Maria A.E. Rao

Blood levels of erythropoietin in congestive heart failure and correlation with clinical, hemodynamic, and hormonal profiles

Plasma levels of erythropoietin (mU/ml) were measured in patients with congestive heart failure (CHF) (n = 108) and in a control group of normal subjects (n = 45). In normal subjects, plasma levels of erythropoietin were 1.9 +/- 0.2. In patients with CHF, plasma levels of erythropoietin increased progressively according to New York Heart Association (NYHA) class (I: 1.4 +/- 0.2, n = 28; II: 5.4 +/- 0.8, n = 27; III: 9.6 +/- 2, n = 32; IV: 34 +/- 8, n = 21; F = 57.7, p < 0.001) and were significantly higher in NYHA classes II, III, and IV than in normal subjects. Plasma erythropoietin significantly decreased (from 43 +/- 14 to 12 +/- 3 mU/ml, p < 0.01) in patients with severe CHF (n = 9) when enalapril (20 mg/day administered orally) was added to long-term treatment for 3 weeks. Finally, in a subgroup of patients with NYHA class IV CHF (n = 9) and high plasma erythropoietin levels (37 +/- 9 mU/ml), packed red blood cell volume, assessed by the iodine-125-albumin dilution method, was higher than that in normal subjects (n = 11) (2,616 +/- 235 vs 2,028 +/- 119 ml, p < 0.05). The present study demonstrates that plasma erythropoietin levels are elevated in a large cohort of patients with CHF of varying etiology, and that this increase is related to the progression of the disease. The increase in circulating erythropoietin is associated with augmented packed red blood cell volume in patients with severe CHF. These results suggest a participation of erythropoietin in the complex neurohormonal response that occurs in CHF.

Independent and incremental prognostic value of heart rate variability in patients with chronic heart failure

BACKGROUND Decreased heart rate variability (HRV), indicating derangement in cardiac autonomic control, has been reported in patients with chronic heart failure. However, the independent and incremental prognostic value of HRV over clinical data and measures of left ventricular dysfunction has been less thoroughly investigated. This study was designed to evaluate the predictive value of HRV and Poincaré plots as assessed by 24-hour Holter recording in patients with chronic heart failure. METHODS Ninety-seven patients, mean age 55 +/- 13 years, with radionuclide left ventricular ejection fraction </=40% underwent echocardiographic examination and 24-hour Holter recording. Heart failure was caused by coronary artery disease in 57 patients (59%) and idiopathic dilated cardiomyopathy in 40 (41%). RESULTS During follow-up (39 +/- 18 months), 32 cardiac deaths occurred. By Cox multivariate analysis, significant predictors of death were left ventricular end-systolic volume (hazard ratio 1.04), low- to high-frequency ratio (hazard ratio 0.09), percentage of differences between successive normal R-R intervals >50 ms (hazard ratio 0.93), and age (hazard ratio 1.06). Furthermore, HRV analysis improved (P <. 001) the prognostic power of a model including clinical and echocardiographic data, left ventricular ejection fraction, and ventricular arrhythmias at Holter recording, whereas the inclusion of Poincaré plots did not add further predictive value. CONCLUSIONS Our investigation demonstrated that HRV has independent and incremental prognostic value in patients with chronic heart failure and seems useful to stratify patients at high risk of cardiac death.

Early Impairment of Renal Hemodynamic Reserve in Patients With Asymptomatic Heart Failure Is Restored by Angiotensin II Antagonism

BACKGROUND The early/asymptomatic stages of heart failure (HF) are characterized by sodium retention secondary to derangement of sodium reabsorption at the proximal nephron level. Because this phenomenon is reversed by ACE inhibition, abnormalities of renal sodium handling may depend on intrarenal changes of angiotensin II (AII)/nitric oxide (NO) levels. Renal hemodynamic reserve (ie, the glomerular vasodilatory response to amino acid infusion) has been proposed as a reliable test to assess in vivo AII/NO balance. METHODS AND RESULTS In this study, the effects of 6 weeks of treatment with 5 mg/d of enalapril or with 50 mg/d of losartan on systemic hemodynamics and renal function were assessed, at baseline and after amino acid infusion (AA), in patients with mild HF (NYHA class I) and in healthy volunteers. Untreated HF patients showed a basal renal function comparable to that of healthy subjects. After AA, glomerular filtration rate and renal plasma flow significantly increased in healthy subjects (+29.0% and +30.4%, respectively), whereas no vasodilatory response was observed in HF. Although they did not affect basal renal hemodynamics, both enalapril and losartan restored a normal response to AA in HF patients. Blood pressure and heart rate were comparable in HF subjects and healthy subjects at baseline and were not modified by either treatment. Left ventricular ejection fraction was depressed in HF but did not change after either drug. Urinary excretions of cGMP and nitrate (indexes of NO activity in the kidney), comparable in healthy subjects and in HF patients, were unchanged by either enalapril or losartan and did not correlate with renal reserve. CONCLUSIONS (1) Renal functional reserve is absent in patients with early/asymptomatic HF and normal renal function and (2) both enalapril and losartan restore a normal vasodilatory response to AA in these patients without affecting basal systemic and renal hemodynamics. These data suggest a major role of AII in the development of early abnormalities in patients with HF.

Intrarenal Determinants of Sodium Retention in Mild Heart Failure Effects of Angiotensin-Converting Enzyme Inhibition

The onset and the mechanisms leading to Na+ retention in incipient congestive heart failure (CHF) have not been systematically investigated. To investigate renal Na+ handling in the early or mild stages of CHF, Na+ balance and renal clearances were assessed in 10 asymptomatic patients with idiopathic or ischemic dilated cardiomyopathy and mild heart failure (HF) off treatment (left ventricular ejection fraction, 29.7+/-2%) and in 10 matched normal subjects during a diet containing 100 mmol/d of NaCl and after 8 days of high salt intake (250 mmol/d). Six patients were studied again after 6 weeks of treatment with enalapril (5 mg/d P.O.). At the end of the high salt diet, in patients with mild HF the cumulative Na+ balance exceeded by 110 mmol that of normal subjects (F=3.86, P<.001). During high salt intake, renal plasma flow and glomerular filtration rate were similarly increased in both normal subjects and mild HF patients. In spite of comparable increases of filtered Na+ in the two groups, fractional excretion of Na+, fractional clearance of free water, and fractional excretion of K+ (indexes of distal delivery of Na+) increased in normal subjects and were reduced in patients with mild HF. During enalapril treatment, in the mild HF patients the cumulative Na+ balance was restored to normal; furthermore, enalapril significantly attenuated the abnormalities in the distal delivery of Na+. Our results indicate that a defective adaptation of Na+ reabsorption in the proximal nephron is associated with Na+ retention in response to increased salt intake in the early or mild stages of HF. These abnormalities of renal Na+ handling are largely reversed by enalapril.

Radionuclide Monitoring of Cardiac Adaptations to Volume Loading in Patients With Dilated Cardiomyopathy and Mild Heart Failure: Effects of Angiotensin-Converting Enzyme Inhibition

BACKGROUND Cardiac adaptations to volume overload have been poorly investigated in heart failure. The aim of this study was to assess dynamic left ventricular responses to acute volume loading by continuous radionuclide monitoring in patients with asymptomatic to mildly symptomatic left ventricular dysfunction. METHODS AND RESULTS Left ventricular end-diastolic (EDV) and end-systolic (ESV) volumes, ejection fraction (EF), and peak filling rate (PFR) were monitored by a radionuclide detector (Vest) before and during volume expansion (sodium chloride, 0.9%, 0.25 mL.kg-1.min-1 for 2 hours) in 10 patients with idiopathic dilated cardiomyopathy (DCM) and mild heart failure (New York Heart Association class I or II, ejection fraction < 50%). The patients were studied off treatment and after 6 to 8 weeks of oral treatment with enalapril (5 mg/d). A control group of 11 age- and sex-matched healthy volunteers (N group) was also studied. In the N group, volume loading caused prompt and sustained increases of EDV, EF, and PFR (all P < .001), whereas ESV was progressively reduced (P < .001), and heart rate and blood pressure did not change. In contrast, in DCM, EDV showed a smaller increase than in the N group (two-way ANOVA: F = 5.98, P < .001), ESV increased (P < .001), and EF and PFR remained unchanged. After enalapril, the cardiac adaptations to volume loading were restored to normal. In particular, EDV, EF, and PFR increased (P < .001), and ESV was reduced (P < .001). In 6 additional DCM patients studied before and after 6 to 8 weeks of placebo treatment, left ventricular responses to volume loading remained unchanged. CONCLUSIONS Left ventricular dynamic adaptations to acute volume loading are compromised in patients with idiopathic DCM and mild heart failure. These impaired responses are ameliorated by treatment with enalapril.

Transition from asymptomatic left ventricular dysfunction to congestive heart failure

One of the main goals of modern management and care of heart failure is to prevent the disease to progress toward congestion and death. The achievement of such an objective may, in fact, guarantee a sufficient quality of life and reduce the exposure of patients to the most common life-threatening complications associated with the congestive stage of the disease. Early identification of left ventricular dysfunction as well as a better knowledge of the mechanisms that favor the progression to more advanced stages of heart failure are fundamental requirements for the proper treatment of asymptomatic heart failure and for preventing the transition to symptomatic and more severe heart failure. The authors reviewed the literature on this topic, with emphasis on a series of studies they performed, to characterize the pathophysiologic profile of mild heart failure and the mechanisms that are possibly involved in the progression to congestive heart failure.

Long-term effects of felodipine in patients with mild heart failure treated chronically with enalapril: A randomized, placebo-controlled study

Abstract Although the introduction of angiotensin-converting enzyme (ACE) inhibitors in the treatment of congestive heart failure has led to improved management and outcome of the disease, the progression of ventricular dysfunction remains a major problem. The present study was designed to examine the long-term effects of felodipine, a calcium channel blocker, on the progression of ventricular dysfunction in patients with mild ischemic heart failure treated chronically with the ACE inhibitor enalapril. A total of 23 patients with a history of myocardial infarction and mild heart failure (New York Heart Association [NYHA] functional class I or II; mean ejection fraction, 30.5 ± 1.6%), who had received long-term treatment with enalapril 5 to 10 mg/d, were randomized to receive felodipine 5 mg/d (n = 12) or placebo (n = 11) for 12 months. At baseline, the study groups had similar hemodynamic and clinical characteristics as well as similar hormonal profiles. In contrast, during the study, ejection fraction decreased progressively from 30.1 ± 1.9% to 29.6 ± 1.9% in the placebo group but increased progressively from 30.8 ± 2.5% to 36.3 ± 2.1% in the felodipine group. Consistently, plasma atrial and brain natriuretic peptide levels were higher at 12 months in the placebo group than in the felodipine group. At baseline and at 12 months, 2 patients were in NYHA class I and 9 patients in class II in the placebo group; in the felodipine group, 4 patients were in class I and 8 patients in class II at baseline, and 7 patients in class I and 5 patients in class II at 12 months. Left ventricular adaptations to volume loading measured after 3 months of treatment were significantly improved only in the felodipine group. Similarly, peak oxygen consumption during cardiopulmonary testing increased significantly only in the felodipine group. These results show that the long-term addition of felodipine to treatment with ACE inhibitors significantly improves ventricular function and may reduce the progression of disease in patients with mild ischemic heart failure.

A Rare Case of Hypertension

A 61-year-old female was referred to our hypertension centre for uncontrolled hypertension. She had been previously diagnosed with type 2 diabetes mellitus and impaired serum lipid profile. At admission, she assumed β-adrenoceptor antagonists (β-blockers) and calcium antagonists; she had uncontrolled blood pressure levels and she presented with a recent episode of headache associated with syncope and showed negative cerebral CT. Examinations performed in our hypertension outpatient clinic (physical examination, blood biochemistry, instrumental diagnosis and screening for secondary hypertension) had negative outcomes. Average blood pressure on three different determinations was above the normal values. A modification in antihypertensive therapy was performed with no results. During a follow-up visit, the patient lost consciousness. She was promptly transferred to the Cardiac Intensive Care Unit. During the following diagnostic iter (cerebral CT and urinary catecholamine levels based on a 24-hour sample), cerebral MRI evidenced malformation of Arnold Chiari type I. The neurological surgery consultant advised surgical procedure with occipital decompression technique. One year later the patient underwent surgical intervention. The patient actually reports suboptimal control of blood pressure. To date, no episode of transitory coma has occurred.