Deep learning to diagnose cardiac amyloidosis from CMR findings

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Aimo ◽  
N Martini ◽  
A Barison ◽  
D Della Latta ◽  
A Ripoli ◽  
...  

Abstract Background Cardiac magnetic resonance (CMR) is an important diagnostic technique for cardiac amyloidosis (CA). A deep learning (DL) approach to define the likelihood of CA based on automated interpretation of CMR images has never been attempted so far. Methods 187 subjects underwent standard 1.5 T CMR examination (GE-Healthcare, Milwaukee, USA) as part of a diagnostic workup for either unexplained left ventricular hypertrophy or blood dyscrasia with suspected light-chain (AL) amyloidosis. Patients were randomly assigned to 3 subgroups, which were used for training (n=121, 65%), internal validation (n=28, 15%), and model testing (n=38, 20%). LGE images in different orientations (short-axis, 2- and 4-chambers) were selected as the most informative CMR features. A deep convolutional neural network was trained to classify CMR examinations as “amyloidosis” (probability ≥50%) or “no amyloidosis” (probability <50%) based on these features. Different learning strategies (data augmentation, batch normalization in convolutional layers, dropout before dense layers) were adopted to prevent model overfitting. Binary cross entropy was used as loss function. For comparison, a machine learning (ML) model based on gradient boosting trees was built for the binary classification of patients (amyloidosis vs no amyloidosis) based on clinical and imaging features extracted from the CMR exam. Results CA was diagnosed in 101 subjects (54%; 45 AL, 56 transthyretin amyloidosis). A model including 2C, 4C and SA LGE images was created. In the test cohort, it allowed to diagnose CA with good diagnostic accuracy (84.2%), and an area under the curve (AUC) of 0.96 (Figure). The precision (positive predictive value), recall score (sensitivity), and F1 score (a measure of test accuracy) were 0.78, 0.94, and 0.86, respectively. An ML algorithm considering all available parameters (LV volumes and function, LGE presence and pattern, early darkening, pericardial and pleural effusion, etc.) displayed a similar diagnostic performance than the DL method (AUC 0.93 vs. 0.96; p=0.45). Conclusions The deep learning technique allowed to create an accurate diagnostic tool for CA based on LGE patterns, which could be easily converted into an online platform for automated image analysis. Funding Acknowledgement Type of funding source: None

2020 ◽  
Vol 22 (Supplement_N) ◽  
pp. N116-N130
Author(s):  
Alberto Aimo ◽  
Nicola Martini ◽  
Andrea Barison ◽  
Daniele Della Latta ◽  
Giuseppe Vergaro ◽  
...  

Abstract Aims Cardiac magnetic resonance (CMR) is part of the diagnostic work-up for cardiac amyloidosis (CA). Deep learning (DL) is an application of artificial intelligence that may allow to automatically analyze CMR findings and establish the likelihood of CA. Methods and results 1.5 T CMR was performed in 187 subjects with suspected CA (n = 92, 49% with unexplained left ventricular—LV—hypertrophy; n = 95, 51% with blood dyscrasia and suspected light-chain amyloidosis). Patients were randomly assigned to the training (n = 121, 65%), validation (n = 28, 15%), and testing subgroups (n = 38, 20%). Short axis (SA), 2-chamber (2 C), 4-chamber (4 C) late gadolinium enhancement (LGE) images were evaluated by 3 networks (DL algorithms). The tags “amyloidosis present” or “absent” were attributed when the average probability of CA from the 3 networks was ≥50% or < 50%, respectively. The DL strategy was compared to a machine learning (ML) algorithm considering all manually extracted features (LV volumes, mass and function, LGE pattern, early blood-pool darkening, pericardial and pleural effusion, etc.), to reproduce exam reading by an experienced operator. The DL strategy displayed good diagnostic accuracy (84%), with an area under the curve (AUC) of 0.96. The precision (positive predictive value), recall score (sensitivity), and F1 score (a measure of test accuracy) were 78%, 94%, and 86% respectively. A ML algorithm considering all CMR features had a similar diagnostic yield to DL strategy (AUC 0.93 vs. 0.96; p = 0.45). Conclusion A DL approach evaluating LGE acquisitions displayed a similar diagnostic performance for CA to a ML-based approach, which simulates CMR reading by experienced operators.


2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Nicola Martini ◽  
Alberto Aimo ◽  
Andrea Barison ◽  
Daniele Della Latta ◽  
Giuseppe Vergaro ◽  
...  

Abstract Background Cardiovascular magnetic resonance (CMR) is part of the diagnostic work-up for cardiac amyloidosis (CA). Deep learning (DL) is an application of artificial intelligence that may allow to automatically analyze CMR findings and establish the likelihood of CA. Methods 1.5 T CMR was performed in 206 subjects with suspected CA (n = 100, 49% with unexplained left ventricular (LV) hypertrophy; n = 106, 51% with blood dyscrasia and suspected light-chain amyloidosis). Patients were randomly assigned to the training (n = 134, 65%), validation (n = 30, 15%), and testing subgroups (n = 42, 20%). Short axis, 2-chamber, 4-chamber late gadolinium enhancement (LGE) images were evaluated by 3 networks (DL algorithms). The tags “amyloidosis present” or “absent” were attributed when the average probability of CA from the 3 networks was ≥ 50% or < 50%, respectively. The DL strategy was compared to a machine learning (ML) algorithm considering all manually extracted features (LV volumes, mass and function, LGE pattern, early blood-pool darkening, pericardial and pleural effusion, etc.), to reproduce exam reading by an experienced operator. Results The DL strategy displayed good diagnostic accuracy (88%), with an area under the curve (AUC) of 0.982. The precision (positive predictive value), recall score (sensitivity), and F1 score (a measure of test accuracy) were 83%, 95%, and 89% respectively. A ML algorithm considering all CMR features had a similar diagnostic yield to DL strategy (AUC 0.952 vs. 0.982; p = 0.39). Conclusions A DL approach evaluating LGE acquisitions displayed a similar diagnostic performance for CA to a ML-based approach, which simulates CMR reading by experienced operators.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Fuguang Ji ◽  
Shuai Zhou ◽  
Zhangshuan Bi

The clinical characteristics and vascular computed tomography (CT) imaging characteristics of patients were explored so as to assist clinicians in diagnosing patients with atherosclerosis. 316 patients with atherosclerosis who were hospitalized for emergency treatment were treated with rapamycin (RAPA) in the hospital. A group of manually delineated left ventricular myocardia (LVM) on the patient’s coronary computed tomography angiography (CCTA) were selected as the region of interest for imaging features extracted. The CCTA images of 80% of patients were randomly selected for training, and those of 20% of patients were used for verification. The correlation matrix method was used to remove redundant image omics features under different correlation thresholds. In the validation set, CCTA diagnostic parameters were about 40 times higher than the manually segmented data. The average dice similarity coefficient was 91.6%. The proposed method also produced a very small centroid distance (mean 1.058 mm, standard deviation 1.245 mm) and volume difference (mean 1.640), with a segmentation time of about 1.45 ± 0.51 s, compared to about 744.8 ± 117.49 s for physician manual segmentation. Therefore, the deep learning model effectively segmented the atherosclerotic lesion area, measured and assisted the diagnosis of future atherosclerosis clinical cases, improved medical efficiency, and accurately identified the patient’s lesion area. It had great application potential in helping diagnosis and curative effect analysis of atherosclerosis.


EP Europace ◽  
2020 ◽  
Vol 22 (8) ◽  
pp. 1216-1223
Author(s):  
Eun-Jeong Kim ◽  
Benjamin B Holmes ◽  
Shi Huang ◽  
Ricardo Lugo ◽  
Asad Al Aboud ◽  
...  

Abstract Aims Cardiac amyloidosis (CA) is associated with increased mortality due to arrhythmias, heart failure, and electromechanical dissociation. However, the role of an implantable cardioverter-defibrillator (ICD) remains unclear. We conducted case-control study to assess survival in CA patients with and without a primary prevention ICD and compared outcomes to an age, sex, and device implant year-matched non-CA group with primary prevention ICD. Methods and results There were 91 subjects with CA [mean age= 71.2 ± 10.2, female 22.0%, 49 AL with Mayo Stage 2.9 ± 1.0, 41 transthyretin amyloidosis (ATTR), 1 other] followed by Vanderbilt Amyloidosis centre. Patients with ICD (n = 23) were compared with those without (n = 68) and a non-amyloid group with ICD (n = 46). All subjects with ICD had implantation for primary prevention. Mean left ventricular ejection fraction was 36.2% ± 14.4% in CA with ICD, 41.0% ± 10.6% in CA without ICD, and 33.5% ± 14.4% in non-CA patients. Over 3.5 ± 3.1 years, 6 (26.1%) CA, and 12 (26.1%) non-CA subjects received ICD therapies (P = 0.71). Patients with CA had a significantly higher mortality (43.9% vs. 17.4%, P = 0.002) compared with the non-CA group. Mean time from device implantation to death was 21.8 months in AL and 22.8 months in ATTR patients. There was no significant difference in mortality between CA patients who did and did not receive an ICD (39.0% vs. 46.0%, P = 0.59). Conclusions Despite comparable event rates patients with CA had a significantly higher mortality and ICDs were not associated with longer survival. With the emergence of effective therapy for AL amyloidosis, further study of ICD is needed in this group.


2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
A M Brand ◽  
G Baldenhofer ◽  
D Frumkin ◽  
A Huebscher ◽  
K Stangl ◽  
...  

Abstract Background Echocardiographic hallmarks of cardiac amyloidosis (CA), such as increased wall thickness of the LV and sparkling appearance of the myocardium, are limited by a reduced diagnostic accuracy. Purpose We sought to evaluate the diagnostic value of phasic left atrial strain alterations and of regional global longitudinal systolic LV strain (LVGLS) reductions in patients with CA and with other forms of LV hypertrophy. Methods Standard apical 4-chamber views were stored for offline analysis (Vivid E9, GE, Vingmed, Horton) in 54 patients who underwent endomyocardial biopsy for unclear LV hypertrophy. We then analyzed LVGLS as well as LA reservoir, conduit, and contraction strain using 2D speckle tracking echocardiography (2DSTE; EchoPAC software, GE). To assess regional LVGLS, the average of apical strain values / (average of mid + basal LV strain values) was calculated (relative apical sparing; RELAPS). Receiver operating characteristic (ROC) curve analyses and a multivariate logistic regression analysis were performed to investigate the diagnostic value of the respective LA and LV deformation analysis. Results CA was bioptically confirmed in 34 patients (13 TTR, 1 AA, 20 AL amyloidosis). In 18 patients, myocardial biopsy revealed other forms of LV hypertrophy, such as hypertensive heart disease (n = 2), hypertrophic cardiomyopathy (n = 12), and inflammatory myocardial diseases (n = 4). Mean septal wall thickness (17.7 ± 2.9 mm and 17.9 ± 4.3 mm) and left atrial volume index (43.8 ± 12.2 and 44.1 ± 17.2) were not different between groups. RELAPS was significantly higher in patients with CA (1.37 ± 0.94 vs. 0.86 ± 0.29, p&lt;.007). Phasic atrial mechanics were significantly worse in CA (LA reservoir, conduit, and contraction strain 10.0 ± 5.2%, -6.5 ± 3.5%, and -5.0 ± 4.1%, respectively, in CA; and 22.7 ± 7.8%, -13.9 ± 5.2%, and -13.0 ± 5.5%, in LVH, respectively; p&lt;.001). With an area under the curve (AUC) of 0.91, and a sensitivity and specificity of 91.2 and 84.2% for a cut-off value of &lt;15.8%, LA reservoir strain showed a higher diagnostic accuracy in discriminating CA from LVH than the parameter RELPAS (AUC 0.74, sensitivity and specificity 60% and 71% for a cut-off of &gt;1.0; p&lt;.05). LA conduit and contraction strain performed significantly better than RELAPS as well (AUC 0.87 for conduit, and AUC 0.86 for contraction function; p&lt;.001 each). Of all echocardiographic parameters, LA reservoir strain remained significantly associated with CA in a multivariate regression model. Conclusions LA strain during all three phases of the atrial cycle was significantly reduced in patients with CA compared to other forms of LVH, and showed a markedly higher diagnostic accuracy than regional LV strain analysis, with LA reservoir strain showing highest discriminative value. The assessment of LA strain, as part of a comprehensive echocardiographic assessment, may be useful to rule-in the possible diagnosis of CA in patients with unclear LV hypertrophy.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Peter Huntjens ◽  
Kathleen Zhang ◽  
Yuko Soyama ◽  
Maria Karmpalioti ◽  
Daniel Lenihan ◽  
...  

Introduction: Light chain cardiac amyloidosis (AL) has a variable but usually poor prognosis. Left ventricular (LV) function measures including LV strain imaging for global longitudinal strain (GLS) have shown clinically prognostic value in AL. However, the utility of novel left atrial (LA) strain imaging and its associations with LV disease remains unclear. Hypothesis: LA strain is of additive prognostic value to GLS in AL. Methods: We included 99 consecutive patients with AL. Cardiac amyloidosis either confirmed by endocardial biopsy (25%) or by non-cardiac tissue biopsy and imaging data supportive of cardiac amyloidosis. Peak LA reservoir strain was calculated as an average of peak longitudinal strain from apical 2- and 4-chamber views. GLS and apical sparing ratio were assessed using the 3 standard apical views. All-cause mortality was tracked over a median of 5 years. Results: Echocardiographic GLS and peak longitudinal LA strain were feasible in 96 (97%) and 86 (87%) of patients, respectively. There were 48 AL patients who died during follow-up. Patients with low GLS (GLS < median; 10.3% absolute values) had worse prognosis than patients with high GLS group (p<0.001). Although peak longitudinal LA strain was correlated with GLS (R=0.65 p<0.001), peak longitudinal LA strain had additive prognostic value. AL patients with low GLS and low Peak LA strain (<13.4%) had a 8.3-fold increase in mortality risk in comparison to patients with high GLS (95% confidence interval: 3.84-18.03; p<0.001). Multivariable analysis showed peak longitudinal LA strain was significantly and independently associated with survival after adjusting for clinical and echocardiographic covariates (p<0.01). Conclusions: Peak longitudinal LA strain was additive to LV GLS in predicting prognosis in patients with biopsy confirmed AL amyloidosis. LA strain imaging has potential clinical utility in patients with AL cardiac amyloidosis.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Aimo ◽  
V Chubuchny ◽  
G Vergaro ◽  
M Fontana ◽  
M Nicol ◽  
...  

Abstract Background Early diagnosis of cardiac amyloidosis (CA) is warranted to initiate specific treatment and improve outcome. The amyloid light chain (AL) and inferior wall thickness (IWT) scores have been proposed to assess patients referred by hematologists or with unexplained left ventricular (LV) hypertrophy, respectively. These scores are composed of 4 or 5 variables, respectively, including strain data, and no decisional cut-offs were introduced. Methods Based on 2 variables common to the AL and IWT scores, we defined a simple score named AMYLoidosis Index (AMYLI) as the product of relative wall thickness (RWT) and E/e' ratio, and assessed its diagnostic performance. Optimal rule-out cut-offs were searched as those with negative likelihood ratio (LR−) &lt;0.1. Results In the derivation cohort (n=251), CA was ultimately diagnosed in 111 patients (44%). The 2.22 score value was selected as rule-out cut-off (LR- 0.0). In the hematology subset, AL CA was finally diagnosed in 32 patients (48%), with 2.36 as rule-out cut-off (LR− 0.0). In the hypertrophy subset, ATTR CA was diagnosed in 79 patients (43%), with 2.22 as best rule-out cut-off (LR− 0.0). In the validation cohort (n=691), where more patients were diagnosed with CA (94% and 68% in the hematology and in the hypertrophy subsets, respectively), the 2.22 rule-out cut-off had a LR− = ∞ (as no patient scoring &lt;2.22 had CA). In the hematology and hypertrophy subsets, the 2.36 and 2.22 cut-offs were effective for ruling-out CA, with both LR− = ∞ (as no patient scoring &lt;2.36 or 2.22, respectively, had CA). Conclusions The AMYLI score (RWT* E/e') is simpler than those proposed and similarly accurate. A 2.22 cut-off value excludes CA diagnosis in patients undergoing a diagnostic screening for CA, while a &lt;2.36 and a &lt;2.22 value may be better considered in the subsets with either blood dyscrasia or unexplained hypertrophy, respectively. Funding Acknowledgement Type of funding source: None


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
V Castiglione ◽  
A Aimo ◽  
A Barison ◽  
D Genovesi ◽  
C Prontera ◽  
...  

Abstract Background Cardiac amyloidosis (CA) is characterized by the accumulation of misfolded proteins into amyloid fibrils, leading to cardiomyocyte toxicity, extracellular volume expansion and ventricular pseudohypertrophy. As a consequence of such processes, natriuretic peptides and cardiac troponins are chronically elevated in CA and hold significant prognostic value. The diagnostic yield of these biomarkers for CA has never been explored so far. Methods Plasma levels of N-terminal fraction of pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) were measured in 230 patients referred to a tertiary centre with the clinical suspicion of cardiac amyloidosis. The final diagnosis was established according to current protocols, which include clinical, electrocardiographic, biohumoral, instrumental (echocardiography, cardiac magnetic resonance, diphosphonate scintigraphy), and biopsy examinations. Results Patients were aged 79 (interquartile interval 73–83) years and were predominantly males (n=147, 64%). Mean left ventricular (LV) ejection fraction was 55% (48–62%), and mean LV mass indexed was 150 (120–178) g/m2. CA was confirmed in 86 patients (37%), who had either light chain (AL) amyloidosis (n=25, 29%) or transthyretin (ATTR) amyloidosis (n=61, 71%). Alternative diagnoses were hypertensive cardiopathy (n=69, 48%), valvular disease (n=27, 19%), hypertrophic cardiomyopathy (n=18, 13%), or left ventricular hypertrophy with unknown or multifactorial mechanisms. Patients with CA showed higher NT-proBNP (5507 ng/L [2348–10326] vs. 1332 [392–3752], p<0.001) and hs-cTnT (65 ng/L [48–114] vs. 35 [21–52], p<0.001) than those without CA. The area under the curve (AUC) values for NT-proBNP and hs-cTnT were 0.712 and 0.775 respectively (p=0.062 for the difference). The combination of the two biomarkers improved discrimination over NT-proBNP alone (p=0.011), but not over hs-cTnT (p=0.470) (Figure). A NT-proBNP level <600 ng/L or a hs-cTnT level <17 ng/L were optimal for ruling out amyloidosis, with a negative predictive value of 95% in both cases. Patients with AL amyloidosis had higher NT-proBNP and hs-cTnT than those with ATTR (10809 ng/L [6292–17483] vs. 3084 [1841–7624], p=0.014; 130 ng/L [64–211] vs. 61 [48–95], p=0.006). The difference was even more prominent when biomarker levels were normalized for LV mass (NT-proBNP/LV mass, 33.9 ng/L/g [20.4–53.8] vs. 10.0 [5.8–23.5], p=0.002; hs-cTnT/LV mass, 0.48 ng/L/g [0.25–0.71] vs. 0.19 [0.14–0.26], p=0.001). NT-proBNP and hs-cTnT could effectively discriminate patients with AL amyloidosis among subjects with clinical suspicion of CA (AUC values of 0.787 and 0.805 respectively) (Figure). Figure 1 Conclusions Plasma NT-proBNP and hs-cTnT have diagnostic value in patients with suspected CA. In the subgroup with CA, both biomarkers are higher in patients with AL amyloidosis even when normalizing for LV mass, possibly because of a greater cardiotoxic effect of light-chain fibrils.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
K Stamatelopoulos ◽  
D Delialis ◽  
D Bampatsias ◽  
M E Tselegkidi ◽  
I Petropoulos ◽  
...  

Abstract Background The pattern of peripheral vascular involvement in the wild type transthyretin-related cardiac amyloidosis (ATTRwt) and its diagnostic utility in differentiating this infiltrating cardiomyopathy from light chain (AL) cardiac amyloidosis (AL-CA) and heart failure with preserved ejection fraction (HFpEF) of different origin have not been explored. Aims To characterize the pattern of peripheral vascular involvement in ATTRwt and evaluate its value in differentiating ATTRwt from AL-CA and HFpEF. Methods Newly diagnosed patients with ATTRwt (n=42) were consecutively recruited from our amyloidosis center. These patients were matched 1:1 for age and sex to patients with AL-CA (n=32) and subjects without amyloidosis (n=32) and also matched 2:1 to HFpEF patients (n=16). All subjects underwent a series of non-invasive vascular examinations for the assessment of: 1. subclinical carotid atherosclerosis with B-mode ultrasonography, 2. Arterial stiffness with measurement of carotid-femoral pulse wave velocity, 3. Reactive vasodilation with flow-mediated dilation (FMD) and 4. Aortic blood pressures and arterial wave reflections with augmentation index (AI) and return time of reflected wave (Tr). Results ATTRwt patients had lower peripheral (pBP) and aortic blood pressure (aBP) markers compared to non-AL controls (p&lt;0.05 for all). ATTRwt grouping was an independent determinant of these markers, after adjustment for cardiovascular risk factors (CVRF), including history of hypertension, hyperlipidemia and diabetes, glomerular filtration rate, body mass index and smoking status (core model). ATTRwt had lower aDBP and increased Tr compared to AL subjects. In a comparison between ATTRwt and AL patients with cardiac involvement, AI and Tr were higher and FMD lower in ATTRwt patients. ATTRwt was an independent determinant of these markers, after adjustment for the core model (p&lt;0.05 for all). Compared to HFpEF, patients with ATTRwt had lower peripheral and central BP and higher Tr (p&lt;0.05 for all). By ROC analysis, Tr provided high diagnostic value for ATTRwt vs. AL-CA (Area Under the Curve, AUC=0.809, CI: 0.65–0.96) and for ATTRwt vs combined AL-CA and HFpEF (AUC=0.880, CI: 0.79–0.97). Finally, AI was closely correlated with posterior (Spearman's Rho=−0.30) and intraventricular wall thickness (Rho=−0.329) and left ventricular global longitudinal strain (Rho=−0.4) and lower cDBP with higher Gilmore and New York Heart Association stage (p&lt;0.05). Conclusion ATTRwt patients present differential characteristics of peripheral vascular function and aortic hemodynamics as compared to AL, HFpEF and healthy controls. The clinical value of these characteristics merit further investigation since differential diagnosis among amyloidosis types is clinically challenging, while it may have prognostic implications. FUNDunding Acknowledgement Type of funding sources: None.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1500-1500
Author(s):  
Ashutosh D. Wechalekar ◽  
Helen J. Lachmann ◽  
Julian D. Gillmore ◽  
Philip N. Hawkins

Abstract Cardiac involvement in AL amyloidosis is associated with a poor prognosis and greatly increased treatment related morbidity and mortality, and regression of cardiac amyloid deposits is extraordinarily slow following chemotherapy that suppresses the underlying aberrant light chain production. Diagnosis of cardiac amyloidosis is normally made by echocardiography, by which time significant diastolic dysfunction has usually developed. Atrial natriuretic peptides (ANP, BNP and its N-terminal fragment NT-ProBNP) are useful in early diagnosis of myocardial dysfunction. Serum NT-ProBNP concentration has been reported to be a promising marker of cardiac dysfunction in AL amyloidosis, and patients with normal NT-ProBNP values at diagnosis have superior outcomes. We report here the outcome of patients attending the UK National Amyloidosis Centre (NAC) who had elevated NT-ProBNP at diagnosis of AL amyloidosis but who did not have accompanying evidence of cardiac involvement using conventional consensus criteria. To exclude the confounding effect of renal failure which is associated with substantial elevation of NT-ProBNP, we studied patients with serum creatinine &lt;150 μmol/L and creatinine clearance of &gt;50ml/min at diagnosis in whom there was less than 10% change in renal function after treatment. AL type amyloidosis was confirmed in all patients histologically with corroborating genetic studies to robustly exclude hereditary amyloidosis as indicated. Organ involvement and responses/progression were defined according to recent international consensus criteria (Gertz et al 2005). 102 patients who had no evidence of cardiac involvement by these conventional parameters and who otherwise conformed with our study criteria were identified. Median creatinine was 87 μmol/L (44–128), albumin 33g/L (10–65), bilirubin 7 μmol/L (1–65) and alkaline phosphatase 89 units/L (36–2649). The median interventricular septal and left ventricular posterior wall thickness was 9 mm (7–11 mm). 62 (61%) patients had NT-ProBNP ≤ 35pMol/L at diagnosis while 40 (39%) had NT-ProBNP of &gt;35 pMol/L. There was no significant difference in the baseline characteristics of either group. 5 patients in each group did not respond to the initial chemotherapy (p=0.46). With median follow-up of 60 months, 19/40 (47%) of patients with NT-ProBNP &gt;35pMol/L at diagnosis developed evidence of cardiac involvement compared to only 6/62 (10%) of whose baseline NT-ProBNP was ≤ 35 pMol/L (p&lt;0.001). The Kaplan-Meier estimated median overall survival has not been reached for either group but the estimated 7 year survival was significantly better in the group with NT-ProBNP of ≤35pMol/L compared to those with greater values (92% vs. 82%, p=0.03). In conclusion, these preliminary findings suggest that patients who have elevated NT-ProBNP concentration but no conventional evidence of cardiac involvement at diagnosis of AL amyloid appear to be at greater risk of developing cardiac amyloidosis during follow-up, and have a poorer prognosis. It reasonable to speculate that such patients have early cardiac involvement at diagnosis that cannot be identified by conventional non-invasive methods, and that their risk of subsequently developing clinically significant cardiac amyloidosis may be reduced by striving to achieve complete remission of their underling clonal plasma cell disease.


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