Relative Apical Sparing of Longitudinal Strain Using 2- Dimensional Speckle-Tracking Echocardiography is Both Sensitive and Specific for the Diagnosis of Cardiac Amyloidosis. Dr. Dermot Phelan MB BCh BAO PhD European Society of Cardiology 2012
None Disclosures
What is Amyloidosis? A group of disorders caused by abnormal folding, aggregation, and accumulation of amyloid fibrils in tissues Amyloid fibrils Deposits of amyloid fibrils progressively interfere with the structure/ function of affected organs Biochim Biophys Acta 2005;1753:11 Neth J Med 2004;62:104
Shah et al. Amyloidosis and the Heart. Arch Intern Med. 2006;166:1805-1813
Early diagnosis of cardiac amyloidosis (CA) is critical. Delay in diagnosis can mean patients are unsuitable for the most intensive treatment regimens. Survival in AL amyloid Untreated, median 12 months Clinical evidence of CCF, 4 to 6 months
Cardiac Amyloid: Characteristic Echo findings Concentric LV and RV wall thickening Biatrial dilation Restrictive filling pattern with low E Interatrial septal thickening Preserved EF early on with systolic dysfunction as disease progresses
JACC 2010;55:1769-79 HCM Amyloid HTN & renal failure Lysosomal storage disease Cardiac Oxalosis Frederich s Ataxia
Which patient has cardiac amyloidosis?
Strain Relative deformation of myocardium during the cardiac cycle - dimensionless Percent change in length compared to resting state (Strain (ε) = (L-L 0 )/ L 0 ) Can be measured regionally or globally L 0 L
Global longitudinal strain can be evaluated by frame by frame tracking of the speckles
Aim 1. To describe regional patterns in longitudinal strain (LS) using 2D speckle tracking echocardiography in cardiac amyloidosis (CA) 2. To test the hypothesis that regional differences would help differentiate CA from other causes of increased left ventricular (LV) wall thickness.
Methods
Methods - 1 Retrospective case-control study. 55 consecutive patients with confirmed CA were compared to 30 control patients matched for mean LV thickness [n=15 with hypertrophic cardiomyopathy (HCM), n=15 with aortic stenosis (AS)]. Longitudinal strain (LS) measurements were performed off-line by a reader blinded to the underlying diagnosis.
Methods - 2 Strain values for the 6 basal, 6 mid, and 6 apical segments of the left ventricle were averaged to obtain three regional LS values. The apex to base gradient in regional LS was examined using absolute strain values as well as a relative apical LS calculated as:
Statistical Analysis Comparisons across multiple groups 1 way analysis of variance (ANOVA) for parametric data and Kruskal-Wallis test for non-parametric data with post hoc analysis using Bonferroni correction. Comparisons between 2 groups independent samples t test or the Mann-Whitney Rank Sum test. Sensitivity and specificity of relative apical LS for the diagnosis of CA receiver operating characteristic (ROC) curves. Comparison ROC curves were derived to compare the area under the curve (AUC) To assess if relative longitudinal strain had additional predictive value to standard markers for detection of amyloid heart disease forward and backward logistic regression with multiple covariates diagnosis of amyloid as the outcome variable.
Results
Study Population Characteristics Variable CA (n=55) HCM (n=15) AS (n=15) P LVH (n=30) P Age (years) 68 ± 10 53 ± 12* 70 ± 15 <0.001 61 ± 16 0.04 Sex, (% male) 47 (85) 9 (60) 12 (80) 0.09 21 (70) 0.16 NYHA (mean) 2.48 ± 0.86 1.87 ± 0.99* 1.73 ± 0.88* 0.007 1.80 ± 0.92 0.002 Hypertension 27 (49) 11 (73) 13 (87) 0.02 23 (77) 0.01 Echo Parameters: Ejection Fraction (%) 47 ± 12 63 ± 5* 48 ± 14 <0.001 55 ± 13 0.003 MWT (mm) 16.9 ± 2.8 15.8 ± 3.6 15.7 ± 1.7 0.21 15.8 ± 2.7 0.07 LMVI (g/m 2 ) 149 ± 41 131 ± 46 160 ± 45 0.16 145 ± 47 0.70 LAVI (ml/m 2 ) 39.3 ± 10.1 40.0 ± 14.2 45.5 ± 13.3 0.053 42.2 ± 13.9 0.32 E (m/s) 0.86 ± 0.26 0.86 ± 0.27 1.0 ± 0.26 0.13 0.94 ± 0.27 0.20 E/A 2.20 ± 1.1 0.95 ± 0.3* 1.56 ± 0.8 <0.001 1.22 ± 0.65 <0.001 E/e 24.1 ± 12.7 15.3 ± 5.9* 20.3 ± 9.9 0.02 17.8 ± 8.4 0.008 DT m/s 183 ± 45 244 ± 64* 206 ± 65 0.001 226 ± 66 0.003 Global LS -8.9 ± 3.7-17.5 ± 3.4* -12.4 ± 3.8* <0.001-14.9 ± 4.4 <0.001 ECG Parameters: Low Voltage 21 (38) 0 (0)* 1 (7)* 0.002 1 (3) 0.001 Pseudoinfarct Pattern 16 (29) 2 (13) 3 (20) 0.41 5 (17) 0.31
Difference in Absolute Regional Longitudinal Strain between Groups. AS
Difference in Relative Regional Longitudinal Strain between Groups. 1
Comparison of receiver operating characteristic curves of both nondeformation and deformation echocardiographic parameters to diagnose cardiac amyloidosis.
Multivariable logistic regression analysis Outcome variable Diagnosis of Cardiac Amyloid Predictors Age, Gender, NYHA, History of hypertension or diabetes, EF, E/e, E/A, DT, Global LS, Peak gradient across the AV, Low voltage on ECG and Relative apical LS. Only a relative LS of 1 was significantly predictive of Cardiac Amyloid (p=0.004)
Representative 2D speckle tracking longitudinal strain patterns ( Bull s eye Plots ). CA CA CA CA HCM HCM AS AS
Conclusions Cardiac amyloid is characterized by regional variations in longitudinal strain from base to apex. A relative apical sparing pattern of longitudinal strain is an easily recognizable, accurate and reproducible method of differentiating CA from other causes of LV hypertrophy.
HHD HCM CA
Acknowledgements Dr. Jim Thomas Dr. Thomas Marwick Dr. Patrick Collier Dr. Dinesh Thavendiranathan Dr. Zoran Popovic Dr. Juan Carlos Plana Dr. Mazen Hanna
Thank You
Additional Slides
Variable CA (n=55) HCM (n=15) AS (n=15) P LVH (n=30) P Age (years) 68 ± 10 53 ± 12* 70 ± 15 <0.001 61 ± 16 0.04 Sex, (% male) 47 (85) 9 (60) 12 (80) 0.09 21 (70) 0.16 BMI (kg/m 2 ) 26 ± 6 30 ± 4* 29 ± 6 0.049 30 ± 5 0.004 BSA (m 2 ) 1.93 ± 0.26 2.07 ± 0.27 2.07 ± 0.23 0.07 2.07 ± 0.24 0.02 HR (bpm) 77 ± 14 67 ± 8* 69 ± 14* 0.01 68 ± 11 0.002 SBP (mmhg) 112 ± 21 130 ± 17* 132 ± 20* <0.001 131 ± 18 <0.001 DBP (mmhg) 69 ± 10 76 ± 11 71 ± 13 0.09 73 ± 12 0.08 NYHA (mean) 2.48 ± 0.86 1.87 ± 0.99* 1.73 ± 0.88* 0.007 1.80 ± 0.92 0.002 Hypertension 27 (49) 11 (73) 13 (87) 0.02 23 (77) 0.01 Hyperlipidemia 29 (53) 10 (67) 12 (80) 0.14 22 (73) 0.10 Diabetes Mellitus 9 (16) 7 (47) 6 (40) 0.02 13 (43) 0.01 Biochemical parameters: Hgb (g/dl) 12.5 ± 2.1 12.5 ± 2.1 10.2 ± 1.7* 0.001 11.1 ± 2.2 0.007 WCC 10 9 /l 7.8 ± 3.8 7.3 ± 2.5 7.8 ± 2.9 0.91 7.6 ± 2.7 0.80 Platelets 10 9 /l 206 ± 89 217 ± 116 200 ± 88 0.90 207 ± 99 0.97 Sodium (mmol/l) 137 ± 4 138 ± 3 137 ± 3 0.43 138 ± 3 0.50 Potassium (mmol/l) 4.1 ± 0.5 3.9 ± 0.5 4.4 ± 0.5 0.04 4.2 ± 0.6 0.50 BUN (mg/dl) 35 ± 22 19 ± 8* 26 ± 11 0.02 23 ± 10 0.008 Creatinine (mg/dl) 1.5 ± 0.8 1.7 ± 2.6 1.7 ± 2.2 0.90 1.7 ± 2.3 0.74 egfr (ml/min) 60 ± 31 104 ± 41* 79 ± 41 0.001 89 ± 42 <0.001 BNP (pg/ml) 536 (256:1474) 132.5 (37:283) NA <0.001
Variable CA HCM AS P LVH P Echo Parameters: Ejection Fraction (%) 47 ± 12 63 ± 5* 48 ± 14 <0.001 55 ± 13 0.003 MWT (mm) 16.9 ± 2.8 15.8 ± 3.6 15.7 ± 1.7 0.21 15.8 ± 2.7 0.07 LMVI (g/m 2 ) 149 ± 41 131 ± 46 160 ± 45 0.16 145 ± 47 0.70 LAVI (ml/m 2 ) 39.3 ± 10.1 40.0 ± 14.2 45.5 ± 13.3 0.053 42.2 ± 13.9 0.32 E (m/s) 0.86 ± 0.26 0.86 ± 0.27 1.0 ± 0.26 0.13 0.94 ± 0.27 0.20 A (m/s) 0.49 ± 0.27 0.94 ± 0.29* 0.70 ± 0.24* <0.001 0.84 ± 0.29 <0.001 E/A 2.20 ± 1.1 0.95 ± 0.3* 1.56 ± 0.8 <0.001 1.22 ± 0.65 <0.001 Average e (m/s) 4.2 ± 1.7 5.9 ± 1.7* 5.7 ± 2.0* <0.001 5.8 ± 1.8 <0.001 E/e 24.1 ± 12.7 15.3 ± 5.9* 20.3 ± 9.9 0.02 17.8 ± 8.4 0.008 DT m/s 183 ± 45 244 ± 64* 206 ± 65 0.001 226 ± 66 0.003 Global LS -8.9 ± 3.7-17.5 ± 3.4* -12.4 ± 3.8* <0.001-14.9 ± 4.4 <0.001 ECG Parameters: Low Voltage 21 (38) 0 (0)* 1 (7)* 0.002 1 (3) 0.001 Pseudoinfarct Pattern 16 (29) 2 (13) 3 (20) 0.41 5 (17) 0.31
Patient characteristics An endomyocardial biopsy proven diagnosis was available in 43/55 (78%) CA patients. Of the remaining 12 patients, 7 (13%) were diagnosed by a positive non-cardiac biopsy for amyloidosis with characteristic features on CMR while 5 (9%) had a positive non-cardiac biopsy for amyloidosis along with moderately increased LV wall thickness without a history of hypertension and a low voltage QRS on electrocardiogram.
AL amyloidosis n=27 TTR amyloidosis n=26 P AL Lambda n=19 AL Kappa n=8 P Mean Basal Strain (%) Mean Mid Strain (%) Mean Apical Strain (%) Mean Global Strain (%) -4.6 ± 3.8-3.3 ± 3.3 0.20-4.8 ± 3.5-4.2 ± 4.6 0.69-8.7 ± 4.1-7.0 ± 3.5 0.12-9.5 ± 3.7-6.8 ± 4.7 0.13-17.5 ± 5.2-14.5 ± 4.8 0.03-18.5 ± 5.3-15.1 ± 4.5 0.12-9.9 ± 3.9-7.9 ± 3.5 0.07-10.5 ± 3.6-8.3 ± 4.5 0.19 Mean relative Strain 1.9 ± 2.1 2.0 ± 1.4 0.90 1.5 ± 0.8 3.0 ± 3.6 0.10
Potential mechanism of apical sparing CMR data was available in 14/55 (25%) patients with CA and 9 /15 (60%) patients with HCM. Average basal, mid, and apical wall thickness in the CA subgroup was 1.66 ± 0.09cm, 1.58 ± 0.27cm and 0.81 ± 0.09cm respectively. When average wall thickness at these three ventricular levels were compared with reported normal values the average increase in the basal segments (111%) and midwall segments (122%) were significantly greater than the average increase in apical wall thickness (26%)
Reproducibility The intra-observer variability for measurement of LS in 272 measured segments showed an absolute bias between the two reads of 0.2 ± 4.2 (mean ± 2SD). The bias for inter-observer variability was 0.2 ± 5.2 (mean ± 2SD).