Patients with fulminant myocarditis supported with veno-arterial extracorporeal membrane oxygenation: a systematic review and meta-analysis of short-term mortality and impact of risk factors

In this systematic review and meta-analysis, consisting of 54 studies including a total of 2388 FM patients on VA-ECMO, we showed that the pooled estimate of short-term mortality in FM patients on VA-ECMO was 35% (95% CI 29–40%). Older age was the only factor associated with higher short-term mortality, explaining 28% of the variation in results across studies. The probability of receiving a VAD or HTx after VA-ECMO implant was low, and the probability of receiving a HTx was even lower in patients who received LV unloading during VA-ECMO support. These results remained consistent regardless of continent and the risk of bias category. The most frequent major complications included blood transfusions/bleeding, as well as acute kidney injury requiring dialysis, and infections.

Relation to previous workPooled analyses

To date, there are no large clinical trials evaluating outcomes in FM patients supported with VA-ECMO. In this context, the performance of pooled analyses ascertains outcomes and the effect of prognostic factors more precisely. A previously conducted meta-analysis by Chen et al. [15] reported a pooled estimate of in-hospital mortality of 33% (95% CI 26–41%) in 170 FM patients requiring VA-ECMO across 6 studies, which is comparable to our pooled estimate of short-term mortality (35%; 95% CI 29–40%). However, some differences are worth mentioning. Whereas Chen et al. [15] only included full-text studies in English and with 10 or more FM patients published between 2000 and 2012, we had broader inclusion criteria (both full-text studies and abstracts in any language with 5 or more FM patients published in 2009–2022). In addition, Chen et al. [15] only included in-hospital mortality, whereas we included 30-day mortality, death during index hospitalization, and death on VA-ECMO. Based on our expanded inclusion criteria, we included a total of 54 studies, of which 50 were published after 2012. As a result of the larger number of patients with FM on VA-ECMO included in the present study, we were able to report a more precise pooled estimate of short-term mortality with narrower confidence intervals. We were also able to explore heterogeneity and showed that older age increased short-term mortality. Furthermore, as we only included studies published after 2009, our results represent more contemporary VA-ECMO strategies and patient management.

The favorable results of VA-ECMO in FM patients are noticeably highlighted when the usage of VA-ECMO is compared across different etiologies. In a recent large systematic review and meta-analysis of 29,289 CS patients supported with VA-ECMO, Alba et al. [16], in a more restrictive analysis, showed a low pooled estimate of short-term mortality of FM patients of 40% (95% CI 33–46%) compared to other etiologies such as post-myocardial infarction (60%; 95% CI 57–64%), and heart failure (53%; 95% CI 46–59%). The association of lower mortality in FM patients supported with VA-ECMO could be partly explained by the nature of the disease, in which the probability of myocardial recovery is high if the hemodynamic status can be maintained. In contrast, cardiac recovery is less likely in other etiologies based on the presence of irreversible myocardial injury [17, 18].

Impact of risk factors on short-term mortality

Our finding of favorable results of VA-ECMO in FM patients who are younger is consistent with the ECMO literature [17, 19,20,21]. For instance, in one study of 135 FM patients who received VA-ECMO, the mean age of survivors was lower (51.9 ± 17.6 years) than non-survivors (62.1 ± 15.4 years) [19]. Evidence indicates that the poor prognosis in the elderly is probably due to comorbidities with advanced age [20]. In contrast to previous work [21], we did not find a benefit of VA-ECMO initiation in those without cardiac arrest. In addition, our finding that sex did not influence short-term mortality of FM patients on VA-ECMO is in accordance with some but not all of the ECMO literature [22, 23]. The fact that these studies are confined to small cohorts or single centers might contribute to the conflicting results.

Short-term mortality risk is of the utmost importance when deciding on the utility of treatment, particularly when considering a very resource intensive and costly intervention such as VA-ECMO [24]. This underlines the importance of identifying predictors that determine which patient groups have the highest chance of survival. This systematic review found that only 3 small mostly single-center studies (including 180 of the 2388 FM patients) reported on predictors. Moreover, these 3 studies reported on different predictors associated with short-term mortality and with only a very small overlap among the studies, making it difficult to pool together the effect estimates of the predictors and use these to guide clinical decisions. In addition, other factors impacting short-term mortality during VA-ECMO support (i.e., comorbidities, peak lactate level, liver injury, respiratory status, or renal function) were poorly reported (see Supplementary Table S2). Differences in these factors could perhaps explain variation in short-term mortality across studies. Consequently, it is of utmost importance to identify predictors which may aid clinicians in timely decision-making for VA-ECMO initiation in FM.

Complications

The complication rates in the present study were rather high. However, each complication was only reported in 2 to 8 studies, and consequently the variability of each complication was very high among studies. For instance, blood transfusions were reported in only 2 studies with a range of 0 to 100%, and bleeding was reported in 6 studies with a range of 23 to 59%. In addition, it is worth noting that several of the complications were not necessarily complications related to VA-ECMO but rather to the underlying disease of FM.

Coronavirus disease 2019

Myocarditis due to coronavirus disease 2019 (COVID-19) is a severe complication of the disease. Studies evaluating outcomes and management of patients with COVID-19 myocarditis are scarce. In addition, due to the respiratory compromise of COVID-19 patients, some patients received primarily ECMO for respiratory failure associated with subsequent multi-organ failure [25]. In an international cohort study of the Extracorporeal LIFE Support Organization (ELSO) registry, 1035 patients with COVID-19 received ECMO support (including both VA and venous-venous) at 213 hospitals in 36 countries. Of these, only 22 (2%) had myocarditis. However, separate mortality rates for the myocarditis patients were not reported [26]. Most of the evidence on mortality rates in FM patients with COVID-19 who receive VA-ECMO treatment comes from case reports [27,28,29]. Zeng et al. [27] reported the first case of COVID-19-induced FM in a 63-year-old male requiring VA-ECMO as a successful bridge to recovery. Since then, others have reported similar success of VA-ECMO as a bridge to recovery in COVID-19-induced FM in both sexes [28, 29]. Whether the pooled mortality estimate reported in this meta-analysis could be extrapolated to COVID-19 FM patients remains uncertain as COVID-19 infection presents with particular characteristics including respiratory failure and pro-thrombotic risk among others.

Implications for clinical practice and future research

The pooled results of this meta-analysis indicate that VA-ECMO should be considered in FM patients with cardiac failure who have failed conventional therapies, especially in younger patients. However, although a meta-analysis on aggregate study data may offer additional information over individual study reports, there is still a high variation in the results across studies with insufficient exploration of the different sources of heterogeneity. Thus, future research should focus on the performance of individual patient data meta-analysis, registry, or multicenter large prospective cohort studies, which offer improved quality of data and more robust analyses than meta-analysis on aggregate study data ensuing more reliable results. In addition, it is worth noting that the present study does not inform us of whether or not patients with FM should receive VA-ECMO, it only tells us what to expect if we choose this modality. Many patients with FM can be managed with inotropes alone and thereby avoid ECMO related complications. This notion is supported by clinical experience, as well as by previous work where not all FM patients were treated with ECMO, and they still had a good prognosis [30, 31]. However, due to ethical constraints, research studies comparing outcomes in FM patients treated with and without VA-ECMO are at risk of reporting biased worse outcomes in patients supported with VA-ECMO due to patient selection bias. Future research should focus on identifying characteristics of patients supported with VA-ECMO who would benefit more or less.

Strengths and limitations

A major strength of the present systematic review and meta-analysis is that we adapted broad inclusion criteria and included all cohort studies published after 2009 evaluating short-term mortality on VA-ECMO in FM patients. We defined explicit study eligibility criteria and assessed eligibility in duplicate. We followed the same approach to assess the quality of the individual studies eligible for inclusion (risk of bias) and for the data extraction. A final strength of our review is the use of the GRADE approach to rate our certainty in the pooled estimates. Some limitations should also be considered. First, all of the data collected was observational and retrospective in nature. Second, we pooled different definitions of short-term mortality together (i.e., mortality on ECMO, mortality at 30 days, mortality during index hospitalization) due to the limited studies and varied definitions in the literature available. This could have introduced some heterogeneity. However, Alba et al. [16] showed that in a sub-analysis of their meta-analysis of 58 studies, where each study reported on both 30-day mortality and death during index hospitalization, and where the two endpoints were compared, there was no significant difference in the risk estimates. Third, the management of VA-ECMO encompasses a multidisciplinary approach and has changed over time, leading to improved outcomes. To capture this change and report on contemporary patient outcomes, we arbitrarily limited the search to studies published after 2009. However, this strategy does not entirely address this issue, potentially leading to overestimation of mortality. Fourth, factors impacting short-term mortality during VA-ECMO support were poorly reported, and only included a small proportion of the total population of 2388 FM patients, making it difficult to explore whether these factors could perhaps explain variation in short-term mortality across studies. Fifth, we included studies with 5 or more FM patients, and therefore center volume and experience may also influence outcomes such that higher-volume centers report on lower mortality than low-volume centers [32]. The total number of cases performed at each center was not reported. Sixth, the verification of FM by histological findings was not carried out in all studies, and the indications for the initiation of VA-ECMO were not uniform among studies.

留言 (0)

沒有登入
gif