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Marked differences have been described between women and men in disease prevalence, clinical presentation, response to treatment and outcomes. However, such data are scarce in the acutely ill. An awareness of differences related to biological sex is essential for the success of clinical care and outcomes in patients presenting with acute dyspnea, the most frequent cause of emergency department (ED) admission.The aim of the present study was to assess the effect of biological sex on 1-year all-cause mortality in patients presenting with acute dyspnea to the ED.Consecutive adult patients presenting with acute dyspnea in two Lithuanian EDs were included. Clinical characteristics, laboratory data and medication use at discharge were collected. Follow-up at 1 year was performed via national data registries.The primary outcome of the study was 1-year all-cause mortality. Hazard ratios (HRs) for 1-year mortality according to biological sex were calculated using a Cox proportional hazards regression model, with and without adjustment for the following confounders: age, systolic blood pressure, creatinine, sodium and hemoglobin.A total of 1455 patients were included. Women represented 43% of the study population. Compared to men, women were older [median (interquartile range [IQR]) age 74 (65-80) vs. 68 (59-77) years, P0.0001]. The duration of clinical signs before admission was shorter for women [median (IQR) duration 4 (1-14) vs. 7(2-14) days, P = 0.006]. Unadjusted 1-year all-cause mortality was significantly lower in women (21 vs. 28%, P = 0.001). Adjusted HR of 1-year all-cause mortality was lower in women when compared to men [HR 0.68 (0.53-0.88), P = 0.0028]. Additional sensitivity analyses confirmed the survival benefit for women in subgroups including age greater and lower than 75 years, the presence of comorbidities and causes of dyspnea (cardiac or noncardiac).Women have better 1-year survival than men after the initial ED presentation for acute dyspnea. Understanding the biological sex-related differences should lead toward precision medicine, and improve clinical decision-making to promote gender equality in health.

Background Data characterizing risk factors and long-term outcome studies on human immunodeficiency virus (HIV)-associated pulmonary hypertension (PH) in Africa are lacking. Methods The Pan African Pulmonary Hypertension Cohort, a multinational registry of 254 consecutive patients diagnosed with PH (97% of African descent) from 9 centers in 4 African countries was implemented. We compared baseline characteristics and 3-year survival of an HIV-infected cohort newly diagnosed with PH (PH/HIV+) to an HIV-uninfected cohort with PH (PH/HIV−). Results One hundred thirty-four participants with PH completed follow up (47 PH/HIV+ and 87 PH/HIV−; age median, 36 versus 44 years; P = .0004). Cardiovascular risk factors and comorbidities were similar except for previous tuberculosis (62% versus 18%, P < .0001). Six-minute walk distance (6MWD) Conclusions The PH/HIV + patients were younger and commonly had previous tuberculosis compared to PH/HIV− patients. Despite a better 6MWD at presentation, they had more signs and symptoms of early onset heart failure and a worse survival rate. Early echocardiography assessment should be performed in HIV-infected patients with history of tuberculosis who present with signs and symptoms of heart failure or posttuberculosis lung disease.

Background: Anthracycline therapy-related cardiac dysfunction (ATRCD) is the most notorious adverse side-effect of chemotherapy. It has become a significant cardiovascular health concern for long-term cancer survivors. With the emerging concept of subclinical ATRCD and newer diagnostictools (Speckle Tracking Echocardiography (STE) and biomarkers), detecting anthracycline cardiac toxicity at an early stage has become an important step to prevent severe cardiac dysfunction and improve the cardiovascular outcome in cancer survivors. Despite the increasing population at risk in sub-Saharan Africa (SSA), there is no contemporary data in Uganda to address the burden, pathogenesis and risk factors of subclinical ATRCD. This big gap in knowledge has led to a lack of local guidelines for monitoring and management of ATRCD. Methods: SATRACD (Detecting Subclinical Anthracycline Therapy Related Cardiac Dysfunction In Low Income Country) study is an observational prospective cohort study. Three hundred and fifty-three anthracycline naïve cancer patients will be recruited at baseline. Patients are followed up on completion of anthracycline-based chemotherapy and at 6 months after completion of anthracycline therapy. Data on demographics, cancer profile and clinical presentation will be collected at baseline. Comprehensive cardiac assessment will be performed at each visit, including electrocardiogram, conventional echo- cardiography, STE, cardiac and oxidative stress markers. We will be able to determine the incidence of subclinical and clinical ATRCD at 6 months after completion of anthracycline therapy, determine whether hypertension is a major risk factor for ATRCD, evaluate the role of conventional echocardiography parameters, and biomarkers for detecting subclinical ATRCD. Conclusion: This SATRACD study will provide contemporary data on Ugandan cancer patients who have subclinical and clinical ATRCD, help in the development of local strategies to prevent and manage ATRCD, and improve cardiovascular outcome for Ugandan cancer survivors. Keywords: SATRACD study; subclinical anthracycline therapy; cardiac dysfunction; low income country.

Aims: To investigate the incidence of anthracycline therapy-related cardiac dysfunction (ATRCD) and its predictors among Ugandan cancer patients. Patients & methods: The study recruited 207 cancer patients who were followed for 6 months after ending anthracycline therapy. Global longitudinal strain and troponin-I were the diagnostic tools. Results & conclusions: The cumulative incidences of subclinical and clinical ATRCD were 35.0 and 8.8% respectively. The predictors of clinical ATRCD were HIV infection (hazard ratio [HR]: 3.04; 95% CI: 1.26–7.32; p = 0.013), lower baseline global longitudinal strain (HR: 0.61; 95% CI: 0.53–0.71; p

International audience; Aims Our objectives were to validate a murine model of chronic cardiotoxicity induced by Doxorubicin (Dox) and Trastuzumab (Trast) and to test the potential cardio-protective effect of metoprolol. Methods and results Male C57Bl6 mice were intraperitoneally injected during 2 weeks with Dox (24 mg/kg) or saline, and then with Trast (10 mg/kg) or saline for two more weeks. Half of the mice received metoprolol (100 mg/kg). Cardiotoxicity was defined by a decline in left ventricular ejection fraction (LVEF) ≥ 10 points. At Day 42, Dox + Trast-treated mice exhibited a 13-points decline in LVEF (74 ± 2.6% vs. 87 ± 0.8% for control mice, P < 0.001) and a severe cardiac atrophy (heart weight: 105 ± 2.7 mg vs. 119 ± 3.9 mg for control mice, P < 0.01). This cardiac atrophy resulted from an excess of cardiac necrosis (assessed by plasma cardiac troponin I level: 3.2 ± 0.4 ng/L vs. 1.3 ± 0.06 ng/L for control mice, P < 0.01), an increase in apoptosis (caspase 3 activity showing a six-fold increase for Dox + Trast-treated mice vs. controls, P < 0.001), and cardiomyocyte atrophy (myocyte size: 0.67 ± 0.08 μm 2 vs. 1.36 ± 0.10 μm 2 for control mice, P < 0.001). In addition, Dox + Trast-treated mice were shown to have an increased cardiac oxidative stress (164 ± 14 dihydroethidine-marked nuclei per area vs. 56 ± 9.5 for control mice, P < 0.01) and increased cardiac fibrosis (the semi-quantitative fibrosis score was threefold higher for Dox + Trast-treated mice as compared with controls, P < 0.01). Metoprolol was not able to prevent either the decrease in LVEF or the severe cardiac atrophy, the cardiac necrosis, and the cardiac remodelling induced by chemotherapies. Conclusion A murine model of chronic cardiotoxicity induced by Dox and Trast was characterized by a decrease in cardiac function, a cardiac apoptosis and necrosis leading to cardiomyocyte atrophy. Metoprolol did not prevent this cardiotoxicity.

Critical care 25(1), 61 (2021). doi:10.1186/s13054-021-03471-2, Published by BioMed Centra, London

Aims The relationship between N‐terminal pro‐brain natriuretic peptide (NT‐pro‐BNP) and galectin‐3 and outcomes has not been studied in African patients with acute heart failure (AHF). The current analysis sought to describe the association between plasma levels of NT‐pro‐BNP and galectin‐3 and cardiovascular (CV) death or heart failure (HF) hospitalization, as well as their associations with symptoms and echocardiography markers of left and right ventricular remodelling among AHF patientsv in sub‐Saharan Africa. Methods and results In a subset of 80 patients with complete data in a study assessing the effects of hydralazine and nitrates in patients with AHF (BAHEF trial; NCT01822808), NT‐pro‐BNP and galectin‐3 analyses were performed, and the association with various characteristics and outcome measures assessed. The mean age of the patients for whom the aforementioned biomarkers were measured was 52.6 years, with 52.5% women. Galectin‐3 at baseline predicted changes (Week 24 to baseline) in left ventricular ejection fraction, left ventricular end‐systolic diameter, left ventricular end‐diastolic diameter, and tricuspid annular plane systolic excursion. Biomarkers and their changes were not associated with changes in 6 min walk test at 24 weeks. Baseline galectin‐3 and change in NT‐pro‐BNP were associated with improvements in dyspnoea at 24 weeks. Nine patients had an HF readmission or died of CV causes through 24 weeks (11.6%). Both biomarkers at baseline predicted combined CV death or HF hospitalization through Week 24 (P‐values = 0.0328 and 0.0001, respectively). Conclusions In a cohort of patients with AHF from sub‐Saharan Africa, NT‐pro‐BNP and galectin‐3 at baseline and their changes were associated with some changes in dyspnoea, echocardiographic remodelling, and CV death or HF hospitalization through Week 24. These tests have potential of being used for risk stratification of AHF patients in sub‐Saharan Africa where resources are scarce.

Hormones have a vital duty in the conservation of physiological cardiovascular function during pregnancy. Alterations in oestrogen, progesterone and prolactin levels are associated with changes in the cardiovascular system to support the growing foetus and counteract pregnancy stresses. Pregnancy hormones are, however, also linked to numerous pathophysiological outcomes on the cardiovascular system. The expression and effects of the three main pregnancy hormones (oestrogen, prolactin and progesterone) vary depending on the gestation period. However, the reaction of a target cell also depends on the abundance of hormone receptors and impacts put forth by other hormones. Hormonal interaction may be synergistic, antagonistic or permissive. It is crucial to explore the cross talk of pregnancy hormones during gestation, as this may have a greater impact on the overall changes to the cardiovascular system.

Additional file 8: Table.

Peripartum cardiomyopathy (PPCM) is a life-threatening cardiomyopathy characterized by left ventricular (LV) systolic dysfunction late in pregnancy, during delivery, or in the first postpartum months, in women with no previously known heart disease. Today it is assumed that multiple pathomechanisms may induce the disease, including genetic and environmental factors. There is evidence that these factors may merge on common pathomechanistic pathways such as unbalanced oxidative stress and the cleavage of the nursing hormone prolactin (PRL) into an angiostatic 16 kDa-PRL fragment with subsequent vascular impairment and heart failure. Recent research on specific and common pathomechanisms discovered disease-specific biomarkers and therapies. The current knowledge on etiology and pathomechanisms of PPCM is summarized in the present chapter.

Background The link between cancer and cardiovascular disease is firmly established. We sought to investigate the prevalence of cardiovascular disease (CVD) risk factors in Uganda cancer patients, their pre-chemotherapy left ventricular strain echocardiographic pattern and its associations with the CVD risk factors. Methods and results Baseline pre-chemotherapy data of patients who were enrolled in the SATRACD study (a cancer cohort, who were planned for anthracycline therapy), were analyzed. The prevalence of cardiovascular risk factors and baseline strain echocardiographic images were assessed. Among the 355 patients who were recruited over a period of 15 months, 283 (79.7%) were female, with a mean age of 43 years. The types of cancer of the study patients included breast cancer (70.6%), lymphomas, sarcomas, leukemias and hepatocellular carcinoma. Hypertension was the most common comorbidity (27.0%). The prevalence of obesity was 12.1% and that of HIV was 18.3%. All patients had a normal left ventricular ejection fraction (LVEF). The mean global longitudinal strain (GLS) was -20.92 ±2.43%, with females having a significantly higher GLS than males (-21.09±2.42 vs -20.25±2.39, p = 0.008). Fifty-three patients (14.9%) had suboptimal GLS (absolute GLS≤18.00%), which was associated with obesity (POR = 3.07; 95% CI, 1.31–6.98; p = 0.003), alcohol use (POR = 1.94; 95% CI, 1.01–3.74; p = 0.044), long QTc interval in electrocardiogram (POR = 2.54; 95% CI, 1.06–5.74; p = 0.015,) and impaired left ventricular relaxation (POR = 2.24; 95% CI, 1.17–4.25; p = 0.007). On multivariable logistic regression analysis, obesity (POR = 2.95; 95% CI, 1.24–7.03; p = 0.014) was the only independent factor associated with suboptimal GLS. Conclusion There is high prevalence and a unique pattern of cardiovascular risk factors in Uganda cancer patients. In cancer patients with cardiovascular risk conditions, there is reduction in GLS despite preserved LVEF. Longitudinal research is needed to study the predictive value of cardiovascular risk factors and baseline GLS for post chemotherapy cardiac dysfunction.

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 >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 >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 >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.

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.

Sepsis is a global economic and health burden. Dipeptidyl peptidase 3 (DPP3) is elevated in the plasma of septic patients. The highest levels of circulating DPP3 (cDPP3) are found in non-survivor septic shock patients. The aim of this study was to evaluate the benefits of inhibiting cDPP3 by a specific antibody, Procizumab (PCZ), on cardiac function in an experimental model of sepsis, the caecal ligature and puncture (CLP) model. Rats were monitored by invasive blood pressure and echocardiography. Results are presented as mean ± SD, with p

Importance Arrhythmias are an important cause of maternal morbidity and mortality but remain difficult to diagnose. Objective To compare implantable loop recorder (ILR) plus 24-hour Holter electrocardiographic (ECG) monitoring with standard 24-hour Holter ECG monitoring alone in terms of acceptability, ability to identify significant arrythmias, and effect on management and pregnancy outcome in women who were symptomatic or at high risk of arrythmia because of underlying structural heart disease. Design, Setting, and Participants This single-center, prospective randomized clinical trial recruited 40 consecutive patients from the Cardiac Disease and Maternity Clinic at Groote Schuur Hospital in Cape Town, South Africa. Pregnant patients with symptoms of arrhythmia and/or structural heart disease at risk of arrhythmia were included. Intervention Patients were randomized to standard care (SC; 24-hour Holter ECG monitoring [n = 20]) or standard care plus ILR (SC-ILR; 24-hour Holter ECG monitoring plus ILR [n = 20]). Only 17 consented to ILR insertion, and the 3 who declined ILR were allocated to the SC group. Main Outcomes and Measures Arrhythmias considered included atrial fibrillation, atrial flutter, premature ventricular complexes, supraventricular tachycardia, ventricular tachycardia, or ventricular fibrillation. Results Among the 40 women in this trial, the mean (SD) age was 28.4 (5.5) years. Holter monitoring detected arrhythmias in 3 of 23 patients (13%) in the SC group and 4 of 17 patients (24%) in the SC-ILR group compared with 9 of 17 patients (53%) patients who had arrhythmias detected by ILR. Seven patients (4 with supraventricular tachycardia, 1 with premature ventricular complexes, and 2 with paroxysmal atrial fibrillation recorded by ILR) did not have arrhythmias detected by 24-hour Holter monitoring. Three of these 7 patients (43%) had a change in management as a result of their ILR recordings. There were no maternal deaths. However, the SC group had a significantly lower mean (SD) gestational stage at delivery (35 [5] weeks vs 38 [2], P = .04). Conclusions and Relevance The ILR was better than 24-hour Holter monitoring in detecting arrhythmias, which led to a change in management for a significant proportion of patients. Our findings suggest that ILR may be beneficial for pregnant women at risk of arrhythmia. Trial Registration ClinicalTrials.gov Identifier: NCT02249195

Additional file 2: Table S1. Probabilistic antimicrobial therapy used in rat CLP models in the literature published in 2018 and 2019

Additional file 1: Figure S1. Peritoneal fluid culture analysis of 16 rats 16 hours after CLP

Gene therapy is a promising strategy to cure rare diseases. The lack of regulatory sequences ensuring specific and robust expression in skeletal and cardiac muscle is a substantial limitation of gene therapy efficiency targeting the muscle tissue. Here we describe a novel muscle hybrid (MH) promoter that is highly active in both skeletal and cardiac muscle cells. It has an easily exchangeable modular structure, including an intronic module that highly enhances the expression of the gene driven by it. In cultured myoblasts, myotubes, and cardiomyocytes, the MH promoter gives relatively stable expression as well as higher activity and protein levels than the standard CMV and desmin gene promoters or the previously developed synthetic or CKM-based promoters. Combined with AAV2/9, the MH promoter also provides a high in vivo expression level in skeletal muscle and the heart after both intramuscular and systemic delivery. It is much more efficient than the desmin-encoding gene promoter, and it maintains the same specificity. This novel promoter has potential for gene therapy in muscle cells. It can provide stable transgene expression, ensuring high levels of therapeutic protein, and limited side effects because of its specificity. This constitutes an improvement in the efficiency of genetic disease therapy. Keywords: muscle promoter, expression cassette, AAV, vector, skeletal muscles, heart, C2C12, myotubes

International audience; We assessed the potential of Lmna-mRNA repair by spliceosome-mediated RNA trans-splicing as a therapeutic approach for LMNA-related congenital muscular dystrophy. This gene therapy strategy leads to reduction of mutated transcript expression for the benefit of corresponding wild-type (WT) transcripts. We developed 5 0-RNA pretrans-splicing molecules containing the first five exons of Lmna and targeting intron 5 of Lmna pre-mRNA. Among nine pre-trans-splicing molecules, differing in the targeted sequence in intron 5 and tested in C2C12 myoblasts, three induced trans-splicing events on endogenous Lmna mRNA and confirmed at protein level. Further analyses performed in primary myotubes derived from an LMNA-related congenital muscular dystrophy (L-CMD) mouse model led to a partial rescue of the mutant phenotype. Finally, we tested this approach in vivo using adeno-associated virus (AAV) delivery in newborn mice and showed that trans-splicing events occurred in WT mice 50 days after AAV delivery, although at a low rate. Altogether, while these results provide the first evidence for reprogramming LMNA mRNA in vitro, strategies to improve the rate of trans-splicing events still need to be developed for efficient application of this therapeutic approach in vivo.

Background Cardiac arrhythmia is an important cause of maternal morbidity and mortality in pregnancy, but is difficult to diagnose. Purpose The aim of this single-centre, prospective, randomized pilot study was to compare the implantable loop recorder (ILR) with standard assessment of arrhythmia (12-lead ECG; 24-hour Holter ECG) in terms of acceptability, detection of arrhythmias and impact on outcome in pregnant women with symptomatic arrhythmias and/or structural heart disease (SHD). Methods The study recruited 40 consecutive patients from a weekly, dedicated cardiac obstetric clinic. Inclusion criteria: symptoms of arrhythmia and/or having SHD at risk of arrhythmia. Patients were randomized to either standard care (SC) or standard care plus ILR (SC-ILR). ILR recordings were read at the monthly visits and/or when presenting with symptoms. Results There were no demographic differences between the study groups. Seventeen patients consented to ILR insertion, all of whom found the procedure acceptable. No arrhythmias were recorded by the 12-lead ECGs. Holter monitoring detected arrhythmias in 10 of 23 patients (43%) from the SC group. In the SC-ILR group, 8 of 17 patients (47%) had arrhythmias detected by Holter, whereas 13 of 17 patients (76%) patients had arrhythmias detected by ILR (p=0.157). One of 4 patients with supraventricular tachycardia, 2 of 3 patients with premature ventricular complexes and 2 patients with paroxysmal atrial fibrillation (AF) recorded by ILR did not have the arrhythmias detected by Holter monitoring (Figure 1A shows a scatter plot of the variable R-R intervals seen in AF and 1B a rhythm strip of AF with irregular RR intervals and the absence of P waves, both downloaded from the ILR). Four of these 5 patients (80%) had a change in management as a direct result of their ILR recordings. There were no maternal deaths up to 42 days postpartum in either of the study groups. Nine babies were born with a low birthweight ( Figure 1 Conclusion(s) This study suggests that an ILR is an acceptable diagnostic modality in pregnant women with a suspected or at risk of arrhythmia. The ILR increased the diagnostic yield to detect arrhythmias that were not detected by routine ECG and Holter monitoring which led to a change in management in the SC-ILR group and was associated with better maternal and neonatal outcomes. The impact of ILR monitoring should be further assessed in larger studies with longer follow up.

Aims Acute heart failure is a high mortality disease and its pathophysiology is not completely understood. Dipeptidyl peptidase 3 (DPP3) is a cytosolic enzyme involved in angiotensin II and enkephalins cleavage. The aim of this study was to investigate the association of circulating DPP3 (cDPP3) levels and mortality in cardiogenic shock patients and to determine the effects of high cDPP3 on organ function in a heart failure (HF) model in mice. Methods and results cDPP3 was measured in 174 patients in cardiogenic shock and high cDPP3 levels were associated with an increased short-term mortality risk (standardized hazard ratio: 1.4 (1.1-1.8)) and severe organ dysfunction. Additionally, a rapid decrease in cDPP3 in cardiogenic shock patients within 24 h of admission was associated with a favourable outcome. This study showed that injection of DPP3 induced myocardial depression (-10 ± 2% of shortening fraction) and impaired kidney haemodynamics (+0.30 ± 0.02 of renal resistive index) in healthy mice. cDPP3 inhibition by Procizumab, a specific antibody directed against cDPP3, promptly normalized cardiac function and kidney haemodynamics in an acute heart failure mouse model, with a marked reduction in oxidative stress and inflammatory signalling. Conclusion Our study demonstrated cDPP3 is a newly discovered myocardial depressant factor, the levels of which at admission are associated with mortality in severe HF patients. Furthermore, inhibition of cDPP3 by Procizumab improved haemodynamics in a mouse model of HF. Our results suggest that DPP3 could be a new biomarker and biotarget for severe HF.

OBJECTIVE: To examine whether treatment with beta-blockers (BBs) in pregnant women with structural heart disease (SHD) resulted in a decrease in foetal birth weight (FBW) in a South African cohort. METHODS: This was a prospective cohort study conducted in a tertiary-level hospital in Cape Town from 2010 to 2016. Of the 178 pregnant women with SHD, 24.2% received BBs for a minimum of two weeks. Adverse foetal outcomes and mean FBW were compared between the BB groups and subgroups (congenital, valvular, cardiomyopathy and other). Adverse foetal outcome was defined as: low birth weight (LBW) < 2 500 g, Apgar score < 7, premature birth (< 37 weeks) and small for gestational age (SGA). RESULTS: BB exposure during pregnancy was found to be associated with a non-significant increased FBW (2 912 vs 2 807 g, p = 0.347). A significant decrease (p = 0.009) was noted in FBW for valvular SHD pregnancies using BBs, while a significant increase (p = 0.049) was observed for the same outcome in the cardiomyopathy subgroup using BBs. A significant increase was observed for SGA (p = 0.010) and LBW (p = 0.003) pregnancies within the valvular subgroup when exposed to BBs. CONCLUSION: BB use in pregnant women with SHD in a South African cohort showed no association with a decrease in FBW or an increase in adverse foetal outcomes when compared to non-BB usage.