Frequency of Cardiac Valvulopathies in Patients With Marfan Syndrome: A Systematic Review and Meta-Analysis

Abstract

Marfan syndrome (MFS) is a progressive connective tissue disease with a broad range of clinical manifestations. We sought to establish the spectrum of structural valvular abnormalities as cardiovascular involvement has been identified as the most life-threatening aspect of the syndrome. This was a systematic review with a meta-analysis of studies indexed in Medline from the inception of the database to November 7, 2022. Using the random-effects model, separate Forest and Galbraith plots were generated for each valvular abnormality assessed. Heterogeneity was assessed using the I² statistics whilst funnel plots and Egger's test were used to assess for publication bias. From a total of 35 studies, a random-effects meta-analysis approximated the pooled summary estimates for the prevalence of cardiac valve abnormalities as mitral valve prolapse 65% (95% CI: 57%-73%); mitral valve regurgitation 40% (95% CI: 29%-51%); aortic valve regurgitation 40% (95% CI: 28%-53%); tricuspid valve prolapse 35% (95% CI: 15%-55%); and tricuspid valve regurgitation 43% (95% CI: 8%-78%). Only one study reported on the involvement of the pulmonary valve (pulmonary valve prolapse was estimated at 5.3% (95% CI: 1.9%-11.1%) in a cohort of 114 patients with MFS). We believe this study provides a description of the structural valvular disease spectrum and may help inform providers and patients in understanding the clinical history of MFS in the current treatment era with its increased life expectancy.

Keywords: aortic valve; cardiac; marfan syndrome; mitral valve; prevalence; pulmonary valve; tricuspid valve; valvular disease.

Figure 1. PRISMA search flow diagram for inclusion of articles in the meta-analysis

PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analysis, MFS: Marfan syndrome

Figure 2. Forest plot for studies reporting on the prevalence of mitral valve prolapse

De Backer et al. [22], Fan et al. [23], Brown et al. [24], Roman et al. [25], Gillinov et al. [26], Bruno et al. [27], Lacro et al. [28], Attias et al. [29], Wozniak-Mielczarek et al. [30], Ozdemir et al. [31], Gu et al. [32], Rybczynski et al. [33], Mueller et al. [34], Seo et al. [35], Marsalese et al. [36], Tayel et al. [37], Kunkala et al. [38], Pyeritz et al. [39], van Karnebeek et al. [40], Veldhoen et al. [41], Lopez et al. [42], Geva et al. [43], Sisk et al. [44], Hirata et al. [45], Figueiredo et al. [46], Come et al. [47], Freed et al. [48], Pan et al. [49], Yetman et al. [50], Taub et al. [51], Geva et al. [52], Espınola-Zavaleta et al. [21] The Americas = AMR; European Region = EUR; Western Pacific Region = WPR

Figure 3. Forest plot for studies reporting on the prevalence of mitral valve regurgitation

De Backer et al. [22], Fan et al. [23], Forteza et al. [53], Svensson et al. [54], Gillinov et al. [26], Lacro et al. [28], Attias et al. [29], Wozniak-Mielczarek et al. [30], Ozdemir et al. [31], Gu et al. [32], Rybczynski et al. [33], Mueller et al. [34], Seo et al. [35], Tayel et al. [37], Pyeritz et al. [39], van Karnebeek et al. [40], Veldhoen et al. [41], Lopez et al. [42], Sisk et al. [44], Hirata et al. [45], Davis et al. [55], Yetman et al. [50], Geva et al. [52] The Americas = AMR; European Region = EUR; Western Pacific Region = WPR

Figure 4. Forest plot for studies reporting on the prevalence of aortic valve regurgitation

Forteza et al. [53], Svensson et al. [54], Roman et al. [25], Gillinov et al. [26], Wozniak-Mielczarek et al. [30], Ozdemir et al. [31], Gu et al. [32], Mueller et al. [34], Seo et al. [35], Marsalese et al. [36], Tayel et al. [37], van Karnebeek et al. [40], Lopez et al. [42], Geva et al. [43], Hirata et al. [45], Nguyen et al. [56], Davis et al. [55], Geva et al. [52] The Americas = AMR; European Region = EUR; Western Pacific Region = WPR

Figure 5. Forest plot for studies reporting on the prevalence of tricuspid valve prolapse

Wozniak-Mielczarek et al. [30], Ozdemir et al. [31], Gu et al. [32], Mueller et al. [34], Seo et al. [35], Geva et al. [43], Pan et al. [49], Geva et al. [52], Espinola-Zavaleta et al. [21] The Americas = AMR; European Region = EUR; Western Pacific Region = WPR

Figure 6. Forest plot for studies reporting on the prevalence of tricuspid valve regurgitation

Forteza et al. [53], Gu et al. [32], Mueller et al. [34], Seo et al. [35], Geva et al. [52]