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(Circulation. 1995;92:811-818.)
© 1995 American Heart Association, Inc.

Articles

Effects of Valve Surgery on Left Ventricular Contractile Function in Patients With Long-term Mitral Regurgitation

Presented at the 65th Scientific Sessions of the American Heart Association, November 1992, New Orleans, La.

Mark R. Starling, MD

From the Division of Cardiology, Department of Internal Medicine, University of Michigan (Ann Arbor) and VA Medical Centers.

	Abstract

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Background Patients with long-term mitral regurgitation were studied both before and 1 year after successful valve surgery to test the hypothesis that impaired left ventricular contractile function improves after surgery for long-term mitral regurgitation in humans.

Methods and Results Fifteen patients with long-term mitral regurgitation were studied. Micromanometer left ventricular pressures and radionuclide angiograms for left ventricular volumes were acquired over a range of loading conditions both before and 1 year after successful valve surgery for long-term mitral regurgitation. To assess both left ventricular contractility and pump efficiency, we used left ventriculoarterial coupling to evaluate the interaction of the left ventricle with the arterial system with the use of the left ventricular contractile index, E_es, and effective arterial elastance, E_a. Left ventricular pump efficiency was expressed as the ratio of forward left ventricular stroke work to the corresponding pressure–volume area. All patients had successful mitral valve surgery as manifest by no or only trivial residual mitral regurgitation on physical examination and Doppler echocardiography. The average radionuclide regurgitant index of 1.28±0.56 was also less than the preoperative value of 2.70±0.80 (P<.0001). The mean left ventricular end-diastolic volume index decreased from 137±37 to 90±31 mL/m² (P<.001), and the average left ventricular end-systolic volume index also decreased (59±29 to 45±27 mL/m², P<.01), although individual variation was observed. The average left ventricular ejection fraction fell from 0.58±0.12 to 0.53±0.16, which was not significant. In contrast, E_es increased from a mean value of 0.95±0.66 mm Hg/mL during the preoperative study to 2.62±2.16 mm Hg/mL at the 1-year postsurgical study (P<.01). This improvement in left ventricular contractility was observed in patients with long-term mitral regurgitation, who before surgery had preserved left ventricular ejection fraction (P<.001), less left ventricular dilation at end diastole (P<.01) and end systole (P<.001), and less impaired left ventricular contractility. Because effective arterial elastance was unchanged, left ventriculoarterial coupling also improved from an average of 0.47±0.39 to 1.81±1.63 (P<.01). Consequently, left ventricular pump efficiency improved from a mean preoperative value of 0.23±0.10 to 0.55±0.22 at the 1-year postsurgical study (P<.0001).

Conclusions The results indicate that left ventricular contractile impairment is reversible in many patients with long-term mitral regurgitation. In fact, these data indicate that mitral valve surgery can be recommended to preserve left ventricular contractility in patients with long-term mitral regurgitation, particularly in those patients who before surgery have normal left ventricular ejection fractions and less left ventricular dilation and contractile impairment.

Key Words: ventricles • contractility • mitral valve • regurgitation

	Introduction

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The hemodynamic course of long-term mitral regurgitation is manifest by progressive left ventricular dilation with preserved left ventricular ejection fraction until irreversible left ventricular pump dysfunction supervenes.¹ Presumably, the deterioration in left ventricular contractile state that results in irreversible pump dysfunction must also be progressive, but the preservation of left ventricular ejection fraction due to the low impedance to ejection provided by the left atrium obscures lesser degrees of contractile impairment. Recent data in patients with long-term mitral regurgitation indicate that left ventricular contractile function may be impaired, despite preservation of left ventricular ejection fraction.² Similar observations have been made in an animal model of mitral regurgitation.^{3 4} In this animal model, left ventricular contractile function is reduced, whereas left ventricular ejection fraction remains normal, after the creation of mitral regurgitation; when mitral valve replacement is performed with or without preservation of the submitral apparatus, left ventricular ejection fraction either does not change or falls, whereas left ventricular contractile impairment recovers toward normal. Whether recovery of left ventricular contractile impairment also occurs after successful valve surgery for long-term mitral regurgitation in humans is controversial.

Accordingly, patients with long-term mitral regurgitation were studied both before and 1 year after successful valve surgery to test the hypothesis that left ventricular contractile impairment improves after surgery for long-term mitral regurgitation in humans.

	Methods

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Patients
The study population consisted of 15 patients, who were referred to evaluate the hemodynamic severity of their long-term mitral regurgitation and who subsequently had successful mitral valve surgery. This included 14 men and 1 woman with an age range of 47 to 68 years (mean±SD age, 57±7 years). All of these patients had a physical examination, which was consistent with severe mitral regurgitation. They also were in normal sinus rhythm according to ECG, had left ventricular dilation on two-dimensionally targeted M-mode echocardiography with an end-diastolic dimension of 60 mm or more, and had normal coronary arteries with severe angiographic mitral regurgitation at cardiac catheterization.

Protocol
Each of these 15 patients provided written, informed consent for this investigation on forms approved by the Institutional Review Board at the University of Michigan or by the Human Studies Subcommittee of the Research and Development Committee at the Veterans Affairs Medical Center in Ann Arbor, Mich. All medications were withheld for 24 hours before cardiac catheterization. After a diagnostic right and left heart catheterization, a bipolar pacing catheter was placed in the right atrial appendage to maintain a constant heart rate, a micromanometer left ventricular pressure catheter (Millar Instruments) was positioned to measure high-fidelity aortic and left ventricular pressures, and red blood cells were tagged with ^99mTc for radionuclide angiography. Then, micromanometer left ventricular pressures and gated equilibrium radionuclide angiograms were acquired in duplicate during multiple left ventricular loading conditions produced by steady state infusions of either methoxamine or nitroprusside.

Patients, who had undergone successful mitral valve surgery for long-term mitral regurgitation documented by physical examination and two-dimensional echocardiography Doppler studies, were asked to return electively for a second study 1 year after their operation. The protocol was the same as that performed before surgery. There was no selection bias based on clinical status, concern regarding left ventricular function, or concern for prosthetic valve dysfunction or adequacy of valve repair.

Hemodynamics
The left ventricular pressure waveforms were averaged, digitized at a variable sampling frequency, and interpolated to correspond with each radionuclide frame throughout the cardiac cycle. The program developed in our laboratory for analyzing left ventricular pressure signals has been described elsewhere.^{5 6}

Radionuclide Angiography
Gated equilibrium radionuclide angiograms were acquired for 30-millisecond frames throughout the cardiac cycle for 250 cardiac cycles. During the midportion of each radionuclide acquisition, a 2-mL blood sample was drawn and later counted for 2 minutes. The time delay was recorded for decay correction. At the completion of the protocol, a distance measurement was obtained for attenuation correction. Radionuclide left ventricular volumes were calculated on a frame-by-frame basis from background-subtracted, handdrawn region-of-interest left ventricular count data that were standardized for frame duration, cardiac cycles acquired, decay-corrected blood sample counts, and attenuation.^{7 8 9}

Data Analysis
Corresponding micromanometer left ventricular pressures and radionuclide left ventricular volumes for each loading condition were plotted to obtain multiple pressure–volume loops for each patient. The maximal pressure–volume ratio from each pressure–volume loop was subjected to linear regression analysis to obtain a slope (E_es) reflecting left ventricular chamber elastance, a relatively load-independent index of left ventricular contractility.^{10 11} Because E_es has been shown to be influenced by heart size,¹² we undertook a mathematical correction of the E_es values to account for the changes in heart size, defined as left ventricular end-diastolic volume, that occurred between the two studies.¹³ Thus, left ventricular chamber elastance could be compared after adjustments for changes in heart size to determine whether left ventricular contractility had indeed been affected by the valve surgery after minimizing the confounding influence of the dependence of E_es on heart size.

Representative examples of the baseline pressure–volume loops and E_es values from a patient both before and 1 year after successful mitral valve surgery are shown in Fig 1. It is important to recognize that there were significant changes in both E_es and left ventricular end-diastolic volume. This patient example reinforces the importance of considering the effects of changes in heart size on E_es in this patient population before drawing any conclusion regarding the long-term effects of valve surgery on left ventricular contractility.

View larger version (0K): [in this window] [in a new window]   Figure 1. Examples of the baseline pressure–volume loops and end-systolic pressure–volume relations from a representative patient both before and 1 year after successful mitral valve surgery. It is important to recognize that with the change in left ventricular chamber elastance (Ees), there was a change in left ventricular end-diastolic volume that may have affected Ees. Accordingly, it is important to consider the influence of a change in heart size on Ees in this population of patients.

To obtain effective arterial elastance (E_a), we divided end-systolic pressure, defined as the pressure at the maximum pressure–volume ratio, by radionuclide left ventricular stroke volume. To obtain forward left ventricular stroke volume (SV_f) in the mitral regurgitation patients before valve surgery, total left ventricular stroke output was divided by regurgitant index to partition it into forward and regurgitant left ventricular stroke volumes. Left ventricular regurgitant index was obtained by dividing left ventricular stroke counts by right ventricular stroke counts, where right ventricular stroke counts were obtained by a modification of the method of Maddahi et al.^{14 15} Because no clinical evidence existed either by physical examination or Doppler echocardiography for residual mitral regurgitation after valve surgery, total left ventricular stroke output at 1 year was considered to be synonymous with SV_f during the initial study. Coupling of the left ventricle to the arterial system was then expressed as the ratio of E_es to E_a (E_es/E_a).

To assess left ventricular pump efficiency, we obtained left ventricular stroke work (SW) through calibrated planimetry of each pressure–volume loop. The result was multiplied by 0.0136 to convert from millimeters of mercury per milliliter to gram-meters. Left ventricular pressure–volume areas were obtained with calibrated planimetry of the area enclosed by the end-systolic and diastolic curves and the systolic portion of each pressure–volume loop.^{16 17 18} The ratio of external work to pressure–volume area is reflective of left ventricular pump efficiency, that is, the efficiency of converting the total energy available to the left ventricle into external work. To fully examine the energetics of the left ventricle in patients with long-term mitral regurgitation, a modification of the concepts of Suga et al^{16 17 18} was introduced. They characterized a two-step process whereby the conversion of myocardial oxygen consumption into the pressure–volume area, reflecting contractile efficiency, is followed by the conversion of the pressure–volume area into external work, reflecting pump efficiency. Then, the relation between myocardial oxygen consumption and external work is representative of myocardial efficiency, which can be affected by (1) the efficiency of the contractile machinery or (2) the conversion of total mechanical energy into external work, which is dependent on coupling of the left ventricle to the arterial system.¹⁹ In patients with long-term mitral regurgitation, conversion of the left ventricular pressure–volume area into external work is reflective not only of forward left ventricular stroke work (SW_f) but also of regurgitant SW. Therefore, although the left ventricle may perform total SW efficiently, this does not provide insight into the efficiency of performing SW_f, which, in the case of long-term mitral regurgitation, would be more consistent with original calculations of left ventricular pump efficiency^{16 17 18} and more reflective of the efficiency of performing physiologically meaningful work. Accordingly, to obtain SW_f in the patients with long-term mitral regurgitation before mitral valve surgery, total SW was divided by regurgitant index in an attempt to eliminate regurgitant work. Thus, left ventricular pump efficiency for performing SW_f could be characterized after regurgitant SW was eliminated, and then only SW_f was compared with the corresponding pressure–volume area.

Statistical Analysis
All values are given as the mean±1 SD. The data were analyzed with paired t tests, and a significant difference was considered present when a probability of .05 was observed.

	Results

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Hemodynamics
The hemodynamic data from the initial study and the 1-year postsurgical study are given in Table 1. The mean heart rates did not differ. Both average right atrial and pulmonary capillary wedge pressures decreased (P<.02 and P<.01, respectively). Left ventricular end-diastolic pressure also decreased (P<.01). Left ventricular peak systolic pressure increased and mean aortic pressure decreased, but neither of these changes were significant. The average cardiac index also did not change appreciably (2.81±0.70 to 2.98±1.15 L · min^-1 · m^-2).

View this table: [in this window] [in a new window]   Table 1. Hemodynamic Data

The mean left ventricular end-diastolic volume index decreased from 137±37 to 90±31 mL/m² (P<.001), as did the average left ventricular end-systolic volume index (59±29 to 45±27 mL/m², P<.01), despite significant individual variation. Consequently, the average left ventricular ejection fraction decreased from 0.58±0.12 to 0.53±0.16, whereas the mean regurgitant index decreased from 2.70±0.80 to 1.28±0.56 (P<.0001).

Left Ventricular Contractility
To assess left ventricular contractility, we calculated E_es during the initial and 1-year postsurgical studies. E_es was useful for this particular application, since we assessed changes in left ventricular chamber performance from the initial to the 1-year postsurgical study; and we corrected the E_es values for the corresponding changes in heart size.¹³ These data are given in Table 2 and Fig 2. The average E_es value was 0.95±0.66 mm Hg/mL during the initial study, and it increased to 2.62±2.16 mm Hg/mL (P<.01) during the 1-year postsurgical study. In addition, after a correction for heart size, there was also a similar increase in the corrected E_es values that remained significant (Fig 2). Thus, even after a correction for the corresponding changes in heart size, there was an increase in the E_es values in excess of what one might have expected due solely to the interval changes in left ventricular end-diastolic volume. This was also evident by the fact that the average extrapolated volume–axis intercepts, V_o, did not change significantly. Thus, a specific change in the slope of the end-systolic pressure–volume relation occurred, rather than a shift in the relation due to volume changes, consistent with the concept that left ventricular contractility improved.

View this table: [in this window] [in a new window]   Table 2. Left Ventriculoarterial Coupling

View larger version (0K): [in this window] [in a new window]   Figure 2. Left, Plot of individual and mean left ventricular chamber elastance (Ees) (Ees in figure) values. Right, Plot of individual and mean heart size–corrected Ees values. Significant differences are noted.

Two further analyses of the changes in left ventricular contractility were performed. First, patients were divided into those who underwent mitral valve repair (n=7) and those who underwent mitral valve replacement (n=8) to establish whether there were any specific differences in the response of left ventricular size, performance, and contractility related to the type of valve surgery performed. There were none identified, probably due to the few patients included in this investigation and the fact that this investigation was not designed to address this issue. Second, as is evident in Fig 2, five patients continued to have an abnormal E_es value 1 year after successful mitral valve surgery, whereas 10 patients had improvement in their E_es values into the normal range (E_es1.00 mm Hg/mL) after successful mitral valve surgery. When the preoperative hemodynamic data in these two groups of patients were compared, several differences were identified. In contrast to the patients, who improved their E_es values at the postoperative study, the patients who continued to have abnormal left ventricular contractility had a larger preoperative mean left ventricular end-diastolic volume index (173±30 versus 119±26 mL/m², P<.01) and end-systolic volume index (89±28 versus 44±12 mL/m², P<.001), a lower average left ventricular ejection fraction (0.49±0.12 versus 0.63±0.09, P<.05), and a lower mean E_es value (0.53±0.25 versus 1.16±0.71 mm Hg/mL). Thus, patients with more severe left ventricular dilation, pump dysfunction, and contractile impairment did not have an improvement in left ventricular contractility after successful mitral valve surgery, whereas those with less left ventricular dilation, normal ejection fraction, and less severe contractile impairment responded favorably to successful mitral valve surgery with an improvement in left ventricular contractility.

Left Ventriculoarterial Coupling Relations
Left ventricular end-systolic pressure, P_es, increased from 108±17 to 124±19 mm Hg (P<.05) (Table 2). SV_f also increased from 57±20 to 84±29 mL (P<.01). Thus, because SV_f increased to the same extent as P_es, effective E_a was unchanged. Because E_es increased and E_a did not change significantly, there was an improvement in left ventriculoarterial coupling (0.47±0.39 to 1.81±1.63, P<.01, Fig 3). The average SW_f increased from 61±25 to 99±46 g-m (P=.01), and the mean left ventricular pump efficiency also improved. The average left ventricular pump efficiency increased from 0.23±0.10 to 0.55±0.22 (P<.0001, Fig 3). Furthermore, 1 year after successful mitral valve surgery, the patients who did not improve their left ventricular contractility had a larger mean left ventricular end-diastolic volume index (111±29 versus 79±27 mL/m², P=.05) and end-systolic volume index (66±34 versus 34±17 mL/m², P<.05), a lower mean ejection fraction (0.43±0.19 versus 0.58±0.11), a lower mean E_es/E_a (0.43±0.27 versus 2.50±1.58, P=.01), and a worse average pump efficiency (0.33±0.17 versus 0.67±0.13, P<.001) compared with patients with long-term mitral regurgitation who improved their left ventricular contractility after mitral valve surgery.

View larger version (0K): [in this window] [in a new window]   Figure 3. Left, Plot of individual and mean left ventriculoarterial coupling ratios (Ees/Ea) (Ees/Ea in figure). Right, Plot of individual and mean left ventricular pump efficiency values for performing forward stroke work (SWf/PVA) (SWf/PVA in figure). Significant differences are noted.

To obtain a better appreciation of the changes in left ventriculoarterial coupling, we plotted left ventricular pump efficiency for performing SW_f against the left ventriculoarterial coupling ratio, E_es/E_a (Fig 4). The curvilinear relation between left ventricular pump efficiency and left ventriculoarterial coupling is shown for a control population previously reported from this laboratory.¹⁹ The pump efficiency of performing SW_f for the mitral regurgitation patients during the initial study fell on the lower left end of this continuum. Since the average E_a in the initial study was similar to that previously reported in a control population,¹⁹ this supports the concept that the reduction in pump efficiency was not due to excess arterial load in these patients and thus must result from contractile impairment. Furthermore, in the 1-year postsurgical study, there was an upward and rightward movement of individual values along this continuum toward more normal values. The improvement in left ventricular pump efficiency of performing SW was therefore due to improved left ventriculoarterial coupling resulting from the improvement in contractile function, since E_a was unaffected by successful mitral valve surgery.

View larger version (0K): [in this window] [in a new window]   Figure 4. Plot of left ventricular pump efficiency for performing forward left ventricular stroke work (SWf/PVA) (SWf/PVA in figure) on the ordinate against the corresponding left ventriculoarterial coupling ratios, Ees/Ea (Ees/Ea in figure) on the abscissa. The curvilinear relation for a previously reported control population is shown.19 Note that the pump efficiency and left ventriculoarterial coupling ratios move upward and to the right from the initial study toward more normal values at the postsurgical study.

The effects of successful valve surgery for long-term mitral regurgitation on SW_f are displayed in a different format in Fig 5. This figure shows the theoretical curve relating normalized SW to left ventriculoarterial coupling over a range of values in a control population of patients.¹⁹ On this relation, the SW_f values in the mitral regurgitation patients both before and after successful valve surgery have been standardized to the maximum value that would be expected in a control population at an E_es/E_a of 1.0. This value was chosen because it represents the maximal output that one would expect if the left ventricle and arterial system were optimally coupled.^{20 21 22} During the initial study, the patients with long-term mitral regurgitation fell on the left downslope of this relation, consistent with left ventricular contractile impairment. After successful surgical correction of long-term mitral regurgitation, these values shifted upward and to the right along the downslope seen in a control population. If the relation between normalized SW and the E_es/E_a is plotted over a range of arterial load produced by nitroprusside, the curve is similar to that established in a previously reported control population.

View larger version (0K): [in this window] [in a new window]   Figure 5. Plot of normalized forward left ventricular stroke work on the ordinate against the left ventriculoarterial coupling ratio, Ees/Ea (Ees/Ea in figure) on the abscissa. Dashed line represents the theoretic curve for a normal heart predicting the maximal stroke work at an Ees/Ea of 1.0. This is set to 100%. The normalized forward left ventricular stroke work for the long-term mitral regurgitation (MR) patients both before and 1 year after successful valve surgery is plotted against this normal curve. The normalized forward left ventricular stroke work for the MR patients fell on the left downslope before surgery and on the right downslope after successful mitral valve surgery. Examination of this later relation over a full range of arterial load produced by nitroprusside demonstrates that the relation after surgery for this group of MR patients was similar to that expected in a control population.

	Discussion

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The purpose of the present study was to determine whether impaired preoperative left ventricular contractility improves after successful valve surgery for long-term mitral regurgitation in humans. It is evident from the data that left ventricular contractile impairment, which is obscured by favorable preoperative left ventricular loading conditions,²³ improves in many, but not all, patients after successful valve surgery for long-term mitral regurgitation. The data also suggest that due to the improvement in contractility, left ventriculoarterial coupling improves, leading to enhanced left ventricular pump efficiency. It is also apparent from these data that the improvement in left ventricular contractility occurred in patients with long-term mitral regurgitation, preserved left ventricular ejection fractions, and more mild contractile impairment. It further demonstrates that patients with left ventricular pump dysfunction and more severely impaired left ventricular contractile function do not improve their contractile function. These patients with preoperative left ventricular pump dysfunction did not improve their average left ventricular ejection fraction, left ventriculoarterial coupling, or pump efficiency. These data support the conclusion that mitral valve surgery can be recommended earlier to preserve left ventricular contractility and pump efficiency in many patients with long-term mitral regurgitation.

However, not all patients with long-term mitral regurgitation and contractile impairment had an improvement in contractility or pump efficiency. Previous clinical studies, whether cineangiographic,²⁴ nuclear,²⁵ or echocardiographic,^{26 27} have focused on identifying patients with long-term mitral regurgitation, who do poorly after mitral valve surgery. Several indexes from these studies have been proposed as guidelines to help decide when to surgically intervene in patients with long-term mitral regurgitation.¹ However, it seems teleologically inappropriate to await the development of clinical indexes that suggest the long-term outcome will be poor, manifest by either persistent left ventricular dilation and dysfunction or a premature cardiac death. An examination of the data in Figs 2 and 3 illustrates that as left ventricular contractile impairment becomes severe, it may be irreversible, and thus no improvement in left ventricular contractile function or pump efficiency should be expected. These data emphasize the importance of more timely surgical intervention before irreversible contractile impairment and pump dysfunction supervenes. Pertinent to this consideration is the observation in this investigation that patients with long-term mitral regurgitation, who responded unfavorably to successful mitral valve surgery with persistent left ventricular dilation and dysfunction, had preoperative left ventricular end-systolic volume indexes that averaged 89±28 mL/m², whereas those who had a favorable contractile response had end-systolic volume indexes that averaged 44±12 mL/m². These data support the recommendation that patients with long-term mitral regurgitation should be referred for mitral valve surgery earlier, when their end-systolic volume indexes are in the range of 40 to 50 mL/m² and not more than 60 mL/m², which is when a poor outcome might be more consistently expected.²⁸ Moreover, on the basis of these data, this recommendation would not subject patients with long-term mitral regurgitation to a premature surgical procedure.

It seems inappropriate to assume that contractile function would not undergo a progressive deterioration toward irreversible contractile impairment. A recent clinical study tested the hypothesis that left ventricular contractile function progressively deteriorates in patients with long-term mitral regurgitation and that, if successful mitral valve surgery was performed in a timely fashion, left ventricular ejection fraction could be preserved.² This investigation identified patients with mild left ventricular contractile impairment who, soon after mitral valve surgery, had significant reductions in left ventricular size and ejection fraction, but on long-term follow-up, they demonstrated recovery of left ventricular ejection fraction to within the normal range. This recovery occurred to such an extent that left ventricular size and ejection fraction 1 year after mitral valve surgery were comparable to those in patients with preoperative normal left ventricular contractile function. Several possible explanations for these observations include improved preload, reduced afterload, or recovery of contractile function. It is evident from this investigation that an improvement in contractile function may play a prominent role in the late recovery of left ventricular ejection fraction in some patients with long-term mitral regurgitation and less preoperative impairment of left ventricular contractility.

The data in this investigation that left ventricular contractility improves after valve surgery for long-term mitral regurgitation are supported by data from an animal model of mitral regurgitation.^{3 29} Nakano et al³ have shown in an animal model of mitral regurgitation that several indexes of left ventricular contractility deteriorate after the creation of mitral regurgitation, whereas left ventricular ejection fraction is maintained. Of importance is that the reduction in left ventricular contractility observed in these animals is reversible with correction of the valve lesion. A possible mechanism for this progressive but reversible decrease in left ventricular contractility appears to be related, at least in part, to ß-receptor downregulation.³⁰ Evidence that ß-receptor downregulation may play an important role in the progressive deterioration in left ventricular contractility in this model of mitral regurgitation is provided from animals in which left ventricular contractile impairment was improved with ß-adrenergic blocking therapy.³⁰ Pathological data have also demonstrated a decrease in myocyte myofibrillar protein content in these animals.³¹ With surgical correction of the valve lesion, these pathological abnormalities are also reversed. Thus, this animal model of mitral regurgitation provides additional documentation for the deterioration in contractile function that was previously demonstrated in patients with long-term mitral regurgitation.² It is also supportive of the observation in this investigation that left ventricular contractile impairment is potentially reversible in many patients if valve surgery for long-term mitral regurgitation is performed in a timely fashion.

A final observation is warranted regarding the assessment of left ventricular pump performance in patients with long-term mitral regurgitation. In this investigation and in animal studies of mitral regurgitation,^{3 4} a decrease in left ventricular ejection fraction was observed, despite significant improvement in left ventricular contractility, after mitral valve surgery. The increase in left ventricular contractility in many of the patients studied in the present study was the major reason for the improvement in left ventricular pump efficiency. This was manifest by improvement in left ventriculoarterial coupling and the efficiency of energy transfer from the left ventricle to the arterial system. These data indicate that despite variable changes in left ventricular ejection fraction, left ventricular pump efficiency can substantially improve in the majority of these patients, if surgical intervention occurs in a timely fashion.

It is also important to note that left ventricular pump efficiency, defined as the ratio of total left ventricular stroke work to the pressure–volume area, is maintained in patients with long-term mitral regurgitation, but the pump efficiency for performing SW_f is severely impaired in these patients. The original concept proposed by Suga et al^{16 17 18} suggests a two-step process whereby myocardial oxygen consumption is transferred to the pressure–volume area and the total energy in the pressure–volume area is then partially converted into external work depending on left ventriculoarterial coupling. Although these two steps are inherently operative in most patient populations, a third step must be proposed in patients with long-term mitral regurgitation. Total SW must be divided into SW_f, which reflects effective forward work for tissue perfusion and the ineffective work of volume regurgitation into the low-impedance left atrium. In contrast to all other patient populations, patients with long-term mitral regurgitation do SW_f inefficiently, whereas total SW is done efficiently due to the low energy cost of regurgitant work done into the low-impedance left atrium. With the addition of this third step, left ventricular pump efficiency in patients with long-term mitral regurgitation conventionally defined is severely impaired despite the outward appearance of a normal left ventricular ejection fraction. Therefore, these data also suggest that an earlier consideration of mitral valve surgery is warranted when impaired left ventricular contractility may be reversible and left ventricular pump efficiency for performing SW_f can be improved.

One potential limitation to this investigation is the use of left ventricular chamber elastance to detect a change in left ventricular contractility in patients with left ventricular volume overload. Left ventricular chamber elastance is influenced by heart size.¹² Accordingly, to establish whether a change in E_es is reflective of a change in contractility and not heart size, a correction for heart size is necessary. Several approaches have been proposed.^{12 13 32 33} Although there is no universally accepted method to perform this correction of E_es, we used heart size as measured by left ventricular end-diastolic volume,¹³ which may actually overcorrect for the effects of a change in heart size on E_es. There are two important factors in this investigation that would suggest the observations made using this relatively load-independent index of left ventricular contractility are appropriate. First, this index was applied in the same patients at two different time points and thus intrapatient comparisons of the changes in left ventricular contractility were important in this investigation rather than the absolute values of E_es. Second, because there were changes in heart size, each E_es value was adjusted to account for the corresponding change in heart size. We have previously used an adjustment for heart size and demonstrated that the effect of heart size on the absolute value of E_es is no more than 10% to 15%.¹³ We performed this heart size correction of E_es in this investigation, and there was no significant change in the data. This would suggest that the change in heart size observed between the two studies in this investigation did not artificially improve the left ventricular chamber elastance calculations. Therefore, it seems reasonable to conclude that a significant increase in left ventricular contractility occurred.

In conclusion, left ventricular contractile impairment is not irreversible in all patients with long-term mitral regurgitation. In fact, left ventricular contractility improves in many patients undergoing successful valve surgery for this valve lesion and, as a consequence, both left ventriculoarterial coupling and pump efficiency improve. Impaired left ventricular contractility and pump efficiency can improve, however, only if mitral valve surgery is undertaken before the development of left ventricular dilation and pump dysfunction, when left ventricular contractile impairment appears to be irreversible. Accordingly, the clinical implication of these data is that many patients with long-term mitral regurgitation are developing left ventricular contractile impairment and a reduction in forward pump efficiency despite the outward preservation of a normal left ventricular ejection fraction due to the favorable alterations in loading conditions and uncoupling of end systole from end ejection.³⁴ Mitral valve surgery should, therefore, be considered earlier in patients with less severe left ventricular dilation (end-systolic volume indexes of 40 to 50 mL/m²) and normal pump performance (left ventricular ejection fractions of 0.60 to 0.69³⁵ ) to preserve left ventricular contractility and improve pump efficiency. The specific mechanism(s) for this contractile impairment in these patients has not been fully elucidated, and further investigation into this issue is certainly warranted.

View this table: [in this window] [in a new window]   Table 1A. (Continued)

View this table: [in this window] [in a new window]   Table 2A. (Continued)

	Acknowledgments

 
This work was supported by National Institutes of Health (NIH) grant RO1-HL-36450 from the National Heart, Lung, and Blood Institute, Bethesda, Md; by Department of Veterans Affairs, Washington, DC; and by the Kughn Clinical Research Center (grant MO1-RR00042), NIH, Bethesda, Md. The assistance of Daniel Montgomery, BS, Kerri Breismeister, BS, Janet Petrusha, RN, and Penny Weaver in the preparation of this manuscript is appreciated.

	Footnotes

 
Reprint requests to Mark R. Starling, MD, Professor of Medicine, Department of Internal Medicine, Division of Cardiology, VA Medical Center, 2215 Fuller Rd, Ann Arbor, MI 48105.

Received June 8, 1994; revision received January 23, 1995; accepted February 8, 1995.

	References

Top Abstract Introduction Methods Results Discussion References

 

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