Asymptomatic Childhood Cancer Survivors Research Articles

Predicting Heart Risk in Asymptomatic Childhood Cancer Survivors

Predicting Heart Risk in Asymptomatic Childhood Cancer Survivors

Childhood Cancer Survivors Have Impaired Strain-Derived Myocardial Contractile Reserve by Dobutamine Stress Echocardiography.

Abnormal left ventricular contractile reserve (LVCR) is associated with adverse cardiac outcomes in different patient cohorts and might be useful in the detection of cardiomyopathy in childhood cancer survivors (CCS) after cardiotoxic treatment. The aim of this study was to evaluate LVCR by dobutamine stress echocardiography (DSE) combined with measures of myocardial strain in CCS previously treated with anthracyclines (AC). Fifty-three CCS (age 25.34 ± 2.44 years, 35 male) and 53 healthy controls (age 24.40 ± 2.40 years, 32 male) were included. Subjects were examined with echocardiography at rest, at low-dose (5 micrograms/kg/min), and at high-dose (40 micrograms/kg/min) dobutamine infusion. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS), strain rate (GSR), and early diastolic strain rate (GEDSR) at different DSE phases were used as measures of LVCR. The mean follow-up time among CCS was 15.8 ± 5.8 years. GLS, GSR, and LVEF were lower at rest in CCS compared to controls (p ≤ 0.03). LVEF was within the normal range in CCS. ΔGLS, ΔGSR, and ΔGEDSR but not ΔLVEF were lower in CCS compared to controls after both low- (p ≤ 0.048) and high-dose dobutamine infusion (p ≤ 0.023). We conclude that strain measures during low-dose DSE detect impaired myocardial contractile reserve in young CCS treated with AC at 15-year follow-up. Thus, DSE may help identify asymptomatic CCS at risk for heart failure and allows for tailored follow-up accordingly.

Management of childhood cancer survivors at risk for thyroid function abnormalities: A Delphi study.

Thyroid function abnormalities can occur after treatment for childhood cancer. Evidence for the management of thyroid dysfunction among asymptomatic childhood cancer survivors (CCS) is lacking. We used a Delphi consensus methodology to expand guidelines for screening asymptomatic CCS at risk for thyroid dysfunction and explore recommendations for the clinical management of abnormal results. A Delphi panel of 40 expert physicians representing oncology, endocrinology, and primary care participated in three rounds of anonymous, iterative questionnaires formatted as clinical scenarios. Consensus is defined as ≥ 90% of panelists agree with recommendation and disagreement as < 70% agree. Panelists reached consensus that CCS treated with radiation including neck, total body, whole brain, brain including the hypothalamic-pituitary axis (HPA), and therapeutic meta-iodobenzylguanidine (MIBG) should have annual, lifelong screening using serum thyroid-stimulating hormone (TSH) and free T4 starting within one year off-treatment (98%). Panelists disagreed on continuing to screen CCS for thyroid dysfunction after immunotherapy associated with acute thyroid injury (31%-50%). There was also disagreement on indications for brain (17%-43%) or thyroid (50%-65%) imaging, laboratory tests to assess the HPA (29%-75%), and TSH threshold to initiate treatment of subclinical hypothyroidism. Lack of evidence was the most frequent rationale panelists offered for not recommending additional testing or medications. Panelists' recommendations did not vary by geography, specialty, or survivorship clinical experience. Consensus was reached on most recommendations for screening and management of cancer treatment-related thyroid dysfunction. Screening after completion of thyroid-toxic immunotherapy, indications for imaging, and treatment of subclinical hypothyroidism are areas of disagreement for further investigation.

Consensus Recommendations for Managing Childhood Cancer Survivors at Risk for Stroke After Cranial Irradiation: A Delphi Study.

There is insufficient evidence to support stroke prevention guidelines for childhood cancer survivors (CCS) treated with cranial irradiation for CNS tumors or other childhood cancers involving the CNS. We used a systematic consensus-building methodology to develop expert recommendations and define areas of controversy in managing asymptomatic CCS at risk for stroke. A Delphi process was used to query a multispecialty panel of 45 physicians from the United States/Canada, with expertise in CCS, about their stroke screening and management practices (imaging, referrals, laboratory testing, and medications). Three iterative rounds of anonymous, scenario-based questionnaires, building on panelists' aggregate responses, were used to reach consensus (≥90% agreement), agreement (89%-70% agree), or to understand the rationale for disagreement (<70% agree). All 45 physicians participated in the first 2 rounds and 44 in the third. Panelists reached consensus on indications for referral to neurology and laboratory screening for modifiable cerebral vascular disease (CVD) risk factors in most scenarios. Panelists agreed that aspirin therapy is not recommended in the scenario of normal neuroimaging (86% agreed). Decisions about aspirin therapy in scenarios with abnormal neuroimaging were deferred to specialists; almost all agreed with not using aspirin for cavernomas with no evidence for previous hemorrhage (93%) and using aspirin for both large vessel CVD (93%) and small vessel CVD with evidence of previous stroke (86%). Clinical decisions that remain controversial (less than 70% agreement) include neuroimaging to screen asymptomatic CCS for CVD, referral to neurology for cavernomas, aspirin use in the setting of cavernomas with previous hemorrhage, or with evidence for small vessel CVD and no previous stroke, and indications for statins. Overall, pediatric neurologists/neuro-oncologists and radiation oncologists were more likely to advocate for screening and interventions. Despite lack of evidence to guide the management of CCS at risk for stroke, expert recommendations and rationale developed by consensus methodology are helpful to support clinical decision-making.

Characterization of Cardiac, Vascular, and Metabolic Changes in Young Childhood Cancer Survivors.

Background: Childhood cancer survivors (CCS) are at an increased risk for cardiovascular diseases (CVD). It was the primary aim of this study to determine different measures of cardiac, carotid, lipid, and apolipoprotein status in young adult CCS and in healthy controls.Methods: Cardiac and common carotid artery (CCA) structure and function were measured by ultrasonography. Lipids and apolipoproteins were measured in the blood. Peripheral arterial endothelial vasomotor function was assessed by measuring digital reactive hyperemia index (PAT-RHI) using the Endo-PAT 2000.Results: Fifty-three CCS (20–30 years, 35 men) and 53 sex-matched controls were studied. The CCS cohort was divided by the median dose of anthracyclines into a low anthracycline dose (LAD) group (50–197 mg/m2, n = 26) and a high anthracycline dose (HAD) group (200–486 mg/m2, n = 27). Carotid distensibility index (DI) and endothelial function determined by PAT-RHI were both lower in the CCS groups compared with controls (p < 0.05 and p = 0.02). There was no difference in carotid intima media thickness. Atherogenic apolipoprotein-B (Apo-B) and the ratio between Apo-B and Apoliprotein-A1 (Apo-A1) were higher in the HAD group compared with controls (p < 0.01). Apo-B/Apo-A1-ratio was over reference limit in 29.6% of the HAD group, in 15.4% of LAD group, and in 7.5% of controls (p = 0.03). Measured lipid markers (low density lipoprotein and total cholesterol and triglycerides) were higher in both CCS groups compared with controls (p < 0.05). Systolic and diastolic function were measurably decreased in the HAD group, as evidenced by lower EF (p < 0.001) and lower é-wave (p < 0.005) compared with controls. CCA DI correlated with Apo-B/Apo-A1-ratio and Apo-A1. Follow-up time after treatment correlated with decreased left ventricular ejection fraction (p = 0.001).Conclusion: Young asymptomatic CCS exhibit cardiac, vascular, lipid, and apolipoprotein changes that could account for increased risk for CVD later in life. These findings emphasize the importance of cardiometabolic monitoring even in young CCS.

Left ventricular dyssynchrony in long-term childhood cancer survivors treated with anthracyclines: a retrospective cross-sectional study

The purpose of this study was to investigate left ventricular contraction patterns in asymptomatic Childhood cancer survivors (CCS) using two-dimensional speckle tracking echocardiography (2DSTE). Left ventricular longitudinal and circumferential myocardial parameters were assessed using 2DSTE, in asymptomatic CCS and age matched healthy controls. Time to peak (T2P) systolic strain was quantified. Dyssynchrony index (DI) was measured by calculating the standard deviation of T2P systolic strain of six segments in each view. Difference between T2P systolic longitudinal strain of septal and lateral wall was also assessed as a parameter for dyssynchrony. We included 115 CCS with a median age of 17.2 years (range 5.6–39.5) and a median follow up of 11.3 years (range 4.9–29.5) and 119 controls. Conventional echocardiographic parameters and global longitudinal strain were significantly decreased in CCS compared to controls (p < 0.01 and p = 0.02, respectively). Dyssynchrony index did not differ between CCS and controls. There was a clinically insignificant smaller absolute difference between T2P systolic longitudinal of septal and lateral wall in CCS compared to controls. We showed no difference in longitudinal or circumferential left ventricular dyssynchrony in CCS compared to controls using 2DSTE. Future research should focus on assessing dyssynchrony in more segments and a larger CCS population, using both 2D and 3DSTE.

Screening colonoscopy according to guidelines in long-term survivors of childhood cancer-results of a population-based study.

To report on findings in screening colonoscopies in long-term survivors of childhood cancer treated with abdominopelvic irradiation (RT). Screening colonoscopies were introduced at the Slovenian outpatient follow-up clinic in 2015, according to the Children's Oncology Group guidelines. In January 2019, 54 patients who received abdominopelvic irradiation for Hodgkin disease, Wilms tumour or dysgerminoma at the age of 0-16 between 1968 and 1995 were eligible for screening colonoscopy, and until December 2019, twenty-eight asymptomatic patients have undergone this examination. Patients were 1-16 (median 13) years old at cancer diagnosis and had colonoscopy 24-47 (median 36) years after diagnosis. They received abdominopelvic irradiation with the dose 16-46 (median 30) Gy. Adenomatous lesions were found in 18 patients (64%) and advanced adenomatous lesions in one-third. Patients who received abdominopelvic RT with a dose below 30 Gy had 75% incidence of adenomatous lesions and in those who received a dose of 30 Gy or more the incidence was 60%. Alkylating agents did not have impact on this incidence. In this first population-based study of screening colonoscopies in asymptomatic survivors of childhood cancer, we provided new evidence for 64% incidence of adenomatous lesions after abdominopelvic RT with the dose above or below 30 Gy. Screening colonoscopies are of vital importance in patients treated with abdominal RT in childhood.

COVID-19 in pediatric survivors of childhood cancer and hematopoietic cell transplantation from a single center in New York City.

Childhood cancer survivors are at increased risk for treatment‐related late effects; data are lacking on how coronavirus disease 2019 (COVID‐19) infection impacts this cohort. We assessed COVID‐19‐related symptoms, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) IgG seroprevalence, and rate of COVID‐19‐related hospitalization among 321 asymptomatic survivors of childhood cancer or transplantation seen for routine long‐term follow‐up between May and September 2020 in a New York City tertiary cancer center. While 10.9% (n = 35) reported possible COVID‐19‐related symptoms, 7.8% (n = 20) of those tested had positive SARS‐CoV‐2 IgG, and one patient (0.3%) required COVID‐19‐related hospitalization. This report suggests that childhood cancer survivors appear to be at relatively low risk for COVID‐19 complications.

Cardiovascular disease and asymptomatic childhood cancer survivors: Current clinical practice.

BackgroundIt is poorly understood how cardiovascular screening in asymptomatic childhood cancer survivors (CCS) is applied to and impacts clinical care.ObjectivesTo describe the current role of cardiovascular screening in the clinical care of asymptomatic CCS.MethodsAt 50 pediatric academic medical centers, a childhood cancer survivorship clinic director, pediatric cardiologist, and adult cardiologist with a focus on CCS were identified and invited to participate in a survey. Surveys were managed electronically. Categorical data were analyzed using nonparametric methods.ResultsOf the 95 (63%) respondents, 39% were survivorship practitioners, and 61% were cardiologists. Eighty‐eight percent of survivorship practitioners reported that greater than half of CCS received cardiovascular screening. CCS followed by adult cardiology were more likely to be seen by a cardio‐oncologist. Those followed by pediatric cardiology were more likely to be seen by a heart failure/transplant specialist. Common reasons for referral to cardiology were abnormal cardiovascular imaging or concerns a CCS was at high risk for cardiovascular disease. Ninety‐two percent of cardiologists initiated angiotensin converting enzyme inhibitor or angiotensin receptor blocker therapy for mild systolic dysfunction. Adult cardiologists initiated beta‐blocker therapy for less severe systolic dysfunction compared to pediatric cardiologists (P < .001). Pediatric cardiologists initiated mineralocorticoid therapy for less severe systolic dysfunction compared to adult cardiologists (P = .025). Practitioners (93%) support a multi‐institutional collaboration to standardize cardiovascular care for CCS.ConclusionsWhile there is much common ground in the clinical approach to CCS, heterogeneity is evident. This highlights the need for cohesive, multi‐institutional, standardized approaches to cardiovascular management in CCS.

Effect of anthracycline therapy on myocardial function and markers of fibrotic remodelling in childhood cancer survivors.

Anthracyclines are a cornerstone of paediatric cancer treatment. We aimed to quantify myocardial cardiac magnetic resonance (CMR) native T1 (NT1) and extracellular volume fraction (ECV) as markers of fibrosis in a cohort of childhood cancer survivors (CCS). A cohort of CCS in remission underwent CMR T1 mapping. Diastolic function was assessed by echocardiography. Results were compared to a cohort of normal controls of similar age and gender. Fifty-five CCS and 46 controls were included. Both groups had similar mean left ventricular (LV) NT1 values (999 ± 36 vs. 1007 ± 32 ms, P = 0.27); ECV was higher (25.6 ± 6.9 vs. 20.7 ± 2.4%, P = 0.003) and intracellular mass was lower (37.5 ± 8.4 vs. 43.3 ± 9.9g/m2, P = 0.02) in CCS. The CCS group had lower LV ejection fraction (EF) and LV mass index with otherwise normal diastolic function in all but one patient. The proportion of subjects with elevated ECV compared to controls did not differ between subgroups with normal or reduced LV EF (22% vs. 28%; P = 0.13) and no correlations were found between LVEF and ECV. While average values remained within normal range, mitral E/E' (6.6 ± 1.6 vs. 5.9 ± 0.9, P = 0.02) was higher in CCS. Neither NT1 nor ECV correlated with diastolic function indices or cumulative anthracycline dose. There is evidence for mild diffuse extracellular volume expansion in some asymptomatic CCS; myocyte loss could be part of the mechanism, accompanied by subtle changes in systolic and diastolic function. These findings suggest mild myocardial damage and remodelling after anthracycline treatment in some CCS which requires continued monitoring.

Left ventricle segmental function in childhood cancer survivors using speckle-tracking echocardiography.

Anthracycline-associated cardiotoxicity in childhood cancer survivors may relate to global or segmental left ventricular abnormalities from associated thromboembolic events and myocardial microinfarcts. We characterized left ventricular segmental changes by two-dimensional speckle-tracking echocardiography in anthracycline-treated asymptomatic childhood cancer survivors. Childhood cancer survivors' echocardiograms with normal left ventricular fractional shortening >1 year after anthracycline chemotherapy were studied. Cancer-free control children had normal echocardiograms. Apical two-, three-, and four-chamber peak systolic left ventricular longitudinal and global longitudinal strain, and peak systolic left ventricular radial and circumferential strain at papillary muscle levels were analyzed. The mean (standard deviation) age was 12.7 (3.8) years in 41 childhood cancer survivors. The median (interquartile range) follow-up after anthracycline chemotherapy was 4.73 (2.15-8) years. The median (range) cumulative anthracycline dose was 160.2 (60-396.9) mg/m2. In childhood cancer survivors, the mean (standard deviation) left ventricular longitudinal strain was lower in two- (-18.6 [3.2] versus -21.3 [2.5], p < 0.001), three- (-16.3 [6.0] versus -21.7 [3.0], p < 0.001), and four- (-17.6 [2.7] versus -20.8 [2.0], p < 0.001) chamber views compared to controls. The left ventricular global longitudinal strain (-17.6 [2.7] versus -21.3 [2.0]) and circumferential strain (-20.8 [4.3] versus -23.5 [2.6], p < 0.001) were lower in childhood cancer survivors. Among childhood cancer survivors, 12 out of 16 left ventricular segments had significantly lower longitudinal strain than controls. Asymptomatic anthracycline-treated childhood cancer survivors with normal left ventricular fractional shortening had lower global longitudinal and circumferential strain. The left ventricular longitudinal strain was lower in majority of the segments, suggesting that anthracycline cardiotoxicity is more global than regional.

Regional practice norms for the care of childhood cancer survivors at risk for cardiomyopathy: A Delphi study.

Treatment-associated cardiomyopathy is a leading cause of morbidity and mortality for childhood cancer survivors (CCS). As evidence is not available to guide the management of CCS at risk for cardiomyopathy, we aim to describe the collective opinion of regional experts for the care of these patients using a consensus-based Delphi methodology. Nineteen physicians from the New England region who care for CCS treated with cardiotoxic therapy (anthracyclines, thoracic radiation) participated in a Delphi panel querying their management approach, using three rounds of anonymous questionnaires formatted as five clinical scenarios. Consensus ≥ 89% agreement. The response rate was 100% for the first round and 95% for subsequent rounds. Panelists reached consensus on screening asymptomatic CCS with serial echocardiograms (94%) and electrocardiograms (89%), with some disagreement on frequency during pregnancy (83%). All panelists agreed with exercise promotion, with no restrictions on weight training. Consensus was reached on indications for referrals; cardiology for asymptomatic left ventricular dysfunction (ALVD) (100%) and maternal-fetal medicine for pregnancy (94%). In the scenario of ALVD, there was disagreement on the benefit of additional cardiac testing (50% cardiologists recommended cardiac MRI), and although all panelists endorsed treating with angiotension-converting enzyme (ACE) inhibitors, most adult cardiologists (75%) also recommended therapy with beta blockers, compared with none of the pediatric cardiologists or primary-care physicians. Despite a lack of evidence to guide the management of CCS at risk for cardiomyopathy, a panel of regional physicians reached consensus on managing most clinical scenarios. A controversial area requiring further study is the medical management of ALVD.

Subclinical anthracycline-induced cardiotoxicity in long-term follow-up of asymptomatic childhood cancer survivors: Assessment by speckle tracking echocardiography.

Survivors of childhood cancer treated with anthracyclines carry the risk for developing late-onset cardiotoxicity. The purpose of this study was to evaluate left ventricular (LV) function in this patient group and compare it with healthy controls by means of conventional and speckle tracking echocardiography (STE) after exposure to chemotherapy. Conventional and STE were performed in 45 childhood cancer survivors (mean age 11±4.6; 26 male) treated with anthracyclines (median cumulative dosage 240mg/m2 ; range, 100-460) and compared with age, gender and body surface area matched healthy controls. Follow-up period after chemotherapy was 21.9±17.8months. Blood samples were taken from survivors and controls to determine brain natriuretic peptide (BNP). Following anthracycline exposure, pediatric cancer survivors had lower longitudinal, radial anteroseptal, and radial anterior strain values compared to controls (P<.05). The calculated global longitudinal and global radial strain values were lower compared to the control group (P<.05). Both groups had normal ejection fraction (EF) and fractional shortening (FS). Brain natriuretic peptide (BNP) levels of both groups were in the normal range. Despite normal EF and FS, children exposed to anthracycline therapy may have late-onset subtle changes of LV strain values measured by STE. Whether these changes of strain can predict future risk of developing heart failure needs to be explored in further studies.

Is screening for abnormal ECG patterns justified in long-term follow-up of childhood cancer survivors treated with anthracyclines?

ECG and echocardiography are noninvasive screening tools to detect subclinical cardiotoxicity in childhood cancer survivors (CCSs). Our aims were as follows: (1) assess the prevalence of abnormal ECG patterns, (2) determine the agreement between abnormal ECG patterns and echocardiographic abnormalities; and (3) determine whether ECG screening for subclinical cardiotoxicity in CCSs is justified. We retrospectively studied ECG and echocardiography in asymptomatic CCSs more than 5 years after anthracycline treatment. Exclusion criteria were abnormal ECG and/or echocardiogram at the start of therapy, incomplete follow-up data, clinical heart failure, cardiac medication, and congenital heart disease. ECG abnormalities were classified using the Minnesota Code. Level of agreement between ECG and echocardiography was calculated with Cohen kappa. We included 340 survivors with a mean follow-up of 14.5 years (range 5-32). ECG was abnormal in 73 survivors (21.5%), with ventricular conduction disorders, sinus bradycardia, and high-amplitude R waves being most common. Prolonged QTc (>0.45 msec) was found in two survivors, both with a cumulative anthracycline dose of 300 mg/m2 or higher. Echocardiography showed abnormalities in 44 survivors (12.9%), mostly mild valvular abnormalities. The level of agreement between ECG and echocardiography was low (kappa 0.09). Male survivors more often had an abnormal ECG (corrected odds ratio: 3.00, 95% confidence interval: 1.68-5.37). Abnormal ECG patterns were present in 21% of asymptomatic long-term CCSs. Lack of agreement between abnormal ECG patterns and echocardiographic abnormalities may suggest that ECG is valuable in long-term follow-up of CCSs. However, it is not clear whether these abnormal ECG patterns will be clinically relevant.

Screening for cardiac dysfunction in anthracycline-exposed childhood cancer survivors.

To examine the utility and reliability of obtaining early echocardiographic measurements of left ventricular (LV) remodeling as well as blood biomarkers of cardiac injury in asymptomatic childhood cancer survivors at risk for LV dysfunction and congestive heart failure due to past exposure to anthracycline chemotherapy. Using a cross-sectional design, anthracycline-exposed childhood cancer survivors with preserved ejection fraction (EF; ≥50%) were evaluated using early echocardiographic indices and blood biomarkers of LV dysfunction. Survivors treated with ≥300 mg/m(2) anthracyclines [high risk (HR): n = 100] were compared with those treated with <300 mg/m(2) anthracyclines [low risk (LR): n = 50] and matched healthy controls (HC: n = 50). All echocardiograms were interpreted by an institutional cardiologist and a study cardiologist blinded to risk status. Time from diagnosis was comparable for HR (12.0 years) and LR (13.2 years, P = 0.8) survivors. Echocardiograms: HR had lower LV thickness-dimension ratio (Z-score: HR: -0.62, LR: -0.03, HC: -0.02; P < 0.001), increased LV wall stress (HR: 66.7 g/cm(2), LR: 56.6 g/cm(2), HC: 54.2 g/cm(2); P < 0.01), and higher myocardial performance index (HR: 0.51, LR: 0.46, HC: 0.46; P < 0.01). Interobserver correlation (clinical/blinded reading) for all echocardiographic indices was excellent (range: R = 0.76-0.97, P < 0.001). Blood biomarkers: With the exception of NT-proBNP (r = 0.28, P < 0.01), there was no correlation between blood biomarkers (B-type natriuretic peptide, Troponin-T, ST-2, Galectin-3) and LV dysfunction. Childhood cancer survivors with preserved EF 10+ years from anthracycline exposure had dose-dependent changes in echocardiographic markers of LV dysfunction.

Carnitine and Cardiac Dysfunction in Childhood Cancer Survivors Treated with Anthracyclines

Childhood cancer survivors are at high risk of developing congestive heart failure (CHF) compared with the general population, and there is a dose-dependent increase in CHF risk by anthracycline dose. The mechanism by which this occurs has not been fully elucidated. Metabolomics, the comprehensive profile of small-molecule metabolites, has the potential to provide insight into the pathogenesis of disease states and discover diagnostic markers for therapeutic targets. We performed echocardiographic testing and blood plasma metabolomic analyses (8 pathways; 354 metabolites) in 150 asymptomatic childhood cancer survivors previously treated with anthracyclines. Median time from cancer diagnosis to study participation was 12.4 years (2.6-37.9 years); 64% were treated for a hematologic malignancy; median anthracycline dose was 350 mg/m(2) (25-642 mg/m(2)). Thirty-five (23%) participants had cardiac dysfunction-defined as left ventricular end-systolic wall stress >2SD by echocardiogram. Plasma levels of 15 compounds in three metabolic pathways (carbohydrate, amino acid, and lipid metabolism) were significantly different between individuals with cardiac dysfunction and those with normal systolic function. After adjusting for multiple comparisons, individuals with cardiac dysfunction had significantly lower plasma carnitine levels [relative ratio (RR), 0.89; P < 0.01] in relation to those with normal systolic function. These findings may facilitate the development of primary prevention (treatment of carnitine deficiency before/during anthracycline administration) and secondary prevention strategies (screening and treatment in long-term survivors) in patients at highest risk for CHF. Cancer Epidemiol Biomarkers Prev; 23(6); 1109-14. ©2014 AACR.

Childhood cancer, endocrine disorders, and cohort studies

Childhood cancer, endocrine disorders, and cohort studies

Atrial Fibrillation Innovation Program: Transitioning Emergency Atrial Fibrillation Management (Team) - Lessons From A Feasibility Trial

s S99 single-shot acquisition T1 mapping sequence. Subjects also performed peak aerobic capacity (VO2) testing, a vertical jump test, and a wall squat test. RESULTS: Compared to controls, cancer survivors had significantly lower LVEF (57.5 6.2% vs. 64.3 5.5%, P<0.001), LV indexed mass (48.9 13.7 g/m vs. 62.7 10.2 g/m, P<0.001), LV mass/volume ratio (0.67 0.17 vs. 0.89 0.17, P<0.001), and peak VO2 (28.1 4.9 mL/kg/ min vs. 33.8 4.9 mL/kg/min, P<0.01). Between survivors and controls, there was no difference in myocardial ECVF (19.8 1.9% vs. 19.8 2.3%, P1⁄40.95), thigh ECVF (5.6 0.9% vs. 5.9 1.1%, P1⁄40.25), vertical jump distance (35.2 10.1 cm vs. 40.4 11.6 cm, P1⁄40.10), or wall squat duration (91 53 s vs. 111 58 s, P1⁄40.24). Myocardial ECVF and thigh ECVF were unrelated to cumulative anthracycline dose (r1⁄4-0.10, P1⁄40.54, and r1⁄4-0.11, P1⁄40.52, respectively). CONCLUSION: Asymptomatic childhood cancer survivors have significantly lower LVEF, LV mass, and LV mass/volume ratio, compared to controls, suggesting that conventional MRI is sensitive to early changes associated with anthracycline cardiotoxicity. Myocardial and thigh ECVF were similar between survivors and controls, suggesting that fibrosis is not a major component of these gross structural and functional changes. Long-term serial follow-up of a larger group of cancer survivors could provide further insight into the role of MRI in assessment of anthracyline cardiotoxicity in individual subjects. ACHRI Canadian Cardiovascular Society (CCS) Poster ATRIAL FIBRILLATION CLINICAL Thursday, October 17, 2013 030 ATRIAL FIBRILLATION INNOVATION PROGRAM: TRANSITIONING EMERGENCY ATRIAL FIBRILLATION MANAGEMENT (TEAM) LESSONS FROM A FEASIBILITY TRIAL N Meshkat, K Leblanc, S Bhatia, P Dorian, N Ivers, A Valentinis, L Ashley, AC Ha, K Benson, D Morra

Comprehensive profiling of cardiac dysfunction in asymptomatic childhood cancer survivors (CCS) treated with anthracyclines.

10020 Background: Anthracyclines are associated with left ventricular (LV) dysfunction in CCS with inevitable progression to congestive heart failure (CHF). Use of ejection fraction (EF) to identify LV dysfunction precludes intervention, because EF decline is a late event in the progression to CHF. Further, better understanding of pathogenesis at the cellular level could facilitate development of targeted interventions. Methods: Study design: Cross-sectional; Biomarkers: Echocardiographic (echo), and blood biomarkers in asymptomatic individuals exposed to anthracyclines ≥300mg/m2 (high-risk [HR]: n=100) compared with: i) CCS exposed to &lt;300 mg/m2 (low-risk [LR]: n=50): and ii) matched healthy controls (Con: n=50). Pathogenesis: Metabolomic analyses (351 plasma metabolites; 64 pathways). Results: Time from dx to study was comparable for HR (12.0y) vs. LR (13.2y, p=0.8). All CCS had EF≥50%. Echo: HR had lower LV chamber thickness-dimension (T-D) ratio (Z-score: -0.62) compared with LR (-0.03) and Con (-0.02; P&lt;0.01) as well as increased LV wall stress ([ESWS] HR: 66 g/cm2, LR: 58 g/cm2, Con: 55 g/cm2, p&lt;0.01) and higher myocardial performance index ([MPI] HR: 0.51, LR: 0.46, Con: 0.46; P&lt;0.01). Blood biomarkers: HR had higher plasma NT-pro BNP (HR: 71 pg/dL, LR: 37 pg/dL, Con: 26 pg/dL; P&lt;0.01); there were no differences in troponins, Galectin-3 or ST-2. Metabolomics:Individuals with LV dysfunction (&gt;2 SD ESWS) had reduced plasma carnitine levels (relative ratio [RR]: 0.88, p&lt;0.01) contributing to altered fatty acid β-oxidation and accumulation of cardiotoxic long-chain (docosadienoate [RR=1.26], adrenate [RR=1.29]; p&lt;0.05) and essential fatty acid intermediates (dihomo-linolenate [RR=1.27], eicosapentaenoate [RR=1.23], docosapentaenoate [RR=1.46]; p&lt;0.05). Conclusions: Comprehensive profiling of anthracycline-exposed CCS with preserved EF revealed dose-dependent echo (LV ESWS, T-D ratio, MPI) and blood (NT-ProBNP) abnormalities 10+years from dx; metabolomic studies demonstrated the role of carnitine in the pathogenesis of LV dysfunction. Taken together, these findings may facilitate early detection and targeted interventions in CCS at highest risk for CHF.

Echocardiographic surveillance for asymptomatic late‐onset anthracycline cardiomyopathy in childhood cancer survivors

The optimal frequency of echocardiographic surveillance in asymptomatic childhood cancer survivors exposed to anthracyclines has not been established. We evaluated the effectiveness of performing surveillance echocardiograms according to the Children's Oncology Group's (COG) Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers in survivors ≥1 year from concluding therapy. We reviewed all children treated at our institution with anthracycline chemotherapy from 1995 to 2003. We assessed the frequency of abnormal echocardiograms according to risk groups defined in the COG guidelines, and evaluated the risk factors for an abnormal echocardiogram using Cox proportional hazards modeling. At least one echocardiogram was completed by 469/603 (77.8%) eligible survivors. Mean diagnosis age was 7.7 (SD = 4.6) years. Mean cumulative doxorubicin-equivalent dose was 205 mg/m(2) (SD = 115). Survivors completed 1,013 echocardiograms (median = 2, range =1-10) beyond 1 year after concluding therapy. Seventy-nine (16.8%) survivors had an abnormal echocardiogram at a median of 2.9 years (range 0.01-9.8) from 1 year after concluding therapy. Anthracycline dose >300 mg/m(2) (hazard ratio [HR] 3.00; 95% CI 1.51-5.98), age 1-4 years at treatment (HR 1.89; 95% CI 1.08-3.31) and radiation to a field involving the heart (HR 1.73; 95% CI 1.08-2.76) predicted an increased risk of an abnormal echocardiogram; however, even survivors in the lower COG risk groups demonstrated abnormalities. Periodic echocardiographic surveillance in childhood cancer survivors can yield abnormalities that require further evaluation. Abnormalities may become evident as early as 1 year after the conclusion of therapy and can impact even those survivors considered to be at low risk.