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.

Perceptual Learning of Noise-Vocoded Speech Under Divided Attention.

Speech perception performance for degraded speech can improve with practice or exposure. Such perceptual learning is thought to be reliant on attention and theoretical accounts like the predictive coding framework suggest a key role for attention in supporting learning. However, it is unclear whether speech perceptual learning requires undivided attention. We evaluated the role of divided attention in speech perceptual learning in two online experiments (N = 336). Experiment 1 tested the reliance of perceptual learning on undivided attention. Participants completed a speech recognition task where they repeated forty noise-vocoded sentences in a between-group design. Participants performed the speech task alone or concurrently with a domain-general visual task (dual task) at one of three difficulty levels. We observed perceptual learning under divided attention for all four groups, moderated by dual-task difficulty. Listeners in easy and intermediate visual conditions improved as much as the single-task group. Those who completed the most challenging visual task showed faster learning and achieved similar ending performance compared to the single-task group. Experiment 2 tested whether learning relies on domain-specific or domain-general processes. Participants completed a single speech task or performed this task together with a dual task aiming to recruit domain-specific (lexical or phonological), or domain-general (visual) processes. All secondary task conditions produced patterns and amount of learning comparable to the single speech task. Our results demonstrate that the impact of divided attention on perceptual learning is not strictly dependent on domain-general or domain-specific processes and speech perceptual learning persists under divided attention.

Cardiovascular health-related quality of life in cancer: a prospective study comparing the ESC HeartQoL and EORTC QLQ-C30 questionnaire.

AIMS: Health-related quality of life (HRQoL) is highly relevant in cancer and often assessed with the EORTC QLQ-C30. Cardiovascular HRQoL in cancer can be measured with the ESC HeartQoL questionnaire. We compared these instruments and examined their prognostic value. METHODS AND RESULTS: Summary scores for EORTC QLQ-C30 (0-100 points) and ESC HeartQoL (0-3 points) questionnaires were prospectively assessed in 290 patients with mostly advanced cancer (stage 3/4: 81%, 1-year mortality: 36%) and 50 healthy controls (similar age and sex). Additionally, physical function and activity assessments were performed. Both questionnaires demonstrated reduced HRQoL in patients with cancer versus controls (EORTC QLQ-C30: 67 ± 20 vs. 91 ± 11, p < 0.001; ESC HeartQoL: 1.8 ± 0.8 vs. 2.7 ± 0.4, p < 0.001). The instruments were strongly correlated with each other (summary scores [r = 0.76], physical [r = 0.81], and emotional subscales [r = 0.75, all p < 0.001]) and independently associated with all-cause mortality (best cut-offs: EORTC QLQ-C30 <82.69: hazard ratio [HR] 2.33, p = 0.004; ESC HeartQoL <1.50: HR 1.85, p = 0.004 - adjusted for sex, age, left ventricular ejection fraction, N-terminal pro-B-type natriuretic peptide [NT-proBNP], high-sensitivity troponin T, cancer stage/type), with no differences in the strength of the association by sex (p-interaction > 0.9). Combining both questionnaires identified three risk groups with highest mortality in patients below both cut-offs (vs. patients above both cut-offs: HR 3.60, p < 0.001). Patients with results below both cut-offs, showed higher NT-proBNP and reduced physical function and activity. CONCLUSIONS: The EORTC QLQ-C30 and ESC HeartQoL - assessing cancer and cardiovascular HRQoL - are both associated with increased mortality in cancer patients, with even greater stratification by combing both. Reduced HRQoL scores were associated with elevated cardiovascular biomarkers and decreased functional status.

Clinical and Prognostic Relevance of Cardiac Wasting in Patients With Advanced Cancer.

BACKGROUND: Body wasting in patients with cancer can affect the heart. OBJECTIVES: The frequency, extent, and clinical and prognostic importance of cardiac wasting in cancer patients is unknown. METHODS: This study prospectively enrolled 300 patients with mostly advanced, active cancer but without significant cardiovascular disease or infection. These patients were compared with 60 healthy control subjects and 60 patients with chronic heart failure (ejection fraction <40%) of similar age and sex distribution. RESULTS: Cancer patients presented with lower left ventricular (LV) mass than healthy control subjects or heart failure patients (assessed by transthoracic echocardiography: 177 ± 47 g vs 203 ± 64 g vs 300 ± 71 g, respectively; P < 0.001). LV mass was lowest in cancer patients with cachexia (153 ± 42 g; P < 0.001). Importantly, the presence of low LV mass was independent of previous cardiotoxic anticancer therapy. In 90 cancer patients with a second echocardiogram after 122 ± 71 days, LV mass had declined by 9.3% ± 1.4% (P < 0.001). In cancer patients with cardiac wasting during follow-up, stroke volume decreased (P < 0.001) and resting heart rate increased over time (P = 0.001). During follow-up of on average 16 months, 149 patients died (1-year all-cause mortality 43%; 95% CI: 37%-49%). LV mass and LV mass adjusted for height squared were independent prognostic markers (both P < 0.05). Adjustment of LV mass for body surface area masked the observed survival impact. LV mass below the prognostically relevant cutpoints in cancer was associated with reduced overall functional status and lower physical performance. CONCLUSIONS: Low LV mass is associated with poor functional status and increased all-cause mortality in cancer. These findings provide clinical evidence of cardiac wasting-associated cardiomyopathy in cancer.

No evidence for a benefit from masker harmonicity in the perception of speech in noise.

When assessing the intelligibility of speech embedded in background noise, maskers with a harmonic spectral structure have been found to be much less detrimental to performance than noise-based interferers. While spectral "glimpsing" in between the resolved masker harmonics and reduced envelope modulations of harmonic maskers have been shown to contribute, this effect has primarily been attributed to the proposed ability of the auditory system to cancel harmonic maskers from the signal mixture. Here, speech intelligibility in the presence of harmonic and inharmonic maskers with similar spectral glimpsing opportunities and envelope modulation spectra was assessed to test the theory of harmonic cancellation. Speech reception thresholds obtained from normal-hearing listeners revealed no effect of masker harmonicity, neither for maskers with static nor dynamic pitch contours. The results show that harmonicity, or time-domain periodicity, as such, does not aid the segregation of speech and masker. Contrary to what might be assumed, this also implies that the saliency of the masker pitch did not affect auditory grouping. Instead, the current data suggest that the reduced masking effectiveness of harmonic sounds is due to the regular spacing of their spectral components.

Healthcare systems data in the context of clinical trials - A comparison of cardiovascular data from a clinical trial dataset with routinely collected data.

BACKGROUND: Routinely-collected healthcare systems data (HSD) are proposed to improve the efficiency of clinical trials. A comparison was undertaken between cardiovascular (CVS) data from a clinical trial database with two HSD resources. METHODS: Protocol-defined and clinically reviewed CVS events (heart failure (HF), acute coronary syndrome (ACS), thromboembolic stroke, venous and arterial thromboembolism) were identified within the trial data. Data (using pre-specified codes) was obtained from NHS Hospital Episode Statistics (HES) and National Institute for Cardiovascular Outcomes Research (NICOR) HF and myocardial ischaemia audits for trial participants recruited in England between 2010 and 2018 who had provided consent. The primary comparison was trial data versus HES inpatient (APC) main diagnosis (Box-1). Correlations are presented with descriptive statistics and Venn diagrams. Reasons for non-correlation were explored. RESULTS: From 1200 eligible participants, 71 protocol-defined clinically reviewed CVS events were recorded in the trial database. 45 resulted in a hospital admission and therefore could have been recorded by either HES APC/ NICOR. Of these, 27/45 (60%) were recorded by HES inpatient (Box-1) with an additional 30 potential events also identified. HF and ACS were potentially recorded in all 3 datasets; trial data recorded 18, HES APC 29 and NICOR 24 events respectively. 12/18 (67%) of the HF/ACS events in the trial dataset were recorded by NICOR. CONCLUSION: Concordance between datasets was lower than anticipated and the HSD used could not straightforwardly replace current trial practices, nor directly identify protocol-defined CVS events. Further work is required to improve the quality of HSD and consider event definitions when designing clinical trials incorporating HSD.

Spatial release of masking in children and adults in non-individualized virtual environments.

The spatial release of masking (SRM) is often measured in virtual auditory environments created from head-related transfer functions (HRTFs) of a standardized adult head. Adults and children, however, differ in head dimensions and mismatched HRTFs are known to affect some aspects of binaural hearing. So far, there has been little research on HRTFs in children and it is unclear whether a large mismatch of spatial cues can degrade speech perception in complex environments. In two studies, the effect of non-individualized virtual environments on SRM accuracy in adults and children was examined. The SRMs were measured in virtual environments created from individual and non-individualized HRTFs and the equivalent real anechoic environment. Speech reception thresholds (SRTs) were measured for frontal target sentences and symmetrical speech maskers at 0° or ±90° azimuth. No significant difference between environments was observed for adults. In 7 to 12-year-old children, SRTs and SRMs improved with age, with SRMs approaching adult levels. SRTs differed slightly between environments and were significantly worse in a virtual environment based on HRTFs from a spherical head. Adult HRTFs seem sufficient to accurately measure SRTs in children even in complex listening conditions.

The spectrum of cardiovascular complications related to immune-checkpoint inhibitor treatment : Including myocarditis and the new entity of non inflammatory left ventricular dysfunction.

BACKGROUND: The full range of cardiovascular complications related to the use of Immune checkpoint inhibitors (ICI) is not fully understood. We aim to describe the spectrum of cardiovascular adverse events (cvAEs) by presenting our real-world experience of the diagnosis and management of these complications. METHODS: Two thousand six hundred and forty-seven (2647) patients were started on ICI treatment between 2014 and 2020. Data from 110 patients referred to the cardio-oncology service with a suspected cvAE was collected prospectively and analysed. RESULTS: Eighty-nine patients (3.4%) were confirmed to have cvAEs while on ICI therapy. Myocarditis was the most frequent event (33/89), followed by tachyarrhythmia (27/89), non-inflammatory left ventricular dysfunction (NILVD) (15/89) and pericarditis (7/89). Results from myocarditis and non-inflammatory left ventricular dysfunction cohorts were compared. Myocarditis and NILVD showed significant differences in respect toof troponin elevation, cardiac magnetic resonance abnormalities and ventricular function. Dual ICI therapy and other immune related adverse events were more frequently associated with myocarditis than NILVD. There was a significant difference in the median time from starting ICI treatment to presentation with myocarditis versus NILVD (12 vs 26 weeks p = 0.049). Through early recognition of myocarditis, prompt treatment with steroids and interruption of ICI, there were no cardiovascular in-hospital deaths. NILVD did not require steroid treatment and ICI could be restarted safely. CONCLUSIONS: The full spectrum of cardiovascular complications in patients with immune checkpoint inhibitors is much broader than initially described. Myocarditis remains the most frequent cvAE related to ICI treatment. A novel type of myocardial injury was observed and defined as Atrial tachyarrhythmias and NILVD were also frequent in this cohort. NILVD has a This differs fromdifferent presentation from ICI-related myocarditis, mainly usually presenting afterby the lack of inflammatory features on CMR and biomarkers and a later presentation in time.

Pharmacological strategies to reduce anthracycline-associated cardiotoxicity in cancer patients.

INTRODUCTION: Anthracycline chemotherapeutic agents are widely used in the treatment of hematological and solid tumors, working principally through DNA intercalation and topoisomerase II inhibition. However, they are also well known to have cardiotoxic sequelae, commonly denoted as a reduction in ejection fraction. Drug-associated cardiotoxicity remains a significant limiting factor in the use of anthracyclines. AREAS COVERED: In this review, we explore the potential mechanisms of anthracycline-associated cardiotoxicity, identifying high-risk cohorts and approaches to cardiovascular monitoring. The mechanisms through which cardiotoxicity occurs are complex and diverse, ultimately leading to increased oxidative stress, mitochondrial dysfunction, and subsequent cellular apoptosis. Many of the cardiotoxic effects of anthracyclines exhibit a dose-dependent cumulative relationship and are more apparent in patients with previously existing cardiovascular risk factors. Long-term cardiovascular monitoring and optimization of risk factors, prior to commencing treatment as well as beyond the time of treatment, is therefore essential. EXPERT OPINION: We discuss some of the pharmacological strategies proposed to mitigate anthracycline-associated cardiotoxicity as well as prevention strategies to reduce the burden of coexisting cardiovascular risk factors. We highlight methods of early detection of patient cohorts who are at increased risk of developing anthracycline-associated cardiotoxicity and identify potential avenues for further research.

Speech recognition with a hearing-aid processing scheme combining beamforming with mask-informed speech enhancement.

A signal processing approach combining beamforming with mask-informed speech enhancement was assessed by measuring sentence recognition in listeners with mild-to-moderate hearing impairment in adverse listening conditions that simulated the output of behind-the-ear hearing aids in a noisy classroom. Two types of beamforming were compared: binaural, with the two microphones of each aid treated as a single array, and bilateral, where independent left and right beamformers were derived. Binaural beamforming produces a narrower beam, maximising improvement in signal-to-noise ratio (SNR), but eliminates the spatial diversity that is preserved in bilateral beamforming. Each beamformer type was optimised for the true target position and implemented with and without additional speech enhancement in which spectral features extracted from the beamformer output were passed to a deep neural network trained to identify time-frequency regions dominated by target speech. Additional conditions comprising binaural beamforming combined with speech enhancement implemented using Wiener filtering or modulation-domain Kalman filtering were tested in normally-hearing (NH) listeners. Both beamformer types gave substantial improvements relative to no processing, with significantly greater benefit for binaural beamforming. Performance with additional mask-informed enhancement was poorer than with beamforming alone, for both beamformer types and both listener groups. In NH listeners the addition of mask-informed enhancement produced significantly poorer performance than both other forms of enhancement, neither of which differed from the beamformer alone. In summary, the additional improvement in SNR provided by binaural beamforming appeared to outweigh loss of spatial information, while speech understanding was not further improved by the mask-informed enhancement method implemented here.

Who is Right? A Word-Identification-in-Noise Test for Young Children Using Minimal Pair Distracters.

PURPOSE: Many children have difficulties understanding speech. At present, there are few assessments that test for subtle impairments in speech perception with normative data from U.K. children. We present a new test that evaluates children's ability to identify target words in background noise by choosing between minimal pair alternatives that differ by a single articulatory phonetic feature. This task (a) is tailored to testing young children, but also readily applicable to adults; (b) has minimal memory demands; (c) adapts to the child's ability; and (d) does not require reading or verbal output. METHOD: We tested 155 children and young adults aged from 5 to 25 years on this new test of single word perception. RESULTS: Speech-in-noise abilities in this particular task develop rapidly through childhood until they reach maturity at around 9 years of age. CONCLUSIONS: We make this test freely available and provide associated normative data. We hope that it will be useful to researchers and clinicians in the assessment of speech perception abilities in children who are hard of hearing or have developmental language disorder, dyslexia, or auditory processing disorder. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.17155934.

Temporal integration for amplitude modulation in childhood: Interaction between internal noise and memory.

It is still unclear whether the gradual improvement in amplitude-modulation (AM) sensitivity typically found in children up to 10 years of age reflects an improvement in "processing efficiency" (the central ability to use information extracted by sensory mechanisms). This hypothesis was tested by evaluating temporal integration for AM, a capacity relying on memory and decision factors. This was achieved by measuring the effect of increasing the number of AM cycles (2 vs 8) on AM-detection thresholds for three groups of children aged from 5 to 11 years and a group of young adults. AM-detection thresholds were measured using a forced-choice procedure and sinusoidal AM (4 or 32 Hz rate) applied to a 1024-Hz pure-tone carrier. All age groups demonstrated temporal integration for AM at both rates; that is, significant improvements in AM sensitivity with a higher number of AM cycles. However, an effect of age is observed as both 5-6 year olds and adults exhibited more temporal integration compared to 7-8 and 10-11 year olds at both rates. This difference is due to: (i) the 5-6 year olds displaying the worst thresholds with 2 AM cycles, but similar thresholds with 8 cycles compared to the 7-8 and 10-11 year olds, and, (ii) adults showing the best thresholds with 8 AM cycles but similar thresholds with 2 cycles compared to the 7-8 and 10-11 year olds. Computational modelling indicated that higher levels of internal noise combined with poorer short-term memory capacities in children accounted for the developmental trends. Improvement in processing efficiency may therefore account for the development of AM detection in childhood.