Evidence of partially preserved endothelial dilator function in diseased coronary arteries

OBJECTIVE—To examine the effects of substance P (endothelium dependent vasodilator) and glyceryl trinitrate (endothelium independent vasodilator) on epicardial coronary arteries in patients with normal coronary angiograms and patients with coronary artery disease.
DESIGN—Intracoronary infusions of normal saline, the receptor mediated nitric oxide stimulant substance P (5.6 and 27.8 pmol/min each for five minutes), and glyceryl trinitrate (250 µg bolus) were given in 24 patients with coronary artery disease and stable angina, and in nine patients with normal angiograms. The diameter of proximal and distal coronary segments was measured by computerised quantitative angiography
RESULTS—Proximal segments of patients with coronary artery disease dilated less than those of patients with normal angiograms in response to 27.8 pmol/min substance P (mean (SEM): 7.9 (1.3)% v 15 (2.3)% respectively, p < 0.01). The proximal segments of diseased arteries also dilated less than those of "normal" arteries in response to glyceryl trinitrate (10.2 (1.6)% v 18.4 (2.9)%, respectively, p < 0.01). The responses of distal segments to substance P and glyceryl trinitrate were similar in the two patient groups. There were correlations (all p < 0.001) between the coronary diameter after substance P and after glyceryl trinitrate in normal proximal segments (r = 0.94) and normal distal segments (r = 0.64), in diseased proximal segments (r = 0.95) and diseased distal segments (r = 0.89), and for coronary stenoses (r = 0.93).
CONCLUSIONS—Proximal segments of patients with coronary disease dilated less than the proximal segments of "normal" patients in response to substance P and glyceryl trinitrate. The response to substance P is substantial and closely correlated with the response to glyceryl trinitrate in both "normal" patients and those with coronary disease. This suggests that although the proximal segments of diseased coronary arteries have a reduced capacity to dilate in response to direct stimulation of smooth muscle cell relaxation, they retain much of their endothelium dependent vasodilator function.


Keywords: endothelium; nitric oxide; coronary artery disease; glyceryl trinitrate     

Regulation of peripheral vascular tone in patients with heart failure: contribution of angiotensin II

Objective—To determine directly the contribution of angiotensin II to basal and sympathetically stimulated peripheral arteriolar tone in patients with heart failure.
Design—Parallel group comparison.
Subjects—Nine patients with New York Heart Association grade II-IV chronic heart failure, and age and sex matched controls.
Interventions—Forearm plethysmography, lower body negative pressure, local intra-arterial administration of losartan, angiotensin II, and noradrenaline, and estimation of plasma hormone concentrations.
Main outcome measures—Forearm blood flow responses, plasma hormone concentrations.
Results—Baseline blood pressure, heart rate, and forearm blood flow did not differ between patients and controls. In comparison with the non-infused forearm, losartan did not affect basal forearm blood flow (95% confidence interval −5.5% to +7.3%) or sympathetically stimulated vasoconstriction in controls. However, the mean (SEM) blood flow in patients increased by 13(5)% and 26(7)% in response to 30 and 90 µg/min of losartan respectively (p < 0.001). Lower body negative pressure caused a reduction in forearm blood flow of 20(5)% in controls (p = 0.008) and 13(5)% (p = 0.08) in patients (p = 0.007, controls v patients). Blood flow at 90 µg/min of losartan correlated with plasma angiotensin II concentration (r = 0.77; p = 0.03). Responses to angiotensin II and noradrenaline did not differ between patients and controls.
Conclusions—Losartan causes acute local peripheral arteriolar vasodilatation in patients with heart failure but not in healthy control subjects. Endogenous angiotensin II directly contributes to basal peripheral arteriolar tone in patients with heart failure but does not augment sympathetically stimulated peripheral vascular tone.

Keywords: angiotensin II;  heart failure;  peripheral vascular tone;  sympathetic nervous system     

Pravastatin and endothelium dependent vasomotion after coronary angioplasty: the PREFACE trial

OBJECTIVE—To test the hypothesis that the 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitor pravastatin ameliorates endothelium mediated responses of dilated coronary segments: the PREFACE (pravastatin related effects following angioplasty on coronary endothelium) trial.
DESIGN—A double blind, randomised, placebo controlled, multicentre study.
SETTING—Four hospitals in the Netherlands.
PATIENTS—63 non-smoking, non-hypercholesterolaemic patients scheduled for elective balloon angioplasty (pravastatin 34, placebo 29).
INTERVENTIONS—The effects of three months of pravastatin treatment (40 mg daily) on endothelium dependent vasomotor function were studied. Balloon angioplasty was undertaken one month after randomisation, and coronary vasomotor function tests using acetylcholine were performed two months after balloon angioplasty. The angiograms were analysed quantitatively.
MAIN OUTCOME MEASURES—The efficacy measure was the acetylcholine induced change in mean arterial diameter, determined in the dilated segment and in an angiographically normal segment of an adjacent non-manipulated coronary artery.
RESULTS—Increasing acetylcholine doses produced vasoconstriction in the dilated segments (p = 0.004) but not in the normal segments. Pravastatin did not affect the vascular response to acetylcholine in either the dilated segments (p = 0.09) or the non-dilated sites. Endothelium dependent vasomotion in normal segments was correlated with that in dilated segments (r = 0.47, p < 0.001). There were fewer procedure related events in the pravastatin group than in the placebo group (p < 0.05).
CONCLUSIONS—Endothelium dependent vasomotion in normal segments is correlated with that in dilated segments. A significant beneficial effect of pravastatin on endothelial function could not be shown, but in the dilated segments there was a trend towards a beneficial treatment effect in the pravastatin group.


Keywords: angioplasty; endothelium; acetylcholine; pravastatin     

β Blockade in congestive heart failure: persistent adverse haemodynamic effects during chronic treatment with subsequent doses

Objective—To determine whether the acute adverse haemodynamic effects of β blockade in patients with congestive heart failure persist during chronic treatment.
Design—Sequential haemodynamic evaluation of heart failure patients at baseline and after three months of continuous treatment with the β₁ selective antagonist metoprolol.
Setting—Cardiac care unit in university hospital.
Patients—26 patients with moderate to severe congestive heart failure (New York Heart Association grade II to IV) and background treatment with digoxin, diuretics, and angiotensin converting enzyme inhibitors, and with a left ventricular ejection fraction < 25%.
Methods—Baseline variables included a six minute walk, maximum oxygen consumption, and right heart catheterisation. All patients received metoprolol 6.25 mg orally twice daily initially and the dose was gradually increased to a target of 50 mg twice daily. Haemodynamic measurements were repeated after three months of treatment, both before (trough) and after drug readministration.
Results—Long term metoprolol had functional, exercise, and haemodynamic benefits. It produced decreases in heart rate, pulmonary capillary wedge pressure, and systemic vascular resistance, and increases in cardiac index, stroke volume index, and stroke work index. However, when full dose metoprolol was readministered during chronic treatment, there was a reduction in cardiac index (from 2.8 (SD 0.46) to 2.3 (0.38) l/min/m², p << 0.001) and stroke work index (from 31.4 (11.1) to 26.6 (10.0) g.m/m², p < 0.001) and an increase in systemic vascular resistance (from 943 (192) to 1160 (219) dyn.s.cm⁻⁵, p << 0.001).
Conclusions—Adverse haemodynamic effects of β blockers in heart failure persist during chronic treatment, as shown by worsening haemodynamic indices with subsequent doses.

Keywords: heart failure;  β blockers;  adverse effects     

Treatment with epoprostenol reverts nitric oxide non-responsiveness in patients with primary pulmonary hypertension

OBJECTIVE—To assess whether long term treatment with epoprostenol might restore primary non-responsiveness to nitric oxide (NO) in patients with primary pulmonary hypertension.
METHODS—Seven patients with primary pulmonary hypertension receiving intravenous epoprostenol continuously because of failure of NO to influence pulmonary haemodynamics during initial testing were followed over a period of 13-29 months. Afterwards, acute vascular reactivity towards NO was tested again during right heart catheterisation.
RESULTS—Administration of NO after continuous epoprostenol treatment for a mean period of 18 months improved arterial oxygen saturation (p < 0.01) and cardiac index (p < 0.05), and decreased mean pulmonary artery pressure (p < 0.01) and total pulmonary vascular resistance (p < 0.01) in patients previously unresponsive to NO.
CONCLUSIONS—Long term treatment with epoprostenol reverts initial refractoriness to NO in patients with primary pulmonary hypertension. Thus the addition of NO to epoprostenol treatment might cause further improvement in the course of the disease.


Keywords: primary pulmonary hypertension; epoprostenol; vascular reactivity     

Bradykinin induced dilatation of human epicardial and resistance coronary arteries in vivo: effect of inhibition of nitric oxide synthesis

Objective—To clarify whether endothelium derived nitric oxide contributes to exogenous bradykinin induced dilatation of human epicardial and resistance coronary arteries in vivo.
Design—Quantitative coronary angiography and Doppler flow velocity measurements were used to determine the effects of the nitric oxide synthesis inhibitor, N^G-monomethyl-L-arginine (L-NMMA), on bradykinin induced dilatation of the epicardial and resistance coronary arteries.
Setting—Hiroshima University Hospital.
Patients—20 patients (16 men and four women, mean (SD) age 56 (9) years) with angiographically normal smooth epicardial coronary arteries.
Interventions—Serial infusions of bradykinin (0.5, 1.5, and 2.5 µg/min) were given into the left coronary ostium before and after L-NMMA infusion (60 µmol/min).
Main outcome measures—Epicardial coronary diameter, coronary blood flow, and coronary vascular resistance.
Results—Bradykinin-induced epicardial coronary vasodilatation after L-NMMA (dilatation by 2.5 µg/min, 3.8(1.4)% in the proximal and 5.9(1.8)% in the distal segments, mean (SEM)) was less (p < 0.001, respectively) than before L-NMMA (11.7(2.5)% and 15.1(2.0)%, respectively). In contrast, L-NMMA did not affect the bradykinin induced increase in coronary blood flow and decrease in coronary vascular resistance.
Conclusions—Endothelium derived nitric oxide contributes to bradykinin induced dilatation of epicardial coronary arteries, but may be less important in coronary resistance vasodilatation.

Keywords: bradykinin;  nitric oxide;  coronary artery;  coronary blood flow     

Microvascular involvement in systemic sclerosis: laser Doppler evaluation of reactivity to acetylcholine and sodium nitroprusside by iontophoresis

OBJECTIVES—To investigate the skin vasodilatory response to iontophoretically applied acetylcholine (Ach), an endothelium dependent vasodilator, and to sodium nitroprusside (SNP), an endothelium independent vasodilator, in patients with systemic sclerosis (SSc).
METHODS—Eleven SSc patients were preliminarily studied (10 females, mean age 40.5; mean disease duration 6.5 years), and 16 age and sex matched control subjects. By means of laser Doppler flowmetry skin blood flow was evaluated at third finger, at baseline, and after post-ischaemic hyperaemia test and during iontophoretically transcutaneous application of 1% solution of Ach and SNP.
RESULTS—No significant differences in basal skin blood flow were detected between SSc patients and controls. Cutaneous vasodilatory response to ischaemia, Ach, and SNP was significantly less pronounced in SSc patients compared with controls (p<0.001). Moreover, among SSc patients a lower (p< 0.05) vasodilatory response to Ach compared with ischaemia and SNP was recorded.
CONCLUSIONS—These data confirm a reduction of skin digital vasodilatory reserve in SSc patients and suggest a defect of both endothelial dependent arteriolar relaxation and wall compliance in the pathogenesis of this dysfunction.

Keywords: systemic sclerosis; iontophoresis; endothelium; acetylcholine; sodium nitroprusside; post-ischaemic hyperaemia     

Effects of coronary revascularisation on myocardial blood flow and coronary vasodilator reserve in hibernating myocardium

OBJECTIVE—Previous studies have suggested that resting myocardial blood flow is within normal limits in most chronically dysfunctional left ventricular segments which improve function after coronary artery revascularisation (hibernating myocardium). The aim of this study was to assess myocardial blood flow and coronary vasodilator reserve in hibernating myocardium before and after coronary revascularisation.
PATIENTS AND METHODS— 30 patients with multivessel coronary disease undergoing coronary revascularisation (21 patients with bypass grafting and nine with coronary angioplasty), and 21 age and sex matched healthy volunteers (controls). Myocardial blood flow (MBF, ml/min/g) was measured by positron emission tomography using oxygen-15 water at rest and after dipyridamole (MBFdip, 0.56 mg/kg in four minutes). Coronary vasodilator reserve was calculated as MBFdip/MBF. Regional wall motion was assessed with echocardiography.
RESULTS—Before revascularisation there were 48 remote and 275 dysfunctional myocardial segments, of which 163 (59%) improved function after revascularisation (hibernating). In hibernating segments coronary vasodilator reserve before revascularisation was significantly lower than in remote segments (1.97 (0.7), p < 0.0001) and controls (3.2 (1.5), p < 0.0001). In hibernating segments, myocardial blood flow remained unchanged after revascularisation (0.94 (0.3) v 0.95 (0.3) ml/min/g, p = 0.3) while coronary vasodilator reserve increased (1.47 (0.7) v 1.98 (1.0), p < 0.0001). Myocardial blood flow was similar in remote, hibernating segments before and after revascularisation and in controls.
CONCLUSIONS—This study confirms that myocardial blood flow at rest in hibernating myocardium is within normal limits in most segments, and that hibernating myocardium is characterised by an impaired coronary vasodilator reserve which improves significantly after coronary revascularisation.


Keywords: hibernating myocardium; myocardial blood flow; heart failure; positron emission tomography     

Atrial fibrillation is associated with a lower exercise capacity in male chronic heart failure patients

Objective—To study the influence of atrial fibrillation on peak oxygen uptake (peak O₂) in chronic heart failure. An unfavourable effect of atrial fibrillation has been shown in several patient populations, but the results have not been consistent in chronic heart failure.
Methods—Data were analysed from male heart transplant candidates who were able to perform graded bicycle ergometry until exhaustion with respiratory gas analysis and measurement of heart rate. Patients in atrial fibrillation (n = 18) were compared with patients in sinus rhythm (n = 93).
Results—Age, weight, height, and aetiology of chronic heart failure did not differ significantly between the two groups. Cardiac catheterisation at supine rest showed that heart rate was comparable, but that stroke volume and cardiac output were lower (p < 0.05) in atrial fibrillation. Systolic and diastolic left ventricular function, assessed by radionuclide angiography at rest, were not significantly different. Peak O₂ (mean (SD): 13.8 (3.6) v 17.1 (5.6) ml/kg/min; p < 0.01) and peak work load (78 (27) v 98 (36) W; p < 0.05) were lower in the patients with atrial fibrillation, though respiratory gas exchange ratio and Borg score were similar in the two groups. Patients with atrial fibrillation had a higher heart rate sitting at rest before exercise (93 (16) v 84 (16) beats/min) and at peak effort (156 (23) v 140 (25) beats/min) (p < 0.05).
Conclusions—Atrial fibrillation is associated with a 20% lower peak O₂ in patients with chronic heart failure, suggesting that preserved atrial contraction or a regular rhythm, or both, are critical to maintain cardiac output and exercise performance.

Keywords: peak oxygen uptake;  exercise capacity;  chronic heart failure;  atrial fibrillation     

Cognitive impairment in heart failure with Cheyne-Stokes respiration

OBJECTIVES—To document the degree of cognitive impairment in stable heart failure, and to determine its relation to the presence of Cheyne-Stokes respiration during sleep.
SUBJECTS—104 heart failure patients and 21 healthy normal volunteers.
METHODS—Overnight oximetry was used (previously validated as a screening tool for Cheyne-Stokes respiration in heart failure). Cognitive function was assessed using a battery of neuropsychological tests. Left ventricular function was assessed by echocardiography.
RESULTS—Heart failure patients performed worse than the healthy volunteers in tests that measured vigilance. Reaction times were 48% slower (0.89 (0.03) s v 0.60 (0.05) s; p < 0.005) and they hit twice as many obstacles on the Steer Clear simulator (75 (6.4) v 33 (4.6); p < 0.005). Cognitive impairment within the heart failure group was unrelated to either the presence of Cheyne-Stokes respiration, the degree of left ventricular dysfunction, or indices of nocturnal oxygenation.
CONCLUSIONS—Vigilance was impaired in heart failure but this did not appear to be related to the presence of Cheyne-Stokes respiration during sleep. Impaired vigilance as measured on the Steer Clear test has been associated with an increased risk of motor vehicle accidents. The issue of fitness to drive in heart failure requires further attention.


Keywords: Cheyne-Stokes respiration; cognitive function; heart failure; driving     

Midodrine: a role in the management of neurocardiogenic syncope

Objective—To determine the benefit of midodrine, an α agonist, on symptom frequency and haemodynamic responses during head up tilt in patients with neurocardiogenic syncope.
Setting—Cardiovascular investigation unit (a secondary and tertiary referral centre for the investigation and management of syncope).
Patients—16 outpatients (mean (SD) age 56 (18) years; five men) with frequent hypotensive symptoms (more than two syncopal episodes and fewer than 20 symptom free days per month), and reproducible syncope with glyceryl trinitrate (GTN) during head up tilt.
Design and intervention—Randomised double blind placebo controlled study. Patients were randomised to receive either placebo or midodrine for one month. Symptom events were recorded during each study month. At the end of each study month patients completed a quality of life scoring scale (Short Form 36) and a global assessment of therapeutic response. They received GTN with head up tilt for measurement of heart rate (electrocardiography), phasic blood pressure (digital photoplethysmography), and thoracic fluid index (transthoracic impedance plethysmography) during symptom provocation.
Results—Patients administered midodrine had an average of 7.3 more symptom free days than those who received placebo (95% confidence interval (CI) 4.6 to 9; p < 0.0001). Eleven patients reported a positive therapeutic response with midodrine (p = 0.002). All domains of quality of life showed improvement with midodrine, in particular physical function (8.1; 95% CI 3.7 to 12.2), energy and vitality (14.6; 95% CI 7.3 to 22.1), and change in health status (22.2; 95% CI 11 to 33.4 ). Fourteen patients who were given placebo had tilt induced syncope compared with six given midodrine (p = 0.01). Baseline supine systolic blood pressure was higher and heart rate lower in patients who received midodrine than in those who were given placebo ( p < 0.05). A lower thoracic fluid index in patients administered midodrine indicates increased venous return when supine and during head up tilt. There were no serious adverse effects.
Conclusions—Midodrine had a conspicuous beneficial effect on symptom frequency, symptoms during head up tilt, and quality of life. Midodrine is recommended for the treatment of neurocardiogenic syncope in patients with frequent symptoms.

Keywords: midodrine;  neurocardiogenic syncope;  head up tilt test     

Magnesium causes nitric oxide independent coronary artery vasodilation in humans

OBJECTIVE—To determine how magnesium affects human coronary arteries and whether endothelium derived nitric oxide (EDNO) is involved in the coronary arterial response to magnesium.
DESIGN—Quantitative coronary angiography and Doppler flow velocity measurements were used to determine the effects of the nitric oxide synthase inhibitor N^G-monomethyl-L-arginine (L-NMMA) on magnesium induced dilation of the epicardial and resistance coronary arteries.
SETTING—Hiroshima University Hospital a tertiary cardiology centre.
PATIENTS—17 patients with angiographically normal coronary arteries.
INTERVENTIONS—Magnesium sulfate (MgSO₄) (0.02 mmol/min and 0.2 mmol/min) was infused for two minutes into the left coronary ostium before and after intracoronary infusion of L-NMMA.
MAIN OUTCOME MEASURES—Diameter of the proximal and distal segments of the epicardial coronary arteries and coronary blood flow.
RESULTS—At a dose of 0.02 mmol/min, MgSO₄ did not affect the coronary arteries. At a dose of 0.2 mmol/min, MgSO₄ caused coronary artery dilation (mean (SEM) proximal diameter 3.00 (0.09) to 3.11 (0.09) mm; distal 1.64 (0.06) to 1.77 (0.07) mm) and increased coronary blood flow (79.3 (7.5) to 101.4 (9.9) ml/min, p < 0.001 v baseline for all). MgSO₄ increased the changes in these parameters after the infusion of L-NMMA (p < 0.001 v baseline).
CONCLUSIONS—Magnesium dilates both the epicardial and resistance coronary arteries in humans. Furthermore, the coronary arterial response to magnesium is dose dependent and independent of EDNO.


Keywords: coronary artery; coronary blood flow; magnesium sulfate; nitric oxide     

Beneficial haemodynamic effects of insulin in chronic heart failure

OBJECTIVE—To characterise the central and regional haemodynamic effects of insulin in patients with chronic heart failure.
DESIGN—Single blind, placebo controlled study.
SETTING—University teaching hospital.
PATIENTS—Ten patients with stable chronic heart failure.
INTERVENTIONS—Hyperinsulinaemic euglycaemic clamp and non-invasive haemodynamic measurements.
MAIN OUTCOME MEASURES—Change in resting heart rate, blood pressure, cardiac output, and regional splanchnic and skeletal muscle blood flow.
RESULTS—Insulin infusion led to a dose dependent increase in skeletal muscle blood flow of 0.36 (0.13) and 0.73 (0.14) ml/dl/min during low and high dose insulin infusions (p < 0.05 and p < 0.005 v placebo, respectively). Low and high dose insulin infusions led to a fall in heart rate of 4.6 (1.4) and 5.1 (1.3) beats/min (p < 0.05 and p < 0.005 v placebo, respectively) and a modest increase in cardiac output. There was no significant change in superior mesenteric artery blood flow.
CONCLUSION—In patients with chronic heart failure insulin is a selective skeletal muscle vasodilator that leads to increased muscle perfusion primarily through redistribution of regional blood flow rather than by increased cardiac output. These results provide a rational haemodynamic explanation for the apparent beneficial effects of insulin infusion in the setting of heart failure.


Keywords: blood flow; heart failure; insulin; muscle     

Prognostic significance of cardiac 123I metaiodobenzylguanidine imaging for mortality and morbidity in patients with chronic heart failure: a prospective study

OBJECTIVE—To determine whether cardiac iodine-123 metaiodobenzylguanidine (¹²³I MIBG) imaging is useful in predicting the prognosis of patients with chronic heart failure.
DESIGN—Cardiac ¹²³I MIBG imaging was done on entry to the study. The cardiac MIBG washout rate was calculated from anterior chest view images obtained 20 and 200 minutes after injection of the isotope. Study patients were divided into two groups with washout rates above and below 27% (the mean value + 2 SD obtained in 20 normal subjects), and were then followed up.
SETTING—Tertiary referral centre.
PATIENTS—79 patients with chronic heart failure in whom the left ventricular ejection fraction was less than 40%.
RESULTS—There were 37 patients in group 1 (washout rate of  27%) and 42 in group 2 (< 27%). During a follow up period of between 1 and 52 months, eight patients died suddenly and five died of worsening heart failure in group 1, while none died in group 2; 13 patients in group 1 and four in group 2 were admitted to hospital for progressive heart failure. Kaplan-Meier analysis showed that group 1 had a significantly higher mortality and morbidity (p = 0.001 and p < 0.001, respectively) than group 2.
CONCLUSIONS—Cardiac ¹²³I MIBG washout rate seems to be a good predictor of prognosis in patients with chronic heart failure.


Keywords: chronic heart failure; sudden death; cardiac adrenergic nerve activity     

The left ventricular dysfunction questionnaire (LVD-36): reliability, validity, and responsiveness

OBJECTIVE—To examine the reliability, validity, and responsiveness of a new health status measure (LVD-36) for patients with left ventricular dysfunction which was designed with emphasis on content validity, clarity, brevity, and ease of use.
DESIGN—At baseline, patients completed the LVD-36 and a range of measures reflecting general health and disease severity. The LVD-36 was repeated after one week. After six months, it was repeated again, along with a transition question to measure global changes in health.
SETTING—Patients were recruited from the cardiology and general medical clinics at a south west London hospital.
PATIENTS—60 patients with chronic left ventricular dysfunction.
INTERVENTIONS—None.
MAIN OUTCOME MEASURES—Short form 36 questionnaire (SF-36), Minnesota living with heart failure questionnaire (LIhFE), New York Heart Association criteria, and exercise performance and echocardiographic tests.
RESULTS—The LVD-36 showed good internal consistency (κ = 0.95) and repeatability (r_i = 0.95). Its scores were significantly associated with SF-36 mental and physical component scores (r = −0.48 and −0.75; p < 0.0001), with exercise capacity (r = −0.52; p < 0.0001), and with systolic shortening fraction (r = −0.27; p < 0.05). Change in the LVD-36 over six months was associated with change in overall health (F = 5.7; p < 0.001). In tests of validity and responsiveness, the LVD-36 performed similarly to or marginally better than the LIhFE.
CONCLUSIONS—The LVD-36 showed a high level of reliability and validity, and appears to measure changes in health. It provides a short, simple, valid, and reliable measure of health status in patients with left ventricular dysfunction.


Keywords: health status; quality of life; heart failure; left ventricular dysfunction     

Abnormal ventricular activation and repolarisation during dobutamine stress echocardiography in coronary artery disease

Objective—To assess possible ECG changes caused by dobutamine stress and their relation to wall motion disturbances in patients with coronary artery disease.
Design—Prospective recording and analysis of 12 lead ECG at rest and during each stage of dobutamine stress echocardiography, and correlation with wall motion changes.
Setting—A tertiary referral centre for cardiac disease equipped with non-invasive facilities for pharmacological stress tests.
Subjects—27 patients, mean (SD) age 60 (8) years, with documented evidence of coronary artery disease in whom dobutamine stress echo was clinically indicated, and 17 controls of similar age.
Results—In controls, all ECG intervals shortened with increasing heart rate but in the patient group only PR and QT intervals shortened while QRS duration broadened and QTc interval prolonged progressively. In the 27 patients, 16 developed chest pain, 15 with reduced left ventricular long axis systolic excursion (p < 0.001), and all showed reduced peak lengthening rate; ST segment shift appeared in 16, 13 of whom developed chest pain, but did not correlate with reduction of either systolic long axis excursion or peak lengthening rate; QRS duration broadened in 20, 16 with reduction of long axis excursion (p < 0.02) which was more often seen at the septum (p < 0.005); QTc interval prolonged in 19, all of whom had associated reduction of peak long axis lengthening rate (p < 0.02).
Conclusions—QRS duration and QTc interval both normally shorten with dobutamine stress, while in coronary artery disease they both lengthen: changes in QRS duration correlate with systolic and QTc interval with diastolic left ventricular wall motion disturbances. ST segment shift also occurred in most patients, but without consistent correlation with wall motion abnormalities. It was thus less discriminating than the other two abnormalities in this respect.

Keywords: long axis;  QRS duration;  QTc interval;  stress echocardiography;  coronary artery disease     

Predictive value of dobutamine echocardiography and positron emission tomography in identifying hibernating myocardium in patients with postischaemic heart failure

Objective—To compare the predictive value of dobutamine echocardiography (DE) and positron emission tomography (PET) in identifying reversible chronic left ventricular (LV) dysfunction (hibernating myocardium) in patients with coronary artery disease (CAD) and overt heart failure.
Patients—30 patients (four women) with CAD and heart failure undergoing coronary artery bypass grafting (CABG).
Methods—Myocardial viability was assessed with DE (5 and 10 µg/kg/min) and PET with [¹⁸F] 2-fluoro-2-deoxy-D-glucose (FDG) under hyperinsulinaemic euglycaemic clamp. Regional (echo) and global LV function (MUGA) were assessed at baseline and six months after CABG.
Results—192 of the 336 (57%) dysfunctional LV segments improved function following CABG (hibernating) and the LV ejection fraction (EF) increased from 23(7) to 32(9)% (p < 0.0001) (in 17 patients > 5%). DE and PET had similar positive predictive values (68% and 66%) in the identification of hibernating myocardium, but DE had a significantly lower negative predictive value than PET (54% v 96%; p < 0.0001). A significant linear correlation was found between the number of PET viable segments and the changes in EF following CABG (r = 0.65; p = 0.0001). Stepwise logistic regression identified the number of PET viable segments as an independent predictor of improvement in EF > 5%, whereas the number of DE viable segments, the baseline LVEF, and wall motion were not.
Conclusions—DE has a higher false negative rate than PET in identifying recoverable LV dysfunction in patients with severe postischaemic heart failure. The amount of PET viable myocardium correlates with the functional outcome following CABG.

Keywords: dobutamine echocardiography;  positron emission tomography;  coronary artery disease;  heart failure;  hibernating myocardium     

Autonomic modulation of the atrial cycle length by the head up tilt test: non-invasive evaluation in patients with chronic atrial fibrillation

Objective—To determine the effects of upright posture compared with supine position on the dominant atrial cycle length (DACL) in patients with chronic atrial fibrillation.
Design—The power/frequency spectrum of QRST suppressed lead V1 ECG was studied in 14 patients in the supine position and during the head up tilt table test. The DACL changes were compared with changes in heart rate and blood pressure.
Results—Compared with the supine position, the upright position reduced the DACL from 160 to 150 ms (p < 0.01). The DACL was increased after returning to the supine position from the upright position, from 147 to 154 ms (p < 0.01). Heart rate increased from 91 beats/min in the supine position to 106 in the upright position (p < 0.01). There was a decrease in heart rate from 109 beats/min in the upright position to 93 after returning to the supine position (p < 0.01). No significant changes were seen in systolic or diastolic blood pressure. There were indications of an inverse relation between DACL and heart rate when comparing the supine position before and after tilt with the upright position (p < 0.001).
Conclusions—The sympathetic stimulation and vagal withdrawal induced by rising to upright body position are associated with a decrease in DACL during chronic atrial fibrillation. Thus a reflex increase in sympathetic discharge after induction of atrial fibrillation could favour the persistence of the arrhythmia.

Keywords: atrial fibrillation;  autonomic nervous system;  atrial cycle length;  heart rate     

Monocyte expression of tissue factor and adhesion molecules: the link with accelerated coronary artery disease in patients with chronic renal failure

Objective—To investigate the expression of monocyte tissue factor (MTF) and adhesion molecules in patients with chronic renal failure (CRF) and to look for any correlation with thrombin generation and Lp(a) lipoprotein.
Design—A study of MTF expression and adhesion molecules, prothrombin fragments 1+2 (PTf1+2), an index of thrombin generation, and lipoproteins in patients with CRF and in normal control subjects.
Background—Patients with end stage renal failure have an increased risk of coronary artery disease despite advances in therapy. Stimulated monocytes are potent activators of blood coagulation through the generation of MTF, which was recently implicated in the aetiology of acute coronary ischaemic syndromes.
Methods—MTF expression and adhesion molecules were measured in whole blood using immunofluorescence of monocytes labelled with anti-tissue factor antibody and CD11b and c by flow cytometry. PTf1+2 and Lp(a) lipoprotein in plasma were measured by enzyme linked immunosorbent assay (ELISA).
Patients—70 patients with CRF without documented coronary artery disease (30 patients with CRF undialysed, 20 patients undergoing chronic ambulatory peritoneal dialysis (CAPD), and 20 undergoing haemodialysis (HD)), together with 20 normal controls, were studied.
Results—The (mean (SD)) increased MTF of CRF (48.0 (29) v 33.3 (7.2) mesf unit/100 monocytes in controls, p = 0.04) was more pronounced in patients undergoing dialysis (HD 73.1 (32.8) (p < 0.003) and CAPD 62.8 (28.9) mesf unit/100 monocytes, p < 0.04). MTF activity showed a positive correlation with both PTf1+2 and serum creatinine (p < 0.003) but not with Lp(a) lipoprotein. Lp(a) lipoprotein was significantly increased in both dialysis groups compared with controls (p < 0.005) and non-dialysis CRF groups (p < 0.02). Monocyte adhesion molecule (CD11b) was significantly higher in all three CRF groups than in the controls (p = 0.006).
Conclusion—This study has demonstrated a hypercoagulable state in patients with CRF. This was especially pronounced in the dialysis patients. These findings provide a possible explanation for the increased cardiovascular and cerebrovascular morbidity and mortality in these patients.

Keywords: chronic renal failure; haemodialysis; continuous ambulatory dialysis; monocyte tissue factor; monocyte adhesion molecules; prothrombin; Lp(a) lipoprotein     

Efficacy of a new balloon catheter for internal cardioversion of chronic atrial fibrillation without anaesthesia

Objective—To compare a new internal cardioversion system incorporated into a balloon guided catheter with a conventional two electrode system in patients with atrial fibrillation (AF).
Design—Prospective study.
Patients—74 patients with chronic AF treated by internal cardioversion.
Materials—A 7.5 F balloon catheter with high energy electrode arrays each consisting of six 0.5 cm platinum rings. Brachial vein access enables one electrode array to be placed in the left pulmonary artery (distal pole) and the other at the lateral right atrial wall (proximal pole). The conventional two electrode system consists of 6 F electrodes placed in the proximal left pulmonary artery (anode) and the lower right atrium.
Interventions—Internal cardioversion was performed by shocks delivered in 40 V incremental steps from an external defibrillator. Shocks were applied by the new device to 32 patients (group A) and by the conventional sysytem to 42 patients (group B).
Results—The groups differed with respect to system positioning (9.2 (7.3) v 12.3 (8.1) minutes, p < 0.05) and fluoroscopy times (1.7 (1.0) v 3.3 (2.1) minutes, p < 0.01). Sinus rhythm was restored in 30 patients of group A and in 39 of group B (NS) with mean (SD) energy requirements of 8.4 (3.1) J and 7.2 (3.1) J, respectively (NS).
Conclusions—This new method of internal cardioversion has comparably high primary success rates and low sedation requirements with single and two lead systems.

Keywords: atrial fibrillation;  catheter;  defibrillation;  internal cardioversion