Primary Data on ATTR-Amyloidosis Prevalence Among Elderly Patients With Left Ventricular Hypertrophy in Russia.

AIM: To estimate the prevalence of amyloid cardiomyopathy (CM) caused by transthyretin amyloidosis (ATTR) and immunoglobulin light chain (AL) amyloidosis among patients aged >65 years with interventricular septal (IVS) hypertrophy of ≥14 mm. MATERIAL AND METHODS: From January through August 2023, 60 patients (mean age 7.2±7.3 years, 34 (56.67%) men) were enrolled. Patients meeting the inclusion criteria underwent an echocardiographic study with determining the myocardial longitudinal strain, myocardial scintigraphy with 99mTc-pyrfotech, myocardial single-photon emission computed tomography, measurement of N-terminal fragment of brain natriuretic peptide and troponin I, and the immunochemical study of serum and urine proteins with measurement of free light chains. In the presence of grades 2 and 3 radiopharmaceutical uptake according to scintigraphy, a molecular genetic study was performed for differential diagnosis of wild-type transthyretin amyloidosis (wtATTR) and hereditary/variant (hATTR) ATTR-CM. RESULTS: According to data of myocardial scintigraphy with 99mTc-pyrfotech, grade 3 uptake in the absence of monoclonal secretion was detected in 5 (8.3%) cases and grade 2 radiotracer uptake in the absence of monoclonal secretion was detected in 6 (10%) patients. Myeloma complicated by AL amyloidosis and primary AL amyloidosis were found in 5 (8.3%) patients. CONCLUSION: Among patients aged ≥65 years with IVS hypertrophy ≥14 mm, amyloid CM was detected in 20% of cases (12 patients), including 5 cases (8.3%) of AL amyloidosis and 7 cases (11.7%) of ATTR amyloidosis.

Epidemiology and clinical outcomes of light-chain amyloidosis in Sweden: A nationwide population-based study.

OBJECTIVES: This study evaluated data from six Swedish national registries to fill current evidence gaps on the epidemiology, clinical burden, and overall survival (OS) associated with light-chain (AL) amyloidosis. METHODS: Patients newly diagnosed with AL amyloidosis were identified using six linked Swedish nationwide population-based registers. For each case, individuals from the general population were selected and matched with a maximum ratio of 1:5 based on age, sex, calendar year, and county. RESULTS: 846 patients newly diagnosed with AL amyloidosis and 4227 demographically matched individuals were identified. From 2011 to 2019, annual AL amyloidosis incidence increased from 10.5 to 15.1 cases per million. At baseline, patients with AL amyloidosis had a significantly higher disease burden including higher rates of cardiac and renal failure relative to the comparison group. Among patients with AL amyloidosis, 21.5% had incident heart failure and 17.1% had incident renal failure after initial diagnosis. Median OS for patients with AL amyloidosis was 56 months versus not reached in the matched general population comparison group. CONCLUSION: The incidence of newly diagnosed AL amyloidosis in Sweden increased over time with AL amyloidosis being associated with a higher risk of cardiac/renal failure and all-cause mortality compared with the general population.

State-of-the-art review on AL amyloidosis in Western Countries: Epidemiology, health economics, risk assessment and therapeutic management of a rare disease.

Amyloidosis is the term to define a broad array of rare protein misfolding syndromes. Among them, light chain (AL) amyloidosis is the most common, affecting roughly 10 people per million/year. The core purpose of the present literature review is to shed light on the academic and clinical knowledge on the condition, encompassing its i) epidemiology, ii) economic burden, and iii) quality of life consequences. The areas of interest are Europe and North America. Literature search was primarily performed on Embase® and finally integrated with additional, deemed eligible, sources. Pre-defined PICOS criteria were employed for the inclusion and exclusion processes. A total of 64 studies were comprehensively included in the current literature review as compliant with the inclusion criteria. The results were presented according to the outcomes of interest and eventually triangulated and compared to available literature studies. A broad picture on the main aspects of AL amyloidosis is delivered.

A comprehensive overview of AL amyloidosis disease characteristics accumulated over two decades at a single referral center in Korea.

BACKGROUND: Characteristics of AL amyloidosis across Asia are not well-described in the literature. Thus, we overviewed the incidence and disease characteristics of AL amyloidosis in Korea. METHODS: We collected medical records of 302 AL amyloidosis patients and compared survival outcomes by predominant treatment strategy and at four time points: 1995-2003, 2004-2008, 2009-2013, and 2014-2018. RESULTS: The median age was 62 years (36-83). One hundred forty-one patients were classified as stage III (26.3%) or IV (47.9%). The patients diagnosed between 2014 and 2018 survived longer than those diagnosed at other time points due to the introduction of bortezomib (p < 0.01). In addition, patients who received upfront ASCT survived longer than those who received salvage ASCT or chemotherapy alone (p < 0.01). However, most of the 85 patients who experienced early death within 6 months were older than 75 years, had BMI less than 20, and had a high disease burden. CONCLUSIONS: The incidence of AL amyloid has increased and survival outcomes have improved gradually, most likely due to introduction of novel agents and upfront ASCT. However, not all patients are suitable for these potent treatment modalities, and avoiding early death within 6 months remains a challenge.

Real-world treatment patterns, costs, and outcomes in patients with AL amyloidosis: analysis of the Optum EHR and commercial claims databases.

BACKGROUND: This study characterised real-world treatment patterns, clinical outcomes, and cost-of-illness in patients with light-chain (AL) amyloidosis. METHODS: Data were extracted from the US-based Optum® EHR and Clinformatics® Data Mart (claims) databases (2008-2019) for patients newly diagnosed with AL amyloidosis and who initiated anti-plasma cell therapies. Healthcare resource utilisation (HCRU) and related costs were compared across lines of therapy (LOT). Incidences of cardiac and renal failure were evaluated using the Kaplan-Meier method. RESULTS: About 1347 patients (EHR, n = 776; claims, n = 571) were included. Median age was 68 years; 56.8% were male. At initial diagnosis, 33.1% and 15.1% of patients had cardiac and renal failure, respectively. Most patients received bortezomib-containing treatment in LOT1 (69%); bortezomib-cyclophosphamide-dexamethasone was most common (26%). HCRU was similar across LOTs. Mean per-patient-per-month and per-patient-per-LOT costs were $19,343 and $105,944 for LOT1, $19,183 and $95,793 for LOT2, and $16,611 and $128,446 for LOT3, respectively. Costs were primarily driven by anti-plasma cell therapies, outpatient visits, and hospitalisations. The 5-year cardiac and renal failure rates following initial diagnosis were 64.5% and 39.0%, respectively. CONCLUSION: AL amyloidosis is associated with substantial costs and suboptimal outcomes, highlighting the need for new therapeutic approaches to prevent organ deterioration, and reduce disease burden.

A population-based cohort study of the epidemiology of light-chain amyloidosis in Taiwan.

The incidence rate of AL (light-chain) amyloidosis is not known in Asia. We conducted a retrospective cohort study using the Taiwan National Healthcare Insurance Research database and Death Registry to estimate incidence and all-cause case fatality rates, and characteristics of patients with AL amyloidosis in Taiwan. All patients with confirmed, newly diagnosed AL amyloidosis from 01-Jan-2016 until 31-Dec-2019 were enrolled and followed up until dis-enrolment, death or study end (31-Dec-2019). There were 841 patients with newly diagnosed AL amyloidosis with median age of 61.4 years and 58.7% were men. At diagnosis, cardiac, renal and liver-related diseases were present in 28.54%, 23.19% and 2.14% of patients, respectively. AL amyloidosis age-adjusted annual incidence was 5.73 per million population in 2016 and 5.26 per million population in 2019. All-cause case fatality ranged from 1.7 to 2.9% over the study period and was highest (~10%) in patients ≥ 80 years. Survival was significantly lower in patients with co-morbid cardiac, renal, or liver-related diseases which could indicate organ involvement. The incidence of AL amyloidosis in Taiwan appears to be similar to Western countries. The poor prognosis in patients with co-morbid diseases highlights the need for earlier diagnosis.

Prevalence and predictors of neurological manifestations in systemic AL amyloidosis.

INTRODUCTION: Immunoglobulin light chain (AL) amyloidosis is a life-threatening systemic disease due to plasma cell dyscrasias, which is characterized by amyloid deposition in various tissues. Neurological manifestations, in particular peripheral nervous system involvement, play a major role for quality of life and treatment decisions as frequently potentially neurotoxic drugs are used. METHODS: We retrospectively investigated the prevalence of neurological manifestations, its risk factors and prognostic value in 155 consecutive patients with AL amyloidosis in a single German tertiary center between 2010 and 2021. Multiple logistic regression was performed to identify predictors of amyloid neuropathy and the impact of peripheral neuropathy on patient survival was assessed by Cox proportional hazard regression analysis. RESULTS: Nearly half of patients showed at least one of four neurological manifestations of AL amyloidosis which were frequent in our study: peripheral neuropathy (36.8%), carpal tunnel syndrome (12.9%), lumbar spinal stenosis (7.1%), and amyloid myopathy (3.9%). Male sex (OR 2.943, CI 1.152-8.139, p = 0.029) and cardiac involvement (OR 6.186, CI 1.449-43.38, p = 0.028) were independent predictors of peripheral neuropathy which was closely related to autonomic dysfunction in patients with AL amyloidosis. Peripheral neuropathy had no impact on survival (HR 0.952, CI 0.517-1.754, p = 0.876). CONCLUSIONS: Neurological involvement is common in systemic AL amyloidosis. Treatment decisions should take into account peripheral neuropathy, in particular in male patients with amyloid cardiomyopathy, but also amyloid myopathy that seems to be not as rare as previously suggested.

Hypovitaminosis D Is Prevalent in Patients With Renal AL Amyloidosis and Associated With Renal Outcome.

Introduction: Vitamin D deficiency is common, but no data have been reported on vitamin D levels in light chain (AL) amyloidosis. Patients and Methods: In this exploratory study, stored serum samples from 173 patients with newly diagnosed AL amyloidosis were analyzed for vitamin studies which included 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D] and vitamin D binding protein (DBP). Measurements were made by liquid chromatography-tandem mass spectrometry. Kidney survival and overall survival (OS) were assessed in association to vitamin D status. Results: Cardiac and kidney involvement occurred in 69% and 63% of patients, respectively. 25(OH)D deficiency (<20 ng/mL) was seen in 56.6% of the patients and was notably found among patients with heavy proteinuria (96%), hypoalbuminemia (84.3%) and morbidly obese patients (68.3%). Heavy proteinuria (>5 gr/24-h) and vitamin D supplementation were independent predictors of 25(OH)D level on nominal multivariate regression analysis. 1,25(0H)2D deficiency was noted in 37.6% of patients and was independently associated with low eGFR and hypoalbuminemia. Progression to ESRD occurred in 23.7% of evaluable patients. Patients who progressed to ESRD had lower serum 25(OH)D and 1,25(OH)2D levels compared to those who did not progress to ESRD. On a multivariate analysis, severe 25(OH)D deficiency was an independent predictor of progression to ESRD as was renal stage, while 1,25(OH)2D deficiency was not. Conclusions: Hypovitaminosis D is common in AL amyloidosis, particularly among patients with heavy proteinuria. Severe 25(OH)D deficiency at time of diagnosis predicts progression to ESRD.

Prevalence, clinical characteristics and treatment outcome of factor X deficiency in a consecutive cohort of primary light-chain amyloidosis.

Factor X (FX) deficiency is prevalent in light-chain (AL) amyloidosis but its clinical significance was not investigated deeply. We conducted a retrospective analysis of a consecutive cohort with 207 primary AL amyloidosis patients. FX deficiency was present in 129 patients (62.3%). Those with FX deficiency had higher dFLC (299.6 mg/L vs. 102.3 mg/L, P < 0.001), higher cardiac troponin I (0.05 µg/L vs. 0.02 µg/L, P < 0.001) and N-terminal pro-brain natriuretic peptide (3115 ng/L vs. 392 ng/L, P < 0.001), and more patients with bone marrow plasma cells > 10% (18.0% vs. 4.3%, P = 0.008). The prevalence of FX deficiency increased with the Mayo 2004 stage. FX-deficient patients exhibited inferior overall survival (P < 0.001) and progression-free survival (P < 0.001) than others. Fifty-five patients with FX deficiency received retesting of FX activity after anti-plasma cell therapy. The median variation in FX activity was + 6.8% (range, -24.5% ~ +73.4%). Better improvement of FX activity was observed in patients with complete hematologic response (+18.2% vs. +4.0%, P = 0.036) and at least one organ response (+14.4% vs. +3.4%, P = 0.024). FX deficiency is associated with a heavier disease burden and poorer survival in primary AL amyloidosis. Improvement of FX activity tends to appear in patients with better hematologic and organ responses after chemotherapy.

Global epidemiology of amyloid light-chain amyloidosis.

BACKGROUND: Amyloid light-chain (AL) amyloidosis is an ultra-rare disease associated with significant morbidity and mortality. Few studies have examined the global epidemiology of this condition. METHODS: This study estimated the diagnosed incidence and 1-year, 5-year, 10-year, and 20-year period prevalence of AL amyloidosis in 2018 for countries in and near Europe, and in the United States (US), Canada, Brazil, Japan, South Korea, Taiwan, and Russia. A systematic literature review (SLR) was conducted to identify country-specific, age- and gender-specific diagnosed incidence of AL amyloidosis and observed survival data-point inputs for an incidence-to-prevalence model. Extrapolations were used to estimate incidence and prevalence for countries without registry or published epidemiological data. RESULTS: Of 171 publications identified in the SLR, 10 records met the criteria for data extraction, and two records were included in the final incidence-to-prevalence model. In 2018, an estimated 74,000 AL amyloidosis cases worldwide were diagnosed during the preceding 20 years. The estimated incidence and 20-year prevalence rates were 10 and 51 cases per million population, respectively. CONCLUSIONS: Orphan medicinal product designation criteria of the European Medicines Agency or Electronic Code of Federal Regulations indicate that a disease must not affect > 5 in 10,000 people across the European Union or affect < 200,000 people in the US. This study provides up-to-date epidemiological patterns of AL amyloidosis, which is vital for understanding the burden of the disease, increasing awareness, and to further research and treatment options.

Cardiac amyloidosis-interdisciplinary approach to diagnosis and therapy.

The vast majority of cardiac amyloidosis (CA) cases are caused by light chain (AL) or transthyretin (ATTR) amyloidosis. The latter is divided into hereditary (ATTRv) and wild-type forms (ATTRwt). The incidence of ATTRwt amyloidosis has significantly increased, particularly due to the improved diagnosis of cardiac manifestations, with relevant proportions in patient populations with heart failure (HF) and preserved ejection fraction (HFpEF). Cardiac amyloidosis should be suspected in HF with indicative clinical scenarios/"red flags" with typical signs of CA in echocardiography. Further noninvasive imaging (cardiovascular magnetic resonance imaging, scintigraphy) and specific laboratory diagnostics are important for the diagnosis and typing of CA into the underlying main forms of ATTR and AL amyloidosis. The histopathologic analysis of an endomyocardial biopsy is necessary if noninvasive diagnostic methods do not enable reliable typing of CA. This is crucial for initiating specific therapy. Therapy of HF in CA is largely limited to the use of diuretics in the absence of evidence on the benefit of classic HF therapy with neurohormonal modulators. Innovative therapies have been developed for amyloidosis with improvement in organ protection, prognosis, and quality of life. These include specific cytoreductive therapies for monoclonal light-chain disease in AL amyloidosis and pharmacologic stabilization or inhibition of transthyretin expression in ATTR amyloidosis. Since the CA underlying amyloidosis is a systemic disease also affecting other organ systems, close interdisciplinary cooperation is crucial for rapid and effective diagnosis and therapy.

Prevalence of plasma cell and lymphoproliferative disorders among blood relatives of patients with light chain amyloidosis.

With limited existing data on hereditary factors in light chain (AL) amyloidosis, we conducted a study of patients with plasma cell dyscrasias or lymphoproliferative disorders in their family history. Among 1621 patients, we identified 44 probands (2·7%) with 52 relatives affected. The most common disorders in family members were multiple myeloma (48%) and AL amyloidosis (18%). Light chain isotype was 100% congruent in families with known clonal immunoglobulin for both members. Despite matching light chain isotype, organ involvement varied between members in families with multiple cases of AL amyloidosis. These findings help generate hypotheses about familial influences in AL amyloidosis.

Light Chain Amyloidosis: Epidemiology, Staging, and Prognostication.

Amyloidosis is a disorder of protein misfolding and metabolism in which insoluble fibrils are deposited in various tissues, causing organ dysfunction and eventually death. Out of the 60-plus heterogeneous amyloidogenic proteins that have been identified, approximately 30 are associated with human disease. The unifying feature of these proteins is their tendency to form beta-pleated sheets aligned in an antiparallel fashion. These sheets then form rigid, nonbranching fibrils that resist proteolysis, causing mechanical disruption and local oxidative stress in affected organs such as the heart, liver, kidneys, nervous system, and gastrointestinal tract. Here we review the epidemiology of light chain amyloidosis, the staging, and the concomitant prognostication that is critical in determining the appropriate treatment.

Clinical features and predictors of atrial fibrillation in patients with light-chain or transthyretin cardiac amyloidosis.

AIMS: The study aimed to investigate the prevalence, phenotypic characteristics, and predictors of atrial fibrillation (AF) in patients presenting with cardiac amyloidosis (CA) of light-chain (AL) or transthyretin (ATTR) type. METHODS AND RESULTS: Clinical, biochemical, and echocardiographic data of patients presenting with CA between 2005 and 2020 were retrospectively collected. CA staging was based on established biomarker systems. Binomial logistic regression was run to analyse the effects of clinical variables on the likelihood of AF. The study included 133 patients [53% AL, 41% wild-type (wt) ATTR-CA, & 6% hereditary ATTR-CA]. Mean age was 71 years, and 80% were male patients. AF was diagnosed in 64 (48%) patients (28% in AL-CA, 80% in wtATTR, 13% in hATTR, P < 0.001). Patients with AF were older (74 vs. 69 years, P < 0.001), more likely to have wtATTR-CA (67 vs. 16%, P < 0.001), exhibited more often New York Heart Association ≥ III symptoms (66 vs. 45%, P = 0.02) and carried a higher burden of comorbidities. AF patients had lower left ventricular ejection fraction (47 vs. 53%, P < 0.005), higher left atrial volume index (54 vs. 46 mL/m2 , P = 0.007), higher pulmonary artery pressure (42 vs. 31 mmHg, P = 0.008), and worse tricuspid annular plane systolic excursion values (17 vs. 20 mm, P = 0.01). Mitral regurgitation ≥ Grade 2 was more frequent in AF (56 vs. 25%, P < 0.001). Higher ATTR-CA stage was associated with higher AF prevalence (47% vs. 74% vs. 94%, P < 0.001, for Stages I, II, & III, respectively). Higher AL-CA stage was associated with lower AF prevalence (0% vs. 40% vs. 31% vs. 18%, P < 0.001, for Stages I, II, IIIa, & IIIb, respectively). Three independent predictors for AF were identified in a multivariate logistic regression model with 81.5% classification accuracy: AL type [odds ratio (OR) 0.1, confidence interval (CI) 0.01-0.29, P = 0.001], estimated glomerular filtration rate (OR 0.9, CI 0.93-0.99, P = 0.03), and body mass index (OR 1.3, CI 1.07-1.66, P = 0.01). ATTR amyloidosis was associated with a 10-fold higher risk of AF. During 1 year follow-up, only one episode of ischaemic stroke was reported. CONCLUSIONS: Atrial fibrillation affects nearly half of all patients with CA. Patients presenting with AF have more severe symptoms and higher burden of comorbidities. ATTR type of amyloidosis is the strongest predictor of AF. Prospective screening for occult AF may be considered in ATTR-CA.

Misconceptions and Facts About Cardiac Amyloidosis.

Cardiac amyloidosis is an important clinical entity associated with significant morbidity and mortality. Although the signs and symptoms can be apparent early in the disease course, diagnoses are often made late because of inadequate recognition. A diagnosis of cardiac amyloidosis requires careful scrutiny of a patient's symptoms, an electrocardiogram, and imaging studies, including echocardiography and magnetic resonance imaging. Further evaluation is required through the measurement of serum and urine light chains and the use of bone scintigraphy imaging to differentiate transthyretin amyloidosis from light-chain cardiac amyloidosis. The available treatments have expanded tremendously in recent years and have improved outcomes in the population with this disorder. Thus, it has become increasingly important to diagnose cardiac amyloidosis and provide timely therapies. This article will clarify the various misconceptions about cardiac amyloidosis and provide a framework for primary care providers to better identify this disease in their practice.

History of extracardiac/cardiac events in cardiac amyloidosis: prevalence and time from initial onset to diagnosis.

AIMS: Cardiac amyloidosis (CA) has a poor prognosis which is aggravated by diagnostic delay. Amyloidosis extracardiac and cardiac events (AECE and ACE) may help improve CA diagnosis and typing. The aim of this study was to compare AECE and ACE between different CA types and assess their relationship with survival. METHODS AND RESULTS: This retrospective cohort study conducted in France from June 2008 to May 2019, at the Henry Mondor Hospital. This cohort included 983 patients with CA. Mean age at inclusion was 73.1 ± 11.4 years, 726 (75.1%) were male and the mean body mass index was 24.5 ± 4.1 kg/m2 . Among them, 321 had immunoglobulin light chain (AL) amyloidosis, 434 had wild-type transthyretin (ATTRwt), and 212 had hereditary transthyretin (ATTRv). The first AECE and/or ACE occurred at a mean age of 63 ± 11 years for AL and ATTRv, and 70 ± 12 years for ATTRwt (P < 0.01). The median (Q1-Q3) delay between declaration of the first events and diagnosis varied from 11.1 (5.9; 34.8) months for AL to 92.2 (39.0; 174.7) months for ATTRwt (P < 0.01). The nature of the onset of AECE or ACE varied based on amyloidosis type, heart failure symptoms for AL (26%) and integumentary symptoms for ATTRv with cardiologic or mixed phenotype (39%) and ATTRwt (42%). In AL and ATTRwt, a short delay between the onset of the first AECE or ACE and diagnosis was associated with reduced survival rate (log-rank test P-value <0.01). CONCLUSIONS: This study highlights the impact of amyloidosis type and evolution on diagnostic delay and on prognosis. Physicians must be aware and vigilant in front of extracardiac and cardiac events to considerably improve early diagnosis of amyloidosis.

Marked progress in AL amyloidosis survival: a 40-year longitudinal natural history study.

The recent decades have ushered in considerable advancements in the diagnosis and treatment of systemic light chain (AL) amyloidosis. As disease outcomes improve, AL amyloidosis-unrelated factors may impact mortality. In this study, we evaluated survival trends and primary causes of death among 2337 individuals with AL amyloidosis referred to the Boston University Amyloidosis Center. Outcomes were analyzed according to date of diagnosis: 1980-1989 (era 1), 1990-1999 (era 2), 2000-2009 (era 3), and 2010-2019 (era 4). Overall survival increased steadily with median values of 1.4, 2.6, 3.3, and 4.6 years for eras 1-4, respectively (P < 0.001). Six-month mortality decreased over time from 23% to 13%. Wide gaps in survival persisted amid patient subgroups; those with age at diagnosis ≥70 years had marginal improvements over time. Most deaths were attributable to disease-related factors, with cardiac failure (32%) and sudden unexpected death (23%) being the leading causes. AL amyloidosis-unrelated mortality increased across eras (from 3% to 16% of deaths) and with longer-term survival (29% of deaths occurring >10 years after diagnosis). Under changing standards of care, survival improved and early mortality declined over the last 40 years. These findings support a more optimistic outlook for patients with AL amyloidosis.

Haematologic responses and survival do not significantly decrease with subsequent lines of therapy in systemic immunoglobulin light chain amyloidosis: results from an analysis of real-world longitudinal data.

Systemic immunoglobulin light chain amyloidosis (AL) is an incurable disorder, and the natural history is incompletely understood. In this study, we describe its natural history based on an analysis of real-world longitudinal data. All patients seen at the National Amyloidosis Centre, UK, between February 2010 and August 2019 and treated with up-front bortezomib are included. In all, 1 276 patients received the first-line treatment; 259, 85, and 32 patients received second, third, and fourth treatment lines, respectively. Among patients requiring further treatment after the first line, 77·2% started the second line within two years of the first line; 50·5%, 50·6%, 40·1% and 40·6% of patients had achieved at least very good partial response after the first, second, third and fourth treatment lines. Median overall survival (OS) from first, second, third and fourth lines was 45 months, 56 months, 37 months and not reached, respectively (P = 0·109). In summary, although relapses occur in AL amyloidosis, the outcomes and responses do not worsen with each subsequent relapse, making it attractive to design therapeutics with curative intent.

Emerging therapy in light-chain and acquired transthyretin-related amyloidosis: an Italian single-centre experience in heart transplantation.

AIMS: The prognosis for patients affected by light-chain cardiac amyloidosis and acquired transthyretin-related (TTR) amyloidosis is poor. Heart transplantation (HTx) could improve prognosis also enabling autologous stem cell transplantation (ASCT) in the first group. METHODS AND RESULTS: A total of 36 patients affected by systemic amyloidosis have been referred to our centre from 2009 to 2019. Of these, nine had cardiac involvement: seven by light-chain amyloidosis and two by acquired TTR amyloidosis. None died while waiting for HTx. A specific internal protocol useful to select candidates and to monitor the organ involvement after HTx was developed. Median age at diagnosis was 54 years and 66% were male. The most common short-term complication after HTx was renal failure (44%), followed by acute cardiac rejection more than 2R (22%). ASCT was performed in six out of seven light-chain cardiac amyloidosis patients, with a median time of 6 months after HTx. Two patients affected by light-chain cardiac amyloidosis died due to amyloidosis relapse: one before undergoing ASCT. After a median follow-up of 31 (7-124) months, 1- and 5-year survival was 88 and 66% in the cardiac light-chain amyloidosis group. Conversely, 1- and 5-year survival was 100% in the acquired TTR amyloidosis group. CONCLUSION: HTx may represent a valuable option in carefully selected patients. ASCT after HTx is an effective treatment that could decrease amyloidosis relapse in light-chain cardiac amyloidosis patients. A multidisciplinary approach is mandatory to select the best candidates and to obtain the most effective results with a specific surveillance follow-up protocol.