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BACKGROUND: Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) is superior to angiography-guided PCI. The clinical uptake of FFR has been limited, however, by the need to advance a wire in the coronary artery, the additional time required and the need for hyperaemic agents which can cause patient discomfort. FFR derived from routine coronary angiography eliminates these issues. AIMS: The aim of this study was to assess the diagnostic performance and accuracy of three-dimensional quantitative coronary angiography (3D-QCA)-based vessel FFR (vFFR) compared to pressure wire-based FFR (≤0.80). METHODS: The FAST II (Fast Assessment of STenosis severity) study was a prospective observational multicentre study designed to evaluate the diagnostic accuracy of vFFR compared to the reference standard (pressure wire-based FFR ≤0.80). A total of 334 patients from six centres were enrolled. Both site-determined and blinded independent core lab vFFR measurements were compared to FFR. RESULTS: The core lab vFFR was 0.83±0.09 and pressure wire-based FFR 0.83±0.08. A good correlation was found between core lab vFFR and pressure wire-based FFR (R=0.74; p

Protein pool turnover is a critically important cellular homeostatic component, yet it has been little explored in the context of heart failure (HF) pathophysiology. We employed in vivo 2H labeling/ proteome dynamics for non-biased discovery of turnover alterations involving functionally linked cardiac and plasma proteins in canine tachypacing-induced HF, an established preclinical model of dilated cardiomyopathy. Compared to control, dogs with congestive HF displayed bidirectional turnover changes of 28 cardiac proteins, i.e. reduced half-life of several key enzymes involved in glycolysis, homocysteine metabolism and glycogenesis, and increased half-life of proteins involved in proteolysis. Changes in plasma proteins were more modest: only 5 proteins, involved in various functions including proteolysis inhibition, hemoglobin, calcium and ferric-iron binding, displayed increased or decreased turnover rates. In other dogs undergoing cardiac tachypacing, we infused for 2 weeks the myokine Follistatin-like protein 1 (FSTL1), known for its ameliorative effects on HF-induced alterations. Proteome dynamics proved very sensitive in detecting the partial or complete prevention, by FSTL1, of cardiac and plasma protein turnover alterations. In conclusion, our study unveiled, for the first time in a large mammal, numerous HF-related alterations that may serve as the basis for future mechanistic research and/or as conceptually new molecular markers.

To assess the feasibility and safety of minimal-contrast percutaneous coronary intervention (PCI) using rotational atherectomy (RA) in patients with severe coronary calcification at high-risk of contrast-associated acute kidney injury (AKI). Twenty-six patients with advanced chronic kidney disease undergoing PCI with RA at three high-volume centres were included. Baseline intravascular ultrasound (IVUS) was performed to assess lesion morphology, and to guide burr-, balloon-, and stent-selection. Final result was assessed by IVUS and angiographically. Feasibility and safety were determined by procedural and in-hospital complications, and efficacy was assessed by freedom from contrast-associated AKI after PCI. Procedural and in-hospital outcome was compared to a propensity-matched population of standard RA PCI. Mean glomerular filtration rate was 32 ± 17 ml/min/1.73 m2. In seven cases PCI was performed in the setting of acute coronary syndrome. The left main coronary artery was treated in 27.8% and a two-stent bifurcation technique in 44.4%. RA was more often performed electively compared to the standard RA cohort (92.3 vs. 50%; p = 0.0016). Angiographic success was achieved in 100% and documented with a median contrast amount of 12.5 ml [Range 4–43]. No in-hospital death or myocardial infarction was reported. Contrast-associated AKI occurred in one patient versus five patients in standard RA group (p = 0.19). Shorter fluoroscopy time and lower radiation dose were achieved as compared to standard RA. A minimal-contrast RA approach with IVUS-guidance for treatment of complex calcified coronary lesions is feasible and safe with high success rate.

Background: Transcatheter aortic valve replacement (TAVR) has become the standard of care in the majority of patients with symptomatic severe aortic stenosis. Data on long-term mortality and durability of transcatheter heart valves (THVs) beyond 5 years are limited. Our study aimed to assess elderly and high-risk patients’ long-term outcomes treated with TAVR in a prospective single-centre registry focusing on the durability of THVs. Methods: We included 795 patients with severe calcific aortic stenosis treated by transfemoral TAVR between 2006 and 2011. Echocardiography was performed at baseline; discharge; 1 year; and afterward, annually, until the longest available follow-up. Mortality rates were estimated for 1, 5, 6, 7, and 8 years. The rates of structural valve deterioration (SVD) and bioprosthetic valve failure (BVF) were assessed in accordance with consensus definitions. Outcome measures were adjudicated according to Valve Academic Research Consortium-2 (VARC-2). Results: Median (interquartile range) follow-up time was 1345 (316; 2015) days. One-year, 5-year, 6-year, 7-year, and 8-year overall mortality was 25.4%, 59.0%, 64.6%, 67.9%, and 69.2%, respectively. At 8 years, no significant differences in mortality were found comparing self-expanding vs balloon-expandable valves (69.5% vs 68.0%, P = 0.709) and postdilatation (PD) vs no-PD (69.4% vs 69.2%, P = 0.363). SVD was detected in 26 patients (3.3%), and 19 (2.4%) of the 795 patients had evidence of BVF during follow-up. Conclusions: Our study demonstrates good long-term results for high-risk patients who were alive up to 8 years after TAVR. Résumé: Contexte: Le remplacement valvulaire aortique par cathéter (RVAC) est maintenant la norme de soins dans la majorité des cas de sténose de l’aorte grave symptomatique. On dispose de peu de données sur la mortalité à long terme et sur la durabilité des valves cardiaques transcathéter (VCT) au-delà de 5 ans. Nous avons donc évalué les résultats à long terme, notamment la durabilité des VCT, chez les patients âgés et les patients exposés à un risque élevé traités par RVAC figurant dans un registre prospectif unicentrique. Méthodologie: Notre étude comprenait 795 patients présentant une sténose calcifiée de l’aorte grave traitée par RVAC transfémoral entre 2006 et 2011. Une échocardiographie a été réalisée au départ, à la sortie de l’hôpital, 1 an plus tard et tous les ans par la suite, jusqu’au suivi le plus long disponible. Les taux de mortalité à 1, 5, 6, 7 et 8 ans ont été estimés. Les taux de détérioration structurelle des valves (DSV) et de défaillance de la bioprothèse valvulaire (DBV) ont été évalués selon des définitions établies par consensus. Les mesures des résultats ont été confirmées selon les critères du VARC-2 (Valve Academic Research Consortium-2). Résultats: La durée médiane (intervalle interquartile) du suivi était de 1 345 (316 à 2 015) jours. Les taux de mortalité globaux s’établissaient comme suit : taux à 1 an : 25,4 %; à 5 ans : 59,0 %; à 6 ans : 64,6 %; à 7 ans : 67,9 % et à 8 ans : 69,2 %. À 8 ans, on n’a noté aucune différence significative en ce qui concerne la mortalité chez les patients ayant reçu une valve auto-expansible comparativement à ceux ayant reçu une valve expansible par ballonnet (69,5 % vs 68,0 %; p = 0,709) et chez ceux ayant subi une post-dilatation ou non (69,4 % vs 69,2 %; p = 0,363). Une DSV a été détectée chez 26 patients (3,3 %), et 19 (2,4 %) des 795 patients ont présenté des signes de DBV pendant la période de suivi. Conclusions: Notre étude a révélé de bons résultats à long terme chez les patients présentant un risque élevé qui étaient toujours en vie 8 ans après le RVAC.

Background Data about the impact of left-atrial appendage thrombosis (LAAT) on early safety and mortality in patients undergoing transfemoral transcatheter aortic valve implantation (TF-TAVI) are scarce. We aimed to investigate the prevalence and predictors of LAAT and the outcome associated with this condition in patients treated by TF-TAVI. Methods Retrospective data analysis was derived from a prospective single-centre registry comparing patients with and without LAAT regarding early safety at 30 days, according to Valve Academic Research Consortium-2 (VARC-2) and 2-year mortality. Results LAAT was found in 7.6% of the whole cohort (n = 2527) and in 16.6% in those patients with known pre-existing atrial fibrillation (AF cohort, n = 1099). Compared with controls, patients with LAAT were sicker, indicated by a higher Society of Thoracic Surgeons (STS) score and burden of comorbidities. Neither VARC-2–defined early safety at 30 days nor the rate of stroke was different between LAAT and controls in both the whole (early safety: 29.2% vs 24.2%, P = 0.123; stroke: 5.9% vs 4.7%, P = 0.495) and AF cohort (early safety: 29.1% vs 22.9%, P = 0.072; stroke: 5.6% vs 3.3%, P = 0.142). Evaluating the whole cohort in a univariate analysis, the 2-year mortality was significantly higher in LAAT compared with controls (hazard ratio, 1.41; 95% confidence interval, 1.07-1.86; P = 0.014). However, multivariate analysis of the whole cohort and the AF cohort revealed no association between LAAT and 2-year mortality. Conclusions LAAT was frequent in patients undergoing TF-TAVI— in particular, in patients with histories of AF—but it was not associated with an increase in periprocedural complications and did not predict 2-year mortality.

Background: Restenosis after endovascular interventions is a clinically relevant process that is directly associated with increased morbidity. Thereby, an increased migration and proliferation of vascular smooth muscle cells (VSMCs) is mainly responsible for recurrent lumen narrowing. Previously, we showed that caveolin‑1 (Cav‑1) and endothelial nitric oxide synthase (eNOS) were directly involved in neointimal proliferation. Aims: In the current study, we investigated the impact of Cav‑1 and eNOS on adventitial processes in a murine model. Methods: Denuded aortas from C57Bl6n (wild‑type [WT]), Cav‑1-/, eNOS-/, and Cav‑1-//eNOS-/ mice were transplanted into common carotid arteries of WT mice. The explantation was performed after 6 weeks, followed by Elastica van Gieson staining and immunohistochemistry. Results: The Cav‑1-/ and the eNOS-/ aortas showed an increase in the adventitial content of macrophages, whereas their combined knockout did not lead to additive effects. Differences were observed despite the same acceptor, suggesting the local origin of inflammatory cells. Furthermore, the WT transplants exhibited the highest content of vascular endothelial growth factor A (VEGF‑A) despite the lowest macrophage content. In contrast, the knockout aortas showed a decreased content of VEGF‑A as well as decreased expression of α-smooth muscle actin (α­‑SMA) in the tunica media, suggesting induced VSMC migration. Moreover, the WT aortas exhibited increased neovessel formation. Conclusions: Cav‑1 and eNOS inhibit adventitial macrophage‑derived inflammation and modulate its cellular function. The knockout of Cav‑1 and eNOS leads to a decreased expression of VEGF-A, with decreased neovessel formation and increased migration of VSMCs, which promote a proatherogenic phenotype.

The use of bioprostheses for surgical aortic valve replacement increased substantially within the last years. In case of prosthesis failure, re-SAVR is standard of care, whereas valve-in-valve deployment of a transfemoral transcatheter aortic valve prosthesis (VinV-TFAVI) has recently emerged as an alternative. We sought to evaluate early safety, clinical efficacy, and all-cause 1-year-mortality of VinV-TFAVI and redo surgery for failing aortic bioprostheses (re-SAVR).Patients receiving either VinV-TFAVI (n = 147) or re-SAVR (n = 111) for a degenerated aortic bioprosthesis between 01/2006 and 05/2017 were included in this analysis. All-cause 1-year mortality was the primary outcome measure. Early safety and clinical efficacy according to VARC-2 endpoint definitions were evaluated at 30 days. Baseline characteristics differed significantly between both groups including age, STS-PROM, and incidence of relevant comorbidities. Re-stenosis was the predominant mode of failure in 45.9% of re-SAVR and 63.1% of VinV-TFAVI patients. The rate of "early safety" endpoints was lower with VinV-TFAVI (17.7% vs. 64.9%, p 0.01), the rate of "clinical efficacy" endpoints was lower, e.g. better with re-SAVR (53.1% vs. 32.4%, p 0.01). All-cause 1-year-mortality (VinV-TFAVI 8.8% vs re-SAVR 9.9%, p = 0.84) was not different. Treatment strategy was not associated with 1-year-mortality in a Cox regression analysis. The incidence of prosthesis-patient-mismatch was higher in VinV-TFAVI compared to re-SAVR.VinV-TFAVI represents a viable alternative for treatment of degenerated aortic bioprostheses in patients at increased surgical risk. However, in patients at low risk for reoperation, a better clinical efficacy and acceptable safety may favour re-SAVR.

Diabetes mellitus (DM) is a risk factor for cardiovascular disease. However, its effect on procedural and follow-up performance after transcatheter aortic valve replacement (TAVR) remains controversial. We performed an observational study of all consecutive patients treated with a transfemoral TAVR in a single-center cohort (n = 1818). All patients were stratified by diabetes status and gender. All-cause 3-year mortality was the primary endpoint. Male patients with DM were identified to have substantially increased 3-year mortality [125/314 (39.8%)] compared to males without DM [142/478 (29.7%), p

Childhood obesity is associated with changes in myocardial geometry and function indicating early onset of unfavorable alterations of the myocardium [(1,2)][1]. The value of those studies is limited by a cross-sectional study design. We aimed to assess the impact of weight reduction on temporal

Background Patients undergoing transcatheter aortic valve replacement (TAVR) are often characterized by risk factors not reflected in conventional risk scores. In this context, little is known about the outcome of patients suffering from an active cancer disease (ACD). The objective was to determine the prevalence, clinical characteristics, perioperative outcomes, and mortality of patients with ACD undergoing TAVR compared to those with a history of cancer (HCD) and controls without known tumor disease. Methods TAVR patients between 02/2006 and 09/2014 were stratified according to the presence of ACD, HCD, and control. All-cause-mortality at 1-year was the primary end point. All end point definitions were subject to the Valve Academic Research Consortium II definitions. Results Overall, 1821 patients were included: 99 patients (5.4%) suffered from ACD and 251 patients (13.8%) had HCD. ACD was related to a solid organ or hematological source in 72.7% and 27.3%, respectively. Patients with ACD were more often male (P = 0.004) and had a lower logisticEuroScore I (P = 0.033). Overall rates of VARC-II defined periprocedural myocardial infarction, stroke, bleeding, access-site complications, and acute kidney injury were not different between groups. Thirty-day mortality did not differ between patients with ACD, HCD, and controls (6.1% vs 4.4% vs 7.6%, P = 0.176). All-cause 1-year mortality was higher in patients with ACD compared HCD and controls (37.4% vs 16.4% vs 20.8%, P

Neurological complications after transcatheter aortic valve replacement (TAVR) may be reduced with transcatheter cerebral embolic protection (TCEP).This study evaluated the safety and efficacy of TCEP during TAVR.Nineteen centers randomized 363 patients undergoing TAVR to a safety arm (n = 123), device imaging (n = 121), and control imaging (n = 119). The primary safety endpoint consisted of major adverse cardiac and cerebrovascular events (MACCE) at 30 days, and the primary efficacy endpoint was reduction in new lesion volume in protected brain territories on magnetic resonance imaging scans at 2 to 7 days. Patients underwent neurocognitive assessments, and the debris captured was analyzed.The rate of MACCE (7.3%) was noninferior to the performance goal (18.3%, pTCEP was safe, captured embolic debris in 99% of patients, and did not change neurocognitive function. Reduction in new lesion volume on magnetic resonance scans was not statistically significant. (Cerebral Protection in Transcatheter Aortic Valve Replacement [SENTINEL]; NCT02214277).

OBJECTIVES To evaluate the impact of previous coronary artery bypass grafting (CABG) on early safety at 30 days and 1-year mortality in patients receiving transcatheter aortic valve replacement (TAVR). BACKGROUND The use of TAVR in patients with previous CABG suffering from severe aortic stenosis has increased in the last years. METHODS Consecutive TAVR patients were stratified according to previous CABG versus no previous cardiac surgery (control). All-cause 1-year mortality and early safety at 30 days were evaluated. RESULTS In the unmatched cohort and compared to control (n = 2,364), CABG (n = 260) were younger, more often male and suffered more often from comorbidities leading to an increased STS-score (p

Introduction Data about the impact of left atrial appendage thrombosis (LAAT) on early safety and midterm mortality in patients undergoing transfemoral (TF) transcatheter aortic valve implantation (TAVI) are scarce. Purpose To investigate the incidence and predictors of LAAT as well as the outcome associated with this condition in a large cohort of patients treated by TF-TAVI. Methods Patients receiving TF-TAVI for native aortic valve stenosis or failed aortic bioprostheses were stratified according to the presence of LAAT diagnosed by transoesophageal echocardiography. Early safety at 30-days according to Valve Academic Research Consortium-2 (VARC-2) and 2-year all-cause mortality were the primary outcome measures. Results From 02/2006 to 06/2016, 2.527 patients (88.5%) out of 2.854 patients treated by TF-TAVI had an available transesophageal echocardiography (TEE) at baseline and formed the analysis cohort. LAAT was found in 7.6% of the whole cohort and in 16.6% in those patients with known pre-existing atrial fibrillation (AF cohort). Patients with LAAT appeared to be sicker compared to controls indicated by a higher STS-Score and burden of comorbidities. Neither VARC-2 defined early safety at 30-days nor the rate of stroke was different between LAAT and controls in both the whole (early safety: 24.2% vs. 29.2%, p=0.123; stroke: 4.7% vs. 5.9%, p=0.495) and AF cohort (early safety: 22.9% vs. 29.1%, p=0.072; stroke: 3.3% vs. 5.6%, p=0.142). Evaluating the whole cohort in a univariate analysis, the 2-year mortality was significantly higher in LAAT compared to controls (HR 1.41 [95% CI 1.07–1.86], p=0.014). However, a multivariate analysis of the whole cohort and a separate examination of the AF cohort revealed no association between LAAT and 2-year mortality. Conclusion LAAT was frequent in patients undergoing TF-TAVI, in particular in patients with a history of AF, but it was not associated with an increase in periprocedural complications. The fact that LAAT was no independent predictor of mortality indicates that it should be interpreted as a marker of an advanced disease stage rather than a prognostic factor.

Dilated cardiomyopathy (DCM) is a myocardial disease of dogs and humans characterized by progressive ventricular dilation and depressed contractility and it is a frequent cause of heart failure. Conventional pharmacological therapy cannot reverse the progression of the disease and, in humans, cardiac transplantation remains the only option during the final stages of heart failure. Cytoprotective gene therapy with vascular endothelial growth factor-B167 (VEGF-B167) has proved an effective alternative therapy, halting the progression of the disease in experimental studies on dogs. The aim of this work was to test the tolerability and feasibility of intracoronary administration, under fluoroscopic guidance, of VEGF-B167 carried by adeno-associated viral vectors in canine DCM patients. Ten patients underwent the gene delivery procedure. The intraoperative phase was well tolerated by all dogs. Clinical and echocardiographic assessments at 7- and 30-days post-procedure showed stable conditions compared to the pre-procedure phase. The results of this work indicate that intracoronary VEGF-B167 gene delivery is feasible and tolerated in dogs with DCM. Further monitoring/investigations are ongoing to evaluate the effects of this therapy on disease progression.

Purpose This study aimed to investigate baseline, exercise testing, and exercise training-mediated predictors of change in peak oxygen uptake (V˙O2peak) from baseline to 12-wk follow-up (ΔV˙O2peak) in a post hoc analysis from the SMARTEX Heart Failure trial. Methods We studied 215 patients with heart failure with left ventricular ejection fraction (LVEF) ≤35%, and New York Heart Association (NYHA) classes II-III who were randomized to either supervised high-intensity interval training with exercise target intensity of 90%-95% of peak heart rate (HRpeak) or supervised moderate continuous training (MCT) with target intensity of 60%-70% of HRpeak, or who received a recommendation of regular exercise on their own. Predictors of ΔV˙O2peak were assessed in two models: a logistic regression model comparing highest and lowest tertiles (baseline parameters) and a multivariate linear regression model (test/training/clinical parameters). Results The change in V˙O2peak in response to the interventions (ΔV˙O2peak) varied substantially, from -8.50 to +11.30 mL·kg·min. Baseline NYHA (class II gave higher odds vs III; odds ratio (OR), 7.1 (2.0-24.9); P = 0.002), LVEF (OR per percent, 1.1 (1.0-1.2); P = 0.005), and age (OR per 10 yr, 0.5 (0.3-0.8); P = 0.003) were associated with ΔV˙O2peak.In the multivariate linear regression, 34% of the variability in ΔV˙O2peak was explained by the increase in exercise training workload, ΔHRpeak between baseline and 12-wk posttesting, age, and ever having smoked. Conclusion Exercise training response (ΔV˙O2peak) correlated negatively with age, LVEF, and NYHA class. The ability to increase workload during the training period and increased ΔHRpeak between baseline and the 12-wk test were associated with a positive outcome.

Objectives This study sought to evaluate SAPIEN 3 (S3) (Edwards Lifesciences, Irvine, California) positioning using different strategies. Background Aortic valve-in-valve (ViV) is associated with high risk of elevated gradients. Methods S3 aortic ViV procedures in stented bioprostheses were studied. Transcatheter heart valve (THV) positioning was analyzed in a centralized core lab blinded to clinical outcomes. A combined endpoint of severely elevated mean gradient (≥30 mm Hg) or pacemaker need was established. Two positioning strategies were compared: central marker method and top of S3 method. Optimal final depth was defined as S3 depth ≤20%. Results A total of 113 patients met inclusion criteria and were analyzed (76.5 ± 9.7 years of age, 65.8% male, STS score 8 ± 7.6%). THVs had incomplete shortening in comparison to fully expanded valves (92 ± 3.4%), and expansion was more complete in optimal positioning cases compared with others (93.2 ± 2.7% vs. 91.5 ± 3.5%; p = 0.027). The central marker method demonstrated greater correlation with final implantation depth than the top of S3 method (R2 of 0.48 and 0.14; p Conclusions Optimal S3 positioning in aortic ViV is associated with better outcomes. Central marker positioning is more reliable than top of S3 positioning. Central marker bottom position should be 3 mm to 6 mm above the ring.

Objectives Assessment of aortic regurgitation (AR) immediately after transcatheter aortic valve replacement (TAVR) is essential to guide further intervention in cases of relevant AR. It was the aim of this study to identify a simple and reproducible hemodynamic parameter for the assessment of AR. Background Relevant AR after TAVR is present in up to 21% of cases and might be associated with adverse long-term outcomes. Methods Three hundred sixty-two consecutive patients who were treated with TAVR for symptomatic aortic valve stenosis were analyzed. AR was assessed by aortic root angiography according to the Sellers classification. For hemodynamic evaluation, the diastolic pressure-time (DPT) index was calculated after TAVR: the area between the aortic and left ventricular pressure-time curves was measured during diastole and divided by the duration of diastole to calculate the DPT index. The DPT index was finally adjusted for the respective systolic blood pressure: DPT indexadj = (DPT index/systolic blood pressure) × 100. Results Patients with angiographically nonrelevant AR (grade 27.9: 41.4% versus 13.5% (hazard ratio: 3.8; 95% confidence interval: 2.4 to 5.9; p [log rank-test] < 0.001). In multivariate regression analysis, DPT indexadj ≤27.9 was the strongest independent predictor of 1-year mortality (hazard ratio: 2.5; 95% confidence interval: 1.8 to 3.7; p < 0.001). Conclusions DPT indexadj is a simple, investigator-independent parameter that should be considered to differentiate between relevant and nonrelevant AR after TAVR.

The role of continued versus interrupted oral anticoagulation (OAC) in patients with atrial fibrillation (AF) who underwent transfemoral transcatheter aortic valve implantation (TF-TAVI) for severe aortic stenosis is uncertain. The aim of this retrospective investigation was to evaluate the impact (1) of continued versus interrupted OAC on early safety and (2) of postoperative anticoagulant management on the 1-year mortality in patients with AF who underwent TF-TAVI. Consecutive patients with AF and on OAC at admission (n = 598) were stratified according to interrupted (iVKA) versus continued vitamin K antagonist (cVKA) versus continued direct oral anticoagulants (DOAC) at the time of TF-TAVI. Valve Academic Research Consortium-2 early safety was the primary outcome measure. Patients with iVKA (n = 299), cVKA (n = 117), and DOAC (n = 182) had comparable baseline characteristics including age (p = 0.25), gender (p = 0.33), and STS-Score (p = 0.072). The proportion of patients having a CHA2DS2-VASc-Score ≥3 (p = 0.791) and HAS-BLED-Score ≥3 (p = 0.185) was not different between groups. The rate of early safety events (with lower values indicating superior safety) was lowest in DOAC (13.2%) and not increased in cVKA (19.7%) compared to iVKA (23.1%) (p = 0.029). Valve Academic Research Consortium-2 defined stroke (p = 0.527) and bleeding (p = 0.097) did not differ between groups. Renal failure occurred more often in iVKA compared to cVKA and DOAC (p = 0.02). All-cause 1-year mortality was 20.1% in iVKA, 13.7% in cVKA, and 8.8% in DOAC (p = 0.015). Multivariate analysis revealed DOAC to be associated with reduced all-cause 1-year mortality (HR 0.56 (95%-CI 0.32 to 0.99), p = 0.047) whereas cVKA was comparable to iVKA (HR 0.75 (95%-CI 0.43 to 1.31), p = 0.307). In conclusion, cVKA did not increase the rate for the composite end point of early safety at 30 days in this cohort of patients. Treatment with a DOAC was associated with a significantly reduced rate of early safety end points at 30 days and lower 1-year mortality.

Background Infective endocarditis ( IE ) after transcatheter aortic valve replacement is a devastating complication associated with a high mortality. Our objective was to determine the impact of cardiac surgery (CS) and antibiotics ( IE ‐ CS ) compared with medical treatment with antibiotics only ( IE ‐ AB x) on 1‐year mortality in patients developing IE after transcatheter aortic valve replacement. Methods and Results Patients developing IE after transcatheter aortic valve replacement were included in this retrospective analysis. All‐cause 1‐year mortality was the primary end point. A total of 20 patients underwent IE ‐ CS compared with 44 patients treated by IE ‐ AB x. In this unmatched cohort, patients treated by IE ‐ AB x were older ( P =0.006), had a higher Society of Thoracic Surgeons score ( P =0.029), and more often had severe chronic kidney disease ( P =0.037). One‐year mortality was not different between groups ( IE ‐CS versus IE‐ABx, 65% versus 68.2%; P =0.802). The rate of any complication during treatment was higher in the IE ‐ CS group ( P =0.024). In a matched cohort, baseline characteristics were not significantly different. All‐cause 1‐year mortality was not different between groups ( IE ‐CS versus IE‐ABx, 65% versus 75%; P =0.490). A Cox regression analysis revealed any indication for surgery (hazard ratio, 6.20; 95% confidence interval, 1.80–21.41; P =0.004), sepsis on admission (hazard ratio, 4.03; 95% confidence interval, 1.97–8.24; P Conclusions In patients developing IE after transcatheter aortic valve replacement, mortality was predicted by the severity of IE and concomitant mitral regurgitation. In this small, and therefore statistically limited, but high‐risk patient cohort, CS provided no significant mortality benefit compared with medical therapy. Individual decision making by a “heart and endocarditis team” is necessary to offer those patients the most reasonable treatment option.

Background Impaired left ventricular (LV) ejection fraction is a common finding in patients with aortic stenosis and serves as a predictor of morbidity and mortality after transcatheter aortic valve replacement. However, conflicting data on the most accurate measure for LV function exist. We wanted to examine the impact of LV ejection fraction, mean pressure gradient, and stroke volume index on the outcome of patients treated by transcatheter aortic valve replacement. Methods and Results Patients treated by transcatheter aortic valve replacement were primarily separated into normal flow ( NF ; stroke volume index >35 mL/m 2 ) and low flow ( LF ; stroke volume index ≤35 mL/m 2 ). Afterwards, patients were divided into 5 groups: “NF–high gradient,” “NF–low gradient” ( NF ‐ LG ), “LF–high gradient,” “paradoxical LF‐LG,” and “classic LF‐LG.” The 3‐year mortality was the primary end point. Of 1600 patients, 789 (49.3%) were diagnosed as having LF , which was characterized by a higher 30‐day ( P =0.041) and 3‐year ( P LF was an independent predictor of all‐cause (hazard ratio, 1.29; 95% confidence interval, 1.03–1.62; P =0.03) and cardiovascular (hazard ratio, 1.37; 95% confidence interval, 1.06–1.77; P =0.016) mortality. Neither mean pressure gradient nor LV ejection fraction was an independent predictor of mortality. Patients with paradoxical LF‐LG (35.0%), classic LF‐LG (35.1%) and LF –high gradient (38.1%) had higher all‐cause mortality at 3 years compared with NF –high gradient (24.8%) and NF ‐ LG (27.9%) ( P =0.001). However, surviving patients showed a similar improvement in symptoms regardless of aortic stenosis entity. Conclusions LF is a common finding within the aortic stenosis population and, in contrast to LV ejection fraction or mean pressure gradient, an independent predictor of all‐cause and cardiovascular mortality. Despite increased long‐term mortality, high procedural success and excellent functional improvement support transcatheter aortic valve replacement in patients with LF severe aortic stenosis.

In primary prevention, regular physical activity decreases the incidence of cardiovascular disease. At the endothelial level, this decreased incidence was attributed to higher expression and phosphorylation of the endothelial isoform of NO synthase, which results in a more effective radical

Background: Summary Left main disease (LMD) and associated cardiac risk factors are often perceived as a limiting factor for the outcome of off-pump coronary artery bypass (OPCAB) grafting. In this study, we assess whether the outcome of OPCAB surgery is affected in such patients. Methods: We retrospectively compared perioperative parameters in 66 OPCAB patients (group A) with LMD and 216 OPCAB patients without (group B) LMD. The patients were operated in the time frame between 2002 and 2007. LMD was defined as a stenosis >50%. Results: Patients in group A had a higher EuroSCORE (logistic: 3.7 ± 0.1 vs 6.3 ± 0.3, p = 0.027), increased coronary artery disease (CAD) family history (p = 0.015) and cerebrovascular accidents (p = 0.027), increased history of congestive heart failure (p = 0.013), more urgent surgery (p = 0.008), previous percutaneous transluminal coronary angioplasties (PTCAs) (p = 0.05) and previous stent implantation (p = 0.023). An intra-aortic balloon pump (IABP) was inserted more frequently in the LMD group preoperatively (p = 0.004). There were two conversions to on-pump during OPCAB surgery. There were no differences in the postoperative outcomes in the LMD group A versus group B, such as cardiac-related events, neurological deficits, cardiac enzyme course, arrhythmias, blood loss, infections and renal failure. Conclusions: The presence of LMD and higher EuroSCORE does not yield adverse outcomes in OPCAB patients

Background— The gut-derived hormone ghrelin, especially its acylated form, plays a major role in the regulation of systemic metabolism and exerts also relevant cardioprotective effects; hence, it has been proposed for the treatment of heart failure (HF). We tested the hypothesis that ghrelin can directly modulate cardiac energy substrate metabolism. Methods and Results— We used chronically instrumented dogs, 8 with pacing-induced HF and 6 normal controls. Human des-acyl ghrelin [1.2 nmol/kg per hour] was infused intravenously for 15 minutes, followed by washout (rebaseline) and infusion of acyl ghrelin at the same dose. 3 H-oleate and 14 C-glucose were coinfused and arterial and coronary sinus blood sampled to measure cardiac free fatty acid and glucose oxidation and lactate uptake. As expected, cardiac substrate metabolism was profoundly altered in HF because baseline oxidation levels of free fatty acids and glucose were, respectively, >70% lower and >160% higher compared with control. Neither des-acyl ghrelin nor acyl ghrelin significantly affected function and metabolism in normal hearts. However, in HF, des-acyl and acyl ghrelin enhanced myocardial oxygen consumption by 10.2±3.5% and 9.9±3.7%, respectively ( P P Conclusions— Acute increases in des-acyl or acyl ghrelin do not interfere with cardiac metabolism in normal dogs, whereas they enhance free fatty acid oxidation and reduce glucose oxidation in HF dogs, thus partially correcting metabolic alterations in HF. This novel mechanism might contribute to the cardioprotective effects of ghrelin in HF.

Background Imatinib mesylate is a selective tyrosine-kinase inhibitor used in the treatment of multiple cancers, most notably chronic myelogenous leukemia (CML). There is evidence that imatinib can induce cardiotoxicity in cancer patients. Our hypothesis is that imatinib alters calcium regulatory mechanisms and can contribute to development of pathological cardiac hypertrophy.

AIM Transcatheter aortic valve implantation has become an alternative to surgery in higher risk patients with symptomatic aortic stenosis. The aim of the ADVANCE study was to evaluate outcomes following implantation of a self-expanding transcatheter aortic valve system in a fully monitored, multi-centre 'real-world' patient population in highly experienced centres. METHODS AND RESULTS Patients with severe aortic stenosis at a higher surgical risk in whom implantation of the CoreValve System was decided by the Heart Team were included. Endpoints were a composite of major adverse cardiovascular and cerebrovascular events (MACCE; all-cause mortality, myocardial infarction, stroke, or reintervention) and mortality at 30 days and 1 year. Endpoint-related events were independently adjudicated based on Valve Academic Research Consortium definitions. A total of 1015 patients [mean logistic EuroSCORE 19.4 ± 12.3% [median (Q1,Q3), 16.0% (10.3, 25.3%)], age 81 ± 6 years] were enrolled. Implantation of the CoreValve System led to a significant improvement in haemodynamics and an increase in the effective aortic valve orifice area. At 30 days, the MACCE rate was 8.0% (95% CI: 6.3-9.7%), all-cause mortality was 4.5% (3.2-5.8%), cardiovascular mortality was 3.4% (2.3-4.6%), and the rate of stroke was 3.0% (2.0-4.1%). The life-threatening or disabling bleeding rate was 4.0% (2.8-6.3%). The 12-month rates of MACCE, all-cause mortality, cardiovascular mortality, and stroke were 21.2% (18.4-24.1%), 17.9% (15.2-20.5%), 11.7% (9.4-14.1%), and 4.5% (2.9-6.1%), respectively. The 12-month rates of all-cause mortality were 11.1, 16.5, and 23.6% among patients with a logistic EuroSCORE ≤10%, EuroSCORE 10-20%, and EuroSCORE >20% (P< 0.05), respectively. CONCLUSION The ADVANCE study demonstrates the safety and effectiveness of the CoreValve System with low mortality and stroke rates in higher risk real-world patients with severe aortic stenosis.

The use of bioprosthetic valves has increased over the last two decades. However, the major drawback is their deterioration and failure over time, requiring redo surgery. Conventional surgical replacement (re-SAVR) has been standard of care, but valve-in-valve deployment of transcatheter aortic

Studies of infective endocarditis (IE) in transcatheter aortic valve replacement patients are limited by univariate analysis of predictors [(1)][1], incomplete patient data (particularly non-IE cases [[2]][2]), or low number of endpoints [(3)][3]. We aimed to investigate the incidence, treatment

Introduction. The existence of human cardiac stem cells (hCSC) and their regenerative capacity are not fully defined. The aim of this study was to identify and analyse the distribution of hCSCs by flow cytometry (FCM). Methods. Tissue samples from the left ventricle (LV) and the appendages of the right atrium (RA) and left atrium (LA) were taken during cardiac surgery. Mononuclear cells (MNCs) were isolated, labelled for the stem-cell-marker c-kit and hematopoietic-lineage markers and analysed by FCM. Results. HCSCs could be isolated from the RA, LA, and LV without significant quantitative difference between both atria (A) (RA 4.80 ± 1.76% versus LA 4.99 ± 1.69% of isolated MNCs, P=0.922). The number of hCSCs was significantly higher in both atria compared to the left ventricle (A 4.90 ± 1.29% versus LV 0.62 ± 0.14% of isolated MNCs, P=0.035). Conclusion. The atria contain a higher concentration of hCSC than the left ventricle. HCSCs located in the atria could serve as an endogenous source for heart regeneration.

The incidence of atrial fibrillation with the need of anticoagulation in patients receiving transcatheter aortic valve replacement (TAVR) is high and it may influence outcome. The aim was to study the impact of pre-existing atrial fibrillation (PEAF) and new-onset atrial fibrillation (NOAF) on

Valve-in-Valve (ViV) for failed surgical aortic valve replacement (SAVR) is an effective treatment for patients that are not able to undergo re-operation. Limited data exist for transcatheter aortic valve replacement (TAVR) as a redo for patients that have undergone TAVR procedures. Baseline

New cerebral embolic lesions (CLs) determined by diffusion-weighted magnetic resonance imaging (DW-MRI) are frequently found in patients treated with transcatheter aortic valve replacement (TAVR). In CLEAN-TAVI trial the number and volume of new CLs were significantly lower using a cerebral

Transcatheter aortic valve replacement (TAVR) has become the standard of care in high-risk patients and patients that are not suitable for surgery. Postdilatation (PD) is mainly performed due to remaining paravalvular aortic regurgitation (AR). However, there are concerns regarding leaflet function

Introduction Exercise is thought to stimulate the release of hematopoietic and endothelial progenitor cells (EPC) from the bone marrow. Little is known about the influence of strenuous exercise on the content of circulating progenitor cells. The aim of this study was to investigate the influence of a marathon race on the amount of circulating progenitor cells immediately after the race in advanced-aged runners. Methods Sixty-eight healthy marathon runners (age: 57 ± 6 years) were included in this study. Blood cell counts were evaluated by standard methods, and circulating progenitor cells before and immediately after the race were quantified by fluorescence-activated cell sorter (FACS). Vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) was quantified by enzyme-linked immunosorbent assay. Results A marathon race led to a significant increase in white blood cell count (5283 ± 155 vs. 13706 ± 373 cells/μl; P < 0.001). Fluorescence-activated cell sorter analysis revealed a significant decrease of CD34pos cells (1829 ± 115 vs. 1175 ± 75 cells/ml blood; P < 0.0001), CD117pos cells (2478 ± 245 vs. 2193 ± 85 cells/ml blood; P < 0.05), and CD133pos cells (3505 ± 286 vs. 2239 ± 163 cells/ml blood; P < 0.001). No significant change was observed for EPCs defined as CD34pos/VEGF-R2pos cells (117 ± 8 vs. 128 ± 9cells/ml blood; P = 0.33). With respect to VEGF a significant downregulation was evident directly after the race (48.9 ± 8.0 vs. 34.0 ± 7.5 pg/ml; P < 0.05), whereas no change was obvious in EGF levels. Conclusion The results of our study suggest that finishing a marathon race will lead to an inflammatory response and downregulation of circulating hematopoietic stem cells. With respect to EPCs no change is observed, which may be because of a greater differentiation of the remaining CD34pos cells towards EPCs.