Cardiac MR Elastography: Comparison with left ventricular pressure measurement

Purpose of the Study: To compare magnetic resonance elastography (MRE) with ventricular pressure changes in an animal model. Methods: Three pigs of different cardiac physiology (weight, 25 to 53 kg; heart rate, 61 to 93 bpm; left ventricular [LV] end-diastolic volume, 35 to 70 ml) were subjected to invasive LV pressure measurement by catheter and noninvasive cardiac MRE. Cardiac MRE was performed in a short-axis view of the heart and applying a 48.3-Hz shear-wave stimulus. Relative changes in LV-shear wave amplitudes during the cardiac cycle were analyzed. Correlation coefficients between wave amplitudes and LV pressure as well as between wave amplitudes and LV diameter were determined. Results: A relationship between MRE and LV pressure was observed in all three animals (R-square [greater than or equal to] 0.76). No correlation was observed between MRE and LV diameter (R-square [less than or equal to] 0.15). Instead, shear wave amplitudes decreased 102 +/- 58 ms earlier than LV diameters at systole and amplitudes increased 175 +/- 40 ms before LV dilatation at diastole. Amplitude ratios between diastole and systole ranged from 2.0 to 2.8, corresponding to LV pressure differences of 60 to 73 mmHg. Conclusion: Externally induced shear waves provide information reflecting intraventricular pressure changes which, if substantiated in further experiments, has potential to make cardiac MRE a unique noninvasive imaging modality for measuring pressure-volume function of the heart

Assessment of Metabolic Phenotypes in Patients with Non-ischemic Dilated Cardiomyopathy Undergoing Cardiac Resynchronization Therapy

Studies of myocardial metabolism have reported that contractile performance at a given myocardial oxygen consumption (MVO2) can be lower when the heart is oxidizing fatty acids rather than glucose or lactate. The objective of this study is to assess the prognostic value of myocardial metabolic phenotypes in identifying non-responders among non-ischemic dilated cardiomyopathy (NIDCM) patients undergoing cardiac resynchronization therapy (CRT). Arterial and coronary sinus plasma concentrations of oxygen, glucose, lactate, pyruvate, free fatty acids (FFA), and 22 amino acids were obtained from 19 male and 2 female patients (mean age 56 ± 16) with NIDCM undergoing CRT. Metabolite fluxes/MVO2 and extraction fractions were calculated. Flux balance analysis (FBA) was performed with MetaFluxNet 1.8 on a metabolic network of the cardiac mitochondria (189 reactions, 230 metabolites) reconstructed from mitochondrial proteomic data (615 proteins) from human heart tissue. Non-responders based on left ventricular ejection fraction (LVEF) demonstrated a greater mean FFA extraction fraction (35% ± 17%) than responders [18 ± 10%, p = 0.0098, area under the estimated ROC curve (AUC) was 0.8238, S.E. 0.1115]. Calculated adenosine triphosphate (ATP)/MVO2 using FBA correlated with change in New York Heart Association (NYHA) class (rho = 0.63, p = 0.0298; AUC = 0.8381, S.E. 0.1316). Non-responders based on both LVEF and NYHA demonstrated a greater mean FFA uptake/MVO2 (0.115 ± 0.112) than responders (0.034 ± 0.030, p = 0.0171; AUC = 0.8593, S.E. 0.0965). Myocardial FFA flux and calculated maximal ATP synthesis flux using FBA may be helpful as biomarkers in identifying non-responders among NIDCM patients undergoing CRT

Simulation of dilated heart failure with continuous flow circulatory support

Lumped parameter models have been employed for decades to simulate important hemodynamic couplings between a left ventricular assist device (LVAD) and the native circulation. However, these studies seldom consider the pathological descending limb of the Frank-Starling response of the overloaded ventricle. This study introduces a dilated heart failure model featuring a unimodal end systolic pressure-volume relationship (ESPVR) to address this critical shortcoming. The resulting hemodynamic response to mechanical circulatory support are illustrated through numerical simulations of a rotodynamic, continuous flow ventricular assist device (cfVAD) coupled to systemic and pulmonary circulations with baroreflex control. The model further incorporated septal interaction to capture the influence of left ventricular (LV) unloading on right ventricular function. Four heart failure conditions were simulated (LV and bi-ventricular failure with/ without pulmonary hypertension) in addition to normal baseline. Several metrics of LV function, including cardiac output and stroke work, exhibited a unimodal response whereby initial unloading improved function, and further unloading depleted preload reserve thereby reducing ventricular output. The concept of extremal loading was introduced to reflect the loading condition in which the intrinsic LV stroke work is maximized. Simulation of bi-ventricular failure with pulmonary hypertension revealed inadequacy of LV support alone. These simulations motivate the implementation of an extremum tracking feedback controller to potentially optimize ventricular recovery. © 2014 Wang et al

Determinants of Bacteriophage 933W Repressor DNA Binding Specificity

We reported previously that 933W repressor apparently does not cooperatively bind to adjacent sites on DNA and that the relative affinities of 933W repressor for its operators differ significantly from that of any other lambdoid bacteriophage. These findings indicate that the operational details of the lysis-lysogeny switch of bacteriophage 933W are unique among lambdoid bacteriophages. Since the functioning of the lysis-lysogeny switch in 933W bacteriophage uniquely and solely depends on the order of preference of 933W repressor for its operators, we examined the details of how 933W repressor recognizes its DNA sites. To identify the specificity determinants, we first created a molecular model of the 933W repressor-DNA complex and tested the predicted protein-DNA interactions. These results of these studies provide a picture of how 933W repressor recognizes its DNA sites. We also show that, opposite of what is normally observed for lambdoid phages, 933W operator sequences have evolved in such a way that the presence of the most commonly found base sequences at particular operator positions serves to decrease, rather than increase, the affinity of the protein for the site. This finding cautions against assuming that a consensus sequence derived from sequence analysis defines the optimal, highest affinity DNA binding site for a protein

Effects of steroids and angiotensin converting enzyme inhibition on circumferential strain in boys with Duchenne muscular dystrophy: a cross-sectional and longitudinal study utilizing cardiovascular magnetic resonance

<p>Abstract</p> <p>Background</p> <p>Steroid use has prolonged ambulation in Duchenne muscular dystrophy (DMD) and combined with advances in respiratory care overall management has improved such that cardiac manifestations have become the major cause of death. Unfortunately, there is no consensus for DMD-associated cardiac disease management. Our purpose was to assess effects of steroid use alone or in combination with angiotensin converting enzyme inhibitors (ACEI) or angiotension receptor blocker (ARB) on cardiovascular magnetic resonance (CMR) derived circumferential strain (ε_cc).</p> <p>Methods</p> <p>We used CMR to assess effects of corticosteroids alone (Group A) or in combination with ACEI or ARB (Group B) on heart rate (HR), left ventricular ejection fraction (LVEF), mass (LVM), end diastolic volume (LVEDV) and circumferential strain (ε_cc) in a cohort of 171 DMD patients >5 years of age. Treatment decisions were made independently by physicians at both our institution and referral centers and not based on CMR results.</p> <p>Results</p> <p>Patients in Group A (114 studies) were younger than those in Group B (92 studies)(10 ± 2.4 vs. 12.4 ± 3.2 years, p < 0.0001), but HR, LVEF, LVEDV and LVM were not different. Although ε_ccmagnitude was lower in Group B than Group A (-13.8 ± 1.9 vs. -12.8 ± 2.0, p = 0.0004), age correction using covariance analysis eliminated this effect. In a subset of patients who underwent serial CMR exams with an inter-study time of ~15 months, ε_ccworsened regardless of treatment group.</p> <p>Conclusions</p> <p>These results support the need for prospective clinical trials to identify more effective treatment regimens for DMD associated cardiac disease.</p

Cardiac resynchronization therapy guided by cardiovascular magnetic resonance

Cardiac resynchronization therapy (CRT) is an established treatment for patients with symptomatic heart failure, severely impaired left ventricular (LV) systolic dysfunction and a wide (> 120 ms) complex. As with any other treatment, the response to CRT is variable. The degree of pre-implant mechanical dyssynchrony, scar burden and scar localization to the vicinity of the LV pacing stimulus are known to influence response and outcome. In addition to its recognized role in the assessment of LV structure and function as well as myocardial scar, cardiovascular magnetic resonance (CMR) can be used to quantify global and regional LV dyssynchrony. This review focuses on the role of CMR in the assessment of patients undergoing CRT, with emphasis on risk stratification and LV lead deployment