Biomarkers to diagnose ventricular dysfunction in childhood cancer survivors: a systematic review

Heart ◽  
2018 ◽  
Vol 105 (3) ◽  
pp. 210-216 ◽  
Author(s):  
Jan M Leerink ◽  
Simone J Verkleij ◽  
Elizabeth A M Feijen ◽  
Annelies M C Mavinkurve-Groothuis ◽  
Milanthy S Pourier ◽  
...  
Keyword(s):  
Cancer Survivors ◽  
Childhood Cancer ◽  
Natriuretic Peptide ◽  
Late Onset ◽  
Childhood Cancer Survivors ◽  
Diagnostic Value ◽  
Left Ventricular ◽  
Lv Dysfunction ◽  
Low Sensitivity ◽  
Fractional Shortening

ObjectiveTo systematically review the literature and assess the diagnostic value of biomarkers in detection of late-onset left ventricular (LV) dysfunction in childhood cancer survivors (CCS) treated with anthracyclines.MethodsWe systematically searched the literature for studies that evaluated the use of biomarkers for detection of LV dysfunction in CCS treated with anthracyclines more than 1 year since childhood cancer diagnosis. LV dysfunction definitions were accepted as an ejection fraction <50% or <55% and/or a fractional shortening <28%, <29% or <30%. Contingency tables were created to assess diagnostic accuracies of biomarkers for diagnosing LV dysfunction.ResultsOf 1362 original studies screened, eight heterogeneous studies evaluating four different biomarkers in mostly asymptomatic CCS were included. In four studies, an abnormal N-terminal pro-B-type natriuretic peptide (NT-proBNP, cut-off range 63–125 ng/L) had low sensitivity (maximally 22%) and a specificity of up to 97% for detection of LV dysfunction. For troponin levels, in five studies one patient had an abnormal troponin value as well as LV dysfunction, while in total 127 patients had LV dysfunction without troponin elevations above cut-off values (lowest 0.01 ng/mL). Two studies that evaluated brain natriuretic peptide and nitric oxide were underpowered to draw conclusions.ConclusionsIn individual studies, the diagnostic value of NT-proBNP for detection of LV dysfunction in CCS is limited. Troponins have no role in detecting late-onset LV dysfunction with cut-off values as low as 0.01 ng/mL. Further study on optimal NT-proBNP cut-off values for rule out or rule in of LV dysfunction is warranted.

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

2019 ◽  
Vol 29 (12) ◽  
pp. 1494-1500
Author(s):  
Jyothsna Akam-Venkata ◽  
Gilda Kadiu ◽  
James Galas ◽  
Steven E. Lipshultz ◽  
Sanjeev Aggarwal
Keyword(s):  
Cancer Survivors ◽  
Childhood Cancer ◽  
Longitudinal Strain ◽  
Circumferential Strain ◽  
Global Longitudinal Strain ◽  
Childhood Cancer Survivors ◽  
Left Ventricular ◽  
Normal Left Ventricular ◽  
Fractional Shortening ◽  
Anthracycline Chemotherapy

AbstractAim: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.Methods and Results: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.Conclusions: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.

scholarly journals Anthracycline-Induced Cardiotoxicity in Young Cancer Patients: The Role of Carnitine

2016 ◽  
Vol 68 (Suppl. 3) ◽  
pp. 10-14 ◽  
Author(s):  
Saro H. Armenian
Keyword(s):  
Cancer Survivors ◽  
Childhood Cancer ◽  
Cancer Patients ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Childhood Cancer Survivors ◽  
Chronic Health Condition ◽  
Cardiovascular Complications ◽  
Left Ventricular

While the increased rates of survival in childhood cancers have increased progressively in recent decades, many childhood cancer survivors will have at least one chronic health condition within 40 years of age. In this regard, cardiovascular complications have emerged as a leading cause of long-term morbidity and mortality in long-term survivors of childhood cancer, likely due to exposure to anthracycline chemotherapy, and outcomes in patients with anthracycline-related cardiomyopathy remain poor. Some progress has been made in understanding the mechanisms at the basis of anthracycline-related cardiomyopathy, which appear to involve generation of reactive oxygen species, leading to mitochondrial dysfunction, followed by myocyte apoptosis and maladaptive left ventricular remodeling. Even if several guidelines currently exist for monitoring cancer patients treated with cardiotoxic therapies who are at high risk for heart failure, much work remains to be done in finding reliable markers for screening for cardiac dysfunction. Studies from our group have identified alterations in L-carnitine in cancer survivors. While additional investigations are needed, preliminary studies suggest a role for carnitine in primary prevention (during treatment) and secondary prevention (to improve function after treatment).

scholarly journals Exercise Interventions and Cardiovascular Health in Childhood Cancer: A Meta-analysis

2020 ◽  
Vol 41 (03) ◽  
pp. 141-153 ◽  
Author(s):  
Javier S. Morales ◽  
Pedro L. Valenzuela ◽  
Alba M. Herrera-Olivares ◽  
Antonio Baño-Rodrigo ◽  
Adrián Castillo-García ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Meta Analysis ◽  
Childhood Cancer Survivors ◽  
Left Ventricular ◽  
Mean Difference ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Exercise Interventions

AbstractThis study analyzed the effects of physical exercise interventions on cardiovascular endpoints in childhood cancer survivors. Relevant articles were systematically searched in PubMed, CINAHL, and Web of Science databases (since inception to 11th September 2019). We performed a meta-analysis (random effects) to determine the mean difference (expressed together with 95% confidence intervals) between pre- and post-intervention values for those cardiovascular endpoints reported in more than three studies. Twenty-seven studies (of which 16 were controlled studies) comprising 697 participants were included. Only three studies reported adverse events related to exercise interventions. Exercise resulted in an increased performance on the 6-minute walk distance test (mean difference=111 m, 95% confidence interval=39–183, p=0.003) and a non-significant trend (mean difference=1.97 ml∙kg−1∙min−1, 95% confidence interval=−0.12–4.06, p=0.065) for improvement in peak oxygen uptake. Furthermore, left ventricular ejection fraction was preserved after exercise interventions (mean difference=0.29%, 95% confidence interval=−1.41–1.99, p=0.738). In summary, exercise interventions might exert a cardioprotective effect in childhood cancer survivors by improving – or attenuating the decline of – physical capacity and cardiovascular function. Further studies, particularly randomized controlled trials, are needed to confirm these benefits.

scholarly journals Cardiovascular Status of Childhood Cancer Survivors Exposed and Unexposed to Cardiotoxic Therapy

2012 ◽  
Vol 30 (10) ◽  
pp. 1050-1057 ◽  
Author(s):  
Steven E. Lipshultz ◽  
David C. Landy ◽  
Gabriela Lopez-Mitnik ◽  
Stuart R. Lipsitz ◽  
Andrea S. Hinkle ◽  
...  
Keyword(s):  
Cancer Survivors ◽  
Childhood Cancer ◽  
Systemic Inflammation ◽  
Wall Thickness ◽  
Childhood Cancer Survivors ◽  
Left Ventricular ◽  
Atherosclerotic Disease ◽  
Cardiovascular Abnormalities ◽  
Increased Risk ◽  
Lv Mass

Purpose To determine whether cardiovascular abnormalities in childhood cancer survivors are restricted to patients exposed to cardiotoxic anthracyclines and cardiac irradiation and how risk factors for atherosclerotic disease and systemic inflammation contribute to global cardiovascular status. Methods We assessed echocardiographic characteristics and atherosclerotic disease risk in 201 survivors of childhood cancer with and without exposure to cardiotoxic treatments at a median of 11 years after diagnosis (range, 3 to 32 years) and in 76 sibling controls. Results The 156 exposed survivors had below normal left ventricular (LV) mass, wall thickness, contractility, and fractional shortening and above normal LV afterload. The 45 unexposed survivors also had below normal LV mass overall, and females had below normal LV wall thickness. Exposed and unexposed survivors, compared with siblings, had higher levels of N-terminal pro-brain natriuretic peptide (81.7 and 69.0 pg/mL, respectively, v 39.4 pg/mL), higher mean fasting serum levels of non–high-density lipoprotein cholesterol (126.5 and 121.1 mg/dL, respectively, v 109.8 mg/dL), higher insulin levels (10.4 and 10.5 μU/mL, respectively, v 8.2 μU/mL), and higher levels of high-sensitivity C-reactive protein (2.7 and 3.1 mg/L, respectively, v 0.9 mg/L; P < .001 for all comparisons). Age-adjusted, predicted-to-ideal 30-year risk of myocardial infarction, stroke, or coronary death was also higher for exposed and unexposed survivors compared with siblings (2.16 and 2.12, respectively, v 1.70; P < .01 for both comparisons). Conclusion Childhood cancer survivors not receiving cardiotoxic treatments nevertheless have cardiovascular abnormalities, systemic inflammation, and an increased risk of atherosclerotic disease. Survivorship guidelines should address cardiovascular concerns, including the risk of atherosclerotic disease and systemic inflammation, in exposed and unexposed survivors.

Impaired Left Ventricular Reserve in Childhood Cancer Survivors Treated With Anthracycline Therapy

2016 ◽  
Vol 63 (6) ◽  
pp. 1086-1090 ◽  
Author(s):  
Sachie Kaneko ◽  
Edythe B. Tham ◽  
Mark J. Haykowsky ◽  
Maria Spavor ◽  
Nee S. Khoo ◽  
...  
Keyword(s):  
Cancer Survivors ◽  
Childhood Cancer ◽  
Childhood Cancer Survivors ◽  
Left Ventricular ◽  
Anthracycline Therapy

scholarly journals Impact of Persistent Left Ventricular Regional Wall Motion Abnormalities in Childhood Cancer Survivors after Anthracycline Therapy: Assessment of Global Left Ventricular Myocardial Performance By 3D Speckle-Tracking Echocardiography

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1274-1274
Author(s):  
Hirotsugu Okuma ◽  
Hiroshi Yagasaki ◽  
Katsuyoshi Shimozawa ◽  
Hideo Mugishima ◽  
Nobutaka Noto
Keyword(s):  
Cancer Survivors ◽  
Childhood Cancer ◽  
Regional Wall Motion ◽  
Childhood Cancer Survivors ◽  
Left Ventricular ◽  
Myocardial Performance ◽  
Regional Wall Motion Abnormalities ◽  
Wall Motion Abnormalities ◽  
Group 2 ◽  
Group 1

Abstract Background: Previous studies of childhood cancer survivors demonstrated the existence of transient or persistent left ventricular (LV) regional wall motion abnormalities (WMA) after treatment with anthracyclines, but the differential impact on deformation of persistent regional WMA against global LV myocardial performance is unknown. Methods: To investigate whether childhood cancer survivors after treatment with anthracyclines with persistent LV regional WMA have a poorer LV myocardial performance compared to those without WMA, 34 long-term childhood cancer survivors (mean age 14.6±4.0 years) with a median cumulative anthracycline dose 234.7mg/m2 (range 80-625mg/m2) who had been off treatment for ≥ 5 years and a preserved LV ejection fraction (EF) (>55%), and 12 healthy control subjects, were studied by using 3D speckle-tracking echocardiography (3D STE). The 34 patients were divided into two groups according to the existence of regional WMA: group 1 (with WMA, n=14), group 2 (without WMA, n=20). 3D STE was performed to assess LV global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), global area strain (GAS), LV torsion, LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LVEF, and LV systolic dyssynchrony index (SDI: % of SD of time to peak of the 16-segment/R-R interval). Results: Of the 14 patients with WMA, regional WMA was seen at mid-anterior septum in 13 patients (92.8%) and apical septum in 1 patient (7.2%). There was no statistical difference in LVEDV, LVESV, LVEF, GLS, LV torsion or SDI derived from GLS, GCS, GAS among the 3 groups. In contrast, there were significant differences in GRS (p<0.001), GAS (p<0.018), GCS (p<0.025), and SDI derived from GRS (p<0.01) among the 3 groups. Compared with group 2, group 1 had significantly reduced GRS (14.3±6.1% vs. 33.1±10.1%, p=0.003), GCS (-23.5±3.7% vs. -33.9±6.5%, p=0.026), GAS (-34.3±5.1% vs. -45.41±6.6%, p=0.034, respectively), and greater SDI derived from GRS (16.5±5.1% vs. 6.9±2.9%, p<0.01, respectively). Moreover, existence of WMA was correlated with GRS (p<0.0001), SDI derived from GRS (p<0.0001), LVEF (p=0.036), and cumulative dose (p=0.049). Multiple linear regression analysis identified GRS as a significant determinant of the existence of WMA (β=0.751, p=0.001). Conclusion: Childhood cancer survivors after anthracycline therapy with persistent regional WMA show a poorer LV myocardial performance with mechanical dyssynchrony compared to those without regional WMA, despite a preserved LVEF. Disclosures No relevant conflicts of interest to declare.

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