Recognition and Implications of Undiagnosed Cardiac Amyloid Patients in HFpEF Trials

2021 ◽  
Author(s):  
Richard K. Cheng ◽  
Mathew S. Maurer
Keyword(s):  
Cardiac Amyloid

A key role for comprehensive geriatric assessment in aortic valve replacement

2020 ◽  
Vol 13 (12) ◽  
pp. e237031
Author(s):  
Karim Hussien El-Shakankery ◽  
Luis Mieiro
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Replacement ◽  
Valve Replacement ◽  
Geriatric Assessment ◽  
Comprehensive Geriatric Assessment ◽  
Small Vessel Disease ◽  
Postoperative Recovery ◽  
Medical Patients ◽  
Surgical Aortic Valve Replacement ◽  
Cardiac Amyloid

As our population ages, the demand for surgical services in older people is increasing exponentially. Shown to be indispensable in the care of medical patients, use of the comprehensive geriatric assessment (CGA) is also growing in the perioperative setting. We present the case of a previously independent 82-year-old man who underwent a standard preoperative assessment and surgical aortic valve replacement. In the 7 months that followed, prior to his death, he suffered a rapid functional decline contributed to by slow postoperative recovery, delirium and recurrent falls. Post-mortem revealed cardiac amyloid deposition and extensive small vessel disease in the brain. This case highlights the importance of the CGA in the perioperative management of older patients, especially in identification and optimisation of geriatric syndromes and consideration of less-invasive alternative treatments. We review the existing literature on CGA use in cardiothoracic and vascular surgical settings, drawing on experiences learnt from the above case.

scholarly journals A human antibody selective for transthyretin amyloid removes cardiac amyloid through phagocytic immune cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Aubin Michalon ◽  
Andreas Hagenbuch ◽  
Christian Huy ◽  
Evita Varela ◽  
Benoit Combaluzier ◽  
...  
Keyword(s):  
Immune Cells ◽  
Ex Vivo ◽  
Phase 1 ◽  
Hereditary Disease ◽  
Elderly Subjects ◽  
Human Antibody ◽  
Cardiac Amyloid ◽  
Healthy Elderly ◽  
Ongoing Phase

AbstractTransthyretin amyloid (ATTR) cardiomyopathy is a debilitating disease leading to heart failure and death. It is characterized by the deposition of extracellular ATTR fibrils in the myocardium. Reducing myocardial ATTR load is a therapeutic goal anticipated to translate into restored cardiac function and improved patient survival. For this purpose, we developed the selective anti-ATTR antibody NI301A, a recombinant human monoclonal immunoglobulin G1. NI301A was cloned following comprehensive analyses of memory B cell repertoires derived from healthy elderly subjects. NI301A binds selectively with high affinity to the disease-associated ATTR aggregates of either wild-type or variant ATTR related to sporadic or hereditary disease, respectively. It does not bind physiological transthyretin. NI301A removes ATTR deposits ex vivo from patient-derived myocardium by macrophages, as well as in vivo from mice grafted with patient-derived ATTR fibrils in a dose- and time-dependent fashion. The biological activity of ATTR removal involves antibody-mediated activation of phagocytic immune cells including macrophages. These data support the evaluation of safety and tolerability of NI301A in an ongoing phase 1 clinical trial in patients with ATTR cardiomyopathy.

Regression of cardiac amyloid deposits with novel therapeutics: reaching new frontiers in cardiac ATTR amyloidosis

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L Chacko ◽  
A Martinez-Naharro ◽  
T Kotecha ◽  
R Martone ◽  
D Hutt ◽  
...  
Keyword(s):  
Treatment Group ◽  
Cardiac Amyloidosis ◽  
T1 Mapping ◽  
Group Versus ◽  
Control Group ◽  
Cardiac Amyloid ◽  
Attr Amyloidosis ◽  
Amyloid Load ◽  
The Impact

Abstract Background Cardiac involvement is the main driver of outcome in ATTR amyloidosis. Advances in therapeutics hold potential in transforming the course of the disease but the impact on cardiac amyloid load is unknown. The aim of this study was to evaluate the impact of patisiran, a new double stranded RNA based gene silencing therapy and a stabilizer, diflunisal, on cardiac amyloid load as measured by CMR and T1 mapping, in patients with ATTR amyloidosis. Methods and results Thirty-two patients with hereditary cardiac amyloidosis were studied. Sixteen patients received treatment with patisiran, and sixteen control subjects did not receive any disease modifying treatment. Patients were assessed with echocardiogram, CMR, NT-proBNP and six-minute walk time measurements at baseline and at 1 year (Mean interval 11.45±3.08 months in treatment group, mean interval 12.82±5.06 months in the control group). CMR analysis comprised LV volumes, T1 mapping to measure the extracellular volume (ECV) occupied by amyloid, T2 mapping and late gadolinium enhancement imaging. At 1-year follow-up, there was a substantial reduction in cardiac amyloid burden, in keeping with cardiac amyloid regression in 45% of patients on treatment. Overall the treatment group showed a reduction in ECV at 1 year follow up compared to an increase in ECV at 1 year in the control group (−1.37%, 95% CI: −3.43 to 0.68% versus 5.02%, 95% CI: 2.86% to 7.18% respectively, p<0.001). The treatment group also showed an improvement in change in 6MWT at 1 year follow up compared to 6MWT at 1 year in the control group (−8.12 meters, 95% CI: −50.8 to 34.6 meters in the treatment group versus −132.27 meters, 95% CI: −216 to −48.6 meters in the control group, p=0.002). The treatment group showed a reduction in BNP at 1 year follow up compared to an increase in the control group (−567.87, 95% CI: −1288.90 to 153.15 in the treatment group versus 2004, 95% CI: 12.82 to 3995.45 in the control group, p<0.001). There was no significant difference from baseline and 1-year data between the control and treatment groups for the difference in echocardiographic parameters, native T1, T2. There was a significant reduction in the percentage of injected dose by 99Tc-DPD scintigraphy in treated patients at 1 year compared to baseline. Conclusions These findings provide the first compelling evidence of substantial cardiac amyloid regression in ATTR amyloidosis, as well as the potential for CMR to be used to track response in treated patients with ATTR cardiac amyloidosis. Combination therapy with transthyretin knock down and stabilizing agents may well be synergistic given enhanced stoichiometry of stabilizers in the face of much reduced plasma transthyretin concentration. Funding Acknowledgement Type of funding source: None

scholarly journals High Rate of Systolic Heart Failure in Patients with Hereditary Transthyretin Cardiac Amyloid

2021 ◽  
Vol 40 (4) ◽  
pp. S240
Author(s):  
S. Yalamanchili ◽  
M.T. Brown ◽  
E.A. Blank ◽  
M.A. Lyle ◽  
K.N. Bhatt
Keyword(s):  
Heart Failure ◽  
Systolic Heart Failure ◽  
High Rate ◽  
Cardiac Amyloid

Potential Cardiac Amyloid PET/CT Imaging Targets for Differentiating Immunoglobulin Light Chain From Transthyretin Amyloidosis

2021 ◽  
Vol 23 (7) ◽  
Author(s):  
Thomas Hellmut Schindler ◽  
Monica Sharma ◽  
Ines Valenta ◽  
Alessio Imperiale ◽  
Vasken Dilsizian
Keyword(s):  
Light Chain ◽  
Ct Imaging ◽  
Amyloid Pet ◽  
Immunoglobulin Light Chain ◽  
Transthyretin Amyloidosis ◽  
Cardiac Amyloid ◽  
Pet Ct

scholarly journals Amyloidosis with Cardiac Involvement: Identification, Characterization, and Management

2021 ◽  
Author(s):  
Faizi Jamal ◽  
Michael Rosenzweig
Keyword(s):  
Cardiac Amyloidosis ◽  
Systemic Disease ◽  
Treatment Options ◽  
Diagnostic Algorithm ◽  
Transthyretin Amyloidosis ◽  
Cardiac Amyloid ◽  
Medical Interventions ◽  
Light Chain Disease ◽  
Organ Response ◽  
New Treatment

Abstract Purpose of Review Amyloidosis is a protein deposition disease whereby a variety of precursor proteins form insoluble fibrils that deposit in tissues, causing organ dysfunction and, many times, death. Accurate characterization of the disease based on the nature of the precursor protein, organ involvement, and extent of disease is paramount to guide management. Cardiac amyloidosis is critical to understand because of its impact on prognosis and new treatment options available. Recent Findings New imaging methods have proven to be considerably valuable in the identification of cardiac amyloid infiltration. For treating clinicians, a diagnostic algorithm for patients with suspected amyloidosis with or without cardiomyopathy is shown to help classify disease and to direct appropriate genetic testing and management. For patients with light chain disease, recently introduced treatments adopted from multiple myeloma therapies have significantly extended progression-free and overall survival as well as organ response. In addition, new medical interventions are now available for those with transthyretin amyloidosis. Summary Although cardiac amyloidosis contributes significantly to the morbidity and mortality associated with systemic disease, new tools are available to assist with diagnosis, prognosis, and management.

scholarly journals T1 and T2 Mapping in Cardiology: “Mapping the Obscure Object of Desire”

Cardiology ◽  
2017 ◽  
Vol 138 (4) ◽  
pp. 207-217 ◽  
Author(s):  
Sophie Mavrogeni ◽  
Dimitris Apostolou ◽  
Panayiotis Argyriou ◽  
Stella Velitsista ◽  
Lilika Papa ◽  
...  
Keyword(s):  
Heart Failure ◽  
T1 Mapping ◽  
Clinical Decision Making ◽  
Volume Fraction ◽  
T2 Mapping ◽  
Extracellular Volume ◽  
Diffuse Fibrosis ◽  
Post Contrast ◽  
Cardiac Amyloid ◽  
Native T1

The increasing use of cardiovascular magnetic resonance (CMR) is based on its capability to perform biventricular function assessment and tissue characterization without radiation and with high reproducibility. The use of late gadolinium enhancement (LGE) gave the potential of non-invasive biopsy for fibrosis quantification. However, LGE is unable to detect diffuse myocardial disease. Native T1 mapping and extracellular volume fraction (ECV) provide knowledge about pathologies affecting both the myocardium and interstitium that is otherwise difficult to identify. Changes of myocardial native T1 reflect cardiac diseases (acute coronary syndromes, infarction, myocarditis, and diffuse fibrosis, all with high T1) and systemic diseases such as cardiac amyloid (high T1), Anderson-Fabry disease (low T1), and siderosis (low T1). The ECV, an index generated by native and post-contrast T1 mapping, measures the cellular and extracellular interstitial matrix (ECM) compartments. This myocyte-ECM dichotomy has important implications for identifying specific therapeutic targets of great value for heart failure treatment. On the other hand, T2 mapping is superior compared with myocardial T1 and ECM for assessing the activity of myocarditis in recent-onset heart failure. Although these indices can significantly affect the clinical decision making, multicentre studies and a community-wide approach (including MRI vendors, funding, software, contrast agent manufacturers, and clinicians) are still missing.

scholarly journals Genome silencer therapy leading to “regression” of cardiac amyloid load on cardiovascular magnetic resonance—a case report

2021 ◽  
Author(s):  
Anca Florian ◽  
Michael Bietenbeck ◽  
Anna Hüsing-Kabar ◽  
Matthias Schilling ◽  
Hartmut H Schmidt ◽  
...  
Keyword(s):  
Case Report ◽  
Early Death ◽  
Pathological Process ◽  
Left Ventricular ◽  
Disease Manifestation ◽  
Transthyretin Amyloidosis ◽  
Cardiac Amyloid ◽  
Amyloid Deposits ◽  
Short Period ◽  
Amyloid Load

Abstract Background Hereditary or variant transthyretin amyloidosis (ATTRv) is a progressive disease manifesting with neuropathy and/or cardiomyopathy. An early and accurate diagnosis of cardiac amyloidosis is a prerequisite for timely and appropriate patient management, including anti-amyloid therapies, as it is associated with heart failure, conduction disease and arrhythmias, leading to reduced quality of life and early death. Case Summary We present the case of an ATTRv male patient presenting with a mixed amyloidosis phenotype (neuropathy and cardiomyopathy). Cardiac disease manifestation comprised tachyarrhythmias (atrial fibrillation) and conduction abnormalities (AV-block) in addition to segmental left ventricular (LV) hypertrophy (septal wall) due to regionally pronounced amyloid deposits in the basal LV myocardium. Interestingly, by means of serial CMR studies, we were able to demonstrate an impressive and unexpected improvement of cardiomyopathy findings within a relatively short period-of-time after implementation of genome-silencer therapies. Discussion This is our second case report that showed ATTRv cardiomyopathy reversal under anti-amyloid therapy—documented by multiparametric CMR. Our findings support the hypothesis that amyloid infiltration leading to cardiomyopathy is not an irreversible pathological process—but rather a dynamic one, that cannot only be stopped but even reversed (to a certain degree) by currently emerging anti-amyloid therapies. Moreover, the role of serial multi-parametric CMR imaging for surveillance of cardiomyopathy dynamics under these therapies is nicely illustrated.

scholarly journals Diagnosis of Cardiac Amyloidosis Using Non-Invasive Technics

2021 ◽  
Author(s):  
Eva Strickler ◽  
Ernest Tsiaze ◽  
Gerrit Hellige ◽  
Dominik Zumstein ◽  
Dominik Waldmeier ◽  
...  
Keyword(s):  
Cardiac Amyloidosis ◽  
Al Amyloidosis ◽  
Definite Diagnosis ◽  
Diagnostic Features ◽  
Transthyretin Amyloidosis ◽  
Cardiac Amyloid ◽  
Non Invasive ◽  
Amyloid Accumulation ◽  
Clinically Significant ◽  
Multiorgan Disease

Amyloidosis is a rare multiorgan disease defined by a process of irreversible, extracellular accumulation of fibrillar proteins in the tissues, including the heart. Cardiac involvement is seen in most forms of amyloidosis, but it is frequently present and clinically significant in light chain (AL)-amyloidosis as well as transthyretin amyloidosis (ATTR). Cardiac amyloid accumulation leads to a restrictive filling pattern, which must be differentiated from other forms of restrictive and hypertrophic cardiomyopathies due to consequences for the treatment. Evolving knowledge of the disease has led to a definite diagnosis of the cardiac amyloidosis (CA) using non-invasive and low-risk diagnostic features, such as scintigraphy (gamma scan) and cardiovascular magnetic resonance (CMR) imaging using late gadolinium enhancement (LGE) and T1 mapping technics. The availability and diagnostic accuracy of these technics has reduced the need for cardiac biopsy. In the following chapter, we will describe common types of CA, the basic concepts, and updates of non-invasive diagnostic features.

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