Heart Failure With Preserved Ejection Fraction
Patient data were obtained from the Duke Databank for Cardiovascular Disease (DDCD), an ongoing databank of all patients undergoing diagnostic cardiac catheterization at Duke University Medical Center. Patients were included in the study population if they underwent coronary angiography from January 2000 through December 2010, and if they had HFpEF and a history of ≥50% stenosis in at least 1 epicardial coronary vessel (only those patients with a history of significant coronary artery disease receive DDCD follow-up). Coronary stenoses were graded by visual consensus of at least 2 experienced observers. Patients were defined as having HFpEF if they had New York Heart Association (NYHA) functional class II to IV symptoms in the 2 weeks before index catheterization and EF ≥50%. Patients were excluded from analysis if they had EF <50%, unknown EF, unknown NYHA functional class, primary valvular heart disease (defined as moderate or severe aortic or mitral insufficiency, or severe stenosis of any heart valve), congenital heart disease, acquired immunodeficiency syndrome, or metastatic cancer.
Data from the index catheterization were prospectively collected as part of routine patient care. Baseline clinical variables for each patient were stored in the DDCD using methods previously described. Follow-up was obtained through self-administered questionnaires, with telephone follow-up to nonresponders. Patients not contacted through this mechanism had vital status determined through a search of the National Death Index.
AP classification was based on physician-obtained patient history just before cardiac catheterization and was defined as chest pain within the previous 6 weeks. Because many groups (e.g., women, elderly patients) present with atypical angina, we did not want to bias our results by using a classic angina definition alone. Given the prognostic value of angina characteristics, the severity, frequency, and pattern of occurrence were recorded at baseline. Revascularization was defined as treatment with percutaneous coronary intervention or coronary artery bypass graft. Death, myocardial infarction (MI), stroke, and cardiovascular rehospitalization were determined using methods previously described.
Baseline characteristics are described with medians and interquartile ranges (IQRs) for continuous variables and percentages for discrete variables in HFpEF patients with versus without AP. These characteristics were compared using the Wilcoxon rank sum test for continuous variables and chi-square tests for categorical variables unless otherwise noted. The primary endpoint was death/MI/revascularization/stroke (i.e., major adverse cardiac events [MACE]) and secondary endpoints were death/MI/revascularization, death/MI/stroke, death/MI, death, and cardiovascular death/cardiovascular hospitalization. Multivariable Cox proportional hazards regression analysis was used to adjust for baseline differences between groups. A comprehensive set of covariates was used for the adjustment analysis (see Table 3 footnote) based on clinical relevance and data from a previous investigation. With the large number of events in each analysis, there was no overfitting problem with adjustment variables. Adjusted time-to-event results were generated for the endpoints, and comparisons were made using the log-rank test. A p value of <0.05 was used to indicate statistical significance for all comparisons. Statistical analyses were performed by Duke Clinical Research Institute (Durham, North Carolina) using SAS (version 9.2, SAS Institute, Cary, North Carolina). The protocol was approved by the institutional review board at Duke University, and all patients voluntarily provided written informed consent.
Methods
Patient data were obtained from the Duke Databank for Cardiovascular Disease (DDCD), an ongoing databank of all patients undergoing diagnostic cardiac catheterization at Duke University Medical Center. Patients were included in the study population if they underwent coronary angiography from January 2000 through December 2010, and if they had HFpEF and a history of ≥50% stenosis in at least 1 epicardial coronary vessel (only those patients with a history of significant coronary artery disease receive DDCD follow-up). Coronary stenoses were graded by visual consensus of at least 2 experienced observers. Patients were defined as having HFpEF if they had New York Heart Association (NYHA) functional class II to IV symptoms in the 2 weeks before index catheterization and EF ≥50%. Patients were excluded from analysis if they had EF <50%, unknown EF, unknown NYHA functional class, primary valvular heart disease (defined as moderate or severe aortic or mitral insufficiency, or severe stenosis of any heart valve), congenital heart disease, acquired immunodeficiency syndrome, or metastatic cancer.
Data from the index catheterization were prospectively collected as part of routine patient care. Baseline clinical variables for each patient were stored in the DDCD using methods previously described. Follow-up was obtained through self-administered questionnaires, with telephone follow-up to nonresponders. Patients not contacted through this mechanism had vital status determined through a search of the National Death Index.
AP classification was based on physician-obtained patient history just before cardiac catheterization and was defined as chest pain within the previous 6 weeks. Because many groups (e.g., women, elderly patients) present with atypical angina, we did not want to bias our results by using a classic angina definition alone. Given the prognostic value of angina characteristics, the severity, frequency, and pattern of occurrence were recorded at baseline. Revascularization was defined as treatment with percutaneous coronary intervention or coronary artery bypass graft. Death, myocardial infarction (MI), stroke, and cardiovascular rehospitalization were determined using methods previously described.
Statistical Analysis
Baseline characteristics are described with medians and interquartile ranges (IQRs) for continuous variables and percentages for discrete variables in HFpEF patients with versus without AP. These characteristics were compared using the Wilcoxon rank sum test for continuous variables and chi-square tests for categorical variables unless otherwise noted. The primary endpoint was death/MI/revascularization/stroke (i.e., major adverse cardiac events [MACE]) and secondary endpoints were death/MI/revascularization, death/MI/stroke, death/MI, death, and cardiovascular death/cardiovascular hospitalization. Multivariable Cox proportional hazards regression analysis was used to adjust for baseline differences between groups. A comprehensive set of covariates was used for the adjustment analysis (see Table 3 footnote) based on clinical relevance and data from a previous investigation. With the large number of events in each analysis, there was no overfitting problem with adjustment variables. Adjusted time-to-event results were generated for the endpoints, and comparisons were made using the log-rank test. A p value of <0.05 was used to indicate statistical significance for all comparisons. Statistical analyses were performed by Duke Clinical Research Institute (Durham, North Carolina) using SAS (version 9.2, SAS Institute, Cary, North Carolina). The protocol was approved by the institutional review board at Duke University, and all patients voluntarily provided written informed consent.
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