Postinfarct refractory right ventricle: right ventricular exclusion. A possible option to mechanical cardiac support, in patients unsuitable for heart transplant.

BACKGROUND: Postbypass refractory right ventricle (RRV) may develop due to right ventricular (RV) ischemia or infarction. In cases with RV infarction, recovery is often prolonged and salvage rate is extremely poor. In this retrospective study, we have examined the role of right ventricular exclusion (RVE), as a possible option to conventional weaning or bridging to heart transplant (B-HTX), in patients who were unsuitable for heart transplant. METHODS: During last 5 years, cumulative incidence of postbypass refractory circulatory failure (RCF) in our adult patients was 0.39% (26/6542). This problem was caused by a RRV in 17 (65%) patients. After CABG, these patients developed a grossly distended and poorly contracting RV (RVEDV: 330-400 ml, RVEF: 0-10%), high central venous pressure (> or =18 mmHg) and an inadequate aortic pressure for weaning off cardiopulmonary bypass. Three patients, who were unacceptable for HTX under UNOS program (age >65 years), were weaned off bypass after RVE, and remaining patients with RVAD (n=3) or BiVAD support, depending upon their concomitant moderate or poor left ventricular performance. RESULTS: The significant predictors of RRV by univariate analysis were; 2nd or 3rd redo CABG for a recent myocardial infarction, and failed graft angioplasty. Hospital mortality (14-60 days) was 0/3, 3/3 and 3/11 for the patients weaned off with RVE, RVAD and BiVAD respectively. At 3 years, overall salvage rate was 9/17 (RVE: 3/3, BiVAD B-HTX 4/6 + 2 weaned with BiVAD support). CONCLUSION: Right ventricular exclusion is a possible option to conventional B-HTX with mechanical support, in patients who develop postinfarct RRV and are unsuitable for transplant.

Reoperative coronary artery bypass surgery: early and late results and management in 1300 patients.

In this retrospective series overall results after reoperative coronary artery bypass surgery and the subsequent management of recurrent ischemic heart disease in these patients were reviewed. Between September 1980 and September 1993, 17% (n = 1300) of our patients (Pts) undergoing myocardial revascularization (CABG) were reoperative. Of these, 75% were male and 17% were > or = 70 years. One or both internal thoracic arteries (ITA) were used in 25% Pts; a saphenous vein graft (SVG) was used sequentially in 67% or as a separate conduit in 8%. Hospital mortality was higher after redo CABG than after primary CABG (6.9% vs 2.1%, p < 0.0001) and also in Pts receiving SVG rather than IMA as a conduit (7% vs 3.8%, p < 0.001), and in Pts receiving retrograde coronary sinus cardioplegia (RCSC) (n = 504) as compared to those who received antigrade cardioplegia since 1989 (n = 334) (2.5 vs 5.4%, p < 0.05). Throughout the series, independent predictors of hospital mortality by multivariate analysis were: female gender, postoperative myocardial infarction, congestive cardiac failure and stroke. Actuarial survival at 10 years for the patients receiving ITA as a conduit was 86% and for the patients receiving SVG only 76% (p < 0.02); for patients > 70 years was 66% and for patients < 70 years 80% (p < 0.005). Pts with a LVEF < 20% had a poor survival after 2 years. At 10 years cardiac related event free survival after 1st reoperation was 53%. During 13 years 94 Pts underwent subsequent reoperations and 125 Pts underwent saphenous vein graft angioplasty (PTCA), for recurrent ischemic heart disease. Cardiac event free survival at 6 years was clearly superior after multiple reoperative surgery than after graft angioplasty (45% vs 35% p < 0.05). In conclusion, in this series, use of the ITA as a conduit and RCSC has significantly improved Pts survival after redo CABG. Survival and quality of life were further improved in patients requiring multiple reop CABG or graft PTCA.

Angioplasty versus coronary artery bypass in octogenarians.

We retrospectively analyzed early and late results for two treatment strategies of significant coronary artery disease in 310 octogenarians seen in the last 10 years. One hundred five patients 80 or more years of age had percutaneous transluminal coronary angioplasty (PTCA) and 205 had coronary artery bypass grafting (CABG). The PTCA group differed from the CABG group in having a greater proportion of women (71.4% versus 45.8%; p < 0.001); fewer patients with unstable angina (24.7% versus 33.6%; p < 0.04), acute myocardial infarction (11% versus 23%; p < 0.04), three-vessel coronary artery disease (20% versus 56%; p < 0.0001), and a left ventricular ejection fraction less than or equal to 0.30 (10% versus 21%; p < 0.008); and fewer vessels revascularized (1.2 +/- 0.6 versus 3.5 +/- 0.9; p < 0.0001). Hospital mortality was 8.57% after PTCA (9/14 failed PTCA) and 5.8% after CABG (4/14 emergent, 6/101 urgent, and 2/90 elective). Hospital stay was 7 +/- 0.9 days after PTCA and 14 +/- 1.5 days after CABG (p < 0.01). Independent predictors of hospital mortality obtained by multivariate analysis included failed PTCA and acute myocardial infarction (PTCA group), a left ventricular ejection fraction equal to or less than 0.30, and acute myocardial infarction and emergency CABG (CABG group). Survivors after both CABG and PTCA showed a significant improvement in their New York Heart Association class. Actuarial survival at 5 years after PTCA was 55% and after CABG it was 66% (p < 0.01). Cardiac event-free survival (deaths, myocardial infarction, PTCA, CABG) at 3 years was 61% after PTCA and 81% after CABG (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Surgical management in patients with coexistent coronary and cerebrovascular disease. Long-term results.

Between January 1980 and December 1992, 3% (210/6,862) of our patients undergoing myocardial revascularization (CABG) had high grade (> 80%) internal carotid stenosis (CS). One hundred seventy-five of these patients with complete follow up for a minimum of 18 months were studied. Bilateral internal CS was present in 60%, and 75% had other vascular lesions, mainly as peripheral vascular disease (PVD) of the lower limb (50.8%). All patients underwent CAE (carotid endarterectomy) followed by CABG under the same anesthesia. Peripheral vascular lesions, contralateral internal CS and recurrent (n = 43) and progressive vascular lesions (n = 50), were subsequently treated as staged procedures. Hospital mortality was 3.42%. By univariate analysis significant predictors of late mortality were congestive heart failure, COPD, PVD, postoperative myocardial infarction, postoperative stroke, and ischemic cardiomyopathy. Only the latter two were also significant by multivariate analysis. At 12 years, actuarial survival in the presence of these risk factors were 46%, 49%, 22%, 37%, 53%, and 27% respectively. All are significantly lower as compared with the corresponding subsets of patients with the risk factor absent. At 12 years, actuarial survival for the entire series was 65%. Cumulative incidence of postoperative strokes was higher in patients with bilateral internal CS than in patients with unilateral internal CS (p < 0.07) and in patients with neurologic symptoms than asymptomatic patients. At 12 years, actuarial freedom from all cardiac related events, postoperative stroke, and symptomatic PVD were 49%, 82%, and 76% respectively. After successful revascularization these patients should be carefully followed for recurrent and progressive vascular lesions.

Primary malignant pericardial mesothelioma: a case report and review.

Primary malignant pericardial mesothelioma is a rare tumor of unknown etiology. The prognosis is extremely poor due to generally late presentation, inability to completely eradicate it surgically and its poor response to radiotherapy or chemotherapy. An unusual case of pericardial mesothelioma which presented as constrictive pericarditis is described. A comprehensive review of the 140 cases reported in the literature so far is presented to assist the readers in the management and prognosis of this rare, pathological tumor.

Cardiac operations in patients with end-stage renal disease.

Factors influencing the survival of 35 consecutive patients in end-stage renal disease who required 40 open heart surgical procedures over the past 8 years were studied. The mean age in these patients was 57.7 +/- 3 years (range, 32 to 77 years); 74.3% of the patients were male; and the average duration of hemodialysis was 3.6 +/- 0.6 years. Twenty-nine myocardial procedures (20 of 29 for unstable angina), six valve replacements, and five combined procedures were performed. The actuarial survivals at 1 and 3 months, and at 1, 5, and 8 years were 90%, 85%, 76%, 55%, and 43%, respectively. Based on the results of univariate analysis, the most significant predictor of both early and late mortality was New York Heart Association (NYHA) class IV congestive heart failure. The 5-year survival in the patients 60 years and older was less favorable than that in patients younger than 60 years (45% versus 63%) (p < 0.05). The 5-year survival in the patients in NYHA class IV was only 27%, as compared to 63% in the patients in class II or III (p < 0.001). All survivors have remained free of angina and 19 of the 21 survivors showed an improvement in their NYHA class. Four patients under 40 years of age have subsequently been able to undergo renal transplantation. Overall, these results justify proceeding with an open heart surgical procedure in dialysis patients, when needed, but before the onset of congestive heart failure.

Management of coexistent carotid and coronary artery disease.

Simultaneous coronary artery bypass grafting (CABG) and carotid endarterectomy (CE) were done on 133 patients over an 8-year period. Twenty-seven patients (20%) had previous transient ischemic attacks (TIAs), 12 (9%) had previous strokes, and the remainder (71%) were asymptomatic. All asymptomatic patients had greater than 85% stenosis of the internal carotid artery demonstrated by noninvasive ultrasonography and four-vessel angiography. CE was performed prior to the sternotomy for coronary artery bypass, under the same anesthesia. Nineteen patients had bilateral carotid artery disease. Postoperatively, three patients (2.3%) suffered strokes, an additional three patients (2.3%) suffered transient upper extremity weakness, and one patient from each of these groups died. There were no postoperative strokes or TIAs in patients with bilateral carotid artery disease. Average length of hospital stay was 10 days. Our experience leads us to conclude that the morbidity and mortality of the simultaneous procedure are not affected by bilateral carotid artery disease. In patients with symptomatic coronary artery disease and symptomatic carotid artery disease or asymptomatic carotid artery disease with a high-grade stenosis, we think that simultaneous repair of both lesions should be done.

Prolonged survival of rat cardiac allografts by donor pretreatment with methotrexate. Enhancement by combined immunosuppressant treatment of the recipient.

Using an intraabdominal heterotopic cardiac transplant procedure, we determined that the Fischer 344 rat (donor)/Long Evans rat (recipient) combination provides a suitable model for studying acute rejection of cardiac allografts. Rejection time was 9.7 +/- 0.2 days. With this model we investigated the effect of donor pretreatment with methotrexate on allograft survival. Methotrexate injection at a single optimum dose of 100-200 mg/kg, i.p., resulted in a 55-60% increase in allograft survival with indefinite survival of some allografts. The optimum time for methotrexate administration was found to be 3-24 hr before transplant, indicating the clinical feasibility of this approach. Combining methotrexate with different recipient treatments (cyclosporine, methylprednisolone, or methylprednisolone plus azathioprine) resulted in significantly longer allograft survival than with any treatment alone. We have demonstrated a novel and clinically feasible approach to the treatment or prevention of acute allograft rejection. Such a treatment could allow reduction in the dose of immunosuppressant drugs to the recipient and thus lessen the toxicity of immunosuppressant therapy.

Improved survival of heterotopic cardiac allografts in rats with dietary n-3 polyunsaturated fatty acids.

A heterotopic cardiac transplant model, with male Fischer 344 rats as donors and Long Evans rats as recipients, was utilized to investigate the effect of dietary n-3 polyunsaturated fatty acids on acute rejection. Both donor and recipient rats were fed purified diets high in either n-3 polyunsaturated fatty acids (from concentrated n-3 ethyl esters [EE] or fish oil [FO]) or n-6 polyunsaturated fatty acids (from corn oil [CO]) for either 2-3 or 3-4 weeks before transplant. The recipient rats continued on their diets until rejection. The AIN-76A-based diets (with 30% of calories as fat) had adequate essential fatty acids and were balanced for sterols and antioxidants. Allograft survival was significantly increased by 45% when recipient rats were fed EE as compared to the control (CO diet fed to both donor and recipient), regardless of the diet fed to the donor. There was a slight but significant increase in allograft survival when only donor rats were fed the EE diet 2-3 weeks before transplant. With the FO diet (containing one third of the n-3 fatty acids in the EE diet), only the group fed FO to both donor and recipient (starting 2-3 weeks before transplant) showed a significant increase in allograft survival over the control. However, if the FO diets were fed for 3-4 weeks before transplant, increased survival was seen in groups fed FO to either the donor or recipient alone. In this case, allograft survival with FO feeding to both donor and recipient was not different from recipient treatment alone. In all the studies there was a significant and direct correlation between allograft survival and the donor heart phospholipid n-3/n-6 fatty acid ratio and the n-3 fatty acid content (at rejection). There was an indirect relationship with the n-6 fatty acid content. There was no detectable 20:3 (n-9) in the cardiac phospholipids, indicating the absence of essential fatty acid deficiency. Recipient diets were the strongest determinant of the fatty acid composition in the transplanted donor heart. The data indicate that providing dietary n-3 polyunsaturated fatty acids before and after cardiac transplant to recipient animals provides a significant protection against acute rejection.

Inhibition of platelet factor XIIIa-catalyzed reactions by calmodulin.

Calmodulin was found to exhibit an inhibitory effect on platelet factor XIIIa-catalyzed incorporation of pseudodonor amines into dimethylcasein, platelet actin and myosin. The inhibitory action of calmodulin on the calcium-dependent enzyme reactions was analogous to the effects of EGTA and parvalbumin on these reactions. The extent of inhibition of factor XIIIa activity was a function of calmodulin concentration when factor XIII and Ca2+ concentrations were held constant. These results indicate that calmodulin inhibits platelet factor XIIIa-catalyzed reactions by sequestering calcium.

Disulfide-linked and transglutaminase-catalyzed protein assemblies in platelets.

Energy depletion induces the formation of disulfide-linked and transglutaminase-catalyzed protein assemblies in platelets. The disulfide type polymers, formed following incubation at 37 degrees C in the absence of adenosine triphosphate (ATP)-generating precursors, are composed of cytoskeletal proteins and are associated with a decrease of reduced glutathione levels accompanying ATP depletion. The maintenance of ATP and reduced glutathione levels to, respectively, 34% and 47% of their original values is sufficient to prevent the formation of both polymer types. The transglutaminase-type cross-links are formed in the presence of calcium in either "energy-depleted" or thrombin stimulated platelets. 125I-surface-labeled membrane proteins, presumably transmembrane proteins, are incorporated into the transglutaminase-catalyzed cross-linked polymer of thrombin-stimulated platelets. Glycoproteins IIb and IIIa are not essential to the polymer formation, since thrombasthenic platelets treated with thrombin exhibit the same type of labeled polymer. The transglutaminase-catalyzed polymer formation following thrombin stimulation of platelets is inhibited by a calcium channel blocker, an intracellular calcium antagonist, as well as other inhibitors such as indomethacin, dibutyryl cyclic AMP, and prostaglandin E1. Although the evidence points to the formation of transglutaminase-catalyzed cross-linking in the cytoplasmic compartment, additional cross-linking of extruded components cannot be excluded.

Myocardial surgical revascularization after streptokinase treatment for acute myocardial infarction.

Eighty-six patients admitted with evolving myocardial infarction within 6 hours of symptom onset were treated with streptokinase. Thirty-nine received intracoronary streptokinase, and 47 received intravenous streptokinase. There were no streptokinase-related complications. Twenty-three patients treated with intracoronary streptokinase and 28 patients receiving intravenous streptokinase underwent coronary artery bypass grafting. On admission, 16 patients receiving intracoronary streptokinase had electrocardiographic evidence of anterolateral evolving myocardial infarction and seven had evidence of inferior evolving myocardial infarction. Time from first symptom to intracoronary streptokinase was 4.4 +/- 1.6 hours. In seven patients, intracoronary streptokinase failed to open the obstructed coronary. All developed severe left ventricular hypokinesia in the area supplied by that coronary artery. In spite of recanalization, nine of 14 patients developed severe hypokinesia in the supplied area, and one an apical aneurysm. Four patients developed mild to moderate hypokinesia, and one had no left ventricular damage. On admission, 14 patients receiving intravenous streptokinase had electrocardiographic evidence of anterolateral evolving myocardial infarction and four had evidence of inferior evolving myocardial infarction. Time from first symptom to intravenous streptokinase was 3.2 +/- 1.5 hours. In seven patients, intravenous streptokinase failed to open the coronary, and all developed severe hypokinesia of the supplied area, with formation of apical left ventricular aneurysm in three. In 21 patients, intravenous streptokinase opened the artery. Eighteen angiographies performed 9.6 +/- 7.9 days after therapy showed a normal left ventricle in eight patients, moderate hypokinesia in seven, and severe hypokinesia in three. Time from first symptom to therapy was shorter in the patients receiving intravenous therapy (p less than 0.01). Coronary artery bypass grafting and four resections after left ventricular aneurysm were performed without operative death. Two patients receiving intracoronary therapy died in the hospital, and one died 2 months later from arrhythmias. Freedom from angina and rehabilitation (New York Heart Association Class I) were achieved in 69.5% of patients receiving intracoronary streptokinase and in 75% of patients receiving intravenous streptokinase. Thus streptokinase-induced thrombolysis salvages myocardium, and the intravenous route seems as effective as the intracoronary. Advantages of the former are earlier administration that might increase myocardial salvage, no invasive procedure, and lesser cost.

Total lymphatic irradiation and bone marrow in human heart transplantation.

Six patients, aged 36 to 59 years, had heart transplants for terminal myocardial disease using total lymphatic irradiation (TLI) and donor bone marrow in addition to conventional therapy. All patients were poor candidates for transplantation because of marked pulmonary hypertension, unacceptable tissue matching, or age. Two patients are living and well more than four years after the transplants. Two patients died of infection at six and seven weeks with normal hearts. One patient, whose preoperative pulmonary hypertension was too great for an orthotopic heart transplant, died at 10 days after such a procedure. The other patient died of chronic rejection seven months postoperatively. Donor-specific tolerance developed in 2 patients. TLI and donor bone marrow can produce specific tolerance to donor antigens and allow easy control of rejection, but infection is still a major problem. We describe a new technique of administering TLI with early reduction of prednisone that may help this problem.

Paradoxical embolization with Ebstein's anomaly.

A 48-year-old woman with known Ebstein's anomaly had bilateral, lower-extremity arterial emboli after a total abdominal hysterectomy. She underwent embolectomy, placement of a Greenfield caval filter, subsequent tricuspid valve replacement, and closure of an atrial septal defect. Antemortem diagnosis of a paradoxical embolus is rare. To our knowledge, this is the first case associated with this congenital cardiac anomaly in a survivor.

Scintigraphic assessment of heterotopic cardiac transplants.

Patients receiving heterotopic ("piggyback") cardiac transplants, when the patient's own and transplanted donor hearts are connected in parallel, present special problems in determining their relative contributions to total cardiac function. Three patients who had transplants because of intractable heart failure were studied using first pass and gated equilibrium technetium-99m-labeled blood pool scintigraphy. In one patient, thallium-201 myocardial perfusion scans were obtained. These nuclear cardiology techniques provided anatomic and functional information noninvasively that proved helpful in patient management.

Improved myocardial preservation at 4 degrees C.

We tested the ability of various cardiac preservation techniques to preserve left ventricular function of isolated canine hearts using preservation temperatures of 4 degrees or 15 degrees C. The four techniques tested were: (1) topical hypothermia, and hypothermic arrest induced by (2) perfusion of 1 liter of a modified Collins solution, (3) perfusion of 1 liter of a modified extracellular solution (DKS), or (4) perfusion of 500 ml of blood cardioplegia. Following the cold ischemia period, the hearts were reperfused with blood in the working heart preparation and tested for their ability to recover left ventricular function. Hearts preserved 2 hours at 15 degrees C using hypothermia, modified Collins solution, or DKS solution achieved an average of 60, 73, and 95%, respectively, of baseline function. Hearts preserved 3 hours at 4 degrees C using topical hypothermia attained 70% of baseline function, while hearts stored 5 hours at 4 degrees C using modified Collins solution or DKS solution recovered 83 and 92%, respectively, of baseline function. Hearts preserved at 4 degrees C functioned at levels equal to or greater than that of hearts stored at 15 degrees C, even though the hearts preserved at 4 degrees C were stored for longer periods than those preserved at 15 degrees C. Hearts preserved with blood cardioplegia for 2 hours at either 4 degrees or 15 degrees C achieved functions statistically the same as baseline levels during the reperfusion period. These data show no advantage for preservation temperatures of 15 degrees C compared with 4 degrees C. Our data provide a firm experimental basis for the clinical use of myocardial preservation temperatures of 4 degrees C, especially when combined with cardioplegia.

Heart and kidney transplantation using total lymphoid irradiation and donor bone marrow in mongrel dogs.

Heart and kideny allografts showed markedly prolonged survival in unrelated mongrel dogs following total lymphoid irradiation (TLI) and donor bone marrow without any other immunosuppression. In every animal the heart survived longer than the kidney; genetic disparity was ruled out, since the heart and kidney from the same donor were placed into one recipient. Placing the kidney allograft in the abdomen with the bone marrow given intraperitoneally doubled kidney survival over placement in the neck, but heart survival was equally prolonged in the abdomen or neck. Splenectomy before TLI or after TLI, but just before transplantation, almost completely eliminated the prolonged survival of both heart and kidney allografts. Thus there is suggestive evidence from the work of Slavin and his colleagues and from our study that TLI plus bone marrow from the donor may be valuable for transplantation in man, particularly heart transplantation.

Left ventricular function after preserving the heart for 2 hours at 15 degrees C.

Hearts preserved for 2 hours at 15 degrees C were evaluated for maximum function with the use of an isolated working dog heart subjected to stress. We determined left ventricular function by controlling aortic flow resistance and flow into the left atrium. Groups studied were hypothermia alone (H), hypothermia with a modified extracellular solution (H + DKS), hypothermia with a modified Collins solution (H + C), six periods of 20 minutes of hypoxic hypothermia followed by 10 minutes of blood reperfusion (H20 + R10) and blood cardiplegia (BC). Hypothermia alone for 1 hour was also evaluated. Functions were studied for 2 1/2 hours following reperfusion by determining Starling's curves for each heart. Our data show that H alone gave adequate myocardial protection for only 1 hour but not for 2 hours. H20 + R10 was better than H, but function was depressed. Use of H + C provided protection equal to H20 + R10, but the hearts recovered function slowly. Only hearts preserved by H + DKS and BC for 2 hours had normal function. Hearts from all groups except H + DKS and BC became edematous. Excellent function was obtained with DKS or BC following 2 hours of ischemia at 15 degrees C. Initial clinical use of BC supported these laboratory findings.