Cost-effectiveness of using protons in breast cancer patients aiming at reducing cardiotoxicity: A risk-stratification analysis

Purpose Incidental exposure of heart to ionizing irradiation is associated with an increased risk of ischemic heart disease (IHD) in breast cancer patients after radiotherapy. Intensity-modulated proton radiation therapy (IMPT) offers a promise in limiting the mean heart dose (MHD) in breast irradiation to a negligible level. However, the uncertainty in cost-effectiveness hinders its use. This cost-effectiveness analysis aims to identify patients in appropriate risk groups as targets for IMPT. Methods A Markov decision model was designed to evaluate the cost-effectiveness of IMPT versus intensity-modulated photon-radiation therapy (IMRT) in reducing the irradiation-related IHD risk. Baseline evaluation was performed on 50-year-old women patient without preexisting cardiac risk factor (CRF). Stratified for preexisting cardiac risk and photon MHD, cost-effective scenarios under different proton cost and willingness-to-pay (WTP) were identified for 40-, 50- and 60-year-old patients. Results With baseline set-ups, incremental effectiveness (IE) ranged from 0.025 quality-adjusted life-year (QALY) to 0.135 QALY when photon MHD varied from 3 to 16 Gy; IE increased from 0.043 QALY to 0.964 QALY when preexisting cardiac risk increased from the baseline level to its 10 times. IMPT was not cost-effective to patients without preexisting CRF. At the WTP of China, once proton cost reduced to $20,000, IMPT would be cost-effective to ≤ 50-year-old women patients having preexisting cardiac risk of general-population level. Conclusion Patient’s preexisting cardiac risk level should be a main consideration for the clinical decision of using protons; protons may become cost-effective to general-level patients if a substantial decrease in proton cost occurs in the future.

Coronary endothelial dysfunction appears to be a manifestation of a systemic process: A report from the Women’s Ischemia Syndrome Evaluation – Coronary Vascular Dysfunction (WISE-CVD) study

Background Coronary microvascular dysfunction (CMD) is prevalent in symptomatic women with ischemia but no obstructive coronary artery disease (INOCA). Urine albumin-creatinine ratio (UACR) is a measure of renal microvascular endothelial dysfunction. Both are predictors of adverse cardiovascular events. It is unknown if CMD could be a manifestation of a systemic process. We evaluated the relationship between renal microvascular dysfunction and CMD as measured by invasive coronary function testing (CFT). Methods and results We measured urine albumin and creatinine to provide UACR in 152 women enrolled in the Women’s Ischemia Syndrome Evaluation–Coronary Vascular Dysfunction (WISE-CVD) study (2008–2015) with suspected INOCA who underwent CFT. Invasive CFT measures of endothelial and non-endothelial dependent coronary microvascular function were obtained. Subjects were divided into those with detectable (≥20 mg/g) and undetectable urine albumin (<20 mg/g). The group mean age was 54 ± 11 years, with a moderate cardiac risk factor burden including low diabetes prevalence, and a mean UACR of 12 ± 55 mg/g (range 9.5–322.7 mg/g). Overall, coronary endothelial-dependent variables (change in coronary blood flow and coronary diameter in response to cold pressor testing) had significant inverse correlations with log UACR (r = -0.17, p = 0.05; r = -0.18, p = 0.03, respectively). Conclusions Among women with INOCA and relatively low risk factor including diabetes burden, renal microvascular dysfunction, measured by UACR, is related to coronary endothelial-dependent CMD. These results suggest that coronary endothelial-dependent function may be a manifestation of a systemic process. Enhancing efferent arteriolar vasodilatation in both coronary endothelial-dependent function and renal microvascular dysfunction pose potential targets for investigation and treatment. Clinical trial registration https://clinicaltrials.gov/ct2/show/NCT00832702.

Causal Associations of Urate With Cardiovascular Risk Factors: Two-Sample Mendelian Randomization

BackgroundMendelian Randomization (MR) studies show conflicting causal associations of genetically predicted serum urate with cardiovascular risk factors (i.e., hypertension, diabetes, lipid profile, and kidney function). This study aimed to robustly investigate a causal relationship between urate and cardiovascular risk factors considering single nucleotide polymorphisms (SNPs) as instrumental variables using two-sample MR and various sensitivity analyses.MethodsData on SNP-urate associations were taken from the Global Urate Genetics Consortium and data on SNP-cardiovascular risk factor associations were taken from various consortia/UK Biobank. SNPs were selected by statistically and biologically driven approaches as instrumental variables. Various sensitivity analyses were performed using different MR methods including inverse variance weighted, MR-Egger, weighted median/mode, MR-PRESSO, and the contamination mixture method.ResultsThe statistically driven approach showed significant causal effects of urate on HDL-C and triglycerides using four of the six MR methods, i.e., every 1 mg/dl increase in genetically predicted urate was associated with 0.047 to 0.103 SD decrease in HDL-C and 0.034 to 0.207 SD increase in triglycerides. The biologically driven approach to selection of SNPs from ABCG2, SLC2A9, SLC17A1, SLC22A11, and SLC22A12 showed consistent causal effects of urate on HDL-C from all methods with 0.038 to 0.057 SD decrease in HDL-C per 1 mg/dl increase of urate, and no evidence of horizontal pleiotropy was detected.ConclusionOur study suggests a significant and robust causal effect of genetically predicted urate on HDL-C. This finding may explain a small proportion (7%) of the association between increased urate and cardiovascular disease but points to urate being a novel cardiac risk factor.

POS0215 DIRECT AND CONDITIONAL EFFECTS OF EPICARDIAL ADIPOSE TISSUE VOLUME ON CORONARY PLAQUE PROGRESSION IN RHEUMATOID ARTHRITIS

Background:Epicardial adipose tissue volume (EATv) predicts coronary atherosclerosis presence, progression and cardiovascular event risk in general patients1,2. Our group recently reported that EATv associated with greater subclinical coronary plaque burden, non-calcified plaque presence and vulnerable plaque characteristics in patients with rheumatoid arthritis (RA). The relationship was stronger in RA patients with lower disease duration, no traditional cardiac risk factors, and who were not obese.Objectives:To evaluate the predictive value of EATv on long-term coronary atherosclerosis development, and moderators of the association between EATv and plaque formation.Methods:This single-center observational cohort study included 100 patients without symptoms or diagnosis of cardiovascular disease who underwent computed tomography angiography for evaluation of EATv and coronary atherosclerosis at baseline and repeat assessments 6.9±0.3 years later to evaluate plaque progression. New plaque formation in segments without plaque at baseline was the main outcome. Robust multivariable logistic regression evaluated the effect of high versus low EATv (based on median) on likelihood of new plaque formation, accounting for clustering of segments within patients. Potential moderator effects of prespecified predictors were also assessed.Results:High EATv (>107 cm3) predicted new plaque formation in segments without baseline plaque (OR 2.77 [95% CI 1.43-5.37], p= 0.003); however, significance was lost in the multivariable model. Importantly, high EATv associated with formation of higher-risk non- and partially calcified plaque after adjusting for Framingham D’Agostino risk score, obesity, segment location, time-averaged CRP, duration of bDMARD and statin treatment and cumulative prednisone dose (adjusted OR 2.57 [95% CI 1.02-6.48], p= 0.045). RA duration (<10 versus >10 years), cardiac risk factor burden (≤1 versus >1), presence of mixed/calcified plaque in other coronary segments at baseline, and statin exposure (≤1 versus >1 year, based on median) moderated the effect of EATv on all new plaque formation (all p for interaction ≤ 0.021). Specifically, high EATv predicted new plaque formation in patients with RA duration <10 years (adjusted OR 5.75 [95% CI 1.77-18.67]), those with ≤1 cardiac risk factors (adjusted OR 3.40 [95% CI 1.46-7.90]), those without calcification at baseline (adjusted OR 2.65 [95% CI 1.11-6.31]) and those with statin treatment <1 year (adjusted OR 3.33 [95% CI 1.13-9.77]). This was not the case for patients with RA >10 years, ≥ 2 cardiac risk factors, calcification at baseline and statin treatment >1 year (figure 1).Conclusion:High baseline EATv independently predicted future higher-risk non-calcified and mixed coronary plaque in RA. Moreover, it conditionally promoted new plaque formation overall in patients with earlier disease, low cardiac risk factor burden, who had little or no atherosclerosis at baseline and who had limited exposure to statin therapy. These findings indicate the need for a larger prospective evaluation of the role of EATv as a biomarker of coronary atherosclerosis development in RA.References:[1]Hwang I-C et al. J Atheroscler Thromb 2017;24:262–74. 2. Ding J et al. Am J Clin Nutr 2009;90:499–504.Figure 1.Moderators of influence of EATv on new coronary plaque formationDisclosure of Interests:George Karpouzas Speakers bureau: Sanofi/ Genzyme/ Regeneron, Consultant of: Sanofi/ Genzyme/ Regeneron, Grant/research support from: Pfizer, Sarah Ormseth: None declared, Elizabeth Hernandez: None declared, Matthew Budoff Consultant of: Pfizer

Electrocardiographic features in males: a cross sectional study in Prayagraj District, Uttar Pradesh

Background: The electrocardiogram (ECG) is the graphical display of the various electrical changes of the heart. It plays an important role in the diagnosis of various heart diseases. It is one of the methods of assessing the effects of hypertension on one of its target organ heart. It remains one of the most sensitive methods for establishing left ventricular hypertrophy (LVH) and is often abnormal even when there is no left ventricular heave and chest x-ray shows no classical or obvious left ventricular enlargement. The study was done with objective to asses the Electrocardiographic features of male which were ≥ 30 years in Urban and Rural Prayagraj.Methods: A community based cross-sectional study was carried out in Prayagraj District. Study participants were 620 males, 310 urban and 310 rural of age equal or above 30 years and study sampling technique were two stage random sampling. The data was collected by using predesigned, pretested, semi structured questionnaire and analyzed by using SPSS 23.0 version.Results: LVH is a marker of severity of hypertension. It is an important cardiac risk factor and it has a substantial clinical significance on the course of cardiovascular events in terms of morbidity and mortality.Conclusions: Left ventricular hypertrophy, a cardinal manifestation of hypertensive cardiac damage.

Efficacy of team-based collaborative care for distressed patients in secondary prevention of chronic coronary heart disease (TEACH): study protocol of a multicenter randomized controlled trial

Background Coronary heart disease (CHD) is the leading cause of death and years of life lost worldwide. While effective treatments are available for both acute and chronic disease stages there are unmet needs for effective interventions to support patients in health behaviors required for secondary prevention. Psychosocial distress is a common comorbidity in patients with CHD and associated with substantially reduced health-related quality of life (HRQoL), poor health behavior, and low treatment adherence. Methods In a confirmatory, randomized, controlled, two-arm parallel group, multicenter behavioral intervention trial we will randomize 440 distressed CHD patients with at least one insufficiently controlled cardiac risk factor to either their physicians' usual care (UC) or UC plus 12-months of blended collaborative care (TeamCare = TC). Trained nurse care managers (NCM) will proactively support patients to identify individual sources of distress and risk behaviors, establish a stepwise treatment plan to improve self-help and healthy behavior, and actively monitor adherence and progress. Additional e-health resources are available to patients and their families. Intervention fidelity is ensured by a treatment manual, an electronic patient registry, and a specialist team regularly supervising NCM via videoconferences and recommending protocol and guideline-compliant treatment adjustments as indicated. Recommendations will be shared with patients and their physicians who remain in charge of patients’ care. Since HRQoL is a recommended outcome by both, several guidelines and patient preference we chose a ≥ 50% improvement over baseline on the HeartQoL questionnaire at 12 months as primary outcome. Our primary hypothesis is that significantly more patients receiving TC will meet the primary outcome criterion compared to the UC group. Secondary hypotheses will evaluate improvements in risk factors, psychosocial variables, health care utilization, and durability of intervention effects over 18–30 months of follow-up. Discussion TEACH is the first study of a blended collaborative care intervention simultaneously addressing distress and medical CHD risk factors conducted in cardiac patients in a European health care setting. If proven effective, its results can improve long-term chronic care of this vulnerable patient group and may be adapted for patients with other chronic conditions. Trial registration: German Clinical Trials Register, DRKS00020824, registered on 4 June, 2020; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00020824

Stachys sieboldii Miq. Root Attenuates Weight Gain and Dyslipidemia in Rats on a High-Fat and High-Cholesterol Diet

This study aimed at investigating the anti-obesity and anti-dyslipidemic effects of Stachys sieboldii Miq. root (SS) powder in rats following a high-fat and high-cholesterol (HFC) diet for 6 weeks. Thirty-two Sprague–Dawley rats were fed one of the following diets: a regular diet (RD), HFC, HFC supplemented with 3% SS (HFC + 3SS) or HFC supplemented with 5% SS (HFC + 5SS). Following an HFC diet increased body weight (BW) gain (p < 0.001) and the food efficiency ratio (FER; p < 0.001); however, SS consumption gradually prevented the HFC-induced BW gain (p < 0.001) and increase in FER (p < 0.01). The HFC diet resulted in increased liver size (p < 0.001) and total adipose tissue weight (p < 0.001), whereas the SS supplementation decreased hepatomegaly (p < 0.05) and body fat mass (p < 0.001). SS consumption prevented the increased activities of serum alanine aminotransferase (ALT; p < 0.001), aspartate aminotransferase (AST; p < 0.001), alkaline phosphatase (ALP; p < 0.01 in HFC + 5SS) and lactate dehydrogenase (LDH; p < 0.001 in HFC + 5SS) induced by the HFC diet (p < 0.001). The SS supplementation improved lipid profiles in the circulation by lowering triglyceride (TG; p < 0.01), total cholesterol (TC; p < 0.001) and non-HDL cholesterol (non-HDL-C; p < 0.001) levels, as well as the atherogenic index (p < 0.01) and cardiac risk factor (p < 0.01). The lipid distribution in the liver (p < 0.05) and white adipose tissues (WAT; p < 0.001) of the HFC + SS diet-consuming rats was remarkably lower than that of the HFC diet-consuming rats. The average size of the epididymal adipose tissue (p < 0.001) was significantly lower in the HFC + SS diet-fed rats than in the HFC diet-fed rats. The fecal lipid (>3% SS; p < 0.001) and cholesterol (5% SS; p < 0.001) efflux levels were significantly elevated by the SS supplementation compared to those measured in the RD or HFC diet-fed groups. In addition, the hepatic lipid and cholesterol metabolism-related gene expressions were affected by SS consumption, as the hepatic anabolic gene expression (Acc; p < 0.001, Fas; p < 0.001 and G6pdh; p < 0.01) was significantly attenuated. The HFC + 5SS diet-fed rats exhibited elevated hepatic Cyp7a1 (p < 0.001), Hmgcr (p < 0.001) and Ldlr (p < 0.001) mRNA expression levels compared to the HFC diet-fed rats. These results suggest that SS may possess anti-adipogenic and lipid-lowering effects by enhancing lipid and cholesterol efflux in mammals.

The landscape of cardiovascular care in pediatric cancer patients and survivors: a survey by the ACC Pediatric Cardio-Oncology Work Group

Objective To enhance the understanding of cardiovascular care delivery in childhood cancer patients and survivors. Study design A 20-question survey was created by the Pediatric Cardio-oncology Work Group of the American College of Cardiology (ACC) Cardio-oncology Section to assess the care, management, and surveillance tools utilized to manage pediatric/young adult cardio-oncology patients. The survey distribution was a collaborative effort between Cardio-oncology Section and membership of the Adult Congenital and Pediatric Cardiology Section (ACPC) of the ACC. Results Sixty-five individuals, all self-identified as physicians, responded to the survey. Most respondents (n = 58,89%) indicated childhood cancer patients are regularly screened prior to and during cancer therapy at their centers, predominantly by electrocardiogram (75%), standard echocardiogram (58%) and advanced echocardiogram (50%) (i.e. strain, stress echo). Evaluation by a cardiologist prior to/during therapy was reported by only 8(12%) respondents, as compared to post-therapy which was reported by 28 (43%, p < 0.01). The most common indications for referral to cardiology at pediatric centers were abnormal test results (n = 31,48%) and history of chemotherapy exposure (n = 27,42%). Of note, during post-treatment counseling, common cardiovascular risk-factors like blood pressure (31,48%), lipid control (22,34%), obesity & smoking (30,46%) and diet/exercise/weight loss (30,46%) were addressed by fewer respondents than was LV function (72%). Conclusions The survey data demonstrates that pediatric cancer patients are being screened by EKG and/or imaging prior to/during therapy at most centers. Our data, however, highlight the potential for greater involvement of a cardiovascular specialist for pre-treatment evaluation process, and for more systematic cardiac risk factor counseling in posttreatment cancer survivors.