What is the clinical evidence from this study?

Study design: Observational. Population: Chronic severe primary mitral regurgitation (n=120). Intervention: Chronic severe primary mitral regurgitation vs. Autopsy controls without cardiac pathology. Primary outcome: Myocardial fibrosis (collagen volume fraction, CVFmean) (p=<0.001).

January 1, 2020Open Access

Myocardial fibrosis in asymptomatic and symptomatic chronic severe primary mitral regurgitation and relationship to tissue characterisation and left ventricular function on cardiovascular magnetic resonance

Q: What are the key findings of this study?

Patients with chronic severe primary mitral regurgitation had significantly higher myocardial fibrosis compared to autopsy controls (median CVFmean 14.6% vs 3.3%, P<0.001), a difference that was present even before the onset of symptoms.

Key Result

Patients with chronic severe primary mitral regurgitation had significantly higher myocardial fibrosis compared to autopsy controls (median CVFmean 14.6% vs 3.3%, P<0.001), a difference that was present even before the onset of symptoms.

Study Design

Type

Observational (n=120)

Blinding

Blinded analysis of histology and CMR

Multicenter

Yes

Structured PICO

Does cardiovascular magnetic resonance-derived extracellular volume correlate with histological myocardial fibrosis, left ventricular function, and exercise capacity in patients with chronic severe primary mitral regurgitation?

Population

120 adult patients (mean age 64, 29% female) with chronic severe primary degenerative mitral regurgitation referred for surgery, compared to 8 autopsy controls.

Exposure

Assessment of myocardial fibrosis via left ventricular biopsy during mitral valve surgery and cardiovascular magnetic resonance (CMR) imaging.

Comparator

Autopsy controls without cardiac pathology (for histological comparison).

Outcome

Characterisation of myocardial fibrosis on histology (collagen volume fraction, CVFmean) and comparison to tissue characterisation on cardiovascular magnetic resonance (CMR) imaging (ECV, native T1, LGE).surrogate

In patients with chronic severe primary mitral regurgitation, myocardial fibrosis is increased even before symptom onset, and CMR-derived extracellular volume serves as a useful global marker of myocardial status that correlates with LV function and exercise capacity.

Main Result

Absolute Event Rate: 14.6% vs 3.3%

p-value: p=<0.001

Limitations

Observational study design precludes inferring causation.
Invasive myocardial biopsy was not performed in all patients due to technical difficulties.
Unable to anatomically match the location of autopsy sections with histological biopsies.
Difficult to anatomically match biopsy locations with late gadolinium enhancement (LGE).
Invasive measurement of pulmonary artery pressures was not performed in all patients.
Narrow range of global fibrosis quantified by ECV may have weakened the ability to detect correlations.

Abstract

BACKGROUND: Myocardial fibrosis occurs in end-stage heart failure secondary to mitral regurgitation (MR), but it is not known whether this is present before onset of symptoms or myocardial dysfunction. This study aimed to characterise myocardial fibrosis in chronic severe primary MR on histology, compare this to tissue characterisation on cardiovascular magnetic resonance (CMR) imaging, and investigate associations with symptoms, left ventricular (LV) function, and exercise capacity. METHODS: ) compared to autopsy controls without cardiac pathology. RESULTS: max: R = - 0.22, P = 0.030). CONCLUSIONS: Patients with chronic primary MR have increased fibrosis before the onset of symptoms. Due to the patchy nature of fibrosis, CMR derived ECV may be a better marker of global myocardial status. Clinical trial registration Mitral FINDER study; Clinical Trials NCT02355418, Registered 4 February 2015, https://clinicaltrials.gov/ct2/show/NCT02355418.

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