Outcome of Subsequent Pregnancy in Patients With Documented Peripartum Cardiomyopathy Karen Sliwa, MD, PhD, Olaf Forster, MD, Fitzgerald Zhanje, MD, Geoff Candy, PhD, John Kachope, MD, and Rafique Essop, MD Subsequent pregnancy in 6 patients with previous peripartum cardiomyopathy resulted in reduction of ejection fraction by >10% in 5 patients at 1 month postpartum. Two patients with impaired ejection frac- tion at onset of subsequent pregnancy died 3 months postpartum due to heart failure despite optimal med- ical therapy. Deterioration of left ventricular function occurred uniformly postpartum and was accompa- nied by elevation of tumor necrosis factor- plasma levels from 2.4  1.1 pg/ml at onset of subsequent pregnancy to 6.2  2.4 pg/ml at 1 month postpartum. 2004 by Excerpta Medica, Inc. (Am J Cardiol 2004;93:1441–1443) P eripartum cardiomyopathy (PC) is a disorder of unknown origin in which symptoms of heart fail- ure occur between the last month of pregnancy and 5 months postpartum. A high mortality rate and overall poor clinical outcome has been reported in a high percentage of these patients. 1–5 Similar to other causes of heart failure, 6–8 we found elevated plasma levels of tumor necrosis factor (TNF)-, interleukin-6, and Fas/ Apo-1 (a marker of apoptosis) in this population. Although the definition of PC specifies the develop- ment of clinical heart failure within a defined time period, the occurrence and timing of objective left ventricular dysfunction in relation to symptoms and gestation period are unknown. Between November 1996 and March 2001 we prospectively followed 6 patients who became pregnant for a second time from a previously published cohort of 59 consecutive black patients with documented PC 1 attending the Cardiac Clinic at Chris Hani Baragwanath Hospital. Serial echocardiography and TNF- measurements were performed. ••• Inclusion criteria were: (1) age 16 and 40 years, (2) New York Heart Association functional class II to IV, (3) symptoms of congestive heart failure that developed in the last month of pregnancy or in the first 5 months postpartum, (4) no other identifiable cause for heart failure, (5) left ventricular ejection fraction 40% by transthoracic echocardiography, and (6) sinus rhythm. Exclusion criteria were: (1) significant organic valvu- lar heart disease, (2) systolic blood pressure 170 mm Hg and/or diastolic blood pressure 105 mm Hg, and (3) clinical conditions other than cardiomyopathy that could increase the cytokine levels, (i.e., rheumatoid ar- thritis, sepsis, acquired immunodeficiency syndrome). Clinical assessment, echocardiography, and cyto- kine measurements were performed at baseline and after 6 and 12 months of therapy. All patients received treatment with digoxin, diuretics, enalapril, and carve- dilol. Patients attended the cardiac clinic monthly. They were advised to avoid new pregnancies and were followed up prospectively. In the group of patients with subsequent pregnancy, echocardiography was performed at 8 weeks and 8 months of pregnancy and 1 and 3 months postpartum. At the same time inter- vals, blood was taken for cytokine measurements. The protocol was approved by the Committee for Research on Human Subjects of the University of the Witwa- tersrand. Fifteen milliliters of blood was drawn from an antecubital vein and collected into prechilled evacu- ated tubes containing ethylenediaminetetraacetic acid. Plasma was separated by centrifugation at 2,500 rpm for 12 minutes within 15 minutes of collection; the aliquots were frozen at -70°C. TNF- measurements were performed using a commercially available en- zyme-linked immunoassay (Amersham, Maidstone, United Kingdom). In addition, plasma was obtained from 20 age-matched healthy black volunteers. Two-dimensional targeted M-mode echocardiogra- phy with Doppler color flow mapping was performed using a Hewlett Packard Sonos 5500 echocardiograph (Philips, Bothell, Washington) attached to a 2.5- or 3.5-MHz transducer. All studies were recorded on videotape and were done by the same operator. Left ventricular dimensions were measured according to the American Society of Echocardiography guide- lines. 9 For left ventricular measurements, an average of 3 beats were obtained. Left ventricular ejection fraction was determined as previously described. 10 Data are presented as mean  SD. Wilcoxon matched pairs test was used for comparison of base- line data and the results 1 and 3 months after subse- quent pregnancy. Data were analyzed on a personal computer using a commercially available statistical program (Statistica, Tulsa, Oklahoma). Significance was assumed at a 2-tailed value of p 0.05. All 6 patients were indigenous black women (age range 26 to 39 years). Four patients were para 2, gravida 2, and 2 were para 3, gravida 3. The subse- quent pregnancy occurred 1 to 2 years after the initial pregnancy in all patients. None were twin or multiple From the Department of Cardiology, Chris Hani Baragwanath Hospi- tal, University of the Witwatersrand, Johannesburg, South Africa. This study was supported by the H.E. Griffith Trust and the University of the Witwatersrand Research Council, Johannesburg, South Africa. Dr. Sliwa’s address is: Department of Cardiology, Chris Hani Barag- wanath Hospital, Bertsham 2013, Johannesburg, South Africa. E-mail: hahnle@netactive.co.za. Manuscript received November 13, 2003; revised manuscript received and accepted February 12, 2004. 1441 ©2004 by Excerpta Medica, Inc. All rights reserved. 0002-9149/04/$–see front matter The American Journal of Cardiology Vol. 93 June 1, 2004 doi:10.1016/j.amjcard.2004.02.053