Cancer therapy related cardiac dysfunction as a result of Panitumumab.

Panitumumab is a human immunoglobulin monoclonal antibody designed to target the epidermal growth factor receptor (EGFR) which is used in the treatment of metastatic colorectal cancer alone or in combination with chemotherapy. In this report, we present a case of new onset heart failure with reduced ejection fraction in a patient following panitumumab therapy. A 73-year-old gentleman with metastatic rectal adenocarcinoma presented to his local hospital with increased shortness of breath, two months after his first and only dose of panitumumab. A transthoracic echocardiogram demonstrated dilated left ventricle with global hypokinesis and an estimated left ventricular ejection fraction of 25%. Our patient underwent a comprehensive diagnostic assessment at his presentation, including ECG, transthoracic echocardiogram, cardiac magnetic resonance, computed tomography coronary angiography (CTCA), invasive coronary angiogram and 18F-FDG PET-CT. These investigations revealed no evidence of ischemic events or inflammatory processes that could account for the severe left ventricular dysfunction. To our knowledge, this is the first reported case of heart failure with reduced ejection fraction linked to panitumumab with subsequent deep phenotyping. The current guidelines do not recommend specific cardiovascular monitoring protocols for patients receiving anti-EGFR monoclonal antibodies. Until more data are available, it would be prudent to implement the same cardiovascular surveillance measures outlined for individuals receiving osimertinib, which is an EGFR tyrosine kinase inhibitor.

Late cardiotoxicity related to HER2-targeted cancer therapy.

Long-term anti-HER2 therapy in metastatic HER2 + cancers is increasing, but data about the incidence and risk factors for developing late Cancer therapy-related cardiac dysfunction (CTRCD) are missing. We conducted a single-centre, retrospective analysis of a cohort of late anti-HER2 related cardiac dysfunction referred to our Cardio-Oncology service. We include seventeen patients with metastatic disease who developed CTRCD after at least five years of continuous anti-HER2 therapy. Events occurred after a median time of 6.5 years (IQR 5.3-9.0) on anti-HER2 therapy. The lowest (median) LVEF and GLS were 49% (IQR 45-55) and - 15.4% (IQR - 14.9 - -16.3) respectively. All our patients continued or restarted, after a brief interruption, their anti-HER2 therapy. Most (16/17) were started on heart failure medical therapy and normalized their left ventricular ejection fraction at a follow-up. Our study has demonstrated that CTRCD can occur after many years of stability on anti-HER2 therapy and reinforces the importance of continuing cardiovascular surveillance in this population.

Echocardiography versus Cardiac MRI for Measurement of Left Ventricular Ejection Fraction in Individuals with Cancer and Suspected Cardiotoxicity.

Purpose To compare left ventricular ejection fraction (LVEF) measured with echocardiography and cardiac MRI in individuals with cancer and suspected cardiotoxicity and assess the potential effect on downstream clinical decision-making. Materials and Methods In this prospective, single-center observational cohort study, participants underwent same-day two-dimensional (2D) echocardiography and cardiac MRI between 2011 and 2021. Participants with suboptimal image quality were excluded. A subset of 74 participants also underwent three-dimensional (3D) echocardiography. The agreement of LVEF derived from each modality was assessed using Bland-Altman analysis and at relevant thresholds for cardiotoxicity. Results A total of 745 participants (mean age, 60 years ± 5 [SD]; 460 [61.7%] female participants) underwent same-day echocardiography and cardiac MRI. According to Bland-Altman analysis, the mean bias was -3.7% ± 7.6 (95% limits of agreement [LOA]: -18.5% to 11.1%) for 2D echocardiography versus cardiac MRI. In 74 participants who underwent cardiac MRI, 3D echocardiography, and 2D echocardiography, the mean LVEFs were 60.0% ± 10.4, 58.4% ± 9.4, and 57.2% ± 8.9, respectively (P < .001). At the 50% LVEF threshold for detection of cardiotoxicity, there was disagreement for 9.3% of participants with 2D echocardiography and cardiac MRI. Agreement was better with 3D echocardiography and cardiac MRI (mean bias, -1.6% ± 6.3 [95% LOA: -13.9% to 10.7%]) compared with 2D echocardiography and cardiac MRI (mean bias, -2.8% ± 6.3 [95% LOA: -15.2% to 9.6%]; P = .016). Conclusion Two-dimensional echocardiography had variations of ±15% for LVEF measurement compared with cardiac MRI in participants with cancer and led to misclassification of approximately 10% of participants for cardiotoxicity detection. Three-dimensional echocardiography had better agreement with cardiac MRI and should be used as first-line imaging. Keywords: Echocardiography, MR Functional Imaging, Cardiac Supplemental material is available for this article. © RSNA, 2024.

Clinical Utility and Prognostic Value of Coronary Computed Tomography Angiography in Patients With Cancer.

There is growing interest in the role of coronary computed tomography angiography (CTA) in cardio-oncology. However, there is a paucity of real-world experience and outcome data for patients with cancer. This study sought to determine the clinical utility and prognostic value of coronary CTA in patients with cancer. In this prospective, single-center study, we recruited patients with cancer who underwent coronary CTA. Coronary artery disease (CAD) extent was classified as normal, nonobstructive (1% to 49% stenosis), and potentially obstructive (≥50% stenosis). Patients were followed up for a median of 9 months (interquartile range 3 to 30 months) for cancer-related deaths and major adverse cardiovascular events (MACEs) defined as nonfatal myocardial infarction, urgent unplanned revascularization, or cardiovascular death. The mean age of patients (n = 113) was 61 ± 12 years, and 68 were female (60%). The most common underlying cancers were breast (29%) and lymphoma (13%). A total of 25 patients had potentially obstructive CAD, most commonly of the left anterior descending artery. After coronary CTA, 88% statin-naive patients with potentially obstructive CAD were initiated on statin therapy. A total of 28/32 patients who were taking fluoropyrimidine chemotherapy (5-fluorouracil or capecitabine) continued therapy, of whom none had MACEs. Overall, there were no episodes of MACEs in this cohort and 11% had cancer-related deaths. Coronary CTA has an important role in the clinical decision-making in patients with cancer to detect CAD, initiate primary preventative therapy, and guide coronary revascularization. No MACEs occurred. Using this coronary CTA-guided approach, preventative therapy was initiated, and most patients continued prognostically important cancer therapy.

[99mTc]-labelled anti-Programmed Death-Ligand 1 single-domain antibody SPECT/CT: a novel imaging biomarker for myocardial PD-L1 expression.

BACKGROUND: Myocardial programmed death-ligand 1 (PD-L1) expression is implicated in immune checkpoint inhibitor (ICI)-associated myocarditis. Measurement of myocardial PD-L1 expression may have potential use as a mechanistic and predictive biomarker. The aim of this study was to determine non-invasive assessment of myocardial PD-L1 expression using [99mTc]-labelled anti-PD-L1 single-domain antibody (NM-01) SPECT/CT. METHODS: Thoracic [99mTc]NM-01 SPECT/CT was performed in lung cancer patients (n = 10) at baseline and 9-weeks following anti-programmed cell death protein 1 (PD-1) therapy. Baseline and 9-week left ventricular and right ventricular to blood pool ratios (LVmax:BP) and (RVmax:BP) were measured. LVmax was compared to background skeletal muscle (musclemax). Intra-rater reliability was determined by intraclass correlation coefficient (ICC) and Bland-Altman analysis. RESULTS: Mean LVmax:BP values were 2.76 ± 0.67 at baseline vs 2.55 ± 0.77 at 9 weeks (p = 0.42). Mean RVmax:BP was 1.82 ± 0.32 at baseline vs 1.76 ± 0.45 at 9 weeks (p = 0.67). Myocardial PD-L1 expression was at least threefold greater than skeletal muscle at baseline for the LV (LVmax to musclemax 3.71 ± 0.77 vs 0.98 ± 0.20 (p < 0.001)) and at least twofold for the RV (LVmax to musclemax 2.49 ± 0.63 vs 0.98 ± 0.20 (p < 0.001)). There was excellent intra-rater reliability for LVmax:BP with ICC 0.99 (95% confidence interval 0.94-0.99, p < 0.001), mean bias -0.05 ± 0.14 (95% limits of agreement -0.32 to 0.21). There were no major adverse cardiovascular events or myocarditis during follow-up. CONCLUSION: This study is the first to report PD-L1 expression of the heart that can be quantified non-invasively without invasive myocardial biopsy, with high reliability and specificity. This technique can be applied to investigate myocardial PD-L1 expression in ICI-associated myocarditis and cardiomyopathies. Clinical trial registration PD-L1 Expression in Cancer (PECan) study (NCT04436406). https://clinicaltrials.gov/ct2/show/NCT04436406 June 18th, 2020.

Impact of Temporal Resolution and Methods for Correction on Cardiac Magnetic Resonance Perfusion Quantification.

BACKGROUND: Acquisition of magnetic resonance first-pass perfusion images is synchronized to the patient's heart rate (HR) and governs the temporal resolution. This is inherently linked to the process of myocardial blood flow (MBF) quantification and impacts MBF accuracy but to an unclear extent. PURPOSE: To assess the impact of temporal resolution on quantitative perfusion and compare approaches for accounting for its variability. STUDY TYPE: Prospective phantom and retrospective clinical study. POPULATION AND PHANTOM: Simulations, a cardiac perfusion phantom, and 30 patients with (16, 53%) or without (14, 47%) coronary artery disease. FIELD STRENGTH/SEQUENCE: 3.0 T/2D saturation recovery spoiled gradient echo sequence. ASSESSMENT: Dynamic perfusion data were simulated for a range of reference MBF (1 mL/g/min-5 mL/g/min) and HR (30 bpm-150 bpm). Perfusion imaging was performed in patients and a phantom for different temporal resolutions. MBF and myocardial perfusion reserve (MPR) were quantified without correction for temporal resolution or following correction by either MBF scaling based on the sampling interval or data interpolation prior to quantification. Simulated data were quantified using Fermi deconvolution, truncated singular value decomposition, and one-compartment modeling, whereas phantom and clinical data were quantified using Fermi deconvolution alone. STATISTICAL TESTS: Shapiro-Wilk tests for normality, percentage error (PE) for measuring MBF accuracy in simulations, and one-way repeated measures analysis of variance with Bonferroni correction to compare clinical MBF and MPR. Statistical significance set at P < 0.05. RESULTS: For Fermi deconvolution and an example simulated 1 mL/g/min, the MBF PE without correction for temporal resolution was between 55.4% and -62.7% across 30-150 bpm. PE was between -22.2% and -6.8% following MBF scaling and between -14.2% and -14.2% following data interpolation across the same HR. An interpolated HR of 240 bpm reduced PE to ≤10%. Clinical rest and stress MBF and MPR were significantly different between analyses. DATA CONCLUSION: Accurate perfusion quantification needs to account for the variability of temporal resolution, with data interpolation prior to quantification reducing MBF variability across different resolutions. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 1.

Simultaneous 13N-Ammonia and gadolinium first-pass myocardial perfusion with quantitative hybrid PET-MR imaging: a phantom and clinical feasibility study.

BACKGROUND: Positron emission tomography (PET) is the non-invasive reference standard for myocardial blood flow (MBF) quantification. Hybrid PET-MR allows simultaneous PET and cardiac magnetic resonance (CMR) acquisition under identical experimental and physiological conditions. This study aimed to determine feasibility of simultaneous 13N-Ammonia PET and dynamic contrast-enhanced CMR MBF quantification in phantoms and healthy volunteers. METHODS: Images were acquired using a 3T hybrid PET-MR scanner. Phantom study: MBF was simulated at different physiological perfusion rates and a protocol for simultaneous PET-MR perfusion imaging was developed. Volunteer study: five healthy volunteers underwent adenosine stress. 13N-Ammonia and gadolinium were administered simultaneously. PET list mode data was reconstructed using ordered subset expectation maximisation. CMR MBF was quantified using Fermi function-constrained deconvolution of arterial input function and myocardial signal. PET MBF was obtained using a one-tissue compartment model and image-derived input function. RESULTS: Phantom study: PET and CMR MBF measurements demonstrated high repeatability with intraclass coefficients 0.98 and 0.99, respectively. There was high correlation between PET and CMR MBF (r = 0.98, p < 0.001) and good agreement (bias - 0.85 mL/g/min; 95% limits of agreement 0.29 to - 1.98). Volunteer study: Mean global stress MBF for CMR and PET were 2.58 ± 0.11 and 2.60 ± 0.47 mL/g/min respectively. On a per territory basis, there was moderate correlation (r = 0.63, p = 0.03) and agreement (bias - 0.34 mL/g/min; 95% limits of agreement 0.49 to - 1.18). CONCLUSION: Simultaneous MBF quantification using hybrid PET-MR imaging is feasible with high test repeatability and good to moderate agreement between PET and CMR. Future studies in coronary artery disease patients may allow cross-validation of techniques.

Importance of operator training and rest perfusion on the diagnostic accuracy of stress perfusion cardiovascular magnetic resonance.

BACKGROUND: Clinical evaluation of stress perfusion cardiovascular magnetic resonance (CMR) is currently based on visual assessment and has shown high diagnostic accuracy in previous clinical trials, when performed by expert readers or core laboratories. However, these results may not be generalizable to clinical practice, particularly when less experienced readers are concerned. Other factors, such as the level of training, the extent of ischemia, and image quality could affect the diagnostic accuracy. Moreover, the role of rest images has not been clarified. The aim of this study was to assess the diagnostic accuracy of visual assessment for operators with different levels of training and the additional value of rest perfusion imaging, and to compare visual assessment and automated quantitative analysis in the assessment of coronary artery disease (CAD). METHODS: We evaluated 53 patients with known or suspected CAD referred for stress-perfusion CMR. Nine operators (equally divided in 3 levels of competency) blindly reviewed each case twice with a 2-week interval, in a randomised order, with and without rest images. Semi-automated Fermi deconvolution was used for quantitative analysis and estimation of myocardial perfusion reserve as the ratio of stress to rest perfusion estimates. RESULTS: Level-3 operators correctly identified significant CAD in 83.6% of the cases. This percentage dropped to 65.7% for Level-2 operators and to 55.7% for Level-1 operators (p < 0.001). Quantitative analysis correctly identified CAD in 86.3% of the cases and was non-inferior to expert readers (p = 0.56). When rest images were available, a significantly higher level of confidence was reported (p = 0.022), but no significant differences in diagnostic accuracy were measured (p = 0.34). CONCLUSIONS: Our study demonstrates that the level of training is the main determinant of the diagnostic accuracy in the identification of CAD. Level-3 operators performed at levels comparable with the results from clinical trials. Rest images did not significantly improve diagnostic accuracy, but contributed to higher confidence in the results. Automated quantitative analysis performed similarly to level-3 operators. This is of increasing relevance as recent technical advances in image reconstruction and analysis techniques are likely to permit the clinical translation of robust and fully automated quantitative analysis into routine clinical practice.

Feasibility of simultaneous PET-MR perfusion using a novel cardiac perfusion phantom.

BACKGROUND: PET-MR scanners are beginning to be employed for quantitative myocardial perfusion imaging. In order to examine simultaneous perfusion calculations, this work describes a feasibility study of simultaneous PET-MR of gadolinium-based contrast agent (GBCA) and PET radiotracer in a novel cardiac perfusion phantom. RESULTS: [18F]F- and GBCA were injected simultaneously into a cardiac phantom using a range of ground-truth myocardial perfusion rates of 1 to 5 ml/g/min. PET quantification of K1 (ml/g/min) was performed using a single tissue compartment model. MR perfusion was calculated using a model-independent signal deconvolution technique. PET and MR signal traces from the phantom aorta and myocardial sections show true simultaneous PET and MR arterial input functions (AIF) and myocardial uptake respectively at each perfusion rate. Calculation of perfusion parameters showed both K1 and h(t = 0) (PET and MR perfusion parameters respectively) to be linearly related with the ground truth perfusion rate (PT ), and also linearly related to each other (R2 = 0.99). The highest difference in perfusion values between K1 and PT was 16% at 1 ml/g/min, and the mean difference for all other perfusion rates was <3%. CONCLUSIONS: The perfusion phantom allows accurate and reproducible simulation of the myocardial kinetics for simultaneous PET-MR imaging, and may find use in protocol design and development of PET-MR based quantification techniques and direct comparison of quantification of the two modalities.

Local anaesthetic drugs: adverse effects as reported through the ADROIT system in the UK.

PURPOSE: Adverse drug reactions (ADRs) to local anaesthetic drugs are reported voluntarily through the Adverse Drug Reporting On Line Tracking system (ADROIT). We aimed to determine hazards associated with drugs commonly used in anaesthesia including ropivacaine and levobupivacaine. METHODS: The ADROIT database was queried for all ADRs to local anaesthetics used in anaesthesia and surgery between 1967 and 2005. Details of age, sex, suspect drug, date and reaction details were analysed. RESULTS: There were 985 reports analysed, 797 for lidocaine, 160 for bupivacaine, 16 for ropivacaine and 12 for levobupivacaine. The female to male ratio was 1.6:1 and age was not a factor determining the frequency of reactions. A vasoconstrictor was included in the lidocaine formulation in 27% of reports. When methylprednisolone (Depo-Medrone) or prilocaine (as EMLA cream) were used in combination with lidocaine, the frequency of allergic reports increased significantly (p < 0.0001). Levobupivacaine demonstrated a hazard signal for cardiovascular symptoms. Fatality rate within the reports was higher for bupivacaine (11%) than for lidocaine (3%). CONCLUSIONS: The patient's age and sex were not found to influence the type of reactions reported. Lidocaine with methylprednisolone or prilocaine (as EMLA(TM) cream) generated the largest number of reports of allergic phenomena. Fatalities were most frequently reported in association with bupivacaine.