Alternatives to heart transplantation. Symposium of the "Treatment of End-stage Heart and Lung Failure" working group on October 22, 2005 in Munich.

Heart transplantation is currently the treatment of first choice in patients with end-stage refractory heart failure. But already the demand for donor organs cannot be met, and patients face long waiting times for transplantation. In the future waiting times will become even longer as life expectancy increases and the number of heart-failure patients requiring transplantation grows. Consequently, in view of the poor prognosis of the disease in its advanced stages, alternatives to heart transplantation are increasingly gaining importance. In recent years new innovative treatment methods and techniques have been developed which have already proved clinically successful in patients with end-stage heart failure, especially as bridging measures. Some of these techniques appear suitable for long-term use and could therefore serve as an alternative to heart transplantation in some patients. Interesting new avenues of research may even lead to cardiac cell replacement therapies in the future. These approaches are currently undergoing initial clinical trials. This report presents surgical and cardiologic treatments for end-stage heart failure that have already been clinically investigated as well as techniques that are still in the preclinical stage and discusses their potential as alternatives to heart transplantation.

Outpatients on biventricular assist devices.

As waiting times for transplants have lengthened, long-term mechanical circulatory support (MCS) has become more common in patients who present with severe cardiogenic shock leading to multiorgan failure. With these patients, we used the biventricular assist device (BVAD, Berlin Heart). In this report, we will describe our 4 years of experience with 11 patients on a BVAD who were discharged home while awaiting transplantation. The 11 patients underwent BVAD implantation from 1997 to 2000. These were 2 women and 9 men. The mean support time was 382 days (range: 156 - 567). The indication for BVAD was cardiomyopathy--six dilated, one restrictive and four ischemic. These patients were monitored for infections, thromboembolic events, bleeding complications, and psychological effects during the time they spent at home. Our experience shows that all of the patients could leave hospital following sufficient training for dressings and anticoagulation after recovering completely from secondary organ dysfunction. The mean time period the patients spent at home was 48 days (range: 3 - 182) days. Seven patients (63 %) had to be readmitted to the hospital--due to transitory ischemic attacks in two cases, hemorrhoidal bleeding in one and wound infections in four cases. One patient died of a traumatic accident during sexual activity. The use of a BVAD is feasible for outpatient use as a bridge to transplantation. It ensures the survival of the patient, enables recovery from multiorgan failure and offers an acceptable quality of life.

Increased coagulation and bradykinin-release in shed pleural blood during cardiac surgery.

Retransfusion of shed pleural blood is generally believed to contribute to a decrease of intraoperative blood requirements, however, hemodynamic or hemostatic side effects are nevertheless still controversial. Some 13 patients (age: 58 +/- 11) undergoing CPB surgery including the use of the internal mammaria artery (IMA) were investigated. For IMA preparation, pleura of the left hemithorax was opened, allowing blood to accumulate within the pleural cavity. Some 472 +/- 258 ml blood volumes were retransfused after 79 +/- 11 min clamp time. After 50 +/- 15 s, mean arterial blood pressure (AP) dropped from 68 +/- 15 to 36 +/- 8 mm Hg, and the calculated systemic vascular resistance (SVR) decreased from 1124 +/- 263 to 596 +/- 153 dyn s(-1) cm5 (p < 0.01). Bradykinin levels in the retransfused shed blood showed significantly higher values (205 +/- 88 fmol/ml) compared to the systemic blood (24 +/- 19 fmol/ml). Thrombin-antithrombin-III complexes were strongly elevated in the shed pleural blood, and after retransfusion the systemic blood values increased significantly. After retransfusion of shed pleural blood during CPB an acute drop in AP and SVR occurred, probably caused by high bradykinin concentrations. We therefore recommend that the accumulation of shed blood is avoided by continuous retransfusion as is now the standard procedure in our University hospital.

Aprotinin in fibrin tissue adhesives induces specific antibody response and increases antibody response of high-dose intravenous application.

BACKGROUND: In cardiac operations, aprotinin therapy is used either locally as a component of commercially available fibrin tissue adhesives, intravenously, or combined. Our aim was to examine the formation of aprotinin-specific antibodies with regard to the application mode. METHODS: Sera of 150 patients who had undergone cardiac operations and were receiving aprotinin therapy for the first time were sampled before the operation and at medians of 3.5 and 13.3 months after the operation. Aprotinin-specific IgG including all subgroups and aprotinin-specific IgE were analyzed. Aprotinin was given locally (as contained in fibrin sealant; n = 45; median dose, 6000 KIU), intravenously (n = 46; 2.000 x 10(6) KIU), and combined (n = 59; 2.012 x 10(6) KIU). RESULTS: At 3.5 months, the prevalence of aprotinin-specific IgG antibodies was 33% (15/45 patients) after local, 28% (13/46 patients) after intravenous, and 69% (41/59 patients) after combined exposure (P =.0001). At 13.3 months, the prevalence of aprotinin-specific IgG antibodies was 10% (4/41 patients) after local, 31% (13/42 patients) after intravenous, and 49% (28/57 patients) after combined exposure. Total aprotinin dose was similar in patients who were antibody positive and negative. Before the operation, no aprotinin-specific antibodies were detected. Aprotinin-specific IgE were not found after the operation. CONCLUSION: Local aprotinin contact induces a specific immune response and reinforces that of intravenous exposure. The antibody spectrum is identical to the immune response induced by intravenous exposure. Any exposure should be documented. For use in cardiac operations as a hemostyptic, the necessity itself and alternatives for aprotinin as a stabilizing agent merit consideration.

Transmyocardial laser revascularization in the acute ischaemic heart: no improvement of acute myocardial perfusion or prevention of myocardial infarction.

OBJECTIVE: Transmyocardial laser revascularization (TMLR) has been used to provide enhanced myocardial perfusion in patients not suitable for coronary revascularization or angioplasty. This study investigates the acute changes in myocardial perfusion after TMLR with a Holmium:Yttrium-Aluminium-Garnet (YAG) laser with a thermal imaging camera in a model of acute ischaemia, and confirms its midterm effects by post-mortem investigation of magnetic resonance imaging and histopathological examination. METHODS: Acute myocardial ischaemia was induced by occlusion of the dominant diagonal branch in ten sheep. Perfusion measurements were undertaken first in the unaffected myocardium, then after temporary occlusion of the coronary to obtain a control measurement for ischaemic myocardium. Myocardial perfusion was then evaluated during reperfusion after release of coronary occlusion. Then the coronary was permanently occluded and 20.5+/-2 channels were drilled with the Holmium:YAG laser and perfusion was measured again. The other four sheep served as control with untreated ischaemia. All animals were sacrificed after 28 days following administration of gadolinium i.v. to serve as contrast medium for magnetic resonance tomography. The hearts were subjected to magnetic resonance tomography and histopathological examination. RESULTS: Intraoperative perfusion measurements revealed a decreased perfusion after temporary occlusion and an increased perfusion in reperfused myocardium. After TMLR, no improvement of myocardial perfusion above the ischaemic level could be shown. Magnetic resonance images could neither confirm patent laser channels nor viable myocardium within ischaemic areas. On histology no patent endocardial laser channel could be detected. The transmural features were myocardial infarct with scar tissue. CONCLUSIONS: In the presented sheep model with acute ischaemia, TMLR with a Holmium:YAG laser did not provide acute improvement of myocardial perfusion as assessed by a thermal imaging camera. This would suggest no direct contribution of newly created laser channels to myocardial perfusion. As chronic effects are concerned, no perfused laser channels could be identified by later magnetic resonance imaging or histology.

MR angiography and flow quantification of the internal mammary artery graft after minimally invasive direct coronary artery bypass.

OBJECTIVE: Six patients who had undergone minimally invasive direct coronary artery bypass surgery were examined to evaluate an MR imaging protocol that provided information about cardiac function, bypass graft patency, and flow characteristics with a single examination. CONCLUSION: Preliminary results suggest that our imaging protocol allows accurate follow-up of patients after minimally invasive direct coronary artery bypass surgery. Bypass graft patency was correctly determined in all patients. In four patients, anastomoses were visualized by MR angiography, and flow measurements revealed a volume range of 28-84 ml/min (native and grafted internal mammary arteries) and a trend for the flow values of bypass grafts to be lower than those of native vessels. Interobserver reproducibility was good (r = .99; slope, .98).

Left ventricular geometry and cardiac function during minimally invasive coronary artery bypass grafting.

BACKGROUND: This investigation was designed to study the changes in function and geometry of the left ventricle during two critical steps of minimally invasive direct coronary artery bypass procedures: placement of an epicardial stabilizer and occlusion of the left anterior descending coronary artery. METHODS: Between February 1997 and January 1998, 28 patients underwent bypass grafting with the left internal thoracic artery to the left anterior descending coronary artery (minimally invasive direct coronary artery bypass technique). Transesophageal echocardiography was used for determination of fractional area change and to assess left ventricular (LV) diameters in two dimensions and at the apex. RESULTS: Placement of the epicardial stabilizer resulted in a small decrease in LV end-systolic and end-diastolic dimensions; cardiac function remained unchanged. Subsequent occlusion of the left anterior descending coronary artery caused a moderate decline in cardiac index and fractional area change, an increase in LV diameters, and the development of hypokinetic segments within the LV myocardium. CONCLUSIONS: The use of an epicardial stabilizer provides a safe and effective means to stabilize the operative field during minimally invasive direct coronary artery bypass procedures. Monitoring of LV function by transesophageal echocardiography enhances the safety of such procedures and is highly recommended.

In vivo morphology of woven, collagen-sealed Dacron prostheses in the thoracic aorta.

BACKGROUND: Long-term changes in knitted Dacron grafts inserted into the infrarenal aorta have been addressed by a number of studies indicating their potential for postoperative dilatation. In contrast, the behavior of woven, collagen-presealed, double-velour Dacron grafts used to replace the thoracic aorta is not known. METHODS: Forty-five patients were examined at a mean of 32.4 +/- 14.8 months after insertion of woven, collagen-coated, Dacron double-velour prostheses (Meadox woven with Hemashield, Meadox, Oakland, NJ) in the thoracic position under highly standardized conditions using spiral computed tomography. RESULTS: Compared with a manufactured diameter of 26 mm, all grafts showed an increase of 1 to 5 mm (mean, 3.0 +/- 1.2 mm [11.6% +/- 4.4%]; p < 0.0001) with greater enlargement of the ascending than of the descending aortic portions (p = not significant). A further statistically significant progressive dilatation failed to occur. Degenerative changes, including false aneurysm formation, could be excluded. CONCLUSIONS: Woven, collagen-coated Dacron prostheses are considered a safe replacement material for the thoracic aorta.

Surgical management of persistent mediastinitis after coronary bypass grafting.

Persistent mediastinitis despite primary revision, closed irrigation therapy, and additional secondary omental plasty is a life threatening situation in cardiac surgery. We managed this rare complication in one instance by sternectomy and hemirectus plasty as well as bilateral pectoralis plasty.

Anaphylactic shock after aprotinin reexposure: time course of aprotinin-specific antibodies.

We report a case of severe anaphylactic shock during a cardiac operation that occurred as a consequence of aprotinin readministration in the presence of preformed aprotinin-specific antibodies. Both immunoglobulin G (3 hours) and immunoglobulin E (5 minutes) antibody levels dropped early after the clinical event. Despite their possibly limited clinical significance, we still recommend the conductance of specific antibody screening tests before readministration of aprotinin.

Graft coronary vasculopathy in cardiac transplantation--evaluation of risk factors by multivariate analysis.

The development of coronary vasculopathy is the main determinant of long-term survival in cardiac transplantation. The identification of risk factors, therefore, seems necessary in order to identify possible treatment strategies. Ninety-five out of 397 patients, undergoing orthotopic cardiac transplantation from 10/1985 to 10/1992 were evaluated retrospectively on the basis of perioperative and postoperative variables including age, sex, diagnosis, previous operations, renal function, cholesterol levels, dosage of immunosuppressive drugs (cyclosporin A, azathioprine, steroids), incidence of rejection, treatment with calcium channel blockers at 3, 6, 12, and 18 months postoperatively. Coronary vasculopathy was assessed by annual angiography at 1 and 2 years postoperatively. After univariate analysis, data were evaluated by stepwise multiple logistic regression analysis. Coronary vasculopathy was assessed in 15 patients at 1 (16%), and in 23 patients (24%) at 2, years. On multivariate analysis, previous operations and the incidence of rejections were identified as significant risk factors (P < 0.05), whereas the underlying diagnosis had borderline significance (P = 0.058) for the development of graft coronary vasculopathy. In contrast, all other variables were not significant in our subset of patients investigated. We therefore conclude that the development of coronary vasculopathy in cardiac transplant patients mainly depends on the rejection process itself, aside from patient-dependent factors. Therapeutic measures, such as the administration of calcium channel blockers and regulation of lipid disorders, may therefore only reduce the progress of native atherosclerotic disease in the posttransplant setting.

Valve reconstruction or replacement for long-term biopsy-induced tricuspid regurgitation following heart transplantation.

Tricuspid regurgitation following heart transplantation can become a severe problem in a subset of patients, where medical therapy fails. Operative findings are described and results of subsequent results with surgical intervention including repair and replacement are analysed. Although follow-up is short, tricuspid replacement seems superior to reconstruction following heart transplantation. Best results are obtained, if replacement is performed, before right ventricular function deteriorates.

Use of the "elephant trunk technique" in aortic surgery.

BACKGROUND: In aortic replacement, the "elephant trunk technique" uses surplus intravascular graft length to facilitate subsequent operations on the downstream aorta. This study investigates the experience with the technique since its conception by our group. METHODS: Between 1982 and 1994, 80 elephant trunks were implanted in 72 patients. In 40 cases the primary position was in the proximal descending thoracic aorta, extending an aortic arch graft. In 32 instances the elephant trunk was placed in the distal descending thoracic aorta, extending descending aortic replacement. Aortic pathology comprised aneurysms in 22 cases, chronic dissection in 47, and acute dissection in 3. Fourteen patients had Marfan's syndrome. RESULTS: There was a total of 10 early deaths, 7 of which occurred during the early experience. Subsequent downstream aortic operation was undertaken in 24 patients after a mean interval of 14 months, replacing the descending thoracic aorta in 17 cases and the thoracoabdominal portion in 7 cases. Six patients underwent third-stage procedures. Several technical modifications were developed, helping to ease placement and unfolding of the trunk. CONCLUSIONS: The elephant trunk technique greatly facilitates and at the same time reduces the risk of multiple-stage aortic replacement.

Preventive treatment of coronary vasculopathy in heart transplantation by inhibition of smooth muscle cell proliferation with angiopeptin.

BACKGROUND: The underlying mechanism of accelerated coronary vasculopathy in cardiac allografts still remains unclear. Our hypothesis was that inhibition of smooth muscle cell proliferation with the somatostatine analogue Angiopeptin may reduce vasculopathy. METHODS: Fifty-four patients received Angiopeptin injections (1500 micrograms x three times daily subcutaneously) for 21 days after the operation and three additional injections with every rejection treatment. Angiography was performed yearly, and data were compared with a matched historic control group. RESULTS: Actuarial survival was 85% at 1 year and 80% at 2 years, comparable with our results in general (80%/77%). Forty-six long-term survivors could be followed by coronary angiography. At 1 year, vasculopathy was assessed in nine patients (17%). Of the 18 patients investigated at 2 years thus far, an additional three patients were found to have vasculopathy. In the control group vasculopathy was comparable, being 13% after 1 year and 20% after 2 years. A significantly lower incidence of rejections and lower creatinine values were found in the study group within the entire observation period (p < 0.05). CONCLUSIONS: We conclude that Angiopeptin treatment appears to be safe without significant side effects; it may reduce the number of acute rejections, at least during the first year after heart transplantation. However, the results of the 2-year follow-up in the remaining patients would have to be included in assessing the effect of Angiopeptin. Long-term follow-up will be necessary to decide whether Angiopeptin will be helpful in reducing the incidence of transplant vasculopathy.

Retransplantation of the lung. A single center experience.

While lung retransplantation remains the only therapeutic option in early or late graft failure, its value is viewed controversially. Of 134 patients undergoing pulmonary transplantation in our institution, 13 patients underwent 14 redos following heart-lung transplantation (n = 3), bilateral lung transplantation (n = 5), and unilateral lung transplantation (n = 5). Indications for retransplantation were acute graft failure (n = 2), persistent graft dysfunction (n = 3), airway complications (n = 2), and chronic graft failure (n = 7). Prior to retransplantation, six patients had been in stable respiratory failure, the remaining eight patients were on mechanical ventilation or extracorporeal membrane oxygenation (n = 2). Four patients died, 19, 43, 142, and 683 days following retransplantation due to pneumonia (n = 2), early onset of obliterative bronchiolitis (n = 1), and pulmonary embolism (n = 1). There was no correlation between mortality and intubation prior to re-operating, timing of operation, donor cytomegalovirus (CMV) status, or type of operation. Postoperative need for intensive care treatment was prolonged in patients undergoing acute retransplantation (P < 0.05). Actuarial 1- and 2-year survival rates were calculated at 77 and 64%. This was slightly lower than in the overall population following primary isolated lung transplantation (83 and 80%). Actuarial freedom from obliterative bronchiolitis (stage 3) at 1 and 2 years was calculated at 88 and 27% (primary grafts: 88% vs 72%; P < 0.05). Retransplantation is a realistic option in early and late graft failure after lung transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Malperfusion of the thoracoabdominal vasculature in aortic dissection.

Ischemic damage to vital organs supplied by the thoracoabdominal aorta greatly increases the overall risk of aortic dissection. Of 320 patients operated upon for aortic dissection since 1985, 33 (10.3%) underwent operations directed at the relief of malperfusion (15/158 acute type A; 9/18 acute type B; 4/78 chronic type A; 5/66 chronic type B). Organs affected were the kidneys in 32; the bowel in 20; and the spinal cord in 1, while critical lower extremity ischemia was present in 11 patients. In total, 64 vascular areas were affected. Fenestration of the dissecting membrane with or without infrarenal grafting was the procedure performed most frequently in 25, followed by replacement of the descending or thoracoabdominal aorta in 6, and bypass grafting or direct revascularization of individual side branches in 6. Six other operations targeted at the affected organs were done. Twenty-four patients underwent one-stage operation for malperfusion; in 11, early reoperation after primary aortic repair was necessary, while 2 patients were operated electively. Ten of 33 patients died in hospital, 7 of malperfusion-induced complications. Of three late deaths, one was related to sequelae of malperfusion. We conclude that immediate diagnosis and prompt relief of malperfusion offer the best prospects for patient survival. Membrane fenestration appears to be the method of choice for treating malperfusion in most patients, and must be directed to the level of aortic and/or side branch obstruction.

Tactics and techniques of aortic arch replacement.

Operations on the nondissected and dissected aortic arch still pose challenges in terms of the need for and extent of aortic replacement. Our approaches to these lesions are described against the background of 204 operations (58 aneurysms, 54 chronic dissections, and 92 acute dissections), in terms of cerebral protection, procedural choices, and operative technique. Arch anastomoses sparing the supraaortic vessels had shorter periods of circulatory arrest (17.2 min) when compared to tubular arch replacement, with insertion of some or all of these vessels (33.7 min). Early death rates due to cerebral complications were lowest in acute dissections (3/14 fatalities, with two patients showing preoperative cerebral compromise). Based on our experience, we recommend doing subtotal or total arch replacement in aneurysms regardless of cause. Radical arch surgery should be avoided in acute dissections whenever feasible. Instead, the arch should be explored and a blood-tight distal anastomosis made, going beyond any entry tears encountered in that aortic portion.

Risk of replacement of descending aorta with a standardized left heart bypass technique.

Replacement of the descending aorta for aneurysms (51%) and dissection (49%) was performed in 132 patients with a highly standardized left heart vortex-pump bypass. No adjuncts other than staged aortic clamping and intercostal artery reconnection were used to reduce spinal cord injury in extensive involvement. Four patients (3%) died early, two of cardiac cause, and nine (7%) died late. Complications of vital organ function occurred in eight patients, two having reversible renal failure and six spinal cord injury that was permanent in three (2.3%). Cord injury occurred only in replacement beyond thoracic segment 8 and could not be completely avoided despite distal intercostal artery reconnection in two cases; in the other four cases such vessels either did not appear worth reconnecting or were sacrificed in emergency operations. We conclude that left heart bypass effectively unloads the proximal circulation during aortic occlusion while maintaining adequate perfusion of distal vital organs as evidenced by low rates of early mortality and renal failure. The remaining risk of spinal cord damage may be lowered by more aggressive reconnection of all distal intercostal arteries and by extending the permissible cord ischemic period by means of hypothermia.