Identification of patients at high risk for death and cardiac ischemic events after hospital discharge

Background Patients with unstable angina (UA) and non-ST-elevation myocardial infarction (NSTEMI) remain at risk for death and cardiac ischemic events after being discharged from the hospital. Methods We examined whether the Thrombolysis In Myocardial Infarction (TIMI) risk score for UA/NSTEMI, ascertained at presentation in patients enrolled in the TIMI 11B and Efficacy and Safety of Subcutaneous Enoxaparin in Unstable Angina and Non-Q-Wave MI (ESSENCE) trials, could be used to identify patients at high risk for major cardiac events after hospital discharge. Results There were a total of 1218 major cardiac events, defined as death, nonfatal myocardial infarction, or urgent revascularization, by day 43. Of these events, 336 (28%) occurred in patients after they were discharged from the hospital. Use of the TIMI risk score for UA/NSTEMI revealed a progressive, statistically significant increase in the rate of events after leaving the hospital as the patients' baseline level of risk increased (P < .001 for χ² test for trend). For patients with a risk score of 5 to 7, treatment with enoxaparin during the acute phase was associated with an odds ratio of 0.51 (95% CI 0.29-0.91) for the occurrence of death and cardiac ischemic events after hospital discharge. Conclusions More than one fourth of the major cardiac events that will occur in the first 6 weeks occur after discharge from the hospital. Stratification at presentation on the basis of the TIMI risk score for UA/NSTEMI can be used to identify patients at high risk for these events. Among patients at high-risk, acute-phase treatment with enoxaparin significantly reduces the risk of major cardiac events after leaving the hospital. (Am Heart J 2002;143:966-70.)     

The SYNERGY trial: study design and rationale

Background Enoxaparin was shown to be superior to unfractionated heparin in the patients with non-ST-segment elevation acute coronary syndromes (ACS) in the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events study and the Thrombolysis In Myocardial Infarction (TIMI) 11B trial. However, enoxaparin has had limited acceptance in clinical practice, in part because of the contemporary management of these patients, which includes glycoprotein IIb/IIIa inhibition and the use of early invasive management strategies. Study Design The Superior Yield of the New strategy of Enoxaparin, Revascularization and GlYcoprotein IIb/IIIa inhibitors (SYNERGY) trial is an 8000-patient, prospective, randomized, open-label, multicenter investigation of enoxaparin compared with unfractionated heparin in patients at high risk with non-ST-segment elevation ACS treated with an early invasive strategy. The primary efficacy end point is death or nonfatal myocardial infarction 30 days after enrollment. Implications The SYNERGY trial is the largest study currently planned for the acute therapy of patients with non-ST-segment elevation ACS and the first large trial since the publication of the revised American College of Cardiology/American Heart Association guidelines for the management of these patients. In addition to evaluating the potential superiority of enoxaparin over unfractionated heparin, this investigation will provide important observations of current treatment strategies in patients with ACS. (Am Heart J 2002;143:952-60.)     

Serum glucose and lipid levels in adult congenital heart disease patients

Atherosclerosis has been correlated with known cardiovascular risk factors such as serum glucose or lipid levels. Because congenital heart disease patients tend to survive until adulthood, atherosclerosis has also become a matter of concern in these patients. One hundred fifty-eight congenital heart disease patients and 152 patients selected at random from the population were studied and compared to determine serum glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, and triglycerides levels. Both groups had similar socioeconomic status levels and the same environmental influences. Significant differences were seen between congenital heart disease patients and the control group, after sex, age, and body mass index adjustment, in fasting plasma glucose (97.7 [94.2-101.2] vs 86.9 [83.2-90.7], P < .001), total cholesterol (171.5 [165.7-177.3] vs 199.8 [90.7-206.0], P < .001), LDL cholesterol (103.9 [98.8-108.8] vs 123.8 [118.5-129.1], P < .001), and high-density lipoprotein cholesterol (48.1 [46.2-50.0] vs 54.2 [52.1-56.2], P < .001) levels. Nonsignificant differences were seen in triglycerides concentrations. Those patients with ventricular septal defect, coarctation of the aorta, and cyanosis had the lowest total cholesterol and LDL cholesterol concentrations. Congenital heart disease patients have lower plasma cholesterol concentrations and higher serum glucose levels than noncongenital ones.     

Evaluation of platelets in heart failure: is platelet activity related to etiology,functional class,or clinical outcomes?

Objectives We sought to determine whether platelet activity in patients with heart failure is related to an ischemic versus nonischemic etiologic condition, clinical disease severity, or adverse clinical outcomes. Background Platelet activity may affect outcome in patients with heart failure. A prospective evaluation of the relation of baseline platelet function to etiologic condition, New York Heart Association (NYHA) class, and clinical outcomes has not been previously reported. Methods Ninety-six consecutive outpatients with ambulatory heart failure with an ejection fraction <0.40 and NYHA Class II to IV symptoms who presented to the Duke Heart Failure Clinic and 14 healthy control subjects formed the study groups. Baseline characteristics and blood analyzed for thromboxane (Tx) B₂, 6-keto PGF_1α, platelet contractile force, adenosine diphosphate/collagen shear-induced closure time, whole blood aggregation and CD41, CD31, CD62p, and CD51/CD61 by flow cytometry were determined. Survival status and hospitalizations were determined in the heart failure patient cohort. Results The median age of patients was 65 years (22% female, 64% white). An ischemic etiologic condition was present in 61% of patients. The population had mild to moderate heart failure: NYHA class I (1%), II (41%), III (46%), and IV (12.5%) and severe ventricular dysfunction (median ejection fraction = 0.20). There were 39 clinical events (7 deaths, 3 cardiac transplants, 29 other first hospitalizations) in 305 median days of observation. Platelet activity, indicated by whole blood aggregation with 5 μmol adenosine diphosphate (P = .04) and Tx B₂ (P = .01), was higher in patients with heart failure. Whole blood aggregation was greater than the 90th percentile in 22% of patients with heart failure versus 7% of control subjects. Platelet function did not differ for any of the markers between the ischemic and nonischemic groups and was not affected by antecedent aspirin. There was no relation of NYHA class or the occurrence of events to platelet activity. Conclusion Platelet activity is heightened in 22% of outpatients with stable heart failure symptoms and is not affected by antecedent aspirin therapy. The degree of platelet activation is similar in ischemic and nonischemic patients with heart failure and is not related to clinical disease severity. Current methods to assess platelet activation do not appear to predict outcome. (Am Heart J 2002;143:1068-75.)     

Long-term outcome and the use of revascularization in patients with heart failure,suspected ischemic heart disease,and large reversible myocardial perfusion defects

Background The potential role of coronary revascularization in the management of patients with congestive heart failure and suspected ischemic heart disease remains to be defined. Myocardial perfusion imaging can identify patients with ischemic heart disease as the etiology for left ventricular dysfunction who might benefit from revascularization. Methods We retrospectively identified heart failure patients with suspected ischemic heart disease who had large reversible perfusion defects to determine their long-term outcome and rate of revascularization. The study group consisted of 77 patients with congestive heart failure, left ventricular ejection fraction <45%, and suspected ischemic heart disease who underwent myocardial perfusion imaging during the period of January 1, 1991, to December 31, 1997, and had large reversible perfusion defects. Results The 5-year mortality rate was 57.6%. The revascularization rate was only 13% for 5 years of follow-up. The number of patients undergoing revascularization was too small to assess its impact on outcome. Conclusion These results indicate a high 5-year mortality rate and a low utilization of coronary revascularization in patients with heart failure and large reversible perfusion defects. The low rate of revascularization reflects at least in part the absence of the generalizability of the existing literature to the optimal means of treating patients with heart failure and myocardial ischemia and points to the need for a randomized clinical trial. (Am Heart J 2002;143:904-9.)     

Safety and efficacy of unfractionated heparin versus enoxaparin in patients who are obese and patients with severe renal impairment: analysis from the ESSENCE and TIMI 11B studies

Background

The advantages of enoxaparin over unfractionated heparin (UFH) for the treatment of patients with non-ST-segment elevation acute coronary syndromes are well established. However, no data are available about the safety and efficacy in patients who are obese and patients with severe renal impairment.

Methods

A retrospective analysis of treatment effects was performed on patients who were obese and patients with severe renal impairment from the Efficacy Safety Subcutaenous Enoxaparin in Non-Q-wave Coronary Events (ESSENCE) and Thrombolysis in Myocardial Infarction (TIMI) 11B trials, in which patients were treated with enoxaparin or UFH. The primary composite end point was death, myocardial infarction (MI), and urgent revascularization (UR), and the secondary end points were major and any hemorrhage.

Results

When compared with UFH, enoxaparin reduced the rate of the primary end point in patients who were obese (14.3% vs 18.0%, P = .05), patients who were not obese (16.1% vs 19.2%, P <.01), and patients without severe renal impairment (15.7% vs 18.4%, P <.01). There was no significant difference in major bleeding between enoxaparin and UFH in any of the 4 subgroups. There were no differences in either the primary end point (17.6% vs 16.2%, P = .39) or major hemorrhage (1.3% vs 0.8%, P = .12) in patients who were obese receiving either UFH or enoxaparin compared with patients who were not obese. Patients with severe renal impairment tended toward a higher rate of the primary end point (25.9% vs 17%, P = .09) and experienced more major hemorrhages (6.6% vs 1.1%, P <.0001).

Conclusions

Enoxaparin reduced the rate of the combined end point of death/MI/UR in the subgroups of patients who were obese, patients who were not obese, and patients without renal insufficiency. Obesity did not impact clinical outcomes in the combined analysis of ESSENCE and TIMI 11B. Patients with severe renal impairment have a higher risk of clinical events and major and any hemorrhages than patients without severe renal impairment, whether they are treated with UFH or enoxaparin.     

Cardiac troponin I: a potential marker of exercise intolerance in patients with moderate heart failure

Background In severe heart failure, increased values of cardiac troponins have been detected during decompensation. In this study, we investigated whether an increase of cardiac troponin I can be observed after symptom-limited exercise and after an exercise training session in patients with moderate heart failure. Methods Twenty-seven patients with moderate heart failure (New York Heart Association II-III, ejection fraction 31% ± 8%) were compared with 9 patients with mild heart failure and 10 subjects without heart failure. They underwent a symptom-limited exercise test and a bicycle exercise training session at >80% of maximal heart rate over 20 to 30 minutes. Plasma cTnI levels were measured at baseline, after symptom-limited exercise (hourly for 5 hours), and after training (4 and 10 hours). Results Patients with moderate heart failure showed an increase of cTnI from 37 ± 49 pg/mL to 73 ± 59 pg/mL (P < .001) after symptom-limited exercise. Four patients with moderate and 1 with mild heart failure and normal cTnI values at rest showed an increase of cTnI above 100 pg/mL after acute exercise but not after training. Subjects without heart failure had lower cTnI levels at rest and significantly lower values after symptom-limited exercise and training (P < .05 for each). Conclusion Patients with symptomatic heart failure reveal an increase of cTnI after symptom-limited exercise at levels that indicate minor myocardial damage. The prognostic impact of this finding should, therefore, be further investigated. (Am Heart J 2002;144:351-8)     

Bisoprolol for the treatment of chronic heart failure: a meta-analysis on individual data of two placebo-controlled studies--CIBIS and CIBIS II. Cardiac Insufficiency Bisoprolol Study

Background Despite the available evidence from randomized clinical trials, β-blockers are often not used optimally in patients with congestive heart failure (CHF). This meta-analysis aims at providing a precise and quantitative estimate of the benefit and risks of long-term bisoprolol on major clinical events in patients with CHF, both overall and in selected subgroups. This may help clinicians in their decisions as to whether to prescribe bisoprolol for their individual patients. Methods Meta-analysis was performed of results from the 2 randomized, controlled clinical studies in which bisoprolol was compared with placebo (Cardiac Insufficiency Bisoprolol Study [CIBIS and CIBIS II]), which included 3288 patients with proven CHF. The main outcomes were total death, cardiovascular death, sudden death, hospitalization for heart failure, and myocardial infarction. Results A highly significant 29.3% relative reduction of death (17%, 40%; P = .00003) was observed, as well as significant risk reduction in cardiovascular death and sudden death in favor of bisoprolol. Also, a highly significant relative reduction of 18.4% (25%, 11%; P = .00001) in hospital admission or death was observed. A similar relative reduction of death was consistently observed in selected subgroups of patients. Conclusions Bisoprolol prevents major cardiovascular events in patients with CHF with a high benefit-to-risk ratio and can be recommended for these patients. (Am Heart J 2002;143:301-7.)     

Enoxaparin in acute coronary syndromes: evidence for superiority over placebo or untreated control

Background Heparins, both standard unfractionated heparin (SUFH) and low-molecular weight heparin, play a prominent role in the treatment of acute coronary syndromes. Enoxaparin has been shown in 2 trials to be superior to heparin but has not been compared with placebo or untreated control. Methods A putative enoxaparin versus placebo/control odds ratio (OR) was computed with a recently described statistical technique with the logarithm of the ORs of the pooled results of both the enoxaparin-SUFH trials and SUFH-placebo or controlled trials. Results The combined heparin versus control results show a 33% reduction in the risk of death or acute myocardial infarction (AMI), with an OR of 0.67 (95% confidence interval [CI], 0.45 to 0.99). At up to 12 weeks (data from only 4 trials), the combined results show a 21% reduction (OR, 0.79; 95% CI, 0.54 to 1.15; P = .23). The 2 enoxaparin trials show a nonsignificant 20% reduction in the risk of death or AMI during treatment (OR, 0.80; 95% CI, 0.68 to 1.16; P = .24) and a significant reduction at 43 days (OR, 0.82; 95% CI, 0.69 to 0.97; P = .022). With these pooled data, the putative OR for enoxaparin versus placebo/untreated control during treatment is 0.53 (95% CI, 0.31 to 0.92; P = .023). The data are consistent with a 47% reduction in the risk of death or AMI. The difference persists on longer term follow-up period (OR, 0.65; 95% CI, 0.43 to 0.98; P = .04). The risk of bleeding is nonsignificantly increased (OR, 2.32; 95% CI, 0.8 to 7.85; P = .51). Conclusion On the basis of this methodology, enoxaparin would appear to be more effective than placebo when added to aspirin in acute coronary syndromes. Moreover, the effect of enoxaparin is similar to the results of a metaanalysis of trials of other low-molecular weight heparins versus placebo/control. (Am Heart J 2002;143:748-52.)     

Effect of pravastatin on cardiovascular events and mortality in 1516 women with coronary heart disease: results from the Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) study

Background The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) study showed that cholesterol-lowering therapy prevented further events in patients with coronary heart disease and average cholesterol levels. The aim of this subgroup analysis was to assess the effects of pravastatin in women. Methods A total of 1516 women (756 assigned to take pravastatin) in a cohort of 9014 patients with previous myocardial infarction or unstable angina and a baseline plasma cholesterol level of 4.0 to 7.0 mmol/L (155-271 mg/dL) were assigned to receive pravastatin (40 mg/d) or placebo. Major cardiovascular disease events in 6 years were measured. Results Women were at a lesser risk than men for death from any cause (10.3% vs 14.8%, P < .01), death from coronary heart disease (6.6% vs 8.6%, P = .04), and coronary revascularization (13.6% vs 16.2%, P = .05) and at a similar risk of myocardial infarction (9.2% vs 10.5%, P = .26), stroke (3.6% vs 4.7%, P =.11), and hospitalization for unstable angina (25.1% vs 24.5%, P = 0.90). Pravastatin significantly reduced the risk of all prespecified cardiovascular events in all LIPID patients. Relative treatment effects in women did not differ significantly from those in men (P > .05) for any events except hospitalization for unstable angina. There were too few events to demonstrate separately significant effects in women; the estimated relative risk reduction with pravastatin was 11% (95% CI -18%-33%) for coronary heart disease death or nonfatal myocardial infarction, 18% (95% CI -25%-46%) for coronary heart disease death, 16% (95% CI -19%-41%) for myocardial infarction, and 17% (95% CI -2%-33%) for coronary heart disease death, myocardial infarction, or coronary revascularization. Conclusions The study had the largest secondary-prevention female cohort studied thus far, but was not adequately powered to show separate effects in women. Nevertheless, the results were consistent with the main results of this and other trials in showing reduced risks with cholesterol-lowering treatment. (Am Heart J 2003;145:643-51.)     

Elevated serum creatinine is associated with 1-year mortality after acute myocardial infarction

Background Cardiovascular mortality is high in individuals with end-stage renal disease. However, less is known about the prognostic importance of moderate renal insufficiency in patients with acute myocardial infarction. Methods We studied all patients with acute myocardial infarction admitted through the emergency department to an urban, academic hospital over 1 year. Patients were classified as having elevated (>133 μmol/L [1.5 mg/dL]) or normal (≤133 μmol/L) serum creatinine at presentation. Results Of 483 patients, 22% had elevated creatinine and 78% had normal creatinine. By 1 year, 46% of patients with elevated creatinine and 15% of patients with normal creatinine had died (P < .001). The unadjusted hazard ratio for 1-year mortality was increased in patients with elevated creatinine compared with those with normal creatinine (hazard ratio 3.85, 95% CI 2.61-5.67). After adjustment for baseline characteristics and treatment, the multivariable-adjusted hazard ratio for 1-year mortality remained increased in patients with elevated creatinine compared with those with normal creatinine (hazard ratio 2.40, 95% CI 1.55-3.72). There was an important modification of the prognostic value of creatinine by the presence of congestive heart failure at presentation (P value for interaction = .04). The adjusted hazard ratio for 1-year death associated with elevated creatinine compared with normal creatinine was 3.89 (95% CI 1.87-8.07) in patients without congestive heart failure and 1.92 (95% CI 1.10-3.36) in patients with congestive heart failure. Conclusions Elevated serum creatinine at presentation is associated with 1-year mortality after acute myocardial infarction. Further study is needed to optimize treatment after myocardial infarction in this high-risk group. (Am Heart J 2002;144:1003-1011.)     

A comparison of the Framingham and European Society of Cardiology coronary heart disease risk prediction models in the normative aging study

Background A number of prediction models have been developed in an attempt to accurately identify patients at increased risk of a first coronary heart disease event. We sought to determine the ten-year incidence of coronary heart disease events in a healthy cohort with measurable risk factors, and to compare these results with the predicted number of events by use of both the Framingham and European Society of Cardiology risk prediction models. Methods We compared the predicted and observed number of events in 5 risk categories in 1393 subjects aged 30 to 74 years who were enrolled in the Normative Aging Study. Results The risk prediction models reliably stratify populations with regards to relative risk of coronary heart disease events and there is reasonable agreement between the 2 models (weighted κ = 0.46, P < .01). The Framingham model underestimated the absolute risk of coronary heart disease events in the low-risk group, and both risk prediction models overestimated the absolute risk of events in the high- or very-high-risk groups (Framingham c-statistic = 0.60, European Society of Cardiology c-statistic = 0.58). Conclusions Despite simplification, the accuracy of the European model was not significantly different from the Framingham model. But the accuracy of absolute risk prediction, particularly at the extremes of risk, is imperfect. Refinement and validation of these risk prediction models is important because they affect the management of individual patients and the allocation of community resources. (Am Heart J 2002;144:95-100.)     

Efficacy and safety of crataegus extract WS 1442 in comparison with placebo in patients with chronic stable New York Heart Association class-III heart failure

Objective The purpose of this study was to investigate whether long-term therapy with crataegus extract WS 1442 is efficacious as add-on therapy to preexisting diuretic treatment in patients with heart failure with a more advanced stage of the disease (New York Heart Association [NYHA] class III), whether effects are dose dependent, and whether the treatment is safe and well tolerated. Methods Exercise capacity was assessed by use of seated bicycle ergometry with incremental workloads. Scores for subjective symptoms and complaints made by the patients were analyzed. Efficacy and tolerability of the treatments were judged by both the patients and investigators. Safety was assessed by the documentation of adverse events and the safety laboratory. Results A total of 209 patients were randomized to treatment with 1800 mg of WS 1442, 900 mg of WS 1442, or with placebo. After 16 weeks of therapy with 1800 mg of WS 1442 per day, maximal tolerated workload during bicycle exercise showed a statistically significant increase in comparison with both placebo and 900 mg of WS 1442. Typical heart failure symptoms as rated by the patients were reduced to a greater extent by WS 1442 than by placebo. This difference was significant for both doses of WS 1442. Both efficacy and tolerability were rated best for the 1800 mg of WS 1442 group by patients and investigators alike. The incidence of adverse events was lowest in the 1800 mg of WS 1442 group, particularly with respect to dizziness and vertigo. Conclusions The data from this study confirm that there is a dose-dependent effect of WS 1442 on the exercise capacity of patients with heart failure and on typical heart failure-related clinical signs and symptoms. The drug was shown to be well tolerated and safe. (Am Heart J 2002;143:910-5.)     

Vasopeptidase inhibitor reduces inhospital costs for patients with congestive heart failure: results from the IMPRESS trial. Inhibition of Metallo Protease by BMS-186716 in a Randomized Exercise and Symptoms Study in Subjects With Heart Failure

Background The Inhibition of Metallo Protease by BMS-186716 in a Randomized Exercise and Symptoms Study in Subjects With Heart Failure (IMPRESS) clinical trial randomized patients with congestive heart failure to a daily regimen of either omapatrilat or lisinopril. At 24 weeks, patients randomized to omapatrilat had a significant reduction in the combined end point of death, hospitalization, or discontinuation of study drug for worsening heart failure when compared with patients randomized to lisinopril. They also had significantly fewer serious cardiac adverse events. Objective This study sought to determine the economic consequences of the lower event rates of patients who were given omapatrilat. Methods Economic outcomes (major hospitalizations and their associated medical costs) were compared between treatment groups and assessed by use of the societal perspective. Hospitalization information was obtained from the IMPRESS trial's standardized case report and serious adverse event forms. Hospital costs were evaluated by means of assigning each hospital admission a diagnosis-related group and an average cost for physician and hospital services. Emergency department visits were included only when they were made for worsening heart failure and were assigned costs equivalent to the average hospital and physician Medicare reimbursement for these visits in Duke University Medical Center's heart failure program. Drug costs were not assessed. Results Although the typical patient in both treatment groups was event-free, there was a trend toward a greater number of hospitalizations in the patients given lisinopril than in the patients given omapatrilat (P = .07). Differences in the distribution of cardiac hospitalizations between patients given lisinopril and patients given omapatrilat were significant (P = .03). There was a trend toward lower medical costs at 24 weeks in patients given omapatrilat versus patients given lisinopril ($1930 vs $2002, P = .09). Considering only cardiac medical costs, this trend toward reduced medical costs was significant ($1240 vs $1442, P = .03). Conclusions At 24 weeks, patients with heart failure treated with omapatrilat had fewer hospitalizations and lower medical costs than patients treated with lisinopril. However, drug treatment costs were not available for this analysis. (Am Heart J 2002;143:1112-7.)     

Left atrial thrombus predicts transient ischemic attack in patients with atrial fibrillation

Background Atrial fibrillation (AF) is widely accepted as a direct cause of cardioembolic stroke from left atrial (LA) thrombus formation. However, the relationship between LA thrombus and transient ischemic attack (TIA) in patients with AF is less well established. Methods Two hundred sixty-one adult patients (mean age 66 ± 11 years, 220 men and 41 women) with AF undergoing transesophageal echocardiography (TEE) were prospectively followed up for TIA (mean duration 30.3 ± 20.6 months). Results LA thrombus was present in 18% (n = 46) and LA spontaneous echocardiographic contrast in 50% (n = 131) of the group. Nineteen of 261 patients had TIA during follow-up. Multivariate logistic regression showed congestive heart failure (CHF) as the only predictor of TIA when a model of clinical variables was constructed (odds ratio [OR] 2.7, P = .04). Age, sex, hypertension, and use of warfarin or aspirin were not predictors. When TEE variables were added to the model, LA thrombus became the only predictor of TIA (OR 7.7, P = .0001). Survival free of TIA (Kaplan-Meier) was significantly less (P = .0001) in patients with LA thrombus compared with those without, and the annual TIA event rate was 9.2% per year versus 1.9% per year (P <.0001), respectively. Conclusions To our knowledge, this is the first prospective study documenting an association between LA thrombus and TIA in patients with AF. Other TEE variables, including aortic atheromata, and clinical parameters were not independently predictive. These data support a likely thromboembolic mechanism for TIA from LA thrombus in patients with AF.     

Iodine-123 metaiodobenzylguanidine scintigraphic analysis of myocardial sympathetic innervation in patients with AL (primary) amyloidosis

Background Although a high incidence of myocardial adrenergic denervation has been reported in patients with familial amyloid polyneuropathy, assessment of cardiac sympathetic nerve function has not been available in patients with AL (primary) amyloidosis. Methods To test the hypothesis that myocardial sympathetic nerve innervation might be impaired and variable according to the presence or absence of clinical autonomic abnormalities and congestive heart failure in AL amyloidosis, we examined 25 patients by use of iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy. Results Ten of the 16 patients without autonomic symptoms and 5 of the 9 patients with autonomic neuropathy showed congestive heart failure. The heart/mediastinal activity (H/M) ratio (1.53 ± 0.06 vs 1.29 ± 0.05 at 3 hours, P < .001) and myocardial washout ratio (41.5% ± 4.8% vs 30.8% ± 4.0%, P < .001) of MIBG were significantly increased in patients without autonomic symptoms compared with patients showing autonomic neuropathy. In patient groups with and without autonomic dysfunction, patients demonstrating congestive heart failure exhibited a significantly decreased H/M ratio and increased washout compared with patients with no heart failure, and left ventricular fractional shortening was positively correlated with the H/M ratio and inversely correlated with the washout ratio. There were significant correlations between the low-frequency component of the heart rate variability and the H/M ratio and washout ratio in the entire patient population. Conclusions Patients with AL amyloidosis and no autonomic dysfunction showed variable degrees of enhanced cardiac adrenergic neuronal activity with presynaptic sympathetic dysfunction. In contrast, patients with AL amyloidosis and autonomic neuropathy exhibited prominent myocardial adrenergic denervation with normal or impaired sympathetic neural function of the heart. This study demonstrates that myocardial uptake and turnover of MIBG in patients with AL amyloidosis are heterogeneous and dependent on the presence or absence of congestive heart failure and cardiac autonomic dysfunction. (Am Heart J 2002;144:122-9.)     

Echocardiography-derived variables predict outcome in patients with nonischemic dilated cardiomyopathy with or without a restrictive filling pattern

Background Despite recent therapeutic advances, patients with heart failure caused by dilated cardiomyopathy (DCM) still have high morbidity and mortality rates. In this study, we sought to assess the prognostic value of echocardiographic variables in patients with DCM and to assess the impact of a restrictive left ventricle filling pattern. Design We conducted a retrospective cohort study of 337 patients with DCM, using the Royal Brompton Hospital Echocardiography database for the years 1994 to 1998. Methods and Results There were 337 patients with a mean age of 53 ± 15 years. One hundred ninety-five patients (58%) had a restrictive left ventricle filling pattern (RFP). There was a total of 74 deaths (22%) during the follow-up period (43 ± 25 months). RFP more than tripled the risk of death (adjusted hazard ratio 3.2, 95% CI 1.8-5.7, P = .003). RFP is correlated with isovolumic relaxation time, incoordinate wall-motion, amplitude of right ventricular long axis excursion on M-mode echocardiography, and mitral regurgitation. Conclusion RFP is a powerful independent predictor of mortality in patients with nonischemic DCM. The risk associated with RFP is greatest among patients who had short isovolumic relaxation time, mitral regurgitation, incoordinate wall-motion, and depressed amplitude of right ventricular long axis excursion. Thus, echocardiography-derived variables may stratify patients with heart failure with DCM who are at high risk, for whom aggressive medical treatment or heart transplantation should be considered early. (Am Heart J 2002;144:343-50.)     

Benefits of aspirin and beta-blockade after myocardial infarction in patients with chronic kidney disease

Background There have been no randomized trials of cardioprotective therapy after acute myocardial infarction in patients with chronic kidney disease who should be largely eligible for aspirin (acetylsalicylic acid; ASA) and beta-blockers (BB) as a base of therapy. Methods We analyzed a prospective coronary care unit registry of 1724 patients with ST-segment elevation myocardial infarction. Results Usage rates were 52.3%, 19.0%, 15.2%, and 13.5% for ASA and BB (ASA+BB), BB alone, ASA alone, and no ASA or BB therapy. Patients who received ASA+BB were more likely to be male, free of earlier cardiac disease, and recipients of thrombolysis. Conversely, the absence of ASA+BB was observed in patients with heart failure on admission, left bundle branch block, atrial and ventricular arrhythmias, and shock. The combination of ASA+BB was used in 63.9%, 55.8%, 48.2%, and 35.5% of patients with corrected creatinine clearance values of >81.5, 81.5 to 63.1, 63.1 to 46.2, and <46.2 mL/min/72 kg (P < .0001). ASA+BB was used in 40.4% of patients undergoing dialysis. The age-adjusted relative risk reduction for the inhospital mortality rate was similar among all renal groups and ranged from 64.3% to 80.0% (all P < .0001). Conclusion ASA+BB is an underused therapy in patients with acute myocardial infarction who have underlying kidney disease. (Am Heart J 2002;144:226-32.)     

Septal q waves as an indicator of risk of mortality in elderly patients with chronic heart failure

Background The absence of electrocardiographic septal q wave is a recognized marker of left ventricular disease. We aimed to investigate the prognostic significance of absent septal q waves in elderly (age >65 years) patients with chronic heart failure. Methods A total of 110 patients (mean age 73 ± 4 years) with New York Heart Association functional class II to IV and left ventricular ejection fraction of <45% were enrolled in the study. Standard 12-lead electrocardiograms were critically analyzed for the presence or absence of septal q waves in leads I, aVL, V₅, and V₆. Patient survival was determined from hospital and general practitioner records and National Statistics Registry at a mean follow-up of 4 years. Results Septal q waves were absent in 71 and present in 39 patients. The overall mortality rate was 47% (43 patients). The incidence of death was 49% (36 patients) in the group with no septal q waves and 18% (7 patients) in those who demonstrated septal q waves. On univariate analysis by Cox proportional hazard method, absence of septal q waves was found to be a strong marker of poor prognosis in CHF (P = .003, hazard ratio 1.40, 95% CI 1.10-1.67). Kaplan-Meier survival curves showed a significant difference in survival independent of age, New York Heart Association functional class, peak Vo₂, and QRS duration between these 2 groups. Conclusions Absence of the normal septal q wave on 12-lead electrocardiography, which may indicate structural heart disease and myocardial fibrosis, is an independent predictor of poor prognosis in elderly patients with CHF. (Am Heart J 2002;144:740-4.)     

Impact of cardiac catheterization-percutaneous coronary intervention timing on inhospital mortality

Background It is more convenient and less costly to perform percutaneous coronary interventions (PCIs) in the catheterization laboratory after catheterization, but there is some doubt as to whether it is harmful to patients. Other studies on this topic have been hampered by small sample sizes and an inability to separate patients who underwent PCI after catheterization in the same admission from patients who underwent PCI in a subsequent admission. Methods Data from New York's PCI registry were used to develop a statistical model that predicted inhospital mortality based on preprocedural patient characteristics and the timing of the PCI (at same time as catheterization [combined procedure] or in the same admission as catheterization, but not at the same time [staged procedure]). The difference in mortality for the timing options was compared after adjusting for patient risk factors. Results Patients undergoing combined catheterization and PCI were more likely to have undergone a previous PCI and less likely to have had chronic obstructive pulmonary disease, renal failure, a history of congestive heart failure, carotid disease, or diabetes than patients who underwent a staged procedure. After adjustment for patient risk, there were no significant differences in mortality for the 2 timing options (OR 1.14, P = .38 for combined vs staged procedures). However, patients who underwent combined procedures who had congestive heart failure in the same admission or who had Canadian Cardiovascular Society class IV had odds ratios significantly higher than congestive heart failure patients who underwent staged procedures (OR = 1.59, P = .04 and OR = 1.64, P = .04, respectively). Conclusions Combined procedures appear to have mortality as low as staged procedures on average, but are less effective for some groups of high-risk patients. (Am Heart J 2002;144:561-7.)