Serum microRNA-1233 is a specific biomarker for diagnosing acute pulmonary embolism.

BACKGROUND: Circulating microRNAs (miRNAs) emerge as novel biomarkers in cardiovascular diseases. Diagnosing acute pulmonary embolism (PE) remains challenging due to a diverse clinical presentation and the lack of specific biomarkers. Here we evaluate serum miRNAs as potential biomarkers in acute PE. METHODS: We enrolled 30 patients with acute, CT (computed tomography)-angiographically confirmed central PE and collected serum samples on the day of emergency room admission (1st day) and from 22 of these patients 9 months thereafter. For comparison, we examined serum samples from patients with acute non ST-segment elevation myocardial infarction (NSTEMI, n = 30) and healthy individuals (n = 12). RESULTS: We randomly selected 16 out of 30 PE patients and screened sera from the acute (1st day) and chronic stages (9 months) for 754 miRNAs using microarrays and found 37 miRNAs to be differentially regulated. Across all miRNAs, miRNA-1233 displayed the highest fold change (FC) from acute to chronic stage (log2FC 11.5, p < 0.004). We validated miRNA-1233 by real-time quantitative polymerase chain reaction (RT-qPCR). In acute PE (1st day) we found elevated levels of miRNA-1233 in comparison to NSTEMI (log2FC 5.7, p < 0.0001) and healthy controls (log2FC 7.7, p < 0.0001). miRNA-1233 differentiated acute PE from NSTEMI patients and healthy individuals with 90 and 90 % sensitivity, and 100 and 92 % specificity [area under the curve (AUC) 0.95, p < 0.001 and 0.91, p < 0.001], respectively. CONCLUSIONS: This is the first report that identifies a miRNA that allows distinguishing acute PE from acute NSTEMI and healthy individuals with high specificity and sensitivity.

Kidney injury and mortality after transcatheter aortic valve implantation in a routine clinical cohort.

OBJECTIVES: We aimed at identifying predictors of renal impairment and its impact on long-term outcome after transcatheter aortic valve implantation (TAVI). BACKGROUND: Renal impairment is common in mostly elderly, multimorbid patients undergoing TAVI. The risk of periprocedural renal function impairment and its association with outcome is incompletely understood. METHODS: In 458 consecutive patients (mean age, 80.6 ± 7.0 years, 52.2% women) who underwent routine TAVI procedures, we assessed estimated glomerular filtration rate (eGFR) at baseline, during 72-hr postprocedure and at discharge. Over a median follow-up of 0.96 years, we observed 142 deaths. RESULTS: In multivariable-adjusted models, predictors of renal function deterioration within 72 hr were baseline eGFR (ß = 0.83, 95% confidence interval [CI] = 0.76/0.91; P < 0.0001), body mass index (ß = -1.20, 95% CI = 1.77/-0.62; P < 0.0001), and major access site complications (ß = -14.82, 95% CI = -26.52/-3.11; P = 0.013) including bleeding (ß = -11.97, 95% CI = -21.05/-2.89; P = 0.0099). Strongest renal function predictor of 1-year mortality in risk factor adjusted analyses was the change of eGFR within 72 hr (odds ratio, 0.97; 95% CI = 0.96/0.98; P < 0.0001). The addition of information on the change of eGFR increased the C-statistic of the logistic EuroSCORE (P = 0.021). CONCLUSIONS: In our routine TAVI sample, baseline eGFR, body mass index, and major access site complications mainly owing to bleeding were correlates of acute kidney injury after TAVI. Acute renal impairment was a risk factor for mortality and adverse cardiovascular events which provided risk information beyond the EuroSCORE.

Evolution of mitral valve procedural volumes in the advent of endovascular treatment options: Experience at an early-adopting center in Germany.

OBJECTIVES: Our objectives were to assess the evolution of surgical and endovascular mitral valve procedural volumes and to study utilization and reimbursement effects of transcatheter mitral valve repair (TMVR) at our center and to put these in perspective with the corresponding data at the national level. BACKGROUND: TMVR using the MitraClip system has been available in Germany since 2008 as a complementary treatment option for high-risk or inoperable patients. METHODS: Relevant procedure codes were identified for 2006-2012 and yearly utilization volumes obtained from our center's databases and from the national statistics office. Volumes were analyzed in total, and stratified by treatment approach. Procedure reimbursement at our center was determined for years 2007-2012. RESULTS: At our center, 378 MitraClip procedures were performed from 2008 to 2012. During this period, surgical volumes grew at an average of 10.6% annually (2008: 262; 2012: 392; 49.6% total growth rate). Total surgical and TMVR reimbursement increased from EUR 3.8 million (2007) to EUR 7.9 million (2012). By comparison, mitral valve procedural volumes grew by 56.1% from 2006 to 2012 at the national level, with TMVR constituting 9.1% of 20,328 procedures in 2012. Since the introduction of MitraClip, nationwide surgical procedural volumes grew at an average of 6.3% annually (2008: 14,477; 2012: 18,478; 27.6% total growth rate). CONCLUSIONS: Growth in procedural volumes during 2006-2012 reflects an increasing supply and subsequent demand for mitral valve procedures. The introduction of TMVR has contributed to overall growth, and has not reduced continued growth in surgical volumes. Our center-specific analysis suggests a "halo effect" of an integrated approach to mitral valve disease contributing to additional growth in surgical and overall reimbursement volumes.

Blood transfusion is associated with impaired outcome after transcatheter aortic valve implantation.

OBJECTIVES: We sought to evaluate the relationship of blood transfusion after transcatheter aortic valve implantation (TAVI) and mid-term outcome to improve patient selection and periprocedural treatment. BACKGROUND: Increasing evidence suggests a negative influence of blood transfusion on outcomes of patients with cardiovascular diseases. While the adverse impact of bleeding events on survival has been documented after TAVI, data on the impact of postoperative blood transfusions are scarce. METHODS: TAVI was performed in 700 consecutive patients; 14.7% of TAVI patients suffered from bleeding or access site complications and were excluded from analysis to minimize confounding. Outcomes were analyzed with emphasis on blood transfusions and according to the Valve Academic Research Consortium definitions. Median follow-up duration was 364 days. Multivariable analyses were performed to identify predictors for transfusion and 1-year mortality. RESULTS: 33.0% of patients received blood transfusions after TAVI, irrespective of access choice. Blood transfusions were associated with a higher baseline risk profile (median logistic EuroSCORE 21.0 vs. 17.0%), increased rates of postoperative complications and impaired survival (21.2 vs. 36.1% all-cause 1-year mortality). Transfusion was an independent predictor of mortality at 1 year (OR 2.78 [CI 1.59-4.86]). Low body mass index (OR 0.94 [0.89-1.0]), low baseline hemoglobin (OR 0.39 [0.33-0.47]) and combined anticoagulation/antiplatelet therapy were identified as independent predictors of blood transfusion after TAVI. CONCLUSIONS: Blood transfusions were frequently required after TAVI even in the absence of overt bleeding or access site complications and were identified as an independent predictor of impaired mid-term outcome. Optimization of baseline factors, strict blood conservation strategies, and individualized antiplatelet or anticoagulant regimens may improve outcome after TAVI.

Carcinoid Heart Valve Disease: Transcatheter Pulmonary Valve-In-Valve Implantation in Failing Biological Xenografts.

BACKGROUND AND AIM OF THE STUDY: Carcinoid heart valve disease (CHVD) occurs as the cardiac manifestation of carcinoid syndrome (also known as Hedinger's syndrome), which develops secondary to neuroendocrine tumor activity. CHVD almost exclusively affects right-sided heart valves, since circulating serotonin is metabolized by pulmonary endothelial cells, thus sparing left-sided valves. Replacement of the tricuspid and pulmonary valve is a well-established and feasible therapeutic option for these patients. Whether biological valve substitutes are subject to a continuous degenerative process is not entirely clear at present due to the rarity of the disease and inconclusive findings in the current literature. METHODS: Herein are presented the details of two patients suffering from advanced CHVD who had undergone previous combined tricuspid valve replacement (TVR) and pulmonary valve replacement (PVR) using biological xenografts, and had subsequently been readmitted with failure of the pulmonary valve substitute. RESULTS: Due to the increased risk for repeat surgical valve replacement, the patients were treated by percutaneous stent implantation into the pulmonary artery, followed by the implantation of a balloon- expandable transcatheter heart valve (THV). The procedures were feasible and safe through the intact TVR. CONCLUSION: This strategy resulted in a favorable acute outcome in both patients, with adequate valve function and no PVL as documented by TTE, although the transvalvular gradients were elevated in both cases. The patients had an uneventful postoperative course and were discharged home in timely fashion. Whether the residual elevated transvalvular gradients following the valve-in-valve procedures, or an early degeneration of the implanted bioprostheses, will have a negative impact on the patients' further course will become clear in the future.

Predicting Risk in Transcatheter Aortic Valve Implantation: Comparative Analysis of EuroSCORE II and Established Risk Stratification Tools.

BACKGROUND: The logistic European System for Cardiac Operative Risk Evaluation (logEuroSCORE) II was developed to improve prediction of mortality in cardiac surgery. However, no specific tools are available for risk prediction in transcatheter aortic valve implantation (TAVI). The recently introduced EuroSCORE II was compared with established risk scores. PATIENTS AND METHODS: We assessed 457 consecutive patients (80.5 ± 7.1 years, 52.3% female) undergoing TAVI. Preoperative risk evaluation included logEuroSCORE I, EuroSCORE II, Society of Thoracic Surgeons (STS), Ambler, and Parsonnet scores. Validity was assessed by receiver-operating characteristic (ROC) and area under the curve (AUC). RESULTS: A 30-day mortality was 9.6% (44/457). Calculated scores were logEuroSCORE I 22.0%, confidence interval (CI) 21.0 to 24.6; EuroSCORE II 7.0%, CI 6.4 to 8.1; STS 7.9%, CI 7.7 to 9.5; Ambler score 6.9%, CI 5.7 to 7.0; and Parsonnet score 23.8%, CI 20.9 to 24.1. ROC analyses demonstrated no predictive value: logEuroSCORE I AUC 0.56, CI 0.47 to 0.65; EuroSCORE II AUC 0.54, CI 0.46 to 0.63; STS AUC 0.57, CI 0.49 to 0.66; Ambler AUC 0.52, CI 0.43 to 0.60; and Parsonnet AUC 0.51, CI 0.43 to 0.60. Accuracy and thresholds were measured on behalf of Youden index. Accuracy ranged between 44.2% (Parsonnet) and 66.3% (logEuroSCORE I). Thresholds were logEuroSCORE I 26%, EuroSCORE II 7%, STS 6%, Ambler 3%, and Parsonnet 19%. CONCLUSIONS: No risk evaluation system provided acceptable predictive ability. Scores derived from conventional cardiac surgery failed in risk prediction for TAVI. Specific risk tools are required. Until available, estimation of risk has to rely on judgment of an interdisciplinary heart team regarding individual patient factors.

Long-range DNA looping and gene expression analyses identify DEXI as an autoimmune disease candidate gene.

The chromosome 16p13 region has been associated with several autoimmune diseases, including type 1 diabetes (T1D) and multiple sclerosis (MS). CLEC16A has been reported as the most likely candidate gene in the region, since it contains the most disease-associated single-nucleotide polymorphisms (SNPs), as well as an imunoreceptor tyrosine-based activation motif. However, here we report that intron 19 of CLEC16A, containing the most autoimmune disease-associated SNPs, appears to behave as a regulatory sequence, affecting the expression of a neighbouring gene, DEXI. The CLEC16A alleles that are protective from T1D and MS are associated with increased expression of DEXI, and no other genes in the region, in two independent monocyte gene expression data sets. Critically, using chromosome conformation capture (3C), we identified physical proximity between the DEXI promoter region and intron 19 of CLEC16A, separated by a loop of >150 kb. In reciprocal experiments, a 20 kb fragment of intron 19 of CLEC16A, containing SNPs associated with T1D and MS, as well as with DEXI expression, interacted with the promotor region of DEXI but not with candidate DNA fragments containing other potential causal genes in the region, including CLEC16A. Intron 19 of CLEC16A is highly enriched for transcription-factor-binding events and markers associated with enhancer activity. Taken together, these data indicate that although the causal variants in the 16p13 region lie within CLEC16A, DEXI is an unappreciated autoimmune disease candidate gene, and illustrate the power of the 3C approach in progressing from genome-wide association studies results to candidate causal genes.

Valve-in-valve implantation of a novel and small self-expandable transcatheter heart valve in degenerated small surgical bioprostheses: the Hamburg experience.

BACKGROUND: Transcatheter valve-in-valve (VIV) implantation has emerged as a novel treatment option in patients with degenerated aortic bioprostheses and high surgical risk. However, VIV implantation in small aortic bioprostheses using first generation TAVI devices has frequently resulted in high postprocedural gradients and small effective orifice areas. Recently, an updated version of the self-expandable Medtronic CoreValve prosthesis, which is particularly suitable for small aortic annuli, has become available. We report on the feasibility and early results of VIV implantation using this novel device in a series of patients with degenerated small aortic bioprostheses. METHODS AND RESULTS: 16 patients from two Hamburg hospitals (age range 72-92 years) underwent implantation of a 23-mm CoreValve Evolut (Medtronic, Minneapolis, MN, USA) transcatheter heart valve into failing aortic bioprostheses with internal diameters below 21 mm. All patients were considered high risk for surgical aortic valve replacement after evaluation by an interdisciplinary heart team mean (logistic EuroSCORE range 9.0-88%). Implantation was successful without relevant remaining aortic regurgitation or signs of stenosis and a marked reduction in postprocedural gradientswas observed in 14 out of 16 patients. The mean gradient was reduced from from 34 mm Hg (SEM 10 mm Hg) to 14 mm Hg (SEM 6 mm Hg). No major device- or procedure-related adverse events occurred during 30-day follow up and clinical improvement was observed. CONCLUSIONS: Failing aortic bioprostheses with small internal diameters continue to be a challenging pathology for TAVI due to the risk of high residual gradients and small aortic orifice areas. This report provides first evidence that the 23-mm CoreValve Evolut, a novel self-expanding prosthesis, provides an improved treatment option in these specific patients due to its low profile which resulted in promising early results. © 2013 Wiley Periodicals, Inc.

Successful use of a left ventricular apical access and closure device for second-generation transapical aortic valve implantation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has become routine for the treatment of high-risk patients with aortic stenosis. We assessed safety and feasibility of a left ventricular apical access and closure device combined with second-generation transapical (TA) TAVI transcatheter heart valves (THV). METHODS AND RESULTS: Three elderly, comorbid patients (logEuroSCORE I 13.0-31.1%) received transapical aortic valve implantation (TA-AVI) via the Apica ASC device (Apica Cardiovascular Ltd., Galway, Ireland) using second-generation THV (Medtronic Engager [Medtronic 3F Therapeutics, Santa Ana, California, United States], JenaValve [JenaValve Technology GmbH, Munich, Germany], Symetis Acurate [Symetis S.A., Ecublens, Switzerland]). Access was gained using a non-rib-spreading technique and a novel access and closure device. THV deployment was successful with excellent hemodynamic outcome (no PVL, n = 2; trace PVL, n = 1; mean transvalvular gradients, 5-19 mm Hg) and complete apical hemostasis. No periprocedural major adverse events occurred and Valve Academic Research Consortium-2-defined composite end point of device success was met in all cases. CONCLUSION: Safety and feasibility of TA-AVI using the ASC device with second-generation THV was demonstrated. Combining latest available technology is a major step toward improved functional outcome and decreased surgical trauma in TA-AVI. Potentially, technical enhancements may eventually pave the way toward a fully percutaneous TA-AVI procedure.

Integrating genome-wide genetic variations and monocyte expression data reveals trans-regulated gene modules in humans.

One major expectation from the transcriptome in humans is to characterize the biological basis of associations identified by genome-wide association studies. So far, few cis expression quantitative trait loci (eQTLs) have been reliably related to disease susceptibility. Trans-regulating mechanisms may play a more prominent role in disease susceptibility. We analyzed 12,808 genes detected in at least 5% of circulating monocyte samples from a population-based sample of 1,490 European unrelated subjects. We applied a method of extraction of expression patterns-independent component analysis-to identify sets of co-regulated genes. These patterns were then related to 675,350 SNPs to identify major trans-acting regulators. We detected three genomic regions significantly associated with co-regulated gene modules. Association of these loci with multiple expression traits was replicated in Cardiogenics, an independent study in which expression profiles of monocytes were available in 758 subjects. The locus 12q13 (lead SNP rs11171739), previously identified as a type 1 diabetes locus, was associated with a pattern including two cis eQTLs, RPS26 and SUOX, and 5 trans eQTLs, one of which (MADCAM1) is a potential candidate for mediating T1D susceptibility. The locus 12q24 (lead SNP rs653178), which has demonstrated extensive disease pleiotropy, including type 1 diabetes, hypertension, and celiac disease, was associated to a pattern strongly correlating to blood pressure level. The strongest trans eQTL in this pattern was CRIP1, a known marker of cellular proliferation in cancer. The locus 12q15 (lead SNP rs11177644) was associated with a pattern driven by two cis eQTLs, LYZ and YEATS4, and including 34 trans eQTLs, several of them tumor-related genes. This study shows that a method exploiting the structure of co-expressions among genes can help identify genomic regions involved in trans regulation of sets of genes and can provide clues for understanding the mechanisms linking genome-wide association loci to disease.

Predictors and outcomes after transcatheter aortic valve implantation using different approaches according to the valve academic research consortium definitions.

OBJECTIVES: We report the results of a large single-center study evaluating predictors and outcomes after transcatheter aortic valve implantation (TAVI) with different devices and access routes according to the Valve Academic Research Consortium (VARC). BACKGROUND: The widespread adoption of TAVI warrants a systematic analysis of outcomes. Only few comprehensive data exist comparing different approaches as selected by a heart team. METHODS: TAVI was performed in 326 consecutive patients (mean age 80.6 ± 7.1 years, 55.5% female) at high risk for surgery with balloon-expandable and self-expanding devices through transfemoral or transapical access. Data were analyzed according to VARC endpoints; predictors of mortality were identified. RESULTS: All-cause mortality was 10.1% (30 days) and 29.9% (1 year) overall and comparable with regard to valve or access choice (P = 0.295) despite different risk profiles at baseline. Device success and 30-day safety endpoints were achieved in 87.1 and 21.2%. Myocardial infarction [hazard ratio (HR) 6.52], stage-2 and -3 acute kidney injury (HR 2.52 and 6.80) and major access site complications (HR 1.96) were independent predictors of 1-year all-cause mortality. Device success had a protective effect (HR 0.58). Baseline predictors included body mass index <20 kg/m(2) (HR 3.20), NYHA class IV (HR 1.87), left ventricular ejection-fraction <30% (HR 2.30), higher STS-PROM scores (HR 1.05 per percent), and age (group 75-85 years, HR 0.47). CONCLUSIONS: Comparable results were achieved with different devices and access routes in a heart team approach. Baseline and perioperative predictors of all-cause mortality were identified, contributing to the refinement of patient and device selection criteria for TAVI.

Patient gender does not affect outcome after transcatheter aortic valve implantation (TAVI).

BACKGROUND AND AIM OF THE STUDY: Female gender has recently been suggested to predict a beneficial outcome and lower mortality following transcatheter aortic valve implantation (TAVI). The study aim was to address gender differences in outcome following TAVI and potentially to replicate these findings. METHODS: The present single-center prospective registry of 326 patients with severe aortic stenosis treated by TAVI between 2008 and 2011 consisted of 181 women and 145 men. RESULTS: The procedural risk was not significantly different between men and women at baseline. For all-cause mortality no difference was observed at 30 days and at 12 months after TAVI. CONCLUSION: While several baseline characteristics between men and women treated by TAVI were shown to be different among the study population, no difference was observed in survival between both genders.

Genomewide association studies in cardiovascular disease--an update 2011.

BACKGROUND: Genomewide association studies have led to an enormous boost in the identification of susceptibility genes for cardiovascular diseases. This review aims to summarize the most important findings of recent years. CONTENT: We have carefully reviewed the current literature (PubMed search terms: "genome wide association studies," "genetic polymorphism," "genetic risk factors," "association study" in connection with the respective diseases, "risk score," "transcriptome"). SUMMARY: Multiple novel genetic loci for such important cardiovascular diseases as myocardial infarction, hypertension, heart failure, stroke, and hyperlipidemia have been identified. Given that many novel genetic risk factors lie within hitherto-unsuspected genes or influence gene expression, these findings have inspired discoveries of biological function. Despite these successes, however, only a fraction of the heritability for most cardiovascular diseases has been explained thus far. Forthcoming techniques such as whole-genome sequencing will be important to close the gap of missing heritability.

Transfemoral TAVI using the self-expanding ACURATE neo prosthesis: one-year outcomes of the multicentre "CE-approval cohort".

AIMS: The aim of this study was to assess the safety and performance of the ACURATE neo transcatheter heart valve and its transfemoral delivery system. METHODS AND RESULTS: The prospective, multicentre "CE-approval cohort" consists of a prospective series of the first 89 patients implanted with the ACURATE neo prosthesis. The primary endpoint was all-cause mortality at 30 days. Mean patient age was 83.7±4.4 years and logistic EuroSCORE I was 26.5±7.7%. Procedural success was obtained in 84 patients (94.4%). At 30 days, three patients had died, and two major strokes and one reintervention for a ventricular septal defect occurred, leading to a major adverse cardiac and cerebrovascular event (MACCE) rate of 6.7%. Eight patients (10.3%) received a permanent pacemaker. At one year, 20 patients (22.5%) had died and the MACCE rate was 27%. Effective orifice area was 1.76±0.34 cm2, and mean gradient 7.5±2.8 mmHg. Only three patients (4.5%) had moderate paravalvular regurgitation. NYHA Class III/IV was present in 94.4% of patients at baseline, in 9.9% at 30 days and in 4.5% at one year post procedure. CONCLUSIONS: This first-in-human experience with a novel self-expanding heart valve showed low rates of procedural mortality, major stroke and pacemaker implantation, and good performance outcomes.

Single-centre experience with next-generation devices for transapical aortic valve implantation.

OBJECTIVES: Transcatheter aortic valve implantation (TAVI) has become an established procedure in patients with aortic stenosis and high surgical risk. Experience with first-generation transcatheter heart valves (THVs) is broad but limitations, e.g. paravalvular regurgitation, have been demonstrated. Much hope rests on the recently Conformité Européenne mark approved next-generation devices to improve results in these patients. However, apart from the initial approval studies, clinical data with these new devices are still scarce. We aimed to assess short-term outcomes of 200 consecutive patients who underwent transapical TAVI with next-generation THV at our institution. METHODS: Transapical TAVI was performed in 200 consecutive patients 80.5±6.7 years old (38.5% female) at high surgical risk (log EuroSCORE 20.2±16.5%). Devices implanted were the Engager (Medtronic, Inc., Minneapolis, MN, USA; n=50), JenaValve (JenaValve Technology, Munich, Germany; n=88) and Symetis Acurate (Symetis SA, Ecublens, Switzerland; n=62) THV that were selected by the heart team on an individual basis. Data at baseline, during the procedure and follow-up were analysed according to standardized Valve Academic Research Consortium end points. Median follow-up was 219 days. RESULTS: Implantation was successful in 96.5% of cases. Valve function improved significantly with an increase in effective orifice area from 0.8±0.4 to 1.8±0.3 cm2 and a reduction in mean transvalvalvular gradients from 34.0±17.0 to 11.2±5.4 mmHg. Paravalvular regurgitation was none or trace in 70.3% of patients, Grade 1 in 26.1%, and Grade 2 in 3.5%. No patients developed aortic regurgitation>Grade 2. Major access site complications occurred in 6.5%, major stroke in 1.5% and stage-3 kidney injury in 2.5% of patients. A permanent pacemaker was implanted in 20.5% of patients overall and in 8.0% for a complete heart block. At 30-day follow-up 72.8% of patients were in New York Heart Association class I or II (10.5% at baseline). Overall survival was 91.5% at 30 days and 73.9% at 1 year. CONCLUSIONS: In a real-world clinical setting, next-generation transapical THV yielded positive haemodynamic results. The incidence of relevant paravalvular regurgitation was scarce in this group and clinical outcomes were encouraging during short-term follow-up. Long-term follow-up is required to investigate the durability of these new devices.

Transfemoral TAVI without pre-dilatation using balloon-expandable devices: a case-matched analysis.

OBJECTIVES: This comparative case-matched analysis investigated feasibility and safety of direct transfemoral (TF) transcatheter aortic valve implantation (TAVI) without pre-dilatation using balloon-expandable devices. BACKGROUND: Presently, balloon aortic valvuloplasty (BAV) is considered mandatory preceding transfemoral TAVI with balloon-expandable devices. However, procedural severe adverse events may be associated with BAV. METHODS: 26 consecutive patients (study group) received direct TF-TAVI using Edwards Sapien XT (n = 17) or Sapien 3 (n = 9) devices (61.5% female, 81.3 ± 6.3 years, logEuroSCORE I 15.3 ± 13.2%). A control group of patients after conventional TF-TAVI was retrieved from our database containing 1153 TAVI patients and matched to the study group regarding baseline and procedural data. Data reporting adheres to VARC-2 definitions. RESULTS: Device success was 96.2% (25/26) and 92.3% (24/26) in study and control groups, respectively (p = 1.00). Procedure time (60.0 ± 54.0 vs. 70.0 ± 29.1 min; p = 0.41), fluoroscopy time (13.3 ± 5.8 vs. 17.8 ± 6.9 min; p = 0.01) and amount of contrast agent (118.7 ± 47.9 vs. 153.0 ± 53.2 ml; p = 0.02) were lower in the study group. All-cause 30-day mortality was 7.7% (2/26) in both groups, disabling stroke was observed in 3.8% (1/26) and 7.7% (2/26) in study and control groups, respectively. Resultant transvalvular mean gradient and effective orifice area (EOA) were 11 ± 5 vs. 11 ± 5 mmHg and 1.6 ± 0.3 vs. 1.5 ± 0.3 cm(2). Paravalvular leakage ≥ grade II was observed in 0 and 7.7% (2/26; p = 0.49). CONCLUSIONS: TF-TAVI without pre-dilatation was feasible and safe in this consecutive series of patient regardless of aortic valve morphology, for example. extent of valvular calcification or baseline EOA. This technique resulted in significantly lower fluoroscopy times and amounts of contrast agent while yielding non-inferior hemodynamic and clinical outcome.

Transapical transcatheter aortic valve implantation without prior balloon aortic valvuloplasty: feasible and safe.

OBJECTIVES: Currently, preimplant balloon aortic valvuloplasty (BAV) is considered a prerequisite for successful subsequent transapical transcatheter aortic valve implantation (TA-TAVI) using balloon-expandable devices. However, cerebral embolization has been shown to originate at least in part from BAV procedures. Omitting BAV may therefore reduce neurological events after TAVI and facilitate the procedure while yielding non-inferior haemodynamic and clinical outcomes. METHODS: From May 2011 through December 2012, a total of 50 consecutive patients were treated by TA-TAVI without preimplant BAV (TA-TAVI(-BAV), study group) using the Edwards Sapien XT device (54% male, age 78 ± 8 years, logistic European System for Cardiac Operative Risk Evaluation I 21 ± 14%). Data were prospectively entered into a dedicated database, retrospectively analysed and compared with a consecutive series of conventional TA-TAVI using the same device (control group, n = 50). Reporting of data followed Valve Academic Research Consortium definitions. RESULTS: Overall device success rate was 94% (47/50) and 86% (43/50) in study and control groups, respectively (P = 0.32). Procedure time was similar in the study group compared with the control group (88 ± 31 vs 91 ± 25 min, P = 0.60), while significantly less contrast was used (138 ± 68 vs 183 ± 78 ml, P < 0.001). Post-procedural peak and mean transvalvular gradients were 16 ± 7 and 8 ± 3 mmHg, respectively, in the study group with similar values in the control group (19 ± 9 and 9 ± 5 mmHg, P = 0.08 and P = 0.09, respectively). Residual paravalvular leakage (PVL) grade 2 was present in 2 and 8% in study and control groups, respectively (P = 0.36), with no PVL >grade 2 in any patient. Rates of 30-day mortality and periprocedural stroke were 4 and 10% (P = 0.44) and 2 and 6% (P = 0.62), respectively. CONCLUSIONS: TA-TAVI(-BAV) is feasible and safe and has become ur default technique for patients allocated to TA-TAVI with balloon-expandable devices. This approach resulted in less contrast agent used and facilitated the procedure without compromising valve performance. Possible beneficial effects of this approach on the incidence of cerebrovascular events, other periprocedural complications or haemodynamic valve performance need to be verified in larger patient numbers before general recommendations can be made.

Correction of acquired von Willebrand syndrome by transcatheter aortic valve implantation.

AIMS: Acquired von Willebrand syndrome (aVWS) is a common complication of severe aortic valve stenosis and can be corrected by surgical valve replacement. Transcatheter aortic valve implantation (TAVI) is gaining importance, but the influence of this new technique on aVWS has never been examined. The objective of this study was to assess the impact of TAVI on aVWS. METHODS: We enrolled 15 patients with severe aortic stenosis and high surgical risk admitted for elective TAVI. All patients were successfully treated by TAVI, using either the transfemoral (n = 6) or transapical approach (n = 9). Patients were screened for aVWS by measuring PFA-100 in vitro closure time, von Willebrand factor (VWF) antigen, VWF function, and VWF multimer analysis. Analyses were then repeated 30 minutes, 24 hours, and 7 days after valve replacement. RESULTS: Fourteen of 15 patients showed pathologic alterations of VWF. An inverse correlation was observed between the transvalvular pressure gradient and VWF high-molecular-weight multimers (VWF:HMWM) (r = -0.621; P=.01), which are essential for the platelet dependent hemostatic function of VWF. Transaortic gradient was significantly reduced in all patients following TAVI. Hemostaseologic findings improved in all patients following TAVI, the percentage of VWF:HMWM increased (19.05 ± 5.19% before TAVI to 24.08 ± 4.75% (P=.04) on day 7 post TAVI), and the multimer pattern normalized. CONCLUSIONS: Acquired von Willebrand syndrome due to aortic valve stenosis can successfully be corrected by TAVI.

The challenge of valve-in-valve procedures in degenerated Mitroflow bioprostheses and the advantage of using the JenaValve transcatheter heart valve.

AIMS: Recently, the feasibility of valve-in-valve procedures using current first-generation transcatheter heart valves (THV) in cases of structural valve degeneration has been reported as an alternative to conventional open repeat valve replacement. By design, certain biological valve xenografts carry a high risk of coronary ostia occlusion due to lateral displacement of leaflets after valve-in-valve procedures. In the present report we aimed to prove feasibility and safety of transapical valve-in-valve implantation of the JenaValve THV in two cases of degenerated Mitroflow bioprostheses. METHODS AND RESULTS: We herein report two cases of successful transapical valve-in-valve procedures using a JenaValve THV implanted in Sorin Mitroflow bioprostheses for structural valve degeneration. Both patients were alive and in good clinical condition at 30 days from the procedure. However, increased transvalvular gradients were noted in both cases. CONCLUSIONS: Transcatheter valve-in-valve implantation of a JenaValve THV is a valid alternative for patients with degenerated Mitroflow bioprostheses of sufficient size and in the presence of short distances to the coronary ostia who are too ill for conventional repeat open heart surgery. Increased pressure gradients have to be expected and weighed against the disadvantages of other treatment options when planning such a procedure.

Edwards Sapien XT valve placement as treatment option for aortic regurgitation after transfemoral CoreValve implantation: a multicenter experience.

UNLABELLED: Transcatheter aortic valve replacement (TAVI), though a preferred treatment option in the elderly population carrying increased risks for open heart surgery, may result in prognosis-limiting moderate or severe aortic regurgitation. Here, we report a series of 11 patients from 3 German TAVI centers, suffering from moderate- to high-grade aortic regurgitation after CoreValve implantation, who were subsequently treated by Edwards Sapien XT implantation. METHODS: The patients were 79.5 ± 4.2 years of age and presented between November 2009 and February 2013 with a symptomatic high-grade aortic stenosis (mean maximum gradient 57 ± 22 mmHg) and EuroSCORE of 16 ± 7%. Initial implantation of a Medtronic CoreValve resulted in moderate-to-severe aortic regurgitation (grade 2.64 ± 0.37) although postdilatation was attempted in eight cases and snare repositioning was attempted in one case. RESULTS: All 11 patients were treated by a Sapien XT (Edwards) valve implanted into the initially deployed CoreValve: four via transfemoral, one via transaortical and six via transapical approaches. Successful implantation was possible in all 11 patients resulting in a reduction of aortic regurgitation to mean grade 0.23 ± 0.39. Two patients required permanent pacemaker. After 30 days, ten patients were alive, whereas one patient succumbed to pneumonia complicating advanced chronic obstructive pulmonary disease. CONCLUSION: In the instance of moderate or severe aortic regurgitation after TAVI of a CoreValve, transfemoral or transapical Sapien XT valve-in-valve deployment is an excellent option to reduce residual regurgitation to none or mild.