(Circulation. 1997;95:1222-1230.)
© 1997 American Heart Association, Inc.
Articles |
Loading Manipulations Improve the Prognostic Value of Doppler Evaluation of Mitral Flow in Patients With Chronic Heart Failure
the Salvatore Maugeri Foundation, IRCCS, Montescano Medical Center, Montescano, Pavia, and NOUSTAT s.r.l. (M.S.), Milan, Italy.
Correspondence to Massimo Pozzoli, MD, Department of Cardiology, Montescano Medical Center, Montescano, Pavia, Italy.
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Background Mitral flow velocity patterns (MFVPs) evaluated by Doppler echocardiography are strong predictors of survival in various cardiac diseases. However, MFVPs may change over time according to loading conditions. We performed this prospective study to assess whether changes in MFVP induced by loading manipulations provided additional prognostic information in 173 patients with chronic heart failure.
Methods and Results Simultaneous Doppler echocardiographic and right-sided hemodynamic recordings were obtained at baseline in all patients, during nitroprusside infusion in the 98 patients who had a baseline restrictive (early-to-late flow velocity ratio >1 and deceleration time 
130 ms) MFVP, and during passive leg lifting in the 75 patients who had a baseline nonrestrictive MFVP. Patients were categorized, according to changes in MFVP, into four groups: 61 patients with an irreversible restrictive, 37 with a reversible restrictive, 48 patients with a stable nonrestrictive, and 27 patients with an unstable nonrestrictive MFVP. Fifty patients experienced major cardiac events. Cox analysis revealed that MFVP was a strong predictor of events and that the response to loading manipulations improved its prognostic value. Patients with an irreversible restrictive MFVP had a higher event rate (51%) than patients with a reversible restrictive MFVP (19%). Among patients with a baseline nonrestrictive MFVP, those with a stable nonrestrictive MFVP had the lowest event rate (6%), whereas the event rate was 33% in patients with an unstable nonrestrictive MFVP.
Conclusions In patients with chronic heart failure, MFVPs provide independent prognostic information. Their prognostic value can be further increased by assessment of the changes induced in them by loading manipulations.
Key Words: heart failure • prognosis • diastole
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The assumption that all patients with congestive heart failure automatically have a poor short-term survival has been invalidated by recent studies demonstrating that a significant proportion of patients may have a relatively favorable midterm outcome on optimized medical therapy.1 2 3 Identification of subgroups of patients at different risks has important implications for deciding interventional strategies and for appropriate selection of patients for clinical trials.
Recent studies have shown that MFVP evaluated by Doppler echocardiography is a strong predictor of survival in various cardiac conditions.4 5 6 7 In particular, the so-called "restrictive" MFVP, characterized by a predominantly early diastolic flow velocity followed by a short deceleration and a reduced atrial contribution, has been recognized as an ominous prognostic sign. However, in patients with chronic heart failure, the relative prognostic value of MFVP compared with that of more established markers has not been thoroughly investigated. In addition, MFVP is a dynamic phenomenon that may change rapidly within the same patient,8 and this may limit the prognostic value of a single baseline Doppler evaluation. It has been shown that loading manipulations may induce dramatic variations in MFVPs, but the response may vary greatly between patients.9 10 11 12 Whether the assessment of such changes can improve the prognostic contribution of mitral flow variables has not yet been established.
Accordingly, the first purpose of this study was to evaluate the prognostic value of Doppler evaluation of mitral flow in a relatively large population of patients with chronic congestive heart failure who were prospectively enrolled and underwent a thorough clinical, hemodynamic, and ergometric evaluation and a close follow-up. Second, this study aimed to assess whether changes in MFVP produced by acute loading manipulations could provide additional prognostic information.
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Study Population
The study population comprised 180 consecutive patients with chronic congestive heart failure admitted to our Heart Failure Unit between August 1992 and March 1994 with a view to selection for heart transplantation. All patients fulfilled the following inclusion criteria: (1) at least two episodes of overt heart decompensation in the 6 months before the admission, (2) dilated cardiomyopathy defined by the echocardiographic demonstration of a dilated left ventricle (end-diastolic volume normalized for body surface area >78 mL/m2) with impaired systolic function (ejection fraction <35%), (3) sinus rhythm, (4) absence of unstable angina and of severe primary diseases of other organs, and (5) technically adequate Doppler and two-dimensional echocardiograms.
Study Protocol
After admission, therapy was adjusted to obtain a stable clinical condition defined by stable body weight and fluid balance and no signs of peripheral or pulmonary congestion. All patients received diuretics at flexible dosages, and all but 11, who could not tolerate ACE inhibitors, received captopril. One hundred sixty-eight patients were receiving digitalis, 44 amiodarone, 17 ß-blockers, 99 oral nitrates, and 9 hydralazine. The time needed to obtain clinical stabilization was 12±7 days (range, 6 to 76 days). Six patients who could not be weaned from infusion of inotropic and/or vasodilator agents and 1 who died before being evaluated were withdrawn from the study, leaving a final study group of 173 patients whose principal characteristics are reported in Table 1
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Clinical, Biochemical, Holter, and Functional Evaluation
After stabilization, all patients underwent a reevaluation of their clinical status. This included a complete physical examination and assessment of functional capacity according to the NYHA classification. Venous blood was collected for measurements of serum electrolytes, creatinine, and bilirubin. Plasma norepinephrine was also determined in 138 patients by high-performance liquid chromatography. A 24-hour Holter monitoring was performed in all patients. Maximal effort tolerance was quantified by the measurement of peak oxygen consumption (average values of the final 30 seconds of exercise) during a symptom-limited treadmill exercise test. Expiratory gases were analyzed by a Medical Graph System 2001 analyzer.
Hemodynamic and Doppler Echocardiographic Evaluation
To minimize incidental changes of loading conditions (and of MFVPs), which can occasionally be observed during the course of the day in patients with chronic heart failure, right-sided heart catheterization and ultrasound evaluation were carried out simultaneously, early in the morning, with the patients in the fasting state and before they had taken their morning medications.
Right-sided heart catheterization was performed with a 7F Swan-Ganz balloon-tipped catheter inserted into the right internal jugular vein and advanced through the right heart into the pulmonary artery. Baseline hemodynamic measurements, including pulmonary artery pressure, mean PAWP, and mean right atrial pressure, were made with the patients in a supine position by use of a Hewlett Packard transducer connected with a 7005 Marquette polygraph and recorded at a speed of 50 mm/s on a scale calibrated from 0 to 50 mm Hg. Cardiac output was measured by the thermodilution method as the mean of three consecutive measurements not varying by >10%. Arterial blood pressure was measured noninvasively by a calibrated semiautomatic cuff connected to the Marquette monitor. Both pulmonary and systemic arterial resistances were then calculated according to standard formulas.
A Hewlett Packard 1000 ultrasound system with 2.5- and 3.5-MHz probes was used to perform Doppler and two-dimensional echocardiographic examinations, which were obtained with the patients lying in a supine or slightly left lateral decubitus position. Examinations were recorded on a super-VHS videotape and analyzed, with the software operating in the ultrasound system, by an experienced cardiologist unaware of the hemodynamic results. Left ventricular volumes and ejection fractions were assessed by two-dimensional apical two- and four-chamber views with the modified Simpson's rule. Mitral flow velocity was assessed by pulsed-wave Doppler echocardiography from the apical four-chamber view with the sample volume positioned adjacent to the tips of the mitral leaflets in diastole. Doppler tracings were recorded at a sweep velocity of 100 mm/s, and the following measurements were averaged from five consecutive cycles: maximal early diastolic velocity, maximal late diastolic velocity, their ratio, the deceleration time of early diastolic velocity, and the left ventricular isovolumic relaxation time. Peak velocities were measured at the highest point of the spectrum. The deceleration time was measured as the interval between the peak early diastolic velocity and the point at which the steepest deceleration slope was extrapolated to the zero line. The left ventricular isovolumic relaxation time was measured as the interval between the aortic closure click and the beginning of transmitral flow. Mitral regurgitation was diagnosed and semiquantitatively graded by color flow Doppler echocardiography as previously described.13 Data on reproducibility of Doppler variables in chronic heart failure patients were recently published by our group.8 Based on Doppler measurements, two principal MFVPs were defined: (1) the restrictive MFVP characterized by an early-to-late peak velocity ratio >1 and a deceleration time 130 ms and (2) the nonrestrictive MFVP characterized by either an early-to-late peak diastolic velocity ratio <1 (whatever the value of the deceleration time) or >1 with a deceleration time >130 ms. In this population, these cutoff values best separated patients with and without markedly elevated left ventricular filling pressures (>18 mm Hg). In 13 patients, mitral flow velocity showed only a single peak with a short filling time (the so-called "summation" MFVP). This MFVP was associated with sinus tachycardia and/or first-degree AV block in all cases, and it was considered to be restrictive when the isovolumic relaxation time was <60 ms (10 patients) and nonrestrictive when it was 
60 ms (3 patients).
After completion of baseline measurements, patients with a restrictive MFVP underwent an NTP test performed as follows: NTP was infused at an initial dose of 0.5 µg/kg body wt. When hemodynamic measurements reached steady state (usually in about 5 minutes), the dose was increased by 0.5 µg·kg-1·min-1 up to a maximum of 4 µg·kg-1·min-1. The test was ended when either the maximum dose had been reached or the patients developed hypotension (systolic blood pressure <85 mm Hg), bradycardia (heart rate <50 bpm), or a drop of PAWP to <12 mm Hg. In patients who had a nonrestrictive MFVP at baseline, measurements were repeated during a passive LL maneuver (legs elevated at 45° from the horizontal position) after hemodynamic conditions had been stable for at least 3 minutes. MFVPs after interventions were defined according to the same criteria as at baseline.
Follow-up
On the basis of the hemodynamic results, therapy was further refined: when PAWP was >18 mm Hg, unloading treatment was intensified, and when it was <8 mm Hg, diuretics were reduced. Patients were then discharged from the hospital.
Of the 173 study patients, 72 were entered into the waiting list of the Northern Italy Heart Transplant project, 15 were not included in the list because of major contraindications, and 86 were considered "too well" to receive a transplant. In all cases, patients were enrolled in our Heart Failure Project and were followed up by serial evaluations performed every 6 months in our center. Between these intervals, telephone contact with patients themselves, next of kin, referral physicians, and peripheral hospitals was used to verify the patients' status.
Cardiac death and urgent heart transplantation were considered major cardiac events. Cardiac deaths were classified as follows: (1) sudden, when they occurred within 1 hour after changes in symptoms, and (2) progressive heart failure, when hemodynamic deterioration, either spontaneous or determined by precipitating factors, resulted in pulmonary edema, cardiogenic shock, or multiple organ failure. Nonfatal complications, such as hemodynamic decompensation, sustained arrhythmias, infections, and peripheral ischemic events, were considered minor events when they required hospitalization. Patients who died of noncardiac causes and those who underwent an elective heart transplantation were removed from the analysis on the date of the event.
Statistical Analysis
Descriptive data are given as mean±SD. First, to evaluate the independent association with survival (free from urgent heart transplantation) of Doppler and two-dimensional echocardiographic, clinical, biochemical, ergometric, and hemodynamic indices, Cox proportional hazards models were constructed. The model was obtained though a model-building strategy based on the best subset selection technique, followed by a detailed comparison of the most interesting models. The variables included in the analysis are listed in Table 2. Doppler indices were entered both as continuous variables and after categorization into restrictive and nonrestrictive MFVPs as defined above. Besides Doppler variables obtained at baseline, those measured after loading manipulations (either NTP infusion or LL maneuver, depending on the baseline MFVP) were entered into the analysis. In addition, the potential effects of changes in deceleration time in response to either NTP or LL were assessed by construction of two dummy variables, subtracting the values obtained at baseline from those obtained during the tests. These two dummies were not considered separately but rather were entered as a single variable into the model. Subsequently, the subjects were classified into four groups according to the MFVP at baseline and to its response during acute interventions: patients with an irreversible restrictive MFVP (restrictive MFVP at baseline that remained restrictive after NTP infusion), patients with a reversible restrictive MFVP (restrictive MFVP at baseline that reverted into a nonrestrictive MFVP after NTP infusion), patients with a stable nonrestrictive MFVP ( nonrestrictive MFVP at baseline that remained so after passive LL), and patients with an unstable nonrestrictive MFVP (nonrestrictive MFVP at baseline that became restrictive after passive LL) (Figs 1 and 2). The characteristics of the groups were compared by the Kruskal-Wallis test for continuous variables and by Fisher's exact test for categorical variables. Wilcoxon's test of the ranks of the differences was used to compare paired measurements within groups before and after interventions. Finally, a Cox regression model was used to characterize survival in the groups defined above. The four groups were introduced into the model as three indicator variables (0/1). The reference group (that with all dummies set at 0) was the stable nonrestrictive, considered to be the group with least risk. Each other group was represented by setting the corresponding indicator variable to 1. Survival was estimated by the product-limit Kaplan-Meier method, and the comparison between groups was carried out by the log-rank test. Statistical analyses were carried out with the SAS system.14
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Doppler and Hemodynamic Characteristics at Baseline and in Response to NTP and LL
At baseline, 98 patients had a restrictive and 75 a nonrestrictive MFVP. Patients with a restrictive MFVP had a worse functional status and more compromised hemodynamics (Table 1
). NTP was infused in the patients who had a baseline restrictive MFVP, and the LL maneuver was performed in the patients with a baseline nonrestrictive MFVP. Both tests were carried out without relevant complications. NTP-induced hypotension and/or bradycardia (67 patients) disappeared in all cases after the infusion was stopped.
In 61 of the 98 patients undergoing NTP infusion, MFVP remained restrictive, whereas it reverted to a nonrestrictive MFVP in the remaining 37 (Fig 3). Patients with a persistent restrictive MFVP had slightly more compromised hemodynamics at baseline, but there was a great overlap of values between the two groups (Table 3). Demographic variables, functional status, and biochemical and echocardiographic values were similar in the two subgroups, and maximal doses of NTP were not different (1.5±0.6 and 1.7±1 µg·kg-1·min-1 in patients with irreversible restrictive and reversible restrictive MFVPs, respectively). After NTP infusion, hemodynamics improved significantly in both subgroups. However, in patients with a reversible restrictive MFVP, the development of a nonrestrictive MFVP was accompanied by a consistent decrease in PAWP, which in all cases dropped to <18 mm Hg. Conversely, PAWP remained elevated in patients with a persistent restrictive MFVP, being >18 mm Hg in all but 2 patients (Fig 4 and Table 3).
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The 75 patients who had a baseline nonrestrictive MFVP and who underwent an LL maneuver were similar to patients with a baseline restrictive MFVP in terms of demographic variables, therapy, and degree of left ventricular systolic dysfunction. They were less symptomatic, however, and had a much lower PAWP (Table 1). After the LL maneuver, the MFVP remained stably nonrestrictive in 48 patients, whereas in 27 it became restrictive. As shown in Table 4, in both subgroups, the maneuver produced a significant increase in left ventricular end-diastolic volume, whereas the systolic volume remained unchanged. This led to a significant increase in cardiac index and left ventricular ejection fraction. However, in patients who developed a restrictive MFVP, there was a much greater increase in PAWP than in patients with a stable nonrestrictive MFVP (Fig 4).
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Outcome
During a follow-up of 17±9 months, major cardiac events occurred in 50 patients: 41 died (16 of sudden death and 25 of pump failure), and 9 underwent urgent transplantation. Sixty-nine patients, after discharge, experienced at least one nonfatal cardiac event requiring hospitalization. Sixteen patients underwent elective transplantation, and 2 died of noncardiac causes. Variables correlated with prognosis on univariate analysis are listed in Table 2. MFVP as assessed at baseline had a strong predictive power, and when assessed after loading manipulations, its predictive value was even stronger. Cox proportional hazards analysis, including variables obtained at baseline, led to a model that retained NYHA functional class evaluated both at admission and after stabilization, serum sodium, MFVP, and mitral regurgitant jet area as independent predictors of major cardiac events (Table 5A). When Doppler variables obtained after loading manipulations were entered into the analysis, the baseline MFVP lost its independent predictive value, whereas the MFVP observed after loading manipulations provided strong independent prognostic information (Table 5B). Invasive hemodynamic variables did not add any independent information.
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Fig 3 shows the distribution of events in patients subdivided according to the MFVP at baseline and after loading manipulations. Thirty-eight (76%) of the 50 major cardiac events occurred in the 98 patients who had a restrictive MFVP at baseline. Most events,31 however, occurred in the subgroup of patients with an irreversible restrictive MFVP, the event rate being 51%, whereas in patients with a reversible restrictive MFVP, the event rate was 19%. Among patients with a nonrestrictive MFVP at baseline, those with a stable nonrestrictive MFVP had an event rate of 6%, and those with an unstable nonrestrictive MFVP after LL, 33%. The relative risks of major events in the subgroups compared with patients with a stable nonrestrictive MFVP considered as the reference group and assessed by a Cox regression model are reported in Table 6. Kaplan-Meier survival curves are shown in Fig 5.
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Relation Between Acute Changes and Midterm Evolution of MFVP
In the 105 patients who survived, did not receive transplants, and remained in sinus rhythm, simultaneous hemodynamic and Doppler echocardiographic studies were repeated after 6 months. The MFVP remained unchanged in 89% of patients who had had either an irreversible restrictive or a stable nonrestrictive MFVP during acute loading manipulations. In contrast, 46% of patients with a reversible restrictive MFVP during NTP infusion developed a nonrestrictive MFVP after chronic therapy, and 33% of those with an unstable nonrestrictive MFVP during LL developed a restrictive one (Fig 6). In patients who had an irreversible restrictive MFVP, PAWP after 6 months was higher than in those who had a reversible restrictive MFVP (26±5 versus 19±8 mm Hg, P=.05) during acute interventions. At the 6-month evaluation, differences between PAWPs in patients with a stable or unstable nonrestrictive MFVP were not significant (11±8 versus 15±10 mm Hg).
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Discussion |
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The prognostic value of Doppler echocardiography of mitral flow in various cardiac conditions has been proved.4 5 6 7 Information concerning patients with chronic and advanced heart failure, however, is fairly limited, and the relative importance of MFVPs and of other more established indices still needs to be determined. In addition, in all previous studies, MFVP was assessed only once, at baseline, and this may be a limitation because MFVPs in some patients may "spontaneously" change (while remaining remarkably constant in others).8 In addition, MFVP may change within the same patient because of variations in loading conditions induced by either drug interventions or postural changes, but the response may vary greatly from patient to patient.9 10 11 12 Accordingly, we hypothesized that, in patients with chronic heart failure, MFVP changes in response to loading manipulations could provide an estimate of cardiovascular reserve and add incremental prognostic information.
The results of this study show that MFVPs add strong independent prognostic information to a comprehensive clinical, ergometric, and hemodynamic evaluation of patients with chronic heart failure. This is in line with a previous report specifically investigating the prognostic significance of MFVP in a similar population.5 In that report, however, ergometric and hemodynamic variables were not considered and measurements were taken only at baseline. More importantly, our results clearly demonstrate that the responses to NTP and to LL allow the identification of subgroups of patients who have markedly different prognoses despite similar baseline MFVPs. Specifically, we found that, at one extreme of the spectrum, patients with an irreversibly restrictive MFVP had almost a 40% 1-year probability of dying (or having urgent heart transplantation), whereas at the other extreme, those with a stable nonrestrictive MFVP had a <5% 1-year probability of dying. In the middle, patients in whom a restrictive MFVP at baseline reverted into a nonrestrictive one during NTP and those in whom a baseline nonrestrictive MFVP turned into a restrictive MFVP during passive LL had an intermediate risk of cardiac events. Within the two groups of patients who had changeable MFVPs during loading manipulations, patients with an unstable nonrestrictive MFVP tended to have a worse prognosis than those with a reversible restrictive MFVP. The difference in major events, however, was not significant, and a larger number of patients would be needed to confirm the relevance of these differences.
Besides being predictive of events during follow-up, changes of MFVP induced by acute loading manipulations were related to the midterm hemodynamic evolution. In fact, hemodynamic and Doppler echocardiographic measurements repeated after 6 months of optimized medical therapy usually remained constant in patients whose MFVP did not change after acute interventions, whereas the midterm evolution of left ventricular filling was remarkably variable in patients who had a reversible restrictive or an unstable nonrestrictive MFVP.
Previous studies have clarified the mechanisms that determine the restrictive MFVP, showing that it results primarily from elevated atrial driving pressures across the mitral valve and from a rapid rise of left ventricular diastolic pressure at the end of early diastole due to high left ventricular stiffness.15 16 17 In line with this interpretation, our results show that patients with a restrictive MFVP had a much higher PAWP than patients with a nonrestrictive MFVP, despite similar left ventricular volumes. In this group of patients, we administered NTP, a well known preload- and afterload-reducing agent whose effect is to transfer blood volume from the heart and the pulmonary vessels to the systemic circulation by increasing cardiac output, reducing AV valve regurgitations, and decreasing filling pressures. A few studies have previously investigated the effects of NTP on mitral flow velocity in small series of subjects with advanced heart failure.18 19 20 All concordantly found that NTP prolonged the early diastolic deceleration phase and increased the atrial contribution to filling. This beneficial effect has been attributed to the reduction of left ventricular volumes and pressures (leftward shift of the pressure/area curve) and to the improvement of left ventricular distensibility (downward shift of pressure/area curve), the latter probably being caused by the release of external constraint to left ventricular distension.
The results we obtained in the entire group of patients are consistent with these findings. In fact, cardiac output increased and both left and right filling pressures decreased by 
30%, whereas the early diastolic deceleration time of mitral flow was prolonged, the early diastolic velocity decreased, and the atrial contribution to filling increased. In this large group of patients, however, we observed a considerable variability in the individual responses to NTP despite the similar baseline clinical and hemodynamic conditions, the almost identical pretest drug regimens, and the equivalent doses of NTP administered. In fact, some patients showed a dramatic shift of left ventricular filling toward end diastole and a marked prolongation of the early diastolic deceleration phase, whereas other patients showed only modest changes in Doppler variables despite maximal doses of NTP.
It is uncertain whether this partial NTP refractoriness was due to a less pronounced vasodilatation (and therefore a smaller peripheral pooling effect) or to a more severe cardiac dysfunction, not apparent at baseline, that was unmasked by NTP. The former mechanism appears unlikely to have played a major role, because systemic vascular resistance decreased by 30% in both groups and the mean values measured after NTP were not significantly different. Right heart catheterization revealed that changes in MFVP were strongly associated with changes in PAWP. Thus, when the MFVP was persistently restrictive, PAWPs remained elevated, whereas PAWPs decreased to <18 mm Hg when the MFVP became nonrestrictive. In contrast, changes in cardiac output, left ventricular volume, and severity of mitral regurgitation after NTP were similar in the two groups. These observations, all together, support the idea that differences in intrinsic left ventricular diastolic properties may have played a major role in determining the divergent responses to NTP.
This observation is in line with that previously reported by Stevenson et al,3 who found that an intensive unloading treatment (intravenous NTP followed by oral vasodilators and diuretics) could reduce elevated PAWPs (to <16 mm Hg) without compromising cardiac output or determining hypotension in a significant proportion of patients with advanced heart failure, whereas in some other patients who had a similar baseline hemodynamic compromise, this result could not be achieved. As in our study, these different responses to unloading treatment identified subgroups of patients with different 1-year survivals (83% in patients achieving a low PAWP and 38% in those with persistently high filling pressures). In Stevenson's study, however, these results were reached by use of prolonged and invasive hemodynamic monitoring, whereas our study demonstrates that similar information can be obtained noninvasively by assessing the acute response of MFVP to NTP infusion.
Whereas among patients with a baseline restrictive MFVP (and elevated left ventricular filling pressures) an unloading intervention could differentiate subgroups with different prognoses, among those who had a baseline nonrestrictive MFVP (and low filling pressures) a similar result was obtained by a preload-increasing intervention. Unlike NTP, LL should displace blood volume from the periphery to the pulmonary circulation and the heart. Although the hemodynamic relevance of this maneuver has been challenged,21 22 our results showed that LL did indeed increase left ventricular end-diastolic volume and cardiac output. However, changes in MFVP (and in PAWP) varied between patients. In some patients, the MFVP remained steadily nonrestrictive and the increase in left ventricular end-diastolic volume was accompanied by a modest increase in filling pressures. In contrast, other patients developed a restrictive MFVP, and an end-diastolic volume increase of similar extent was attained at the expense of a far greater rise in filling pressures. These observations suggest that, once again, different degrees of diastolic dysfunction and of preload reserve may account for the divergent responses of MFVP to LL.
The mechanisms through which MFVPs (and their changes after acute interventions) are related to the progression of heart failure and prognosis are a matter for speculation. It can be hypothesized that the spectrum of MFVP responses to acute interventions is related to the extent of fibrosis and the consequent severity of diastolic dysfunction. Thus, extensive fibrosis may result in a restrictive left ventricular filling MFVP (and elevated filling pressures) refractory to acute unloading interventions. It seems logical to postulate that, under these circumstances, even chronic unloading therapy would be of limited efficacy and that several factors, including chronically elevated left ventricular wall tension, reduced coronary artery diastolic flow, increased right ventricular afterload, and AV valve regurgitation, may lead to a progressive hemodynamic deterioration and to a fatal pump failure (which indeed was the most frequent cause of death in our population).23 24 In addition, neurohormonal stimulation and excessive ventricular loading may predispose to arrhythmic deaths in these patients.25 These detrimental factors were probably less relevant (and/or the therapy more effective) in patients with "changeable" MFVPs and, even more so, in those with a stable nonrestrictive one. The results of the hemodynamic and Doppler evaluation performed after 6 months provide some support for this interpretation, but further investigations will be necessary to clarify these issues.
Conclusions
This study investigates patients with chronic heart failure due to either ischemic or nonischemic dilated cardiomyopathy, and our results cannot be generalized to other patients with less compromised left ventricular function or different cardiac diseases. This condition, however, is increasingly frequent and is leading to a growing number of patients waiting for heart transplantation. It has recently been recognized that in patients with chronic heart failure, clinical evolution and prognosis are highly variable, and even patients selected for heart transplantation may experience hemodynamic improvement and relatively long survival on optimized medical therapy.1 2 3 For these reasons, the search for accurate predictors of survival is important for deciding therapeutic strategies, including suitability and timing of heart transplantation. This study shows that MFVPs, in the context of other invasive and noninvasive prognostic indices, provide a strong independent contribution to the assessment of the risk. In addition, the prognostic value of MFVPs can be further increased by assessment of changes in them induced by NTP infusion and passive LL maneuver. We believe that Doppler echocardiography of mitral flow in conjunction with loading manipulations is a valid, rapid, and relatively simple noninvasive means for improving prognostic stratification of patients with chronic heart failure and for improving heart transplant candidate selection.
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Presented in part at the 45th Annual Meeting Scientific Session of the American College of Cardiology, Orlando, Fla, March 24-27, 1996.
Received June 18, 1996; revision received October 7, 1996; accepted October 23, 1996.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
-
Stevenson LW, Tillisch JH. Maintenance of cardiac output with normal filling pressures with dilated heart failure. Circulation. 1986;74:1303-1308.
[Abstract/Free Full Text]
-
Stevenson LW, Dracup KA, Tillisch JH. Efficacy of medical therapy tailored for severe congestive heart failure in patients transferred for urgent cardiac transplantation. Am J Cardiol. 1989;63:461-464.[Medline]
[Order article via Infotrieve]
-
Stevenson LW, Tillisch JH, Hamilton M, Luu M, Chelimsky-Fallick C, Moriguchi J, Kobashigawa J, Walden J. Importance of hemodynamic response to therapy in predicting survival with ejection fraction less than or equal to 20% secondary to ischemic or nonischemic dilated cardiomyopathy. Am J Cardiol. 1990;66:1348-1354.[Medline]
[Order article via Infotrieve]
-
Pinamonti B, Di Lenarda A, Sinagra GF, Camerini F, and the Heart Muscle Disease Study Group: Restrictive left ventricular filling MFVP in dilated cardiomyopathy assessed by Doppler echocardiography: clinical, echocardiographic and hemodynamic correlations and prognostic implications. J Am Coll Cardiol. 1993;22:808-815.[Abstract]
-
Xie GY, Berk MR, Smith MD, Gurley JC, De Maria AN. Prognostic value of Doppler transmitral flow patterns in patients with congestive heart failure. J Am Coll Cardiol. 1994;24:132-139.[Abstract]
-
Rihal CS, Nishimura RA, Hatle LK, Bailey KR, Tajik AJ. Systolic and diastolic dysfunction in patients with clinical diagnosis of dilated cardiomyopathy: relation to symptoms and prognosis. Circulation. 1994;90:2772-2779.
[Abstract/Free Full Text]
-
Pozzoli M, Capomolla S, Sanarico M, Pinna G, Cobelli F, Tavazzi L. Doppler evaluations of left ventricular diastolic filling and pulmonary wedge pressure provide similar prognostic information in patients with systolic dysfunction after myocardial infarction. Am Heart J. 1995;129:716-725.[Medline]
[Order article via Infotrieve]
-
Pozzoli M, Capomolla S, Cobelli F, Tavazzi L. Reproducibility of Doppler indices of left ventricular systolic and diastolic function in patients with severe chronic heart failure. Eur Heart J. 1995;16:194-200.
[Abstract/Free Full Text]
-
Lavine SJ, Campbell CA, Held AC, Johnson V. Effect of nitroglycerin-induced reduction of left ventricular filling pressure on diastolic filling in acute dilated heart failure. J Am Coll Cardiol. 1989;14:233-241.[Abstract]
-
Suzuki T, Sato K, Aoki K. Influence of postural change on transmitral flow velocity profile assessed by pulsed Doppler echocardiography in normal individuals and in patients with myocardial infarction. Am Heart J. 1990;120:110-115.[Medline]
[Order article via Infotrieve]
-
Hayashi K, Dote K, Sunaga Y, Sugiura T, Iwasaka T, Inada M. Evaluation of preload reserve during isometric exercise testing in patients with old myocardial infarction: Doppler echocardiographic study. J Am Coll Cardiol. 1991;17:106-111.[Abstract]
-
Pozzoli M, Capomolla S, Opasich C, Reggiani R, Calsamiglia G, Cobelli F, Tavazzi L. Left ventricular filling MFVP and pulmonary wedge pressure are closely related in patients with recent anterior infarction and left ventricular dysfunction. Eur Heart J. 1992;13:1067-1073.
[Abstract/Free Full Text]
-
Miyatake K, Izumi S, Okamoto M, Kinoshita N, Asonuma H, Nakagawa H, Yamamoto K, Takamiya M, Sakakibara H, Nimura Y. Semiquantitative grading of severity of mitral regurgitation by real time two dimensional Doppler flow imaging technique. J Am Coll Cardiol. 1986;7:82-88.[Abstract]
-
SAS Institute. SAS Technical Report P-229 SAS/STAT Software Changes and Enhancement (Release 6.07). Cary, NC: SAS Institute; 1992:633-679.
-
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;12:426-440.[Abstract]
-
Vanoverschelde JL, Raphael DA, Robert AR, Cosyns JR. Left ventricular filling in dilated cardiomyopathy: relation to functional class and hemodynamics. J Am Coll Cardiol. 1990;15:1288-1295.[Abstract]
-
Lavine SJ, Arends D. Importance of the left ventricular filling pressure on diastolic filling in idiopathic dilated cardiomyopathy. Am J Cardiol. 1989;64:61-65.[Medline]
[Order article via Infotrieve]
-
Lavine SJ, Campbell CA, Held AC, Johnson V. Effect of inotropic and vasodilator therapy on left ventricular diastolic filling in dogs with severe left ventricular dysfunction. J Am Coll Cardiol. 1990;15:1165-1172.[Abstract]
-
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;16:1175-1185.[Abstract]
-
Kono T, Sabbah HN, Rosman H, Shimoyama H, Alam M, Goldstein S. Divergent effects of intravenous dobutamine and nitroprusside on left atrial contribution to ventricular filling in dogs with chronic heart failure. Am Heart J. 1994;127:874-880.[Medline]
[Order article via Infotrieve]
-
Gaffney FA, Bastian BC, Thal ER, Atkins JM, Blomqvist CG. Passive leg raising does not produce a significant or sustained autotransfusion effect. J Trauma. 1982;22:190-193.[Medline]
[Order article via Infotrieve]
-
Reich DL, Konstadt SN, Raissi S, Hubbard M, Thys DM. Trendelenburg position and passive leg raising do not significantly improve cardiopulmonary performance in anesthetized patients with coronary artery disease. Crit Care Med. 1989;17:313-317.[Medline]
[Order article via Infotrieve]
-
Ross J Jr. Afterload mismatch and preload reserve: a conceptual framework for the analysis of ventricular function. Prog Cardiovasc Dis. 1976;18:255-264.[Medline]
[Order article via Infotrieve]
-
Buckberg GD, Fixler DE, Ardic JP, Hoffman JI. Experimental subendocardial ischemia in dogs with normal coronary arteries. Circ Res. 1972;30:67-81.
[Abstract/Free Full Text]
-
Taggart P, Sutton P, Lab M. Interaction between ventricular loading and repolarization: relevance to arrhythmogenesis. Br Heart J. 1992;67:213-215.
[Free Full Text]
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