Limits...
Cardiac amyloidosis responding to bortezomib: case report and review of literature.

Charaf E, Iskandar SB, Blevins A, Abi-Saleh B, Fahrig S - Curr Cardiol Rev (2009)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, University of South Alabama, Mobile, Alabama, USA.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

ECGs at14 and 24-month of follow-up, showing progressive resolution of microvoltage previously seen on limb leads.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2822146&req=5

Figure 4: ECGs at14 and 24-month of follow-up, showing progressive resolution of microvoltage previously seen on limb leads.

Mentions: The patient was deemed ineligible for stem cell transplantation. Chemotherapy targeting kappa-chain amyloidosis was initiated. Eight cycles of Melphalan and high dose of Dexamethasone were administered. After several months of therapy, this regimen has failed to improve our patient’s performance status, ejection fraction (35%) or reduce ventricular wall thickness. A trial of Thalidomide was initiated but ended quickly because of significant intolerance and the development of deep venous thrombosis. Bortezomib was then started at a dose of 1.3 mg/ m2 for eight cycles over 5 months. Like other cytotoxic agents traditionally used in the treatment of AL amyloidosis, bortezomib is know to target neoplastic cells and enhance their apoptosis through different mechanisms as detailed later in our review. The end result will be a reduction of the production and burden of amyloidogenic proteins, minimizing their deposition in various tissues including the myocardium. This regimen was well tolerated and no major side effects were observed. After 12 weeks of treatment, the patient reported a significant improvement in his functional capacity, exercise tolerance, and significant improvement of his exertional dyspnea and chest discomfort. The clinical improvement correlated with the disappearance of monoclonal spikes on serum and urine electrophoresis with a significant reduction in serum Kappa and Lambda light chains concentration. His follow-up electrocardiogram is shown below (Fig. 4). A follow-up echocardiography showed a significant regression of amyloid myocardial infiltration, decreased interventricular septum and posterior wall thickness from 1.9 to 1.3 cm, decreased left atrial diameter from 5.1 to 4.7 cm, and improvement of left ventricular ejection fraction from 35% to 55%. Until last seen in his scheduled appointment, the patient remained in good status and will continue to follow at our facility.


Cardiac amyloidosis responding to bortezomib: case report and review of literature.

Charaf E, Iskandar SB, Blevins A, Abi-Saleh B, Fahrig S - Curr Cardiol Rev (2009)

ECGs at14 and 24-month of follow-up, showing progressive resolution of microvoltage previously seen on limb leads.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2822146&req=5

Figure 4: ECGs at14 and 24-month of follow-up, showing progressive resolution of microvoltage previously seen on limb leads.
Mentions: The patient was deemed ineligible for stem cell transplantation. Chemotherapy targeting kappa-chain amyloidosis was initiated. Eight cycles of Melphalan and high dose of Dexamethasone were administered. After several months of therapy, this regimen has failed to improve our patient’s performance status, ejection fraction (35%) or reduce ventricular wall thickness. A trial of Thalidomide was initiated but ended quickly because of significant intolerance and the development of deep venous thrombosis. Bortezomib was then started at a dose of 1.3 mg/ m2 for eight cycles over 5 months. Like other cytotoxic agents traditionally used in the treatment of AL amyloidosis, bortezomib is know to target neoplastic cells and enhance their apoptosis through different mechanisms as detailed later in our review. The end result will be a reduction of the production and burden of amyloidogenic proteins, minimizing their deposition in various tissues including the myocardium. This regimen was well tolerated and no major side effects were observed. After 12 weeks of treatment, the patient reported a significant improvement in his functional capacity, exercise tolerance, and significant improvement of his exertional dyspnea and chest discomfort. The clinical improvement correlated with the disappearance of monoclonal spikes on serum and urine electrophoresis with a significant reduction in serum Kappa and Lambda light chains concentration. His follow-up electrocardiogram is shown below (Fig. 4). A follow-up echocardiography showed a significant regression of amyloid myocardial infiltration, decreased interventricular septum and posterior wall thickness from 1.9 to 1.3 cm, decreased left atrial diameter from 5.1 to 4.7 cm, and improvement of left ventricular ejection fraction from 35% to 55%. Until last seen in his scheduled appointment, the patient remained in good status and will continue to follow at our facility.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, University of South Alabama, Mobile, Alabama, USA.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus