Vascular Functions in Myeloma Patients During Anti-tumor Therapy

Treatment options for multiple myeloma have increased significantly over the last years with the approval of immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). These therapies have markedly improved overall survival for these patients to a median of 5-7 years. Due to the advanced age, the myeloma patient collective has a high prevalence of pre-existing cardiovascular comorbidities. In addition, the primary disease process contributes to cardiovascular complications. With the beginning of anti-tumor therapy, an increased incidence of cardiovascular complications in myeloma patients can be determined. This includes hypertension, left ventricular dysfunction, heart failure and both arterial and venous thromboembolic events. The detailed mechanism by which proteasome inhibitors and immunomodulatory agents lead to increased cardiovascular events is not established at this time. Endothelial dysfunction, as a possible mechanism of cardiovascular toxicity, is difficult to assess. Flow-mediated dilation (FMD) is an noninvasive method to measure endothelial function by assessing the change in the vasodilatative reserve of the brachial artery. Several independent recent investigations implicate that vascular (endothelial) dysfunction precedes hypertension and heart failure. This has been related to a reduced level of metabolites of the l-arginine-nitric oxide (NO) signaling pathway. Hypothesis: 1. Anti-myeloma therapy exert vascular toxicity by limiting endothelial function. Endothelial function, assessed by the change in the vasodilatative reserve of the brachial artery (flow-mediated dilation = FMD) decreases after myeloma therapy. 2. Patients with multiple myeloma have a limited endothelial function compared to a healthy control group. A total of 40 myeloma patients will be examined. Measurements will be taken at baseline, 1 month and 6 month after myeloma therapy. Patients should not have received chemotherapy for at least 3 months. Furthermore a healthy sex- and age-matched control group will be examined.

Sex

All

Minimum age

18 Years

Included in the study are myeloma patients with planned bortezomib, carfilzomib and lenalidomide-based chemotherapy and 20 subjects from a healthy normal population.

Inclusion Criteria:

* Age ≥ 18 years
* written consent

Exclusion Criteria:

* Severe pulmonary, valvular, or congenital heart disease with clinical dyspnoea symptoms
* Life expectancy less than 6 months
* Unstable angina pectoris or indication for coronary revascularization
* Valvular disease (aortic valve and mitral regurgitation greater than moderate, and aortic valve or mitral valve stenosis greater than moderate)
* Atrial fibrillation or flutter
* Chronic renal insufficiency (Cockcroft-Gault GFR \<30 mL / min)
* Severe cirrhosis (Child-Pugh B and C)
* Current or future indication for therapy with organic nitrates
* Leading non-cardiac cause of clinical dyspnea symptoms, such as high-grade obesity or lung disease in need of glucocorticoid therapy or oxygen therapy
* Other cause of clinical dyspnea symptoms, such as high-grade obesity or lung disease with need for glucocorticoid therapy or oxygen therapy