A systematic review and meta-analysis of the diagnosis and surgical management of carcinoid heart disease

IntroductionCarcinoid heart disease (CHD), a complication of carcinoid syndrome (CS), is a rare condition that can lead to right sided valvular heart disease and has been traditionally associated with a poor prognosis. We conducted a systematic review and meta-analysis to explore the accuracy of biomarkers and echocardiography in diagnosing CHD amongst patients who are already known to have neuroendocrine tumours and to assess whether surgical management of CHD leads to a reduction in mortality.MethodsA systematic literature search of MEDLINE, EMBASE, EBM Reviews, Google Scholar, ClinicalTrials.gov was conducted. All studies on patients with carcinoid heart disease (CHD) reporting on biomarkers, echocardiographic and surgical outcomes were included. The National Heart, Lung, and Blood Institute quality assessment tool was used to assess the methodological study quality. Data analysis was performed using Stata Statistical Software and R Studio, and individual meta-analyses were performed for biomarkers, echocardiographic findings, and surgical outcomes.ResultsA total of 36 articles were included in the systematic review analysis. N terminal pro-brain natriuretic peptide (NTproBNP) and 5-hydroxyindole acetate (5-HIAA) levels were higher in patients with CHD compared with those without CHD. 32% of CS patients had echocardiographic evidence of cardiac involvement, of which 79% involved tricuspid valve abnormalities. Moderate-severe tricuspid regurgitation was the most common echocardiographic abnormality (70% of patients). However, these analyses had substantial heterogeneity due to the high variability of cardiac involvement across studies. Pooled surgical mortality for CHD was 11% at 1 month, 31% at 12 months and 56% at 24 months. When assessing surgical outcomes longitudinally, the one-month surgical results showed a trend towards more recent surgeries having lower mortality rates than those reported in earlier years, however this was not statistically significant.DiscussionThere is not enough data in current literature to determine a clear cut-off value of NTproBNP and 5-HIAA to help diagnose or determine CHD severity. Surgical management of CHD is yet to show significant mortality benefit, and there are no consistent comparisons to medical treatment in current literature

Endothelial dysfunction and glycocalyx shedding in heart failure:insights from patients receiving cardiac resynchronisation therapy

To determine (a) whether chronic heart failure with reduced ejection fraction (HFrEF) is associated with increased glycocalyx shedding; (b) whether glycocalyx shedding in HFrEF with left ventricular dyssynchrony is related to inflammation, endothelial dysfunction and/or redox stress and is ameliorated by cardiac resynchronisation therapy. Glycocalyx shedding has been reported to be increased in heart failure and is a marker of increased mortality. Its role in dyssynchronous systolic heart failure and the effects of cardiac resynchronisation therapy (CRT) are largely unknown. Twenty-six patients with dyssynchronous HFrEF were evaluated before and 6 months after CRT insertion. Echocardiographic septal to posterior wall delay (SPWD) assessed intra-ventricular mechanical dyssynchrony, and quality of life, integrity of nitric oxide (NO) signalling, inflammatory and redox-related biomarkers were measured. Glycocalyx shedding was quantitated via plasma levels of the glycocalyx component, syndecan-1. Syndecan-1 levels pre-CRT were inversely correlated with LVEF (r = - 0.45, p = 0.02) and directly with SPWD (r = 0.44, p = 0.02), QOL (r = 0.39, p = 0.04), plasma NT-proBNP (r = 0.43, p = 0.02), and the inflammatory marker, symmetric dimethylarginine (SDMA) (r = 0.54, p = 0.003). On multivariate analysis, syndecan-1 levels were predicted by SPWD and SDMA (β = 0.42, p = 0.009 and β = 0.54, p = 0.001, respectively). No significant correlation was found between syndecan-1 levels and other markers of endothelial dysfunction/inflammatory activation. Following CRT there was no significant change in syndecan-1 levels. In patients with dyssynchronous HFrEF, markers of glycocalyx shedding are associated with the magnitude of mechanical dyssynchrony and elevation of SDMA levels and inversely with LVEF. However, CRT does not reverse this process

Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial

Background: Semaglutide, a GLP-1 receptor agonist, reduces the risk of major adverse cardiovascular events (MACE) in people with overweight or obesity, but the effects of this drug on outcomes in patients with atherosclerotic cardiovascular disease and heart failure are unknown. We report a prespecified analysis of the effect of once-weekly subcutaneous semaglutide 2·4 mg on ischaemic and heart failure cardiovascular outcomes. We aimed to investigate if semaglutide was beneficial in patients with atherosclerotic cardiovascular disease with a history of heart failure compared with placebo; if there was a difference in outcome in patients designated as having heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction; and if the efficacy and safety of semaglutide in patients with heart failure was related to baseline characteristics or subtype of heart failure. Methods: The SELECT trial was a randomised, double-blind, multicentre, placebo-controlled, event-driven phase 3 trial in 41 countries. Adults aged 45 years and older, with a BMI of 27 kg/m2 or greater and established cardiovascular disease were eligible for the study. Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo. In a prespecified analysis, we examined the effect of semaglutide compared with placebo in patients with and without a history of heart failure at enrolment, subclassified as heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, or unclassified heart failure. Endpoints comprised MACE (a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death); a composite heart failure outcome (cardiovascular death or hospitalisation or urgent hospital visit for heart failure); cardiovascular death; and all-cause death. The study is registered with ClinicalTrials.gov, NCT03574597. Findings: Between Oct 31, 2018, and March 31, 2021, 17 604 patients with a mean age of 61·6 years (SD 8·9) and a mean BMI of 33·4 kg/m2 (5·0) were randomly assigned to receive semaglutide (8803 [50·0%] patients) or placebo (8801 [50·0%] patients). 4286 (24·3%) of 17 604 patients had a history of investigator-defined heart failure at enrolment: 2273 (53·0%) of 4286 patients had heart failure with preserved ejection fraction, 1347 (31·4%) had heart failure with reduced ejection fraction, and 666 (15·5%) had unclassified heart failure. Baseline characteristics were similar between patients with and without heart failure. Patients with heart failure had a higher incidence of clinical events. Semaglutide improved all outcome measures in patients with heart failure at random assignment compared with those without heart failure (hazard ratio [HR] 0·72, 95% CI 0·60-0·87 for MACE; 0·79, 0·64-0·98 for the heart failure composite endpoint; 0·76, 0·59-0·97 for cardiovascular death; and 0·81, 0·66-1·00 for all-cause death; all pinteraction>0·19). Treatment with semaglutide resulted in improved outcomes in both the heart failure with reduced ejection fraction (HR 0·65, 95% CI 0·49-0·87 for MACE; 0·79, 0·58-1·08 for the composite heart failure endpoint) and heart failure with preserved ejection fraction groups (0·69, 0·51-0·91 for MACE; 0·75, 0·52-1·07 for the composite heart failure endpoint), although patients with heart failure with reduced ejection fraction had higher absolute event rates than those with heart failure with preserved ejection fraction. For MACE and the heart failure composite, there were no significant differences in benefits across baseline age, sex, BMI, New York Heart Association status, and diuretic use. Serious adverse events were less frequent with semaglutide versus placebo, regardless of heart failure subtype. Interpretation: In patients with atherosclerotic cardiovascular diease and overweight or obesity, treatment with semaglutide 2·4 mg reduced MACE and composite heart failure endpoints compared with placebo in those with and without clinical heart failure, regardless of heart failure subtype. Our findings could facilitate prescribing and result in improved clinical outcomes for this patient group. Funding: Novo Nordisk

Agreement of aneroid and oscillometric blood pressure devices used in pregnancy

Objectives: The objective of this study was to compare three automated blood pressure devices (Microlife VSA, Uscom BP + and Tensiomed Arteriograph) with an aneroid device in an Australian antenatal population to determine an accurate and reliable alternative method of measuring blood pressure in pregnant women. Study design: This observational, prospective study recruited a random sample of 200 pregnant women of any gestation attending an antenatal clinic in an Australian hospital. Each participant had two peripheral blood pressure measurements per instrument performed, resulting in eight measurements per participant. Main outcome measurements: Infra- and inter-device reliability of peripheral blood pressure measurements made by the aneroid device and the three automated brachial-cuff oscillometric devices were assessed. The agreement between devices was graded according to standardised criteria. Results: Both intra- and inter-device reliability of blood pressure measurements of the four devices in this study were found to be 'excellent' (ICCs > 0.75). Microlife VSA and Uscom BP + showed acceptable levels of agreement (+/- 5mmHg) when compared to the aneroid device. Arteriograph did not show an acceptable level of agreement with the aneroid device for systolic blood pressure, but did for diastolic blood pressure. Conclusion: Accurate automated devices may ensure consistent assessment of blood pressure in the antenatal setting. Our results suggest that Microlife VSA and Uscom BP + may be suitable alternatives to the aneroid device for use in the antenatal setting. Further studies assessing both auscultatory and oscillometric blood pressure devices in pregnancy, and especially in hypertensive cohorts, are required

Influence of Socioeconomic Status on the Association Between Pregnancy Complications and Premature Coronary Artery Disease: Linking Three Cohorts

Background: We hypothesized that there is an influence of socioeconomic status (SES) on association between pregnancy complications and premature coronary artery disease (PCAD) risk. Materials and Methods: This project involved a data linkage approach merging three databases of South Australian cohorts using retrospective, age-matched case?control study design. Cases (n?=?721), that is, women aged <60 years from Coronary Angiogram Database of South Australia (CADOSA) were linked to South Australian Perinatal Statistics Collection (SAPSC) to ascertain prior pregnancy outcomes and SES. Controls (n?=?194) were selected from North West Adelaide Health Study (NWAHS), comprising women who were healthy or had health conditions unrelated to CAD, age matched to CADOSA (?5 years), and linked to SAPSC to determine prior pregnancy outcomes and SES. This project performed comparative analysis of SES using socioeconomic indexes for areas?index of relative socioeconomic advantage and disadvantage (SEIFA-IRSAD) scores across three databases. Results: Findings revealed that SEIFA-IRSAD scores at the time of pregnancy (p-value?=?0.005) and increase in SEIFA-IRSAD scores over time (p-value?=?0.040) were significantly associated with PCAD. In addition, when models were adjusted for SEIFA-IRSAD scores at the time of pregnancy and age, risk factors including placenta-mediated pregnancy complications such as preterm birth (odds ratio [OR]?=?4.77, 95% confidence interval [CI]: 1.74?13.03) and history of a miscarriage (OR?=?2.14, 95% CI: 1.02?4.49), and cardiovascular disease (CVD) risk factors including smoking (OR?=?8.60, 95% CI: 3.25?22.75) were significantly associated with PCAD. When the model was adjusted for change in SEIFA-IRSAD scores (from CADOSA/NWAHS to SAPSC) and age, pregnancy-mediated pregnancy complications including preterm birth (OR?=?4.40, 95% CI: 1.61?12.05) and history of a miscarriage (OR?=?2.09, 95% CI: 1.00?4.35), and CVD risk factor smoking (OR?=?8.75, 95% CI: 3.32?23.07) were significantly associated with PCAD. Conclusion: SES at the time of pregnancy and change in SES were not associated with PCAD risk

The association of breast feeding for at least six months with hemodynamic and metabolic health of women and their children aged three years: an observational cohort study

Abstract Background Breastfeeding is important for both mother and child in reducing risk of future cardiovascular disease. Therefore, it may be an effective method to improve cardio-metabolic health, particularly those who are exposed to pregnancy complications which increase later CVD risk for both mother and child. The aim of this study is to assess differences in cardiometabolic health at three years postpartum in mothers who breastfed for at least six months and their children compared to those who did not. Methods Women and children from the Screening Tests to Predict Poor Outcomes of Pregnancy (STOP) study (2015–2017) were invited to attend a health check-up at three years postpartum. Women’s breastfeeding status at least six months postpartum was ascertained through their child health record. Anthropometric and hemodynamic measurements were taken from women and their children. A fasting blood sample was taken from women to measure blood glucose and lipids. Results A total of 160 woman-child dyads were assessed in this study. Women who breastfed for at least six months had significantly lower maternal BMI, systolic blood pressure, diastolic blood pressure, mean arterial pressure, central systolic blood pressure, and central diastolic blood pressure than those who did not and this did not change after adjusting for BMI and socioeconomic index in early pregnancy, prenatal smoking and maternal age in early pregnancy. Subgroup analysis on women who had one or more pregnancy complications during the index pregnancy (i.e. preeclampsia, gestational hypertension, delivery of a small for gestational age infant, delivery of a preterm infant, and/or gestational diabetes mellitus) demonstrated that women who breastfed for at least six months had significantly lower maternal systolic and diastolic blood pressures, serum insulin and triglycerides, and higher HDL cholesterol. There were no differences in child anthropometric or hemodynamic variables at three years of age between those children who had been breastfed for at least six months and those who had not. Conclusion Breastfeeding for at least six months may reduce some maternal; cardiovascular risk factors in women at three years postpartum, in particular, in those who have experienced a complication of pregnancy. Trial registration ACTRN12614000985684 (12/09/2014)