Background and Methods. Although cachexia often accompanies advanced heart failure, little is known about the causes of the cachectic state. To assess the potential role of tumor necrosis factor in the pathogenesis of cardiac cachexia, we measured serum levels of the factor in 33 patients with chronic heart failure, 33 age-matched healthy controls, and 9 patients with chronic renal failure. Results. Mean (±SEM) serum levels of tumor necrosis factor were higher in the patients with heart failure (115±25 U per milliliter) than in the healthy controls (9±3 U per milliliter; P 2 SD above the mean value for the control group), whereas the remaining 14 patients had serum levels of tumor necrosis factor below this level. The patients with high levels of tumor necrosis factor were more cachectic than those with low levels (82±3 vs. 95±6 percent of ideal body weight, respectively; P...

https://www.nejm.org/doi/pdf/10.1056/NEJM199007263230405

Elevated Circulating Levels of Tumor Necrosis Factor in Severe Chronic Heart Failure

Neurohumoral modulation of cardiovascular function is an important component of the hemodynamic alterations in patients with chronic congestive heart failure (CHF). Analysis of heart rate (HR) variability is a noninvasive means of investigating the autonomic control of the heart. The variability of HR and respiratory signals, both derived from ambulatory electrocardiographic recordings, were analyzed with power spectral analysis to evaluate autonomic control in 25 patients with chronic stable CHF (class III or IV) and 21 normal control subjects. In the patients with CHF, HR spectral power was markedly reduced (p less than 0.0001) at all frequencies examined (0.01 to 1.0 Hz, period 1 to 100 seconds) and virtually absent at frequencies greater than 0.04 Hz. Heart rate fluctuations at very low frequencies (0.01 to 0.04 Hz) less effectively differentiated CHF patients from control subjects, due to discrete (about 65 seconds, 0.015 Hz) oscillation in HR, which was associated with a similar pattern in respiratory activity in many of the patients with CHF. These findings demonstrate a marked derangement of HR modulation in patients with severe CHF. The frequency characteristics of HR fluctuations in these patients are consistent with abnormal baroreflex responsiveness to physiologic stimuli, and suggest that there is diminished vagal, but relatively preserved sympathetic, modulation of HR.

Assessment of autonomic regulation in chronic congestive heart failure by heart rate spectral analysis.

Aims Hyponatraemia has been shown to be an independent predictor of mortality in selected patients with heart failure enrolled in clinical trials. The predictive value of hyponatraemia has not been evaluated in unselected patients hospitalized with heart failure.

Methods and results OPTIMIZE-HF is a registry and performance-improvement programme for patients hospitalized with heart failure and includes a subgroup with 60–90 day follow-up data. The relationship between admission serum sodium concentration and clinical outcomes was analysed in 48 612 patients from 259 hospitals. Admission serum sodium levels were analysed both as a continuous variable and by grouping patients with admission Na <135 and Na ≥ 135 mmol/L. Patients with hyponatraemia (Na <135 mmol/L) at the time of hospital admission had modest differences in baseline clinical characteristics and management during hospitalization compared with patients who had serum sodium ≥135 mmol/L. Patients with hyponatraemia were more likely to be Caucasian, have lower admission systolic blood pressure, and receive intravenous inotropes during hospitalization. Patients with hyponatraemia had significantly higher rates of in-hospital and follow-up mortality and longer hospital stays, although no difference in re-admission rates was observed. After adjusting for differences with multivariable analysis, the risk of in-hospital death increased by 19.5%, the risk of follow-up mortality by 10%, and the risk of death or rehospitalization by 8% for each 3 mmol/L decrease in admission serum sodium below 140 mmol/L.

Conclusion Hyponatraemia in hospitalized patients with heart failure is relatively common and is associated with longer hospital stays and higher in-hospital and early post-discharge mortality. Re-admission rates were equally high in patients with or without hyponatraemia.

Relationship between admission serum sodium concentration and clinical outcomes in patients hospitalized for heart failure: an analysis from the OPTIMIZE-HF registry.

When cardiac output falls after an insult t cardium, a number of neurohormonal mecd activated to preserve circulatory homeo though originally viewed as a beneficial coI response, the endogenous release of vasc neurohormones appears to play a deleteriou development of congestive heart failure. A( the sympathetic nervous and renin-angioten causes an increase in loading conditions in ventricle and may accelerate progression of lying disease. These neurohormones may ir (and exacerbate) the electrolyte abnormalit heart failure, which may underlie the path ventricular arrhythmias. By these mechan rohormonal activation contributes importa symptoms of heart failure as well as to the tality of patients with this disorder.' Why are these neurohormones released with heart failure when their effects are so d Physiologists have hypothesized that the ci limited in its capacity to respond to circul; (e.g., a reduction in cardiac output). Accor theory, the mechanisms that are activated ir

Neurohormonal interactions and adaptations in congestive heart failure.

Background— The prognostic value of serum sodium in patients hospitalized for worsening heart failure has not been well defined. Methods and Results— The Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) study randomized 949 patients with systolic dysfunction hospitalized for worsening heart failure to receive 48 to 72 hours of intravenous milrinone or placebo in addition to standard therapy. In a retrospective analysis, we investigated the relationship between admission serum sodium and the primary end point of days hospitalized for cardiovascular causes within 60 days of randomization, as well as the secondary end points of in-hospital mortality, 60-day mortality, and 60-day mortality/rehospitalization. The number of days hospitalized for cardiovascular causes was higher in the lowest sodium quartile: 8.0 (4.5, 18.5) versus 6 (4, 13) versus 6 (4, 11.5) versus 6 (4, 12) days (P<0.015 for comparison with the lowest quartile). Lower serum sodiu...

Lower serum sodium is associated with increased short-term mortality in hospitalized patients with worsening heart failure: results from the Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) study.

To study the relationship between serum Na concentration and impairment of homeostatic mechanisms in advanced congestive heart failure (CHF), we evaluated the status of the sympathetic nervous system, renin-angiotensin system, and regional visceral blood flow in 26 patients with this syndrome. Compared with normal subjects, hyponatremic patients had marked stimulation of PRA (P = 0.012), norepinephrine (P less than 0.001), and epinephrine (P less than 0.001) with severe impairment of renal (P less than 0.001) and hepatic (P less than 0.003) plasma flows. In contrast, normonatremic patients, with an apparently similar degree of CHF, demonstrated less pronounced abnormalities in all of these parameters. Moreover, the responses of neurohormones and regional blood flow to orthostatic stress were greatly attenuated in the hyponatremic patients, whereas, the normonatremic subjects had more normal responses. We conclude that serum Na concentration serves as a useful index of activation of the sympathetic nervous system, renin-angiotensin system, and impairment of regional perfusion in patients with advanced CHF.

Linea Rydstedt

Papers

Hyponatremia in congestive heart failure: Implications for neurohumoral activation and responses to orthostasis