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.

Prediction of contrast induced acute kidney injury using novel biomarkers following contrast coronary angiography.

BACKGROUND/INTRODUCTION: Chronic kidney disease (CKD) is a risk factor for contrast induced acute kidney injury (CI-AKI). Contrast angiography in CKD patients is a common procedure. Creatinine is a delayed marker of CI-AKI and delays diagnosis which results in significant morbidity and mortality. AIM: Early diagnosis of CI-AKI requires validated novel biomarkers. DESIGN: A prospective observation study of 301 consecutive CKD patients undergoing coronary angiography was performed. METHODS: Samples for plasma neutrophil gelatinase-associated lipocalin (NGAL), serum liver fatty acid-binding protein (L-FABP), serum kidney injury marker 1, serum interleukin 18 and serum creatinine were taken at 0, 1, 2, 4, 6 and 48 h post-contrast. Urinary NGAL and urinary cystatin C were collected at 0, 6 and 48 h. Incidence of major adverse clinical events (MACE) was recorded at 1 year. CI-AKI was defined as an absolute delta rise in creatinine of ≥26.5 µmol/l or a 50% relative rise from baseline at 48 h following contrast. RESULTS: CI-AKI occurred in 28 (9.3%) patients. Plasma NGAL was most predictive of CI-AKI at 6 h. L-FABP performed best at 4 h. A combination of Mehran score > 10, 4 h L-FABP and 6 h NGAL improved specificity to 96.7%. MACE was statistically higher at 1 year in CI-AKI patients (25.0 vs. 6.2% in non-CI-AKI patients). DISCUSSION/CONCLUSION: Mehran risk score, 4 h serum L-FAPB and 6 h plasma NGAL performed best at early CI-AKI prediction. CI-AKI patients were four times more likely to develop MACE and had a trebling of mortality risk at 1 year.

Cardiotoxicity Following Cancer Treatment.

More than half of those born after 1960 will develop cancer during their lifetime. Fortunately, owing to improved diagnosis and treatment, cure rates have risen steadily over the last three decades. With an increased survivorship, more will experience adverse effects of cancer therapeutics on the heart. As the oncologist's focus begins to encompass the issues of cancer survivorship, awareness of the management of cardiac toxicity would be prudent for all physicians looking after patients with cancer.

Novel Biomarkers of Acute Kidney Injury After Contrast Coronary Angiography.

Acute kidney injury (AKI), defined as a rise in serum creatinine of greater than 25% from baseline measured at 48 hours after renal insult, may follow iodinated contrast coronary angiography. Termed contrast-induced nephropathy, it can result in considerable morbidity and mortality. Measurement of serum creatinine as a functional biomarker of glomerular filtration rate is widely used for detection of AKI, but it lacks sensitivity for the early diagnosis of AKI (typically rising 24 hours after functional loss) and, as a solely functional marker of glomerular filtration rate, is unable to differentiate among the various causes of AKI. These intrinsic limitations to creatinine measurement and the recognition that improved clinical outcomes are linked to a more timely diagnosis of AKI, has led investigators to search for novel biomarkers of "early" kidney injury. Several studies have investigated the utility of renal injury biomarkers in a variety of clinical settings including angiography/percutaneous coronary intervention, coronary artery bypass graft surgery, sepsis in intensive care patients, and pediatric cardiac surgery. In this article, we discuss the use of iodinated contrast for coronary procedures and the risk factors for contrast-induced nephropathy, followed by a review the potential diagnostic utility of several novel biomarkers of early AKI in the clinical settings of coronary angiography/percutaneous coronary intervention. In particular, we discuss neutrophil gelatinase associated lipocalin in depth. If validated, such biomarkers would facilitate earlier AKI diagnosis and improve clinical outcomes.

Constriction infection.

Chronic constrictive pericarditis (CCP) is a clinical syndrome caused by compression of the heart due to a thickened or rigid pericardium. In the affluent West, the majority of cases of CCP are neither tuberculous nor calcific. In an American cohort undergoing pericardectomy for the condition, only 27% had calcification and under 10% had TB [1]. As a result, pericardial calcification (PC) as a marker of CCP has become neglected. We present a 48-year-old male admitted with atrial flutter, acute chest infection and signs of right heart congestion. PC was documented one year previously on a non-contrast CT chest. On this occasion, cardiac catheterisation confirmed hemodynamically significant CCP and cardiac magnetic resonance (cMR) study showed contiguous mass lesions in the pericardium, compression of the right ventricle, enlargement of the right atrium, hepatic enlargement and a pneumonic process in the left lung. He was commenced on antibiotics and anti-tuberculous therapy with a diagnosis of bacterial super-infection of tuberculous CCP. This was confirmed at pericardectomy along with an infected fistula into the left lung. Any finding of PC should be followed up with a thorough haemodynamic and anatomical assessment using any of a wide range of non-invasive imaging modalities.

Elevated CA 125 and ascites: not always malignancy.

BACKGROUND: We present two clinical cases from a single institution where a final diagnosis of cardiac failure was made following the initial finding of ascites and an elevated CA 125 level. In both cases gynaecological malignancy was initially suspected. METHODS: Following negative confirmatory tests for gynaecological malignancy, echocardiography was undertaken. RESULTS: Patient 1 had severe right ventricular dilatation and dysfunction. Patient 2 had biventricular dysfunction with pulmonary hypertension. Both patients responded to standard therapy for heart failure, including loop diuretics.