Study design
The China Heart Failure Surgery Registry (China-HFSR) was led by Fuwai Hospital and other representative cardiac centres in different regions around China. In total, 94 centres covering a broad geographic region were included as participants in the study. We included patients ≥ 17 years old who underwent CABG from January 2012 to June 2017 with documented left ventricular ejection fraction (LVEF) < 50%. Patients were excluded if they underwent concomitant valve or other surgeries. These patients were then stratified according to preoperative smoking status (Fig. 1). Current smokers were defined as those who smoked within 1 month before admission. Ex-smokers were defined as those who quitted smoking for at least 1 month. Non-smokers were defined as those who never smoked. All CABG procedures represented standard surgical approaches to surgical myocardial revascularization with and without the use of cardiopulmonary bypass support. This study was approved by the institutional review board at Fuwai Hospital (approval number 887, April 25th, 2017) and carried out in accordance with relevant guidelines and regulations. The informed consent was signed by participants.
Data collection
All data were collected at the local sites from the medical records. The requirements for data collection and the definitions of variables were clearly identified. All data were entered into the database separately by two trained technicians using standardized electronic case report forms at the local sites and then submitted online to the data processing centre. Two separate reviewers from the data processing centre randomly selected and assessed 5–10% of each of the participating centres’ medical records during annual on-site audits. We compared the data in the database and the original medical records. A committee composed of physicians and surgeons determined the correct final value when there was a disagreement. In all patients included in China-HFSR database, 91 (1.4%) of them s don’t have height data, and 78 (1.2%) of which were without weight. Considering the fact that they only accounted for a very small proportion of our patients, we imputed missing continuous variables (height and weight) with different mean values for different sex gender.
Clinical data
The preoperative variables including age, gender, body mass index, New York Heart Association (NYNH) classification, Canadian Cardiovascular Society (CCS) classification, diabetes mellitus (DM), hypertension, hyperlipidaemia, renal failure, chronic obstructive pulmonary disease (COPD), cerebrovascular accident, carotid disease and other peripheral arterial disease, preoperative atrial fibrillation, previous myocardial infarction (MI), percutaneous transluminal coronary angioplasty (PTCA) history, Number of diseased vessels, left main CAD, LVEF, preoperative creatinine and prior cardiovascular surgeries. Data regarding preoperative intra-aortic balloon pump (IABP) insertion, operative priority and cardiopulmonary bypass using were also collected.
The major postoperative complications included re-intubation, prolonged ventilation (> 24 h), MI, mediastinal infection, stroke, renal failure, multiple organ dysfunction syndrome and reoperation for bleeding. MI was counted as a complication if it newly occurred postoperatively meet the following criteria (≥ 1): (1) MI documented in the medical record with an elevation of cardiac troponin values with at least one value above the 10 times 99th percentile upper reference limit; (2) electrocardiograph-documented ST-segment elevation in evolution, Q waves 0.03 seconds in width and/or one-third or greater of the total QRS complex in 2 or more contiguous leads; (3) new left bundle branch block.[12] Mediastinal infection was defined according to the published expert consensus.[13] Stroke was defined as a central neurological deficit persisting > 24 hours (i.e., extremity weakness or loss of motion, loss of consciousness, loss of speech, visual field cuts). Renal failure was defined as an increase in serum creatinine level to > 4 mg/dL, 3 times the most recent preoperative creatinine level, or a new postoperative need for dialysis. Reoperation for bleeding was defined as chest tube drainage ≥ 200 mL/h for at least 3 hours requiring surgical intervention.
Statistical analysis
Continuous variables are expressed as either mean ± standard deviation (SD) or medians and interquartile range (IQR) depending upon variable distribution. Categorical variables are presented as frequencies and percentages. We performed a t-test for normally distributed continuous variables; otherwise, the Mann-Whitney U test or Kruskal-Wallis H test was used. This was followed by the Bonferroni t-test with a corrected P value of 0.05/3. Chi square tests or Fisher’s exact tests were used for categorical variables.
We used the following 2 techniques to adjust for potential confounders when comparing outcomes of the different smoking status groups: multiple logistic regression modelling and propensity matching. For the regression-based analyses, the association between preoperative beta-blocker use and each clinical end point were adjusted for baseline patient risk by inclusion of the following validated and widely accepted measures of patient-level covariates: age, body mass index, sex, diabetes mellitus, hypertension, hyperlipidemia, chronic renal failure, chronic obstructive pulmonary disease, cerebrovascular accident, carotid disease, peripheral artery disease, previous MI, PTCA history, LVEF, preoperative creatinine, CCS classification, NYHA classification, triple vessel disease, Left main CAD, preoperative IABP, operative priority, off-pump technique and prior cardiovascular history. Model results are reported as odds ratios (OR) with a 95% confidence interval (CIs).
The second method of adjusting for potential confounders involved matching patients with similar estimated probability of smoking status (propensity score). The propensity score was calculated by a multivariable logistic regression model which was developed using the same covariates listed above for the regression-based analyses. Then we matched patients in a 1:1 fashion without replacement.[14] We performed PS matching between ex-smokers and non-smokers, and between current and non-smokers. ORs with 95% CIs comparing the frequency of each end point for ex-smokers vs non-smokers and current smokers vs non-smokers were estimated using univariable logistic regression.
Additional analysis were performed to examine whether the association between smoking status and mortality differed across prespecified subgroups based on age, sex, ejection fraction, diabetes mellitus, hypertension and chronic lung disease. Subgroup-specific ORs were estimated and displayed with 95% CIs.
All reported P values are 2 sided, and values of P < 0.05 were considered to indicate statistical significance .When applying for multiple comparison, a Bonferroni adjustment with a corrected P value of 0.0167 (0.05/3) was introduced. All statistical analysis was performed using SPSS version 22.0 (IBM Corp., Armonk, NY).