Pyrophosphate Scan Research Articles

Cardiac Amyloidosis Masquerading as Hypertrophic Obstructive Cardiomyopathy: Co-existence or Coincidence?

Abstract A 59-year-old male presented with syncope and nonsustained ventricular tachycardia and was diagnosed to have hypertrophic obstructive cardiomyopathy. He underwent dual-chamber implantable converter defibrillator (ICD) insertion. Following ICD insertion, in view of some red flags, routine cardiac magnetic resonance imaging was performed, which showed biventricular hypertrophy, diffuse subendocardial gadolinium enhancement of both the ventricles, prolonged T1 and T2, and left ventricular extracellular volume fraction of 50%. A pyrophosphate scan of the heart was strongly positive both at 1 and 3 h intervals. M-band was observed on plasma protein electrophoresis. Serum and urinary immunofixation studies suggested lambda light-chain gammopathy. Multiparametric flow cytometry of the bone marrow aspirate revealed 20% plasma cells immunophenotyped to produce only light-chain immunoglobulins. The patient is on specific chemotherapy for the past 7 months and is asymptomatic.

Role of Multimodality Imaging in the Diagnostic work-up for Cardiac Amyloidosis

Cardiac amyloidosis is caused by the deposition of transthyretin or light-chain fibrils into the myocardium, leading to restrictive cardiomyopathy, and eventually death if untreated. The improvement in diagnostic modalities has seen a recent surge in the number of patients being diagnosed with cardiac amyloidosis, particularly transthyretin amyloidosis. The diagnostic workup often starts with echocardiogram, followed by cardiac magnetic resonance and finally pyrophosphate scintigraphy. It is important to know that while transthyretin amyloidosis is often diagnosed non-invasively with technetium pyrophosphate scan in the contemporary practice, the diagnosis of light-chain amyloidosis still needs tissue confirmation.

Multimodal Imaging Findings Associated With Cardiac Oxalosis Cardiomyopathy

We report the case of a 50-year-old woman with secondary oxalosis following bowel resection resulting in restrictive cardiomyopathy and a diagnosis of cardiac amyloidosis based on the initial workup. The case documented findings by cardiac magnetic resonance imaging and technetium Tc 99m–labeled pyrophosphate scan in patients with cardiac oxalosis, which can mimic findings in cardiac amyloidosis, expanding the differential diagnosis.

Abstract 12473: Majority of Technetium-99m Pyrophosphate Scans for the Evaluation of Transthyretin Cardiac Amyloidosis Are Ordered Without Appropriate Paraprotein Evaluation

Background: Guidelines recommend the use of technetium-99 m pyrophosphate (PYP) scanning after light chain amyloidosis has been ruled out via laboratory testing. Yet lack of execution of this condition significantly hinders the real-world value of PYP scanning to diagnose transthyretin amyloidosis. Objective: The aim of this study was to evaluate the prevalence and consequences of inappropriate PYP scanning at an academic, tertiary care center. Methods: We performed a retrospective study of all PYP scans ordered at our institution from January 2018 to March 2023. Categorical variables were determined as frequencies and percentages. Continuous variables were determined as means and standard deviations. Results: 269 PYP scan orders were identified from 228 distinct patients. Mean age was 67.04 years, 51.2% of patients were female, 66.5% were White, and 47.7% were Hispanic. 52 PYP scans (19.3%) should not have been ordered given positive paraprotein results. 145 PYP scans (53.9%) should not have been ordered given lack of any paraprotein results. Only 9 scans (3.3%) were ordered after negative serum free light chain, serum protein electrophoresis, and serum immunofixation results. Up to seven patients (3.1%) did not receive appropriate paraprotein evaluation prior to tafamidis initiation and thus may have been erroneously treated, representing potential unnecessary healthcare costs to not only the patient, but also the healthcare system. There were no temporal trends for scans performed with zero, three, or positive paraprotein results ( Figure ). Conclusions: Most patients did not undergo complete serum monoclonal protein testing prior to PYP scan ordering. Many patients underwent PYP scanning despite positive serum monoclonal protein test results. Increased awareness and education among physicians regarding paraprotein evaluation prior to PYP scanning is still needed to prevent misdiagnosis, delayed diagnosis, and unnecessary healthcare costs.

Abstract 17577: Cardiomyopathy With Positive ATTR Mutation but Negative Tc-PYP Scan: A Conundrum

Background: Cardiac amyloidosis (CA) is a Hypertrophic Cardiomyopathy (HCM) mimic. Technetium labeled pyrophosphate (Tc-PYP) scan provides a rapid & non-invasive means for identifying ATTR-type CA with 99% sensitivity and specificity. We present 2 patients who were referred to HCM clinic but were found to have genetic testing positive for hTTR. In both cases, Tc-PYP scan was negative. Case Presentation: Outlined in Figure 1. Discussion: Both cases present a diagnostic and management dilemma. Neither of these two patients can be strictly considered asymptomatic carriers of the ATTR gene as both had phenotypic expression in the form of cardiomyopathy & massive LVH on imaging. Yet, in both Tc-PYP scan was negative. Neither had the ATTR mutations (Phe64Leu and Val30Met) that have reported association with negative Tc-PYP scan. Another possibility is early CA, which maybe rarely associated with negative Tc-PYP scan. Patient 1 refused endomyocardial biopsy, so early CA remains on the differential for her. Patient 2 had a negative endomyocardial biopsy. Her case is unique due to history of liver transplant 20 years prior to presentation making phenotypic CA less likely, but not impossible as there have been prior reports of cardiac disease progressing even after liver transplantation in familial ATTR. She also had tacrolimus exposure, which is known to cause LVH in rare cases. Both patients had hypertension, which could have also contributed to LVH. This case series serves to highlight the importance of maintaining a broad differential diagnosis in patients undergoing evaluation for HFpEF and severe LVH, particularly in cases of positive genetic testing but negative PYP scan for CA. From a management standpoint, it is unclear if early initiation of tafamidis might have a role in preventing cardiomyopathy progression in such patients with diagnostic uncertainty & ongoing concern for early CA.

Abstract 16233: Paradoxical Coronary Embolus Associated With Right Atrial Thrombus in Cardiac Amyloidosis

Introduction: This case highlights amyloidosis’ risk for intracardiac thrombosis with an atypical presentation of paradoxical coronary embolism due to right atrial thrombus. Clinical Presentation: An 87-year-old male with atrial fibrillation not on anticoagulation, HFrEF, severe mitral regurgitation, CKD3B, and recent medically managed NSTEMI, presented with shortness of breath. Labs showed elevated Troponin-T HS (174 ng/L) and proBNP (11,955 pg/mL). Echocardiogram revealed EF 25-30% with new lateral and anterior wall akinesis, concerning for NSTEMI I. Coronary catheterization revealed possible thrombus in the left circumflex artery (Figure 1A), but distal perfusion was intact. CT angiogram was negative for coronary artery dissection, providing clearance to initiate treatment with Eliquis. Intriguingly, cardiac MRI suggested intracardiac thrombus within the right atrial appendage and patent foramen ovale (Figure 1B), and possible amyloidosis from delayed gadolinium uptake. Despite negative serologic amyloid workup, pyrophosphate scan confirmed transthyretin amyloidosis. The patient was diuresed for decompensated heart failure but hypotension and acute-on-chronic kidney disease limited Guidelines-Directed Medical Therapy at discharge. Discussion: This case elucidates the importance of recognizing the thromboembolic risk in cardiac amyloidosis patients. Studies indicate up to 30% of cardiac amyloidosis patients have intracardiac thrombi, particularly those with primary amyloidosis subtype. Notably, no correlation exists between the CHA2DS2-VASc score and the presence of left atrial appendage thrombus in patients with cardiac amyloidosis and atrial fibrillation. Despite the left atrial appendage being twice more susceptible to thrombus formation, the right atrial appendage requires attention. Timely screening in high-risk patients could enable early thrombus detection, potentially improving prognosis.

A case of disappearing amyloid on technetium pyrophosphate scan

Technetium-99mm pyrophosphate (Tc-PYP) scintigraphy is a highly accurate non-invasive method for the diagnosis of transthyretin (ATTR) cardiac amyloidosis. Prognosis for this disease is improved following treatment with the transthyretin (TTR) stabilizer tafamidis. Although tafamidis slows disease progression, its effects on myocardial amyloid and Tc-PYP uptake remain unclear. We present a patient with ATTR cardiac amyloidosis who had a strongly positive initial Tc-PYP scan, with a dramatic decrease in Tc-PYP uptake on repeat scan after 3 years of tafamidis treatment. However, myocardial biopsy showed persistent diffuse amyloid deposits. This case highlights the need for further studies regarding the utility of serial Tc-PYP scans in monitoring the progress of ATTR cardiomyopathy.

Prevalence of ATTR-CA and high-risk features to guide testing in patients referred for TAVR.

Transthyretin cardiac amyloidosis (ATTR-CA) is thought to be prevalent in patients with severe aortic stenosis (AS) who are referred for transcatheter aortic valve replacement (TAVR). However, prior studies were published when TAVR was only offered to elderly, inoperable, and high-risk patients. The aim of this study was to reevaluate the prevalence of ATTR-CA in a contemporary TAVR population and identify high-risk features to guide referral for technetium-99 pyrophosphate scan (99mTc-PyP scan) screening. Patients seen in a multidisciplinary TAVR clinic for severe AS 70years and older were referred for a 99mTc-PyP scan to evaluate for ATTR-CA. The primary outcome was the percent with a positive scan. The discriminatory ability of high-risk features was assessed to develop a more judicious screening system. Over the study period, 380 patients underwent screening, and 20 patients (5.3%) had a positive scan, with 17 patients having confirmed ATTR-CA, 1 patient deferring confirmatory testing (combined 4.7%), 1 having light chain amyloidosis, and 1 negative on biopsy. Compared to other patient and echocardiographic measures, elevated NT-pro BNP (> 1000ng/L) was the best discriminator on who should be referred for 99mTc-PyP scan screening, with a sensitivity of 90% and a negative predictive value of 99%. The prevalence of ATTR-CA may be lower in a contemporary TAVR population due to its expanded indication for low-risk patients. NT-pro BNP is a simple test that can improve screening yield and more judiciously guide screening for ATTR-CA in this at-risk population. Comparison of the original versus the proposed algorithm.

Direct comparison of diagnostic and clinical values between Tc-99 m DPD and Tc-99 m PYP scintigraphy in patients with cardiac amyloidosis

BackgroundTechnetium-99 m 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) and technetium-99 m sodium pyrophosphate (PYP) are the two most commonly used radiotracers for cardiac amyloidosis (CA), but no studies have directly compared them. Therefore, in this study, we directly compared the diagnostic and clinical utility of DPD and PYP scintigraphy in patients with CA.MethodsTen patients with CA were enrolled. Eight clinical variables and 12 scintigraphic parameters were used. Clinical variables were age, sex, estimated glomerular filtration rate (eGFR), N-terminal pro brain natriuretic peptide (NT-proBNP), and the results of electromyography (EMG), a sensory test, electrocardiogram, and echocardiography (EchoCG). Four heart retention ratios (heart/whole-body profile, heart/pelvis, heart/skull, and heart/contralateral lung) were calculated from the DPD and PYP scans and two visual scoring systems (Perugini and Dorbala systems) were used. Comparative analyses were performed between radiotracers and between visual scoring systems using clinical variables and scintigraphic parameters.ResultsTwenty DPD parameters and nine PYP parameters had significant associations with age, eGFR, NT-proBNP, EchoCG, and EMG. DPD parameters had more frequent significant associations with clinical variables than PYP parameters. Compared to visual scores in the DPD scan, the proportion of patients with higher visual scores in the PYP scan was relatively greater than those with lower visual scores, and there were more patients with a visual score of 2 or higher in PYP scans than DPD scans.ConclusionsDPD scintigraphy may reflect the disease severity of CA better than PYP scintigraphy, whereas PYP scintigraphy may be a more sensitive imaging modality for identifying CA involvement.

Imaging for implementation of heart failure guidelines.

The classification of heart failure with implications for pharmacological therapeutic interventions rests on defining ejection fraction (EF) which is an imaging parameter. Imaging can provide diagnostic clues as to aetiology of heart failure; it can also guide and help assess response to treatment. Echocardiography, CMR, cardiac computed tomography, positron emission tomography, and Tc 99 m pyrophosphate scanning provide information about the aetiology of heart failure. Further, echocardiography plays the primary role in the evaluation of LV diastolic function and the estimation of left ventricular (LV) filling pressures both at rest and with exercise during diastolic stress testing. Heart failure guidelines recognize four stages (A, B, C, and D) for heart failure. Cardiac imaging along with risk factors and clinical status is needed for identifying these stages. There are joint societal echocardiographic guidelines by American Society of Echocardiography (ASE) of Echocardiography and European Association of Cardiovascular Imaging that are applicable to the imaging of heart failure patients. There are also separate guidelines for the evaluation of patients being considered for LV assist device implantation and for multimodality imaging of patients with heart failure and preserved EF. Cardiac catheterization is needed in patients whose haemodynamic status is uncertain after clinical and echocardiographic evaluation and to evaluate for coronary artery disease. Myocardial biopsy can identify the presence of myocarditis or specific infiltrative diseases when the findings by non-invasive imaging are not conclusive.

Possible gastrointestinal tract involvement in hereditary transthyretin amyloidosis identified by echnitium-99m pyrophosphate scan.

Transthyretin cardiac amyloidosis (ATTR-CA) can be identified through technetium-99m pyrophosphate (Tc-99m PYP) scintigraphy. Gastrointestinal involvement in systemic transthyretin amyloidosis (ATTR-GI) is typically identified through the presence of gastrointestinal symptoms or by screening via endoscopy and/or rectal biopsy. Currently, there is no noninvasive imaging modality for identifying gastrointestinal amyloidosis. In this study, we present a case of a 20-year-old Chinese woman with transthyretin amyloidosis (ATTR) and Phe64Ser mutation. The patient presented with persistent nausea and vomiting, diarrhea and constipation, and poor appetite for 2 years. Tc-99m PYP imaging revealed possible gastrointestinal tract images that coincided with the patient's gastrointestinal symptoms, suggesting the usefulness of Tc-99m PYP scintigraphy as a diagnostic tool for identifying ATTR-GI.

Towards a Diagnosis of Cardiac Amyloidosis: Single Center Experience with 99m Technetium Pyrophosphate Planar Imaging and Opportunities for Standardization of Diagnostic Workflow.

Background and Objectives: Cardiac amyloidosis is a disorder caused by amyloid fibril deposition in the extracellular space of the heart. Almost all forms of clinical cardiac amyloidosis are transthyretin amyloidosis (ATTR) or light chain amyloidosis. 99m technetium pyrophosphate (99mTc PYP scan) has changed the landscape of the non-biopsy diagnosis of ATTR cardiac amyloidosis (ATTR-CA) by providing remarkably high diagnostic accuracy. We examined our experience with PYP scans in patients undergoing workup for ATTR-CA and evaluated the diagnostic workflow in patients with intermediate PYP scan results. Materials and Methods: Retrospective chart review study in which we analyzed data of 84 patients who underwent c-99m pyrophosphate (PYP) SPECT scan for the diagnosis of ATTR-CA from 2017 till 2021 at our institution. We identified three groups: Low uptake (PYPL uptake ratio < 1.2 + visual grade 1/0), n = 30, Intermediate uptake (PYPI uptake ratio 1.2-1.49, visual grade 2/3), n = 25 and High uptake (PYPH uptake ratio ≥ 1.5 + visual grade 2/3), n = 29. We reviewed patients' demographics, medical histories, echo parameters and diagnostic testing including light chain analysis, cardiac magnetic resonance results, and biopsies. Results: Mean patients' age was 73, male-to=female ratio 3:1, 59% of patients were African American. Cardiovascular comorbidities, cardiac biomarkers (BNP and Troponin) and amyloid-related neuropathy were similar in all groups. A statistically significant difference in septal thickness/posterior wall thickness and final diagnosis were found between the groups. The distribution of overall diagnostic testing ratios for the PYPI group included serum protein electrophoresis 92%, urine protein electrophoresis 65%, free light chain 80%, CMR 32%, tissue biopsy done in 20% and BM biopsy in 16%, which are similar to the ratios of other groups. Overall, 25% (n = 5, 4 TTR-CA and 1 AL Amyloid) of patients in the PYPI group had a final diagnosis of CA established with additional testing (p = 0.001 vs. other groups). Conclusions: The 99mPYP scan is an accurate noninvasive test for cardiac ATTR-CA. Importantly, 25% of the PYPI group had a final diagnosis of ATTR-CA reiterating that diagnosis needs to be pursued in PYPI cases based on clinical suspicion. Routine evaluation and exclusion of light chain disease and establishing a consistent workflow for amyloid diagnosis and continued education for technologists and readers of PYP scans is key to a successful amyloidosis workup.

Serum amyloidosis: a cardiac amyloidosis.

A 75-year old male with a history of membranoproliferative glomerulonephritis requiring kidney transplant, carpal tunnel, and peripheral neuropathy presented with new heart failure. An echocardiogram revealed moderate, concentric left ventricular hypertrophy (LVH) despite normal electrocardiographic voltage. To evaluate for the aetiology of unexplained LVH, a cardiac magnetic resonance (CMR) was performed which showed increased wall thickness with markedly increased T1 relaxation time and extensive, near-transmural late gadolinium enhancement throughout the myocardium (Panels A–C, green arrows), findings highly concerning for cardiac amyloidosis (CA). Despite this, a 21.5 mCi Tc-99 m pyrophosphate (Tc-PyP) scan and comprehensive serum (Panels D and E) and urine light chain analysis showed no evidence of transthyretin or immunoglobulin light chain CA, respectively. Despite these negative findings, the patient was referred for endomyocardial biopsy due to high clinical concern for CA. His biopsy revealed diffuse myocardial amyloid deposition (Panels E and F) which was ultimately identified as serum amyloid A (AA) protein on mass spectrometry. AA-CA is a rare form of cardiac amyloidosis caused by deposition of SAA protein—an acute phase reactant—in the myocardium. This disorder is most commonly observed in patients with longstanding chronic inflammatory conditions and is frequently missed by conventional light chain and Tc-PyP analysis. Renal dysfunction is a key feature of AA-CA and is present in a most cases. This case highlights the importance of having a low threshold to pursue further testing including invasive tissue biopsy when typical CA CMR features are present even in the absence of confirmatory non-invasive testing.

Abstract 14476: Automatic Radiomics-Based Assessment of Myocardial Texture in Transthyretin Cardiac Amyloidosis: A 2D Echocardiographic Study

Introduction: Myocardial i nfiltration with amyloid fibrils increases myocardial echogenicity on echocardiography (echo). Increased echogenicity has been challenging to quantify. Radiomics methods may better detect changes in echogenicity than the human eye. Our objectives were (1) to detect an altered myocardial echogenicity in transthyretin cardiac amyloidosis (ATTR-CM) using radiomics analysis and (2) to compare myocardial echogenicity by radiomics to human interpretation. Methods: We evaluated echo images of 515 patients with suspected ATTR-CM referred for an 99m-technetium pyrophosphate scan at 3 major amyloidosis centers. Myocardial echogenicity was assessed at the basal interventricular septum using an open-source radiomics platform (LIFEx) to extract 41 texture-based features. The texture features were processed using a cloud platform (BigML), which performed automated model selection and hyperparameter tuning (Figure). The studies were randomly split into training (80%) and evaluation (20%) sets. Two echo and amyloidosis experts visually evaluated myocardial echogencity on 80 random studies and classified them into ATTR-CM or non- ATTR-CM. Results: In this cohort, 57% of patients were diagnosed with ATTR-CM. The best radiomics model was a decision forest with bootstrapping, with an AUC of 0.79 (95% CI: 0.70-0.88) for diagnosing ATTR-CM. By contrast, visual classification of echo texture as ATTR-CM or not was poor; the interobserver agreement for assessing a septal ROI for altered myocardial echogenicity consistent with ATTR-CM was a kappa of 0.29 and using the entire apical 4 chamber view 0.44. Given the poor agreement an AUC could not be calculated. Conclusions: We have validated the use of a radiomics approach to evaluate myocardial echogenicity in ATTR-CMP. This work lays the foundation to evaluate changes in myocardial texture using echo to raise the suspicion of cardiac amyloidosis and assess changes following targeted TTR therapies.

Abstract 14292: Association of Technetium Pyrophosphate Scan Grade With Adverse Remodeling and Burden in Cardiac Amyloidosis

Introduction: While technetium pyrophosphate (Tc-PyP) is known to be highly accurate for identifying transthyretin cardiac amyloidosis (ATTR-CA), it is currently unclear whether the grade of uptake observed on Tc-PyP correlates with either amyloid burden or adverse cardiac remodeling. Methods: At three academic medical centers, we retrospectively identified patients with confirmed ATTR-CA—defined in accordance with guidelines using either tissue biopsy or grade ≥2 Tc-PyP uptake—who underwent Tc-PyP and cardiac magnetic resonance (CMR) at 1.5T (Phillips, Siemens or GE). Left (LV) and right (RV) ventricular size, mass, and systolic function were quantified. T1 mapping including extracellular volume (ECV)—a surrogate for amyloid burden—was quantified according to guidelines. 3-hour Tc-PyP grade was assessed in accordance with guidelines. CMR markers were correlated with Tc-PyP grade using ANOVA with pair-wise comparisons made using t-test, Wilcoxon rank, or chi-squared as appropriate with p&lt;0.01 used to denote significance. Results: 45 patients were included (mean age 75.4 years, 75.6% male). Within the cohort, grade 0, 1, 2, and 3 uptake were present in 1(2%), 3(7%), 6(13%), and 35(78%) patients respectively. All patients with Tc-PyP grade &lt;2 were confirmed to have ATTR-CA by endomyocardial biopsy. Neither age, gender, or comorbidities differed significantly based on Tc-PyP uptake (Panel A). In univariate analysis, both indexed LV mass and ECV were significantly associated with Tc-PyP grade (Panel B). As compared to those with grade 2, patients with grade 3 Tc-PyP uptake had significantly higher ECV (p&lt;0.001) and indexed LV mass (p=0.003). Conclusions: The presence of higher Tc-PyP grade is associated with increasing amyloid burden and a greater degree of adverse LV remodeling. Higher Tc-PyP grade appears to be indicative of more advanced disease stage in this patient population.

Light Chain Testing Abnormalities Among Patients With Transthyretin Amyloid Cardiomyopathy Referred for Technetium-99m Pyrophosphate Imaging

Clinical algorithms stipulate that transthyretin amyloid cardiomyopathy (ATTR-CM) can be diagnosed noninvasively by technetium-99m pyrophosphate (PYP) imaging when light chain (AL) amyloidosis has been excluded. We sought to define the distribution of light chain abnormalities and final diagnosis of ATTR-CM among patients referred for PYP imaging. We conducted a retrospective cohort study of 378 sequential patients with suspected ATTR-CM, referred for PYP imaging from October 2014 to January 2019. PYP scans were adjudicated as per guidelines. We found that 97 patients (26%) had abnormal plasma cell dyscrasia (PCD) markers, including serum free light chain (FLC) and/or urine/serum immunofixation electrophoresis (IFE). After exclusions for incomplete data or known AL amyloidosis, the final study population with abnormal PCD testing was n=82. Final adjudication of amyloidosis was determined by multidisciplinary clinical assessment and/or tissue biopsy. The median age of cohort was 75 (68 to 81) years, 88% were men, and 33% were Black. Of the 82 patients, 62 had positive PYP scans (76%) and 20 had negative PYP scans (24%). A total of 64 patients had adjudicated ATTR-CM, confirmed by tissue biopsy in 41 (64%). Of those with confirmed ATTR-CM, 44 (69%) had abnormal FLC ratio between 1.65 and 3.1 and normal IFE. In conclusion, among patients referred for technetium-99m-PYP imaging for suspected ATTR-CM, 26% exhibited abnormalities of PCD markers. An FLC ratio 1.65 to 3.1, with normal IFE was noted in 69% of those with ATTR-CM, suggesting that ATTR-CM can be diagnosed noninvasively without cardiac biopsy in patients with positive PYP scan and similar plasma cell testing results.

Hereditary Transthyretin Amyloidosis Cardiomyopathy: The South Florida Experience

Numerous studies have examined distinct populations with hereditary transthyretin amyloidosis (hATTR); however, to the best of our knowledge, no studies have focused on the hATTR population of South Florida, a region characterized by its diverse population, with a prominent Black, Afro-Caribbean, and Hispanic presence. We performed a retrospective observational study of patients diagnosed with hATTR cardiomyopathy from 2010 to 2020 at the University of Miami Hospital located in Miami, Florida. Patients with either a positive endomyocardial biopsy or Technetium-99m Pyrophosphate scan were selected and classified into hATTR or wild-type ATTR (ATTRwt), based on genetic testing results. A subsequent electronic medical record review was performed, and baseline characteristics were obtained for both groups. A total of 144 patients were identified to have ATTR and were included in this study. Of these patients, 36% had hATTR (n=52), and 64% had ATTRwt (n=92). Baseline age, gender, and race characteristics in the hATTR and ATTRwt groups were consistent with previous observational studies. When comparing our findings with preliminary data from the Transthyretin Amyloidosis Outcome Survey reported in 2016, we observed a higher proportion of Val122Ile (75% vs 44% of all hATTR cases), a lower proportion of hATTR cases (36% vs 52%), and a higher proportion of ATTRwt (64% vs 48%). Preliminary data from the Transthyretin Amyloidosis Outcome Survey did not report specific data about Hispanic patients with hATTR, with only 7% of all cases reported being from non-Caucasian and non-Black patients. Hispanic patients represented 25% of all hATTR cases within our population, with 69% of them being positive for the Val122Ile allele. In conclusion, the large presence of Black and Afro-Caribbean subjects within the South Florida region, in combination with its prominent Hispanic population and the high proportion of adults aged more than 65years, results in a unique population composition that could help explain the higher-than-expected frequency of Val122Ile and ATTRwt cases observed within our study.

Beta-Adrenergic Antagonist Tolerance in Amyloid Cardiomyopathy.

Background:Beta-adrenergic antagonists or blockers (BB) are a cornerstone of cardiac therapy for multiple indications. However, BB are considered relatively contraindicated in amyloid cardiomyopathy due to poor tolerance. This intolerance is hypothesized to be due to concomitant neuropathy and significant restrictive cardiomyopathy. This study analyzes the incidence and characteristics of BB tolerance in patients with amyloid cardiomyopathy.MethodsThrough a single-center retrospective chart review, patients with amyloid cardiomyopathy, confirmed by endomyocardial biopsy or technetium-99 pyrophosphate scan, were identified and clinical data was collected. Statistical methods included Chi-square test and two sample t-tests.ResultsOf 135 cardiac amyloidosis patients, 27 patients (20.0%) had no BB use, 56 patients (41.5%) were current BB users, and 52 patients (38.5%) were prior BB users. The most frequent indications for BB use were heart failure, hypertension, coronary artery disease, and arrhythmia. The most common reason for stopping BB therapy was hypotension (62.8%) followed by fatigue, bradycardia, and orthostasis. Neurologic symptoms at the initial BB prescription or most recent evaluation were not significantly different between current and prior BB users. Their cardiovascular profiles were similar by ejection fraction, wall thickness, troponin I, and brain natriuretic peptide. There was no association for BB discontinuation based on amyloid subtype, sex, or race.ConclusionThe majority of patients with amyloid cardiomyopathy were prescribed BB, and over half of these patients still tolerated BB therapy. Current and prior BB users had similar profiles from a cardiovascular and neurologic perspective, with no association identified to predict BB discontinuation.

Relation of Body Mass Index to Transthyretin Cardiac Amyloidosis Particularly in Black and Hispanic Patients (from the SCAN-MP Study)

Heart failure with preserved ejection fraction is a heterogeneous clinical syndrome that includes distinct subtypes with different pathophysiologies, genetics, and treatment. Distinguishing heart failure with preserved ejection fraction caused by transthyretin cardiac amyloidosis (ATTR-CA) is critical given its specific treatment. We analyzed a single-center retrospective cohort to determine the association of body mass index (BMI) with a composite of either ATTR-CA or the valine-to-isoleucine substitution (Val122Ile) variant genotype (ATTR-CA+Val122Ile). These BMI differences were prospectively evaluated in the multicenter Screening for Cardiac Amyloidosis using nuclear imaging for Minority Populations (SCAN-MP) study of Black and Hispanic patients with heart failure. The association of BMI with ATTR-CA+Val122Ile was compared by Wilcoxon rank sum analysis and combined with age, gender, and maximum left ventricle wall thickness in multivariable logistic regression. In the retrospective analysis (n=469), ATTR-CA+Val122Ile was identified in n=198 (40%), who had a lower median BMI (25.8 kg/m2, interquartile range [IQR] 23.4 to 28.9) than other patients (27.1 kg/m2, IQR 23.9 to 32.0) (p <0.001). In multivariable logistic regression, BMI <30 kg/m2 (odds ratio 2.6, 95% confidence interval 1.5 to 4.5) remained independently associated with ATTR-CA+Val122Ile with a greater association in Black and Hispanic patients (odds ratio 5.8, 95% confidence interval 1.7 to 19.6). In SCAN-MP (n=201), 17 (8%) had either ATTR-CA (n=10) or were Val122Ile carriers (n=7) with negative pyrophosphate scans. BMI was lower (25.4 kg/m2 [IQR 24.3 to 28.2]) in ATTR-CA+Val122Ile patients than in non-amyloid patients (32.7 kg/m2 [28.3 to 38.6]) (p <0.001), a finding that persisted in multivariable analysis (p=0.002). In conclusion, lower BMI is associated with ATTR-CA+Val122Ile in heart failure with increased left ventricle wall thickness, particularly in Black and Hispanic patients, and may aid in the identification of those benefiting from ATTR-CA evaluation.

Risk Factors Associated with One Year Mortality from the Time of Cardiac Amyloid Diagnosis

<h3>Purpose</h3> Cardiac amyloidosis (CA) is a form of restrictive cardiomyopathy caused by deposition of immunoglobulin light chains (AL) or misfolded transthyretin (ATTR) in the myocardial interstitium. When diagnosed late, it is associated with increased morbidity and mortality and traditional care pathways when applied to CA patients can be potentially harmful. We thus sought to identify risk factors that predict ≤ 1 year survival after initial diagnosis of CA. <h3>Methods</h3> We performed a single-center, retrospective analysis on patients with CA proven by biopsy or grade 2-3 technetium pyrophosphate scan. Demographic information, clinical parameters, lab results, right heart catheterization numbers, EKG tracings, cardiac imaging parameters (cardiac MRI and echocardiography), and medications were collected. Univariate analysis was performed using the Chi-square test to assess differences in discrete variables and the T-test for continuous variables. The results were analyzed by using SAS JMP pro15. <h3>Results</h3> The 62 CA patients in our cohort were predominantly Caucasian (51.2%) males (87.1%) with a mean age of 72.4 years. Most had ATTR CA (n=48, 77.4% ). Twenty-two (37.4%) patients had at least NYHA class III symptoms at the time of presentation. Overall, 19 (30.6%) died within a year after being diagnosed. Hyponatremia (Na<135, HR 4.21; 95% CI 1.53-11.65), higher brain natriuretic peptide (BNP) levels (≥ 400, HR 4.12; 95% CI 1.17-14.47), higher blood urea nitrogen (BUN) levels (>24, HR 3.45; 95% CI 1.11-10.71), no tafamidis treatment (HR 5.98; 95% CI 1.38-25.91) and impaired left ventricular global longitudinal strain (GLS) on echocardiogram (>-10%, HR 5.24; 95% CI 1.12-24.52) were significant predictors for increased 1-year mortality on univariate analysis. <h3>Conclusion</h3> In our cohort of patients, hyponatremia, elevated BNP, BUN, marked impairment LV GLS (but not LVEF), and not being on tafamidis (for ATTR patients) are risk factors associated with ≤ 1 year survival from the time of cardiac amyloidosis diagnosis.