What is the clinical evidence from this study?

Study design: Observational. Population: Chronic Atrial Fibrillation in Primary Mitral Regurgitation (n=59). Intervention: Atrial fibrillation vs. Sinus rhythm. Primary outcome: Differentially expressed genes (defined using 1.5-fold change).

October 15, 2021Cardiovascular TherapeuticsOpen Access

Molecular Signatures of Human Chronic Atrial Fibrillation in Primary Mitral Regurgitation

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Key result

Persistent AF in primary MR is linked to increased expression of HF transition genes.

n=59

Why the study?

Transcriptomics of atrial fibrillation in the setting of chronic primary mitral regurgitation remained to be characterized.

Does persistent atrial fibrillation alter gene expression profiles and structural remodeling compared to sinus rhythm in patients with primary mitral regurgitation?

Study Design

Type

Observational (n=59)

Structured PICO

Does persistent atrial fibrillation alter gene expression profiles and structural remodeling compared to sinus rhythm in patients with primary mitral regurgitation?

Population

59 patients with degenerative primary mitral regurgitation (MR)

Intervention

Persistent atrial fibrillation (AFib)

Comparator

Sinus rhythm (SR)

Outcome

Differentially expressed genes (using 1.5-fold change threshold) and ultrastructural atrial remodelingsurrogate

Persistent atrial fibrillation in patients with primary mitral regurgitation is associated with distinct transcriptomic alterations linked to heart failure transition, structural, and electrical remodeling.

Implication

Persistent AF may mark accelerated remodeling in primary MR; hypothesis-generating for rhythm interventions, needing prospective validation.

Abstract

Objectives. Transcriptomics of atrial fibrillation (AFib) in the setting of chronic primary mitral regurgitation (MR) remains to be characterized. We aimed to compare the gene expression profiles of patients with degenerative MR in AFib and sinus rhythm (SR) for a clearer picture of AFib pathophysiology. Methods. After transcriptomic analysis and bioinformatics ( <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:mi>n</a:mi> <a:mo>=</a:mo> <a:mn>59</a:mn> </a:math> ), differentially expressed genes were defined using 1.5-fold change as the threshold. Additionally, independent datasets from GEO were included as meta-analyses. Results. QRT-PCR analysis confirmed that AFib persistence was associated with increased expression molecular changes underlying a transition to heart failure (NPPB, <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"> <c:mi>P</c:mi> <c:mo>=</c:mo> <c:mn>0.002</c:mn> </c:math> ; ANGPTL2, <e:math xmlns:e="http://www.w3.org/1998/Math/MathML" id="M3"> <e:mi>P</e:mi> <e:mo>=</e:mo> <e:mn>0.002</e:mn> </e:math> ; IGFBP2, <g:math xmlns:g="http://www.w3.org/1998/Math/MathML" id="M4"> <g:mi>P</g:mi> <g:mo>=</g:mo> <g:mn>0.010</g:mn> </g:math> ), structural remodeling including changes in the extracellular matrix and cellular stress response (COLQ, <i:math xmlns:i="http://www.w3.org/1998/Math/MathML" id="M5"> <i:mi>P</i:mi> <i:mo>=</i:mo> <i:mn>0.003</i:mn> </i:math> ; COMP, <k:math xmlns:k="http://www.w3.org/1998/Math/MathML" id="M6"> <k:mi>P</k:mi> <k:mo>=</k:mo> <k:mn>0.028</k:mn> </k:math> ; DHRS9, <m:math xmlns:m="http://www.w3.org/1998/Math/MathML" id="M7"> <m:mi>P</m:mi> <m:mo>=</m:mo> <m:mn>0.038</m:mn> </m:math> ; CHGB, <o:math xmlns:o="http://www.w3.org/1998/Math/MathML" id="M8"> <o:mi>P</o:mi> <o:mo>=</o:mo> <o:mn>0.038</o:mn> </o:math> ), and cellular stress response (DNAJA4, <q:math xmlns:q="http://www.w3.org/1998/Math/MathML" id="M9"> <q:mi>P</q:mi> <q:mo>=</q:mo> <q:mn>0.038</q:mn> </q:math> ). Furthermore, AFib persistence was associated with decreased expression of the targets of structural remodeling (BMP7, <s:math xmlns:s="http://www.w3.org/1998/Math/MathML" id="M10"> <s:mi>P</s:mi> <s:mo>=</s:mo> <s:mn>0.021</s:mn> </s:math> ) and electrical remodeling (CACNB2, <u:math xmlns:u="http://www.w3.org/1998/Math/MathML" id="M11"> <u:mi>P</u:mi> <u:mo>=</u:mo> <u:mn>0.035</u:mn> </u:math> ; MCOLN3, <w:math xmlns:w="http://www.w3.org/1998/Math/MathML" id="M12"> <w:mi>P</w:mi> <w:mo>=</w:mo> <w:mn>0.035</w:mn> </w:math> ) in both left and right atrial samples. The transmission electron microscopic analysis confirmed ultrastructural atrial remodeling and autophagy in human AFib atrial samples. Conclusions. Atrial cardiomyocyte remodeling in persistent AFib is closely linked to alterations in gene expression profiles compared to SR in patients with primary MR. Study findings may lead to novel therapeutic targets. This trial is registered with ClinicalTrials.gov identifier: NCT00970034.

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Cite This Study

Deniz et al. (2021) conducted an observational in Chronic Atrial Fibrillation in Primary Mitral Regurgitation (n=59). Atrial fibrillation vs. Sinus rhythm was evaluated on Differentially expressed genes (defined using 1.5-fold change). Persistent atrial fibrillation in primary mitral regurgitation was associated with increased expression of genes underlying heart failure transition, such as NPPB (P=0.002), compared to sinus rhythm.

synapsesocial.com/papers/6a163de1fd647e582a608124 https://doi.org/10.1155/2021/5516185