MEDLINE Abstracts: Diuretics and Congestive Heart Failure
Hardig L, Daae C, Dellborg M, Kontny F, et al
J Intern Med. 2000 May;247(5):597-600
Objectives: To measure the concentrations of thiamine and thiamine esters by high-pressure liquid chromatography (HPLC) in elderly patients treated with furosemide for heart failure and in a control group. DESIGN: A cross-sectional study of blood thiamine and thiamine ester concentrations.
Subjects: Forty-one patients admitted to hospital for heart failure and 34 elderly living at home. No vitamin supplementation was allowed.
Results: Compared with the healthy controls, furosemide-treated patients had significantly reduced whole blood thiamine phosphate (TP; 4.4 +/- 2.2 vs. 7.6 +/- 2.0 nmol L-1) and thiamine diphosphate (TPP; 76 +/- 21.5 vs. 91 +/- 19.8 nmol L-1) (mean +/- SD). When the thiamine concentrations were related to the haemoglobin concentrations, which were reduced in the heart failure patients, the levels of TP (nmol g-1 Hb) were 0.38 +/- 0.26 vs. 0.54 +/- 0.17 (P < 0.0001), and of TPP were 6.35 +/- 1.76 vs. 6.37 +/- 1.29 (P = 0.95). There were no differences in T and TP concentrations in plasma between the two groups.
Conclusions: The elderly patients with heart failure treated with furosemide have not reduced the storage form of thiamine, TPP, but only TP. This change is most likely not an expression of a thiamine deficiency, but rather of an altered metabolism of thiamine, which is not understood at present.
van Kraaij DJ, Jansen RW, Gribnau FW, et al
Drugs Aging. 2000 Apr;16(4):289-300
Long term prescription of diuretics for heart failure is very prevalent among elderly patients, although the rationale for such a treatment strategy is often unclear, as diuretics are not indicated if volume overload is absent. The concept of diastolic heart failure in the elderly might particularly change the role of diuretic therapy, since diuretics may have additional adverse effects in these patients. This paper reviews the effects of diuretic therapy in elderly patients with heart failure, emphasising the differences between patients with normal and decreased left ventricular systolic function. Studies on diuretic withdrawal in elderly patients with heart failure are discussed, with emphasis on issues involved in decision making such as diuretic dose reduction and withdrawal in elderly patients and factors that have been established to predict successful withdrawal. Existing guidelines on the prescription of diuretics in elderly patients with heart failure with normal and decreased left ventricular systolic function and in those with diastolic heart failure are also discussed. By reducing intravascular volume, diuretics may further impair ventricular diastolic filling in patients with diastolic heart failure and thus reduce stroke volume. Indeed, preliminary studies demonstrate that diuretics may provoke or aggravate hypotension on standing and after meals in these patients. Therefore, it is suggested that elderly patients with heart failure with intact left ventricular systolic function should not receive long term diuretic therapy, unless proven necessary to treat or prevent congestive heart failure. This implies that physicians should carefully evaluate the opportunities for diuretic dose tapering or withdrawal in all of these patients, and that a cautiously guided intermittent diuretic treatment modality may be critical in the care for older patients with heart failure with intact left ventricular systolic function.
Gottlieb SS, Skettino SL, Wolff A, et al
J Am Coll Cardiol. 2000 Jan;35(1):56-9
Objectives: To determine the effects of furosemide and the selective A1 adenosine receptor BG9719 on renal function in patients with congestive heart failure (CHF).
Background: Studies suggest that adenosine may affect renal function by various mechanisms, but the effects of blockade of this system in humans is unknown. In addition, the effects of a therapeutic dose of furosemide on glomerular filtration rate (GFR) and renal plasma flow (RPF) in heart failure patients are controversial.
Methods: On different days, 12 patients received placebo, BG9719 and furosemide. Glomerular filtration rate, RPF and sodium and water excretion were assessed immediately following drug administration.
Results: Glomerular filtration rate was 84 +/- 23 ml/min/1.73m2 after receiving placebo, 82 +/- 24 following BG9719 administration and a decreased (p < 0.005) 63 +/- 18 following furosemide. Renal plasma flow was unchanged at 293 +/- 124 ml/min/1.73m2 on placebo, 334 +/- 155 after receiving BG9719 and 374 +/- 231 after receiving furosemide. Sodium excretion increased from 8 +/- 8 mEq following placebo administration to 37 +/- 26 mEq following BG9719 administration. In the six patients in whom it was measured, sodium excretion was 104 +/- 78 mEq following furosemide administration.
Conclusions: Natriuresis is effectively induced by both furosemide and the adenosine A1 antagonist BG9719 in patients with CHF. Doses of the two drugs used in this study did not cause equivalent sodium and water excretion but only furosemide decreased GFR. These data suggest that adenosine is an important determinant of renal function in patients with heart failure.
Struthers AD, Anderson G, Donnan PT, et al
Heart. 2000 Jan;83(1):12-6
Objective: To examine whether social deprivation has any independent effect on emergency cardiac hospitalisations in patients with chronic heart failure (CHF). DESIGN: Cohort study of 478 patients with CHF who had been hospitalised before 1993 and who were followed up during 1993 and 1994.
Setting: Emergency admissions within Tayside acute hospitals.
Patients: 478 CHF patients who had a previous myocardial infarction, a previous CHF admission, and were on diuretic treatment.
Main Outcome Measures: Emergency hospital admissions are divided into those for all causes and those for cardiac causes only.
Results: Social deprivation was significantly associated with an increase in the number of cardiac hospitalisations (p = 0.007). This effect was mainly caused by increasing the proportion of patients hospitalised in each deprivation category (26% in deprivation category 1-2 versus 40% in deprivation category 5-6, p = 0.03). This effect of deprivation was independent of disease severity, as judged by the dose of prescribed diuretic, the death rate, and the duration of each hospital stay. Non-adherence with diuretic treatment could not account for these findings either.
Conclusions: Social deprivation increases the chance of a CHF patient being rehospitalised independently of disease severity. Possible explanations are that doctors who look after socially deprived patients have a lower threshold for cardiac hospitalisation of their patients, or that social deprivation alters the way a CHF patient accesses medical care during decompensation. Understanding how social deprivation influences both doctor and patient behaviour in the prehospital phase is now crucial in order to reduce the amplifying effect that social deprivation appears to have on cardiac hospitalisations.
Harjai KJ, Dinshaw HK, Nunez E, et al
Int J Cardiol. 1999 Dec 1;71(3):219-25
In 111 patients with left ventricular ejection fraction < or =30% who required hospitalization for heart failure, we examined the association between outpatient dose of diuretic agents and all-cause mortality. In comparison to patients who were not on treatment with diuretics prior to hospitalization, patients being treated with 'low' doses of diuretics (<80 mg/day of furosemide) and those being treated with 'high' doses of diuretics (> or =80 mg/day of furosemide) were more likely to die during follow-up after adjustment for other clinical parameters (adjusted relative risks, RR, 3.1 and 4.6).
Constant J
Cardiology .1999;92(3):156-61
The main purpose of using diuretics is usually lost sight of, i.e. it is for the relief of dyspnea by using the least amount of a diuretic. The production of a low output state and hypercoagulation in an attempt to achieve dry weight by lowering blood volume excessively are among the hazards of using more diuretic than is absolutely necessary to achieve the goal of relieving dyspnea. The use of jugular venous pressure measurement and the status of dyspnea should have precedence over body weight in determining diuretic dose adjustment. Often forgotten in using diuretics is that potassium without magnesium will not enter cells and that the almost universal preference for furosemide over thiazides threatens to increase the incidence of osteoporosis. Also, the tendency to ignore loss of the water-soluble vitamins thiamine and ascorbic acid may result in refractory edema and the inability to manage the stresses of congestive heart failure.
Tomiyama H, Nakayama T, Watanabe G, et al
Am Heart J. 1999 Mar;137(3):543-8
Background: We investigated the effects of a short-acting loop diuretic (furosemide) and a long-acting loop diuretic (azosemide) on heart rate variability, fluid balance, and neurohormonal responses in patients with mild to moderate chronic congestive heart failure.
Methods: Nineteen patients with mild to moderate chronic congestive heart failure received furosemide (40 to 60 mg/day) or azosemide (60 to 90 mg/day) for 5 days in a crossover manner. We performed time-domain and frequency-domain analyses of 24-hour Holter electrocardiographic recordings to assess heart rate variability.
Results: The 24-hour urinary sodium excretion was similar during the furosemide and azosemide treatment periods but was significantly greater in the first 2 hours after drug administration during furosemide treatment. Plasma renin activity and the hematocrit level increased and high-frequency power significantly decreased 2 hours after the administration of furosemide only. The standard deviation of all normal R-R intervals and the root mean square of successive differences in the R-R interval were lower with furosemide than with azosemide (P <.05).
Conclusions: Furosemide, a short-acting loop diuretic, has a greater influence on heart rate variability and fluid balance than azosemide, a long-acting loop diuretic, in patients with mild to moderate chronic congestive heart failure.
Saarela T, Lanning P, Koivisto M, et al
Eur J Pediatr. 1999 Aug;158(8):668-72
In order to study the incidence and course of nephrocalcinosis in full-term infants with congestive heart failure receiving long-term furosemide treatment, 36 such infants (median age 2.9 months, range 1.2-8.0) and 36 full-term control infants not receiving any diuretics (median age 3.4 months, range 1.1-8.4) were studied by renal ultrasonography and random urine calcium variables. The infants with nephrocalcinosis were followed at 3-6 month intervals up to 2 years of age, or until ultrasonic resolution. Nephrocalcinosis was found in 5 out of the 36 (14%) treated infants, but in none of the controls (P = 0.03). The dose of furosemide was higher in the infants with nephrocalcinosis than in those without (1.9+/-0.6 vs. 1.3+/-0.4 mg/kg per day; P = 0.01). The urinary calcium concentration was higher in the infants receiving furosemide than in controls and a similar trend was observed in the urinary calcium/creatinine ratio, but these variables did not differ between the study infants with and without nephrocalcinosis. Ultrasonic resolution of nephrocalcinosis was observed in 3 of the 5 infants at 12 months, but in the other 2 the condition still persisted at 24 months. CONCLUSIONS: Long-term furosemide treatment in full-term infants with congestive heart failure entails a considerable risk of developing nephrocalcinosis. Renal ultrasonography is warranted in these patients within a few months after initiation of the treatment and in the case of nephrocalcinosis alteration of the diuretic regimen is to be considered.
Kramer BK, Schweda F, Riegger GA
Am J Med. 1999 Jan;106(1):90-6
Diuretic therapy decreases capillary wedge pressure and improves New York Heart Association (NYHA) functional class both in acute and chronic heart failure. In advanced symptomatic heart failure, loop diuretics are generally necessary to improve symptoms of congestion. Diuretic resistance in the edematous patient has been defined as a clinical state in which diuretic response is diminished or lost before the therapeutic goal of relief from edema has been reached. The major causes of diuretic resistance are functional renal failure (prerenal azotemia), hyponatremia, altered diuretic pharmacokinetics, and sodium retention caused by counterregulatory mechanisms intended to reestablish the effective arterial blood volume. Therapeutic approaches to combat diuretic resistance include restriction of fluid and sodium intake, use of angiotensin-converting-enzyme (ACE) inhibitors, changes in route (oral, intravenous) and timing (single dose, multiple doses, continuous infusion) of diuretic therapy, and use of diuretic combinations.
MEDLINE Abstracts: Diuretics and Congestive Heart Failure
Reduced Thiamine Phosphate, But Not Thiamine Diphosphate, in Erythrocytes in Elderly Patients With Congestive Heart Failure Treated With Furosemide
Hardig L, Daae C, Dellborg M, Kontny F, et al
J Intern Med. 2000 May;247(5):597-600
Objectives: To measure the concentrations of thiamine and thiamine esters by high-pressure liquid chromatography (HPLC) in elderly patients treated with furosemide for heart failure and in a control group. DESIGN: A cross-sectional study of blood thiamine and thiamine ester concentrations.
Subjects: Forty-one patients admitted to hospital for heart failure and 34 elderly living at home. No vitamin supplementation was allowed.
Results: Compared with the healthy controls, furosemide-treated patients had significantly reduced whole blood thiamine phosphate (TP; 4.4 +/- 2.2 vs. 7.6 +/- 2.0 nmol L-1) and thiamine diphosphate (TPP; 76 +/- 21.5 vs. 91 +/- 19.8 nmol L-1) (mean +/- SD). When the thiamine concentrations were related to the haemoglobin concentrations, which were reduced in the heart failure patients, the levels of TP (nmol g-1 Hb) were 0.38 +/- 0.26 vs. 0.54 +/- 0.17 (P < 0.0001), and of TPP were 6.35 +/- 1.76 vs. 6.37 +/- 1.29 (P = 0.95). There were no differences in T and TP concentrations in plasma between the two groups.
Conclusions: The elderly patients with heart failure treated with furosemide have not reduced the storage form of thiamine, TPP, but only TP. This change is most likely not an expression of a thiamine deficiency, but rather of an altered metabolism of thiamine, which is not understood at present.
Diuretic Therapy in Elderly Heart Failure Patients With and Without Left Ventricular Systolic Dysfunction
van Kraaij DJ, Jansen RW, Gribnau FW, et al
Drugs Aging. 2000 Apr;16(4):289-300
Long term prescription of diuretics for heart failure is very prevalent among elderly patients, although the rationale for such a treatment strategy is often unclear, as diuretics are not indicated if volume overload is absent. The concept of diastolic heart failure in the elderly might particularly change the role of diuretic therapy, since diuretics may have additional adverse effects in these patients. This paper reviews the effects of diuretic therapy in elderly patients with heart failure, emphasising the differences between patients with normal and decreased left ventricular systolic function. Studies on diuretic withdrawal in elderly patients with heart failure are discussed, with emphasis on issues involved in decision making such as diuretic dose reduction and withdrawal in elderly patients and factors that have been established to predict successful withdrawal. Existing guidelines on the prescription of diuretics in elderly patients with heart failure with normal and decreased left ventricular systolic function and in those with diastolic heart failure are also discussed. By reducing intravascular volume, diuretics may further impair ventricular diastolic filling in patients with diastolic heart failure and thus reduce stroke volume. Indeed, preliminary studies demonstrate that diuretics may provoke or aggravate hypotension on standing and after meals in these patients. Therefore, it is suggested that elderly patients with heart failure with intact left ventricular systolic function should not receive long term diuretic therapy, unless proven necessary to treat or prevent congestive heart failure. This implies that physicians should carefully evaluate the opportunities for diuretic dose tapering or withdrawal in all of these patients, and that a cautiously guided intermittent diuretic treatment modality may be critical in the care for older patients with heart failure with intact left ventricular systolic function.
Effects Of BG9719 (CVT-124), an A1-Adenosine Receptor Antagonist, and Furosemide on Glomerular Filtration Rate and Natriuresis in Patients With Congestive Heart Failure
Gottlieb SS, Skettino SL, Wolff A, et al
J Am Coll Cardiol. 2000 Jan;35(1):56-9
Objectives: To determine the effects of furosemide and the selective A1 adenosine receptor BG9719 on renal function in patients with congestive heart failure (CHF).
Background: Studies suggest that adenosine may affect renal function by various mechanisms, but the effects of blockade of this system in humans is unknown. In addition, the effects of a therapeutic dose of furosemide on glomerular filtration rate (GFR) and renal plasma flow (RPF) in heart failure patients are controversial.
Methods: On different days, 12 patients received placebo, BG9719 and furosemide. Glomerular filtration rate, RPF and sodium and water excretion were assessed immediately following drug administration.
Results: Glomerular filtration rate was 84 +/- 23 ml/min/1.73m2 after receiving placebo, 82 +/- 24 following BG9719 administration and a decreased (p < 0.005) 63 +/- 18 following furosemide. Renal plasma flow was unchanged at 293 +/- 124 ml/min/1.73m2 on placebo, 334 +/- 155 after receiving BG9719 and 374 +/- 231 after receiving furosemide. Sodium excretion increased from 8 +/- 8 mEq following placebo administration to 37 +/- 26 mEq following BG9719 administration. In the six patients in whom it was measured, sodium excretion was 104 +/- 78 mEq following furosemide administration.
Conclusions: Natriuresis is effectively induced by both furosemide and the adenosine A1 antagonist BG9719 in patients with CHF. Doses of the two drugs used in this study did not cause equivalent sodium and water excretion but only furosemide decreased GFR. These data suggest that adenosine is an important determinant of renal function in patients with heart failure.
Social Deprivation Increases Cardiac Hospitalisations in Chronic Heart Failure Independent of Disease Severity and Diuretic Non-Adherence
Struthers AD, Anderson G, Donnan PT, et al
Heart. 2000 Jan;83(1):12-6
Objective: To examine whether social deprivation has any independent effect on emergency cardiac hospitalisations in patients with chronic heart failure (CHF). DESIGN: Cohort study of 478 patients with CHF who had been hospitalised before 1993 and who were followed up during 1993 and 1994.
Setting: Emergency admissions within Tayside acute hospitals.
Patients: 478 CHF patients who had a previous myocardial infarction, a previous CHF admission, and were on diuretic treatment.
Main Outcome Measures: Emergency hospital admissions are divided into those for all causes and those for cardiac causes only.
Results: Social deprivation was significantly associated with an increase in the number of cardiac hospitalisations (p = 0.007). This effect was mainly caused by increasing the proportion of patients hospitalised in each deprivation category (26% in deprivation category 1-2 versus 40% in deprivation category 5-6, p = 0.03). This effect of deprivation was independent of disease severity, as judged by the dose of prescribed diuretic, the death rate, and the duration of each hospital stay. Non-adherence with diuretic treatment could not account for these findings either.
Conclusions: Social deprivation increases the chance of a CHF patient being rehospitalised independently of disease severity. Possible explanations are that doctors who look after socially deprived patients have a lower threshold for cardiac hospitalisation of their patients, or that social deprivation alters the way a CHF patient accesses medical care during decompensation. Understanding how social deprivation influences both doctor and patient behaviour in the prehospital phase is now crucial in order to reduce the amplifying effect that social deprivation appears to have on cardiac hospitalisations.
The Prognostic Implications of Outpatient Diuretic Dose in Heart Failure
Harjai KJ, Dinshaw HK, Nunez E, et al
Int J Cardiol. 1999 Dec 1;71(3):219-25
In 111 patients with left ventricular ejection fraction < or =30% who required hospitalization for heart failure, we examined the association between outpatient dose of diuretic agents and all-cause mortality. In comparison to patients who were not on treatment with diuretics prior to hospitalization, patients being treated with 'low' doses of diuretics (<80 mg/day of furosemide) and those being treated with 'high' doses of diuretics (> or =80 mg/day of furosemide) were more likely to die during follow-up after adjustment for other clinical parameters (adjusted relative risks, RR, 3.1 and 4.6).
Pearls and Pitfalls in the Use and Abuse of Diuretics for Chronic Congestive Heart Failure
Constant J
Cardiology .1999;92(3):156-61
The main purpose of using diuretics is usually lost sight of, i.e. it is for the relief of dyspnea by using the least amount of a diuretic. The production of a low output state and hypercoagulation in an attempt to achieve dry weight by lowering blood volume excessively are among the hazards of using more diuretic than is absolutely necessary to achieve the goal of relieving dyspnea. The use of jugular venous pressure measurement and the status of dyspnea should have precedence over body weight in determining diuretic dose adjustment. Often forgotten in using diuretics is that potassium without magnesium will not enter cells and that the almost universal preference for furosemide over thiazides threatens to increase the incidence of osteoporosis. Also, the tendency to ignore loss of the water-soluble vitamins thiamine and ascorbic acid may result in refractory edema and the inability to manage the stresses of congestive heart failure.
Effects of Short-Acting and Long-Acting Loop Diuretics on Heart Rate Variability in Patients With Chronic Compensated Congestive Heart Failure
Tomiyama H, Nakayama T, Watanabe G, et al
Am Heart J. 1999 Mar;137(3):543-8
Background: We investigated the effects of a short-acting loop diuretic (furosemide) and a long-acting loop diuretic (azosemide) on heart rate variability, fluid balance, and neurohormonal responses in patients with mild to moderate chronic congestive heart failure.
Methods: Nineteen patients with mild to moderate chronic congestive heart failure received furosemide (40 to 60 mg/day) or azosemide (60 to 90 mg/day) for 5 days in a crossover manner. We performed time-domain and frequency-domain analyses of 24-hour Holter electrocardiographic recordings to assess heart rate variability.
Results: The 24-hour urinary sodium excretion was similar during the furosemide and azosemide treatment periods but was significantly greater in the first 2 hours after drug administration during furosemide treatment. Plasma renin activity and the hematocrit level increased and high-frequency power significantly decreased 2 hours after the administration of furosemide only. The standard deviation of all normal R-R intervals and the root mean square of successive differences in the R-R interval were lower with furosemide than with azosemide (P <.05).
Conclusions: Furosemide, a short-acting loop diuretic, has a greater influence on heart rate variability and fluid balance than azosemide, a long-acting loop diuretic, in patients with mild to moderate chronic congestive heart failure.
Nephrocalcinosis in Full-Term Infants Receiving Furosemide Treatment for Congestive Heart Failure: A Study of the Incidence and 2-Year Follow Up
Saarela T, Lanning P, Koivisto M, et al
Eur J Pediatr. 1999 Aug;158(8):668-72
In order to study the incidence and course of nephrocalcinosis in full-term infants with congestive heart failure receiving long-term furosemide treatment, 36 such infants (median age 2.9 months, range 1.2-8.0) and 36 full-term control infants not receiving any diuretics (median age 3.4 months, range 1.1-8.4) were studied by renal ultrasonography and random urine calcium variables. The infants with nephrocalcinosis were followed at 3-6 month intervals up to 2 years of age, or until ultrasonic resolution. Nephrocalcinosis was found in 5 out of the 36 (14%) treated infants, but in none of the controls (P = 0.03). The dose of furosemide was higher in the infants with nephrocalcinosis than in those without (1.9+/-0.6 vs. 1.3+/-0.4 mg/kg per day; P = 0.01). The urinary calcium concentration was higher in the infants receiving furosemide than in controls and a similar trend was observed in the urinary calcium/creatinine ratio, but these variables did not differ between the study infants with and without nephrocalcinosis. Ultrasonic resolution of nephrocalcinosis was observed in 3 of the 5 infants at 12 months, but in the other 2 the condition still persisted at 24 months. CONCLUSIONS: Long-term furosemide treatment in full-term infants with congestive heart failure entails a considerable risk of developing nephrocalcinosis. Renal ultrasonography is warranted in these patients within a few months after initiation of the treatment and in the case of nephrocalcinosis alteration of the diuretic regimen is to be considered.
Diuretic Treatment and Diuretic Resistance in Heart Failure
Kramer BK, Schweda F, Riegger GA
Am J Med. 1999 Jan;106(1):90-6
Diuretic therapy decreases capillary wedge pressure and improves New York Heart Association (NYHA) functional class both in acute and chronic heart failure. In advanced symptomatic heart failure, loop diuretics are generally necessary to improve symptoms of congestion. Diuretic resistance in the edematous patient has been defined as a clinical state in which diuretic response is diminished or lost before the therapeutic goal of relief from edema has been reached. The major causes of diuretic resistance are functional renal failure (prerenal azotemia), hyponatremia, altered diuretic pharmacokinetics, and sodium retention caused by counterregulatory mechanisms intended to reestablish the effective arterial blood volume. Therapeutic approaches to combat diuretic resistance include restriction of fluid and sodium intake, use of angiotensin-converting-enzyme (ACE) inhibitors, changes in route (oral, intravenous) and timing (single dose, multiple doses, continuous infusion) of diuretic therapy, and use of diuretic combinations.