Mitral regurgitation severity at left ventricular assist device implantation is associated with distinct myocardial transcriptomic signatures

Duggal, Neal; Lei, Ienglam; Wu, Xiaoting; Aaronson, Keith D.; Pagani, Francis D.; Lam, Hugo Y. K.; Tang, Paul C.; Haft, Jonathan W.; Romano, Matthew A.; Bolling, Steven F.; Ela, Ashraf Abou El; Janda, Allison M.; Ailawadi, Gorav; Nordsletten, David

doi:10.1016/j.jtcvs.2021.08.061

Cited by 5 publications

(5 citation statements)

References 62 publications

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“…Of these, 340 relevant articles were read in full and assessed according to our inclusion and exclusion criteria. Following critical appraisal, a total of 19 studies [7][8][9][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] incorporating a total of 11 873 patients were included. The studies described outcomes of patients undergoing LVAD implantation with either MR grade 0-I (8819 patients) or II-III (3096 patients).…”

Section: Description Of Studiesmentioning

confidence: 99%

Prognostic value of mitral regurgitation in patients undergoing left ventricular assist device deployment: A systematic review and meta‐analysis

et al. 2023

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BackgroundLeft ventricular assist devices (LVADs) represent an important therapeutic option for patients progressing to end‐stage heart failure. LVAD has previously been shown to have a promising role in improving mitral regurgitation (MR). Nevertheless, the prognostic value of preoperative uncorrected MR in this population remains unclear.MethodsA systematic database search with meta‐analysis was conducted of comparative original articles of patients with preoperative mild MR (Grade 0–I) versus moderate–severe MR (Grade II–III) undergoing LVAD implantation, in EMBASE, MEDLINE, Cochrane database, and Google Scholar, from inception to June 2022. Primary outcomes were overall and operative mortality. Secondary outcomes were neurological dysfunction, gastrointestinal bleeding, right heart failure, LVAD thrombosis, and driveline infection.ResultsOur search yielded 2228 relevant studies. A total of 19 studies met the inclusion criteria with a total of 11 873 patients. LVAD caused a statistically significant decrease of 35.9% in the number of patients with moderate–severe MR (grade II–III) postoperatively. No significant difference was observed in terms of overall mortality, operative mortality, GI bleeding, LVAD thrombosis, and driveline infection rates between mild and moderate–severe MR. An increased rate of right heart failure was seen among patients with moderate–severe MR, while lower rates of neurological events were also observed.ConclusionLVAD improves the haemodynamics of the left ventricle, to promote resolution of MR. Nevertheless, the severity of preoperative mitral regurgitation in patients undergoing LVAD deployment does not seem to affect mortality.

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Section: Description Of Studiesmentioning

confidence: 99%

Prognostic value of mitral regurgitation in patients undergoing left ventricular assist device deployment: A systematic review and meta‐analysis

et al. 2023

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“…While quantification of MR mainly focuses on hemodynamic parameters and imaging, myocardial biology is expected to have an important impact on MR improvement and myocardial recovery. End stage heart failure itself is well known to demonstrate elevated myocardial inflammatory responses (e.g., innate and adaptive immunity, complement activation) coupled with reduced expression of contractile and energetic/oxidative related proteins ( 91 , 92 ). We previously reported that increased MR severity is associated with increasing myocardial immune transcriptomic responses (e.g., complement and innate/adaptive immune responses) in patients undergoing LVAD implantation.…”

Section: Transcriptomic Biology Of Mitral Regurgitation In End-stage ...mentioning

confidence: 99%

“…We previously reported that increased MR severity is associated with increasing myocardial immune transcriptomic responses (e.g., complement and innate/adaptive immune responses) in patients undergoing LVAD implantation. MR is also associated with decreased expression of transcripts related to structural and proliferative pathways ( Figure 3 ; 91 ). Consistent with these biological findings, cardiac imaging in patients with degenerative MR show greater myocardial fluorine 18-lebeled fluorodeoxyglucose uptake which reflect increased myocardial inflammation ( 93 ).…”

Section: Transcriptomic Biology Of Mitral Regurgitation In End-stage ...mentioning

confidence: 99%

“…Published prediction models for LVAD outcomes such as right heart failure and myocardial recovery mainly utilized clinical parameters, imaging, and hemodynamics ( 28 , 29 ), but not specific biological markers. We previously showed that patients with pre-LVAD moderate-severe MR expressing more myocardial inflammatory transcripts are more likely to resolve their MR ( 91 ). Conversely, reduced myocardial inflammation in patients with pre-LVAD moderate-severe MR may indicate a “burnt-out” phenotype with a non-viable and non-contractile LV wall with reduced compliance.…”

Section: Transcriptomic Biology Of Mitral Regurgitation In End-stage ...mentioning

confidence: 99%

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Role of the mitral valve in left ventricular assist device pathophysiology

Noly

Duggal²,

Jiang³

et al. 2022

Front. Cardiovasc. Med.

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Functional mitral regurgitation (MR) in the setting of heart failure results from progressive dilatation of the left ventricle (LV) and mitral annulus. This leads to leaflet tethering with posterior displacement. Contrary to common assumptions, MR often does not resolve with LVAD decompression of the LV alone. The negative impact of significant (moderate-severe) mitral regurgitation in the LVAD setting is becoming better recognized in terms of its harmful effect on right heart function, pulmonary vascular resistance and hospital readmissions. However, controversies remain regarding the threshold for intervention and management. At present, there are no consensus indications for the repair of significant mitral regurgitation at the time of LVAD implantation due to the conflicting data regarding potential adverse effects of MR on clinical outcomes. In this review, we summarize the current understanding of MR pathophysiology in patients supported with LVAD and potential future management strategies.

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“…MR may be secondary to other conditions, such as rheumatic heart disease or congenital abnormalities, and may be the primary cause of heart failure, or exacerbate cardiac insufficiency in a patient with co-existing heart failure. Gene expression analysis of myocardium from patients with significant MR undergoing left ventricular assist device (LVAD) implantation show increased expression of genes associated with inflammation, and reduced expression of cell energetics and proliferation genes, suggesting that these patients are a distinct subset of patients with cardiomyopathy, which may impact on response to therapies ( 51 ).…”

Section: Mitral Valvementioning

confidence: 99%

Pathophysiology and management of valvular disease in patients with destination left ventricular assist devices

Dimarakis

Callan²,

Khorsandi³

et al. 2022

Front. Cardiovasc. Med.

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Over the last two decades, implantable continuous flow left ventricular assist devices (LVAD) have proven to be invaluable tools for the management of selected advanced heart failure patients, improving patient longevity and quality of life. The presence of concomitant valvular pathology, including that involving the tricuspid, mitral, and aortic valve, has important implications relating to the decision to move forward with LVAD implantation. Furthermore, the presence of concomitant valvular pathology often influences the surgical strategy for LVAD implantation. Concomitant valve repair or replacement is not uncommonly required in such circumstances, which increases surgical complexity and has demonstrated prognostic implications both short and longer term following LVAD implantation. Beyond the index operation, it is also well established that certain valvular pathologies may develop or worsen over time following LVAD support. The presence of pre-existing valvular pathology or that which develops following LVAD implant is of particular importance to the destination therapy LVAD patient population. As these patients are not expected to have the opportunity for heart transplantation in the future, optimization of LVAD support including ameliorating valvular disease is critical for the maximization of patient longevity and quality of life. As collective experience has grown over time, the ability of clinicians to effectively address concomitant valvular pathology in LVAD patients has improved in the pre-implant, implant, and post-implant phase, through both medical management and procedural optimization. Nevertheless, there remains uncertainty over many facets of concomitant valvular pathology in advanced heart failure patients, and the understanding of how to best approach these conditions in the LVAD patient population continues to evolve. Herein, we present a comprehensive review of the current state of the field relating to the pathophysiology and management of valvular disease in destination LVAD patients.

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Mitral regurgitation severity at left ventricular assist device implantation is associated with distinct myocardial transcriptomic signatures

Cited by 5 publications

References 62 publications

Prognostic value of mitral regurgitation in patients undergoing left ventricular assist device deployment: A systematic review and meta‐analysis

Prognostic value of mitral regurgitation in patients undergoing left ventricular assist device deployment: A systematic review and meta‐analysis

Role of the mitral valve in left ventricular assist device pathophysiology

Pathophysiology and management of valvular disease in patients with destination left ventricular assist devices

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