Manganese-enhanced Magnetic Resonance Imaging in Dilated Cardiomyopathy and Hypertrophic Cardiomyopathy.

Patients with dilated cardiomyopathy (n= 10) or hypertrophic cardiomyopathy (n= 17) underwent both gadoliniumand manganese contrast-enhanced magnetic resonance imaging and were compared with healthy volunteers(n= 20). Differential manganese uptake (Ki) was assessed using a two-compartment Patlak model. Compared withhealthy volunteers, reduction in T1 with manganese-enhanced magnetic resonance imaging was lower in patientswith dilated cardiomyopathy [mean reduction 257 ± 45 (21%) vs. 288 ± 34 (26%) ms,P< 0.001], with higher T1 at40 min (948 ± 57 vs. 834 ± 28 ms,P< 0.0001). In patients with hypertrophic cardiomyopathy, reductions in T1 wereless than healthy volunteers [mean reduction 251 ± 86 (18%) and 277 ± 34 (23%) vs. 288 ± 34 (26%) ms, with andwithout fibrosis respectively,P< 0.001]. Myocardial manganese uptake was modelled, rate of uptake was reducedin both dilated and hypertrophic cardiomyopathy in comparison with healthy volunteers (meanKi19 ± 4, 19 ± 3,and 23 ± 4 mL/100 g/min, respectively;P= 0.0068). In patients with dilated cardiomyopathy, manganese uptake ratecorrelated with left ventricular ejection fraction (r2= 0.61,P= 0.009). Rate of myocardial manganese uptake demon-strated stepwise reductions across healthy myocardium, hypertrophic cardiomyopathy without fibrosis and hyper-trophic cardiomyopathy with fibrosis providing absolute discrimination between the healthy myocardium andfibrosed myocardium (meanKi23 ± 4, 19 ± 3, and 13 ± 4 mL/100 g/min, respectively;P< 0.0001)

MECHANISMS IN ENDOCRINOLOGY: Diabetic cardiomyopathy: pathophysiology and potential metabolic interventions state of the art review

Heart failure is a major cause of morbidity and mortality in type 2 diabetes. Type 2 diabetes contributes to the development of heart failure through a variety of mechanisms, including disease-specific myocardial structural, functional and metabolic changes. This review will focus on the contemporary contributions of state of the art non-invasive technologies to our understanding of diabetic cardiomyopathy, including data on cardiac disease phenotype, cardiac energy metabolism and energetic deficiency, ectopic and visceral adiposity, diabetic liver disease, metabolic modulation strategies and cardiovascular outcomes with new classes of glucose-lowering therapies

Characterizing heart failure with preserved and reduced ejection fraction: An imaging and plasma biomarker approach.

IntroductionThe pathophysiology of heart failure with preserved ejection fraction (HFpEF) remains incompletely defined. We aimed to characterize HFpEF compared to heart failure with reduced ejection fraction (HFrEF) and asymptomatic hypertensive or non-hypertensive controls.Materials and methodsProspective, observational study of 234 subjects (HFpEF n = 140; HFrEF n = 46, controls n = 48, age 73±8, males 49%) who underwent echocardiography, cardiovascular magnetic resonance imaging (CMR), plasma biomarker analysis (panel of 22) and 6-minute walk testing (6MWT). The primary end-point was the composite of all-cause mortality and/or HF hospitalization.ResultsCompared to controls both HF groups had lower exercise capacity, lower left ventricular (LV) EF, higher LV filling pressures (E/E', B-type natriuretic peptide [BNP], left atrial [LA] volumes), more right ventricular (RV) systolic dysfunction, more focal and diffuse fibrosis and higher levels of all plasma markers. LV remodeling (mass/volume) was different between HFpEF (concentric, 0.68±0.16) and HFrEF (eccentric, 0.47±0.15); pConclusionsHFpEF is a distinct pathophysiological entity compared to age- and sex-matched HFrEF and controls. HFpEF and HFrEF are associated with similar adverse outcomes. Inflammation is common in both HF phenotypes but cardiomyocyte stretch/stress is greater in HFrEF

Fibro-inflammatory recovery and type 2 diabetes remission following a low calorie diet but not exercise training: A secondary analysis of the DIASTOLIC randomised controlled trial

AimsTo investigate the relationship between fibro-inflammatory biomarkers and cardiovascular structure/function in people with Type 2 Diabetes (T2D) compared to healthy controls and the effect of two lifestyle interventions in T2D.MethodsData were derived from the DIASTOLIC randomised controlled trial (RCT) and includes a comparison between those with T2D and the matched healthy volunteers recruited at baseline. Adults with T2D without cardiovascular disease (CVD) were randomized to a 12-week intervention either: (1) exercise training, (2) a low-energy (∼810 kcal/day) meal-replacement plan (MRP) or (3) standard care. Principal Component and Fisher's linear discriminant analysis were used to investigate the relationships between MRI acquired cardiovascular outcomes and fibro-inflammatory biomarkers in cases versus controls and pre- and post-intervention in T2D.ResultsAt baseline, 83 people with T2D (mean age 50.5 ± 6.4; 58% male) and 36 healthy controls (mean age 48.6 ± 6.2; 53% male) were compared and 76 people with T2D completed the RCT for pre- post-analysis. Compared to healthy controls, subjects with T2D had adverse cardiovascular remodelling and a fibro-inflammatory profile (20 differentially expressed biomarkers). The 3D data visualisations showed almost complete separation between healthy controls and those with T2D, and a marked shift towards healthy controls following the MRP (15 biomarkers significantly changed) but not exercise training.ConclusionsFibro-inflammatory pathways and cardiovascular structure/function are adversely altered before the onset of symptomatic CVD in middle-aged adults with T2D. The MRP improved the fibro-inflammatory profile of people with T2D towards a more healthy status. Long-term studies are required to assess whether these changes lead to continued reverse cardiac remodelling and prevent CVD

Chronic infarct size after spontaneous coronary artery dissection: implications for pathophysiology and clinical management

Aims: To report the extent and distribution of myocardial injury and its impact on left ventricular systolic function with cardiac magnetic resonance imaging (CMR) following spontaneous coronary artery dissection (SCAD) and to investigate predictors of myocardial injury. Methods and results: One hundred and fifty-eight angiographically confirmed SCAD-survivors (98% female) were phenotyped by CMR and compared in a case–control study with 59 (97% female) healthy controls (44.5 ± 8.4 vs. 45.0 ± 9.1 years). Spontaneous coronary artery dissection presentation was with non-ST-elevation myocardial infarction in 95 (60.3%), ST-elevation myocardial infarction (STEMI) in 52 (32.7%), and cardiac arrest in 11 (6.9%). Left ventricular function in SCAD-survivors was generally well preserved with small reductions in ejection fraction (57 ± 7.2% vs. 60 ± 4.9%, P &lt; 0.01) and increases in left ventricular dimensions (end-diastolic volume: 85 ± 14 mL/m2 vs. 80 ± 11 mL/m2, P &lt; 0.05; end-systolic volume: 37 ± 11 mL/m2 vs. 32 ± 7 mL/m2, P &lt;0.01) compared to healthy controls. Infarcts were small with few large infarcts (median 4.06%; range 0–30.9%) and 39% having no detectable late gadolinium enhancement (LGE). Female SCAD patients presenting with STEMI had similar sized infarcts to female Type-1 STEMI patients age &lt;75 years. Multivariate modelling demonstrated STEMI at presentation, initial TIMI 0/1 flow, multivessel SCAD, and a Beighton score &gt;4 were associated with larger infarcts [&gt;10% left ventricular (LV) mass]. Conclusion: The majority of patients presenting with SCAD have no or small infarctions and preserved ejection fraction. Patients presenting with STEMI, TIMI 0/1 flow, multivessel SCAD and those with features of connective tissue disorders are more likely to have larger infarcts

Subclinical cardiovascular dysfunction in adults with type 2 diabetes: characterisation and lifestyle interventions

BackgroundPeople with type 2 diabetes (T2D) are at increased risk of heart failure. Various measures of subclinical cardiovascular dysfunction have been reported, but it is unclear how these relate to functional limitation or whether they are reversible with lifestyle interventions.ObjectivesTo comprehensively describe cardiovascular function in a multi-ethnic, asymptomatic population with T2D, and determine whether this is improved by a low-energy meal replacement plan (MRP) diet or exercise.MethodsA comparison of adults with and without T2D and no cardiovascular disease was undertaken. A subset undertook a prospective, randomised, open-label, blinded endpoint (PROBE) trial and were assigned a 12-week intervention of: 1) routine care; 2) supervised exercise or 3) MRP. Echocardiography, cardiopulmonary exercise testing and cardiovascular magnetic resonance (CMR) were performed at baseline and post-intervention. The primary outcome was change in left ventricular (LV) peak early diastolic strain rate (PEDSR), measured by CMR.ResultsAt baseline, 247 adults with T2D and 78 controls were compared. Subjects with T2D had concentric LV remodelling, diastolic dysfunction, aortic stiffening, reduced myocardial perfusion, and markedly lower peak VO2. Key clinical determinants of cardiovascular dysfunction were diabetes duration, body mass index (BMI), smoking history, and systolic blood pressure (BP). MPR and diastolic filling were independently associated with peak VO2.Seventy-six T2Ds completed the PROBE trial (30 routine care, 22 exercise, and 24 MRP). The MRP arm lost weight, improved BP, glycaemia, LV mass:volume, and aortic stiffness. The exercise arm had negligible weight loss but increased exercise capacity. PEDSR increased in the exercise arm versus routine care (p=0.002) but did not improve with the MRP compared to routine care.ConclusionsConcentric LV remodelling, diastolic dysfunction, aortic stiffening, and reduced MPR are key components of subclinical cardiovascular dysfunction in T2D. Exercise training improved diastolic function and despite beneficial effects on weight, glycaemic control, concentric LV remodelling and aortic stiffness, an MRP did not improve diastolic function.</div