Jonathan R. Dalzell

Plasma apelin concentration is depressed following acute myocardial infarction in man.

Apelin, a novel peptide with a putative role in cardiovascular homeostasis, has gained interest as an endogenous inotrope, but has yet to be described following acute myocardial infarction (AMI) in man. We aimed to characterize plasma apelin concentrations following AMI and to examine its relationship with clinical and prognostic biomarkers.

The incremental prognostic and clinical value of multiple novel biomarkers in heart failure

In recent years there has been an increase in the number of biomarkers in heart failure (HF). The clinical role for these novel biomarkers in combination is not clear.

The Emerging Potential of the Apelin-APJ System in Heart Failure

The apelin-APJ system is a novel neurohormonal pathway, with studies to date suggesting that it may be of pathophysiologic relevance in heart failure and may indeed be a viable therapeutic target in this syndrome. This interest is driven primarily by the demonstration of its vasodilator, inotropic, and aquaretic actions as well as its apparent antagonistic relationship with the renin-angiotensin system. However, its promise is heightened further by the observation that, unlike other and more established cardioprotective pathways, it appears to be down-regulated in heart failure, suggesting that augmentation of this axis may have a powerful effect on the heart failure syndrome. We review the literature regarding the apelin-APJ system in heart failure and suggest areas requiring further research.

Profile of microvolt T-wave alternans testing in 1003 patients hospitalized with heart failure.

Observational studies in selected populations have suggested that microvolt T‐wave alternans (MTWA) testing may identify patients with heart failure (HF) at risk of sudden cardiac death. The aims of this study were to investigate the utility of MTWA testing in an unselected population of patients with HF and to evaluate the clinical characteristics associated with the MTWA results.

Congestive heart failure. Advances in management.

Arroll and colleagues’ review of the management of congestive heart failure1 disregards much of the progress made since the previous BMJ review of this topic in 2002.2 They concentrated on established pharmacotherapy …

Spectral microvolt T‐wave alternans testing has no prognostic value in patients recently hospitalized with decompensated heart failure

Microvolt T‐wave alternans (MTWA) testing identifies beat‐to‐beat fluctuations in T‐wave morphology, which have been linked to ventricular arrhythmias. However, clinical studies have produced conflicting results and data in heart failure (HF) have been limited. The aim of this study was to determine the prevalence and incremental prognostic value of spectral MTWA testing in an unselected cohort of patients recently hospitalized with HF.

The ease of use and reproducibility of the Alere™ Heart Check System: a comparison of patient and healthcare professional measurement of BNP.

AIMS The aim of the study was to examine the ease of use and the reproducibility of a novel point-of-care BNP measurement system when used by patients and healthcare providers (HCP). PATIENTS & METHODS Patients with symptomatic heart failure were recruited from outpatient clinics at four hospitals. They were provided with brief training and instructional material for the use of the point-of-care BNP measurement system. Finger-prick blood BNP concentration was measured by the HCP and the patient (n = 150). Ease of use and reproducibility of the system were assessed. RESULTS In total, 80% of the 164 patients who completed a questionnaire on the ease of use of the system found it easy to operate. There was excellent correlation of BNP measurement compared between patients and HCP (r = 0.966; p < 0.001). CONCLUSION Patients find the Alere Heart Check BNP measurement system easy to operate. BNP concentration measurements obtained by patients show excellent correlation with those obtained by healthcare providers.

Epinephrine Treatment of Anaphylaxis An Extraordinary Case of Very Late Acute Stent Thrombosis

78-year-old man experienced marked angioedema of his face and tongue following ingestion of chocolatecoated peanuts. Paramedics administered 0.5 mg of intramuscular epinephrine within half an hour of symptom onset with rapid relief of symptoms and subsidence of the swelling. On route to the local Emergency Department the patient suddenly became pale, nauseous, and began sweating profusely. There was no chest pain. Blood pressure was 182/105 and heart rate 107 beats per minute. An ECG revealed sinus tachycardia and marked anterior ST elevation (Figure 1), and he was urgently transferred to the regional interventional cardiology center. Aspirin 300 mg and clopidogrel 600 mg were administered before transfer. He had a significant history of coronary artery disease and 4 years previously had undergone percutaneous coronary intervention to the proximal left anterior descending (LAD) and proximal circumflex arteries with bare-metal stents. Three months following this he developed in-stent restenosis in the LAD stent that was treated by further percutaneous coronary intervention with 2 overlapping drug-eluting stents. He experienced infrequent exertional angina over the next 4 years and at the time of this presentation was taking aspirin 75 mg as a sole antiplatelet. There was no history of diabetes, noncompliance with aspirin therapy, or any other medical history suggestive of a hypercoagulable state. On arrival in the catherization laboratory 5000 IU heparin was administered intravenously. Coronary angiography showed a large dominant right system supplying collaterals to the circumflex artery. The LAD was occluded midway through the drug-eluting stents (Figure 2 and Supplemental Figure A). The circumflex was also blocked within the bare metal stent but was an unlikely culprit lesion given the anterior ECG changes, and the collateralization provided by the right coronary artery (RCA) to the level of the circumflex stent. A guide wire was passed to the distal LAD, the artery reopened and obvious focal clot visualized. Thrombus extraction, via an Export aspiration catheter, followed by balloon dilatation to high pressure restored TIMI 3 flow (Figure 3 and Supplemental Figure B) with complete resolution of the ECG changes (Figure 4). Surprisingly, there was no evidence of any significant in-stent restenosis and therefore no stent was deployed. Post-percutaneous coronary intervention medical care included glycoprotein IIb/IIIa inhibitor infusion and a recommendation for life-long dual antiplatelet therapy. The patient made an uncomplicated recovery and was provided with an epinephrine pen predischarge. In humans, exogenous epinephrine administration has been shown to promote platelet aggregation1 by increasing platelet production of thromboxane B2,2 heightening the sensitivity of platelets to ADP2 and promoting the thrombin induced binding of platelets to fibrinogen.3 Interestingly, platelets from angina patients are more sensitive to increased endogenous serum catecholamine levels, and thus more prone to aggregation compared with normal controls.4 Late and very late-stent thromboses are recognized complications of percutaneous coronary intervention occurring more than 30 days and 1 year, respectively, postprocedure. Discontinuation of antiplatelet therapy is the commonest factor associated with these rare complications. Factors known to be associated with stent thrombosis include, among others, left ventricular systolic dysfunction and index stenting in the setting of acute myocardial infarction, conditions that are both associated with increased circulating catecholamine levels. We believe that this is the first reported case of acute drug-eluting stents thrombosis induced by exogenous epinephrine administration. The lack of in-stent restenosis in the culprit drug-eluting stents makes this case all the more

Combined Free Light Chains Are Novel Predictors of Prognosis in Heart Failure.

OBJECTIVES This study investigated the prevalence and potential incremental prognostic value of combined free light chains (cFLCs) in patients recently hospitalized with decompensated heart failure (HF). BACKGROUND Inflammatory pathways are recognized in the pathogenesis and progression of HF. Free light chain (FLC) elevation is conventionally associated with monoclonal gammopathies, including multiple myeloma. Polyclonal increases in both kappa and lambda FLCs occur in autoimmune and other chronic inflammatory conditions. Recently, a novel assay for measuring kappa and lambda immunoglobulin FLCs together, known as combined free light chain (cFLC) has been developed. METHODS Six hundred twenty-eight patients recently hospitalized with decompensated HF were studied. cFLCs were measured by turbidimetry using an immunoassay. The incremental prognostic value of cFLCs for mortality was evaluated using Cox proportional hazard models including 22 established predictors of outcome in HF. RESULTS Of 628 patients, 290 (46%) died during a follow-up of 3.2 ± 1.5 years. Two hundred seventy patients (43%) had elevated cFLCs. There was a clear gradient in the risk of death according to cFLC quartile, with those in the top quartile having an unadjusted risk of mortality more than twice that of those in the lowest quartile (hazard ratio: 2.38; p < 0.0001). After multivariable analysis, cFLC remained an independent predictor of mortality, with an almost 50% higher adjusted risk for those in the top compared with bottom quartile. Older age, lower body mass index, New York Heart Association classification III/IV, previous myocardial infarction, current smoking and B-type natriuretic peptide, bilirubin, high-sensitivity C-reactive protein, glycated hemoglobin, and lymphocyte concentrations were also independent predictors of mortality. CONCLUSIONS cFLCs are an independent predictor of mortality in patients recently hospitalized with decompensated HF. Further work is required to assess the effects of HF therapies on cFLC concentrations and whether or not directly targeting this marker of inflammation improves prognosis for patients with HF.

Novel biomarkers in heart failure: an overview

Heart failure is a complex systemic syndrome resulting from significant impairment of cardiac function. A vast array of biological pathways is now known to be involved in heart failure, including deleterious pathways promoting its development and progression, as well as compensatory cardioprotective pathways. Some of the components of these pathways are now recognized as biomarkers of this condition, and can aid diagnosis, prognostication and guide management. As the understanding of the pathophysiology of heart failure progresses, further candidate biomarkers are being identified. This article reviews the literature regarding the more recently identified biomarkers and outlines areas requiring further study.