melphalan and Ventricular-Dysfunction--Left

To determine whether echocardiographic longitudinal systolic strain (LS) parameters identify short-term improvement following chemotherapy for light-chain (AL) cardiac amyloidosis (CA). Among patients with CA, standard echocardiographic measures are commonly unchanged at 1 year following successful chemotherapy, despite observed reductions in cardiac biomarkers.. We retrospectively identified 61 patients with AL-CA treated with high-dose melphalan or bortezomib-based regimens. Patients were classified by hematologic response at 1 year into two groups: complete response (CR; n = 18, or 30%) or non-CR (non-CR; n = 43, or 70%), and followed for 20 months. Serum free light chains (FLC), B-type natriuretic peptide (BNP), troponin I (TnI), and echocardiography including LS, were acquired at baseline and 1 year. Seven patients died (11.5%), all in the non-CR group (P < 0.01). At 1 year, while reductions were observed in BNP (44% CR, 18% non-CR) and FLC (94% CR, 73% non-CR), both P < 0.05 from baseline, there were no differences in wall thickness, EF, or diastolic function in either group. LS improved only in the CR group with notable improvement in apical to basal strain ratio (P < 0.05). Strain improvement and BNP reduction were correlated (R = 0.6, P < 0.01). Baseline global LS < -10.2% was associated with survival and proved superior to BNP and TnI. The addition of global LS to biomarkers identified the patients at highest risk of mortality.. These data suggest that LS is a sensitive measure of pre-treatment cardiac functional impairment in AL-CA, can predict survival over and above that of cardiac biomarkers, and detect early cardiac functional improvement following chemotherapy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Bortezomib; Boston; Cardiomyopathies; Cohort Studies; Echocardiography, Doppler, Color; Female; Follow-Up Studies; Heart Function Tests; Hospitals, University; Humans; Immunoglobulin Light-chain Amyloidosis; Kaplan-Meier Estimate; Male; Melphalan; Middle Aged; Prognosis; Retrospective Studies; ROC Curve; Sensitivity and Specificity; Survival Analysis; Treatment Outcome; Ventricular Dysfunction, Left

We experienced the case of a 67-year-old man with refractory heart failure. He presented with dyspnea and progressive pitting edema of the lower limbs. Diuretics were insufficient to improve his symptoms. Cardiac catheterization demonstrated pulmonary hypertension. Additional examinations confirmed polyneuropathy, organomegaly, endocrinopathy and monoclonal gammopathy. The plasma vascular endothelial growth factor (VEGF) level was 1,340 pg/mL. The patient was diagnosed with Crow-Fukase (POEMS) syndrome. Echocardiography detected left ventricular hypertrophy and diastolic dysfunction. Polysomnography demonstrated severe sleep-disordered breathing. We herein describe a case of pulmonary hypertension with Crow-Fukase syndrome accompanied by left ventricular diastolic dysfunction and sleep-disordered breathing.

Topics: Aged; Dexamethasone; Diuretics; Drug Resistance; Edema; Furosemide; Heart Failure; Humans; Hypertension, Pulmonary; Hypertrophy, Left Ventricular; Male; Melphalan; POEMS Syndrome; Polysomnography; Prednisolone; Pulmonary Wedge Pressure; Sleep Apnea Syndromes; Thalidomide; Ultrasonography; Vascular Endothelial Growth Factor A; Ventricular Dysfunction, Left

Cardiac dysfunction is a well-recognized complication of light chain amyloidosis (AL). Autologous stem cell transplant (auto-SCT) has emerged as a successful treatment modality for AL patients. In this study, we examined the effect of clonal immunoglobulin light chain genes (VL), which encodes the immunoglobulin light chain protein that ultimately forms amyloid, on cardiac function, in the context of auto-SCT and its impact on overall survival.. Longitudinal Doppler myocardial imaging parameters along with cardiac biomarkers were used to assess for cardiac function pre and post auto-SCT.. VL gene analysis revealed that Vl genes, in particular VlVI, were associated with worse cardiac function parameters than Vk genes. Clonal VL genes appeared to have an impact on left ventricular (LV) function post-transplant and also influenced mortality, with specific VL gene families associated with lower survival. Another key predictor of mortality in this report was change in tricuspid regurgitant flow velocity following auto-SCT. Correlations were also observed between systolic strain rate, systolic strain and VL genes associated with amyloid formation.. Clonal VL gene usage influences global cardiac function in AL, with patients having VlVI and VlII-III-associated amyloid more severely affected than those having Vk or VlI amyloid. Pulsed wave tissue Doppler imaging along with immunoglobulin gene analysis offers novel insights into prediction of mortality and cardiac dysfunction in AL after auto-SCT.

Topics: Amyloidosis; Antineoplastic Agents, Alkylating; Biomarkers; Echocardiography, Doppler; Female; Genes, Immunoglobulin; Humans; Immunoglobulin Light Chains; Immunoglobulin Variable Region; Male; Melphalan; Middle Aged; Peripheral Blood Stem Cell Transplantation; Proportional Hazards Models; Prospective Studies; Reproducibility of Results; Sensitivity and Specificity; Statistics, Nonparametric; Transplantation, Autologous; Treatment Outcome; Ventricular Dysfunction, Left

Cardiotoxicity has rarely been reported as a complication of melphalan or fludarabine administration as single agents. Recently, melphalan and fludarabine have been used in combination as non-myeloablative conditioning chemotherapy prior to allogeneic stem cell transplantation. We have observed the development of severe left ventricular failure in three of 21 patients treated with this combination. Cardiotoxicity in this context has not previously been reported and has implications for the assessment, monitoring and treatment of patients undergoing pre-transplant conditioning with melphalan and fludarabine.

Topics: Acute Disease; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Transplantation Conditioning; Transplantation, Homologous; Ventricular Dysfunction, Left; Vidarabine