Endometrial cancer survivors' perceptions of their cardiovascular disease risk (results from WF-1804CD AH-HA).

OBJECTIVE: Despite considerable burden of cardiovascular disease (CVD), data on endometrial cancer survivors' CVD perceptions are lacking. We assessed survivors' perspectives on addressing CVD risk during oncology care. METHODS: This cross-sectional analysis utilized data from an ongoing trial of an EHR heart health tool (R01CA226078 & UG1CA189824) conducted through the NCI Community Oncology Research Program (NCORP, WF-1804CD). Endometrial cancer survivors post-potentially curative treatment were recruited from community practices and completed a pre-visit baseline survey, including American Heart Association Simple 7 CVD factors. Likert-type questions assessed confidence in understanding CVD risk, CVD risk perception, and desired discussion during oncology care. Medical record abstraction ascertained data on CVD and cancer characteristics. RESULTS: Survivors (N = 55, median age = 62; 62% 0-2 years post-diagnosis) were predominately white, non-Hispanic (87%). Most agreed/strongly agreed heart disease poses a risk to their health (87%) and oncology providers should talk to patients about heart health (76%). Few survivors reported smoking (12%) but many had poor/intermediate values for blood pressure (95%), body mass index (93%), fasting glucose/A1c (60%), diet (60%), exercise (47%) and total cholesterol (53%). 16% had not seen a PCP in the last year; these survivors were more likely to report financial hardship (22% vs 0%; p = 0.02). Most reported readiness to take steps to maintain or improve heart health (84%). CONCLUSIONS: Discussions of CVD risk during routine oncology care are likely to be well received by endometrial cancer survivors. Strategies are needed to implement CVD risk assessment guidelines and to enhance communication and referrals with primary care. Clinical Trials #: NCT03935282.

Cardioprotective medication use in Black and white breast cancer survivors.

PURPOSE: Racial disparities in cardiovascular disease and cardiac dysfunction exist amongst breast cancer survivors. This study examined the prevalence of cardioprotective medication use in survivors and identified factors associated with use by race. METHODS: The analysis included women enrolled in the Women's Hormonal Initiation and Persistence study, a longitudinal observational trial of breast cancer survivors. The study outcome, angiotensin converting enzyme inhibitor (ACEi) or ß-Blocker (BB) use, were ascertained from pharmacy records. Demographic, psychosocial, healthcare, and quality of life factors were collected from surveys and clinical data were abstracted from medical records. Bivariate associations by race and ACEi/BB use were tested using chi square and t tests; logistic regression evaluated multivariable-adjusted associations. RESULTS: Of the 246 survivors in the sample, 33.3% were Black and most were < 65 years of age (58.4%). Most survivors were hypertensive (57.6%) and one-third received ACEi/BBs. In unadjusted analysis, White women (vs. Black) (OR 0.33, 95% 0.19-0.58) and women with higher ratings of functional wellbeing (OR 0.94, 95% 0.89-0.99) were less likely to use ACEi/BBs. Satisfaction with provider communication was only significant for White women. In multivariable-adjusted analysis, ACEi/BB use did not differ by race. Correlates of ACEi/BB use included hypertension among all women and older age for Black women only. CONCLUSIONS: After adjusting for age and comorbidities, no differences by race in ACEi/BB use were observed. Hypertension was a major contributor of ACEi/BB use in BC survivors.

Information maximizing component analysis of left ventricular remodeling due to myocardial infarction.

BACKGROUND: Although adverse left ventricular shape changes (remodeling) after myocardial infarction (MI) are predictive of morbidity and mortality, current clinical assessment is limited to simple mass and volume measures, or dimension ratios such as length to width ratio. We hypothesized that information maximizing component analysis (IMCA), a supervised feature extraction method, can provide more efficient and sensitive indices of overall remodeling. METHODS: IMCA was compared to linear discriminant analysis (LDA), both supervised methods, to extract the most discriminatory global shape changes associated with remodeling after MI. Finite element shape models from 300 patients with myocardial infarction from the DETERMINE study (age 31-86, mean age 63, 20 % women) were compared with 1991 asymptomatic cases from the MESA study (age 44-84, mean age 62, 52 % women) available from the Cardiac Atlas Project. IMCA and LDA were each used to identify a single mode of global remodeling best discriminating the two groups. Logistic regression was employed to determine the association between the remodeling index and MI. Goodness-of-fit results were compared against a baseline logistic model comprising standard clinical indices. RESULTS: A single IMCA mode simultaneously describing end-diastolic and end-systolic shapes achieved best results (lowest Deviance, Akaike information criterion and Bayesian information criterion, and the largest area under the receiver-operating-characteristic curve). This mode provided a continuous scale where remodeling can be quantified and visualized, showing that MI patients tend to present larger size and more spherical shape, more bulging of the apex, and thinner wall thickness. CONCLUSIONS: IMCA enables better characterization of global remodeling than LDA, and can be used to quantify progression of disease and the effect of treatment. These data and results are available from the Cardiac Atlas Project ( http://www.cardiacatlas.org ).

Mechanism of decreased sensitivity of dobutamine associated left ventricular wall motion analyses for appreciating inducible ischemia in older adults.

BACKGROUND: Dobutamine associated left ventricular (LV) wall motion analyses exhibit reduced sensitivity for detecting inducible ischemia in individuals with increased LV wall thickness. This study was performed to better understand the mechanism of this reduced sensitivity in the elderly who often manifest increased LV wall thickness and risk factors for coronary artery disease. METHODS: During dobutamine cardiovascular magnetic resonance (DCMR) stress testing, we assessed rate pressure product (RPP), aortic pulse wave velocity (PWV), LV myocardial oxygen demand (pressure volume area, PVA, mass, volumes, concentricity, and the presence of wall motion abnormalities (WMA) and first pass gadolinium enhanced perfusion defects (PDs) indicative of ischemia in 278 consecutively recruited individuals aged 69 ± 8 years with pre-existing or known risk factors for coronary artery disease. Each variable was assessed independently by personnel blinded to participant identifiers and analyses of other DCMR or hemodynamic variables. RESULTS: Participants were 80% white, 90% hypertensive, 43% diabetic and 55% men. With dobutamine, 60% of the participants who exhibited PDs had no inducible WMA. Among these participants, myocardial oxygen demand was lower than that observed in those who had both wall motion and perfusion abnormalities suggestive of ischemia (p = 0.03). Relative to those with PDs and inducible WMAs, myocardial oxygen demand remained different in these individuals with PDs without an inducible WMA after accounting for LV afterload and contractility (p = 0.02 and 0.03 respectively), but not after accounting for either LV stress related end diastolic volume index (LV preload) or resting concentricity (p = 0.31-0.71). CONCLUSIONS: During dobutamine stress testing, elderly patients experience increased LV concentricity and declines in LV preload and myocardial oxygen demand, all of which are associated with an absence of inducible LV WMAs indicative of myocardial ischemia. These findings provide insight as to why dobutamine associated wall motion analyses exhibit reduced sensitivity for identifying inducible ischemia in elderly. TRIAL REGISTRATION: This study was registered with Clinicaltrials.gov (NCT00542503).

Right ventricular stress-induced perfusion defects and late gadolinium enhancement in coronary artery disease.

OBJECTIVE: The assessment of right ventricular (RV) perfusion defects has remained challenging during vasodilator stress perfusion with cardiovascular magnetic resonance (CMR). The significance of RV signal abnormalities during vasodilator stress perfusion and late gadolinium-enhanced CMR is yet uncertain. METHODS: Among 61 individuals who underwent adenosine CMR stress testing before cardiac catheterization, we assessed the severity of coronary artery stenoses, mortality, the presence of stress and rest perfusion defects, as well as the presence of late gadolinium enhancement (LGE). RESULTS: Right ventricular stress-induced perfusion defects were positively associated with left anterior descending artery and proximal right coronary artery stenoses but were negatively associated with left circumflex artery stenoses. The presence of RVLGE was associated with mortality, but 77% of those with RVLGE also had left ventricular LGE. CONCLUSIONS: Proximal right coronary artery and left anterior descending artery stenoses are positively associated, whereas left circumflex artery stenoses are negatively associated with RV stress-induced perfusion defects. Right ventricular LGE was associated with mortality, but further study is needed to determine whether this is independent of left ventricular LGE.

Small, short-duration, dobutamine-induced perfusion defects are not associated with adverse prognosis in intermediate-risk individuals receiving cardiovascular magnetic resonance stress imaging.

OBJECTIVE: The objective of this study was to assess the frequency and prognostic utility of small, short-duration left ventricular myocardial perfusion defects during dobutamine cardiovascular magnetic resonance (DCMR) stress imaging. METHODS: We performed first-pass contrast-enhanced DCMR at peak stress in 331 consecutively recruited individuals (aged 68 ± 8 years, 50% men) at intermediate risk for a future cardiac event. Size, location, and persistence of low-signal intensity perfusion defects were recorded. Cardiac events were assessed by personnel blinded to imaging results for a median of 24 months after the DCMR. RESULTS: Among the 55 individuals (16.6%) who exhibited small (<25% myocardial thickness) and short-duration (<5 frames in persistence) perfusion defects, diabetes was more prevalent (P = 0.019) and no cardiac events were observed. Large, persistent perfusion defects were associated with coronary artery disease, prior myocardial infarction, and decreased left ventricular function (P < 0.001 for all) and increased 2-year risk for a cardiac event (hazard ratio, 10.3; P < 0.001; confidence interval, 3.3-33.0). CONCLUSIONS: In individuals with diabetes, hypertension, or coronary artery disease at intermediate risk for a future cardiac event, small, short-duration DCMR perfusion defects are not associated with increased 2-year risk for a subsequent cardiac event.

Hypertension Severity and Declines in Left Ventricular Ejection Fraction Among Women Receiving Adjuvant Chemotherapy for Breast Cancer (WF-97415 UPBEAT).

BACKGROUND: Hypertension is a risk factor for experiencing left ventricular ejection fraction (LVEF) declines during receipt of potentially cardiotoxic breast cancer (BC) treatment. We sought to determine whether the hypertension stage is associated with LVEF decline during BC treatment. METHODS: Across 24 centers, cardiac magnetic resonance measures of LVEF and brachial arterial blood pressure (BP) measurements were performed in women with stages I to III BC before and 3 months after initiating potentially cardiotoxic chemotherapy. Using multivariable analysis, we assessed in a blinded fashion the association between 3-month ΔLVEF and precancer treatment American Heart Association/American College of Cardiology stages of hypertension. RESULTS: Among 204 women, age averaged 56±1 years with 75% being White and 20% of Black race. Participants received anthracycline (45.6%), trastuzumab (22.5%), cyclophosphamide (52.9%), or paclitaxel (50%). After accounting for pretreatment LVEF, diabetes status, tobacco use, age, the number of antihypertensive medications, and body mass index, those with stage II hypertension experienced an LVEF decline of -2.89% ([95% CI, -0.69% to -5.19%]; P=0.01) relative to individuals with normal BP. Other stages saw nonsignificant declines relative to normal BP to elevated BP (-1.63% [95% CI, -0.62% to 3.88%]; P=0.16) and stage I hypertension (-0.94% [95% CI, -0.90% to 2.78%]; P=0.32). CONCLUSIONS: Compared with women receiving treatment for BC with normal BP, there is a stronger association of decline in LVEF in women with stage II hypertension relative to women with other hypertension stages. This raises the possibility that stage along with hypertension presence may be associated with an increased risk for the LVEF decline among women receiving potentially cardiotoxic chemotherapy for BC. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02791581 and NCT01719562.

Left ventricular remodeling in premature ventricular contraction-induced cardiomyopathy: Effect of coupling intervals and atrioventricular dissociation.

Background: Left ventricular dyssynchrony (LVD) and postextrasystolic potentiation (PESP) associated with premature ventricular contractions (PVCs) may play a role in the development of premature ventricular contraction-induced cardiomyopathy (PVC-CM). Long-coupled (LC) PVCs have a greater LVD than short-coupled (SC) PVCs, whereas SC-PVCs have a stronger PESP than LC-PVCs. Objective: The purpose of this study was to compare SC-PVCs and LC-PVCs to evaluate the roles of LVD, PESP, and atrioventricular dissociation (AVD) in the development of PVC-CM. Methods: Thirty-six canines underwent pacemaker implantation to induce bigeminal right ventricular apical epicardial PVCs (50% burden) for 12 weeks. Telemetry assessed PVC burden and AVD. Animals were grouped as SC-PVC (coupling interval [CI] 200-220ms), LC-PVC (CI 330 ms), or sham (control). Echocardiographic changes, AVD, and hemodynamics were monitored for 12 weeks. Results: PVC burden was similar between SC-PVC and LC-PVC groups but was statistically higher in the SC-PVC group (50% vs 47.5%; P = .028). After 12 weeks, left ventricular ejection fraction (LVEF) significantly decreased in both SC-PVC and LC-PVC groups (47.1% ± 1.4% and 45.5% ± 2%, respectively) compared to sham group (61% ± 1.6%; P <.001). Overall AVD was similar between SC-PVC and LC-PVC groups, and there was no significant correlation between AVD and reduction in LVEF at 12 weeks (r = 0.09, P = .5; and r = 0.06, P = .8, respectively). Additionally, both SC-PVC and LC-PVC groups experienced substantial declines in max and min dP/dt after 12 weeks compared to baseline. Conclusion: Neither PVC CI nor AVD played an independent role in the development or severity of PVC-CM. LVD and PESP make equal relative contributions to the development of PVC-CM.

Simultaneous measurement of left and right ventricular volumes and ejection fraction during dobutamine stress cardiovascular magnetic resonance.

OBJECTIVE: During cardiovascular stress, if right ventricular (RV) stroke volume exceeds left ventricular (LV) stroke volume, then a large volume of blood is displaced into the pulmonary circulation that may precipitate pulmonary edema. We sought to determine the metrics by which cardiovascular magnetic resonance (CMR) could measure simultaneous displacement of RV and LV stroke volumes during dobutamine stress. METHODS: Thirteen healthy subjects (5 women) aged 53 ± 10 years without medical conditions and taking no medications underwent 2 CMR examinations at 1.5 T separated by 4 to 8 weeks in which RV and LV stroke volumes were determined during intravenous dobutamine and atropine infused to achieve 80% of the maximum predicted heart rate response for age. RESULTS: The RV and LV stroke volumes were highly correlated at each level of stress (rest: r = 0.98, P = 0.007; low stress: r = 0.87, P = 0.001; and peak stress: r = 0.88, P = 0.001), and the mean difference in SV at each level of stress (rest, low stress, and peak stress was 0 to 2 mL on examinations 1 and 2. CONCLUSIONS: Simultaneous change in right and left ventricular stroke volumes can be assessed in a highly reproducible manner throughout the course of dobutamine CMR stress administered to achieve 80% of maximum predicted heart rate response for age. This technology may help identify discrepancies in RV and LV stroke volumes during cardiovascular stress that are associated with the development of pulmonary edema.

Myocardial Function in Premenopausal Women Treated With Ovarian Function Suppression and an Aromatase Inhibitor.

Background: Premenopausal women with high-risk hormone receptor (HR)-positive breast cancer often receive ovarian function suppression (OFS) with aromatase inhibitor therapy; however, abrupt menopause induction, together with further decrements in estrogen exposure through aromatase inhibition, may affect cardiovascular microcirculatory function. We examined adenosine-induced changes in left ventricular (LV) myocardial T1, a potential subclinical marker of LV microcirculatory function in premenopausal women undergoing treatment for breast cancer. Methods: Twenty-one premenopausal women (14 with HR-positive breast cancer receiving OFS with an aromatase inhibitor and 7 comparator women with triple-negative breast cancer [TNBC] who had completed primary systemic therapy) underwent serial resting and adenosine cardiovascular magnetic resonance imaging measurements of LV myocardial T1 and LV volumes, mass, and ejection fraction. All statistical tests were 2-sided. Results: After a median of 4.0 months (range = 3.1-5.7 months), the stress to resting ratio of LV myocardial T1 declined in women with HR-positive breast cancer (-1.3%, 95% confidence interval [CI] = -3.4% to 0.7%) relative to those with TNBC (3.2%, 95% CI = -1.2% to 7.6%, P = .02). After accounting for age, LV stroke volume, LV ejection fraction, diastolic blood pressure, and breast cancer subtype women with HR-positive breast cancer experienced a blunted T1 response after adenosine relative to women with TNBC (difference = -4.7%, 95% CI = -7.3% to -2.1%, P difference = .002). Conclusions: Over the brief interval examined, women with HR-positive breast cancer receiving OFS with an aromatase inhibitor experienced reductions in adenosine-associated changes in LV myocardial T1 relative to women who received nonhormonal therapy for TNBC. These findings suggest a possible adverse impact on LV myocardial microcirculatory function in premenopausal women with breast cancer receiving hormone deprivation therapy.

Both intermuscular fat and LVEF decline promote heart failure symptoms in cancer survivors.

BACKGROUND: Approximately 20% of cancer survivors treated with chemotherapy experience worsening heart failure (HF) symptoms post-cancer treatment. While research has predominantly investigated the role of cardiotoxic treatments, much less attention has focused on other risk factors, such as adiposity. However, emerging data in cancer survivors indicates that adiposity may also impact a variety of cardiovascular outcomes. METHODS: In a prospective study of 62 patients diagnosed with cancer followed for 24 months from cancer diagnosis through to survivorship (post-cancer treatment), we ascertained baseline fat depots including intermuscular fat (IMF) of the erector spinae muscles; and pre- and post-cancer treatment left ventricular ejection fraction (LVEF) and HF symptoms at baseline and 24-months, respectively. Linear regression was used to model independent variables in relation to HF symptoms at 24-months. RESULTS: Baseline IMF and LVEF change over 24-months significantly interacted to predict HF score at 24-months. The highest HF symptom score was observed for participants who experienced high IMF at baseline and a high decline in LVEF over 24-months (HF score = 11.0) versus all other categories of baseline IMF and LVEF change. CONCLUSIONS: Together IMF and LVEF decline may play an important role in the worsening of HF symptoms in cancer survivors. The finding that IMF at cancer diagnosis led to elevated HF scores post-treatment suggests that IMF may be a potential target for intervention studies.

Assessment of Coronary Artery Calcium Scoring to Guide Statin Therapy Allocation According to Risk-Enhancing Factors: The Multi-Ethnic Study of Atherosclerosis.

Importance: The 2018 American Heart Association/American College of Cardiology Guideline on the Management of Blood Cholesterol recommends the use of risk-enhancing factor assessment and the selective use of coronary artery calcium (CAC) scoring to guide the allocation of statin therapy among individuals with an intermediate risk of atherosclerotic cardiovascular disease (ASCVD). Objective: To examine the association between risk-enhancing factors and incident ASCVD by CAC burden among those at intermediate risk of ASCVD. Design, Setting, and Participants: The Multi-Ethnic Study of Atherosclerosis is a multicenter population-based prospective cross-sectional study conducted in the US. Baseline data for the present study were collected between July 15, 2000, and July 14, 2002, and follow-up for incident ASCVD events was ascertained through August 20, 2015. Participants were aged 45 to 75 years with no clinical ASCVD or diabetes at baseline, were at intermediate risk of ASCVD (≥7.5% to <20.0%), and had a low-density lipoprotein cholesterol level of 70 to 189 mg/dL. Exposures: Family history of premature ASCVD, premature menopause, metabolic syndrome, chronic kidney disease, lipid and inflammatory biomarkers, and low ankle-brachial index. Main Outcomes and Measures: Incident ASCVD over a median follow-up of 12.0 years. Results: A total of 1688 participants (mean [SD] age, 65 [6] years; 976 men [57.8%]). Of those, 648 individuals (38.4%) were White, 562 (33.3%) were Black, 305 (18.1%) were Hispanic, and 173 (10.2%) were Chinese American. A total of 722 participants (42.8%) had a CAC score of 0. Among those with 1 to 2 risk-enhancing factors vs those with 3 or more risk-enhancing factors, the prevalence of a CAC score of 0 was 45.7% vs 40.3%, respectively. Over a median follow-up of 12.0 years (interquartile range [IQR], 11.5-12.6 years), the unadjusted incidence rate of ASCVD among those with a CAC score of 0 was less than 7.5 events per 1000 person-years for all individual risk-enhancing factors (with the exception of ankle-brachial index, for which the incidence rate was 10.4 events per 1000 person-years [95% CI, 1.5-73.5]) and combinations of risk-enhancing factors, including participants with 3 or more risk-enhancing factors. Although the individual and composite addition of risk-enhancing factors to the traditional risk factors was associated with improvement in the area under the receiver operating curve, the use of CAC scoring was associated with the greatest improvement in the C statistic (0.633 vs 0.678) for ASCVD events. For incident ASCVD, the net reclassification improvement for CAC was 0.067. Conclusions and Relevance: In this cross-sectional study, among participants with CAC scores of 0, the presence of risk-enhancing factors was generally not associated with an overall ASCVD risk that was higher than the recommended treatment threshold for the initiation of statin therapy. The use of CAC scoring was associated with significant improvements in the reclassification and discrimination of incident ASCVD. The results of this study support the utility of CAC scoring as an adjunct to risk-enhancing factor assessment to more accurately classify individuals with an intermediate risk of ASCVD who might benefit from statin therapy.

Incidence and Survival by Human Epidermal Growth Factor Receptor 2 Status in Young Women With Stage I-III Breast Cancer: SEER, 2010-2016.

BACKGROUND: Young premenopausal women with breast cancer often experience more aggressive disease biology and poorer survival than older women. Diagnostic and therapeutic advances, including human epidermal growth factor receptor 2 (HER2)-directed therapy, may lessen treatment burden and improve survival for these young women, but contemporary incidence and survival data by HER2 status are limited. PATIENTS AND METHODS: We identified women aged 20-49 years (n = 68,530) diagnosed with stage I-III breast cancer during 2010-2016 from the United States Surveillance, Epidemiology, and End Results 18 registries database. Age-adjusted average annual percent changes in incidence (diagnosis 2010-2016) and 5-year Kaplan-Meier survival curves (diagnosis 2010-2015) were estimated by HER2 and hormone receptor (HR) status and stratified independently by cancer stage and race/ethnicity. RESULTS: With increasing age decade, proportions of HER2-/HR+ cancer increased, whereas proportions of HER2+/HR+, HER2+/HR-, and HER2-/HR- decreased. The greatest increases in incidence during 2010-2016 were observed for HER2+ among women aged 20-49 years and HER2-/HR- among women aged 20-29 years. Incidence decreased for HER2-/HR- among women aged 40-49 years. Five-year survival was lowest for HER2-/HR- status compared to other receptor-based subtypes among women aged 20-49 years. HER2+ status was more beneficial for 5-year survival than HR+ status among women aged 20-29 years, with the opposite observed among women aged 30-49 years, particularly those aged 40-49 years. CONCLUSION: HER2+ breast cancer increased among premenopausal women and was also associated with higher early survival within each HR status. HER2-/HR- cancer also increased among women aged 20-29 years and was associated with lower early survival. Our contemporary data provide important insights to help inform preventive and therapeutic strategies for premenopausal women.

Anthracycline-related cardiotoxicity in older patients with acute myeloid leukemia: a Young SIOG review paper.

The incidence of acute myeloid leukemia (AML) increases with age. Intensive induction chemotherapy containing cytarabine and an anthracycline has been part of the upfront and salvage treatment of AML for decades. Anthracyclines are associated with a significant risk of cardiotoxicity (especially anthracycline-related left ventricular dysfunction [ARLVD]). In the older adult population, the higher prevalence of cardiac comorbidities and risk factors may further increase the risk of ARLVD. In this article of the Young International Society of Geriatric Oncology group, we review the prevalence of ARLVD in patients with AML and factors predisposing to ARLVD, focusing on older adults when possible. In addition, we review the assessment of cardiac function and management of ARLVD during and after treatment. It is worth noting that only a minority of clinical trials focus on alternative treatment strategies in patients with mildly declined left ventricular ejection fraction or at a high risk for ARLVD. The limited evidence for preventive strategies to ameliorate ARLVD and alternative strategies to anthracycline use in the setting of cardiac comorbidities are discussed. Based on extrapolation of findings from younger adults and nonrandomized trials, we recommend a comprehensive baseline evaluation of cardiac function by imaging, cardiac risk factors, and symptoms to risk stratify for ARLVD. Anthracyclines remain an appropriate choice for induction although careful risk-stratification based on cardiac disease, risk factors, and predicted chemotherapy-response are warranted. In case of declined left ventricular ejection fraction, alternative strategies should be considered.

Relation of Low Normal Left Ventricular Ejection Fraction to Heart Failure Hospitalization in Blacks (From the Jackson Heart Study).

There is no clear consensus on a lower cutoff value for normal left ventricular ejection fraction (EF) and the prognostic implications of low normal EF (LNEF) are poorly understood, particularly in Blacks. Therefore, we investigated the association of LNEF and incident heart failure (HF) in a community-based cohort of Blacks. We studied 3,669 participants (mean age 54 years, 63% women) of the Jackson Heart Study without prevalent HF or coronary heart disease (CHD). Participants were divided into three groups: (1) Reduced EF (<50%), (2) LNEF (≥50%, <55%), and (3) Normal EF (≥55%). There were 197 cases of incident HF hospitalizations over a median follow-up of 10 years (interquartile range 9.4 to 10). After adjustment for conventional risk factors and incident CHD, the LNEF group had a higher rate of incident HF hospitalization than the Normal EF group (HR 1.58, 95% CI 1.04 to 2.38, p<0.05). Furthermore, this relation remained statistically significant after additionally adjusting for LV mass index but was not significant after adjusting for LV diastolic dysfunction grade. In participants with LNEF with incident HF, 63% developed HF with reduced EF and 37% developed HF with preserved EF. In conclusion, LNEF is associated with higher risk of incident HF hospitalization in comparison with normal EF in a community-based cohort of Blacks. In those with LNEF who went on to develop HF, most cases were HF with reduced EF. These findings suggest that strategies are needed for risk stratification and management to improve outcomes in patients with LNEF.

Determinants of Cardiorespiratory Fitness Following Thoracic Radiotherapy in Lung or Breast Cancer Survivors.

We measured peak oxygen consumption (VO2) in previous recipients of thoracic radiotherapy and assessed the determinants of cardiorespiratory fitness with an emphasis on cardiac and pulmonary function. Cancer survivors who have received thoracic radiotherapy with incidental cardiac involvement often experience impaired cardiorespiratory fitness, as measured by reduced peak VO2, a marker of impaired cardiovascular reserve. We enrolled 25 subjects 1.8 (0.1 to 8.2) years following completion of thoracic radiotherapy with significant heart exposure (at least 10% of heart volume receiving at least 5 Gray). All subjects underwent cardiopulmonary exercise testing, Doppler echocardiography, and circulating biomarkers assessment. The cohort included 16 Caucasians (64%), 15 women (60%) with a median age of 63 (59 to 66) years. The peak VO2 was 16.8 (13.5 to 21.9) ml·kg-1·min-1 or moderately reduced at 62% (50% to 93%) of predicted. The mean cardiac radiation dose was 5.4 (3.7 to 14.7) Gray, and it significantly correlated inversely with peak VO2 (R = -0.445, p = 0.02). Multivariate regression analysis revealed the diastolic functional reserve index and the N-terminal pro-brain natriuretic peptide (NTproBNP) serum levels were independent predictors of peak VO2 (ß = +0.813, p <0.01 and ß = -0.414, p = 0.04, respectively). In conclusion, patients who had received thoracic radiation display a dose-dependent relation between the cardiac radiation dose received and the impairment in peak VO2, the reduction in diastolic functional reserve index, and elevation of NTproBNP.

MRI of Cardiotoxicity.

Cardiovascular magnetic resonance (CMR) imaging is useful to identify systolic dysfunction, particularly when echocardiographic imaging is not acceptable because of poor acoustic windows or when left ventricular ejection fraction (LVEF) is inconclusive by other modalities and an accurate LVEF measurement is needed. Of particular advantage in cardio-oncology is CMR's capability to perform tissue characterization to noninvasively identify changes in pathologic conditions related to cancer therapy or to discriminate causes of disease that may confound presentation in cardio-oncology patients. For these reasons, there is an increasing use of CMR in the screening and surveillance of cardio-oncology patients.

Incidence and Survival Among Young Women With Stage I-III Breast Cancer: SEER 2000-2015.

BACKGROUND: Although recent findings suggest that de novo stage IV breast cancer is increasing in premenopausal women in the United States, contemporary incidence and survival data are lacking for stage I-III cancer. METHODS: Women aged 20-29 (n = 3826), 30-39 (n = 34 585), and 40-49 (n = 126 552) years who were diagnosed with stage I-III breast cancer from 2000 to 2015 were identified from the Surveillance, Epidemiology, and End Results 18 registries database. Age-adjusted, average annual percentage changes in incidence and 5- and 10-year Kaplan-Meier survival curves were estimated by race and ethnicity, stage, and hormone receptor (HR) status and grade (low to well and moderately differentiated; high to poorly and undifferentiated) for each age decade. RESULTS: The average annual percentage change in incidence was positive for each age decade and was highest among women aged 20-29 years. Increased incidence was driven largely by HR+ cancer, particularly HR+ low-grade cancer in women aged 20-29 and 40-49 years. By 2015, incidence of HR+ low- and high-grade cancer each independently exceeded incidence of HR- cancer in each age decade. Survival for HR+ low- and high-grade cancer decreased with decreasing age; survival for HR- cancer was similar across age decades. Among all women aged 20-29 years, 10-year survival for HR+ high-grade cancer was lower than that for HR+ low-grade or HR- cancer. Among women aged 20-29 years with stage I cancer, 10-year survival was lowest for HR+ high-grade cancer. CONCLUSIONS: HR+ breast cancer is increasing in incidence among premenopausal women, and HR+ high-grade cancer was associated with reduced survival among women aged 20-29 years. Our findings can help guide further evaluation of preventive, diagnostic, and therapeutic strategies for breast cancer among premenopausal women.

Effect of Intensive Blood Pressure Reduction on Left Ventricular Mass, Structure, Function, and Fibrosis in the SPRINT-HEART.

In observational studies, left ventricular mass (LVM) and structure are strong predictors of mortality and cardiovascular events. However, the effect of hypertension treatment on LVM reduction and its relation to subsequent outcomes is unclear, particularly at lower blood pressure (BP) targets. In an ancillary study of SPRINT (Systolic Blood Pressure Intervention Trial), where participants were randomly assigned to intensive BP control (target systolic BP target <120 mm Hg) versus standard BP control (<140 mm Hg), cardiac magnetic resonance imaging was performed at baseline and 18-month follow-up to measure: LVM, volumes, ejection fraction, and native T1 mapping for myocardial fibrosis. At baseline, 337 participants were examined (age: 64±9 years, 45% women); 300 completed the 18-month exam (153 intensive control and 147 standard control). In the intensive versus standard BP control group at 18 months, there was no difference in change in LVM (mean±SE =-2.7±0.5 g versus -2.3±0.7 g; P=0.368), ejection fraction, or native T1 (P=0.79), but there was a larger decrease in LVM/end-diastolic volume ratio (-0.04±0.01 versus -0.01±0.01; P=0.002) a measure of concentric LV remodeling. There were fewer cardiovascular events in the intensive control group, but no significant association between the reduced events and change in LVM or any other cardiac magnetic resonance imaging measure. In SPRINT-HEART, contrary to our hypothesis, there were no significant between-group differences in LVM, function, or myocardial T1 at 18-month follow-up. These results suggests that mediators other than these LV measures contribute to the improved cardiovascular outcomes with intensive BP control.

Predictive Value of Collagen Biomarkers for Heart Failure With and Without Preserved Ejection Fraction: MESA (Multi-Ethnic Study of Atherosclerosis).

BACKGROUND: Collagen biomarkers may correlate with incident heart failure (HF) and its subtypes. We hypothesized that circulating procollagen type III N-terminal propeptide (PIIINP) and collagen type I carboxy-terminal telopeptide (ICTP) predict incident HF. METHODS AND RESULTS: We used a stratified sampling design in a multiethnic sample of 3187 subjects, initially aged 45 to 84 years and free of cardiovascular disease. We assayed baseline serum PIIINP and ICTP concentrations using radioimmunoassay. Incident HF was adjudicated, distinguishing reduced ejection fraction (HFrEF; EF <45%) from preserved EF (HFpEF; EF ≥45%). The incidence density for HFpEF and HFrEF was computed using Poisson regression per SD for each of PIIINP and ICTP, adjusting in model 1 for age, race, sex, and renal function or in model 2 for these variables plus blood pressure and medication. Mean (SD) ICTP was 3.38±1.77 µg/L, and mean (SD) PIIINP was 5.48±2.04 µg/L. Among the HF cases, 96 were HFrEF and 107 were HFpEF. Neither ICTP nor PIIINP significantly predicted incident HFrEF. The incidence density for HFpEF per 100 people observed for 13 years was 1.65 for low PIIINP (lower 6 octiles) versus 3.00 for higher PIIINP (P=0.002) in model 1 and correspondingly 1.45 versus 2.59 (P=0.003) in model 2. For low ICTP (lower 7 octiles) versus higher ICTP (octile 8), incidence densities were 1.79 versus 3.64 (P=0.002) in model 1 and 1.58 versus 3.12 (P=0.002) in model 2. CONCLUSIONS: High levels of circulating ICTP and PIIINP as collagen biomarkers appear to be associated with incident HFpEF, but not HFrEF.