Cardiac computed tomography-derived extracellular volume fraction in late anthracycline-induced cardiotoxicity.
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ABSTRACT:
SUBMITTER: Egashira K
PROVIDER: S-EPMC8144341 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Extent of myocardial fibrosis in hemodialysis patients has been associated with poor prognosis. Myocardial extracellular volume (ECV) quantification using contrast enhanced cardiac computed tomography (CT) is a novel method to determine extent of myocardial fibrosis. Cardiac CT-based myocardial ECV in hemodialysis patients with those of propensity-matched non-hemodialysis control subjects were compared. Twenty hemodialysis patients (mean age, 67.4 ± 9.6 years; 80% male) and 20 propensity-matched non-hemodialysis controls (mean age, 66.3 ± 9.1 years; 85% male) who underwent comprehensive cardiac CT consisted of calcium scoring, coronary CT angiography, stress perfusion CT and delayed enhancement CT were evaluated. Myocardial ECV was significantly greater in the hemodialysis group than in the control group (33.8 ± 4.7% versus 26.6 ± 2.9%; P < 0.0001). In the hemodialysis group, modest correlation was evident between myocardial ECV and left atrial volume index (r = 0.54; P = 0.01), while there was no correlation between myocardial ECV and other cardiac parameters including left ventricular mass index and severity of myocardial ischemia. Cardiac CT-based myocardial ECV may offer a potential imaging biomarker for myocardial fibrosis in HD patients.
| S-EPMC7506012 | biostudies-literature
Project description:AimsRecovery of left ventricular ejection fraction (LVEF) after aortic valve replacement has prognostic importance in patients with aortic stenosis (AS). The mechanism by which myocardial fibrosis impacts LVEF recovery in AS is not well characterized. We sought to evaluate the predictive value of extracellular volume fraction (ECV) quantified by cardiac CT angiography (CTA) for LVEF recovery in patients with AS after transcatheter aortic valve replacement (TAVR).Methods and resultsIn 109 pre-TAVR patients with LVEF <50% at baseline echocardiography, CTA-derived ECV was calculated as the ratio of change in CT attenuation of the myocardium and the left ventricular (LV) blood pool before and after contrast administration. Early LVEF recovery was defined as an absolute increase of ≥10% in LVEF measured by post-TAVR follow-up echocardiography within 6 months of the procedure. Early LVEF recovery was observed in 39 (36%) patients. The absolute increase in LVEF was 17.6 ± 8.8% in the LVEF recovery group and 0.9 ± 5.9% in the no LVEF recovery group (P < 0.001). ECV was significantly lower in patients with LVEF recovery compared with those without LVEF recovery (29.4 ± 6.1% vs. 33.2 ± 7.7%, respectively, P = 0.009). In multivariable analysis, mean pressure gradient across the aortic valve [odds ratio (OR): 1.07, 95% confidence interval (CI): 1.03-1.11, P: 0.001], LV end-diastolic volume (OR: 0.99, 95% CI: 0.98-0.99, P: 0.035), and ECV (OR: 0.92, 95% CI: 0.86-0.99, P: 0.018) were independent predictors of early LVEF recovery.ConclusionIncreased myocardial ECV on CTA is associated with impaired LVEF recovery post-TAVR in severe AS patients with impaired LV systolic function.
| S-EPMC7822636 | biostudies-literature
Project description:AimsDoxorubicin (DOX) is an effective anti-cancer therapeutic, but is associated with both acute and late-stage cardiotoxicity. Children are particularly sensitive to DOX-induced heart failure. Here, the impact of p53 inhibition on acute vs. late-stage DOX cardiotoxicity was examined in a juvenile model.Methods and resultsTwo-week-old MHC-CB7 mice (which express dominant-interfering p53 in cardiomyocytes) and their non-transgenic (NON-TXG) littermates received weekly DOX injections for 5 weeks (25 mg/kg cumulative dose). One week after the last DOX treatment (acute stage), MHC-CB7 mice exhibited improved cardiac function and lower levels of cardiomyocyte apoptosis when compared with the NON-TXG mice. Surprisingly, by 13 weeks following the last DOX treatment (late stage), MHC-CB7 exhibited a progressive decrease in cardiac function and higher rates of cardiomyocyte apoptosis when compared with NON-TXG mice. p53 inhibition blocked transient DOX-induced STAT3 activation in MHC-CB7 mice, which was associated with enhanced induction of the DNA repair proteins Ku70 and Ku80. Mice with cardiomyocyte-restricted deletion of STAT3 exhibited worse cardiac function, higher levels of cardiomyocyte apoptosis, and a greater induction of Ku70 and Ku80 in response to DOX treatment during the acute stage when compared with control animals.ConclusionThese data support a model wherein a p53-dependent cardioprotective pathway, mediated via STAT3 activation, mitigates DOX-induced myocardial stress during drug delivery. Furthermore, these data suggest an explanation as to how p53 inhibition can result in cardioprotection during drug treatment and, paradoxically, enhanced cardiotoxicity long after the cessation of drug treatment.
| S-EPMC4133592 | biostudies-literature
Project description:Background and objectiveEpicardial adipose tissue (EAT) volume is associated with coronary plaque burden and adverse events. We aimed to determine, whether CT-derived EAT attenuation in addition to EAT volume distinguishes patients with and without myocardial infarction.Methods and resultsIn 94 patients with confirmed or suspected coronary artery disease (aged 66.9±14.7years, 61%male) undergoing cardiac CT imaging as part of clinical workup, EAT volume was retrospectively quantified from non-contrast cardiac CT by delineation of the pericardium in axial images. Mean attenuation of all pixels from EAT volume was calculated. Patients with type-I myocardial infarction (n = 28) had higher EAT volume (132.9 ± 111.9ml vs. 109.7 ± 94.6ml, p = 0.07) and CT-attenuation (-86.8 ± 5.8HU vs. -89.0 ± 3.7HU, p = 0.03) than patients without type-I myocardial infarction, while EAT volume and attenuation were only modestly inversely correlated (r = -0.24, p = 0.02). EAT volume increased per standard deviation of age (18.2 [6.2-30.2] ml, p = 0.003), BMI (29.3 [18.4-40.2] ml, p<0.0001), and with presence of diabetes (44.5 [16.7-72.3] ml, p = 0.0002), while attenuation was higher in patients with lipid-lowering therapy (2.34 [0.08-4.61] HU, p = 0.04). In a model containing volume and attenuation, both measures of EAT were independently associated with the occurrence of type-I myocardial infarction (OR [95% CI]: 1.79 [1.10-2.94], p = 0.02 for volume, 2.04 [1.18-3.53], p = 0.01 for attenuation). Effect sizes remained stable for EAT attenuation after adjustment for risk factors (1.44 [0.77-2.68], p = 0.26 for volume; 1.93 [1.11-3.39], p = 0.02 for attenuation).ConclusionCT-derived EAT attenuation, in addition to volume, distinguishes patients with vs. without myocardial infarction and is increased in patients with lipid-lowering therapy. Our results suggest that assessment of EAT attenuation could render complementary information to EAT volume regarding coronary risk burden.
| S-EPMC5570500 | biostudies-literature
Project description:ObjectivesThe association between extracellular volume (ECV) measured by computed tomography angiography (CTA) and clinical outcomes was evaluated in low-flow low-gradient (LFLG) aortic stenosis (AS) patients undergoing transcatheter aortic valve replacement (TAVR).BackgroundPatients with LFLG AS comprise a high-risk group with respect to clinical outcomes. Although ECV, a marker of myocardial fibrosis, is traditionally measured with cardiac magnetic resonance, it can also be measured using cardiac CTA. The authors hypothesized that in LFLG AS, increased ECV may be associated with adverse clinical outcomes.MethodsIn 150 LFLG patients with AS who underwent TAVR, ECV was quantified using pre-TAVR CTA. Echocardiographic and clinical information including all-cause death and heart failure rehospitalization (HFH) was obtained from electronic medical records. A Cox proportional hazards model was used to evaluate the association between ECV and death+HFH.ResultsDuring a median follow-up of 13.9 months (range 0.07 to 28.9 months), there were 31 death+HFH events (21%). Patients who experienced death+HFH had a greater median Society of Thoracic Surgery score (9.9 vs. 4.7; p < 0.01), lower left ventricular ejection fraction (42.3 ± 20.2% vs. 52.7 ± 17.2%; p < 0.01), lower mean transvalvular gradient (24.9 ± 8.9 mm Hg vs. 28.1 ± 7.3 mm Hg; p = 0.04) and increased mean ECV (35.5 ± 9.6% vs. 29.9 ± 8.2%; p < 0.01) compared with patients who did not experience death+HFH. In a multivariable Cox proportional hazards model, increase in ECV was associated with increase in death+HFH, (hazard ratio per 1% increase: 1.04, 95% confidence interval: 1.01 to 1.09; p < 0.01).ConclusionsIn patients with LFLG AS, CTA measured increase in ECV is associated with increased risk of adverse clinical outcomes post-TAVR and may thus serve as a useful noninvasive marker for prognostication.
| S-EPMC7850162 | biostudies-literature
Project description:AimsDoxorubicin (DOX) is a widely used and effective anti-cancer therapeutic. DOX treatment is associated with both acute and late onset cardiotoxicity, limiting its overall efficacy. Here, the impact of cardiomyocyte cell cycle activation was examined in a juvenile model featuring aspects of acute and late onset DOX cardiotoxicity.Methods and resultsTwo-week old MHC-cycD2 transgenic mice (which express cyclin D2 in postnatal cardiomyocytes and exhibit sustained cardiomyocyte cell cycle activity; D2 mice) and their wild type (WT) littermates received weekly DOX injections for 5 weeks (25 mg/kg cumulative dose). One week after the last DOX treatment (acute stage), cardiac function was suppressed in both groups. Acute DOX cardiotoxicity in D2 and WT mice was associated with similar increases in the levels of cardiomyocyte apoptosis and Ku70/Ku80 expression (markers of DNA damage and oxidative stress), as well as similar reductions in hypertrophic cardiomyocyte growth. Cardiac dysfunction persisted in WT mice for 13 weeks following the last DOX treatment (late stage) and was accompanied by increased levels of cardiomyocyte apoptosis, Ku expression, and myocardial fibrosis. In contrast, D2 mice exhibited a progressive recovery in cardiac function, which was indistinguishable from saline-treated animals by 9 weeks following the last DOX treatment. Improved cardiac function was accompanied by reductions in the levels of late stage cardiomyocyte apoptosis, Ku expression, and myocardial fibrosis.ConclusionThese data suggest that cardiomyocyte cell cycle activity can promote recovery of cardiac function and preserve cardiac structure following DOX treatment.
| S-EPMC6452322 | biostudies-literature
Project description:Background Myocardial extracellular volume fraction (ECV), measured by cardiac magnetic resonance imaging, is a useful prognostic marker for patients who have undergone aortic valve replacement (AVR) for aortic stenosis. However, the prognostic significance of ECV measurements based on computed tomography (CT) is unclear. This study evaluated the association between ECV measured with dual-energy CT and clinical outcomes in patients with aortic stenosis who underwent transcatheter or surgical AVR. Methods and Results We retrospectively enrolled 95 consecutive patients (age, 84.0±5.0 years; 75% women) with severe aortic stenosis who underwent preprocedural CT for transcatheter AVR planning. ECV was measured using iodine density images obtained by delayed enhancement dual-energy CT. The primary end point was a composite outcome of all-cause death and hospitalization for heart failure after AVR. The mean ECV measured with CT was 28.1±3.8%. During a median follow-up of 2.6 years, 22 composite outcomes were observed, including 15 all-cause deaths and 11 hospitalizations for heart failure. In Kaplan-Meier analysis, the high ECV group (≥27.8% [median value]) had significantly higher rates of composite outcomes than the low ECV group (<27.8%) (log-rank test, P=0.012). ECV was the only independent predictor of adverse outcomes on multivariable Cox regression analysis (hazards ratio, 1.25; 95% CI, 1.10‒1.41; P<0.001). Conclusions Myocardial ECV measured with dual-energy CT in patients who underwent aortic valve intervention was an independent predictor of adverse outcomes after AVR.
| S-EPMC8649554 | biostudies-literature
Project description:ImportanceAnthracyclines are part of many effective pediatric cancer treatment protocols. Most pediatric oncology treatment groups assume that the hematologic toxicity of anthracycline agents is equivalent to their cardiotoxicity; for example, Children's Oncology Group substitution rules consider daunorubicin and epirubicin isoequivalent to doxorubicin, whereas mitoxantrone and idarubicin are considered 4 to 5 times as toxic as doxorubicin.ObjectiveTo determine optimal dose equivalence ratios for late-onset cardiomyopathy between doxorubicin and other anthracyclines or the anthraquinone mitoxantrone.Design, setting, and participantsThis multicenter cohort study of childhood cancer survivors who survived 5 or more years analyzed data pooled from 20 367 participants in the Childhood Cancer Survivor Study treated from 1970 to 1999, 5741 participants in the Dutch Childhood Oncology Group LATER study diagnosed between 1963 and 2001, and 2315 participants in the St Jude Lifetime study treated from 1962 to 2005.ExposuresCumulative doses of each agent (the anthracyclines doxorubicin, daunorubicin, epirubicin, and idarubicin; and the anthraquinone mitoxantrone) along with chest radiotherapy exposure were abstracted from medical records.Main outcomes and measuresCardiomyopathy (severe, life-threatening, or fatal) by 40 years of age. Agent-specific Cox proportional hazards models evaluated cardiomyopathy risk, adjusting for chest radiotherapy, age at cancer diagnosis, sex, and exposure to anthracyclines or to an anthraquinone. An agent-specific cardiomyopathy equivalence ratio (relative to doxorubicin) was estimated for each dose category as a ratio of the hazard ratios, and then a weighted mean determined the overall agent-specific equivalence ratio across all dose categories.ResultsOf 28 423 survivors (46.4% female; median age at cancer diagnosis 6.1 years [range, 0.0-22.7 years]), 9330 patients received doxorubicin, 4433 received daunorubicin, 342 received epirubicin, 241 received idarubicin, and 265 received mitoxantrone. After a median follow-up of 20.0 years (range, 5.0-40.0 years) following receipt of a cancer diagnosis, 399 cardiomyopathy cases were observed. Relative to doxorubicin, the equivalence ratios were 0.6 (95% CI, 0.4-1.0) for daunorubicin, 0.8 (95% CI, 0.5-2.8) for epirubicin, and 10.5 (95% CI, 6.2-19.1) for mitoxantrone. Outcomes were too rare to generate idarubicin-specific estimates. Ratios based on a continuous linear dose-response relationship were similar for daunorubicin (0.5 [95% CI, 0.4-0.7]) and epirubicin (0.8 [95% CI, 0.3-1.4]). The relationship between mitoxantrone and doxorubicin appeared better characterized by a linear exponential model.Conclusions and relevanceIn a large data set assembled to examine long-term cardiomyopathy risk in childhood cancer survivors, daunorubicin was associated with decreased cardiomyopathy risk vs doxorubicin, whereas epirubicin was approximately isoequivalent. By contrast, the current hematologic-based doxorubicin dose equivalency of mitoxantrone (4:1) appeared to significantly underestimate the association of mitoxantrone with long-term cardiomyopathy risk.
| S-EPMC6490232 | biostudies-literature
Project description:Background:Cancer treatment with anthracyclines may lead to an increased incidence of cardiac disease due to cardiotoxicity, as they may cause irreversible myocardial fibrosis. So far, the proposed methods for screening patients for cardiotoxicity have led to only limited success, while the analysis of myocardial extracellular volume (mECV) at cardiac magnetic resonance (CMR) has shown promising results, albeit requiring a dedicated exam. Recent studies have found strong correlations between mECV values obtained through computed tomography (CT), and those derived from CMR. Thus, our purpose was to evaluate the feasibility of estimating mECV on thoracic contrast-enhanced CT performed for staging or follow-up in breast cancer patients treated with anthracyclines, and, if feasible, to assess if a rise in mECV is associated with chemotherapy, and persistent over time. Methods:After ethics committee approval, female patients with breast cancer who had undergone at least 2 staging or follow-up CT examinations at our institution, one before and one shortly after the end of chemotherapy including anthracyclines were retrospectively evaluated. Patients without available haematocrit, with artefacts in CT images, or who had undergone radiation therapy of the left breast were excluded. Follow-up CT examinations at longer time intervals were also analysed, when available. mECV was calculated on scans obtained at 1, and 7 min after contrast injection. Results:Thirty-two female patients (aged 57±13 years) with pre-treatment haematocrit 38%±4%, and ejection fraction 64%±6% were analysed. Pre-treatment mECV was 27.0%±2.9% at 1 min, and 26.4%±3.8% at 7 min, similar to values reported for normal subjects in the literature. Post-treatment mECV (median interval: 89 days after treatment) was 31.1%±4.9%, and 30.0%±5.1%, respectively, values significantly higher than pre-treatment values at all times (P<0.005). mECV at follow-up (median interval: 135 days after post-treatment CT) was 31.0%±4.5%, and 27.7%±3.7%, respectively, without significant differences (P>0.548) when compared to post-treatment values. Conclusions:mECV values from contrast-enhanced CT scans could play a role in the assessment of myocardial condition in breast cancer patients undergoing anthracycline-based chemotherapy. CT-derived ECV could be an imaging biomarker for the monitoring of therapy-related cardiotoxicity, allowing for potential secondary prevention of cardiac damage, using data derived from an examination that could be already part of patients' clinical workflow.
| S-EPMC7242290 | biostudies-literature
Project description:Delayed-enhanced dual-energy computed tomography (DECT) can evaluate the extent and degree of myocardial fibrosis while coronary CT angiography (CCTA) is a widely accepted coronary artery evaluation method. We sought to describe the role of combined cardiac CT for the evaluation of underlying etiology in patients with newly diagnosed heart failure with reduced ejection fraction (HFrEF). Sixty-three consecutive patients (31 men, 63 ± 16 years) with newly diagnosed HFrEF were enrolled in this prospective study. Coronary artery disease and myocardial fibrosis were evaluated on CCTA and DECT, respectively, and the tentative underlying etiologies of heart failure (HF) were determined with combinations of findings from both CTs. Concordance between tentative etiologies from cardiac CT and final etiologies from clinical decisions within a 2-year follow-up was assessed. Eighteen patients were diagnosed with ischemic HF on initial cardiac CT, and the final diagnosis was not changed. Another 45 patients with nonischemic HF included tentative etiologies of dilated cardiomyopathy (n = 32, 71.1%), sarcoidosis or myocarditis (n = 8, 17.8%), amyloidosis (n = 2, 4.4%), noncompaction (n = 2, 4.4%) and arrhythmogenic right ventricular cardiomyopathy (n = 1, 2.2%). Five nonischemic HF patients showed different etiologies between initial cardiac CT and clinical decisions. The concordance between cardiac CT and clinical decisions was 92.1%. A high degree of concordance was achieved between tentative etiologies from cardiac CT and final diagnoses from clinical decisions. Combined cardiac CT is a feasible, safe and effective imaging tool for the initial evaluation of newly diagnosed HFrEF patients.
| S-EPMC7408702 | biostudies-literature