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     

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     

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     

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     

Effects of L- and D-arginine on the basal tone of human diseased coronary arteries and their responses to substance P

OBJECTIVE: To assess the effects of substance P administration alone and in combination with L- and D-arginine in patients with normal angiograms and in patients with coronary artery disease. DESIGN: Intracoronary infusions of (a) normal saline, (b) the receptor mediated nitric oxide stimulant substance P (5.6 and 27.8 pmol/min) before and after L- or D-arginine (50 and 150 micromol/min), and (c) glyceryl trinitrate (250 microg bolus) were given to 17 patients with coronary artery disease and stable angina, and to six patients with normal angiograms. The diameter of angiographically normal proximal and distal segments and coronary stenoses were measured by computerised quantitative angiography. RESULTS: L-arginine administration was associated with significant dilatation of stenoses (p < 0.01) of proximal segments of both "normal" (p < 0.05) and diseased (p < 0.01) arteries, and of distal segments of diseased arteries (p < 0.01). No significant changes were associated with D-arginine administration. Dose dependent dilatation of all segments including stenoses, was observed with substance P both before and after L-arginine infusion (p < 0.01). The magnitude of dilatation of stenoses and all segments of both "normal" and diseased coronaries was greater after L-arginine (p < 0.05) but not D-arginine and substance P infusion, than it was after saline and substance P infusion. Administration of D- or L-arginine did not change the magnitude of substance P induced dilatation. CONCLUSIONS: Diseased and "normal" coronary arteries dilated in response to substance P and L-arginine but were unaffected by D-arginine infusion. The magnitude of the response to substance P was not increased by L-arginine administration, indicating that it is not critically dependent on the availability of substrate for nitric oxide synthase.     

Transthoracic ultrasonic visualisation of coronary aneurysm, stenosis, and occlusion in Kawasaki disease

OBJECTIVE—To determine the sensitivity and specificity of our transthoracic echocardiographic technique using high frequency (7.5 MHz) transducers for identification of the presence and type of coronary artery disease in patients with Kawasaki disease.
DESIGN—The results of the prospective echocardiographic study in each of seven segments of the four major coronary arteries were compared with the selective coronary angiograms.
SETTING—Kitasato University Hospital.
SUBJECTS—60 patients with Kawasaki disease, ranging in age from 8.0 months to 22 years (median, 6.0 years).
RESULTS—Adequate echocardiographic images were obtained in 397 (95%) of 420 coronary segments. Coronary angiography showed the presence of coronary aneurysms in 87 segments and stenosis or occlusion in 28. The overall sensitivity and specificity of cross sectional echocardiography for correctly identifying coronary aneurysms were 95% and 99%, respectively; for correctly identifying coronary stenosis or occlusion the values were 85% and 98% for the right coronary artery, and 80% and 97% for the left anterior descending coronary artery. Agreement on the presence or absence of coronary aneurysms and obstructive lesions on echocardiograms between the two observers was 1.0 and 0.98, respectively.
CONCLUSIONS—Echocardiography may provide a non-invasive means of identifying the presence and type of coronary artery disease in patients with Kawasaki disease.


Keywords: Kawasaki disease; coronary artery aneurysm; coronary artery stenosis; echocardiography     

Effect of cholesterol lowering treatment on positive exercise tests in patients with hypercholesterolaemia and normal coronary angiograms

AIM—To assess the impact of cholesterol lowering on positive exercise stress tests in hypercholesterolaemic patients with normal coronary angiograms.
METHODS—43 non-diabetic patients aged 43-61 years, with total serum cholesterol concentrations of more than 7.75 mmol/l, positive exercise tests, and normal coronary angiograms, were started on the American Heart Association step 1 diet. After 12 weeks these patients were randomly assigned to treatment for another 16 weeks with the diet alone (diet group, n = 20) or with the diet plus lovastatin or simvastatin (statin group, n = 23). After this 28 week run in period, statins were withdrawn and lipid profile tests and exercise tests were done and repeated 20 weeks later.
RESULTS—At week 28, the statin group but not the diet group had significant reductions from baseline (week 12) in plasma total cholesterol (p < 0.0001), low density lipoprotein (p < 0.0001), and triglyceride (p < 0.0001). The number of patients with positive exercise tests decreased from 23 to three in the statin group and from 20 to 15 in the diet group (p = 0.01). After the final 20 weeks without statins, lipid profiles returned to baseline levels in all 17 patients remaining in the statin group, and exercise tests were again positive in 15 of these patients.
CONCLUSIONS—In hypercholesterolaemic patients with normal coronary arteries, cholesterol lowering treatment reduces myocardial ischaemia, as shown by the beneficial effects on exercise testing.


Keywords: hypercholesterolaemia; exercise stress testing; myocardial ischaemia; endothelium     

Magnetic resonance imaging of the coronary arteries: clinical results from three dimensional evaluation of a respiratory gated technique

BACKGROUND—Magnetic resonance coronary angiography is challenging because of the motion of the vessels during cardiac contraction and respiration. Additional challenges are the small calibre of the arteries and their complex three dimensional course. Respiratory gating, turboflash acquisition, and volume rendering techniques may meet the necessary requirements for appropriate visualisation.
OBJECTIVE—To determine the diagnostic accuracy of respiratory gated magnetic resonance imaging (MRI) for the detection of significant coronary artery stenoses evaluated with three dimensional postprocessing software.
METHODS—32 patients referred for elective coronary angiography were studied with a retrospective respiratory gated three dimensional gradient echo MRI technique. Resolution was 1.9 × 1.25 × 2 mm. After manual segmentation three dimensional evaluation was performed with a volume rendering technique.
RESULTS—Overall 74% (range 50% to 90%) of the proximal and mid coronary artery segments were visualised with an image quality suitable for further analysis. Sensitivity and specificity for the detection of significant stenoses were 50% and 91%, respectively.
CONCLUSIONS—Volume rendering of respiratory gated MRI techniques allows adequate visualisation of the coronary arteries in patients with a regular breathing pattern. Significant lesions in the major coronary artery branches can be identified with a moderate sensitivity and a high specificity.


Keywords: magnetic resonance imaging; coronary artery disease; coronary angiography; computer assisted image processing     

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     

Three dimensional intravascular ultrasonic assessment of the local mechanism of restenosis after balloon angioplasty

OBJECTIVE—To assess the mechanism of restenosis after balloon angioplasty.
DESIGN—Prospective study.
PATIENTS—13 patients treated with balloon angioplasty.
INTERVENTIONS—111 coronary subsegments (2 mm each) were analysed after balloon angioplasty and at a six month follow up using three dimensional intravascular ultrasound (IVUS).
MAIN OUTCOME MEASURES—Qualitative and quantitative IVUS analysis. Total vessel (external elastic membrane), plaque, and lumen volume were measured in each 2 mm subsegment. Delta values were calculated (follow up − postprocedure). Remodelling was defined as any (positive or negative) change in total vessel volume.
RESULTS—Positive remodelling was observed in 52 subsegments while negative remodelling occurred in 44. Remodelling, plaque type, and dissection were heterogeneously distributed along the coronary segments. Plaque composition was not associated with changes in IVUS indices, whereas dissected subsegments had a greater increase in total vessel volume than those without dissection (1.7 mm³ v −0.33 mm³, p = 0.04). Change in total vessel volume was correlated with changes in lumen (p < 0.05, r = 0.56) and plaque volumes (p < 0.05, r = 0.64). The site with maximum lumen loss was not the same site as the minimum lumen area at follow up in the majority (n = 10) of the vessels. In the multivariate model, residual plaque burden had an influence on negative remodelling (p = 0.001, 95% confidence interval (CI) −0.391 to −0.108), whereas dissection had an effect on total vessel increase (p = 0.002, 95% CI 1.168 to 4.969).
CONCLUSIONS—The mechanism of lumen renarrowing after balloon angioplasty appears to be determined by unfavourable remodelling. However, different patterns of remodelling may occur in individual injured coronary segments, which highlights the complexity and influence of local factors in the restenotic process.


Keywords: balloon angioplasty; intravascular ultrasound; remodelling; restenosis     

Hypothetical ratings of coronary angiography appropriateness: are they associated with actual angiographic findings,mortality, and revascularisation rate? The ACRE study

OBJECTIVE—To determine whether ratings of coronary angiography appropriateness derived by an expert panel on hypothetical patients are associated with actual angiographic findings, mortality, and subsequent revascularisation in the ACRE (appropriateness of coronary revascularisation) study.
DESIGN—Population based, prospective study. The ACRE expert panel rated hypothetical clinical indications as inappropriate, uncertain, or appropriate before recruitment of a cohort of real patients.
SETTING—Royal Hospitals Trust, London, UK.
PARTICIPANTS—3631 consecutive patients undergoing coronary angiography (no exclusion criteria).
MAIN OUTCOME MEASURES—Angiographic findings, mortality (n = 226 deaths), and revascularisation (n = 1556 procedures) over 2.5 years of follow up.
RESULTS—The indications for coronary angiography were rated appropriate in 2253 (62%) patients. 166 (5%) coronary angiograms were performed for indications rated inappropriate, largely for asymptomatic or atypical chest pain presentations. The remaining 1212 (33%) angiograms were rated uncertain, of which 47% were in patients with mild angina and no exercise ECG or in patients with unstable angina controlled by inpatient management. Three vessel disease was more likely among appropriate cases and normal coronaries were more likely among inappropriate cases (p < 0.001). Mortality and revascularisation rates were highest among patients with an appropriate indication, intermediate in those with an uncertain indication, and lowest in the inappropriate group (log rank p = 0.018 and p < 0.0001, respectively).
CONCLUSION—The ACRE ratings of appropriateness for angiography predicted angiographic findings, mortality, and revascularisation rates. These findings support the clinical usefulness of expert panel methods in defining criteria for performing coronary angiography.


Keywords: coronary artery disease; coronary angiography; coronary artery bypass graft; appropriateness of coronary revascularisation     

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     

Increased serum concentrations of advanced glycation end products: a marker of coronary artery disease activity in type 2 diabetic patients

OBJECTIVE—To assess whether the concentrations of serum advanced glycation end products (AGE) in diabetic patients with obstructive coronary artery disease differ from those in type 2 diabetic patients without obstructive coronary artery disease.
DESIGN—Serum AGE concentrations were measured in type 2 diabetic patients and in non-diabetic patients, both with and without obstructive coronary artery disease, and the relation between these values and coronary disease severity was evaluated.
RESULTS—Mean (SD) serum AGE concentrations were higher (p < 0.0125) in type 2 diabetic patients with obstructive coronary artery disease (5.5 (2.5) mU/ml, n = 30) than in patients without obstructive coronary artery disease (2.8 (0.5) mU/ml, n = 12), and higher than in non-diabetic patients with (3.4 (1.0) mU/ml, n = 28) and without (3.2 (0.4) mU/ml, n = 13) obstructive coronary artery disease. Serum AGE was associated with the degree of coronary arteriosclerosis in type 2 diabetic patients with obstructive coronary artery disease (single vessel: n = 13, 3.4 (0.9) mU/m; two vessel: n = 6, 5.7 (1.6) mU/m; three vessel: n = 11, 7.2 (2.5) mU/ml). Serum AGE was positively correlated with serum mean four year HbA_1C (r = 0.46, p < 0.01), but not with recent serum HbA_1C (r = 0.24). The four groups did not differ in the other coronary risk factors.
CONCLUSIONS—Serum AGE concentrations may be associated with long term poor glycaemic control and reflect the severity of coronary arteriosclerosis in type 2 diabetic patients.


Keywords: advanced glycation end products; non-insulin dependent diabetes; coronary artery disease     

Monosomy 22q11 in patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries

Objective—To describe the morphology of the pulmonary arteries in patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries with and without monosomy 22q11.
Design—A retrospective analysis of all patients with this congenital heart defect who are being followed at the University Children's Hospital Erlangen.
Setting—A tertiary referral centre for paediatric cardiology and paediatric cardiac surgery.
Patients—21 patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries. Monosomy 22q11 was diagnosed by fluorescent in situ hybridisation using the D22S75 probe (Oncor). The morphology of the pulmonary arteries was assessed on the basis of selective angiograms.
Results—10 patients (48%) were shown to have a microdeletion in 22q11 (group I). There was no difference with respect to the presence of confluent central pulmonary arteries between these patients (80%) and the remaining 11 patients (group II) without monosomy 22q11 (91%). Patients of group I, however, more often had arborisation anomalies of the pulmonary vascular bed (90% in group I v 27% in group II). Because of the more severe abnormalities of the pulmonary arteries, a biventricular repair had not been possible in any of the children with monosomy 22q11, though repair had been carried out in 64% of the children in group II.
Conclusions—The developmental disturbance caused by monosomy 22q11 seems to impair the connection of the peripheral pulmonary artery segments to the central pulmonary arteries in patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries, resulting in a lower probability of biventricular repair.

Keywords: CATCH 22;  pulmonary atresia and ventricular septal defect;  major aortopulmonary collateral arteries;  conotruncal anomaly face syndrome     

Myocarditis mimicking acute myocardial infarction: role of endomyocardial biopsy in the differential diagnosis

OBJECTIVE—To test the hypothesis, using endomyocardial biopsies, that unexplained cases of apparent acute myocardial infarction were caused by myocarditis.
MATERIAL—Between 1992 and 1998, 12 patients were admitted to the coronary care unit with severe chest pain, ST segment elevation, increased serum creatine kinase and MB isoenzyme, and with wall motion abnormalities on echocardiogram highly suggestive of acute myocardial infarction. These patients were further investigated by endomyocardial biopsy, as their coronary angiograms were normal. A diagnosis of myocarditis was made according to the Dallas criteria. A panel of antibodies was used for immunohistochemical characterisation of inflammatory cell infiltrate. Polymerase chain reaction (PCR) was used to detect viral genomes in seven cases.
RESULTS—Haematoxylin and eosin staining of the endomyocardial biopsy showed active myocarditis in six patients and borderline myocarditis in one. Immunohistochemistry was positive for inflammatory cell infiltrates in 11 patients, including all the seven who were positive on haematoxylin and eosin staining according to the Dallas criteria. Only one patient had no evidence of inflammation. PCR was positive in two patients, both for Epstein-Barr virus. Follow up showed complete resolution of echocardiographic abnormalities in all patients except one.
CONCLUSIONS—Myocarditis can mimic acute myocardial infarction in patients with angiographically normal coronary arteries, leading to errors of treatment. In patients with apparent myocardial infarction and a normal coronary angiogram, endomyocardial biopsy may help in the diagnosis of myocarditis. The sensitivity of endomyocardial biopsy was enhanced by using immunohistochemical and molecular biological techniques.


Keywords: acute myocardial infarction; endomyocardial biopsy; myocarditis     

Relation between coronary artery remodelling (compensatory dilatation) and stenosis in human native coronary arteries

OBJECTIVES—To investigate the contribution of plaque size and vessel remodelling to coronary artery stenosis and to assess the role of vessel shrinkage (negative remodelling) across a wide range of lesions.
DESIGN—Postmortem study of coronary remodelling in perfusion fixed hearts.
SUBJECTS—24 men and 24 women who died suddenly with coronary artery disease.
MAIN OUTCOME MEASURES—Percentage stenosis, percentage plaque burden, percentage remodelling, and arc of normal vessel were measured and related to age, sex, smoking status, and history of hypertension.
RESULTS—There was a positive relation between percentage stenosis and percentage plaque burden (r = 0.6, p < 0.0001) and an inverse relation between percentage stenosis and percentage remodelling (r = -0.4, p < 0.0001). Multilinear regression modelling showed that luminal stenosis = 1.0 (plaque burden) − 0.4 (vessel remodelling). Remodelling was greater in lesions that would not have been significant at angiography ( 25% stenosis) than in the remaining lesions (25.9 (26)% v 10.0 (21.1)%, p < 0.0001, respectively) and was reduced in segments with circumferential plaques (12.7 (24.5)% v 20.7 (24.3)% in eccentric plaques, p = 0.001). Remodelling did not correlate with age, sex, or smoking. Negative remodelling was present in 62 lesions with a stenosis > 25% versus 10 lesions with  25% stenosis (p < 0.0001). Lesions with negative remodelling had greater plaque burden and luminal stenosis and a reduced arc of normal segment.
CONCLUSION—Outward arterial remodelling negates the stenosing effect of increasing plaque size. Significant coronary stenoses arise from a failure of this outward remodelling in the face of a large plaque burden. Coronary arterial remodelling is unrelated to sex or smoking and is plaque specific.


Keywords: coronary artery disease; vessel remodelling; pathology     

Hibernating myocardium: morphological correlates of inotropic stimulation and glucose uptake

BACKGROUND—In patients with postischaemic left ventricular dysfunction, segments recovering function after revascularisation (hibernating myocardium) may not respond during dobutamine echocardiography, despite preserved [¹⁸F] 2-fluoro-2-deoxy-D-glucose (FDG) uptake at positron emission tomography.
OBJECTIVE—To investigate whether this lack of response might reflect the degree of ultrastructural change in hibernating myocardium.
METHODS—Transmural biopsies were obtained from 22 dysfunctional segments in 22 patients during coronary artery bypass grafting and examined by light and electron microscopy. Wall motion scores and coronary vasodilator reserve were assessed before and after coronary artery bypass grafting (CABG).
RESULTS—Mean (SD) wall motion score improved in all segments following CABG (from 2.24 (0.4) to 1.55 (0.4); p < 0.0001), confirming hibernating myocardium. In these segments myocardial blood flow (positron emission tomography with H₂¹⁵O) before CABG was similar to that in normal volunteers (1.02 (0.24) v 1.02 (0.23) ml/min/g), while the coronary vasodilator reserve was blunted (1.26 (0.7) v 3.2 (1.6); p < 0.0001). Myocardial blood flow was unchanged after CABG, whereas coronary vasodilator reserve increased to 2.10 (0.90) (p < 0.0007). In hibernating myocardium myofibrillar loss, interstitial fibrosis, and glycogen-rich myocytes were more marked than in control donor hearts. On the basis of the response to dobutamine before CABG, two functional groups were identified: group A, segments with inotropic reserve (n = 15); group B, segments without inotropic reserve (n = 7). FDG uptake was similar in group A and group B (0.40 (0.1) v 0.44 (0.1) µmol/min/g). In group B there was more myofibrillar loss (26 (8)% v 11 (5)%; p = 0.0009) and glycogen-rich myocytes (28 (11)% v 17 (10)%; p = 0.02), whereas interstitial fibrosis, myocardial blood flow, and coronary vasodilator reserve were similar in the two groups. Myofibrillar loss was the only independent predictor of inotropic reserve (p = 0.01).
CONCLUSIONS—Hibernating myocardium is characterised by a reduced coronary vasodilator reserve which improves on revascularisation and shows a spectrum of ultrastructural changes that influence the response to dobutamine, while FDG uptake is invariably preserved.


Keywords: coronary artery disease; heart failure; myocardial viability; myocardial blood flow; positron emission tomography     

Nitrate induced coronary vasodilatation: differential effects of sublingual application by capsule or spray

Background—Sublingual nitroglycerin (glyceryltrinitrate, GTN) capsules or isosorbide dinitrate (ISDN) spray are routinely used to treat anginal attacks and to vasodilate maximally the epicardial coronary arteries during coronary angiography.
Objective—To compare the coronary vasodilatory effects of GTN capsules and ISDN spray with those induced by intracoronary GTN using quantitative coronary angiography.
Design—96 patients (79 men and 17 women; median age 59 years) were randomised to four groups to receive either a sublingual capsule containing 0.8 mg GTN or two puffs of spray delivering 0.8 mg ISDN, followed or preceded by an intracoronary bolus of 0.2 mg GTN used as reference for maximal vasodilatation.
Results—There was a significant increase in the mean diameter of coronary arteries in angiographically normal segments in patients who received either intracoronary GTN (groups 1 and 2) or ISDN spray (group 4) as a first application (group 1, 0.46 mm, +17%, (baseline vessel diameter 100%), p < 0.001; group 2, 0.45 mm, +13%, p < 0.001; group 4, 0.47 mm, +13%, p < 0.05). Patients who received a sublingual GTN capsule as the first application mode (group 3) had no significant change in epicardial vessel diameter (0.10 mm, +5%, p = 0.3).
Conclusions—Sublingual ISDN spray may be more efficacious than sublingual GTN capsules in certain patients with anginal attacks. ISDN spray should be preferred over capsules in coronary angiographic procedures.

Keywords: angiography;  isosorbide dinitrate;  nitroglycerin;  vasodilatation;  angina     

Coronary arterial anatomy in tetralogy of Fallot: morphological and clinical correlations

Objective—To clarify the problems in angiographic diagnosis of major coronary arteries crossing the right ventricular outflow tract.
Design—A retrospective study with clinicomorphological correlations to ascertain any aberrant coronary arteries and variations in distribution of the normal right coronary arterial branches.
Setting—Tertiary referral centre.
Subjects—36 necropsy specimens together with the aortograms and surgical reports from 130 patients with tetralogy of Fallot.
Results—A preventricular branch was found in 19% of cases with tetralogy of Fallot, but in none of 13 normal hearts. Aberrant origin of the anterior interventricular coronary artery was found in 14% of the specimens. The combination of "laid back" and straight lateral views, when reviewed retrospectively, identified this anomaly correctly in nine of 16 patients, with these findings confirmed at surgery in seven patients. A major branch initially thought to cross the outflow tract was shown retrospectively to be an infundibular artery in six, with surgical confirmation in four. It was a preventricular branch in another patient.
Conclusions—Using the laid back view alone, infundibular and preventricular branches may be mistaken for a major aberrant artery. A combination of laid back and straight lateral views is needed to avoid false positive diagnosis.

Keywords: angiography;  congenital heart defects;  tetralogy of Fallot;  paediatric cardiology     

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