This webinar recording can be found here.
Questions & Answers
Q: Is GLS by CMR comparable to echo?
A: There are different methods of obtaining deformation data using Cardiac MRI (CMR). Myocardial tagging (MT) is an established method of measuring strain which has been extensively validated (Swoboda J. Magn. Reson. Imaging, 2014). Currently, a number of MT-based techniques are available for strain evaluation (spatial modulation of magnetization (SPAMM); Displacement encoding with simulated echoes (DENSE); and more recently fast strain encoding (SENC)) – the latter allowing strain data acquisition from a single heart beat. In the case presented we demonstrated the use of Feature tracking (FT) CMR which unlike myocardial tagging methods mentioned above does not require the use of a dedicated sequence and can be performed on previously acquired cine imaging. Global longitudinal strain (GLS) obtained from FT CMR and speckle tracking echocardiography are comparable, but the values are not interchangeable. Feature tracking CMR allows acquisition of deformation parameters such as GLS though tissue voxel motion tracking, a process which is analogous to speckle tracking performed with echocardiography. A number of studies have shown good correlation with speckle tracking echocardiography (Onishi et al. J Am Soc Echocardiogr. 2015; Obokata et al, Eur Heart J Cardiovasc Imaging. 2016). Furthermore, meta-analysis data (Vo et al, JACC Cardiovasc Imaging. 2018) looking at the normal range of GLS obtained from FT CMR in healthy subjects showed a mean GLS -20.1% (95% CI: -20.9% to -19.3%) which is comparable to normal GLS range from speckle tracking echocardiography.
Q: How frequent you do CMR, is it yearly or every 6 months?
A: Current guidelines propose the use of echocardiography as a first line test for evaluation of LV function in the context of trastuzumab-induced cardiotoxicity monitoring, with 3 monthly monitoring during treatment (2016 ESC position statement European Heart Journal (2016)37, 2768–2801). The argument made in the first case presented, was that the superior precision (test: re-test variability in LVEF estimation) associated with CMR allows us to avoid the fluctuations in LVEF and unnecessary treatment interruptions, seen particularly in patients with poor echocardiographic windows, as shown in this case. It is worth highlighting that the CMR studies performed on this patient, were focused, short CMR studies (under 15 minutes duration, no requirement for contrast administration) focusing on cardiac function.
Q: Any experience with CMR- strain software?
A: The software used in our department is CVI42 (Circle Cardiovascular Imaging Inc, Calgary, Canada). Strain analysis is primarily used as a research tool rather than for clinical purposes. As with speckle tracking echocardiography inter-vendor differences have been reported among different CMR analysis software (Barreiro-Perez et al, Eur Radiol, 2018). Among deformation parameters, left ventricular GLS appears to have reasonable inter-vendor agreement in some reports (Gertz et al, PLoS One. 2018).
Q: Which software was used to measure strain in this case?
A: As above.
Q: I think We should implement CMR prior starting chemotherapy as suggested. But the question come of the time interval? And would you abandon Echo?
A: As above.
Q: Do you have any experience with immune check point inhibitors medication?
A: The cardio oncology service at the Barts Heart Centre in actively involved in the care of patients receiving immune checkpoint inhibitors (ICI) for both the surveillance and management of ICI-related cardiotoxicity - the case presented as part of the webinar was an example. ICI myocarditis is the most significant cardiotoxicity and although its incidence of 1% makes it relatively uncommon compared to the other ICI-induced complications, it carries the highest risk of mortality at 40%. The presentation is varied, and can include asymptomatic elevations in serum troponin on one hand, to decompensated cardiac failure and the accumulation of pericardial effusions, and on the most severe end of the spectrum, cardiogenic shock and serious arrhythmias such as advanced conduction disease or ventricular tachycardia. High dose corticosteroids are the mainstay of therapy, with reports or case series of success with intravenous immunoglobulin, myocophenolate, infliximab, anti-thymocyte globulin, plasmapheresis, atemtuzumab, and abatacept in those refractory to corticosteroids. The meta-analysis by Wang et al in JAMA Oncology in 2018, analysis by Zhang in EHJ in 2020, and review by Palasakas et al in JAHA in 2020 are useful references.
Q: In patients with impaired cardiac function, how do you differentiate myocarditis from infarction?
A: Contrast enhanced CMR is particularly helpful for differentiating myocarditis from infarction. The characteristic pattern of late gadolinium enhancement (LGE) due to infarction is either subendocardial or transmural following a coronary artery territory. In contrast, the characteristic pattern of LGE due to myocarditis is patchy or multifocal in a subepicardial or mid wall distribution, often involving (but not limited to) the lateral wall. In addition, T2 weighted imaging and parametric mapping techniques including T1 and T2 mapping offer the ability to detect and quantify myocardial oedema, enabling an assessment of active myocardial inflammation.
Q: Have you seen many cases LGE - and myocardial fibrosis by endomyocardial biopsy?
A: Endomyocardial biopsy (EMB) remains the gold standard for definite myocarditis, as outlined by the European Society of Cardiology (ESC) Working Group on Myocardial and Pericardial Diseases position paper in 2013. Non invasive imaging techniques such as CMR offer value for diagnosis especially in centres where there are state-of-the-art facilities and expertise as they may obviate the requirement for an invasive biopsy, and also can be performed serially to track disease and response to treatments. As with many centres in Europe, EMB is generally performed second line following CMR in conjunction with clinical, biochemical and immunological markers. In addition, where systemic toxicity secondary to immunotherapies is seen, extra-cardiac biopsy may yield diagnostic utility and reduce risk. In the important analysis of ICI myocarditis patients provided by Zhang et al in EHJ this year, the diagnosis of myocarditis included both EMB-proven and clinically proven (per ESC criteria in the 2013 position paper) cases. However, in all the patients who underwent both CMR and EMB, 98% had abnormal histopathology (lymphocytic infiltration); conversely, of this subset of patients with pathology-proven ICI myocarditis, only 64% demonstrated abnormal CMR tissue characterisation (LGE or increased T2-weighted STIR signal). Zhang et al therefore advocate for broader use of EMB within their diagnostic algorithm, especially if the T2-weighted STIR signal is normal.
Q: How sensitive is cardiac biopsy in ICI myocarditis?
A: As above.
Q: Checkpoint inhibitors are now being used in refractory pediatric solid tumors. What do we know about CMR in pediatric checkpoint induced myocardial toxicity or inflammation?
A: To our knowledge, there remains a paucity of data around ICI myocarditis and its incidence, mortality, diagnosis, and CMR phenotype within the paediatric population in the literature. Furthermore, whilst the utility of CMR in myocarditis has been extrapolated to paediatric patients, mapping techniques have not been systematically analysed in this age group. Cornicelli et al have provided an analysis of a small cohort of childrenwith myocarditis which suggests abnormalities in native T1 and T2 mapping and extracellular volume (ECV) are associated with a high sensitivity and specificity for the diagnosis of myocarditis. However, it is evident that further research into the utility of CMR in ICI myocarditis in children will be required to better understand the entity.
Q: LGE negative I meant
A: As above.
Q: If this patient developed cardiomyopathy with systolic dysfunction, would you give him 5FU?
A: There is plenty to be considered in this situation. Firstly, it would depend on the degree of his systolic dysfunction alongside his cardiac symptoms. For patients with complex cardiac histories, our usual practice is to discuss them in our dedicated Cardio-Oncology MDTs, where detailed discussions about the potential risks and benefits of 5FU is addressed in the presence of oncologists and cardiologists. If deemed suitable, our potential management strategy would include optimizing heart failure treatment with ACE-I and Beta blockers, and commencing medications such as calcium channel blockers and nitrates to reduce the likelihood of coronary artery vasospasm. Careful cardiac monitoring in cardio-oncology clinics are essential for such patients, although left ventricular dysfunction is a less common complication than coronary spasm with fluoropyrimidine chemotherapy agents.
Questions answered during the webinar:
Q: Do you have any pointers on the use of CMR in pediatric oncology patients?
Q: Could it be possible to combine myostrain with T2 mapping in cardio-oncology?
Q: Which region we should focus for edema evaluation? Septum?
Q: Thank you for these presentations. What are the best methods for T1/T2 mapping on CMR images?
Q: For edema evaluation it would be interesting to do longitudinal acquisitions?
Q: My concern is about the reason of the myocarditis such in HIV for example, is it the agents or infections. CMR could help diagnose myocarditis but not the etiology that affects the management?