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Abstract Metformin is an antihyperglycemic used to treat type 2 diabetes mellitus (T2DM). Patients with T2DM are at increased risk of cardiovascular disease. We explored the association between metformin use and cardiovascular magnetic resonance (CMR) derived stress myocardial blood flow (MBF), myocardial perfusion reserve (MPR) and major adverse cardiovascular events (MACE; all cause death, MI, stroke, heart failure hospitalisation and coronary revascularisation) in patients with T2DM. Multi-centre study of patients with T2DM, and healthy controls, underwent quantitative myocardial perfusion CMR using an artificial intelligence supported process. Multivariable regression analysis, and cox proportional hazard models of propensity score weighted patients quantified associations between metformin use, MBF, MPR, all cause death and MACE. Analysis included 572 patients with T2DM (68% prescribed metformin) with median follow-up 851 days (IQR 935 − 765). Metformin use was associated with an increase of MPR of 0.12 [0.08–0.40], p = 0.004. There were 82 MACE events (14.3%) including 25 (4.4%) deaths of which 16 were in those not prescribed metformin (8.7%), compared to 9 in patients prescribed metformin (2.3%): adjusted hazard ratio 0.24 (95% CI 0.08–0.70, p = 0.009). MACE events were similar between groups. This multicentre, inverse probability weighting propensity score analysis study showed that in patients with T2DM, metformin use is associated with higher MPR and improved all cause survival.

Abstract Background Pulmonary transit time (PTT) can be measured automatically from arterial input function (AIF) images of dual sequence first-pass perfusion imaging. PTT has been validated against invasive cardiac catheterisation correlating with both cardiac output and left ventricular filling pressure (both important prognostic markers in heart failure). We hypothesized that prolonged PTT is associated with clinical outcomes in patients with heart failure. Methods We recruited outpatients with a recent diagnosis of non-ischaemic heart failure with left ventricular ejection fraction (LVEF)

Abstract Background When feasible, guidelines recommend mitral valve repair (MVr) over mitral valve replacement (MVR) to treat primary mitral regurgitation (MR), based upon historic outcome studies and transthoracic echocardiography (TTE) reverse remodeling studies. Cardiovascular magnetic resonance (CMR) offers reference standard biventricular assessment with superior MR quantification compared to TTE. Using serial CMR in primary MR patients, we aimed to investigate cardiac reverse remodeling and residual MR post-MVr vs MVR with chordal preservation. Methods 83 patients with ≥ moderate-severe MR on TTE were prospectively recruited. 6-min walk tests (6MWT) and CMR imaging including cine imaging, aortic/pulmonary through-plane phase contrast imaging, T1 maps and late-gadolinium-enhanced (LGE) imaging were performed at baseline and 6 months after mitral surgery or watchful waiting (control group). Results 72 patients completed follow-up (Controls = 20, MVr = 30 and MVR = 22). Surgical groups demonstrated comparable baseline cardiac indices and co-morbidities. At 6-months, MVr and MVR groups demonstrated comparable improvements in 6MWT distances (+ 57 ± 54 m vs + 64 ± 76 m respectively, p = 1), reduced indexed left ventricular end-diastolic volumes (LVEDVi; − 29 ± 21 ml/m2 vs − 37 ± 22 ml/m2 respectively, p = 0.584) and left atrial volumes (− 23 ± 30 ml/m2 and − 39 ± 26 ml/m2 respectively, p = 0.545). At 6-months, compared with controls, right ventricular ejection fraction was poorer post-MVr (47 ± 6.1% vs 53 ± 8.0% respectively, p = 0.01) compared to post-MVR (50 ± 5.7% vs 53 ± 8.0% respectively, p = 0.698). MVR resulted in lower residual MR-regurgitant fraction (RF) than MVr (12 ± 8.0% vs 21 ± 11% respectively, p = 0.022). Baseline and follow-up indices of diffuse and focal myocardial fibrosis (Native T1 relaxation times, extra-cellular volume and quantified LGE respectively) were comparable between groups. Stepwise multiple linear regression of indexed variables in the surgical groups demonstrated baseline indexed mitral regurgitant volume as the sole multivariate predictor of left ventricular (LV) end-diastolic reverse remodelling, baseline LVEDVi as the most significant independent multivariate predictor of follow-up LVEDVi, baseline indexed LV end-systolic volume as the sole multivariate predictor of follow-up LV ejection fraction and undergoing MVR (vs MVr) as the most significant (p

ABSTRACT: Background: Patients with diabetes mellitus (DM) and heart failure (HF) have worse outcomes than normoglycemic HF patients. Cardiovascular magnetic resonance (CMR) can identify ischemic heart disease (IHD) and quantify coronary microvascular dysfunction (CMD) using myocardial perfusion reserve (MPR). We aimed to quantify the extent of silent IHD and CMD in patients with DM presenting with HF. Methods: Prospectively recruited outpatients undergoing assessment into the etiology of HF underwent in-line quantitative perfusion CMR for calculation of stress and rest myocardial blood flow (MBF) and MPR. Exclusions included angina or history of IHD. Patients were followed up (median 3.0 years) for major adverse cardiovascular events (MACE). Results: Final analysis included 343 patients (176 normoglycemic, 84 with pre-diabetes, and 83 with DM). Prevalence of silent IHD was highest in DM 31% ( 26/83), then pre-diabetes 20% (17/84) then normoglycemia 17%, ( 30/176). Stress MBF was lowest in DM (1.53 ± 0.52), then pre-diabetes (1.59 ± 0.54) then normoglycemia (1.83 ± 0.62). MPR was lowest in DM (2.37 ± 0.85) then pre-diabetes (2.41 ± 0.88) then normoglycemia (2.61 ± 0.90). During follow-up, 45 patients experienced at least one MACE. On univariate Cox regression analysis, MPR and presence of silent IHD were both associated with MACE. However, after correction for HbA1c, age, and left ventricular ejection fraction, the associations were no longer significant. Conclusion: Patients with DM and HF had higher prevalence of silent IHD, more evidence of CMD, and worse cardiovascular outcomes than their non-diabetic counterparts. These findings highlight the potential value of CMR for the assessment of silent IHD and CMD in patients with DM presenting with HF.

Abstract Background The underlying pathophysiology of post-coronavirus disease 2019 (long-COVID-19) syndrome remains unknown, but increased cardiometabolic demand and state of mitochondrial dysfunction have emerged as candidate mechanisms. Cardiovascular magnetic resonance (CMR) provides insight into pathophysiological mechanisms underlying cardiovascular disease and 31-phosphorus CMR spectroscopy (31P-CMRS) allows non-invasive assessment of the myocardial energetic state. The main aim of the study was to assess whether long COVID-19 syndrome is associated with abnormalities of myocardial structure, function, perfusion and energy metabolism. Methods Prospective case–control study. A total of 20 patients with a clinical diagnosis of long COVID-19 syndrome (seropositive) and no prior underlying cardiovascular disease (CVD) and 10 matching healthy controls underwent 31P-CMRS and CMR at 3T at a single time point. All patients had been symptomatic with acute COVID-19, but none required hospital admission. Results Between the long COVID-19 syndrome patients and matched contemporary healthy controls there were no differences in myocardial energetics (phosphocreatine to ATP ratio), in cardiac structure (biventricular volumes), function (biventricular ejection fractions, global longitudinal strain), tissue characterization (T1 mapping and late gadolinium enhancement) or perfusion (myocardial rest and stress blood flow, myocardial perfusion reserve). One patient with long COVID-19 syndrome showed subepicardial hyperenhancement on late gadolinium enhancement imaging compatible with prior myocarditis, but no accompanying abnormality in cardiac size, function, perfusion, extracellular volume fraction, native T1, T2 or cardiac energetics. Conclusions In this prospective case–control study, the overwhelming majority of patients with a clinical long COVID-19 syndrome with no prior CVD did not exhibit any abnormalities in myocardial energetics, structure, function, blood flow or tissue characteristics.

Background. Ischaemia with nonobstructive coronary arteries is most commonly caused by coronary microvascular dysfunction but remains difficult to diagnose without invasive testing. Myocardial blood flow (MBF) can be quantified noninvasively on stress perfusion cardiac magnetic resonance (CMR) or positron emission tomography but neither is routinely used in clinical practice due to practical and technical constraints. Quantification of coronary sinus (CS) flow may represent a simpler method for CMR MBF quantification. 4D flow CMR offers comprehensive intracardiac and transvalvular flow quantification. However, it is feasibility to quantify MBF remains unknown. Methods. Patients with acute myocardial infarction (MI) and healthy volunteers underwent CMR. The CS contours were traced from the 2-chamber view. A reformatted phase contrast plane was generated through the CS, and flow was quantified using 4D flow CMR over the cardiac cycle and normalised for myocardial mass. MBF and resistance (MyoR) was determined in ten healthy volunteers, ten patients with myocardial infarction (MI) without microvascular obstruction (MVO), and ten with known MVO. Results. MBF was quantified in all 30 subjects. MBF was highest in healthy controls (123.8 ± 48.4 mL/min), significantly lower in those with MI (85.7 ± 30.5 mL/min), and even lower in those with MI and MVO (67.9 ± 29.2 mL/min/) (P

Abstract The role of inflammation in cardiovascular pathophysiology has gained a lot of research interest in recent years. Cardiovascular Magnetic Resonance has been a powerful tool in the non-invasive assessment of inflammation in several conditions. More recently, Ultrasmall superparamagnetic particles of iron oxide have been successfully used to evaluate macrophage activity and subsequently inflammation on a cellular level. Current evidence from research studies provides encouraging data and confirms that this evolving method can potentially have a huge impact on clinical practice as it can be used in the diagnosis and management of very common conditions such as coronary artery disease, ischaemic and non-ischaemic cardiomyopathy, myocarditis and atherosclerosis. Another important emerging concept is that of myocardial energetics. With the use of phosphorus magnetic resonance spectroscopy, myocardial energetic compromise has been proved to be an important feature in the pathophysiological process of several conditions including diabetic cardiomyopathy, inherited cardiomyopathies, valvular heart disease and cardiac transplant rejection. This unique tool is therefore being utilized to assess metabolic alterations in a wide range of cardiovascular diseases. This review systematically examines these state-of-the-art methods in detail and provides an insight into the mechanisms of action and the clinical implications of their use.

Objectives. In a cohort of type 2 diabetic (T2D) patients who underwent baseline cardiac magnetic resonance (CMR) and biomarker testing, during a median follow-up of 6 years, we aimed to determine longitudinal changes in the phenotypic expression of heart disease in diabetes, report clinical outcomes, and compare baseline clinical characteristics and CMR findings of patients who experienced major adverse cardiovascular events (MACE) to those remaining MACE free. Background. T2D increases the risk of heart failure (HF) and cardiovascular mortality. The long-term impact of T2D on cardiac phenotype in the absence of cardiovascular disease and other clinical events is unknown. Methods. Patients with T2D (n = 100) with no history of cardiovascular disease or hypertension were recruited at baseline. Biventricular volumes, function, and myocardial extracellular volume fraction (ECV) were assessed by CMR, and blood biomarkers were taken. Follow-up CMR was repeated in those without interim clinical events after 6 years. Results. Follow-up was successful in 83 participants. Of those, 29 experienced cardiovascular/clinical events (36%). Of the remaining 59, 32 patients who experienced no events received follow-up CMR. In this cohort, despite no significant changes in blood pressure, weight, or glycated hemoglobin, significant reductions in biventricular end-diastolic volumes and ejection fractions occurred over time. The mean ECV was unchanged. Baseline plasma high-sensitivity cardiac troponin T (hs-cTnT) was significantly associated with a change in left ventricular (LV) ejection fraction. Patients who experienced MACE had higher LV mass and greater LV concentricity than those who remained event free. Conclusions. T2D results in reductions in biventricular size and systolic function over time even in the absence of cardiovascular/clinical events.

Cardiovascular magnetic resonance (CMR) imaging is a versatile tool that has established itself as the reference method for functional assessment and tissue characterisation. CMR helps to diagnose, monitor disease course and sub-phenotype disease states. Several emerging CMR methods have the potential to offer a personalised medicine approach to treatment. CMR tissue characterisation is used to assess myocardial oedema, inflammation or thrombus in various disease conditions. CMR derived scar maps have the potential to inform ablation therapy—both in atrial and ventricular arrhythmias. Quantitative CMR is pushing boundaries with motion corrections in tissue characterisation and first-pass perfusion. Advanced tissue characterisation by imaging the myocardial fibre orientation using diffusion tensor imaging (DTI), has also demonstrated novel insights in patients with cardiomyopathies. Enhanced flow assessment using four-dimensional flow (4D flow) CMR, where time is the fourth dimension, allows quantification of transvalvular flow to a high degree of accuracy for all four-valves within the same cardiac cycle. This review discusses these emerging methods and others in detail and gives the reader a foresight of how CMR will evolve into a powerful clinical tool in offering a precision medicine approach to treatment, diagnosis, and detection of disease.

Background: Type 2 diabetes (T2D) is associated with an increased risk of heart failure (HF) and cardiovascular mortality. A large-scale meta-analysis on HF found that diabetes was more frequent in women than men, and diabetes appeared to have attenuated the otherwise protective effect of female sex on progression of cardiomyopathy. The exact underlying mechanisms for this remain unclear. Here, we aimed to determine the effect of sex on the phenotypic expression of diabetic heart disease in patients with T2D. Methods: A total of 62 male [mean age 44 ± 8 years, body mass index (BMI) 33 ± 5 kg/m 2 , mean HBA1c of 7.8 ± 1.8%] and 67 female (44 ± 10 years, BMI 35 ± 6 kg/m 2 , HBA1c 7.6 ± 1.2%) T2D patients on oral glucose-lowering treatment, and 16 male (48 ± 17 years, BMI 25 ± 3 kg/m 2 ) and 14 female (50 ± 10 years, BMI 25 ± 4 kg/m 2 ) controls were recruited. Left ventricular (LV) volumes, mass, function and deformation, and left atrial (LA) volumes and function were assessed using cardiac magnetic resonance imaging (CMR). Results: Participants in all groups were of similar age, and there were no significant differences in blood pressure (BP), diabetes duration or metabolic profile between the two diabetes groups. Concentric remodeling was present in both sexes ( p

Cardiac calcified amorphous tumours of the heart are rare non-neoplastic cardiac masses that can present like a malignant mass or an intra-cardiac thrombus. We report an extremely unusual case of a 73 year old man who presented to hospital with dyspnoea and subsequent investigations revealed multiple cardiac CATs.

Background: Pulmonary transit time (PTT) can be measured automatically from arterial input function (AIF) images of dual sequence first-pass perfusion imaging. PTT has been validated against invasive cardiac catheterisation correlating with both cardiac output and left ventricular filling pressure (both important prognostic markers in heart failure). We hypothesized that prolonged PTT is associated with clinical outcomes in patients with heart failure. Methods: We recruited outpatients with a recent diagnosis of non-ischaemic heart failure with left ventricular ejection fraction (LVEF) < 50% on referral echocardiogram. Patients were followed up by a review of medical records for major adverse cardiovascular events (MACE) defined as all-cause mortality, heart failure hospitalization, ventricular arrhythmia, stroke or myocardial infarction. PTT was measured automatically from low-resolution AIF dynamic series of both the LV and RV during rest perfusion imaging, and the PTT was measured as the time (in seconds) between the centroid of the left (LV) and right ventricle (RV) indicator dilution curves. Results: Patients (N = 294) were followed-up for median 2.0 years during which 37 patients (12.6%) had at least one MACE event. On univariate Cox regression analysis there was a significant association between PTT and MACE (Hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.08–1.25, P = 0.0001). There was also significant association between PTT and heart failure hospitalisation (HR 1.15, 95% CI 1.02–1.29, P = 0.02) and moderate correlation between PTT and N-terminal pro B-type natriuretic peptide (NT-proBNP, r = 0.51, P < 0.001). PTT remained predictive of MACE after adjustment for clinical and imaging factors but was no longer significant once adjusted for NT-proBNP. Conclusions: PTT measured automatically during CMR perfusion imaging in patients with recent onset non-ischaemic heart failure is predictive of MACE and in particular heart failure hospitalisation. PTT derived in this way may be a non-invasive marker of haemodynamic congestion in heart failure and future studies are required to establish if prolonged PTT identifies those who may warrant closer follow-up or medicine optimisation to reduce the risk of future adverse events. [ABSTRACT FROM AUTHOR]

Primary outcome was pregnancy loss (miscarriage, neonatal death, termination, stillbirth), secondary outcomes included pregnancy prolongation, preterm birth, and maternal and neonatal outcomes. 24 Reducing inequalities in preterm birth and stillbirth through personalised risk-assessment an... Jenny Carter 1; Jane Sandall 1; Tommy's National Centre for Maternity Improvement 2 1 King's College London, London, UK; 2 Royal College of Obstetricians and Gynaecologists, Lon... B Abstract b B Background: b The Tommy's App (a web-based, CE-marked medical device) assesses risk of placental dysfunction and preterm birth much more accurately than current methods, and instantly recommends personalised evidenced-based care pathways. The model included mothers age, height, parity, smoking status, ethnicity, and any history of hypertension, pre-eclampsia, previous stillbirth or SGA baby, and gestational age at delivery. Longitudinal maternal cardiac adaptation in hypertensive disorders of pregnancy Hua Zen Ling; Gavin Guy; Kypros H. Nicolaides; Nikos A. Kametas Fetal Medicine Research Institute, King's College London, London, UK B Abstract b Preeclampsia (PE), compared to gestational hypertension (GH) has traditionally been considered the most severe hypertensive disorders in pregnancy, with worse outcomes and future cardiovascular morbidities. The model included mothers age, height, weight, mode of conception, parity, smoking status, ethnicity, and any history of diabetes, hypertension, pre-eclampsia, previous stillbirth or SGA baby, and gestational age at delivery. [Extracted from the article]

Aims Recently developed in-line automated cardiovascular magnetic resonance (CMR) myocardial perfusion mapping has been shown to be reproducible and comparable with positron emission tomography (PET), and can be easily integrated into clinical workflows. Bringing quantitative myocardial perfusion CMR into routine clinical care requires knowledge of sex- and age-specific normal values in order to define thresholds for disease detection. This study aimed to establish sex- and age-specific normal values for stress and rest CMR myocardial blood flow (MBF) in healthy volunteers. Methods and results A total of 151 healthy volunteers recruited from two centres underwent adenosine stress and rest myocardial perfusion CMR. In-line automatic reconstruction and post processing of perfusion data were implemented within the Gadgetron software framework, creating pixel-wise perfusion maps. Rest and stress MBF were measured, deriving myocardial perfusion reserve (MPR) and were subdivided by sex and age. Mean MBF in all subjects was 0.62 ± 0.13 mL/g/min at rest and 2.24 ± 0.53 mL/g/min during stress. Mean MPR was 3.74 ± 1.00. Compared with males, females had higher rest (0.69 ± 0.13 vs. 0.58 ± 0.12 mL/g/min, P < 0.01) and stress MBF (2.41 ± 0.47 vs. 2.13 ± 0.54 mL/g/min, P = 0.001). Stress MBF and MPR showed significant negative correlations with increasing age (r = −0.43, P < 0.001 and r = −0.34, P < 0.001, respectively). Conclusion Fully automated in-line CMR myocardial perfusion mapping produces similar normal values to the published CMR and PET literature. There is a significant increase in rest and stress MBF, but not MPR, in females and a reduction of stress MBF and MPR with advancing age, advocating the use of sex- and age-specific reference ranges for diagnostic use. [ABSTRACT FROM AUTHOR]

Background. Ischaemia with nonobstructive coronary arteries is most commonly caused by coronary microvascular dysfunction but remains difficult to diagnose without invasive testing. Myocardial blood flow (MBF) can be quantified noninvasively on stress perfusion cardiac magnetic resonance (CMR) or positron emission tomography but neither is routinely used in clinical practice due to practical and technical constraints. Quantification of coronary sinus (CS) flow may represent a simpler method for CMR MBF quantification. 4D flow CMR offers comprehensive intracardiac and transvalvular flow quantification. However, it is feasibility to quantify MBF remains unknown. Methods. Patients with acute myocardial infarction (MI) and healthy volunteers underwent CMR. The CS contours were traced from the 2-chamber view. A reformatted phase contrast plane was generated through the CS, and flow was quantified using 4D flow CMR over the cardiac cycle and normalised for myocardial mass. MBF and resistance (MyoR) was determined in ten healthy volunteers, ten patients with myocardial infarction (MI) without microvascular obstruction (MVO), and ten with known MVO. Results. MBF was quantified in all 30 subjects. MBF was highest in healthy controls (123.8 ± 48.4 mL/min), significantly lower in those with MI (85.7 ± 30.5 mL/min), and even lower in those with MI and MVO (67.9 ± 29.2 mL/min/) (P < 0.01 for both differences). Compared with healthy controls, MyoR was higher in those with MI and even higher in those with MI and MVO (0.79 (±0.35) versus 1.10 (±0.50) versus 1.50 (±0.69), P = 0.02). Conclusions. MBF and MyoR can be quantified from 4D flow CMR. Resting MBF was reduced in patients with MI and MVO. [ABSTRACT FROM AUTHOR]

Aims The 2016 European Society of Cardiology Heart Failure Guidelines defined a new category: heart failure with mid-range ejection fraction (HFmrEF) of 40–49%. This new category was highlighted as having limited evidence and research was advocated into underlying characteristics, pathophysiology, and diagnosis. We used multi-parametric cardiovascular magnetic resonance (CMR) to define the cardiac phenotype of presumed non-ischaemic HFmrEF. Methods and results Patients (N = 300, 62.7 ± 13 years, 63% males) with a clinical diagnosis of heart failure with no angina symptoms, history of myocardial infarction, or coronary intervention were prospectively recruited. Patients underwent clinical assessment and CMR including T1 mapping, extracellular volume (ECV) mapping, late gadolinium enhancement, and measurement of myocardial blood flow at rest and maximal hyperaemia. Of 273 patients in the final analysis, 93 (34%) patients were categorized as HFmrEF, 46 (17%) as heart failure with preserved ejection fraction (HFpEF), and 134 (49%) as heart failure with reduced ejection fraction (HFrEF). Nineteen (20%) patients with HFmrEF had evidence of occult ischaemic heart disease. Diffuse fibrosis and hyperaemic myocardial blood flow were similar in HFmrEF and HFpEF, but HFmrEF showed significantly lower native T1 (1311 ± 32 vs. 1340 ± 45 ms, P < 0.001), ECV (24.6 ± 3.2 vs. 26.3 ± 3.1%, P < 0.001), and higher myocardial perfusion reserve (2.75 ± 0.84 vs. 2.28 ± 0.84, P < 0.001) compared with HFrEF. Conclusion Patients with HFmrEF share most phenotypic characteristics with HFpEF, including the degree of microvascular impairment and fibrosis, but have a high prevalence of occult ischaemic heart disease similar to HFrEF. Further work is needed to confirm how the phenotype of HFmrEF responds to medical therapy. [ABSTRACT FROM AUTHOR]

Objective: We investigated if women with gestational diabetes mellitus (GDM) in the third trimester of pregnancy exhibit adverse cardiac alterations in myocardial energetics, function, or tissue characteristics.Research Design and Methods: Thirty-eight healthy, pregnant women and 30 women with GDM were recruited. Participants underwent phosphorus MRS and cardiovascular magnetic resonance for assessment of myocardial energetics (phosphocreatine [PCr] to ATP ratio), tissue characteristics, biventricular volumes and ejection fractions, left ventricular (LV) mass, global longitudinal shortening (GLS), and mitral in-flow E-wave to A-wave ratio.Results: Participants were matched for age, gestational age, and ethnicity. The following data are reported as mean ± SD. The women with GDM had higher BMI (27 ± 4 vs. 33 ± 5 kg/m2; P = 0.0001) and systolic (115 ± 11 vs. 121 ± 13 mmHg; P = 0.04) and diastolic (72 ± 7 vs. 76 ± 9 mmHg; P = 0.04) blood pressures. There was no difference in N-terminal pro-brain natriuretic peptide concentrations between the groups. The women with GDM had lower myocardial PCr to ATP ratio (2.2 ± 0.3 vs. 1.9 ± 0.4; P < 0.0001), accompanied by lower LV end-diastolic volumes (76 ± 12 vs. 67 ± 11 mL/m2; P = 0.002) and higher LV mass (90 ± 13 vs. 103 ± 18 g; P = 0.001). Although ventricular ejection fractions were similar, the GLS was reduced in women with GDM (-20% ± 3% vs. -18% ± 3%; P = 0.008).Conclusions: Despite no prior diagnosis of diabetes, women with obesity and GDM manifest impaired myocardial contractility and higher LV mass, associated with reductions in myocardial energetics in late pregnancy compared with lean women with healthy pregnancy. These findings may aid our understanding of the long-term cardiovascular risks associated with GDM. [ABSTRACT FROM AUTHOR]

Objective: Type 2 diabetes mellitus (T2DM) is associated with worsened clinical outcomes in hypertrophic cardiomyopathy (HCM) patients. We sought to investigate whether HCM patients with T2DM comorbidity exhibit adverse cardiac alterations in myocardial energetics, function, perfusion, or tissue characteristics.Research Design and Methods: A total of 55 participants with concomitant HCM and T2DM (HCM-DM) (n = 20) or isolated HCM (n = 20) and healthy volunteers (HV) (n = 15) underwent 31P-MRS and cardiovascular MRI. The HCM groups were matched for HCM phenotype.Results: Mean ± SD European Society of Cardiology sudden cardiac death risk scores were comparable between the HCM groups (HCM 2.2 ± 1.5%, HCM-DM 1.9 ± 1.2%; P = not significant), and sarcomeric mutations were equally common. HCM-DM patients had the highest median NT-proBNP levels (HV 42 ng/L [interquartile range 35-66], HCM 298 ng/L [157-837], HCM-DM 726 ng/L [213-8,695]; P < 0.0001). Left ventricular (LV) ejection fraction, mass, and wall thickness were similar between the HCM groups. HCM-DM patients displayed a greater degree of fibrosis burden with higher scar percentage and lower global longitudinal strain compared with HCM patients. PCr/ATP (the relative concentrations of phosphocreatine and ATP) was significantly lower in the HCM-DM group than in both HCM and HV (HV 2.17 ± 0.49, HCM 1.93 ± 0.38, HCM-DM 1.54 ± 0.27; P = 0.002). In a similar pattern, stress myocardial blood flow was significantly lower in the HCM-DM group than in both HCM and HV (HV 2.06 ± 0.42 mL/min/g, HCM 1.74 ± 0.44 mL/min/g, HCM-DM 1.39 ± 0.42 mL/min/g; P = 0.002).Conclusions: We show for the first time that HCM-DM patients display greater reductions in myocardial energetics, perfusion, and contractile function and higher myocardial scar burden and serum NT-proBNP levels compared with patients with isolated HCM despite similar LV mass and wall thickness and presence of sarcomeric mutations. These adverse phenotypic features may be important components of the adverse clinical manifestation attributable to a combined presence of HCM and T2DM. [ABSTRACT FROM AUTHOR]

Background Using serial imaging over time, this case reviews the natural history of co-morbid Type two diabetes (T2D) and apical hypertrophic cardiomyopathy (HCM) and assesses the potential combined impact on myocardial structure and perfusion. Case summary A 59-year-old patient with concomitant T2D and an apical phenotype of HCM was seen over a 11-year period with a significant burden of anginal chest pain. Chest pain was refractory to anti-anginal medical therapy and persisted at on-going follow-up. Multi-modality imaging demonstrated significant deterioration in coronary microvascular function and increased myocardial scar burden despite unobstructed epicardial coronary arteries. Discussion Comorbidity with T2D and apical HCM resulted in a significant increase in myocardial fibrosis and deterioration in coronary microvascular function. [ABSTRACT FROM AUTHOR]

Objective: This study sought to assess whether diabetes affects coronary microvascular function in individuals with normal body weight. Methods: Seventy‐five participants (30 patients with type 2 diabetes [T2D] who were overweight [O‐T2D], 15 patients with T2D who were lean [LnT2D], 15 healthy volunteers who were lean [LnHV], and 15 healthy volunteers who were overweight [O‐HV]) without established cardiovascular disease were recruited. Participants underwent magnetic resonance imaging for assessment of subcutaneous, epicardial, and visceral adipose tissue areas, adenosine stress myocardial blood flow (MBF), and cardiac structure and function. Results: Stress MBF was reduced only in the O‐T2D group (mean [SD], LnHV = 2.07 [0.47] mL/g/min, O‐HV = 2.08 [0.42] mL/g/min, LnT2D = 2.16 [0.36] mL/g/min, O‐T2D = 1.60 [0.28] mL/g/min; p ≤ 0.0001). Accumulation of visceral fat was evident in the LnT2D group at similar levels to the O‐HV group (LnHV = 127 [53] cm2, O‐HV = 181 [60] cm2, LnT2D = 182 [99] cm2, O‐T2D = 288 [72] cm2; p < 0.0001). Only the O‐T2D group showed reductions in left ventricular ejection fraction (LnHV = 63% [4%], O‐HV = 63% [4%], LnT2D = 60% [5%], O‐T2D = 58% [6%]; p = 0.0008) and global longitudinal strain (LnHV = −15.1% [3.1%], O‐HV= −15.2% [3.7%], LnT2D = −13.4% [2.7%], O‐T2D = −11.1% [2.8%]; p = 0.002) compared with both control groups. Conclusions: Patients with T2D and normal body weight do not show alterations in global stress MBF, but they do show significant increases in visceral adiposity. Patients with T2D who were overweight and had no prior cardiovascular disease showed an increase in visceral adiposity and significant reductions in stress MBF. [ABSTRACT FROM AUTHOR]

Aims Microvascular dysfunction in hypertrophic cardiomyopathy (HCM) is predictive of clinical decline, however underlying mechanisms remain unclear. Cardiac diffusion tensor imaging (cDTI) allows in vivo characterization of myocardial microstructure by quantifying mean diffusivity (MD), fractional anisotropy (FA) of diffusion, and secondary eigenvector angle (E2A). In this cardiac magnetic resonance (CMR) study, we examine associations between perfusion and cDTI parameters to understand the sequence of pathophysiology and the interrelation between vascular function and underlying microstructure. Methods and results Twenty HCM patients underwent 3.0T CMR which included: spin-echo cDTI, adenosine stress and rest perfusion mapping, cine-imaging, and late gadolinium enhancement (LGE). Ten controls underwent cDTI. Myocardial perfusion reserve (MPR), MD, FA, E2A, and wall thickness were calculated per segment and further divided into subendocardial (inner 50%) and subepicardial (outer 50%) regions. Segments with wall thickness ≤11 mm, MPR ≥2.2, and no visual LGE were classified as 'normal'. Compared to controls, 'normal' HCM segments had increased MD (1.61 ± 0.09 vs. 1.46 ± 0.07 × 10−3 mm2/s, P  = 0.02), increased E2A (60 ± 9° vs. 38 ± 12°, P  < 0.001), and decreased FA (0.29 ± 0.04 vs. 0.35 ± 0.02, P  = 0.002). Across all HCM segments, subendocardial regions had higher MD and lower MPR than subepicardial (MDendo 1.61 ± 0.08 × 10−3 mm2/s vs. MDepi 1.56 ± 0.18 × 10−3 mm2/s, P  = 0.003, MPRendo 1.85 ± 0.83, MPRepi 2.28 ± 0.87, P  < 0.0001). Conclusion In HCM patients, even in segments with normal wall thickness, normal perfusion, and no scar, diffusion is more isotropic than in controls, suggesting the presence of underlying cardiomyocyte disarray. Increased E2A suggests the myocardial sheetlets adopt hypercontracted angulation in systole. Increased MD, most notably in the subendocardium, is suggestive of regional remodelling which may explain the reduced subendocardial blood flow. [ABSTRACT FROM AUTHOR]

The article discusses Coronary micro vascular dysfunction and compromised cardiac energy production have been proposed as pivotal features underpinning diabetic cardiomyopathy. Topics include the relative associations of impaired cardiac energetics and perfusion to systolic and diastolic subclinical functional changes at rest and in response to acute hemodynamic stress in T2D have not been reported.

Objectives. In a cohort of type 2 diabetic (T2D) patients who underwent baseline cardiac magnetic resonance (CMR) and biomarker testing, during a median follow-up of 6 years, we aimed to determine longitudinal changes in the phenotypic expression of heart disease in diabetes, report clinical outcomes, and compare baseline clinical characteristics and CMR findings of patients who experienced major adverse cardiovascular events (MACE) to those remaining MACE free. Background. T2D increases the risk of heart failure (HF) and cardiovascular mortality. The long-term impact of T2D on cardiac phenotype in the absence of cardiovascular disease and other clinical events is unknown. Methods. Patients with T2D (n = 100) with no history of cardiovascular disease or hypertension were recruited at baseline. Biventricular volumes, function, and myocardial extracellular volume fraction (ECV) were assessed by CMR, and blood biomarkers were taken. Follow-up CMR was repeated in those without interim clinical events after 6 years. Results. Follow-up was successful in 83 participants. Of those, 29 experienced cardiovascular/clinical events (36%). Of the remaining 59, 32 patients who experienced no events received follow-up CMR. In this cohort, despite no significant changes in blood pressure, weight, or glycated hemoglobin, significant reductions in biventricular end-diastolic volumes and ejection fractions occurred over time. The mean ECV was unchanged. Baseline plasma high-sensitivity cardiac troponin T (hs-cTnT) was significantly associated with a change in left ventricular (LV) ejection fraction. Patients who experienced MACE had higher LV mass and greater LV concentricity than those who remained event free. Conclusions. T2D results in reductions in biventricular size and systolic function over time even in the absence of cardiovascular/clinical events. [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of major adverse cardiovascular (CV) events and hospitalization for heart failure (HF) in patients with type 2 diabetes (T2D). Using CV MRI (CMR) and 31P-MRS in a longitudinal cohort study, we aimed to investigate the effects of the selective SGLT2 inhibitor empagliflozin on myocardial energetics and cellular volume, function, and perfusion. Eighteen patients with T2D underwent CMR and 31P-MRS scans before and after 12 weeks' empagliflozin treatment. Plasma N-terminal prohormone B-type natriuretic peptide (NT-proBNP) levels were measured. Ten volunteers with normal glycemic control underwent an identical scan protocol at a single visit. Empagliflozin treatment was associated with significant improvements in phosphocreatine-to-ATP ratio (1.52 to 1.76, P = 0.009). This was accompanied by a 7% absolute increase in the mean left ventricular ejection fraction (P = 0.001), 3% absolute increase in the mean global longitudinal strain (P = 0.01), 8 mL/m2 absolute reduction in the mean myocardial cell volume (P = 0.04), and 61% relative reduction in the mean NT-proBNP (P = 0.05) from baseline measurements. No significant change in myocardial blood flow or diastolic strain was detected. Empagliflozin thus ameliorates the "cardiac energy-deficient" state, regresses adverse myocardial cellular remodeling, and improves cardiac function, offering therapeutic opportunities to prevent or modulate HF in T2D. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes (T2D) is associated with an increased risk of cardiovascular (CV) disease. In patients with T2D and established CV disease, selective inhibitors of sodium–glucose cotransporter 2 (SGLT2) have been shown to decrease CV and all-cause mortality, and heart failure (HF) admissions. Utilising CV magnetic resonance imaging (CMR) and continuous glucose monitoring (CGM) by FreeStyle Libre Pro Sensor, we aim to explore the mechanisms of action which give Empagliflozin, an SGLT2 inhibitor, its beneficial CV effects and compare these to the effects of dipeptidyl peptidase-4 inhibitor Sitagliptin. Methods: This is a single centre, open-label, cross-over trial conducted at the Leeds Teaching Hospitals NHS Trust. Participants are randomised for the order of treatment and receive 3 months therapy with Empagliflozin, and 3 months therapy with Sitagliptin sequentially. Twenty-eight eligible T2D patients with established ischaemic heart disease will be recruited. Patients undergo serial CMR scans on three visits. Discussion: The primary outcome measure is the myocardial perfusion reserve in remote myocardium. We hypothesise that Empaglifozin treatment is associated with improvements in myocardial blood flow and reductions in myocardial interstitial fibrosis, independent of CGM measured glycemic control in patients with T2D and established CV disease. Trial registration: This study has full research ethics committee approval (REC: 18/YH/0190) and data collection is anticipated to finish in December 2021. This study was retrospectively registered at https://doi.org/10.1186/ISRCTN82391603 and monitored by the University of Leeds. The study results will be submitted for publication within 6 months of completion. [ABSTRACT FROM AUTHOR]

Purpose: Exercise cardiovascular magnetic resonance (Ex-CMR) typically requires complex post-processing or transient exercise cessation, decreasing clinical utility. We aimed to demonstrate the feasibility of assessing biventricular volumes and great vessel flow during continuous in-scanner Ex-CMR, using vendor provided Compressed SENSE (C-SENSE) sequences and commercial analysis software (Cvi42). Methods: 12 healthy volunteers (8-male, age: 35 ± 9 years) underwent continuous supine cycle ergometer (Lode-BV) Ex-CMR (1.5T Philips, Ingenia). Free-breathing, respiratory navigated C-SENSE short-axis cines and aortic/pulmonary phase contrast magnetic resonance (PCMR) sequences were validated against clinical sequences at rest and used during low and moderate intensity Ex-CMR. Optimal PCMR C-SENSE acceleration, C-SENSE-3 (CS3) vs C-SENSE-6 (CS6), was further investigated by image quality scoring. Intra-and inter-operator reproducibility of biventricular and flow indices was performed. Results: All CS3 PCMR image quality scores were superior (p < 0.05) to CS6 sequences, except pulmonary PCMR at moderate exercise. Resting stroke volumes from clinical PCMR sequences correlated stronger with CS3 than CS6 sequences. Resting biventricular volumes from CS3 and clinical sequences correlated very strongly (r > 0.93). During Ex-CMR, biventricular end-diastolic volumes (EDV) remained unchanged, except right-ventricular EDV decreasing at moderate exercise. Biventricular ejection-fractions increased at each stage. Exercise biventricular cine and PCMR stroke volumes correlated very strongly (r ≥ 0.9), demonstrating internal validity. Intra-observer reproducibility was excellent, co-efficient of variance (COV) < 10%. Inter-observer reproducibility was excellent, except for resting right-ventricular, and exercise bi-ventricular end-systolic volumes which were good (COV 10–20%). Conclusion: Biventricular function, aortic and pulmonary flow assessment during continuous Ex-CMR using CS3 sequences is feasible, reproducible and analysable using commercially available software. [ABSTRACT FROM AUTHOR]

Background: Hypertrophic cardiomyopathy (HCM) remains the commonest cause of sudden cardiac death among young athletes. Differentiating between physiologically adaptive left ventricular (LV) hypertrophy observed in athletes' hearts and pathological HCM remains challenging. By quantifying the diffusion of water molecules, diffusion tensor imaging (DTI) MRI allows voxelwise characterization of myocardial microstructure.Purpose: To explore microstructural differences between healthy volunteers, athletes, and HCM patients using DTI.Study Type: Prospective cohort.Population: Twenty healthy volunteers, 20 athletes, and 20 HCM patients.Field Strength/sequence: 3T/DTI spin echo.Assessment: In-house MatLab software was used to derive mean diffusivity (MD) and fractional anisotropy (FA) as markers of amplitude and anisotropy of the diffusion of water molecules, and secondary eigenvector angles (E2A)-reflecting the orientations of laminar sheetlets.Statistical Tests: Independent samples t-tests were used to detect statistical significance between any two cohorts. Analysis of variance was utilized for detecting the statistical difference between the three cohorts. Statistical tests were two-tailed. A result was considered statistically significant at P ≤ 0.05.Results: DTI markers were significantly different between HCM, athletes, and volunteers. HCM patients had significantly higher global MD and E2A, and significantly lower FA than athletes and volunteers. (MDHCM = 1.52 ± 0.06 × 10-3 mm2 /s, MDAthletes = 1.49 ± 0.03 × 10-3 mm2 /s, MDvolunteers = 1.47 ± 0.02 × 10-3 mm2 /s, P < 0.05; E2AHCM = 58.8 ± 4°, E2Aathletes = 47 ± 5°, E2Avolunteers = 38.5 ± 7°, P < 0.05; FAHCM = 0.30 ± 0.02, FAAthletes = 0.35 ± 0.02, FAvolunteers = 0.36 ± 0.03, P < 0.05). HCM patients had significantly higher E2A in their thickest segments compared to the remote (E2Athickest = 66.8 ± 7, E2Aremote = 51.2 ± 9, P < 0.05).Data Conclusion: DTI depicts an increase in amplitude and isotropy of diffusion in the myocardium of HCM compared to athletes and volunteers as reflected by increased MD and decreased FA values. While significantly higher E2A values in HCM and athletes reflect steeper configurations of the myocardial sheetlets than in volunteers, HCM patients demonstrated an eccentric rise in E2A in their thickest segments, while athletes demonstrated a concentric rise. Further studies are required to determine the diagnostic capabilities of DTI.Evidence Level: 1 TECHNICAL EFFICACY STAGE: 2. [ABSTRACT FROM AUTHOR]