Drugs In Congestive Heart Failure Research Articles

Characterizing Utilization and Outcomes of Digoxin Immune Fab for Digoxin Toxicity.

Digoxin is a widely prescribed drug for congestive heart failure and atrial fibrillation. Digoxin has a narrow therapeutic index and toxicity can develop quite easily. Digoxin immune fab (DIF) is an effective treatment for toxicity, however there are limited studies characterizing its impact on clinical outcomes in real-world clinical practice. The aim of this study was to identify factors and healthcare outcomes associated with digoxin immune fab (DIF) treatment in patients with confirmed/suspected digoxin toxicity. An IRB-approved retrospective chart review of digoxin toxic patients (2011-2020) presenting at an academic healthcare system was conducted. Demographic and clinical data were collected. Patients were stratified by DIF treatment versus non-DIF treatment. DIF utilization patterns (appropriate, use when not indicated, or underutilized) were determined using pre-defined criteria. Severe digoxin toxicity was defined as having one or more of the following: mental status disturbances, antiarrhythmic therapy, acute renal impairment or dehydration, serum digoxin concentration (SDC) > 4ng/mL, or serum K+ > 5mEq/mL. Logistic multivariable regression analysis evaluated factors associated with DIF use. All statistical analyses were performed in R version 4.1. Data from 96 patients (non-DIF treated group = 49; DIF treated group = 47) were analyzed. DIF was used appropriately in 70 patients (73%), underutilized in 19 (20%), and administered to 7 (7%) patients when it was not indicated. Several clinical parameters differentiated the DIF from the non-DIF group (p<0.05) including higher mean SDC (3.41±1.63 vs 2.87±1.17), higher mean potassium (5.33±1.48 vs 4.55±0.87), more toxicity severity (85% vs 49%), and more likely to require cardiac pacing (26% vs 4%). Digoxin toxicity resolved sooner in the DIF group (coefficient - 0.702, 95% CI - 1.137 to - 0.267) (p<0.01) and they had shorter intensive care unit lengths of stay (12.4±20.3 vs 24.4±28.7 days; p=0.018). The all-cause mortality rate in patients appropriately managed with DIF therapy versus those patients where DIF was underutilized was 11% and 21%, respectively. Based on our study population, DIF therapy appears to be beneficial in limiting duration of toxicity and intensive care unit lengths of stay in digoxin toxic patients. Although DIF was appropriately utilized in most cases, there was a relatively high proportion of cases in which DIF treatment was either underutilized or not indicated.

Heart Failure Associated with Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints. Extra-articular features are very common. We report a case of RA first diagnosed after an episode of congestive heart failure (CHF) and the evolution of left ventricular function after conventional treatment of CHF and immunosuppressive drugs. The patient, a 52-year-old man, with history of epilepsy and a stroke 6 years before, presented to the emergency department with increasing dyspnea. He had polyarthralgia 2 months before. The lower extremities had mild pitting edema. The musculoskeletal examination revealed synovial thickening of the metacarpophalangeal and proximal interphalangeal&#x0D; joints, but there was no joint tenderness. The patient’s alanine aminotransferase, troponin levels and CRP were slightly elevated. His renal function was preserved. The electrocardiogram (EKG) was normal. An echocardiogram performed in showed a global hypokinetic dilated cardiomyopathy with an ejection fraction of 15–20%, with apical thrombus. The patient was diagnosed with exacerbation&#x0D; of congestive heart failure (CHF) and was treated with intravenous diuretics. This led to symptomatic improvement. He got a conventional heart failure treatment with vit K antagonists. Coronarography was normal. Viral serologies were negative. The martial, phosphocalcic and thyroid markers were normal. However, the immunologic tests showed positive rheumatoid factor and anti-CCP. The diagnosis of dilated cardiomyopathy due to rheumatoid arthritis was retained. The patient was treated by corticosteroids and immunosuppressive agents. Patient was seen during routine follow-up after 6 months. Interestingly, echocardiographic findings were totally normal with left ventricular ejection fraction &gt;50% and normal LV size.

Digoxin reduces the incidence of prostate cancer but increases the cancer-specific mortality: A systematic review and pooled analysis.

Digoxin, a commonly used drug for congestive heart failure and cardiac arrhythmias, has been reported to exert cytotoxic and apoptosis-inducing effects on prostate cancer (PCa) cells. In this study, we aimed to perform a pooled analysis to summarise all the evidence related to the effects of digoxin on PCa development. Four electronic databases were systematically searched to filter the eligible studies. The hazard ratio (HR) with its 95% confidence interval (CI) was calculated. This study was registered on PROSPERO (ID: CRD42021226885). Ten clinical studies with a total of 108,444 participants (15,835 individuals were digoxin users) were included. The pooled result from 6 included studies demonstrated that digoxin usage was correlated with a significant decrease in PCa risk (adjusted RR=0.892, 95% CI: 0.799-0.997, p=.044) when compared with the nonusers. Synthetic result of 4 eligible studies revealed that digoxin significantly correlated with higher prostate cancer-specific mortality than the controls (adjusted HR=1.142, 95% CI: 1.005-1.297). No statistical heterogeneity was detected during this analysis (all I2 <50%, p>.1). Our study confirmed a preventive effect of digoxin usage for the risk of PCa in men. However, digoxin use was associated with a significantly elevated risk of prostate cancer-specific mortality. This finding needs more well-designed studies to better interpret the causality.

Pharmacodynamic Impact of Carboxylesterase 1 Gene Variants in Patients with Congestive Heart Failure Treated with Angiotensin-Converting Enzyme Inhibitors.

BackgroundVariation in the carboxylesterase 1 gene (CES1) may contribute to the efficacy of ACEIs. Accordingly, we examined the impact of CES1 variants on plasma angiotensin II (ATII)/angiotensin I (ATI) ratio in patients with congestive heart failure (CHF) that underwent ACEI dose titrations. Five of these variants have previously been associated with drug response or increased CES1 expression, i.e., CES1 copy number variation, the variant of the duplicated CES1 gene with high transcriptional activity, rs71647871, rs2244613, and rs3815583. Additionally, nine variants, representatives of CES1Var, and three other CES1 variants were examined.MethodsPatients with CHF, and clinical indication for ACEIs were categorized according to their CES1 genotype. Differences in mean plasma ATII/ATI ratios between genotype groups after ACEI dose titration, expressed as the least square mean (LSM) with 95% confidence intervals (CIs), were assessed by analysis of variance.ResultsA total of 200 patients were recruited and 127 patients (63.5%) completed the study. The mean duration of the CHF drug dose titration was 6.2 (SD 3.6) months. After ACEI dose titration, there was no difference in mean plasma ATII/ATI ratios between subjects with the investigated CES1 variants, and only one previously unexplored variation (rs2302722) qualified for further assessment. In the fully adjusted analysis of effects of rs2302722 on plasma ATII/ATI ratios, the difference in mean ATII/ATI ratio between the GG genotype and the minor allele carriers (GT and TT) was not significant, with a relative difference in LSMs of 0.67 (95% CI 0.43–1.07; P = 0.10). Results of analyses that only included enalapril-treated patients remained non-significant after Bonferroni correction for multiple parallel comparisons (difference in LSM 0.60 [95% CI 0.37–0.98], P = 0.045).ConclusionThese findings indicate that the included single variants of CES1 do not significantly influence plasma ATII/ATI ratios in CHF patients treated with ACEIs and are unlikely to be primary determinants of ACEI efficacy.

ASSA13-13-4 The Impact of Diabetes Mellitus on Short-Term Prognosis of Patients with Congestive Heart Failure

Objective To analyse the effect of Diabetes Mellitus (DM) on 12-month outcomes of Congestive Heart Failure (CHF) patients and to identify risk factors associated with poorer outcomes. Methods A prospective observational study was conducted at a secondary hospital between June 2006 and November 2012. Patients were followed up to 12 months or until death, if earlier. Clinical variables were reviewed and outcomes of mortality or hospitalizations were recorded. Multiple logistics regression was used to identify possible predictors of outcomes. Results Out of 255 patients (46% non-DM, 54% DM), 122 (48%) were hospitalised and 16 (6%) died. All-cause hospitalisation (39% vs 55%; p = 0.012) and composite end-points (cardiovascular-related 33% vs 46%, p = 0.032; all-cause 41% vs 57%, p = 0.010) occurred at a lower rate in non-diabetics than diabetics. A hospitalisation of ≤7 days showed a lower risk of 12-month all-cause mortality (RR = 0.193, p = 0.001). Patients with non-ischemic cardiomyopathy also had a lower risk of all-cause hospitalisation compared to ischemic patients (31% vs 57%; p 7 mmol/L, NYHA Class II, NYHA Class III/IV independently predicted hospitalisation while age and NYHA Class II independently predicted mortality (all p (RR = 2.862, p = 0.013) while no difference was found with Angiotensin Converting Enzyme Inhibitors use. Conclusions CHF patients with DM should be considered as a higher risk group for 12-month all-cause hospitalisation or mortality. This demands better strategies, especially in the optimization of both CHF and DM drug regimens to improve outcomes.

Functional single-cell hybridoma screening using droplet-based microfluidics

Monoclonal antibodies can specifically bind or even inhibit drug targets and have hence become the fastest growing class of human therapeutics. Although they can be screened for binding affinities at very high throughput using systems such as phage display, screening for functional properties (e.g., the inhibition of a drug target) is much more challenging. Typically these screens require the generation of immortalized hybridoma cells, as well as clonal expansion in microtiter plates over several weeks, and the number of clones that can be assayed is typically no more than a few thousand. We present here a microfluidic platform allowing the functional screening of up to 300,000 individual hybridoma cell clones within less than a day. This approach should also be applicable to nonimmortalized primary B-cells, as no cell proliferation is required: Individual cells are encapsulated into aqueous microdroplets and assayed directly for the release of antibodies inhibiting a drug target based on fluorescence. We used this system to perform a model screen for antibodies that inhibit angiotensin converting enzyme 1, a target for hypertension and congestive heart failure drugs. When cells expressing these antibodies were spiked into an unrelated hybridoma cell population in a ratio of 1:10,000 we observed a 9,400-fold enrichment after fluorescence activated droplet sorting. A wide variance in antibody expression levels at the single-cell level within a single hybridoma line was observed and high expressors could be successfully sorted and recultivated.

High Concomitant Use of Interacting Drugs and Low Use of Gastroprotective Drugs among NSAID Users in an Unselected Elderly Population

NSAIDs are commonly used in the elderly and carry significant risks of adverse events when used concomitantly with potentially interacting drugs. The aim of this study was to provide a valid estimate of concomitant use of potentially interacting drugs and gastroprotective agents among elderly NSAID users. This was a nationwide Swedish register-based study of drug prescriptions for 1 529 267 persons aged ≥65 years in 2008, using the Swedish Prescribed Drug Register. The proportions of concomitant use of potentially interacting drugs and gastroprotective agents were analysed among NSAID users, categorized by age group, sex and NSAID use, defined as: non-users, people with 0-30 days of treatment, people with >30-180 days of treatment and people with >180 days of treatment. Use of the following concomitant drugs was evaluated: potentially harmful interacting drugs, i.e. antithrombotic drugs, antihypertensive drugs or drugs for congestive heart failure (digitalis glycosides, thiazide diuretics, loop diuretics, β-adrenoceptor antagonists, calcium channel antagonists, ACE inhibitors and angiotensin II type 1 receptor antagonists [angiotensin receptor blockers]) and other drugs (systemic corticosteroids, selective serotonin reuptake inhibitors [SSRIs], methotrexate and lithium); and gastroprotective drugs. In the study cohort, 257 963 (16.9%) people had collected at least one prescription for an NSAID in 2008. This use was higher in females than in males and decreased in older age groups in both sexes. In the age groups 65-69, 70-74, 75-79, 80-84 and ≥85 years, the frequencies of NSAID users were 20.6%, 20.5%, 18.9%, 15.6% and 11.6% among women, and 16.8%, 16.7%, 15.2%, 13.5% and 11.1% among men, respectively. NSAID users often concomitantly used potentially interacting drugs, e.g. over 30% used antithrombotic agents, and women had higher concomitant use of SSRIs, i.e. 12% compared with 6% in men in the youngest age group. Concomitant use of potentially harmful interacting drugs generally increased with age and with increasing use of NSAIDs. Among the eldest (age ≥85 years), concomitant drug use was stable over NSAID groups. Only 40% of regular NSAID users (i.e. those prescribed NSAIDs for >180 days) were prescribed any gastroprotective medication. Prescribers should be alert to the possibility of potentially harmful interactions between NSAIDs and commonly prescribed drugs in the elderly. Increased use of gastroprotective medication might be justified in this context.

Long-term follow-up after catheter-ablation of atrioventricular junction and pacemaker implantation in patients with uncontrolled atrial fibrillation and heart failure

Atrioventricular (AV) junction ablation coupled with pacemaker implantation is an effective therapeutic option for rate control in atrial fibrillation (AF) and heart failure (HF). However, there is controversy regarding the long-term outcome of the procedure, since right ventricular stimulation can lead to left ventricular remodelling and HF. The aim of the study was to determine a 5-year outcome of the procedure on survival, HF control and myocardial function in patients with HF and uncontrolled AF. All patients with AF and HF who underwent AV-junction ablation with pacemaker implantation in our institution were followed after the procedure. HF diagnosis was established if > or = 2 of the following criteria were present: 1) ejection fraction (EF) < or = 45%; 2) previous episode of congestive HF (CHF); 3) NYHA-class > or = 2; and 4) use of drug-therapy for HF. Study included 32 patients (25 males; 53.4 +/- 9.6 years). The mean heart rate was 121 +/- 25 bpm before and 75 +/- 10 bpm after ablation (p=0.001). Over the follow-up of 5.0 +/- 4.0 years nine patients (28.1%) died (five died suddenly, three of terminal CHF and one of stroke). After the procedure, CHF occurrence was reduced (p=0.001), as well as the annual number of hospitalizations (p=0.001) and the number of drugs for CHF (p=0.028). In addition, NYHA-class and EF were improved, from 3.3 +/- 0.7 to 1.6 +/- 0.8 (p<0.001) and from 39 +/- 11% to 51 +/- 10% (p<0.001), respectively. In HF patients with uncontrolled AF, 5-year mortality after AV-junction ablation and pacemaker implantation was 28%. In the majority of these patients good rate of AF and HF control were achieved, as well as the improvement of functional status and myocardial contractility.

ChemInform Abstract: A Catalytic Enantioselective Synthesis of Denopamine, a Useful Drug for Congestive Heart Failure.

Described here is a practical route to enantiomerically pure (R)-(-)-denopamine or its enantiomer in>60% overall yield that does not involve chromatography. This route demonstrates the applicability of the recently described enantioselective catalytic reduction process to the synthesis of enantiomerically pure members of the therapeutically significant arylethanolamine drug class

064 Temporal trends in prescription rates of recommended treatments in chronic heart failure outpatients: a comparison of three French surveys IMPACT RECO I, II & III

Recent registries have shown that recommended drugs for the treatment of congestive heart failure (CHF) remain under-prescribed in daily practice. To compare prescription rates of CHF drugs in three French surveys Impact Reco I, II and III. We included outpatients followed by private cardiologists: 1947 in Impact Reco I (2005), 1974 in Impact Reco II (2005/2006) and 1574 in Impact Reco III (2007), with NYHA class II-IV heart failure and a left ventricular ejection fraction < 40%, and we compared treatment modalities. Recommended treatments and target doses were defined according to ESC guidelines. There was an improvement in both the rate of prescription, and in the proportion of patients reaching target dose or 50% of target dose of ACE I, ARBs and beta blockers (see table). We observed an improvement with time in the management of CHF outpatients with an increase in prescription rates of recommended CHF drugs, as well as in the dosage used for ACE-I, ARB and beta-blockers, Prescription IMPACT I 2005 IMPACT II 2005/2006 IMPACT III 2007 Global population 1917 1974 1574 ACE I Number patients with prescription N (%) 1361 (71.0) 1349 (68.3) 1099 (70.2) Target dose % 48.7 57.3 * 52.3 • 50% Target dose % 80.4 84.5 * 88.4 † , • ARBs Number patients with prescription N (%) 395 (20.6) 592 (30.0) * 516 (33.3) † , • Target dose % 9.1 7.4 20.7 † , • 50% Target dose % 52.9 49.7 68.6 † , • Betablockers Number patients with prescription N (%) 1245 (65.2) 1382 (70.0) * 1229 (78.3) † , • Target dose % 18.4 23.4 * 25.7 † 50% Target dose % 47.3 53.5 * 59.9 †• * : p<0.05 Impact II vs I • : p<0.05 Impact III vs II † : p<0.05 Impact III vs I although there is still room for improvement particularly for beta blockers. These encouraging findings suggest a better awareness and implementation of ESC guidelines by French private cardiologists.

Effects of candesartan cilexetil “add-on” treatment in congestive heart failure outpatients in daily practice

In the present study, we investigated the efficacy and safety of candesartan cilexetil (candesartan) as "add-on" treatment in congestive heart failure (CHF) in daily practice. In this open-label, multicenter study 414 CHF outpatients (NYHA II/III) with left ventricular ejection fraction (LVEF) < or = 40% and plasma brain natriuretic peptide (BNP) levels > 200 pg/ml at baseline were enrolled. Patients were treated with standard therapy including at least one angiotensin converting enzyme inhibitor in addition to another CHF drug; 91% of the patients received beta-blockers. Candesartan was uptitrated to 32 mg/day (target dose if tolerated) during 6 weeks followed by constant dosing over 16 weeks. The primary endpoint plasma BNP was significantly reduced by 25% at week 22 (from 394 to 295 pg/ml, P < 0.0001 vs. baseline). Candesartan produced early and sustained improvements of plasma BNP/NT-pro-BNP, LVEF, and quality of life (SF-36) compared to baseline. Of patients on beta-blockers, 37% improved towards NYHA II/I at week 22 (P < 0.0001) and 53.5% of the patients in NYHA III at baseline improved into NYHA II/I at week 22 (n = 232, P < 0.0001). Candesartan was well tolerated; no unexpected findings were reported besides known adverse reactions including hypotension, hyperkalemia, and serum creatinine elevations. Candesartan "add-on" treatment provides a good benefit/risk ratio in CHF outpatients in daily practice, although high-risk patients should be managed with frequent monitoring of BP, serum potassium, and renal function.

Safety of the novel atrial-selective K+-channel blocker AVE0118 in experimental heart failure

Congestive heart failure (CHF) is often associated with atrial fibrillation. The safety of many antiarrhythmic drugs in CHF is limited by proarrhythmic effects. We aimed to assess the safety of a novel atrial-selective K(+)-channel blocker AVE0118 in CHF compared to a selective (dofetilide) and a non-selective IKr blocker (terfenadine). For the induction of CHF, rabbits (n = 12) underwent rapid right ventricular pacing (330-380 bpm for 30 days). AVE0118 (1 mg/kg) dofetilide (0.02 mg/kg) and terfenadine (2 mg/kg) were administered in baseline (BL) and CHF. A six-lead ECG was continuously recorded digitally for 30 min after each drug administration. At BL, dofetilide and terfenadine significantly prolonged QTc interval (218 +/- 30 ms vs 155 +/- 8 ms, p = 0.001 and 178 +/- 23 ms vs. 153 +/- 12 ms, p = 0.01, respectively) while QTc intervals were constant after administration of AVE0118 (p = n.s.). In CHF, dofetilide and terfenadine caused torsades de pointes and symptomatic bradycardia, respectively, and prolonged QTc interval (178 +/- 30 ms vs. 153 +/- 14 ms, p = 0.02 and 157 +/- 7 ms vs. 147 +/- 10 ms, p = 0.02, respectively) even at reduced dosages, whereas no QTc-prolongation or arrhythmia was observed after full-dose administration of AVE0118. In conclusion, atrial-selective K(+)-channel blockade by AVE0118 appears safe in experimental CHF.

Genotyping the Future: Scientists' Expectations about Race/Ethnicity after BiDil

The ongoing debate about the FDA approval of BiDil in 2005 demonstrates how the first racially/ethnically licensed drug is entangled in both Utopian and dystopian future visions about the continued saliency of race/ethnicity in science and medicine. Drawing on the sociology of expectations, this paper analyzes how scientists in the field of pharmacogenetics are constructing certain visions of the future with respect to the use of social categories of race/ethnicity and the impact of high-throughput genotyping technologies that promise to transform scientific practices.

Utilization of, and Adherence to, Drug Therapy Among Medicaid Beneficiaries with Congestive Heart Failure

Background: Congestive heart failure (CHF) affects 4.8 million adult Americans, particularly those aged >65 years, and has been described as a “new epidemic” due to the high annual incidence of the disease (an estimated 550,000 new cases per year). Objectives: The goal of this research was to determine the number of Medicaid beneficiaries with CHF, identify the rate of CHF drug use, estimate adherence rates, examine factors associated with CHF drug use and adherence, and explore policy implications of the research findings. Methods: Methods used included identifying noninstitutionalized beneficiaries with >1 inpatient claim or ≥2 ambulatory claims with a CHF diagnosis and claims for CHF drugs using 1998 State Medicaid Research Files and 1999 Medicaid Analytic eXtract data for Arkansas, California, Indiana, and New Jersey. Patient adherence was estimated using the medication possession ratio (MPR) and days of medication persistence. Multivariate regression models were used to identify factors associated with CHF drug use and adherence. Results: Overall, 84.8% of beneficiaries had claims for at least 1 CHF medication; 15.2% of beneficiaries were not using any CHF medications. Among those with a claim, the mean number of claims per month was 1.4, and 25.8% had ≥4 claims per month. Mean MPR was 71.9% and mean days of medication persistence were 24.8 per month. Persons aged <65 years, men, ethnic minorities, patients with hospital admissions for conditions other than CHF, and beneficiaries with high Chronic Illness and Disability Payment System scores were less likely to have a CHF drug claim and had lower adherence rates. Conclusions: State Medicaid agencies and Medicare prescription drug plans should consider designing targeted interventions that encourage better adherence among Medicaid beneficiaries with CHF, particularly men, those aged <65 years, ethnic minorities, and patients with poor overall health status. ( Clin Ther. 2007;29:1771-1783) Copyright © 2007 Excerpta Medica, Inc.

Novel milrinone analogs of pyridine-3-carbonitrile derivatives as promising cardiotonic agents

In an attempt to design new inotropic drugs for congestive heart failure (CHF) with less proarrhythmic potential, three series of compounds analogous to milrinone were prepared, namely, 4-aryl-6-(4-pyridyl)-2-oxo-1,2-dihydropyridine-3-carbonitriles 2a– g, 4-aryl-6-(4-pyridyl)-2-thioxo-1,2-dihydropyridine-3-carbonitriles 3a– g and 2-amino-4-aryl-6-(4-pyridyl)-pyridine-3-carbonitriles 4a– g. The first series was prepared by reacting 4-acetyl pyridine with the appropriate aldehyde, ethyl cyanoacetate and ammonium acetate in ethanol. Reaction of 2a– g with phosphorus pentasulfide afforded the second series 3a– g. The third target compounds 4a– g were prepared applying the same procedure used to synthesize 2a– g using malononitrile instead of ethyl cyanoacetate. All the newly synthesized compounds were evaluated for their cardiotonic activity and their in vivo cardiovascular effects. In addition, their oral and parentral acute toxicity were determined. Compounds 2a, 2b, 2c, 4c and 4f proved to exert cardiotonic activity comparable to that of milrinone using spontaneously beating atria model from reserpine-treated guinea pigs. In addition these compounds proved to be non-toxic and well tolerated by mice up to 250 mg kg –1 orally and up to 125 mg kg –1 through parenteral route.

Association of medication adherence, knowledge, and skills with emergency department visits by adults 50 years or older with congestive heart failure

The association of medication adherence, knowledge, and skills with emergency department (ED) visits by patients 50 years of age or older with congestive heart failure (CHF) was studied. The patients in this study were enrolled in the usual care group of an ongoing trial of patients with CHF to determine the effects of a pharmacy-based intervention on relevant outcomes. Participants' medication knowledge and skills were assessed during individual interviews. Medication knowledge assessed patients' knowledge of the dosage, frequency, and indication of each of their CHF medications. The medications skills assessment evaluated patients' dexterity (ability to open medication bottles), literacy (ability to read labels), and ability to distinguish colors of tablets and capsules. Medication adherence to CHF drugs was calculated from electronic monitors and prescription-refill records over a six-month period. The primary outcomes of this study were the numbers of all-cause cardiovascular and CHF-specific ED visits during a six-month period. Log-linear regression models were used to analyze the effects of medication knowledge, skill, and adherence on ED visits. Sixty-one patients participated in this study. Multivariate log-linear models adjusted for demographic variables showed that lower medication adherence (p < 0.001) and an inability to read standard prescription and auxiliary labels (p = 0.002) were associated with an increased number of cardiovascular-related ED visits. Knowledge of the prescribed dose was associated with CHF-specific ED visits (p < 0.001). Greater medication knowledge, skills, and adherence were associated with fewer ED visits among patients 50 years of age or older with CHF in an urban, teaching medical center.

The effects of spironolactone on thiamine blood levels in patients with congestive heart failure on chronic high doses of loop-diuretics

Background: The nonpharmacological management of congestive heart failure (CHF) has been understudied. The importance of micronutrients such as vitamin B1 (thiamine) has long been known since its deficiency is associated with the development of high-output CHF. In the present study, we studied the relationship between adding to ACE inhibition further aldosterone suppression with spironolactone and thiamine blood levels (pmol/ml). Methods: A total of 22 patients (pts) with moderate to severe CHF symptoms (NYHA II/IV) were divided in two groups according to the use of spironolactone [group I-spironolactone 25 mg/qd (n 11) and group II no spironolactone (n 11)]. Thiamine blood levels were determined using the erythrocyte transketolase activity. The groups were compared regarding food intake, furosemide doses, demographics and thiamine blood levels (mean SD) using a student’s t test. Chi-square and Kruskal-Wallis tests were used to assess variables associated with thiamine levels. Results: Group I and II were similar regarding food intake, daily furosemide doses (110.9 30.2 and 105.5 26.9 mg, respectively; p 0.05), demographics (etiology of CHF, age, hypertension, diabetes, smoking, alcohol abuse, dyslipidemia and adjuvant drug CHF treatment). Patients in group I showed significantly higher thiamine blood levels when compared to patients in group II (277.2 89.8 and 154.7 35.7 pmol/ml, respectively) (p 0.001). None of the dependent variables cited above were associated with thiamine blood levels. Conclusion: In a cohort of ambulatory CHF patients (NYHAII/IV) on high doses of loop diuretics the use of spironolactone is associated with higher thiamine blood levels. The significance of this finding remains to be established by future studies with prospective design and larger sample sizes. Safety and Efficacy of Intermittent, Short-Term, Outpatient Nesiritide Infusions for the Treatment of Decompensated Heart Failure Ghaith M. Mulki, Carol Pisano, Gallagher Colleen, Cianci Pamela, Muhyaldeen Dia, Marc A. Silver1—Department of Medicine and the Heart Failure Institute, Advocate Christ Medical Center, Oak Lawn, IL

Heart failure in a multiethnic population in Kuala Lumpur, Malaysia.

There are established differences in cardiovascular disease in different racial groups. Worldwide, the literature regarding the clinical epidemiology of congestive heart failure (CHF) in non-white populations is scarce. To document the prevalence of CHF in the multiracial population of Malaysia, and to describe the clinical features and management of these patients. Busy city centre general hospital in Kuala Lumpur, Malaysia. Of 1435 acute medical admissions to Kuala Lumpur General Hospital over the 4-week study period, 97 patients (6.7%) were admitted with the primary diagnosis of CHF. Coronary artery disease was the main aetiology of CHF, accounting for almost half (49.5%) the patients, followed by hypertension (18.6%). However, there were variations in associated aetiological factors between ethnic groups, with diabetes mellitus affecting the majority of Indians-as well as underutilisation of standard drugs for CHF, such as the angiotensin converting enzyme (ACE) inhibitors, which were only used in 43.3%. Amongst acute medical admissions to a single centre in Malaysia the prevalence of CHF was 6.7%. Coronary artery disease was the major aetiological factor in heart failure accounting for almost half the admissions. The under-prescription of ACE inhibitors was similar to other clinical surveys carried out amongst Caucasian populations in the West.

Analysis of medication use patterns:apparent overuse of antibiotics and underuse of prescription drugs for asthma, depression, and CHF.

To assess the appropriateness of prescription medication use based upon widely accepted treatment guidelines. We analyzed administrative claims for the period October 1, 1998, through September 20, 1999, supplied by 3 California health plans to determine medication use patterns for outpatient prescriptions. We compared these patterns to those expected in the presence of adherence to treatment guidelines. During the study period, only 27.5% of antidepressant users received the recommended 6 months of continuous therapy, only 49.0% of diagnosed asthma patients received at least one inhaled corticosteroid prescription (compared to 67.1% who received at least one inhaled beta-agonist prescription), and only 54.5% of patients diagnosed with congestive heart failure (CHF) received an angiotensin-converting enzyme (ACE) inhibitor. Of patients who had a diagnosis of common cold or upper respiratory tract infection, 35.7% received antibiotics. There is a remarkable degree of apparent overuse and underuse of prescription medications despite the existence of clinical guidelines to support appropriate use in the conditions studied. Effective medications appear to be underused for patients with asthma, CHF, and depression. Antibiotics appear to be overused for the common cold and upper respiratory infections. More effective efforts must be made to address appropriate use of medications. Without these efforts, improved quality of care and decreased total health system costs are unlikely to be realized.

Warfarin Induced Skin Necrosis: Presentation of Two Cases

Skin necrosis is an uncommon complication of warfarin therapy. Painful skin lesions are initially erythematous and hemorrhagic; they become bullous and eventually proceed to gangrenous necrosis. We present two cases with skin necrosis due to warfarin use. The first patient was a 72-year-old man who was admitted with abdominal pain and dyspnoea. He was on warfarin for atrial fibrillation, as well as other cardiac and respiratory drugs for congestive heart failure and atrial fibrillation. He had purpural rashes on his lower limbs. Warfarin treatment was ceased because of skin necrosis formation and he died from cardiogenic shock in the intensive care unit. The second patient was a 66-year-old female with recurrent bilateral lower extremity swelling. She had been using warfarin 10 mg/day for 15 days for the treatment of deep vein thrombosis. She had necrotic and bullous lesions on her left lower limb. Treatment of the lesion was wet to dry dressings soaked with zinc for 10 days and warfarin treatment was replaced with low molecular weight heparine 2 mg/kg/day. Because of the deep vein thrombosis, a vena cava filter was placed by invasive radiologists for pulmonary embolism prophylaxis. She was discharged without any complications.