Assessment Of Cardiac Amyloidosis Research Articles

Multimodality Imaging in the Diagnosis and Assessment of Cardiac Amyloidosis.

Amyloidosis is a rare disorder where abnormal protein aggregates are deposited in tissues forming amyloid fibrils, leading to progressive organ failure. Although any organ can be affected, cardiac involvement is the main cause of morbidity and mortality associated with amyloidosis as diagnosis is often delayed due to the indolent nature of the disease in some forms. An early diagnosis of disease and knowledge of the type/subtype of cardiac amyloidosis (CA) are essential for appropriate management and better outcome. Echocardiography is often the first line of investigation for patients suspected of CA and offers superior hemodynamic assessment. Although cardiovascular magnetic resonance (CMR) imaging is not diagnostic of CA, it provides vital clues to diagnosis and has a role in disease quantification and prognostication. Radiolabeled bone seeking tracers are the mainstay of diagnosis of CA and when combined with screening of monoclonal light chains, bone scintigraphy offers high sensitivity in diagnosing transthyretin type of CA. This review aims to describe the noninvasive imaging assessment and approach to diagnosis of patients with suspected CA. Imaging features of echocardiography, nuclear scintigraphy, and CMR are described with a brief mention on computed tomography.

Assessment of cardiac amyloidosis with 99mTc-pyrophosphate (PYP) quantitative SPECT

Background99mTc-PYP scintigraphy provides differential diagnosis of ATTR cardiomyopathy (ATTR-CM) from light chain cardiac amyloidosis and other myocardial disorders without biopsy. This study was aimed to assess the diagnostic feasibility and the operator reproducibility of 99mTc-PYP quantitative SPECT.MethodThirty-seven consecutive patients who underwent a 99mTc-PYP thorax planar scan followed by SPECT and CT scans to diagnose suspected ATTR-CM were enrolled. For the quantitative SPECT, phantom studies were initially performed to determine the image conversion factor (ICF) and partial volume correction (PVC) factor to recover 99mTc-PYP activity concentration in the myocardium for calculating the standardized uptake value (SUV) (unit: g/ml). SUVmax was compared among groups of ATTR-CM, AL cardiac amyloidosis, and other pathogens (others) and among categories of Perugini visual scores (grades 0–3). The intra- and inter-operator reproducibility of quantitative SPECT was verified, and the corresponded repeatability coefficient (RPC) was calculated.ResultsThe ICF was 79,327 Bq/ml to convert count rate in pixel to 99mTc activity concentration. PVC factor as a function of the measured activity concentration ratio in the myocardium and blood-pool was [y = 1.424 × (1 − exp(− 0.759 × x)) + 0.104]. SUVmax of ATTR-CM (7.50 ± 2.68) was significantly higher than those of AL (1.96 ± 0.35) and others (2.00 ± 0.74) (all p < 0.05). SUVmax of grade 3 (8.95 ± 1.89) and grade 2 (4.71 ± 0.23) were also significantly higher than those of grade 1 (1.92 ± 0.31) and grade 0 (1.59 ± 0.39) (all p < 0.05). Correlation coefficient (R2) of SUVmax reached 0.966 to 0.978 with only small systematic difference (intra = − 0.14; inter = − 0.23) between two repeated measurements. Intra- and inter-operator RPCs were 0.688 and 0.877.Conclusions99mTc-PYP quantitative SPECT integrated with adjustable PVC factors is feasible to quantitatively and objectively assess the burden of cardiac amyloidosis for diagnosis of ATTR-CM.

Multi-modality imaging of cardiac amyloidosis: Contemporary update.

Cardiac amyloidosis is a heterogeneous and challenging diagnostic disease with poor prognosis that is now being altered by introduction of new therapies. Echocardiography remains the first-line imaging tool, and when disease is suspected on echocardiography, cardiac magnetic resonance imaging and nuclear imaging play critical roles in the non-invasive diagnosis and evaluation of cardiac amyloidosis. Advances in multi-modality cardiac imaging allowing earlier diagnosis and initiation of novel therapies have significantly improved the outcomes in these patients. Cardiac imaging also plays important roles in the risk stratification of patients presenting with cardiac amyloidosis. In the current review, we provide a clinical and imaging focused update, and importantly outline the imaging protocols, diagnostic and prognostic utility of multimodality cardiac imaging in the assessment of cardiac amyloidosis.

The Role of Molecular Imaging in the Assessment of Cardiac Amyloidosis: State-of-the-Art.

Cardiac amyloidosis is a progressive infiltrative disease for which new treatments are now available. As therapy should be started as early as possible to avoid complications such as restrictive cardiomyopathy, arrhythmias and heart failure, a prompt and reliable diagnosis by means of non-invasive tests would be highly warranted. Electrocardiography, echocardiography and cardiac magnetic resonance imaging are all used in the evaluation of cardiac amyloidosis with varying diagnostic and prognostic accuracy, but none of these modalities can effectively differentiate the cardiac amyloid subtypes. We aim to highlight the most relevant findings in the literature of molecular imaging in the assessment of patients with cardiac amyloidosis and to underline future clinical perspective. We performed multiple searches using Pub-Med databases in order to find important original articles on the role of molecular imaging in the assessment of patients affected by CA. Several search terms were used, such as "cardiac amyloidosis"; "Light-chain amyloidosis"; "Transthyretin amyloid cardiomyopathy"; "bone scintigraphy"; "single photon emission tomography" or "SPECT"; "Positron emission tomography or PET", and "cardiac imaging". All radiopharmaceuticals tracing cardiac amyloidosis were also included. Several studies about the role of SPECT with bone-seeking tracer (47 articles) and innervation tracer (9 articles) in the work-up of CA, as well as new PET amyloid-binding (14 articles) and bone radiotracer (4 articles) have been reviewed and discussed. Molecular imaging represents a sensitive tool for early assessment of both amyloid burden and cardiac innervation, to differentiate between subtypes and to monitor disease burden, disease progression, and potential response to therapy.

The Evolving Role of Cardiovascular Magnetic Resonance Imaging in the Evaluation of Systemic Amyloidosis.

Systemic amyloidosis is a serious multiorgan disease with reduced life expectancy, irrespective of type. The impact of magnetic resonance imaging (MRI) in managing this condition has been immense. The last decade in particular has seen a surge of interest in the assessment and evaluation of the heart in patients with systemic amyloidosis by cardiovascular magnetic resonance imaging (CMR), with approximately 85% of all publications on this subject arising in the last 10 years. This has been largely driven by the creation of new sequences and their subsequent modernisation and technical development, thereby rendering previously prohibitive methods clinically more relevant and applicable. In turn, this has led to an increased awareness and recognition of the disease. This review demonstrates how MRI has become a pivotal diagnostic tool in the assessment of cardiac amyloidosis over the last 2 decades, with the ability to track disease and predict mortality. Several different pathognomonic patterns of late gadolinium enhancement (LGE) are now recognised and are able to prognosticate. T1 mapping and extracellular volume (ECV) techniques have resulted in even earlier disease detection before LGE is even visible and along with T2 mapping, provide new insights into biology. As newer therapies also evolve and become available, the need for accurate tracking of cardiac disease response to treatment carries increasing importance. All these are examined in this review, mainly focussing on light-chain (AL) and transthyretin (ATTR) amyloidosis.

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)

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.

New tools to diagnose and follow FAC patients: biomarkers

In the last decade, the availability of the cardiac biomarkers N terminal pro-natriuretic peptide type-B (NT-proBNP) and troponins has radically changed the approach to diagnosis, staging, and response assessment of cardiac amyloidosis. Despite similar appearance at standard imaging, the main types of amyloidosis involving the heart are characterized by different rates of progression and different outcomes. In general, patients with ATTRm amyloidosis have lower concentrations of cardiac biomarkers and usually a better prognosis than subjects suffering from AL amyloidosis. Nevertheless, the clinical manifestations of ATTRm amyloidosis are heterogeneous. Different amyloidogenic TTR mutations give rise to different cardiac phenotypes, ranging from exclusively neuropathic diseases, through mixed phenotypes, to mutation characterized by severe cardiac dysfunction. For instance, one of the mutations associated with cardiac involvement in ATTRm amyloidosis, Ile68Leu, presents with high NT-proBNP concentrations, comparable to those observed in patients with cardiac AL amyloidosis. In our series, survival of patients with Ile68Leu ATTRm is not different from that of cardiac AL patients. Thus, it is possible that NT-proBNP represents a viable marker for early diagnosis of cardiac involvement in ATTR patients with “aggressive” mutations. This marker could be considered in the screening of carriers of these mutations. Despite the lack of systematic studies of cardiac biomarkers in ATTR amyloidosis, the results of several small published series and the analysis of the Pavia patient population, indicate that NT-proBNP and cardiac troponins have prognostic value in this disease, correlating to amyloid burden and adding to known prognostic factors. The availability of several novel therapeutic options for ATTRm, require objective means for the assessment of treatment efficacy in routine clinical practice and in clinical trials. Early results from the Pavia series indicate that NT-proBNP progression portends a poor prognosis, and cardiac biomarkers will probably find their place in the evaluation of response to therapy in ATTRm amyloidosis. Cardiac biomarkers will most likely become increasingly useful in the management of patients with ATTRm amyloidosis in the near future. However, studies of biomarkers in this disease are hindered by small numbers and disease heterogeneity. Prospective studies and international collaboration are warranted to define the role of cardiac biomarkers in the diagnosis and follow-up of cardiac ATTRm amyloidosis.

Regionally heterogeneous tissue mechanics in cardiac amyloidosis

Objective. The goal of this study was to examine in vitro tissue stiffness and contractile performance in myocardial amyloidosis.Background. Primary systemic amyloidosis involves the deposition of amyloid protein in mesodermal tissues including the heart. Functional assessment of cardiac amyloidosis is usually performed using echocardiography. However, this technique does not involve assessment of preload-dependent contractile reserve (the Frank-Starling mechanism).Methods. At the time of heart transplantation, isolated myocardial trabeculae were dissected from the right ventricle of a patient with primary systemic amyloidosis. In vitro length-tension experiments were performed and trabeculae were subsequently fixed, sectioned and stained with crystal violet to determine amyloid deposition.Results. Among the nine trabeculae capable of generating force transients, various combinations of myocardial stiffness and contractile performance were observed including normal stiffness and contractility, severely increased stiffness with impaired contractility and hybrid patterns. Histological analysis demonstrated varying degrees of amyloid deposition among sampled trabeculae.Conclusions. Our findings extend previous reports of functional heterogeneity among patients by demonstrating functional heterogeneity within a single patient's heart. Our findings also highlight the functional interdependence of passive stiffness and systolic performance in the diseased myocardium and demonstrate the value of dynamic assessments of myocardial performance.