The extravascular implantable cardioverter-defibrillator: characterization of anatomical parameters impacting substernal implantation and defibrillation efficacy.

AIMS: The aim of this study is to provide a thorough, quantified assessment of the substernal space as the site of extravascular implantable cardioverter-defibrillator (ICD) lead placement using computed tomography (CT) scans and summarizing adverse events and defibrillation efficacy across anatomical findings. Subcutaneous ICDs are an alternative to transvenous defibrillators but have limitations related to ICD lead distance from the heart. An alternative extravascular system with substernal lead placement has the potential to provide defibrillation at lower energy and pacing therapies from a single device. METHODS AND RESULTS: A multi-centre, non-randomized, retrospective analysis of 45 patient CT scans quantitatively and qualitatively assessing bony, cardiac, vascular, and other organ structures from two human clinical studies with substernal lead placement. Univariate logistic regression was used to evaluate 15 anatomical parameters for impact on defibrillation outcome and adjusted for multiple comparisons. Adverse events were summarized. Substernal implantation was attempted or completed in 45 patients. Defibrillation testing was successful in 37 of 41 subjects (90%) using ≥10 J safety margin. There were two intra-procedural adverse events in one patient, including reaction to anaesthesia and an episode of transient atrial fibrillation during ventricular fibrillation induction. Anatomical factors associated with defibrillation failure included large rib cage width, myocardium extending very posteriorly, and a low heart position in the chest (P-values <0.05), though not significant adjusting for multiple comparisons. CONCLUSION: Retrospective analysis demonstrates the ability to implant within the substernal space with low intra-procedural adverse events and high defibrillation efficacy despite a wide range of anatomical variability.

Short-term bone formation is greatest within high strain regions of the human distal radius: a prospective pilot study.

Bone adaptation is understood to be driven by mechanical strains acting on the bone as a result of some mechanical stimuli. Although the strain/adaptation relation has been extensively researched using in vivo animal loading models, it has not been studied in humans,likely due to difficulties in quantifying bone strains and adaptation in living humans. Our purpose was to examine the relationship between bone strain and changes in bone mineral parameters at the local level. Serial computed tomography (CT) scans were used to calculate 14 week changes in bone mineral parameters at the distal radius for 23 women participating in a cyclic in vivo loading protocol (leaning onto the palm of the hand), and 12 women acting as controls. Strains were calculated at the distal radius during the task using validated finite element (FE) modeling techniques. Twelve subregions of interest were selected and analyzed to test the strain/adaptation relation at the local level. A positive relationship between mean energy equivalent strain and percent change in bone mineral density (BMD) (slope=0.96%/1000 le, p<0.05) was observed within experimental,but not control subjects. When subregion strains were grouped by quartile, significant slopes for quartile versus bone mineral content (BMC) (0.24%/quartile) and BMD(0.28%/quartile) were observed. Increases in BMC and BMD were greatest in the highest-strain quartile (energy equivalent strain>539 le). The data demonstrate preliminary prospective evidence of a local strain/adaptation relationship within human bone.These methods are a first step toward facilitating the development of personalized exercise prescriptions for maintaining and improving bone health.

Quantifying Cardiothoracic Variation with Posture and Respiration to Inform Cardiac Device Design.

PURPOSE: With extravascular implantable cardioverter defibrillator leads placed beneath the sternum, it is important to quantify heart motion relative to the rib cage with postural changes and respiration. METHODS: MRI scans from five males and five females were collected in upright and supine postures at end inspiration [n = 10 each]. Left and right decubitus [n = 8 each] and prone [n = 5] MRIs at end inspiration and supine MRIs at end expiration [n = 5] were collected on a subset. Four cardiothoracic measurements, six cardiac measurements, and six cardiac landmarks were collected to measure changes across different postures and stages of respiration. RESULTS: The relative location of the LV apex to the nearest intercostal space was significantly different between the supine and decubitus postures (average ± SD difference: - 15.7 ± 11.4 mm; p < 0.05). The heart centroid to xipho-sternal junction distance was 9.7 ± 7.9 mm greater in the supine posture when compared to the upright posture (p < 0.05). Cardiac landmark motion in the lateral direction was largest due to postural movement (range 23-50 mm) from the left decubitus to the right decubitus posture, and less influenced by respiration (5-17 mm). Caudal-cranial displacement was generally larger due to upright posture (13-23 mm caudal) and inspiration (7-20 mm cranial). CONCLUSIONS: This study demonstrates that the location of the heart with respect to the rib cage varies with posture and respiration. The gravitational effects of postural shifts on the heart position are roughly 2-3 times larger than the effects of normal respiration.

Predicting surface strains at the human distal radius during an in vivo loading task--finite element model validation and application.

Bone strains resulting from physical activity are thought to be a primary driver of bone adaptation, but cannot be directly noninvasively measured. Because bone adapts nonuniformly, physical activity may make an important independent structural contribution to bone strength that is independent of bone mass and density. Our objective was to create and validate methods for subject-specific finite element (FE) model generation that would accurately predict the surface strains experienced by the distal radius during an in vivo loading task, and to apply these methods to a group of 23 women aged 23-35 to examine variations in strain, bone mass and density, and physical activity. Four cadaveric specimens were experimentally tested and specimen-specific FE models were developed to accurately predict periosteal surface strains (root mean square error=16.3%). In the living subjects, when 300 N load was simulated, mean strains were significantly inversely correlated with BMC (r=-0.893), BMD (r=-0.892) and physical activity level (r=-0.470). Although the group of subjects was relatively homogenous, BMD varied by two-fold (range: 0.19-0.40 g/cm(3)) and mean energy-equivalent strain varied by almost six-fold (range: 226.79-1328.41 µÎµ) with a simulated 300 N load. In summary, we have validated methods for estimating surface strains in the distal radius that occur while leaning onto the palm of the hand. In our subjects, strain varied widely across individuals, and was inversely related to bone parameters that can be measured using clinical CT, and inversely related to physical activity history.

In vivo loading model to examine bone adaptation in humans: a pilot study.

Bone is typically well suited for its habitual loading environment because of its ability to adapt. Although characteristics of the mechanical loading environment predict the bone adaptive response in animals, this has not been prospectively validated in humans. Here, we describe an in vivo loading model in which women apply forces to the radius by leaning onto their hand. We characterized the strain environment imposed on the radius using cadaveric experimentation and conducted a prospective study in which 19 adult women loaded their distal radii 50 cycles/day, 3 days/week, for 28 weeks and seven additional adult women served as controls. In four cadaveric specimens, loading caused compressive principal strains of -1,695 ± 396 µÎµ with radial bending dorsally and towards the ulna. Prospective in vivo loading produced measurable improvements to bone and appeared to protect against bone loss associated with seasonal fluctuations in physical activity and sun exposure. Experimental subjects had significant gains to bone volume (BV) and moments of inertia, while, control subjects had significant losses in BMC and moments of inertia. The loading model is thus suitable as a model system for exploring bone adaptation in humans, and may eventually be clinically useful for strengthening the radius of women.