Dose-dependent changes in cardiac function, strain and remodelling in a preclinical model of heart base irradiation.

BACKGROUND AND PURPOSE: Radiation induced cardiotoxicity (RICT) is as an important sequela of radiotherapy to the thorax for patients. In this study, we aim to investigate the dose and fractionation response of RICT. We propose global longitudinal strain (GLS) as an early indicator of RICT and investigate myocardial deformation following irradiation. METHODS: RICT was investigated in female C57BL/6J mice in which the base of the heart was irradiated under image-guidance using a small animal radiation research platform (SARRP). Mice were randomly assigned to a treatment group: single-fraction dose of 16 Gy or 20 Gy, 3 consecutive fractions of 8.66 Gy, or sham irradiation; biological effective doses (BED) used were 101.3 Gy, 153.3 Gy and 101.3 Gy respectively. Longitudinal transthoracic echocardiography (TTE) was performed from baseline up to 50 weeks post-irradiation to detect structural and functional effects. RESULTS: Irradiation of the heart base leads to BED-dependent changes in systolic and diastolic function 50 weeks post-irradiation. GLS showed significant decreases in a BED-dependent manner for all irradiated animals, as early as 10 weeks after irradiation. Early changes in GLS indicate late changes in cardiac function. BED-independent increases were observed in the left ventricle (LV) mass and volume and myocardial fibrosis. CONCLUSIONS: Functional features of RICT displayed a BED dependence in this study. GLS showed an early change at 10 weeks post-irradiation. Cardiac remodelling was observed as increases in mass and volume of the LV, further supporting our hypothesis that dose to the base of the heart drives the global heart toxicity.

The Association of Incidental Radiation Dose to the Heart Base with Overall Survival and Cardiac Events after Curative-intent Radiotherapy for Non-small Cell Lung Cancer: Results from the NI-HEART Study.

AIMS: Cardiac disease is a dose-limiting toxicity in non-small cell lung cancer radiotherapy. The dose to the heart base has been associated with poor survival in multiple institutional and clinical trial datasets using unsupervised, voxel-based analysis. Validation has not been undertaken in a cohort with individual patient delineations of the cardiac base or for the endpoint of cardiac events. The purpose of this study was to assess the association of heart base radiation dose with overall survival and the risk of cardiac events with individual heart base contours. MATERIALS AND METHODS: Patients treated between 2015 and 2020 were reviewed for baseline patient, tumour and cardiac details and both cancer and cardiac outcomes as part of the NI-HEART study. Three cardiologists verified cardiac events including atrial fibrillation, heart failure and acute coronary syndrome. Cardiac substructure delineations were completed using a validated deep learning-based autosegmentation tool and a composite cardiac base structure was generated. Cox and Fine-Gray regressions were undertaken for the risk of death and cardiac events. RESULTS: Of 478 eligible patients, most received 55 Gy/20 fractions (96%) without chemotherapy (58%), planned with intensity-modulated radiotherapy (71%). Pre-existing cardiovascular morbidity was common (78% two or more risk factors, 46% one or more established disease). The median follow-up was 21.1 months. Dichotomised at the median, a higher heart base Dmax was associated with poorer survival on Kaplan-Meier analysis (20.2 months versus 28.3 months; hazard ratio 1.40, 95% confidence interval 1.14-1.75, P = 0.0017) and statistical significance was retained in multivariate analyses. Furthermore, heart base Dmax was associated with pooled cardiac events in a multivariate analysis (hazard ratio 1.75, 95% confidence interval 1.03-2.97, P = 0.04). CONCLUSIONS: Heart base Dmax was associated with the rate of death and cardiac events after adjusting for patient, tumour and cardiovascular factors in the NI-HEART study. This validates the findings from previous unsupervised analytical approaches. The heart base could be considered as a potential sub-organ at risk towards reducing radiation cardiotoxicity.

Multidetector-row CT features and histopathological analysis of pericardial recesses in dogs.

At the level of pericardial reflections and near the great thoracic vessels, pericardial recesses (PRs) are present, where fluid can collect to increase the pericardial reserve volume. To date, these structures have not been described in vivo in veterinary patients. The aims of this observational and descriptive study were to describe the location and appearance of PRs in dogs, as seen with multidetector-row CT (MDCT), and to develop a dedicated imaging technique for their best visualization. Dogs who underwent MDCT examination of the whole body were included in the study and CT data were retrospectively evaluated. Dogs with any thoracic abnormality were excluded. MDCT analysis of the PR's was compared with the pathological features of PRs. PRs were identified as fluid-attenuating (10-30 HU), non-enhancing structures showing varied appearance. Two types of PRs were identified at the level of the transverse sinus of the pericardium and classified on the basis of their anatomic location: the aortic recess and the pulmonic recess. A third pericardial fluid-containing structure was seen in a little number of cases, at the level of the termination of the caudal vena cava into the right atrium. A dorsal, slight oblique multiplanar section through the aortic bulb resulted the best technique for visualization of all the recesses. Anatomo-pathological evaluation confirmed the location and the presence of pocket-like reflections of the pericardium identified with 3D-CT models. Knowledge of the CT appearance of the pericardial recesses is necessary in order to avoid their misinterpretation and subsequent unnecessary invasive investigations.

Intracardiac malignant nonchromaffin paraganglioma (chemodectoma) in a cat.

A 5-year-old male castrated Domestic Shorthair cat was presented to a veterinary specialty hospital for evaluation of large-volume pleural effusion. Echocardiography revealed a large intracardiac mass at the level of the interatrial septum impairing right atrial inflow resulting in lymphocytic pleural effusion and ascites. Differential diagnoses included lymphoma, hemangiosarcoma, rhabdomyosarcoma, chemodectoma, neurofibrosarcoma, myxoma, metastatic carcinoma or intracardiac thrombus, abscess or granuloma. Due to poor long-term prognosis and recurrent, large-volume pleural effusion, the cat was humanely euthanized. The heart was submitted for histopathologic evaluation. The mass was subsequently determined to be a malignant extra-adrenal nonchromaffin paraganglioma (chemodectoma) arising from the pulmonary trunk near its bifurcation in the region of the glomus pulmonale. Chemodectomas are rare in cats and to the authors' knowledge, there are no reports of one originating from the glomus pulmonale.

A Pilot Study of Safer Radiation Dosage to the Heart and Its Subregions.

Background and Objectives: The real impact of ionizing radiation on the heart and poorer overall survival for patients with non small cell lung cancer (NSCLC) remains unclear. This study aims to determine the safe dose constraints to the heart's subregions that could prevent patients' early non-cancerous death and improve their quality of life. Methods and Materials: A retrospective cohort study was performed containing 51 consecutive patients diagnosed with stage III NSCLC and treated using 3D, Intensity-modulated radiation therapy (IMRT), and Volumetric modulated arc therapy (VMAT) radiotherapy. For a dosimetric analysis, these structures were chosen: heart, heart base (HB), and region of great blood vessels (GBV). Dose-volume histograms (DVH) were recorded for all mentioned structures. Maximum and mean doses to the heart, HB, the muscle mass of the HB, and GBV were obtained. V10-V60 (%) parameters were calculated from the DVH. After performed statistical analysis, logistic regression models were created, and critical doses calculated. Results: The critical dose for developing a fatal endpoint for HB was 30.5 Gy, while for GBV, it was 46.3 Gy. Increasing the average dose to the HB or GBV by 1 Gy from the critical dose further increases the possibility of early death by 22.0% and 15.8%, respectively. Conclusions: We suggest that the non-canonical sub-regions of the heart (HB and GBV) should be considered during the planning stage. Additional constraints of the heart subregions should be chosen accordingly, and we propose that the mean doses to these regions be 30.5 Gy and 46.3 Gy, respectively, or less. Extrapolated DVH curves for both regions may be used during the planning stage with care.

A Multi-Institutional Retrospective Analysis of Toceranib Phosphate for Presumed or Confirmed Canine Aortic Body Chemodectomas.

Aortic body tumors, specifically chemodectomas, are the second most common type of canine cardiac tumor; however, information about treatment is currently lacking. This study included dogs with a presumptive or definitive diagnosis of an aortic body chemodectoma that underwent treatment with toceranib phosphate. Cases were solicited via the American College of Veterinary Internal Medicine Cardiology, Internal Medicine, and Oncology listservs using an electronic survey. Cox multivariate analysis of factors potentially impacting survival time was completed. Twenty-seven (27) cases were included in analysis. The clinical benefit rate (complete remission, partial remission, or stable disease >10 weeks) was 89%. A median survival time of 478 days was found for those receiving toceranib alone (n = 14), which was not statistically different from those treated with additional modalities (521 days). No factors evaluated statistically impacted outcome. Further, prospective studies are warranted to evaluate the use of toceranib for the treatment of canine aortic body chemodectomas.

Mediastinal histoplasmosis with cardiac involvement in a cat.

Histoplasmosis is the second most common fungal infection reported among domestic felines in the United States. Dissemination of the organism after inoculation is common and affected organ systems include the respiratory tract, gastrointestinal tract, reticuloendothelial organs, skeletal system, integument, and ocular system. However, histoplasmosis presenting as a discrete granulomatous mass identified on echocardiogram has never been reported in the veterinary literature. Here, we describe the first case of feline histoplasmosis presenting as a granuloma with cardiac involvement. The patient, a 6-year-old male neutered domestic longhair feline, was referred for tachypnea and dyspnea. A mass in the cranial mediastinum abutting the heart was diagnosed via two-dimensional echocardiography. Cytology of fine needle aspirates from the mass revealed round yeast structures consistent with Histoplasma spp. The patient was treated with oral fluconazole therapy, and subsequent rechecks have shown marked improvement in clinical parameters, lesion size, and antigen concentrations.

Retrospective evaluation of canine heart base tumours treated with toceranib phosphate (Palladia): 2011-2018.

Heart base tumours (HBT) occur commonly in older, brachycephalic dogs. A presumptive diagnosis is made based on location and appearance of the tumour via echocardiogram. Effective treatment options are limited to surgery (when feasible) or radiation therapy. Benefit of medical management is presently unknown. The goal of this retrospective study was to assess the efficacy and tolerability of toceranib phosphate for dogs with HBT. Twenty-eight dogs with histologically, cytologically confirmed or presumed HBT were evaluated retrospectively. Twenty-seven dogs were treated with single agent toceranib. One dog received combination therapy with concurrent metronomic chemotherapy. This dog was not included in response or survival analysis. Factors assessed included clinical signs, hematologic/biochemical parameters and response to treatment. For the 27 dogs receiving single agent toceranib, an overall response rate of 10% was found. Overall median survival time was 823 days (range, 68-1190 days). The overall response rate for the dogs presenting with metastasis was 28.5%, with a median survival time of 532 days (range, 77-679 days). This was not significantly different than the median survival time of 796 days for dogs who did not present with metastasis. Of the dogs displaying clinical signs at the time of diagnosis, 90% had improvement and 81% had complete resolution of signs after starting toceranib. Toxicity was seen in 54% of dogs with gastrointestinal distress as the most common toxicity but dose reductions were infrequent required. Results demonstrate that toceranib phosphate is a well-tolerated and effective treatment for inoperable canine heart base tumours including dogs with advanced or metastatic disease.

Extracardiac intrapericardial myxosarcoma causing right ventricular outflow tract obstruction in a dog.

A 13-year-old male castrated pomeranian cross was referred for evaluation of episodes of collapse and a suspected cardiac mass. The presence of a mass at the base of the heart within the pericardial space was confirmed by echocardiography. Additional diagnostics included computed tomography, ultrasound-guided fine-needle aspirate, and thoracic radiographs. The mass was surgically debulked and diagnosed as myxosarcoma via histopathology. This case report describes the diagnostic imaging, laboratory findings, and short-term positive clinical outcome of a dog with a myxosarcoma in a previously undescribed location.

Pilot study to determine the feasibility of radiation therapy for dogs with right atrial masses and hemorrhagic pericardial effusion.

OBJECTIVES: To determine the short-term safety and biologic activity of radiation therapy (RT) for presumptive cardiac hemangiosarcoma in pet dogs. ANIMALS: Six dogs with echocardiographic evidence of a right atrial/auricular mass, and hemorrhagic pericardial effusion, were enrolled in a prospective, single-arm clinical trial. METHODS: A single fraction of 12 Gy was delivered using conformal external beam irradiation. Serum cardiac troponin I and plasma concentrations of vascular endothelial growth factor were quantified before, 4 and 24 h after RT. The frequency of required pericardiocenteses (quantified as the number of pericardiocenteses per week) before RT was compared to that after treatment. Overall survival time was determined. RESULTS: No treatment-related complications were observed. Pericardiocentesis was performed an average of 0.91 times per week before RT, and an average of 0.21 times per week after RT; this difference was statistically significant (p=0.03, as compared using a Wilcoxon signed-rank test of paired data). Pre- and post-treatment plasma vascular endothelial growth factor concentrations were not significantly different at any time point; there was a statistically significant (p=0.04; Friedman's test for non-parametric repeated measures) increase in cardiac troponin concentrations 4 h after irradiation. Median overall survival time was 79 days. CONCLUSIONS: In this population of dogs, RT was delivered without complication, and appears to have reduced the frequency of periacardial tamponade that necessitated pericardiocentesis. Serum cardiac troponin levels are altered after RT. RT alone, or in combination with chemotherapy, may provide clinical benefit to dogs with presumptive diagnoses of cardiac hemangiosarcoma.

Prevalência e aspectos anatomopatológicos das neoplasias primárias do coração, de tecidos da base do coração e metastáticas, em cães do Sul de Minas Gerais (1994-2009) / Prevalence and anatomopathological findings of primary cardiac neoplasms of the heart base tissues and metastases in dogs from southern Minas Gerais, Brazil (1994-2009)

Este estudo teve como objetivo determinar a prevalência e achados anatomopatológicos de tumores primários e metastáticos do coração ou de tecidos da base do coração, diagnosticados em caninos do Sul de Minas Gerais. O diagnóstico foi realizado mediante análise histopatológica e imuno-histoquímica das neoplasias. Durante os anos de 1994-2009, foram realizadas 2397 necropsias em caninos. Neoplasias no coração foram detectadas em 31 cães (1,29%), onde, sete (22,58%) eram primárias e 24 (77,42%) metastáticas. As neoplasias diagnosticadas como primárias do coração foram o hemangiossarcoma (1/7) e o mixoma (1/7); e como primárias da base do coração o quimiodectoma (3/7) e o carcinoma de tireoide ectópica (2/7). A frequência foi maior em cães machos (5/7), da raça Boxer (3/7) e com idade média de 9,7±1,88 anos. Nas neoplasias metastáticas, a frequência foi maior em fêmeas (15/24), em cães da raça Rottweiler (7/24) e a idade média foi de 7,5±3,23 anos, sendo o linfoma de células T a neoplasia metastática de maior ocorrência (7/27).

The purpose of this study was to determine the prevalence and anatomopathological findings of primary and metastatic heart tumors and from heart base tumors diagnosed in dogs from southern Minas Gerais, Brazil. The diagnosis was based on histological characteristics and immunophenotyping of the tumors cells. From 1994 to 2009, 2397 necropsies of dogs were performed. Cardiac neoplasms were diagnosed in 31 dogs (1.29%), where seven (22.58%) were primary and 24 (77.42%) were metastatic. Neoplasms of the heart diagnosed as primary were hemangiosarcoma (1/7) and myxoma (1/7), and, primary of heart base, the chemodectoma (3/7) and ectopic thyroid carcinoma (2/7). Frequency was higher in male dogs (5/7), of Boxer breed (3/7) with mean age of 9.7±1.88 years. In metastatic neoplasms, the frequency was higher in female dogs (15/24), of Rottweiler breed (7/24) with the mean age of 7.5±3.23 years. The T cell lymphoma (7/27) was the most frequent neoplasm, diagnosed as metastatic.