Hepatic and cardiac shear wave elastography in the assessment of hereditary transthyretin amyloidosis

Donato, Glaudir; de Medeiros Filho, José Eymard Moraes; Melo, Marcelo

doi:10.1016/j.medcli.2023.10.019

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(A and B) Parasternal long and short axis disclosing the classical cardiac amyloidosis features: increased myocardial thickness, pericardial effusion, valve thickening; (C) Bulls’ eye showing a very reduced global longitudinal strain (8.8%) with apical sparing (the worse deformation regions corresponding with basal ones); (D) Hepatic elastography, 78.9kPa in a segment at right hepatic lobe; (E) Cardiac elastography in the basal cardiac septum (2.36kPa); (F) Cardiac elastography in the apical region showing less stiffness comparing to basal regions (0.62kPa). AO: aorta; LA: left atrium; LV: left ventricle; RV: right ventricle. White arrows: regions of interest of the shear wave elastography technique; red arrow: mitral valve thickening; white asterisks: pericardial effusion; red asterisks: increased myocardial thickness." ] ] ] "textoCompleto" => "Hereditary transthyretin amyloidosis (ATTRv) is a rare autosomal dominant disease with insidious and often fatal progression. Transthyretin (TTR) mutations cause insoluble β-sheet fibril aggregates, which are then deposited in various tissues. Nervous tissue involvement leads to peripheral neuropathy, while cardiac deposition results in heart failure (HF), defining hallmarks of the disease.<a class="elsevierStyleCrossRef" href="#bib0030">1</a>Cardiac amyloidosis stiffens myocardium, progressing to restrictive cardiomyopathy in advanced stages. Multimodal imaging facilitates earlier disease recognition, sometimes enabling non-invasive diagnosis. However, non-invasive hemodynamic assessments indirectly estimate cardiac filling pressures, facing potential technical and diagnostic limitations.<a class="elsevierStyleCrossRef" href="#bib0035">2</a>We report the case of an elderly South American male who developed progressive peripheral neuropathy, initially affecting the lower limbs, and subsequently extending to the hands. Over approximately a decade, this condition evolved into a sensorimotor deficit, impairing writing and walking. At the age of 70, he presented with exertional dyspnea, lower limb edema and refractory ascites, requiring repeated paracenteses.Upon cardiological evaluation, he was classified as New York Heart Association functional class III, frequently decompensating to class IV, despite optimized therapy for severe HF. Echocardiographic findings suggested infiltrative cardiomyopathy (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>, A–C), prompting suspicion of cardiac amyloidosis. In January 2020, molecular analysis of TTR gene identified the p.Val142Ile variant.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>In July 2020, upper abdominal ultrasound, and hepatic shear wave elastography (SWE) were performed to investigate possible concomitant chronic liver disease. The imaging showed a liver with uniform echotexture, well-defined margins, slightly attenuated edges, and increased stiffness (median 41.42kPa, SD 14.84kPa); besides, liver function was normal in serum test. A week later, the same hepatic SWE method was applied for cardiac stiffness assessment, revealing higher stiffness at the base (2.36kPa) compared to the apex (0.6kPa to 0.62kPa) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>, D–F).In the case discussed, the ATTRv hypothesis arose due to a concurrent neurological condition and, notably, refractory HF, which ultimately led to patient's death three months later. Another noteworthy clinical aspect was severe congestion, which instigated the utilization of hepatic SWE to explore differential diagnoses and hepatic stiffness secondary to passive congestion.This technique is commonly employed to assess hepatic fibrosis, such as in cirrhosis, with stiffness values increasing in concordance with fibrosis stage. For instance, Dhyani et al. (2017) reported median SWE values ranging from 6.93kPa for stage F0 to 23.73kPa for stage F4.<a class="elsevierStyleCrossRef" href="#bib0040">3</a> Similarly, in chronic HF, studies indicate a gradual increase in hepatic SWE values corresponding to disease stage. For example, Nakayama et al. (2021) identified an average hepatic SWE value of 17.7±12.7kPa in patients with stage D HF according to the American College of Cardiology Foundation/American Heart Association criteria.<a class="elsevierStyleCrossRef" href="#bib0045">4</a>Given the hepatic SWE results and the lack of laboratory evidence of chronic liver disease, the increase in liver stiffness may be better explained by amyloid deposition in the reported case. Even with the influence of passive congestion due to right HF, the SWE values far exceed those described in the literature. This line of reasoning is supported by the fact that amyloidosis often affects the liver, but rarely leads to secondary liver failure. Moreover, the liver is the main site of TTR production.<a class="elsevierStyleCrossRef" href="#bib0030">1</a> In a similar vein to what was observed, Trifanov et al. (2015) reported a case of light-chain amyloidosis involving elevated hepatic stiffness with a median value of 99.1kPa.<a class="elsevierStyleCrossRef" href="#bib0050">5</a> Nevertheless, this paper marks the first description of liver stiffness using SWE in ATTRv.Various imaging methods for amyloidosis-related cardiomyopathy emphasize basal cardiac involvement, sparing the apex.<a class="elsevierStyleCrossRef" href="#bib0030">1</a> Recently, cardiac stiffness assessment via natural shear wave imaging has shown promise in diagnosing diastolic dysfunction and infiltrative cardiomyopathies, indicating higher shear wave velocities in cardiac amyloidosis. However, this relies on indirect methods like ultrafast echocardiography to estimate myocardial stiffness.<a class="elsevierStyleCrossRef" href="#bib0035">2</a>A distinguishing aspect of this case is the application of hepatic SWE to evaluate ATTRv-related cardiomyopathy. This approach directly gauges cardiac stiffness and offers the first description of this technique. It aligns with existing literature by illustrating pronounced amyloid deposition in basal regions compared to apical segments. Further studies are needed to confirm the role of prognostic stratification and therapeutic monitoring of cardiac amyloidosis applying this new approach.Ethical considerationsThe approval of scientific committee was not required for this paper.FundingThis article did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Conflicts of interestThe authors declare no conflict of interest." 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(A and B) Parasternal long and short axis disclosing the classical cardiac amyloidosis features: increased myocardial thickness, pericardial effusion, valve thickening; (C) Bulls’ eye showing a very reduced global longitudinal strain (8.8%) with apical sparing (the worse deformation regions corresponding with basal ones); (D) Hepatic elastography, 78.9kPa in a segment at right hepatic lobe; (E) Cardiac elastography in the basal cardiac septum (2.36kPa); (F) Cardiac elastography in the apical region showing less stiffness comparing to basal regions (0.62kPa). AO: aorta; LA: left atrium; LV: left ventricle; RV: right ventricle. White arrows: regions of interest of the shear wave elastography technique; red arrow: mitral valve thickening; white asterisks: pericardial effusion; red asterisks: increased myocardial thickness." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hereditary transthyretin amyloidosis overview" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "F. Manganelli" 1 => "G.M. Fabrizi" 2 => "M. Luigetti" 3 => "P. Mandich" 4 => "A. Mazzeo" 5 => "D. Pareyson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10072-020-04889-2" "Revista" => array:7 [ "tituloSerie" => "Neurol Sci" "fecha" => "2022" "volumen" => "43" "numero" => "Suppl. 2" "paginaInicial" => "595" "paginaFinal" => "604" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33188616" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evaluation of myocardial stiffness in cardiac amyloidosis using acoustic radiation force impulse and natural shear wave imaging" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F.Q. Jin" 1 => "V. Kakkad" 2 => "D.P. Bradway" 3 => "M. LeFevre" 4 => "J. Kisslo" 5 => "M.G. 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