[show abstract][hide abstract] ABSTRACT: 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/m2. 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.
European Journal of Heart Failure 03/2013; · 5.25 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
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.
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 β-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 β-blocker had a protective effect.
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.
American heart journal 07/2011; 162(1):142-53.e1. · 4.65 Impact Factor
[show abstract][hide abstract] ABSTRACT: Objective
Assessment of obese patients with heart failure by left ventricular systolic dysfunction (LVEF<40%).
We included in our study 293 patients with heart failure by left ventricular systolic dysfunction. We analyzed clinical factors (heart failure etiology, functional class, risk factors – hypertension,dyslipidemia, smoking,diabetes mellitus,BMI),electrocardiographic factors (LVH presence,conduction and rhythm disturbances),echocardiographic features (LVEF,diastolic function, LVH, systolic PAP) and laboratory data (Hb,serum creatinine,uric acid,WBC count,serum BNP). Obesity was defined as presence of a BMI>30 kg/m2.
Of the 293 patients included there were 89 obese patients (30.9%)-73 males (82%) and 16 females(18%).Heart failure was ischemic at 163 patients (55.6%). At obese patients we observed a more frequent association with hypertension(78.6% of obese patients versus 55.4% nonobese patients;p=0.001); dyslipidemia (70.8% of obese patients versus 42.6%;p=0001); diabetes mellitus (43.8% vs. 14.7%;p=0,0001). Heart failure was more frequent of ischemic etiology at obese patients (66.3% vs. 50.9%; p=0.015). Likewise, EF was greater at obese patients (32.22 ±6.07% vs. 30.06±6.85%;p=0.011) and sinus rhythm was more frequent, too(78.6% vs. 67.15%; p = 0,047). There were no significant differences between BNP at obese and nonobese patients (860.04±803,97 pg/ml vs. 931.58±881,28 pg/ml;p=0,51,ns),neither between diastolic function,presence of LVH,QRS duration, enal dysfunction and other factors studied.
A significant proportion of patients with heart failure by left ventricular systolic dysfunction are obese. At obese patients with heart failure by left ventricular systolic dysfunction there is a more frequent association with other risk factors (hypertension, dyslipidemia, diabetes mellitus) and ischemic etiology of heart failure. BNP values were not significantly different at obese patients with systolic heart failure versus nonobese patients.
Archives of Cardiovascular Diseases Supplements 01/2010; 2(1):32-32.
[show abstract][hide abstract] ABSTRACT: 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.
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').
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.
Istaroxime decreases PCWP, increases SBP, and decreases diastolic stiffness in patients with acute heart failure syndrome.
American heart journal 06/2009; 157(6):1035-41. · 4.65 Impact Factor
[show abstract][hide abstract] ABSTRACT: This study sought to assess the acute hemodynamic effect of vasopressin V(2) receptor antagonism.
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.
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.
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.
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).
Journal of the American College of Cardiology 12/2008; 52(19):1540-5. · 14.09 Impact Factor
[show abstract][hide abstract] ABSTRACT: We examined the hemodynamic, echocardiographic, and neurohormonal effects of intravenous istaroxime in patients hospitalized with heart failure (HF).
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.
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.
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.
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).
Journal of the American College of Cardiology 07/2008; 51(23):2276-85. · 14.09 Impact Factor
[show abstract][hide abstract] ABSTRACT: To assess awareness of heart failure (HF) management recommendations in Europe among cardiologists (C), internists and geriatricians (I/G), and primary care physicians (PCPs).
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.
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.
European Heart Journal 07/2008; 29(14):1739-52. · 14.10 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
American journal of therapeutics 06/2008; 15(4):299-303. · 1.29 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
European Heart Journal 12/2005; 26(22):2413-21. · 14.10 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
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).
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.
Kardiologia polska 06/2004; 60(6):535-40. · 0.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
Cardiovascular Drugs and Therapy 04/2004; 18(2):153-9. · 2.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: We have chosen this case of sporadic atrial myxoma for our presentation because it had a particular evolution, with recurrence at 8 years after surgical excision (echocardiography was performed every year) and a particular diagnostic means - at echocardiographic follow-up, the patient being asymptomatic. This presentation, together with a review of literature included in the article, emphasizes the importance of a careful postoperative follow-up of the patients and the existence of some particular aspects of the evolution and symptomatology of recurrent atrial myxoma.
Romanian journal of internal medicine = Revue roumaine de médecine interne 02/2004; 42(3):625-34.