Recovery In Peripartum Cardiomyopathy Research Articles

A novel score to predict left ventricular recovery in peripartum cardiomyopathy derived from the ESC EORP Peripartum Cardiomyopathy Registry.

There are no established clinical tools to predict left ventricular (LV) recovery in women with peripartum cardiomyopathy (PPCM). Using data from women enrolled in the ESC EORP PPCM Registry, the aim was to derive a prognostic model to predict LV recovery at 6 months and develop the 'ESC EORP PPCM Recovery Score'-a tool for clinicians to estimate the probability of LV recovery. From 2012 to 2018, 752 women from 51 countries were enrolled. Eligibility included (i) a peripartum state, (ii) signs or symptoms of heart failure, (iii) LV ejection fraction (LVEF) ≤ 45%, and (iv) exclusion of alternative causes of heart failure. The model was derived using data from participants in the Registry and internally validated using bootstrap methods. The outcome was LV recovery (LVEF ≥50%) at six months. An integer score was created. Overall, 465 women had a 6-month echocardiogram. LV recovery occurred in 216 (46.5%). The final model included baseline LVEF, baseline LV end diastolic diameter, human development index (a summary measure of a country's social and economic development), duration of symptoms, QRS duration and pre-eclampsia. The model was well-calibrated and had good discriminatory ability (C-statistic 0.79, 95% confidence interval [CI] 0.74-0.83). The model was internally validated (optimism-corrected C-statistic 0.78, 95% CI 0.73-0.82). A model which accurately predicts LV recovery at 6 months in women with PPCM was derived. The corresponding ESC EORP PPCM Recovery Score can be easily applied in clinical practice to predict the probability of LV recovery for an individual in order to guide tailored counselling and treatment.

Cabergoline treatment promotes myocardial recovery in peripartum cardiomyopathy.

Peripartum cardiomyopathy (PPCM) is a rare heart disease, occurring in previously heart-healthy women during the last month of pregnancy or the first months after delivery due to left ventricular (LV) systolic dysfunction. A common pathomechanistic pathway of PPCM includes increased oxidative stress and the subsequent generation of a cleaved prolactin fragment (16kDa PRL), which promotes the onset of heart failure (HF) in a microRNA (miR)-146a-dependent manner. Inhibition of prolactin secretion with the dopamine D2 receptor (D2R) agonist bromocriptine combined with standard HF therapy supports cardiac recovery. This study examined whether treatment with the more selective D2R agonist cabergoline prevents HF development in an experimental PPCM mouse model and might be used as an alternative treatment regime for PPCM. Postpartum (PP) female PPCM-prone mice with a cardiomyocyte restricted STAT3-deficiency (αMHC-Cretg/+ ; Stat3fl/fl ; CKO) were treated over two consecutive nursing periods with cabergoline (CKO Cab, 0.5mg/kg/day) and were compared with bromocriptine treated CKO (CKO Br) and postpartum-matched WT and CKO mice. Cabergoline treatment in CKO PP mice preserved cardiac function [fractional shortening (FS): CKO Cab: 34.5±9.4% vs. CKO: 22.1±9%, P<0.05] and prevented the development of cardiac hypertrophy, fibrosis, and inflammation as effective as bromocriptine therapy (FS: CKO Br: 33.4±5.6%). The myocardial up-regulation of the PPCM biomarkers plasminogen inhibitor activator 1 (PAI-1) and miR-146a were prevented by both cabergoline and bromocriptine therapy. A small cohort of three PPCM patients from the German PPCM Registry was treated with cabergoline (1mg per week for 2weeks, followed by 0.5mg per week for another 6weeks) due to a temporary unavailability of bromocriptine. All PPCM patients initially presented with a severely reduced LV ejection fraction (LVEF: 26±2%). However, at 6months of follow-up, LV function (LVEF: 56±2%) fully recovered in all three PPCM patients, and no adverse events were detected. In the experimental PPCM mouse model, the selective D2R agonist cabergoline prevents the onset of postpartum HF similar to bromocriptine. In PPCM patients, cabergoline treatment was safe and effective as all patients fully recovered. Cabergoline might serve as a promising alternative to bromocriptine. However, these findings are based on experimental data and a small case series and thus have to be interpreted with caution and should be validated in a larger clinical trial.

NT-proBNP and predictors of event free survival and left ventricular systolic function recovery in peripartum cardiomyopathy

ObjectiveTo determine predictors of adverse outcomes in peripartum cardiomyopathy (PPCM). Methods and resultsWe conducted a multi-center cohort study across four centers to identify subjects with PPCM with the following criteria: LVEF <40%, development of heart failure within the last month of pregnancy or within 5 months of delivery and no other identifiable cause of heart failure with reduced ejection fraction. Outcomes included 1) survival free from major adverse events (need for extra-corporeal membrane oxygenation, ventricular assist device, orthotopic heart transplantation or death) and 2) LVEF recovery ≥ 50%. Using a univariate logistic regression analysis, we identified significant clinical predictors of these outcomes, which were then used to create multivariable models. NT-proBNP at the time of diagnosis was examined both as a continuous variable (log transformed) in logistic regression and as a dichotomous variable (values above and below the median) using the log-rank test.In all, 237 women (1993 to 2017) with 736.4 person-years of follow-up, met criteria for PPCM. Participants had a mean age of 32.4 ± 6.7 years, mean BMI 30.6 ± 7.8 kg/m2; 63% were White. After median follow-up of 3.6 years (IQR 1.1–7.8), 113 (67%) had LVEF recovery, and 222 (94%) had survival free from adverse events. Significant predictors included gestational age, gravidity, systolic blood pressure, smoking, heart rate, initial LVEF, and diuretic use. In a subset of 110 patients with measured NTproBNP levels, we found a higher event free survival for women with NTproBNP <2585 pg/ml (median) as compared to women with NTproBNP ≥2585 pg/ml (log-rank test p-value 0.018). ConclusionGestational age, gravidity, current or past tobacco use, systolic blood pressure, heart rate, initial LVEF and diuretic requirement at the time of diagnosis were associated with survival free from adverse events and LVEF recovery. Initial NT-proBNP was significantly associated with event free survival.

Taurine as an adjunct therapy for early left ventricular recovery in peripartum cardiomyopathy

Background and Aims: The pathophysiology of peripartum cardiomyopathy is not fully understood. Despite standard medical therapy, both morbidity and mortality remain high. Restoration of inflammatory cytokine balance may hold promise for therapy. Taurine has a powerful immune-modulatory and anti-inflammatory in addition to positive inotropic effect. This study evaluates the effect of taurine infusion on clinical status, left ventricular function, circulating plasma levels of N-terminal brain natriuretic peptide and C-reactive protein in women with peripartum cardiomyopathy. Methods: Forty women with peripartum cardiomyopathy admitted postpartum to the ICU were randomly assigned to one of two groups (20 in each group): Group T received taurine infusion and Group C received normal saline infusion over 24 hours for 5 days. Both groups received standard heart failure therapy according the institutional treatment protocol. Results: In the taurine group on day 5, there was a significant reduction in LVEDD and LVESD and significant increase in LVEF. All patients had an improvement in LVEF of at least 10% and 5 patients had recovery of LVEF to ≥50% on day 5 while the other 15 patients had LVEF 45- 50%. In the control group on day 5, there was non-significant change in LVEDD, LVESD and LVEF and no patient had recovery of LVEF to ≥50% or showed improvement in LVEF more than 10%. NYHA functional class showed significant increase on day 5 in the taurine group compared to the control group. Seventeen patients (85%) in the taurine group showed improvement of the NYHA functional class at day 5. In contrast, only 2 patients (10%) in the control group showed improvement of NYHA functional class at day 5. Conclusion: Early addition of taurine infusion to standard heart failure therapy improves both; echocardiographic parameters and laboratory parameters but without clinically significant changes in women with peripartum cardiomyopathy.

Prognostic value of NT-pro-BNP for myocardial recovery in peripartum cardiomyopathy

Abstract Background Peripartum cardiomyopathy (PPCM) is an important cause of pregnancy-associated heart failure and occurs in women towards the end of pregnancy or within the first five months post-partum. Though PPCM is mostly associated with left ventricular (LV) recovery, many affected women develop chronic heart failure with persistently reduced LV ejection fraction (LVEF). Despite recent advances in the treatment of PPCM, clinical predictors of myocardial recovery remain sparse. Purpose N-terminal pro-brain natriuretic peptide (NT-pro-BNP) is the only clinically established biomarker with diagnostic value in PPCM. However, its prognostic value for LV recovery in PPCM remains uncertain. We aimed to establish whether NT-pro-BNP could serve as a predictor of LV recovery in PPCM, and if so, which levels would help with such risk stratification. Methods Women with PPCM seen at the Cardiomyopathy Clinic at Groote Schuur Hospital were recruited between 2012 and 2018. Clinical details and echocardiographic features were recorded at baseline and follow-up, and NT-pro-BNP was measured at baseline. LV recovery was defined as an LVEF of ≥50% at 12-month follow-up. Results This cohort of 42 women with PPCM had a mean age of 29.3±5.8 years and median parity of 2 (IQR 1–4). Almost half (45.2%) presented with a NYHA functional class III/IV. The median systolic and diastolic blood pressures were 117mmHg (IQR 105–133) and 75mmHg (IQR 68–85) respectively. The median heart was 94bpm (IQR 74–103). At diagnosis, mean LVEF was 31.1±8.4% and LV end-diastolic dimension (EDD) of 59mm (IQR 53–64), which improved to LVEF 44.5%±14.5 (p=0.001) and LVEDD 53.6mm (p=0.007) at 1 year. Median NT-pro-BNP at presentation was 915.8pg/mL (IQR 613.6–2422.5). Patients presenting with sinus tachycardia (heart rate &amp;gt;100 bpm) had significantly higher NT-pro-BNP values (1815 vs. 728pg/mL, p=0.009) at the time of diagnosis. At presentation, NT-pro-BNP tended to correlate with LVEDD (R 0.33, p=0.04) and was inversely correlated with LVEF (R −0.39, p=0.01). Whereas initial LVEDD and LVEF did not predict LV recovery at 1 year, NT-pro-BNP at the time of diagnosis had prognostic significance. Patients without LV recovery had a significantly higher NT-pro-BNP at diagnosis (1694.1pg/mL vs. 613.1pg/mL, p=0.02). As shown in Figure 1, NT-pro-BNP of &amp;gt;900pg/mL was associated with lower probability of LV recovery (OR 0.19 [95% CI 0.05–0.73], p=0.018). Conclusion We show, for the first time, that NT-pro-BNP has a prognostic value for LV recovery in PPCM. NT-pro-BNP may be useful in the risk stratification in PPCM and may be used to recommend more intensive follow-up of patients who have a NT-pro-BNP &amp;gt;900pg/mL at diagnosis. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study was supported by the South African Medical Research Council and National Research Foundation of South Africa.

Left ventricular function recovery in peripartum cardiomyopathy: a cardiovascular magnetic resonance study by myocardial T1 and T2 mapping

BackgroundPeripartum cardiomyopathy (PPCM) is rare and potentially life-threatening; its etiology remains unclear. Imaging characteristics on cardiovascular magnetic resonance (CMR) and their prognostic significance have rarely been studied. We sought to determine CMR’s prognostic value in PPCM by using T1 and T2 mapping techniques.MethodsData from 21 PPCM patients from our CMR registry database were analyzed. The control group comprised 20 healthy age-matched females. All subjects underwent comprehensive contrast-enhanced CMR. T1 and T2 mapping using modified Look-Locker inversion recovery and T2 prep balanced steady-state free precession sequences, respectively. Ventricular size and function, late gadolinium enhancement (LGE), myocardial T1 value, extracellular volume (ECV), and T2 value were analyzed. Transthoracic echocardiography was performed at baseline and during follow-up. The recovered left ventricular ejection fraction (LVEF) was defined as LVEF ≥50% on echocardiography follow-up after at least 6 months of the diagnosis.ResultsCMR imaging showed that the PPCM patients had severely impaired LVEF and right ventricular ejection fraction (LVEF: 26.8 ± 10.6%; RVEF: 33.9 ± 14.6%). LGE was seen in eight (38.1%) cases. PPCM patients had significantly higher native T1 and ECV (1345 ± 79 vs. 1212 ± 32 ms, P < 0.001; 33.9 ± 5.2% vs. 27.1 ± 3.1%, P < 0.001; respectively) and higher myocardial T2 value (42.3 ± 3.7 vs. 36.8 ± 2.3 ms, P < 0.001) than did the normal controls. After a median 2.5-year follow-up (range: 8 months-5 years), six patients required readmission for heart failure, two died, and 10 showed left ventricular function recovery. The LVEF-recovered group showed significantly lower ECV (30.7 ± 2.1% vs. 36.8 ± 5.6%, P = 0.005) and T2 (40.6 ± 3.0 vs. 43.9 ± 3.7 ms, P = 0.040) than the unrecovered group. Multivariable logistic regression analysis showed ECV (OR = 0.58 for per 1% increase, P = 0.032) was independently associated with left ventricular recovery in PPCM.ConclusionsCompared to normal controls, PPCM patients showed significantly higher native T1, ECV, and T2. Native T1, ECV, and T2 were associated with LVEF recovery in PPCM. Furthermore, ECV could independently predict left ventricular function recovery in PPCM.

Influence of Hypertensive Disorders of Pregnancy on Phenotype and Recovery in Peripartum Cardiomyopathy [27L

INTRODUCTION: Peripartum cardiomyopathy (PPCM) and cardiomyopathy secondary to hypertensive disorders of pregnancy (HDP) are considered to represent distinct cardiac entities (i.e. dilated vs hypertrophic cardiomyopathy). The goal of this systematic review and meta-analysis was to determine if HDP alters the odds of recovery and if baseline left ventricle characteristics are significantly different. METHODS: Ovid Medline, EMBASE, CENTRAL and Scopus were searched for combinations of the following: hypertension, preeclampsia, cardiomyopathy, peripartum, postpartum or puerperium. Articles describing initial left ventricular ejection fraction (LVEF), odds of recovery (EF &gt;50%) or end diastolic diameter (EDD) amongst those with PPCM were included. Two raters analyzed abstracts and full text to determine eligibility and risk of bias. Risk of bias was determined using the Newcastle-Ottawa scale and the DerSimonian-Laird method was used to combine odds ratios. RESULTS: 1838 articles were identified and 148 full text articles were reviewed for eligibility, with 11 observational studies meeting criteria. There was substantial agreement for selection (K: 0.817) and for risk of bias (K: 0.633) between raters. There was no significant difference (mean: 1.837%, 95% CI-4.882, 1.282) in baseline LVEF or EDD (1.837 cm, 95% CI-1.104, 4.778) between patients who developed PPCM +/- HDP. Further, recovery rates between groups were similar with OR of 1.870 (95% CI 0.854, 4.094) and a moderate degree of heterogeneity. CONCLUSION: Counseling regarding eventual recovery of LVEF after PPCM should not be altered due to the presence of HDP; it is unlikely that a phenotypic difference exists in the cardiomyopathy induced by HDP compared to idiopathic PPCM.

PREVALENCE AND PREDICTORS OF MYOCARDIAL RECOVERY IN PERIPARTUM CARDIOMYOPATHY: A SYSTEMATIC REVIEW

Although peripartum cardiomyopathy (PPCM) is associated with mortality and morbidity, improvement in cardiac function – termed myocardial recovery – can occur. No study has systematically reviewed myocardial recovery in PPCM and its independent predictors. A systematic review was performed of

The effect of bromocriptine on left ventricular functional recovery in peripartum cardiomyopathy: insights from the BRO-HF retrospective cohort study.

AimsBromocriptine is thought to facilitate left ventricular (LV) recovery in peripartum cardiomyopathy (PPCM) through inhibition of prolactin secretion. However, this potential therapeutic effect remains controversial and was incompletely studied in diverse populations.Methods and resultsConsecutive women with new‐onset PPCM (n = 76) between 1994 and 2015 in Quebec, Canada, were classified according to treatment (n = 8, 11%) vs. no treatment (n = 68, 89%) with bromocriptine. We assessed LV functional recovery at mid‐term (6 months) and long‐term (last follow‐up) and compared outcomes among groups. Women treated with bromocriptine experienced better mid‐term left ventricular ejection fraction (LVEF) recovery from 23 ± 10% at baseline to 55 ± 12% at 6 months, compared with a change from 30 ± 12% at baseline to 45 ± 13% at 6 months in women treated with standard medical therapy (P interaction < 0.01). At long‐term, a similar positive association was found with bromocriptine (9% greater LVEF variation, P interaction < 0.01). In linear regressions adjusted for obstetrical, clinical, echocardiographic, and pharmacological variables, treatment with bromocriptine was associated with a greater improvement in LVEF [β coefficient (standard error), 14.1 (4.4); P = 0.03]. However, there was no significant association between bromocriptine use and the combined occurrence of all‐cause death and heart failure events (hazard ratio, 1.18; 95% confidence interval, 0.15 to 9.31), using univariable Cox regressions based over a cumulative follow‐up period of 285 patient‐years.ConclusionsIn women newly diagnosed with PPCM, treatment with bromocriptine was independently associated with greater LV functional recovery.

Predictors of early and delayed recovery in peripartum cardiomyopathy: a prospective study of 52 Patients

Background: Predictors of early or delayed recovery are unclear in peripartum cardiomyopathy (PPCM). Therefore, we aimed to assess the prognostic value of serial assessment of clinical, echocardiographic, and biochemical markers in patients with PPCM.Methods: Fifty-two consecutive women with PPCM were enrolled in this prospective study. Each patient underwent transthoracic echocardiography, B-type natriuretic peptide (BNP) and C-reactive protein (CRP) measurement at admission, and every 3 months. Early recovery was defined as resolution of heart failure at 6 months postdiagnosis, delayed recovery was defined if the length of time required for recovery of left ventricular function was longer than 6 months, and persistent left ventricular dysfunction (PLVD) was defined as an ejection fraction of less than 50% at the end of follow-up.Results: Thirty patients (57.7%) recovered completely, 10 died (19.2%), and 12 (23.1%) had PLVD. There were no significant differences in baseline BNP and CRP values between patients who recovered completely and who did not recover. However, patients with complete recovery were more likely to have a higher left ventricular ejection fraction, smaller left ventricle end-systolic dimensions at baseline, and lower CRP and BNP levels at follow-up. Elevated levels of BNP and CRP on follow up at 3 and 6 months were associated with nonrecovery. Third and sixth month BNP values were significantly lower in patients with rapid recovery, compared to patients with delayed recovery. Bromocriptine therapy was also associated with early recovery.Conclusions: Persistent elevation of plasma CRP and BNP levels at follow-up portend a slower response or nonrecovery in patients with PPCM. Bromocriptine therapy was an independent predictor of early recovery.

IMPACT OF DIABETES ON MYOCARDIAL RECOVERY IN WOMEN WITH PERIPARTUM CARDIOMYOPATHY

Peripartum cardiomyopathy (PPCM) remains a major cause of maternal morbidity and mortality. Previous studies have proposed vascular toxicity and hormonal dysfunction as contributing to the etiology of PPCM. We examined the impact of the diabetes on myocardial recovery in PPCM. 100 women with PPCM

GNB3 C825T Polymorphism and Myocardial Recovery in Peripartum Cardiomyopathy: Results of the Multicenter Investigations of Pregnancy-Associated Cardiomyopathy Study.

Black women are at greater risk for peripartum cardiomyopathy (PPCM). The guanine nucleotide-binding proteins β-3 subunit (GNB3) has a polymorphism C825T. The GNB3 TT genotype more prevalent in blacks is associated with poorer outcomes. We evaluated GNB3 genotype and myocardial recovery in PPCM. A total of 97 women with PPCM were enrolled and genotyped for the GNB3 T/C polymorphism. Left ventricular ejection fraction (LVEF) was assessed by echocardiography at entry, 6 and 12 months postpartum. LVEF over time in subjects with the GNB3 TT genotype was compared with those with the C allele overall and in black and white subsets. The cohort was 30% black, age 30+6, LVEF 0.34+0.10 at entry 31+25 days postpartum. The % GNB3 genotype for TT/CT/CC=23/41/36 and differed markedly by race (blacks=52/38/10 versus whites=10/44/46, P<0.001). In subjects with the TT genotype, LVEF at entry was lower (TT=0.31+0.09; CT+CC=0.35+0.09, P=0.054) and this difference increased at 6 (TT=0.45+0.15; CT+CC=0.53+0.08, P=0.002) and 12 months (TT=0.45+0.15; CT+CC=0.56+0.07, P<0.001.). The difference in LVEF at 12 months by genotype was most pronounced in blacks (12 months LVEF for GNB3 TT=0.39+0.16; versus CT+CC=0.53+0.09, P=0.02) but evident in whites (TT=0.50++0.11; CT+CC=0.56+0.06, P=0.04). The GNB3 TT genotype was associated with lower LVEF at 6 and 12 months in women with PPCM, and this was particularly evident in blacks. Racial differences in the prevalence and impact of GNB3 TT may contribute to poorer outcomes in black women with PPCM.

Abstract 18911: Relaxin-2 Levels and Early Myocardial Recovery in Peripartum Cardiomyopathy: Results of the Multicenter IPAC Study

Introduction: Relaxin-2 is a polypeptide hormone which is elevated in peripartum women. Recombinant relaxin-2 is under investigation as a therapy for acute heart failure. Whether endogenous relaxin influences myocardial function in peripartum cardiomyopathy (PPCM) has not been previously investigated. We investigated the impact of relaxin-2 on recovery in PPCM in the multicenter Investigations of Pregnacy Associated Cardiomyopathy (IPAC) study. Methods: 98 women with PPCM were enrolled and serum obtained at entry. LVEF was assessed by echocardiography at entry, 2 months, 6 months and 12 months. Relaxin-2 levels were measured by ELISA. Myocardial recovery was evaluated by tertiles of relaxin at entry for the entire cohort (n=98). Given that relaxin-2 levels were most elevated early, we then reevaluated the impact of relaxin specifically in subjects enrolled in the first quartile based on days postpartum to entry. Results: Overall the cohort was 30% black 65% white and 5% other. Mean age was 30 + 6 years, LVEF 0.35 + 0.10 and time to entry 31 + 25 days post-partum. The mean relaxin level was 29 + 110 pg/ml and dropped rapidly postpartum (correlation r= -0.42, p&lt;0.001, mean relaxin2 for post postpartum quartiles=97 + 203 (0 to 11 days), 10 + 31 (12 to 24), 4 + 2(25 to 51), 5 + 7 (51 to 95),p=0.004. For relaxin tertiles analysis for the overall cohort, subjects with the highest levels at entry had the highest mean LVEF at 2 months postpartum, (LVEF high/intermediate/low relaxin= 0.47 + 0.10/0.44 + 0.10/0.39 + 0.10,p=0.01). When reevaluated only in women presenting in the first quartile( n=25, days postpartum 6.5 +3.2 , range 0 -11 days), LVEF at 2 months was again higher in those with the highest relaxin levels (relaxin tertiles high/intermediate/low =0.53 + 0.10/ 0.45 + 0.09/0.38 + 0.11, p=0.02) with a trend at 6 months (p=0.09) and 12 months(12 month LVEF tertiles=0.55 + 0.08/ 0.53 + 0.09/0.47 + 0.14, p=0.19). Conclusions: In women with PPCM, higher relaxin-2 levels were associated with early myocardial recovery and higher LVEF at 2 months.Endogenous relaxin appears play a cardio protective role in PPCM. The role of treatment with recombinant relaxin to facilitate myocardial recovery in PPCM remains to be determined.

Abstract 18749: Body Mass Index, Leptin, and Recovery in Peripartum Cardiomyopathy: Results of the Multicenter IPAC Study

Introduction: The contribution of obesity and metabolic syndrome to the development of peripartum cardiomyopathy (PPCM) remains unknown. Leptin is a peptide hormone released by adipose tissue which may mediate impact of the obesity on cardiovascular function. We sought to evaluate their effect on myocardial recovery in PPCM in the multicenter Investigation of Pregnancy Associated Cardiomyopathy (IPAC) study. Methods: 100 women with new onset of PPCM were enrolled and serum obtained for biomarker analysis at entry. Myocardial function was assessed by echocardiography at entry, 2 months, 6 months and 12 months postpartum and LVEF calculated at a core lab. Leptin levels were measured by ELISA and the correlation of leptin with body mass index (BMI) and days post-partum evaluated. LVEF over the first year postpartum was compared by BMI at study entry (BMI &gt;30 versus&lt;=) and then compared by of Leptin levels (median). Results: The cohort was 30% black 65% white 5% other,age 30 + 6, mean BMI was 28.9 + 7.4 and LVEF 0.34 + 0.10 at study entry 31 + 25 days post-partum.Compared to those with a BMI&lt;=30 women with a BMI &gt; 30 had a similar LVEF at entry (LVEF BMI&gt;30 vs &lt; : 0.35 + 0.09 vs 0.34 + 0.10, p=0.60), but a lower LVEF at 2 month (0.39 + 0.12 vs 0.45 + 0.12, p=0.02), 6months (0.38 + 0.12 vs 0.53 + 0.09, p=0.02) and 12 months (0.50 + 0.13 vs 0.55 + 0.08, p=0.03). Leptin levels (mean 23.4 + 21.1 ng/ml, median 15.26 ng/ml) correlated with BMI (r=0.57, p&lt;0.001). Higher leptin levels were associated with more remodeling (LVEDD for high/low leptin= 5.8 + 0.7/5.4 + 0.6, p=0.02) at entry and lower LVEF 2months (high/low= 0.40 + 0.12/ 0.46 + 0.11, p=0.02) which persisted at 12 months (high/low= 0.51 + 0.11/0.56 + 0.08, p=0.03). Leptin levels were significantly lower at entry in subjects who subsequently recovered to an LVEF&gt;=0.50 (19.2 + 19.1 vs 31.8 + 22.9, p=0.006), and were higher in diabetics (p=0.01) and in blacks (p=0.03). Conclusions: In women with PPCM, obesity was associated with a lower LVEF at 6 and 12 months. Leptin levels correlated with BMI and were associated with greater LV remodeling at presentation and lower LVEF at 12 months. The impact of obesity and leptin on the development of cardiomyopathy warrants further investigation.

Abstract 18476: Myocardial Recovery in Peripartum Cardiomyopathy: Effect of the GNB3 C825T Polymorphism in the Multicenter IPAC study

Background: Peripartum cardiomyopathy (PPCM) remains a major cause of maternal morbidity and mortality. Black race is a risk factor for the disorder and although most women recover myocardial function, previous studies suggest less recovery in black women than in whites. The genetic basis of this racial difference in risk and recovery remains unknown. A polymorphism of a G protein beta subunit (GNB3 C825T) in exon 10 has been studied extensively for a potential role in increased risk of hypertension in blacks. We investigated the impact of the GNB3 C825T polymorphism on myocardial recovery in PPCM in the multicenter IPAC study (Investigation of Pregnancy Associated Cardiomyopathy). Method: 97 women with new onset of PPCM were enrolled and genotyped for the GNB3 T/C polymorphism. Myocardial function was assessed by echocardiography at study entry, 2, 6 and 12 months postpartum and LVEF calculated at a core lab. Myocardial recovery in subjects with the GNB3TT genotype was compared to subjects with the GNB3 C allele (CC and CT combined) first for the overall cohort then separately in black and white subsets. Results: Overall the cohort was 30% black, mean age 30 + 6, and LVEF 0.35 + 0.10 at study entry 31 + 25days post-partum. For the overall cohort, the % GNB3 genotype TT/CT/CC =23/41/36 and differed markedly by Race (Black= 52/38/10 versus Whites=10/43/47, p&lt;0.001). In subjects with the GNB3TT genotype, LVEF was similar early postpartum (TT= 0.35 + 0.07; CT+CC= 0.35 + 0.09, p=0.98) but significantly lower at 2 month (TT=0.38 + 0.15; CT+CC= 0.44 + 0.10, p=0.02), 6 months (TT=0.45 + 0.15; CT+CC= 0.53 + 0.08, p=0.002), and 12 months (TT=0.45 + 0.15; CT+CC= 0.56 + 0.07, p&lt;0.001.). The difference in recovery for GNB3 TT subjects was most pronounced in black women (12 months LVEF for GNB3 TT=0.39 + 0.16; versus CT+CC= 0.53 + 0.09, p=0.02) but was still evident in whites ((TT=0.50 + 0.11; CT+CC= 0.56 + 0.06, p=0.04). Conclusion: In IPAC, Women with the GNB3 TT genotype had significantly less myocardial recovery over the first year post-partum, and its impact was particularly evident in black women. The increase prevalence of the GNB3 TT genotype in blacks may contribute to racial differences in myocardial recovery in women with PPCM

Late recovery in peripartum cardiomyopathy

Late recovery in peripartum cardiomyopathy

Delayed myocardial recovery in peripartum cardiomyopathy

Peripartum cardiomyopathy (PPCM) is an enigmatic cause of heart failure (HF) that occurs during the peripartum period. The global incidence of PPCM varies widely, with the highest rates in countries such as Nigeria, intermediate rates in South Africa and the lowest rates in the most developed regions of the world such as the United States. In the United States, the mean incidence rate is 3.1 per 10,000 live births [1] with the highest incidence and prevalence of PPCM among Blacks, followed by Hispanics and Whites, respectively [2,3].

Delayed recovery in peripartum cardiomyopathy: an indication for long‐term follow‐up and sustained therapy

Persistence of left ventricular (LV) systolic dysfunction after 6 months of diagnosis is believed to be a marker of an irreversible cardiomyopathy in peripartum cardiomyopathy (PPCM). We sought to determine the length of time required for recovery of LV systolic function (LVSF) in patients with PPCM. Forty-two consecutive women with PPCM were enrolled in this prospective study. The minimum required time of follow-up for inclusion was 30 months. Each patient underwent transthoracic echocardiography, and plasma brain natriuretic peptide (BNP) and C-reactive protein measurement at admission, and every 3 months. Early recovery was defined as normalization of LVSF at 6 months post-diagnosis. Delayed recovery was defined if the length of time required for recovery of LVSF was longer than 6 months. Persistent left ventricular dysfunction (PLVD) was defined as an ejection fraction of <50% at the end of follow-up. Twenty patients (47.6%) recovered completely, 10 died (23.8%), and 12 (28.6%) had PLVD. Average time to complete recovery was 19.3 months after initial diagnosis (3-42 months). Early recovery was observed only in six patients (30%), whereas delayed recovery was observed in 14 out of 20 patients (70%). Patients with complete recovery were more likely to have a higher LV ejection fraction and smaller LV end-systolic dimensions at baseline. Full recovery of LVSF in PPCM patients often requires longer than 6 months.

Myocardial recovery in peri-partum cardiomyopathy after continuous flow left ventricular assist device

Left ventricular assist devices (LVADs) offer effective therapy for severe heart failure (HF) as bridge to transplantation or destination therapy. Rarely, the sustained unloading provided by the LVAD has led to cardiac reverse remodelling and recovery, permitting explantation of the device. We describe the clinical course of a patient with severe peri-partum cardiomyopathy (PPCM) rescued with a continuous flow LVAD, who experienced recovery and explantation. We discuss assessment of and criteria for recovery.

Myocardial Recovery in Peripartum Cardiomyopathy: Prospective Comparison With Recent Onset Cardiomyopathy in Men and Nonperipartum Women

BackgroundWhether myocardial recovery occurs more frequently in peripartum cardiomyopathy (PPCM) than in recent onset cardiomyopathies in men and nonperipartum women has not been prospectively evaluated. This was examined through an analysis of outcomes in the Intervention in Myocarditis and Acute Cardiomyopathy 2 (IMAC2) registry. Methods and ResultsIMAC2 enrolled 373 subjects with recent onset nonischemic dilated cardiomyopathy. Left ventricular ejection fraction (LVEF) was assessed at entry and 6 months, and subjects followed for up to 4 years. Myocardial recovery was compared between men (group 1), nonperipartum women (group 2) and subjects with PPCM (group 3). The cohort included 230 subjects in group 1, 104 in group 2, and 39 in group 3. The mean LVEF at baseline in groups 1, 2, and 3 was 0.23 ± 0.08, 0.24 ± 0.08, and 0.27 ± 0.07 (P = .04), and at 6 months was 0.39 ± 0.12, 0.42 ± 0.11, and 0.45 ± 0.14 (P = .007). Subjects in group 3 had a much greater likelihood of achieving an LVEF >0.50 at 6 months than groups 1 or 2 (19 %, 34%, and 48% respectively, P = .002). ConclusionsProspective evaluation confirms myocardial recovery is greatest in women with PPCM, poorest in men, and intermediate in nonperipartum women. On contemporary therapy, nearly half of women with PPCM normalize cardiac function by 6 months.