scholarly journals Heart Size Corrected Electrical Dyssynchrony and Its Impact on Sex-specific Response to Cardiac Resynchronization Therapy

2020 ◽  
Author(s):  
Odette A.E. Salden ◽  
Antonius M.W. van Stipdonk ◽  
Hester M. den Ruijter ◽  
Maarten Jan Cramer ◽  
Mariëlle Kloosterman ◽  
...  
Keyword(s):  
Cardiac Resynchronization Therapy ◽  
Left Ventricular ◽  
Cardiac Resynchronization ◽  
Reverse Remodeling ◽  
Specific Response ◽  
Composite Outcome ◽  
Resynchronization Therapy ◽  
Systolic Volume ◽  
Female Sex ◽  
Heart Size

Background - Women are less likely to receive cardiac resynchronization therapy (CRT), yet, they are more responsive to the therapy and respond at shorter QRS duration. The present study hypothesized that a relatively larger left ventricular (LV) electrical dyssynchrony in smaller hearts contributes to the better CRT response in women. For this the vectorcardiography-derived QRS area is used, since it allows for a more detailed quantification of electrical dyssynchrony compared to conventional electrocardiographic markers. Methods - Data from a multicenter registry of 725 CRT patients (median follow-up: 4.2 years [IQR: 2.7-6.1]) were analyzed. Baseline electrical dyssynchrony was evaluated using the QRS area, and the corrected QRS area for heart size using the LV end-diastolic volume (QRSarea/LVEDV). Impact of the QRSarea/LVEDV-ratio on the association between sex and LV reverse remodeling (end-systolic volume change: ΔLVESV) and sex and the composite outcome of all-cause mortality, LV assist device implantation or heart transplantation was assessed. Results - At baseline, women (n=228) displayed larger electrical dyssynchrony than men (QRS area: 132±55μVs vs 123±58μVs, p =0.043) which was, even more pronounced for the QRSarea/LVEDV-ratio (0.76±0.46μVs/ml vs 0.57±0.34μVs/ml, p <0.001). After multivariable analyses female sex was associated with ΔLVESV (β 0.12, p =0.003) and a lower occurrence the composite outcome (HR 0.59 (0.42-0.85), p =0.004). A part of the female advantage regarding reverse remodeling was attributed to the larger QRSarea/LVEDV-ratio in women (25-fold change in Beta from 0.12 to 0.09). The larger QRSarea/LVEDV-ratio did not contribute to the better survival observed in women. In both volumetric responders and non-responders, female sex remained strongly associated with a lower risk of the composite outcome (adjusted HR 0.59 (0.36-0.97), p =0.036 and 0.55 (0.33-0.90), p =0.018, respectively). Conclusions - Greater electrical dyssynchrony in smaller hearts contributes in part to more reverse remodeling observed in women after CRT, but this does not explain their better long-term outcomes.

scholarly journals Improvement of LV Reverse Remodeling Using Dynamic Programming of Fusion-Optimized Atrioventricular Intervals in Cardiac Resynchronization Therapy

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhongkai Wang ◽  
Pan Li ◽  
Bili Zhang ◽  
Jingjuan Huang ◽  
Shaoping Chen ◽  
...  
Keyword(s):  
Cardiac Resynchronization Therapy ◽  
Nyha Class ◽  
Left Ventricular ◽  
Cardiac Resynchronization ◽  
Reverse Remodeling ◽  
Resynchronization Therapy ◽  
Systolic Volume ◽  
End Systolic Volume ◽  
The Impact

Background: The patient-tailored SyncAV algorithm shortens the QRS duration (QRSd) beyond what conventional biventricular (BiV) pacing can. However, evidence of the ability of SyncAV to improve the cardiac resynchronization therapy (CRT) response is lacking. The aim of this study was to evaluate the impact of CRT enhanced by SyncAV on echocardiographic and clinical responses.Methods and Results: Consecutive heart failure (HF) patients from three centers treated with a quadripolar CRT system (Abbott) were enrolled. The total of 122 patients were divided into BiV+SyncAV (n = 68) and BiV groups (n = 54) according to whether they underwent CRT with or without SyncAV. Electrocardiographic, echocardiographic, and clinical data were assessed at baseline and during follow-up. Echocardiographic response to CRT was defined as a ≥15% decrease in left ventricular end-systolic volume (LVESV), and clinical response was defined as a NYHA class reduction of ≥1. At the 6-month follow-up, the baseline QRSd and LVESV decreased more significantly in the BiV+SyncAV than in the BiV group (QRSd −36.25 ± 16.33 vs. −22.72 ± 18.75 ms, P &lt; 0.001; LVESV −54.19 ± 38.87 vs. −25.37 ± 36.48 ml, P &lt; 0.001). Compared to the BiV group, more patients in the BiV+SyncAV group were classified as echocardiographic (82.35 vs. 64.81%; P = 0.036) and clinical responders (83.82 vs. 66.67%; P = 0.033). During follow-up, no deaths due to HF deterioration or severe procedure related complications occurred.Conclusion: Compared to BiV pacing, BiV combined with SyncAV leads to a more significant reduction in QRSd and improves LV remodeling and long-term outcomes in HF patients treated with CRT.

scholarly journals A Simple Predictive Marker in Cardiac Resynchronization Therapy Recipients: Prominent S-Wave in Right Precordial Leads

Medicina ◽  
2021 ◽  
Vol 57 (8) ◽  
pp. 815
Author(s):  
Naoya Kataoka ◽  
Teruhiko Imamura ◽  
Takahisa Koi ◽  
Keisuke Uchida ◽  
Koichiro Kinugawa
Keyword(s):  
Cardiac Resynchronization Therapy ◽  
Wave Amplitude ◽  
Left Ventricular ◽  
Cardiac Resynchronization ◽  
Reverse Remodeling ◽  
Resynchronization Therapy ◽  
S Wave ◽  
Systolic Volume ◽  
The Impact ◽  
R Wave Amplitude

Background and objectives: Current guidelines criteria do not satisfactorily discriminate responders to cardiac resynchronization therapy (CRT). QRS amplitude is an established index to recognize the severity of myocardial disturbance and might be a key to optimal patient selection for CRT. Materials and Methods: (1) Initial R-wave amplitude, (2) S-wave amplitude, and (3) a summation of maximal R- or R′-wave amplitude and S-wave amplitude were measured at baseline. These parameters were averaged according to right (V1 to V3) or left (V4 to V6) precordial leads. The impact of these parameters on response to CRT, which was defined as a decrease in left ventricular end-systolic volume ≥15% at six-month follow-up, was investigated. Results: Among 47 patients (71 years old, 28 men) who received guideline-indicated CRT implantation, 25 (53%) achieved the definition of CRT responder. Among baseline electrocardiogram parameters, only the higher S-wave amplitude in right precordial leads was an independent predictor of CRT responders (odds ratio: 2.181, 95% confidence interval: 1.078–4.414, p = 0.030) at a cutoff of 1.44 mV. The cutoff was independently associated with cumulative incidence of heart failure readmission and appropriate electrical defibrillation following CRT implantation (p < 0.05, respectively). Conclusions: Prominent S-wave in right precordial leads might be a promising index to predict left ventricular reverse remodeling and greater clinical outcomes following CRT implantation.

P536Reverse remodeling after cardiac resynchronization therapy is associated with improvement of contractile asymmetry in the area of left ventricular lead position

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
T Zaremba ◽  
B Tayal ◽  
A M Thogersen ◽  
S Riahi ◽  
P Sogaard
Keyword(s):  
Cardiac Resynchronization Therapy ◽  
Spline Interpolation ◽  
Left Ventricular ◽  
Cardiac Resynchronization ◽  
Reverse Remodeling ◽  
Lead Target ◽  
Target Area ◽  
Resynchronization Therapy ◽  
Lead Position ◽  
Ventricular Lead

Abstract Background One third of patients receiving cardiac resynchronization therapy (CRT) do not respond to the treatment, possibly due to suboptimal lead position and persistent dyssynchronous left ventricular (LV) contraction. Purpose To assess the influence of LV lead position on improvement of contractile asymmetry and its significance for LV reverse remodeling after CRT. Methods Patients with heart failure and left bundle branch block undergoing CRT implantation were studied retrospectively. Assessment of mechanical delay within the LV was assessed using a recently developed index of contractile asymmetry (ICA). ICA was calculated as standard deviation of differences in systolic strain rate in the opposing LV walls derived from curved anatomical M-mode plots. LV was divided into 12 equally sized 30-degree sectors. Spline interpolation was used to estimate ICA in six opposing sector pairs permitting quantification of regional contractile asymmetry in the entire LV. Position of LV lead tip was assessed by thoracic computed tomography (CT). Response to CRT was defined as a reduction of LV end-systolic volume (ESV) ≥15% after 6 months. Results Study population (n= 26) consisted of 65.4% males, 68 ± 10 years, ischemic etiology in 42.3%, LV ejection fraction 24.1 ± 5.8%, QRS duration 171 ± 22 ms. CRT response was present in 18 (69.2%) patients. Pre-implantation ICA in the LV sector containing LV lead was 0.75 ± 0.24 s-1 in responders vs. 0.46 ± 0.16 s-1 in non-responders (p = 0.003). Reduction of ICA in the LV sector with LV lead was directly correlated with reduction of LV ESV after CRT (r = 0.46, p = 0.02) (Figure 1). ICA reduction in the LV sector with LV lead was -0.24 ± 0.28 s-1 in responders and -0.05 ± 0.16 s-1 in non-responders (p = 0.03). Meanwhile, reduction of ICA in the LV sectors located 60 degrees clockwise and 60 degrees counterclockwise away from the LV sector with LV lead (remote LV sectors) did not differ significantly between responders and non-responders: -0.12 ± 0.15 s-1 vs. -0.06 ± 0.1 s-1 (p = 0.28). Likewise, no significant correlation between reduction of ICA in remote LV sectors and LV ESV reduction was observed (p = 0.11). Conclusion Pre-implantation contractile asymmetry in the LV lead target area is associated with a positive response to CRT. Simultaneously, the degree of LV reverse remodeling after CRT seems to correlate with the magnitude of improvement of contractile asymmetry specifically in the region of LV lead location. Abstract Figure 1

Abstract 2819: Identification and Characterization of Super-Responders to Cardiac Resynchronization Therapy: An Echocardiographic Study

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Amira Zaroui ◽  
Patricia Reant ◽  
Erwan Donal ◽  
Aude Mignot ◽  
Pierre Bordachar ◽  
...  
Keyword(s):  
Cardiac Resynchronization Therapy ◽  
Longitudinal Strain ◽  
Global Longitudinal Strain ◽  
Strain Analysis ◽  
Left Ventricular ◽  
Cardiac Resynchronization ◽  
Lv Function ◽  
Resynchronization Therapy ◽  
Systolic Volume ◽  
End Systolic Volume

In some patients, cardiac resynchronization therapy (CRT) has been recently shown to induce a spectacular effect on left ventricular (LV) function and inverted remodeling with nearby normalization of LV contraction. Objectives: To analyze and characterize super-responders (CRTSR) by echocardiography before CRT. 186 patients have been investigated before and 6 months after implantation of a CRT device with conventional indication according to ESC guidelines. Echocardiographies including measurements of LV dimensions, and contraction by 2-dimensional strain, and pressure assessment, mitral valve analysis were performed at baseline and at 6 months in an independent core-center lab. CRTSR were defined as a reduction of end-systolic volume of at least 15% and an ejection fraction (EF)>50% and were compared to normal responder patients (CRTNo, patients with a reduction of end-systolic volume of at least 15% but an EF <50%). 17/186 patients (9.1%) were identified as CRTSR, only 2 with ischemic cardiomyopathy (p<0.01). No difference was observed regarding NYHA status, EKG duration or EF between CRTSR and CRTNo at baseline. CRTSR presented with significant lower end-diastolic and end-systolic diameters (64±9mm vs 73±9mm (p<0.01) and 53±7.4mm vs 63±8.4mm (p<0.01), respectively), and end-diastolic and end-systolic volumes 161±44ml vs 210±76ml (p<0.02) and 123±43ml vs 163±69ml (p<0.01)) as well as a higher LV dP/dt max (714±251mmHg.s −1 vs 527±188 mmHg.s −1 (p<0.05)). Regarding strain analysis, CRTSR had significantly higher longitudinal values than CRTNo (−12.8±3% vs −9±2.6%, p<0.001) whereas no difference was observed for other components (p ns). Global longitudinal strain obtained by ROC curves was identified as the best parameter for predicting CRTSR with a cut-off value of −11% (Se=80%, Spe=87%, AUC=0.89, p<0.002) and was confirmed as an independent predictor by the logistic regression (RR: 21.3, p<0.0001). In a large multicenter study, CRT super-responders (EF>50%) were observed in 9% of the population and were associated with less-depressed LV function as determined by strain analysis. Global longitudinal strain appears to be the best predictor of CRTSR.

scholarly journals Diagnostic value of electrocardiographic markers of left bundle branch block in predicting left ventricular reverse remodeling in patients receiving cardiac resynchronization therapy

2021 ◽  
Vol 26 (9) ◽  
pp. 4500
Author(s):  
L. M. Malishevsky ◽  
V. A. Kuznetsov ◽  
V. V. Todosiychuk ◽  
N. E. Shirokov ◽  
D. S. Lebedev
Keyword(s):  
Mathematical Model ◽  
Cardiac Resynchronization Therapy ◽  
Predictive Value ◽  
Diagnostic Value ◽  
Left Ventricular ◽  
Cardiac Resynchronization ◽  
Reverse Remodeling ◽  
Resynchronization Therapy ◽  
Bundle Branch Block ◽  
T Wave

Aim. To analyze the prognostic value of 18 electrocardiographic (ECG) markers of left bundle branch block (LBBB) in predicting left ventricular (LV) reverse remodeling in patients receiving cardiac resynchronization therapy (CRT).Material and methods. The study included 98 patients. Depending on the presence of reverse remodeling during CRT, defined as a decrease in LV endsystolic volume ≥15%, the patients were divided into two groups: non-responders (n=33) and responders (n=65). We selected and analyzed 18 ECG markers included in 9 LBBB criteria.Results. Among the ECG markers significantly associated with reverse remodeling during CRT, the absence of q wave in leads V5-V6 demonstrated the highest sensitivity (92,31%), a negative predictive value (70,59%) and overall accuracy (73,47%). Normal internal deviation interval of the R wave in leads V1-V3 was also associated with the best sensitivity (92.31%), while QS with a positive T in lead aVR — the best specificity (69,7%). Discordant T wave demonstrated the highest positive predictive value (80,33%). Multivariate analysis revealed following ECG signs independently associated with reverse remodeling during CRT: QRS complex duration (odds ratio (OR)=1,022; 95% confidence interval (CI): 1,001-1,043; p=0,040); absence of q wave in leads V5-V6 (OR=4,076; 95% CI: 1,071-15,51; p=0,039); discordant T wave (OR=4,565; 95% CI: 1,708-12,202; p=0,002). These ECG findings were combined into a mathematical model that demonstrated high predictive power (AUC=0,81 [0,722-0,898], p<0,001). Once the cut-off point was determined, a binary variable was obtained that showed higher sensitivity, negative predictive value, and overall accuracy when compared with the actual LBBB criteria. The 5-year survival rate among patients with a model value above the cut-off point was 84,4%, while in patients with a value below the cut-off point — 50% (Log-rank test, p=0,001). To improve usability of the model, a mobile application was developed.Conclusion. For the first time, the diagnostic value of ECG markers of LBBB were analyzed and a mathematical model with ECG signs was proposed to predict reverse remodeling in patients receiving CRT.

scholarly journals Non-invasive myocardial workiIndices derived from left ventricular pressure-strain loops in predicting the response to cardiac resynchronization therapy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M.R Zhu ◽  
X Shu ◽  
H.Y Chen ◽  
Y.N Wang ◽  
Y.F Cheng ◽  
...  
Keyword(s):  
Cardiac Resynchronization Therapy ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Cardiac Resynchronization ◽  
Resynchronization Therapy ◽  
Systolic Volume ◽  
Non Invasive ◽  
Work Distribution ◽  
Constructive Work ◽  
Crt Response

Abstract Background Non-invasive left ventricular (LV) pressure-strain loops (PSLs) which generated by combining LV longitudinal strain with brachial artery blood pressure, provide a novel method of quantifying global and segmental myocardial work (MW) indices with potential advantages over conventional echocardiographic strain which is load-dependent. The method has been introduced in echocardiographic software recently, making MW calculations more effectively and rapidly. The aim was to evaluate the role of non-invasive MW indices derived from LV PSLs in the prediction of cardiac resynchronization therapy (CRT) response. Methods 106 heart failure (HF) patients scheduled for CRT were included for MW analysis. Global and segmental (septal and lateral at the mid-ventricular level) MW indices were accessed before CRT. Response to CRT was defined as ≥15% reduction in LV end-systolic volume at 6-month follow-up in comparison with baseline value. Results CRT response was observed in 78 (74%) patients. At baseline, global work index (GWI) and global constructive work (GCW) were significant higher in CRT responders than in non-responders (both P&lt;0.05). Besides, responders exhibited a significantly higher Mid Lateral MW and Mid Lateral constructive work (CW) (both P&lt;0.001) but a significantly lower Mid Septal MW and Mid Septal myocardial work efficiency (MWE), as well as a significantly higher Mid Septal wasted work (WW) than non-responders (all P&lt;0.01). Baseline Mid Septal MWE (OR 0.975, 95% CI 0.959–0.990, P=0.002) and Mid Lateral MW (OR 1.003, 95% CI 1.002–1.004, P&lt;0.001) were identified as independent predictors of CRT response in multivariate regression analysis. Mid Septal MWE ≤42% combined with Mid Lateral MW ≥740 mm Hg% predicted CRT response with the optimal sensitivity of 79% and specificity of 82% (AUC = 0.830, P&lt;0.001). Conclusion Mid Septal MWE and Mid Lateral MW can successfully predict response to CRT, and their combination can further improve the prediction accuracy. Assessment of MW indices before CRT could identify the marked misbalance in LV myocardial work distribution and has the potential to be widely used as a reliable complementary tool for guiding patient selection in clinical practice. Funding Acknowledgement Type of funding source: None

scholarly journals Analysis of Risk Factors for Acute Heart Failure in Patients with Dilated Cardiomyopathy and Persistent Severe Functional Mitral Regurgitation Despite Cardiac Resynchronization Therapy

2020 ◽  
pp. 35-39
Author(s):  
R. V. Buriak ◽  
K. V. Rudenko ◽  
O. A. Krykunov
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Mitral Regurgitation ◽  
Cardiac Resynchronization Therapy ◽  
Dilated Cardiomyopathy ◽  
Left Ventricular ◽  
Cardiac Resynchronization ◽  
Functional Mitral Regurgitation ◽  
Reverse Remodeling ◽  
Resynchronization Therapy

Congestive heart failure resulting from non-ischemic dilated cardiomyopathy (DCM) with secondary functional mitral regurgitation (FMR) is associated with poor prognosis. Medical treatment results in a 1-year survival of 52% to 87% and a 5-year survival of 22% to 54%, with highest survivals observed in more recent years, probably reflecting improvements in medical therapy. Non-surgical interventions involve cardiac resynchronization therapy. In addition to medical treatment, cardiac resynchronization therapy (CRT) should be considered in patients with New York Heart Association (NYHA) class II– IV HF, left ventricular ejection fraction (LVEF) =35%, normal sinus rhythm and left bundle branch block with QRS >150 ms. In these patients, CRT can also facilitate left ventricular (LV) reverse remodeling and reduce associated FMR. The aim of this study was to investigate the features of symptomatology and to analyze the risk factors for acute heart failure (AHF) in patients with DCM and persistent severe functional mitral regurgitation despite CRT and optimal guideline-directed medical therapy (GDMT). Materials and methods. After providing informed consent, 144 patients with severe FMR were involved in the study. Concomitant tricuspid valve regurgitation was registered in 142 (98.6%) cases. The median LVEF was 27.0 (23.0-31.6)%. 40 (27.8%) patients had a permanent form of atrial fibrillation, and 24 (16.7%) patients had a first-degree atrioventricular node block. The median NT-proBNP was 2600 (2133-3200) pg/ml, indicating the presence of severe chronic heart failure. Results. The median term after CRT device implantation was 36 (3.5-60) months. A comparative analysis between DCM patients with and without CRT revealed statistically significant differences between clinical characteristics, namely: age (p=0.020), lower heart rate (p=0.004), lower hemoglobin (p=0.017), higher erythrocyte sedimentation rate (ESR) (p=0.000) and more frequent AHF at the hospital stage (p=0.030). The incidence of AHF at the hospital stage was 13.8% in patients with CRT and 3.5% in those without CRT. The calculated odds ratio of AHF was 4.44 (95% confidence interval (CI) 1.039-18.971), and the relative risk of AHF was 3.966 (95% CI 1.054-14.915). Discussion. FMR has been reported to persist in about 20% to 25% of CRT patients and, in an additional 10% to 15%, it may actually worsen after CRT. In this subset of CRT non-responders, reduced reverse remodeling, increased morbidity, and increased mortality have been reported compared with CRT patients in whom FMR was significantly reduced or abolished. Conclusions. The results of our study demonstrate that severe functional mitral regurgitation despite cardiac resynchronization therapy in patients with dilated cardiomyopathy is a significant risk factor for AHF and subsequent hospitalizations for heart failure.

P4531Early and late superresponse to cardiac resynchronization therapy

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
V A Kuznetsov ◽  
T N Enina ◽  
A M Soldatova ◽  
T I Petelina ◽  
N E Shirokov ◽  
...  
Keyword(s):  
Cardiac Resynchronization Therapy ◽  
Left Ventricular ◽  
Cardiac Resynchronization ◽  
Reverse Remodeling ◽  
Resynchronization Therapy ◽  
Tnf Α ◽  
Echocardiographic Parameters ◽  
Group 2 ◽  
Group 1

Abstract Background Superresponders to cardiac resynchronization therapy (CRT) demonstrate significant reverse remodeling, improvement in cardiac function, decrease in inflammatory mediators and markers of cardiac fibrosis. It is not clear if superresponse (SR) can be early or late and if the time of SR to CRT is associated with different degree of biochemical improvement. Aim To assess structural and functional heart parameters, sympathetic activity, levels of biomarkers of myocardial fibrosis, inflammatory and neurohormonal mediators in patients with various time of SR to CRT. Methods The study enrolled 82 superresponders to CRT (decrease in left ventricular end-systolic volume (LVESV) >30%) (mean age 60.4±9.3 years; 80.5% men, 19.5% women; 54.9% with ischemic etiology of heart failure). Patients were divided into two groups: group 1 (n=19) – SR was achieved within 24 months (14.0 [8.0; 21.0] months); group 2 (n=63) - SR was achieved after 24 months (59 [43.0; 84.0] months). Echocardiographic parameters, plasma levels of epinephrine, norepinephrine, NT-proBNP, interleukin (IL) 1β, IL-6, IL-10, tumor necrosis factor alpha (TNF-α), metalloproteinase (MMP) 9, tissue inhibitors of metalloproteinase (TIMP) 1 and 4 were evaluated. Results At baseline there were no differences in demographic, clinical and echocardiographic characteristics between the groups. Levels of epinephrine (1.1 [0.1; 2.2] ng/ml vs 2.1 [0.7; 3.4] ng/ml; p=0.049) and IL-10 (1.8 [1.5; 3.5] pg/ml vs 3.9 [2.7; 5.1] pg/ml; p=0.019) were significantly higher in group 2. Both groups demonstrated significant improvement in echocardiographic parameters. On follow-up left ventricular (LV) end-systolic dimension (p=0.041), LV end-diastolic dimension (p=0.049), LVESV (p=0.014), LV end-diastolic volume (p=0.045) were lower in group 2. In group 1 IL-6 (p=0.047), TNF-α (p=0.047) decreased significantly and there was a tendency for IL-1β (p=0.064) and norepinephrine (p=0.069) levels to increase. In group 2 levels of IL-1β (p<0.001), IL-6 (p=0.030), IL-10 (p=0.003), TNF-α (p<0.001), TIMP-1 (p=0.010) and epinephrine (p=0.024) decreased significantly while MMP-9/TIMP-1 (p=0.023) increased as compared to baseline levels. Additionally there was a tendency for NT-proBNP level to decrease in group 2 (p=0.069). Follow-up level of norepinephrine (7.8 [2.9; 17.2] ng/ml vs 1.1 [0.2; 8.7] ng/ml; p=0.011 was lower and MMP-9/TIMP-4 level was higher (0.058 [0.044; 0.091] vs 0.092 [0.064; 0.111]; p=0.013) in group 2. Diverse trends were observed in IL-10 (0.4 [−0.6; 1.2] pg/ml in group 1 vs −2.3 [−3.4; −0.5] pg/ml in group 2; p=0.007) and norepinephrine (4.0 [−5.2; 14.3] ng/ml in the group 1 vs −1.2 [−11.6; 4.0] ng/ml in the group 2; p=0.015) between the groups. Conclusion CRT modulates sympathetic, neurohumoral, immune and fibrotic activity. Late SR to CRT is associated with decrease of sympathetic and inflammatory activity and more pronounced LV reverse remodeling.

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