Biomedical subjects

Viorel G Florea

Publications and source records attributed to Viorel G Florea.

8 recordsLinked to original sources

PubMed2005

Chronic heart failure with preserved left ventricular ejection fraction: diagnostic and prognostic value of left atrial size.

BACKGROUND: Almost 40% of patients with heart failure (HF) have preserved left ventricular (LV) ejection fraction (EF) and prognosis similar to those with reduced EF. Data on prognostic markers in such patients are limited. We analyzed the prevalence and prognostic value of left atrial (LA) size in this condition. METHODS: 89 normal subjects (Group I), 38 asymptomatic hypertensive patients (Group II) and 183 HF patients with preserved EF (EF >45%) (Group III) were studied. LA diameter (LAD), LV diastolic (LVD) and systolic (LVS) dimensions and mass (LVmass) and EF were measured. E and A wave velocities and E/A were measured. The primary end point was all cause mortality in group III patients. RESULTS: Groups did not differ in age, gender or EF. Group III patients had larger LAD (4.6+-1.0 cm) compared with both Group I (3.7+/-0.6) and Group II (3.7+/-0.5 cm) (p<0.0001). A markedly enlarged (arbitrarily defined as LAD higher or equal 5 cm) had an odds ratio of 34 (95% CI 8-144) in distinguishing HF patients from normals. After a mean follow-up period of 29+/-27 months, 40 patients (21.9%) died. In Cox univariate analysis, NYHA class (HR 2.8 95% C.I. 1.8-4.3; p<0.0001), diastolic blood pressure (DBP) (HR 0.92 95% C.I. 0.88-0.96; p<0.0001), age (HR 1.059 95% C.I. 1.01-1.11; p=0.02) and LAD (HR 1.72 95% C.I. 1.27-2.3; p=0.0005) were predictors of mortality. LAD predicted survival independently of other variables. CONCLUSION: The left atrium is frequently dilated in HF patients compared with controls despite similar EF. LAD showed powerful prognostic value independent of clinical variables.

Aged↗

PubMed2005

C-reactive protein in heart failure: prognostic value and the effect of valsartan.

BACKGROUND: The role of C-reactive protein (CRP) in heart failure is not well studied. We assessed the prognostic value of CRP in patients randomized in Val-HeFT (Valsartan Heart Failure Trial) and studied changes in CRP that were associated with valsartan. METHODS AND RESULTS: Characteristics of patients with baseline CRP levels above and below the median value were compared. Univariable and multivariable Cox proportional hazards regression models were used to examine the relationship of CRP to mortality and morbidity. Interactions were tested to determine whether differences in CRP changes from baseline to 4 and 12 months between groups randomly assigned to valsartan or placebo depended on baseline ACE inhibitor use. Median plasma CRP was 3.23 mg/L (interquartile range 1.42 to 7.56 mg/L), which is higher than in the general population. Patients with CRP above the median had features of more severe heart failure than those with CRP levels below the median. The cumulative likelihood of death and first morbid event increased with increasing quartile of CRP. Relative to the lowest CRP quartile, the risk of mortality (hazard ratio 1.51, 95% CI 1.2 to 1.9) and first morbid event (hazard ratio 1.53, 95% CI 1.28 to 1.84) was increased in the highest CRP quartile in multivariable models. CRP added incremental prognostic information to that provided by brain natriuretic peptide alone. CRP did not change significantly over time in the placebo group; however, after 12 months, valsartan was associated with a decrease in CRP in patients not receiving ACE inhibitors but not in those receiving ACE inhibitors at 12 months. CONCLUSIONS: CRP is increased in heart failure. Higher levels are associated with features of more severe heart failure and are independently associated with mortality and morbidity. The ability of treatments to reduce CRP levels and the prognostic importance of reducing CRP require further study.

Aged↗

PubMed2005

Anemia and change in hemoglobin over time related to mortality and morbidity in patients with chronic heart failure: results from Val-HeFT.

BACKGROUND: Anemia is known to be a prognostic marker for patients with heart failure. However, little is known about the prognostic value of changes in hemoglobin (Hgb) over time or about the causes of anemia. METHODS AND RESULTS: Retrospective analysis of Valsartan Heart Failure Trial data indicated that the quartile of patients with the biggest average decrease in Hgb over 12 months (from 14.2 to 12.6 g/dL) had significantly (P< or =0.01) increased risk of subsequent hospitalization (hazard ratio [HR], 1.47), morbid events (HR, 1.41), and death (HR, 1.6) compared with the quartile that exhibited little change in Hgb over 12 months (from 13.7 to 13.8 g/dL). Increasing Hgb was significantly associated with lower mortality in patients with (HR, 0.78) and without (HR, 0.79) anemia at baseline. Anemia at baseline and the changes in Hgb were independently associated with serum albumin, blood pressure, glomerular filtration rate, B-type natriuretic peptide, and C-reactive protein. Lack of anemia at baseline and increases in Hgb over 12 months were not associated with smaller left ventricular diameters or higher ejection fractions. CONCLUSIONS: Changes in Hgb over 12 months were inversely associated with subsequent risk of mortality and morbidity, independently of the effects of baseline anemia and other important predictors. Several factors were independently related to anemia at baseline and changes in Hgb, suggesting multiple causes of anemia in patients with heart failure. These findings raise important questions about the optimal level of Hgb in patients with moderate to severe heart failure and how to achieve them.

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PubMed2004

Wasting of the left ventricle in patients with cardiac cachexia: a cardiovascular magnetic resonance study.

BACKGROUND: The "cachectic heart" has been described as a pathologic decrease in the size and mass of the heart, but no in vivo studies have shown changes in cardiac dimensions or left ventricular (LV) mass over time in chronic heart failure (CHF) associated with body wasting (cardiac cachexia). Cardiovascular magnetic resonance (CMR) has high reproducibility and is more sensitive than other techniques. METHODS: CMR studies of LV volumes and mass were performed at baseline and a mean of 15 months later in nine CHF patients with cardiac cachexia and 28 matched CHF controls without cachexia (mass index 23 +/- 1 vs. 29 +/- 5 kg/m2, P=0.0005). RESULTS: At baseline, LV end-diastolic volume (197 +/- 78 vs. 203 +/- 65 ml), end-systolic volume (131 +/- 75 vs. 126 +/- 63 ml), LV mass (213 +/- 44 vs. 222 +/- 62 g), and LV ejection fraction (38 +/- 19% vs. 40 +/- 16%) did not differ between cachectic patients and controls (all P>0.10). During follow-up, there was a significant decrease in LV mass in patients with cachexia (-16 g, P<0.05) and a trend to increase in LV mass in patients without cachexia (+7 g, P=0.12, comparison between groups: P=0.010). CONCLUSIONS: The direction of changes over time in LV mass differs in CHF patients with cachexia as compared with non-cachectic controls. A significant decrease in LV mass occurs in patients with cardiac cachexia. This study documents in vivo the occurrence of wasting of the left ventricle in patients with CHF who demonstrate general body wasting.

Aged↗

PubMed2002

Surrogate end points in heart failure.

Because of the increasing number of pharmacologic strategies available for treatment of heart failure (HF), the time has come to reassess the adequacy of end points used to evaluate therapeutic efficacy. Interest in the use of surrogate end points in clinical studies is increasing. A surrogate end point is defined as a measurement that can substitute for a true end point for the purpose of comparing specific interventions or treatments in a clinical trial. A true end point is one that is of clinical importance to the patient (e.g., mortality or quality of life), whereas a surrogate end point is one biologically closer to the disease process (e.g., ejection fraction or left ventricular volume in HF). The prime motivation for the use of a surrogate end point concerns the possible reduction in sample size or trial duration. Such reductions have important cost implications and in some cases may influence trial feasibility. Another, perhaps more important, aspect of measuring surrogate end points is that they increase our understanding of the mechanism of action of drugs and thus may help physicians to take a more enlightened approach in managing their patients. In this article we have analyzed the possible potentials of the surrogate end points in clinical studies of patients with chronic HF. Other uses of possible surrogates are discussed, and the limitations in finding true surrogates are mentioned. At this time we conclude there is no well established surrogate in HF.

Biomarkers↗

PubMed2002

Insulin resistance in moderate chronic heart failure is related to hyperleptinaemia, but not to norepinephrine or TNF-alpha.

OBJECTIVES: Chronic heart failure (CHF) has emerged as an insulin-resistant state, independently of ischaemic aetiology. The underlying mechanisms of this finding are not known. Catecholamines, tumor necrosis factor alpha (TNFalpha) and leptin, the adipocyte specific hormone, have all been implicated as mediators of impaired insulin sensitivity. The purpose of this study was to examine in patients with CHF and in comparison to healthy controls subjects whether norepinephrine, TNFalpha or leptin relate to insulin sensitivity. DESIGN: 41 patients with CHF (age 60+/-2 years, NYHA I/II/III/IV 4/12/22/3, peak oxygen consumption 17.6+/-1.0 ml/kg per min) and 21 healthy controls of similar age and total and regional fat distribution were studied in a cross-sectional study. Insulin sensitivity was assessed by intravenous glucose tolerance testing using the minimal model approach; catecholamines, TNFalpha and soluble TNF receptors 1 and 2 were also measured. Total and regional body fat mass was assessed by dual energy X-ray absorptiometry. RESULTS: Insulin sensitivity was reduced in CHF patients compared to controls by 31% (P<0.01) and fasting insulin was higher in patients than in controls (79.1+/-9.7 vs. 41.4+/-6.0 pmol/l, P<0.01). Patients had, compared to healthy controls, elevated serum leptin levels (8.28+/-0.84 vs. 4.83+/-0.68 ng/ml), norepinephrine (3.45+/-0.34 vs. 1.87+/-0.16 nmol/l, both P<0.01) and soluble TNF-receptors 1 (1280+/-141 vs. 639+/-52 pg/ml) and 2 (2605+/-184 vs. 1758+/-221 pg/ml, both P<0.01). Leptin levels corrected for total body fat mass were higher in CHF patients than in controls (41.3+/-3 vs. 24.3+/-2 pg/ml per 100 g, P<0.001). TNFalpha was not significantly different between the groups. In both groups there was an inverse correlation between insulin sensitivity and serum leptin (r=-0.65, P<0.0001 for pooled subjects); in contrast, no significant relation was found between insulin sensitivity and norepinephrine or TNFalpha. In multivariate regression analysis, leptin emerged as the only significant predictor of insulin sensitivity (standardised coefficient=-0.59, P<0.001), independent of body fat mass, age and peak VO2. CONCLUSION: In moderate CHF, elevated leptin levels directly and independently predict insulin resistance. Elevated serum leptin levels could play a role in the impaired regulation of energy metabolism in CHF. In contrast to observations in other conditions, TNFalpha and norepinephrine are not related to insulin resistance in moderate CHF.

Adipose Tissue↗

PubMed2002

Noninvasive assessment of left ventricular remodeling: concepts, techniques, and implications for clinical trials.

BACKGROUND: Over the past decade, our understanding of the cellular and biochemical mechanisms that underlie global changes in ventricular morphology and function has grown enormously. Nevertheless, although the sequence of events that lead to overt changes in the ventricle begin at the cellular level, in living patients we rarely have the opportunity to assess these phenomena as they occur. Thus, to study the process of remodeling in practice and in clinical trials, we have relied on assessments and measurements derived from cardiac imaging tests. METHODS AND RESULTS: Since the initial angiographic based methods for assessing ventricular remodeling in humans, a variety of techniques has been developed that have been used for assessment of ventricular size, shape, and function for both clinical and research studies. As two-dimensional echocardiography has emerged as the predominant noninvasive diagnostic method for clinical use in evaluating left ventricular function, this modality has become the most widely used technique to assess ventricular remodeling. Nevertheless, nuclear techniques that have proven both reliable and highly reproducible have also been used in clinical and research setting and, more recently, cardiac magnetic resonance imaging has offered the potential to obtain extremely high-quality images of the heart at much higher resolution than either of the other techniques. CONCLUSIONS: Each of these techniques carries specific advantages and disadvantages for assessment of remodeling in individual patients and in the context of large-scale clinical trials.

Clinical Trials as Topic↗

PubMed2002

The cardiac component of cardiac cachexia.

BACKGROUND: Recent evidence suggests the importance of noncardiac mechanisms in the genesis of the syndrome of cardiac cachexia. This raises the question of the relative role of the heart itself in this syndrome. This study sought to assess the cardiac dimensions, mass, and function and changes in these parameters over time in patients with chronic heart failure with and without cachexia. METHODS: Doppler echocardiography was performed in 28 patients with nonedematous weight loss (>7.5% over a period of >6 months) compared with 56 matched patients without weight loss in a ratio of 1:2 (age 71 +/- 13 vs 67 +/- 8 years, P =.07; New York Heart Association class 2.9 +/- 0.7 vs 2.6 +/- 0.6, P =.08). In 18 cachectic and 35 noncachectic patients with previous echocardiographic recordings, we analyzed the changes in left ventricular (LV) dimensions and mass over time. RESULTS: Cardiac dimensions including LV diastolic (69 +/- 9 mm vs 67 +/- 13 mm) and systolic cavity diameter (58 +/- 11 mm vs 55 +/- 15 mm), LV mass (480 +/- 180 g vs 495 +/- 190 g), and LV systolic and diastolic function including fractional shortening (16% +/- 10% vs 18% +/- 10%), isovolumic relaxation time (29 +/- 22 ms vs 36 +/- 27 ms), and E/A ratio (2.7 +/- 1.6 vs 3.3 +/- 2.9) did not differ between cachectic and noncachectic patients (all P >.1). By analyzing changes in LV mass over time, we found an increase (>20%) in 2 (11%) cachectic and 14 (40%) noncachectic patients and a decrease in LV mass (>20%) in 9 (50%) cachectic and 8 (23%) noncachectic patients (chi2 test, P <.05). CONCLUSIONS: Although no specific cardiac abnormality could be detected echocardiographically in cachectic patients compared with patients with noncachectic chronic heart failure in a cross-sectional study, over time a significant loss of LV mass (>20%) occurs more frequently in patients with cardiac cachexia.

Cachexia↗