Citations

BackgroundRecent studies suggest that neurohumoral mechanisms including decreased renal responses to increases in atrial natriuretic factor (ANF) play a central role in the progression from asymptomatic cardiac dysfunction to advanced congestive heart failure (CHF) with sodium retention, vasoconstriction, and reduced exercise tolerance. Recognizing that neutral endopeptidase 24.11 degrades ANF and may be enhanced in CHF, we hypothesized that chronic neutral endopeptidase inhibition (NEP-I) would potentiate renal responses to exogenous ANF and alter the temporal evolution of sodium retention in evolving CHF by potentiation of increased endogenous ANF.Methods and ResultsWe studied 13 conscious dogs with evolving CHF produced by rapid ventricular pacing at 250 beats per minute. Six of these dogs received NEP-I with candoxatril, 10 mg/kg PO BID, throughout evolving CHF. Responses to exogenous ANF, 10 μg/kg IV bolus, were assessed at baseline and after 6 days of CHF. Daily metabolic studies during evolving CHF with chronic NEP-I showed increased sodium excretion and renal cGMP generation consistent with enhanced renal activity of endogenous ANF compared with untreated controls. In addition, renal natriuretic and cGMP responses to exogenous ANF were intact in CHF with chronic NEP-I in contrast to markedly attenuated renal responses to exogenous ANF in untreated CHF. Despite enhanced ANF responsiveness and improved sodium balance in evolving CHF, a moderate degree of sodium retention was observed during chronic NEP-I in evolving CHF.ConclusionsEnzymatic degradation by neutral endopeptidase limits local renal responses to increases in endogenous and exogenous ANF in CHF independent of changes in systemic hemodynamics or augmented plasma concentrations of ANF. The moderate sodium retention observed during evolving CHF despite chronic NEP-I probably reflects the antinatriuretic effects of hemodynamic and humoral factors independent of ANF activity.

Background The NHLBI Percutaneous Transluminal Coronary Angioplasty (PTCA) Registry followed 1345 consecutive patients with first PTCA between 1977 and 1981 (registry 1) and 2136 consecutive patients with PTCA between 1985 and 1986 (registry 2). Changes in patient selection and in immediate and 1-year outcome are presented. This report extends to 5 years the comparison of the effects of early and more recent management with PTCA. Methods and Results Sixteen participating centers entered consecutive patients who had angioplasty for the first time between 1977 and 1981 and between 1985 and 1986. Patients with recent myocardial infarction (MI) were excluded. Vessel disease was defined according to the Coronary Artery Surgery Study. Successful dilatation required ≥20% reduction in luminal narrowing and <50% lumen diameter stenosis after intervention. Routine annual follow-up was conducted by telephone interview. The product-limit method was used to estimate freedom from untoward events, Cox regression analysis to model relative risk and adjusted relative risk of events between the two registries, and logistic regression when the exact time of outcome (such as recurrence of symptoms) was not known. Long-term event rates were computed by vessel disease for all patients and for the cohort of patients with initially successful PTCA. After adjustment for extent of disease, diabetes, prior bypass surgery (CABG), hypertension, age, and sex, the 5-year risk of death was similar in the two registry cohorts. However, rates of MI, CABG, and a combined outcome measure of death, MI, and/or CABG were significantly lower in the registry 2 cohort both for all patients and for patients who were initially treated successfully. Use of repeated PTCA was higher, and freedom from symptoms without adverse events was significantly better in the latter cohort. Conclusions Compared with registry 1, the management of the registry 2 cohort resulted in lower 5-year morbid event rates and reduced CABG operations. Mortality rates remained similar. When symptomatic status was considered in combination with events, a significantly better outcome was seen overall and in the initially successful cohort. In registry 2, repeated PTCA was used with much greater frequency early after the initial procedure.

Triamterene (2,4,7-triamino-6-phenylpteridine) was employed alone and in combination with hydrochlorothiazide in the treatment of patients with group 1 and 2 hypertension. In 21 patients, triamterene alone had an inconsistent antihypertensive effect on the systolic blood pressure, which was minimal in most patients. In 16 patients the combination of triamterene and hydrochlorothiazide (2:1 by weight) reduced the systolic blood pressure slightly more than did hydrochlorothiazide alone. Triamterene alone or in combination with hydrochlorothiazide produced an increase in the concentration of potassium in serum. Side effects due to triamterene were similar to those noted with thiazide diuretics. In addition, five patients had a decrease in blood hemoglobin concentration, and two patients had reversible alterations in liver function during triamterene therapy. Triamterene may be a useful adjunct for thiazidetreated hypertensive patients by decreasing the likelihood of complicating hypokalemia.

Nicotinic acid was administered orally to 33 patients with hypercholesterolemia in doses varying from 1.5 to 6.0 Gm. per day for periods of 3 months to 1½ years. Significant, sustained, and reproducible decreases in the concentration of cholesterol and total lipids in the plasma and of serum beta-lipoprotein cholesterol were observed in a majority of patients. This form of therapy appears to be effective, practical, and probably free from serious harmful effects.

BACKGROUND The purpose of this study was to estimate survival and quality of outcome and assess factors associated with outcome for patients out 5 to 15 years from their Fontan operation. METHODS AND RESULTS We studied 352 patients who had the Fontan operation prior to 1985. The overall 1-, 5-, and 10-year survival was 77%, 70%, and 60%, respectively. The following factors were significantly associated with lower survival: univentricular heart or complex congenital anomalies other than tricuspid atresia, early calendar year of operation, heterotaxia syndromes, early age at operation, increased pulmonary artery pressure, atrioventricular valve dysfunction, and higher (worse) New York Heart Association class. Reoperations were necessary for 103 of the 352 patients. At least 20% of the survivors have or have had cardiac arrhythmias requiring antiarrhythmic medication or mechanical pacemaker insertion. Between 7% and 10% of the patients have had or had protein-losing enteropathy/hypoproteinemia. At 5 years postoperatively, 122 patients (34.7%) were alive with a better New York Heart Association functional classification than preoperatively. Fifty-eight patients (16.5%) were alive and in the same functional classification, but 126 (35.8%) died within the first 5 years or were in a worse functional classification. Thirty-nine patients were doing excellently and 29 patients poorly 5 years after the operation. Of the surviving patients, 43% can do as much exercise as their peers, whereas 3% are incapable of exercise. CONCLUSIONS To assure good functional long-term outcome in addition to survival, clinicians must exclude from selection for Fontan operation patients known to be at high risk for death or poor outcome.