Risk factors associated with cardiac complication after total joint arthroplasty of the hip and knee: a systematic review

This systematic literature review was performed in accordance with the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines (see Additional file 1) [26]. Prior to commencing the study, a detailed protocol was published in the PROSPERO database (registration number CRD42018095887). Four databases including Scopus, MEDLINE/PubMed, CINAHL, and the Cochrane Library were searched on 13th of May, 2018 for the following search terms: (heart OR myocard* OR cardi*) AND (arthroplasty OR “joint replacement” OR “knee replacement” OR “hip replacement”) AND (risk OR complication OR adverse OR problem OR event OR issue OR mortality OR morbidity) AND (factor* OR characteristic* OR predispos* OR predic* OR profile). The following MeSH terms were also included in our search: Arthroplasty, Cardiology, Orthopaedics, and Risk Factors. Manual searches were also performed through hand searching the reference lists of included articles.

This review included studies that explored specific risk factors for cardiac complication associated with elective primary THA and TKA in patients ≥18 years old. Studies involving other types of arthroplasty or concerning revision THA or TKA were excluded. Only studies published from 2008 onwards were considered, and studies were excluded if more than 50% of their study population were operated on prior to 2008. This review only included studies in which the indication for TJA was osteoarthritis and excluded those with fractures, inflammatory, or autoimmune disease (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis etc.). Studies examining the risk of cardiac complication associated with medication exposures, such as the use of anti-thrombotic agents and beta-blockers prior to surgery, were also excluded for the purpose of this analysis.

Cardiac complication was defined in this review as cardiac arrest (CA), myocardial infarction (MI), or new-onset arrhythmia, occurring within 90 days of THA or TKA. Articles which reported on general outcomes such as increased length of hospital stay or major complication without exploring the specific associations between a risk factor and cardiac complication were excluded. Literature that was not available in the English language, studies involving animal models, and levels IV and V evidence papers were also excluded.

Titles and abstracts were screened by two independent investigators (YE, IJ), and following exclusions, full-text articles were reviewed for eligibility. If two investigators could not reach a consensus on inclusion, a third investigator (HL) was involved in the final determination.

A quality assessment tool was specifically developed for this review based on two existing appraisal tools: the Newcastle–Ottawa Scale and the Evidence-Based Library Appraisal Checklist (Additional file 2: Table S1) [27, 28]. Our tool included 25 questions, which assessed study methodology, population selection, diagnosis, and reporting of cardiac complications, as well as the level of analysis between THA and TKA cohorts. Two authors (YE and IJ) who were blinded from study identifiers (title, author, and journal) conducted the quality assessment. Any discrepancies of two or more points led to review by a third author (HL) and discussion until consensus was achieved. All 25 questions were equally weighted and individual scores were calculated based on the number of ‘YES’ answers. The final score was calculated as a percentage of the number of answerable questions. Studies that scored < 80%, 80–89%, and > 90% were deemed of low, moderate, and high quality, respectively.

The systematic search identified 2544 articles (Fig. 1). Following removal of duplicates, 1809 articles remained for screening. The majority of articles were excluded for arthroplasty other than primary THA or TKA (revision, shoulder, ankle, or elbow arthroplasty), indications other than osteoarthritis, and studies primarily concerned with infection or thrombo-embolic disease. Sixty-seven full-text articles were evaluated; 33 were excluded because they did not report any association between risk factors and cardiac complication, 9 included arthroplasties other than primary TJA for osteoarthritis, 4 in which > 50% of surgeries occurred prior to 2008, 3 for lack of specific risk factor analysis, and 3 for follow-up times beyond 90 days and population age outside of the inclusion range (Fig. 1). A total of 15 articles were eligible for inclusion in this systematic review, with a publication range from 2014 to 2018.

All studies included in this series were retrospective in nature (Table 1) with the exception of Abdel et al., which utilised a prospective design [29]. Fourteen studies were classified as level III evidence, reflecting the majority of cohort studies, whilst one was level II [29]. Many of the studies derived their study population from shared databases, such as the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database, National Inpatient Sample (NIS), Medicare in-patient claims data, and other joint registries. A total of 8 of 15 articles included both THA and TKA study populations, 6 used TKA cohorts and 1 used THA (Table 1). Five studies included only unilateral TJA, three included both unilateral and bilateral procedures, and seven studies did not specify between unilateral and bilateral procedures.

Seven studies followed patients for 30 days after TJA, four included a 90-day postoperative follow-up period, and four only reported in-hospital complications (Table 1). MI was assessed by 14 studies, CA in 7, and arrhythmia in only 2. Authors in one study [30] did not specify which cardiac complication they evaluated. Risk factors evaluated by the included studies included modifiable and non-modifiable patient factors, comorbidities, and surgery type (Table 1).

Across the 15 studies, study populations ranging in age between 18 and > 85 years old were included; most studies reported an average age of mid-to-late 60s (Table 2). The total number of study participants cannot be accurately identified due to a high likelihood of duplicate study populations. In 13 studies, TJA cohorts were predominated by the female gender (Table 2), whilst two studies did not provide gender-specific information of the total cohort in their primary text [5, 31]. The most common arthroplasty procedure in this series was TKA, with the exception of two studies [17, 30].

The inter-observer agreement on the quality of included studies ranged between 90 and 100%. Out of 15 articles included in this review, only 2 were deemed high quality, 11 were moderate quality, and 2 were low quality according to the appraisal tool used (Additional file 2: Table S1). Study quality was mainly limited by the use of study populations derived from large shared databases, the lack of specificity surrounding TJA details (indication, unilateral vs. bilateral), and failure to discuss definitions of the studied cardiac complication in relation to an accepted guideline.

The incidence of cardiac complication ranged from 0.07 to 3.0% across the studies [4, 7]. Several comorbidities were investigated for an association with cardiac complication in THA and TKA. Age, gender, type of arthroplasty, history of cardiac disease, hypertension, chronic pulmonary disease, diabetes, and obesity were thoroughly evaluated in our series (Table 3). Other risk factors including renal failure, malnutrition, anaemia, alcohol abuse, cerebrovascular disease, and smoking history were discussed, though reported to a lesser extent (Table 3).

Six studies reported on the relationship between age and cardiac complication (Additional file 3: Table S2) [4, 5, 7, 8, 11, 12]. For age ≥ 80 years, both Waterman et al. and Belmont Jr. et al. reported increased odds of cardiac complication in both TKA (OR 1.85; 95% CI 1.23–2.79; p = 0.003 and OR 27.95; CI 95% 2.01–388.93; p = 0.0016, respectively) and THA (OR 4.39; 95% CI 2.29–6.61; p < 0.001 and OR 3.72; CI 95% 1.53–9.06; p = 0.0001, respectively) [5, 12]. Menendez et al. similarly reported an increased risk for patients aged 45–64 (OR 4.4; CI 95% 2.6–7.4; p < 0.001), 65–84 (OR 6.5; CI 95% 3.8–11.0; p < 0.001), and > 85 (OR 9.4; CI 95% 5.5–16.1; p < 0.001) [11]. Conversely, Feng et al. did not show any association between age and cardiac complication (Additional file 3: Table S2) [4].

The influence of gender on the risk of cardiac complication in TJA was also assessed in six studies (Additional file 3: Table S2) [4‐8, 11]. Robinson et al. found that female gender was a protective factor for myocardial infarction in both THA (OR 0.54; 95% CI 0.40–0.75; p < 0.001) and TKA (OR 0.59; 95% CI 0.45–0.76; p < 0.001) [6]. In contrast, male gender was associated with increased risk of MI in THA (OR 1.84; 95% Cl 1.34–2.52; p < 0.001) and TKA (OR 1.71; 95% Cl 1.31–2.22; p < 0.001). Menendez et al. noted similar findings for male gender as a risk (OR 1.4; CI 95% 1.4–1.5; p < 0.001) [11]. Feng et al., Shah et al., and Belmont Jr. et al. did not find a statistically significant predictive value of gender for cardiac complication post-TJA (Additional file 3: Table S2) [4, 5, 7].

Seven articles explored the relationship between a history of cardiac disease and post-operative cardiac complication [4, 5, 7, 8, 12, 32], with all seven reporting a positive association (Additional file 4: Table S3). The strongest association was shown by Feng et al. who found that a history of MI was associated with a significantly increased odds ratio for cardiac complication following TJA (15.1, 95% Cl 4.1–56.3; p < 0.001) [4]. Congestive heart failure and coronary artery disease were found to be predictive risk factors for cardiac complication in two studies [11, 32], with the study by Menendez et al. also identifying an association with peripheral vascular and valvular disease (Additional file 4: Table S3) [11].

Of 15 articles in this series, 8 investigated the effect of obesity on cardiac complication post-TJA (Additional file 4: Table S3) [4, 7, 8, 17, 29, 30, 33, 34]. Feng et al. reported that study participants with BMI ≥ 30 were at greater risk of cardiac complication (OR 2.477; Cl 95% 1.17–5.21; p = 0.017) [4]. None of the other seven studies demonstrated a statistically significant relationship between obesity and cardiac complication associated with THA and TKA (p > 0.05). Conversely, Anoushiravani et al. and Thornqvist et al. suggested a possible relationship between underweight patients undergoing TJA and cardiac complication; however, a p value was not reported (Additional file 4: Table S3) [8, 30].

The effect of hypertension on risk of cardiac complication was analysed in four studies (Additional file 3: Table S2) [5, 7, 11, 12]. Belmont Jr. et al. reported statistically significant associations for both TKA (OR 4.74; CI 95% 1.04–21.59; p = 0.044) and THA (OR 2.59; CI 95% 1.07–6.23; p = 0.0341) [5]. Similar findings were demonstrated by Waterman et al. for TKA (OR 2.14; 95% CI 1.30–3.52; p = 0.003) and THA (OR 1.82; 95% CI 1.09–3.03; p = 0.02) [12]. In contrast, Menendez et al. found that hypertension was not associated with increased risk of cardiac complication (OR 0.9; CI 95% 0.8–1.0; p = 0.003) [11], whilst Shah et al. similarly found no effect for this risk factor (Additional file 3: Table S2) [7].

Four studies examined an association between diabetes and cardiac complication (Additional file 3: Table S2) [5, 7, 8, 11]. Belmont Jr. et al. found that for TKA, diabetes was positively associated with post-operative cardiac complications (OR 2.62; CI 95% 1.41–4.87; p = 0.0023); however, the results were not significant for THA [5]. Menendez et al. discussed cardiac complication in relation to complicated and uncomplicated diabetes, with both shown to be associated (OR 1.1; CI 95% 1.1–1.2; p < 0.001 and OR 1.2; CI 95% 1.0–1.3; p < 0.04, respectively) [11]. No relationship between diabetes and cardiac complication was found by Shah et al. (Additional file 3: Table S2) [7].

Differences between THA and TKA in relation to cardiac complication were examined in four of the studies (Additional file 3: Table S2) [4, 7, 8, 11]. In comparison to TKA, Menendez et al. showed that THA was a better predictor for post-operative cardiac complication (OR 1.3; CI 95% 1.3–1.4; p < 0.001) [11]. Shah et al. found increased risk of MI and CA in both THA and TKA populations compared with knee arthroscopy controls (OR 2.61; CI 95% 1.46–4.69; p = 0.001 and OR 1.98; CI 95% 1.08–3.62; p = 0.03, respectively) (Additional file 3: Table S2) [7].

Feng et al. found no difference in cardiac complication risk for TKA and THA, although the authors did identify simultaneous bilateral procedures as a greater predictor of cardiac events than unilateral arthroplasty (OR 1.57; Cl 95% 1.074–2.294; p = 0.02) (Additional file 4: Table S3) [4]. Whilst one study reported an odds ratio of 1.1 (CI 95% 1.0–1.2; p < 0.006) for the association between renal failure and cardiac complication [11], Shah et al. and Belmont Jr. et al. found no significant association (Additional file 3: Table S2) [5, 7]. Four studies examined the effect of cerebrovascular disease; however, only two studies demonstrated statistically significant results [5, 7, 8, 11]. Menendez et al. and Belmont Jr. et al. concluded that cerebrovascular disease increased the risk of post-TJA cardiac complication (OR 2.3; CI 95%, 2.0–2.6; p < 0.001 and OR 2.20; CI 95% 1.02–4.75; p = 0.0441 [THA population], respectively) (Additional file 4: Table S3). Four studies also examined chronic pulmonary disease as a risk factor for cardiac complication [5, 7, 8, 11]. Menendez et al. reported an odds ratio of 0.8 (CI 95% 0.7–0.8; p < 0.001) for an acute MI, whereas Shah et al. and Belmont et al. did not show an association (Additional file 3: Table S2). Malnutrition, defined as an albumin level < 3.5 g/dL, and adjusted for BMI, was associated with greater risk of cardiac complication in the study by Fu et al. (OR 2.23; CI 95% 1.21–4.12; p = 0.010) [33]. Out of three studies examining anaemia and cardiac complication, only Menendez et al. showed statistical significance (OR 1.4; CI 95% 1.3–1.5; p < 0.001) [5, 11, 35]. Smoking history was only examined by Shah et al. who found a significant association with cardiac complication in a THA population (OR 2.56; CI 95% 1.34–4.91; p = 0.005) [7]. Finally, of the two studies that employed the American Society of Anesthesiologists (ASA) scoring system, only Shah et al. demonstrated an association [5, 7]. In their analysis of the effect of ASA 3 to 4 in both THA and TKA, only the TKA population was significantly predictive of cardiac complication (OR 2.47; CI 95% 1.28–4.74; p = 0.007) [7].