Transcatheter vs. surgical aortic valve replacement and medical treatment : Systematic review and meta-analysis of randomized and non-randomized trials.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has emerged as the procedure of choice for patients with severe aortic stenosis (AS) and high perioperative risk. We performed a meta-analysis to compare the mortality related to TAVR with medical therapy (MT) and surgical aortic valve replacement (SAVR). METHODS: A systematic literature search was conducted by two independent investigators from the database inception to 30 December 2014. Relative risk (RR) and odds ratio (OR) were calculated and graphically displayed in forest plots. We used I 2 for heterogeneity (meta-regression) and Egger's regression test of asymmetry (funnel plots). RESULTS: We included 24 studies (n = 19 observational studies; n = 5 randomized controlled trials), with a total of 7356 patients in this meta-analysis. Mean age had a substantial negative impact on the long-term survival of AS patients (OR = 1.544; 95% CI: 1.25-1.90). Compared with MT, TAVR showed a statistically significant benefit for all-cause mortality at 12 months (OR = 0.68; 95% CI: 0.49-0.95). Both TAVR and SAVR were associated with better outcomes compared with MT. TAVR showed lower all-cause mortality over SAVR at 12 months (OR = 0.81; 95% CI: 0.68-0.97). The comparison between SAVR and TAVR at 2 years revealed no significant difference (OR = 1.09; 95% CI: 1.01-1.17). CONCLUSION: In AS, both TAVR and SAVR provide a superior prognosis to MT and, therefore, MT is not the preferred treatment option for AS. Furthermore, our data show that TAVR is associated with lower mortality at 12 months compared with SAVR. Further studies are warranted to compare the long-term outcome of TAVR versus SAVR beyond a 2-year follow-up period.

Cardiovascular events and re-stenosis following administration of G-CSF in acute myocardial infarction: systematic review and meta-analysis.

BACKGROUND: Because of the recently published results of the MAGIC study there is confusion as to whether administration of granulocyte-colony stimulating factor (G-CSF) after acute myocardial infarction (MI) should be regarded as a potentially harmful treatment. This meta-analysis of appropriate clinical studies is intended to show the impact of G-CSF given after MI on aggravated incidence of coronary re-stenosis or progression of coronary lesions. METHODS: We used a fixed effects model based on the Mantel-Haenszel method to combine results from the different trials. These studies provided the basis for the current analysis comprising 106 patients of whom 62 were subjected to G-CSF treatment. RESULTS: Minimum lumen diameter (MLD) measured immediately after percutaneous coronary intervention (PCI) was similar in both groups with a diameter stenosis of 12.3% (SD 9.5%) in the G-CSF group and 10.3% (8.5%) in the control group (p = 0.32). At follow-up, both MLD and percentage stenosis were not different between G-CSF-treated and control patients. Subsequently, averaged late lumen loss revealed similar results and no differences between groups (p = 0.11), and neither stent thrombosis nor re-infarction in either group. CONCLUSIONS: The current meta-analysis of clinical reports fails to justify an elevated risk for coronary re-stenosis after PCI in acute MI or adverse events following G-CSF in the setting of MI when used after state of the art treatment in carefully conducted clinical protocols.

Apoptosis in patients with dilated cardiomyopathy and diabetes: a feature of diabetic cardiomyopathy?

BACKGROUND: Dilated cardiomyopathy (DCM) has been suggested to be a consequence of a prior viral infection leading to a chronic inflammatory and immunological reaction that leads to a structural and functional deterioration of the heart. Nevertheless, the results of present studies are conflicting, regarding the natural course of heart diseases associated with detection of viral genome and inflammation. On the other hand, diabetes mellitus (DM) is the leading endocrine disorder worldwide and sufficient to induce a cardiomyopathy. It is not known whether DM contributes to the clinical picture of cardiomyopathy associated with the presence of viral genome or inflammatory cells in the myocardium. Therefore, the present study was undertaken to compare histological, immunohistochemical, biochemical, and functional data as well as the outcome of patients presenting with DCM and positive for DM with patients negative for DM to evaluate for a diabetic contribution in the course of the disease. METHODS: A total of 216 patients were biopsied between January 1998 and April 2003. From 197 patients diagnosed as having DCM, we were able to complete data set regarding the presence of DM in 108 patients, 20 patients with and 88 patients without DM. RESULTS: There was no significant difference regarding age, gender, body mass index, presence of viral genome and inflammatory cells in the myocardium, left ventricular function and diameter, and the degree of heart insufficiency. There was a significant difference of apoptotic cells in the myocardium of patients with DCM and DM compared to patients with DCM alone (1.7+/-1.9 vs. 0.2+/-0.4, p=0.028). During the follow-up of 16 months, left ventricular function improved in both groups significantly, but not between the groups. Death or transplantation-free survival was not significantly different. CONCLUSION: The different findings regarding the presence of apoptotic cells suggest a contribution of pathobiological pathways in the patients with DM to the underlying heart disease.

[Intoxication with a tricyclic antidepressant]. / Intoxikation mit einem trizyklischen Antidepressivum.

A 48-year-old woman with a major depression and treatment with doxepin was found comatose in her flat. Her son last saw her 48 h prior to being found. On arrival of the emergency physician, she presented a generalized seizure. The patient underwent endotracheal intubation and mechanical ventilation due to respiratory insufficiency and severe cyanosis. Empty packages of tablets (doxepin ca. 4000 mg and zolpidem 100 mg) were found in the flat. On hospital admission the doxepin blood concentration was 1.2 microg/ml. No life-threatening arrhythmia occurred at any time. On the advice of the poison information center, hemoperfusion was performed for extracorporeal elimination. Within several hours the doxepin blood concentration could be lowered to 0.8 microg/ml and although still above the therapeutic range the patient was extubated. However, the patient developed a generalized seizure which required re-intubation. As a consequence of the high distribution volume and re-distribution phenomena, the doxepin blood concentration had increased again to 1.2 microg/ml. Approximately 72 h later she was extubated again while the doxepin blood concentration was 0.9 microg/ml and 3 days later, the doxepin blood concentration was lowered to 0.3 microg/ml and the patient was transferred to the psychiatric ward the following day. This case report questions the efficacy of hemoperfusion during acute doxepin intoxication in the given constellation of a non-life-threatening arrhythmia.

Treatment with granulocyte-colony stimulating factor in patients with acute myocardial infarction. Evidence for a stimulation of neovascularization and improvement of myocardial perfusion.

BACKGROUND: Stem cell therapy has been suggested to be beneficial in patients after acute myocardial infarction (AMI). Strategies of treatment are either a local application of mononuclear bone marrow cells (BMCs) into the infarct-related artery or a systemic therapy with the granulocyte-stimulating factor (G-CSF) to mobilize BMCs. Nevertheless, the mechanisms responsible for improvement of cardiac function and perfusion are speculative at present. This study has been performed to investigate the effect of G-CSF on systemic levels of vascular growth factors and chemokines responsible for neovascularization, that might help to understand the positive effects of a G-CSF therapy after AMI. METHODS AND RESULTS: Five patients in the treatment group and 5 patients in the control group were enrolled in this study. The patients in the treatment group received 10 microg/kg bodyweight/day of G-CSF subcutaneously for a mean treatment duration of 6.6 +/- 1.1 days. In both groups, levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and monocyte chemotactic protein-1 (MCP-1) were measured on day 2 to 3 and day 5 after AMI. The regional wall perfusion and the ejection fraction (EF) were evaluated before discharge and after 3 months with ECG-gated MIBI-SPECT and radionuclide ventriculography, respectively. Significant higher levels of VEGF (p < 0.01), bFGF (p < 0.05) and MCP-1 (p < 0.05) were found in the treatment group compared to the control group. Levels of VEGF and bFGF remained on a plateau during the G-CSF treatment and decreased significantly in the control group. The wall perfusion improved significantly within the treatment group and between the groups (p < 0.05), respectively. The EF improved significantly within the treatment group (p < 0.05), but the change of the EF between the groups was not significant. CONCLUSION: In patients with AMI, the treatment with G-CSF modulates the formation of vascular growth factors that might improve neovascularization and result in an improved myocardial perfusion and function.

Creatine supplementation improves muscle strength in patients with congestive heart failure.

BACKGROUND: Both, cardiac and skeletal muscle creatine levels are depressed in patients with congestive heart failure (CHF). Oral supplementation of creatine (Cr) could increase physical performance in healthy volunteers. We therefore hypothesized that oral creatine supplementation improves skeletal muscle strength, quality of live and symptom-limited performance in patients with CHF. METHODS: In a double-blind, placebo-controlled and crossover-designed study, 20 patients suffering from congestive heart failure more than 6 months and a peak oxygen uptake (peak VO2) below 20 ml/min/kg received 4 x 5 g Cr daily vs. placebo for 6 weeks and were crossed over for the following 6 weeks. Peak VO2, VO2 at the anaerobic threshold (VO2AT), ejection fraction (EF), distance in 6-minute-walk-test (6 min W), and muscle strength (Modified Sphygmomanometer (MS)) were determined at baseline, after 6, and after 12 weeks. Dyspnoea after 6-minute-walk-test was measured using the Borg Scale. Quality of live was assessed with the Minnesota Living with Heart Failure Questionnaire (MLHFQ). RESULTS: 13 of 20 Patients finished the study. After 6 weeks of creatine supplementation there was a significant increase in body weight and muscle strength compared to baseline and placebo (p < 0.05). However, there was no significant change in peak VO2, VO2AT, walking distance, quality of life assessment and EF. CONCLUSION: Short-term creatine supplementation inaddition to standard medication in patients with CHF leads to an increase in body weight and an improvement of muscle strength. This effect is restricted to the time of supplementation.

[Mobilization of stem cells by granulocyte colony-stimulating factor for the regeneration of myocardial tissue after myocardial infarction]. / Mobilisation von Stammzellen durch den Granulozyten-Kolonie stimulierenden Faktor zur Regeneration myokardialen Gewebes nach Herzinfarkt.

BACKGROUND AND OBJECTIVE: Animal data suggest that mobilized bone marrow cells (BMC) may contribute to tissue regeneration after myocardial infarction (MI). However the safety, feasibility and efficacy of treatment with granulocyte colony-stimulating factor (G-CSF) to mobilize BMC after acute myocardial infarction in patients is unknown. We analysed cardiac function and perfusion in 5 patients who were treated with G-CSF in addition to standard therapeutical regimen. METHODS AND RESULTS: 48 h after successful recanalization and stent implantation in 5 patients with acute MI, the patients received 10 micro g/kg bodyweight/day G-CSF subcutaneously for a mean treatment duration of 7.6+/-0.5 days. Peak value of CD34 (+) cells, a multipotent subfraction of bone marrow cells, was reached after 5.0+/-0.7 days. After 3 months of follow-up global left ventricular ejection fraction (determined by radionuclid-ventriculography) increased significantly from 42.2+/-6.6 % to 51.6+/-8.3 % (P<0.05). The wall motion score and the wall perfusion score (determined by ECG gated SPECT) decreased from 13.5+/-3.6 to 9.9+/-3.5 (P<0.05) and from 9.6+/-2.9 to 7.0+/-4.5 (P<0.05), respectively, indicating a significant improvement of myocardial function and perfusion. No severe side effects of G-CSF treatment could be observed. Malignant arrhythmias were not observed either. CONCLUSION: In patients with acute MI, treatment with G-CSF to mobilize BMC appears to be well tolerable under clinical conditions. Improved cardiac function and perfusion may be attributed to BMC-associated promotion of myocardial regeneration and neovascularization.