Comparison of right ventricular longitudinal strain imaging, tricuspid annular plane systolic excursion, and cardiac biomarkers for early diagnosis of cardiac involvement and risk stratification in primary systematic (AL) amyloidosis: a 5-year cohort study.

AIMS: To determine the role of assessing right ventricular (RV) function, using standard echocardiography and Doppler myocardial imaging (DMI), in the early diagnosis of cardiac amyloidosis and in the prediction of mortality. METHODS AND RESULTS: Patients with primary systemic (AL) amyloidosis seen at our institution from 1 February 2004 through 31 October 2005 (N=249) were categorized by left ventricular thickness and E' velocity and compared with 38 age- and sex-matched controls. Standard echocardiographic and DMI examination were used to measure echocardiographic parameters of RV function: systolic tissue velocity, strain rate, and strain were determined for basal and middle RV free wall segments. Patients were followed up for the endpoint of mortality. RV tricuspid annular plane systolic excursion (TAPSE) and all DMI measurements were lower in patients with AL amyloidosis and normal echocardiography results (AL-normal-echo group) than controls. A bivariate model including strain of the basal segment of the RV free wall and TAPSE was the best for distinguishing AL-normal-echo patients from controls. Male sex [hazard ratio (HR), 2.2; P=0.005], brain natriuretic peptide levels (HR 1.4; P=0.003), troponin T levels (HR 1.6; P=0.01), pleural effusion (HR 3.6; P<0.001), E/A ratio (HR 1.3; P=0.006), RV systolic pressure (HR 1.02; P=0.01), and RV strain rate of the middle segment (HR 1.3; P=0.02) were independent predictors of death. CONCLUSION: DMI measures of the RV can identify early impairment of cardiac function or stratify risk of death in patients with AL amyloidosis. Further studies with longer follow-up are warranted to confirm these results.

Utility of Doppler myocardial imaging, cardiac biomarkers, and clonal immunoglobulin genes to assess left ventricular performance and stratify risk following peripheral blood stem cell transplantation in patients with systemic light chain amyloidosis (Al).

BACKGROUND: Cardiac dysfunction is a well-recognized complication of light chain amyloidosis (AL). Autologous stem cell transplant (auto-SCT) has emerged as a successful treatment modality for AL patients. In this study, we examined the effect of clonal immunoglobulin light chain genes (VL), which encodes the immunoglobulin light chain protein that ultimately forms amyloid, on cardiac function, in the context of auto-SCT and its impact on overall survival. METHODS: Longitudinal Doppler myocardial imaging parameters along with cardiac biomarkers were used to assess for cardiac function pre and post auto-SCT. RESULTS: VL gene analysis revealed that Vl genes, in particular VlVI, were associated with worse cardiac function parameters than Vk genes. Clonal VL genes appeared to have an impact on left ventricular (LV) function post-transplant and also influenced mortality, with specific VL gene families associated with lower survival. Another key predictor of mortality in this report was change in tricuspid regurgitant flow velocity following auto-SCT. Correlations were also observed between systolic strain rate, systolic strain and VL genes associated with amyloid formation. CONCLUSIONS: Clonal VL gene usage influences global cardiac function in AL, with patients having VlVI and VlII-III-associated amyloid more severely affected than those having Vk or VlI amyloid. Pulsed wave tissue Doppler imaging along with immunoglobulin gene analysis offers novel insights into prediction of mortality and cardiac dysfunction in AL after auto-SCT.

Independent predictors of survival in primary systemic (Al) amyloidosis, including cardiac biomarkers and left ventricular strain imaging: an observational cohort study.

BACKGROUND: The prognostic value of Doppler myocardial imaging, including myocardial velocity imaging, strain, and strain rate imaging, in patients with primary (AL) amyloidosis is uncertain. The aim of this longitudinal study was to identify independent predictors of survival, comparing clinical data, hematologic and cardiac biomarkers, and standard echocardiographic and Doppler myocardial imaging measures in a cohort of patients with AL amyloidosis. METHODS: A total of 249 consecutive patients with AL amyloidosis were prospectively enrolled. The primary end point was all-cause mortality, and during a median follow-up period of 18 months, 75 patients (30%) died. Clinical and electrocardiographic data, biomarkers (brain natriuretic peptide and cardiac troponin T) and standard echocardiographic and longitudinal systolic and diastolic Doppler myocardial imaging measurements for 16 left ventricular segments were tested as potential independent predictors of survival. RESULTS: Age (hazard ratio [HR], 1.03; P = .03), New York Heart Association class III or IV (HR, 2.47; P = .01), the presence of pleural effusion (HR, 1.79; P = .08), brain natriuretic peptide level (HR, 1.29; P = .01), ejection time (HR, 0.99; P = .13), and peak longitudinal systolic strain of the basal anteroseptal segment (HR, 1.05; P = .02) were independent predictors in the final model. CONCLUSIONS: Multivariate survival analysis identified independent predictors of clinical outcome in patients with AL amyloidosis: New York Heart Association class III or IV, presence of pleural effusion, brain natriuretic peptide level > 493 pg/mL, ejection time < 273 ms, and peak longitudinal systolic basal anteroseptal strain less negative than or equal to -7.5% defined a high-risk group of patients.

Doppler myocardial imaging compared to standard two-dimensional and Doppler echocardiography for assessment of diastolic function in patients with systemic amyloidosis.

BACKGROUND AND AIMS: Cardiac amyloidosis (AL) is characterized by early impairment of diastolic function with preservation of systolic function, as assessed by standard measures, until very late in the disease process> Role of diastolic color Doppler myocardial imaging (cDMI), that is diastolic color Doppler myocardial velocity imaging (MVI) and strain rate imaging (SRI), to assess distolic dysfunction in this population remains unclear. METHODS: 238 patients with biopsy proven systemic primary (AL) amyloidosis and 39 age and sex-matched controls have been enrolled. Left ventricular diastolic cDMI measures were compared in patients and healthy subjects, to test if such diastolic dysfunction occurs before longitudinal left ventricular systolic dysfunction. RESULTS: Compared to Diastolic longitudinal, radial, and circumferential DMI, standard pulsed wave tissue Doppler imaging (PW-TDI) of the mitral annulus was the most accurate technique to detect early diastolic dysfunction in patients with AL. However, systolic longitudinal peak cDMI measures outperformed all of the diastolic measures, including PW-TDI, in separating patients with systemic AL, but no evidence of cardiac involvement on standard 2D and Doppler evaluation, from controls. CONCLUSIONS: Even when compared to diastolic cDMI measurements, standard PW-TDI of the mitral annulus was the most accurate diastolic measure to detect early left ventricular dysfunction in patients with AL amyloidosis. However, no diastolic measure approached the accuracy of longitudinal systolic cDMI measurements in identifying ventricular dysfunction in AL patients with normal standard 2D and Doppler examinations, compared to controls.

Evidence of impaired left ventricular systolic function by Doppler myocardial imaging in patients with systemic amyloidosis and no evidence of cardiac involvement by standard two-dimensional and Doppler echocardiography.

We examined the potential role of Doppler myocardial imaging for early detection of systolic dysfunction in patients with systemic amyloidosis (AL) but without evidence of cardiac involvement by standard echocardiography. We identified 42 patients without 2-dimensional echocardiographic or Doppler evidence of cardiac involvement. These patients had normal ventricular wall thickness and normal velocity of the medial mitral annulus. Myocardial images were obtained in these patients and in 32 age- and gender-matched healthy controls. Peak longitudinal systolic tissue velocity (sTVI), systolic strain rate (sSR), and systolic strain (sS) were determined for 16 left ventricular segments. Radial and circumferential sSR and sS were also measured. Compared with controls in this group of patients with AL, peak longitudinal sSR (-1.0 +/- 0.2 vs -1.4 +/- 0.2, p <0.001) and peak longitudinal sS (-15.6 +/- 3.3 vs -22.5 +/- 2.0 p <0.001) were significantly decreased. In conclusion, the mean sS from all 6 basal segments, or from all 16 left ventricular segments differentiated patients with AL with normal echocardiography from controls, with similar accuracy for the mean sSR from the 6 basal segments. This distinction was not apparent from peak longitudinal sTVI or from radial or circumferential sSI or sSR.

Detection of left ventricular systolic dysfunction in cardiac amyloidosis with strain rate echocardiography.

BACKGROUND: We examined the potential role of Doppler myocardial imaging including tissue velocity imaging, strain imaging, and strain rate imaging for detection of left ventricular systolic dysfunction in cardiac amyloidosis (CA) and determined the minimum dataset required to make the diagnosis. METHODS AND RESULTS: Doppler myocardial imaging was performed in 103 patients with amyloidosis (AL). Peak longitudinal systolic tissue velocity, systolic strain rate (sSR), and systolic strain (sS) were determined for 16 left ventricular segments. Radial and circumferential sSR and sS were also measured. Patients with increased left ventricular wall thickness were classified with advanced-CA, and the remainder of the patients were classified with AL-normal-wall-thickness. The global means of peak systolic tissue velocity (3.6 +/- 1.0 vs. 3.9 +/- 0.9, P = .007), sSR (-0.8 +/- 0.3 vs. -1.0 +/- 0.2, P < .001), and sS (-9.9 +/- 3.7 vs. -15.6 +/- 3.3, P < .001) were significantly lower in advanced-CA compared with AL-normal-wall-thickness. The mean of either sSR or sS from 6 middle or all 16 segments similarly differentiated patients with advanced-CA from AL-normal-wall-thickness. CONCLUSIONS: Longitudinal sS most accurately detects longitudinal systolic dysfunction in AL and best differentiates patients with advanced-CA with increased ventricular thickness from patients with AL-normal-wall-thickness. Interrogation of six middle segments was sufficient in identifying patients with advanced-CA. Further studies are warranted to define the incremental prognostic value of these new parameters in predicting outcomes for patients with AL.