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Búsqueda Bibliográfica: Amiloidosis (2005-2012)
1. Amyloid. 2013 Dec;20(4):212-20. doi: 10.3109/13506129.2013.825240. Epub 2013 Aug 21.
Role of natriuretic peptide to predict cardiac abnormalities in patients withhereditary transthyretin amyloidosis.
Damy T(1), Deux JF, Moutereau S, Guendouz S, Mohty D, Rappeneau S, Guellich A,Hittinger L, Loric S, Lefaucheur JP, Plante-Bordeneuve V.
Author information: (1)Department of cardiology .
BACKGROUND: Familial amyloid polyneuropathy (FAP) mainly targets the peripheralnervous system and heart. Early noninvasive detection of cardiac impairment iscritical for therapeutic management.AIM: To assess if amino-terminal pro-brain natriuretic peptide (NT-proBNP) ortroponin T (cTnT) can predict echocardiographic left-ventricle (LV) impairment inFAP.METHODS: Thirty-six asymptomatic carriers and patients with FAP hadechocardiographic measurement of left-ventricular (LV) systolic function,hypertrophy (LVH) and estimation of filling pressure (FP).RESULTS: Overall, median age, NT-proBNP, and LV ejection fraction were,respectively, 59 years (41-74), 323 pg/ml (58-1960), and 60% (51-66). Twelvepatients had increased cTnT. Prevalence of ATTR gene mutations was 53% forVal30Met. Four individuals were asymptomatic, 6 patients had isolatedneurological clinical signs, and 26 had echo-LV abnormalities. The ROC curveidentified NT-proBNP patients with echo-LV abnormalities (area: 0.92;(0.83-0.99), p = 0.001) at a threshold >82 pg/ml with a sensitivity of 92%, and aspecificity of 90%. Increased in NT-proBNP occurred in patients with SD and/orLVH with or without increase in FP. Elevated cTnT (>0.01 ng/ml) was only observedin patients with LVH and systolic dysfunction, with or without FP.CONCLUSION: In FAP, NT-proBNP was associated with cardiac impairment suggestingthat NT-proBNP could be used in carriers or in FAP patients with only neurologic symptoms for identifying the appropriate time to start cardiac echocardiographic assessment and follow-up. cTnT identified patients with severe cardiac disease.
PMID: 23964755 [PubMed - indexed for MEDLINE]
2. Am J Hematol. 2013 May;88(5):416-25. doi: 10.1002/ajh.23400.
Immunoglobulin light chain amyloidosis: 2013 update on diagnosis, prognosis, and treatment.
Author information: Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA.firstname.lastname@example.org
DISEASE OVERVIEW: Immunoglobulin (Ig) light chain amyloidosis is a clonal,nonproliferative plasma cell disorder in which fragments of Ig light chain aredeposited in tissues. Clinical features depend on organs involved but can includerestrictive cardiomyopathy, nephrotic syndrome, hepatic failure,peripheral/autonomic neuropathy, and atypical multiple myeloma.DIAGNOSIS: Tissue biopsy stained with Congo red demonstrating amyloid depositswith apple-green birefringence is required for diagnosis. Invasive organ biopsyis not required because amyloid deposits can be found in bone marrow biopsy orsubcutaneous fat aspirate in 85% of patients. Verification that amyloid is ofimmunoglobulin origin is mandatory.PROGNOSIS: N-terminal pro-brain natriuretic peptide (NT-proBNP), serum troponinT, and immunoglobulin free light chain values are used to classify patients into four groups of similar size; median survivals are 94.1, 40.3, 14.0, and 5.8months.THERAPY: All patients with a visceral amyloid syndrome require therapy to preventdeposition of amyloid in other viscera and prevent progressive organ failure ofinvolved sites. Stem cell transplant (SCT) is preferred, but only 20% of patientsare eligible. Requirements for safe SCT include NT-proBNP <5,000 ng/mL, troponin T < 0.06 ng/mL, age <70 years, <3 organs involved, and serum creatinine ≤1.7mg/dL. Nontransplant candidates can be offered melphalan-dexamethasone.Pomalidomide appears to have activity, as do other combinations of chemotherapywith agents such as cyclophosphamide-thalidomide (or lenalidomide orbortezomib)-dexamethasone, bortezomib-dexamethasone, andmelphalan-prednisone-lenalidomide.FUTURE CHALLENGES: Late diagnosis remains a major obstacle to initiatingeffective therapy when organ dysfunction is still recoverable. Recognizing thepresenting syndromes is necessary for improving survival.
Copyright © 2013 Wiley Periodicals, Inc.
PMID: 23605846 [PubMed - indexed for MEDLINE]
3. J Clin Oncol. 2012 Dec 20;30(36):4541-9. doi: 10.1200/JCO.2011.37.7614. Epub 2012Oct 22.
New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: impact on survival outcomes.
Palladini G(1), Dispenzieri A, Gertz MA, Kumar S, Wechalekar A, Hawkins PN,Schönland S, Hegenbart U, Comenzo R, Kastritis E, Dimopoulos MA, Jaccard A,Klersy C, Merlini G.
Author information: (1)Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico SanMatteo Pavia, Italy.
Comment in J Clin Oncol. 2013 Jul 20;31(21):2749-50. J Clin Oncol. 2013 Jul 20;31(21):2750-1.
PURPOSE: To identify the criteria for hematologic and cardiac response totreatment in immunoglobulin light chain (AL) amyloidosis based on survivalanalysis of a large patient population.PATIENTS AND METHODS: We gathered for analysis 816 patients with AL amyloidosisfrom seven referral centers in the European Union and the United States. Adifferent cohort of 374 patients prospectively evaluated at the Pavia AmyloidosisResearch and Treatment Center was used for validation. Data was available for allpatients before and 3 and/or 6 months after initiation of first-line therapy. Theprognostic relevance of different criteria for hematologic and cardiac responsewas assessed.RESULTS: There was a strong correlation between the extent of reduction ofamyloidogenic free light chains (FLCs) and improvement in survival. This allowed the identification of four levels of response: amyloid complete response (normal FLC ratio and negative serum and urine immunofixation), very good partialresponse (difference between involved and uninvolved FLCs [dFLC] < 40 mg/L),partial response (dFLC decrease > 50%), and no response. Cardiac involvement isthe major determinant of survival, and changes in cardiac function after therapy can be reliably assessed using the cardiac biomarker N-terminal natriureticpeptide type B (NT-proBNP). Changes in FLC and NT-proBNP predicted survival asearly as 3 months after treatment initiation.CONCLUSION: This study identifies and validates new criteria for response tofirst-line treatment in AL amyloidosis, based on their association with survival in large patient populations, and offers surrogate end points for clinicaltrials.
PMID: 23091105 [PubMed - indexed for MEDLINE]
4. Am J Hematol. 2012 May;87(5):465-71. doi: 10.1002/ajh.23141. Epub 2012 Mar 3.
Best use of cardiac biomarkers in patients with AL amyloidosis and renal failure.
Palladini G(1), Foli A, Milani P, Russo P, Albertini R, Lavatelli F, Obici L,Perlini S, Moratti R, Merlini G.
Author information: (1)Amyloidosis Research and Treatment Center, Biotechnology ResearchLaboratories-Department of Molecular Medicine, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo Pavia, Italy.
In AL amyloidosis prognosis depends on the severity of heart dysfunction which isbest assessed by natriuretic peptides (BNP and NT-proBNP). However, theirclearance relies on glomerular filtration rate (GFR) and their concentrationincreases with renal failure. We evaluated the diagnostic and prognosticperformance of NT-proBNP and BNP in 248 patients with AL amyloidosis withdifferent degrees of renal failure. Patients were grouped according to GFR. Group1 comprised 109 patients with GFR ≥60 mL/min/1.73 m(2) , Group 2, 77 subjectswith GFR <60 and ≥15 mL/min/1.73 m(2) , and Group 3, 62 patients with GFR <15mL/min/1.73 m(2) . The ability of natriuretic peptides to detect heartinvolvement and to predict survival in the three groups was assessed. Decreasing eGFR required higher cutoffs of both NT-proBNP and BNP for detecting heartinvolvement and predicting survival. Both natriuretic peptides were independentprognostic markers in Groups 1 and 2, whereas in Group 3 only BNP independentlypredicted survival. Natriuretic peptides are powerful and useful markers ofcardiac dysfunction and prognosis, provided that eGFR is considered ininterpreting their clinical meaning. BNP should be preferred in patients withend-stage renal failure.
Copyright © 2012 Wiley Periodicals, Inc.
PMID: 22389105 [PubMed - indexed for MEDLINE]
5. J Clin Oncol. 2012 Mar 20;30(9):989-95. doi: 10.1200/JCO.2011.38.5724. Epub 2012 Feb 13.
Revised prognostic staging system for light chain amyloidosis incorporatingcardiac biomarkers and serum free light chain measurements.
Kumar S(1), Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Colby C, Laumann K,Zeldenrust SR, Leung N, Dingli D, Greipp PR, Lust JA, Russell SJ, Kyle RA,Rajkumar SV, Gertz MA.
Author information: (1)Mayo Clinic, Rochester, MN, USA. email@example.com
PURPOSE: Cardiac involvement predicts poor prognosis in light chain (AL)amyloidosis, and the current prognostic classification is based on cardiacbiomarkers troponin-T (cTnT) and N-terminal pro-B-type natriuretic peptide(NT-ProBNP). However, long-term outcome is dependent on the underlying plasmacell clone, and incorporation of clonal characteristics may allow for better riskstratification.PATIENTS AND METHODS: We developed a prognostic model based on 810 patients with newly diagnosed AL amyloidosis, which was further examined in two other datasets:303 patients undergoing stem-cell transplantation, and 103 patients enrolled ontodifferent clinical trials.RESULTS: We examined the prognostic value of plasma cell-related characteristics (ie, difference between involved and uninvolved light chain [FLC-diff], marrowplasma cell percentage, circulating plasma cells, plasma cell labeling index, andβ(2) microglobulin). In a multivariate model that included these characteristics as well as cTnT and NT-ProBNP, only FLC-diff, cTnT, and NT-ProBNP wereindependently prognostic for overall survival (OS). Patients were assigned ascore of 1 for each of FLC-diff ≥ 18 mg/dL, cTnT ≥ 0.025 ng/mL, and NT-ProBNP ≥1,800 pg/mL, creating stages I to IV with scores of 0 to 3 points, respectively. The proportions of patients with stages I, II, III and IV disease were 189 (25%),206 (27%), 186 (25%) and 177 (23%), and their median OS from diagnosis was 94.1, 40.3, 14, and 5.8 months, respectively (P < .001). This classification system wasvalidated in the other datasets.CONCLUSION: Incorporation of serum FLC-diff into the current staging systemimproves risk stratification for patients with AL amyloidosis and will helpdevelop risk-adapted therapies for AL amyloidosis.
PMCID: PMC3675680PMID: 22331953 [PubMed - indexed for MEDLINE]
6. Amyloid. 2011 Jun;18 Suppl 1:96-7. doi: 10.3109/13506129.2011.574354035.
Functional correlates of N-terminal natriuretic peptide type B (NT-proBNP)response to therapy in cardiac light chain (AL) amyloidosis.
Perlini S(1), Musca F, Salinaro F, Fracchioni I, Palladini G, Obici L, Albertini R, Moratti R, Lavatelli F, Palladini G, Rapezzi C, Merlini G.
Author information: (1)Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo andUniversity of Pavia, Italy. firstname.lastname@example.org
Erratum in Amyloid. 2011 Jun;18 Suppl 1:97.
PMID: 21838447 [PubMed - indexed for MEDLINE]
7. Blood. 2010 Nov 4;116(18):3426-30. doi: 10.1182/blood-2010-05-286567. Epub 2010Jul 19.
The combination of high-sensitivity cardiac troponin T (hs-cTnT) at presentation and changes in N-terminal natriuretic peptide type B (NT-proBNP) afterchemotherapy best predicts survival in AL amyloidosis.
Palladini G(1), Barassi A, Klersy C, Pacciolla R, Milani P, Sarais G, Perlini S, Albertini R, Russo P, Foli A, Bragotti LZ, Obici L, Moratti R, Melzi d'Eril GV,Merlini G.
Author information: (1)Amyloidosis Research and Treatment Center and Department of Biochemistry,Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS)Policlinico San Matteo and University of Pavia, Viale Golgi 19, Pavia, Italy.
In light-chain (AL) amyloidosis, prognosis is dictated by cardiac dysfunction.N-terminal natriuretic peptide type B (NT-proBNP) and cardiac troponins (cTn) areused to assess the severity of cardiac damage. We evaluated the prognosticrelevance of a high-sensitivity (hs) cTnT assay, NT-proBNP, and cardiac troponin I in 171 consecutive patients with AL amyloidosis at presentation and 6 monthsafter treatment. Response and progression of NT-proBNP were defined as more than 30% and more than 300 ng/L changes. All 3 markers predicted survival, but thebest multivariable model included hs-cTnT. The hs-cTnT prognostic cutoff was 77ng/L (median survival 10.6 months for patients with hs-cTnT above the cutoff).After treatment, response and progression of NT-proBNP and a more than 75%increase of hs-cTnT were independent prognostic determinant. In AL amyloidosis,hs-cTnT is the best baseline prognostic marker. Therapy should be aimed atpreventing progression of cardiac biomarkers, whereas NT-proBNP response confers an additional survival benefit.
PMID: 20644111 [PubMed - indexed for MEDLINE]
8. Amyloid. 2009 Dec;16(4):187-95. doi: 10.3109/13506120903421538.
Serum levels of NT-proBNP as surrogate for cardiac amyloid burden: new evidencefrom gadolinium-enhanced cardiac magnetic resonance imaging in patients withamyloidosis.
Lehrke S(1), Steen H, Kristen AV, Merten C, Lossnitzer D, Dengler TJ, Katus HA,Giannitsis E.
Author information: (1)Department of Medicine III, Division of Cardiology, University HospitalHeidelberg, Heidelberg, Germany. email@example.com
BACKGROUND: The prognostic value of NT-proBNP has been recognized in patientswith amyloidosis complicated by cardiac involvement. We aimed to use contrastenhanced cardiac magnetic resonance imaging (CMR) to identify functional andstructural alterations related to levels of NT-proBNP better to understand themechanisms of its release in cardiac amyloidosis.METHODS AND RESULTS: CMR was performed on a 1.5-T scanner in 34 patients withbiopsy proven amyloid light chain (AL; n = 27) or hereditary transthyretinrelated (TTR; n = 7) amyloidosis. NT-proBNP was higher in patients with (n = 25) compared to patients without cardiac involvement (n = 9) (2931 (IQR: 972-8629;min-max: 25-27,277) pg/ml vs. 177 (IQR: 71-1431; min-max: 22-7935) pg/ml, p =0.008). ROC analysis identified a NT-proBNP of <2426.5 pg/ml as optimaldiscriminator for event free survival (682 +/- 65 days). NT-proBNP did notcorrelate with LV- ejection fraction, end-diastolic and end-systolic volumes orstroke volume. There was a moderate correlation between NT-proBNP and LV-mass (R = 0.52, p = 0.003) and extent of late gadolinium enhancement (LGE; R = 0.41, p = 0.04).CONCLUSIONS: This study confirms the prognostic value of NT-proBNP in patientswith AL and TTR amyloidosis and provides the novel finding that NT-proBNPcorrelates with surrogates of myocardial amyloid burden such as LV-mass and LGE, supporting the concept of NT-proBNP as a biomarker reflecting the severity ofcardiac amyloid infiltration.
PMID: 19922329 [PubMed - indexed for MEDLINE]
9. J Clin Oncol. 2004 Sep 15;22(18):3751-7.
Serum cardiac troponins and N-terminal pro-brain natriuretic peptide: a stagingsystem for primary systemic amyloidosis.
Dispenzieri A(1), Gertz MA, Kyle RA, Lacy MQ, Burritt MF, Therneau TM, Greipp PR,Witzig TE, Lust JA, Rajkumar SV, Fonseca R, Zeldenrust SR, McGregor CG, Jaffe AS.
Author information: (1)Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN 55905,USA. firstname.lastname@example.org
PURPOSE: Primary systemic amyloidosis (AL) is a multisystemic disorder resulting from an underlying plasma cell dyscrasia. There is no formal staging system forAL, making comparisons between studies and treatment centers difficult. Our grouppreviously identified elevated serum cardiac troponin T (cTnT) as the mostpowerful predictor of overall survival. Others have reported that N-terminalpro-brain natriuretic peptide (NT-proBNP) is a valuable prognostic marker. Wesought to develop a staging system for patients with AL.PATIENTS AND METHODS: Two hundred forty-two patients with newly diagnosed AL who were seen at the Mayo Clinic between April 1979 and November 2000, and who hadechocardiograms and stored serum samples at presentation were eligible for thisretrospective review. NT-proBNP measurements were performed on 242 patients inwhom cTnT and cardiac troponin I (cTnI) had been previously run. Two prognosticmodels were designed using threshold values of NT-proBNP and either cTnT or cTnI (NT-proBNP < 332 ng/L, cTnT < 0.035 microg/L, and cTnI < 0.1 microg/L). Dependingon whether NT-proBNP and troponin levels were both low, were high for only onelevel, or were both high, patients were classified as stage I, II, or III,respectively.RESULTS: Using the cTnT+NT-proBNP model 33%, 30%, and 37% of patients were stagesI, II, and III, respectively, with median survivals of 26.4, 10.5, and 3.5months, respectively. The alternate cTnI+NT-proBNP model predicted mediansurvivals of 27.2, 11.1, and 4.1 months, respectively.CONCLUSION: Stratification of AL patients into three stages is possible with two readily available and reproducible tests setting the stage for more consistentand reliable cross comparisons of therapeutic outcomes.
PMID: 15365071 [PubMed - indexed for MEDLINE]
10. Blood. 2004 Sep 15;104(6):1881-7. Epub 2004 Mar 25.
Prognostication of survival using cardiac troponins and N-terminal pro-brainnatriuretic peptide in patients with primary systemic amyloidosis undergoingperipheral blood stem cell transplantation.
Dispenzieri A(1), Gertz MA, Kyle RA, Lacy MQ, Burritt MF, Therneau TM, McConnell JP, Litzow MR, Gastineau DA, Tefferi A, Inwards DJ, Micallef IN, Ansell SM,Porrata LF, Elliott MA, Hogan WJ, Rajkumar SV, Fonseca R, Greipp PR, Witzig TE,Lust JA, Zeldenrust SR, Snow DS, Hayman SR, McGregor CG, Jaffe AS.
Author information: (1)Division of Hematology and Internal Medicine, Mayo Clinic, 200 First Street SW,Rochester, MN 55905, USA. email@example.com
Primary systemic amyloidosis (AL) is a fatal plasma cell disorder. Pilot datasuggest survival is better in patients undergoing peripheral blood stem celltransplantation (PBSCT), but the selection process makes the apparent benefitsuspect. We have reported that circulating cardiac biomarkers are the bestpredictors of survival outside of the transplantation setting. We now testwhether cardiac troponins (cTnT and cTnI) and N-terminal pro-brain natriureticpeptide (NT-proBNP) are prognostic in transplant recipients. In 98 patients with AL undergoing PBSCT, serum cardiac biomarkers were measured (cTnT, 98 patients;cTnI, 65 patients; and NT-proBNP, 63 patients). Elevated levels of cTnT, cTnI,and NT-proBNP were present in 14%, 43%, and 48% of patients, respectively. At 20 months median follow-up, median survival has not been reached for patients withvalues below the thresholds; in patients with values above the thresholds, mediansurvival is 26.1 months, 66.1 months, and 66.1 months, respectively. Ourpreviously reported risk systems incorporating these markers were alsoprognostic, notably the cTnT/NT-proBNP staging. Using this system, 49%, 38%, and 13% of patients were in stage I, stage II, and stage III, respectively.Determining levels of circulating biomarkers may be the most powerful tool forstaging patients with AL undergoing PBSCT.
PMID: 15044258 [PubMed - indexed for MEDLINE]
11. Circulation. 2003 May 20;107(19):2440-5. Epub 2003 Apr 28.
Serum N-terminal pro-brain natriuretic peptide is a sensitive marker ofmyocardial dysfunction in AL amyloidosis.
Palladini G(1), Campana C, Klersy C, Balduini A, Vadacca G, Perfetti V, PerliniS, Obici L, Ascari E, d'Eril GM, Moratti R, Merlini G.
Author information: (1)Department of Internal Medicine, University Hospital IRCCS Policlinico SanMatteo. University of Pavia, Pavia, Italy.
BACKGROUND: Brain natriuretic peptide (BNP) is a marker of ventriculardysfunction and can be used to assess prognosis in heart failure and aftermyocardial infarction. Heart involvement is the most important prognostic factor and causes death in almost all patients with light-chain amyloidosis (AL). Weinvestigated the prognostic value of NT-proBNP and its utility in monitoringamyloid heart dysfunction.METHODS AND RESULTS: NT-proBNP was quantified at diagnosis in 152 consecutivepatients seen at the coordinating center of the Italian Amyloidosis Study Group(Pavia) from 1999 throughout 2001. Heart involvement was estimated on the basisof clinical signs, electrocardiography, and echocardiography. NT-proBNPconcentrations differed in patients with (n=90, 59%) and without (n=62, 41%)heart involvement (median: 507.8 pmol/L versus 22.1 pmol/L, P=10(-7)). The bestcutoff for heart involvement was at 152 pmol/L (sensitivity: 93.33%, specificity:90.16%, accuracy: 92.05%) and distinguished two groups with different survival(P<0.001). The Cox multivariate model including NT-proBNP was better than models including echocardiographic and clinical signs of heart involvement. NT-proBNPappeared to be more sensitive than conventional echocardiographic parameters indetecting clinical improvement or worsening of amyloid cardiomyopathy duringfollow-up.CONCLUSIONS: NT-proBNP appeared to be the most sensitive index of myocardialdysfunction and the most powerful prognostic determinant in AL amyloidosis. Itadds prognostic information for newly diagnosed patients and can be useful indesigning therapeutic strategies and monitoring response. NT-proBNP is asensitive marker of heart toxicity caused by amyloidogenic light chains.
PMID: 12719281 [PubMed - indexed for MEDLINE]
12. Amyloid. 2013 Dec;20(4):251-5. doi: 10.3109/13506129.2013.844122. Epub 2013 Oct10.
Usefulness of plasma B-type natriuretic peptide as a prognostic marker of cardiacfunction in senile systemic amyloidosis and in familial amyloidoticpolyneuropathy.
Usuku H(1), Obayashi K, Shono M, Oshima T, Tasaki M, Yasuda H, Ogawa H, Ando Y.
Author information: (1)Department of Cardiovascular Medicine, Kumamoto Chuo Hospital , Kumamoto , Japan .
OBJECTIVE: In senile systemic amyloidosis (SSA), a common age-relatedamyloidosis, wild-type transthyretin accumulates in tissues, with a primaryresult being cardiac dysfunction. Here, we aimed to clarify the usefulness ofB-type natriuretic peptide (BNP) as a prognostic marker of cardiac function inSSA and in familial amyloidotic polyneuropathy (FAP).METHODS AND RESULTS: We studied 13 patients with severe SSA and 14 patients with FAP. SSA patients, but not FAP patients, demonstrated a significant correlationof log BNP with the echocardiographic diastolic marker E/e' ratio (r = 0.78, p < 0.01). SSA patients also showed significant correlations between log BNP and log C-reactive protein or log high-sensitive troponin T (r = 0.70, p < 0.01; r =0.64, p < 0.05). FAP patients, however, had significant correlations between log BNP and left ventricular wall thickness (intraventricular septum thicknessdiastole and posterior wall thickness diastole) (r = 0.73, p < 0.01; r = 0.77, p < 0.01). The mean log BNP level in the follow-up period was significantly higher than that in the diagnostic period in SSA patients (2.65 ± 0.45 versus 2.36 ±0.40, p < 0.01) but not in FAP patients (1.91 ± 0.56 versus 1.93 ± 0.45, p =0.87). An especially notable phenomenon was the high plasma BNP level (≥180pg/ml) in SSA patients.CONCLUSION: Plasma BNP levels may be a useful prognostic marker of cardiacfunction in SSA.
PMID: 24111636 [PubMed - indexed for MEDLINE]
13. FEBS Lett. 2014 Jan 3;588(1):52-7. doi: 10.1016/j.febslet.2013.10.049. Epub 2013 Nov 9.
An N-terminal pro-atrial natriuretic peptide (NT-proANP) 'aggregation-prone'segment involved in isolated atrial amyloidosis.
Louros NN(1), Iconomidou VA(1), Tsiolaki PL(1), Chrysina ED(2), Baltatzis GE(3), Patsouris ES(3), Hamodrakas SJ(4).
Author information: (1)Department of Cell Biology and Biophysics, Faculty of Biology, University ofAthens, Panepistimiopolis, Athens 157 01, Greece.(2)Institute of Biology, Medicinal Chemistry and Biotechnology, National HellenicResearch Foundation, 48 Vassileos Constantinou Avenue, Athens 116 35, Greece.(3)1st Department of Pathology, Medical School, University of Athens, 75 MikrasAssias, Goudi 115 27, Greece.(4)Department of Cell Biology and Biophysics, Faculty of Biology, University ofAthens, Panepistimiopolis, Athens 157 01, Greece. Electronic address:firstname.lastname@example.org.
Isolated atrial amyloidosis (IAA) is a common localized form of amyloiddeposition within the atria of the aging heart. The main constituents of amyloid fibrils are atrial natriuretic peptide (ANP) and the N-terminal part of itsprecursor form (NT-proANP). An 'aggregation-prone' heptapeptide((114)KLRALLT(120)) was located within the NT-proANP sequence. This peptideself-assembles into amyloid-like fibrils in vitro, as electron microscopy, X-ray fiber diffraction, ATR FT-IR spectroscopy and Congo red staining studies reveal. Consequently, remedies/drugs designed to inhibit the aggregation tendency of this'aggregation-prone' segment of NT-proANP may assist in prevention/treatment ofIAA, congestive heart failure (CHF) or atrial fibrillation (AF).
Copyright © 2013 Federation of European Biochemical Societies. Published byElsevier B.V. All rights reserved.
PMID: 24220659 [PubMed - indexed for MEDLINE]
14. Blood. 2010 Dec 2;116(23):5071-2. doi: 10.1182/blood-2010-09-305136.
Increases in B-type natriuretic peptide (BNP) during treatment with lenalidomide in AL amyloidosis.
Tapan U, Seldin DC, Finn KT, Fennessey S, Shelton A, Zeldis JB, Sanchorawala V.
PMID: 21127185 [PubMed - indexed for MEDLINE]
15. J Intern Med. 2008 Mar;263(3):294-301. Epub 2007 Dec 5.
Do troponin and B-natriuretic peptide detect cardiomyopathy in transthyretinamyloidosis?
Suhr OB(1), Anan I, Backman C, Karlsson A, Lindqvist P, Mörner S, Waldenström A.
Author information: (1)Department of Public Health and Clinical Medicine, Umeå University Hospital,Umeå, Sweden. email@example.com
OBJECTIVES: Cardiomyopathy is a well known complication in familial amyloidoticpolyneuropathy (FAP). Troponin T and B-natriuretic peptide (BNP) have been shown to be excellent markers for heart complications in AL-amyloidosis. The aim of thestudy was to investigate troponin T, troponin I and BNP as markers for myocardialdamage and failure in FAP.DESIGN: Retrospective investigation of patients with FAP.SETTING: Tertiary referral centre.SUBJECTS: Twenty-nine patients who had been submitted for evaluation of FAP.INTERVENTIONS: Two-dimensional M-mode and Doppler echocardiography and strainechocardiographic examination. Measurement of Troponin T, troponin I and BNP.RESULTS: Troponin T was detectable in only three patients who all had abnormalinterventricular septal (IVS) thickness. Troponin I was abnormal in six patients (21%), of which only two had an increased IVS thickness. The heart function wasgenerally well preserved in the patients in spite of hypertrophy of the IVS in 14patients. BNP was elevated in 22 patients (76%), and it correlated significantly with IVS thickness and basal septal strain.CONCLUSIONS: Transthyretin amyloid seems to be less harmful to myocytes than thatof AL amyloid as evaluated by serum troponin T and I as well as byechocardiography. BNP appears to be a sensitive marker for cardiomyopathy in FAP,and could prove valuable for follow-up purposes as has been shown forAL-amyloidosis patients.
PMID: 18069997 [PubMed - indexed for MEDLINE]
16. Heart Fail Rev. 2007 Mar;12(1):23-36. Epub 2007 Mar 8.
Interpretation of B-type natriuretic peptide in cardiac disease and othercomorbid conditions.
Burke MA(1), Cotts WG.
Author information: (1)Department of Internal Medicine, Feinberg School of Medicine, NorthwesternUniversity, Chicago, IL, USA.
B-Type natriuretic peptide (BNP) is elevated in states of increased ventricularwall stress. BNP is most commonly used to rule out congestive heart failure (CHF)in dyspneic patients. BNP levels are influenced by age, gender and, to asurprisingly large extent, by body mass index (BMI). In addition, it can beelevated in a wide variety of clinical settings with or without CHF. BNP iselevated in other cardiac disease states such as the acute coronary syndromes,diastolic dysfunction, atrial fibrillation (AF), amyloidosis, restrictivecardiomyopathy (RCM), and valvular heart disease. BNP is elevated in non-cardiac diseases such as pulmonary hypertension, chronic obstructive pulmonary disease,pulmonary embolism, and renal failure. BNP is also elevated in the setting ofcritical illness such as in acute decompensated CHF (ADHF) and sepsis. Thisvariation across clinical settings has significant implications given theincreasing frequency with which BNP testing is being performed. It is importantfor clinicians to understand how to appropriately interpret BNP in light of thecomorbidities of individual patients to maximize its clinical utility. We willreview the molecular biology and physiology of natriuretic peptides as well asthe relevant literature on the utilization of BNP in CHF as well as in otherimportant clinical situations, conditions that are commonly associated with CHFand or dyspnea.
PMID: 17345160 [PubMed - indexed for MEDLINE]
17. Int J Artif Organs. 2006 Aug;29(8):745-9.
Role of B-type natriuretic peptide in cardiovascular state monitoring in ahemodialysis patient with primary amyloidosis.
Fabbian F(1), Stabellini N, Sartori S, Molino C, Russo G, Russo M, Cantelli S,Catizone L.
Author information: (1)Renal Unit, St. Anna Hospital, Ferrara, Italy. firstname.lastname@example.org
BACKGROUND: Cardiac involvement occurs in up to 50% of patients with primary or Aamyloidosis (ALA) and is associated with very poor prognosis. B-type natriuretic peptide (BNP) has been proposed as a guide for treatment of heart failurepatients and as an index of myocardial dysfunction in patients with ALA. Dataabout BNP dosage for cardiovascular monitoring of patients with ALA on renalreplacement therapy are lacking.CASE: A 64 year old Caucasian man was admitted because of nephrotic syndrome inJuly 2003. Renal diagnosis was ALA. Melphalan and prednisolone were given butrenal function worsened and in April 2004 standard bicarbonate hemodialysis wasstarted. In March 2004 thalidomide was added to his therapy. During the follow-upejection fraction was stable and was 65% on the contrary E/A ratio graduallyincreased and overtook 1. BNP plasma levels were increased and the valuesrecorded during the follow-up were: 2505 pg/mL in October 2003 (normal reference values<100), 1827 in April 2004, 4006 in June 2004, 5000 in September 2004, 3750 in January 2005 and 1920 in April 2005. In September 2005 BNP was 3380 pg/mL. Thepatient was still alive after a follow-up longer than two years.CONCLUSION: In ALA patients a powerful prognostic role of BNP has been reportedwhose expression is increased in ventricular myocytes of patients with cardiacinvolvement. BNP level monitoring does not appear to be superior to standardechocardiography in evaluating cardiovascular status of uremic patients with ALA.
PMID: 16969751 [PubMed - indexed for MEDLINE]
18. J Am Coll Cardiol. 1998 Mar 15;31(4):754-65.
Expression of atrial and brain natriuretic peptides and their genes in hearts of patients with cardiac amyloidosis.
Takemura G(1), Takatsu Y, Doyama K, Itoh H, Saito Y, Koshiji M, Ando F, Fujiwara T, Nakao K, Fujiwara H.
Author information: (1)Department of Internal Medicine, Hyogo Prefectural Amagasaki Hospital, Japan.
OBJECTIVES: We investigated the expression of atrial natriuretic peptide (ANP)and brain natriuretic peptide (BNP) and their genes in the hearts of patientswith cardiac amyloidosis and those with isolated atrial amyloidosis.BACKGROUND: The expression of ANP and BNP is augmented in the ventricles offailing or hypertrophied hearts, or both. The expression of ANP and BNP in theventricles of hearts with cardiac amyloidosis, which is hemodynamically similarto restrictive cardiomyopathy, is not yet known. ANP is the precursor protein of isolated atrial amyloid.METHODS: We analyzed the immunohistocytochemical localizations of ANP and BNP as well as the expression of their mRNAs by in situ hybridization in the myocardium and measured the plasma levels of ANP and BNP in patients with cardiacamyloidosis.RESULTS: Four of the five right and all six left ventricular endomyocardialbiopsy specimens obtained from six patients with cardiac amyloidosis wereimmunohistochemically positive for both ANP and BNP; none of the biopsy specimensfrom eight normal subjects were positive for ANP or BNP. All four of the rightatria obtained at operation showed positive immunoreactions for both peptides.Electron microscopy identified specific secretory granules in ventricularmyocytes of the patients with cardiac amyloidosis, but not in ventricularmyocytes from the normal control subjects. Double immunocytochemical analysisrevealed the co-localization of ANP and BNP in the same granules and thatisolated atrial amyloid fibrils were immunoreactive for ANP and BNP, whereasventricular amyloid fibrils were negative for both peptides. Both ANP mRNA andBNP mRNA were expressed in the ventricles of the patients with cardiacamyloidosis but not in the normal ventricles. The autopsy study of four patients with cardiac amyloidosis revealed an almost transmural distribution of ANP andBNP, with predominance in the endocardial side. Plasma BNP levels in the patientswere markedly elevated ([mean +/- SD] 1,165.1+/-561.2 pg/ml) compared with those in the control subjects (8.9+/-6.0 pg/ml, p < 0.05).CONCLUSIONS: Expression of ANP and BNP and their genes was augmented in theventricular myocytes of the patients with cardiac amyloidosis. Both regionalmechanical stress by amyloid deposits and hemodynamic stress by diastolicdysfunction may be responsible for the expression of the peptides in patientswith cardiac amyloidosis.
PMID: 9525543 [PubMed - indexed for MEDLINE]
19. Haematologica. 2011 Jul;96(7):1079-80. doi: 10.3324/haematol.2011.040493. Epub2011 May 23.
Abnormal N-terminal fragment of brain natriuretic peptide in patients with light chain amyloidosis without cardiac involvement at presentation is a risk factorfor development of cardiac amyloidosis.
Wechalekar AD, Gillmore JD, Wassef N, Lachmann HJ, Whelan C, Hawkins PN.
PMCID: PMC3128232PMID: 21606171 [PubMed - indexed for MEDLINE]
20. Am J Cardiol. 2005 Oct 1;96(7):982-4.
Is elevated plasma B-natriuretic peptide in amyloidosis simply a function of the presence of heart failure?
Nordlinger M(1), Magnani B, Skinner M, Falk RH.
Author information: (1)Amyloidosis Treatment and Research Program, Department of Medicine, BostonUniversity School of Medicine, Boston, Massachusetts, USA.
This study sought to determine plasma levels of B-natriuretic peptide (BNP) inpatients with light-chain-associated amyloidosis and correlate them with thepresence or absence of heart failure (HF) and the presence or absence ofechocardiographic abnormalities. Patients with normal echocardiographic resultshad significantly lower BNP levels than those with echocardiographic features of cardiac amyloidosis, whereas BNP levels in the group with HF did not differ from those in patients with asymptomatic cardiac amyloidosis. This observationsupports previous observations, suggesting that the elevation of BNP in cardiacamyloidosis may be due not only to elevated ventricular filling pressure but alsoto direct myocyte damage due to extracellular deposits of amyloid.
PMID: 16188528 [PubMed - indexed for MEDLINE]