Q. Smith

Background: Dilated Cardiomyopathy (DCM) significantly reduces life expectancy and quality of life, with 1-year and 5-year survival rates of 70%-75% and 50%, respectively[1]. Remodeling of the left ventricle (LV) is central to DCM, driven by cardiomyocyte breakdown and pro-inflammatory pathways[2]. Treatment can slow or reverse tissue remodeling[3, 4, 5], which predicts prognosis[6]. The renin-angiotensin-aldosterone-system (RAAS) plays a key role in ventricular remodeling[3], but other mechanisms remain unclear[6].

Methods: PubMed’s database was used as the primary source of literature for this review. Keywords included “dilated cardiomyopathy,” “myocardial remodeling,” and “reverse remodeling.” Results were limited to articles published within the last five years.

Results: Research in myocardial remodeling has largely focused on understanding molecular markers and the clinical impact of treatments on tissue adaptation and stress tolerance. In the leading drug-therapy, Sacubitril/Valsartan combination therapy (SVCT), stabilization of cellular Ca2+ levels during periods of high stress contributes to cardioprotective effects via decreased expression of calmodulin-dependent protein kinase II[3]. SVCT’s impact on natriuretic peptide levels is another mediating factor for its contribution to positive cardiac remodeling[7]. Specifically, the resulting decrease in N-terminal pro B-type natriuretic peptide (NT-proBNP) levels were observed to be predictive for reverse-remodeling in HF patients on SVCT[7]. From a different drug class, Lisinopril, an Angiotensin-Converting-Enzyme (ACE) inhibitor, reduces dendritic cell infiltration and tissue proinflammatory cytokine levels in a murine myocardial infarction model[4]. Shifting focus to device-based therapies, left ventricular assist devices (LVADs) result in mechanical unloading of the LV. In some patients, this can result in myocardial recovery sufficient to negate the need for cardiac transplantation[8]. This is referred to as a “bridge to recovery” rather than “bridge to transplant”[8]. To achieve this, a 2020 trial used LVAD-induced LV unloading in conjunction with targeted pharmacologic therapy (ACE inhibitors + Angiotensin-Receptor-Blockers) to reduce risk of mortality by 47%, where more than half of patients involved in the trial achieved myocardial recovery sufficient to meet criteria for explantation of their LVAD device[9].

Conclusions: Recent research in this field offers valuable insights for clinicians in tailoring treatment plans for individual patients. Future investigations aim to explore novel drug designs targeting newly identified molecular pathways and the potential of machine learning algorithms to optimize therapeutic outcomes on a case-by-case basis. These endeavors hold promise for increasing the number of heart failure patients who can recover without the need for cardiac transplantation.

Works Cited:

1.  Reichart D, Magnussen C, Zeller T, Blankenberg S. Dilated cardiomyopathy: from epidemiologic to genetic phenotypes. Journal of Internal Medicine. 2019;286(4):362-372. doi:https://doi.org/10.1111/joim.12944
2. Schultheiss HP, Fairweather D, Caforio ALP, et al. Dilated Cardiomyopathy. Nature Reviews Disease Primers. 2019;5(1). doi:https://doi.org/10.1038/s41572-019-0084-1
3.  Eiringhaus J, Wünsche CM, Tirilomis P, et al. Sacubitrilat reduces pro‐arrhythmogenic sarcoplasmic reticulum Ca ²⁺ leak in human ventricular cardiomyocytes of patients with end‐stage heart failure. ESC Heart Failure. 2020;7(5):2992-3002. doi:https://doi.org/10.1002/ehf2.12918
4. Ma Y, Yuan J, Hu J, Gao W, Zou Y, Ge J. ACE inhibitor suppresses cardiac remodeling after myocardial infarction by regulating dendritic cells and AT2 receptor-mediated mechanism in mice. Biomedicine & Pharmacotherapy. 2019;114:108660. doi:https://doi.org/10.1016/j.biopha.2019.108660
5. Jarkovská D, Miklovič M, Švíglerová J, et al. Effects of Trandolapril on Structural,
6. Contractile and Electrophysiological Remodeling in Experimental Volume Overload Heart Failure. Frontiers in Pharmacology. 2021;12. doi:https://doi.org/10.3389/fphar.2021.729568
7. Kimura Y, Okumura T, Morimoto R, et al. A clinical score for predicting left ventricular reverse remodelling in patients with dilated cardiomyopathy. ESC heart failure. 2021;8(2):1359-1368. doi:https://doi.org/10.1002/ehf2.13216
8. Yamamoto M, Ishizu T, Sato K, et al. Longitudinal Changes in Natriuretic Peptides and Reverse Cardiac Remodeling in Patients with Heart Failure Treated with Sacubitril/Valsartan Across the Left Ventricular Ejection Traction Spectrum. International Heart Journal. 2023;64(6):1071-1078. doi:https://doi.org/10.1536/ihj.23-407
9. Briasoulis A, Ruiz Duque E, Mouselimis D, Tsarouchas A, Bakogiannis C, Alvarez P. The role of renin-angiotensin system in patients with left ventricular assist devices. Journal of the Renin-Angiotensin-Aldosterone System. 2020;21(4):147032032096644. doi:https://doi.org/10.1177/1470320320966445
10. Rayan Yousefzai, Michela Brambatti, Tran HA, et al. Benefits of Neurohormonal Therapy in Patients With Continuous-Flow Left Ventricular Assist Devices. ASAIO journal. 2020;66(4):409-414. doi:https://doi.org/10.1097/mat.0000000000001022