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Biomedical subjects

Christof Schmid

Publications and source records attributed to Christof Schmid.

At least 19 recordsLinked to original sources
PubMed2007

Roles of cyclooxygenase-2 and phosphorylated Akt (Thr308) in cardiac hypertrophy regression mediated by left-ventricular unloading.

OBJECTIVES: Cyclooxygenase-2 is associated with cardiac hypertrophy during chronic heart failure and is regulated through the PI3K/Akt pathway. Cyclooxygenase-2-induced cell growth through Akt phosphorylation was demonstrated in vitro. In chronic heart failure, left ventricular assist devices lead to hypertrophy regression and molecular changes. Therefore, the expression of cyclooxygenase-2, phosphorylated Akt (p-Akt), and p-Erk 1/2, as well as cardiac hypertrophy before and after left ventricular assist device insertion, was investigated. METHODS: In myocardial tissue before and after left ventricular assist device insertion, the expression of cyclooxygenase-2, p-Akt (Thr308), p-Akt (Ser473), and p-Erk 1/2 was demonstrated by immunohistochemistry and quantified by morphometry. Colocalization of cyclooxygenase-2 and p-Akt (Thr308) was investigated by immuno-doublestaining. RESULTS: A significant decrease of cyclooxygenase-2, p-Akt (Thr308), p-Akt (Ser473), and p-Erk 1/2 protein expression and hypertrophy regression was observed after left ventricular assist device insertion. A significant correlation between cyclooxygenase-2 and p-Akt (Thr308) expression, as well as between cyclooxygenase-2 expression and cardiomyocyte diameter, was observed before, but not after, left ventricular assist device insertion. Only cyclooxygenase-2-positive cardiomyocytes showed significant hypertrophy regression on unloading. Sarcoplasmic colocalization of cyclooxygenase-2 and p-Akt (Thr308) is present before left ventricular assist device insertion and is decreased after unloading, whereas the normal myocardium is completely devoid of it. CONCLUSIONS: Left ventricular assist device treatment is associated with a significant decrease of cyclooxygenase-2, p-Akt (Thr308), p-Akt (Ser473), and p-Erk 1/2, and cardiac hypertrophy regression of cyclooxygenase-2-positive cardiomyocytes. The significant correlation and colocalization in cardiomyocytes of cyclooxygenase-2 and p-Akt (Thr308) before left ventricular assist device insertion suggests a cross-talk between the 2 molecules in the progression of cardiac hypertrophy, which is reversibly regulated by the left ventricular assist device.

Adolescent↗
PubMed2006

N-terminal pro-brain natriuretic peptide, kidney disease and outcome in patients with chronic heart failure.

BACKGROUND: In patients with chronic heart failure (CHF), N-terminal pro-brain natriuretic peptide (NT-proBNP) provides relevant prognostic information, but its usefulness in the presence of kidney disease has been questioned. METHODS: We prospectively enrolled 142 patients with stable CHF and a wide spectrum of renal function (estimated glomerular filtration rates [eGFRs] ranging from 17.1 to 100.3 ml/min/1.73 m2). Chronic kidney disease, defined as eGFR < 60 ml/min/1.73 m2, was present in 63 patients (44%). NT-proBNP measurements were carried out on a bench-top analyzer (Elecsys 2010). Cardiac death or urgent cardiac transplantation were considered as a combined study end-point. RESULTS: During a follow-up of 383 +/- 237 days, 19 patients underwent a cardiac event (cardiac death, n = 17; urgent cardiac transplantation, n = 2). By multivariate Cox analysis, including clinical and laboratory variables, NT-proBNP and serum hemoglobin were independent prognostic predictors. In patients with NT-proBNP > 1,129 pg/ml, outcome was significantly worse compared to patients with NT-proBNP < 1,129 pg/ml (event-free survival rate 67% vs 94% in those with NT-proBNP < 1,129 pg/ml, p = 0.001). By linear regression analysis, NT-proBNP levels were related to New York Heart Association (NYHA) functional class (R = 0.41, p < 0.001), and inversely related to eGFR (R = -0.29, p = 0.001) and to left ventricular ejection fraction (R = -0.43, p < 0.001). CONCLUSIONS: In CHF patients with and without kidney disease, NT-proBNP provides independent prognostic information. In such patients, NT-proBNP levels are not only reflective of a reduced clearance (i.e., a lower eGFR) but also of the severity of the underlying structural heart disease.

Adult↗
PubMed2006

Does continuous flow left ventricular assist device technology have a positive impact on outcome pretransplant and posttransplant?

BACKGROUND: Left ventricular assist devices (LVADs) with continuous flow properties are increasingly used to bridge heart failure patients to cardiac transplantation. Advantages in comparison with the pulsatile LVADs are smaller size, better endurance, and lower thromboembolic events. However, whether these new pumps have similar pre- and posttransplant outcomes is not clear. METHODS: Fifty patients with a continuous flow device (Micromed DeBakey, Houston, TX or InCor BerlinHeart, Berlin, Germany) were compared with an age-, disease-, and LVAD duration-matched control group (n = 80) supported with a pulsatile device (Novacor, WorldHeart, Oakland, CA or HeartMate, Thoratec Corp, Pleasanton, CA). RESULTS: Age (44.3 +/- 13.4 vs 46.1 +/- 11.1 years), disease (idiopathic dilated cardiomyopathy, 58% vs 65%), and LVAD duration (138 +/- 131 vs 128 +/- 106 days) were comparable in both groups. Successful bridging to transplantation was similar with continuous flow in comparison with pulsatile device support (52% vs 56%, p = not significant [NS]). Thirty-day mortality after cardiac transplantation in patients with continuous flow LVAD support was 21.7% vs 22.2% with pulsatile LVADs (p = NS). Reasons for death were similar among the different LVAD groups. Long-term survival was similar in both LVAD groups compared with patients without previous LVAD support. Interestingly, severe rejections were significantly more frequent in patients with a continuous flow LVAD (p < 0.001). CONCLUSIONS: The new generation of cardiac assist devices with continuous flow pattern has a similar rate of pre- and posttransplant mortality in comparison with pulsatile LVADs. However, the rate and severity of posttransplant rejection was significantly higher in the group with continuous flow devices. Further studies are warranted to explain the higher rate of severe rejections.

Adult↗
PubMed2006

Reversible pulmonary hypertension in heart transplant candidates: to transplant or not to transplant.

BACKGROUND: Pulmonary hypertension (PHT), defined as a pulmonary vascular resistance (PVR) greater than 2.5 Wood units [WU] and(or) transpulmonary gradient (TPG) greater than 12 mm Hg, is a risk factor for mortality in cardiac transplantation due to elevated postoperative right heart failure. Orthotopic heart transplantation is possible if PVR could be reversed below 2.5 WU and TPG below 12 mm Hg. We show the Muenster experience from the last 10 years. METHODS: From April 1996 to December 2005 all cardiac transplant recipients separated into patients with and without PHT were included. All patients with PHT had successful reduction (PVR < or = 2.5 WU and TPG < or = 12 mm Hg) using prostaglandin I2 or E1. Posttransplant early and late mortality and incidence of right heart failure were studied. RESULTS: Two hundred seventeen patients were included in this study. Of these, 168 had normal pulmonary pressures (non-PHT group), 49 (22.6%) had reversible PHT (rev-PHT group). Mean PVR was 1.6 +/- 1.1 WU vs 2.1 +/- 1.1 WU (p < 0.01; non-PHT vs rev-PHT) and mean TPG 8.0 +/- 1.9 mm Hg vs 10.6 +/- 4.1 mm Hg (p = not significant [NS]). Thirty-day survival after orthotopic cardiac transplantation was 85% vs 78% (p = 0.150) and 10 year survival 63% vs 61% (p = NS). Right heart failure during the first 30 days after transplantation occurred in 27% in the non-PHT group and in 64% in the rev-PHT group (p = 0.035). However, in patients transplanted after 2001 it did not appear. CONCLUSIONS: Cardiac transplant candidates with reversible PHT have still significantly elevated pulmonary pressures compared with patients without PHT. Despite a significantly higher risk of right heart failure, long-term survival after orthotopic cardiac transplantation was not affected.

Adult↗
PubMed2005

Partial left ventriculectomy and mitral valve repair: favorable short-term results in carefully selected patients with advanced heart failure due to dilated cardiomyopathy.

BACKGROUND: Because of the scarcity of donor hearts, surgical alternatives to heart transplantation, such as partial left ventriculectomy (PLV), were introduced for treatment of advanced heart failure. Here, we report our experience with this procedure performed in combination with mitral valve repair. METHODS: Twelve patients with dilated cardiomyopathy (DCM), New York Heart Association (NYHA) class exceeding III on maximal medical therapy, cardiac index of 2.5 liter/min/m2 or less, VO2max of 14 ml/kg/min or less, left ventricular end-diastolic diameter (LVEDD) of 7.0 cm or more, and grade II or greater mitral incompetence, were selected for PLV and mitral valve reconstruction (MVR). Echocardiography, hemodynamics, spiroergometry, and clinical assessment were performed before and 1 year after the operation. RESULTS: One-year survival was 83.3%. All 10 surviving patients were free from failure of the procedure 1 year post-operatively. From pre-operatively to 1 year post-operatively, NYHA functional class improved from 3.3 +/- 0.3 to 1.9 +/- 0.2 (p < 0.001), cardiac index increased from 2.0 +/- 0.2 liter/min/m2 to 2.9 +/- 0.2 liter/min/m2 (p < 0.001), stroke volume index from 25.9 +/- 4.8 ml/m2 to 40.3 +/- 7.3 ml/m2 (p = 0.008), and VO2max from 10.9 +/- 2.4 ml/kg/min to 16.0 +/- 3.6 ml/kg/min (p = 0.016), whereas LVEDD decreased from 8.4 +/- 0.6 cm to 6.6 +/- 0.3 cm (p < 0.001), left ventricular end-systolic diameter from 6.8 +/- 0.8 cm to 5.3 +/- 0.5 cm (p < 0.001), and mitral incompetence from 2.4 +/- 0.6 to 0.9 +/- 0.6 (p < 0.001). Pulmonary pressures and fractional shortening did not change significantly (p > 0.05). Four patients received an implantable cardioverter/defibrillator as a result of their pathologic electrophysiologic examination. CONCLUSIONS: In carefully selected patients, PLV combined with MVR achieves short-term results comparable to that after heart transplantation. However, long-term results and multicenter evaluation will be needed to define its place in the treatment of advanced heart failure.

Cardiac Surgical Procedures↗
PubMed2005

Reverse remodeling following insertion of left ventricular assist devices (LVAD): a review of the morphological and molecular changes.

Left ventricular assist devices (LVAD) are used to "bridge" patients with end-stage heart failure until transplantation of a donor heart can be performed ("bridge to transplantation"). However, in a subset of patients, support by LVAD sporadically results in improved cardiac function, with heart transplantation no longer necessary even after removal of the LVAD ("bridge to recovery"). Also, LVAD appears to be an optional treatment alternative to heart transplantation in patients with contraindications for organ replacement ("destination therapy"). The processes resulting in these effects have descriptively been termed "reverse remodeling". Although the molecular mechanisms are incompletely understood at present, there are several aspects of the reverse remodeling process that have been identified in the past. Alterations of many molecular pathways are involved in the development of chronic heart failure. Some of these appear to be reversible and have been shown to be regulated by LVAD treatment. LVAD lead to lowered cardiac pressure and volume overload in the myocardium followed by decreased ventricular wall tension, reduced cardiomyocyte hypertrophy, improved coronary perfusion and decreased chronic ischemia. Improved coronary flow and myocardial perfusion as well as decreased ventricular wall tension may possibly alter the molecular systems involved in the development of chronic cardiac insufficiency. Aside from describing the morphological changes, this review focuses on the roles of signal transduction, transcriptional regulation, apoptosis, stress proteins, matrix remodeling, and neurohormonal signaling in the failing human heart before and after mechanical circulatory support.

Adrenergic beta-Agonists↗
PubMed2005

First clinical experience with the Incor left ventricular assist device.

BACKGROUND: The Incor (Berlin Heart AG, Germany) is a small (200 g), implantable, magnetically accentuated axial flow pump (non-pulsatile flow) designed to support the left ventricle for extended periods of time. We report on the first single-center clinical experience with this device. METHODS: The Incor was studied in 15 consecutive patients (10 men, 5 women), 24 to 59 years of age. Underlying heart disease was end-stage ischemic heart disease (n = 5), acute myocardial infarction (n = 4), dilated cardiomyopathy (n = 3), acute myocarditis (n = 2) and Chagas disease (n = 1). All patients were in New York Heart Association (NYHA) Class IV heart failure. Four patients had prior open heart surgery. Implantation via cannulation of the left ventricular apex and the ascending aorta was elective in 6 patients and on an emergency basis in 9. RESULTS: No early bleeding complications were seen, but late bleeding occurred in 4 patients. Minor cerebral thromboembolic events with transient neurologic symptoms occurred in 3 patients; severe stroke had to be treated in 1 patient. Systemic emboli were seen in 2 patients. Thrombus-related pump dysfunction was suspected in 3 patients, and managed by intensifying anti-coagulation. Five patients were successfully transplanted after a support interval of 90 to 156 days; 1 patient could be weaned from the system after 171 days. Six patients died during support, 9 to 63 days after device implantation. The remaining 3 patients are still under support, with excellent quality of life. CONCLUSIONS: The Incor is a left ventricular assist device (LVAD) with transplant and adverse event rates comparable to those of other modern ventricular support devices. Its advantages include the small pump chamber, the virtual absence of device-related infections, and the extraordinary convenience during implantation and explantation.

Adult↗
PubMed2005

Long-term support of 9 patients with the DeBakey VAD for more than 200 days.

OBJECTIVE: Pulsatile left ventricular assist devices serving as mechanical circulatory support for patients with end-stage heart failure are associated with complications, including bleeding, thromboembolism, and infection. Axial-flow pumps might overcome some of these shortcomings. Here we report our experience with long-term application of the DeBakey VAD (MicroMed Technology, Inc, Houston, Tex). METHODS: Nine male transplant candidates (37 +/- 14 years) with severe hemodynamic compromise (cardiac index, 1.6 +/- 0.5 L . min(-1) x m(-2); pulmonary capillary wedge pressure, 27 +/- 6 mm Hg) and beginning end-organ failure despite inotropic and intra-aortic balloon pump support received the DeBakey VAD. Clinical outcome was evaluated. RESULTS: Cumulative support was 7.8 years, and the mean duration of support was 314 +/- 75 days (range, 229-438 days). Eight patients were transplanted, and one died from intracerebral bleeding. Peripheral circulation and end-organ function recovered rapidly after implantation. Continuous flow was able to maintain adequate organ perfusion over the long term. Eight patients were discharged during support, with good quality of life. There were no early bleedings, but there were late bleedings in 3 patients caused by excessive anticoagulation and platelet inhibition. Neurologic events occurred in 4 patients. Three patients recovered completely from symptoms, and one had lethal intracerebral bleeding. Because of thrombus formation, the device was exchanged in 4 patients. With increasing experience, thrombolysis was performed in similar situations. All such patients underwent successful transplantation. Hemolysis occurred, with events indicating thrombus formation. Device-related infection was found in one patient. CONCLUSIONS: The DeBakey VAD demonstrated its potential for long-term bridge to transplantation. The risk for thrombus formation needs to be addressed by improvement of pump technology and new strategies for platelet inhibition.

Adolescent↗
PubMed2005

High level of cerebral microembolization in patients supported with the DeBakey left ventricular assist device.

OBJECTIVE: Microembolic signals detected by transcranial Doppler ultrasonography have been demonstrated to be clinically relevant in patients supported with pulsatile left ventricular assist devices. We prospectively investigated the quantity of microembolic signals in patients supported with the continuous-flow DeBakey left ventricular assist device (MicroMed DeBakey VAD; MicroMed Technology, Inc, Houston, Tex) including the refined Carmeda BioActive Surface system (Carmeda AB, Stockholm, Sweden). METHODS: Twenty-three patients (20 male) aged 14 to 62 years supported with DeBakey left ventricular assist devices (n = 6 with Carmeda) were enrolled in this study. Microembolic signal monitorings were performed twice weekly by insonating the middle cerebral artery for 20 minutes without and 20 minutes with oronasal application of oxygen (6 L/min). Evidence of clinically manifest thromboembolic events was based on regular questionnaires, clinical examinations, and results of diagnostic procedures. RESULTS: Despite a low incidence of thromboembolic complications (0.24 per 100 left ventricular assist device days), 20 patients (87%) showed circulating microemboli. Overall, microembolic signals were found in 175 of 499 transcranial Doppler ultrasonographic examinations (35.1%), with mean counts of 81.2 +/- 443 (range 0-5042 signals/h). Both microembolic signal prevalence (25% vs 34%, P = .01) and absolute signal counts (46.5 vs 104, P < .01) significantly declined with oxygen delivery. There was no significant correlation between the individual microembolic signal activity and the incidence of clinical thromboembolism or the intensity of antihemostatic treatment. Patients supported with the Carmeda device did not show reduced rates of clinical thromboembolization or cerebral microemboli. CONCLUSION: In patients with DeBakey left ventricular assist devices, a high load of clinically silent microemboli can be detected within the cerebral arteries despite a low incidence of embolic complications. It needs to be investigated whether such continuous, presumably gaseous microembolization causes cognitive or neuropsychologic deficits.

Adolescent↗
PubMed2005

Can Doppler time domain analysis of microembolic signals discriminate between gaseous and solid microemboli in patients with left ventricular assist device?

OBJECTIVE: Microembolic signals (MES) can be detected by transcranial Doppler sonography (TCD). To identify gaseous microemboli the inhalation of oxygen is an established method in patients with prosthetic heart valves. Time domain analysis of sample volume length (SVL) and of frequency modulation showed promising results in the discrimination between solid and gaseous microemboli. We investigated whether these time domain analyses allow the discrimination of different types of microemboli in patients with the non-pulsatile DeBakey left ventricular assist device (LVAD). MATERIALS AND METHODS: Repeated unilateral detection of MES was performed by TCD in 20 patients supported with DeBakey LVAD. Each monitoring session consisted of 20 minutes without and 20 minutes with inhalation of 100% oxygen (6 l/min). A total of 500 MES, detected with (n=250) or without (n=250) the supply of oxygen, were randomly chosen for offline analysis. The SVL (in cm) was calculated by duration and velocity of the MES measured in the time domain mode. Additionally, frequency modulation of MES was classified into three main types: Without modulation (type I), with gradual changes (type II) and with rapid changes (type III). RESULTS: With oxygen supply, both prevalence (26.4% versus 36.2%, p<0.01) and mean counts of MES per hour (49+/-293 versus 108+/-550, p<0.001) significantly declined compared with the MES load while breathing room air. There was no significant difference in the SVL of MES under oxygen (0.85+/-0.38 cm) compared with those without oxygen delivery (0.92+/-0.37 cm, p=0.6). Furthermore, no significant differences were noted for the MES frequency modulation types in time domain analysis with regard to oxygen supply. CONCLUSIONS: The reduction of MES under oxygen delivery confirms the gaseous nature in a substantial number of circulating microemboli produced by the DeBakey LVAD. However, SVL and frequency modulation of MES did not appear to provide valuable information regarding the structural nature of the underlying microembolic material.

Brain↗
PubMed2004

Left ventricular assist device support reverses altered cardiac expression and function of natriuretic peptides and receptors in end-stage heart failure.

OBJECTIVE: Atrial (ANP) and B-type natriuretics peptides (BNP) via their guanylyl cyclase-A (GC-A) receptor not only regulate arterial blood pressure and volume but also exert local antihypertrophic, antifibrotic and lusitropic effects in the heart. To elucidate whether cardiac hypertrophy/insufficiency and reversal is associated with changes in the local responsiveness to NPs, we compared the mRNA expression of ANP, BNP and receptors and the responsiveness of GC-A to ANP in left ventricular tissue obtained from 10 patients with congestive heart failure (CHF) before and after hemodynamic unloading by left ventricular assist device (LVAD) support. METHODS AND RESULTS: Quantitative "real time" RT-PCR demonstrated that the mRNA expression levels of ANP, BNP and the NP-metabolizing NPR-C receptor were both markedly increased in human failing hearts. GC-A mRNA expression levels were not different from nonfailing hearts, but cGMP production by GC-A in response to ANP was nearly abolished. Reversal of cardiomyocyte hypertrophy during LVAD support was accompanied by normalization of ANP, BNP and NPR-C mRNA levels and a significant recovery of GC-A responsiveness to ANP. CONCLUSION: In CHF patients, increased local clearance by NPR-C receptors and diminished responsiveness of cardiac GC-A might impair the local antihypertrophic effects of natriuretic peptides and contribute to the progression of cardiac hypertrophy and insufficiency. Reverse remodeling during LVAD support reverses these changes and can thereby recuperate the local protective effects of ANP and BNP.

Adolescent↗
PubMed2004

Preoperative chemotherapy with and without additional radiochemotherapy: benefit and risk for surgery of stage III non-small cell lung cancer.

OBJECTIVE: Multi-modality approaches are increasingly employed to improve prognosis in surgically treated stage III non-small cell lung cancer (NSCLC). Risk and benefit of the preoperative therapeutic chemotherapy or combined radiochemotherapy on surgical morbidity and mortality are still a matter of debate. METHODS: In 1995, a national phase III trial was started to compare (arm A) preoperative chemotherapy followed by twice-daily chemoradiation and consecutive surgery, with (arm B) preoperative chemotherapy alone followed by surgery and consecutive radiotherapy. An interim analysis with 277 patients was performed to assess surgical risk and complication rates. RESULTS: of the 358 patients, 273 (71%) underwent thoracotomy, 130 (73%) in arm A and 143 (69%) in arm B. Of the 273 patients undergoing thoracotomy, 168 had stage IIIB disease. Complete resection (R0) was achieved in 212 patients (78%), 104 in arm A (80%) and 108 in arm B (76%) (P=n.s.). There was no difference in the proportion of complex resections between treatment arms (41% in arm A; 48% in arm B). Whilst bronchial stump insufficiency (3.8 vs 2.1%) and bleeding requiring re-thoracotomy (1.5 vs 0.7%) prevailed slightly in arm A, the occurrence of pneumonia divided similar in both treatment arms (4.6 vs 4.9%). Surgical mortality reached 6.1% in arm A (8/130) and 5.6% in arm B(6/143) (P=n.s.). CONCLUSIONS: In both treatment arms, a similar percentage of patients could be forwarded to surgery, even in stage IIIB disease. Bimodality induction seems to be superior with regard to resection rates (R0) (n.s.), but was associated with a higher complication rate, especially bronchial stump insufficiency.

Antineoplastic Agents↗
PubMed2004

Aminoterminal pro type B natriuretic peptide as a predictive and prognostic marker in patients with chronic heart failure.

BACKGROUND: B-type natriuretic peptide (BNP) is released from the cardiac ventricles in response to increased wall tension. We studied the relation of NT-proBNP to Heart Failure Survival Score (HFSS) and New York Heart Association (NYHA) class in patients with chronic heart failure (CHF). We also studied the impact for recipient selection for cardiac transplant and assessed it as a predictive and prognostic marker of CHF. METHODS: A total of 550 patients with dilative cardiomyopathy (n = 323), and coronary artery disease (n = 227) were prospectively examined. All patients underwent spiroergometry, echocardiography, right heart catheterization, and electrocardiogram. Routine blood levels and NT-proBNP were measured. The clinical selection for cardiac transplant candidates was adjudicated by 2 independent cardiologists who were blinded to the results of NT-proBNP assays. Clinical outcome and predictive power of NT-proBNP were analyzed. RESULTS: NT-proBNP levels in patients clinically considered for cardiac transplantation were significantly higher (2293 ng/ml vs 493 ng/ml; p < 0.001). The receiver operating characteristic (ROC) analysis regarding transplant candidacy showed an area under the ROC curve (AUC) of 0.84 +/- 0.01 for HFSS, 0.86 +/- 0.001 for NYHA, and 0.96 +/- 0.01 for NT-proBNP. Patients with increasing NT-proBNP levels or remaining elevated levels despite adequate heart insufficiency treatment were maintained with left ventricular assist device implantation (n = 10) or urgent heart transplantation (n = 2). Patients with NT-proBNP levels above 5000 pg/ml had a mortality rate of 28.4% per year. Twenty-eight patients died during the observation period; all these patients were within NYHA Classes 3 and 4 (NT-proBNP 5423 +/- 423 ng/ml). CONCLUSIONS: NT-proBNP discriminates patients at high likelihood of being a candidate for transplantation and provides prognostic informations in patients with CHF. NT-proBNP levels above 5000 pg/ml at admission were associated with death, and these levels markedly discriminated candidates for left ventricular assist devices or urgent transplantation.

Cardiac Catheterization↗