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CARDIOVASCULAR ANESTHESIA

The Prevalence of Preoperative Diastolic Filling Abnormalities in Geriatric Surgical Patients

From the Department of Anesthesia and Perioperative Care, University of California, San Francisco and Department of Cardiovascular Anesthesia, Kaiser Permanente Medical Center, San Francisco, California.

Address correspondence to Jacqueline M. Leung, MD, MPH, University of California, San Francisco, Mount Zion Medical Center, Department of Anesthesia and Perioperative Care, 1600 Divisadero Street, C-355, San Francisco, CA 94143–1605. Address email to jmleung{at}itsa.ucsf.edu

	Abstract

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Preoperative assessment of heart function has typically focused on evaluating left ventricular ejection fraction (LVEF). Recent evidence suggests that diastolic heart failure is common and may cause substantial morbidity and mortality. We designed this study to examine the prevalence and potential clinical correlates of diastolic filling abnormalities as measured by echocardiography in geriatric surgical patients. Patients 65 yr of age undergoing coronary artery surgery without concomitant valvular surgery or those with one or more risk factors for cardiovascular disease undergoing noncardiac surgery were prospectively studied. Preoperative precordial echocardiography was performed for patients undergoing noncardiac surgery, and intraoperative transesophageal echocardiography was performed for those undergoing cardiac surgery. LVEF and diastolic filling properties including E/A ratio and deceleration time were measured. Overall, 251 patients were enrolled. The mean age was 72 ± 7 yr. Multiple linear regression analyses showed that patients with a history of myocardial infarction P = 0.021), angina pectoris (ß = -6.09, 95% CI: -9.66, -2.52; P = 0.01), and valvular heart disease (ß = -5.05, 95% CI: -9.56, -0.55; P = 0.028) had lower LVEF than those without such conditions. Of the patients with normal LVEF, 61.5% had diastolic filling abnormalities. Diastolic filling indices including E/A ratio (ß = -1.11, 95% CI -6.02, 3.78; P = 0.65) and deceleration times (ß = -3.42, 95% CI -31.28, 24.45; P = 0.81) contributed no additional predictive value for LVEF. No clinical predictors could be identified to predict diastolic filling abnormalities. For patients undergoing noncardiac surgery, analysis of variance demonstrates that the clinical assessment of LVEF using history and physical examination data was able to grossly discriminate the different levels of LVEF as compared with echocardiography (P = 0.0004). However, under-estimation of LVEF occurred more frequently than over-estimation. Although physicians’ clinical assessment of systolic ejection fraction was generally accurate, geriatric patients with normal LVEF often had isolated diastolic filling abnormalities that could not be predicted by clinical factors. These results suggest that evaluation of LV systolic function alone is not discriminatory in comprehensively characterizing LV function in geriatric surgical patients.

IMPLICATIONS: Although physicians’ clinical assessment of systolic ejection fraction was generally accurate, geriatric patients with normal left ventricular (LV) ejection fraction often had isolated diastolic filling abnormalities that could not be predicted by clinical factors. These results suggest that evaluation of LV systolic function alone is not discriminatory in comprehensively characterizing LV function in geriatric surgical patients.

	Introduction

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Congestive heart failure is one of the most common postoperative cardiac complications occurring in elderly surgical patients (1). We also demonstrated that a history of congestive heart failure was associated with adverse postoperative cardiac outcomes and in-hospital mortality in geriatric surgical patients (1). In nonsurgical patients, the mortality risk for patients with congestive heart failure has been reported to be as frequent as 50% at 2 yr after diagnosis (2). It is common belief that systolic function decreases with age, but in fact, in the absence of co-existent cardiovascular disease, resting systolic cardiac function is well preserved even at very advanced age (3). Despite the preservation of left ventricular (LV) systolic function, heart failure can also result from LV diastolic dysfunction that is frequently not emphasized in routine preoperative testing.

Clinical diagnosis of heart failure in older patients may be difficult because of the lack of typical symptoms and physical findings (4). In patients with a history of congestive heart failure, one-third may present with normal systolic function (5). The assessment of diastolic filling in these patients may be particularly important, as diastolic dysfunction may be an alternate etiologic cause for heart failure. During diastolic dysfunction, there is an impairment of the ventricle to accept blood or fill without an abnormal increase in atrial and ventricular filling pressure (6). Such abnormalities may affect only the early rapid filling phases, which are dependent on active ventricular relaxation, or throughout entire diastole including the later phase, which is associated with ventricular stiffness and distensibility (7). Disorders associated with diastolic function include systemic hypertension, coronary artery disease, cardiomyopathies, aortic stenosis, atrial fibrillation, diabetes, and chronic renal disease (4).

Although some population studies have reported on the general incidence of diastolic function in adult population, the specific prevalence of diastolic dysfunction in the geriatric surgical patients is unknown. Furthermore, because the diagnosis of diastolic heart failure is usually clinically based, determining the clinical correlates of diastolic dysfunction in this surgical cohort would be clinically important. Accordingly, the study aims of the present investigation were as follows: 1) to determine the prevalence and predictors of preoperative diastolic filling abnormalities as assessed by echocardiography in geriatric surgical patients awaiting surgery; and 2) to determine the accuracy of estimating preoperative LV ejection fraction (LVEF) using information derived from routine physical examination and history. We hypothesized that geriatric patients judged clinically and echocardiographically to have normal LVEF might have significant cardiac dysfunction, notably diastolic filling abnormalities.

	Methods

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The study was approved by the institutional committees on human research and conducted at one of the teaching hospitals of the University of California, San Francisco, and also at Kaiser Permanente Medical Center, San Francisco. Informed consent was obtained for all patients undergoing noncardiac surgery. For the cardiac surgical patients, this study was exempted from the requirement of obtaining informed consent because it involved the collection of existing documents, records, and diagnostic data. The inclusion criteria were surgical patients 65 yr of age presenting for either coronary artery surgery without concomitant valvular surgery or noncardiac surgery, with one or more risk factors for cardiovascular disease, such as a history of smoking, hypertension, diabetes mellitus, or hypercholesterolemia. These coexisting conditions were clinically determined, abstracted from patient’s medical records.

For patients undergoing noncardiac surgery, preoperative precordial echocardiography was performed, and for patients undergoing cardiac surgery, intraoperative transesophageal echocardiography was performed before the surgical procedure. All echocardiographic examinations were performed by an experienced and certified sonographer. Either the Acuson (Mountain View, CA) or Hewlett Packard (Andover, MA) echocardiographic systems were used. A complete cardiac examination was performed with particular attention to evaluating LV systolic function and diastolic filling abnormalities. The video images were recorded on VHS videocassette tapes.

Videotaped images were analyzed on a Freeland/Tomtec Cardiology Workstation, (Boulder, CO). For LVEF, three separate cardiac cycles were measured from the LV mid-papillary short axis view. The LV end-systole area (ESA) and end-diastole area (EDA) were traced for each of the three cardiac cycles, and an average value was calculated. Fractional area change was calculated as ((EDA - ESA)/EDA) x 100%. Interobserver variability was determined by a second investigator repeating the above procedures.

Diastolic filling properties were analyzed using Doppler echocardiography. Of the several Doppler indices used to measure diastolic dysfunction, the ratio of the peak early to the peak atrial mitral inflow velocities (E/A ratio) and the deceleration time of the peak early inflow (deceleration time) are the most widely used indices and are recommended in the latest guidelines for diagnosing diastolic dysfunction (8,9). Mitral inflow velocities were measured at end-expiration at the level of the four-chamber view, at the tips of the mitral leaflets using Pulsed Doppler, performed at end-expiration (10). The Doppler beam was aligned to produce the narrowest possible angle between the beam and the blood flow vector. Measurements were also repeated during Valsalva maneuver to unmask pseudonormalization of mitral inflow velocities (11). The peak velocity during early filling (E), late filling from atrial contraction (A), the E/A ratio, and the deceleration time from peak early filling extrapolated to the baseline were measured. Paired E/A complexes were traced to derive an average value.

Pulmonary venous flow velocity was recorded in the apical 4-chamber view from the right pulmonary vein by placing the sample volume 1–2 cm into the pulmonary vein proximal to its entrance into the left atrium (12). For transesophageal echocardiographic monitoring, the mid-esophageal 4-chamber view was used to image the left upper pulmonary vein. The peak systolic and diastolic velocities were recorded, and the peak systolic/diastolic velocity ratio was computed. In addition, the duration of the atrial systolic reversal wave was measured and the difference between the durations of the pulmonary venous atrial reversal and transmitral A waves (AR-A) was calculated (13).

Diastolic filling was classified as normal, mild dysfunction with impaired relaxation but normal LV filling pressures at rest, mild to moderate dysfunction with impaired relaxation and likely increased LV end-diastolic pressure, moderate dysfunction with increased LV filling pressures (pseudonormal pattern), and severe dysfunction with high LV filling pressures (restrictive) (Table 1) (14).

All statistical analyses were performed using commercially available software (Stata 5.0; Stata, College Station, TX). The mean LVEF between subgroups of patients were compared with unpaired Student’s t-test or analysis of variance. Nonparametric data were assessed by the Kruskal-Wallis test. Analyses of association between LVEF and each of the Doppler indices of diastolic dysfunction, and the relationship between each potential clinical factor and LVEF and diastolic filling abnormalities were conducted using multivariable linear regression modeling. A P value <0.05 was considered statistically significant in the final model.

The relationship between clinical assessment and echocardiographic measurement of LVEF was evaluated using one-way analysis of variance and the strength of the association was measured using an F-test.

	Results

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Overall, 251 patients were enrolled. The mean age was 72 ± 7 yr. Thirty-eight percent were women and 62% were men. The mean LVEF was 54.3 ± 13.1% (range, 16.5%–81.3%). Of the patients included in the study, 33.2% had LVEF <50%. The general demographics of the patients are shown in Table 2. A history of hypertension, angina pectoris, and tobacco use were the most common coexisting conditions. Twelve percent of the patients had a history of congestive heart failure. Patients who had a history of myocardial infarction, angina pectoris, and valvular heart disease had significantly lower LVEF than those without such conditions (Table 3). None of the other clinical conditions including age showed significant associations with LVEF.

View larger version (13K): [in this window] [in a new window]   Figure 1. Left ventricular function as measured by ejection fraction (LVEF) is plotted against diastolic filling as measured by E/A. The data are scattered with no association between the two variables of interest.

View larger version (13K): [in this window] [in a new window]   Figure 2. Left ventricular function as measured by ejection fraction (LVEF) is plotted against diastolic filling as measured by deceleration times. The data are scattered with no association between the two variables of interest.

To evaluate the accuracy of clinical assessment of LVEF in patients undergoing noncardiac surgery, 37 of 117 patients were excluded from the analysis because of previous reports of LVEF existing in the chart (n = 34) or poor quality echocardiograms (n = 3). For patients included in this survey, the mean LVEF was 50% ± 12% (range 16.5%–79%). Overall, 21.9% of patients had LVEF <50%. Analysis of variance demonstrates that the 3 classes of LVEF as determined by clinical assessment were distinctly different (P = 0.0004). For the patients deemed to have severely depressed LV function, the actual mean LVEF measured by echocardiography was 27%; for those having mild to moderate depressed LV function, the actual mean LVEF was 57%; and for those having normal LV function, the actual mean LVEF was 64%. Of the overall incorrect responses, 33 of 37 (89%) were under-estimations of ejection fraction, and 4 of 37 (11%) were over-estimations. Therefore in this study, patients with normal LVEF were more frequently labeled as abnormal.

Of the clinical information used by anesthesiologists, medical history was used most frequently to estimate LVEF (91.3%), followed by physical examination (70%) or preoperative cardiac data (other than echocardiography) (65%). Considering all the preoperative cardiac tests, evidence of prior myocardial infarction on electrocardiogram (ECG) was most frequently used (58.9%) to estimate LVEF. Other cardiac tests used to estimate LVEF included pharmacologic stress tests and coronary angiogram.

	Discussion

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This is one of the first studies to evaluate the prevalence and potential predictors of LV diastolic filling abnormalities in a group of elderly surgical patients. We found that more than half of the patients had evidence of isolated diastolic filling abnormalities. A study of consecutive medical patients referred to an echocardiographic laboratory for evaluation found that 45% of patients with normal LVEF had abnormal diastolic function (14). A recent cross-sectional survey of more than 2000 randomly selected residents aged 45 years of age from Olmsted County, MN, found that 28.1% of the patients with an LVEF >50% had diastolic dysfunction measured by Doppler echocardiography (15). The difference in the prevalence of diastolic dysfunction in these studies versus ours is probably not solely a result of the definitions of diastolic dysfunction. Although there are some minor differences in defining the upper limits of normal versus mild diastolic dysfunction in these studies, the likely reasons for the more frequent rate of diastolic dysfunction in our study are the prevalence of coexisting cardiovascular disease and age of the study cohort. The patients in our study were preselected for being at high risk for coronary artery disease or having documented coronary artery disease. As reported previously, those with cardiovascular disease have been demonstrated to have an increased prevalence of diastolic dysfunction (16). Furthermore, the patients in our study were substantially older (mean age of 72 years) versus those reported in these previous studies (mean age 62 years).

Age has been shown to have a significant effect on mitral indices of diastolic dysfunction (14,16). Specifically, peak early mitral inflow velocity and the E/A ratio decline with increasing age, and early inflow deceleration time and peak atrial inflow velocity show a significant increase with advancing age (16). In a population study, Redfield et al. (15) demonstrated that the prevalence of diastolic dysfunction was substantially more frequent in subjects aged 65 years versus those aged 45–64 years (53.9% versus 12.8%, respectively). In healthy older humans, aging affects the vasculature through increase in the wall thickness, the diameter, and the vascular stiffness of the aorta and large arteries. As a result, systolic and mean arterial blood pressures increase with widening of the pulse pressure (17). In subjects with hypertension, these vascular changes are manifested by impairment of the early diastolic LV relaxation and a compensatory increase in atrial filling (18). Other age-related changes include increases in the LV wall thickness secondary to enlargement of cardiac myocytes (17). Myocardial compliance is decreased, with reduction in the early diastolic filling rate and compensatory augmentation of the contribution of atrial contraction to late LV filling.

During preoperative testing when LVEF has been quantitatively measured, anesthesiologists are often assured when the record indicates a normal LVEF. However, our study demonstrates that despite the relatively accurate preoperative assessment of LVEF using clinical information, isolated diastolic filling abnormalities are prevalent. These results suggest that the preoperative evaluation of LV function in geriatric surgical patients should be reappraised. Specifically, the isolated focus on normal LVEF may not be sufficient to describe the overall heart function of patients. Ventricular diastolic dysfunction, with prolonged relaxation, should be considered in any elderly patient with a history of decreased exercise tolerance. In fact, a study of general medical patients reported that a majority of patients who were presumed to have diastolic heart failure were mislabeled and their symptoms and signs attributed to other medical conditions, such as obesity or pulmonary disease (19). Furthermore, the differentiation between systolic and diastolic heart failure is difficult if relying simply on history, physical examination, ECG, or chest radiograph alone because markers from these examinations occur with the same relative frequency in both systolic and diastolic heart failure (20,21). An important finding in the present study is that no clinical marker can be identified to predict the occurrence of diastolic filling abnormalities.

What are the clinical implications for diastolic filling abnormalities detected preoperatively? If we consider echocardiographically measured diastolic filling abnormalities as possible markers of diastolic dysfunction, then diastolic heart failure (defined as preserved LVEF and abnormal diastolic function) may be prevalent in elderly patients awaiting major surgery and should be further evaluated. In a population study, diastolic dysfunction has been associated with marked increases in all-cause mortality during long-term follow-up after adjusting for age, sex, and LVEF (15). This finding has been similarly demonstrated in other population studies, where the prognosis of patients with diastolic heart failure is worse than that for age-matched controls (22–24). In certain cardiac conditions, diastolic abnormalities may precede systolic dysfunction (25,26), and impaired diastolic function is considered to have an important role in the production of symptoms of congestive heart failure. However, similar outcomes study is lacking in surgical patients. It would be important to determine if patients with diastolic filling abnormalities ultimately develop evidence of overt heart failure. Another consideration is that there is a wide range of normal values for the various Doppler echocardiographic variables of diastolic function reported for the elderly patients (14). It is difficult to distinguish between true relaxation abnormality and changes attributable to "normal" physiologic aging. However, even discounting the 48% mild diastolic filling abnormalities in our current study as possible "age-related changes," there remain 15.2% of patients with moderate-to-severe diastolic filling abnormalities. These observations suggest that diastolic function measurements in the elderly are complex, important, and worthy of further investigation. Future studies are needed to determine the prognostic importance of preoperative diastolic dysfunction and whether the assessment of diastolic heart function in patients with suspected heart failure may lead to more effective diagnosis and treatment of perioperative heart failure.

Our study is limited to evaluating only LV systolic and diastolic filling. We did not perform any outcome measurement to determine the association between diastolic filling abnormalities and postoperative cardiac morbidity. The prognostic significance of diastolic filling abnormalities in geriatric surgical patients with normal LV systolic function will need to be investigated by future studies. It remains to be determined whether elderly surgical patients with diastolic filling abnormalities have an increased risk of developing postoperative heart failure.

The measurement of the ratio between the peak early filling wave (E wave) and the atrial filling wave (A wave) from Doppler echocardiography is a useful screening tool for abnormal LV relaxation. However, it should be noted that most variables measuring diastolic function are dependent on the loading conditions, heart rate and age. Also, no single individual measurement can fully characterize LV diastolic function.

We measured LVEF using only one single plane of mid-papillary short axis view. In heterogeneously contracting ventricles (i.e., those with important wall motion abnormalities), ejection fraction measurement based on biplane volumes is recommended (27) because the apical bi-plane formula, by measuring LV wall motion over the entire length in two orthogonal planes, integrates regional wall motion abnormalities and yields a more accurate assessment of global LVEF.

For patients undergoing noncardiac surgery, we performed transthoracic echocardiography while they were awake and breathing spontaneously, and for those undergoing cardiac surgery, transesophageal echocardiography was performed while the patients were anesthetized and receiving positive pressure ventilation. The latter conditions may have resulted in changes in loading condition, thereby affecting diastolic function measurements. However, the filling pressures as measured by pulmonary capillary wedge pressure in the surgical patients were not significantly different before and after anesthetic induction, suggesting that anesthesia and sedation in this study had minimal effects on our measurement of diastolic filling properties.

In conclusion, our study demonstrates that elderly patients with normal LVEF frequently have diastolic filling abnormalities. Future studies will be necessary to determine the prognostic importance of diastolic dysfunction on perioperative cardiac morbidities.

	Acknowledgments

 
Supported, in part, by the National Institutes of Health Grant #1K24 AG00948–01A2.

	References

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999