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Variant transthyretin amyloidosis is a systemic disease. In Sweden, the Val30Met variant is the most prevalent. Val30Met presents in two phenotypes: an early-onset form dominated by polyneuropathy and a late-onset form frequently accompanied by cardiomyopathy. These phenotypes are associated with two amyloid fibril types. Type A fibrils, contain both fragmented and full-length transthyretin, whereas type B fibrils contain only full-length transthyretin. Fibril type has been linked to differences in cardiac tracer uptake on 99mTc-DPD scintigraphy. A total of 152 patients with confirmed variant transthyretin amyloidosis evaluated at Umeå University Hospital, Sweden, were included. Age at disease onset and cardiac involvement, investigated by echocardiography, Troponin-T, and NT-proBNP, were assessed in relation to fibril type in abdominal fat and scintigraphic findings. Eighty-five patients had type A fibrils and sixty-seven had type B fibrils. Type A patients were older at diagnosis and had pathologic scintigraphies and more severe cardiac involvement. A subset of type B patients (15%) exhibited cardiac tracer uptake and had cardiac characteristics and age at disease onset similar to those with type A fibrils. Even though there was a strong correlation with findings in abdominal fat pad biopsies, results from 99mTc-DPD scintigraphy correlated better with clinical phenotype.

BACKGROUND: Cardiac amyloidosis is an underdiagnosed condition and simple methods for accurate diagnosis are warranted. We aimed to validate a novel, dual-modality approach to identify transthyretin cardiac amyloidosis (ATTR-CA), employing echocardiographic relative wall thickness (RWT), and ECG S-wave from aVR (SaVR), and compare its accuracy with conventional echocardiographic approaches.

MATERIAL AND METHODS: We investigated 102 patients with ATTR-CA and 65 patients with left ventricular hypertrophy (LVH), all with septal thickness > 14 mm. We validated the accuracy of echocardiographic measures, including RWT, RWT/SaVR, posterior wall thickness (PWT), LV mass index (LVMI), left atrial volume index (LAVI), global longitudinal strain (GLS), and relative apical sparing (RELAPS) to identify ATTR-CA diagnosed using DPD-scintigraphy or abdominal fat biopsy.

RESULTS: PWT, RWT, RELAPS, troponin, and RWT/SaVR were significantly higher in ATTR-CA compared to LVH. RWT/SaVR > 0.7 was the most accurate parameter to identify ATTR-CA (sensitivity 97%, specificity 90% and accuracy 91%). RELAPS was found to have much less accuracy (sensitivity 74%, specificity 76% and accuracy 73%).

CONCLUSION: We can confirm the very strong diagnostic accuracy of RWT/SaVR to identify ATTR-CA in patients with septal thickness > 14 mm. Given its high sensitivity and specificity, RWT/SaVR > 0.7 has the potential to implement as a non-invasive, simple, and widely available diagnostic tool when screening for ATTR-CA.

Purpose: Hereditary transthyretin-amyloid amyloidosis (ATTRv) is an underdiagnosed condition commonly manifesting as congestive heart failure. Recently, scintigraphy utilizing DPD as a tracer was shown to identify ATTRv and wild-type ATTR cardiomyopathy. The aim of this study was to determine the value of quantified scintigraphy utilizing ^99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) single-photon emission computed tomography (SPECT)/CT, and to correlate its uptake with well-established cardiac functional parameters.

Methods: Forty-eight patients with genetically verified ATTRv type-A fibril composition, positive ^99mTc-DPD SPECT/CT, were retrospectively analyzed. Manual mapping of volumes of interest (VOIs) on DPD SPECT/CT examinations was used to quantify heart uptake. DPD mean and maximum uptake together with a calculated DPD-based amyloid burden (DPD_load) was correlated with echocardiographic strain values and cardiac biomarkers.

Results: Statistically significant correlations were seen in VOIs between DPD uptakes and the corresponding echocardiographic strain values. Furthermore, DPD_load had a strong correlation with echocardiographic strain parameters and also correlated with biomarkers troponin T and logarithmic NT-ProBNP.

Conclusions: In patients with ATTRv cardiomyopathy, DPD SPECT/CT measures the amyloid distribution and provides information on cardiac amyloid load. DPD amyloid load correlates with functional cardiac parameters.

AIMS/BACKGROUND: Transthyretin amyloid (ATTR) amyloidosis cardiomyopathy is an underdiagnosed, causatively treatable cause of heart failure. The aim of this study was to evaluate the efficacy of electrocardiography (ECG) and echocardiography on patients with increased interventricular septum diameter (IVSd) to identify ATTR cardiac amyloidosis (ATTR-CA) patients.

METHODS: We investigated 58 patients with heart failure and an IVSd >14mm. Included were 33 ATTR-CA patients and 25 controls that consisted of non-amyloidosis heart failure (HF) patients with negative 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scintigraphy. We used echocardiography including 2D speckle tracking strain and a 12-lead ECG to test the accuracy to differentiate the groups.

RESULTS: We found high diagnostic accuracy (98%) for differentiating ATTR-CA from HF controls using a combination of R amplitude in -aVR from ECG and relative wall thickness acquired from echocardiography. With this combined model (RWT/ R in -aVR), the sensitivity was 100% and specificity was 95% using a cut off value of 0.90. Furthermore, the area under the curve was 99% and the negative predictive value was 100%.

CONCLUSION: We found that a simple combination of ECG and echocardiographic parameters used in clinical settings was able to differentiate ATTR-CA from other etiologies of HF with increased interventricular septum thickness. The high sensitivity and negative predictive value render the algorithm useful for selection of patients for further diagnostic procedures for ATTR-CA.