Anthracycline-Associated T1 Mapping Characteristics Are Elevated Independent of the Presence of Cardiovascular Comorbidities in Cancer Survivors.
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ABSTRACT: Cardiovascular magnetic resonance T1 mapping characteristics are elevated in adult cancer survivors; however, it remains unknown whether these elevations are related to age or presence of coincident cardiovascular comorbidities.We performed blinded cardiovascular magnetic resonance analyses of left ventricular T1 and extracellular volume (ECV) fraction in 327 individuals (65% women, aged 64±12 years). Thirty-seven individuals had breast cancer or a hematologic malignancy but had not yet initiated their treatment, and 54 cancer survivors who received either anthracycline-based (n=37) or nonanthracycline-based (n=17) chemotherapy 2.8±1.3 years earlier were compared with 236 cancer-free participants. Multivariable analyses were performed to determine the association between T1/ECV measures and variables associated with myocardial fibrosis. Age-adjusted native T1 was elevated pre- (1058±7 ms) and post- (1040±7 ms) receipt of anthracycline chemotherapy versus comparators (965±3 ms; P<0.0001 for both). Age-adjusted ECV, a marker of myocardial fibrosis, was elevated in anthracycline-treated cancer participants (30.4±0.7%) compared with either pretreatment cancer (27.8±0.7%; P<0.01) or cancer-free comparators (26.9±0.2%; P<0.0001). T1 and ECV of nonanthracycline survivors were no different than pretreatment survivors (P=0.17 and P=0.16, respectively). Native T1 and ECV remained elevated in cancer survivors after accounting for demographics (including age), myocardial fibrosis risk factors, and left ventricular ejection fraction or myocardial mass index (P<0.0001 for all).Three years after anthracycline-based chemotherapy, elevations in myocardial T1 and ECV occur independent of underlying cancer or cardiovascular comorbidities, suggesting that imaging biomarkers of interstitial fibrosis in cancer survivors are related to prior receipt of a potentially cardiotoxic cancer treatment regimen.
<h4>Background</h4>Cardiovascular magnetic resonance T1 mapping characteristics are elevated in adult cancer survivors; however, it remains unknown whether these elevations are related to age or presence of coincident cardiovascular comorbidities.<h4>Methods and results</h4>We performed blinded cardiovascular magnetic resonance analyses of left ventricular T1 and extracellular volume (ECV) fraction in 327 individuals (65% women, aged 64±12 years). Thirty-seven individuals had breast cancer or a ...[more]
Project description:While developments in cancer therapeutics have greatly reduced morbidity and mortality in females with breast cancer, it comes at a cost of an increased risk of cardiovascular complications. In particular, anthracyclines, like doxorubicin, which are a mainstay of current chemotherapy regimens, are associated with dose-dependent cardiotoxicity. Exercise has been widely accepted as an effective intervention in reducing cardiovascular risk in a variety of different clinical conditions. However, the benefits of exercise in anthracycline-mediated cardiotoxicity are not clearly understood. First, this review discusses the pre-clinical studies which have elucidated the cardioprotective mechanisms of aerobic and resistance exercise in improving cardiovascular function in the setting of anthracycline treatment. Next, it aims to summarize the results of aerobic and resistance exercise clinical trials conducted in females with breast cancer who received anthracycline-based chemotherapy. The review further discusses the current exercise guidelines for women undergoing chemotherapy and contraindications for exercise. Finally, the review addresses gaps in research, specifically the need for further clinical trials to establish a recommended exercise prescription within this patient population.
Project description:BackgroundChemotherapy-induced cardiotoxicity is a well-recognized adverse effect of chemotherapy. Quantitative T1-mapping cardiovascular magnetic resonance (CMR) is useful for detecting subclinical myocardial changes in anthracycline-induced cardiotoxicity. The aim of the present study was to histopathologically validate the T1 and T2 mapping parameters for the evaluation of diffuse myocardial changes in rat models of cardiotoxicity.MethodsRat models of cardiotoxicity were generated by injecting rats with doxorubicin (1 mg/kg, twice a week). CMR was performed with a 9.4 T ultrahigh-field scanner using cine, pre-T1, post-T1 and T2 mapping sequences to evaluate the left ventricular ejection fraction (LVEF), native T1, T2, and extracellular volume fraction (ECV). Histopathological examinations were performed and the association of histopathological changes with CMR parameters was assessed.ResultsFive control rats and 36 doxorubicin-treated rats were included and classified into treatment periods. In the doxorubicin-treated rats, the LVEF significantly decreased after 12 weeks of treatment (control vs. 12-week treated: 73 ± 4% vs. 59 ± 9%, P = 0.01). Increased native T1 and ECV were observed after 6 weeks of treatment (control vs. 6-week treated: 1148 ± 58 ms, 14.3 ± 1% vs. 1320 ± 56 ms, 20.3 ± 3%; P = 0.005, < 0.05, respectively). T2 values also increased by six weeks of treatment (control vs. 6-week treated: 16.3 ± 2 ms vs. 10.3 ± 1 ms, P < 0.05). The main histopathological features were myocardial injury, interstitial fibrosis, inflammation, and edema. The mean vacuolar change (%), fibrosis (%), and inflammation score were significantly higher in 6-week treated rats than in the controls (P = 0.03, 0.03, 0.02, respectively). In the univariable analysis, vacuolar change showed the highest correlation with native T1 value (R = 0.60, P < 0.001), and fibrosis showed the highest correlation with ECV value (R = 0.78, P < 0.001). In the multiple linear regression analysis model, vacuolar change was a significant factor for change in native T1 (P = 0.01), and vacuolar change and fibrosis were significant factors for change in ECV (P = 0.006, P < 0.001, respectively) by adding other histopathological parameters (i.e., inflammation and edema scores) CONCLUSIONS: Quantitative T1 and T2 mapping CMR is a useful non-invasive tool reflecting subclinical histopathological changes in anthracycline-induced cardiotoxicity.
Project description:BACKGROUND:Myocardial recovery after primary percutaneous coronary intervention in acute myocardial infarction is variable and the extent and severity of injury are difficult to predict. We sought to investigate the role of cardiovascular magnetic resonance T1 mapping in the determination of myocardial injury very early after treatment of ST-segment elevation myocardial infarction (STEMI). METHODS:STEMI patients underwent 3?T cardiovascular magnetic resonance (CMR), within 3?h of primary percutaneous intervention (PPCI). T1 mapping determined the extent (area-at-risk as %left ventricle, AAR) and severity (average T1 values of AAR) of acute myocardial injury, and related these to late gadolinium enhancement (LGE), and microvascular obstruction (MVO). The characteristics of myocardial injury within 3?h was compared with changes at 24-h to predict final infarct size. RESULTS:Forty patients were included in this study. Patients with average T1 values of AAR ?1400?ms within 3?h of PPCI had larger LGE at 24-h (33% ±14 vs. 18% ±10, P?=?0.003) and at 6-months (27% ±9 vs. 12% ±9; P?<?0.001), higher incidence and larger extent of MVO (85% vs. 40%, P?=?0.016) & [4.0 (0.5-9.5)% vs. 0 (0-3.0)%, P?=?0.025]. The average T1 value was an independent predictor of acute LGE (? 0.61, 95%CI 0.13 to 1.09; P?=?0.015), extent of MVO (? 0.22, 95%CI 0.03 to 0.41, P?=?0.028) and final infarct size (? 0.63, 95%CI 0.21 to 1.05; P?=?0.005). Receiver-operating-characteristic analysis showed that T1 value of AAR obtained within 3-h, but not at 24-h, predicted large infarct size (LGE >?9.5%) with 100% positive predictive value at the optimal cut-off of 1400?ms (area-under-the-curve, AUC 0.88, P?=?0.006). CONCLUSION:Hyper-acute T1 values of the AAR (within 3?h post PPCI, but not 24?h) predict a larger extent of MVO and infarct size at both 24?h and 6?months follow-up. Delayed CMR scanning for 24?h could not substitute the significant value of hyper-acute average T1 in determining infarct characteristics.
Project description:Recent large-scale studies have observed differences in survival following treatment for early laryngeal carcinoma depending on treatment type but were not able to take sociodemographic, comorbidity, and facility data into account. The objective of this study was to determine whether survival differences across treatment types persist when these factors are included in the analysis.Retrospective cohort analysis.Linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data files.Medicare beneficiaries who were identified through the SEER registries (1991-2009) as having T1 glottic squamous cell carcinoma (scca) and a known treatment type were included.A total of 2338 patients with incident T1 glottic scca were identified. Most were white and male. Treatment type was radiation only in 47%, local surgery and radiation in 39%, and local surgery only in 14%. Black race and increased comorbidities were associated with worse survival. When sociodemographics, comorbidities, and facility characteristics were taken into account, survival differences were observed across treatment types, with those receiving local surgery demonstrating better overall and cancer-specific survival.These results suggest that following treatment of T1 glottic scca, there may be survival differences across treatment types beyond those explained by sociodemographic, comorbidity, and facility characteristics.
Project description:BackgroundAlthough breast cancer survivors are at risk for cardiovascular disease (CVD) from treatment late effects, evidence to inform long-term and age-specific cardiovascular surveillance recommendations is lacking.MethodsWe conducted a retrospective cohort study of 10 211 women diagnosed with first primary unilateral breast cancer in Kaiser Permanente Washington or Colorado (aged 20 years and older, survived ≥1 year). We estimated multivariable adjusted hazard ratios (HRs) for associations between initial chemotherapy regimen type (anthracycline and/or trastuzumab, other chemotherapies, no chemotherapy [referent]) and CVD risk, adjusted for patient characteristics, other treatments, and CVD risk factors. Cumulative incidence was calculated considering competing events.ResultsAfter 5.79 median years, 14.67% of women developed CVD (cardiomyopathy and/or heart failure [HF], ischemic heart disease, stroke). Women treated with anthracyclines and/or trastuzumab had a higher risk of CVD compared with no chemotherapy (adjusted HR = 1.53, 95% confidence interval [CI] = 1.31 to 1.79), persisting at least 5 years postdiagnosis (adjusted HR5-<10 years = 1.85, 95% CI = 1.44 to 2.39; adjusted HR≥10 years = 1.83, 95% CI = 1.34 to 2.49). Cardiomyopathy and/or HF risks were elevated among women treated with anthracyclines and/or trastuzumab compared with no chemotherapy, especially for those aged younger than 65 years (adjusted HR20-54years = 2.97, 95% CI = 1.72 to 5.12; adjusted HR55-64years = 2.21, 95% CI = 1.52 to 3.21), differing for older women (adjusted HR≥65 years = 1.32, 95% CI = 0.97 to 1.78), and at least 5 years postdiagnosis (adjusted HR5-<10years = 1.89, 95% CI = 1.35 to 2.64; adjusted HR≥10 years = 2.21, 95% CI = 1.52 to 3.20). Anthracyclines and/or trastuzumab receipt was associated with increased ischemic heart disease risks after 5 or more years (adjusted HR5-<10years = 1.51, 95% CI = 1.06 to 2.14; adjusted HR≥10 years = 1.86, 95% CI = 1.18 to 2.93) with no clear age effects, and stroke risk (adjusted HR = 1.33, 95% CI = 1.05 to 1.69), which did not vary by time or age. There was some evidence of long-term cardiomyopathy and/or HF and ischemic heart disease risks with other chemotherapies. Among women aged younger than 65 treated with anthracyclines and/or trastuzumab, up to 16% developed CVD by 10 years (20-54 years = 6.91%; 55-64 years = 16.00%), driven by cardiomyopathy and/or HF (20-54 years = 3.90%; 55-64 years = 9.78%).ConclusionsWe found increased long-term risks of cardiomyopathy and/or HF and ischemic heart disease among breast cancer survivors treated with anthracyclines and/or trastuzumab and increased cardiomyopathy and/or HF risk among women aged younger than 65 years.
Project description:A reliable, non-invasive diagnostic method is needed for early detection and serial monitoring of cardiotoxicity, a well-known side effect of chemotherapy. This study aimed to assess the feasibility of T1-mapping cardiac magnetic resonance imaging (CMR) for evaluating subclinical myocardial changes in a doxorubicin-induced cardiotoxicity rabbit model. Adult male New Zealand White rabbits were injected twice-weekly with doxorubicin and subjected to CMR on a clinical 3T MR system before and every 2-4 weeks post-drug administration. Native T1 and extracellular volume (ECV) values were measured at six mid-left ventricle (LV) and specific LV lesions. Histological assessments evaluated myocardial injury and fibrosis. Three pre-model and 11 post-model animals were included. Myocardial injury was observed from 3 weeks. Mean LV myocardium ECV values increased significantly from week 3 before LV ejection fraction decreases (week 6), and ECVs of the RV upper/lower insertion sites and papillary muscle exceeded those of the LV. The mean native T1 value in the mid-LV increased significantly increased from week 6, and LV myocardium ECV correlated strongly with the degree of fibrosis (r = 0.979, p < 0.001). Myocardial T1 mapping, particularly ECV values, reliably and non-invasively detected early cardiotoxicity, allowing serial monitoring of chemotherapy-induced cardiotoxicity.
Project description:PURPOSE:To evaluate the accuracy and repeatability of a free-breathing, non-electrocardiogram (ECG), continuous myocardial T1 and extracellular volume (ECV) mapping technique adapted from the Multitasking framework. METHODS:The Multitasking framework is adapted to quantify both myocardial native T1 and ECV with a free-breathing, non-ECG, continuous acquisition T1 mapping method. We acquire interleaved high-spatial resolution image data and high-temporal resolution auxiliary data following inversion-recovery pulses at set intervals and perform low-rank tensor imaging to reconstruct images at 344 inversion times, 20 cardiac phases, and 6 respiratory phases. The accuracy and repeatability of Multitasking T1 mapping in generating native T1 and ECV maps are compared with conventional techniques in a phantom, a simulation, 12 healthy subjects, and 10 acute myocardial infarction patients. RESULTS:In phantoms, Multitasking T1 mapping correlated strongly with the gold-standard spin-echo inversion recovery (R2 = 0.99). A simulation study demonstrated that Multitasking T1 mapping has similar myocardial sharpness to the fully sampled ground truth. In vivo native T1 and ECV values from Multitasking T1 mapping agree well with conventional MOLLI values and show good repeatability for native T1 and ECV mapping for 60 seconds, 30 seconds, or 15 seconds of data. Multitasking native T1 and ECV in myocardial infarction patients correlate positively with values from MOLLI. CONCLUSION:Multitasking T1 mapping can quantify native T1 and ECV in the myocardium with free-breathing, non-ECG, continuous scans with good image quality and good repeatability in vivo in healthy subjects, and correlation with MOLLI T1 and ECV in acute myocardial infarction patients.
Project description:BACKGROUND:T1 mapping based on cardiovascular magnetic resonance (CMR) is a novel approach using the magnetic relaxation T1 time as a quantitative marker for myocardial tissue composition. Various T1 mapping sequences are being used, with different strengths and weaknesses. Data comparing different sequences head to head however are sparse. METHODS:We compared three T1 mapping sequences, ShMOLLI, MOLLI and SASHA in phantoms and in a mid-ventricular slice of 40 healthy individuals (mean age 59?±?7 years, 45 % male) with low (68 %) or moderate cardiovascular risk. We calculated global and segmental T1 in vivo through exponential curve fitting and subsequent parametric mapping. We also analyzed image quality and inter-observer reproducibility. RESULTS:There was no association of T1 with cardiovascular risk groups. T1 however differed significantly depending on the sequence, with SASHA providing consistently higher mean values than ShMOLLI and MOLLI (1487?±?36 ms vs. 1174?±?37 ms and 1199?±?28 ms, respectively; p?<?0.001). This difference between sequences was much smaller in phantom measurements. In patients, segmental values were lower in the anterior wall for all sequences. Image quality, in general good for the steady-state-free-precession readouts in all sequences, was lower for SASHA parametric maps. On multivariate regression analysis, a longer T1 measured by MOLLI was correlated with lower ejection fraction and female gender. Inter-observer variability as assessed by intra-class correlation coefficients was excellent for all sequences (ShMOLLI: 0.995; MOLLI: 0.991; SASHA: 0.961; all p?<?0.001). CONCLUSION:In a cross-sectional population with low to moderate cardiovascular risk, we observed a variation in T1 mapping results between inversion-recovery vs. saturation-recovery sequences in vivo, which were less evident in phantom images, despite a small interobserver variability. Thus, physiological factors, most likely related to B1 inhomogeneities, and tissue-specific properties, like magnetization transfer, that impact T1 values in vivo, render phantom validation insufficient, and have to be further investigated for a better understanding of the clinical utility of different T1 mapping approaches. TRIAL REGISTRATION:"Canadian Alliance For Healthy Hearts and Minds" - ClinicalTrials.gov NCT02220582 ; registered August 18, 2014.
Project description:This study demonstrates a three-dimensional (3D) free-breathing native myocardial T1 mapping sequence at 3 T.The proposed sequence acquires three differently T1-weighted volumes. The first two volumes receive a saturation pre-pulse with different recovery time. The third volume is acquired without magnetization preparation and after a significant recovery time. Respiratory navigator gating and volume-interleaved acquisition are adopted to mitigate misregistration. The proposed sequence was validated through simulation, phantom experiments and in vivo experiments in 12 healthy adult subjects.In phantoms, good agreement on T1 measurement was achieved between the proposed sequence and the reference inversion recovery spin echo sequence (R2?=?0.99). Homogeneous 3D T1 maps were obtained from healthy adult subjects, with a T1 value of 1476?±?53 ms and a coefficient of variation (CV) of 6.1?±?1.4% over the whole left-ventricular myocardium. The averaged septal T1 was 1512?±?60 ms with a CV of 2.1?±?0.5%.Free-breathing 3D native T1 mapping at 3 T is feasible and may be applicable in myocardial assessment. The proposed 3D T1 mapping sequence is suitable for applications in which larger coverage is desired beyond that available with single-shot parametric mapping, or breath-holding is unfeasible.
Project description:In this study RNA-Seq was performed in anthracycline- exposed childhood cancer survivors who had cardiomyopathy (cases) matched to those without cardiomyopathy (controls) to understand the pathogenesis of anthrcaycline-related cardiomyopathy
