Renal denervation with standard radiofrequency ablation catheter is effective in 24-hour ambulatory blood pressure reduction - follow-up at 1/3/6/12 months.

AIMS: To examine the effect of renal denervation (RDN) on 24­h ambulatory blood pressure (ABP) with a standard radiofrequency ablation catheter (RF catheter). METHODS: Seventy-five patients with resistant hypertension received bilateral RDN with an RF catheter (6 RF applications, 1 minute each, 8-12 watts). Seventy patients fulfilled inclusion criteria with mean systolic ABP ≥140 mmHg (mean 165/89) despite treatment with ≥3 antihypertensive drugs (mean 5.9) including a diuretic, and were further analysed for ABP changes. Follow-up at 1/3/6/12 months comprised biochemical evaluations and ABP measurement. At 6/12 months, duplex sonography of the renal arteries was additionally performed. RESULTS: At 1/3/6/12 months we observed a significant reduction in systolic ABP of -15/-17/-18/-15 mmHg (n = 55/53/57/50; non-parametric Friedman test, p < 0.001) and diastolic ABP of -6/-9/-10/-7 mmHg (p < 0.001). Of the patients, 70 %/64 % showed a systolic ABP reduction of ≥10 mmHg, and 77 %/70 % of ≥5 mmHg at 6/12-month follow-up. Two patients (2.7 %) developed renal artery stenosis (>70 %) with subsequent stenting without complications. Logistic regression analysis with systolic ABP reduction ≥10 mmHg at 12 months follow-up as criterion revealed that only the mean baseline systolic ABP was significant, OR = 2.174. CONCLUSIONS: RDN with a standard RF catheter can be used safely to reduce mean ABP in resistant hypertension as shown in long-term follow-up.

[Interventions at the tricuspid valve: What is possible?]. / Trikuspidalklappeninterventionen : Was ist machbar?

Due to the increased life expectancy and continual improvements in cardiological treatment options, diseases of the tricuspid valve, in particular tricuspid valve insufficiency will become increasingly more recognized as an interventional target. While tricuspid stenosis is rare and can be effectively treated with balloon valvuloplasty, no effective transcatheter approach to tricuspid regurgitation (TR) has yet been established. As the tricuspid annulus is a complex and highly dynamic structure that offers little resistance, orthotopic long-term fixation of transcatheter valves with the current techniques is challenging and has not yet been performed in human patients. Alternative treatment concepts include transcatheter caval valve implantation (CAVI) to address the regurgitation of blood into the caval veins, which has resulted in hemodynamic improvement and is currently undergoing further clinical investigation. Other interventional treatment concepts are aimed at tricuspid valve repair, e.g. by annular plication with the Mitralign™ device or the TriCinch™ system. In the medium-term it can be assumed that percutaneous systems and therapy options will become available for these indications whereby the functional and prognostic effects of these treatment procedures will be corroborated in the appropriate patient groups by corresponding studies.

[Interventional therapy of heart valve diseases: future perspectives]. / Interventionelle Therapie von Herzklappenerkrankungen : Ein Ausblick.

Transcatheter procedures have been adopted as novel treatment strategy for patients with valvular heart disease, particularly for those who are inoperable or at high risk for surgical valve procedures. Significant technological advances have resulted in an improvement of devices for transcatheter aortic valve replacement (TAVI) with downsizing of crossing profiles, reduction in the rate of paravalvular leakage and conduction abnormalities as well as a lower short- and mid-term mortality and a higher patient acceptance. In the near future, TAVI may potentially develop as first-line treatment for the majority of patients with aortic valve disease. For patients with mitral and pulmonary stenosis, balloon valvuloplasty is effective and well established and should be preferred over valve replacement, last but not least also for economic reasons. For treatment of mitral regurgitation, several transcatheter devices aiming to restore or replace mitral valve function are currently under investigation. This review summarizes the current state of interventional treatment of valvular heart disease along with implications for the future.

QT variability improves risk stratification in patients with dilated cardiomyopathy.

Recently it could be demonstrated that systolic and diastolic blood pressure variability (BPV) as well as segmented Poincare plot analysis (SPPA) contribute to risk stratification in patients suffering from dilated cardiomyopathy (DCM). The aim of this study was to improve the risk stratification applying a multivariate technique including QT variability (QTV). We enrolled and significantly separated 56 low risk and 13 high risk DCM patients by nearly all applied BPV and QTV methods, but not with traditional heart rate variability analysis. The optimum set of two indices calculating the multivariate discriminate analysis (DA) included one BPV index calculated by symbolic dynamics method (DBP(Shannon)) and one index calculated from QTV (QTV(log)) achieving an area under the receiver operating characteristics curve (AUC) of 92%, sensitivity of 92.3% and specificity of 89.3%. Performing only electrocardiogram analysis, the optimum multivariate approach including indices from segmented Poincaré plot analysis and QTV still achieved a remarkable AUC of 88.3%. Increasing the number of indices for multivariate DA up to three, we achieved an AUC of 95.7%, sensitivity of 100% and specificity of 85.7% including one clinical, one BPV and one QTV index. Summarizing, we identified DCM patients with an increased risk of sudden cardiac death applying QTV analysis in a multivariate approach.

Hypothermia after cardiac arrest does not affect serum levels of neuron-specific enolase and protein S-100b.

BACKGROUND: We investigated the brain-derived proteins neuron-specific enolase (NSE) and protein S-100b (S-100b) in survivors of cardiac arrest who had either received therapeutic hypothermia (TH) or had not. METHODS: In a retrospective cohort study, we analysed serum levels of these two proteins over 5 days in 201 adult cardiac arrest survivors admitted to our intensive care unit between 2003 and 2010. These were all survivors that remained comatose and survived at least 48 h. Of these, 140 received therapeutic hypothermia (hypothermia group). The remainder received only standard therapy without hypothermia (normothermia group). RESULTS: There was no difference in survival between the hypothermia and normothermia groups. At 4 weeks after arrest, 61 (43.6%) patients of the hypothermia group and 26 (42.6%) patients of the normothermia group were still alive with favourable to moderate neurological outcome (Cerebral Performance Category Scale 1-3). We observed no change in the mean serum levels of either protein between the two groups. Within each group, we found significantly higher serum levels of NSE and S-100b in patients with unfavourable neurological outcome (Cerebral Performance Category Scale 4 and 5) than in those with moderate to favourable outcome. Cut-off levels 3 days after cardiac arrest predicting an unfavourable outcome were >40 ng/ml for NSE [specificity 95.2%, Sensitivity 74.1%, areas under the curve (AUC):0.889], false positive rate 4 [confidence interval (CI): 0.0131-0.1175] and >1.03 µg/1 for S-100b (specificity 95.6%, Sensitivity 57.8%, AUC: 0.875) false positive rate 3 (CI: 0.0091-01218). CONCLUSIONS: Additional application of TH was not associated with significant changes in serum levels of NSE and S-100b in comatose survivors of cardiac arrest, compared to those treated without TH.

Altered red blood cell distribution width in overweight adolescents and its association with markers of inflammation.

BACKGROUND: Obesity and the metabolic syndrome are dramatically increasing problems. Red blood cell distribution width (RDW), the variability in size of circulating red blood cells, has been demonstrated to be altered in different clinical settings. This analysis aimed to investigate the relationship between RDW and obesity in adolescents and in an animal model of diet-induced obesity (DIO). METHODS: Seventy-nine male adolescents (aged 13-17 years) were studied. Thirty-seven of them were overweight (body mass index ≥ 90th percentile). RDW, markers of inflammation and stem cell factor (SCF) were determined. In an animal study, mice were fed with different diets for 15 weeks. RDW was determined using an animal blood count machine. RESULTS: RDW differed significantly between normal-weight adolescents (13.07 ± 0.09) and overweight adolescents (13.39 ± 0.10, P = 0.015), whereas erythrocyte counts and haematocrit did not differ. RDW correlated to markers of inflammation and inversely to SCF. In the mice animal model, nutritional changes increased RDW, whereas overweight per se did not change RDW. CONCLUSIONS: RDW is elevated in overweight and reflects the inflammatory state. RDW potentially represents an additional and cost-effective tool to indicate inflammation. Future studies are needed to understand the differential influences of nutrition and overweight on RDW.

The German Aortic Valve Registry (GARY): a nationwide registry for patients undergoing invasive therapy for severe aortic valve stenosis.

Background The increasing prevalence of severe aortic valve defects correlates with the increase of life expectancy. For decades, surgical aortic valve replacement (AVR), under the use of extracorporeal circulation, has been the gold standard for treatment of severe aortic valve diseases. In Germany ~12,000 patients receive isolated aortic valve surgery per year. For some time, percutaneous balloon valvuloplasty has been used as a palliative therapeutic option for very few patients. Currently, alternatives for the established surgical procedures such as transcatheter aortic valve implantation (TAVI) have become available, but there are only limited data from randomized studies or low-volume registries concerning long-time outcome. In Germany, the implementation of this new technology into hospital care increased rapidly in the past few years. Therefore, the German Aortic Valve Registry (GARY) was founded in July 2010 including all available therapeutic options and providing data from a large quantity of patients.Methods The GARY is assembled as a complete survey for all invasive therapies in patients with relevant aortic valve diseases. It evaluates the new therapeutic options and compares them to surgical AVR. The model for data acquisition is based on three data sources: source I, the mandatory German database for external performance measurement; source II, a specific registry dataset; and source III, a follow-up data sheet (generated by phone interview). Various procedures will be compared concerning observed complications, mortality, and quality of life up to 5 years after the initial procedure. Furthermore, the registry will enable a compilation of evidence-based indication criteria and, in addition, also a comparison of all approved operative procedures, such as Ross or David procedures, and the use of different mechanical or biological aortic valve prostheses.Results Since the launch of data acquisition in July 2010, almost all institutions performing aortic valve procedures in Germany joined the registry. By now, 91 sites which perform TAVI in Germany participate and more than 15,000 datasets are already in the registry.Conclusion The implementation of new or innovative medical therapies needs supervision under the conditions of a well-structured scientific project. Up to now relevant data for implementation of TAVI and long-term results are missing. In contrast to randomized controlled trials, GARY is a prospective, controlled, 5-year observational multicenter registry, and a real world investigation with only one exclusion criterion, the absence of patients' written consent.

[Incessant or recurrent ventricular tachycardia. Indications for emergency ablation]. / Unaufhörliche oder rezidivierende ventrikuläre Tachykardien. Wann ist die Notfallablation indiziert?

Incessant ventricular tachycardia and "electrical storms" are emergencies, requiring urgent action in a close cooperation between critical care physicians and cardiologists. The leading cause of such events is advanced cardiac disease. Besides the patient's history, an ECG and, if applicable, an implantable cardioverter-defibrillator (ICD) interrogation is required for a reliable diagnosis. Further diagnostics include laboratory parameters, an echocardiogram, and possibly a coronary angiography. The medical therapy, consisting of amiodarone and ß-blockers, should immediately be initiated after diagnosis. In the case of failed drug therapy, urgent catheter ablation is indicated. This is a complex procedure, in which the clinical tachycardia or the electrical substrate is modified by using an irrigated catheter. The acute success rate of this life-saving procedure is high. However, there might also be complications due to the required extensive procedures.

Smelling heart failure from human skin odor with an electronic nose.

The human body odor contains different volatile organic compounds which can be used as biomarkers for various diseases. The early detection of heart failure (HF) through periodical screening provides an early treatment application. Therefore we have developed a completely new non-invasive method to identify HF applying an "electronic nose" (e-nose) which provides a "smelling" of the disease based on the analysis of sweat volatile gases from the skin surface. For this e-nose a special applicator carrying the sensor chip was developed which can be applied directly on the skin surface. 27 patients with decompensated HF (DHF), 25 patients with compensated HF (CHF, mean age 70.72 ± 12.02) and 28 controls (CON) were enrolled in this first pilot study.

[Evaluation of microcirculatory disorders in shock patients]. / Diagnostik von Mikrozirkulationsstörungen bei Schockpatienten.

The microcirculatory status depicts an indicator of organ perfusion in hemodynamic shock. Distribution pattern of microcirculatory disturbances reflects the underlying cause of shock: In septic shock, organ perfusion is severely impaired via arteriolo-venous shunting with shutting up small vessel perfusion; however, cardiogenic shock is characterized by a global impairment of microcirculation, involving all vascular beds. Hence, a differentiated evaluation of microcirculatory disturbances not only supports an early diagnosis of an imminent multiorgan dysfunction syndrome (MODS), but also allows a more accurate evaluation of severity of hemodynamic compromise in critical care medicine. Bedside sidestream darkfield (SDF) technique offers the opportunity to describe the microcirculatory status quo semiquantitatively and to evaluate the effect of novel therapeutic approaches on microcirculation. Further technical improvements of this technique may open new fields of diagnostic and therapeutic applications in intensive care medicine by supporting an early diagnosing of MODS, evaluating prognosis, and optimizing therapeutic measures .

Autonomic regulation during mild therapeutic hypothermia in cardiopulmonary resuscitated patients.

OBJECTIVE: We investigated whether there are differences in autonomic cardiovascular regulation in resuscitated patients undergoing therapeutic hypothermia (TH) in relation to the clinical outcome. METHOD: Between 2005 and 2007, 18 consecutive resuscitated patients were enrolled. ECG and blood pressure data were recorded for 48 h during hypothermia and warming up to a body core temperature of 36°C. Autonomic regulation was assessed by applying time, frequency, and non-linear dynamics domain methods from heart rate and blood pressure variability (HRV/BPV) analyses. RESULTS: Nine patients survived with good neurological recovery, and nine patients died during the ICU stay. In both groups, we found a decreased HRV presented by standard deviation of R-R intervals (sdNN) below 50 ms(2) at each time of measurement. Immediately after recovery to a body core temperature of 36°C, a significant higher HRV was found in survivors compared to non-survivors by means of indices sdNN (40.2 ± 19.5 vs. 10.9 ± 4.1 ms(2), P = 0.01), R-R intervals distribution histogram [shannon] (3.7 ± 0.6 vs. 2.2 ± 0.4, P = 0.008), very low frequency band [VLF] (152.2 ± 99.3 vs. 3.4 ± 1.9, P = 0.001) and the variance of the time series of R-R intervals [Wsdvar] (1.16 ± 0.52 vs. 0.29 ± 0.25, P = 0.02) . A decreased spontaneous BPV was found only among survivors comparing blood pressure characteristics within stable hypothermia to the initial state before hypothermia. CONCLUSION: Resuscitated patients show a significantly reduced HRV before, during and after TH. Compared to survivors, the non-survivors show a further and significantly decrease of HRV immediately after hypothermia.

[Transcatheter aortic-valve implantation for aortic stenosis. An established procedure?]. / Kathetergeführte Aortenklappenimplantation. Ein etabliertes Verfahren?

Western countries are facing a huge increase of hemodynamically relevant cases of aortic stenosis in an aging population. In the past, about 33% of patients with symptomatic aortic stenosis were not referred for aortic valve replacement although the three years survival rate is only 25 percent after conservative treatment. In Germany transcatheter aortic-valve implantations (TAVI) procedures are reimbursed according to a DRG number. Its usage its not only regulated in a position paper of the German Society of Cardiology giving detailed recommendations for its application and indication. In Germany, approximately 4.000 TAVI procedures were performed in 2009 and even more are expected in 2010. According to the frequency of its usage, DRG reimbursement, and position papers, TAVI procedures seem to be established. However, according to health regulations a new treatment modality is only established if its safety and efficiency is proven, if there is a demand, and if the procedure has economic advantages. According to this definition TAVI is not established since its safety and efficiency compared to the surgical treatment was not been proven in randomised trials yet. Its economic burden in this context is unclear, too. However, there is a need for an alternative to surgical aortic valve replacement to increase the acceptance of valve implantation in an aging population.

Transcatheter aortic valve implantation: evidence on safety and efficacy compared with medical therapy. A systematic review of current literature.

OBJECTIVES: Transcatheter aortic valve implantation (TAVI) promises effective treatment for high-risk elderly patients with symptomatic severe aortic stenosis (AS). However, the adoption of TAVI must be justified and guarantee long-term performance. Systematic reviews are a core methodology in evidence-based health economics for judging medical effectiveness. In this work, the methodology was applied to provide objective evidence on the efficacy and safety of TAVI at 1-year follow-up and to assess whether TAVI confers a survival benefit compared with medical therapy. METHODS: In accordance with the toolkit of the "German Scientific Working Group Technology Assessment for Health Care" (GSWG), a systematic literature review on the safety and efficacy of TAVI procedures was conducted in major bibliographic databases to identify all relevant publications. Preestablished inclusion criteria were defined. An initial screening of identified articles regarding titles and abstracts was followed by a full-text screening. Data from eligible articles were extracted and evaluated according to GSWG checklists followed by a qualitative synthesis of information. RESULTS: The systematic literature search identified 12 primary publications (derived from 1,849 citations) for TAVI [number of patients (n) = 1,049] and 11 publications (derived from 189 citations) for medical therapy of AS (n = 946) that fulfilled the inclusion criteria. Mean overall procedural success rate for included TAVI interventions was 93.3%. Mean combined procedural, post-procedural, and cumulative in-hospital/30-day mortality was 11.4% (n = 116; range 5.3-23%). 1 year after TAVI, the mean overall survival rate was 75.9% (range 64.1-87%) compared with 62.4% (range 40-84.8%) for medically treated patients (p value < 0.01). 1-year survival after TAVI for patients treated with transvascular (TV) procedures was higher than after transapical (TA) procedures (79.2 vs. 73.6%) (p value = 0.04). At 1-year follow-up, the improved valvular function remained stable, and there was a trend towards an improved ventricular function. CONCLUSION: Based on the best available data, in patients with symptomatic severe AS, TAVI demonstrates an improved 1-year survival compared with medical treatment. The survival benefit of TV-TAVI over medical therapy elucidated from this systematic literature review is +16.8% and therefore, in good congruence with the recently published results from the randomized PARTNER US trial (+20%).

Extra cellular matrix remodelling after heterotopic rat heart transplantation: gene expression profiling and involvement of ED-A+ fibronectin, alpha-smooth muscle actin and B+ tenascin-C in chronic cardiac allograft rejection.

Chronic cardiac rejection is represented by cardiac allograft vasculopathy (CAV) and cardiac interstitial fibrosis (CIF) known to cause severe complications. These processes are accompanied by remarkable changes in the cardiac extra cellular matrix (cECM). The aim of our study was to analyse the cECM remodelling in chronic rejection and to elucidate a potential role of ED-A domain containing fibronectin (ED-A(+) Fn), alpha smooth muscle actin (ASMA) and B domain containing tenascin-C (B(+) Tn-C). A model of chronic rejection after heterotopic rat heart transplantation was used. Allografts, recipient and control hearts were subjected to histological assessment of rejection grade, to real-time PCR based analysis of 84 genes of ECM and adhesion molecules and to immunofluorescence labelling procedures, including ED-A(+) Fn, ASMA and B(+) Tn-C antibodies. Histological analysis revealed different grades of chronic rejection. By gene expression analysis, a relevant up-regulation of the majority of ECM genes in association with chronic rejection could be shown. For 8 genes, there was a relevant up-regulation in allografts as well as in the corresponding recipient hearts. Association of ASMA positive cells with the grade of chronic rejection could be proven. In CAV and also in CIF there were extensive co-depositions of ED-A(+) Fn, ASMA and B(+) Tn-C. In conclusion, chronic cardiac allograft rejection is associated with a cECM remodelling. ASMA protein deposition in CAV, and CIF is a valuable marker to detect chronic rejection. Interactions of VSMCs and Fibro-/Myofibroblasts with ED-A(+) Fn and B(+) Tn-C might functionally contribute to the development of chronic cardiac rejection.

Induced expression of lectin-like oxidized ldl receptor-1 in vascular smooth muscle cells following Chlamydia pneumoniae infection and its down-regulation by fluvastatin.

Microorganisms such as Chlamydia pneumoniae have been shown to infect vascular cells and are believed to contribute to vascular inflammation and atherosclerotic plaque development. Plasma levels of oxidized low density lipoprotein (oxLDL) have received considerable attention as potential predictors of prognosis in atherosclerotic diseases. Lectin-like oxidized LDL receptor-1 (LOX-1) is one of the major receptors for oxidized LDL. It was investigated whether C. pneumoniae infection can stimulate expression of LOX-1 in vascular smooth muscle cells. Expression of LOX-1 in VSMC was measured by RT-PCR and immunoblotting following C. pneumoniae infection. To examine the pharmacological effect of a HMG-CoA reductase inhibitor on LOX-1 expression, cells were co-incubated with fluvastatin immediately after infection. A dose and time dependent expression of LOX-1mRNA and protein was found in C. pneumoniae infected SMC. After heat and UV light treatment of the chlamydial inoculum the level of LOX-1 was reduced to that of mock-infected cultures. Furthermore, treatment of infected cells with fluvastatin decreased LOX-1 expression to baseline levels. The up-regulation of LOX-1 induced by C. pneumoniae could lead to continued lipid accumulation in atherosclerotic lesions. Together with the widespread expression of LOX-1, this might contribute to the epidemiologic link between C. pneumoniae infection and atherosclerosis. The effect of lowering the LOX-1 expression by fluvastatin may provide a pharmacological option of limiting oxLDL uptake via its scavenger receptor.

Segmented Poincaré plot analysis for risk stratification in patients with dilated cardiomyopathy.

BACKGROUND: The prognostic value of heart rate variability in patients with dilated cardiomyopathy (DCM) is limited and does not contribute to risk stratification although the dynamics of ventricular repolarization differs considerably between DCM patients and healthy subjects. Neither linear nor nonlinear methods of heart rate variability analysis could discriminate between patients at high and low risk for sudden cardiac death. OBJECTIVE: The aim of this study was to analyze the suitability of the new developed segmented Poincaré plot analysis (SPPA) to enhance risk stratification in DCM. METHODS: In contrast to the usual applied Poincaré plot analysis the SPPA retains nonlinear features from investigated beat-to-beat interval time series. Main features of SPPA are the rotation of cloud of points and their succeeded variability depended segmentation. RESULTS: Significant row and column probabilities were calculated from the segments and led to discrimination (up to p<0.005) between low and high risk in DCM patients. CONCLUSION: For the first time an index from Poincaré plot analysis of heart rate variability was able to contribute to risk stratification in patients suffering from DCM.