Echokardiographische Diagnostik der diastolischen Herzinsuffizienz

BACKGROUND: Left ventricular diastolic dysfunction can be diagnosed if clinical signs of heart failure and normal ejection fraction are found. Beside clinical signs of heart failure and criteria from catheterization studies like abnormal left ventricular relaxation, filling and/or compliance echocardiography provides valuable parameters for the assessment of diastolic dysfunction. ECHOCARDIOGRAPHIC DEGREES OF SEVERITY: By the use of various parameters diastolic dysfunction can be differentiated into four degrees of severity, which are of great prognostic importance. If more than one echocardiographic parameter is used, sensitivity for the assessment of diastolic dysfunction becomes nearly 100%. Conventional parameters include isovolumetric relaxation time (IVRT) measured by pulsed Doppler, the ratio of rapid filling and atrial filling velocity (E/A), deceleration time of rapid mitral inflow as well as the ratio of systolic and diastolic pulmonary venous flow velocities. In patients with signs of diastolic heart failure and a normal E/A ratio pulmonary venous flow pattern can help to unmask "pseudonormalization" as the transition from abnormal relaxation to restriction. These parameters, however, are preload-dependent and do not provide intrinsic left ventricular properties. Even in atrial fibrillation, left ventricular filling pressure can be assessed. NEW METHODS: Two novel approaches, color Doppler M-mode of left ventricular inflow and tissue Doppler of the mitral annulus, are relatively preload-independent and allow direct estimation of relaxation and filling pressure. By the means of real-time 3-D echocardiography we developed a new method for the non-invasive assessment of rapid filling rate (PFR), thereby completing the echocardiographic approaches to determine diastolic dysfunction. CONCLUSION: The broad spectrum of approaches available today makes echocardiography the first choice for the assessment of diastolic dysfunction.     

Factors affecting parameters of left ventricular diastolic function derived from Doppler echocardiography

According to the data from left ventricular catheterization as well as M-mode and two-dimensional echocardiography in 36 patients, the influence of left ventricular diameter, systolic function, systolic and diastolic filling pressures on the parameters of left ventricular diastolic function derived from Doppler echocardiography was analysed. The results indicate: (1) the left ventricular end diastolic pressure, rapid filling wave pressure and the ratio of the both significantly affect the Doppler diastolic function parameters; (2) the decrease of the ratio of early-to-late diastolic mitral flow velocities (E/A) is only a manifestation of early stage of left ventricular diastolic dysfunction and the E/A ratio returns to normal (false improving) at advanced stage of left ventricular diastolic dysfunction.     

Regional Left Ventricular Diastolic Dysfunction Evaluated by Pulsed-Tissue Doppler Echocardiography

Pulsed-wave Doppler tissue imaging (DTI) allows the examination of regional wall motion at a very high temporal resolution and therefore constitutes an excellent technique for assessing diastolic motion of left ventricular walls. Regional relaxation has been well characterized in normal subjects using this technique, and physiological time intervals and motion wave profiles are described. In an experimental model of acute ischemia, local relaxation impairment was observed showing highly characteristic local diastolic abnormalities. Interestingly, these findings took place before any decrease in systolic motion was recordable. In a prospective clinical study, noninvasive regional DTI parameters were compared with coronary angiography to assess the feasibility and clinical value of the technique; the diagnostic accuracy is discussed in detail. Also, the association between regional diastolic parameters and global regional function as assessed by Doppler analysis of transmitral left ventricular filling flow was studied, stressing the impact of regional diastolic function on overall ventricular performance. Finally, the diagnostic role of pulsed-wave DTI on stress testing, identification of myocardial viability, and microvascular angina is reviewed.     

Diastolic Ventricular Interaction and Ventricular Diastolic Filling

Because the ventricles share a common septum, the filling of one may influence the compliance of the other, a phenomenon known as direct diastolic ventricular interaction (DVI). This interaction is markedly enhanced when the force exerted by the surrounding pericardium is raised (pericardial constraint). In health, in the resting state, we operate near the top of the flat component of a J-shaped pericardial stress–strain relation. Therefore, pericardial constraint (and hence DVI) is only minor. When right ventricular volume/pressure acutely increases, such as during exercise, massive pulmonary embolism, or right ventricular infarction, pericardial constraint increases and significant DVI develops. In this setting, the measured left ventricular intracavitary diastolic pressure markedly overestimates the true left ventricular filling pressure, because the external forces must be subtracted. Although the pericardium can grow during chronic cardiac enlargement, we present evidence that in certain chronic disease processes, including heart failure, DVI may also be important.     

The role of Doppler echocardiography in the assessment of left ventricular diastolic function

The role of Doppler echocardiography of transmitral filling velocities in the assessment of diastolic function in man has not been adequately defined. It is now appreciated that multiple interacting factors such as loading conditions influence the transmitral velocity profile independent of intrinsic left ventricular diastolic function. Extrapolating the status of diastolic function from the transmitral velocity profile is complicated by these factors. The load dependence of ventricular filling has tempered the initial enthusiasm for the clinical application of the Doppler technique. In the present review, studies examining invasive parameters of diastolic function and Doppler indices of diastolic filling are discussed to gain greater insight and understanding of the role of Doppler echocardiography in the noninvasive assessment of diastolic function. These studies have demonstrated a relatively consistent influence of left ventricular relaxation, chamber stiffness, and left atrial pressure on the transmitral velocity filling profile. Impairment of relaxation impedes early filling and may result in a compensatory increase in atrial contribution to filling. An independent decrease in left atrial pressure from altered loading conditions may also reduce filling in early diastole. Increased left ventricular chamber stiffness (i.e., noncompliant left ventricle) impairs atrial contribution to filling and may enhance early filling. Theoretically, reduced left atrial contractility may decrease atrial contribution to filling. Pulmonic vein flow demonstrating increased retrograde flow during atrial systole helps to exclude impaired left atrial contractility. An increased left atrial pressure from altered loading conditions may also augment early filling. Therefore, an invasive or clinical assessment of left atrial pressure as being increased, decreased, or normal greatly aids in the interpretation of the transmitral filling velocity profile when inferences on the status of diastolic function are being made. Diastolic dysfunction is likely when a given pattern of filling cannot be explained on the basis of left atrial pressure. In situations where reasonable estimates on the status of left atrial pressure cannot be done, striking alterations in the transmitral velocity filling profile may be useful.     

Tissue Doppler imaging in the evaluation of left ventricular diastolic function

PURPOSE OF REVIEW: Describe the rationale behind, and clinical use of, tissue Doppler (TD) imaging in the assessment of left ventricular (LV) diastolic function, with a focus on recent developments. RECENT FINDINGS: Tissue Doppler imaging is a novel echocardiographic technique that directly measures myocardial velocities. Systolic TD measurements assess left and right ventricular myocardial contractile function. Diastolic TD values reflect myocardial relaxation, and in combination with conventional Doppler measurements, ratios (E/Ea) have been developed to estimate LV filling pressures. TD values and derived ratios have been demonstrated to be valuable in the diagnosis of elevated LV filling pressures, clinical congestive heart failure (CHF), and the prognosis of patients with cardiac disease and CHF. New TD indices have now been developed to assess myocardial relaxation and LV filling pressures, and the impact of LV systolic function on the use of TD imaging has recently been described. TD echocardiography is being used in an ever-widening group of patients for the assessment of LV diastolic function, and its correlation to, and comparison with, B-type natriuretic peptide is an active area of current investigation. SUMMARY: This review focuses on new developments in the clinical use of TD echocardiography in the evaluation of left ventricular diastolic function.     

Comparison of left atrial volume parameters in detecting left ventricular diastolic dysfunction versus tissue Doppler recordings

Because of diastolic coupling between the left atrium and left ventricle, we hypothesized that left atrial (LA) function mirrors the diastolic function of left ventricle. The aims of this study were to assess whether LA volume parameters can be good indexes of left ventricular diastolic dysfunction. Six hundred fifty-nine patients underwent cardiac catheterization and measurements of left ventricular filling pressure (LVFP). Echocardiographic examinations including tissue Doppler and LA volumes were also assessed. Ratio of early diastolic mitral inflow velocity to early diastolic mitral annular velocity and LVFP tended to increase after progression of diastolic dysfunction. The inverse phenomenon existed in LA ejection and LA distensibility. LA distensibility was superior to LA ejection fraction and early diastolic mitral inflow velocity/early diastolic mitral annular velocity for identifying LVFP >15 mm Hg (areas under receiver operating characteristic curve 0.868, 0.834, and 0.759, respectively) and for differentiating pseudonormal from normal diastolic filling (areas under receiver operating characteristic curve 0.962, 0.907, and 0.741, respectively). Multivariate logistic regression showed that LA ejection fraction and LA distensibility were associated significantly with the presence of pseudonormal/restrictive ventricular filling. In conclusion, LA volume parameters can identify LVFP >15 mm Hg and differentiate among patterns of ventricular diastolic dysfunction. For assessing diastolic function LA parameters offer better performance than even tissue Doppler.     

Diastolic dysfunction in hypertension

Heart failure is one of the most common causes of cardiovascular morbidity and mortality, and hypertension is the most common cause of cardiac failure. Recent studies have shown that isolated diastolic dysfunction very often accompanies hypertensive heart disease. Ventricular diastolic function may be divided into an active relaxation phase and a passive compliance period. These two components have been investigated invasively, and they remain the gold standards for the study of diastolic function. However, in the routine clinical setting, echocardiographic and Doppler techniques are most useful for evaluating ventricular filling. Thus, analysis of E and A waves of mitral flow have provided important and useful information. Unfortunately, these indices depend on too many factors. Newer indices obtained from ventricular time intervals, tissue Doppler imaging, and color M-mode echocardiography have enhanced the means to assess diastolic function. In addition, new methods including MRI and cine CT have also provided better understanding of left ventricular filling in hypertension. Using these techniques, diastolic dysfunction has been found to be common in patients with hypertension, even before left ventricular hypertrophy is demonstrable and before hypertension in young, normotensive male offspring of hypertensive parents has developed. Furthermore, it has been made clear recently that myocardial ischemia and fibrosis are two important factors associated with diastolic dysfunction in hypertension.     

Using a Human Cardiopulmonary Model to Study and Predict Normal and Diseased Ventricular Mechanics, Septal Interaction, and Atrio-Ventricular Blood Flow Patterns

We upgraded our human cardiopulmonary (CP) model with additional data that enables it to more accurately simulate normal physiology. We then tested its ability to explain human disease by changing two parameter values that decrease ventricular compliance, and found that it could predict many of the hemodynamic, gas exchange, and autonomic abnormalities found in patients with left ventricular diastolic dysfunction (LVDD). The newly incorporated information includes high-fidelity pressure tracings simultaneously recorded from the RV and LV of a normal human in a cardiac catheterization laboratory, Doppler echocardiographic inlet flow velocity patterns, measures of right and left ventricular impedance, and atrial volumes. The revised cardiovascular section details the hemodynamics of a normal subject to the extent that it can now explain the effects of septal compliance on ventricular interaction, the differences in left and right ventricular pressure development, and venous blood gas mixing in the right atrium. The model can isolate the highly interrelated features of normal and abnormal physiology, and simultaneously demonstrate their interaction in a manner that would be very difficult or impossible using an intact organism. It may therefore help physicians and scientists understand, diagnose, and improve their treatment of complicated cardiovascular and pulmonary diseases. It could also simulate the hemodynamic and respiratory effects of ventricular and pulmonary assist devices, and thus help with their development.     

Noninvasive assessment of left ventricular diastolic function by pulsed Doppler echocardiography in patients with hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy is a primary myocardial disease in which symptoms may frequently result from impaired left ventricular relaxation, filling and compliance. In the present investigation, Doppler echocardiography was utilized to measure transmitral flow velocity and thereby assess left ventricular diastolic performance noninvasively in a group of 111 patients representative of the broad clinical spectrum of hypertrophic cardiomyopathy. In patients with hypertrophic cardiomyopathy, all Doppler indexes of diastolic relaxation and filling differed significantly (p less than 0.001) from those obtained in 86 control subjects without heart disease, namely, prolongation of isovolumic relaxation (94 +/- 24 versus 78 +/- 12 ms) and of the early diastolic peak of flow velocity (244 +/- 55 versus 220 +/- 28 ms), as well as slower deceleration (3.4 +/- 1.4 versus 4.9 +/- 1.3 m/s2) and reduced maximal flow velocity in early diastole (0.5 +/- 0.2 versus 0.6 +/- 0.1 m/s). As an apparent compensation for impaired relaxation and early diastolic filling, the atrial contribution to left ventricular filling was increased, as shown by increased late diastolic flow velocity (0.4 +/- 0.3 versus 0.3 +/- 0.1 m/s) and reduced ratio of maximal flow velocity in early diastole to that in late diastole (1.4 +/- 0.8 versus 2.1 +/- 0.9). The vast majority of patients with hypertrophic cardiomyopathy (91 [82%] of 111) showed evidence of impaired left ventricular diastolic performance, as assessed from the Doppler waveform. Abnormal Doppler diastolic indexes were identified with similar frequency in patients with (78%) or without (83%) left ventricular outflow obstruction, as well as in patients with (84%) or without (80%) cardiac symptoms. However, patients with nonobstructive hypertrophic cardiomyopathy showed more severe alterations in the Doppler indexes of diastolic function than did patients with obstruction. Thus, abnormal diastolic performance as assessed by Doppler echocardiography was apparent in the vast majority of the study patients with hypertrophic cardiomyopathy, independent of the presence or absence of cardiac symptoms or a subaortic pressure gradient. The high frequency with which diastolic abnormalities are identified in asymptomatic patients with hypertrophic cardiomyopathy suggests that impaired diastolic performance may be present at a time in the natural history of the disease when functional limitation is not yet evident.     

Demonstration of restrictive ventricular physiology by Doppler echocardiography

In patients with restriction of cardiac filling of various origins, cardiac catheterization has been traditionally used as part of the diagnostic evaluation to verify the presence of restrictive/constrictive hemodynamics. In an attempt to determine whether this "restrictive" physiology could be demonstrated noninvasively, 14 patients who had a history, physical examination, two-dimensional echocardiogram and catheterization data compatible with a restrictive myocardial process were studied with pulsed wave Doppler ultrasound. Forty normal subjects served as a control group. The Doppler ultrasound evaluation included measurement of peak mitral and tricuspid flow velocities and flow velocity integrals, mitral and tricuspid deceleration times and central venous flow patterns during apnea and inspiration. The flow velocity recordings across the mitral and tricuspid valves in patients manifesting restriction were markedly different from those in normal subjects, showing shortened deceleration times across both valves, which indicated both an abrupt premature cessation of ventricular filling and the presence of a diastolic dip-plateau contour in ventricular pressure recordings. In addition, abnormal central venous flow velocity reversals with inspiration and diastolic mitral and tricuspid regurgitation were frequently observed, also suggesting the reduced myocardial compliance characteristic of a restrictive myocardial process.     

Fluid dynamics model of mitral valve flow: description with in vitro validation

A lumped variable fluid dynamics model of mitral valve blood flow is described that is applicable to both Doppler echocardiography and invasive hemodynamic measurement. Given left atrial and ventricular compliance, initial pressures and mitral valve impedance, the model predicts the time course of mitral flow and atrial and ventricular pressure. The predictions of this mathematic formulation have been tested in an in vitro analog of the left heart in which mitral valve area and atrial and ventricular compliance can be accurately controlled. For the situation of constant chamber compliance, transmitral gradient is predicted to decay as a parabolic curve, and this has been confirmed in the in vitro model with r greater than 0.99 in all cases for a range of orifice area from 0.3 to 3.0 cm2, initial pressure gradient from 2.4 to 14.2 mm Hg and net chamber compliance from 16 to 29 cc/mm Hg. This mathematic formulation of transmitral flow should help to unify the Doppler echocardiographic and catheterization assessment of mitral stenosis and left ventricular diastolic dysfunction.     

Restrictive diastolic abnormalities identified by Doppler echocardiography in patients with thalassemia major

The consequences of transfusional iron overload on left ventricular diastolic filling have never been investigated systematically in patients with thalassemia major. In the present study, the pattern of left ventricular filling was assessed by Doppler echocardiography in 32 patients with thalassemia major (age, 17 +/- 5 years) who had not experienced symptoms of heart failure and had normal left ventricular systolic function. Data were compared with those obtained in 32 age-matched and sex-matched normal subjects. An abnormal Doppler pattern of left ventricular filling with increased flow velocity at mitral valve opening followed by an abrupt and premature decrease of flow velocity in early diastole was identified in the patients with thalassemia. Peak flow velocity in early diastole was increased in patients compared with controls (90 +/- 10 vs. 81 +/- 15 cm/sec; p less than 0.01), and rate of deceleration of flow velocity after the early diastolic peak and the ratio between the early and late (atrial) peaks of flow velocity were also increased (1,050 +/- 325 vs. 762 +/- 193 cm/sec2 and 2.7 +/- 0.7 vs. 2.2 +/- 0.5, respectively; p less than 0.001), whereas flow velocity deceleration time was reduced (97 +/- 22 vs. 119 +/- 19 msec; p less than 0.001). This Doppler pattern of diastolic filling is usually described as "restrictive" and reflects a decrease in left ventricular chamber compliance. A restrictive pattern of left ventricular filling was also identified in the subgroup of 16 study patients who had undergone optimal iron chelation therapy with deferoxamine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Coronary disease. II. Analysis of diastolic pressure-volume correlations and left ventricular elasticity in 110 patients]

Left ventricular pressure-volume relationships as well as diastolic compliance were determined in 110 patients with coronary heart disease during routine right and left heart catheterization, coronary angiography and ventriculography. 1. Enddiastolic and endystolic volume of the left ventricle were increased in severe coronary heart disease dependent on the degree of coronary stenosis; left ventricular ejection fraction was consecutively reduced. 2. Left ventricular enddiastolic pressure, diastolic pressure difference and diastolic rate of pressure rise were increased in corrleation with coronary artery stenosis. In contrast, last diastolic volume inflow into the left ventricle was nearly the same in all groups. Left ventricular stiffness, expressed as dP/dV, was significantly increased dependent on the severity degree of coronary artery disease. 3. Diastolic pressure-volume relationships revealed greater steepness in coronary artery disease, significantly dependent, on the corresponding severity degree. 4. Hemodynamic measures (stroke volume, cardiac index, ejection fraction) were decreased parallel to the increased left ventricular wall stiffness. The results demonstrated decreased left ventricular compliance in coronary heart disease. There was a striking correlation between the severity degree of coronary heart disease and the decrease of left ventricular compliance. Validity and limitations of the techniques of estimating left ventricular compliance from diastolic pressures and volumes as well as the effects of a decrease of left ventricular compliance on cardiac mechanics are discussed.     

Assessment of global and regional left ventricular diastolic function in hypertensive heart disease using automated border detection techniques

Acoustic quantification (AQ) and color kinesis (CK) are techniques that involve automated detection and tracking of endocardial borders. These methods are useful for the evaluation of global and regional left ventricular (LV) systolic function and more recently have been applied to evaluating LV diastolic performance. Assessment of diastolic dysfunction in hypertensive heart disease is a relevant clinical issue in which these techniques have proven useful. The diastolic portion of left atrium and LV AQ area waveforms are frequently abnormal in patients with left ventricular hypertrophy (LVH). Left ventricular AQ curves consistently demonstrate reduced rapid filling fraction (RFF) and peak rapid filling rate (PRFR), elevated atrial filling fraction (AFF), peak atrial filling rate (PAFR), and reductions in the ratio PRFR/PAFR. Acoustic quantification complements traditional Doppler echocardiographic evaluation of global diastolic function. Many patients with significant LVH and normal Doppler diastolic parameters can be identified as having diastolic dysfunction with AQ. In addition, CK has allowed the evaluation of regional diastolic performance in hypertensive patients. Regional filling curves obtained from CK have demonstrated that endocardial diastolic motion is commonly delayed and heterogeneous in patients with LVH.     

Tissue Doppler to Assess Diastolic Left Ventricular Function

Doppler indices of left ventricular (LV) filling have been used traditionally for the assessment of LV diastolic function. In many circumstances, however, the interpretation of these indices is difficult because they respond to alterations of different physiological variables such as preload, relaxation, and heart rate. A typical example of their limitation is seen in patients with abnormal LV relaxation and increased preload compensation, who often present a "pseudonormal" LV filling pattern. Thus, there is a need for noninvasive indices of diastolic function capable of discriminating the effects of relaxation and preload. Tissue Doppler echocardiography (TDE) is available in most modern cardiac ultrasound imaging systems. TDE can be used to obtain regional myocardial velocities during isovolumic relaxation, early filling, and atrial systole with high spatial and temporal resolution. This article discusses the complementary role, limitations, and future challenges of TDE in the study of diastolic function.     

Assessment and impact of diastolic function by echocardiography in elderly patients

Doppler echocardiography is the gold standard for assessment of diastolic dysfunction, which is increasingly recognised as a cause of heart failure, especially in the elderly. Using a combination of Doppler echocardiography techniques, it is possible to identify grades of diastolic dysfunction, estimate left ventricular filling pressures and establish the chronicity of diastolic dysfunction. These physiologically-derived measures have been widely validated against invasive measurements of left heart pressures and have been shown to be prognostically valuable in a wide range of clinical settings. This review explores the mechanisms, and approaches to the assessment of diastolic dysfunction in the elderly. The challenge for clinicians is to identify pathophysiological changes from those associated with normal ageing. When used in combination, and taking age into account, Doppler echocardiographic parameters are helpful in the assessment of dyspnoea in older patients and provide prognostic insights.     

Noninvasive assessment of left ventricular diastolic function: comparative analysis of Doppler echocardiographic and radionuclide angiographic techniques

This investigation was performed to determine whether variables obtained directly from the Doppler left ventricular diastolic flow velocity profile provide a reliable estimate of diastolic function. Measurements of diastolic flow velocity obtained by Doppler echocardiography were compared with volumetric measurements of left ventricular diastolic filling determined by radionuclide angiography in 12 subjects without cardiac disease and in 25 patients with a variety of cardiac diseases. The two methods were in agreement in distinguishing normal from abnormal diastolic function in 21 (84%) of the 25 patients with cardiac disease, identifying diastolic function as normal in 8 and abnormal in 13 of these patients. Good correlations were observed between certain Doppler variables of left ventricular diastolic flow velocity and radionuclide angiographic variables of left ventricular filling. The time interval from the aortic closing component of the second heart sound to the end of the early diastolic flow velocity peak, assessed with Doppler echocardiography, correlated well with the time interval from end-systole to the end of rapid filling, assessed with radionuclide angiography (r = 0.83). Descent of the Doppler early diastolic flow velocity peak correlated well with the radionuclide angiographic peak filling rate (r = 0.79). The ratio between the heights of the early and late (due to atrial systole) peaks of diastolic flow velocity showed good correlation with the ratio between percent of left ventricular filling during rapid filling and during atrial systole (r = 0.76). These findings demonstrate that the left ventricular diastolic flow velocity profile obtained with Doppler echocardiography compares favorably with radionuclide angiographic variables in the evaluation of left ventricular diastolic function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of Reduced Preload on Diastolic Filling in Essential Hypertensive Patients With Increased Left Ventricular Mass

Doppler-derived indices of diastolic filling are widely used in the routine evaluation of essential hypertensives. However, these indices are affected by loading conditions and systolic performance. This study aimed at monitoring the transmitral flow pattern and indices of left ventricular systolic function during acute nonpharmacological isolated reduction of preload in essential hypertensives with left ventricular hypertrophy.Nine essential hypertensive patients with left ventricular hypertrophy and nine age- and sex-matched normotensive controls underwent echocardiographic and Doppler evaluation of both systolic function and diastolic filling indices at baseline and during lower body suction at −40 mm Hg. Lower body suction caused a similar decrease in end-diastolic volume index, stroke volume index, and midwall fractional shortening in the normotensives and hypertensives. Circumferential end-systolic stress was unaffected in both groups. Acceleration time of early diastolic filling and isovolumic relaxation time increased in the normotensives but not in the hypertensives. Deceleration time of early diastolic filling increased in both groups. The ratio of peak velocities during early filling and at atrial contraction decreased in the normotensives, whereas it was unchanged in the hypertensives; this was due to the fact that early filling velocity decreased in both groups, whereas peak velocity at atrial contraction decreased only in the hypertensives.We conclude that Doppler-derived diastolic filling indices are not affected by a reduction of preload in essential hypertensives with left ventricular hypertrophy.     

Analysis of the early transmitral Doppler velocity curve: effect of primary physiologic changes and compensatory preload adjustment

Left ventricular filling (as assessed by Doppler echocardiography) has previously been shown to depend in a complex fashion on ventricular diastolic function (compliance and relaxation) as well as other variables, such as atrial pressure and compliance, ventricular systolic function and mitral valve impedance. To study the effect of isolated physiologic alterations on individual Doppler indexes, a mathematic model of mitral flow was analyzed. By varying one physiologic variable at a time, it was shown that mitral velocity acceleration is affected directly by atrial pressure and inversely by the ventricular relaxation time constant, with relatively little impact of chamber compliance. Deceleration rate was directly influenced by mitral valve area, atrial pressure and ventricular systolic dysfunction and inversely affected by atrial and ventricular compliance relations, with little impact of relaxation unless it was so delayed as to be incomplete during deceleration. Peak velocity was directly affected most strongly by initial left atrial pressure, and lowered somewhat by prolonged relaxation, low atrial and ventricular compliance and systolic dysfunction. Strikingly different filling patterns emerged when the primary physiologic alterations were accompanied by simultaneous compensatory changes in atrial pressure designed to maintain stroke volume constant. Low ventricular compliance with preload compensation produced characteristic E waves with very short acceleration and deceleration times and high peak velocity. Thus, mathematic analysis of ventricular filling helps to explain the physical and physiologic basis for the transmitral velocity curve.