Jeffrey M. Piehler

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.

Postsurgical Stage I Bronchogenic Carcinoma: Morbid Implications of Recurrent Disease

Three hundred forty-six patients with post-surgical non-small cell Stage I bronchogenic carcinoma were followed from 5.0 to 10.8 years (median, 7.0 years). Recurrent cancer developed in 135 patients (39%). Seventy-five recurrences were nonregional metastases (55.6%); 35 (25.9%), a subsequent primary lung cancer; and 25 (18.5%), local recurrence only. The rate of recurrent lung cancer decreased from 15.0 patients per 100 patient-years the first postoperative year to 2.3 the seventh and subsequent years. The rate of recurrence varied among the three different types of recurrent cancer. Five years after pulmonary resection, 70.0% of patients with T1 N0 neoplasms had no evidence of recurrence compared with 58.2% of patients with T2 N0 tumors (p = 0.012) and only 31.8% of patients with T1 N1 neoplasms (p less than 0.001). There was no significant difference in overall rate of recurrence among the various cell types. Currently, 174 patients are alive. Lung cancer survival (Kaplan-Meier) was 69.1% at 5 years and 61.9% at 9 years. At 2 years following detection of subsequent lung cancer, 51.8% of patients with subsequent primary lung cancer had survived lung cancer compared with 23.4% for those with local recurrence and only 8.9% for those with nonregional metastases.

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.

Platypnea-Orthodeoxia: Clinical Profile, Diagnostic Workup, Management, and Report of Seven Cases

Platypnea-orthodeoxia is a rare and poorly understood syndrome of orthostatic accentuation of a right-to-left shunt, usually across a patent foramen ovale. The syndrome is most commonly recognized in patients with a history of a major pulmonary disorder such as pneumonectomy, recurrent pulmonary emboli, or chronic lung disease. Pulmonary artery pressures are typically normal. The physiologic mechanism is unknown. We recommend that initial assessment consist of measurement of blood gases with the patient in the supine and upright positions. Orthostatic desaturation should prompt further investigation. A definitive diagnosis can most easily be obtained by tilt-table two-dimensional echocardiography with peripheral venous contrast medium. The shunt can be localized at the atrial level and directly visualized and semiquantitated. The decision about surgical closure of the patent foramen ovale is based on the degree of clinical disability. Because a significant shunt is manifest only in the upright position, astute clinical suspicion is of paramount importance for proper diagnosis. Increased awareness of this syndrome and ease of echocardiographic diagnosis will facilitate recognition of this potentially treatable cause of orthostatic hypoxia.

Bronchogenic Carcinoma with Chest Wall Invasion: Factors Affecting Survival Following en Bloc Resection

Sixty-six patients (54 men and 12 women) with primary bronchogenic carcinoma and documented chest wall invasion underwent en bloc chest wall and pulmonary resection at the Mayo Clinic between January 1, 1960, and January 1, 1980. Ages ranged from 36 to 85 years, with a mean of 62.2. Forty-eight lobectomies, 16 pneumonectomies, and 2 wedge excisions were performed. After operation, 31 patients were classified as T3 N0 M0, 7 as T3 N1 M0, and 12 as T3 N2 M0. In 16 patients, the N classification could not be determined (T3 Nx M0). Operative mortality was 15.2%. Actuarial five-year survival (Kaplan-Meier method) of the 56 patients surviving operation was 32.9%. Five-year survival for patients with T3 N0 M0 neoplasms was 53.7%; five-year survival for patients with N1 and N2 neoplasms was only 7.4% (p = 0.001). The effect of various factors on survival, both singularly and in combination, was assessed by Coxs proportional hazards model. Only age had a significant association with survival. Among patients with T3 N0 M0 neoplasms, five-year survival was 84.6% for those 60 years of age or less and 27.7% for patients who were older than 60 years (p = 0.009). We conclude that en bloc resection for primary bronchogenic carcinoma with chest wall invasion, while associated with a significant mortality, can be performed with a strong likelihood of long-term survival if regional lymph nodes are not metastatically involved and there is no evidence of distant metastasis.

Primary Chest Wall Tumors: Factors Affecting Survival

Between 1955 and 1975, chest wall resection was done in 90 patients for primary chest wall tumors. Ages ranged from 8 to 96 years (mean, 44.3 years). A painful mass was the most common sign and symptom. Eighty-two tumors (91.1%) were located in the lateral chest wall and eight, in the anterior thorax. The tumor was malignant in 71 patients (78.9%) and benign in 19. All patients with benign tumors had complete excision and are currently free from disease. Malignant fibrous histiocytoma, chondrosarcoma, and rhabdomyosarcoma constituted 62% of the malignant neoplasms. Most malignancies were treated by wide resection. There were no thirty-day operative deaths. Overall 1-, 5-, and 10-year survival was 89%, 57%, and 49%, respectively. Recurrent tumor developed in 37 patients (52%); 5-year survival, however, was only 17% after recurrence. Cell type and extent of invasion significantly influenced survival. Both chondrosarcoma and rhabdomyosarcoma had a better prognosis than malignant fibrous histiocytoma (p less than 0.05). We conclude that early resection is the treatment of choice for primary malignant chest wall tumors and that development of recurrent disease is an ominous event.

Chondrosarcoma of the Chest Wall: Factors Affecting Survival

The cases of 96 patients (55 male and 41 female) with primary chondrosarcoma of the chest wall were reviewed. Ages ranged from 17 to 78 years (median, 53.5 years). The tumor involved the rib in 78 patients and the sternum in 18. Seventy-two patients had treatment at the Mayo Clinic, 28 by wide resection, 25 by local excision, and 19 by palliative excision. There was 1 operative death. Follow-up ranged from 1 to 46 years. Recurrent chondrosarcoma developed in 37 patients. All had local recurrence, and 14 also had metastases. Within 10 years, recurrence had developed in 50% of patients who had local excision and in 17% of patients who had wide resection. Ten-year chondrosarcoma survival (Kaplan-Meier) for patients treated by wide resection was 96%; by local excision, 65%; and by palliative excision, 14% (p less than 0.0001). Tumor grade, tumor diameter, tumor location, and date of operation all had a significant influence on survival. This report documents the natural history of chest wall chondrosarcoma and demonstrates that early wide resection is the treatment of choice.

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.

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.