Heart and Blood Diseases

All Conditions

Cardiomyopathies

Heart Diseases

Antineoplastic Agents

All Drugs and Chemicals

Doxorubicin

Liposomal doxorubicin

Daunorubicin

Survivors of childhood cancer treated with anthracyclines and known to have cardiomyopathy will participate in a 12 week exercise intervention.

Trial of a 12-week period of combined endurance and resistance training in survivors of childhood cancer who were treated with doxorubicin and/or daunorubicin and have impaired cardiac function.

12 Week Exercise Intervention

Daniel Green, MD

This application proposes a prospective, single arm feasibility clinical trial of a 12-week period of combined endurance and resistance training in survivors of childhood cancer who were treated with doxorubicin and/or daunorubicin and have impaired cardiac function.

Baseline and post intervention imaging, laboratory, and neuropsychological evaluations will be used to determine the effects of the intervention on body composition, serum lipid profile, exercise tolerance, and neurocognitive functioning. Participants will be called weekly to monitor compliance with the intervention. Incentives will be given at intervals during the trial to optimize compliance with the intervention.

This study will evaluate the feasibility of a 12-week exercise intervention on the cardiac function of survivors of childhood cancer treated with anthracyclines and known to have cardiomyopathy.

As a secondary objective, the study will document the effect of a 12-week exercise intervention on exercise tolerance, as determined by measurement of peak VO2 and peak exercise workload, shortening fraction, ejection fraction, and left ventricular wall thickness, and assess the impact of the intervention on neurocognitive functioning in survivors of childhood cancer treated with anthracyclines and known to have cardiomyopathy.

Resistance and Aerobic Exercise for Subclinical Anthracycline Cardiomyopathy

St. Jude Children's Research Hospital

Heart Failure

Patients receive hMSCs IV over 10-20 minutes on days 1, 14, 21, and 28 and standard of care treatment for heart failure in the absence of disease progression or unacceptable toxicity.

Patients receive hMSCs transendocardially for a total of 15 injections and standard of care treatment for heart failure in the absence of disease progression or unacceptable toxicity.

Patients receive standard of care treatment for heart failure.

Best Practice

Laboratory Biomarker Analysis

Mesenchymal Stem Cell Transplantation

Amanda Olson, MD

This randomized pilot phase I trial studies the side effects of donor bone marrow derived mesenchymal stem cells in controlling heart failure in patients with cardiomyopathy caused by anthracyclines. Donor bone marrow derived mesenchymal stem cells may help to control symptoms of heart failure and improve heart function.

PRIMARY OBJECTIVE:

I. To demonstrate the safety of allogeneic human mesenchymal stem cells (hMSCs) administered by intravenous infusion and transendocardial injection in patients with left ventricular (LV) dysfunction and heart failure secondary to chemotherapy with anthracyclines.

SECONDARY OBJECTIVE:

I. To demonstrate the efficacy of allogeneic hMSCs administered by intravenous infusion and transendocardial injection in patients with left ventricular dysfunction (left ventricular ejection fraction \[LVEF\] \< 40%) and heart failure secondary to treatment with anthracyclines.

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM I: Patients receive hMSCs intravenously (IV) over 10-20 minutes on days 1, 14, 21, and 28 and standard of care treatment for heart failure in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive hMSCs transendocardially for a total of 15 injections and standard of care treatment for heart failure in the absence of disease progression or unacceptable toxicity.

ARM III: Patients receive standard of care treatment for heart failure.

After completion of study treatment, patients are followed up periodically.

Donor Bone Marrow Derived Mesenchymal Stem Cells in Controlling Heart Failure in Patients With Cardiomyopathy Caused by Anthracyclines

Randomized 3-Arm Trial With Standard of Care Alone vs Either Intravenous Infusion or Transendocardial Injection of Allogeneic Bone Marrow Derived Multipotent Mesenchymal Stromal Cells (MSCs) Plus Standard of Care in Patients With Anthracycline-Associated Cardiomyopathy

Statistical analyses of safety will be descriptive.

The comparison will be between the two groups of patients.

As regards statistical analyses, the results of the trial will be displayed in table format. Will provide confidence intervals of the differences in change from baseline between each investigational group and the control group. If both investigation groups are significant at the p \< .05 level, then the two investigational drugs can be compared using a gatekeeping procedure. These intervals and the associated p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Symptoms and General Pathology

Substance Related Disorders

Wounds and Injuries

Cardiotoxicity

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

Radiation Injuries

Lana J Dixon, MB BCh BAO

Anthracyclines treat up to 60% of childhood malignancies with remarkable improvements survival rates. Unfortunately anthracyclines are associated with an increased cardiomyopathy risk. One study showed an almost six-fold greater risk of developing cardiomyopathy compared to sibling controls. A retrospective pilot study showed evidence of subclinical dysfunction (including impaired global longitudinal strain) in 42/52 childhood cancer survivors. There is limited research in this area, therefore current guidelines are based on expert opinion alone and lack consensus. Current methods of detection diagnose cardiomyopathy at an irreversible stage i.e. when the compensatory mechanisms are exhausted and the left ventricular ejection fraction impaired. Small trials have shown that early treatment with standard heart failure therapy may reverse damage, further validation is however required in this cohort.

Newer techniques such as tissue doppler and strain rate imaging have shown promise for early prediction of cardiomyopathy in adult studies. Biomarkers such as troponin and NT-proBNP have also shown a correlation with cardiomyopathy.

This study (n=208) aims to use echocardiography, strain imaging, holter monitoring and MRI for early detection of cardiomyopathy. Biomarkers, both currently used (for example, troponin and NTproBNP,) and more novel (for example, IL6, MPO, and sST2) will be assessed to see if early cardiomyopathy can be predicted.

This study will explore biomarker discovery by analysing an age/gender matched subgroup for the top differentially expressed microRNA and protein biomarkers. Selected biomarkers will then be validated in a larger cohort.

CLINICAL APPOINTMENT A linked anonymised Case Report Form will be completed using participant answers and relevant aspects of their electronic care record. This will involve questions about the patient's demographics, chemotherapy history, cardiac symptoms, past medical history, medication history and family history.

Consenting patients will then have

* height, weight and blood pressure taken
* cardiovascular and respiratory examination Participants will then undergo
* SF36 quality of life questionnaire
* 6 minute walk test, grip strength
* Electrocardiogram by a trained researcher
* Venesection- 40ml blood sample from a peripheral vein by the trained researcher Crevicular fluid sample

INVESTIGATIONS

Participants will be invited for:

1. 24 hour holter monitor- arrhythmia assessment
2. Echocardiogram- diastolic and systolic function assessment, valvular analysis, global longitudinal strain
3. Magnetic resonance imaging (MRI) scan of the heart- volumetric analysis, late gadolinium enhancement and STIR imaging assessments. As part of the scan the patient will require a venflon to be inserted into a peripheral vein for gadolinium injection. A safety questionnaire will be sent to the patient prior to attendance as part of standard MRI procedure. All safety aspects will be re-assessed on the day of attendance by a trained radiographer

BLOOD SAMPLE ANALYSIS Blood samples will be sent for standard of care and cardiovascular risk assessment. Tests include a full blood picture, urea and electrolytes, C-reactive protein, iron profile, B12 and folate, lipid profile, HbA1c, NT-proBNP and high sensitivity troponin.

Additional disease associated biomarkers for example sST2, MPO, and IL6 will be quantified using immunoassays. Biomarker discovery, including transcriptomics and proteomics will be carried out to identify signatures that could predict cardiotoxicity, subclinical dysfunction, and cardiomyopathy.

Blood samples will be collected for currently used (for example troponin, NTproBNP,) and novel (for example, IL6, MPO, and sST2) biomarkers to see if we can predict early cardiomyopathy. Transcriptomics and proteomics based biomarker discovery will identify new biomarkers to allow timely diagnosis.

Late Anthracycline Induced Cardiotoxicity- Childhood Cancer Survivors

Early Detection of Late Anthracycline Induced Cardiotoxicity in Survivors of Childhood Malignancy

Number of participants with anthracycline related cardiotoxicity as defined by the British Society of Echocardiography and British Cardio-Oncology Society guidelines

Levels of high sensitivity troponin T and NT-proBNP

Queen's University, Belfast

Senior Lecturer

Rare Diseases

Myocarditis

Immune Checkpoint Inhibitors

Immunomodulating Agents

Christian Houbois, MD

Navpreet Sekhon, MB Bch BAO

Patients undergoing dual treatment with Immune checkpoint inhibitors (ICI) for various cancers, e.g. melanoma, are at increased risk of developing myocarditis and cardiomyopathy. Currently, only limited data on serial myocardial tissue changes during treatment and whether they predict outcomes are available. Cardiac MRI (CMR) is the reference standard for non-invasive myocardial volumes/function analysis and uniquely characterizes myocardial tissue. Therefore, it may help detect myocardial tissue changes during treatment and help early treatment and prevent adverse cardiac outcomes.

As patients going through cancer therapy live longer, they are at a higher risk of developing cardiovascular disease. Hence the evolving field of Cardio-Oncology has garnered much attention and importance. In recent years, immune checkpoint inhibitors (ICI) have become an essential component of cancer therapy, significantly improving patient outcomes that were previously considered palliative, e.g. metastatic melanoma, renal cell or lung cancer, and these therapies have improved survival.

With ICI therapy and especially with combination therapy, patients may develop severe ICI-related adverse events, e.g. myocarditis (1-5%) which is fatal in 30-50% of the patients. Another more significant subgroup of patients will develop non-inflammatory cardiomyopathy or other major cardiac events like cardiovascular death, cardiac arrest etc. There is also evidence that during ICI treatment atherosclerotic disease may progress. Identifying patients at risk for both remains a major challenge and is a knowledge gap in Cardio-Oncology.

Cardiovascular magnetic resonance (CMR) is a unique, highly reproducible, multiparametric method for non-invasive myocardial tissue characterization for diagnosing myocardial inflammation. Biomarkers like quantitative cardiac relaxometry (T1/T2-Mapping) with extracellular volume fraction (ECV), delayed gadolinium enhancement (LGE) or myocardial strain show insights into myocardial tissue composition. These biomarkers have the potential to identify early myocardial changes before the risk of clinical myocarditis or non-inflammatory cardiomyopathy occurs and may therefore help identify early myocardial tissue changes during ICI treatment and help identify patients at risk early on. Also, CMR can assess the aorta with high temporal and spatial resolution to identify atherosclerotic changes.

Only a few retrospective studies and case reports with small numbers of patients have investigated ICI-related cardiac events during treatment. Evidence shows that many patients present with heart failure (\~80%), but troponin is only elevated in \~45%. This indicates that ICI-associated left ventricular (LV) dysfunction may exist without troponin elevation. Other data suggests that the ICI-associated myocardial tissue inflammation pattern might differ from viral myocarditis. The myocardial T1/T2 relaxation times may be elevated during ICI-associated myocardial inflammation. There is also evidence that strain changes are associated with adverse events within 30 days of treatment. However, all these studies demonstrate CMR findings when patients have already developed LV dysfunction or myocarditis. The proposed project would be the first prospective study to get deeper insights into serial, systematic ICI-associated myocardial tissue changes during treatment and their correlation with serum biomarkers and clinical symptoms.

Immune Checkpoint Inhibitor Therapy for Cancer and Risk of Myocarditis or Cardiomyopathy

Association of Immune Checkpoint Inhibitor Therapy for Cancer With Early Myocardial Tissue and Biomarker Changes During Treatment - Implication for Risk of Myocarditis and Cardiomyopathy

No plan to share individual participant data with other researchers.

The following parameters are investigated to assess for underlying myocardial remodelling and/or inflammation during treatment with ICI.

Left ventricular volumes in ml Left ventricular ejection fraction in percentage T1 Mapping: T1 relaxation time in milliseconds T2 Mapping: T2 relaxation time in milliseconds ECV = (1-hematocrit) × (Δ(1/T1myocardium)/Δ(1/T1blood)) in percentage Strain (GCS, GLS, GRS) reported as a percentage, formula =(Max Length-Initial Length)/Initial Length LGE is qualitatively described as categorical variables e.g. epicardial, mid-myocardial, subendocardial or transmural.

LGE is quantified as mass in gram and as percentage of the LV mass. High sensitivity troponin 1 nanogram/ mL B-type natriuretic peptide (BNP) nanogram/L High sensitivity CRP in mg/L

This analysis is to determine if the biomarkers are associated with LVEF changes over time.

Left ventricular volumes in ml Left ventricular ejection fraction in percentage T1 Mapping: T1 relaxation time in milliseconds T2 Mapping: T2 relaxation time in milliseconds ECV = (1-hematocrit) × (Δ(1/T1myocardium)/Δ(1/T1blood)) in percentage Strain (GCS, GLS, GRS) reported as a percentage, formula =(Max Length-Initial Length)/Initial Length LGE is qualitatively described as categorical variables e.g. epicardial, mid-myocardial, subendocardial or transmural.

LGE is quantified as mass in gram and as percentage of the LV mass.

This analysis is to determine if blood biomarkers are associated with LVEF changes over time.

High sensitivity troponin 1 nanogram/ mL B-type natriuretic peptide (BNP) nanogram/L High sensitivity CRP in mg/L

Sunnybrook Health Sciences Centre

Assistant Professor, MD

Neoplasms

Skin and Connective Tissue Diseases

Breast Neoplasms

Neoplasm Metastasis

Breast Diseases

Skin Diseases

Doxorubicin Induced Cardiomyopathy

Tochi Okwuosa, DO, FACC

This study looks to find a causative or predictive aspect of the suPAR biomarker for heart failure in breast cancer patients receiving Doxorubicin drug chemo regimen.

suPAR is a circulating protein which can be found in blood and/or urine and is associated with both kidney and heart disease.

* Hypothesis 1: Higher suPAR at baseline will predispose to Doxorubicin-induced cardiomyopathy or heart failure, observed by histology (under the microscope and other lab techniques) in mouse models, and tested using heart ultrasound techniques in humans.
* Hypothesis 2: suPAR is a marker of Doxorubicin-induced cardiomyopathy or heart failure after exposure to Doxorubicin, observed by histology (under the microscope and other lab techniques) in mouse models, and tested in humans.

The study will look at suPAR's association with three other biomarkers called troponin, B-Type Natriuretic Peptide (BNP) and C- Reactive Protein (CRP) that are also associated with heart disease.

In this study, the patient will have blood drawn as a routine part of the cancer treatment. That is prior to starting the cancer therapy, then after the first 2 and last 2 doxorubicin cycles (4 cycles altogether); as well as at 3, 6, \& 12 months after doxorubicin treatment. (6 Visits in total) The patient will also have an echocardiogram (echo, heart ultrasound) at each of these time points. The first of the six study echos is considered part of the routine care.

* Hypothesis 1: Higher suPAR at baseline will predispose to DOX-induced cardiomyopathy to be observed by histology in mouse models, and tested using LVEF (Left Ventricular Ejection Fraction) assessment, and surrogate cardiovascular outcome measures as described in humans.
* Hypothesis 2: suPAR is a marker of DOX-induced cardiomyopathy after exposure to DOX, to be observed by histology in mouse models, and tested using surrogate cardiovascular outcome measures as described in humans.

  1. Patients meeting outlined eligibility criteria are identified by breast cancer physicians working in the Rush Cancer Center. After eligibility is verified, patients are approached by the study coordinators or research fellow to discuss participation in the trial while patients were being seen by their provider within the cancer center and given the informed consent form for review. Patients are contacted approximately one week later to answer questions and plan for baseline visit if interested in enrolling.
  2. After signing the informed consent form, patients are officially enrolled. The research nurse, study coordinator, or research fellow will conduct research visits at each of the six study time points outlined in the protocol: pre-chemo, post-2 cycles of doxorubicin, post-4 cycles of doxorubicin, 3 months post-doxorubicin, 6 month post-doxorubicin and 12 months post-doxorubin
  3. Each study visit consists of collecting lab work via blood draw as detailed in the protocol as well as an echocardiogram performed with strain.
  4. Results from each test are collected, reviewed by the PI and documented in the patient's study binder.
  5. Preliminary human results have not been analyzed at this time as there is currently insufficient data collected.

In the laboratory approach of the study, the investigators aimed to establish the role of suPAR in DOX induced cardiomyopathy. The risk for DOX induced cardiomyopathy is known to increase with an increase of the accumulative dose. The investigators therefore used two doses of DOX. One group of mice received weekly injections of DOX at 3mg/kg bodyweight for 6 week (accumulative dose of 18mg/kg: DOX18) whereas another group received an accumulative dose of 25mg/kg bodyweight (DOX25: 5 weeks, at 5 mg/kg bodyweight). Blood samples were taken before the first injection, in the middle of treatment and at the end of treatment or at the day of sacrifice. The bodyweight of the animals was constantly monitored throughout the study.

At time of sacrifice, the heart weight and tibia length of the mice were quantified and cells were isolated to determine cellular levels of reactive oxygen species (ROS), contractility and Ca handling properties.

DOX induced cardiomyopathy can manifest years after treatment. Tissue samples from hearts of the DOX18 and DOX25 treatment group were obtained and quantitative PCR (Polymerase Chain Reaction amplification) of the ventricular tissue will help us determine the changes in protein expression and cellular signaling that underlie these DOX induced changes in cellular function.

Blood samples obtained from the DOX18 and DOX25 mice will be analyzed for their level of suPAR to determine changes in suPAR over the duration of treatment and potential correlations of \[suPAR\] with the degree of cardiac dysfunction.

The data collected will be analyzed using a descriptive analysis with means and standard deviations for continuous variables and percentages for categorical variables. A paired t-test comparing the pre-post difference will be used to compare the differences in the groups comparing pre to post measures of myocardial damage based on histology for mouse models, and LVEF (Left Ventricular Ejection Fraction) for human data. Analysis will be performed using SAS (statistical analysis software).

The expected results from the data collected in this study aim to both gain an understanding of and describe the relationship of various covariates to primary outcomes.

It is expected to have 50 participants by the study end date. There is a trained team working on the study, insuring quality of data gathering, recruitment and enrollment of patients.

Blood samples are put in a Centrifugation machine to separate the plasma. The plasma is then kept in -70 to -80 degrees Fahrenheit. Each sample will be studied for suPAR levels.

The Role of suPAR Biomarker in Blood Samples of Breast Cancer Patients During and Post Doxorubicin Chemotherapy: Causative vs. Predictor

The Role of suPAR in Doxorubicin Induced Cardiomyopathy in Breast Cancer Patients: Causative vs. Predictor

A blood draw will be done at baseline for all participants. The blood samples will be processed by Centrifugation, to separate the plasma, and the suPAR level measured using ELISA technique, to stratify the participants that have a higher or normal baseline.

Although there is no current consensus regarding normal suPAR blood level, a level of 3000 pg/mL is considered a high level.

Higher baseline blood level of suPAR, will predispose patients with breast cancer undergoing chemo regimen containing doxorubicin, to develop heart toxicity (heart failure or cardiomyopathy).

Heart failure or Cardiomyopathy will be diagnosed by the clinical evaluation with signs and symptoms, LVEF (Left Ventricular Ejection Fraction) with echocardiograms (heart ultrasound), and surrogate cardiovascular outcome measures as described in humans, and tissue visualization and histology in mouse models, with various staining techniques, whether it was H\&E staining, or other immunological staining.

A blood draw will be done at baseline for all participants. The blood samples will be processed by Centrifugation to separate the plasma, and the suPAR level measured using ELISA technique, to stratify the participants having a higher or normal baseline.

Although there is no current consensus regarding normal suPAR blood level, a level less than 3000 pg/mL is considered a normal level.

A normal baseline blood level of suPAR, with progressive elevation following doxorubicin exposure, along with other blood markers for heart failure, will be considered as a predictive marker for doxorubicin-induced cardiomyopathy.

Heart failure or Cardiomyopathy will be diagnosed by the clinical evaluation with signs and symptoms, LVEF (Left Ventricular Ejection Fraction) with echocardiograms (heart ultrasound), and surrogate cardiovascular outcome measures as described in humans, and tissue visualization and histology in mouse models using H\&E staining, or other immunological staining techniques.

Rush University Medical Center

Tochukwu M. Okwuosa, DO, FACC, Assistant Professor of Medicine and Cardiology, Director of Cardio-Onc Services, Principal Investigator in the suPAR pilot study.

Pheochromocytoma

Paraganglioma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Paragangliomas 1

Neuroendocrine Tumor

Neuroepithelioma

Vasoconstrictor Agents

Respiratory System Agents

Antihypertensive Agents

Epinephrine

Racepinephrine

Epinephryl borate

Patients included in this cohort (n=50) are those who are diagnosed of Pheochromocytoma / Paraganglioma, willing to consent for the study and not on α-blockade at the time of recruitment into study, while can be on any other anti hypertensives

Patients in this group, besides the usual evaluation of Pheochromocytoma / Paraganglioma, will also undergo detailed cardiac and vascular evaluation, which will be done at diagnosis, at 7- 10 days of α-blockade, and 7 days, 3 and 6 months post adrenalectomy/ Paraganglioma excision The cardiovascular evaluation includes 2D-echocardiography, speckle tracking Echo (for measuring global longitudinal strain), serum NT-proBNP estimation and flow mediated vasodilatory studies by Doppler Ultrasonography of the brachial artery to assess the endothelial dependent and smooth muscle dependent vasodilatory responses

This is a contemporary age- and gender-matched control group This group includes 10 newly detected (within 3 months) Essential Hypertensive patients, who will undergo treatment with standard anti- HT medications Cardiac evaluation will be done at baseline and after 3 months of anti hypertensive medications

This is a contemporary age- and gender-matched control group This group includes 10 Healthy individuals (normal in physical examination, ECG , Echo), that include hospital staff nurses, technicians, doctors whom would be requested to volunteer Cardiac evaluation will be done at the start of study and after 6 months

Observational study

Gaurav Agarwal, MS,DNB,PDC

PHEOCHROMOCYTOMA (PCC)/ PARAGANGLIOMA are catecholamine secreting tumors with varied manifestations. Besides hypertension, PCC patients may have subclinical to overt cardiac and vascular dysfunction, which are important to recognize to minimize perioperative morbidity and mortality. Cardiovascular (CV) dysfunction can be in the form of hypertension, left ventricular (LV) hypertrophy, heart failure, cardiomyopathy, dysrhythmias, angina and Myocardial infarction. Literature search revealed a few retrospective and a few prospective studies, including one prospective follow up study conducted at SGPGIMS to document CV changes in PCC. Our institutional study was the first to document the nature and extent of CV dysfunction and cardiomyopathy and their reversal after surgical cure. The studies revealed that PCC patients had significantly higher LV mass index, higher LV diastolic dysfunction, subclinical impaired LV systolic function. Earlier studies postulated apparent improvement in various cardiac indices even with selective α-blockade and continued after surgical cure, with near normalization at 3 -6 months postoperatively. Detailed cardiac and vascular evaluation in PCC patients can be of help in preoperative optimization of cardiac risk and may provide prognostic information The literature on PCC-mediated CV dysfunction and catecholamine cardiomyopathy is largely limited to case reports and retrospective studies, with few reports of their reversal after curative PCC operations. Whether the duration of disease influence the function of heart was not apparently addressed in earlier trials. Trials that established the differences in the degree of cardiac dysfunction between normotensive and hypertensive PCC patients involved smaller proportion of study subjects. Sub clinical changes in endomyocardium was presumed but not objectively assessed and hence its reversal after surgical cure is uncertain.

The aim of this research is to study the cardiac and vascular changes in Pheochromocytoma/ Paraganglioma patients and their reversal following curative surgery

The aim of this research is to study the cardiac and vascular changes in Pheochromocytoma/ Paraganglioma patients and their reversal following curative surgery

This prospective, case-control study is conducted at SGPGIMS, Lucknow, India, tertiary care referral institute, between January 2019 and September 2021 after approval from institutional ethics committee. The study group includes 50 biochemically and histopathology proven PCC /Paraganglioma patients, who after 1 to 3 weeks of α-adrenoceptor blockade with oral prazosin undergo primary laparoscopic or open surgery. Cure of hypercatecholaminism will be documented by normal 24-hour urinary fractionated metanephrine values at 7-10 days postoperatively.

Two contemporary age- and gender-matched control groups includes 10 newly detected (withtin 3 months) Essential Hypertensive (E-HT) patients, who will undergo treatment with standard anti- HT medications and 10 Healthy individuals (normal in physical examination, ECG , Echo), that include hospital staff nurses, technicians, doctors whom would be requested to volunteer.

METHODOLOGY

Patients in the study group, besides the usual evaluation of PCC, also undergo detailed cardiac and vascular evaluation, at diagnosis, at 7- 10 days of α-blockade, and 7 days, 3 and 6 months post adrenalectomy/ Paraganglioma excision and in control groups - E-HT controls, cardiac evaluation is done at diagnosis and after 3 months of anti HT medications ; in Healthy individuals, cardiac evaluation is done at the start of study and after 6 months.

The CV evaluation includes 2D-echocardiography, speckle tracking Echo (for measuring global longitudinal strain), serum NT-proBNP estimation and flow mediated vasodilatory studies by Doppler Ultrasonography of the brachial artery to assess the endothelial dependent and smooth muscle dependent vasodilatory responses

Cardiac and Vascular Changes in Pheochromocytoma and Paraganglioma

Prospective Cohort Study of Objective Cardiac and Vascular Changes in Pheochromocytoma and Paraganglioma and Their Reversal Following Curative Surgery

Left ventricle end systolic and end diastolic diameter in millimeter

Left ventricle end systolic and end diastolic volume dimensions in milliliter

Left ventricle Ejection fraction by Simpsons method in percentage

Peak velocities of the early (E) and Late phase (A) of the mitral valve inflow pattern and their ratio in centimeter per second

Flow rate across mitral valve in centimeter per second and deceleration time in millisecond

Left ventricle global longitudinal strain in percentage

Left ventricle global circumferential strain in percentage

Flow mediated dilation of brachial artery diameter pre and post sublingual isosorbide dinitrate in millimeter

Sanjay Gandhi Postgraduate Institute of Medical Sciences

Professor of Endocrine Surgery

Blood and Lymph Conditions

Immune System Diseases

Lymphoma

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

NTproBNP will be monitored serially prior to start of anthracycline based chemotherapy, at each cycle of anthracycline based chemotherapy, and at 3 month intervals for a total of 12 months.

Clinical, echocardiographic, and biomarker data will be collected on all patients at baseline and at standardized intervals at 3, 6, 9, and 12 months following initiation of Anthracycline chemotherapy.

NTproBNP will not be monitored while patients are on study unless clinically indicated. Clinical, echocardiographic, and biomarker data will be collected on all patients at baseline and at standardized intervals at 3, 6, 9, and 12 months following initiation of Anthracycline chemotherapy. Biomarker data will also be collected at each cycle of Anthracycline chemotherapy.

NTproBNP above the upper limit of normal will trigger the initiation of heart failure therapy with counseling from a study investigator based on protocol specified algorithm.

Biomarker Guided Intervention

Bonnie Ky, MD, MSCE

Investigators will evaluate the safety and feasibility of a biomarker-guided cardioprotection strategy using NTproBNP, as compared to usual care, in breast cancer and lymphoma patients treated with anthracyclines.

This is a randomized, open-label pilot trial of a biomarker-guided strategy using NT-proBNP to identify and treat patients with a high risk of cancer therapy-related cardiotoxicity. Patients will be enrolled and randomized prior to initiation of anthracycline-based therapy and followed for 12 months with blood samples, echocardiography, and patient reported outcomes surveys. The overall hypothesis is that a biomarker guided treatment strategy that initiates neurohormonal antagonists in breast cancer or lymphoma patients who have increases in NT-proBNP prior to, during, or after anthracyclines will be feasible, well-tolerated, and result in attenuation of cardiotoxicity, compared to standard care.

Serial monitoring of NTproBNP during chemotherapy will be used to identify high-risk patients in the intervention arm; patients who experience elevations in NTproBNP will be initiated and titrated on a personalized regimen of neurohormonal antagonists. Patients in the usual care arm will not have serial NTproBNP monitoring and will be managed according to usual care.

Pilot Study of an NTproBNP Guided Strategy of Cardioprotection

A Randomized, Open Label Pilot Trial of a Biomarker Guided Strategy of Cardioprotection in Patients With Lymphoma or Breast Cancer Treated With Anthracyclines

Change in global longitudinal strain by echocardiogram

Change in circumferential strain by echocardiogram

Change in hsTnT measured in batches from banked samples

Change in GDF-15 measured in batches from banked samples

Change in MPO measured in batches from banked samples

Change in NTproBNP measured in batches from banked samples for all patients on both arms

Change in total weekly leisure activity in METS (assessed by GODIN Leisure Time Exercise Questionnaire)

Change in MD Anderson Symptoms Inventory - Heart Failure (MDASI-HF). Higher scores indicate increased symptom severity or symptom distress.

Change in Patient Reported Outomes Information System (PROMIS) Fatigue Score. A higher score corresponds to higher levels of reported fatigue.

Change in Patient Reported Outomes Information System (PROMIS) Global Health score. Higher scores indicate a healthier patient.

Change in NCI Patient Reported Outcomes - Common Terms and Criteria for Adverse Events (PRO CTCAE).

Incidence of anthracycline chemotherapy being held or discontinued secondary to side effects or toxicity

percent of eligible patients who are randomized

percent of randomized patients who complete the study per protocol

percent of study activities completed in window

Compliance by PROMIS Scale v1.0 for patients in the biomarker guided arm initiated on heart failure medications

Maximum tolerated dosage of neurohormonal antagonist medications for patients in the biomarker-guided arm with NTproBNP above upper limit of normal

Rate of Grade 2 or higher adverse events by CTCAEv5.0

Change in clinically measured NTproBNP following initiation of neurohormonal antagonists in patients with NTproBNP above upper limit of normal in the biomarker guided arm

Change in core-lab quantitated left ventricular ejection fraction

Incidence of cardiotoxicity defined as LVEF decline of at least 10% to less than 50%

Incidence of new or worsened clinical heart failure, defined as urgent or new office or emergency department visit or hospitalization for HF, adjudicated by a clinical events committee

Frequency of cancer treatment interruptions due to cardiotoxicity

National Heart, Lung, and Blood Institute (NHLBI)

Abramson Cancer Center at Penn Medicine

Digestive System Diseases

Stomach Neoplasms

Leukemia

Stomach Cancer

Patients will participate in a 10 week outpatient cardiac rehabilitation program. Exercise will consist of 3 days per week of interval training on a treadmill or bike at an intensity between 50-90% of heart rate reserve. Additionally patients will perform resistance exercises 1-2 days per week and attend 8 nutrition and lifestyle classes.

Control group will not be instructed on exercise, but encouraged to follow standard medical advice.

Intervention will include 10 weeks of a standard cardiac rehabilitation program consisting of thrice a week aerobic exercise and 1-2 days per week resistance exercises.

Exercise

The purpose of this study is to identify patients at risk for future heart failure using novel markers of early cardiac damage and determine if exercise training can improve these emerging markers as well as overall fitness and quality of life.

With more than 14 million cancer survivors in the United States, more patients than ever are living well beyond their initial cancer diagnosis. However despite the tremendous progress, cancer treatments often come with adverse side-effects, perhaps none are more serious or devastating than chemotherapy induced heart failure.

In many patients, the clinical manifestation of heart failure may not appear until a year, or several years, after completion of chemotherapy. While an echocardiogram is part of standardized surveillance for patients on these drugs, current echocardiogram parameters may not be sensitive enough to quickly detect early heart damage which, in some cases, is irreversible.

Unfortunately, even if detected early, there is no uniformity in terms of how to best treat patients with subclinical cardiac dysfunction who are at risk for heart failure. The use of certain blood pressure drugs show promise, especially in patients with hypertension. However, in addition to drug side-effects (e.g. dizziness/lightheadedness), they do not target the underlying mechanism of chemotherapy induced cardiotoxicity.

Exercise, in various forms, has shown promise in animal studies as a potential cardio-protective therapy to counteract drug toxicity. In general, exercise has many pleiotropic effects for patients receiving chemotherapy (e.g. reduces fatigue, improves endurance, reduces frailty, and enhances quality of life). Relative to DOX toxicity, research involving animals has also shown that exercise protects against deleterious heart dysfunction while showing an enhancement of potential mechanisms involved in chemotherapy induced heart failure (i.e. anti-oxidant and anti-apoptosis pathways).

Patients with cancer who receive either doxorubicin (DOX) or trastuzumab will be screened by one of two methods: 1) a strain echo or 2) a high sensitivity troponin. If either test is positive, patients will meet with a board-certified cardiologist who will determine if the patient may participate in the exercise trial. Under the supervision of a trained clinical exercise physiologist patients will undergo baseline testing, which includes: a quality of life assessment via questionaires, a body composition test, cardiopulmonary stress test and a muscle strength test. These assessment will be performed at baseline and at 12 weeks. Also performed at 12 weeks will be a repeat strain echo and high sensitivity troponin.

Following baseline testing patients will be randomized into exercise training versus standard care. The exercise training will include 12 weeks of cardiac rehabilitation which can be offered in Detroit, Livonia, or West Bloomfield. Exercise will consist of 3 days per week of an interval training aerobic exercise on a treadmill and/or bike for 30-60 minutes and 1-2 days per week of an individualized resistance training program.

Prevention Using Exercise Rehabilitation to Offset Cardiac Toxicities Induced Via Chemotherapy

Spectral Doppler measure with General Electric software analysis of global longitudinal strain.

During a graded treadmill test, breath-by-breath sampling of expired air will be measured using a MGC Diagnostics gas exchange analysis system.

Body fat will be analyzed using air displacement plethysmography (BodPod/Cosmed)

Peak torque will be measured using the Biodex Isokinetic dynamometer.

Quality of life will be assessed using the Functional Assessment of Cancer Therapy (FACT-G).

High sensitivity cardiac troponin will be analyzed using a commercial immunoassay.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Resistance and Aerobic Exercise for Subclinical Anthracycline Cardiomyopathy	NCT01071473	Cardiomyopathy	12 Week Exercis...	18 Years -	St. Jude Children's Research Hospital
Donor Bone Marrow Derived Mesenchymal Stem Cells in Controlling Heart Failure in Patients With Cardiomyopathy Caused by Anthracyclines	NCT02962661	Cardiomyopathy Heart Failure Hematopoietic a... Malignant Solid...	Best Practice Laboratory Biom... Mesenchymal Ste... Mesenchymal Ste...	18 Years - 80 Years	M.D. Anderson Cancer Center
Late Anthracycline Induced Cardiotoxicity- Childhood Cancer Survivors	NCT04852965	Anthracycline I...		18 Years -	Queen's University, Belfast
Immune Checkpoint Inhibitor Therapy for Cancer and Risk of Myocarditis or Cardiomyopathy	NCT06309862	Cardio-Oncology Cardiomyopathy ...		18 Years -	Sunnybrook Health Sciences Centre
The Role of suPAR Biomarker in Blood Samples of Breast Cancer Patients During and Post Doxorubicin Chemotherapy: Causative vs. Predictor	NCT03505164	Doxorubicin Adv... Cardiomyopathie... Breast Cancer		18 Years - 64 Years	Rush University Medical Center
Cardiac and Vascular Changes in Pheochromocytoma and Paraganglioma	NCT05082311	Pheochromocytom... Paraganglioma Cardiovascular ...	Observational s...	7 Years -	Sanjay Gandhi Postgraduate Institute of Medical Sciences
Pilot Study of an NTproBNP Guided Strategy of Cardioprotection	NCT04737265	Cardiotoxicity Toxicity Due to... Breast Cancer Lymphoma Cardiomyopathie... Heart Failure	Biomarker Guide...	18 Years -	Abramson Cancer Center at Penn Medicine
Prevention Using Exercise Rehabilitation to Offset Cardiac Toxicities Induced Via Chemotherapy	NCT02796365	Doxorubicin Ind... Breast Cancer Gastric Cancer Leukemia	Exercise	18 Years - 75 Years	Henry Ford Health System
Early Assessment of Cardiac Function After Treatment With CAR-T Cells	NCT06350994	Car T- Cell Hematologic Mal... Acute Lymphobla... Lymphoma, B-Cel... Multiple Myelom...		18 Years -	Assistance Publique - Hôpitaux de Paris
Stem Cell Injection in Cancer Survivors	NCT02509156	Cardiomyopathy ...	Allo-MSCs Placebo	18 Years - 79 Years	The University of Texas Health Science Center, Houston

Spots Global Cancer Trial Database for cardiomyopathy