RESUMEN
Cardiac amyloidosis (CA) is caused by the myocardial deposition of misfolded proteins, either amyloid transthyretin (ATTR) or immunoglobulin light chains (AL). The paradigm of this condition has transformed, since CA is increasingly recognized as a relatively prevalent cause of heart failure. Cardiac scintigraphy with bone tracers is the unique noninvasive technique able to confirm CA without performing tissue biopsy or advanced imaging tests. A moderate-to-intense myocardial uptake (Perugini grade ≥2) associated with the absence of a monoclonal component is greater than 99% specific for ATTR-CA, while AL-CA confirmation requires tissue biopsy.
Asunto(s)
Amiloidosis , Cardiomiopatías , Radiofármacos , Humanos , Cardiomiopatías/diagnóstico por imagen , Cardiomiopatías/metabolismo , Amiloidosis/diagnóstico por imagen , Amiloidosis/metabolismo , Amiloidosis/patología , Cintigrafía/métodos , Huesos/diagnóstico por imagen , Huesos/metabolismo , Huesos/patología , Miocardio/patología , Miocardio/metabolismo , Neuropatías Amiloides Familiares/diagnóstico por imagen , Neuropatías Amiloides Familiares/metabolismo , Neuropatías Amiloides Familiares/patología , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/metabolismo , Prealbúmina/metabolismoRESUMEN
Amyloidosis refers to a heterogeneous group of disorders sharing common pathophysiological mechanisms characterized by the extracellular accumulation of fibrillar deposits consisting of the aggregation of misfolded proteins. Cardiac amyloidosis (CA), usually caused by deposition of misfolded transthyretin or immunoglobulin light chains, is an increasingly recognized cause of heart failure burdened by a poor prognosis. CA manifests with a restrictive cardiomyopathy which progressively leads to biventricular thickening, diastolic and then systolic dysfunction, arrhythmias, and valvular disease. The pathophysiology of CA is multifactorial and includes increased oxidative stress, mitochondrial damage, apoptosis, impaired metabolism, and modifications of intracellular calcium balance.
Asunto(s)
Amiloidosis , Cardiomiopatías , Humanos , Amiloidosis/fisiopatología , Amiloidosis/metabolismo , Cardiomiopatías/fisiopatología , Cardiomiopatías/metabolismo , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/metabolismo , Estrés Oxidativo , Miocardio/patología , Miocardio/metabolismoRESUMEN
BACKGROUND: Patients with cardiac amyloidosis (CA) often experience heart failure (HF) episodes. No evidence is available on inotropic therapy. This study aims to fill this gap by examining the safety and efficacy of levosimendan. METHODS: We retrieved all HF patients receiving ≥1 levosimendan infusion from 2013 to 2023. CA patients were matched with HF patients without CA (controls) based on sex, age, and left ventricular ejection fraction (LVEF). The response to levosimendan was measured as changes in daily urinary output, body weight, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and estimated glomerular filtration rate (eGFR). RESULTS: CA patients (median age 77 years, 73% men, 59% with ATTR-CA) and controls were compared. Levosimendan infusion was stopped because of hypotension in 2 cases with CA and (in 1 case) worsening renal function, and in 2 controls because of ventricular tachycardia episodes and (in 1 case) hypotension. CA patients showed a trend toward increased daily urinary output (p = 0.078) and a significant decrease in body weight (p < 0.001), without significant changes in NT-proBNP (p = 0.497) and eGFR (p = 0.732). Both CA patients and controls displayed similar changes in urinary output, weight, and eGFR, but NT-proBNP decreased more significantly among controls (p < 0.001). No differences were noted in rehospitalization rates, but CA patients experienced higher mortality at 6 and 12 months (p = 0.003 and p = 0.001, respectively). CONCLUSIONS: Levosimendan appears safe for CA patients needing inotropic support. The diuretic response and weight decrease during hospitalization were comparable between CA patients and matched HF patients, despite the greater mortality of CA patients after discharge.
Asunto(s)
Amiloidosis , Cardiomiopatías , Cardiotónicos , Simendán , Humanos , Simendán/uso terapéutico , Simendán/administración & dosificación , Masculino , Femenino , Anciano , Amiloidosis/tratamiento farmacológico , Amiloidosis/complicaciones , Amiloidosis/mortalidad , Resultado del Tratamiento , Anciano de 80 o más Años , Cardiotónicos/uso terapéutico , Cardiotónicos/efectos adversos , Cardiotónicos/administración & dosificación , Cardiomiopatías/tratamiento farmacológico , Estudios Retrospectivos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/mortalidad , Persona de Mediana EdadRESUMEN
Over the last years, there has been a growing interest in the clinical manifestations and outcomes of cardiomyopathies in women. Peripartum cardiomyopathy is the only women-specific cardiomyopathy. In cardiomyopathies with X-linked transmission, women are not simply healthy carriers of the disorder, but can show a wide spectrum of clinical manifestations ranging from mild to severe manifestations because of heterogeneous patterns of X-chromosome inactivation. In mitochondrial disorders with a matrilinear transmission, cardiomyopathy is part of a systemic disorder affecting both men and women. Even some inherited cardiomyopathies with autosomal transmission display phenotypic and prognostic differences between men and women. Notably, female hormones seem to exert a protective role in hypertrophic cardiomyopathy (HCM) and variant transthyretin amyloidosis until the menopausal period. Women with cardiomyopathies holding high-risk features should be referred to a third-level center and evaluated on an individual basis. Cardiomyopathies can have a detrimental impact on pregnancy and childbirth because of the associated hemodynamic derangements. Genetic counselling and a tailored cardiological evaluation are essential to evaluate the likelihood of transmitting the disease to the children and the possibility of a prenatal or early post-natal diagnosis, as well as to estimate the risk associated with pregnancy and delivery, and the optimal management strategies.
Asunto(s)
Cardiomiopatías , Humanos , Femenino , Cardiomiopatías/terapia , Cardiomiopatías/diagnóstico , Cardiomiopatías/fisiopatología , Cardiomiopatías/genética , Embarazo , Complicaciones Cardiovasculares del Embarazo/terapia , Complicaciones Cardiovasculares del Embarazo/fisiopatología , Complicaciones Cardiovasculares del Embarazo/diagnóstico , Complicaciones Cardiovasculares del Embarazo/genética , Cardiomiopatía Hipertrófica/terapia , Cardiomiopatía Hipertrófica/genética , Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/fisiopatología , Asesoramiento Genético/métodos , Manejo de la EnfermedadRESUMEN
BACKGROUND: An app providing material for education and entertaining is a possible way to support patients and healthcare providers in achieving person-centered care. METHODS: An app tailored on the Fondazione Toscana Gabriele Monasterio (FTGM), a research hospital treating cardiac and lung disorders, was created. A pilot evaluation project was conducted on consecutive patients hospitalized for heart or lung disorders. Patients were asked to complete an assessment questionnaire. RESULTS: The FTGM app provides information on diagnostic and therapeutic investigations, hospital and healthcare personnel, and includes content for entertainment and learning. It was tested on 215 consecutive patients (75% men, 66% aged >60âyears, and 40% with a primary or middle school degree). Sixty-nine percentage of patients used the FTGM app, including 67% of patients aged >80âyears and 65% of those with an elementary education (65%). Patients gave positive feedback on the app layout. Many (76%) looked for information on doctors and nurses in the 'People' section. Sixty-five percent of responders had used at least one of the sections called 'Music' and 'Museum visits'. The app helped many patients perceive the hospital as a more liveable place (68%), and to feel less anxious (76%), and more engaged in the diagnostic and therapeutic workup (65%). Overall, the majority of responders (87%) rated the app as 'excellent' or 'good', and almost all (95%) would have recommended other patients to use the app. CONCLUSIONS: The FTGM app is a possible tool to improve patient wellbeing during hospitalization.
Asunto(s)
Enfermedades Pulmonares , Aplicaciones Móviles , Femenino , Humanos , Masculino , Salud Digital , Pacientes Internos , Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/terapia , Persona de Mediana Edad , Anciano , Anciano de 80 o más AñosRESUMEN
BACKGROUND: We aimed to evaluate the physical and mental well being of people working in our academic institution. METHODS: This online survey targeted professors ( n â=â108), researchers ( n â=â78), technical and administrative staff ( n â=â279) working in the Scuola Superiore Sant'Anna (Pisa, Italy). Twenty-four multiple-choice questions explored the physical and mental health status, the main cardiovascular risk factors and levels of physical activity, the risk of cancer, and eating and drinking habits. RESULTS: Over 1âweek, 112 participants out of 465 (24%) completed the survey [69% women, median age 43âyears (interquartile range 33-53)]. The physical and mental health were judged as 'poor' by 5% and 13%. Many individuals had at least one cardiovascular risk factor (diabetes, 4%; hypertension, 10%; family history of coronary artery disease before 40âyears, 21%; hypercholesterolemia, 24%; current or former smoking habit, 39%), and 6% had all of them. Many participants were rather sedentary: for example, 44% never or hardly ever walked at a quick pace for ≥20 min. As for eating and drinking habits, 36% ate sweets five or six times a week or every day, 15% drank beer and/or wine at least five or six times a week, and 5% drank spirits three or four times a week. CONCLUSIONS: A small but not negligeable proportion of responders complained of 'poor' health, and 65% had at least one cardiovascular risk factor. The global levels of physical activity and eating and drinking habits were globally suboptimal. Educational and screening activities to improve the wellbeing of people working in academia are advisable.
Asunto(s)
Consumo de Bebidas Alcohólicas , Vino , Humanos , Femenino , Adulto , Masculino , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/epidemiología , Universidades , Cerveza , Estado de SaludRESUMEN
OBJECTIVE: To investigate end-of-life (EoL) care for heart failure (HF) in Tuscany (Italy) from healthcare professionals' perspective and identify areas for intervention. METHODS: All the directors of Cardiology units (n = 29) and palliative care (PC) units (n = 14) in Tuscany were surveyed on the practices of EoL care. RESULTS: Forty-five percent of cardiologists reported that their hospital had some EoL care services for HF patients. However, 75% did not have a multidisciplinary team providing EoL care for HF patients. Sixty-four percent stated that <25% of patients who might benefit from PC did receive it, and 18% stated that no patient received PC. For most of PC specialists, HF patients accounted for <25% of their patients. PC specialists believed that patients with cancer diseases were much more likely to receive PC than HF patients at EoL, and 36% judged that almost no HF patients were timely referred to hospice care. The majority of PC specialists reported that almost no HF patient prepared advance healthcare directives, as opposite to 57% for cancer patients, suggesting poor understanding or acceptance of their terminal condition. CONCLUSIONS: The management of HF patients in the EoL stage in Tuscany is often suboptimal. EoL care should be implemented to ensure an adequate quality of life to these patients.
Asunto(s)
Insuficiencia Cardíaca , Cuidados Paliativos al Final de la Vida , Neoplasias , Cuidado Terminal , Humanos , Calidad de Vida , Cuidados Paliativos , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/terapiaRESUMEN
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.
Asunto(s)
Cardiomiopatías , Humanos , Cardiomiopatías/complicaciones , Cardiomiopatías/diagnóstico , Electrocardiografía , Ventrículos Cardíacos , FenotipoRESUMEN
Cardiac amyloidosis (CA) is an underdiagnosed condition caused by the deposition of misfolded proteins, namely immunoglobulin light chains and transthyretin, in the extracellular spaces of the heart. Any cardiovascular structure can be affected by amyloid infiltration, including the valves. Amyloid accumulation within the cardiac valves may lead to their structural and functional impairment, with a profound impact on patients' prognosis and quality of life. The most common forms of valvular disease in CA are aortic stenosis (AS), mitral regurgitation (MR), and tricuspid regurgitation (TR). CA and AS share similar risk factors, disease mechanisms, and remodeling patterns, which make their diagnosis particularly challenging. Patients with both CA and AS experience worse outcomes than CA or AS alone, and transcatheter aortic valve replacement may represent a useful therapeutic strategy in this population. Data on MR and TR are quite limited and mainly coming from case reports or small series. This review paper will summarize our current understanding on the epidemiology, disease mechanisms, echocardiographic features, clinical implications, and therapeutic options of AS, MR, and TR in patients with CA.
Asunto(s)
Amiloidosis , Estenosis de la Válvula Aórtica , Enfermedades de las Válvulas Cardíacas , Insuficiencia de la Válvula Mitral , Insuficiencia de la Válvula Tricúspide , Humanos , Calidad de Vida , Enfermedades de las Válvulas Cardíacas/complicaciones , Enfermedades de las Válvulas Cardíacas/epidemiología , Enfermedades de las Válvulas Cardíacas/cirugía , Insuficiencia de la Válvula Mitral/cirugía , Insuficiencia de la Válvula Tricúspide/etiología , Insuficiencia de la Válvula Tricúspide/cirugía , Estenosis de la Válvula Aórtica/complicaciones , Estenosis de la Válvula Aórtica/cirugía , Amiloidosis/complicacionesRESUMEN
Obstructive sleep apneas (OSA) are a breathing disorder characterized by recurrent apneas and hypopneas associated with complete or partial obstruction of the upper airways during sleep, resulting in disturbed sleep architecture, repeated hypoxemia and awakenings, and daytime sleepiness. OSA syndrome affects up to 34% of men and 17% of women in Western countries. Abnormalities in upper airway anatomy (frequently due to obesity), muscle tone, or neural control of breathing are the main causes. OSA is associated with impaired cognitive function and favors the onset of hypertension, being a major determinant of resistant hypertension, and may favor cardiovascular diseases (e.g., coronary artery disease and heart failure), thereby increasing mortality. Polysomnography and (cardio)-respiratory portable systems are used to diagnose and determine the severity of OSA. Management of OSA includes lifestyle modifications, such as weight loss and avoidance of supine sleep position, and continuous positive airway pressure. Mandibular advancement devices and upper airway surgery may also be appropriate for some patients. Hypoglossal nerve stimulation and pharmacological interventions are currently investigated to improve symptoms and outcomes.
Asunto(s)
Enfermedades Cardiovasculares , Enfermedad de la Arteria Coronaria , Hipertensión , Apnea Obstructiva del Sueño , Masculino , Humanos , Femenino , Enfermedades Cardiovasculares/complicaciones , Factores de Riesgo , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/terapia , Enfermedad de la Arteria Coronaria/complicaciones , Hipertensión/complicaciones , Presión de las Vías Aéreas Positiva Contínua/efectos adversosRESUMEN
BACKGROUND: The anti-inflammatory drug colchicine improves the outcome of patients with myocardial infarction (MI). As an intense inflammatory and fibrotic response after MI may lead to scar expansion and left ventricular (LV) remodeling, the clinical benefit of colchicine could be related to a positive effect on the infarct scar and LV remodeling. METHODS: Pigs underwent left anterior descending artery occlusion through an angioplasty balloon for 90âmin and were then randomized into two groups: standard therapy [ACE inhibitor, beta blocker, mineralocorticoid receptor antagonist (MRA), aspirin] plus colchicine (nâ=â14) or standard therapy alone (nâ=â13). The pigs were treated for 30âdays and underwent two cardiac magnetic resonance (CMR) scans at 72âh and 30âdays. The pigs were then sacrificed the day after the second CMR. The primary efficacy end point was the extent of fibrosis in the infarct zone (calculated on eight samples from this zone and averaged). RESULTS: In the hearts explanted after 31âdays, pigs in the colchicine group had less fibrosis in the infarct zone than the other animals [41.6% (20.4-51.0) vs. 57.4% (42.9-66.5); Pâ=â0.022]. There was a trend toward a higher myocardial salvage index (MSI; an index of the efficacy of revascularization) in pigs on colchicine (Pâ=â0.054). Conversely, changes in LV volumes, ejection fraction and mass did not differ between groups. CONCLUSION: Colchicine therapy for 1âmonth after reperfused MI further reduces myocardial fibrosis when added to standard therapy, while it does not have additional effects on LV remodeling.
Asunto(s)
Cicatriz , Infarto del Miocardio , Porcinos , Humanos , Animales , Cicatriz/patología , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/tratamiento farmacológico , Miocardio/patología , Imagen por Resonancia Magnética , Fibrosis , Remodelación VentricularRESUMEN
Randomized controlled trials showing a significant benefit are met with enthusiasm because they may change the standard of care for patients who share the clinical and pathophysiologic characteristics of trial participants. Nonetheless, a well-designed and fully executed trial with neutral or negative findings also represents a critically important investigation deserving careful scientific scrutiny. In this paper we propose a 10-step approach to the interpretation of neutral or negative trials to exclude important methodological issues before concluding that the treatment really does not work. We will discuss this approach using the most classic trials of the past and some notable examples among superiority trials (mostly phase 3 trials) published over the last years.
Asunto(s)
Sistema Cardiovascular , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Cardiac fibrosis is characterized by the deposition of extracellular matrix proteins in the spaces between cardiomyocytes following both acute and chronic tissue damage events, resulting in the remodeling and stiffening of heart tissue. Fibrosis plays an important role in the pathogenesis of many cardiovascular disorders, including heart failure and myocardial infarction. Several studies have identified fibroblasts, which are induced to differentiate into myofibroblasts in response to various types of damage, as one of the most important cell types involved in the fibrotic process. There are currently no drugs with primarily antifibrotic action approved for clinical use, as the evidence of a clinical efficacy of these drugs is extremely limited, despite the numerous encouraging results from experimental studies. A new approach is represented by the use of chimeric antigen receptor T cells engineered in vivo using lipid nanoparticles containing mRNA encoding a receptor directed against the fibroblast activation protein, expressed by activated cardiac fibroblasts. This strategy has proved to be safe and effective in reducing myocardial fibrosis and improving cardiac function in mouse models of cardiac fibrosis. Clinical studies are required to test this novel approach in humans.
Asunto(s)
Insuficiencia Cardíaca , Infarto del Miocardio , Humanos , Animales , Ratones , Insuficiencia Cardíaca/terapia , Modelos Animales de Enfermedad , Miocitos Cardíacos , Linfocitos TRESUMEN
Amyloid light-chain (AL) amyloidosis is a hematological disorder characterized by abnormal proliferation of a plasma cell clone producing monoclonal free light chains that misfold and aggregate into insoluble fibrils in various tissues. Cardiac involvement is a common feature leading to restrictive cardiomyopathy and poor prognosis. Current first-line treatments aim at achieving hematological response by targeting the plasma cell clones, and these have been adapted from multiple myeloma therapy. Patients with AL amyloidosis often exhibit multiorgan involvement, making them susceptible to cancer therapy-related cardiovascular toxicity. Managing AL amyloidosis is a complex issue that requires enhanced knowledge of the cardio-oncological implications of hematological treatments. Future research should focus on implementing and validating primary and secondary prevention strategies and understanding the biochemical basis of oncological therapy-related damage to mitigate cardiovascular toxicity.
RESUMEN
Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) is a progressive and increasingly recognized cause of heart failure which is associated with high mortality and morbidity. ATTR-CM is characterized by the misfolding of TTR monomers and their deposition within the myocardium as amyloid fibrils. The standard of care for ATTR-CM consists of TTR-stabilizing ligands, such as tafamidis, which aim at maintaining the native structure of TTR tetramers, thus preventing amyloid aggregation. However, their efficacy in advanced-staged disease and after long-term treatment is still a source of concern, suggesting the existence of other pathogenetic factors. Indeed, pre-formed fibrils present in the tissue can further accelerate amyloid aggregation in a self-propagating process known as "amyloid seeding". The inhibition of amyloidogenesis through TTR stabilizers combined with anti-seeding peptides may represent a novel strategy with additional benefits over current therapies. Finally, the role of stabilizing ligands needs to be reassessed in view of the promising results derived from trials which have evaluated alternative strategies, such as TTR silencers and immunological amyloid disruptors.
RESUMEN
Cardiac amyloidosis (CA) is an infiltrative disease caused by progressive deposition of amyloid fibres in the heart. The most common forms include immunoglobulin light-chain and transthyretin amyloidosis. Current therapies for CA either stabilize or block the production of amyloidogenic precursors, preventing further amyloid deposition. This approach, while reducing cell damage and disease progression, does not target pre-existing amyloid deposits. Conversely, amyloid removal might stimulate functional recovery of the affected organ, thus improving quality of life and survival. A therapeutic strategy based on monoclonal antibodies capable of selectively binding amyloid deposits and inducing their removal has recently been tested in various clinical trial, with promising results, and could represent a key treatment for CA in the near future.
RESUMEN
Cardiac fibrosis is characterized by the deposition of extracellular matrix proteins in the spaces between cardiomyocytes following both acute and chronic tissue damage events, resulting in the remodeling and stiffening of heart tissue. Fibrosis plays an important role in the pathogenesis of many cardiovascular disorders, including heart failure and myocardial infarction. Several studies have identified fibroblasts, which are induced to differentiate into myofibroblasts in response to various types of damage, as the most important cell types involved in the fibrotic process. Some drugs, such as inhibitors of the renin-angiotensin-aldosterone system, have been shown to be effective in reducing cardiac fibrosis. There are currently no drugs with primarily anti-fibrotic action approved for clinical use, as well as the evidence of a clinical efficacy of these drugs is extremely limited, despite the numerous encouraging results from experimental studies. A new approach is represented by the use of CAR-T cells engineered in vivo using lipid nanoparticles containing mRNA coding for a receptor directed against the FAP protein, expressed by cardiac myofibroblasts. This strategy has proved to be safe and effective in reducing myocardial fibrosis and improving cardiac function in mouse models of cardiac fibrosis. Clinical studies are required to test this novel approach in humans.
Asunto(s)
Infarto del Miocardio , Receptores Quiméricos de Antígenos , Ratones , Animales , Humanos , Receptores Quiméricos de Antígenos/metabolismo , Miocitos Cardíacos/metabolismo , Infarto del Miocardio/metabolismo , Fibroblastos/metabolismo , Fibrosis , Tratamiento Basado en Trasplante de Células y Tejidos , Miocardio/metabolismoRESUMEN
Heart failure (HF) is a significant cause of morbidity and mortality worldwide. HF with preserved ejection fraction (HFpEF) is a complex syndrome, often participated by several cardiac and extracardiac conditions, including chronic kidney disease, pulmonary disease, anaemia and advanced age. Circulating biomarkers reflecting pathophysiological pathways involved in HFpEF development and progression may assist clinicians in early diagnosis and management of this condition. Natriuretic peptides (NPs) are cardioprotective hormones released by cardiomyocytes in response to pressure or volume overload and in response to activation of neuro-endocrine-immune system. The relevance of B-type NP (BNP) and N-terminal pro-B-type NP (NT-proBNP) for diagnosis and risk stratification has been extensively demonstrated, and these biomarkers are emerging tools for population screening and as guides to the start of treatment in subclinical HF. On the contrary, conflicting evidence exists on the value of NPs to guide HF therapy. Among the other biomarkers, high-sensitivity troponins and soluble suppression of tumorigenesis-2 are the most promising biomarkers for risk stratification, predicting outcome independently from NPs. In this review, some novel biomarkers are being tested in such clinical scenario, more tightly linked to specific pathophysiological processes of cardiac damage.
RESUMEN
Transthyretin (TTR) is a tetrameric transport protein mainly synthesized by the liver and choroid plexus. ATTR amyloidosis is characterized by the misfolding of TTR monomers and their accumulation within tissues as amyloid fibres. Current therapeutic options rely on the blockade of TTR production, TTR stabilization to maintain the native structure of TTR, amyloid degradation, or induction of amyloid removal from tissues. "Amyloid seeds" are defined as small fibril fragments that induce amyloid precursors to assume a structure rich in ß-sheets, thus promoting fibrillogenesis. Amyloid seeds are important to promote the amplification and spread of amyloid deposits. Further studies are needed to better understand the molecular structure of ATTR seeds (i.e. the characteristics of the most amyloidogenic species), and the conditions that promote the formation and multiplication of seeds in vivo. The pathological cascade may begin months to years before symptom onset, suggesting that seeds in tissues might potentially be used as biomarkers for the early disease stages. Inhibition of amyloid aggregation by anti-seeding peptides may represent a disease mechanism and treatment target in ATTR amyloidosis, with an additional benefit over current therapies.