Author + information
- Steffen E. Petersen, MD, DPhil, MPH∗ ()
- Advanced Cardiovascular Imaging, William Harvey Research Institute, National Institute for Health Research Cardiovascular Biomedical Research Unit at Barts, London, United Kingdom
- ↵∗Reprint requests and correspondence:
Prof. Steffen E. Petersen, Advanced Cardiovascular Imaging, William Harvey Research Institute, National Institute for Health Research Cardiovascular Biomedical Research Unit at Barts, Charterhouse Square, London EC1M 6BQ, United Kingdom.
Left ventricular noncompaction (LVNC) is characterized by a 2-layered appearance of the myocardium, with a thick inner trabeculated layer and a thin outer compacted myocardial layer. Many uncertainties remain with regard to its prevalence, pathogenesis, natural history, and the mechanisms leading to heart failure, malignant arrhythmias, and thromboembolic events. Dilated cardiomyopathy can lead to the same clinical picture described in LVNC patients. The little that is known about the prognosis of LVNC patients with nonischemic left ventricular (LV) dilation and systolic dysfunction is on the basis of small case series and is thus likely to be confounded by publication bias. Treatment approaches in LVNC patients are similar to those in dilated cardiomyopathy; however, because of a lack of evidence, there is no consensus as to whether the threshold to treat should be lower than for dilated cardiomyopathy with regard to anticoagulation or device implantation (implantable cardioverter-defibrillator, cardiac resynchronization therapy).
Stacey et al. (1) recently showed in a retrospective study that for a number of diagnostic cardiac magnetic resonance (CMR) criteria that were similar to but slightly modified compared with those in previously published studies, associations existed with prevalent (existing) heart failure and with incident (future) combined clinical events (death, heart failure readmission, embolic events, or ventricular arrhythmias).
In this issue of iJACC, Amzulescu et al. (2) further address an important question about the contribution of the extent of LV trabeculation to prognosis in dilated cardiomyopathy. In this prospective registry of 162 patients with dilated cardiomyopathy who presented with a spectrum of LV trabeculation extent (from little to excessive), a significant proportion fulfilled an imaging diagnosis of LVNC: 37% for CMR criteria from Petersen et al. (3) and 45% for CMR criteria from Jacquier et al (4). In these 162 patients with a median follow-up of 3.4 years, neither the Petersen (3) nor the Jacquier (4) criteria were independent predictors for major adverse cardiovascular events (MACE). Only LV ejection fraction and late gadolinium enhancement were independent predictors of MACE-free survival in multivariate analyses.
This study has potential clinical impact. This new information already provides some reassurance to clinicians and patients that management of LVNC does not require different strategies or treatment thresholds above the established ones for dilated cardiomyopathy; however, the study does not provide enough evidence for a definitive answer. One of the major limitations, which is appropriately acknowledged, is related to the small sample size and low event rates. We can only be 80% confident that event rates are not at least 50% different between patients with and without an imaging criterion for LVNC.
Future larger studies are required to confirm that smaller differences in event rates are not missed (false negative result). Effect sizes related to LV trabeculations are likely to be much smaller than 50%, as used for the sample size calculation in the report by Amzulescu et al. (2), given that patients with dilated cardiomyopathy are (presumably) undergoing optimal medical therapy.
Further controversies and uncertainties remain with regard to the best diagnostic approach. Which image modality and which diagnostic criterion should be used, and should the measurements be performed during end diastole or end systole? Fractal dimension analysis, introduced by Captur et al. (5), is a promising method of obtaining a more objective assessment of endocardial complexity; however, even this approach is not without its limitations, because it does not take into account the thickness of the compacted myocardium, which may be a very important phenotypic marker of real (but rare) disease. In a recent editorial in iJACC (6), I emphasized the need to interpret any measure of the degree of LV trabeculations in the clinical context (to establish the pre-test probability) when considering an imaging diagnosis of LVNC.
There is a cost to labeling patients with a new diagnosis of LVNC when there is not enough evidence to suggest that the natural history compared with a reference population is different. This can unnecessarily create patient anxiety and can have significant implications for health care resources. To this end, Zemrak et al. (7) recently demonstrated that the extent of trabeculations does not predict clinically relevant adverse cardiac remodeling in an asymptomatic population cohort study. This information should guide clinical decision making in the common scenario of identifying patients with marked LV trabeculation and low pre-test probability of LVNC, in that there is no clear need for follow-up imaging or pharmacotherapy in these patients. The study by Amzulescu et al. (2) extends this work by showing that in patients with dilated cardiomyopathy, marked LV trabeculations do not appear to modify the MACE-free survival.
Given the remaining uncertainties concerning LVNC, it is no surprise that the American Heart Association and European Society of Cardiology have differing opinions as to whether LVNC should be a distinct cardiomyopathy. Do trabeculations perhaps just represent an epiphenomenon? Further research is warranted to answer this question, but until more data become available, it seems that there is no convincing evidence to suggest that the degree of trabeculations has incremental prognostic value in asymptomatic low-risk populations and in dilated cardiomyopathy.
↵∗ Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
This work forms part of the research contributing to the translational research portfolio of the Cardiovascular Biomedical Research Unit at Barts, which is supported and funded by the National Institute for Health Research. Prof. Petersen has received consultant fees from Circle Cardiovascular Imaging.
- American College of Cardiology Foundation
- Stacey R.B.,
- Andersen M.M.,
- St. Clair M.,
- Hundley W.G.,
- Thohan V.
- Amzulescu M.-S.,
- Rousseau M.F.,
- Ahn S.A.,
- et al.
- Petersen S.E.,
- Selvanayagam J.B.,
- Wiesmann F.,
- et al.
- Jacquier A.,
- Thuny F.,
- Jop B.,
- et al.
- Captur G.,
- Muthurangu V.,
- Finocchiaro G.,
- et al.
- Petersen S.E.
- Zemrak F.,
- Ahlman M.A.,
- Captur G.,
- et al.