Post-Market Clinical Follow-Up With the Patent Foramen Ovale Closure Device IrisFIT (Lifetech) in Patients With Stroke, Transient Ischemic Attack, or Other Thromboembolic Events.

BACKGROUND: A patent foramen ovale (PFO) has been associated with embolic strokes and transient ischemic attacks (TIAs). Catheter closure of PFO is effective in preventing recurrent events. Residual shunts and procedure or device related complications can occur, including atrial fibrillation and thrombus formation. This study examines the initial experience with a new PFO closure device, the IrisFIT PFO-Occluder (Lifetech Scientific, Shenzhen, China). METHODS: 95 patients with indications for PFO closure underwent percutaneous closure with the IrisFIT PFO-Occluder. The primary endpoint was the rate of accurate device placement with no/small residual shunt at 3 or 6 months follow-up. All patients underwent transoesophageal echocardiography (TEE) after 1 to 6 months. In case of a residual shunt, an additional TEE was performed after 12 months. Clinical follow-up was performed up to a mean of 33.1 ± 3.6 months. RESULTS: The device was successfully implanted in 95 (100%) patients with no relevant procedural complications. At final TEE follow-up (7.6 ± 3.9 months) the effective closure rate was 96.8% with 1 moderate and 2 large residual shunts. There were 8 cases of new onset atrial fibrillation and 2 TIAs. There were no cases of device embolization or erosion. CONCLUSION: The IrisFIT occluder is a new PFO closure device with several advantages compared to other devices. In this small study cohort, technical success rate, closure rate and adverse event rate were comparable to other devices. The rate of new onset atrial fibrillation was higher in comparison to other studies and warrants further investigation.

Early Multinational Experience of Transcatheter Tricuspid Valve Replacement for Treating Severe Tricuspid Regurgitation.

OBJECTIVES: The aim of this registry was to evaluate the feasibility and safety of transcatheter tricuspid valve implantation (TTVI) in patients with extreme surgical risk. BACKGROUND: Isolated tricuspid regurgitation (TR) surgery is associated with high in-hospital mortality. METHODS: Thirty consecutive patients (mean age 75 ± 10 years; 56% women) from 10 institutions, with symptomatic functional TR, had institutional and notified body approval for compassionate use of the GATE TTVI system. Baseline, discharge, and 30-day follow-up echocardiographic data and procedural, in-hospital, and follow-up clinical outcomes were collected. RESULTS: At baseline, all patients had multiple comorbidities, severe or greater TR, and reduced baseline right ventricular function. Technical success was achieved in 26 of 30 patients (87%). Device malpositioning occurred in 4 patients, with conversion to open heart surgery in 2 (5%). Of those who received the device, 100% had reductions in TR of ≥1, and 75% experienced reductions of ≥2 grades, resulting in 18 of 24 of patients (76%) with mild or less TR at discharge. All patients had mild or less central TR. There was continued improvement in TR grade between discharge and 30 days in 15 of 19 patients (79%). In-hospital mortality was 10%. At mean follow-up of 127 ± 82 days, 4 patients (13%) had died. Of patients alive at follow-up, 62% were in New York Heart Association functional class I or II, with no late device-related adverse events. CONCLUSIONS: Compassionate treatment of severe, symptomatic functional TR using a first-generation TTVI device is associated with significant reduction in TR and improvement in functional status with acceptable in-hospital mortality. Further studies are needed to determine the appropriate patient population and long-term outcomes with TTVI therapy.

Permanent Pacemaker Lead Insertion Connected to an External Pacemaker Generator for Temporary Pacing After Transcatheter Aortic Valve Implantation.

BACKGROUND: Outcomes after transcatheter aortic valve implantation (TAVI) have been demonstrated to be at least equivalent in the short term compared to surgical valve implantation (SAVI). However, Conduction abnormalities are more common after TAVI than SAVI and the need for permanent pacemaker implantation is more common after TAVI with the currently commercially available self-expanding valves than after SAVI. Temporary pacemaker implantation may be associated with inability to ambulate, lead migration or perforation and infection. Depending on the monitoring system, some arrhythmias may not be detected. We examined the feasibility and safety of permanent pacemaker lead implantation connected to an external generator in patients undergoing TAVI at our institution. METHODS: This is a retrospective analysis of consecutive patients (between April 1st 2014 and April 30th 2016) at a single center without permanent pacemaker at the time of TAVI who underwent implantation of a permanent pacemaker lead after TAVI connected to an external generator. Focus was the examination of feasibility and safety of our aforementioned approach. In addition, data analysis was performed separating patients into two groups depending on whether (group 1) or not (group 2) permanent pacemaker implantation was ultimately needed. RESULTS: Per our institutional protocol, all consecutive 114 patients underwent insertion of a permanent pacemaker lead after TAVI connected to an external generator. There was one pericardial effusion on postoperative day one that may have been related to the left ventricular wire for TAVI valve delivery. However, perforation due to the pacemaker lead cannot be excluded. Specifically, no access site complications, lead dislodgments or infections occurred. All patients were able to ambulate after the procedure without delay. The permanent pacemaker lead remained in place on average for 4.3 days in group 1 (n = 10) and 4.4 days in group 2 (n = 104) (variance of 3.8 and 3.4 days respectively, [minimum/maximum 0/11 days and 1 and 12 days]). Of the ten patients (9%) who required permanent pacemaker implantation, 8 had a complete atrioventricular block and two had tachy-brady arrhythmias in the context of atrial fibrillation. None of the baseline characteristics including baseline conduction abnormalities were predictors for PPI. CONCLUSION: Implantation of a permanent pacemaker lead connected to an external generator is feasible and safe and could be a better option than implantation of a temporary lead connected to an external generator. It may allow earlier ambulation and facilitate monitoring.

The IrisFIT Patent Foramen Ovale Closure Device in Patients With History of Cryptogenic Embolization.

BACKGROUND: The aim of this study was to assess safety, efficacy, and clinical outcome of the IrisFIT PFO Closure System (Lifetech Scientific) for transcatheter closure of patent foramen ovale (PFO) in patients with a history of cryptogenic stroke, transient ischemic attack (TIA), or peripheral embolization. PATIENTS AND METHODS: We report the results of 60 consecutive patients undergoing PFO closure with the IrisFIT occluder for secondary prevention of paradoxical embolization. All cases were analyzed for periprocedural and device-related adverse events up to 12 months after implantation. In addition, the patients were evaluated for complete defect closure with transesophageal echocardiography (TEE) after 1 month, 6 months, and (if indicated) 12 months. Mean patient age was 53 ± 14 years and 37 patients (62%) were males. All patients had a history of at least 1 cryptogenic stroke, TIA, or peripheral embolization. RESULTS: Technical success was achieved in all 60 procedures. The mean procedure time was 28 ± 11 minutes. There were no periprocedural or device-related complications up to 12 months after the implant. Successful defect closure at 6 months post device implantation was achieved in 56 cases (93.3%). Within 12 months of follow-up, 2 patients had recurrent TIAs, both with complete PFO sealing at the last TEE prior to the event. CONCLUSION: The IrisFIT PFO Closure System can be used safely and with high technical success for secondary prevention of cryptogenic stroke or peripheral embolization.

Acute Stroke Interventions Performed by Cardiologists: Initial Experience in a Single Center.

OBJECTIVES: The aim of this study was to evaluate the technical and clinical success of acute stroke interventions performed in our interventional cardiology center. BACKGROUND: Dedicated interventional stroke centers remain limited. Interventional cardiologists have established networks of catheterization laboratories and the necessary infrastructure to provide around the clock interventional therapy. These networks may also provide the currently lacking universal rapid access to prompt stroke intervention. METHODS: Between July 2012 and July 2018, 70 consecutive patients underwent acute stroke intervention for large-vessel occlusions. Seventeen patients (24%) had tandem or multiple vessel occlusions. The majority (n = 63, 90%) were admitted via our local stroke unit, and 7 (10%) patients were transferred from other regional referral centers. RESULTS: In 43 (61%) patients, systemic fibrinolytic therapy was started after baseline imaging. Mean time between symptom onset and arrival to the cath lab was 138 min; mean door-to-vascular access time was 64 min; mean time between cath lab activation and its operational readiness was 13 min. In all cases, access to supra-aortic vessels was achieved. Mean time between femoral arterial puncture and lesion crossing was 26 min. Stent implantation for extracranial stenosis or dissection was performed in 14 (20%) cases. Thrombectomy of intracranial occlusions was done with a stent retriever (n = 64, 91%) or an aspiration system (n = 14, 20%). In 20 (28%) cases, a combination of techniques was used. Recanalization was technically successful (Thrombolysis In Cerebral Infarction flow grade 2b or 3) in 65 (93%) patients. The 30-day mortality was 18% (n = 13). Favorable clinical outcome, defined as a modified Rankin Scale score of 0 to 2, was achieved in 61% at 3-month follow-up. CONCLUSIONS: Acute stroke interventions can be performed safely and with high technical and clinical success by experienced interventional cardiologists.

A case of mislabeled textbooks: misnomer of the traditional "bicaval" view.

Since the early beginning of the transesophageal echocardiography (TEE) era, standardized tomographic views describing cardiac key structures have been provided. They have become the basis of TEE and have not been modified for decades. During our recent structural interventional cases, it has come to our attention that the structure frequently labeled "inferior vena cava" in textbooks and journal articles illustrating the bicaval TEE view is, in fact, the coronary sinus. Our manuscript illustrates our observation.

Intraoperative Defibrillation Testing Should Not Be Generally Abandoned for All ICD Procedures-A Multicenter Study on 4,572 Consecutive Patients.

Background The ongoing technical advances in development of new implantable cardioverter defibrillator (ICD) systems led some investigators to question the routine use of intraoperative defibrillation testing (DT). Therefore, we evaluated retrospectively in a multicenter study effectiveness, safety, and usefulness of intraoperative DT on unbiased large patient population. Methods Data from 4,572 consecutive patients undergoing any ICD intervention were retrospectively analyzed. Besides efficacy of DT, risk factors for DT failure were identified in a multiple logistic regression analysis. Results Overall 5,483 shock data from 4,532 patients were available. Not tested for medical reasons were 13.5%. DT-associated complications were not noted. Primary DT effectiveness was 95.8%, whereas 4.2% were ineffective. Optimization (51.6% increase of DT energy, 10.1% subcutaneous lead array (SQ array), 2% generator exchange, 4.8% lead reposition, 9.3% lead exchange, and 22.2% change of shock parameters) led to successful DT in 152 patients (96.2%). Subanalyses and logistic regression identified implantation of generator in any other position than left subpectoral, age, body mass index and left ventricular ejection fraction as independent predictors for primary DT failure. Conclusion The number of patients, including those undergoing generator exchange, system upgrade, or system revision, with inappropriate intraoperative testshock is relatively high. The results of recent prospective clinical trials can be extrapolated only on first ICD implantations with high-energy generators. For patients undergoing subcutaneous ICD implantation, right-sided implantation, patients with channelopathies and hypertrophic cardiomyopathy, as well as for procedures on already implanted ICD systems, the intraoperative DT might still be recommended.

Transcatheter mitral valve repair with the MitraClip(®) can be performed without general anesthesia and without conscious sedation.

BACKGROUND: General anesthesia is known to be associated with an increased risk for complications, especially in elderly and multi-morbid patients, the primary target population of the MitraClip(®) technique. The aim is to assess whether general anesthesia and even conscious sedation can be avoided during the MitraClip(®) procedure. METHODS: A total of 91 consecutive patients who underwent MitraClip(®) implantation [median 77 years, (IQR 72-83), 40 % female] were retrospectively analyzed. The first 26 patients were treated in general anesthesia. Afterwards, local anesthesia was chosen as primary anesthetic approach. Altogether, 28 (31 %) patients received general anesthesia, local anesthesia was performed in 35 (38 %) patients with sedation and in 28 (31 %) patients without sedation. RESULTS: The respective patient groups were similar regarding their baseline characteristics. Procedural success (successful implantation of at least one clip and post-procedure MR grade ≤2) was achieved in 89 % with no difference between the groups (93 % in general anesthesia, 89 % in local anesthesia with sedation, 86 % in local anesthesia without sedation, p = ns). No difference regarding hospital complications was noted. Local anesthesia with and without sedation was associated with less necessity for ICU/IMC stay (100 % in general anesthesia, 14 % in local anesthesia with sedation, 14 % in local anesthesia without sedation; p < 0.0001). One-year estimated survival was not significantly different among the groups (63, 82 and 75 %; p = ns). CONCLUSIONS: Transcatheter mitral valve repair with the MitraClip(®) can be performed without general anesthesia and even without conscious sedation with similar procedural success and complication rates.

True First-Line Local-Anesthesia Only Protocol for Transfemoral TAVI.

AIMS: To evaluate the safety and feasibility of transcatheter aortic valve implantation (TAVI) via femoral access under local anesthesia only (without concomitant sedation) as the initial strategy. METHODS AND RESULTS: Patients undergoing planned transfemoral TAVI without routine general anesthesia between May 2005 and December 2013 were identified. Baseline characteristics, procedural outcomes, and a 30-day clinical follow-up were obtained. A total of 215 patients underwent TAVI with local anesthesia only as the initial strategy (LA group). Of these patients, 40 (18.6%) received additional sedation (LAS group) during the procedure due to inadequate pain control or agitation and 7 patients (3.3%) underwent conversion to general anesthesia (GA group). TAVI was successfully performed in 211 cases (98.2%). When 30-day outcomes for patients requiring only local anesthesia were compared with patients requiring additional sedation, there was a significantly longer duration of Intensive Care Unit (ICU) stay in the group with additional sedation (LAS, 5.0 days [range, 3.0-6.0 days] vs LA 3 days [range, 2.0-5.0 days]; P=.02) and general anesthesia (GA 7.0 days [range, 2.5-18.0 days] vs LA 3 days [range, 2.0-5.0]; P=.04). CONCLUSION: Our study suggests that TAVI with LA only as the initial strategy is a feasible alternative to GA, with potential benefit of this strategy over using routine concomitant sedation. LA only may be considered a primary option in many patients.

"A bend in time": Shaping the sheath facilitates left atrial appendage closure.

OBJECTIVES: The purpose of this study is to determine feasibility, safety, and effectiveness of the "shape-the-sheath" method in left atrial appendage closure. BACKGROUND: LAA occlusion is often a difficult procedure, due to not just the learning curve but also the three-dimensional variable nature of the left atrial appendage. Multiple sheaths have been created for various takeoffs. The purpose of this article is to show the feasibility of the "shape-the-sheath" method in left atrial appendage closure. METHODS: Ten consecutive patients undergoing LAA occlusion without the "shape-the-sheath" method were compared to 10 consecutive patients undergoing LAA occlusion with the "shape-the-sheath" method using the Amplatzer Cardiac Plug (ACP) system and the Amplatzer TorqVue 45×45 sheath. RESULTS: The "shape-the-sheath" method resulted in significant decreases in fluoroscopy time (7.2±3.0 min vs. 13.7±6.7 min, P<0.05), number of partial recaptures (0% vs. 50%, P<0.05), with a trend toward decrease in the number of complete recaptures (0 vs. 40%, P=0.09) compared to conventional sheath use. CONCLUSIONS: Shaping-the-sheath is a simple, elegant way to help conform delivery systems to better access the LAA and ensure stable position. Further experience with this procedure optimization step is warranted.

Devices in heart failure--the new revolution.

Heart failure is a growing epidemic, with more patients living longer and suffering from this disease. There is a growing segment of patients who have persistent symptoms despite pharmacologic therapy. In an era when transplants are rare, the need for devices and interventions that can assist ventricular function is paramount. This review goes through the devices used in heart failure, including left ventricular reconstruction, aortic counterpulsation, short-term mechanical circulatory support, long-term mechanical circulatory support, and right heart interventions.

Use of EchoNavigator, a novel echocardiography-fluoroscopy overlay system, for transseptal puncture and left atrial appendage occlusion.

Structural heart disease requires a coordinated effort to join echocardiographic and fluoroscopic data. Various methods have been used, including echocardiography, CT, and MRI. We report on the use of EchoNavigator (Philips Inc., Amsterdam, Netherlands), a novel echocardiographic-fluoroscopic fusion system. This new system allows real-time integration and marking of important structures that track on fluoroscopy even with movement of the C-arm. In this article, we describe potential uses for this system in respect to transseptal puncture and left atrial appendage closure.

Staurosporine and extracellular matrix proteins mediate the conversion of small cell lung carcinoma cells into a neuron-like phenotype.

Small cell lung carcinomas (SCLCs) represent highly aggressive tumors with an overall five-year survival rate in the range of 5 to 10%. Here, we show that four out of five SCLC cell lines reversibly develop a neuron-like phenotype on extracellular matrix constituents such as fibronectin, laminin or thrombospondin upon staurosporine treatment in an RGD/integrin-mediated manner. Neurite-like processes extend rapidly with an average speed of 10 µm per hour. Depending on the cell line, staurosporine treatment affects either cell cycle arrest in G2/M phase or induction of polyploidy. Neuron-like conversion, although not accompanied by alterations in the expression pattern of a panel of neuroendocrine genes, leads to changes in protein expression as determined by two-dimensional gel electrophoresis. It is likely that SCLC cells already harbour the complete molecular repertoire to convert into a neuron-like phenotype. More extensive studies are needed to evaluate whether the conversion potential of SCLC cells is suitable for therapeutic interventions.

Antimicrobial responses of primary gingival cells to Porphyromonas gingivalis.

BACKGROUND: Human beta-defensins (hBDs) and the C-C chemokine ligand 20 (CCL20) produced by gingival epithelial cells (GECs) and fibroblasts (HGFs) are antimicrobial peptides (AMPs) that play an important role in innate immunity. The aim of this study was to determine the differential immune response of GECs and HGFs to the oral commensal Streptococcus gordonii (SG) and the pathogen Porphyromonas gingivalis (PG). MATERIAL AND METHODS: In addition to the analysis of gingival biopsies, primary GECs and HGFs were exposed to SG and/or PG, and expression of various AMPs and pro-inflammatory mediators was studied by real-time PCR and ELISA. RESULTS: Gene expression of AMPs was detected in gingival connective tissue. Both SG and PG induced the mRNA-expression of hBD-2 and hBD-3 in GECs as well as HGFs after 24 h (p < 0.05). In HGFs, the commensal bacterium SG stimulated the mRNAs of hBD-3 and CCL20 after 24 h (p < 0.05), while not in GECs. In GECs, the inductive effect of PG on the mRNA-expression of hBD-2 was amplified when cells were first exposed to commensal SG (for 1 h) prior to stimulation with PG (SG-PG; p < 0.05). CONCLUSION: Our data indicate that cell-bacteria interactions and/or bacteria-bacteria cross-talk may have an impact on AMP-regulation in gingiva.

Skin tumor formation in human papillomavirus 8 transgenic mice is associated with a deregulation of oncogenic miRNAs and their tumor suppressive targets.

BACKGROUND: Dysregulation of microRNA (miRNA) expression is regularly found in various types of cancer and contributes to tumorigenic processes. However, little is known about miRNA expression in non-melanoma skin cancer in which a pathogenic role of beta human papillomaviruses (HPV) is discussed. A carcinogenic potential of beta HPV8 could be demonstrated in a transgenic mouse model, expressing all early genes of HPV8 (HPV8-CER). A single UVA/B-dose induced oncogene expression and led to papilloma growth within three weeks. OBJECTIVE: Expression of miRNAs and their targets during HPV8-mediated tumor formation in mice. METHODS: Skin of untreated or UV-irradiated wild-type and HPV8-CER mice was analyzed for miRNA expression and localization by qPCR and in situ hybridization. MiRNA target protein expression was analyzed by immunohistochemical staining. RESULTS: Early steps in skin tumor formation in HPV8-CER mice were associated with an upregulation of the oncogenic miRNA-17-5p, -21 and -106a and a downregulation of the tumor-suppressive miRNA-155 and -206, which could be demonstrated by qPCR and in situ hybridization. The respective targets of miRNA-21 and -106a, the tumor suppressors PTEN, PDCD4 and Rb with their pivotal role in cell cycle regulation, apoptosis and proliferation were found to be downregulated. CONCLUSION: This is the first report demonstrating that a cutaneous HPV type deregulates the expression of miRNAs. These deregulations are closely related to the UV-induced upregulation of HPV8 oncogene levels, which suggest a direct or indirect HPV8-specific effect on miRNA expression. These data presume that HPV8 interferes with the miRNA mediated gene regulation to induce tumorigenesis.

CDKN2BAS is associated with periodontitis in different European populations and is activated by bacterial infection.

Epidemiological studies have indicated a relationship between coronary heart disease (CHD) and periodontitis. Recently, CDKN2BAS was reported as a shared genetic risk factor of CHD and aggressive periodontitis (AgP), but the causative variant has remained unknown. To identify and validate risk variants in different European populations, we first explored 150 kb of the genetic region of CDKN2BAS including the adjacent genes CDKN2A and CDKN2B, covering 51 tagging single nucleotide polymorphisms (tagSNPs) in AgP and chronic periodontitis (CP) in individuals of Dutch origin (n=313). In a second step, we tested the significant SNP associations in an independent AgP and CP population of German origin (n=1264). For the tagSNPs rs1360590, rs3217992, and rs518394, we could validate the associations with AgP before and after adjustment for the covariates smoking, gender and diabetes, with SNP rs3217992 being the most significant (OR 1.48, 95% CI 1.19 to 1.85; p=0.0004). We further showed in vivo gene expression of CDKN2BAS, CDKN2A, CDKN2B, and CDK4 in healthy and inflamed gingival epithelium (GE) and connective tissue (CT), and detected a significantly higher expression of CDKN2BAS in healthy CT compared to GE (p=0.004). After 24 h of stimulation with Porphyromonas gingivalis in Streptococcus gordonii pre-treated gingival fibroblast (HGF) and cultured gingival epithelial cells (GECs), we observed a 25-fold and fourfold increase of CDKN2BAS gene expression in HGFs (p=0.003) and GECs (p=0.004), respectively. Considering the global importance of CDKN2BAS in the disease risk of CHD, this observation supports the theory of inflammatory components in the disease physiology of CHD.

Phl p 5 resorption in human oral mucosa leads to dose-dependent and time-dependent allergen binding by oral mucosal Langerhans cells, attenuates their maturation, and enhances their migratory and TGF-beta1 and IL-10-producing properties.

BACKGROUND: Sublingual immunotherapy (SLIT) is safe and effective as treatment of allergic rhinitis and mild asthma. Oral mucosal Langerhans cells (oLCs) play a central role. However, little is known about allergen binding by oLCs during mucosal allergen resorption and its impact on oLC functions. OBJECTIVE: Binding of Phl p 5 to oLCs was studied in a standardized ex vivo model to investigate mechanisms important for SLIT. METHODS: Human oral mucosal biopsies were incubated with the grass pollen allergen Phl p 5. Migration, binding of Phl p 5, phenotype and cytokine production, and T-cell priming of Phl p 5-binding oLCs were analyzed. RESULTS: Significant uptake required more than 5 minutes, and dose-dependent binding of Phl p 5 to oLCs was saturated at 100 microg/mL Phl p 5. Furthermore, Phl p 5 significantly increased the migratory capacity of oLCs but attenuated their maturation and strongly promoted the release of TGF-beta1 and IL-10 by oLCs themselves as well as by cocultured T cells. CONCLUSION: Oral mucosal Langerhans cells bind Phlp5 in a dose-dependent and time-dependent manner, leading to an increased production of tolerogenic cytokines and an enhanced migratory capacity but decelerated maturation of oLCs.