The Role of Cardiovascular Magnetic Resonance for Surveillance of Cardiac Performance upon Receipt of Potentially Cardiotoxic Cancer Therapeutics

Purpose of Review

Advancements in cancer treatment have resulted in improved cancer-related survival and consequently an increase in the number of cancer survivors. Unfortunately, associated with this increase in cancer-related survivorship, cardiac events have occurred with increasing frequency in cancer survivors. Recognition that cancer survivors are at increased risk for cardiovascular (CV) morbidity has generated interest to develop cardiac imaging techniques that identify subclinical CV disease during receipt of potentially cardiotoxic cancer treatment. Since subclinical cardiovascular disease precedes future cardiac events, early recognition of subclinical CV disease during receipt of potentially cardiotoxic cancer treatment offers the opportunity to initiate strategies that prevent further evolution of subclinical CV disease as well as cardiac events.

Recent Findings

Cardiovascular magnetic resonance imaging (CMR) is an advanced imaging technique that identifies imaging markers of subclinical cardiovascular disease in patients receiving potentially cardiotoxic cancer treatment regimens. In this article, we review the use of CMR for identifying subclinical cardiac disease in patients receiving potentially cardiotoxic cancer treatment regimens.

Summary

The ability of contemporary CMR to accurately define cardiac anatomy, function, and tissue characteristics may represent a critical tool to assess patients with cancer.

     

Myocardial Extracellular Volume Quantification by Cardiovascular Magnetic Resonance and Computed Tomography

Purpose of review

This review article discusses the evolution of extracellular volume (ECV) quantification using both cardiovascular magnetic resonance (CMR) and computed tomography (CT).

Recent findings

Visualizing diffuse myocardial fibrosis is challenging and until recently, was restricted to the domain of the pathologist. CMR and CT both use extravascular, extracellular contrast agents, permitting ECV measurement. The evidence base around ECV quantification by CMR is growing rapidly and just starting in CT. In conditions with high ECV (amyloid, oedema and fibrosis), this technique is already being used clinically and as a surrogate endpoint. Non-invasive diffuse fibrosis quantification is also generating new biological insights into key cardiac diseases.

Summary

CMR and CT can estimate ECV and in turn diffuse myocardial fibrosis, obviating the need for invasive endomyocardial biopsy. CT is an attractive alternative to CMR particularly in those individuals with contraindications to the latter. Further studies are needed, particularly in CT.

     

Receipt of Cancer Screening Is a Predictor of Life Expectancy

Background

Obtaining cancer screening on patients with limited life expectancy has been proposed as a measure for low quality care for primary care physicians (PCPs). However, administrative data may underestimate life expectancy in patients who undergo screening.

Objective

To determine the association between receipt of screening mammography or PSA and overall survival.

Design

Retrospective cohort study from 1/1/1999 to 12/31/2012. Receipt of screening was assessed for 2001–2002 and survival from 1/1/2003 to 12/31/2012. Life expectancy was estimated as of 1/1/03 using a validated algorithm, and was compared to actual survival for men and women, stratified by receipt of cancer screening.

Participants

A 5 % sample of Medicare beneficiaries aged 69–90 years as of 1/1/2003 (n?=?906,723).

Interventions

Receipt of screening mammography in 2001–2002 for women, or a screening PSA test in 2002 for men.

Main Measures

Survival from 1/1/2003 through 12/31/2012.

Key Results

Subjects were stratified by life expectancy based on age and comorbidity. Within each stratum, the subjects with prior cancer screening had actual median survivals higher than those who were not screened, with differences ranging from 1.7 to 2.1 years for women and 0.9 to 1.1 years for men. In a Cox model, non-receipt of screening in women had an impact on survival (HR?=?1.52; 95 % CI?=?1.51, 1.54) similar in magnitude to a diagnosis of complicated diabetes or heart failure, and was comparable to uncomplicated diabetes or liver disease in men (HR?=?1.23; 1.22, 1.25).

Conclusions

Receipt of cancer screening is a powerful marker of health status that is not captured by comorbidity measures in administrative data. Because life expectancy algorithms using administrative data underestimate the life expectancy of patients who undergo screening, they can overestimate the problem of cancer screening in patients with limited life expectancy.

     

Complications of acromegaly: thyroid and colon

Introduction

In acromegaly the long-term exposure to high growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels may result in specific complications in different human organs, including the thyroid gland and the colon.

Materials and Methods

We will review here the evidence available regarding the characteristic thyroid and colon complications in acromegaly.

Results

This review summarizes the published data observing noncancerous structural abnormalities (thyroid nodules, colonic polyps) and thyroid and colon cancer in patients diagnosed with acromegaly.

Conclusion

Thyroid micro-carcinomas are probably over-diagnosed among acromegalic patients. In regard to colon cancer, there is no sufficient data to suggest that colon cancer risk is higher in acromegaly compared to the general population.

     

Establishing a General Medical Outpatient Clinic for Cancer Survivors in a Public City Hospital Setting

INTRODUCTION

Many cancer centers and community hospitals are developing novel models of survivorship care. However, few are specifically focused on services for socio-economically disadvantaged cancer survivors.

AIMS

To describe a new model of survivorship care serving culturally diverse, urban adult cancer patients and to present findings from a feasibility evaluation.

SETTING

Adult cancer patients treated at a public city hospital cancer center.

PROGRAM DESCRIPTION

The clinic provides comprehensive medical and psychosocial services for patients within a public hospital cancer center where they receive their oncology care.

PROGRAM EVALUATION

Longitudinal data collected over a 3-year period were used to describe patient demographics, patient needs, and services delivered. Since inception, 410 cancer patients have been served. Demand for services has grown steadily. Hypertension was the most frequent comorbid condition treated. Pain, depression, cardiovascular disease, hyperlipidemia, and bowel dysfunction were the most common post-treatment problems experienced by the patients. Financial counseling was an important patient resource.

DISCUSSION

This new clinical service has been well-integrated into its public urban hospital setting and constitutes an innovative model of health-care delivery for socio-economically challenged, culturally diverse adult cancer survivors.

     

Role of Cardiac Magnetic Resonance Imaging in Valvular Heart Disease: Diagnosis,Assessment, and Management

Purpose of Review

This article will review the current techniques in cardiac magnetic resonance imaging (CMR) for diagnosing and assessing primary valvular heart disease.

Recent Findings

The recent advancements in CMR have led to an increased role of this modality for qualifying and quantifying various native valve diseases. Phase-contrast velocity encoded imaging is a well-established technique that can be used to quantify aortic and pulmonic flow. This technique, combined with the improved ability for CMR to obtain accurate left and right ventricular volumetrics, has allowed for increased accuracy and reproducibility in assessing valvular dysfunction. Advancements in CMR technology also allows for improved spatial and temporal resolution imaging of various valves and their regurgitant or stenotic jets. Therefore, CMR can be a powerful tool in evaluation of native valvular heart disease.

Summary

The role of CMR in assessing valvular heart disease is growing and being recognized in recent guidelines. CMR has the ability to assess valve morphology along with qualifying and quantifying valvular disease. In addition, the ability to obtain accurate volumetric measurements may improve more precise management strategies and may lead to improvements in mortality and morbidity.

     

Update on Incorporating Biomarkers with Imaging Findings for the Detection and Management of Cardiotoxicity

Purpose of Review

Modern cancer therapy comes at a cost of increased risk of cardiotoxicity. The purpose of our paper is to provide an updated review highlighting research incorporating biomarkers and imaging findings for the detection of subclinical cardiac dysfunction and management of cancer treatment-related cardiotoxicity.

Recent Findings

Biomarkers, particularly troponin, NTproBNP, and myeloperoxidase, have been shown to have a predictive role in the development of cancer treatment-related cardiotoxicity. Early reductions in global longitudinal strain and the more recently reported, circumferential strain, have been shown to be predictive of subsequent cardiotoxicity. Integrating troponin levels with longitudinal strain may have incremental value in predicting future cardiotoxicity. Initiating troponin-guided heart failure therapy following cancer treatment may impact the development of cardiotoxicity. Strain-guided heart failure therapy is currently under investigation.

Summary

Early detection of subclinical cardiac dysfunction in high-risk cancer patients and subsequent medical intervention using biomarkers and imaging may help to alter the course of cancer treatment-induced cardiotoxicity. Current guidelines and expert consensus offer a general framework for monitoring high risk patients for cardiotoxicity. However, additional research is needed to provide a more sophisticated and structured approach in detecting and managing subclinical cardiac dysfunction with hopes of minimizing subsequent cardiotoxicity.

     

The Emerging Role of Cardiac Magnetic Resonance Imaging in the Evaluation of Patients with HFpEF

Purpose of Review

To give an update on the emerging role of cardiac magnetic resonance imaging in the evaluation of patients with heart failure with preserved ejection fraction (HFpEF). This is important as the diagnosis of HFpEF remains challenging and cardiac imaging is pivotal in establishing the function of the heart and whether there is evidence of structural heart disease or diastolic dysfunction. Echocardiography is widely available, although the gold standard in quantifying heart function is cardiac magnetic resonance (CMR) imaging.

Recent Findings

This review includes the recently updated 2016 European Society of Cardiology guidelines on diagnosing HFpEF that define the central role of imaging in identifying patients with HFpEF. Moreover, it includes the pathophysiology in HFpEF, how CMR works, and details current CMR techniques used to assess structural heart disease and diastolic function. Furthermore, it highlights promising research techniques that over the next few years may become more used in identifying these patients.

Summary

CMR has an emerging role in establishing the diagnosis of HFpEF by measuring the left ventricular ejection fraction (LVEF) and evidence of structural heart disease and diastolic dysfunction.

     

Pros and Cons of Intensive Systolic Blood Pressure Lowering

Purpose of Review

The Systolic Blood Pressure Intervention Trial demonstrated significant decreases in cardiovascular events and total mortality with intensive systolic blood pressure lowering in adults with high cardiovascular risk in the absence of diabetes but benefits were accompanied by increased risk of adverse events.

Recent Findings

Over 100,000 deaths and 46,000 cases of heart failure may be prevented annually if intensive systolic blood pressure lowering is implemented in 17 million US adults who are age 50 years and older, and have high cardiovascular risk in the absence of diabetes and meet eligibility for the Systolic Blood Pressure Intervention Trial. However, the benefits of intensive SBP lowering will be accompanied by an excess of 43,000 cases of electrolyte abnormalities and 88,000 cases of acute kidney injury.

Summary

Physicians should consider implementation of intensive systolic blood pressure lowering in appropriate patients who understand the risks and benefits of this intervention.

     

Updates on the Role of Imaging in Cardiac Sarcoidosis

Purpose of review

The non-specific symptom profile and subclinical nature of disease along with variable region of cardiac involvement in systemic sarcoidosis make the diagnosis particularly challenging. The yield of endomyocardial biopsy, a gold standard for diagnosis, is not high unless coupled with additional imaging modalities to detect regional involvement. This review is focused on highlighting the major recent advances in imaging modalities and diagnosis of cardiac sarcoidosis.

Recent findings

There has been much interest and increasing research focused on developing newer and improved imaging modalities to establish diagnosis. CMR and ¹⁸F- FDG-PET are now considered imaging modalities of choice in most centers worldwide, but the data comparing both methodologies head-to-head is limited. Nevertheless, novel radiotracers (i.e. ⁶⁸Ga-DOTANOC, ¹⁸F-Flurpiridaz, ¹³N-Ammonia) and hybrid combination PET/CMR imaging are coming to spotlight with improved sensitivity and specificity for earlier detection of myocardial sarcoid.

Summary

As CMR and PET are showing increased utilization in cardiac sarcoidosis, ²⁰¹Th-SPECT, ^99mTc MDP SPECT, ⁶⁷Ga Scintigraphy, and ⁸²Rb PET are falling out of favor. Newer imaging modalities, radionuclide tracers, and hybrid PET/CMR combinations have been promising in better detecting cardiac sarcoidosis and are currently being evaluated in larger trials.

     

Pregnancy Among Survivors of Childhood Cancer: Cardiovascular Considerations

Purpose of review

To educate clinicians on cardiovascular considerations and management strategies surrounding pregnancy in childhood cancer survivors.

Recent findings

With advances in oncologic treatment, growing numbers of childhood cancer survivors are now able to consider pregnancy. A significant proportion of survivors have received cardiotoxic therapy, particularly anthracyclines, and/or chest radiation. Cardiomyopathy is the most common cardiac complication of cancer-directed therapy; pericardial disease, valvular disease, premature coronary artery disease, and conduction abnormalities are other potential sequelae. In female survivors of childhood malignancy, cardiac evaluation should be performed prior to pregnancy as subclinical disease has the potential to be unmasked by the hemodynamic stress of pregnancy. However, limited data exist on pregnancy outcomes after cancer survivorship.

Summary

With appropriate management, maternal and fetal outcomes in pregnancy following childhood cancer are generally favorable. Further research is needed to understand the incidence of cardiac complications among childhood cancer survivors, strategies to prevent these complications, optimal cardiovascular management during pregnancy and the postpartum period, and on the impact of pregnancy itself on the natural history of treatment-related cardiotoxicity.

     

Variation in Screening Abnormality Rates and Follow-Up of Breast,Cervical and Colorectal Cancer Screening within the PROSPR Consortium

Background

Primary care providers and health systems have prominent roles in guiding effective cancer screening.

Objective

To characterize variation in screening abnormality rates and timely initial follow-up for common cancer screening tests.

Design

Population-based cohort undergoing screening in 2011, 2012, or 2013 at seven research centers comprising the National Cancer Institute-sponsored Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium.

Participants

Adults undergoing mammography with or without digital breast tomosynthesis (n = 97,683 ages 40–75 years), fecal occult blood or fecal immunochemical tests (n = 759,553 ages 50–75 years), or Papanicolaou with or without human papillomavirus tests (n = 167,330 ages 21–65 years).

Intervention

Breast, colorectal, or cervical cancer screening.

Main Measures

Abnormality rates per 1000 screens; percentage with timely initial follow-up (within 90 days, except 9-month window for BI-RADS 3). Primary care clinic-level variation in percentage with screening abnormality and percentage with timely initial follow-up.

Key Results

There were 10,248/97,683 (104.9 per 1000) abnormal breast cancer screens, 35,847/759,553 (47.2 per 1000) FOBT/FIT-positive colorectal cancer screens, and 13,266/167,330 (79.3 per 1000) abnormal cervical cancer screens. The percentage with timely follow-up was 93.2 to 96.7 % for breast centers, 46.8 to 68.7  % for colorectal centers, and 46.6 % for the cervical cancer screening center (low-grade squamous intraepithelial lesions or higher). The primary care clinic variation (25th to 75th percentile) was smaller for the percentage with an abnormal screen (breast, 8.5–10.3 %; colorectal, 3.0–4.8 %; cervical, 6.3–9.9 %) than for the percentage with follow-up within 90 days (breast, 90.2–95.8 %; colorectal, 43.4–52.0 %; cervical, 29.6–61.4 %).

Conclusions

Variation in both the rate of screening abnormalities and their initial follow-up was evident across organ sites and primary care clinics. This highlights an opportunity for improving the delivery of cancer screening through focused study of patient, provider, clinic, and health system characteristics associated with timely follow-up of screening abnormalities.

     

Metachronous colorectal cancer

Aim

In this study, we present our patients with metachronous colorectal cancer.

Patients and methods

In the period between 1990 and 2009, 670 patients with colorectal cancer were treated.

Results

Metachronous cancer was developed in 4 (0.6%) patients. The time interval between index and metachronous cancer was 28 months to 22 years (mean 146 months).

Conclusion

Metachronous colorectal cancer is a potential risk that proves the necessity of postoperative colonoscopic control of all patients with colorectal cancer.

     

Assessment of Serum sTREM-1 as a Marker of Subclinical Inflammation in Diarrhea-Predominant Patients with Irritable Bowel Syndrome

Background

Irritable bowel disease (IBS) is viewed upon as a functional disorder of subclinical inflammatory changes in recent years, and there is no reliable biomarker. Triggering receptor expressed on myeloid cells 1 (TREM-1), also produced in a soluble form (sTREM-1), is involved in the activation of inflammatory cascades of intracellular events and may play a role in pathogenesis of IBS.

Aim

To investigate whether serum sTREM-1 level can be used as a marker of subclinical inflammation in D-IBS.

Methods

Abdominal pain was quantified by a validated questionnaire. Expression level of TREM-1 in colonic mucosa as well as sTREM-1 level in serum was also detected. Furthermore, we investigated the involvement of TREM-1-associated macrophage activation in IBS-like visceral hypersensitivity.

Results

No evidence for obvious inflammation was found in D-IBS patients. Serum sTREM-1 level in D-IBS patients was significantly higher than that in HCs, which was also significantly correlated with abdominal pain scores. We showed a marked increase in the proportion of TREM-1-expressing macrophages in D-IBS, which was significantly correlated with abdominal pain scores. Functionally, gadolinium chloride (GdCl₃), a macrophage selective inhibitor, or LP17, the TREM-1-specific peptide, significantly suppressed the visceral hypersensitivity in trinitrobenzene sulfonic acid (TNBS)-treated mice with IBS-like visceral hypersensitivity.

Conclusions

Serum sTREM-1 level is significantly higher in D-IBS patients and positively correlates with abdominal pain, which may be initiated by TREM-1-associated macrophage activation, indicating the existence of subclinical inflammation in D-IBS. Therefore, serum sTREM-1 is a potential marker of subclinical inflammation in D-IBS.

     

Cardiovascular Risk in Breast Cancer Patients Receiving Estrogen or Progesterone Antagonists

Purpose of review

The purpose of this review is to summarize the current literature on estrogen and progesterone antagonists and their effects on the cardiovascular system.

Recent findings

Estrogen and progesterone antagonists reduce cancer-related recurrence and mortality in women with ER-positive breast cancer. Recent studies, however, suggest that women with early stage breast cancer are more likely to die of cardiovascular disease than recurrent breast cancer. Estrogen antagonists have been shown to reduce endothelial function, to increase lipid profiles and to alter body composition accelerating atherosclerotic changes.

Summary

While clinical trial data demonstrates mixed results of the impact of estrogen antagonists on cardiovascular risk, there is a growing body of evidence that estrogen suppression and estrogen antagonists result in biologic effects on the endothelium, altering lipid profiles and accelerating the risk of atherosclerosis. Further longitudinal work however is needed.

     

Cancer Risk Communication with Low Health Literacy Patients: A Continuing Medical Education Program

BACKGROUND

Low health literacy (HL) is an important risk factor for cancer health disparities.

OBJECTIVE

Describe a continuing medical education (CME) program to teach primary care physicians (PCP) cancer risk communication and shared decision-making (SDM) with low HL patients and baseline skills assessment.

DESIGN

Cluster randomized controlled trial in five primary care clinics in New Orleans, LA.

PARTICIPANTS

Eighteen PCPs and 73 low HL patients overdue for cancer screening.

INTERVENTION

Primary care physicians completed unannounced standardized patient (SP) encounters at baseline. Intervention physicians received SP verbal feedback; academic detailing to review cancer screening guidelines, red flags for identifying low HL, and strategies for effective counseling; and web-based tutorial of SP comments and checklist items hyperlinked to reference articles/websites.

MAIN MEASURES

Baseline PCP self-rated proficiency, SP ratings of physician general cancer risk communication and SDM skills, patient perceived involvement in care.

RESULTS

Baseline assessments show physicians rated their proficiency in discussing cancer risks and eliciting patient preference for treatment/decision-making as “very good”. SPs rated physician exploration of perceived cancer susceptibility, screening barriers/motivators, checking understanding, explaining screening options and associated risks/benefits, and eliciting preferences for screening as “satisfactory”. Clinic patients rated their doctor’s facilitation of involvement in care and information exchange as “good”. However, they rated their participation in decision-making as “poor”.

DISCUSSION

The baseline skills assessment suggests a need for physician training in cancer risk communication and shared decision making for patients with low HL. We are determining the effectiveness of teaching methods, required resources and long-term feasibility for a CME program.

     

Association Between Primary Care Visits and Colorectal Cancer Screening Outcomes in the Era of Population Health Outreach

Background

Population outreach strategies are increasingly used to improve colorectal cancer (CRC) screening. The influence of primary care on cancer screening in this context is unknown.

Objective

To assess associations between primary care provider (PCP) visits and receipt of CRC screening and colonoscopy after a positive fecal immunochemical (FIT) or fecal occult blood test (FOBT).

Design

Population-based cohort study.

Participants

A total of 968,072 patients ages 50–74 years who were not up to date with CRC screening in 2011 in four integrated healthcare systems (three with screening outreach programs using FIT kits) in the Population-Based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium.

Measures

Demographic, clinical, PCP visit, and CRC screening data were obtained from electronic health records and administrative databases. We examined associations between PCP visits in 2011 and receipt of FIT/FOBT, screening colonoscopy, or flexible sigmoidoscopy (CRC screening) in 2012 and follow-up colonoscopy within 3 months of a positive FIT/FOBT in 2012. We used multivariable logistic regression and propensity score models to adjust for confounding.

Results

Fifty-eight percent of eligible patients completed a CRC screening test in 2012, most by FIT. Those with a greater number of PCP visits had higher rates of CRC screening at all sites. Patients with ≥1 PCP visit had nearly twice the adjusted-odds of CRC screening (OR?=?1.88, 95 % CI: 1.86–1.89). Overall, 79.6 % of patients with a positive FIT/FOBT completed colonoscopy within 3 months. Patients with ≥1 PCP visit had 30 % higher adjusted odds of completing colonoscopy after positive FIT/FOBT (OR?=?1.30; 95 % CI: 1.22–1.40).

Conclusions

Patients with a greater number of PCP visits had higher rates of both incident CRC screening and colonoscopy after positive FIT/FOBT, even in health systems with active population health outreach programs. In this era of virtual care and population outreach, primary care visits remain an important mechanism for engaging patients in cancer screening.

     

The Role of Cardiovascular Magnetic Resonance in Sports Cardiology; Current Utility and Future Perspectives

Purpose of review

Cardiovascular magnetic resonance (CMR) is frequently used in the investigation of suspected cardiac disease in athletes. In this review, we discuss how CMR can be used in athletes with suspected cardiomyopathy with particular reference to volumetric analysis and tissue characterization. We also discuss the finding of non-ischaemic fibrosis in athletes describing its prevalence, distribution and clinical importance.

Recent findings

The strengths of CMR include high spatial resolution, unrestricted imaging planes and lack of ionizing radiation. Regular physical exercise leads to cardiac remodeling that in certain situations can be clinically challenging to differentiate from various cardiomyopathies. Thorough morphological assessment by CMR is fundamental to ensuring accurate diagnosis. Developments in tissue characterization by late gadolinium enhancement and T1 mapping have the potential to be powerful additional tools in this challenging clinical situation. Using late gadolinium enhancement, it is also possible to detect non-ischaemic fibrosis in athletes who do not have overt cardiomyopathy. The mechanisms of this fibrosis are unclear; however, it does appear to be clinically important. We also review data on the prevalence of non-ischaemic fibrosis in athletes.

Summary

CMR is a powerful tool to aid in the diagnosis of cardiomyopathy in athletes. It may also have a future role in assessing fibrosis related to long-term participation in sport.