Serial measurements of cardiac biomarkers in patients after allogeneic hematopoietic stem cell transplantation

<p>Abstract</p> <p>Background</p> <p>Previous therapy with anthracyclines (ANT) and conditioning regimen followed by hematopoietic stem cell transplantation (HSCT) represents a high risk for development of cardiotoxicity. The aim of this study was to assess subclinical myocardial damage after HSCT using echocardiography and cardiac biomarkers - high sensitive cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and to identify patients at risk of developing clinical cardiotoxicity.</p> <p>Patients and methods</p> <p>Thirty-seven patients who were treated with allogeneic HSCT for hematologic diseases at median age of 28 years at time of HSCT were studied. Conditioning regimen included either chemotherapy without total body irradiation (TBI) or combination of chemotherapy with TBI. Twenty-nine (78,3%) patients were pretreated with ANT therapy. Cardiac biomarkers were serially measured before conditioning regimen and at days 1, 14 and 30 after HSCT. Cardiac systolic and diastolic functions were assessed before conditioning regimen and 1 month after HSCT by echocardiography.</p> <p>Results</p> <p>The changes in plasma NT-proBNP and hs-cTnT levels during the 30 days following the HSCT were statistically significant (<it>P </it>< 0,01 v.s. <it>P </it>< 0,01). Persistent elevations of NT-proBNP and hs-cTnT simultaneously for a period exceeding 14 days after HSCT were found in 29,7% patients. Serum concentrations of cardiomarkers were significantly elevated in ANT group compared to non-ANT group. These observations were underscored by the echocardiographic studies which did reveal significant changes in systolic and diastolic parameters. Five of 37 (13,5%) patients developed clinical manifestation of cardiotoxicity.</p> <p>Conclusions</p> <p>Elevations in both cardiac biomarkers were found before clinical signs of cardiotoxicity developed. Persistent elevations in NT-pro-BNP and hs-cTnT concentrations simultaneously for a period exceeding 14 days might be used for identification of patients at risk of developing cardiotoxicity and requiring further cardiological follow up.</p

Cognitive impairment and biomarkers of gut microbial translocation in testicular germ cell tumor survivors

BackgroundSurvivors of testicular germ cell tumors (GCT) may suffer from late cognitive impairment. We hypothesized that disruption of intestinal barrier during chemotherapy and/or radiotherapy may be a contributing factor of cognitive dysfunction within the gut-blood-brain axis.MethodsGCT survivors (N = 142) from National Cancer Institute of Slovakia completed the Functional Assessment of Cancer Therapy Cognitive Function questionnaires during their annual follow-up visit at 9-year median (range 4-32). Biomarkers of gut microbial translocation and dysbiosis high mobility group box-1 (HMGB-1), lipopolysaccharide, d-lactate and sCD14 were measured from peripheral blood obtained during the same visit. Each questionnaire score was correlated with biomarkers. Survivors were treated with orchiectomy only (N = 17), cisplatin-based chemotherapy (N = 108), radiotherapy to the retroperitoneum (N = 11) or both (N = 6).ResultsGCT survivors with higher sCD14 (above median) had worse cognitive function perceived by others (CogOth domain) (mean ± SEM; 14.6 ± 0.25 vs 15.4 ± 0.25, p = 0.019), lower perceived cognitive abilities (CogPCA domain) (20.0 ± 0.74 vs 23.4 ± 0.73, p = 0.025) and lower overall cognitive function score (109.2 ± 0.74 vs 116.7 ± 1.90, p = 0.021). There were no significant cognitive declines associated with HMGB-1, d-lactate and lipopolysaccharide. Survivors treated with ≥ 400mg/m2 vs &lt; 400mg/m2 of cisplatin-based chemotherapy had a higher lipopolysaccharide (567.8 μg/L ± 42.7 vs 462.9 μg/L ± 51.9, (p = 0.03).ConclusionssCD14 is a marker of monocytic activation by lipopolysaccharide and may also serve as a promising biomarker of cognitive impairment in long-term cancer survivors. While chemotherapy and radiotherapy-induced intestinal injury may be the underlying mechanism, further research using animal models and larger patient cohorts are needed to explore the pathogenesis of cognitive impairment in GCT survivors within the gut-brain axis

QT prolongation due to targeted anticancer therapy

A growing number of targeted anticancer agents has shown the unexpected ability to induce QT interval prolongation. In addition, standard chemotherapeutics and a variety of conditions such as electrolyte abnormalities, endocrine disorders, cardiac diseases, nutritional disturbances and other factors may be associated with long QT syndrome in cancer patients. Prolongation of the QT interval can lead to life-threatening ventricular arrhythmias, including ‘torsade de pointes’ (TdP). The association between long QT interval and ventricular arrhythmias remains the subject of many controversies. The QT interval represents the time interval of both ventricular depolarization and repolarization. Not only abnormalities of ion channels, but also changes in the myocardial microarchitecture and other factors and disorders frequently seen in cancer patients may participate in its prolongation and potential risk of ventricular arrhythmias. The aim of this review was to summarize current knowledge about QT prolongation in cancer patients with the special focus on targeted therapy

Cardiac amyloidosis: a hidden cause of cardiovascular complications in oncology practice

Amyloidosis is rare, but known cause of heart failure, cardiomyopathy, coronary artery disease, disorders of cardiac conduction system and valvular damage. Disease often remains undetected until it reaches an advanced stage. Currently, we distinguish several types of amyloidosis. Cardiac amyloidosis may be caused by cancer, chronic inflammation, genetic factors and by aging related processes. Overproduction of amyloidogenic proteins by tumor cells has a key role in the pathogenesis of immunoglobulin light chain amyloidosis. Cardiovascular complications in patients with amyloidosis can be induced by insoluble deposits of misfolded proteins or by direct toxic effects of amyloidogenic molecules on cardiomyocytes and endothelial cells. In this review we focus mainly on pathophysiological mechanisms of cardiac amyloidosis, classification of cardiac amyloidosis types and their cardiovascular manifestations