James J. Pilla

Cardiac Support Device Modifies Left Ventricular Geometry and Myocardial Structure After Myocardial Infarction

Background—Whether mechanical restraint of the left ventricle (LV) can influence remodeling after myocardial infarction (MI) remains poorly understood. This study surgically placed a cardiac support device (CSD) over the entire LV and examined LV and myocyte geometry and function after MI. Methods and Results—Post-MI sheep (35 to 45 kg; MI size, 23±2%) were randomized to placement of the CorCap CSD (Acorn Cardiovascular, Inc) (MI+CSD; n=6) or remained untreated (MI only; n=5). Uninstrumented sheep (n=10) served as controls. At 3 months after MI, LV end-diastolic volume (by MRI) was increased in the MI only group compared with controls (98±8 versus 43±4 mL; P<0.05). In the MI+CSD group, LV end-diastolic volume was lower than MI only values (56±7 mL; P<0.05) but remained higher than controls (P<0.05). Isolated LV myocyte shortening velocity was reduced by 35% from control values (P<0.05) in both MI groups. LV myocyte &bgr;-adrenergic response was reduced with MI but normalized in the MI+CSD group. LV myocyte length increased in the MI group and was reduced in the MI+CSD group. Relative collagen content was increased and matrix metalloproteinase-9 was decreased within the MI border region of the CSD group. Conclusions—A CSD beneficially modified LV and myocyte remodeling after MI through both cellular and extracellular mechanisms. These findings provide evidence that nonpharmacological strategies can interrupt adverse LV remodeling after MI.

A technique for in vivo mapping of myocardial creatine kinase metabolism

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 1H magnetic resonance spectroscopy. Results of CrEST studies from ex vivo myocardial tissue strongly correlate with results from 1H and 31P 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.

Stabilization of chronic remodeling by asynchronous cardiomyoplasty in dilated cardiomyopathy: effects of a conditioned muscle wrap.

BACKGROUND Dynamic cardiomyoplasty is a promising new therapy for dilated cardiomyopathy. The girdling effects of a conditioned muscle wrap alone have recently been postulated to partly explain its mechanism. We investigated this effect in a canine model of chronic dilated cardiomyopathy. METHODS AND RESULTS Twenty dogs underwent rapid ventricular pacing (RVP) for 4 weeks to create a model of dilated cardiomyopathy. Seven dogs were then randomly selected to undergo subsequent cardiomyoplasty, and all dogs had 6 weeks of additional RVP. The cardiomyoplasty group also received 6 weeks of concurrent skeletal muscle stimulation consisting of single twitches delivered asynchronously at 2 Hz to transform the wrap without active assistance. All dogs were studied by pressure-volume analysis and echocardiography at baseline and after 4 and 10 weeks of pacing. Systolic indices, including ejection fraction (EF), end-systolic elastance (Ees), and preload-recruitable stroke work (PRSW) were all increased at 10 weeks in the wrap versus controls (EF, 34.0 versus 27.1, P=.008; Ees, 1.65 versus 1.26, P=.09; PRSW, 35.9 versus 25.5, P=.001). Ventricular volumes, diastolic relaxation, and left ventricular end-diastolic pressures stabilized in the cardiomyoplasty group but continued to deteriorate in controls. Both the end-systolic and end-diastolic pressure-volume relationships shifted farther rightward in controls but remained stable in the cardiomyoplasty group. CONCLUSIONS In addition to potential benefits from active systolic assistance, benefits from dynamic cardiomyoplasty appear to be partially accounted for by the presence of a conditioned muscle wrap alone. This conditioned wrap stabilizes the remodeling process of heart failure, arresting progressive deterioration of systolic and diastolic function.

Deformation analysis of 3D tagged cardiac images using an optical flow method

BackgroundThis study proposes and validates a method of measuring 3D strain in myocardium using a 3D Cardiovascular Magnetic Resonance (CMR) tissue-tagging sequence and a 3D optical flow method (OFM).MethodsInitially, a 3D tag MR sequence was developed and the parameters of the sequence and 3D OFM were optimized using phantom images with simulated deformation. This method then was validated in-vivo and utilized to quantify normal sheep left ventricular functions.ResultsOptimizing imaging and OFM parameters in the phantom study produced sub-pixel root-mean square error (RMS) between the estimated and known displacements in the x (RMSx = 0.62 pixels (0.43 mm)), y (RMSy = 0.64 pixels (0.45 mm)) and z (RMSz = 0.68 pixels (1 mm)) direction, respectively. In-vivo validation demonstrated excellent correlation between the displacement measured by manually tracking tag intersections and that generated by 3D OFM (R ≥ 0.98). Technique performance was maintained even with 20% Gaussian noise added to the phantom images. Furthermore, 3D tracking of 3D cardiac motions resulted in a 51% decrease in in-plane tracking error as compared to 2D tracking. The in-vivo function studies showed that maximum wall thickening was greatest in the lateral wall, and increased from both apex and base towards the mid-ventricular region. Regional deformation patterns are in agreement with previous studies on LV function.ConclusionA novel method was developed to measure 3D LV wall deformation rapidly with high in-plane and through-plane resolution from one 3D cine acquisition.

Noninvasive Measurement of the Human Brachial Artery Pressure–Area Relation in Collapse and Hypertension

AbstractA noninvasive method to obtain pressure–lumen area (P-A) measurements of the human brachial artery is introduced. The data obtained from this method are analyzed using a mathematical model of the relationship between vessel pressure and lumen area including vessel collapse and hypertension. An occlusive arm cuff is applied to the brachial artery of ten normal subjects. The cuff compliance is determined continuously by means of a known external volume calibration pump. This permits the computation of the P-A curve of the brachial artery under the cuff. A model is applied to analyze the P-A relation of each subject. The results show that the lumen area varies considerably between subjects. The in vivo resting P-A curve of the brachial artery possesses features similar to that of in vitro measurements. A primary difference is that the buckling pressure is higher in vivo, presumably due to axial tension, as opposed to in vitro where it is near zero or negative. It is found that hypertension causes a shift in the P-A curve towards larger lumen areas. Also, the compliance–pressure curve is shown to shift towards higher transmural pressures. Increased lumen area provides an adaptive mechanism by which compliance can be maintained constant in the face of elevated blood pressure, in spite of diminished distensibility.

In vivo chronic myocardial infarction characterization by spin locked cardiovascular magnetic resonance.

BackgroundLate 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.Methods7Yorkshire 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.ResultsMean 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 < 0.05).T1ρ relaxation times were T1ρinfarct = 91.7 ms in the infarct and T1ρremote = 47.2 ms in the remote myocardium.ConclusionsT1ρ-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.

Rotating Frame Spin Lattice Relaxation in a Swine Model of Chronic, Left Ventricular Myocardial Infarction

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. Magn Reson Med, 2010.

Theoretic Impact of Infarct Compliance on Left Ventricular Function

BACKGROUND After coronary occlusion, the infarct region loses contractile function immediately and then undergoes a progressive healing process. This causes complex and time-dependent changes in infarct material properties that have not been well described experimentally. We used a theoretic approach to assess how infarct compliance effects left ventricular (LV) size and function after myocardial infarction. METHODS We used a closed-loop lumped-parameter model of the ovine cardiovascular system developed to study the effect of infarct size and compliance on cardiovascular function. The time-varying LV function was partitioned into infarct and noninfarct regions where the parameters of each could be adjusted separately. The model incorporated an adaptive compensatory mechanism to maintain stroke volume by varying the total blood volume. RESULTS For the preinfarction heart, the model produced pressure, volume, and functional results that were consistent with normal values for large animals. When infarcts of progressively larger size (5% to 25%) were introduced and stroke volume adaptation was permitted, the model produced pressure, volume, and functional results that were consistent with postinfarction values measured experimentally in large animals. Infarct size was held at 20% as infarct compliance decreased from 7 to 1 mL/mm Hg. This stiffening of the infarct resulted in reduced LV end-diastolic volume (200 to 60 mL), increased ejection fraction (0.10 to 0.30), and reduced LV end-diastolic pressure (14 to 5 mm Hg). Estimated LV oxygen consumption was also improved in the stiffer infracts. CONCLUSION Stiffer infarcts are associated with less LV dilatation, reduced filling pressures and better global LV function.

Ten weeks of rapid ventricular pacing creates a long-term model of left ventricular dysfunction.

OBJECTIVE Rapid ventricular pacing produces a reliable model of heart failure. Cessation after 4 weeks of rapid ventricular pacing results in rapid normalization of left ventricular function, but the left ventricle remains persistently dilated. We present novel data that show that prolonged rapid ventricular pacing (10 weeks) creates a model of chronic left ventricular dysfunction. METHODS In 9 dogs undergoing 10 weeks of rapid ventricular pacing, left ventricular function and volumes were serially assessed by using 2-dimensional echocardiography and pressure-volume analysis for 12 weeks after cessation of pacing. RESULTS Increased end-diastolic volume and decreased systolic and diastolic function were seen at the end of pacing. By 2 weeks of recovery from rapid ventricular pacing, end-diastolic volume and ejection fraction were partially recovered but did not improve further thereafter. Load-independent and load-sensitive indices of function obtained by pressure-volume analysis at 8 and 12 weeks of recovery confirmed a persistence of both systolic and diastolic dysfunction. In addition, left ventricular mass increased with pacing and remained elevated at 8 and 12 weeks of recovery. Four of these dogs studied at 6 months of recovery showed similar left ventricular abnormalities. CONCLUSION Ten weeks of rapid ventricular pacing creates a long-term model of left ventricular dysfunction.

Cardiac-respiratory gating method for magnetic resonance imaging of the heart

In studies of transmural myocardial function, acquisitions of high spatial and temporal resolution tagged cardiac images often exceed the practical time limit for breath‐hold fast imaging techniques. Therefore, a dual cardiac‐respiratory gating device has been constructed to acquire SPAMM‐tagged cardiac MR images at or near end‐expiration during spontaneous breathing, by providing an external trigger to a conventional MRI system. Combined cardiac and respiratory gating essentially eliminates the respiratory motion artifacts in tagged cardiac MR images. Compared to cardiac‐gated images obtained during intermittent breath‐holds, cardiac‐respiratory gated images show improved tag‐myocardium contrast due to magnetization recovery during inspiration. Magn Reson Med 43:314–318, 2000.