Author + information
- Received December 6, 2017
- Revision received February 7, 2018
- Accepted February 8, 2018
- Published online November 14, 2018.
- Ana Martinez-Naharro, MDa,
- Tushar Kotecha, MBChBa,b,
- Karl Norrington, MBBSa,
- Michele Boldrini, MDa,
- Tamer Rezk, MBBSa,
- Candida Quarta, MD, PhDa,
- Thomas A. Treibel, PhDb,c,
- Carol J. Whelan, MDa,
- Daniel S. Knight, MDa,
- Peter Kellman, PhDd,
- Frederick L. Ruberg, MDe,
- Julian D. Gillmore, MD, PhDa,
- James C. Moon, MDb,c,
- Philip N. Hawkins, PhDa and
- Marianna Fontana, MD, PhDa,∗ ()
- aNational Amyloidosis Centre, Division of Medicine, University College London, Royal Free Hospital, London, United Kingdom
- bInstitute of Cardiovascular Science, University College London, London, United Kingdom
- cBarts Heart Centre, West Smithfield, London, United Kingdom
- dNational Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland
- eAmyloidosis Center and Section of Cardiovascular Medicine, Department of Medicine, Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. Marianna Fontana, National Amyloidosis Centre, University College London, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, United Kingdom.
Objectives This study evaluated the prognostic potential of native myocardial T1 in cardiac transthyretin amyloidosis (ATTR) and compared native T1 with extracellular volume (ECV) in terms of diagnostic accuracy and prognosis.
Background ATTR is an increasingly recognized cause of heart failure that has an overlapping clinical phenotype with hypertrophic cardiomyopathy (HCM). Native T1 mapping by cardiac magnetic resonance (CMR) is useful for diagnosis in cardiac amyloidosis but its prognostic potential has never been assessed.
Methods A total of 134 patients with wild-type ATTR (ATTRwt) (122 men; age 76 ± 7 years), 81 patients with hereditary-type ATTR (ATTRm) (60 men; age 69 ± 11 years), 44 patients with HCM (32 men; age 51 ± 13 years), and 12 asymptomatic mutation carriers (4 men; age 47 ± 10 years) were studied. All subjects underwent CMR with T1 mapping and ECV measurement. ATTR patients also underwent 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy.
Results Native T1 and ECV were elevated in ATTR compared with HCM (p < 0.001) and were both associated with a high diagnostic accuracy (area under the curve [AUC]: 0.87; 95% confidence interval [CI]: 0.82 to 0.91) for T1 and an AUC of 0.91 (95% CI: 0.87 to 0.94) for ECV. No significant difference in native T1 and ECV was found between ATTRwt and ATTRm, and ECV correlated well with 99mTc-DPD scintigraphy. During follow-up of a mean of 32 ± 17 months, 55 ATTRwt and 40 ATTRm patients died. Native T1 and ECV predicted death (T1: hazard ratio [HR]: 1.225 for each 59-ms increase; 95% CI: 1.010 to 1.486; p < 0.05; ECV: HR: 1.155 for each 3% increase; 95% CI: 1.097 to 1.216; p < 0.001), but only ECV remained independently predictive after adjustment for age, N-terminal pro−B-type natriuretic peptide, left ventricular ejection fraction, E/E′, left ventricular mass index, DPD grade, and late gadolinium enhancement.
Conclusions Native T1 mapping and ECV are good diagnostic techniques for cardiac ATTR that are associated with prognosis. Both parameters correlated with mortality, but only ECV remained independently predictive of prognosis, suggesting that it is a more robust marker in cardiac ATTR.
Systemic amyloidosis is caused by deposition of insoluble amyloid fibrils in the extracellular space of tissues and organs, which leads to progressive organ failure and death. More than 30 different precursor proteins have the propensity to form amyloid fibrils (1), but only 2 types account for most cases of cardiac amyloidosis: immunoglobulin light-chain and transthyretin amyloidosis (ATTR). ATTR, in turn, may be either hereditary (ATTRm), arising from misfolding of mutated TTR, or nonhereditary, caused by misfolding of wild-type transthyretin (ATTRwt; also known as senile systemic amyloidosis). Cardiac involvement is the principal driver of prognosis in systemic amyloidosis although outcome differs markedly between types (2).
Cardiac ATTR is a progressive and usually fatal cause of heart failure; it typically occurs in older people, for which awareness and clinical recognition have greatly increased in recent times.
Formerly, diagnosis of cardiac ATTR required demonstration of amyloid deposits with an endomyocardial biopsy (3), but advances in diagnostic imaging, including cardiac magnetic resonance (CMR) (4,5) and repurposed bone scintigraphy (6–9), together with blood and/or urine exclusion of free light chains, have now enabled noninvasive, nonhistological diagnosis of cardiac ATTR, which has resulted in a >30-fold increase in the diagnosis of this condition in our center during the past decade (10).
CMR has lately emerged as a robust technique that can provide unique information about tissue composition. CMR can visualize, with late gadolinium enhancement (LGE), and measure, with T1 mapping, the continuum of cardiac amyloid deposition. T1 mapping, before the administration of contrast (4,11), can measure the intrinsic signal from the myocardium (native myocardial T1), and pre- and post-administration of gadolinium-based contrast, T1 can be used to calculate the myocardial extracellular volume (ECV). Both native myocardial T1 and ECV have been extensively validated in cardiac amyloidosis as surrogate markers of infiltration. They have been shown to correlate with disease burden, to detect early disease, and have good diagnostic accuracy (4,11). Furthermore, in cardiac light-chain amyloidosis, higher T1 and ECV measurements have been shown to be associated with a shorter event-free survival (12). However, although the prognostic significance of ECV has been shown (13) for ATTR, neither the prognostic potential of native T1, nor the relative diagnostic accuracy or ability for native T1 versus ECV to track disease severity have been studied.
From anecdotal observation and our previous work in light-chain amyloidosis, we hypothesized that native myocardial T1 predicts survival in cardiac ATTR (12), and that there may be significant differences between the ability of native T1 and ECV to track disease progression.
Ethical approval was granted by the University College London/University College London Hospitals Joint Committees on the Ethics of Human Research Committee, and all participants provided written informed consent.
A total of 271 subjects were prospectively recruited between 2011 and 2015. The study population underwent comprehensive clinical evaluation at the National Amyloidosis Centre, London, and consisted of the 3 groups described in the following. Patients were systematically followed up until June 13, 2017, the date of censoring.
Cardiac ATTR was defined as the combination of symptoms with an echocardiogram consistent with or suggestive of cardiac amyloidosis, grade 2 or 3 cardiac uptake on 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy in the absence of a monoclonal gammopathy, or in the presence of monoclonal gammopathy, a cardiac biopsy that confirmed ATTR (14). Possible cardiac ATTR was defined by grade 1 cardiac uptake on 99mTc-DPD scintigraphy in the absence of a monoclonal gammopathy (4,13). All subjects underwent sequencing of exons 2, 3, and 4 of the TTR gene.
Of the 271 subjects included in this study, 198 had definitive cardiac ATTR (171 men, 86%; age 74 ± 8 years), 17 had possible cardiac ATTR (11 men, 65%; age 70 ± 14 years), 12 were TTR gene mutation carriers, and 44 had hypertrophic cardiomyopathy (HCM).
TTR gene mutation carriers
Individuals with amyloidogenic TTR gene mutations were defined as carriers on the basis of being clinically asymptomatic, having no cardiac uptake on 99mTc-DPD scintigraphy and normal echocardiography, CMR, N-terminal pro−B-type natriuretic peptide (NT-proBNP), and troponin T. Twelve TTR gene mutation carriers were recruited (4 men, 33%; age 47 ± 11 years).
There were 44 patients with HCM (32 men, 73%; 51 ± 13 years) who fulfilled the diagnostic criteria. HCM was defined by the presence of increased ventricular wall thickness or mass in the absence of loading conditions (hypertension, valve disease) sufficient to cause the observed abnormality (15). In addition to the previously described TTR gene carrier group, HCM patients constituted the noncardiac ATTR group.
We excluded patients with contraindications to CMR, including those with a glomerular filtration rate of <30 ml/min.
All participants underwent standard CMR on a 1.5-T clinical scanner. A standard volumetric and LGE study was performed. The gadolinium-based contrast agent used was 0.1 mmol/kg of gadoterate meglumine (Dotarem, Guerbet S.A., France). LGE imaging was acquired using magnitude reconstruction in all patients and phase-sensitive inversion recovery reconstruction in 82% of patients with either a standard fast, low-angle shot inversion recovery or balanced steady-state free precession sequence. For native and post-contrast T1 mapping, 4-chamber long-axis images were acquired using the shortened modified look-locker inversion recovery sequence after regional shimming (16). After a bolus of contrast and standard LGE imaging, the T1 measurement was repeated with the shortened modified look-locker inversion recovery sequence (17).
CMR image analysis
All CMR images and maps were analyzed offline. T1 measurement was performed by drawing a region of interest in the basal to mid septum of the appropriate 4-chamber map. For ECV measurement, a single region of interest was drawn in each of the 4 required areas: myocardial T1 estimates (basal to mid septum in the 4-chamber map) and blood T1 estimates (left ventricular [LV] cavity blood pool in the 4-chamber map, avoiding the papillary muscles) before and after contrast administration. Hematocrit was measured in all subjects immediately before each CMR study. ECV was calculated as: myocardial ECV = (1-hematocrit) × (ΔR1myocardium/ΔR1blood), where R1 = 1/T1.
Before our adoption of phase-sensitive inversion recovery reconstruction for all amyloidosis patients, because myocardial nulling can be difficult in the presence of amyloid, any confusion with magnitude reconstruction images was resolved by selecting the images that most matched the post-contrast T1 maps, with bright LGE expected to correlate with areas of the lowest post-contrast T1 (i.e., the highest gadolinium concentration, the highest interstitial expansion).
The LGE pattern was classified into 3 groups according to the degree of transmurality: group 1, no LGE; group 2, subendocardial LGE (when there was global subendocardial but no transmural LGE); and group 3, transmural LGE (when the LGE extended transmurally). A scan was classified by the most extensive LGE identified. Thus, a patient with basal transmural LGE but apical subendocardial LGE would be classified as transmural (5).
Subjects were scanned using hybrid single-photon emission computed tomography (SPECT) computed tomography (CT) gamma cameras following administration of 700 MBq of intravenously-injected 99mTc-DPD. Whole-body planar images were acquired after 3 h, followed by SPECT of the heart, coupled with a low-dose, noncontrast CT scan (18). Gated and nongated cardiac SPECT reconstruction and SPECT-CT image fusion was performed on the Xeleris workstation (GE Healthcare, Wauwatosa, Wisconsin). Cardiac retention of 99mTc-DPD was scored visually according to the grading devised by Perugini et al. (6) using the following grading system: grade 0, absent cardiac uptake; grade 1, mild cardiac uptake less than bone; grade 2, moderate cardiac uptake equal or greater than bone; and grade 3, intense cardiac uptake associated with substantial reduction or loss of bone signal. Uptake was verified by visual review of SPECT imaging.
Statistical analysis was performed using IBM SPSS Statistics version 22 (IBM, Armonk, New York). All continuous variables were normally distributed (Shapiro-Wilk test), other than NT-proBNP, which was natural log transformed for bivariate testing. These are presented as mean ± SD, with untransformed NT-proBNP presented as median and interquartile range. Comparisons between multiple groups were performed by 1-way analysis of variance with post hoc Bonferroni correction. The chi-square test or Fischer’s exact test was used to compare categorical data as appropriate. Correlations between parameters were assessed using Pearson’s r or Spearman’s rho. Receiver-operating characteristic (ROC) curve analysis was performed to define the diagnostic accuracy of native T1 and ECV. The areas under the curves (AUC) were compared statistically for correlated ROC curves with the DeLong method.
Survival was evaluated using Cox proportional hazards regression analysis, providing estimated hazard ratios (HRs) with 95% confidence intervals (CIs) and Kaplan-Meier curves. All variables were first explored with univariate Cox regression. Separate multivariate models evaluated the independent predictive value of T1 and ECV above other clinically and statistically significant covariates. Statistical significance was defined as p < 0.05.
The characteristics of the 271 subjects are shown in Table 1. A total of 198 patients with definitive ATTR, 17 patients with possible ATTR, and 12 mutation carriers were enrolled. These subjects were compared with 44 patients with HCM.
Of the patients with definitive ATTR, 125 had ATTRwt and 73 had ATTRm. The TTR mutations were V122I (n = 40); T60A (n = 20); V30M (n = 5); and S77Y, E54G, E54L, E89K, D38Y, F44L, G89L, and L12P in 1 case each. Among 17 patients with suspected cardiac ATTR (DPD grade 1, 1 DPD scintigraphy), 9 had the wild-type TTR gene sequence and 8 had amyloidogenic TTR gene mutations that consisted of S77Y (n = 3) and V30M, I107F, E54G, G47V, and I84S in 1 case each. The variants present in mutation carriers were T60A (n = 6); V30M (n = 5), and S77Y (n = 1).
Correlation between T1 and ECV
Native T1 and ECV had good correlation (R = 0.726) in all ATTR subjects, and this correlation remained good in low ECV values (R = 0.735 in ECV <0.40). However, this correlation was significantly worse when high ECV values were analyzed (R = 0.351 in ECV ≥0.40) (Figures 1 and 2⇓⇓). Native T1 and ECV also had good correlation in HCM patients (R = 0.684).
T1 and ECV diagnostic accuracy
As predicted, T1 and ECV were elevated in ATTR patients compared with HCM and mutation carriers (native T1: 1,096 ± 51 ms vs. 1,013 ± 64 ms, p < 0.001; ECV: 0.61 ± 0.12 vs. 0.36 ± 0.13; p < 0.001).
The ROC curve analysis was performed for the discrimination of definitive cardiac ATTR or possible cardiac ATTR from the combined differential diagnoses of HCM or ATTR mutation carriers without evidence of cardiac amyloidosis.
The combined group of definitive ATTR and possible ATTR patients had AUC ROC curves of 0.87 (95% CI: 0.82 to 0.91) for T1 and 0.91 (95% CI: 0.87 to 0.94) for ECV. The T1 cutoff value to diagnose definitive or possible cardiac ATTR was 1,048 ms, with a specificity of 80.36% and sensitivity of 86.54%; for ECV, the cutoff value was 0.469, with a specificity of 82.14% and sensitivity of 92.46%.
When a subgroup analysis was performed according the ATTR etiology (ATTRm, ATTRwt) diagnostic accuracy remained similarly good. The AUC for T1 in ATTRm was 0.88 (95% CI: 0.82 to 0.93) compared with an AUC for ECV of 0.92 (95% CI: 0.87 to 0.96). T1 and ECV also had similar diagnostic accuracy in ATTRwt patients; the T1 AUC was 0.86 (95% CI: 0.80 to 0.90), and ECV had an AUC of 0.90 (95% CI: 0.85 to 0.94) (Figure 3). The T1 cutoff value to diagnose definitive or possible cardiac ATTRm was 1,051 ms, with a specificity of 82.14% and sensitivity of 86.08%; the cutoff value for ECV was 0.469, with a specificity of 82.14% and sensitivity of 91.89%. The T1 cutoff value to diagnose definitive or possible cardiac ATTRwt was 1,048 ms, with a specificity of 80.36% and sensitivity of 86.05%; the cutoff value for ECV was 0.469, with a specificity of 82.14% and sensitivity of 92.80%.
There were no statistically significant differences in the AUC for native T1 and ECV in all subgroup comparisons.
T1, ECV, and DPD/LGE findings, cardiac function, biomarkers and 6-minute walk test
Both native T1 and ECV increased with increasing cardiac uptake as assessed by bone scintigraphy (p < 0.001 for trend). Native T1 and ECV were not elevated in mutation carriers (native T1: 968 ± 41 ms; ECV: 0.29 ± 0.03) but were elevated in the 17 patients with possible ATTR (DPD grade 1) (native T1: 1,023 ± 64 ms; ECV: 0.41 ± 0.13; p < 0.05 for both), all of whom had no amyloid-like LGE by CMR, with the exception of patients with the Se77Tyr variant (Figure 4).
Native T1 and ECV values were also elevated in HCM patients compared with ATTR mutation carriers (native T1 1,026 ± 64 ms; ECV: 0.38 ± 0.15; p < 0.05 for both).
Correlations were broadly similar for T1 and ECV across ATTR types (Table 2), but ECV correlated more strongly with parameters of cardiac function, biomarkers, and the 6-min walk test than T1. Overall, in all ATTR patients, T1 and ECV correlated with indexes of systolic and diastolic function, indexed LV mass, and known prognostic biomarkers, as well as functional markers (6-min walk test performance), in keeping with our previous findings (4,11,12). Furthermore, ECV correlated with indexed stroke volume but T1 did not.
For subgroup analyses (ATTRm and ATTRwt), correlations were lower, reflecting the smaller sample sizes.
In asymptomatic ATTR mutations carriers, there were no statistically significant correlations.
Association between T1 and ECV and outcome
At follow-up (mean 32 ± 17 months), 95 of 227 (42%) subjects had died (55 with ATTRwt and 40 with ATTRm). Native T1 and ECV predicted death in the ATTR population (T1: HR: 1.225 for each 59-ms increase; 95% CI: 1.010 to 1.486; p < 0.05; ECV: HR: 1.155 for each 3% increase; 95% CI: 1.097 to 1.216; p < 0.001). ECV also predicted death separately in the ATTRwt and ATTRm groups (p < 0.01 for both). However, native T1 was not predictive of death when the ATTRwt and ATTRm groups were analyzed separately (Figure 5).
ECV remained significantly associated with mortality (HR: 1.101; 95% CI: 1.022 to 1.187; p < 0.05) in multivariate Cox models that included age, NT-proBNP, LV ejection fraction, E/E′, LV mass index, and DPD grade. Only age, ECV, and NT-proBNP remained significantly associated with mortality when LGE was added to the multivariate model (ECV: HR: 1.106 for each 3% increase; 95% CI: 1.011 to 1.209; p < 0.05; LGE: HR: 0.868; 95% CI: 0.447 to 1.973; p = 0.939). In contrast, native T1 did not remain significantly associated with mortality after adjustment for age, NT-proBNP, LV ejection fraction, E/E′, LV mass index, and DPD grade (p = 0.971). Native T1 remained not significant after the addition of LGE to the model (p = 0.729).
In this large ATTR population, for the first time, we described that native T1 mapping and ECV are good diagnostic techniques in cardiac ATTR; however, in high levels of infiltration, native T1 and ECV could be discordant. Both parameters also correlated with mortality in cardiac ATTR. Nevertheless, only ECV remained independently predictive of prognosis, which suggested that it is a more robust marker in cardiac ATTR (Online Tables 1 and 2). In addition, we demonstrated that nondiagnostic DPD uptake (grade 1), which was previously believed to be indeterminate but inconsistent with definitive ATTR, is associated with abnormal myocardial T1 and ECV, which suggested that CMR could detect a phenotype of early amyloid infiltration.
Native T1 and ECV have lately emerged as the first noninvasive quantitative markers of myocardial amyloid infiltration. Our earlier work in ATTR demonstrated that elevated native myocardial T1 in cardiac ATTR was more sensitive than LGE imaging and had high diagnostic accuracy. Similarly, ECV was also elevated in patients with early stage disease when conventional clinical testing and LGE were normal; it tracked a range of markers of disease severity and was correlated with prognosis in ATTR (13). Although initial studies suggested the 2 biomarkers had similar clinical implications, important differences recently emerged between the 2 main types of cardiac amyloidosis, with native T1 being relatively higher in light-chain amyloidosis compared with ATTR, and vice versa for ECV (19). The present study extended these intriguing observations. We demonstrated that native T1 was correlated with prognosis in ATTR and highlighted differences between the 2 biomarkers in ATTR, in which both native T1 and ECV showed a similar diagnostic accuracy, but ECV had a significantly better correlation with all markers of amyloid burden and better prognostic power than native T1. We also demonstrated a good correlation between ECV and native T1 for a low level of infiltration but poor correlation when amyloid burden was moderate or severe.
We believe that these differences represent different biological information provided by native T1 and ECV measurements. Cardiac amyloidosis is emerging as a spectrum characterized by variable degrees of amyloid infiltration, myocardial edema, inflammation, and differential myocyte response with myocyte hypertrophy. The administration of contrast and ECV measurements enabled us to isolate the signal from the extracellular space, but native myocardial T1 provided a composite signal from the intra- and extracellular spaces, a signal that was potentially influenced by other pathophysiological mechanisms beyond simple amyloid load. Native myocardial T1 is highly influenced by water content in the tissue, and therefore, will be significantly raised by the presence of myocardial edema (20). There are 2 types of myocardial edema: intracellular and extracellular. ECV is elevated when there is extracellular edema, and T1 is elevated in both types (21). Therefore, myocardial edema influences both native T1 and ECV; however, this influence is disproportionate when the edema is mainly intracellular, with the degree of elevation being higher in native T1 than in ECV. In contrast, a relative increase in myocyte hypertrophy compared with amyloid burden will likely decrease the native T1.
In cardiac ATTR, progressive amyloid deposition is believed to be the main driver of disease progression, whereas in light-chain amyloidosis, light-chain toxicity or rate of amyloid deposition are believed to also play an important role, especially in contributing to early mortality. In this context, the better correlation of ECV, not only with markers of disease severity but also with prognosis in ATTR, is not surprising, but maintains the hypothesis of ECV being a better marker of amyloid deposition. This hypothesis is also in line with the different significance of native T1 in light-chain amyloidosis as a powerful independent predictor of prognosis, because the ability to track both amyloid load and associated myocardial edema is important in this particular amyloid subtype.
Different roles emerged for measurements of native T1 and ECV in ATTR from this study. The similar diagnostic performance supported the use of native T1 for diagnosis of ATTR, which also had the significant advantage of being a noncontrast technique. Lack of requirement for contrast means that native myocardial T1 mapping can be performed in patients with advanced renal failure, in whom administration of contrast is contraindicated. However, in this study, we excluded patients with severe renal impairment, which left a knowledge gap about the clinical usefulness of noncontrast CMR in this setting. Lack of need to give contrast is also attractive in the general population because of reduced cost and recent potential concerns about gadolinium accumulating in the brain, although this has not been demonstrated for the cyclic gadolinium agents, such as those used in this study (22). In contrast, ECV is a better marker in ATTR for risk stratification and probably for tracking disease progression. These differences were also supported and were at least in part explained by the relationship between native T1 and ECV. There was a good correlation between native T1 and ECV up to an ECV of 0.4, but when the ECV expansion was higher, the correlation between the 2 measurements became poor. The inability of native T1 to track increasing amyloid burden when the ECV was >0.4 likely represented the main reason for the worse prognostic performance of native myocardial T1 compared with ECV. Both biomarkers did increase in subclinical disease, which supported their equivalent role as diagnostic markers, as confirmed by similar AUCs in the ROC curve analysis.
Cardiac biopsy was available in only a minority of patients, but this cohort of patients was fully characterized using the validated and now widely used noninvasive criteria for ATTR (14). Patients with pacemakers or defibrillators were also excluded. A wide range of TTR mutations were included in the analysis. In this study, T1 measurements were performed by drawing a region of interest in the basal to mid septum of the appropriate 4-chamber map. The same approach was used for ECV measurements; therefore, the total extent of cardiac amyloid infiltration was not assessed. T2 maps were not acquired in this study, which limited the possibility of exploring the hypothesis of myocardial edema as a potential mechanism for the increase in T1. Finally, this was a single-center study in which 1 T1 mapping technique was used. Care must be taken with interpretation of the different T1 cutoffs because T1 varies with magnetic field strength and different sequences, thus establishment of normal ranges for a given system with use of standardization tools is recommended.
CMR-determined native myocardial T1 and ECV provided excellent diagnostic accuracy for identification of cardiac ATTR, and both methodologies tracked cardiac uptake on DPD scintigraphy well. Native T1 and ECV predicted survival in ATTR; however, ECV was a more robust predictor. ECV, a noninvasive quantification of the cardiac amyloid burden, remained an independent predictor of prognosis after adjustment for known prognostic factors and provided unique insight into tissue composition in cardiac amyloidosis.
COMPETENCY IN MEDICAL KNOWLEDGE: Native myocardial T1 and ECV have similar diagnostic accuracy identifying ATTR and both correlate with mortality. However, ECV is a more robust prognostic predictor, remaining an independent predictor of prognosis after adjustment for known prognostic factors.
TRANSLATIONAL OUTLOOK: Future studies in cardiac amyloidosis by CMR with T2 mapping could help to identify differences in amyloid biology in the main 2 types of cardiac amyloidosis (light-chain and ATTR).
Dr. Norrington is deceased.
Dr. Moon has received an unrestricted research grant from GlaxoSmithKline and has also been paid a consultancy fee for trial design. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Drs. Martinez-Naharro and Kotecha contributed equally to this work and are joint first authors.
- Abbreviations and Acronyms
- transthyretin amyloidosis
- hereditary transthyretin amyloidosis
- wild-type transthyretin amyloidosis
- area under the curve
- confidence interval
- cardiac magnetic resonance
- computed tomography
- extracellular volume fraction
- hypertrophic cardiomyopathy
- hazard ratio
- late gadolinium enhancement
- left ventricular
- N-terminal pro-brain natriuretic peptide
- receiver-operating characteristic
- single-photon emission computed tomography
- 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid
- Received December 6, 2017.
- Revision received February 7, 2018.
- Accepted February 8, 2018.
- 2018 American College of Cardiology Foundation
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