Coronary arteriopathy after heart transplantation.

PURPOSE: To describe changes in the coronary artery following heart transplantation (HTx) in patients who survived for 1 year or more. MATERIAL AND METHODS: Yearly ventriculography and coronary angiography were performed in 171 out of 172 patients aged over 12 years who survived HTx in Norway for 1 year or more after the first operation in 1983. Mean follow-up was 5.2 years +/- 2.8, range 1-12. RESULTS: Altogether 31 patients died in the follow-up period, 8 (26%) of them from coronary artery disease (CAD). Angiographic changes included coronary artery stenoses, diffuse changes with ectatic and narrowed segments of the major coronary vessels, peripheral changes with occlusions and tapering of the small vessels, and reduction in the left ventricular ejection fraction (EF). Significant stenosis developed in 43 patients and 19 of these developed an occlusion of one of the major coronary artery branches. The coronary arteries were without significant stenosis in 97% of the surviving 141 patients at 1 year after HTx and in 82% at 5 years. Completely normal findings were seen in 81% after 1 year and in 44% after 5 years. Progression to significant stenosis and occlusion was rapid once changes first appeared. CONCLUSION: CAD contributed to a significant number of deaths. The stenoses could develop at any time after transplantation and usually progressed rapidly once the first changes appeared.

[Mortality, recurrent angina pectoris and late myocardial infarction in patients surgically treated for coronary heart disease]. / Dødelighet, tilbakefall av angina pectoris og seninfarkt hos pasienter operert for koronar hjertesykdom.

This cohort study includes 1,025 patients operated between 1982 and 1986 at Rikshospitalet, the National Hospital of Norway, 912 men and 113 women. The closing date was 1 January 1993. A total of 31 patients (3%) died within 30 days of operation. Independent risk factors were atrial fibrillation, previous heart surgery, mitral insufficiency, left main stem stenosis, unstable angina pectoris and elevated end-diastolic pressure. Among the 164 patients (16%) who died more than 30 days after operation, the independent risk factors of total mortality were atrial fibrillation, concomitant resection of left ventricular aneurysm, left main stem stenosis, NYHA functional class IV on admission, elevated end-diastolic pressure and prolonged cross-clamping time. Recurrent angina pectoris was experienced by 146 patients (14.2%) while 102 patients had non-fatal myocardial infarction. The cumulative incidence of these conditions was initially low, but began to increase four year after operation. The independent risk factor for these two end-points was hypertension. The study suggests that stratification of independent risk factors facilitates comparison of mortality in different centres and permits improved quality control.

[Mortality and morbidity after coronary bypass surgery in high-risk patients]. / Dødelighet og sykelighet etter koronar bypasskirurgi hos høyrisikopasienter.

A total of 113 women and 912 men were submitted to coronary artery bypass surgery at Surgical Department A, Rikshospitalet between August 1982 and December 1986 and followed till January 1993. We found no difference in early mortality, recurrent angina pectoris or non-fatal myocardial infarction in diabetic patients compared to nondiabetic patients. However, total mortality was 1.87 times higher in the diabetic group. For patients with ejection fraction < or = 40%, early mortality was 10.2 times higher than for the reference group. For total mortality we found a practically linear relationship between increased mortality and falling ejection fraction values. We found no relationship between ejection fraction and recurrent angina and non-fatal myocardial infarction, neither did we find any difference in mortality and morbidity between women and men. Although a somewhat higher mortality and morbidity rate must be expected for high-risk patients, they seem to profit to the same extent from the favourable effects of coronary bypass surgery as other patients.

Coronary artery bypass surgery in women and in men; early and long-term results. A study of the Norwegian population adjusted by age and sex.

OBJECTIVE: We wished to analyse early mortality, postoperative low-output syndrome needing intra-aortic balloon pumping support (IABP), total mortality, recurrent angina pectoris and total non-fatal myocardial infarction in women compared with men. Also, the standard mortality ratio (SMR) was estimated to compare the mortality data to the general Norwegian population of comparable sex and age. METHODS: A total of 1025 patients; 113 women and 912 men, were submitted to coronary artery bypass surgery at Rikshospitalet, Oslo between August 1982 and December 1986. The patients were followed up until the 1st of January 1993, representing a mean follow-up time of 7.4 years. An exposed/non-exposed cohort study design was used. A power study was carried out. The standardized mortality ratios for women and men were calculated after adjusting for age and sex. RESULTS: Crude odds ratio (ORC) of early mortality was 2.0 with a 95% confidence limit (CL95%) of 0.7-5.4. Odds ratio of low output syndrome needing intra-aortic balloon support was 1.7 (CL95% = 0.8-4.2). Statistical significance was not achieved for these end-points. Women did not run an increased hazard of total mortality (ORC = 0.9; CL95% = 0.5-1.5), recurrent angina pectoris (ORC = 1.4; CL95% = 0.8-2.4) or of total non-fatal myocardial infarction (ORC = 0.8; CL95% = 0.4-1.6) when compared with men. Adjusting for confounders did not significantly alter the results. When matched on sex and age and compared to the normal Norwegian population, we found an increased SMR in both men (2.5; CL95% = 2.2-2.9) and women (4.1; CL95% = 2.2-4.9). CONCLUSION: The risk of early mortality and low-output syndrome needing intra-aortic balloon support tended to be higher in women compared with men. Women did not run an increased risk of total mortality, recurrent angina or of total non-fatal myocardial infarction. The standard mortality ratio was increased in both men and women, but in particular higher in women, suggesting a more aggressive course of coronary artery disease in operated women than in operated men. However, this difference did not show in the long term follow-up, due to the beneficial effect of coronary artery bypass surgery in both men and women.

Percutaneous transluminal angioplasty and retransplantation due to transplant coronary artery disease.

Allograft vascular disease is a significant cause of death of cardiac transplant recipients after the first year of transplantation. With few exceptions, angina pectoris does not develop and objective examinations, including coronary angiography, are necessary to diagnose coronary arteriopathy. Between 1983 and 1994, 214 heart transplantations in 211 patients were performed in our unit. All survivors had coronary angiography performed yearly. Thirty patients had significant localized arterial stenoses. Twelve patients with critical stenosis were accepted for percutaneous transluminal coronary angioplasty. Five patients underwent retransplantation due to progressive graft vascular disease with development of congestive heart failure. Conventional revascularization with transluminal coronary angioplasty can safely be performed with primary good results. In selected patients, retransplantation is an option if patients otherwise fulfil standard criteria for cardiac transplantation.

Mortality and morbidity after coronary artery bypass surgery related to pre-operative left ventricular ejection fraction: a follow-up study.

OBJECTIVE: To study the pre-operative level of left ventricular ejection fraction that may be indicative of an increased risk of early and late mortality and of recurrent angina pectoris and late non-fatal myocardial infarction. MATERIAL AND METHODS: A total of 934 patients with known left ventricular ejection fraction, 80 women and 854 men, were submitted to coronary artery bypass grafting at the Cardiovascular Unit of Rikshospitalet, Oslo, between August 1982 and December 1986. The closing date was the 1st of January 1993, with a mean follow-up of time of 7.4 years. The patients were divided in to four subgroups according to their level of left ventricular ejection fraction: < or = 40%, 41-60%, 61-80% and > 80%. The left ventricular ejection fraction varied from 13-98%. A chi-square test of linear trend was used to calculate the relative risk between the different subgroups. Cumulative survival was determined using survival curves. RESULTS: Early mortality. Twenty-five patients (2.7%) died within 30 days of operation. Patients with left ventricular ejection fraction < or = 40% had a relative risk of 10.2 (1.9-17.2), for left ventricular ejection fraction 41-60% the relative risk was 0.9 (0.1-8.9) and for left ventricular ejection fraction 61-80% the relative risk was 2.8 (0.6-17.2). Left ventricular ejection fraction > 80% was defined as relative risk = 1. Late mortality. Altogether, 174 patients died in the late phase (18.6%). For patients with left ventricular ejection fraction < or = 40% the relative risk was 3.6 (2.8-10.9), for left ventricular ejection fraction 41-60% the relative risk was 1.8 (1.1-3.6), and for left ventricular ejection fraction 61-80% the relative risk was 1.5 (0.9-2.8). Recurrent angina pectoris. A total of 138 patients developed recurrent angina pectoris during the follow-up period, giving an incidence of 14.8%. Here, for left ventricular ejection fraction < or = 40% the relative risk was 0.5 (0.2-1.3), for left ventricular ejection fraction 41-60% the relative risk was 1.0 (0.5-1.8) and for left ventricular ejection fraction 61-80% the relative risk was 1.2 (0.7-2.0). Late non-fatal myocardial infarction. Altogether, 90 patients (9.6%) experienced non-fatal myocardial infarction in the late phase. For left ventricular ejection fraction < or = 40% the relative risk was 0.6 (1.2-1.8), for left ventricular ejection fraction 41-60% the relative risk was 1.0 (0.5-2.0) and for left ventricular ejection fraction 61-80% the relative risk was 0.7 (0.41-1.3). Cumulative survival. When pooled together, the cumulative survival for patients with left ventricular ejection fraction > 40% was 95.9, 91.9 and 79% after 1, 5 and 10 years, respectively. For the patients with left ventricular ejection fraction < or = 40% cumulative survival was 87.5, 73.1 and 55.2%, respectively. CONCLUSION: When the left ventricular ejection fraction was 40% or lower, there was a substantial increase in the risk of early mortality in patients submitted to coronary artery bypass grafting. As for the risk of late mortality, there was a practically linear increase in risk with falling values of left ventricular ejection fraction. We found no difference in risk of developing recurrent angina pectoris or of late non-fatal myocardial infarction related to values of left ventricular ejection fraction.

Diabetes mellitus and morbidity and mortality risks after coronary artery bypass surgery.

Of 1025 patients (912 men, 113 women) who underwent coronary artery bypass grafting and were followed up for a mean of 7.4 years, 45 (4.4%) had diabetes mellitus. Norwegian population is 1.8-2%). Early mortality was not significantly greater among diabetics than in non-diabetics (2.2 vs. 3.1%, odds ratio--OR-0.44, confidence interval--CI- 0.05-3.56). Diabetic patients had no increased risk of perioperative myocardial infarction (OR = 0.87, CI 0.36-2.10) or of low-output syndrome necessitating intraortic balloon pumping (OR = 0.42, CI 0.55-3.05), and no excess incidence of late non-fatal myocardial infarction (relative risk = 0.69, CI 0.10-1.28) or late chronic heart failure (OR = 2.50, CI 0.5-11.0). Long-term mortality was increased in the diabetic patients (relative risk 1.87, CI 1.60-2.14). Thus diabetes did not entail heightened risk of early mortality, perioperative myocardial infarction or low-output syndrome. Nor was there excess risk of recurrent angina pectoris, late non-fatal myocardial infarction or chronic heart failure among the diabetic patients, but the late mortality risk was increased.

Risk factors of recurrent angina pectoris and of non-fatal myocardial infarction after coronary artery bypass surgery.

The long-term results of 1025 patients, 912 men and 113 women, undergoing coronary artery bypass grafting (CABG) at the Cardiovascular Unit of Rikshospitalet, Oslo, between 1982 and 1986, were analyzed on factors associated with the return of angina pectoris and of non-fatal post CABG myocardial infarction. The closing date was 1st January 1993, with a mean follow-up time of 7.4 years. Recurrent angina pectoris was experienced by 118 (11.6%) patients and 102 (10%) patients experienced non-fatal post CABG myocardial infarction during the observation period. Altogether 30 possible risk factors were analyzed. The cumulative incidence of recurrent angina was initially low after operation, followed by a rise after 4 years. One, 5 and 10 years after the operation, survival free from angina rates were 97.8%, 91.8% and 80.6%, respectively. The cumulative incidence of post CABG myocardial infarction was also low initially, followed by a rise after 4 years. The survival free of non-fatal post CABG myocardial infarction rate was 98.9%, 96% and 83.5%, at 1, 5 and 10 years after surgery, respectively. The incremental risk factor of recurrent angina pectoris was hypertension. The independent risk factors of non-fatal post CABG myocardial infarction were hypertension and preoperative stenosis of the left-sided, versus right-sided, coronary arteries. The study emphasizes the favorable effect of coronary bypass surgery on the functional outcome in patients with symptomatic coronary artery disease.

Risk factors for early and late mortality in surgical treatment of coronary artery disease.

A total of 1025 patients who had coronary bypass surgery at the Surgical Department A, Rikshospitalet, Oslo, between 1982 and 1986, were analysed for factors associated with early mortality and long-term survival. The cumulative follow-up time accounted for 6553 patient-years; the median follow-up was 6.45 years and ranged from the day of admission to 10 years. In total, 31 patients (3%) died within 30 days of surgery. Some 30 possible risk factors were analysed. Univariate analysis followed by a multivariate analysis defined six independent risk factors for early mortality. These were lack of sinus rhythm, previous heart surgery, mitral regurgitation, left main stem stenosis, unstable angina, and an elevated left ventricular end-diastolic pressure. Estimation of attributable risk showed that these factors could identify all patients who died early. Independent risk factors for late death were: lack of sinus rhythm, resection of a left ventricular aneurysm, left main stem stenosis, New York Heart Association (NYHA) class IV on admission, an elevated end-diastolic pressure, and prolonged cross-clamping time. The attributable risk analysis showed that independent risk factors for total mortality explained only about half of the patients who died. This appeared to be because of the competing effect of non-cardiac mortality. Results of the study show that risk factors for early mortality are good indicators for the outcome of coronary artery bypass surgery, identifying all deaths, whereas long-term mortality cannot be predicted. Stratification of independent risk factors allows a better comparison of mortality in different centres, and also better quality control of bypass surgery.

Coronary angioplasty using a low osmolar nonionic contrast medium. A retrospective angiographic and clinical evaluation.

This study was performed to investigate the occurrence of acute angiographic and clinical complications following PTCA using a low osmolar nonionic contrast medium. Five hundred consecutive PTCA procedures were analyzed retrospectively. The incidence of acute in laboratory complications during PTCA as well as complications occurring during the hospital stay 24 to 48 hours after the procedure were recorded. Occlusion of the dilated artery or a side branch was observed in 19 (3.8%) of the procedures, major dissection in 34 (6.8%), and thrombus in 14 (2.8%). One patient died, 6 (1.2%) required emergency coronary artery bypass grafting (CABG), 4 (0.8%) required an emergency PTCA, and 7 (1.4%) suffered myocardial infarction (MI). Our results show that angiographic findings of thrombus, major dissection and occlusion were serious conditions that related to the clinical complications MI, emergency CABG and re-PTCA. Patients with unstable angina were risk patients for both angiographic and clinical complications. Low rates of intraarterial thrombus formation and coronary artery occlusion indicate good angiographic technique and anticoagulant and antiplatelet medication.

Cerebral thromboembolic complications associated with the use of a nonionic contrast medium in coronary angiography.

Cerebrovascular complications were registered in 11 patients (0.21%) of 5,339, consecutively submitted to coronary angiography with the nonionic contrast medium iohexol (Omnipaque). Six of the patients had diseases predisposing them to thromboembolic complications, 3 of whom earlier had symptoms of cerebral stroke. Excluding these 6, the incidence of cerebral thromboembolic events was 0.10% in patients with no predisposing diseases. Precise catheterization technique and some anticoagulation and antiplatelet activity therapy are definite precautions against these complications, while the role of the contrast medium is still debated.

Iodixanol in cardioangiography in patients with coronary artery disease. Tolerability, cardiac and renal effects.

Iodixanol is a new nonionic, dimeric contrast medium. With the addition of 18 mmol/l Na+ and 0.3 mmol/l Ca++ to iodixanol 320 mg I/ml a plasma-isotonic solution was obtained. The purpose was to evaluate the suitability of iodixanol for use in cardioangiography by determining the diagnostic efficacy, patient tolerability, and cardiac and renal side-effects. Initially, 14 patients with coronary artery disease were examined using iodixanol. A double-blind, randomized study was then performed in 72 patients, comparing iodixanol and iohexol. Serum and urine were sampled before the examination, and one and 2 days after. The diagnostic information was good and the number of adverse events low with iodixanol. The patients reported significantly less of a sensation of warmth following injection of iodixanol than iohexol. Our results also indicate that iodixanol 320 mg I/ml influences renal function to a lesser degree than does iohexol 350 mg I/ml. We therefore conclude that isotonic iodixanol is a safe contrast medium for use in cardioangiography.

Lipoprotein-related coronary risk factors in patients with angiographically defined coronary artery disease: relation to number of stenosed arteries.

To determine whether an index estimating antagonism between low density lipoprotein (LDL) and high density lipoprotein (HDL) would improve separation between groups with and without coronary artherosclerosis, patients undergoing coronary catheterization (35 women and 99 men) were analysed for total cholesterol (TC), HDL cholesterol (HDLc), apolipoprotein A (apo A) and apolipoprotein B (apo B). The subjects were categorized as groups 0, 1, 2 or 3 according to the number of stenosed arteries (greater than 75% areal stenosis). Thirty of the patients showed no significant coronary atherosclerosis (group 0). Serum apo B and TC concentrations were directly related to the number of stenosed vessels, whereas the concentrations of apo A and HDLc were negatively correlated with the number of stenosed arteries. An 'atherogenic Index' (ATH index) calculated as the product of serum concentrations of apo B, and TC minus HDLc divided by the product of apo A and HDLc, proved more satisfactory than individual lipoprotein components for discrimination between subjects with and without stenosis. Accordingly, identification of coronary groups may be improved by using the ATH index.

Serum HDL2 distribution in patients with coronary heart disease and controls as estimated by a precipitation reaction between HDL2 and an extract of Staphylococcus capitis.

Serum HDL2 concentration has been shown to be lowered in patients with coronary heart disease (CHD). Since we previously reported that serum HDL2 can be estimated by single radial diffusion in agar containing an extract of Staphylococcus capitis, it seemed of interest to study whether serum HDL2 as estimated by this method is different in CHD patients and controls. It was shown that relative activity of HDL2, assessed by the method, was appreciably lower in 40 men with angiographically proven coronary artery disease (CAD) than in a control group of 39 men of the same age. Also apolipoprotein A (apo A) concentration was lower in the CAD group, but group difference in HDL2 activity was greater than separation based upon apoA. It is suggested that precipitation with an extract of Staphylococcus capitis might be a useful approach to estimate serum HDL2 levels.

Percutaneous transluminal coronary angioplasty. Six years experience.

In a six-year period (1982-1987), 248 patients were treated with 297 procedures (percutaneous transluminal coronary angioplasty, PTCA) on 282 vessels. Two hundred and fifty-nine (87.2%) of the procedures in 210 (76.7%) of the patients appeared successful angiographically. Thirty-eight procedures were unsuccessful due to failure to pass the stenosis in 18 patients, dissection or occlusion of the treated vessel in 11, and significant residual stenosis in 9 patients. Emergency operations were performed after 11 (3.7%) of the procedures. Two patients died postoperatively. Myocardial infarction was seen in 13 patients, of whom 4 developed pathologic Q-waves in their ECG. Restenosis occurred in 60 (28.6%) of the patients. In the last year of the study, the patients selected for PTCA were in a poorer state angiographically, but the results of PTCA were better, without any increase of the complication rate. Our results, which are in accordance with others, support the concept that PTCA is a relatively safe procedure with a primary success rate of almost 90 percent. However, approximately one third of the patients developed restenosis, which in most cases occurred within 3 months.

Safety of the nonionic contrast medium omnipaque in coronary angiography.

The low osmolar nonionic contrast medium Omnipaque was used in 5,339 consecutive coronary angiographies and serious complications were registered. Myocardial infarction occurred in 4 patients, of whom 2 died, and ventricular fibrillation in 1. Cerebral embolism occurred in 11 patients, all of whom survived. The results are compared with those of previous series of coronary angiography with high osmolar ionic media. It is concluded that use of the nonionic medium Omnipaque resulted in a significant reduction of the frequency of serious complications.

Quantification of mitral regurgitation by Doppler echocardiography.

The present study was undertaken to evaluate a new non-invasive approach to the quantification of mitral regurgitation. Doppler echocardiography and left ventriculography were performed in 20 patients without valvular heart disease (group A), and in 30 patients with pure mitral regurgitation (group B). Volumetric flows through the aortic and mitral valve orifices were determined by Doppler technique. The aortic flow (AF) was calculated as the product of the aortic orifice area by the systolic velocity integral. The mitral flow (MF) was computed as the product of the corrected mitral orifice area by the diastolic velocity integral. The mitral regurgitant fraction (RF) was calculated as: RF = 1 - AF/MF. In group A, there was a close agreement between aortic and mitral flows (r = 0.94, P less than 0.001), and there was no significant difference between the two measurements. In group B, the mitral flow was significantly higher than the aortic flow. The regurgitant fraction assessed by Doppler echocardiography correlated well with the grades of severity of regurgitation obtained at left ventriculography. We conclude that combined measurement of both aortic and mitral flows by Doppler echocardiography provides a new and promising approach to the noninvasive quantification of mitral regurgitation.

Prognostic factors for survival in surgically treated aortic regurgitation.

Aortic valve replacement was performed for 'pure' aortic regurgitation on 118 patients in a 5 1/2-year period ending in January 1983. In an analysis of prognostic factors, 12 variables were considered. The long-term survival rate was significantly greater in men than in women. Other significant factors were the relative heart volume, left ventricular systolic pressure and size of the implanted valve. A multivariate analysis with the Cox regression model, using the pool of variables simultaneously, showed primary predictive factors independently affecting survival to be left ventricular systolic pressure and size of the implanted valve. Based on this model, a patient-specific survival forecast was constructed.

Measurement of mitral regurgitation by Doppler echocardiography.

In an attempt to develop a new approach to the non-invasive measurement of mitral regurgitation, Doppler echocardiography and left ventriculography were performed in 20 patients without valvar heart disease (group A) and in 30 patients with pure mitral regurgitation (group B). Volumetric flows through the aortic and the mitral orifices were determined by Doppler echocardiography. Aortic flow (AF) was calculated as the product of the aortic orifice area and the systolic velocity integral. The mitral flow (MF) was calculated as the product of the corrected mitral orifice area and the diastolic velocity integral. The mitral regurgitant fraction (RF) was calculated as RF = 1 - AF/MF. In group A aortic and mitral flow were very similar and the difference between the two did not differ significantly from zero. In group B the mitral flow was significantly larger than the aortic flow. There was a good correlation (r = 0.82) between the regurgitant fraction determined by Doppler echocardiography and the regurgitant grades determined by left ventriculography. The regurgitant fraction increased significantly with each grade of severity. These results show that Doppler echocardiography can be used to give a reliable measure of both aortic and mitral flow. This technique is a new and promising approach to the non-invasive measurement of mitral regurgitation.