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Aims While the CLOSE protocol proposes a maximally tolerable interlesion distance (ILD) of 6 mm for ablation index ablation index-guided atrial fibrillation (AF) ablation, a target ILD has never been defined. This randomized study sought to establish a target ILD for ablation index-guided AF ablation. Methods and results Consecutive patients scheduled for first-time pulmonary vein (PV) isolation (PVI) were randomly assigned to ablation protocols with a target ILD of 5.0–6.0 mm or 3.0–4.0 mm, with the primary endpoint of first-pass PVI. In compliance with the CLOSE protocol, the maximum tolerated ILD was 6.0 mm in both study protocols. A target ablation index of ≥550 (anterior) or ≥400 (posterior) was defined for the ‘5–6 mm’ protocol and ≥500 (anterior) or ≥350 (posterior) for the ‘3–4 mm’ protocol. The study was terminated early for superiority of the ‘3–4 mm’ protocol. Forty-two consecutive patients were randomized and 84 ipsilateral PV pairs encircled according to the study protocol. First-pass PVI was accomplished in 35.0% of the ‘5–6 mm’ group and 90.9% of the ‘3–4 mm’ group (P Conclusion In ablation index-guided AF ablation, an ILD of 3.0–4.0 mm should be targeted rather than 5.0–6.0 mm. Moreover, the lower target ILD may allow for less extensive ablation at each given point.

Aims Traditional echocardiographic parameters for the assessment of suspected cardiac amyloidosis (CA) are of limited diagnostic accuracy. We sought to explore differences and the discriminative value of phasic left atrial strain (LAS) reductions and of regional longitudinal left ventricular (LV) strain alterations (relative apical sparing; RELAPS) in CA and other causes of LV wall thickening (LVH). Methods and results We included 54 patients with unclear LVH (mean septal diastolic wall thickness 17.8 ± 3.5 mm); CA was bioptically confirmed in 35 patients (8 mATTR, 6 wtATTR, 20 AL, and 1 AA amyloidosis) and LVH in 19 subjects. We analysed RELAPS as well as LA reservoir (LASr), conduit (LAScd), and contraction strain (LASct) using 2D speckle tracking echocardiography (EchoPAC software, GE). RELAPS was higher (1.37 ± 0.94 vs. 0.86 ± 0.29, P < 0.007), whereas atrial mechanics were significantly reduced in CA (LASr, LAScd, and LASct: 9.7 ± 5.2%, −6.5 ± 3.5%, and −5.0 ± 4.1% in CA; and 22.7 ± 7.8%, −13.9 ± 5.2%, and −13.0 ± 5.5% in LVH, respectively; P < 0.001 each). With an area under the curve (AUC) of 0.91 [95% confidence interval (CI) 0.82–0.99], LASr showed a higher diagnostic accuracy in discriminating CA than RELAPS (AUC 0.74, 95% CI 0.59–0.88). LASr and LAScd remained significantly associated with CA in a multivariate regression model. Conclusion Phasic LAS was significantly reduced in patients with CA and showed a higher diagnostic accuracy in discriminating CA than RELAPS. The additional assessment of phasic LAS may be useful to rule in the possible diagnosis of CA in patients with unclear LVH.

Background Echocardiographic hallmarks of cardiac amyloidosis (CA), such as increased wall thickness of the LV and sparkling appearance of the myocardium, are limited by a reduced diagnostic accuracy. Purpose We sought to evaluate the diagnostic value of phasic left atrial strain alterations and of regional global longitudinal systolic LV strain (LVGLS) reductions in patients with CA and with other forms of LV hypertrophy. Methods Standard apical 4-chamber views were stored for offline analysis (Vivid E9, GE, Vingmed, Horton) in 54 patients who underwent endomyocardial biopsy for unclear LV hypertrophy. We then analyzed LVGLS as well as LA reservoir, conduit, and contraction strain using 2D speckle tracking echocardiography (2DSTE; EchoPAC software, GE). To assess regional LVGLS, the average of apical strain values / (average of mid + basal LV strain values) was calculated (relative apical sparing; RELAPS). Receiver operating characteristic (ROC) curve analyses and a multivariate logistic regression analysis were performed to investigate the diagnostic value of the respective LA and LV deformation analysis. Results CA was bioptically confirmed in 34 patients (13 TTR, 1 AA, 20 AL amyloidosis). In 18 patients, myocardial biopsy revealed other forms of LV hypertrophy, such as hypertensive heart disease (n = 2), hypertrophic cardiomyopathy (n = 12), and inflammatory myocardial diseases (n = 4). Mean septal wall thickness (17.7 ± 2.9 mm and 17.9 ± 4.3 mm) and left atrial volume index (43.8 ± 12.2 and 44.1 ± 17.2) were not different between groups. RELAPS was significantly higher in patients with CA (1.37 ± 0.94 vs. 0.86 ± 0.29, p1.0; p Conclusions LA strain during all three phases of the atrial cycle was significantly reduced in patients with CA compared to other forms of LVH, and showed a markedly higher diagnostic accuracy than regional LV strain analysis, with LA reservoir strain showing highest discriminative value. The assessment of LA strain, as part of a comprehensive echocardiographic assessment, may be useful to rule-in the possible diagnosis of CA in patients with unclear LV hypertrophy.

Background Tenting of the mitral leaflets is a major pathophysiological factor contributing to functional mitral regurgitation (FMR). A novel software tool allows automated quantification of the tenting volume (TnV) by 3D transesophageal echocardiography (TEE). The aims of this study are to investigate the correlations of biometric patient characteristics with the TnV and whether a threshold value for the diagnosis of a moderate or severe FMR can be calculated for the TnV. Methods This explorative and hypothesis-generating study analyzed the TnV of the mitral valve obtained by clinically indicated TEE. The mid-systolic, threefold calculated and averaged TnV from 80 patients with no or mild FMR and 27 patients with moderate or severe FMR was determined using the TomTec 4D MV Assessment tool. Results The TnV correlated significantly with the body size (r = 0.341), the weight (r = 0.272), and the body surface area (r = 0.320). After the adjustment to the body size, a threshold value of 1.25 cm3 /m was determined for the TnV by using a receiver-operating characteristic curve. This value distinguished moderate to severe from none to mild FMR with a sensitivity of 85% and a specificity of 71%. The intra-observer variability and inter-observer variability were determined to be 0.96 and 0.85, respectively. Conclusions Automated assessment of TnV has the potential to support the diagnostic evaluation of FMR. Further studies are needed to validate this result, detect additional factors influencing the size of the TnV, and determine further thresholds for any degree of FMR.

Objective The newly introduced noninvasive myocardial work analysis could potentially be beneficial in predicting the best timing for aortic valve replacement as well as clinical outcomes in patients with high grade aortic valve stenosis (AS), which is the leading valvular disease in the modern aging society. However, to date there is little data on the applicability of the method in the setting of extremely increased left ventricular (LV) afterload. Purpose In this pilot study, we aimed to apply myocardial work analysis in patients with increased LV afterload due to severe AS and to investigate the differences of myocardial work parameters in patients with different AS entities. In addition, we analyzed the early changes of myocardial work after the afterload reduction by transcatheter aortic valve replacement (TAVR). Methods We retrospectively studied echocardiographic data of 28 consecutive patients with severe AS before and 7 days after TAVR. Global Work Index (GWI), Global Constructive Work (GCW), Global Wasted Work (GWW) and Global Work Efficiency (GWE) were calculated using commercially available software based on noninvasive pressure-strain loops. In order to correct for underestimation of intraventricular pressure, we added the mean aortic valve pressure gradient to the peripheral systolic blood pressure used by the software. Results From the included patients (mean age 76 ± 10 years) 13 were classified as having normal flow (NF) severe AS, 8 had low flow low gradient (LFLG) and 7 paradoxical low flow low gradient (PLFLG) AS. GWI and GCW were significantly lower in patients with LFLG AS compared to patients with NF or PLFLG AS (936 ± 528 mmHg% vs. 2493 ± 485 mmHg% vs. 1959 ± 469 mmHg% [p Conclusion In this pilot study we applied the adapted myocardial work analysis in patients with increased afterload due to severe AS. We have shown that GCW and GWI are significantly higher in patients with NF AS when compared to LFLG and PLFLG AS. The differences between the groups persisted early after TAVR in spite of significant reduction of GWI and GWC in patients with NF AS. The clinical and prognostic importance of these findings are still to be investigated in a bigger cohort study.

Background: This study aimed to assess the association of mid-regional (MR) pro-adrenomedullin (MR-proADM) and MR-pro-A-type natriuretic peptide (MR-proANP) in comparison to N-terminal pro-natriuretic peptide (NT-proBNP) with outcome in patients with aortic stenosis (AS) treated with transcatheter aortic valve implantation (TAVI). Methods: One hundred consecutive TAVI patients were included in this prospective study. Association of preinterventional levels of MR-proADM, MR-proANP, NT-proBNP, C-reactive protein (CrP), and high-sensitive cardiac Troponin T (hsTN) with 30-day and 1-year outcome was analyzed. Results: There was no association with 30-day outcome, but all markers were associated with 1-year cardiovascular events and all-cause mortality. The combined biomarker analysis further improved risk prediction. Conclusions: In TAVI patients MR-proADM, MR-proANP, and NT-proBNP are promising predictors of adverse events within 1 year. Integration of these biomarkers into decision pathways may help to identify patients at higher risk.

AIM We aim to determine normative reference data of phasic right atrial (RA) strain and to investigate determinants, possible clinical implications as well as feasibility and reproducibility of RA strain analysis. METHODS AND RESULTS Right atrial strain was analyzed in 266 participants of the cross-sectional Berlin Female Risk Evaluation (BEFRI) study using 2D speckle-tracking echocardiography (2D STE). To determine reference values, phasic RA strain was determined in a subgroup of 123 individuals without known cardiovascular diseases or risk factors. Mean RA reservoir strain (RAS), RA conduit, and contraction strain in this reference group were 44.9 ± 11.6%, 27.1 ± 9.5%, and 17.0 ± 5.9%, respectively. Regarding possible clinical implications, RAS was significantly reduced in women with a BMI ≥ 25, compared with women with a BMI

Background Although initial hemodynamics of percutaneously implanted aortic bioprostheses compare favorably to surgically implanted valves, the durability of the flow characteristics remains unknown. As biological prostheses are at potential risk for early degeneration, the aim of our study was to compare Doppler hemodynamics and effective orifice area (EOA) directly after and at least 1 year after valve implantation. Methods In this monocentric, prospective study, we determined peak velocity, peak and mean systolic gradients, and EOA by echocardiography in 75 patients (Edwards SAPIEN, n = 20; CoreValve, n = 55) 1 week (median 7 ± 25 days) and 1 year (median 378 ± 157 days, maximum 1034 days) after transcatheter aortic valve implantation (TAVI). Results After 12 months, Doppler performance of the aortic valve prostheses remained unchanged. The peak instantaneous velocity was 1.9 ± 0.4 m/s directly after TAVI versus 1.8 ± 0.5 m/s (P = ns) at follow-up, with a mean gradient of 8.5 ± 3.7 mmHg and 8.1 ± 4.2 (P = ns), respectively. Interestingly, the degree of mitral regurgitation (MR) decreased significantly (P = 0.007) over time, and the severity of aortic regurgitation (AR) remained unchanged during follow-up (P = ns). Conclusion For at least 1 year after TAVI, the excellent Doppler hemodynamics and EOA are preserved in transcatheter aortic valve prostheses, and the severity of MR decreased significantly. In addition, we found no evidence of early valve deterioration or progression of AR.

Introduction Atrioventricular (AV) block is a frequent complication of transcatheter aortic valve implantation (TAVI). TAVI is routinely performed under anticoagulation using heparin, which potentially may lead to an increased bleeding rate in patients who undergo permanent pacemaker (PPM) implantation immediately after TAVI. As the number of TAVI procedures continues to rise, data on the optimal management of TAVI-related AV block are needed. Therefore, the aim of our study was to analyze PPM implantation-related complications after TAVI. Methods We retrospectively collected data on PPM implantations after TAVI in our center from January 2010 to December 2012. In total, we included 30 patients who received a PPM for TAVI-related AV block. Twelve patients (group A) underwent PPM implantation on the day of TAVI. In 18 patients (group B), PPM implantation was performed at least 1 day after TAVI (3.8 ± 4.5 days). Since all patients undergoing TAVI receive dual antiplatelet therapy (DA-therapy), we compared all implantations after TAVI with a historic patient cohort that underwent PPM implantation under DA-therapy. Results Procedure times, fluid loss via drainage systems, and drainage times were neither significantly different between groups A and B nor between all PPM implantations after TAVI compared to the historic control group. Conclusion PPM implantation immediately after TAVI is safe and can be performed without increased rate of complications.

The aim of this study was to evaluate the efficacy of the chemokine CCL19 (ELC) as an adjuvant for intradermal gene gun delivery of Her2/neu DNA and to investigate the role of B cells in CCL19-mediated enhancement of immune responses. Balb/c mice were immunized intramuscularly (i.m.) on days 1 and 15 with plasmid DNA (pDNA) (100 μg DNA) or intradermally (i.d.) by gene gun delivery (1-2 μg DNA). Administration of pDNA encoding Her2/neu (pDNA(Her2/neu) was compared with pDNA(Her2/neu) plus pDNA(CCL19), pDNA(CCL19), mock vector or uncoated gold particles/phosphate-buffered saline (PBS). Tumor challenge was performed subcutaneously on day 25 with syngeneic Her2/neu(+) tumor cells (D2F2/E2). Intradermal immunization by gene gun led to an enhancement of tumor protection by the DNA vaccine as compared with i.m. immunization. The protective effect of the vaccine was further enhanced by coadministration of pDNA(CCL19) both after i.m. and i.d. immunization. Tumor protection was associated with Her2/neu-specific T cell and humoral immune responses. Experiments in B-cell-deficient μMT mice showed that B cells are crucial for CCL19-mediated enhancement of tumor rejection, most likely as antigen-presenting B cells. DNA vaccines against Her2/neu may play a future role in the treatment of Her2/neu-positive breast cancer patients in a clinical situation of minimal residual disease.

Transarterial aortic valve implantation (TAVI) is a promising method for the treatment of high-risk patients with aortic stenosis. Because gender differences are known in aortic stenosis, the aim of this study was to compare procedural and short-term outcomes, left ventricular remodeling, and inflammatory status after TAVI in men and women. One hundred consecutive patients (42 men, 58 women) who underwent transfemoral TAVI (CoreValve in 83%, SAPIEN in 17%) were prospectively analyzed. Aortic stenosis severity was higher in women (mean valve area 0.7 ± 0.3 vs 0.8 ± 0.2 cm(2)). Women had better ejection fractions, smaller end-diastolic and end-systolic diameters, and more concentric hypertrophy at baseline. There were no differences in device success rate (99%), 30-day total mortality (2.4% in men, 3.4% in women), stroke (2.4% in men, 1.7% in women), or pacemaker rate (26.2% in men, 15.5% in women). Periprocedural complications and 3-month outcome were not different between the genders. After TAVI, regression of hypertrophy occurred in men and women, but improvement of the ejection fraction was significant only in women. N-terminal pro-B-type natriuretic peptide decreased to similar levels in the 2 genders. C-reactive protein and interleukin-6, elevated at baseline more in men than in women, decreased after TAVI and normalized at 3 months only in women. In conclusion, women clinically benefit from TAVI to a degree similar to that of men. However, there are gender differences involving the recovery response of the left ventricle after TAVI.

Aims Transcatheter aortic valve implantation (TAVI) is a new therapy for severe aortic stenosis in high-risk patients. So far, no reference values for the echocardiographic assessment of this new class of heart valves have been established. The aim of our study was to determine Doppler haemodynamics and the effective orifice area (EOA). Methods and results We retrospectively analysed the earliest transthoracic echocardiographic examinations of 146 stable patients after successful TAVI (median 8 ± 20 days). Doppler examinations were analysed for peak instantaneous velocity, peak, and the mean systolic gradient. EOA was determined using the continuity equation. Patients with severe paravalvular aortic or mitral valve regurgitation were excluded. The overall peak instantaneous velocity ( n = 146) was 2.0 ± 0.4 m/s with a peak systolic gradient of 17.1 ± 7.4 mmHg and a mean gradient of 9.3 ± 4.5 mmHg. The mean EOA was 1.82 ± 0.43 cm2 with an indexed EOA of 1.0 ± 0.27 cm2/m2. In general, all prostheses showed similar values—with the exception of the Edwards Sapien 23 mm which was associated with higher velocities and peak pressure gradients. Conclusion Our study establishes the normal range for Doppler haemodynamics of four transcatheter aortic valve prostheses. Compared with previously published data of surgically implanted bioprostheses percutaneous valves tend to have similar EOA values but lower mean peak velocities and pressure gradients. In comparison with physiological haemodynamics; however, this new class of heart valves is still associated with a mild obstruction.

Background DNA vaccination is an attractive approach for tumor vaccination because plasmid DNA (pDNA) can be used as a ‘general vaccine’ across major histocompatibility complex barriers. Coexpression of immunomodulatory molecules can help to amplify the immunogenicity of DNA vaccines. CCL19 (ELC) is a CC chemokine with immunoregulatory properties, binding to the chemokine receptor CCR7 that is expressed on dendritic cells (DCs) and T cells. In vivo, CCL19 is a key regulator for the interactions between DCs and T cells in regional lymph nodes. Methods pDNA encoding Her2/neu and CCL19 was used as an intramuscular vaccine. Vaccination was performed in BALB/c mice, which were subsequently challenged with syngeneic Her2/neu+ tumor cells. Groups of mice were immunized with pDNA(Her2/neu) plus pDNA(CCL19), pDNA(Her2/neu) plus pDNA(CCL19) plus pDNA(GM-CSF), pDNA(Her2/neu) plus pDNA(GM-CSF), pDNA(Her2/neu), pDNA(CCL19), pDNA(GM-CSF) or mock vector. Tumor protection by the vaccine and immune responses were monitored. Results Coadministration of pDNA(Her2/neu) and pDNA(CCL19) led to substantial improvement of tumor protection by the vaccine and induced a TH1-polarized, Her2/neu-specific immune response. Forty-seven days after the tumor challenge, 58% of the mice coinjected with pDNA(Her2/neu) and pDNA(CCL19) remained tumor-free compared to 22% after vaccination with pDNA(Her2/neu) alone. Additional administration of pDNA(GM-CSF) led to further improvement of tumor protection and an amplification of Her2/neu-specific immune responses. Conclusions CCL19 is able to induce a TH-1 polarization of the anti-Her2/neu immune response, which can be further amplified by granulocyte macrophage-colony-stimulating factor (GM-CSF). Clinical use of a pDNA(Her2/neu-CCL19 ± GM-CSF) vaccine might be promising in Her2/neu + breast cancer in the clinical situation of minimal residual disease. Copyright © 2012 John Wiley & Sons, Ltd.

Secondary lymphoid-tissue chemokine (SLC/CCL21) is a CC chemokine that is constitutively expressed in various lymphoid tissues and binds to chemokine receptor CCR7 on mature dendritic cells (DCs) and distinct T-and B-cell sub-populations. In vivo, CCL21 regulates the encounters between DC and T cells and thus is a key regulator of adaptive immune responses. We asked whether CCL21 is able to augment immunogenicity of a DNA-based vaccine against Her2/neu in a Balb/c mouse model with syngeneic Her2/neu+ tumor cells (D2F2/E2). Mice were vaccinated intramuscularly with plasmid DNA (pDNA) on day 1 and boosted on day 15; tumor challenge was performed subcutaneously on day 25. Coexpression of CCL21 and Her-2/neu resulted in induction of a TH1-polarized immune response and substantial improvement of the protective effect of the DNA vaccine. Coexpression of tumor antigen pDNA(Her2/neu) with both pDNA(GM-CSF) and pDNA(CCL21) as adjuvants led to further improvement of protection by the vaccine (70% tumor-free mice on day 35 vs 40% with either adjuvant alone vs 5-10% with tumor antigen alone). Our results show that CCL21 is a potent adjuvant for DNA vaccination, particularly in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF). Clinical use of a pDNA(Her2/neu/CCL21/GM-CSF) vaccine might be particularly promising in minimal residual Her2/neu+ breast cancer.

Coexpression of tumor antigens together with immunomodulatory molecules is a strategy in DNA vaccination aiming at an amplification of the antitumor immune response. Epstein-Barr virus-induced-molecule-1-ligand-chemokine (ELC/CCL19) is a CC chemokine that binds to the chemokine receptor CCR7. CCR7 is expressed on mature dendritic cells (DC) and distinct T- and B-cell subpopulations. CCL19 (ELC) is mainly expressed in secondary lymphoid organs and plays a central role in regulating the encounters between DC and T cells. We asked whether CCL19 is able to augment immunogenicity of a DNA vaccine in a C57BL/6 mouse model with syngeneic MCA205 (beta-gal) tumor cells. Mice were vaccinated twice intramuscularly on days 1 and 15 and tumor challenge was performed subcutaneously on day 25. Coadministration of plasmid DNA (pDNA) (beta-gal) plus pDNA (CCL19) was compared with pDNA (beta-gal), pDNA (CCL19), mock vector and phosphate-buffered saline (PBS) alone. Coexpression of CCL19 resulted in enhancement of a Th1-polarized immune response with substantial improvement of the protective effect of the DNA vaccine. Immunohistochemical staining revealed an increased CD8+ T-cell infiltration in the tumor tissue of mice that had been immunized with pDNA (beta-gal) plus pDNA (CCL19). We conclude that CCL19 is an attractive adjuvant for DNA vaccination able to augment antitumor immunity and that this effect is partially caused by enhanced CD8+ T-cell recruitment.

Introduction: Until now, a reliable biomarker to predict the short- or long-term outcome for patients undergoing TAVI is still missing. Galectin-3, a novel marker indicative for myocardial fibrosis, has prognostic value in heart failure. Our goal was to investigate whether galectin-3 is suited for risk assessment in TAVI patients. Methods: We included 101 patients undergoing TAVI in this prospective, single-center, observational study. Baseline galectin-3 levels were correlated to the VARC 30-day safety and one-year efficacy endpoint as well as to total mortality and cardiovascular events at one year. Results: The VARC 30-day safety endpoint was reached by 24 patients. At one year, 43 patients met the VARC efficacy endpoint, 16 patients died, and 23 cardiovascular events were recorded. At baseline, mean galectin-3 level for the entire group was 18.1 (± 11.1) ng/ml. Of the 101 patients, 36 had a galectin-3 value above the cut-off value of 17.8 ng/ml. These patients had significantly higher systolic pulmonary artery and capillary wedge pressures. The hazard ratio in patients with galectin-3 > 17.8 ng/ml was 3.36 (95 % confidence interval, CI: 1.47 - 7.69; p = 0.004) for the VARC 30-day safety endpoint, 5.12 (95 % CI: 2.10 - 12.47; p < 0.001) for one-year cardiovascular events, and 4.48 (95 % CI: 1.56 - 12.91; p = 0.005) for all-cause mortality. This prediction remained stable even after adjusting for possible confounders including age, sex, glomerular filtration rate, and NT-proBNP. Furthermore, the prediction was even more valuable when combining galectin-3 with NT-proBNP for cardiovascular events (HR = 6.39; CI: 2.87-23.89; p < 0.001) and all-cause mortality (HR = 8.28; CI: 2.01-23.59; p < 0.001). Conclusions: Elevated galectin-3 levels are independently associated with adverse outcome after TAVI. Combining galectin-3 with NT-proBNP provides additive predictive value of risk stratification.

Sex differences exist in pathogenesis, clinical presentation, and outcome in aortic stenosis (AS). However, only limited information is available concerning sex differences in transcatheter aortic valve implantation (TAVI). The aim of the present study is a comprehensive meta-analysis of studies that investigate differences between men and women in outcome after TAVI.We screened PUBMED, MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. Inclusion criteria were: AS treated with all forms of TAVI, studies specifically targeting sex/gender differences, and at least 2 of the following outcome data: 30-day all-cause death, mortality during follow-up, major vascular complications, major bleeding, pacemaker, or stroke rate (30 days). Studies were excluded if they considered female gender merely in subgroup analysis.We included 14 observational studies with a total of 7,973 patients (4,242 women, 3,731 men). At 30 days (12 studies, 3,044 women, 2,784 men), female sex was associated with a significantly lower mortality rate (odds ratio [95% confidence interval] 0.78 [0.64, 0.96]). Of the 14 studies included for analysis, 12 provided data on mortality during follow-up that likewise show a survival advantage for women (OR 0.70 [0.59, 0.82]). Whereas the major vascular complication rate was greater in women (11 studies, 3,731 women, 3,342 men; OR 1.72 [1.41, 2.09]), major bleeding (8 studies, 2,124 women, 2,100 men; OR 1.13 [0.95, 1.33]) was not. Pacemaker and stroke rate were not significantly different between the groups.In treatment with TAVI, there is evidence for a significantly greater overall survival benefit in women over men.

Background Transcatheter aortic valve implantation (TAVI) has been shown to improve prognosis of high-risk patients. Data, however, concerning the impact of TAVI on regional and global left atrial (LA) and left ventricular (LV) mechanics in varying entities of severe aortic stenosis (AS) are sparse, particularly in patients with paradoxical low-flow (PLF) AS or with reduced LV ejection fraction (LVEF). This study evaluated the effects of TAVI on LA and LV mechanics in varying entities of AS 12 months after implantation. Methods and results A total of 54 consecutive patients with severe AS (24 with a normal LVEF and normal flow, 16 with PLF, and 14 with a reduced LVEF) were included. Speckle tracking echocardiography was performed before and 12 months after TAVI to determine LV global and regional longitudinal deformation as well as LA function (reservoir function, conduit phase, and active contraction). In all the three entities of AS, there was a significant improvement in global and regional LV longitudinal function (average global longitudinal strain: −14.1 ± 3.9% at baseline vs. −16.5 ± 4.0% after TAVI, P < 0.001). Interestingly, the beneficial effects were most pronounced in patients with PLF (−14.0 ± 2.9 vs. −17.0 ± 4.4%, P < 0.031). Moreover, the atrial reservoir and conduit function recovered significantly after TAVI in all patients. Conclusion In conclusion, regardless of the underlying AS entity, TAVI improves global and regional LV and LA mechanics within 12 months.

Atrioventricular (AV) block is a frequent complication of transcatheter aortic valve implantation (TAVI). TAVI is routinely performed under anticoagulation using heparin, which potentially may lead to an increased bleeding rate in patients who undergo permanent pacemaker (PPM) implantation immediately after TAVI. As the number of TAVI procedures continues to rise, data on the optimal management of TAVI-related AV block are needed. Therefore, the aim of our study was to analyze PPM implantation-related complications after TAVI.We retrospectively collected data on PPM implantations after TAVI in our center from January 2010 to December 2012. In total, we included 30 patients who received a PPM for TAVI-related AV block. Twelve patients (group A) underwent PPM implantation on the day of TAVI. In 18 patients (group B), PPM implantation was performed at least 1 day after TAVI (3.8 ± 4.5 days). Since all patients undergoing TAVI receive dual antiplatelet therapy (DA-therapy), we compared all implantations after TAVI with a historic patient cohort that underwent PPM implantation under DA-therapy.Procedure times, fluid loss via drainage systems, and drainage times were neither significantly different between groups A and B nor between all PPM implantations after TAVI compared to the historic control group.PPM implantation immediately after TAVI is safe and can be performed without increased rate of complications.

Aortic stenosis (AS) leads to remodeling of the left heart. Strain measurements enable the assessment of left atrial (LA) mechanics. The goal of this study was to evaluate the short-term effects of transcatheter aortic valve implantation (TAVI) on LA myocardial deformation as well as left ventricular (LV) diastolic function.Thirty-two patients with severe AS were prospectively enrolled and examined before and 8.2 ± 3.3 days after TAVI. Speckle-tracking echocardiography of the basal septal and lateral segments of the left atrium was performed to determine peak positive strain (R(LA)), strain during early diastole (E(LA)), and, if feasible, strain during atrial contraction (A(LA)). Assessment of LV diastolic function included standard indices, the atrial fraction, and LA volumes.Compared with baseline, the mean atrial reservoir (R(LA)) (24.0 ± 11.2% vs 32.2 ± 14.0%, P.001) and conduit function (R(LA) - E(LA)) (13.9 ± 5.5% vs 20.8 ± 8.1%, P.001) improved significantly after TAVI. There was a significant reduction in deceleration time (242 ± 56 vs 195 ± 65 msec, P.001) and an improvement of pulsed-wave tissue Doppler-derived E' (5.5 ± 1.8 vs 7.3 ± 2.3 cm/sec, P = .01). Regarding LA volumes, only the minimal LA volume index changed significantly. In contrast, there was no improvement in atrial contraction, that is, contractile function (E(LA) - A(LA)) and atrial fraction. Moreover, the E/E' ratio remained unchanged.8.2 ± 3.3 days after TAVI, only the reservoir and conduit function of the left atrium improved, whereas LA contraction and LA volumes, except for the systolic volume index, remained unchanged. This was accompanied by improvement of early LV diastolic function, indicating acute recovery of LV relaxation and LA function.

Background Transcatheter aortic valve implantation (TAVI) is a promising therapy for patients with severe aortic stenosis (AS) and high perioperative risk. New echocardiographic methods, including 2D Strain analysis, allow the more accurate measurement of left ventricular (LV) systolic function. The goal of this study was to describe the course of LV reverse remodelling immediately after TAVI in a broad spectrum of patients with symptomatic severe aortic valve stenosis. Methods Thirty consecutive patients with symptomatic aortic valve stenosis and preserved LVEF underwent transfemoral aortic valve implantation. We performed echocardiography at baseline and one week after TAVI. Echocardiography included standard 2D and Doppler analysis of global systolic and diastolic function as well as 2D Strain measurements of longitudinal, radial and circumferential LV motion and Tissue Doppler echocardiography. Results The baseline biplane LVEF was 57 ± 8.2%, the mean pressure gradient was 46.8 ± 17.2 mmHg and the mean valve area was 0.73 ± 0.27 cm2. The average global longitudinal 2D strain of the left ventricle improved significantly from -15.1 (± 3.0) to -17.5 (± 2.4) % (p < .001). This was reflected mainly in improvement in the basal and medial segments while strain in the apex did not change significantly [-11.6 (± 5.2) % to -15.1 (± 5.5) % (p < .001), -13.9 (± 5.1) % to -16.8 (± 5.6) % (p < .001) and -19.2 (± 7.0) % to -20.0 (± 7.2) % (p = .481) respectively]. While circumferential strain [-18.1 (± 5.1) % vs. -18.9 (± 4.2) %, p = .607], radial strain [36.5 (± 13.7) % vs. 39.7 (± 17.2) %, p = .458] and the LVEF remained unchanged after one week [57.0 (± 8.2) % vs. 59.1 (± 8.1) %, p = .116]. Conclusion There is an acute improvement of myocardial longitudinal systolic function of the basal and medial segments measured by 2D Strain analysis immediately after TAVI. The radial, circumferential strain and LVEF does not change significantly in all patients acutely after TAVI. These data suggest that sensitive new echo methods can reliably detect early regional changes of myocardial function after TAVI before benefits in LVEF are detectable.

DNA vaccination is an attractive approach for tumor vaccination because plasmid DNA (pDNA) can be used as a 'general vaccine' across major histocompatibility complex barriers. Coexpression of immunomodulatory molecules can help to amplify the immunogenicity of DNA vaccines. CCL19 (ELC) is a CC chemokine with immunoregulatory properties, binding to the chemokine receptor CCR7 that is expressed on dendritic cells (DCs) and T cells. In vivo, CCL19 is a key regulator for the interactions between DCs and T cells in regional lymph nodes.pDNA encoding Her2/neu and CCL19 was used as an intramuscular vaccine. Vaccination was performed in BALB/c mice, which were subsequently challenged with syngeneic Her2/neu(+) tumor cells. Groups of mice were immunized with pDNA(Her2/neu) plus pDNA(CCL19), pDNA(Her2/neu) plus pDNA(CCL19) plus pDNA(GM-CSF), pDNA(Her2/neu) plus pDNA(GM-CSF), pDNA(Her2/neu), pDNA(CCL19), pDNA(GM-CSF) or mock vector. Tumor protection by the vaccine and immune responses were monitored.Coadministration of pDNA(Her2/neu) and pDNA(CCL19) led to substantial improvement of tumor protection by the vaccine and induced a TH1-polarized, Her2/neu-specific immune response. Forty-seven days after the tumor challenge, 58% of the mice coinjected with pDNA(Her2/neu) and pDNA(CCL19) remained tumor-free compared to 22% after vaccination with pDNA(Her2/neu) alone. Additional administration of pDNA(GM-CSF) led to further improvement of tumor protection and an amplification of Her2/neu-specific immune responses.CCL19 is able to induce a TH-1 polarization of the anti-Her2/neu immune response, which can be further amplified by granulocyte macrophage-colony-stimulating factor (GM-CSF). Clinical use of a pDNA(Her2/neu-CCL19 ± GM-CSF) vaccine might be promising in Her2/neu + breast cancer in the clinical situation of minimal residual disease.

Background: TAVI improves prognosis of high-risk patients. However, data concerning the impact of TAVI on regional and global LV mechanics in varying entities of severe AS are sparse, particularly in patients with paradoxical low flow aortic stenosis (PLF) or with reduced Left Ventricular Ejection Fraction (LVEF). This study evaluated the effects of Transcatheter Aortic Valve Implantation (TAVI) on Left Ventricular (LV) mechanics in varying entities of aortic stenosis (AS) 12 months after implantation. Methods: A total of 54 consecutive patients with severe AS (24 with normal LVEF and normal flow, 16 with PLF, and 14 with reduced LVEF) were included. Normal LVEF and normal flow were defined as LVEF ≥ 50% and SVI ≥ 35 ml/m2. Paradoxical low flow was defined as LVEF ≥ 50% and SVI < 35 ml/m2 and patients with reduced LVEF, as LVEF < 50%. Speckle tracking echocardiography was performed before and 12 months after TAVI to determine LV global and regional longitudinal deformation. Results: In three entities of AS, there was significant improvement of global and regional LV longitudinal function (global longitudinal strain: -14.1±3.9% at baseline vs. -16.5±4.0% after TAVI, P < 0.001). Interestingly, the beneficial effects were most pronounced in patients with PLF (-14.0±2.9% vs. -17.0±4.4%, P < 0.031) but was significant in all subgroups: normal EF (-16.1±3.4% vs. -18.1±3.3%, P = 0.012) and reduced EF (-10.5±3.1% vs. -13.5±3.2%, P = 0.026). ![Figure][1] Bull's-eye diagram Conclusion: Regardless of the underlying AS entity, TAVI improves global and regional left ventricular mechanics within 12 months. This improvement is more pronounced in patients with PLF. [1]: pending:yes

Objective: Despite the beneficial effects of regular endurance exercise on cardiovascular mortality and morbidity, complex ventricular arrhythmias and atrial fibrillation seem to be common in elite and amateur endurance athletes. Nevertheless, data on arrhythmias during endurance exercise is sparse. Our goal was to proof the feasibility for recording electrocardiogram (ECG) during marathon running, and to compare the first hour with the last hour of running. Methods: 11 healthy, male recreational athletes were equipped with a long-term Tele-ECG with continuous recording of the heart rhythm during running a marathon. All ECG data were directly transferred via mobile network from the device to the Telemedicine center (Campus, Berlin, Germany) for a subsequent online diagnosis ("Streaming-Telemedtechnology") The recorded data was analyzed offline. Results: One runner had to be excluded due to artifact superimposed recording quality. Therefore 10 male runners were included in our study and completed a full or a half marathon. No episodes of atrial fibrillation could be detected. Two participants showed less than 10 ventricular premature beats (VPB) during running (Lown classification I). In another two athletes 15 polymorphic VPB (Lown classification IIIa) and 117 VPB (Lown classification IV b), including 8 couplets and one triplet were observed, respectively. There was no significant difference between the first and last hour of running concerning the number of ventricular premature beats (3.4±10.8 vs. 1.6±4.4, P = ns), mean heart rate (139.8±32.6 vs. 130.6±39.2 bpm, P = ns), maximal heart rate (150.0±32.3 vs. 149.4±37.1 bpm, P = ns), rate corrected QT-interval (444.3±35.7 vs. 439.2±25.2 ms, P = ns). Concerning heart rate variability (HRV), it remained unchanged during marathon running {HRV triangular index 11.2±9.9 vs. 10.9±8.5, P = ns; Standard deviation of all NN intervals (SDNN) 85.4±67.0 vs. 109.0±62.7 ms, P = ns}. Conclusion: We showed that ECG recording and immediate transmission of the signal by telemedicine during marathon running is feasible. In general, ventricular and supraventricular arrhythmias were rare during endurance sport in our athletes. In addition, there were no significant changes in ECG parameters during marathon running.