Heart and Blood Diseases

All Conditions

Symptoms and General Pathology

Coronary Artery Disease

Syndrome

Necrosis

Myocardial Ischemia

Arteriosclerosis

Systemic Inflammatory Response Syndrome

Coronary Disease

Ischemia

Arterial Occlusive Diseases

Vascular Diseases

Inflammation

Shock

Heart Diseases

Cell saver intraoperatively for coronary artery bypass grafting using cardiopulmonary bypass

Cell saver

Conventional suction for coronary artery bypass grafting using cardiopulmonary bypass

No cell saver

Sune Damgaard, MD

Daniel A Steinbrüchel, Professor

Cardiac surgery using heart and lung machine produces an inflammatory reaction in the body. This leads in few percent of cases to heart, lung, and kidney disturbances that potentially causes death. White blood cells in contact with the heart and lung machine and external surfaces release mediators partly responsible for this. Blood collected by the suction and the blood remaining in the heart and lung machine after its use, can be cleaned by a cell saver before reinfusion, and this might reduce the inflammatory response.

Introduction

Cardiopulmonary bypass (CPB) during cardiac surgery induces in all patients a systemic inflammatory response syndrome (SIRS) that is more pronounced than for other surgical procedures. Depending on the severity of this, myocardial dysfunction, respiratory failure, renal and neurological dysfunction, coagulation disturbances and impaired liver function might follow. In worst cases this leads to acute respiratory distress syndrome, disseminated intravascular coagulation, multi organ failure, shock and death. The cause is besides the surgical trauma, the passage of the blood through the extra corporal circulation (ECC) and its pumps and oxygenator, hemodilution, hypothermia, heparin and protamine administration, ischemia and reperfusion, and endotoxemia (LPS) as a cause of intestinal ischemia. The ECC is the main cause of immunological activation and leads in severe cases to the so-called post-perfusion syndrome. This is characterised by increased capillary permeability and intercellular fluid, peripheral vasoconstriction, fever, myocardial edema, diffuse cerebral edema and diffuse hemorrhagic diathesis. This syndrome is considered to be a more severe form of SIRS. Even though most patients have no sequelae after CPB, all patients must be considered to be influenced, in varying degree, by SIRS. High levels of pro-inflammatory cytokines (interleukin (IL)-6, IL-8, IL-1a, IL-1b, tumor necrosis factor (TNF) alfa), have generally been associated with adverse events after CPB. Of importance is also LPS from gram-negative intestinal bacteria, translocating to the systemic circulation during ischemia.

Hypothesis

Cleansing of suction blood and the remaining blood in the ECC after termination of CPB, reduces the load of inflammatory cells and mediators in the patients' circulation. This potentially diminishes SIRS with a reduction in postoperative organ dysfunction and morbidity.

Aim

To cleanse suction blood and the remaining blood in the ECC after termination of CPB by means of a cell saver and monitor the influence on inflammatory mediators and the potential clinical benefits.

Outcome measures

Primary: Concentrations of IL-1B, IL-6, IL-8, IL-10, IL-12p70, TNFa, TNF-R1, TNF-R2, PCT and LPS in patient blood: 6, 24 and 72 hours after termination of CPB.

Secondary: Bleeding, need for allogenic blood transfusions and blood products and clinical effect focusing on known complications to cardiac surgery and CPB.

Design

Prospective randomised clinical trial including 40 patients planned for on-pump coronary artery bypass grafting (CABG). n=20 in the trial group (use of cell saver) and n=20 in the control group (no cell saver). No patients receive postoperative autotransfusion of drain blood.

Sample size

Estimation based on comparable studies.

Anaesthesia and surgery

In accordance with current guidelines of the clinic, this includes prophylactic antibiotics (cefuroxime and gentamycin). Cell saver: Medtronic Autolog.

Patient exclusion during the trial

Patients are excluded in cases of autotransfusion of blood not cleansed by the cell saver, for instance in cases of major blood loss.

Cleansing of Suction Blood in Cardiac Surgery for Reduced Inflammatory Response

Does Cleansing of Suction Blood During Cardiac Surgery With Heart and Lung Machine Reduce the Postoperative Inflammatory Response ?

Danish Heart Foundation

Copenhagen Hospital Corporation

Rigshospitalet, Denmark

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Atherosclerosis

Polycystic Ovary Syndrome

Cysts

Ovarian Cysts

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Gonadal Disorders

Endocrine System Diseases

All Drugs and Chemicals

Androgens

David Siscovick

To examine whether serum androgens, measured earlier in life, and variation in genes related to androgen synthesis, metabolism, and signaling are associated with early-onset subclinical coronary atherosclerosis in young adult women from the community.

BACKGROUND:

Polycystic ovary syndrome (PCOS) is denoted by hyperandrogenism and symptoms of ovulation dysfunction (e.g., infertility, oligomenorrhea). Women who are diagnosed with PCOS represent the more extreme end of abnormal ovarian function. While PCOS is rare, approximately 20 percent of women are expected to have subclinical polycystic ovaries, identified by sonogram. Factors that are associated with PCOS, insulin resistance and dyslipidemia, are also risk factors for coronary artery disease and there is evidence to suggest that women with PCOS are more likely to experience coronary artery disease. This raises the question: are subclinical cases of polycystic ovaries at increased risk of coronary artery disease?

The study is ancillary to the the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a large cohort study supported by the NHLBI. The CARDIA population provides a unique opportunity to explore these associations because there is a 15-year period of risk factor ascertainment in this population including stored blood + DNA specimens from which serum androgens and relevant genetic markers can be ascertained. In addition, all participants will have coronary artery calcium (CAC) determinations at the year 15 exam. In the ancillary study an additional year 16 visit will occur for the purpose of obtaining a trans vaginal ultrasound determination (TVUS) so as to obtain clinical evidence of hyperandrogenism and look at the joint effects of the clinical evidence and serum markers as predictors of CAC. The study is in response to an initiative on Ancillary Studies in Heart, Lung, and Blood Disease Trials released in June, 2000.

DESIGN NARRATIVE:

The ancillary study in year 16 of CARDIA will recall 1,200 women who received a coronary artery calcification (CAC) determination in year 15. These women will have an additional blood draw three to 10 days after their last menstrual period, will have a questionnaire administered to them regarding clinical symptoms of PCOS (polycystic ovarian syndrome) and other aspects of hyperandrogenism. Two principal analyses will be performed. The first is a longitudinal analysis using year 2 and year 10 data to use serum markers of hyperandrogenism and genetic markers from DNA samples as predictors of CAC which is defined as present (absent) and is determined at the year 15 examination. The principal method of analysis will be logistic regression. An additional analysis will relate androgen levels at year 2 to lipid levels and other coronary risk factors ascertained at year 2, 7, 10 and 15.

Androgens and Subclinical Atherosclerosis in Young Women - Ancillary to CARDIA

National Heart, Lung, and Blood Institute (NHLBI)

University of Washington

Nutritional and Metabolic Diseases

Nervous System Diseases

Behaviors and Mental Disorders

Respiratory Tract (Lung and Bronchial) Diseases

Digestive System Diseases

Infections

Immune System Diseases

Rare Diseases

Diabetes Mellitus

Dementia

Death

Pulmonary Disease, Chronic Obstructive

Respiratory Insufficiency

Kidney Failure, Chronic

Renal Insufficiency

Heart Failure

Stroke

Liver Failure

Hepatic Insufficiency

Lung Diseases

Acquired Immunodeficiency Syndrome

HIV Infections

Immunologic Deficiency Syndromes

Pneumonia

Failure to Thrive

Communicable Diseases

Respiratory Tract Diseases

Brain Diseases

Central Nervous System Diseases

Respiration Disorders

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Chronic Disease

Disease Attributes

Lung Diseases, Obstructive

Blood-Borne Infections

Sexually Transmitted Diseases

Sexually Transmitted Diseases, Viral

Lentivirus Infections

Retroviridae Infections

Virus Diseases

RNA Virus Infections

Slow Virus Diseases

Liver Diseases

Gastrointestinal Diseases

Cerebrovascular Disorders

Renal Insufficiency, Chronic

Chronic Graft Versus Host Disease

Multidisciplinary palliative care team met with patient

Ingrid M Venohr, RN, PhD

Douglas A Conner, PhD

Marcia Liberson, MSW,MPH

Palliative care is believed to improve care of patients with life-limiting illnesses. This study evaluated the impact of a multi-center randomized trial of a palliative care team intervention on the quality and cost of care of hospitalized patients. Study subjects were randomized to intervention or usual care. At study end, patients receiving the palliative care intervention reported greater patient satisfaction with their care. Intervention patients also had significantly fewer ICU admissions and lower total costs for care 6 months past their hospitalization. Intervention patients completed more advance directives and had longer hospice stays.

The Inpatient Palliative Care Service (IPCS) was implemented at three Kaiser-Permanente sites: Colorado, Portland and San Francisco. The service consisted of a physician, nurse, social worker, and spiritual counselor who worked with the study subjects randomized to receive the intervention. The intervention included symptom control, emotional and spiritual support, advance care and post-discharge care planning, There were no differences in symptom control or emotional support but IPCS patient reported better spiritual support compared to usual care patients. IPCS patients also reported greater satisfaction with their hospital care experience and better communication with their providers. Both IPCS and usual care patients reported improved quality of life during their enrollment hospital stay. IPCS patients completed more advance directives. IPCS patients had more home health visits than usual care patients but significantly fewer ICU admissions. IPCS patients had significantly lower hospital costs and higher pharmacy costs, than the usual care patients. IPCS patients had significantly lower (p= .001) total health services costs (a cost savings of $64.90 per patient per day) compared to usual care patients. This translated to an average total cost savings of $3,185 per enrolled patient. IPCS patients had a significantly longer average hospice length of stay. There were no differences between IPC and usual care patients in the proportion admitted to hospice, time to hospice admission, the average length of survival, or proportion of those who survived to 6 months.

Conclusion: IPCS resulted in better spiritual support, a better hospital care experience, better communication with their providers, increased completion of advance directives, fewer ICU admissions, longer hospice stays and reduced overall health care costs.

Multidisciplinary Inpatient Palliative Care Intervention

A Multi-Site Replication of an Inpatient Palliative Care Program

Garfield Memorial Fund

Kaiser Permanente

Skin and Connective Tissue Diseases

Blood and Lymph Conditions

Substance Related Disorders

Wounds and Injuries

Lung Neoplasms

Carcinoma

Breast Neoplasms

Lymphoma

Cardiotoxicity

Carcinoma, Intraductal, Noninfiltrating

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

Radiation Injuries

Adenocarcinoma

Carcinoma in Situ

Breast Carcinoma In Situ

Lymphosarcoma

Bone Density Conservation Agents

Calcium

Calcium, Dietary

Patients who had received radiotherapy will be sub-stratified into those who received treatment to the left or right breast.

Patients who did not receive radiation treatment, but received chemotherapy, hormonal therapy, and/or surgery will be used as study controls to compare the prevalence and burden of cardiac disease as compared to radiation patients.

Lucille Lee, MD

Lindsay L Puckett, MD

CAROLE seeks to evaluate the relationship between chest Radiation Therapy and coronary artery disease.

The purpose of CAROLE is to check the heart health of women who received breast cancer treatments in the past and protect them from future heart disease.

Background: Within the United States, there are an estimated 3.1 million women alive who have been diagnosed with invasive breast cancer, and approximately 56% of them have received radiation. Worldwide, there are 1.4 million diagnosed annually and, in 2012, it was the most commonly diagnosed cancer in women. As patients continue to live longer, cardiac dose-related toxicity has become an issue which impacts millions globally. Guidelines are sorely needed for this large at-risk population of women.

Purpose: Radiation therapy to the chest has known cardiac late effects including coronary artery disease, fibrosis, and valvular dysfunction. Unfortunately, there is no clear evidence on which radiation doses to cardiac structures cause these late toxicities. As a result, these effects are often under-recognized until after patients have become symptomatic. More than half of breast cancer patients are treated with radiation, and many receive incidental cardiac irradiation. Many of these women also receive systemic therapy which may pose additional cardiac risks. The investigators data will help to establish baseline rates of pre-clinical and clinical disease, which can be used to inform preventative guidelines that are critically needed in this at-risk population. Additionally, the investigators data will provide a better definition of the radiation dose-relationship associated with cardiac toxicity so that it will be possible to predict more accurately who is at elevated risk for iatrogenic cardiac disease.

Research Plan: This study will identify and evaluate 200 breast cancer patients treated at the investigators institution (\>6 years prior) who are at risk for treatment-related cardiac toxicity. All patients enrolled in the study will receive echocardiograms (echo), electrocardiograms (EKGs), and coronary calcium (CAC) CT scans in order to comprehensively evaluate for pre-clinical and clinical cardiac disease. Patients identified as having cardiac disease during testing will be offered referral to a cardiologist. Patients who received non-radiation treatments (chemotherapy, hormonal therapy, and/or surgery) will be compared to radiated patients to establish baseline rates of preclinical and clinical disease. Patients who received cardiotoxic systemic therapy (doxorubicin, trastuzumab, etc.) will also be evaluated in subgroup analysis. Among radiation patients, this study proposes a novel method of risk assessment, which is, to utilize a patient's stored treatment plan (from 2004-2011) and fuse it with patients current cardiac imaging to delineate an accurate dose relationship associated with clinical and pre-clinical disease. This is further described in the specific aims below:

Specific Aim 1: Identify baseline levels of clinical and pre-clinical disease in breast cancer patients.

Aim 1.1: Delineate the group of patients diagnosed and treated for breast cancer between 2004-2011, enroll health system patients with recent follow up (within 3 years).

Aim 1.2: Perform non-invasive cardiac testing (EKG, echo, CAC CT scans). Aim 1.3: Establish rates of pre-clinical and clinical disease based on pre-determined criteria.

Specific Aim 2: Create an accurate dosimetric assessment of dose to cardiac structures.

Aim 1.1: Among study patients who received radiation treatment for breast cancer, obtain stored planning CT simulation scans.

Aim 1.2: Upload CT simulation scans with dosimetric information and delineate cardiac structures at risk in order to ensure accurate and reproducible target delineation.

Aim 1.3: Fuse the CAC CT scan with the CT simulation scan to accurately assess for dose correlation between coronary calcium with the dose received.

Aim 1.4: Create a dose-relationship model for the heart and cardiac structures.

Specific Aim 3: Incorporate dosimetric cardiac risk information into the investigators institution's clinical practice, publish data, and establish updated cardiac guidelines for women who have received radiation for breast cancer.

The long-term goal of the project is to elucidate specific treatment and radiation dose-related risks, which will then be used to inform follow-up recommendations and guidelines. This project will impact the way investigators describe expected cardiac risk to patients, the way the investigators recommend follow up care, and potentially, the way the investigators prescribe treatment. At present, all patients receiving radiation for breast cancer are informed that there is a risk of cardiac late effects, however, no specific cardiac imaging or intervention is recommended other than routine medical follow up. There is little distinction given to the side of the cancer, a patient's individual anatomy, or the projected dose to the anterior heart and cardiac structures. This project will allow physicians to provide a more accurate risk profile regarding future risk of cardiac morbidity. If the study reveals a very high rate of pre-clinical atherosclerotic disease, it also may prompt more routine CAC CT screening.

The CAROLE (CArdiac Related Oncologic Late Effects) Study

Sub-analysis for association of specific oncologic treatment(s) with cardiac disease (as per previously described study templates) will also be performed on patients who received multimodality treatment (RT+ chemotherapy, RT + hormonal treatment, RT+ chemo and hormonal treatment, RT + individual cardio toxic chemotherapies \[anthracycline, trastuzumab, etc.\]) and on different surgical approaches (lumpectomy and mastectomy). Results will be reported as a single value for each arm/group.

Assess whether radiation to the heart is associated with increased pre-clinical and clinical cardiac disease (as determined by a composite of multimodality cardiology assessments including EKG.

Studies will be read using a standard, evidence based, set of criterion and documented using study templates) and compared to patients who did not receive radiation to the heart.

All cardiac tests will be reviewed and reported as a composite with one the following; No evidence of disease/unrelated, preclinical disease, or clinical disease (non-numerically) based on the Cardiologists read of the study based on standard Pre-Specified criteria.

Assess whether radiation to the heart is associated with increased pre-clinical and clinical cardiac disease (as determined by a composite of multimodality cardiology assessments including Echocardiogram with Strain.

All cardiac tests will be reviewed and reported as a composite with one the following; No evidence of disease/unrelated, preclinical disease, or clinical disease (non-numerically) based on the Cardiologists read of the study based on standard Pre-Specified criteria.

Assess whether radiation to the heart is associated with increased pre-clinical and clinical cardiac disease (as determined by a composite of multimodality cardiology assessments including Coronary Artery Calcium (CAC) CT.

All cardiac tests will be reviewed and reported as a composite with one the following; No evidence of disease/unrelated, preclinical disease, or clinical disease (non-numerically) based on the Cardiologists read of the study based on standard Pre-Specified criteria.

Individual cardiac structures will be accessed using Agatston score. Agatston score is calculated using a CAC CT scan to measure for the presence of coronary artery disease based on the extent of coronary artery calcification. Specifically the left main, left anterior descending, left circumflex, and right coronary arteries are all read individually and the sum of these cardiac vessels scores is read as the overall Agatston score.

Grading of coronary artery disease (based on total calcium score) measure is without units. Score categories are as follows: No evidence of disease/unrelated, preclinical disease, or clinical disease (non-numerically). Higher Agatston score correlates with more coronary artery disease.

The assessment of calcium (Agatston score) on CAC CT will be compared to the dose received by the specified vessel as determined using deformable registration with prior radiation imaging (simulation CT scan).

Northwell Health

Principal Investigator

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Cleansing of Suction Blood in Cardiac Surgery for Reduced Inflammatory Response	NCT00159926	Systemic Inflam... Coronary Arteri...	Cell saver No cell saver	18 Years -	Rigshospitalet, Denmark
Androgens and Subclinical Atherosclerosis in Young Women - Ancillary to CARDIA	NCT00037245	Cardiovascular ... Coronary Arteri... Heart Diseases Polycystic Ovar...		- 100 Years	University of Washington
Multidisciplinary Inpatient Palliative Care Intervention	NCT00325611	Cerebrovascular... Cancer Coronary Arteri... Heart Failure, ... Diabetes Mellit... Acquired Immuno... Failure to Thri... Pulmonary Disea... Dementia Kidney Failure,... Pneumonia Liver Failure Renal Failure Respiratory Fai... Stroke	Multidisciplina...	18 Years -	Kaiser Permanente
The CAROLE (CArdiac Related Oncologic Late Effects) Study	NCT03235427	Coronary Artery... Cardiac Disease Cardiac Toxicit... Radiation Radiation Thera... Atherosclerotic... Cardiotoxicity Breast Cancer Lung Cancer Lymphoma Cancer Carcinoma, Intr...		26 Years - 78 Years	Northwell Health
Cleansing of Suction Blood in Cardiac Surgery for Reduced Inflammatory Response	NCT00159926	Systemic Inflam... Coronary Arteri...	Cell saver No cell saver	18 Years -	Rigshospitalet, Denmark

Spots Global Cancer Trial Database for coronary arteriosclerosis