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.

scholarly journals AL-amyloidosis with cardiac involvement. Diagnostic capabilities of non-invasive methods

2021 ◽  
Vol 93 (4) ◽  
pp. 487-496
Author(s):  
Alexandra Ya. Gudkova ◽  
Sergei V. Lapekin ◽  
Tinatin G. Bezhanishvili ◽  
Maria A. Trukshina ◽  
Victoria G. Davydova ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Cardiac Amyloidosis ◽  
Cardiac Involvement ◽  
Clinical Course ◽  
Al Amyloidosis ◽  
Transthyretin Amyloidosis ◽  
Non Invasive ◽  
Amyloid Cardiomyopathy ◽  
Diagnostic Capabilities ◽  
Invasive Diagnostics

There are presented the literature data and a description of the clinical course of the disease in isolated/predominant cardiac amyloidosis. Amyloid cardiomyopathy is the most common phenocopy of hypertrophic cardiomyopathy. The modern possibilities of non-invasive diagnostics using osteoscintigraphy for the differential diagnosis between amyloid cardiomyopathy caused by AL- and transthyretin amyloidosis are described in detail.

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 Multimodality imaging can shift the clinical approach and prognosis of a patient: from heart failure and angina to cardiac amyloidosis

2021 ◽  
Vol 31 (1) ◽  
pp. 103-110
Author(s):  
Alexandra Maria Chitroceanu ◽  
Alina Ioana Nicula ◽  
Roxana Cristina Rimbas ◽  
Mihaela Andreescu ◽  
Cristina Popp ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Amyloidosis ◽  
Multimodality Imaging ◽  
Clinical Status ◽  
Decompensated Heart Failure ◽  
Response To Therapy ◽  
Al Amyloidosis ◽  
Clinical Approach ◽  
Non Invasive ◽  
Life Threatening

AL (light chain) amyloidosis is a life threatening disease. Untreated patients with involvement of the heart, a condition known as cardiac amyloidosis (CA), tend to have the most rapid disease progression and worst prognosis. Therefore, it is essential to early recognize the signs of symptoms of CA, and to identify the affected individuals with readily available non-invasive tests, as timely therapy can prolong life. Different imaging tests are used to diagnose and stratify the risk of the disease noninvasively, and to follow-up of the disease course and response to therapy. In this light, we present a case of a woman with cardiovascular risk factors, initially admitted for typical angina and decompensated heart failure (HF), who was later diagnosed with AL amyloidosis with cardiac involvement, by using multimodality imaging assessment in a step-by-step fashion. This changed completely the prognosis of the patient. Timely chemotherapy and stem cell transplantation led to an improvement in clinical status, biomarkers, and in a regression of amyloid myocardial infi ltration showed by imaging.

scholarly journals Outcomes in patients with cardiac amyloidosis and implantable cardioverter-defibrillator

EP Europace ◽  
2020 ◽  
Vol 22 (8) ◽  
pp. 1216-1223
Author(s):  
Eun-Jeong Kim ◽  
Benjamin B Holmes ◽  
Shi Huang ◽  
Ricardo Lugo ◽  
Asad Al Aboud ◽  
...  
Keyword(s):  
Primary Prevention ◽  
Implantable Cardioverter Defibrillator ◽  
Cardiac Amyloidosis ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Al Amyloidosis ◽  
Transthyretin Amyloidosis ◽  
Ventricular Ejection Fraction ◽  
Cardioverter Defibrillator ◽  
Significant Difference

Abstract Aims Cardiac amyloidosis (CA) is associated with increased mortality due to arrhythmias, heart failure, and electromechanical dissociation. However, the role of an implantable cardioverter-defibrillator (ICD) remains unclear. We conducted case-control study to assess survival in CA patients with and without a primary prevention ICD and compared outcomes to an age, sex, and device implant year-matched non-CA group with primary prevention ICD. Methods and results There were 91 subjects with CA [mean age= 71.2 ± 10.2, female 22.0%, 49 AL with Mayo Stage 2.9 ± 1.0, 41 transthyretin amyloidosis (ATTR), 1 other] followed by Vanderbilt Amyloidosis centre. Patients with ICD (n = 23) were compared with those without (n = 68) and a non-amyloid group with ICD (n = 46). All subjects with ICD had implantation for primary prevention. Mean left ventricular ejection fraction was 36.2% ± 14.4% in CA with ICD, 41.0% ± 10.6% in CA without ICD, and 33.5% ± 14.4% in non-CA patients. Over 3.5 ± 3.1 years, 6 (26.1%) CA, and 12 (26.1%) non-CA subjects received ICD therapies (P = 0.71). Patients with CA had a significantly higher mortality (43.9% vs. 17.4%, P = 0.002) compared with the non-CA group. Mean time from device implantation to death was 21.8 months in AL and 22.8 months in ATTR patients. There was no significant difference in mortality between CA patients who did and did not receive an ICD (39.0% vs. 46.0%, P = 0.59). Conclusions Despite comparable event rates patients with CA had a significantly higher mortality and ICDs were not associated with longer survival. With the emergence of effective therapy for AL amyloidosis, further study of ICD is needed in this group.

Diagnosis of Cardiac Transthyretin Amyloidosis by Technetium-99m Pyrophosphate Heart Scan, Confirmed by Genetic Mutations: Case Report

2021 ◽  
Vol 104 (11) ◽  
pp. 1843-1846
Keyword(s):  
Heart Failure ◽  
Case Report ◽  
Genetic Testing ◽  
Cardiac Amyloidosis ◽  
Abdominal Fat ◽  
Genetic Mutations ◽  
Fat Pad ◽  
Transthyretin Amyloidosis ◽  
Technetium 99M ◽  
Clinically Significant

Amyloid deposition in the myocardium can cause clinically significant heart failure, which is very difficult to diagnose. The present case reported presented a patient with heart failure, with suspected cause of cardiac amyloidosis, but abdominal fat pad and endomyocardial with Congo red stain biopsies were negative. Due to high suspicion of cardiac amyloidosis, a technetium-99m pyrophosphate (Tc-99m PYP) heart scan was done, which was revealed as strongly suggestive for cardiac transthyretin amyloidosis. So, the patient was sent for genetic testing, and a TTR gene mutation [c.148G>A (p.Val50Met)] was found. Keywords: Cardiac amyloidosis; Endomyocardial biopsy (EMB); Technetium-99m pyrophosphate (Tc-99m PYP) heart scan; Transthyretin amyloidosis (TTR)

Unfolding Cardiac Amyloidosis –From Pathophysiology to Cure

2019 ◽  
Vol 26 (16) ◽  
pp. 2865-2878 ◽  
Author(s):  
Klemens Ablasser ◽  
Nicolas Verheyen ◽  
Theresa Glantschnig ◽  
Giulio Agnetti ◽  
Peter P. Rainer
Keyword(s):  
Cardiac Disease ◽  
Cardiac Remodeling ◽  
Cardiac Amyloidosis ◽  
Amyloid Fibrils ◽  
Amyloid Deposition ◽  
Transthyretin Amyloidosis ◽  
Cardiac Amyloid ◽  
Amyloidogenic Proteins ◽  
Preclinical Trials ◽  
Current Therapies

Deposition of amyloidogenic proteins leading to the formation of amyloid fibrils in the myocardium causes cardiac amyloidosis. Although any form of systemic amyloidosis can affect the heart, light-chain (AL) or transthyretin amyloidosis (ATTR) account for the majority of diagnosed cardiac amyloid deposition. The extent of cardiac disease independently predicts mortality. Thus, the reversal of arrest of adverse cardiac remodeling is the target of current therapies. Here, we provide a condensed overview on the pathophysiology of AL and ATTR cardiac amyloidoses and describe treatments that are currently used or investigated in clinical or preclinical trials. We also briefly discuss acquired amyloid deposition in cardiovascular disease other than AL or ATTR.

Sequential heart and autologous stem cell transplantation for systemic AL amyloidosis

Blood ◽  
2006 ◽  
Vol 107 (3) ◽  
pp. 1227-1229 ◽  
Author(s):  
Julian D. Gillmore ◽  
Hugh J. Goodman ◽  
Helen J. Lachmann ◽  
Mark Offer ◽  
Ashutosh D. Wechalekar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Heart Transplantation ◽  
Cell Transplantation ◽  
Plasma Cell Dyscrasia ◽  
Al Amyloidosis ◽  
Cardiac Amyloid ◽  
Kaplan Meier ◽  
Amyloid Accumulation ◽  
Related Mortality

AbstractExtensive cardiac amyloid deposition in systemic AL amyloidosis is associated with a grave prognosis. Heart transplantation is rarely performed because of the systemic and progressive nature of the disease. Patients with severe cardiac amyloid infiltration are ineligible for the preferred treatment of melphalan chemotherapy with stem cell transplantation (SCT) rescue because of the high risk for treatment-related mortality. Heart transplantation followed by SCT was performed in 5 patients with AL amyloidosis and predominant cardiomyopathy. Patients were followed up for a median of 95 months (range, 37-118 months) from diagnosis. At censor, 3 of 5 patients were well without evidence of intracardiac or extracardiac amyloid accumulation, and median overall survival by Kaplan-Meier estimate was not reached. Two patients died of progressive amyloidosis 33 and 90 months after heart transplantation after relapse of their underlying plasma cell dyscrasia. Heart transplantation followed by SCT is feasible in selected patients with cardiac AL amyloidosis and may confer substantial survival benefit.

scholarly journals Cardiac Amyloidosis

2021 ◽  
Author(s):  
Csilla Andrea Eötvös ◽  
Giorgia Pastiu ◽  
Iulia Zehan ◽  
Cerasela Goidescu ◽  
Roxana Chiorescu ◽  
...  
Keyword(s):  
Protein Misfolding ◽  
Cardiac Amyloidosis ◽  
Clinical Laboratory ◽  
Specific Treatment ◽  
Restrictive Cardiomyopathy ◽  
Al Amyloidosis ◽  
Transthyretin Amyloidosis ◽  
Immunoglobulin Light Chain Amyloidosis ◽  
The Many ◽  
Definition Of

Amyloidosis represents a heterogeneous group of disorders caused by amyloid fibril deposition in the extracellular space in different organs. Among the many types of amyloidosis cardiac involvement occurs almost exclusively with immunoglobulin light chain amyloidosis (AL amyloidosis) or transthyretin amyloidosis (ATTR amyloidosis). When present cardiac amyloidosis (CA) has a significant impact on disease prognosis. The typical clinical presentation in CA is that of a restrictive cardiomyopathy. Clinical suspicion of CA is based on clinical, laboratory and electrocardiographic findings. The diagnosis is confirmed using echocardiography, cardiac magnetic resonance imaging, biopsy, and/or bone scintigraphy. A precise definition of amyloidosis type is essential for choosing the specific treatment for this condition. Treatment of CA has two components: general treatment of congestive HF, and specific treatment of the underlying protein misfolding disorder.

Cardiac Followed by Autologous Stem Cell Transplantation for Systemic AL Amyloidosis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1158-1158
Author(s):  
J. D. Gillmore ◽  
A. D. Wechalekar ◽  
H. J.B. Goodmam ◽  
H. J. Lachmann ◽  
M. Offer ◽  
...  
Keyword(s):  
Light Chain ◽  
Cardiac Transplantation ◽  
Light Chains ◽  
Al Amyloidosis ◽  
Cardiac Transplant ◽  
Serum Free ◽  
Cardiac Amyloid ◽  
Amyloid Accumulation ◽  
Haematological Remission ◽  
The Uk

Abstract The prognosis for AL amyloidosis with conventional treatment is very poor. Treatment with high dose melphalan with stem cell rescue (SCT) may offer the best chance of haematological remission and arresting amyloid accumulation. However, patients with significant clinically apparent cardiac amyloid are not eligible for SCT due to unacceptably high treatment-related mortality. Cardiac transplantation is controversial due to the systemic and progressive nature of the disease. We report the UK experience of this combined approach in patients with predominant cardiac AL amyloidosis. Cardiac transplantation followed by SCT was undertaken in 5 patients with histologically confirmed AL amyloidosis who presented to the UK National Amyloidosis Centre. Cardiac assessment included clinical evaluation, ECG and echocardiographic studies, and measurement of NT-proBNP (retrospectively). The median age at diagnosis of amyloid was 53 years (range 38–59). The median time from diagnosis to cardiac transplantation was 4 months (range 2–9). All patients had NYHA class IV heart failure and advanced cardiac amyloidosis by echocardiographic criteria. There was no evidence of extra-cardiac amyloid related organ dysfunction. Median interventricular septal (IVS) and left ventricular posterior wall (LVPW) thicknesses were 17 mm (IVS range 15–19, LVPW range 15–18). 4 patients had a conventionally detectable serum M protein, 3 had light chains in the urine while all had abnormal serum free light chains (sFLC) (kappa light chain excess in 2 and lambda light chain excess in 3). 2/5 patients received melphalan 25mg/m2 prior to cardiac transplant. The cardiac transplant was uncomplicated in 3 patients while 1 had a single episode to tonic clonic seizures (cyclosporine induced) and 1 had reversible acute renal failure (ARF) with a median post operative stay of 24 days (range 14–30). Acute rejection occurred on a single occasion in 2 patients (ISHLT grade 2 or 3A) and responded to intravenous methylprednisolone. The median time from cardiac transplantation to SCT was 13 months (range 10–24). At the time of SCT, there was no echocardiographically detectable amyloid in any of the cardiac grafts though all patients had clinical and/or SAP scintigraphic evidence of progressive extra-cardiac amyloid. All patients received melphalan 140mg/m2 as transplant conditioning. The post transplant course was complicated by a liposomal amphoterecin responsive fungal chest infection and ARF in 1 patient each. None of the patients had any cardiac problems during the SCT. 4/5 patients had a ≥50% reduction in serum free light chain production. The median follow-up is now 95 (range, 37–118) and 90 (range, 33–114) months from diagnosis of amyloidosis and cardiac transplantation respectively. Three of 5 patients are alive, in haematological remission with no evidence of intra or extra-cardiac amyloid accumulation. Median overall survival by Kaplan-Meier estimate has not been reached. Of the 2 patients who died, 1 patient had a poor response to SCT while the other patient relapsed 80 months post SCT. Both had progressive amyloid deposition including echocardiographic evidence of amyloid in the transplanted heart. In summary, cardiac transplantation followed by SCT is feasible in carefully selected patients with predominantly cardiac AL amyloidosis and may be associated with prolonged survival.

Abnormal NT-ProBNP in AL Amyloidosis Patients without Cardiac Involvement at Diagnosis - A Predictor of Subsequent Cardiac Involvement.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1500-1500
Author(s):  
Ashutosh D. Wechalekar ◽  
Helen J. Lachmann ◽  
Julian D. Gillmore ◽  
Philip N. Hawkins
Keyword(s):  
Cardiac Amyloidosis ◽  
Cardiac Involvement ◽  
Myocardial Dysfunction ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Al Amyloidosis ◽  
International Consensus ◽  
Cardiac Amyloid ◽  
Significant Difference

Abstract Cardiac involvement in AL amyloidosis is associated with a poor prognosis and greatly increased treatment related morbidity and mortality, and regression of cardiac amyloid deposits is extraordinarily slow following chemotherapy that suppresses the underlying aberrant light chain production. Diagnosis of cardiac amyloidosis is normally made by echocardiography, by which time significant diastolic dysfunction has usually developed. Atrial natriuretic peptides (ANP, BNP and its N-terminal fragment NT-ProBNP) are useful in early diagnosis of myocardial dysfunction. Serum NT-ProBNP concentration has been reported to be a promising marker of cardiac dysfunction in AL amyloidosis, and patients with normal NT-ProBNP values at diagnosis have superior outcomes. We report here the outcome of patients attending the UK National Amyloidosis Centre (NAC) who had elevated NT-ProBNP at diagnosis of AL amyloidosis but who did not have accompanying evidence of cardiac involvement using conventional consensus criteria. To exclude the confounding effect of renal failure which is associated with substantial elevation of NT-ProBNP, we studied patients with serum creatinine <150 μmol/L and creatinine clearance of >50ml/min at diagnosis in whom there was less than 10% change in renal function after treatment. AL type amyloidosis was confirmed in all patients histologically with corroborating genetic studies to robustly exclude hereditary amyloidosis as indicated. Organ involvement and responses/progression were defined according to recent international consensus criteria (Gertz et al 2005). 102 patients who had no evidence of cardiac involvement by these conventional parameters and who otherwise conformed with our study criteria were identified. Median creatinine was 87 μmol/L (44–128), albumin 33g/L (10–65), bilirubin 7 μmol/L (1–65) and alkaline phosphatase 89 units/L (36–2649). The median interventricular septal and left ventricular posterior wall thickness was 9 mm (7–11 mm). 62 (61%) patients had NT-ProBNP ≤ 35pMol/L at diagnosis while 40 (39%) had NT-ProBNP of >35 pMol/L. There was no significant difference in the baseline characteristics of either group. 5 patients in each group did not respond to the initial chemotherapy (p=0.46). With median follow-up of 60 months, 19/40 (47%) of patients with NT-ProBNP >35pMol/L at diagnosis developed evidence of cardiac involvement compared to only 6/62 (10%) of whose baseline NT-ProBNP was ≤ 35 pMol/L (p<0.001). The Kaplan-Meier estimated median overall survival has not been reached for either group but the estimated 7 year survival was significantly better in the group with NT-ProBNP of ≤35pMol/L compared to those with greater values (92% vs. 82%, p=0.03). In conclusion, these preliminary findings suggest that patients who have elevated NT-ProBNP concentration but no conventional evidence of cardiac involvement at diagnosis of AL amyloid appear to be at greater risk of developing cardiac amyloidosis during follow-up, and have a poorer prognosis. It reasonable to speculate that such patients have early cardiac involvement at diagnosis that cannot be identified by conventional non-invasive methods, and that their risk of subsequently developing clinically significant cardiac amyloidosis may be reduced by striving to achieve complete remission of their underling clonal plasma cell disease.

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