BACKGROUND:Hyperpolarized [1-13C]pyruvate cardiovascular magnetic resonance imaging (HP [1-13C]pyruvate CMR) visualizes key steps in myocardial metabolism. The present study aimed to examine patients with heart failure (HF) using HP [1-13C]pyruvate CMR. METHODS:A cross-sectional study of patients with HF and healthy controls using HP [1-13C]pyruvate CMR. Metabolic imaging was obtained using a cardiac-gated spectral-spatial excitation with spiral read-out acquisition. The metabolite signal was analyzed for lactate, bicarbonate, and the alanine signal. Metabolite signal was normalized to the total carbon signal (TC). At the 1-year follow-up, echocardiography was performed in all patients and HP [1-13C]pyruvate MRI in two patients. RESULTS:We included six patients with ischemic heart disease (IHD), six with dilated cardiomyopathy, and six healthy controls. In patients, left ventricular ejection fraction (LVEF) correlated with lactate/bicarbonate (r = -0.6, p = 0.03) and lactate/TC (r = -0.7, p = 0.01). In patients with LVEF <30%, lactate/TC was increased (p = 0.01) and bicarbonate/TC reduced (p = 0.03). Circumferential strain correlated with metabolite ratios: lactate/bicarbonate, r = 0.87 (p = 0.0002); lactate/TC, r = 0.85 (p = 0.0005); bicarbonate/TC, r = -0.82 (p = 0.001). In patients with IHD, a strong correlation was found between baseline metabolite ratios and the change in LVEF at follow-up: lactate/bicarbonate (p = 0.001), lactate/TC (p = 0.011), and bicarbonate/TC (p = 0.012). CONCLUSIONS:This study highlighted the ability of HP [1-13C]pyruvate CMR to detect changes in metabolism in HF. HP [1-13C]pyruvate CMR has the potential for metabolic phenotyping of patients with HF and for predicting treatment response. TRIAL REGISTRATION:EUDRACT, 2018-003533-15. Registered December 4, 2018, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2018-003533-15.

Hyperpolarized (HP) [1-13C]pyruvate cardiovascular magnetic resonance (CMR) imaging can visualize the uptake and intracellular conversion of [1-13C]pyruvate to either [1-13C]lactate or 13C-bicarbonate depending on the prevailing metabolic state. The aim of the present study was to combine an adenosine stress test with HP [1-13C]pyruvate CMR to detect cardiac metabolism in the healthy human heart at rest and during moderate stress. A prospective descriptive study was performed between October 2019 and August 2020. Healthy human subjects underwent cine CMR and HP [1-13C]pyruvate CMR at rest and during adenosine stress. HP [1-13C]pyruvate CMR images were acquired at the mid-left-ventricle (LV) level. Semi-quantitative assessment of first-pass myocardial [1-13C]pyruvate perfusion and metabolism were assessed. Paired t-tests were used to compare mean values at rest and during stress. Six healthy subjects (two female), age 29 ± 7 years were studied and no adverse reactions occurred. Myocardial [1-13C]pyruvate perfusion was significantly increased during stress with a reduction in time-to-peak from 6.2 ± 2.8 to 2.7 ± 1.3 s, p = 0.02. This higher perfusion was accompanied by an overall increased myocardial uptake and metabolism. The conversion rate constant (kPL) for lactate increased from 11 ± 9 *10–3 to 20 ± 10 * 10–3 s−1, p = 0.04. The pyruvate oxidation rate (kPB) increased from 4 ± 4 *10–3 to 12 ± 7 *10–3 s−1, p = 0.008. This increase in carbohydrate metabolism was positively correlated with heart rate (R2 = 0.44, p = 0.02). Adenosine stress testing combined with HP [1-13C]pyruvate CMR is feasible and well-tolerated in healthy subjects. We observed an increased pyruvate oxidation during cardiac stress. The present study is an important step in the translation of HP [1-13C]pyruvate CMR into clinical cardiac imaging. Trial registration EUDRACT, 2018-003533-15. Registered 4th of December 2018, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2018-003533-15

Aims The association between socioeconomic position and cardiovascular disease has not been well studied in patients with type 2 diabetes. We aimed to examine the association between socioeconomic position and first-time major adverse cardiovascular events (MACE) in patients with type 2 diabetes. Methods and results Through the Danish nationwide registers, we identified all residents with newly diagnosed type 2 diabetes between 2012 and 2017. Based on sex-stratified multivariable cause-specific Cox regression models, we calculated the standardized absolute 5-year risk of the composite outcome of first-time myocardial infarction, stroke, or cardiovascular mortality (MACE) according to income quartiles. A total of 57 106 patients with type 2 diabetes were included. During 155 989 person years, first-time MACE occurred in 2139 patients. Among both men and women, income was inversely associated with the standardized absolute 5-year risk of MACE. In men, the 5-year risk of MACE increased from 5.7% [95% confidence interval (CI) 4.9-6.5] in the highest income quartile to 9.3% (CI 8.3-10.2) in the lowest income group, with a risk difference of 3.5% (CI 2.4-4.7). In women, the risk of MACE increased from 4.2% (CI 3.4-5.0) to 6.1% (CI 5.2-7.0) according to income level, with a risk difference of 1.9% (CI 0.8-2.9). Conclusion Despite free access to medical care in Denmark, low-socioeconomic position was associated with a higher 5-year risk of first-time MACE in patients with incident type 2 diabetes. Our results suggest prevention strategies could be developed specifically for patients with low-socioeconomic position.

Abstract Background Hyperpolarized (HP) [1-13C]pyruvate cardiac magnetic resonance (CMR) imaging can visualize myocardial perfusion and metabolism beyound glucose uptake. Depending on the prevailing metabolic conditions, buid-up of either [1-13C]lactate or 13C-bicarbonate can be measured. The aim of the present study was to assess cardiac metabolism using HP [1-13C]pyruvate rest-stress CMR. Methods Six healthy volunteers underwent cine CMR and HP [1-13C]pyruvate CMR at rest and during an adenosine stress test. Signal from HP [1-13C]pyruvate and its downstream metabolites was measured at the mid-left-ventricle (LV) level. We did semi-quantitative assessment of first-pass myocardial [1-13C]pyruvate perfusion. Pressure-volume loops were assessed non-invasively. Results Myocardial [1-13C]pyruvate perfusion was significantly increased during stress with a reduction in time-to-peak from 6.2±2.8 sec to 2.7±1.3 sec, p=0.04. This higher perfusion was accompanied by an overall increased myocardial uptake and metabolism. The conversion rate constant (kPL) for lactate increased from 0.011±0.009 sec–1 to 0.020±0.010 sec–1, p=0.04. The pyruvate oxidation (kPB) increased from 0.004±0.004 sec–1 to 0.012±0.007 sec–1, p=0.008. This increase in oxidative metabolism was positively correlated with heart rate (R2=0.44, p=0.02). Conclusion We observed a significant increase in carbohydrate oxidation during cardiac stress in the healthy human heart. The present study forms the basis for comparisons in future research in patients with heart failure and coronary artery disease. HP [1-13C]pyruvate CMR could be a possible alternative to PET in the future. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Danish Heart FoundationIndependent Research Fund, Denmark Increased conversion rate of pyruvateIncreased metabolite signal in LV

BackgroundLow socioeconomic position may affect initiation of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucacon-like-peptide-1 receptor agonists (GLP-1RA) among patients with type 2 diabetes (T2D). We examined the association between socioeconomic position and initiation of SGLT-2i or GLP-1RA in patients with T2D at time of first intensification of antidiabetic treatment.MethodsThrough nationwide registers, we identified all Danish patients on metformin who initiated second-line add-on therapy between December 10, 2012, and December 31, 2020. For each time period (2012-2014, 2015-2017, and 2018-2020), we used multivariable multinomial logistic regression to associate disposable income, as proxy for socioeconomic position, with the probability of initiating a specific second-line treatment at time of first intensification. We reported probabilities standardised to the distribution of demographics and comorbidities of patients included in the last period (2018-2020).FindingsWe included 48915 patients (median age 62 years; 61·7% men). In each time period, high-income patients were more often men and had less comorbidities as compared with low income-patients. In each time period, the standardised probability of initiating a SGLT-2i or a GLP-1RA was significantly higher in the highest income group compared with the lowest: 11·4% vs. 9·5% (probability ratio [PR] 1·21, 95 % confidence interval [CI] 1·01-1·44) in 2012-2014; 22·6% vs. 19.6% (PR 1·15, CI 1·05-1·27) in 2015-2017; and 65·8% vs. 54·8% (PR 1·20, CI 1·16-1·24) in 2018-2020. The differences by income were consistent across multiple subgroups.InterpretationDespite a universal healthcare system, low socioeconomic position was consistently associated with a lower probability of initiating a SGLT-2i or a GLP-1RA. These disparities may widen the future socioeconomic gap in cardiovascular outcomes.FundingThe work was funded by unrestricted grants from ‘Region Sjaelland Den Sundhedsvidenskabelige Forskningsfond’ and ‘Murermester Lauritz Peter Christensen og hustru Kirsten Sigrid Christensens Fond’.

Abstract Background Social inequality poses a major public health challenge. Low socioeconomic position has been associated with cardiovascular disease in patients without diabetes. Yet, the association between socioeconomic position, type 2 diabetes, and first-time cardiovascular disease has not previously been investigated in a nationwide cohort from a country with equal access to healthcare. Purpose To examine the association between socioeconomic position and development of first-time major adverse cardiovascular events (MACE) in a Danish nationwide population of patients with incident type 2 diabetes. Methods Using the Danish nationwide registers, we identified all Danish residents with newly diagnosed type 2 diabetes between 2000 and 2017. Patients aged 40–79 years, without a history of ischemic heart disease and/or stroke were included. Income was used as a surrogate for socioeconomic position, and was assessed as quartiles of inflation adjusted, mean five-year income prior to index. Multivariable Cox proportional hazard analyses were used to assess the association between income and the primary composite outcome of ischemic stroke, acute myocardial infarction, and cardiovascular mortality (MACE). We assessed income as a time-dependent variable and adjusted for age, gender, calendar year, baseline comorbidities, and medication. Results In total 107,612 patients were included with a median age of 63 (interquartile range [IQR] 55–70) years and a median follow-up time of 6.8 (IQR 3.5–10.6) years. Patients in the lowest income quartile were older (median age 69 vs. 60 years) and more likely to be female (53.3% vs 36.7%) compared with the highest quartile (all P<0.0001). The 10-year risk of MACE decreased with higher income quartile: 30.3% (n=6814) in 1st quartile, 23.4% (n=4760) in 2nd quartile; 19.1% (n=3861) in 3rd quartile; 16.0% (n=3042) in 4th quartile (P<0.0001). In adjusted analysis, using the highest quartile as reference, the relative risk of MACE was inversely proportional to income (P-trend<0.0001): hazard ratio (HR) 1.59 (95% confidence interval [95% CI] 1.52–1.66) in 1st quartile; HR 1.42 (95% CI 1.36–1.49) in 2nd quartile; 1.20 (95% CI 1.14–1.25) in 3rd quartile. We found age specific differences in the risk of MACE between the younger (40–64 years) and the older (65–79 years) patients (P-interaction = 0.007). In stratified adjusted analysis, the youngest age group were associated with higher HR's compared to the oldest age group (Figure). The absolute unadjusted risk of MACE was highest in the elderly with low income. Conclusions Despite equal access to healthcare, low socioeconomic position was independently associated with an increased risk of first-time MACE in patients with incident type 2 diabetes. The finding was significant across age groups with the highest relative risks of MACE among younger patients. Our results indicate the importance of prevention strategies targeting patients with low socioeconomic position. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Zealand University Hospital Roskilde