Circulating biomarkers in diagnosis and management of cardiac amyloidosis: a review for internist

Abstract

Cardiac amyloidosis (CA) is due to extracellular myocardial deposition of misfolded proteins resulting in severe cardiac dysfunction and death. The precursors of amyloid fibrils, able of determining a relevant cardiac infiltration, are immunoglobulin-free light chains (AL amyloidosis) and transthyretin (TTR) (both wild and mutated types). The diagnosis of amyloidosis represents a challenge for the clinician given its rarity and its protean clinical presentation, thus an early diagnosis remains a cornerstone for the prognosis of these patients, also in light of the growing available treatments. There is great interest in identifying and applying biomarkers to help diagnose, inform prognosis, guide therapy, and serve as surrogate endpoints in these patients. In AL amyloidosis, biomarkers such as free light chains, natriuretic peptides and troponins are the most extensively studied and validated; they have proved useful in risk stratification, guiding treatment choice and monitoring hematological and organ response. A similar biomarker-based prognostic score is also proposed for ATTR amyloidosis, although studies are small and need to be validated for wild-type and mutant forms. Graphical abstract

Early diagnostic and prognostic value of myocardial strain derived from cardiovascular magnetic resonance in patients with cardiac amyloidosis

“…Thus, there is a great unmet medical need for early diagnosis of amyloid cardiac involvement. Our study found that advanced NYHA grade, high BNP and myocardial injury markers, low eGFR, and high E/E' are all potential risk factors for poor prognosis and these factors also play an important role in staging the disease, guiding treatment and prognostic assessment ( 31 , 32 ), which is also consistent with current clinical knowledge. With regard to CMR, the important value of LGE in assessing the prognosis of CA patients has been reaffirmed.…”

A review of transthyretin cardiac amyloidosis

“…As such, early detection is paramount to prevent systemic complications and to initiate therapeutic interventions in a timely fashion. Amyloidosis workup is comprehensive with inclusion of clinical presentation, serologic testing, non-invasive imaging, and biopsy with histopathology testing [2,4].…”

“…Progression of symptoms to other organs is not uncommon, so patients require close follow-up and monitoring to assess for noncardiac involvement, including ophthalmologic, neurologic, and gastrointestinal screening [1]. Once a diagnosis of ATTR amyloidosis is suspected, biomarkers such as natriuretic peptides and high-sensitivity plasma troponin T (hsTnT) levels play a useful role as clinical indicators for disease progression and as predictors for survival [2]. In fact, studies have shown that cutoffs of 3000 pg/mL and 0.05 ng/mL for NT-proBNP and hsTnT, respectively, help stratify mortality risk in ATTR amyloidosis patients [9].…”

“…Over 30 different protein types have been identified as amyloidogenic, but the two most frequently implicated in cardiac amyloidosis are transthyretin (ATTR) and light chain (AL) amyloid [1]. Research suggests that the prevalence of ATTR is about 50,000 patients worldwide, with 80% of the affected population having cardiac involvement [2]. Presently, amyloidosis is underdiagnosed and underestimated as the cause for heart failure, conduction anomalies, and arrythmias.…”

Red flags to diagnose infiltrative cardiomyopathies

“…NT-proBNP и тропонины повышаются у пациентов с ИЗС вследствие инфильтративного процесса в миокарде или прямого токсического воздействия аномальных веществ на кардиомиоциты. В одном исследовании среди пациентов с AL-амилоидозом сердца уровень NT-proBNP никогда не был ниже 97,5 процентиля для нормальных людей, что указывает на 100% чувствительность; более того пороговое значение NT-proBNP 1285 нг/л имело точность 92% для выявления поражения сердца [26]. NT-рrоBNP может служить ранним индикатором диастолической дисфункции ЛЖ у пациентов с перегрузкой железом, БФ [15,23].…”