Elsevier

American Heart Journal

Volume 164, Issue 2, August 2012, Pages 222-228.e1
American Heart Journal

Clinical Investigation
Congestive Heart Failure
Prospective evaluation of the morbidity and mortality of wild-type and V122I mutant transthyretin amyloid cardiomyopathy: The Transthyretin Amyloidosis Cardiac Study (TRACS)

https://doi.org/10.1016/j.ahj.2012.04.015Get rights and content

Background

TRACS sought to describe the clinical outcomes and disease progression of transthyretin (TTR) cardiac amyloidosis (ATTR) in an observational study. Clinical course is largely determined by disease type with ATTR categorized as wild-type (ATTRwt) or genetic-variant protein (ATTRm). Prospective data are lacking in the most common TTR mutation, V122I, present in approximately 3.5% of African Americans.

Methods

Patients with ATTRwt (n = 18) and V122I ATTRm (n = 11) were longitudinally assessed every 6 months for up to 2 years by functional class assessments, biochemical markers, and echocardiography.

Results

At baseline, no differences in clinical characteristics, biomarkers, or echocardiographic parameters were noted between patients with ATTRwt and patients with ATTRm. After 15.5 ± 8 months, there were 11 deaths and 1 cardiac transplant, with higher mortality (73% vs 22%, P = .03) and cardiovascular hospitalization (64% vs 28%, P = .02) among patients with ATTRm. The median survival from diagnosis was 25.6 months for ATTRm vs 43.0 months for ATTRwt (P = .04). Univariate predictors of mortality included disease duration, heart rate ≥ 70 beats/min, baseline stroke volume, left ventricular ejection fraction < 50%, and ATTRm status. For each 6-month increment, the mean 6-minute walk distance declined by 25.8 m, N-terminal pro b-type natriuretic peptide increased by 1,816 pg/mL, and left ventricular ejection fraction fell by 3.2%, for the entire cohort.

Conclusions

In this prospective study, disease progression, morbidity, and mortality were observed in ATTR cardiomyopathy, particularly due to V122I, over a short duration. Given the prevalence of this mutation, further study of V122I in at-risk African American patients is warranted.

Section snippets

Study patients

Patients (n = 29) with ATTR cardiac amyloidosis associated with the V122I mutation (ATTRm; n = 11) or wild-type TTR (ATTRwt; n = 18) were identified after referral to tertiary care outpatient cardiology/amyloid clinics at participating sites. Eligibility and exclusion criteria are described more specifically in the supplemental materials to this study (see online Appendix, Study Patients).

Patients were studied at baseline and then at 6-month intervals for up to 2 years.

Biochemical and functional analysis

Blood samples were

Patient characteristics

Baseline characteristics of patients with ATTRm and ATTRwt demonstrated a high degree of similarity between the 2 groups in terms of gender, comorbidities, and baseline ECG findings (Table I). As expected, all patients with ATTRm were African American. Patients with ATTRwt tended to be older upon enrollment (76 ± 6 years vs 71 ± 5 years, P = .06), at the time of diagnosis (75 ± 6 years vs 70 ± 6 years), and upon symptom onset (73 ± 5 years vs 70 ± 6 years). Diastolic blood pressure was

Discussion

To our knowledge, TRACS represents the largest prospective, longitudinal study specifically designed to assess the natural history and disease progression of TTR cardiac amyloidosis due to both wild-type and, specifically, the V122I mutation. The principal finding of this report is that ATTR cardiomyopathy was associated with significant morbidity and mortality over a relatively short follow-up period of 15 months despite suggestions that heart disease in patients with ATTR, regardless of

Acknowledgements

The authors wish to acknowledge the General Clinical Research Unit (NIH M01 RR00533) of Boston University. Editorial support was provided by Xian Cao, MD, PhD at Scientific Strategy Partners and was funded by Pfizer Inc.

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