Percutaneous coronary intervention and 30‐day unplanned readmission with chest pain in the United States (Nationwide Readmissions Database)

Abstract Percutaneous coronary intervention (PCI) improves anginal chest pain in most, but not all, treated patients. PCI is associated with unplanned readmission for angina and non‐specific chest pain within 30‐days of index PCI. Patients with an index hospitalization for PCI between January–November in each of the years 2010–2014 were included from the United States Nationwide Readmissions Database. Of 2 723 455 included patients, the 30‐day unplanned readmission rate was 7.2% (n = 196 581, 42.3% female). This included 9.8% (n = 19 183) with angina and 11.1% (n = 21 714) with non‐specific chest pain. The unplanned readmission group were younger (62.2 vs 65.1 years; P < 0.001), more likely to be females (41.0% vs 34.2%; P < 0.001), from the lowest quartile of household income (32.9% vs 31.2%; P < 0.001), have higher prevalence of cardiovascular risk factors or have index PCI performed for non‐acute coronary syndromes (ACS) (OR:3.46, 95%CI 3.39–3.54). Factors associated with angina readmissions included female sex (OR:1.28, 95%CI 1.25–1.32), history of ischemic heart disease (IHD) (OR:3.28, 95%CI 2.95–3.66), coronary artery bypass grafts (OR:1.79, 95%CI 1.72–2.86), anaemia (OR:1.16, 95%CI 1.11–1.21), hypertension (OR:1.13, 95%CI 1.09, 1.17), and dyslipidemia (OR:1.10, 95%CI 1.06–1.14). Non‐specific chest pain compared with angina readmissions were younger (mean difference 1.25 years, 95% CI 0.99, 1.50), more likely to be females (RR:1.13, 95%CI 1.10, 1.15) and have undergone PCI for non‐ACS (RR:2.17, 95%CI 2.13, 2.21). Indications for PCI other than ACS have a greater likelihood of readmission with angina or non‐specific chest pain at 30‐days. Readmissions are more common in patients with modifiable risk factors, previous history of IHD and anaemia.


| INTRODUCTION
Percutaneous coronary intervention (PCI) is indicated for acute coronary syndromes (ACS) or the relief of anginal symptoms secondary to myocardial ischemia, in patients with obstructive coronary artery disease (CAD). Around 3 million procedures are performed worldwide every year. The results of recent randomized, controlled trials of clinical strategies involving invasive management of CAD have not provided evidence of clear benefits for coronary revascularization over medical therapy in patients with chronic coronary syndromes (CCS). 1,2 In the ABSORB-4 trial, which compared clinical outcomes in patients treated with either a bioresorbable scaffold or a 3rd generation drug eluting stent, the occurrence and time-course of angina post-PCI was similar in both groups, occurring in 11% of subjects by 30 days and 22% of patients by 1-year. 3 The clinical characteristics associated with anginal chest pain at these time-points and experience in less-selected, real-world populations are uncertain.
Readmission within 30 days following PCI is not uncommon, with a broad spectrum of etiologies and degrees of severity. 4 Readmissions are commonly secondary to cardiac-related disorders or PCI complications and it is reported that readmission is associated with a greater risk of mortality. [5][6][7][8] In this study, we accessed a large, national readmissions database to investigate the proportion of patients re-admitted to hospital with chest pain attributed to angina or non-specific chest pain within 30 days after PCI for ACS or CCS and the associated clinical characteristics. In addition, we evaluated the cost burden of chest pain readmissions compared with readmissions due to other causes.  Table A1).
Demographic, comorbidity at index admission and outcome data as well as detail of inpatient stay was captured through a combination of NRD coding, ICD-9 and Elixhauser comorbidity codes. Cost-to-charge ratios were applied to total charges as recommended by HCUP in order to provide an estimate of inpatient cost.
The primary outcome of this analysis is 30-day readmission with a primary diagnosis of chest pain post-PCI, and variables associated with readmission. A sub-group analysis of the characteristics of patients with a primary diagnosis of angina and non-specific chest pain is also performed.
Statistical analysis was performed using IBM Statistics SPSS (version 24.0). Weighting is performed using sample discharge weights.
Dichotomization of patients based on the presence or absence of readmission within 30 days and subsequent descriptive statistics are presented. Chi-square or Independent Student-T testing with 95% two-tailed significance was utilized for comparing patient demographics. Multiple logistic regression analyses were performed to evaluate the association between these variables and readmission within 30-days with angina, non-specific chest pain and the combined population readmitted with angina or non-specific chest pain. Furthermore, the relative risk (RR) of association with variables and readmission within 30-days of angina versus non-specific chest pain is also evaluated.  reasons for exclusion are described in Figure 1. Of note, 326 759

| RESULTS
were excluded due to a December discharge date. In total, 104 696 patients were excluded from analysis due to missing demographic, discharge or mortality data.  were less likely to be observed compared with those who were not readmitted within 30-days ( Figure 3).  Figure 2).    Chest pain after PCI may be experienced in 36% to 42% of patients undergoing both elective and emergent PCI. [15][16][17] It is most commonly described in the first 24 h following PCI but is described as occurring within the first 3 weeks. 16 In addition to non-cardiac causes it is important to distinguish patients with benign chest pain from critical chest pain after PCI due to acute stent thrombosis, incomplete revascularization, or disease progression affecting alternative coronary regions. However, risk stratification in these patients is challenging and may be influenced by the presence of persistently elevated cardiac enzymes or electrocardiograph evolution in the absence of new myocardial injury. [18][19][20] Benign chest pain and patients with stable angina post-PCI pain in the absence of ACS, pulmonary or upper gastrointestinal pathologies is therefore understandably recorded in up to one third of overall PCI re-admissions. 21,22 No standard nomenclature for the clinical phenomenon of chest pain post-PCI currently exists due to differing opinions of etiology and there are no guidelines for a standardized approach to management. 23 A further entity may include the psychological burden associated with a diagnosis of non-specific chest pain and it is estimated that anxiety disorders are prevalent in 30-50% of these patients. 24 Somatization disorders with chest pain symptoms may influence readmission, particularly in non-ACS PCI indications.

| Healthcare implications of hospital readmission post-PCI
Readmissions are a significant source of burden both on the patient and the healthcare system, which is often used as a proxy-marker for quality of care and penalty systems are implemented for providers with greater proportions of readmission. 25 Patients with chest pain constitute between 0.6 to 2.4% of unplanned presentations to emergency departments and up to one in four admissions to medical and cardiology wards. [26][27][28][29] In the United Kingdom, this represents a significant burden with non-ACS chest pain equating to an average of 15.8 and 16.8 bed days per 1000 population for angina and non-specific chest pain respectively with standalone 30-day mortalities of 1.5% and 0.7%. 28 The incidence and demographical distribution of patients readmitted with chest pain syndromes has not previously been explored. Therefore, the burden on health services as well as mortality and major adverse cardiac event (MACE) rate for patients readmitted with chest pain post-PCI is not clearly defined.
Our study involved a large sample that is likely to be reasonably representative of the US population undergoing PCI. The NRD has been utilized previously in patients with chest pain, which provides precedent for selection in this study. 30 Local audit and assessment of chest pain readmissions should be encouraged in order to establish local requirement for interventions, which may reduce readmissions with non-specific chest pain and angina following PCI. This would ensure appropriate utilization of available resources and financial investment dependent on the localized burden of readmissions.

| Associations with cardiovascular risk factors: implications for risk stratification
Demographic factors associated with higher likelihood of unplanned readmission in this sample are in keeping with known cardiovascular risk factors. However, smoking in this sample was not associated with increased readmission at 30 days. This is based on index smoking status and it is plausible that this may be subject to the smoking modification and cessation programmes, which are commonplace in the management of patients with coronary disease. Patients with heart failure, valvular heart disease and non-cardiac vascular disease were observed to be less likely to be re-admitted at 30-days. This is in part due to the proportion undergoing PCI for ACS in whom ventricular dysfunction if present will be identified following PCI rather than as a co-morbidity on index admission and may also be secondary to increased involvement of secondary care outpatient services in their management and treatment planning.
Optimization of modifiable risk factors prior to intervention is performed in surgical patients and the pre-operative assessment is commonplace in order to improve surgical morbidity and mortality. 31 33 Male gender was observed in the majority of all groups in keeping with gender as a known risk factor of cardiovascular disease. Anaemia in this dataset is associated with increased readmission with a primary diagnosis of angina at 30-days following PCI. Although discharge haemoglobin concentrations are not provided in the database, this may provide an area of potential modification for patients prior to being discharged following PCI.
One evidence-based example of an intervention to reduce readmissions following PCI is a multimodal strategy as described by Tanguturi et al (2016). 34 This involved a risk assessment of readmission with the production of patient videos regarding subsequent chest pain or symptoms of heart failure. In addition, a formal clinic review with a cardiology fellow and a computerized alert system for re-presentations facilitated early cardiologist review. This package of interventions reduced 30-day hospital readmission from 9.6% to 5.3% over the 4-year study period.

| CONCLUSIONS
Our study provides insights into the prevalence, risk factors and health burden of readmission with angina or non-specific chest pain following PCI. Secondary prevention measures to reduce cardiovascular risk such as correction of anaemia may help to optimize the clinical status of patients prior to undergoing PCI. PCI performed for an indication other than ACS is associated with a greater likelihood of readmission with angina or non-specific chest pain at 30-days within this cohort and further investigation of the etiology within these patients is required.

ACKNOWLEDGMENTS
The authors would like to thank the Healthcare Cost and Utilization Project for access to the Nationwide Readmissions Database.