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Background: We compared the relationship between the third heart sound (S3) measured by an implantable cardiac device (devS3) and auscultation (ausS3) and evaluated their prognostic powers for predicting heart failure events (HFEs).Methods and Results: In the MultiSENSE study, devS3 was measured daily with continuous values, whereas ausS3 was assessed at study visits with discrete grades. They were compared among patients with and without HFEs at baseline and against each other directly. Cox proportional hazard models were developed between follow-up visits and over the whole study. Simulations were performed on devS3 to match the limitations of auscultation. We studied 900 patients, of whom 106 patients experienced 192 HFEs. Two S3 sensing modalities correlated with each other, but at baseline, only devS3 differentiated patients with or without HFEs (P < 0.0001). The prognostic power of devS3 was superior to that of ausS3 both between follow-up visits (HR = 5.7, P < 0.0001, and 1.7, P = 0.047, respectively) and over the whole study (HR = 2.9, P < 0.0001, and 1.4, P = 0.216, respectively). Simulation results suggested this superiority may be attributed to continuous monitoring and to subaudible measuring capability.Conclusions: S3 measured by implantable cardiac devices has stronger prognostic power to predict episodes of future HFEs than that of auscultation. [ABSTRACT FROM AUTHOR]

Background: Ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) can detect tissue-resident macrophage activity and identify cellular inflammation. Clinical studies using this technique are now emerging. We aimed to report a range of normal R2* values at 1.5 and 3 T in the myocardium and other tissues following ferumoxytol administration, outline the methodology used and suggest solutions to commonly encountered analysis problems. Methods: Twenty volunteers were recruited: 10 imaged each at 1.5 T and 3 T T2* and late gadolinium enhanced (LGE) MRI was conducted at baseline with further T2* imaging conducted approximately 24 h after USPIO infusion (ferumoxytol, 4 mg/kg). Regions of interest were selected in the myocardium and compared to other tissues. Results: Following administration, USPIO was detected by changes in R2* from baseline (1/T2*) at 24 h in myocardium, skeletal muscle, kidney, liver, spleen and blood at 1.5 T, and myocardium, kidney, liver, spleen, blood and bone at 3 T (p < 0.05 for all). Myocardial changes in R2* due to USPIO were 26.5 ± 7.3 s-1 at 1.5 T, and 37.2 ± 9.6 s-1 at 3 T (p < 0.0001 for both). Tissues showing greatest ferumoxytol enhancement were the reticuloendothelial system: the liver, spleen and bone marrow (216.3 ± 32.6 s-1, 336.3 ± 60.3 s-1, 69.9 ± 79.9 s-1; p < 0.0001, p < 0.0001, p = ns respectively at 1.5 T, and 275.6 ± 69.9 s-1, 463.9 ± 136.7 s-1, 417.9 ± 370.3 s-1; p < 0.0001, p < 0.0001, p < 0.01 respectively at 3 T). Conclusion: Ferumoxytol-enhanced MRI is feasible at both 1.5 Tand 3 T Careful data selection and dose administration, along with refinements to echo-time acquisition, post-processing and analysis techniques are essential to ensure reliable and robust quantification of tissue enhancement. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate whether late gadolinium enhancement (LGE) magnetic resonance imaging or N-terminal pro–B-type natriuretic peptide (NT-proBNP) could identify patients with a low risk of death or use of implantable cardioverter-defibrillator (ICD) in patients receiving a primary prevention ICD. Background: ICDs reduce mortality in patients with heart failure (HF), although two-thirds may never use their device. Current risk stratification, based on New York Heart Association functional class and left ventricular ejection fraction, still leads to implantation of ICDs in patients who may never need their device. Methods: We examined 157 patients with HF (61 with ischemic cardiomyopathy and 96 with dilated cardiomyopathy; mean age 50.5 years; 78% male) who underwent primary prevention defibrillator implantation. Presence and volume of LGE was measured before device implantation, and serum NT-proBNP level was measured before ICD implantation. The combined primary endpoint was cardiovascular death or appropriate ICD therapy (either appropriate shock or antitachycardia pacing). Results: The primary outcome occurred in 32 patients (20.4%) over a median follow-up period of 915 days. Percentage of LGE (hazard ratio [HR]: per 1% increase: 1.06; 95% confidence interval [CI]: 1.04 to 1.09; p < 0.001) and (ln) NT-proBNP (HR: 1.44; 95% CI: 1.04 to 1.98; p = 0.027) were predictors of death or appropriate ICD activation and remained significant when entered into multivariable analysis. When the cohort was stratified into tertiles based on LGE percentage and NT-proBNP, we were able to identify a low-risk group (event rate 3% per year, compared with the intermediate- and high-risk groups [6% and 10% per year, respectively]). Conclusions: Both percentage of LGE and NT-proBNP were associated with higher risk of death or appropriate ICD activation. The use of these markers in combination may be useful in identifying individuals most likely to benefit from this costly intervention, and more specifically, in the identification of a group at lower risk in whom ICD implantation may be deferred. [Copyright &y& Elsevier]

Abstract: Background: Anemia is prevalent in patients with chronic heart failure, the proportion of which increases with deteriorating New York Heart Association functional class. Anemia is also associated with increased symptoms, more frequent hospitalizations, and, in some studies, with an increased mortality rate. We have demonstrated that N-terminal brain natriuretic peptide (NT-proBNP) is a powerful predictor of death in advanced heart failure and is superior to the traditional markers of chronic heart failure (CHF) severity. However, to date, there are no published data that compare the prognostic ability of NT-proBNP with that of hemoglobin and hematocrit in patients with advanced heart failure who are referred for consideration of cardiac transplantation at a time when erythropoietin is under investigation as a treatment option in such a population. Methods and Results: We prospectively studied 182 consecutive patients with advanced CHF who had been referred for consideration of cardiac transplantation. Blood samples were taken at recruitment for routine investigation and for NT-proBNP analysis; the patients'' condition was followed for a median of 554 days. The primary end point of all-cause death was reached in 30 patients, and the secondary end point of all-cause death or urgent cardiac transplantation was reached in 34 patients. The mean hemoglobin level was 13.9 ± 2.2 g/dL, and the median concentration of NT-proBNP was 1505 pg/mL (interquartile range, 517–4015). The only multivariate predictor of all-cause death (χ2 =14.2; P < .001) or the secondary end point of all-cause death or urgent transplantation (χ2 =21.8; P < .001) was an NT-proBNP concentration above the median value. Conclusion: A single measurement of NT-proBNP in patients with advanced CHF can help to identify patients who are at a higher risk of death and is a better prognostic marker than anemia. [Copyright &y& Elsevier]

The ESC Guidelines recommend the measurement of N-terminal pro B-type natriuretic peptide (NT-proBNP) concentration in all patients who present to emergency rooms with acute dyspnoea and suspected acute decompensated heart failure (HF), with a decision cut-off (NT-proBNP<300pg/mL) for the exclusion of acute decompensated HF (ADHF). HeartLogic is a multisensor algorithm that has been developed and validated to proactively provide alerts for worsening heart failure. The purpose of this analysis was to compare the diagnostic accuracy of NT-proBNP and HeartLogic to rule out ADHF in acute settings. The MultiSENSE study followed 900 HF patients with implanted CRT-Ds for up to 1 year. All hospitalizations were adjudicated by an independent panel of clinicians, and classified as HF or non-HF based on the presenting cause. Optional NT-proBNP tests were conducted when patients were hospitalized. The composite HeartLogic index of the day before each of the hospitalization dates were extracted to differentiate HF and non-HF hospitalizations. By varying the HeartLogic index decision cutoff, a ROC curve was generated to assess the prediction accuracy of HeartLogic and compared to the counterpart performance of NT-proBNP using Hanley and McNeil's method. Of the total 603 hospitalizations, 76 hospitalizations (52 HF, 24 non-HF) had both valid NT-proBNP measures within 48 hours of admission (71 within 24 hours), and valid HeartLogic for the day before the hospitalization date. Figure 1 illustrates that the HeartLogic -based ROC was similar to the ROC of NT-proBNP (AUC of 0.809 and 0.803, respectively, p=0.932). An exclusion criterion of HeartLogic index <1 achieved the same performance as an NT-proBNP<300pg/ml (sensitivity 0.962, NPV 0.778), and the agreement between the two criteria was 84.2%. Limiting the evaluation to 52 hospitalizations with acute dyspnea (42 HF, 10 non-HF), the performance of HeartLogic and NT-proBNP were similar (p=0.906). Expanding the evaluation of HeartLogic across all 467 hospitalizations with HeartLogic data (89 HF, 378 non-HF), performance was still similar (sensitivity 0.934, NPV 0.876 for the criterion of HeartLogic index <1; AUC of 0.734, p=0.166). HeartLogic showed similar accuracy for differentiating HF and non-HF hospitalizations in the MultiSENSE dataset as NT-proBNP. HeartLogic may be used in the acute setting to exclude acute decompensated heart failure. [ABSTRACT FROM AUTHOR]

N-terminal pro-B-type natriuretic peptide (NT-proBNP), a non-active fragment of the prohormone proBNP, is produced by the heart and released in response to volume or pressure overload. NT-proBNP has proven to be a valuable biomarker in the diagnosis and prognosis of heart failure (HF), and NT-proBNP concentrations rise with worsening HF. HeartLogic, a multi-sensor composite index and alert algorithm, aggregates multiple physiologic trends associated with HF status, and proactively provides alerts for worsening HF with high sensitivity and low alert burden. To compare NT-proBNP concentrations during periods IN or OUT of an active HeartLogic alert. The MultiSENSE study enrolled 900 HF patients with an implanted COGNIS CRT-D, and followed them up to 1 year. Device software was modified to permit collection of chronic trends HeartLogic leveraged (heart sounds, heart rate, thoracic impedance, respiration and activity). Clinicians were blinded to individual sensors and results of HeartLogic during the study. Optional NT-proBNP tests were conducted when clinically needed (e.g., patients hospitalized with HF symptoms). HeartLogic index of the day before each of the NT-proBNP test dates was extracted. Based on HeartLogic alert state (i.e., IN alert vs OUT of alert), NT-proBNP concentrations were divided into two groups and compared using a one-way ANOVA. Of a total of 855 valid NT-proBNP tests in 741 patients with valid associated HeartLogic index, 180 NT-proBNP concentrations were measured in 150 patients while the HeartLogic alert state was IN alert, and 675 were measured in 616 patients while HeartLogic was OUT of alert. Figure 1 shows when HeartLogic was IN alert, the NT-proBNP concentrations (6957.9±10398.0 pg/ml) were significantly higher than those when HeartLogic was OUT of alert (1675.5±4403.1 pg/ml) (p<0.001), and the median NT-proBNP concentration was also higher (2224 pg/ml versus 561 pg/ml). HF patients' NT-proBNP concentrations were significantly elevated when HeartLogic was IN alert status, consistent with the HeartLogic algorithm capturing clinical worsening of HF status. [ABSTRACT FROM AUTHOR]