BackgroundCardiac 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.Methods and ResultsAll patients with biopsy‐proven ATTRwt (102 cases) and isolated cardiac AL (36 cases) seen from 2002 to 2011 at the UK National Amyloidosis Center were included. Median survival from the onset of symptoms was 6.07 years in the ATTRwt group and 1.7 years in the AL group. Positive troponin, a pacemaker, and increasing New York Heart Association (NYHA) class were associated with worse survival in ATTRwt patients on univariate analysis. All patients with isolated cardiac AL and 24.1% of patients with ATTRwt had evidence of a plasma cell dyscrasia. Older age and lower N‐terminal pro‐B‐type natriuretic peptide (NT pro‐BNP) were factors significantly associated with ATTRwt. Patients aged 70 years and younger with an NT pro‐BNP <183 pmol/L were more likely to have ATTRwt, as were patients older than 70 years with an NT pro‐BNP <1420 pmol/L.ConclusionsFactors at baseline associated with a worse outcome in ATTRwt are positive troponin T, a pacemaker, and NYHA class IV symptoms. The age of the patient at diagnosis and NT pro‐BNP level can aid in distinguishing ATTRwt from AL amyloidosis.

Transmural patterns of LGE distinguished ATTR from AL cardiac amyloidosis with high accuracy in this real-world analysis of CMR. Precise diagnosis of cardiac amyloidosis is crucial given the role of chemotherapy in AL type and with novel therapies for ATTR type currently in development.

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. Methods and Results— Sixty patients with systemic AL amyloidosis (65% men, median age 65 years) underwent conventional clinical cardiovascular magnetic resonance, including late enhancement, equilibrium contrast cardiovascular magnetic resonance, and clinical cardiac evaluation, including ECG, echocardiography, assays of N-terminal pro-brain natriuretic peptide and Troponin T, and functional assessment comprising the 6-minute walk test in ambulant individuals. Cardiac involvement in the amyloidosis patients was categorized as definite, probable, or none, suspected by conventional criteria. Findings were compared with 82 healthy controls. Mean ECV was significantly greater in patients than healthy controls (0.25 versus 0.40, P <0.001) and correlated with conventional criteria for characterizing the presence of cardiac involvement, the categories of none, probable, definite corresponding to ECV of 0.276 versus 0.342 versus 0.488, respectively ( P <0.001). ECV was correlated with cardiac parameters by echocardiography (eg, Tissue Doppler Imaging [TDI] S-wave R=0.52, P<0.001) and conventional cardiovascular magnetic resonance (eg, indexed left ventricular mass R =0.56, P <0.001). There were also significant correlations with N-terminal pro-brain natriuretic peptide ( R =0.69, P <0.001) and Troponin T ( R =0.53, P =0.006). ECV was associated with smaller QRS voltages ( R =0.57, P <0.001) and correlated with poorer performance in the 6-minute walk test ( R =0.36, P =0.03). Conclusions— Myocardial ECV measurement has potential to become the first noninvasive test to quantify cardiac amyloid burden.

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.

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. The overall hematologic response rate was 81.4%, including complete response (CR) in 41.9% and very good partial response with > 90% decrease in difference between involved/ uninvolved light chain (VGPR-dFLC) in 51.4%. Patients treated upfront had higher rates of CR (65.0%) and VGPR-dFLC (66.7%). The estimated 2-year progressionfree survival was 66.5% for patients treated upfront and 41.4% for relapsed patients. Those attaining a CR or VGPR-dFLC had a significantly better progression-free survival (P ‫؍‬ .002 and P ‫؍‬ .026, respectively IntroductionBortezomib has been shown to be effective in the treatment of amyloid light-chain (AL) amyloidosis. [1][2][3][4][5][6][7][8] Although the efficacy of proteosome inhibitors is based several different mechanisms, of particular relevance to AL amyloidosis is "proteostasis" because of both the excess light-chain production and accumulation of the misfolded proteins. 9,10 Based on the success of bortezomib in myeloma treatment regimens, initial retrospective series showing efficacy with bortezomib with or without dexamethasone 1,7,11 in AL amyloidosis have laid the groundwork for recent prospective clinical trials showing high response rates but have also raised questions about response durability. 4,5 Given the excellent outcomes in myeloma using a steroid/ alkylator backbone in combination with bortezomib, 12,13 similar strategies have been explored in AL amyloidosis. 3,8 In the present study, we describe our experience with the combination of bortezomib, cyclophosphamide, and dexamethasone (CVD) in patients with AL amyloidosis treated in both the upfront and relapsed setting, reporting response and progression-free survival (PFS). Study designThe primary cohort is a retrospective series of 43 patients from the National Amyloidosis Center in London from January 2006 to March 2011 who underwent detailed prospective evaluation as per standard protocol. The median age of these patients was 54 years and 58% were male. Organ involvement and hematologic and organ responses were defined according to international amyloidosis consensus criteria from 2005 14 and were as follows: cardiac, 74%; renal, 79%; liver, 23%; peripheral neuropathy, 18%; autonomic neuropathy, 21%; and other organs, 35%. Complete information for staging by the Mayo Clinic criteria 15 was available in 39 patients and 46% were stage III based on values obtained before the initiation of CVD (22% of upfront patients and 62% of relapsed patients). The CVD regimen was as follows: bortezomib 1.0 mg/m 2 IV on days 1, 4, 8, 11 (increased to 1.3 mg/m 2 if well tolerated); cyclophosphamide 350 mg/m 2 orally on days 1, 8, and 15; and dexamethasone 20 mg orally on days 1, 4, 8, and 11 (increased to 20 mg f...

Background and objectives: N-terminal probrain type natriuretic peptide (NTproBNP) has been proven to be a valuable biomarker for predicting cardiac events and mortality in the hemodialysis population. However recent reports have suggested that NTproBNP is a marker of volume overload rather than one of cardiac dysfunction. Therefore this study investigated the effect of fluid volume status on NTproBNP.Design, setting, participants, & measurements: Volume status was determined pre-and postdialysis in 72 stable hemodialysis outpatients by multifrequency bioimpedance, and the relationship to NTproBNP values was examined.Results: The mean and median NTproBNP values were 931.9 ؎ 230 and 242 (90 to 688) pmol/L, respectively. On simple correlation, NTproBNP was associated with markers of volume overload and cardiac dysfunction. However, on logistical regression analysis, the strongest association was with the predialysis ratio of extracellular water/total body water (␤ 26.6, F29.6, P ‫؍‬ 0.000), followed by postdialysis mean arterial blood pressure (␤ 0.14, F17.1, P ‫؍‬ 0.000), dialysate calcium concentration (␤ ؊1.19, F14.1, P ‫؍‬ 0.002), and change in extracellular fluid volume with dialysis (␤ 0.27, F7.4, P ‫؍‬ 0.009) Conclusions: In this study, NTproBNP was not associated with cardiac dysfunction as assessed by transthoracic echo or nuclear medicine scintigraphy but was dependent on factors associated with volume overload. However, because bioimpedance results can also be affected by malnutrition with loss of cell mass, NTproBNP may be elevated not only in patients with volume overload, but also those with malnutrition.

Cardiac amyloidosis is almost always present at diagnosis in FAP T60A, and is a major determinant of its poor prognosis. Outcome of liver transplantation in FAP T60A has been discouraging.

A B S T R A C T PurposeChemotherapy 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 MethodsWe evaluated factors influencing survival among 923 patients with renal AL amyloidosis observed during a 21-year period, including 221 patients who became dialysis dependent. Factors associated with renal outcome were analyzed, including serum free light chain (FLC) response to chemotherapy using a simple subtraction formula applicable to all stages of chronic kidney disease. Patient survival and graft survival were analyzed in 21 renal transplantation recipients. ResultsMedian survival from diagnosis for the whole cohort was 35.2 months. Magnitude of FLC response with chemotherapy was strongly and independently associated with overall survival (P Ͻ .001) and renal outcome. Evaluable patients achieving more than 90% FLC response had a significantly higher rate of renal responses and lower rate of renal progression compared with patients achieving a 50% to 90% response, whose renal outcomes were, in turn, better than patients achieving less than 50% FLC response (P Ͻ .001). Median survival from dialysis dependence was 39.0 months, and median survival from renal transplantation was 89.0 months. ConclusionRenal outcome and overall outcome in AL amyloidosis are strongly associated with FLC response to chemotherapy and are best among patients achieving more than 90% suppression of the amyloidogenic monoclonal component. Survival on dialysis was substantially superior to that previously reported, and renal transplantation should be considered in selected patients with AL amyloidosis with end-stage renal disease.J Clin Oncol 29:674-681.