Myocardial performance index to assess cardiac function in spondyloarthritis: A systematic review and meta-analysis

This study aimed to assess the utility of MPI in assessing LV function in SpA patients.

A comprehensive search using MEDLINE, ProQuest, Google Scholar, Scopus and Cochrane Library electronic databases was conducted to gather relevant studies. Three separate authors independently executed this search using our predetermined keywords for Rheumatic Autoimmune Disease and Myocardial Performance Index, with the year of study limited to [1995 (MPI first introduced) – 2023] (Supplementary File 2). The rationale behind using the Rheumatic Autoimmune Disease keywords was the possibility or more than one autoimmune or autoinflammatory disease were discussed in the study. All studies examining the SpA and MPI were included. This article specifically focused on LV MPI in SpA patients as LV MPI was more commonly assessed and LV cardiac dysfunction was more frequently reported than right ventricular (RV) dysfucntion in SpA patients. Consequently, studies that only assessed RV MPI were excluded.

All retrieved studies were exported into Mendeley reference manager software, and then checked for duplication, followed by titles and abstracts screening using Rayyan software. Three authors independently conducted the assessments and studies were excluded when the title and/or abstracts were not appropriate for this review. The selected papers underwent full-text assessment using the aforementioned eligibility criteria. Reasons for exclusion were documented within the program, and the reference lists of included studies were manually screened for additional eligible studies. The study selected for the review was determined by majority agreement.

The following data of included studies were extracted independently: the name of primary author, country of origin, study design, sample sizes, age and gender of participants, disease duration, disease activity, echocardiography method, and the outcome of interest. The three independent authors extracted data from all eligible studies. The same authors independently assessed the included studies with following parameters: incomplete outcome data and selective outcome reporting.

MPI, systolic function and diastolic function in SpA patients and control, were quantified and reported as mean differences.

Two independent reviewers evaluated each study using the Newcastle-Ottawa Scale (NOS) adapted for cross-sectional, case-control, and cohort studies. The NOS tool comprised three domains: selection process, comparability, and outcome. Based on the degree of bias, each study’s overall quality was categorized into three levels according to the total NOS score: very high risk of bias (0 to 3 points), high risk of bias (4 to 6) and low risk of bias (7 to 9), with higher score indicating better methodological quality. Discrepancies in assessments were resolved by discussion among the whole review team until consensus was achieved.

The confidence in cumulative evidence was assessed using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. The GRADE system assessed the quality of evidence for each individual outcome by evaluating factors including the risk of bias within-study (methodological quality), directness of evidence, heterogeneity, precision of effect estimates and risk of publication bias. The overall certainty of evidence was classified into high, moderate, low, or very low quality [24].

All continuous outcomes were presented as mean differences (MDs) and 95% Confidence Intervals (CIs) between each group. We used the Review manager (RevMan; Cochrane Collaboration) version 5.4 to synthesize the pooled data, the heterogeneity, and the power of each study. All synthesized data were presented as forest plots. Some studies reported primary outcomes using different evaluation or calculation methods, therefore the meta-analyses were conducted with a random effects model. However, if the I² value was 0%, the fixed effect model was conducted.

The effect of each trial was plotted by the inverse of its SE in a funnel plot test, which was utilized to investigate any potential publication bias. Heterogeneity across trials was assessed using the I² statistic. Less than 25% of an I² value was regarded as subtle, 25% to 50% as low, 51% to 75% as moderate, and more than 75% as high heterogeneity. Sensitivity analyses were conducted to investigate potential source of the observed heterogeneity. P-values below 0.05 were regarded as significant.

The study selection process and results were presented in a flowchart as shown in Figure 1. Initially, 2239 relevant studies were identified through the search strategy. After removing duplicates, 1694 studies were obtained, with 17 studies being extracted following title and abstract screening. Based on the selection criteria, 16 studies were considered for full-text screening. Five studies did not meet the criteria, among which three did not assess LV MPI index, one study assessed right ventricular MPI index, and one wrong population study. Finally, 11 studies were included in the systematic review, with seven that met eligibility criteria for data extraction being used in meta-analysis.

Figure 1.

PRISMA 2020 Flow Diagram of Included Studies.

The inclusion criteria were met by a total of 11 studies with one study focusing on uSpA and ten studies focusing on AS. The case group included 544 participants (342 males, 202 females) and the control group comprised 453 participants. The characteristics of the included studies were reported in Table 1.

The included studies comprised two cross-sectional and nine case-control studies. Of the 11 studies included, seven were conducted in Turkey, two in Egypt, one in Greece, and one in Brazil [10,20,21,25,26,27,28,29,30,31,32]. This review encompassed a range of SpA conditions, with one study focusing on uSpA and ten studies on AS with mean ages ranged from 33.79±8.84 to 44.69±9.03 years.

The echocardiography techniques in all studies were performed using transthoracic echocardiography, with six studies using conventional echocardiography, four studies using TDI, and one study by Okan et al., utilized both methods to assess the LV systolic and diastolic function as well as MPI [30]. The systolic indices such as LVEF were reported to be significantly lower in AS compared to healthy control only by two studies. In contrast, the diastolic indices such as E/A ratio [mitral inflow early diastolic wave (E)/late diastolic wave (A)] or Em/Am ratio [early diastolic myocardial peak velocity (Em)/late diastolic myocardial peak velocity (Am)] were reported to be significantly different by four included studies. The remaining of included studies demonstrated no significant difference of diastolic and systolic indices.

The disease duration in each study varied, with the shortest duration being at least one year and the longest duration reported as 30.6±9.5 years; data from two studies were not available. The most frequently used scoring to describe the disease activity of AS was BASDAI with values ranging from 1.24±1.13 to 5.01±7.71. Only two out of eleven included studies assessed the MPI with disease activity and duration. Rosa RE et al., found altered MPI was not associated with disease activity (as measured with BASDAI) (p=1.00) but was associated with disease duration. Patients with more than 20 years of disease had higher rates of concentric ventricular remodeling (p=0.02) and altered MPI (p=0.014) than those with less than 20 years disease duration [11]. Moyssakis I et al. demonstrated significant correlation of LV MPI and disease duration (r=0.549, p<0.001) and BASDAI score (r=0.405, p=0.004), but not with BASFI or BASMI score [26].

Kocabas et al. were the only researches to investigate the relationship between MPI and traditional cardiovascular risk factors such as body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) in patients with AS [25]. Their findings showed no significant association between these factors and MPI. In contrast, MPI demonstrated a significant correlation with systemic inflammation, particularly erythrocyte sedimentation rate (ESR) and red cell distribution width (RDW), suggesting a stronger link between inflammation and cardiac function in this patient group. Further details were shown in Table 1.

Among the eleven studies evaluated using NOS, nine were case-control studies (Table 2.A) and two were cross-sectional studies (Table 2.B). Eight of nine case-control studies were considered as having good quality with one case-control study by Kocabas et al., was considered to be of fair quality [25]. All cross-sectional studies were categorized as having good quality.

Overall studies were considered to be good quality by NOS for cross sectional and case-control tools, implying that plausible bias was unlikely to significantly influence the results. Only one study (Kocabas et al., 2018) was designated as fair quality study, as shown in Table 2.A. [25]. The heterogeneity was high for Conventional MPI (cMPI), with I² test results of 87%, while for Tissue Doppler MPI (tdMPI), we found no substantial heterogeneity, with I² test results of 0%. Together with a different wide range of 95% CI from individual studies, the statistical heterogeneity may have reflected some inconsistencies. Furthermore, effect estimates came from a small number of studies (only five for cMPI and three for tdMPI), thus inferred serious imprecision. However, no serious indirectness or publication bias was observed that could affect the overall results. Due to the paucity of included studies, publication bias was assessed qualitatively, and no unpublished studies were found in the literature search, suggesting that publication bias is unlikely to be a concern in this analysis. Hence, we rated the quality of evidence as moderate, as displayed in Table 3.

The seven included studies in the quantitative synthesis yielded various results in between group comparisons. Table 4.A summarizes the differences in MPI assessed by conventional echocardiography between SpA and healthy control groups. Most studies consistently reported significantly higher mean of cMPI values in patients with AS compared to healthy control, with the exception of the study by Kucuk et al., 2018, which did not demonstrate a significant difference [28]. Meanwhile, Table 4.B presented findings based on tissue Doppler echocardiography. All included studies showed that AS patients had significantly elevated tdMPI values relative to controls. For patients with uSpA, however, no statistically significant differences in MPI were observed with either echocardiographic method.

The quantitative synthesis results of AS patients for between group comparisons of MPI using conventional echocardiography were shown in Figure 2.A, whereas the results for between group comparisons of MPI using tissue Doppler echocardiography were displayed in Figure 2.B. Based on the results, significant differences of MPI using conventional and tissue Doppler echocardiography in were found in between group comparisons (MD= 0.05, 95% CI: 0.01–0.08, p-value=0.006 and MD=0.08, 95%CI: 0.06–0.10, p value<0.00001, respectively). However, the between group comparisons of MPI outcomes demonstrated high heterogeneity (I² = 87%) when assessed with conventional echocardiography, while assessments using tissue Doppler echocardiography showed low heterogeneity (I² = 0%).

Figure 2.

Meta-Analysis Results [Forest Plot] for Myocardial Performance Index in Ankylosing Spondylitis (AS) compared to healthy control; A: Conventional Myocardial Performance Index (cMPI) B: Tissue Doppler Myocardial Performance Index (tdMPI).

The cMPI demonstrated a high degree of heterogeneity, with I² results of 87%, while the tdMPI demonstrated no substantial heterogeneity, with I² results of 0%. The variability of cMPI could have stemmed from clinical, methodological, or statistical perspectives. From a clinical perspective, the differences in participants or outcomes could have led to high heterogeneity. The number of participants ranged from 30 to 59 subjects, with some studies having unequivocal male-to-female ratios. The larger the sample, the higher the likelihood of effect sizes to occur. Furthermore, the disease duration in each study was varied, with the shortest duration of at least one year and the longest duration being 19.14±7.51 years. This variability could have influenced the progression of cardiac damage, leading to more pronounced alterations in MPI values.

From a methodological perspective, the differences in population matching may have contributed to high heterogeneity. While the mean ages of the case and control groups exhibited minimal disparity, the age ranges demonstrated considerable heterogeneity, with 38±11 to 44.69±9.03 years in the case group and 36±9 to 43.58 ± 20.47 years in the control group [21,25,26]. Furthermore, ethnicity also played a crucial role in determining the diversity of SpA incidence and risk factors, considering the study population originated from different geographical regions, including Asia (Turkey) and Europe (Greece) [26]. Prior research revealed that the low prevalence of SpA coincided with a low prevalence of HLA-B27, which is predominantly found in Asia compared to other continents [43].

As the number of our included studies was fewer than 10, funnel plot assessment could have led to misinterpretation and unreliable results. Therefore, we conducted a qualitative evaluation using GRADE assessment as shown in table 3. Potential publication bias usually arose from the tendency of authors or publishers to release papers with only significant results. In this review, each study showed various significance in their reported outcomes of MPI values, as described in Table 4.A and 4.B, highlighting the fact that the studies included in our meta-analysis reported both significant and insignificant results.

To the best of our knowledge, this was the first comprehensive systematic review and meta-analysis focused on evaluating MPI in adult SpA patients. A notable strength of our study was the ability of MPI values to evaluate cardiac dysfunction in SpA using both conventional echocardiography and TDI, making the MPI evaluation widely and easily accessible. However, our study had some limitations. Although MPI was not widely utilized and was generally outperformed by other modalities for evaluating LV function, it might still have held clinical value in resource-limited settings. In such contexts, MPI could have served as a useful tool for detecting subclinical myocardial dysfunction in specific populations, such as AS patients. The number of studies was relatively small because MPI was not a routine assessment of cardiac function. This study only included observational studies, thus could not evaluate causative relations between SpA and impaired cardiac function. We also did not explore specific subsets of SpA other than AS due to paucity of studies for these specific subsets of SpA. Additionally, the findings might have been subject to geographical bias, as the majority of the included studies originated from Turkey, potentially limiting the generalizability of the findings.

Future studies might focus on clinical consequences of MPI towards cardiac dysfunction in SpA patients, and acceptable abnormal cut off for predictive and prognostic value. If its utility was proven, the MPI simplicity and durability could have made it a mainstay in clinical practice. Furthermore, comparing the effectiveness of TDI and conventional echocardiography in determining MPI accuracy might have helped determine which modality was better at identifying cardiac dysfunction in SpA.