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Background LIVE (Less Invasive Ventricular Enhancement) with Revivent TC™ is an innovative therapy for symptomatic ischemic Heart Failure (HF). It is designed to reconstruct a negatively remodeled left ventricle (LV) after an anterior myocardial infarction (MI) by plication of the scar tissue. Its indications are specific and, as with any other structural heart intervention, the success of the procedure starts with appropriate patient selection. We aim to present the indications of the technique, crucial aspects in patient selection and individual case planning approach. Methods and Results After clinical evaluation, transthoracic echocardiography is the first imaging modality to be performed in a potential candidate for the therapy. However, definitive indication and detailed case planning rely on late gadolinium-enhanced cardiac magnetic resonance imaging or multiphasic contrast-enhanced cardiac computed tomography. These imaging modalities also assist with relative or absolute contra-indications for the procedure. Individual assessment is done to tailor the procedure to the specifics of the LV anatomy and location of the myocardial scar. Conclusion LIVE procedure is a unique intervention to treat symptomatic heart failure and ischemic cardiomyopathy after anterior MI. It is a highly customizable intervention that allows a patient-tailored approach, based on multimodality imaging assessment and planification.

Key message We mutated all seven Physcomitrium (Physcomitrella) patens phytochrome genes using highly-efficient CRISPR-Cas9 procedures. We thereby identified phy5a as the phytochrome primarily responsible for inhibiting gravitropism, proving the utility of the mutant library. Abstract The CRISPR-Cas9 system is a powerful tool for genome editing. Here we report highly-efficient multiplex CRISPR-Cas9 editing of the seven-member phytochrome gene family in the model bryophyte Physcomitrium (Physcomitrella) patens. Based on the co-delivery of an improved Cas9 plasmid with multiple sgRNA plasmids and an efficient screening procedure to identify high-order multiple mutants prior to sequencing, we demonstrate successful targeting of all seven PHY genes in a single transfection. We investigated further aspects of the CRISPR methodology in Physcomitrella, including the significance of spacing between paired sgRNA targets and the efficacy of NHEJ and HDR in repairing the chromosome when excising a complete locus. As proof-of-principle, we show that the septuple phy− mutant remains gravitropic in light, in line with expectations, and on the basis of data from lower order multiplex knockouts conclude that phy5a is the principal phytochrome responsible for inhibiting gravitropism in light. We expect, therefore, that this mutant collection will be valuable for further studies of phytochrome function and that the methods we describe will allow similar approaches to revealing specific functions in other gene families.

During this study, new Ni-base alloys precipitating cubic γ′ were developed which shall be used for the production of polycrystalline nanoporous membranes. The polycrystalline nanoporous membranes are produced through a combination of cold rolling and heat treatment in order to get directional coarsening of the γ′-phase which is selectively dissolved afterwards. Conventional Ni-based superalloys have a γ/γ′ -microstructure with cubic γ′-precipitates and show the needed etching behaviour but their high strength and limited ductility at room temperature do not allow to produce the polycrystalline nanoporous membranes by means of the before mentioned method. Thus, the new alloys with simpler composition were developed which have a γ/γ′ microstructure. The alloy Ni–13Fe–8Al–4Ti (composition in atomic percent) which was produced by Schmitz (Cullivier, ISBN 978-3-86955-523-2, 16) served as basis and showed the promising characteristics. To obtain cubic γ′-precipitates, the misfit was estimated to values of at least |0.2| % by a method presented by Mishima (Acta Metall 33:1161–1169, 23). Further, the phase compositions as well as phase volume fractions of γ-matrix and γ′-phase were calculated by means of Thermocalc® simulations (database: TTNi7). The etching behaviour of the new alloys was adjusted by adding chromium and molybdenum which passivate the γ-matrix so that the γ′-precipitates dissolve during the leaching process. The well-aligned cubic γ′-precipitates were obtained by partially replacing titanium by niobium. Furthermore, the hardness could be significantly lowered compared to conventional superalloys by reduction of alloying elements. Hence, the promising alloys were found to get directional coarsening of the γ′-precipitates in a combined process of cold rolling and heat treatment.

Background— Catheters are typically stiff and incorporate a pull-wire mechanism to allow tip deflection. While standing at the patient’s side, the operator manually navigates the catheter in the heart using fluoroscopic guidance. Methods and Results— A total of 42 patients (32 female; mean age, 55±15 years) underwent ablation of common-type (slow/fast) or uncommon-type (slow/slow) atrioventricular nodal reentrant tachycardia (AVNRT) with the use of the magnetic navigation system Niobe (Stereotaxis, Inc). It consists of 2 computer-controlled permanent magnets located on opposite sides of the patient, which create a steerable external magnetic field (0.08 T). A small magnet embedded in the catheter tip causes the catheter to align and to be steered by the external magnetic field. A motor drive advances or retracts the catheter, enabling complete remote navigation. Radiofrequency current was applied with the use of a remote-controlled 4-mm, solid-tip, magnetic navigation–enabled catheter (55°C, maximum 40 W, 60 seconds) in all patients. The investigators, who were situated in the control room, performed the ablation using a mean of 7.2±4.7 radiofrequency current applications (mean fluoroscopy time, 8.9±6.2 minutes; procedure duration, 145±43 minutes). Slow pathway ablation was achieved in 15 patients, whereas slow pathway modulation was the end point in the remaining patients. There were no complications. Conclusions— The Niobe magnetic navigation system is a new platform technology allowing remote-controlled navigation of an ablation catheter. In conjunction with a motor drive unit, this system was used successfully to perform completely remote-controlled mapping and ablation in patients with AVNRT.

OBJECTIVESThis study evaluates the feasibility and safety of a catheter-based laser system for percutaneous myocardial revascularization and analyses the first clinical acute and long-term results in patients with end-stage coronary artery disease (CAD) and severe angina pectoris.BACKGROUNDIn patients with CAD and intractable angina who are not candidates for either coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA), transmyocardial laser revascularization (TMR) has been developed as a new treatment that results in reduced angina pectoris and increased exercise capacity. However, surgical thoracotomy is required for TMR with considerable morbidity and mortality.METHODSA catheter-based system has been developed that allows creation of laser channels in the myocardium from within the left ventricular cavity. Laser energy generated by a Holmium: YAG (Cardiogenesis Corporation, Sunnyvale, California) laser was transmitted to the myocardium via a flexible optical fiber capped by an optic lens. The optical fiber was maneuvered to the target area under biplane fluoroscopy through a coaxial catheter system permitting movement in three dimensions.RESULTSThirty-four patients with severe CAD not amenable to either CABG or PTCA and refractory angina pectoris (Canadian Cardiologic Society [CCS] Angina Scale Class III–IV) were included in the study. Ischemic regions were identified by coronary angiography and confirmed by thallium scintigraphy. The percutaneous myocardial revascularization (PMR) procedure was successfully completed in all patients. In 29 patients, one vascular territory of the left ventricle and in 5 patients, two vascular territories were treated. Eight to fifteen channels were created in each ischemic region. Major periprocedural complications were limited to an episode of arterial bleeding requiring surgical repair. There was one death early after PMR, due to a myocardial infarction (MI) in a nontreated region. Clinical follow-up at 6 months (17 patients) demonstrated significant improvement of angina pectoris (CCS class before PMR: 3.0 ± 0.0, six months after PMR: 1.3 ± 0.8, p < 0.0001) and increased exercise capacity (exercise time on standard bicycle ergometry before PMR: 384 ± 141 s, six months after PMR: 514 ± 158 s, p < 0.05), but thallium scintigraphy failed to show improved perfusion of the laser treated regions.CONCLUSIONSPercutaneous myocardial revascularization is a new safe and feasible therapeutic option in patients with CAD and severe angina pectoris not amenable to either CABG or PTCA. Initial results show immediate and significant improvement of symptoms and exercise capacity but evidence of improved myocardial perfusion is still lacking.

The purpose of this study was to investigate the influence of different injury levels in persons with spinal cord injury (SCI) on epinephrine (Epi) and norepinephrine (NE) at rest and during graded wheelchair exercise and the related changes in heart rate and O2 uptake (V˙o 2). Twenty tetraplegics (Tetra), 10 high-lesion paraplegics (HLPara), 20 paraplegics with SCI below T5 (MLPara), and 18 able-bodied, nonhandicapped persons (AB) were examined. Because of the higher level of interruption of the sympathetic pathways, Tetra persons showed lower Epi and NE at rest and only slight increases during exercise compared with all other groups; the Tetra subjects’ impaired cardiac sympathetic innervation caused restricted cardioacceleration and strongly reduced maximalV˙o 2. When compared with AB persons, HLPara had comparable NE but lower Epi levels as a result of partial innervation of the noradrenergic system and denervation of the adrenal medulla. MLPara subjects showed an augmented basal and exercise-induced upper spinal thoracic sympathetic activity compared with AB subjects. The increase in heart rate in relation toV˙o 2 was higher in HLPara because of a smaller stroke volume as a result of venous blood pooling. The different exercise response in persons with SCI is a result of the interruption of pathways in the spinal cord to the peripheral sympathetic nervous system in addition to the motor paralysis.