What does this research mean for the field?

In patients with severe aortic stenosis, myocardial fibrosis load strongly correlates with regional longitudinal strain impairment and is associated with elevated inflammatory markers and increased mortality. Novelty: ClaimNovelty.CONFIRMATORY. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To assess the role of local and systemic inflammation in left ventricular fibrosis and contractile dysfunction among patients with severe aortic stenosis, and to evaluate the diagnostic utility of 2D-strain echocardiography and circulating biomarkers.

May 21, 2019ESC Heart FailureOpen Access

Causes and Consequences of Cardiac Fibrosis in Patients Referred for Surgical Aortic Valve Replacement

Q: What are the key findings of this study?

Regional longitudinal strain strongly correlated with myocardial fibrosis load (R = 0.83) in severe aortic stenosis, with severe fibrosis linked to elevated inflammatory markers and higher mortality.

Q: What is the clinical evidence from this study?

Study design: Observational. Population: Severe aortic stenosis (n=58). Intervention: Myocardial fibrosis and systemic inflammation vs. Mild or moderate fibrosis load. Primary outcome: Correlation between regional longitudinal strain (S1) and myocardial fibrosis load (R = 0.83, p=<0.0001).

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Key result

Regional longitudinal strain strongly correlates with myocardial fibrosis load in severe AS, tracking higher mortality.

R = 0.83
P<0.0001
n=58

Why the study?

Cardiac fibrosis is associated with LV remodelling and contractile dysfunction in aortic stenosis, but the underlying fibrotic process remains unclear.

Population

58 patients with aortic stenosis referred for surgical valve replacement

Comparison

Fibrosis severity tertiles (mild vs moderate vs severe load)

Design

Prospective consecutive observational study

Authors

AGArnault GalatCentre Hospitalier Universitaire Henri-Mondor AGAziz GuellichUniversité Paris-Est Créteil DBDiane BodezCentre Cardiologique du Nord

Discussion

Member takes

Implication

May inform noninvasive fibrosis assessment in severe AS; hypothesis-generating for anti-inflammatory interventions pending prospective validation.

Key Points

To assess the role of local and systemic inflammation in left ventricular fibrosis and contractile dysfunction among patients with severe aortic stenosis, and to evaluate the diagnostic utility of 2D-strain echocardiography and circulating biomarkers.
Prospectively and consecutively enrolled 58 patients with severe aortic stenosis referred for surgical aortic valve replacement (mean age 73 ± 11 years).
Conducted comprehensive 2D-strain echocardiography and measured serum cytokines and inflammatory biomarkers using Luminex bead-based assays.
Obtained intraoperative myocardial biopsies of the basal antero-septal segment (S1) stained with Sirius red to quantify fibrosis into tertiles (TF1 to TF3), and performed immunostaining for macrophages, interleukin 6 (IL-6), and glycoprotein 130 (gp130).
Regional S1 strain correlated strongly with quantified myocardial fibrosis load (R = 0.83, P < 0.0001), and global left ventricular longitudinal strain was significantly lower in the highest fibrosis tertile compared with lower tertiles (P = 0.009).
Severe fibrosis (TF3) was associated with higher serum C-reactive protein and IL-6, lower serum gp130 (P < 0.05), and an IL-6 diagnostic AUC of 0.74 (95% CI 0.56–0.93) for identifying severe fibrosis.
Over a median follow-up of 735 days, all 3 patient deaths occurred exclusively in the third fibrosis tertile (P = 0.009 for TF1–2 vs. TF3).

Study Design

Type

Observational (n=58)

Multicenter

Structured PICO

Population

58 patients (mean age 73 years, 41% female) with severe aortic stenosis referred for surgical aortic valve replacement, followed for a median of 735 days.

Outcome

Correlation between 2D-strain echocardiography, serum biomarkers, and cardiac fibrosis load (quantified by myocardial biopsy)surrogate

Main Result

Effect estimate: R = 0.83

p-value: p=<0.0001

In patients with severe aortic stenosis, elevated inflammatory markers and impaired regional strain correlate strongly with myocardial fibrosis load, which is associated with worse clinical outcomes.

Limitations

Per-surgical biopsies were limited to specific areas of the endomyocardium, not necessarily representative of the whole wall's thickness
Small sample size
Full signalling pathways and molecular mechanisms were not detailed
Polymorphism in the promoter region of IL-6 was not investigated
Only three patients died during follow-up

Cite This Study

Galat et al. (2019) conducted an observational in Severe aortic stenosis (n=58). Myocardial fibrosis and systemic inflammation vs. Mild or moderate fibrosis load was evaluated on Correlation between regional longitudinal strain (S1) and myocardial fibrosis load (R = 0.83, p=<0.0001). Regional longitudinal strain strongly correlated with myocardial fibrosis load (R = 0.83) in severe aortic stenosis, with severe fibrosis linked to elevated inflammatory markers and higher mortality.

synapsesocial.com/papers/6a1ff3bf35281a23f90daf0d https://doi.org/10.1002/ehf2.12451

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Implication

May inform noninvasive fibrosis assessment in severe AS; hypothesis-generating for anti-inflammatory interventions pending prospective validation.

Causes and Consequences of Cardiac Fibrosis in Patients Referred for Surgical Aortic Valve Replacement

Discussion

Member takes

Implication

Key Points

Study Design

Structured PICO

Main Result

Limitations

Cite This Study

Causes and Consequences of Cardiac Fibrosis in Patients Referred for Surgical Aortic Valve Replacement

Discussion

Member takes

Implication

Key Points

Study Design

Structured PICO

Main Result

Limitations

Cite This Study

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