amyloid cardiomyopathy
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2022 ◽  
Vol 13 ◽  
pp. 215013192110626
Author(s):  
Michel Juarez ◽  
Gaspar Del Rio-Pertuz ◽  
Kanak Parmar ◽  
Melanie C. Bois ◽  
Scott Shurmur ◽  
...  

Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is one of the most common types of cardiac amyloidosis. Amyloid cardiomyopathy more commonly affects men, elderly, and 3% to 4% of the African-American population. ATTR-CM suspicion and diagnosis is challenging; however, awareness of the disease is increasing, and best practices to identify it are being proposed. The approach to suspected cases of ATTR-CM relies on the presence of heart failure, red flag signs and symptoms, and age >65 or >70 for men and women respectively. Little is known about cases when it presents in early ages. Case: We report a 62-year-old African American male with past medical history of hyperlipidemia, prostate cancer, hypertension, bilateral carpal tunnel surgery that had debuted with a cardiac arrhythmia at age 55 and was diagnosed with heart failure several years later. Restrictive cardiomyopathy was suspected, and genetic screening was sent for ATTRm which confirmed a pathogenic trasnthyretin gene mutation. Endomyocardial biopsy was performed which confirmed cardiac amyloid deposition. Discussion: ATTR-CM is a rare disease with an increasing prevalence. Cases with out of proportion signs and symptoms of heart failure with preserved ejection fractions should raise the suspicion of ATTR-CM despite age.


Author(s):  
И.Е. Стрелкова

Амилоидоз – это группа заболеваний, характеризующихся накоплением в интерстиции различных органов и тканей белка специфической фибриллярной структуры. Понятие «амилоидоз» объединяет более 30 различных по своей патофизиологии состояний, в основе каждого из которых лежит нарушение синтеза 30 различных белков-предшественников. Однако 95% амилоидных кардиомиопатий связаны всего с двумя белками: белком, образованным из легких цепей иммуноглобулинов, и белком транстиретином. Определение белка-предшественника является краеугольным камнем ведения пациента с амилоидной кардиомиопатией. Транстиретин – это белок-переносчик тироксина, ретинола и других веществ, выполняющий жизненно важные функции. По наследственным или возрастным причинам происходит нарушение синтеза транстиретина в печени, и образующиеся мономеры, попадая в кровь, образуют токсичные промежуточные продукты и амилоидные фибриллы. Амилоидоз сердца (или амилоидная кардиомиопатия) до недавнего времени считался редким заболеванием. В недалеком прошлом возможности терапии амилоидоза сердца ограничивались назначением диуретиков, антагонистов минералокортикоидных рецепторов и антикоагулянтов, так как другие средства не переносятся пациентами или переносятся в минимальных дозах. С появлением в России первого средства специфического лечения транстиретиновой амилоидной кардиомиопатии резко возросла необходимость в повышении настороженности в отношении транстиретинового амилоидоза среди врачей-терапевтов и кардиологов и во внедрении современных алгоритмов диагностики данного заболевания. Своевременное выявление транстиретинового амилоидоза и грамотная дифференциальная диагностика от других видов амилоидной кардиомиопатии могут сыграть решающую роль в прогнозе заболевания. Препарат тафамидис доказанно снижает частоту госпитализаций и летальность у пациентов с транстиретиновым амилоидозом. Amyloidosis is a group of diseases characterized by accumulation of a protein of a specific fibrillar structure in the interstitium of various organs and tissues. The concept of ≪amyloidosis≫ unites more than 30 different pathophysiological conditions, each of which is based on abnormal synthesis of 30 different precursor proteins. However, 95% of amyloid cardiomyopathies are associated with just two proteins: a protein derived from light chains of immunoglobulins and a protein called transthyretin. Determination of the precursor protein is a cornerstone of management of patients with amyloid cardiomyopathy. Transthyretin is a carrier protein of thyroxine, retinol and other substances, that performs vital functions. For hereditary or age-related reasons, TTR misfolding occurs in the liver. The resulting monomers, entering blood, form toxic intermediate products and amyloid fibrils. Cardiac amyloidosis (or amyloid cardiomyopathy) used to be considered a rare disease. In the recent past, possibilities of therapy for cardiac amyloidosis were limited by prescription of diuretics, mineralocorticoid receptor antagonists and anticoagulants, since other drugs are not tolerated well by patients or are tolerated in minimal doses. Advent of the first drug specific for treatment of transthyretin amyloid cardiomyopathy in Russia increased a need of awareness of ATTR-CM among general practitioners and cardiologists, and introduction of modern diagnostic algorithms for this disease. Timely detection and competent differential diagnosis of ATTR-CM from other types of amyloid cardiomyopathy can play a decisive role in the prognosis of this disease. Tafamidis is a treatment that was shown to reduce mortality and CV-related hospitalization in ATTR-CM patients.


2021 ◽  
Author(s):  
Quentin R. Youmans ◽  
Sanjiv J. Shah ◽  
Sadiya S. Khan

Author(s):  
Perry Elliott ◽  
Brian M. Drachman ◽  
Stephen S. Gottlieb ◽  
James E. Hoffman ◽  
Scott L. Hummel ◽  
...  

Background: Tafamidis is approved in many countries for the treatment of transthyretin amyloid cardiomyopathy. This study reports data on the long-term efficacy of tafamidis from an ongoing long-term extension (LTE) to the pivotal ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial). Methods: Patients with transthyretin amyloid cardiomyopathy who completed ATTR-ACT could enroll in an LTE, continuing with the same tafamidis dose or, if previously treated with placebo, randomized (2:1) to tafamidis meglumine 80 or 20 mg. All patients in the LTE transitioned to tafamidis free acid 61 mg (bioequivalent to tafamidis meglumine 80 mg) following a protocol amendment. In this interim analysis, all-cause mortality was assessed in patients treated with tafamidis meglumine 80 mg in ATTR-ACT continuing in the LTE, compared with those receiving placebo in ATTR-ACT transitioning to tafamidis in the LTE. Results: Median follow-up was 58.5 months in the continuous tafamidis group (n=176) and 57.1 months in the placebo to tafamidis group (n=177). There were 79 (44.9%) deaths with continuous tafamidis and 111 (62.7%) with placebo to tafamidis (hazard ratio, 0.59 [95% CI, 0.44–0.79]; P <0.001). Mortality was also reduced in the continuous tafamidis (versus placebo to tafamidis) subgroups of: variant transthyretin amyloidosis (0.57 [0.33–0.99]; P =0.05) and wild-type transthyretin amyloidosis (0.61 [0.43–0.87]; P =0.006); and baseline New York Heart Association class I and II (0.56 [0.38–0.82]; P =0.003) and class III (0.65 [0.41–1.01]; P =0.06). Conclusions: In the LTE, patients initially treated with tafamidis in ATTR-ACT had substantially better survival than those first treated with placebo, highlighting the importance of early diagnosis and treatment in transthyretin amyloid cardiomyopathy. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01994889 and NCT02791230.


2021 ◽  
Vol 345 ◽  
pp. 4-5
Author(s):  
L.S. Chen ◽  
Y.Y. Oon ◽  
B.K. Chung ◽  
L.K. Thien ◽  
H.B. Chow ◽  
...  

2021 ◽  
Author(s):  
Nobuhiro Tahara ◽  
Olivier Lairez ◽  
Jin Endo ◽  
Atsushi Okada ◽  
Mitsuharu Ueda ◽  
...  

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Courtney M. Campbell ◽  
Cyril Ayuk Mbeng Takem Baiyee ◽  
Salem Almaani ◽  
Naresh Bumma ◽  
Nidhi Sharma ◽  
...  

2021 ◽  
Author(s):  
Mazen Hanna ◽  
Thibaud Damy ◽  
Martha Grogan ◽  
Michelle Stewart ◽  
Balarama Gundapaneni ◽  
...  

This plain language summary describes the results of a study called ATTR-ACT, which was published in the American Journal of Cardiology. In ATTR-ACT, researchers looked at the effects of tafamidis treatment in people with transthyretin amyloid cardiomyopathy (called ATTR-CM for short). Tafamidis is currently available in the USA and other countries as an oral treatment for adults with ATTR-CM. In ATTR-ACT, 441 people with ATTR-CM from 13 different countries took either tafamidis or placebo by mouth for 30 months. First, researchers looked at the effects of tafamidis on the risk of death and hospitalization due to heart problems between the start and the end of the study; they found that these risks were about one-third lower with tafamidis compared with placebo. As described in this summary, researchers also looked at the effects of tafamidis on people’s heart failure symptoms, quality of life, and general health over the 30-month study. People who took part in ATTR-ACT rated these effects using questionnaires filled out before, during, and after the study. More people who took tafamidis saw improvement or no change in their heart failure symptoms and quality of life than people who took placebo. In addition, compared with people taking placebo, people taking tafamidis had less worsening of their general health during the study. These results show the benefits of tafamidis in reducing the declines in quality of life and health that often occur with this debilitating disease. To read the full Plain Language Summary of this article, click on the View Article button above and download the PDF. Clinical Trial Registration: NCT01994889 ( ClinicalTrials.gov )


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3787-3787
Author(s):  
James E Hoffman ◽  
Marla B. Sultan ◽  
Balarama Gundapaneni ◽  
Ronald Witteles

Abstract Introduction: In cardiac amyloidosis (CA), immunoglobulin-derived light chains (AL) and transthyretin (TTR) are the most common amyloidogenic proteins infiltrating the heart. 1 Identification of the specific precursor protein leading to amyloid deposition is needed to establish the correct therapeutic approach. 2 In both AL- and TTR-related CA, an early and accurate diagnosis is critical to achieving the best treatment outcomes. TTR amyloid cardiomyopathy (ATTR-CM) is often misdiagnosed as other causes of heart failure (HF), including AL CA. 3 While almost all patients with AL amyloidosis have elevated serum free light-chain (sFLC) levels and abnormal free kappa:lambda (κ:λ) ratios, 4 patients with ATTR-CM can also have abnormal sFLC levels due to either an unrelated monoclonal gammopathy or relative κ-predominance in renal dysfunction. 2,5 Because ATTR-CM most often occurs in elderly adults and is commonly accompanied by renal comorbidity, we theorized that patients with ATTR-CM may have κ:λ ratios that approach, or exceed, the upper limit of the normal reference range (0.26-1.65 6). High light-chain ratios in these patients have the potential to increase the likelihood of misdiagnosis of a monoclonal plasma cell disorder and may lead to unnecessary referrals to hematologists and/or inappropriate treatments. To explore this theory, we evaluated κ:λ ratios in patients with biopsy-proven ATTR-CM who were enrolled in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT). 7 Methods: In ATTR-ACT, a double-blind, placebo-controlled, randomized study, patients with biopsy-proven ATTR-CM, and without light-chain amyloidosis, received tafamidis or placebo for 30 months. In the current analysis, sFLC levels and κ:λ ratios were assessed in the intent-to-treat population (N=441), excluding patients with a prior diagnosis of monoclonal gammopathies (n=13; defined by MedDRA preferred terms: 'monoclonal gammopathy', 'plasma cell myeloma', 'plasma cell disorder', and 'hypergammaglobulinemia benign monoclonal'). Subgroup analyses were performed by estimated glomerular filtration rate (eGFR) category (≥60 vs ≥40 to &lt;60 vs &lt;40 mL/min/1.73 m 2). Findings were summarized using descriptive statistics (min/max, mean, median, and interquartile range [IQR]). Results: In 422 patients with ATTR-CM and available sFLC data, and without a prior diagnosis of monoclonal gammopathies, the mean κ:λ ratio was 1.45 (median, 1.20 [IQR, 0.98, 1.47]) (Figure). The ratio increased with declining renal function: eGFR ≥60 mL/min/1.73 m 2, mean, 1.25 (median [IQR], 1.11 [0.94, 1.38]); ≥40 to &lt;60 mL/min/1.73 m 2, 1.52 (1.22 [0.99, 1.49]); and &lt;40 mL/min/1.73 m 2, 1.62 (1.30 [1.05, 1.68)]. Conclusions: In patients with biopsy-proven ATTR-CM without known monoclonal gammopathies who were enrolled in ATTR-ACT, the mean κ:λ ratio showed a κ-predominance, often exceeding the upper range of normal in patients with more advanced kidney dysfunction. The findings suggest that individuals with ATTR-CM can have higher sFLC levels than those normally seen in the general population, and such elevations do not necessarily indicate the presence of monoclonal gammopathy of undetermined significance or AL CA. In an era when most patients with ATTR-CM and without monoclonal gammopathies are diagnosed noninvasively using bone scintigraphy, age- and renal-function-based sFLC norms are critical to ensure appropriate use of diagnostic testing modalities. References: 1. Maleszewski JJ. Cardiovasc Pathol. 2015;24:343-50. 2. Donnelly JP, et al. Cleve Clin J Med. 2017;84:12-26. 3. Witteles RM, et al. JACC Heart Fail. 2019;7:709-716. 4. Falk RH, et al. J Am Coll Cardiol. 2016;68:1323-41. 5. Geller HI, et al. Mayo Clin Proc. 2017;92:1800-5. 6. Katzmann JA, et al. Clin Chem. 2002;48:1437-44. 7. Maurer MS, et al. N Engl J Med. 2018;379:1007-16. Figure 1 Figure 1. Disclosures Hoffman: BMS, Celgene: Honoraria. Sultan: Pfizer: Current Employment, Current equity holder in publicly-traded company. Gundapaneni: Pfizer: Current Employment, Current equity holder in publicly-traded company. Witteles: Pfizer: Honoraria, Research Funding; Alnylam: Honoraria, Research Funding; Eidos: Research Funding.


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