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Background: Expression of transforming growth factor-beta1 (TGF-beta1) is central to vascular repair due to its effects on smooth muscle cell, monocyte/macrophage, leucocyte, and extracellular matrix accumulation and proliferation. Genetic polymorphism at position +915 of the TGF-beta1 gene determines the degree of cytokine production in response to injury. We investigated this allelic variation on the development of cardiac transplant-related coronary vasculopathy (CV)., Methods: Using sequence-specific primers to the TGF-beta1 gene region of interest, a polymerase chain reaction (PCR) and gel electrophoresis identified the genotype in 129 cardiac transplant recipients. An association was sought between the presence of a high- (GG) or low/intermediate-producing (CC/GC) genotype and the development of coronary vasculopathy diagnosed by coronary angiography., Results: C allele carriers made up 10.9% of the recipient population but were significantly less likely to develop coronary vasculopathy (p = 0. 0361). Mean time to diagnosis was 1240.5 days in G homozygotes relative to 2266.5 days in C allele carriers (p = 0.002). Pre- and 1-year posttransplant clinical variables were equivalent between the 2 groups. Multivariate analysis identified the GG genotype (p = 0. 042, hazard ratio 3.01, [95% CI, 1.056-10.99]), donor age (p = 0.002, hazard ratio 1.063, [95% CI, 1.029-1.097]), and number of acute-rejection episodes of grade 3 or greater in the first year (p = 0.029, hazard ratio 1.11, [95% CI, 1.05-1.26]) as significant predictors of vasculopathy., Conclusion: This study demonstrates a correlation between a high-producing TGF-beta1 genotype and an earlier onset of cardiac-transplant coronary vasculopathy. This gives an important insight into the pathophysiology of cardiac transplant vasculopathy and suggests new treatment options.

Objective: To compare patient selection and outcome of coronary angioplasty procedures before and after the widespread availability and use of stents., Subjects and Methods: Group 1 consisted of 252 consecutive patients and group 2 comprised 389 patients who underwent angioplasty between April 1993 and March 1994, and April 1995 and March 1996, respectively, in a tertiary cardiothoracic centre. Clinical variables were collected before the procedures. Endpoints included in-hospital death, the need for repeat coronary angiography, repeat angioplasty, and coronary artery bypass surgery. Lesions were classified under American Heart Association/American College of Cardiology criteria in 100 randomly selected patients from each group., Results: 311 and 482 angioplasty procedures were performed in patients from groups 1 and 2, respectively. One or more stents were deployed in nine (4%) and 179 (46%, p < 0.01) patients, respectively. The success rate was higher in group 2 than in group 1 patients (483/523 (92%) v 274/372 (88%), respectively, p < 0.05). There were significantly more single vessel angioplasty procedures (198/252 (79%) v 272/389 (70%), p < 0.05), type A lesions (30/116 (26%) v 19/130 (15%), p < 0.05), patients with stable angina (220/252 (87%) v 311/389 (80%), p < 0.05), and fewer acute myocardial infarction patients (1/252 (0%) v 12/389 (3%), p < 0.05) treated in group 1 than in group 2, respectively. Similar numbers of angioplasty were performed in the left anterior descending, left circumflex, and right coronary arteries. There were no significant differences in the in-hospital mortality or the need for repeat coronary angiography, angioplasty, or bypass surgery at 24 hours or six months after the initial procedure., Conclusion: Patients undergoing angioplasty in the stenting era had features associated with an increased risk of complication. Despite this, the primary success rate was higher, and the complication rate and the need for subsequent revascularisation were similar in the two groups, supporting the widely held clinical impression that stenting has made a valuable impact on the practice of angioplasty.

Background: Raised pulmonary vascular resistance is associated with decreased survival after orthotopic heart transplantation and patients with this risk factor are usually denied transplantation. In a proportion of cases raised pulmonary vascular resistance may fall with time and medical treatment., Methods: Seven patients with high pulmonary vascular resistance (range 3.9-6.6 Wood units) at initial assessment for cardiac transplantation were restudied by right heart catheterisation after a period of seven to 17 months., Results: In five of the seven patients the pulmonary vascular resistance had fallen, allowing orthotopic heart transplantation to be performed in four. In one patient the resistance was static and in one it had risen. The mean fall in pulmonary vascular resistance for the group was (mean (SD)) 2.6 (2.7) Wood units, p < 0.05., Conclusion: Patients who have been denied transplantation on the basis of their raised pulmonary vascular resistance should be reassessed after four to six months if they remain otherwise clinically suitable.

In 60 consecutive patients undergoing vein graft surgery the angiographic appearances of the coronary vessels were compared with those of the vessels at operation. On the basis of lumen diameter at the potential sites for grafting it was possible to predict with reasonable accuracy from examination of the angiogram which vessels were large enough to be grafted. Angiographic predictive accuracy was 82% and was similar both for vessels which filled normally and for those which filled by collaterals. The predictive value of the angiographic assessment was similar for branches thought to be too small (predictive value 74%) and for those considered sufficiently large (predictive value 85%) to receive a vein graft. Disease of the vessel walls was found at surgery (66% of coronary branches examined) more frequently than was predicted from the angiographic appearances (33%). Previous necropsy studies have found a high prevalence of coronary atheroma in the population, yet normal angiographic appearances in the coronary arteries are not uncommon in patients undergoing investigation for suspected coronary disease. The present study showed that atheroma may be present in coronary vessels without encroaching into the vessel lumen, so that it is not evident on the angiogram. Coronary atheroma is thus present more often and is more widely distributed in the coronary tree than is indicated by coronary angiography.

The heart rate/ST slope was evaluated in 49 patients undergoing routine investigation for possible coronary artery disease. The slope correctly predicted the absence of any 75% stenoses in the seven patients to whom this applied; it was, however, correct for only four of 30 with one stenosis, one of 10 with two, and neither of the patients with three. Distinct slope ranges were not found, and the previously published ranges said to be specific for no significant stenosis and one, two, and three vessel disease were not.

Oesophageal function was assessed in 52 patients with angina pectoris whose coronary angiograms were completely normal and in 21 patients with angina pectoris who had significant coronary artery disease. During a standard oesophageal manometric study, abnormalities were found in 23 (44%) patients with normal coronary angiograms but in only 2 (10%) patients with coronary artery disease (p less than 0.01). Twenty-four (46%) patients with normal coronary angiograms were found to have gastro-oesophageal reflux disease during 24-hour oesophageal pH monitoring. Of the 52 patients with normal coronary angiograms, 19 (37%) had gastro-oesophageal reflux disease and abnormal oesophageal motility, 5 (10%) had gastro-oesophageal reflux disease alone, and 7 (13%) had oesophageal motility disorder alone. The use of provocation procedures, including intravenous edrophonium during oesophageal manometry and treadmill exercise testing during pH monitoring, enabled the oesophageal abnormality to be demonstrated simultaneously with chest pain in 25 of these 31 patients. Typical angina pectoris, coincident with abnormal oesophageal motility, was precipitated in a subgroup of patients who had been shown to have oesophageal manometric abnormalities and gastro-oesophageal reflux disease by the infusion of hydrochloric acid into the oesophagus; both the chest pain and manometric abnormality resolved following the oral administration of antacid.

The angiocardiographic and clinical findings in 218 patients with significant obstruction confined to the left anterior descending coronary artery were reviewed to study the influence of the site of obstruction and of the collateral circulation on clinical presentation and prognosis. One hundred and fifty-six patients had been managed medically, 51 had had aortocoronary bypass operations, and 11 had had left ventricular aneurysms excised. The artery was divided into three segments: left anterior descending 1 (LAD1) from its origin to the first septal branch, left anterior descending 2 (LAD2) from the first septal to the first diagonal branch, and left anterior descending 3 (LAD3) the remaining distal vessel. Cardiogenic shock occurred only in patients with LAD1 lesions, but apart from this the clinical presentation bore no consistent relation to the site of disease. Patients with proximal lesions were more likely to have a "positive" exercise test, had more severely impaired left ventricular function, and had a worse prognosis than those with more distal disease. Non-visualisation of collateral vessels in patients with left anterior descending occlusion was associated with extensive infarction, and patients who presented with infarction had more severely impaired ventricular function than those who presented with angina and subsequently had an infarction. Left ventricular function was poor at the time of angiography in 11 of 12 of those who subsequently died; it is therefore unlikely that the prognosis of patients with isolated left anterior descending obstruction could be improved by expanding the indication for aortocoronary bypass from that of severe angina.

Early and late outcome was studied in 630 patients who underwent aortic valve replacement between 1974 and 1982. Group 1 (506 patients) did not have important coronary artery disease, group 2 (69 patients) had coronary artery disease and underwent coronary artery bypass grafting, and group 3 (55 patients) had coronary artery disease but did not undergo myocardial revascularisation. Early mortality (within 30 days of operation) was significantly lower for group 1 (6%) than for group 2 (13%) and for group 3 (16%). Operative mortality in all three groups was lower in patients operated on more recently. The three year survival of patients in group 1 (83%) was significantly higher than that of patients in group 3 (62%) but not than that of patients in group 2 (76%). The findings of this study suggest that the presence of coronary artery disease increases the risk of aortic valve replacement whether or not coronary artery grafting is performed. Myocardial revascularisation, however, seems to return patients with aortic valve and coronary artery disease to a survival curve similar to that of patients with isolated aortic valve disease.

We compared Hexabrix 320 (580 mOsm kg-1) with Conray 420 (2500 mOsm kg-1) for left ventriculography using a prospective randomised double-blind protocol. One hundred consecutive patients with suspected coronary disease were assigned to Hexabrix (52) or Conray (48) for left ventriculography (dose 10 ml m-2 BSA; flow rate 12 ml s-1). Thirteen patients found Hexabrix unpleasant compared with 24 receiving Conray; overall the feelings of warmth and discomfort were less with Hexabrix than Conray (p less than 0.01 and p less than 0.02 respectively). The incidence of nausea, vomiting, and hypersensitivity was similar. Angiographic quality was better with Conray than with Hexabrix (p less than 0.05). Average changes in heart rate and systolic pressure were similar, though there was greater variation in systolic pressure change after Conray (p less than 0.025). End diastolic pressure increased more after Conray than after Hexabrix (p less than 0.05). These slight advantages of Hexabrix over Conray may be valuable in patients requiring multiple angiograms or in those with impaired cardiac function, but do not justify its use for routine angiography.

Between January 1979 and December 1981, 142 patients undergoing surgery to the right coronary artery agreed to have repeat coronary arteriography one year later. Thirty patients underwent combined endarterectomy and bypass grafting to the right coronary artery. The patency of these grafts was compared with that of grafts in 69 patients undergoing direct grafting to the right coronary artery and in 43 with grafting to the posterior descending coronary artery. There were two hospital deaths and one late death. No patients developed new inferior Q waves on the electrocardiogram. Repeat coronary arteriography at one year showed that 21 (72%) of the 29 grafts were patent after combined endarterectomy and bypass grafting to the right coronary artery. Sixty three (94%) grafts to the right coronary artery and 40 (93%) grafts to the posterior descending coronary artery were patent at one year. Direct grafts to the right coronary artery or its posterior descending branch had a significantly higher patency rate at one year than grafts to the endarterectomised right coronary artery. Graft patency after the combined procedure correlated with the extent of atherosclerosis in the posterior descending coronary artery. It was not influenced by treatment with platelet antagonists. Endarterectomy of the right coronary artery was most successful when it allowed a single graft to perfuse both the large posterior descending and left ventricular branches.

Sixty three patients with chest pain typical of angina and who had normal coronary angiograms were investigated for left ventricular, oesophageal and psychiatric abnormalities. An additional 21 patients, age and sex matched, who had angina and significant coronary artery disease were also studied. Eighty six per cent of the 63 patients without evidence of coronary artery disease could be demonstrated to have a physical abnormality (left ventricular dysfunction in 35%, oesophageal disorder 51%). There was, however, a wide variation in the incidence of psychiatric morbidity between the diagnostic subgroups-18% in left ventricular dysfunction, 29% in those with coronary artery disease and 59% in patients with oesophageal disorders (P less than 0.01). Thus failure to identify left ventricular dysfunction and inclusion of such subjects in psychological assessments of 'angiogram-negative' chest pain might give misleading results. This study confirms that patients with angina and normal coronary angiography have a high incidence of oesophageal disorders. However psychiatric illness is also common in this group of subjects and management needs to take both these factors into account. [ABSTRACT FROM PUBLISHER]

This article reports that diabetes mellitus (DM), mainly type 2 diabetes, has affected approximately 100 million people worldwide, including 17 million in the U.S. and 1.15 million in Great Britain. A 30% increase in incidence is predicted by 2025, due to both the increased rate of obesity and the aging populations living in industrial countries. DM is a predictor of poor prognosis after acute myocardial infarction, congestive heart failure, and all modes of coronary revascularisation. Since the duration of DM is a powerful independent risk factor for coronary heart disease mortality, this conclusion needs further confirmation.

Background: Transforming growth factor-β1 (TGF-β1) has been implicated in the pathogenosis of coronary vasculopathy following cardiac transplantation. The TGFB1 gene contains polymorphisms at positions +915&ast; (Arg25Pro) and +869&ast; (Leu10Pro) which may influence TGF-β1 expression. We investigated the relationship between the development of coronary vasculopathy and the prevalence of these alleles in a cardiac transplant population. Methods: Vasculopathy was diagnosed at routine surveillance post-transplant coronary angiography. Using sequence-specific polymerase chain reaction we identified the TGFB1 +915&ast; and +869&ast; genotypes in 147 cardiac transplant recipients and 134 cardiac donors. Results: TGFB1 +915&ast;C allele carriers (low producers) made up 10.5% of the recipient population but were significantly less likely to develop coronary vasculopathy (P=0.03). Median time to diagnosis was 6.0 years (3.9–8.72) in +915&ast;C allele carriers compared to 2.75 years (2.10–4.22) in &ast;G/G homozygotes (p=0.002). Pre- and I year post-transplant clinical variables were equivalent between the two groups. Multivariate analysis identified the recipient +915&ast;G/G genotype (hazard ratio 2.96 (95% CI, 1.09–9.98); p=0.039), donor age (hazard ratio 1.05 (95% CI, 1.02–1.09); p=0.008) and number of acute rejection episodes of ISHLT grade 3 or greater in the first year (hazard ratio 1.12 (95% CI, 1.01–1.23); p=0.03) as significant predictors of vasculopathy. The recipient TGFB1 +869&ast;, and both alleles in the donor, had no influence on vasculopathy development. Conclusions: Recipient TGFBI +915&ast; genotype influences the development of cardiac transplant-related coronary vasculopathy. This gives an important insight to the pathophysiology of the disease. On the contrary, donor TGFB1 +915&ast; and TGFB1 +869&ast; polymorphisms do not appear to be important and cannot be used as genetic risk factors. [ABSTRACT FROM AUTHOR]