[DANAMI. A Danish study of invasive versus conservative treatment of patients with post-infarction ischemia who had received thrombolytic therapy]. / DANAMI. En dansk undersøgelse af invasiv versus medicinsk behandling af trombolysebehandlede patienter med postinfarkt iskaemi.

INTRODUCTION: To compare an invasive strategy employing percutaneous transluminal coronary angioplasty (PTCA) or coronary artery by-pass grafting (CABG) with a medical strategy in patients who had received thrombolytic treatment for first acute myocardial infarction (AMI), and with signs of inducible ischaemia. METHODS: In a prospective study 1008 patients were randomized, 503 to invasive treatment, of whom 266 (52.9%) had PTCA, and 147 (29.2%) CABG, 505 to conservative treatment, of whom eight (1.6%) were revascularized within two months. RESULTS: After a median follow-up of 2.4 years the mortality in the invasive group was 3.6% vs. 4.4% (p = 0.45) in the conservative group, re-infarction incidence was 5.6% vs. 10.5% (p = 0.0038) and percentage of admissions with unstable angina was 17.9% vs. 29.5% (p < 0.00001). DISCUSSION: We conclude that post-infarct patients with inducible ischaemia should be referred to coronary angiography and revascularised accordingly.

Health related quality of life after conservative or invasive treatment of inducible postinfarction ischaemia. DANAMI study group.

OBJECTIVE: To assess health related quality of life in patients with inducible postinfarction ischaemia. DESIGN: A questionnaire based follow up study on patients randomised to conservative or invasive treatment because of postinfarction ischaemia. SETTING: Seven county hospitals in eastern Denmark and the Heart Centre, National University Hospital, Copenhagen, Denmark. PATIENTS: 113 patients with inducible postinfarction ischaemia: 51 were randomised to conservative treatment and 62 to invasive treatment. Average follow up time was three years (19-57 months). MAIN OUTCOME MEASURES: SF-36, Rose angina and dyspnoea questionnaire, drug use, lifestyle, and cognitive function. RESULTS: Invasively treated patients scored better on the SF-36 scales of physical functioning (p = 0.03) and on role-physical (p = 0.04) and physical component scales (p = 0.05) and took significantly less anti-ischaemic drug treatment. Angina occurred in 18% of the invasively treated patients and 31% of the conservatively treated patients (p = 0.09). However, more invasively treated patients suffered from concentration difficulties (18% v 4%; p = 0.04). CONCLUSIONS: Patients who were treated invasively had better health related quality of life scores in the physical variables compared with conservatively treated patients. However, a larger proportion of invasively treated patients had concentration difficulties.

Gastric intrinsic factor production and vitamin B12 absorption after oesophageal resection using stomach as substitute.

OBJECTIVE: To investigate whether the use of the stomach as a substitute after oesophageal resections causes disturbances in vitamin B12 absorption due to deficient intrinsic factor (IF) production. MATERIAL AND METHODS: Eleven patients operated upon with oesophageal resection a.m. Ivor Lewis, for malignant (10) or benign (1) conditions of the oesophagus were examined with a postoperative dual isotope technique 11-41 months (mean 25 months) after operation. RESULTS: In two patients the test showed abnormally low absorption of vitamin B12. One of these probably due to incomplete urine collection during the test period. However, no patient showed deficient intrinsic factor production with absorption ratios between vitamin B12 +/- IF of 0.87-1.14 (reference interval: 0.70-1.20). CONCLUSION: Deficiency of intrinsic factor is neither an obligatory nor a common occurrence after oesophageal resection with gastric substitute. However, vitamin B12 absorption may be low due to other factors, and should be looked for in all patients surviving more than a couple of months postoperatively.

CABG shortly after AMI treated with thrombolysis: an analysis of the surgical group and a comparison with PTCA in the DANAMI study. Danish multicenter randomized study of invasive versus conservative treatment in patients with inducible ischemia after thrombolysis in acute myocardial infarction.

OBJECTIVE: To present surgical results of the DANAMI study comparing conservative and invasive treatment of postinfarction myocardial ischaemia and to compare these with percutaneous transluminal angioplasty (PTCA) which was the alternative invasive treatment in that study. METHODS: A group of 413 patients with verified acute myocardial infarction treated with thrombolysis within 12 h of the onset of symptoms, who demonstrated postinfarction myocardial ischaemia were treated with coronary artery bypass grafting (CABG) or PTCA. Patients with left main lesions, three-vessel disease, two-vessel disease with more than three stenoses and patients with occlusions of a non-infarct related vessel had primary CABG. Patients with 1- and 2-vessel disease with not more than a total of three stenoses had PTCA. In case of failed PTCA patients had secondary CABG. The median distance from AMI to CABG was 45 days. PTCA was performed at a mean of 39 days after the infarction. RESULTS: A total of 147 patients had CABG and 266 had PTCA. The operative mortality for CABG was 1.4%. No PTCA patients died in relation to the procedure, 0.8% developed acute myocardial infarction as a consequence of the procedure, 1.5% had acute CABG and 3.5% elective CABG due to failed PTCA. In spite of more severe coronary artery disease among the CABG patients there was no difference in survival at 2.4 years. The CABG group had significantly fewer episodes of unstable angina, 10.2% versus 25.6% (P = 0.0002). No CABG patients had re-do revascularisation at 2.4 years follow-up versus 15.4% of the PTCA patients. At 3 years 80% of the CABG patients were free of angina compared to the 61% of the PTCA group (P < 0.0001). CONCLUSION: Low morbidity and mortality justifies the deferred elective revascularisation in patients with postinfarction myocardial ischaemia even in patients with silent ischaemia. There is no difference in survival at 2.4 years between CABG and PTCA but CABG offers more lasting results concerning incidence of stable and unstable angina than PTCA, which, however, is a valuable alternative in patients with less severe coronary artery disease.

Danish multicenter randomized study of invasive versus conservative treatment in patients with inducible ischemia after thrombolysis in acute myocardial infarction (DANAMI). DANish trial in Acute Myocardial Infarction.

BACKGROUND: The aim of the DANish trial in Acute Myocardial Infarction (DANAMI) study was to compare an invasive strategy of percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG) with a conservative strategy in patients with inducible myocardial ischemia who received thrombolytic treatment for a first acute myocardial infarction (AMI). METHODS AND RESULTS: Of the 503 patients randomized to an invasive strategy, PTCA was performed in 266 (52.9%) and CABG in 147 (29.2%) from 2 to 10 weeks after the AMI. Of the 505 patients in the conservative treatment group, only 8 (1.6%) had been revascularized 2 months after the AMI. The patients were followed up from 1 to 4.5 years. The primary end points were mortality, reinfarction, and admission with unstable angina. At 2.4 years' follow-up (median), mortality was 3.6% in the invasive treatment group and 4.4% in the conservative treatment group (not significant). Invasive treatment was associated with a lower incidence of AMI (5.6% versus 10.5%; P=.0038) and a lower incidence of admission for unstable angina (17.9% versus 29.5%; P<.00001). The percentages of patients with a primary end point were 15.4% and 29.5% at 1 year, 23.5% and 36.6% at 2 years, and 31.7% versus 44.0% at 4 years (P=<.00001) in the invasive and conservative treatment groups, respectively. At 12 months, stable angina pectoris was present in 21% of patients in the invasive treatment group and 43% in the conservative treatment group. CONCLUSIONS: Invasive treatment in post-AMI patients with inducible ischemia results in a reduction in the incidence of reinfarction, fewer admissions due to unstable angina, and lower prevalence of stable angina. We conclude that patients with inducible ischemia before discharge who have received treatment with thrombolytic drugs for their first AMI should be referred to coronary arteriography and revascularized accordingly.

Platelet alloimmunization after transfusion. A prospective study in 117 heart surgery patients.

BACKGROUND AND OBJECTIVES: The frequency of platelet-specific antibodies after one series of blood transfusions has not been reported, and in multiply transfused patients is controversial. MATERIALS AND METHODS: We studied the frequency of alloimmunization against platelet antigens in 117 patients who received a single series of blood transfusions. They received mostly saline-adenine-glucose+mannitol red blood cell components (poor in leukocytes and platelets) in connection with cardiac surgery. Platelet-specific antibodies were detected with the platelet ELISA and the monoclonal-antibody-specific immobilization of platelet antigen assay. HLA antibodies were detected by the standard lymphocyte cytotoxicity techniques. RESULTS: We found platelet-specific anti-HPA-5b (anti-Bra) in 2 cases (1.7%). One antibody was the result of de novo immunization. We detected lymphocytotoxic HLA antibodies in 21 patients (17.9%), of whom 18 (15.4%) had had no detectable antibodies before transfusion. There was a positive correlation between the transfused load of immunogenic materials and the frequency of alloimmunization against HLA antigens. In one third of the immunized patients, there was no history of previous immunization. CONCLUSION: There was a low incidence of platelet-specific antibodies after one series of blood transfusions in this group of patients. This is similar to the results of some previous studies in multiply transfused patients, but not with those of others who found a higher incidence.

[Aortic dissection--a life-threatening condition requiring immediate treatment]. / Aortadissektion--en livstruende tilstand der kroever hurtig behandling.

We present a retrospective examination of 70 consecutive patients (median age 55 years, range 20-71 years) operated for aortic dissection from January 1981 to October 1992. Four of these patients were operated twice, making a total of 74 operations. The operations were grouped according to the Stanford classification in Type A-acute (53%), type A-chronic (11%), type B-acute (26%) and type B-chronic (10%). Fifty-seven patients were males (81%) and 90% of the operations were performed as emergencies. Eleven percent of the patients had Marfan Syndrome. The peroperative mortality was 23% and the perioperative mortality was 39%. The 10 year survival including the perioperative mortality was 39%. The frequency of operative complications lasting for more than one month was 12% and some of these complications were caused rather by the aortic disease rather than the operation. Further improvement depends on the referral of these patients to cardio-thoracic surgical units on near suspicion of the condition for the earliest possible treatment. Furthermore, patients must be followed lifelong for recurrences in progression of chronic AD.

Composite graft replacement of the aortic valve and ascending aorta with Cabrol technique.

Replacement of the aortic valve, root and ascending aorta with the technique first described by Cabrol was performed on 17 patients. In five cases the aortic arch was also replaced. The indications were type A aortic dissection with aortic insufficiency (8 cases, with acute dissection in 7), native endocarditis with severe aortic insufficiency and aortic root abscess (3 cases), prosthetic endocarditis (3), and true aneurysm of the ascending aorta with aortic insufficiency (3). Acute surgery was performed in 15 cases (88%). The overall operative mortality was 41%. For the patients discharged from hospital the mean observation time was 30 months. None died, but in one case the right leg of the interposition graft became occluded and reoperation was required 40 months after the primary operation for acute type A dissection. The described technique of aortic valve and root displacement can be used in all cases in which use of a composite graft is indicated, except in situations where the coronary ostia and arteries are damaged by acute dissection.

Accelerated cholesterol accumulation in homologous arterial transplants in cholesterol-fed rabbits. A surgical model to study transplantation atherosclerosis.

Accelerated coronary artery disease has become a major complication to heart transplantation in humans. Therefore, we have developed a surgical model in the rabbit, with transplantation of the thoracic aorta as a bypass graft onto the abdominal aorta of another rabbit. The model permits the study of cholesterol metabolism in transplanted arteries. The graft did not accumulate cholesterol for as long as 298 days, provided that the rabbits were normocholesterolemic, i.e., with plasma cholesterol levels of 0.3-0.7 mmol/l. However, after a few weeks of cholesterol feeding resulting in plasma cholesterol levels of 2-5 mmol/l, the homologous graft accumulated cholesterol compared with intact aortic tissue in the rabbits and also compared with autologous aortic grafts. The intimal clearance of plasma cholesteryl ester, mainly high density lipoprotein cholesteryl ester, in the luminal layer of the aortic graft was 60-150 nl x cm-2 x hr-1 1-2 hours after transplantation. The intimal clearance in the corresponding intact thoracic aorta of the recipient animal was 5-20 nl x cm-2 x hr-1. The values were 1,500-3,000 nl x cm-2 x hr-1 51-298 days after transplantation, while the intimal clearance of the rabbit's own aorta remained unchanged. A pronounced increase in plasma lipoprotein permeability is thus an early event in transplanted arteries. It results in a higher cholesteryl ester influx that leads to cholesterol accumulation in the artery, but only if the rabbits are fed a cholesterol-enriched diet. This rabbit model may be useful in the search for interventional measures to prevent or diminish the accelerated coronary artery disease in transplanted hearts in humans.

Procainamide conversion of acute atrial fibrillation after open-heart surgery compared with digoxin treatment.

In 30 patients who developed atrial fibrillation after open-heart surgery the efficacy of intravenous procainamide was evaluated and compared with standard acute digoxin digitalisation. The patients were randomized to two groups of 15. One group received procainamide intravenously at a rate of 25 mg/min and with maximum dose 15 mg/kg. In the other group digoxin 0.75-1.0 mg was given intravenously according to renal function and body weight. Conversion to sinus rhythm occurred during or immediately after the infusion in 87% of the procainamide group, but only in 60% of the digoxin group (p < 0.05). The mean time from start of treatment to conversion was 40 min in the procainamide vs. 540 min in the digoxin group (p < 0.002). There were no serious complications of the procainamide treatment. Intravenous procainamide conversion of postoperative atrial fibrillation is concluded to be effective and safe and can be recommended as the treatment of first choice in awake and nonintubated postoperative cardiac patients.

Repeat coronary artery bypass grafting.

In 1981-1989 we performed repeat coronary artery bypass grafting on 42 men and 10 women (mean age 55 years) with angina pectoris recurring on average 27 months after the primary operation. The cause was occlusion or stenosis of vein grafts alone (59%) or in combination with progression of native coronary atherosclerosis (31%) or progression in the native circulation without graft failure (10%). Complications at the repeat operation included five lesions of the right ventricle and five lesions of patient grafts. The 30-day mortality was 3.8% (95% confidence limits 0.5-13.2%). Survival after observation averaging 2 1/2 years was 92.3% (95% confidence limits 81.5-97.9%). Angina pectoris was completely relieved after the operation in 48% of the patients, lessened in 35% and unchanged in 17%. Although repeat coronary artery bypass grafting carries heightened mortality and morbidity, and the results are less satisfactory than after first-time bypass, the operation can be worthwhile.

An experimental study of hot air thermocoagulation in cardiac surgery.

Recently a thermocoagulator using hot air has been developed. It has been used for haemostatic purposes in a number of cases of liver, pulmonary and retroperitoneal cancer surgery. An experimental animal study was undertaken to evaluate the use of the thermocoagulator during cardiac surgery. Since the thermocoagulator produces coagulation necrosis, the epi-/myocardium including the epicardial coronary arteries was investigated microscopically for acute and chronic histopathological changes. The investigation demonstrated that the thermocoagulator is an effective hemostatic tool during cardiac surgery. The histological examination of the hearts has shown that the technique does not damage the myocardium or the coronary arteries neither at the time of application nor in the long term.

Aneurysm of the ductus arteriosus. A review of the literature and the surgical implications.

One hundred and forty-four cases of aneurysms of the ductus arteriosus (DAA) have been reported in the literature of which 106 appeared spontaneously and 38 followed surgical treatment of a patent ductus arteriosus (PDA). Within the last few years there has been an increasing number of reported spontaneous DAA. However, the real incidence is presumably still underestimated. Aortography is a well established diagnostic method. In neonates, transthoracic echocardiography has shown convincing potential, whereas in older children and adults, transoesophageal echocardiography has yielded very promising results. Serious complications following spontaneous DAA are rupture, erosion, infection and thromboembolism. In infants younger than 2 months of age, the complication rate is 31%, in children between 2 months and 15 years, 66%, in adults, 47%. The rate of complications following postoperative DAA is even higher: 91% of the unoperated cases died due to rupture or infection. The operative mortality in children older than 2 months and adults is low. In the neonate group, 2 of 8 died during operation. The operative mortality in patients with postoperative DAA was 26%. Based on information from the literature, we suggest prompt surgical treatment of all spontaneous DAA in patients older than 2 months of age, and in all patients with postoperative DAA. In infants, a DAA should be closely followed with echocardiography, as spontaneous regression has been reported in this age group. If no regression is seen within a few days, it should be surgically corrected.

[Surgical treatment of cancer of the cardia and the esophagus]. / Kirurgisk behandling af cancer cardiae og cancer esophagi.

During the period 1977 to 1989, 379 patients with cancer cardiac and cancer esophagi were admitted. The ages ranged from 18-88 years with an average of 65 years. The treatment concept was basically unchanged during the study period. Resection as described by Ivor Lewis was employed as palliative or curative treatment when resection was considered possible. Intubation of the esophagus was employed when no other treatment was considered possible. Resection was employed in 251 patients, eight of these emergencies on account of perforation or haemorrhage. Bypass operations were employed in five patients, intubations in 63 and no surgical treatment was undertaken in 60 patients. The all over operative mortality for resections was 11.2% and for elective operations 9.9%. The operative mortality increased with the TNM stage of the tumour and was 3.2% for stages I + II, 8.2% for stage III and 24.4% for stage IV. The complication ration was 42%. 15% of the patients submitted to resection required reoperation. Anastomotic leaks were encountered in 18 patients and nine of these died. Pulmonary complications were the most frequent and resulted in ten early postoperative deaths. The mortality connected with intubations was 15%. The over all five-year survival rate after resections was 10.4%. In stages I + II this was 42% and 8% in stage III. None of the patients in stage IV survived for two years. The longest survival after intubation was less than one year.

[Reoperation because of mechanical heart valve prosthesis dysfunction]. / Reoperation på grund af dysfunktion af mekaniske hjerteklapproteser.

Thromboembolism, haemolysis, prosthetic endocarditis and paravalvular leakage are the commonest complications of introduction of mechanical heart valve prosthesis. Malfunction of the cusps inside the sewing ring is a rare but serious condition, which is due to partial or total prevention of the free movements of the cusps or valves resulting in symptoms of valvular stenosis or incompetence. Twenty-six valvular prosthesis (2.3%) were replaced on account of malfunction. Fifteen out of the 26 patients were submitted to emergency operation and 11 to elective intervention. Four out of the 26 patients died preoperatively or during the postoperative course, corresponding to a lethality of 15%. The operative lethality was associated with emergency operations exclusively. The authors conclude that patients with previously well functioning valvular prosthesis who develop symptoms of cardiac failure should be referred to the cardiological centre where the operation was carried out as rapidly as possible instead of institution of traditional medical treatment.

Different efflux pathways for high and low density lipoproteins from porcine aortic intima.

To study the efflux of high (HDL) and low (LDL) density lipoproteins from the arterial wall in vivo, a surgical model in pigs was used. An isolated segment of the lesion-free thoracic aorta was pulse labeled from the lumen of the artery with 3H-cholesteryl ester labeled HDL and 14C-cholesteryl ester labeled LDL. Subsequently, the labeled aortic segment was exposed to cold chase in vivo. The transfer of HDL cholesteryl ester from plasma into intima expressed as intimal clearance was three to seven times greater than that of LDL cholesteryl ester. At least 50%, but possibly as much as 95%, of the HDL cholesteryl ester that entered the arterial intima during a period of 4 hours penetrated the arterial wall beyond the internal elastic lamina. In contrast, less than 15% of the LDL cholesteryl ester that entered the arterial intima in the same period penetrated beyond the luminal layer. After 24 hours of cold chase in vivo, more than 80% of both labeled HDL esterified cholesterol and labeled LDL esterified cholesterol had disappeared from the arterial wall. Transmural profiles after 9 hours of cold chase showed that labeled HDL was present throughout the entire arterial wall, whereas labeled LDL in quantitative amounts was present only in the luminal layer. The results suggest that the most important efflux route for HDL esterified cholesterol is through the vasa vasorum and lymphatics in the outer media and adventitia, whereas LDL esterified cholesterol predominantly leaves intima via the lumen of the artery.