The Southern Medical Journal (SMJ) is the official, peer-reviewed journal of the Southern Medical Association. It has a multidisciplinary and inter-professional focus that covers a broad range of topics relevant to physicians and other healthcare specialists.

SMJ // Article

Original Article

Relationship between Systolic Ejection Time and Inflammation in End-Stage Heart Failure

Authors: Joel Gutovitz, MD, Jonathan Kutcher, MD, David Z. Cherney, MD, PhD, Yael Schiller, MD, Itzhak Gabizon, MD, Eran Keshet, BSc, Jordan Rimon, BSc, David Koren, MD, Vivek Rao, MD, PhD, Liza Grosman-Rimon, PhD

Abstract

Objectives: Systolic ejection time (SET) and systemic inflammation are two essential indicators of heart failure (HF) progression. We aimed to evaluate the associations between SET and inflammatory mediators in end-stage HF.

Methods: Participants included 16 patients with end-stage HF recruited from the Heart Failure Clinic at Toronto General Hospital and 16 healthy individuals free of any known cardiovascular disease. SET, end systolic pressure, and levels of inflammatory mediators were documented for each patient, and a Spearman rank correlation coefficient was performed to examine differences between patients with end-stage HF and healthy controls.

Results: The mean SET in patients with HF was shorter than in the healthy controls (283.5 ± 34.3 ms vs 330.1 ± 19.0 ms, P < 0.001). C-reactive protein (P = 0.001), macrophage inflammatory protein-1β (P = 0.041), macrophage-derived chemokine (P = 0.007), and cyclic guanosine monophosphate (P < 0.001) levels were negatively correlated with SET. The levels of other inflammatory mediators—granulocyte-stimulating factor, granulocyte-macrophage colony-stimulating factor, interleukin-8, macrophage inflammatory protein-1, macrophage inflammatory protein-1α, and tumor necrosis factor α—were not significantly correlated with SET.

Conclusions: We found that SET was significantly lower in patients with end-stage HF compared with healthy controls and that reduced SET correlated with increased levels of several inflammatory mediators in patients with HF. By better understanding the relationship between SET and inflammation in HF, a more thorough evaluation could lead to improved risk stratification among patients with HF. Future work should investigate the roles of SET and inflammation in HF.

This content is limited to qualifying members.

Existing members, please login first

If you have an existing account please login now to access this article or view purchase options.

Purchase only this article ($25)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.

References

1. Verbrugge FH, Guazzi M, Testani JM, et al. Altered hemodynamics and end-organ damage in heart failure: impact on the lung and kidney. Circulation 2020;142:998–1012.
 
2. Patel PA, Ambrosy AP, Phelan M, et al. Association between systolic ejection time and outcomes in heart failure by ejection fraction. Eur J Heart Fail 2020;22:1174–1182.
 
3. Alhakak AS, Teerlink JR, Lindenfeld J, et al. The significance of left ventricular ejection time in heart failure with reduced ejection fraction. Eur J Heart Fail 2021;23:541–551.
 
4. Aukrust P, Ueland T, Muller F, et al. Elevated circulating levels of C-C chemokines in patients with congestive heart failure. Circulation 1998;97:1136–1143.
 
5. Aukrust P, Ueland T, Lien E, et al. Cytokine network in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 1999;83:376–382.
 
6. Anand IS, Latini R, Florea VG, et al. C-reactive protein in heart failure: prognostic value and the effect of valsartan. Circulation 2005;112:1428–1434.
 
7. Albar Z, Albakri M, Hajjari J, et al. Inflammatory markers and risk of heart failure with reduced to preserved ejection fraction. Am J Cardiol 2022;167:68–75.
 
8. Chrysohoou C, Pitsavos C, Barbetseas J, et al. Chronic systemic inflammation accompanies impaired ventricular diastolic function, detected by Doppler imaging, in patients with newly diagnosed systolic heart failure (Hellenic Heart Failure Study). Heart Vessels 2009;24:22–26.
 
9. Biering-Sørensen T, Querejeta Roca G, Hegde SM, et al. Left ventricular ejection time is an independent predictor of incident heart failure in a community-based cohort. Eur J Heart Fail 2018;20:1106–1114.
 
10. Weissler AM, Harris WS, Schoenfeld CD. Systolic time intervals in heart failure in man. Circulation 1968;37:149–159.
 
11. Teerlink JR, Clarke CP, Saikali KG, et al. Dose-dependent augmentation of cardiac systolic function with the selective cardiac myosin activator, omecamtiv mecarbil: a first-in-man study. Lancet 2011;378:667–675.
 
12. Shen YT, Malik FI, Zhao X, et al. Improvement of cardiac function by a cardiac myosin activator in conscious dogs with systolic heart failure. Circ Heart Fail 2010;3:522–527.
 
13. Teerlink JR, Diaz R, Felker GM, et al. Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure. N Engl J Med 2021;384:105–116.
 
14. Patel PH, Nguyen M, Rodriguez R, et al. A novel mechanistic and therapeutic approach to chronic heart failure management. Cureus 2021;13:e12419.
 
15. Torre-Amione G, Kapadia S, Benedict C, et al. Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the Studies of Left Ventricular Dysfunction (SOLVD). J Am Coll Cardiol 1996;27:1201–1206.
 
16. Deswal A, Petersen NJ, Feldman AM, et al. Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine database from the Vesnarinone trial (VEST). Circulation 2001;103:2055–2059.
 
17. Murphy SP, Kakkar R, McCarthy CP, et al. Inflammation in heart failure: JACC state-of-the-art review. J Am Coll Cardiol 2020;75:1324–1340.
 
18. Tatara Y, Ohishi M, Yamamoto K, et al. Macrophage inflammatory protein-1beta induced cell adhesion with increased intracellular reactive oxygen species. J Mol Cell Cardiol 2009;47: 104–111.
 
19. Damås JK, Gullestad L, Aass H, et al. Enhanced gene expression of chemokines and their corresponding receptors in mononuclear blood cells in chronic heart failure—modulatory effect of intravenous immunoglobulin. J Am Coll Cardiol 2001;38:187–193.
 
20. Zhao D, Guallar E, Vaidya D, et al. Cyclic guanosine monophosphate and risk of incident heart failure and other cardiovascular events: the ARIC Study. J Am Heart Assoc 2020;9: e013966.
 
21. Francis SH, Corbin JD, Bischoff E. Cyclic GMP-hydrolyzing phosphodiesterases. Handb Exp Pharmacol 2009(191):367–408.
 
22. Lourenço P, Araújo JP, Azevedo A, et al. The cyclic guanosine monophosphate/B-type natriuretic peptide ratio and mortality in advanced heart failure. Eur J Heart Fail 2009;11: 185–190.
 
23. Emdin M, Aimo A, Castiglione V, et al. Targeting cyclic guanosine monophosphate to treat heart failure: JACC review topic of the week. J Am Coll Cardiol 2020;76:1795–1807.
 
24. Zuchi C, Tritto I, Carluccio E, et al. Role of endothelial dysfunction in heart failure. Heart Fail Rev 2020;25:21–30.
 
25. Tsai EJ, Kass DA. Cyclic GMP signaling in cardiovascular pathophysiology and therapeutics. Pharmacol Ther 2009;122:216–238.