DONA ORA
Pubblicazioni recenti - cardiac amyloidosis
-
Wild-type ATTR amyloidosis may be associated with unexpected death among the elderly.
Leg Med (Tokyo)2019 Oct;41():101634. doi: S1344-6223(19)30301-3.
Shiozaki Tetsuya, Sato Noriko, Hayashi Tokotaro, Kobayashi Kanya, Asamura Hideki,
Abstract
Wild-type ATTR amyloidosis (ATTR-wt) is characterized by the accumulation of amyloid in the heart, leading to fatal heart failure and arrhythmia. In this study, we investigated the amyloid deposits in the heart from 556 forensic autopsy cases over 60?years of age. The prevalence of ATTR-wt was 5.8% (32 of the 556), with the prevalence increasing as a function of age. We identified an ATTR-wt-specific morbidity rate of 12.3% for patients over 80?years of age, while the prevalence among individuals over 90?years of age was 34.9%. In none of these 32 cases had a clinical diagnosis of ATTR-wt been made. In 29 of the 32 cases found to be ATTR-wt positive, an obvious extraneous cause of death was identified and included burning, drowning, hypothermia, suicide, and traffic accident. On the other hand, heart failure due to ATTR-wt was confirmed as the cause of death in 3 of the 32 cases. It is suggested that ATTR-wt may be associated with unexpected death among the elderly.
Copyright © 2019 Elsevier B.V. All rights reserved.
Guarda su PubMed
-
Cardiac involvement in heavy and light chain amyloidosis: A case report and literature review.
Medicine (Baltimore)2019 Nov;98(46):e17999. doi: 10.1097/MD.0000000000017999.
Otaka Yukihiro, Nakazato Yoichi, Tsutsui Takaaki, Tamura Jun'ichi,
Abstract
INTRODUCTION:
Heavy and light chain amyloidosis is an extremely rare condition. There are few reports referring to the clinical impact of cardiac involvement in heavy and light chain amyloidosis, and the significance of myocardial impairment has not yet been completely explained.
PATIENT CONCERNS:
A 66-year-old Japanese man was admitted to our hospital presenting with nephrotic syndrome and congestive heart failure.
DIAGNOSIS:
Kidney and endoscopic gastric mucosal biopsy demonstrated congophilic hyalinization in most of the glomeruli and surrounding vessel walls, which were highly positive for immunoglobulin A and lambda. Finally, the patient was diagnosed as an atypical multiple myeloma with systemic heavy and light chain amyloidosis.
INTERVENTIONS:
The patient was referred to hematology for further treatment and was moved to another hospital for the administration of chemotherapy using melphalan and dexamethasone.
OUTCOMES:
The patient was still alive after 15-month follow-up from the initial diagnosis.
CONCLUSION:
Initial screening and follow-up for cardiac involvement are important for heavy and light chain amyloidosis. Further investigation for the prognosis of heavy and light chain amyloidosis is required to improve the strategies of diagnosis and treatment options for patients with this disease.
Guarda su PubMed
-
Transthyretin Cardiac Amyloidosis as Diagnosed by 99mTc-PYP Scanning in Patients with Acute Heart Failure and Preserved Ejection Fraction.
Crit Pathw Cardiol2019 Dec;18(4):195-199. doi: 10.1097/HPC.0000000000000183.
Lo Presti Saberio, Horvath Sofia A, Mihos Christos G, Rajadhyaksha Chetan, McCloskey Veronica, Santana Orlando,
Abstract
Transthyretin amyloid deposition is present in 17% of autopsies of patients with heart failure and a preserved ejection fraction (HFpEF). Technetium-pyrophosphate scintigraphy (Tc-PYP) is sensitive and specific to diagnose cardiac transthyretin amyloid deposition (ATTR). The prevalence of ATTR by Tc-PYP was evaluated along with echocardiographic parameters in patients with HFpEF. One-hundred consecutive patients with HFpEF, who had Tc-PYP, were retrospectively evaluated. Echocardiographic variables were analyzed to compare patients with positive versus negative ATTR infiltration. Myocardial ATTR was present in 19% of patients. Individuals with ATTR were older with a mean age of 82?±?7 versus 75?±?13 years (P = 0.03), had increased left ventricular hypertrophy with the interventricular septum measuring 1.6 (IQR, 1.4-2.0) versus 1.4 (IQR, 1.3-1.6) cm (P = 0.002), had a greater mean left ventricular mass index of 160?±?50?g/m versus 131?±?44?g/m (P = 0.01), and a reduced global longitudinal strain measuring -11% (IQR, -9 to -12) versus -12% (IQR, -10 to -16), P = 0.04. The prevalence of ATTR myocardial deposition demonstrated by Tc-PYP in patients with HFpEF is comparable to that of autopsy studies. It is more common in older patients, with increased left ventricular hypertrophy and reduced global longitudinal strain.
Guarda su PubMed
-
Amyloidosis in surgically resected atrial appendages: a study of 345 consecutive cases with clinical implications.
Mod Pathol2019 Nov;():. doi: 10.1038/s41379-019-0407-5.
Fayyaz Ahmed U, Bois Melanie C, Dasari Surendra, Padmanabhan Deepak, Vrana Julie A, Stulak John M, Edwards William D, Kurtin Paul J, Asirvatham Samuel J, Grogan Martha, Maleszewski Joseph J,
Abstract
Histomorphologic parameters of atrial appendages removed during the Cox-Maze procedure have been shown to correlate with recurrence of atrial fibrillation. While amyloid deposition has been noted within atrial appendages, the incidence and significance remains incompletely understood. More accurate amyloid typing methodologies and targeted pharmacotherapeutics have recently been developed, prompting pathologists to provide more detailed information about the type of amyloid identified in such samples. This study sought to fully characterize the morphologic characteristics of atrial amyloid as well as its incidence and clinical significance. Tissue archives were queried for atrial appendages removed during the cardiac surgeries (2010-2014). Patient demographics, imaging features, and salient clinical findings were recorded. Pattern and extent of amyloid deposition were recorded. Typing of the amyloid protein, when present, was performed on a subset of cases by laser capture microdissection with mass spectrometry-based proteomic analysis. A total of 383 atrial appendages from 345 consecutive patients were included in the study (mean age, 69 years; range, 26-92 years). Amyloid was present in 46% of patients. A linear relationship was observed between age and presence of atrial amyloidosis. Women were more likely to have atrial amyloidosis. Two distinct morphologies of amyloid were observed: filamentous and nonfilamentous, and correlated perfectly with amyloid type (filamentous?=?AANF-type amyloid; nonfilamentous?=?ATTR-type amyloid). Filamentous deposits were observed in 91% of those with amyloid. Amyloid was more likely to be found in the left atrial appendage than the right. Patients with atrial amyloid, irrespective of type, were more likely to have experienced stroke or TIA and more likely to have atrial arrhythmia preoperatively. Postoperatively, those with atrial amyloid are more likely to experience recurrence of arrhythmia than those who did not have atrial amyloid. Understanding the morphologic characteristics of AANF-type amyloid will allow for identification by the light microscopy and obviates the need for expensive ancillary typing techniques. The finding of nonfilamentous amyloid, should still prompt confirmation of amyloid type so that targeted therapy may be employed.
Guarda su PubMed
-
Atrial Fibrillation in the Elderly: The Role of Sub-Clinical Isolated Cardiac Amyloidosis.
Sci Rep2019 Nov;9(1):16584. doi: 10.1038/s41598-019-53119-z.
Krishnappa Darshan, Dykoski Richard, Can Ilknur, Mbai Mackenzie, Anand Inder S, Florea Viorel, Chandrashekar Y S, Li Jian-Ming, Tholakanahalli Venkatakrishna N,
Abstract
Amyloid infiltration of the atrium is described in patients with valvular heart disease and is associated with an increased risk for atrial fibrillation(AF) while amyloid deposits in the ventricles is increasingly being diagnosed in patients with HFpEF. The role of amyloid deposits in patients with AF without valvular heart disease, which represents the most common form of AF globally, is undefined. In this study, we sought to assess the prevalence of sub-clinical isolated cardiac amyloidosis (ICA) at autopsy and the odds of AF in these patients. A total of 1083 patients were included in the study and 3.1% of patients were found to have asymptomatic ICA. Patients with ICA were older and had a higher odds of AF independent of age and CHADSVASc score. Amongst patients with AF, those with ICA were more likely to have persistent forms of AF and had a lower sinus rhythm P-wave amplitude. Further studies are required to further define this entity, identify imaging modalities to aid in antemortem diagnosis of ICA and to establish the optimal management strategies in these patients.
Guarda su PubMed
-
Clinical characteristics and prognosis of Chinese patients with hereditary transthyretin amyloid cardiomyopathy.
Orphanet J Rare Dis2019 Nov;14(1):251. doi: 10.1186/s13023-019-1235-x.
He Shan, Tian Zhuang, Guan Hongzhi, Li Jian, Fang Quan, Zhang Shuyang,
Abstract
BACKGROUND:
Hereditary transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly recognized progressive cardiomyopathy with heterogenous clinical manifestations that lead to its misdiagnosis and poor prognosis. This study was performed to describe the clinical characteristics and natural history of Chinese patients to improve clinical awareness of this condition.
METHODS:
In this study, we retrospectively investigated 23 patients with a confirmed diagnosis of hereditary ATTR-CM in Peking Union Medical College hospital from From January 1, 2000 to December 31, 2018.
RESULTS:
In all, 16 patients (69.6%) were males, the median age at disease onset was 45 (33,55) years old. The median duration from symptom onset to diagnosis was 30 (18,46) months. Phenotypes were classified as exclusively cardiac (n?=?1, 4.3%) and mixed type (n?=?22, 95.6%). The common mutations were Gly47Arg (7 patients [30.4%]) and Val30Ala (3 patients [13%]). Ventricular hypertrophy was observed in 23 (100%) patients, the mean thickness of the ventricular septum was 16.1?±?3.9?mm, the mean thickness of the left ventricular posterior wall was 15.1?±?2.8?mm. The mean left ventricle ejection fraction (LVEF) was 57.3?±?11.9% and only 5 patients (21.7%) had LVEF
CONCLUSIONS:
The clinical characteristics of ATTR are heterogeneous: men are more likely to be affected and onset symptoms are not obvious in the heart and mainly include peripheral neuropathy and autonomic neuropathy; however, LV hypertrophy, especially a thick ventricular septum and posterior wall with preserved LVEF, are often detected on echocardiography. Abnormal ECG manifestations are common. The prognosis is poor, and patients with EF >?50% have better survival. Clinicians should be more aware of the complex clinical profile of ATTR amyloidosis to avoid misdiagnosis in practice.
Guarda su PubMed
-
Inotersen therapy of transthyretin amyloid cardiomyopathy.
Amyloid2019 Nov;():1-7. doi: 10.1080/13506129.2019.1685487.
Dasgupta Noel R, Rissing Stacy M, Smith Jessica, Jung Jeesun, Benson Merrill D,
Abstract
Cardiomyopathy is a major cause of death in patients with systemic transthyretin amyloidosis. Long term effect of therapy designed to inhibit hepatic production of the amyloid precursor has not been established in cardiomyopathy. The purpose of this study was to evaluate the long term safety and efficacy of transthyretin specific antisense oligonucleotide therapy, inotersen, in transthyretin cardiomyopathy. Patients with hereditary or wildtype transthyretin cardiomyopathy (NYHA I-III) with an LV wall thickness [Formula: see text]1.3?cm and clinical evidence of congestive heart failure were eligible for this single centre, open label protocol. Safety and cardiac structural and functional parameters were prospectively studied. As of October 2018, 33 subjects have entered the study. Twenty have completed 1?year, 16 have completed 2?years, and 14 have completed three years. At the 2?year time point, mean LV mass decreased by 8.4% as measured by MRI, and exercise tolerance increased by 20.2 metres as measured by 6?minute walk test. Further positive indicators were noted at 3?years, with LV mass decreasing by 11.4% and 6MWT increasing by 16.2 metres. Long term treatment of amyloid cardiomyopathy with inotersen is safe and effective in inhibiting progression and potentially reversing amyloid burden.
Guarda su PubMed
-
Native aortic valve endocarditis with Morganella morganii in a patient with multiple myeloma and valvular amyloidosis: a case report.
BMC Infect Dis2019 Nov;19(1):957. doi: 10.1186/s12879-019-4511-4.
van Bentum Renée, Nieken Judith, de Waal Esther, Hoogendoorn Mels,
Abstract
BACKGROUND:
Patients with multiple myeloma (MM) are known to be immune incompetent and experience higher incidences of infectious diseases. However, infective endocarditis (IE) is rarely observed in patients with MM and Morganella morganii (M. morganii) has rarely been associated with IE.
CASE PRESENTATION:
A 72-year-old female receiving 4th line treatment for MM presented with fever and concomitant confusion. Urinary culture revealed growth of Escherichia coli, wherefore broadspectrum penicillin and high-dose corticosteroids were initiated. However, blood cultures showed growth of M. morganii. Fluoroquinolone was added due to penicillin-resistance of the Morganella species. Two days after admission, the patient acutely deteriorated with hemodynamic instability. Gentamicin and high dose corticosteroids were added. Echocardiography showed marked aortic valve vegetation with severe aortic valve regurgitation, leading to the diagnosis of bacterial endocarditis of the native aortic valve. Shortly after diagnosis, the patient died. At autopsy, vegetation with gram-negative rods in the native aortic valve was observed, confirming the diagnosis of M. morganii-endocarditis. Additional staining for amyloid confirmed advanced light-chain (AL) amyloidosis with extensive amyloid depositions of the aortic valve and valvular damage as complications of her MM.
CONCLUSIONS:
Our case suggests that IE with M. morganii was facilitated by the combination of the cardiac amyloidosis with valvular impairment and the profound immune deficiency caused by the several chemo-immunomodulatory treatment lines and the MM itself. This case further illustrates that awareness for rare opportunistic infections in an era with growing potential of combined chemoimmunotherapy is warranted.
Guarda su PubMed
-
Leading RNA Interference Therapeutics Part 1: Silencing Hereditary Transthyretin Amyloidosis, with a Focus on Patisiran.
Mol Diagn Ther2019 Nov;():. doi: 10.1007/s40291-019-00434-w.
Titze-de-Almeida Simoneide S, Brandão Pedro Renato de Paula, Faber Ingrid, Titze-de-Almeida Ricardo,
Abstract
In 2018, patisiran was the first-ever RNA interference (RNAi)-based drug approved by the US Food and Drug Administration. Now pharmacology textbooks may include a new drug class that results in the effect first described by Fire and Mello 2 decades ago: post-transcriptional gene silencing by a small-interfering RNA (siRNA). Patients with hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) present with mutations in the transthyretin (TTR) gene that lead to the formation of amyloid deposits in peripheral nerves and heart. The disease may also affect the eye and central nervous system. The formulation of patisiran comprises the RNAi drug encapsulated into a nanoparticle especially developed to deliver the anti-TTR siRNA into the main TTR producer: the liver. Hepatic cells contain apolipoprotein E receptors that recognize ApoE proteins opsonized in the lipid carrier and internalize the drug by endocytosis. Lipid vesicles are disrupted in the cell cytoplasm, and siRNAs are free to trigger the RNAi-based TTR gene silencing. The silencing process involves the binding of siRNA guide strand to 3'-untranslated region sequence of both mutant and wild-type TTR messenger RNA, which culminates in the TTR mRNA cleavage by the RNA-induced silencing complex (RISC) as the first biochemical drug effect. Patisiran 0.3 mg/kg is administered intravenously every 3 weeks. Patients require premedication with anti-inflammatory drugs and antagonists of histamine H and H receptors to prevent infusion-related reactions and may require vitamin A supplementation. Following patisiran treatment, TTR knockdown remained stable for at least 2 years. Adverse effects were mild to moderate with unchanged hematological, renal, or hepatic parameters. No drug-related severe adverse effects occurred in a 24-month follow-up phase II open-label extension study. At the recommended dosage of patisiran, C and AUC values (mean ± standard deviation) were 7.15 ± 2.14 ?g/mL and 184 ± 159 ?g·h/mL, respectively. The drug showed stability in circulation with?>?95% encapsulated in lipid particles. Metabolization occurred by ribonuclease enzymes, with less than 1% excreted unchanged in the urine. Patisiran ameliorated neuropathy impairment according to the modified Neuropathy Impairment Score + 7 analysis of the phase III study. The Norfolk Quality of Life-Diabetic Neuropathy score and gait speed improved in 51% of the patisiran-treated group in 18 months. Additionally, the modified body mass index showed positive outcomes. Altogether, the data across phase I-III clinical trials points to patisiran as an effective and safe drug for the treatment of hATTR amyloidosis. It is hoped that real-world data from a larger number of patients treated with patisiran will confirm the effectiveness of this first-approved siRNA-based drug.
Guarda su PubMed
-
The current status of quantitative SPECT/CT in the assessment of transthyretin cardiac amyloidosis.
J Nucl Cardiol2019 Nov;():. doi: 10.1007/s12350-019-01935-1.
Ramsay Stuart C, Cuscaden Claire,
Abstract
Nuclear medicine bone scans differentiate ATTR cardiomyopathy (ATTR-CM) from light chain cardiac amyloidosis and other myocardial disorders, helping to make the diagnosis without biopsy. Standard bone scans are not absolutely quantitative, so are assessed by comparing the heart to other tissues. The standard visual scoring system compares heart to bone. This accurately diagnoses ATTR-CM and has been validated in a multicenter study, but has limitations. Semiquantitative techniques including heart/contralateral thorax (H/CL) and heart/whole body ratio (H/WB) improve on visual scoring but still rely on extracardiac sites as comparators. Absolute quantitation of myocardial uptake using quantitative SPECT should help overcome these shortcomings. In ATTR-CM, this technique is practical, accurately makes the diagnosis and provides information that is not identical to visual scores. However, more work needs to be done. The reproducibility in ATTR-CM must be tested. Larger studies need to be undertaken to determine whether quantitative SPECT measurements can assess prognosis, disease progression or treatment response. As ATTR-CM is relatively uncommon multicenter trials will help recruit enough subjects to answer these questions. Accurate measurement techniques are needed in ATTR-CM to enable appropriate use of proven therapy and to conduct trials of new therapeutic agents. Quantitative bone scans offer a promising avenue.
Guarda su PubMed
-
Facial Paralysis as Initial Manifestation of Light-chain Amyloidosis.
Cureus2019 Aug;11(8):e5521. doi: 10.7759/cureus.5521.
Martins André M, Ferreira Filipa S, Leite Ines M, Fonseca Marina, Victorino Rui,
Abstract
Light-chain (AL) amyloidosis is a systemic disease capable of damaging virtually all body tissues. Neurologic involvement is commonly manifested by dysautonomia and peripheral nervous system affection. However, from 1970 to 2018, only 12 cases of cranial nerve injury associated with AL amyloidosis were identified. Eight months before hospital admission, a previously healthy 61-year-old man complained to his general practitioner of episodes of lipotimia while walking and, three months later, he developed a left facial nerve paralysis assumed, at that time, to be idiopathic. After two months, he started complaining of dyspnea and lower limb edema. Physical examination at admission revealed hypotension, exuberant peripheral edema, jugular venous distention, periorbital purpura and left peripheral facial paralysis. He had elevated troponin and brain natriuretic peptide, mild proteinuria and a monoclonal gammopathy IgG/lambda. Bone marrow biopsy revealed 20% plasmocytes and cardiac ultrasound showed diffuse hypokinesia and restrictive filling pattern. AL amyloidosis with major cardiac involvement was considered and a rectal biopsy revealed amyloid protein. Chemotherapy protocol to AL amyloidosis was initiated but cardiac disease progressed leading to death. Persistent facial nerve paralysis should be considered as a rare initial manifestation of AL amyloidosis allowing an earlier diagnosis.
Copyright © 2019, Martins et al.
Guarda su PubMed
-
Amyloidosis: diagnosis and new therapies for a misunderstood and misdiagnosed disease.
Neurodegener Dis Manag2019 Nov;():. doi: 10.2217/nmt-2019-0020.
Thomas Victoria E, Smith Justin, Benson Merrill D, Dasgupta Noel R,
Abstract
Amyloidosis is a group of diseases characterized by extracellular deposition of amyloid fibril complexes. Fibril deposition results in organ dysfunction and possible failure. Amyloidosis is regarded as a rare disease, but in general is underdiagnosed. The two main types of systemic amyloidosis are immunoglobulin light chain and transthyretin amyloidosis. The increased availability of noninvasive cardiac imaging, genetic testing and improved laboratory assays and protein identification methods have led to increased diagnosis. However, in many cases, the diagnosis is not made until the patient develops organ impairment. Earlier diagnosis is required to prevent irreversible organ failure. Novel treatments for immunoglobulin light chain and transthyretin amyloidosis that halt disease progression, prolong and increase quality of life have recently become available.
Guarda su PubMed
-
Comparison of tissue tracking assessment by cardiovascular magnetic resonance for cardiac amyloidosis and hypertrophic cardiomyopathy.
Acta Radiol2019 Nov;():284185119883714. doi: 10.1177/0284185119883714.
Jung Hye Na, Kim Sung Mok, Lee Jeong Hyun, Kim Yiseul, Lee Sang-Chol, Jeon Eun-Seok, Yong Hwan Seok, Choe Yeon Hyeon,
Guarda su PubMed
-
2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy: Executive summary.
Heart Rhythm2019 Nov;16(11):e373-e407. doi: S1547-5271(19)30852-5.
Towbin Jeffrey A, McKenna William J, Abrams Dominic J, Ackerman Michael J, Calkins Hugh, Darrieux Francisco C C, Daubert James P, de Chillou Christian, DePasquale Eugene C, Desai Milind Y, Estes N A Mark, Hua Wei, Indik Julia H, Ingles Jodie, James Cynthia A, John Roy M, Judge Daniel P, Keegan Roberto, Krahn Andrew D, Link Mark S, Marcus Frank I, McLeod Christopher J, Mestroni Luisa, Priori Silvia G, Saffitz Jeffrey E, Sanatani Shubhayan, Shimizu Wataru, van Tintelen J Peter, Wilde Arthur A M, Zareba Wojciech,
Abstract
Arrhythmogenic cardiomyopathy (ACM) is an arrhythmogenic disorder of the myocardium not secondary to ischemic, hypertensive, or valvular heart disease. ACM incorporates a broad spectrum of genetic, systemic, infectious, and inflammatory disorders. This designation includes, but is not limited to, arrhythmogenic right/left ventricular cardiomyopathy, cardiac amyloidosis, sarcoidosis, Chagas disease, and left ventricular noncompaction. The ACM phenotype overlaps with other cardiomyopathies, particularly dilated cardiomyopathy with arrhythmia presentation that may be associated with ventricular dilatation and/or impaired systolic function. This expert consensus statement provides the clinician with guidance on evaluation and management of ACM and includes clinically relevant information on genetics and disease mechanisms. PICO questions were utilized to evaluate contemporary evidence and provide clinical guidance related to exercise in arrhythmogenic right ventricular cardiomyopathy. Recommendations were developed and approved by an expert writing group, after a systematic literature search with evidence tables, and discussion of their own clinical experience, to present the current knowledge in the field. Each recommendation is presented using the Class of Recommendation and Level of Evidence system formulated by the American College of Cardiology and the American Heart Association and is accompanied by references and explanatory text to provide essential context. The ongoing recognition of the genetic basis of ACM provides the opportunity to examine the diverse triggers and potential common pathway for the development of disease and arrhythmia.
Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
Guarda su PubMed
-
Sporadic Cardiac Amyloidosis by Amyloidogenic Transthyretin V122I Variant.
Int Heart J2019 Oct;():. doi: 10.1536/ihj.19-134.
Nehashi Takeshi, Oikawa Masayoshi, Amami Kazuaki, Kanno Yuki, Yokokawa Tetsuro, Misaka Tomofumi, Yamada Shinya, Kunii Hiroyuki, Nakazato Kazuhiko, Ishida Takafumi, Takeishi Yasuchika,
Abstract
Hereditary ATTR amyloid cardiomyopathy is defined as the intramyocardial deposition of amyloid fibrils derived from the mutation of transthyretin (TTR). A 51-year-old man was referred to our hospital for congestive heart failure. He and his family had no past history of heart diseases. Echocardiography showed remarkable left ventricular hypertrophy and reduced ejection fraction. Endomyocardial biopsy specimens presented positive staining of Congo-Red and transthyretin. A genetic test showed heterozygous V122I TTR gene mutation, which is very rare in Japan. We diagnosed him as with sporadic ATTR amyloidosis with mutation, and tafamidis was administered to stabilize TTR tetramer. Since the phenotype of ATTR amyloidosis varies depending on its penetration rate, it is crucial to always keep in mind the possibility of hereditary ATTR amyloidosis even in the case of amyloidosis with no clear family history.
Guarda su PubMed
-
The diagnostic challenge of cardiomyopathies: When should we suspect cardiac amyloidosis?
J Nucl Cardiol2019 Oct;():. doi: 10.1007/s12350-019-01922-6.
Gobbo Magali, Bender Daniel, Mosto Hugo, Sueiro Héctor, Mocskos Andrea, Tepper Rita, Carbajales Justo,
Guarda su PubMed
-
Phenome-wide association study of TTR and RBP4 genes in 361,194 individuals reveals novel insights in the genetics of hereditary and wildtype transthyretin amyloidoses.
Hum Genet2019 Oct;():. doi: 10.1007/s00439-019-02078-6.
De Lillo Antonella, De Angelis Flavio, Di Girolamo Marco, Luigetti Marco, Frusconi Sabrina, Manfellotto Dario, Fuciarelli Maria, Polimanti Renato,
Abstract
Transthyretin (TTR) gene has a causal role in a hereditary form of amyloidosis (ATTRm) and is potentially involved in the risk of wild-type transthyretin amyloidosis (ATTRwt). To understand the genetics of ATTRm and ATTRwt, we conducted a phenome-wide association study of TTR gene in 361,194 participants of European descent testing coding and non-coding variants. Among the 382 clinically relevant phenotypes tested, TTR non-coding variants were associated with 26 phenotypic traits after multiple testing correction. These included signs related to both ATTRm and ATTRwt such as chronic ischaemic heart disease (rs140226130, p?=?2.00?×?10), heart failure (rs73956431, p?=?2.74?×?10), atrial fibrillation (rs10163755, p?=?4.63?×?10), dysphagia (rs2949506, p?=?3.95?×?10), intestine diseases (rs970866, p?=?7.14?×?10) and anxiety (rs554521234, p?=?8.85?×?10). Consistent results were observed for TTR disease-causing mutation Val122Ile (rs76992529) with respect to carpal tunnel syndrome (p?=?6.41?×?10) and mononeuropathies of upper limbs (p?=?1.22?×?10). Sex differences were also observed in line with ATTRm and ATTRwt epidemiology. Additionally, we explored possible modifier genes related to TTR function, observing convergent associations of RBP4 variants with the clinical phenotypes associated with TTR locus. In conclusion, we provide novel insights regarding the molecular basis of ATTRm and ATTRwt based on large-scale cohort, expanding our understanding of the phenotypic spectrum associated with TTR gene variation.
Guarda su PubMed
-
A workflow for patient-specific fluid-structure interaction analysis of the mitral valve: A proof of concept on a mitral regurgitation case.
Med Eng Phys2019 Oct;():. doi: S1350-4533(19)30197-3.
Biffi Benedetta, Gritti Maurizio, Grasso Agata, Milano Elena G, Fontana Marianna, Alkareef Hamad, Davar Joseph, Jeetley Paramijit, Whelan Carol, Anderson Sarah, Lorusso Donatella, Sauvage Emilie, Maria Bosi Giorgia, Schievano Silvia, Capelli Claudio,
Abstract
The mechanics of the mitral valve (MV) are the result of the interaction of different anatomical structures complexly arranged within the left heart (LH), with the blood flow. MV structure abnormalities might cause valve regurgitation which in turn can lead to heart failure. Patient-specific computational models of the MV could provide a personalised understanding of MV mechanics, dysfunctions and possible interventions. In this study, we propose a semi-automatic pipeline for MV modelling based on the integration of state-of-the-art medical imaging, i.e. cardiac magnetic resonance (CMR) and 3D transoesophageal-echocardiogram (TOE) with fluid-structure interaction (FSI) simulations. An FSI model of a patient with MV regurgitation was implemented using the finite element (FE) method and smoothed particle hydrodynamics (SPH). Our study showed the feasibility of combining image information and computer simulations to reproduce patient-specific MV mechanics as seen on medical images, and the potential for efficient in-silico studies of MV disease, personalised treatments and device design.
Copyright © 2019. Published by Elsevier Ltd.
Guarda su PubMed
-
Red flags in cardiac amyloidosis.
Eur J Prev Cardiol2019 Oct;():2047487319884371. doi: 10.1177/2047487319884371.
Kwok Chun Shing, Farzaneh-Far Afshin, Mamas Mamas A,
Guarda su PubMed
-
Primary treatment of light-chain amyloidosis with bortezomib, lenalidomide, and dexamethasone.
Blood Adv2019 Oct;3(20):3002-3009. doi: 10.1182/bloodadvances.2019000147.
Kastritis Efstathios, Dialoupi Ioanna, Gavriatopoulou Maria, Roussou Maria, Kanellias Nikolaos, Fotiou Despina, Ntanasis-Stathopoulos Ioannis, Papadopoulou Elektra, Ziogas Dimitrios C, Stamatelopoulos Kimon, Manios Efstathios, Ntalianis Argyrios, Eleutherakis-Papaiakovou Evangelos, Papanikolaou Asimina, Migkou Magdalini, Papanota Aristea-Maria, Gakiopoulou Harikleia, Psimenou Erasmia, Tselegkidi Maria Irini, Tsitsilonis Ourania, Kostopoulos Ioannis, Terpos Evangelos, Dimopoulos Meletios A,
Abstract
Bortezomib and dexamethasone with cyclophosphamide (CyBorD) or melphalan (BMDex) are commonly used primary treatments for light-chain (AL) amyloidosis, but limited data exist on bortezomib with immunomodulatory drug combinations. We report our experience with primary therapy with a bortezomib, lenalidomide, and dexamethasone (VRD) "light" regimen in 34 consecutive patients with AL amyloidosis. The majority (79%) had cardiac involvement, 15% and 23% were Mayo stage 3A and 3B, respectively, and 54% had renal involvement. After the first VRD cycle, 71% of patients achieved a hematologic response (44% at least very good partial response [VGPR]). On intent to treat, 11 (32%) achieved a complete response (of whom 5 of 11 were minimal residual disease [MRD] negative at 10-5), 17 (50%) a VGPR, and 2 (7%) a partial response. The 12-month survival was 73%. Starting lenalidomide dose was 5 mg in 86% of patients. Hematologic toxicity was mild; nonhematologic toxicities included rash (grade 3/4 [16%]), infections (grade ?3 [12%]), constipation (grade ?3 [9%]), and peripheral neuropathy (grade 2 [20%]); 37.5% of patients required lenalidomide dose reduction, 27% discontinued lenalidomide, 38% required bortezomib dose reduction, and 12% discontinued bortezomib. We compared VRD to CyBorD in 68 patients matched for Mayo stage and baseline difference between involved minus uninvolved serum free light chain levels, and observed a trend for deeper response at 3 and 6 months with VRD. In conclusion, VRD can be an active regimen for newly diagnosed patients with AL amyloidosis able to induce very deep hematologic responses at the expense of increased toxicity.
© 2019 by The American Society of Hematology.
Guarda su PubMed
