Abnormal vascular responses in human chronic cardiac failure are both endothelium dependent and endothelium independent

Objective—To study underlying vascular responses in chronic heart failure in patients without ACE inhibitor treatment, and to compare them with age matched controls.
Design—Forearm blood flow was studied using venous occlusion plethysmography in patients with chronic heart failure (n = 12) and matched controls (n = 13), after infusion of L-NMMA (a nitric oxide synthase inhibitor), glyceryl trinitrate (an endothelium independent vasodilator), and serotonin (an endothelium dependent vasodilator).
Results—L-NMMA produced significant vasoconstriction in normal subjects (forearm blood flow reduced by 24%), but not in patients (6%; difference between groups p < 0.03). The vasodilator responses to glyceryl trinitrate were impaired in patients (p < 0.02). In normal controls, serotonin produced initial dilatation, followed by vasoconstriction at high doses. In patients, no vasodilator responses were observed, only late vasoconstriction (p < 0.03).
Conclusions—The vascular responses of patients are confirmed as being abnormal. The lack of response to L-NMMA suggests that nitric oxide does not contribute to basal vascular tone in patients with chronic heart failure. The responses to glyceryl trinitrate and to serotonin suggest that there is both smooth muscle and endothelial dysfunction in patients with chronic heart failure.

Keywords: heart failure;  endothelium;  nitrates;  serotonin     

Angiotensin II modulates cardiovascular autonomic control in the absence of baroreflex loading

Objective—To investigate the effects of angiotensin II in the absence of baroreflex activation.
Design—Ten healthy male volunteers were studied in a single blind, randomised, crossover study of heart rate variability during intravenous angiotensin II infusion (5-20 ng/kg/min) compared with a control pressor infusion of phenylephrine (0.7-2.8 µg/kg/min). Each infusion was titrated to increase mean blood pressure by 20 mm Hg; sodium nitroprusside was then infused simultaneously to restore blood pressure to baseline values.
Results—During concomitant angiotensin II (AII) and sodium nitroprusside (SNP) infusion, the mean (SD) RR interval (864 (117) ms) was significantly shorter than during phenylephrine (PE) and sodium nitroprusside infusion (1057 (163) ms), and was significantly shorter than at baseline (999 (164) ms), despite comparable levels of blood pressure. Values of high frequency heart rate variability measured in the time and frequency domains were significantly lower during AII/SNP infusion than during PE/SNP: percentage of successive RR interval differences exceeding 50 ms, 30(16)% v 57(21)%; root mean square of successive RR interval differences, 63 (39) v 90 (40) ms; high frequency power 0.48 (0.19) v 0.66 (0.26) nu.
Conclusions—When the pressor response is controlled by sodium nitroprusside, angiotensin II infusion is associated with tachycardia. Analysis of heart rate variability suggests that this reflects inhibition of cardiac vagal activity.

Keywords: angiotensin II;  heart rate variability;  autonomic nervous system;  parasympathetic nervous system     

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     

Resetting of the cardiopulmonary baroreflex 10 years after surgical repair of coarctation of the aorta

OBJECTIVE—To characterise cardiopulmonary baroreflex responses and examine the effects of a 45 minute cycling bout late after successful repair of coarctation of the aorta.
SUBJECTS—10 young adults (mean (SEM) age 18.1 (2.6 years)) operated on for coarctation of the aorta 12.7 (3.5) years earlier, and 10 healthy controls.
DESIGN—Forearm blood flow (venous occlusion plethysmography) and vascular resistance, left ventricular internal diastolic diameter, and central venous pressure estimated from an antecubital vein were measured in the supine position at baseline and during five minute applications of lower body negative pressure (LBNP) at −15 mm Hg (LBNP₋₁₅) and −40 mm Hg (LBNP₋₄₀). Venous samples were obtained at baseline and during LBNP₋₄₀ for noradrenaline (norepinephrine), adrenaline (epinephrine), renin activity, and aldosterone. The tests were repeated after 45 minutes of moderate exercise.
RESULTS—Baseline heart rate (78 (9) v 64 (6) beats/min), echocardiographic cardiac output (6.9 (1.1) v 5.0 (0.2) l/min), shortening fraction (41.7 (1.8)% v 33.3 (1.3)%), and forearm blood flow (3.4 (0.4) v 2.3 (0.3) ml/100 g/min) were higher in the coarctation group than in the controls (p < 0.05). Changes in forearm blood flow and forearm vascular resistance from baseline to LBNP₋₄₀ were similar in both groups, but the relation between forearm vascular resistance and estimated central venous pressure or left ventricular internal diastolic diameter was shifted downward in the coarctation group. Plasma adrenaline was increased in the coarctation group (baseline: 3.2 (0.6) v 2.4 (0.3) pmol/l in controls; LBNP₋₄₀: 687 (151) v 332 (42) pmol/l) (p < 0.05). Both groups showed a similar downward displacement of forearm vascular resistance (p < 0.05) after exercise.
CONCLUSIONS—There appears to be resetting of the cardiopulmonary baroreflex to a lower forearm vascular resistance in young adults operated on for coarctation of the aorta, associated with hyperdynamic left ventricular function. Raised circulating adrenaline could contribute to the lower forearm vascular resistance.


Keywords: coarctation of aorta; cardiopulmonary baroreflex; forearm vascular resistance; circulating catecholamines     

Treatment of pulmonary hypertension with the continuous infusion of a prostacyclin analogue, iloprost

Objective—To compare prostacyclin with an analogue, iloprost, in treatment of severe pulmonary hypertension.
Patients—Eight patients with severe pulmonary hypertension: primary in five, thromboembolic pulmonary hypertension in three.
Methods—All patients underwent right heart catheterisation. Mean (SEM) right atrial pressure was 9.9 (2.2) mm Hg, mean pulmonary artery pressure 67.4 (3.0) mm Hg, cardiac index 1.75 (0.13) l/min/m² and mixed venous oxygen saturation 59.1(3.1)%. Continuous intravenous epoprostenol (prostacyclin, PGI₂) or iloprost was given for phase I (three to six weeks); the patients were then crossed over to receive the alternate drug in an equivalent phase II.
Main outcome measures—Exercise tolerance was measured at baseline and at the end of phase I and II with a 12 minute walk; distance covered, rest period, percentage drop in arterial oxygen saturation (ΔSaO₂%) and percentage rise in heart rate (ΔHR%).
Results—Walking distance covered rose from (mean (SEM)) 407.5 (73) to 591 (46) m with PGI₂ (p = 0.004) and to 602.5 (60) m while on iloprost (p = 0.008). Rest period decreased from 192 (73) seconds at baseline to 16 (16) seconds with PGI₂ (p = 0.01) and to 58 (34) seconds with iloprost (p = 0.008). ΔHR% was 37.5(6)% at baseline, 35(3)% on PGI₂, and 24(6)% on iloprost (p = 0.04).
Conclusions—Both intravenous PGI₂ and iloprost caused significant improvement in exercise tolerance. Iloprost offers an alternative to PGI₂ treatment of severe pulmonary hypertension.

Keywords: prostacyclin;  vasodilatation;  iloprost;  pulmonary hypertension     

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     

Autonomic control of the cerebral circulation during normal and impaired peripheral circulatory control

OBJECTIVE—To determine whether oscillations in the cerebrovascular circulation undergo autonomic modulation in the same way as cardiovascular oscillations.
DESIGN—Cardiovascular and cerebrovascular oscillations were monitored at rest and during sympathetic stimulation (head up tilt). The association with and transmission of the oscillations in the sympathetic (low frequency, LF) and respiratory (high frequency, HF) bands was assessed.
SUBJECTS—13 healthy volunteers, 10 subjects with vasovagal syncope, and 12 patients with complicated non-insulin dependent diabetes mellitus.
MAIN OUTCOME MEASURES—Power spectrum analysis of cerebral blood flow velocity, arterial blood pressure, and heart rate. Coherence analysis was used to study the association between each pair of oscillations. Phase analysis showed the delay of the oscillations in the cardiovascular signals with respect to the cerebrovascular signals.
RESULTS—The power in the sympathetic (LF) components in all the oscillations increased during head up tilt (p < 0.01) in the controls and in the subjects with vasovagal syncope, but not in patients with diabetes. Significant coherence (> 0.5) in the LF band was present between cerebrovascular and cardiovascular oscillations in most of the controls and in subjects with vasovagal syncope, but not in the diabetic patients (< 50% of the patients). In the LF band, cerebrovascular oscillations preceded the cardiovascular oscillations (p < 0.05) at rest in all groups: the phase shifts were reduced (p < 0.05) during head up tilt for all cardiovascular signals in healthy and syncopal subjects, but only for heart rate in diabetic patients.
CONCLUSIONS—The cerebrovascular resistance vessels are subject to autonomic modulation; low frequency oscillations in cerebral blood flow velocity precede the resulting fluctuations in other cardiovascular signals. Autonomic neuropathy and microvascular stiffness in diabetic patients reduces this modulation.


Keywords: autonomic nervous system; cerebral circulation; syncope; diabetes mellitus     

Intrapulmonary arteriovenous shunting may be a universal phenomenon in patients with the superior cavopulmonary anastomosis: a radionuclide study

OBJECTIVE—To evaluate the extent of intrapulmonary right to left shunting in children after bidirectional cavopulmonary anastomosis (BCPA).
DESIGN—Prospective study of patients who underwent BCPA in a single centre.
PATIENTS—17 patients with complex cyanotic congenital cardiac malformations who underwent BCPA at 1-45 months of age (median 21 months) were evaluated 15-64 months postoperatively (median 32 months). Five children between 1 and 10 years (median 5 years) with normal or surgically corrected intracardiac anatomy and peripheral pulmonary circulation who required V/Q scanning for other reasons were used as controls.
INTERVENTIONS—All patients underwent cardiac catheterisation to exclude angiographically demonstrable venovenous collaterals followed by pulmonary perfusion scanning using ^99mtechnetium (^99mTc) labelled albumen microspheres to quantify the intrapulmonary right to left shunt.
MAIN OUTCOME MEASURE—Percentage of intrapulmonary right to left shunt.
RESULTS—The mean (SD) level of physiological right to left shunting found in the control group was 5.4 (2.3)%. All patients with BCPA showed the presence of a significantly higher level of intrapulmonary shunting (26.8 (16.9)%, p < 0.001). The degree of shunting was significantly increased in the subgroup of 11 patients with BCPA as the only source of pulmonary blood flow (34.9 (15.8)%), when compared to the six remaining patients with an additional source of pulmonary blood supply (12.0 (2.6)%, p < 0.001). There was a negative correlation between age at BCPA and the shunt percentage found in the patients with a competitive source of pulmonary blood flow (r = −0.63, p < 0.01).
CONCLUSIONS—Intrapulmonary right to left shunting develops in all patients following BCPA. This may be caused by a sustained and inappropriate vasodilatation resulting from absence or decreased levels of a substance that inhibits pulmonary vasodilatation. Augmenting BCPA with an additional source of blood flow containing hepatic factor limits the degree of intrapulmonary arteriovenous shunting and may help provide successful longer term palliation.


Keywords: congenital heart defects; cavopulmonary anastomosis; pulmonary arteriovenous malformations; radionuclide scan     

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     

Ventricular mass and diastolic function in patients infected by the human immunodeficiency virus

OBJECTIVE—Echocardiographic and Doppler analysis of myocardial mass and diastolic function in patients infected with HIV.
DESIGN—Case-control study.
SETTING—Tertiary referral centre, Huelva, Spain.
PATIENTS—61 asymptomatic patients with HIV infection and 32 healthy controls.
MAIN OUTCOME MEASURES—Time motion, cross sectional, and Doppler echocardiographic studies were performed, and left ventricular mass and diastolic function variables determined (peak velocity of early and late mitral outflow and isovolumic relaxation time).
RESULTS—Left ventricular mass index (LVMI) was decreased in patients compared with healthy controls (mean (SD): 76.7 (23.6) v 118.8 (23.5) g/m², p < 0.001). Linear regression analysis showed a correlation between LVMI and brachial fat and muscle areas. The ratio of peak velocities of early and late mitral outflow was decreased in HIV infected patients compared with controls (1.19 (0.44) v 1.58 (0.38), p < 0.001). This ratio was exclusively related to haemodynamic variables (heart rate, systolic and diastolic blood pressures). HIV infected patients had a prolonged isovolumic relaxation time (103.0 (10.5) v 72.9 (12.9) ms, p < 0.001). Isovolumic relaxation time was correlated only with brachial muscle area on multivariate analysis.
CONCLUSIONS—HIV infected patients had a reduced left ventricular mass index and diastolic functional abnormalities. These cardiac abnormalities are predominantly related to nutritional status.


Keywords: HIV infection; cardiac function; nutrition     

Endogenous endothelin maintains coronary artery tone by endothelin type A receptor stimulation in patients undergoing coronary arteriography

OBJECTIVE—To examine the contribution of endothelin type A (ET_A) receptor stimulation by endogenously generated endothelin-1 (ET-1) to the maintenance of coronary vascular tone in humans.
DESIGN—Controlled clinical study.
SETTING—Tertiary cardiovascular referral centre.
PATIENTS—14 subjects were studied, seven with normal coronary arteries and seven with coronary artery disease, mean (SEM) age, 53 (2) years.
INTERVENTIONS—After diagnostic coronary arteriography, BQ-123 (a selective ET_A receptor antagonist; 100 nmol/min) in 0.9% saline, was infused into the left coronary artery at a rate of 1 ml/min for 60 minutes. Eight control subjects received saline alone.
MAIN OUTCOME MEASURES—Blood flow velocity in the left anterior descending coronary artery, measured using a Doppler flow guidewire; coronary arteriography performed at baseline and immediately at the end of the BQ-123 or saline infusion to measure the diameter of proximal and distal left anterior descending coronary artery segments.
RESULTS—The diameter of the proximal segment increased by 6 (2)%, while that of the distal segment increased by 12 (3)% after BQ-123 (both p < 0.05 v baseline). Coronary blood flow increased from 75 (10) to 92 (10) ml/min and coronary vascular resistance decreased from 1.99 (0.36) to 1.44 (0.22) mm Hg/ml/min after BQ-123 (both p < 0.05 v baseline). The response to BQ-123 of patients with and without coronary artery disease was similar. There was no effect of saline in the controls.
CONCLUSIONS—Endogenously produced ET-1 contributes to the maintenance of basal coronary artery tone in humans by ET_A receptor stimulation. The role of ET_B receptors remains to be defined.


Keywords: endothelins; arteries; blood flow; coronary circulation; angiography     

Changes in pulmonary artery size before and after total cavopulmonary connection

Objective—To assess changes in size of the central pulmonary arteries following a total cavopulmonary connection (TCPC).
Design—A retrospective analysis of the angiographic diameters of the central pulmonary arteries, expressed as z scores, in infancy before the TCPC and 3.5 (0.9) years (mean (SD)) later. Analysis of the relation between the pulmonary arteriolar resistance and the z scores at follow up.
Setting—Tertiary referral centre.
Patients—32 patients who had TCPC from February 1990 to July 1993.
Results—The patients were divided into two groups (n = 16) depending on their preoperative flow ratio: group I, Qp/Qs  1; group II, Qp/Qs > 1. At the initial study in infancy the mean z scores in group I were −6.0 for the right pulmonary artery (RPA) and −9.6 for the left pulmonary artery (LPA); in group II the respective values were −2.7 and −3.0. Before the TCPC the values increased to 0.5 (RPA) and −0.5 (LPA) in group I, and to 8.8 (RPA) and 8.2 (LPA) in group II. At follow up the z scores decreased to −2.4 (RPA) and −4.9 (LPA) in group I, and to 2.2 (RPA) and −0.7 (LPA) in group II. The changes in pulmonary artery diameters were significant for both groups (p < 0.02). Following the TCPC, no significant difference in pulmonary arteriolar resistance index was found between patients with relatively small pulmonary arteries (z score RPA+LPA  0) and those with relatively large pulmonary arteries (z score RPA+LPA > 0).
Conclusions—Creation of a TCPC results in a significant reduction in size of the central pulmonary arteries. At a mean interval of 3.5 years following the TCPC, however, there was no significant difference in pulmonary arteriolar resistance index between patients with smaller and larger central pulmonary arteries.

Keywords: total cavopulmonary connection;  congenital heart disease;  pulmonary artery size;  pulmonary arteriolar resistance     

Pulmonary vascular-bronchial interactions: acute reduction in pulmonary blood flow alters lung mechanics

BACKGROUND—Postoperative pulmonary hypertension in children after congenital heart surgery is a risk factor for death and is associated with severe acute changes in both pulmonary vascular resistance and lung mechanics.
OBJECTIVE—To examine the impact of changes in pulmonary blood flow on lung mechanics in preoperative children with congenital heart disease, in order to assess the cause-effect relation of pulmonary vascular-bronchial interactions.
DESIGN—Prospective, cross sectional study.
SETTING—Cardiac catheterisation laboratory, general anaesthesia with mechanical ventilation.
INTERVENTIONS—Variation of pulmonary blood flow (Qp) by either balloon occlusion of an atrial septal defect before interventional closure, or by complete occlusion of the pulmonary artery during balloon pulmonary valvuloplasty for pulmonary valve stenosis.
MAIN OUTCOME MEASURES—Ventilatory tidal volume (Vt), dynamic respiratory system compliance (Cdyn), respiratory system resistance (Rrs).
RESULTS—28 occlusions were examined in nine patients with atrial septal defect (median age 9.5 years) and 22 in eight patients with pulmonary stenosis (median age 1.2 years). Normalisation of Qp during balloon occlusion of atrial septal defect caused no significant change in airway pressures and Rrs, but there was a small decrease in Vt (mean (SD): 9.61 (0.85) to 9.52 (0.97) ml/kg; p < 0.05) and Cdyn (0.64 (0.11) to 0.59 (0.10) ml/cm H₂O*kg; p < 0.01). These changes were more pronounced when there was complete cessation of Qp during balloon valvuloplasty in pulmonary stenosis, with a fall in Vt (9.71 (2.95) to 9.32 (2.84) ml/kg; p < 0.05) and Cdyn (0.72 (0.29) to 0.64 (0.26) ml/cm H₂O*kg; p < 0.001), and there was also an increase in Rrs (25.1 (1.7) to 28.8 (1.6) cm H₂O/litre*s; p < 0.01). All these changes exceeded the variability of the baseline measurements more than threefold.
CONCLUSIONS—Acute changes in pulmonary blood flow are associated with simultaneous changes in lung mechanics. While these changes are small they may represent a valid model to explain the pathophysiological impact of spontaneous changes in pulmonary blood flow in clinically more critical situations in children with congenital heart disease.


Keywords: pulmonary blood flow; lung mechanics; catheter intervention; cardiopulmonary interaction     

Triggers of daily life ischaemia

Objective—To determine the usual triggers of silent and symptomatic ischaemia.
Design—Patients wore an ambulatory recorder for 48 hours. The device emitted a tone on detection of ischaemia and patients noted activities, feelings, and symptoms so that ischaemia could be attributed to one of four triggers: physical stress, mental stress, combined physical/mental stress, or no stressor.
Setting—Home environment.
Patients—Patients (n = 38) with stable coronary disease, positive exercise electrocardiography, and ischaemic episodes on ambulatory electrocardiography.
Main outcome measure—Matching ischaemic episodes with perceived triggers.
Results—Altogether 257 ischaemic episodes (53% silent) were documented. Triggers were: physical stress, 56%; mental stress, 5%; combined physical/mental stress, 8%; no identifiable trigger, 31%. Episodes associated with mental or no stress were more often silent (69% and 75%, respectively) than those associated with physical stress (45%, p < 0.01), while combined physical/mental stress episodes were usually symptomatic (10% silent, p < 0.01 v other stressors). Although physical stress was less commonly a trigger of silent ischaemia than angina (47% v 65%, p < 0.01), it was still the predominant trigger of silent ischaemia. There was no identifiable trigger in 45% of silent and only 17% of anginal episodes (p < 0.01). Only nine silent episodes involved mental stress alone as a trigger.
Conclusions—Daily life ischaemia is usually triggered by physical activity. Mental stress alone is an uncommon trigger of either silent or symptomatic ischaemia, while combined physical/mental stress is a significant but minor trigger of angina. Patients can identify a trigger in 83% of anginal episodes, compared with only half of silent ischaemic episodes.

Keywords: silent ischaemia;  ambulatory electrocardiography     

Lipophilic versus hydrophilic β1 blockers and the cardiac sympatho-vagal balance during stress and daily activity in patients after acute myocardial infarction

Objective—To compare the effects of a lipophilic and a hydrophilic β₁ blocker on cardiac sympatho-vagal balance during daytime activity and stress in patients four to six weeks after myocardial infarction.
Design—Randomised, double blind, crossover study comparing the effect of atenolol (50 mg once daily) with metoprolol CR (100 mg once daily) with treatment periods of four weeks.
Setting—Large teaching hospital.
Patients—50 patients (45 male, 5 female, age range 40 to 75 years), four to six weeks after an acute myocardial infarction.
Methods—At the end of each treatment period the 24 hour heart rate variability, heart rate variability power spectra during head up tilt and mental stress, baroreflex sensitivity, and exercise performance were evaluated.
Results—During daytime activity and during orthostatic and mental stress, both heart rate and the ratio between the low and high frequency spectral components of the heart rate variability were significantly lower with atenolol. Conversely, there was no difference between treatments in baroreflex sensitivity and resting plasma catecholamines. Exercise duration and peak oxygen consumption did not differ between treatments, but the heart rate during submaximal and peak exercise was significantly lower with atenolol.
Conclusions—At the doses used in this study, atenolol achieved greater β₁ adrenergic blockade than metoprolol CR and this was associated with significant inhibition of vagal withdrawal during stress. This suggests that peripheral blockade of β₁ adrenergic receptors may be more important than central blockade in preventing stress induced vagal withdrawal in patients after myocardial infarction.

Keywords: adrenergic receptors;  myocardial infarction;  stress;  baroreceptors     

Secondary prevention in coronary heart disease: a randomised trial of nurse led clinics in primary care

Objective—To evaluate whether nurse run clinics in general practice improve secondary prevention in patients with coronary heart disease.
Design—Randomised controlled trial.
Setting—A random sample of 19 general practices in northeast Scotland.
Patients—1173 patients (685 men and 488 women) under 80 years with working diagnoses of coronary heart disease, but without terminal illness or dementia and not housebound.
Intervention—Nurse run clinics promoted medical and lifestyle aspects of secondary prevention and offered regular follow up.
Main outcome measures—Components of secondary prevention assessed at baseline and one year were: aspirin use; blood pressure management; lipid management; physical activity; dietary fat; and smoking status. A cumulative score was generated by counting the number of appropriate components of secondary prevention for each patient.
Results—There were significant improvements in aspirin management (odds ratio 3.22, 95% confidence interval 2.15 to 4.80), blood pressure management (5.32, 3.01 to 9.41), lipid management (3.19, 2.39 to 4.26), physical activity (1.67, 1.23 to 2.26) and diet (1.47, 1.10 to 1.96). There was no effect on smoking cessation (0.78, 0.47 to 1.28). Of six possible components of secondary prevention, the baseline mean was 3.27. The adjusted mean improvement attributable to intervention was 0.55 of a component (0.44 to 0.67). Improvement was found regardless of practice baseline performance.
Conclusions—Nurse run clinics proved practical to implement in general practice and effectively increased secondary prevention in coronary heart disease. Most patients gained at least one effective component of secondary prevention and, for them, future cardiovascular events and mortality could be reduced by up to a third.

Keywords: coronary heart disease;  secondary prevention;  randomised controlled trial;  nurse led clinics     

Homocysteine and coronary heart disease in the Caerphilly cohort: a 10 year follow up

OBJECTIVE—Prospective assessment of the risk of coronary heart disease associated with total serum homocyst(e)ine (homocysteine) concentration.
DESIGN—Nested case-control study.
SETTING—Caerphilly and surrounding villages in south Wales, UK.
PARTICIPANTS—2290 men who participated in phase II of the study in 1984. After a mean follow up of 10 years, 312 men developed coronary heart disease and were compared with 1248 randomly selected, age frequency matched controls.
MAIN OUTCOME MEASURE—Acute myocardial infarction or death from coronary heart disease.
RESULTS—The geometric mean serum homocysteine concentration was higher in cases (12.2 µmol/l, 95% confidence interval (CI) 11.8 to 12.6 µmol/l) than in controls (11.8 µmol/l, 95% CI 11.3 to 12.5 µmol/l) (p = 0.09). There was a graded increase in the odds ratio of coronary heart disease across quintiles of the homocysteine concentration distribution compared with the first (p = 0.04), which was attenuated when adjusted for confounding variables (p = 0.4). There was a small but non-significant increase in the adjusted odds ratio of coronary heart disease per standard deviation change in the log distribution of homocysteine concentration (OR = 1.07 (95% CI .93 to 1.24), p = 0.34). Comparing the top quintile of the homocysteine concentration with the remaining 80%, the adjusted odds ratio of coronary heart disease was 1.03 (95% CI 0.73 to 1.45) (p = 0.8) and comparing the top 5% with the remaining 95% it was 1.05 (95% CI 0.56 to 1.95) (p = 0.9).
CONCLUSIONS—These findings do not support the hypothesis that a raised homocysteine concentration is a strong independent risk factor for coronary heart disease. Randomised controlled trials of homocysteine lowering treatment such as folic acid are needed before generalising the early positive results of observational studies.


Keywords: homocysteine; coronary heart disease; cohort     

Clinical and morphological characteristics in Streptococcus bovis endocarditis: a comparison with other causative microorganisms in 177 cases

Aim—To compare the clinical and morphological characteristics of patients with Streptococcus bovis endocarditis with those of patients with endocarditis caused by other microorganisms.
Methods—177 consecutive patients (Streptococcus bovis, 22; other streptococci, 94; staphylococci, 44; other, 17) with definite infective endocarditis according to the Duke criteria were included. All patients underwent transthoracic and transoesophageal echocardiography. In 88 patients, findings from surgery/necropsy were obtained.
Results—S bovis endocarditis was associated with older patients, with a higher mortality (p = 0.04), and with a higher rate of cardiac surgery (p < 0.001) than other microorganisms, although embolic events were observed less often (p = 0.02). Pathological gastrointestinal lesions were detected in 45% of the patients. Multiple valves were affected in 68% of the patients with S bovis endocarditis and in 20% of those with other organisms (p < 0.001). Moderate or severe regurgitation occurred more often in S bovis endocarditis than with other microorganisms (p = 0.05). When surgery or necropsy was performed, infectious myocardial infiltration of the left ventricle was confirmed histopathologically in 36% of the patients with S bovis endocarditis and in 10% of those with other organisms (p = 0.002).
Conclusions—S bovis endocarditis is a severe illness because of the more common involvement of multiple valves, and of the frequent occurrence of haemodynamically relevant valvar regurgitation and infectious myocardial infiltration.

Keywords: infective endocarditis;  Streptococcus bovis;  transoesophageal echocardiography;  valvar disease     

Relation between bradycardia dependent long QT syndrome and QT prolongation by disopyramide in humans

Background—Recent molecular biological investigations have identified abnormal genes in familial forms of long QT syndrome, but in bradycardia dependent acquired long QT syndrome, no such genetic abnormality has yet been identified.
Objective—To investigate the relation between the responses of QT interval to pacing change and to disopyramide.
Methods—This study included 13 patients with bradyarrhythmia who had undergone pacemaker implantation. The patients were divided into two groups: group I (n = 8), patients with QT prolongation (QT interval  500 ms) during bradycardia; group II (n = 5), patients without QT prolongation (QT interval < 500 ms) during bradycardia. The responses of QT interval caused by the change of pacing rate were determined and compared with the changes of the QT interval after disopyramide administration.
Results—The QT interval in group I was significantly longer than that in group II when the pacing rate was decreased from 110 to 50 beats/min: mean (SD) 451 (16) v 416 (17) ms at 90 beats/min (p = 0.0033), and 490 (19) v 432 (18) ms at 70 beats/min (p = 0.0002), respectively. The QT interval was prolonged significantly by disopyramide in both groups, but the change was more pronounced in group I than in group II: 78 (33) v 35 (10) ms (p < 0.05).
Conclusions—This study suggests that the patients showing bradycardia dependent QT prolongation are also more markedly affected by disopyramide and that abnormal potassium channel may be the underlying mechanism.

Keywords: bradycardia;  long QT syndrome;  disopyramide     

Predicting the effect of D,L-sotalol on ventricular tachycardia inducibility from the RR variability response

AIM—To find a rapid way of identifying non-responders to D,L-sotalol in patients with ventricular tachycardia.
METHODS—Programmed ventricular stimulation and RR variability were studied in the control state and 10 days after treatment with 160 to 320 mg of D,L-sotalol in 36 consecutive patients with ventricular tachycardia.
RESULTS—In 14 patients (group I) D,L-sotalol suppressed ventricular tachycardia inducibility. In 22 patients (group II) sustained ventricular tachycardia remained inducible during D,L-sotalol treatment. The ventricular tachycardia rate was slowed in eight patients and unchanged or accelerated in 14. At baseline, heart rate variability was similar in both groups. During treatment with D,L-sotalol, variables reflecting parasympathetic activity (pNN50, rMSSD, and high frequency amplitude (HF)) increased in both groups: HF increased from (mean (SD)) 75 (68) to 146 (134) in group I (p < 0.05) and from 60 (49) to 125 (79) in group II (p < 0.05). Other variables were unchanged in group I. In group II, the variables associated with sympathetic activity (coefficient of variance (CV), ratio of low frequency amplitude (LF) to HF) decreased significantly: CV decreased from 13 (4) to 9 (2) (p < 0.001) and LF/HF from 4.74 (3.02) to 3.00 (2.02) (p < 0.05).
CONCLUSIONS—The β blocking effect of D,L-sotalol produced a significant improvement over control values in indices of parasympathetic tone in all treated patients. However, the heart rate variability indices related to sympathetic activity were decreased only in non-responders. This effect of D,L-sotalol on heart rate variability could help detect non-responders to the drug and avoid an electrophysiological study.


Keywords: sotalol; ventricular tachycardia; heart rate variability