scholarly journals The Relationship of Myocardial Collagen Metabolism and Reverse Remodeling after Cardiac Resynchronization Therapy

2016 ◽  
Vol 35 (2) ◽  
pp. 130-136 ◽  
Author(s):  
Ivana Petrovic ◽  
Ivan Stankovic ◽  
Goran Milasinovic ◽  
Gabrijela Nikcevic ◽  
Bratislav Kircanski ◽  
...  
Keyword(s):  
Heart Failure ◽  
Collagen Synthesis ◽  
Left Ventricular ◽  
Cardiac Resynchronization ◽  
Reverse Remodeling ◽  
Resynchronization Therapy ◽  
Relationship Of ◽  
The Relationship ◽  
Myocardial Collagen

SummaryBackground:In the majority of patients with a wide QRS complex and heart failure resistant to optimal medical therapy, cardiac resynchronization therapy (CRT) leads to rever se ventricular remodeling and possibly to changes in cardiac collagen synthesis and degradation. We investigated the relationship of biomarkers of myocardial collagen meta bolism and volumetric response to CRT.Methods:We prospectively studied 46 heart failure patients (mean age 61±9 years, 87% male) who underwent CRT im plantation. Plasma concentrations of amino-terminal pro peptide type I (PINP), a marker of collagen synthesis, and carboxy-terminal collagen telopeptide (CITP), a marker of collagen degradation, were measured before and 6 months after CRT. Response to CRT was defined as 15% or greater reduction in left ventricular end-systolic volume at 6-month follow-up.Results:Baseline PINP levels showed a negative correlation with both left ventricular end-diastolic volume (r=−0.51; p=0.032), and end-systolic diameter (r=−0.47; p=0.049). After 6 months of device implantation, 28 patients (61%) responded to CRT. No significant differences in the base-line levels of PINP and CITP between responders and nonresponders were observed (p>0.05 for both). During follow-up, responders demonstrated a significant increase in serum PINP level from 31.37±18.40 to 39.2±19.19 μg/L (p=0.049), whereas in non-responders serum PINP levels did not significantly change (from 28.12±21.55 to 34.47±18.64 μg/L; p=0.125). There were no significant changes in CITP levels in both responders and non-responders (p>0.05).Conclusions:Left ventricular reverse remodeling induced by CRT is associated with an increased collagen synthesis in the first 6 months of CRT implantation.

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.

Abstract 1604: Response to Cardiac Resynchronization Therapy Differs Between Patients With and Without Previous Right Ventricular Pacing

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Andrea M Thelen ◽  
Christopher L Kaufman ◽  
Kevin V Burns ◽  
Daniel R Kaiser ◽  
Aaron S Kelly ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Resynchronization Therapy ◽  
Systolic Function ◽  
Radial Strain ◽  
Left Ventricular ◽  
Doppler Imaging ◽  
Cardiac Resynchronization ◽  
Resynchronization Therapy ◽  
Peak Displacement

Background: Previous large studies on the effects of cardiac resynchronization therapy (CRT) in patients with heart failure have generally excluded patients previously paced from the right ventricle (RV). Previously RV paced patients (RVp) can exhibit an iatrogenic cause of dyssynchrony and reduced systolic function and thus, may respond differently to CRT than patients not previously RV paced (nRVp). The purpose of this study was to test the hypothesis that RVp patients have greater improvements in left ventricular systolic function, volumes, and dyssynchrony in response to CRT than nRVp. Methods: Standard echocardiograms with tissue Doppler imaging were performed before and after chronic CRT in RVp (n = 21, 16 male) and nRVp (n = 70, 54 male) heart failure patients. Ejection fraction (EF), left ventricular end diastolic (LVEDV) and systolic (LVESV) volumes were calculated using the biplane Simpson’s method. Longitudinal dyssynchrony was calculated as the standard deviation of time to peak displacement (TT-12) of 12 segments in the apical views. Using mid-ventricular short axis views and speckle-tracking methods, radial dyssynchrony (Rad dys ) was calculated as the maximal time difference between six myocardial segments for peak radial strain. Echo response was defined as ≥ 15% reduction in LVESV. Results are reported as mean ± SD. Results: Significant baseline differences (p < 0.05) were observed between groups (RVp vs. nRVp) for age (74 ± 13 vs. 67 ± 13 year), follow-up time (6.1 ± 1.8 vs. 4.6 ± 2.1 months), LVEDV (154.3±50.8 vs.185.3±56.9 mL), and a trend for LVESV (112.4 ± 40.6 vs. 134.9 ± 47 mL, p = 0 .05). No differences were observed for EF, etiology of heart failure, and dyssynchrony measures between groups at baseline. Echo response rate was significantly ( p < 0.05) greater in RVp (76%) than nRVp (57%). After adjusting for baseline differences, RVp had greater improvement in EF (14 ± 9 vs. 8 ± 7%, p < 0.05) and LVESV (−33 ± 18 vs. −20 ± 21%, p < 0.05). After adjustment for follow-up time, no difference was observed for change in dyssynchrony between groups. Conclusion: RVp patients upgraded to CRT exhibit greater improvements in systolic function and ventricular remodeling as compared to nRVp patients.

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.

P5680One-year outcomes of heart failure patients undergoing cardiac resynchronization therapy using adaptivCRT algorithm

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Briongos Figuero ◽  
A Estevez ◽  
M L Perez ◽  
J B Martinez-Ferrer ◽  
L Alvarez-Costa ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Resynchronization Therapy ◽  
Real Life ◽  
Left Ventricular ◽  
Cardiac Resynchronization ◽  
Ventricular Pacing ◽  
Class Iii ◽  
Resynchronization Therapy ◽  
Risk Of Death

Abstract Background Adaptive cardiac resynchronization therapy (aCRT) algorithm provides synchronized left ventricular (LV) only pacing and ambulatory optimization of the intrinsic atrioventricular and interventricular conduction intervals. Studies reporting morbidity and mortality outcomes of aCRT carriers in daily clinical practice are lacking. Purpose To determine in a real-life setting, whether 1-year outcomes were different among CRT carriers undergoing aCRT pacing and those under conventional biventricular (biV) pacing. Methods Symptomatic heart failure (HF) patients with sinus rhythm undergoing first CRT-defibrillator implant were selected from the UMBRELLA nationwide registry (2012–2017). The primary endpoint was the composite of all-cause mortality or HF hospitalization at 12-month follow-up. HF admission was defined as hospitalization due to symptoms requiring intravenous diuretic treatment. Primary healthcare records were used to prospectively collect all data. Results Two hundred and six patients were collected (66.1±8.7 years; 73.3% male). Eighty-seven out of 206 patients were implanted with an aCRT capable device, but this algorithm was activated at implant and remained enabled at 1-year in 59 patients (aCRT group). The other 147 patients composed the non-aCRT group. At implant left bundle branch block was present in 93% of patients, 69.6% of population was in functional class III or IV and mean left ventricle ejection fraction was of 26.5±5.6%. Non-ischemic cardiomyopathy was present in 63.1% of patients and optimal medical treatment was achieved in majority of population (92% of patients with beta-blockers; angiotensin-converting enzyme inhibitorsor angiotensin II receptor blockersin 89%). The percentage of ventricular pacing through 12 months was 96.1±9.4% in non-aCRT patients and 97.5±2.7% in aCRT patients (p=0.261). In aCRT patients, LV-only pacing accounted for a mean of 53.3±37.6% of all ventricular pacing. After 12-month follow-up period, 25 patients (12.1%) met the primary composite endpoint of death or HF hospitalization. Nine patients died and nineteen patients were admitted due to worsening HF. There was no difference in the risk of all-cause death or HF hospitalization between aCRT and non-aCRT patients (10.2% vs. 12.9% respectively; OR=0.76, CI: 0.29–2.01, p=0.585) Conclusions In this contemporary cohort of HF patients undergoing CRT with high percentages of ventricular pacing, clinical performance of aCRT algorithm was adequate. The risk of death or HF hospitalization was low and no differences were observed at one-year follow-up. Future randomized studies will clarify the role of this algorithm in CRT carriers. Acknowledgement/Funding None

Abstract 3078: Myocardial Collagen Metabolism In Failing Hearts Before And During Cardiac Resynchronization Therapy

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Soban Umar ◽  
Jeroen J Bax ◽  
Margreet Klok ◽  
Marleen H Hessel ◽  
Brigit den Adel ◽  
...  
Keyword(s):  
Cardiac Resynchronization Therapy ◽  
Collagen Synthesis ◽  
Left Ventricular ◽  
Collagen Metabolism ◽  
Cardiac Resynchronization ◽  
Left Ventricular Ejection ◽  
Type I ◽  
Resynchronization Therapy ◽  
Ventricular Ejection Fraction ◽  
Myocardial Collagen

Objective Cardiac resynchronization therapy (CRT) has proven efficacy in improving left ventricular ejection fraction (LVEF), LV diastolic function, NYHA functional class and outcome in patients with congestive heart failure (CHF), although a substantial number of patients respond poorly to CRT. We investigated whether myocardial collagen metabolism of patients with CHF is implicated in good or poor response to CRT. Methods We analyzed collagen synthesis and degradation by measuring the concentrations of aminoterminal propeptides of type I and type III collagen (PINP and PIIINP, resp.) and carboxyterminal telopeptide of type I collagen (ICTP), respectively, in serum of 64 patients with CHF before and 6 months after start of CRT. Patients had NYHA class III–IV, LVEF ≤35%, and QRS duration >120 ms. Results In 46 patients, CRT resulted in >10% reduction of LV end-systolic volume (LVESV), referred to as responders, whereas in 18 patients LVESV did not change upon CRT or even increased, referred to as non-responders. Responders demonstrated an increase of serum PINP and PIIINP upon CRT, from 32.9±2.2 to 46.7±4.0 μg/L (p<0.001) and from 4.59±0.24 to 5.13±0.36 μg/L (p<0.05), respectively, whereas serum PINP and PIIINP of non-responders did not change upon CRT (from 41.8±4.3 to 43.8±6.2 μg/L and from 4.03±0.45 to 4.28±0.31 μg/L, resp.). Responders had higher serum levels of ICTP at baseline and at 6 months follow-up (from 3.38±0.54 to 3.12±0.48 μg/L) than non-responders at both time points (from 1.96±0.37 to 1.92±0.38 μg/L), although these differences were not statistically significant. Conclusion Compared to future non-responders to CRT, future responders demonstrate relatively low levels of markers of collagen synthesis and relatively high levels of markers of collagen degradation at baseline. Unlike non-responders, responders show an increase in collagen synthesis in the first 6 months of CRT.

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