Prevalence of pre-eclampsia and adverse pregnancy outcomes in women with pre-existing cardiomyopathy: a multi-centre retrospective cohort study.

Pre-eclampsia is associated with postnatal cardiac dysfunction; however, the nature of this relationship remains uncertain. This multicentre retrospective cohort study aimed to determine the prevalence of pre-eclampsia in women with pre-existing cardiac dysfunction (left ventricular ejection fraction < 55%) and explore the relationship between pregnancy outcome and pre-pregnancy cardiac phenotype. In this cohort of 282 pregnancies, pre-eclampsia prevalence was not significantly increased (4.6% [95% C.I 2.2-7.0%] vs. population prevalence of 4.6% [95% C.I. 2.7-8.2], p = 0.99); 12/13 women had concurrent obstetric/medical risk factors for pre-eclampsia. The prevalence of preterm pre-eclampsia (< 37 weeks) and fetal growth restriction (FGR) was increased (1.8% vs. 0.7%, p = 0.03; 15.2% vs. 5.5%, p < 0.001, respectively). Neither systolic nor diastolic function correlated with pregnancy outcome. Antenatal ß blockers (n = 116) were associated with lower birthweight Z score (adjusted difference - 0.31 [95% C.I. - 0.61 to - 0.01], p = 0.04). To conclude, this study demonstrated a modest increase in preterm pre-eclampsia and significant increase in FGR in women with pre-existing cardiac dysfunction. Our results do not necessarily support a causal relationship between cardiac dysfunction and pre-eclampsia, especially given the population's background risk status. The mechanism underpinning the relationship between cardiac dysfunction and FGR merits further research but could be influenced by concomitant ß blocker use.

Perturbations in cardiac metabolism in a human model of acute myocardial ischaemia.

INTRODUCTION: Acute myocardial ischaemia and the transition from reversible to irreversible myocardial injury are associated with abnormal metabolic patterns. Advances in metabolomics have extended our capabilities to define these metabolic perturbations on a metabolome-wide scale. OBJECTIVES: This study was designed to identify cardiac metabolic changes in serum during the first 5 min following early myocardial ischaemia in humans, applying an untargeted metabolomics approach. METHODS: Peripheral venous samples were collected from 46 patients in a discovery study (DS) and a validation study (VS) (25 for DS, 21 for VS). Coronary sinus venous samples were collected from 7 patients (4 for DS, 3 for VS). Acute myocardial ischaemia was induced by transient coronary occlusion during percutaneous coronary intervention (PCI). Plasma samples were collected at baseline (prior to PCI) and at 1 and 5 min post-coronary occlusion. Samples were analyzed by Ultra Performance Liquid Chromatography-Mass Spectrometry in an untargeted metabolomics approach. RESULTS: The study observed changes in the circulating levels of metabolites at 1 and 5 min following transient coronary ischaemia. Both DS and VS identified 54 and 55 metabolites as significant (P < 0.05) when compared to baseline levels, respectively. Fatty acid beta-oxidation and anaerobic respiration, lysoglycerophospholipids, arachidonic acid, docosahexaenoic acid, tryptophan metabolism and sphingosine-1-phosphate were identified as mechanistically important. CONCLUSION: Using an untargeted metabolomics approach, the study identified important cardiac metabolic changes in peripheral and coronary sinus plasma, in a human model of controlled acute myocardial ischaemia. Distinct classes of metabolites were shown to be involved in the rapid cardiac response to ischemia and provide insights into diagnostic and interventional targets.

Homozygous familial hypercholesterolemia with an update on cholesterol management.

Familial hypercholesterolemia (FH) is an autosomal dominant condition that increases the risk of premature cardiovascular disease. Despite advances in treatment, it remains under detected and under treated. As an inherited condition, it poses a risk to the patient and family members. Most cases are due to defective low-density lipoprotein receptor (LDLR) activity. Heterozygous mutations are common (1:250-1:300). Homozygous FH is very rare (2-3 in a million), with higher circulating cholesterol levels and a poorer cardiovascular prognosis. We present the management of a case of homozygous hypercholesterolemia due to homozygous LDLR mutation. The patient subsequently developed severe coronary artery and aortic valve disease despite aggressive lipid-lowering therapy. We review advanced lipid management options that include lipoprotein apheresis, Proprotein Convertase Subtilisin/Kexin type 9 inhibition, and the microsomal triglyceride transfer protein inhibitor lomitapide.

Cardiopulmonary exercise testing in the evaluation of liver disease in adults who have had the Fontan operation.

BACKGROUND: Liver disease (LD) is a long-term complication in patients with a single ventricle who have had the Fontan operation. A decline in cardiopulmonary exercise testing (CPET) variables is associated with increased risk of hospitalization, but its association with LD is unknown. AIM: To determine the association between CPET variables and LD in adults who have had the Fontan operation. METHODS: We retrospectively reviewed the medical records from two tertiary institutions. RESULTS: We identified 114 adults (≥18 years; mean 30.9±7.4 years) who had undergone the Fontan operation: 56% were women; 63% had total cavopulmonary connection; 66% had New York Heart Association (NYHA) class I status; 42% had arrhythmias; 22% had systemic right ventricle; and 35% had ventricular dysfunction. Of 81 patients with liver-imaging data, 41% had LD (i.e. imaging evidence of cirrhosis, with or without portal hypertension, splenomegaly or varices). There were no differences in clinical or echocardiographic variables between those with and without LD. Among the 58 patients with CPET data, mean peak oxygen consumption (VO2) was 18.6±5.7mL/kg/min, per-cent-predicted peak VO2 was 53.9±15.5%, peak oxygen pulse was 9.3±2.9mL/beat and per-cent-predicted peak oxygen pulse was 82.6±21.5%. Of the 44 patients with liver and CPET data, each standard deviation decrease in per-cent-predicted peak VO2 (16%) and per-cent-predicted peak oxygen pulse (22%) was associated with a 2.3-fold increase in the odds of LD, after adjusting for NYHA, institution and Fontan type (P=0.04). Similarly, each standard deviation decrease in per-cent-predicted peak VO2 and oxygen pulse was associated with an estimated 5.9-year and 4.9-year earlier onset of LD, respectively (P>0.05). CONCLUSIONS: Decline in per-cent-predicted peak VO2 and oxygen pulse was associated with increased odds of LD in adults who had undergone the Fontan operation. Our study supports more rapid hepatic evaluation among patients with abnormal or worsening CPET variables.

Maternal heart rate during the first 48h postpartum: a retrospective cross sectional study.

OBJECTIVES: 1) Describe the distribution of heart rate in the first 48h postpartum in women with no evidence of sepsis, anaemia or haemorrhage. 2) Investigate the relationship between postpartum heart rate and other maternal factors. STUDY DESIGN: A retrospective cross-sectional study of postpartum women who delivered between July 2012 and June 2015 in a tertiary hospital. Data was analysed from the local maternity system and electronic vital signs database. The main outcome measures: Heart rate at 6, 12, 24 and 48h postpartum. RESULTS: Data were obtained on 11401 women. After exclusion of women with possible sepsis, anaemia or haemorrhage, 7627 heart rate readings from 5164 women were analysed. Mean heart rate (+2SD/+3SD) at 6h was 83.6 (108.2/120.6), 12h 84.5 (109.4/121.9), 24h 85.4 (110.4/122.9), and 48h 84.3 (109.7/122.4). There was statistical correlation of post partum heart rate with body mass index (BMI), age and discharge haemoglobin. CONCLUSION: This study describes the distribution of maternal heart rate in the early postpartum period, in women with no evidence of sepsis, anaemia or major haemorrhage. This will facilitate identification and appropriate investigation of women with abnormal heart rates. Although correlation with BMI, age and discharge haemoglobin was demonstrated, the differences were small and not clinically meaningful. Further work investigating the relationship between postpartum heart rate and poor maternal outcomes is required.

Forward and back aspiration during ST-elevation myocardial infarction: a feasibility study.

AIMS: The inability to optimise stent expansion fully whilst simultaneously preventing distal embolisation during ST-elevation myocardial infarction (STEMI) remains a clinical conundrum. We aimed to describe a newly devised angiographic strategy of "forward" and "back" aspiration that leads to more complete thrombus removal and prevention of distal embolisation, to allow high-pressure post-dilatation of the implanted stent to be performed. METHODS AND RESULTS: Forward aspiration was conducted with a conventional aspiration thrombectomy catheter, with bail-out aspiration thrombectomy for angiographically persistent thrombus utilising the larger bore 6 Fr (0.056") guide catheter extension system (GuideLiner; Vascular Solutions, Inc., Minneapolis, MN, USA). Back aspiration was undertaken with a deeply intubated GuideLiner or guide catheter with a vacuum induced within, extending to the inflated angioplasty balloon, to allow for proximal embolic protection during balloon deflation during all stages of the PCI procedure, including high-pressure post-dilatation of the stent to the visually estimated reference vessel diameter (RVD). Over a six-month period 30 consecutive cases were undertaken during working hours. Bail-out GuideLiner-assisted aspiration thrombectomy was performed in 9/30 cases because of inadequate thrombus removal with a conventional aspiration thrombectomy catheter. Back aspiration was performed in all cases. In 27/30 cases high-pressure post-dilatation of the stent was performed. The mean maximum post-dilatation balloon size and mean proximal reference vessel diameter did not significantly differ (3.60±0.41 mm vs. 3.65±0.45 mm, p=0.68). In all cases, implantation +/- post-dilatation of the stent to the visually estimated RVD was achievable without any deterioration in TIMI blood flow or myocardial blush grade. CONCLUSIONS: The strategy of forward and back aspiration to facilitate stent implantation and high-pressure post-dilatation during STEMI appears to be safe and effective. Randomised controlled trials are required to confirm the safety and efficacy of this newly devised angiographic strategy.

Benefit of endovascular stenting for aortic coarctation on systemic hypertension in adults.

BACKGROUND: Endovascular stenting is a recognised treatment strategy for aortic coarctation (CoA) in adults. We assessed systemic hypertension control and the need for antihypertensive therapy after CoA stenting in adults. METHODS: Data were collected prospectively on 54 patients (36 men; mean age: 34 ± 16 years) who underwent endovascular stenting for CoA over a 7-year period. Five patients were excluded as they did not attend follow-up appointments. Patients underwent clinical examination, including right arm systolic blood pressure (SBP) and 24-hour ambulatory blood pressure monitoring at baseline, 6-12 weeks and 9-12 months. RESULTS: There was a significant fall in mean peak-to-peak systolic gradient (PG) across the CoA after stenting (26 ± 11 mmHg vs. 5 ± 4 mmHg; P<0.01). There were successive reductions in right arm SBP and ambulatory SBP at baseline, 6-12 weeks and 9-12 months post-procedure (right arm: 155 ± 18 mmHg vs. 137 ± 17 mmHg vs. 142 ± 16 mmHg, respectively; all P-values <0.01; ambulatory: 142 ± 14 mmHg vs. 132 ± 16 mmHg vs. 131 ± 15 mmHg, respectively; all P-values <0.01). Twenty-four patients had severe CoA (PG >25 mmHg before stenting); baseline SBP was significantly higher in severe versus non-severe patients (160 mmHg vs. 148 mmHg; P=0.02). The absolute reduction in PG after stenting was significantly higher in the severe group (31 ± 7 mmHg vs. 14 ± 5 mmHg; P<0.0001), but there was no significant difference in SBP between groups at 6-12 weeks (141 mmHg vs. 135 mmHg; P=0.21) or 9-12 months (139 mmHg vs. 139 mmHg; P=0.96). CONCLUSION: Endovascular stenting of CoA results in a significant reduction in SBP at 6-12 weeks, which is sustained at 9-12 months, with similar outcomes in severe and non-severe CoA groups.

Dual Arterial Access for Stenting of Aortic Coarctation in Patients with Near-Total Descending Aortic Interruption.

Endovascular stenting is a recognized treatment strategy for the treatment of coarctation of aorta (COA) in adults. The aortic coarctation is usually crossed retrogradely from the descending aorta via the femoral approach. We report three patients who had near-total descending aortic interruption and underwent successful stenting of severe COA using a combined radial/brachial and femoral approach due to difficulty in crossing the lesion retrogradely via a femoral approach. There were no procedural complications and no adverse events during 6 months of follow-up.

Early diagnosis of cardiac implantable electronic device generator pocket infection using ¹8F-FDG-PET/CT.

AIMS: To examine the utility of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in the early diagnosis of cardiac implantable electronic device (CIED) generator pocket infection. METHODS AND RESULTS: A total of 86 patients with CIEDs were evaluated with (18)F-FDG PET/CT imaging: 46 with suspected generator pocket infection and 40 without any history of infection. (18)F-FDG activity in the region of the generator pocket was expressed as a semi-quantitative ratio (SQR)-defined as the maximum count rate around the CIED divided by the mean count rate between normal right and left lung parenchyma. All patients underwent standard clinical management, independent of the PET/CT result. Patients with suspected generator pocket infection that required CIED extraction (n = 32) had significantly higher (18)F-FDG activity compared with those that did not (n = 14), and compared with controls (n = 40) [SQR: 4.80 (3.18-7.05) vs. 1.40 (0.88-1.73) vs. 1.10 (0.98-1.40), respectively; P < 0.001]. On receiver operator characteristic analysis, SQR had a high diagnostic accuracy (area under curve = 0.98) for the early identification of patients with confirmed infection (i.e. those ultimately needing extraction)-with an optimal SQR cut-off value of >2.0 (sensitivity = 97%; specificity = 98%). CONCLUSION: This study highlights the potential benefits of evaluating patients with suspected CIED generator pocket infection using (18)F-FDG PET/CT. In this study, (18)F-FDG PET/CT had a high diagnostic accuracy in the early diagnosis of CIED generator pocket infection, even where initial clinical signs were underwhelming.

The effect of interleukin-1 receptor antagonist therapy on markers of inflammation in non-ST elevation acute coronary syndromes: the MRC-ILA Heart Study.

AIMS: Acute coronary syndromes (ACSs) are driven by inflammation within coronary plaque. Interleukin-1 (IL-1) has an established role in atherogenesis and the vessel-response to injury. ACS patients have raised serum markers of inflammation. We hypothesized that if IL-1 is a driving influence of inflammation in non-ST elevation ACS (NSTE-ACS), IL-1 inhibition would reduce the inflammatory response at the time of ACS. METHODS AND RESULTS: A phase II, double-blinded, randomized, placebo-controlled, study recruited 182 patients with NSTE-ACS, presenting <48 h from onset of chest pain. Treatment was 1:1 allocation to daily, subcutaneous IL-1receptor antagonist (IL-1ra) or placebo for 14 days. Baseline characteristics were well matched. Treatment compliance was 85% at 7 days. The primary endpoint (area-under-the-curve for C-reactive protein over the first 7 days) was: IL-1ra group, 21.98 mg day/L (95%CI 16.31-29.64); placebo group, 43.5 mg day/L (31.15-60.75) (geometric mean ratio = 0.51 mg/L; 95%CI 0.32-0.79; P = 0.0028). In the IL-1ra group, 14-day achieved high-sensitive C-reactive protein (P < 0.0001) and IL-6 levels (P = 0.02) were lower than Day 1. Sixteen days after discontinuation of treatment (Day 30) high-sensitive C-reactive protein levels had risen again in the IL-1ra group [IL-1ra; 3.50 mg/L (2.65-4.62): placebo; 2.21 mg/L (1.67-2.92), P = 0.022]. MACE at Day 30 and 3 months was similar but at 1 year there was a significant excess of events in the IL-1ra group. CONCLUSION: IL-1 drives C-reactive protein elevation at the time of NSTE-ACS. Following 14 days IL-1ra treatment inflammatory markers were reduced. These results show the importance of IL-1 as a target in ACS, but also indicate the need for additional studies with anti-IL-1 therapy in ACS to assess duration and safety. CLINICAL TRIAL REGISTRATION EUCTR: 2006-001767-31-GB: www.clinicaltrialsregister.eu/ctr-search/trial/2006-001767-31/GB.

Incidence and mechanisms of longitudinal stent deformation associated with Biomatrix, Resolute, Element, and Xience stents: Angiographic and case-by-case review of 1,800 PCIs.

BACKGROUND: There is conflicting evidence regarding the incidence of longitudinal stent deformation (LSD) in contemporary practice. METHODS AND RESULTS: To assess the incidence and mechanism of LSD across commonly used DES platforms, we performed a case-by-case review of 1,800 PCI cases involving 450 consecutive procedures using Biomatrix Flex, Resolute Integrity, Promus Element, and Xience V stents, respectively, between January 2009 and December 2011. LSD was detected in a higher proportion with Promus Element [15 (3.1%)] compared with other platforms (Xience V [4 (0.9%)], Biomatrix [3 (0.7%)], Resolute [3 (0.7%)]; P = 0.002). LSD was characterized as guide catheter/guide extension induced, or as impact from secondary devices such as postdilatation balloons or IVUS catheters. The incidence of guide catheter/guide extension LSD was similar across platforms; (Promus Element [5 (1.1%)], Xience V [4 (0.9%)], Biomatrix [3 (0.7%)], Resolute [3 (0.7%)]; P = 0.85). Secondary device LSD occurred exclusively with Promus Element (9/450 cases [2%] (P < 0.0001). Re-entering the deformed stent was more difficult in cases of secondary device LSD (6/9 compared with 0/12 treated cases; P < 0.001). Univariate predictors of LSD were previous CABG, culprit vessel, ostial involvement, and lesion tortuosity. Multivariate predictors of LSD were the Promus Element stent (OR 5.53 CI[1.54-19.85]), Guideliner use (OR 22.09 CI[4.73-103]), postdilation balloons (OR 5.47 CI[1.31-22.81]) and number of stents deployed (OR 2.06 CI[1.45-2.9]. CONCLUSION: LSD is more common than previously reported. LSD by a guide catheter/guide extension occurred equally with all platforms, however, LSD associated with secondary devices only occurred with the Element stent. These findings have important implications regarding current and future stent designs.

Pre-closure of Large-Sized Arterial Access Sites in Adults Undergoing Transcatheter Structural Interventions.

INTRODUCTION: Patients undergoing structural heart interventions often require large-sized sheath insertion into femoral arteries and veins. Clinical outcome data on the use of suture-mediated devices for large femoral arterial access in structural heart interventions is limited. We assessed the efficacy of the Perclose™ (Abbott Vascular Devices, Santa Clara, CA, USA) suture-mediated device using the pre-closure technique in achieving hemostasis in femoral arterial access sites following large sheath insertion (≥8 Fr). METHODS: One hundred consecutive patients underwent 101 femoral artery access sites closures with the Perclose device using the pre-closure technique. Sixty-two percent of the patients were male and their mean (SD) age was 52 (±26) years. All patients received heparin. RESULTS: Mean arterial access site sheath diameter was 13 ± 2 Fr. Immediate hemostasis was achieved in 96/101 (96%) procedures (≤2 min). Two patients (2%) had access site-related complications requiring further interventions. On clinical follow up [mean (SD) follow-up of 24 (±12) months and median follow-up of 8.5 months], no complications were seen in the arterial access sites. CONCLUSION: Pre-closure of large-size femoral arterial access sheath sites using the suture-mediated Perclose device is efficacious in achieving rapid hemostasis in patients undergoing structural interventions. On 1-year follow-up, there were no arterial access site complications requiring further investigations or interventions.

Risk stratification and hierarchy of antenatal care.

Cardiac disease is the leading cause of maternal death in the UK. The triennial maternal mortality reports have repeatedly highlighted failure to recognise the level of risk as a major contributing factor to the deaths of these women. Once the level of risk has been recognised, services then need to be organised in a way that supports the needs of the highest risk women, but avoids unnecessary intervention for women at lower risk. Risk scoring systems and lesion-specific indicators may help predict maternal and neonatal outcomes. Care can then be planned accordingly, to optimise the outcome for the woman and her baby.