RESUMO
Abnormalities in impulse generation and transmission are among the first signs of cardiac remodeling in cardiomyopathies. Accordingly, 12-lead electrocardiogram (ECG) of patients with cardiomyopathies may show multiple abnormalities. Some findings are suggestive of specific disorders, such as the discrepancy between QRS voltages and left ventricular (LV) mass for cardiac amyloidosis or the inverted T waves in the right precordial leads for arrhythmogenic cardiomyopathy. Other findings are less sensitive and/or specific, but may orient toward a specific diagnosis in a patient with a specific phenotype, such as an increased LV wall thickness or a dilated LV. A "cardiomyopathy-oriented" mindset to ECG reading is important to detect the possible signs of an underlying cardiomyopathy and to interpret correctly the meaning of these alterations, which differs in patients with cardiomyopathies or other conditions.
Assuntos
Cardiomiopatias , Humanos , Cardiomiopatias/complicações , Cardiomiopatias/diagnóstico , Eletrocardiografia , Ventrículos do Coração , FenótipoRESUMO
Dilated cardiomyopathy (DCM) is a primitive heart muscle disease characterized by a great heterogeneous aetiology and prognostic outcome. Dilated cardiomyopathy is an umbrella term encompassing different aetiologies that might require specific treatments. It principally affects young and male adults, with high-risk arrhythmic competitive risk. Unfortunately, the prevention of major ventricular arrhythmic events remains a clinical challenge. In the era of advanced multimodality imaging and widely available genetic testing, electrocardiogram (ECG) continues to represent a reliable diagnostic tool, for specific work up of every single patient. However, approaching DCM patients, only a cardiomyopathy-oriented reading makes the role of ECG central in the management of DCM, both for diagnosis, prognosis, and therapeutic management. In this paper, we present four ECGs of four different DCM patients, in order to guide a cardiomyopathy-oriented ECG reading, emphasizing its impact in an early, cost-effective, and personalized diagnostic and prognostic work up in this specific setting.
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Amyloid cardiomyopathy is a condition characterized by intra-myocardial deposit of protein-like material, in fibrillar shape (amyloid), which presence determine a progressive thickening and stiffening of the cardiac walls leading to a cardiac dysfunction. The proteins most often involved with cardiac amyloid are the light chains of the immunoglobulin, typical of amyloidosis AL, and transthyretin, responsible for transthyretin amyloidosis, in both its forms, hereditary and wild type. An accurate estimate of the incidence of cardiac amyloidosis is still difficult due to the variety and complexity of the clinical presentation of the condition. Nonetheless, the condition has stimulated the interest of the scientific community, so that a specific diagnostic path has been developed, beginning from the clinical suspicion and first-line testing, such as electrocardiogram, echocardiogram, and blood work, to progress to the diagnostic confirmation using more sophisticated testing such as magnetic resonance, scintiscan, and eventually cardiac biopsy. To understand and recognize this condition is very important, stemming from the availability of 'aetiology oriented therapies' (designed to prevent, control and possibly regress amyloid deposition), which should be added to the 'supportive therapies', used for the treatment of the complication of the condition, namely heart failure.
RESUMO
In this issue of JNC, BW Spery and Coll report a retrospective analysis of 57 patients with transthyretin-related amyloidosis (ATTR) in an advanced phase of the disease who underwent 99mTechnetium-pyrophosphate (99mTcPYP) scintigraphy. Although relatively small and "negative," the study is relevant since it broadens our knowledge on the uptake of "bone tracers" in ATTR and contributes to understand the limitations of the clinical use of scintigraphy in this disease. The paper raises, directly or indirectly, at least three questions: To what extent are the different bone tracers interchangeable for the diagnosis of ATTR cardiac amyloidosis? Are bone tracers able to image non-cardiac ATTR amyloidosis? What is the explanation for the variable performance of the different bone tracers in the diagnosis of cardiac and extracardiac ATTR amyloidosis?
Assuntos
Pré-Albumina , Tecnécio , Difosfatos , Humanos , Cintilografia , Estudos RetrospectivosRESUMO
AIMS: Wild-type transthyretin amyloidosis (ATTRwt) is mostly considered a disease predominantly of elderly male, characterized by concentric LV hypertrophy, preserved LVEF, and low QRS voltages. We sought to describe the characteristics of a large cohort of ATTRwt patients to better define the disease. METHODS AND RESULTS: Clinical findings of consecutive ATTRwt patients diagnosed at 2 centres were reviewed. ATTRwt was diagnosed histologically or non-invasively (LV hypertrophy ≥12 mm, intense cardiac uptake at 99mTc-DPD scintigraphy and AL exclusion). Mutations in TTR were excluded in all cases. The study cohort comprised 108 patients (78.6 ± 8 years); 67 (62%) diagnosed invasively and 41 (38%) non-invasively. Twenty patients (19%) were females. An asymmetric hypertrophy pattern was observed in 25 (23%) patients. Mean LVEF was 52 ± 14%, with 39 patients (37%) showing a LVEF < 50%. Atrial fibrillation (56%) and a pseudo-infarct pattern (63%) were the commonest ECG findings. Only 22 patients fulfilled QRS low-voltage criteria while 10 showed LV hypertrophy on ECG. Although heart failure was the most frequent profile leading to diagnosis (68%), 7% of individuals presented with atrioventricular block and 11% were diagnosed incidentally. Almost one third (35; 32%) were previously misdiagnosed. CONCLUSION: The clinical spectrum of ATTRwt is heterogeneous and differs from the classic phenotype: women are affected in a significant proportion; asymmetric LV hypertrophy and impaired LVEF are not rare and only a minority have low QRS voltages. Clinicians should be aware of the broad clinical spectrum of ATTRwt to correctly identify an entity for which a number of disease-modifying treatments are under investigation.
Assuntos
Neuropatias Amiloides Familiares/patologia , Cardiomiopatias/diagnóstico , Idoso , Neuropatias Amiloides Familiares/diagnóstico por imagem , Cardiomiopatias/mortalidade , Cardiomiopatias/fisiopatologia , Erros de Diagnóstico , Difosfonatos , Ecocardiografia , Eletrocardiografia , Feminino , Técnicas de Genotipagem , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico , Hipertrofia Ventricular Esquerda/mortalidade , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Imagem Multimodal , Compostos de Organotecnécio , Estudos Prospectivos , Compostos Radiofarmacêuticos , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/métodosRESUMO
Cardiac amyloidosis (CA) leads to variable degrees of myocardial infiltration with a final echocardiographic phenotype of "hypertrophy." Although many non-invasive imaging techniques (MRI, CT, scintigraphy, PET) are useful, the definitive diagnosis is still based on myocardial histology. We explored the possible role of [18F]-NaF PET/CT in the diagnosis of this disease in two cases with wild-type (ATTRwt) or mutant (ATTRm) Ile68Leu transthyretin (TTR)-related CA.
Assuntos
Amiloidose/diagnóstico por imagem , Amiloidose/metabolismo , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Amiloidose/etiologia , Cardiomiopatias/etiologia , Diagnóstico Diferencial , Humanos , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/farmacocinética , Distribuição TecidualRESUMO
BACKGROUND: Immunoglobulin amyloid light-chain (AL)-related cardiac amyloidosis (CA) has a worse prognosis than either wild-type (ATTRwt) or mutant (ATTRm) transthyretin (TTR) CA. Detailed echocardiographic studies have been performed in AL amyloidosis but not in TTR amyloidosis and might give insight into this difference. We assessed cardiac structure and function and outcome in a large population of patients with CA and compared findings in TTR and AL-related disease. METHODS AND RESULTS: We analyzed 172 patients with CA (AL amyloidosis, n=80; ATTRm, n=36; ATTRwt, n=56) by standard echocardiography and 2-dimensional speckle-tracking imaging-derived left ventricular (LV) longitudinal (LS), radial, and circumferential strains. Despite a preserved LV ejection fraction (55±12%), LS was severely impaired in CA. Standard measures of LV function and speckle-tracking imaging worsened as wall thickness increased, whereas apical LS was preserved regardless of the pathogenesis of CA and the degree of wall thickening. Compared with ATTRm and AL amyloidosis, ATTRwt was characterized by greater LV wall thickness and lower ejection fraction. LS was more depressed in both ATTRwt and AL amyloidosis (-11±3% and -12±4%, respectively, P=0.54) than in ATTRm (-15±4%, P<0.01 versus AL amyloidosis and ATTRwt). TTR-related causes were favorable predictors of survival, whereas LS and advanced New York Heart Association class were negative predictors. CONCLUSIONS: In patients with CA, worsening LV function correlated with increasing wall thickness regardless of pathogenesis. Patients with ATTRwt had a statistically greater wall thickness but lesser mortality than those with AL amyloidosis, despite very similar degrees of LS impairment. This paradox suggests an additional mechanism for LV dysfunction in AL amyloidosis, such as previously demonstrated light-chain toxicity.
Assuntos
Neuropatias Amiloides Familiares/mortalidade , Amiloidose/mortalidade , Cardiomiopatias/mortalidade , Cadeias Leves de Imunoglobulina/metabolismo , Pré-Albumina/metabolismo , Função Ventricular Esquerda/fisiologia , Idoso , Idoso de 80 Anos ou mais , Neuropatias Amiloides Familiares/metabolismo , Neuropatias Amiloides Familiares/patologia , Amiloidose/metabolismo , Amiloidose/patologia , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/metabolismo , Diástole/fisiologia , Ecocardiografia , Feminino , Seguimentos , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , Prognóstico , Sístole/fisiologiaRESUMO
Cardiac amyloidosis (CA) is often misdiagnosed because of both physician-related and disease-related reasons including: fragmented knowledge among different specialties and subspecialties, shortage of centres and specialists dedicated to disease management, erroneous belief it is an incurable disease, rarity of the condition, intrinsic phenotypic heterogeneity, genotypic heterogeneity in transthyretin-related forms and the necessity of target organ tissue histological diagnosis in the vast majority of cases. Pitfalls, incorrect beliefs and deceits challenge not only the path to the diagnosis of CA but also the precise identification of aetiological subtype. The awareness of this condition is the most important prerequisite for the management of the risk of underdiagnoses and misdiagnosis. Almost all clinical, imaging and laboratory tests can be misinterpreted, but fortunately each of these diagnostic steps can also offer diagnostic "red flags" (i.e. highly suggestive findings that can foster the correct diagnostic suspicion and facilitate early, timely diagnosis). This is especially important because outcomes in CA are largely driven by the severity of cardiac dysfunction and emerging therapies are aimed at preventing further amyloid deposition.
Assuntos
Neuropatias Amiloides Familiares/diagnóstico , Cardiomiopatias/diagnóstico , Erros de Diagnóstico , Neuropatias Amiloides Familiares/genética , Cardiomiopatias/genética , Ecocardiografia , Eletrocardiografia , Genótipo , Humanos , Imageamento por Ressonância Magnética , Mutação , CintilografiaRESUMO
OBJECTIVES: Because patients with ATTRv cardiomyopathy are more likely to be male, this analysis aimed to increase information on associations between sex and genotype, phenotype, and degree of myocardial involvement in ATTRv amyloidosis. BACKGROUND: Transthyretin amyloid cardiomyopathy is a progressive, fatal disease that occurs due to accumulation of wild-type or variant (ATTRv) transthyretin amyloid fibrils in the myocardium. METHODS: The Transthyretin Amyloidosis Outcomes Survey (THAOS) is an ongoing global longitudinal observational survey of patients with ATTR amyloidosis and asymptomatic carriers with TTR mutations. Data from THAOS (data cutoff: January 6, 2020) were analyzed to determine any sex-based differences in genotype, phenotype, and presence of cardiac and neurological symptoms in patients with ATTRv amyloidosis and in patients with ATTRv amyloidosis and cardiomyopathy. RESULTS: There were 2,790 patients with ATTRv amyloidosis enrolled in THAOS, with male patients more likely to have symptoms of cardiac involvement and a cardiac phenotype. Male prevalence was greater in patients with more severe cardiac manifestations of disease, as assessed with N-terminal pro-B-type natriuretic peptide, left-ventricular (LV) ejection fraction, mean LV wall thickness divided by height, and LV mass index divided by height. Sex, age at disease onset, and genotype category were identified by multivariate analyses as risk factors for the development of cardiomyopathy (defined as increased LV septum thickness divided by height). CONCLUSIONS: In this analysis, myocardial involvement was more frequent and pronounced in male patients with ATTRv amyloidosis, suggesting that there may be biological characteristics that inhibit myocardial amyloid infiltration in females or facilitate it in males.
Assuntos
Neuropatias Amiloides Familiares , Insuficiência Cardíaca , Neuropatias Amiloides Familiares/complicações , Neuropatias Amiloides Familiares/epidemiologia , Neuropatias Amiloides Familiares/genética , Feminino , Humanos , Masculino , Pré-Albumina/genética , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: The aim of this study was to assess the diagnostic accuracy of bone scintigraphy in a large multicenter cohort of patients with cardiac amyloidotic involvement and Phe64Leu transthyretin (TTR) mutation. BACKGROUND: Diagnostic accuracy of bone scintigraphy for transthyretin-related cardiac amyloidosis (TTR-CA) is considered extremely high, enabling this technique to be the noninvasive diagnostic standard for TTR-CA. Nevertheless, this approach has not been systematically validated across the entire spectrum of TTR mutations. METHODS: A total of 55 patients with Phe64Leu TTR mutation were retrospectively analyzed and evaluated between 1993 and 2018 at 7 specialized Italian tertiary centers. Cardiac involvement was defined as presence of an end-diastolic interventricular septum thickness ≥12 mm, without other possible causes of left ventricular hypertrophy (i.e., arterial hypertension or valvulopathies). A technetium-99m (99mTc)-diphosphonate (DPD) or 99mTc-hydroxyl-methylene-diphosphonate (HMDP) bone scintigraphy was reviewed, and visual scoring was evaluated according to Perugini's method. RESULTS: Among 26 patients with definite cardiac involvement, 19 underwent 99mTc-DPD or 99mTc-HMDP bone scintigraphy. Of them, 17 (89.5%) patients had low or absent myocardial bone tracer uptake, whereas only 2 (10.5%) showed high-grade myocardial uptake. The sensitivity and the accuracy of bone scintigraphy in detecting TTR-CA were 10.5% and 37%, respectively. Patients with cardiac involvement and low or absent bone tracer uptake were similar to those with high-grade myocardial uptake in terms of age, sex, and electrocardiographic and echocardiographic findings. CONCLUSIONS: The sensitivity of bone scintigraphy (DPD and HMDP) in detecting TTR-CA is extremely low in patients with Phe64Leu TTR mutation, suggesting the need to assess diagnostic accuracy of bone scintigraphy to identify cardiac involvement across a wider spectrum of TTR mutations.
Assuntos
Neuropatias Amiloides Familiares/diagnóstico por imagem , Osso e Ossos/diagnóstico por imagem , Cardiomiopatias/diagnóstico por imagem , Difosfonatos/administração & dosagem , Mutação , Pré-Albumina/genética , Cintilografia , Compostos Radiofarmacêuticos/administração & dosagem , Compostos de Tecnécio/administração & dosagem , Medronato de Tecnécio Tc 99m/análogos & derivados , Imagem Corporal Total , Idoso , Neuropatias Amiloides Familiares/genética , Cardiomiopatias/genética , Feminino , Predisposição Genética para Doença , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medronato de Tecnécio Tc 99m/administração & dosagemRESUMO
AIMS: We aimed to assess carpal tunnel syndrome (CTS) prevalence in transthyretin (TTR)-related and light-chain amyloidosis (AL), comparing it to the general population, adjusted for age and gender. In TTR-related amyloidosis (ATTR) we investigated (i) CTS prevalence in relation to genotype, cardiac amyloidosis (CA), age and gender; (ii) CTS role as an incremental risk factor for CA; (iii) temporal relationship between CTS and CA; and (iv) CTS prognostic role. METHODS AND RESULTS: Data from 538 subjects (166 hereditary ATTR, 107 wild-type ATTR, 196 AL amyloidosis, and 69 TTR mutation carriers; 64% male, median age 62.4 years), evaluated at our centre (Bologna, Italy), were analysed and compared to a published cohort of 14.9 million people, in which incidence rates of CTS had been estimated. CTS prevalence was highest in ATTR patients with CA (20.3% vs. 4.1% in the general population), while it was comparable to the general population when CA was absent and in AL patients. CTS standardized incidence rates were markedly elevated in ATTR males in the eighth decade of life (13.08 in hereditary ATTR, 15.5 in wild-type ATTR). The risk of developing CA was greater in ATTR patients with CTS; the probability of having CTS was highest 5-9 years prior to CA diagnosis. CTS was an independent mortality risk factor in ATTR. CONCLUSIONS: Compared to general population the adjusted prevalence of CTS is higher among elderly men with ATTR; CTS is a prognostic marker in ATTR, independently of cardiac involvement, and precedes CA diagnosis by 5-9 years. The awareness of this association and time delay offers the possibility of an early pre-clinical ATTR-CA diagnosis.
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Amiloidose , Síndrome do Túnel Carpal , Insuficiência Cardíaca , Síndrome do Túnel Carpal/diagnóstico , Síndrome do Túnel Carpal/epidemiologia , Síndrome do Túnel Carpal/etiologia , Diagnóstico Precoce , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
AIMS: Cardiac amyloidosis remains a great challenge for the cardiologist. One of the three main aetiological forms, transthyretin-related hereditary amyloidosis (ATTRm), can present with several phenotypes, depending mainly on the specific mutation. We aimed to characterize the phenotype of patients with ATTRm due to Ile68Leu mutation, comparing them to patients with wild-type transthyretin amyloidosis (ATTRwt). METHODS AND RESULTS: Data of 67 Ile68Leu ATTRm patients from two Italian referral centres (Bologna and Florence) were retrospectively analysed and compared to those of 82 ATTRwt patients. Fifty-five unaffected mutation carriers were also analysed. Cumulative disease onset was 50% at age 71. A total of 56/67 (84%) patients had a predominantly cardiac phenotype at presentation with concentric increase in left ventricular wall thickness [median 17 mm], and normal or near normal left ventricular ejection fraction (79% of patients). Low QRS voltages were present only in 29% of patients but voltage/mass ratio was low (0.5). Carpal tunnel syndrome was noted in 43%. The overall phenotypic profile was similar to ATTRwt but Ile68Leu ATTRm patients typically presented younger (median 71 vs. 78 years) and were more likely to have (mild) symptomatic neurological involvement (19% vs. 2%). Male prevalence was 44% in unaffected mutation carriers and 78% in affected patients. Age-adjusted survival was comparable between groups. CONCLUSIONS: Ile68Leu ATTRm is a cause of familial amyloidotic cardiomyopathy endemic in central-northern Italy and presents as hypertrophic/restrictive cardiomyopathy quite similar to ATTRwt. Male preponderance is present in affected patients but not in unaffected mutation carriers. Age-adjusted survival is similar to ATTRwt.
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Neuropatias Amiloides Familiares/genética , Cardiomiopatias/genética , Insuficiência Cardíaca/etiologia , Ventrículos do Coração/fisiopatologia , Função Ventricular Esquerda/fisiologia , Idoso , Idoso de 80 Anos ou mais , Neuropatias Amiloides Familiares/complicações , Neuropatias Amiloides Familiares/epidemiologia , Cardiomiopatias/complicações , Cardiomiopatias/diagnóstico , Análise Mutacional de DNA , Ecocardiografia , Eletrocardiografia , Feminino , Seguimentos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Ventrículos do Coração/diagnóstico por imagem , Humanos , Incidência , Itália/epidemiologia , Masculino , Mutação , Fenótipo , Estudos Retrospectivos , Taxa de Sobrevida/tendênciasRESUMO
Tc-DPD (Tc-3,3-diphosphono-1,2-propanodicarboxylic acid) has a high affinity for transthyretin (TTR)-infiltrated myocardium, allowing a differential diagnosis with light chain cardiac amyloidosis and other nonamyloidotic cardiomyopathies with a hypertrophic phenotype, in which myocardial tracer uptake is low or absent. Myocardial bone tracer uptake in the rarer forms of amyloidosis (eg, apolipoprotein-related) has been rarely studied. We present 4 cases of cardiac amyloidosis that underwent Tc-DPD scintigraphy; myocardial DPD uptake was present in patients with ATTR, wtTTR and apolipoprotein AI and negative in cases with AL and apolipoprotein AII-related disease.
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Amiloidose/diagnóstico por imagem , Cardiomiopatias/diagnóstico por imagem , Difosfonatos , Compostos de Organotecnécio , Compostos Radiofarmacêuticos , Amiloidose/etiologia , Cardiomiopatias/etiologia , Humanos , CintilografiaRESUMO
BACKGROUND: Although atrial fibrillation (AF) is a known complication of amyloidotic cardiomyopathy (AC), a precise pathophysiological and prognostic characterization is not available. We therefore aimed to assess prevalence, incidence, risk factors and prognostic significance of AF in light-chain (AL), hereditary transthyretin-related (m-ATTR) and non-mutant transthyretin-related (wt-ATTR) AC. METHODS: Retrospective study of 262 patients with AC (123 AL, 94 m-ATTR, 45 wt-ATTR) from a single center. RESULTS: AF prevalence was 15% (AL 9%, m-ATTR 11%, wt-ATTR 40%). During a median follow-up of 1.2 years 11 patients developed AF (2.1% person-years). Age, heart failure (HF), left ventricular (LV) ejection fraction, renal involvement, left atrial size and right atrial pressure were independently associated with AF. AF was associated with incident HF but not with increased mortality. All AF patients were prescribed warfarin and none suffered thromboembolic events. CONCLUSIONS: In AC the prevalence of AF varies widely according to etiology with a mean value of 15% that reaches 40% in wt-ATTR amyloidosis. Age, HF, LV ejection fraction, left atrial size and right atrial pressure were the main independent risk factors, while wall thickness and etiology were not the main independent risk factors. AF does not seem to impact all-cause mortality but was strongly associated with prevalent and incident HF.
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Amiloidose/diagnóstico , Fibrilação Atrial/diagnóstico , Cardiomiopatias/diagnóstico , Insuficiência Cardíaca/diagnóstico , Tromboembolia/diagnóstico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Amiloidose/sangue , Amiloidose/complicações , Amiloidose/mortalidade , Anticoagulantes/uso terapêutico , Fibrilação Atrial/sangue , Fibrilação Atrial/complicações , Fibrilação Atrial/mortalidade , Cardiomiopatias/sangue , Cardiomiopatias/complicações , Cardiomiopatias/mortalidade , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/mortalidade , Humanos , Incidência , Itália/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Pré-Albumina/metabolismo , Prevalência , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Volume Sistólico , Análise de Sobrevida , Tromboembolia/sangue , Tromboembolia/etiologia , Tromboembolia/prevenção & controle , Função Ventricular Esquerda , Varfarina/uso terapêuticoRESUMO
Transthyretin (TTR)-related amyloidosis is a disease caused by the deposition of insoluble fibrils deriving from the misfolding of TTR, a protein mainly produced by the liver. In the hereditary form of the disease (ATTRm), protein misfolding is secondary to a mutation in the TTR gene. ATTRm can manifest with different phenotypes: mainly neurological, mainly cardiac, or mixed. In the senile form of the disease (wild-type TTR or SSA), the deposition of non-mutated TTR occurs and, clinically, cardiomyopathy is predominant. Cardiac amyloidosis is still an underdiagnosed disease and clinical heterogeneity makes the diagnosis challenging. Until recently, no specific pharmacological treatment was available, liver transplantation being the only therapeutic option aimed at slowing disease progression in ATTRm and treatment was based on symptom relief. This review focuses on the emerging pharmacological treatments for TTR-related amyloidosis targeting different steps of the amyloidogenic process (blocking hepatic TTR synthesis, TTR tetramer stabilization and promotion of TTR amyloid fibril clearance).