18 F-FDG Uptake in Pancreatic AL Amyloidosis Associated With Multiple Myeloma.

ABSTRACT: A 60-year-old woman underwent whole-body contrast-enhanced CT because multiple myeloma was suspected. The contrast-enhanced CT showed pancreatic enlargement without main pancreatic duct dilatation and increased peripancreatic fat tissue. 18 F-FDG PET/CT demonstrated diffuse uptake in the enlargement of the pancreas, left and right ventricles, and vertebral column. Biopsy and bone marrow aspiration cytology revealed amyloid light-chain amyloidosis associated with multiple myeloma. Chemotherapy was performed; 18 F-FDG uptake in the pancreas then disappeared, and the pancreatic enlargement decreased. When diffuse 18 F-FDG uptake in pancreatic enlargement is observed in multiple myeloma patients, amyloid light-chain amyloidosis should be considered.

Clinical and imaging characteristics of patients with cardiac amyloidosis- a single center observational study.

Amyloidosis is a disease characterized by the deposition of protein fibrils. Cardiac involvement is a significant factor in determining prognosis. This study aimed to examine the clinical profile, outcomes, and long-term mortality rates in patients with transthyretin (ATTR) and amyloid light-chain (AL) amyloidosis. The retrospective cohort study included 94 patients with amyloidosis (69 with AL and 25 with ATTR amyloidosis) diagnosed between 2010 and 2022. The study involved multimodality imaging (ECG, echocardiography and cardiac magnetic resonance (CMR) data and survival analyses. Patients with ATTR amyloidosis were older and had a higher proportion of males compared to those with AL amyloidosis. Cardiac involvement was more prevalent in the ATTR group, including atrial fibrillation (AF), while pleural and pericardial effusion were more frequent in the AL group. Biomarkers such as NT-proBNP and troponin T were significantly elevated in both groups and were associated with all-cause mortality only in univariate analyses. CMR data, especially typical late gadolinium enhancement (LGE) was not associated with increased mortality, while pleural effusion and left atrial dilatation on echocardiography were identified as powerful predictors of mortality. In conclusion, both AL and ATTR amyloidosis exhibited poor outcomes. Cardiac involvement, particularly dilated left atrium and pleural effusion on echocardiography were associated with an increased risk of mortality, while typical LGE on CMR was not.

Light-Chain Cardiac Amyloidosis: Cardiac Magnetic Resonance for Assessing Response to Chemotherapy.

OBJECTIVE: Cardiac magnetic resonance (CMR) is a diagnostic tool that provides precise and reproducible information about cardiac structure, function, and tissue characterization, aiding in the monitoring of chemotherapy response in patients with light-chain cardiac amyloidosis (AL-CA). This study aimed to evaluate the feasibility of CMR in monitoring responses to chemotherapy in patients with AL-CA. MATERIALS AND METHODS: In this prospective study, we enrolled 111 patients with AL-CA (50.5% male; median age, 54 [interquartile range, 49-63] years). Patients underwent longitudinal monitoring using biomarkers and CMR imaging. At follow-up after chemotherapy, patients were categorized into superior and inferior response groups based on their hematological and cardiac laboratory responses to chemotherapy. Changes in CMR findings across therapies and differences between response groups were analyzed. RESULTS: Following chemotherapy (before vs. after), there were significant increases in myocardial T2 (43.6 ± 3.5 ms vs. 44.6 ± 4.1 ms; P = 0.008), recovery in right ventricular (RV) longitudinal strain (median of -9.6% vs. -11.7%; P = 0.031), and decrease in RV extracellular volume fraction (ECV) (median of 53.9% vs. 51.6%; P = 0.048). These changes were more pronounced in the superior-response group. Patients with superior cardiac laboratory response showed significantly greater reductions in RV ECV (-2.9% [interquartile range, -8.7%-1.1%] vs. 1.7% [-5.5%-7.1%]; P = 0.017) and left ventricular ECV (-2.0% [-6.0%-1.3%] vs. 2.0% [-3.0%-5.0%]; P = 0.01) compared with those with inferior response. CONCLUSION: Cardiac amyloid deposition can regress following chemotherapy in patients with AL-CA, particularly showing more prominent regression, possibly earlier, in the RV. CMR emerges as an effective tool for monitoring associated tissue characteristics and ventricular functional recovery in patients with AL-CA undergoing chemotherapy, thereby supporting its utility in treatment response assessment.

Quantification of right ventricular amyloid burden with 18F-florbetapir positron emission tomography/computed tomography and its association with right ventricular dysfunction and outcomes in light-chain amyloidosis.

AIMS: In systemic light-chain (AL) amyloidosis, quantification of right ventricular (RV) amyloid burden has been limited and the pathogenesis of RV dysfunction is poorly understood. Using 18F-florbetapir positron emission tomography/computed tomography (PET/CT), we aimed to quantify RV amyloid; correlate RV amyloid with RV structure and function; determine the independent contributions of RV, left ventricular (LV), and lung amyloid to RV function; and associate RV amyloid with major adverse cardiac events (MACE: death, heart failure hospitalization, cardiac transplantation). METHODS AND RESULTS: We prospectively enrolled 106 participants with AL amyloidosis (median age 62 years, 55% males) who underwent 18F-florbetapir PET/CT, magnetic resonance imaging, and echocardiography. 18F-florbetapir PET/CT identified RV amyloid in 63% of those with and 40% of those without cardiac involvement by conventional criteria. RV amyloid burden correlated with RV ejection fraction (EF), RV free wall longitudinal strain (FWLS), RV wall thickness, RV mass index, N-terminal pro-brain natriuretic peptide, troponin T, LV amyloid, and lung amyloid (each P < 0.001). In multivariable analysis, RV amyloid burden, but not LV or lung amyloid burden, predicted RV dysfunction (EF P = 0.014; FWLS P < 0.001). During a median follow-up of 28 months, RV amyloid burden predicted MACE (P < 0.001). CONCLUSION: This study shows for the first time that 18F-florbetapir PET/CT identifies early RV amyloid in systemic AL amyloidosis prior to alterations in RV structure and function. Increasing RV amyloid on 18F-florbetapir PET/CT is associated with worse RV structure and function, predicts RV dysfunction, and predicts MACE. These results imply a central role for RV amyloid in the pathogenesis of RV dysfunction.

Speckle tracking echocardiography in plasma cell disorders: The role of advanced imaging in the early diagnosis of AL systemic cardiac amyloidosis.

INTRODUCTION: Amyloid light-chain amyloidosis is a rare condition characterized by the abnormal production of immunoglobulin light chain that misshape and form amyloid fibrils. Over time, these amyloid deposits can accumulate slowly, causing dysfunction in organs and tissues. Early identification is crucial to ensure optimal treatment. We aim to identify a better marker of cardiac amyloidosis, using advanced echocardiography, to improve diagnosis and the timing of available treatments. MATERIALS AND METHODS: 108 consecutive hematological patients (32, 30% female and 76, 70% male) with a plasma cell disorder referred to our Cardiological center underwent ECG, first and second-level echocardiography (Speckle Tracking) and complete biochemical profile. The best predictors of ALCA (AUC ≥ 0.8) were included in a further analysis stratified by AL score. RESULTS: At ROC analysis, the best bio-humoral predictors for the diagnosis of ALCA were Nt-pro-BNP (AUC: 0.97; p < 0.01) and Hs-Tn (AUC: 0.87; p < 0.01). Regarding echocardiography, the best diagnostic predictors were left atrial stiffness (LAS) (AUC: 0.83; p < 0.01) for the left atrium; free wall thickness for the right ventricle (AUC: 0.82; <0.01); left ventricular global longitudinal strain (LVGLS) (AUC: 0.92; p < 0.01) and LVMi (AUC 0.80; p < 0.001) for the left ventricle; and AL-score (AUC 0.83 p < 0.01). In patients with AL-SCORE < 1, LAS (AUC 0.86 vs AUC 0.79), LVGLS (AUC 0.92 vs AUC 0.86) and LV mass (AUC 0.91 vs AUC 0.72) had better diagnostic accuracy than patients with higher AL-score (AL SCORE ≥ 1). CONCLUSION: Multi-parametric imaging approach with LVGLS and LAS may be helpful for detecting early cardiac involvement in AL amyloidosis.

Left ventricular myocardial work improves in response to treatment and is associated with survival among patients with light chain cardiac amyloidosis.

AIMS: Complete haematologic response to treatment for light chain cardiac amyloidosis (AL-CA) may lead to improvement of myocardial function and better outcomes. We sought to evaluate the effect of response to treatment for AL-CA on echocardiographic indices of myocardial deformation and work and their prognostic significance. METHODS AND RESULTS: Sixty-one patients treated for AL were enrolled and underwent echocardiographic assessment at baseline and at 1 year. Patients were stratified according to haematologic response as complete or not complete responders. A significant reduction in median N-terminal pro-brain natriuretic peptide (NT-proBNP) (2771-1486 pg/mL; P < 0.001) and posterior wall thickness (13-12 mm; P = 0.002) and an increase in global work index (GWI) (1115-1356 mmHg%; P = 0.018) was observed at 1 year. Patients with complete response (CR) had a more pronounced decrease in intraventricular septum thickness (14.2-12.0 mm; P = 0.006), improved global longitudinal strain (GLS) (-11.6 to -13.1%; P for interaction = 0.045), increased global constructive work (1245-1436 mmHg%; P = 0.008), and GWI (926-1250 mmHg%, P = 0.002) compared with non-CR. Furthermore, deltaGLS (ρspearman = 0.35; P < 0.001) and deltaGWI (ρspearman = -0.32; P = 0.02) correlated with delta NT-proBNP. Importantly, patients with GLS and GWI response had a better prognosis (log-rank P = 0.048 and log-rank P = 0.007, respectively). After adjustment for Mayo stage, gender, and response status, deltaGLS [hazard ratio (HR) = 1.404, P = 0.046 per 1% increase] and deltaGWI (HR = 0.996, P = 0.042 per 1mmHg% increase) were independent predictors of survival. CONCLUSION: Complete haematologic response to treatment is associated with improved left ventricular myocardial work indices, and their change is associated with improved survival in AL-CA.

Rare Forms of Cardiac Amyloidosis: Diagnostic Clues and Phenotype in Apo AI and AIV Amyloidosis.

BACKGROUND: Apo AI amyloidosis (AApoAI) and Apo AIV amyloidosis (AApoAIV) are rare but increasingly recognized causes of cardiac amyloidosis (CA). We sought to define the cardiac phenotype in AApoAI and AApoAIV using multimodality imaging. METHODS: We identified all patients with AApoAI and AApoAIV assessed at our center between 2000 and 2021, and 2 cohorts of patients with immunoglobulin light-chain amyloidosis (AL) and transthyretin amyloidosis matched for age, sex, and cardiac involvement. RESULTS: Forty-five patients had AApoAI, 13 (29%) of whom had cardiac involvement, 32 (71%) renal involvement, 28 (62%) splenic involvement, 27 (60%) hepatic involvement, and 7 (16%) laryngeal involvement. AApoAI-CA commonly presented with heart failure (n=8, 62%) or dysphonia (n=7, 54%). The Arg173Pro variant universally caused cardiac and laryngeal involvement (n=7, 100%). AApoAI-CA was associated with right-sided involvement, with a thicker right ventricular free wall (8.6±1.9 versus 6.3±1.3 mm versus 7.7±1.2 mm, P=0.004), greater incidence of tricuspid stenosis (4 [31%] versus 0 [0%] versus 0 [0%], P=0.012) and tricuspid regurgitation (6 [46%] versus 1 [8%] versus 2 [15%], P=0.048) than AL-CA and transthyretin CA. Twenty-one patients had AApoAIV, and cardiac involvement was more common than in AApoAI (15 [71%] versus 13 [29%], P=0.001). AApoAIV-CA most commonly presented with heart failure (n=12, 80%), and a lower median estimated glomerular filtration rate than AL-CA and transthyretin CA (36 mL/[min·1.73 m²] versus 65 mL/[min·1.73 m²] versus 63 mL/[min·1.73 m²], P<0.001). All AApoAIV-CA patients had classical CA features on echocardiography/cardiac magnetic resonance, including an apical-sparing strain pattern, which was less common in AApoAI-CA (15 [100%] versus 7 [54%], P=0.003), whereas cardiac uptake on bone scintigraphy was less common in AApoAIV-CA than AApoAI-CA (all grade 1) (14% versus 82%, P<0.001). Patients with AApoAI and AApoAIV had a good prognosis (median survival >172 and >30 months, respectively), and a lower risk of mortality than matched patients with AL-amyloidosis (AL versus AApoAI: hazard ratio, 4.54 [95% CI, 2.02-10.14]; P<0.001; AL versus AApoAIV: hazard ratio, 3.07 [95% CI, 1.27-7.44]; P=0.013). CONCLUSIONS: Dysphonia, multisystem involvement, or right-sided cardiac disease should raise suspicion of AApoAI-CA. AApoAIV-CA presents most commonly with heart failure and always displays classical CA imaging features, mimicking common forms of CA. Both AApoAI and AApoAIV are associated with a good prognosis and a lower risk of mortality than matched patients with AL-amyloidosis.

AL amyloidosis presenting with isolated lumbosacral radiculoplexus neuropathy.

A 45-year-old man presented with an isolated sciatic mononeuropathy, which then evolved into a lumbosacral radiculoplexus neuropathy. His initial symptoms included lower limb pain, sensory disturbance and later weakness, without autonomic dysfunction. Neurophysiology suggested a postganglionic neuropathy. MR and ultrasound scans of the thighs showed right sciatic nerve thickening, and CSF analysis showed albuminocytological dissociation. Fluorodeoxyglucose positron emission tomography (FDG PET) was unremarkable. He then developed orthostatic symptoms and urinary disturbance, and was found to have an IgM paraprotein. Fat aspirate, cardiac and whole-body imaging found no amyloid deposition, and genetic testing for transthyretin amyloidosis was negative. A bone marrow biopsy was unremarkable. However, neuropathology review of a proximal, fascicular nerve biopsy identified a lambda chain-restricted plasma cell population with positive Congo red staining, leading to a diagnosis of peripheral nerve restricted amyloid light amyloidosis. We discuss the diagnostic approach to this case from the perspectives of neurology, neurophysiology, radiology and neuropathology.

Extensive cardiac FDG uptake in a patient with AL amyloidosis.

Cardiac AL amyloidosis is a medical emergency causing rapid deterioration of cardiac function; however, it remains to be a diagnostic challenge especially when presenting with unusual symptoms and clinical findings. We present case of a 44-year-old patient with typical angina, persistently elevated troponin and normal epicardial coronary arteries. He was initially treated for myocarditis due to chest pain with troponin rise. However, CMR finding of subendocardial enhancement, increased native T1 values as well as extensive diffuse FDG uptake on PET-CT also suggested inflammatory cardiac conditions. Rapid decline in LV function and clinical deterioration led to further investigations including serum free light chains and bone marrow biopsy which confirmed systemic AL amyloidosis. Although the pathophysiology of unusual FDG PET-CT findings remains unknown, marked myocardial FDG uptake might have been caused by various features that were associated with AL amyloidosis including myocardial cell toxicity/inflammation or microvascular dysfunction. Awareness of these features specific to AL amyloidosis among physicians and description of associated cardiac FDG uptake findings has a potential to aid early diagnosis.

Feasibility of 68Ga-Labeled Fibroblast Activation Protein Inhibitor PET/CT in Light-Chain Cardiac Amyloidosis.

BACKGROUND: Systemic amyloid light chain (AL) amyloidosis is the most common type of amyloidosis, leading to cardiomyocyte necrosis and interstitial fibrosis. Gallium-68-labeled fibroblast activation protein inhibitor 04 (68Ga-FAPI-04) has recently been introduced for imaging fibroblast activation in cardiac diseases. To date, cardiac fibroblast and cardiac amyloidosis (CA) phenotype activities have not been mapped. OBJECTIVES: The aim of this study was to evaluate the feasibility of 68Ga-FAPI-04 positron emission tomography (PET)/computed tomography (CT) in assessing AL CA. METHODS: Thirty consecutive patients (mean age: 59.1 ± 7.7 years; 20 men, 10 women) with biopsy-proven AL amyloidosis were enrolled prospectively (including 27 with AL CA and 3 without AL CA). All patients underwent 68Ga-FAPI-04 PET/CT (107.4 ± 26.5 MBq). Global standardized uptake values and left ventricular (LV) molecular volume were calculated in correlation to echocardiography (n = 30), cardiac magnetic resonance (n = 18), and clinical biomarkers. Subsequently, the patients were categorized as having patchy (PET-patchy), extensive (PET-extensive), and negative (PET-negative) patterns. RESULTS: Of all patients, 80% (24 of 30) showed increased LV uptake (PET-patchy [n = 4] vs PET-extensive [n = 20]), whereas 6 patients did not show visible myocardial uptake. Standardized uptake value ratio and LV molecular volume were significantly higher in the PET-extensive than the PET-patchy group (2.79 mL ± 1.22 mL vs 1.53 mL ± 0.66 mL [P = 0.045] and 198.3 mL ± 59.97 mL vs 127.8 mL ± 25.82 [P = 0.005], respectively). Additionally, 68Ga-FAPI-04 uptake was significantly correlated with clinical biomarkers (Mayo stage and N-terminal pro-brain natriuretic peptide), interventricular septal thickness, left ventricular ejection fraction (LVEF), LV end-systolic volume, extracellular volume, and LV global strain (P < 0.05). CONCLUSIONS: 68Ga-FAPI-04 PET/CT is feasible in detecting myocardial fibroblast activation in patients with AL CA in correlation with myocardial remodeling. It might provide complementary information on cardiac molecular characterization and staging of disease.

Potential clinical relevance of cardiac magnetic resonance to diagnose cardiac light chain amyloidosis.

BACKGROUND: While patients with cardiac transthyretin amyloidosis are easily diagnosed with bone scintigraphy, the detection of cardiac light chain (AL) amyloidosis is challenging. Cardiac magnetic resonance (CMR) analyses play an essential role in the differential diagnosis of cardiomyopathies; however, limited data are available from cardiac AL-Amyloidosis. Hence, the purpose of the present study was to analyze the potential role of CMR in the detection of cardiac AL-amyloidosis. METHODS: We included 35 patients with proved cardiac AL-amyloidosis and two control groups constituted by 330 patients with hypertrophic cardiomyopathy (HCM) and 70 patients with arterial hypertension (HT), who underwent CMR examination. The phenotype and degree of left ventricular (LV) hypertrophy and the amount and pattern of late gadolinium enhancement (LGE) were evaluated. In addition, global and regional LV strain parameters were also analyzed using feature-tracking techniques. Sensitivity and specificity of several CMR parameters were analyzed in diagnosing cardiac AL-amyloidosis. RESULTS: The sensitivity and specificity of diffuse septal subendocardial LGE in diagnosing cardiac AL-amyloidosis was 88% and 100%, respectively. Likewise, the sensitivity and specificity of septal myocardial nulling prior to blood pool was 71% and 100%, respectively. In addition, a LV end-diastolic septal wall thickness ≥ 15 mm had an optimal diagnostic performance to differentiate cardiac AL-amyloidosis from HT (sensitivity 91%, specificity 89%). On the other hand, a reduced global LV longitudinal strain (< 15%) plus apical sparing (apex-to-base longitudinal strain > 2) had a very low sensitivity (6%) in detecting AL-Amyloidosis, but with very high specificity (100%). CONCLUSIONS: The findings from this study suggest that CMR could have an optimal diagnostic performance in the diagnosis of cardiac AL-amyloidosis. Hence, further larger studies are warranted to validate the findings from this study.

Imaging-Guided Treatment for Cardiac Amyloidosis.

PURPOSE OF REVIEW: This review will explore the role of cardiac imaging in guiding treatment in the two most commonly encountered subtypes of cardiac amyloidosis (immunoglobulin light-chain amyloidosis [AL] and transthyretin amyloidosis [ATTR]). RECENT FINDINGS: Advances in multi-parametric cardiac imaging involving a combination of bone scintigraphy, echocardiography and cardiac magnetic resonance imaging have resulted in earlier diagnosis and initiation of treatment, while the evolution of techniques such as longitudinal strain and extracellular volume quantification allow clinicians to track individuals' response to treatment. Imaging developments have led to a deeper understanding of the disease process and treatment mechanisms, which in combination result in improved patient outcomes. The rapidly expanding treatment regimens for cardiac amyloidosis have led to an even greater reliance on cardiac imaging to help establish an accurate diagnosis, monitor treatment response and aid the adjustment of treatment strategies accordingly.

Multi-parametric speckle tracking analyses to characterize cardiac amyloidosis: a comparative study of systolic left ventricular longitudinal myocardial mechanics.

Cardiac amyloidosis (CAM), the most common cardiac storage disease is associated with significant changes in left-ventricular (LV) morphology and function. To gain particular insights into LV systolic longitudinal myocardial mechanics we investigated seven parameters derived by speckle-tracking-echocardiography (STE) in patients with confirmed CAM (n = 59). The results were compared with those of individuals with healthy heart (n = 150) and another primary myocardial disease with also thickened myocardium and severe diastolic and systolic LV-dysfunction (symptomatic LV-non-compaction-cardiomyopathy, LV-NC, n = 30). In addition to standard echocardiographical measures, the STE-derived data were evaluated and documented utilizing polar-diagrams to obtain overviews of longitudinal myocardial mechanics of the entire LV. Compared with healthy individuals, patients with CAM and LV-NC showed significantly reduced LV-ejection-fraction (EF), global longitudinal systolic peak-strain, strain-rate, and displacement. Pre-systolic stretch-index, post-systolic index, and the EF/global peak-longitudinal-strain-ratio (EF/S) were increased. In contrast to healthy-hearts and the LV-NC group only patients with CAM demonstrated significantly reduced time-to-peak systolic longitudinal strain and time-to-peak strain-rate. Although the level of the segmental values in longitudinal mechanics was significantly different between the groups, comparable intraventricular baso-apical parameter-gradients were found for systolic longitudinal peak-strain and strain-rate, pre-systolic-stretch-index, post-systolic-index, and peak systolic displacement. Compared to ATTR-amyloidosis (ATTR-CAM), patients with AL-amyloidosis (AL-CAM) demonstrated significantly lower end-diastolic and end-systolic LV-volumes, LV-mass-indices, relative apical strain, time-to-peak systolic longitudinal strain, and time-to-peak longitudinal strain-rate. CAM and LV-NC demonstrated altered myocardial mechanics with significantly different STE-derived echocardiographical parameters. ATTR-amyloidosis and AL-amyloidosis had at least significantly different time-to-peak strain, time-to-peak strain-rate and relative apical sparing values.

Alterations in multi-layer strain in AL amyloidosis.

BACKGROUND: Cardiac involvement in AL amyloidosis portends a poor prognosis. 2D-speckle tracking echocardiography (2D-STE) strain can identify subclinical cardiac involvement. This study performed multilayer and multiplanar 2D-STE myocardial strain analysis. METHODS: We compared 75 AL amyloidosis patients to 49 hypertensive patients and 49 healthy controls. Longitudinal strain was obtained from epicardial, mid-myocardial and endocardial layers; segmental strain was measured from mid-myocardial basal, mid and apical segments. RESULTS: Global longitudinal strain was reduced in epicardial (-14.3 ± -4.0% vs. -17.4 ± 2.2% vs. -17.5 ± -2.0%, p < .001), mid-myocardial (-16.3 ± -4.5% vs. -19.7 ± 2.5% vs. -19.7 ± -2.2%, p < .001) and endocardial layers (-18.7 ± -4.9% vs. -22.2 ± 3.0% vs. -22.3 ± -2.6%, p < .001) in amyloid patients compared to hypertensive and healthy controls. Segmental strain confirmed significant reduction in basal (-11.2 ± -3.9% vs. -17.6 ± 2.7% vs. -20.9 ± -3.4%, p < .001) and mid (-14.8 ± -4.3% vs. -19.2 ± 2.5% vs. -19.6 ± -2.2%, p < .001) LV segments in the AL amyloid group. Receiver operating curve analysis demonstrated that an optimal cut-off of -16% for basal segmental strain better differentiated AL amyloid from hypertensive group (sensitivity 96%, specificity 70%, AUC 0.93), compared to relative apical sparing (AUC of 0.85). CONCLUSION: Strain demonstrated myocardial involvement in all layers in AL amyloidosis, with reduced basal segmental longitudinal strain a likely marker of early disease.

Atrial function and geometry differences in transthyretin versus immunoglobulin light chain amyloidosis: a cardiac magnetic resonance study.

To determine the differences in left atrial (LA) function and geometry assessed by cardiac magnetic resonance (CMR) between transthyretin (ATTR) and immunoglobulin light chain (AL) cardiac amyloidosis (CA). We performed a retrospective analysis of 54 consecutive patients (68.5% male, mean age 67 ± 11 years) with confirmed CA (24 ATTR, 30 AL) who underwent comprehensive CMR examinations. LA structural and functional assessment including LA volume, LA sphericity index, and LA strain parameters were compared between both subtypes. In addition, 15 age-matched controls were compared to all groups. Patients with ATTR-CA were older (73 ± 9 vs. 62 ± 10 years, p < 0.001) and more likely to be male (83.3% vs. 56.7%, p = 0.036) when compared to AL-CA. No significant difference existed in LA maximum volume and LA sphericity index between ATTR-CA and AL-CA. LA minimum volumes were larger in ATTR-CA when compared with AL-CA. There was a significant difference in LA function with worse strain values in ATTR vs AL: left atrial reservoir [7.4 (6.3-12.8) in ATTR vs. 13.8 (6.90-24.8) in AL, p = 0.017] and booster strains [3.6 (2.6-5.5) in ATTR vs. 5.2 (3.6-12.1) in AL, p = 0.039]. After adjusting for age, LA reservoir remained significantly lower in ATTR-CA compared to AL-CA (p = 0.03), but not LA booster (p = 0.16). We demonstrate novel differences in LA function between ATTR-CA and AL-CA despite similar LA geometry. Our findings of more impaired LA function in ATTR may offer insight into higher AF burden in these patients.

Myocardial Composition in Light-Chain Cardiac Amyloidosis More Than 1 Year After Successful Therapy.

OBJECTIVES: The goals of this study were to characterize myocardial composition during the active and remission phases of light-chain (AL) cardiac amyloidosis. BACKGROUND: Cardiac dysfunction in AL amyloidosis is characterized by dual insults to the myocardium from infiltration and toxicity from light chains during the active phase and by infiltration alone in the remission phase. METHODS: Prospectively enrolled subjects with cardiac AL amyloidosis (21 remission AL amyloidosis; age: 63.4 ± 7.3 years; 47.6% male; and 48 active AL amyloidosis; age: 62.5 ± 7.4 years; 60.4% male) underwent contrast-enhanced cardiac magnetic resonance with T1 and T2 mapping and measurement of extracellular volume (ECV). By definition, serum free light-chain levels were normal for at least 1 year following successful AL therapy in the remission group and abnormal in the active group. RESULTS: Myocardial ECV was similarly expanded in the remission and active AL amyloidosis groups (0.488 ± 0.082 vs 0.519 ± 0.083, respectively; P = 0.15). However, myocardial T2 relaxation times (47.7 ± 3.2 ms vs 45.5 ± 3.0 ms; P = 0.008) as well as native T1 times (1,368 ms [IQR: 1,290-1,422 ms] vs 1,264 ms [IQR: 1,203-1,380 ms]; P = 0.024) were significantly higher in the remission compared to the active AL amyloidosis group. CONCLUSIONS: Myocardial ECV is substantially expanded in the active AL and remission AL cardiac amyloidosis groups, but native T1 values were higher, suggesting a different myocardial composition. There is no evidence of myocardial edema in active AL cardiac amyloidosis. Future phenotyping studies of AL cardiac amyloidosis need to consider complementary myocardial markers that define the interstitial milieu in addition to changes in extracellular volume. (Molecular Imaging of Primary Amyloid Cardiomyopathy; NCT02641145).