Coronary microvascular dysfunction in patients undergoing transcatheter aortic valve implantation: A systematic review and meta-analysis

Figures

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  Fig 1. PRISMA 2020 flow diagram. Among the 708 records identified, 319 duplicates were removed. The remaining 389 unique records were screened, and 31 underwent full-text review. Twelve records were included in the analysis (11 in the primary synthesis, and Gallinoro et al. [21] was included in the sensitivity analyses). The reasons for exclusion during the full-text review are listed in S10 Table. Reporting follows the PRISMA 2020 guidelines [14].

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  Fig 2. Prevalence of coronary microvascular dysfunction (CMD) by diagnostic modality (random-effects forest plot). Wire-based pool (k = 6, n = 324): pooled prevalence = 46.8% (95% confidence interval [CI] [34.0, 59.9]; I² = 72%). Angiographic pool (k = 4, n = 888): pooled prevalence = 38.4% (95% CI [35.3, 41.7]; I² = 0%). The combined pool of 1,212 patients yielded a descriptive estimate only due to modality-driven heterogeneity. Random-effects model, DerSimonian–Laird method [2]. CI = confidence interval; CMD = coronary microvascular dysfunction; k = number of studies; n = sample size.

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  Fig 3. Forest plot for change in coronary flow reserve (CFR) after transcatheter aortic valve implantation (TAVI). Random-effects pooled mean difference: + 0.49 (95% confidence interval [+0.27, + 0.71]; I2 = 72%; τ2 = 0.044; k = 5, n = 103 paired observations). † indicates the studies for which Wan et al.’s [24] method was used to estimate the mean ± standard deviation from the median [interquartile range]. The study by Sabbah et al. [12] was excluded because the change in CFR was reported for the mixed cohort only and TAVI-specific paired CFR data were not separately reported. The study by Gallinoro et al. [21] was excluded because it pooled data from Scarsini et al. [21]. CFR = coronary flow reserve; CI = confidence interval; IQR = interquartile range; k = number of studies; MD = mean difference; n = sample size; SD = standard deviation; TAVI = transcatheter aortic valve implantation; τ2=between-study variance.

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  Fig 4. Change in microvascular resistance after transcatheter aortic valve implantation (TAVI). Individual study estimates are grouped by the index construct (Hedges’ g). Standardized mean differences with 95% confidence intervals for the four studies that reported paired measurements. Negative values indicate reduced microvascular resistance after TAVI. The study by Gallinoro et al.[21] was excluded due to cohort overlap. AVR = aortic valve replacement; HMR = hyperemic microvascular resistance; MRR = microvascular resistance reserve; N = sample size; Rμ = absolute minimal microvascular resistance; SMD = standardized mean difference; TAVI = transcatheter aortic valve implantation.

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  Fig 5. Forest plot for exploratory pooled hazard ratio (HR) for major adverse cardiovascular events (log scale). Random-effects pooled HR = 3.22 (95% confidence interval [0.98, 10.60]; I2 = 78%; τ2 = 0.59; k = 2, n = 585). The substantial heterogeneity reflected the use of fundamentally different definitions of coronary microvascular dysfunction (CMD). Scarsini et al. [5] used IMRangio ≥ 30 (HR: 6.67) and Shi et al. [6] used AMR > 250 (HR: 1.94). The study by Shi et al. [8] was excluded because it did not report a dichotomous adjusted HR for AMRr > 490 vs. ≤ 490; its event-rate finding (42.6% vs. 26.8%, p = 0.042) and continuous-scale HR (1.18 per 100-unit AMRr) are reported narratively in section 3.5. The pooled estimate should be regarded as exploratory only. AMR = angiographic microvascular resistance; AMRr = resting angiographic microvascular resistance; CI = confidence interval; CMD = coronary microvascular dysfunction; HR = hazard ratio; IMRangio = angiography-derived index of microcirculatory resistance; k = number of studies; MACE = major adverse cardiovascular events; N = sample size; n = sample size; τ2=between-study variance.