Prediction of heart failure and death in an adult population of Fontan patients.

BACKGROUND: Late Fontan survivors are at high risk to experience heart failure and death. Therefore, the current study sought to investigate the role of non-invasive diagnostics as prognostic markers for failure of the systemic ventricle following Fontan procedure. METHODS: This monocentric, longitudinal observational study included 60 patients with a median age of 24.5 (19-29) years, who were subjected to cardiac magnetic resonance imaging, echocardiography, cardiopulmonary exercise testing, and blood analysis. The primary endpoint of this study was decompensated heart failure with symptoms at rest, peripheral and/or pulmonary edema, and/or death. RESULTS: During a follow-up of 24 months, 5 patients died and 5 patients suffered from decompensated heart failure. Clinical (NYHA class, initial surgery), functional (VO2 peak, ejection fraction, cardiac index), circulating biomarkers (N-terminal pro brain natriuretic peptide), and imaging parameters (end diastolic volume index, end systolic volume index, mass-index, contractility, afterload) were significantly related to the primary endpoint. Multi-variate regression analysis identified afterload as assessed by cardiac magnetic resonance imaging as an independent predictor of the primary endpoint (hazard ratio 1.98, 95% confidence interval 1.19-3.29, p = 0.009). CONCLUSION: We identified distinct parameters of cardiopulmonary exercise testing, cardiac magnetic resonance imaging, and blood testing as markers for future decompensated heart failure and death in patients with Fontan circulation. Importantly, our data also identify increased afterload as an independent predictor for increased morbidity and mortality. This parameter is easy to assess by non-invasive cardiac magnetic resonance imaging. Its modulation may represent a potential therapeutic approach target in these high-risk patients.

Diagnostic evaluation of the hospital depression scale (HADS) and the Beck depression inventory II (BDI-II) in adults with congenital heart disease using a structured clinical interview: Impact of depression severity.

OBJECTIVE: The purpose of this study was the diagnostic evaluation of the hospital anxiety and depression scale total score, its depression subscale and the Beck depression inventory II in adults with congenital heart disease. METHODS: This cross-sectional study evaluated 206 patients with congenital heart disease (mean age 35.3 ± 11.7 years; 58.3% men). Major depressive disorder was diagnosed by a structured clinical interview for the Diagnostic and Statistical Manual of Mental Disorders IV and disease severity with the Montgomery-Åsberg depression rating scale. Receiver operating characteristics provided assessment of diagnostic accuracy. Youden's J statistic identified optimal cut-off points. RESULTS: Fifty-three participants (25.7%) presented with major depressive disorder. Of these, 28 (52.8%) had mild and 25 (47.2%) had moderate to severe symptoms. In the total cohort, the optimal cut-off of values was >11 in the Beck depression inventory II, >11 in the hospital anxiety and depression scale and >5 in the depression subscale. Optimal cut-off points for moderate to severe major depressive disorder were similar. The cut-offs for mild major depressive disorder were lower (Beck depression inventory II >4; hospital anxiety and depression scale >8; >2 in its depression subscale). In the total cohort the calculated area under the curve varied between 0.906 (hospital anxiety and depression scale) and 0.93 (Beck depression inventory II). Detection of moderate to severe major depressive disorder (area under the curve 0.965-0.98) was excellent; detection of mild major depressive disorder (area under the curve 0.851-0.885) was limited. Patients with major depressive disorder had a significantly lower quality of life, even when they had mild symptoms. CONCLUSION: All scales were excellent for detecting moderate to severe major depressive disorder. Classification of mild major depressive disorder, representing 50% of cases, was limited. Therapy necessitating loss of quality of life is already present in major depressive disorder with mild symptoms. Established cut-off points may still be too high to identify patients with major depressive disorder requiring therapy. External validation is needed to confirm our data.

Mortality in Patients With Out-of-Hospital Cardiac Arrest Undergoing a Standardized Protocol Including Therapeutic Hypothermia and Routine Coronary Angiography: Experience From the HACORE Registry.

OBJECTIVES: This study sought to analyze the impact of mandatory therapeutic hypothermia and cardiac catheterization in the absence of overt noncardiac cause of arrest as part of the Hannover Cardiac Resuscitation Algorithm before intensive care admission. BACKGROUND: Despite advanced therapies, out-of-hospital cardiac arrest (OHCA) is still associated with high mortality rates. Recently, the TTM (Target Temperature Management 33°C Versus 36°C After Out-of-Hospital Cardiac Arrest)-trial caused severe uncertainty about the efficacy of and need for therapeutic hypothermia. Furthermore, the role of early coronary angiography in OHCA survivors without ST-segment elevation remains undetermined. METHODS: In the HACORE (HAnnover Cooling REgistry) we investigated 233 consecutive patients (median age 64 [interquartile range: 53 to 74] years) with OHCA admitted to our institution between January 2011 and December 2015 who were treated according to the algorithm. RESULTS: A total of 73% had ventricular fibrillation as primary rhythm. Return of spontaneous circulation was achieved after 20 (interquartile range: 10 to 30) min. Immediate percutaneous coronary angiography was performed in 96% and coronary angioplasty in 59% of all cases. ST-segment elevation was present in 47%. Critical coronary stenosis requiring percutaneous coronary intervention was present in 67% of patients with and 52% of patients without ST-segment elevation. Overall 30-day intrahospital mortality in this real-world registry was 37%. Patients in our local registry who matched the inclusion/exclusion criteria of the TTM-trial (n = 145) had a markedly lower 30-day mortality (27%) compared with the published trial (44%). CONCLUSIONS: Standardized treatment of patients with OHCA following a strict protocol incorporating computed tomography, cardiac catheterization and revascularization, liberal use of active hemodynamic support in presence of shock, and mandatory therapeutic hypothermia results in mortality rates lower than previously reported.

Leukocytoclastic vasculitis associated with endocarditis in a patient with transposition of the great arteries and mechanical valve replacement.

Immunological vascular phenomena can be the initial manifestation of bacterial infection and endocarditis. Here, we report a rare case of leukocytoclastic vasculitis without immune complexes or cryoglobulinemia in a patient with infective endocarditis, congenital heart disease, and a prior mechanical valve replacement. The patient completely recovered following antibiotic therapy, and skin lesions disappeared without immune suppression, which suggested infection-mediated vasculitis. While the treatment of leukocytoclastic vasculitis typically involves immunosuppressive therapy, the treatment for infection-mediated vasculitis is eradication of the infection.

[Pseudoaneuryma after transradial puncture in systemic lysis of basilar artery thrombosis]. / Pseudoaneurysma nach transradialer Punktion bei systemischer Lyse einer Basilaristhrombose.

HISTORY: Because of neurological symptoms as a result of thrombotic occlusion of the basilar artery, a successful revascularization after systemic Actilyse application was performed in a 78 year old patient. Later, it came to the formation of a pseudoaneurysm at the radial artery, punctured for invasive blood pressure measurement. TREATMENT AND COURSE: After oscillographic respectively ultrasound detection of a 2 cm wide pseudoaneurysm from the radial artery, the surgical resection of the aneurysm sac was performed. An ultrasound-guided manual compression due to the localization of a thrombus close to the aneurysm neck could not be conducted. The further clinical course was unremarkable. CONCLUSION: With an increasing number of pseudoaneurysms as a complication of transradial puncture occuring more frequently in the context of intensive care supply and rising outpatient cardiac catheterization (coronary angiography and PCI), the knowledge of care options of vascular complications are of particular importance before practical application.

NT-proBNP Indicates Left Ventricular Impairment and Adverse Clinical Outcome in Patients With Tetralogy of Fallot and Pulmonary Regurgitation.

BACKGROUND: The goal of this study was to interrelate N-terminal B-type natriuretic peptide (NT-proBNP) levels and cardiac magnetic resonance imaging-derived ventricular function, mass, and volumes in adults with pulmonary regurgitation after Fallot repair and to evaluate the prognostic relevance of these parameters regarding adverse clinical outcome. METHODS: Eighty-one patients (aged 26.3 ± 7.4 years; male sex, 45.7%; New York Heart Association class I, 72.8%; pulmonary valve velocity, < 3 m/s) were included. At baseline cardiac magnetic resonance imaging and NT-proBNP measurements were performed. RESULTS: During a mean observation time of 6.9 ± 2.6 years, 13 patients (16.1%) had sustained supraventricular arrhythmias or heart failure (2.4 per 100 patient-years). Multivariate Cox analysis identified NT-proBNP, left ventricular (LV) end-systolic volume index and LV ejection fraction, right ventricular (RV) end-diastolic volume index, and tricuspid regurgitation as independent predictors of adverse events. NT-proBNP correlated with LV but not with RV parameters. In receiver operating characteristic curve analysis using significant variables of the multivariate analysis, NT-proBNP was superior to all other parameters to detect patients at risk (area under the curve [AUC], 0.873; 95% confidence interval, 0.772-0.974). LV end-systolic volume index (AUC, 0.734), RV end-diastolic volume index (AUC, 0.645) und tricuspid regurgitation (AUC, 0.747) showed lower diagnostic accuracy. CONCLUSIONS: Even in mildly symptomatic patients with pulmonary regurgitation after Fallot repair NT-proBNP is a strong predictor of adverse outcome. It is rather associated with LV but not with RV impairment. In severe pulmonary regurgitation an increase in the level of NT-proBNP and LV impairment seem to provide additional useful information for the timing of pulmonary valve replacement.

Adenoviral expression of a transforming growth factor-beta1 antisense mRNA is effective in preventing liver fibrosis in bile-duct ligated rats.

BACKGROUND: Transforming growth factor-beta (TGF-beta) is a key mediator in establishing liver fibrosis. Therefore, TGF-beta as a causative agent may serve as a primary target for antifibrotic gene therapy approaches. We have previously shown that the adenoviral delivery of a transgene constitutively expressing a TGF-beta1 antisense mRNA blocks TGF-beta synthesis in culture-activated hepatic stellate cells and effectively abolishes ongoing fibrogenesis in vitro. METHODS: Ligature of the common bile duct was used to induce liver fibrosis in rats. The effect of the TGF-beta1 antisense on fibrogenesis was analyzed in this model of liver injury. RESULTS: In the present study, we demonstrate that the adenoviral vector directs the synthesis of mRNA quantities that are approximately 8000-fold more abundant than endogenous TGF-beta1 mRNA. In experimentally injured rat livers induced by ligature of the common bile duct, a model for persistent fibrogenesis and cirrhosis, administration of the adenoviral vector abrogates TGF-beta-enhanced production of collagen and alpha-smooth muscle actin. Furthermore, the number of cells positive for alpha-smooth muscle actin resulting from active recruitment of activated hepatic stellate cells around the bile ductular structures was significantly reduced in animals after application of Ad5-CMV-AS-TGF-beta1. However, the observed elevated serum levels of aspartate aminotransferase, alanine aminotransferase, and bilirubin induced in this obstructive liver injury model were not significantly altered in the presence of the TGF-beta antagonist. CONCLUSION: Taken together, our data provides in vivo evidence that the delivery of TGF-beta1 antisense mRNA specifically abolishes the diverse effects of direct TGF-beta function in ongoing liver fibrogenesis. Therefore, we conclude that the expressed transgene is therapeutically useful for inhibition of TGF-beta effects in diverse applications, ranging from clarification of TGF-beta function in the course of liver injury to the development of novel gene therapeutic approaches.

Dominant-negative soluble PDGF-beta receptor inhibits hepatic stellate cell activation and attenuates liver fibrosis.

Hepatic fibrogenesis is a consequence of hepatic stellate cells that become activated and transdifferentiate into a myofibroblastic phenotype with the ability to proliferate and synthesize large quantities of extracellular matrix components. In this process, platelet-derived growth factor (PDGF) is the most potent stimulus for hepatic stellate cell proliferation and migration, and is overexpressed during active hepatic fibrogenesis. This cytokine binds to the PDGF receptor type beta, activates Ras and sequentially propagates the stimulatory signal sequentially via phosphorylation of Raf-1, MEK and the extracellular-signal regulated kinases ERK1/ERK2. Hepatic injury is associated with both increased autocrine PDGF signaling and upregulation of PDGF receptor. In this study, we report that a dominant-negative soluble PDGF-beta receptor consisting of a chimeric IgG containing the extracellular portion of the PDGF receptor type beta blocks HSC activation and attenuates fibrogenesis induced by ligation of the common bile duct in rats. In culture-activated hepatic stellate cells, the soluble receptor blocks phosphorylation of endogenous PDGF receptor, phosphorylation of the ERK1/EKR2 signal and reduces proliferative activities of HSC. In vivo, both the delivery of the purified soluble PDGF antagonist and the administration of adenoviruses expressing the artificial transgene were able to reduce significantly the expression of collagen and alpha-smooth muscle actin. Our results demonstrate that PDGF plays a critical role in the progression and initiation of experimental liver fibrogenesis, and suggest that early anti-PDGF intervention should have a therapeutical impact on the treatment of liver fibrogenesis.