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Departments of *Medicine and Cardiology, CHUM, Notre-Dame Hospital; and Department of Anesthesia, Montreal Heart Institute Montreal, Quebec, Canada
Address correspondence and reprint requests to Dr. Denault, Department of Anesthesia, Montreal Heart Institute, 5000 Belanger St. East, Montreal, Quebec H1T 1C8, Canada. Address e-mail to denault{at}videotron.ca
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Abstract |
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Implications: Abnormal diastolic filling patterns are frequently observed during cardiac surgery. The data support routine evaluation of diastolic function during echocardiographic cardiac assessment of patients undergoing cardiac surgery.
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Introduction |
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Myocardial function can be analyzed according to systole and diastole. Historically, systolic function has drawn more attention than its counterpart. Systolic dysfunction is a prognostic factor in heart failure (4), for inotropic support after CPB (2,5), and for mortality after cardiac surgical procedure (6–8). The natural evolution of systolic function after a cardiac surgical procedure and its determinants are well described (9). Diastolic function is receiving more attention since echocardiographic measurements were developed and became widely available (10–13). Diastolic dysfunction (DD) is thought to be the earliest marker of myocardial ischemia (14–16), to have a prognostic significance in heart failure (4,10,17–19), and to reflect accurately the clinical functional status of patients with heart failure (20,21). One study failed to demonstrate that DD was correlated with a worse postoperative outcome (22). However, the patients in that study had only a relaxation deficit, which is considered the less severe form of DD. Nonetheless, the authors found that the incidence of DD in the coronary artery bypass grafting (CABG) surgical population was 77% (22).
In this study, we hypothesize that DD can be a predictor for the need of inotropic support to successfully separate from CPB. This observation would have a clinical impact because treatment of DD could then be envisaged, and inotropic and lusitropic therapy could be tailored to better fit the heart’s physiology and facilitate weaning from CPB (1,23–28).
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Methods |
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Relevant medical history included age, sex, height, weight, medication, diabetes, hypertension, prior myocardial infarction, unstable angina, electrocardiographic evidence of ischemia on the day of the surgery, type of surgery, and number of vessels grafted.
The anesthetic management included use of a pulmonary artery catheter, electrocardiogram, pulse oximetry, capnography, and a radial artery catheter. Sixty-one patients received a combination of fentanyl or sufentanil with midazolam and isoflurane as anesthetics. The remaining five patients were managed with halothane and a spinal anesthetic with or without infusion of propofol. After the induction, a multiplane transesophageal echography (TEE) probe (Sonos 1500, Omniplane 3.5–5.0-MHz ultrasonic transducer probe; Hewlett-Packard, Andover, MA) was introduced to obtain the sequence of cardiac images before pericardiotomy during a period of hemodynamic stability after the anesthetic induction. Postcapillary wedge pressure, central venous pressure, systemic blood pressure, cardiac index, and heart rate were recorded at the time of image acquisition.
TEE evaluations were performed by an anesthesiologist certified in perioperative TEE who was not in charge of the patient. The anesthesiologist in charge was blinded to the diastolic evaluation. The examinations were later reviewed separately by an anesthesiologist and a cardiologist who specialized in TEE. The two examiners were blinded from clinical data except the age of the patient, which is necessary for correct interpretation of diastolic variables. If there was a disagreement between the two reviewers as to whether DD was present, the examination was reviewed and, if necessary, a third echographist analyzed the data until a consensus was reached. Our experience in the use of TEE and our interobserver and intraobserver variability has been previously published for the evaluation of systolic and diastolic function (29,30).
Systolic function was evaluated by the fractional area change (FAC) and the Regional Wall Motion Score Index (RWMSI). FAC was defined by the difference between the end diastolic area and the end systolic area divided by the end diastolic area at the transgastric midpapillary view. The RWMSI was evaluated on six segments at the transgastric midpapillary view, as described by the American Society of Echocardiography (31). An abnormal RWMSI was defined as being more than 1.5.
Left ventricular diastolic function was reported according to the "Canadian Consensus Recommendations for the Measurement and Reporting of Diastolic Dysfunction by Echocardiography" (10). Mitral inflow velocities were measured at the tip of the mitral leaflets on three consecutive heartbeats at the end of expiration. The variables recorded were the following: peak velocity of early diastolic filling wave (E) and late diastolic filling wave (A), the ratio of these two velocities (E/A), and deceleration time (dt). Peak systolic (S), diastolic (D), and atrial reversal (Ar) pulmonary vein flow velocities were measured in the left and the right upper pulmonary veins. The DD patterns were classified into three groups with the following general criteria: impaired relaxation (E/A < 1.0, dt > 240 ms, and S > D), pseudonormal (E/A > 1.0–1.5, dt 160–200 ms, and S < D, with Ar > 35 cm/s), and restrictive (E/A > 1.5, dt < 160 ms, S < D, and Ar > 35 cm/s). The DD patterns were correlated with the age of patient by using Table 1 of the Canadian Consensus (10). Patients were excluded if they had cardiac surgery without CPB, heart rate more than 110 bpm, or persistent arrhythmia, or if they required a pacemaker.
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Difficult separation from cardiopulmonary bypass (DSB) was defined as a systolic arterial pressure <80 mm Hg and diastolic pulmonary artery pressure >15 mm Hg during progressive separation from CPB without inotropic or mechanical support of cardiac function (27) or hemodynamic instability resulting in the reintroduction of extracorporeal circulation or the insertion of an intraaortic balloon pump (IABP). Patients with successful weaning from CPB but requiring a significant amount of vasopressors (norepinephrine >4 µg/min or epinephrine >2 µg/min) or inotropic drugs (dobutamine >2 µg · kg-1 · min-1 or the use of amrinone and milrinone) during the first 12 h after surgery, IABP, or both were included in the group with DSB. In patients with difficult weaning, peripheral arterial pressure measurement was confirmed with aortic pressure measurement. In the ICU, the postoperative vasoactive management of the patients was done by the cardiac surgeon, who was blinded as to the presence or absence of prebypass DD.
Preoperative characteristics between patients with DD and normal diastolic function were analyzed with the 
2 test and Fisher’s exact test if the variables were noncontinuous and with the analysis of variance method if they were continuous. P < 0.05 was considered significant. The demographic, echocardiographic, and hemodynamic variables were entered in a logistic regression analysis to determine which variables were independent predictors of a difficult separation from CPB and to determine the need for postoperative vasoactive support. Univariate analysis was used for preliminary selection (
level of 0.25) of factors with P < 0.1 to be included in a stepwise hierarchical regression. The final model included all factors significant at the 0.05 level. Age, sex, weight, and height were included in the model to attenuate potential sampling biases. P < 0.05 was considered significant. Results are expressed as mean ± SD.
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Results |
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Preoperative, intraoperative, and postoperative characteristics from patients with and without DD are listed in Table 1. DD was present in 20 patients (30%). Patients with DD had lower weight (P = 0.04), less frequent CABG alone (P = 0.0004), more myocardial infarction before surgery (P = 0.02), increased RWMSI (P = 0.0002), and larger left ventricle (P = 0.03). The FAC was not statistically different in the two groups. In this population, 44% of patients with DD had normal FAC, and 40% had normal RWMSI. Total CPB time (P = 0.004) and ischemic time (P = 0.007) were longer in the DD group. Patients with DD required inotropic support at the end of surgery (P = 0.006) and up to 12 h after surgery (P = 0.003). The proportion of impaired relaxation, pseudonormal pattern, and restrictive pattern of DD were 50%, 40%, and 10%, respectively. The pseudonormal and restrictive patterns were more common in patients requiring inotropic support than relaxation abnormalities. DD was associated with longer surgical ICU (P = 0.05) and total hospital stay (P = 0.08) before discharge, but this did not reach statistical significance.
Two patients had prophylactic IABP placement before surgery, and one of them also had inotropic drug support initiated before the procedure. For this latter patient, inotropic requirements significantly increased after CPB, and thus this patient was considered to have a difficult weaning from CPB. One patient died immediately after surgery and another one, 3 days later. Both of them had DD. The one who died immediately after surgery had a restrictive pattern.
By using univariate logistic regression, sex, age, DD, RWMSI, ischemic time, and total CPB time were predictive of difficult weaning from CPB and inotropic requirements up to 12 h after surgery. Ventricular enlargement, FAC, and preoperative use of angiotensin converting enzyme inhibitors were not predictive ( Table 2). Multivariate logistic regression identified female sex, DD, and total CPB time as predictive of difficult weaning and inotropic requirements up to 12 h after surgery ( Table 3). The univariate and multivariate analysis remained significant, with the exclusion of patients undergoing valvular surgery.
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Discussion |
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As secondary findings, we observed a 30% incidence of DD in 66 consecutive patients undergoing elective cardiac surgery. Relaxation abnormality was the most common form of DD observed. Half of our patients had hypertension, and DD has been reported in as many as 90% of patients with hypertension (17). In addition, we observed that DD was present in patients with a history of previous myocardial infarction, increased RWMSI, and left ventricular dilation. Our observations are consistent with the known relationship between coronary artery disease and DD, in which relaxation is affected before contractility. Because relaxation of the myocytes in diastole is a process that is energy dependent and thus sensitive to impaired perfusion, this is most likely the explanation of why DD is an early marker of ischemia (14–16,33).
The most common predictors of DSB are older age, female sex, lesser ejection fraction, ventricular enlargement, ischemic time, and total CPB (2). We found female sex and duration of CPB to be predictors of DSB; however, age was not. Interestingly, the logistic regression analysis did not include the FAC categories and left ventricular (LV) dilation as predictors of DSB, despite decreased FAC, increased RWMSI, and LV dilation in the DD group. This could be related to the small size of our sample. In this study, DD is not necessarily always associated with decreased FAC or ventricular enlargement. In fact, 44% of patients with DD had normal FAC, and 40% had normal RWMSI. Moreover, dilation was not observed solely in patients with DD. This illustrates that LV enlargement and systolic function assessed by FAC are useful determinants of cardiac function but that DD may play an additional role in predicting difficult weaning from CPB. These observations also support the view that diastolic function may better correlate with cardiac functional status than FAC or ventricular enlargement alone. Indeed, the presence of DD becomes most useful when the traditional cardiac evaluation variables show no abnormalities, enabling us to identify higher risk patients who would otherwise have been classified as low risk.
Diastolic function is gaining popularity and recognition in the medical literature. It is now well established that diastolic function, just as systolic function, has clinical, therapeutic, and prognostic implications. Certain authors consider the ventricular filling more important than systolic function as a determinant of cardiac performance (11). The observation that DD identifies high-risk patients possibly resides, in part, in the effect of revascularization on the myocardium. Chronically ischemic or hibernating myocardium that is reperfused through new vascular grafts may markedly improve in function, whereas myocardium previously served by normal or partially, but not critically, reduced myocardial blood flow may suffer from a reperfusion injury, with subsequent decrease in myocardial function (9). Furthermore, if revascularization is incomplete and postoperative conditions lead to increased myocardial oxygen consumption, ischemic myocardium may suffer more from these deleterious conditions. DD, as we have seen earlier, may indicate more ischemic myocardium and thus greater extent of muscle susceptible to reperfusion injury or ischemic insult. Also, DD may dictate the need for increased filling pressure, which in turn can lead to subendocardial ischemia because the pressure gradient from the aorta to the myocytes, and thus blood flow, is reduced in this situation.
These observations may have potential clinical implications because the prophylactic drug administration can be used before separation from CPB (1,5), and the choice of these drugs could be influenced by the presence of DD. Phosphodiesterase inhibitors improve diastolic function and thus are classified as lusitropic through several mechanisms (23) and are used to facilitate separation from CPB (24–28). Most of the literature attributes this latter phenomenon to the increase in cardiac index, presumably through improvement of systolic function, but diastolic function may well play an important role in optimizing contractility (23). Phosphodiesterase inhibitors have the advantage of improving systolic and diastolic function without increasing oxygen consumption (5). It has been suggested that ß-blockers may also be valuable in ameliorating diastolic variables of the ventricle because reducing chronotropy offers a longer refilling period in patients with impaired relaxation.
This study has some limitations. First, because diastolic function has many determinants and some of these have been proven to influence the weaning process, we have to consider that DD may simply act as a marker without any prognostic implication in itself. However, our observations militate against this hypothesis because DD was found to be an independent predictor of difficult weaning from CPB in this study. Therefore, the detection of DD can provide additional information, as compared with previously used criteria.
Second, different patterns and reversibility of DD can vary in their ability to predict difficult weaning from CPB. In contrast to Oppizzi et al. (22), who reported only relaxation abnormalities in their surgical population, half of our DD were classified as having pseudonormal or restrictive abnormalities. They did not observe an association between DD and adverse ICU prognosis. The different pattern of DD can be viewed as a continuum of severity that can change over time, with the restrictive form being the most severe and the relaxation defect the mildest. In our study, patients requiring inotropic support more often had the pseudonormal and restrictive pattern. A difference in population with a more severe form of DD could explain why we observed a relationship with DD and DSB. The reversibility or improvement of DD was not evaluated, and it is possible that the presence of DD is variable during the process of cardiac surgery and that further information can be obtained from a more continuous intraoperative and postoperative evaluation. The absence of such reversibility could represent a more deleterious factor than the presence of DD itself, as it could identify more impaired hearts. An early study by Miller et al. (34) showed that DD was improved after CABG, but this amelioration was predominant in patients with ischemic myocardium and not in those with transmural infarction. This is consistent with our observations that more patients with DD have a previous myocardial infarct. Oppizzi et al. documented that DD persisted during the ICU stay, but after three months from CABG, it normalized in 85% of their patients. This observation was also demonstrated as early as one week after CABG in a study not designed to evaluate morbidity or mortality (35). We demonstrated in our study that the presence of DD influences the weaning process from CPB, but it is unknown whether it has prognostic implications for other postoperative complications, such as myocardial ischemia, renal dysfunction, neurological impairment, or respiratory insufficiency. Because pseudonormal and restrictive diastolic patterns are associated with increased LV filling pressures and less favorable operating pressure-volume curves, we would expect a more difficult weaning from CPB in these patients. This was consistent with our observations. However, our number of patients was not large enough to evaluate the impact of the type of baseline DD pattern on the subsequent clinical course. However, the presence of DD seems to correlate with a longer ICU and hospital stay after surgery.
Third, we included patients with valvular replacements, and DD is frequent in this group of patients. DD was relatively more frequent in the non-CABG group. Because of their small number, we repeated the logistic regression analysis, excluding these patients, and observed that DD remained associated with DSB and vasoactive requirements in the ICU. As another limitation, ejection fraction and RWMSI are dependent on preload and afterload conditions, and we did not evaluate ventricular systolic function with load-independent indices1(36). It is also unknown how much the evaluation of diastolic function is altered by changes in preload and afterload that occur after the induction of anesthesia and by the type of anesthetic. We performed our evaluation of diastolic function during a period of hemodynamic stability before cardiotomy but did not control for the type of the induction and anesthetic.
Finally, the evaluation of diastolic function has since made considerable progress since the Canadian Consensus on Diastolic Dysfunction. The importance of the technical aspects of Doppler velocity recordings on the reliability of data has been well illustrated (37). Newer technologies to evaluate LV diastolic function, such as color M-mode Doppler, tissue Doppler echocardiography of the mitral valve annulus, and the LV wall, as well as regional assessment of diastolic function by myocardial strain rate imaging, may help us better discern the contribution of relaxation and compliance abnormalities, the level of filling pressures, and subsequently the impact of changing loading conditions in the perioperative period. For instance, there have been recent studies using three-dimensional magnetic resonance imaging that demonstrate regional variation in the velocity recorded in the mitral inflow in such a way that the maximum velocity recorded in two planes should be recorded (38). This could alter the interpretation of the E/A ratio when used alone to evaluate DD. The pulmonary venous flow, conversely, is extremely sensitive to loading changes (39,40). The extent that a single diastolic function evaluation done after the induction of anesthesia reflects the overall diastolic reserve or the exact positioning of the patient on the diastolic pressure-volume curve is unknown. Dynamic testing of diastolic function may appear as a more attractive test to evaluate this aspect.
In conclusion, abnormal diastolic filling patterns are frequently observed during cardiac surgery. They are more common in patients with altered LV function. DD present before CPB was associated with an increased risk of DSB and vasoactive support in the ICU. The data support the view that evaluation of diastolic function should be routinely part of the echocardiographic assessment of patients undergoing cardiac surgery. Further studies using the newer tools for diastolic function evaluation in a larger number of patients and longer follow-up will be required to better assess the natural evolution and the reversibility of DD on patient outcome.
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Footnotes |
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