Identification of risk factors for increased cost, charges, and length of stay for cardiac patients.

BACKGROUND: In this study we explored different risk model options to provide clinicians with predictions for resource utilization. The hypotheses were that predictors of mortality are not predictive of resource consumption, and that there is a correlation between cost estimates derived using a cost-to-charge ratio or a product-line costing approach. METHODS: From March 1992 to June 1995, 2,481 University of Colorado Hospital patients admitted for ischemic heart disease were classified by diagnosis-related group code as having undergone or experienced coronary bypass procedures (CBP), percutaneous cardiovascular procedures (PCVP), acute myocardial infarction (AMI), and other cardiac-related discharges (Other). For each diagnosis-related group, Cox proportional hazards models were developed to determine predictors of cost, charges, and length of stay. RESULTS: The diagnosis groups differed in the clinical factors that predicted resource use. As the two costing methods were highly correlated, either approach may be used to assess relative resource consumption provided costs are reconciled to audited financial statements. CONCLUSIONS: To develop valid prediction models for costs of care, the clinical risk factors that are traditionally used to predict risk-adjusted mortality may need to be expanded.

War trauma experience and behavioral screening of Bosnian refugee children resettled in Massachusetts.

The authors assessed war violence exposure and behavioral symptoms in Bosnian refugee children in Massachusetts and the utility of behavioral screening of refugees during the Refugee Health Assessment (RHA), required of newly arrived refugees. The study was a survey of 31 Bosnian refugee children in 1996 at the International Clinic of Boston Medical Center, the state's largest contracted provider of the RHA. Subjects were also offered referrals to appropriate mental health services. Sixty-eight percent experienced long-term separation from a parent. Eighty-one percent were directly exposed to armed combat. Seventy-one percent experienced the death of a close friend or relative. Fifty-two percent experienced economic deprivation. Families reported behavioral symptoms for 77% of children. Only one family expressed interest in psychosocial services of any kind. Large numbers of Bosnian refugees are likely to have experienced traumatic war violence and are at risk of behavioral symptoms. The RHA affords opportunities to screen for behavioral problems but not to intervene. Primary care providers and other clinicians should be aware of likely recurrences of symptoms in high-risk children such as these.

Computerized left ventricular pressure-volume relationships (pV-loops) using disposable angiographic tip transducer pigtail catheters.

Left ventricular pressure-volume relationships expressed as pV loops could yield important hemodynamic information in the cardiac catheterization laboratory. Many clinical situations might benefit from a quantitative assessment of left ventricular function. Potential applications of pV loops include the assessment of vasoactive and inotropic drugs, balloon valvuloplasty, coronary angioplasty, and surgical treatment of valvular heart disease. For many years the clinical use of pV loops has been hindered by logistical difficulties. The ability to merge on-line concurrent digital imaging data for computation of left ventricular volume and digital left ventricular pressure wave forms obtained from high fidelity tip-transducer angiocatheters has allowed us to develop a technique which can generate pV loops during cardiac catheterization procedures. The method offers an automated measurement of left ventricular volume independent of edge detection or an interactive technique for tracing endocardial borders by a trained operator. Illustrative case studies are included to demonstrate the potential of the method during ventricular angiographic procedures. Implementation and computational time requirements of the method are discussed. The concept and the value of pV loop generation to study left ventricular performance has been known for many years. Combining digital imaging and digital physiologic data obtained with disposable tip-transducer angiocatheters with modern networking technology, the technique can more easily be applied to catheterization procedures and could enhance invasive hemodynamic assessment of left ventricular function.

Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial.

BACKGROUND: Pulmonary hypertension is a progressive and often fatal complication of the scleroderma spectrum of disease for which no treatment has been proven effective in a randomized trial. OBJECTIVE: To determine the effect of epoprostenol on pulmonary hypertension secondary to the scleroderma spectrum of disease. DESIGN: Randomized, open-label, controlled trial. SETTING: 17 pulmonary hypertension referral centers. PATIENTS: 111 patients with moderate to severe pulmonary hypertension. INTERVENTION: Epoprostenol plus conventional therapy or conventional therapy alone. MEASUREMENTS: The primary outcome measure was exercise capacity. Other measures were cardiopulmonary hemodynamics, signs and symptoms of pulmonary hypertension and scleroderma, and survival. RESULTS: Exercise capacity improved with epoprostenol (median distance walked in 6 minutes, 316 m at 12 weeks compared with 270 m at baseline) but decreased with conventional therapy (192 m at 12 weeks compared with 240 m at baseline). The difference between treatment groups in the median distance walked at week 12 was 108 m (95% CI, 55.2 m to 180.0 m) (P < 0.001). Hemodynamics improved at 12 weeks with epoprostenol. The changes in mean pulmonary artery pressure for the epoprostenol and conventional therapy groups were -5.0 and 0.9 mm Hg, respectively (difference, -6.0 mm Hg [CI, -9.0 to -3.0 mm Hg), and the mean changes in pulmonary vascular resistance were -4.6 and 0.9 mm Hg/L per minute, respectively (difference, -5.5 mm Hg/L per minute [CI, -7.3 to -3.7 mm Hg/L per minute). Twenty-one patients treated with epoprostenol and no patients receiving conventional therapy showed improved New York Heart Association functional class. Borg Dyspnea Scores and Dyspnea-Fatigue Ratings improved in the epoprostenol group. Trends toward greater improvement in severity of the Raynaud phenomenon and fewer new digital ulcers were seen in the epoprostenol group. Four patients in the epoprostenol group and five in the conventional therapy group died (P value not significant). Side effects of epoprostenol therapy included jaw pain, nausea, and anorexia. Adverse events related to the epoprostenol delivery system included sepsis, cellulitis, hemorrhage, and pneumothorax (4% incidence for each condition). CONCLUSIONS: Continuous epoprostenol therapy improves exercise capacity and cardiopulmonary hemodynamics in patients with pulmonary hypertension due to the scleroderma spectrum of disease.

Hyperuricemia in severe pulmonary hypertension.

STUDY OBJECTIVE: Hyperuricemia occurs frequently in patients with myeloproliferative and lymphoproliferative disorders and in patients with congenital heart disease associated with polycythemia. Whether hyperuricemia is common in patients with severe pulmonary hypertension is not known. DESIGN, PATIENTS, MEASUREMENTS: In the Pulmonary Hypertension Center at the University of Colorado Health Sciences Center between September 1991 and August 1997, 442 consecutive patients were evaluated with right heart catheterization; 191 patients also had a measurement of the serum uric acid (UA) in close temporal proximity to the hemodynamic evaluation. RESULTS: Of the 191 patients with a complete data set, 99 patients had primary pulmonary hypertension (PPH) and 92 had secondary pulmonary hypertension. For the entire cohort with severe pulmonary hypertension (n = 191), there was a positive correlation between the natural logarithm of the serum UA (lnUA) and the mean right atrial pressure (RAP; r = 0.47; p < 0.001). When analyzed separately, the correlation between lnUA and RAP was stronger in the patients with PPH (r = 0.642; p < 0.001). This correlation cannot be explained by diuretic use or impaired hepatocellular function. Neither mean pulmonary artery pressure nor cardiac output was as well correlated with the RAP when compared with the lnUA. Some patients with PPH had serum UA measurements repeated during treatment with chronic IV prostacyclin infusion. Eleven of these 18 patients (61%) demonstrated a decrease in serum UA during prostacyclin treatment. CONCLUSION: There is a positive correlation between the RAP elevation and the serum UA levels in patients with PPH. Serum UA levels drop in some, but not all PPH patients during chronic prostacyclin infusion therapy.

3D coronary reconstruction from routine single-plane coronary angiograms: clinical validation and quantitative analysis of the right coronary artery in 100 patients.

BACKGROUND: Current coronary angiographic techniques display complex three-dimensional (3D) coronary structures in two dimensions (2D). We have developed a 3D reconstruction (3DR) algorithm using standard single-plane angiographic images that allows for 3D display of coronary structures. The purpose of this study was to validate our 3DR algorithm and quantify anatomic characteristics of the right coronary artery (RCA) in vivo. METHODS: Accuracy and reproducibility studies were performed using 3DRs of a coronary phantom and in vivo following 3DRs in 40 patients. The anatomic features of the RCA were then quantified in 100 patients. RESULTS: Comparison of length and bifurcation angles (BA) from the phantom to the 3DRs revealed good accuracy and correlation for both (r = 0.95 and 0.93 respectively), with diameter error of < 7%. In vivo, the average root mean square (RMS) error in the spatial coordinates of the vessel centerlines was 3.12 +/- 0.77 and 3.16 +/- 0.75 mm in 20 left coronary arteries (LCA) and 20 RCAs respectively. Interobserver average RMS error was 3.47 +/- 1.96 mm and intraobserver average RMS error was 3.02 +/- 1.07 and 3.44 +/- 1.57 mm for two different operators (p = NS). The average RCA length was 10.2 +/- 1.7 cm, average radius of curvature (ROC) was 52 +/- 9 degrees, and the average 3D bifurcation angle of the posterior descending artery (PDA) from the RCA was 55 +/- 22 degrees. Foreshortening (FS) of the segments of the RCA in three 'standard' projections ranged from 0-60, 0-75, and 0-82% respectively. CONCLUSIONS: Using our 3DR algorithm patient-specific anatomic characteristics can be accurately displayed and quantified, expanding the information that can be derived from routine coronary angiography.

Restraining orders: a frequent marker of adverse maternal health.

OBJECTIVE: Women with histories of interpersonal violence are poorly identified because of barriers in self-disclosure. This study identified differences on maternal health and child behavior between women who report filing a restraining order (RO) and those who do not among a nonreferred sample of women living in high-crime neighborhoods. METHODS: During a maternal interview mothers were asked whether they ever filed a RO, the victim/defendant relationship, the number of times, and the year of the filing. Four types of violence were coded independently based on maternal narratives: verbal harassment, verbal threats or intimidation, physical assault, and destruction of property. We controlled for differences between RO and non-RO groups regarding demographic background, partner characteristics, other types of maternal past victimization, and use of alcohol and illicit drugs. Outcomes for mothers include partner aggression (Conflict Tactics Scale-R), perception of health and bodily pain (SF-36 Health Survey), distress symptoms (SCL90-R), posttraumatic stress (PTS)-related symptoms, and partial posttraumatic stress disorder (PTSD) diagnosis (modified Diagnostic Interview Schedule PTSD-Module). Outcomes for the child include partner aggression (Conflict Tactic Scale-R), behavior problems (CBC 2-3 or Child Behavior Checklist), and PTS-related symptoms (PTS-related symptom checklist). PATIENTS: One hundred sixty patients between 3.0 to 6.1 years who resided within five residential ZIP codes with a high rate of local crime in the City of Boston were drawn from a pediatric care clinic practice. Patients were participants of a larger study about the impact of community violence on mother-child relations. RESULTS: Sixty-four (40%) of 160 mothers reported a history of filing a RO against a current boyfriend or husband (39%), ex-boyfriend or husband (44%), someone known (8%), or other (9%), with a mean of 3.9 years (standard deviation = 3.5 years) since RO filing. After controlling for covariates of marital status, immigrant status, public assistance, and lifetime sexual victimization, we found a significant multivariate analysis of covariance group effect on maternal outcomes. Analysis of covariance analyses indicated that mothers in the RO group experienced higher current partner verbal aggression and physical violence to mother, poorer health, and higher PTS-related symptoms, compared with mothers in the non-RO group. More mothers in the RO group met partial lifetime PTSD diagnosis. Unadjusted for maternal covariates, the multivariate analysis of variance analyses on child outcomes (partner aggression to child, behavior problems, and PTS-related symptoms) indicated a nonsignificant group effect. CONCLUSIONS: Among dyads residing in high-risk crime areas, the incidence of RO histories is substantive considering this was a nonshelter, nonreferred sample. The inquiry about the history of a RO may provide a new and efficient marker to quality of current partner relationship, maternal health, and maternal stress-related symptomatology.

Continuous infusion of epoprostenol improves the net balance between pulmonary endothelin-1 clearance and release in primary pulmonary hypertension.

BACKGROUND: Primary pulmonary hypertension results from progressive narrowing of the precapillary pulmonary vasculature. A variety of endothelial abnormalities have been identified, including a net reduction in pulmonary clearance of the vasoconstrictor and smooth muscle mitogen endothelin-1. In many patients, net pulmonary release of endothelin-1 is observed. Chronic infusions of epoprostenol (prostacyclin) improve functional capacity, survival, and hemodynamics in patients with advanced primary pulmonary hypertension. We hypothesized that the epoprostenol infusions, as compared with conventional therapy, might alter the abnormal pulmonary endothelin-1 homeostasis. METHODS AND RESULTS: Using a subset of patients from a larger randomized study comparing epoprostenol plus conventional therapy (n=11 in the present study) with conventional therapy alone (n=7 in the present study), we determined the ratio of plasma endothelin-1 levels in systemic arterial blood leaving the lung to levels in mixed venous blood entering the lung both before randomization and after 88 days of continuous therapy. There were no differences between the 2 groups before therapy, but by day 88, the epoprostenol-treated group had a greater proportion of patients (82%) with an arterial/venous ratio <1 than did the conventional therapy group, in which only 29% of patients had a ratio <1 (P<0.05). CONCLUSIONS: These results suggest that continuous epoprostenol therapy may have a beneficial effect on the balance between endothelin-1 clearance and release in many patients with primary pulmonary hypertension and may provide one explanation for the salutary effect of epoprostenol in this disease.

Mental health services for children who witness domestic violence.

Exposure to domestic violence has significant negative repercussions for children's social, emotional, and academic functioning. In the past decade, mental health professionals have developed treatment programs and approaches aimed at mitigating these deleterious effects. Their efforts, however, are often hampered by difficulty identifying and gaining access to the target population because the occurrence of domestic violence remains a family secret in many households. Clinicians and researchers have published descriptions of group and individual therapy approaches for children who witness domestic violence. These approaches share several goals: promoting open discussion about children's experiences with domestic violence, helping children to deal with the emotions and consequences that follow such exposure, reducing the problematic symptoms children experience, strengthening children's relationships with their nonabusive caregivers, and helping children and their families to create and maintain relationships and living situations that are free from violence and abuse. One limitation of the literature describing these interventions is the absence of controlled outcome studies demonstrating the effects of these programs, in the short and long terms. Thus, development of such evaluative components is an important future direction for this field. Some of the other challenges that confront clinicians include working with children's families, addressing children's complex and intense emotional experiences, and determining whether children have themselves been victims of abuse or neglect (and then interfacing with child protective services).

Changes in gene expression in the intact human heart. Downregulation of alpha-myosin heavy chain in hypertrophied, failing ventricular myocardium.

Using quantitative RT-PCR in RNA from right ventricular (RV) endomyocardial biopsies from intact nonfailing hearts, and subjects with moderate RV failure from primary pulmonary hypertension (PPH) or idiopathic dilated cardiomyopathy (IDC), we measured expression of genes involved in regulation of contractility or hypertrophy. Gene expression was also assessed in LV (left ventricular) and RV free wall and RV endomyocardium of hearts from end-stage IDC subjects undergoing heart transplantation or from nonfailing donors. In intact failing hearts, downregulation of beta1-receptor mRNA and protein, upregulation of atrial natriuretic peptide mRNA expression, and increased myocyte diameter indicated similar degrees of failure and hypertrophy in the IDC and PPH phenotypes. The only molecular phenotypic difference between PPH and IDC RVs was upregulation of beta2-receptor gene expression in PPH but not IDC. The major new findings were that (a) both nonfailing intact and explanted human ventricular myocardium expressed substantial amounts of alpha-myosin heavy chain mRNA (alpha-MHC, 23-34% of total), and (b) in heart failure alpha-MHC was downregulated (by 67-84%) and beta-MHC gene expression was upregulated. We conclude that at the mRNA level nonfailing human heart expresses substantial alpha-MHC. In myocardial failure this alteration in gene expression of MHC isoforms, if translated into protein expression, would decrease myosin ATPase enzyme velocity and slow speed of contraction.

Pyrogenic reactions in patients undergoing cardiac catheterization associated with contaminated glass medicine cups.

Pyrogenic reactions are potentially life-threatening complications caused by bacterial endotoxin. After two cardiac catheterization patients developed rigors the same day, the procedures were halted and a case control study was conducted. To identify case patients (persons with rigors < or = 3 hr after catheterization during September 25-November 9, 1995), we reviewed medical records of all cardiac catheterization patients who had a blood culture or received intravenous meperidine. Twelve case patients and 40 randomly selected control patients were identified. No specific catheter was associated with case patients, but exposure to intracoronary-nitroglycerin (NTG) was (odds ratio = 12.0; 95% confidence interval 2.2, 75.6). NTG or indocyanine green dye was poured into glass medicine cups previously washed in an enzyme cleaner and then sterilized. The cleaner, used for an entire day, had elevated levels of gram-negative bacteria (> 10(4) colony forming units/mL) and endotoxin (434 endotoxin units [EU]/mL]); the reprocessed cups had no live bacteria but had elevated endotoxin levels (median 2,250 EU). Exposure to contaminated glass medicine cups probably resulted in pyrogenic reactions and contributed to death in two critically ill patients.

Effects of long-term infusion of prostacyclin (epoprostenol) on echocardiographic measures of right ventricular structure and function in primary pulmonary hypertension. Primary Pulmonary Hypertension Study Group.

BACKGROUND: Right heart failure is an important cause of morbidity and mortality in primary pulmonary hypertension. In a recent prospective, randomized study of severely symptomatic patients, treatment with prostacyclin (epoprostenol) produced improvements in hemodynamics, quality of life, and survival. This article describes the echocardiographic characteristics of participants in this trial; the relationship of echocardiographic variables to hemodynamic parameters, exercise capacity, and quality of life; and the echocardiographic changes associated with prostacyclin therapy. METHODS AND RESULTS: The 81 patients enrolled in this multicenter trial were randomized to treatment with a long-term infusion of prostacyclin in addition to conventional therapy (n = 41) or conventional therapy alone (n = 40) for 12 weeks. Echocardiograms and assessments of hemodynamics, exercise capacity, and quality of life were performed before and after the treatment phase. On baseline evaluation, patients had marked right ventricular dilatation and dysfunction, abnormal septal curvature, and significant tricuspid regurgitation with a high regurgitant velocity. Pericardial effusions were common. More pronounced abnormalities in right heart structure and function were associated with higher pulmonary arterial and mean right atrial pressures, lower cardiac index, and impaired exercise capacity but had no predictable relationship to quality-of-life indicators. The 12-week infusion of prostacyclin had beneficial effects on right ventricular size, curvature of the interventricular septum, and maximal tricuspid regurgitant jet velocity. CONCLUSIONS: The echocardiographic manifestations of severe primary pulmonary hypertension reflect abnormalities in hemodynamics and exercise capacity. Prostacyclin has beneficial effects on right heart structure and function that may contribute to the clinical improvement and prolonged survival observed with this drug.

Automated determination of left ventricular volume curves from bi-plane digital angiography without explicit use of edge detection algorithms.

Automated computation of left ventricular (LV) global and regional function using contrast angiography has not yet become a routine procedure with the advent of digital cardiac imaging systems. We describe a new technique to compute LV volume curves which does not require the use of manual or semi-automated detection of endocardial borders and provides on-line implementation of volumetric curves and computation of pressure volume loops during catheterization. The approach uses the concepts of variable entropy (or information) of left ventricular images throughout the cardiac cycle. LV volume curves are computed with an interpolation scheme using those LV volume curves of a patient data base which are associated with the closest variation in entropy in the RAO projection to the analyzed patient data according to a simple metric. Computed LV volume curves were correlated with those obtained with manual tracing. Left ventricular ejection fraction (LVEF), time to end systole (TES) and angiographic cardiac output (CO) were compared to those obtained with the manual method. Results using a data base of 365 patients revealed excellent correlation (r = 0.97) between manually derived volume curves and volume curves computed with the automated technique within a large range of LVEFs. In 87% of all cases the computed LVEF values were found within +/- 10% of the value obtained with the gold standard method. The systolic phase of the volume curves showed that 81% of all cases had the same accuracy. The TES showed much more variation due to undersampling of the cardiac cycle in time (r = 0.71).

Pulmonary hypertension in chronic liver disease.

Pulmonary hypertension develops in approximately 2% of patients with portal hypertension. Diagnosis is often difficult and requires a high degree of clinical suspicion. Treatment of patients with portal and pulmonary hypertension is limited, and mean survival following diagnosis is approximately 15 months. The effect of liver transplantation on the natural history of disease is discussed.

A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension.

BACKGROUND: Primary pulmonary hypertension is a progressive disease for which no treatment has been shown in a prospective, randomized trial to improve survival. METHODS: We conducted a 12-week prospective, randomized, multicenter open trial comparing the effects of the continuous intravenous infusion of epoprostenol (formerly called prostacyclin) plus conventional therapy with those of conventional therapy alone in 81 patients with severe primary pulmonary hypertension (New York Heart Association functional class III or IV). RESULTS: Exercise capacity was improved in the 41 patients treated with epoprostenol (median distance walked in six minutes, 362 m at 12 weeks vs. 315 m at base line), but it decreased in the 40 patients treated with conventional therapy alone (204 m at 12 weeks vs. 270 m at base line; P < 0.002 for the comparison of the treatment groups). Indexes of the quality of life were improved only in the epoprostenol group (P < 0.01). Hemodynamics improved at 12 weeks in the epoprostenol-treated patients. The changes in mean pulmonary-artery pressure for the epoprostenol and control groups were -8 percent and +3 percent, respectively (difference in mean change, -6.7 mm Hg; 95 percent confidence interval, -10.7 to -2.6 mm Hg; P < 0.002), and the mean changes in pulmonary vascular resistance for the epoprostenol and control groups were -21 percent and +9 percent, respectively (difference in mean change, -4.9 mm Hg/liter/min; 95 percent confidence interval, -7.6 to -2.3 mm Hg/liter/min; P < 0.001). Eight patients died during the study, all of whom had been randomly assigned to conventional therapy (P = 0.003). Serious complications included four episodes of catheter-related sepsis and one thrombotic event. CONCLUSIONS: As compared with conventional therapy, the continuous intravenous infusion of epoprostenol produced symptomatic and hemodynamic improvement, as well as improved survival in patients with severe primary pulmonary hypertension.

Smaller alveolar-arterial O2 gradients in Tibetan than Han residents of Lhasa (3658 m).

Previous studies have indicated that native Tibetans have a larger lung capacity and better maintain arterial O2 saturation during exercise than Han ("Chinese") acclimatized lowlanders. To test if differences in ventilation or alveolar-arterial O2 gradient (A-aDO2) were responsible, we compared 10 lifelong Tibetan and 9 Han acclimatized newcomer residents of Lhasa (3658 m) at rest and during progressive exercise. Resting blood gas tensions and arterial O2 saturation in the two groups were similar. During exercise the Tibetans had lower total ventilation and higher arterial CO2 tensions than the Han (both P < 0.01) and markedly lower A-aDO2 (7 +/- 1 vs. 11 +/- 1, 13 +/- 1 vs. 18 +/- 1, and 14 +/- 1 vs. 20 +/- 1 mmHg at light, medium, and heavy workloads respectively, all P < 0.01). The Tibetans' narrower A-aDO2 compensated for their lower exercise ventilation such that arterial O2 tension and saturation were raised above acclimatized newcomer values and better maintained during exercise. We concluded that the Tibetans exhibited more efficient pulmonary gas exchange which compensated for reduced ventilation and lessened respiratory effort.

Angiotensin II formation in the intact human heart. Predominance of the angiotensin-converting enzyme pathway.

It has been proposed that the contribution of myocardial tissue angiotensin converting enzyme (ACE) to angiotensin II (Ang II) formation in the human heart is low compared with non-ACE pathways. However, little is known about the actual in vivo contribution of these pathways to Ang II formation in the human heart. To examine angiotensin II formation in the intact human heart, we administered intracoronary 123I-labeled angiotensin I (Ang I) with and without intracoronary enalaprilat to orthotopic heart transplant recipients. The fractional conversion of Ang I to Ang II, calculated after separation of angiotensin peptides by HPLC, was 0.415 +/- 0.104 (n = 5, mean +/- SD). Enalaprilat reduced fractional conversion by 89%, to a value of 0.044 +/- 0.053 (n = 4, P = 0.002). In a separate study of explanted hearts, a newly developed in vitro Ang II-forming assay was used to examine cardiac tissue ACE activity independent of circulating components. ACE activity in solubilized left ventricular membrane preparations from failing hearts was 49.6 +/- 5.3 fmol 125I-Ang II formed per minute per milligram of protein (n = 8, +/- SE), and 35.9 +/- 4.8 fmol/min/mg from nonfailing human hearts (n = 7, P = 0.08). In the presence of 1 microM enalaprilat, ACE activity was reduced by 85%, to 7.3 +/- 1.4 fmol/min/mg in the failing group and to 4.6 +/- 1.3 fmol/min/mg in the nonfailing group (P < 0.001). We conclude that the predominant pathway for angiotensin II formation in the human heart is through ACE.