Cardiac wasting in head and neck cancer and in cardiac autopsies from different cancer types: A study in a chemo-naïve setting.

BACKGROUND: Cardiac wasting is a detrimental consequence of cancer that has been traditionally ignored and often misinterpreted as an iatrogenic effect. METHODS: We conducted a retrospective study on 42 chemo-naive patients affected by locally advanced head and neck cancer (HNC). Based on unintentional weight loss, patients were divided into cachectic and non-cachectic. Left ventricular mass (LVM), LV wall thickness (LVWT), interventricular septal (IVS) thickness, left ventricular internal diameter diastolic (LVIDd), left ventricular internal diameter systolic (LVIDs), internal ventricular septum diastolic (IVSd), left ventricular posterior wall thickness diastolic (LVPWd) and LV ejection fraction (LVEF) were analysed by echocardiography. In parallel, we retrospectively analysed 28 cardiac autoptic specimens of patients who either died of cancer before chemotherapy or with a diagnosis of cancer at autopsy. Presence or absence of myocardial fibrosis at microscopic observation was used for sample stratification. Conventional histology was performed. RESULTS: Cachectic and non-cachectic patients had a significantly different value of LVWT and IVS thickness and LVPWd. LVWT was 9.08 ± 1.57 versus 10.35 ± 1.41 mm (P = 0.011) in cachectic and non-cachectic patients, IVS was 10.00 mm (8.50-11.00) versus 11.00 mm (10.00-12.00) (P = 0.035), and LVPWd was 9.0 (8.5-10.0) and 10.00 mm (9.5-11.0) (P = 0.019) in cachectic and non-cachectic patients. LVM adjusted for body surface area or height squared did not differ between the two populations. Similarly, LVEF did not show any significant decline. At multivariate logistic regression analysis for some independent predictors of weight loss, only LVWT maintained significant difference between cachectic and non-cachectic patients (P = 0.035, OR = 0.240; P = 0.019). The secondary analysis on autoptic specimens showed no significant change in heart weight, whereas LVWT declined from 9.50 (7.25-11.00) to 7.50 mm (6.00-9.00) in cardiac specimens with myocardial fibrosis (P = 0.043). These data were confirmed in multivariate logistic regression analysis (P = 0.041, OR = 0.502). Histopathological analysis confirmed severe atrophy of cardiomyocytes, fibrosis and oedema as compared with controls. CONCLUSIONS: Subtle changes in heart structure and function occur early in HNC patients. These can be detected with routine echocardiography and may help to select appropriate cancer treatment regimens for these patients. Histopathological analysis provided conclusive evidence that atrophy of cardiomyocytes, oedema and fibrosis occur during cancer progression and may precede the onset of overt cardiac pathology. To our knowledge, this is the first clinical study that establishes a direct relationship between tumour progression and cardiac remodelling in HNCs and the first pathological study conducted on human cardiac autopsies from selected chemo-naïve cancer patients.

How progressive cancer endangers the heart: an intriguing and underestimated problem.

Since it came into being as a discipline, cardio-oncology has focused on the prevention and treatment of cardiotoxicity induced by antitumor chemotherapy and radiotherapy. Over time, it has been proved that even more detrimental is the direct effect generated by cancer cells that release pro-cachectic factors in the bloodstream. Secreted molecules target different organs at a distance, including the heart. Inflammatory and neuronal modulators released by the tumor bulk, either as free molecules or through exosomes, contribute to the pathogenesis of cardiac disease. Progressive cancer causes cachexia and severe cardiac muscle wasting accompanied by cardiomyocyte atrophy, tissue fibrosis, and several functional impairments up to heart failure. The molecular mechanisms responsible for such a cardiac muscle wasting have been partially elucidated in animal models, but minimally investigated in humans, although severe cardiac dysfunction exacerbates global cachexia and hampers efficient anti-cancer treatments. This review provides an overview of cancer-induced structural cardiac and functional damage, drawing on both clinical and scientific research. We start by looking at the pathophysiological mechanisms and evolving epidemiology and go on to discuss prevention, diagnosis, and a multimodal policy of intervention aimed at providing overall prognosis and global care for patients. Despite much interest in the cardiotoxicity of cancer therapies, the direct tumor effect on the heart remains poorly explored. There is still a lack of diagnostic criteria for the identification of the early stages of cardiac disease in cancer patients, while the possibilities that there are for effective prevention are largely underestimated. Research on innovative therapies has claimed considerable advances in preclinical studies, but none of the molecular targets suitable for clinical application has been approved for therapy. These issues are critically discussed here.

Unusual cardiac metastasis of uterine leiomyosarcoma: case report and literature review.

BACKGROUND: Uterine leiomyosarcoma (LMS) is a rare malignancy of mesenchymal tissues and in advanced stages its prognosis is very poor. Surgery followed by radiotherapy and/or chemotherapy is the treatment of choice for advanced disease. Cardiac metastases are very uncommon and only a few cases have been described to date. CASE: A 55-year-old woman was referred to our center for a uterine LMS with lung metastases at diagnosis. After 3 lines of chemotherapy for persistent lung disease, CT scan showed suspected thrombosis in the right pulmonary vein, along with disease progression in the lungs. The patient started treatment with low-molecular-weight heparin and a fourth line of chemotherapy. After 3 months of therapy, a new CT scan showed a larger thrombus and she underwent a cardiology visit that revealed an intracardiac mass. Submitting the patient to palliative surgery or radiation therapy was not possible because of the aggressiveness of the lung metastases, so she continued chemotherapy, resulting in disease stabilization. CONCLUSIONS: Surgery is the best option for intracardiac dissemination of uterine LMS, but when this is not possible based on the performance status of the patient and spread of the disease, the combination of chemotherapy and radiotherapy seems to be the best option according to the literature. In our case we treated the patient only with chemotherapy.

[Right ventricular mural endocarditis: description of a case]. / Endocardite murale del ventricolo destro: descrizione di un caso.

We report the case of a 45-year-old man addicted to intravenous drug abuse who was admitted to our hospital for dyspnea, fever and chest pain. Chest X-ray showed diffuse right lung opacity and pleural effusion. Transthoracic echocardiography and contrast-enhanced cardiac magnetic resonance imaging revealed a plurilobated, highly mobile mass in the right ventricle originating from the moderator band near the apical trabeculae. Cardiac structure and valves were normal. Blood cultures were positive for Staphylococcus hominis. The diagnosis of infective endocarditis with mural vegetation was made. Specific antibiotic therapy was started with success and after 3 weeks the mass disappeared. Infective endocarditis with mural vegetation in the absence of valvular lesions is uncommon. Differential diagnosis is always required, but clinical course should be our guide in decision making.

Electrocardiographic findings and myocardial damage in acute myocarditis detected by cardiac magnetic resonance.

Delayed-contrast-enhancement (DCE) magnetic resonance imaging (MRI) can identify areas of myocardial damage in patients with acute myocarditis (AM). The aim of this study was to assess the electrocardiographic findings in AM diagnosed by DCE-MRI. Eighty-one patients (72 men, 35 ± 13 years) with AM were prospectively enrolled. All of them underwent MRI and 12-lead-ECG recordings. In the admission electrocardiogram (ECG 1), as well as in that obtained 48 h later (ECG 2), the following parameters were analyzed: rhythm, PR, QRS, and QTc-intervals, intraventricular conduction, abnormal Q waves, ST segment elevation, and T wave inversion. On admission, 77 patients (95%) were in sinus rhythm, while four patients (6%) manifested severe arrhythmias. No difference between ECG 1 and ECG 2 was observed regarding abnormal Q waves, PR, QRS, and QTc-intervals. Electrocardiogram 1 was normal in 26 patients (32%, normal ECG group), and abnormal in 55 patients (68%, abnormal ECG group). ST elevation was found in 46 patients (57%), inverted T wave in seven patients (9%) and left bundle branch block (LBBB) in two patients (3%). Areas of DCE suggesting AM were found in each patient. No relationship concerning the location of the involved region (s) was found between ECG (leads with ST/T abnormalities) and MRI (areas showing DCE). The ECG in AM can either be normal or reflect abnormalities including arrhythmias, LBBB, ST segment elevation, and T wave inversion. The location of myocardial involvement deduced on the basis of ECG leads showing ST/T changes is not in close relationship with the areas of ventricular damage detected by MRI.

Metastatic tumor of the heart: description of a case.

We present the case of a 67-year-old man with a carcinoma of the lung and a metastatic tumor of the heart. The diagnosis was made on the basis of echocardiogram. In this patient, the first and unique cardiac symptom was irreversible sustained ventricular arrhythmia leading to death.

Different cardiovascular potential of adult- and fetal-type mesenchymal stem cells in a rat model of heart cryoinjury.

Efficacy of adult (bone marrow, BM) versus fetal (amniotic fluid, AF) mesenchymal stem cells (MSCs) to replenish damaged rat heart tissues with new cardiovascular cells has not yet been established. We investigated on the differentiation potential of these two rat MSC populations in vitro and in a model of acute necrotizing injury (ANI) induced by cryoinjury. Isolated BM-MSCs and AF-MSCs were characterized by flow cytometry and cytocentrifugation and their potential for osteogenic, adipogenic, and cardiovascular differentiation assayed in vitro using specific induction media. The left anterior ventricular wall of syngeneic Fisher 344 (n = 48) and athymic nude (rNu) rats (n = 6) was subjected to a limited, nontransmural epicardial ANI in the approximately one third of wall thickness without significant hemodynamic effects. The time window for in situ stem cell transplantation was established at day 7 postinjury. Fluorochrome (CMTMR)-labeled BM-MSCs (2 x 10(6)) or AF-MSCs (2 x 10(6)) were injected in syngeneic animals (n = 26) around the myocardial lesion via echocardiographic guidance. Reliability of CMTMR cell tracking in this context was ascertained by transplanting genetically labeled BM-MSCs or AF-MSCs, expressing the green fluorescent protein (GFP), in rNu rats with ANI. Comparison between the two methods of cell tracking 30 days after cell transplantation gave slightly different values (1420,58 +/- 129,65 cells/mm2 for CMTMR labeling and 1613.18 +/- 643.84 cells/mm2 for genetic labeling; p = NS). One day after transplantation about one half CMTMR-labeled AF-MSCs engrafted to the injured heart (778.61 +/- 156.28 cells/mm2) in comparison with BM-MSCs (1434.50 +/- 173.80 cells/mm2, p < 0.01). Conversely, 30 days after cell transplantation survived MSCs were similar: 1275.26 +/- 74.51/mm2 (AF-MSCs) versus 1420.58 +/- 129.65/mm2 for BM-MSCs (p = NS). Apparent survival gain of AF-MSCs between the two time periods was motivated by the cell proliferation rate calculated at day 30, which was lower for BM-MSCs (6.79 +/- 0.48) than AF-MSCs (10.83 +/- 3.50; p < 0.01), in the face of a similar apoptotic index (4.68 +/- 0.20 for BM-MSCs and 4.16 +/- 0.58 for AF-MSCs; p = NS). These cells were also studied for their expression of markers specific for endothelial cells (ECs), smooth muscle cells (SMCs), and cardiomyocytes (CMs) using von Willebrand factor (vWf), smooth muscle (SM) alpha-actin, and cardiac troponin T, respectively. Grafted BM-MSCs or AF-MSCs were found as single cell/small cell clusters or incorporated in the wall of microvessels. A larger number of ECs (227.27 +/- 18.91 vs. 150.36 +/- 24.08 cells/mm2, p < 0.01) and CMs (417.91 +/- 100.95 vs. 237.43 +/- 79.99 cells/mm2, p < 0.01) originated from AF-MSCs than from BM-MSCs. Almost no SMCs were seen with AF-MSCs, in comparison to BM-MSCs (98.03 +/- 40.84 cells/mm2), in concordance with lacking of arterioles, which, instead, were well expressed with BM-MSCs (71.30 +/- 55.66 blood vessels/mm2). The number of structurally organized capillaries was slightly different with the two MSCs (122.49 +/- 17.37/mm2 for AF-MSCs vs. 148.69 +/- 54.41/mm2 for BM-MSCs; p = NS). Collectively, these results suggest that, in the presence of the same postinjury microenvironment, the two MSC populations from different sources are able to activate distinct differentiation programs that potentially can bring about a myocardial-capillary or myocardial-capillary-arteriole reconstitution.