The Association Between C24:0/C16:0 Ceramide Ratio and Cardiorespiratory Fitness is Robust to Effect Modifications by Age and Sex.

Ceramides and cardiorespiratory (CR) fitness are both related to cardiovascular diseases. The associations of three blood plasma ceramides (C16:0, C22:0, and C24:0) with CR fitness in the population-based Study of Health in Pomerania (SHIP-START-1; n = 1,102; mean age 50.3 years, 51.5% women) are investigated. In addition, subgroup analysis according to age (

Female-specific pancreatic cancer survival from CT imaging of visceral fat implicates glutathione metabolism in solid tumors.

RATIONALE AND OBJECTIVES: To identify if body composition, assessed with preoperative CT-based visceral fat ratio quantification as well as tumor metabolic gene expression, predicts sex-dependent overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: This was a retrospective analysis of preoperative CT in 98 male and 107 female patients with PDAC. Relative visceral fat (rVFA; visceral fat normalized to total fat) was measured automatically using software and corrected manually. Median and optimized rVFA thresholds were determined according to published methods. Kaplan Meier and log-rank tests were used to estimate OS. Multivariate models were developed to identify interactions between sex, rVFA, and OS. Unsupervised gene expression analysis of PDAC tumors from The Cancer Genome Atlas (TCGA) was performed to identify metabolic pathways with similar survival patterns to rVFA. RESULTS: Optimized preoperative rVFA threshold of 38.9% predicted significantly different OS in females with a median OS of 15 months (above threshold) vs 24 months (below threshold; p = 0.004). No significant threshold was identified in males. This female-specific significance was independent of age, stage, and presence of chronic pancreatitis (p = 0.02). Tumor gene expression analysis identified female-specific stratification from a five-gene signature of glutathione S-transferases. This was observed for PDAC as well as clear cell renal carcinoma and glioblastoma. CONCLUSION: CT-based assessments of visceral fat can predict pancreatic cancer OS in females. Glutathione S-transferase expression in tumors predicts female-specific OS in a similar fashion.

Intensive Versus Traditional Cardiac Rehabilitation: Mortality and Cardiovascular Outcomes in a 2016-2020 Retrospective Medicare Cohort.

BACKGROUND: Traditional cardiac rehabilitation (CR) improves cardiovascular outcomes and reduces mortality, but less is known about the relative benefit of intensive CR (ICR) which incorporates greater lifestyle education through 72 sessions (versus 36 in CR). Our objective was to determine whether ICR is associated with a mortality and cardiovascular benefit compared with CR. METHODS: Retrospective cohort study of Medicare Fee-For-Service beneficiaries in a 100% sample, claims data set. Qualifying events were captured from May 1, 2016 to December 31, 2019 and ICR/CR utilization captured from May 1, 2016 to December 31, 2020. Among patients attending at least 1 day of either CR or ICR, Cox proportional hazards models using a 1 to 5 propensity score match were used to compare utilization and the association of ICR versus CR participation with (1) all-cause mortality and (2) cardiovascular-related hospitalizations or nonfatal cardiac events. Dose-response was assessed by the number of days attended. RESULTS: From 2016 to 2019, 1 277 358 unique patients met at least one qualifying indication for ICR/CR from 2016 to 2019. Of these, 262 579 (20.6%) and 4452 (0.4%) attended at least one session of CR or ICR, respectively (mean [SD] age, 73.2 [7.8] years; 32.3% female). In the matched sample, including 26 659 total patients (median, 2.4-year follow-up), ICR was associated with 12% lower all-cause mortality (multivariable adjusted hazard ratio, 0.88 [95% CI, 0.78-0.99]; P=0.036) compared with CR but no significant difference for cardiovascular-related hospitalization or nonfatal cardiac events. The mortality benefit was seen for both ICR and CR per day strata, with each modality demonstrating a clear dose-response benefit. CONCLUSIONS: ICR is associated with lower mortality than traditional CR among Medicare beneficiaries but no difference in cardiovascular-related hospitalization or nonfatal cardiac events. Moreover, ICR and CR demonstrate a dose-response relationship for mortality. Additional studies are needed to confirm these observations and to better understand the mechanisms by which ICR may lead to a reduction in mortality.

The inorganic NItrate and eXercise performance in Heart Failure (iNIX-HF) phase II clinical trial: Rationale and study design.

Background: Heart failure (HF) is a debilitating and often fatal disease that affects millions of people worldwide. Diminished nitric oxide synthesis, signaling, and bioavailability are believed to contribute to poor skeletal muscle function and aerobic capacity. The aim of this clinical trial (iNIX-HF) is to determine the acute and longer-term effectiveness of inorganic nitrate supplementation on exercise performance in patients with HF with reduced ejection fraction (HFrEF). Methods: This clinical trial is a double-blind, placebo-controlled, randomized, parallel-arm design study in which patients with HFrEF (n = 75) are randomized to receive 10 mmol potassium nitrate (KNO3) or a placebo capsule daily for 6 wk. Primary outcome measures are muscle power determined by isokinetic dynamometry and peak aerobic capacity (VO2peak) determined during an incremental treadmill exercise test. Endpoints include the acute effects of a single dose of KNO3 and longer-term effects of 6 wk of KNO3. The study is adequately powered to detect expected increases in these outcomes at P < 0.05 with 1-ß>0.80. Discussion: The iNIX-HF phase II clinical trial will evaluate the effectiveness of inorganic nitrate supplements as a new treatment to ameliorate poor exercise capacity in HFrEF. This study also will provide critical preliminary data for a future 'pivotal', phase III, multi-center trial of the effectiveness of nitrate supplements not only for improving exercise performance, but also for improving symptoms and decreasing other major cardiovascular endpoints. The potential public health impact of identifying a new, relatively inexpensive, safe, and effective treatment that improves overall exercise performance in patients with HFrEF is significant.

Safety, tolerability, and effectiveness of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin in combination with standard chemotherapy for patients with advanced, inoperable pancreatic adenocarcinoma: a phase 1b observational study.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Thus, there is an urgent need for safe and effective novel therapies. PDAC's excessive reliance on glucose metabolism for its metabolic needs provides a target for metabolic therapy. Preclinical PDAC models have demonstrated that targeting the sodium-glucose co-transporter-2 (SGLT2) with dapagliflozin may be a novel strategy. Whether dapagliflozin is safe and efficacious in humans with PDAC is unclear. METHODS: We performed a phase 1b observational study (ClinicalTrials.gov ID NCT04542291; registered 09/09/2020) to test the safety and tolerability of dapagliflozin (5 mg p.o./day × 2 weeks escalated to 10 mg p.o./day × 6 weeks) added to standard Gemcitabine and nab-Paclitaxel (GnP) chemotherapy in patients with locally advanced and/or metastatic PDAC. Markers of efficacy including Response Evaluation Criteria in Solid Tumors (RECIST 1.1) response, CT-based volumetric body composition measurements, and plasma chemistries for measuring metabolism and tumor burden were also analyzed. RESULTS: Of 23 patients who were screened, 15 enrolled. One expired (due to complications from underlying disease), 2 dropped out (did not tolerate GnP chemotherapy) during the first 4 weeks, and 12 completed. There were no unexpected or serious adverse events with dapagliflozin. One patient was told to discontinue dapagliflozin after 6 weeks due to elevated ketones, although there were no clinical signs of ketoacidosis. Dapagliflozin compliance was 99.4%. Plasma glucagon increased significantly. Although abdominal muscle and fat volumes decreased; increased muscle-to-fat ratio correlated with better therapeutic response. After 8 weeks of treatment in the study, partial response (PR) to therapy was seen in 2 patients, stable disease (SD) in 9 patients, and progressive disease (PD) in 1 patient. After dapagliflozin discontinuation (and chemotherapy continuation), an additional 7 patients developed the progressive disease in the subsequent scans measured by increased lesion size as well as the development of new lesions. Quantitative imaging assessment was supported by plasma CA19-9 tumor marker measurements. CONCLUSIONS: Dapagliflozin is well-tolerated and was associated with high compliance in patients with advanced, inoperable PDAC. Overall favorable changes in tumor response and plasma biomarkers suggest it may have efficacy against PDAC, warranting further investigation.

Prospective Study of the Impact of Outpatient Intensive Cardiac Rehabilitation on Diet Quality, Health-related Quality of Life, and Cardiovascular Health Indices.

Intensive cardiac rehabilitation (ICR) programs are approved by the Centers for Medicare & Medicaid Services on the basis of their expected benefits for cardiovascular disease (CVD) risk factors and health outcomes. However, the impact of outpatient ICR on diet quality, quality of life (QOL), and CVD risk factors has not been prospectively assessed. The aim of this cohort study was to test the hypothesis that patients enrolled in a Pritikin outpatient ICR program would show improved diet quality, QOL, and CVD health indexes, and that the improvements would be greater than those of patients in traditional cardiac rehabilitation (CR). Patients enrolled in ICR (n = 230) or CR (n = 62) were assessed at baseline and at visit 24. Diet quality was assessed using the Rate Your Plate questionnaire, and QOL was assessed through the Dartmouth COOP Functional Health Assessment questionnaire. Secondary end points included anthropometrics, CVD biomarkers, hemodynamics, and fitness. Patients in ICR programs displayed significant improvements at visit 24 versus baseline in Rate Your Plate and Dartmouth COOP Functional Health Assessment scores, weight, body mass index (BMI), waist circumference, fat mass, total and low-density lipoprotein cholesterol, 6-minute walk distance, and grip strength. Patients in ICR had greater improvements in diet quality (p = 0.001), weight (p = 0.001), and BMI (p <0.001) than did those in CR. In summary, this prospective study of Pritikin outpatient ICR revealed significant improvements in diet quality, QOL, adiposity, and other CVD risk factors. The improvements in diet quality, body weight, and BMI were greater than those observed with traditional CR.

A prospective cohort study of the impact of outpatient Intensive Cardiac Rehabilitation on depression and cardiac self-efficacy.

Study objective: To evaluate whether an Intensive Cardiac Rehabilitation (ICR) program improves depression and cardiac self-efficacy among patients with a qualifying cardiac diagnosis. Design: Prospective, longitudinal cohort design. Setting: Single-center, tertiary referral, outpatient cardiac rehabilitation center. Participants: Patients with a qualifying diagnosis for ICR. Interventions: Outpatient ICR. Main outcome measures: Mental health, as assessed using the Patient Health Questionnaire-9 (PHQ-9) and cardiac self-efficacy using the Cardiac Self-Efficacy (CSE) scale. Results: Of the 268 patients included (median age 69 y, 73% men), 70% had no depressive symptoms at baseline (PHQ-9 score <5). PHQ-9 scores improved in the overall sample (p < 0.0001), with greater improvements among patients with mild depressive symptoms at baseline (-4 points, p < 0.001) and those with moderate to severe depressive symptoms at baseline (-5.5 points, p < 0.001). Cardiac self-efficacy improved overall, and the two subsections of the cardiac self-efficacy questionnaire titled, "maintain function" and "control symptoms" improved (all p < 0.001). Conclusions: Participation in an outpatient ICR program is associated with fewer depressive symptoms and greater cardiac self-efficacy among patients with CVD who qualify for ICR. The improvement in depression was greatest for those with moderate to severe depressive symptoms.

Risk of nonalcoholic fatty liver disease and associations with gastrointestinal cancers.

Metabolic syndrome may contribute to the rising incidence of multiple gastrointestinal (GI) cancers in recent birth cohorts. However, other than hepatocellular carcinoma, the association between nonalcoholic fatty liver disease (NAFLD) and risk of non-liver GI cancers is unexplored. We prospectively examined the associations of NAFLD risk with GI cancers among 319,290 participants in the UK Biobank (2006-2019). Baseline risk for NAFLD was estimated using the Dallas Steatosis Index, a validated prediction tool. Multivariable Cox models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) according to NAFLD risk categories: low (<20%), intermediate (20%-49%), and high (≥50%). We also examined the associations by age of cancer diagnosis (earlier onset [<60] vs. ≥60). A total of 273 incident liver cancer and 4789 non-liver GI cancer cases were diagnosed. Compared with individuals at low risk for NAFLD, those at high risk had 2.41-fold risk of liver cancer (RR = 2.41, 95% CI: 1.73-3.35) and 23% increased risk of non-liver GI cancers (RR = 1.23, 95% CI: 1.14-1.32) (all ptrend < 0.001). Stronger associations were observed for men and individuals who were obese (all pinteraction < 0.05). NAFLD-associated elevated risk was stronger for earlier-onset cancers. For each 25% increase in NAFLD risk, the RRs for earlier-onset cancers were 1.32 (95% CI: 1.05-1.66) for esophageal cancer, 1.35 (95% CI: 1.06-1.72) for gastric cancer, 1.34 (95% CI: 1.09-1.65) for pancreatic cancer, and 1.10 (95% CI: 1.01-1.20) for colorectal cancer. Conclusion: NAFLD risk was associated with an increased risk of liver and most GI cancers, especially those of earlier onset.

Benefits of the First Pritikin Outpatient Intensive Cardiac Rehabilitation Program.

PURPOSE: Intensive cardiac rehabilitation (ICR) is a comprehensive, medically supervised exercise treatment program covered by Medicare for patients with approved cardiac diagnoses. The aim of this study was to determine the benefits of the first Pritikin outpatient ICR program. METHODS: This retrospective analysis included patients referred to ICR or traditional cardiac rehabilitation (CR) during the first 7 yr (2013-2019) at the first facility to implement Pritikin ICR. Intensive cardiac rehabilitation is composed of 36 education sessions on nutrition, exercise, and a healthy mindset, in addition to 36 monitored exercise sessions that comprise traditional CR. Assessments included anthropometrics (weight, body mass index, and waist circumference), dietary patterns, physical function (6-min walk test, [6MWT] Short Physical Performance Battery [SPPB: balance, 4-m walk, chair rise], handgrip strength), and health-related quality of life (Dartmouth COOP, 36-item Short Form Survey). Baseline and follow-up measures were compared within and between groups. RESULTS: A total of 1963 patients enrolled (1507 ICR, 456 CR, 66.1 ± 11.4 yr, 68% male, 82% overweight or obese); 1141 completed the program (58%). The ICR patients completed 22 exercise and 18 education sessions in 9.6 wk; CR patients completed 19 exercise sessions in 10.3 wk. ICR resulted in improvements ( P < .001 pre vs post) in all anthropometric measures, dietary patterns, 6MWT distance, all SPPB components, grip strength, and health-related quality of life. The improvements in anthropometrics and dietary patterns were greater in ICR than in CR. CONCLUSIONS: The Pritikin outpatient ICR program promoted improvements in several cardiovascular health indices. Critical next steps are to assess long-term health outcomes after ICR, including cardiac events and mortality.

Metabolic Biomarkers Assessed with PET/CT Predict Sex-Specific Longitudinal Outcomes in Patients with Diffuse Large B-Cell Lymphoma.

In many cancers, including lymphoma, males have higher incidence and mortality than females. Emerging evidence demonstrates that one mechanism underlying this phenomenon is sex differences in metabolism, both with respect to tumor nutrient consumption and systemic alterations in metabolism, i.e., obesity. We wanted to determine if visceral fat and tumor glucose uptake with fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) could predict sex-dependent outcomes in patients with diffuse large B-cell lymphoma (DLBCL). We conducted a retrospective analysis of 160 patients (84 males; 76 females) with DLBCL who had imaging at initial staging and after completion of therapy. CT-based relative visceral fat area (rVFA), PET-based SUVmax normalized to lean body mass (SULmax), and end-of-treatment FDG-PET 5PS score were calculated. Increased rVFA at initial staging was an independent predictor of poor OS only in females. At the end of therapy, increase in visceral fat was a significant predictor of poor survival only in females. Combining the change in rVFA and 5PS scores identified a subgroup of females with visceral fat gain and high 5PS with exceptionally poor outcomes. These data suggest that visceral fat and tumor FDG uptake can predict outcomes in DLBCL patients in a sex-specific fashion.

Skeletal Muscle Contractile Function in Heart Failure With Reduced Ejection Fraction-A Focus on Nitric Oxide.

Despite advances over the past few decades, heart failure with reduced ejection fraction (HFrEF) remains not only a mortal but a disabling disease. Indeed, the New York Heart Association classification of HFrEF severity is based on how much exercise a patient can perform. Moreover, exercise capacity-both aerobic exercise performance and muscle power-are intimately linked with survival in patients with HFrEF. This review will highlight the pathologic changes in skeletal muscle in HFrEF that are related to impaired exercise performance. Next, it will discuss the key role that impaired nitric oxide (NO) bioavailability plays in HFrEF skeletal muscle pathology. Lastly, it will discuss intriguing new data suggesting that the inorganic nitrate 'enterosalivary pathway' may be leveraged to increase NO bioavailability via ingestion of inorganic nitrate. This ingestion of inorganic nitrate has several advantages over organic nitrate (e.g., nitroglycerin) and the endogenous nitric oxide synthase pathway. Moreover, inorganic nitrate has been shown to improve exercise performance: both muscle power and aerobic capacity, in some recent small but well-controlled, cross-over studies in patients with HFrEF. Given the critical importance of better exercise performance for the amelioration of disability as well as its links with improved outcomes in patients with HFrEF, further studies of inorganic nitrate as a potential novel treatment is critical.

Coronary circulatory function with increasing obesity: A complex U-turn.

AIMS: The aim of this investigation was to explore and characterize alterations in coronary circulatory function in function of increasing body weight with medically controlled cardiovascular risk factors and, thus, "metabolically" unhealthy obesity. MATERIALS AND METHODS: We prospectively enrolled 106 patients with suspected CAD but with normal stress-rest myocardial perfusion on 13 N-ammonia PET/CT and with medically controlled or no cardiovascular risk factors. 13 N-ammonia PET/CT concurrently determined myocardial blood flow (MBF) during pharmacologically induced hyperaemia and at rest. Based on body mass index (BMI), patients were grouped into normal weight (BMI: 20.0-24.9 kg/m2 , n = 22), overweight (BMI: 25.0-29.9 kg/m2 , n = 27), obese (BMI: 30.0-39.9 kg/m2 , n = 31), and morbidly obese (BMI ≥ 40kg/m2 , n = 26). RESULTS: Resting MBF was comparable among groups (1.09 ± 0.18 vs. 1.00 ± 0.15 vs. 0.96 ± 0.18 vs.. 1.06 ± 0.31 ml/g/min; p = .279 by ANOVA). Compared to normal weight individuals, the hyperaemic MBF progressively decreased in in overweight and obese groups, respectively (2.54 ± 0.48 vs. 2.02 ± 0.27 and 1.75 ± 0.39 ml/g/min; p < .0001), while it increased again in the group of morbidly obese individuals comparable to normal weight (2.44 ± 0.41 vs. 2.54 ± 0.48 ml/g/min, p = .192). The BMI of the study population correlated with the hyperaemic MBF in a quadratic or U-turn fashion (r = .34, SEE = 0.46; p ≤ .002). CONCLUSIONS: The U-turn of hyperaemic MBF from obesity to morbid obesity is likely to reflect contrasting effects of abdominal versus subcutaneous adipose tissue on coronary circulatory function indicative of two different disease entities, but needing further investigations.

Intensive Cardiac Rehabilitation Is Markedly Underutilized by Medicare Beneficiaries: RESULTS FROM A 2012-2016 NATIONAL SAMPLE.

PURPOSE: Intensive cardiac rehabilitation (ICR) was developed to enhance traditional cardiac rehabilitation (CR) by adding sessions focused on nutrition, lifestyle behaviors, and stress management. Intensive CR has been Medicare-approved since 2010, yet little is known about national utilization rates of ICR in the Medicare population or characteristics associated with its use. METHODS: A 5% sample of Medicare claims data from 2012 to 2016 was used to identify beneficiaries with a qualifying indication for ICR/CR and to quantify utilization of ICR or CR within 1 yr of the qualifying diagnosis. RESULTS: From 2012 to 2015, there were 107 246 patients with a qualifying indication. Overall, only 0.1% of qualifying patients participated in ICR and 16.2% in CR from 2012 to 2016, though utilization rates of both ICR and CR increased during this period (ICR 0.06 to 0.17%, CR 14.3 to 18.2%). The number of ICR centers increased from 15 to 50 over the same period. There were no differences between ICR and CR enrollees with respect to age, sex, race, discharge location, median income, dual enrollment, or number of comorbidities. Compared with eligible beneficiaries who did not attend ICR or CR, those who attended either program were younger, more likely to be male and White, and had higher median income. CONCLUSIONS: Although ICR and CR have a class 1 indication for the treatment of cardiovascular disease and the number of ICR centers has increased, ICR is not widely available and remains markedly underutilized. Continued research is needed to understand the barriers to program development and patient participation.

Modified Application of Cardiac Rehabilitation in Older Adults (MACRO) Trial: Protocol changes in a pragmatic multi-site randomized controlled trial in response to the COVID-19 pandemic.

BACKGROUND: Older adults are at higher risk for cardiovascular disease and functional decline, often leading to deterioration and dependency. Cardiac rehabilitation (CR) provides opportunity to improve clinical and functional recovery, yet participation in CR decreases with age. Modified Application of CR in Older Adults (MACRO) is a National Institute on Aging (NIA)-funded pragmatic trial that responds to this gap by aiming to increase enrollment of older adults into CR and improving functional outcomes. This article describes the methodology and novel features of the MACRO trial. METHODS: Randomized, controlled trial of a coaching intervention (MACRO-I) vs. usual care for older adults (age ≥ 70 years) eligible for CR after an incident cardiac hospitalization. MACRO-I incorporates innovations including holistic risk assessments, flexible CR format (i.e., helping patients to select a CR design that aligns with their personal risks and preferences), motivational prompts, nutritional emphasis, facilitated deprescription, enhanced education, and home visits. Key modifications were necessitated by the COVID-19 pandemic, including switching from a performance-based primary endpoint (Short Physical Performance Battery) to a patient-reported measure (Activity Measure for Post-Acute Care Computerized Adaptive Testing). Changes prompted by COVID-19 maintain the original intent of the trial and provide key methodologic advantages. CONCLUSIONS: MACRO is exploring a novel individualized coaching intervention to better enable older patients to participate in CR. Due to COVID-19 many aspects of the MACRO protocol required modification, but the primary objective of the trial is maintained and the updated protocol will more effectively achieve the original goals of the study.

Links between ceramides and cardiac function.

PURPOSE OF REVIEW: Total ceramide levels in cardiac tissue relate to cardiac dysfunction in animal models. However, emerging evidence suggests that the fatty acyl chain length of ceramides also impacts their relationship to cardiac function. This review explores evidence regarding the relationship between ceramides and left ventricular dysfunction and heart failure. It further explores possible mechanisms underlying these relationships. RECENT FINDINGS: In large, community-based cohorts, a higher ratio of specific plasma ceramides, C16 : 0/C24 : 0, related to worse left ventricular dysfunction. Increased left ventricular mass correlated with plasma C16 : 0/C24 : 0, but this relationship became nonsignificant after adjustment for multiple comparisons. Decreased left atrial function and increased left atrial size also related to C16 : 0/C24 : 0. Furthermore, increased incident heart failure, overall cardiovascular disease (CVD) mortality and all-cause mortality were associated with higher C16 : 0/C24 : 0 (or lower C24 : 0/C16 : 0). Finally, a number of possible biological mechanisms are outlined supporting the link between C16 : 0/C24 : 0 ceramides, ceramide signalling and CVD. SUMMARY: High cardiac levels of total ceramides are noted in heart failure. In the plasma, C16 : 0/C24 : 0 ceramides may be a valuable biomarker of preclinical left ventricular dysfunction, remodelling, heart failure and mortality. Continued exploration of the mechanisms underlying these profound relationships may help develop specific lipid modulators to combat cardiac dysfunction and heart failure.

Quantification of myocardial oxygen extraction fraction: A proof-of-concept study.

PURPOSE: To demonstrate a proof of concept for the measurement of myocardial oxygen extraction fraction (mOEF) by a cardiovascular magnetic resonance technique. METHODS: The mOEF measurement was performed using an electrocardiogram-triggered double-echo asymmetric spin-echo sequence with EPI readout. Seven healthy volunteers (22-37 years old, 5 females) were recruited and underwent the same imaging scans at rest on 2 different days for reproducibility assessment. Another 5 subjects (23-37 years old, 4 females) underwent cardiovascular magnetic resonance studies at rest and during a handgrip isometric exercise with a 25% of maximal voluntary contraction. Both mOEF and myocardial blood volume values were obtained in septal regions from respective maps. RESULTS: The reproducibility was excellent for the measurements of mOEF in septal myocardium (coefficient of variation: 3.37%) and moderate for myocardial blood volume (coefficient of variation: 19.7%). The average mOEF and myocardial blood volume of 7 subjects at rest were 0.61 ± 0.05 and 11.0 ± 4.3%, respectively. The mOEF agreed well with literature values that were measured by PET in healthy volunteers. In the exercise study, there was no significant change in mOEF (0.61 ± 0.06 vs 0.62 ± 0.07) or myocardial blood volume (12 ± 6% vs 13 ± 4%) from rest to exercise, as expected. CONCLUSION: The implemented cardiovascular magnetic resonance method shows potential for the quantitative assessment of mOEF in vivo. Future technical work is needed to improve image quality and to further validate mOEF measurements.