Utility of Echocardiogram and Electrocardiogram in the Prediction of TTR Amyloid Diagnosed by Tc-Pyrophosphate SPECT Imaging

Abstract

Introduction Cardiac transthyretin amyloidosis (ATTR) results from myocardial deposition of insoluble TTR fibril proteins. In contrast to AL cardiac amyloidosis, there are no blood or urine tests to aid in the diagnosis. In clinical practice, ATTR is most commonly suspected when there is unexplained heart failure with preserved ejection fraction (HFpEF), left ventricular hypertrophy (LVH) on transthoracic echocardiogram (TTE), along with low voltage criteria on electrocardiogram (ECG). Definitive diagnosis historically required invasive endomyocardial biopsy, however technetium pyrophosphate (Tc-PYP) scans have recently emerged as a highly useful non-invasive test in the diagnosis of ATTR. We sought to examine the predictive value of multiple ECG and TTE parameters in the diagnosis of Tc-PYP positive ATTR. Methods We performed a retrospective chart review of 34 consecutive patients during January 2017-April 2018 at Scripps Clinic who underwent Tc-PYP scanning for clinically suspected ATTR. Patients were then separated into Tc-PYP positive and negative groups, and ECG and TTE obtained closest to the scan were reviewed. Statistical significance was determined by Mann-Whitney U and Fischer Exact test. Results Twenty patients had Tc-PYP positive scans versus 11 patients with Tc-PYP negative scans. Three patients with “equivocal” reads were excluded from the analysis. Overall no ECG parameters were significantly predictive of Tc-PYP+ scans. Rates of “low voltage” ECGs were similar between both groups (3/11 vs. 1/8, p-NS), and while there was a trend towards lower occurrence of sinus rhythm (5/20 vs. 5/11, p-NS) and increased ventricular-paced rhythms in patients with Tc-PYP+ scans (9/20 vs. 3/11, p-NS), these were not statistically significant. Comparing TTE variables, we found that Tc-PYP+ patients had significantly higher LV mass index values (171 vs. 123, p = 0.026) compared to Tc-PYP- patients. Additional TTE parameters (listed in Table) did not demonstrate any statistical significance. Conclusion In this single center study, we demonstrated that routinely used ECG and TTE parameters in clinical practice such as low voltage ECG and Tissue Doppler velocities lack sensitivity in the prediction of TTR Amyloid by Tc-PYP scans. Of various echocardiographic parameters, only LV mass index was statistically significant in predicting Tc-PYP positive scans. With promising new therapies on the horizon, and the emergence of Tc-PYP SPECT imaging as a highly specific noninvasive imaging modality for the diagnosis of ATTR, clinicians should have a high index of suspicion and should not stop with a TTE or ECG as both modalities lack sensitivity.