Author + information
- Received January 22, 2014
- Revision received March 7, 2014
- Accepted March 11, 2014
- Published online May 1, 2014.
- Arnt V. Kristen, MD∗∗ (, )
- Katrin Scherer, MS∗,
- Sebastian Buss, MD∗,
- Fabian aus dem Siepen, MS∗,
- Sabine Haufe, MD†,
- Ralf Bauer, MD∗,
- Katrin Hinderhofer, PhD‡,
- Evangelos Giannitsis, MD∗,
- Stefan Hardt, MD∗,
- Uwe Haberkorn, MD†,
- Hugo A. Katus, MD∗ and
- Henning Steen, MD∗
- ∗Department of Cardiology, Angiology, and Respiratory Medicine, University Hospital Heidelberg, Heidelberg, Germany
- †Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany
- ‡Institute of Human Genetics, University Hospital Heidelberg, Heidelberg, Germany
- ↵∗Reprint requests and correspondence:
Dr. Arnt V. Kristen, Department of Cardiology, Angiology, and Respiratory Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany.
Objectives We sought to evaluate noninvasive parameters by electrocardiography, echocardiography, technetium-99m–3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy, and cardiac magnetic resonance for the prediction of all-cause mortality in patients with cardiac transthyretin amyloidosis (ATTR).
Background ATTR may present with highly variable symptoms, including polyneuropathy and cardiomyopathy, the latter being associated with a poor outcome. However, data on noninvasive risk stratification of ATTR are limited.
Methods A total of 70 patients with ATTR were evaluated by echocardiography, cardiac biomarkers, and 99mTc-DPD scintigraphy. Cardiac magnetic resonance was performed in 30 patients. Echocardiographic findings and plasma levels of biomarkers were correlated with results of quantitative analysis of scintigraphy using a region-of-interest technique (whole-body as well as heart tracer retention). Receiver-operating characteristic (ROC) analysis was performed to calculate a cutoff value of 99mTc-DPD scintigraphy for heart retention for the diagnosis of cardiac amyloid involvement with the highest sensitivity and specificity. Univariate and multivariate analyses were performed in patients with cardiac involvement (n = 60) to determine noninvasive predictors of all-cause mortality.
Results Scintigraphy findings correlated with morphological (interventricular septum thickness, left ventricular hypertrophy index) as well as functional (mitral annular systolic velocity, mitral/tricuspid annular plane systolic excursion) findings, cardiac biomarkers, renal function, and late gadolinium enhancement. The ROC-derived cutoff for the detection of cardiac amyloidosis by scintigraphic heart tracer retention was 4.8%. Univariate Cox regression revealed N-terminal pro–B-type natriuretic peptide, troponin T, mitral annular plane systolic excursion, and left ventricular hypertrophy index as predictors of all-cause mortality. However, on multivariate analysis, troponin T remained the only independent predictor of survival. The ROC-derived cutoff value of troponin T predicting all-cause mortality with the highest sensitivity (80.0%) and specificity (68.7%) was 0.0375 ng/l.
Conclusions Quantitative analysis of tracer retention is capable of characterizing the severity of cardiac involvement in ATTR. By multivariate analysis, troponin T remained the only independent predictor of survival.
Dr. Giannitsis has received research support and honoraria from Roche Diagnostics. Dr. Katus has developed the cTNT assay and holds a joint patent with Roche Diagnostics, Germany; and he has received research support and honoraria for lectures from Roche Diagnostics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received January 22, 2014.
- Revision received March 7, 2014.
- Accepted March 11, 2014.
- American College of Cardiology Foundation