Prognostic Impact of Chronic Total Occlusions
Prognostic Impact of Chronic Total Occlusions
The purpose of this study is to determine the prognostic impact of the presence of chronic
 total occlusions (CTO) of the coronary arteries in patients undergoing coronary angiography
 and PCI.
The SCAAR registry

 The SCAAR registry was established in 1999 and is a part of the national SWEDEHEART registry.
 The registry gathers data on all consecutive patients from all hospitals that perform
 coronary angiography and PCI in Sweden. The information about clinical characteristics and
 procedural details is entered into the registry immediately after the procedure by the PCI
 physician after the review of clinical information. SCAAR is independent of commercial
 funding and is sponsored by the Swedish Health Authorities only. The technology has been
 developed and administered by the Uppsala Clinical Research Center, Uppsala, Sweden. Since
 2001, it has a web-based case-report platform with automatic data surveillance.

 Study population

 The study population consisted of all consecutive patients that underwent coronary
 angiography or PCI in Sweden who were registered between 2005 to 2012 in Swedish Coronary
 Angiography and Angioplasty Registry (SCAAR).

 Definitions

 The investigators defined CTO as 100% luminal diameter stenosis and the absence of antegrade
 flow known or assumed to be ≥3 months duration. Coronary artery disease (CAD) was defined as
 a luminal narrowing ≥50% on angiography. Procedural success after PCI treatment of the
 coronary lesion is defined as residual stenosis < 50%, decreased grade of stenosis after
 intervention by at least 20%, TIMI flow ≥ II and no serious complications.

 Study cohort

 The study was based on patients who underwent diagnostic coronary angiography and were
 registered in SCAAR during the period 2005 to January 2012. Only patients who were diagnosed
 with significant coronary artery disease were included in the analyses. A CTO patient was
 identified based on the available information about the percentage of luminal stenosis at the
 level of coronary segments that was introduced in 2005. From this date onwards, the
 information derived from a diagnostic coronary angiogram can also be used to determine if a
 coronary segment was totally occluded. In order to differentiate between acute and chronic
 occlusions, we excluded patients who underwent a procedure for ACS in whom the 100% occlusion
 was located in the same coronary artery as the culprit vessel. Furthermore, we excluded
 patients who underwent a procedure in the same vessel within the previous 3 months. The
 patients with previous coronary artery bypass graft (CABG) surgery were excluded from
 analysis as the patency of the graft could not be determined.

 Validation

 Validation of the CTO definition was performed in a subgroup of 955 patients from one
 university hospital (Sahlgrenska University Hospital) and from three county hospitals (Norra
 Älvsborgs Hospital, Borås Hospital, Skövde Hospital). This subgroup represents 5.7% of all
 identified CTO patients in SCAAR in the study period. The patients were randomly selected by
 means of random number generator. The validation procedure was conducted by a panel
 consisting of five experienced interventional cardiologists. The panelists examined
 individual coronary angiograms according to a monitoring plan defined in advance. Each
 angiogram was evaluated in regard to whether the patient had previous CABG, whether the
 treated occlusion was ≥3 months old and whether 100% segmental stenosis on angiogram was an
 occlusion ≥3 months old. The results from the validation procedure were then compared to the
 data entered in SCAAR.

 Statistical analysis

 Differences in baseline characteristics between the groups were tested with the χ2 test for
 categorical variables while Mann-Whitney U test and Kruskal-Wallis test were used for
 comparison of continuous non-normally distributed variables. Shapiro-Wilks test was used as a
 test for normal distribution. Statistical significance was defined as a P-value <0.05. The
 primary outcome was all-cause mortality. Unadjusted survival was examined using a
 Kaplan-Meier survival curve and the log-rank test. To evaluate the association between
 presence of CTO and mortality, multivariable-adjusted hazard ratios (HR) were calculated
 using Cox proportional-hazards regression models. All tests were two-sided. The potential
 confounders such as; age, gender, diabete, hypertension, hyperlipidemia, smoking status,
 previous PCI, previous MI, extent of CAD, indication, puncture site, any complication,
 primary treatment decision, were all entered into the model. We prespecified six subgroup
 analyses for the following patient categories: indication for angiography and PCI (stable
 angina, UA/non-STEMI, STEMI and other) severity of CAD (one-, two-, three-vessel and left
 main disease) age, gender, diabetes and calendar year. The possible effect modification of
 CTO on risk of dying in the subgroups was analyzed by means of interaction test. Age was
 examined in the interaction with CTO both as a continuous as well as factorial variable
 consisting of four different age groups namely <59, 60-69, 70-79 and >80 years. The
 assumption of proportional hazards for each covariate was reviewed separately by the means of
 log-minus-log survival plots and by formal test based on scaled Schoenfeld residuals.
 Possible multicollinearity between the variables in the model was assessed by calculation of
 variance inflation factor. The database was scrutinized for missing data. A number of
 variables listed above were associated with missing data. In addition to the complete case
 analysis, we applied multiple imputation method to estimate the missing data and performed
 Cox proportional hazards regression with the imputed data set under the assumption that
 missing data are missing at random. The imputation protocol consisted of the chain-equation
 method with a predictive-mean matching algorithm using the same covariates as in the main
 analysis with 20 imputed data sets with addition of cumulative hazard and event indicator.
 Cumulative hazard was estimated with the Nelson-Aalen's test. Due to hierarchical structure
 of SCAAR with clustering of patients within hospitals causing violation of assumption of
 independency between the patients, we applied multilevel modeling with shared frailty Cox
 proportional-hazards regression to adjust for the clustering effect. This was the primary
 model. The secondary model was based on complete-case analysis. All analyses were performed
 using Stata software (version 13.1, StataCorp, College Station, Texas, USA). The imputation
 procedure and subsequent Cox proportional hazards regression estimation was performed
 according to the Rubin's protocol.
Inclusion Criteria:

 -  Patient with angiographic diagnosis of significant CAD registered in SCAAR between
 January 2005 and january 2012

 Exclusion Criteria:

 -  Previous CABG surgery

 -  Missing data on coronary anatomy

 -  Patients who underwent a procedure for ACS in whom the 100% occlusion was located in
 the same coronary artery as the culprit vessel

 -  Patients who underwent a procedure in the same vessel within the previous 3 months