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Planar gated blood-pool imaging (GBPI) is a standard method for non-invasive assessment of left ventricular (LV) function. Gated blood-pool single photon emission computed tomographic (GBPS) data acquisition can be accomplished in the same time as GBPI, with the benefit of enabling visualization of all cardiac chambers simultaneously. The purpose of this investigation was to evaluate the degree to which automated and manual LVEF calculations agree with one another and with conventional GBPI LVEF measurements. GBPI studies were performed in 22 consecutive, unselected patients, followed by GBPS data acquisition. GBPS left ventricular ejection fraction (LVEF) calculations were performed by available software (NuSMUGA, Northwestern University, Chicago, IL) automatically and manually, using all LV gated short axis slices. Automatic LVEF assessed by GBPS correlated well with conventional planar GBPI (r = 0.88, P < 0.001). Mean planar GBPI LVEF was 50% +/- 12%, and mean GBPS automatic LVEF was significantly lower at 45% + 14% (P = 0.001), with a mean difference of 6% +/- 5%. Manual GBPS LVEF also correlated well with conventional planar GBPI (r = 0.90, P < 0.0001). Mean LVEF measurement by manual GBPS versus GBPI was significantly higher at 59% +/- 13%, with a mean difference of 10% +/- 6% (P < 0.001). Manual GBPS LVEF values were also significantly higher than automatically determined GBPS LVEF values (P < 0.001). It is concluded that LVEF values assessed by NuSMUGA GBPS software were reproducible, and automatic and manual values correlated well with conventional GBPI values. However, both automatic and manual GBPS calculations were significantly different from one another and from GBPI values, so that GBPI and NuSMUGA calculations cannot be considered to be equivalent.

Myocardial blood flow (MBF) reserve is impaired in patients with symptomatic chronic heart failure. Whether this is already present in asymptomatic left ventricular (LV) dysfunction, and whether it is affected by angiotensin converting enzyme (ACE) inhibition, is unknown. We examined MBF in 20 patients with asymptomatic LV dysfunction and compared them to healthy volunteers. MBF (reserve) was assessed with positron emission tomography (PET) and N-13 ammonia at rest, during dipyridamole stress test (DST) and during cold pressor test (CPT). Further, in the LV-dysfunction group, we studied the effects of 3 months treatment with ACE inhibition with a second PET study. Patients were randomized double-blind to perindopril 4 mg daily or placebo. MBF at rest was similar in controls and patients. DST-induced MBF reserve, however, was decreased in patients vs. controls (1.71+/-0.2 vs. 2.62+/-0.5, respectively p < 0.05). Also CPT-induced MBF was lower in patients (1.14+/-0.06 vs. 1.23+/-0.03, p < 0.05). After 3 months double-blind treatment, CPT-induced MBF decreased in the placebo group (from 1.12+/-0.02 to 0.93+/-0.06), but was preserved in the perindopril group (from 1.16+/-0.08 to 1.14+/-0.08 shifts from baseline: -0.19+/-0.05 vs. -0.02+/-0.07 respectively p = 0.07). This was compatible with a trend to a smaller increase in coronary vascular resistance during CPT (1.23+/-0.08 vs. 1.03+/-0.06, placebo vs. perindopril, p = 0.06). In patients with asymptomatic LV dysfunction, MBF, both after vasodilation and after CPT, is already impaired. ACE inhibition with perindopril during this short-term treatment had no significant effects.

Objectives: We sought to investigate the effect of angiotensin-converting enzyme (ACE) inhibition <9 h after myocardial infarction (MI) on left ventricular (LV) dilation in patients receiving thrombolysis., Background: The ACE inhibitors reduce mortality after MI. Attenuation of LV dilation has been suggested as an important mechanism., Methods: The data of 845 patients with three-month echocardiographic follow-up after MI were combined from three randomized, double-blind, placebo-controlled studies. The criteria for these studies included: 1) thrombolytic therapy; 2) ACE inhibition within 6 to 9 h; and 3) evaluation of LV dilation as the primary objective., Results: The ACE inhibitor was started 3.2+/-1.7 h after the patients' first (mainly, 85%) anterior MI. After three months, LV dilation was not significantly attenuated by very early treatment with an ACE inhibitor. The diastolic volume index was attenuated by 0.5 ml/m2 (95% confidence interval [CI] -1.5 to 2.5, p = 0.61), and the systolic volume index by 0.5 ml/m2 (95% CI -1.0 to 1.9, p = 0.50). Subgroup analysis demonstrated that LV dilation was significantly attenuated by ACE inhibitor treatment for patients in whom reperfusion failed. In contrast, LV dilation was almost unaffected by ACE inhibitor treatment in successfully reperfused patients., Conclusions: We could not demonstrate attenuation of LV dilation in patients receiving thrombolysis by ACE inhibitor treatment within 6 to 9 h after MI. We speculate that very early treatment with an ACE inhibitor has a beneficial effect on LV remodeling only in patients in whom reperfusion failed. Other mechanisms may be responsible for the beneficial effects of ACE inhibitors in successfully reperfused patients after MI.

Aims: In patients with coronary artery disease acetylcholine (a muscarinic agonist) causes vasoconstriction. The effect of atropine (a muscarinic antagonist) on coronary vasotone in patients with normal or impaired left ventricular function is unknown., Methods and Results: Twenty-four patients who required atropine infusion (to supplement heart rate response) during atrial pacing (pacing was conducted to assess ischaemia as part of an experimental protocol) were studied; 17 patients had normal and seven impaired left ventricular function (ejection fraction < or =0.40). Two control groups were selected from a large database (from patients in whom atrial pacing was carried out but to whom atropine was not administered) to match the normal (n=20) and dysfunction (n=10) groups. In the normal left ventricular function group atropine increased rate pressure product by 12 +/- 4%, as compared to those without atropine (P < 0.05). Left ventricular end diastolic pressure increased less in the atropine group (+40 +/- 8% vs +78 +/- 6%;P < 0.05). Arterial norepinephrine increased similarly in both groups, but coronary flow (as assessed by using a thermodiluting method in the coronary sinus) increased 23 +/ -4% more in the atropine group (P < 0.05). Further, there were lower levels of myocardial lactate production and ST-segment depression in the atropine group [lactate extraction +13 +/- 6% (atropine) vs -19 +/- 4% (controls), ST-segment depression 1. 3 +/- 0.6 (atropine) vs 1.8 +/- 0.2 mm (control), both P < 0.05 between groups]. In contrast, in the dysfunction group the overall effect of atropine was less pronounced., Conclusion: In patients with normal left ventricular function atropine improves coronary flow and reduces myocardial lactate production and ST-segment depression during atrial pacing, suggesting a reduction in myocardial ischaemia., (Copyright 1999 The European Society of Cardiology.)

In the present review, we discuss the role of clinical dosing of angiotensin converting enzyme (ACE) inhibitors in the treatment of left ventricular dysfunction. Although the precise mechanism of action of ACE inhibitors is still unresolved, the clinical efficacy of ACE inhibitors in the treatment of left ventricular dysfunction is well established. However, it is unclear whether the doses used in clinical trials translate directly into daily practice. Several reasons may cause differences between clinical practice and controlled trials: (1) clinical trials used higher doses than in normal practice; (2) some patients may be relatively 'resistant' to ACE inhibition; and/or (3) ACE activity increases during ACE inhibitor therapy and may provide escape mechanisms when the drug regimen is not strictly adhered to. Therefore, it is of interest that recent trials suggest that only the higher doses of ACE inhibition are clinically efficacious. In conclusion, it is suggested that optimal benefit from treatment with an ACE inhibitor in patients with left ventricular dysfunction requires sufficient and frequent dosing of the ACE inhibitor, e.g., enalapril 10 mg twice daily or captopril 25 mg three times daily.

Heart failure is a major and still growing medical and epidemiological problem, but in the last 10-20 years great progress has been made in its treatment. Alleviating symptoms is not (any longer) the only aim of the treatment; improving the life expectation or reducing the mortality has become a different, at least as important aim. Left ventricular dysfunction, even if asymptomatic, should be regarded, just as hypertension and hypercholesterolaemia, as a risk factor for which efficacious treatment is available and which consequently should be treated. A problem in this respect is that the effect of treatment of asymptomatic left ventricular dysfunction and of mild forms of heart failure is difficult to measure. Beta-blocking agents have proved to be the greatest gain in the treatment of heart failure in recent years, in addition to ACE inhibitors, diuretics and digoxin. These preparations should be prescribed with caution and due consideration. However, their favourable influence is such that use on a much larger scale than currently appears to be justified.

Aims: Most studies in chronic heart failure have only included patients with marked left ventricular systolic dysfunction (i.e. ejection fraction < or =0.35), and patients with mild left ventricular dysfunction are usually excluded. Further, exercise capacity strongly depends on age, but age-adjustment is usually not applied in these studies. Therefore, this study sought to establish whether (age-adjusted) peak VO2 was impaired in patients with mild left ventricular dysfunction., Methods: Peak VO2 and ventilatory anaerobic threshold were measured in 56 male patients with mild left ventricular dysfunction (ejection fraction 0.35-0.55; study population) and in 17 male patients with a normal left ventricular function (ejection fraction >0.55; control population). All patients had an old (>4 weeks) myocardial infarction. By using age-adjusted peak VO2 values, a 'decreased' exercise capacity was defined as < or = predicted peak VO2 - 1 x SD (0.81 of predicted peak VO2), and a severely decreased exercise capacity as < or = predicted peak VO2 - 2 x SD (0.62 of predicted peak VO2)., Results: Patients in the study population (age 52+/-9 years; ejection fraction 0.46+/-0.06) were mostly asymptomatic (NYHA class I: n=40, 76%), while 16 patients (24%) had mild symptoms, i.e. NYHA class II. All 17 controls (age 57+/-8 years) were asymptomatic. Mean peak VO2 was lower in patients with mild left ventricular dysfunction (23.6+/-5.7 vs 27.1+/-4.6 ml x min(-1) x kg(-1) in controls, P<0.05). In 75% of the study population patients (n=42) age-adjusted peak VO2 was decreased (NYHA I/II: n=29/13) and in 18% of them severely decreased (n=10; NYHA I/II: n=6/4). In contrast, only three patients (18%) in the control population had a decreased and none a severely decreased age-adjusted peak VO2., Conclusion: In patients with mild left ventricular dysfunction, who have either no or only mild symptoms of chronic heart failure, a substantial proportion has an impaired exercise capacity. By using age-adjustment, impairment of exercise capacity becomes more evident in younger patients. Patients with mild left ventricular dysfunction are probably under-diagnosed, and this finding has clinical and therapeutic implications.

Recently, different beta-blockers have been shown to be effective in the treatment of chronic heart failure (CHF), but the importance of their ancillary properties is not clear. Epanolol is a selective beta1-blocker with intrinsic sympathomimetic activity, which has been shown useful in angina pectoris, but its value in patients with left ventricular (LV) dysfunction and CHF is unknown. We examined the effects of epanolol in patients with LV dysfunction (n = 8; mean LV ejection fraction, 0.33 +/- 0.08) and compared them with patients with normal LV function (n = 8; mean LV ejection fraction, 0.52 +/- 0.04). Measurement of invasive hemodynamics and neurohormones was performed at rest and during myocardial ischemia, which was induced by atrial pacing. All measurements were performed before and after epanolol. Before epanolol, pacing-induced ischemia led to a similar increase in norepinephrine and coronary sinus blood flow in both groups. After epanolol, the increase in neurohormones was more pronounced in the group with LV dysfunction (norepinephrine, 1,130 +/- 164 pg/ml for patients with LV dysfunction vs. 637 +/- 41 pg/ml for normal subjects; p < 0.05). A similar effect was observed for angiotensin II. Further, in the LV-dysfunction group, coronary sinus blood flow increased less, and coronary vascular resistance decreased less (both values, p < 0.05). Despite the fact that the increase in double product was decreased to a similar extent in both groups, ischemia was reduced only in normal LV function (p < 0.05). In ischemic LV dysfunction, neurohumoral activation after epanolol may impair adequate coronary flow response, and this may limit its antiischemic properties. Because of the small size of the study, no definitive inference on the clinical benefit of epanolol in patients with ischemic LV function can be made from this study.

There is convincing evidence that (prolonged) episodes of myocardial ischemia lead to impairment of left ventricular (LV) function and ultimately to chronic congestive heart failure (CHF), but whether the opposite is also true has not been well established. We studied this issue in two groups of CHF patients with positron emission tomography (PET) by using [13N]ammonia (13NH3) as a tracer. In the first protocol we compared 12 patients with idiopathic dilated cardiomyopathy (who have normal coronary arteries) with 12 healthy controls. In the second protocol we studied a group of 24 patients with documented coronary artery disease (CAD). In this protocol, we compared patients with normal LV function to those with LV dysfunction and CHF. In patients with cardiomyopathy, myocardial blood flow at rest was normal but flow reserve (after dipyridamole infusion) was significantly impaired (1.7 +/- 0.08) compared with normal subjects (2.7 +/- 0.04; p <0.05). Furthermore, by examining [18F]fluorodeoxyglucose (18FDG) uptake, a perfusion-metabolism mismatch was observed in 24 +/- 6% of the myocardium in patients with cardiomyopathy as opposed to 0% of normals (p <0.05). In patients with CAD, myocardial blood flow reserve (measured in non-stenotic arteries to non-infarcted area) was impaired in CHF patients (1.7 +/- 0.06) compared to those with normal LV function (2.3 +/- 0.05; p <0.05). In both groups of CHF patients, the impairment of blood flow reserve showed a significant correlation with the severity of CHF. In conclusion, myocardial blood flow reserve is impaired in patients with CHF in proportion to the degree of CHF. Metabolic studies with 18FDG further show that, in patients with idiopathic dilated cardiomyopathy and CHF, flow-metabolism mismatch is present in a substantial part of the myocardium, suggesting a pathogenetic role for ischemia.

To study prognostic factors in patients with sustained ventricular tachycardias (VT) or ventricular fibrillation (VF) complicated by left ventricular dysfunction, we evaluated the predictive value of demographic, clinical, and hemodynamic parameters for cardiac mortality and sudden cardiac death in 85 patients with VT or VF and left ventricular ejection fraction < 0.45 (mean 0.27 +/- 0.10). Patients underwent serial drug testing and received appropriate antiarrhythmic treatment, with amiodarone given as last-resort therapy. During a follow-up of 24 +/- 13 months, 23 patients died of cardiac causes, and 18 of them died suddenly. Left ventricular ejection fraction < or = 0.27 and amiodarone treatment were related to greater cardiac mortality and increased risk of sudden cardiac death, whereas beta-blockade was associated with improved survival. In the multivariate model cardiac mortality was best predicted by a left ventricular ejection fraction < or = 0.27, and absence of beta-blockade and severe left ventricular dysfunction were the strongest predictors of sudden cardiac death. We conclude that severe left ventricular dysfunction predicts increased cardiac mortality and high risk of sudden cardiac death. Moreover, beta-blocking treatment is associated with lower cardiac mortality and a reduced risk of sudden cardiac death in patients with sustained VT or VF and depressed left ventricular function. beta-Blocking agents may therefore be an important addition to conventional antiarrhythmic treatment in patients with VT or VF and left ventricular dysfunction.

Objective: To review the importance of heart rate variability analysis in left ventricular dysfunction and heart failure and to assess the effects of drug treatment. In patients with left ventricular dysfunction or heart failure, a low heart rate variability is a strong predictor of a low probability of survival. Because drug treatment in these patients has rapidly changed over the past two decades, the effect of these drugs on heart rate variability needs special attention., Design: A study of published reports to give an overview of heart rate variability in patients with left ventricular dysfunction or heart failure and how it is affected by drug treatment., Results: Analysis of heart rate variability provides an easily obtained early marker for progression of disease. It seems to be more closely related to the degree of neurohumoral activation than to haemodynamic variables. Cardiovascular drugs may either stimulate or inhibit the degree of neurohumoral activation, and the effects of pharmacological intervention can be closely monitored with this method., Conclusions: The analysis of heart rate variability, including spectral analysis, is a novel non-invasive way to obtain potentially useful clinical information in patients with reduced left ventricular function. The effects of drug treatment on heart rate variability are in general consistent with their long-term effects in left ventricular dysfunction and heart failure.

To examine the predictive value of ventricular arrhythmias on ambulatory electrocardiographic (ECG) monitoring, 211 patients with left ventricular dysfunction and congestive heart failure (76% men, age 63 +/- 4 years, left ventricular ejection fraction 0.26 +/- 0.10) were studied. During a follow-up of 21 +/- 11 months, there were 45 cardiac deaths: 22 were due to progressive pump failure and 23 were sudden. Patients with a low left ventricular ejection fraction (< or = 0.27) and ventricular tachycardia on 24 h ECG were at higher risk of dying suddenly and from progressive pump failure (both P < 0.0001). Patients who died suddenly were found to have significantly longer (P = 0.003) and faster (P = 0.029) ventricular tachycardias on their baseline ambulatory ECG, than survivors. This association was not observed in patients who died of progressive pump failure. Therefore, low left ventricular ejection fraction and ventricular tachycardia on 24 h ECG recording predict an increased risk of cardiac mortality. Our results also suggest that longer and faster ventricular tachycardia recorded by 24 h ECG may identify patients at risk of sudden death, a finding which has not been described before.