Wild-type transthyretin cardiac amyloidosis: When is a rare disease no longer a rare disease?

In this issue of JNC, Cuscaden and colleagues report the prevalence of cardiac uptake (a hallmark of cardiac amyloidosis) in patients undergoing routine {99m}^Tc-HMDP (hydroxymethylene diphosphonate) and {99m}^Tc-MDP (methylene diphosphonate) scintigraphy, suggesting a high prevalence of the disease increasing with age.

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. Amyloidosis was stated on death certificates of 2543 individuals, representing 0·58/1000 recorded deaths. During the same period, 1143 amyloidosis patients followed at the NAC died, 903 (79%) of whom had amyloidosis recorded on their death certificates. The estimated minimum incidence of systemic amyloidosis in the English population in 2008, based on new referrals to the NAC, was 0·4/100 000 population. The incidence peaked at age 60-79 years. Systemic AL amyloidosis was the most common type with an estimated minimum incidence of 0·3/100 000 population. Although there are various limitations to this study, the available data suggest the incidence of systemic amyloidosis in England exceeds 0·8/100 000 of the population

Extracardiac 18F-florbetapir imaging in patients with systemic amyloidosis: more than hearts and minds

PURPOSE: 18F-Florbetapir has been reported to show cardiac uptake in patients with systemic light-chain amyloidosis (AL). This study systematically assessed uptake of 18F-florbetapir in patients with proven systemic amyloidosis at sites outside the heart. METHODS: Seventeen patients with proven cardiac amyloidosis underwent 18F-florbetapir PET/CT imaging, 15 with AL and 2 with transthyretin amyloidosis (ATTR). Three patients had repeat scans. All patients had protocolized assessment at the UK National Amyloidosis Centre including imaging with 123I-serum amyloid P component (SAP). 18F-Florbetapir images were assessed for areas of increased tracer accumulation and time-uptake curves in terms of standardized uptake values (SUVmean) were produced. RESULTS: All 17 patients showed 18F-florbetapir uptake at one or more extracardiac sites. Uptake was seen in the spleen in 6 patients (35%; 6 of 9, 67%, with splenic involvement on 123I-SAP scintigraphy), in the fat in 11 (65%), in the tongue in 8 (47%), in the parotids in 8 (47%), in the masticatory muscles in 7 (41%), in the lungs in 3 (18%), and in the kidney in 2 (12%) on the late half-body images. The 18F-florbetapir spleen retention index (SRI) was calculated. SRI >0.045 had 100% sensitivity/sensitivity (in relation to 123I-SAP splenic uptake, the current standard) in detecting splenic amyloid on dynamic imaging and a sensitivity of 66.7% and a specificity of 100% on the late half-body images. Intense lung uptake was seen in three patients, one of whom had lung interstitial infiltration suggestive of amyloid deposition on previous high-resolution CT. Repeat imaging showed a stable appearance in all three patients suggesting no early impact of treatment response. CONCLUSION: 18F-Florbetapir PET/CT is a promising tool for the detection of extracardiac sites of amyloid deposition. The combination of uptake in the heart and uptake in the spleen on 18F-florbetapir PET/CT, a hallmark of AL, suggests that this tracer holds promise as a screening tool for AL

Systemic Amyloidosis due to Low-Grade Lymphoma

Lymphoma-related amyloidosis is a rare entity. Systemic AL amyloidosis is generally caused by an underlying plasma cell clone in the bone marrow with an intact monoclonal immunoglobulin G (IgG) or IgA protein. The rarity of the lymphoma-related amyloidosis makes the generation of data in randomized trials and the determination of the optimal treatment almost impossible. Therefore, treatment recommendations discussed here are based on either retrospective or small prospective trials of single centers

AL Amyloidosis for Cardiologists: Awareness, Diagnosis, and Future Prospects: JACC: CardioOncology State-of-the-Art Review

Amyloid light chain (AL) amyloidosis is a rare, debilitating, often fatal disease. Symptoms of cardiomyopathy are common presenting features, and patients often are referred to cardiologists. Cardiac amyloid infiltration is the leading predictor of death. However, the variable presentation and perceived rarity of the disease frequently lead to delay in suspecting amyloidosis as a cause of heart failure, leading to misdiagnoses and a marked delay in diagnosis, with devastating consequences for the patient. A median time from symptom onset to correct diagnosis of about 2 years is often too long when median survival from diagnosis for patients with AL amyloidosis and cardiomyopathy is 4 months to 2 years. The authors highlight the challenges to diagnosis, identify gaps in the current knowledge, and summarize novel treatments on the horizon to raise awareness about the critical need for early recognition of symptoms and diagnosis of AL amyloidosis aimed at accelerating treatment and improving outcomes for patients

Diagnosis, pathogenesis and outcome in leucocyte chemotactic factor 2 (ALECT2) amyloidosis

Introduction: Renal biopsy series from North America suggest that leucocyte chemotactic factor 2 (ALECT2) amyloid is the third most common type of renal amyloid. We report the first case series from a European Centre of prevalence, clinical presentation and diagnostic findings in ALECT2 amyloidosis and report long-term patient and renal outcomes for the first time. Methods: We studied the clinical features, diagnostic investigations and the outcome of all patients with ALECT2 amyloidosis followed systematically at the UK National Amyloidosis Centre (NAC) between 1994 and 2015. Results: Twenty-four patients, all non-Caucasian, were diagnosed with ALECT2 amyloidosis representing 1.3% of all patients referred to the NAC with biopsy-proved renal amyloid. Diagnosis was made at median age of 62 years, usually from renal histology; immunohistochemical staining was definitive for ALECT2 fibril type. Median estimated glomerular filtration rate (GFR) at diagnosis was 33 mL/min/1.73 m2 and median proteinuria was 0.5 g/24 h. Hepatic amyloid was evident on serum amyloid P component (SAP) scintigraphy in 11/24 cases but was not associated with significant derangement of liver function. No patient had evidence of cardiac amyloidosis or amyloid neuropathy. Median follow-up was 4.8 (range 0.5–15.2) years, during which four patients died and four progressed to end-stage renal disease. The mean rate of GFR loss was 4.2 (range 0.5–9.6) mL/min/year and median estimated renal survival from diagnosis was 8.2 years. Serial SAP scans revealed little or no change in total body amyloid burden. Conclusions: ALECT2 amyloidosis is a relatively benign type of renal amyloid, associated with a slow GFR decline, which is reliably diagnosed on renal histology. Neither the molecular basis nor the factors underlying the apparent restriction of ALECT2 amyloidosis to non-Caucasian populations have been determined

Diagnostic sensitivity of abdominal fat aspiration in cardiac amyloidosis

Aims: Congo red staining of an endomyocardial biopsy is the diagnostic gold-standard in suspected cardiac amyloidosis (CA), but the procedure is associated with the risk, albeit small, of serious complications, and delay in diagnosis due to the requirement for technical expertise. In contrast, abdominal fat pad fine needle aspiration (FPFNA) is a simple, safe and well-established procedure in systemic amyloidosis, but its diagnostic sensitivity in patients with suspected CA remains unclear. Methods and results: We assessed the diagnostic sensitivity of FPFNA in 600 consecutive patients diagnosed with CA [216 AL amyloidosis, 113 hereditary transthyretin (ATTRm), and 271 wild-type transthyretin (ATTRwt) amyloidosis] at our Centre. Amyloid was detected on Congo red staining of FPFNAs in 181/216 (84%) patients with cardiac AL amyloidosis, including 100, 97, and 78% of those with a large, moderate, and small whole-body amyloid burden, respectively, as assessed by serum amyloid P (SAP) component scintigraphy (P < 0.001); the deposits were successfully typed as AL by immunohistochemistry in 102/216 (47%) cases. Amyloid was detected in FPFNAs of 51/113 (45%) patients with ATTRm CA, and only 42/271 (15%) cases with ATTRwt CA. Conclusions: FPFNA has reasonable diagnostic sensitivity in cardiac AL amyloidosis, particularly in patients with a large whole-body amyloid burden. Although the diagnostic sensitivity of FPFNA is substantially lower in transthyretin CA, particularly ATTRwt, it may nevertheless sometimes obviate the need for endomyocardial biopsy