Diagnosis Of Cardiac Amyloidosis Research Articles

Diagnosis of Cardiac Amyloidosis: Clinical and Echocardiographic Features

This review is geared to address the various forms of amyloidosis which have cardiac involvement and discuss the echocardiographic findings that may be present in patients with cardiac amyloidosis. The use of echocardiography has revolutionized the diagnosis of cardiac amyloidosis. The diagnosis is often first suspected due to characteristic echocardiographic findings. Although no single finding is pathognomonic, there are a constellation of features that point to the diagnosis including increased left and right ventricular wall thickness, thickened cardiac valves and atrial walls, and a pericardial effusion. Alterations in diastolic function with evidence of elevated filling pressures are common. The use of myocardial strain imaging has allowed for earlier detection of cardiac amyloidosis and has revealed a distinctive pattern, sometimes suggesting the diagnosis when more classic findings are subtle or absent. Multiple echocardiographic findings have been found to be prognostic in cardiac amyloid. Using current techniques, functional measures such as myocardial strain and stroke volume index are more powerful predictors of outcome than myocardial thickness. While other imaging modalities are complementary including cardiac magnetic resonance imaging and nuclear medicine scintigraphy techniques using bone tracers, echocardiography remains a mainstay in the diagnosis and follow-up of patients with cardiac amyloidosis. Echocardiography is a critical tool in the evaluation of the patient with heart failure, as well as those with unexplained chest pain and arrhythmias. Key findings on an echocardiogram can help alert the clinician to the presence of cardiac amyloidosis. The degree of cardiac dysfunction in a patient with systemic amyloidosis correlates with prognosis. Recognition of subtle echocardiographic findings may allow for earlier and more aggressive treatment to improve overall mortality in patients with cardiac amyloidosis.

1161Accuracy of non contrast magnetic resonance for clinical diagnosis of cardiac amyloidosis - a 868 patient prospective study

1161Accuracy of non contrast magnetic resonance for clinical diagnosis of cardiac amyloidosis - a 868 patient prospective study

Quantification of Myocardial Enhancement on Cine-MRI: Diagnostic Value in Cardiac Amyloidosis

Diagnosis of cardiac amyloidosis (CA) on cardiac magnetic resonance (CMR) can be challenging and quantitative indexes are relevant to further characterize the myocardium. We hypothesize that the relative myocardial enhancement measured from pre and post contrast cine imaging provides diagnostic information for CA in the setting of left ventricular hypertrophy (LVH). Patients with LVH referred to our center and control subjects with normal CMR were retrospectively included. Percentage of myocardial enhancement (percentage ME) was obtained from pre and post contrast (5 minutes) cine sequences. Post contrast myocardial T1 and LGE extent were also recorded. Twenty-one patients with CA, 25 patients with non-amyloid left ventricular myocardial hypertrophy (CH) and 20 controls with normal CMR were analyzed. Percentage ME was significantly higher in CA patients (200% (174-238)) than in CH patients (122% (88-151); p = 0.0001) and control patients (104% (90-149); p = 0.0001). Percentage ME was significantly correlated with the LGE extent (Rho Spearman coefficient = 0.66; p = 0.0001) and with the post contrast myocardial T1 (Rho Spearman coefficient = -0.61; p = 0.0001). With a cutoff value of 152%, the sensitivity and specificity of percentage ME for detection of CA were 90% and 80%, respectively. Percentage ME obtained from pre and post contrast cine imaging is correlated to LGE extent and myocardial T1 and may represent an additional diagnostic parameter to consider CA in patients with LVH.

NUCLEAR IMAGING IN THE DIAGNOSIS OF CARDIAC AMYLOIDOSIS

Histological analysis of endomyocardial tissue is still the gold standard for the diagnosis of cardiac amyloidosis but has its limitations. Accordingly, there is a need for noninvasive techniques to cardiac amyloidosis diagnostics. Echocardiography and magnetic resonance imaging can show characteristics which may not be very specific for cardiac amyloid. Recently, new opportunities of nuclear imaging in risk stratification and assessment of prognosis for patients with cardiac amyloidosis have appeared. During the last two decades different classes of radiopharmaceuticals have been developed based on compounds tropic to the components of amyloid infiltrates. In this paper we describe the current possibilities and perspectives of nuclear medicine techniques in patients with cardiac amyloidosis, including osteotropic and neurotropic scintigraphy, single-photon and positron emission tomography

Amyloid Heart Disease

Cardiac amyloidosis is a group of disorders that develop secondary to the deposition of misfolded proteins in the heart. It can occur in isolation or as part of a systemic disease and can be inherited or acquired. Amyloid light chain (AL) and amyloid transthyretin (ATTR) are the two main forms of amyloid proteins that can infiltrate the heart. With the increased use of advanced imaging techniques and protocols, the recognition and diagnosis of cardiac amyloidosis, especially ATTR, has become easier. New therapies intended to improve survival and quality of life in patients with cardiac amyloidosis are emerging. This article provides an up-to-date review of cardiac amyloidosis.

Role of cardiovascular magnetic resonance in suspected cardiac amyloidosis: late gadolinium enhancement pattern as mortality predictor.

BackgroundCardiac magnetic resonance (CMR) has gained a central role in the diagnosis of cardiac amyloidosis (CA). While the diagnostic role of a typical late gadolinium enhancement (LGE) pattern (global subendocardial enhancement coupled with accelerated contrast washout) has been identified, evidence is still conflicting regarding the prognostic role of such examination.Methods and resultsWe retrospectively analysed all patients referring for CMR at Niguarda Hospital (Milan, Italy) from January 2006 to January 2015 for suspected CA. Primary outcome was all-cause mortality. We identified 42 patients and divided them into 2 groups, according to the presence (Group A) or absence (Group B) of a typical amyloidosis LGE pattern. At the end of the follow-up (median 37 months, interquartile range 10–50 months), 31 patients (74%) had died. The hazard ratio for all-cause death was 3.2 (95% confidence interval [CI] 1.5–6.4, p < 0.01) for Group A versus Group B. Median survival time was 17 months (95% CI 7–42 months) for Group A and 70 months (95% CI 49–94 months) for Group B (p < 0.01). Multivariate analysis did not find any adjunctive predictive role for biventricular volumes and ejection fraction, indexed left ventricular mass, transmitral E/e’ at echocardiography, age at diagnosis or serum creatinine.ConclusionIn our population, a typical LGE pattern was significantly associated with higher mortality. Moreover, patients with a typical LGE pattern showed a globally worse prognosis. Our data suggest that the LGE pattern may play a central role in prognostic stratification of patients with suspected CA, thus prompting further diagnostic and therapeutic measures.

P6128Combined role of left ventricular longitudinal strain and atrial compliance in the differential diagnosis of cardiac amyloidosis in primary and secondary ventricular hypertrophy

P6128Combined role of left ventricular longitudinal strain and atrial compliance in the differential diagnosis of cardiac amyloidosis in primary and secondary ventricular hypertrophy

Assessment of cardiac amyloidosis by using 18f-sodium fluoride PET/MR imaging

Purpose Cardiac amyloidosis exists in two predominant forms called acquired monoclonal immunoglobulin light-chain (AL) and transthyretin-related (ATTR). Their differentiation is a real diagnostic challenge for treatment management and prognosis of patient. Magnetic resonance (MR) imaging is increasingly used to aid in the diagnosis of cardiac amyloidosis on the basis of characteristic appearances on late Gadolinium enhancement (LGE) but cannot distinguish ATTR and Al forms. Several series have showed that scintigraphy using bone 99mTc-bisphosphonate tracers preferentially bind ATTR versus AL myocardial deposit. Our aim was to use 18F-Sodium Fluoride (18F-NaF) positron emission tomography (PET) bone tracer in hybrid PET/MR imaging to aid in both the diagnosis of cardiac amyloidosis and differentiation of ATTR and AL forms within a single scan. Methods Consecutive patients with biopsy-proven ATTR or AL cardiac amyloidosis and as many healthy control subjects were included. All patients underwent simultaneous PET/MR (BiographTM mMR, Siemens) scans after IV injection of 370MBq of 18F-NaF. The selected data were reconstructed using a 3D breath-hold Dixon MR attenuation correction map. MR protocol included LGE sequences, pre- and post-contrast T1 mapping. Maximal target-to-background ratio (TBRmax) was recorded, defined as maximal myocardial FDG uptake (SUVmax) corrected for mean right atrium blood pool activity. Mean TBRmax in ATTR, AL and controls were compared using a Student t-test. The institutional review board approved the study and all patients gave written informed consent. Results Eighteen patients (61.3 ± 10.5 yo, 12 M/6F) were prospectively recruited (6 ATTR, 3 AL and 9 controls). All amyloid patients had characteristic LGE appearances. Mean TBRmax were respectively 1.29 ± 0.31, 0.77 ± 0.06 and 0.68 ± 0.03 in ATTR, AL and control subjects. Mean TBRmax was significantly higher in ATTR than in AL patients ( P = 0.028) and in controls ( P = 0.0001). Mean TBRmax was significantly higher in AL patients than in controls ( P = 0.046). A TBRmax threshold of 0.85 appeared to differentiate all patients as having ATTR amyloidosis. There was no significant difference in terms of pre-contrast ( P = 0.48) and post-contrast T1 mapping ( P = 0.57) between ATTR and AL patients. Conclusion These results showed the potential of 18F-NaF PET/MR to diagnose cardiac amyloidosis and to differentiate ATTR and AL forms, confirming our preliminary published results (Trivieri et al. JACC 2016)

Cardiac Amyloidosis: An Updated Review With Emphasis on Diagnosis and Future Directions

Cardiac amyloidosis occurs because of abnormal protein (amyloid) deposition in the cardiac tissue. Even with advanced diagnostic techniques and treatments, the prognosis of amyloidosis remains poor. The diagnosis of cardiac amyloidosis particularly needs to be in the differential in patients presenting with heart failure with preserved ejection fraction. This entity remains underdiagnosed due to lack of suspicion on the part of many clinicians. Involvement of cardiac tissue is the utmost determinant factor for available treatment options and prognosis. Many cases of cardiac amyloidosis usually remain undiagnosed or diagnosed only in advanced stages when treatment options are limited and associated with poor survival. Hence, early recognition of cardiac amyloidosis is indispensable in halting the disease process before irreversible changes occur. The purpose of this review is to summarize the recent updates in the evaluation and management of cardiac amyloidosis and to discuss potential future treatments options.

Cardiac cmyloidosis: case report

Amyloidosis is a result of the extracellular deposit of seric proteins (amyloid) and almost all organs can be compromised. Cardiac amyloidosis is usually a progressive cardiomyopathy that has a bad prognosis. We present here a case report about a patient that had signs and symptoms of heart failure and left ventricle hypertrophy. Because it was not possible to make the diagnosis of cardiac amyloidosis in time, he died. This disease must be considered when no other cause for those findings exists

The Utility of 99mTc-DPD Scintigraphy in the Diagnosis of Cardiac Amyloidosis: An Australian Experience

The uptake of bone-seeking radiotracers in the amyloid heart is well recognised. 99mTc-DPD has been shown to be highly sensitive for cardiac transthyretin (ATTR) amyloid in an overseas population, but is not registered for use in Australia. We explored its utility as a diagnostic tool within our population. Patients diagnosed with AL and ATTR (wild-type and inherited) cardiac amyloidosis were prospectively recruited from the Princess Alexandra Hospital Amyloidosis Centre. Patients underwent injection with 99mTc-DPD then planar whole body imaging was performed at 5 minutes post-injection (soft tissue phase) and 3 hours (bone phase). A myocardial SPECT and low amperage CT were acquired after the late whole-body scan. Scans were analysed by two nuclear imaging specialists. Intensity of cardiac 99mTc-DPD uptake was graded as 0 to 3 in accordance with previous criteria, and semiquantitative analysis was performed using a heart to whole body ratio (H:WB) on the 3-hour scan. Patients also underwent electrocardiography and transthoracic echocardiography, and blood samples were taken for troponin I and brain natriuretic peptide levels, to assess for any correlation with DPD uptake. Twenty-one patients (8 AL and 13 ATTR) completed the study. Median age was 58 and 70 years for AL and ATTR patients respectively, and 19 (90.5%) were male. 99mTc-DPD scintigraphy was positive in 2 (25%) of AL, and 13 (100%) of ATTR patients. Grade of cardiac uptake, and mean H:WB (0.1249 v. 0.0794) was greater in the ATTR cohort (p-value<0.001 and 0.001 respectively). No statistically significant correlation was identified between H:WB and echocardiographic parameters. There was a significant positive correlation between H:WB and the PR interval on ECG (p=0.026). 99mTc-DPD scintigraphy is highly sensitive for the diagnosis of cardiac ATTR amyloid, but less so for AL amyloid.

Native T1 mapping for the diagnosis of cardiac amyloidosis: a pilot research

Objective To explore the potential role of native cardiac T1 mapping by cardiac magnetic resonance for detection of cardiac amyloidosis (CA). Methods Twenty patients with cardiac amyloidosis (with definite cardiac involvement based on standard biomarkers and echo cardiographic criteria) were studied at our hospital from 2012 to 2013. Comparisons were made with 20 healthy volunteers and 40 patients with hypertrophic cardiomyopathy (HCM). All underwent CMR (1.5 T) including native T1 mapping MOLLI (modified Look-Locker inversion recovery) sequence and LGE (late gadolinium enhancement) imaging. Analysis of variance was performed to analyze the differences between groups regarding native T1 and LV mass.ROC curve analysis was performed to define a T1 relaxation time cutoff value that identifies CA with the greatest sum of sensitivity and specificity. Correlation between T1 and cardiac function indices was assessed using Pearson test. Statistical significance was defined as P<0.05. Results Cardiac T1 was significantly elevated in CA patients [(1 124±49) ms] compared to normal subjects [(973±39) ms] and patients with HCM [(1 045±50) ms](F=44.75, P<0.01). The cut off value to diagnose CA was 1 082 ms with specificity 80% and sensitivity 75%. The cut off value to rule out CA was 1 012 ms with sensitivity 100% and specificity 40%).There was significant correlation between native T1 relaxation timesand indices of systolic and diastolic function in the CA cohort. As T1 relaxation times increased, LV ejection fraction decreased (r=-0.51, P<0.01) and LV mass index increased (r=0.52, P<0.01). Conclusion Native T1 mapping may have potential as a valuable method for diagnosing and quantifying CA. Key words: Amyloidosis; Myocardium; Magnetic resonance imaging

99m Technetium-Hydroxy-Diphosphate Tracer (99mTcHDP) Bone Scintigraphy: An Easily Accessible, Rapid, Non-Invasive Diagnostic Tool for Cardiac Amyloidosis

Aim:Cardiac amyloidosis is a protein deposition disease that can be difficult to diagnose and has a poor prognosis if diagnosis or treatment are delayed. The two major subtypes are AL and transthyretin (ATTR). Both have vastly different treatments so confirming the correct amyloid subtype is crucial.A tissue biopsy is usually required for the diagnosis of amyloidosis and to distinguish between the subtypes. No blood test, echocardiography or cardiac MRI can reliably distinguish between AL and ATTR. With a cardiac biopsy, distinguishing AL from ATTR can be challenging with immunohistochemistry, and time consuming with mass spectrometry.Recently, Gillmore et al demonstrated bone scintigraphy with 99mTc-DPD tracer can reliably diagnose ATTR, avoiding endomyocardial biopsies to confirm the subtype in most cases.[1] 99mTc-HDP is a tracer similar to 99mTc-DPD and is more readily available in Australian and the USA.We sought to examine the use of 99mTcHDP bone scintigraphy in Australia and determine the accuracy of this tracer to diagnose cardiac amyloidosis and distinguish between the AL and ATTR subtypes.Methods:All patients with confirmed ATTR or AL who had 99mTcHDP bone scintigraphy were analysed. Results were correlated with histology, NT ProBNP, Troponin-T, free light chains, cardiac MRI and echocardiography. Grading was conducted with Perugini scoring.[1]Results:25 patients with amyloidosis diagnosed by cardiac MRI and/or biopsy, had 99mTcHDP bone scintigraphy. 18 were confirmed ATTR, 7 AL. Two ATTR patients had hereditary disease (Thy60Ala and Gly109Lys), the remainder were wildtype.17 (94%) patients with ATTR and 2 (29%) AL had positive scans. The negative ATTR patient had localized bladder disease only with a normal echocardiogram and cardiac biomarkers. All ATTR patients with positive scans had Perugini scores of 2 or 3, including the 2 patients with hereditary mutations, while the two positive AL only had scores of 1. All 11 patients with amyloid features on cardiac MRI had positive scans.Mean NTproBNP values for ATTR and AL were 530pmol/L and 1396pmol/L respectively. The two AL amyloidosis patients with positive bone scans had higher NTproBNP values. No ATTR patient had a detectable plasma cell dyscrasia.Conclusion:Bone scintigraphy with 99mTcHDP tracer is an easily accessible, rapid and non-invasive method of diagnosing cardiac amyloidosis. In our small series, all patients with Perugini scores 2 or 3 had ATTR, while those with negative or Perugini score 1 scan either had AL or no cardiac amyloidosis. There was a suggestion that AL patients with higher NTproBNP scores were more likely to have positive scans.This suggests that the 99mTcHDP tracer can be used like 99mTc-DPD to aid in the diagnosis of cardiac amyloidosis, and, as suggested by Gillmore et al, can confirm the ATTR subtype in those with no detectable plasma cell dyscrasia and Perugini score 2 or 3 scans, thus hastening accurate diagnosis and avoiding cardiac biopsies.Reference:Gillmore JD, Maurer MS, Falk RH, Merlini M, Damy T, Dispenzieri A, et al. Non-biopsy diagnosis of cardiac transthyretin amyloidosis. Circulation. 2016 Jun 14;133(24):2404-12 DisclosuresNo relevant conflicts of interest to declare.

Myocardial strain pattern in patients with cardiac amyloidosis secondary to multiple myeloma: a cardiac MRI feature tracking study.

Cardiac MRI is frequently used in the diagnosis of cardiac amyloidosis. Feature tracking is a novel method of analyzing myocardial strain at the myocardial borders. We investigated myocardial deformation mechanics of both the right and left ventricles in patients with multiple myeloma with suspected cardiac amyloidosis. Comprehensive strain analysis was performed in 43 patients with multiple myeloma and suspected cardiac amyloidosis. MRI strain by feature tracking was measured using 2D cardiac performance analysis MR software (Tomtec, Germany). Global longitudinal (GLS) and global circumferential (GLC) strain were calculated in endo and epicardium. In addition, right ventricular longitudinal strain was measured in the endocardium only. All patients later underwent endomyocardial biopsy. Average wall thickness in biopsy proven cardiac amyloidosis group (22 patients) was 1.4 ± 0.4cm with wall thickness ≤ 1.2cm in 36 %. LGE was present in all patients with biopsy confirmed disease. There was significantly decreased global longitudinal strain and strain rate in the epicardial and endocardial layers. Global circumferential strain was significantly reduced in the epicardial layer but not the endocardium. GLS was significantly decreased at the base in both layers compared to the mid and apical regions of the myocardium. However, the base to apex GLS gradient was suggestive of apical sparing in the endocardial layer among patients with amyloidosis (-8.2 ± 2 vs. -2.7 ± 1; p = 0.001) but not the epicardial layer. Apical sparing was evident even in those with normal thickness CA. This feature tracking MRI analysis sheds light on strain mechanics in a cohort of multiple myeloma associated cardiac amyloidosis with a significant number of cases with normal LV wall thickness and explains mechanism of apical sparing effect.

Recent advances in the noninvasive strategies of cardiac amyloidosis.

The heart, like any organ in the body, is susceptible to amyloid deposition. Although more than 30 types of protein can cause amyloidosis, only two types commonly deposit in the ventricular myocardium: amyloid light chain and amyloid transthyretin. Amyloid cardiomyopathy is usually a major determinant of patient outcomes, and the diagnosis of heart involvement can be often relatively under-diagnosed, owing to nonspecific presenting symptoms and signs at a subclinical stage. The diagnosis of cardiac amyloidosis is usually performed by endomyocardial biopsy; however, the invasive nature and related high-risk complications restrict its wide use in clinical settings. Recently, with the advent of innovative techniques used for evaluating cardiac amyloidosis, noninvasive methods become increasingly important, especially in earlier diagnosis, distinguishing typing, risk prediction and response to treatment. Here, we will review recent developments in the noninvasive methods used in the assessment of cardiac amyloidosis, focused on the laboratory biomarkers and imaging modalities.

Use of Noninvasive Imaging in Cardiac Amyloidosis.

Cardiac involvement in amyloidosis is associated with poor outcomes. The standard test for the diagnosis of cardiac amyloidosis is endomyocardial biopsy but given current advances in noninvasive imaging, the diagnosis is frequently obtained or strongly suspected without biopsy. Echocardiography is the most utilized cardiac imaging modality, particularlymyocardial strain measures with this modality have been found to be a predictor of clinical outcomes, superior to traditional parameters. Other known imaging modalities with new, useful protocols for this pathology include nuclear imaging and cardiac magnetic resonance (CMR). In particular, CMR has excellent sensitivity and specificity.

3.0T Cardiac Magnetic Resonance Quantification of Myocardial Extracellular Volume using different delay time of post-contrast T1 mapping for the Diagnosis of Cardiac Amyloidosis

3.0T Cardiac Magnetic Resonance Quantification of Myocardial Extracellular Volume using different delay time of post-contrast T1 mapping for the Diagnosis of Cardiac Amyloidosis

Orthotopic Heart Transplant Facilitated Autologous Hematopoietic Stem Cell Transplantation in Light-Chain Amyloidosis

Dominant cardiac involvement by primary systemic amyloidosis (AL) precludes effective AL treatment and is associated with short survival. Between January 2009 and June 2015, total of 9 patients who presented with severe cardiac dysfunction as their major manifestation of AL underwent orthotopic heart transplantation (OHT). Four of these 9 patients were able to complete the planned second phase of treatment with autologous hematopoietic stem cell transplantation (ASCT) 13-16 months after OHT. Diagnosis of cardiac AL was established via endomyocardial biopsy, Congo red staining and immunohistochemistry. All patients had end stage heart failure and developed cardiogenic shock requiring intra-aortic balloon pump support (median 20 days, range 10-165) as a bridge to OHT.The median age at AL presentation was 54 years (42-65) in 4 females and 5 males. At median follow-up of 30 months (1-54) from OHT, 6 (66 %) patients are alive (table-1). Two patients died of post-operative complications at 1 and 7 months post OHT; a 3rd patient died 36 months after OHT (23 months post ASCT) of AL progression. Four patients received ASCT at median of 13 months (13-16) after OHT. In the remaining 3 patients ASCT was not feasible due; to low DLCO; recently treated disseminated Cryptococcus; or prior ASCT.All 4 patients with ASCT were on tacrolimus and prednisone at the time of stem cell mobilization and hematopoietic transplant; two patients were also receiving mycophenolate mofetil and valganciclovir. We collected 5.7, 6.1 and 6.2 x 106/kg CD-34+ cells in 2 days after filgrastim administration (5 ug/kg, twice, daily) and plerixafor (16 mg/kg based on day- 4 CD-34+ counts) in 3 subjects. The fourth patient initially failed to mobilize but 4.3x106/kg CD-34+ cells were subsequently obtained after stopping mycophenolate mofetil for 4 weeks. The creatinine clearance at the time of the high-dose chemotherapy given prior to ASCT was 36, 30, 41 and 43 ml/minute. All 4 patients received a renal adjusted dose of melphalan at 140mg/m2. Mycophenolate mofetil and valganciclovir were withheld during neutropenia until engraftment. No patients received post-transplant filgrastim. Patients were hospitalized for 17, 18, 18 and 20 days. Renal function remained stable during ASCT and non-hematological toxicity was limited to grade I-II apart from one grade III oral mucositis and colitis. Two patients achieved hematologic complete remission (patient2&4) while 2 patients had a partial response following ASCT. Post OHT and ASCT 3 patients are alive and well at follow-up of 54, 37 and 52 months.The strategy of OHT followed by ASCT is therefore feasible in select patients with dominant cardiac involvement and advanced heart failure DisclosuresNo relevant conflicts of interest to declare.

Abstract 18563: The Role of a Change in ECG Voltage on the Diagnosis and Prognosis in Cardiac Amyloidosis

Background: Low voltage on ECG may be caused by various medical conditions. In cardiac amyloidosis, low voltage in the limb leads is found in approximately 50% with AL and only 20-25% of ATTR, whether senile or familial. Despite not meeting low voltage criteria on ECG, a reduction of voltage over time may signify amyloid cardiomyopathy. Methods: The electrocardiograms of consecutive patients at the time of a diagnosis of cardiac amyloidosis at our institution were analyzed. Patients with ventricular paced rhythms were excluded. An additional ECG at least one year prior to the diagnosis was also analyzed. The sum of voltage in all limb leads and the Sokolow voltage (S wave in V1 plus R wave in V5 or V6) index were calculated. Low limb voltage was defined as ≤ 5 mm in all limb leads and low precordial voltage as ≤ 10 mm in all precordial leads. A Cox proportional hazards model was used to assess the correlation between decreasing ECG voltage and 3 year mortality. Results: A total of 338 patients (192 AL, 146 ATTR, age 68.7 +/- 12.1 years, obese 57%, HTN 54%) were identified. At the time of diagnosis, 167 patients (49.4%) met either low limb or low precordial voltage criteria. The limb lead voltage decreased in 63 of 73 patients (86.3%) and the Sokolow voltage decreased in 62 of 73 patients (84.9%). The mean overall decrease in limb lead voltage was 10.6 +/- 12.6 mm overall or 3.3 +/- 4.6 mm per year. The Sokolow voltage decreased 6.5 +/- 7.1 mm overall or 1.8 +/- 2.3 mm per year. On univariable analysis, the annualized decrease in Sokolow voltage showed a non-significant trend towards an increase in mortality. Conclusion: A decrease in voltage on serial ECG’s is more prevalent than low voltage in cardiac amyloidosis. There is a trend towards increased mortality in patients who have a greater decrease in voltage over time. The evaluation of serial ECG’s for changes in voltage is important to recognize in the diagnosis of cardiac amyloidosis and may have prognostic value.

Orthotopic Heart Transplant Facilitated Autologous Hematopoietic Stem Cell Transplantation in Light-chain Amyloidosis

Abstract Abstract 4489 Dominant cardiac involvement by primary systemic amyloidosis (AL) precludes effective AL treatment and is associated with short survival (median survival for stage-III AL= 3–4 months). Three patients who presented with severe cardiac dysfunction as their major AL manifestation underwent orthotopic heart transplantation (OHT) followed by autologous hematopoietic stem cell transplantation (ASCT). The clinicopathological characteristics of these patients form the basis of this report. Age at AL presentation was 63, 62 and 44 years in 2 females and 1 male. The time from initial symptoms of AL to diagnosis was 12, 24 and 12 months. Diagnosis of cardiac AL was established via endomyocardial biopsy, Congo red staining and immunohistochemistry. Standard work-up for plasma cell dyscrasia included; serum and urine electrophoresis, immunofixation, measurement of serum-free light-chain ratio and bone marrow biopsy. All patients had stage III AL based on cardiac troponin I and NT-pro-BNP. All had end stage heart failure with New York Heart Association class 4 symptoms and developed cardiogenic shock requiring intra-aortic balloon pump support as a bridge to OHT. All were considered unsuitable for ASCT. Initial treatment was with lenalidomide, dexamethasone in two patients while the third received melphalan and dexamethasone. Table -1 shows the timeline of diagnosis and dual transplants. Table-1: . Orthotropic cardiac transplantation (OHT) followed by ASCT Age/Sex Time to AL diagnosis (months) Organ involvement (months) Time * to OHT (months) Time to ASCT s/p OHT (months) Survival (months) 63/F 12 Heart, Kidney, PN 7 13 30+ 62/F 24 Heart, Kidney, PN 5 16 26+ 44/M 12 Heart, Kidney, tongue 4 13 14+ * Time to OHT from onset of heart failure symptoms, PN= peripheral nerve, F = female, M= male, s/p= status post ASCT was performed 13, 16 and 13 months after OHT. All 3 patients were on tacrolimus and prednisone at the time of stem cell mobilization and hematopoietic transplant; two patients were also receiving mycophenolate mofetil and valganciclovir. We collected 6.1 and 6.2 × 106/kg CD-34+ cells in 2 days with filgrastim (5 ug/kg, twice, daily) and plerixafor (16 mg/kg based on day- 4 CD-34+ counts) in two subjects. The third initially failed to mobilize but 4.3×106/kg CD-34+ cells were subsequently obtained when she (patient #2) was remobilized with filgrastim and plerixafor 4 weeks after stopping mycophenolate mofetil. The creatinine clearance at the time of high-dose chemotherapy was 36, 30 and 43 ml/minute. All 3 patients received renal adjusted dose of melphalan at 140mg/m2. Mycophenolate mofetil and Valganciclovir were withheld during neutropenia until engraftment. Time to engraftment for neutrophils (ANC of >500/uL x3 days) was 13, 11 and 14 days. Platelets engraftment (untransfused >20 × 109 for 3 consecutive days) occurred in 14, 13 and 16 days. No patients received post-transplant filgrastim. Patients were hospitalized for 17, 18 and 18 days. Renal function remained stable during ASCT and non-hematological toxicity was limited to grade I-II apart from one grade III oral mucositis and colitis. One patient achieved hematologic complete remission (patient#2) while 2 patients had partial response following ASCT. Post OHT and ASCT all patients are alive and well at follow-up of 14, 26 and 30 months from OHT. OHT should be considered in select patients with dominant cardiac involvement and advanced heart failure to allow subsequent ASCT and improve survival. Disclosures: No relevant conflicts of interest to declare.