Management Of Cardiac Amyloidosis Research Articles

A Focused Review on the Pathophysiology, Diagnosis, and Management of Cardiac Amyloidosis

Amyloidosis is a systemic disorder that results from abnormal protein metabolism, producing amyloid fibrils that are subsequently deposited within vital organs. Cardiac involvement is typically associated with the specific subtypes of immunoglobulin lightchain, transthyretin, secondary amyloidosis, and dialysis-related amyloidosis. The hallmark of cardiac amyloidosis is the development of restrictive cardiomyopathy and heart failure, usually with a preserved left ventricular ejection fraction. The diagnosis is based on the integration of clinical signs and symptoms, echocardiography, cardiac magnetic resonance imaging, nuclear scintigraphy, electrocardiography, and cardiac biomarkers. Traditionally, management of heart failure symptoms and prevention of heart failure exacerbations have been the cornerstones of therapy. However, various treatments are currently under investigation that aim to eliminate or neutralize the underlying amyloidogenic substrate. Herein, we provide a focused review and discussion of the cardiovascular manifestations, epidemiologic and clinical characteristics, diagnostic modalities, and treatment strategies of cardiac amyloidosis.

Emerging Advances in the Management of Cardiac Amyloidosis

Amyloidosis is a disease in which proteins misfold, aggregate into fibrils, and deposit extracellularly disrupting organ architecture and function. There are two main types which affect the heart: light chain (AL) amyloidosis and transthyretin cardiac amyloidosis (ATTR). There is a misconception that cardiac amyloidosis has no effective treatment options. However, over the past decade, there has been extensive research and drug development. Outcomes are improving in AL amyloidosis with evolving chemotherapeutic regimens and novel monoclonal antibodies. In ATTR, therapies that decrease protein production, prevent dissociation, and promote clearance have the potential to slow or even halt a disease which is uniformly fatal. Selected patients may be candidates for heart and/or stem cell transplant and should be promptly referred to an experienced amyloid program. Herein, we discuss the emerging advances for the treatment of cardiac amyloidosis.

Cardiac amyloidosis: where are we today?

Systemic amyloidosis is generally considered to be rare, but the heart is frequently involved and is a major determinant of prognosis. New diagnostic imaging methods have recently been developed with the capacity to enhance the accuracy of diagnosis, which will be ever more important with the variety of new treatments on the near horizon. Most cases of cardiac amyloidosis are of either monoclonal immunoglobulin light chain (AL) type, which can occur at any age from young adulthood onwards, or transthyretin (ATTR) type, which can be acquired in elderly individuals or inherited at a younger age. Cardiac involvement is the most serious manifestation of AL amyloidosis, and serum cardiac biomarkers have proved to be of great value in staging disease severity and response to an ever increasing array of chemotherapy agents. Cardiac involvement is the dominant manifestation of nonhereditary ATTR amyloidosis, also known as senile cardiac amyloidosis, the prevalence of which is not known but is probably much greater than currently recognized. A genetic variant in the gene for transthyretin (TTR), which is present in 3-4% of African Americans and probably a similar proportion of black individuals of African descent generally, appears to be associated with increased susceptibility to developing cardiac ATTR amyloidosis in older age. Several novel therapies are in the advanced stages of development for ATTR amyloidosis including TTR protein stabilizers and RNA inhibitors that greatly diminish TTR production. Here, we will review recent developments in the diagnosis and management of cardiac amyloidosis.

Echocardiographic assessment of the cardiac amyloidoses.

Cardiac amyloidosis is a cardiomyopathy characterized by increased left ventricular (LV) wall thickness and normal or decreased LV cavity size. Congestive heart failure in cardiac amyloidosis is generally considered a predominantly diastolic phenomenon, with systolic dysfunction only occurring in late-stage disease. Echocardiography is a noninvasive, reproducible method of assessing cardiac features and function in cardiac amyloidosis, and some echocardiographic indices are prognostic for the amyloidoses, with M-mode and 2-dimensional echocardiography able to detect increased LV wall thickness. Moreover, Doppler flow measurements can incrementally assess diastolic LV dysfunction, which is characteristic of cardiac amyloidosis, and provide important prognostic information. Additionally, tissue Doppler imaging can detect subtle changes in both systolic and diastolic LV function, which cannot be detected by Doppler flow measurements, and LV longitudinal strain assessed by color tissue Doppler and speckle tracking echocardiography can provide more accurate LV functional and prognostic information than tissue Doppler imaging. This review describes the advances in echocardiography and its crucial role in the diagnosis and management of cardiac amyloidosis.

Recent Advances in the Diagnosis and Management of Cardiac Amyloidosis

The heart is commonly involved in various forms of amyloidosis and cardiomyopathy is a major cause of morbidity and mortality in these patients. Diagnosis of cardiac amyloidosis is often delayed due to nonspecific presenting symptoms and failure to recognize early signs of amyloid heart disease on routine cardiac imaging. Treatment of cardiac amyloidosis depends upon the type of amyloid protein. Systemic chemotherapy with or without stem cell transplantation is used to treat immunoglobulin-related amyloidosis and liver transplantation is used for familial transthyretin amyloidosis in select patients. Clinical trials with siRNA for the treatment of transthyretin amyloid cardiomyopathies and amyloid protein stabilizers are ongoing. Prognosis depends on the type of amyloid protein with poorer outcomes noted in immunoglobulin light-chain amyloidosis. Supportive care forms the cornerstone of management and advancements in cardiac imaging and proteomics are expected to positively impact our ability to diagnose, prognosticate and treat cardiac amyloidosis.

Current Trends in Diagnosis and Management of Cardiac Amyloidosis

Amyloidosis is a rare disease in which insoluble extracellular protein fibrils in β-pleated sheets infiltrate multiple organs, causing organ dysfunction and failure. Amyloidoses are generally classified into light chain or primary systemic amyloidosis, hereditary amyloidosis (most commonly, transthyretin amyloidosis), senile systemic amyloidosis, secondary amyloidosis, and isolated atrial amyloidosis. At least 100 different amyloidogenic proteins have been identified in humans and can be differentiated by mass spectroscopy after laser capture microdissection and genetic testing. Organ involvement can include kidneys, skin, blood vessels, central and peripheral nervous systems, lungs, liver, intestines, and heart. Developments in noninvasive techniques are facilitating earlier and more accurate diagnosis. Management depends on the specific disease type, thus early and accurate diagnosis is imperative. Prognosis generally correlates with degree of cardiac involvement but varies widely with specific amyloid protein type. New treatment strategies involving chemotherapy and organ transplantation are improving survival, but prognosis is guarded.

Heart Transplantation and End-Stage Cardiac Amyloidosis: A Review and Approach to Evaluation and Management

Cardiac amyloidosis is one of the most common of the infiltrative cardiomyopathies and is associated with a poor prognosis. The extent of cardiac involvement with amyloid deposition is an important determinant of treatment options and is the major determinant of outcome in patients with amyloidosis. Several small case series with sequential orthotopic heart transplantation and autologous stem cell transplant have demonstrated an improvement in post-transplant outcome and have revived enthusiasm about heart transplantation for patients with end-stage heart failure due to AL amyloidosis. The purpose of this review is to summarize the evaluation and management of cardiac amyloidosis and to provide our single-center experience with end-stage heart failure due to AL amyloidosis treated with heart transplantation followed by an autologous stem cell transplant.

Cardiac Amyloidosis Responding to Bortezomib: Case Report and Review of Literature

We report a case of a 53-year old patient with symptoms of congestive heart failure in whom a restrictive cardiomyopathy and a kappa-chain monoclonal gammopahty were diagnosed. Treatment with eight cycles of Bortezomib, a proteasome inhibitor, resulted in a significant regression of myocardial amyloid deposition and a notable clinical and hemodynamic improvement. Over the last few years, the management of cardiac amyloidosis has taken advantage of many of the advances of the chemotherapeutic regimens, as well as the wider availability of stem cell transplantation. The management of cardiac amyloidosis is also expected to evolve and improve with the better understanding of the specific mechanisms of amyloidogenesis and myocardial deposition. This will probably make certain molecules targeting specific sites in this process, as potentially effective and minimally toxic compared therapy with the currently used ones. In this article, we describe one of the first reported cases of cardiac amyloidosis, successfully treated with Bortezomib. We describe and discuss the mechanisms of action of Bortezomib and provide a detailed review of cardiac amyloidosis, from pathophysiology to diagnosis and treatment.

Cardiac amyloidosis — Experience in a tertiary cardiac referral centre

Amyloidosis is an uncommon systemic disease characterized by deposition of insoluble fibrillar protein in different organs and the prognosis is poor if the heart is involved. Experience with management of cardiac amyloidosis is difficult because of its rare occurrence, late presentation and ineffective treatment. Since 1995, we have encountered and prospectively followed up 16 cases of cardiac amyloidosis in our cardiac centre. We believe this is the largest series of cardiac amyloidosis reported in Chinese patients. The 1-year, 3-year and 5-year survival rates were 40%, 25% and 17%, respectively. The major cause of death was cardiac-related. Those patients with overt heart failure or with untreated amyloidosis had a dismal prognosis (mean survival of 2.2 months and 3.5 months, respectively). Those who received specific treatment for the underlying amyloidosis had a better outcome with an average survival of 33.4 months.