Defining myocardial fibrosis in haemodialysis patients with non-contrast cardiac magnetic resonance

Background: Extent of myocardial fibrosis (MF) determined using late gadolinium enhanced (LGE) predicts outcomes, but gadolinium is contraindicated in advanced renal disease. We assessed the ability of native T1-mapping to identify and quantify MF in aortic stenosis patients (AS) as a model for use in haemodialysis patients. Methods: We compared the ability to identify areas of replacement-MF using native T1-mapping to LGE in 25 AS patients at 3 T. We assessed agreement between extent of MF defined by LGE full-width-half-maximum (FWHM) and the LGE 3-standard-deviations (3SD) in AS patients and nine T1 thresholding-techniques, with thresholds set 2-to-9 standard-deviations above normal-range (1083 ± 33 ms). A further technique was tested that set an individual T1-threshold for each patient (T11SD). The technique that agreed most strongly with FWHM or 3SD in AS patients was used to compare extent of MF between AS (n = 25) and haemodialysis patients (n = 25). Results: Twenty-six areas of enhancement were identified on LGE images, with 25 corresponding areas of discretely increased native T1 signal identified on T1 maps. Global T1 was higher in haemodialysis than AS patients (1279 ms ± 5. 8 vs 1143 ms ± 12.49, P < 0.01). No signal-threshold technique derived from standard-deviations above normal-range associated with FWHM or 3SD. T11SD correlated with FWHM in AS patients (r = 0.55) with moderate agreement (ICC = 0.64), (but not with 3SD). Extent of MF defined by T11SD was higher in haemodialysis vs AS patients (21.92% ± 1 vs 18.24% ± 1.4, P = 0.038), as was T1 in regions-of-interest defined as scar (1390 ± 8.7 vs 1276 ms ± 20.5, P < 0.01). There was no difference in the relative difference between remote myocardium and regions defined as scar, between groups (111.4 ms ± 7.6 vs 133.2 ms ± 17.5, P = 0.26). Conclusions: Areas of MF are identifiable on native T1 maps, but absolute thresholds to define extent of MF could not be determined. Histological studies are needed to assess the ability of native-T1 signal-thresholding techniques to define extent of MF in haemodialysis patients. Data is taken from the PRIMID-AS (NCT01658345) and CYCLE-HD studies (ISRCTN11299707

Role of Cardiac Magnetic Resonance Imaging measured Myocardial Perfusion Reserve in asymptomatic patients with Aortic Stenosis: a comparison with Exercise Testing

Background: The management of asymptomatic patients with severe aortic stenosis (AS) is controversial. Cardiovascular Magnetic Resonance (CMR) imaging has been proposed as a potential prognostic marker that may help select patients for aortic valve replacement (AVR). Aims: To establish: the reproducibility of novel CMR techniques; determinants of peak VO2 and MPR; effect of Ranolazine; and predictors of outcome in asymptomatic moderate-severe AS, and compare MPR to exercise testing as predictors of outcome. Methods: The PRIMID-AS study was a multi-centre, prospective, observational study, with blinded analysis of imaging data. AS patients and controls underwent: trans-thoracic echocardiogram (TTE), symptom-limited cardiopulmonary exercise test (CPET), adenosine stress CMR at 3T and a CT calcium score, and were followed up for a minimum of 12 months, or until a primary endpoint occurred (symptom-driven AVR, MACE or cardiovascular death). Additionally a pilot study on the short-term effect of Ranolazine in asymptomatic patients with moderate-severe AS was carried out in 19 patients. Results: 174 patients (age 66.2±13.34 years, 76% male, aortic valve area index 0.57±0.14 cm2/m2) were recruited as part of PRIMID-AS study, in addition to 23 age- and comorbidity-matched controls. Patients showed evidence of LV remodeling and impaired MPR, but preserved exercise capacity compared to controls, suggesting a state of ‘compensation’. MPR and longitudinal strain were independently associated with age- and sex-corrected peak VO2, whilst extra-cellular volume (ECV) and AS severity were independently associated with MPR. A primary outcome occurred in 39 (22.4%) patients. MPR showed moderate association with outcome (area under curve (AUC)=0.62 (0.52-0.71, p=0.019), as did exercise testing (AUC=0.58 (0.49-0.67, p=0.071), with no significant difference between the two. Ranolazine did not improve diastolic function or MPR significantly. Conclusions: MPR was associated with exercise capacity and symptom-onset in initially asymptomatic patients with AS, but with moderate accuracy and was not superior to symptom-limited exercise testing

Shared decision making in athletes with cardiovascular disease: what we can learn from a masters athlete

A 75-year-old male cyclist began suffering from palpitations on exertion. Symptoms terminated spontaneously with cessation of physical activity. The episodes caused significant distress with an impact on physical performance and quality of life. An echocardiogram showed a dilated left atrium, and an exercise ECG demonstrated that episodes of atrial fibrillation developed when his ventricular rate was above 140 beats per minute. Rate control could not be offered due to a history of sinus bradycardia nor rhythm control due to low likelihood of success. Anticoagulant therapy was commenced but discontinued at patient request as he considered risks to outweigh benefits given his desire to continue cycling. Management of athletes with atrial fibrillation is based on guidelines for the general population; however, treatment goals for athletes may differ. Shared decision making is essential to allow patients to make informed decisions about their care, accepting that individuals view treatment risks and benefits differently

Myocardial Calcium Handling in Type 2 Diabetes: A Novel Therapeutic Target

Type 2 diabetes (T2D) is a multisystem disease with rapidly increasing global prevalence. Heart failure has emerged as a major complication of T2D. Dysregulated myocardial calcium handling is evident in the failing heart and this may be a key driver of cardiomyopathy in T2D, but until recently this has only been demonstrated in animal models. In this review, we describe the physiological concepts behind calcium handling within the cardiomyocyte and the application of novel imaging techniques for the quantification of myocardial calcium uptake. We take an in-depth look at the evidence for the impairment of calcium handling in T2D using pre-clinical models as well as in vivo studies, following which we discuss potential novel therapeutic approaches targeting dysregulated myocardial calcium handling in T2D

MOESM1 of Effect of late sodium current inhibition on MRI measured diastolic dysfunction in aortic stenosis: a pilot study

Additional file 1: Tabble S1. Tagging measured PEDSR for FAS population: baseline vs. week-6 vs. week-10 (n=13)

The role of 4-dimensional flow in the assessment of bicuspid aortic valve and its valvulo-aortopathies

Bicuspid aortic valve is the most common congenital cardiac malformation and the leading cause of aortopathy and aortic stenosis in younger patients. Aortic wall remodelling secondary to altered haemodynamic flow patterns, changes in peak velocity, and wall shear stress may be implicated in the development of aortopathy in the presence of bicuspid aortic valve and dysfunction. Assessment of these parameters as potential predictors of disease severity and progression is thus desirable. The anatomic and functional information acquired from 4D flow MRI can allow simultaneous visualisation and quantification of the pathological geometric and haemodynamic changes of the aorta. We review the current clinical utility of haemodynamic quantities including velocity, wall sheer stress and energy losses, as well as visual descriptors such as vorticity and helicity, and flow direction in assessing the aortic valve and associated aortopathies.</p

Effect of late sodium current inhibition on MRI measured diastolic dysfunction in aortic stenosis: a pilot study

BACKGROUND: Ranolazine is a new anti-anginal drug that acts via late sodium current inhibition, and has been shown to improve diastolic dysfunction in isolated myocytes. Diastolic dysfuntion is common in patients with aortic stenosis (AS), and precedes symptom development and systolic dysfunction. The purpose of this study was to assess the effects of ranolazine on peak early diastolic strain rate (PEDSR) and exercise capacity in patients with AS. METHODS: Patients with asymptomatic moderate to severe AS and diastolic dysfunction underwent trans-thoracic echocardiography, exercise testing and cardiac magnetic resonance (CMR) imaging at baseline, 6 weeks after commencing ranolazine and at 10 weeks (4 weeks after discontinuation). Diastolic function was assessed using PEDSR measured on tagged CMR images. RESULTS: Fifteen patients (peak pressure gradient 48.8 ± 12.4 mmHg, mean pressure gradient 27.1 ± 7.5 mmHg, aortic valve area 1.26 ± 0.31 cm(2)) completed the week-6 visit and 13 completed the final visit. Global PEDSR did not significantly increase from baseline (0.79 ± 0.15) to week-6 (0.86 ± 0.18, p = 0.198). There was a borderline significant increase in total exercise duration from 10.47 ± 3.68 min to 11.60 ± 3.25 min (p = 0.06). CONCLUSION: This small pilot study did not show a significant improvement in diastolic function with the use of ranolazine in asymptomatic patients with moderate-severe AS. Further studies with a larger population may be indicated. EduraCT number 2011-000111-26

21 The Effect of Severe Aortic Stenosis on Aortic Haemodynamic Flow-Parameter Differences Between Bicuspid and Tri-leaflet Valve Morphology: a 4D Flow Study

Introduction Bicuspid aortic valve (BAV) is associated with earlier onset valvulo-aortopathy including aortic stenosis (AS) and aortic root dilatation than tri-leaflet aortic valves (TAV). Altered aortic haemodynamic flow patterns are linked with increased risk of BAV-associated aortopathy.1–3 Incremental effects of AS on these are unclear. Materials and Methods 4D flow cardiovascular magnetic resonance (4DF-CMR) was performed on 32 patients (11 BAV, 21 TAV, mean age 68 ± 10 years) with severe symptomatic AS (aortic valve area ≤ 1 cm2) and 17 healthy controls (8 BAV, 9 TAV, mean age 57 ± 7 years). In-plane peak velocity and maximum wall shear stress (WSS) were evaluated from 2D analysis planes at the aortic root and distal ascending aorta (AAo) using commercial software. Peak systolic 3D volumetric velocities and vorticities averaged over the AAo (aortic root to level of pulmonary artery bifurcation) were generated using in-house Matlab code. All comparisons were adjusted for age and diastolic blood pressure. Results In-plane peak velocities (300 ± 74 vs 176 ± 53 cm/s) and WSS at the AAo, as well as volume averaged peak velocities (434 ± 92 vs 239 ± 127 cm/s) and vorticities (152 ± 26 vs 91 ± 26 rad) were significantly higher (p Discussion 4DF-CMR demonstrated pathological aortic haemodynamic patterns in patients with severe AS compared to controls. Haemodynamic differences were also measurable in the ascending aorta of asymptomatic BAV compared to TAV controls. These differences were no longer significant in the presence of AS. Conclusion Abnormal flow patterns in asymptomatic BAV become indistinguishable from those of TAV in the presence of severe AS, suggesting AS induces similar pathological changes in aortic haemodynamics, independent of valve morphology.</p

A systematic review of micro-RNAs in aortic stenosis and cardiac fibrosis

Aortic stenosis (AS) is the commonest valve lesion requiring surgery in the Western world. The presence of myocardial fibrosis is associated with mortality even after valve replacement. MicroRNAs could serve as biomarkers of fibrosis and risk stratify patients for earlier intervention. This study aimed to systematically review reports of micro‐RNA (miR) associated with fibrosis in AS and identify potential biomarkers. We searched EMBASE, Medline, and Web of Science up to May 2020. Studies that reported on the role of miRs in AS and cardiac fibrosis were included. Study quality was assessed using the Newcastle‐Ottawa scale. Of 4230 reports screened, 25 were included. All studies were of low to moderate quality. MiRs were analyzed in myocardial tissue (n = 10), aortic valve tissue (n = 5), plasma (n = 5), and serum (n = 5). A total of 365 miRs were reported, of which only a few were reported in more than one paper (3 in the myocardium, 5 in the aortic valve, and 1 in plasma). miR‐21 was upregulated in plasma and myocardial tissue. MiR‐19b was downregulated in the myocardium. Papers reporting myocardial miR‐1 contradicted each other, and miR‐133a was associated with increased left ventricular mass regression post‐surgery. In the aortic valve, miRs‐665, 602 and 939 were downregulated, and miRs‐193b and 214 were upregulated. The data on miR in fibrosis in AS is scarce and of low to moderate quality. Further studies are needed to identify novel miRs as biomarkers, especially at an earlier asymptomatic phase of the disease.</p

Comparison of semi-automated methods to quantify infarct size and area at risk by cardiovascular magnetic resonance imaging at 1.5T and 3.0T field strengths.

Background: There is currently no gold standard technique for quantifying infarct size (IS) and ischaemic area-at-risk (AAR [oedema]) on late gadolinium enhancement imaging (LGE) and T2-weighted short tau inversion recovery imaging (T2w-STIR) respectively. This study aimed to compare the accuracy and reproducibility of IS and AAR quantification on LGE and T2w-STIR imaging using Otsu’s Automated Technique (OAT) with currently used methods at 1.5T and 3.0T post acute ST-segment elevation myocardial infarction (STEMI). Methods: Ten patients were assessed at 1.5T and 10 at 3.0T. IS was assessed on LGE using 5–8 standard-deviation thresholding (5-8SD), full-width half-maximum (FWHM) quantification and OAT. AAR was assessed on T2w-STIR using 2SD and OAT. Accuracy was assessed by comparison with manual quantification. Interobserver and intraobserver variabilities were assessed using Intraclass Correlation Coefficients and Bland-Altman analysis. IS using each technique was correlated with left ventricular ejection fraction (LVEF). Results: FWHM and 8SD-derived IS closely correlated with manual assessment at both field strengths (1.5T: 18.3 ± 10.7% LV Mass [LVM] with FWHM, 17.7 ± 14.4% LVM with 8SD, 16.5 ± 10.3% LVM with manual quantification; 3.0T: 10.8 ± 8.2% LVM with FWHM, 11.4 ± 9.0% LVM with 8SD, 11.5 ± 9.0% LVM with manual quantification). 5SD and OAT overestimated IS at both field strengths. OAT, 2SD and manually quantified AAR closely correlated at 1.5T, but OAT overestimated AAR compared with manual assessment at 3.0T. IS and AAR derived by FWHM and OAT respectively had better reproducibility compared with manual and SD-based quantification. FWHM IS correlated strongest with LVEF. Conclusions: FWHM quantification of IS is accurate, reproducible and correlates strongly with LVEF, whereas 5SD and OAT overestimate IS. OAT accurately assesses AAR at 1.5T and with excellent reproducibility. OAT overestimated AAR at 3.0T and thus cannot be recommended as the preferred method for AAR quantification at 3.0T