Factors influencing in-hospital mortality for salvage percutaneous transjugular intrahepatic portosystemic shunting in cirrhotic patients with recalcitrant variceal bleeding after failed endoscopic intervention.

BACKGROUND: Endoscopic therapy is the first-line treatment of choice for control of acute variceal bleeding (AVB). In high-risk patients with persistent AVB despite pharmacological treatment and endoscopic intervention, percutaneous transjugular intrahepatic portosystemic shunting (TIPS) provides a minimally invasive salvage method to reduce portal pressure and control bleeding. OBJECTIVES: To evaluate factors influencing in-hospital mortality after salvage TIPS (sTIPS) in patients with exsanguinating variceal bleeding despite medical treatment and endoscopic intervention. METHODS: Clinical and laboratory data were analysed in all patients treated with sTIPS following failed endoscopic therapy for AVB between August 1991 and November 2020. Factors associated with and predictors of death were determined using bivariate analysis and univariate logistic regression analysis. RESULTS: Thirty-four patients (29 men, 5 women), mean age 52 years (range 31 - 80), received sTIPS for uncontrolled (n=11) or refractory (n=23) AVB. The causes of portal hypertension were alcohol-related (n=24) and non-alcohol-related cirrhosis. Salvage TIPS controlled bleeding in 32 patients, with recurrence in 1. Ten patients died in hospital (mean 4.8 days, range 1 - 10) of liver failure (n=4), multiorgan failure (n=3), alcoholic cardiomyopathy (n=2) and uncontrolled gastric variceal bleeding (n=1). On bivariate analysis, factors associated with death were Child-Pugh (C-P) score ≥10 (p=0.006), sodium Model for End-stage Liver Disease (MELD-Na) score ≥22 (p<0.001), ≥8 units of blood transfused (p<0.001), Sengstaken-Blakemore balloon tube placement (p<0.001), endotracheal intubation (p<0.001), inotropic support (p<0.001) and endoscopically uncontrolled bleeding (p<0.001). Univariate logistic regression analysis showed that the most significant predictors of mortality were inotrope dependency (odds ratio (OR) 134; p<0.001), endotracheal intubation (OR 99; p<0.001), endoscopically uncontrolled bleeding (OR 28; p=0.001), grade 3 ascites (OR 20.9; p=0.012) and C-P grade C (OR 8.8; p=0.011). CONCLUSION: Salvage TIPS controlled variceal bleeding in 94% of patients after failed endoscopic therapy with 29% in-hospital mortality. The most significant predictors of mortality were C-P grade C, grade 3 ascites, inotrope requirement, endotracheal intubation and endoscopically uncontrolled bleeding.

Relation of impaired interorgan communication and parasympathetic activity in chronic heart failure and multiple-organ dysfunction syndrome.

BACKGROUND: We investigated the relationship of impaired autonomic function and severity of illness in chronic heart failure (CHF) and multiple-organ dysfunction syndrome (MODS) as an end stage of CHF. Furthermore, we assessed the link of parasympathetic modulation of the heart rate and inflammatory activation in CHF and MODS. METHODS: Sixty-five patients admitted for worsening of CHF were retrospectively enrolled in this study. In addition, 65 age- and sex-matched patients with pronounced MODS were assigned for comparison of autonomic function and C-reactive protein in patients with CHF or MODS, respectively. Heart rate variability (HRV) parameters of the time and frequency domain as markers of autonomic function were analyzed from 24-hour Holter electrocardiograms. RESULTS: The more pronounced the severity of illness as expressed by the Acute Physiology and Chronic Health Evaluation score, the more the HRV was impaired. This effect was particularly seen for overall variability (SD of RR intervals) and HRV parameters characterizing the parasympathetic modulations of the heart rate (high, very low frequency power). C-reactive protein levels as markers of inflammation were inversely related to high and very low frequencies. CONCLUSION: Our results allow for speculation that autonomic dysfunction in CHF indicates a beginning of uncoupled interorgan communication potentially leading to MODS as characterized by disruption of communication between the organs.

Leiomyosarcoma of the inferior vena cava extending into the right atrium. A rare differential diagnosis of a right atrial tumor with fatal outcome.

A 54-year-old female patient presented with a progressive and deteriorating dyspnea at the slightest exertion in particular during the past few days before presentation. Transthoracic echocardiography revealed a large space-occupying lesion in the right atrium extending into the inferior vena cava (IVC). Abdominal magnetic resonance aortography showed an elongated space-occupying lesion in the IVC with a significant portion of the tumor and almost completely filling the right atrium accompanied by an infiltration of the hepatic and renal veins. A pronounced tumor infiltration of the IVC at the level of the liver was confirmed intraoperatively and immunohistochemical analysis showed a moderate to poorly differentiated leiomyosarcoma. The extended tumor was successfully removed by a complex operation of the thorax and abdomen but the procedure was accompanied by severe bleeding. A few hours following the procedure the patient died due to a further episode of irreversible intra-abdominal hemorrhage.

Expression of androgen-binding protein (ABP) in human cardiac myocytes.

Cardiomyocytes are known to be androgen targets. Changing systemic steroid levels are thought to be linked to various cardiac ailments, including dilated cardiomyopathy (DCM). The mode of action of gonadal steroid hormones on the human heart is unknown to date. In the present study, we used high-resolution immunocytochemistry on semithin sections (1 microm thick), IN SITU hybridization, and mass spectrometry to investigate the expression of androgen-binding protein (ABP) in human myocardial biopsies taken from male patients with DCM. We observed distinct cytoplasmic ABP immunoreactivity in a fraction of the myocytes. IN SITU hybridization with synthetic oligonucleotide probes revealed specific hybridization signals in these cells. A portion of the ABP-positive cells contained immunostaining for androgen receptor. With SELDI TOF mass spectrometry of affinity purified tissue extracts of human myocardium, we confirmed the presence of a 50 kDa protein similar to ABP. Our observations provide evidence of an intrinsic expression of ABP in human heart. ABP may be secreted from myocytes in a paracrine manner perhaps to influence the bioavailabity of gonadal steroids in myocardium.

Damaged myocytes as detected by the colocalization of DNA fragmentation and tissue transglutaminase and their prognostic significance in enterovirus-associated dilated cardiomyopathy.

BACKGROUND: Apoptotic cardiac myocytes have been described in chronic heart failure, but no data exist on the relationship between these 'damaged' myocytes and myocardial detection of enterovirus RNA often associated with dilated cardiomyopathy (DCM). DESIGN: In patients with idiopathic DCM, endomyocardial biopsy samples were studied for enteroviral RNA by one step reverse transcription-polymerase chain reaction (PCR) and a subsequent hybridization of the PCR product using a Southern blot technique. The endomyocardial biopsies were further investigated for markers of cell damage and apoptosis: DNA fragmentation and expression of tissue-transglutaminase (TTG) in the myocytes using the in-situ endlabelling method or an anti-TTG-staining, respectively. To assess the prognostic significance of these two markers the correlation between the percentage of myocytes positive both for DNA fragmentation and TTG (the index of damaged myocytes) and the hemodynamic course of the patients during a mean follow-up period of 15.9 +/- 6.2 months was investigated prospectively by echocardiography. RESULTS: In 14 (45%) of the 31 patients with idiopathic DCM, enteroviral RNA was found in the endomyocardial biopsy samples, while 17 patients (55%) were enterovirus-negative. In enterovirus-positive patients, the index of 'damaged' myocytes was significantly lower (10.7 +/- 4.9% vs. 19.2 +/- 8.8%, P = 0.002) and the left ventricular ejection fraction (LVEF) improved significantly (P = 0.00017 vs. P = 0.13) during long-term follow-up. In addition, a weak negative correlation was seen between the index of damaged myocytes and the changes in LVEF in all patients during long-term follow-up (r = - 0.48, P = 0.004). CONCLUSION: Our results favour the view that enterovirus-positive patients with DCM have less damaged myocytes and a better haemodynamic course than enterovirus-negative patients.

[Leptin: a parameter for metabolic changes in heart failure]. / Leptin: Ein Parameter für metabolische Veränderungen der Herzinsuffizienz.

OBJECTIVE: Advanced chronic heart failure is a hypercatabolic state with an imbalance between anabolic and catabolic metabolism and finally progressive loss of both muscle mass and adipose tissue. Leptin, the product of the obesity gene, is a hormone secreted by adipocytes. Therefore, we tested the hypothesis that plasma leptin concentrations are reduced in advanced chronic heart failure. METHODS: In 20 patients with chronic congestive heart failure (LVEF 23 +/- 6%) and 20 healthy controls (LVEF 65 +/- 8%) matched for gender, age, and body mass index, fasting plasma leptin (ELISA) and TNF alpha (ELISA) were measured. Follow-up examination was performed after 1 year. RESULTS: The fasting plasma leptin concentrations of patients with NYHA grade III (8.4 +/- 3.8 ng/ml*) and NYHA grade IV (4.6 +/- 2.4 ng/ml dagger) were significantly lower as compared with the controls (11.2 +/- 3.1 ng/ml; *p < 0.05, dagger p < 0.01). In patients with NYHA grade II plasma leptin levels were significantly elevated as compared with the healthy controls (14.9 +/- 4.2 ng/ml). TNF alpha was higher in heart failure patients than in healthy controls (8.6 +/- 3.6 pg/ml; 5.9 +/- 2.1 pg/ml; respectively; p < 0.05), but did not correlate with the NYHA functional class. Mortality of the controls was 0%, whereas 15% (n = 3) in the congestive heart failure group; one patient (5%) needs an urgent heart transplantation. All of those patients had leptin concentrations below 5 ng/ml. CONCLUSIONS: Plasma leptin concentrations correlate with the NYHA functional class suggesting anabolic metabolism in NYHA class II and catabolic metabolism in advanced heart failure which might be of prognostic relevance.

Recovery of the cardiac adrenergic nervous system after long-term beta-blocker therapy in idiopathic dilated cardiomyopathy: assessment by increase in myocardial 123I-metaiodobenzylguanidine uptake.

UNLABELLED: In chronic heart failure, elevated plasma norepinephrine (NE) levels and a disparity between the neuronal release and the effective reuptake of NE lead to an increased concentration of NE in the presynaptic cleft, causing a downregulation of the myocardial beta-adrenoceptors. The clinical and prognostic effectiveness of beta-blocker therapy has been shown in patients with chronic heart failure in several large trials. The purpose of this study was to investigate the effect of long-term beta-blocker therapy on the cardiac adrenergic nervous system as assessed by the myocardial uptake of 123I-metaiodobenzylguanidine (MIBG), an analog of NE, in idiopathic dilated cardiomyopathy (IDC). METHODS: In 10 patients with IDC and stable chronic heart failure the myocardial MIBG uptake was measured at baseline and at 1 y (median, 11.5 mo) after treatment with beta-blockers (metoprolol, n = 5; bisoprolol, n = 1; and carvedilol, n = 4) in addition to standard medication. In parallel with the changes in MIBG uptake, the New York Heart Association functional class, the left ventricular ejection fraction (LVEF), and the left ventricular end-diastolic diameter (LVEDD) were documented before and after 1 y of therapy with beta-blockers. RESULTS: During the 1-y follow-up, a significant increase in myocardial 123I-MIBG uptake (P = 0.005) in parallel with an improved LVEF (P = 0.005) and a reduced LVEDD (P = 0.019) was found. A trend toward an improvement of the New York Heart Association functional class under the beta-blocker therapy (P = 0.139) was also found. CONCLUSION: Assessment of the myocardial 123I-MIBG uptake is a useful noninvasive tool for evaluating changes in cardiac sympathetic nerve activity under medical therapy. Long-term treatment with beta-blockers in IDC causes a recovery of the cardiac adrenergic nervous system concomitantly with a clinical and hemodynamic improvement.

Actin in semithin sections of myocardial biopsies as a tool to visualize myofibrillary degradation in humans.

Dilated cardiomyopathy (DCM) is characterized by dilation of ventricular walls and the reduction of cardiac contractillity, caused by loss of myofibrils and apoptosis of the myocytes. Histochemical assessment of myocardial biopsies is commonly used to monitor these events. Here we report the use of immunohistochemistry for alpha-actin in semithin serial sections of myocardial biopsies taken from patients with various stages of DCM. This technique allows also the detection of DNA-fragmentation and tissue transglutaminase as markers for cell damage in subsequent sections of the same myocytes. Intense actin immunostaining was observed only in the cytoplasm of cells that also expressed tissue transglutaminase in the cytoplasm and showed DNA-fragmentation in the nucleus. We assume that endogenous proteolysis, associated with apoptotic events enhances the stainability of actin in semithin sections. High resolution detection of actin probably visualizes myofibrillary deterioration, which may correspond to reduced cardiac performance in a more direct manner than the histochemistry of apoptotic markers.

Three-year follow-up of patients with silent ischemia in the subacute phase of myocardial infarction after thrombolysis and early coronary intervention.

In order to assess the prognostic value of silent myocardial ischemia in acute myocardial infarction after thrombolysis and early coronary angiography (14-48 h after start of thrombolysis) including percutaneous transluminal coronary angioplasty, if indicated, 126 patients underwent 24 h-Holter-monitoring in the early postinfarction period. The 24 h-Holter-recording was initiated directly after early coronary intervention (40+/-11 h after onset of symptoms). Of the 126 patients initially eligible for the study 29 had to be excluded from further analysis for clinical or methodical reasons. Of the remaining 97 patients, 10 (10%) had silent ischemia (group A) and 87/97 (90%) patients showed no significant ST-segment alterations. Both groups did not significantly differ from each other with regard to baseline clinical characteristics, severity of coronary artery disease and frequency of successful percutaneous transluminal coronary angioplasty. The left ventricular ejection fraction showed a trend towards lower values in patients with than in those without silent ischemia (47+/-15% vs. 55+/-13%, p=0.07). When both silent ischemia and left ventricular ejection fraction <40% were present, a subset of patients at high risk for cardiac death could be identified (specificity: 98%, positive predictive accuracy: 75%). By Kaplan-Meier analysis, significantly more cardiac deaths occurred in group A than in group B (30% vs. 6%, p<0.01) during the three-year follow-up (950+/-392 days) after acute myocardial infarction. Regarding the cardiac events during long-term follow-up (emergency percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, non-fatal reinfarction, and cardiac death) there was no significant difference between both groups (30% vs. 18%, NS). In conclusion, Holter monitor-detected silent ischemia in the subacute phase of myocardial infarction after thrombolysis followed by early delayed coronary intervention occurs in 10% of the patients indicating either a residual ischemia in the infarcted zone despite a combined reperfusion strategy or a remote ischemic potential in case of multivessel disease. In this small selected group of infarct patients too, silent ischemia is to be considered as an important non-invasive parameter to predict cardiac death during long-term follow-up and provides valuable complementary information to left ventricular dysfunction, a well established prognostic marker in the postinfarction period.

[Coronary angiography and change in antioxidative status]. / Koronarangiographie und Veränderung des antioxidativen Status.

PATIENTS AND METHODS: In a prospective study in 53 patients with stable angina pectoris symptoms the antioxidant status (glutathione peroxidase, glutathione, superoxid dismutase, malondialdehyde and selenium in serum and whole blood) was determined before and 4 to 6 hours after coronary angiography. According to the results of the coronary angiography the patients were classified in a group with "severe" (n = 16) and another with "moderate" coronary alterations. RESULTS: In both groups there was a significant reduction of selenium in serum and whole blood. The enzymes glutathione peroxidase and superoxide dismutase as well as glutathione and malondialdehyde changed only slightly. CONCLUSION: These results can be the cause of an increase of the formation of free radicals during coronary reperfusion (PTCA, implantation of stents in the group with "severe" coronary alterations) but could also be seen as a sign of formation of radicals by the method itself (in patients with "moderate" coronary alterations). Further investigations are indicated. Furthermore the amelioration of the antioxidant status of the organism by scavenger substances (vitamins A, B, C and selenium) should be discussed.

Cardiac sympathetic activity as measured by myocardial 123-I-metaiodobenzylguanidine uptake and heart rate variability in idiopathic dilated cardiomyopathy.

In patients with idiopathic dilated cardiomyopathy (IDC) the increased sympathetic activity owing to chronic congestive heart failure leads to an imbalance of cardiac autonomic tone, as reflected by decreased heart rate variability (HRV). Iodine-123-metaiodobenzylguanidine (123-I-MIBG), which has the same affinity for sympathetic nerve endings as norepinephrine, can be used to assess the integrity and function of the cardiac sympathetic nervous system. The aim of the present study was to measure cardiac sympathetic activity by assessing 123-I-MIBG uptake compared with HRV in patients with IDC. In 12 patients with IDC and mild to moderate heart failure, myocardial MIBG uptake was calculated from the myocardial (M) to left ventricular cavity (C) voxel values density ratio and the 123-I activity in a blood sample as a reference (= M/C ratio) using a double radionuclide study with 123-I-MIBG and technetium-99m-MIBI. To investigate the relation between myocardial MIBG uptake and HRV in time domain, the linear regression between the M/C ratio, a new scintigraphic parameter, and the mean RR interval or the HRV triangular index, respectively, was determined. A significant correlation between the M/C ratio and mean RR interval (r = 0.52; p = 0.016) or M/C ratio and HRV triangular index (r = 0.76; p = 0.003), respectively, was found. Thus, the significant correlation between the M/C ratio and HRV indicate that they are both suitable noninvasive methods for evaluating cardiac sympathetic activity in patients with IDC and, furthermore, favor the view that there is evidence of a relation between HRV and the disorder of the cardiac presynaptic sympathetic nerve endings as demonstrated by a reduced M/C ratio.

Unexpanded, irretrievable stent in the proximal right coronary artery: successful management with stent graft implantation.

Stent loss and failure of retrieval are rare; nevertheless, complications have to be taken into account during percutaneous coronary intervention. Here we report a case of an unexpanded, irretrievable Palmaz-Schatz stent in the proximal right coronary artery near to the ostium and the successful management by implanting a synthetic stent graft.

Early time course of heart rate variability after thrombolytic and delayed interventional therapy for acute myocardial infarction.

In 89 of 97 consecutive patients with myocardial infarction (MI) undergoing thrombolysis and delayed early coronary angiography with PTCA, if indicated, heart rate variability (HRV) in time domain was evaluable 40 +/- 11 h after the onset of chest pain using 24-hour ECG recordings. Patients with anterior MI (n = 40) had lower values for HRV and left ventricular ejection fraction (p < 0.05). The mean of all 5-min standard deviations of RR intervals (SDNNi) and the root-mean-square difference of successive RR intervals (rMSSD) decreased significantly (p < 0.001 each), whereas the standard deviation of all normal RR intervals and the percentage of absolute differences between successive RR intervals only showed a tendency to lower values 4 weeks after MI (p = 0.20 and 0.08, respectively). The decreases in SDNNi and rMSSD were more evident in inferior than in anterior MI. The time course of HRV following MI was similar in patients with and without PTCA. These results indicate an initial vagal hyperactivity in inferior MI, which is quickly predominated by sympathetic activation and a prolonged recovery of the cardiac autonomic imbalance after MI despite a successful combined reperfusion therapy.

Vectorcardiographic monitoring to assess early vessel patency after reperfusion therapy for acute myocardial infarction.

Reperfusion therapy has lowered mortality in patients suffering from acute myocardial infarction. Failure to reperfuse is associated with an increased short- and long-term mortality. In a prospective study we used dynamic vectorcardiography to monitor 96 patients with acute myocardial infarction treated with reperfusion therapy to non-invasively assess coronary patency. The results from continuous monitoring were compared to those obtained from angiography. By using trend-analysis of QRS vector difference and ST vector magnitude, we were able to correctly identify 58 of the 70 patients (83%) with a reperfused infarct-related artery, and 19 of the 26 patients (73%) with a persistently occluded artery demonstrated at an early angiogram (diagnostic accuracy 80%). In patients with high-grade collateral flow to the infarct-related area, the results of the vectorcardiographic monitoring and of angiography showed the largest disagreement, whereas the accuracy of vectorcardiographic monitoring was high: 88% among patients without collaterals. The present results suggest that QRS complex and ST segment vectorcardiographic monitoring is a useful tool for assessing early coronary artery patency, and that dynamic vectorcardiography may help in identifying candidates for emergency coronary angiography.

Antibodies to human sinus node in sick sinus syndrome.

The incidence of autoantibodies against human conducting tissue was studied in 45 pacemaker patients with sick sinus syndrome (SSS), in 17 patients with bradyarrhythmia, and five patients with hypersensitive carotid sinus syndrome. Antibodies against the human sinus node were demonstrated in 29% of patients with SSS and in 24% of patients with bradyarrhythmia; a tenfold risk of SSS could be calculated in patients with this antibody as compared to age-matched controls. At least two subtypes of anti-sinus node antibodies were demonstrated: an antibody absorbable and another one not absorbable with ventricular myocardium. Patients with SSS and prior myocarditis of rheumatic fever have a threefold incidence of that antibody, demonstrating that anti-conducting tissue antibodies are etiologic indicators for former inflammatory heart disease. These antibodies may play a role in the secondary immunopathogenesis of sick sinus syndrome. This hypothesis emerges as an interesting new pathogenetic concept.