A prospective randomized study of prophylactic OKT3 versus equine antithymocyte globulin after heart transplantation--increased morbidity with OKT3.

The aim of this study was to compare the efficacy and toxicity of prophylactic OKT3 and equine antithymocyte globulin when each drug was administered for a similar duration after heart transplantation. Forty-one patients (35 males, 6 females; mean age 46 +/- 2 years) were randomized to receive either OKT3 for 10 days (20 patients) commencing within 24-48 hr of transplantation or ATGAM for 8 days (21 patients) commencing on the day of transplantation. All patients were maintained on triple-agent immunosuppression with prednisolone, azathioprine, and cyclosporine. The two groups were well matched with respect to age, sex distribution, pretransplant cardiac diagnosis, and donor heart ischemic time. Mean duration of follow-up was 14 months (range 9-19 months): Actuarial survival at 12 months was 83 +/- 9 in the OKT3 group and 81 +/- 9 in the ATG group (P = NS). Mean time to first cardiac rejection was 33 +/- 8 days in the OKT3 group compared with 27 +/- 5 days in the ATG group (P = NS). Linearized rejection rate did not differ between the two groups at any time point up to 12 months posttransplant. Viral infections were significantly more common in the OKT3 group: 1.6 +/- 0.3 vs. 0.8 +/- 0.2 infections per patient (P < 0.05). Adverse reactions were more common in patients who received OKT3 prophylaxis and included three patients who developed acute respiratory distress, two of whom required assisted ventilation. In conclusion, prophylactic OKT3 and ATGAM result in comparable rejection rates and survival when administered for a similar duration after cardiac transplantation. OKT3, however, is associated with increased morbidity due to a higher incidence of adverse reactions and of viral infections. These findings suggest that ATGAM is the more suitable cytolytic agent for rejection prophylaxis after heart transplantation.

Long-term results of tricuspid valve replacement and the problem of prosthetic valve thrombosis.

Observations in 71 patients having tricuspid valve replacement over a 14-year period are described. The operative mortality rate was 10% and the actuarial survival rate was 73% at 5 years and 47% at 10 years. Survival was unaffected by the number of valves replaced or the type used (27 Starr-Edwards, 32 Björk-Shiley, 8 Lillehei-Kaster, and 4 porcine xenografts). Complications were common: 3 deaths were related to anticoagulation and 1 was due to a systemic embolus. Six patients required permanent pacing. There was a very high incidence of thrombosis of the prosthetic tricuspid valve. Twenty percent of the tilting disc valves thrombosed, compared with 4% of the Starr-Edwards valves (p less than 0.05). Symptoms of thrombosis were usually insidious, and its diagnosis was often delayed. There was a continuing risk of this complication, and presentation occurred up to 12 years after the original operation. Thrombolytic therapy with streptokinase was successful in 1 of 2 patients. Replacement of the thrombosed prosthetic valves was carried out without mortality in 8 patients.

Randomized controlled trial of intraaortic balloon counterpulsation in early myocardial infarction with acute heart failure.

The value of intraaortic balloon counterpulsation in limiting infarct size and improving survival was studied in patients with early transmural myocardial infarction complicated by acute heart failure. Thirty such patients, previously well, were randomly assigned to counterpulsation (14 patients) or standard therapy (16 patients). Counterpulsation was begun 4.8 to 13.7 hours (mean 7.1) after the onset of pain and continued for less than 1 to 11 days (mean 4.5). Peak creatine kinase was 1,794 +/- 846 IU/liter (mean +/- standard deviation) in patients receiving counterpulsation compared with 1,688 +/- 908 for those receiving standard therapy; cumulative creatine kinase was 3,590 +/- 1,936 IU/liter for patients receiving counterpulsation and 2,945 +/- 1,803 for those receiving standard therapy. Hospital mortality was similar (counterpulsation, 7 of 14; standard therapy, 7 of 16 [p = 0.05 for 25 percent mortality reduction]) as was mortality at follow-up (counterpulsation, 8 of 14; standard therapy, 10 of 16 [p = 0.09 for 25 percent mortality reduction]). Functional class at follow-up examination 1 to 36 months (mean 15) after infarction was also similar in the two groups. Counterpulsation did not appear to modify infarct size or to alter morbidity or mortality when initiated as primary therapy 4.8 to 13.7 hours after the onset of symptoms of myocardial infarction.

Postinfarction cardiac rupture.

This paper records an experience of 42 cases of cardiac rupture or syndromes simulating rupture. These include free wall rupture, hemopericardium without rupture, septal rupture associated with free wall rupture, pseudoaneurysm, and septal rupture. These groups constitute a series of syndromes with many features in common in terms of clinical presentation, difficulty in assessment, timing of operative intervention, and operative management. Free wall rupture, which can be simulated by hemopericardium without rupture, is not always rapidly fatal. Successful intervention was achieved in six of the 13 cases in the free wall group. Ventricular septal defect occurs less frequently than free wall rupture, is more easily diagnosed, and less frequently requires urgent medical intervention. In 12 of the 14 cases of acute rupture, stabilization of the patient by conservative measures could not be achieved and operation was undertaken within 1 week of infarction. There were seven survivors, in four of whom the defect reopened, with successful reoperation in three. In the remaining 15 cases, stabilization by conservative measures was achieved and operation was delayed until at least 2 weeks after infarction. There were 14 survivors and only one instance of reopening of the defect.

Reduction of bacteria on pork carcasses associated with chilling method.

In addition to reducing the temperature of pork carcasses immediately after slaughter and before fabrication, blast chilling (snap chill) or conventional chilling can reduce bacterial populations associated with fresh meats. However, there is little information on bacteria survival resulting from the freeze or chill injury of meat products. In this study, porcine fecal slurries with and without pathogens (Listeria monocytogenes, Salmonella Typhimurium, and Campylobacter coli) were inoculated onto skin-on and skin-off pork surfaces and subjected to industry-specific blast or conventional chilling conditions. A thin agar layer method was used for the recovery of freeze- or chill-injured cells. Test results indicated that there were no statistically significant (P > 0.05) differences between blast and conventional chilling treatments with respect to the reduction of high and low inoculation levels of mesophilic aerobic bacteria, total coliforms, or Escherichia coli on either skin-on or skin-off surfaces. Chilling treatments did not differ significantly (P > 0.05) with respect to their ability to reduce low (3 log10 CFU/cm2) levels of L. monocytogenes and Salmonella Typhimurium. However, C. coli was reduced to undetectable levels, even after enrichment, on pork surfaces inoculated with low levels (3 log10 CFU/cm2) and subjected to blast chilling. Blast and conventional chilling treatments were more effective against all pathogenic bacterial populations when pork surfaces where inoculated at high levels (5 log10 CFU/cm2). The effects of chilling techniques on microbial populations could provide pork processors with an additional intervention for pork slaughter or information to modify and/or improve the chilling process. The information obtained from this study has the potential to serve as a means of producing a microbiologically safer product.

Comparison of recovery methods for freeze-injured Listeria monocytogenes, Salmonella Typhimurium, and Campylobacter coli in cell suspensions and associated with pork surfaces.

Cells injured as a result of freezing, heating, and acidification treatments may not grow during conventional microbiological procedures owing to the presence of selective agents, compounds, or dyes in the media, impairing the cell's ability to repair itself and grow. Injured cells can be recovered by combining selective and nonselective media into a single system. With such combinations, the diffusion of the selective compounds or dyes is controlled, allowing for the resuscitation of injured cells of interest while also inhibiting the growth of undesirable background microflora. In this study, Listeria monocytogenes, Salmonella Typhimurium, and Campylobacter coli suspended in buffer or associated with pork surfaces were subjected to a freeze-thaw cycle (-15 degrees C for 24 h, 4 degrees C for 4 h). Following treatments, freeze-injured cells were plated on appropriate media for the overlay (OV), thin agar layer (TAL), and Lutri plate (LP) recovery methods. The levels of L. monocytogenes and Salmonella Typhimurium recovered from cell suspensions and pork surfaces by the TAL, OV, and LP methods following freeze treatments were not statistically different (P > 0.05) from recovery levels associated with nonselective media. Conversely, levels of pathogens on selective media were significantly reduced compared with those for the other methods employed. The TAL method's recovery of C. coli was not significantly different from that achieved with the nonselective media. Overall, the results presented in this study demonstrate that the TAL method not only was easier to perform, but also allowed improved isolation of single colonies for further characterization. This study may provide researchers with better methods to determine the effectiveness of industry-employed chilling processes in reducing pathogenic bacteria associated with red meat surfaces.

Thrombolytic therapy for a thrombosed Bjork-Shiley tricuspid valve prosthesis.

A 67-year-old mand in whom mitral and tricuspid Bjork-Shiley tilting disc prostheses had been implanted 68 months previously presented with thrombotic obstruction of his tricuspid prosthesis. Initial cardiac catheterization demonstrated a significant transprosthetic tricuspid diastolic gradient (9.5 mmHg) with a calculated prosthetic valve orifice area (0.62 cm2) indicating a critical degree of stenosis. The resting cardiac index was markedly reduced (1.5 l/m2/min). Following an intravenous infusion of streptokinase for 66 hours, repeat cardiac catheterization revealed a 50% reduction in transprosthetic diastolic gradient across the tricuspid valve (4.7 mmHg), a greater than fourfold increase in prosthetic valve orifice area (2.87 cm2) with a normal resting cardiac index (3.1 l/m2/min).

Effects of low-dose cyclosporine A on toxicity and rejection in cardiac transplantation.

In conclusion, the low doses of CsA have significantly reduced nephrotoxicity and infectious complications. The patient survival has been acceptable, but there has been a disappointing incidence of rejection and graft loss in patients who have survived the first 3 months. We feel our experience would indicate that by targeting our CsA dosages to such low serum levels some of our patients receive suboptimal immunosuppression. Perhaps the best way of overcoming this is add a third maintenance immunosuppressive agent such as azathioprine to supplement immunosuppression. In fact, we have now changed our immunosuppressive protocol to include azathioprine while maintaining our CsA therapy at its current level.

Coronary artery surgery in Asian patients.

We studied retrospectively, 412 consecutive Asian patients undergoing coronary artery bypass grafting between January 1st, 1982 and June 30th, 1987. The mean age was 55 +/- 9 years at operation with a 70.5% male predominance. Patients of Chinese origin accounted for 60.9%, Indonesian for 26.4%, Indian 9.9% and Malaysian 2.6%. Chronic stable angina was the most consistent presenting symptom in 71% and 49% had at least one myocardial infarction in the past. Fifty percent were hypertensive and 26% diabetic. Left main stem coronary artery obstruction was evident in 21.6% and the coronary arteries diffusely diseased in 53%. An average of 3.8 +/- 0.4 grafts were performed per patient using reversed saphenous vein, and endarterectomies were necessitated in 27.1%. The small calibre of coronary arteries in Asian patients was reflected by 54% of grafted vessels having a luminal diameter of 1.5 mm. The early mortality rate and the peri-operative myocardial infarction rate was 1.2% in each instance. A mean follow-up of 30 months revealed a late mortality of 1.9% and 76% of patients were in NYHA Functional Class I. This study suggests that despite a high incidence of hypertension, diabetes and diffuse coronary artery disease Asian patients tolerate coronary artery bypass graft surgery well and obtain significant benefit from it.

Myocardial revascularisation in patients over seventy five years.

A consecutive series of 73 patients aged 75 years and above underwent coronary artery bypass graft surgery during a 6 year period. Pre-operatively unstable angina (61.6%) and congestive heart failure (10.9%) were significant presenting features. Triple vessel disease accounted for 61.6% of cases while 26% had left main coronary obstruction. The mean number of grafts per patient was 3.2 +/- 0.9. Combined procedures such as valve replacement were done in 16.2% of patients. The hospital mortality rate was 2.7% and there was not a single recordable case of peri-operative myocardial infarction. Significant complications post-operatively were atrial arrhythmias (43.8%), segmental pulmonary atelectasis (43.8%) and renal problems (15%). Of the sixty patients followed up at an average of 27.7 months, 58 were in NYHA Functional Class I. Good patient selection and careful monitoring leads to encouraging results with coronary artery bypass grafting in the elderly.

The Bentall procedure: a surgical option in Ehlers-Danlos syndrome.

The Ehlers-Danlos syndrome (EDs) is one of the most frequently encountered inherited disorders of connective tissue. The arterial-ecchymotic type IV is notorious for large vessel involvement associated with spontaneous catastrophic bleeding. Most of these patients who require cardiovascular surgical procedures have a poor prognosis. Our experience of two patients, with aneurysmal dilatation of the ascending aorta is presented. The first patient presented with an aortic dissection extending from the ascending aorta to the common iliac arteries. The second patient presented with asymptomatic but progressive aneurysmal dilatation of the aortic root. Both patients underwent the Bentall procedure using a 25 mm St. Jude composite valved conduit. Despite increased vascular friability, both of these patients tolerated the operative procedure without complication and are doing well on early follow-up. This experience suggests that the Bentall procedure may be used to decrease the risks of dissection and rupture of the ascending aorta in patients with Ehlers-Danlos syndrome.

The social and emotional impact of cardiac transplantation.

To date, there has been limited systematic research in the area of the emotional impact of cardiac transplantation. Since September 1984, a prospective study addressing this issue has been in progress at St. Vincent's Hospital, Sydney, Australia. Initial results suggest that anxiety, associated with declining health and adjustment to the prospect of transplantation, was the major issue at pre-transplantation. Follow-up at the time of their first hospital discharge after transplantation and again at 3 months showed improvement in all psychological measures and did not identify any psychological morbidity.

Reproducibility of radionuclide left ventricular ejection fraction in patients awaiting cardiac transplantation.

Radionuclide-derived left ventricular ejection fraction (LVEF) is used to assess LV systolic function, to follow trends in the natural history of dilated cardiomyopathy, and to prioritize patients waiting for cardiac transplantation. Reproducibility of LVEF at extremely low levels has not, however, been reported. To assess the reproducibility of radionuclide LVEF at levels below 0.30 EF U, 17 highly symptomatic patients (NYHA Class III/IV) with dilated cardiomyopathy were studied on two occasions, 72 hours apart. Sequential scans were analyzed by two independent observers. Mean LVEF was 0.18 +/- 0.06 U (scan 1) and 0.17 +/- 0.06 U (scan 2). Interoperator reproducibility (SD) was 0.03 U (R = 0.76), interscan reproducibility (SD) was 0.03 U (R = 0.62), and overall reproducibility (SD) was 0.04 U (R = 0.50). The interobserver variation of 0.03 (actually 0.027) was just over one half that seen in normal volunteers (variation 0.05, n = 29) studied previously in this department. A change of greater than or equal to 0.08 U (2SD) in either direction is highly likely to represent a real change in LV function in those with LVEF less than or equal to 0.30 units, compared with the change of at least 0.10 units required in those with normal LV function. Lower interobserver and interscan reproducibility should be taken into account when interpreting sequential scans in patients with severe LV dysfunction.

Infected ventricular septal defect.

This paper reports a case of recurrent septic pulmonary emboli resulting from bacterial endocarditis on a ventricular septal defect. This was managed by the removal of vegetations, resection of the septal leaflet of the tricuspid valve, closure of the ventricular septal defect, and pulmonary embolectomy. The literature regarding the incidence and mortality of bacterial endocarditis on ventricular septal defects, and the management of the infected tricuspid valve, is reviewed. The patient remains well two and a half years after surgery.

Arterial counterpulsation in severe refractory heart failure complicating acute myocardial infarction.

The role of arterial counterpulsation was sought in 100 patients with severe refractory cardiac failure complicating myocardial infarction. Seventy-four were in shock and 26 were not. Average duration of counterpulsation was 7.0 days. Hospital survival was 34 per cent (25/74) in shock (predicted less than 10%) and 65 per cent in patients who were not in shock (predicted less than 50%). Survival at 4 years was 10 +/- 4 per cent in shock and 37 +/- 11 per cent in patients not in shock; functional status was class 1 or 2 in 5 of 9 patients in shock and in 8 of 12 survivors not in shock. Results were best when counterpulsation was started early after onset of symptoms, when ischaemic pain was still present, or when a mechanical defect was corrected surgically. Early coronary artery bypass surgery performed alone in 9 patients did not influence survival or functional status. Complications of counterpulsation occurred in 17 patients in shock and in 2 patients not in shock, all but 6 on the first day; none directly caused death. Counterpulsation is an effective and safe adjunct to medical treatment of complicated infarction provided the intervention is prompt.

Cardiac valve replacement (1963-1979).

A 15-year experience (from 1963-1978) in cardiac valve replacements with mechanical prosthetic valves (caged ball or tilting disc types) and with bioprostheses (porcine xenografts) is reported. The actuarial survival rates for patients who received the caged ball type prostheses (Starr-Edwards) were 42% and 36% respectively for mitral valve-replacements at 12 and 14 years. The actuarial survival rate for patients who received the tilting disc type prostheses (Björk-Shiley type and later the Lillehei-Kaster type) was 74% at six to seven years. The actuarial survival rate for patients who had aortic valve replacement with a caged ball valve was 43% at 14 years, and for those who had a tilting disc valve it was 80% at six to seven years. Multiple valve replacements were carried out with combinations of prostheses. The actuarial survival rate for patients was 65% for triple valves, and 57% for double valves at 13 years. Bioprostheses are now our first choice as cardiac valve replacements. In 121 implants performed since 1977, there have been two operative deaths, but no late deaths. Bioprostheses, although less thrombogenic than mechanical valve prostheses, are less durable and some risk of thromboembolism remains.

Post-infarction cardiac rupture.

Three allied conditions are described in this paper: (i) haemopericardium with cardiac rupture (5 cases); (ii) haemopericardium without rupture (2 cases); (iii) pseudoaneurysm (1 case). In the first 2 of these, the significant features were clinical deterioration with shock 3 or more days after infarction, recurrent cardiac pain, cardiac tamponade, and immediate or later ineffectiveness of counterpulsation. An additional feature in the second group was the development of haemopericardium after heparin therapy. In the third group, infarction followed by left ventricular failure and progressive cardiac enlargement was the significant feature. An apical systolic murmur was not present, as a false sac had not been formed. Ante-mortem diagnosis depends upon an appreciation of these features. Without it successful surgery is impossible. There were 4 survivors in this group of 8 patients.

Calcification of the mitral annulus.

Successful valve replacement has been achieved within the first three years in two patients who had extensive calcification of the mitral valve annulus. This condition, although commonly reported in pathology and autopsy studies, has been rare in our clinical experience. Surgical management does not appear to us to have been reported previously. It was regarded in our earlier experience as a deterrent to mitral valve surgery. Certain technical factors which contributed to success are emphasized in the two cases described in this report.