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Cancer Therapy-Related Cardiac Dysfunction and Heart Failure: Part 2: Prevention, Treatment, Guidelines, and Future Directions
Hamo, Carine E; Bloom, Michelle W; Cardinale, Daniela; Ky, Bonnie; Nohria, Anju; Baer, Lea; Skopicki, Hal; Lenihan, Daniel J; Gheorghiade, Mihai; Lyon, Alexander R; Butler, Javed
Success with oncologic treatment has allowed cancer patients to experience longer cancer-free survival gains. Unfortunately, this success has been tempered by unintended and often devastating cardiac complications affecting overall patient outcomes. Cardiac toxicity, specifically the association of several cancer therapy agents with the development of left ventricular dysfunction and cardiomyopathy, is an issue of growing concern. Although the pathophysiologic mechanisms behind cardiac toxicity have been characterized, there is currently no evidence-based approach for monitoring and management of these patients. In the first of a 2-part review, we discuss the epidemiologic, pathophysiologic, risk factors, and imaging aspects of cancer therapy-related cardiac dysfunction and heart failure. In this second part, we discuss the prevention and treatment aspects in these patients and conclude with highlighting the evidence gaps and future directions for research in this area.
PMCID:4743885
PMID: 26839395
ISSN: 1941-3297
CID: 5266762
Cancer Therapy-Related Cardiac Dysfunction and Heart Failure: Part 1: Definitions, Pathophysiology, Risk Factors, and Imaging
Bloom, Michelle W; Hamo, Carine E; Cardinale, Daniela; Ky, Bonnie; Nohria, Anju; Baer, Lea; Skopicki, Hal; Lenihan, Daniel J; Gheorghiade, Mihai; Lyon, Alexander R; Butler, Javed
Advances in cancer therapy have resulted in significant improvement in long-term survival for many types of cancer but have also resulted in untoward side effects associated with treatment. One such complication that has become increasingly recognized is the development of cardiomyopathy and heart failure. Whether a previously healthy person from a cardiovascular perspective develops cancer therapy-related cardiac dysfunction or a high-risk cardiovascular patient requires cancer therapy, the team of oncologists and cardiologists must be better equipped with an evidence-based approach to care for these patients across the spectrum. Although the toxicities associated with various cancer therapies are well recognized, limitations to our understanding of the appropriate course of action remain. In this first of a 2-part review, we discuss the epidemiologic, pathophysiologic, risk factors, and imaging aspects of cancer therapy-related cardiac dysfunction and heart failure. In a subsequent second part, we discuss the prevention and treatment aspects, concluding with a section on evidence gap and future directions. We focus on adult patients in all stages of cancer therapy from pretreatment surveillance, to ongoing therapy, and long-term follow-up.
PMCID:4709035
PMID: 26747861
ISSN: 1941-3297
CID: 5266752
The bumpy road to drug development for acute heart failure
Hamo, Carine E.; Butler, Javed; Gheorghiade, Mihai; Chioncel, Ovidiu
ISI:000397234200004
ISSN: 1520-765x
CID: 5267082
How to Best Identify Elderly Individuals Who May Develop Heart Failure
Hamo, Carine E.; Butler, Javed
ISI:000386342100002
ISSN: 1932-9520
CID: 5267022
Baseline distribution of participants with depression and impaired quality of life in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial
Hamo, Carine E; Heitner, John F; Pfeffer, Marc A; Kim, Hae-Young; Kenwood, Christopher T; Assmann, Susan F; Solomon, Scott D; Boineau, Robin; Fleg, Jerome L; Spertus, John A; Lewis, Eldrin F
BACKGROUND:Previous studies have demonstrated the psychosocial effect of heart failure in patients with reduced ejection fraction. However, the effects on patients with preserved ejection fraction have not yet been elucidated. This study aimed to determine the baseline characteristics of participants with heart failure with preserved ejection fraction as it relates to impaired quality of life (QOL) and depression, identify predictors of poor QOL and depression, and determine the correlation between QOL and depression. METHODS AND RESULTS/RESULTS:Among patients enrolled in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial (TOPCAT), 3400 patients completed the Kansas City Cardiomyopathy Questionnaire, 3395 patients completed European QOL 5D Visual Analog Scale, and 1431 patients in United States and Canada completed the Patient Health Questionnaire-9. The mean summary score on the Kansas City Cardiomyopathy Questionnaire was 54.8, and on European QOL 5D Visual Analog Scale, it was 60.3; 27% of patients had moderate to severe depression. Factors associated with better Kansas City Cardiomyopathy Questionnaire and European QOL 5D Visual Analog Scale via multiple logistic regression analysis were American region, older age, no history of angina pectoris or asthma, no use of hypoglycemic agent, more activity level, and lower New York Heart Association class. Factors associated with depression via multiple logistic regression analysis included younger age, female sex, comorbid angina, chronic obstructive pulmonary disease, use of a hypoglycemic agent, lower activity level, higher New York Heart Association class, and selective serotonin reuptake inhibitor use. There were significant correlations between each of the QOL scores and depression. CONCLUSIONS:Patients with heart failure with preserved ejection fraction, who were younger had higher New York Heart Association class or comorbid angina pectoris, had lower activity levels, lived in Eastern Europe or were taking hypoglycemic agents, were more likely to have impaired QOL and depression. CLINICAL TRIAL REGISTRATION/BACKGROUND:URL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302.
PMID: 25648577
ISSN: 1941-3297
CID: 4777592
Getting to the Heart of the Matter: An Overview of Cardiac Toxicity Related to Cancer Therapy
Hamo, Carine E; Bloom, Michelle Weisfelner
With the improvement in cancer survival, long-term cardiotoxicity has become an area of increased interest. Various cancer therapies, including chemotherapy and radiation therapy can lead to cardiac toxicities with both acute and chronic manifestations. Awareness and early recognition can lead to improvement in cardiac survival and patient outcomes. The focus of this review is to summarize the cancer therapy agents most often associated with cardiovascular side effects, highlighting their mechanism of action and strategies for surveillance and prevention.
PMCID:4525792
PMID: 26309419
ISSN: 1179-5468
CID: 5266742
Vamping: stereology-based automated quantification of fluorescent puncta size and density
Dumitriu, Dani; Berger, Seth I; Hamo, Carine; Hara, Yuko; Bailey, Megan; Hamo, Amarelle; Grossman, Yael S; Janssen, William G; Morrison, John H
The size of dendritic spines and postsynaptic densities (PSDs) is well known to be correlated with molecular and functional characteristics of the synapse. Thus, the development of microscopy methods that allow high throughput quantification and measurement of PSDs is a contemporary need in the field of neurobiology. While the gold standard for measurement of sub-micrometer structures remains electron microscopy (EM), this method is exceedingly laborious and therefore not always feasible. Immunohistochemistry (IHC) is a much faster technique for identifying biological structures such as PSDs, but the fluorescent images resulting from it have traditionally been harder to interpret and quantify. Here, we report on two new image analysis tools that result in accurate size and density measurements of fluorescent puncta. Anti-PSD-95 staining was used to target synapses. The new technique of vamping, using Volume Assisted Measurement of Puncta in 2 and 3 Dimensions (VAMP2D and VAMP3D) respectively, is based on stereological principles. The fully automated image analysis tool was tested on the same subjects for whom we had previously obtained EM measurements of PSD size and/or density. Based on highly consistent results between data obtained by each of these methods, vamping offers an expedient alternative to EM that can nonetheless deliver a high level of accuracy in measuring sub-cellular structures.
PMCID:3402578
PMID: 22683698
ISSN: 1872-678x
CID: 5266732
Estrogen promotes stress sensitivity in a prefrontal cortex-amygdala pathway
Shansky, Rebecca M; Hamo, Carine; Hof, Patrick R; Lou, Wendy; McEwen, Bruce S; Morrison, John H
We have recently reported in male rats that medial prefrontal cortex (mPFC) neurons that project to the basolateral nucleus of the amygdala (BLA) are resilient to stress-induced dendritic remodeling. The present study investigated whether this also occurs in female rats. This pathway was identified using the retrograde tracer Fast Blue injected into the BLA of ovariectomized female rats with estrogen replacement (OVX + E) and without (OVX + veh). Animals were exposed for 10 days either to 2-h immobilization stress or to home cage rest, after which layer III mPFC neurons that were either retrogradely labeled by Fast Blue or unlabeled were filled with Lucifer Yellow and analyzed for apical dendritic length and spine density. No dendritic remodeling occurred in unlabeled neurons from OVX + veh or OVX + E animals. In BLA-projecting neurons, however, stress had no effect on length in OVX + veh animals, but stressed OVX + E females showed greater dendritic length than controls at intermediate branches. Stress also caused an increase in spine density in all neurons in OVX + veh animals and a spine density increase in BLA-projecting neurons in OVX + E females. Estrogen also increased spine density on BLA-projecting neurons in unstressed animals. These data demonstrate both independent effects of estrogen on pyramidal cell morphology and effects that are interactive with stress, with the BLA-projecting neurons being sensitive to both kinds of effects.
PMCID:2951843
PMID: 20139149
ISSN: 1460-2199
CID: 5266722
Stress-induced dendritic remodeling in the prefrontal cortex is circuit specific
Shansky, Rebecca M; Hamo, Carine; Hof, Patrick R; McEwen, Bruce S; Morrison, John H
Chronic stress exposure has been reported to induce dendritic remodeling in several brain regions, but it is not known whether individual neural circuits show distinct patterns of remodeling. The current study tested the hypothesis that the projections from the infralimbic (IL) area of the medial prefrontal cortex (mPFC) to the basolateral nucleus of the amygdala (BLA), a pathway relevant to stress-related mental illnesses like depression and post-traumatic stress disorder, would have a unique pattern of remodeling in response to chronic stress. The retrograde tracer FastBlue was injected into male rats' BLA or entorhinal cortex (EC) 1 week prior to 10 days of immobilization stress. After cessation of stress, FastBlue-labeled and unlabeled IL pyaramidal neurons were loaded with fluorescent dye Lucifer Yellow to visualize dendritic arborization and spine density. As has been previously reported, randomly selected (non-FastBlue-labeled) neurons showed stress-induced dendritic retraction in apical dendrites, an effect also seen in EC-projecting neurons. In contrast, BLA-projecting neurons showed no remodeling with stress, suggesting that this pathway may be particularly resilient against the effects of stress. No neurons showed stress-related changes in spine density, contrasting with reports that more dorsal areas of the mPFC show stress-induced decreases in spine density. Such region- and circuit-specificity in response to stress could contribute to the development of stress-related mental illnesses.
PMCID:2742599
PMID: 19193712
ISSN: 1460-2199
CID: 5266712