Prevalence, Characteristics, and Impact on Prognosis of Aortic Stenosis in Patients With Cardiac Amyloidosis.

BACKGROUND: Cardiac amyloidosis (CA) is frequently found in older patients with aortic stenosis (AS). However, the prevalence of AS among patients with CA is unknown. The objective was to study the prevalence and prognostic impact of AS among patients with CA. METHODS AND RESULTS: We conducted a retrospective analysis of a prospective registry comprising 976 patients with native aortic valves who were confirmed with wild type transthyretin amyloid (ATTRwt), hereditary variant transthyretin amyloid (ATTRv), or immunoglobulin light-chain (AL) CA. CA patients' echocardiograms were re-analyzed focusing on the aortic valve. Multivariable Cox regression analysis was performed to assess the mortality risk associated with moderate or greater AS in ATTRwt CA. The crude prevalence of AS among patients with CA was 26% in ATTRwt, 8% in ATTRv, and 5% in AL. Compared with population-based controls, all types of CA had higher age- and sex-standardized rate ratios (SRRs) of having any degree of AS (AL: SRR, 2.62; 95% Confidence Interval (CI) [1.09-3.64]; ATTRv: SRR, 3.41; 95%CI [1.64-4.60]; ATTRwt: SRR, 10.8; 95%CI [5.25-14.53]). Compared with hospital controls, only ATTRwt had a higher SRR of having any degree of AS (AL: SRR, 0.97, 95%CI [0.56-1.14]; ATTRv: SRR, 1.27; 95%CI [0.85-1.44]; ATTRwt: SRR, 4.01; 95%CI [2.71-4.54]). Among patients with ATTRwt, moderate or greater AS was not associated with increased all-cause death after multivariable adjustment (hazard ratio, 0.71; 95%CI [0.42-1.19]; P=0.19). CONCLUSIONS: Among patients with CA, ATTRwt but not ATTRv or AL is associated with a higher prevalence of patients with AS compared with hospital controls without CA, even after adjusting for age and sex. In our population, having moderate or greater AS was not associated with a worse outcome in patients with ATTRwt.

Patients with a cardiac complete response in AL amyloidosis have survival rates similar to those of a matched general population.

ABSTRACT: The survival of patients achieving a cardiac complete response in light chain amyloidosis, defined as N-terminal pro B-type natriuretic peptide ≤350 pg/mL or B-type natriuretic peptide ≤80 pg/mL, was similar to that of a matched general population, with estimated 5-year survival rates of 93% and 95%, respectively.

Safety and efficacy of levosimendan in patients with cardiac amyloidosis.

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.

Thrombotic and bleeding complications in patients with AL amyloidosis.

Haemostatic abnormalities and deregulated coagulation are common complications in AL amyloidosis. The relevant risks of thromboembolic and haemorrhagic events have not been thoroughly evaluated. To describe clinically significant thrombotic/haemorrhagic events in 450 consecutive patients with AL amyloidosis. Venous thromboembolic events (VTEs) were reported in 6% and arterial embolic events (AEEs) in 5% of patients, respectively, during a 55-month median follow-up. Lower albumin, lower eGFR, higher BM infiltration, soft tissue involvement, IMiD-based therapy and prior thrombosis were associated with VTE risk. Prior thrombosis was the only independent prognostic variable (HR 9.3, p = 0.001). Coronary arterial disease, prior AEE, 24-h proteinuria and higher platelet counts were associated with AEE risk. Significant bleeding events were reported in 9%, and associated mortality was 19%. Liver involvement, higher serum creatinine and higher baseline VWF:Ag levels were linked to bleeding risk. Using competing risk analysis, the cumulative probability of thrombosis/bleeding was higher during the first year following diagnosis, but a stable lower risk for both events remained for the duration of follow-up. In AL amyloidosis patients, the risk of thrombotic/arterial embolic events is significant, but the bleeding risk is also high. A multiparametric assessment is required to initiate anti-thrombotic or anti-platelet therapy appropriately.

Prognostic value of the tricuspid annular plane systolic excursion/systolic pulmonary artery pressure ratio in cardiac amyloidosis.

INTRODUCTION AND OBJECTIVES: The tricuspid annular plane systolic excursion/systolic pulmonary artery pressure (TAPSE/SPAP) ratio is a noninvasive surrogate of right ventricular to pulmonary circulation that has prognostic implications in patients with heart failure (HF) or pulmonary hypertension. Our purpose was to evaluate the prognostic value of the TAPSE/SPAP ratio in patients with cardiac amyloidosis. METHODS: We used the database of the AMIGAL study, a prospective, observational registry of patients with cardiac amyloidosis recruited in 7 hospitals of the Autonomous Community of Galicia, Spain, from January 1, 2018 to October 31, 2022. We selected patients whose baseline TAPSE/SPAP ratio was calculated with transthoracic echocardiography. Long-term survival and survival free of HF hospitalization were assessed by means of 5 different multivariable Cox regression models. Median follow-up was 680 days. RESULTS: We studied 233 patients with cardiac amyloidosis, among whom 209 (89.7%) had transthyretin type. The baseline TAPSE/SPAP ratio correlated significantly with clinical outcomes. Depending on the multivariable model considered, the adjusted hazard ratios estimated per 0.1mm/mmHg increase of baseline TAPSE/SPAP ratio ranged from 0.76 to 0.84 for all-cause mortality. Similarly, the ratios for all-cause mortality of HF hospitalization ranged from 0.79 to 0.84. The addition of the baseline TAPSE/SPAP ratio to the predictive model of the United Kingdom National Amyloidosis Centre resulted in an increase in Harrell's c-statistic from 0.662 to 0.705 for all-cause mortality and from 0.668 to 0.707 for all-cause mortality or HF hospitalization. CONCLUSIONS: Reduced TAPSE/SPAP ratio is an independent adverse prognostic marker in patients with cardiac amyloidosis.

Left ventricular myocardial work improves in response to treatment and is associated with survival among patients with light chain cardiac amyloidosis.

AIMS: Complete haematologic response to treatment for light chain cardiac amyloidosis (AL-CA) may lead to improvement of myocardial function and better outcomes. We sought to evaluate the effect of response to treatment for AL-CA on echocardiographic indices of myocardial deformation and work and their prognostic significance. METHODS AND RESULTS: Sixty-one patients treated for AL were enrolled and underwent echocardiographic assessment at baseline and at 1 year. Patients were stratified according to haematologic response as complete or not complete responders. A significant reduction in median N-terminal pro-brain natriuretic peptide (NT-proBNP) (2771-1486 pg/mL; P < 0.001) and posterior wall thickness (13-12 mm; P = 0.002) and an increase in global work index (GWI) (1115-1356 mmHg%; P = 0.018) was observed at 1 year. Patients with complete response (CR) had a more pronounced decrease in intraventricular septum thickness (14.2-12.0 mm; P = 0.006), improved global longitudinal strain (GLS) (-11.6 to -13.1%; P for interaction = 0.045), increased global constructive work (1245-1436 mmHg%; P = 0.008), and GWI (926-1250 mmHg%, P = 0.002) compared with non-CR. Furthermore, deltaGLS (ρspearman = 0.35; P < 0.001) and deltaGWI (ρspearman = -0.32; P = 0.02) correlated with delta NT-proBNP. Importantly, patients with GLS and GWI response had a better prognosis (log-rank P = 0.048 and log-rank P = 0.007, respectively). After adjustment for Mayo stage, gender, and response status, deltaGLS [hazard ratio (HR) = 1.404, P = 0.046 per 1% increase] and deltaGWI (HR = 0.996, P = 0.042 per 1mmHg% increase) were independent predictors of survival. CONCLUSION: Complete haematologic response to treatment is associated with improved left ventricular myocardial work indices, and their change is associated with improved survival in AL-CA.

Clinical outcomes and survival in AA amyloidosis patients / Desfechos clínicos e sobrevida em pacientes com amiloidose AA

Abstract Aim Amyloid A amyloidosis is a rare complication of chronic inflammatory conditions. Most patients with amyloid A amyloidosis present with nephropathy and it leads to renal failure and death. We studied clinical characteristics and survival in patients with amyloid A amyloidosis. Methods: A total of 81 patients (51 males, 30 females) with renal biopsy proven amyloid A amyloidosis were analyzed retrospectively. The patients were divided into good and poor outcomes groups according to survival results. Results: Most of the patients (55.6%) had nephrotic range proteinuria at diagnosis. Most frequent underlying disorders were familial Mediterranean fever (21.2%) and rheumatoid arthritis (10.6%) in the good outcome group and malignancy (20%) in the poor outcome group. Only diastolic blood pressure in the good outcome group and phosphorus level in the poor outcome group was higher. Serum creatinine levels increased after treatment in both groups, while proteinuria in the good outcome group decreased. Increase in serum creatinine and decrease in estimated glomerular filtration rate of the poor outcome group were more significant in the good outcome group. At the time of diagnosis 18.5% and 27.2% of all patients had advanced chronic kidney disease (stage 4 and 5, respectively). Median duration of renal survival was 65 ± 3.54 months. Among all patients, 27.1% were started dialysis treatment during the follow-up period and 7.4% of all patients underwent kidney transplantation. Higher levels of systolic blood pressure [hazard ratios 1.03, 95% confidence interval: 1-1.06, p = 0.036], serum creatinine (hazard ratios 1.25, 95% confidence interval: 1.07-1.46, p = 0.006) and urinary protein excretion (hazard ratios 1.08, 95% confidence interval: 1.01-1.16, p = 0.027) were predictors of end-stage renal disease. Median survival of patients with organ involvement was 50.3 ± 16 months. Conclusion Our study indicated that familial Mediterranean fever constituted a large proportion of cases and increased number of patients with idiopathic amyloid A amyloidosis. Additionally, it was observed that patient survival was not affected by different etiological causes in amyloid A amyloidosis.

Resumo Objetivo: A amiloidose AA é uma complicação rara de condições inflamatórias crônicas. A maior parte dos pacientes com amiloidose AA apresenta nefropatia, que leva à insuficiência renal e à morte. Estudaram-se as características clínicas e a sobrevida em pacientes com amiloidose AA. Métodos: Analisaram-se retrospectivamente 81 pacientes (51 homens, 30 mulheres) com amiloidose AA comprovada por biópsia renal. Os pacientes foram divididos em grupos de desfecho bom e ruim de acordo com os resultados de sobrevida. Resultados: A maior parte dos pacientes (55,6%) tinha proteinúria na faixa nefrótica no momento do diagnóstico. Os distúrbios subjacentes mais frequentes foram a febre familiar do Mediterrâneo (FFM, 21,2%) e a artrite reumatoide (10,6%) no grupo de desfecho bom e a malignidade (20%) no grupo de desfecho ruim. Somente a pressão arterial diastólica no grupo de desfecho bom e o nível de fósforo no grupo de desfecho ruim foram mais elevados. Os níveis séricos de creatinina aumentaram após o tratamento em ambos os grupos, enquanto a proteinúria diminuiu no grupo de desfecho bom. O aumento na creatinina sérica e a diminuição na TFGe do grupo de desfecho ruim foram mais significativos no grupo de desfecho bom. No momento do diagnóstico, 18,5% e 27,2% de todos os pacientes tinham doença renal crônica avançada (estágios 4 e 5, respectivamente). A duração média da sobrevida renal foi de 65 ± 3,54 meses. Entre todos os pacientes, 27,1% iniciaram tratamento de diálise durante o período de seguimento e 7,4% de todos os pacientes foram submetidos a transplante renal. Níveis elevados de pressão arterial sistólica [taxas de risco (HR) 1,03, intervalo de confiança (IC) de 95%: 1 a 1,06, p = 0,036], creatinina sérica (HR 1,25, IC 95%: 1,07 a 1,46, p = 0,006) e excreção urinária de proteínas (HR 1,08, IC 95%: 1,01 a 1,16, p = 0,027) foram preditores de doença renal terminal. A mediana da sobrevida de pacientes com comprometimento de órgãos foi de 50,3 ± 16 meses. Conclusão: O presente estudo indicou que a FFM constituiu uma grande proporção de casos e crescente quantidade de pacientes com amiloidose AA idiopática. Adicionalmente, observou-se que a sobrevida do paciente não foi afetada pelas diferentes causas etiológicas na amiloidose AA.

Amiloidosis: enfermedad desafiante en su diagnóstico y tratamiento / Amyloidosis: diagnosis and treatment

La amiloidosis es una enfermedad sistémica caracterizada por el depósito de fibrillas amiloídeas en diversos órganos, lo que lleva a un deterioro y falla progresiva de éstos, afectando sustancialmente la sobrevida del paciente. Se analizaron los registros médicos de 34 pacientes egresados con diagnóstico de amiloidosis del Hospital Clínico de la Universidad de Chile en un período de 15 años. El promedio del tiempo entre la aparición de síntomas y el diagnóstico fue aproximadamente de seis meses. Los compromisos sistémicos de mayor relevancia fueron el renal y cardíaco, influyendo este último notablemente en la sobrevida. El laboratorio inmunológico tuvo un rol fundamental en identificar a los pacientes portadores de una paraproteína y de esta manera apoyar el diagnóstico. Es necesario plantearse este diagnóstico diferencial en todo paciente con compromiso sistémico de causa no clara y más aún cuando está asociado un trastorno mieloproliferativo.

Amyloidosis is a systemic disease characterized by the deposition of amyloid fibrils in many organs, leading to a progressive deterioration and failure of these, substantially affecting the survival of the patient. We present 34 medical records of patients that were hospitalized with the diagnosis of amyloidosis in the Hospital of the Universidad de Chile, over a period of fifteen years. The average time between the onset of symptoms and diagnosis was approximately six months. The most important systemic affectations were to the kidney and heart, the latter significantly influences survival. The immunology laboratory plays a fundamental role in identifying patients with paraprotein, thus supporting diagnosis. It is necessary to consider this differential diagnosis in all patients with systemic symptoms of no clear cause, especially when it is associated to a myeloproliferative disorder.

Afectación renal en la amiloidosis. Características clínicas, evolución y supervivencia / Renal involvement in amyloidosis. Clinical outcomes, evolution and survival

Fundamento: La amiloidosis es una enfermedad sistémica caracterizada por eldepósito extracelular de material proteico fibrilar en disposición en lámina betaplegada. Las principales formas de amiloidosis sistémicas son la amiloidosis primaria(AL) y la secundaria (AA). La afectación renal es frecuente, confiriéndoleun pronóstico poco favorable. En los últimos años estamos asistiendo a un cambioen la etiología de las formas secundarias.Objetivo: Analizar la incidencia de AL y AA en nuestra área de referencia así comola etiología de AA. Describir la presentación clínica, la afectación renal y la evolución.Material y métodos: Análisis descriptivo de los casos de amiloidosis de nuestrohospital en el período 1992-2004. Criterio diagnóstico: histología positiva para RojoCongo. Se analizan las variables clínicas, afectación renal, inclusión en diálisis ysupervivencia.Resultados: Setenta y seis casos, 44 mujeres, edad media 70,7 ± 12. Tipos: 55AA (72%), 21 AL (28%), etiología AA: 66% reumatológicas, 28% infecciosas, 6%otras. La incidencia fue: AL 4,6 y AA 12,2 casos /millón. El 75% tenían afectaciónrenal al diagnóstico (69% ClCreat 3 g/24horas). 21 casos (28%) evolucionaron a insuficiencia renal grado V en un tiempomedio de 8,1 ± 9,8 meses, iniciando diálisis 14 pacientes (10 HD, 4 CAPD).En 7 casos (33%) no recibieron tratamiento dialítico por la importante afectacióndel estado general y la mala calidad de vida. La supervivencia actuarial globaldesde el momento del diagnóstico fue de 55% y 40% a los 12 y 24 meses (AL58% y 19%; AA 55% y 44%). La supervivencia actuarial desde el inicio de diálisisfue de 30% y 5% a los 12 y 24 meses.Conclusiones: Aunque la amiloidosis es una patología con escasa incidencia enla población general, la afectación renal es muy frecuente. Las enfermedades reumatológicasson la principal causa de AA. La supervivencia es limitada, especialmentepara las formas AL

Background: Systemic amyloidosis is a disease resulting from extracellular depositionof fibrillar protein in various organs. Main systemic amyloidosis are: primary (AL) and Secondary (AA). The kidney is usually involved, conferring and adverseprognosis. In the last decade there has been a change in the aetiology ofAA amyloidosis.Objectives: To analyse the incidence of AL and AA amyloidosis in our currentpopulation as well as the aetiology of AA amyloidosis. To describe clinical outcomes,renal involvement and survival.Patients and methods: We performed a descriptive analysis of all cases of amyloidosisdiagnosed from 1992 to 2004 in our hospital. Diagnosis was assessed onhistological criteria: positivity Congo Red stain. Clinical data, renal involvement,dialysis treatment and survival were analysed.Results: 76 cases, 44 women, mean age 70.7 ± 12. Types: 55 AA (72%), 21AL (28%) systemic amyloidosis. AA aetiology was: 66% rheumatic disorders, 28%infectious disease, 6% others. Incidence for AL was 4.6 and for AA 12.2 cases/million. Renal involvement was present in 75% at diagnosis (69% Creatinine clearance 3 g/24 hours). 21 cases (28%) progressedto renal disease stage V in the 8.1 ± 9.8 months follow up period, and14 cases started dialysis treatment (10 HD, 4 CAPD). In 7 cases (33%) dialysiswas not indicated due to their poor clinical condition, short life expectancy andbad quality of life. Mean global survival at diagnosis was 55% and 40% at 12and 24 months (AL 58% and 19%; AA 55% and 44%). Mean survival from thestart of dialysis was 30% and 5% at 12 and 24 months.Conclusions: Although amyloidosis has a low incidence in our population, thekidney is usually involved. Rheumatological disorders are the principal aetiologyof AA amyloidosis. Long term survival is poor, specially for AL

Fiebre mediterránea familiar: revisión de literatura / Familial mediterranean fever: review of the literature

La Fiebre mediterránea familiar corresponde a una enfermedad inflamatoria, de herencia autosómica recesiva, caracterizada por episodios febriles y serotisis, descrita mayoritariamente en grupos étnicos originarios de la costa mediterránea. La amiloidosis secundaria es la principal causa de mortalidad. El estudio de la mutación genética causante de esta enfermedad es útil para el diagnóstico, de no estar disponible, una prueba terapéutica con Colchicina es una herramienta valiosa. El uso de ésta droga es el tramiento de elección.

Amiloidosis hepática asociada a colestasis intrahepática severa: presentación de un caso / Hepatic amyloidosis presenting as severe intrahepatic cholestasis

El compromiso del hígado es frecuente en todas las formas de Amiloidosis pero las manifestaciones clínicas y bioquímicas de alteración en la función hepática son inusuales siendo la colestasis una forma extremadamente rara. Presentamos el caso de un paciente masculino de 67 años en quien se diagnosticó amiloidosis hepática asociada a mieloma que cursó con colestasis severa

Amiloidosis primaria con compromiso oseo a nivel de columna vertebral, hepatomegalia y polineuropatía

Describimos el caso de una paciente con amiloidosis sistémica adquirida, quien presentó compromiso de la columna lumbar con lesiones líticas y fracturas de cuerpos vertebrales por invasión amiloide, polineuropatía documentada por electromiografía y hepatomegalia evidenciada por gamagrafía y examen físico. El compromiso directo de hueso se corroboró por biopsia de L4. La paciente se ha manejado con colchicina fundamentalmente y en la actualidad tiene supervivencia de 12 años y se encuentra en buen estado general. Es el primer caso en la literatura médica confirmado de affeción de columna lumbar por amiloidosis.