David Sheps

Circulating adiponectin concentrations in patients with congestive heart failure

Objectives: To determine concentrations of adiponectin and its predictive value on outcome in a cohort of patients with congestive heart failure (CHF). Methods: Serum and clinical data were obtained for outpatients with clinically controlled CHF (n  =  175). Serum concentrations of adiponectin, C reactive protein, N-terminal pro-brain natriuretic peptide (NT-proBNP), interleukin (IL) -1β, IL-6, IL-8, IL-10, IL-12, tumour necrosis factor α and CD-40 ligand were determined. The association of adiponectin with the clinical severity of CHF was sought as well as the predictive value of this adipokine on mortality, CHF hospitalisations or the occurrence of each of these end points. Results: Concentrations of adiponectin were significantly increased in patients with CHF. Patients with higher New York Heart Association class had significantly higher serum concentrations of adiponectin. Adiponectin serum concentrations were lower in patients with diabetes and CHF as well as in patients with ischaemic cardiomyopathy. Serum adiponectin concentration was positively associated with age and NT-proBNP but was negatively correlated with C reactive protein concentrations. Serum adiponectin above the 75th centile was found to be an independent predictor of total mortality, CHF hospitalisations or a composite of these end points over a two-year prospective follow up. Conclusion: Adiponectin is increased in CHF patients and predicts mortality and morbidity.

Effects of Treatment with Epoetin Beta on Outcomes in Patients with Anaemia and Chronic Heart Failure

Anaemia is frequently found in patients with chronic heart failure (CHF) and has been associated with an increase in mortality and morbidity, impaired cardiac and renal function and a reduced quality of life (QoL) compared with non-anaemic CHF patients. Correction of anaemia with recombinant human erythropoietin (epoetin) has been associated with an improvement in CHF in both controlled and uncontrolled studies. The present study describes our findings in a series of 78 consecutive patients with symptomatic CHF and anaemia (haemoglobin (Hb) level <12.0 g/dl) treated with epoetin beta and, if necessary, intravenous iron sucrose. Over a mean observation period of 20.7 ± 12.1 months, mean Hb levels increased from 10.2 ± 1.1 to 13.5 ± 1.2 g/dl, p < 0.01. New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF) were significantly improved and the number of hospitalizations was significantly reduced with the period before treatment (all p < 0.01). Serum creatinine and creatinine clearance (CCr) were 2.2 ± 0.9 mg/dl and 32.5 ± 26.5 ml/min, respectively, at baseline, and remained stable over the observation period. Interestingly, >90% of the patients had concomitant mild-to-moderate chronic kidney disease at baseline and study end (CKD), as defined by the accepted diagnostic criterion of a CCr <60 ml/min. Conclusions: The correction of the anaemia with epoetin beta together with initial intravenous iron supplementation, resulted in significant improvements in NYHA class and cardiac function, and a reduction in hospitalization rate. Moreover, renal function was maintained stable in most patients.

Usefulness of anti-oxidized LDL antibody determination for assessment of clinical control in patients with heart failure.

It has been suggested that oxidative stress may play a role in the pathogenesis of heart failure, this may have potential implications for therapeutic strategies. However, measures of oxidative stress are subject to confounding inaccuracies. IgG antibodies to oxidized LDL reflect exposure to the lipoprotein over an extended period and may thus mirror oxidative stress over a prolonged time frame. Therefore, we tested the hypothesis that anti‐oxLDL antibodies correlate with the control of heart failure (HF), as manifested by hospital admissions for cardiac dysfunction.

Baseline Low-Density Lipoprotein Cholesterol Levels and Outcome in Patients With Heart Failure

The incidence of heart failure (HF) is constantly increasing in the Western world. Treatment with statins is well established for the primary and secondary prevention of cardiac events by lowering low-density lipoprotein (LDL) cholesterol levels. There are conflicting reports on the role of LDL cholesterol as an adverse prognostic predictor in patients with advanced HF. The aim of this study was to investigate the association between LDL cholesterol levels and clinical outcomes in 297 patients with severe HF (average New York Heart Association class 2.8). The mean follow-up period was 3.7 years (range 8 months to 11.5 years), and 37% of the patients died during follow-up. The mean time to first hospital admission for HF was 25 +/- 17 months. The study group was divided according to plasma LDL level < or =89, >89 to < or =115, >115 mg/dl. Patients with the highest baseline LDL cholesterol levels had significantly improved outcomes, whereas those with the lowest LDL cholesterol levels had the highest mortality. When analyzed with respect to statin use, it emerged that the negative association between LDL cholesterol level and mortality was present only in the patients with HF who were treated with statins. In conclusion, lower LDL cholesterol levels appear to predict less favorable outcomes in patients with HF, particularly those taking statins, raising questions about the need for aggressive LDL cholesterol-lowering strategy in patients with HF, regardless of its cause.

Usefulness of Total Lymphocyte Count as Predictor of Outcome in Patients With Chronic Heart Failure

Low lymphocyte count has been considered a predictive marker of unfavorable outcomes for patients with heart failure (HF). Baseline blood samples for complete blood counts, differential counts, renal function tests. and lipid profile were prospectively obtained to assess the association between lymphocyte count and clinical outcomes in 305 patients with HF (average New York Heart Association [NYHA] class 2.8). The mean follow-up duration was 4.7 years (range 8 months to 8.4 years), and 111 patients (36%) died during the follow-up period. The mean lymphocyte count for the group was 1,803.64 ± 740.3, and the mean left ventricular ejection fraction (LVEF) was 37%. Patients with low lymphocyte counts (<1,600 median count) after 8 years had significantly lower survival rates than those with lymphocyte counts ≥1,600 (58% vs 72%, p=0.012). The prediction of poorest survival was for patients in NYHA class III or IV and with lymphocyte counts <1,600. Regression analysis showed that lymphocyte level, the LVEF, and NYHA class were predictors of mortality. Of these, NYHA class was the most prominent predictor, followed by lymphocyte count, which was even more significant than the LVEF (hazard ratio 0.76, p=0.037). In conclusion, the findings of this study demonstrate that total lymphocyte count is an important prognostic factor, inversely associated with predicted mortality. Although the total low lymphocyte count was correlated with a lower NYHA class and a lower LVEF, it emerged as an independent death risk factor in patients with chronic HF.

Serum lipids and restenosis after successful percutaneous transluminal coronary angioplasty

Abstract The effects of plasma lipids on the clinical and angiographic parameters of 134 patients, in whom coronary angioplasty was performed in 157 vessels, were prospectively examined. During a 6-month follow-up, restenosis was detected angiographically in 39 patients (29%; 45 vessels). None of the clinical, biochemical, or angiographic variables examined was predictive of stenosis and the tendency of a vessel to restenose was not patient-dependent but rather lesion-related. However, restenosis developed in 31 of 102 vessels (30%) in patients with high-density lipoprotein (HDL) cholesterol ⩽ 40 mg/dl, compared with restenosis in 10 of 55 vessels (19%) in patients with HDL cholesterol >40 mg/dl (p = 0.092). No significant differences were observed when restenosis rates were compared in patients with total cholesterol levels >250 mg/dl or 160 mg/dl and

Antibodies to Oxidized LDL as Predictors of Morbidity and Mortality in Patients With Chronic Heart Failure

BACKGROUND Oxidative stress appears to play a significant role in the pathogenesis of heart failure (HF). Antibodies to oxidized low-density lipoprotein (Ox LDL Abs) reflect an immune response to LDL over a prolonged period and may thus represent oxidative stress over an extended time. Ox LDL Abs have been shown to correlate with clinical control in HF patients. We evaluated the predictive power of Ox LDL Abs on the outcome in patients with HF. METHODS AND RESULTS Baseline levels of Ox LDL Abs were determined by enzyme-linked immunosorbent assay in 284 consecutive outpatients with severe chronic HF who were being treated in the cardiology services of our medical center. Their mean New York Heart Association (NYHA) Class was 2.8. The mean follow-up for the group was 3.7 years, during which 107 (37%) died. The mean time from symptom onset to first hospital admission from HF was 25.8 months. Ox LDL Abs were found to predict morbidity and mortality as evaluated by a Cox multivariate regression analysis with a hazard ration of 1.013 (P < .013), whereas N-terminal pro-B-type natriuretic peptide (NT pro-BNP) levels achieved a HR of 1.028 (P < .099). CONCLUSIONS Ox LDL Abs level maybe a useful parameter for monitoring and planning better management of patients with HF. It was superior to pro-BNP as a predictor of clinical course as expressed by time to hospitalization.

Detection of Restenosis following Percutaneous Coronary Angioplasty in Single-Vessel Coronary Artery Disease: The Value of Clinical Assessment and Exercise Tolerance Testing

Chest pain and submaximal exercise testing were prospectively assessed over a 6-month period, for detecting the evolution of restenosis in patients undergoing percutaneous coronary angioplasty, following either acute myocardial infarction or treatment of an anginal syndrome. Seventy-eight patients with one-vessel coronary artery disease underwent a modified treadmill exercise test at the 1-week, 3-month and 6-month follow-up after angioplasty, when a final angiogram was also performed. Forty-four patients (group A) were examined after myocardial infarction; in 34 patients (group B) angioplasty was done for incapacitating angina. Both groups showed similar results with low sensitivity and relatively moderate specificity of both chest pain and exercise tests; this was also the case for the time of restenosis to occur. It is thus concluded that the parameters examined are somewhat limited markers of restenosis following coronary angioplasty.

The importance of correction of anemia with erythropoietin and intravenous iron in severe resistant congestive heart failure

About one third to one half of patients with heart failure are anemic, in that they have a hemoglobin level of less than 12 g/dL. Anemia is more common and more severe as the clinical status of CHF worsens. In addition, anemia is associated with a higher mortality and higher rate of hospitalization, as well as with signs of malnutrition. In anemic CHF patients who are resistant to maximally tolerated CHF medications and who remain very symptomatic, both uncontrolled studies of a combination of subcutaneous erythropoietin (EPO) and IV ferric sucrose have reported a correction of the anemia. This correction has been associated with an improvement in NYHA functional status, left ventricular ejection fraction, and a marked reduction in the doses of diuretic needed and in the frequency and duration of hospitalizations. Renal function, which had been steadily falling before the correction of the anemia, was also stabilized. Other controlled studies have also found that anemia correction with EPO increased oxygen utilization during maximal exercise, exercise endurance and quality to life. The anemia is probably due mainly to a combination of renal failure and excessive cytokines, both of which interfere with EPO production and utilization. If confirmed by larger studies, correction of anemia with the EPO-IV iron combination may become a useful adjuvant to the treatment of CHF.

Right Bundle Branch Block of Unknown Age in the Setting of Acute Anterior Myocardial Infarction: An Attempt to Define Who Should Be Paced Prophylactically

It is widely accepted that patients presenting with acute anterior myocardial infarction and acute onset of right bundle branch block should be prophylactically paced in contrast with those who have a chronic bundle branch block. The admitting physician is faced with the dilemma of how to act if the age of this conduction disturbance is unknown. This problem has further intensified in recent years, with the introduction of thrombolytic treatment, where insertion of a central vascular line is associated with increased morbidity. The objectives of this study were to define clinical or electrocardiographic parameters that may help the admitting physician to decide whether patients presenting with an anterior wall myocardial infarction and a right bundle branch block of unknown age should be prophylactically paced. We examined prospectively the in‐hospital clinical course of 39 consecutive patients presenting with an acute myocardial infarction in whom the age of a right bundle branch block upon admission was unknown (group C, n = 39) and compared it with two similar groups of patients who presented with an acute right bundle branch block (group A, n = 38) and with a known chronic right bundle branch block (group B, n = 22). Thirty‐three patients (33%) died, with cardiogenic shock being the leading cause of death in the entire population. Prophylactic pacing, which was carried out in 66% and 54% of patients in groups A and C, respectively, did not reduce mortality rates. No clinical or electrocardiographic variables on admission were predictive to support prophylactic pacing in group C. In 10 of 46 (22%) patients who were prophylactically paced with a transvenous electrode, the following complications attributed to the procedure were detected: (1) either rapid sustained ventricular tachycardia (during implantation) that was unresponsive to overdrive pacing, or ventricular fibrillation necessitating electrical defibrillation (4 patients); (2) recurrent episodes of rapid nonsustained ventricular tachycardia, which stopped only after the pacemaker was turned off (1 patient); (3) complete AV block (1 patient); (4) fever appearing on the third or fourth day after implantation (3 patients); and (4) a large hematoma in the groin in 1 patient who was treated with thrombolysis shortly before pacemaker electrode insertion. Thus, the complications of transvenous temporary pacing in the era of thrombolysis may outweigh any theoretical advantage. (PACE 1995; 18:1496‐1508)