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

ABSTRACT: AIMS:Bromocriptine 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 RESULTS:Consecutive 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 [? 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. CONCLUSIONS:In women newly diagnosed with PPCM, treatment with bromocriptine was independently associated with greater LV functional recovery.

SUBMITTER: Tremblay-Gravel M

PROVIDER: S-EPMC6351886 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

Tremblay-Gravel Maxime M Marquis-Gravel Guillaume G Avram Robert R Desplantie Olivier O Ducharme Anique A Bibas Lior L Pacheco Christine C Couture Etienne E Simard François F Poulin Anthony A Malhamé Isabelle I Tran Dan D Rey Evelyne E Tournoux François F Harvey Luc L Sénéchal Mario M Bélisle Pierre P Descarries Laurence L Farand Paul P Pranno Nicolas N Diaz Ariel A Afilalo Jonathan J Ly Hung Q HQ Fortier Annik A Jolicoeur Etienne Marc EM

ESC heart failure 20181122 1

<h4>Aims</h4>Bromocriptine 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.<h4>Methods and results</h4>Consecutive 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 ...[more]

PMID: 30565890

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Project description:BACKGROUND:Right ventricular (RV) dysfunction predicts adverse outcome in peripartum cardiomyopathy (PPCM). We recently demonstrated beneficial effects associated with the prolactin release inhibitor bromocriptine at different doses when added to standard heart failure therapy in PPCM. Here, we evaluated for the first time the therapeutic potential of bromocriptine particularly in PPCM patients with RV involvement. METHODS:In this study, 40 patients with PPCM were included, of whom 24 patients had reduced RV ejection fraction (RVEF?<?45%). We examined the effect of short-term (1W: bromocriptine, 2.5 mg, 7 days, n?=?10) compared with long-term bromocriptine treatment (8W: 5 mg for 2 weeks followed by 2.5 mg for another 6 weeks, n?=?14) in addition to guideline-based heart failure therapy in patients with an initial RVEF?<?45% on the following outcomes: (1) change from baseline (? delta) in RVEF, (2) change from baseline in left ventricular EF (LVEF), and (3) rate of patients with full LV recovery (LVEF???50%) and (4) rate of patients with full RV recovery (RVEF???55%) at 6-month follow-up as assessed by cardiac magnetic resonance imaging. RESULTS:Reduced RVEF at initial presentation was associated with a lower rate of full cardiac recovery at 6-month follow-up (patients with RV dysfunction: 58% vs. patients with normal RV function: 81%; p?=?0.027). RVEF increased from 38?±?7 to 53?±?11% with a delta-RVEF of +?15?±?12% in the 1W group, and from 35?±?9 to 58?±?7% with a ? RVEF of +?23?±?10% in the 8W group (? RVEF 1W vs 8W: p?=?0.118). LVEF increased from 25?±?8 to 46?±?12% with a ? LVEF of +?21?±?11% in the 1W group, and from 22?±?6 to 49?±?10% with a ? LVEF of +?27?±?9% in the 8W group (? LVEF 1W vs 8W: p?=?0.211). Full LV recovery was present in 50% of the 1W group and in 64% of the 8W group (p?=?0.678). Full RV recovery was observed in 40% of the 1W group and in 79% of the 8W group (p?=?0.092). CONCLUSIONS:Despite overall worse outcome in patients with RV dysfunction at baseline, bromocriptine treatment in PPCM patients with RV involvement was associated with a high rate of full RV and LV recovery, although no significant differences were observed between the short-term and long-term bromocriptine treatment regime. These findings suggest that bromocriptine in addition to standard heart failure therapy may be also effective in PPCM patients with biventricular impairment.

Project description: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.

Project description:Peripartum cardiomyopathy (PPCM) is an idiopathic heart disease that develops in the last month of pregnancy and/or the first months following delivery in previously healthy women and may lead to acute heart failure. A cleaved fragment of the nursing hormone prolactin is considered essential in the pathophysiology of PPCM. To date, no specific therapy has been tested for PPCM in a randomized controlled trial of adequate size.The purpose of this trial is to investigate the safety of the dopamin-D2-receptor agonist bromocriptine and its effects on left ventricular (LV) function in women with PPCM.This is an 11 center German trial with a prospective randomized controlled open-label design. The trial enrolls females with newly diagnosed PPCM according to European Society of Cardiology criteria with a LV ejection fraction (LVEF) <35 %. Patients are randomized 1:1 to either best supportive care (BSC) including standard heart failure therapy plus 8 weeks of bromocriptine therapy (2.5 mg b.i.d. for 14 days and 2.5 mg q.d. from day 15 to 56) or to BSC plus 1 week of low-dose bromocriptine (2.5 mg q.d.) with anticoagulant therapy at a prophylactic dose administered during the period of bromocriptine treatment in both groups. The primary endpoint is change in LVEF from baseline to 6 months follow-up as assessed by cardiac magnetic resonance imaging (or echocardiography if CMR is not tolerated). The secondary endpoints are hospitalization for worsening heart failure, heart transplantation, and all-cause mortality during follow-up or a combination of these endpoints. A total of 60 patients will be recruited (including 6 potential dropouts) giving a power of 0.9 for an expected LVEF change of 10.8 % between treatment groups at 6 months.This trial will provide important knowledge on potential benefits and safety of prolonged inhibition of prolactin release with bromocriptine in addition to standard heart failure therapy in newly diagnosed PPCM.ClinicalTrials.gov Identifier: NCT00998556.

Project description:BackgroundThe term "end stage" has been used to describe hypertrophic cardiomyopathy (HCM) with left ventricular systolic dysfunction (LVSD), defined as occurring when left ventricular ejection fraction is <50%. The prognosis of HCM-LVSD has reportedly been poor, but because of its relative rarity, the natural history remains incompletely characterized.MethodsData from 11 high-volume HCM specialty centers making up the international SHaRe Registry (Sarcomeric Human Cardiomyopathy Registry) were used to describe the natural history of patients with HCM-LVSD. Cox proportional hazards models were used to identify predictors of prognosis and incident development.ResultsFrom a cohort of 6793 patients with HCM, 553 (8%) met the criteria for HCM-LVSD. Overall, 75% of patients with HCM-LVSD experienced clinically relevant events, and 35% met the composite outcome (all-cause death [n=128], cardiac transplantation [n=55], or left ventricular assist device implantation [n=9]). After recognition of HCM-LVSD, the median time to composite outcome was 8.4 years. However, there was substantial individual variation in natural history. Significant predictors of the composite outcome included the presence of multiple pathogenic/likely pathogenic sarcomeric variants (hazard ratio [HR], 5.6 [95% CI, 2.3-13.5]), atrial fibrillation (HR, 2.6 [95% CI, 1.7-3.5]), and left ventricular ejection fraction <35% (HR, 2.0 [95% CI, 1.3-2.8]). The incidence of new HCM-LVSD was ?7.5% over 15 years. Significant predictors of developing incident HCM-LVSD included greater left ventricular cavity size (HR, 1.1 [95% CI, 1.0-1.3] and wall thickness (HR, 1.3 [95% CI, 1.1-1.4]), left ventricular ejection fraction of 50% to 60% (HR, 1.8 [95% CI, 1.2, 2.8]-2.8 [95% CI, 1.8-4.2]) at baseline evaluation, the presence of late gadolinium enhancement on cardiac magnetic resonance imaging (HR, 2.3 [95% CI, 1.0-4.9]), and the presence of a pathogenic/likely pathogenic sarcomeric variant, particularly in thin filament genes (HR, 1.5 [95% CI, 1.0-2.1] and 2.5 [95% CI, 1.2-5.1], respectively).ConclusionsHCM-LVSD affects ?8% of patients with HCM. Although the natural history of HCM-LVSD was variable, 75% of patients experienced adverse events, including 35% experiencing a death equivalent an estimated median time of 8.4 years after developing systolic dysfunction. In addition to clinical features, genetic substrate appears to play a role in both prognosis (multiple sarcomeric variants) and the risk for incident development of HCM-LVSD (thin filament variants).

Dataset Information

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

Publications

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

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