Angiotensin-converting enzyme inhibitor therapy affects left ventricular mass in patients with ejection fraction > 40% after acute myocardial infarction.

OBJECTIVES: We tested the hypothesis that angiotensin-converting enzyme (ACE) inhibitor therapy decreases left ventricular (LV) mass in patients with a left ventricular ejection fraction (LVEF) > 40% and no evidence of heart failure after their first acute Q wave myocardial infarction (MI). BACKGROUND: Recently, ACE inhibitor therapy has been shown to have an early mortality benefit in unselected patients with acute MI, including patients without heart failure and a LVEF > 35%. However, the effects on LV mass and volume in this patient population have not been studied. METHODS: Thirty-five patients with a LVEF > 40% after their first acute Q wave MI were randomized to titrated oral ramipril (n = 20) or conventional therapy (control, n = 15). Magnetic resonance imaging (MRI) performed an average of 7 days and 3 months after MI provided LV volumes and mass from summated serial short-axis slices. RESULTS: Left ventricular end-diastolic volume index did not change in ramipril-treated patients (62 +/- 16 [SD] to 66 +/- 17 ml/m2) or in control patients (62 +/- 16 to 68 +/- 17 ml/m2), and stroke volume index increased significantly in both groups. However, LV mass index decreased in ramipril-treated patients (82 +/- 18 to 73 +/- 19 g/m2, p = 0.0002) but not in the control patients (77 +/- 15 to 79 +/- 23 g/m2). Systolic arterial pressure did not change in either group at 3-month follow-up. CONCLUSIONS: In patients with a LVEF > 40% after acute MI, ramipril decreased LV mass, and blood pressure and LV function were unchanged after 3 months of therapy. Whether the decrease in mass represents a sustained effect that is associated with a decrease in morbid events requires further investigation.

A stable model of left ventricular dysfunction in an intact animal assessed with high fidelity pressure and cinemagnetic resonance imaging.

OBJECTIVE: Numerous models of acute and chronic left ventricular dysfunction have been used over the years. However, few can produce a rapid onset of global systolic and diastolic dysfunction that is stable and potentially reversible. The aim of this study was to develop such a model. METHODS: A model of left ventricular dysfunction was produced in six intact dogs using 1% halothane anaesthesia and pharmacological autonomic blockade with atropine (0.1 mg.kg-1) and propranolol (2 mg.kg-1). Left ventricular function was assessed by combined high fidelity pressure and cinemagnetic resonance imaging (cine-MR) during increases in afterload using infusions of angiotensin. RESULTS: Left ventricular systolic dysfunction was characterised by a diminished resting ejection fraction of 45(SD 4)% and a depressed +dP/dtmax of 1537(100) mm Hg.s-1. Diastolic dysfunction was manifested by an increased left ventricular end diastolic pressure of 16(2) mm Hg, a decreased -dP/dtmax of -1705(369) mm Hg.s-1, and a prolonged time constant of left ventricular relaxation of 42(9) ms. As left ventricular systolic pressure steadily rose with angiotensin infusion from 87(7) to 124(13) to 152(10) mm Hg (p < 0.001), left ventricular ejection fraction decreased markedly from 45(4) to 35(4) to 27(4)% (p < 0.001). Left ventricular +dP/dtmax did not change [1537(100) to 1500(110) to 1498(84) mm Hg.s-1] in spite of a significant increase in left ventricular end diastolic pressure from 16(2) to 21(5) to 29(7) mm Hg (p < 0.001) and left ventricular end diastolic volume from 59(12) to 71(14) to 78(17) ml (p < 0.001). Individual slopes of the end systolic pressure-volume relationship were also low, ranging between 2.1 and 4.4 mm Hg.s-1 (r = 0.99 to 1.00), typical of impaired contractility. CONCLUSIONS: Halothane anaesthesia in dogs pretreated with large amounts of propranolol and appropriate muscarinic cholinergic blockade produces a moderate decrease in baseline systolic and diastolic function in our intact dog model. However, left ventricular systolic function showed limited contractile reserve when challenged by physiological increases in systemic arterial pressure. Impaired systolic and diastolic function may, at least in part, be related to diminished activator calcium produced by halothane in addition to the well known negative inotropic action of beta adrenergic blockade.

The evolving role of MRI in the assessment of coronary artery disease.

Magnetic resonance imaging (MRI) methods are positioned to make a major impact in the care of patients with ischemic heart disease. Further advances are to be expected in the area of myocardial perfusion imaging and noninvasive MRI coronary "angiography." Work also continues in determining quantitative flow via MRI. Although expensive, the unique ability of MRI methods to provide multiple pieces of information in a single examination may make this technology cost effective. The concept of a "one-step shop" is progressing steadily toward a clinical reality.

Interstudy reproducibility of biplane cine nuclear magnetic resonance measurements of left ventricular function.

Cine nuclear magnetic resonance (NMR) imaging, as a noninvasive and high-resolution imaging modality, has been shown to be reliable for determining absolute left ventricular (LV) volumes and ejection fraction. A relatively new gradient echo cine NMR approach using 2 orthogonal long-axis planes (2- and 4-chamber) aligned with the true axes of the left ventricle has been previously developed and validated against radiographic biplane LV cineangiography. The aim of the present investigation was to determine the reproducibility of this more rapid cine NMR approach for the measurement of LV volumes and ejection fraction. Eighteen normal subjects underwent 2 cine NMR studies, on different days, using a 1.5-tesla clinical imaging system. Studies were analyzed on-line and blindly by 2 independent observers. Intraobserver error was also determined in a blinded manner. Mean values of measurements determined by this method in this group of normal subjects were end-diastolic volume (120 +/- 20 ml), end-systolic volume (39 +/- 9 ml) and ejection fraction (67 +/- 4%). Paired analysis of data revealed no significant bias between interstudy, interobserver or intraobserver measurements, except for interobserver end-diastolic volume, where the first observer measurements were slightly elevated (5.6 +/- 7.8 ml) compared with the second. This resulted in a small difference in ejection fraction (1.7 +/- 2.3%) between observers. The absolute variation between measurements (square root of variance components) was low for all interstudy, interobserver and intraobserver comparisons: end-diastolic volume was less than +/- 6.7 ml, end-systolic volume less than +/- 3.5 ml and ejection fraction less than +/- 2.4%.(ABSTRACT TRUNCATED AT 250 WORDS)

Accuracy of biplane long-axis left ventricular volume determined by cine magnetic resonance imaging in patients with regional and global dysfunction.

Left ventricular (LV) volumes and ejection fraction can be obtained by applying Simpson's rule to multiple short-axis tomographic planes. A simpler method for determining LV volumes using the area-length equation is widely accepted and requires less time to acquire and analyze. Its accuracy, however, is questionable in deformed or asymmetrically contracting ventricles. This study compares biplane long-axis to serial short-axis computed LV volumes obtained by cine gradient-echo magnetic resonance imaging (MRI) in 2 distinct patient populations: (1) patients with global LV dysfunction, and (2) patients with regional LV dysfunction. A total of 114 patients were studied using both methods. Among 37 patients with global LV dysfunction, there was no statistically significant difference between methods (long axis vs short axis) for determining LV end-diastolic volume (203 +/- 91 vs 201 +/- 90 ml), end-systolic volume (142 +/- 81 vs 141 +/- 82 ml), and ejection fraction (33 +/- 12 vs 33 +/- 13%). However, in the 77 patients with regional dysfunction, LV end-diastolic volume was statistically slightly higher when obtained using the long-axis approach (157 +/- 53 vs 152 +/- 51 ml; p=0.004). Otherwise, end-systolic volume (97 +/- 49 vs 95 +/- 49 ml) and ejection fraction (40 +/- 13 vs 40 +/- 13%) were similar (p=NS). The correlation between LV volumes and ejection fractions for both groups was excellent (r >0.91). Thus, in this study group, biplane long-axis and serial short-axis computed LV volumes and ejection fractions were similar in patients with global or regional LV dysfunction. In critically ill patients unable to complete a comprehensive MRI examination, the biplane long-axis-derived volumes provide adequate data.

The usefulness of cardiovascular magnetic resonance imaging.

Cardiovascular applications of magnetic resonance methods are now available clinically, and cost-effective strategies are being devised to bring this technology further into the clinical mainstream. Incorporation of magnetic resonance methods into the core curriculum of cardiovascular training programs is needed to provide practitioners with the necessary background to apply this exciting technology.

Assessment of ventricular volumes using cine magnetic resonance in the intact dog. A comparison of measurement methods.

UNLABELLED: RATIONALE, OBJECTIVE AND METHODS: The authors recently combined magnetic resonance imaging with high-fidelity left ventricular (LV) pressure measurement in a closed-chested, intact animal model. However, LV volumes derived from summated serial short axis slices require long imaging times and make it difficult to record LV volumes in response to acute alterations in load. In this study, geometry-based LV end-systolic volume estimates calculated from a single long-axis image (Area-Length formula) and from a long-axis and short-axis image (Bullet formula) were compared to those derived from summated short-axis images of the left ventricle (Simpson's rule) during altered loading conditions in six anesthetized, intact dogs. RESULTS: Angiotensin infusion produced three different LV systolic pressures (89 +/- 8 vs. 123 +/- 12 vs. 151 +/- 10 mmHg, P < .001). Area-Length and Bullet formula end-systolic volumes correlated with Simpson's rule volumes (r = .95 and .97; respectively). However, Bullet formula end-systolic volumes provided a significantly better agreement with Simpson's rule end-systolic volumes. CONCLUSIONS: The Bullet formula can be substituted for Simpson's rule to record magnetic resonance LV volumes during steady-state alterations in load in our intact animal model.

Right and left ventricular volumes and function after acute pulmonary hypertension in intact dogs.

A canine model was developed to record right (RV) and left ventricular (LV) volumes and high-fidelity pressures during acute pulmonary hypertension without the need for major surgery. In this study, new methodology was applied to record high-fidelity RV and LV pressures during cinemagnetic resonance imaging of the heart before and after acute pulmonary hypertension in six anesthetized intact dogs in which the pericardium and thorax were never disturbed by any surgical procedure. After pulmonary embolus, RV systolic pressure increased from 27 + 2 (SD) to 43 +/- 8 mmHg (P < 0.01) as LV systolic pressure decreased (97 +/- 17 to 76 +/- 3 mmHg; P < 0.05). Stroke volume (26 +/- 7 to 21 +/- 5 ml; P < 0.05) and RV ejection fraction (45 +/- 9 to 28 +/- 3%; P < 0.01) decreased as LV ejection fraction was unchanged (50 +/- 5 to 52 +/- 5%; P = NS). LV end-diastolic pressure decreased from 11 +/- 4 to 7 +/- 3 mmHg (P < 0.05), and RV end-diastolic pressure increased from 6 +/- 3 to 11 +/- 3 mmHg (P < 0.01). RV end-diastolic volume increased from 57 +/- 14 to 75 +/- 20 ml (P < 0.01) as LV end-diastolic volumes decreased from 53 +/- 11 to 42 +/- 10 ml (P < 0.01), resulting in no change in total ventricular volume at end diastole (111 +/- 24 to 116 +/- 28 ml). The observed mean decrease of 4.0 mmHg and 11 ml in LV end-diastolic pressure and volume, respectively, was associated with no change in total ventricular volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Adherence enhancers in pill-related clinical trials: a health behavior in cancer prevention model-based approach.

Preventing non-adherence and treating adherence failure are important to consider in designing community-based clinical trials. The approach and methods for managing adherence are vital. This paper describes a practical and theoretically-based strategy for managing adherence in a small cancer prevention trial with subjects (n = 40) taking a non-steroidal anti-inflammatory drug, piroxicam. Average daily pill intake adherence was exceptionally high (97.4%) as measured by self-report calendar. Thus, the generalized adherence enhancement approach used in this study may have been a related factor, although statistical model-testing was not possible in this small trial. The generalized intervention took into account factors such as the potential barriers and benefits of being in the study, self-efficacy and satisfaction with the participant/staff relationship. These and other theoretical variables were incorporated into an overall adherence strategy that is discussed.

Cardiac amyloidoma with IgM-kappa gammopathy.

A 73-year-old man presented with dyspnea and atrial flutter associated with an amyloid tumor in the heart. IgM-kappa gammopathy, hypercalcemia, and extensive cardiac and mediastinal invasion suggested a malignant lymphoid or plasma cell process. Although amyloidoma is generally considered to be a benign tumor, the aggressive features of this case mandated chemotherapy because the critical location rendered the tumor inoperable. This case provides noteworthy evidence in support of a possible pathogenic relationship between amyloidoma and plasmacytoma by virtue of dual representative features: localized amyloid infiltrated with plasma cells and the associated gammopathy. Local and systemic malignant features lend additional support to this hypothesis.

Evaluation of complex mediastinal masses by magnetic resonance imaging.

MRI was used to diagnose a mediastinal mass in a elderly patient with previous repair of aortic coarctation. MRI excluded aneurysm by demonstrating a homogeneous mass encasing aorta and the bypass graft. A second thoracotomy was avoided. Moreover, outpatient testing was performed, without exposure to contrast agents, ionizing radiation, or an invasive procedure.

An introduction to magnetic resonance methods for clinical research.

It is very early in the era of exploiting the power of magnetic resonance methods. Great strides have been made in both diagnostic medical imaging and spectroscopy. Using high field strength instruments, normal and abnormal biochemistry within specific CNS regions and their response to interventions ultimately may be discernible. With technological improvements, it is to be expected that image quality will improve, and in vivo spectroscopy may move rapidly from the research environment into the clinical arena.

Diagnosis and quantitation of myocardial infarction.

In order to provide timely and proper therapy for patients with myocardial infarction, accurate diagnosis is essential. To assess the impact of therapy and to aid in long-term prognostication, it is also desirable to quantitate accurately the extent of infarct size. For diagnostic purposes, the conventional methods of clinical evaluation, 12-lead electrocardiography, and analysis of serum enzymes are accurate. However, more sophisticated approaches, such as radionuclide, echocardiographic, and magnetic resonance imaging, can be useful adjuncts for diagnosis. In contrast, the sizing of infarcts is often best performed using imaging methods. This paper reviews the application of various techniques to accomplish the goals of accurate diagnosis and quantitation of myocardial infarction.

Block regional interpolation scheme for k-space (BRISK): a rapid cardiac imaging technique.

We introduce an acquisition method, "block regional interpolation scheme for k-space" (BRISK), to reduce the acquisition time for cardiac imaging. The method exploits the high degree of correlation that exists between time-resolved cardiac images. For representative k-space data sets, Fourier analysis was applied along the cardiac phase dimension to reveal that different regions of k-space can be effectively sampled at different rates. A reduced sampling strategy was implemented, and unsampled points were generated by Fourier interpolation. Time savings of up to 75% are quite feasible and 25% BRISK scans compare well with 100% scans. Simulations and acquisitions using a normal volunteer and patients are presented.

Multislice first-pass myocardial perfusion imaging on a conventional clinical scanner.

A technique is demonstrated for the acquisition and processing of multislice, first-pass contrast-enhanced perfusion images in the myocardium. The acquisition is a modification of "keyhole" imaging in which time series images are acquired by sampling a limited segment of k-space, corresponding to the low spatial frequencies. In the modification demonstrated here, keyhole samples are divided into two groups that are sampled on alternate cardiac cycles. The alternate "missing" k-space portions are synthesized by Fourier interpolation. Visualization of contrast agent accumulation by image subtraction is demonstrated. A motion artifact reduction process using time domain Fourier filtering is used to reduce artifacts from respiration. Studies were performed on 46 patients at 1.5 T using gadoteridol (0.05-0.1 mmol/kg) injected into the right antecubital vein in conjunction with radionuclide imaging. Fully concordant studies were noted in 27 of these patients. Remaining studies were either partially or completely discordant for reasons relating to the differing natures of radionuclide versus MR contrast agent characteristics.

Relationship between shortening load, contractility, and myocardial energetics in intact dog.

A canine model was developed to estimate left ventricular wall stress, volumes, contractility, and high-energy phosphate metabolites without the need for major surgery. A percutaneously inserted catheter-tip manometer was used to record high-fidelity left ventricular pressure while gradient echo cinemagnetic resonance (cine-MR) imaging alternated with in vivo 31P-nuclear magnetic resonance (NMR) spectroscopy during pharmacological maneuvers to increase cardiac work. Left ventricular circumferential wall stress, volumes, maximum rate of pressure development (dP/dtmax), and the ratio of phosphocreatine (PCr) to gamma-ATP (PCr/gamma-ATP) were recorded sequentially during control 1, dobutamine infusion, control 2, angiotensin infusion, and control 3 in five anesthetized, closed-chest dogs. PCr/gamma-ATP did not change significantly during controls 1-3, angiotensin, and dobutamine infusion. Left ventricular peak positive dP/dt (+dP/dtmax) increased significantly during dobutamine (3,338 +/- 831 mmHg/s, P < 0.001) but was unchanged during angiotensin (1,818 +/- 317 mmHg/s) and controls 1-3 (1,915 +/- 434 vs. 1,808 +/- 478 vs. 1,859 +/- 414 mmHg/s). However, dobutamine decreased the total systolic stress integral (area under the wall stress-time relationship) and end-diastolic and end-systolic volumes, whereas angiotensin increased these parameters compared with control conditions. The unchanged PCr/gamma-ATP is in accord with the results from other open-chest surface coil 31P-NMR experiments in the normal heart. Our assessment of left ventricular functional parameters provides new information that complements these more invasive studies in which heart rate-pressure product was measured during increases in cardiac work.(ABSTRACT TRUNCATED AT 250 WORDS)

Optimizing the method to calculate right ventricular ejection fraction from first-pass data acquired with a multicrystal camera.

BACKGROUND: The advantage of radionuclide angiographic techniques used to measure right ventricular ejection fraction (RVEF) is geometry independence, but the weakness is right atrial (RA) overlap. To minimize the effect of RA counts on right ventricular time activity curve (TAC), two regions of interest (ROI), one drawn for the end-diastolic image and one for the end-systolic image, are used for the calculation of RVEF from equilibrium gated blood pool scans (GBPS) and from gated first-pass studies with an Anger camera. A multicrystal camera offers both temporal separation of the bolus to the right side of the heart and good count statistics; therefore first-pass studies performed on a multicrystal camera theoretically should yield the most accurate measurements of RVEF, but few studies have been performed to validate RVEF against a reliable gold standard. METHODS AND RESULTS: To develop and validate an accurate method to measure RVEF from multicrystal first-pass data, 25 patients underwent sequential cine-MRI, first-pass radionuclide angiography, and gated equilibrium imaging. Five additional healthy volunteers underwent cine-MRI alone. Right and left ventricular volumes were measured from serial short axis cine-MRI views according to Simpson's rule. Three methods were used to calculate RVEF from first-pass data: a single ROI method, a dual ROI method, and a method in which a single ROI is applied to RA subtracted first-pass dynamic data. Five additional healthy volunteers underwent cine-MRI alone. When right ventricular stroke volume was plotted versus left ventricular stroke volume for the 5 volunteers and the 15 patients without valvular regurgitation, the regression line was not significantly different from the line of identity, supporting the accuracy of cine-MRI to measure RVEF. The RVEF by cine-MRI ranged from 34% to 59%; first-pass RVEF with a single ROI from 26% to 48%; first-pass RVEF with two ROIs from 31% to 59%; first-pass RVEF with RA subtracted single ROI from 29% to 60%; and RVEF from GBPS with multiple ROIs from 28% to 55%. The regressions for all three of the first-pass methods versus cine-MRI were significant (p < 0.01) as was the regression for the equilibrium GBPS versus cine-MRI but the correlation was weaker. The regressions for the 2-ROI method and for the RA subtracted single ROI method were not significantly different from the line of identity, whereas the regressions for both the single ROI method and for equilibrium GBPS were significantly different from the line of identity (p < 0.01). CONCLUSIONS: Cine-MRI can be used to validate radionuclide algorithms. Of the four radionuclide methods for measuring RVEF that were assessed, the first-pass 2-ROI method and the first-pass RA subtracted single ROI are the most accurate, the first-pass single ROI method underestimates RVEF, and the RVEF values measured from GBPS are less accurate.

Time-varying wall stress: an index of ventricular vascular coupling.

Previous work in the isolated heart and intact circulation has suggested that the relationship between wall stress and time during left ventricular (LV) ejection is linear and that the slope, which will be referred to as time-varying wall stress, increases in response to augmentation in afterload. However, the etiology of the increase in slope has not been determined in an intact animal. Magnetic resonance imaging coupled with high-fidelity LV pressure measurement using a nonferrous catheter-tip manometer generates a detailed assessment of wall stress in an animal model where the thorax and pericardium have never been disturbed. Accordingly, six anesthetized dogs were studied during autonomic blockade with atropine and propranolol during angiotensin infusion, producing three widely disparate left ventricular systolic pressures (87 +/- 7 vs. 124 +/- 13 vs. 152 +/- 10 mmHg, P less than 0.001). Time-varying wall stress did not change from low to medium load (-42.4 +/- 9.5 to -27.3 +/- 22.3 g.cm-2.ms-1) but increased significantly at high load (-21.7 +/- 14.9 g.cm-2.ms-1, P less than 0.05). Analysis of the relative contribution of pressure, chamber radius, wall thickness, and long-axis dimension to the changes in time-varying wall stress demonstrated only the pressure component to change its relative contribution at medium (P less than 0.001) and high load (P less than 0.001). Therefore, we conclude that the increase in time-varying wall stress results from augmentation of pressure in the latter one-half of systole that is incompletely offset by shortening and wall thickening.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in left ventricular mass and volumes in patients receiving angiotensin-converting enzyme inhibitor therapy for left ventricular dysfunction after Q-wave myocardial infarction.

OBJECTIVES: We evaluated global and segmental left ventricular (LV) mass and LV mass/volume ratio in patients with LV dysfunction receiving angiotensin-converting enzyme (ACE) inhibitor therapy after acute myocardial infarction (MI). BACKGROUND: ACE inhibitors attenuate LV dilatation and compensatory hypertrophy after acute MI in animal models. However, LV remodeling in patients after acute MI has been largely defined on the basis of changes in chamber volume alone. METHODS AND RESULTS: Twenty-nine patients with LV ejection fraction <40% received the ACE inhibitor ramipril (range 2.5 to 20 mg/day) within 5 days of their first Q-wave MI. Magnetic resonance imaging was performed at baseline and at 3 months, providing global and regional LV volumes and mass from summated serial short-axis slices. Mean arterial blood pressure was unchanged from baseline to 3-month follow-up (89 +/- 10 to 92 +/- 17 mm Hg). LV mass decreased (90 +/- 25 to 77 +/- 21 gm/m2, p < 0.0005) as LV end-diastolic volumes increased (65 +/- 13 to 73 +/- 22 ml/m2, p < 0.01). Global LV mass to volume ratio decreased from 1.40 +/- 0.28 to 1.08 +/- 0.18 gm/ml (p < 0.0001), as did circumferential wall thickness to volume ratio of noninfarcted myocardium at the base of the LV (0.06 +/- 0.02 to 0.05 +/- 0.02 mm/ml, p < 0.001). LV ejection fraction increased from 35 +/- 6 to 40 +/- 9% (p < 0.001) in the presence of an increase in calculated end-systolic wall stress (185 +/- 57 to 227 +/- 54 gm/cm2, p < 0.01). CONCLUSIONS: ACE inhibitor therapy was associated with improved LV function in the face of a decrease in mass to volume ratio of the LV as well as a decrease in wall thickness to volume ratio of noninfarcted myocardium. Whether ACE inhibitor therapy had direct or indirect effects on these changes in LV mass and function are open questions that require further investigation.