In patients with transthyretin amyloid cardiomyopathy (ATTR-CM), the effect of tafamidis on myocardial function using serial speckle tracking echocardiography has not been reported. The purpose of ...this study was to describe the natural history of myocardial function in untreated ATTR-CM and determine the effect of tafamidis on myocardial functional parameters over 12 months of treatment.
A total of 45 subjects with ATTR-CM were retrospectively studied: 23 treated with tafamidis and 22 untreated. Two-dimensional speckle tracking echocardiography was analysed at baseline and 1 year. Serial longitudinal, circumferential, and radial strain, twist, torsion, and myocardial work were measured. Over 1 year, absolute global longitudinal strain (GLS) deteriorated more in the untreated group by a median of 1.1% inter-quartile range (IQR) 0.95 compared with 0.3% (IQR 1) in the tafamidis group (P = 0.02). Myocardial work index and efficiency also deteriorated to a greater degree: 142.5 mmHg% (IQR 197) and 4% (IQR 8), respectively, in the untreated group compared with 61.5 mmHg% (IQR 210) and 1% (IQR 7) in the tafamidis group (P = 0.04). There were no significant between group differences in left ventricular ejection fraction (LVEF), tissue Doppler velocities, circumferential or radial strain, LV twist or torsion at 1 year. The stabilization effect of tafamidis on myocardial function at 1 year did not differ according to baseline GLS, LVEF, or National Amyloidosis Centre disease stage.
In ATTR-CM, tafamidis resulted in a lesser deterioration in GLS, myocardial work index, and efficiency over a 12-month period compared with a cohort not treated with tafamidis.
Amyloidosis as a Systemic Disease in Context Cuddy, Sarah A.M.; Falk, Rodney H.
Canadian journal of cardiology,
March 2020, 2020-Mar, 2020-03-00, 20200301, Volume:
36, Issue:
3
Journal Article
Peer reviewed
The systemic amyloidoses are a group of diseases characterized by the deposition of amyloid, a material formed from misfolding of proteins, in one or more organs. The 2 commonest forms of amyloidosis ...are transthyretin amyloidosis (ATTR), derived from wild-type or mutant transthyretin, and light-chain (AL) amyloidosis, derived from abnormal circulating light chains produced by plasma cell dyscrasia. Both frequently involve the heart, producing an infiltrative cardiomyopathy with restrictive pathophysiology. Although advances in echocardiographic, magnetic resonance, and nuclear imaging have rendered diagnosis of cardiac amyloidosis easier, diagnosis is still often delayed. This review focuses on noncardiac manifestations of AL and TTR amyloidosis that may aid the cardiologist in making an earlier diagnosis of cardiac amyloidosis in a patient with cardiac symptoms (such as periorbital purpura in AL amyloidosis and a history of carpal tunnel syndrome and ruptured biceps tendon in ATTR). It also focuses on the unique challenges that treatment of cardiac amyloidosis poses owing to concomitant noncardiac disease, such as nephrotic syndrome–related edema and hypotension due to autonomic neuropathy, and stresses the importance of a precise typing of amyloidosis and a multidisciplinary approach to therapy.
Les amyloses systémiques forment un groupe de maladies caractérisées par le dépôt de substance amyloïde, constituée de protéines présentant un repliement défectueux, dans un ou plusieurs organes. Les deux formes les plus courantes sont l’amylose à transthyrétine (ATTR), dont le précurseur est une transthyrétine de type sauvage ou mutée, et l’amylose à chaînes légères (AL), dyscrasie plasmocytaire donnant lieu à la surproduction de chaînes légères circulantes. L’une et l’autre touchent fréquemment le cœur et entraînent alors une cardiomyopathie infiltrative à physiopathologie restrictive. Les progrès en échocardiographie, en imagerie par résonance magnétique et en imagerie nucléaire facilitent le diagnostic des amyloses cardiaques. Néanmoins, il n’est pas rare que ces maladies soient diagnostiquées tardivement. Le présent article porte sur les manifestations non cardiaques des amyloses AL et ATTR pouvant aider le cardiologue à poser un diagnostic plus précoce d’amylose cardiaque chez le patient qui présente des symptômes cardiaques (tels que le purpura périorbitaire en cas d’amylose AL et les antécédents de syndrome du canal carpien et de rupture du tendon du biceps en cas d’amylose ATTR). Il aborde aussi les défis uniques que pose le traitement des amyloses cardiaques en présence d’une maladie concomitante non cardiaque, telle que l’œdème du syndrome néphrotique et l’hypotension due à une neuropathie autonome, et souligne l’importance que revêtent le typage précis des amyloses et une démarche thérapeutique multidisciplinaire.
Cardiac magnetic resonance offers multiple facets in the diagnosis, risk stratification, and management of patients with myocardial diseases. Particularly, its feature to precisely monitor disease ...activity lends itself to quantify response to novel therapeutics. This review critically appraises the value of cardiac magnetic resonance imaging biomarkers as surrogate endpoints for prospective clinical trials. The primary focus is to comprehensively outline the value of established cardiac magnetic resonance parameters in myocardial diseases. These include heart failure, cardiac amyloidosis, iron overload cardiomyopathy, hypertrophic cardiomyopathy, cardio-oncology, and inflammatory cardiomyopathies like myocarditis and sarcoidosis.
Background Transthyretin cardiac amyloidosis (ATTR-CMP) is an increasingly recognized and treatable cause of heart failure with preserved ejection fraction. Multimodality cardiac imaging is ...recommended for ATTR-CMP diagnosis, but its cost-effectiveness in current clinical practice has not been well studied. Methods and Results Using a microsimulation model, we compared the cost-effectiveness of a combination of strategies involving
technetium pyrophosphate (PYP), cardiac magnetic resonance imaging, and endomyocardial biopsy for the diagnosis of ATTR-CMP. We developed a decision analytic model to project health care costs and lifetime quality-adjusted life years for symptomatic, older patients who present with congestive heart failure, with an increased left ventricular wall thickness and a 13% prevalence of ATTR-CMP. Rates of clinical events, costs, and quality-of-life values were estimated from published literature. The analysis was conducted from a US health care system perspective with health and cost outcomes discounted annually at 3%. In the base-case scenario, using a fixed tafamidis price of $16 000 annually (previously identified cost-effective price), total health care costs per person were lowest for the PYP-only strategy ($209 415) and highest for endomyocardial biopsy strategy ($215 881). Of the 7 strategies examined, the PYP-only strategy had the highest net monetary benefit using a willingness-to-pay threshold of $100 000/quality-adjusted life year. Results were sensitive to variations in model inputs for PYP and cardiac magnetic resonance imaging specificity, cost of tafamidis, and willingness-to-pay thresholds. Conclusions Our model-based analyses showed that a PYP-only strategy to diagnose ATTR-CMP is the most cost-effective strategy, at willingness-to-pay threshold of $100 000/quality-adjusted life year. At higher threshold ($150 000/quality-adjusted life year), sequential tests involving PYP and cardiac magnetic resonance imaging may be considered cost effective.
PDF
