Study design and patient enrolment
This retrospective, observational cohort study was conducted at Kokura Memorial Hospital (Kitakyushu, Japan). We reviewed the echocardiographic database for patients with severe AS who visited the hospital from August 2009 to February 2012. We defined severe AS, based on international guidelines, as an aortic valve area (AVA) of ≤1.0 cm2 by transthoracic echocardiography.6 Initially, we identified 595 patients from the database. Of these, 18 patients who underwent TAVR during the follow-up period and 7 patients with lost follow-up data were excluded; the remaining 570 subjects were included in the final analysis (figure 1). The study was reviewed and approved by the Institutional Review Board of Kokura Memorial Hospital, Japan (Approval number: 201402210108).
Figure 1A flowchart of primary findings in the study population as severe aortic stenosis. AVA, aortic valve area; PS, propensity score; SAVR, surgical aortic valve replacement; TAVR, transcatheter aortic valve replacement.
Baseline characteristics and echocardiographic assessment
We collected comprehensive data, including patients’ characteristics, medications and operational information from chart reviews based on the definitions provided. Activity level was defined as active if a patient lived an independent life and as limited if a patient required assisted care. Asymptomatic status was defined as no limitations of ordinary physical activity based on the New York Heart Association functional classification (NYHA class).
All patients underwent two-dimensional echocardiographic examinations, at least, once, during the study period, by professional sonographers using commercially available cardiac ultrasound machines (Vivid 7 Dimension and Vivid E9, GE Healthcare, Horten, Norway; iE33, Philips Medical Systems, Best, The Netherlands). Moreover, all patients who underwent SAVR received a preoperative echocardiographic examination within 1 month of their respective operation date. We considered these records as the baseline characteristics of those undergoing SAVR. Doppler echocardiographic measurements comprised the aortic mean pressure gradient using the simplified Bernoulli equation and an AVA using a standard continuity equation;7 the severity of aortic regurgitation, mitral regurgitation and tricuspid regurgitation was assessed per international guidelines.8
Clinical follow-up and endpoints
The primary endpoint was all-cause mortality. Cardiovascular events, including hospital admission from worsened heart failure (HF), acute coronary syndrome, syncope and non-fatal stroke, were defined as other end points. We gathered information on clinical outcome from patients, families or physicians, either in person or by telephonic interviews. We followed all patients retrospectively until June 2015 to assess their survival status. Perhaps, a time delay before a patient receives surgical treatment can account for marked survival advantages in the SAVR group. Hence, we defined the operation date as day 1 for the follow-up of the SAVR group, whereas the follow-up started on the day of index echocardiography (enrolment) for the non-SAVR group.
Statistical analysis
Although we compared the distributions of continuous variables using Student’s t-test or Wilcoxon rank-sum test, χ² test was used for categorical variables. Continuous data are presented as mean±SD for normally distributed variables or median values with 25th and 75th percentiles for non-normally distributed variables, and categorical data are presented as absolute numbers and percentages. For survival analyses in both the entire population and the matched group, the Kaplan-Meier method was used to estimate the cumulative incidence of all-cause mortality and cardiovascular events in three ways: mortality, mortality and HF requiring admission and mortality and cardiovascular events. Using the log-rank test, we compared the survival and cumulative event-free survival between both groups.
We evaluated patients’ PS, defined as the conditional probability that a patient is assigned to the SAVR group given the patient’s demographics, and measured the disease status and comorbidities.9 We selected 39 baseline covariates: age, sex, body mass index, body surface area, underweight, NYHA class III or IV, estimated glomerular filtration rate (eGFR), hypertension, diabetes mellitus, hyperlipidaemia, coronary artery disease, peripheral vascular disease, previous myocardial infarction, peripheral vascular disease, previous HF admission, prior heart surgery, chronic lung disease, malignancy, chronic liver disease, atrial fibrillation, haemodialysis treatment, peptic ulcer disease, limited activity, current smoker, aortic aneurysm or dissection, angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, calcium channel blocker, antiplatelet therapy, anticoagulant, β-blocker, corticosteroid, AVA, mean aortic pressure gradient, peak aortic velocity ≥4.0 m/s, left ventricular ejection fraction, aortic regurgitation, mitral regurgitation, tricuspid regurgitation and EuroSCORE II. Then, we matched non-SAVR and SAVR patients using PS and a greedy matching technique with a calliper of 0.2 SD of the logit (PS).10 Furthermore, we assessed the balance of the baseline characteristics’ distribution between the two groups by evaluating the standardised mean difference (SMD) as SMD ≤0.1 suggests a balanced distribution of factors between the two groups.11 By performing subgroup analyses, we assessed the correlation between treatment and mortality and cardiovascular events in the groups of patients with prespecified risk factors at baseline of interests—advanced age (≥80 years), asymptomatic status, renal insufficiency (eGFR ≤30 mL/min/1.73 cm2)) and a history of HF.
All statistical analyses were performed using STATA V.14 (STATA, College Station, Texas, USA) and R Statistical Software (V.3.3.2; R Foundation for Statistical Computing, Vienna, Austria). Furthermore, we considered p<0.05 (two-sided) as statistically significant.