Bruno Reichart

Long-Term Survival in Patients With Repair of Tetralogy of Fallot: 36-Year Follow-Up of 490 Survivors of the First Year After Surgical Repair

OBJECTIVES We sought to analyze risk factors for long-term survival (up to 36 years) after surgical repair of tetralogy of Fallot (TOF). BACKGROUND Survival after repair is excellent, but data >20 years are rare. METHODS From 1958 to 1977, 658 patients underwent correction of TOF at our institution and were analyzed for survival. Of this patient group (age 12.2 +/- 8.6 years [mean +/- SD], range 2 to 67), 39.7% had a previous palliation. Operative (n = 139) and 1-year (n = 29) deaths were excluded for long-term calculations, resulting in a study group of 490 patients. RESULTS Actuarial 10-, 20-, 30- and 36-year survival rates were 97%, 94%, 89% and 85%, respectively. Mortality increased 25 years postoperatively from 0.24%/year to 0.94%/year (p = 0.003). The most common cause of death was sudden death (n = 13), followed by congestive heart failure (n = 6). Multivariate correlates of impaired long-term survival were date of operation (before 1970, p = 0.0104), preoperative polycythemia (p = 0.0487) and use of a right ventricular (RV) outflow patch (p = 0.0079). Postoperative systolic RV/left ventricular pressure ratio and age showed no influence. Patients without preoperative polycythemia and an RV outflow patch (n = 164) had a 36-year actuarial survival rate of 96% and normal life expectancy. CONCLUSIONS Cyanosis, operative experience of the surgeon and an RV outflow tract patch influence long-term outcome after repair of TOF in older children. Early repair by experienced surgeons to avoid polycythemia and excessive RV hypertrophy is supported by this study. However, mortality risk increases 25 years postoperatively, and thus heart monitoring should be intensified.

Simvastatin Reduces Graft Vessel Disease and Mortality After Heart Transplantation A Four-Year Randomized Trial

BACKGROUND Accelerated graft vessel disease (GVD) represents the most serious long-term complication of heart transplantation. A possible cause underlying this progressive coronary vascular disease is believed to be post-transplantation hypercholesterolemia. METHODS AND RESULTS In a 4-year prospective randomized study with heart transplant recipients, the efficacy of primary antihypercholesterolemic therapy with simvastatin was compared with that of general dietary therapy. The aim of the treatment was to maintain post-transplantation LDL-cholesterol levels at <120 mg/dL. Seventy-two heart transplant recipients receiving standard triple immunosuppression were randomly assigned to an active-treatment group (low-cholesterol diet and simvastatin, n=35) or a control group (general dietary measures, n=37). In the course of 4 years after transplantation, the simvastatin group had significantly lower LDL-cholesterol concentrations than the control group (mean+/-SD, 115+/-14 versus 156+/-17 mg/dL,P=.002), a significantly better long-term survival (88.6% versus 70.3%,P=.05), and a lower incidence of GVD in the coronary angiographic findings (16.6% versus 42.3%,P=.045). The incidence of graft rejections did not differ between the two groups, although there was a tendency toward a lower number of serious rejections in the simvastatin group (2.8% versus 13.5%, P=.1). Intracoronary ultrasound performed after 4 years in a subgroup of 27 patients (simvastatin, 10; control, 17) showed less intimal thickening in patients with LDL-cholesterol levels of <110 mg/dL (170+/-84 versus 370+/-171 microm, P=.04) and a lower intimal index (13.8+/-7.1% versus 27.9+/-12.1%,P=.04). CONCLUSIONS In comparison with dietary measures alone, the combination of a low-cholesterol diet and simvastatin after heart transplantation led to a significant reduction in cholesterol levels, a significantly higher long-term survival rate, and a lower incidence of GVD.

Shedding of the Endothelial Glycocalyx in Patients Undergoing Major Vascular Surgery With Global and Regional Ischemia

Background— The astonishing thickness of the endothelial glycocalyx, which rivals that of endothelial cells in the microvasculature, was disclosed in the last 15 years. As already demonstrated, this structure plays a key role in the regulation of inflammation and vascular permeability. Methods and Results— Two components of the glycocalyx, syndecan-1 and heparan sulfate, were measured in arterial blood of 18 patients undergoing surgery of the ascending aorta with cardiopulmonary bypass (n=12 with and n=6 without deep hypothermic circulatory arrest) and of 14 patients undergoing surgery for infrarenal aortic aneurysm. Basal values of syndecan-1 (1.2 &mgr;g/dL) and heparan sulfate (590 &mgr;g/dL) of patients were similar to those of control subjects. Anesthesia and initiation of surgery caused no changes. Global ischemia with circulatory arrest (n=12) was followed by transient 42- and 10-fold increases in syndecan-1 and heparan sulfate, respectively, during early reperfusion (0 to 15 minutes). After regional ischemia of heart and lungs (cardiopulmonary bypass; n=6), syndecan-1 increased 65-fold, and heparan sulfate increased 19-fold. Infrarenal ischemia was followed by 15- and 3-fold increases, respectively (n=14). The early postischemic rises were positively correlated (r=0.76, P<0.001). Plasma concentrations of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 did not change. Circulating polymorphonuclear granulocytes and the level of postischemic heparan sulfate corresponded negatively. Immunohistochemical imaging and immunoassay of isolated hearts (guinea pig) substantiated syndecan-1 and heparan sulfate as components of the endothelial glycocalyx released into the coronary venous effluent. Electron microscopy revealed shedding of the glycocalyx after ischemia/reperfusion. Conclusions— This study provides the first evidence in humans for shedding of the endothelial glycocalyx during ischemia/reperfusion procedures.

Continuous cardiac output by femoral arterial thermodilution calibrated pulse contour analysis: comparison with pulmonary arterial thermodilution.

OBJECTIVE To compare two thermodilution methods for the determination of cardiac output (CO)-thermodilution in the pulmonary artery (COpa) and thermodilution in the femoral artery (COa)-with each other and with CO determined by continuous pulse contour analysis (COpc) in terms of reproducibility, bias, and correlation among the different methods. Good agreement between the methods would indicate the potential of pulse contour analysis to monitor CO continuously and at reduced invasiveness. DESIGN Prospective criterion standard study. SETTING Cardiac surgical intensive care unit in a university hospital. PATIENTS Twenty-four postoperative cardiac surgery patients. INTERVENTIONS Without interfering with standard hospital cardiac recovery procedures, changes in CO as a result of the postsurgical course, administration of vasoactive substances, and/or fluid administration were recorded. CO was first recorded after a 1-hr stabilization period in the intensive care unit and hourly thereafter for 6 hrs, and by subsequent determinations at 9, 12, and 24 hrs. MEASUREMENTS AND MAIN RESULTS There were 216 simultaneous determinations of COpa, COa, and COpc. COpc was initially calibrated using COa, and no further recalibration of COpc was performed. COpa ranged from 3.0 to 11.8 L/min, and systemic vascular resistance ranged from 252 to 2434 dyne x sec/cm5. The mean difference (bias) +/-2 SD of differences (limits of agreement) was -0.29+/-1.31 L/min for COpa vs. COa, 0.07+/-1.4 L/min for COpc vs. COpa, and -0.22+/-1.58 L/min for COpc vs. COa. In all but four patients COpc correlated with COa after the initial calibration. Correlation and precision of COpc vs. COa was stable for 24 hrs. CONCLUSIONS Femoral artery pulse contour CO correlates well with both COpa and COa even during substantial variations in vascular tone and hemodynamics. Additionally, CO determined by arterial thermodilution correlates well with COpa. Thus, COa can be used to calibrate COpc.

Randomized Comparison of Percutaneous Coronary Intervention With Sirolimus-Eluting Stents Versus Coronary Artery Bypass Grafting in Unprotected Left Main Stem Stenosis

OBJECTIVES The purpose of this randomized study was to compare sirolimus-eluting stenting with coronary artery bypass grafting (CABG) for patients with unprotected left main (ULM) coronary artery disease. BACKGROUND CABG is considered the standard of care for treatment of ULM. Improvements in percutaneous coronary intervention (PCI) with use of drug-eluting stents might lead to similar results. The effectiveness of drug-eluting stenting versus surgery has not been established in a randomized trial. METHODS In this prospective, multicenter, randomized trial, 201 patients with ULM disease were randomly assigned to undergo sirolimus-eluting stenting (n = 100) or CABG using predominantly arterial grafts (n = 101). The primary clinical end point was noninferiority in freedom from major adverse cardiac events, such as cardiac death, myocardial infarction, and the need for target vessel revascularization within 12 months. RESULTS The combined primary end point was reached in 13.9% of patients after surgery, as opposed to 19.0% after PCI (p = 0.19 for noninferiority). The combined rates for death and myocardial infarction were comparable (surgery, 7.9% vs. stenting, 5.0%; noninferiority p < 0.001), but stenting was inferior to surgery for repeat revascularization (5.9% vs. 14.0%; noninferiority p = 0.35). Perioperative complications including 2 strokes were higher after surgery (4% vs. 30%; p < 0.001). Freedom from angina was similar between groups (p = 0.33). CONCLUSIONS In patients with ULM stenosis, PCI with sirolimus-eluting stents did not show noninferiority [corrected] to CABG at 12-month follow-up with respect to freedom from major adverse cardiac events, which is mainly influenced by repeated revascularization, whereas for hard endpoints, [corrected] PCI results are favorable. A longer follow-up is warranted. [corrected]

Hemodynamic and metabolic responses to hormonal therapy in brain-dead potential organ donors.

An evaluation of the beneficial effects of hormonal therapy, consisting of T3 2 micrograms, cortisol 100 mg, and insulin 20 units, administered at hourly intervals intravenously, was assessed in brain-dead patients referred for organ donation. Twenty-six conventionally treated donors (group A) showed a progressive hemodynamic deterioration requiring significant increments of inotropic support in order to maintain cardiovascular stability, necessitating a significant increase in bicarbonate requirements in order to maintain a normal acid-base balance. Of this group, 20% of the donors were considered unsuitable as cardiac donors due to progressive cardiovascular deterioration or sudden ventricular fibrillation. Hormonal therapy was administered to 21 donors (group B) resulting in a significant improvement of cardiovascular status, requiring less inotropic support and significantly less bicarbonate. A significant reduction of serum lactate-pyruvate followed the initiation of the hormonal therapy. In group B, organs from all donors (heart, heart and lungs, and kidneys) were suitable for transplantation, with excellent organ function following implantation of the graft.

Reliability of a new algorithm for continuous cardiac output determination by pulse-contour analysis during hemodynamic instability.

Objective The method of determining continuous cardiac output (CO) with beat-to-beat pulse-contour analysis calibrated by transthoracic thermodilution is gaining much wider clinical acceptance. However, some questions have been raised regarding the reliability of this method during periods of profound hemodynamic instability. We validated the original calculation of pulse-contour analysis and a new, improved algorithm against thermodilution-derived measurements of CO in patients with changes of CO >20%. Design Comparative study. Setting Cardiac surgical intensive care unit of a university hospital. Patients Twenty-four patients after cardiac surgery who experienced changes of CO >±20% during their postoperative course. Interventions CO was measured by transthoracic thermodilution and pulse-contour analysis (PiCCO, PULSION Medical Systems, Munich, Germany) at serial intervals every 60 mins during study periods of 8–44 hrs. During this time, no recalibration of the pulse-contour computer was performed. Measurements and Main Results A total of 517 simultaneous measurements of thermodilution CO and pulse-contour CO measured by the two different algorithms were compared by regression, structural regression, and Bland-Altman analyses. Mean change of CO was 40% ± 27% (range, 20% to 139%), range of systemic vascular resistance was 450–2360 dyne·sec/cm5. Correlation of the original pulse-contour algorithm to thermodilution CO was r = .76, with p = .027; bias was 0.08 L/min, with 1.8 L/min single sd. Correlation of the improved pulse-contour algorithm to thermodilution CO was r = .88, with p = .0001; bias was 0.2 L/min, with 1.2 L/min single sd. Mean CO by the new pulse-contour algorithm did not differ significantly from CO by thermodilution during the study period. The difference between the methods was not influenced by variations of heart rate or arterial pressure. Conclusions CO measurement by arterial pulse-contour analysis based on a new, improved algorithm is reliable, even in patients with profound changes of CO and during periods of hemodynamic instability.

Photopheresis for the Prevention of Rejection in Cardiac Transplantation

BACKGROUND Photopheresis is an immunoregulatory technique in which lymphocytes are reinfused after exposure to a photoactive compound (methoxsalen) and ultraviolet A light. We performed a preliminary study to assess the safety and efficacy of photopheresis in the prevention of acute rejection of cardiac allografts. METHODS A total of 60 consecutive eligible recipients of primary cardiac transplants were randomly assigned to standard triple-drug immunosuppressive therapy (cyclosporine, azathioprine, and prednisone) alone or in conjunction with photopheresis. The photopheresis group received a total of 24 photopheresis treatments, each pair of treatments given on two consecutive days, during the first six months after transplantation. The regimen for maintenance immunosuppression, the definition and treatment of rejection episodes, the use of prophylactic antibiotics, and the schedule for cardiac biopsies were standardized among all 12 study centers. All the cardiac-biopsy samples were graded in a blinded manner at a central pathology laboratory. Plasma from the subgroup of 34 patients (57 percent) who were enrolled at the nine U.S. centers was analyzed by polymerase-chain-reaction amplification for cytomegalovirus DNA. RESULTS After six months of follow-up, the mean (+/-SD) number of episodes of acute rejection per patient was 1.44+/-1.0 in the standard-therapy group, as compared with 0.91+/-1.0 in the photopheresis group (P=0.04). Significantly more patients in the photopheresis group had one rejection episode or none (27 of 33) than in the standard-therapy group (14 of 27), and significantly fewer patients in the photopheresis group had two or more rejection episodes (6 of 33) than in the standard-therapy group (13 of 27, P=0.02). There was no significant difference in the time to a first episode of rejection, the incidence of rejection associated with hemodynamic compromise, or survival at 6 and 12 months. Although there were no significant differences in the rates or types of infection, cytomegalovirus DNA was detected significantly less frequently in the photopheresis group than in the standard-therapy group (P=0.04). CONCLUSIONS In this pilot study, the addition of photopheresis to triple-drug immunosuppressive therapy significantly decreased the risk of cardiac rejection without increasing the incidence of infection.

Use of the voice-controlled and computer-assisted surgical system zeus for endoscopic coronary artery bypass grafting

OBJECTIVE With the aim of performing a completely endoscopic coronary bypass anastomosis, we have undertaken an experimental and clinical study using robotic instrumentation and voice-controlled camera guidance. METHODS The ZEUS Robotic Surgical System (Computer Motion Inc, Goleta, Calif) consists of three interactive robotic arms and a control unit, allowing the surgeon to move the instrument arms in a scaled down mode. The third arm (AESOP, Computer Motion) positions the endoscope via voice control. PHASE I In a phantom model, vascular grafts were anastomosed to the left anterior descending coronary artery (LAD) of 50 pig hearts with either 2- or 3-dimensional visualization. PHASE II In 6 dogs (FBI 20-25 kg) the left internal thoracic artery (LITA) was harvested endoscopically. Then the animals were placed on an endovascular cardiopulmonary bypass system (Port-Access, Heartport, Inc, Redwood City, Calif). Anastomosis of the LITA to the LAD was performed endoscopically with the telemetric ZEUS instruments. Flow rates through the LITA were measured by Doppler analysis. PHASE III Two patients were operated on with the ZEUS system. After endoscopic harvesting of the LITA and cardiopulmonary bypass with the Port-Access system, the bypass graft (LITA-LAD) was anastomosed endoscopically with the ZEUS system through three thoracic ports. RESULTS In the dry laboratory, the time range required for the robotically assisted coronary anastomosis was 35 to 60 minutes with 2-dimensional visualization and 16 to 32 minutes with 3-dimensional visualization. In the animal experiments, the median time for endoscopic harvesting of the LITA was 86 minutes (range 56-120 minutes) and for the anastomosis, 42 minutes (range 35-105 minutes); flow rates through the LITA ranged between 22 and 45 mL/min. In the clinical cases, preparation times for the LITA were 83 and 110 minutes, respectively, and anastomosis times, 42 and 40 minutes, respectively. Doppler flow rates measured 125 and 85 mL/min, respectively. Both patients had an uneventful follow-up angiogram and postoperative course. CONCLUSIONS With sophisticated robotic technology, a completely endoscopic anastomosis of the LITA to the LAD is possible, allowing technically precise operations within acceptable time limits.

Central venous pressure, pulmonary capillary wedge pressure and intrathoracic blood volumes as preload indicators in cardiac surgery patients

OBJECTIVE Monitoring of cardiac preload is mainly performed by measurement of central venous and pulmonary capillary wedge pressure in combination with assessment of cardiac output, applying the pulmonary arterial thermal dilution technique. However, the filling pressures are negatively influenced by mechanical ventilation and the pulmonary artery catheter is criticized because of its inherent risks. Measurement of right atria, right ventricular, global end diastolic and intrathoracic blood volume index by arterial thermal dye dilution utilizing the COLD-system may represent an alternative. METHODS In 30 CABG patients with an uncomplicated postoperative course the mentioned parameters were measured 1, 3, 6, 12 and 24 h postoperatively to prove their qualification as preload indicators: As patients received no inotropic support, changes of cardiac index and stroke volume index must correlate to changes of presumably preload indicating parameters. RESULTS When arterial and pulmonary arterial thermal dilution were compared, no differences were found; the correlation coefficient being 0.96, the bias 0.16 l/min per m2 (2.4%) and coefficients of variation did not exceed 7%. Changes of central venous pressure, capillary wedge pressure, right atrial end diastolic volume index and right ventricular end diastolic volume index did not correlate at all to changes of cardiac and stroke volume index (coefficients ranged from -0.01 to 0.28). In contrast, intrathoracic and global end diastolic blood volume indices with coefficients from 0.76 to 0.87, did show a good correlation to cardiac and stroke volume index. CONCLUSION Central venous pressure, capillary wedge pressure, right atrial and right ventricular end diastolic volumes are no suitable preload parameters in cardiac surgery intensive care, compared to intrathoracic and global end diastolic blood volumes. The latter show a higher clinical value and can be obtained by less invasive methods, as no pulmonary artery catheter is required.