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This study was to evaluate the effects of ischemic mitral regurgitation (IMR) on vortex formation and leaflet dynamics using an established porcine infarct model of IMR. Using direct coronary ligation, five animals were subjected to a posterolateral myocardial infarction (MI) followed by an MRI at 12-weeks post MI. MR imaging consisted of 4D time-resolved left ventricular (LV) flow, full coverage 2D LV cine, and high resolution 2D cine of mitral valve dynamics. Five additional naive animals underwent identical imaging protocols to serve as controls. Image analysis was performed to obtain mitral transvalvular flows as well as LV volumes throughout the cardiac cycle. In addition, anterior to posterior mid-leaflet tip distances were measured throughout the cardiac cycle for determination of temporal leaflet dynamics. It was found IMR caused asymmetric vortex ring formation with the anterior vortex having a lower vorticity relative to its posterior counterpart. In contrast, normal ventricles create symmetric and tightly curled vortices in the basal chamber just underneath the mitral leaflets which conserve kinetic energy and aid in effective ejection. IMR animals were also evaluated for leaflet separation and were found to have a greater leaflet opening and achieved peak vorticity and peak leaflet opening later than control animals. In conclusion, this study shows the effects that altered vortex formation, due to IMR, can have on ventricular filling and leaflet dynamics. These findings have important implications for understanding blood flow through the dilated heart and how ring annuloplasty and volume reduction interventions may influence mitral valve dynamics.

ObjectiveDespite 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.MethodsFeasibility 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.ResultsAll 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.ConclusionsDirected 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.

Mammalian organs continually exchange metabolites via circulation, but systems-level analysis of this shuttling process is lacking. Here, we compared, in fasted pigs, metabolite concentrations in arterial blood versus draining venous blood from 11 organs. Greater than 90% of metabolites showed arterial-venous differences across at least one organ. Surprisingly, the liver and kidneys released not only glucose but also amino acids, both of which were consumed primarily by the intestine and pancreas. The liver and kidneys exhibited additional unexpected activities: liver preferentially burned unsaturated over more atherogenic saturated fatty acids, whereas the kidneys were unique in burning circulating citrate and net oxidizing lactate to pyruvate, thereby contributing to circulating redox homeostasis. Furthermore, we observed more than 700 other cases of tissue-specific metabolite production or consumption, such as release of nucleotidesby the spleen and TCA intermediates bypancreas. These data constitute a high-value resource, providing a quantitative atlas of inter-organ metabolite exchange.

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/m 2 ; P =0.028) but was reversed to baseline values after hTPV implantation (to 65.1 mL/m 2 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.

T1ρ relaxation times were quantified in a swine model of chronic, left ventricular myocardial infarction. It was found that there were low frequency relaxation mechanisms that suppress endogenous contrast at low spin-lock amplitudes and in T2-weighted images. A moderate amplitude spin-locking pulse could overcome these relaxation mechanisms. Relaxation dispersion data were measured over a range of RF field amplitudes, and a model was formulated to include dipole-dipole relaxation modulated by molecular rotation and an apparent exchange mechanism. These techniques may find some use in the clinic for the observation of chronic, left ventricular cardiac remodeling.

Introduction: Chronic postoperative pulmonary insufficiency (PPI) is the major cause of long-term morbidity and mortality in patients (pts) with tetralogy of Fallot (TOF). Pulmonary valve replacement (PVR) can mitigate the risk, but optimal timing for PVR remains controversial. Time-resolved 3D phase-contrast MRI (4DF) provides insight into complex intracardiac flow patterns. 4DF may help inform management decisions regarding timing of PVR. We describe the first quantitative serial 4DF analysis in an ovine model of PPI. Methods: A baseline cardiac MRI (CMRI) was performed on four Dorsett sheep (36-39kg) on a 3-Tesla Siemens scanner. Following baseline MRI, animals underwent pulmonary valvectomy and transannular patch (TAP) placement yielding PPI. Follow-up CMRI were obtained at 5mo and 7mo post-valvectomy (PoVa). Pathlines were emitted from a circular region of interest (ROI) representing the pulmonary valve annulus. Velocities, flow rate, and stresses were obtained throughout a complete cardiac cycle and compared across time. Results: Systolic max velocity, average velocity, and flow rate normal to the ROI plane decreased over time. Diastolic velocities increased at 5mo before decreasing at 7mo PoVa. Regurgitant flow was observed in diastole PoVa , and regurgitant flow rate increased with time. The max and average component of shear stress (viscosity = 3 cP) along the pulmonary artery wall decreased over time in systole. In diastole, shear stress increased at 5mo and decreased at 7mo. Parameters plotted in Figure 1. Conclusion: 4DF provides a new method for visualization and quantification of alterations in blood flow patterns in the right side of the heart in an ovine model of PPI. Alterations in above parameters may indicate myocardial and pulmonary vascular deterioration precedent to morphological changes. Characterization of altered flow patterns in human pts with TOF may help to ultimately inform decisions regarding timing of PVR.

Author(s): Contijoch, Francisco; Witschey, Walter R; McGarvey, Jeremy R; Levack, Melissa M; Ferrari, Victor A; Kondo, Norihiro; Takebayashi, Satoshi; Shimaoka, Toru; Aoki, Chikashi; Zsido, Gerald A; Gorman, Joseph H; Gorman, Robert C; Pilla, James J

ATP derived from the conversion of phosphocreatine to creatine by creatine kinase provides an essential chemical energy source that governs myocardial contraction. Here, we demonstrate that the exchange of amine protons from creatine with protons in bulk water can be exploited to image creatine through chemical exchange saturation transfer (CrEST) in myocardial tissue. We show that CrEST provides about two orders of magnitude higher sensitivity compared to (1)H magnetic resonance spectroscopy. Results of CrEST studies from ex vivo myocardial tissue strongly correlate with results from (1)H and (31)P magnetic resonance spectroscopy and biochemical analysis. We demonstrate the feasibility of CrEST measurement in healthy and infarcted myocardium in animal models in vivo on a 3-T clinical scanner. As proof of principle, we show the conversion of phosphocreatine to creatine by spatiotemporal mapping of creatine changes in the exercised human calf muscle. We also discuss the potential utility of CrEST in studying myocardial disorders.

Background Late gadolinium enhanced (LGE) cardiovascular magnetic resonance (CMR) is frequently used to evaluate myocardial viability, estimate total infarct size and transmurality, but is not always straightforward is and contraindicated in patients with renal failure because of the risk of nephrogenic systemic fibrosis. T2- and T1-weighted CMR alone is however relatively insensitive to chronic myocardial infarction (MI) in the absence of a contrast agent. The objective of this manuscript is to explore T1ρ-weighted rotating frame CMR techniques for infarct characterization without contrast agents. We hypothesize that T1ρ CMR accurately measures infarct size in chronic MI on account of a large change in T1ρ relaxation time between scar and myocardium. Methods 7Yorkshire swine underwent CMR at 8 weeks post-surgical induction of apical or posterolateral myocardial infarction. Late gadolinium enhanced and T1ρ CMR were performed at high resolution to visualize MI. T1ρ-weighted imaging was performed with a B1 = 500 Hz spin lock pulse on a 3 T clinical MR scanner. Following sacrifice, the heart was excised and infarct size was calculated by optical planimetry. Infarct size was calculated for all three methods (LGE, T1ρ and planimetry) and statistical analysis was performed. T1ρ relaxation time maps were computed from multiple T1ρ-weighted images at varying spin lock duration. Results Mean infarct contrast-to-noise ratio (CNR) in LGE and T1ρ CMR was 2.8 ± 0.1 and 2.7 ± 0.1. The variation in signal intensity of tissues was found to be, in order of decreasing signal intensity, LV blood, fat and edema, infarct and healthy myocardium. Infarct size measured by T1ρ CMR (21.1% ± 1.4%) was not significantly different from LGE CMR (22.2% ± 1.5%) or planimetry (21.1% ± 2.7%; p infarct = 91.7 ms in the infarct and T1ρremote = 47.2 ms in the remote myocardium. Conclusions T1ρ-weighted imaging using long spin locking pulses enables high discrimination between infarct and myocardium. T1ρ CMR may be useful to visualizing MI without the need for exogenous contrast agents for a wide range of clinical cardiac applications such as to distinguish edema and scar tissue and tissue characterization of myocarditis and ventricular fibrosis.

Background Mitral valve repair (MVR) shows clinical and economic superiority over mitral valve replacement in patients with dystrophic and rheumatic regurgitation, but outcomes are less certain in chronic ischemic mitral regurgitation (IMR). We hypothesize that MVR may have adverse effects on LV hemodynamics resulting from suboptimal annuloplasty geometry and post-repair mitral valve stenosis whose consequences are most acutely felt in IMR patients because of their impaired LV function. To test this hypothesis, we qualitatively described post-repair hemodynamics and measured LV inflow quantities (peak diastolic inflow velocity, transmitral pressure, and inflow angle) after MVR in sheep. Methods

Background Leaflet malcoaptation in ischemic mitral regurgitation (IMR) is thought to be caused by a combination of annular dilatation and leaflet tethering due to subvalvular ventricular remodeling. Despite this, little is known regarding leaflet dynamics in IMR. Using high temporal resolution MRI we describe, for the first time, the influence of post infarction ventricular remodeling on leaflet motion.

Results Both fBP and kwicSense were found to increase the overall stroke volume by 5-6 mL compared to cine-SSFP acquisitions during free-breathing resting state conditions. The measured LVESV were similar for the three methods: 63.4 mL (kwicSense), 64.4 mL (fBP) and 65.9 mL (cine-bSSFP), although LVEDV was greater for the real time methods: 91.3 mL (kwicSense), 92.9 (fBP) and 89.4 (cine-SSFP). Small variations between segmentation of the volumes resulted in a left or right shift of the PV loop, although the shape of the loop, and consequently total myocardial work, was consistent. Blurring associated with the fBP method resulted in a greater myocardial signal intensity deteriorating the quality of image segmentation. Variations in the stroke volume may be related to changes in preload between cine-SSFP and real time acquisitions in the anesthetized animal. Conclusions Real time MRI methods show great potential to characterize pre- and afterload independent indices of reduced cardiac contractile performance and hemodynamic dysfunction.