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Systemic amyloidosis is a serious multiorgan disease with reduced life expectancy, irrespective of type. The impact of magnetic resonance imaging (MRI) in managing this condition has been immense. The last decade in particular has seen a surge of interest in the assessment and evaluation of the heart in patients with systemic amyloidosis by cardiovascular magnetic resonance imaging (CMR), with approximately 85% of all publications on this subject arising in the last 10 years. This has been largely driven by the creation of new sequences and their subsequent modernisation and technical development, thereby rendering previously prohibitive methods clinically more relevant and applicable. In turn, this has led to an increased awareness and recognition of the disease. This review demonstrates how MRI has become a pivotal diagnostic tool in the assessment of cardiac amyloidosis over the last 2 decades, with the ability to track disease and predict mortality. Several different pathognomonic patterns of late gadolinium enhancement (LGE) are now recognised and are able to prognosticate. T1 mapping and extracellular volume (ECV) techniques have resulted in even earlier disease detection before LGE is even visible and along with T2 mapping, provide new insights into biology. As newer therapies also evolve and become available, the need for accurate tracking of cardiac disease response to treatment carries increasing importance. All these are examined in this review, mainly focussing on light-chain (AL) and transthyretin (ATTR) amyloidosis.

A 20-year-old Congolese woman presented with presyncope, dyspnea, and anasarca. Past medical history was unremarkable. Echocardiography revealed a rare combination of giant right atrium (RA), a dilated and hypertrophied right ventricle, subvalvular pulmonary stenosis (subPS), severe tricuspid regurgitation (TR), pericardial effusion and what appeared to be a spontaneously closed ventricular septal defect (VSD). Cardiac Magnetic Resonance and Cardiac Computed Tomography confirmed the findings excluding the presence of intra-cardiac and extra-cardiac shunt and other associated congenital anomalies. The patient underwent subPS resection, right atrioplasty, and tricuspid annuloplasty. Multimodality approach facilitated the detection of the abnormalities and provided clarity when determining the optimal surgical strategy.

To investigate cardiac magnetic resonance (MR) imaging measurements of extracellular volume (ECV) and total cell volume in immunoglobulin light-chain amyloidosis (AL) and transthyretin amyloidosis (ATTR) in order to evaluate the amyloid and myocyte volumes.All ethics were approved, and participants provided written informed consent. Of the 257 subjects who were recruited, 92 had AL (mean age, 62 years ± 10), 44 had mutant ATTR (mean age, 68 years ± 10), and 66 had wild-type ATTR (mean age, 75 years ± 7). In addition, eight healthy subjects with ATTR mutations (mean age, 47 years ± 6) and 47 healthy volunteers (mean age, 45 years ± 15) participated. All participants underwent equilibrium contrast material-enhanced cardiac MR imaging. ECV and total cell volume were measured in the heart. T test, χ(2), and one-way analysis of variance with posthoc Bonferroni correction were used.Both the left ventricular indexed mass and ECV were elevated in patients with amyloidosis. For left ventricular indexed mass, mean AL was 107 g/m(2) ± 30; mean mutant ATTR was 137 g/m(2) ± 29; and mean wild-type ATTR was 133 g/m(2) ± 27 versus 65 g/m(2) ± 15 in healthy subjects (P.0001 for all measures). For ECV, mean AL was 0.54 ± 0.07, mean mutant ATTR was 0.60 ± 0.07, and mean wild-type ATTR was 0.57 ± 0.06 versus 0.27 ± 0.03 in healthy subjects (P.0001 for all measures). Patients with ATTR had a higher total cell volume than did healthy subjects (mean, 53 mL/m(2) ± 12 vs 45 mL/m(2) ± 11; P = .001), but in patients with AL, total cell volume was normal (mean, 47 mL/m(2) ± 17 vs 45 mL/m(2) ± 11; P.99). The result is that, in patients with AL, all of the increase in left ventricular indexed mass is extracellular volume, whereas in patients with ATTR, the increase is extracellular, with an additional 18% increase in the intracellular space.Quantification of ECV measures cardiac amyloid deposition in both types of amyloidosis and shows that amyloid deposition is more extensive in patients with ATTR than in those with AL; however, ATTR is associated with higher cell volume, which suggests concomitant cell hypertrophy.

Purpose To explore the use and reproducibility of magnetic resonance-derived myocardial T1 mapping in patients with iron overload. Materials and Methods The research received ethics committee approval and all patients provided written informed consent. This was a prospective study of 88 patients and 67 healthy volunteers. Thirty-five patients underwent repeat scanning for reproducibility. T1 mapping used the shortened modified Look–Locker inversion recovery sequence (ShMOLLI) with a second, confirmatory MOLLI sequence in the reproducibility group. T2* was performed using a commercially available sequence. The analysis of the T2* interstudy reproducibility data was performed by two different research groups using two different methods. Results Myocardial T1 was lower in patients than healthy volunteers (836 ± 138 msec vs. 968 ± 32 msec, P

Objectives The aim of this study was to determine the accuracy of the contrast “bolus only” T1 mapping cardiac magnetic resonance (CMR) technique for measuring myocardial extracellular volume fraction (ECV). Background Myocardial ECV can be measured with T1 mapping before and after contrast agent if the contrast agent distribution between blood/myocardium is at equilibrium. Equilibrium distribution can be achieved with a primed contrast infusion (equilibrium contrast-CMR [EQ-CMR]) or might be approximated by the dynamic equilibration achieved by delayed post-bolus measurement. This bolus only approach is highly attractive, but currently limited data support its use. We compared the bolus only technique with 2 independent standards: collagen volume fraction (CVF) from myocardial biopsy in aortic stenosis (AS); and the infusion technique in 5 representative conditions. Methods One hundred forty-seven subjects were studied: healthy volunteers (n = 50); hypertrophic cardiomyopathy (n = 25); severe AS (n = 22); amyloid (n = 20); and chronic myocardial infarction (n = 30). Bolus only (at 15 min) and infusion ECV measurements were performed and compared. In 18 subjects with severe AS the results were compared with histological CVF. Results The ECV by both techniques correlated with histological CVF (n = 18, r 2 = 0.69, p 2 = 0.71, p 2 = 0.97). However, in diseases of high ECV (amyloid, hypertrophic cardiomyopathy late gadolinium enhancement, and infarction), Bland-Altman analysis indicates the bolus only technique has a consistent and increasing offset, giving a higher value for ECVs above 0.4 (mean difference ± limit of agreement for ECV 0.4 = 0.040 ± 0.075, p Conclusions Bolus only, T1 mapping-derived ECV measurement is sufficient for ECV measurement across a range of cardiac diseases, and this approach is histologically validated in AS. However, when ECV is >0.4, the bolus only technique consistently measures ECV higher compared with infusion.

Background— Anderson-Fabry disease (AFD) is a rare but underdiagnosed intracellular lipid disorder that can cause left ventricular hypertrophy (LVH). Lipid is known to shorten the magnetic resonance imaging parameter T1. We hypothesized that noncontrast T1 mapping by cardiovascular magnetic resonance would provide a novel and useful measure in this disease with potential to detect early cardiac involvement and distinguish AFD LVH from other causes. Methods and Results— Two hundred twenty-seven subjects were studied: patients with AFD (n=44; 55% with LVH), healthy volunteers (n=67; 0% with LVH), patients with hypertension (n=41; 24% with LVH), patients with hypertrophic cardiomyopathy (n=34; 100% with LVH), those with severe aortic stenosis (n=21; 81% with LVH), and patients with definite amyloid light-chain (AL) cardiac amyloidosis (n=20; 100% with LVH). T1 mapping was performed using the shortened modified Look-Locker inversion sequence on a 1.5-T magnet before gadolinium administration with primary results derived from the basal and midseptum. Compared with health volunteers, septal T1 was lower in AFD and higher in other diseases (AFD versus healthy volunteers versus other patients, 882±47, 968±32, 1018±74 milliseconds; P r =−0.51; P =0.0004) and was abnormal in 40% of subjects who did not have LVH. Segmentally, AFD showed pseudonormalization or elevation of T1 in the left ventricular inferolateral wall, correlating with the presence or absence of late gadolinium enhancement (1001±82 versus 891±38 milliseconds; P Conclusions— Noncontrast T1 mapping shows potential as a unique and powerful measurement in the imaging assessment of LVH and AFD.

We thank Aquaro, Cohen, and colleagues for their interest in our article.1 Cardiac involvement is a chief driver of prognosis in systemic amyloidosis, and the stratification of patients is essential for prognosis and choosing management strategies. Cardiovascular magnetic resonance with late gadolinium enhancement has good diagnostic accuracy for cardiac amyloidosis, but its prognostic impact was uncertain.2–6 This study confirms incremental prognostic information after adjusting for known prognosis factors. We note the comments of Aquaro and colleagues regarding cardiac biopsy, but point out that microscopic histological analyses of these tiny samples is not only open to sampling error, but, crucially, the presence of amyloid in heart muscle is not actually proof of cardiac amyloidosis. It is essential to make the distinction between the presence of amyloid deposits and the clinical syndromes of amyloidosis. Amyloid deposits occur widely throughout the tissues in patients with systemic amyloidosis, often without any clinical consequences, providing the basis for rectal, salivary gland, skin, and fat biopsies to support diagnosis. It is likely …

About 4% of African Americans possess the isoleucine 122 (V122I) variant of transthyretin, associated with cardiac amyloidosis beyond ages of 55 to 60 years. Transthyretin amyloidosis associated with variant V122I (ATTR V122I) is likely to be an important cause of heart failure in Afro-Caribbean populations, but the high prevalence of left ventricular hypertrophy (LVH) and lack of awareness of this genetic disorder pose diagnostic hurdles. We report the electrocardiographic (ECG) features of ATTR V122I in the largest clinical series to date.Patients with ATTR V122I were identified in collaboration with the UK National Amyloidosis Centre. The ECG at presentation was assessed for cardiac rhythm, axis, and voltage complex size.We include 64 patients with ATTR V122I, with a median age of 74 years (range, 57-88 years). Normal or increased ECG voltage was present in 44.3% of patients, and overall 25% met the criteria for LVH. A significant negative correlation between voltage complex size and duration of illness was seen (P.05). First-degree heart block was evident in 56% of patients in sinus rhythm. During follow-up (n = 17; median, 28 months), 50% of patients with initial first-degree heart block required pacing.Electrocardiographic voltages meet the criteria for LVH in one quarter of patients with ATTR V122I cardiac amyloidosis. The widely held belief that cardiac amyloidosis is associated with low-voltage complexes is likely to contribute to underdiagnosis of ATTR V122I. First-degree heart block is common at diagnosis and identifies patients at high risk for subsequent pacing requirement.

Supplemental Digital Content is available in the text., Background— The prognosis and treatment of the 2 main types of cardiac amyloidosis, immunoglobulin light chain (AL) and transthyretin (ATTR) amyloidosis, are substantially influenced by cardiac involvement. Cardiovascular magnetic resonance with late gadolinium enhancement (LGE) is a reference standard for the diagnosis of cardiac amyloidosis, but its potential for stratifying risk is unknown. Methods and Results— Two hundred fifty prospectively recruited subjects, 122 patients with ATTR amyloid, 9 asymptomatic mutation carriers, and 119 patients with AL amyloidosis, underwent LGE cardiovascular magnetic resonance. Subjects were followed up for a mean of 24±13 months. LGE was performed with phase-sensitive inversion recovery (PSIR) and without (magnitude only). These were compared with extracellular volume measured with T1 mapping. PSIR was superior to magnitude-only inversion recovery LGE because PSIR always nulled the tissue (blood or myocardium) with the longest T1 (least gadolinium). LGE was classified into 3 patterns: none, subendocardial, and transmural, which were associated with increasing amyloid burden as defined by extracellular volume (P

Background Diffuse myocardial fibrosis (DMF) is important in cardiovascular disease, however until recently could only be assessed by invasive biopsy. We hypothesised that DMF measured by T1 mapping is elevated in isolated systemic hypertension. Methods In a study of well-controlled hypertensive patients from a specialist tertiary centre, 46 hypertensive patients (median age 56, range 21 to 78, 52 % male) and 50 healthy volunteers (median age 45, range 28 to 69, 52 % male) underwent clinical CMR at 1.5 T with T1 mapping (ShMOLLI) using the equilibrium contrast technique for extracellular volume (ECV) quantification. Patients underwent 24-hours Automated Blood Pressure Monitoring (ABPM), echocardiographic assessment of diastolic function, aortic stiffness assessment and measurement of NT-pro-BNP and collagen biomarkers. Results Late gadolinium enhancement (LGE) revealed significant unexpected underlying pathology in 6 out of 46 patients (13 %; myocardial infarction n = 3; hypertrophic cardiomyopathy (HCM) n = 3); these were subsequently excluded. Limited, non-ischaemic LGE patterns were seen in 11 out of the remaining 40 (28 %) patients. Hypertensives on therapy (mean 2.2 agents) had a mean ABPM of 152/88 mmHg, but only 35 % (14/40) had left ventricular hypertrophy (LVH; LV mass male > 90 g/m2; female > 78 g/m2). Native myocardial T1 was similar in hypertensives and controls (955 ± 30 ms versus 965 ± 38 ms, p = 0.16). The difference in ECV did not reach significance (0.26 ± 0.02 versus 0.27 ± 0.03, p = 0.06). In the subset with LVH, the ECV was significantly higher (0.28 ± 0.03 versus 0.26 ± 0.02, p

Objectives The aims of the study were to explore the ability of native myocardial T1 mapping by cardiac magnetic resonance to: 1) detect cardiac involvement in patients with transthyretin amyloidosis (ATTR amyloidosis); 2) track the cardiac amyloid burden; and 3) detect early disease. Background ATTR amyloidosis is an underdiagnosed cause of heart failure, with no truly quantitative test. In cardiac immunoglobulin light-chain amyloidosis (AL amyloidosis), T1 has high diagnostic accuracy and tracks disease. Here, the diagnostic role of native T1 mapping in the other key type of cardiac amyloid, ATTR amyloidosis, is assessed. Methods A total of 3 groups were studied: ATTR amyloid patients (n = 85; 70 males, age 73 ± 10 years); healthy individuals with transthyretin mutations in whom standard cardiac investigations were normal (n = 8; 3 males, age 47 ± 6 years); and AL amyloid patients (n = 79; 55 males, age 62 ± 10 years). These were compared with 52 healthy volunteers and 46 patients with hypertrophic cardiomyopathy (HCM). All underwent T1 mapping (shortened modified look-locker inversion recovery); ATTR patients and mutation carriers also underwent cardiac 3,3-diphosphono-1,2- propanodicarboxylicacid (DPD) scintigraphy. Results T1 was elevated in ATTR patients compared with HCM and normal subjects (1,097 ± 43 ms vs. 1,026 ± 64 ms vs. 967 ± 34 ms, respectively; both p < 0.0001). In established cardiac ATTR amyloidosis, T1 elevation was not as high as in AL amyloidosis (AL 1,130 ± 68 ms; p = 0.01). Diagnostic performance was similar for AL and ATTR amyloid (vs. HCM: AL area under the curve 0.84 [95% confidence interval: 0.76 to 0.92]; ATTR area under the curve 0.85 [95% confidence interval: 0.77 to 0.92]; p < 0.0001). T1 tracked cardiac amyloid burden as determined semiquantitatively by DPD scintigraphy (p < 0.0001). T1 was not elevated in mutation carriers (952 ± 35 ms) but was in isolated DPD grade 1 (n = 9, 1,037 ± 60 ms; p = 0.001). Conclusions Native myocardial T1 mapping detects cardiac ATTR amyloid with similar diagnostic performance and disease tracking to AL amyloid, but with lower maximal T1 elevation, and appears to be an early disease marker.

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To investigate equilibrium contrast material-enhanced magnetic resonance (MR) imaging measurement of extracellular volume (ECV) fraction within healthy abdominal tissues and to test the hypotheses that tissue ECV in systemic amyloid light-chain (AL) amyloidosis is greater than in healthy patients and show that this increase correlates with organ amyloid burden.A local ethics committee approved the study and all patients gave written informed consent. Forty healthy volunteers (18 men, 22 women; median age, 43 years; age range, 24-88 years) and 67 patients with AL amyloidosis (43 men, 24 women; median age, 65 years; age range, 38-81 years) underwent equilibrium MR imaging of the upper abdomen. ECV was measured in the liver, spleen, and paravertebral muscle. Patients with amyloidosis also underwent serum amyloid P (SAP) component scintigraphy so that specific organ involvement by amyloid could be scored. Variation in ECV between tissues was assessed by using a Friedman Test. Tissue ECV in healthy and amyloidosis groups were compared by using a Mann-Whitney U test. Spearman correlation was used to test for an association between the organ SAP score and ECV.ECV measured at equilibrium MR imaging varied significantly between organs in healthy volunteers (χ(2) = 31.0; P.001). ECV was highest in the spleen (0.34), followed by liver (0.29) and muscle (0.09). ECVs measured within the spleen (0.39; P.001), liver (0.31; P = .005), and muscle (0.16; P.001) were significantly higher in patients with amyloidosis than in healthy control subjects. ECV measured in the liver and spleen showed increasing organ amyloid burden assessed at SAP scintigraphy (liver, rs = 0.54; spleen, rs = 0.57).Equilibrium MR imaging can be used to define ECV within healthy tissues. ECV is increased in amyloidosis compared with healthy tissues, and this increase correlates with rising tissue amyloid burden.

Background Cardiac amyloidosis is a fatal disease whose prognosis and treatment rely on identification of the amyloid type. In our aging population transthyretin amyloidosis ( ATTR wt) is common and must be differentiated from other amyloid types. We report the clinical presentation, natural history, and prognostic features of ATTR wt compared with cardiac‐isolated AL amyloidosis and calculate the probability of disease diagnosis of ATTR wt from baseline factors. Methods and Results All patients with biopsy‐proven ATTR wt (102 cases) and isolated cardiac AL (36 cases) seen from 2002 to 2011 at the UK National Amyloidosis Center were included. Median survival from the onset of symptoms was 6.07 years in the ATTR wt group and 1.7 years in the AL group. Positive troponin, a pacemaker, and increasing New York Heart Association (NYHA) class were associated with worse survival in ATTR wt patients on univariate analysis. All patients with isolated cardiac AL and 24.1% of patients with ATTR wt had evidence of a plasma cell dyscrasia. Older age and lower N ‐terminal pro‐ B ‐type natriuretic peptide ( NT pro‐ BNP ) were factors significantly associated with ATTR wt. Patients aged 70 years and younger with an NT pro‐ BNP ATTR wt, as were patients older than 70 years with an NT pro‐ BNP Conclusions Factors at baseline associated with a worse outcome in ATTR wt are positive troponin T, a pacemaker, and NYHA class IV symptoms. The age of the patient at diagnosis and NT pro‐ BNP level can aid in distinguishing ATTR wt from AL amyloidosis.

Methods Ninety-five healthy volunteers, 45 patients with AndersonFabry disease (AFD), 48 with hypertension (HT), 65 with hypertrophic cardiomyopathy (HCM), 62 with severe aortic stenosis (AS), 85 with systemic amyloidosis (AMY) were enrolled. Longitudinal and transversal strain was calculated from 3 long-axis cine views, circumferential and radial strain from 3 short-axis cine images using a dedicated software (Tomtec Feature Tracking). Fourteen healthy volunteers were scanned twice, and inter-study, inter-observer, intra-observer intraclass correlation coefficients ranged between 0.36 and 0.77. Forty AS patients underwent a second scan six months after aortic valve replacement.

Methods ECV measurement was by EQ-CMR. The T1 mapping sequence was ShMOLLI. The contrast agent was Gadoterate meglumine (Dotarem) at 0.1mmol/Kg (bolus) plus infusion at 15 minutes at 0.0011 mmol/kg/min. CMR was at 1.5T (Siemens Avanto). ECV was measured in 43 well-controlled hypertensive patients from a specialist tertiary centre (median age 56, range 21 to 78, 55% male) and 50 healthy volunteers (median age 47, range 28 to 69, 58% male). ECV was calculated by ECV = (1-hematocrit) x (1/T1) myo ÷ (1/T1)blood.

Background Systemic AL Amyloidosis causes multiorgan dysfunction through interstitial expansion. We measured the extracellular volume fraction (ECV) in the : heart, liver, spleen and skeletal muscle in healthy volunteers and patients with Systemic Amyloidosis to test the hypotheses that (1) tissue ECV is greater in systemic AL Amyloidosis than in health and (2) ECV tracks organ amyloid burden. Methods Healthy volunteers (n=70; 35 male; 35 female; median age 46 years) and patients with systemic AL Amyloidosis (n=56; 36 male; 20 female; median age 62 years), with clinical indications for CMR scanning, additionally underwent multi-organ ECV measurement. Technical details were: gadoteric acid, 0.1mmol/Kg plus infusion, multibreathhold T1 measurement and equilibrium imaging of heart, liver spleen and biceps muscle at 1.5T (Siemens Avanto). Amyloidosis patients also underwent serum amyloid P component (SAP) scintigraphy to score liver and spleen involvement by amyloid. Results ECV of the heart, liver, spleen and muscle was significantly elevated in patients with amyloidosis (0.40, 0.33, 0.42 and 0.12 respectively) compared to healthy controls (0.25, 0.30, 0.34 and 0.09 respectively) (P

Background— Cardiac involvement predicts outcome in systemic AL amyloidosis and influences therapeutic options. Current methods of cardiac assessment do not quantify myocardial amyloid burden. We used equilibrium contrast cardiovascular magnetic resonance (EQ-CMR) to quantify the cardiac interstitial compartment, measured as myocardial extracellular volume (ECV) fraction, hypothesizing it would reflect amyloid burden. Methods and Results— Sixty patients with systemic AL amyloidosis (65% men, median age 65 years) underwent conventional clinical cardiovascular magnetic resonance, including late enhancement, equilibrium contrast cardiovascular magnetic resonance, and clinical cardiac evaluation, including ECG, echocardiography, assays of N-terminal pro-brain natriuretic peptide and Troponin T, and functional assessment comprising the 6-minute walk test in ambulant individuals. Cardiac involvement in the amyloidosis patients was categorized as definite, probable, or none, suspected by conventional criteria. Findings were compared with 82 healthy controls. Mean ECV was significantly greater in patients than healthy controls (0.25 versus 0.40, P P R =0.56, P R =0.69, P R =0.53, P =0.006). ECV was associated with smaller QRS voltages ( R =0.57, P R =0.36, P =0.03). Conclusions— Myocardial ECV measurement has potential to become the first noninvasive test to quantify cardiac amyloid burden.

Background Diffuse myocardial fibrosis (DMF) is an important factor in cardiac disease, but until recently could only be accurately assessed with biopsy. We hypothesised that DMF measured by Equilibrium contrast CMR (EQ-CMR) is elevated in cardiac pressure overload (hypertension and aortic stenosis), that the degree of DMF will track the clinical severity of pressure overload and cardiac effects, and as such DMF may be a key biomarker in assessing the cardiac effects of pressure overload.

Background Myocardial ECV can be measured using T1 mapping before and after contrast if the contrast agent distribution between blood:myocardial is at equilibrium. Equilibrium distribution can be achieved with a primed contrast infusion (EQ-CMR), or may be approximated by the dynamic equilibration achieved by delayed post bolus measurement. This bolus only approach is highly attractive but currently limited data support its use. We compared the bolus only technique with two gold standards: collagen volume fraction (CVF) from myocardial biopsy in aortic stenosis (AS), and the infusion technique in five representative conditions.

Systemic amyloidosis is a relatively rare multisystem disease caused by the deposition of misfolded protein in various tissues and organs. It may present to almost any specialty, and diagnosis is frequently delayed.[1][1] Cardiac involvement is a leading cause of morbidity and mortality, especially

Background Multi-organ disease with cardiac involvement carries a very poor prognosis in Systemic AL Amyloidosis. The risk of nephrogenic systemic fibrosis is a significant obstacle in assessing cardiac status using CMR in patients with systemic AL amyloidosis who have advanced renal failure. Measurement of myocardial T1 values has been limited until now, due to long breathhold times. We have developed a robust and clinically applicable technique for diagnosing cardiac amyloidosis by measuring absolute myocardial T1 values using the single breath hold, Shortened Modified Look-Locker Inversion Recovery (ShMOLLI) sequence without gadolinium administration.

In this study we have compared the multi flip angle (MFA) FLASH T1 mapping technique to shortened look locker inversion recovery (ShMOLLI) for assessment of pre and post contrast T1 for equilibium contrast CMR (EQ-CMR) and also potential pseudoequilibrium post bolus. Good agreement was found in the volume of distribution, Vd(m), between both techniques and at equilibirum.

Background Myocardial extracellular volume (ECV) is elevated in fibrosis or infiltration and can be quantified by measuring the haematocrit with pre and post contrast T1 at sufficient contrast equilibrium. Equilibrium CMR (EQ-CMR), using a bolus-infusion protocol, has been shown to provide robust measurements of ECV using a multibreath-hold T1 pulse sequence. Newer, faster sequences for T1 mapping promise whole heart coverage and improved clinical utility, but have not been validated. Methods Multibreathhold T1 quantification with heart rate correction and single breath-hold T1 mapping using Shortened Modified Look-Locker Inversion recovery (ShMOLLI) were used in equilibrium contrast CMR to generate ECV values and compared in 3 ways. Firstly, both techniques were compared in a spectrum of disease with variable ECV expansion (n=100, 50 healthy volunteers, 12 patients with hypertrophic cardiomyopathy, 18 with severe aortic stenosis, 20 with amyloid). Secondly, both techniques were correlated to human histological collagen volume fraction (CVF%, n=18, severe aortic stenosis biopsies). Thirdly, an assessment of test:retest reproducibility of the 2 CMR techniques was performed 1 week apart in individuals with widely different ECVs (n=10 healthy volunteers, n=7 amyloid patients). Results More patients were able to perform ShMOLLI than the multibreath-hold technique (6% unable to breath-hold). ECV calculated by multibreath-hold T1 and ShMOLLI showed strong correlation (r2=0.892), little bias (bias -2.2%, 95%CI -8.9% to 4.6%) and good agreement (ICC 0.922, range 0.802 to 0.961, p2= 0.589) but better by ShMOLLI ECV (r2= 0.685). Inter-study reproducibility demonstrated that ShMOLLI ECV trended towards greater reproducibility than the multibreath-hold ECV, although this did not reach statistical significance (95%CI -4.9% to 5.4% versus 95%CI -6.4% to 7.3% respectively, p=0.21). Conclusions ECV quantification by single breath-hold ShMOLLI T1 mapping can measure ECV by EQ-CMR across the spectrum of interstitial expansion. It is procedurally better tolerated, slightly more reproducible and better correlates with histology compared to the older multibreath-hold FLASH techniques.

To measure and assess the significance of myocardial extracellular volume (ECV), determined non-invasively by equilibrium contrast cardiovascular magnetic resonance, as a clinical biomarker in health and a number of cardiac diseases of varying pathophysiology.Prospective study.Tertiary referral cardiology centre in London, UK.192 patients were mainly recruited from specialist clinics. We studied patients with Anderson-Fabry disease (AFD, n=17), dilated cardiomyopathy (DCM, n=31), hypertrophic cardiomyopathy (HCM, n=31), severe aortic stenosis (AS, n=66), cardiac AL amyloidosis (n=27) and myocardial infarction (MI, n=20). The results were compared with those for 81 normal subjects.In normal subjects, ECV (mean (95% CI), measured in the septum) was slightly higher in women than men (0.273 (0.264 to 0.282 vs 0.233 (0.225 to 0.244), p0.001), with no change with age. In disease, the ECV of AFD was the same as in normal subjects but higher in all other diseases (p0.001). Mean ECV was the same in DCM, HCM and AS (0.280, 0.291, 0.276 respectively), but higher in cardiac AL amyloidosis and higher again in MI (0.466 and 0.585 respectively, each p0.001). Where ECV was elevated, correlations were found with indexed left ventricular mass, end systolic volume, ejection fraction and left atrial area in apparent disease-specific patterns.Myocardial ECV, assessed non-invasively in the septum with equilibrium contrast cardiovascular magnetic resonance, shows gender differences in normal individuals and disease-specific variability. Therefore, ECV shows early potential to be a useful biomarker in health and disease.

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Background AFD is an X linked disorder of lysosomal storage that can have various cardiac manifestations, most commonly resulting in LVH. Echocardiographic data on LVH distribution emphasised concentric hypertrophy in males and later onset in females with less hypertrophy. However this modality is often limited in visualisation of the left ventricular apex. Methods 27 patients (mean age 47, 33% males, a large cohort of female heterozygotes) with genetically proven AFD were assessed by CMR for hypertrophy, its distribution and LGE.

Introduction Interstitial myocardial volume expansion is an important factor in cardiac disease but until recently could only be accurately assessed with myocardial biopsy. It is usually a result of diffuse fibrosis, but can also be caused by infiltration (such as by amyloid deposition) or oedema. We have used a new method, Equilibrium Contrast Cardiovascular Magnetic Resonance (EQ-CMR) to accurately quantify the interstitial space in normal subjects and across a broad spectrum of cardiac diseases. Methods The three steps in EQ-CMR are: (1) a primed gadolinium infusion to achieve contrast equilibrium, (2) Signal (T1) measurement pre and post equilibrium, (3) measurement of blood contrast volume (1−haematocrit). This allows calculation of the contrast volume of distribution, Vd(m), by: Vd ( m ) = ( 1 − haematocrit ) × Δ ( 1 / T1 ) myo ÷ Δ ( 1 / T1 ) blood . Vd(m) was measured in 278 subjects: 86 normal subjects (median age 43, range 24–81, 51% male) and 192 patients with Anderson-Fabry disease (AFD, n=17), dilated cardiomyopathy (DCM, n=31), hypertrophic cardiomyopathy (HCM, n=31), severe aortic stenosis (AS, n=66), cardiac AL amyloidosis (n=27) or myocardial infarction (MI, n=20). Results In normal subjects, mean Vd(m) was higher in females (0.274) than males (0.237, p Conclusions This study shows the ability of EQ-CMR to non-invasively quantify interstitial expansion using this novel technique in both the healthy population and a spectrum of differing cardiac diseases. Further work will build on this study to evaluate the potential role of Vd(m) as a clinical biomarker.

Senile systemic amyloidosis (SSA) is a rare cause of heart failure due to the deposition of wildtype transthyretin. The clinical features and outcome are ill defined; our aim was to evaluate the natural history of the disease in the UK in a group of thoroughly characterised patients. The series included all cases of biopsy proven transthyretin (TTR) amyloidosis with wildtype TTR gene sequencing who were prospectively followed up between January 2001 and May 2010. Clinical, biochemical, ECG and echocardiographic evaluation were performed at presentation to our centre. Patient survival was estimated using Kaplan–Meier analysis. 55 patients with histologically proven SSA; 36 (65.5%) from cardiac, 14 (25.4%) from GI tract, 3 (5.5%) from bladder, 1 (1.8%) from fat and 1 (1.8%) from carpal tunnel tissue were identified. 49 (89%) were male. The median age at diagnosis and death were 74 (range 66–89) and 79 (range 69–84) years respectively. Survival from symptom onset and diagnosis was 7.04 (range 0.54–8.41) and 4.58 (range 0.07–5.41) years respectively. In recent years more patients have been diagnosed with 2 (3.6%), 14 (25.5%) and 39 (70.9%) patients between 2001–2003, 2004–2006 and 2007–2009 respectively. The most common presentation was with breathlessness in 28 patients (51%). Twenty-four patients (43.6%) had prior carpal tunnel operations. Twelve (21.8%) patients had a history of ischaemic heart disease. Fifteen had had a coronary angiogram; 8 were reportedly normal and 7 required intervention. Arrhythmias were common, 20 patients (36.3%) had a history of atrial fibrillation and 6 (10.9) had pacemakers in situ. ECG findings were; 24 (43.6%) in AF, 6 (10.9%) first degree block, 10 (18.2%) left bundle and 6 (10.9%) right bundle branch block, 27 (49%) T wave changes, 11 (20%) 0.03 (45%). Ten patients (18%) had a detectable paraprotein and 2 (3.6%) had bence jones proteins. SSA is present in >25% of the very elderly at post mortem but was rarely diagnosed during life. It is becoming more frequently recognised perhaps due to widespread use of cardiac MRI. Most patients are male but women can be affected. A history of carpal tunnel syndrome is common. The diagnosis is often made after the onset of breathlessness. Systolic and diastolic dysfunction can be seen on echocardiogram. A positive troponin is a common finding with a subsequent normal coronary angiogram. Incidental paraproteins are prevalent in up to 8% of this population and it is important to obtain a tissue diagnosis to rule out AL amyloidosis. With supportive management medium term outcomes are good.

Background Cardiac involvement drives outcome in systemic AL amyloidosis. Late gadolinium enhancement (LGE) CMR is useful for the detection of cardiac amyloid, but characteristic LGE patterns do not always occur or may appear late in the disease. Using CMR T1 mapping, we measured the pre contrast myocardial T1 and myocardial Extracellular Volume (ECV), reflecting myocardial amyloidosis burden and determined their prognostic significance. Methods 102 patients underwent CMR and T1 mapping preand post contrast. Myocardial ECV was calculated at contrast equilibrium. 54 healthy volunteers served as controls. Patients were followed up for a median duration of 23 months and survival analyses were performed. A secondary analysis compared predictive power of the following techniques: pre contrast T1, post contrast T1, ECV at equilibrium (ECVi) and ECV at 15 minutes i.e. bolus only ECV (ECVb).

Background AA amyloidosis is the most serious potential complication of chronic inflammation and can result in renal failure and death. It is seen much less often in the USA than in Europe and is thought to have become less common in the developed world in general but there are few systematic data on its incidence and epidemiology. Objectives To analyze a single national centre experience of AA amyloidosis in the United Kingdom over the past 20 years. Methods Analysis of the UK National Amyloidosis Centres database and case records. Results 493 patients with confirmed AA amyloidosis were assessed at the UK National Amyloidosis Centre between 1992 and 2011. The referral rate has been stable at ∼30 new cases/yr over the past 12 yrs, in contrast with a three-fold increase among other types of amyloidosis. Median age at referral was 55 years, 54% were male and 81% of cases were ethnically white. The commonest underlying diseases are: rheumatoid arthritis (RA) 28%, chronic sepsis 19% and seronegative arthritis 10%, but in 18% the underlying inflammatory disease was uncharacterized at diagnosis. Comparing the cohort referred 1992-96 with the most recent 5 years, there has been a reduction in patients with RA from 33% to 19% (p 0.038), and juvenile idiopathic arthritis from 18% to 2% (p 20 ml/min is unchanged at 157 months. Median survival is 118 months with no significant difference between cohorts, but age at death has increased from a median of 60.6 yrs in the earliest cohort to 79 in the most recent (p Conclusions In contrast to a threefold increase in referrals of other types of amyloidosis during the past decade, referral rates for AA have not changed. Age at both diagnosis and death have increased significantly over the last 20 years. The incidence of AA amyloidosis among patients with inflammatory arthritis has decreased, perhaps reflecting greater use of biologic agents and a greater proportion of recent AA patients have uncharacterized underlying inflammatory disorders, posing challenges for clinical management. Disclosure of Interest None Declared

Background T1 mapping is a powerful technique for ECV quantification; native T1 has been shown to increase in a variety of conditions including oedema, fibrosis and amyloid. Iron and fat lower T1. Anderson Fabry disease (AFD) is a fat storage disease, cardiac iron occurs in transfusion dependent patients. We hypothesised that T1 lowering would diagnose early cardiac involvement, track disease severity and discriminate from other mimic pathologies. Methods

Abstract 2978 Background: Novel agents have emerged as important therapeutic options for plasma cell dyscrasias and consequently have been adopted into treatment strategies for Systemic AL amyloidosis. Several studies to date have shown the efficacy of immunomodulatory drugs (IMiD) in this disease. However, little data exists exploring the efficacy of these agents especially in the context of previous treatment lines. The primary objective of this study was to evaluate the response, OS and PFS in patients treated with lenalidomide regimens in the relapsed setting. Further analysis was carried out examining outcomes based on previous lines of therapy. The importance of continuous therapy for control of the clonal disease stable disease was also examined. Patients and Methods: Our primary cohort consisted of 66 AL amyloidosis patients who presented to our Centre between July 2007 and July 2012, identified from the database of the UK National Amyloidosis Centre, commencing a lenalidomide regimen in the relapsed setting. It was recommended that treatment continue until disease progression or unacceptable toxicity. Organ involvement and haematological and organ response were defined according to the 2010 consensus criteria. Overall survival (OS) was calculated from the start of lenalidomide treatment until death or last follow-up. Progression-free survival (PFS) was calculated from the start of lenalidomide treatment until relapse, death or last follow-up. Survival endpoints were examined based on previous lines of treatment. A subgroup analysis was carried out in those attaining at least stable disease to examine the impact of continuous therapy. In this cohort PFS was examined based on those remaining on continuous therapy versus those discontinuing treatment due to intolerance or patient preference. Results: The median age was 59.1 years (range 39.9–76.9) and 52% were male. A lambda clonal plasma cell dyscrasia was present in 62%. 44% had ≥ 3 organ involvement with 50% having cardiac involvement by echo criteria. Mayo cardiac staging (at diagnosis) was stage I, II and III in 30%, 62% and 8% respectively. The median number of previous treatment lines was 2 (range 1–5), with thalidomide and bortezomib pre-treatment in 80% and 68% respectively. Grade 3 toxicity was seen in 27% of patients and was mainly haematologic. A thrombotic complication was noted in 1 patient. On an intention-to-treat basis, 56% achieved a haematological response with a complete response in 11%. A dFLC response was observed in 57% and 26% achieved a dFLC-VGPR or better. The median follow-up of 12.4 months. The median OS was 46.3 months and the estimated 2-year PFS was 67% (figure 1). Compared to those who did not receive the drug, previous exposure to thalidomide did not confer a worse survival outcome (estimated 2-year OS 67% vs 67%, p = 0.59). Similarly, previous exposure to Bortezomib did not confer a worse survival (estimated 2-year OS OS 88% vs 79%, p=0.09). 58 patients (88%) achieved stable disease or better. In this subgroup, the median duration on lenalidomide was 17.2 months. The 2-year OS and PFS were 84% and 78% respectively. Compared to those who halted therapy, continuous treatment with lenalidomide correlated with an improved PFS (estimated 2-year PFS 62% vs 80% respectively, p = 0.02). Conclusion: This data further supports the effectiveness of lenalidomide containing regimens in the treatment of relapsed AL amyloidosis. Previous lines of therapy did not negatively impact survival outcomes. Continuous therapy is important in maximizing the duration of the clonal response. Disclosures: No relevant conflicts of interest to declare.

Abstract 2966 Introduction: Poor survival in AL amyloidosis is largely driven by outcomes in patients with advanced cardiac disease. To date, the Mayo cardiac staging system is the most widely used tool to identify these high risk patients. For stage III patients few treatment options exist to modify the natural history of this disease with up to 50% dying within the first 6 months. Moreover, there are currently no studies comparing different regimens in the novel agent era specifically addressing this group. Here we present a matched comparison examining response and survival endpoints after upfront treatment in Mayo stage III patients using either Cyclophosphamide, Bortezomib and Dexamethasone (CVD) or Cyclophosphamide, Thalidomide and Dexamethasone (CTD), the current standard of care for this disease in the United Kingdom. Patients and Methods: The primary cohort comprises 78 patients (39 in each arm) referred to the National Amyloidosis Centre in London between 2008–2012. All patients had cardiac involvement by the 2005 consensus criteria and all were Mayo stage III. The CVD cohort reflects all patients seen at the NAC with Mayo stage III disease treated with this regimen upfront. Based on baseline NT-proBNP (>8000ng/L) and dFLC (>180mg/L) the patients were then matched with a recent cohort treated with CTD as first line therapy. The CVD and CTD regimens were recommended as previously described (1, 2). Dose modifications were at the discretion of the treating haematologist. Both conventional haematologic responses and dFLC responses were examined (3, 4). Overall survival (OS) was calculated by the Kaplan-Meier method and calculated from the start of treatment until death or last follow-up. To correct for the influence of early deaths on response rates a landmark analysis was performed in patients surviving at least 3 months from treatment (n=21 (CVD) and n=30 (CTD)). Results: In the intention-to-treat (ITT) cohort response rates are comparable although there was a trend to higher CR rates with the CVD regimen (table 1). On an ITT basis, there was no statistically significant difference in the 1-year OS (59.4% vs 46.2% for CVD and CTD respectively, p = 0.9, figure 1a). A high rate of early deaths is noted. 23.7% of CVD and 13.1% of CTD patients died within 6 weeks (p = 0.24). 36.8% of CVD and 23.7% of CTD patients died within 3 months (p = 0.22). In the landmark analysis upfront therapy with CVD correlated with an improved 1-year OS (94% vs 62.1%, p = 0.01, figure 1 b). This may be partly driven by the increased CR rate in the CVD cohort compared to those receiving CTD (47% vs 24% respectively, p = 0.03, table 1). Conclusion: Compared with CTD, treatment with CVD was not associated with a reduction in the high rate of early deaths often seen in patients with Mayo cardiac stage III disease. However, these data suggest that survival of patients treated with CVD upfront may be superior among those who remain alive after the first 3 months, consistent with the higher CR rates achieved. While it did not reach statistical significance the high rate of early deaths indicates that further optimisation and better supportive care strategies are required during the early stages of treatment especially with CVD. Ongoing phase III trials are currently underway to address these issues in a prospective manner. The ITT cohort is shown in (A) and the landmark cohort is shown in (B). Solid and dashed lines reflect CVD and CTD treated patients respectively. Disclosures: Wechalekar: Janssen-Cilag: Honoraria.

Introduction Cardiac involvement drives prognosis in Systemic AL Amyloidosis, predicting outcome and influencing therapeutic options. Current methods of cardiac assessment do not quantify the myocardial amyloid burden. We used Equilibrium Contrast Cardiovascular Magnetic Resonance (EQ-CMR) to measure the cardiac interstitial compartment, measured as the myocardial contrast volume of distribution, Vd m , which we hypothesised would reflect the amyloid burden. Methods Patients with systemic AL amyloidosis undergoing routine work up at the National Amyloidosis Centre were recruited (n=60, 39 males, 21 females, mean age 63 years) and underwent conventional CMR including late enhancement, EQ-CMR to measure Vd m and standard cardiac work-up including ECG, echocardiography, biomarkers (BNP, Troponin T) and functional assessment (6-min walk test, 6MWT, where permitted by autonomic neuropathy). Results were compared to normal controls. Conventional assessment ranked cardiac involvement as definite, probable and none. Results Vd m was significantly higher in patients than normal controls (0.25 vs 0.40, p m of 0.276 vs 0.342 vs 0.488, p m correlated with cardiac parameters by echo (eg, TDI S-wave R 2 0.27, p 2 0.31, p 2 0.47, p 2 0.28, p=0.006). Vd m was associated with ECG abnormalities and tracked small QRS voltages (R 2 0.33, p m correlated with a lower 6MWT outcome (R 2 0.13, p=0.03). Conclusions The measurement of the myocardial interstitial compartment (Vd m ) using EQ-CMR in systemic AL amyloidosis quantifies the cardiac amyloid burden.

Background Cardiac MRI (CMR) is increasingly used to further investigate patients in whom amyloidosis is suspected on echocardiography. Late gadolinium enhancement (LGE) reflects expansion of the interstitium, and circumferential subendocardial LGE has been reported to be a typical finding in AL amyloidosis; by contrast, a more diffuse transmural LGE pattern has been associated with ATTR (transthyretin amyloidosis).

Summary In this study we have used Equilibrium contrast CMR (EQ-CMR) to evaluate the cardiac insterstium in healthy volunteers creating a table of normal values and finding no correlation with age, but differences with gender, height and hematocrit. Background EQ-CMR is a new method for assessment of the myocardial contrast volume of distribution, Vd(m), a marker of interstitial space. We used EQ-CMR to assess the Vd (m) in healthy volunteers to ascertain normal age/gender values. Methods 86 healthy subjects (median age 45, range 24-81, 42 males) were recruited from hospital, university or via a local General Practitioner surgery. All were assessed with a cardiac history and examination, routine blood tests, 12 lead ECG, blood pressure and clinical CMR. Volunteers were excluded if any evidence of cardiovascular disease was found. Baseline differences between male and female volunteers were found, with the latter having a faster heart rate, smaller left ventricular volumes, shorter height, lower weight and lower hematocrit. Results Mean Vd(m) was 0.255±0.035. There was no significant correlation between age and Vd(m) (R=0.15, P=0.16, Fig 1). Vd(m) in females was significantly higher than males (0.275±0.028 vs 0.237±0.031, P

Abstract 992 Background: There have been few prospective clinical trials in AL amyloidosis; existing prospective studies in this heterogeneous disease have been hampered by small patient numbers due to rarity of the condition, a lack of validated endpoints and high cost. More importantly, they have been subject to considerable bias due to almost complete exclusion of poor prognosis patients. Aims: The aims of this prospective observational study, was to include all patients with systemic AL amyloidosis regardless of age or disease severity, in order to convey a ‘real-world' picture of the disease, its response to myeloma-type chemotherapy regimens, associated toxicity and outcomes in terms of amyloidotic organ function, quality of life (QoL) and survival. Methods: All patients referred to the UK National Amyloidosis Centre (NAC) from 1st September 2009 were screened for participation in the AL chemotherapy study (ALchemy). Patients were eligible if they were newly diagnosed with systemic AL amyloidosis and in need of chemotherapy. At each NAC evaluation (baseline, after completion of 3 cycles of chemotherapy and 6, 12, 18 and 24 months) the underlying clonal disease was assessed by sFLC assay and serum and urine electrophoresis; amyloidotic organ dysfunction/response was assessed according to the international consensus criteria. At baseline patients underwent bone marrow examination, assessment of whole-body amyloid load by 123I-SAP scintigraphy, and completed a QoL questionnaire. Amyloid burden was monitored 6 monthly thereafter, and QoL after 3 cycles and yearly thereafter. Clonal disease assessments were undertaken monthly throughout the duration of the study and toxicity assessments during periods of chemotherapy. Patients received chemotherapy in local hematology centers and regimens and doses were at the discretion of treating physicians. Results: Two hundred and fifty patients were recruited in 2 years; 57% were male. Median age at presentation was 64 years (IQR 57 to 73). At baseline evaluation, which occurred a median of 1 month from diagnosis, 20% of patients had Mayo stage 1 disease, and 40% each had stage 2 and 3 disease. Renal (50%) and cardiac (31%) presentations predominated. At censor, 9 (4%) patients had died prior to starting chemotherapy and 217 (87%) patients had received at least one cycle and were thus considered ‘evaluable'. First-line treatment was with CTD in 168 (77%) cases, 89% of whom received dose attenuation. Nineteen (9%) patients received a melphalan- or bortezomib-based regimen first line. One third of those patients who commenced chemotherapy underwent a regimen change, usually (82%) to one containing bortezomib, either as monotherapy (9 patients) or in combination with dexamethasone and/or cyclophosphamide (47 patients). On an intention to treat basis, 20% patients died before reaching the 3 cycle timepoint and a further 9% were withdrawn or lost to follow up. Among the 154 remaining evaluable patients, the 3 cycle evaluation resulted in continuation of the same chemotherapy regimen in 42% cases, a switch of regimen in 21% cases, and cessation of chemotherapy altogether in 28% cases. At this timepoint, clonal CR, VGPR, PR and NR rates among evaluable patients were 35%, 9%, 30% and 26% respectively. Toxicity ≥grade 3 occurred in 49% of patients with a total of 359 episodes. The commonest severe toxicities were fluid overload (61%), lethargy (38%), infection (26%), hypotension (18%) and neuropathy (12%). Of 217 patients, 111 (51%) were admitted with a total of 148 hospitalizations, most commonly due to fluid overload or infection. After median follow-up of 7 months, 29% of patients had died. Mayo stage 3 disease, dominant cardiac presentation and inadequate clonal response after 3 cycles were independent risk factors for death. Achieving a dFLC response >65% after the first cycle of chemotherapy, appeared to overcome the poor prognosis associated with Mayo Stage 3 disease. Conclusion: ALchemy is fast becoming the largest prospective study in AL amyloidosis and has provided a wealth of information on treatment, toxicity and outcome in a real-world clinical setting. The inclusion of most patients, regardless of disease severity, indicates a persistently poor prognosis among a substantial proportion of patients who are ineligible for randomized controlled trials, and highlights the unmet need for improved diagnosis and treatment. Disclosures: No relevant conflicts of interest to declare.

Objectives: This study sought to explore the potential role of noncontrast myocardial T1 mapping for detection of cardiac involvement in patients with primary amyloid light-chain (AL) amyloidosis. Background: Cardiac involvement carries a poor prognosis in systemic AL amyloidosis. Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) is useful for the detection of cardiac amyloid, but characteristic LGE patterns do not always occur or they appear late in the disease. Noncontrast characterization of amyloidotic myocardium with T1 mapping may improve disease detection. Furthermore, quantitative assessment of myocardial amyloid load would be of great value. Methods: Fifty-three AL amyloidosis patients (14 with no cardiac involvement, 11 with possible involvement, and 28 with definite cardiac involvement based on standard biomarker and echocardiographic criteria) underwent CMR (1.5-T) including noncontrast T1 mapping (shortened modified look-locker inversion recovery [ShMOLLI] sequence) and LGE imaging. These were compared with 36 healthy volunteers and 17 patients with aortic stenosis and a comparable degree of left ventricular hypertrophy as the cardiac amyloid patients. Results: Myocardial T1 was significantly elevated in cardiac AL amyloidosis patients (1,140 ± 61 ms) compared to normal subjects (958 ± 20 ms, p < 0.001) and patients with aortic stenosis (979 ± 51 ms, p < 0.001). Myocardial T1 was increased in AL amyloid even when cardiac involvement was uncertain (1,048 ± 48 ms) or thought absent (1,009 ± 31 ms). A noncontrast myocardial T1 cutoff of 1,020 ms yielded 92% accuracy for identifying amyloid patients with possible or definite cardiac involvement. In the AL amyloidosis cohort, there were significant correlations between myocardial T1 time and indices of systolic and diastolic dysfunction. Conclusions: Noncontrast T1 mapping has high diagnostic accuracy for detecting cardiac AL amyloidosis, correlates well with markers of systolic and diastolic dysfunction, and is potentially more sensitive for detecting early disease than LGE imaging. Elevated myocardial T1 may represent a direct marker of cardiac amyloid load. Further studies are needed to assess the prognostic significance of T1 elevation. © 2013 American College of Cardiology Foundation.

Background Cardiac involvement drives prognosis in amyloidosis. ECV directly quantitates interstitial expansion and hence myocardial amyloid burden. Native T1 is also elevated in amyloid but reflects both cell and interstitial changes. The combination gives insight into amyloid burden and the myocyte response. Previously we have shown the utility of both techniques in AL amyloidosis. Here, we explore the differences between the two main types of amyloid, AL and ATTR types.

Background Transthyretin amyloidosis (ATTR amyloidosis) is an under diagnosed cause of heart failure with no truly quantitative test. Cardiac involvement is the leading cause of death and influences therapeutic choices. Since new therapies are imminent which aim to treat ATTR amyloidosis the lack of a quantitative test represents a critical step for drug development. In cardiac AL amyloidosis, T1 has high diagnostic accuracy and tracks disease. We hypothesised similar results would occur for ATTR. We hypothesized that the native myocardial T1 would be elevated in ATTR amyloid; that T1 elevation would track the cardiac amyloid burden as measured by DPD grading; and that T1 elevation would be an early disease marker. Methods

Background Late gadolinium enhancement (LGE) identifies focal myocardial fibrosis. However it misses diffuse fibrosis and makes all “above threshold” areas of ECV expansion appear as LGE. We hypothesized that LGE area in different cardiac diseases would have varying degrees of interstitial expansion and consequently have different ECV values. Methods 75 patients were prospectively enrolled: “Chronic MI": 6 months after myocardial infarction (n=25); “HCM” hypertrophic cardiomyopathy (n=25), and healthy volunteers (n=25). Patients with HCM and no LGE were excluded. As the conditions for dynamic contrast equilibrium are not reached in infarction, equilibrium contrast was performed. The T1 mapping sequence was ShMOLLI. The contrast agent was Gadoterate meglumine (Dotarem) at 0.1mmol/Kg (bolus) plus infusion at 15minutes at 0.0011 mmol/kg/min. CMR was at 1.5T (Siemens Avanto). Regions of interest were drawn in the LV blood pool, the region of LGE and in the remote myocardium (which was a non-hypertrophied area in the HCM patients) to generate ECV values calibrated to hematocrit. Results