Prognostic value of NT-proBNP for myocardial recovery in peripartum cardiomyopathy (PPCM)

Introduction Peripartum cardiomyopathy (PPCM) is an important cause of pregnancy-associated heart failure worldwide. Although a significant number of women recover their left ventricular (LV) function within 12 months, some remain with persistently reduced systolic function. Methods Knowledge gaps exist on predictors of myocardial recovery in PPCM. N-terminal pro-brain natriuretic peptide (NT-proBNP) is the only clinically established biomarker with diagnostic value in PPCM. We aimed to establish whether NT-proBNP could serve as a predictor of LV recovery in PPCM, as measured by LV end-diastolic volume (LVEDD) and LV ejection fraction (LVEF). Results This study of 35 women with PPCM (mean age 30.0 ± 5.9 years) had a median NT-proBNP of 834.7 pg/ml (IQR 571.2–1840.5) at baseline. Within the first year of follow-up, 51.4% of the cohort recovered their LV dimensions (LVEDD  50%). Women without LV recovery presented with higher NT-proBNP at baseline. Multivariable regression analyses demonstrated that NT-proBNP of ≥ 900 pg/ml at the time of diagnosis was predictive of failure to recover LVEDD (OR 0.22, 95% CI 0.05–0.95, P = 0.043) or LVEF (OR 0.20 [95% CI 0.04–0.89], p = 0.035) at follow-up. Conclusions We have demonstrated that NT-proBNP has a prognostic value in predicting LV recovery of patients with PPCM. Patients with NT-proBNP of ≥ 900 pg/ml were less likely to show any improvement in LVEF or LVEDD. Our findings have implications for clinical practice as patients with higher NT-proBNP might require more aggressive therapy and more intensive follow-up. Point-of-care NT-proBNP for diagnosis and risk stratification warrants further investigation

Effect of eplerenone on extracellular cardiac matrix biomarkers in patients with acute ST-elevation myocardial infarction without heart failure: insights from the randomized double-blind REMINDER Study

Objective: Aldosterone stimulates cardiac collagen synthesis. Circulating biomarkers of collagen turnover provide a useful tool for the assessment of cardiac remodeling in patients with an acute myocardial infarction (MI).  Methods: The REMINDER trial assessed the effect of eplerenone in patients with an acute ST-elevation Myocardial Infarction (STEMI) without known heart failure (HF), when initiated within 24 h of symptom onset. The primary outcome was almost totally (>90%) driven by natriuretic peptide (NP) thresholds after 1-month post-MI (it also included a composite of cardiovascular death or re-hospitalization or new onset HF or sustained ventricular tachycardia or fibrillation or LVEF ≤40% after 1-month post-MI). This secondary analysis aims to assess the extracellular matrix marker (ECMM) levels with regards to: (1) patients` characteristics; (2) determinants; (3) and eplerenone effect.  Results: Serum levels of ECMM were measured in 526 (52%) of the 1012 patients enrolled in the REMINDER trial. Patients with procollagen type III N-terminal propeptide (PIIINP) above the median were older and had worse renal function (p < 0.05). Worse renal function was associated with increased levels of PIIINP (standardized β ≈ 0.20, p < 0.05). Eplerenone reduced PIIINP when the levels of this biomarker were above the median of 3.9 ng/mL (0.13 ± 1.48 vs. -0.37 ± 1.56 ng/mL, p = 0.008). Higher levels of PIIINP were independently associated with higher proportion of NP above the prespecified thresholds (HR = 1.95, 95% CI 1.16-3.29, p = 0.012).  Conclusions: Eplerenone effectively reduces PIIINP levels when baseline values were above the median. Eplerenone may limit ECMM formation in post-MI without HF

Haemorrhage and other complications in pregnant women on anticoagulation for mechanical heart valves: a prospective observational cohort study

Objective: To document maternal and foetal morbidity and mortality in anticoagulated, pregnant patients with mechanical heart valves until 42 days postpartum. Methods: In a tertiary single-centre, prospective cohort, 178 consecutive patients at the cardiac-obstetric clinic were screened for warfarin use between 1 July 2010 and 31 December 2015. Of 33 pregnancies identified, 29 were included. Patients received intravenous unfractionated heparin from six to 12 weeks' gestation and peripartum, and warfarin from 12 to 36 weeks. Maternal outcomes including death, major haemorrhage and thrombosis, and foetal outcomes were documented. Results: There were two maternal deaths, five returns to theatre post-delivery, eight patients transfused, six major haemorrhages, one case of infective endocarditis and three ischaemic strokes. Ten pregnancies had poor foetal outcomes (six miscarriages, three terminations, one early neonatal death). Twenty patients required more than 30 days' hospitalisation, and 15 required three or more admissions. HIV positivity was associated with surgical delivery (p = 0.0017). Conclusion: Complication rates were high despite centralised care

FHL1B Interacts with lamin A/C and emerin at the nuclear lamina and is misregulated in Emery-Dreifuss Muscular Dystrophy

BACKGROUND: Emery-Dreifuss muscular dystrophy (EDMD) is associated with mutations in EMD and LMNA genes, encoding for the nuclear envelope proteins emerin and lamin A/C, indicating that EDMD is a nuclear envelope disease. We recently reported mutations in FHL1 gene in X-linked EDMD. FHL1 encodes FHL1A, and the two minor isoforms FHL1B and FHL1C. So far, none have been described at the nuclear envelope. OBJECTIVE: To gain insight into the pathophysiology of EDMD, we focused our attention on the poorly characterized FHL1B isoform. METHODS: The amount and the localisation of FHL1B were evaluated in control and diseased human primary myoblasts using immunofluorescence and western blotting. RESULTS: We found that in addition to a cytoplasmic localization, this isoform strongly accumulated at the nuclear envelope of primary human myoblasts, like but independently of lamin A/C and emerin. During myoblast differentiation, we observed a major reduction of FHL1B protein expression, especially in the nucleus. Interestingly, we found elevated FHL1B expression level in myoblasts from an FHL1-related EDMD patient where the FHL1 mutation only affects FHL1A, as well as in myoblasts from an LMNA-related EDMD patient. CONCLUSIONS: Altogether, the specific localization of FHL1B and its modulation in disease-patient's myoblasts confirmed FHL1-related EDMD as a nuclear envelope disease

Relationship Between Galectin-3 Levels and Mineralocorticoid Receptor Antagonist Use in Heart Failure: Analysis From HF-ACTION

BACKGROUND: Galectin-3 (Gal-3) is a marker of myocardial fibrosis, and elevated levels are associated with adverse outcomes. Mineralocorticoid receptor antagonists (MRA) modulate cardiac fibrosis in HF patients, and have been shown to improve long term outcomes. We examined whether treatment effects from MRA use differed by Gal-3 levels in ambulatory heart failure patients enrolled in the HF-ACTION study. METHODS AND RESULTS: HF-ACTION was a randomized controlled trial of exercise training versus usual care in patients with HF due to LV systolic dysfunction (NYHA Class II–IV, LVEF ≤ 0.35, median follow-up 2.5 years). Galectin-3 was assessed at baseline in 895 patients. The endpoint was all-cause mortality or all-cause hospitalization (ACM+ACH); all-cause mortality (ACM) was a key secondary endpoint. A differential association of MRA use by increasing Gal3 concentration was tested using interaction terms in Cox proportional hazards models, adjusted for covariates previously identified in this cohort, as well as age, sex, and race. Inverse Propensity Weighted (IPW) methods were also used to assess this association. Approximately half the patients were on an MRA (n=401). There was no significant interaction for the associations of Gal-3 levels and MRA use on either endpoint (adjusted interaction p-value=0.76 for ACM+ACH; p=0.26 for ACM). There was no evidence of improved outcomes for patients on an MRA compared to those not on MRA on either endpoint (HR=1.02, 95% CI [0.85–1.23], p=0.8; HR=1.15, 95% CI [0.82–1.61], p=0.4, respectively). IPW analysis was consistent with the results of the adjusted analysis. CONCLUSION: Our study showed no evidence of interaction between Gal-3 and treatment effect of MRA. Whether biomarkers may be used to predict which patients may benefit from an mineralocorticoid receptor antagonist in HF requires further investigation