Transthyretin Cardiac Amyloidosis in Australia and New Zealand-A Multi-Site Snapshot for 2022.

Objective: To estimate the burden of transthyretin cardiac amyloidosis (ATTR-CA) through a cross- sectional 'snapshot' of Australian Amyloidosis Network (AAN) and New Zealand (NZ) specialist amyloidosis clinics.

Design, Setting & Participants: A prospective survey was performed of seven AAN/ specialist amyloidosis clinics across Australia and NZ. All centres were invited to contribute data; participating centres provided clinical and demographic data for patients with ATTR-CA reviewed in the 2022 calendar year.

2024 Australia-New Zealand Expert Consensus Statement on Cardiac Amyloidosis.

Over the past 5 years, early diagnosis of and new treatments for cardiac amyloidosis (CA) have emerged that hold promise for early intervention. These include non-invasive diagnostic tests and disease modifying therapies. Recently, CA has been one of the first types of cardiomyopathy to be treated with gene editing techniques.

Kidney outcomes and prognostic factors of myeloma associated acute kidney injury in the contemporary era.

Myeloma cast nephropathy (MCN) has historically been associated with poor kidney outcomes. We aimed to evaluate the kidney outcomes and identify prognostic factors of myeloma-associated acute kidney injury (M-AKI) in the contemporary era of anti-plasma cell therapy. Patients who received anti-myeloma therapy with M-AKI (January 2012 to June 2020) from a single centre were identified from electronic medical records.

Current approaches to the diagnosis and management of amyloidosis.

Amyloidosis is a collection of diseases caused by the misfolding of proteins that aggregate into insoluble amyloid fibrils and deposit in tissues. While these fibrils may aggregate to form insignificant localised deposits, they can also accumulate in multiple organs to the extent that amyloidosis can be an immediately life-threatening disease, requiring urgent treatment. Recent advances in diagnostic techniques and therapies are dramatically changing the disease landscape and patient prognosis.

Lenalidomide and dexamethasone for systemic AL amyloidosis following prior treatment with thalidomide or bortezomib regimens.

The outcomes and responses to treatment remain poorly studied among patients with systemic AL amyloidosis who require further treatment following prior novel agent-based therapy. We report here treatment with lenalidomide-dexamethasone in 84 AL amyloidosis patients with relapsed/refractory clonal disease following prior treatment with thalidomide (76%) and/or bortezomib (68%). On an intention-to-treat (ITT) basis, the overall haematological response rate was 61%, including 20% complete responses.

A rare case of localised oral amyloid of the labial mucosa.

Amyloidosis is often a systemic process, and localised oral amyloidosis is rare. We present the case of a young woman with amyloid deposition in the labial mucosa of her lower lip. Systemic involvement was excluded by comprehensive assessment at the UK Amyloidosis Centre.

CMR-based differentiation of AL and ATTR cardiac amyloidosis.

Objectives: This study was devised to describe the different cardiac magnetic resonance (CMR) appearances in light chain amyloid (AL) and transthyretin-related amyloidosis (ATTR).

Background: CMR is increasingly used to investigate patients with suspected amyloidosis. Global subendocardial late gadolinium enhancement (LGE) has been reported as typical of AL amyloidosis, whereas different patterns have been noted in ATTR amyloidosis.

Retinal microangiopathy as an initial manifestation of familial amyloid cardiomyopathy associated with transthyretin e89k mutation.

Purpose: To report a rare case of transthyretin (TTR) familial amyloid cardiomyopathy with retinal microangiopathy and vitreous amyloid as the initial manifestation.

Methods: A 54-year-old woman presented with bilateral retinal microangiopathy, presumed idiopathic retinal vasculitis. She subsequently developed retinal ischemia associated vitreous hemorrhage and was treated with panretinal laser photocoagulation.

Senile systemic amyloidosis: clinical features at presentation and outcome.

Background: Cardiac amyloidosis is a fatal disease whose prognosis and treatment rely on identification of the amyloid type. In our aging population transthyretin amyloidosis (ATTRwt) is common and must be differentiated from other amyloid types. We report the clinical presentation, natural history, and prognostic features of ATTRwt compared with cardiac-isolated AL amyloidosis and calculate the probability of disease diagnosis of ATTRwt from baseline factors.

Systemic amyloidosis in England: an epidemiological study.

Epidemiological studies of systemic amyloidosis are scarce and the burden of disease in England has not previously been estimated. In 1999, the National Health Service commissioned the National Amyloidosis Centre (NAC) to provide a national clinical service for all patients with amyloidosis. Data for all individuals referred to the NAC is held on a comprehensive central database, and these were compared with English death certificate data for amyloidosis from 2000 to 2008, obtained from the Office of National Statistics.

Inflammatory bowel disease and systemic AA amyloidosis.

Background: Systemic AA amyloidosis is a recognised complication of inflammatory bowel disease. AA amyloidosis is a potential cause of end-stage renal failure and mortality but little is known of the natural history of this condition in inflammatory bowel disease.

Methods: We evaluated the clinical phenotype, disease progression and outcome amongst 26 patients with inflammatory bowel disease and AA amyloidosis followed prospectively at a single center between 1989 and 2010.

Quantification of myocardial extracellular volume fraction in systemic AL amyloidosis: an equilibrium contrast cardiovascular magnetic resonance study.

Background: Cardiac involvement predicts outcome in systemic AL amyloidosis and influences therapeutic options. Current methods of cardiac assessment do not quantify myocardial amyloid burden. We used equilibrium contrast cardiovascular magnetic resonance (EQ-CMR) to quantify the cardiac interstitial compartment, measured as myocardial extracellular volume (ECV) fraction, hypothesizing it would reflect amyloid burden.

A prospective study of nutritional status in immunoglobulin light chain amyloidosis.

Weight loss is common in systemic immunoglobulin light chain amyloidosis but there are limited data on the impact of nutritional status on outcome. Using the Patient-Generated Subjective Global Assessment (PG-SGA) score, we prospectively examined nutritional status in 110 consecutive newly-diagnosed, treatment-naïve patients with immunoglobulin light chain amyloidosis attending the UK National Amyloidosis Centre. At study entry, 72 of 110 (66%) patients had a PG-SGA score of 4 or over, indicating malnutrition requiring specialist nutritional intervention.

The electrocardiographic features associated with cardiac amyloidosis of variant transthyretin isoleucine 122 type in Afro-Caribbean patients.

Background: About 4% of African Americans possess the isoleucine 122 (V122I) variant of transthyretin, associated with cardiac amyloidosis beyond ages of 55 to 60 years. Transthyretin amyloidosis associated with variant V122I (ATTR V122I) is likely to be an important cause of heart failure in Afro-Caribbean populations, but the high prevalence of left ventricular hypertrophy (LVH) and lack of awareness of this genetic disorder pose diagnostic hurdles. We report the electrocardiographic (ECG) features of ATTR V122I in the largest clinical series to date.

Cyclophosphamide, bortezomib, and dexamethasone therapy in AL amyloidosis is associated with high clonal response rates and prolonged progression-free survival.

Bortezomib has shown great promise in the treatment of amyloid light-chain (AL) amyloidosis. We present our experience of 43 patients with AL amyloidosis who received cyclophosphamide, bortezomib, and dexamethasone (CVD) upfront or at relapse. Of these, 74% had cardiac involvement and 46% were Mayo Cardiac Stage III.

Cardiac phenotype and clinical outcome of familial amyloid polyneuropathy associated with transthyretin alanine 60 variant.

Aims: Familial amyloid polyneuropathy (FAP) is a dominantly inherited multi-system disease associated with transthyretin (TTR) mutations. Previous series have predominantly described patients with the TTR variant Val30Met (V30M), which is the most prevalent cause of FAP worldwide. Here, we report the dominant cardiac phenotype and outcome of FAP associated with TTR Thr60Ala (T60A), the most common UK variant.

Amyloidogenicity and clinical phenotype associated with five novel mutations in apolipoprotein A-I.

The phenotype of hereditary apolipoprotein A-I amyloidosis is heterogeneous with some patients developing extensive visceral amyloid deposits and end-stage renal failure as young adults and others having only laryngeal and/or skin amyloid, which may be of little clinical consequence. Clinical management and prognosis of patients with systemic amyloidosis depend entirely on correct identification of the fibril protein, such that light chain amyloidosis (AL, previously referred to as "primary"), the most frequently diagnosed type, is treated with chemotherapy, which has absolutely no role in hereditary apolipoprotein A-I amyloidosis. We report five novel apolipoprotein A-I variants, four of which were amyloidogenic and one of which was incidental in a patient with systemic AL amyloidosis.

Outcome in renal Al amyloidosis after chemotherapy.

Purpose: Chemotherapy in AL (primary or light chain) amyloidosis is associated with improved survival, but its effect on renal outcome has not been examined systematically. The purpose of this study was to evaluate the effect of chemotherapy on clinical outcome among patients with renal AL amyloidosis.

Patients And Methods: We evaluated factors influencing survival among 923 patients with renal AL amyloidosis observed during a 21-year period, including 221 patients who became dialysis dependent.

Biochemical basis of the amyloid diseases.

Amyloidosis is a heterogeneous group of diseases characterized by normally soluble proteins deposited extracellularly in an abnormally folded, insoluble fibrillar form. This can lead to organ impairment and premature death. This article discusses the pathogenesis, classification system and means of diagnosis of the amyloid diseases.