Colette E. Jackson

Albuminuria in chronic heart failure: prevalence and prognostic importance

BACKGROUND Increased excretion of albumin in urine might be a marker of the various pathophysiological changes that arise in patients with heart failure. Therefore our aim was to assess the prevalence and prognostic value of a spot urinary albumin to creatinine ratio (UACR) in patients with heart failure. METHODS UACR was measured at baseline and during follow-up of 2310 patients in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) Programme. The prevalence of microalbuminuria and macroalbuminuria, and the predictive value of UACR for the primary composite outcome of each CHARM study--ie, death from cardiovascular causes or admission to hospital with worsening heart failure--and death from any cause were assessed. FINDINGS 1349 (58%) patients had a normal UACR, 704 (30%) had microalbuminuria, and 257 (11%) had macroalbuminuria. The prevalence of increased UACR was similar in patients with reduced and preserved left ventricular ejection fractions. Patients with an increased UACR were older, had more cardiovascular comorbidity, worse renal function, and a higher prevalence of diabetes mellitus than did those with normoalbuminuria. However, a high prevalence of increased UACR was still noted among patients without diabetes, hypertension, or renal dysfunction. Elevated UACR was associated with increased risk of the composite outcome and death even after adjustment for other prognostic variables including renal function, diabetes, and haemoglobin A1c. The adjusted hazard ratio (HR) for the composite outcome in patients with microalbuminuria versus normoalbuminuria was 1.43 (95% CI 1.21-1.69; p<0.0001) and for macroalbuminuria versus normoalbuminuria was 1.75 (1.39-2.20; p<0.0001). The adjusted values for death were 1.62 (1.32-1.99; p<0.0001) for microalbuminuria versus normoalbuminuria, and 1.76 (1.32-2.35; p=0.0001) for macroalbuminuria versus normoalbuminuria. Treatment with candesartan did not reduce or prevent the development of excessive excretion of urinary albumin. INTERPRETATION Increased UACR is a powerful and independent predictor of prognosis in heart failure. FUNDING AstraZeneca.

Is Microvolt T-Wave Alternans the Answer to Risk Stratification in Heart Failure?

Despite recent advances in the prevention and treatment of cardiovascular disease, sudden cardiac death (SCD) still accounts for ≈50% of all cardiovascular deaths in developed countries, thus accounting for a significant proportion of annual death worldwide.1 Reduction of the incidence of SCD depends on identification of those at most risk. In the present review we will concentrate on the challenges of risk stratification for SCD in chronic heart failure (CHF). We evaluate the utility of microvolt T-wave alternans (MTWA) as a tool for predicting SCD and consider whether MTWA is currently a valid means of selecting which patients should, or should not, receive an implantable cardioverter-defibrillator (ICD). Until recently, attempts to prevent SCD relied on pharmacological therapy. β-Blockers,2 angiotensin-converting enzyme inhibitors,3 angiotensin receptor blockers4 and aldosterone antagonists5 modestly reduce the risk of SCD in patients with CHF and after myocardial infarction (MI), whereas antiarrhythmic therapy has largely failed.6 Despite such treatments, these patients remained at high risk until the advent of the ICD. Although ICDs have further reduced the risk of SCD, they are expensive and can be associated with significant morbidity; therefore, precisely targeting their use is crucial. Implantation of ICDs for secondary prevention is clear. Prior sustained ventricular arrhythmia confers high risk and the benefit/risk balance is clearly favorable.7 Also, the secondary prevention population is relatively small and readily identified, thus the financial costs are not insurmountable. Primary prevention ICD therapy is an entirely different scenario. Large, randomized controlled trials have shown a mortality benefit with ICDs in patients with a low left ventricular ejection fraction (LVEF) and a history of MI or CHF.6,8 However, 2 major concerns have restricted implementation of this strategy. First, although analyses have estimated an acceptable cost-effectiveness profile,9 the immediate cost of implanting devices …

Differing prognostic value of pulse pressure in patients with heart failure with reduced or preserved ejection fraction: results from the MAGGIC individual patient meta-analysis

AIMS Low pulse pressure is a marker of adverse outcome in patients with heart failure (HF) and reduced ejection fraction (HF-REF) but the prognostic value of pulse pressure in patients with HF and preserved ejection fraction (HF-PEF) is unknown. We examined the prognostic value of pulse pressure in patients with HF-PEF [ejection fraction (EF) ≥ 50%] and HF-REF. METHODS AND RESULTS Data from 22 HF studies were examined. Preserved left ventricular ejection fraction (LVEF) was defined as LVEF ≥ 50%. All-cause mortality at 3 years was evaluated in 27 046 patients: 22 038 with HF-REF (4980 deaths) and 5008 with HF-PEF (828 deaths). Pulse pressure was analysed in quintiles in a multivariable model adjusted for the previously reported Meta-Analysis Global Group in Chronic Heart Failure prognostic variables. Heart failure and reduced ejection fraction patients in the lowest pulse pressure quintile had the highest crude and adjusted mortality risk (adjusted hazard ratio 1.68, 95% confidence interval 1.53-1.84) compared with all other pulse pressure groups. For patients with HF-PEF, higher pulse pressure was associated with the highest crude mortality, a gradient that was eliminated after adjustment for other prognostic variables. CONCLUSION Lower pulse pressure (especially <53 mmHg) was an independent predictor of mortality in patients with HF-REF, particularly in those with an LVEF < 30% and systolic blood pressure <140 mmHg. Overall, this relationship between pulse pressure and outcome was not consistently observed among patients with HF-PEF.

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.

Associations of albuminuria in patients with chronic heart failure: findings in the ALiskiren Observation of heart Failure Treatment study.

To examine the relationships between baseline characteristics and urinary albumin excretion in the extensively phenotyped patients in the ALiskiren Observation of heart Failure Treatment (ALOFT) study.

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.

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.

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.