scholarly journals Cancer Therapy-Induced Cardiotoxicity—A Metabolic Perspective on Pathogenesis, Diagnosis and Therapy

2021 ◽  
Vol 23 (1) ◽  
pp. 441
Author(s):  
Anurag Choksey ◽  
Kerstin N. Timm

Long-term cardiovascular complications of cancer therapy are becoming ever more prevalent due to increased numbers of cancer survivors. Cancer therapy-induced cardiotoxicity (CTIC) is an incompletely understood consequence of various chemotherapies, targeted anti-cancer agents and radiation therapy. It is typically detected clinically by a reduction in cardiac left ventricular ejection fraction, assessed by echocardiography. However, once cardiac functional decline is apparent, this indicates irreversible cardiac damage, highlighting a need for the development of diagnostics which can detect CTIC prior to the onset of functional decline. There is increasing evidence to suggest that pathological alterations to cardiac metabolism play a crucial role in the development of CTIC. This review discusses the metabolic alterations and mechanisms which occur in the development of CTIC, with a focus on doxorubicin, trastuzumab, imatinib, ponatinib, sunitinib and radiotherapy. Potential methods to diagnose and predict CTIC prior to functional cardiac decline in the clinic are evaluated, with a view to both biomarker and imaging-based approaches. Finally, the therapeutic potential of therapies which manipulate cardiac metabolism in the context of adjuvant cardioprotection against CTIC is examined. Together, an integrated view of the role of metabolism in pathogenesis, diagnosis and treatment is presented.

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Raquel Araujo-Gutierrez ◽  
Kalyan R. Chitturi ◽  
Jiaqiong Xu ◽  
Yuanchen Wang ◽  
Elizabeth Kinder ◽  
...  

Abstract Background Cancer therapy-related cardiac dysfunction (CTRD) is a major source of morbidity and mortality in long-term cancer survivors. Decreased GLS predicts decreased left ventricular ejection fraction (LVEF) in patients receiving anthracyclines, but knowledge regarding the clinical utility of baseline GLS in patients at low-risk of (CTRD) is limited. Objectives The purpose of this study was to investigate whether baseline echocardiographic assessment of global longitudinal strain (GLS) before treatment with anthracyclines is predictive of (CTRD) in a broad cohort of patients with normal baseline LVEF. Methods Study participants comprised 188 patients at a single institution who underwent baseline 2-dimensional (2D) speckle-tracking echocardiography before treatment with anthracyclines and at least one follow-up echocardiogram 3 months after chemotherapy initiation. Patients with a baseline LVEF <55% were excluded from the analysis. The primary endpoint, (CTRD), was defined as an absolute decline in LVEF > 10% from baseline and an overall reduced LVEF <50%. Potential and known risk factors were evaluated using univariable and multivariable Cox proportional hazards regression analysis. Results Twenty-three patients (12.23%) developed (CTRD). Among patients with (CTRD), the mean GLS was -17.51% ± 2.77%. The optimal cutoff point for (CTRD) was -18.05%. The sensitivity was 0.70 and specificity was 0.70. The area under ROC curve was 0.70. After adjustment for cardiovascular and cancer therapy related risk factors, GLS or decreased baseline GLS ≥-18% was predictive of (CTRD) (adjusted hazards ratio 1.17, 95% confidence interval 1.00, 1.36; p = 0.044 for GLS, or hazards ratio 3.54; 95% confidence interval 1.34, 9.35; p = 0.011 for decreased GLS), along with history of tobacco use, pre-chemotherapy systolic blood pressure, and cumulative anthracycline dose. Conclusions Baseline GLS or decreased baseline GLS was predictive of (CTRD) before anthracycline treatment in a cohort of cancer patients with a normal baseline LVEF. This data supports the implementation of strain-protocol echocardiography in cardio-oncology practice for identifying and monitoring patients who are at elevated risk of (CTRD).


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Rachel Ruckdeschel Smith ◽  
Isotta Chimenti ◽  
Eduardo Marbán

Cardiosphere-derived cells (CDCs), a naturally heterogeneous mixture of cell sub-populations, were grown from percutaneous endomyocardial adult human biopsy specimens (n=6). c-Kit + and CD90 + CDCs were selected using magnetic-activated cell sorting with excellent purity as determined by flow cytometry. Immunostaining revealed that ~30% of c-Kit + CDCs expressed Nkx2.5, ~100% of CD90 + CDCs expressed procollagen type I, and ~100% of both sub-populations expressed CD105. When placed in co-culture with neonatal myocytes and fibroblasts, c-Kit + CDCs expressed cardiac troponin I, while CD90 + CDCs expressed vimentin. In order to assess the therapeutic potential of purified CDCs, acute myocardial infarcts (MIs) were created in immunodeficient mice and c-Kit + (n=16), CD90 + (n=14), or CD105 + (n=3) CDCs were injected into the border zone. Echocardiograms were performed 3 weeks post-MI to measure left ventricular ejection fraction (LVEF). CD105-injected mice were comparable to an historical control group of mixed CDC-injected mice (LVEF = 41.3±2.9% CD105 vs. 42.8±10.4% CDC [n=11], p=0.60), indicating that the sorting process did not itself impair the therapeutic potential of CDCs. c-Kit- and CD90-injected mice were indistinguishable from one another (LVEF=31.7±8.2% c-Kit vs. 32.1±11.8% CD90, p=0.92), and both groups were significantly outperformed by the CD105-injected mice (p=0.01 and p=0.03, respectively). All groups were then compared to two other historical control groups, mice treated with normal human dermal fibroblasts (NHDFs [n=7]) and mice treated with phosphate-buffered saline (PBS [n=11]). c-Kit-injected mice did significantly outperform both NHDF- (p=0.04) and PBS-injected mice (p=0.03), while more variability in the CD90-injected group resulted in nearly significant comparisons with the NHDF (p=0.08) and PBS groups (p=0.08). While the therapeutic mechanisms of action of these two distinct sub-populations are undoubtedly different, both offer similar global functional benefits in the setting of acute MI. We conclude that the spontaneously-emerging unselected CDC population serves as a therapeutic cell cocktail, and that no functional advantage is conferred by the extra step of sorting for c-Kit + or CD90 + sub-populations.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Steen ◽  
M Montenbruck ◽  
P Wuelfing ◽  
S Esch ◽  
A K Schwarz ◽  
...  

Abstract Background The incidence of cardiotoxicity during cancer therapy is underestimated due to limitations of current diagnostic tests. Current biomarkers (BNP, NT-pro-BNP, hs-Troponin, etc.) and imaging calculations (e.g. echocardiography) such as left ventricular ejection fraction (LVEF) are currently included in the guidelines to designate cardiotoxicity during cancer therapy. Unfortunately, these diagnostics identify systemic damage in symptomatic patients after the heart is unable to compensate for regional dysfunction. Fast-SENC segmental intramyocardial strain (fSENC) is a unique cardiac magnetic resonance imaging (CMR) test that regionally detects subclinical intramyocardial dysfunction in 1 heartbeat. Methods This single center, prospective Prefect Study was used to evaluate cardiotoxicity and the impact of cardioprotective therapy in Breast Cancer and Lymphoma patients (NCT03543228). fSENC was acquired with a 1.5T MRI and processed with the software to quantify intramyocardial strain. Segmental strain was measured in three short axis scans (basal, midventricular, apical) with 16 LV/6 RV longitudinal segments & three long axis scans (2-, 3-, 4-chamber) with 21 LV/5 RV circumferential segments. fSENC CMR was performed before chemotherapy, during and after anthracycline/taxane therapy, at 1 year follow-up, and as needed in between designated follow-up periods. Cardioprotective therapy was offered to patients meeting the definition of cardiotoxicity by the ESC Guidelines on Cardiotoxicity and/or ESMO Clinical Practice Guidelines or those observing a substantial decline in cardiac function. Results Two hundred eight (208) CMRs were performed in fifty-two (52) patients (44 female). Patients had an average (± stdev) age of 53 (15) yrs, BMI of 26 (5) kg/m2; 77% had breast cancer, 23% had Lymphoma. fSENC CMRs required 11 (2) min total exam time. The % of normal fSENC (segmental stain <−17%) with a threshold of 65% showed a sensitivity of 87% and specificity of 89% in detecting cardiotoxicity while echocardiography GLS with a threshold of −17% observed a sensitivity of 20% and specificity of 88%. Figure 1 shows receiver operating characteristic curves for fSENC based on the percent of normal myocardium, and echocardiography global longitudinal strain (GLS) respectively. Global fSENC had substantially lower sensitivity than segmental fSENC despite having higher accuracy than the other global metrics. Figure 1 Conclusion Segmental fSENC intramyocardial strain detects subclinical dysfunction due to cardiotoxic response of chemotherapy before other biomarkers and imaging modalities. The ability to detect the subclinical cardiotoxicity of chemotherapy agents, or other pharmacological agents that cause or worsen heart failure, enables proactive prescription of cardioprotective medications to avoid tissue remodeling that precedes systemic cardiac dysfunction and worsening of global measures such as LVEF and current biomarkers.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14018-e14018
Author(s):  
Anza Zahid ◽  
Prema P. Peethambaram ◽  
Carrie A. Thompson ◽  
Minetta C. Liu ◽  
Kathryn Jean Ruddy ◽  
...  

e14018 Background: Cancer survival rates are improving. Therefore, management of cardiovascular complications has now become a crucial clinical concern. Cardio-oncology is the sub-specialty that assists in the overall management of cancer patients in a multi-disciplinary manner. Mayo Clinic cardio-oncology practice was initiated to work closely with our oncology colleagues for early detection of cardiovascular complications in response to cancer-therapy. Majority of the patients visit our cardio-oncology clinic once, we thought it is important to study the group of patients that visited frequently due to cardiovascular complications. Aim: To evaluate the most common cardiovascular complication in patients with 2 or more visits to our cardio-oncology clinic. Methods: From 2012-2017, there were > 2500 patients visits to our clinic, with 24 patients having 2 or more visits. Data including patients’ demographics, ethnicity, chemotherapeutic medications, primary cancer type, cardiovascular risk factors, echocardiography and clinical outcomes were collected. Cardiotoxicity was defined as the decrease in left ventricular ejection fraction (LVEF) of > 10% to a value of < 53%. Heart failure was diagnosed based on Framingham’s criteria or by a cardiologist. Results: There were 19 women (80%) and 5 men (20%). Median age at the time of diagnosis was 56 years [19-76]. The most common malignancy was breast cancer (70%), followed by B-cell lymphoma (12%) and acute myeloid leukemia (8%). Thirty percent had > 2 risk factors for cardiovascular disease. 75% of the patients had an LVEF of < 53, of these 67% developed heart failure with 58% preserved and 42% reduced ejection fraction. Those with heart failure had received a mean anthracycline dose of 305 ± 91.8mg/m2. With initiation of ACEI, B-Blockers, and diuretics (GDMT) 79% showed recovery of LVEF to ≥53 during the follow up. Conclusions: In our experience, most patients who were seen at least twice in the cardio-oncology clinic for heart failure had received a dose of > 300mg/m2 anthracycline. With GDMT over 75% of the patients recovered. Care in the cardio-oncology clinic plays a key role in optimizing these clinical outcomes.


2021 ◽  
Author(s):  
Paula Postigo-Martin ◽  
Rafael Peñafiel-Burkhardt ◽  
Tania Gallart-Aragón ◽  
Miriam Alcaide-Lucena ◽  
Francisco Artacho-Cordón ◽  
...  

Abstract Objective Therapeutic exercise is already used to ameliorate some of the side effects of cancer treatment. Recent studies examined its preventive potential regarding treatment-related toxicity, which can increase the risk of functional decline and lead to disease recurrence and death. This trial will examine whether the ATOPE (Tailored Therapeutic Exercise and Recovery Strategies) program, performed before treatment (ATOPE-B), can mitigate the onset and extent of cardiotoxicity beyond that achieved when the program is followed during treatment (ATOPE-I) in recently diagnosed breast cancer patients. Methods The intervention has a preparatory phase plus 12 to 18 sessions of tailored, high-intensity exercise, and post-exercise recovery strategies. 120 women recently diagnosed with breast cancer, in risk of cardiotoxicity due to anticancer treatment awaiting surgery followed by chemotherapy and/or radiotherapy, will be randomised to either group. In a feasibility study, measurements related to recruitment rate, satisfaction with the program, adherence to them, the retention of subjects, safety, and adverse effects will be explored. In the main trial, the efficacy of these interventions will be examined. The major outcome will be cardiotoxicity, assessed echocardiographically via the left ventricular ejection fraction. Other clinical, physical, anthropometric outcomes, biological and hormonal variables, will be also assessed after diagnosis, after treatment, 1 year after treatment ends, and 3 years after treatment ends. Conclusion Given its potential effect on patient survival, the mitigation of cardiotoxicity is a priority, and physiotherapists have an important role in this mitigation. If the ATOPE-B intervention returns better cardioprotection results, it may be recommendable that patients recently diagnosed follow this program.


2021 ◽  
Author(s):  
Raquel Araujo-Gutierrez ◽  
Kalyan R. Chitturi ◽  
Jiaqiong Xu ◽  
Yuanchen Wang ◽  
Elizabeth Kinder ◽  
...  

Abstract Background: Cancer therapy-related cardiac dysfunction (CTRD) is a major source of morbidity and mortality in long-term cancer survivors. Decreased GLS predicts decreased left ventricular ejection fraction (LVEF) in patients receiving anthracyclines, but knowledge regarding the clinical utility of baseline GLS in patients at low-risk of (CTRD) is limited.Objectives: The purpose of this study was to investigate whether baseline echocardiographic assessment of global longitudinal strain (GLS) before treatment with anthracyclines is predictive of (CTRD) in a broad cohort of patients with normal baseline LVEF.Methods: Study participants comprised 188 patients at a single institution who underwent baseline 2-dimensional (2D) speckle-tracking echocardiography before treatment with anthracyclines and at least one follow-up echocardiogram 3 months after chemotherapy initiation. Patients with a baseline LVEF <55% were excluded from the analysis. The primary endpoint, (CTRD), was defined as an absolute decline in LVEF >10% from baseline and an overall reduced LVEF <50%. Potential and known risk factors were evaluated using univariable and multivariable Cox proportional hazards regression analysis.Results: Twenty-three patients (12.23%) developed (CTRD). Among patients with (CTRD), the mean GLS was -17.51% ± 2.77%. The optimal cutoff point for (CTRD) was -18.05%. The sensitivity was 0.70 and specificity was 0.70. The area under ROC curve was 0.70. After adjustment for cardiovascular and cancer therapy related risk factors, GLS or decreased baseline GLS ≥-18% was predictive of (CTRD) (adjusted hazards ratio 1.17, 95% confidence interval 1.00, 1.36; p=0.044 for GLS, or hazards ratio 3.54; 95% confidence interval 1.34, 9.35; p = 0.011 for decreased GLS), along with history of tobacco use, pre-chemotherapy systolic blood pressure, and cumulative anthracycline dose.Conclusions: Baseline GLS or decreased baseline GLS was predictive of (CTRD) before anthracycline treatment in a cohort of cancer patients with a normal baseline LVEF. This data supports the implementation of strain-protocol echocardiography in cardio-oncology practice for identifying and monitoring patients who are at elevated risk of (CTRD)


2021 ◽  
Vol 8 ◽  
Author(s):  
Sergey Kozhukhov ◽  
Nataliia Dovganych

Aim: The collaboration of cardiologists, general practitioners (GPs), and oncologists is crucial in cancer patient management. We carried out a national-based survey—The Ukrainian National Survey (UkrNatSurv)—on behalf of the Cardio-Oncology (CO) Working Group (WG) of the Ukrainian Society of Cardiology to analyze the level of knowledge in cardio-oncology.Methods: A short questionnaire was presented to specialists involved in the management of cancer patients across the country. The questionnaire was made up of eight questions concerning referred cancer patient number, CV complications of cancer therapy, diagnostic methods to detect cardiotoxicity, and drugs used for its treatment.Results: A total of 426 questionnaires of medical specialists from different regions of Ukraine were collected and analyzed; the majority of respondents were cardiologists (190), followed by GPs (177), 40 oncologists (mainly chemotherapists and hematologists), other −19 (imaging specialists, neurologists, endocrinologists, etc.). All responders were equally involved in the management of cancer patients. However, less than half of the patients have been seen before the start of cancer therapy. GPs observe the majority of patients after the end of treatment. All doctors are sufficiently aware of cancer therapy-associated CV complications. However, the necessary diagnostic tools, mostly biomarkers, are not used widely by different specialists. The criteria for cardiotoxicity, in particular, the level of reduction of the left ventricular ejection fraction (LVEF) as a marker of LV dysfunction, are not clearly understood. The specific knowledge in the management of CV complications in cancer is required.Conclusion: UkrNatSurv is the first survey in Ukraine to investigate the awareness of CO care provided to cancer patients with CV diseases (CVD) or developed CV complications. Providing such surveys among doctors involved in CO is an excellent tool to investigate the knowledge gaps in clinical practice. Therefore, the primary task is to develop a national educational CO program.


2020 ◽  
Vol 7 (1) ◽  
pp. 13-16
Author(s):  
T. Ajit Kumar ◽  
Dr. Vineeta Pande ◽  
Dr. Sharad Agarkhedkar ◽  
Dr. Mayank Surana

Background: Obesity is a disease which results from genetic or lifestyle factors. Such diseases are called Non communicable diseases. The epidemic of obesity among youth is spreading at an alarming rate due to lack of physical activity, dietary habits. The percentage of youths who are at risk of becoming overweight continues to increase. National data indicates that 16% of children aged six to nineteen years are overweight.(1)   Considering the high prevalence of  obesity among children and adolescents and its associated cardiovascular complications like hypertension, left ventricular hypertrophy, increased left ventricular mass, decreased left ventricular ejection fraction, the present study was planned to assess cardiac functions and lipid profile in obese children and adolescents. Early detection and intervention can help in reducing the complications associated with obesity. Objective: Primary objective is to assess cardiac functions and lipid profile in obese children and adolescents. Methodology: 100 obese children and adolescents in the age group 6-18 years were taken after excluding obese children with evidence of endocrine disease, malformation syndromes and iatrogenic obesity (drug treatments). Results: In the present study 7% subjects were hypertensive while 8% were prehypertensive. 71.43% children with hypertension were performing physical activity for < 30 min in 1-3 days/week while 49.11% normotensive children were performing physical activity for > 30 min per day. 3% obese children were having abnormal LVEF on 2DECHO .All the 3 obese children with abnormal LVEF were having physical activity less than 30 min in 1-3 days /week and the difference was statistically significant. All the three children with abnormal LVEF were hypertensive and the difference was statistically significant. 6% children were having raised serum cholesterol >190mg/dl.   Serum triglyceride >150mg/dl was observed in 17% obese children. HDL level <20mg/dl was observed in 7% children while LDL above 130mg/dl was observed in 6% children. The proportion among male and female children was comparable. Conclusion: Cardiovascular complications of adulthood in obese children and adolescents may be prevented by early identification and intervention in the form of healthy life style, dietary intake and physical activity.


Author(s):  
Joanna Lewek ◽  
Izabela Jatczak-Pawlik ◽  
Marek Maciejewski ◽  
Piotr Jankowski ◽  
Maciej Banach

IntroductionCoronavirus Disease 2019 (COVID-19) may affect many organs and may be responsible for numerous complications including cardiovascular problems.Material and methodsWe analysed consecutive patients (n=51) admitted to the cardiology department between 1st October 2020 and 31st January 2021 due to symptoms, which might have reflected cardiovascular complications following COVID-19.ResultsThe complications after Covid-19 appeared after 1-4 months after disease recovery.ConclusionsDiabetes, elevated level of CRP and troponin, heart rate variability parameters and worsening of left ventricular ejection fraction are related to the severity of cardiovascular complications following the COVID-19 infection.


2020 ◽  
Vol 47 (2) ◽  
pp. 96-107 ◽  
Author(s):  
Raymundo A. Quintana ◽  
Linh P. Bui ◽  
Rohit Moudgil ◽  
Nicolas Palaskas ◽  
Saamir Hassan ◽  
...  

Speckle-tracking echocardiography has enabled clinicians to detect changes in myocardial function with more sensitivity than that afforded by traditional diastolic and systolic functional measurements, including left ventricular ejection fraction. Speckle-tracking echocardiography enables evaluation of myocardial strain in terms of strain (percent change in length of a myocardial segment relative to its length at baseline) and strain rate (strain per unit of time). Both measurements have potential for use in diagnosing and monitoring the cardiovascular side effects of cancer therapy. Regional and global strain measurements can independently predict outcomes not only in patients who experience cardiovascular complications of cancer and cancer therapy, but also in patients with a variety of other clinical conditions. This review and case series examine the clinical applications and overall usefulness of speckle-tracking echocardiography in cardio-oncology and, more broadly, in clinical cardiology.


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