Intracoronary papaverine and complete atrioventricular block.
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Biomedical subjects
Publications and source records attributed to P M Schofield.
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The functional effects of coronary occlusive disease (COD) in cardiac transplant patients on small-resistance coronary vessels are unclear. We investigated the changes in coronary flow reserve (CFR) in response to the non-specific smooth muscle vasodilator papaverine. A 3F Doppler probe was inserted into the left anterior descending (LAD) coronary artery in 61 patients following orthotopic heart transplantation. Studies were performed in 57 males and 4 females with a mean age of 46 years (range 20-61 years). The median time from operation was 4 years (range 3 months to 10 years). Coronary blood velocity was measured at rest (RFV) and maximum hyperaemia (PFV) produced by intracoronary papaverine. Coronary flow reserve (CFR) was defined as the ratio of PFV to RFV. Minor lesions in epicardial vessels were found in 23 transplant patients. The mean percentage diameter of the most severe lesion in the coronary tree was 23% SD 3% including 12 lesions in the LAD coronary artery itself (mean 24% SD 4%). Patients with COD had an impaired CFR (2.6 SEM 0.2) compared with normals (3.9 SEM 0.2, P = 0.0003), adjusting for year after operation. Mean resting flow velocity was similar in both groups (minor COD, 6.8 cm/s SEM 1.2; normals, 7.1 cm/s SEM 0.6), but mean peak flow velocity response to papverine was reduced (16.5 cm/s SEM 2.5 versus 27.3 cm/s SEM 2.6; P = 0.007). In the presence of minor epicardial disease, coronary flow reserve in resistance vessels was reduced due to impairment of peak flow. This demonstrates that non-endothelial-dependent coronary resistance vessel vasodilatation is abnormal and may be caused by a defect in vascular smooth muscle function.
Angina and increasing exertional dyspnea developed in a 53-year-old man 9 years after cardiac transplantation. Left heart catheterization revealed severe proximal triple coronary artery disease, and he underwent surgical revascularization. Now 18 months after the operation he continues to be free of symptoms.
We describe right atrial thrombus complicated by tricuspid valve obstruction in a patient with constrictive pericarditis. This report highlights the role of surgical thrombectomy, and the investigation of constrictive pericarditis to exclude intra-cardiac thrombus.
The objective of this blinded, randomized, prospective study was to assess whether supplementation of normal diet with omega-3 polyunsaturated fatty acids can reduce angiographically defined restenosis following coronary angioplasty. The study included all patients undergoing coronary angioplasty in this institution between January 1988 and January 1989. One hundred and twenty patients enrolled, 60 in each treatment group. All were randomized to either supplementation of normal diet with 3 g of omega-3 polyunsaturated fatty acids per day started 1-2 days prior to angioplasty and continued for 6 months (treatment group), or to receive standard therapy only (control group). Quantitative angiographically defined restenosis was assessed at 6 months post angioplasty. Restenosis occurred in 27.8% (95% CI 18.0-37.7%) of lesions in the treatment group and in 28.3% (CI 16.9-39.7%) of lesions in the control group, but the difference was not statistically significant. The study showed that diet supplemented with 3 g of omega-3 polyunsaturated fatty acids started 1-2 days preceding angioplasty does not reduce angiographically defined restenosis rate.
OBJECTIVE: Coronary occlusive disease is the main cause of late mortality after cardiac transplantation. It has both similarities and differences compared with conventional atherosclerotic coronary disease. The pathophysiology of late graft failure from coronary occlusive disease is unclear at present. We reviewed the experience of this disorder in our cardiac transplant programme. DESIGN: A retrospective analysis of angiographic and pathological data. SETTING: A regional cardiothoracic centre and transplant unit. PATIENTS: Of a population of 383 orthotopic cardiac transplant recipients operated upon between January 1979 and June 1990, 447 coronary angiograms were available for review in 193 patients. Thirteen of a possible 18 results of post mortem examinations from patients dying from coronary occlusive disease were available. MAIN OUTCOME MEASURE: Coronary occlusive disease was defined as any evidence of disease on coronary angiography. Post mortem examinations were performed with standard techniques. RESULTS: The angiographic prevalence of coronary occlusive disease was 3% (1/32 patients) and 40% (19/47 patients) at one and five years respectively. Twenty six grafts failed due to coronary occlusive disease compared with 132 graft failures from all causes during this period. Acute thrombosis was present in a large vessel in seven of 13 fatal cases undergoing necropsy (54%). Noticeable large vessel involvement with disease in smaller distal vessels was present in four patients (31%). The remaining two patients (15%) had small vessel disease alone. Twelve of the 13 patients had significant cardiomegaly (cardiac weight > or = 400 g) with a mean weight of 510 (range 370-740) g. CONCLUSION: Coronary occlusive disease is the main late complication after cardiac transplantation. A combination of coronary thrombosis, ischaemia from stenoses of large and small coronary vessels, and cardiomegaly contribute to the graft failure of these patients.
OBJECTIVE: Coronary occlusive disease is the major long-term complication after cardiac transplantation. The relation between minor angiographic abnormalities and myocardial perfusion has not been previously assessed in a large number of cardiac transplant patients. DESIGN: Prospective study. Coronary flow reserve was measured with an intracoronary Doppler flow probe in the proximal left anterior descending coronary artery in each patient. A dose of intracoronary papaverine producing maximal vasodilation was then administered. SETTING: A regional cardiothoracic centre and a supraregional transplant unit. PATIENTS: Seven patients with chest pain but normal coronary anatomy (controls), and 61 cardiac transplant patients between three months and 10 years after operation (median 4.5 years). Twenty one cardiac transplant patients had angiographic evidence of minor coronary occlusive disease (mean (SD) percentage stenosis diameter 23% (6%)) in a primary or secondary coronary vessel (group 1), with 12 of these in the left anterior descending coronary artery (stenosis diameter (mean (SD) 24% (8%)). The remaining 40 transplant patients had normal coronary angiograms (group 2). MAIN OUTCOME MEASURE: Coronary flow reserve was defined as the ratio of the peak flow velocity after papaverine to the resting flow velocity. RESULTS: Group 1 patients had a noticeably impaired coronary flow reserve (2.6 (1.1)) compared with control patients (3.9 (0.4), p = 0.05) and, after adjusting for year after operation, compared with group 2 patients (3.8 (1.0), p < 0.001). No other variables were associated with a reduction in coronary flow reserve. Mean resting flow velocity was similar in all three groups (controls, 7.4 (4.6) cm/s; group 1, 7.5 (5.9) cm/s; and group 2, 7.3 (3.9) cm/s). Mean peak flow velocity response to papaverine was reduced in group 1 patients (18.1 (13.5) cm/s) relative to group 2 patients (27.5 (15.4) cm/s, p = 0.05) but not controls (28.4 (15.1) cm/s, p = 0.1). CONCLUSIONS: Coronary flow reserve and the peak flow response to the coronary vascular smooth muscle relaxant papaverine are impaired in cardiac transplant patients with minor coronary occlusive disease. This disturbance of cardiac microvascular function may contribute to the late morbidity and mortality seen in cardiac transplant patients with coronary occlusive disease.
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We evaluated the role of percutaneous transluminal coronary angioplasty (PTCA) in a series of orthotopic cardiac transplant recipients with severe epicardial coronary occlusive disease. Ten orthotopic cardiac transplant patients treated by PTCA up to March 1990 were reviewed. All had significant epicardial coronary artery lesions (greater than 70% stenosis compared with the adjacent healthy artery) and exercise electrocardiogram or isotope perfusion evidence of myocardial ischaemia in the relevant region. Primary angiographic PTCA success was achieved in 12 of the 16 lesions attempted (75%). Mean stenosis improvement was from 80% of adjacent healthy artery (range 70-90%) to 12% (range 0-20%). Median angiographic follow-up of 9 months (2-25 months) is available for all patients. The mean recurrence rate is 33% (4 of 12 successfully treated lesions) defined as greater than 50% reduction in the original gain at the PTCA. We have shown that PTCA is technically possible in a series of cardiac transplant recipients. The primary success and recurrence rates are comparable to the use of PTCA in conventional atherosclerotic coronary disease.
This study demonstrates the importance of analyzing survival by cause of death in order to achieve a better understanding of the prognostic indicators involved. It further emphasizes the need for analysis of risk factors in both univariate and multivariate models, and the danger of making judgements based on premature analysis of data on follow-up after heart transplantation. Survival following transplantation is characterized by the major hazards of early death due to infection and rejection and late graft loss due to coronary occlusive disease (COD). This study summarizes the first-graft survival experience for 323 transplant patients at Papworth Hospital, and assesses a number of potential risk factors for (1) early mortality, (2) late mortality from COD, and (3) development of COD. The potential risk factors considered for all hazards are donor and recipient age, sex, blood group, and matching of these factors; donor cause of death and recipient immunosuppression; inotropic support; waiting time; preoperative diagnosis and previous cardiac surgery; ischemic time; and extubation time. In addition, for development of, and graft loss from, COD, perioperative rejection and cytomegalovirus infection; hypertension at discharge; and cholesterol, triglycerides, and lipids at two years were assessed as risk factors. Advances in immunosuppression were observed to have increased overall survival rates and decreased mortality from infection, rejection, and COD, as well as decreasing morbidity from COD. Fatal rejection was found to be more likely in female recipients, recipients over 40 years, recipients of grafts from donors over 30 years old, patients who were transplanted for valvular heart disease, and patients who waited less than three months for their transplant. Male recipients of female donor organs were more likely to lose their grafts as a result of COD. Patients older than 50 and hearts from donors older than 40 conferred a high risk of development of and loss from COD. Patients transplanted for ischemic heart disease were more likely to develop COD. High cholesterol, low HDL, high LDL, and high triglycerides at two years after transplant showed some evidence of high risk for the subsequent development of COD, although these relationships are not statistically significant at this stage. Contrary to other recent studies, cytomegalovirus infection was not found to be a risk factor for the development of COD.
1. Fifty patients with symptoms due to chronic heart failure despite diuretic therapy were randomised to receive additional treatment with either hydralazine or captopril. The dose was titrated; 24 received hydralazine and 26 captopril up to a maximum daily dosage of 225 mg and 75 mg respectively. Forty-three patients had coronary heart disease and seven dilated cardiomyopathy. 2. Dyspnoea and tiredness were assessed using a visual analogue scale (0-100) before and during 12 weeks' treatment. Captopril produced a significantly greater reduction in breathlessness (F = 31.6, P less than 0.001) and tiredness (F = 65.8, P less than 0.001) compared with hydralazine. 3. There was an increase in treadmill exercise time during treatment with both hydralazine (from 5.5 (3.47-7.53) min to 6.9 (4.87-8.93) min), and captopril (from 5.0 (3.05-6.95) min to 7.8 (5.85-9.75) min), but the degree of improvement was significantly greater in the patients treated with captopril (F = 7.4, P less than 0.001). 4. There was no significant change in right ventricular ejection fraction (from 27.9 (19.3-36.5)% to 28.7 (20.1-37.3)%) or left ventricular ejection fraction (from 22.2 (14.2-30.2)% to 23.9 (15.9-31.9)%) during treatment with hydralazine. However, both right and left ventricular ejection fraction increased significantly during treatment with captopril (from 27.1 (18.9-35.3)% to 32.0 (23.8-40.2)%, P less than 0.05; and from 25.0 (17.2-32.8)% to 29.6 (21.8-37.4)%, P less than 0.05 respectively). 5. These results suggest that in patients with symptoms due to chronic heart failure despite diuretic therapy, treatment with captopril produces a greater symptomatic and haemodynamic improvement than treatment with hydralazine.
Reliable diagnosis of cardiac allograft rejection is at present only possible using endomyocardial biopsy. We have serially measured epicardial evoked T wave amplitude during ventricular pacing with an externalized QT driven rate responsive pacemaker telemetered to a TP2 analyzer in 13 patients (12 males) followed for 19 (14-26) days after transplantation. A total of 228 records were analyzed. Rejection was defined on endomyocardial biopsy. On 17 of the 31 occasions on which biopsy was performed during the study, specimens showed significant (moderate) rejection. In 11 patients the initial biopsy proven rejection episode was associated with a significant fall in the evoked T wave amplitude from 1.3 (0.7-2.3) mV to 0.6 (0.5-1.8) mV (P less than 0.005), which began 2 (1-4) days earlier. One patient with uncontrolled diabetes mellitus had no change in evoked T wave amplitude during rejection. The evoked T wave amplitude did not fall in the absence of histologic rejection. These results suggest a noninvasive method for detecting cardiac rejection, which appears both sensitive (92%) and specific (100%) in the first rejection episodes.
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A 53 year old woman with symptomatic pacemaker associated superior vena cava syndrome was treated successfully with balloon angioplasty. She was well six months after the procedure.
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