Brachial pulse pressure in acute heart failure. Results of the Heart Failure Registry.

AIMS: To investigate the still uncertain independent prognostic impact of pulse pressure (PP) in acute heart failure (HF), in particular across the left ventricular ejection fraction (EF) phenotypes, and the potential contribution of PP in outlining the individual phenotypes. METHODS AND RESULTS: We prospectively evaluated 1-year death and rehospitalization in 4314 patients admitted for acute HF grouped by EF and stratified by their PP level on admission. In HF with reduced (< 40%) EF (HFrEF), the highest quartiles of PP had the lowest unadjusted [hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.61-0.98] and adjusted (HR 0.64 0.50-0.82) risk of 1 year all cause death compared to the lowest quartile. Its prognostic impact was partially mediated by systolic blood pressure (SBP). In HF with preserved (≥ 50%) EF (HFpEF), the intermediate quartile of PP showed the lowest 1 year all cause mortality in unadjusted (HR 0.598, CI 0.416-0.858) and adjusted (HR 0.55, 95% CI 0.388-0.801) models with no relationship with SBP. In a receiver operating characteristic analysis, a combination of PP > 60 mmHg and SBP > 140 mmHg was associated to a preserved EF with a high performance value. No prognostic significance of PP was found in the HF with mid-range EF subgroup. CONCLUSIONS: In acute HFrEF, there is an almost linear inverse relation between mortality and PP, partly mediated by SBP. In HFpEF, a J-shaped relationship between mortality and PP was present with a better prognosis at the nadir. A combination of PP > 60 mmHg with SBP > 140 mmHg may be clinically helpful as marker of a preserved left ventricular EF.

Natriuretic peptide-guided management in heart failure.

Heart failure is a clinical syndrome that manifests from various cardiac and noncardiac abnormalities. Accordingly, rapid and readily accessible methods for diagnosis and risk stratification are invaluable for providing clinical care, deciding allocation of scare resources, and designing selection criteria for clinical trials. Natriuretic peptides represent one of the most important diagnostic and prognostic tools available for the care of heart failure patients. Natriuretic peptide testing has the distinct advantage of objectivity, reproducibility, and widespread availability.The concept of tailoring heart failure management to achieve a target value of natriuretic peptides has been tested in various clinical trials and may be considered as an effective method for longitudinal biomonitoring and guiding escalation of heart failure therapies with overall favorable results.Although heart failure trials support efficacy and safety of natriuretic peptide-guided therapy as compared with usual care, the relationship between natriuretic peptide trajectory and clinical benefit has not been uniform across the trials, and certain subgroups have not shown robust benefit. Furthermore, the precise natriuretic peptide value ranges and time intervals of testing are still under investigation. If natriuretic peptides fail to decrease following intensification of therapy, further work is needed to clarify the optimal pharmacologic approach. Despite decreasing natriuretic peptide levels, some patients may present with other high-risk features (e.g. elevated troponin). A multimarker panel investigating multiple pathological processes will likely be an optimal alternative, but this will require prospective validation.Future research will be needed to clarify the type and magnitude of the target natriuretic peptide therapeutic response, as well as the duration of natriuretic peptide-guided therapy in heart failure patients.

Epidemiology, pathophysiology, and in-hospital management of pulmonary edema: data from the Romanian Acute Heart Failure Syndromes registry.

AIM: The objective of this study was to evaluate the clinical presentation, inpatient management, and in-hospital outcome of patients hospitalized for acute heart failure syndromes (AHFS) and classified as pulmonary edema (PE). METHODS: The Romanian Acute Heart Failure Syndromes (RO-AHFS) study was a prospective, national, multicenter registry of all consecutive patients admitted with AHFS over a 12-month period. Patients were classified at initial presentation by clinician-investigators into the following clinical profiles: acute decompensated HF, cardiogenic shock, PE, right HF, or hypertensive HF. RESULTS: RO-AHFS enrolled 3224 patients and 28.7% (n = 924) were classified as PE. PE patients were more likely to present with pulmonary congestion, tachypnea, tachycardia, and elevated systolic blood pressure and less likely to have peripheral congestion and body weight increases. Mechanical ventilation was required in 8.8% of PE patients. PE patients received higher doses (i.e. 101.4 ±â€Š27.1 mg) of IV furosemide for a shorter duration (i.e. 69.3 ±â€Š22.3 hours). Vasodilators were given to 73.6% of PE patients. In-hospital all-cause mortality (ACM) in PE patients was 7.4%, and 57% of deaths occurred on day one. Increasing age, concurrent acute coronary syndromes, life-threatening ventricular arrhythmias, elevated BUN, left bundle branch block, inotrope therapy, and requirement for invasive mechanical ventilation were independent risk factors for ACM. CONCLUSIONS: In this national registry, the PE profile was found to be a high-acuity clinical presentation with distinctive treatment patterns and a poor short-term prognosis. Advances in the management of PE may necessitate both the development of novel targeted therapies as well as systems-based strategies to identify high-risk patients early in their course.

Patterns of intensive care unit admissions in patients hospitalized for heart failure: insights from the RO-AHFS registry.

AIM: The present study aims to describe the epidemiology, baseline clinical characteristics, in-hospital management, and outcome of patients hospitalized for heart failure admitted directly or transferred to the ICU. METHODS AND RESULTS: The Romanian Acute Heart Failure Syndromes (RO-AHFS) registry prospectively enrolled 3224 consecutive patients between January 2008 and May 2009 admitted with a primary diagnosis of heart failure. Participants were classified by ICU admission status (i.e. ICU+/ICU-). Independent clinical predictors of ICU admission and in-hospital mortality were identified using multivariable logistic regression analysis. Overall, 10.7% of patients required ICU level care, 32% as a direct ICU admission, with 68% as an ICU transfer during hospitalization. Patients admitted to the ICU had a mean age of 68.1 ± 11.3 years, 61% were men, 67% had an ischemic cause, and 44% presented with de-novo heart failure. ICU+ patients more frequently presented with low SBP and pulse pressure and abnormal renal function. Mechanical ventilation was required in 32.7% and intravenous inotropes were administered to 56.7% of ICU+ patients. ICU+ patients had higher in-hospital mortality compared to ICU- patients (17.3 vs. 6.5%). Patients admitted directly to the ICU had a 15.3% mortality rate compared to 18.4% in those transferred after admission. Age, serum sodium, SBP below 110 mmHg, and left-ventricular ejection fraction less than 45% were predictive of ICU admission, whereas for ICU+ patients, age, vasopressor, and mechanical ventilation utilization were predictive of mortality. CONCLUSIONS: Patients admitted directly or transferred to the ICU are at a high risk of in-hospital mortality. Clinical variables commonly measured at the time of admission may facilitate disposition decision-making including early triage to the ICU.

Inadequate heart rate control despite widespread use of beta-blockers in outpatients with stable CAD: findings from the international prospective CLARIFY registry.

BACKGROUND: To use CLARIFY, a prospective registry of patients with stable CAD (45 countries), to explore heart rate (HR) control and beta-blocker use. METHODS: We analyzed the CLARIFY population according to beta-blocker use via descriptive statistics with Pearson's χ(2) test for comparisons, as well as a multivariable stepwise model. RESULTS: Data on beta-blocker use was available for 32,914 patients, in whom HR was 68 ± 11 bpm; patients with angina, previous myocardial infarction, and heart failure had HRs of 69 ± 12, 68 ± 11, and 70 ± 12 bpm, respectively. 75% of these patients were receiving beta-blockers. Bisoprolol (34%), metoprolol tartrate (16%) or succinate (13%), atenolol (15%), and carvedilol (12%) were mostly used; mean dosages were 49%, 76%, 35%, 53%, and 45% of maximum doses, respectively. Patients aged <65 years were more likely to receive beta-blockers than patients ≥ 75 years (P<0.0001). Gender had no effect. Subjects with HR ≤ 60 bpm were more likely to be on beta-blockers than patients with HR ≥ 70 bpm (P<0.0001). Patients with angina, previous myocardial infarction, heart failure, and hypertension were more frequently receiving beta-blockers (all P<0.0001), and those with PAD and asthma/COPD less frequently (both P<0.0001). Beta-blocker use varied according to geographical region (from 87% to 67%). CONCLUSIONS: Three-quarters of patients with stable CAD receive beta-blockers. Even so, HR is insufficiently controlled in many patients, despite recent guidelines for the management of CAD. There is still much room for improvement in HR control in the management of stable CAD.

Assessment of dyspnea early in acute heart failure: patient characteristics and response differences between likert and visual analog scales.

BACKGROUND: Dyspnea is the most common symptom in acute heart failure (AHF), yet how to best measure it has not been well defined. Prior studies demonstrate differences in dyspnea improvement across various measurement scales, yet these studies typically enroll patients well after the emergency department (ED) phase of management. OBJECTIVES: The aim of this study was to determine predictors of early dyspnea improvement for three different, commonly used dyspnea scales (i.e., five-point absolute Likert scale, 10-cm visual analog scale [VAS], or seven-point relative Likert scale). METHODS: This was a post hoc analysis of URGENT Dyspnea, an observational study of 776 patients in 17 countries enrolled within 1 hour of first physician encounter. Inclusion criteria were broad to reflect real-world clinical practice. Prior literature informed the a priori definition of clinically significant dyspnea improvement. Resampling-based multivariable models were created to determine patient characteristics significantly associated with dyspnea improvement. RESULTS: Of the 524 AHF patients, approximately 40% of patients did not report substantial dyspnea improvement within the first 6 hours. Baseline characteristics were similar between those who did or did not improve, although there were differences in history of heart failure, coronary artery disease, and initial systolic blood pressure. For those who did improve, patient characteristics differed across all three scales, with the exception of baseline dyspnea severity for the VAS and five-point Likert scale (c-index ranged from 0.708 to 0.831 for each scale). CONCLUSIONS: Predictors of early dyspnea improvement differ from scale to scale, with the exception of baseline dyspnea. Attempts to use one scale to capture the entirety of the dyspnea symptom may be insufficient.

Hypertension prevalence and control in Romania at a seven-year interval. Comparison of SEPHAR I and II surveys.

OBJECTIVES: To present the current epidemiologic situation regarding hypertension's prevalence and control in Romania's adult population (revealed by SEPHAR II survey results) and to evaluate their tendency during the last 7 years (by comparing with the SEPHAR I survey results). METHODS: The two SEPHAR cross-sectional national surveys were conducted on a representative sample for the Romanian adult population (SEPHAR I: 2017 individuals aged 18-85 years, 45% response rate, SEPHAR II: 1975 individuals aged 18-80 years, 69% response rate), by means of questionnaire interview, blood pressure (BP) and anthropometric measurements during two study visits. Hypertension was defined as SBP at least 140  mmHg and/or DBP at least 90  mmHg at both study visits or previously diagnosed hypertension under current treatment. Controlled BP was defined as SBP less than 140  mmHg and DBP less than 90  mmHg in currently treated hypertensive individuals. RESULTS: Prevalence of hypertension in Romanian is 40.41%, awareness of hypertension is 69.55%, with 59.15% hypertensive individuals under current treatment with a control rate of 25%. In the last 7 years, there has been a 10.7% decrease in hypertension's prevalence together with an increase by 57% in awareness of hypertension and an increase by 52% in treatment of hypertension, leading to almost doubling of the hypertension's control rate in all hypertensive individuals. CONCLUSION: Although in the last 7 years, the tendency of hypertension's prevalence seems to be a descending one with an increasing trend in awareness, treatment and control of this condition, hypertension in Romania at this time still remains an 'unsolved equation'.

The predictive value of transaminases at admission in patients hospitalized for heart failure: findings from the RO-AHFS registry.

BACKGROUND: Transaminases are commonly elevated in both the inpatient and ambulatory settings in heart failure (HF). AIMS: To determine the prevalence and degree of elevated transaminase levels at admission and to evaluate the association between transaminase levels and in-hospital morbidity and mortality. METHODS: Over a 12-month period, the Romanian Acute Heart Failure Syndromes (RO-AHFS) registry enrolled consecutive patients hospitalized for HF at 13 medical centres. A post-hoc analysis of the 489 patients (15.2%) with alanine transaminase (ALT) and aspartate transaminase (AST) (upper limits of normal 31 IU/l and 32 IU/l, respectively) measured at baseline was performed. In-hospital mortality was compared across quartiles using multivariable Cox regression models. RESULTS: The prevalences of elevated ALT and AST were 28% and 24% and the medians (interquartile range) were 22 (16-47) and 23 (16-37 IU/L). Patients with elevated transaminases more commonly had right HF, cardiogenic shock, or an ejection fraction <45%. Patients with an ALT in the highest quartile were more likely to present with hypotension and a low pulse pressure, to have electrocardiographic evidence of left ventricular dyssynchrony and echocardiographic findings including increased left ventricular dimensions, reduced left ventricular ejection fraction, and valvular heart disease, to require inotropic or vasopressor support during hospitalization, and to report lower ß-blocker and angiotensin-converting enzyme inhibitor utilization. After adjusting for potential confounders, ALT was directly associated with BUN increases ≥10 mg/dl, necessity for intensive care unit admission, and longer length of stay. Patients in the highest quartile of ALT experienced significantly higher rates of all-cause mortality. CONCLUSIONS: In patients hospitalized for HF, there is a graded relationship between admission transaminase levels and surrogates for in-hospital morbidity, while more pronounced elevations of ALT predict in-hospital mortality independent of known prognostic indicators.

Haemodynamic effects, safety, and pharmacokinetics of human stresscopin in heart failure with reduced ejection fraction.

AIMS: Human stresscopin is a corticotropin-releasing factor (CRF) type 2 receptor (CRFR2) selective agonist and a member of the CRF peptide family. Stimulation of CRFR2 improves cardiac output and left ventricular ejection fraction (LVEF) in patients with stable heart failure (HF) with reduced LVEF. We examined the safety, pharmacokinetics, and effects on haemodynamics and serum biomarkers of intravenous human stresscopin acetate (JNJ-39588146) in patients with stable HF with LVEF ≤ 35% and cardiac index (CI) ≤ 2.5 L/min/m(2). METHODS AND RESULTS: Sixty-two patients with HF and LVEF ≤ 35% were instrumented with a pulmonary artery catheter and randomly assigned (ratio 3:1) to receive an intravenous infusion of JNJ-39588146 or placebo. The main study was an ascending dose study of three doses (5, 15, and 30 ng/kg/min) of study drug or placebo administered in sequential 1 h intervals (3 h total). Statistically significant increases in CI and reduction in systemic vascular resistance (SVR) were observed with both the 15 ng/kg/min (2 h time point) and 30 ng/kg/min (3 h time point) doses of JNJ-39588146 without significant changes in heart rate (HR) or systolic blood pressure (SBP). No statistically significant reductions in pulmonary capillary wedge pressure (PCWP) were seen with any dose tested in the primary analysis, although a trend towards reduction was seen. CONCLUSION: In HF patients with reduced LVEF and CI, ascending doses of JNJ-39588146 were associated with progressive increases in CI and reductions in SVR without significant effects on PCWP, HR, or SBP. TRIAL REGISTRATION: NCT01120210.

The Romanian Acute Heart Failure Syndromes (RO-AHFS) registry.

AIMS: The objective of the RO-AHFS registry was to evaluate the epidemiology, clinical presentation, inpatient management, and hospital course in a population hospitalized for acute heart failure syndromes. METHODS: During a 12-month period, 13 Romanian medical centers enrolled all consecutive patients hospitalized with a primary diagnosis of AHFS. Patients were classified into the following 5 clinical profiles at admission: acute decompensated heart failure, cardiogenic shock, pulmonary edema, right heart failure, and hypertensive heart failure. Statistical significance was assessed using Fisher exact test or the χ(2) test for categorical variables and a 1-way analysis of variance for continuous variables. Independent predictors of in-hospital all-cause mortality (ACM) were identified using a multivariate logistic regression model. RESULTS: A total of 3,224 consecutive patients hospitalized with AHFS were enrolled. The cohort had a mean age of 69.2 ± 11.8 years and 56% were men. The mean left ventricular ejection fraction was 37.7% ± 12.5%. The percentage of patients treated with evidence-based heart failure therapies increased from admission to discharge, but even at discharge, only 56%, 66%, and 54% of patients were on a ß-blocker, an angiotensin-converting enzyme inhibitors or an angiotensin receptor blocker, and a mineralocorticoid receptor antagonist, respectively. In-hospital ACM was 7.7% with substantial variation between sites (4.1%-11.0%). Increasing age, inotrope therapy, the presence of life-threatening ventricular arrhythmias, and elevated baseline blood urea nitrogen were all found to be independent risk factors for in-hospital ACM, whereas elevated systolic blood pressure and baseline treatment with a ß-blocker had a protective effect. CONCLUSIONS: The RO-AHFS study found substantial variation both among sites and between Romania and other European countries. National and regional registries have important clinical implications for patient care and the design and conduct of global clinical trials.

Effects of istaroxime on diastolic stiffness in acute heart failure syndromes: results from the Hemodynamic, Echocardiographic, and Neurohormonal Effects of Istaroxime, a Novel Intravenous Inotropic and Lusitropic Agent: a Randomized Controlled Trial in Patients Hospitalized with Heart Failure (HORIZON-HF) trial.

BACKGROUND: Istaroxime is a novel intravenous agent with inotropic and lusitropic properties related to inhibition of the Na+/K+ adenosine triphosphatase and stimulation of sarcoplasmic reticulum calcium adenosine triphosphatase activity. We analyzed data from HORIZON-HF, a randomized, controlled trial evaluating the short-term effects of istaroxime in patients hospitalized with heart failure and left ventricular ejection fraction < or = 35% to test the hypothesis that istaroxime improves diastolic stiffness in acute heart failure syndrome. METHODS: One hundred twenty patients were randomized 3:1 (istaroxime/placebo) to a continuous 6-hour infusion of 1 of 3 doses of istaroxime or placebo. All patients underwent pulmonary artery catheterization and comprehensive 2-dimensional/Doppler and tissue Doppler echocardiography at baseline and at the end of the 6-hour infusion. We quantified diastolic stiffness using pressure-volume analysis and tissue Doppler imaging of the lateral mitral annulus (E'). RESULTS: Baseline characteristics were similar among all groups, with mean age 55 +/- 11 years, 88% men, left ventricular ejection fraction 27% +/- 7%, systolic blood pressure (SBP) 116 +/- 13 mm Hg, and pulmonary capillary wedge pressure (PCWP) 25 +/- 5 mm Hg. Istaroxime administration resulted in an increase in E' velocities, whereas there was a decrease in E' in the placebo group (P = .048 between groups). On pressure-volume analysis, istaroxime decreased end-diastolic elastance (P = .0001). On multivariate analysis, increasing doses of istaroxime increased E' velocity (P = .043) and E-wave deceleration time (P = .001), and decreased E/E' ratio (P = .047), after controlling for age, sex, baseline ejection fraction, change in PCWP, and change in SBP. CONCLUSIONS: Istaroxime decreases PCWP, increases SBP, and decreases diastolic stiffness in patients with acute heart failure syndrome.

Acute hemodynamic effects of tolvaptan, a vasopressin V2 receptor blocker, in patients with symptomatic heart failure and systolic dysfunction: an international, multicenter, randomized, placebo-controlled trial.

OBJECTIVES: This study sought to assess the acute hemodynamic effect of vasopressin V(2) receptor antagonism. BACKGROUND: In decompensated heart failure (HF), tolvaptan, a vasopressin V(2) receptor antagonist, has been shown to improve congestion. It has not yet been established whether these improvements may be associated with the hemodynamic effects of tolvaptan. METHODS: A total of 181 patients with advanced HF on standard therapy were randomized to double-blind treatment with tolvaptan at a single oral dose (15, 30, or 60 mg) or placebo. RESULTS: Tolvaptan at all doses significantly reduced pulmonary capillary wedge pressure (-6.4 +/- 4.1 mm Hg, -5.7 +/- 4.6 mm Hg, -5.7 +/- 4.3 mm Hg, and -4.2 +/- 4.6 mm Hg for the 15-mg, 30-mg, 60-mg, and placebo groups, respectively; p < 0.05 for all tolvaptan vs. placebo). Tolvaptan also reduced right atrial pressure (-4.4 +/- 6.9 mm Hg [p < 0.05], -4.3 +/- 4.0 mm Hg [p < 0.05], -3.5 +/- 3.6 mm Hg, and -3.0 +/- 3.0 mm Hg for the 15-mg, 30-mg, 60-mg, and placebo groups, respectively) and pulmonary artery pressure (-5.6 +/- 4.2 mm Hg, -5.5 +/- 4.1 mm Hg, -5.2 +/- 6.1 mm Hg, and -3.0 +/- 4.7 mm Hg for the 15-mg, 30-mg, 60-mg, and placebo groups, respectively; p < 0.05). Tolvaptan increased urine output by 3 h in a dose-dependent manner (p < 0.0001), without changes in renal function. CONCLUSIONS: In patients with advanced HF, tolvaptan resulted in favorable but modest changes in filling pressures associated with a significant increase in urine output. These data provide mechanistic support for the symptomatic improvements noted with tolvaptan in patients with decompensated HF. (Heart Pressure Assessment Study With Tolvaptan to Treat Congestive Heart Failure; NCT00132886).

Design and rationale of the URGENT Dyspnea study: an international, multicenter, prospective study.

BACKGROUND: Dyspnea is a key target in both clinical management and clinical trials of acute heart failure syndromes and its relief important to patients, clinicians, investigators, and regulatory approval agencies. Despite its importance, the impact of early therapy on dyspnea is not well known. The severity of dyspnea may also be influenced by the conditions under which it is measured (ie, sitting up or lying down). URGENT Dyspnea (Ularitide Global Evaluation in Acute Decompensated Heart Failure) is a prospective multicenter study designed to address these issues. METHODS AND RESULTS: Consenting adult patients with dyspnea secondary to acute heart failure syndromes are eligible. Patients must be interviewed within one hour of first physician evaluation, typically in an emergency department or acute care setting, with dyspnea assessed by the patient using both a 5-point Likert scale and 10-point visual analog scale in the sitting (60 degrees) and then supine (20 degrees ) position if symptomatically able. Improvement of dyspnea by change in Likert and visual analog scale scores at 6 h is the primary endpoint. CONCLUSIONS: Timing of dyspnea measurement and the conditions under which it is measured may influence dyspnea severity and this may have significant implications for future acute heart failure syndromes clinical trial design that target dyspnea.

Hemodynamic, echocardiographic, and neurohormonal effects of istaroxime, a novel intravenous inotropic and lusitropic agent: a randomized controlled trial in patients hospitalized with heart failure.

OBJECTIVES: We examined the hemodynamic, echocardiographic, and neurohormonal effects of intravenous istaroxime in patients hospitalized with heart failure (HF). BACKGROUND: Istaroxime is a novel intravenous agent with inotropic and lusitropic properties related to inhibition of Na/K adenosine triphosphatase (ATPase) and stimulation of sarcoplasmic reticulum calcium ATPase. METHODS: One hundred twenty patients admitted with HF and reduced systolic function were instrumented with a pulmonary artery catheter within 48 h of admission. Three sequential cohorts of 40 patients each were randomized 3:1 istaroxime:placebo to a continuous 6-h infusion. The first cohort received 0.5 microg/kg/min, the second 1.0 microg/kg/min, and the third 1.5 microg/kg/min istaroxime or placebo. RESULTS: All doses of istaroxime lowered pulmonary capillary wedge pressure (PCWP), the primary end point (mean +/- SD: -3.2 +/- 6.8 mm Hg, -3.3 +/- 5.5 mm Hg, and -4.7 +/- 5.9 mm Hg compared with 0.0 +/- 3.6 mm Hg with placebo; p < 0.05 for all doses). Istaroxime significantly decreased heart rate (HR) and increased systolic blood pressure (SBP). Cardiac index increased and left ventricular end-diastolic volume decreased significantly only with 1.5 microg/kg/min. On echocardiography, left ventricular end diastolic volume and deceleration time improved with 1.5 microg/kg/min. There were no changes in neurohormones, renal function, or troponin I. Adverse events were not life threatening and were dose related. CONCLUSIONS: In patients hospitalized with HF, istaroxime improved PCWP and possibly diastolic function. In contrast to available inotropes, istaroxime increased SBP and decreased HR. (A Phase II Trial to Assess Hemodynamic Effects of Istaroxime in Pts With Worsening HF and Reduced LV Systolic Function [HORIZON-HF]; NCT00616161).

Rationale and design of the hemodynamic, echocardiographic and neurohormonal effects of istaroxime, a novel intravenous inotropic and lusitropic agent: a randomized controlled trial in patients hospitalized with heart failure (HORIZON-HF) trial.

BACKGROUND: Current inotropes have inodilator properties and, although are frequently used in acute heart failure syndromes, do not improve outcomes, likely from reduction in systolic blood pressure and increasing in arrhythmias, causing worsened myocardial ischemia and end-organ damage. Istaroxime is a novel agent that, in animal models, has both inotropic (inhibition of the Na/K ATPase channel) and lusitropic (stimulation of sarcoplasmic reticulum calcium ATPase activity) effects. HORIZON-HF is designed to test the hypothesis that istaroxime is effective in improving central hemodynamics and left ventricular (LV) function, without lowering systolic blood pressure, increasing heart rate, and worsening renal function or myocardial necrosis. METHODS AND RESULTS: This was a phase 2, randomized, double-blind, placebo-controlled, multicenter dose escalation exploratory study comparing 3 different doses of istaroxime to placebo in patients with LV systolic dysfunction (LV ejection fraction

Awareness and perception of heart failure among European cardiologists, internists, geriatricians, and primary care physicians.

AIMS: To assess awareness of heart failure (HF) management recommendations in Europe among cardiologists (C), internists and geriatricians (I/G), and primary care physicians (PCPs). METHODS AND RESULTS: The Study group on HF Awareness and Perception in Europe (SHAPE) surveyed randomly selected C (2041), I/G (1881), and PCP (2965) in France, Germany, Italy, the Netherlands, Poland, Romania, Spain, Sweden, and the UK. Each physician completed a 32-item questionnaire about the diagnosis and treatment of HF (left ventricular ejection fraction <40%). This report provides an analysis of HF awareness among C, I/G, and PCP. Seventy-one per cent I/G and 92% C use echocardiography, and 43% I/G and 82% C use echo-Doppler as a routine diagnostic test (both P < 0.0001). In contrast, 75% PCP use signs and symptoms to diagnose HF. Fewer I/G would use an angiotensin-converting enzyme (ACE)-inhibitor in >90% of their patients (64 vs. 82% C, P < 0.0001), whereas only 47% PCP would routinely prescribe an ACE-inhibitor. Worsening HF was considered a risk of ACE-inhibitor therapy by 35% PCP. I/G and PCP consistently do not prescribe target ACE-inhibitor doses (P < 0.0001 vs. C). Only 39% I/G would use a beta-blocker in >50% of their patients (vs. 73% C, P < 0.0001). Also, only 5% PCP would always, and 35% often, prescribe a beta-blocker and reach target doses in only 7-29%. Moreover, 34% PCP and 26% I/G vs. 11% C (P < 0.0001) do not start a beta-blocker in patients with mild HF, who are already on an ACE-inhibitor and are on diuretic. In mild, stable HF, 39% PCP and 18% I/G would only prescribe diuretics, vs. 7% C (P < 0.0001). In patients with worsening HF in sinus rhythm and on an optimal ACE-inhibitor, beta-blockade and diuretics, significantly more C would add spironolactone, but I/G would more often add digoxin. CONCLUSION: Although each physician group lacks complete adherence to guideline-recommended management strategies, these are used significantly less well by I, G, and PCPs, indicating the need for education of these essential healthcare providers.

Public awareness of heart failure in Europe: first results from SHAPE.

AIMS: Appropriate heart failure (HF) care and adequate resourcing require recognition of its clinical, social, and economic importance by the general public besides healthcare authorities and providers. The extent of public awareness in Europe is not known. METHODS AND RESULTS: A total of 7958 subjects were randomly selected from nine European countries (minimum 100/group per country). Each completed a 32-question survey on HF covering recognition, impact on health, comparative prevalence and severity, treatment, and costs. Although 86% of respondents had heard of HF, only 3% could correctly identify HF from a description of typical symptoms and signs, 31% correctly identified angina, and 51% identified transient ischaemic attack/stroke. Only 29% thought that HF signs and symptoms indicate a 'severe' condition. Most thought that HF patients should reduce all physical activity and 34% believed HF a normal consequence of ageing. Sixty-seven per cent thought that HF patients live longer than cancer patients. Only 9% believed that HF leads to greater healthcare expenditure than cancer, HIV, or diabetes. Overall, responses were comparable between countries. CONCLUSION: In Europe, community awareness of HF is low. Therefore, the general public is unlikely to demand appropriate measures by healthcare authorities and providers. A better understanding of HF could improve its prevention and management. Strategies to educate the public about HF are needed.

Echocardiographic predictors of embolic events in infective endocarditis.

BACKGROUND: Systemic embolisation occurs in 22% to 50% of patients with infective endocarditis (IE). Up to 65% of embolic events (EE) involve the central nervous system which increases the mortality rate. Several echocardiographic studies have demonstrated higher embolic rates with the increase of vegetation (VEG) dimensions and mobility. AIM: To define echocardiographic parameters which can help in identifying patients with a high risk of EE and to assess the value of transesophageal echocardiography (TEE) in predicting EE in patients with IE. METHODS: 236 patients (58% male, mean age 47.8+/-6) diagnosed with IE according to Duke criteria were followed for 3 years or until cardiac surgery. Echocardiographic parameters measured on VEG included the maximum length, thickness, the narrowest diameter, neck and mobility. RESULTS: The rate of EE was 51.27% without any significant differences with respect to gender, age, fever, anaemia, VEG site or the presence of a significant regurgitation murmur. The univariate analysis showed a significant correlation between EE and IE caused by staphylococcus, IE of the right heart, and the length as well as mobility of VEG. The only independent predictors of EE were the maximum VEG length >15 mm and the increased mobility of VEG with a maximal displacement angle >60.7 degrees. In 23% of patients EE occurred after the initiation of antibiotic treatment. VEG in this group were big and very mobile (length >15 mm, maximal angle of displacement >65 degrees). CONCLUSIONS: 1. Vegetation dimension and mobility determined by TEE are important predictors of the embolic risk. 2. Significant echocardiographic predictors of embolic events included vegetation length >15 mm, neck/thickness ratio >0.69, and maximal angle of displacement of vegetation during cardiac cycle >60.7 degrees. 3. During antibiotic treatment, the embolic risk depends only on vegetation mobility and dimension.

Increasing awareness and perception of heart failure in Europe and improving care--rationale and design of the SHAPE Study.

UNLABELLED: In the last decennia heart failure has become one of the most important diseases worldwide in terms of prevalence, morbidity, life expectancy, and in health care management and costs. Despite significant improvements in prevention and treatment, heart failure remains a frequently occurring disorder with increasing incidence and a high hospitalisation and death rate. As major health care problem it deserves full attention of health care authorities. Unfortunately, the seriousness of heart failure and the therapeutic possibilities are often not recognised by those directly involved, i.e. the doctor, the patient or his relatives, let alone that they are known to the general public and health care authorities. The SHAPE study aims at improving heart failure care by increasing awareness and perception of the disease in Europe. Firstly, awareness and perception of heart failure will be documented in the general public, primary care physicians and specialists (cardiologists, internists and geriatricians) in 9 European countries: France, Germany, Italy, the Netherlands, Poland, Romania, Spain, Sweden and the UK. Subsequently, the results will be used to design and carry out suitable awareness and educational programmes in these groups, aimed at improving heart failure care and research. Finally, the results of these programmes will be tested in a second documentation phase and adaptations made where needed. This manuscript describes the rationale and design of the first phase, the Documentation Phase.During the first documentation phase, 800 participants per country selected based on sex, two age groups and urban vs. rural location (100/cell) will be surveyed using a 32-question interview. Questions for the general public focus on recognition, incidence and prevalence, severity and prognosis of the disease in comparison to other disease areas, like cancer, on quality of life, therapeutic possibilities and availability of care. The primary care physician (PCP) survey aims at receiving a minimum of 300 responses. A questionnaire with 33 closed questions will be used covering the PCP's knowledge of heart failure, including prevalence, aetiology, new diagnostic and therapeutic developments and health care costs. Questions concerning diagnostic procedures and various treatments carried out by the PCP in his own practice, as well as referral patterns for diagnostic procedures and for specialist care. Questions relating to the type of practice and number of patients in each PCP's clinical practice. A minimum of 150 cardiologists and 150 internists + geriatricians will be surveyed per country. The specialist's questionnaire contains 31 questions focusing on identification of heart failure patients, patients at risk, use and availability of diagnostic tools, importance of therapies and order of treatment, perceived risks of treatment, relevance of counselling and advice, use of paramedical personnel, and questions concerning practice size, type of practice and number of patients with heart failure. CONCLUSION: This first part of the SHAPE study will provide important information about the level of knowledge and understanding of heart failure of the general public, as well as the perception of the relevance of heart failure and appropriate diagnostic and therapeutic approaches by both the primary care physician and the medical specialist. This knowledge will be extremely valuable when it comes to defining optimal educational programmes in the different target groups studied in SHAPE necessary to implement appropriate heart failure care in Europe and to obtain the means to do so.