Cezar Macarie

Prof. Dr. C.C. Iliescu Institute for Emergency Cardiovascular Diseases, Bucureşti, Bucureşti, Romania

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Publications (29)121.49 Total impact

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    ABSTRACT: 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 +/- 27.1 mg) of IV furosemide for a shorter duration (i.e. 69.3 +/- 22.3 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.
    Journal of Cardiovascular Medicine 09/2014; DOI:10.2459/JCM.0000000000000192 · 1.41 Impact Factor
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    ABSTRACT: 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 chi(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.
    International Journal of Cardiology 07/2014; 176(1). DOI:10.1016/j.ijcard.2014.06.052 · 6.18 Impact Factor
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    ABSTRACT: 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.ResultsOf 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.ResumenAntecedentesLa disnea es el síntoma más frecuente en la insuficiencia cardiaca aguda (ICA), sin embargo no ha sido bien definida la mejor manera de medirla. Estudios previos demuestran diferencias en la mejoría de la disnea a través de varias escalas de medida, sin embargo estos estudios suelen reclutar pacientes bastante después de la fase de manejo en el SU.ObjetivosEl objetivo de este estudio fue determinar los predictores precoces de mejoría de la disnea para tres escalas de disnea diferentes frecuentemente utilizadas (escala Likert absoluta de 5 puntos, escala visual analógica [EVA] de 10 cm o escala Likert relativa de 7 puntos).MétodosSe trata de un análisis post hoc del estudio observacional Disnea URGENTE, que reclutó 776 pacientes dentro de la primera hora tras la primera valoración médica en 17 países. Los criterios de inclusión fueron amplios para reflejar la práctica clínica en el mundo real. La literatura previa documentó la definición a priori de la mejoría significativa de disnea. Se crearon modelos multivariables basados en el remuestreo para determinar las características de los pacientes significativamente asociadas con la mejoría de la disnea.ResultadosDe los 524 pacientes con ICA, aproximadamente un 40% de los pacientes no documentaron una mejoría sustancial de la disnea en las 6 primeras horas. Las características basales fueron similares entre los que mejoraron y los que no, aunque hubo diferencias en la historia de insuficiencia cardiaca, enfermedad coronaria y presión arterial sistólica inicial. Para aquéllos que mejoraron, las características del paciente difirieron en las tres escalas, con la excepción de la gravedad de la disnea basal para la EVA y en la escala Likert de 5 puntos (el índice-c varió desde 0,708 hasta 0,831 para cada escala).ConclusionesLos predictores de la mejoría precoz de disnea difieren dependiendo de la escala, con la excepción de la disnea basal. Los intentos para utilizar una sola escala para categorizar la totalidad del síntoma disnea pueden ser insuficientes.
    Academic Emergency Medicine 06/2014; 21(6). DOI:10.1111/acem.12390 · 2.20 Impact Factor
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    ABSTRACT: 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. 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. 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.
    Journal of Cardiovascular Medicine 04/2014; 16(5). DOI:10.2459/JCM.0000000000000030 · 1.41 Impact Factor
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    ABSTRACT: 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). 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. 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. 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'.
    Journal of Hypertension 10/2013; 32(1). DOI:10.1097/01.hjh.0000434937.62412.24 · 4.22 Impact Factor
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    ABSTRACT: Background: Transaminases are commonly elevated in both the inpatient and ambulatory settings in heart failure (HF).
    06/2013; 2(2):99-108. DOI:10.1177/2048872612474906
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    ABSTRACT: AimsHuman 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-9588146) in patients with stable HF with LVEF ≤35% and cardiac index (CI) ≤2.5 L/min/m2.Methods and resultsSixty-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-9588146 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-9588146 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-9588146 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; 15(6). DOI:10.1093/eurjhf/hft023 · 6.58 Impact Factor
  • Journal of Cardiac Failure 08/2012; 18(8):S69-S70. DOI:10.1016/j.cardfail.2012.06.461 · 3.07 Impact Factor
  • Journal of Cardiac Failure 08/2012; 18(8):S75-S76. DOI:10.1016/j.cardfail.2012.06.481 · 3.07 Impact Factor
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    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. DOI:10.1016/j.ahj.2011.03.033 · 4.56 Impact Factor
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    ABSTRACT: Objective Assessment of obese patients with heart failure by left ventricular systolic dysfunction (LVEF<40%). Methods 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. Results 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. Conclusions 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. DOI:10.1016/S1878-6480(10)70098-7
  • Journal of Cardiac Failure 08/2009; 15(6). DOI:10.1016/j.cardfail.2009.06.313 · 3.07 Impact Factor
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    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. DOI:10.1016/j.ahj.2009.03.007 · 4.56 Impact Factor
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    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. DOI:10.1016/j.jacc.2008.08.013 · 15.34 Impact Factor
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    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. DOI:10.1093/eurheartj/ehn196 · 14.72 Impact Factor
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    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. DOI:10.1016/j.jacc.2008.03.015 · 15.34 Impact Factor
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    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. DOI:10.1097/MJT.0b013e31816b436e · 1.13 Impact Factor
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    ABSTRACT: 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. 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 <or= 35%) admitted to the hospital with worsening HF. Three cohorts of 40 patients each were randomized after an initial stabilization period of <48 h 3:1 to istaroxime 0.5, 1.0, or 1.5 microg/kg/min versus placebo infused over 6 h, with increasing doses after each cohort. The primary endpoint was change in pulmonary capillary wedge pressure from baseline, whereas secondary endpoints were improvement in other hemodynamic parameters, changes in echocardiographic assessment of LV systolic and diastolic function, neurohonal activation, renal function, and myocardial integrity. Pharmacokinetics and safety were also recorded. The novel inotropic and lusitropic agent, istaroxime, was tested in acute heart failure syndromes using a comprehensive assessment of cardiovascular function in addition to hemodynamic measurements.
    American journal of therapeutics 01/2008; 15(3):231-40. DOI:10.1097/MJT.0b013e31816d9186 · 1.13 Impact Factor
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    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. DOI:10.1093/eurheartj/ehi447 · 14.72 Impact Factor
  • European Journal of Heart Failure Supplements 06/2004; 3(S1).

Publication Stats

330 Citations
121.49 Total Impact Points

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Institutions

  • 2008–2014
    • Prof. Dr. C.C. Iliescu Institute for Emergency Cardiovascular Diseases
      Bucureşti, Bucureşti, Romania
    • Northwestern University
      • Feinberg School of Medicine
      Evanston, IL, United States
  • 2013
    • Carol Davila University of Medicine and Pharmacy
      Bucureşti, Bucureşti, Romania
  • 2004–2011
    • Institute for Cardiovascular Diseases
      Socola, Iaşi, Romania
    • Universitatea de Medicina si Farmacie Craiova
      Croiova, Dolj, Romania