Lipid management among coronary artery disease patients with diabetes mellitus or advanced age.

Aggressive lipid management is likely beneficial for coronary artery disease patients with diabetes mellitus or of advanced age. Nevertheless, a study of a large national sample of patients seen in ambulatory medical practices suggests pharmacologic undertreatment in these high-risk groups.

Effect of angiotensin-converting enzyme inhibitor therapy on 30-day outcome in patient > or = 65 years of age with chronic congestive heart failure.

Patients discharged from the hospital on an angiotensin-converting enzyme inhibitor had a significant decrease in 30-day death or readmission (by 30% in 1,195 unselected Medicare patients hospitalized with congestive heart failure). Other independent predictors of poor outcome determined by multivariate analysis included history of congestive heart failure, male gender, increased number of comorbidities, higher serum blood urea nitrogen, and lower serum sodium.

Association of body mass, gender and race with heart failure primarily due to hypertension.

OBJECTIVES: This study was performed to determine the association between clinical characteristics, particularly body mass and race, and the likelihood of hypertension as the primary etiology for heart failure (HTNCM). BACKGROUND: Although held to be important in the development of heart failure, the clinical characteristics predictive of HTNCM have not been well delineated. METHODS: The study analysis was conducted using 680 patients from the University of North Carolina Heart Failure Database. This data set is racially diverse (44% African-American) and contains data concerning baseline clinical characteristics and cardiac function in patients with and without HTNCM. Logistic regression techniques determined independent predictors of HTNCM among the entire study population as well as the subgroup of study patients with hypertension. RESULTS: Hypertension was present in 51% of the study patients but was the primary etiology of heart failure in only 25%. Body mass, race, gender and baseline systolic blood pressure were identified as significant independent predictors of the likelihood of HTNCM (all p < 0.001). These characteristics were predictors in the total study population and also in the subgroup of study patients with hypertension. CONCLUSIONS: Hypertension remains a common etiologic factor for the development of heart failure but was the primary cause of heart failure in a minority of study patients. However, the presence of increased body mass, female gender, African-American ethnic origin or elevated baseline systolic blood pressure significantly increased the likelihood of HTNCM.

Analysis of the degree of undertreatment of hyperlipidemia and congestive heart failure secondary to coronary artery disease.

There is a lack of data evaluating the implementation of guidelines in the management of coronary artery disease (CAD) or congestive heart failure (CHF) in the outpatient setting. We analyzed an administrative data set from the Merck & Co. sponsored national Quality Assurance Program, a retrospective outpatient chart audit of 58,890 adult outpatients from 140 medical practices (80% cardiology only) in the USA with diagnoses of CAD and/or CHF identified from medical claims data. We determined the (1) frequency of lipid documentation and prescription of lipid-lowering agents in patients with CAD, (2) frequency of assessment of left ventricular function and prescription of an angiotensin-converting enzyme inhibitor in patients with CHF, and (3) predictors of medication prescription. Of the 48,586 patients with CAD, 44% had annual diagnostic testing of low-density lipoprotein cholesterol. Only 25% of these patients reached the target low-density lipoprotein cholesterol of < or = 100 mg/dl, and only 39% were taking lipid-lowering therapy, which was less among the elderly than in the younger patients. Of the 16,603 patients with CHF, 64% had diagnostic testing of left ventricular function, and 50% of patients were taking an angiotensin-converting enzyme inhibitor; 67% of patients received medication if they had documented systolic dysfunction. Significant predictors of medication prescription included diagnostic testing, younger age, history of myocardial infarction or coronary artery bypass grafting, hypertension, cardiology specialty, and geographic region. Thus, current practice patterns in the management of CAD and CHF are inadequate. Patient age, diagnostic testing, and practice environment influence medication prescription.

Gender differences in survival in advanced heart failure. Insights from the FIRST study.

BACKGROUND: Previous natural history studies in broad populations of heart failure patients have associated female gender with improved survival, particularly in patients with a nonischemic etiology of ventricular dysfunction. This study investigates whether a similar survival advantage for women would be evident among patients with advanced heart failure. METHODS AND RESULTS: The study analysis is based on the Flolan International Randomized Survival Trial (FIRST) study which enrolled 471 patients (359 men and 112 women) who had evidence of end-stage heart failure with marked symptoms (60% NYHA class IV) and severe left ventricular dysfunction (left ventricular ejection fraction 18+/-4.9%). A Cox proportional-hazards model, adjusted for age, gender, 6-minute walk, dobutamine use at randomization, mean pulmonary artery blood pressure, and treatment assignment, showed a significant association between female gender and better survival (relative risk of death for men versus women was 2.18, 95% CI 1.39 to 3.41; P<0.001). Although formal interaction testing was negative (P=0.275), among patients with a nonischemic etiology of heart failure, the relative risk of death for men versus women was 3.08 (95% CI 1.56 to 6.09, P=0.001), whereas among those with ischemic heart disease, the relative risk of death for men versus women was 1.64 (95% CI 0.87 to 3.09, P=0.127). CONCLUSIONS: Women with advanced heart failure appear to have better survival than men. Subgroup analysis suggests this finding is strongest among patients with a nonischemic etiology of heart failure.

Performance assessment model for guideline-recommended pharmacotherapy in the secondary prevention of coronary artery disease and treatment of left ventricular dysfunction.

The Agency for Health Care Policy and Research, the National Heart Lung and Blood Institute of the National Institutes of Health, the American Heart Association, and the American College of Cardiology have all developed guidelines for improving the care of patients with cardiovascular disease. The guidelines include recommendations for intensive lipid-lowering therapy in patients with coronary artery disease (CAD) and angiotensin-converting enzyme (ACE) inhibitors in those patients with symptomatic heart failure and asymptomatic left ventricular dysfunction. Despite clinical trial evidence and consensus that these therapies improve survival in high-risk patients, data suggest that there is wide variation in the delivery of guideline-based care. To investigate whether evidence-based assessment of provider practice patterns can impact the delivery of quality cost-effective care, Merck and Company, in conjunction with leading cardiology group practices, the University of North Carolina at Chapel Hill, and Medical Review of North Carolina developed an ambulatory medical record abstraction study. This quality assurance initiative was conducted at practices beginning in the spring of 1996 and continues. Medical records and administrative claims of patients with ischemic heart disease or heart failure were abstracted by a healthcare consulting organization to maintain patient and physician confidentiality. As of mid-July 1997, 626 group practices had completed the medical record abstraction process, with > 1,136 practices participating at some stage of the project; >6,000 physicians participated in the project and >270,000 patients charts were abstracted. Analysis of these data will provide insight and benchmark patterns of care in the pharmacologic management of heart failure and CAD. This project represents a unique collaboration between a pharmaceutical company, an academic institution, a Peer Review Organization, and practicing physicians, to support evidence-based best medical practices.

Improving care for unstable angina patients in a multiple hospital project sponsored by a federally designated quality improvement organization.

In 1992, the Health Care Financing Administration (HCFA) implemented a major change in the methodology of the quality of care oversight activities conducted by Medicare Peer Review Organizations. The Health Care Quality Improvement Program (HCQIP) represented a shift in oversight activity direction from identifying and dealing with individual clinical errors to helping providers improve mainstream care. The change in the oversight activities of Peer Review Organizations has been so substantial that the organizations are now commonly referred to as Quality Improvement Organizations (QIOs). Since its introduction, the HCQIP has developed multiple cooperative projects between QIOs and participating hospitals to examine specific processes of care and to ultimately improve the quality of care provided to Medicare patients. This report describes one project in North Carolina focusing on inpatient treatment of patients with a principal diagnosis of unstable angina, one of the most frequent causes of hospital admissions for Medicare patients. Based on the guidelines for treating unstable angina issued by the Agency for Health Care Policy and Research, 5 measures of good medical care for these patients were selected as quality of care indicators. A total of 16 hospitals in North Carolina each provided medical records of approximately 50 Medicare patients discharged with a principal diagnosis of unstable angina. Our findings indicated that guidelines-recommended standard of care were met in only a minority of patients. These indicators of care--including ordering an electrocardiogram within the first hour of admission and admitting high-risk patients to the intensive care unit--all occurred in <50% of the patients. Moreover, use of drugs that improve outcomes in patients with unstable angina was lower than expected. Only 17% of eligible patients with unstable angina were discharged on a lipid-lowering medication. Although there was variation in compliance with the guidelines between types of hospitals, all hospitals had an opportunity to improve in at least one quality of care indicator. The data demonstrate that significant variances exist between published guidelines and actual practices. Given the high rates of readmission for patients with coronary disease, there is opportunity to improve compliance with recommended guidelines of good care. The new oversight activity direction taken by Medicare should ultimately improve care for more patients than could ever be achieved through individual case review.

Relation between gender, etiology and survival in patients with symptomatic heart failure.

OBJECTIVES: This study investigated the relation between gender, etiology and survival in patients with symptomatic heart failure. BACKGROUND: Previous work provides conflicting results concerning the relation between gender, clinical characteristics and survival in patients with heart failure. METHODS: We examined the relation of these factors in 557 patients (380 men, 177 women) who had symptomatic heart failure, predominantly nonischemic in origin (68%) and typically associated with severe left ventricular dysfunction. RESULTS: Follow-up data were available in 99% of patients (mean follow-up period 2.4 years, range 1 day to 10 years) after study entry, and 201 patients reached the primary study end point of all-cause mortality. By life-table analysis, women were significantly less likely to reach this primary end point than men (p < 0.001). A significant association was found between female gender and better survival (p < 0.001), which depended on the primary etiology of heart failure (p = 0.008 for the gender-etiology interaction) but not on baseline ventricular function. Women survived longer than men when heart failure was due to nonischemic causes (men vs. women: relative risk [RR] 2.36, 95% confidence interval [CI] 1.59 to 3.51, p < 0.001). In contrast, outcome appeared similar when heart failure was due to ischemic heart disease (men vs. women: RR 0.85, 95% CI 0.45 to 1.61, p = 0.651). CONCLUSIONS: Women with heart failure due to nonischemic causes had significantly better survival than men with or without coronary disease as their primary cause of heart failure.

Antiarrhythmic action of pharmacological administration of magnesium in heart failure: a critical review of new data.

Congestive heart failure is characterized by contractile dysfunction and frequent complex ventricular ectopy. Despite advances in therapy, mortality from heart failure is substantial, estimated at 10-80 percent per year, and sudden death is common. Magnesium is the second most common intracellular cation, strongly influences cardiac cell membrane function, and is an important catalyst of many enzymatic reactions in the myocyte. Epidemiological studies have implicated magnesium deficit in the genesis of sudden death. Patients with congestive heart failure are predisposed to magnesium deficit for many reasons, including neurohormonal activation, poor gastrointestinal absorption, and drug therapy. Hypomagnesaemia is common in these patients and has been linked to an increased frequency of complex ventricular ectopy. Several early, uncontrolled studies have suggested a beneficial effect of magnesium administration on ventricular arrhythmias in patients with congestive heart failure. Two recent randomized, double blind, placebo-controlled trials have shown that both intravenous and oral administration of magnesium chloride results in a significant reduction in the frequency and complexity of ventricular arrhythmias in patients with congestive heart failure. Magnesium administration is well tolerated and serious adverse effects are rare. The potential mechanisms of the antiarrhythmic action of magnesium and limitations of the available data are discussed. The evidence reviewed suggests that serum magnesium concentrations should be monitored and corrected in patients with congestive heart failure. Ventricular arrhythmias may respond to acute intravenous magnesium administration, which should be considered as early therapy. Further study is needed to define magnesium dose and the effect of concomitant potassium administration. A prospective clinical trial is warranted to determine the chronic effects of magnesium administration in patients with heart failure.

Acute hemodynamic effects of the prostacyclin analog 15AU81 in severe congestive heart failure.

This multicenter, open-label study provides the first assessment of the safety and acute hemodynamic effects of a short-term infusion of 15AU81, a chemically stable analog of prostacyclin, in patients with New York Heart Association class III or IV heart failure. Twelve patients underwent sequential dose escalation by increasing the rate of the infusion at 15-minute intervals until the drug was no longer tolerated. Patients then received a 90-minute infusion at their maximum tolerated dose. The infusion was then discontinued and the subjects were observed during a 90-minute washout segment. Serial hemodynamic measurements were made throughout the dose-ranging, maintenance, and washout segments. A significant decrease in systemic vascular resistance (1,935 +/- 774 vs 1,243 +/- 351 dynes.s.cm-5; p < 0.001) and pulmonary vascular resistance (395 +/- 335 vs 223 +/- 198 dynes.s.cm-5; p = 0.008) occurred from the infusion of vehicle to the maximum tolerated dose. During dose titration, there was a a significant increase in cardiac index (1.9 +/- 0.7 vs 2.6 +/- 0.6 liters/min/m2; p < 0.001) and a tendency for a mild reduction in pulmonary artery wedge pressure (18 +/- 7 vs 17 +/- 6; p = 0.055) for the 8 patients with values on vehicle and maximum tolerated dose. These hemodynamic changes persisted during the maintenance infusion and disappeared rapidly during the washout segment. The most common adverse event to limit dose-ranging was headache, which occurred at a mean maximum tolerated dose of 36 +/- 15 ng/kg/min. Administration of 15AU81 was associated with significant acute hemodynamic improvement in patients with severe heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Safety and efficacy of epoprostenol in patients with severe congestive heart failure. Epoprostenol Multicenter Research Group.

Patients with advanced heart failure often remain severely symptomatic and have a high mortality rate despite currently available therapy. We studied the safety and efficacy of a new approach to the patient with refractory heart failure: continuous intravenous treatment via a portable infusion pump with epoprostenol (prostacyclin), a potent pulmonary and systemic vasodilator. A group of 33 patients with severe heart failure (64% New York Heart Association class IV and 36% class III) and profound ventricular dysfunction (median left ventricular ejection fraction, 0.15)--despite prior treatment with diuretics (100%), digitalis (91%), angiotensin-converting enzyme inhibitors (85%), and dobutamine (30%)--underwent a baseline 6-minute walk test prior to dose titration with epoprostenol during invasive hemodynamic monitoring. Subjects responding during the dose titration were randomized, on an open basis, to receive either continuous epoprostenol infusion via an indwelling central venous catheter plus conventional therapy or conventional therapy alone for 12 weeks. The initial dose-ranging study with epoprostenol produced a significant decline in systemic and pulmonary vascular resistance and a substantial increase in cardiac index despite a fall in pulmonary capillary wedge pressure. Symptoms related to vasodilation were noted within the first week after randomization to epoprostenol in 9 of 16 patients but resolved with adjustment of the infusion and concomitant medications in all but one subject. Dose adjustments during the chronic epoprostenol infusion were infrequent after the first week and complications related to the drug delivery system were rare. The change in distance walked from baseline to the last available 6-minute walk test was significantly greater in patients who received epoprostenol compared with patients assigned to standard therapy (72 +/- 40 vs -39 +/- 32 m, mean +/- SEM; p = 0.033). Our study suggests that long-term intravenous infusion of epoprostenol is feasible in patients with severe heart failure and our hemodynamic and functional results suggest clinical benefit as well. However, until recent results indicating an adverse effect of epoprostenol on survival are fully evaluated, the role of this drug in the treatment of advanced heart failure will remain uncertain.

Effect of acute magnesium administration on the frequency of ventricular arrhythmia in patients with heart failure.

BACKGROUND: There is a high incidence of ventricular arrhythmia and sudden death in patients with heart failure. Unfortunately, currently available antiarrhythmic agents have only limited efficacy and may result in proarrhythmia and hemodynamic deterioration in these patients. METHODS AND RESULTS: We studied the acute effect of intravenous magnesium chloride on the frequency and severity of ventricular arrhythmia in 30 patients with symptomatic heart failure using a double-blind, placebo-controlled crossover design. The left ventricular ejection fraction was 23.0 +/- 8.0% (mean +/- SD). No patient had a history of symptomatic ventricular arrhythmia or was receiving antiarrhythmic agents, calcium channel antagonists, or beta-blockers. Patients were randomized to receive placebo (5% dextrose [D5W] in water alone) or magnesium chloride in D5W given as a bolus of 0.3 mEq/kg over 10 minutes followed by a maintenance infusion of 0.08 mEq/kg per hour for 24 hours. The magnesium concentrations 30 minutes and 24 hours after the bolus were 3.6 +/- 0.1 and 4.2 +/- 0.1 mg/dL, respectively. There was no significant change in serum potassium concentration during magnesium administration. Blinded analysis revealed that administration of intravenous magnesium chloride, compared with placebo, significantly decreased total ventricular ectopy per hour (mean +/- SEM, 70 +/- 26 versus 149 +/- 64, P < .001), couplets per day (23 +/- 11 versus 94 +/- 59, P = .007), and episodes of ventricular tachycardia per day (0.8 +/- 0.2 versus 2.6 +/- 1.0, P = .051). CONCLUSIONS: Intravenous magnesium chloride administration reduces the frequency of ventricular arrhythmia in patients with symptomatic heart failure.

Reassessment of indications for digoxin. Are patients being withdrawn?

Several studies have shown that the majority of patients receiving digoxin can be successfully withdrawn. A medical record review was conducted to determine whether, in practice, patients were being withdrawn from digoxin. Original indications for digoxin therapy in 163 outpatients were as follows: congestive heart failure (CHF), 50%; supraventricular tachycardia (SVT), 23%; CHF and SVT, 10%; and unknown/unclear, 17%. One third of these patients were withdrawn during the 3.5-year study, and 79% remained stable, off digoxin. The most significant predictor of withdrawal was chart indication of reassessment of the need for digoxin. The majority of the patients (68%) were reassessed, and of these, almost half were withdrawn. Physicians appear to be reassessing the need for digoxin therapy, resulting in higher withdrawal rates than previously reported. Results suggest that patients with unclear original indications, a onetime indication, or without clinical evidence of CHF or SVT can be successfully withdrawn.

A microcirculatory technique for evaluating intravascular and topical administration of vasoactive agents: response to AVP in the SHR.

A "closed bath" cremaster muscle preparation is described which permits the administration of vasoactive materials to the microvasculature via intraarterial injection and topical suffusion. The technique is evaluated in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats by comparing arteriolar responses to intraarterial and topically suffused arginine vasopressin. The preparation utilizes a thermostatically heated brass suffusion chamber overlying the cremaster. The chamber is closed with a glass coverslip. Experimental materials are presented to the microvessels via intraarterial injection or suffusion through the chamber. The coverglass permits high optical resolution with both routes of administration. Following vasopressin administration, changes in arteriolar diameter were continuously monitored by image-shearing techniques or variable-resistance calipers. The responses were analyzed by comparing both the peak 5-sec vasoconstriction and a 60-sec integrated response. Intraarterial and topical suffusion of vasopressin (1.25 X 10(-10)-3.75 X 10(-7) M) caused dose-dependent vasoconstriction among 23-microns arterioles. Compared to the WKY, vasoconstriction was greater in the SHR when vasopressin was administered intraarterially. A similar strain difference was not observed with topical suffusion. The dose-response curves with intraarterial vasopressin were shifted approximately 100-fold in concentration to the right relative to those with topically suffused vasopressin. The "closed bath" cremaster muscle preparation described has several distinct advantages: (1) it permits introduction of different vasoactive materials in the most physiological manner in the same animal, and (2) it maintains high optical resolution and clarity for critical observation of the smallest vessels, even with suffusion.

Norepinephrine-induced potentiation of arginine vasopressin reactivity in arterioles of the spontaneously hypertensive rat.

We have studied microvascular reactivity to vasopressin alone and in combination with norepinephrine in young (6- to 8-week-old) spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) controls. Closed-circuit TV microscopy was used to quantify the in vivo diameter responses of small arterioles (17 to 26 mu) to vasopressin (1.25 X 10(-8) to 3.75 X 10(-7) M) injected intraarterially alone and with simultaneous topical suffusion of a subthreshold concentration of norepinephrine in the cremaster muscle microcirculation. Percent decrease in luminal diameter was integrated over a 30-second period to obtain log concentration response curves. The vasoconstrictor response to vasopressin was concentration-dependent in both groups (p less than 0.001). A significant increase in reactivity to vasopressin alone was exhibited by the SHR arterioles compared to the WKY vessels (p less than 0.02). Maximum constriction was 55% higher in the SHR (p less than 0.04). The SHR also demonstrated a greater sensitivity to vasopressin (p less than 0.02). Vasopressin-induced vasoconstriction was potentiated by norepinephrine in the SHR, demonstrated by the significant shift of the curve up and to the left of the SHR response curve to vasopressin alone (p less than 0.01). The maximum response was 38% greater (p less than 0.02). Sensitivity was significantly enhanced (p less than 0.01). Additionally, the presence of norepinephrine stimulated a three-fold greater incidence of complete closure. In contrast to SHR results, topical suffusion of norepinephrine did not significantly alter the reactivity of the WKY arterioles to vasopressin-induced constriction. Our results support a role for vasopressin as a potential vasoconstrictor in the developing stage of SHR hypertension which may be modulated by norepinephrine and thus contribute to the elevated total peripheral resistance observed.