Cardiovascular magnetic resonance in the evaluation of heart valve disease.

BACKGROUND: Over the last 25 years, cardiovascular magnetic resonance imaging (CMR) has emerged as an alternative to echocardiography for assessment of valvular heart disease (VHD). Although echo remains the first-line imaging modality for the assessment of patients with VHD, CMR can now provide a comprehensive assessment in many instances. Using a combination of techniques, CMR provides information on valve anatomy and enables quantitative analysis of the severity of the valve lesion. MAIN TEXT: In this review, the fundamentals of CMR in assessment of VHD are described, together with its strengths and weaknesses. We detail the utility of CMR for studying all aspects of VHD, including valve anatomy, flow quantification as well as ventricular volumes and function. The optimisation of CMR for evaluating the commonest valve lesions (aortic stenosis, aortic regurgitation, mitral regurgitation, mitral stenosis) as well as in right-sided VHD and prosthetic valves is summarised. The focus of this review is to enable the reader to optimise the use of CMR in his or her own evaluation of heart valve lesions in clinical practice. CONCLUSIONS: CMR can be used for the comprehensive evaluation of VHD. This exciting, non-invasive imaging modality is likely to have increasing utility in the clinical evaluation of patients with VHD

Sex and ethnic differences in the cardiovascular complications of type 2 diabetes

Diabetes mellitus represents a global health concern affecting 463 million adults and is projected to rapidly rise to 700 million people by 2045. Amongst those with type 2 diabetes (T2D), there are recognised differences in the impact of the disease on different sex and ethnic groups. The relative risk of cardiovascular complications between individuals with and without T2D is higher in females than males. People of South Asian heritage are two to four times more likely to develop T2D than white people, but conversely not more likely to experience cardiovascular complications. Differences in the pathophysiological responses in these groups may identify potential areas for intervention beyond glycaemic control. In this review, we highlight key differences of diabetes-associated cardiovascular complications by sex and ethnic background, with a particular emphasis on South Asians. Evidence assessing therapeutic efficacy of new glucose lowering drugs in minority groups is limited and many major cardiovascular outcomes trials do not report ethnic specific data. Conversely, lifestyle intervention and bariatric surgery appear to have similar benefits regardless of sex and ethnic groups. We encourage future studies with better representation of women and ethnic minorities that will provide valuable data to allow better risk stratification and tailored prevention and management strategies to improve cardiovascular outcomes in T2D

Differences in native T1 and native T2 mapping between patients on hemodialysis and control subjects

PurposeMyocardial native T1 is a potential measure of myocardial fibrosis, but concerns remain over the potential influence of myocardial edema to increased native T1 signal in subjects prone to fluid overload. This study describes differences in native T2 (typically raised in states of myocardial edema) and native T1 times in patients on hemodialysis by comparing native T1 and native T2 times between subjects on hemodialysis to an asymptomatic control group. Reproducibility of these sequences was tested.MethodsSubjects were recruited prospectively and underwent 3 T-cardiac MRI with acquisition of native T1 and native T2 maps. Between group differences in native T1 and T2 maps were assessed using one-way ANOVAs. 30 subjects underwent test-retest scans within a week of their original scan to define sequence reproducibility.Results261 subjects completed the study (hemodialysis n = 124, control n = 137). Native T1 times were significantly increased in subjects on hemodialysis compared to control subjects (1259 ms ± 51 vs 1212 ms ± 37, p ConclusionsThe increased native T1 signal demonstrated in subjects on hemodialysis occurs independently of differences in native T2 and the two parameters are not orthogonal. Elevated native T1 in patients on hemodialysis may be driven by water related to myocardial fibrosis rather than edema from volume overload.</div

Plasma P‐selectin is a predictor of mortality in heart failure with preserved ejection fraction

AimsThe aim of the study was to assess the association of P‐selectin with outcomes in heart failure with preserved ejection fraction (HFpEF).Methods and resultsThis is a prospective, observational study of 130 HFpEF patients who underwent clinical profiling, blood sampling, 6 min walk testing, Minnesota Living with Heart Failure Questionnaire evaluation, echocardiography, cardiovascular magnetic resonance imaging, calculation of the Meta‐Analysis Global Group in Chronic Heart Failure (MAGGIC) risk scores, and blinded plasma P‐selectin measurement. Patients were followed up for the endpoint of all‐cause mortality. The HFpEF subgroup with higher P‐selectin levels [overall median 26 372, inter‐quartile range (19 360–34 889) pg/mL] was associated with lower age, higher heart rate, less prevalent atrial fibrillation, more frequent current smoking status, and lower right ventricular end‐diastolic volumes. During follow‐up (median 1428 days), there were 38 deaths. Following maximal sensitivity and specificity receiver operating characteristic curve analysis, P‐selectin levels above 35 506 pg/mL were associated with greater risk of all‐cause mortality [hazard ratio (HR) 2.700; 95% confidence interval (CI) 1.416–5.146; log‐rank P = 0.002]. Following multivariable Cox proportional hazards regression analysis and when added to MAGGIC scores, only P‐selectin (adjusted HR 1.707; 95% CI 1.099–2.650; P ConclusionsPlasma P‐selectin is an independent predictor of mortality and provides incremental prognostic information beyond MAGGIC scores in HFpEF.</div

Interrelationship between micronutrients and cardiovascular structure and function in type 2 diabetes

Micronutrients are important for normal cardiovascular function. They may play a role in the increased risk of cardiovascular disease observed in people with type 2 diabetes (T2D) and T2D-related heart failure. The aims of this study were to (1) examine micronutrient status in people with T2D v. healthy controls; (2) assess any changes following a nutritionally complete meal replacement plan (MRP) compared with routine care; (3) determine if any changes were associated with changes in cardiovascular structure/function. This was a secondary analysis of data from a prospective, randomised, open-label, blinded end-point trial of people with T2D, with a nested case-control [NCT02590822]. Anthropometrics, cardiac resonance imaging and fasting blood samples (to quantify vitamins B1, B6, B12, D and C; and iron and ferritin) were collected at baseline and 12 weeks following the MRP or routine care. Comparative data in healthy controls were collected at baseline. A total of eighty-three people with T2D and thirty-six healthy controls were compared at baseline; all had micronutrient status within reference ranges. Vitamin B1 was higher (148.9 v. 131â .7; P 0.01) and B6 lower (37.3 v. 52.9; P 0.01) in T2D v. controls. All thirty participants randomised to routine care and twenty-four to the MRP completed the study. There was an increase in vitamins B1, B6, D and C following the MRP, which were not associated with changes in cardiovascular structure/function. In conclusion, changes in micronutrient status following the MRP were not independently associated with improvements in cardiovascular structure/function in people with T2D

Fibroblast-growth-factor-23 in heart failure with preserved ejection fraction: relation to exercise capacity and outcomes

AimsThis study aimed to assess plasma fibroblast growth factor 23 (FGF23) in patients with heart failure with preserved ejection fraction (HFpEF) and its relation to inflammation, renal function, clinical and imaging characteristics, exercise capacity, and prognosis.Methods and resultsWe performed a prospective, observational study of 172 age‐matched and sex‐matched subjects (HFpEF n = 130; controls n = 42, age 73 ± 9, female 50%) who underwent plasma biomarker sampling, echocardiography, cardiac magnetic resonance imaging, and 6 min walk testing (6MWT). The primary endpoint was the composite of all‐cause death or HF hospitalization. FGF23 was higher in HFpEF compared with controls (62 [42–105] vs. 34 [22–41] pg/mL, P ConclusionsPlasma FGF23 is higher in HFpEF compared with age‐matched and sex‐matched controls and is strongly associated with exercise incapacity and prognosis. FGF23 correlates with plasma markers of inflammation and renal impairment.</div

The impact of lifestyle intervention on left atrial function in type 2 diabetes: results from the DIASTOLIC study

Aerobic exercise training and low energy diets have been shown to improve left ventricular remodelling and diastolic function in adults with type 2 diabetes (T2D), albeit with differential effects. The impact of these lifestyle interventions on left atrial (LA) function, however, has not previously been reported. The DIASTOLIC study was a prospective, randomised, open-label, blind endpoint trial, in which 90 people with obesity and T2D and no prevalent cardiovascular disease were randomised to a 12-week intervention of: (i) routine care, (ii) aerobic exercise training, or (iii) low energy (≈ 810 kcal/day) meal replacement plan (MRP). Cardiac magnetic resonance (CMR) imaging was performed pre- and post-intervention. Image analysis included LA volumes (LAV), emptying fraction (LAEF), and LA strain (LAS) corresponding to LA reservoir (LAS-r), conduit (LAS-cd), and booster pump (LAS-bp) function. 73 participants with T2D (mean age 50 ± 6 years, 62% male, body mass index (BMI) 36.1 ± 5.3 kg/m2) completed the trial and had analysable LA images. There was no significant change in CMR measured LA volumetric function (LAV/LAEF) in any group. The routine care group showed no significant change in BMI or LAS. In the MRP group, there were significant reductions in BMI (4.5 kg/m2) and a significant increase in LAS-r and LAS-bp (29.9 ± 7.0 to 32.3 ± 7.0%, p = 0.036 and 14.6 ± 5.3 to 17.2 ± 3.7%, p = 0.034). The exercise group showed a small reduction in BMI (0.49 kg/m2), with no significant change in LAS. Compared to routine care, weight loss via a 12-week MRP, led to improvements in LA filling and contractile function in adults with T2D and obesity. However, these within-group changes were not statistically significant on between-group comparison. ClinicalTrials.gov Identifier: NCT02590822.</p

Left atrial ejection fraction and outcomes in heart failure with preserved ejection fraction

The aim of this study was to determine whether left atrial ejection fraction (LAEF) quantified with cardiovascular magnetic resonance (CMR) was different between heart failure with preserved ejection fraction (HFpEF) and controls, and its relation to prognosis. As part of our single-centre, prospective, observational study, 188 subjects (HFpEF n = 140, controls n = 48) underwent phenotyping with contrast-enhanced CMR, transthoracic echocardiography, blood sampling and six-minute walk testing. LAEF was calculated using the biplane method. Atrial fibrillation (AF) was present in 43 (31%) of HFpEF subjects. Overall, LAEF (%) was lower in HFpEF patients inclusive of AF (32 ± 16) or those in sinus rhythm alone (41 ± 12) compared to controls (51 ± 11), p < 0.0001. LAEF correlated inversely with maximal and minimal left atrial volumes indexed (r = − 0.602, r = − 0.762), and plasma N-terminal pro-atrial natriuretic peptide (r = − 0.367); p < 0.0001. During median follow-up (1429 days), there were 67 composite events of all-cause death or hospitalization for heart failure (22 deaths, 45 HF hospitalizations) in HFpEF. Lower LAEF (below median) was associated with an increased risk of composite endpoints (Log-Rank: all p = 0.028; sinus p = 0.036). In multivariable Cox regression analysis, LAEF (adjusted hazard ratio [HR] 0.767, 95% confidence interval [CI] 0.591–0.996; p = 0.047) and indexed extracellular volume (HR 1.422, CI 1.015–1.992; p = 0.041) were the only parameters that remained significant when added to a base prognostic model comprising age, prior HF hospitalization, diastolic blood pressure, lung disease, NYHA, six-minute-walk-test-distance, haemoglobin, creatinine and B-type natriuretic peptide. CMR-derived LAEF is lower in HFpEF compared to healthy controls and is a strong prognostic biomarker

Impact of remission of type 2 diabetes on cardiovascular structure and function, exercise capacity and risk profile: a propensity matched analysis

Background and aims: Type 2 diabetes (T2D) confers high risk of heart failure frequently with evidence of cardiovascular structural and functional abnormalities before symptom onset. The effects of remission of T2D on cardiovascular structure and function are unknown. The aim of this work was to describe the impact of remission of T2D, beyond weight-loss and glycaemia, on cardiovascular structure and function and exercise capacity. Materials and methods: Obese adults with T2D without cardiovascular disease were recruited into the "Prevalence and determinants of subclinical cardiovascular dysfunction in adults with type 2 diabetes" study (PREDICT). PREDICT is a prospective cross-sectional, case-control study. All participants underwent multimodality cardiovascular imaging, cardiopulmonary exercise testing, and cardiometabolic profiling. T2D-remission cases (HbA1c Results: The average exposure to T2D was less than six years across both groups and the duration of remission was 4.2±2.5 years. The variance between groups for demographic, anthropometry and metabolic profile was expected based on the study design. T2D-remission was associated with lower leptin-adiponectin ratio (0.75 (0.37,1.50) vs. 2.24 (1.43,4.10)), hepatic steatosis (3.20% (2.20,7.33) vs. 9.40 (4.80,15.20)) and triglycerides (1.45mmol/l (0.96,1.74) vs. 1.69 (1.3,2.2)), a trend towards greater exercise capacity and significantly lower VE/VCO2 slope vs. active-T2D (27.74 ± 3.95 vs. 30.52 ± 5.46) all p Conclusion: T2D-remission is associated with improved metabolic risk profile and ventilatory response to exercise without concomitant improvements in cardiovascular structure or function. There is a requirement for continued attention to risk factor control for this important patient population.</p

Circulating sphingolipids and relationship to cardiac remodelling before and following a low-energy diet in asymptomatic Type 2 Diabetes

Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogenous multi-system syndrome with limited efficacious treatment options. The prevalence of Type 2 diabetes (T2D) continues to rise and predisposes patients to HFpEF, and HFpEF remains one of the biggest challenges in cardiovascular medicine today. Novel therapeutic targets are required to meet this important clinical need. Deep phenotyping studies including -OMIC analyses can provide important pathogenic information to aid the identification of such targets. The aims of this study were to determine; 1) the impact of a low-energy diet on plasma sphingolipid/ceramide profiles in people with T2D compared to healthy controls and, 2) if the change in sphingolipid/ceramide profile is associated with reverse cardiovascular remodelling. Methods: Post-hoc analysis of a randomised controlled trial (NCT02590822) including adults with T2D with no cardiovascular disease who completed a 12-week low-energy (∼810 kcal/day) meal-replacement plan (MRP) and matched healthy controls (HC). Echocardiography, cardiac MRI and a fasting blood for lipidomics were undertaken pre/post-intervention. Candidate biomarkers were identified from case–control comparison (fold change > 1.5 and statistical significance p < 0.05) and their response to the MRP reported. Association between change in biomarkers and change indices of cardiac remodelling were explored. Results: Twenty-four people with T2D (15 males, age 51.1 ± 5.7 years), and 25 HC (15 male, 48.3 ± 6.6 years) were included. Subjects with T2D had increased left ventricular (LV) mass:volume ratio (0.84 ± 0.13 vs. 0.70 ± 0.08, p < 0.001), increased systolic function but impaired diastolic function compared to HC. Twelve long-chain polyunsaturated sphingolipids, including four ceramides, were downregulated in subjects with T2D at baseline. Three sphingomyelin species and all ceramides were inversely associated with LV mass:volume. There was a significant increase in all species and shift towards HC following the MRP, however, none of these changes were associated with reverse cardiac remodelling. Conclusion: The lack of association between change in sphingolipids/ceramides and reverse cardiac remodelling following the MRP casts doubt on a causative role of sphingolipids/ceramides in the progression of heart failure in T2D. Trial registration: NCT02590822