amyloidosis and the heart

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Amyloidosisandtheheart-Acomprehensivereview

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REVIEW ARTICLE

Amyloidosis and the Heart

A Comprehensive Review

Keyur B. Shah, MD; Yoshio Inoue, MD; Mandeep R. Mehra, MD

I nfiltration of the heart from insoluble protein deposits in amyloidosis often results in re-strictive cardiomyopathy that manifests late in its course with heart failure and conductionabnormalities. While the rare primary amyloidosis–related heart disease has been well char-acterized, senile amyloidosis occurring in the seventh decade of life most frequently affects

the heart. Early diagnosis of cardiac amyloidosis may improve outcomes but requires heightenedsuspicion and a systematic clinical approach to evaluation. Demonstration of tissue infiltration ofbiopsy specimens using special stains, followed by immunohistochemical studies and genetic test-ing, is essential in defining the specific protein involved. The therapeutic strategy depends on thecharacterization of the type of amyloid protein and extent of disease and may include chemo-therapy, stem cell transplantation, and liver transplantation. Heart transplantation is controversialand is generally performed only at isolated centers. Arch Intern Med. 2006;166:1805-1813

Matthias Schleiden, a German botanist andco-creator of the cell theory, fashioned theword amyloid in 1834 to describe the waxystarch in plants. Today, amyloidosis de-scribes the infiltration of multiple organsby insoluble deposits composed of fibril-lar protein that arise from a diverse groupof disease processes. To date, 24 heterog-eneous proteins prone to misfolding havebeen discovered that comprise amyloid de-posits.1 The misfolded proteins arise sec-ondary to genetic mutations or excess pro-duction and form a �-pleated sheet thataligns in an antiparallel manner. The sheetsform insoluble amyloid fibrils that resistproteolysis and cause mechanical disrup-tion and local oxidative stress in variousorgans.2

Regardless of which precursor proteincauses disease, the deposits are virtuallyindistinguishable with light microscopy.The amorphous proteinacous substancestains pink with Congo red staining, withapple-green birefringence under polariz-ing light microscopy. The spectrum of or-gan involvement can include the kid-

neys, heart, blood vessels, central andperipheral nervous systems, liver, intes-tines, lungs, eyes, skin, and bones.3 Amy-loid deposition in the heart is a devastat-ing and progressive process that leads tocongestive heart failure, angina, and ar-rhythmias. For patients with amyloido-sis, infiltration of the heart confers theworst prognosis. In this systematic re-view, we discuss the clinical features of car-diac amyloidosis, present a diagnostic ap-proach, and describe potential therapies.

CLASSIFICATION

Cardiac amyloidosis is classified by theprotein precursor as primary, secondary(reactive), senile systemic, hereditary, iso-lated atrial, and hemodialysis-associatedamyloidosis. These distinct forms are dif-ferentiated by means of immunohisto-chemical and genetic testing, and prog-nosis and therapeutic strategies differamong these subtypes (Table).

Primary Amyloidosis

In primary amyloidosis (AL), a plasma celldefect produces amyloidogenic immuno-

Author Affiliations: Division of Cardiology, University of Maryland School ofMedicine, Baltimore.

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globulin light-chain proteins, result-ing in an aggressive form of amyloi-dosis. Primary amyloidosis is rare,with an incidence of 8.9 per mil-lion population.4 The mean sur-vival has improved from 4.9 monthsin 1961 to 13.2 months in 1995.5,6

Primary amyloidosis affects moremen than women (3:2), usuallyaround the sixth decade of life.7

Cardiac involvement in AL iscommon, and 60% of patients dem-onstrateelectrocardiographicorecho-cardiographic abnormalities. Clini-cal manifestations of heart failureidentifyamoreaggressivenaturalhis-tory (median survival, 4 months).Death is attributed to cardiac causesinat leasthalfof thepatientswithpri-mary amyloidosis, who die of eitherheart failure or an arrhythmia.6

Light-chain amyloidosis affectsseveral organs, and extracardiacmanifestations often lead to the ini-tial diagnosis. Early in the disease,nonspecific systemic complaints in-cludingweakness, fatigue,andweightloss dominate. Hepatomegaly re-sults from infiltration of the liver orfrom hepatic congestion. Renal in-volvement causes profound protein-uria and nephrotic syndrome. Pur-pura and easy bruising, especially ofthe face and neck, occur from clot-ting factor deficiencies and fragile

venules.Carpal tunnel syndrome,pe-ripheral neuropathy, and macroglos-sia may also be present.6

Laboratory data reveal excesslight-chain protein production. Inone case series, 89% of patients withbiopsy-confirmed primary amyloi-dosis had monoclonal light chainspresent at urine or serum protein im-munofixation electrophoresis. The Mprotein type was primarily � with a2:1 predominance over �. Bone mar-row biopsy can reveal an increasedfraction of plasma cells with prolif-eration of a clonal line and exces-sive � and � light-chain staining.6

Secondary Amyloidosis

Secondary amyloidosis (AA) re-sults from the accumulation of amy-loid A fibrils formed from an acute-phase reactant, serum amyloid Aprotein. Secondary amyloidosis maybe associated with rheumatoid ar-thritis, familial Mediterranean fe-ver, chronic infections, and inflam-matory bowel disease.

Secondary amyloidosis of the heartis typically clinically insignificant.8,9

The primary pathologic findings in-volve the kidney, with developmentof proteinuria and renal failure. Treat-ment of the underlying process canreverse the disease.10

Senile Systemic Amyloidosis

Senile systemic amyloidosis, an age-related disease, occurs in the aorta,heart tissue, brain, pancreas, lung,liver, kidney, and a number of othertissues.11 Wild-type transthyretin(TTR), a transport protein synthe-sized in the liver and choroid plexus,forms the amyloid deposits.12 Se-nile systemic amyloidosis affects menpredominantly, usually after age 70years, and affects the heart in 25%of persons older than 80 years.13 Thedisease is often unrecognized; how-ever, extensive amyloid depositionleads to clinically significant heartfailure. The disease course is less ag-gressive than AL, with a median sur-vival of 75 months.14

Hereditary Amyloidosis

Hereditary (familial) amyloidosis isan autosomal dominant disease inwhich genetically mutated proteinsform the amyloid fibrils. Mutationsin both apolipoprotein I and TTR(ATTR) are known to lead to car-diac involvement, but our focus hereis on TTR mutations, which are moreprevalent.

Variant forms of TTR caused bymore than 80 point mutations in the

Table. Classification of the Subtypes of Cardiac Amyloidosis

Amyloidosis Type ProteinCardiac

Involvement Median Survival, mo Extracardiac Manifestations Diagnostic Testing

Primary (AL) Light chain 22%-34% 13 (4 mo if heart failurepresent at diagnosis)

Renal failure, proteinuria,hepatomegaly, autonomicdysfunction, macroglossia,purpura, neuropathy, carpaltunnel syndrome

SPEP, UPEP,bone marrow biopsy tissueanalysis revealing plasma celldyscrasia, � and � light-chainantiserum staining

Hereditary (ATTR) Mutant TTR Variable 70 Severe neuropathy, autonomicdysfunction, renal failure,blindness

ATTR antiserum staining, serumTTR isoelectric focusing,restriction fragment lengthpolymorphism analysis

Senile systemic(ATTR)

TTR Common 75 Diffuse organ involvement ATTR antiserum staining

Isolated atrial (AANF) Atrial natriureticfactor

Limited to heart . . . None Atrial natriuretic factorantiserum staining

Reactive (AA) Amyloid A �10% 24½ Renal failure, proteinuria,hepatomegaly associatedwith chronic inflammatoryconditions

Target organ biopsy specimenanalysis, AA antiserumstaining

Dialysis-related(�2-microglobulin)

�2-Microglobulin Unknown,asymptomatic

. . . Arthralgias, carpal tunnelsyndrome, arthropathies,bone cysts, pathologicfractures

Synovial and bone biopsyspecimen analysis,�2-microglobulin antiserum,serum �2-microglobulinconcentration

Abbreviations: SPEP, serum protein electrophoresis; TTR, transthyretin; UPEP, urine protein electrophoresis.




DNA predispose the protein to mis-folding and to amyloid formation.15

The prominent feature is peripheraland autonomic neuropathy, a clini-cal entity referred to as familial amy-loid polyneuropathy. Mutations caus-ing significant cardiac disease aremethionine-for-valine substitution atposition 30, serine-for-isoleucine sub-stitution at position 84, and alanine-for-threonine substitution at posi-tion 60.16 While less aggressive thanAL disease, ATTR-related cardiacamyloidosis also results in clinicallysignificant heart failure.

Familial amyloid polyneuropa-thy is generally classified by ances-tral affiliation.17 Over years, pa-tients develop progressive peripheraland autonomic neuropathy. Hyper-esthesia to pain and temperature,motor weakness, and a diminisheddeep tendon reflex ascend from thelower extremities, and patients of-ten become wheelchair dependent.Inactivity masks exertional symp-toms from the underlying cardio-myopathy. Autonomic dysfunctionincludes impotence, decreased bowelmotility, incontinence, and ortho-static hypotension.16

An isoleucine 122 gene muta-tion of the TTR DNA causes a fa-milial amyloidosis primarily involv-ing the heart without neurologicsymptoms and is unique to elderlyblack persons. It is estimated that 1.3million black persons are heterozy-gous for isoleucine 122.18 Presenta-tion of the phenotype is variable, andthe penetrance of the disease has yetto be defined.19

If tissue sampling confirms thepresence of TTR in the amyloid de-posits, isoelectric focusing of the pa-tient’s serum can differentiate mu-tant from normal TTR.20 Genetictesting by restriction fragment lengthpolymorphism analysis can iden-tify the type of mutation.

Isolated Atrial Amyloidosis

Isolated atrial amyloidosis (AANF)is composed of atrial natriuretic pep-tide, a protein secreted by atrial myo-cytes in response to increased wallstretch.21-23 The incidence of AANFincreases with age (�90% in theninth decade of life) and in fe-males.24 The disease also occurs inyoung patients with valvular dis-

ease and in patients with chronicatrial fibrillation.25-27 AANF is lim-ited to the heart as thin, linear de-posits along and underneath the en-docardium. It is unclear whether thedisease process has any clinical sig-nificance.28

Hemodialysis-RelatedAmyloidosis

Patients receiving long-term dialy-sis can develop cardiac amyloidosiswith accumulation of �2-micro-globulin from long-standing ure-mia.29,30 The protein accumulateswith declining renal function and isineffectively cleared with hemodi-alysis. The clinical effect of depos-its occurring in the myocardium,pericardium, and cardiac valves isminimal, and the predominantsymptoms are from joint involve-ment.31,32 Renal transplantation nor-malizes �2-microglobulin concen-trations and improves joint pain.33

PATHOPHYSIOLOGY

While several types of amyloid in-filtrate the heart, only senile, heredi-tary, and primary amyloidosis com-monly cause clinically significantdisease. Amyloid infiltration of theheart interrupts contractile func-tion and electrical conduction andinfluences coronary flow. Amyloidpenetrates the myocardial intersti-tium in the form of nodular depos-its and branching filaments inter-lacing individual myocytes. Earlymild diastolic dysfunction can benoted at echocardiography, but latedisease produces a thickened heartwall with a firm and rubbery con-sistency, worsening cardiac relax-ation and compliance. The stiff heartwall elevates filling pressures, re-sulting in restrictive cardiomyop-athy.34,35 Increased diastolic fillingpressures lead to dilation of the atrialchambers. The less compliant leftventricle remains of normal cham-ber diameter with thickening of thefree wall and septum.36,37 With pro-gression, myocyte necrosis and lo-cal interstitial fibrosis result in sys-tolic ventricular dysfunction. Thedeposition into the atrial walls is ex-tensive and in rare cases can causemechanical failure and conductionstandstill.38,39 Endocardial deposi-

tion may cause valvular insuffi-ciency and worsen congestive heartfailure. In rare cases, pericardial in-volvement occurs with high-gradedisease and can lead to constrictivephysiologic findings.36 There are re-ports of pulmonary amyloid infil-tration resulting in pulmonary hy-pertension and cor pulmonale.40

In addition to mechanical disrup-tion, amyloid deposits induce oxi-dant stress that depresses myocytecontractile function.41 Amyloid alsomodulates interstitial matrix compo-sition and tissue remodeling by dis-abling the balance of matrix metal-loproteinases and their inhibitors.42

Myocardial ischemia results frommicrovasculature disease. Amyloiddeposits spare the epicardial ves-sels, while involvement of the intra-mural vasculature is present in90% of patients with AL amyloido-sis.36,43 Although severe obstruc-tion is rare, diffuse involvement leadsto numerous endocardial foci of is-chemia, microinfarction, and even-tual fibrosis, contributing to fur-ther myocardial dysfunction.44

Direct invasion of the conduc-tion system is rare. However, peri-vascular fibrosis secondary to micro-vascular ischemia commonly involvesthe sinus node and bundle of His.45,46

CLINICAL CHARACTERISTICS

While systemic symptoms of amyloi-dosis are variable, cardiac findings aredominated by diastolic heart failureresulting from restrictive cardiomy-opathy. Findings of right-sided heartfailure predominate, including lowerextremity edema, hepatomegaly, as-cites, and elevated jugular pressure.7

A murmur may be present from val-vular insufficiency, and atrial fibril-lation is common.

Anginal chest pain secondary tomicrovascular involvement withamyloid can also occur. Rare casesof amyloid manifesting as chest painfrom intramural obstruction with-out evidence of myocardial deposi-tion have been reported.47-51

Patients often have syncope andlight-headedness resulting from au-tonomic dysfunction or arrhyth-mia in the setting of poor cardiac re-serve. Amyloid deposition leads toobliteration of adrenergic input intothe heart and alters baseline and




compensatory neurohormonal car-diac stimulation.52 Often, autocor-rection of hypertension is observedas relative hypotension develops.7

DIAGNOSIS

Diagnosis of amyloidosis must beestablished by histologic analysis oftissue. Congo red staining identi-

fies amorphous pink deposits atlight microscopy, which exhibitapple-green birefringence at exam-ination under polarized micros-copy (Figures 1, 2, and 3). If dis-ease is limited to the heart, as inisoleucine 122 hereditary amyloi-dosis, examination of endomyocar-dial biopsy tissue is the only methodof diagnosing the disease. Four en-

domyocardial biopsy samples en-sure near 100% sensitivity for de-tecting disease.53 Less invasive tissuesampling methods are available fordiagnosing systemic amyloid dis-ease. The rectal submucosa has beenthe traditional biopsy site, with a re-ported sensitivity of 75% to 85%, butcan be complicated by bleeding orperforation.54,55 Abdominal fat aspi-ration is without serious complica-tions and is more sensitive (84%-88%) for diagnosing systemicamyloidosis.56-58 Endomyocardial bi-opsy specimens should be ana-lyzed if less invasive methods fail toenable diagnosis of amyloidosis.

Cardiac nonamyloidotic immu-noglobulin deposition disease de-scribes the nonfibrillary depositionof monoclonal immunoglobulinlight chain in the setting of a plasmacell dyscrasia that mimics cardiacamyloidosis. Unlike amyloidosis, thebiopsy specimen appears normal atmicroscopy with negative Congo redstaining, and the disease usually im-proves with resolution of the blooddisorder.59

CARDIAC BIOMARKERS

Serum markers of cardiac injury orstress are often elevated in cardiacamyloidosis. Cardiac-specific tro-ponin serum concentrations may risebecause of myocyte necrosis fromamyloid deposits and ischemia re-lated to intramural vessel obstruc-tion.60 Natriuretic peptide levels arealso elevated secondary to elevatedfilling pressures and possibly myo-cyte necrosis.61,62 Elevations in thetroponin and natriuretic peptidelevels portend a poor prognosis;however, their usefulness in moni-toring disease progression is un-known.63,64

ELECTROCARDIOGRAPHY

Low-voltage QRS amplitudes in theprecordial leads (�10 mV in allleads) or limb leads (�5 mV in allleads), a pseudoinfarction pattern(QS waves in consecutive leads), andconduction delays are common. Thelow-voltage amplitudes in relationto wall thickness result from the dis-placement of viable myocardiumwith amyloid deposits; however,they also occur in other condi-

Figure 1. View of myocardium at microscopy. The amorphous extracellular amyloid deposits (arrow)stain pink, and they disrupt the organization of the heart muscle (hemotoxylin-eosin, originalmagnification �400).

Figure 2. View of myocardium under polarizing microscopy. Amyloid infiltration of the myocardium(arrows) forms an apple-green birefringence under polarizing microscopy owing to the �-pleated fibrillarstructure (Congo red stain, original magnification �100).




tions, including obesity, emphy-sema, hypothyroidism, effusion,myocardial fibrosis, and adrenal in-sufficiency.

Dubrey et al7 reported that elec-trocardiograms for 75% of patientswith cardiac amyloidosis demon-strated a pseudoinfarction pattern,and more than 70% exhibited low-voltage amplitudes. In another se-ries, Murtagh et al65 challenged thesefindings and found that only 47% ofelectrocardiograms demonstrated apseudoinfarction pattern and that46% exhibited low-voltage ampli-tudes. Numerous arrhythmias havebeen described, including atrial fi-brillation, atrial flutter, ventriculartachycardia, atrioventricular block,prolonged QT interval, and junc-tional rhythm.7

ECHOCARDIOGRAPHY

Echocardiography offers a noninva-sive diagnostic approach for moni-toring progression of disease. To ourknowledge, Siqueira-Filho et al66 firstdescribed the “granular sparkling”refractile myocardium pathogno-monic for the disease. Similar stud-ies in patients with symptomatic dis-ease revealed increased ventricularmass with thickening of the ven-tricular septal and free walls. In-creasing wall thickness is inverselycorrelated with survival.67 Septalthickening can often imitate hyper-trophic obstructive cardiomyop-athy.68,69 Increased atrial septal wallthickening and granular sparklingmyocardium are highly specific fordifferentiating cardiac amyloidosisfrom other causes of left ventricu-lar hypertrophy.70 Both atria are typi-cally dilated and the ventricularchamber dimensions are normal.Systolic function can be depressedwith extensive disease.66

Doppler echocardiography pro-vides useful information character-izing the progression of cardiac dys-function. Early amyloid depositionimpairs isovolumetric relaxation, re-sulting in decreased early diastolicflow velocity across the mitral valve(E) and increased dependence onatrial contraction for ventricular fill-ing, leading to increased late dia-stolic filling velocities (A).71 The de-creased E:A ratio of flow velocities isan earlier sign of amyloid involve-

ment. As the heart wall becomes lesscompliant, left atrial pressures in-crease, as does early diastolic fillingacross the mitral valve, thus pseudo-normalizing the E:A ratio.72

The echocardiographic findingsof cardiac amyloidosis mimic othercauses of left ventricular hypertro-phy; thus, it is helpful to combinediagnostic methods to identify car-diac amyloidosis.70 Specifically, com-paring the voltage on the electro-cardiogram with the wall thicknesson the echocardiogram can iden-tify patients with infiltrative cardi-omyopathy (Figure 4). Recentadvances in echocardiography, in-cluding strain and strain rate Dop-pler imaging, may further improve

the sensitivity of detecting cardiacamyloidosis.73

CARDIAC CATHETERIZATION

The coronary angiogram is usuallynormal because only in rare casesdoes amyloid involve the epicar-dial vessels. Right-sided heart cath-eterization enables measurement ofintracardiac pressures for diagno-sis of restrictive cardiomyopathy.Characteristic findings on the he-modynamic profile of extensive amy-loid deposition in the myocardiumare indistinguishable from othercauses of restrictive cardiomyop-athy. Diastolic pressure is elevatedin both ventricles and right-sided

Figure 3. View of cardiac amyloidosis at electron microscopy. Note fibril mesh (arrow) within themyocardium (original magnification �7500).

Concentric Left Ventricular Hypertrophy

Obvious Cause of Increased Left Ventricular Afterload

Low or Normal Voltage Amplitude on ECG

NoYes

Increased Voltage Amplitude on ECG

Hypertension Amyloidosis Fabry Disease

Aortic Valve Stenosis Sarcoidosis Pompe Disease

Hemochromatosis Hypertrophic Cardiomyopathy

Athlete’s Heart

Figure 4. Approach to diagnosis of left ventricular hypertrophy. ECG indicates electrocardiogram.




pressure tracings reveal a dip andplateau or square root sign.

NUCLEAR SCINTIGRAPHY

Scintigraphic evaluation of the heartfor uptake of radiolabeled phospho-nates by amyloid was first exploredmore than 20 years ago.74,75 Sensitiv-ity for diagnosis has been variable;thus, the test has not been incorpo-rated into the routine workup for car-diac amyloidosis.76 A recent study,however, indicates that technetiumTc99m–3,3,-diphosphono-1,2-propa-nodicarboxylic acid may be capableofdifferentiatingTTR-associatedamy-loidosis from AL amyloidosis.77

CARDIAC MAGNETICRESONANCE IMAGING

Cardiac magnetic resonance imag-ing enables high-resolution 3-dimen-sional imaging of the myocardiumand evaluation of chamber diam-eters, wall thickness and consis-tency, and regional wall motion.78 Inaddition, decreased tissue signal in-tensity along with late subendocar-dium tissue enhancement by gado-linium are a result of myocardial

amyloid deposits and can help dif-ferentiate cardiac amyloidosis fromother causes of cardiomyopathy.79,80

Figure 5 shows the clinical and di-agnostic findings that should raisesuspicion for cardiac amyloidosis.

TREATMENT

Medical Therapy

The primary goal of medical therapyis relief of symptoms, and deconges-tion is achieved by cautious diure-sis.Orthostatichypotensionandoblit-eration of sympathetic input precludeuse of negative inotropic agents. Re-ports describe clinical deteriorationwhen cardiac amyloidosis is treatedwith calcium channel blockers.81,82

Similar reasoning extends to �-ad-renergic receptor blockers, but thishas not been demonstrated in theavailable literature. Digoxin binds toamyloid fibrils in vivo, and digoxintoxic effects have been reported.83,84

The binding properties of digoxin toamyloid deposits may disrupt safe ad-ministration of the medication. Pa-tients should be instructed to moni-tor their weight and their fluid and saltintake daily.

Use of Devices

Permanent pacemaker implanta-tion is indicated in patients meetingguidelines for device placement.85

While cardiac pacing improves symp-toms, it has not been shown to im-prove survival.86 No data are avail-able on biventricular pacing orautomatic implantable cardioverter-defibrillators in this population.

Chemotherapy and StemCell Transplantation

Treatment for AL includes oral che-motherapy (melphalan and predni-sone) or high-dose chemotherapywith autologous stem cell transplan-tation. The benefit of oral chemo-therapy is inadequate, and the great-est survival benefits are limited topatients without cardiac involve-ment.87,88

Stem cell transplantation hasshown promising results for thetreatment of primary amyloido-sis.89,90 Compared with other hema-tologic malignancies, transplant-related mortality is increased 5-foldin amyloidosis. The increased mor-tality has been attributed to exten-sive and diffuse systemic end-organ damage from amyloiddeposits, and patients with exten-sive cardiac disease are not optimalcandidates for therapy.89,91

Solid OrganTransplantation

Heart transplantation is not gener-ally accepted as a viable treatment forcardiac amyloidosis because limitedcase series have suggested poor long-term survival as a result of disease re-currence in the allograft; however, ex-tracardiac amyloid disease and sepsisare common modes of death.92,93 Ad-juvant chemotherapy with transplan-tation has not been shown to im-prove mortality, but only limited dataare available for modern regi-mens.94,95 Newer mechanical circu-latory support ventricular assist de-vices may offer an alternativepalliative therapy in end-stage heartfailure as destination therapy, but nospecific use of such devices in amy-loidosis has been reported.96

Liver transplantation removes thesource of mutant TTR and is the only

Consider Tissue Biopsy With Congo Red Stain

EchocardiogramMyocardial Hypertrophy or

Diastolic Dysfunction in the Absence of Valvular Disease or Hypertension

Granular Sparkling MyocardiumBiatrial Dilatation With Normal

Ventricular Chamber Size

Physical ExaminationCHF on Examination

Resolution of HypertensionOrthostatic HypotensionMacroglossiaPeriorbital PurpuraPeripheral Neuropathy

ElectrocardiogramLow-voltage ActivityPseudoinfarction

Cardiac CatheterizationAngiographically Normal

Coronary Vessels With a Dip and Plateau on Pressure Tracing

HistoryChronic FatigueWeaknessSyncopeBreathlessnessChest DiscomfortSharp Extremity PainMotor WeaknessJoint Pain

Laboratory DataElevated Serum Troponin

ConcentrationElevated Serum Natriuretic Peptide

ConcentrationMonoclonol Spike on SPEP/UPEPProteinuriaCoagulopathy

Family HistorySevere NeuropathyHeart Failure at Early Age

Figure 5. Constellation of symptoms and signs and objective data suggestive of cardiac amyloidosis. CHFindicates congestive heart failure; SPEP, serum protein electrophoresis; and UPEP, urine proteinelectrophoresis.




known curative treatment for heredi-tary amyloidosis. More than 500 pa-tients with here ditary amyloidosishave undergone transplantation sur-gery.97,98 Five-year survival is report-edly 60% to 77%, with substantial im-provement in neuropathy.99-102 Ifextensive cardiac infiltration is alsopresent, combined heart and livertransplantation has been success-fully performed in selected pa-tients.103 Early identification of can-didates for transplantation is criticalbecause those with less severe mani-festations of disease burden toleratesurgery better.104

SUMMARY

Cardiac amyloidosis is a rare disor-der that poses a diagnostic chal-lenge because its clinical character-istics overlap with common causesof cardiac disease. Heightened clini-cal suspicion coupled with classicfindings, including low-voltage am-plitudes on electrocardiograms andhyperrefractile myocardium onechocardiograms, typically help inthe diagnosis of late-stage disease.While successful therapeutic inter-ventions are limited, early diagno-sis portends a better response to cur-rent therapy and prolonged survival.Thus, awareness and understand-ing of amyloidosis is important forcardiologists and general practition-ers alike.

Accepted for Publication: May 30,2006.Correspondence: Mandeep R. Me-hra, MD, Division of Cardiology, Uni-versity of Maryland, 22 S Greene St,Room S3BO6, Baltimore, MD 21201([email protected]).Financial Disclosure: None re-ported.Acknowledgment: We thank AllenBurke, MD, for providing the mi-croscopy images.

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Correction

Error in Table. In the Original Investigation by Stewartet al titled “Effect of Exercise on Blood Pressure in OlderPersons: A Randomized Controlled Trial,” published inthe April 11, 2005, issue of the ARCHIVES (2005;165:756-762), there was an error in Table 4. The side head-ings “Abdominal total fat” and “Abdominal visceral fat”should be exchanged, keeping the values where they are.




amyloidosis and the heart

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