Fat in the Heart! How do we find it?
As surgeons we can see fat on the inside of the body! Most others, from physicians to radiologists to lay people just know about fat being inside the body. So, imagine our excitement when we discovered that fat is revealed very nicely by a simple technique called Raman Spectroscopy! More about CV Raman, the 1930 Nobel Prize winner, who intuited the concept behind spectroscopy in the 1920s and established Raman Spectroscopy in 1928.
I blogged about the detection of fat -
Lipids in the Heart – Vibrational Spectroscopy to the Fore
Adipocytes, fat and lipids are difficult to detect, delineate and quantify with conventional histopathology (Ref). This is more so when these are interspersed with normal cellular architecture in a densely muscular structure like the heart (1). Epicardial Adipose Tissue (EAT) has been increasingly recognized as a causative factor in a variety of cardiac conditions, due to the lack of a clear capsular delineation between adipose tissue and myocardium.
Lipid detection is not done routinely. Fat quantification, delineation and distribution are difficult to assess pre-operatively and even intra-operatively. A recently published a review on increased Epicardial Adipose Tissue (EAT) in atria of patients with atrial fibrillation (2) suggests a clear association. So, fat is probably a tissue biomarker for AF. However, what is the threshold? How much? What kind? Where?
We often see fat on the epicardial surface of the heart and have made observations about how epicardial coronary arteries are more prone to atherosclerotic plaques. We often note that coronary arteries are often spared these obstructive lesions in their intra-myocardial course. So, many researchers have postulated that EAT might carry mediators of "badness", adipokines or messengers that predispose to plaque formation. Near-Infrared Autofluorescence in Atherosclerosis by Albadhdadi, et al (3) showed that ceroid elements in plaques are easily detected by specialized techniques such as NIRS.
Increased lipid accumulation in the myocardium has been associated with myocardial disarray, fibrosis and apoptosis, leading to heart failure and atrial fibrillation (4,5). Several studies have highlighted the use of EAT measurement in predicting outcomes after catheter ablation for paroxysmal or persistent atrial fibrillation (5,6). Peri-atrial EAT volume is greater in patients with atrial fibrillation and is associated with recurrence after catheter ablation (6–9). EAT volume is associated with atrial fibrillation persistence independent of other risk factors or BMI (10). In any case, fat in the heart is key and our very exciting findings relate to epicardial fat in the atrial appendages!
Fat, even when NOT clearly visible to the educated surgical eye, can be detected with Vibrational Spectroscopy. This is extremely accurate and quick. Not only that, we can differentiate different kinds of fat! Lipids are everywhere in biological tissues, from cell membranes to the interior of cells and the space in between them.
What is even more compelling is that we can detect endocardial fat signatures with Raman Spectroscopy when it is not clearly visible to the naked eye. When we deploy multi-modal spectroscopy, we can look at the lipids with some degree of sophistication into lipid families, types, lipoproteins, and more.
A lot of credit for this experimental work goes to our wonderful medical students, James Grant and Sarina Moshfegh, our recently graduated PhD candidate Dr Varun Sharma and Prof Shekhar Kumta, who helped us along the way.
We have been collecting and biobanking fresh frozen cardiac tissue that is discarded during cardiac surgery procedures and used them to build this story! More about that in the next story!
1. Iacobellis, G. Epicardial adipose tissue in contemporary cardiology. Nat Rev Cardiol 19, 593–606 (2022). https://doi.org/10.1038/s41569-022-00679-9.
2. Krishnan, A.; Chilton, E.; Raman, J.; Saxena, P.; McFarlane, C.; Trollope, A.; Kinobe, R.; Chilton, L. Are Interactions between Epicardial Adipose Tissue, Cardiac Fibroblasts and Cardiac Myocytes Instrumental in Atrial Fibrosis and Atrial Fibrillation?. Cells 2021, 10(9), 2501; https://doi.org/10.3390/cells10092501.https://www.mdpi.com/2073-4409/10/9/2501
3. Albaghdadi MS, Ikegami R, Kassab. MB, Gardecki JA, et al: Near-Infrared. Autofluorescence Associates with Ceroid and Is Generated by Oxidized Lipid-Induced Oxidative Stress. AthThromVascBiol.2021;41:e385-e398. doi: 10.1161/ATVBAHA.120.315612.
4. .Neeland, I. J., Poirier, P. & Després, J. P. Cardiovascular and metabolic heterogeneity of obesity: clinical challenges and implications for management. Circulation 137, 1391–1406 (2018).
5. Oikonomou, E. K. & Antoniades, C. The role of adipose tissue in cardiovascular health and disease. Nat. Rev. Cardiol. 16, 83–99 (2019).
6. Tsao, H. M. et al. Quantitative analysis of quantity and distribution of epicardial adipose tissue surrounding the left atrium in patients with atrial fibrillation and effect of recurrence after ablation. Am. J. Cardiol. 107, 1498–1503 (2011).
7. Chao, T.-F. et al. Epicardial adipose tissue thickness and ablation outcome of atrial fibrillation. PLoS ONE 8, e74926 (2013).
8. Kocyigit, D. et al. Periatrial epicardial adipose tissue thickness is an independent predictor of atrial fibrillation recurrence after cryoballoon-based pulmonary vein isolation. J. Cardiovasc. Comput. Tomogr. 9, 295–302 (2015).
9. Masuda, M. et al. Abundant epicardial adipose tissue surrounding the left atrium predicts early rather than late recurrence of atrial fibrillation after catheter ablation. J. Interv. Card. Electrophysiol. 44, 31–37 (2015).
10. Iacobellis, G., Zaki, M. C., Garcia, D. & Willens, H. J. Epicardial fat in atrial fibrillation and heart failure. Horm. Metab. Res. 46, 587–590 (2014).