-pro-BNP levels, follow up duration and cumulative anthracycline dosage. Conclusion: reduced global myocardial longitudinal strain is related to subclinical heart failure, e.g. abnormal EF and reduced LVPWd/BSA in asymptomatic survivors of childhood cancer. The role of myocardial strain in the early detection of anthracycline-induced cardiotoxicity needs to be explored by further longitudinal prospective studies.

Role of heart rate variability for early detection of anthracycline-induced cardiotoxicity and prediction of reduction in left ventricular ejection fraction

Role of heart rate variability for early detection of anthracycline-induced cardiotoxicity and prediction of reduction in left ventricular ejection fraction

Usefulness of myocardial performance index and biochemical markers for early detection of anthracycline-induced cardiotoxicity in adults

Anthracycline therapy is limited by cardiotoxicity. Currently no diagnostic parameter is available allowing ubiquitous and reliable detection of preclinical anthracycline cardiomyopathy and prediction of prognosis. In 100 consecutive patients receiving anthracycline-based chemotherapy serial measurements of left ventricular systolic and diastolic function, Tei index (a Doppler echocardiographic parameter of global ventricular function), cardiac troponin T (cTnT) and NT-probrain natriuretic peptides (BNP) at baseline and during 1-year follow-up were performed. Mean ejection fraction (LVEF) significantly decreased immediately after completion of anthracycline therapy (mean dose 226.1 +/- 8.3 mg/m(2)) und further declined during follow-up (65.9 +/- 0.6% Vs. 61.6 +/- 0.7%; P < 0.001), while mean E/A ratio decreased after 6 months (P = 0.05). No patient presented with cardiac symptoms. The Tei index increased after therapy in the majority of patients (78.8%) compared with pre-therapy values indicating myocardial alteration in more patients than previously recognized. cTnT levels did not exceed the upper limit of the normal range in any patient. Seven patients had low-level elevations of cTnT. Only one of these patients developed a concomitant decrease in LVEF. Mean N-terminal-pro-BNP (NT-proBNP) levels did not significantly change after anthracycline administration. However, in 13 patients (15.3%) a marked, transient increase of NT-proBNP was obtained after the first anthracycline cycle without cardiac dysfunction presumably due to altered cardiac loading conditions during chemotherapy. Low to moderate doses of anthracyclines resulted in subclinical myocardial alteration in more patients than so far noticed. Clinical implications of increased Tei index remain to be determined in long-term. Our results do not support that assessment of cTnT or BNP levels may safely replace serial echocardiographic evaluation of systolic and diastolic function for the monitoring of anthracycline cardiotoxicity.

THE ROLE OF BIOMARKERS IN THE EARLY DETECTION OF ANTHRACYCLINE-INDUCED CARDIOTOXICITY IN CHILDREN: A Review of the Literature

Anthracycline-induced cardiotoxicity can cause serious health problems for an increasing number of children surviving childhood malignancies. Early detection of cardiac failure is critically important for the prevention and management of anthracycline-induced cardiotoxicity. The aim of this research was to determine the role of biomarkers in the early detection of anthracycline-induced cardiotoxicity in children. A literature review is presented of studies regarding the use of the biomarkers B-type natriuretic peptide (BNP), N-terminal pro-BNP (NT-pro-BNP), cardiac troponin T (cTnT), and cardiac troponin I (cTnI) in relation with anthracycline-induced cardiotoxicity in children. Six of 14 studies in children showed a significant relation between elevated biomarkers BNP, NT-pro-BNP, and cTnT and cardiac dysfunction. Six studies, although small, suggest that BNP, NT-pro-BNP, and cTnT might be useful markers in the early detection of anthracycline-induced cardiotoxicity.

CTnT can be a useful marker for early detection of anthracycline cardiotoxicity

The level of serum cardiac troponin-T (cTnT) increases with myocardial damage. We sought to assess whether cTnT level could be a useful marker for the early detection of anthracycline cardiotoxicity. Forty-one patients who had been scheduled to receive anthracycline-containing combination chemotherapy were included in the study. Serum cTnT levels were measured before (baseline) and after the first cycle of chemotherapy, and again, after the last cycle of chemotherapy. In all patients, the left ventricular ejection fraction (LVEF), fractional shortening (FS), early peak flow/atrial flow velocity (E/A) ratio, and the isovolemic relaxation time (IRT) were measured echocardiographically, both before and after the completion of chemotherapy. LVEF and FS did not change in any patients. In 21 patients (49%), the E/A ratio decreased after therapy as compared to the pre-treatment values. The decrease in E/A ratio was more prominent in patients who were older than the mean age of our study group, which was 44 years. The post-treatment IRT was prolonged compared with the pretreatment IRT (94.0 +/- 2.0 versus 85.6 +/- 10.5 ms, respectively). cTnT levels after completion of therapy were elevated in 14 (34%) patients, and exceeded the upper limit of the normal range (>0.1 ng/ml) in only one patient. cTnT levels measured after completion of therapy were significantly higher, compared with those measured at baseline and after the first cycle of therapy. In the younger age group (< or =44 years old), there was a two-fold decrease in the E/A ratio in those patients whose cTnT levels increased during the therapy, when compared with those whose cTnT levels did not change (21% versus 43%, respectively). Increased serum cTnT level can be detected in the early stages of anthracycline therapy and it is associated with diastolic dysfunction of the left ventricle. Therefore, serum cTnT level could be a useful measure for early detection of anthracycline-induced cardiotoxicity.

Usefulness of the myocardial performance index for early detection of anthracycline-induced cardiotoxicity in children

Serial surveillance for cardiotoxicity in patients receiving anthracyclines has most commonly centered on the assessment of left ventricular (LV) systolic function by either shortening fraction or ejection fraction. A myocardial performance index (MPI) has been described as a noninvasive Doppler measurement of global (systolic and diastolic) ventricular function.1,2 The MPI has been shown to correlate well with other invasive and noninvasive measures of LV function in adults.3 Recent studies in pediatric and adult patients have demonstrated that this index can quantitatively assess right ventricular dysfunction as well. 4‐6 The MPI has also been shown to have significant clinical utility. Studies have demonstrated the MPI to be a powerful predictor of outcome in adult patients with dilated cardiomyopathy and primary pulmonary hypertension.7,8 This study evaluates the clinical utility of the MPI in the serial measurement of global left and right ventricular function in pediatric cancer patients who received anthracycline antibiotics. ••• The study population consisted of 26 pediatric patients who were treated with anthracycline antibiotics as part of their chemotherapeutic regimen for childhood malignancy (age range 0.5 to 18 years, mean 9.3 6 5.4). A group of normal children served as the control population; their characteristics have

Early Detection of Anthracycline-induced Cardiotoxicity by Radio-nuclide Angiocardiography

Early Detection of Anthracycline-induced Cardiotoxicity by Radio-nuclide Angiocardiography

Early detection of anthracycline-induced cardiotoxicity by radionuclide angiocardiography.

For the early detection of myocardial damage associated with anthracycline therapy, electrocardiography, echocardiography, and radionuclide angiocardiography were used to assess cardiac function in 37 patients receiving anthracyclines (ie, adriamycin and daunorubicin at a total dose of 100-2,030 mg/m2). None of the patients developed clinical congestive heart failure. There were no significant changes of electrocardiographic and echocardiographic parameters after anthracycline administration. The left ventricular ejection fraction did not change significantly on radionuclide angiocardiography. However, the 1/3 peak filling rate (PFR) corrected by the end-diastolic count (EDC) (1/3 PFR/EDC) and the 1/3 filling fraction (1/3 FF), the indices of early diastolic function, showed a significant decrease. These findings suggest that the 1/3 PFR/EDC and 1/3 FF determined by radionuclide imaging are useful for detecting silent myocardial damage induced by anthracyclines.

Early detection of anthracycline-induced cardiotoxicity by stress radionuclide cineangiography in conjunction with Fourier amplitude and phase analysis.

Thirty-three cases of anthracycline related cardiotoxicity occurred in our institution in patients with a previously negative cardiovascular history, physical examination, and normal ECG. A total of 95 RNCA studies were performed in this group (73 studies included both rest and exercise RNCA). Twenty-one patients had two or more serial studies. Seventeen had a normal, baseline prechemotherapy study and 16 had studies done following the initiation of therapy. Fourier analysis, consisting of amplitude and phase images, were created for each study. In the subset with a baseline study, the rest LVEF became abnormal first in two of 17 patients (12%), the rest or stress LVEF in ten of 17 (59%), the rest Fourier image analysis in ten of 17 (59%), and the rest or stress Fourier image analysis in 16 of 17 (94%). In the subset without a baseline study, the rest LVEF was abnormal in ten of 16 (63%), the rest or stress LVEF in 15 of 16, (94%), the rest Fourier image analysis in 16 of 16 (100%), and the rest or stress Fourier image analysis in 16 of 16 (100%). The authors conclude that: 1) the exercise RNCA is superior to the rest RNCA alone in the early detection of anthracycline related cardiotoxicity, 2) the single most sensitive indicator of cardiotoxicity is Fourier image analysis; and 3) sequential rest and stress RNCA studies with Fourier amplitude and phase analysis is the most sensitive, noninvasive method of evaluating patients who receive potentially cardiotoxic agents.