Early Diagnosis of Cardiac Involvement in Hereditary Transthyretin Amyloidosis Urged

Based on the aging of the population, heart failure with preserved ejection fraction (HFpEF) is a common condition with a prevalence that is expected to increase. HFpEF is a common symptom of various underlying myocardial conditions. Combined with the dearth of benefits from current therapies across the HFpEF continuum, this etiological heterogeneous condition poses clinical challenges. Therefore, distinguishing the fundamental etiology of HFpEF is a critical aspect of improving patient management. A common cause of HFpEF is cardiac amyloidosis. Light-chain amyloidosis was believed to be the most frequent form, traditionally; yet recent studies have revealed otherwise.

The prevalence of cardiac ATTR (TTR-CA) in patients with HFpEF and left ventricular hypertrophy (LVH) ranges between 13% and 19%, based on scintigraphy imaging studies. The accumulation of amyloid fibrils in the myocardium with LVH proceeding in later stages marks the evolution of cardiac amyloidosis. It is possible to identify TTR-CA prior to the hypertrophic stage, based on current imaging modalities.

Devesa and colleagues investigated the prevalence of TTR-CA in HFpEF patients without LVH, by studying prospectively enrolled patients admitted for heart failure with left-ventricular ejection fraction (LVEF) ≥50% and left-ventricular wall thickness ATTR, which they found to be more prevalent.

A genetic (hereditary) form and a wild-type (sporadic) form, which is more frequent, are the 2 forms of TTR-CA that have been described.

Recent innovations in noninvasive imaging, specifically technetium-labeled cardiac scintigraphy, have enabled noninvasive diagnosis with high specificity.

The prevalence of wild-type TTR-CA is much greater than previously assessed, based on new noninvasive test results.

Due to the availability of approved treatments (ie, tafamidis) for TTR-CA, that prevent the deposition of amyloid in organs (eg, heart) but do not remove deposited fibrils, it is critical to initiate treatment early in the disease course to gain the greatest benefit in terms of inhibiting amyloid deposits.

Patients admitted for heart failure with LVEF ≥50% and left-ventricular wall thickness <12 mm were prospectively enrolled in the study. Positive cardiac 99-Tc-DPD scintigraphy, in the absence of monoclonal protein expansion in blood, was used to diagnose TTR-CA.

In positive patients, transthyretin gene sequencing was performed. In total, 329 patients with HFpEF and left-ventricular wall thickness <12 mm were identified from July 2017 to January 2020. In total, 58 patients met inclusion criteria and completed the study with cardiac scintigraphy. The average age was 79 years, 54% were men, and median LVEF was 60% and left-ventricular wall thickness was 10.5 mm.

In total, 5.2% of these patients were positive for TTR-CA; the presence of hereditary ATTR was excluded by genetic analysis. With the exception of troponin levels (0.05 ng/mL vs 0.02 ng/mL; P = .03) and glomerular filtration rate (82 mL/min vs 60 mL/min; P = .032), which were higher in the TTR patient cohort compared with patients without TTR-CA, positive patient baseline characteristics (84 years, 67% men, LVEF 60%, and left ventricular wall thickness 11 mm) were similar to patients without TTR-CA.

Based on the findings from this study, the prevalence of TTR-CA was 5% in a cohort of patients with HFpEF without LVH. Since newly approved treatments can specifically inhibit further deposition of amyloid material, early diagnosis of cardiac involvement in ATTR before LVH becomes apparent would seem to be advised.

Source: Devesa A, Camblor Blasco A, Pello Lázaro AM, et al. Prevalence of transthyretin amyloidosis in patients with heart failure and no left ventricular hypertrophy. ESC Heart Fail. 2021;8:2856-2865.

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