Ana Barac

Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.

Cardiac dysfunction resulting from exposure to cancer therapeutics was first recognized in the 1960s, with the widespread introduction of anthracyclines into the oncologic therapeutic armamentarium. Heart failure (HF) associated with anthracyclines was then recognized as an important side effect. As a result, physicians learned to limit their doses to avoid cardiac dysfunction. Several strategies have been used over the past decades to detect it. Two of them evolved over time to be very useful: endomyocardial biopsies and monitoring of left ven- tricular (LV) ejection fraction (LVEF) by cardiac imaging. Examination of endomyocardial biopsies proved to be the most sensitive and spe- cific parameter for the identification of anthracycline-induced LV dysfunction and became the gold standard in the 1970s. However, the interest in endomyocardial biopsy has diminished over time because of the reduction in the cumulative dosages used to treat ma- lignancies, the invasive nature of the procedure, and the remarkable progress made in noninvasive cardiac imaging. The noninvasive evaluation of LVEF has gained importance, and notwithstanding the limitations of the techniques used for its calculation, has emerged as the most widely used strategy for monitoring the changes in cardiac function, both during and after the administration of potentially car- diotoxic cancer treatment.

Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging

### A. Definition, classification, and mechanisms of toxicity Cardiac dysfunction resulting from exposure to cancer therapeutics was first recognized in the 1960s, with the widespread introduction of anthracyclines into the oncological therapeutic armamentarium.1 Heart failure (HF) associated with anthracyclines was then recognized as an important side effect. As a result, physicians learned to limit their doses to avoid cardiac dysfunction.2 Several strategies have been used over the past decades to detect it. Two of them evolved over time to be very useful: endomyocardial biopsies and monitoring of left ventricular (LV) ejection fraction (LVEF) by cardiac imaging. Examination of endomyocardial biopsies proved to be the most sensitive and specific parameter for the identification of anthracycline-induced LV dysfunction and became the gold standard in the 1970s. However, the interest in endomyocardial biopsy has diminished over time because of the reduction in the cumulative dosages used to treat malignancies, the invasive nature of the procedure, and the remarkable progress made in non-invasive cardiac imaging. The non-invasive evaluation of LVEF has gained importance, and notwithstanding the limitations of the techniques used for its calculation, has emerged as the most widely used strategy for monitoring the changes in cardiac function, both during and after the administration of potentially cardiotoxic cancer treatment.3–5 The timing of LV dysfunction can vary among agents. In the case of anthracyclines, the damage occurs immediately after the exposure;6 for others, the time frame between drug administration and detectable cardiac dysfunction appears to be more variable. Nevertheless, the heart has significant cardiac reserve, and the expression of damage in the form of alterations in systolic or diastolic parameters may not be overt until a substantial amount of cardiac reserve has been exhausted. Thus, cardiac damage may not become apparent until years or even decades after receiving the cardiotoxic treatment. This is particularly applicable to …

2012 American College of Cardiology Foundation/Society for Cardiovascular Angiography and Interventions Expert Consensus Document on Cardiac Catheterization Laboratory Standards update: A report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents

published online May 8, 2012; J. Am. Coll. Cardiol. L. Tommaso Carl Moliterno, John W.M. Moore, Sandra M. Oliver-McNeil, Jeffrey J. Popma, and Landzberg, Warren K. Laskey, Charles R. McKay, Julie M. Miller, David J. Cavendish, Charles E. Chambers, James Bernard Hermiller, Jr, Scott Kinlay, Joel S. M. Bashore, MD, FACC,, Stephen Balter, Ana Barac, John G. Byrne, Jeffrey J. Documents, Society of Thoracic Surgeons, Society for Vascular Medicine, Thomas American College of Cardiology Foundation Task Force on Expert Consensus Catheterization Laboratory Standards Update Angiography and Interventions Expert Consensus Document on Cardiac 2012 American College of Cardiology Foundation/Society for Cardiovascular This information is current as of May 25, 2012 http://content.onlinejacc.org/cgi/content/full/j.jacc.2012.02.010v1 located on the World Wide Web at: The online version of this article, along with updated information and services, is

Methods for Evaluating Endothelial Function in Humans

The endothelium is the main regulator of vascular wall homeostasis. Physiologically, endothelial cells maintain a relaxed vascular tone and low levels of oxidative stress, in part by releasing mediators, including NO, prostacyclin (PGI2), and endothelin (ET-1), and controlling local angiotensin II activity.1 In addition, the endothelium actively regulates vascular permeability to plasma constituents, platelet and leukocyte adhesion and aggregation, and thrombosis.1 This state of balanced endothelial regulation of blood vessel function is, however, altered by a number of conditions. Thus, in response to a variety of noxious stimuli, the endothelium undergoes a phenotypic modulation to a nonadaptive state, commonly termed “endothelial dysfunction,” characterized by loss or dysregulation of homeostatic mechanisms operative in healthy endothelial cells. This pathophysiological condition is associated with increased expression of adhesion molecules, increased synthesis of proinflammatory and prothrombotic factors, increased oxidative stress, and abnormal modulation of vascular tone, which may lead to different functional manifestations, including impaired endothelium-dependent vasodilation.2 Current evidence suggests that endothelial dysfunction occurs early in the process of atherogenesis and contributes to the formation, progression, and complications of the atherosclerotic plaque.3 Several studies from our and other laboratories have shown that patients with cardiovascular risk factors but no clinical evidence of atherosclerosis have endothelial dysfunction, indicated by an impaired response to endothelial vasodilator agents, such as acetylcholine and bradykinin.4 Combined with the pathophysiological role of the endothelium described above, these observations strongly suggest that endothelial dysfunction is a common mechanistic link between risk factors and the development of atherosclerosis. Furthermore, recent reports have demonstrated that endothelial dysfunction is an independent predictor of future cardiovascular events in patients with atherosclerotic risk factors,5,6 in patients with stable ischemic heart disease,7 and in patients with acute coronary syndromes.8 Thus, endothelial dysfunction appears to be a systemic vascular …

Prevention and Monitoring of Cardiac Dysfunction in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline

Purpose Cardiac dysfunction is a serious adverse effect of certain cancer-directed therapies that can interfere with the efficacy of treatment, decrease quality of life, or impact the actual survival of the patient with cancer. The purpose of this effort was to develop recommendations for prevention and monitoring of cardiac dysfunction in survivors of adult-onset cancers. Methods Recommendations were developed by an expert panel with multidisciplinary representation using a systematic review (1996 to 2016) of meta-analyses, randomized clinical trials, observational studies, and clinical experience. Study quality was assessed using established methods, per study design. The guideline recommendations were crafted in part using the Guidelines Into Decision Support methodology. Results A total of 104 studies met eligibility criteria and compose the evidentiary basis for the recommendations. The strength of the recommendations in these guidelines is based on the quality, amount, and consistency of the evidence and the balance between benefits and harms. Recommendations It is important for health care providers to initiate the discussion regarding the potential for cardiac dysfunction in individuals in whom the risk is sufficiently high before beginning therapy. Certain higher risk populations of survivors of cancer may benefit from prevention and screening strategies implemented during cancer-directed therapies. Clinical suspicion for cardiac disease should be high and threshold for cardiac evaluation should be low in any survivor who has received potentially cardiotoxic therapy. For certain higher risk survivors of cancer, routine surveillance with cardiac imaging may be warranted after completion of cancer-directed therapy, so that appropriate interventions can be initiated to halt or even reverse the progression of cardiac dysfunction.

2012 American College of Cardiology Foundation/Society for Cardiovascular Angiography and Interventions expert consensus document on cardiac catheterization laboratory standards update: A report of the American College of Cardiology Foundation Task Force on Expert Consensus documents developed in collaboration with the Society of Thoracic Surgeons and Society for Vascular Medicine.

published online May 8, 2012; J. Am. Coll. Cardiol. L. Tommaso Carl Moliterno, John W.M. Moore, Sandra M. Oliver-McNeil, Jeffrey J. Popma, and Landzberg, Warren K. Laskey, Charles R. McKay, Julie M. Miller, David J. Cavendish, Charles E. Chambers, James Bernard Hermiller, Jr, Scott Kinlay, Joel S. M. Bashore, MD, FACC,, Stephen Balter, Ana Barac, John G. Byrne, Jeffrey J. Documents, Society of Thoracic Surgeons, Society for Vascular Medicine, Thomas American College of Cardiology Foundation Task Force on Expert Consensus Catheterization Laboratory Standards Update Angiography and Interventions Expert Consensus Document on Cardiac 2012 American College of Cardiology Foundation/Society for Cardiovascular This information is current as of May 25, 2012 http://content.onlinejacc.org/cgi/content/full/j.jacc.2012.02.010v1 located on the World Wide Web at: The online version of this article, along with updated information and services, is

Cardiovascular Health of Patients With Cancer and Cancer Survivors : A Roadmap to the Next Level

Many existing and emerging cancer therapies have a significant effect on the cardiovascular health of patients with cancer and cancer survivors. This paper examines current aspects of interdisciplinary cardio-oncology clinical care delivery and education in the United States and outlines how these data provide a platform for future development of the field. We present the results of the nationwide survey on cardio-oncology services, practices, and opinions, conducted among chiefs of cardiology and program directors, which demonstrate ranges of clinical activities and identify significant interest for increased educational opportunities and expert training of cardiovascular physicians in this field. The survey respondents recognized clinical relevance but emphasized lack of national guidelines, lack of funds, and limited awareness and infrastructure as the main challenges for development and growth of cardio-oncology. We discuss potential solutions to unmet needs through interdisciplinary collaboration and the active roles of professional societies and other stakeholders.

Burgeoning Cardio-Oncology Programs: Challenges and Opportunities for Early Career Cardiologists/Faculty Directors

From 1935 to 2013, cardiovascular diseases and cancer have been the 2 leading causes of death such that, in 2010, heart disease and cancer accounted for 46% of all deaths in the United States [(1)][1]. Notwithstanding, owing to the success gained in finding treatments and cures for various cancers,

2012 American College of Cardiology Foundation/ Society for Cardiovascular Angiography and Interventions Expert Consensus Document on Cardiac Catheterization Laboratory Standards Update

published online May 8, 2012; J. Am. Coll. Cardiol. L. Tommaso Carl Moliterno, John W.M. Moore, Sandra M. Oliver-McNeil, Jeffrey J. Popma, and Landzberg, Warren K. Laskey, Charles R. McKay, Julie M. Miller, David J. Cavendish, Charles E. Chambers, James Bernard Hermiller, Jr, Scott Kinlay, Joel S. M. Bashore, MD, FACC,, Stephen Balter, Ana Barac, John G. Byrne, Jeffrey J. Documents, Society of Thoracic Surgeons, Society for Vascular Medicine, Thomas American College of Cardiology Foundation Task Force on Expert Consensus Catheterization Laboratory Standards Update Angiography and Interventions Expert Consensus Document on Cardiac 2012 American College of Cardiology Foundation/Society for Cardiovascular This information is current as of May 25, 2012 http://content.onlinejacc.org/cgi/content/full/j.jacc.2012.02.010v1 located on the World Wide Web at: The online version of this article, along with updated information and services, is

Does cardiovascular phenotype explain the association between diabetes and incident heart failure? The Strong Heart Study.

BACKGROUND AND AIMS Diabetes remains a predictor of incident heart failure (HF), independent of intercurrent myocardial infarction (MI) and concomitant risk factors. Initial cardiovascular (CV) characteristics, associated with incident heart failure (HF) might explain the association of diabetes with incident HF. METHODS AND RESULTS Participants to the 2nd Strong Heart Study exam, without prevalent HF or coronary heart disease, or glomerular filtration rate <30 mL/min/1.73 m(2), were analyzed (n = 2757, 1777 women, 1278 diabetic). Cox regression of incident HF (follow-up 8.91 ± 2.76 years) included incident MI censored as a competing risk event. Acute MI occurred in 96 diabetic (7%) and 84 non-diabetic participants (6%, p = ns). HF occurred in 156 diabetic (12%) and in 68 non-diabetic participants (5%; OR = 2.89, p < 0.001). After accounting for competing MI and controlling for age, gender, BMI, systolic blood pressure, smoking habit, plasma cholesterol, antihypertensive treatment, heart rate, fibrinogen and C-reactive protein, incident HF was predicted by greater LV mass index, larger left atrium, lower systolic function, greater left atrial systolic force and urinary albumin/creatinine excretion. Risk of HF was reduced with more rapid LV relaxation and anti-hypertensive therapy. Diabetes increases hazard of HF by 66% (0.02 < p < 0.001). The effect of diabetes could be explained by the level of HbA1c. CONCLUSIONS Incident HF occurs more frequently in diabetes, independent of intercurrent MI, abnormal LV geometry, subclinical systolic dysfunction and indicators of less rapid LV relaxation, and is influenced by poor metabolic control. Identification of CV phenotype at high-risk for HF in diabetes should be advised.