A case-control investigation of the relation between hyperlipidaemia and calcific aortic valve stenosis

Objective—To investigate the relation of hyperlipidaemia to calcific aortic valve stenosis.
Design—A case-control study designed to detect a clinically relevant difference in the fasting plasma concentrations of total cholesterol between the groups at the 5% level with a power of 90%. Predefined subgroup analyses were based on presence of significant coronary disease and valve morphology (that is, bicuspid or tricuspid).
Setting—A district general hospital.
Subjects—20 patients with severe calcific aortic stenosis and 20 controls.
Results—Mean (SD) fasting plasma total cholesterol in patients with aortic stenosis was 0.79 (1.50) mmol/l greater than in the controls (p = 0.029). The magnitude of differences between patients with aortic stenosis and controls was similar whether the patients had coronary artery disease (0.78 (1.73) mmol/l) or not (0.80 (1.37) mmol/l). The presence of a stenosed tricuspid aortic valve was associated with a significant increase in plasma cholesterol (1.70 (0.87) mmol/l, p = 0.012). For bicuspid valves the degree of elevation of plasma cholesterol was less and not statistically significant.
Conclusions—Calcific aortic stenosis is associated with hypercholesterolaemia, especially when the valve is tricuspid. Further studies are necessary to confirm that the relation is causal. This finding may have implications for measures to prevent the most common cause of cardiac valve replacement in the developed world.

Keywords: calcific aortic stenosis;  hypercholesterolaemia;  hyperlipidaemia     

Sustained high pressure double balloon angioplasty of calcified conduits

Objective—To assess the efficacy of prolonged high pressure angioplasty for dilatation of calcified and stenotic cardiac conduits in children.
Design—A prospective study of consecutive patients presenting with calcified and stenotic conduits.
Setting—Two tertiary paediatric cardiology departments.
Methods—Sustained (up to five minutes), high pressure (up to 18 atmospheres), double balloon angioplasty was performed in six calcified and stenotic cardiac conduits (five consecutive patients, three male, two female, age 4 to 17 years). Four patients had right ventricle to pulmonary artery (RV-PA) conduits, and one had two venous conduits in a Fontan circulation.
Results—Marked reductions in right ventricle to pulmonary artery gradients, from a median (range) of 48 (40 to 62) mm Hg to 11 (5 to 16) mm Hg, and in right ventricle to femoral artery pressure ratios, from a median of 0.8 (0.72 to 0.86) to 0.4 (0.33 to 0.44), were achieved for all RV-PA conduits. All five patients had sustained clinical improvement at follow up (median follow up 12 months) and none has required reintervention or surgery.
Conclusions—Prolonged high pressure double balloon angioplasty may have a role in prolonging the interval between conduit replacements in a subset of patients with complex heart defects.

Keywords: angioplasty; conduit; calcification; congenital heart disease; interventional cardiology     

Hospital transfer for primary coronary angioplasty in high risk patients with acute myocardial infarction

OBJECTIVE—To investigate the feasibility, safety, and associated time delays of interhospital transfer in patients with acute myocardial infarction for primary percutaneous transluminal coronary angioplasty (PTCA).
DESIGN AND PATIENTS—Prospective observational study with group comparison in a single centre. 68 consecutive patients with acute myocardial infarction transferred for primary PTCA from other hospitals (group A) were compared with 78 patients admitted directly to the referral centre (group B).
MAIN OUTCOME MEASURES—Patient groups were analysed with regard to baseline characteristics, time intervals from onset of chest pain to balloon angioplasty, hospital stay, and follow up outcome.
RESULTS—Patients in group A presented with a higher rate of cardiogenic shock initially than patients in group B (25% v 6%, p = 0.01) and had been resuscitated more frequently before PTCA (22% v 5%, p = 0.01). No deaths or other serious complications occurred during interhospital transfer. Median transfer time was 63 (range 40-115) minutes for helicopter transport (median 42 (28-122) km, n = 14), and 50 (18-110) minutes by ground ambulance (median 8 (5-68) km, n = 54). The median time interval from the decision to perform coronary arteriography to balloon inflation was 96 (45-243) minutes in group A and 52 (17-214) minutes in group B (p = 0.0001). In transferred patients (group A) the transportation associated delay and the longer in-hospital median decision time (50 (10-1120) minutes in group A v 15 (0-210) minutes in group B, p = 0.002) concurred with a longer total period of ischaemia (239 (114-1307) minutes in group A v 182 (75-1025) minutes in group B, p = 0.02) since the beginning of chest pain. Success of PTCA (TIMI 3 flow in 95% of all patients), in-hospital mortality (7% v 9%, mortality for patients not in cardiogenic shock 0% v 4%), and follow up after median 235 days was similarly favourable in groups A and B, respectively. Only one hospital survivor (group A) died during follow up.
CONCLUSION—Interhospital transport for primary PTCA in high risk patients with acute myocardial infarction is safe and feasible within a reasonable period of time. Short and medium term outcome is favourable. Optimising the decision process and transport logistics may further improve outcome by reducing the total time of ischaemia.


Keywords: acute myocardial infarction; primary percutaneous transluminal coronary angioplasty; hospital transfer; time delay     

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 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     

Increased platelet reactivity and significant changes in coagulation markers after cavopulmonary connection

OBJECTIVE—To evaluate platelet reactivity and coagulation markers after surgical palliation of univentricular hearts.
DESIGN AND PATIENTS—Cross sectional survey of 24 patients, median age 11 (range 4-22) years, at 2 (range 0.5-6) years after a total cavopulmonary connection (TCPC; n = 14) or a bidirectional Glenn anastomosis (Glenn; n = 10).
MAIN OUTCOME MEASURES—Platelet reactivity and/or coagulation markers were measured in 20 patients (four excluded because of anticoagulant treatment) and compared with 33 healthy controls, median age 12 (range 6-16) years.
RESULTS—None of the patients had clinically apparent thromboembolic events. However, increased platelet reactivity was observed ex vivo both after collagen induced platelet aggregation (median 73% (interquartile range 61-84%) in patients, and 61% (47-69%) in controls; p < 0.01), and after ADP induced platelet aggregation (69% (53-77%) in patients, and 56% (40-66%) in controls; p < 0.05). Concentrations of protein S antigen, antithrombin III, and protein C activity were reduced after both TCPC and Glenn. A concomitant decrease was seen in coagulation factor II, VII, X, and factor VII clot activity.
CONCLUSIONS—Several abnormalities in the coagulation system were observed after bidirectional Glenn anastomosis, similar to alterations previously described in Fontan operated and TCPC patients. Antithrombotic treatment in these patients is still an unresolved issue, but aspirin is often recommended. This study shows that such a strategy is rational and the results suggest that antiplatelet treatment may be advantageous, either alone or in combination with oral anticoagulant treatment.


Keywords: Fontan procedure; thrombosis; platelets; coagulation     

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     

Transcatheter closure of atrial septal defects using the Cardio-Seal implant

OBJECTIVE—To review the outcomes of transcatheter closure of atrial septal defects using the Cardio-Seal implant.
DESIGN—A prospective interventional study.
SETTING—Tertiary referral centre.
PATIENTS—The first 50 patients (median age 9.7 years) who underwent attempted percutaneous occlusion.
INTERVENTIONS—Procedures were done under general anaesthesia and transoesophageal guidance between December 1996 and July 1998.
MAIN OUTCOME MEASURES—Success of deployment, complications, and assessment of right ventricular end diastolic diameter, septal wall motion, and occlusion status by echocardiography.
RESULTS—The median balloon stretched diameter was 14 mm. Multiple atrial septal defects were present in 11 patients (22%) and a deficient atrial rim (< 4 mm) in 19 (38%). In four patients (8%), a second device was implanted after removal of an initially malpositioned first implant. There were no significant immediate complications. All patients except one were discharged within 24 hours. At the latest follow up (mean 9.9 months) a small shunt was present in 23 patients (46%), although right ventricular end diastolic dimensions (mean (SD)) corrected for age decreased from 137 (29)% to 105 (17)% of normal, and septal motion abnormalities normalised in all but one patient. No predictors for a residual shunt were identified. Supporting arm fractures were detected in seven patients (14%) and protrusion of one arm through the defect in 16 (32%), the latter being more common in those with smaller anterosuperior rims. No untoward effects resulted from arm fractures or protrusion. There were no complications during follow up, although five patients (10%) experienced transient headaches.
CONCLUSIONS—The implantation of the Cardio-Seal device corrects the haemodynamic disturbances secondary to the right ventricular volume overload, with good early outcome.


Keywords: congenital heart disease; interventional catheterisation; atrial septal defects     

Effects of α tocopherol and β carotene supplements on symptoms, progression, and prognosis of angina pectoris

Objective—To evaluate the effects of α tocopherol and β carotene supplements on recurrence and progression of angina symptoms, and incidence of major coronary events in men with angina pectoris.
Design—Placebo controlled clinical trial.
Setting—The Finnish α tocopherol β carotene cancer prevention study primarily undertaken to examine the effects of α tocopherol and β carotene on cancer.
Subjects—Male smokers aged 50-69 years who had angina pectoris in the Rose chest pain questionnaire at baseline (n = 1795).
Interventions—α tocopherol (vitamin E) 50 mg/day, β carotene 20 mg/day or both, or placebo in 2 × 2 factorial design.
Main outcome measures—Recurrence of angina pectoris at annual follow up visits when the questionnaire was readministered; progression from mild to severe angina; incidence of major coronary events (non-fatal myocardial infarction and fatal coronary heart disease).
Results—There were 2513 recurrences of angina pectoris during follow up (median 4 years). Compared to placebo, the odds ratios for recurrence in the active treatment groups were: α tocopherol only 1.06 (95% confidence interval (CI) 0.85 to 1.33), α tocopherol and β carotene 1.02 (0.82 to 1.27), β carotene only 1.06 (0.84 to 1.33). There were no significant differences in progression to severe angina among the groups given supplements or placebo. Altogether 314 major coronary events were observed during follow up (median 5.5 years) and the risk for them did not differ significantly among the groups given supplements or placebo.
Conclusions—There was no evidence of beneficial effects for α tocopherol or β carotene supplements in male smokers with angina pectoris, indicating no basis for therapeutic or preventive use of these agents in such patients.

Keywords: antioxidants;  angina pectoris;  prevention;  vitamin supplements     

Haemochromatosis gene mutations in idiopathic dilated cardiomyopathy

BACKGROUND—Two common mutations of the haemochromatosis associated gene (HFE) (cys282tyr (C282Y) and his63asp (H63D)) have been implicated in haemochromatosis and as modulators in cardiovascular disease.
OBJECTIVE—To investigate the role of these mutations in the pathogenesis of idiopathic dilated cardiomyopathy.
DESIGN AND SETTING—Case-control and prospective cohort study of patients attending a cardiomyopathy unit in a tertiary referral cardiac centre.
METHODS—207 unrelated white patients with dilated cardiomyopathy, followed up for 259 patient years, and 200 controls were tested for HFE C282Y and H63D mutations by polymerase chain reaction and restriction digestion.
RESULTS—31/207 patients (15%) v 24/200 controls (12%) carried C282Y (adjusted odds ratio (OR) 1.2 (95% confidence interval 0.7 to 2.2)), 74/207 (36%) v 53/200 (27%) carried H63D (OR 1.6 (1.1 to 2.5)), and 10/207 (4.8%) v 4/200 (2%) were compound heterozygotes (OR 2.6 (0.8 to 8.5)). Four patients and six controls were H63D homozygous and one was C282Y homozygous. There was a progressive increase in mean serum iron ([Fe]) and transferrin saturations from patients with no mutation ([Fe] = 16.3 µmol/l, transferrin saturation = 23.7%) through H63D heterozygotes (17.5 µmol/l, 25.8%), C282Y heterozygotes (17.1 µmol/l, 26.6%), H63D homozygotes (20.0 µmol/l, 33.5%), compound heterozygotes (26.8 µmol/l, 41.7%), and C282Y homozygotes (34 µmol/l, 71%). At follow up (median 90 months) the rate of death or cardiac transplantation was 52/207 (25%). C282Y heterozygotes had less ventricular dilatation (mean (SD): 59.9 (1.7) mm v 64.9 (0.9) mm, p < 0.05), better fractional shortening (24 (1.7)% v 18.8 (1.4)%, p < 0.01), and a trend towards improved survival without transplantation. [Fe] and transferrin saturation did not correlate with disease severity and were not associated with reduced survival.
CONCLUSIONS—The frequency of the H63D mutation is significantly increased in patients with idiopathic dilated cardiomyopathy. As H63D has a relatively minor effect on iron status, the mechanism of this association may be unrelated to iron metabolism.


Keywords: dilated cardiomyopathy; genetics; haemochromatosis     

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     

Transcatheter closure of atrial septal defects in adults with the Amplatzer septal occluder

OBJECTIVE—To assess the efficacy and complications of device occlusion of atrial septal defects in adults, using the Amplatzer septal occluder (ASO).
DESIGN—A prospective interventional study.
SETTING—Paediatric cardiology departments in two European teaching hospitals.
PATIENTS—The first 20 patients accepted for atrial septal defect device occlusion, on the basis of transoesophageal echocardiography. Sixteen patients had larger defects with right heart dilatation, while the primary indication for closure in four was a history of early paradoxical embolism.
INTERVENTIONS—Transcatheter atrial septal defect occlusions performed under transoesophageal echocardiography and fluoroscopic guidance between December 1996 and June 1998.
OUTCOME MEASURES—Success of deployment of ASO devices, procedure and fluoroscopic times, complications, and symptoms.
RESULTS—The ASO device was successfully implanted in all 20 patients (14 female), median age 44.2 years, with no complications. Of the 16 patients with right heart dilatation, the median Qp:Qs was 2.5:1. Defects measured 11-22 mm (median 18) on transoesophageal echocardiography, with balloon sized diameter (and device size) of 13-28 mm (median 20). For all 20 patients, the procedure time ranged from 38-78 minutes (median 61), and fluoroscopy 8.4-24.7 minutes (median 15.2). There were residual shunts in three patients at the end of the procedure, which were trivial ( 1 mm) as assessed by transoesophageal echocardiography, and persisted for more than six months in only one patient. Follow up ranged from 0.1-1.5 years (median 0.7). There have been no late complications.
CONCLUSIONS—The ASO device can be used successfully to close selected oval fossa defects in adults, with minimal procedural morbidity and excellent early results.


Keywords: atrial septal defect; interventional cardiac catheterisation; Amplatzer septal occluder     

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     

β2 Adrenergic receptors mediate important electrophysiological effects in human ventricular myocardium

OBJECTIVE—To define the effects of β₂ adrenergic receptor stimulation on ventricular repolarisation in vivo.
DESIGN—Prospective study.
SETTING—Tertiary referral centre.
PATIENTS—85 patients with coronary artery disease and 22 normal controls.
INTERVENTIONS—Intravenous and intracoronary salbutamol (a β₂ adrenergic receptor selective agonist; 10-30 µg/min and 1-10 µg/min), and intravenous isoprenaline (a mixed β₁/β₂ adrenergic receptor agonist; 1-5 µg/min), infused during fixed atrial pacing.
MAIN OUTCOME MEASURES—QT intervals, QT dispersion, monophasic action potential duration.
RESULTS—In patients with coronary artery disease, salbutamol decreased QT_onset and QT_peak but increased QT_end duration; QT_onset-QT_peak and QT_peak-QT_end intervals increased, resulting in T wave prolongation (mean (SEM): 201 (2) ms to 233 (2) ms; p < 0.01). There was a large increase in dispersion of QT_onset, QT_peak, and QT_end which was more pronounced in patients with coronary artery disease—for example, QT_end dispersion: 50 (2) ms baseline v 98 (4) ms salbutamol (controls), and 70 (1) ms baseline v 108 (3) ms salbutamol (coronary artery disease); p < 0.001. Similar responses were obtained with isoprenaline. Monophasic action potential duration at 90% repolarisation shortened during intracoronary infusion of salbutamol, from 278 (4.1) ms to 257 (3.8) ms (p < 0.05).
CONCLUSIONS—β₂ adrenergic receptors mediate important electrophysiological effects in human ventricular myocardium. The increase in dispersion of repolarisation provides a mechanism whereby catecholamines acting through this receptor subtype may trigger ventricular arrhythmias.


Keywords: β₂ adrenergic receptors; ventricular repolarisation; QT dispersion; salbutamol; isoprenaline     

Increased concentrations of inflammatory mediators in unstable angina: correlation with serum troponin T

OBJECTIVE—To measure plasma interferon γ, monocyte chemotactic protein-1 (MCP-1), and interleukin 6 and to assess their correlation with cardiac troponin T in unstable angina.
DESIGN—Blood sampling in patients undergoing coronary arteriography for known or suspected ischaemic heart disease.
PATIENTS—76 patients divided in three groups: 29 with unstable angina (group 1), 28 with stable angina (group 2), and 19 without ischaemic heart disease and with angiographically normal coronary arteries (group 3).
MAIN OUTCOME MEASURES—Plasma interleukin 6, interferon γ, MCP-1, and troponin T in the three groups of patients.
RESULTS—Interleukin 6 was increased in group 1 (median 2.19 (range 0.53-50.84) pg/ml) compared with the control group (1.62 (0.79-3.98) pg/ml) (p < 0.005), whereas interferon γ was higher in group 1 (range 0-5.51 pg/ml) than in the other two groups (range 0-0.74 pg/ml and 0-0.37 pg/ml; p < 0.005 and p < 0.001, respectively). Patients with unstable angina (group 1) and positive troponin T had higher concentrations of interferon γ than those with negative troponin T (0-5.51 pg/ml v 0-0.60 pg/ml, p < 0.001). Plasma MCP-1 was also higher in group 1 (median 267 (range 6-8670) pg/ml) than in the other two groups (134 (19-890) pg/ml and 84.5 (5-325) pg/ml; p < 0.005 and p < 0.001, respectively), and among group 1 patients with a positive troponin T assay than in those with normal troponin T (531 (14.5-8670) pg/ml v 69 (6-3333) pg/ml; p < 0.01). There was no difference in plasma interleukin 6 in group 1 patients between those with and without raised troponin T.
CONCLUSIONS—The inflammatory cytokines interferon γ and MCP-1 are increased in patients with unstable angina, particularly in those with raised concentrations of troponin T, suggesting that they are probably related to myocardial cell damage or to plaque rupture and thrombus formation.


Keywords: inflammatory cytokines; troponin T; unstable angina     

An association between arterial pulse pressure and variation in the fibrillin-1 gene

Objective—To investigate whether variation in the fibrillin-1 gene was associated with blood pressure in healthy middle aged men, as had been observed in patients with abdominal aortic aneurysm.
Design, setting, and patients—Middle aged men (n = 245), aged 50 to 61 years, were recruited from one of the nine general practices participating in the second Northwick Park heart study. Blood samples were obtained for the preparation of genomic DNA and analysis of plasma variables.
Main outcome measures—Systolic, diastolic, and pulse pressures; fibrillin-1 genotype characterised with a four allele variable tandem nucleotide repeat polymorphism in intron 28.
Results—In healthy middle aged men only three common genotypes were observed: 2-2 (frequency 54.1%), 2-3 (16%), and 2-4 (15%). The mean arterial systolic (and pulse) pressure varied according to fibrillin-1 genotype: 2-4 genotype, 126.3 (47.6) mm Hg; 2-2 genotype, 131.0 (51.3) mm Hg; and 2-3 genotype, 135.5 (54.2) mm Hg. The median pulse pressure was 50 mm Hg. Distribution of men around the median pulse pressure, according to genotype, showed a significant trend for patients of 2-4 genotype to have the lowest pulse pressures, those of 2-2 genotype to have intermediate pressures, and those of 2-3 genotype to have the highest pulse pressures (p = 0.003 for healthy men).
Conclusions—There appears to be a significant association between fibrillin-1 genotype and arterial pulse pressure in men aged 50 to 61 years.

Keywords: blood pressure;  fibrillin;  pulse pressure     

Stent treatment for coarctation of the aorta: intermediate term follow up and technical considerations

OBJECTIVE—To report the initial and intermediate term results of stent implantation in children with coarctation of the aorta.
PATIENTS AND DESIGN—17 patients with coarctation of the aorta underwent stent implantation (median age 11 years, range 0.4-15 years); six were treated for isolated coarctation, nine for recurrent coarctation (five after surgical repair and four after balloon dilatation), and two for complex long segment coarctation.
INTERVENTIONS—The procedure was guided by a second catheter placed transseptally in the left ventricle or the aorta proximal to the coarctation site, for angiographic and haemodynamic monitoring during the procedure. Twenty two stents were implanted in 17 patients. One of the patients with long segment coarctation received four stents and the other three. Palmaz 4014 stents were placed in 11 patients, Palmaz 308 in five, and Palmaz 154 in one.
RESULTS—Immediately after stent implantation the peak systolic gradient (mean (SD)) fell from 50.0 (24.5) to 2.1 (2.4) mm Hg (p < 0.05). The diameter of the stenotic lesion increased from 5.1 (1.5) mm to 13.9 (2.4) mm (p < 0.05). There were no deaths or procedure related complications. At a median follow up of 33 months, no cases of recoarctation were identified, either clinically (0/17; 0%, 95% confidence interval (CI) 0% to 19%) or angiographically (0/13; 0%, 95% CI 0% to 25%).
CONCLUSIONS—Stent implantation for the treatment of coarctation of the aorta appears to have very low morbidity and mortality, and reasonable intermediate term results. Long term freedom from recoarctation using this method remains to be determined in comparison with simple balloon dilatation.


Keywords: aortic coarctation; blood vessel prostheses; stents     

Early therapeutic experience with the endothelin antagonist BQ-123 in pulmonary hypertension after congenital heart surgery

OBJECTIVE—To assess the effect of endothelin type A (ET_A) receptor antagonism in infants with pulmonary hypertension following corrective surgery for congenital heart disease.
DESIGN—Open label, preliminary study.
SETTING—Tertiary paediatric cardiothoracic surgical centre.
PATIENTS—Three infants (aged 3 weeks, 7 weeks, and 8 months) with postoperative pulmonary hypertension unresponsive to conventional treatment, including inhaled nitric oxide.
INTERVENTIONS—Patients received incremental intravenous infusions (0.1 to 0.3 mg/kg/h) of the ET_A receptor antagonist BQ-123.
MAIN OUTCOME MEASURES—The response to BQ-123 administration was determined using continuous invasive monitoring of cardiorespiratory variables.
RESULTS—BQ-123 infusion caused a reduction in the ratio of pulmonary to systemic pressures (0.62 (0.01) to 0.52 (0.03), mean (SEM)) with an accompanying decrease in right ventricular stroke work index (4.6 (0.4) to 2.5 (0.3) g/m) and a tendency for the cardiac index to rise (2.1 (0.2) to 2.7 (0.6) l/min/kg/m²). This was associated with a well tolerated fall in the arterial partial pressure of oxygen (16.5 (4.1) to 12.4 (3.3) kPa) and mean systemic arterial pressure (57 (3) to 39 (3) mm Hg).
CONCLUSIONS—ET_A receptor antagonism in infants with postoperative pulmonary hypertension after corrective surgery for congenital heart disease led to significant improvement in pulmonary haemodynamic indices. However, these benefits were associated with reductions in systemic blood pressure and arterial oxygen saturation, the latter consistent with a ventilation-perfusion mismatch. On the basis of these results, studies in pulmonary hypertension will need to proceed with caution.


Keywords: endothelin-1; pulmonary hypertension; receptor antagonism; congenital heart disease     

Dobutamine echocardiography predicts functional outcome after revascularisation in patients with dysfunctional myocardium irrespective of the perfusion pattern on resting thallium-201 imaging

OBJECTIVE—To evaluate whether the predictive value of dobutamine echocardiography for assessing contractile reserve was altered by differing patterns of regional myocardial perfusion.
PATIENTS—31 consecutive patients with symptomatic congestive heart failure (left ventricular ejection fraction < 35%) caused by coronary artery disease.
SETTING—A district general hospital.
METHODS—Thallium-201 perfusion imaging and low dose dobutamine (5-15 µg/kg/min) echocardiography were performed and resting echocardiography was repeated three months after revascularisation. Perfusion pattern and systolic wall thickening were compared using a 12 segment left ventricular model.
RESULTS—Of the 273 severely dysfunctional segments, 106 (39%) showed a normal perfusion and 167 (61%) an abnormal pattern. After revascularisation, recovery occurred in 71 of the segments with a normal perfusion pattern, and in these a dobutamine response was observed in 61 (86%); recovery also occurred in 56 segments with a mild to moderate abnormality of perfusion, and in these a dobutamine response was seen in 46 (81%) (NS). After revascularisation, the positive and negative predictive values for recovery of dysfunctional segments, where the majority were abnormally perfused, were 88% and 86%, respectively. Systolic wall thickening score indices improved from (mean (SD)) 3.21 (0.58) to 2.6 (0.66) (p < 0.001) after revascularisation in dobutamine responsive patients (n = 24) compared with patients who did not show a dobutamine response (2.86 (0.65) and 3.13 (0.56), p = 0.61, respectively).
CONCLUSIONS—Dobutamine echocardiography predicted improvement of dysfunctional myocardium after revascularisation irrespective of the resting perfusion pattern seen.


Keywords: dobutamine echocardiography; perfusion; revascularisation     

Low dose dobutamine echocardiography for predicting functional recovery after coronary revascularisation

OBJECTIVE—To evaluate the effects of chronic coronary occlusion on the accuracy of low dose dobutamine echocardiography in predicting recovery of dysfunctional myocardium after revascularisation.
DESIGN—Retrospective study.
SETTING—Tertiary referral centre.
PATIENTS—53 consecutive patients with  70% stenosis of the left anterior descending coronary artery (LAD) and regional ventricular dysfunction (group 1, non-occluded LAD; group 2, occluded LAD) who underwent dobutamine echocardiography.
INTERVENTIONS—26 patients underwent coronary artery bypass grafting and 27 had percutaneous transluminal coronary angioplasty.
MAIN OUTCOME MEASURES—Baseline studies before revascularisation included cross sectional echocardiography at rest and during dobutamine infusion (5-10 µg/kg/min), and coronary angiography. The dobutamine study was performed mean (SD) 35 (28) days before revascularisation. Echocardiography at rest was repeated 90 (48) days after revascularisation.
RESULTS—Of 296 dysfunctional segments, 63 in group 1 (43%; 63/146) and 69 in group 2 (46%; 69/150) (NS) improved at follow up. Mean (SD) regional wall motion score index decreased from 1.97 (0.48) (95% confidence interval (CI) 1.01 to 2.93) before revascularisation to 1.74 (0.52) (95% CI 0.70 to 2.78) at follow up in group 1 (p = 0.001), and from 2.12 (0.41) (95% CI 1.30 to 2.98) to 1.88 (0.36) (95% CI 1.16 to 2.60) in group 2 (p = 0.0006). In group 1, sensitivity (87% v 52%; p < 0.0001), negative predictive value (88% v 65%; p = 0.001), and accuracy (77% v 64%; p = 0.01) were all significantly higher than in group 2, despite the angiographic evidence of collaterals in patients with occluded vessels.
CONCLUSIONS—Dobutamine echocardiography shows reduced sensitivity in predicting recovery of dysfunctional myocardium supplied by totally occluded vessels. Thus caution should be used in selecting such patients for revascularisation on the basis of a viability assessment made in this way.


Keywords: dobutamine; coronary artery disease; viability; chronic occlusion