Data on the safety and efficacy of transcatheter aortic valve replacement (TAVR) for the treatment of aortic valve stenosis in immunocompromised (IC) patients is scarce, while it represents a valid alternative to surgical AVR in this vulnerable population. This meta-analysis aims to compare the clinical outcomes of TAVR in IC versus non-IC patients. A comprehensive search was conducted across PubMed, EMBASE, and Cochrane Central for randomized controlled trials and observational studies that compared outcomes between IC and non-IC patients undergoing TAVR. Primary outcomes included 1-year all-cause, cardiovascular (CV) and non-CV mortality. Secondary outcomes included new permanent pacemaker implantation (PPI) and major periprocedural complications. 4,478 patients in 7 studies (mean age 80.5 years, 7.64% IC) were included in the analysis. As compared with non-IC patients, IC patients exhibited a similar 30-day death rate (Odds Ratio [OR] 1.62; 95% Confidence Interval [CI] 0.68 to 3.98; p = 0.297), but significantly higher 1-year all-cause mortality (OR 2.39; 95% CI 1.55 to 3.70; p <0.001). Notably, IC patients demonstrated a lower risk of CV death (OR 0.24; 95% CI 0.10 to 0.59; p = 0.002) but a higher risk of non-CV death (OR 4.16; 95% CI 1.70 to 10.18; p = 0.002). There was no difference in the rate of new PPI or major periprocedural complications. In conclusion, TAVR is a safe and effective treatment strategy in IC patients, with similar short-term mortality and increased medium-term mortality risk as compared with non-IC patients. (PROSPERO: CRD42024623229)
Aortic valve stenosis (AS) represents a significant burden in modern cardiovascular medicine, with its prevalence rising in an aging population at increasing cardiovascular risk. Transcatheter aortic valve replacement (TAVR) has transformed treatment paradigms, expanding from high-risk to intermediate- and low-risk patients, supported by robust evidence from landmark trials. ,, However, immunocompromised (IC) patients, often burdened by comorbidities such as malignancies or chronic inflammatory conditions, present unique challenges due to altered wound healing, dysregulated inflammation, and heightened infection risk. Recent data suggest a paradox: IC patients undergoing TAVR face higher all-cause mortality but potentially lower cardiovascular mortality compared to non-IC patients, with TAVR showing advantages over surgical aortic valve replacement (SAVR) in severe comorbidities. ,, Despite these insights, current evidence is limited by heterogeneous study designs, small sample sizes, and inconsistent definitions of immunosuppression, obscuring the true impact on mortality and morbidity. This meta-analysis aims to address these gaps by systematically comparing clinical outcomes of TAVR in IC versus non-IC patients, pooling multistudy data to elucidate mortality, morbidity, and optimal management strategies for this vulnerable population.
Methods
Study design
This systematic review and meta-analysis was performed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Statement guidelines and the Cochrane Collaboration Handbook for Systematic Reviews of Interventions guidelines. The prospective meta-analysis protocol has been uploaded to the International Prospective Register of Systematic Reviews (PROSPERO; CRD42024623229).
Eligibility criteria
For inclusion, no restrictions were imposed on publication date, publication status, or language. Studies were deemed eligible if they met the following criteria: (1) observational or randomized trials, (2) examining immunocompromised patients undergoing TAVR, and (3) reporting outcomes of all-cause and/or cardiovascular/noncardiovascular (CV/non-CV) mortality at 30 days and/or up to 2 years after the procedure. Data from published studies were included, and no limitations were applied regarding race or ethnicity. Exclusion criteria were as follows: (1) studies not reporting at least one outcome of interest, (2) studies reporting data with no control group, and (3) studies not published in the English language.
Data source and search strategy
We systematically searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed/MEDLINE, and Embase databases from inception through the final search date of December 25th, 2024. Two authors (R.M., P.D.) performed the systematic review independently, with disagreements resolved through a panel discussion among the authors. Study selection involved screening titles and abstracts, followed by a full-text evaluation of potentially eligible studies. The complete search strategy for each database is presented in Figure 1 .
PRISMA flow diagram of study screening and selection.
Data extraction
Four authors (R.M, P.D, A.H, and J.H), working in pairs, independently extracted data from the selected studies using a double-blinded approach. They reviewed both the primary reports and supplementary materials, systematically extracting all relevant information from the included articles. Any discrepancies between the reviewers were resolved through consensus or, when needed, by consulting other members of the review team (L.M, C.D).
Outcomes
Our primary endpoints were (1) 30-day all-cause mortality (2) 1-year all-cause mortality and (3) 2-year all-cause mortality. In addition, we assessed the following secondary endpoints: (4) CV mortality, (5) non-CV mortality, (6) permanent pacemaker implantation (PPI), (7) minor vascular complications, (8) major vascular complications, (9) stroke and (10) acute kidney injury.
Quality assessment
The risk of bias and quality assessment of the included studies were conducted using the Risk of Bias in nonrandomized Studies of Interventions (ROBINS-I) tool. Outcome data were collected based on an intention-to-treat approach. The risk of bias evaluation was performed independently by 2 authors (R.M. and H.A.), with any discrepancies resolved through consensus following a thorough discussion of the differing assessments (C.D.). ,,,,
Statistical analysis
Endpoints were analyzed using odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs). For time-to-event sensitivity analyses, hazard ratios (HRs) with 95% CIs were calculated. Heterogeneity was evaluated using the Cochrane Q statistic and Higgins and Thompson’s I², with the restricted maximum-likelihood estimator. Heterogeneity was categorized as low (I² = 25%), moderate (I² = 50%), or high (I² = 75%). A random-effects model was applied to account for potential variability in effect sizes across studies. Prespecified subgroup interactions were tested using the Q test method under the null hypothesis of no interaction between groups, with results reported as p-values. All p-values are 2-sided, and no adjustments were made for multiple comparisons. Statistical analyses were performed using R version 4.3.2 (R Core Team, Vienna, Austria) with the meta package CRAN. ,,,
Results
Study selection and characteristics
Our initial search yielded 612 results, after removal of duplicate studies and ineligible trials, and 14 articles were selected for full-text review. After a thorough evaluation, 7 studies were included in the systematic analysis providing a more comprehensive understanding of the use of TAVR in the IC patients ( Figure 1 ). ,,,,,, Study characteristics are reported in Table 1 .
Table 1
Baseline characteristics of the included studies and participants
| Trial | Kaihara et al. | Joshi et al. | Ghannam et al. | Walczewski et al. | Fink et al. | Koyama et al. | Gautier et al. | |
|---|---|---|---|---|---|---|---|---|
| Study type | Retrospective cohort study | Retrospective cohort study | Retrospective cohort study | Multicenter, registry-based analysis | Retrospective cohort study | Retrospective cohort study | Prospective cohort study | |
| Study location | Japan | USA | USA | Poland | Israel | Japan | France | |
| Immunosuppressant dose | Prednisone 6.3mg/day | NA | >5 mg/d of prednisone or equivalent | Prednisone (28%), methotrexate and methylprednisolone (12%), methylprednisolone (8%), hydrocortisone (4%), imatinib (4%), cyclophosphamide (4%) | NA | Prednisone 5mg/d | Prednisone 7.5mg/d | |
| Inclusion criteria | Patients with aortic stenosis who underwent TAVR from January 2016 to December 2018 | Patients treated with a transfemoral approach either with the balloon-expandable valve or the self-expanding valve from 2012 to 2020 | All patients who underwent TAVR from January 2015 to December 2019 | Patients with symptomatic severe aortic stenosis who underwent TAVR after local Heart Team consultation | Patients with severe symptomatic aortic stenosis and high or prohibitive operative risk undergoing TAVR via the femoral approach from October 2009 to December 2013 | Patients who had undergone transfemoral TAVR between October 2013 and July 2016 | Patients consecutively treated with TAVR from October 2006 to November 2018 | |
| Sample size | IST | 22 | 99 | 56 | 25 | 25 | 67 | 48 |
| No IST | 260 | 992 | 117 | 75 | 195 | 1,246 | 1,251 | |
| Mean age, y | IST | 81 | 80.2 | 80 | 78 | 78 | 80.9 | 80 |
| No IST | 84 | 81.6 | 83 | 82 | 81 | 84.6 | 81 | |
| Male (%) | IST | 27 | 48.5 | 64 | 60 | 48 | 22.4 | 40 |
| No IST | 33 | 56 | 56 | 53 | 44.1 | 28.2 | 53 | |
| Diabetes mellitus (%) | IST | 27 | 25.3 | 18 | NA | 40 | 37.3 | 21 |
| No IST | 26 | 33.7 | 38 | NA | 37 | 25.3 | 26 | |
| Hypertension (%) | IST | 50 | 89.9 | 82 | NA | 84 | 71.6 | NA |
| No IST | 86 | 90.3 | 94 | NA | 89 | 77.8 | NA | |
| Atrial fibrillation (%) | IST | NA | 63.6 | 43 | NA | 33 | NA | 32 |
| No IST | NA | 61.9 | 44 | NA | 29 | NA | 35 | |
| COPD (%) | IST | NA | 26.3 | 23 | NA | 52 | 13.4 | 21 |
| No IST | NA | 16.5 | 29 | NA | 18 | 17.5 | 15 | |
| Prior MI (%) | IST | NA | 15.2 | 18 | NA | 32 | 3 | NA |
| No IST | NA | 19,7 | 12 | NA | 35 | 7 | NA | |
| Prior PAD (%) | IST | NA | 13.1 | 30 | 20 | 16 | 9 | 19 |
| No IST | NA | 17.3 | 28 | 20 | 9 | 10 | 21 | |
| Smoking (%) | IST | 5 | 5.1 | 2 | NA | 12 | 18 | NA |
| No IST | 4 | 4 | 5 | NA | 14 | 19 | NA | |
| Mean LVEF (%) | IST | 71 | 56.6 | 58 | 50 | 50 | 64.6 | 55 |
| No IST | 65 | 56.5 | 60 | 55 | 56 | 61.8 | 23 | |
| Self-expanding valves (%) | IST | 9 | 33 | 38 | 60 | 52 | 6 | 45 |
| No IST | 15 | 24 | 31 | 72 | 69 | 10.4 | 39 | |
| Median STS score | IST | 5.4 | 10.6 | 4.2 | NA | 6.6 | 7.1 | NA |
| No IST | 5 | 9.8 | 4.4 | NA | 5.4 | 6.5 | NA | |
| AV mean gradient (mm Hg) | IST | 42 | 40.4 | 41 | NA | 41.2 | 49.1 | 47 |
| No IST | 41 | 42.6 | 40 | NA | 45.9 | 51.3 | 48 | |
| Median Follow up | 567 d | 30 d | 510 d | 985 d | 763 d | 297 d | 365 d | |
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