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Finding New Insights in Cardiac Resynchronization Therapy and the Pathophysiology...
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Finding New Insights in Cardiac Resynchronization Therapy and the Pathophysiology behind Left Ventricular Dyssynchrony

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Cardiology".

Deadline for manuscript submissions: closed (23 December 2023) | Viewed by 4696

Special Issue Editor

Dr. Jürgen Duchenne

E-Mail Website
Guest Editor
1. Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium
2. Department of Cardiovascular Diseases, University Hospitals Leuven, Leuven, Belgium
Interests: cardiac resynchronization therapy; dyssynchrony; cardiac pathophysiology; cardiac remodeling; heart failure

Special Issue Information

Dear colleagues,

Selecting patients for Cardiac Resynchronization Therapy (CRT) remains a topic of controversy. The beneficial effect of CRT in heart failure patients with a reduced left ventricular ejection fraction (LVEF ≤ 35%) and a left bundle branch block (LBBB) with a QRS width of more than 150ms is often regarded as undisputable (Class I indication). However, long term follow-up of patients receiving CRT has consistently shown a wide range of response, even in Class I patients.

Patients that fall outside of Class I criteria (e.g., LVEF 35-45%) also repeatedly show a response to CRT. Such observations suggest the need for better patient phenotyping beyond QRS width and LV function. The presence of LV dyssynchrony on imaging has received much attention after being unveiled as a key substrate, curable by CRT.

Further research into the underlying pathophysiology may identify other important selection markers and may open up the current guideline criteria. Together with continued technological developments, hope exists to optimize the use of resynchronization therapy and to deliver this technique to all patients that could benefit.

In this Special Issue in the Journal of Clinical Medicine—dedicated to patient phenotyping for CRT and CRT in general—we welcome original research and review articles that: (1) shed new light on the pathophysiology; (2) highlight and provide answers to unmet clinical needs; (3) provide insights that could expand or improve guideline indications; and (4) discuss future directions in research. Manuscripts with both a clinical and a translational focus (large animal research/applied computer models/machine learning/…) will be considered.

Dr. Jürgen Duchenne
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cardiac resynchronization therapy
  • dyssynchrony
  • pathophysiology
  • remodelling
  • response

Published Papers (4 papers)

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Editorial

Jump to: Research, Review

3 pages, 179 KiB  
Editorial
Finding New Insights in Cardiac Resynchronization Therapy and the Pathophysiology behind Left Ventricular Dyssynchrony
by Jürgen Duchenne
J. Clin. Med. 2022, 11(22), 6831; https://doi.org/10.3390/jcm11226831 - 18 Nov 2022
Viewed by 782
Abstract
Over the past two decades, cardiac resynchronization therapy (CRT) became an established treatment option for patients with symptomatic heart failure [...] Full article
(This article belongs to the Special Issue Finding New Insights in Cardiac Resynchronization Therapy and the Pathophysiology behind Left Ventricular Dyssynchrony)

Research

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15 pages, 1630 KiB  
Article
Mechanical Dyssynchrony Combined with Septal Scarring Reliably Identifies Responders to Cardiac Resynchronization Therapy
by Jürgen Duchenne, Camilla K. Larsen, Marta Cvijic, Elena Galli, John M. Aalen, Boudewijn Klop, Oana Mirea, Alexis Puvrez, Stéphanie Bézy, Laurine Wouters, Lennert Minten, Per A. Sirnes, Faraz H. Khan, Gabor Voros, Rik Willems, Martin Penicka, Erik Kongsgård, Einar Hopp, Jan Bogaert, Otto A. Smiseth, Erwan Donal and Jens-Uwe Voigtadd Show full author list remove Hide full author list
J. Clin. Med. 2023, 12(18), 6108; https://doi.org/10.3390/jcm12186108 - 21 Sep 2023
Cited by 1 | Viewed by 919
Abstract
Background and aim: The presence of mechanical dyssynchrony on echocardiography is associated with reverse remodelling and decreased mortality after cardiac resynchronization therapy (CRT). Contrarily, myocardial scar reduces the effect of CRT. This study investigated how well a combined assessment of different markers of [...] Read more.
Background and aim: The presence of mechanical dyssynchrony on echocardiography is associated with reverse remodelling and decreased mortality after cardiac resynchronization therapy (CRT). Contrarily, myocardial scar reduces the effect of CRT. This study investigated how well a combined assessment of different markers of mechanical dyssynchrony and scarring identifies CRT responders. Methods: In a prospective multicentre study of 170 CRT recipients, septal flash (SF), apical rocking (ApRock), systolic stretch index (SSI), and lateral-to-septal (LW-S) work differences were assessed using echocardiography. Myocardial scarring was quantified using cardiac magnetic resonance imaging (CMR) or excluded based on a coronary angiogram and clinical history. The primary endpoint was a CRT response, defined as a ≥15% reduction in LV end-systolic volume 12 months after implantation. The secondary endpoint was time-to-death. Results: The combined assessment of mechanical dyssynchrony and septal scarring showed AUCs ranging between 0.81 (95%CI: 0.74–0.88) and 0.86 (95%CI: 0.79–0.91) for predicting a CRT response, without significant differences between the markers, but significantly higher than mechanical dyssynchrony alone. QRS morphology, QRS duration, and LV ejection fraction were not superior in their prediction. Predictive power was similar in the subgroups of patients with ischemic cardiomyopathy. The combined assessments significantly predicted all-cause mortality at 44 ± 13 months after CRT with a hazard ratio ranging from 0.28 (95%CI: 0.12–0.67) to 0.20 (95%CI: 0.08–0.49). Conclusions: The combined assessment of mechanical dyssynchrony and septal scarring identified CRT responders with high predictive power. Both visual and quantitative markers were highly feasible and demonstrated similar results. This work demonstrates the value of imaging LV mechanics and scarring in CRT candidates, which can already be achieved in a clinical routine. Full article
(This article belongs to the Special Issue Finding New Insights in Cardiac Resynchronization Therapy and the Pathophysiology behind Left Ventricular Dyssynchrony)
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Graphical abstract

12 pages, 1769 KiB  
Article
Impact of Estimated Left Atrial Pressure on Cardiac Resynchronization Therapy Outcome
by Ahmed S. Beela, Claudia A. Manetti, Aurore Lyon, Frits W. Prinzen, Tammo Delhaas, Lieven Herbots and Joost Lumens
J. Clin. Med. 2023, 12(15), 4908; https://doi.org/10.3390/jcm12154908 - 26 Jul 2023
Viewed by 782
Abstract
Background: We investigated the impact of baseline left atrial (LA) strain data and estimated left atrial pressure (LAP) by applying the 2016 American Society of Echocardiography and the European Association of Cardiovascular Imaging (ASE/EACVI) guidelines on cardiac resynchronization therapy (CRT) outcomes. Methods: Datasets [...] Read more.
Background: We investigated the impact of baseline left atrial (LA) strain data and estimated left atrial pressure (LAP) by applying the 2016 American Society of Echocardiography and the European Association of Cardiovascular Imaging (ASE/EACVI) guidelines on cardiac resynchronization therapy (CRT) outcomes. Methods: Datasets of 219 CRT patients were retrospectively analysed. All patients had full echocardiographic diastolic function assessment before CRT and were classified based on the guideline algorithm into normal LAP (nLAP = 40%), elevated LAP (eLAP = 49%) and indeterminate LAP (iLAP = 11%). All relevant baseline characteristics were analysed. CRT-induced left ventricular (LV) reverse remodeling was measured as the relative change of LV end-systolic volume (LVESV) at 12 ± 6 months after CRT compared to baseline. Patients were followed up for all-cause mortality for a mean of 4.8 years [interquartile range (IQR): 2.7–6.0 years]. Results: At follow-up, CRT resulted in more pronounced reduction of LVESV in patients with nLAP than in patients with eLAP. In univariate analysis, nLAP was associated with LV reverse remodelling (p < 0.001), as well as long-term survival after CRT (p < 0.01). However, multivariable analysis showed that only the association between nLAP and LV reverse remodelling after CRT is independent (p < 0.01). Adding LA strain analysis to the guideline algorithm improved the feasibility of LAP estimation without affecting the association between estimated LAP and CRT outcome. Conclusion: Normal LAP before CRT, estimated using the 2016 ASE/EACVI guideline algorithm, is associated with LV reverse remodelling and long-term survival after CRT. Albeit non-independent, it can serve as a non-invasive imaging-based predictor of effective therapy. Furthermore, the inclusion of LA reservoir strain in the guideline algorithm can enhance the feasibility of LAP estimation without affecting the association between LAP and CRT outcome. Full article
(This article belongs to the Special Issue Finding New Insights in Cardiac Resynchronization Therapy and the Pathophysiology behind Left Ventricular Dyssynchrony)
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Review

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11 pages, 1018 KiB  
Review
Plasma Extracellular Vesicles as Liquid Biopsy to Unravel the Molecular Mechanisms of Cardiac Reverse Remodeling Following Resynchronization Therapy?
by Frans A. van Nieuwenhoven, Blanche Schroen, Lucio Barile, Lars van Middendorp, Frits W. Prinzen and Angelo Auricchio
J. Clin. Med. 2023, 12(2), 665; https://doi.org/10.3390/jcm12020665 - 13 Jan 2023
Viewed by 1381
Abstract
Cardiac resynchronization therapy (CRT) has become a valuable addition to the treatment options for heart failure, in particular for patients with disturbances in electrical conduction that lead to regionally different contraction patterns (dyssynchrony). Dyssynchronous hearts show extensive molecular and cellular remodeling, which has [...] Read more.
Cardiac resynchronization therapy (CRT) has become a valuable addition to the treatment options for heart failure, in particular for patients with disturbances in electrical conduction that lead to regionally different contraction patterns (dyssynchrony). Dyssynchronous hearts show extensive molecular and cellular remodeling, which has primarily been investigated in experimental animals. Evidence showing that at least several miRNAs play a role in this remodeling is increasing. A comparison of results from measurements in plasma and myocardial tissue suggests that plasma levels of miRNAs may reflect the expression of these miRNAs in the heart. Because many miRNAs released in the plasma are included in extracellular vesicles (EVs), which protect them from degradation, measurement of myocardium-derived miRNAs in peripheral blood EVs may open new avenues to investigate and monitor (reverse) remodeling in dyssynchronous and resynchronized hearts of patients. Full article
(This article belongs to the Special Issue Finding New Insights in Cardiac Resynchronization Therapy and the Pathophysiology behind Left Ventricular Dyssynchrony)
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