Contractile reserve in patients with peripartum cardiomyopathy and recovered left ventricular function

Contractile reserve in patients with peripartum cardiomyopathy and recovered left ventricular function Mark B. Lampert, MD, Lynn Weinert, BS, Judy Hibbard, MD, Claudia Korearz, DVM, Marshall Lindheimer, MD, and Roberto M. Lang, MD Chicago, Illinois OBJEOTIVI=$" Peripartum cardiomyopathy is a rare complication of pregnancy. Thirty percent of patients with this disorder are reported to recover baseline ventricular function within 6 months of delivery, but the ability of these ventricles to respond to hemodynamic stress is unknown. The aim of this investigation was to quantitatively assess the contractile reserve of patients with a history of peripartum cardiomyopathy and recovered left ventricular function. STODu DE$16N: Baseline left ventricular contractility was assessed by use of the load and heart rateindependent relationship between end-systolic stress and rate-corrected velocity of fiber shortening. Data were acquired from "recovered" patients (10.5 • 11.6 months after delivery) and compared with data from matched nonpregnant controls with use of two-dimensionally targeted M-mode echocardiography and calibrated subclavian pulse tracings that were recorded over a wide range of afterloads (end-systolic stress) generated by methoxamine (1 mg/min) infusion. Contractile reserve was assessed by a dobutamine challenge (5 ~g/kg/min) and quantified as the vertical deviation of the dobutamine endsystolic stress minus the corrected velocity of fiber shortening data point from the baseline contractility line. RE$1JI.T$: Patients with peripartum cardiomyopathy and matched controls had normal baseline heart rates, blood pressures, ventricular dimensions, and left ventricular function. Contractile reserve, however, was reduced in patients with recovered peripartum cardiomyopathy (0.30 • 0.12 vs 0.17 _+ 0.04 circ/sec, p < 0.03). CONCLUSIONS: Women with a history of peripartum cardiomyopathy who have regained normal resting left ventricular size and performance have decreased contractile reserve revealed by the use of a dobutamine challenge test. Ventricles of these women may respond suboptimally to hemodynamic stress in spite of evidence of recovery by routine echocardiographic evaluation. (Am J Obstet Gynecol 1997; 176:189-95.)

Key words: Peripartum cardiomyopathy, left ventricular function, contractile reserve

Peripartum cardiomyopathy, a rare disorder of unknown etiology, is seen in late pregnancy or in the early puerperium. ~ This disease entity was described as early as 18492 but was not well characterized until 1971 when Demakis et al. ~ established their landmark diagnostic criteria. Risk factors for the development of the disease include advanced maternal age, multiparity, black race, multiple fetuses, and a history of preeclampsia. "~5 The reported incidence of peripartum cardiomyopathy varies between 1:100 and 1:15,000 live births 1' 6; the wide range is believed to be the result of geographic differences and variations in the m a n n e r in which authors define the From the Noninvasive Cardiac Imaging Laboratory, Section of Cardiology, Departments of Medicine and Obstetrics and Gynecology, University of Chicago Medical Center. Received for publication January 16, 1996; ~fised July 22, 1996; acceptedJuly 31, 1996. Reprint requests:RobertoM. Lang, MD, University of Chicago Medical Center, 5841 S. Maryland Ave., Chicago, IL 6063Z Copyright 9 1997 by Mosby-Year Book, Inc. 0002-9378/97 $5.00 + 0 6/1/76974

syndrome.I, v Current management includes dietary salt restriction, diuretics, digoxin, and vasodilators. 8 In spite of such interventions, the mortality, rate remains at approximately 30%, and in patients surviving the initial episode of cardiac failure nearly half have persistent left ventricular dysfunction with a long-term prognosis that appears to be similar to that of heart failure from other causes?' 9. 10 Patients who regain left ventricular function usually do so within 6 months of the initial diagnosis, 1 and the prognosis of these "recovered" patients is significantly better than that of those with persistent left ventricular dysfunction. However, controversy in the literature exists regarding the management of subsequent pregnancy in these patients. Some investigators report redevelopment of the disease during subsequent pregnancies1' 4, n and proscribe conceiving again. O n the other hand, others have suggested that when clinical and echocardiographic parameters have normalized in patients with a previous history of peripartum cardiomyopathy subsequent preg189

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Lampert et al.

nancy is without significant risk) ~ In this respect, we are unaware of reports that focus on left ventricular function both during baseline conditions and under pharmacologically induced stress in recovered peripartum cardiomyopathy patients. The aim of this investigation therefore was to obtain objective data on the hemodynamic response to a challenge with the [3-agonist dobutamine in patients with a history of peripartum cardiomyopathy and recovered left ventricular size and performance. Methods Patient selection and controls. Peripartum cardiomyopathy was suspected in 27 women referred to our laboratory between 1985 and 1993. A firm diagnosis was established in 21 of them who satisfied all the following criteria (modified from Demakis et al.S): (1) development of cardiac failure in the last month of pregnancy or within 5 months of delivery, (2) absence of a determinable cause for the cardiac failure, (3) absence of demonstrable heart disease before the last month of pregnancy, and (4) echocardiographic evidence of impaired left ventricular systolic function as defined by left ventricular enlargement (left ventricular end-diastolic dimension ~5.7 cm) in association with a reduction of left ventricular fractional shortening (percent change -<22%). In each case the clinical history was verified, and the two-dimensional Doppler echocardiographic studies performed at diagnosis and during follow-up intervals were reviewed. Of the 21 original patients, 3 were lost to follow-up and the remaining 18 were sequentially studied over the past 8 years with serial echocardiograms. At least 55% (10/18) regained left ventricular function, whereas 45% (8/18) had persistent ventricular dysftmction. The mean time from presentation to recovery was 1.2 _+ 1.0 months. Seven of the 10 recovered patients participated in this study. Each study patient was matched to a normal nonpregnant control according to age, race, parity, and the presence of multiple fetuses. These controls were identified by searching a computer database of deliveries performed in the Department of Obstetrics and Gynecology at the University of Chicago Hospital. Once identified, the controls were then screened with a thorough medical history and echocardiogram to exclude the presence of hypertension, left ventricular hypertrophy, coronary artery disease, and myocardial dysfunction. Controls were also excluded if they were taking medications that could interfere with cardiac function. The experimental protocol, approved by the Institutional Review Board at the University of Chicago Hospitals and Clinics, was explained to each patient and control subjects who gave informed consent in writing before the beginning of the study. Data acquisition. Ultrasonographic imaging (HewlettPackard Sonos 1500, Andover, Mass.) was performed

January 1997 AmJ Obstet Gynecol

from the parasternal short axis transducer position with either a 2.5 or 3.5 MHz transducer with the beam directed just off the tip of the anterior mitral valve leaflet. All tracings were recorded at held end-expiration with the patient in the left lateral decubitus position. Simultaneous recordings of (1) two dimensionally targeted M-mode echocardiograms of the left ventricular cavity in the short axis, (2) phonocardiogram, (3) electrocardiogram (ECG), (4) subclavian pulse tracing, (5) noninvasive blood pressure measurement, and (6) continuous-wave Doppler imaging with two-dimensional echocardiographic measurement of the aortic annulus were acquired. The subclavian pulse tracing was obtained with use of a small plastic funnel positioned over the right subclavian artery at its point of maximal impulse in the supraclavicular fossa and connected with Silastic silicone rubber (Dow Corning) tubing to a strain-gauge transducer (model 03040170, Cambridge Instrument, New York). This tracing was calibrated according to the proximal brachial artery pressure obtained with an oscillometric sphygmomanometer-based system (Dinamap vital signs monitor, model 1846 SX, Criticon, Tampa). By setting the noninvasively determined aortic peak systolic pressure to the peak of the subclavian pulse tracing and the aortic diastolic pressure to the nadir of the pulse tracing, it was possible to obtain left ventricular endsystolic pressure by linear interpolation to the height of the incisura (i.e., dicrotic n o t c h ) , 1245 a method of calibration shown to be accurate over a wide range of systemic arterial pressures and cardiac outputs. Fig. 1 is an example of a two-dimensionally targeted M-mode echocardiogram recorded simultaneously with a subclavian pulse tracing. Noninvasively determined cardiac outputs were obtained from continuous-wave Doppler recordings and two-dimensional echocardiographic measurements of the aortic annular area. Aortic blood velocity was obtained with a 1.9 MHz continuous-wave Doppler transducer (Hewlett-Packard, Andover, Mass.) positioned at the cardiac apex. The aortic annular diameter in centimeters was measured as the distance separating the bases of the noncoronary and right coronary cusps of the aortic valve (trailing to leading edges) from the parasternal long-axis view with a 2.5 MHz transducer. Diameter was assumed to be constant throughout the cardiac cycle. ~6 The annular crosssectional area was calculated, assuming a circular orifice, as Cross-sectional area = ~r(Aortic annular diameter/2)2. Stroke volume was calculated as the product of the flow velocity integral and the cross-sectional area. 16 Protocol. After baseline measurements were obtained, left ventricular afterload was altered with methoxamine, an ~-specific agonist known to increase afterload by arterial vasoconstriction without direct cardiac effects) ~-15Before the initiation of the methoxamine infusion, patients were premedicated with atropine sulfate

Volume 176, Number 1, Part 1 AmJ Obstet Gynecol

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(0.01 m g / k g body weight) to abolish reflex cardiac slowing. T h e e~-agonist was then infused at a rate of 1 m g / m i n to increase ventricular afterload and enable the acquisition of multiple data points over a wide range of blood pressures. T h e ventricular response to arterial vasoconstriction was assessed with recordings taken every 1 to 2 minutes until peak systolic pressure had increased 20 to 40 m m H g above baseline. All data points were acquired at similar heart rates (within 10 b e a t s / m i n o f each other), and a m i n i m u m of f o u r points was recorded, after which the m e t h o x a m i n e infusion was discontinued. T h e peak pressor effect lasted 2 to 5 minutes. After recovery o f baseline hemodynamics, d o b u t a m i n e , a 13-agonist known to increase contractility and heart rate, was infused (5 I x g / k g / m i n ) for 5 minutes. H e m o d y namic recordings were then r e p e a t e d and the infusion discontinued. Data analysis. Left ventricular end-systolic dimension, end-diastolic dimension, and end-systolic and diastolic wall thicknesses were m e a s u r e d f r o m the echocardiographic recordings as described previously. 1~16 T h e left ventricular p e r c e n t of fractional shortening was calculated in the usual m a n n e r . T h e left ventricular ejection time was m e a s u r e d f r o m the onset o f the upstroke to the incisura of the s u p e r i m p o s e d subclavian pulse tracing.

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O'eSm (g/cm 2) Fig. 2. Shown is example of quantitative relationship between derived index values of ventricular afterload (~e+,~) and performance (Vcf). Baseline contractility was determined for each patient by plotting data points generated during wide range of afterloads induced by methoxamine infusion. Linear regression analysis was then used to construct baseline contractility line. Dobutamine (DOB)infusion results in upward shift of data point relative to baseline contractility line. Contractile reserve was quantified as vertical deviation from baseline contractility line to dobutamine-(corrected velocity of circumferential shortening) point.

Overall, left ventricular p e r f o r m a n c e was quantified by c o m p u t i n g the rate of c o r r e c t e d velocity of circumferential fiber shortening (in circulation p e r second) so that Vcfc = % A D / ( E T c / % / R R ) , where VcfC is the c o r r e c t e d velocity of circumferential fiber shortening, AD is fractional shortening, ET c is c o r r e c t e d ejection time, and RR is the interval between cardiac cycles d e t e r m i n e d f r o m the ECG. 13' 14 Left ventricular m e r i d i o n a l end-systolic wall stress was quantified by the following angiographically validated formulal~-15: e%sm = (0.338) (Pe+) (Des/ (he+)(1 + [h~s/De+] ), where ~ .... is left ventricular end-systolic afterload (in grams p e r square centimeter), P~ is end-systolic aortic pressure (in millimeters of mercury), and D~s and he+ are ventricular end-systolic dimensions and thicknesses, respectively (in centimeters). Previous studies using this integrated noninvasive a p p r o a c h to the assessment of left ventricular function and contractile reserve have shown minimal interobserver and intraobserver variability. 13~15 Baseline left ventricular contractile state was assessed with the l o a d - i n d e p e n d e n t relationship between endsystolic wall stress and rate-corrected velocity of circumferential fiber s h o r t e n i n g (left ventricnlar end-systolic afterload - c o r r e c t e d velocity o f circumferential fiber shortening) (Fig. 2). 14 This relationship, d e t e r m i n e d by linear regression analysis (least squares m e t h o d ) with a m i n i m u m of four data points acquired u n d e r baseline conditions and over a wide range o f afterloads g e n e r a t e d by the m e t h o x a m i n e infusion is a sensitive i n d e x o f left

192 Lampert et al.

JanumT 1997 Am J Obstet Gynecol

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Fig. 3. Recovery of left ventricular function in patient with peripartum cardiomyopathy. Left, M-mode echocardiogram obtained at diagnosis in patient with peripartum cardiomyopathy. Left ventricular performance after clinical recovery is shown on right, which demonstrates significant reduction in heart rate (HR) and chamber dimension and marked improvement in fractional shortening. ESD, End-systolic dimension; EDD, enddiastolic dimension; %AD, percent fractional shortening.

v e n t r i c u l a r contractility t h a t is i n d e p e n d e n t of p r e l o a d a n d h e a r t rate while i n c o r p o r a t i n g a f t e r l o a d i n t o its analysis. ~4 C o n t r a c t i l e reserve was d e f i n e d as t h e vertical deviation ( c h a n g e in c o r r e c t e d velocity of c i r c u m f e r e n tial f i b e r s h o r t e n i n g (in circulation p e r s e c o n d ) b e t w e e n the b a s e l i n e contractility line a n d t h e d o b u t a m i n e - i n d u c e d data p o i n t (Fig. 2). Previous d a t a have s h o w n t h a t d o b u t a m i n e i n d u c e s a n u p w a r d shift of the contractility line w i t h o u t a c h a n g e in its slope. 14 S t a t i s t i c s . E a c h p a t i e n t was m a t c h e d with a c o n t r o l as described. I n t e r g r o u p c o m p a r i s o n s were d o n e with a n u n p a i r e d t test in w h i c h p < 0.05 was c o n s i d e r e d significant. G r o u p data are e x p r e s s e d as m e a n _+ SD. Results f e a t u r e s . T h e study p a t i e n t s with a history o f p e r i p a r t u m c a r d i o m y o p a t h y a n d r e c o v e r e d left v e n t r i c u l a r f u n c t i o n h a d a m e a n age o f 30.4 _+ 7.5 years, were m u l t i p a r o u s ( m e a n parity 2.9 -+ 1.6), a n d p r e d o m inantly black ( 6 / 7 ) . C o n t r o l s h a d similar f e a t u r e s ( m e a n age 32.4 -+ 8.0 years, parity 2.1 -+ 1.1, b l a c k race 6 / 7 ) . O n e p a t i e n t in e a c h g r o u p h a d a history o f m u l t i p l e fetuses. Fewer t h a n o n e t h i r d o f t h e p a t i e n t s ( 5 / 2 1 ) h a d cardiac failure d u r i n g t h e last m o n t h o f p r e g n a n c y . Sixteen p a t i e n t s h a d s y m p t o m s after delivery, t h e majority ( 1 0 / 1 6 ) d u r i n g t h e first 3 p o s t p a r t u m m o n t h s . Baseline hemodynamics. T a b l e I depicts the e c h o c a r Demographic

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PPCM, Peripartum cardiomyopathy; HR, heart rate; ESD, end-systolic dimension; EDD, end-diastolic dimension; SF, percent fractional shortening; CO, cardiac output; C1, cardiac index; SV, stroke volume; MAP, mean arterial pressure; TVR, total vascular resistance. All values are mean -+ SD.. *p < 0.05 compared with peripartum cardiomyopathy at study entry (however, values from both groups are within accepted normal limits).

d i o g r a p h i c i n d e x values of left v e n t r i c u l a r p e r f o r m a n c e in p a t i e n t s with p e r i p a r t u m c a r d i o m y o p a t h y a n d controls. At p r e s e n t a t i o n (which a v e r a g e d 2.8 -+ 2.8 weeks post p a r t u m ) , p a t i e n t s with p e r i p a r t u m c a r d i o m y o p a t h y h a d m a r k e d v e n t r i c u l a r dilatation, r e d u c t i o n o f systolic p e r f o r m a n c e , r e d u c e d cardiac o u t p u t , i n c r e a s e d total vascular resistance, a n d i n c r e a s e d h e a r t rate. I n contrast, all these i n d e x values h a d n o r m a l i z e d by t h e time o f study entry. T h e m e a n time to recovery was 1.2 -+ 1.0 m o n t h s , a n d t h e average time f r o m recovery to study e n t r y was 10.5 -+ 11.6 m o n t h s . As also s h o w n in T a b l e I, t h e h e m o d y n a m i c m e a s u r e m e n t s a m o n g study p a t i e n t s with r e c o v e r e d p e r i p a r t u m c a r d i o m y o p a t h y a n d t h o s e o f t h e age-, race-, a n d p a r i t y - m a t c h e d c o n t r o l s all fell within t h e n o r m a l range. Interestingly, t h e diastolic v e n t r i c u l a r d i m e n s i o n s were slightly larger, a n d t h e s h o r t e n i n g f r a c t i o n slightly g r e a t e r in t h e r e c o v e r e d p a t i e n t s with p e r i p a r t u m c a r d i o m y o p a t h y . E c h o c a r d i o g r a p h i c a l l y derived p a r a m e t e r s o f cardiac o u t p u t , stroke v o l u m e , a n d total v a s c u l a r resistance were i n d i s t i n g u i s h a b l e a m o n g the two g r o u p s at baseline. Fig. 3 depicts a n M - m o d e e c h o c a r d i o g r a m p e r f o r m e d o n a study p a t i e n t at diagnosis a n d after recovery o f left v e n t r i c u l a r f u n c t i o n . O n p r e s e n t a t i o n , t h e p a t i e n t was tachycardic a n d h a d i n c r e a s e d c h a m b e r d i m e n s i o n s a n d m a r k e d r e d u c t i o n o f v e n t r i c u l a r fractional s h o r t e n i n g . After recovery t h e h e a r t rate was substantially r e d u c e d , w h e r e a s c h a m b e r d i m e n s i o n s h a d d e c r e a s e d a n d fractional s h o r t e n i n g h a d i m p r o v e d to t h e n o r m a l range. C o n t r a c t i l e reserve. Fig. 4 depicts t h e m e a s u r e d contractile reserve values for e a c h p a t i e n t a n d t h e corres p o n d i n g m a t c h e d control. O f note, the m e a s u r e d contractile reserve in the recovered p e r i p a r t u m cardiomyopathy

Lampert et a[.

Volume 176, Number 1, Part 1 Am J Obstet Gynecol

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Fig. 4. Contractile reserve among recovered patients with peripartum cardiomyopathy and controls (CTR). Contractile reserve was defined as vertical deviation (change in rate-corrected velocity of circumferential fiber shortening in circulation per second) between baseline contractility line and dobutamineinduced shift in data point (see Fig. 2). Contractile reserve (AVcf) values are depicted for study patients (open circles) and respective controls (closed circles)each matched for age, race, and parity (lines). Contractile reserve was significantly lower in patients with history of peripartum cardiomyopathy and recovered left ventricular function than in controls (p < 0.03). PPCM, Peripartum cardiomyopathy with recovered left ventricular function.

patients was consistently lower than that of the m a t c h e d control, representing r e d u c e d contractile reserve in patients with recovered p e r i p a r t u m cardiomyopathy. T h e r e was also a significant difference (p < 0.03) between the m e a n contractile reserve of each g r o u p in spite of substantial intersubject variability in contractile reserve values within the control population. Also, these results were obtained with d o b u t a m i n e infused at 5 btg/kg/min, a minimal dose c o m p a r e d with standard clinical dobutamine stress testing) 7

Comment We used a d o b u t a m i n e challenge test to characterize contractile reserve in w o m e n who had apparently recovered ventricular fimction after p e r i p a r t u m cardiomyopathy. These patients had baseline ventricular size and p e r f o r m a n c e indistinguishable f r o m carefully selected age-, race-, and parity-matched controls, but their "recovered" ventricles had significantly r e d u c e d contractile reserve. Thus w o m e n with p e r i p a r t u m cardiomyopathy, said to have recovered, have a subclinical residual abnormality of systolic function that does n o t b e c o m e evident until the myocardium is subjected to significant h e m o dynamic stress. F u r t h e r m o r e , the d o b u t a m i n e challenge of but 5 I x g / k g / m i n acutely mimicked some of the chronic physiologic cardiovascular adaptations to pregnancy,

-10 -30 40

Fig. 5. Comparison of hemodynamic changes induced by dobutamine (DOB) in patients with recovered peripartum cardiomyopathy (PPCM) and in normal pregnancy (CTR). These results depict percent change in heart rate (HR), cardiac output (CO), and total vascular resistance (TVR) in (1) 7 patients with recovered peripartum cardiomyopathy after infusion of dobutamine (5 Ixg/kg/min) (clear bars) and (2) 15 normal pregnant women (hatched bars). In latter group percent change corresponds to those of second trimester (2TR) compared with 8 weeks post partmn (PP). Results are expressed as mean -+ SEM.

namely, increased heart rate and cardiac output, ts This may explain r e c u r r e n c e of symptoms during subsequent gestations in patients who have apparently recovered. In this investigation each patient with p e r i p a r t u m cardiomyopathy was diagnosed at our institution, the case history was verified by the authors, and patients were e x c l u d e d if they had c o n f o u n d i n g illnesses that may have contributed to the cardiac failure. In addition, all diagnostic and follow-up echocardiograms were p e r f o r m e d in our laboratory. Thus in every instance the clinical evaluation was supported by quantitative evidence of left ventricular dilation (left ventricular end-diastolic dimension 6.1 _+ 0.4 cm), systolic dysfunction (left ventricular fractional shortening 18.9% _+ 4.5%) (Table I), and the sequential i m p r o v e m e n t culminating in n o r m a l baseline values (left ventricular end-diastolic d i m e n s i o n 5.1 -+ 0.5 cm, left ventricular fractional shortening 0.35% + 0.03%) was also d o c u m e n t e d . T h e i m p o r t a n c e of this a p p r o a c h c a n n o t be overemphasized because errors in each of these crucial steps have contributed to confusion in the literature regarding incidence, risk factors, and prognosis of the disease. 6 In the past, for instance, diagnosis, based only on the clinical criteria p r o p o s e d by Demakis et al. 3 and without e c h o c a r d i o g r a p h i c d e m o n -

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stration of left ventricular systolic dysfunction, certainly led to the inclusion of patients with other disorders and may be a reason for discrepant reports regarding the course of these patients in subsequent pregnancies. This is underscored here because 22% of the women referred to this laboratory for peripartum cardiomyopathy did not have the disease. The dobutamine challenge test, as used in this study, permits speculation concerning cardiac performance in subsequent pregnancies. Normal gestation is characterized by striking changes in the cardiovascular system, including intravascular volume expansion and increments in cardiac output and end-diastolic dimension (i.e., preload) and heart rate but a marked decrement in peripheral resistance, is' 19 There is also a physiologic anemia ~9 and an increase in the basal metabolic rate. These hemodynamic stressors characteristic of normal uncomplicated gestation are one reason patients with subclinical valvular, ischemic, or myopathic heart disease have a tendency to decompensate, often at midgestation, the period when increments in blood volume and cardiac output have peaked. 2~ We undertook the current study hypothesizing that our "recovered" patients might also harbor subclinical disease not apparent in routine baseline testing and challenged them with dobutamine, which produces acute changes that mimic several cardiovascular alterations in pregnancy. 21 It is of interest to compare the hemodynamic alterations produced by dobutamine infusion (5 p~g/kg/min) in women with "recovered" peripartum cardiomyopathy with those occurring in normal gestation. Fig. 5 compares the changes produced by dobutamine with those of 15 second-trimester normotensive women who are currently participating in another study that requires serial measurement of cardiac dynamics throughout gestation and 2 months post partum. The acute changes produced by dobutamine, including a 21% and a 26% increase in heart rate and cardiac output, respectively, compare well with the chronic alterations in these parameters during pregnancy. Dobutamine also decreases peripheral resistance, although only about half that during gestation. One difference, however, between hemodynamic changes seen with dobutamine compared with gestation is the increment in contractility produced by the inotropic agent. We have previously demonstrated that contractility remains unaltered during late pregnancy. 22 Nevertheless, the similarities are sufficient to permit speculation that these women, shown to have subclinical systolic dysfunction, would be at considerable risk if they conceive again. Prognosis and treatment. In the United States the reported mortality of peripartum cardiomyopathy ranges from 25% to 50%.3' 9, 10 Nearly half these deaths, primarily from chronic progressive congestive heart failure, arrhythmia, or thromboembolic complications, occur

January 1997 AmJ Obstet Gynecol

within the first 3 postpartum months; the mortality of embolic p h e n o m e n a has been reported to be as high as 30%fl, 9, 10 Few data on prognostic variables2a24 have been reported in patients who have recovered from this syndrome. Anecdotally, it has been suggested that prognosis, as in other forms of heart failure, is related to left ventricular size 23' 24 or the severity of the left ventricular dysfunction at the time of initial presentation. Apparently hearts destined to recover normal function do so within 6 months from the time of initial diagnosis, 3 and this was true of our patients, whose recovery averaged 1.2 -+ 1.0 months. Importantly, patients who have recovered left ventricular function have significantly improved survival.2a. 24 Most authors agree that patients with peripartum cardiomyopathy and persistent left ventricular dysfunction are at extremely high risk for complications and death should they become pregnant again. In contrast, the issue of whether patients with peripartum cardiomyopathy and recovered left ventricular function can safely undergo subsequent pregnancy remains controversial. The abnormality identified in this study may help explain the adverse outcomes documented in several case reports of subsequent pregnancy in recovered peripartum cardiomyopathy patients. Limitations. Although the lower contractile reserve in patients with "recovered" peripartum cardiomyopathy was significant, the sample size of our study was small. This is because the incidence of peripartum myopathy is very low in the general population, and even tertiary referral centers in high-risk urban centers such as ours have limited access to these patients. Needed are multicenter studies, or at least a registry. We believe that the best quantitative approach to these patients is the measurement of contractile reserve, quantifying this parameter by the change in rate-corrected velocity of fiber shortening by use of a single dobutamine data point. Previous studies have demonstrated that this method is feasible because dobutamine has causes an upward shift of the contractility line without a change in its slope. 16 Our data demonstrate that patients with a history of peripartum cardiomyopathy who have regained normal resting left ventricular size, performance, and hemodynamics have reduced contractile reserve, measured quantitatively by the use of a dobutamine challenge test. Thus, in spite of apparent recovery, the ventricles may respond suboptimally to hemodynamic stress. Caution is therefore required in recommendations regarding the safety of subsequent pregnancy in patients with a previous history of peripartum cardiomyopathy even when baseline function is normal. Should patients conceive, serial noninvasive monitoring of cardiac function is recommended. REFERENCES

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2. Richie C. Clinical contribution to the pathology, diagnosis and treatment of certain chronic diseases of the heart. Edinb Med SurgJ 1849;2:333-42. 3. Demakis JG, Rahimtoola SH, Sutton GC, Meadows WR, Szanto PB, Tobin JR, et al. Natural course of peripartum cardiomyopathy. Circulation 1971;44:1053-61. 4. Seftel H, Susser M. Maternity and myocardial failure in African women. Br H e a r t J 1961;23:43-52. 5. Hull E, Hafkesbring E. '~ postpartal heart disease. New Orleans Med SurgJ 1937;89:550-7. 6. Cunningham FG, PritchardJA, Hankins GD, Anderson PL, Lucas MJ, Armstrong KF. Peripartum heart failure: idiopathic cardiornyopathy or compounding cardiovascular events? Obstet Gynecol 1986;67:157-68. 7. Sanderson JE, Adesanya CO, Anjorin FI, Parry EO. Postpartum cardiac failure-heart failure due to volume overload. Am H e a r t J 1979;97:613-21. i 8. Lee W. Clinical management of gravid women with perlparturn cardiomyopathy. Obstet Gynecol Clin North Am 1991; 18(2):257-271. 9. Walsh j[], Burch GE, Black WC, Ferrans VJ, Hibbs RG. Idiopathic myocardiopathy of the puerperium (postPartal heart disease). Circulation 1965;32:19-31. 10. Meadows WR. Idiopathic myocardial failure in the last trimester of pregnancy and the puerperium. Circulation 1957;15:903-14. 11. Sutton MS, Cole P, Piappert M, Saltzman D, Goldhaber S. Effects of subsequent pregnm~cy on left ventricular carldiomyopathy. Am H e a r t J 1991;121:1776-8. 12. Borow KM, Newburger J. Noninvasive estimation of central aortic pressure using the oscillometric method for analyzing systemic artery pulsatile blood flow: comparative study of indirect systolic, diastolic, and mean brachial artery pressure with simultaneous direct ascending aortic pressure measurements. Am H e a r t J 1982;103:879-86. 13. Lang RM, Fellner SK, Neumann A, Bushinsky DA, Borow KM. Left ventricular contractility varies directly with blood ionized calcium. Ann Intern Med 1988;108:524-9. 14. Colan SD, Borow KM, Neumann A. The left ventricular end

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