Merril L. Knudtson

Current Perspectives on Coronary Chronic Total Occlusions The Canadian Multicenter Chronic Total Occlusions Registry

OBJECTIVES The purpose of this study was to determine the prevalence, clinical characteristics, and management of coronary chronic total occlusions (CTOs) in current practice. BACKGROUND There is little evidence in contemporary literature concerning the prevalence, clinical characteristics, and treatment decisions regarding patients who have coronary CTOs identified during coronary angiography. METHODS Consecutive patients undergoing nonurgent coronary angiography with CTO were prospectively identified at 3 Canadian sites from April 2008 to July 2009. Patients with previous coronary artery bypass graft surgery or presenting with acute ST-segment elevation myocardial infarction were excluded. Detailed baseline clinical, angiographic, electrocardiographic, and revascularization data were collected. RESULTS Chronic total occlusions were identified in 1,697 (18.4%) patients with significant coronary artery disease (>50% stenosis in ≥1 coronary artery) who were undergoing nonemergent angiography. Previous history of myocardial infarction was documented in 40% of study patients, with electrocardiographic evidence of Q waves corresponding to the CTO artery territory in only 26% of cases. Left ventricular function was normal in >50% of patients with CTO. Half the CTOs were located in the right coronary artery. Almost half the patients with CTO were treated medically, and 25% underwent coronary artery bypass graft surgery (CTO bypassed in 88%). Percutaneous coronary intervention was done in 30% of patients, although CTO lesions were attempted in only 10% (with 70% success rate). CONCLUSIONS Chronic total occlusions are common in contemporary catheterization laboratory practice. Prospective studies are needed to ascertain the benefits of treatment strategies of these complex patients.

Survival After Coronary Revascularization Among Patients With Kidney Disease

Background—The optimal approach to revascularization in patients with kidney disease has not been determined. We studied survival by treatment group (CABG, percutaneous coronary intervention [PCI], or no revascularization) for patients with 3 categories of kidney function: dialysis-dependent kidney disease, non–dialysis-dependent kidney disease, and a reference group (serum creatinine <2.3 mg/dL). Methods and Results—Data were derived from the Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH), which captures information on all patients undergoing cardiac catheterization in Alberta, Canada. Characteristics and patient survival in 662 dialysis patients (1.6%) and 750 non–dialysis-dependent kidney disease patients (1.8%) were compared with the remainder of the 40 374 patients (96.6%). For the reference group, the adjusted 8-year survival rates for CABG, PCI, and no revascularization (NR) were 85.5%, 80.4%, and 72.3%, respectively (P<0.001 for CABG versus NR; P<0.001 for PCI versus NR). Adjusted survival rates were 45.9% for CABG, 32.7% for PCI, and 29.7% for NR in the nondialysis kidney disease group (P<0.001 for CABG versus NR; P=0.48 for PCI versus NR) and 44.8% for CABG, 41.2% for PCI, and 30.4% for NR in the dialysis group (P=0.003 for CABG versus NR; P=0.03 for PCI versus NR). Conclusions—Compared with no revascularization, CABG was associated with better survival in all categories of kidney function. PCI was also associated with a lower risk of death than no revascularization in reference patients and dialysis-dependent kidney disease patients but not in patients with non–dialysis-dependent kidney disease. The presence of kidney disease or dependence on dialysis should not be a deterrent to revascularization, particularly with CABG.

Associations Between Acute Kidney Injury and Cardiovascular and Renal Outcomes After Coronary Angiography

Background— Acute kidney injury (AKI) is associated with early mortality after percutaneous coronary revascularization procedures, but its prognostic relevance to long-term clinical outcomes remains controversial. Methods and Results— We conducted a retrospective study of 14 782 adults who received coronary angiography in the province of Alberta, Canada, between 2004 and 2006. AKI was identified on the basis of changes in serum creatinine concentration within 7 days of the procedure according to AKI Network criteria. The associations between AKI and long-term outcomes, including mortality, end-stage renal disease, and cardiovascular and renal hospitalizations, were studied with the use of Cox regression of multiple failure times. The adjusted risk of death increased with increasing severity of AKI; compared with no AKI, the adjusted hazard ratio for death was 2.00 (95% confidence interval, 1.69 to 2.36) with stage 1 AKI and 3.72 (95% confidence interval, 2.92 to 4.76) with stage 2 or 3 AKI. The adjusted risk of end-stage renal disease requiring renal replacement therapy also increased according to the severity of AKI (hazard ratio, 4.15 [95% confidence interval, 2.32 to 7.42] and 11.74 [95% confidence interval, 6.38 to 21.59], respectively), as did the risks of subsequent hospitalizations for heart failure and acute renal failure. Conclusions— These findings inform the controversy surrounding AKI after angiography, demonstrating that it is a significant risk factor for long-term mortality, end-stage renal disease, and hospitalization for cardiovascular and renal events after coronary angiography.

Sequential thallium-201 myocardial perfusion studies after successful percutaneous transluminal coronary artery angioplasty: delayed resolution of exercise-induced scintigraphic abnormalities.

To characterize the sequential changes of myocardial perfusion scintigraphy in patients with coronary artery disease (CAD) after complete revascularization, 43 patients underwent exercise thallium-201 (201Tl) myocardial perfusion scintigraphy before and at 9 +/- 5 days, 3.3 +/- 0.6, and 6.8 +/- 1.2 months after percutaneous transluminal coronary angioplasty (PTCA). Only patients with single-vessel CAD, without previous myocardial infarction, and without evidence of restenosis at 6 to 9 months after PTCA were included. Perfusion scans were analyzed blindly with the use of a new quantitative method to define regional myocardial perfusion in the topographic distribution of each coronary artery, which was shown to be reproducible (r = .94 or higher and SEE of 7% or less, between repeated measures by one and two operators). At 4 to 18 days after PTCA, the mean treadmill walking time increased by 123 +/- 42 sec, mean exercise-induced ST segment depression decreased by 0.6 +/- 0.3 mm, group maximal heart rate increased by 20 +/- 9 beats/min, and group systolic blood pressure at peak exercise increased by 24 +/- 10 mm Hg, compared with pre-PTCA values (p less than .001). However, no group differences were noted in these variables between the three post-PTCA stages. Myocardial perfusion in the distribution of the affected (dilated) coronary artery, on the other hand, improved progressively. In the 45 degree left anterior oblique view for instance, myocardial perfusion increased at 9 days after PTCA (from 68 +/- 24% before PTCA to 91 +/- 9%, p less than .001) and at 3.3 months after PTCA (101 +/- 8%, p less than .05 vs 9 days after PTCA), but no further significant changes were seen at 6.8 months after PTCA (102 +/- 8%). Similar changes were noted in the other two views. No relationship between minor complications during PTCA and delayed improvement on the 201Tl was observed. Myocardial ischemia was diagnosed in 12 of the 43 scans recorded a few days after PTCA, but in none recorded at later stages. We conclude that 201Tl scans after PTCA often show delayed improvement and therefore, an abnormal myocardial perfusion scan soon after PTCA does not necessarily reflect residual coronary stenosis or recurrence.

Sex Differences in Access to Coronary Revascularization after Cardiac Catheterization: Importance of Detailed Clinical Data

Context Women are less likely to be offered therapeutic cardiac procedures than men; however, the reasongender bias or clinical factorsis unknown. Contribution This study of coronary revascularization procedures during the year after catheterization compared men and women with the same extent of coronary artery disease and ejection fraction. The rate of coronary revascularization was the same in men and women. Implications The sex differences in cardiac procedure rates after catheterization appear to reflect appropriate decisions rather than gender bias. However, sex-based differences in catheterization rates remain unexplained. The Editors Reports of sex differences in the likelihood of undergoing cardiac procedures have led to suggestions of gender bias in cardiac care decision making (1-14). Other proposed explanations for the variation in use of cardiac procedures between sexes include differing patient preferences or differing clinical characteristics (for example, smaller coronary vessels in women). Earlier studies did not unanimously find sex differences in cardiac procedure rates; some studies reported equivalent procedure rates for men and women (15-21). The inconsistency across studies may be related to differences in geographic regions and health systems. However, another possible explanation is that many earlier studies evaluated highly selected patient samples that may not reflect processes of care at a population level. Yet another possible explanation is that the published studies on this issue have used various data sources, ranging from highly detailed data from clinical trials to sparsely detailed administrative data. The Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) is a population-based registry that captures detailed clinical information on all adult patients undergoing cardiac catheterization in the province of Alberta, Canada (22). The clinically detailed data generated by APPROACH provide a unique opportunity to study sex differences in access to revascularization after cardiac catheterization without the limitations of a nonrepresentative study sample or insufficiently detailed clinical data. Furthermore, the detailed APPROACH data allow us to assess whether comorbid conditions, extent of coronary disease, and ejection fraction account for or explain any observed sex differences in access to revascularization procedurespercutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) surgery. Using a two-step process, we statistically adjusted crude (unadjusted) rates of cardiac revascularization for men and women in the year following cardiac catheterization. The first (partial) adjustment was based on baseline clinical variables that are routinely available in most databases, including administrative databases. The second (full) adjustment also controlled for extent of coro nary disease and ejection fraction, variables that are uniquely available for a large unselected patient population in APPROACH data. Methods Data Source and Variables The APPROACH database is an inception cohort database that captures clinical information on all patients undergoing cardiac catheterization in Alberta, Canada (22). This province has a population of approximately 2.8 million persons, of whom 10% identify themselves as ethnic minorities (3.5% are of Chinese ethnicity, 2% are of South Asian ethnicity, 1% are black, and 4.5% are aboriginal inhabitants). In 1996, median individual income levels for postal codedefined regions ranged from

Acute kidney injury following coronary angiography is associated with a long-term decline in kidney function

12 000 to

Contrast-Induced Acute Kidney Injury and Risk of Adverse Clinical Outcomes After Coronary Angiography A Systematic Review and Meta-Analysis

37 000 Canadian per year. Sixty-seven percent of Albertans older than 20 years of age have a high school diploma, and 25% have some university-level education. Patients in APPROACH are followed longitudinally for assessment of long-term outcomes after cardiac catheterization. Clinical risk variables recorded at the time of cardiac catheterization are age, sex, diabetes mellitus, cerebrovascular disease, congestive heart failure, chronic pulmonary disease, elevated creatinine level ( 200 mmol/L [ 22.62 g/L]), dialysis status, hyperlipidemia, hypertension, liver or gastrointestinal disease, malignancy or metastatic disease, previous myocardial infarction, previous thrombolytic therapy for myocardial infarction, and peripheral vascular disease. The indication for catheterization is recorded in one of four categories: myocardial infarction within 8 weeks of catheterization, unstable angina, stable angina, or other (for example, arrhythmias without associated angina, or study protocols). The results of cardiac catheterization, including extent of coronary disease and left ventricular ejection fraction, are also recorded. We graded extent of coronary disease according to six categories: normal or near normal, one- to two-vessel disease, two-vessel disease with proximal left anterior descending artery involvement, three-vessel disease, three-vessel disease with proximal left anterior descending artery involvement, or left main disease. A diseased vessel was one that contained a lesion involving more than 50% of the vessel diameter. Left ventricular ejection fraction was graded according to five categories: greater than 50%, 30% to 50%, less than 30%, ventriculography not done (usually because of renal insufficiency or severely depressed cardiac function), and data missing. The APPROACH database accurately captures the occurrence of revascularization procedures in Alberta hospitals and the time to revascularization after cardiac catheterization. We analyzed data from patients undergoing cardiac catheterization from 1995 through 1998, with follow-up data through 1999. The Ethics Review Boards of the University of Calgary and the University of Alberta, Canada, approved the APPROACH study protocol. Statistical Analysis We performed a chi-square test and two-sample t-tests to compare the clinical characteristics of men and women undergoing catheterization. Chi-square tests and log-rank tests were used to compare the unadjusted proportions of men and women having revascularization procedures within 1 year after cardiac catheterization. We then used multivariable Cox proportional-hazards analyses to control revascularization rates for differences in clinical characteristics between men and women undergoing catheterization. For these analyses, we modeled time to 1) any revascularization procedure, 2) PCI, and 3) CABG surgery, with follow-up to 1 year. We initially calculated crude relative risks for procedures for women relative to men and then sequentially modeled two sets of variables. First, for the partially adjusted model, we used a set of clinical variables (age, indication for cardiac catheterization, cardiac history, and the comorbidity variables listed earlier) that would generally be available in most administrative databases (throughout the paper, we call this initial step partial adjustment). Second, for the fully adjusted model, we added two clinical variables, left ventricular ejection fraction and extent of coronary disease, that are uniquely available at a population level in the clinically detailed APPROACH database. The relative risk for women compared with men was the variable of interest for each of the models generated. We calculated and plotted risk-adjusted time-to-revascularization curves for men and women by applying the corrected group prognosis method to the proportional hazards models that generated fully adjusted relative risks (23). By plotting log[log S(t)] versus t and log(t) for all of the above models, we found that the proportional hazards assumption was appropriate for all variables included in the models, except the variable of indication for cardiac catheterization. Therefore, we handled cardiac catheterization as a stratification variable in our models. To assess model performance, we also plotted both martingale and deviance residuals for individual observations and found that none of the observations were widely deviant (that is, almost all deviance residuals were between 1.96 and 1.96). We examined influential observations by measuring the changes in the coefficients after dropping each observation from the data. For sex, the most influential observations changed the coefficient by less than 5% of the standard error. The software product used to perform data analyses was S-PLUS 5 for Linux, version 5.1 (Insightful Corp., Seattle, Washington). Role of the Funding Sources The funding sources had no role in the design, conduct, or reporting of this study. Results A total of 21 816 patients underwent cardiac catheterization in Alberta between 1 January 1995 and 31 December 1998. Of these patients, 15 409 (70.6%) were men and 6407 (29.4%) were women. Within 1 year after catheterization, 8488 of the 15 409 men (55.1%) had undergone a revascularization procedure (PCI or CABG surgery) compared with only 2574 of the 6407 women (40.2%) (P < 0.001). The proportion having undergone PCI at 1 year was 32.2% for men versus 26.1% for women (P < 0.001). The proportion having CABG surgery by 1 year after catheterization was 22.9% for men and only 14.0% for women (P < 0.001). In a proportional hazards analysis, the corresponding crude relative risk (that is, the likelihood) for having any revascularization procedure for women compared with men was 0.67 (95% CI, 0.65 to 0.71). For PCI and CABG surgery, the corresponding relative risks were 0.77 (CI, 0.73 to 0.82) and 0.54 (0.51 to 0.58), respectively. Thus, in relative terms, women were 33% less likely to undergo any revascularization procedure, 23% less likely to undergo PCI, and 46% less likely to undergo CABG surgery than were men. Clinical Characteristics Clinical characteristics of men and women differed (Table 1). Men tended to be younger and had fewer comorbid conditions, including a lower prevalence of chronic lung disease, cerebrovascular disease, hypertension, diabetes mellitus, liver disease, and congestive heart failure. However, men

Multiple imputation versus data enhancement for dealing with missing data in observational health care outcome analyses

To determine whether acute kidney injury results in later long-term decline in kidney function we measured changes in kidney function over a 3-year period in adults undergoing coronary angiography who had serum creatinine measurements as part of their clinical care. Acute kidney injury was categorized by the magnitude of increase in serum creatinine (mild (50-99% or >or=0.3 mg/dl) and moderate or severe (>or=100%)) within 7 days of coronary angiography. Compared to patients without acute kidney injury, the adjusted odds of a sustained decline in kidney function at 3 months following angiography increased more than 4-fold for patients with mild to more than 17-fold for those with moderate or severe acute kidney injury. Among those with an estimated glomerular filtration rate after angiography less than 90 ml/min per 1.73 m(2), the subsequent adjusted mean rate of decline in estimated glomerular filtration rate during long-term follow-up (all normalized to 1.73 m(2) per year) was 0.2 ml/min in patients without acute kidney injury, 0.8 ml/min following mild injury, and 2.8 ml/min following moderate to severe acute kidney injury. Thus, acute kidney injury following coronary angiography is associated with a sustained loss and a larger rate of future decline in kidney function.

Development and validation of a surname list to define Chinese ethnicity.

Background—Contrast-induced acute kidney injury (CI-AKI) has been associated with mortality, although it has been suggested this association may be attributable to confounding. We performed a systematic review and meta-analysis to characterize the associations between CI-AKI and subsequent clinical outcomes. Methods and Results—We identified studies using MEDLINE (1950 to June 2011) and Embase (1980 to June 2011), manual bibliographic searches, and contact with experts. We included observational studies that characterized outcomes among patients with and without AKI (based on changes in serum creatinine) after coronary angiography. Eligible studies reported at least 1 of mortality, cardiovascular events, end-stage renal disease, or length of hospital stay. Thirty-nine observational studies met inclusion criteria. Of 34 studies reporting mortality (including 139 603 participants), 33 reported an increased risk of death in those with CI-AKI, although the effect size varied between studies (I2=93.5%). Between-study heterogeneity was partially explained by whether adjustment for confounding features was performed (11 studies without adjustment; pooled crude risk ratio, 8.19; 95% confidence interval, 4.30–15.60; I2=77.3% versus 23 studies with adjustment; pooled adjusted risk ratio, 2.39; 95% confidence interval, 1.98–2.90; I2=88.3%). CI-AKI was consistently associated with an increased risk of cardiovascular events in 14 studies, end-stage renal disease in 3 studies, and prolonged hospitalization in 11 studies. Conclusions—CI-AKI is associated with an increased risk of mortality, cardiovascular events, renal failure, and prolonged hospitalization. However, the association between CI-AKI and mortality is strongly confounded by baseline clinical characteristics that simultaneously predispose to both kidney injury and mortality, and the risk attributable to CI-AKI is much lower than that reported from unadjusted studies.

Effect of short-term prostacyclin administration on restenosis after percutaneous transluminal coronary angioplasty☆

The problem of missing data is frequently encountered in observational studies. We compared approaches to dealing with missing data. Three multiple imputation methods were compared with a method of enhancing a clinical database through merging with administrative data. The clinical database used for comparison contained information collected from 6,065 cardiac care patients in 1995 in the province of Alberta, Canada. The effectiveness of the different strategies was evaluated using measures of discrimination and goodness of fit for the 1995 data. The strategies were further evaluated by examining how well the models predicted outcomes in data collected from patients in 1996. In general, the different methods produced similar results, with one of the multiple imputation methods demonstrating a slight advantage. It is concluded that the choice of missing data strategy should be guided by statistical expertise and data resources.