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Left Ventricular Mass Change After Anthracycline Chemotherapy.

ABSTRACT: BACKGROUND:Myocardial atrophy and left ventricular (LV) mass reductions are associated with fatigue and exercise intolerance. The relationships between the receipt of anthracycline-based chemotherapy (Anth-bC) and changes in LV mass and heart failure (HF) symptomatology are unknown, as is their relationship to LV ejection fraction (LVEF), a widely used measurement performed in surveillance strategies designed to avert symptomatic HF associated with cancer treatment. METHODS AND RESULTS:We performed blinded, serial assessments of body weight, LVEF and mass, LV-arterial coupling, aortic stiffness, and Minnesota Living with Heart Failure Questionnaire measures before and 6 months after initiating Anth-bC (n=61) and non-Anth-bC (n=15), and in 24 cancer-free controls using paired t and χ2 tests and multivariable linear models. Participants averaged 51±12 years, and 70% were women. Cancer diagnoses included breast cancer (53%), hematologic malignancy (42%), and soft tissue sarcoma (5%). We observed a 5% decline in both LVEF (P<0.0001) and LV mass (P=0.03) in the setting of increased aortic stiffness and disrupted ventricular-arterial coupling in those receiving Anth-bC but not other groups (P=0.11-0.92). A worsening of the Minnesota Living with Heart Failure Questionnaire score in Anth-bC recipients was associated with myocardial mass declines (r=-0.27; P<0.01) but not with LVEF declines (r=0.11; P=0.45). Moreover, this finding was independent of LVEF changes and body weight. CONCLUSIONS:Early after Anth-bC, LV mass reductions associate with worsening HF symptomatology independent of LVEF. These data suggest an alternative mechanism whereby anthracyclines may contribute to HF symptomatology and raise the possibility that surveillance strategies during Anth-bC should also assess LV mass.

SUBMITTER: Jordan JH

PROVIDER: S-EPMC6729136 | biostudies-other | 2018 Jul

REPOSITORIES: biostudies-other

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Left Ventricular Mass Change After Anthracycline Chemotherapy.

Jordan Jennifer H JH Castellino Sharon M SM Meléndez Giselle C GC Klepin Heidi D HD Ellis Leslie R LR Lamar Zanetta Z Vasu Sujethra S Kitzman Dalane W DW Ntim William O WO Brubaker Peter H PH Reichek Nathaniel N D'Agostino Ralph B RB Hundley W Gregory WG

Circulation. Heart failure 20180701 7

<h4>Background</h4>Myocardial atrophy and left ventricular (LV) mass reductions are associated with fatigue and exercise intolerance. The relationships between the receipt of anthracycline-based chemotherapy (Anth-bC) and changes in LV mass and heart failure (HF) symptomatology are unknown, as is their relationship to LV ejection fraction (LVEF), a widely used measurement performed in surveillance strategies designed to avert symptomatic HF associated with cancer treatment.<h4>Methods and result ...[more]

PMID: 29991488

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Project description:OBJECTIVES:The objective of this study was to evaluate the changes in three-dimensional (3D) speckle-tracking echocardiography-derived measures of mechanics and their associations with systolic and diastolic dysfunction after anthracyclines. BACKGROUND:An improved understanding of the changes in 3D cardiac mechanics with anthracyclines may provide important mechanistic insight and identify new metrics to detect cardiac dysfunction. METHODS:A total of 142 women with breast cancer receiving doxorubicin (240 mg/m2) with or without trastuzumab underwent 3D speckle-tracking echocardiography at standardized intervals prior to, during, and annually after chemotherapy. Left ventricular ejection fraction (LVEF), global circumferential strain (GCS), global longitudinal strain (GLS), principal strain, twist, and torsion were quantified. Linear regression analyses defined the associations between clinical factors and 3D parameters. Linear regression models with cluster robust variance estimators determined the associations between 3D measures and 2-dimensional (2D) LVEF and Doppler-derived E/e' over time. RESULTS:There were significant abnormalities in 3D LVEF, GCS, GLS, and principal strain post-doxorubicin compared with control subjects (p < 0.001). The 3D parameters worsened post-anthracyclines, and only partially recovered to baseline over a median of 2.1 years (interquartile range: 1 to 4 years). Higher blood pressure and body mass index were associated with worse post-anthracycline 3D GCS and GLS, respectively. All 3D measures were associated with 2D LVEF at the same visit; only 3D LVEF, GCS, GLS, and principal strain were associated with 2D LVEF at subsequent visits (p < 0.05). In exploratory analyses, 3D LVEF and GCS were associated with subsequent systolic function independent of their corresponding 2D measures. The 3D LVEF, GCS, principal strain, and twist were significantly associated with concurrent, but not subsequent, E/e'. CONCLUSIONS:Anthracyclines result in early and persistent abnormalities in 3D mechanics. The 3D LVEF and strain measures are associated with concurrent and subsequent systolic dysfunction, and concurrent diastolic dysfunction. Future research is needed to define the mechanisms and clinical relevance of abnormal 3D mechanics.

Project description:Background: Elevated blood pressure (BP) is associated with target organ damage, such as left ventricular hypertrophy (LVH), in childhood. However, it is unclear if children who resolve elevated BP have reduced levels of left ventricular mass index (LVMI). This study aimed to examine the association between change in BP status over 2 years and LVMI among Chinese children. Methods: Data were from 1,183 children aged 6-11 years at baseline in 2017 who were followed up in 2019 in the Huantai Childhood Cardiovascular Health Cohort Study. Change in BP status over 2 years from baseline to follow-up was categorized as: persistent normal BP, resolved elevated BP (elevated BP at baseline, normal BP at follow-up), incident elevated BP (normal BP at baseline, elevated BP at follow-up), and persistent elevated BP. Elevated BP status was defined according to national reference standards as systolic or diastolic BP levels ≥ sex-, age-, and height-specific 95th percentiles. Results: LVMI levels were lowest in children with persistent normal BP (30.13 g/m2.7), higher in those with incident elevated BP (31.27 g/m2.7), and highest in those with persistent elevated BP (33.26 g/m2.7). However, LVMI levels in those who had resolved elevated BP (30.67 g/m2.7) were similar to those with persistent normal BP. In the fully adjusted model, compared with children with persistent normal BP, those with persistent elevated BP and incident elevated BP had higher LVMI at follow-up (ß = 3.131, p < 0.001; ß = 1.143, p = 0.041, respectively). In contrast, those who had resolved elevated BP did not have a significantly higher LVMI (ß = 0.545, p = 0.194) than those with persistent normal BP. Conclusion: Developing or maintaining elevated BP over a 2-year period in childhood associated with higher levels of LVMI, but those able to resolve their elevated BP status over the same period had LVMI levels that were similar with those who had normal BP at both time points. Thus, it is important to identify children with elevated BP at early time and to take effective measures to lower their BP levels, thereby reducing high LVMI levels and related cardiovascular diseases in the future.

Project description:Importance:The incidence of chemotherapy-induced cardiomyopathy is increasing and is associated with poor clinical outcomes. Objective:To assess the association of cardiac resynchronization therapy (CRT) with improvement in cardiac function, as well as clinical improvement in patients with chemotherapy-induced cardiomyopathy. Design, Setting, and Participants:The Multicenter Automatic Defibrillator Implantation Trial-Chemotherapy-Induced Cardiomyopathy was an uncontrolled, prospective, cohort study conducted between November 21, 2014, and June 21, 2018, at 12 tertiary centers with cardio-oncology programs in the United States. Thirty patients were implanted with CRT owing to reduced left ventricular ejection fraction (LVEF≤35%), New York Heart Association class II-IV heart failure symptoms, and wide QRS complex, with established chemotherapy-induced cardiomyopathy and were followed up for 6 months after CRT implantation. The date of final follow-up was February 6, 2019. Exposures:CRT implantation according to standard of care. Main Outcomes and Measures:The primary end point was change in LVEF from baseline to 6 months after initiating CRT. Secondary outcomes included all-cause mortality and change in left ventricular end-systolic volume and end-diastolic volume. Results:Among 30 patients who were enrolled (mean [SD] age, 64 [11] years; 26 women [87%]; 73% had a history of breast cancer; 20% had a history of lymphoma or leukemia), primary end point data were available for 26 patients and secondary end point data were available for 23 patients. Patients had nonischemic cardiomyopathy with left bundle branch block, median LVEF of 29%, and a mean QRS duration of 152 ms. Patients with CRT experienced a statistically significant improvement in mean LVEF at 6 months from 28% to 39% (difference, 10.6% [95% CI, 8.0%-13.3%]; P < .001). This was accompanied by a reduction in LV end-systolic volume from 122.7 to 89.0 mL (difference, 37.0 mL [95% CI, 28.2-45.8]) and reduction in LV end-diastolic volume from 171.0 to 143.2 mL (difference, 31.9 mL [95% CI, 22.1-41.6]) (both P < .001). Adverse events included a procedure-related pneumothorax (1 patient), a device pocket infection (1 patient), and heart failure requiring hospitalization during follow-up (1 patient). Conclusions and Relevance:In this preliminary study of patients with chemotherapy-induced cardiomyopathy, CRT was associated with improvement in LVEF after 6 months. The findings are limited by the small sample size, short follow-up, and absence of a control group. Trial Registration:ClinicalTrials.gov Identifier: NCT02164721.

Project description:BackgroundAnthracycline-containing chemotherapy (Anth-C) is associated with long-term cardiovascular mortality. Although cardiovascular risk assessment has traditionally focused on the heart, evidence has demonstrated that vascular dysfunction also occurs during and up to 1 year following Anth-C. Whether vascular dysfunction persists long-term or negatively influences cardiac function remains unknown. Hence, the present study evaluated ventricular-arterial coupling, in concert with measures of vascular structure and function, in the years following Anth-C.MethodsArterial elastance (Ea), end-systolic elastance (Ees), and ventricular-arterial coupling (Ea/Ees) were measured during rest and exercise using echocardiography. Resting vascular function (flow-mediated dilation) and structure (carotid intima-media thickness, arterial stiffness) were also measured.ResultsThirty breast cancer survivors (6.5 ± 3.6 years after Anth-C) with normal left ventricular ejection fraction (LVEF) (60% ± 6%) and 30 matched controls were studied. At rest, no differences were found in Ea, Ees, Ea/Ees, or LVEF between groups. The normal exercise-induced increase in Ees was attenuated in survivors at 50% and 75% of maximal workload (p < .01). Ea/Ees was also higher at all workloads in the survivors compared with the controls (p < .01). No differences in vascular structure and function were observed between the two groups (p > .05).ConclusionIn the years after Anth-C, ventricular-arterial coupling was significantly attenuated during exercise, primarily owing to decreased LV contractility (indicated by a reduced Ees). This subclinical dysfunction appears to be isolated to the heart, as no differences in Ea were observed. The previously reported adverse effects of Anth-C on the vasculature appear to not persist in the years after treatment, as vascular structure and function were comparable to controls.Implications for practiceAnthracycline-induced cardiotoxicity results in significantly impaired ventricular-arterial coupling in the years following chemotherapy, owing specifically to decreased left ventricular contractility. This subclinical dysfunction was identified only under exercise stress. A comprehensive evaluation of vascular structure and function yielded no differences between those treated with anthracyclines and controls. Combined with a stress stimulus, ventricular-arterial coupling might hold significant value beyond characterization of integrative cardiovascular function, in particular as a part of a risk-stratification strategy after anthracycline-containing chemotherapy. Although vascular function and structure were not different in this cohort, this does not undermine the importance of identifying vascular (dys)function in this population, because increases in net arterial load during exercise might amplify the effect of reductions in contractility on cardiovascular function after anthracycline-containing chemotherapy.

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Left Ventricular Mass Change After Anthracycline Chemotherapy.

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Left Ventricular Mass Change After Anthracycline Chemotherapy.

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