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Biomedical subjects

Roland Hetzer

Publications and source records attributed to Roland Hetzer.

At least 109 records · Page 6Linked to original sources

Genome-wide array analysis of normal and malformed human hearts.

BACKGROUND: We present the first genome-wide cDNA array analysis of human congenitally malformed hearts and attempted to partially elucidate these complex phenotypes. Most congenital heart defects, which account for the largest number of birth defects in humans, represent complex genetic disorders. As a consequence of the malformation, abnormal hemodynamic features occur and cause an adaptation process of the heart. METHODS AND RESULTS: The statistical analysis of our data suggests distinct gene expression profiles associated with tetralogy of Fallot, ventricular septal defect, and right ventricular hypertrophy. Applying correspondence analysis, we could associate specific gene functions to specific phenotypes. Furthermore, our study design allows the suggestion that alterations associated with primary genetic abnormalities can be distinguished from those associated with the adaptive response of the heart to the malformation (right ventricular pressure overload hypertrophy). We provide evidence for the molecular transition of the hypertrophic right ventricle to normal left ventricular characteristics. Furthermore, we present data on chamber-specific gene expression. CONCLUSIONS: Our findings propose that array analysis of malformed human hearts opens a new window to understand the complex genetic network of cardiac development and adaptation. For detailed access, see the online-only Data Supplement.

Adaptation, Physiological↗

Uric acid and survival in chronic heart failure: validation and application in metabolic, functional, and hemodynamic staging.

BACKGROUND: Serum uric acid (UA) could be a valid prognostic marker and useful for metabolic, hemodynamic, and functional (MFH) staging in chronic heart failure (CHF). METHODS AND RESULTS: For the derivation study, 112 patients with CHF (age 59+/-12 years, peak oxygen consumption [Vo2] 17+/-7 mL/kg per minute) were recruited. In separate studies, we validated the prognostic value of UA (n=182) and investigated the relationship between MFH score and the decision to list patients for heart transplantation (n=120). In the derivation study, the best mortality predicting UA cutoff (at 12 months) was 565 micromol/L (9.50 mg/dL) (independently of age, peak Vo2, left ventricular ejection fraction, diuretic dose, sodium, creatinine, and urea; P<0.0001). In the validation study, UA >or=565 micromol/L predicted mortality (hazard ratio, 7.14; P<0.0001). In 16 patients (from both studies) with UA >or=565 micromol/L, left ventricular ejection fraction <or=25% and peak Vo2 <or=14 mL/kg per min (MFH score 3), 12-month survival was lowest (31%) compared with patients with 2 (64%), 1 (77%), or no (98%, P<0.0001) risk factor. In an independent study, 51% of patients with MFH score 2 and 81% of patients with MFH score 3 were listed for transplantation. The positive predictive value of not being listed for heart transplantation with an MFH score of 0 or 1 was 100%. CONCLUSIONS: High serum UA levels are a strong, independent marker of impaired prognosis in patients with moderate to severe CHF. The relationship between serum UA and survival in CHF is graded. MFH staging of patients with CHF is feasible.

Biomarkers↗

Standardized immune monitoring for the prediction of infections after cardiopulmonary bypass surgery in risk patients.

BACKGROUND: Infections are the most common cause of late complications in cardiopulmonary bypass (CPB) surgery patients, and are difficult to predict. Here we studied the diagnostic value of a standardized immune monitoring program based on recent advances in flow cytometry (exact quantification of surface-marker expression) and cytokine determination (semiautomatic systems). METHODS: CPB patients (56) at risk for complications (age >70 years and/or preoperative left-ventricular ejection fraction < 25 %) were classified into three groups: without (33), with suspected (14), and with confirmed (9) infection. Applying the Quantibrite trade mark -system, we daily quantified the expression of CD11b, CD64, CD71, CD86, and HLA-DR on monocytes/granulocytes. Furthermore, the ex vivo secretion of tumor necrosis factor (TNF)-alpha as well as the plasma interleukin (IL)-10 levels were determined by a semiautomatic system. Ex vivo elastase release was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: All patients showed signs of granulocyte activation and monocyte deactivation. Monocytic HLA-DR and plasma IL-10 were the best markers to discriminate patients with infection from those without as early as day 1. Using a cutoff of 5792 HLA-DR molecules per cell, both sensitivity and negative predictive value for patients who developed microbiologically confirmed infection was 1.0, and the area under the curve (AUC) was 0.85. CONCLUSIONS: Our data suggest that a standardized immune monitoring at day 1 might be useful for early discrimination of patients at elevated risk for infections.

Adult↗

Impact of body mass index on outcome in patients after coronary artery bypass grafting with and without valve surgery.

BACKGROUND: Among other preoperative parameters, extremely low or extremely high body mass index (BMI) has been discussed as a substantial risk factor for postoperative complications after cardiac surgery. However, the exact relationship between BMI and postoperative risk has not yet been defined. METHODS: We retrospectively investigated consecutive patients (n=22666) who underwent coronary artery bypass grafting with or without concomitant valve surgery between 1990 and 2001 in our institution. A number of preoperative and intraoperative variables and BMI (as a quadratic term) were used in a logistic regression model as covariates. Further, the patients were divided into 20 groups each with an increase in BMI of 1kg/m(2)(BMI as a categorical variable). The calculations of odds ratios (ORs) for re-intubation, infection, re-exploration, prolonged stay (>1 day) on the intensive care unit (ICU) and 30-day mortality were adjusted for age, gender and type of surgery. RESULTS: In the multivariate analysis only age (OR between 1.01 and 1.038, P<0.01), additional aortic valve (OR between 1.335 and 2.977, P<0.01) or mitral valve surgery (OR between 2.123 and 3.301, P<0.01) showed significant impact on all five end-points. Patients with BMI between 25 and 35kg/m(2)were not at elevated risk for any of the investigated end-points, except for infection. Patients with BMI between 21 and 27kg/m(2)were not at elevated risk for infection. The ORs for postoperative complications were significantly higher in underweight patients compared with obese or severely obese patients, except those for infection. Further, the underweight patients presented significantly more comorbidity. CONCLUSION: Patients with low BMI are at higher risk after cardiac surgery than obese or severely obese patients. We hypothesize that a preoperative focus on avoiding and/or reversing cachexia may be more efficacious than reducing obesity in reducing the overall risk associated with heart surgery.

Body Mass Index↗

Dislocated wrap after previous reduction aortoplasty causes erosion of the ascending aorta.

We report a patient with bicuspid aortic valve and dilatation of the ascending aorta who had previous aortic valve replacement and reduction aortoplasty with wrapping. After 4 years, reoperation because of coronary artery disease and paravalvular leakage revealed an erosion of the aortic wall due to dislocation of the wrap. This complication confirms the need for secure anchoring and good fitting of the Dacron wrap to avoid alterations of the underlying aortic wall.

Aorta↗

Stentless aortic valves as an alternative to homografts for valve replacement in active infective endocarditis complicated by ring abscess.

BACKGROUND: The valve substitute of choice in active infective aortic valve endocarditis complicated by annulus abscess in our institution is the cryopreserved homograft. To avoid implantation of any prosthetic material, the Shelhigh No-React stentless valves and conduits may be considered an alternative when no suitable homograft is available. METHODS: Between March 1986 and January 2001, 452 homografts were implanted in the aortic position. From January 2000 to August 2001, 75 Shelhigh No-React prostheses were implanted at our institution. In 25 consecutive patients (study group) with aortic annulus abscess, urgent aortic valve replacement with the Shelhigh SuperStentless and Stentless Aortic Valve Conduit was undertaken. Patients (16 male, 9 female; age, 49 +/- 19 years) were studied with follow-up until March 2002. The control group comprised 68 consecutive historical patients (46 male, 22 female; age, 53 +/- 14.4 years) with similar disease treated between January 1997 and December 1999 in whom an aortic homograft was implanted. This group was also followed up until March 2002. Demographic data and preoperative characteristics of the patients were without significant differences. Patients were studied by echocardiography. RESULTS: Sixty-day mortality was 16% (11 patients) in the control group compared with 12% (3 patients) in the study group. Recurrent infection occurred in 4% in both groups. The instantaneous and mean Doppler gradients yielded no significant differences (19.4 +/- 10.4 mm Hg and 11.8 +/- 5.7 mm Hg versus 18.2 +/- 8.7 mm Hg and 10.9 +/- 5.3 mm Hg, respectively). The mean effective orifice area calculated from Doppler flow velocity for the stentless valve was 2.3 +/- 0.6 cm2. Preoperative evaluation of left ventricular dimensions and global left ventricular systolic function did not vary significantly between the two groups. However, postoperatively evaluated left ventricular end-diastolic diameter dimensions in the study group were significantly smaller than those in the control group (47.6 +/- 7.9 mm versus 56 +/- 9.5 mm; p = 0.05). Ejection fraction was similar in both groups (56.2% +/- 12.8% for the study [Shelhigh] and 52.6% +/- 16.8% for the control [homograft] group). CONCLUSIONS: Our experience with both the Shelhigh No-React SuperStentless and Stentless Aortic Valve Conduit in patients with native or prosthetic aortic valve endocarditis appears to demonstrate good results, similar to those of cryopreserved homografts. Ease of implantation and favorable effective orifice area and pressure gradients, as well as the No-React anticalcification treatment, are promising factors.

Abscess↗

Outpatients on mechanical circulatory support.

BACKGROUND: As waiting periods for heart transplantation have lengthened, the application of long-term mechanical circulatory support (MCS) has become more common in patients presenting with cardiogenic shock. Anticipating increased long-term MCS, a policy to discharge patients home has been instituted. This study compares the results of outpatient on MCS to a group of patients remaining hospitalized. METHODS: We report our 10-year experience with 108 patients on MCS, who were supported for more than 3 months. Group A consisted of 38 patients (25 Novacor, 13 Berlin Heart) who underwent assist implantation from 1996 to 2001. They had a mean support time of 454 days (range 100 to 1074 days) and spent a mean of 326 days (range 20 to 769 days) at home. Group B consisted of 70 patients (24 Novacor, 46 Berlin Heart) who underwent assist implantation between 1991 and 2000. They had a mean support time of 234 days (range 95 to 795 days) and were not discharged. The patients were monitored for complications, hospital readmissions, and causes of death including infections and thromboembolic and bleeding events during the MCS time. RESULTS: Group A total mortality was 16% (6/38). Two patients died from cerebral embolism, one from cerebral hemorrhage, two from systemic infection, and one from multiorgan failure. Thirty-two patients (84%) required 95 readmissions to the hospital due to cerebral embolism (n = 9), bleeding (n = 1), wound infections (n = 23), coagulation disorder (n = 13) for heart transplantation (n = 5), and (n = 44). In group B the mortality was 43% (30/70) for noncardiac reasons and thus significant higher (p = 0.004, chi2 test). Causes of death were cerebral embolism (n = 5), cerebral hemorrhage (n = 7), systemic infection (n = 14, significantly higher, p = 0.04, chi2 test), and multiorgan failure (n = 4). CONCLUSIONS: Our experience demonstrates that MCS can be used in outpatients without increased mortality and with an acceptable rate of readmissions (2.8/patient). It ensures the survival of the patient, enables recovery from multiorgan failure, and offers an acceptable quality of life.

Adolescent↗

New approach in treatment of acute cardiogenic shock requiring mechanical circulatory support.

In 12 patients with acute cardiogenic shock who required mechanical circulatory support a short-term Abiomed BVS 5000 extracorporeal assist device was implanted using the inflow and outflow cannulas of the BerlinHeart extracorporeal assist device. In 7 patients suitable for long-term support the Abiomed pumps were later exchanged for BerlinHeart pumps. This approach avoids the risks associated with repeat sternotomy and use of cardiopulmonary bypass and decreases the total costs of patient care.

Acute Disease↗

Reducing the incidence and severity of pericardial adhesions with a sprayable polymeric matrix.

PURPOSE: This study was undertaken to evaluate the antiadhesive properties of a polymeric agent in infants undergoing staged surgical correction of congenital heart abnormalities. DESCRIPTION: Sixteen infants having staged surgical repair were treated with a polymeric matrix at the completion of the initial surgery. There were 5 untreated controls. The tenacity and extent of adhesions at five separate regions of the heart were evaluated at the follow-up surgery. EVALUATION: For all sites combined, there was a threefold difference in median tenacity scores in favor of the experimental treatment (1.0 vs 3.0, p < 0.01). Significant differences were achieved separately at the right ventricle and the anterior surface of the great vessels (p = 0.02 for both comparisons). Analysis of adhesion scores reflecting the extent of adhesions similarly favored the experimental treatment for all sites (80 vs 270, p < 0.01), with significant differences persisting at the right atrium (p < 0.01) and the anterior surface of the great vessels (p = 0.04). There were no treatment-related adverse events. CONCLUSIONS: Use of this polymeric agent at the completion of open cardiac surgery may prevent the occurrence or reduce the severity of pericardial adhesions.

Female↗

Elevated donor cardiac troponin T and procalcitonin indicate two independent mechanisms of early graft failure after heart transplantation.

BACKGROUND: Cardiac troponin T (cTnT) >0.1 microg/l and procalcitonin (PCT) >2 microg/l in the serum of heart donors are predictors of early graft failure after heart transplantation (HTx). The current study investigates the relationship between these two markers and their prognostic value when one or both of them are elevated. METHODS: Cardiac TnT and PCT were measured in serum from 92 consecutive brain-dead donors accepted for HTx. The donors were retrospectively divided into two groups: group I (n=78) donors of hearts with good function, group II (n=14) donors of hearts with early graft failure after transplantation. RESULTS: There were no correlations between cTnT and PCT values (r=0.12, P=0.27). In eight donors in group I one or both markers were elevated. In one donor both markers were above the cut-off levels. In 12 donors (86%) in group II one or both markers were elevated. In two donors both markers were above the cut-off levels and in a further two below. There was no significant interaction between the two markers in either group using a logistic regression model (P=0.28). CONCLUSIONS: Elevated cTnT and PCT levels in the serum of heart donors were independent prognostic markers of early graft failure. This fact may suggest two different mechanisms of early graft failure: primary myocardial damage and damage related to systemic inflammatory response. The combination of both markers had a higher sensitivity than each parameter on its own. Their use as additional parameters may improve heart donor selection.

Adult↗

Cannulation of the right axillary artery for surgery of acute type A aortic dissection.

OBJECTIVE: The optimal choice of the arterial inflow site during operations for type A aortic dissection is not clearly defined. The aim of the prospective study was to identify whether cannulation of the right axillary artery instead of the femoral artery may improve the results of surgery for acute type A aortic dissection. METHODS: Seventy consecutive patients were operated on because of acute type A aortic dissection from January 2000 to February 2002. The only difference in surgical strategy was the site of arterial cannulation: the right axillary artery was used in 20 patients [axillary group] and the left femoral artery in 50 patients [femoral group]. All patients had aortic surgery with open distal anastomosis during deep hypothermic arrest and retrograde cerebral perfusion. The mean age was 58.7 +/- 12 years with a range from 28 to 88 years (axillary group, 56.6 +/- 13 years; femoral group, 59.4 +/- 12 years; P = 0.435). Preoperatively evident organ malperfusion was identified in five (25%) patients of the axillary group and in seven (14%) of the femoral group. RESULTS: There was no perioperative death. The hospital mortality rate was 5.0% for the axillary group and 22% for the femoral group (all patients, 17%). Major neurological complications occurred postoperatively in 5% of patients from the axillary group (one out of 20 patients) and in 8% of patients from the femoral group (four out of 50 patients) (all patients, 7%). CONCLUSION: Cannulation of the right axillary artery improved the outcome of surgery for acute type A aortic dissection. However, postoperative complications occurred after both axillary and femoral artery cannulation.

Acute Disease↗

Donor-transmitted coronary atherosclerosis.

BACKGROUND: Autopsies show that coronary atherosclerosis is present frequently in the young and healthy. However, according to our former guideline, we performed pre-transplant evaluation without coronary angiogram in donors <60 years. The purpose of this study is to evaluate to what extent native coronary atherosclerosis is transmitted through heart transplantation. METHODS: Between April 1986 and December 2000, a total of 1253 patients underwent heart transplantation at our institution. If coronary evaluation with coronary angiogram or autopsy had been performed within 6 months after transplantation, we regarded focal and non-circumferential atherosclerosis with >or=50% stenosis in proximal segments of at least 1 coronary vessel of the donor heart as transmitted, native coronary atherosclerosis, rather than newly developed transplant vasculopathy. RESULTS: We excluded 85 of 1253 (6.8%) cases because coronary evaluation was not performed within 6 months (n = 45) or because hearts underwent angiography during pre-transplant evaluation (n = 40). Of these, 2 patients with significant coronary atherosclerosis underwent transplantation and concurrent coronary artery bypass grafting. The prevalence of significant (stenosis >or=50%) and inadvertently transmitted coronary atherosclerosis was 7.0% (82/1168). CONCLUSION: The prevalence of coronary atherosclerosis in patients who underwent angiography within 6 months after transplantation was 5.2% (49/950). Among subjects who had autopsies within the first 6 months after heart transplantation, we found significant coronary atherosclerosis (stenosis >or=50%) 15.1% (33/218), and among those with early graft failure (<10 days after transplantation), the prevalence was 22.8% (26/114). The prevalence of coronary atherosclerosis in the donor pool is high, and donor screening without coronary angiogram overlooks significant coronary atherosclerotic lesions (stenosis >or=50%) in a considerable number of cases (7.0%). Because donor-transmitted coronary atherosclerosis is a risk factor in short-term (early graft failure) survival after heart transplantation, we have now changed our policy to include coronary angiography as a standard in screening donors >or=40 years. However, to what extent donor coronary atherosclerosis is accepted undoubtedly must be made arbitrarily until an evidence-based algorithm becomes available.

Adult↗

Heart transplantation in children after mechanical circulatory support with pulsatile pneumatic assist device.

BACKGROUND: Mechanical support with a pulsatile pneumatic ventricular assist device (VAD) is a complex rescue procedure performed in children with untreatable cardiogenic shock. Its impact on early and long-term survival after subsequent heart transplantation (HTx) remains to be determined. METHODS: We reviewed retrospectively the course of 95 children (median age, 8 years; range, 8 days-17 years; body weight, 24 kg; range, 3-110 kg) who underwent HTx. Group A, the elective-HTx group, consists of 33 children who were treated as outpatients before transplantation. Group B, the emergency-HTx group, has 44 children who were critically ill and hospitalized before transplantation but without ventricular assist devices, whereas Group C, the VAD-HTx group, consists of 18 children resuscitated and supported with pulsatile pneumatic VADs for a median time of 20 days. RESULTS: Overall actuarial survival after cardiac transplantation was 86% at 1 month, 82% at 1 year, and 78% at 5 years, without significant differences among the 3 sub-groups. Group A had the best long-term survival rate, 88% at 1 month, 88% at 1 year, and 80% at 5 years. Group B had a survival rate of 88% at 1 month, 82% at 1 year, and 79% at 5 years. Group C had a survival rate of 72% at 1 month, 72% at 1 year, and 72% at 5 years. We found no differences in neurologic outcome, acute cardiac rejection, or transplant failure. The survival rate was significantly better in the children with cardiomyopathy compared with those with congenital heart defects (p = 0.014). CONCLUSIONS: Bridging to HTx with a pulsatile pneumatic VAD is a safe procedure in pediatric patients. After HTx, overall survival of these children is similar to that of patients who were bridged with inotropes or who were awaiting heart transplantation electively.

Actuarial Analysis↗

Early detection of left ventricular dysfunction related to transplant coronary artery disease.

BACKGROUND: Transplant coronary artery disease (TxCAD) is a major limitation to the long-term success of cardiac transplantation. We assessed left ventricular (LV) function in relation to severity of coronary lesions to improve both early diagnosis of TxCAD and evaluation of the severity of myocardial damage. METHODS: Echocardiographic evaluation of LV function, including pulsed-wave tissue Doppler imaging (PW-TDI) wall motion analysis, was performed in 304 heart recipients before each of their follow-up cardiac catheterizations. LV systolic and diastolic parameters obtained both invasively and non-invasively were tested for their relation to angiographic and intravascular ultrasound (IVUS) findings. RESULTS: LV end-diastolic pressure and most of the PW-TDI parameters differed significantly (p < 0.001) between patients with and without TxCAD. In comparison to patients without the disease, even those with moderate, angiographically non-visible TxCAD showed significant differences for all systolic PW-TDI parameters. Wall motion alterations during angiographic TxCAD were almost always global and related mainly to diffuse Type B lesions. Systolic PW-TDI parameter changes showed highly predictive values for TxCAD. At systolic wall motion peak velocity (Sm) values constantly <10 cm/sec, we found a 97.37% likelihood of TxCAD (angiographically and/or IVUS-visible), whereas Sm values of > or =11 cm/sec excluded angiographic TxCAD with 90.41% probability. CONCLUSIONS: Among all parameters investigated for the evaluation of allograft LV function, PW-TDI systolic parameters were of the greatest diagnostic value. Wall motion assessment allows early detection of myocardial dysfunction and provides information on both local and global LV dysfunction linked to TxCAD, with potential usefulness for both timing of cardiac catheterizations and prognostic evaluation.

Adult↗