An Autopsy Case of Cardiac Amyloidosis with Heterogeneous Deposition of Amyloid Protein: A Possible Mechanism for Relative Apical Sparing of Longitudinal Strain.
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SUBMITTER: Sawada N
PROVIDER: S-EPMC7175792 | biostudies-literature | 2020 Apr
REPOSITORIES: biostudies-literature
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Project description:Cardiac amyloidosis (CA) is an infiltrative disease. In the present study, we compared the diagnostic accuracy of cardiovascular magnetic resonance (CMR)-based T1-mapping and subsequent extracellular volume fraction (ECV) measurement and longitudinal strain analysis in the same patients with (a) biopsy-proven cardiac amyloidosis (CA) and (b) hypertrophic cardiomyopathy (HCM). N = 30 patients with CA, N = 20 patients with HCM and N = 15 healthy control patients without relevant cardiac disease underwent dedicated CMR studies. The CMR protocol included standard sequences for cine-imaging, native and post-contrast T1-mapping and late-gadolinium-enhancement. ECV measurements were based on pre- and post-contrast T1-mapping images. Feature-tracking analysis was used to calculate 3D left ventricular longitudinal strain (LV-LS) in basal, mid and apical short-axis cine-images and to assess the presence of relative apical sparing. Receiver-operating-characteristic analysis revealed an area-under-the-curve regarding the differentiation of CA from HCM of 0.984 for native T1-mapping (p < 0.001), of 0.985 for ECV (p < 0.001) and only 0.740 for the "apical-to-(basal + midventricular)"-ratio of LV-LS (p = 0.012). A multivariable logistical regression analysis showed that ECV was the only statistically significant predictor of CA when compared to the parameter LV-LS or to the parameter "apical-to-(basal + midventricular)" LV-RLS-ratio. Native T1-mapping and ECV measurement are both superior to longitudinal strain measurement (with assessment of relative apical sparing) regarding the appropriate diagnosis of CA.
| S-EPMC8324782 | biostudies-literature
Project description:BackgroundCardiac amyloidosis (CA) mimics left ventricular hypertrophy (LVH). It is treatable, but its prognosis is poor. A simple screening tool for CA would be valuable. CA is more precisely diagnosed with echocardiographic deformation parameters (e.g., relative apical sparing pattern [RASP]) than with conventional parameters. We aimed to 1) investigate incremental benefits of echocardiographic deformation parameters over established parameters for CA screening; 2) determine the resultant risk score for CA screening; and 3) externally validate the score in LVH patients.MethodsWe retrospectively studied 295 consecutive non-ischemic LVH patients who underwent detailed diagnostic tests. CA was diagnosed with biopsy or 99mTc-PYP scintigraphy. The base model comprised age (≥65 years [men], ≥70 years [women]), low voltage on the electrocardiogram, and posterior wall thickness ≥ 14 mm in reference to the literature. The incremental benefit of each binarized echocardiographic parameter over the base model was assessed using receiver operating characteristic curve analysis and comparisons of the area under the curve (AUC).ResultsFifty-four (18%) patients had CA. RASP showed the most incremental benefit for CA screening over the base model. After conducting multiple logistic regression analysis for CA screening using four variables (RASP and base model components), a score was determined (range, 0-4 points). The score demonstrated adequate discrimination ability for CA (AUC = 0.86). This result was confirmed in another validation cohort (178 patients, AUC = 0.88).ConclusionsWe developed a score incorporating RASP for CA screening. This score is potentially useful in the risk stratification and management of LVH patients.
| S-EPMC8383373 | biostudies-literature
Project description:OBJECTIVES:This study sought to test whether relative apical sparing (RELAPS) of left ventricular (LV) longitudinal strain (LS) in cardiac amyloidosis (CA) is explained by regional differences in markers of amyloid burden (18F-florbetapir uptake by positron emission tomography [PET] and/or extracellular volume fraction [ECV] by cardiac magnetic resonance (CMR)]. BACKGROUND:Further knowledge of the pathophysiological basis for RELAPS can help understand the adverse outcomes associated with apical LS impairment. METHODS:This was a prospective study of 32 subjects (age 62 ± 7 years; 50% males) with light chain CA. All subjects underwent two-dimensional echocardiography for LS estimation and 18F-florbetapir PET for quantification of LV florbetapir retention index (RI). A subset also underwent CMR (n = 22) for ECV quantification. Extracellular LV mass (LV mass*ECV) and total florbetapir binding (extracellular LV mass*florbetapir RI) were also calculated. All parameters were measured globally and regionally (base, mid, and apex). RESULTS:There was a significant base-to-apex gradient in LS (-7.4 ± 3.2% vs. -8.6 ± 4.0% vs. -20.8 ± 6.6%; p < 0.0001), maximal LV wall thickness (15.7 ± 1.9 cm vs. 15.4 ± 2.9 cm vs. 10.1 ± 2.4 cm; p < 0.0001), and LV mass (74.8 ± 21.2 g vs. 60.8 ± 17.3 g vs. 23.4 ± 6.2 g; p < 0.0001). In contrast, florbetapir RI (0.089 ± 0.03 ?mol/min/g vs. 0.097 ± 0.03 ?mol/min/g vs. 0.085 ± 0.03 ?mol/min/g; p = 0.45) and ECV (0.53 ± 0.08 vs. 0.49 ± 0.08 vs. 0.49 ± 0.07; p = 0.15) showed no significant base-to-apex gradient in the tissue concentration or proportion of amyloid infiltration, whereas markers of total amyloid load, such as total florbetapir binding (3.4 ± 1.7 ?mol/min vs. 2.8 ± 1.5 ?mol/min vs. 0.93 ± 0.49 ?mol/min; p < 0.0001) and extracellular LV mass (40.0 ± 15.6 g vs. 30.2 ± 10.9 g vs. 11.6 ± 3.9 g; p < 0.0001), did show a marked base-to-apex gradient. CONCLUSIONS:Segmental differences in the distribution of the total amyloid mass, rather than the proportion of amyloid deposits, appear to explain the marked regional differences in LS in CA. Although these 2 matrices are clearly related concepts, they should not be used interchangeably.
| S-EPMC6377347 | biostudies-literature
Project description:Backgrounds:The relative apical sparing pattern (RASP) of left ventricular (LV) longitudinal strain (LS) is frequently associated with cardiac amyloidosis. Elderly patients with aortic valve stenosis (AS) complicated by transthyretin amyloid cardiomyopathy have poor prognosis. Furthermore, deteriorated basal LS in AS patients has been reported to be associated with adverse outcome. We investigated the association between RASP and outcomes in patients with severe AS. Methods:We retrospectively studied 156 consecutive patients with severe AS and preserved LV ejection fraction. RASP was assessed by both of semi-quantitative (sRASP) and quantitative (qRASP) methods. sRASP was defined as a deterioration of LS (?-10%) in ? 5 (of 6) basal segments, relative to preserved LS (<-15%) in at least 1 apical segment. qRASP was calculated using the following formula: average apical LS/(average basal LS + average mid-ventricle LS); qRASP ? 1 was defined as positive. Patients were followed up to determine outcomes, which included sudden cardiac death or unexpected admission due to heart failure, over a median of 1.9 years. Results:sRASP and qRASP were assessed in all patients, but 24 and 42 patients fulfilled the criteria for sRASP and qRASP, respectively. Both assessments were significantly associated with outcomes (n = 44; 28%). Furthermore, sRASP was significantly associated with outcome after adjusting for EuroSCORE, NYHA ? II, or global longitudinal strain. A model based on these covariates for predicting outcomes significantly improved by adding sRASP. Conclusion:RASP is observed in some patients with severe AS and provides additive prognostic information over conventional parameters.
| S-EPMC7280361 | biostudies-literature
Project description:AimsThe accuracy of an apical-sparing strain pattern on transthoracic echocardiography (TTE) for predicting cardiac amyloidosis (CA) has varied in prior studies depending on the underlying cohort. We sought to evaluate the performance of apical sparing and other TTE strain findings to screen for CA in an unselected population and determine the frequency that patients with echocardiographic concern for CA undergo evaluation for amyloidosis in clinical practice.Methods and resultsAs strain is routinely performed at our institution on all clinical TTEs, we identified all TTEs performed from 2016 through 2019 with reported concern for CA or apical sparing. We determined the performance characteristics for echocardiographic strain findings in discriminating CA including apical sparing, the ejection fraction to global longitudinal strain ratio (EF/GLS), and the septal apical-septal basal ratio (SA/SB); other clinical predictors of confirmed CA; and predictors of patients who underwent complete evaluation for CA. CA was confirmed by endomyocardial biopsy or diagnostic cardiac imaging. A total of 547 TTEs, representing 451 patients, reported concern for CA and had adequate strain for analysis. A total of 111 patients underwent complete evaluation for amyloidosis with 100 patients undergoing complete cardiac evaluation for CA. In those 100 patients, multivariable predictors of confirmed CA were age [odds ratio (OR) 3.37 per 5 years], a visual apical-sparing pattern (OR 10.85), and left ventricular ejection fraction (LVEF)/GLS > 4.1 (OR 35.37). CA was less likely in those with coronary artery disease (OR 0.04), hypertension (OR 0.18), and increased systolic blood pressure (OR 0.60 per 5 mm Hg increase). SA/SB [area under the curve (AUC) 0.72, 95% confidence interval (CI) 0.60-0.84] and LVEF/GLS (AUC 0.72, 95% CI 0.60-0.84) both had improved discrimination for CA compared with the apical-sparing ratio (AUC 0.66, 95% CI 0.54-0.79). Many patients with suggestive TTE findings did not receive an evaluation for amyloidosis. Complete evaluation was more likely with Caucasian race (OR 2.1), increased septal thickness (OR 1.4), increased body mass index (OR 1.2), and if the report specifically stated 'amyloid' (OR 1.9). Evaluations were less likely in patients with comorbidities. While hypertension reduced the likelihood of evaluating for CA, 34% of patients with CA had hypertension (>130/80 mm Hg) at time of diagnosis.ConclusionsIn a broad population of patients undergoing TTE, apical sparing on strain imaging increased the likelihood of CA diagnosis but with modest sensitivity and specificity. GLS/EF ratio may be a more reliable tool to screen for CA. The low rate of complete evaluation in patients with concerning TTE findings indicates a strong need for practice improvement and enhanced disease awareness.
| S-EPMC8788049 | biostudies-literature
Project description:AimThis study was conducted to investigate the meaning of left ventricular (LV) apical sparing in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM).Methods and results165 patients who were diagnosed with ATTRwt-CM at Kumamoto University Hospital from January 2002 to December 2020 and had sufficient data for two-dimensional speckle tracking echocardiography were enrolled. Of these, 86 patients (52 %) had LV apical sparing (relative apical longitudinal strain index (RapLSI) > 1.0). Multivariable logistic regression analysis revealed the following variables were significantly associated with LV apical sparing: interventricular septal thickness in diastole (odds ratio (OR), 1.19; 95 % confidence interval (CI), 1.01-1.41; p < 0.05); E/e' ratio (OR, 1.06; 95 % CI, 1.00-1.11; p < 0.05); and heart-to-contralateral ratio by 99mTc-labeled pyrophosphate scintigraphy (OR, 3.40; 95 % CI, 1.07-10.83; p < 0.05).Next, we compared RapLSI at the time of diagnosis with that during the follow-up period (396 days (346-458) after diagnosis) in 92 patients. RapLSI increased significantly during the follow-up period compared with RapLSI at diagnosis in the non-LV apical sparing group (0.89 ± 0.32 vs 0.74 ± 0.18, p < 0.01) but not in the LV apical sparing group (1.33 ± 0.53 vs 1.39 ± 0.45, p = 0.46). A total of 12 patients (29 %) in the non-LV apical sparing group developed LV apical sparing and 11 patients (22 %) in LV apical sparing group diminished LV apical sparing during the follow-up period.ConclusionApproximately half of ATTRwt-CM patients did not have LV apical sparing at diagnosis. Because RapLSI in ATTRwt-CM significantly changed over time, repeated two-dimensional speckle tracking analysis is important for suspected ATTR-CM patients.
| S-EPMC9643881 | biostudies-literature
Project description:BackgroundThe commonly used methods for amyloid typing include immunofluorescence or immunohistochemistry (IHC), which sometimes may come with diagnostic pitfalls. Mass spectrometry (MS)-based proteomics has been recognized as a reliable technique in amyloid typing.Case presentationWe reported two middle-aged patients who presented with proteinuria, hypertension and normal renal function, and both had a family history of renal diseases. The renal biopsies of both patients revealed renal amyloidosis with the similar pattern by massive exclusively glomerular amyloid deposition. The IHC was performed by using a panel of antibodies against the common types of systemic amyloidosis, and demonstrated co-deposition of fibrinogen Aα chain and apolipoprotein A-I in the glomerular amyloid deposits of each patient. Then the MS on amyloid deposits captured by laser microdissection (LMD/MS) and genetic study of gene mutations were investigated. The large spectra corresponding to ApoA-I in case 1, and fibrinogen Aα chain in case 2 were identified by LMD/MS respectively. Further analysis of genomic DNA mutations demonstrated a heterozygous mutation of p. Trp74Arg in ApoA-I in case 1, and a heterozygous mutation of p. Arg547GlyfsTer21 in fibrinogen Aα chain in case 2.ConclusionsThe current study revealed that IHC was not reliable for accurate amyloid typing, and that MS-based proteomics and genetic analysis were essential for typing of hereditary amyloidosis.
| S-EPMC6929319 | biostudies-literature
Project description:ObjectivesThe aim of this study was to train and validate deep learning algorithms to quantitate relative amyloid deposition (RAD; mean amyloid deposited area per stromal area) in corneal sections from patients with familial amyloidosis, Finnish (FAF), and assess its relationship with visual acuity.MethodsCorneal specimens were obtained from 42 patients undergoing penetrating keratoplasty, stained with Congo red, and digitally scanned. Areas of amyloid deposits and areas of stromal tissue were labeled on a pixel level for training and validation. The algorithms were used to quantify RAD in each cornea, and the association of RAD with visual acuity was assessed.ResultsIn the validation of the amyloid area classification, sensitivity was 86%, specificity 92%, and F-score 81. For corneal stromal area classification, sensitivity was 74%, specificity 82%, and F-score 73. There was insufficient evidence to demonstrate correlation (Spearman's rank correlation, -0.264, p = 0.091) between RAD and visual acuity (logMAR).ConclusionsDeep learning algorithms can achieve a high sensitivity and specificity in pixel-level classification of amyloid and corneal stromal area. Further modeling and development of algorithms to assess earlier stages of deposition from clinical images is necessary to better assess the correlation between amyloid deposition and visual acuity. The method might be applied to corneal dystrophies as well.
| S-EPMC6984152 | biostudies-literature
Project description:Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) population, we examined (1) cross-sectional relationships between amyloid deposition, hypometabolism, and cognition, and (2) associations between amyloid and hypometabolism measurements and longitudinal cognitive measurements.We examined associations between mean cortical florbetapir uptake, mean (18) F-fluorodeoxyglucose-positron emission tomography (FDG-PET) within a set of predefined regions, and Alzhiemer's Disease Assessment Scale (ADAS-cog) performance in 426 ADNI participants (126 normal, 162 early mild cognitive impairment [EMCI], 85 late MCI [LMCI], 53 Alzheimer disease [AD] patients). For a subset of these (76 normal, 81 LMCI) we determined whether florbetapir and FDG-PET were associated with retrospective decline in longitudinal ADAS-cog measurements.Twenty-nine percent of normal subjects, 43% of EMCI patients, 62% of LMCI patients, and 77% of AD patients were categorized as florbetapir positive. Florbetapir was negatively associated with concurrent FDG and ADAS-cog in both MCI groups. In longitudinal analyses, florbetapir-positive subjects in both normal and LMCI groups had greater ongoing ADAS-cog decline than those who were florbetapir negative. However, in normal subjects, florbetapir positivity was associated with greater ADAS-cog decline than FDG, whereas in LMCI, FDG positivity was associated with greater decline than florbetapir.Although both hypometabolism and ?-amyloid (A?) deposition are detectable in normal subjects and all diagnostic groups, A? showed greater associations with cognitive decline in normal participants. In view of the minimal cognitive deterioration overall in this group, this suggests that amyloid deposition has an early and subclinical impact on cognition that precedes metabolic changes. At moderate and later stages of disease (LMCI/AD), hypometabolism becomes more pronounced and more closely linked to ongoing cognitive decline.
| S-EPMC3786871 | biostudies-literature
Project description:Cardiac ATTR amyloidosis, a serious but much under-diagnosed form of cardiomyopathy, is caused by deposition of amyloid fibrils derived from the plasma protein transthyretin (TTR), but its pathogenesis is poorly understood and informative in vivo models have proved elusive. Here we report the generation of a mouse model of cardiac ATTR amyloidosis with transgenic expression of human TTRS52P. The model is characterised by substantial ATTR amyloid deposits in the heart and tongue. The amyloid fibrils contain both full-length human TTR protomers and the residue 49-127 cleavage fragment which are present in ATTR amyloidosis patients. Urokinase-type plasminogen activator (uPA) and plasmin are abundant within the cardiac and lingual amyloid deposits, which contain marked serine protease activity; knockout of α2-antiplasmin, the physiological inhibitor of plasmin, enhances amyloid formation. Together, these findings indicate that cardiac ATTR amyloid deposition involves local uPA-mediated generation of plasmin and cleavage of TTR, consistent with the previously described mechano-enzymatic hypothesis for cardiac ATTR amyloid formation. This experimental model of ATTR cardiomyopathy has potential to allow further investigations of the factors that influence human ATTR amyloid deposition and the development of new treatments.
| S-EPMC8651690 | biostudies-literature