Targeting elevated left ventricular end-diastolic pressure following primary percutaneous coronary intervention for ST-segment elevation myocardial infarction - a phase one safety and feasibility study.

INTRODUCTION: Elevated left ventricular end diastolic pressure (LVEDP) is an independent predictor of mortality and heart failure in patients with ST-segment elevation myocardial infarction (STEMI). Whether lowering elevated LVEDP improves outcomes remains unknown. METHODS: This non-randomized, single blinded study with prospective enrolment and sequential group allocation recruited patients undergoing primary percutaneous coronary intervention for STEMI with LVEDP ⩾ 20 mmHg measured immediately after primary percutaneous coronary intervention. The intervention arm (n=10) received furosemide 40 mg intravenous bolus plus escalating doses of glyceryl trinitrate (100 µg per min to a maximum of 1000 µg) during simultaneous measurement of LVEDP. The control group (n=10) received corresponding normal saline boluses with simultaneous measurement of LVEDP (10 readings over 10 min). Efficacy endpoints were final LVEDP achieved, and the dose of glyceryl trinitrate needed to reduce LVEDP by ⩾ 20%. Safety endpoint was symptomatic hypotension (systolic blood pressure < 90 mmHg). RESULTS: From 1 April 2017 to 23 August 2017 we enrolled 20 patients (age: 64±9 years, males: 60%, n=12, anterior STEMI: 65%, n=13). The mean LVEDP for the whole cohort (n=20) was 29±4 mmHg (intervention group: 28±3 mmHg vs. control group: 31±5 mmHg; p=0.1). The LVEDP dropped from 28±3 to 16±2 mmHg in the glyceryl trinitrate + furosemide group (p <0.01) but remained unchanged in the control group. The median dose of glyceryl trinitrate required to produce ⩾ 20% reduction in LVEDP in the intervention group was 200 µg (range: 100-800). One patient experienced asymptomatic decline in systolic blood pressure to below 90 mmHg. There was no correlation between LVEDP and left ventricular ejection fraction. CONCLUSION: The administration of glyceryl trinitrate plus furosemide in patients with elevated LVEDP following primary percutaneous coronary intervention for STEMI safely reduces LVEDP.

Behavioural activation therapy for post-stroke depression: the BEADS feasibility RCT.

BACKGROUND: There is currently insufficient evidence for the clinical effectiveness and cost-effectiveness of psychological therapies for post-stroke depression. OBJECTIVE: To evaluate the feasibility of undertaking a definitive trial to evaluate the clinical effectiveness and cost-effectiveness of behavioural activation (BA) compared with usual stroke care for treating post-stroke depression. DESIGN: Parallel-group, feasibility, multicentre, randomised controlled trial with nested qualitative research and a health economic evaluation. SETTING: Acute and community stroke services in three sites in England. PARTICIPANTS: Community-dwelling adults 3 months to 5 years post stroke who are depressed, as determined by the Patient Health Questionnaire-9 (PHQ-9) or the Visual Analogue Mood Scales 'Sad' item. Exclusions: patients who are blind and/or deaf, have dementia, are unable to communicate in English, do not have mental capacity to consent, are receiving treatment for depression at the time of stroke onset or are currently receiving psychological intervention. RANDOMISATION AND BLINDING: Participants were randomised (1 : 1 ratio) to BA or usual stroke care. Randomisation was conducted using a computer-generated list with random permuted blocks of varying sizes, stratified by site. Participants and therapists were aware of the allocation, but outcome assessors were blind. INTERVENTIONS: The intervention arm received up to 15 sessions of BA over 4 months. BA aims to improve mood by increasing people's level of enjoyable or valued activities. The control arm received usual care only. MAIN OUTCOME MEASURES: Primary feasibility outcomes concerned feasibility of recruitment to the main trial, acceptability of research procedures and measures, appropriateness of baseline and outcome measures, retention of participants and potential value of conducting the definitive trial. Secondary feasibility outcomes concerned the delivery of the intervention. The primary clinical outcome 6 months post randomisation was the PHQ-9. Secondary clinical outcomes were Stroke Aphasic Depression Questionnaire - Hospital version, Nottingham Leisure Questionnaire, Nottingham Extended Activities of Daily Living, Carer Strain Index, EuroQol-5 Dimensions, five-level version and health-care resource use questionnaire. RESULTS: Forty-eight participants were recruited in 27 centre-months of recruitment, at a recruitment rate of 1.8 participants per centre per month. The 25 participants randomised to receive BA attended a mean of 8.5 therapy sessions [standard deviation (SD) 4.4 therapy sessions]; 23 participants were allocated to usual care. Outcome assessments were completed by 39 (81%) participants (BA, n = 18; usual care, n = 21). Mean PHQ-9 scores at 6-month follow-up were 10.1 points (SD 6.9 points) and 14.4 points (SD 5.1 points) in the BA and control groups, respectively, a difference of -3.8 (95% confidence interval -6.9 to -0.6) after adjusting for baseline PHQ-9 score and centre, representing a reduction in depression in the BA arm. Therapy was delivered as intended. BA was acceptable to participants, carers and therapists. Value-of-information analysis indicates that the benefits of conducting a definitive trial would be likely to outweigh the costs. It is estimated that a sample size of between 580 and 623 participants would be needed for a definitive trial. LIMITATIONS: Target recruitment was not achieved, although we identified methods to improve recruitment. CONCLUSIONS: The Behavioural Activation Therapy for Depression after Stroke trial was feasible with regard to the majority of outcomes. The outstanding issue is whether or not a sufficient number of participants could be recruited within a reasonable time frame for a definitive trial. Future work is required to identify whether or not there are sufficient sites that are able to deliver the services required for a definitive trial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN12715175. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 47. See the NIHR Journals Library website for further project information.

Approximately one-third of stroke patients experience depression, which can have negative effects on recovery and quality of life (QoL). Currently, we do not have sufficient evidence to indicate which psychological interventions are effective and affordable to the NHS for treating post-stroke depression. We aimed to determine whether or not it is feasible to conduct a future large-scale study to evaluate a psychological intervention, called behavioural activation (BA) therapy, for treating post-stroke depression. BA aims to improve mood by identifying what stroke patients enjoy doing and helping them to undertake these activities. BA can be used with all stroke patients with depression, including people with cognitive or communication difficulties. We recruited 48 post-stroke patients who had suffered a stroke between 3 months and 5 years previously. People with dementia or significant aphasia were excluded. Participants were divided into two groups at random. About half of the participants received BA over a 4-month period and the other half did not. Participants received all other available care. After 6 months, participants completed questionnaires about their mood, activity level and QoL. We also interviewed 16 participants and 10 carers about their views on the actual research process and therapy. Although we were able to recruit participants to the study, we recruited fewer than the original target of 72 participants owing to delays in starting recruitment. However, we have identified ways to improve participant recruitment in a future study. We found that it was feasible to deliver BA, and the therapy was found to be acceptable to participants, carers and therapists. The results indicate that the benefits of conducting a large-scale future study would outweigh the costs. However, the main consideration will be whether or not we could identify enough stroke services able to run the study for a long enough period to recruit the large number of participants required.

Efficacy and cost-effectiveness of nurse-led care involving education and engagement of patients and a treat-to-target urate-lowering strategy versus usual care for gout: a randomised controlled trial.

BACKGROUND: In the UK, gout management is suboptimum, with only 40% of patients receiving urate-lowering therapy, usually without titration to achieve a target serum urate concentration. Nurses successfully manage many diseases in primary care. We compared nurse-led gout care to usual care led by general practitioners (GPs) for people in the community. METHODS: Research nurses were trained in best practice management of gout, including providing individualised information and engaging patients in shared decision making. Adults who had experienced a gout flare in the previous 12 months were randomly assigned 1:1 to receive nurse-led care or continue with GP-led usual care. We assessed patients at baseline and after 1 and 2 years. The primary outcome was the percentage of participants who achieved serum urate concentrations less than 360 µmol/L (6 mg/dL) at 2 years. Secondary outcomes were flare frequency in year 2, presence of tophi, quality of life, and cost per quality-adjusted life-year (QALY) gained. Risk ratios (RRs) and 95% CIs were calculated based on intention to treat with multiple imputation. This study is registered with www.ClinicalTrials.gov, number NCT01477346. FINDINGS: 517 patients were enrolled, of whom 255 were assigned nurse-led care and 262 usual care. Nurse-led care was associated with high uptake of and adherence to urate-lowering therapy. More patients receiving nurse-led care had serum urate concentrations less than 360 µmol/L at 2 years than those receiving usual care (95% vs 30%, RR 3·18, 95% CI 2·42-4·18, p<0·0001). At 2 years all secondary outcomes favoured the nurse-led group. The cost per QALY gained for the nurse-led intervention was £5066 at 2 years. INTERPRETATION: Nurse-led gout care is efficacious and cost-effective compared with usual care. Our findings illustrate the benefits of educating and engaging patients in gout management and reaffirm the importance of a treat-to-target urate-lowering treatment strategy to improve patient-centred outcomes. FUNDING: Arthritis Research UK.

Sleep-Disordered Breathing in Patients with Pulmonary Valve Incompetence Complicating Congenital Heart Disease.

OBJECTIVE: Long standing pulmonary regurgitation results in deleterious effects on right heart size and function with late consequences of right heart volume overload including ventricular dilatation, propensity to arrhythmia and right heart failure. As sleep disordered breathing may predispose to elevations in pulmonary vascular resistance and associated negative effects on right ventricular function, we sought to assess this in patients with underlying congenital heart disease. DESIGN: We performed a pilot study to evaluate the incidence of sleep-disordered breathing in a patient population with a history of long standing pulmonary valve incompetence in patients with congenital heart disease using overnight oximetry. PATIENTS: Patients with a background of tetralogy of Fallot repair or residual pulmonary incompetence following previous pulmonary valve intervention for congenital pulmonary stenosis were included. RESULTS: Twenty-two patients underwent overnight oximetry. The mean age of the cohort was 34.3 ± 15.2 years with no patients observed to have severe underlying pulmonary hypertension. Abnormal overnight oximetry was seen in 13/22 patients (59.1%) with 2/22 (9.1%) patients considered to have severe abnormalities. CONCLUSIONS: An important proportion of patients with a background of pulmonary incompetence complicating congenital heart disease are prone to the development of sleep-disordered breathing as assessed by overnight oximetry. Further study into the prevalence and mechanisms of sleep-disordered breathing in a larger cohort are warranted.

Association between drug-eluting stent type and clinical outcomes in patients with chronic kidney disease undergoing percutaneous coronary intervention.

BACKGROUND: The comparative efficacy of first- vs second-generation drug-eluting stents (DESs) in patients with chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI) is unknown. METHODS: A retrospective analysis of consecutive patients undergoing PCI at a tertiary PCI center from 2007-2011 was performed, with linkage to administrative databases for long-term outcomes. CKD was defined as creatinine clearance (CrCl) < 60 mL/min. Propensity matching by multivariable scoring method and Kaplan-Meier analyses were performed. RESULTS: Of 6481 patients with available CrCl values undergoing a first PCI during the study period, 1658 (25%) had CKD. First- and second-generation DESs were implanted in 320 (19.3%) and 128 (7.7%) patients with CKD, respectively. At 2 years, no significant differences were observed between first-generation (n = 126) and second-generation (n = 126) propensity-matched DES cohorts for the outcomes of death (19% vs 16%; P = 0.51), repeat revascularization (10% vs 10%; P = 1.00), and major adverse cardiovascular and cerebrovascular events (MACCE) (36% vs 37%; P = 0.90). The 2-year Kaplan-Meier survival was also similar (P = 0.77). In patients with CKD, second-generation DES type was not an independent predictor for death (P = 0.49) or MACCE (P = 1.00). CONCLUSIONS: Although the use of first- and second-generation DESs was associated with similar 2-year safety and efficacy in patients with CKD, our results cannot rule out a beneficial effect of second- vs first-generation DESs owing to small sample size. Future studies with larger numbers of patients with CKD are needed to identify optimal stent types, which may improve long-term clinical outcomes.

Percutaneous device closure of patent foramen ovale using the Premere occlusion device: initial experience, procedural, and intermediate-term results.

BACKGROUND: Percutaneous device closure is a therapeutic option in patients with presumed stroke complicating paradoxical emboli. Newer devices with lower profiles and potentially reduced thrombogenicity have emerged, such as the Premere PFO occlusion device (St Jude Medical, Inc.); there are limited data on the efficacy and procedural experience with this device. METHODS: We evaluated our initial experience with the Premere device in a contemporary patient cohort, comparing the procedural and intermediate follow-up characteristics with the currently utilized Amplatzer PFO occluder. RESULTS: Both devices were similarly effective in terms of immediate procedural success and defect closure. Procedures using the Premere device tended to be longer and required larger vascular access-sheath sizes; there were also significantly more adverse events in the Premere group (4/29) compared to the Amplatzer group (0/42; P=.02), including 1 retroperitoneal bleed, 2 hematomas, and 1 myocardial infarction. CONCLUSIONS: While the Amplatzer device may offer advantages in terms of safety and procedural simplicity, this in part reflects the early procedural experience with this new device. The Premere and Amplatzer PFO occlusion devices are similarly effective in achieving PFO closure when applied to appropriate anatomy and should be considered complementary when performing such procedures.

Cardiac risks and management of complications in pregnant women with congenital heart disease.

There are a growing number of women with congenital heart disease reaching adulthood and contemplating and/or undergoing pregnancy. However, pregnancy imposes hemodynamic stress on the heart and this can result in maternal, fetal and neonatal complications. Most women with congenital heart disease do well during pregnancy, but some women with high-risk cardiac lesions will not tolerate the hemodynamic changes of pregnancy. Physicians must be aware of the potential risks for the mother both during and after pregnancy, the risks to the fetus and neonate, and the risks and benefits of medications and procedures used during pregnancy. For women with complex cardiac conditions, management during pregnancy benefits from multidisciplinary care involving cardiologists with expertise in pregnancy, obstetricians with expertise in maternal fetal medicine, neonatologists and obstetric anesthetists, among others. This review will focus on the cardiac risks faced by women with congenital heart disease; particularly those at high risk, and on management strategies to mitigate risk and address cardiac complications.

Stroke during pregnancy: therapeutic options and role of percutaneous device closure.

Percutaneous device closure of patent foramen ovale has developed into a therapeutic option for patients with presumed cryptogenic stroke. The appropriate use of these therapies relies on appropriate clinical assessment, as well as an understanding of the potential advantages of certain closure devices. Pregnancy is an uncommon scenario for stroke, but nonetheless represents a hypercoaguable state which may predispose to thromboembolism. We describe a case of stroke during pregnancy treated with percutaneous device closure; the role of, and alternatives to, device closure are discussed, as are specific issues related to device selection and the interventional procedure.

Influence of age on long-term outcome after emergent percutaneous coronary intervention for ST-elevation myocardial infarction.

BACKGROUND: Percutaneous coronary intervention (PCI) provides advantages compared to thrombolytic therapy in the treatment of ST-elevation myocardial infarction (STEMI). Elderly patients have increased in-hospital mortality; the predictors of adverse outcomes are not well established, with limited data available regarding late follow up of these patients. We evaluated early and late outcomes of patients undergoing emergent PCI for STEMI to identify the predictors of subsequent late adverse events and, in particular, determine if age alone was a predictor of an adverse outcome. MATERIALS AND METHODS: A retrospective review of all patients referred for emergent PCI for STEMI to a single tertiary referral center was performed. All patients undergoing primary PCI for STEMI or rescue PCI for failed thrombolysis between December 2003 and December 2007 were included for assessment. RESULTS: During the study period, 269 patients underwent primary or rescue PCI for STEMI. Patients > or = 70 years of age were more likely to have established cardiovascular risk factors and documented coronary artery disease. Thrombolysis in myocardial infarction (TIMI) 3 flow predicted a good outcome, whereas recurrent ischemia in hospital, prior aspirin therapy and discharge creatinine predicted a poor outcome; age alone was not an adverse prognostic factor. CONCLUSIONS: The increased mortality in elderly patients undergoing PCI for STEMI reflects comorbidity and suboptimal procedural outcomes rather than any age effect per se. Future approaches to optimize the management of STEMI in the elderly should include identification of those patients most likely to benefit from an invasive approach.