Predicting left ventricular functional recovery after transcatheter aortic valve implantation with computed tomography-derived extracellular volume

European Heart Journal - Cardiovascular Imaging, vol. 22, pp. 186–187

Abstract

This editorial refers to ‘CTA-derived extracellular volume fraction predicts early recovery of left ventricular systolic function after transcatheter aortic valve replacement’, by D. Han et al., pp. 179–185. Aortic stenosis (AS) has a high prevalence, and comprised 41.2% of individuals referred for echocardiography in a large, contemporary registry.1 The outcome of severe, symptomatic AS is poor when managed medically without interventional treatment, and mortality approaches 50% in the first twelve months. Transcatheter aortic valve implantation (TAVI) has become the treatment of choice for inoperable and high-risk patients with severe AS, and the benefits of TAVI include: increased survival, symptomatic improvement and left ventricular (LV) systolic function improvement. LV systolic function, however, does not improve in all recipients of TAVI, despite effective relief of ventricular pressure overload.2 TAVI recipients who fail to improve their LV ejection fraction (LVEF) post-procedure, experience a worse long-term prognosis,3 although this has not been a consistent finding across all studies.2 The underlying mechanisms of failure to improve LVEF after TAVI are likely multifactorial, including epicardial coronary artery disease (which is a common comorbidity in patients with calcific AS) and AS-associated LV myocardial fibrosis.4 Progressive AS causes LV pressure overload, and the LV responds appropriately with adaptive hypertrophy to normalize wall stress. Hypertrophy, however, eventually becomes maladaptive, which is a pathological process accompanied by myocardial fibrosis. Both diffuse, reactive interstitial fibrosis and more localized replacement fibrosis (in response to cardiomyocyte apoptosis) are seen in severe AS-related maladaptive hypertrophy. The presence of myocardial fibrosis has been linked to impaired recovery of LVEF after surgical aortic valve replacement (AVR), and this mechanism is also likely at play in the context of TAVI.5 Myocardial fibrosis (both reactive and replacement) increases the extracellular volume fraction (ECV), i.e. the fraction of myocardium which is extracellular. Increased ECV impacts on LVEF recovery after AVR6 and on survival post-AVR and post-TAVI.7 The measurement of ECV is more commonly performed with cardiac magnetic resonance (CMR) imaging,8 but ECV can also be derived from computed tomography (CT) data (ECVCT).9 ECVCT is an attractive parameter due to the fact that it can be estimated from routine pre-TAVI CT, when performed for procedural planning. ECVCT has shown robust correlation with CMR ECV, and it has also been validated against myocardial histology in AS. While ECVCT data are therefore readily available from routine pre-TAVI CT scans, its ability to predict LVEF recovery after the procedure has not hitherto been examined. In the current issue of the journal, Han et al.10 investigated the utility of ECVCT in 109 TAVI patients with impaired LV systolic function pre-procedure (LVEF < 50%). Delayed, electrocardiogram-gated post-contrast CT was performed 5 min after contrast administration. Global LV ECVCT was subsequently measured from the interventricular septum and lateral wall of the LV by manually drawing regions of interest. Low intra- and inter-observer variability was demonstrated for ECVCT, supporting the reproducibility of the technique. An increase of >10% in LVEF after TAVI was defined as a significant improvement in systolic function. Baseline ECVCT values were higher in TAVI recipients who did not recover LV systolic function at a median of 43 days of follow-up, suggesting that ECVCT can predict early LVEF improvement after TAVI. Myocardial ECV may be increased by aetiologies other than extracellular fibrosis, e.g. by cardiac amyloidosis, where fibrils accumulate in and expand the extracellular space.9 Transthyretin cardiac amyloidosis (ATTR) is especially common in the elderly, and in patients with severe AS. A prevalence of up to 16% has been reported in TAVI recipients.9 The frequency of ATTR in AS patients considered for TAVI, is higher than expected by age alone, thereby suggesting that the pathophysiologies of these two conditions are in some way intertwined. The co-existence of severe AS and ATTR may act synergistically to impair functional LV recovery, although the exact nature of the interplay between them has not been established. The authors of the current study suggest that an ECVCT of >40% indicates cardiac amyloid, but an ECVCT greater than 33.7% provided a sensitivity of 100% and a specificity of 93.8% for diagnosing ATTR in AS patients in a previous analysis.9 It is therefore conceivable that a substantial proportion of the patients in the current study have underlying ATTR, which would have increased or contributed to the increase in ECVCT, and also to their impaired LVEF response. The measurement of LVEF post-procedure was performed at an early stage, which is appropriate since about 50% of patients recover LVEF soon after TAVI.2 It would however, have been intriguing to know what the course of LVEF evolution in the longer run was, and how this relates to ECVCT at baseline. Identification of patients who will not adequately recover LV systolic function post-TAVI can potentially be performed with ECVCT. This begs the question of how calculation of this parameter pre-procedure could change clinical management. If the co-existence of ATTR could be demonstrated, it may be addressed with novel therapies (e.g. the TTR tetramer stabilizer tafamidis, which has shown the ability to decrease mortality, heart failure hospitalization and improve symptomatology). A second possibility is the use of conventional anti-failure therapies to improve LVEF post-TAVI, and finally, ECVCT may serve as a marker for earlier intervention in AS patients, i.e. at a stage before irreversible fibrosis or functional impairment has developed. The utility of ECVCT as a biomarker in TAVI candidates will require data to demonstrate its impact on hard outcomes, and not only improvement of LVEF, since the recovery of LVEF post-TAVI has not been consistently associated with improved prognosis. Even though ECVCT-based guidance of management in patients with severe AS will require further study, it appears to be a very promising imaging marker in those being considered for TAVI. Conflict of interest: The Department of Cardiology of Leiden University Medical Centre received research grants from Abbott Vascular, Bayer, Biotronik, Bioventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare and Medtronic. V.D. received speaker fees from Abbott Vascular, MSD, Medtronic, Edwards Lifesciences and GE Healthcare. J.J.B. received speaker fees from Abbott Vascular. The remaining author has nothing to disclose. The opinions expressed in this article are not necessarily those of the Editors of EHJCI, the European Heart Rhythm Association or the European Society of Cardiology.

Authors 3

1. Pieter van der Bijl Aachen Department of Cardiology, Heart Lung Centre

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Cardiology, Heart Lung Centre, Leiden University Medical Centre, Albinusdreef 2, 2300 RC Leiden, The Netherlands

2. Victoria Delgado Aachen Department of Cardiology, Heart Lung Centre

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Cardiology, Heart Lung Centre, Leiden University Medical Centre, Albinusdreef 2, 2300 RC Leiden, The Netherlands

3. Jeroen Joost Bax corresponding Aachen Department of Cardiology, Heart Lung Centre

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Cardiology, Heart Lung Centre, Leiden University Medical Centre, Albinusdreef 2, 2300 RC Leiden, The Netherlands