Abstract
Crieff Hydro, Perthshire, Friday 13 & Saturday 14 November 2015
Percutaneous repair of paravalvular leak: The Edinburgh experience
1Clinical Research Fellow, University of Edinburgh, Edinburgh, UK
2Cardiologist, Royal Infirmary of Edinburgh, Edinburgh, UK
3Cardiologist, Royal Sussex County Hospital, Brighton, UK
Abstract
Background
Paravalvular leak (PVL) is a well-recognised complication following surgical valve replacement, affecting up to 10% of prosthetic valve implants.1,2 Many patients remain asymptomatic but they can present with heart failure, haemolytic anaemia and/or infective endocarditis. Until recently the treatment options were medical palliation or high-risk surgical re-operation. Over the past decade however, new techniques and devices have, in selected cases, made percutaneous closure of PVL a viable option.
Methods
We conducted a retrospective audit of all attempts at percutaneous repair of a PVL undertaken at the Edinburgh Heart Centre.
Results
Between April 2011 and May 2015 a total of 39 (15 female, 24 male) patients were treated and 44 procedures performed. The median age at time of procedure was 70 years (range 31–89). Heart failure was the most common primary indication for closure, accounting for 16 cases. Evidence of haemolysis was also present in 16 patients. All but one of the procedures was performed under general anaesthesia and employed transoesophageal echocardiographic guidance. The mitral valve (n = 26) was more commonly the target for intervention than the aortic valve (n = 16), whilst on two occasions both valves were treated. The devices implanted included the amplatzer vascular plug (AVP) type-2 (n = 1), AVP-3 (n = 43) and ventricular septal defect occluder (n = 4). The median length of stay following treatment was two days. Five patients required repeat procedures of which three were staged and two related to technical failure. Final procedural success, with clinically significant reduction in PVL severity, was achieved in 33 (85%) patients. One case of device embolisation was identified during follow-up and despite a further attempt at percutaneous repair this patient died from progressive heart failure. Other complications included femoral artery haemorrhage requiring vascular surgery (n = 1), an embolic stroke and persistent or recurrent PVL requiring subsequent surgical valve replacement (n = 2).
Conclusions
PVL is an important complication following prosthetic valve replacement. Percutaneous repair is feasible with a reasonably good chance of a successful outcome although repeat procedures may be necessary.
References
Molecular autopsy for sudden cardiac death – a multidisciplinary approach
1ST3, Aberdeen Royal Infirmary, Aberdeen
2Consultant Cardiologist, Aberdeen Royal Infirmary, Aberdeen
3Specialty Trainee in Clinical Genetics, NHS Grampian
4Specialty Trainee in Pathology, Department of Forensic Medicine, University of Aberdeen
5Principal Clinical Scientist, Medical Genetics, NHS Grampian
6Registered Genetic Counsellor, Clinical Genetics, NHS Grampian
7Senior Lecturer (Professor) of Pathology, University of Aberdeen
8Consultant Pathologist, NHS Highland
9Consultant Clinical Geneticist, NHS Grampian
Abstract
Aim
In Aberdeen, through a collaboration between genetics, forensic medicine and cardiology, a molecular autopsy has been undertaken in 95 cases of sudden cardiac death over the past 13 years. This audit was to determine the clinical effectiveness of our approach.
Methods
A retrospective analysis of cases of sudden death referred for molecular autopsy between January 2001 and December 2013.
Results
During the study period, 45 cases of sudden death between ages 1 and 40 had normal hearts and suspected arrhythmic death. Fifty cases aged between two and 67 had cardiomyopathy. 43/45 suspected arrhythmic deaths with normal hearts had genetic testing. All had long QT testing and eight were also tested for other conditions. Six pathogenic mutations (one KCNQ1, three KCNH2, one SCN5A and one RyR2) were detected. Among 50 cases of cardiomyopathy, 25 had arrhythmogenic right ventricular cardiomyopathy (ARVC), 10 dilated cardiomyopathy (DCM) and 15 hypertrophic cardiomyopathy (HCM). All had genetic testing. Eight pathogenic mutations were detected. Three ARVC cases had mutations in PKP2, DSC2 or DSP. Three HCM cases had MYBPC3 mutations and two DCM cases had mutation of MYH7. Uptake of cascade screening in relatives was higher when a molecular diagnosis was made at autopsy.
Conclusions
Despite a conservative approach to defining sequence variants as pathogenic, a molecular diagnosis was made in 13.6% of sudden arrhythmic and 16% of cardiomyopathy deaths. This illustrates the utility of careful use of new technology in the diagnosis of sudden cardiac death.
Biological ageing and coronary artery disease
1Clinical Senior Lecturer in Public Health. Public Health, Institute of Health and Wellbeing, University of Glasgow, UK
2Professor of Epigenetics, Institute of Cancer Sciences, University of Glasgow
3Professor of Cardiology. Director of Research, West of Scotland Regional Heart and Lung Centre. Golden Jubilee Hospital, Glasgow, UK
4Director of Institute Health and Wellbeing, University of Glasgow
Abstract
Introduction
Biological ageing is thought to vary between individuals of the same chronological age and increase susceptibility to ill health and disease. Therefore, biological ageing (‘miles on the clock’), rather than chronological ageing, may provide a better measurement of age-related risks and a more effective basis for clinical decision-making in relation to investigation and treatment in patients with coronary artery disease (CAD). A number of biomarkers of ageing have been explored, including telomere length. However, conflicting evidence exists as to whether leucocyte telomere length (LTL) is an appropriate biomarker of ageing in CAD.
Methods
A cross sectional study design was used to investigate the association between LTL (gene ratio – relative ratio of repeat to single copy number – T/S ratio) measured using qPCR (quantitative polymerase chain reaction) and CAD (its presence and severity) in 1846 consecutive patients attending a regional cardiovascular centre for coronary angiography.
Results
An inverse relationship was found between LTL T/S ratio and age. No statistically significant difference was found in mean T/S ratio between those with and without CAD (0.87(SD 0.21) versus 0.89(SD 0.21), p = 0.091), even after adjusting for baseline characteristics. In addition, there was no statistically significant difference in relative T/S length by severity of disease in those found to have stenosis on cardiac angiography: 0.875 (SD 0.211) versus 0.875 (SD 0.212) versus 0.860 (SD 0.203) versus 0.867 (SD 0.200), p = 0.670.
Conclusion
There is no evidence of an association between the presence and severity of CAD and the LTL T/S ratio. However, there is a need for follow-up of these participants to investigate whether LTL is associated with adverse outcomes in patients diagnosed with CAD. In addition, this cohort provides the opportunity of continuing to investigate emerging biomarkers of ageing in CAD, such as CDKN2A, Sirtuins 1 & 6, Fetuin A and phosphate.
Audit of implantable cardioverter defibrillator (ICD) shocks
Cardiology Department, Aberdeen Royal Infirmary, Aberdeen, UK
Abstract
Background
The implantable cardioverter defibrillator (ICD) is a proven lifesaving therapy for patients at risk of sudden cardiac death (SCD). The ICD is capable of monitoring the hearts activity delivering anti-tachycardia pacing therapy (ATP) and high energy shocks for the treatment of life-threatening ventricular arrhythmias. ICD shocks although lifesaving are painful, psychologically damaging, pro-arrhythmic, can result in deterioration in heart failure symptoms, increase mortality and shocks also deplete the ICD battery.1 The goal of the ICD is to deliver only deliver therapy to treat only arrhythmias that would lead to death. ICD shocks can be appropriate or inappropriate. Appropriate shocks are for the treatment of life-threatening arrhythmias and these shocks can be further subdivided into necessary (for arrhythmias that would lead to death) and unnecessary (for arrhythmias that would self-terminate or otherwise be treated by ATP). Inappropriate shocks are therapy delivered for any reason other than a ventricular arrhythmia (atrial fibrillation, sinus tachycardia, supraventricular tachycardia or external noise).2
Clinical audit
A retrospective clinical audit was performed of ICD patients followed up at Aberdeen Royal Infirmary (ARI) reviewing patient demographics, medications, device settings and shocks delivered. The audit included 364 patients and covered a 34-month period from January 2012 until October 2014. This audit period was selected to follow a period of significant change in programming practice and follow up by the cardiac rhythm management (CRM) team at ARI and follows on from a smaller audit in 2011.
Results
The ARI patient population are predominantly male (73.1%), with ischemic heart disease (55.5%). 45.9% of patients have a single chamber ICD, 29.4% have a dual chamber ICD and 24.7% have CRT-D systems. Appropriate and inappropriate shocks had occurred in 11.2 and 3.3% of patients, respectively, at 34 months. During this audit period, only one patient received a second inappropriate shock (7.7% one of 13 patients who received an inappropriate shock). The annual rate of appropriate shocks has remained relatively static over the audit periods (5.5–7%), while the annual rate of inappropriate shocks has fallen over the audit period (4% in 2011, 1.6% in 2012, 1.5% in 2013 and 0.9% in 2014).
Discussion
The ICD has the ability to prolong the life of the patient by significantly reducing their risk of sudden cardiac death but appropriate programming has the opportunity to reduce some of the morbidity and mortality3,4 associated with ICD shocks. The CRM team has taken an evidence-based approach to programming practice with the goal of reducing both appropriate and inappropriate shocks. This approach has allowed the CRM team to reduce its annual rate of inappropriate shocks from 4 to 0.9%. Real-world audits suggest that by 4–5 years, approximately 1/3 of ICD patients have experienced at least one shock episode with 16–18% receiving at least one inappropriate shock.5–7 ARI inappropriate shock rates are similar to the rates seen in MADIT-RIT over a similar duration,8 while the ARI population has a higher risk of inappropriate shocks. The number of patients receiving more than one episode of inappropriate shocks is also extremely low at 7.7% compared to published data that suggested that a patient who receives an inappropriate shock is likely to receive a further inappropriate shock (28% at one year and 55% at three years).3
References
Transradial catheterisation: a clinical translational model of human arterial injury in vivo
1Registrar/ Clinical research fellow, Centre for Cardiovascular Sciences, University of Edinburgh and Edinburgh Heart Centre, Edinburgh, UK
2Postdoctoral Scientist, Centre for Cardiovascular Sciences, University of Edinburgh, UK
3Consultant Cardiologist, Centre for Cardiovascular Sciences, University of Edinburgh and Edinburgh Heart Centre, Edinburgh, UK
Abstract
Introduction
Investigation of the role of circulating endothelial progenitor cells (EPCs) in human vascular repair has been limited by the lack of a safe and accessible model of human arterial injury in vivo. To address this, we characterised radial arterial injury and the EPC response in patients undergoing transradial cardiac catheterisation.
Methods
Patients undergoing elective angiography were enrolled (n = 21). Radial artery injury was assessed using optical coherence tomography (OCT). Arterial sheaths were examined for endothelial cells. Radial flow-mediated dilatation (FMD) was assessed bilaterally at baseline, 24 h, one, four and 12 weeks. Circulating EPCs were assessed at baseline and 24 h.
Results
Radial injury was observed in four patients (19%). Despite the low incidence of injury, FMD was attenuated in the catheterised versus non-catheterised artery at 24 h (4.31 ± 3.44 versus 10.74 ± 5.56 p = <0.05) and one week (3.10 ± 4.05 versus 7.65 ± 5.56 p = <0.05) but not at four and 12 weeks. Arterial sheaths yielded significant numbers of cells (mean 6.3 × 105 ± 4.65 × 105), a significant proportion of which were endothelial (40.0 ± 3.7%). Compared to baseline, transradial catheterisation was associated with significant mobilisation of CD34 + cells (0.05% ± 0.02 versus 0.09% ± 0.06 of mononuclear cells p < 0.05).
Conclusions
Transradial catheterisation is associated with endothelial denudation, radial artery vasomotor dysfunction and mobilisation of naïve progenitor cells, in the absence of vascular injury on OCT. The radial artery offers a unique model with which to examine arterial injury and therapies targeting cellular repair in vivo in man.
High-sensitivity cardiac troponin on presentation to rule out acute myocardial infarction
1Clinical research fellow, University of Edinburgh, Edinburgh, UK
2Cardiology registrar, NHS Lothian, Edinburgh
3Medical physician, NHS Lothian, Edinburgh
4Trial manager, University of Edinburgh, UK
5Clinical lecturer in Public Health, Centre of population health sciences, University of Edinburgh
6Clinical lecturer in Public Health, Centre of population health sciences, University of Edinburgh, UK
Abstract
Purpose
The majority of patients with chest pain do not have myocardial infarction and may be suitable for discharge directly from the Emergency Department. Whilst international guidelines recommend that troponin concentrations above the 99th centile be used to diagnose myocardial infarction, the optimal threshold to rule out myocardial infarction is uncertain. In a prospective trial, we aim to define the optimal threshold to rule out myocardial infarction on presentation in consecutive patients with suspected acute coronary syndrome.
Methods
Serum troponin concentrations were measured using a high-sensitivity troponin I assay in consecutive patients with suspected acute coronary syndrome, in this prospective multi-centred cohort. The primary outcome was an index diagnosis of myocardial infarction, and myocardial infarction or cardiac death at 30 days. Myocardial infarction was adjudicated based on the results from high-sensitivity troponin assay. We evaluated the negative predictive value (NPV) of a range of troponin concentrations to determine the optimal threshold to rule out myocardial infarction on presentation.
Results
We identified 4870 consecutive patients (age 64 ± 16 years, 57% men) who presented with suspected acute coronary syndrome. Myocardial infarction was diagnosed in 782 patients (16.1%) with 32 (0.7%) and 75 patients (1.5%) having myocardial infarction or cardiac death at 30 days, respectively. A troponin concentration < 5 ng/l on presentation had a NPV of 99.6% (95% confidence interval (CI) 99.4 T 99.9%) for the primary endpoint (Figure 1) and identified 2314 patients (48%) with a 3 T-fold lower risk of adverse cardiac events at one year than those where serial measurements < 99th percentile were used to rule out myocardial infarction (1% versus 3%; adjusted hazard ratio (95%CI) = 0.36 (0.19–0.69)) (Figure 2). The NPV of a troponin concentration < 5 ng/l on presentation was similar in men and women and when stratified by age (above and below 65 years old), history of coronary heart disease or absence of myocardial ischemia on the initial electrocardiogram (Figure 3).
Conclusions
Troponin concentrations < 5 ng/l on presentation correctly identified 2305 out of 2314 consecutive patients with suspected acute coronary syndrome who did not have myocardial infarction on serial testing or adverse cardiac events over the next 30 days. The NPV was 99.6% across the entire study population. Implementation of this approach would reduce hospital admissions and have major benefits for patients and healthcare providers.
Changes in forearm blood flow: Percentage change in forearm arterial blood flow to (a) Ucn 2 (3.6–36 pmol/min) and (b) Ucn 3 (360–3600 pmol/min) in patients with heart failure (red) and in healthy volunteers (black). (** = p < 0.01, * = p < 0.05). Substance P not shown. Changes in haemodynamic responses from baseline following systemic infusion (Protocol B). Hemodynamic responses to infusions of saline placebo (black), SNP (green), Ucn2 (red) and Ucn 3 (blue) in patients with heart failure and volunteers at Doses 1–3 (D1–D3). (**** = p < 0.0001, *** = p < 0.001, ** = p < 0.01, * = p < 0.05). Cumulative incidence of myocardial infarction or cardiac death in patients with troponin concentrations less than the 99th centile on serial measurements. Patients without index myocardial infarction were stratified into two groups based on the troponin concentration on presentation. Compared to those patients with troponin concentrations <5 ng/L (blue line) those patients with troponin concentrations >5 ng/L (red line) were 3-fold less likely to have a myocardial infarction or cardiac death at one year (1% versus 3%; HR [95%CI] = 0.36 [0.19 to 0.69], log rank P < 0.001).
Collaborative care with a pharmacist improves optimisation of secondary prevention medication after discharge in patients with left ventricular systolic dysfunction due to acute myocardial infarction
1Cardiology Registrar, Royal Alexandra Hospital, Paisley, UK
2Specialist Heart Failure Pharmacist, NHS Greater Glasgow and Clyde, Pharmacy & Prescribing Support Unit, Glasgow, UK
3Senior Pharmacist, NHS Greater Glasgow and Clyde, Pharmacy & Prescribing Support Unit, Glasgow, UK
4Consultant Cardiologist, Royal Alexandra Hospital, Paisley, UK
5Consultant Cardiologist, Golden Jubilee National Hospital, Glasgow, UK
6Professor of Cardiology, University of Glasgow, BHF Cardiovascular Research Centre, Glasgow, UK
Abstract
Purpose
Angiotensin-converting enzyme inhibitors (ACEIs), beta-blockers (BBs) and mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with left ventricular systolic dysfunction post-acute myocardial infarction (MI). We aimed to optimise the use of these drugs in such patients using a strategy of collaborating with a pharmacist at the time of hospital discharge.
Methods
Controlled before-and-after study. Patients with incident MI and echocardiographic left ventricular ejection fraction < 40% were included. Patients unable to return for cardiac rehabilitation (CR) after MIs were excluded. Two groups (1) retrospective ‘usual care’ patients identified through a database of admissions 08/2012 to 08/2013, (2) prospective ‘intervention’ patients identified during admission by CR nurses 08/2013 to 08/2014 and referred at the time of hospital discharge to CR in addition to a pharmacist clinic. The pharmacist prescribed in line with European Society of Cardiology (ESC) guidelines. Consultant Cardiologists provided clinical support.
Endpoints
Percentage of patients treated with, mean % target dose achieved of and % of patients on full ESC target dose of ACEI, BB and MRA four months after index MI discharge. Statistical significance was tested by Chi-squared and Mann–Whitney U tests.
Results
Fifty-seven ‘usual care’ and 51 ‘intervention’ patients were identified. There was no statistical difference in systolic blood pressure, heart rate or creatinine between groups; however, ‘usual care’ patients were significantly older than ‘intervention’ patients (67 versus 60 years, p = 0.014). The pharmacist reviewed ‘intervention’ patients a mean 4.6 times. Significantly more ‘intervention’ patients were treated with BB or MRA compared to ‘usual care’; 96.1% versus 82.5% (p = 0.025) and 49.0% versus 24.6% (p = 0.008), respectively. More ‘intervention’ compared to ‘usual care’ patients were treated with ACEI, this was not statistically significant; 94.1% versus 89.5% (p = 0.383). The mean dose of ACEI, BB and MRA (expressed as a % of ESC guideline target dose) was significantly higher in the ‘intervention’ compared to ‘usual care’ patients: 71.7% versus 43.8% (p < 0.0001), 55.9% versus 30.9% (p < 0.0001) and 35.3% versus 15.8% (p = 0.006), respectively. As was the proportion achieving full target dose of ACEI, BB and MRA: 56.9% versus 21.1% (p < 0.0001), 29.4% versus 7.0% (p = 0.002) and 21.6% versus 7.0% (p = 0.029), respectively.
Conclusion
Use of lifesaving therapy was improved significantly by the addition of collaborative care with a pharmacist. A randomised clinical trial is needed to assess the impact of such a service on patient outcomes.
Hepatic function as a prognostic tool to predict heart failure outcomes
1Clinical Research Fellow, Dept of Molecular and Clinical Medicine, School of Medicine, University of Dundee, UK
2Medical statistician, Dept of Molecular and Clinical Medicine, School of Medicine, University of Dundee, UK
3Professor of Cardiology, Dept of Molecular and Clinical Medicine, School of Medicine, University of Dundee, UK
Abstract
Introduction
Hepatic dysfunction has always been considered as a sequel of chronic heart failure (CHF); however, there has been recent interest in it being used as a marker of disease severity instead. Previous studies have demonstrated this among patients in clinical trial settings but no population-based studies have been conducted thus far. We aim to determine the impact of hepatic dysfunction on a composite of cardiovascular (CV) mortality and heart failure hospitalisation in patients treated for CHF.
Methods
We analysed data from the Systems BIOlogy Study to Tailored Treatment in Chronic Heart Failure (BIOSTAT-CHF) database which prospectively tracks treatment, co-morbidity, blood investigations, hospitalisation and death information of patients with heart failure from Tayside and Fife. Cox proportional hazard models were used to assess the prognostic impact of liver dysfunction on heart failure outcomes, while controlling for covariates like treatment regime, previous history of myocardial infarctions, atrial fibrillation, renal disease and CHF duration.
Results
Out of a total 1805 patients, there were 1200 (66.5%) males, with a mean age of 73.6 (± 10.7) years, and mean duration of HF 39.9 months with a total of 414 CV death or heart failure hospitalisation. We found low serum albumin levels (less than 30 g/l) to be an independent predictor of CV death or hospitalisation with a hazard ratio of 2.05 (95% CI 1.51–2.79, p < 0.001). Similarly, elevated bilirubin (more than 20 µmol/l) and alanine aminotransaminase (ALT) (more than 35 U/l) increased the risk of outcomes with hazards of 1.97 (95% CI 1.56–2.50, p < 0.001) and 1.31 (95% CI 1.04–1.66, p = 0.024), respectively.
Conclusions
Our findings demonstrate lower serum albumin, elevated total bilirubin and ALT were independent predictors of CV death or hospitalisation among ambulatory CHF patients. These markers can be easily used to risk stratify ambulatory CHF patients in the clinic.
A long-term observational study on surveillance and incidence of cardiotoxicity in breast cancer chemotherapy
1MSc Medicine Student, Department of Cardiovascular and Diabetes Medicine, University of Dundee – Ninewells Hospital and Medical School, UK
2Research fellow and cardiology registrar, Department of Cardiovascular and Diabetes Medicine, University of Dundee – Ninewells Hospital and Medical School, UK
3Medical Student, Department of Cardiovascular and Diabetes Medicine, University of Dundee – Ninewells Hospital and Medical School, Dundee, UK
4Consultant Oncologist, Oncology department, Ninewells Hospital, Dundee, UK
5Professor of Cardiology, Department of Cardiovascular and Diabetes Medicine, University of Dundee – Ninewells Hospital and Medical School, UK
Abstract
Introduction
Recent advances in chemotherapy have transformed breast cancer from a fatal disease to a survivable condition. However, many patients who survive their cancer succumb to the unintended adverse effects of therapy. Chemotherapy-induced cardiotoxicity is now among the most feared adverse effects and has been reported in up to 50% of patients up to 20 years later, the majority of which occurring after completion of therapy. Consequently, current breast cancer treatment guidelines recommend assessment of LV function before, during and after chemotherapy.
Methods
We conducted a retrospective cohort study of 1263 breast cancer patients who received either anthracyclines alone or combined with the monoclonal antibody trastuzumab at Ninewells Hospital, Dundee between January 2003 and December 2014. Imaging modalities such as MUGA scans were extracted from the CHEMOCARE database which allowed us to identify whether cardiac assessments were carried out at baseline and during treatment as per recommendations. LVEF at baseline and during routine follow-up was also calculated to determine if patients had developed left ventricular systolic dysfunction (LVSD) during chemotherapy.
Results
Of 1263 patients, two patients (0.2%) were male, with an average age of 53.5 years. 82.2% of the patients had received anthracyclines alone and 17.8% received a combination of an anthracycline and trastuzumab. A total of 683 (54.0%) underwent screening for baseline cardiac function using MUGA scans. Of these, only 290 (42.5%) had follow-up scans during the course of their treatment as mandated by guidelines. Among patients who had adequate follow up, 32 (11%) developed LVSD during chemotherapy, corresponding to a rate of 6.7% (n = 5) among those on anthracyclines alone and 12.5% (n = 27) among patients on combination therapy.
Conclusion
Our data shows despite recommendations to monitor cardiac function in all chemotherapy patients, only half of them were monitored in our cohort. Although LVSD is usually a late sequelae of cancer treatment, we have shown it occurring even during delivery of chemotherapy, thus underscoring the importance of surveillance to ensure early detection and management.
Cardiovascular effects of Urocortin 2 and Urocortin 3 in patients with heart failure and healthy volunteers
1Clinical Research Fellow, Centre for Cardiovascular Sciences, University of Edinburgh, UK
2Cardiology Clinical Lecturer, University of Glasgow, Glasgow, UK
3Professor of Cardiology, Centre for Cardiovascular Sciences, University of Edinburgh, UK
Abstract
Introduction
Urocortin 2 (Ucn 2) and Urocortin 3 (Ucn 3) may play a role in the pathophysiology and treatment of heart failure and are emerging therapeutic targets. We examined the local and systemic cardiovascular effects of both Ucn 2 and Ucn 3 in healthy subjects and patients with heart failure.
Methods
Local vascular study: Patients with heart failure (n = 8) and age and sex-matched healthy subjects (n = 8) underwent bilateral forearm arterial blood flow measurement using forearm venous occlusion plethysmography during intra-arterial infusions of Ucn 2 (3.6–36 pmol/min), Ucn 3 (360–3600 pmol/min) and substance P (control vasodilator, 2–8 pmol/min).
Systemic study: Patients with heart failure (n = 9) and healthy subjects (n = 7) underwent non-invasive impedance cardiography during incremental intravenous infusions of sodium nitroprusside (SNP, control vasodilator at 0.15/0.5/1.5 µg/kg/min), Ucn 2 (0.16/0.48/1.6 µg/min), Ucn 3 (5/15/50 µg/min) and placebo in a randomised double-blind, cross-over study.
Results
Vascular study: Ucn 2, Ucn 3 and substance P-induced dose-dependent forearm arterial vasodilatation (p < 0.05 for all, Figure 1). There was no difference in the magnitude of forearm arterial vasodilatation between patients and healthy controls (p > 0.05 for all agents).
Defining the optimal threshold to rule out myocardial infarction on presentation. a) Negative predictive value (NPV) of a range of troponin I concentrations on presentation for the composite outcome of index myocardial infarction, and myocardial infarction or cardiac death at 30 days; b) Proportion of patients with suspected acute coronary syndrome with troponin concentrations below each threshold.
Systemic study: Ucn 3 increased heart rate and cardiac index, and reduced mean arterial pressure and peripheral vascular resistance index in both healthy subjects and patients with heart failure (p < 0.05 for all). Ucn 2 had no effect on cardiac index in volunteers and heart rate in heart failure patients (p = 0.17, p = 0.1, respectively), but otherwise induced similar responses to Ucn 3 (p < 0.05 for all other hemodynamic parameters, Figure 2). In patients with heart failure, an exaggerated response to Ucn 3 was seen compared to Ucn 2.
Negative predictive value of troponin concentrations <5 ng/L on presentation stratified into subgroups. Negative predictive value (NPV) of troponin I concentrations <5 ng/L on presentation for the composite outcome of index myocardial infarction, and myocardial infarction or cardiac death at 30 days.
Conclusion
The acute forearm arterial vasodilator effects of Ucn 2 and 3 are preserved in patients with heart failure. Intravenous Ucn 2 and especially Ucn 3 increase cardiac output and reduce peripheral vascular resistance. This favourable hemodynamic profile suggests that Ucn 2 and Ucn 3 hold exciting therapeutic potential for the treatment of acute heart failure.