SYSTEMATIC REVIEW published: 25 March 2022 doi: 10.3389/fmed.2022.851483 Prevalence and Risk for Bundle Branch Block, Atrioventricular Block and Pacemaker Implantation in Spondyloarthritis. A Systematic Review of the Literature Hye Sang Park 1,2 , Ana Laiz 2,3 , Petra Díaz del Campo 4 , María A. Martín Martínez 4,5 , M. Guerra-Rodriguez 4 , Concepcion Alonso-Martin 5 , Jesus Sanchez-Vega 6 and Hector Corominas 1,2,3* 1 Department of Rheumatology, Hospital Dos de Maig, Barcelona, Spain, 2 Department of Rheumatology and Autoimmune Diseases, Hospital Universitari de la Santa Creu i Sant Pau, Barcelona, Spain, 3 Department of Medicine, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain, 4 Unidad de Investigación, Spanish Society of Rheumatology, Madrid, Spain, 5 Department of Cardiology, Hospital Universitari de la Santa Creu i Sant Pau, Barcelona, Spain, 6 Department of Cardiology, Hospital Universitari Bellvitge, Hospitalet de Llobregat, Universitat de Barcelona (UB), Barcelona, Spain Edited by: Clementina López-Medina, Objective:To evaluate the evidence regarding the prevalence and risk of bundle branch Reina Sofía Hospital, Spain block (BBB), atrioventricular block (AVB) and pacemaker implantation (PMI) in patients Reviewed by: with spondyloarthritis compared to a control group without spondyloarthritis. Michael T. Nurmohamed, VU Medical Center, Netherlands Methods: A systematic review of the literature was performed using Pubmed (Medline), Julianna Desmarais, Oregon Health and Science University, EMBASE (Elsevier) and Cochrane Library (Wiley) databases until December 2021. The United States prevalence and risk for AVB, BBB and PMI were analyzed. Cohort, case control and *Correspondence: cross-sectional studies in patients ≥18 years meeting the classification criteria for Hector Corominas spondyloarthritis were included. The Odds ratio (OR), risk ratio (RR), or Hazard ratio hcorominas@santpau.cat (HR) and prevalence difference were considered as outcomes. Data was synthesized Specialty section: in a previously defined extraction form which included a risk of bias assessment using This article was submitted to the Newcastle-Ottawa Scale. Rheumatology, a section of the journal Results: In total, eight out of 374 studies were included. None of the studies Frontiers in Medicine provided results regarding the risk of low grade AVB and BBB in SpA patients. Only Received: 09 January 2022 indirect results comparing prevalences from low to medium quality studies were found. Accepted: 16 February 2022 Published: 25 March 2022 According to population based registries, the sex and age adjusted HR of AVB was 2.3 Citation: (95% CI 1.6–3.3) in ankylosing spondylitis, 2.9 (95% CI 1.8–4.7) in undifferentiated Park HS, Laiz A, Díaz del Campo P, spondyloarthritis and 1.5 (95% CI 1.1 a 1.9) in psoriatic arthritis. The absolute risk for AVB Martín Martínez MA, Guerra-Rodriguez M, was 0.4% (moderate to high; 95% CI 0.34%-0.69%) for AS, 0.33% (moderate to high; Alonso-Martin C, Sanchez-Vega J and 95% CI 0.21%-0.53%) for uSpA and 0.34% (moderate to high; 95% CI 0.26%-0.45%) for Corominas H (2022) Prevalence and PsA.The RR for PMI in AS patients was 1.3 (95% CI 1.16–1.46) for groups aged between Risk for Bundle Branch Block, Atrioventricular Block and Pacemaker 65 and 69 years, 1.33 (95% CI 1.22–1.44) for 70–75 years, 1.24 (95% CI 1.55–1.33) for Implantation in Spondyloarthritis. A 75–79 years and 1.11 (95% CI 1.06–1.17) for groups older than 80 years. The absolute Systematic Review of the Literature. Front. Med. 9:851483. risk for PMI in AS patients was 0.7% (moderate to high risk; 95% CI 0.6–0.8%) for groups doi: 10.3389/fmed.2022.851483 aged between 65–69, 1.44% (high risk; 95% CI 1.33–1.6%) for 70–75 years, 2.09% Frontiers in Medicine | www.frontiersin.org 1 March 2022 | Volume 9 | Article 851483 Park et al. Heart Block in Spondyloarthritis (high risk; 95% CI 2.0–2.2%) for 75–79 years and 4.15% (high risk; 95% CI 4.0–4.3%) for groups older than 80 years Conclusions: Very few cases of low grade AVB and BBB were observed in observational studies. No study evaluated association measures for low grade AVB and BBB but the differences of prevalence were similar in SpA and control groups even though studies lacked the power to detect statistical differences. According to population based registries there was an approximately two fold-increased risk of high grade AVB in SpA patients. RR for PMI was higher in younger age groups. Keywords: spondylarthritis, spondyloarthritis, cardiac conduction system disease, pacemaker, epidemiology, systematic review INTRODUCTION The aim of this systematic review of the literature is to evaluate the prevalence and risk of bundle branch block (BBB), Over the last 100 years, cardiac vasculature, valves, myocardium, atrioventricular block (AVB) and pacemaker implantation (PM) pericardium, and conduction system disorders were observed in patients with spondyloarthritis compared to a control group in inflammatory rheumatic disease. The cardiac diseases without spondyloarthritis. most commonly described were cardiovascular ischaemic events, valve diseases, ventricular dysfunction and conduction disorders (1). The common hypothesis is that systemic MATERIALS AND METHODS inflammation accelerates tissue degeneration which in turn causes cardiovascular diseases. Nevertheless, it is unknown A systematic review was conducted to identify all studies whether the different inflammatory rheumatic diseases have published up to December, 2021. This review was guided by tropism for a specific cardiac structure or tissue (1). the preferred reporting items for systematic review and meta- The aortic valve attachment site and peripheral entheses are analysis (PRISMA) statements (Supplementary Table 1). known to share histological similarities (2). Two experimental studies observed that enthesis tissue resident T cells were also Research Question present in the aortic root and valve while being absent from the The research question was defined using PICO myocardium. Overexpression of interleukin-23 in vivo resulted (Population, Intervention, Comparison, Outcome and Study in a dense infiltrate of T cells, macrophages and neutrophils in design) components. the attachment site of the aortic valve leading to the aortic wall, Are patients ≥ 18 years who have spondyloarthritis as well as in the enthesis (3, 4). According to those findings, at an increased risk or higher prevalence for AVB, BBB inflammation of the valve attachment site may produce tissue and PMI compared with a control group that do not degeneration near the atrioventricular node, which may lead have spondyloarthritis? to electrical conduction disturbancesdistrubances, that is to say atrioventricular block (AVB) and bundle branch block (BBB). Inclusion Criteria Among a sea of similar information, it is necessary to critically We included studies that met the following requirements: review the available evidence up-to-date and acknowledge the downsides to guide further investigation of each of the cardiac • Study population: patients older than 18 years, diagnosed as manifestations and inflammatory rheumatic diseases. We have Spondyloarthritis disease classified by ASAS, ESSG, Amor, previously carried out a systematic review of the literature of modified New York, ARA, Moll & Wright or CASPAR the prevalence and risk of heart valve and aortic involvement in criteria. Also patients diagnosed with spondyloarthritis spondyloarthritis (SpA) (5). Higher risk for valvular heart disease following International Classification of Diseases (ICD) was observed in SpA patients and a with an approximately HR codes, or with a diagnosis confirmed by grade II bilateral 1.97 adjusted by confounders and RR of 1.2. A a smallsmall sacroiliitis or grade III or superior if unilateral sacroiliitis increase was observed for aortic valve procedures RR 1.1–1.3 was identified by X-Ray; and/or HLAB27 positivity; and but not for mitral valve. Most studies were not adjusted by fulfilling two or more clinical characteristics (peripheral potential confounders. arthritis, enthesitis, dactylitis, uveitis, inflammatory back pain, psoriasis, inflammatory bowel disease, history of urethritis or infective diarrhea) were included. Abbreviations: AS, Ankylosing Spondylitis; AVB, Atrioventricular Block BBB, • Intervention: studies containing information about Bundle Branch Block; BMI, Body Mass Index; ECG, Electrocardiogram ICD, atrioventricular block, left and right bundle branch block International Classifica IR, Incidence Rate HR, Hazard Ratio LBBB, Left Bundle Branch Block PM, Pacemaker OR, Odds Ratio; ReA, Reactive arthritis; POR, measured by electrocardiogram (ECG) or holter. Prevalence Odds Ratio PsA, Psoriatic Arthritis; RBBB, Right Bundle Branch Block • Outcome variables: studies containing information about RR, Risk Ratio SpA, spondyloarthritis; uSpA, undifferentiated spondyloarthritis. association measures such as incidence ratio (IR), odds ratio Frontiers in Medicine | www.frontiersin.org 2 March 2022 | Volume 9 | Article 851483 Park et al. Heart Block in Spondyloarthritis (OR), risk ratio (RR) and Hazard Ratio (HR) and comparison Risk of Bias of prevalences. The risk of bias was assessed by two reviewers (HSP & AL) using • Study design: Systematic review of the literature, meta- the Newcastle-Ottawa Scale (NOS) for assessing the quality of analysis, case control, cohort, cross sectional studies with more nonrandomized studies. The NOS contains eight items with an than 100 patients or population based registries. overall minimum score of one and a maximum of nine stars. • Language: English, French, Korean and Spanish. There are three main quality dimensions: (1) selection of the study population; (2) comparability between the groups; and (3) outcome or exposure measures for cohort and case– control Exclusion Criteria studies, respectively. The overall scores given were categorized Studies carried out on pregnant women, animals or ethnic into high (8–9 stars), medium (6–7 stars) and low quality minorities. Abstracts, posters, narrative reviews, letters, editorials (≤5 stars). We also categorized studies according to exposure and any type of unpublished study. assessment quality into high (three stars), medium (two stars) and low quality (one star). The complete checklist used is Search Strategy included in the Supplementary Material. A systematic search strategy was performed using the databases of Pubmed (Medline), EMBASE (Elsevier) and the Cochrane RESULTS Library (Wiley) by a librarian (MG). The search strategy included MeSH terms and free text using different combinations Study Selection (Supplementary Figure 1). Additional references were manually We selected 62 studies of the original 374 studies for further retrieved by reviewing the references of the included studies. reading based on title and abstract screening. After excluding 53 Four studies were not available mainly because of antiquity studies following full text reading, we included eight studies in (Supplementary Figure 2). They were previously consulted the analysis, as presented in the PRISMA flow-chart (Figure 1). in two different national university library sources and the The reasons for excluding the remaining studies after reading the documentary collection of the Spanish Society of Rheumatology. full text are provided in Supplementary Figure 3. No additional An update of the systematic research was performed in December study was retrieved after reviewing the bibliography of the articles 2021 before the submission of this manuscript. included for a full text reading. The final selection included two population based cohort studies, two case control studies and four cross-sectional studies. Article Selection A total of 373 citations were peer reviewed by two Characteristics of the Selected Studies rheumatologists (HSP & AL). The reviewers independently Detailed information regarding study design, location, sample performed two-stage screening (title/abstract and full-text size, follow up duration, exclusion and inclusion criteria, the screening), data extraction, and a risk of bias assessment. methodology applied for the assessment of conduction disorder EndNote X8 software was used to manage the literature and outcome measures is summarized (Table 1). references. Those articles that were not considered relevant for further checking were excluded and the reason for exclusion Baseline Characteristics of the were listed (Supplementary Figure 3). Senior methodologists (PDC & MAM) and a cardiac electrophysiologist (CAM & JSV) Participants Mean age at enrollment was 33–54 years in five of the eight were consulted to retrieve clinically relevant data and for the studies. Three studies were based on a specific age population: interpretation of the results. one study was based on patients between 50 and 75 years old (6), one study was based on patients older than 65 of age (12) and Data Extraction and Data Analysis another study was based on patients between 18 and 50 of age For data extraction, a previously designed form in Word R (10). The proportion of women ranged from 8 to 72% depending format was used. Data collected from each study were: country on the type of spondyloarthritis. Mean disease duration was 3.9– of study, design, sample size, participant selection, period of 22 years (6, 8, 9, 13). Hypertension was observed in 24.1–66% recruitment, follow-up period, method applied for conduction of patients (6–8, 11). Ischaemic heart disease was observed in disorder diagnosis, magnitude of association and confounder 7.3–9% (6, 7, 9). Mean BASDAI was 3.1–5.9 (6, 8, 11). Uveitis factors. Prevalence odds ratio (POR), OR or comparison of was observed in 1.6–20.8% (7, 11, 13) depending on the type proportions were calculated with the information available if of spondyloarthritis. necessary. Data was extracted by one reviewer (HSP) and supervised by another reviewer (AL). Disagreements between Risk of Bias Assessment the reviewers were solved by discussion. When there was no Four longitudinal observational studies were evaluated using the consensus a third reviewer was consulted (PDC or CAM). NOS scale (Table 2). One was of medium quality (13), another After gathering information, a narrative synthesis was was of low quality (9) as the other two studies were of high preferred over a meta-analysis due to heterogeneity in quality. One study showed a possible selection bias as eligibility population, design and/or the outcome measure of the was not clearly described (9). All studies were matched or included studies. adjusted by sex and age but none evaluated possible confounding Frontiers in Medicine | www.frontiersin.org 3 March 2022 | Volume 9 | Article 851483 Park et al. Heart Block in Spondyloarthritis FIGURE 1 | PRISMA flow chart. factors. Only one study also adjusted for race (12). Two studies with RBBB was 0 and 4.1% (p = 1.0), and 0 and 2.7% for groups did not provide information about loss to follow-up (12) or with LBBB (p = 0.1). In all studies the comparison of prevalence nonresponse rate (9). or the OR were neither clinically nor statistically significant. None of the four cross sectional studies evaluated possible confounding factors. The statistical method was not clearly described in two studies (8, 11). Atrioventricular Block Only one study provided information regarding the risk of high Description and Analysis of the Results grade AVB in SpA (7). Three studies compared the prevalence of Five studies reported data regarding the risk of spondyloarthritis low and high grade AVB in SpA and control groups (6, 9, 11, 13). for bundle branch block, atrioventricular block or When using (6, 9, 11) ECG the prevalence of SpA patients pacemaker implantation when compared to the population with 1st degree AVB was 1–2.8% and no case of 2nd/3rd degree without spondyloarthritis. AVB was observed in any of the studies. No case of AVB was observed in the control groups. In all studies the comparison of Bundle Branch Block the prevalence or the OR were neither clinically nor statistically No studies provided information regarding the risk of BBB in significant (p = 1.0). patients with SpA. Three studies compared the prevalence of BBB When using a Holter monitor, transient cases of AVB were between SpA patients and control groups (6, 11, 13). observed (13). The prevalence of SpA patients with 1st degree Only one or two cases of RBBB and LBBB were observed in the AVB was 3.41%, that of Mobitz II 2nd degree AVB was 1.13% SpA group of each of the studies. The proportion of SpA patients and that of asymptomatic 3rd degree AVB was 1.13%. Only one with RBBB was between 0.9% and 1.14%, and the proportion of person from control group had transient Mobitz I 2nd degree LBBB was between 1 and 2.7%. The proportion of control groups AVB but none other type of AVB was observed. Once again, Frontiers in Medicine | www.frontiersin.org 4 March 2022 | Volume 9 | Article 851483 Park et al. Heart Block in Spondyloarthritis TABLE 1 | Characteristics of the selected studies. References Study design Population Sample number Follow up Test Outcomes Adjustment Baniaamam et al. (6) Cross sectional AS and osteoarthritis 267 - ECG Prevalence of AVB, Controls matched between 50 and 75 BBB and PMI for age, sex and years smoking status Bengtsson et al. (7) Cohort AS, uSpA, PsA, GP 294136 7 years (1st Jan ICD-10 Prevalence, Age, sex from the Swedish 2006–31st Dec 2012) Incidence, HR, for national registry AVB and PMI compared to GP Dik et al. (8) Cross sectional AS 131 - ECG Prevalence of AVB Age, sex, disease and BBB duration Association of PR interval with AS disease related variables Feld et al. (9) Case control PsA compared to non 184 Average 7.5 years (no ECG Prevalence of AVB, None psoriatic nor arthritic further information) BBB patients Correlation of PR interval with AS disease related variables Fu et al. (10) Cross sectional AS between 18 and 122 - ECG Prevalence of AVB, None 50y without cardiac BBB disease AS without kyphosis Goulenok et al. (11) Cross sectional SpA, RA and control 288 - ECG Prevalence AVB, BB None group without known CV disease Ward (12) Cohort AS from Medicare 42,327 14 years (1999–2013) ICD-9 Prevalence, Age, sex, race database older than 65 incidence, OR of PMI Yildrir et al. (13) Case control AS 88 Holter and ECG Prevalence of AVB None TABLE 2 | Risk of bias assessment of the cohort and case control studies. reported[|2]. The incidence (1,000 person-years) was 0.86 in AS, 0.61 in uSpA and 0.6 in PsA. The IR was 2.0 (95% CI 1.3–2.7) in References Selection Comparability Outcome/Exposure Quality AS, 1.5 (95% CI 0.7–2.2) in uSpA and 1.5 (95% CI 1.2–1.8) for Bengtsson et al. 4 1 3 HIGH PsA. The absolute risk for AVB was 0.4% (moderate to high; 95% (7) CI 0.34–0.69%) for AS, 0.33% (moderate to high; 95% CI 0.21– Feld et al. (9) 2 1 2 LOW 0.53%) for uSpA and 0.34% (moderate to high; 95% CI 0.26– Ward (12) 4 2 2 HIGH 0.45%) for PsA. The sex and age adjusted HR was 2.0 (95% CI Yildrir et al. (13) 3 1 3 MEDIUM 1.6–2.8) in AS, 1.9 (95% CI 1.2–2.8) in uSpA and 1.6 (95% CI 1.3–1.9) for PsA. Incidence, absolute risk, OR and RR adjusted for sex and race were reported in an American AS population older than 65 the differences in prevalence and OR were neither clinically nor years of age stratified by age intervals (12). The incidence (1,000 statistically significant (p = 0.56). person-years) was 3.59 (95% CI 3.26–4.10) for the group aged The risk of high grade AVB (2nd and 3rd degree) was between 65 and 69 years, 6.68 (95% CI 6.28–7.36) for the 70– evaluated using ICD-9 codes by a population based registry (7). 75 group, 10.04 (CI 95% 9.66–11.04) for the 75–79 group, 14.6 The sex and age adjusted IR of AVB was 0.9 (95% CI 0.6–1.3) in (95% CI 14.21–15.61) for groups older than 80 years of age. The AS, 1.2 (95% CI 0.5–1.9) in uSpA and 0.7 (95% CI 0.5–0.9) in absolute risk for PMI in AS patients was 0.7% (moderate to high PsA. The sex and age adjusted HR of AVB was 2.3 (95% CI 1.6– risk; 95% CI 0.6–0.8%) for groups aged between 65 and 69, 1.44% 3.3) in AS, 2.9 (95% CI 1.8–4.7) in uSpA and 1.5 (95% CI 1.1 a (high risk; 95% CI 1.33–1.6%) for 70–75 years, 2.09% (high risk; 1.9) in PsA. 95% CI 2.0–2.2%) for 75–79 years and 4.15% (high risk; 95% CI 4.0–4.3%) for groups older than 80 years. The OR was 1.38 (95% Pacemaker Implantation CI 0.97–1.96) for the group aged 65–69 years, 1.28 (95% CI 0.82– Two population based registries evaluated the risk of pacemaker 1.67) for the 70–75 group, 1.18 (95% CI 0.94–1.48) for the 75–79 implantation in spondyloarthritis compared to a control group. group, and 1.23 (95% CI 1.1–1.39) for the group older than 80 The incidence, absolute risk, IR (1,000 person-years) and years of age. The RR was 1.3 (95% CI 1.16–1.46) for the group HR adjusted for age and sex in the Swedish population were aged between 65 and 69 years, 1.33 (95% CI 1.22–1.44) for the Frontiers in Medicine | www.frontiersin.org 5 March 2022 | Volume 9 | Article 851483 Park et al. Heart Block in Spondyloarthritis 70–75 group, 1.24 (95% CI 1.55–1.33) for the 75–79 group and low prevalence of BBB in the young population under 65. Also 1.11 (95% CI 1.06–1.17) for the group older than 80 years of age. important information that may have shed some light on, such as The causes for PMI were sinoatrial dysfunction in 41.8%, AVB in cardiovascular risk factors, cardiac disease, drugs and SpA disease 16.6% and atrial fibrillation in 7.6%. related characteristics were missing. Spondyloarthritis Related Prognostic Factors Associated to Conduction AVB and PM Disorders First degree, Mobitz I and transient AVB are asymptomatic Even though it was not the main objective of this systematic and benign so they may not be detected if not sought. The review, we synthesized the data retrieved on SpA disease related prevalence of low degree AVB increases at older age (16, 17) prognostic factors for AVB or BBB. Three studies evaluated and may progress over time to a higher grade AVB. The overall indirect association (8–10). prevalence for low grade and transient AVB was around 1–3%, Two studies evaluated AVB by studying the possible The prevalence of low grade AVB was similar in control groups association between the clinical factors of SpA and PR interval according to two case control studies. Once again, due to the duration (8, 9). PR interval duration was associated with age (B scarce number of cases, small sample size and lack of confounder = 0.6, p = 0.001), disease duration (B = 0.75, p ≤ 0.001) and BMI analysis, the results do not allow us to draw conclusions about (B = 1.23, p = 0.016) by univariate analysis (8). Age and disease the risk of SpA for low grade AVB. It would be of interest to duration was statistically significant by multivariate analysis but evaluate if SpA patients present AVB at a younger age and detect no further data was provided. On the contrary another study did progression to a higher grade AVB through a longitudinal cohort not find any correlation with disease duration, subtype of PsA or study with a long follow-up. uveitis but the authors concluded that the sample size was too In contrast, high grade AVB (Mobitz II or 3rd degree) (16) is a small to detect possible associations (9). potentially life-threatening conduction disease that may lead to a The prevalence of RBBB was similar in AS patients between cardiac arrest. High grade AVB usually requires hospitalization 18 and 50 years of age with and without kyphosis due to more for PM implantation (18). Thus a population based registry evolved disease (10). In patients with kyphosis 3 (5.3%) cases based on discharge information would adequately reflect the real of RBBB were observed while in patients without kyphosis four incidence and risk of high grade AVB if adjusted for appropriate cases (6.2%) were observed. The differences in prevalences were confounders. According to the results of this systematic review, neither clinically nor statistically significant (p = 0.86). there is a two-fold increase in the risk of high grade AVB in the SpA population compared to the control population according to a population based registry (7). Accordingly, the same study DISCUSSION also observed a two-fold increase in the risk of PM in the SpA Summary of the Main Findings population compared to the control population (7). The main findings of this systematic review showed that there are Another registry based on population older than 65 years of no significant differences in prevalences of BBB and low grade age (12) did not observe a relevant risk of PMI (RR between AVB in SpA patients when compared to a control group. The 1.1 and 1.3) compared to the control population. Interestingly, risk of high grade AVB and PMI was approximately double- this study also showed a decreasing risk in higher age intervals fold increased in all types of SpA adjusted for sex and age practically matching the control population in populations older according to a population based registry. The risk of PMI in AS than 80 years of age. High grade AVB and PM implantation are population older than 65 years was smaller lower according to conditions that occur in older age. According to these studies, another population based registry possibly because PMI risk is it may be speculated that in SpA patients high grade AVB increased in older populations. The RR was about 1.3 but showed and PM implantation occur at younger ages. However when a decreasing tendency with older age intervals adjusted for sex compared to a longitudinal cohort study conducted in a hospital and race. setting, population registry sources lack clinical follow-up information which is essential to study confounders. Results must BBB be adjusted for drugs, cardiovascular risk factors or previous Isolated BBB is a conduction delay that does not require cardiac diseases. treatment in itself (14). The prevalence of BBB is difficult to estimate because it is frequently underdiagnosed in asymptomatic patients. In the Framingham study (15) the SpA Related Prognostic Factors for prevalence of BBB was between 0.5 and 1% in subjects under 50 Conduction Disorders years of age but prevalence was almost 11% in subjects between As for possible SpA related prognostic factors for conduction 80 and 90 years of age. disorders, only one study provided some relevant information. In this systematic review, no study that evaluated risk of BBB However, this study evaluated indirect outcome measures using in SpA was found. Two cross sectional and case control studies the PR interval. The PR interval was associated with age and provided indirect evidence that compared prevalence in SpA disease duration when adjusted for in a multiple regression (8). group and control group. Very few cases were observed in each Other studies were not adjusted and had a very small number group. The sample sizes were not adequate for evaluating the of cases. Frontiers in Medicine | www.frontiersin.org 6 March 2022 | Volume 9 | Article 851483 Park et al. Heart Block in Spondyloarthritis Strength and Limitations The results obtained in our review give rise to many This systematic review aimed to verify and challenge rooted questions that remain to be answered. We suggest that future concepts using an exhaustive bibliographic search of the existing research into on conduction disorder in SpA should look literature without time limit. This is the first systematic review deeper into the influence of age and identify which are the of the literature to evaluate the prevalences and risk of AVB, prognostic factors. Further studies must analyze the severity BBB, and PMI in SpA. Meta-analysis was not carried out due of conduction disorders and evaluate the influence of obesity, to the heterogeneity of the population, design, diagnostic test cardiovascular risk factors and medication in collaboration and outcome measures of the few studies retrieved. Indirect with cardiologists. From then on studies may evaluate the outcomes were reported such as comparisons of prevalence usefulness of screening (ECG, Holter monitor or even wearable with the aim of being as comprehensive as possible given the devices) for early detection of conduction disorders in patients information provided even though most studies lacked sufficient that are at higher risk. the, the progression of low grade to statistical power. higher grade AVB and screening with and identify possible prognostic factors. CONCLUSIONS DATA AVAILABILITY STATEMENT None of the studies provided results about the risk of low grade AVB and BBB in SpA patients. Indirect results comparing The original contributions presented in the study are included prevalence from low to medium quality studies were found. in the article/Supplementary Material, further inquiries can be These studies conclude that there was no difference in prevalence directed to the corresponding author. of low grade AVB and BBB in SpA patients when compared to control groups. According to population based registries, a higher AUTHOR CONTRIBUTIONS risk of high degree AVB and PM implantation in younger aged SpA patients compared to control groups when adjusted by age MG-R performed the systematic literature search. HP and AL and sex. However these results were not adjusted by clinically were involved in data screening, extraction, analysis and drafted relevant confounders. the manuscript. PD, HC, and MM contributed substantially to The majority of the studies that evaluate the association the study conceptions, design and critical revision of the article. between cardiac diseases and inflammatory rheumatic diseases JS-V and CA-M were consulted for interpretation of the extracted are small scaled observational studies or population based data as referent cardiologists. All authors read and approved the registries. Small scaled studies may not have sufficient power final manuscript. to detect differences of an infrequent manifestation but may find small subclinical changes in an asymptomatic stage. Population based registries may be useful for studying infrequent ACKNOWLEDGMENTS manifestations but lack clinically relevant information to adjust We thank David Bridgewater and David Moore for the English for confounders. Prospective cohort studies with long follow- editing of the article. up are the most accurate design, as for example, the CARMA project (19) for cardiovascular mortality. However this kind of study is rare due to the considerable research effort and budget SUPPLEMENTARY MATERIAL needed. Among a sea of similar information, it is necessary to critically review the available evidence to date and acknowledge The Supplementary Material for this article can be found the downsides to guide further investigation of each of the cardiac online at: https://www.frontiersin.org/articles/10.3389/fmed. manifestations and inflammatory rheumatic diseases. 2022.851483/full#supplementary-material REFERENCES 5. Park HS, Laiz A, Sanchez-Vega J, Díaz Del Campo, P, Martín-Martínez MA, et al., Valve abnormalities, risk factors for heart valve disease and 1. 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ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: developed by the Task Force on Publisher’s Note: All claims expressed in this article are solely those of the authors cardiac pacing and cardiac resynchronization therapy of the European Society of Cardiology (ESC) With the special contribution of the and do not necessarily represent those of their affiliated organizations, or those of European Heart Rhythm Association (EHRA). Eur Heart J. (2021) 42:3427– the publisher, the editors and the reviewers. Any product that may be evaluated in 520. doi: 10.1093/eurheartj/ehab699 this article, or claim that may be made by its manufacturer, is not guaranteed or 15. Eriksson P, Hansson PO, Eriksson H, Dellborg M. Bundle-branch block in endorsed by the publisher. a general male population: the study of men born 1913. Circulation. (1998) 98:2494–500. doi: 10.1161/01.CIR.98.22.2494 Copyright © 2022 Park, Laiz, Díaz del Campo, Martín Martínez, Guerra- 16. Shan R, Ning Y, Ma Y, Liu S, Wu J, Fan X, et al. Prevalence and risk Rodriguez, Alonso-Martin, Sanchez-Vega and Corominas. This is an open-access factors of atrioventricular block among 15 million Chinese health examination article distributed under the terms of the Creative Commons Attribution License (CC participants in 2018: a nation-wide cross-sectional study. BMC Cardiovasc BY). The use, distribution or reproduction in other forums is permitted, provided Disord. (2021) 21:289. doi: 10.1186/s12872-021-02105-3 the original author(s) and the copyright owner(s) are credited and that the original 17. Upshaw Jr CB. Comparison of the prevalence of first-degree atrioventricular publication in this journal is cited, in accordance with accepted academic practice. block in African-American and in Caucasian patients: an electrocardiographic No use, distribution or reproduction is permitted which does not comply with these study III. J Natl Med Assoc. (2004) 96:756–60. terms. 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