Knowledge of left ventricular ejection fraction. Measurement of Ejection Fraction After Myocardial Infarction in the Population*

Transcription

1 Measurement of Ejection Fraction After Myocardial Infarction in the Population* Francisco Lopez-Jimenez, MD, MSc; Tauqir Y. Goraya, MD, PhD; Jens P. Hellermann, MD; Steven J. Jacobsen, MD, PhD; Guy S. Reeder, MD; Susan A. Weston, MS; and Véronique L. Roger, MD, MPH Objectives: To assess the secular trends in left ventricular ejection fraction (LVEF) assessment after myocardial infarction (MI) and to identify the determinants of testing. Design: A population-based MI incidence cohort. Methods: The use of tests measuring LVEF (echocardiography, radionuclide, and left ventricular [LV] angiography) was examined among all consecutive residents of Olmsted County, MN, hospitalized for a validated incident MI between 1979 and Baseline characteristics and outcome were ascertained from community medical records. Results: Among 2,317 patients with incident MI, LVEF assessment increased from 1979 to 1986 (22 to 85%; p value for trend ) to stabilize thereafter until During the most recent decade, LVEF was measured during the hospital stay in 81% of the patients. Characteristics associated with lesser use of tests included older age and measurement of ejection fraction within 1 year prior to the index MI. Larger MI size, prolonged hospital stay, and involvement of a cardiologist as a care provider were positively associated with determination of LVEF. Conclusions: Measurement of LVEF after MI increased in the last 2 decades, but there continues to be a group of patients in whom it is not done. Given the potential benefits of LVEF measurement, including knowledge for risk stratification and therapeutic choices as underscored in recent practice guidelines, there may be additional opportunities for improving outcomes by ensuring its more consistent use. However, as testing for LVEF differs according to patient characteristics, reliance on selected clinically performed LVEF measurements will result in biased estimates of the prevalence of LV dysfunction after MI. (CHEST 2004; 125: ) Key words: ejection fraction; left ventricular function; myocardial infarction Abbreviations: ACC American College of Cardiology; ACE angiotensin-converting enzyme; AHA American Heart Association; CI confidence interval; CK creatine kinase; EF ejection fraction; LV left ventricular; LVEF left ventricular ejection fraction; MI myocardial infarction Knowledge of left ventricular ejection fraction (LVEF) after acute myocardial infarction (MI) helps stratify risk 1 3 and guides the use of evidence- *From the Department of Health Sciences Research (Dr. Jacobsen and Ms. Weston), Division of Cardiovascular Diseases and Internal Medicine (Drs. Lopez-Jimenez, Reeder, and Roger), Mayo Clinic and Foundation, Rochester, MN; Michigan Heart & Vascular Institute (Dr. Goraya), St. Joseph Mercy Hospital, Ann Arbor, MI; and University Hospital Zurich (Dr. Hellermann), Zurich, Switzerland. Supported in part by grants from the Public Health Service and the National Institutes of Health (AR30582 and RO1 HL 59205). Dr. Roger is an Established Investigator of the American Heart Association. Manuscript received March 18, 2003; revision accepted July 8, Reproduction of this article is prohibited without written permission from the American College of Chest Physicians ( permissions@chestnet.org). Correspondence to: Véronique L. Roger, MD, MPH, Division of Cardiovascular Diseases, Mayo Clinic, 200 First St SW, Rochester, MN 55905; roger.veronique@mayo.edu based treatment such as angiotensin-converting enzyme (ACE) inhibitors and -blockers and revascularization. 4,5 Indeed, studies 6,7 demonstrated positive associations between LVEF measurement and use of ACE inhibitor therapy after MI. Furthermore, data 8 10 underscore the pivotal role of LVEF in the selection of candidates for an automatic implantable cardioverter-defibrillator. Within this framework, current guidelines for the management of patients with MI emphasized the importance of LVEF assessment before discharge, 11,12 and the report of American Heart Association(AHA)/American College of Cardiology (ACC) Conference on the Assessment of Healthcare Quality in Cardiovascular Disease and Stroke 13 underscored the need to monitor LVEF measurement among patients with MI as a quality-of-care indicator. In contrast with the evidence supporting LVEF CHEST / 125 / 2/ FEBRUARY,

2 measurement after MI, little is known about actual utilization rates of tests to do so, how it may have evolved over time, and what determines its use in practice. 14,15 The present study was undertaken to address these gaps in knowledge and assess the trends in the use of testing for LVEF after an incident MI in Olmsted County between 1979 and Study Setting Materials and Methods This study was carried out within the boundaries of Olmsted County, MN. Epidemiologic research in the county is possible because it is relatively isolated from other urban centers, and nearly all medical care is delivered to local residents by few providers. With the exception of a higher proportion of the working population employed in the health-care industry, the characteristics of the population of Olmsted County are similar to those of US whites. The Mayo Clinic provides approximately half of the primary care and nearly all specialty care for the community. Olmsted Medical Center and its affiliated hospital, along with the Mayo Clinic, provide comprehensive care for the region in every discipline. The epidemiologic potential in the community is enhanced by the fact that each provider uses a comprehensive medical record system, whereby all data collected on an individual are assembled in one place. Thus, the details of every inpatient and outpatient encounter can be accessed. Data are easily retrievable because the Mayo Clinic has maintained since the early 1900s extensive indexes based on clinical and histologic diagnoses and surgical procedures. Since 1966, similar indexes have been developed for non-mayo providers under the aegis of the Rochester Epidemiology Project. This linkage system thus constitutes a unique opportunity to ensure complete ascertainment of tests in defined disease processes. Data Collection The procedures used to assemble the MI incidence cohort have been reported in detail elsewhere. 16,17 Briefly, all incident MIs between 1979 and 1998 were ascertained from indexes of medical diagnosis and hospital discharges using standardized epidemiologic criteria, 18 relying on cardiac pain, creatine phosphokinase enzyme values, and Minnesota coding of the ECG. Baseline Characteristics and End Point Definitions and Ascertainment Because of the change over time in the normal values and corresponding ranges, peak creatine kinase (CK) was defined as twice the upper limit of normal for each unit in use within a corresponding time frame. Comorbidity was measured using the Charlson index. 19,20 Reperfusion therapy was defined as thrombolysis or coronary angioplasty within 24 h after symptom onset. History of smoking was analyzed while combining former and current smoking. Clinician s diagnoses were used to ascertain hyperlipidemia, hypertension, and diabetes mellitus. The use of inpatient and outpatient tests for measurement of LVEF was ascertained by electronic queries of the databases of the echocardiography and nuclear cardiology laboratory databases for the entire study period and of the cardiac catheterization database beginning in A manual search of the catheterization laboratory database was performed for the years prior to Statistical Analysis The Mantel-Haenszel 2 test for trend was used to analyze the change in the proportion of patients tested for LVEF over time, and the Pearson 2 test was used to compare proportions. Logistic regression was used to examine the independent association between demographic and clinical variables, and testing for LVEF within 30 days after index MI. Candidate predictor variables included age, sex, testing for LVEF within 1 year prior to incident MI, history of congestive heart failure before the index MI, diabetes mellitus, hypertension, comorbidity, peak CK ratio, evaluation by a cardiologist, use of reperfusion therapy, length of hospital stay 10 days, and year of the MI. Interactions between age and year of the MI and sex and year of the MI were examined. Cox proportional hazards models were constructed to examine the association between LVEF evaluation and mortality. Results of the final models were summarized by presenting the relative risk and 95% confidence intervals (CIs). A p value of 0.05 was selected for the threshold of statistical significance except for interaction testing, when values up to 0.10 were accepted. Analyses were performed using SAS version 8.2 (SAS Institute; Cary, NC) and S-Plus Version (Insightful Corporation; Lucent Technologies; Seattle, WA). The study was approved by the Mayo Foundation Institutional Review Board. Results Time Trends of Testing To Measure LVEF After MI Between 1979 and 1998, 2,317 subjects in Olmsted County were hospitalized with an incident MI. The percentage of patients undergoing testing for LVEF within 30 days after MI over time is shown in Figure 1. The use of testing increased from 22% in 1979 to 85% by 1986 (p value for trend ) and stabilized thereafter. The distribution of use of individual tests (Fig 1) indicates that the use of radionuclide angiography peaked at 44% in 1985 and declined sharply thereafter. Use of contrast left ventriculography increased from 10% in 1979 to 58% in 1988 and declined somewhat in the more recent years. Use of transthoracic echocardiography for measurement of LVEF increased from 14% in 1979 to 65% in 1986 and stabilized thereafter. Between 1979 and 1987, 49% of the total number of patients with MI underwent testing to measure LVEF within the first 10 days after MI, with 52% prior to hospital dismissal. Between 1988 and 1998, 81% of the total number of patients with MI underwent testing to measure LVEF within the first 10 days after MI, with 81% prior to hospital dismissal. In 90% of the cases, a cardiologist was either the primary caregiver (83%) or served as a consulting physician (7%). Thus, only a small component of the cohort was not evaluated by a cardiologist (10%). As the utilization of tests to measure LVEF stabilized in the last decade, the rest of the analysis focused on the period 1988 to 1998 to determine the contemporary determinants of LVEF measurements. 398 Clinical Investigations

3 Figure 1. Time trends in the assessment of LVEF within 30 days of incident MI, 1979 to pts patients. Characteristics Associated With Testing To Measure LVEF Table 1 compares the characteristics of patients who underwent measurement of LVEF within 30 days after an incident MI between 1988 and 1998 to those who did not. Characteristics associated with greater likelihood of ejection fraction (EF) measurement included male sex, higher peak CK, cardiologist involved as a care provider during the index hospitalization, and length of hospital stay 10 days. Characteristics associated with lesser likelihood of EF measurement included older age, greater comorbidity, measurement of EF within 1 year prior to the MI, and history of heart failure. There was no difference between the two groups with regards to prior history of diabetes, hypertension, or reperfusion therapy. When characteristics univariately associated with EF measurement were entered in a multivariable model, EF measurement prior to index MI was independently associated with lesser use of tests to measure LVEF after the index MI (Table 2). Involvement of a cardiologist as a care provider during the index hospitalization and higher peak CK were independently associated with greater use of tests to measure LVEF. With regards to age, use of tests to measure LVEF was the greatest among persons in the age group of 60 to 74 years and less frequent above the age of 75 years. There was no independent association between male sex, history of heart failure and comorbidity, and LVEF measurement. These associations did not change after adding reperfusion therapy in the models, and there was no interaction between year and age and year and sex. Survival After adjusting for comorbidities and for other determinants of LVEF testing (including age, sex, year, peak CK, history of heart failure and comorbidity, EF measurement prior to index MI, cardiologist involved as care provider, length of stay 10 days and reperfusion), patients who did not have an assessment of LVEF within 30 days of the index MI had an increased mortality during follow-up (relative risk of death if EF not measured, 1.69; 95% CI, 1.36 to 2.10). Discussion The results presented herein indicate that measurement of LVEF after MI increased over time but was not measured in approximately 20% of the patients with MI within the last decade of the study period. The involvement of a cardiologist in the care of the patient was a strong independent predictor of CHEST / 125 / 2/ FEBRUARY,

4 Table 1 Baseline Characteristics by LVEF Assessment Within 30 Days of Incident MI Occurring Between 1988 and 1998* Characteristics LVEF Not Measured (n 238) LVEF Measured (n 1,124) Odds Ratio (95% CI) p Value Years ( ) ( ) Age, yr ( ) At least ( ) Male gender ( ) CK First tertile Second tertile ( ) Third tertile ( ) Trauma ( ) LVEF measured within 1 yr ( ) prior to index MI Comorbidity None ( ) ( ) Diabetes mellitus ( ) 0.68 Hypertension ( ) 0.54 Heart failure ( ) Cardiologist involved in care ( ) Use of reperfusion therapy ( ) 0.63 Length of stay 10 d ( ) *Data are presented as % unless otherwise indicated. LVEF measurement, which was also more likely to occur in the case of larger infarctions as reflected by higher peak CK values and when the hospital stay was prolonged. Thus, within the last decade of the study period, testing for LVEF was not used uniformly in acute MI, a practice that may impact risk stratification and utilization of evidence-based medications after MI. Additionally, as testing for LVEF differs according to patient characteristics, reliance on clinical assessment of EF will result in biased estimates of the prevalence of left ventricular (LV) systolic dysfunction after MI and of outcomes. Current Recommendations While some studies 21,22 reported that an approximate estimation of LVEF can be performed clinically in 40% of patients after MI, the practical value of such scoring systems is limited. Indeed, studies 23,24 reported associations between several clinical indicators and abnormal LVEF, but these studies consisted of relatively small case series and the proposed prediction algorithms were not validated independently. In the current guidelines for the management of patients with acute MI, the ACC and AHA strongly support the measurement of LVEF after MI and underscore the value of predischarge assessment of ventricular function for risk stratification. 12 Actual Frequency of LVEF Measurement After MI Little is know about the use of tests to measure LV function after MI in practice and how this may have evolved over time. In a recent report from the Cooperative Cardiovascular Project, LVEF measurements were missing in 30% of the patients who survived hospitalization for a confirmed MI in the period 1994 to 1995 in acute-care hospitals in the United States. 25 These data are consistent with data from a study of Medicare beneficiaries hospitalized in the period 1992 to 1993 and among whom LVEF was measured before discharge in 65% of the patients. 14 The results presented herein extend previously reported findings 14,25 by indicating that during the last 20 years, the use of tests to measure LVEF increased dramatically during the first decade characterized by rapid incorporation of new technology in practice. Its use, however, stabilized over the last decade. Thus, the use of testing to measure LVEF 400 Clinical Investigations

5 Table 2 Independent Predictors of LVEF Assessment Within 30 Days of Incident MI Occurring Between 1988 and 1998 Characteristics Odds Ratio (95% CI) p Value Years ( ) ( ) Age, yr ( ) At least ( ) Male gender 1.33 ( ) CK First tertile 1 Second tertile 1.05 ( ) Third tertile 1.51 ( ) Trauma 1.00 ( ) Comorbidity 0.62 None ( ) ( ) History of heart failure 0.71 ( ) 0.15 EF within 1 yr prior to MI 0.40 ( ) Cardiologist involved in care 3.06 ( ) Length of stay 10 d 4.9 ( ) did not increase appreciably since the publication of the aforementioned reports. 14,25 Furthermore, only 80% of patients underwent LVEF measurement during hospital stay, which is the optimal time to make use of the information on LVEF to optimize the use of evidence-based therapies after MI. The present results indicate that factors associated with determination of LVEF after MI were large MI size as measured with CK, prolonged hospital stay, and cardiologist involved in the delivery of care. Conversely, age 75 years and greater degree of comorbidities were associated with less likelihood of LVEF determination. These findings support and extend previously reported associations between determination of LVEF and patient characteristics. 14 In particular, the present study underscores the role of older age ( 75 years) as a barrier to measurement of LVEF. The negative association between LVEF determination and age are of particular concern given the shift of the burden of MI toward the elderly, 17 who constitute an increasingly large component of MI subjects. Recent data 26 underscored the association between the specialty of the ambulatory physician and the delivery of care among MI survivors. The present study extends these findings by demonstrating a positive association between the involvement of a cardiologist as a care provider and the measurements of LVEF among all consecutive patients from a geographically defined population admitted with acute MI irrespective of their hospital outcomes, such that the results are generalizable to all MI patients, not only survivors. Implications The ascertainment of LVEF after MI enhances risk stratification and optimizes the use of evidencebased therapies. With regards to risk stratification, assessment of LV function helps predict cardiac events after MI in both the before-reperfusion 27 and reperfusion eras. 28 To this end, as reported in the experience of the present group and others, the EF provides information incremental to that of commonly used post-mi risk stratification approaches, 3,25 and its value is underscored in the 1999 updated ACC/AHA guidelines for the management of patients with acute MI. 12 Knowledge of LVEF is associated with more frequent use of ACE inhibitors after MI, 14 and may contribute to increase the use of -blockers, which is currently not optimal. 29 To this end, the frequency of the measurement of LVEF after MI has been considered as a process-of-care quality-performance measure, 30 an approach supported by the present data. An ancillary survival analysis indicated that patients without LVEF assessment had worse survival. As in any observational study, residual confounding may account for this association. However, this underscores that the use of clinically indicated tests to measure the prevalence of LV dysfunction after MI and/or to ascertain outcomes is confounded by indication and will likely provide biased estimates. Indeed, estimates of the true prevalence of LV systolic dysfunction vary depending on the value of LV function in the group in whom it was not measured. To this end, we reported that the proportion of patients with preserved LVEF after MI among subjects with post-mi heart failure could vary notably, 31 depending on assumptions for LVEF among patients without LV function measured. These results provide important insights into the patterns of practice with regards to measurements of EF after MI. Potential limitations should be kept in mind, however, while interpreting the data. The indications for measuring LVEF by noninvasive and invasive methods are different. The purpose of this article was to report on the use of all tests in order to ascertain the frequency with which the information is available for decision making regarding the use of evidence-based therapies in MI. Thus, the respective indications for the use of each method are beyond the scope of this report and were not addressed. While routine assessment of LVEF may be chal- CHEST / 125 / 2/ FEBRUARY,

6 lenged in subjects with minimal myocardial damage as determined by novel biomarkers, our findings apply to MIs ascertained using CK/CK-MB only, as troponin was not used in Olmsted County at that time. The racial and ethnic composition of Olmsted County is becoming more diverse, 32 but during the study period more limited diversity may limit the generalization of these data to groups underrepresented in the population. Conversely, however, the quasi totality of the population has some form of health insurance such that confounding by access to care is unlikely to explain the present results. 33 Conclusion Measurement of LVEF after MI increased the last 2 decades, but there continues to be a group of patients in whom it is not done. 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