AL Amyloidosis Involvement Research Articles

A review of recent clinical trials to evaluate disease-modifying therapies in the treatment of cardiac amyloidosis.

Cardiac amyloidosis (CA) is a serious condition that results in infiltrative cardiomyopathy and heart failure with preserved ejection fraction (HFpEF) that is caused by the extracellular deposition of amyloid fibrils within heart tissue. While many important features of CA have been known for years, its prevalence in elderly patients with HF is increasingly being recognized. Plasma cells produce monoclonal immunoglobulin light chains which results in the formation and aggregation of amyloid fibrils that are responsible for AL amyloidosis. CA is classified as originating from either transthyretin (ATTR) or light chain (AL) amyloidosis. ATTR CA may result from a genetic mutation in the TTR gene, which is inherited (ATTRv), or from age-related deposition from wild-type ATTR (ATTRwt). Cardiac involvement in AL amyloidosis is attributed to either of two mechanisms: the extracellular deposition of amyloid fibril in the myocardium, or direct cardiotoxicity from the fibril aggregates. Typing of amyloid fibrils, a critical determinant of therapy, has also improved with wider availability of laser capture and mass spectrometry of histologic specimens. Specific and accurate evaluation of CA is now possible using cardiac magnetic resonance imaging and bone scintigraphy tracers. Survival in CA has improved markedly as novel chemotherapy agents have become available, but challenges remain in advanced disease. Broadening the amyloid-specific therapeutic landscape to include RNA inhibitors, fibril formation stabilizers and inhibitors, and immunotherapeutic targeting of amyloid deposits holds promise and may improve outcomes in systemic and cardiac amyloidoses. Treatment strategies for CA has recently undergone transformative changes, leading to some progress in outcomes for certain patients. Here, we discuss the basic features of CA as well as the emergence of novel, disease-modifying strategies that have been recently evaluated in clinical trials for the treatment of CA.

Diagnostic performance of liver stiffness as marker of liver involvement in systemic immunoglobulin light chain (AL) amyloidosis.

To investigate the diagnostic performance of liver stiffness for detecting liver involvement in immunoglobulin light chain (AL) amyloidosis. Liver stiffness was measured using transient elastography in 71 patients with systemic AL amyloidosis and 18 patients with wild type transthyretin (ATTRwt) amyloidosis with cardiomyopathy. Both non-invasive consensus criteria and serum amyloid P component (SAP) scintigraphy were used as substitute standards instead of liver biopsy for establishing liver involvement. Liver stiffness was higher in AL amyloidosis patients with liver involvement than in those without: this was observed using both consensus criteria (median 14.4kPa vs. 8.1kPa; p = 0.001) and SAP scintigraphy (median 20.9kPa vs. 6.2kPa; p < 0.001). Liver stiffness was also higher in AL amyloidosis patients with liver involvement compared to AL and ATTRwt amyloidosis patients with cardiac involvement. Based on receiver operating characteristic (ROC) curves a cut-off value of 14.4kPa for stiffness was optimal to indicate liver involvement, providing sensitivity and specificity of 50% and 74%, respectively, using the consensus criteria and 63% and 90%, respectively, using SAP scintigraphy as standard. Liver stiffness is a promising tool to establish liver involvement in AL amyloidosis having potential to become part of updated criteria for liver involvement.

Speckle tracking echocardiography in plasma cell disorders: The role of advanced imaging in the early diagnosis of AL systemic cardiac amyloidosis

IntroductionAmyloid light-chain amyloidosis is a rare condition characterized by the abnormal production of immunoglobulin light chain that misshape and form amyloid fibrils. Over time, these amyloid deposits can accumulate slowly, causing dysfunction in organs and tissues. Early identification is crucial to ensure optimal treatment. We aim to identify a better marker of cardiac amyloidosis, using advanced echocardiography, to improve diagnosis and the timing of available treatments. Materials and methods108 consecutive hematological patients (32, 30% female and 76, 70% male) with a plasma cell disorder referred to our Cardiological center underwent ECG, first and second-level echocardiography (Speckle Tracking) and complete biochemical profile. The best predictors of ALCA (AUC ≥ 0.8) were included in a further analysis stratified by AL score. ResultsAt ROC analysis, the best bio-humoral predictors for the diagnosis of ALCA were Nt-pro-BNP (AUC: 0.97; p < 0.01) and Hs-Tn (AUC: 0.87; p < 0.01). Regarding echocardiography, the best diagnostic predictors were left atrial stiffness (LAS) (AUC: 0.83; p < 0.01) for the left atrium; free wall thickness for the right ventricle (AUC: 0.82; <0.01); left ventricular global longitudinal strain (LVGLS) (AUC: 0.92; p < 0.01) and LVMi (AUC 0.80; p < 0.001) for the left ventricle; and AL-score (AUC 0.83 p < 0.01). In patients with AL-SCORE < 1, LAS (AUC 0.86 vs AUC 0.79), LVGLS (AUC 0.92 vs AUC 0.86) and LV mass (AUC 0.91 vs AUC 0.72) had better diagnostic accuracy than patients with higher AL-score (AL SCORE ≥ 1). ConclusionMulti-parametric imaging approach with LVGLS and LAS may be helpful for detecting early cardiac involvement in AL amyloidosis.

Differences in patient-reported outcomes (PROs) by disease severity in light chain (AL) amyloidosis.

To assess the impact of organ involvement on patient-reported outcomes (PROs) in light chain (AL) amyloidosis. PROs were evaluated using the KCCQ-12, PROMIS-29 + 2, and SF-36 in individuals with AL amyloidosis. The 2004 Mayo system was used to stage disease and cardiac, neurologic, and renal involvement was considered. Global physical and mental health (MH) scores, physical function (PF), fatigue, social function (SF), pain, sleep, and MH domains were evaluated. Effect sizes between scores were measured using Cohen's d. Of 297 respondents, the median age at diagnosis was 60 years with 58% cardiac, 58% renal, and 30% neurologic involvement. Fatigue, PF, SF, and global physical health with PROMIS and SF-36 discriminated the most by stage. Significant discrimination in PROMIS and/or SF-36 was seen in PF, fatigue, and global physical health with cardiac involvement. For neurologic involvement, PF, fatigue, SF, pain, sleep, global physical, and MH with PROMIS and role physical, vitality, pain, general health, and physical component summary with SF-36 were discriminatory. For renal amyloid, pain by SF-36 and PROMIS, and SF-36 MH and role emotional subscales were significant. Fatigue, PF, SF, and global physical health can discriminate stage, cardiac and neurologic, but not renal, AL amyloidosis involvement.

Light-chain cardiac amyloidosis, a condition to consider in daily practice

AL-Amyloidosis is caused by a dysregulated plasma cell clone that produces light chains with a propensity to misfolding and deposition in the target organs. Cardiac involvement in AL amyloidosis is present in up to 70% of cases. We present the case of a 76-year-old woman with a history of surgery for bilateral carpal tunnel syndrome, who presented to the emergency department with a clinical picture of decompensated heart failure. The electrocardiogram showed a low voltage in the limb leads discordant with left-ventricular concentric hypertrophy on the transthoracic echocardiography (TTE). Additionally, TTE demonstrated signs of diastolic dysfunction, mild pericardial effusion, as well as apical sparing on the peak longitudinal strain polar map. The ejection fraction was at 53%. A diagnosis of cardiac amyloidosis was suspected. Serum Kappa and lambda free light chains were elevated with a ratio of 0,02. On nuclear scintigraphy and SPECT, there was no myocardial uptake of the radiotracer Tc99th HMDP. Given the presence of renal involvement consisting of a nephrotic syndrom, the kidney was our biopsy site of choice. The anatomopathological study of the renal biopsy confirmed the diagnosis of AL-amyloidosis. A bone marrow aspirate ruled out concomitant multiple myeloma. For management, the patient received guideline directed medical therapy for HFpEF, along with disease specific therapy consisting of chemotherapy with bortezomib, cyclophosphamide and dexamethasone. Our case highlights the importance of integrating cardiac and extracardiac signs in raising the suspicion of cardiac amyloidosis and prompting specific investigations.

Pulmonary function tests reveal unrecognised lung dysfunction and have independent prognostic significance in patients with systemic AL amyloidosis

Background Lung involvement in AL amyloidosis is not very common, but post-mortem data and retrospective studies suggest it is likely underrecognized. Aim To perform a comprehensive evaluation of lung function with pulmonary function tests (PFTs) in patients with newly diagnosed AL amyloidosis. Methods A prospective, non-interventional study of 139 consecutive patients with newly diagnosed AL amyloidosis. Results PFTs indicated normal breathing physiology in 68% of patients, obstructive in 9% and restrictive in 23%; the latter was associated with worse survival (28.6 vs 76 months for obstructive/normal physiology, p = 0.002) and remained significant after adjustment for Mayo stage and abnormal chest-CT. Forced vital capacity <80% of predicted value, forced expiratory volume <80% of predicted value, and carbon monoxide diffusion capacity <70% were independently associated with poorer survival. Respiratory muscle strength (as assessed by maximal expiratory (Pe) and inspiratory (Pi) pressure) was affected in most patients (64% had Pi < 55% and 57% had Pe < 70% of predicted values). Pe% was an independent prognostic factor for survival (HR: 0.984 per 1% unit increase, p = 0.007). Conclusions Pulmonary dysfunction, as assessed with PFTs, is common and underrecognized in patients with systemic AL amyloidosis, with significant prognostic and potentially therapeutic implications, independent of the degree of cardiac dysfunction or chest-CT findings.

Progression, regression and redefining the treatment response – cardiac magnetic resonance with T1 and extracellular volume mapping in cardiac light-chain amyloidosis

Abstract Background The presence and severity of cardiac involvement in AL amyloidosis is the main driver of prognosis [1]; patients with symptomatic heart failure frequently die within 6 months [1] but median survival has nearly doubled over the past decade, mainly due to significant improvements in chemotherapy. The haematological response to chemotherapy is principally evaluated with serial measurements of serum-free light-chains (FLC) [2]. The cardiac response to chemotherapy is assessed through changes in serum concentrations of brain natriuretic peptides (including NT-proBNP) and echocardiographic parameters [3–5]. Neither are able to directly measure cardiac amyloid burden. Cardiovascular magnetic resonance (CMR) with extra-cellular volume (ECV) mapping can measure the extent cardiac amyloid infiltration [6]. Aims We investigated the ability of CMR to: 1) measure changes in response to chemotherapy; 2) assess the correlation between haematological response (HMR) and changes in cardiac amyloid; 3) assess the association between changes in cardiac amyloid and prognosis over and above existing predictors. Methods In total, 176 patients with cardiac light-chain amyloidosis treated with chemotherapy were assessed with FLC, NT-proBNP and CMR with ECV mapping at baseline (before chemotherapy), 6-months, 12-months &amp; 24-months after commencing chemotherapy. Haematological response was categorized by reductions in FLC as: complete response (CR), very good partial response (VGPR), partial response (PR) or no response (NR). CMR response was categorized by changes in ECV as: progression (≥0.05 increase), stable (&amp;lt;0.05 change) or regression (≥0.05 decrease). Results A progressive increase in patients achieving either CR or VGPR was observed at each time point (61% of patients at 6-months, 71% at 12-months and 80% at 24-months). At 6-months, CMR regression was observed in 3% (all had either CR or VGPR) and progression in 32% (61% had either PR or NR; 39% had either CR or VGPR). At 1-year, CMR regression was observed in 22% (all had either CR or VGPR); progression in 22% (63% had either PR or NR; 37% had either CR or VGPR). At 2-years, CMR regression was observed in 38% (all had CR/VGPR); progression in 14% (80% had either PR or NR; 20% had either CR or VGPR). During follow-up (40±15 months), 36 (25%) patients died. CMR response at 6-months predicted death (progression HR 3.821; 95% CI 1.950–7.487; p&amp;lt;0.001) and remained independently associated with prognosis after adjusting for haematological response, NT-proBNP and longitudinal strain on echocardiography (p&amp;lt;0.01). Conclusions CMR demonstrates that cardiac amyloid deposits frequently regress following chemotherapy, but only in patients who achieve CR or VGPR, highlighting the need for deep haematological response. Changes in amyloid burden (ECV) predict outcomes after adjusting for known predictors, showing the crucial role of CMR in redefining treatment response. Funding Acknowledgement Type of funding sources: Foundation.

Systemic Immunoglobulin Light Chain Amyloidosis Presenting as Painful Penile Ulcers

Immunoglobulin light chain (AL) amyloidosis is a systemic form of amyloidosis that commonly affects the heart, kidney, liver, and nervous system. Penile involvement in AL amyloidosis is rare and thus often not considered in the differential diagnosis for penile ulcers. We report a case of an elderly man with nonhealing, painful penile ulcers who had AL amyloidosis with cardiac, renal, and liver involvement. His penile lesions were successfully treated with surgical resection of the amyloid deposits. Even after serologic relapse of his systemic amyloidosis, he has not had recurrence of his penile ulcers many years later.

Value of repeat renal biopsy in the evaluation of AL amyloidosis patients lacking renal response despite of complete hematologic remission: a case report and literature review

BackgroundsPublished literatures on repeat renal biopsy of AL amyloidosis have basically reached a consensus that amyloid material deposit does not disappear or diminish after satisfactory hematologic response, regardless of renal response. However, the need of a repeat renal biopsy in such situation is still controversial.Case presentationHere we reported a case of histologically confirmed λ Type renal AL amyloidosis who had been classified as Stage I and low risk at initial diagnosis. The patient received a total of six courses of CyBorD chemotherapy. She had achieved complete hematologic remission after two courses of chemotherapy but consistently had large amount of proteinuria over 10 g/day during follow up. A repeat renal biopsy was performed nine months after the first one and indicated mild to moderate increase of amyloid deposits as well as significant glomerulosclerosis and interstitial lesions, suggesting a lack of histological renal improvement despite her satisfactory hematologic response.ConclusionsThis case indicated renal involvement in AL amyloidosis could progress after successful hematologic treatment, and supported the value of repeat renal biopsy in the evaluation of AL amyloidosis patients lacking renal response despite of complete hematologic remission.

Alterations in multi-layer strain in AL amyloidosis

Background Cardiac involvement in AL amyloidosis portends a poor prognosis. 2D-speckle tracking echocardiography (2D-STE) strain can identify subclinical cardiac involvement. This study performed multilayer and multiplanar 2D-STE myocardial strain analysis. Methods We compared 75 AL amyloidosis patients to 49 hypertensive patients and 49 healthy controls. Longitudinal strain was obtained from epicardial, mid-myocardial and endocardial layers; segmental strain was measured from mid-myocardial basal, mid and apical segments. Results Global longitudinal strain was reduced in epicardial (−14.3 ± −4.0% vs. −17.4 ± 2.2% vs. −17.5 ± −2.0%, p < .001), mid–myocardial (−16.3 ± −4.5% vs. −19.7 ± 2.5% vs. −19.7 ± −2.2%, p < .001) and endocardial layers (−18.7 ± −4.9% vs. −22.2 ± 3.0% vs. −22.3 ± −2.6%, p < .001) in amyloid patients compared to hypertensive and healthy controls. Segmental strain confirmed significant reduction in basal (−11.2 ± −3.9% vs. −17.6 ± 2.7% vs. −20.9 ± −3.4%, p < .001) and mid (−14.8 ± −4.3% vs. −19.2 ± 2.5% vs. −19.6 ± −2.2%, p < .001) LV segments in the AL amyloid group. Receiver operating curve analysis demonstrated that an optimal cut-off of −16% for basal segmental strain better differentiated AL amyloid from hypertensive group (sensitivity 96%, specificity 70%, AUC 0.93), compared to relative apical sparing (AUC of 0.85). Conclusion Strain demonstrated myocardial involvement in all layers in AL amyloidosis, with reduced basal segmental longitudinal strain a likely marker of early disease.

P1684 Cardiac amyloidosis hits the valve first

Abstract Case report. 60-year-old man without previous history of coronary artery disease was admitted to our hospital. He complained of weakness, low extremities edema. Physical examination revealed also enlargement of the liver, positive hepatojugular reflux, multiple ecchymoses on patient’s face, especially in periorbital area. The arterial blood pressure was 100/60 mm Hg. ECG showed sinus rhythm 83/min, low R waves in V2, V3 with biphasic T waves in V4-V6. The last coronary angiography revealed normal coronary arteries, it was performed 6 months ago because of atypical chest pain and inconclusive stress test. Echocardiography revealed severe tricuspid regurgitation (TR) due to leaflets restriction and malcoaptation. TR gradient was about 10 mm Hg. Interventricular septum 12 mm, left ventricle posterior wall 9 mm, mass index 87 g/m2, relative wall thickness 0.38; no LV regional wall motion abnormalities was noted, left ventricular ejection fraction (LV EF) was about 50%, mitral valve E/A ratio was 1,4, but average E/E" = 17. Left atrium volume 33 ml/m2. Insignificant amount of pericardial effusion also was found. 3D evaluation of tricuspid valve (TV) showed no leaflets defects and chordal ruptures. LV global longitudinal strain (LV GLS) was – 11,1 % with the apex/(mid + base) ratio 1,3 - apical sparing pattern. Cardiac MRI with gadolinium also showed severe TR and diffuse late subendocardial gadolinium enhancement in both ventricles. We suspected cardiac amyloidosis with significant tricuspid valve involvement, torrential TR, and right ventricle volume overload. The rectum biopsy was negative. The cardiac muscle biopsy with congo red straining was positive for amyloidosis. The patient was transferred to hematology clinic where the diagnosis of AL-amyloidosis was confirmed. The treatment with lenalidomide and prednisone was started. Unfortunately, one month later the patient died. The autopsy was not performed due to religious reasons. Discussion AL-amyloidosis is a systemic disease characterized by multiple organ and tissue changes and associated with poor prognosis. Cardiac involvement is a major prognostic factor as it accounts for approximately 75% of death due to heart failure or arrhythmias. Infiltration of myocardium with amyloid leads to diastolic than systolic dysfunction of the heart and to developing of the heart failure. The most common presentation of heart involvement in AL-amyloidosis is fatigue and dyspnea. In this case the main complaint of the patient was peripheral edema, echocardiography showed damaged TV and preserved LV systolic function. In literature, we found only one case report describing cardiac amyloidosis presented as severe TR. Conclusion In patients presenting with significant isolated valvular dysfunction and heart failure the cardiac amyloidosis can be suspected. The comprehensive echocardiography is the most useful tool to detect this problem. Abstract P1684 Figure. 3D picture of tricuspid valve

Heart involvement in AL-amyloidosis. Current state of the issue

AL cardiac amyloidosis is a relatively rare disorder that belongs to the group of infiltrative cardiomyopathies. Diagnosis of primary amyloidosis is challenging due to many unspecific symptoms and sings, which often leads to late diagnosis when treatment options are limited. Primary amyloidosis particularly needs to be excluded in patients with heart failure with preserved ejection fraction. Therapy in cardiac amyloidosis has to main vectors: 1) chemotherapy to eliminate amyloidogenic plasmatic cells 2) heart failure treatment. The main challenge for cardiologists is to support hemodynamics until response to chemotherapy occurs. In the article the issue of diagnostics, risk stratification and treatment of primary cardiac amyloidosis is addressed.

Diagnostic score of cardiac involvement in AL amyloidosis.

Early diagnosis of cardiac involvement is a key issue in the management of AL amyloidosis. Our objective was to establish a diagnostic score of cardiac involvement in AL amyloidosis and to compare it with the current consensus criteria [i.e. left ventricular hypertrophy >12 mm and N-terminal pro b-type natriuretic peptide (NT-proBNP) >332 ng/L]. We carried out a prospective and multicenter study on AL amyloidosis patients who underwent cardiac evaluation including clinical examination, electrocardiography (ECG), cardiac biomarkers, transthoracic echocardiography (TTE), and cardiac magnetic resonance imaging (CMR). Cardiac involvement was based on CMR and/or endomyocardial biopsy. In a derivation cohort of 114 patients (82 with cardiac involvement), the highest diagnostic accuracy was observed with NT-proBNP and troponin blood levels, TTE-derived global longitudinal strain (LS), and apical to basal LS gradient. By using multivariate analysis, we established a diagnostic score including global LS ≥-17% (1 point), apical/(basal + median) LS ≥0.90 (1 point), and troponin T >35 ng/L (1 point). A score >1 was associated with sensitivity of 94% and specificity of 97%, an area under the curve of 0.98 [95% confidence interval (CI) 0.93-0.99] as well as a net reclassification index of 0.39 (95% CI 0.28-0.46) when compared with consensus criteria. In a validation cohort of 73 AL amyloidosis patients, the area under the receiver operating characteristic curve of the diagnostic score was 0.97 (95% CI 0.90-0.99). Combining T troponin blood levels and two echo-derived strain parameters leads to very high accuracy for diagnosing cardiac involvement in AL amyloid patients.

Clinical features, laboratory characteristics and outcomes of patients with renal versus cardiac light chain amyloidosis.

This study evaluated the differences in clinical features of 1077 newly diagnosed AL amyloidosis patients with renal involvement (n=229, 21%), both cardiac and renal involvement (n=443, 41%) and cardiac involvement (n=405, 38%). Significant differences in dFLC (difference in involved and uninvolved light chains) were noted (renal, both, cardiac median: 83, 234 and 349mg/l, P<0.001). The proportion of patients with≥10% bone marrow plasma cells (BMPCs) was lowest in renal only patients: 44%, 57%, 64%, respectively, P<0.001. In a multivariate linear regression model incorporating organ involvement type and BMPCs ≥10%, organ involvement was a significant predictor of dFLC (P<0.001). Median overall survival (OS) across the three groups was 83 vs. 19 vs. 16months (P<0.001) in patients not undergoing transplant and 5-year OS in patients undergoing transplant was 90% vs. 75% vs. 64% (P=0.007), respectively. In conclusion, renal involvement alone or renal+cardiac involvement in AL amyloidosis is associated with lower circulating light chain burden, which cannot be fully explained by BMPC burden alone. Increased sensitivity of the kidney to light chains, given significant interactions with the renal tubular system and secretion of modified light chain products may play a role in pathogenesis of renal AL amyloidosis and warrants further investigation.

Diagnostic approach to light-chain cardiac amyloidosis and its differential diagnosis

AbstractCardiac amyloidosis is a rare and often-misdiagnosed disorder. Among other forms of deposits affecting the heart, immunoglobulin-derived light-chain amyloidosis (AL amyloidosis) is the most serious form of the disease. Delay in diagnosis and treatment may have a major impact on the prognosis and outcomes of patients. This review focuses on the presentation of the disorder and current novel approaches to the diagnosis of cardiac involvement in AL amyloidosis.

Regional differences in prognostic value of cardiac valve plane displacement in systemic light-chain amyloidosis

BackgroundTo compare the prognostic value of cardiac valve plane displacement (CVPD) on various locations in cardiac light chain (AL) amyloidosis.MethodsConsecutive patients with biopsy-proven cardiac involvement in AL amyloidosis who had undergone cardiovascular magnetic resonance (CMR) between 2005 and 2014 in our institution, were retrospectively identified and data analyzed. The primary combined endpoint was all-cause mortality or heart transplantation. Systolic CVPD were obtained from standard cine bSSFP in 2-, 3- and 4-chamber views at anterior aortic plane systolic excursion (AAPSE); anterior, anterolateral, inferolateral, inferior, inferoseptal mitral (MAPSE); and lateral tricuspid (TAPSE) annular segments.ResultsWe identified 68 patients (58 ± 10 years; 59% male). Median follow-up period was 1.2 years (IQR, 0.3-4.1). Significant differences in CVPD between patients who reached a primary endpoint (n = 44) and transplant-free survivors were found only for AAPSE (6.1 mm (IQR, 4.6-9.4) vs. 8.8 mm (IQR, 6.9-10.4); p = 0.02) and MAPSEanterolateral (7.3 mm (IQR, 5.4-11.7) vs. 10.5 mm (IQR, 8.1-13.4); p = 0.03). AAPSE (χ2 = 15.6; p = 0.0002) provided the best predictive value for transplant-free survival compared to all other valvular plane locations. A high-risk cutoff (AAPSE ≤ 7.6 mm) was calculated by ROC analysis to predict all-cause death or heart transplantation within 6 months from index examination (AUC = 0.80; CI: 0.68 to 0.89; p < 0.0001). AAPSE added incremental prognostic power to an imaging prediction model of late gadolinium enhancement and global longitudinal strain (GLS) (∆χ2 = 5.8, p = 0.02) as well as to a clinical model including Karnofsky index and NT-proBNP (∆χ2 = 6.2, p = 0.01).ConclusionIn patients with cardiac involvement in AL amyloidosis, systolic CVPD obtained from standard long axis cine views appear to indicate outcome better, when obtained in the anterior aortic plane (AAPSE) and provide incremental prognostic value to LGE and strain measurements.

Vertebral compression fractures as the initial presentation of AL amyloidosis: case series and review of literature

The clinical presentation of AL amyloidosis is highly variable. In this series, we describe five cases of AL amyloidosis with vertebral compression fractures as initial presentation. All five patients had evidence of bone marrow replacement on magnetic resonance imaging and bone marrow biopsies demonstrating diffuse interstitial amyloid deposition. Hepatomegaly and elevated liver enzymes, consistent with liver involvement with amyloidosis, were also seen in each case. All five patients responded well to anti-plasma cell chemotherapy, with normalization of serum free light chain levels, reduction in alkaline phosphatase and improvement in pain and functional status. Although rare, AL amyloidosis should be considered in the differential diagnosis of selected patients with spontaneous vertebral compression fractures. Moreover, there seems to be an association of vertebral compression fractures with liver involvement in AL amyloidosis.

Echocardiographic features of an atypical presentation of rapidly progressive cardiac amyloidosis

We present the case of a 66 year old male who presented with dyspnea and reduced exercise tolerance. Echocardiography demonstrated impaired left ventricular (LV) function and restrictive diastolic function with pronounced concentric left ventricular hypertrophy (LVH) without a history of hypertension and no aortic valve stenosis. Differential diagnostics of concentric LVH are discussed in detail. In the current case, cardiac amyloidosis (AL) amyloidosis was diagnosed and confirmed by serum amyloid P (SAP) scintigraphy and abdominal fat aspiration biopsy. This case shows the rapid decline in clinical condition with progression of cardiac involvement of AL. As discussed in detail, cardiac involvement in AL-amyloidosis generally denotes a poor prognosis, regardless of the method of treatment.

Sudden Death Due to Undiagnosed Primary Amyloidosis

Amyloidosis is a disease characterized by abnormal deposition of amyloid protein within tissues throughout the body. The site of deposition can differ between patients, and therefore, clinical presentation can vary. Here, we present a case of previously undiagnosed amyloidosis presenting with sudden death. Autopsy demonstrated amyloid infiltration of intramural myocardial vessels, in the absence of myocardial involvement, leading to acute myocardial infarction and death. Postmortem analysis on femoral blood demonstrated an increase in the concentration of free lambda light chains with a significantly decreased kappa-to-lambda ratio, confirming the amyloidosis to be of AL type. While cardiac involvement in AL amyloidosis is not uncommon, isolated intramural vessel involvement is rarely seen, and to our knowledge, no reported cases have resulted in sudden death. This case highlights the importance of investigating angina-like symptoms in patients with amyloidosis. It also demonstrates that free light chain analysis can be a useful tool for diagnosing and classifying amyloidosis in postmortem investigations.

Abstract 19126: Cardiac AL Amyloidosis with or without Significantly-increased Left Ventricular Wall Thickness

Background: Cardiac involvement is a major prognostic factor in AL amyloidosis. Poor survival of cardiac amyloidosis (CAm) have been reported previously. Recently, many data demonstrate methods detecting early CAm. However, data regarding the clinical meanings of early CAm without significantly-increased LV wall thickness (LVWT) are still lacking. So, we investigated clinical findings of early CAm. Methods: Total 124 patients were diagnosed as AL amyloidosis by positive Congo red stain in tissue. Among them, 46(37.1%) patients satisfied the classic definition of CAm; mean LVWT&gt;12mm without other cardiac cause. And, 19(15.3%) patients had LVWT≤12mm, but were diagnosed as CAm with cardiac biopsy or cardiac MRI. The number of patients without evidence of CAm was 51(41.1%). We compared the echocardiographic parameters as well as survival among three groups. Median follow-up duration was 14.5 months. Results: Mean LVWT was higher in the group of classic definition compared to the group of minor LVWT [14(13∼16) vs 11(9∼12)mm, p&lt;0.003]. However, LV ejection fraction, LA volume index, and e’ were not different between the group of classic definition and of minor LVWT [55.3(46.5∼62.5) vs 54(48∼61)%, p=0.908, 44.0(36.7∼55.1) vs 45.9 (37.7∼58.6)ml/m 2 , p=0.486, 0.04(0.03∼0.06) vs 0.04(0.04∼ 0.05)m/sec, p=0.796]. These parameters were better in the group of no cardiac involvement [65(61∼69)%, 23.5(18.1∼29.7)ml/m 2 , 0.08(0.06∼0.09)m/sec, all p&lt;0.003]. Overall survival rates showed similar pattern. The group of no cardiac involvement showed better prognosis compared to the other two groups (p&lt;0.003). However, between the two groups of CAm, the survival curves were not different (p=0.361). Conclusions: The parameters in echocardiography and survival rates were different according to the presence of CAm, not by the degree of LVWT. The classic definition of cardiac involvement in AL amyloidosis may need to be re-evaluated to reflect more accurate clinical findings.