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A case of postpartum hypopituitarism (Sheehan's syndrome) associated with severe hyponatremia and congestive heart failure.

A case of a 69-year-old woman with postpartum hypopituitarism (Sheehan's syndrome) associated with congestive heart failure and severe hyponatremia is reported. She developed congestive heart failure after cholecystectomy, and marked improvement was noted by treatment with oxygen, digoxin, furosemide, and dopamine. Two weeks after surgery, she became confused, and hyponatremia, 106 mEq/l, was detected. She was referred to us. Past history revealed postpartum hemorrhage at the age of 34, followed by a failure to lactate, menoschesis, and loss of pubic hair and axillary hair. Hypertonic saline (1.5%) infusion and water restriction increased her serum sodium concentration into the low normal range. Despite hyponatremia, serum vasopressin was not suppressed. Basal levels of pituitary hormones were low, and they did not respond to provocation tests. Marked impairment of water excretion was noted, and plasma vasopressin was not suppressed during a water-loading test. These results suggest that inappropriately increased vasopressin played an important role in impaired water excretion, and this defect could have been responsible for the development of hyponatremia and congestive heart failure in this patient.

Aged↗

Effect of dexamethasone on the diurnal rhythm of plasma aldosterone in patients with congestive heart failure.

Diurnal rhythm studies were performed on 11 patients with congestive heart failure. Blood samples were taken for the determination of aldosterone, cortisol and plasma renin activity every 4 hours from 12:00 a.m. to 12:00 a.m. the following day. Following this control study, a second diurnal rhythm study was conducted under dexamethasone treatment (0.5 mg of dexamethasone every 4 hours for 48 hours). In the control study, aldosterone and cortisol fluctuated showing a diurnal rhythm with the lowest value in the evening and the highest value in the morning. Plasma renin activity rhythm was indistinct. Fluctuations in plasma renin activity were not parallel with aldosterone. Dexamethasone treatment suppressed cortisol to less than 1 microgram/100 ml. Aldosterone values decreased significantly in the morning (p less than 0.01); this was accompanied by the abolishment of aldosterone rhythm. Plasma renin activity rhythm remained indistinct following administration of dexamethasone. These results suggest that adrenocorticotrophic hormone plays an important role in the control of aldosterone diurnal rhythm in patients with congestive heart failure.

Adolescent↗

Skeletal muscle metabolism during exercise under ischemic conditions in congestive heart failure. Evidence for abnormalities unrelated to blood flow.

Previous studies with 31P nuclear magnetic resonance have demonstrated that patients with chronic congestive heart failure often exhibit increased glycolytic metabolism and impaired oxidative phosphorylation in exercising skeletal muscle, but the mechanism for these changes remains unresolved. This study was conducted to determine whether these abnormalities result from impaired blood flow or oxygen delivery. Nine patients with mild-to-moderate congestive heart failure and nine age- and size-matched, healthy control volunteers were studied during repetitive submaximal finger flexion exercise under aerobic and ischemic conditions. Skeletal muscle metabolism was assessed by 31P nuclear magnetic resonance of the flexor digitorum superficialis muscle. During steady-state aerobic exercise at 33% of each subject's predetermined maximum workload, the patients with congestive heart failure exhibited significantly lower pH values (6.65 +/- 0.22 vs. 6.97 +/- 0.09, p less than 0.002) and phosphocreatine concentrations, expressed as [phosphocreatine]/([phosphocreatine] + [inorganic phosphate]) (0.59 +/- 0.14 vs. 0.79 +/- 0.08, p less than 0.002). Similar differences were also present throughout ischemic exercise at the same workload. Based upon these measurements, calculated lactate production and adenosine 5'-triphosphate consumption rates were significantly higher in the patients with congestive heart failure. These results indicate that in many patients with congestive heart failure exercising muscle exhibits increased glycolytic metabolism and appears to be metabolically less efficient in relation to external work performed. These changes cannot be explained by impaired blood flow or oxygen delivery alone.

Adult↗

Clinical pharmacokinetics and therapeutic use of hydralazine in congestive heart failure.

Hydralazine (1-hydrazinophthalazine) has been used extensively in the treatment of hypertension and congestive heart failure and produces arteriolar vasodilation, in part, mediated by prostaglandins. Its associated reflex baroreceptor-mediated responses of tachycardia and increased ejection velocity are attenuated in congestive heart failure. A direct inotropic effect has been attributed to the drug. Pharmacokinetic data indicate hydralazine is absorbed well from the gastrointestinal tract, and has an extensive and complex metabolism depending on acetylator status: slow acetylators undergo primary oxidative metabolism, while rapid acetylators are acetylated. Half-lives, clearances and bioavailability of the drug are not significantly altered in congestive heart failure compared with hypertensive patients. A wide range of dosages in heart failure has been noted (150 to 3000 mg/24h), and may related to a saturation of the first-pass effect. Hydralazine improves haemodynamics in the short term in patients with increased peripheral vascular resistance, and has variable effects on pulmonary capillary wedge and left ventricular filling pressures. Prediction of the short term clinical response is difficult and appears to be independent of pharmacokinetics. A meta analysis did not demonstrate long term efficacy of hydralazine alone in heart failure, but combination therapy with nitrates has been shown to improve survival and exercise performance in patients with mild to moderate heart failure. Side effects are common and are dependent on dose, duration and acetylator status.

Heart Failure↗

Right ventricular-vascular interaction in congestive heart failure. Importance of low-frequency impedance.

BACKGROUND: Vasodilator agents are widely used in congestive heart failure. These agents may have important effects on the pulsatile aspects of right ventricular hydraulic load. METHODS AND RESULTS: Fifteen patients with severe congestive heart failure were studied during cardiac catheterization by use of high-fidelity pressure transducers and a catheter-mounted flow velocity probe. Three graded doses of nitroprusside were infused as pulmonary artery (PA) pressure and flow were continuously recorded. From Fourier transforms of signal-averaged waves, PA impedance, hydraulic power, and wave reflection indices were derived. At the highest dose of nitroprusside (66 +/- 41 micrograms/min), cardiac output was significantly improved, whereas PA mean and wedge pressure, resistance, impedance at the first harmonic, characteristic impedance, and wave reflection amplitude were all reduced. At the dose (32 +/- 20 micrograms/min) at which cardiac output first showed improvement, only PA mean pressure and first-harmonic impedance were significantly reduced. Hydraulic power cost per unit of forward flow was also lowered at this dose, despite lack of significant change in pulmonary vascular resistance. At the lowest dose of nitroprusside (11 +/- 4 micrograms/min), six patients experienced a decrease in stroke volume, whereas the other nine were either unchanged (n = 1) or showed an increase (n = 8). Multiple regression revealed that only the change in first-harmonic impedance correlated with this effect, increasing when stroke volume decreased and decreasing when stroke volume increased (P = .02). The change in first-harmonic impedance at this dose appeared to be caused by alterations in the amplitude of PA wave reflections. At higher doses, changes in mean PA pressure (but not in pulmonary vascular resistance) correlated with changes in stroke volume. CONCLUSIONS: Nitroprusside vasodilation at low doses alters PA hemodynamics in congestive heart failure primarily through changes in low-frequency impedance. In some patients, this effect is associated with decreased stroke output. At higher doses, favorable alterations in resistance, low- and high-frequency impedance, and wave reflections all contribute to increased forward flow and decreased power requirement per unit forward flow. These findings show that ventricular-vascular interaction is importantly affected by pulmonary vasodilation and that appreciation of pulsatile properties is required to understand the effects of pulmonary vasodilation on cardiac output.

Blood Flow Velocity↗

Economic outcomes of withdrawal of digoxin therapy in adult patients with stable congestive heart failure.

OBJECTIVES: This study sought to analyze the health and economic outcomes of withdrawal of digoxin therapy among U.S. adult patients with stable congestive heart failure. BACKGROUND: New information regarding the outcomes of digoxin withdrawal has been provided by the Prospective Randomized Study of Ventricular Failure and Efficacy of Digoxin (PROVED) and Randomized Assessment of Digoxin and Inhibitors of Angiotensin-Converting Enzyme (RADIANCE) trials. We interpreted and extrapolated the results of these trials to describe implications on a national level. METHODS: We used a decision-analytic model to estimate the outcomes of two alternative strategies to 1) continue and 2) withdraw digoxin in patients with congestive heart failure with normal sinus rhythm, New York Heart Association functional class II or III and left ventricular ejection fraction < or = 35%. Epidemiologic assumptions were derived from published reports and expert opinion. Assumptions regarding the effectiveness of digoxin therapy were derived from the RADIANCE and PROVED digoxin withdrawal trials. Hospital and Medicare data were used for economic assumptions. Calculated outcomes included treatment failures, cases of digoxin toxicity and health care costs. RESULTS: The continuation of digoxin therapy in these patients with congestive heart failure nationally would avoid an estimated 185,000 clinic visits, 27,000 emergency visits and 137,000 hospital admissions for congestive heart failure. After accounting for an estimated 12,500 cases of digoxin toxicity, the net annual savings would be $406 million, with a 90% range of uncertainty of $106 to $822 million. One-way sensitivity analysis indicated that digoxin therapy is cost-saving when the assumed annual incidence of digoxin toxicity is < or = 33%. CONCLUSIONS: The continuation of digoxin therapy in patients with stable congestive heart failure should be strongly considered, because this strategy is likely to lead to both lower costs and greater health benefits on the basis of available information.

Adult↗

Congestive heart failure as cause of fulminant hepatic failure.

In this patient with long-standing cardiomyopathy and congestive heart failure the syndrome of fulminant hepatic failure developed on two occasions; he recovered both times. There was no evidence of viral or toxic hepatitis as a cause of his liver failure. We conclude that in this case, aggravation of long-standing congestive heart failure may have led to severe hepatocellular necrosis with signs of encephalopathy not commonly observed.

Acute Disease↗

A double-blind, cross-over comparison of the effects of a loop diuretic and a dopamine receptor agonist as first line therapy in patients with mild congestive heart failure.

We compared the effects of the orally active dopamine agonist ibopamine with the loop diuretic frusemide as first-line therapy in patients with mild congestive heart failure. Fourteen patients with New York Heart Association class II congestive heart failure were enrolled in a double-blind, cross-over study. After baseline measurements of clinical and symptomatic status, modified Bruce exercise time, high-level exercise time, corridor walk time, regional blood flow, pedometer scores, 24 h urine volume and sodium excretion and neurohumoural factors, patients were randomly allocated to receive either frusemide 40 mg o.d. or ibopamine 100 mg t.d.s. for 8 weeks. Assessments were performed at 2 weekly intervals. After 8 weeks, patients crossed over into the alternate treatment arm for a further 8 weeks, with further assessments performed every 2 weeks. There were four exacerbations of heart failure during ibopamine treatment and none during frusemide treatment. After 8 weeks of treatment, modified Bruce exercise time was 901 +/- 73 s with frusemide and 646 +/- 134 s with ibopamine (P < 0.05). Twenty-four hour urinary sodium excretion at weeks 2 and 4 (P < 0.05), and 24 h urinary volume at week 2 (P = 0.0001) were lower during ibopamine treatment. At week 8, supine (P = 0.076) and erect renin (P = 0.05) were lower with ibopamine treatment. In conclusion, ibopamine is ineffective as first line therapy for congestive heart failure, probably because of a lesser diuretic potency than frusemide.

Adult↗

Hemodynamic results of perorally administered converting enzyme inhibitors in congestive heart failure.

The acute hemodynamic response to captopril (8 patients) and enalapril (8 patients) was evaluated in congestive heart failure patients in NYHA functional class III. All patients had a history of congestive heart failure for more than six months. The results show marked interindividual variations but average values for cardiac output increase and decrease in filling pressures agree with findings in the literature. 6 patients in the captopril group and five in the enalapril group were started on maintenance therapy. One patient in the captopril group deteriorated and underwent a successful heart transplantation and one patient in the enalapril group returned with arrhythmias and hypertension (probably not drug-related) after 48 h of therapy. Our data indicate that activation of the renin-angiotensin system through excessive administration of loop-diuretics is associated with a risk of hypovolemia and thus drug-induced hypotension that deserves special attention when considering converting enzyme inhibitor therapy in congestive heart failure.

Administration, Oral↗

Breathing pattern abnormalities and arterial oxygen desaturation during sleep in the congestive heart failure syndrome. Improvement following medical therapy.

We observed breathing pattern abnormalities and arterial oxygen desaturation in patients with stable congestive heart failure during overnight polysomnography. To determine whether congestive heart failure was the reason for these abnormalities, we then studied six additional patients before and after treatment of heart failure. Breathing was more abnormal (153 +/- 87 episodes/night) during decompensation of heart failure and improved with medical therapy (72 +/- 100 episodes/night) (p less than 0.05). Abnormal breathing patterns resolved in three patients, improved in two, and were unchanged in one patient after therapy. Allographic cardiac transplantation in one patient whose sleep study remained unchanged after medical therapy was associated with resolution of breathing pattern abnormalities and severe desaturation during sleep. Therapy-related improvement in nocturnal respiratory events suggests congestive heart failure is a contributing factor for breathing abnormalities and arterial oxygen desaturation during sleep.

Aged↗

Influence of age on the prognostic importance of left ventricular dysfunction and congestive heart failure on long-term survival after acute myocardial infarction. TRACE Study Group.

The aim of this study was to assess the importance of congestive heart failure and left ventricular (LV) systolic dysfunction after an acute myocardial infarction (AIM) on long-term mortality in different age groups. A total of 7,001 consecutive enzyme-confirmed AMIs (6,676 patients) were screened for entry into the TRAndolapril Cardiac Evaluation (TRACE) study. Medical history, echocardiographic estimation of LV systolic function determined as wall motion index, infarct complications, and survival were documented for all patients. To study the importance of congestive heart failure and wall motion index independent of age, we performed Cox proportional-hazard models in 4 different age strata (< or = 55 years, 56 to 65 years, 66 to 75 years, and > 75 years). Patients in these strata had 1-year mortality rates of 5%, 11%, 21%, and 32%, respectively. Three-year mortality rates were 11%, 20%, 34%, and 55%, respectively. The risk ratios (and 95% confidence limits) associated with congestive heart failure in the same 4 age strata were 1.9 (1.3 to 2.9), 2.8 (2.1 to 3.7), 1.8 (1.5 to 2.2) and 1.8 (1.5 to 2.2), respectively. The risk ratios associated with decreasing wall motion index were 6.5 (3.6 to 11.4), 3.3 (2.3 to 4.6), 2.7 (2.2 to 3.4), and 2.1 (1.7 to 2.6), respectively. In absolute percentages, there was an excess 3-year mortality associated with congestive heart failure in the 4 age strata of 14%, 24%, 25%, and 28% respectively. The absolute excess in 3-year mortality associated with LV systolic dysfunction in the 4 age strata was 15%, 19%, 25%, and 21%, respectively. Thus, the relative importance of LV systolic dysfunction and congestive heart failure diminished with increasing age. However, the absolute excess mortality associated with congestive heart failure and LV systolic dysfunction was more pronounced in the elderly than in the young.

Age Factors↗

Circulating levels of cytokines and their endogenous modulators in patients with mild to severe congestive heart failure due to coronary artery disease or hypertension.

OBJECTIVES: This study sought to determine the circulating levels of cytokines and their respective endogenous modulators in patients with congestive heart failure of variable severity. BACKGROUND: Activation of immune elements localized in the heart or periphery, or both, may promote release of cytokines in patients with congestive heart failure. Although an increased circulating level of tumor necrosis factor-alpha (TNF-alpha) and its soluble receptor type II (sTNF-RII) is well documented, less is known about other cytokines (i.e., interleukin-1-beta [IL-1-beta], interleukin-6 [IL-6] and interleukin-2 [IL-2] and their soluble receptor/receptor antagonists). METHODS: Circulating levels of TNF-alpha and sTNF-RII, IL-1-beta, IL-1 receptor antagonist (IL-1-Ra), IL-6, IL-6 soluble receptor (IL-6-sR), IL-2 and IL-2 soluble receptor-alpha were measured using enzyme-linked immunosorbent assay kits (Quantikine, R&D Systems) in 80 patients with congestive heart failure due to coronary artery disease or hypertension. The severity of their symptoms, which ranged from New York Heart Association functional class I to IV, was confirmed by measurement of peak oxygen consumption. RESULTS: The percentage of patients with elevated levels of cytokines and their corresponding soluble receptor/receptor antagonists significantly increased with functional class. For TNF-alpha and IL-1-beta, the percentage of patients with elevated levels of soluble receptor/receptor antagonists was higher than that of patients with elevated levels of the cytokine itself. For IL-6, the percentage of patients with elevated levels of IL-6-sR tended to be lower than that of patients with elevated levels of IL-6. All but two patients had undetectable levels of IL-2, and all but seven had levels of IL-2-sR within a normal range. CONCLUSIONS: In patients with congestive heart failure, circulating levels of cytokines increased with the severity of symptoms. In these patients, circulating levels of sTNF-RII and IL-1-Ra are more sensitive markers of immune activation than are circulating levels of TNF-alpha and IL-1-beta, respectively. Levels of IL-2 and IL-2-sR are not elevated when congestive heart failure is due to coronary artery disease or hypertension.

Aged↗

Serum magnesium aberrations in furosemide (frusemide) treated patients with congestive heart failure: pathophysiological correlates and prognostic evaluation.

OBJECTIVES: To determine the prevalence of hypomagnesaemia and hypermagnesaemia, to discern various factors associated with abnormal serum magnesium, and to estimate prognostic significance of serum magnesium aberrations in patients with congestive heart failure. DESIGN: Observational study. SETTING: Medical department of a university hospital (tertiary referral centre). PATIENTS: 404 consecutive patients admitted with congestive heart failure as one of the diagnoses and previously treated with furosemide (frusemide) for at least three months. MAIN OUTCOME MEASURES: Clinical, biochemical, and electrocardiographic variables were analysed with respect to serum magnesium aberrations. Following discharge, mortality rates, including sudden death, were registered. RESULTS: Hypomagnesaemia was found in 50 patients (12.3%) and 20 (4.9%) were hypermagnesaemic. Female sex (p < 0.04), diabetes mellitus (p < 0.006), hypocalcaemia (p = 0.03), hyponatraemia (p < 0.05), malignant disease (p = 0.05), and high fever (p = 0.05) were statistically associated with hypomagnesaemia. Renal failure, severe congestive heart failure, and high dose furosemide treatment (> 80 mg/day) were associated with hypermagnesaemia (p < 0.001, p = 0.05, and p < 0.03, respectively). Hypermagnesaemic patients were older and weighed less. On follow up (median duration 43 months), 169 (41.8%) died, with 22 (13%) sudden deaths. Mortality was highest with hypermagnesaemia, lowest with normomagnesaemia, and intermediate with hypomagnesaemia. After adjustment for renal failure, old age, and severity of congestive heart failure, hypomagnesaemia but not hypermagnesaemia emerged as being significantly associated with shorter survival (p = 0.009). No statistical association was found between sudden death and magnesium concentrations. CONCLUSIONS: While hypermagnesaemia seems to represent a prognostic marker only, hypomagnesaemia appears to have an adverse pathophysiological effect. The subgroup of patients at risk for hypomagnesaemia requires frequent serum magnesium determinations and magnesium replacement for as long as hypomagnesaemia persists.

Aged↗

Value of New York Heart Association classification, radionuclide ventriculography, and cardiopulmonary exercise tests for selection of patients for congestive heart failure studies.

To evaluate the necessity of an objective cardiopulmonary exercise test in the selection procedure of patients for heart failure studies, 50 patients with congestive heart failure New York Heart Association (NYHA) class II and III and a left ventricular ejection fraction less than 40% were subjected to a cardiopulmonary exercise test. The results of the exercise test were compared with the independent clinical estimation of NYHA class and data of measurements obtained at rest. The NYHA classification separated the patients with a mild to moderate impairment of aerobic capacity from patients with a moderate to severe impairment of aerobic capacity very well, but 32% of the NYHA class II patients had a near normal aerobic capacity, and 29% of the NYHA class III patients had a very severe impairment of aerobic capacity, more compatible with NYHA class IV. Only data from exercise measurements showed differences between groups. The determination of maximal aerobic capacity for an objective assessment of patients' performance at exercise is necessary for a proper selection procedure of patients for heart failure studies.

Adult↗

Iodine-123 metaiodobenzylguanidine images reflect intense myocardial adrenergic nervous activity in congestive heart failure independent of underlying cause.

OBJECTIVES: This study was undertaken to assess myocardial adrenergic activity using iodine-123 metaiodobenzylguanidine (MIBG) imaging in patients with heart failure. BACKGROUND: In patients with congestive heart failure, adrenergic nerve activity is accelerated. However, whether myocardial adrenergic nerve activity reflects the severity of heart failure and its relation to the underlying cause have not yet been elucidated. METHODS: Planar MIBG images were obtained from 96 patients with heart failure and compared with images from 9 age-matched healthy subjects. Groups 1 and 2 included 65 patients with heart failure related to impaired myocardial function and whose left ventricular ejection fraction was < 40% (group 1 = 40 patients with dilated cardiomyopathy; group 2 = 25 patients with ischemic cardiomyopathy). Group 3 included 31 patients with heart failure related to a mechanical abnormality and whose left ventricular ejection fraction was > 40% (mitral regurgitation in 16, aortic regurgitation in 9, aortic and mitral regurgitation in 4, ruptured aneurysm of Valsalva in 2). Myocardial uptake of MIBG was calculated as the heart/mediastinal activity ratio. Storage and release of MIBG were calculated as percent myocardial MIBG washout from 15 min to 4 h after isotope injection. RESULTS: The heart/mediastinal activity ratio in the immediate images (15 min) showed a significant decrease only in patients with severe heart failure (groups 1 and 2). The myocardial washout was accelerated in all three heart failure groups. The level of myocardial washout was related to severity of heart failure and correlated well with New York Heart Association functional classification. CONCLUSIONS: In severe heart failure associated with cardiomyopathy, norepinephrine uptake is reduced. In addition, myocardial adrenergic nerve activity is accelerated in proportion to severity of heart failure, independent of the underlying cause.

3-Iodobenzylguanidine↗

[Significance of electrocardiographic QRS width in patients with congestive heart failure: a marker for biventricular pacing].

OBJECTIVES: Biventricular pacing may be valuable for the treatment of patients with intractable heart failure, but how many patients in Japan would benefit from this type of therapy remains uncertain. This study investigated the incidence of intraventricular conduction delay in the electrocardiogram(ECG) as a marker of the need for biventricular pacing, as well as the underlying etiology of heart failure in patients admitted with congestive heart failure. METHODS: Patients with heart failure admitted to the Tokai University Hospital from January 1990 to September 2000 were studied retrospectively. The distribution of age, sex and underlying diseases, and that of the rhythm and the QRS width in ECG recordings were analyzed. Patients with a QRS width of over 121 msec in the ECG were classified as the 'wide QRS' group. RESULTS: Of a series of 1,200 consecutive patients with heart failure, 872 patients, 499 males and 373 females (mean age 67.9 +/- 13.9 years) were admitted to the hospital and 71 had 'wide QRS' by ECG. Among those in the 'wide QRS' group, 37% had ischemic heart disease and 14% had dilated cardiomyopathy. The widest QRS complexes were encountered in patients with dilated cardiomyopathy and the largest number of wide QRS complexes was encountered in patients with ischemic heart disease. CONCLUSIONS: The most frequent causes of heart failure among patients considered suitable for biventricular pacing were ischemic heart disease and dilated cardiomyopathy, which is consistent with previous reports. Compared with the statistics reported from western countries, the incidence of ischemic heart disease and the incidence of intraventricular conduction delay were lower in Japanese patients with heart failure. The incidence of intraventricular conduction delay among patients with heart failure was 8.6%. Therefore, fewer patients need biventricular pacing in Japan than in western countries. Nevertheless, patients with heart failure resistant to other therapies might still benefit from this type of therapy.

Adult↗

Comparison of intravenous piretanide and furosemide in patients with congestive heart failure.

In order to compare the efficacy of piretanide, a loop diuretic, with furosemide in the setting of congestive heart failure, 20 patients with moderate-to-severe congestive heart failure were studied in a double-blind fashion. Ten patients received piretanide and 10 furosemide intravenously every 12 h for 3 days. Prior to treatment, the groups were indistinguishable in all relevant clinical characteristics. No major adverse reactions were encountered in either patient group. There was no ototoxicity, worsening of cardiac arrhythmias, worsening of diabetes, or systematic perturbation of the serum digoxin concentration. Patients in both groups had similar mild elevation in BUN and serum uric acid levels at the end of the study. There was an equal weight loss for patients in the two groups and an equal excretion of Na, K, and total volume of urine for the two groups. The urinary Na/K ratio was also indistinguishable between the two groups. In both groups, plasma aldosterone concentration tended to increase; there was no alteration in plasma renin activity. We conclude that piretanide and furosemide are equieffective for treatment of congestive heart failure in the doses used. Although in some settings piretanide is potassium sparing, we were not able to demonstrate this property in the population studied.

Adult↗

Theophylline disposition in Korean patients with congestive heart failure.

OBJECTIVE: This study proposed to determine the systemic disposition of theophylline in Korean adult patients during decompensated congestive heart failure compared with disposition after recovery. DESIGN: An experimental, prospective, self-controlled, nonrandomized design was used. SETTING: The study was performed in a general community hospital located in Pusan, Korea. PATIENTS: Eight nonsmoking elderly Korean patients with decompensated congestive heart failure presenting to the emergency department were included in the study. Consecutive patients who met entrance criteria were selected. All patients completed the study. INTERVENTIONS: A single dose of aminophylline 6 mg/kg was administered by intravenous infusion over 30 minutes. Standard methods of congestive heart failure therapy were used in each patient, including bed rest, restriction of sodium, and drug therapy including digoxin. After compensation of congestive heart failure was achieved, the theophylline infusion was repeated. OUTCOME MEASURES: Serum theophylline concentrations were measured at 2, 6, 12, and 18 hours after completion of the dose at baseline and following treatment. RESULTS: A clinically and statistically significant improvement in mean theophylline total body clearance was demonstrated following treatment (from 21.7 +/- 2.8 to 43.4 +/- 4.7 mL/kg/h [mean +/- SEM]; p < 0.01). Comparison of these results with a computer model based on literature averages of peoples of all nationalities showed significant underprediction of theophylline clearance both before (p < 0.05) and after (p < 0.01) treatment. The theophylline elimination half-life prior to treatment was 18.2 +/- 2.2 hours and decreased to 9.1 +/- 0.8 hours following treatment (p < 0.01). There was no statistical difference between the computer-model predicted initial theophylline half-life and the measured value, but the model significantly underpredicted the improvement following treatment. CONCLUSIONS: The improvement in theophylline clearance demonstrated in this study appears to be greater than that reported for Western patients. This has practical application to the calculation of appropriate theophylline maintenance dosage regimens in Korean patients with cardiac failure. These data support the need for consideration of racial differences in individualizing dosage regimens. We suggest that all kinetic models, whether software supported or not, should consider incorporating ethnic origin as a demographic factor that helps select the proper model for individual patients.

Aged↗