Effectiveness of aortic valve replacement in Heyde syndrome: a meta-analysis

Abstract

Aims: Heyde syndrome is the co-occurrence of aortic stenosis, acquired von Willebrand syndrome, and gastrointestinal bleeding. Aortic valve replacement has been demonstrated to resolve all three associated disorders. A systematic review and meta-analysis were performed to obtain best estimates of the effect of aortic valve replacement on acquired von Willebrand syndrome and gastrointestinal bleeding.

Methods and results: A literature search was performed to identify articles on Heyde syndrome and aortic valve replacement up to 25 October 2022. Primary outcomes were the proportion of patients with recovery of acquired von Willebrand syndrome within 24 h (T1), 24-72 h (T2), 3-21 days (T3), and 4 weeks to 2 years (T4) after aortic valve replacement and the proportion of patients with cessation of gastrointestinal bleeding. Pooled proportions and risk ratios were calculated using random-effects models. Thirty-three studies (32 observational studies and one randomized controlled trial) on acquired von Willebrand syndrome (n = 1054), and 11 observational studies on gastrointestinal bleeding (n = 300) were identified. One study reported on both associated disorders (n = 6). The pooled proportion of Heyde patients with acquired von Willebrand syndrome recovery was 86% (95% CI, 79%-91%) at T1, 90% (74%-96%) at T2, 92% (84%-96%) at T3, and 87% (67%-96%) at T4. The pooled proportion of Heyde patients with gastrointestinal bleeding cessation was 73% (62%-81%). Residual aortic valve disease was associated with lower recovery rates of acquired von Willebrand syndrome (RR 0.20; 0.05-0.72; P = 0.014) and gastrointestinal bleeding (RR 0.57; 0.40-0.81; P = 0.002).

Conclusion: Aortic valve replacement is associated with rapid recovery of the bleeding diathesis in Heyde syndrome and gastrointestinal bleeding cessation. Residual valve disease compromises clinical benefits.

Keywords: Acquired von Willebrand syndrome; Angiodysplasias; Aortic stenosis; Aortic valve replacement; Gastrointestinal bleeding; Heyde syndrome.

Structured Graphical Abstract

Heyde syndrome is effectively treated by aortic valve replacement.

Figure 1

Flowchart of included studies. Adapted from Preferred Reporting Items for Systematic Reviews and Meta-Analyses. (A) Studies were performed by the same research group and had an overlap in inclusion period and follow-up time with one or multiple included studies. (B) One study reported on both gastrointestinal bleeding and Acquired von Willebrand syndrome. (C) Studies reported on the primary outcome(s). GIB, gastrointestinal bleeding; AVWS, acquired von Willebrand syndrome.

Figure 2

Forest plot on acquired von Willebrand syndrome recovery. Plot shows the proportion of patients with recovery of acquired von Willebrand syndrome after aortic valve replacement. Studies are sorted by follow-up time. Recovery of acquired von Willebrand syndrome is divided into four separate time frames. For studies that analysed recovery of acquired von Willebrand syndrome with multiple laboratory studies, the von Willebrand factor multimer distribution was selected. If not provided, von Willebrand factor ratio normalization was selected over closure time adenosine diphosphate/bleeding time. AVWS, acquired von Willebrand syndrome; vWF, von Willebrand factor; CT-ADP, closure time adenosine diphosphate.

Figure 3

Forest plot on gastrointestinal bleeding cessation. Plot shows the proportion of patients with complete cessation of gastrointestinal bleeding after aortic valve replacement. GIB, gastrointestinal bleeding.

Figure 4

Forest plot on the influence of residual aortic valve disease on acquired von Willebrand syndrome recovery. Plots show the risk ratios of patients with a patient–prosthesis mismatch, in purple, or paravalvular leakage, in blue, to recover from acquired von Willebrand syndrome compared with patients without residual valve disease during four time frames after aortic valve replacement. Three studies looked at the influence of patient–prosthesis mismatch, which was defined as an effective orifice area of <0.8, or <0.85 cm²/m^2, of body surface area. Eight studies looked at the influence of paravalvular leakage, which was mostly defined as >mild or as a circumferential extent of aortic regurgitation >10% measured with transthoracic echocardiography.^,,,,, One study defined paravalvular leakage as trace to severe. One study defined paravalvular leakage as significant.

Figure 5

Forest plot on periprocedural bleeding in Heyde syndrome. Plots show the risk ratios of patients with Heyde syndrome to experience periprocedural bleeding and periprocedural gastrointestinal bleeding in comparison to non-Heyde patients (controls). Heyde syndrome consisted of severe aortic stenosis and acquired von Willebrand syndrome (top) or gastrointestinal bleeding (middle and bottom). Periprocedural bleeding was defined as in-hospital access- or non-access-related bleeding. Two studies limited bleeding to ≤24 and ≤72 h after AVR, respectively. Bleeding was scored according to BARC or VARC-2 (some excluding minor^,,, or minor and major bleeding). GIB, gastrointestinal bleeding