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Renal insufficiency is common in patients with heart failure (HF), with both acute kidney injury and worsening renal function being associated with poor prognosis. The interplay between cardiac and renal failure has been termed the cardiorenal syndrome and is currently the subject of intense investigation. Urinary biochemistry has several advantages over blood or serum analyses, including lower costs, better patient comfort, and higher sensitivity to renal injury. However, urinalysis is currently not part of routine daily practice in cardiology. Recent advances in proteomics have allowed identification of numerous novel urinary biomarkers, many of which show promise in HF populations. In this review, we aim to provide an overview of both traditional and novel urinary biomarkers, examining evidence for diagnostic and prognostic value in HF as well as potential clinical utility.

Objectives The purpose of this study was to determine whether coenzyme Q10 is an independent predictor of prognosis in heart failure. Background Blood and tissue concentrations of the essential cofactor coenzyme Q10 are decreased by statins, and this could be harmful in patients with heart failure. Methods We measured serum coenzyme Q10 in 1,191 patients with ischemic systolic heart failure enrolled in CORONA (Controlled Rosuvastatin Multinational Study in Heart Failure) and related this to clinical outcomes. Results Patients with lower coenzyme Q10 concentrations were older and had more advanced heart failure. Mortality was significantly higher among patients in the lowest compared to the highest coenzyme Q10 tertile in a univariate analysis (hazard ratio: 1.50, 95% confidence interval: 1.04 to 2.6, p = 0.03) but not in a multivariable analysis. Coenzyme Q10 was not an independent predictor of any other clinical outcome. Rosuvastatin reduced coenzyme Q10 but there was no interaction between coenzyme Q10 and the effect of rosuvastatin. Conclusions Coenzyme Q10 is not an independent prognostic variable in heart failure. Rosuvastatin reduced coenzyme Q10, but even in patients with a low baseline coenzyme Q10, rosuvastatin treatment was not associated with a significantly worse outcome. (Controlled Rosuvastatin Multinational Study in Heart Failure [CORONA]; NCT00206310 )

Objectives We investigated whether plasma amino-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of cardiac dysfunction and prognosis measured in CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure), could be used to identify the severity of heart failure at which statins become ineffective. Background Statins reduce cardiovascular morbidity and mortality in many patients with ischemic heart disease but not, overall, those with heart failure. There must be a transition point at which treatment with a statin becomes futile. Methods In CORONA, patients with heart failure, reduced left ventricular ejection fraction, and ischemic heart disease were randomly assigned to 10 mg/day rosuvastatin or placebo. The primary composite outcome was cardiovascular death, nonfatal myocardial infarction, or stroke. Results Of 5,011 patients enrolled, NT-proBNP was measured in 3,664 (73%). The midtertile included values between 103 pmol/l (868 pg/ml) and 277 pmol/l (2,348 pg/ml). Log NT-proBNP was the strongest predictor (per log unit) of every outcome assessed but was strongest for death from worsening heart failure (hazard ratio [HR]: 1.99; 95% confidence interval [CI]: 1.71 to 2.30), was weaker for sudden death (HR: 1.69; 95% CI: 1.52 to 1.88), and was weakest for atherothrombotic events (HR: 1.24; 95% CI: 1.10 to 1.40). Patients in the lowest tertile of NT-proBNP had the best prognosis and, if assigned to rosuvastatin rather than placebo, had a greater reduction in the primary end point (HR: 0.65; 95% CI: 0.47 to 0.88) than patients in the other tertiles (heterogeneity test, p = 0.0192). This reflected fewer atherothrombotic events and sudden deaths with rosuvastatin. Conclusions Patients with heart failure due to ischemic heart disease who have NT-proBNP values

Aims Few prognostic models in heart failure have been developed in typically elderly patients treated with modern pharmacological therapy and even fewer included simple biochemical tests (such as creatinine), new biomarkers (such as natriuretic peptides), or, especially, both. In addition, most models have been developed for the single outcome of all-cause mortality. Methods and results We built a series of models for nine different fatal and non-fatal outcomes. For each outcome, a model was first built using demographic and clinical variables (Step 1), then with the addition of biochemical measures (serum creatinine, alanine aminotransferase, creatine kinase, thyrotrophin, apolipoproteins A-1 and B, and triglycerides) (Step 2) and finally with the incorporation of high-sensitivity C-reactive protein (hsCRP) and N-terminal pro B-type natriuretic peptide (NT-proBNP). Ranked according to the Wald χ2 value, age (56), ejection fraction (44), and body mass index (42) were most predictive of all-cause mortality in Step 1 (total model χ2 343). Creatinine was the most powerful predictor at Step 2 (48) and ApoA-1 ranked fifth (25), with the overall χ2 increasing to 440. Log NT-proBNP (167) was the most powerful of the 14 independently predictive variables identified at Step 3 and the overall χ2 increased to 600. NT-proBNP was the most powerful predictor of each other outcome. hsCRP was not a predictor of all-cause mortality but did predict the composite atherothrombotic outcome. Conclusion Of the two new biomarkers studied in prognostic models in heart failure, NT-proBNP, but not hsCRP, added substantial and independent predictive information, for a range of clinical outcomes, to that provided by simple demographic, clinical, and biochemical measures. ApoA-1 was more predictive than LDL or HDL.

Aims To describe the clinical course of patients with stable angina due to coronary heart disease without a history of cardiovascular (CV) events or revascutarization (isolated angina).Methods and results Of 7665 patients in a trial comparing long-acting nifedipine with placebo, 2170 (28%) had isolated angina. During a mean follow-up of 4.9 years, 147 of these died (1.4/100 patient-years), white 761 (8.7/100 patient-years) either died, or had a cardiac event or procedure. The first event was death in 82, myocardial infarction or heart failure in 112, coronary revascularization in 171, and chest pain requiring hospitalization in 396. Six hundred and twelve patients (6.8/100 patient-years) underwent coronary angiography (CAG), followed by revascularization in 371. Sixty-eight of 262 deaths or major cardiac events were preceded by chest pain requiring hospitalization or revascularization. Event-rates after CAG were higher than before. The stroke rate was 0.7/100 patient-years (75 patients).Conclusion Patients with stable isolated angina have tow rates of death and major cardiac events, but relatively high rates of chest pain requiring hospitalization despite contemporary management. Since the majority of deaths and major CV clinical events are not preceded by clear warning symptoms, the main clinical implication is that measures to prevent such events must target all patients.

Background and Objective: Published clinical trial data rarely allow assessment of the health care resource utilization implications of treatment. We give an example of how these can be assessed given appropriate tabulation of data. Methods: Data from a trial comparing long-acting nifedipine gastrointestinal therapeutic system to placebo in 7,665 patients with stable angina pectoris was analyzed. Results: Relative to placebo, nifedipine significantly increased mean cardiovascular (CV) event-free survival by 41 days but had no effect on mean survival. Per 100 years of follow-up, 78.1 patient-years of double-blind nifedipine administration reduced use of another calcium antagonist, an angiotensin converting enzyme inhibitor, an angiotensin receptor blocker, a diuretic and a cardiac glycoside by 1.54, 3.73, 2.63, 2.23, and 0.64 years, respectively, whereas 0.21 less hospitalization for overt heart failure, 0.47 less hospitalization for any stroke or transient ischemic attack, 0.8 less coronary angiogram, 0.38 less coronary bypass procedure, and 0.13 additional orthopedic procedure was required. Combining resource utilization with cost data for one particular hospital showed that one additional year of CV event-free survival costs an average additional EURO3,036 in the setting considered. Conclusion: Appropriately tabulated clinical trial data allows clinicians to judge the resource utilization implications and economic effect of treatment decisions. (c) 2007 Elsevier Inc. All rights reserved.

Background: Previous prospective outcome studies of statins have not provided any guidance on benefit-risk in patients with heart failure. Aim: The primary objective is to determine whether rosuvastatin (10 mg) reduces the combined endpoint of cardiovascular mortality, nonfatal myocardial infarction or non-fatal stroke (time to first event). The first secondary endpoint is all-cause mortality. Methods: CORONA is a randomized, double-blind, placebo-controlled trial. Briefly, men and women, aged 60 years with chronic symptomatic systolic heart failure of ischemic aetiology and ejection fraction 0.40 (NYHA class III and IV) or 0.35 (NYHA class II) were eligible if they were not using or in need of cholesterol lowering drugs. Results: Mean age was 73 years (n=5016; 24% women), with 37% in NYHA II and 62% in NYHA III, ejection fraction 0.31, total cholesterol 5.2 mmol/L. Sixty percent have a history of myocardial infarction, 63% hypertension, and 30% diabetes. Patients are well treated for heart failure with 90% on loop or thiazide diuretics, 42% aldosterone antagonists, 91% ACE inhibitor or AT-I blocker, 75% beta-blockers, and 32% digitalis. Conclusion: CORONA is important for three main reasons: (1) A positive result is very important because of the high risk of the population studied, the increasing prevalence of elderly patients with chronic symptomatic systolic heart failure in our society, and the health economic issues involved. (2) If negative, new mechanistic questions about heart failure have to be raised. (3) If neutral we can avoid unnecessary polypharmacy.

Aims The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula estimates glomerular filtration rate (GFR) better than the simplified Modification of Diet in Renal Disease (sMDRD) formula in numerous populations. It has not previously been validated in heart failure patients.Methods and results The GFR was measured in 120 patients with chronic systolic heart failure (CHF) using [I-125]iothalamate clearance (GFR(IOTH)) and estimated using the sMDRD and CKD-EPI equations. Accuracy, bias, and prognostic performance were compared. Cockcroft-Gault, CKD-EPI serum cystatin C, and CKD-EPI creatinine-serum cystatin C equations were compared in secondary analyses. Mean age was 59 +/- 12 years, 80% were male. Mean LVEF was 29 +/- 10%. Mean GFR(IOTH) was 74 +/- 27 mL/min/1.73 m(2), and mean estimated GFR was 66 +/- 23 mL/min/1.73 m(2) (CKD-EPI) and 63 +/- 21 mL/min/1.73m(2) (sMDRD). CKD-EPI showed less bias than sMDRD (-8 +/- 15 vs. -11 +/- 16 mL/min/1.73 m(2), P Conclusion The CKD-EPI equation more accurately estimates measured GFR than the sMDRD equation in CHF patients, with less bias and greater accuracy and precision. The prognostic power of all GFR assessments was equivalent. Based on better performance and equal risk prediction, we believe the CKI-EPI equation should be the preferred creatinine-based GFR estimation method in heart failure patients, particularly those with preserved or moderately impaired renal function.

OBJECTIVES We sought to study the effect of angiotensin-converting enzyme inhibition on exercise-induced myocardial ischemia. BACKGROUND Although angiotensin-converting enzyme inhibitors have been shown to reduce ischemic events after myocardial infarction, few data are available regarding their direct anti-ischemic effects in patients with coronary artery disease. METHODS We studied 43 patients (average age 63 +/- 8 years) with exercise-induced myocardial ischemia (greater than or equal to0.1 mV ST depression, despite optimal beta blockade) and normal left ventricular function (ejection fraction >0.50). In a double-blind, placebo-controlled parallel design, patients were treated with angiotensin-converting enzyme inhibitor (enalapril 10 mg twice daily) or placebo. Assessments were made aii-er three weeks (short-term) and 12 weeks (long-term). RESULTS At baseline, the groups were well matched for all clinical characteristics. After three weeks, there was a slight but not significant increase in time to 0.1 mV ST depression in both groups (p = NS); rate pressure product (RPP = heart rate x systolic blood pressure) was also unaffected. After 12 weeks, however, time to 0.1 mV ST depression further increased in the enalapril group (5.6 +/- 1.9 min) but was unchanged in the placebo group (4.4 +/- 1.3 min; p

BACKGROUND: Metoprolol can improve haemodynamics in chronic heart failure, but survival benefit has not been proven. We investigated whether metoprolol controlled release/extended release (CR/XL) once daily, in addition to standard therapy, would lower mortality in patients with decreased ejection fraction and symptoms of heart failure. METHODS: We enrolled 3991 patients with chronic heart failure in New York Heart Association (NYHA) functional class II-IV and with ejection fraction of 0.40 or less, stabilised with optimum standard therapy, in a double-blind randomised controlled study. Randomisation was preceded by a 2-week single-blind placebo run-in period. 1990 patients were randomly assigned metoprolol CR/XL 12.5 mg (NYHA III-IV) or 25.0 mg once daily (NYHA II) and 2001 were assigned placebo. The target dose was 200 mg once daily and doses were up-titrated over 8 weeks. Our primary endpoint was all-cause mortality, analysed by intention to treat. FINDINGS: The study was stopped early on the recommendation of the independent safety committee. Mean follow-up time was 1 year. All-cause mortality was lower in the metoprolol CR/XL group than in the placebo group (145 [7.2%, per patient-year of follow-up]) vs 217 deaths [11.0%], relative risk 0.66 [95% CI 0.53-0.81]; p=0.00009 or adjusted for interim analyses p=0.0062). There were fewer sudden deaths in the metoprolol CR/XL group than in the placebo group (79 vs 132, 0.59 [0.45-0.78]; p=0.0002) and deaths from worsening heart failure (30 vs 58, 0.51 [0.33-0.79]; p=0.0023). INTERPRETATION: Metoprolol CR/XL once daily in addition to optimum standard therapy improved survival. The drug was well tolerated.

Anginal patients who remain symptomatic despite optimally dosed beta blockade may also be given dihydropyridine calcium antagonists. This treatment regimen was examined in a double-blind parallel, randomized, controlled study in 147 patients with angina and positive bicycle exercise tests despite optimal beta blockade with atenolol (heart rate at rest

The gastrointestinal therapeutic system formulation of nifedipine enables a once-daily dosing resulting in predictable, relatively constant plasma concentrations. To evaluate the efficacy and safety of this formulation and to compare this with the β-blocker atenolol, we conducted a double-blind, randomised, multi-centre study in 129 male patients with documented exercise induced angina pectoris. After 4 weeks' treatment, nifedipine (60 mg), improved time to onset of 0.1 mV ST-segment depression from 536 s by 72 ± 117 s, time to onset of pain from 619 s by 56 ± 120 s, and total exercise time from 685 s by 40 ± 88 s. Atenolol 100 mg, had a comparable effect, time to onset of 0.1 mV ST-segment depression improved from 496 s by 53 ± 129 s, time to onset of pain from 572 s by 57 ± 118 s, and total exercise time from 653 s by 33 ± 99 s. Between group analysis revealed no statistically significant differences for these exercise parameters. Atenolol, but not nifedipine, significantly reduced heart rate and systolic blood pressure at rest and during exercise ( P P = 0.01) more vasodilation related side effects with nifedipine. These data demonstrate that gastrointestinal therapeutic system formulation of nifedipine and atenolol as once-daily monotherapy are equally effective and safe, but with different effects on exercise parameters.

Objectives.This study assessed the effects of digoxin and ibopamine on variables of heart rate variability in relation to neurohormonal activation.Background.Analysis of heart rate variability can be used to study the autonomic dysfunction that characterizes chronic heart failure. In the Dutch Ibopamine Multicenter Trial, patients with heart failure were found to have increased neurohormonal activation with placebo therapy but not with digoxin and ibopamine therapy.Methods.We studied 59 patients with mild to moderate heart failure (mean [±SEM]age 60 ± 1 years, mean ejection fraction 0.30 ± 0.01). Patients were randomized to double-blind treatment with digoxin (0.25 mg [n = 22]), ibopamine (100 mg three times a day [n = 19]) or placebo (n = 18); background therapy consisted of furosemide (up to 80 mg).Results.After 3 months, plasma norepinephrine levels had increased with placebo, whereas they decreased with digoxin (+31 vs. −60 pg/ml, respectively, p < 0.01). With ibopamine, a nonsig nificant decrease was observed (−27 pg/ml, p = 0.10). All variables of heart rate variability showed a deterioration in the placebo group. With digoxin, the percent differences between successive RR intervals >50 ms (pNN50) increased (+ 1.7 ± 0.9%, p < 0.01), along with absolute and normalized high frequency power (+40 ± 33 ms2, p < 0.05 and +2.4 ± 1.7%, p < 0.01, respectively). These changes were observed during daytime hours only and were most pronounced in patients with the most impaired baseline heart rate variability. With ibopamine, nonsignificant trends similar to the changes with digoxin were observed.Conclusions.In patients with early stages of heart failure, digoxin may prevent a progressive deterioration in heart rate variability, whereas ibopamine does not show statistically significant effects. The changes in heart rate variability with digoxin parallel an observed decrease in neurohormonal activation. Digoxin apparently enhances cardiac vagal tone in the setting of neuroendocrine activation.

There is increasing evidence that clinical deterioration in manifest chronic heart failure is related to both hemodynamic and neurohumoral factors. Only few data are available, however, on the progression of disease in its early stages, when treatment has not yet been initiated. The aim of this study was therefore to examine the changes in clinical and neurohumoral variables that occur over 6 months in patients with clinically stable and untreated heart failure, and to evaluate the influence of drugs that may affect these variables. Accordingly, we studied 64 patients with heart failure who were in New York Heart Association functional class II (88%) and III (12%). They were randomized to double-blind treatment with the oral dopamine agonist ibopamine (100 mg 3 times daily; n = 22), digoxin (0.25 mg once daily; n = 22) or placebo (n = 20). Their age (mean +/- SD) was 60 +/- 8 years, and left ventricular ejection fraction (mean +/- SD) was 0.33 +/- 0.08. Of the 64 patients, 56 (88%) completed the 6-month study period (p = NS between groups). Exercise time decreased in patients treated with placebo after 6 months (median -62 seconds; p < 0.05 vs baseline), but it increased with ibopamine (+48 seconds), and digoxin (+17 seconds; both p < 0.05 vs placebo). Plasma norepinephrine increased in the placebo group after 6 months (median + 31 pg/ml, p < 0.05 vs baseline), but decreased in patients receiving active drug treatment (ibopamine: -24 pg/ml, digoxin: -98 pg/ml, both p < 0.05 vs placebo). Plasma renin and aldosterone levels were unchanged after 6 months in the placebo group, but digoxin therapy slightly reduced plasma renin concentration (-5 microU/ml; p < 0.05 vs placebo).(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary artery disease is an increasingly common medical problem in the elderly, and relatively few studies investigating drug therapy focus on this population. To assess the efficacy and safety of the calcium channel blocker, felodipine, and isosorbide mononitrate (ISMN), as adjunct to optimal beta-blocker therapy in elderly patients, a placebo-controlled, double-blind study was conducted in 46 patients, aged between 65 and 80 years, with documented stress-induced angina pectoris and myocardial ischemia. With use of a latin-square design, with 3 periods of 4 weeks each, exercise testing was performed after each period. Felodipine, 5 mg once daily, significantly improved both time to ischemic threshold and pain threshold (p = 0.02 and p = 0.003, respectively, vs placebo), and tended to increase total exercise time (p = 0.06 vs placebo). In contrast, ISMN, 20 mg twice daily, did not significantly affect these parameters. Comparison of the 2 active treatment arms showed that, overall, felodipine was more effective than ISMN, with a statistically significant difference for time to ischemic threshold (p = 0.02). With regard to safety, felodipine was also better tolerated than ISMN, which led to more patients discontinuing study medication with ISMN (p0.05 between ISMN and felodipine). It is concluded that in elderly patients who are treated with optimal beta blockade, felodipine, but not ISMN, leads to an additional significant reduction in ischemic parameters during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

International audience; We assessed the independent effects of beta blockers, calcium antagonists, lipid-lowering drugs, angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), anti-platelet drugs, vitamin K antagonists, percutaneous coronary intervention (PCI) and coronary artery by-pass grafting (CABG) on mortality and on the composite endpoint of death, myocardial infarction, stroke or heart failure in patients with stable angina pectoris. We estimated the effects of the interventions used at baseline by multivariate Cox regression and during follow-up by G-estimation in 7,665 patients followed for a mean of 5 years in the ACTION trial. Adjusted hazard ratios (95% confidence intervals) comparing all cause mortality among users during follow-up to non-users were 1.01 (0.91, 1.09) for beta blockade, 0.82 (0.75, 0.89) for ACEIs or ARBs, 0.93 (0.87, 0.98) for calcium antagonists, 0.54 (0.49, 0.62) for lipid-lowering drugs, 0.49 (0.42, 0.53) for anti-platelet drugs, 0.74 (0.69, 0.78) for PCI, and 0.91 (0.82, 0.98) for CABG. Effects on the composite endpoint were less marked. This observational study confirms that ACEIs or ARBs, lipid-lowering and anti-platelet drugs as used in the everyday management of stable angina have independent secondary preventive effects. Calcium antagonists, PCI and CABG also appear to improve outcome.

To examine the relationship between baseline intermittent claudication and outcomes in patients enrolled in the Controlled Rosuvastatin Multinational Trial in Heart Failure trial (CORONA). Intermittent claudication is an independent predictor of worse outcome in coronary heart disease, but its prognostic importance in heart failure (HF) is unknown. Patients aged ≥60 years with NYHA class II-IV, low ejection fraction HF of ischaemic aetiology were enrolled in CORONA. Rosuvastatin did not reduce the primary outcome or all-cause mortality. Methods and results: To determine whether intermittent claudication was an independent predictor of clinical outcomes, a three-step multivariable model was built: (i) demographic/clinical variables, (ii) biochemical measures added, (iii) high-sensitivity C-reactive protein and N-terminal pro B-type natriuretic-peptide added. Of the 5011 patients, 637 (12.7) had intermittent claudication at baseline. Patients with intermittent claudication were more likely to be male (83 vs. 75), be a current smoker (19 vs. 9), and have diabetes mellitus (36 vs. 29) relative to those without intermittent claudication. Over a median 33-month follow-up, 2168 patients died or were hospitalized for HF. Patients with intermittent claudication had an increased risk of death (any cause) (adjusted hazard ratio 1.36, 95 CI 1.19-1.56, P < 0.0001), death from worsening HF (1.35, 1.03-1.77, P = 0.028), sudden death (1.24, 1.00-1.54, P = 0.05), and risk of non-fatal or fatal myocardial infarction (time to first event 1.67, 1.24-2.27, P < 0.001). In the full multivariable model, intermittent claudication remained an independent predictor of most outcomes evaluated. Conclusion: Intermittent claudication is a relatively common symptom in ischaemic HF and an independent predictor of worse outcome.Clinical Trial Registration Information: NCT00206310-http://clinicaltrials.gov/ct2/show/ NCT00206310?term=corona&rank=2. © 2010 The Author.

BACKGROUND: Patients with systolic heart failure have generally been excluded from statin trials. Acute coronary events are uncommon in this population, and statins have theoretical risks in these patients. METHODS: A total of 5011 patients at least 60 years of age with New York Heart Association class II, III, or IV ischemic, systolic heart failure were randomly assigned to receive 10 mg of rosuvastatin or placebo per day. The primary composite outcome was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Secondary outcomes included death from any cause, any coronary event, death from cardiovascular causes, and the number of hospitalizations. RESULTS: As compared with the placebo group, patients in the rosuvastatin group had decreased levels of low-density lipoprotein cholesterol (difference between groups, 45.0%; P

Since the 1960s, calcium antagonists have been available for the treatment of angina pectoris and hypertension. The first of this class, nifedipine, was introduced and readily accepted as the third treatment option for angina, alongside beta-blockers and nitrates. However, the short-acting formulations of nifedipine had pharmacokinetic properties that were far from ideal and in 1995, several studies involving various dosing regimens reported possible dangerous effects in secondary prevention. Since then, large-scale, randomized controlled trials with new controlled-released formulations of nifedipine have demonstrated the effectiveness and safety of this drug. As a consequence of these results, guidelines for both hypertension and angina pectoris have been recently reconsidered, and have put the modern formulations of calcium channel blockers in a pole position. Within this group of therapeutics, nifedipine gastrointestinal therapeutic system has a unique position and it cannot be replaced by other controlled-release formulations of nifedipine, the pharmaceutical properties of which have yet to be tested in large-scale outcome trials.

Contains fulltext : 48732.pdf (Publisher’s version ) (Open Access) BACKGROUND: Current guidelines recommend an early invasive strategy for patients who have acute coronary syndromes without ST-segment elevation and with an elevated cardiac troponin T level. However, randomized trials have not shown an overall reduction in mortality, and the reduction in the rate of myocardial infarction in previous trials has varied depending on the definition of myocardial infarction. METHODS: We randomly assigned 1200 patients with acute coronary syndrome without ST-segment elevation who had chest pain, an elevated cardiac troponin T level (> or =0.03 mug per liter), and either electrocardiographic evidence of ischemia at admission or a documented history of coronary disease to an early invasive strategy or to a more conservative (selectively invasive) strategy. Patients received aspirin daily, enoxaparin for 48 hours, and abciximab at the time of percutaneous coronary intervention. The use of clopidogrel and intensive lipid-lowering therapy was recommended. The primary end point was a composite of death, nonfatal myocardial infarction, or rehospitalization for anginal symptoms within one year after randomization. RESULTS: The estimated cumulative rate of the primary end point was 22.7 percent in the group assigned to early invasive management and 21.2 percent in the group assigned to selectively invasive management (relative risk, 1.07; 95 percent confidence interval, 0.87 to 1.33; P=0.33). The mortality rate was the same in the two groups (2.5 percent). Myocardial infarction was significantly more frequent in the group assigned to early invasive management (15.0 percent vs. 10.0 percent, P=0.005), but rehospitalization was less frequent in that group (7.4 percent vs. 10.9 percent, P=0.04). CONCLUSIONS: We could not demonstrate that, given optimized medical therapy, an early invasive strategy was superior to a selectively invasive strategy in patients with acute coronary syndromes without ST-segment elevation and with an elevated cardiac troponin T level.

Background The effects of β-blockade with different extent of angiotensin-converting enzyme inhibitors (ACEI) and digitalization are unknown. To assess the effect of metoprolol succinate controlled release/extended release (CR/XL) combined with high versus low doses of ACEI and digitalis, we analyzed data from The Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF) in which patients with heart failure and left ventricular ejection fraction ≤40% were randomized to metoprolol CR/XL versus placebo. Methods and results Outcome was analyzed separately for those on a low dose (≤median) of the ACEI or digitalis versus high dose (>median). The mean dose of ACEI in the high-dose group (n = 1457) was 3 times higher than that in the low-dose group (n = 2094). Mortality was reduced to a similar extent in the high- and low-dose ACEI subgroups (RR = .69 versus .64, respectively). Corresponding figures for combined mortality/all hospitalization and for mortality/hospitalization for heart failure were .85 versus .83, and .70 versus .68, respectively. Likewise, reduction in total mortality with metoprolol CR/XL was similar in patients receiving no digitalis (n = 1447; RR = .56), low dose (n = 1122; RR = .71), or high dose (n = 1421; RR = .71). Conclusion This analysis of MERIT-HF demonstrates consistent and similar improvement in outcome of patients receiving metoprolol CR/XL when combined with either a high or low dose of an ACEI or digitalis, or no digitalis at all. Thus regardless of ACEI and digitalis dose and whether patients are treated with digitalis or not, it is very important to add a β-blocker to the existing heart failure therapy. β-blockers should not be withheld until target doses of ACEI have been achieved.

We evaluated the prognostic value of renal function in an initially “untreated” population with mild heart failure and compared the prognosis of this population with a matched controlled population. During a follow-up of 13 years (mean 11.7), 90 patients (56%) died. Mortality was higher compared with a matched controlled population. Multivariate Cox regression analysis demonstrated that beside the well-established risk markers of left ventricular ejection fraction and heart rate, renal function (estimated glomerular filtration rate, hazard ratio 1.16/10 ml/min/1.73 m2, p = 0.003) was the only additional independent predictor of cardiovascular mortality in patients with early heart failure. The aims of the present study were to evaluate whether renal function is an independent risk marker for cardiovascular mortality in patients with mild heart failure, and to establish the long-term prognosis of this population. Patients included in this analysis participated in the Dutch Ibopamine Multicenter Trial (DIMT), a multicenter heart failure study, as previously described.1 In summary, the study was a double-blind 6-month comparison of ibopamine, digoxin, and placebo in patients with mild heart failure (HF). Patients ranged in age from 18 to 75 years and were clinically stable for ≥2 weeks. Chronic heart failure was characterized by clinical signs and symptoms, and a radionuclide left ventricular (LV) ejection fraction

Background— Brain natriuretic peptide (BNP) and norepinephrine (NE) are strongly related to severity of and are independent predictors of outcome in heart failure. The long-term effects of angiotensin receptor blockers on BNP and NE in heart failure patients are not known. Methods and Results— Both BNP and NE were measured in 4284 patients randomized to valsartan or placebo in the Valsartan Heart Failure Trial (Val-HeFT) at baseline and 4, 12, and 24 months after randomization. The effects of valsartan were tested by ANCOVA, controlling for baseline values and concomitant ACE inhibitors and/or β-blockers. BNP and NE concentrations were similar at baseline in the 2 groups and were decreased by valsartan starting at 4 months and up to 24 months. BNP increased over time in the placebo group. At the end point, least-squares mean (±SEM) BNP increased from baseline by 23±5 pg/mL in the placebo group (n=1979) but decreased by 21±5 pg/mL (n=1940) in the valsartan group ( P P =0.0003). Concomitant therapy with both ACE inhibitors and β-blockers significantly reduced the effect of valsartan on BNP but not on NE ( P for interaction=0.0223 and 0.2289, respectively). Conclusions— In Val-HeFT, the largest neurohormone study in patients with symptomatic chronic heart failure, BNP and NE rose over time in the placebo group. Valsartan caused sustained reduction in BNP and attenuated the increase in NE over the course of the study. These neurohormone effects of valsartan are consistent with the clinical benefits reported in Val-HeFT.

Dofetilide may be advantageous in terminating atrial fibrillation/atrial flutter (AFl) when there are contraindications for class I drugs (left ventricular dysfunction and/or manifest myocardial ischemia) and beta blockers. In particular, its successful outcome in usually drug-resistant AFl is promising and underscores the importance of selective class III action for terminating AFl.

Background Chronic heart failure (CHF) has high morbidity and mortality rates despite treatment with angiotensin-converting enzyme inhibitors, diuretics, and digoxin. Adjunctive vasodilation through calcium channel blockade has been suggested as potentially useful. However, the first-generation calcium channel blockers, including the dihydropyridine nifedipine, showed disappointing results in CHF. The second-generation dihydropyridines were expected to be of more value, and of all the calcium channel blockers, these drugs were the ones most studied in patients with CHF. Methods and Results The Medline databank was used to search studies in human beings (published in 1990 or later) that used dihydropyridines in patients with CHF. The references of the studies found were subsequently checked for additional data. In 17 studies and more than 2000 patients with CHF, no consistent beneficial effect was observed with regard to exercise tolerance and functional capacity, whereas plasma neurohormones were not affected. On the other hand, in general, no worsening of CHF was seen with these second-generation dihydropyridines. Two larger studies (PRAISE and V-HeFT III) have given some estimates on the long-term effects of dihydropyridines, and no overall influence on mortality rate was found. Of note, subanalysis of the PRAISE study has suggested that in patients with a nonischemic cause of CHF, amlodipine might have a beneficial effect on survival. Conclusions In this review we have focused on the efficacy and safety of dihydropyridines in patients with CHF, as reported in recent trials. The data do not support the use of dihydropyridines when primarily given as treatment for CHF. The results, however, suggest that these drugs can be safely given to patients with left ventricular dysfunction or CHF who need additional treatment for angina pectoris or hypertension.

The effect of exercise training on quality of life and exercise capacity was studied in 67 patients with mild to moderate chronic heart failure (CHF; age: 65.6+/-8.3 years; left ventricular ejection fraction: 26.5+/-9.6%). Patients were randomly allocated to either a training group or to a control group. After intervention a significantly larger decrease in Feelings of Being Disabled (a subscale of the Heart Patients Psychological Questionnaire) and a significantly larger increase in the Self-Assessment of General Well-Being (SAGWB) were observed in the training group. Exercise time and anaerobic threshold were increased in the training group only. The increase in exercise time was related to both Feelings of Being Disabled and SAGWB. We conclude that supervised exercise training improves both quality of life and exercise capacity and can be safely performed by chronic heart failure patients.

Objectives. We sought to assess the prognostic value of heart rate variability measures, including Poincare plots, in patients with mild to moderate chronic heart failure. Background. Mortality is high in patients with heart failure, and many of them die suddenly. However, identification of high risk patients, particularly those,vith an increased risk for sudden death, has remained difficult. Methods. We studied 95 patients with heart failure (mean [+/-SD] age 60 +/- 8 years, left ventricular ejection fraction 0.29 +/- 0.09, Nea York Heart Association functional class II [81%] and III [19%]) during up to 4 years of follow-up. Heart rate variability measures and Poincare plots were obtained from 24-h Holter recordings. Results. During follow up, 17 (18%) of the 95 patients died. In 15 patients, death was cardiac related (11 patients experienced sudden death). None of the conventional time and frequency domain measures of heart rate variability were related to survival. In contrast, abnormal Poincare plots identified a significantly higher risk for all-cause cardiac death (Cox proportional hazards ratio 5.7, 95% confidence interval [CI] 1.6 to 20.6, univariate analysis);Ind for sudden cardiac death (hazards ratio 6.8, 95% CI 1.5 to 31.4) compared with those with normal Poincare plots. Patients with abnormal Poincare plots were shown to have a lower left ventricular ejection fraction (0.26 +/- 0.10 vs. 0.31 +/- 0.08, p

Angiotensin-converting enzyme (ACE) inhibition is currently the cornerstone of congestive heart failure (CHF) therapy, but these drugs are not tolerated in up to 20% of patients. For these patients, therapeutic alternatives with comparable efficacy are needed. Felodipine, a vasoselective dihydropyridine calcium antagonist with a slow onset of action and a long plasma half-life, may be such an agent. Therefore, the efficacy and safety of felodipine were examined and compared with enalapril using a double-blind design. We studied 46 patients with a left ventricular ejection fraction0.40, peak oxygen consumption20 ml.min-1.kg-1, and symptoms of CHF despite therapy with diuretics and digoxin. After 16 weeks of therapy, there were no statistically significant differences in peak oxygen consumption (felodipine +1.6, enalapril +2.5 ml.min-1.kg-1) and exercise tolerance (felodipine +61 seconds, enalapril +64 seconds). Quality-of-life parameters were affected slightly better by felodipine than by enalapril. Plasma norepinephrine decreased by 143 pg.ml-1 with enalapril and by 12 pg.ml-1 with felodipine (p0.20 between groups). Both drugs were generally well tolerated. These data suggest that felodipine and enalapril have comparable effects on exercise parameters in patients with CHF. Neurohumoral activation was not observed with either drug.

that regional LV dysfunction is not responsible for this nonspecificity. Our results differ from those of Breithardt et al,4 who detected late potentials in only 9% of patients with normal wall motion compared with 46% of patients with regional akinesia or dyskinesia. However, the recording methodology and semiqualitative criteria for diagnosing late potentials in their study differed markedly from those currently used by most investigators2,3 and used in our report’. In addition, the results differ primarily in the higher frequency of late potentials recorded in our control group, which also exceeds the frequency of an abnormal SAECG in normal subjects reported previously in several other studies.2,5,6 However, our “normal” patients had undergone cardiac catheterization and were much older than the normal subjects in those studies, which consisted of nurses and medical residents2 or other healthy volunteers who had not undergone cardiac catheterization.5,6 Increasing age has been found recently to independently increase the incidence of late potentials,7 and probably accounts for the frequency of late potentials in our control group. This finding of a reduced positive predictive value of the SAECG in older patients has important implic;ations for the prospective value of this test, because the question of susceptibility to VT is far more likely to be raised in older patients with suspected heart disease than it is in young, healthy people.

BACKGROUND: Heart failure (HF) disease management programs are widely implemented, but data about their effect on outcome have been inconsistent. METHODS: The Coordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure (COACH) was a multicenter, randomized, controlled trial in which 1023 patients were enrolled after hospitalization because of HF. Patients were assigned to 1 of 3 groups: a control group (follow-up by a cardiologist) and 2 intervention groups with additional basic or intensive support by a nurse specializing in management of patients with HF. Patients were studied for 18 months. Primary end points were time to death or rehospitalization because of HF and the number of days lost to death or hospitalization. RESULTS: Mean patient age was 71 years; 38% were women; and 50% of patients had mild HF and 50% had moderate to severe HF. During the study, 411 patients (40%) were readmitted because of HF or died from any cause: 42% in the control group, and 41% and 38% in the basic and intensive support groups, respectively (hazard ratio, 0.96 and 0.93, respectively; P = .73 and P = .52, respectively). The number of days lost to death or hospitalization was 39 960 in the control group, 33 731 days for the basic intervention group (P = .81), and 34 268 for the intensive support group (P = .49). All-cause mortality occurred in 29% of patients in the control group, and there was a trend toward lower mortality in the intervention groups combined (hazard ratio, 0.85; 95% confidence interval, 0.66-1.08; P = .18). There were slightly more hospitalizations in the 2 intervention groups (basic intervention group, P = .89; and intensive support group, P = .60). CONCLUSIONS: Neither moderate nor intensive disease management by a nurse specializing in management of patients with HF reduced the combined end points of death and hospitalization because of HF compared with standard follow-up. There was a nonsignificant, potentially relevant reduction in mortality, accompanied by a slight increase in the number of short hospitalizations in both intervention groups. Clinical Trial Registry http://trialregister.nl Identifier: NCT 98675639.

Intravenous streptokinase administration is now a widely applied therapy for patients in the early hours of acute myocardial infarction (AMI). The dosages used do not appear to be based on comparative clinical investigations. Therefore a double-blind randomized trial was carried out to establish the optimal dose of streptokinase. A total of 189 patients who had symptoms of AMI for less than 4 hours were treated with 200,000, 750,000, 1,500,000 or 3,000,000 IU streptokinase intravenously. At coronary angiography 2.8 +/- 2.7 hours (mean +/- standard deviation) after the start of streptokinase infusion, patency of the infarct-related coronary artery was observed in 38, 75, 60 and 82% of the patients, respectively, in the 4 groups. The result of the dosage of 200,000 IU was significantly poorer than that of the other dosages (p less than 0.01). The result of a dosage of 3,000,000 IU was significantly better than that of 1,500,000 IU (p less than 0.05), but the differences with 750,000 IU were not significant. Blood transfusion was required in 4 patients (2%), distributed over the 4 groups in 0, 2, 1 and 1 of the patients. One patient had major bleeding; this patient had been treated with 750,000 IU. The 3-month mortality-rate in the whole study population was 5%. Thus, of the 4 doses of streptokinase tested, 750,000 IU is the minimal therapeutic dosage, and the arguments for 1,500,000 IU as standard therapy for comparison with other fibrinolytic drugs are poor. The best results in this study were achieved with 3,000,000 IU, but further research will be needed to establish the efficacy and safety of this new regimen.

Felodipine (FEL) is a vasoselective dihydropyridine calcium antagonist that has shown promising results in smaller congestive heart failure (CHF) studies. Angiotensin converting enzyme inhibitors (ACEI) are the cornerstone of CHF therapy, but many patients can not be treated with these drugs because of side effects or contraindications. We compared the effects of FEL. 10 mg b.Ld., and enalapril (ENA), 10 mg b.Ld., in a double blind, parallel study in 50 patients with CHF. At baseline and after 16 weeks treatment cardiopulmonary exercise test, neurohormone sampling, Holter recording and quality of life questionaires were assessed. Patients Fifty patients with CHF, NYHA class II–III, mean age 64 ± 7 yr., mean LVEF of 26 ± 9%, mean peak oxygen consumption of 14.8 ± 3.5 ml/min/kg. mean norepinephrine 683 ± 470 pg/ml and mean plasma renin activity of 0.9 ± 0.8 ng/ml/hr were randomized, after a 2 week placebo period, to FEL and ENA. Results Exercise duration was increased 63 sec and peak oxygen consumption 0.7 ml/kg/min after FEL, and 60 sec and 1.4 ml/kg/min after ENA (P = NS). Rate pressure product (RPP) at peak exercise was significantly lowered by Fel (p l 0.005). Plasma norepinephrine decreased after both Fel and ENA by 46 and 150 pg/ml respectively, whereas plasma renin increased by 0.7 and 4.1 ng/ml/hr respectively (both P = NS). FEL patients significantly better results on quality of life score. Holter recordings revealed no proarhytmias with either drug. Side effects were minor with both drugs. Discussion The vasoselective calcium antagonist FEL demonstrated equal efficacy in exercise parameters, and was somewhat superior in quality of life parameters, if compared to ENA. The massive vasodilation induced by FEL, as demonstrated by the RPP was not accompanied by an activation of the neurohormonal system, so often observed with other vasodilating agents. Conclusion FEL can be seriously considered as an alternative treatment for ACEI in CHF patients. A direct comparison between FEL and ACEI in CHF, with special emphasis on long term efficacy and mortality seems of interest.

Background Physical training currently constitutes an important part of treatment of heart failure patients. So far, no data are available on the effects of regular exercise in elderly (aged > 65 years) heart failure patients. Methods In a prospective trial, patients with chronic heart failure (New York Heart Association class II and III) were randomly assigned to a training group and a control group. Patients in the training group performed additional exercises three times a week, while patients in the control group continued regular treatment. To analyse the influence of age, both groups were subdivided into subjects younger than and older than 65 years. The effect of training on exercise parameters was evaluated by means of a treadmill test. Quality of life aspects were evaluated with the help of the Heart Patients Psychological Questionnaire and a single-question Self Awareness of General Well-Being test. Results Comparison of changes between groups revealed that training increased the duration of the exercise test and improved aspects of quality of life in the trained patients aged both younger than and older than 65 years. Conclusion Exercise training is equally effective in patients aged younger than and older than 65 years.

This symposium opened with the presentation of information that will be of assistance in the development of future diagnostic strategies and therapy in angina pectoris. As the principal symptom of ischemic heart disease (IHD), angina requires accurate and prompt diagnosis to enable effective treatment. For example, one common assumption is that a patient may be typically perceived of as a middle-aged man with effort angina, often associated with other illnesses. However, data presented by Dr. Pepine, from a study in 5125 U.S. outpatients, suggests that patients are most likely to be women and the elderly, with high levels of associated illnesses. Despite the availability of a number of surgical and medical therapies, IHD remains a serious health problem. The issue of the relative costs of surgical and medical therapies has been studied by Dr. Cleland through a cost–bene~t and cost-effectiveness analysis model in a hypothetical cohort of 100 patients. The degree of symptom control was a signi~cant determinant in choice of therapy. In patients with well-controlled symptoms, medical therapy offers the most costeffective option. In particular, calcium antagonists, beta-blockers, and long-acting nitrates have formed the mainstay of antiischemic management of IHD. A rational approach to the treatment of chronic myocardial ischemia requires an understanding of the pathophysiology of coronary artery disease and the treatment options available. These two issues are discussed in detail by Dr. Cohn, including the use of combination therapy and new agents under investigation. One of the aims of improving current therapy should be to reduce unwanted interactions, for example, by careful combination of particular classes of drug. Traditional calcium antagonists, in particular, have been associated with a number of side effects, such as headache and _ushing, caused by abrupt vasodilation. The new generation of dihydropyridine calcium antagonists may offer an effective alternative to the original calcium antagonists or beta-blocking drugs because of their improved pharmacodynamic and pharmacokinetic pro~le. This ef~cacy is demonstrated by the multicenter, double-blind study of Dr. van Kesteren, which compared amlodipine with controlled-release diltiazem in 132 patients. The results show bene~ts to both groups of patients, with reduced numbers of withdrawals and adverse events seen in the amlodipine group. Overall, the ef~cacy, tolerability, and once-daily dosing may favor the use of third-generation calcium channel blockers, such as amlodipine, in the treatment of coronary artery disease. Twenty-four hour coverage can improve patient compliance and, more importantly, can provide anti-ischemic control during those periods of the day when there are high rates of ischemic attack. The Circadian Anti-ischemia Program in Europe (CAPE) trial recently showed that, compared with placebo, amlodipine added to background therapy signi~cantly reduced both symptomatic and asymptomatic ischemia over 24 hours in patients with chronic stable angina. The aims of the ongoing CAPE II trial are to compare the effects of amlodipine with diltiazem in treating ischemia, to investigate the ability of these two drugs to manage the circadian pattern of myocardial ischemia, and to evaluate combined therapy of amlodipine plus a betablocker and diltiazem plus a nitrate. The results from this study will demonstrate the optimal medical approach to ischemia suppression in patients with coronary artery disease and add further support to the use of calcium antagonists in future therapeutic recommendations.

Acute hemodynamic and hormonal responses to ramipril in comparison with captopril were studied in 10 patients with moderate to severe congestive heart failure in an open, randomized study. Both drugs were given to 5 patients each in 2 increasing doses on 2 successive days. After 5 mg of ramipril angiotensin converting enzyme (ACE) activity was significantly decreased during 24 hours with a maximum decrease 4 hours after administration. Mean arterial blood pressure decreased from 84 ± 5 to 62 ± 5 mm Hg at 4 hours and 71 ± 4 mm Hg at 12 hours, respectively, after this dose. Capillary wedge pressure decreased from 19 ± 1 mm Hg to 13 ± 1 mm Hg at 4 hours with a maximum increase in cardiac output from 3.8 ± 0.3 liters/min to 4.4 ± 0.3 liters/min at 2 hours. No significant cardiac effects were present 8 hours after administration. After 10 mg of ramipril, cardiac and hormonal effects showed a quicker onset of action and longer duration compared with the 5 mg dose. Mean arterial pressure decreased to 61 ± 6 mm Hg. Similar effects were seen after captopril, but with a significantly shorter duration. Mean arterial pressure decreased from 82 ± 4 mm Hg to 64 ± 5 mm Hg after 12.5 mg and to 58 ± 6 mm Hg after 25 mg of captopril. In patients with congestive heart failure ramipril has the hemodynamic profile of a long-acting and potent ACE inhibitor. Significant cardiac effects are present during 4 to 8 hours and ACE activity is still significantly inhibited 24 hours after a single dose of ramipril. Severe hypotension may occur in the acute phase; therefore, the starting dose should be ≤2.5 mg and further therapy should be individualized.

The relation of central haemodynamic changes to subsequent mortality and peak enzyme activity was investigated in 190 patients with acute myocardial infarction. The mean delay time from onset of symptoms to the haemodynamic study was 7.2 hours. Major exclusion criteria were heart rate less than 65 beats min-1, systolic blood pressure less than 105 mmHg and lung rales to a distance of greater than 10 cm above the lung bases. Nine patients (4.7%) died within 15 days and 16 patients (8.4%) within 90 days after the infarction. Compared to survivors, non-survivors were characterized by baseline depression of cardiac index, stroke volume index and left ventricular stroke work index, while pulmonary capillary wedge pressure and peripheral resistance were increased. However, a wide overlap between survivors and non-survivors makes the predictive value low in the individual patient. Peak serum aspartate aminotransferase (S-ASAT) activity was weakly related to baseline pulmonary capillary wedge pressure (r = 0.28; P less than 0.001) and stroke volume index (r = -0.22; P less than 0.01). The correlation to pulmonary capillary wedge pressure was only found in anterior (r = 0.34) infarcts. Peak serum lactate dehydrogenase (LD1) was not correlated with baseline haemodynamics.

To evaluate the necessity of an objective cardiopulmonary exercise test in the selection procedure of patients for heart failure studies, 50 patients with congestive heart failure New York Heart Association (NYHA) class II and III and a left ventricular ejection fraction less than 40% were subjected to a cardiopulmonary exercise test. The results of the exercise test were compared with the independent clinical estimation of NYHA class and data of measurements obtained at rest. The NYHA classification separated the patients with a mild to moderate impairment of aerobic capacity from patients with a moderate to severe impairment of aerobic capacity very well, but 32% of the NYHA class II patients had a near normal aerobic capacity, and 29% of the NYHA class III patients had a very severe impairment of aerobic capacity, more compatible with NYHA class IV. Only data from exercise measurements showed differences between groups. The determination of maximal aerobic capacity for an objective assessment of patients' performance at exercise is necessary for a proper selection procedure of patients for heart failure studies.

In an attempt to investigate the changes in left ventricular haemodynamics following uncomplicated myocardial infarction 95 patients with definite electrocardiographic signs of infarction, without clinical signs of cardiac failure, were monitored with a Swan Ganz catheter for the first 24 hours after admission to hospital. The median delay from onset of symptoms was 6.8 hours. Mean heart rate increased (83-86 beats/min; P less than 0.05) while stroke volume index fell (38.4-36.6 ml/m2; P less than 0.05); cardiac index therefore remained unchanged during the observation period. As a result of a fall in arterial pressure both systemic vascular resistance and left ventricular stroke work index fell significantly (P less than 0.01). Pulmonary wedge pressure also fell (13.6-10.5 mm Hg; P less than 0.001), but this fall was confined to patients whose initial reading was above the median of 13 mm Hg. Pulmonary wedge pressure fell both among the 41 patients who required some medical therapy (15.6-10.8 mm Hg; P less than 0.001) and the 54 who received no medication throughout the 24 hours (12.0-9.8 mm Hg; P less than 0.05). The 39 patients with anterior wall infarction had higher baseline pulmonary wedge pressure and systemic vascular resistance than the 42 with inferior wall infarction. Later the stroke volume and stroke work index were persistently lower reflecting the greater degree of impairment of left ventricular function in anterior wall infarction. In conclusion, following an uncomplicated myocardial infarction, cardiac index was maintained, despite a fall in stroke volume, by an increase in heart rate. Pulmonary wedge pressure showed both a spontaneous fall and a fall in those patients given additional medical therapy during the study period.

The central hemodynamic effects of metoprolol in acute myocardial infarction have been studied in a multicenter, double-blind, randomized trial. One hundred and ninety patients with acute myocardial infarction not previously on β blockers with heart rate >65 beats/min and blood pressure >105 mm Hg and without clinical signs of serious heart failure were included. After insertion of a pulmonary artery catheter, patients were randomized to metoprolol, 15 mg intravenously, and 50 mg 4 times a day orally (n = 95) or placebo (n = 95) with a mean delay of 7.2 hours. Hemodynamic measurements were made at baseline and repeatedly during 24 hours. Heart rate, systolic blood pressure and cardiac index were all immediately reduced by 10 to 20% in the metoprolol group and the difference compared with placebo was maintained throughout the 24 hours (p

OBJECTIVES This retrospective study sought to assess differences in graft patency and clinical outcome between women and men after coronary artery bypass graft surgery (CABG). BACKGROUND A less favorable clinical outcome has been reported in women as compared with men. Its relation to graft patency has not been studied. METHODS We analyzed one-year follow-up data of 912 patients (120 women) who entered a randomized clinical drug trial. All patients received vein grafts; in 494 patients (56 women) internal mammary artery (IMA) grafts were also used. Graft patency was assessed by coronary angiography at one year. Primary clinical end points were myocardial infarction, revascularization procedures and death; secondary clinical end points included recurrent angina, heart failure and arrhythmias. RESULTS Occlusion rates of vein grafts were 16.7% in women and 12.4% in men (odds ratio [OR] 1.62, 95% confidence interval [CI] 0.88 to 3.00, p = 0.12); occlusion rates of IMA grafts were 3.4% and 5.7% in women and men, respectively (OR 0.56, 95% CI 0.08 to 3.96, p = 0.56). Primary clinical end points were observed in 16.7% of women and 9.2% of men (OR 1.97, 95% CI 1.10 to 3.34, p = 0.022), and any clinical end point in 41.7% of women and 25.8% of men (OR 2.06, 95% CI 1.39 to 3.04, p = 0.0004). Myocardial infarction (15% vs. 7.6%, OR 2.15, 95% CI 1.24 to 3.75, p = 0.013) and recurrent angina (26.7% vs. 15.4%, OR 2.00, 95% CI 1.28 to 3.11, p = 0.004) occurred most frequently. Multivariate regression analysis did not identify gender as an independent risk factor for graft occlusion or the clinical end points. Graft occlusion was an independent predictor of the composite primary clinical end point (OR 2.75, 95% CI 1.59 to 4.75, p = 0.0003) and each of the secondary clinical end points. The observed differences were due to an imbalance of risk factors at baseline and to surgical and graft characteristics. CONCLUSIONS One-year occlusion rates of vein and IMA grafts were comparable in women and men. Clinical outcome was related to graft patency and was less favorable in women owing to their uneven distribution of risk factors among both groups.