Early Cardiotoxicity after Adjuvant Concomitant Treatment with Radiotherapy and Trastuzumab in Patients with Breast Cancer.

BACKGROUND: The purpose of the study was to find out whether there is a difference in the early parameters of cardiotoxicity (left ventricular ejection fraction [LVEF] and N-terminal pro-B-type natriuretic peptide [NT-proBNP]) between the two groups of patients: the patients treated for left breast cancer (left breast cancer group) and those treated for the right breast cancer (right breast cancer group), after the treatment had been completed. PATIENTS AND METHODS: The study included 175 consecutive patients with human epidermal growth factor receptor-2 (HER2) positive early breast cancer, treated concurrently with trastuzumab and radiotherapy (RT), between June 2005 and December 2010. Echocardiography with LVEF measurement was performed before adjuvant RT (LVEF0) and after the completed treatment (LVEF1,). After the treatment NT-proBNP measurement was done as well. The difference (Δ) between LVEF0 and LVEF1 was analysed (Δ LVEF = LVEF0 - LVEF1) and compared between the two groups. RESULTS: There were 84 patients in the left and 91 in the right breast cancer group. Median observation time was 57 (37-71) months. Mean Δ LVEF (%) was -1.786% in the left and -2.607% in the right breast cancer group (p = 0.562, CI: -2.004 to 3.648). Median NT-proBNP were 111.0 ng/l in the left and 90.0 ng/l in the right breast cancer group (p = 0.545). Echocardiography showed that the patients in the left breast cancer group did not have significantly worse systolic and diastolic left ventricular function in comparison with the patients in the right breast cancer group, but, they had higher incidence of pericardial effusion (9 [11%] vs. 1 [1%]) (p = 0.007). CONCLUSIONS: We did not find any significant differences in the early parameters of cardiotoxicity (LVEF, NT-proBNP) between the observed groups. Patients who received left breast/chest wall irradiation had higher incidence of pericardial effusion.

Pulmonary hypertension in patients with advanced heart failure is associated with increased levels of interleukin-6.

CONTEXT: Inflammatory, endothelial and neurohormonal biomarkers are involved in heart failure (HF) and pulmonary hypertension (PH) pathogenesis. OBJECTIVE: To study these biomarkers in PH due to advanced HF. MATERIALS AND METHODS: Thirty adults with HF were included. Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hsCRP), endothelin-1 and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) were measured in peripheral vein and pulmonary artery during right heart catheterisation. RESULTS: IL-6, TNF-α, hsCRP and NT-proBNP correlated with pulmonary pressures independent of ventricular function, HF etiology and vascular bed. IL-6 was independent predictor of systolic pulmonary artery pressure (sPAP). DISCUSSION AND CONCLUSION: Inflammatory biomarkers correlate to PH severity. IL-6 predicts sPAP in advanced HF.

Cardiotoxicity of concomitant radiotherapy and trastuzumab for early breast cancer.

BACKGROUND: Trastuzumab therapy given in combination with one of several chemotherapy regimens is currently considered the standard of care for the treatment of early-stage, human epidermal growth factor receptor-2 (HER2) -positive breast cancer. The treatment with trastuzumab is due to a significant impact on the survival part of the standard adjuvant treatment of patients with HER2-positive breast cancer. Patients treated with postoperative breast or chest wall irradiation receive trastuzumab concomitant with radiotherapy. In a small proportion of patients trastuzumab causes cardiotoxicity. Preclinical findings indicate a radiosensibilizing effect of trastuzumab in breast cancer cells, but it is not yet clear whether it radiosensibilizes cells of healthy tissues too. CONCLUSIONS: Special attention is required when left breast or left thoracic wall is irradiated in patient receiving trastuzumab, because long-term effects of the concurrent treatment with trastuzumab and radiotherapy are not yet known. In an era where more patients are surviving a diagnosis of breast cancer, better understanding and earlier detection of therapy-induced cardiac toxicity will be of paramount importance.

One-minute sit-to-stand test in patients with pulmonary arterial hypertension associated with congenital heart disease: A single-center prospective study.

BACKGROUND: Patients with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) have reduced exercise capacity. Recently, the 1-minute sit-to-stand test (1MSTST), which measures the number of repetitions from sitting to standing position in 1 minute, has been proposed as an alternative test to the 6-minute walking test (6MWT). The aim of our study was to assess the safety and results of the 1MSTST in comparison to the 6MWT in patients with PAH-CHD. METHODS: Consecutive adult patients with PAH-CHD underwent the 6MWT and the 1MSTST on the same day. The 6-minute walking distance in meters and the number of repetitions on the 1MSTST were measured. Heart rate, peripheral oxygen saturations, Borg dyspnea score, and lower limb fatigue were recorded before and immediately after testing. Correlations between both tests and clinical, laboratory, and imaging parameters were statistically analyzed. RESULTS: The study included 40 patients (50% female, mean age 43 ± 15 years), of whom 29 (72%) had Eisenmenger syndrome and 14 (35%) had Down syndrome. The number of 1MSTST repetitions correlated significantly with 6MWT distance (r = 0.807, p = 0.000). There were no adverse events, and the 1MSTST results correlated with the WHO functional class. Heart rate increase and oxygen desaturation after both tests correlated significantly, but less desaturation was observed after 1MSTST. CONCLUSIONS: Our study showed that the 1MSTST is a safe and easily applicable test in adult patients with PAH-CHD, including patients with Down syndrome. The results of the 1MSTST correlate significantly with the 6MWT, providing an alternative tool for exercise capacity assessment in patients with PAH-CHD.

The association between myocardial ischemia and myocardial dysfunction in adult patients with systemic right ventricle - A single centre multimodality study.

BACKGROUND: The exact interaction of factors leading to myocardial dysfunction and fibrosis of the systemic right ventricle (SRV) is not completely understood. Myocardial ischemia and injury associated with a supply-demand mismatch of the pressure overloaded SRV are thought to play an important role, however studies confirming this are lacking. METHODS: Adult SRV patients were included in this single centre cohort study. All patients underwent a comprehensive diagnostic and imaging workup. A two-day stress-rest SPECT was performed to assess myocardial perfusion. SRV ischemia was defined as decreased segmental tracer uptake during exercise with significant improvement at rest. Contrast enhanced cardiac magnetic resonance imaging (CMR) was also performed in a subgroup of patients without contraindication, to assess focal myocardial fibrosis. Differences between patients with and without SRV ischemia were assessed. RESULTS: Twenty-three SRV patients (15 with transposition of the great arteries after atrial switch procedure and 8 with congenitally corrected transposition of the great arteries; 5 (22%) females; mean age 38 ± 11 years) were included. Seven (30%) patients had SRV ischemia on SPECT. Late gadolinium enhancement on CMR was more common in patients with SRV ischemia (p = 0.002). However, there was no association between SRV ischemia and different echocardiographic or CMR parameters of SRV systolic function, laboratory markers (high-sensitivity troponin I and NT-proBNP) and exercise capacity. CONCLUSIONS: Our multimodality study showed that SRV ischemia in adult SRV patients was associated with more focal myocardial fibrosis, but not with functional or imaging markers of SRV function.

Radiotherapy-Induced Cardiotoxicity: The Role of Multimodality Cardiovascular Imaging.

Radiotherapy (RT) is one of the pillars of cancer therapy. High-dose radiation exposure on the thorax is mainly used in the context of adjuvant RT after breast surgery, in lung and esophageal cancer, and as a complement to systemic treatment in lymphoma. Due to the anatomical proximity, the heart inevitably receives some radiation that can result in acute and chronic cardiotoxicity, leading to heart failure, coronary artery disease, pericardial and valvular heart disease. Current evidence suggests there is no safe radiation dose to the heart, which poses a need for early recognition of RT-induced cardiac injury to initiate cardioprotective treatment and prevent further damage. Multimodality cardiac imaging provides a powerful tool to screen for structural and functional abnormalities secondary to RT. Left ventricular ejection fraction, preferably with three-dimensional echocardiography or cardiovascular magnetic resonance (CMR), and global longitudinal strain with speckle-tracking echocardiography are currently the key parameters to detect cardiotoxicity. However, several novel imaging parameters are tested in the ongoing clinical trials. CMR parametric imaging holds much promise as T1, T2 mapping and extracellular volume quantification allow us to monitor edema, inflammation and fibrosis, which are fundamental processes in RT-induced cardiotoxicity. Moreover, the association between serum biomarkers, genetic polymorphisms and the risk of developing cardiovascular disease after chest RT has been demonstrated, providing a platform for an integrative screening approach for cardiotoxicity. The present review summarizes contemporary evidence of RT-induced cardiac injury obtained from multimodality imaging-echocardiography, cardiovascular computed tomography, CMR and nuclear cardiology. Moreover, it identifies gaps in our current knowledge and highlights future perspectives to screen for RT-induced cardiotoxicity.