Cardiomyopathy
Usefulness of Combining Electrocardiographic and Echocardiographic Findings and Brain Natriuretic Peptide in Early Detection of Cardiac Amyloidosis in Subjects With Transthyretin Gene Mutation

https://doi.org/10.1016/j.amjcard.2015.07.008Get rights and content

Early noninvasive identification of cardiac amyloidosis (CA) is of growing clinical importance. Low voltage on electrocardiogram (ECG), increased left ventricular (LV) septal thickness (ST), and global longitudinal strain (GLS) on echocardiography, and elevated brain natriuretic peptides (BNP) are used as surrogates of CA. Thirty-five patients (50 ± 14 years, 22 women) underwent electrocardiography to analyze low-voltage QRS (<15 mV) pathologic Q waves, poor R-wave progression, ST-T abnormalities, and left bundle branch block. An ECG was considered abnormal if at least one ECG alteration was present. Echocardiography was used to analyze LVST, E/E′, and GLS. All participants also had BNP blood testing. 99mTc-3,3-diphosphono-1,2 propanodicarboxylic acid scintigraphy assumed as a reference method showed CA in 18 patients (51%, CA group) and no accumulation in 17 patients (no CA group). In descending order of accuracy, LVST >14 mm, E/E' >6.6, GLS <14.1, BNP >129 pg/ml, and an overall abnormal ECG showed good capability to distinguish patients with and without CA. All these parameters were predictors of CA in univariate analysis, whereas low-voltage QRS showed the worst performance. LVST >14 mm (p = 0.002) was the best independent predictor of CA, achieving sensitivity of 78% and accuracy of 89%. However, an LVST >14 mm (p = 0.005) plus an abnormal ECG (p = 0.03) show together a greater sensitivity, equal to 89%, in identifying CA. An integrated evaluation of ECG and echocardiography is a sensitive and low-cost technical approach to identify CA in patients with transthyretin gene mutation.

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Methods

We have included 36 consecutive patients with TTR-FAP belonging to 7 unrelated families. The study was approved by our institutional review committee. Informed consent was obtained from all patients.

Diagnosis was based on genetic testing for TTR-FAP: the Glu89Gln mutation was detected in 20 patients, the Phe64Leu mutation was detected in 12 patients, and the Thr49Ala mutation was detected in 4 patients. None of the included patients had evidence of monoclonal protein in the serum or urine, a

Results

Whole-body scan and SPECT revealed 99mTc-DPD accumulation (CA group) in 18 of 35 patients (51%) and no cardiac radiotracer accumulation (no CA group) in the remaining 17 patients (49%). In the CA group, cardiac 99mTc-DPD accumulation was graded as follows: grade 1, n = 6; grade 2, n = 8; grade 3, n = 4.

The age of patients in the CA group (52 ± 11 years) and no CA group (49 ± 14 years) was similar (p = 0.51). A higher prevalence of male sex (68% vs 6%, p <0.001) and somatic polyneuropathy (84%

Discussion

The main result of the present study is that an integrated approach consisting of ECG and echocardiography significantly increases sensitivity in diagnosing CA at an early stage in patients with FAP. In particular, we showed that the association between resting ECG abnormalities, consisting mainly of poor R-wave progression, pseudonecrosis, ST-T abnormalities, LBBB, low QRS voltage, and septal LV thickness (cut-off value 14 mm) on echocardiography was the most sensitive combination for the

Acknowledgments

The authors gratefully acknowledge Jennifer Pfaff, BA of Aurora Cardiovascular Services, Aurora St. Luke's Medical Center, for editorial preparation of the manuscript and Brian Miller and Brian Schurrer of Aurora Sinai Medical Center for help with the figures.

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