The impact of water exchange on estimates of myocardial extracellular volume calculated using contrast enhanced T1 measurements: A preliminary analysis in patients with severe aortic stenosis.

PURPOSE: Guidelines recommend measuring myocardial extracellular volume (ECV) using T1 -mapping before and 10-30 min after contrast agent administration. Data are then analyzed using a linear model (LM), which assumes fast water exchange (WX) between the ECV and cardiomyocytes. We investigated whether limited WX influences ECV measurements in patients with severe aortic stenosis (AS). METHODS: Twenty-five patients with severe AS and 5 healthy controls were recruited. T1 measurements were made on a 3 T Siemens system using a multiparametric saturation-recovery single-shot acquisition (a) before contrast; (b) 4 min post 0.05 mmol/kg gadobutrol; and (c) 4 min, (d) 10 min, and (e) 30 min after an additional gadobutrol dose (0.1 mmol/kg). Three LM-based ECV estimates, made using paired T1 measurements (a and b), (a and d), and (a and e), were compared to ECV estimates made using all 5 T1 measurements and a two-site exchange model (2SXM) accounting for WX. RESULTS: Median (range) ECV estimated using the 2SXM model was 25% (21%-39%) for patients and 26% (22%-29%) for controls. ECV estimated in patients using the LM at 10 min following a cumulative contrast dose of 0.15 mmol/kg was 21% (17%-32%) and increased significantly to 22% (19%-35%) at 30 min (p = 0.0001). ECV estimated using the LM was highest following low dose gadobutrol, 25% (19%-38%). CONCLUSION: Current guidelines on contrast agent dose for ECV measurements may lead to underestimated ECV in patients with severe AS because of limited WX. Use of a lower contrast agent dose may mitigate this effect.

Update on muscle imaging in myositis.

PURPOSE OF REVIEW: Imaging techniques such as MRI, ultrasound and PET/computed tomography (CT) have roles in the detection, diagnosis and management of myositis or idiopathic inflammatory myopathy (IIM). Imaging research has also provided valuable knowledge in the understanding of the pathology of IIM. This review explores the latest advancements of these imaging modalities in IIM. RECENT FINDINGS: Recent advancements in imaging of IIM have seen a shift away from manual and qualitative analysis of the images. Quantitative MRI provides more objective, and potentially more sensitive characterization of fat infiltration and inflammation in muscles. In addition to B-mode ultrasound changes, shearwave elastography offers a new dimension to investigating IIM. PET/CT has the added advantage of including IIM-associated findings such as malignancies. SUMMARY: It is evident that MRI, ultrasound and PET/CT have important roles in myositis. Continued technological advancement and a quest for more sophisticated applications help drive innovation; this has especially been so of machine learning/deep learning using artificial intelligence and the developing promise of texture analysis.

Subclinical Systemic Sclerosis Primary Heart Involvement by Cardiovascular Magnetic Resonance Shows No Significant Interval Change.

OBJECTIVE: Subclinical systemic sclerosis (SSc) primary heart involvement is commonly described. Whether these findings progress over time is not clear. The study aimed to investigate cardiovascular magnetic resonance (CMR) interval change of subclinical SSc primary heart involvement. METHODS: Patients with SSc with no cardiovascular disease underwent two CMR scans that included T1 mapping and quantitative stress perfusion. The CMR change (mean difference) and association between CMR measures and clinical phenotype were assessed. The study had a prospective design. RESULTS: Thirty-one patients with SSc participated, with a median (interquartile range) follow-up of 33 (17-37) months (10 [32%] in the diffuse subset, 16 [52%] with interstitial lung disease [ILD], and 11 [29%] who were Scl-70+). Four of thirty-one patients had focal late gadolinium enhancement (LGE) at visit 1; one of four had an increase in LGE scar mass between visits. Two patients showed new focal LGE at visit 2. No change in other CMR indices was noted. The three patients with SSc with increased or new LGE at visit 2 had diffuse cutaneous SSc with ILD, and two were Scl-70+. A reduction in forced vital capacity and total lung capacity was associated with a reduction in left ventricular ejection fraction (ρ = 0.413, P = 0.021; ρ = 0.335, P = 0.07) and myocardial perfusion reserve (MPR) (ρ = 0.543, P = 0.007; ρ = 0.627, P = 0.002). An increase in the N-terminal pro-brain natriuretic peptide level was associated with a reduction in MPR (ρ = -0.448, P = 0.042). Patients on disease-modifying antirheumatic drugs (DMARDs) had an increase in native T1 (mean [SD] 1208 [65] vs. 1265 [56] milliseconds, P = 0.008). No other clinically meaningful CMR change in patients receiving DMARDs or vasodilators was noted. CONCLUSION: Serial CMR detects interval subclinical SSc primary heart involvement progression; however, this study suggests abnormalities remain largely stable with follow-up.

First pilot study of extracellular volume MRI measurement in peripheral muscle of systemic sclerosis patients suggests diffuse fibrosis.

OBJECTIVES: Peripheral muscle involvement in SSc may comprise myositis or a non-inflammatory myopathy. There is little understanding of the nature of SSc myopathy. This pilot study aimed to evaluate the presence of diffuse fibrosis in the peripheral muscle of patients with SSc by determining extracellular volume (ECV) MRI measurement. METHODS: SSc patients, with either suspected myopathy or no muscle involvement, and healthy controls (HCs) had native T1 and ECV MRI quantification of the thigh and creatine-kinase (CK) measured. Suspected myopathy was defined as current / history of minimally raised CK (>320; <600 IU/l) ± presence of clinical signs/symptoms (including proximal lower-limb muscle weakness and/or myalgia) ± a Manual Muscle Testing (MMT) 8 score of <5 in the thighs. RESULTS: Twelve SSc patients and 10 HCs were recruited. Of the 12 patients, 9 had limited cutaneous SSc, 4 had interstitial lung disease, and 7 had suspected myopathy. The higher skeletal muscle ECV was recorded for SSc patients compared with HCs [mean (s.d.) 23 (11)%, vs 11 (4)%, P = 0.04]. Peripheral muscle ECV was associated with CK (rho = 0.554, P = 0.061) and was higher in SSc patients with myopathy than in those with no myopathy [mean (s.d.) 28 (10) vs 15 (5), P = 0.023]. It was determined that an ECV of 22% best identified myopathy (with a sensitivity of 71% and a specificity of 80%). CONCLUSION: This hypothesis-generating study showed higher ECV in SSc patients compared with HCs, as well as association of ECV with suspected myopathy, suggesting the presence of diffuse fibrosis in the peripheral muscle of SSc patients. Further studies are needed to understand the nature of SSc myopathy.

Cardiovascular outcomes in systemic sclerosis with abnormal cardiovascular MRI and serum cardiac biomarkers.

OBJECTIVES: To explore the prognostic value of subclinical cardiovascular (CV) imaging measures and serum cardiac biomarkers in systemic sclerosis (SSc) for the development of CV outcomes of primary heart involvement (pHI). METHODS: Patients with SSc with no clinical SSc-pHI and no history of heart disease underwent cardiovascular magnetic resonance (CMR) imaging, and measurement of serum high-sensitivity-troponin I (hs-TnI) and N-terminal-pro-brain natriuretic peptide (NT-proBNP). Follow-up clinical and CV outcome data were recorded. CV outcomes were defined as myocarditis, arrhythmia and/or echocardiographic functional impairment including systolic dysfunction and/or diastolic dysfunction. RESULTS: Seventy-four patients with a median (IQR) age of 57 (49, 63) years, 32% diffuse cutaneous SSc, 39% interstitial lung disease, 30% Scl70+ were followed up for median (IQR) 22 (15, 54) months. Ten patients developed CV outcomes, comprising one patient with myocarditis and systolic dysfunction and nine arrhythmias: three non-sustained ventricular tachycardia and six supraventricular arrhythmias. The probability of CV outcomes was considerably higher in those with NT-proBNP >125 pg/mL versus normal NT-proBNP (X2=4.47, p=0.035). Trend for poorer time-to-event was noted in those with higher extracellular volume (ECV; indicating diffuse fibrosis) and hs-TnI levels versus those with normal values (X2=2.659, p=0.103; X2=2.530, p=0.112, respectively). In a predictive model, NT-proBNP >125 pg/mL associated with CV outcomes (OR=5.335, p=0.040), with a trend observed for ECV >29% (OR=4.347, p=0.073). CONCLUSION: These data indicate standard serum cardiac biomarkers (notably NT-proBNP) and CMR indices of myocardial fibrosis associate with adverse CV outcomes in SSc. This forms the basis to develop a prognostic model in larger, longitudinal studies.

Clinical associations with stage B heart failure in adults with type 2 diabetes.

BACKGROUND: There is a high prevalence of asymptomatic (American Heart Association Stage B) heart failure (SBHF) in people with type 2 diabetes (T2D). We aimed to identify associations between clinical characteristics and markers of SBHF in adults with T2D, which may allow therapeutic interventions prior to symptom onset. METHODS: Adults with T2D from a multi-ethnic population with no prevalent cardiovascular disease [n = 247, age 52 ± 12 years, glycated haemoglobin A1c (HbA1c) 7.4 ± 1.1% (57 ± 12 mmol/mol), duration of diabetes 61 (32, 120) months] underwent echocardiography and adenosine stress perfusion cardiovascular magnetic resonance imaging. Multivariable linear regression analyses were performed to identify independent associations between clinical characteristics and markers of SBHF. RESULTS: In a series of multivariable linear regression models containing age, sex, ethnicity, smoking history, number of glucose-lowering agents, systolic blood pressure (BP) duration of diabetes, body mass index (BMI), HbA1c, serum creatinine, and low-density lipoprotein (LDL)-cholesterol, independent associations with: left ventricular mass:volume were age (ß = 0.024), number of glucose-lowering agents (ß = 0.022) and systolic BP (ß = 0.027); global longitudinal strain were never smoking (ß = -1.196), systolic BP (ß = 0.328), and BMI (ß = -0.348); myocardial perfusion reserve were age (ß = -0.364) and male sex (ß = 0.458); and aortic distensibility were age (ß = -0.629) and systolic BP (ß = -0.348). HbA1c was not independently associated with any marker of SBHF. CONCLUSIONS: In asymptomatic adults with T2D, age, systolic BP, BMI, and smoking history, but not glycaemic control, are the major determinants of SBHF. Given BP and BMI are modifiable, these may be important targets to reduce the development of symptomatic heart failure.

Predictors of subclinical systemic sclerosis primary heart involvement characterised by microvasculopathy and myocardial fibrosis.

OBJECTIVES: SSc primary heart involvement (SSc-pHI) is a significant cause of mortality. We aimed to characterize and identify predictors of subclinical SSc-pHI using cardiovascular MRI. METHODS: A total of 83 SSc patients with no history of cardiovascular disease or pulmonary arterial hypertension and 44 healthy controls (HCs) underwent 3 Tesla contrast-enhanced cardiovascular MRI, including T1 mapping and quantitative stress perfusion. High-sensitivity troponin I and N-terminal pro-brain natriuretic peptide were also measured. RESULTS: Cardiovascular MRI revealed a lower myocardial perfusion reserve in the SSc patients compared with HCs {median (interquartile range (IQR)] 1.9 (1.6-2.4) vs 3 (2-3.6), P < 0.001}. Late gadolinium enhancement, indicating focal fibrosis, was observed in 17/83 patients but in none of the HCs, with significantly higher extracellular volume (ECV), suggestive of diffuse fibrosis, in SSc vs HC [mean (s.d.) 31 (4) vs 25 (2), P < 0.001]. Presence of late gadolinium enhancement and higher ECV was associated with skin score [odds ratio (OR) = 1.115, P = 0.048; R2 = 0.353, P = 0.004], and ECV and myocardial perfusion reserve was associated with the presence of digital ulcers at multivariate analysis (R2 = 0.353, P < 0.001; R2 = 0.238, P = 0.011). High-sensitivity troponin I was significantly higher in patients with late gadolinium enhancement, and N-terminal pro-brain natriuretic peptide was associated with ECV (P < 0.05). CONCLUSION: Subclinical SSc-pHI is characterized by myocardial microvasculopathy, diffuse and focal myocardial fibrosis but preserved myocardial contractile function. This subclinical phenotype of SSc-pHI was associated with high-sensitivity troponin I, N-terminal pro-brain natriuretic peptide, SSc disease severity and complicated peripheral vasculopathy. These data provide information regarding the underlying pathophysiological processes and provide a basis for identifying individuals at risk of SSc-pHI.

Muscle deterioration due to rheumatoid arthritis: assessment by quantitative MRI and strength testing.

OBJECTIVES: RA patients often present with low muscle mass and decreased strength. Quantitative MRI offers a non-invasive measurement of muscle status. This study assessed whether MRI-based measurements of T2, fat fraction, diffusion tensor imaging and muscle volume can detect differences between the thigh muscles of RA patients and healthy controls, and assessed the muscle phenotype of different disease stages. METHODS: Thirty-nine RA patients (13 'new RA'-newly diagnosed, treatment naïve, 13 'active RA'-persistent DAS28 >3.2 for >1 year, 13 'remission RA'-persistent DAS28 <2.6 for >1 year) and 13 age and gender directly matched healthy controls had an MRI scan of their dominant thigh. All participants had knee extension and flexion torque and grip strength measured. RESULTS: MRI T2 and fat fraction were higher in the three groups of RA patients compared with healthy controls in the thigh muscles. There were no clinically meaningful differences in the mean diffusivity. The muscle volume, handgrip strength, knee extension and flexion were lower in all three groups of RA patients compared with healthy controls. CONCLUSION: Quantitative MRI and muscle strength measurements can potentially detect differences within the muscles between RA patients and healthy controls. These differences may be seen in RA patients who are yet to start treatment, those with persistent active disease, and those who were in clinical remission. This suggests that the muscles in RA patients are affected in the early stages of the disease and that signs of muscle pathology and muscle weakness are still observed in clinical remission.

Novel Muscle Imaging in Inflammatory Rheumatic Diseases-A Focus on Ultrasound Shear Wave Elastography and Quantitative MRI.

In recent years, imaging has played an increasing role in the clinical management of patients with rheumatic diseases with respect to aiding diagnosis, guiding therapy and monitoring disease progression. These roles have been underpinned by research which has enhanced our understanding of disease pathogenesis and pathophysiology of rheumatology conditions, in addition to their key role in outcome measurement in clinical trials. However, compared to joints, imaging research of muscles is less established, despite the fact that muscle symptoms are very common and debilitating in many rheumatic diseases. Recently, it has been shown that even though patients with rheumatoid arthritis may achieve clinical remission, defined by asymptomatic joints, many remain affected by lingering constitutional systemic symptoms like fatigue, tiredness, weakness and myalgia, which may be attributed to changes in the muscles. Recent improvements in imaging technology, coupled with an increasing clinical interest, has started to ignite new interest in the area. This perspective discusses the rationale for using imaging, particularly ultrasound and MRI, for investigating muscle pathology involved in common inflammatory rheumatic diseases. The muscles associated with rheumatic diseases can be affected in many ways, including myositis-an inflammatory muscle condition, and myopathy secondary to medications, such as glucocorticoids. In addition to non-invasive visual assessment of muscles in these conditions, novel imaging techniques like shear wave elastography and quantitative MRI can provide further useful information regarding the physiological and biomechanical status of the muscle.

Cardiovascular Determinants of Aerobic Exercise Capacity in Adults With Type 2 Diabetes.

OBJECTIVE: To assess the relationship between subclinical cardiac dysfunction and aerobic exercise capacity (peak VO2) in adults with type 2 diabetes (T2D), a group at high risk of developing heart failure. RESEARCH DESIGN AND METHODS: Cross-sectional study. We prospectively enrolled a multiethnic cohort of asymptomatic adults with T2D and no history, signs, or symptoms of cardiovascular disease. Age-, sex-, and ethnicity-matched control subjects were recruited for comparison. Participants underwent bioanthropometric profiling, cardiopulmonary exercise testing, and cardiovascular magnetic resonance with adenosine stress perfusion imaging. Multivariable linear regression analysis was undertaken to identify independent associations between measures of cardiovascular structure and function and peak VO2. RESULTS: A total of 247 adults with T2D (aged 51.8 ± 11.9 years, 55% males, 37% black or south Asian ethnicity, HbA1c 7.4 ± 1.1% [57 ± 12 mmol/mol], and duration of diabetes 61 [32-120] months) and 78 control subjects were included. Subjects with T2D had increased concentric left ventricular remodeling, reduced myocardial perfusion reserve (MPR), and markedly lower aerobic exercise capacity (peak VO2 18.0 ± 6.6 vs. 27.8 ± 9.0 mL/kg/min; P < 0.001) compared with control subjects. In a multivariable linear regression model containing age, sex, ethnicity, smoking status, and systolic blood pressure, only MPR (ß = 0.822; P = 0.006) and left ventricular diastolic filling pressure (E/e') (ß = -0.388; P = 0.001) were independently associated with peak VO2 in subjects with T2D. CONCLUSIONS: In a multiethnic cohort of asymptomatic people with T2D, MPR and diastolic function are key determinants of aerobic exercise capacity, independent of age, sex, ethnicity, smoking status, or blood pressure.

Feasibility of MRI based extracellular volume fraction and partition coefficient measurements in thigh muscle.

OBJECTIVE: This study aimed to assess the feasibility of extracellular volume-fraction (ECV) measurement, and time to achieve contrast equilibrium (CE), in healthy muscles, and to determine whether in-flow and partial-volume errors in the femoral artery affect measurements, and if there are differences in the partition coefficient (λ) between muscles. METHODS: T1 was measured in the biceps femoris, vastus intermedius, femoral artery and aorta of 10 healthy participants. This was repeated alternately between the thigh and aorta for ≥25 min following a bolus of gadoterate meglumine. λ was calculated for each muscle/blood measurement. Time to CE was assessed semi-quantitatively. RESULTS: 8/10 participants achieved CE. Time to CE = 19±2 min (mean ± 95% confidence interval). Measured λ: biceps femoris/aorta = 0.210±0.034, vastus intermedius/aorta = 0.165±0.015, biceps femoris/femoral artery = 0.265±0.054, vastus intermedius/femoral artery = 0.211±0.026. There were significant differences in λ between the muscles when using the same vessel (p < 0.05), and between λ calculated in the same muscle when using different vessels (p < 0.05). CONCLUSION: ECV measurements in the thigh are clinically feasible. The use of the femoral artery for the blood measurement is associated with small but significant differences in λ. ECV measurements are sensitive to differences between muscles within the healthy thigh. ADVANCES IN KNOWLEDGE: This paper determines the time to contrast equilibrium in the healthy thigh and describes a method for measuring accurately ECV in skeletal muscle. This can aid in the diagnosis and understanding of inflammatory auto-immune diseases.

A randomized, open-label, active comparator trial assessing the effects of 26 weeks of liraglutide or sitagliptin on cardiovascular function in young obese adults with type 2 diabetes.

AIM: To compare the effects of a glucagon-like peptide-1 receptor agonist and a dipeptidyl peptidase-4 inhibitor on magnetic resonance imaging-derived measures of cardiovascular function. MATERIALS AND METHODS: In a prospective, randomized, open-label, blinded endpoint trial liraglutide (1.8 mg) and sitagliptin (100 mg) were compared in asymptomatic, non-insulin treated young (aged 18-50 years) adults with obesity and type 2 diabetes. The primary outcome was difference in circumferential peak early diastolic strain rate change (PEDSR), a biomarker of cardiac diastolic dysfunction 26 weeks after randomization. Secondary outcomes included other indices of cardiac structure and function, HbA1c and body weight. RESULTS: Seventy-six participants were randomized (54% female, mean ± SD age 44 ± 6 years, diabetes duration 4.4 years, body mass index 35.3 ± 6.1 kg m-2 ), of whom 65% had ≥1 cardiovascular risk factor. Sixty-one participants had primary outcome data available. There were no statistically significant between-group differences (intention-to-treat; mean [95% confidence interval]) in PEDSR change (-0.01 [-0.07, +0.06] s-1 ), left ventricular ejection fraction (-1.98 [-4.90, +0.94]%), left ventricular mass (+1.14 [-5.23, +7.50] g) or aortic distensibility (-0.35 [-0.98, +0.28] mmHg-1 × 10-3 ) after 26 weeks. Reductions in HbA1c (-4.57 [-9.10, -0.37] mmol mol-1 ) and body weight (-3.88 [-5.74, -2.01] kg) were greater with liraglutide. CONCLUSION: There were no differences in cardiovascular structure or function after short-term use of liraglutide and sitagliptin in younger adults with obesity and type 2 diabetes. Longer studies in patients with more severe cardiac dysfunction may be necessary before definitive conclusions can be made about putative pleiotropic properties of incretin-based therapies.

Effects of Low-Energy Diet or Exercise on Cardiovascular Function in Working-Age Adults With Type 2 Diabetes: A Prospective, Randomized, Open-Label, Blinded End Point Trial.

OBJECTIVE: To confirm the presence of subclinical cardiovascular dysfunction in working-age adults with type 2 diabetes (T2D) and determine whether this is improved by a low-energy meal replacement diet (MRP) or exercise training. RESEARCH DESIGN AND METHODS: This article reports on a prospective, randomized, open-label, blinded end point trial with nested case-control study. Asymptomatic younger adults with T2D were randomized 1:1:1 to a 12-week intervention of 1) routine care, 2) supervised aerobic exercise training, or 3) a low-energy (∼810 kcal/day) MRP. Participants underwent echocardiography, cardiopulmonary exercise testing, and cardiac magnetic resonance (CMR) at baseline and 12 weeks. The primary outcome was change in left ventricular (LV) peak early diastolic strain rate (PEDSR) as measured by CMR. Healthy volunteers were enrolled for baseline case-control comparison. RESULTS: Eighty-seven participants with T2D (age 51 ± 7 years, HbA1c 7.3 ± 1.1%) and 36 matched control participants were included. At baseline, those with T2D had evidence of diastolic dysfunction (PEDSR 1.01 ± 0.19 vs. 1.10 ± 0.16 s-1, P = 0.02) compared with control participants. Seventy-six participants with T2D completed the trial (30 routine care, 22 exercise, and 24 MRP). The MRP arm lost 13 kg in weight and had improved blood pressure, glycemia, 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 (ß = 0.132, P = 0.002) but did not improve with the MRP (ß = 0.016, P = 0.731). CONCLUSIONS: In asymptomatic working-age adults with T2D, exercise training improved diastolic function. Despite beneficial effects of weight loss on glycemic control, concentric LV remodeling, and aortic stiffness, a low-energy MRP did not improve diastolic function.

Normal values and test-retest variability of stimulated-echo diffusion tensor imaging and fat fraction measurements in the muscle.

OBJECTIVES: To assess the test-retest variability of both diffusion parameters and fat fraction (FF) estimates in normal muscle, and to assess differences in normal values between muscles in the thigh. METHODS: 29 healthy volunteers (mean age 37 years, range 20-60 years, 17/29 males) completed the study. Magnetic resonance images of the mid-thigh were acquired using a stimulated echo acquisition mode-echoplanar imaging (STEAM-EPI) imaging sequence, to assess diffusion, and 2-point Dixon imaging, to assess FF. Imaging was repeated in 19 participants after a 30 min interval in order to assess test-retest variability of the measurements. RESULTS: Intraclass correlation coefficients (ICCs) for test-retest variability were 0.99 [95% confidence interval, (CI): 0.98, 1] for FF, 0.94 (95% CI: 0.84, 0.97) for mean diffusivity and 0.89 (95% CI: 0.74, 0.96) for fractional anisotropy (FA). FF was higher in the hamstrings than the quadriceps by a mean difference of 1.81% (95% CI:1.63, 2.00)%, p < 0.001. Mean diffusivity was significantly lower in the hamstrings than the quadriceps (0.26 (0.13, 0.39) x10-3 mm2s-1, p < 0.001) whereas fractional anisotropy was significantly higher in the hamstrings relative to the quadriceps with a mean difference of 0.063 (0.05, 0.07), p < 0.001. CONCLUSIONS: This study has shown excellent test-retest, variability in MR-based FF and diffusion measurements and demonstrated significant differences in these measures between hamstrings and quadriceps in the healthy thigh. ADVANCES IN KNOWLEDGE: Test-retest variability is excellent for STEAM-EPI diffusion and 2-point Dixon-based FF measurements in the healthy muscle. Inter- and intraobserver variability were excellent for region of interest placement for STEAM-EPI diffusion and 2-point Dixon-based FF measurements in the healthy muscle. There are significant differences in FF and diffusion measurements between the hamstrings and quadriceps in the normal muscle.

Incidental significant arrhythmia in scleroderma associates with cardiac magnetic resonance measure of fibrosis and hs-TnI and NT-proBNP.

OBJECTIVES: To screen for significant arrhythmias with an implantable loop recorder (ILR) in patients with SSc and no known cardiovascular disease, and identify associated disease phenotype, blood and cardiovascular magnetic resonance (CMR) biomarkers. METHODS: Twenty patients with SSc with no history of primary SSc heart disease, traditional cardiovascular disease, diabetes or maximum one traditional cardiovascular risk factor underwent clinical assessment, contrast-enhanced CMR and ILR insertion. RESULTS: ILR data were available for 19 patients: 63% female, mean (s.d.) age of 53 (12) years, 32% diffuse SSc. Eight patients had significant arrhythmias over 3 years: one complete heart block, two non-sustained ventricular tachycardia [all three dcSSc, two anti-topoisomerase antibodies (Scl70) positive, three interstitial lung disease and two previous digital ulceration] and five atrial arrhythmias of which four were with limited SSc. These required interventions with one permanent pacemaker implantation, four anti-arrhythmic pharmacotherapy, one anticoagulation.Patients with significant arrhythmia had higher baseline high-sensitivity troponin I and N-terminal pro-brain natriuretic peptide [mean difference (95% CI) 117 (-11, 245) and 92 (-30, 215) ng/l, respectively], and CMR-extracellular volume [mean (s.d.) 32 (2) vs 29 (4)%]. Late gadolinium enhancement was observed in five patients, only one with significant arrhythmia. CONCLUSION: This first ILR study identified potentially life-threatening arrhythmias in asymptomatic SSc patients attributable to a primary SSc heart disease. Disease phenotype, CMR-extracellular volume (indicating diffuse fibrosis) and cardiac biomarkers may identify at-risk patients that would benefit from ILR screening. Future studies can inform a risk model and provide insights into SSc-associated arrhythmia pathogenesis.

Quantitative Myocardial Perfusion Imaging Versus Visual Analysis in Diagnosing Myocardial Ischemia: A CE-MARC Substudy.

OBJECTIVES: This study sought to compare the diagnostic accuracy of visual and quantitative analyses of myocardial perfusion cardiovascular magnetic resonance against a reference standard of quantitative coronary angiography. BACKGROUND: Visual analysis of perfusion cardiovascular magnetic resonance studies for assessing myocardial perfusion has been shown to have high diagnostic accuracy for coronary artery disease. However, only a few small studies have assessed the diagnostic accuracy of quantitative myocardial perfusion. METHODS: This retrospective study included 128 patients randomly selected from the CE-MARC (Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease) study population such that the distribution of risk factors and disease status was proportionate to the full population. Visual analysis results of cardiovascular magnetic resonance perfusion images, by consensus of 2 expert readers, were taken from the original study reports. Quantitative myocardial blood flow estimates were obtained using Fermi-constrained deconvolution. The reference standard for myocardial ischemia was a quantitative coronary x-ray angiogram stenosis severity of ≥70% diameter in any coronary artery of >2 mm diameter, or ≥50% in the left main stem. Diagnostic performance was calculated using receiver-operating characteristic curve analysis. RESULTS: The area under the curve for visual analysis was 0.88 (95% confidence interval: 0.81 to 0.95) with a sensitivity of 81.0% (95% confidence interval: 69.1% to 92.8%) and specificity of 86.0% (95% confidence interval: 78.7% to 93.4%). For quantitative stress myocardial blood flow the area under the curve was 0.89 (95% confidence interval: 0.83 to 0.96) with a sensitivity of 87.5% (95% confidence interval: 77.3% to 97.7%) and specificity of 84.5% (95% confidence interval: 76.8% to 92.3%). There was no statistically significant difference between the diagnostic performance of quantitative and visual analyses (p = 0.72). Incorporating rest myocardial blood flow values to generate a myocardial perfusion reserve did not significantly increase the quantitative analysis area under the curve (p = 0.79). CONCLUSIONS: Quantitative perfusion has a high diagnostic accuracy for detecting coronary artery disease but is not superior to visual analysis. The incorporation of rest perfusion imaging does not improve diagnostic accuracy in quantitative perfusion analysis.

Patient-specific coronary blood supply territories for quantitative perfusion analysis.

Myocardial perfusion imaging, coupled with quantitative perfusion analysis, provides an important diagnostic tool for the identification of ischaemic heart disease caused by coronary stenoses. The accurate mapping between coronary anatomy and under-perfused areas of the myocardium is important for diagnosis and treatment. However, in the absence of the actual coronary anatomy during the reporting of perfusion images, areas of ischaemia are allocated to a coronary territory based on a population-derived 17-segment (American Heart Association) AHA model of coronary blood supply. This work presents a solution for the fusion of 2D Magnetic Resonance (MR) myocardial perfusion images and 3D MR angiography data with the aim to improve the detection of ischaemic heart disease. The key contribution of this work is a novel method for the mediated spatiotemporal registration of perfusion and angiography data and a novel method for the calculation of patient-specific coronary supply territories. The registration method uses 4D cardiac MR cine series spanning the complete cardiac cycle in order to overcome the under-constrained nature of non-rigid slice-to-volume perfusion-to-angiography registration. This is achieved by separating out the deformable registration problem and solving it through phase-to-phase registration of the cine series. The use of patient-specific blood supply territories in quantitative perfusion analysis (instead of the population-based model of coronary blood supply) has the potential of increasing the accuracy of perfusion analysis. Quantitative perfusion analysis diagnostic accuracy evaluation with patient-specific territories against the AHA model demonstrates the value of the mediated spatiotemporal registration in the context of ischaemic heart disease diagnosis.