ORIGINAL RESEARCH published: 24 November 2021 doi: 10.3389/fphys.2021.768199 Impact of and Reasons for Not Performing Exercise Training After an Acute Coronary Syndrome in the Setting of an Interdisciplinary Cardiac Rehabilitation Program: Results From a Risk-Op- Acute Coronary Syndrome Ambispective Registry Ignacio Cabrera-Aguilera 1,2,3 , Consolació Ivern 2,4 , Neus Badosa 2,4 , Ester Marco 5,6,7 , Edited by: Luís Salas-Medina 5 , Diana Mojón 4 , Miren Vicente 4 , Marc Llagostera 4 , Nuria Farré 2,4,7* Maria Fernandez-del-Valle, and Sonia Ruiz-Bustillo 2,4,8 Universidad Isabel I, Spain 1 Reviewed by: Facultat de Medicina i Ciències de la Salut, Unitat de Biofísica i Bioenginyeria, Universitat de Barcelona, Barcelona, Spain, 2 Tamara Iturriaga, Heart Diseases Biomedical Research Group, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain, 3 European University of Madrid, Spain Department of Human Movement Sciences, Faculty of Health Sciences, School of Kinesiology, Universidad de Talca, Talca, Garry Tew, Chile, 4 Cardiac Rehabilitation Unit, Department of Cardiology, Hospital del Mar, Barcelona, Spain, 5 Cardiac Rehabilitation Northumbria University, Unit, Physical Medicine and Rehabilitation Department, Parc de Salut Mar (Hospital del Mar – Hospital de l’Esperança), United Kingdom Barcelona, Spain, 6 Rehabilitation Research Group, Hospital del Mar Medical Research Institute, Barcelona, Spain, 7 Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain, 8 Department of Medicine, Universitat *Correspondence: Pompeu Fabra, Barcelona, Spain Nuria Farré NFarreLopez@parcdesalutmar.cat Background and Aims: Exercise training (ET) is a critical component of cardiac Specialty section: rehabilitation (CR), but it remains underused. The aim of this study was to compare This article was submitted to Exercise Physiology, clinical outcomes between patients who completed ET (A-T), those who accepted ET a section of the journal but did not complete it (A-NT), and those who did not accept to undergo it (R-NT), and Frontiers in Physiology to analyze reasons for rejecting or not completing ET. Received: 31 August 2021 Accepted: 31 October 2021 Methods and Results: A unicenter ambispective observational registry study of 497 Published: 24 November 2021 patients with acute coronary syndrome (ACS) was carried out in Barcelona, Spain, Citation: from 2016 to 2019. The primary endpoint was a composite of all-cause mortality, Cabrera-Aguilera I, Ivern C, Badosa N, Marco E, Salas-Medina L, hospitalization for ACS, or need for revascularization during follow-up. Multivariable Mojón D, Vicente M, Llagostera M, analysis was carried out to identify variables independently associated with the primary Farré N and Ruiz-Bustillo S (2021) Impact of and Reasons for Not outcome. Initially, 70% of patients accepted participating in the ET, but only 50.5% Performing Exercise Training After an completed it. The A-T group were younger and had fewer comorbidities. Baseline Acute Coronary Syndrome characteristics in A-NT and R-NT groups were very similar. The main reason for in the Setting of an Interdisciplinary Cardiac Rehabilitation Program: not undergoing or completing ET was rejection (reason unknown) or work/schedule Results From a Risk-Op- Acute incompatibility. The median follow-up period was 31 months. Both the composite Coronary Syndrome Ambispective Registry. Front. Physiol. 12:768199. primary endpoint and mortality were significantly lower in the A-T group compared to the doi: 10.3389/fphys.2021.768199 A-NT and R-NT (primary endpoint: 3.6% vs. 23.2% vs. 20.4%, p < 0.001, respectively; Frontiers in Physiology | www.frontiersin.org 1 November 2021 | Volume 12 | Article 768199 Cabrera-Aguilera et al. Impact of Not Performing Cardiac Rehabilitation mortality: 0.8% vs. 9.1% vs. 8.2%, p < 0.001; respectively). During multivariable analysis, the only variables that remained statistically significant with the composite endpoint were ET completion, previous ACS, and anemia. Conclusion: Completion of ET after ACS was associated with improved prognosis. Only half of the patients completed the ET program, with the leading reasons for not completing it being refusal (reason unknown) and work/schedule incompatibility. These results highlight the need to focus on the needs of patients in order to guarantee that structural barriers to ET no longer exist. Keywords: acute coronary syndrome, cardiac rehabilitation, exercise training, rehabilitation adherence, ischemic heart disease, event-free survival INTRODUCTION This study aimed to assess whether there were epidemiological differences between patients referred for CR according to exercise According to the World Health Organization, ischemic heart compliance and initial attitude toward ET, analyze the reasons disease was the top cause of death in 2000 and 2019, responsible for rejecting or not completing ET, and explore the prognostic for 16% of total deaths each year. Moreover, fatalities due to the impact of each group. disease have seen the most significant increase, rising from over 2 million in 2000 to nearly 9 million in 2019 (Nowbar et al., 2019; World Health Organization [WHO], 2021). Despite the MATERIALS AND METHODS improvements in primary prevention, diagnosis, and treatments (Widimsky et al., 2019), the long-term prognosis of ischemic Study Design and Population heart disease remains poor, with a high rate of acute coronary A total of 497 patients from an ambispective observational syndrome (ACS), need for coronary revascularization, and death registry study carried out at the Hospital del Mar, Barcelona, (Collet et al., 2021). Cardiac rehabilitation (CR) is an integral Spain from November 2016 to September 2019 were included and complex intervention that comprises exercise training (ET), in this analysis. Patients with ST-elevation acute myocardial behavioral change, psychological support, and other strategies to infarction (STEMI), non-ST-elevation acute myocardial control traditional risk factors of cardiovascular disease. Several infarction (non-STEMI), and unstable angina (UA) were studies and meta-analyses have shown that CR is associated with included. The diagnosis was made according to the European better prognosis. Therefore, CR has a class I recommendation Heart Association guidelines (Roffi et al., 2015; Ibanez et al., from the European Society of Cardiology for the management 2018). All patients from our health area were invited to of a cardiac ischemic event (Anderson et al., 2016; Ibanez et al., participate in the CR program (CRP). The only exclusion criteria 2018; Ji et al., 2019; Collet et al., 2021). Unfortunately, CR remains were being from other health areas and the existence of a severe underused due to multiple reasons (Bethell et al., 2008; Balady language barrier. et al., 2011; Serón et al., 2019). On the one hand, many countries and regions do not have CR programs. On the other hand, Cardiac Rehabilitation Program patients are often unwilling or unable to enroll in CR, especially The CRP at the Hospital del Mar is an interdisciplinary program the ET component. Indeed, only 50% of patients referred for CR that combines interventions performed by cardiologists, nurses, end up participating in ET (Dunlay et al., 2014). Although several rehabilitation physicians, physiotherapists, and psychiatrists. studies have analyzed the difference between patients who accept All patients with ACS receive education on healthy habits to undergo ET and those who do not, few studies have studied during the initial ACS hospitalization, or shortly after discharge patients who begin ET but do not complete it. Thus, it is unknown for those hospitalized in other hospitals. Specialized nurses whether patients who begin ET but do not complete it have undertake follow-up visits 3 and 12 months after inclusion in different baseline characteristics and outcomes than patients who the CRP. Patients attend weekly group sessions with healthcare complete ET and those who outrightly reject it. Patient-centered professionals aimed at reinforcing their health education, with care (PCC) has been proposed as a central component for a a particular focus on understanding the pathophysiology of sustainable, affordable, and high-quality healthcare approach. ACS, the role of cardiovascular risk factors, and the importance It underlines the importance of understanding the patient’s of optimal risk factor management, mainly through physical capabilities and resources in order to engage the patient to activity, control of anxiety, smoking cessation, and adherence to participate in care (Ekman et al., 2011). PCC efficiency has been guideline-recommended drugs. demonstrated in several conditions and care levels, including All patients are referred to participate in ET. Patient functional ACS (Fors et al., 2016; Wolf et al., 2019). To provide optimal PCC, status is assessed on enrollment by a treadmill test. Rehabilitation it is critical to know why patients choose not to participate in CR. physicians prescribe the levels and types of exercise for patients This knowledge would improve prognosis. according to their characteristics and risk stratification. The ET Frontiers in Physiology | www.frontiersin.org 2 November 2021 | Volume 12 | Article 768199 Cabrera-Aguilera et al. Impact of Not Performing Cardiac Rehabilitation intervention consists of 25 1-h sessions—five times per week data from a registry collection carried out prospectively between (Monday–Friday from 9 to 10 a.m.) for 5 weeks. Each session July 2018 and September 2019, with all the patients providing starts with a 5-min warm-up period followed by 30 min of written informed consent. Retrospective data collection was cycling (80% of maximal heart rate achieved in an exercise carried out between November 2016 and June 2018, with the test), 20 min of resistance muscle training of upper and lower Ethical Committee approving the inclusion of these group of limbs (weight at 10 RM), and a 5-min cool-down period. An patients to increase the sample size but waiving the need for expert physiotherapist supervises sessions with continuous heart written informed consent by this group, given that the same rate and pulse oximetry monitoring. The workload progression protocol had been carried out before. is adjusted weekly according to the patient’s tolerance (Borg perceived effort scale). Dropout in ET is defined as attending no more than 50% of sessions (Worcester et al., 2004). RESULTS Study Variables Patients’ Baseline Clinical We collected baseline demographic and clinical data and follow- Characteristics up events, viz.: age, gender, BMI, risk factors and comorbidities, The flow chart of the 497 patients included in this study is diagnostics, and basal hospitalization data. Patients were depicted in Figure 1. Although 70% of patients initially accepted classified into three groups: those who completed the ET (A-T), to participate in the ET, 28% of this group did not complete those who outrightly rejected ET (R-NT), and those who accepted the ET for various reasons. Therefore, only 50.5% of the whole but did not complete ET (A-NT). We collected the reasons population completed the ET. for not wanting to perform the ET. When the cause was not Baseline clinical characteristics of the study population are established in the medical record, it was classified as “rejected- summarized in Table 1. In brief, most of the patients were reason unknown.” The primary endpoint was a frequently used men with a diagnosis of STEMI, 1-vessel disease, and preserved composite of all-cause mortality, hospitalization due to ACS, or ejection fraction. No significant differences were found when need for new revascularization during follow-up (Bainey et al., comparing both sexes. Patients who completed ET (A-T) were 2020; Turgeon et al., 2020). younger and had fewer comorbidities. Patients in R-NT and A-NT groups had similar baseline characteristics. Statistics Continuous variables were expressed as mean ± standard deviation (SD) or median and interquartile range (IQR) Reasons for Not Completing the Exercise based on normality distribution assessed by the Kolmogorov– Training Component of the CR Program Smirnov test. Categorical variables were expressed as percentages. The main reason for outrightly rejecting to participate in Differences in baseline characteristics between groups previously or not completing the ET was rejection-reason unknown. defined by level participation in CRP were tested using the χ2 -test Table 2 presents the reasons for non-participation in and non- (categorical variables); and Student’s t-test or the Mann–Whitney completion of the ET component of the CRP. Reasons for U-test, one-way analysis of variance or the Kruskal–Wallis test not completing the ET were qualitatively somewhat different for continuous variables. Univariable and multivariable analyses in women and men. were performed using the Cox proportional hazard regression Only four patients (4% of A-NT) could not complete the model to examine the association between ET participation ET due to cardiovascular complications: one patient with atrial and outcomes. Variables with an overall significance value of fibrillation, one with a high-risk treadmill test, one due to chest p < 0.05 were used for multiple Cox regression analysis to identify pain, and one with ACS. These events did not occur during the strongest predictors of event-free survival. The model was the ET. Work incompatibility and distance/schedule were also adjusted for potential confounders selected by stepwise forward relevant reasons for not performing ET in both the A-NT and inclusion among patient characteristics previously defined. The R-NT groups. It is noteworthy that none of the A-T patients variables included in the multivariable analysis have also been experienced a CV complication while exercising, confirming that associated with the endpoint in several studies (Arnold et al., ET was safe in this group of patients. 2015; Bainey et al., 2020; Turgeon et al., 2020). The log-rank test compared the Kaplan–Meier survival curves. All analysis Prognosis was performed using IBM SPSS Statistics v25 (Armonk, NY, During a median follow-up of 31 (23–39) months, 12% of all United States) and GraphPad Prism 8.0 (San Diego, CA, patients showed a composite outcome of all-cause death, new United States). For all tests, p < 0.05 was considered as ACS, or need for coronary revascularization. The A-T group statically significant. showed an excellent prognosis. In this group, the mortality rate was < 1%. The prognoses in the A-NT and R-NT groups were Ethics similar and worse than that in the A-T group (Table 3). The study was designed in compliance with the ethical principles After adjustment for age, sex, anemia, hypertension, diabetes set forth in the Declaration of Helsinki. The Ethics Committee mellitus, renal disease, previous ACS, peripheral vascular disease, of the Hospital del Mar (Parc de Salut Mar) approved the study type of ACS, and ET compliance, the only variables that (N◦ 2018/7896/I). The data included in this study incorporated remained statistically significant with the composite endpoint on Frontiers in Physiology | www.frontiersin.org 3 November 2021 | Volume 12 | Article 768199 Cabrera-Aguilera et al. Impact of Not Performing Cardiac Rehabilitation FIGURE 1 | Flow chart of patients in the cardiac rehabilitation program. ACS, Acute coronary syndrome; R-NT, Rejected and did not perform training; A-T, Accepted and did exercise training; A-NT Accepted but did not do/complete training; CV, Cardiovascular. Data are expressed in percentages to the preceding category. Data with an asterisk (*) were calculated to refer to the whole cohort. multivariable Cox regression analysis were ET compliance [A- Pardaens et al., 2017). This finding might seem counterintuitive NT, HR 5.6 (95% CI 2.75–13.05); R-NT, HR 4.32 (2.00–9.29)], because higher-risk patients (i.e., those with comorbidities) previous ACS and anemia (Table 4). should be more prone to accept ET to decrease their risk (Bainey Figure 2 shows the Kaplan–Meier survival curves for the et al., 2020). Several reasons might explain why this was not the composite endpoint and all-cause mortality in the three groups; case in this study. On the one hand, patients who completed ET the A-T group shows better survival in both curves. (A-T) might be fitter due to their being younger and having fewer comorbidities, and more open to going to the gym to exercise. Moreover, this group had less history of ACS and presented DISCUSSION more frequently with STEMI. This acute presentation might have prompted them to accept any option that would improve their Although 70% of patients accepted to participate in ET after ACS prognosis. On the other hand, the A-NT and R-NT patients were during a CRP, only 50.5% of the total patients completed the older and had more comorbidities, some of which might have ET protocol. Patients who completed ET (A-T) were younger hindered their ability to exercise (e.g., peripheral vascular disease and had fewer comorbidities. Their prognosis was excellent, with and anemia), and even though the exercise was adapted to the mortality < 1% at a median follow-up of 31 months. Patients needs of the patients, some patients might not have found it who did not complete ET (A-NT and R-NT) had similar baseline valuable and thus rejected it. Surprisingly, there is not much characteristics and prognosis, which was worse than that of information in the literature on patients who initially accept to the A-T group. The main reason for not participating in ET undergo ET but do not start or finish it. Given that they accounted was refusal from the patients and work and schedule/distance for 28% of the patients who initially accepted to undergo ET in incompatibilities, highlighting the need to find ways to engage this study, it is a group that should not be overlooked. Their patients in ET and increase ET logistic capabilities. baseline characteristics were similar to those of the R-NT group Although the initial number of patients who accepted ET was except for a lower prevalence of peripheral vascular disease. 70%, only 50.5% completed the ET protocol, a rate similar to the Reasons for low rates of use of CR are very diverse among 52.5% participation obtained in a population-based surveillance different countries and regions. Barriers to participation in ET study of patients after their first ever myocardial infarction are classified as inherent to the patient’s characteristics or related (Dunlay et al., 2014). Patients who completed the ET were to accessibility of the CRP system (Ruano-Ravina et al., 2016). younger and with fewer comorbidities, observations that are For instance, gender, age, comorbidities, disease perception, consistent with those of other studies (Dunlay et al., 2014; social class, education level or accessibility, and proximity to Frontiers in Physiology | www.frontiersin.org 4 November 2021 | Volume 12 | Article 768199 Cabrera-Aguilera et al. Impact of Not Performing Cardiac Rehabilitation TABLE 1 | Baseline characteristics of patients in the cardiac rehabilitation program and in the three groups. Characteristic/Variable Overall (n = 497) A-T (n = 251) A-NT (n = 99) R-NT (n = 147) p-value* p-value** p-value*** p-value**** Anthropometric Age (years) 62.6 ± 11.9 60.9 ± 10.7 62.5 ± 11.2 65.6 ± 13.6 0.001 0.203 0.056 <0.001 Women 93 (18.7) 45 (17.9) 16 (16.2) 32 (21.8) 0.490 0.695 0.276 0.349 BMI (Kg/m2 ) 27.1 (24.7–30.1) 27.0 (24.7–29.4) 27.3 (23.9–30.9) 27.0 (24.6–30.4) 0.781 0.523 0.901 0.618 Risk factors and comorbidities Hypertension 281 (56.5) 126 (50.2) 58 (58.6) 97 (66.0) 0.008 0.157 0.238 0.002 Hyperlipidemia 324 (65.2) 168 (66.9) 59 (59.6) 97 (66.0) 0.419 0.195 0.308 0.847 Diabetes mellitus 143 (28.8) 55 (21.9) 32 (32.3) 56 (38.1) 0.002 0.042 0.354 0.001 Current smoker 205 (41.3) 95 (37.9) 46 (46.5) 64 (43.5) Previous smoker > 1 year 146 (29.4) 82 (32.7) 25 (25.3) 39 (26.5) 0.705 0.406 0.953 0.585 Previous smoker < 1 year 20 (4.0) 11 (4.4) 3 (3.0) 6 (4.1) COPD 40 (8.1) 15 (6.0) 10 (10.0) 15 (10.2) 0.230 0.177 0.979 0.123 Cerebrovascular disease 23 (4.6) 9 (3.6) 5 (5.1) 9 (6.1) 0.496 0.529 0.722 0.240 Peripheral vascular disease 39 (7.9) 14 (5.6) 3 (3.0) 22 (15.0) <0.001 0.318 0.002 0.002 Anemia 87 (17.5) 29 (11.6) 20 (20.2) 38 (25.9) 0.001 0.036 0.306 <0.001 Renal disease 29 (5.8) 8 (3.2) 5 (5.1) 16 (10.9) 0.006 0.406 0.108 0.002 Arthropathy 10 (2.0) 2 (0.8) 2 (2.0) 6 (4.1) 0.079 0.332 0.371 0.024 Diagnostics and basal hospitalization STEMI 220 (44.3) 120 (47.8) 41 (41.4) 59 (40.1) NSTEMI 174 (35.0) 93 (37.1) 38 (38.4) 43 (29.3) 0.007 0.414 0.139 0.001 Unstable angina 103 (20.7) 38 (15.1) 20 (20.2) 45 (30.6) Hospitalization length (days) 5 (4–7) 5 (3–6) 5 (4–7) 5 (4–7) 0.116 0.169 0.816 0.055 Previous ACS-MI 99 (19.9) 34 (13.6) 21 (21.2) 44 (29.9) <0.001 0.076 0.128 <0.001 One vessel disease 263 (52.9) 144 (57.4) 42 (42.4) 77 (52.4) Two vessel disease 126 (25.4) 59 (23.5) 34 (34.3) 33 (22.5) 0.192 0.138 0.200 0.474 Three vessel disease 87 (17.5) 40 (15.9) 20 (20.2) 27 (18.4) Ejection fraction (%) 58 (52–62) 58 (51–62) 60 (52–63) 59 (54–62) 0.451 0.545 0.695 0.210 Data are mean ± SD, median (IQR), or n (%). p* values for comparing all three groups (null hypothesis: all three groups had the same characteristics). p** values only apply to the comparison of Accepted and did exercise training (A-T) vs. Accepted but did not do/complete training (A-NT) groups. p*** values only apply to the comparison of A-NT vs. Rejected and did not perform training (R-NT) groups. p**** values only apply to the comparison of A-T vs. R-NT groups. BMI, Body mass index; COPD, chronic obstructive pulmonary disease; CV, Cardiovascular; STEMI, ST-elevation myocardial infarction; NSTEMI, non-ST-elevation myocardial infarction; ACS-MI, Acute coronary syndrome-myocardial infarction. TABLE 2 | Description of reasons by sexes for not doing the exercise training in the group that initially refused and those who initially accepted but did not complete exercise training. R-NT Female Male All A-NT Female Male All (n = 147) (n = 32) (n = 115) (n = 99) (n = 16) (n = 83) Rejection-reason unknown 12 (37.5) 45 (39.1) 57 (38.8) Rejection-reason unknown 6 (37.5) 38 (45.8) 44 (44.4) Functional problems 6 (18.8) 16 (13.9) 22 (15.0) Medical recommendation 8 (50.0) 21 (25.3) 29 (29.3) Job/work incompatibility 7 (21.9) 14 (12.2) 21 (14.3) Job/work incompatibility 2 (12.5) 17 (20.5) 19 (19.2) Schedule and distance 1 (3.1) 20 (17.8) 21 (14.3) CV disease 0 (0.0) 4 (4.8) 4 (4.0) Medical recommendation 4 (12.5) 8 (7.0) 12 (8.2) Schedule and distance 0 (0.0) 2 (2.4) 2 (2.0) Language barrier 0 (0.0) 9 (7.8) 9 (6.1) SARS-CoV-2 contingency 0 (0.0) 1 (1.2) 1 (1.0) Social problems 2 (6.3) 3 (2.6) 5 (3.4) Data are n (%). CV, Cardiovascular. the CRP center plays a crucial role in adherence to ET. For Reasons for not accepting to undergo ET, or for accepting but women, barriers to CR participation are multiple and complex, not completing it, were quite similar in the R-NT and A-NT explaining their low participation rates (Forsyth and Deaton, groups. The main reason in both groups (41% of patients) was the 2020; Vidal-Almela et al., 2020). While our study included 18.71% unwillingness of the patients to participate, with no explanations of female, some studies reported an 11–20% lower enrollment, given for this unwillingness. This finding is consistent with those and women were more likely to withdraw from a program than of other studies where 47.5% of patients did not participate in ET men (35% vs. 29%) (Marzolini et al., 2008; Balady et al., 2011). (Worcester et al., 2004; Dunlay et al., 2014). The other reasons Frontiers in Physiology | www.frontiersin.org 5 November 2021 | Volume 12 | Article 768199 Cabrera-Aguilera et al. Impact of Not Performing Cardiac Rehabilitation TABLE 3 | Outcomes of patients included in the cardiac rehabilitation program and in the three groups. Outcome Overall (n = 497) A-T (n = 251) A-NT (n = 99) R-NT (n = 147) p-value* p-value** p-value*** p-value**** Composite Outcome 62 (12.5) 9 (3.6) 23 (23.2) 30 (20.4) < 0.001 < 0.001 0.597 < 0.001 Death 23 (4.6) 2 (0.8) 9 (9.1) 12 (8.2) < 0.001 < 0.001 0.798 < 0.001 New ACS 25 (5.0) 5 (2.0) 7 (7.1) 13 (8.8) 0.006 0.019 0.618 0.002 Revascularization 36 (7.2) 8 (3.2) 12 (12.1) 16 (10.9) 0.002 0.001 0.765 0.002 All-cause hospitalization 168 (33.8) 61 (24.3) 48 (48.5) 59 (40.1) < 0.001 < 0.001 0.195 0.001 All-CV hospitalization 81 (16.3) 22 (8.8) 19 (19.2) 40 (27.2) < 0.001 0.006 0.149 < 0.001 ACS, Acute coronary syndrome; CV, Cardiovascular. Data are n (%). p* values for comparing all three groups (null hypothesis: all three groups had the same characteristics). p** values only apply to the comparison of Accepted and did exercise training (A-T) vs. Accepted but did not do/complete training (A-NT) groups. p*** values only apply to the comparison of A-NT vs. Rejected and did not perform training (R-NT) groups. p**** values only apply to the comparison of A-T vs. R-NT groups. TABLE 4 | Univariable and multivariable Cox regression analyses for the composite endpoint. Univariable HR (95% CI) p-value Adjusted HR (95% CI) p-value A-T 1 (ref) 1 (ref) A-NT 7.12 (3.30–15.40) < 0.001 5.60 (2.75–13.05) < 0.001 R-NT 5.88 (2.79–12.38) < 0.001 4.32 (2.00–9.29) < 0.001 Previous ACS-MI 2.79 (1.68–4.63) < 0.001 1.81 (1.07–3.08) 0.028 Anemia 3.48 (2.09–5.78) < 0.001 2.33 (1.37–3.97) 0.002 Renal disease 2.96 (1.46–6.01) 0.003 Age (years) 1.04 (1.02–1.06) 0.001 Hypertension 1.97 (1.14–3.42) 0.015 Diabetes mellitus 2.02 (1.23–3.34) 0.006 Female 1 (ref) Male 1.22 (0.66–2.25) 0.521 Peripheral vascular 1.33 (0.57–3.10) 0.504 disease STEMI 1 (ref) NSTEMI 1.43 (0.79–2.58) 0.241 Unstable angina 1.88 (1.00–3.53) 0.050 The composite endpoint includes all-cause mortality, hospitalization due to ACS, or the need for new revascularization during follow-up. A-T, Accepted and did exercise training; A-NT, Accepted but did not do/complete training; R-NT, Rejected and did not perform training (R-NT) groups; STEMI, ST-elevation myocardial infarction; NSTEMI, non-ST-elevation myocardial infarction; ACS-MI, Acute coronary syndrome-myocardial infarction. FIGURE 2 | Kaplan–Meier curves for long-term outcome grouped by ET groups (A, composite endpoint cumulative survival; B, cumulative survival). A-T, Accepted and did exercise training; A-NT, Accepted but did not do/complete training; R-NT, Rejected and did not perform training. The composite endpoint includes all-cause mortality, hospitalization due to ACS, or the need for new revascularization during follow-up. Frontiers in Physiology | www.frontiersin.org 6 November 2021 | Volume 12 | Article 768199 Cabrera-Aguilera et al. Impact of Not Performing Cardiac Rehabilitation more frequently mentioned were job/work incompatibility and study completed the ET component in the setting of an schedule and distance, which accounted for 26% of patients interdisciplinary CRP, although 70% of patients accepted that did not participate or withdrew from ET. Reasons for not participating in ET. Patients who completed ET (A-T) were completing ET were different between men and women. They younger and had fewer comorbidities. Their prognosis was also varied according to the time of assessment (initial refusal excellent, with mortality < 1% at a median follow-up of vs. once accepted but not completed), emphasizing the need 31 months. Patients who outrightly rejected participating in to tailor ET to the needs of patients. Only 27% of patients ET and those who began but did not complete it had similar were excluded from ET due to medical reasons, such as the baseline characteristics and prognosis, which was worse than presence of comorbidities. This percentage is significant and that of the A-T group. The main reasons for not participating in highlights the need to focus on what can be changed in the system AT in both groups were refusal-reason unknown and work and to guarantee that structural barriers to ET disappear, so that schedule/distance incompatibility. These results highlight the genuine PCC can be carried, which would greatly increase the need to focus on the needs of the patients in order to minimize number of patients who complete ET and also bridge the gender structural barriers to ET. gap in participation. PCC can help identify intangible barriers, such as those reported by Resurrección et al. (2017), in which traditional ways of CRP with predominantly male presence could DATA AVAILABILITY STATEMENT make women feel uncomfortable. Finally, our results showed an excellent long-term prognosis in patients who completed ET, with The original contributions presented in the study are included a composite of all-cause mortality, hospitalization due to ACS, or in the article/supplementary material, further inquiries can be need for new revascularization in only 3.6%, after more than 2 directed to the corresponding author/s. years of follow-up, and a mortality of 0.8%. In contrast, patients in the R-NT and A-NT groups showed at least four times more risk with the composite endpoint and all-cause mortality, with no significant difference between the two groups. These results ETHICS STATEMENT are consistent with those of other studies that found that the risk The study was designed in compliance with the ethical principles of death or having a recurrent CV event in patients that do not set forth by the Declaration of Helsinki. The Ethics Committee of complete ET is over double the risk in patients who complete it the Hospital del Mar (Parc de Salut Mar) approved the study (N◦ (Pardaens et al., 2017). 2018/7896/I). The patients/participants provided their written informed consent to participate in this study. LIMITATIONS As a single-center study, the results might not apply to other AUTHOR CONTRIBUTIONS settings. Some of the patients were included retrospectively, and that might have potentially led to bias. Still, given that all SR-B and NB contributed to the conception or design of patients followed the same protocol and that the information was the work. NB, CI, MV, ML, DM, and IC-A contributed documented in the medical record in a structured way, we believe to the data acquisition. NF and IC-A performed data that the risk of bias in this study is negligible. The lack of ET analysis and drafted the manuscript. NF, SR-B, and IC-A schedule flexibility in our center might have affected adherence. contributed to data interpretation. EM, SR-B, and LS-M Patients’ participation might have been higher if we had more critically revised the manuscript. All authors approved the liberty to schedule their ET time. Due to the low number of final version of the manuscript and are accountable for all women in our sample size, we cannot comment on the gender aspects of the work. differences in ET participation. CONCLUSION FUNDING Completion of ET after ACS is associated with an improved IC-A was supported by the ANID-PFCHA—Chilean Doctorate prognosis. Only half of the patients in this registry Fellowship 2017; Grant No. 72180089. 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Conflict of Interest: The authors declare that the research was conducted in the 0b013e32830c1ce3 absence of any commercial or financial relationships that could be construed as a Nowbar, A. N., Gitto, M., Howard, J. P., Francis, D. P., and Al-Lamee, R. (2019). potential conflict of interest. Mortality from ischemic heart disease: analysis of data from the world health organization and coronary artery disease risk factors from NCD risk factor Publisher’s Note: All claims expressed in this article are solely those of the authors collaboration. Circ. Cardiovasc. Qual. Outcomes 12:e005375. and do not necessarily represent those of their affiliated organizations, or those of Pardaens, S., Willems, A. M., Clays, E., Baert, A., Vanderheyden, M., Verstreken, the publisher, the editors and the reviewers. Any product that may be evaluated in S., et al. (2017). The impact of drop-out in cardiac rehabilitation on outcome this article, or claim that may be made by its manufacturer, is not guaranteed or among coronary artery disease patients. Eur. J. Prev. Cardiol. 24, 1490–1497. endorsed by the publisher. doi: 10.1177/2047487317724574 Resurrección, D. M., Motrico, E., Rigabert, A., Rubio-Valera, M., Conejo-Cerón, Copyright © 2021 Cabrera-Aguilera, Ivern, Badosa, Marco, Salas-Medina, Mojón, S., Pastor, L., et al. (2017). Barriers for nonparticipation and dropout of women Vicente, Llagostera, Farré and Ruiz-Bustillo. This is an open-access article distributed in cardiac rehabilitation programs: a systematic review. J. Womens Health 26, under the terms of the Creative Commons Attribution License (CC BY). The use, 849–859. doi: 10.1089/jwh.2016.6249 distribution or reproduction in other forums is permitted, provided the original Roffi, M., Patrono, C., Collet, J.-P., Mueller, C., Valgimigli, M., Andreotti, F., et al. author(s) and the copyright owner(s) are credited and that the original publication (2015). 2015 ESC guidelines for the management of acute coronary syndromes in this journal is cited, in accordance with accepted academic practice. No use, in patients presenting without persistent ST-segment elevationTask force for distribution or reproduction is permitted which does not comply with these terms. Frontiers in Physiology | www.frontiersin.org 8 November 2021 | Volume 12 | Article 768199