scholarly journals Effect of cardiac resynchronization therapy on left ventricular fibrosis-related mRNA expression profile in patients with end-stage heart failure

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A.A Sayour ◽  
A Olah ◽  
M Ruppert ◽  
B.A Barta ◽  
M Polos ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Expression Profile ◽  
Biventricular Pacing ◽  
Left Ventricular ◽  
Cardiac Resynchronization ◽  
Resynchronization Therapy ◽  
Mrna Expression Profile ◽  
Reverse Remodelling ◽  
History Of ◽  
End Stage

Abstract Background When indicated, cardiac resynchronization therapy (biventricular pacing, CRT) decreases mortality in patients with heart failure (HF) and reduced ejection fraction, especially in those with non-ischemic cardiomyopathy. This is reflected by relatively rapid improvement of left ventricular (LV) end-diastolic diameter (LVEDD) and LV ejection fraction (LVEF) indicating reverse remodelling. These LV structural and functional improvements are accompanied by characteristic changes in LV gene expression profile. However, whether beneficial gene expression alterations related to biventricular pacing are sustained independently of structural and functional reverse remodelling is unclear. Purpose We aimed to compare LV fibrosis-related mRNA expression profile in end-stage HF patients with idiopathic dilated cardiomyopathy (DCM) who were not on CRT versus to those on CRT. Methods Left ventricular myocardial samples were harvested from end-stage HF patients undergoing heart transplantation (HTX). Inclusion criteria were negative family history of DCM, negative coronarography (i.e. non-ischemic), no relevant comorbidity (e.g. diabetes, hypertension) and no history of myocarditis. Accordingly, the following patient groups were included: 1.) DCM (n=12, 17% female, mean age [±standard deviation] 46.8±11.8 years) without CRT and 2.) CRT-DCM (n=12, 42% female, mean age 47.8±12.3 years) which comprised DCM patients on active CRT for mean 3.2±2.4 years until HTX. LV RNA was extracted and subjected to a commercially available mRNA expression panel interrogating 760 genes related to the development and regulation of fibrosis. Normalization to 10 housekeeping genes and batch corrections were conducted as per protocol. LV mRNA expression of atrial-natriuretic peptide (ANP) was quantified using qRT-PCR. Results Markers of reverse remodelling including LVEDD (73.4±8.3 mm vs 75.4±9.9 mm), LVEF (21.9±3.7% vs 18.5±6.8%) and LV ANP mRNA expression (arbitrary units: 1.05±1.80 vs 1.04±0.88) were comparable between DCM and CRT-DCM patients (all P>0.05), respectively. High-throughput mRNA expression screening revealed significant (all P<0.001) downregulation of 3 genes proven to be implicated in adverse LV remodelling: alpha catalytic subunit of protein phosphatase 2 (PPP2CA), interleukin 20 receptor subunit beta (IL20RB) and lipoprotein lipase (LPL). According to pathway analysis using directed significance scores, CRT was associated with collective upregulation of genes modifying complement activation (SERPING1, C1S, CFH) and collective downregulation of genes promoting cell proliferation (PPP2CA, ANAPC7, HSP90AA1, CSNK2B). Conclusions Independently of structural and functional reverse remodelling, CRT might be associated with slightly favourable LV expression profile of genes related to the regulation and development of fibrosis. This suggests that biventricular pacing might be beneficial on the molecular level beyond improvement of LV structure and function. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Research, Development and Innovation Fund of Hungary, Higher Education Institutional Excellence Programme of the Ministry of Human Capacities of Hungary

Biventricular pacing-induced acute response in baroreflex sensitivity has predictive value for midterm response to cardiac resynchronization therapy

2009 ◽  
Vol 297 (1) ◽  
pp. H233-H237 ◽  
Author(s):  
Maaike G. J. Gademan ◽  
Rutger J. van Bommel ◽  
C. Jan Willem Borleffs ◽  
SumChe Man ◽  
Joris C. W. Haest ◽  
...  
Keyword(s):  
Cardiac Resynchronization Therapy ◽  
Predictive Value ◽  
Baroreflex Sensitivity ◽  
Biventricular Pacing ◽  
Left Ventricular ◽  
Cardiac Resynchronization ◽  
Arterial Baroreflex ◽  
Resynchronization Therapy ◽  
Acute Response

In a previous study we demonstrated that the institution of biventricular pacing in chronic heart failure (CHF) acutely facilitates the arterial baroreflex. The arterial baroreflex has important prognostic value in CHF. We hypothesized that the acute response in baroreflex sensitivity (BRS) after the institution of cardiac resynchronization therapy (CRT) has predictive value for midterm response. One day after implantation of a CRT device in 33 CHF patients (27 male/6 female; age, 66.5 ± 9.5 yr; left ventricular ejection fraction, 28 ± 7%) we measured noninvasive BRS and heart rate variability (HRV) in two conditions: CRT device switched on and switched off (on/off order randomized). Echocardiography was performed before implantation (baseline) and 6 mo after implantation (follow-up). CRT responders were defined as patients in whom left ventricular end-systolic volume at follow-up had decreased by ≥15%. Responders (69.7%) and nonresponders (30.3%) had similar baseline characteristics. In responders, CRT increased BRS by 30% ( P = 0.03); this differed significantly ( P = 0.02) from the average BRS change (−2%) in the nonresponders. CRT also increased HRV by 30% in responders ( P = 0.02), but there was no significant difference found compared with the increase in HRV (8%) in the nonresponders. Receiver-operating characteristic curve analysis revealed that the percent BRS increase had predictive value for the discrimination of responders and nonresponders (area under the curve, 0.69; 95% confidence interval, 0.51–0.87; maximal accuracy, 0.70). Our study demonstrates that a CRT-induced acute BRS increase has predictive value for the echocardiographic response to CRT. This finding suggests that the autonomic nervous system is actively involved in CRT-related reverse remodeling.

Cardiac resynchronization therapy: optimization and follow-up

2015 ◽  
pp. 420-431
Author(s):  
Marta Sitges ◽  
Genevieve Derumeaux
Keyword(s):  
Cardiac Resynchronization Therapy ◽  
Imaging Techniques ◽  
Biventricular Pacing ◽  
Left Ventricular ◽  
Cardiac Resynchronization ◽  
Functional Mitral Regurgitation ◽  
Cardiac Imaging Techniques ◽  
Resynchronization Therapy

Cardiac imaging techniques have an important role in the follow-up of patients undergoing cardiac resynchronization therapy (CRT) as they provide objective evidence of changes in cardiac dimensions and function. The role of echocardiography is well established in the assessment of left ventricular reverse remodelling and the evaluation of secondary (functional) mitral regurgitation. Additionally, echocardiography might be used for optimizing the programming of atrio-ventricular (AV) and inter-ventricular (VV) delays of current CRT devices. Acute benefits from this optimization have been demonstrated, but longer follow-up studies have failed to show a clear benefit of optimized CRT on top of simultaneous biventricular pacing on the outcome of patients with CRT. This chapter reviews the role of imaging in assessing follow-up and outcome of patients undergoing CRT, as well as the rationale, the methods used, and the clinical impact of optimization of the programming of CRT devices.

45Improving the optimization of cardiac resynchronization therapy: Does multipoint left ventricular pacing shorten the paced-QRS duration compared to the fusion-optimized intervals method?

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
R San Antonio ◽  
M Pujol-Lopez ◽  
R Jimenez-Arjona ◽  
A Doltra ◽  
F Alarcon ◽  
...  
Keyword(s):  
Cardiac Resynchronization Therapy ◽  
Biventricular Pacing ◽  
Left Ventricular ◽  
Cardiac Resynchronization ◽  
Reverse Remodeling ◽  
Prospective Clinical Study ◽  
Battery Life ◽  
Resynchronization Therapy ◽  
Qrs Duration ◽  
Phrenic Stimulation

Abstract Funding Acknowledgements Cardiac Pacing Scholarship from the Spanish Society of Cardiology (SEC) Background Electrocardiogram-based optimization of cardiac resynchronization therapy (CRT) using the fusion-optimized intervals (FOI) method has demonstrated to improve both acute hemodynamic response and left ventricle (LV) reverse remodeling compared to nominal programming of CRT. FOI optimizes the atrioventricular (AV) and ventriculo-ventricular (VV) intervals to achieve the shortest paced-QRS duration. The recent development of multipoint pacing (MPP) enables the activation of the LV from 2 locations, also shortening the QRS duration compared to conventional biventricular pacing. Purpose To determine if MPP reduces the paced-QRS duration compared to FOI optimization.  Methods This prospective clinical study included 25 consecutive patients who successfully received a CRT with MPP pacing capability. All patients were in sinus rhythm and had an PR interval below 250 ms. The QRS duration was measured with a 12-lead digital electrocardiography (screen speed of 200 mm/s) at baseline and using 3 different configurations: MPP, FOI and a combined FOI-MPP strategy. In MPP, the intervals were (based on previous studies): 1) AV 130 ms, 2) Right ventricular (RV)-LV2 (Δ1) 5 ms, and 3) LV1-LV2 (Δ2) 5 ms. In FOI, AV and VV intervals were optimized to achieve fusion between intrinsic conduction and biventricular pacing. In FOI-MPP, the Δ2 was set at 5 ms, while AV and Δ1 intervals were optimized using the FOI method. The CRT device was programmed with the configuration that achieved a greater paced-QRS shortening. After 45 days, battery life was estimated. Results   Mean age was 65 ± 10 years, 20 were men (80%) and baseline QRS duration was 177 ± 17 ms. The FOI method bested nominal MPP (QRS shortened by 58 ± 16 ms vs 43 ± 16 ms, respectively, p = 0.002). Adding MPP to the narrowest QRS by FOI did not result in further shortening (FOI: 58 ± 16 ms vs FOI-MPP: 59 ± 13 ms, p = 0.81). The final configuration was FOI method alone in most cases (n = 16, 64%) and FOI-MPP in all others (n = 9, 36%; figure). In total, 10 out of 25 patients (40%) were not candidates to MPP due to: 1) pacing thresholds exceeding 3.5 V/0.4 ms at the distal or proximal electrode (8, 32%), and 2) phrenic stimulation (2, 8%). Estimated battery longevity was longer in patients receiving FOI as compared to MPP (8.3 ± 2.1 years vs. 6.2 ± 2.2 years, p = 0.04). Conclusion In CRT, the FOI method is not improved by coupling with MPP.  Up to 40% of patients are not candidates for MPP due to high thresholds or phrenic stimulation. The use of MPP in unselected patients would result in a decrease of battery longevity, without any additional benefit over FOI. Abstract Figure.

scholarly journals Septal contraction predicts acute haemodynamic improvement and paced QRS width reduction in cardiac resynchronization therapy

2020 ◽  
Vol 21 (8) ◽  
pp. 845-852 ◽  
Author(s):  
Stian Ross ◽  
Eirik Nestaas ◽  
Erik Kongsgaard ◽  
Hans H Odland ◽  
Trine F Haland ◽  
...  
Keyword(s):  
Cardiac Resynchronization Therapy ◽  
Diastolic Pressure ◽  
Electrical Response ◽  
Electrical Parameter ◽  
Biventricular Pacing ◽  
Left Ventricular ◽  
Cardiac Resynchronization ◽  
Resynchronization Therapy ◽  
Device Implantation ◽  
Crt Response

Abstract Aims  Three distinct septal contraction patterns typical for left bundle branch block may be assessed using echocardiography in heart failure patients scheduled for cardiac resynchronization therapy (CRT). The aim of this study was to explore the association between these septal contraction patterns and the acute haemodynamic and electrical response to biventricular pacing (BIVP) in patients undergoing CRT implantation. Methods and results  Thirty-eight CRT candidates underwent speckle tracking echocardiography prior to device implantation. The patients were divided into two groups based on whether their septal contraction pattern was indicative of dyssynchrony (premature septal contraction followed by various amount of stretch) or not (normally timed septal contraction with minimal stretch). CRT implantation was performed under invasive left ventricular (LV) pressure monitoring and we defined acute CRT response as ≥10% increase in LV dP/dtmax. End-diastolic pressure (EDP) and QRS width served as a diastolic and electrical parameter, respectively. LV dP/dtmax improved under BIVP (737 ± 177 mmHg/s vs. 838 ± 199 mmHg/s, P < 0.001) and 26 patients (68%) were defined as acute CRT responders. Patients with premature septal contraction (n = 27) experienced acute improvement in systolic (ΔdP/dtmax: 18.3 ± 8.9%, P < 0.001), diastolic (ΔEDP: −30.6 ± 29.9%, P < 0.001) and electrical (ΔQRS width: −23.3 ± 13.2%, P < 0.001) parameters. No improvement under BIVP was observed in patients (n = 11) with normally timed septal contraction (ΔdP/dtmax: 4.0 ± 7.8%, P = 0.12; ΔEDP: −8.8 ± 38.4%, P = 0.47 and ΔQRS width: −0.9 ± 11.4%, P = 0.79). Conclusion  Septal contraction patterns are an excellent predictor of acute CRT response. Only patients with premature septal contraction experienced acute systolic, diastolic, and electrical improvement under BIVP.

Plasma osteopontin reveals left ventricular reverse remodelling following cardiac resynchronization therapy in heart failure

2011 ◽  
Vol 153 (3) ◽  
pp. 306-310 ◽  
Author(s):  
Pietro Francia ◽  
Cristina Balla ◽  
Agnese Ricotta ◽  
Arianna Uccellini ◽  
Alessandra Frattari ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Resynchronization Therapy ◽  
Left Ventricular ◽  
Cardiac Resynchronization ◽  
Resynchronization Therapy ◽  
Reverse Remodelling

scholarly journals Cardiac Resynchronization Therapy using Left-Bundle-Branch Area and Left Ventricular Pacing

2020 ◽  
Author(s):  
Xiang-Fei Feng ◽  
Ling-Chao Yang ◽  
Rui Zhang ◽  
Yi Yu ◽  
Bo Liu ◽  
...  
Keyword(s):  
New York ◽  
Cardiac Resynchronization Therapy ◽  
Biventricular Pacing ◽  
Operation Time ◽  
Heart Association ◽  
Left Ventricular ◽  
Functional Class ◽  
Cardiac Resynchronization ◽  
Lv Function ◽  
Resynchronization Therapy

Introduction: Cardiac resynchronization therapy via biventricular pacing is an established therapy for patients with heart failure. However, high nonresponder rates and inability to predict response remains a challenge. Recently left bundle branch area pacing (LBBAP) has been shown to be feasible and may also improve clinical outcomes. In this article we describe sequential LBBAP followed by left ventricular (LV) pacing (LOT-CRT) and assess the feasibility of LOT-CRT. Methods: The RV implantation site was positioned and the LBBAP lead was implanted using our methods. The QRS duration (QRSd) at baseline, during LBBAP, biventricular pacing, and LOT-CRT was measured. Results: LOT-CRT was successful in 5 patients (age 71.8 ± 5.1 years, men 3, ischemic 3). The QRSd at baseline was 158.0 ± 13.0 ms and significantly narrowed to 117.0 ± 6.7 ms during LOT-CRT (P < 0.01). During 3-month follow-up, LV ejection fraction improved from 32.8 ± 5.2 % to 45.0 ± 5.1% (P < 0.01), and New York Heart Association functional class changed from 3.25 ± 0.5 to 2.5 ± 0.6 (P < 0.05). A decrease in left ventricular end-diastolic dimension was observed, with widening from (68.2 ± 12.3) mm at baseline to (62.2 ± 11.3) mm at pacing (P < 0.05). The length of operation time was (152.0 ± 31.1) min. Conclusions: The study demonstrates that LOT-CRT is clinically feasible in patients with systolic HF and LBBB. LOT-CRT was associated with significant narrowing of QRSd and improvement in LV function, especially in patients with ischemic cardiomyopathy.

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