Interventional occlusion of left atrial appendage in patients with atrial fibrillation. Gender-related outcomes in the German LAARGE Registry.

INTRODUCTION: Gender-based differences in atrial fibrillation have been identified, but limited data exist for patients undergoing left atrial appendage occluder (LAAO) implantation. This study reports gender-related periprocedural and 1-year outcomes of the prospective, multicenter German left atrial appendage occlusion registry (LAARGE). METHODS: LAARGE enrolled 641 patients who were scheduled for LAAO implantation from July 2014 to January 2016 in 38 hospitals in Germany. The data collected included demographics, clinical characteristics, details of implantation, and outcome. Efficacy and safety at 1-year follow-up were assessed by the occurrence of thrombembolic and bleeding events, as well as mortality. RESULTS: Of 638 patients undergoing LAAO implantation 38.9% were female and 61.1% male. Females were older (76.4 ± 8.2 [females] vs. 75.6 ± 7.7 [males], p = .042) and had a higher stroke risk (CHA2 DS2 -VASc score: 4.9 ± 1.5 vs. 4.3 ± 1.5, p < .001). In contrast, males suffered more often from coronary artery (33.1% vs. 53.8%, p < .001) and vascular disease (18.5% vs. 31.0%, p < .001). Technical success was high and similar for both genders (98.4% vs. 97.2%, p = .33). Severe periprocedural complications (6.9% vs. 3.1%, p = .032) occurred more often in females. At 1-year follow-up the rates of all-cause stroke (0.5% vs. 1.3%, p = .65) and severe bleeding (0.0% and 1.0%, p = .29) were low and comparable between the genders. Also, one-year all-cause mortality (9.2% vs. 13.1%, p = .14) did not differ significantly. CONCLUSION: LAARGE documented in this elderly patient population undergoing LAAO implantation a higher rate of severe periprocedural complications in females. At 1-year follow-up similar efficacy and safety outcomes were observed for both genders.

Initial experience with percutaneous mitral valve repair in patients with cardiac amyloidosis.

BACKGROUND: Percutaneous mitral valve repair (PMVR) is a therapeutic option for severe mitral regurgitation (MR) in patients with heart failure due to differential aetiologies. However, only little is known about the safety and efficacy of this procedure in patients with amyloid cardiomyopathy. METHODS: Five patients with cardiac amyloidosis and moderate to severe or severe MR undergoing PMVR were analysed retrospectively and compared to seven patients with cardiac amyloidosis and severe MR without intervention. Clinical and functional data, renal function and cardiac biomarkers as well as established risk scores for cardiac amyloidosis were assessed. Primary endpoint was the reduction in MR one year after PMVR. Secondary endpoints were safety, overall mortality after 12 months compared with the control group, as well as changes in clinical and functional parameters. RESULTS: Amyloidosis risk assessment documented amyloid cardiomyopathy at an advanced stage in all patients. Procedural, technical and device success of PMVR were all 100% and residual MR remained mild to moderate at 12 months follow-up (P = .038 vs before PMVR). Differences in survival compared with the control (no PMVR) group pointed to a possible survival benefit in the PMVR group (P = .02). CONCLUSION: PMVR is a feasible and safe procedure in patients with cardiac amyloidosis and might carry a possible survival benefit in this patient group.

Percutaneous mitral valve repair in recurrent severe mitral valve regurgitation after mitral annuloplasty : MitraClip-in-the-ring as a complementary strategy.

BACKGROUND: Patients with reduced left ventricular (LV) function undergoing coronary artery bypass graft surgery or/and aortic valve replacement occasionally show severe mitral valve (MV) regurgitation and thus also undergo surgical mitral annuloplasty. Over time, further deterioration of LV function and additional ischemic events cause recurrence of severe MV regurgitation due to the Carpentier IIIb morphology of the MV that is not adequately addressed by the previously implanted annuloplasty ring. METHODS: Seven patients (Society of Thoracic Surgeons score: 7.5 ± 1.5%) with Carpentier type-IIIb recurrent severe MV regurgitation, having undergone prior cardiothoracic surgery (median: 40 months) including mitral annuloplasty, were treated with the MitraClip device. RESULTS: MitraClip implantation resulted in significantly reduced MV regurgitation and improved New York Heart Association functional state, translating into an increased exercise capability and improved cardiac biomarkers. The morphology of the MV was adequately addressed without causing relevant MV stenosis, while the MV annulus area remained unaltered. The procedure was safe with a 30-day mortality rate of 0%. CONCLUSION: MitraClip-in-the-ring is feasible and in principle safe for treating Carpentier type IIIb severe MV regurgitation after surgical MV repair using mitral annuloplasty. MitraClip-in-the-ring resulted in immediate amelioration of clinical symptoms and increased physical exercise capacity.

Identification of patients at higher risk for myocardial injury following elective coronary artery intervention.

OBJECTIVES: To evaluate myocardial injury and infarction (MI) following elective percutaneous coronary intervention (PCI). BACKGROUND: The substantially higher analytical power of high-sensitivity troponin (hsTn) assays allows detection of minor cardiac troponin (cTn) levels, which may be useful in monitoring myocardial injury and guiding therapies. METHODS: Serial hsTnT measurements were conducted in patients undergoing elective PCI and were related to the extent of coronary artery disease (CAD) as reflected by the SYNTAX score risk categories and American College of Cardiology/American Heart Association classification of coronary lesions. Myocardial injury and MI were diagnosed according to the second and third versions of universal MI definition. RESULTS: The study population consisted of 530 patients, who were grouped into low (41.3%), intermediate (35.4%), and high (23.3%) SYNTAX risk categories. The treated coronary lesions were classified into A 7.8%, B1 24.1%, B2 21.1%, C1 24.6%, and C2 22.4%. Postprocedural hsTnT increases correlated significantly with the complexity of treated coronary lesions (p < .05) and CAD magnitude (p < .05). Rates of MI type 4a according to the second and third MI definition criteria were 98 (27.5%) and 15 (4.2%) cases in patients with normal baseline hsTnT values (N = 357, 67.4%), as well as 137 (79.2%) and 27 (15.6%) cases in those with elevated baseline hsTnT values (N = 173, 32.6%), respectively. CONCLUSIONS: After elective PCI, cTn releases correlate significantly with lesion complexity and CAD extent. Use of hsTnT assay enables precise monitoring of PCI-related myocardial injury and may identify patients at higher risk for ischemic events, who may benefit from potent platelet inhibition, which needs to be investigated in randomized trials.

Percutaneous repair of severe mitral valve regurgitation secondary to chordae rupture in octogenarians using MitraClip.

OBJECTIVES: The aim of this study was to assess feasibility and clinical effectiveness of the MitraClip device in octogenarians suffering from severe mitral valve regurgitation due to chordae rupture. BACKGROUND: The MitraClip procedure is a suitable technique in high-risk surgical patients to achieve safe and effective percutaneous repair of mitral valve regurgitation. Octogenarians show cumulative risk and social aspects hindering mitral valve surgery. No data exists regarding the use of the MitraClip device in high-risk octogenarians suffering from mitral valve chordae rupture. METHODS: Between October 2009 and March 2017 98 high-risk octogenarians (society of thoracic surgeons score [STS]: 9.7% ± 0.8) with mitral valve prolapse and consecutively chordae rupture were treated with the MitraClip after interdisciplinary discussion. RESULTS: Successful mitral valve repair was achieved in 91% of the octogenarians. Repair of the mitral valve caused immediate and significant reduction of dyspnoea (NYHA class: 3.5 ± 0.4 vs 2.0 ± 0.3; P < 0.001), cardiac reverse remodeling (LVESD: 39 ± 0.8 vs 35 ± 0.8; P < 0.01) and amelioration of cardiac biomarkers (NTproBNP (4884 ± 52 ng/L vs 2473 ± 210 ng/L; P < 0.05,). Effects were stable over the 12 months observation period. None of our patients died intraprocedurally. CONCLUSIONS: Percutaneous repair of chordae rupture is feasible and safe in high-risk octogenarians. The MitraClip should be considered to repair severe mitral valve regurgitation due to mitral valve chordae rupture in high-risk octogenarians after interdisciplinary discussion even facing a challenging anatomy.

Percutaneous repair of mitral valve regurgitation in patients with severe heart failure: comparison with optimal medical treatment.

BACKGROUND: Occurrence of severe mitral valve (MV) regurgitation (MR) is an independent negative predictor of mortality in patients with severe systolic heart failure (HF). This study examines clinical effects and cardiac reverse remodelling in patients with severe systolic HF receiving percutaneous mitral valve repair (PMVR) using MitraClip in comparison to patients receiving optimal medical therapy only. METHODS: Between 2010 and 2014, 86 patients (Society of Thoracic Surgeons score: 10.5% ± 1.2%) with severe HF (left ventricular [LV] ejection fraction; LVEF: 25% ± 2%; LV endsystolic diameter [LVESD]: 55 ± 3 mm) and severe MR received PMVR using MitraClip. Cardiac reverse remodelling and clinical parameters were compared to HF patients with severe MR (from our HF outpatient clinic; n = 69; LVEF: 26% ± 1.4%; LVESD: 53 ± 2 mm) receiving optimal medical therapy (OMT) only. All patients received stable OMT and were characterised by echocardiography, 6-minwalk-distance test and cardiac biomarkers within a 24 months observation period. RESULTS: PMVR in patients with end-stage HF and severe MR resulted in reduction of MR and significant additional cardiac reverse remodelling (LVEF: 26 ± 1.4 vs. 33% ± 2%, p < .05; LVESD: 53 ± 2 vs. 47 ± 2 mm, p < .05) over the 24 months observation period as compared to pharmacologically-only managed comparators. CONCLUSIONS: Both OMT and PMVR cause cardiac reverse remodelling and relief of symptoms in patients with HF and severe MR. PMVR results in significant additional cardiac reverse remodelling compared to pharmacologically-only managed patients.

Short and long-term results after endovascular management of vascular complications during transfemoral aortic valve implantation.

Background Vascular injury and access site complications in the contemporary setting of transcatheter aortic valve implantation (TAVI) are known to be associated with increased mortality and morbidity. The aim of our study was to analyse the feasibility and safety of percutaneous treatment of such vascular complications using a stent graft. Methods Between January 2010 and April 2013, 36 TAVI patients developed severe access site complications and underwent subsequent interventional treatment with a covered stent. Acute treatment success was confirmed by angiography immediately after the implantation of the stent graft, with clinical long-term patency follow-up being assessed by duplex ultrasound. Results Of the 36 patients evaluated, percutaneous treatment of the acute access site bleeding was successful in 35 patients (97%), with one patient requiring surgical intervention due to insufficient haemostasis after stent graft implantation. A subset of 5 patients underwent successful ipsilateral stent graft implantation, either because crossover sheath placement was not feasible (n = 1), or intentionally with an even sheathless approach in an effort to reduce vessel injury (n = 4). After a mean follow-up of 22 ± 8 months, stent graft patency was confirmed by duplex ultrasound in 13 patients with an additional 5 patients reporting to be free from symptoms and claudication. Thirteen patients died within the first 24 months after the procedure, however, none was due to access vessel complications. Five patients were lost for follow-up. Conclusions Our data confirm that endovascular treatment of access site complications related to TAVI is feasible, safe and efficacious, resulting in long-term vascular patency.

The Effects of Mitral Valve Repair on Memory Performance, Executive Function, and Psychological Measures in Patients With Heart Failure.

OBJECTIVES: Heart failure (HF) is a prevalent disease that remains costly and associated with a high mortality rate. HF is also associated with poor neurocognitive functioning. For the treatment for HF patients with severe mitral regurgitation, the MitraClip device has emerged as a promising interventional tool that reduces the mitral valve leakage and thus increases cardiac output. Currently, there is only limited knowledge on changes in cognitive and psychosocial functioning before and after the MitraClip intervention. METHODS: Cognitive function (memory and executive function) and psychosocial measures (depression, anxiety, and quality of life) were assessed before and after the MitraClip intervention in 24 HF patients and 23 healthy participants (comparison group). RESULTS: MitraClip intervention in HF patients was followed by improvements in figural long-term memory (p = .003) and executive function (planning ability, p < .001) relative to the comparison group. In addition, the intervention resulted in a significant improvement in depression (p = .002), anxiety (p = .003) and quality of life scores (physical p = .017, mental p = .013) as well as improved 6-minute walk test results over time (p = .002). CONCLUSIONS: The presented data provide evidence of a significant improvement in memory and executive function as well as in depression, anxiety, and quality of life scores in patients with chronic HF after MitraClip intervention. Further research is needed to shed light on the long-term development of cognitive function, psychosocial well-being, and clinical parameters after MitraClip intervention and how these factors depend on one another.

S100A1 DNA-based Inotropic Therapy Protects Against Proarrhythmogenic Ryanodine Receptor 2 Dysfunction.

Restoring expression levels of the EF-hand calcium (Ca(2+)) sensor protein S100A1 has emerged as a key factor in reconstituting normal Ca(2+) handling in failing myocardium. Improved sarcoplasmic reticulum (SR) function with enhanced Ca(2+) resequestration appears critical for S100A1's cyclic adenosine monophosphate-independent inotropic effects but raises concerns about potential diastolic SR Ca(2+) leakage that might trigger fatal arrhythmias. This study shows for the first time a diminished interaction between S100A1 and ryanodine receptors (RyR2s) in experimental HF. Restoring this link in failing cardiomyocytes, engineered heart tissue and mouse hearts, respectively, by means of adenoviral and adeno-associated viral S100A1 cDNA delivery normalizes diastolic RyR2 function and protects against Ca(2+)- and ß-adrenergic receptor-triggered proarrhythmogenic SR Ca(2+) leakage in vitro and in vivo. S100A1 inhibits diastolic SR Ca(2+) leakage despite aberrant RyR2 phosphorylation via protein kinase A and calmodulin-dependent kinase II and stoichiometry with accessory modulators such as calmodulin, FKBP12.6 or sorcin. Our findings demonstrate that S100A1 is a regulator of diastolic RyR2 activity and beneficially modulates diastolic RyR2 dysfunction. S100A1 interaction with the RyR2 is sufficient to protect against basal and catecholamine-triggered arrhythmic SR Ca(2+) leak in HF, combining antiarrhythmic potency with chronic inotropic actions.

Heart failure gene therapy: the path to clinical practice.

Gene therapy, aimed at the correction of key pathologies being out of reach for conventional drugs, bears the potential to alter the treatment of cardiovascular diseases radically and thereby of heart failure. Heart failure gene therapy refers to a therapeutic system of targeted drug delivery to the heart that uses formulations of DNA and RNA, whose products determine the therapeutic classification through their biological actions. Among resident cardiac cells, cardiomyocytes have been the therapeutic target of numerous attempts to regenerate systolic and diastolic performance, to reverse remodeling and restore electric stability and metabolism. Although the concept to intervene directly within the genetic and molecular foundation of cardiac cells is simple and elegant, the path to clinical reality has been arduous because of the challenge on delivery technologies and vectors, expression regulation, and complex mechanisms of action of therapeutic gene products. Nonetheless, since the first demonstration of in vivo gene transfer into myocardium, there have been a series of advancements that have driven the evolution of heart failure gene therapy from an experimental tool to the threshold of becoming a viable clinical option. The objective of this review is to discuss the current state of the art in the field and point out inevitable innovations on which the future evolution of heart failure gene therapy into an effective and safe clinical treatment relies.

S100A1 deficiency impairs postischemic angiogenesis via compromised proangiogenic endothelial cell function and nitric oxide synthase regulation.

RATIONALE: Mice lacking the EF-hand Ca2+ sensor S100A1 display endothelial dysfunction because of distorted Ca2+ -activated nitric oxide (NO) generation. OBJECTIVE: To determine the pathophysiological role of S100A1 in endothelial cell (EC) function in experimental ischemic revascularization. METHODS AND RESULTS: Patients with chronic critical limb ischemia showed almost complete loss of S100A1 expression in hypoxic tissue. Ensuing studies in S100A1 knockout (SKO) mice subjected to femoral artery resection unveiled insufficient perfusion recovery and high rates of autoamputation. Defective in vivo angiogenesis prompted cellular studies in SKO ECs and human ECs, with small interfering RNA-mediated S100A1 knockdown demonstrating impaired in vitro and in vivo proangiogenic properties (proliferation, migration, tube formation) and attenuated vascular endothelial growth factor (VEGF)-stimulated and hypoxia-stimulated endothelial NO synthase (eNOS) activity. Mechanistically, S100A1 deficiency compromised eNOS activity in ECs by interrupted stimulatory S100A1/eNOS interaction and protein kinase C hyperactivation that resulted in inhibitory eNOS phosphorylation and enhanced VEGF receptor-2 degradation with attenuated VEGF signaling. Ischemic SKO tissue recapitulated the same molecular abnormalities with insufficient in vivo NO generation. Unresolved ischemia entailed excessive VEGF accumulation in SKO mice with aggravated VEGF receptor-2 degradation and blunted in vivo signaling through the proangiogenic phosphoinositide-3-kinase/Akt/eNOS cascade. The NO supplementation strategies rescued defective angiogenesis and salvaged limbs in SKO mice after femoral artery resection. CONCLUSIONS: Our study shows for the first time downregulation of S100A1 expression in patients with critical limb ischemia and identifies S100A1 as critical for EC function in postnatal ischemic angiogenesis. These findings link its pathological plasticity in critical limb ischemia to impaired neovascularization, prompting further studies to probe the microvascular therapeutic potential of S100A1.

Using the GORE® Septal Occluder (GSO) in challenging patent foramen ovale (PFO) anatomies.

OBJECTIVES: We assessed efficacy and safety of the Gore(®) Septal Occluder (GSO) for patent foramen ovale (PFO) closure focusing on patients with challenging septal anatomies. BACKGROUND: In times of controversial discussion whether percutaneous PFO closure is superior to medical therapy for the prevention of recurrent embolic events after cryptogenic stroke, patient selection should mainly focus on individuals with an increased likelihood that the ischaemic event is related to the PFO. In this context, specific septal anatomies-such as the presence of an atrial septal aneurysm as well as long PFO tunnel anatomy-have been associated with a higher rate of cerebrovascular accidents. METHODS: The GSO was used for PFO closure in 41 patients presenting with either atrial septal aneurysm (ASA; 27/41; 65.9%) or long PFO tunnel (> 10 mm; 32/41; 78%). Seven of these patients even presented with a tunnel length ≥ 20 mm (7/41; 17.1%). Eighteen patients had both, long-tunnel anatomy and ASA (18/41; 43.9%). RESULTS: The GSO was successfully implanted in all cases. No procedural complications occurred and all patients were discharged the day after the procedure. Short-term follow-up, including TEE examination, in all patients was performed 37.6 ± 9.0 days after the procedure. Mid-term follow-up was performed after 192.7 ± 45.3 days. Later complications occurred in 7.3% (2 new onset atrial fibrillation, 1 device thrombus). Only 3 patients (7.3%) had more than trace residual shunts at 6-weeks follow-up. At 6-months follow-up, the complete closure rate was 95.1% (39/41). CONCLUSIONS: The Gore(®) Septal Occluder is an efficient device for patent foramen ovale closure in challenging anatomies, including long-tunnel PFOs and atrial septal aneurysms.

First experience with the new generation Edwards Sapien 3 aortic bioprosthesis: procedural results and short term outcome.

BACKGROUND: TAVR has become an established treatment for severe symptomatic aortic stenosis in patients with high surgical risk. The latest generation of the balloon-expandable Edwards Sapien device, the Sapien 3, together with its new transfemoral Commander delivery system has been designed to reduce paravalvular regurgitation and vascular access site complications. OBJECTIVES: To evaluate procedural results and short term outcome with the third generation Sapien 3 device. METHODS: We retrospectively evaluated 125 consecutive TAVR patients and analyzed the first 51 patients in whom we implanted the new Sapien 3 device via transfemoral access. RESULTS: In patients implanted with the Sapien 3 device significant residual paravalvular regurgitation after TAVR was virtually absent with the vast majority having none or trace postinterventional aortic regurgitation on angiography or echocardiography (92.2% and 80.4% respectively). None of the patients had more than mild paravalvular regurgitation. Major vascular access site complications or major bleeding according to the VARC II criteria were not observed in our cohort, minor vascular complications and minor bleeding occurred in 7.8% and 5.9% respectively. If vascular complications occurred, they were related to closure device failure. Thirty day outcome showed a 1.9% major stroke rate and 3.9% death rate. However, we observed a 25.5% permanent pacemaker rate in our Sapien 3 cohort. CONCLUSIONS: Implantation of the new third generation Sapien 3 device resulted in excellent procedural and short term outcome. Significant paravalvular regurgitation was virtually absent. However, the increased rate of postinterventional pacemaker implantations needs to be analyzed in a larger cohort of patients.

Procedural results with the self-expanding 31 mm CoreValve aortic bioprosthesis in patients with large annuli.

BACKGROUND: Transcatheter aortic valve implantation has become an established treatment for severe aortic stenosis in patients with high surgical risk. Due to its specific design, the self-expanding 31 mm CoreValve prosthesis can be technically challenging. This is especially true for patients with large annuli above 27.5 mm for which the CoreValve 31 mm device is the only option. OBJECTIVES: To evaluate procedural results and short-term outcome with the 31 mm CoreValve device in patients with large annuli. METHODS: We retrospectively analyzed 54 patients in whom we implanted a 31 mm self-expanding CoreValve bioprosthesis and compared them to 50 consecutive patients implanted with the smaller 29 mm device within the same period of time. RESULTS: Patients with the 31 mm prosthesis had significantly higher rates of postinterventional pacemaker implantations (35% vs. 20%; P = 0.036) despite similar implantation depths (6.5 ± 4 vs. 7.5 ± 4; P = 0.34). However, the number of deep implantations (>8 mm) was significantly higher (P = 0.045). No significant difference could be observed with respect to cases with ≥Grade 2 postinterventional aortic regurgitation (8% vs. 12.9%; P = 0.5294). Major vascular complications (4% vs. 3.7%; P = ns), 30-day mortality (8% vs. 7.7%; P = ns), and major stroke (3.8% vs. 2%; P = ns) were not different between the 2 groups. CONCLUSION: Despite the technical challenges, procedural results with the 31 mm self-expanding CoreValve prosthesis in large anatomies were similar to those with the smaller sized 29 mm version of the device. However, postinterventional pacemaker rates were significantly higher in the 31 mm cohort despite comparable implantation depths, which might be the result of the specific design of the device.

AAV6.ßARKct cardiac gene therapy ameliorates cardiac function and normalizes the catecholaminergic axis in a clinically relevant large animal heart failure model.

AIMS: G protein-coupled receptor kinase 2 (GRK2), which is markedly upregulated in failing human myocardium, has been implicated as a contributing factor or consequence of heart failure (HF). Importantly, cardiac-specific GRK2 knockout mice have recently proved the pathological nature of GRK2 in HF. Targeted inhibition of GRK2 is possible using a peptide inhibitor known as the ßARKct, which has rescued several disparate small animal HF models. This study was designed to evaluate long-term ßARKct expression in a clinically relevant large animal HF model, using stable myocardial gene delivery with adeno-associated virus serotype 6 (AAV6). METHODS AND RESULTS: A porcine model of HF subsequent to left ventricular (LV) myocardial infarction (MI) was used to study the effects of retrograde injection into the anterior interventricular vein of either AAV6.ßARKct or AAV6.luciferase as a control 2 weeks after MI. Echocardiography and LV hemodynamics were performed before and 6 weeks after gene transfer. Robust and long-term ßARKct expression was found after AAV6-mediated delivery, leading to significant amelioration of LV haemodynamics and contractile function in HF pigs compared with AAV6.luciferase-treated control animals that showed a continued decline in cardiac function. Interestingly, the neurohormonal axis was virtually normalized in AVV6.ßARKct-treated HF animals, represented by reductions in plasma norepinephrine levels, whereas AAV6.luciferase-treated pigs showed further increases in plasma catecholamine levels. As a result, LV remodelling and foetal gene expression was reversed by AVV6.ßARKct gene therapy. CONCLUSION: These data--showing sustained amelioration of cardiac function in a post-MI pig HF model--demonstrate the therapeutic potential of ßARKct gene therapy for HF.

Comparative Assessment of Percutaneous Left-Atrial Appendage Occlusion (LAAO) Devices-A Single Center Cohort Study.

BACKGROUND: Percutaneous left-atrial appendage closure (LAAC) is an established method for preventing strokes in patients with atrial fibrillation, offering an alternative to oral anticoagulation. Various occluder devices have been developed to cater to individual anatomical needs and ensure a safe and effective procedure. In this retrospective, monocentric cohort study, we compare different LAAO devices with respect to clinical outcomes, LAA sealing properties, and device-related complications. METHODS: We conducted a retrospective analysis of 270 patients who underwent percutaneous LAA closure in our center between 2009 and 2023. Patient data were extracted from medical records, including gender, age at implantation, indication, device type and size, laboratory values, LAA anatomy, periprocedural complications, ECG parameters, transthoracic and transesophageal echocardiography parameters (TTE and TEE), as well as medication at discharge. Moreover, fluoroscopy time and implantation duration, as well as post-implantation clinical events up to 1 year, were collected. Endpoints were bleeding events, recurrent stroke, thrombi on devices, and death. RESULTS: The implanted devices were the Watchman 2.5, Watchman FLX, Amplatzer Cardiac Plug (ACP), and Amulet. The procedural success rate was 95.7% (n = 265), with cactus anatomy posing the most challenges across all devices. The mean patient age was 75.5 ± 7.7 years, with 64.5% being male. The median CHA2DS2-VASc score was 4.8 ± 1.5 and the median HAS-BLED score was 3.8 ± 1.0. Indications for LAA closure included past bleeding events and elevated bleeding risk. Periprocedural complications were most commonly bleeding at the puncture site, particularly after ACP implantation (p = 0.014). Significant peridevice leaks (PDL) were observed in 21.4% of simple sealing mechanism devices versus 0% in double sealing mechanism devices (p = 0.004). Thrombi were detected on devices in six patients, with no subsequent ischemic stroke or thromboembolic event. Comparative analysis revealed no significant differences in the occurrence of stroke, transient ischemic attack (TIA), thromboembolic events, device-related thrombi, or mortality among different device types. A 62.3% relative risk reduction in thromboembolic events and 38.6% in major bleedings could be observed over 568.2 patient years. CONCLUSIONS: In summary, our study highlights the efficacy and safety of LAA closure using various occluder devices despite anatomical challenges. Our long-term follow-up findings support LAA closure as a promising option for stroke prevention in selected patient cohorts. Further research is needed to refine patient selection criteria and optimize outcomes in LAA closure procedures.

Prognostic relevance of global work index and global constructive work in patients with non-ischemic dilated cardiomyopathy.

Myocardial work (MW) derived from pressure-strain loops is a novel non-invasive tool to assess left ventricular (LV) function, incorporating global longitudinal strain (GLS) by speckle tracking echocardiography and non-invasively assessed blood pressure. Studies on the role of MW in dilated cardiomyopathy (DCM) are still limited. Therefore, the aim of this study was to evaluate the potential value of MW for predicting adverse outcomes in patients with DCM. 116 consecutive patients with DCM who underwent heart catheterization were retrospectively recruited from June 2009 to July 2014. 34 patients (30%) met the composite endpoints for major adverse cardiac events (MACE) of cardiac transplantation, need for implantable cardioverter-defibrillator (ICD) therapy, heart failure hospitalization and all-cause mortality. Patients with DCM were followed up for a mean of 5.1 years (IQR: 2.2-9.1 years). Global work index (GWI) and global constructive work (GCW) were not only independent predictors but also provided incremental predictive values (Integrated discrimination improvement [IDI] > 0) of MACE in multivariate Cox models. Furthermore, Patients with GWI < 788 mm Hg% (HR 5.46, 95%CI 1.66-17.92, p = 0.005) and GCW < 1,238 mm Hg% (HR 4.46, 95%CI 1.53-12.98, p = 0.006) had higher risks of MACE. GWI and GCW assessed by strain imaging echocardiography may have an additional value beyond LV-EF and GLS for predicting adverse outcomes in DCM.

Association of atrial myopathy in mitral valve disease on safety outcomes in left atrial appendage closure.

BACKGROUND: Patients undergoing left atrial appendage (LAA) occlusion (LAAO) are multi-morbid, including mitral valve disease (MVD) which is associated with anatomic changes of the left atrium (LA). This study aims to identify how atrial myopathy in MVD influences outcomes in LAAO. METHODS: Atrial myopathy in MVD was defined as LA diameter > 45 mm (♀) and > 48 mm (♂) and existing MVD or history of surgical/interventional treatment. Patients were compared with controls from the prospective, multicentre LAArge registry of LAAO. RESULTS: A total of 528 patients (52 MVD, 476 no-MVD) were included. The MVD group was significantly more likely to be older (78.2 years vs 75.9 years, p = 0.036) and female (59.6% vs 37.8%, p = 0.002). Altered LA anatomy was observed in MVD with significantly larger LA diameter (53 mm vs. 48 mm, p < 0.001) and LAA Ostia [at 135° 23.0 mm (20.5, 26.0) vs 20.0 mm (18.0, 23.0), p = 0.002]. Implant success was high with 96.2% and 97.9%, respectively, without differences in severe complications (7.7% vs 4.6%, p = 0.31). One-year mortality (17.8% vs 11.5%, p = 0.19) and a combined outcome of death, stroke, and systemic embolism (20.3% vs 12.4%, p = 0.13) were not different. Independent predictors of the combined outcome were peripheral artery disease (HR 2.41, 95% CI 1.46-3.98, p < 0.001) and chronic kidney disease (HR 3.46, 95% CI 2.02-5.93, p < 0.001) but not MVD and atrial myopathy. CONCLUSION: Patients with MVD present with altered LA anatomy with increased LA and LAA diameter. However, procedural success and safety in LAAO are not compromised. One-year mortality is numerically higher in patients with MVD but driven by comorbidities.

Improved procedural results after CoreValve implantation with the new AccuTrak delivery system.

AIMS OF THE STUDY: Transcatheter aortic valve implantation (TAVI) has become an established treatment for severe aortic stenosis in patients with unacceptable high-surgical risk. Recently, the new AccuTrak delivery system for improved deliverability of the CoreValve aortic bioprosthesis was launched. It has not yet been shown if the new delivery catheter leads to optimized positioning and improved procedural outcomes. METHODS AND RESULTS: We conducted a retrospective single-center analysis and evaluated 70 consecutive patients (35 with the original delivery catheter and 35 with the new AccuTrak catheter) for anatomic positioning and related outcome parameters like postinterventional aortic regurgitation (AR) and the need for permanent pacemaker insertion, after CoreValve implantation. The use of the AccuTrak delivery catheter resulted in significantly higher positioning of the CoreValve prosthesis in the left ventricular outflow tract (distance from annulus to lower edge of prosthesis 7.0 mm [5.5 to 9.4 mm] for the AccuTrak group vs. 8.8 mm [7.1 to 11.2 mm] for the original system; median [interquartile range]; P = 0.0068). Moreover, the optimized positioning resulted in reduced rates of significant (≥grade 2) AR assessed by postinterventional aortography and echocardiography (P = 0.044 and P = 0.0275, respectively). Despite improved positioning, no differences in the need for permanent pacemaker implantation were observed. CONCLUSIONS: Our retrospective analysis indicates improved positioning with reduced postinterventional AR with the new CoreValve AccuTrak delivery system. Whether this may also affect the need for permanent pacemaker insertion or long-term outcome after TAVI needs to be evaluated in larger studies.

Anticoagulation versus antiplatelet therapy after percutaneous left atrial appendage closure-subanalysis from the multicenter LAARGE registry.

PURPOSE: Data regarding post-procedural antithrombotic therapy following percutaneous left atrial appendage (LAA) in real-world populations using various occluder systems is limited. In the present analysis, anticoagulation (AC) was compared against antiplatelet therapy (APT) using data from the real-world multi-center LAARGE study. METHODS: Patients following LAA closure enrolled in the LAARGE study were assigned to two groups depending on initial post-implantation antithrombotic regime consisting of either AC or APT. Selection of antithrombotic medication was at the discretion of the treating center and/or physician. RESULTS: From July 2014 until January 2016, a total of 627 patients at 38 centers were included. A total of 75 patients (12%) received AC and 552 patients (88%) received APT, respectively. No significant differences were found between the groups regarding the composite of death, stroke and systemic embolism 1 year after LAA closure (Kaplan-Meier estimated rate 9.4% for AC vs. 12.8% for APT; p log rank = 0.45). With respect to bleeding events also, no differences were observed 1 year after the procedure (major bleeding 4.0% vs. 2.0%, p = 0.23; moderate bleeding 4.0% vs. 4.9%, p = 1.00; any bleeding 8.0% vs. 6.9%, p = 0.73). CONCLUSIONS: Postprocedural antithrombotic treatment with AC and APT showed comparable results regarding the composite of death, stroke, and systemic embolism as well as regarding bleeding complications after LAA closure in a real-world all-comers population.