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Use of Intraventricular Dispersion of the Peak Diastolic Flow Velocity as a Marker of Left Ventricular Diastolic Dysfunction in Patients with Atrial Fibrillation
Use of Intraventricular Dispersion of the Peak Diastolic Flow Velocity as a Marker of Left Ventricular Diastolic Dysfunction in Patients with Atrial Fibrillation Omer Kozan, MD, Cem Nazli, MD, Ozan Kinay, MD, Oktay Ergene, MD, Ece Isguzar, MD, Batuhan Tamci, MD, B. Yildirim Seyithanoglu, MD, Umit Tekin, MD, Ulku Ergene, MD, Ahmet Tastan, MD, and Vehip Keskin, MD, Izmir, Turkey
The aim of this study was to evaluate the use of intraventricular dispersion of the peak diastolic flow velocity as a marker of left ventricular diastolic dysfunction in patients with atrial fibrillation. Regional diastolic flow velocity patterns at 1, 2, and 3 cm away from the mitral tip toward the apex were simultaneously recorded with the mitral flow velocity pattern by using pulsed Doppler echocardiography in 24 patients with atrial fibrillation before electrical or medical cardioversion. Echocardiographic examination was repeated after 10 to 30 days (ie, at the time of recovery of left atrial mechanical functions) after cardioversion of atrial fibrillation in all patients. Thirteen patients were found to have diastolic dysfunction; the remaining 11 patients with a normal E/A ratio constituted the control group. Afterward, the data recorded before the cardioversion were analyzed for each patient. In
Left ventricular (LV) diastolic function can be assessed noninvasively by analysis of the pulsed Doppler mitral flow velocity pattern. In patients with sinus rhythm, simple Doppler indexes such as the ratio of mitral peak early diastolic flow velocity (E) to mitral peak flow velocity at atrial contraction (A) is usually sufficient for the diagnosis of LV diastolic dysfunction.1-9 This ratio, however, is not obtainable in patients with atrial fibrillation (AF) because of the lack of a synchronized atrial contraction. Therefore investigators tried to discover other parameters that could be used as a marker of diastolic dysfunction in patients with AF. In patients with sinus rhythm, it has been demonFrom the Departments of Cardiology and Emergency Medicine, Dokuz Eylul University Hospital, Inciralti, Izmir, Turkey. Reprint requests: Cem Nazli, MD, Mustafa Bey Cad No 12/6, Alsancak, 35220, Izmir, Turkey. Copyright © 1998 by the American Society of Echocardiography. 0894-7317/98 $5.00 + 0 27/1/93439
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subjects with normal diastolic function, the peak diastolic flow velocity (PDFV) at the mitral tips also was maintained at the positions 1 to 3 cm away from the tip in the left ventricular cavity (PDFV at the mitral tips: 0.84 m/s, PDFV at 3 cm: 0.85 m/s; P = .34). In contrast, the regional PDFV progressively decreased toward the apex in patients with diastolic dysfunction (PDFV at the mitral tips: 0.82 m/s, PDFV at 3 cm: 0.63 m/s; P = .0004). Only 77% of the initial velocity was maintained at 3 cm away from the mitral tips in patients with diastolic dysfunction, whereas almost 100% of the initial velocity was preserved in patients with normal diastolic function (P < .001). These findings suggest that the assessment of the intraventricular decrease in mitral PDFV may be used as a reliable marker of diastolic dysfunction in patients with atrial fibrillation. (J Am Soc Echocardiogr 1998;11:1036-43.)
strated that the regional peak diastolic flow velocity (PDFV) progressively decreases toward the apex in patients with diastolic dysfunction, whereas it is maintained throughout the LV cavity in patients with normal diastolic function.10 It has been suggested, but not yet proven, that this finding also can be used to assess LV dysfunction in patients with AF. This study was designed to elucidate whether the intraventricular dispersion of early diastolic filling velocity can be used as a reliable marker of diastolic dysfunction in patients with AF.
METHODS Fifty-two consecutive patients who were considered for conversion of AF to sinus rhythm in the Cardiology Department of Dokuz Eylul University Hospital from November 1996 to June 1997 were evaluated both clinically and echocardiographically before cardioversion.
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Exclusion criteria included a history or echocardiographic evidence of coronary artery disease (angina pectoris, prior myocardial infarction, LV wall motion abnormalities), valvular heart disease (mitral stenosis, aortic stenosis, moderate or severe aortic or mitral regurgitation), congestive heart failure (New York Heart Association functional class greater than 2 or signs of heart failure at physical examination, LV dilatation, ejection fraction < 50%), restrictive cardiomyopathy, idiopathic dilated cardiomyopathy, and pericardial disease (constrictive pericarditis, pericardial effusion). Six patients with coronary artery disease, 3 patients with mitral stenosis, 1 patient with aortic stenosis, 4 patients with moderate or severe aortic regurgitation, 6 patients with moderate or severe mitral regurgitation, 3 patients with congestive heart failure, 1 patient with idiopathic dilated cardiomyopathy, and 1 patient with pericardial effusion were excluded from the study. The study population consisted of 27 patients (15 women, 12 men; mean age 59.5 years) with nonvalvular atrial fibrillation who were converted to sinus rhythm either medically or by electrical cardioversion. Hypertension was present in 18 patients and LV hypertrophy was demonstrated in 5 patients.Twelve patients had minimal mitral regurgitation and 3 patients had minimal aortic regurgitation. Mitral valve prolapse was present in 3 patients and mitral annular calcification was detected in 4 patients. No other cardiovascular disease was observed in the whole study group. All patients gave informed consent for participation. Elective cardioversion of AF was accomplished pharmacologically in 13 patients with propafenone (600 mg, single oral dose) and with direct-current cardioversion (mean 1.9 shocks, mean 225 ± 85 J for success) in 14 patients, all of whom initially had no success with oral propafenone. The patients received no other antiarrhythmic medication for pharmacologic cardioversion. The duration of atrial fibrillation was determined either clinically by an abrupt, well-defined, onset of palpitations with subsequent electrocardiographic evidence of AF or only by electrocardiographic documentation during hospitalization.The duration of AF was unknown in 14 patients. The estimated duration of AF was less than 6 weeks in all patients with known duration of AF. Patients with an AF of more than 48 hours (4 patients) or with unknown duration of AF (14 patients) were examined with transesophageal echocardiography before electrical or medical cardioversion. None of the patients was found to have thrombus in the left atrium or left atrial appendage. All of these patients received anticoagulation therapy for 1 month after cardioversion. After successful cardioversion (either medical or electrical), all patients were discharged and received oral amiodarone therapy for the maintenance of the sinus rhythm. Atrial fibrillation relapsed in 3 patients, however, (all of whom had unknown duration of AF, and 1 patient had
Kozan et al 1037
Figure 1 Method of analysis of peak diastolic flow velocities within left ventricular cavity from apical 4-chamber view. Ultrasound beam is aligned parallel to mitral diastolic color Doppler flow. LA, Left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.
hypertension) during the follow-up period and these patients were excluded from the study. None of the patients had cerebrovascular events or other clinically evident arterial embolism immediately after cardioversion or during the follow-up period. The first transthoracic Doppler echocardiographic examination (ECHO 1) was performed before cardioversion.The echocardiographic recordings were obtained with the patients in the left lateral decubitis position. A commercially available echocardiograph (Accuson 128, Acuson Corporation, Mountain View, Calif) with a 2.5-MHz probe was used to record pulsed Doppler diastolic flow velocity patterns. Initially, the diastolic flow velocity pattern at the mitral tip was recorded. The mitral flow velocity pattern was obtained in the standard apical 4-chamber view with a sample volume placed between the tips of the mitral leaflets. The recordings of the regional pulsed Doppler diastolic flow velocity patterns at 1, 2 and 3 cm from the mitral tip toward the apex were subsequently obtained with minimal delay.The depth of each sample was 2 mm. The ultrasound beam was aligned as parallel to the flow as possible with the guidance of color Doppler flow imaging (Figure 1). No angle correction was made in the calculation of velocity from the Doppler signals. All recordings were performed during brief apnea at end-expiration to avoid the effects of respiratory variation. The mitral and regional flow velocity patterns at 1, 2 and 3 cm from the mitral tip toward the apex were traced along the darkest portion of the velocities to obtain the peak early diastolic flow velocities. The ratio of regional PDFV to mitral PDFV was calculated by averaging the val-
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Table 1 Comparison of the baseline characteristics of the patients Diastolic dysfunction (n = 13)
Normal (n = 11)
P
Sex (N, %): Men 4 (30.7) 5 (45.5) .45 Women 9 (69.3) 6 (54.5) Age 60 ± 5.7 59 ± 7.1 .18 Heart Rate (beats/min): ECHO 1 86.5 ± 7.5 89.1 ± 9 .45 ECHO 2 72 ± 5.8 73.1 ± 6.8 .60 LV dimensions: End-diastolic diameter 5.1 ± 0.37 4.9 ± 0.38 .17 (cm) End-systolic diameter 2.9 ± 0.25 3.0 ± 0.19 .068 (cm) EF (%) 62.4 ± 5.1 61.8 ± 6.3 .79 HT (%) 11 (84) 6 (54.5) .18 LV hypertrophy (%) 5 (38) 0 (0) < .05 Duration of AF (days) 8.1 ± 5.8 7 ± 10.4 .80 (in patients with known duration of AF) Patients with unknown 7 (53) 4 (36) .39 duration of AF (%) Time between cardioversion 19.3 ± 11.9 15.3 ± 11.6 .41 and ECHO 2 (days) ECH0 1, Transthoracic Doppler echocardiographic examination before cardioversion; ECHO 2, transthoracic Doppler echocardiographic examination after cardioversion; EF, ejection fraction; HT, hypertension; LV, left ventricle.
ues of 10 consecutive cardiac cycles. The interobserver and intraobserver variabilities of the measurement of flow velocities were not calculated because these variabilities in the measurement of mitral peak early diastolic flow velocity have been shown previously to be negligible.11 Full recovery of left atrial mechanical functions has been shown to be achieved within 1 week in patients with brief (< 2 weeks) and moderate (2-6 weeks) duration of AF and within 1 month in patients with prolonged (> 6 weeks) AF.12 Therefore the second transthoracic Doppler echocardiographic examination (ECHO 2) of patients with known duration of AF was performed 1 week after cardioversion. On the other hand, the second Doppler echocardiographic study was obtained 1 month after cardioversion in patients with unknown duration of AF. Patients with unknown duration of AF actually comprise patients with both brief and prolonged duration of AF. All of these patients, however, were assumed to have a prolonged duration of AF and the second echocardiographic examination was performed at 30 days.Thus even if some patients had experienced a brief duration of AF, the full recovery of left atrial mechanical functions in these patients was probably achieved more securely at 30 days. In the ECHO 2 examination, the mitral flow velocity pattern was obtained in the standard apical 4-chamber view
with the sample volume placed at the mitral tips. Patients with an E/A ratio of less than 1 were assumed to have LV diastolic dysfunction. Twenty-two patients received digoxin for pharmacologic control of the ventricular rate of AF before cardioversion. Use of digoxin was stopped in all patients after they converted to sinus rhythm. Patients with hypertension (17 patients) were receiving angiotensin-converting enzyme (ACE) inhibitors (lisinopril, enalapril, or fosinopril) (9 patients), indapamide (3 patients), verapamil (1 patient), diltiazem (1 patient) and metoprolol (1 patient) both before cardioversion and during the ECHO 2 examination after cardioversion. Two patients with hypertension were not on any antihypertensive medication. Statistical Analysis Values are expressed as mean ± standard deviation.The statistical significance of the difference in the data among the groups was tested by using the chi-square test for the discrete variables and unpaired t test for continuous variables. A P value of less than .05 was considered to be statistically significant.
RESULTS Thirteen patients were found to have diastolic dysfunction, whereas 11 patients demonstrated normal diastolic flow velocity pattern in the ECHO 2 examination. No significant difference was noted between the 2 groups with regard to age, sex, ejection fraction, LV dimensions, heart rate, and hypertension, but patients with diastolic dysfunction had a higher rate of LV hypertrophy (Table 1). The duration of AF before cardioversion (in patients with known duration of AF) was similar for both groups (patients with diastolic dysfunction: 8.1 ± 5.87 days, patients with normal diastolic function: 7 ± 10.4 days; P = .80).The number of patients with unknown duration of AF was higher in the group with diastolic dysfunction than in the normal group, but the difference was not statistically significant (53% versus 36%, respectively; P = .39). No statistically significant difference was found between patients with abnormal and normal diastolic function with regard to time interval between cardioversion and the second echocardiogram (19.3 ± 11.9 days versus 15.3 ± 11.6 days, respectively; P = .41) (Table 1). In subjects with normal diastolic function, the PDFV at the level of mitral tips (E0) and regional peak diastolic flow velocities at 1 cm (E1), 2 cm (E2) and 3 cm (E3) away from the tips that were recorded in the Doppler examination before the cardioversion
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Figure 2 Intraventricular peak diastolic flow velocity profile of patients before cardioversion. E(0), Peak mitral diastolic flow velocity at the mitral tip; E(1), peak mitral diastolic flow velocity at 1 cm away from the mitral tip; E(2), peak mitral diastolic flow velocity at 2 cm away from the mitral tip; E(3), peak mitral diastolic flow velocity at 3 cm away from the mitral tip.
Table 2 Comparison of the peak diastolic flow velocity at mitral tips with the regional peak diastolic velocities in patients with and without diastolic dysfunction Diastolic dysfunction
E0 (m/s) E1 (m/s) P E0 (m/s) E2 (m/s) P E0 (m/s) E3 (m/s) P
0.82 ± 0.83 ± .37 0.82 ± 0.73 ± .004 0.82 ± 0.63 ± .0004
0.17 0.16 0.17 0.16 0.17 0.16
Table 3 The ratios of regional peak diastolic flow velocities to E0 in patients with and without diastolic dysfunction
Normal diastolic function
0.84 ± 0.89 ± .039 0.84 ± 0.87 ± .20 0.84 ± 0.85 ± .36
0.25 0.25 0.25 0.25 0.25 0.27
E0, Peak mitral diastolic flow velocity at mitral tip; E1, peak mitral diastolic flow velocity at 1 cm away from mitral tip; E2, peak mitral diastolic flow velocity at 2 cm away from mitral tip; E3, peak mitral diastolic flow velocity at 3 cm away from mitral tip.
were as follows: E0 = 0.84 ± 0.25 m/s, E1 = 0.89 ± 0.25 m/s, E2 = 0.87 ± 0.25 m/s, E3 = 0.85 ± 0.27 m/s. In other words, the E wave velocity was maintained even at positions 1 to 3 cm away from the tip into the LV cavity. On the other hand, the early diastolic flow velocity decreased progressively from the mitral tip to the apex in patients with diastolic dysfunction (E0 = 0.82 ± 0.17 m/s, E1 = 0.83 ± 0.16 m/s, E2 = 0.73 ± 0.16 m/s, E3 =0.63 ± 0.16 m/s) (Figure 2). In patients with normal diastolic function, the comparison of PDFV at the mitral tip with the regional peak diastolic velocities revealed a significant acceleration at 1 cm (P = .039) but no significant differences at 2 cm and 3 cm from the mitral tip toward apex (P = .20, P = .36, respectively). On the other hand, E0 was significantly higher than E2 and E3
E1/E0 E2/E0 E3/E0
Diastolic dysfunction (n = 13)
Normal diastolic function (n = 11)
P
1.01 ± 0.10 0.90 ± 0.11 0.77 ± 0.17
1.06 ± 0.10 1.05 ± 0.19 1.01 ± 0.11
.21 .03 < .001
E0, Peak mitral diastolic flow velocity at mitral tip; E1, peak mitral diastolic flow velocity at 1 cm away from mitral tip; E2, peak mitral diastolic flow velocity at 2 cm away from mitral tip; E3, peak mitral diastolic flow velocity at 3 cm away from mitral tip.
in patients with diastolic dysfunction (P = .004, P = .0004, respectively) . The statistical significance of the difference was greatest at 3 cm from the mitral tips toward the apex (Table 2). The intraventricular decrease in diastolic flow velocity was quantified with the ratios of regional peak early diastolic flow velocity at 1, 2, and 3 cm from the mitral tip toward the apex to the E0. A progressive decrease in the ratio of the regional PDFV to E0 was observed in patients with diastolic dysfunction. In contrast, the PDFV profile was preserved throughout the LV cavity in the patients without diastolic dysfunction (Figure 3).The ratios at 2 and 3 cm away from the mitral tip were significantly smaller in patients with diastolic dysfunction than in the subjects with normal diastolic function (P = .03, P < .001, respectively) (Table 3). Only 77% of the initial velocity was maintained at 3 cm away from the mitral tips in patients with diastolic dysfunction, whereas almost 100% of the initial velocity was preserved in patients with normal diastolic function (P < .001).
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Figure 3 Comparison of the ratio of regional peak diastolic flow velocity to E0 among subjects with normal LV diastolic function and patients with diastolic dysfunction.
DISCUSSION Left ventricular diastolic performance is mainly dependent on 2 discrete factors: relaxation and compliance. During diastole, the left ventricle must receive an adequate filling volume while maintaining low intracavitary pressures. To accomplish this, the ventricular myocardium relaxes during early diastole and the walls distend readily, allowing the chamber to receive a wide range of inflow volumes at low filling pressures. The stiffness of the LV chamber depends on the passive elastic properties of the myocardium, the thickness of the ventricular wall, the geometry of the chamber, the interaction between the 2 ventricles, and the intrapericardial pressure.13 To ensure optimal diastolic filling, the left atrium also contracts before ventricular activation. Doppler echocardiography can be used as a noninvasive, easily performed and reliable method for the evaluation of diastolic performance. In the presence of slower LV relaxation but with otherwise normal chamber stiffness and filling pressures, the isovolumic relaxation time increases in response to a slower rate of LV pressure decay.8,14,15 After mitral valve opening, the rate of pressure decline slows down even further, and because the left atrial pressure is low, the transmitral pressure gradient is diminished. This results in a reduced rate of LV filling, a decline in E velocity, and a prolongation of deceleration time. The reduction in early filling and consequently in early atrial emptying produced by delayed
LV relaxation causes the atrium to have a relatively higher volume before its contraction, which results in a more vigorous contraction, with increased velocity accounting for the accentuated A wave. In summary, the typical pattern of mitral inflow velocity associated with delayed LV relaxation consists of an E/A ratio of less than 1, an increase in the deceleration time, a prolonged isovolumic relaxation time, and a relative increase in the atrial filling fraction. On the other hand, these parameters are affected by various factors such as age, heart rate, loading conditions, systolic dysfunction, and valvular insufficiencies. In addition, the E/A ratio and atrial filling fraction cannot be obtained in patients with AF. All these facts have led investigators to seek other reliable parameters that can be used for the assessment of LV diastolic dysfunction in patients with AF. Regional micromanometric LV pressure measurements in animal models have demonstrated an early diastolic positive intraventricular pressure gradient from base to apex in normal hearts.16 Courtois et al17 have also shown that this positive pressure gradient is lost or reversed in the presence of LV dysfunction. Beppu et al18 demonstrated in an animal experiment that contrast medium injected into the left atrium reached the LV apex in one diastole in normal hearts and did not reach the apex after coronary ligation. Their data suggest that early diastolic flow velocity is rapidly decelerated in the presence of LV systolic and diastolic dysfunction.The positive intraventricular pressure gradient is considered to
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maintain or accelerate the velocity of the early diastolic flow toward the apex, so its loss will result in progressive deceleration of the velocity within the LV cavity. Investigators have proposed that the loss of the intraventricular pressure gradient due to LV dysfunction may result mainly from the impairment of LV diastolic function. Color Doppler studies supporting this hypothesis have demonstrated that the velocity of LV diastolic flow propagation measured with color M-mode Doppler echocardiography decreases progressively from mitral tip to apex in the presence of LV diastolic dysfunction.19-21 Yamamato et al10 have suggested that the assessment of the intraventricular diastolic flow velocity profile may provide useful information about the LV diastolic functions, considering that the intraventricular diastolic flow velocity profile is altered in the presence of LV diastolic dysfunction. These researchers have demonstrated that the early diastolic flow velocity decreases progressively from the mitral tip into the LV cavity in patients with diastolic dysfunction, whereas the E value was maintained even at 1 to 3 cm away from the tip in healthy subjects, all of whom were in sinus rhythm. Similarly, the E value was maintained in the LV cavity in patients with isolated AF, whereas a marked intraventricular decrease in the PDFV was observed in the patients with AF and hypertension or dilated cardiomyopathic conditions who were assumed to have diastolic dysfunction. On the other hand, these patients were not converted into sinus rhythm and reevaluated for the presence of classical Doppler indexes of LV diastolic dysfunction. Currently it is still unclear whether the intraventricular dispersion of the early diastolic filling can be used as a reliable marker of LV diastolic dysfunction in patients with AF. We have shown that patients with AF and progressive intraventricular decrease in diastolic flow velocity demonstrated a typical pattern of diastolic dysfunction in Doppler examination after conversion to sinus rhythm. In contrast, patients with AF and a preserved intraventricular diastolic flow velocity pattern revealed a normal pattern of mitral diastolic inflow. Therefore our results are in concordance with the data of the previous studies suggesting the use of intraventricular dispersion of diastolic flow velocity in the assessment of diastolic dysfunction in patients with AF. Thus far, this is the first study demonstrating that the diastolic dispersion can be used as a reliable indicator of diastolic dysfunction in patients with AF. Our results also indicate that the measurement of the decrease at 3 cm from the mitral tip is enough to detect LV diastolic dysfunction, con-
Kozan et al 1041
sidering that the decrease in PDFV is highest at this point. The mechanism of acceleration of diastolic flow at 1 cm from the mitral tips in patients with normal diastolic function is unclear. It may be caused by the greater suctioning effect of LV relaxation at this point, because the diastolic excursion of LV walls is highest at this region.22 The alignment of the ultrasound beam exactly parallel to the stream line is crucial for the accurate measurement of regional PDFV. Color Doppler imaging was used for appropriate alignment of the ultrasound beam, but some errors may still exist in the acquisition of Doppler data, especially in cases in which obtaining a clear apical 4-chamber view was difficult. Aortic regurgitant flow is considered to alter diastolic intraventricular flow dynamics. The intraventricular diastolic flow stream is not straight in patients with regional wall motion abnormalities, so the ultrasound beam cannot be oriented parallel to the stream at all positions within the LV cavity. Therefore, measurement of the intraventricular decrease in PDFV cannot be used to assess LV diastolic dysfunction in patients with moderate or severe aortic regurgitation and LV regional wall motion abnormalities. It has been proposed that LV systolic dysfunction and LV enlargement might also account for the intraventricular dispersion of diastolic flow velocity.10,23 Early diastolic events in the left ventricle generally are regulated by LV relaxation and elastic recoil, and because the LV size and systolic functions are important determinants of these factors, LV dilation and systolic dysfunction may be associated with the loss of the positive intraventricular pressure gradient. Because LV systolic functions and diameters were normal in all of our patients, the progressive intraventricular decrease in PDFV in these patients was most likely attributable to LV diastolic dysfunction. Mitral flow velocity pattern is known to be affected by LV diastolic function and by loading conditions.7,9,24-27 Abnormal loading conditions may lead to a normalized pattern and some patients with diastolic dysfunction may be falsely regarded as “normal” in Doppler echocardiography. Loading conditions also may affect the intraventricular pressure gradient and hence the intraventricular diastolic flow velocity profile. In this study, the intraventricular pressure gradient was not measured and the relation between the intraventricular decrease in PDFV and intraventricular pressure gradient has not been demonstrated. Such a relationship is still hypothetical and it should
1042 Kozan et al
be documented with future studies by the use of high-fidelity manometer-tipped catheters for intraventricular pressure gradient measurement in animal and human models. The most important limitation of our study is the small number of patients, because of the difficulties in finding such a select group of patients fulfilling the inclusion criteria. Therefore these findings should be confirmed with future studies that include a larger number of patients. Certain medications, particularly calcium channel blockers, can affect measurements of diastolic function and therefore interfere with the interpretation of Doppler indices of diastolic function. ACE inhibitors and indapamide might also have some beneficial effects on diastolic function, possibly by reducing the LV mass.28 On the other hand, these drugs might also reverse the intraventricular dispersion of the PDFV as well as the mitral diastolic indices (ie, E/A ratio) by improving diastolic functions. For example, a patient with a normalized E/A ratio caused by chronic usage of calcium channel blockers or ACE inhibitors might also have no intraventricular dispersion of PDFV before cardioversion.This issue should be clarified with further studies. The assumption that the A wave necessarily reflects LV compliance and therefore diastolic function may result in a methodologic limitation. It may also reflect the force of atrial contraction and these may affect the interpretation of the measurements taken during the second echocardiographic examination. Although current data suggest that full recovery of left atrial mechanical functions is achieved within 1 week in patients with brief and moderate duration of AF and within 1 month in patients with prolonged AF,12 a few exceptional cases may still have incomplete recovery of atrial mechanical functions at this period. The peak A velocity may increase later as the force of atrial contraction increases and thus alter the E/A ratio. Abnormalities of LV compliance may be better demonstrated with gated radionuclide angiography and micromanometer pressure recordings, which reflect LV lusitropy independent of left atrial mechanical functions.29,30 In conclusion, these findings suggest that a progressive intraventricular decrease in peak early diastolic flow velocity mainly reflects LV diastolic dysfunction. Further investigations are necessary to assess the contribution of other factors to intraventricular dispersion of early diastolic filling. Our findings suggest that the intraventricular dispersion of early diastolic filling may be used as a reliable mark-
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er of diastolic dysfunction in patients with AF, but this should be confirmed with further studies. REFERENCES 1. Masuyama T, Kodama K, Nakatani S, Kitabatake A, Kamada T. Effects of changes in coronary stenosis on left ventricular diastolic filling assessed with pulsed Doppler echocardiography. J Am Coll Cardiol 1988;11:744-51. 2. Stoddard MF, Pearson AC, Kern MJ, Ratcliff J, Mrosek DG, Labovitz AJ. Left ventricular diastolic function: comparison of pulsed Doppler echocardiographic and hemodynamic indexes in subjects with and without coronary artery disease. J Am Coll Cardiol 1989;13:327-36. 3. Maron BJ, Spirito P, Green KJ, Wesley YE, Bonow RO, Arje J. Non-invasive assessment of left ventricular diastolic function by pulsed Doppler echocardiography in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 1987;10: 733-42. 4. Takenaka K, Dabestain A, Gardin JM, et al. Pulsed Doppler echocardiographic study of left ventricular filling in dilated cardiomyopathy. Am J Cardiol 1986;58:143-7. 5. Phillips CA, Coplan NL, Krakoff LR, et al. Doppler echocardiographic analysis of left ventricular filling in treated hypertensive patients. J Am Coll Cardiol 1987;9:317-22. 6. Kitabatake A, Inoue M, Asao M, et al. Transmitral blood flow reflecting diastolic behavior of the left ventricle in health and disease: a study by pulsed Doppler technique. Jpn Circ J 1982;46:92-102. 7. Vanoverschelde JLJ, Raphael DA, Robert AR, Cosyns JR. Left ventricular filling in dilated cardiomyopathy: relation to functional class and hemodynamics. J Am Coll Cardiol 1990; 15:1288-95. 8. Appleton CP, Hatle LK, Popp RL. Relation of transmitral flow velocity patterns to left ventricular diastolic function: new insights from a combined hemodynamic and Doppler echocardiographic study. J Am Coll Cardiol 1988;12:426-40. 9. St Goar FG, Masuyama T, Alderman EL, Popp RL. Left ventricular diastolic dysfunction in end-stage dilated cardiomyopathy: simultaneous Doppler echocardiography and hemodynamic evaluation. J Am Soc Echocardiogr 1991;4:349-60. 10. Yamamato K, Masuyama T, Tanouchi J, et al. Intraventricular dispersion of early diastolic filling: A new marker of left ventricular diastolic dysfunction. Am Heart J 1995;129:291-9. 11. Yamamato K, Masuyama T, Tanouchi J, et al. Peak early diastolic filling velocity may decrease with preload augmentation: effect of concomitant increase in a rate of left atrial pressure drop in early diastole. J Am Soc Echocardiogr 1993;6: 245-54. 12. Manning WJ, Silverman DI, Katz SE, et al. Impaired left atrial mechanical function after cardioversion: relationship to the duration of atrial fibrillation. J Am Coll Cardiol 1994;23: 1535-40. 13. Quinones M. Doppler assessment of left ventricular diastolic function. In: Nanda NC, editor. Doppler echocardiography. 2nd edition. Philadelphia: Lea & Febiger; 1993. p. 197-215. 14. Nishimura RA, Abel MD, Hatle LK, et al. Assessment of diastolic dysfunction of the heart: Background and current applications of Doppler echocardiography. Part II. Clinical studies. Mayo Clin Proc 1989 64:181-204. 15. Chen W, Gibson D. Relation of isovolumic relaxation to left
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24. Yamamato K, Masuyama T, Tanouchi J, et al. Importance of left ventricular minimum pressure as a determinant of transmitral flow velocity pattern in the presence of left ventricular systolic dysfunction. J Am Coll Cardiol 1993;21:662-72. 25. Thomas JD, Choong CYP, Flachskampf FA, Weyman AE. Analysis of the early transmitral Doppler velocity curve: effect of primary physiologic changes and compensatory preload adjustment. J Am Coll Cardiol 1990;16:644-55. 26. Choong CY, Abascal VW, Thomas JD, Guerrero JL, McGlew S, Weyman AE. Combined influence of ventricular loading and relaxation on the transmitral flow velocity profile in dogs measured by Doppler echocardiography. Circulation 1988; 78:672-83. 27. Masuyama T, St Goar FG, Alderman EL, Popp RL. Effects of nitroprusside on transmitral flow velocity patterns in extreme heart failure: a combined hemodynamic and Doppler echocardiographic study of varying loading conditions. J Am Coll Cardiol 1990;16:1175-85. 28. Bonow RO, Udelson JE. Left ventricular diastolic dysfunction as a cause of congestive heart failure. Mechanisms and management. Ann Intern Med 1992;117:502-10. 29. Bonow RO, Bacharach SL, Green MV, et al. Impaired left ventricular diastolic filling in patients with coronary artery disease: assessment with radionuclide angiography. Circulation 1981;64:315-23. 30. Magorien DJ, Shaffer P, Bush CA, et al. Assessment of left ventricular pressure-volume relations using gated radionuclide angiography, echocardiography, and micromanometer pressure recordings. A new method for serial measurements of systolic and diastolic function in man. Circulation 1983; 67:844-53.
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The aim of this study was to evaluate the use of intraventricular dispersion of the peak diastolic flow velocity as a marker of left ventricular diastolic dysfunction in patients with atrial fibrillation. Regional diastolic flow velocity patterns at 1, 2, and 3 cm away from the mitral tip toward the apex were simultaneously recorded with the mitral flow velocity pattern by using pulsed Doppler echocardiography in 24 patients with atrial fibrillation before electrical or medical cardioversion. Echocardiographic examination was repeated after 10 to 30 days (ie, at the time of recovery of left atrial mechanical functions) after cardioversion of atrial fibrillation in all patients. Thirteen patients were found to have diastolic dysfunction; the remaining 11 patients with a normal E/A ratio constituted the control group. Afterward, the data recorded before the cardioversion were analyzed for each patient. In
Left ventricular (LV) diastolic function can be assessed noninvasively by analysis of the pulsed Doppler mitral flow velocity pattern. In patients with sinus rhythm, simple Doppler indexes such as the ratio of mitral peak early diastolic flow velocity (E) to mitral peak flow velocity at atrial contraction (A) is usually sufficient for the diagnosis of LV diastolic dysfunction.1-9 This ratio, however, is not obtainable in patients with atrial fibrillation (AF) because of the lack of a synchronized atrial contraction. Therefore investigators tried to discover other parameters that could be used as a marker of diastolic dysfunction in patients with AF. In patients with sinus rhythm, it has been demonFrom the Departments of Cardiology and Emergency Medicine, Dokuz Eylul University Hospital, Inciralti, Izmir, Turkey. Reprint requests: Cem Nazli, MD, Mustafa Bey Cad No 12/6, Alsancak, 35220, Izmir, Turkey. Copyright © 1998 by the American Society of Echocardiography. 0894-7317/98 $5.00 + 0 27/1/93439
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subjects with normal diastolic function, the peak diastolic flow velocity (PDFV) at the mitral tips also was maintained at the positions 1 to 3 cm away from the tip in the left ventricular cavity (PDFV at the mitral tips: 0.84 m/s, PDFV at 3 cm: 0.85 m/s; P = .34). In contrast, the regional PDFV progressively decreased toward the apex in patients with diastolic dysfunction (PDFV at the mitral tips: 0.82 m/s, PDFV at 3 cm: 0.63 m/s; P = .0004). Only 77% of the initial velocity was maintained at 3 cm away from the mitral tips in patients with diastolic dysfunction, whereas almost 100% of the initial velocity was preserved in patients with normal diastolic function (P < .001). These findings suggest that the assessment of the intraventricular decrease in mitral PDFV may be used as a reliable marker of diastolic dysfunction in patients with atrial fibrillation. (J Am Soc Echocardiogr 1998;11:1036-43.)
strated that the regional peak diastolic flow velocity (PDFV) progressively decreases toward the apex in patients with diastolic dysfunction, whereas it is maintained throughout the LV cavity in patients with normal diastolic function.10 It has been suggested, but not yet proven, that this finding also can be used to assess LV dysfunction in patients with AF. This study was designed to elucidate whether the intraventricular dispersion of early diastolic filling velocity can be used as a reliable marker of diastolic dysfunction in patients with AF.
METHODS Fifty-two consecutive patients who were considered for conversion of AF to sinus rhythm in the Cardiology Department of Dokuz Eylul University Hospital from November 1996 to June 1997 were evaluated both clinically and echocardiographically before cardioversion.
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Exclusion criteria included a history or echocardiographic evidence of coronary artery disease (angina pectoris, prior myocardial infarction, LV wall motion abnormalities), valvular heart disease (mitral stenosis, aortic stenosis, moderate or severe aortic or mitral regurgitation), congestive heart failure (New York Heart Association functional class greater than 2 or signs of heart failure at physical examination, LV dilatation, ejection fraction < 50%), restrictive cardiomyopathy, idiopathic dilated cardiomyopathy, and pericardial disease (constrictive pericarditis, pericardial effusion). Six patients with coronary artery disease, 3 patients with mitral stenosis, 1 patient with aortic stenosis, 4 patients with moderate or severe aortic regurgitation, 6 patients with moderate or severe mitral regurgitation, 3 patients with congestive heart failure, 1 patient with idiopathic dilated cardiomyopathy, and 1 patient with pericardial effusion were excluded from the study. The study population consisted of 27 patients (15 women, 12 men; mean age 59.5 years) with nonvalvular atrial fibrillation who were converted to sinus rhythm either medically or by electrical cardioversion. Hypertension was present in 18 patients and LV hypertrophy was demonstrated in 5 patients.Twelve patients had minimal mitral regurgitation and 3 patients had minimal aortic regurgitation. Mitral valve prolapse was present in 3 patients and mitral annular calcification was detected in 4 patients. No other cardiovascular disease was observed in the whole study group. All patients gave informed consent for participation. Elective cardioversion of AF was accomplished pharmacologically in 13 patients with propafenone (600 mg, single oral dose) and with direct-current cardioversion (mean 1.9 shocks, mean 225 ± 85 J for success) in 14 patients, all of whom initially had no success with oral propafenone. The patients received no other antiarrhythmic medication for pharmacologic cardioversion. The duration of atrial fibrillation was determined either clinically by an abrupt, well-defined, onset of palpitations with subsequent electrocardiographic evidence of AF or only by electrocardiographic documentation during hospitalization.The duration of AF was unknown in 14 patients. The estimated duration of AF was less than 6 weeks in all patients with known duration of AF. Patients with an AF of more than 48 hours (4 patients) or with unknown duration of AF (14 patients) were examined with transesophageal echocardiography before electrical or medical cardioversion. None of the patients was found to have thrombus in the left atrium or left atrial appendage. All of these patients received anticoagulation therapy for 1 month after cardioversion. After successful cardioversion (either medical or electrical), all patients were discharged and received oral amiodarone therapy for the maintenance of the sinus rhythm. Atrial fibrillation relapsed in 3 patients, however, (all of whom had unknown duration of AF, and 1 patient had
Kozan et al 1037
Figure 1 Method of analysis of peak diastolic flow velocities within left ventricular cavity from apical 4-chamber view. Ultrasound beam is aligned parallel to mitral diastolic color Doppler flow. LA, Left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.
hypertension) during the follow-up period and these patients were excluded from the study. None of the patients had cerebrovascular events or other clinically evident arterial embolism immediately after cardioversion or during the follow-up period. The first transthoracic Doppler echocardiographic examination (ECHO 1) was performed before cardioversion.The echocardiographic recordings were obtained with the patients in the left lateral decubitis position. A commercially available echocardiograph (Accuson 128, Acuson Corporation, Mountain View, Calif) with a 2.5-MHz probe was used to record pulsed Doppler diastolic flow velocity patterns. Initially, the diastolic flow velocity pattern at the mitral tip was recorded. The mitral flow velocity pattern was obtained in the standard apical 4-chamber view with a sample volume placed between the tips of the mitral leaflets. The recordings of the regional pulsed Doppler diastolic flow velocity patterns at 1, 2 and 3 cm from the mitral tip toward the apex were subsequently obtained with minimal delay.The depth of each sample was 2 mm. The ultrasound beam was aligned as parallel to the flow as possible with the guidance of color Doppler flow imaging (Figure 1). No angle correction was made in the calculation of velocity from the Doppler signals. All recordings were performed during brief apnea at end-expiration to avoid the effects of respiratory variation. The mitral and regional flow velocity patterns at 1, 2 and 3 cm from the mitral tip toward the apex were traced along the darkest portion of the velocities to obtain the peak early diastolic flow velocities. The ratio of regional PDFV to mitral PDFV was calculated by averaging the val-
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Table 1 Comparison of the baseline characteristics of the patients Diastolic dysfunction (n = 13)
Normal (n = 11)
P
Sex (N, %): Men 4 (30.7) 5 (45.5) .45 Women 9 (69.3) 6 (54.5) Age 60 ± 5.7 59 ± 7.1 .18 Heart Rate (beats/min): ECHO 1 86.5 ± 7.5 89.1 ± 9 .45 ECHO 2 72 ± 5.8 73.1 ± 6.8 .60 LV dimensions: End-diastolic diameter 5.1 ± 0.37 4.9 ± 0.38 .17 (cm) End-systolic diameter 2.9 ± 0.25 3.0 ± 0.19 .068 (cm) EF (%) 62.4 ± 5.1 61.8 ± 6.3 .79 HT (%) 11 (84) 6 (54.5) .18 LV hypertrophy (%) 5 (38) 0 (0) < .05 Duration of AF (days) 8.1 ± 5.8 7 ± 10.4 .80 (in patients with known duration of AF) Patients with unknown 7 (53) 4 (36) .39 duration of AF (%) Time between cardioversion 19.3 ± 11.9 15.3 ± 11.6 .41 and ECHO 2 (days) ECH0 1, Transthoracic Doppler echocardiographic examination before cardioversion; ECHO 2, transthoracic Doppler echocardiographic examination after cardioversion; EF, ejection fraction; HT, hypertension; LV, left ventricle.
ues of 10 consecutive cardiac cycles. The interobserver and intraobserver variabilities of the measurement of flow velocities were not calculated because these variabilities in the measurement of mitral peak early diastolic flow velocity have been shown previously to be negligible.11 Full recovery of left atrial mechanical functions has been shown to be achieved within 1 week in patients with brief (< 2 weeks) and moderate (2-6 weeks) duration of AF and within 1 month in patients with prolonged (> 6 weeks) AF.12 Therefore the second transthoracic Doppler echocardiographic examination (ECHO 2) of patients with known duration of AF was performed 1 week after cardioversion. On the other hand, the second Doppler echocardiographic study was obtained 1 month after cardioversion in patients with unknown duration of AF. Patients with unknown duration of AF actually comprise patients with both brief and prolonged duration of AF. All of these patients, however, were assumed to have a prolonged duration of AF and the second echocardiographic examination was performed at 30 days.Thus even if some patients had experienced a brief duration of AF, the full recovery of left atrial mechanical functions in these patients was probably achieved more securely at 30 days. In the ECHO 2 examination, the mitral flow velocity pattern was obtained in the standard apical 4-chamber view
with the sample volume placed at the mitral tips. Patients with an E/A ratio of less than 1 were assumed to have LV diastolic dysfunction. Twenty-two patients received digoxin for pharmacologic control of the ventricular rate of AF before cardioversion. Use of digoxin was stopped in all patients after they converted to sinus rhythm. Patients with hypertension (17 patients) were receiving angiotensin-converting enzyme (ACE) inhibitors (lisinopril, enalapril, or fosinopril) (9 patients), indapamide (3 patients), verapamil (1 patient), diltiazem (1 patient) and metoprolol (1 patient) both before cardioversion and during the ECHO 2 examination after cardioversion. Two patients with hypertension were not on any antihypertensive medication. Statistical Analysis Values are expressed as mean ± standard deviation.The statistical significance of the difference in the data among the groups was tested by using the chi-square test for the discrete variables and unpaired t test for continuous variables. A P value of less than .05 was considered to be statistically significant.
RESULTS Thirteen patients were found to have diastolic dysfunction, whereas 11 patients demonstrated normal diastolic flow velocity pattern in the ECHO 2 examination. No significant difference was noted between the 2 groups with regard to age, sex, ejection fraction, LV dimensions, heart rate, and hypertension, but patients with diastolic dysfunction had a higher rate of LV hypertrophy (Table 1). The duration of AF before cardioversion (in patients with known duration of AF) was similar for both groups (patients with diastolic dysfunction: 8.1 ± 5.87 days, patients with normal diastolic function: 7 ± 10.4 days; P = .80).The number of patients with unknown duration of AF was higher in the group with diastolic dysfunction than in the normal group, but the difference was not statistically significant (53% versus 36%, respectively; P = .39). No statistically significant difference was found between patients with abnormal and normal diastolic function with regard to time interval between cardioversion and the second echocardiogram (19.3 ± 11.9 days versus 15.3 ± 11.6 days, respectively; P = .41) (Table 1). In subjects with normal diastolic function, the PDFV at the level of mitral tips (E0) and regional peak diastolic flow velocities at 1 cm (E1), 2 cm (E2) and 3 cm (E3) away from the tips that were recorded in the Doppler examination before the cardioversion
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Kozan et al 1039
Figure 2 Intraventricular peak diastolic flow velocity profile of patients before cardioversion. E(0), Peak mitral diastolic flow velocity at the mitral tip; E(1), peak mitral diastolic flow velocity at 1 cm away from the mitral tip; E(2), peak mitral diastolic flow velocity at 2 cm away from the mitral tip; E(3), peak mitral diastolic flow velocity at 3 cm away from the mitral tip.
Table 2 Comparison of the peak diastolic flow velocity at mitral tips with the regional peak diastolic velocities in patients with and without diastolic dysfunction Diastolic dysfunction
E0 (m/s) E1 (m/s) P E0 (m/s) E2 (m/s) P E0 (m/s) E3 (m/s) P
0.82 ± 0.83 ± .37 0.82 ± 0.73 ± .004 0.82 ± 0.63 ± .0004
0.17 0.16 0.17 0.16 0.17 0.16
Table 3 The ratios of regional peak diastolic flow velocities to E0 in patients with and without diastolic dysfunction
Normal diastolic function
0.84 ± 0.89 ± .039 0.84 ± 0.87 ± .20 0.84 ± 0.85 ± .36
0.25 0.25 0.25 0.25 0.25 0.27
E0, Peak mitral diastolic flow velocity at mitral tip; E1, peak mitral diastolic flow velocity at 1 cm away from mitral tip; E2, peak mitral diastolic flow velocity at 2 cm away from mitral tip; E3, peak mitral diastolic flow velocity at 3 cm away from mitral tip.
were as follows: E0 = 0.84 ± 0.25 m/s, E1 = 0.89 ± 0.25 m/s, E2 = 0.87 ± 0.25 m/s, E3 = 0.85 ± 0.27 m/s. In other words, the E wave velocity was maintained even at positions 1 to 3 cm away from the tip into the LV cavity. On the other hand, the early diastolic flow velocity decreased progressively from the mitral tip to the apex in patients with diastolic dysfunction (E0 = 0.82 ± 0.17 m/s, E1 = 0.83 ± 0.16 m/s, E2 = 0.73 ± 0.16 m/s, E3 =0.63 ± 0.16 m/s) (Figure 2). In patients with normal diastolic function, the comparison of PDFV at the mitral tip with the regional peak diastolic velocities revealed a significant acceleration at 1 cm (P = .039) but no significant differences at 2 cm and 3 cm from the mitral tip toward apex (P = .20, P = .36, respectively). On the other hand, E0 was significantly higher than E2 and E3
E1/E0 E2/E0 E3/E0
Diastolic dysfunction (n = 13)
Normal diastolic function (n = 11)
P
1.01 ± 0.10 0.90 ± 0.11 0.77 ± 0.17
1.06 ± 0.10 1.05 ± 0.19 1.01 ± 0.11
.21 .03 < .001
E0, Peak mitral diastolic flow velocity at mitral tip; E1, peak mitral diastolic flow velocity at 1 cm away from mitral tip; E2, peak mitral diastolic flow velocity at 2 cm away from mitral tip; E3, peak mitral diastolic flow velocity at 3 cm away from mitral tip.
in patients with diastolic dysfunction (P = .004, P = .0004, respectively) . The statistical significance of the difference was greatest at 3 cm from the mitral tips toward the apex (Table 2). The intraventricular decrease in diastolic flow velocity was quantified with the ratios of regional peak early diastolic flow velocity at 1, 2, and 3 cm from the mitral tip toward the apex to the E0. A progressive decrease in the ratio of the regional PDFV to E0 was observed in patients with diastolic dysfunction. In contrast, the PDFV profile was preserved throughout the LV cavity in the patients without diastolic dysfunction (Figure 3).The ratios at 2 and 3 cm away from the mitral tip were significantly smaller in patients with diastolic dysfunction than in the subjects with normal diastolic function (P = .03, P < .001, respectively) (Table 3). Only 77% of the initial velocity was maintained at 3 cm away from the mitral tips in patients with diastolic dysfunction, whereas almost 100% of the initial velocity was preserved in patients with normal diastolic function (P < .001).
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Figure 3 Comparison of the ratio of regional peak diastolic flow velocity to E0 among subjects with normal LV diastolic function and patients with diastolic dysfunction.
DISCUSSION Left ventricular diastolic performance is mainly dependent on 2 discrete factors: relaxation and compliance. During diastole, the left ventricle must receive an adequate filling volume while maintaining low intracavitary pressures. To accomplish this, the ventricular myocardium relaxes during early diastole and the walls distend readily, allowing the chamber to receive a wide range of inflow volumes at low filling pressures. The stiffness of the LV chamber depends on the passive elastic properties of the myocardium, the thickness of the ventricular wall, the geometry of the chamber, the interaction between the 2 ventricles, and the intrapericardial pressure.13 To ensure optimal diastolic filling, the left atrium also contracts before ventricular activation. Doppler echocardiography can be used as a noninvasive, easily performed and reliable method for the evaluation of diastolic performance. In the presence of slower LV relaxation but with otherwise normal chamber stiffness and filling pressures, the isovolumic relaxation time increases in response to a slower rate of LV pressure decay.8,14,15 After mitral valve opening, the rate of pressure decline slows down even further, and because the left atrial pressure is low, the transmitral pressure gradient is diminished. This results in a reduced rate of LV filling, a decline in E velocity, and a prolongation of deceleration time. The reduction in early filling and consequently in early atrial emptying produced by delayed
LV relaxation causes the atrium to have a relatively higher volume before its contraction, which results in a more vigorous contraction, with increased velocity accounting for the accentuated A wave. In summary, the typical pattern of mitral inflow velocity associated with delayed LV relaxation consists of an E/A ratio of less than 1, an increase in the deceleration time, a prolonged isovolumic relaxation time, and a relative increase in the atrial filling fraction. On the other hand, these parameters are affected by various factors such as age, heart rate, loading conditions, systolic dysfunction, and valvular insufficiencies. In addition, the E/A ratio and atrial filling fraction cannot be obtained in patients with AF. All these facts have led investigators to seek other reliable parameters that can be used for the assessment of LV diastolic dysfunction in patients with AF. Regional micromanometric LV pressure measurements in animal models have demonstrated an early diastolic positive intraventricular pressure gradient from base to apex in normal hearts.16 Courtois et al17 have also shown that this positive pressure gradient is lost or reversed in the presence of LV dysfunction. Beppu et al18 demonstrated in an animal experiment that contrast medium injected into the left atrium reached the LV apex in one diastole in normal hearts and did not reach the apex after coronary ligation. Their data suggest that early diastolic flow velocity is rapidly decelerated in the presence of LV systolic and diastolic dysfunction.The positive intraventricular pressure gradient is considered to
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maintain or accelerate the velocity of the early diastolic flow toward the apex, so its loss will result in progressive deceleration of the velocity within the LV cavity. Investigators have proposed that the loss of the intraventricular pressure gradient due to LV dysfunction may result mainly from the impairment of LV diastolic function. Color Doppler studies supporting this hypothesis have demonstrated that the velocity of LV diastolic flow propagation measured with color M-mode Doppler echocardiography decreases progressively from mitral tip to apex in the presence of LV diastolic dysfunction.19-21 Yamamato et al10 have suggested that the assessment of the intraventricular diastolic flow velocity profile may provide useful information about the LV diastolic functions, considering that the intraventricular diastolic flow velocity profile is altered in the presence of LV diastolic dysfunction. These researchers have demonstrated that the early diastolic flow velocity decreases progressively from the mitral tip into the LV cavity in patients with diastolic dysfunction, whereas the E value was maintained even at 1 to 3 cm away from the tip in healthy subjects, all of whom were in sinus rhythm. Similarly, the E value was maintained in the LV cavity in patients with isolated AF, whereas a marked intraventricular decrease in the PDFV was observed in the patients with AF and hypertension or dilated cardiomyopathic conditions who were assumed to have diastolic dysfunction. On the other hand, these patients were not converted into sinus rhythm and reevaluated for the presence of classical Doppler indexes of LV diastolic dysfunction. Currently it is still unclear whether the intraventricular dispersion of the early diastolic filling can be used as a reliable marker of LV diastolic dysfunction in patients with AF. We have shown that patients with AF and progressive intraventricular decrease in diastolic flow velocity demonstrated a typical pattern of diastolic dysfunction in Doppler examination after conversion to sinus rhythm. In contrast, patients with AF and a preserved intraventricular diastolic flow velocity pattern revealed a normal pattern of mitral diastolic inflow. Therefore our results are in concordance with the data of the previous studies suggesting the use of intraventricular dispersion of diastolic flow velocity in the assessment of diastolic dysfunction in patients with AF. Thus far, this is the first study demonstrating that the diastolic dispersion can be used as a reliable indicator of diastolic dysfunction in patients with AF. Our results also indicate that the measurement of the decrease at 3 cm from the mitral tip is enough to detect LV diastolic dysfunction, con-
Kozan et al 1041
sidering that the decrease in PDFV is highest at this point. The mechanism of acceleration of diastolic flow at 1 cm from the mitral tips in patients with normal diastolic function is unclear. It may be caused by the greater suctioning effect of LV relaxation at this point, because the diastolic excursion of LV walls is highest at this region.22 The alignment of the ultrasound beam exactly parallel to the stream line is crucial for the accurate measurement of regional PDFV. Color Doppler imaging was used for appropriate alignment of the ultrasound beam, but some errors may still exist in the acquisition of Doppler data, especially in cases in which obtaining a clear apical 4-chamber view was difficult. Aortic regurgitant flow is considered to alter diastolic intraventricular flow dynamics. The intraventricular diastolic flow stream is not straight in patients with regional wall motion abnormalities, so the ultrasound beam cannot be oriented parallel to the stream at all positions within the LV cavity. Therefore, measurement of the intraventricular decrease in PDFV cannot be used to assess LV diastolic dysfunction in patients with moderate or severe aortic regurgitation and LV regional wall motion abnormalities. It has been proposed that LV systolic dysfunction and LV enlargement might also account for the intraventricular dispersion of diastolic flow velocity.10,23 Early diastolic events in the left ventricle generally are regulated by LV relaxation and elastic recoil, and because the LV size and systolic functions are important determinants of these factors, LV dilation and systolic dysfunction may be associated with the loss of the positive intraventricular pressure gradient. Because LV systolic functions and diameters were normal in all of our patients, the progressive intraventricular decrease in PDFV in these patients was most likely attributable to LV diastolic dysfunction. Mitral flow velocity pattern is known to be affected by LV diastolic function and by loading conditions.7,9,24-27 Abnormal loading conditions may lead to a normalized pattern and some patients with diastolic dysfunction may be falsely regarded as “normal” in Doppler echocardiography. Loading conditions also may affect the intraventricular pressure gradient and hence the intraventricular diastolic flow velocity profile. In this study, the intraventricular pressure gradient was not measured and the relation between the intraventricular decrease in PDFV and intraventricular pressure gradient has not been demonstrated. Such a relationship is still hypothetical and it should
1042 Kozan et al
be documented with future studies by the use of high-fidelity manometer-tipped catheters for intraventricular pressure gradient measurement in animal and human models. The most important limitation of our study is the small number of patients, because of the difficulties in finding such a select group of patients fulfilling the inclusion criteria. Therefore these findings should be confirmed with future studies that include a larger number of patients. Certain medications, particularly calcium channel blockers, can affect measurements of diastolic function and therefore interfere with the interpretation of Doppler indices of diastolic function. ACE inhibitors and indapamide might also have some beneficial effects on diastolic function, possibly by reducing the LV mass.28 On the other hand, these drugs might also reverse the intraventricular dispersion of the PDFV as well as the mitral diastolic indices (ie, E/A ratio) by improving diastolic functions. For example, a patient with a normalized E/A ratio caused by chronic usage of calcium channel blockers or ACE inhibitors might also have no intraventricular dispersion of PDFV before cardioversion.This issue should be clarified with further studies. The assumption that the A wave necessarily reflects LV compliance and therefore diastolic function may result in a methodologic limitation. It may also reflect the force of atrial contraction and these may affect the interpretation of the measurements taken during the second echocardiographic examination. Although current data suggest that full recovery of left atrial mechanical functions is achieved within 1 week in patients with brief and moderate duration of AF and within 1 month in patients with prolonged AF,12 a few exceptional cases may still have incomplete recovery of atrial mechanical functions at this period. The peak A velocity may increase later as the force of atrial contraction increases and thus alter the E/A ratio. Abnormalities of LV compliance may be better demonstrated with gated radionuclide angiography and micromanometer pressure recordings, which reflect LV lusitropy independent of left atrial mechanical functions.29,30 In conclusion, these findings suggest that a progressive intraventricular decrease in peak early diastolic flow velocity mainly reflects LV diastolic dysfunction. Further investigations are necessary to assess the contribution of other factors to intraventricular dispersion of early diastolic filling. Our findings suggest that the intraventricular dispersion of early diastolic filling may be used as a reliable mark-
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er of diastolic dysfunction in patients with AF, but this should be confirmed with further studies. REFERENCES 1. Masuyama T, Kodama K, Nakatani S, Kitabatake A, Kamada T. Effects of changes in coronary stenosis on left ventricular diastolic filling assessed with pulsed Doppler echocardiography. J Am Coll Cardiol 1988;11:744-51. 2. Stoddard MF, Pearson AC, Kern MJ, Ratcliff J, Mrosek DG, Labovitz AJ. Left ventricular diastolic function: comparison of pulsed Doppler echocardiographic and hemodynamic indexes in subjects with and without coronary artery disease. J Am Coll Cardiol 1989;13:327-36. 3. Maron BJ, Spirito P, Green KJ, Wesley YE, Bonow RO, Arje J. Non-invasive assessment of left ventricular diastolic function by pulsed Doppler echocardiography in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 1987;10: 733-42. 4. Takenaka K, Dabestain A, Gardin JM, et al. Pulsed Doppler echocardiographic study of left ventricular filling in dilated cardiomyopathy. Am J Cardiol 1986;58:143-7. 5. Phillips CA, Coplan NL, Krakoff LR, et al. Doppler echocardiographic analysis of left ventricular filling in treated hypertensive patients. J Am Coll Cardiol 1987;9:317-22. 6. Kitabatake A, Inoue M, Asao M, et al. Transmitral blood flow reflecting diastolic behavior of the left ventricle in health and disease: a study by pulsed Doppler technique. Jpn Circ J 1982;46:92-102. 7. Vanoverschelde JLJ, Raphael DA, Robert AR, Cosyns JR. Left ventricular filling in dilated cardiomyopathy: relation to functional class and hemodynamics. J Am Coll Cardiol 1990; 15:1288-95. 8. Appleton CP, Hatle LK, Popp RL. Relation of transmitral flow velocity patterns to left ventricular diastolic function: new insights from a combined hemodynamic and Doppler echocardiographic study. J Am Coll Cardiol 1988;12:426-40. 9. St Goar FG, Masuyama T, Alderman EL, Popp RL. Left ventricular diastolic dysfunction in end-stage dilated cardiomyopathy: simultaneous Doppler echocardiography and hemodynamic evaluation. J Am Soc Echocardiogr 1991;4:349-60. 10. Yamamato K, Masuyama T, Tanouchi J, et al. Intraventricular dispersion of early diastolic filling: A new marker of left ventricular diastolic dysfunction. Am Heart J 1995;129:291-9. 11. Yamamato K, Masuyama T, Tanouchi J, et al. Peak early diastolic filling velocity may decrease with preload augmentation: effect of concomitant increase in a rate of left atrial pressure drop in early diastole. J Am Soc Echocardiogr 1993;6: 245-54. 12. Manning WJ, Silverman DI, Katz SE, et al. Impaired left atrial mechanical function after cardioversion: relationship to the duration of atrial fibrillation. J Am Coll Cardiol 1994;23: 1535-40. 13. Quinones M. Doppler assessment of left ventricular diastolic function. In: Nanda NC, editor. Doppler echocardiography. 2nd edition. Philadelphia: Lea & Febiger; 1993. p. 197-215. 14. Nishimura RA, Abel MD, Hatle LK, et al. Assessment of diastolic dysfunction of the heart: Background and current applications of Doppler echocardiography. Part II. Clinical studies. Mayo Clin Proc 1989 64:181-204. 15. Chen W, Gibson D. Relation of isovolumic relaxation to left
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24. Yamamato K, Masuyama T, Tanouchi J, et al. Importance of left ventricular minimum pressure as a determinant of transmitral flow velocity pattern in the presence of left ventricular systolic dysfunction. J Am Coll Cardiol 1993;21:662-72. 25. Thomas JD, Choong CYP, Flachskampf FA, Weyman AE. Analysis of the early transmitral Doppler velocity curve: effect of primary physiologic changes and compensatory preload adjustment. J Am Coll Cardiol 1990;16:644-55. 26. Choong CY, Abascal VW, Thomas JD, Guerrero JL, McGlew S, Weyman AE. Combined influence of ventricular loading and relaxation on the transmitral flow velocity profile in dogs measured by Doppler echocardiography. Circulation 1988; 78:672-83. 27. Masuyama T, St Goar FG, Alderman EL, Popp RL. Effects of nitroprusside on transmitral flow velocity patterns in extreme heart failure: a combined hemodynamic and Doppler echocardiographic study of varying loading conditions. J Am Coll Cardiol 1990;16:1175-85. 28. Bonow RO, Udelson JE. Left ventricular diastolic dysfunction as a cause of congestive heart failure. Mechanisms and management. Ann Intern Med 1992;117:502-10. 29. Bonow RO, Bacharach SL, Green MV, et al. Impaired left ventricular diastolic filling in patients with coronary artery disease: assessment with radionuclide angiography. Circulation 1981;64:315-23. 30. Magorien DJ, Shaffer P, Bush CA, et al. Assessment of left ventricular pressure-volume relations using gated radionuclide angiography, echocardiography, and micromanometer pressure recordings. A new method for serial measurements of systolic and diastolic function in man. Circulation 1983; 67:844-53.
Availability of Back Issues As a service to our subscribers, copies of back issues of Journal of the American Society of Echocardiography for the preceding 5 years are maintained and are available for purchase from the publisher, Mosby, at a cost of $16.00 per issue. The following quantity discounts are available: 25% off on quantities of 12 to 23, and one third off on quantities of 24 or more. Please write to Mosby, Inc, Subscription Services, 11830 Westline Industrial Dr, St Louis, MO 63146-3318, or call (800) 453-4351 or (314) 453-4351 for information on availability of particular issues. If unavailable from the publisher, photocopies of complete issues are available from University Microfilms International, 300 N Zeeb Rd, Ann Arbor, MI 48106, (313) 761-4700.