BBIEF REPORTS

velopment, presumably related to exposure of subintimal type I collagen and release of thrombotic mediators.’ Nonetheless, our early clinical experience demonstrates no significant acute thrombotic events with deep tissue resection when aspirin and high dose heparin are used.

Clinical data from the balloon angioplasty experience suggest that the degree of residual stenosis may be an important factor in predicting restenosis for some lesions.2 Animal data have demonstrated that platelet deposition, an important hemorrheologic factor in coro- nary restenosis,’ is a function of shear rate,3 which is determined by luminal diameter at any given flow rate. Therefore, minimizing residual stenosis may limit plate- let deposition at the atherectomy site. Reduced turbu- lence resulting from removal of the atheroma may also be of benefit.

We observed medial elements in 51% of resected vas- cular tissues, and identified adventitia in 3oo/o of speci- mens. These data suggest that deep (subintimal) reset- tion of vascular tissues during coronary atherectomy pro- cedures does not result in acute thrombotic, hemorrhagic or occlusive complications. The long-term effects of deep arterial resection remain unknown.

1. Chesebro JH, Lam JYT, Bedimon L, Faster V. Restenosis after arterial angioplasty: a hemorrheologic response to injury. Am J Cardiol 1987,6O:lOB- 168. 2. Leimgruber PP. Roubin GS, Hollman J, Cotsonis GA, Meier B, Douglas JS, Kina SB. Gruentzie AR. Restenmis after successful coronarv aneioulastv in patients with sing1e‘;esse.l disease. Circulation 3987;73:710-717. - . I 3. Badion L, Badimon JJ, Galvez A, Chesebro JH, Fuster V. Influence of arterial damage and wall shear rate on platelet deposition. Arreriosclerosis 1986.6.312-320.

Prognosis in Peripartum Cardiomyopathy Antonio Carvalho, MD, Anselmo Brandao, MD, Eulogio E. Martinez, MD, Dimitrios Alexopoulos, MD, Valter C. Lima, MD, Jose L. Andrade, MD, and John A. Ambrose, MD

P eripartum cardiomyopathy is a rare disease of unknown etiology. Risk factors for its development

include increased maternal age, black race, multiparity, twinning, malnutrition, toxemia and hypertension.‘*2 The mortality rates in the acute and subacute phases range from 30 to 60%.3 The prognosis is especially poor in patients with significant cardiomegaly persisting >6 months and in patients with low left ventricular (LV) ejection fraction. 4,5 Other noninvasive or clinical charac- teristics affecting severity and prognosis of the disease have not been well defined. We describe our experience with 19 consecutive patients with peripartum cardiomy- opathy who were prospectively evaluated in Sao Paolo, Brazil.

Between January 1982 and June 1988, 19 patients (12 white, 7 black, mean age 26 years, range 18 to 40) with peripartum cardiomyopathy were admitted to Es- cola Paulista de Medicina. Upon admission all patients were in New York Heart Association functional class IV. Peripartum cardiomyopathy was defined as the develop- ment of heart failure for thefirst time during the third trimester of pregnancy without a history of or evidence for, significant valvular, hypertensive or ischemic heart disease. All patients gave no history of excessive alcohol intake and had negative serologic tests for Chagas’ dis- ease.

Patients’ evaluation included history, physical exam- ination, 12-lead electrocardiogram, chest x-ray (in the posteroanterior and left lateral projections) and M- mode or 2-dimensional echocardiogram. Right ventricu- lar myocardial biopsies were obtained from 13 patients.

From the Department of Cardiology, &cola Paulista De Medicina, Rua Pscobar Ortiz 699, Sao Paulo, SP 045 12, Brazil, and the Division of Cardiology, Department of Medicine, Mount Sinai Hospital, New York, New York. Dr. Alexopoulos is an Annenberg Scholar in Cardiol- ogy, Mount Sinai Hospital. Manuscript received March 13, 1989; re vised manuscript received May 22,1989, and accepted May 30.

540 THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 64

None of our patients had clinical evidence of malnu- trition or a history of viral-like symptoms before the onset of symptoms of heart failure. Four patients were smokers and 5 patients had only mild hypertension dur- ing pregnancy. All patients presented to the hospital within 1 week after onset of symptoms. At the time of hospital admission physical examination revealed jugu- lar venous distension in 15, hepatomegaly in 15, pedal edema in 16 and ascites in 3 patients. An S3 gallop rhythm was present in 15 and a mitral holosystolic mur- mur in 7 patients.

Patients were followed up for an average of 21 (range 6 to 72) months after initial admission. Patients were divided in 2 groups depending on their clinical status at follow-up. Group A consisted of 8patients who remained in functional class Z or ZZ, and group B consisted of 11 patients who either died, received cardiac transplanta- tion or remained in functional class ZZZ or IV.

Two-tailed unpaired t test and Fisher exact test were used for comparison of continuous and discrete vari- ables, respectively, between the 2 groups. All values are expressed as mean f 1 standard deviation. A p value KO.05 was considered significant.

Noninvasive laboratory findings included sinus rhythm in all patients on admission. The electrocardio- grams almost always exhibited nonspecific ST-T changes; they were normal in only 2 patients. Four pa- tients had voltage criteria for LV hypertrophy and 1 patient left atria1 enlargement. Two patients had left bundle branch block and 2 additional patients had left anterior hemiblock.

Good quality M-mode or 2-dimensional echocardio- grams were obtained within 24 to 48 hours of the initial hospital admission in 16 of 19 patients. The characteris- tic findings were LV dilation with reduced fractional shortening and normal LVwall thickness (Table Z). Left atria1 dimension was either normal or slightly increased.

TABLE I Clinical and Noninvasive Characteristics in Patients Who Improved (Group A) or Deteriorated or Failed to Improve (Group B) After Initial Clinical Presentation with Congestive Failure

Pt. Age No. Ws) Parity Onset of Symptoms

Group A 1 20 1 2 weeks postpartum 4 18 1 1 week postpartum 7 31 1 4 weeks postpartum

10 27 1 1 week postpartum 11 18 3 Seventh month of pregnancy 13 20 1 Eighth month of pregnancy 15 19 1 12 weeks postpartum 17 27 3 1 week postpartum Mean 22 SD 5

Group B 2 40 3 22 weeks postpartum 3 21 2 8 weeks postpartum

5 37 2 1 week postpartum 6 25 2 2 weeks postpartum 8 20 1 4 weeks postpartum 9 28 2 8 weeks postpartum

12 34 2 6 weeks postpartum 14 32 4 4 weeks postpartum 16 36 4 4 weeks postpartum 18 22 1 Seventh month of pregnancy 19 18 1 4 weeks postpartum Mean 28 SD 8

CTR = cardiothoradc ratio: LVEDD = left ventricular enddtastolic diameter (mm): SD = standard dewation; - = not available.

CTR LVEDD

0.63 60 - 62 0.61 52 - 46 0.52 65 0.60 63 0.52 66 0.59 52 0.58 58 0.05 7

70 0.68 -

0.58 72 0.62 60 0.68 - 0.66 -

0.53 62 0.67 70 0.68 79 0.66 69 0.65 74 0.64 69 0.05 6

One patient exhibited type A paradoxical septal motion. Small pericardial effusions were detected in 3 patients.

Right ventricular biopsy specimens were obtained an average of 8 months from the onset of symptoms in I3 of 19patients. No patient had a completely normal biopsy. The most frequent findings (hypertrophied myocardial

fibers, fibrosis and focal increase of inflammatory cells) were consistent with healing myocarditis. Signs of acute myocarditis were found in only 1 patient.

Patients in group A showed normalization of heart size (2 without medications and 6 receiving digoxin as the only medication). In group B, there were 7patients in functional class III or IV, receiving digoxin, furosemide and vasodilators (one of them awaiting heart transplan- tation). One patient had cardiac transplantation 9 months postpartum and 3 patients died 6, 24 and 28 months after delivery in congestive heart failure.

Patients in group B tended to be older than patients in group A, p KO.07 (Table I). There was a predominance of black women in group B compared to group A (54 us 12%, p X0.06). Multiparity, similarly, tended to be more frequent in group B than in group A patients (73 us 25% p KO.06). Two of 8 group A patients versus 8 of 1 I group Bpatients (p <0.05) had onset of symptoms later than 2 weeks postpartum. Cardiothoracic ratios at the time of hospital admission were larger in group B than in group A (Table I), p KO.03. The LVend-diastolic diameter was significantly larger in group B (Table I), p cO.005. Pul- monary thromboembolism occurred in I patient and ce- rebral embolism in 4 patients. All patients who had thromboembolic episodes were in group B.

Our observations confirm prior studies showing that peripartum cardiomyopathy is a disease of poor progno- sis. At follow-up 16% of our patients died and 50% of the

remaining patients had severe heart failure. Embolic epi- sodes occurred frequently (in 26% of our patients), which is similar to previous studies Mural thrombi are common on pathologic examinations in patients with peripartum cardiomyopathy and pulmonary and systemic emboliza- tions are not infrequent.‘T3

Only 1 patient had pathologic findings diagnostic of myocarditis. It is possible that a higher prevalence of myocarditis would have been found had the biopsies been performed earlier after the onset of symptoms.4,5 Of in- terest, in patients with a benign clinical course, myocardi- al biopsies revealed histologic abnormalities even when heart size had returned to normal.

As mentioned, this syndrome occurs more frequently in older, multiparous and black women. Because approxi- mately 80% of our obstetric clinic patients were white and <30 years old, the findings of a 37% incidence of black women and a 32% incidence of women >30 years old with this syndrome may not be inconsistent with prior studies. However, we found no association between multiparity and peripartum cardiomyopathy. Nine of our 19 patients (47%) were primiparous. Similarly, 57% of the 14 pa- tients reported by O’Connell et al5 were primiparous.

When patients were divided according to clinical out- come, LV end-diastolic diameter was found to be strongly associated with a poor prognosis. This finding is consis- tent with the data of O’Connell et a1.5 The larger LV end- diastolic dimension in patients with poor prognosis proba- bly indicated a greater degree of myocardial damage or more unfavorable loading conditions than in patients with good prognoses. Furthermore, prognosis was related to race, age and multiparity. Six of 7 black women and 75% of the multiparous women had a poor prognosis. All black multiparous women older than 30 years had poor clinical

THE AMERICAN JOURNAL OF CARDIOLOGY SEPTEMBER 1, 1989 541

BRIEF REPORTS

courses. This is the first series of patients with peripartum cardiomyopathy in whom a tendency to an association between known risk factors (age, multiparity and race) and bad prognosis is reported. The late (>2 weeks post- partum) onset of symptoms was also more frequent in patients with a poor prognosis. It is not clear from this study whether this finding could reflect different mecha- nisms involved in the pathogenesis of the disease.

In conclusion, increased LV end-diastolic diameter in the acute phase of peripartum cardiomyopathy and late postpartum onset of symptoms were associated with a poor prognosis. A trend toward poor prognosis was also seen in women who were black, multiparous and older

than 30 years. These findings warrant further confirma- tion with additional prospective studies.

1. Veille JC. Peripartum cardiomyopathies: a review. Am J Obster Gynecol 1984;148:805-818. 2. Cunningham FG, Pritchard JA, Hankins GDV, Anderson PL, Lucas MJ, Armstrong KF. Peripartum heart failure: idiopathic cardiomyopathy or com- pounding cardiovascular events? Obstet Gynecol 1986,67:157-167. 3. Homans DC. Peripartum cardiomyopathy. N Engl J Med 1985;312:1432- 1437. 4. Demakis JG, Rahimtolla SH, Sutton GG, Meadows R, Szanto PB, Tobin JR, Gunnar RM. Natural course of peripartum cardiomyopathy. Circulalion 1971; 44:1053-1061. 5. O’Connell JB, Costanzo-Nordin MR, Subramanian R, Robinson JA, Wallis DE, Scanlon PJ, Gunnar RM. Peripartum cardiomyopathy: clinical, hemody- namic, histologic and prognostic characteristics. JACC 1986;8:52-56.

Hemodynamic Effects of High Dose Naloxone in Congestive Heart Failure L. Allen Kindman, MD, and Michael B. Fowler, MB, MRCP

I n humans, the salutary properties of the opioid agonist morphine in the treatment of acute pulmonary edema

and chronic congestive heart failure (CHF) are well known. These are thought to be the result of vasodilata- tion and concomitant afterload reduction caused by bind- ing with centraP and peripheral4 opioid receptors. This clinical pharmacologic observation suggests that the en- dogenous opioid peptides have the potential to contribute favorably to the regulation of the hemodynamic response to acute and chronic CHF. However, contrary to the expectation based on the therapeutic efficacy of mor- phine, the endogenous opioids may actually exert a dele- terious effect on the hemodynamic response to cardiogen- ic shock and the syndrome of CHF.5,6 Case reports de- scribe dramatic hemodynamic improvement after the administration of low doses of the narcotic antagonist naloxone to patients suffering cardiogenic shock in the setting of an acute myocardial infarction.’

The hemodynamic effects of therapeutic (0.02 mg/ kg) or maximal (1 mg/kg) doses of naloxone have not been studied in patients with CHF. In normal volunteers naloxone at doses up to 1 mg/kg causes little alteration in blood pressure, heart rate or respiration.8 If endogenous opioids do play a role in the regulation of the hemody- namic response to chronic myocardial failure, alterations in resting hemodynamics after the administration of an opioid antagonist to patients with CHF should be identi- fied. We report the first study defining the hemodynamic consequences of a graded naloxone infusion in patients with CHF.

Six patients (4 men, 2 women, mean age 47 years, range 34 to 57) with stable clinical class II or III conges- tive heart failure (New York Heart Association) agreed

From the Cardiology Division, Department of Medicine, Stanford Uni- versity Medical Center, 300 Pasteur Drive, Stanford, California 94305. This study was supported by grant NRSA ST32 HL07265-10 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland; Dr. Kindman is a medical research fellow of the Bank of America Giannini Foundation. Manuscript received March 6, 1989; revised manuscript received May 22,1989, and accepted May 30.

542 THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 64

to participate. Because of the severity of symptoms or of adverse prognosticfactors, these patients were beingcon- sidered for orthotopic cardiac transplantation. All were in good health otherwise. All patients were in sinus rhythm. The mean duration of symptomatic CHF was 29 months (range 6 to 72). The etiology of left ventricu- lar failure was idiopathic dilated cardiomyopathy in 4 and was secondary to extensive myocardial infarction due to coronary artery disease in 2. The mean ejection fraction f standard deviation was 11.3 f 4.4% (range 6 to 19) by radionuclide angiography. The maximal oxy- gen uptake during a symptom-limited treadmill test (performed in 5 of the dpatients) was 14.2 f 1.8 ml/min/ kg (mean f standard deviation, range 12 to 17). None of the patients admitted to narcotic use within the week before the study. Informed consent was obtainedfrom all subjects in accordance with the directives of the Human Subjects Committee of Stanford University Medical Center.

All patients took their usual medications, including digoxin, furosemide, potassium ana’ captopril at clini- cally well-tolerated doses, before the study. All patients had been receiving a stable therapeutic regimen for at least 1 week before the study. Two were receiving pro- cainamide for nonsustained ventricular tachyarrhyth- mias. Patients were studied in the fasting state. Diaze- pam, 5 or 10 mg, was given orally as premeditation. Pulmonary arterial and right atrialpressures were mon- itored with a 7Frjlow-directed thermodilution catheter (Critikon) . Left ventricular pressure was monitored with either a Camino fiber optic catheter or a 6.7Fr endhole pigtail catheter maintained with comtant drip infusion when not being used for measurements. Systemic arteri- al pressure was monitored through the sideport of an 8Fr sheath through which the left ventricular catheter had been passed. Micron transducers were usedfor all deter- minations with fluid-filled catheters.

The following were determined: left ventricular V,,, the extrapolated velocity of contraction at zero load; Vpm, the maximum ratio of dP/dt/28P; T, the time