Days alive and out of hospital after left ventricular assist device implantation.

AIMS: Implantation of left ventricular assist devices (LVADs) as a bridge to transplant or as destination therapy is increasing. The selection of suitable patients and outcome assessment belong to the key challenges. Mortality has traditionally been a focus of research in this field, but literature on quality of life is very limited. This study aimed to identify perioperative factors influencing patients' life as measured by days alive and out of hospital (DAOH) in the first year after LVAD implantation. METHODS AND RESULTS: This retrospective single-centre cohort study screened 227 patients who underwent LVAD implantation at the University Hospital Duesseldorf, Germany, between 2010 and 2020. First, the influence of 10 prespecified variables on DAOH was investigated by univariate analysis. Second, multivariate quantile regression was conducted including all factors with significant influence on DAOH in the univariate model. Additionally, the impact of all variables on 1 year mortality was investigated using Kaplan-Meier curves to oppose DAOH and mortality. In total, 221 patients were included into analysis. As pre-operative factors, chronic kidney disease (CKD), pre-operative mechanical circulatory support (pMCS), and Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) stadium < 3 were associated with lower DAOH at 1 year [CKD: 280 (155-322) vs. 230 (0-219), P = 0.0286; pMCS: 294 (155-325) vs. 243 (0-293), P = 0.0004; INTERMACS 1: 218 (0-293) vs. INTERMACS 2: 264 (6-320) vs. INTERMACS 3: 299 (228-325) vs. INTERMACS 4: 313 (247-332), P ≤ 0.0001]. Intra-operative additional implantation of a right ventricular assist device (RVAD) was also associated with lower DAOH [RVAD: 290 (160-325) vs. 174 (0-277), P ≤ 0.0001]. As post-operative values that were associated with lower DAOH, dialysis and tracheotomy could be identified [dialysis: 300 (252-326) vs. 186 (0-300), P ≤ 0.0001; tracheotomy: 292 (139-325) vs. 168 (0-269), P ≤ 0.0001]. Multivariate analysis revealed that all of these factors besides pMCS were independently associated with DAOH. According to Kaplan-Meier analysis, only post-operative dialysis was significantly associated with increased mortality at 1 year (survival: no dialysis 89.4% vs. dialysis 70.1%, hazard ratio: 0.56, 95% confidence interval: 0.33-0.94; P = 0.031). CONCLUSIONS: The results of this study indicate that there can be a clear discrepancy between hard endpoints such as mortality and more patient-centred outcomes reflecting life impact. DAOH may relevantly contribute to a more comprehensive selection process and outcome assessment in LVAD patients.

Wearable cardioverter defibrillator multicentre experience in a large cardiac surgery cohort at transient risk of sudden cardiac death.

OBJECTIVES: The wearable cardioverter defibrillator (WCD) is an established, safe, effective solution, protecting patients at risk of sudden cardiac death. We specifically investigated WCD use in cardiac surgery patients since data for this patient group are rare. METHODS: Retrospective data analysis in 10 German cardiac surgery centres was performed. Cardiac surgery patients with left ventricular ejection fraction (LVEF) ≤35% or after implantable cardioverter defibrillator (ICD) explantation who received WCD between 2010 and 2020 were assessed using LifeVest Network data. RESULTS: A total of 1168 patients with a median age of 66 years [interquartile range (IQR) 57-73] were enrolled; 87% were male. Clinical indications included coronary artery bypass grafting (43%), valve surgery (16%), combined coronary artery bypass graft/valve surgery (15%), ICD explantation (24%) and miscellaneous (2%). The median wear time of WCD was 23.4 h/day (IQR 21.7-23.8). A total of 106 patients (9.1%) exhibited ventricular tachycardia. A total of 93.2% of episodes occurred within the first 3 months. Eighteen patients (1.5%) received 26 adequate shocks. The inadequate shock rate was low (8 patients, 0.7%). LVEF improved from a median of 28% (IQR 22-32%) before WCD prescription to 35% (IQR 28-42%) during follow-up. Excluding ICD explant patients, 37% of patients received an ICD. CONCLUSIONS: The risk of sudden cardiac death is substantial within the first 3 months after cardiac surgery. Patients were protected effectively by WCD. Due to significant LVEF improvement, the majority did not require ICD implantation after WCD use. Compliance was high despite sternotomy. This multicentre experience confirms existing data regarding effectiveness, safety and compliance. Therefore, WCD should be considered in cardiac surgery patients with severely reduced LVEF.

Life impact of VA-ECMO due to primary graft dysfunction in patients after orthotopic heart transplantation.

AIMS: Primary graft dysfunction (PGD) is a feared complication after heart transplantation (HTX). HTX patients frequently receive veno-arterial extracorporeal membrane oxygenation (VA-ECMO) until graft recovery. Long-term mortality of patients weaned from VA-ECMO after HTX is comparable with non-ECMO patients. However, impact on quality of life is unknown. This study investigated days alive and out of hospital (DAOH) as patient-centred outcome in HTX patients at 1 year after surgery. METHODS AND RESULTS: This retrospective single-centre cohort study included patients who underwent HTX at the University Hospital Düsseldorf, Germany, from 2010 to 2020. Main exposure was VA-ECMO due to PGD. VA-ECMO and non-VA-ECMO patients were compared regarding the primary endpoint DAOH at 1 year after HTX. Subgroup analysis for patients weaned from VA-ECMO was performed. In total, 144 patients were included into analysis; 1 year mortality was significantly lower in non-ECMO patients [non-ECMO 14.3% (14/98) vs. VA-ECMO 34.8% (16/46), adjusted hazard ratio: 0.32, 95% confidence interval: 0.15-0.74; P = 0.002]. Mortality did not differ significantly between patients weaned from VA-ECMO and non-ECMO patients [non-ECMO 14.3% (14/98) vs. VA-ECMO (weaned) 18.9% (7/37), adjusted hazard ratio: 0.72, 95% confidence interval: 0.27-1.90; P = 0.48]. DAOH were significantly higher in non-ECMO patients compared with VA-ECMO patients and patients weaned from VA-ECMO [non-ECMO vs. VA-ECMO: median 310 (inter-quartile range 277-327) days vs. 243 (0-288) days; P < 0.0001; non-ECMO vs. VA-ECMO (weaned): 310 (277-327) days vs. 253 (208-299) days; P < 0.0001]. These results were still significant after multivariable adjustment with forced entry of predefined covariables. CONCLUSIONS: Despite similar survival rates, VA-ECMO due to PGD has a relevant life impact as defined by DAOH in the first year after HTX. As a more patient-centred endpoint, DAOH may contribute to a more comprehensive assessment of outcome in HTX patients.

Coronary artery bypass grafting under sole Impella 5.0 support for patients with severely depressed left ventricular function.

Selection of the ideal surgical procedure for coronary revascularization in patients with severe cardiac dysfunction at times may represent a challenge. In recent years, with the advent of surgical large microaxial pumps, e.g., Impella 5.0 (Abiomed Inc., Boston, USA), specific support and effective unloading of the left ventricle has become available. In the interventional field, good results have been achieved with smaller microaxial pumps in the setting of so-called protected percutaneous coronary intervention. In this study, we would like to share our early experience with surgical coronary revascularization under the sole support of Impella 5.0, omitting the use of heart-lung machine in three cases of severe cardiac dysfunction due to complex ischemic heart disease. Effective circulatory support intraoperatively and postoperatively speaks in favor of this technique in selected patients.

Risk Factors for Acute Kidney Injury Requiring Renal Replacement Therapy after Orthotopic Heart Transplantation in Patients with Preserved Renal Function.

Acute kidney injury (AKI), requiring renal replacement therapy (RRT). is a serious complication after orthotopic heart transplantation (HTX). In patients with preexisting impaired renal function, postoperative AKI is unsurprising. However, even in patients with preserved renal function, AKI requiring RRT is frequent. Therefore, this study aimed to identify risk factors associated with postoperative AKI requiring RRT after HTX in this sub-cohort. This retrospective cohort study included patients ≥ 18 years of age with preserved renal function (defined as preoperative glomerular filtration rate ≥ 60 mL/min) who underwent HTX between 2010 and 2021. In total, 107 patients were included in the analysis (mean age 52 ± 12 years, 78.5% male, 45.8% AKI requiring RRT). Based on univariate logistic regression, use of extracorporeal membrane oxygenation, postoperative infection, levosimendan therapy, duration of norepinephrine (NE) therapy and maximum daily increase in tacrolimus plasma levels were chosen to be included into multivariate analysis. Duration of NE therapy and maximum daily increase in tacrolimus plasma levels remained as independent significant risk factors (NE: OR 1.01, 95%CI: 1.00-1.02, p = 0.005; increase in tacrolimus plasma level: OR 1.18, 95%CI: 1.01-1.37, p = 0.036). In conclusion, this study identified long NE therapy and maximum daily increase in tacrolimus plasma levels as risk factors for AKI requiring RRT in HTX patients with preserved renal function.

Multimodal mechanical circulatory assist for perioperative biventricular failure.

A 61-year-old woman with acute myocardial infarction (MI), cardiogenic shock, and Impella CP support underwent emergency coronary artery bypass grafting. Postoperatively venous-arterial extracorporeal membrane oxygenation (va-ECMO) became necessary, followed by Impella 5.0 insertion on 7th postoperative day (POD), the addition of right ventricular support by TandemHeart due to inadequate flow of Impella system, which then allowed for va-ECMO weaning. Impella und TandemHeart were removed on 14th POD, 31st POD, respectively. Biventricular decompensation following MI was successfully treated by a sequence of different mechanical circulatory support systems allowing an adaptive weaning strategy.

The analysis of left ventricular ejection fraction after minimally invasive surgery for primary mitral valve regurgitation.

BACKGROUND: Although minimally invasive mitral valve surgery (MIMVS) has become the first choice for primary mitral regurgitation (MR) in recent years, clinical evidence in this field is yet limited. The main focus of this study was the analysis of preoperative (Pre), postoperative (Post), and 1-year follow-up (Fu) data in our series of MIMVS to identify factors that have an impact on the left ventricular ejection fraction (LVEF) evolution after MIMVS. METHODS: We reviewed the perioperative and 1-year follow-up data from 436 patients with primary MR (338 isolated MIMVS und 98 MIMVS combined with tricuspid valve repair) to analyze patients' baseline characteristics, the change of LV size, the postoperative evolution of LVEF and its factors, and the clinical outcomes. RESULTS: The overall mean value of ejection fraction (EF) slightly decreased at 1-year follow-up (mean change of LVEF: -2.63 ± 9.00%). A significant correlation was observed for preoperative EF (PreEF) und EF evolution, the higher PreEF the more pronounced decreased EF evolution (in all 436 patients; r = -.54, p < .001, in isolated MIMVS; r = -.54, p < .001, in combined MIMVS; r = -.53, p < .001). Statistically significant differences for negative EF evolution were evident in patients with mild or greater tricuspid valve regurgitation (TR) (in all patients; p < .05, odds ratio [OR] = 1.64, in isolated MIMVS; p < .01, OR = 1.93, respectively). Overall clinical outcome in New York Heart Association classification at 1 year was remarkably improved. CONCLUSIONS: Our results suggest an excellent clinical outcome at 1 year, although mean LVEF slightly declined over time. TR could be a predictor of worsened follow-up LVEF in patients undergoing MIMVS.

Iron deficiency does not impair the outcome after elective coronary artery bypass and aortic valve procedures.

BACKGROUND AND AIM OF THE STUDY: Iron deficiency (ID), a common malnutrition, has been linked to impaired prognosis in patients with congestive heart failure. It remains unclear whether ID also affects the outcome after elective cardiac surgery. METHODS: A total of 378 consecutive patients undergoing either coronary artery bypass grafting (CABG) or surgical aortic valve replacement (SAVR) were prospectively enrolled, and blood samples were taken before surgery for analysis of iron metabolism. Incidence of major adverse cardiovascular and cerebrovascular events (MACCE) was defined as the primary endpoint of the study. RESULTS: ID (ferritin < 100 ng/ml or ferritin = 100-299 ng/ml and transferrin saturation < 20%) was common in cardiac surgery patients (ID, n = 265, 70%) and related to significant decreased preoperative hemoglobin values (ID: 13.6 ± 1.6 g/dl, Non-ID: 14.3 ± 1.5 g/dl, p < 0.01). We did not observe any differences in the postoperative outcome of the two groups. The incidence of MACCE was 4.9% in patients with ID and 8.8% in Non-ID (p = 0.16). In-hospital mortality (ID: 1.9%, Non-ID: 4.4%, p = 0.17) and stroke (ID: 1.1%, Non-ID: 1.8%, p = 0.64) were also not altered by ID. In addition, intensive care unit and hospital stay, perioperative blood transfusions as well as perioperative morbidities, such as acute kidney injury, low cardiac output syndrome, major bleeding complication, and sternal wound infections were comparable in patients with and without ID. CONCLUSIONS: The majority of patients undergoing elective CABG or SAVR suffer from ID; however, we found no significant differences in regard to MACCE and postoperative morbidity between ID and non-ID patients.

The Course of Circulating Small Extracellular Vesicles in Patients Undergoing Surgical Aortic Valve Replacement.

In the last years, increasing efforts have been devoted to investigating the role of small extracellular vesicles (sEVs) in cardiovascular diseases. These nano-sized particles (30-150 nm), secreted by different cell types, contain signalling molecules that enable participation in intercellular communication processes. In this study, we examined the course of circulating sEVs in patients undergoing surgical aortic valve replacement (SAVR) and correlated them with echocardiographic and standard blood parameters. Peripheral blood samples were collected from 135 patients undergoing SAVR preoperatively and at three follow-up points. Circulating sEVs were precipitated using Exoquick™ exosome isolation reagent and analyzed by nanoparticle tracking analysis (NTA). Our findings indicate that no more than 7 days after SAVR, there was a marked increase of circulating sEVs before returning to initial values after 3 months. Further, shear stress is not a trigger for the formation and release of circulating sEVs. Moreover, we pointed out a correlation between circulating sEVs and erythrocytes as well as LDH and creatinine levels in peripheral blood. Finally, all patients with a moderate prosthesis-patient mismatch as well as with an impaired left ventricular mass regression had lower levels of circulating sEVs 3 months after SAVR compared to their respective status before surgery. We conclude that in patients with aortic valve stenosis (AVS), sEVs may play an important part in mediating cell-cell communication and SAVR may have a crucial and lasting impact on their circulating levels. Besides, lower levels of sEVs portend to be associated with inferior recovery after major surgical interventions. The additional use of circulating sEVs beyond echocardiographic and laboratory parameters could have a prognostic value to estimate adverse outcomes in patients undergoing SAVR.

The age-adjusted Charlson comorbidity index in minimally invasive mitral valve surgery.

OBJECTIVES: Mitral valve repair is the preferred method used to address mitral valve regurgitation, whereas transcatheter mitral valve repair is recommended for high-risk patients. We evaluated the risk-predictive value of the age-adjusted Charlson comorbidity index (aa-CCI) in the setting of minimally invasive mitral valve surgery. METHODS: The perioperative course and 1-year follow-up of 537 patients who underwent isolated or combined minimally invasive mitral valve surgery were evaluated for 1-year mortality as the primary end point and other adverse events. The predictive values of the EuroSCORE II and STS score were compared to that of the aa-CCI by a comparative analysis of receiver operating characteristic curves. Restricted cubic splines were applied to find optimal aa-CCI cut-off values for the increased likelihood of experiencing the predefined adverse end points. Consequently, the perioperative course and postoperative outcome of the aa-CCI ≥8 patients and the remainder of the sample were analysed. RESULTS: The predictive value of the aa-CCI does not significantly differ from those of the EuroSCORE II or STS score. Patients with an aa-CCI ≥8 were identified as a subgroup with a significant increase of mortality and other adverse events. CONCLUSIONS: The aa-CCI displays a suitable predictive ability for patients undergoing minimally invasive mitral valve surgery. In particular, multimorbid or frail patients may benefit from the extension of the objectively assessed parameters, in addition to the STS score or EuroSCORE II. Patients with an aa-CCI ≥8 have a very high surgical risk and should receive very careful attention.

Valve-Sparing Aortic Root Replacement as First-Choice Strategy in Acute Type a Aortic Dissection.

Background: Although, in theory, valve-sparing aortic root replacement (David procedure) is an ideal surgical option for acute aortic dissection type A (AADA) it is usually not regarded as the first-choice treatment due to the emergency setting and the relative complexity of the procedure. Here, we report the results of a consecutive, single-surgeon series of 45 AADA patients with the David procedure as first-choice treatment strategy. Methods and Results: Between September 2009 and July 2013 a total of 49 patients with AADA were consecutively operated by the same surgeon at our institution. The David procedure was the treatment of choice for the proximal aorta unless aortic valve pathology or critical preoperative patient status advocated against it. Median follow-up was 5.0 years (CI95%, 4.0-6.0). Out of the 45 patients included in this study the David procedure was performed in 28 patients (62.2%), while in 17 patients (37.8%) an alternative surgical strategy had to be pursued. Although X-clamping (168.5 ± 41.7 vs. 110.3 ± 51.1 min; p = 0.001), cardiopulmonary bypass (CPB) (245.0 ± 62.4 vs. 211.8 ± 123 min; p = 0.029) and total operation time (383.8 ± 88.5 vs. 312.8 ± 144.8; p = 0.047) were significantly longer in the David-group as compared to the non-David group, there was no difference in major complication rate as well as 30-day (17.9 vs. 23.5%; p = 0.645) and 5-year mortality (28.6 vs. 35.3%) between groups. Conclusions: This small series indicates that the David procedure may be safe and feasible as a primary surgical treatment strategy for AADA.

Relevance of Leaflet Prolapse to the Indication Policy for Aortic Valve-Sparing Root Replacement.

BACKGROUND: In aortic root replacement, "preexisting" or "induced" aortic leaflet prolapse is related to advanced aortic root pathology and can indicate valve repair. Efforts should be made to perform root replacement before leaflet prolapse is in its maximum extent. MATERIALS AND METHODS: Thirty-nine patients with chronic aortic root dilatation and aortic valve regurgitation (AR) underwent a reimplantation procedure. Contrary to 32 of the 39 patients (group A), 7 of the 39 patients (group B) underwent cusp plication for prolapse. For both groups, data related to the diameter at the level of maximal tubular extension, sinotubular junction, sinus of Valsalva, aorto-ventricular junction (AVJ), and aortic annulus were obtained from preoperative computed tomography scans and analyzed comparatively. RESULTS: Group B showed a higher mean AR grade (P = .007), a higher mean diameter at the level of the aortic annulus (P = .038), AVJ (P = .037), and aortic sinus (P <.001) and a higher sinus dilatation index (existing-to-predicted diameter ratio) (P <.001) than group A. The sinus of Valsalva displayed the best predictive value regarding a plicature-indicating prolapse (P <.001; 95% confidence interval [CI]: 0.809-1.013). A diameter >40 mm was accompanied by an odds ratio (OR) of 24.6 (95% CI: 1.29-496.02). During the follow-up period of 29.0 ± 18.4 months (range: 6-62 months), 1 patient (group A) required reoperation 5 years postoperatively for progressive AR. CONCLUSION: The sinus of Valsalva diameter seems to have the greatest prognostic value for the development of prolapse. Our data suggest that root repair should be considered earlier in time before leaflet prolapse is complete, which most likely occurs when root dilatation becomes an aneurysm.

Previous Sternotomy as a Risk Factor in Minimally Invasive Mitral Valve Surgery.

BACKGROUND: Cardiac redo surgery, especially after a full sternotomy, is considered a high-risk procedure. Minimally invasive mitral valve surgery (MIMVS) is a potential therapeutic approach. However, current developments in interventional cardiology necessitate additional discussion regarding the therapy of choice in high-risk patients. In this context, it is necessary to clarify the perioperative and postoperative risks induced by the factor previous sternotomy in the setting of MIMVS. Thus, we present a comparative study analyzing the outcome of MIMVS after previous sternotomy vs. primary operation. METHODS: We identified 19 patients who received isolated or combined mitral valve (MV) surgery via the MIMVS approach after previous full sternotomy (PS group) and compared the results to those of a group of 357 patients who received primary MIMVS (non-PS group). After a propensity score analysis, groups of n = 15 and n = 131, respectively, were subjected to a comparative evaluation. A 1-year follow-up analysis of functional cardiac parameters and clinical symptoms was performed, accompanied by a Kaplan-Meier analysis. RESULTS: Except for the rate of realized MV reconstructions (PS group: 53.8% vs. non-PS group: 85.5%; p = 0.011), no significant differences were to be noted within the intraoperative and early postoperative course. However, patients in the PS group experienced an increased intensive care unit stay length (PS group: 2 days, 95% CI, 1-8 vs. non-PS group: 1 day, 95% CI, 1-2; p = 0.072). The follow-up examinations revealed excellent functional and clinical outcomes for both groups. The Kaplan-Meier analysis displayed no significant difference regarding the postoperative mortality (p = 0.929) related to the patients at risk. CONCLUSION: A previous sternotomy remains a risk factor for MIMVS and demands special attention in the early postoperative period. Nevertheless, the early- and late-term results concerning the functional and clinical outcomes suggest that the MIMVS procedure is satisfactory, even after a full sternotomy.

Continuous Procedural Full-Lung Ventilation During Minimally Invasive Coronary Bypass Grafting.

BACKGROUND: In the past, minimally invasive cardiac surgery (MICS)- coronary artery bypass graft surgery (CABG) alternatives have been introduced that dramatically reduce the invasiveness of standard operative procedures while still showing excellent clinical outcomes. However, in patients with high morbidity, reduced lung function impeding single-lung ventilation is one of the major concerns for MICS-CABG procedures, although those patients might reap the largest benefit from a procedure of reduced invasiveness. METHODS: Here, we describe a simple surgical technique-the fan technique-that allows for continuous full-lung ventilation with unimpeded surgical view during common MICS-CABG procedures. To evaluate the procedural feasibility of this technique, we analyzed intraoperative ventilation measurements of 22 consecutive MICS-CABG patients in whom the fan technique was used. RESULTS: This study demonstrates a significant improvement of standard respiratory measurements during procedural full-lung ventilation using the fan technique as compared with conventional single-lung ventilation (ventilation pressure 21.4 ± 3.2 versus 26.6 ± 3 mbar, p < 0.001; respiratory rate 13.1 ± 1.4 versus 14.4 ± 2.2 breaths per minute, p < 0.001; minute volume 7.4 ± 1.1 versus 6.2 ± 1 L/min, p < 0.0001; Pao2 during ventilation 294.9 ± 74.6 versus 153.2 ± 71 mm Hg, p < 0.0001). CONCLUSIONS: The presented technique may not only enable us to perform MICS-CABG procedures in patients not suitable for single-lung ventilation owing to reduced pulmonary function, but also may soon also become a standard procedure for MICS-CABG surgery, especially with regard to procedures involving complex and time-consuming multivessel revascularizations. However, further studies are strongly warranted to assess whether the fan technique may also decrease postoperative pulmonary complications and benefit clinical outcome indicators.

Xenon does not increase heart rate-corrected cardiac QT interval in volunteers and in patients free of cardiovascular disease.

BACKGROUND: Impaired cardiac repolarization, indicated by prolonged QT interval, may cause critical ventricular arrhythmias. Many anesthetics increase the QT interval by blockade of rapidly acting potassium rectifier channels. Although xenon does not affect these channels in isolated cardiomyocytes, the authors hypothesized that xenon increases the QT interval by direct and/or indirect sympathomimetic effects. Thus, the authors tested the hypothesis that xenon alters the heart rate-corrected cardiac QT (QTc) interval in anesthetic concentrations. METHODS: The effect of xenon on the QTc interval was evaluated in eight healthy volunteers and in 35 patients undergoing abdominal or trauma surgery. The QTc interval was recorded on subjects in awake state, after their denitrogenation, and during xenon monoanesthesia (FetXe > 0.65). In patients, the QTc interval was recorded while awake, after anesthesia induction with propofol and remifentanil, and during steady state of xenon/remifentanil anesthesia (FetXe > 0.65). The QTc interval was determined from three consecutive cardiac intervals on electrocardiogram printouts in a blinded manner and corrected with Bazett formula. RESULTS: In healthy volunteers, xenon did not alter the QTc interval (mean difference: +0.11 ms [95% CI, -22.4 to 22.7]). In patients, after anesthesia induction with propofol/remifentanil, no alteration of QTc interval was noted. After propofol was replaced with xenon, the QTc interval remained unaffected (417 ± 32 ms vs. awake: 414 ± 25 ms) with a mean difference of 4.4 ms (95% CI, -4.6 to 13.5). CONCLUSION: Xenon monoanesthesia in healthy volunteers and xenon/remifentanil anesthesia in patients without clinically relevant cardiovascular disease do not increase QTc interval.

[Chronic inflammatory bowel disease and cardiovascular complications]. / Kardiovaskuläre Manifestationen bei chronisch-entzündlichen Darmerkrankungen.

The most common extraintestinal manifestations of Crohn's disease and ulcerative colitis are iritis and uveitis, primary sclerosing cholangitis (PSC) and nodal erythema and pyoderma gangrenosum. Complications within the cardiovascular system seem to be uncommon, but there are no systematic investigations concerning the epidemiology of these manifestations. There are more than 100 cases reported about pericarditis and perimyocarditis in patients with inflammatory bowel disease. Other patients with Crohn's disease or ulcerative colitis suffer from vasculitis, representing a further mechanism of inflammatory diseases of the cardiovascular system. There are several case reports showing a combination of Takayasu's arteritis and Crohn's disease, and cross-reacting antibodies against gut mucosa and aortic tissue were found. Some patients developed thrombotic complications by activating the coagulation system, which can result in atrial thrombi, embolism of the pulmonary arteries, myocardial infarction and disseminated intravascular coagulopathy (DIC). Furthermore, a few case were reported about atrio ventricular blocks, amyloidosis of the heart, dilative cardiomyopathy and endomyocardial fibrosis in patients with chronic inflammatory bowel disease. Here, a 27-year-old patient with known ulcerative colitis for 2 years is reported, who presented in the authors' department with unstable angina pectoris. Coronary angiographic examination was immediately performed and diffuse intracoronary thrombi were found, which could be removed by the catheter procedure. A myocardial infarction did not develop. Because of positive anti neutrophil cytoplasmic antibodies (p-ANCA) a p-ANCA-positive arteritis of the coronary vessels with intracoronary thromboembolism due to ulcerative colitis was diagnosed. Systematic studies or investigations concerning the epidemiology of the cardiovascular complications are still lacking, so that an overview about the published data is given.

Mismatch repair protein hMSH2 in primary drug resistance in in vitro human malignant gliomas.

OBJECT: The mismatch repair (MMR) system has previously been implicated in acquired chemoresistance in malignant gliomas in humans. Its impact on the primary chemoresistance in glioblastoma multiforme (GBM) has not been determined in detail, however. METHODS: The authors investigated the expression of both the MMR genes (hMSH2, hMLH1, hPMS1, hPMS2, and hMSH6) at the transcriptional level through reverse transcription-polymerase chain reaction and the hMSH2 protein through Western blot and immunohistochemical analysis of tumor tissue and primary cell cultures of 25 in vitro human de novo GBMs without prior experimental treatment. Results of these analyses were compared with data on in vitro chemoresistance to nine drugs that are in general use in glioma therapy. All MMR genes were expressed in the GBMs, with no significant difference among the individual tumors except in one respect; that is, GBMs showed either relatively high levels or barely detectable levels of hMSH2 messenger (m)RNA and protein expression. All multiresistant tumors demonstrated high hMSH2 expression, and all but two of the sensitive tumors exhibited low hMSH2 mRNA levels. CONCLUSIONS: Analysis of the data indicates that functional alterations of the MMR system are involved in the primary drug resistance in in vitro human malignant gliomas. Analysis of hMSH2 expression might therefore predict therapeutic responses in humans with GBMs.