Ronald J. Krone

Contemporary mortality risk prediction for percutaneous coronary intervention: results from 588,398 procedures in the National Cardiovascular Data Registry.

OBJECTIVES We sought to create contemporary models for predicting mortality risk following percutaneous coronary intervention (PCI). BACKGROUND There is a need to identify PCI risk factors and accurately quantify procedural risks to facilitate comparative effectiveness research, provider comparisons, and informed patient decision making. METHODS Data from 181,775 procedures performed from January 2004 to March 2006 were used to develop risk models based on pre-procedural and/or angiographic factors using logistic regression. These models were independently evaluated in 2 validation cohorts: contemporary (n = 121,183, January 2004 to March 2006) and prospective (n = 285,440, March 2006 to March 2007). RESULTS Overall, PCI in-hospital mortality was 1.27%, ranging from 0.65% in elective PCI to 4.81% in ST-segment elevation myocardial infarction patients. Multiple pre-procedural clinical factors were significantly associated with in-hospital mortality. Angiographic variables provided only modest incremental information to pre-procedural risk assessments. The overall National Cardiovascular Data Registry (NCDR) model, as well as a simplified NCDR risk score (based on 8 key pre-procedure factors), had excellent discrimination (c-index: 0.93 and 0.91, respectively). Discrimination and calibration of both risk tools were retained among specific patient subgroups, in the validation samples, and when used to estimate 30-day mortality rates among Medicare patients. CONCLUSIONS Risks for early mortality following PCI can be accurately predicted in contemporary practice. Incorporation of such risk tools should facilitate research, clinical decisions, and policy applications.

Appropriateness of Percutaneous Coronary Intervention

CONTEXT Despite the widespread use of percutaneous coronary intervention (PCI), the appropriateness of these procedures in contemporary practice is unknown. OBJECTIVE To assess the appropriateness of PCI in the United States. DESIGN, SETTING, AND PATIENTS Multicenter, prospective study of patients within the National Cardiovascular Data Registry undergoing PCI between July 1, 2009, and September 30, 2010, at 1091 US hospitals. The appropriateness of PCI was adjudicated using the appropriate use criteria for coronary revascularization. Results were stratified by whether the procedure was performed for an acute (ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, or unstable angina with high-risk features) or nonacute indication. MAIN OUTCOME MEASURES Proportion of acute and nonacute PCIs classified as appropriate, uncertain, or inappropriate; extent of hospital-level variation in inappropriate procedures. RESULTS Of 500,154 PCIs, 355,417 (71.1%) were for acute indications (ST-segment elevation myocardial infarction, 103,245 [20.6%]; non-ST-segment elevation myocardial infarction, 105,708 [21.1%]; high-risk unstable angina, 146,464 [29.3%]), and 144,737 (28.9%) for nonacute indications. For acute indications, 350,469 PCIs (98.6%) were classified as appropriate, 1055 (0.3%) as uncertain, and 3893 (1.1%) as inappropriate. For nonacute indications, 72,911 PCIs (50.4%) were classified as appropriate, 54,988 (38.0%) as uncertain, and 16,838 (11.6%) as inappropriate. The majority of inappropriate PCIs for nonacute indications were performed in patients with no angina (53.8%), low-risk ischemia on noninvasive stress testing (71.6%), or suboptimal (≤1 medication) antianginal therapy (95.8%). Furthermore, although variation in the proportion of inappropriate PCI across hospitals was minimal for acute procedures, there was substantial hospital variation for nonacute procedures (median hospital rate for inappropriate PCI, 10.8%; interquartile range, 6.0%-16.7%). CONCLUSIONS In this large contemporary US cohort, nearly all acute PCIs were classified as appropriate. For nonacute indications, however, 12% were classified as inappropriate, with substantial variation across hospitals.

A contemporary overview of percutaneous coronary interventions: The American College of Cardiology–National Cardiovascular Data Registry (ACC–NCDR)

The American College of Cardiology (ACC) established the National Cardiovascular Data Registry (ACC-NCDR) to provide a uniform and comprehensive database for analysis of cardiovascular procedures across the country. The initial focus has been the high-volume, high-profile procedures of diagnostic cardiac catheterization and percutaneous coronary intervention (PCI). Several large-scale multicenter efforts have evaluated diagnostic catheterization and PCI, but these have been limited by lack of standard definitions and relatively nonuniform data collection and reporting methods. Both clinical and procedural data, and adverse events occurring up to hospital discharge, were collected and reported according to uniform guidelines using a standard set of 143 data elements. Datasets were transmitted quarterly to a central facility for quality-control screening, storage and analysis. This report is based on PCI data collected from January 1, 1998, through September 30, 2000.A total of 139 hospitals submitted data on 146,907 PCI procedures. Of these, 32% (46,615 procedures) were excluded because data did not pass quality-control screening. The remaining 100,292 procedures (68%) were included in the analysis set. Average age was 64 +/- 12 years; 34% were women, 26% had diabetes mellitus, 29% had histories of prior myocardial infarction (MI), 32% had prior PCI and 19% had prior coronary bypass surgery. In 10% the indication for PCI was acute MI < or =6 h from onset, while in 52% it was class II to IV or unstable angina. Only 5% of procedures did not have a class I indication by ACC criteria, but this varied by hospital from a low of 0 to a high of 38%. A coronary stent was placed in 77% of procedures, but this varied by hospital from a low of 0 to a high of 97%. The frequencies of in-hospital Q-wave MI, coronary artery bypass graft surgery and death were 0.4%, 1.9% and 1.4%, respectively. Mortality varied by hospital from a low of 0 to a high of 4.2%. This report presents the first data collected and analyzed by the ACC-NCDR. It portrays a contemporary overview of coronary interventional practices and outcomes, using uniform data collection and reporting standards. These data reconfirm overall acceptable results that are consistent with other reported data, but also confirm large variations between individual institutions.

Impact of ethnicity and gender differences on angiographic coronary artery disease prevalence and in-hospital mortality in the American College of Cardiology-National Cardiovascular Data Registry.

Background— Although populations referred for coronary angiography are increasingly diverse, there is limited information on coronary artery disease (CAD) prevalence and in-hospital mortality other than for predominately white male patients. Methods and Results— We examined gender and ethnic differences in CAD prevalence and in-hospital mortality in a prospective cohort of patients referred for angiographic evaluation of stable angina (n=375 886) or acute coronary syndromes (ACS; unstable angina or myocardial infarction, n=450 329) at 388 US hospitals participating in the American College of Cardiology–National Cardiovascular Data Registry, an angiographic registry. Univariable and multivariable (with covariates that included risk factors, symptoms, and comorbidities) logistic regression models were used to estimate significant CAD, defined as ≥70% stenosis, and in-hospital mortality. Within stable angina and ACS cohorts, 7% of patients were black, 2% were Hispanic, 0.3% were Native American, 1% were Asian, and 90% were white, respectively. In stable angina, the risk-adjusted OR for significant CAD was 0.34 for women compared with men (P<0.0001), with black women having the lowest risk-adjusted odds (P<0.0001) compared with other females. Among ACS patients, the risk-adjusted OR of significant CAD was 0.47 for women compared with men (P<0.0001); similarly, black women had the lowest risk-adjusted odds (P<0.0001) compared with other females. Higher in-hospital mortality was reported for white women presenting with stable angina (P<0.00001). White women had a 1.34-fold (95% CI 1.21 to 1.48) higher risk-adjusted odds ratio for mortality than white men with stable angina (P<0.0001), with higher rates noted for white women who were older or had significant CAD (both P<0.0001). Lower utilization of elective coronary revascularization, aspirin, and glycoprotein IIb/IIIa inhibitors (all P<0.0001) may have contributed to higher in-hospital mortality for white women. In ACS, higher in-hospital mortality was reported for Hispanic (P=0.015) and white (P<0.0001) women; however, neither white (P=0.51) or Hispanic (P=0.13) women had higher in-hospital risk-adjusted mortality. Conclusions— The likelihood for significant CAD at coronary angiography and for in-hospital mortality varied significantly by ethnicity and gender. Future clinical practice guidelines should be tailored to gender subsets of the population, in particular for black women, to improve the efficient use of angiographic laboratories and to target at-risk populations of women and men.

Coronary Revascularization in Diabetic Patients A Comparison of the Randomized and Observational Components of the Bypass Angioplasty Revascularization Investigation (BARI)

BACKGROUND Patients with treated diabetes in the randomized-trial segment of the Bypass Angioplasty Revascularization Investigation (BARI) who were randomized to initial revascularization with PTCA had significantly worse 5-year survival than patients assigned to CABG. This treatment difference was not seen among diabetic patients eligible for BARI who opted to select their mode of revascularization. We hypothesized that differences in patient characteristics, assessed and unmeasured, together with the treatment selection in the registry, at least partially account for this discrepancy. METHODS AND RESULTS Among diabetics taking insulin or oral hypoglycemic drugs at entry, angiographic and clinical presentations were comparable between randomized and registry patients. However, more registry patients were white, and registry diabetics tended to be more educated and more physically active and to report better quality of life. Procedural characteristics and in-hospital complications were comparable. The 5-year all-cause mortality rate was 34.5% in randomized diabetic patients assigned to PTCA versus 19.4% in CABG patients (P=0.0024; relative risk [RR]=1.87); corresponding cardiac mortality rates were 23.4% and 8.2%, respectively (P=0.0002; RR=3.10). The CABG benefit was more apparent among patients requiring insulin. In the registry, all-cause mortality was 14.4% for PTCA versus 14.9% for CABG (P=0.86, RR=1.10), with corresponding cardiac mortality rates of 7.5% and 6. 0%, respectively (P=0.73; RR=1.07). These RRs in the registry increased to 1.29 and 1.41, respectively, after adjustment for all known differences between treatment groups. CONCLUSIONS BARI registry results are not inconsistent with the finding in the randomized trial that initial CABG is associated with better long-term survival than PTCA in treated diabetic patients with multivessel coronary disease suitable for either surgical or catheter-based revascularization.

Thrombogenic Factors and Recurrent Coronary Events

BACKGROUND Thrombosis is a pivotal event in the pathogenesis of coronary disease. We hypothesized that the presence of blood factors that reflect enhanced thrombogenic activity would be associated with an increased risk of recurrent coronary events during long-term follow-up of patients who have recovered from myocardial infarction. METHODS AND RESULTS We prospectively enrolled 1045 patients 2 months after an index myocardial infarction. Baseline thrombogenic blood tests included 6 hemostatic variables (D-dimer, fibrinogen, factor VII, factor VIIa, von Willebrand factor, and plasminogen activator inhibitor-1), 7 lipid factors [cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, lipoprotein(a), apolipoprotein (apo)A-I, and apoB], and insulin. Patients were followed up for an average of 26 months, with the primary end point being coronary death or nonfatal myocardial infarction, whichever occurred first. The hemostatic, lipid, and insulin parameters were dichotomized into their top and the lower 3 risk quartiles and evaluated for entry into a Cox survivorship model. High levels of D-dimer (hazard ratio, 2.43; 95% CI, 1.49, 3.97) and apoB (hazard ratio, 1.82; 95% CI, 1.10, 3.00) and low levels of apoA-I (hazard ratio, 1.84; 95% CI, 1.10, 3.08) were independently associated with recurrent coronary events in the Cox model after adjustment for 6 relevant clinical covariates. CONCLUSIONS Our findings indicate that a procoagulant state, as reflected in elevated levels of D-dimer, and disordered lipid transport, as indicated by low apoA-1 and high apoB levels, contribute independently to recurrent coronary events in postinfarction patients.

Development of a risk adjustment mortality model using the American College of Cardiology–National Cardiovascular Data Registry (ACC–NCDR) experience: 1998–2000

OBJECTIVES We sought to develop and evaluate a risk adjustment model for in-hospital mortality following percutaneous coronary intervention (PCI) procedures using data from a large, multi-center registry. BACKGROUND The 1998-2000 American College of Cardiology-National Cardiovascular Data Registry (ACC-NCDR) dataset was used to overcome limitations of prior risk-adjustment analyses. METHODS Data on 100,253 PCI procedures collected at the ACC-NCDR between January 1, 1998, and September 30, 2000, were analyzed. A training set/test set approach was used. Separate models were developed for presentation with and without acute myocardial infarction (MI) within 24 h. RESULTS Factors associated with increased risk of PCI mortality (with odds ratios in parentheses) included cardiogenic shock (8.49), increasing age (2.61 to 11.25), salvage (13.38) urgent (1.78) or emergent PCI (5.75), pre-procedure intra-aortic balloon pump insertion (1.68), decreasing left ventricular ejection fraction (0.87 to 3.93), presentation with acute MI (1.31), diabetes (1.41), renal failure (3.04), chronic lung disease (1.33); treatment approaches including thrombolytic therapy (1.39) and non-stent devices (1.64); and lesion characteristics including left main (2.04), proximal left anterior descending disease (1.97) and Society for Cardiac Angiography and Interventions lesion classification (1.64 to 2.11). Overall, excellent discrimination was achieved (C-index = 0.89) and application of the model to high-risk patient groups demonstrated C-indexes exceeding 0.80. Patient factors were more predictive in the MI model, while lesion and procedural factors were more predictive in the analysis of non-MI patients. CONCLUSIONS A risk adjustment model for in-hospital mortality after PCI was successfully developed using a contemporary multi-center registry. This model is an important tool for valid comparison of in-hospital mortality after PCI.

Long-Term Clinical Outcome in the Bypass Angioplasty Revascularization Investigation Registry Comparison With the Randomized Trial

Background-The Bypass Angioplasty Revascularization Investigation (BARI) included 4039 patients with multivessel coronary artery disease; 1829 consented to randomization, and 2010 did not but were followed up in a registry. Thus, we can evaluate the outcome of physician-guided versus random assignment of percutaneous transluminal coronary angioplasty (PTCA) versus coronary artery bypass graft surgery (CABG). Methods and Results-We compared the baseline features and outcomes for PTCA and CABG in the overall registry and its predesignated subgroups. We assessed the impact of treatment by choice versus random assignment by comparing the results in the registry with those of the randomized trial. Statistical adjustments for differences in baseline characteristics were made. Within the registry, nearly twice as many patients were selected for PTCA (1189) as CABG (625); mortality at 7 years was similar for PTCA (13.9%) and CABG (14.2%) (P=0.66) before and after adjustment for baseline differences between patients selected for PTCA versus CABG (adjusted RR, 1.02; P=0.86). In contrast to the randomized trial, the 7-year mortality rate of treated diabetics in the registry was equally high (26%) with PTCA or CABG. Seven-year mortality was higher for patients undergoing PTCA in the randomized trial than in the registry (19.1% versus 13.9%, P<0.01) but not for those undergoing CABG (15.6% versus 14.2%, P=0.57). The adjusted relative mortality risk for PTCA in the randomized versus registry population was 1.17 (P=0.16). Conclusions-BARI physicians were able to select PTCA rather than CABG for 65% of registry patients who underwent revascularization without compromising long-term survival either in the overall population or in treated diabetics.

Low-level exercise testing after myocardial infarction: usefulness in enhancing clinical risk stratification.

Of 866 patients enrolled in our multicenter study, 667 performed a low-level exercise test early after myocardial infarction, most before discharge. Excluding seven patients who died before the test could be considered, there was a 14% 1 year cardiac mortality in 192 patients who did not take the test (150 for medical and 42 for logistic reasons) compared with 5% in those who did (p less than .0001). Of those who took the test, 12% subsequently underwent bypass grafts surgery compared with 14% of those who did not (p greater than .05). Decreased mortality in the year after the infarction in those taking the test was associated with an increase in blood pressure to 110 mm Hg or higher (3% vs 18%; p less than .001), ability to complete the 9 min test (3% vs 8%; p less than .01), and the absence of couplets (4% vs 13%; p less than .05) or any ventricular ectopic depolarizations (4% vs 7%, p less than .05) before, during, or after exercise. Achievement of a blood pressure of 110 mm Hg or higher during exercise in patients with no evidence of pulmonary congestion on the chest x-ray identified a group of 454 patients (70% of those taking the test) with a 1 year cardiac mortality of 1% compared with 13% in the remaining patients (p less than .0001). Logistic models showed that the exercise test contributed independent prognostic information for cardiac death, new infarction, and bypass surgery. Results of low-level exercise testing before hospital discharge combined with clinical features of the infarction can effectively identify patients at low risk for subsequent cardiac mortality.

Prevention of contrast induced nephropathy: Recommendations for the high risk patient undergoing cardiovascular procedures

Contrast induced nephropathy (CIN) is the third leading cause of hospital aquired renal failure and is associated with significant morbidity and mortality. Chronic kidney disease is the primary predisposing factor for CIN. As estimated glomerular filtration rate <60 ml/1.73 m2 represents significant renal dysfunction and defines patients at high risk. Modifiable risk factors for CIN include hydration status, the type and amount of contrast, use of concomitant nephrotoxic agents and recent contrast administration. The cornerstone of CIN prevention, in both the high and low risk patients, is adequate parenteral volume repletion. In the patient at increased risk for CIN it is often appropriate to withhold potentially nephrotoxic medications, and consider the use of n‐acetylcysteine. In patients at increased risk for CIN the use of low or iso‐osomolar contrast agents should be utilized and strategies employed to minimize contrast volume. In these patients serum creatinine should be obtained forty‐eight hours post procedure and it is often appropriate to continue withholding medications such as metformin or non steroidal anti‐inflammatories until renal function returns to normal.