Cardiac contractility modulation: a new treatment option for chronic heart failure in Poland

The Akt plays an important role in regulating cardiac growth, myocardial angiogenesis, and cell death in cardiac myocytes. However, there are few studies to focus on the responses of the Akt pathway to cardiac contractility modulation (CCM) in a chronic heart failure (HF) model. In this study, the effects of CCM on the treatment of HF in a rabbit model were investigated. Thirty six-month-old rabbits were randomly separated into control, HF, and CCM groups. The rabbits in HF and CCM groups were pressure uploaded, which can cause an aortic constriction. Then, CCM was gradually injected to the myocardium of rabbits in the CCM group, and this process lasted for four weeks with six hours per day. Rabbit body weight, heart weight, and heart beating rates were recorded during the experiment. To assess the CCM impacts, rabbit myocardial histology was examined as well. Additionally, western blot analysis was employed to measure the protein levels of Akt, FOXO3, Beclin, Pi3k, mTOR, GSK-3β, and TORC2 in the myocardial histology of rabbits. Results showed that the body and heart weight of rabbits decreased significantly after suffering HF when compared with those in the control group. However, they gradually recovered after CCM application. The CCM significantly decreased collagen volume fraction in myocardial histology of HF rabbits, indicating that CCM therapy attenuated myocardial fibrosis and collagen deposition. The levels of Akt, FOXO3, Beclin, mTOR, GSK-3β, and TORC2 were significantly downregulated, but Pi3k concentration was greatly upregulated after CCM utilization. Based on these findings, it was concluded that CCM could elicit positive effects on HF therapy, which was potentially due to the variation in the Pi3k/Akt signaling pathway.

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Therapy With Cardiac Contractility Modulation Electrical Signals Improves Left Ventricular Function and Remodeling in Dogs With Chronic Heart Failure

Journal of the American College of Cardiology ◽

10.1016/j.jacc.2006.10.082 ◽

2007 ◽

Vol 49 (21) ◽

pp. 2120-2128 ◽

Cited By ~ 73

Author(s):

Makoto Imai ◽

Sharad Rastogi ◽

Ramesh C. Gupta ◽

Sudhish Mishra ◽

Victor G. Sharov ◽

...

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Left Ventricular Function ◽

Ventricular Function ◽

Cardiac Contractility ◽

Left Ventricular ◽

Cardiac Contractility Modulation ◽

Electrical Signals

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The assessment of left ventricular myocardial work in patients with chronic heart failure receiving cardiac contractility modulation therapy

European Heart Journal ◽

10.1093/eurheartj/ehab724.0135 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

S Dobrovolskaya ◽

M Saidova ◽

A Safiullina ◽

T Uskach ◽

A Belevskaya ◽

...

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Ejection Fraction ◽

Nyha Class ◽

Cardiac Contractility ◽

Left Ventricular ◽

Cardiac Contractility Modulation ◽

Device Implantation ◽

Echocardiographic Parameters ◽

Global Work

Abstract Introduction A new non-invasive technology for the assessment of left ventricular myocardial work (LVMW) is based on speckle-tracking echocardiography and considers LV pressure. Changes in LVMW are described in patients with different cardiovascular diseases. In patients with chronic heart failure (CHF), LVMW is associated with long-term prognosis and favorable response to cardiac resynchronization therapy. Purpose To study echocardiographic parameters, including LVMW, in patients with CHF receiving cardiac contractility modulation therapy. Methods The study included 40 patients (31 men and 7 women) aged 60.5 [55.0; 66.0] years with heart failure with reduced ejection fraction (NYHA class II or III) in combination with atrial fibrillation. Before implantation of cardiac contractility modulation (CCM) device and 2, 6 and 12 months after, the patients underwent transthoracic echocardiography with an assessment of the main structural and functional parameters. Also, initially and after 12 months of CCM therapy, an assessment of global longitudinal strain (GLS) and LVMW was performed (global work index (GWI), global constructive work (GCW), global wasted work, global work efficiency (GWE)). Results Initially, the patients included in the study had enlarged left heart chambers and decreased left ventricular ejection fraction (LVEF). CCM therapy was accompanied by significant increase in LVEF from 30.0 [26.5; 37.0]% before device implantation up to 34.4 [27.0; 40.0]% (p=0.016) after 2 months and up to 38.0 [30.5; 42.0]% (p<0.01) after 6 months of treatment. One year after device implantation, a significant increase in LVEF was maintained as compared with initial data (39 [31; 45]%, p<0.01). We also analyzed the dynamics of echocardiographic parameters depending on etiology of CHF (ischemic and non-ischemic). As in general group of patients regardless of CHF etiology there was a significant increase in LVEF, that reached maximum values after 12 months of therapy (36 [30; 42]% in group with ischemic etiology, p<0.01 and 37 [30; 45]% in group with non-ischemic etiology, p<0.01). The assessment of GLS before and 12 months after device implantation revealed no significant dynamics (−7 [−9; −4]% and −8 [−9; −5]%, p=0.93). However, we observed significant changes in LVMW: an increase in GWI from 429 [332; 744] to 635 [401; 815] mm Hg% (p=0.01) and GWE (from 73 [68; 79] to 74 [70; 87] %, p=0.02) due to an increase in GCW (from 791 [530; 1031] to 836 [708; 1109] mm Hg%, p=0.03). Conclusions A significant increase in LVEF, GWI and GWE in patients with CHF (NYHA class II or III) receiving CCM therapy indicates an improvement in LV systolic function and the effectiveness of CCM therapy. The modern echocardiographic technologies open great opportunities for detailed assessment of the effectiveness of treatment of patients with CHF, including the use of CCM devices. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministry of Health of Russian Federation

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Cardiac Contractility Modulation Attenuate Myocardial Fibrosis by Inhibiting TGF-β1/Smad3 Signaling Pathway in a Rabbit Model of Chronic Heart Failure

Cellular Physiology and Biochemistry ◽

10.1159/000445624 ◽

2016 ◽

Vol 39 (1) ◽

pp. 294-302 ◽

Cited By ~ 18

Author(s):

Feifei Zhang ◽

Yi Dang ◽

Yingxiao Li ◽

Qingqing Hao ◽

Rong Li ◽

...

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Signaling Pathway ◽

Myocardial Fibrosis ◽

Cardiac Contractility ◽

Rabbit Model ◽

Cardiac Contractility Modulation ◽

Protein Levels ◽

Collagen Iii ◽

Tgf Β1

Backgroun/Aims: To explore the effect of cardiac contractility modulation (CCM) on myocardial fibrosis in heart failure and to investigate the underlying mechanism. Methods: Rabbits were randomly divided into sham group, HF group and CCM group. A rabbit model of chronic heart failure (CHF) was induced 12 weeks after aortic constriction by pressure unloading. Then cardiac contractility modulation was delivered to the myocardium lasting six hours per day for 4 weeks. Histology examination was carried out to evaluate the myocardial pathological changes. Protein levels of collagen I, collagen III, α-SMA, MMP2, MMP9, TIMP1, TGF-β1 and Smad3 were measured by western blot analysis. Results: Histology examination results showed that CCM therapy attenuated myocardial fibrosis and collagen deposition in rabbits with CHF. In addition, protein levels of collagen I, collagen III, α-SMA, MMP2, MMP9, TIMP1, TGF-β1 and Smad3 were down regulated. Conclusion: CCM therapy exerted protective effects against myocardial fibrosis potentially by inhibiting TGF-β1/Smad3 signaling pathway in CHF rabbits.

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