Stable π-Extended Thio[7]helicene-Based Diradical with Predominant Through-Space Spin-Spin Coupling.

In this work, a novel π-extended thio[7]helicene scaffold was synthesized, where the α-position of the thiophene unit could be functionalized with bulky phenoxy radicals after considerable synthetic attempts. This open-shell helical diradical, ET7H-R, possesses high stability in the air, nontrivial π conjugation, persistent chirality, and a high diradical character (y0 of 0.998). The key feature is a predominant through-space spin-spin coupling (TSC) between two radicals at the helical terminals. Variable-temperature continuous-wave electron spin resonance (cw-ESR) and superconducting quantum interference device (SQUID) magnetometry in the solid state reveal a singlet ground state with a nearly degenerate triplet state of ET7H-R. These results highlight the significance of a stable helical diradicaloid as a promising platform for investigating intramolecular TSCs.

Synthesis and characterization of a formal 21-electron cobaltocene derivative.

Metallocenes are highly versatile organometallic compounds. The versatility of the metallocenes stems from their ability to stabilize a wide range of formal electron counts. To date, d-block metallocenes with an electron count of up to 20 have been synthesized and utilized in catalysis, sensing, and other fields. However, d-block metallocenes with more than formal 20-electron counts have remained elusive. The synthesis and isolation of such complexes are challenging because the metal-carbon bonds in d-block metallocenes become weaker with increasing deviation from the stable 18-electron configuration. Here, we report the synthesis, isolation, and characterization of a 21-electron cobaltocene derivative. This discovery is based on the ligand design that allows the coordination of an electron pair donor to a 19-electron cobaltocene derivative while maintaining the cobalt-carbon bonds, a previously unexplored synthetic approach. Furthermore, we elucidate the origin of the stability, redox chemistry, and spin state of the 21-electron complex. This study reveals a synthetic method, structure, chemical bonding, and properties of the 21-electron metallocene derivative that expands our conceptual understanding of d-block metallocene chemistry. We expect that this report will open up previously unexplored synthetic possibilities in d-block transition metal chemistry, including the fields of catalysis and materials chemistry.

6,6'-Biindeno[1,2-b]anthracene: An Open-Shell Biaryl with High Diradical Character.

We report in situ generation of a 6,6'-biindeno[1,2-b]anthracene (BIA) derivative as an open-shell biaryl with high diradical character, which could be identified by mass spectrometry, NMR spectroscopy, single-crystal X-ray analysis, UV-vis-NIR absorption spectroscopy, and electron paramagnetic resonance (EPR) spectroscopy. Theoretical calculations by various methods and variable-temperature EPR analyses were performed to tackle the elusive ground state of BIA diradical, suggesting a singlet ground state with a nearly degenerate triplet state. These results provide insight into the design of unique open-shell biaryls.

Direct observation of reversible bond homolysis by 2D EXSY NMR.

Bond homolysis is one of the most fundamental bond cleavage mechanisms. Thus, understanding of bond homolysis influences the development of a wide range of chemistry. Photolytic bond homolysis and its reverse process have been observed directly using time-resolved spectroscopy. However, direct observation of reversible bond homolysis remains elusive. Here, we report the direct observation of reversible Co-Co bond homolysis using two-dimensional nuclear magnetic resonance exchange spectroscopy (2D EXSY NMR). The characterization of species involved in this homolysis is firmly supported by diffusion ordered NMR spectroscopy (DOSY NMR). The unambiguous characterization of the Co-Co bond homolysis process enabled us to study ligand steric and electronic factors that influence the strength of the Co-Co bond. Understanding of these factors will contribute to rational design of multimetallic complexes with desired physical properties or catalytic activity.

Myasthenic crisis appearing after resection of intracardiac ectopic thymoma with superior vena cava syndrome.

BACKGROUND: We describe herein an extremely rare case of intracardiac ectopic thymoma-only two pure cases have been reported to date-associated with myasthenia gravis, an infrequent complication of ectopic thymoma. CASE PRESENTATION: A 71-year-old woman with superior vena cava syndrome was found to have a large mass mainly located in the right atrium. Tumor resection under cardiopulmonary bypass was performed. The pathological diagnosis was type AB ectopic thymoma. The postoperative course was complicated by progressive respiratory failure, and she was diagnosed with myasthenic crisis based on clinical signs and the edrophonium test. The patient recovered and was weaned from prolonged mechanical ventilation after receiving intravenous immunoglobulin, and was subsequently discharged uneventfully. CONCLUSIONS: This is the first report of myasthenic crisis due to intracardiac ectopic thymoma. Residual thymoma is a risk factor for the development of post-thymectomy myasthenia gravis, and long-term follow-up is required.

Perioperative management for iatrogenic aortocoronary dissection during percutaneous coronary intervention.

Aortocoronary dissection is a rare but serious complication. We report the case of a 72-year-old female with angina. Percutaneous coronary intervention was performed for right coronary artery disease. Manipulation of the guiding catheter led to aortocoronary dissection. A drug-eluting stent was immediately implanted in the right coronary ostium to seal the entry of the dissection. Computed tomography (CT) showed ascending aortic dissection. The patient was observed without surgery. CT performed the following day and showed the contrast in the false lumen which had disappeared. Clinicians are more likely to avoid surgical treatment if stenting successfully seals the entry of the coronary dissection.

[Transaortic Thoracic Endovascular Aortic Repair Via Right Anterior Mini-thoracotomy;Report of a Case].

An 81-year-old man presented with ruptured thoracic aortic aneurysm under stable condition. He had been suffering from chronic obstructive pulmonary disease, chronic renal failure and rheumatoid arthritis. We performed hybrid thoracic endovascular aortic repair via right anterior mini-thoracotomy inserting a device through a conduit on the ascending aorta. The patient was discharged without aorta-related complications.

Injectable Shear-Thinning Hydrogels for Minimally Invasive Delivery to Infarcted Myocardium to Limit Left Ventricular Remodeling.

BACKGROUND: Injectable, acellular biomaterials hold promise to limit left ventricular remodeling and heart failure precipitated by infarction through bulking or stiffening the infarct region. A material with tunable properties (eg, mechanics, degradation) that can be delivered percutaneously has not yet been demonstrated. Catheter-deliverable soft hydrogels with in vivo stiffening to enhance therapeutic efficacy achieve these requirements. METHODS AND RESULTS: We developed a hyaluronic acid hydrogel that uses a tandem crosslinking approach, where the first crosslinking (guest-host) enabled injection and localized retention of a soft (<1 kPa) hydrogel. A second crosslinking reaction (dual-crosslinking) stiffened the hydrogel (41.4±4.3 kPa) after injection. Posterolateral infarcts were investigated in an ovine model (n≥6 per group), with injection of saline (myocardial infarction control), guest-host hydrogels, or dual-crosslinking hydrogels. Computational (day 1), histological (1 day, 8 weeks), morphological, and functional (0, 2, and 8 weeks) outcomes were evaluated. Finite-element modeling projected myofiber stress reduction (>50%; P<0.001) with dual-crosslinking but not guest-host injection. Remodeling, assessed by infarct thickness and left ventricular volume, was mitigated by hydrogel treatment. Ejection fraction was improved, relative to myocardial infarction at 8 weeks, with dual-crosslinking (37% improvement; P=0.014) and guest-host (15% improvement; P=0.058) treatments. Percutaneous delivery via endocardial injection was investigated with fluoroscopic and echocardiographic guidance, with delivery visualized by magnetic resonance imaging. CONCLUSIONS: A percutaneous delivered hydrogel system was developed, and hydrogels with increased stiffness were found to be most effective in ameliorating left ventricular remodeling and preserving function. Ultimately, engineered systems such as these have the potential to provide effective clinical options to limit remodeling in patients after infarction.

Implantation of the Medtronic Harmony Transcatheter Pulmonary Valve Improves Right Ventricular Size and Function in an Ovine Model of Postoperative Chronic Pulmonary Insufficiency.

BACKGROUND: Pulmonary insufficiency is the nexus of late morbidity and mortality after transannular patch repair of tetralogy of Fallot. This study aimed to establish the feasibility of implantation of the novel Medtronic Harmony transcatheter pulmonary valve (hTPV) and to assess its effect on pulmonary insufficiency and ventricular function in an ovine model of chronic postoperative pulmonary insufficiency. METHODS AND RESULTS: Thirteen sheep underwent baseline cardiac magnetic resonance imaging, surgical pulmonary valvectomy, and transannular patch repair. One month after transannular patch repair, the hTPV was implanted, followed by serial magnetic resonance imaging and computed tomography imaging at 1, 5, and 8 month(s). hTPV implantation was successful in 11 animals (85%). There were 2 procedural deaths related to ventricular fibrillation. Seven animals survived the entire follow-up protocol, 5 with functioning hTPV devices. Two animals had occlusion of hTPV with aneurysm of main pulmonary artery. A strong decline in pulmonary regurgitant fraction was observed after hTPV implantation (40.5% versus 8.3%; P=0.011). Right ventricular end diastolic volume increased by 49.4% after transannular patch repair (62.3-93.1 mL/m2; P=0.028) but was reversed to baseline values after hTPV implantation (to 65.1 mL/m2 at 8 months, P=0.045). Both right ventricular ejection fraction and left ventricular ejection fraction were preserved after hTPV implantation. CONCLUSIONS: hTPV implantation is feasible, significantly reduces pulmonary regurgitant fraction, facilitates right ventricular volume improvements, and preserves biventricular function in an ovine model of chronic pulmonary insufficiency. This percutaneous strategy could potentially offer an alternative for standard surgical pulmonary valve replacement in dilated right ventricular outflow tracts, permitting lower risk, nonsurgical pulmonary valve replacement in previously prohibitive anatomies.

Unique Technique for Open Surgical Repair after Failed Endovascular Aneurysm Repair with Proximal Anastomoses.

Endovascular aortic aneurysm repair (EVAR) has revolutionized the management of abdominal aortic aneurysms (AAAs), with lower perioperative morbidity and mortality compared to conventional surgical repair. However, late secondary re-interventions after EVAR are still needed before aneurysm rupture in many cases. A patient with impending rupture of an AAA associated with a type I endoleak 7 years after EVAR who was successfully treated with a unique technique of fixation of the proximal aortic neck taking into account the structure of the stent graft is reported. This technique offers a safe solution to late open conversion after failed EVAR.

How Local Annular Force and Collagen Density Govern Mitral Annuloplasty Ring Dehiscence Risk.

BACKGROUND: Annuloplasty ring dehiscence is a well described mode of mitral valve repair failure. Defining the mechanisms underlying dehiscence may facilitate its prevention. METHODS: Factors that govern suture dehiscence were examined with an ovine model. After undersized ring annuloplasty in live animals (n = 5), cyclic force (FC) that acts on sutures during cardiac contraction was measured with custom transducers. FC was measured at ten suture positions, throughout cardiac cycles with peak left ventricular pressure (LVPmax) of 100, 125, and 150 mm Hg. Suture pullout testing was conducted on explanted mitral annuli (n = 12) to determine suture holding strength at each position. Finally, relative collagen density differences at suture sites around the annulus were assessed by two-photon excitation fluoroscopy. RESULTS: Anterior FC exceeded posterior FC at each LVPmax (eg, 2.8 ± 1.3 N versus 1.8 ± 1.2 N at LVPmax = 125 mm Hg, p < 0.01). Anterior holding strength exceeded posterior holding strength (6.4 ± 3.6 N versus 3.9 ± 1.6 N, p < 0.0001). On the basis of FC at LVPmax of 150 mm Hg, margin of safety before suture pullout was vastly higher between the trigones (exclusive) versus elsewhere (4.8 ± 0.9 N versus 1.9 ± 0.5 N, p < 0.001). Margin of safety exhibited strong correlation to collagen density (R(2) = 0.947). CONCLUSIONS: Despite lower cyclic loading on posterior sutures, the weaker posterior mitral annular tissue creates higher risk of dehiscence, apparently because of reduced collagen content. Sutures placed atop the trigones are less secure than predicted, because of a combination of reduced collagen and higher overall rigidity in this region. These findings highlight the inter-trigonal tissue as the superior anchor and have implications on the design and implantation techniques for next-generation mitral prostheses.

Effects of Age-Related Aortic Root Anatomic Changes on Left Ventricular Outflow Tract Pace-Mapping Morphologies: A Cardiac Magnetic Resonance Imaging Validation Study.

INTRODUCTION: Outflow tract ventricular arrhythmias (OT VAs) are common and catheter ablation is an effective treatment option. We sought to investigate the relationship between age-related anatomic aortic root changes and QRS morphology during left ventricular outflow tract (LVOT) pace-mapping using cardiac magnetic resonance (CMR) imaging. METHODS AND RESULTS: Fifty-one patients undergoing CMR imaging were divided into 3 groups based on age (<40, 40-60, >60 years). We measured the angle of the aortic root, the aorta to ventricular septal angle, the distance between the right coronary cusp (RCC) and left coronary cusp (LCC), and the distance between the ascending and descending aorta. Additionally, we evaluated the QRS morphologies obtained during pace-mapping from the LVOT. In older patients, LCC was more superior to the RCC (P < 0.01). Age was positively correlated with the aortic root angle (r2 = 0.481, P < 0.01) as well as the distances between the ascending and descending aorta at a level below the arch (r2 = 0.569, P < 0.01). In older patients, LVOT pace-mapping (performed in 16 patients) demonstrated higher maximal R-wave amplitude, and was greater when pacing from the LCC versus the RCC in lead III (1.8 ± 0.7 vs. 1.0 ± 0.5 mV, P = 0.02). CONCLUSION: The anatomy of the aortic root changes with age, and age-related aortic root changes may affect the QRS morphology during pace-mapping. Understanding the potential anatomic changes that accompany aging is important to maximize the efficacy of catheter ablation of OT VAs.

The Influence of Mitral Annuloplasty on Left Ventricular Flow Dynamics.

BACKGROUND: Mitral valve (MV) repair using annuloplasty rings is the preferred method of treatment for MV regurgitation, but the impact of annuloplasty ring placement on left ventricular intraventricular flow has not been studied. METHODS: Annuloplasty rings of varying sizes were placed in 5 healthy sheep (intercommissural ring sizes were 24, 26, 28, 30, and 32 mm), and three-dimensional phase contrast magnetic resonance imaging (4D flow MRI) was performed before and 1 week after ring placement. RESULTS: Normal diastolic flow consisted of diastolic intraventricular vortices that naturally unwound during systole. Postsurgical intraventricular flow was highly disturbed in all sheep, and the disturbance was greatest for undersized rings. Ring size was highly correlated with the diastolic inflow angle (Pearson's r = -0.62, p < 0.1, 95% confidence interval: -0.92 to 0.14). There was a mean angle increase of mean diastolic inflow angle increase of 12.3 degrees (< 30 mm, p < 0.01, 95% confidence interval: 4.8 to 19.6) for rings less than 30 mm. There was an inverse relationship between peak velocity and annuloplasty ring area (Pearson's r = -0.80, p < 0.05, 95% confidence interval: -0.96 to -0.2). Transmitral pressure gradients increased significantly from baseline 0.73 ± 0.18 mm Hg to after annuloplasty 2.31 ± 1.04 mm Hg (p < 0.05). CONCLUSIONS: Mitral valve annuloplasty ring placement disturbs normal left ventricular intraventricular flow patterns, and the degree of disturbance is closely associated with annuloplasty ring size.

Development of off-pump mitral valve replacement in a porcine model.

PURPOSE: We describe our initial experience with on-bypass and off-bypass (off-pump) mitral valve replacement with the modified version of our novel catheter-based sutureless mitral valve (SMV) technology, which was developed to atraumatically anchor and seal in the mitral position. DESCRIPTION: The SMV is a self-expanding device consisting of a custom designed nitinol framework and a pericardial leaflet valve mechanism. For the current studies, our original device was modified (SMV2) to reduce the delivery profile and to allow for controlled deployment while still maintaining the key principles necessary for atraumatic anchoring and sealing in the mitral valve position. EVALUATION: Ten Yorkshire pigs underwent successful SMV2 device implantation through a left atriotomy (on-pump, n = 6; off-pump, n = 4). Echocardiography and angiography revealed excellent left ventricular systolic function, no significant perivalvular leak, no mitral valve stenosis, no left ventricular outflow tract obstruction, and no aortic valve insufficiency. Postmortem examination demonstrated that the SMV2 devices were anchored securely. CONCLUSIONS: This study demonstrates the feasibility and short-term success of off-pump mitral valve replacement using a novel, catheter-based device in a porcine model.

Suture forces in undersized mitral annuloplasty: novel device and measurements.

PURPOSE: To demonstrate the first use of a novel technology for quantifying suture forces on annuloplasty rings to better understand the mechanisms of ring dehiscence. DESCRIPTION: Force transducers were developed, attached to a size 24 Physio ring, and implanted in the mitral annulus of an ovine animal. Ring suture forces were measured after implantation and for cardiac cycles reaching peak left ventricular pressures (LVP) of 100, 125, and 150 mm Hg. EVALUATION: After implantation of the undersized ring to the flaccid annulus, the mean suture force was 2.0±0.6 N. During cyclic contraction, the anterior ring suture forces were greater than the posterior ring suture forces at peak LVPs of 100 mm Hg (4.9±2.0 N vs 2.1±1.1 N), 125 mm Hg (5.4±2.3 N vs 2.3±1.2 N), and 150 mm Hg (5.7±2.4 N vs 2.4±1.1 N). The largest force was 7.4 N at 150 mm Hg. CONCLUSIONS: The preliminary results demonstrate trends in annuloplasty suture forces and their variation with location and LVP. Future studies will significantly contribute to clinical knowledge by elucidating the mechanisms of ring dehiscence while improving annuloplasty ring design and surgical repair techniques.

Real-time magnetic resonance imaging technique for determining left ventricle pressure-volume loops.

BACKGROUND: Rapid determination of the left ventricular (LV) pressure-volume (PV) relationship as loading conditions are varied is the gold standard for assessment of LV function. Cine magnetic resonance imaging (MRI) does not have sufficient spatiotemporal resolution to assess beat-to-beat changes of the LV PV relationship required to measure the LV end-systolic elastance (EES) or preload-recruitable stroke work (PRSW). Our aim was to investigate real-time MRI and semiautomated LV measurement of LV volume to measure PV relations in large animals under normal and inotropically stressed physiologic conditions. METHODS: We determined that PV relationships could be accurately measured using an image exposure time Tex less than 100 ms and frame rate Tfr less than 50 ms at elevated heart rates (∼140 beats per minute) using a golden angle radial MRI k-space trajectory and active contour segmentation. RESULTS: With an optimized exposure time (Tex=95 ms and frame rate Tfr=2.8 ms), we found that there was no significant difference between cine and real-time MRI at rest in end-diastolic volume, end-systolic volume, ejection fraction, stroke volume, or cardiac output (n=5, p<0.05) at either normal or elevated heart rates. We found EES increased from 1.9±0.7 to 3.1±0.3 mm Hg/mL and PRSW increased from 6.2±1.2 to 9.1±0.9 mm Hg during continuous intravenous dobutamine infusion (n=5, p<0.05). CONCLUSIONS: Real-time MRI can assess LV volumes, EES, and PRSW at baseline and elevated inotropic states.

Minimally invasive delivery of a novel direct epicardial assist device in a porcine heart failure model.

OBJECTIVE: Despite advances in design, modern ventricular assist device placement involves median sternotomy and cardiopulmonary bypass and is associated with infectious/embolic complications. In this study, we examine the feasibility and function of a novel minimally invasive, non-blood-contacting epicardial assist device in a porcine ischemic cardiomyopathy model. METHODS: Feasibility was first tested in an ex vivo thoracoscopic trainer box with slaughterhouse hearts. Five male Yorkshire swine underwent selective ligation of the circumflex artery to create a posterolateral infarct Twelve weeks after infarct, all animals underwent left minithoracotomy. A custom inflatable bladder was positioned over the epicardial surface of the infarct and firmly secured to the surrounding border zone myocardium with polypropylene mesh and minimally invasive mesh tacks. An external gas pulsation system actively inflated and deflated the bladder in synchrony with the cardiac cycle. All animals then underwent cardiac magnetic resonance imaging to assess ventricular function. RESULTS: All subjects successfully underwent off-pump placement of the epicardial assist device via minithoracotomy. Ejection fraction significantly improved from 29.1% ± 4.8% to 39.6% ± 4.23% (P < 0.001) when compared with pretreatment. End-systolic volume decreased (76.6 ± 13.3 mL vs 62.4 ± 12.0 mL, P < 0.001) and stroke volume increased (28.6 ± 3.4 mL vs 37.9 ± 3.1 mL, P < 0.05) when assisted. No change was noted in end-diastolic volume (105.1 ± 11.4 vs 100.3 ± 12.7). On postmortem examination, mesh fixation and device position were excellent in all cases. No adverse events were encountered. CONCLUSIONS: Directed epicardial assistance improves ventricular function in a porcine ischemic cardiomyopathy model and may provide a safe alternative to currently available ventricular assist device therapies. Further, the technique used for device positioning and fixation suggests that an entirely thoracoscopic approach is possible.

In-vivo mitral annuloplasty ring transducer: implications for implantation and annular downsizing.

Mitral annuloplasty has been a keystone to the success of mitral valve repair in functional mitral regurgitation. Understanding the complex interplay between annular-ring stresses and left ventricular function has significant implications for patient-ring selection, repair failure, and patient safety. A step towards assessing these challenges is developing a transducer that can be implanted in the exact method as commercially available rings and can quantify multidirectional ring loading. An annuloplasty ring transducer was developed to measure stresses at eight locations on both the in-plane and out-of-plane surfaces of an annuloplasty ring's titanium core. The transducer was implanted in an ovine subject using 10 sutures at near symmetric locations. At implantation, the ring was observed to undersize the mitral annulus. The flaccid annulus exerted both compressive (-) and tensile stresses (+) on the ring ranging from -3.17 to 5.34 MPa. At baseline hemodynamics, stresses cyclically changed and peaked near mid-systole. Mean changes in cyclic stress from ventricular diastole to mid-systole ranged from -0.61 to 0.46 MPa (in-plane direction) and from -0.49 to 1.13 MPa (out-of-plane direction). Results demonstrate the variability in ring stresses that can be introduced during implantation and the cyclic contraction of the mitral annulus. Ring stresses at implantation were approximately 4 magnitudes larger than the cyclic changes in stress throughout the cardiac cycle. These methods will be extended to ring transducers of differing size and geometry. Upon additional investigation, these data will contribute to improved knowledge of annulus-ring stresses, LV function, and the safer development of mitral repair techniques.

Directed epicardial assistance in ischemic cardiomyopathy: flow and function using cardiac magnetic resonance imaging.

BACKGROUND: Heart failure after myocardial infarction (MI) is a result of increased myocardial workload, adverse left ventricular (LV) geometric remodeling, and less efficient LV fluid movement. In this study we utilize cardiac magnetic resonance imaging to evaluate ventricular function and flow after placement of a novel directed epicardial assist device. METHODS: Five swine underwent posterolateral MI and were allowed to remodel for 12 weeks. An inflatable bladder was positioned centrally within the infarct and secured with mesh. The device was connected to an external gas exchange pump, which inflated and deflated in synchrony with the cardiac cycle. Animals then underwent cardiac magnetic resonance imaging during active epicardial assistance and with no assistance. RESULTS: Active epicardial assistance of the infarct showed immediate improvement in LV function and intraventricular flow. Ejection fraction significantly improved from 26.0% ± 4.9% to 37.3% ± 4.5% (p < 0.01). End-systolic volume (85.5 ± 12.7 mL versus 70.1 ± 11.9 mL, p < 0.01) and stroke volume (28.5 ± 4.4 mL versus 39.9 ± 3.1 mL, p = 0.03) were also improved with assistance. End-diastolic volume and regurgitant fraction did not change with treatment. Regional LV flow improved both qualitatively and quantitatively during assistance. Unassisted infarct regional flow showed highly discoordinate blood movement with very slow egress from the posterolateral wall. Large areas of stagnant flow were also identified. With assistance, posterolateral wall blood velocities improved significantly during both systole (26.4% ± 3.2% versus 12.6% ± 1.2% maximum velocity; p < 0.001) and diastole (54.3% ± 9.3% versus 24.2% ± 2.5% maximum velocity; p < 0.01). CONCLUSIONS: Directed epicardial assistance can improve LV function and flow in ischemic cardiomyopathy. This novel device may provide a valuable alternative to currently available heart failure therapies.