Predictors of outcome in 176 South African patients with peripartum cardiomyopathy.

OBJECTIVE: Identify novel prognostic factors for patients with peripartum cardiomyopathy (PPCM). DESIGN AND SETTING: Prospective cohort study conducted in a single tertiary care centre in South Africa. PATIENTS: 176 African women with newly diagnosed PPCM were studied. INTERVENTIONS: Clinical assessment, echocardiography and laboratory results were obtained at baseline and at 6 months. MAIN OUTCOME MEASURES: Poor outcome was defined as the combined end point of death, left ventricular (LV) ejection fraction (LVEF) < 35%, or remaining in New York Heart Association (NYHA) functional class III/IV at 6 months. Complete LV recovery was defined as LVEF ≥55% at 6 months. RESULTS: Forty-five (26%) patients had a poor outcome. Multiple logistic regression analysis revealed that, after adjustment for age, NYHA functional class, LVEF and systolic blood pressure, increased left ventricular end systolic dimension (LVESD), lower body mass index (BMI) and lower total cholesterol at baseline were independent predictors of poor outcome (adjusted OR 1.09, 95% CI 1.04 to 1.15, p=0.001; OR 0.89, 95% CI 0.83 to 0.96, p=0.004, and OR 0.50, 95% CI 0.34 to 0.73, p=0.0004, respectively). Thirty (21%) of the 141 surviving patients with echocardiographic follow-up recovered LV function at 6 months. Multiple logistic regression analysis revealed that, after adjustment for NYHA functional class, LVEF and left ventricular end diastolic dimension, older age and smaller LVESD at baseline were predictors of LV recovery (OR 1.08, 95% CI 1.01 to 1.17, p=0.02 and OR 0.92, 95% CI 0.86 to 0.98, p=0.007, respectively). CONCLUSIONS: This study suggests that increased LVESD, lower BMI and lower serum cholesterol at baseline may be independent predictors of poor outcome in patients with PPCM, while older age and smaller LVESD at baseline appear to be independently associated with a higher chance of LV recovery.

Long-term outcome of peripartum cardiomyopathy in a population with high seropositivity for human immunodeficiency virus.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a rare cardiomyopathy with a high risk of mortality. The present study assessed clinical outcome and mortality over a 2-year period in an African cohort of 80 PPCM patients. METHODS: A prospective study over a 2-year period at a tertiary center, where 80 consecutive women presenting with PPCM were enrolled on first diagnosis. Patients obtained standard heart failure therapy. Detailed assessments included echocardiography, NYHA functional class, left ventricular ejection fraction (LVEF), mortality and serum levels for hemoglobin, CRP, IL-6, TNF-alpha, Fas/Apo-1, and T-cell count at each 6-month intervals for 24 months. RESULTS: Baseline mean age was 30 ± 7 years; 38% were primigravidas and 34% were co-infected with HIV. NYHA functional class III-IV was present in 89% patients with a mean LVEF of 30 ± 9%. Four patients were lost to follow-up, 9 moved to remote areas, 7 were excluded due to subsequent pregnancy. The 2-year mortality rate was 28%. Eight of 80 (10%) died by 6 months. Mean LVEF of surviving patients was: 44 ± 11% at 6-months, 46 ± 13% at 12-months and 50 ± 14% at 24-months follow-up. Of the 69 patients still enrolled at 6 months 14 (20%) died over the remaining 18-month period, despite functional recovery. No statistically significant difference in LVEF and mortality was observed between PPCM patients with or without HIV co-infection. CONCLUSION: The novel finding of this study is the continuous high mortality of PPCM patients occurring beyond 6 months independent of HIV infection and subsequent pregnancy. This finding strongly encourages the need for long-term clinical follow-up and management of women with PPCM.

Reversal of IFN-gamma, oxLDL and prolactin serum levels correlate with clinical improvement in patients with peripartum cardiomyopathy.

AIM: Peripartum cardiomyopathy (PPCM) is characterized by acute onset of heart failure of unknown aetiology. We aimed to identify mechanisms involved in initiation and progression of the disease. METHODS AND RESULTS: Serum markers related to cardiac function, apoptosis, oxidative stress, remodelling, inflammation and the nursing hormone prolactin were analyzed in PPCM patients and healthy controls. The kinetics of these markers were compared between patients who improved cardiac function (IMP) and those patients who did not improve (NIMP), over 6 months follow-up. All patients received ACE-inhibitors, beta-blockers and diuretics. Baseline levels of TGF-beta-1 were significantly lower, MMP-9 and VEGF were not different; all other markers were significantly higher in PPCM compared with controls. Only baseline NT-proBNP levels were higher in NIMP compared with IMP. After 6 months, NT-proBNP, oxLDL and IFN-gamma were significantly lower in IMP and the decrease in oxLDL, IFN-gamma and prolactin was significant in IMP but not in NIMP. Significant correlations were observed between the kinetics of NT-proBNP, oxLDL, prolactin and IFN-gamma in PPCM patients. CONCLUSION: Baseline NT-proBNP and the failure to decrease oxLDL, IFN-gamma and prolactin are associated with poor outcome in PPCM, suggesting a potential role of these factors in the pathophysiology of PPCM and for risk stratification of PPCM patients.

A cathepsin D-cleaved 16 kDa form of prolactin mediates postpartum cardiomyopathy.

Postpartum cardiomyopathy (PPCM) is a disease of unknown etiology and exposes women to high risk of mortality after delivery. Here, we show that female mice with a cardiomyocyte-specific deletion of stat3 develop PPCM. In these mice, cardiac cathepsin D (CD) expression and activity is enhanced and associated with the generation of a cleaved antiangiogenic and proapoptotic 16 kDa form of the nursing hormone prolactin. Treatment with bromocriptine, an inhibitor of prolactin secretion, prevents the development of PPCM, whereas forced myocardial generation of 16 kDa prolactin impairs the cardiac capillary network and function, thereby recapitulating the cardiac phenotype of PPCM. Myocardial STAT3 protein levels are reduced and serum levels of activated CD and 16 kDa prolactin are elevated in PPCM patients. Thus, a biologically active derivative of the pregnancy hormone prolactin mediates PPCM, implying that inhibition of prolactin release may represent a novel therapeutic strategy for PPCM.

Peripartum cardiomyopathy: inflammatory markers as predictors of outcome in 100 prospectively studied patients.

AIMS: Peripartum cardiomyopathy (PPCM) is a disorder of unknown aetiology with a course and outcome that is largely unpredictable. We evaluated the prognostic role of multiple inflammatory markers in the plasma of a large cohort of African patients with PPCM. METHODS AND RESULTS: The study of 100 patients with newly diagnosed PPCM was single-centred, prospective, and longitudinal. Clinical assessment, echocardiography, and blood analysis were done at baseline and after 6 months of standard therapy. Inflammatory markers were measured at baseline only. Fifteen patients died. Left ventricular ejection fraction (LVEF) improved from 26.2+/-8.2 to 42.9+/-13.6% at 6 months (P<0.0001). However, normalization of LVEF (>50%) was only observed in 23%. Baseline levels of C-reactive protein correlated positively with baseline LV end-diastolic (rs=0.33, P=0.0026) and end-systolic (rs=0.35, P=0.0012) diameters and inversely with LVEF (rs=-0.27, P=0.015). Patients who died presented with significantly lower mean EF and higher Fas/Apo-1 plasma values (P<0.05). Fas/Apo-1 and New York Heart Association functional class (NYHA FC) predicted mortality at baseline. CONCLUSION: Plasma markers of inflammation were significantly elevated and correlated with increased LV dimensions and lower LVEF at presentation. Baseline Fas/Apo-1 and higher NYHA FC were the only predictors of mortality. Normalization of LVEF was only observed in 23% of this African cohort.

Current issues in the diagnosis and management of peripartum cardiomyopathy.

Peripartum cardiomyopathy is a form of heart failure that occurs in women within 1 month pre- and 5 months postdelivery. The syndrome carries a high mortality and predisposing factors are not known. The incidence and prevalence of peripartum cardiomyopathy appear to be increasing and this article aims to alert clinicians to consider a possible diagnosis of peripartum cardiomyopathy, outlines the current treatment options, and describes recent advances in the understanding of the pathophysiology of this condition.

Outcome of subsequent pregnancy in patients with documented peripartum cardiomyopathy.

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 fraction at onset of subsequent pregnancy died 3 months postpartum due to heart failure despite optimal medical therapy. Deterioration of left ventricular function occurred uniformly postpartum and was accompanied by elevation of tumor necrosis factor-alpha 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.