James R. Pluth

A Platelet-Inhibitor-Drug Trial in Coronary-Artery Bypass Operations: Benefit of Perioperative Dipyridamole and Aspirin Therapy on Early Postoperative Vein-Graft Patency

To prevent occlusion of aortocoronary-artery-bypass grafts, we conducted a prospective, randomized-double-blind trial comparing dipyridamole (instituted two days before operation) plus aspirin (added seven hours after operation) with placebo in 407 patients. Vein-graft angiography was performed in 360 patients (88 per cent) within six months of operation (median, eight days). Within one month of operation, 3 per cent of vein-graft distal anastomoses (10 of 351) were occluded in the treated patients, and 10 per cent (38 of 362) in the placebo group; the proportion of patients with one or more distal anastomoses occluded was 8 per cent (10 of 130) in the treated group and 21 per cent (27 of 130) in th placebo group. This benefit in graft patency persisted in each of over 50 subgroups. Early postoperative bleeding was similar in the two groups. In this trial dipyridamole and aspirin were effective in preventing graft occlusion early after operation.

Effect of Dipyridamole and Aspirin on Late Vein-Graft Patency after Coronary Bypass Operations

To study the prevention of occlusion of aortocoronary-artery bypass grafts, we concluded a prospective, randomized, double-blind trial comparing long-term administration of dipyridamole (begun two days before operation) plus aspirin (begun seven hours after operation) with placebo in 407 patients. Results at one month showed a reduction in the rate of graft occlusion in patients receiving dipyridamole and aspirin. At vein-graft angiography performed in 343 patients (84 per cent) 11 to 18 months (median, 12 months) after operation, 11 per cent of 478 vein-graft distal anastomoses were occluded in the treated group, and 25 per cent of 486 were occluded in the placebo group. The proportion of patients with one or more distal anastomoses occluded was 22 per cent of 171 patients in the treated group and 47 per cent of 172 in the placebo group. All grafts were patent within a month of operation in 94 patients in the placebo group and 116 patients in the treated group; late development of occlusions was reduced from 27 per cent in the placebo group to 16 per cent in the treatment group. The results show that dipyridamole and aspirin continue to be effective in preventing vein-graft occlusion late after operation, and we believe that such treatment should be continued for at least one year.

Trial of combined warfarin plus dipyridamole or aspirin therapy in prosthetic heart valve replacement: Danger of aspirin compared with dipyridamole

Despite the use of oral anticoagulation in patients with prosthetic heart valves, persistent thromboembolism over time warrants a search for improved methods of prevention. Thus, patients receiving 1 or more mechanical prosthetic heart valves were randomized to therapy with warfarin plus dipyridamole (400 mg/day) or warfarin plus aspirin (500 mg/day) on the basis of location and type of valve and surgeon, and followed up with a concurrent, nonrandomized control group taking warfarin alone. In 534 patients followed up 1,319 patient-years, excessive bleeding (necessitating blood transfusion or hospitalization) was noted in the warfarin plus aspirin group (23 of 170 [14%], or 6.0/100 patient-years) compared with warfarin plus dipyridamole (7 of 181 [4%], or 1.6/100 patient-years, p less than 0.001), or warfarin alone (9 of 183 [5%], or 1.8/100 patient-years, p less than 0.001). A trend was evident toward a reduction in thromboembolism in the warfarin plus dipyridamole group (2 of 181 [1%], or 0.5/100 patient-years) as compared with warfarin plus aspirin (7 of 170 [4%], or 1.8/100 patient-years), or warfarin alone (6 of 183 [4%], or 1.2/100 patient-years). Adequacy of anticoagulation (based on 12,720 prothrombin time determinations) was similar in all 3 groups with 65% of prothrombin times in the therapeutic range (1.5 less than or equal to prothrombin time/control less than or equal to 2.5), 30% too low, and 5% too high. Warfarin plus aspirin therapy resulted in excessive bleeding and is contraindicated. Longer follow-up study is needed to determine whether further separation of the incidence of thromboembolism can be detected.

High risk of thromboemboli early after bioprosthetic cardiac valve replacement

OBJECTIVES We studied the rate of thromboembolism in patients undergoing bioprosthetic replacement of the aortic or mitral valve, or both, at serial intervals after operation and the effects of anticoagulant or antiplatelet treatment and risk factors. BACKGROUND Thromboembolism appears to occur early after operation, but the incidence, timing and risk factors for thromboembolism and the role, timing, adequacy, effectiveness, duration and risk of anticoagulation and antiplatelet agents are uncertain. METHODS The rate of thromboembolism was studied at three time intervals after operation (1 to 10, 11 to 90 and > 90 days) in 816 patients who underwent bioprosthetic replacement of the aortic or mitral valve, or both, at the Mayo Clinic from January 1975 to December 1982. The effect of antithrombotic therapy (warfarin, aspirin or dipyridamole, alone or in combination) was evaluated. RESULTS Median follow-up of surviving patients was 8.6 years. The rate of thromboembolism (%/year) decreased significantly (p < 0.01) at each time interval after operation (1 to 10, 11 to 90 and > 90 days) for mitral valve replacement (55%, 10% and 2.4%/year, respectively) and over the first time interval for aortic valve replacement (41%, 3.6% and 1.9%/year, respectively). During the first 10 days, 52% to 70% of prothrombin time ratios were low (< 1.5 x control). Patients with mitral valve replacement who received anticoagulation had a lower rate of thromboembolism for the entire follow-up period (2.5%/year with vs. 3.9%/year without anticoagulation, p = 0.05). Of 112 patients with a first thromboembolic episode, permanent disability occurred in 38% and death in 4%. Risk factors for emboli were lack of anticoagulation, mitral valve location, history of thromboembolism and increasing age. Only 10% of aortic, 44% of mitral and 17% of double valve recipients had anticoagulation at the time of an event. Patients with bleeding episodes (2.3%/year) were older and usually underwent anticoagulation. Blood transfusions were required in 60 of 111 patients (1.2%/year), and 13 patients (0.3%/year) died. CONCLUSIONS Thromboembolic risk was especially high for aortic and mitral valve replacement for 90 days after operation, and overall was increased with lack of anticoagulation, mitral valve location, previous thromboembolism and increasing age. Anticoagulation reduced thromboemboli and appears to be indicated in all patients as early as possible for 3 months and thereafter in those with risk factors, but needs prospective testing.

Temporal Changes in the Causes of Aortic Stenosis: A Surgical Pathologic Study of 646 Cases

Among 646 patients with pure aortic stenosis who underwent valve replacement at our institution between 1981 and 1985, the three most frequent causes were calcification of congenitally bicuspid aortic valves (38%), degenerative (senile) calcification of tricuspid aortic valves (33%), and postinflammatory (presumably rheumatic) calcification and fibrosis (24%). Among the 324 patients younger than 70 years of age, calcified bicuspid valves were observed in 50%. In contrast, among 322 patients 70 years of age or older, degenerative calcification accounted for 48% of the stenotic aortic valves. During the 5 years of the study, the relative frequency of postinflammatory disease decreased from 30% to 18%, and that of bicuspid valves decreased from 37% to 33%. In contrast, the relative frequency of degenerative calcification increased from 30% to 46%. Consequently, degenerative (senile) calcification is currently the most common cause of aortic stenosis among patients undergoing valve replacement at our institution. This finding may be related to changes in life expectancy in the general population, alterations in patient referral practices, and an increased willingness of surgeons to operate on older patients. Regardless of cause, the observed temporal changes in etiologic factors for aortic stenosis may indicate a potential source of increasing health-care costs among the elderly population.

Permanent pacemaker infections: Characterization and management

From January 1974 to June 1980, a total of 46 patients were treated for infections involving permanent pacing systems. Demographic characteristics, types of infecting organisms, specific clinical features, significance of an infected foreign body and various medical and surgical treatment methods are described. Likely infecting organisms depend on the mode of presentation and the time course of the infection. Optimal treatment for the large majority of patients requires removal of the entire infected pacing system. In a subgroup of patients, a short course of antibiotic therapy followed by one stage surgery involving implantation of a new pacing system and concurrent explanation of the infected pacemaker was used safely with excellent results.

Long-term follow-up of isolated replacement of the aortic or mitral valve with the Starr-Edwards prosthesis.

Review of 1,684 cases of isolated aortic or mitral valve replacement with a Starr-Edwards prosthesis demonstrated that the procedure provides improved life expectancy over that found in the natural history of valvular heart disease. Further improvement in results depends on continued reduction in operative and late mortality and in the incidence of thromboembolism. Advanced preoperative functional class, atrial or ventricular enlargement, a history of prior heart surgery, advanced age at operation and untreated valvular disease were among the factors related to increased early or late mortality. The data suggest that adequate anticoagulation, earlier performance of valve replacement and more complete repair of valvular dysfunction may increase survival rates.

Reoperation on prosthetic heart valves: Patient-specific estimates of in-hospital events

Reoperation on prosthetic heart valves is increasingly under consideration for both clinical and prophylactic indications. To determine the correlates of hospital events, including in-hospital mortality, new persisting neurologic deficit, and length of postoperative stay, a three-institution study of 2246 consecutive prosthetic valve reoperations performed on 1984 patients between 1963 and 1992 was undertaken. The combined experience ranged from high-risk patients coming moribund to the operating room to an important number of well individuals undergoing prophylactic reoperations on potentially failing valves. The risk-unadjusted hospital mortality was 10.8%, neurologic deficit at hospital discharge 1.1%, and length of stay 10 days (median). Multivariably determined correlates of outcome included age at reoperation, degree, severity, and acuity of impairment of cardiac function, extensiveness of valvular heart disease, coexisting morbid conditions, number of previous heart operations, and concomitant procedures. The risk-adjusted hospital mortality for the first elective reoperation in a good-risk patient was 1.3% (90% confidence limits 0.3% to 4.4%), neurologic deficit 0.3% (90% confidence limits 0.02% to 1.8%), and length of postoperative stay 7 days (90% confidence limits 4 to 13), emphasizing the wide variance in outcome events. Equations were developed to permit wide application of the results of the study for quantitatively estimating the risk of outcome events based on individual preoperative patient characteristics. These estimates should be useful for informed patient consent, considerations of prophylactic valve replacement, and cost and resource use.

Postinfarction Ventricular Septal Rupture Surgical Considerations and Results

Twenty-two patients had ventricular septal rupture complicating acute myocardial infarction. Sixteen of the 22 patients underwent surgical repair. The clinical findings, catheterization data, and operative results suggest that closure of the rupture should be delayed when possible from three to six weeks after the infarction to allow firm fibrous healing of the region. When surgery is thus delayed, the operative risks are smaller and the long-term results are good.

Early and late results following repair of dissections of the descending thoracic aorta

Management of dissections of the descending thoracic aorta remains controversial, especially with regard to timing and method of repair. To clarify these and other issues we have reviewed our total experience with repair of descending aortic dissections between 1962 and 1983. The 44 men and 20 women had a mean (+/- SEM) age of 59 +/- 2 years (range, 19 to 83 years), and in all patients the dissection originated in and was limited to the aorta distal to the left carotid artery (Stanford type B, DeBakey types IIIa and IIIb). Twenty-nine patients underwent operation within 2 weeks of the onset of symptoms (acute), and the remainder had later repair (chronic). During repair, circulation distal to the aortic cross-clamp was supported with cardiopulmonary bypass or shunt in two thirds of patients. Overall, 18 deaths occurred less than or equal to 30 days postoperatively (operative risk 28%), and risk was higher in acute (45%) than in chronic (14%) dissections. Operative risk was not significantly related to protection of the distal circulation. The most serious postoperative complication was spinal cord ischemia manifested by paraplegia in five patients (8%) and transient or permanent paraparesis in six patients (9%). Risk of spinal cord ischemia was significantly lower in patients who had protection of the distal circulation during operative repair (8% vs. 44%, p = 0.003). Late survival, including hospital deaths, was 49% +/- 7% at 5 years after operation; 22 of the 46 patients who survived repair were found to have aneurysms involving the thoracic and/or abdominal segments of the aorta. Our results indicate that repair of chronic dissection of the thoracic aorta has a lower operative risk than repair of acute dissections, and initial medical management of acute dissection may be indicated if no early complications occur. Risk of spinal cord ischemia is significantly reduced by cardiopulmonary bypass or shunt and is preferred over aortic cross-clamping alone. Finally, these patients require careful long-term follow-up because of the high incidence of residual or recurrent aortic aneurysms.