Robert W Biederman

Myocardial First-Pass Perfusion Magnetic Resonance Imaging A Multicenter Dose-Ranging Study

Background—MRI can identify patients with obstructive coronary artery disease by imaging the left ventricular myocardium during a first-pass contrast bolus in the presence and absence of pharmacologically induced myocardial hyperemia. The purpose of this multicenter dose-ranging study was to determine the minimally efficacious dose of gadopentetate dimeglumine injection (Magnevist Injection; Berlex Laboratories) for detecting obstructive coronary artery disease. Method and Results—A total of 99 patients scheduled for coronary artery catheterization as part of their clinical evaluation were enrolled in this study. Patients were randomized to 1 of 3 doses of gadopentate dimeglumine: 0.05, 0.10, or 0.15 mmol/kg. First-pass perfusion imaging was performed during hyperemia (induced by a 4-minute infusion of adenosine at a rate of 140 &mgr;g · kg−1 · min−1) and then again in the absence of adenosine with otherwise identical imaging parameters and the same contrast dose. Perfusion defects were evaluated subjectively by 4 blinded reviewers. Receiver-operating curve analysis showed that the areas under the receiver-operating curve were 0.90, 0.72, and 0.83 for the low-, medium-, and high-contrast doses, respectively, compared with quantitative coronary angiography (diameter stenosis ≥70%). For the low-dose group, mean sensitivity was 93±0%, mean specificity was 75±7%, and mean accuracy was 85±3%. Conclusions—First-pass perfusion MRI is a safe and accurate test for identifying patients with obstructive coronary artery disease. A low dose of 0.05 mmol/kg gadopentetate dimeglumine is at least as efficacious as higher doses.

Role of Cardiac Magnetic Resonance Imaging in the Management of Patients With Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by abnormally elevated blood pressure of the pulmonary circulation that results, over time, from extensive vascular remodeling and increased pulmonary vascular resistance. Recent advances in magnetic resonance imaging (MRI) technology have led to the development of techniques for noninvasive assessment of cardiovascular structure and function, including hemodynamic parameters in the pulmonary circulation, which are superior in their identification of right ventricular morphologic changes. These advantages make cardiac MRI an attractive modality for following up and providing prognoses in patients with PAH. In this review, we summarize recent developments in the use of MRI for the diagnosis, assessment, and ongoing monitoring of patients with PAH. Over the coming decade, it can be anticipated that continued improvements in MRI image acquisition, spatial and temporal resolution, and analytical techniques will result in improved understanding of PAH pathophysiology, diagnosis, and prognostic variables, and will supplement, and may even replace, some of the invasive procedures currently applied routinely to the evaluation of PAH.

The impact of myocardial flow reserve on the detection of coronary artery disease by perfusion imaging methods: an NHLBI WISE study.

Myocardial flow reserve (MFR) is not routinely assessed in myocardial perfusion imaging (MPI) studies but has been hypothesized to affect test accuracy when assessing disease severity by coronary vessel lumenography. Magnetic resonance imaging (MRI) is an emerging diagnostic technique that can both perform MPI and assess MFR. We studied women (n = 184) enrolled in the Womens Ischemia Syndrome Evaluation (WISE) study with symptoms suggesting ischemic heart disease. Tests performed were coronary angiography and MPI by both MR and gated radionuclide single photon emission computed tomography (gated-SPECT). The MFR index was calculated using the MR data acquired at baseline and under vasodilation (dipyridamole) conditions. The study was structured with a pilot and an implementation phase. During the pilot phase (n = 46) data were unmasked and an MFR threshold was defined to divide patients into those with an adequate (AMFRI) or inadequate (IMFRI) MFR index. During the implementation phase, the MFR index threshold was prospectively applied to patients (n = 138). In the implementation phase, MPI ischemia detection accuracy compared to severe (> or = 70%) coronary artery diameter narrowing by angiography was higher in the AMFRI vs. the IMFRI group for MRI (86% vs. 70%, p < 0.05) and gated-SPECT (89% vs. 67%, p < 0.01). The IMFRI group (n = 55, 30% of study population) had a higher resting rate-pressure product compared with the AMFRI group (10,599 +/- 2871 vs. 9378 +/- 2447 bpm mm Hg, p < 0.01), consistent with higher resting myocardial flow. When compared with each other, MRI and gated-SPECT MPI showed no difference in accuracy among MFR groups. Myocardial perfusion patterns in the IMFRI group may have resulted in atypical perfusion patterns, which either masked or mimicked epicardial coronary artery disease.

Assessing the Risks Associated with MRI in Patients with a Pacemaker or Defibrillator

Background The presence of a cardiovascular implantable electronic device has long been a contraindication for the performance of magnetic resonance imaging (MRI). We established a prospective registry to determine the risks associated with MRI at a magnetic field strength of 1.5 tesla for patients who had a pacemaker or implantable cardioverter–defibrillator (ICD) that was “non–MRI‐conditional” (i.e., not approved by the Food and Drug Administration for MRI scanning). Methods Patients in the registry were referred for clinically indicated nonthoracic MRI at a field strength of 1.5 tesla. Devices were interrogated before and after MRI with the use of a standardized protocol and were appropriately reprogrammed before the scanning. The primary end points were death, generator or lead failure, induced arrhythmia, loss of capture, or electrical reset during the scanning. The secondary end points were changes in device settings. Results MRI was performed in 1000 cases in which patients had a pacemaker and in 500 cases in which patients had an ICD. No deaths, lead failures, losses of capture, or ventricular arrhythmias occurred during MRI. One ICD generator could not be interrogated after MRI and required immediate replacement; the device had not been appropriately programmed per protocol before the MRI. We observed six cases of self‐terminating atrial fibrillation or flutter and six cases of partial electrical reset. Changes in lead impedance, pacing threshold, battery voltage, and P‐wave and R‐wave amplitude exceeded prespecified thresholds in a small number of cases. Repeat MRI was not associated with an increase in adverse events. Conclusions In this study, device or lead failure did not occur in any patient with a non–MRI‐conditional pacemaker or ICD who underwent clinically indicated nonthoracic MRI at 1.5 tesla, was appropriately screened, and had the device reprogrammed in accordance with the prespecified protocol. (Funded by St. Jude Medical and others; MagnaSafe ClinicalTrials.gov number, NCT00907361.)

Prognostic value of global MR myocardial perfusion imaging in women with suspected myocardial ischemia and no obstructive coronary disease: results from the NHLBI-sponsored WISE (Women's Ischemia Syndrome Evaluation) study.

OBJECTIVES The purpose of this study was to assess the prognostic value of global magnetic resonance (MR) myocardial perfusion imaging (MPI) in women with suspected myocardial ischemia and no obstructive (stenosis <50%) coronary artery disease (CAD). BACKGROUND The prognostic value of global MR-MPI in women without obstructive CAD remains unknown. METHODS Women (n = 100, mean age 57 ± 11 years, age range 31 to 76 years), with symptoms of myocardial ischemia and with no obstructive CAD, as assessed by coronary angiography, underwent MR-MPI and standard functional assessment. During follow-up (34 ± 16 months), time to first adverse event (death, myocardial infarction, or hospitalization for worsening anginal symptoms) was analyzed using global MPI and left ventricular ejection fraction (EF) data. RESULTS Adverse events occurred in 23 (23%) women. Using univariable Cox proportional hazards regression modeling, variables found to be predictive of adverse events were global MR-MPI average uptake slope (p < 0.05), the ratio of MR-MPI peak signal amplitude to uptake slope (p < 0.05), and EF (p < 0.05). Two multivariable Cox models were formed, 1 using variables that were performance site dependent: ratio of MR-MPI peak amplitude to uptake slope together with EF (chi square: 13, p < 0.005); and a model using variables that were performance site independent: MR-MPI slope and EF (chi square: 12, p < 0.005). Each of the 2 multivariable models remained predictive of adverse events after adjustment for age, disease history, and Framingham risk score. For each of the Cox models, patients were categorized as high risk if they were in the upper quartile of the model and as not high risk otherwise. Kaplan-Meier analysis of time to event was performed for high risk versus not high risk for site-dependent (log rank: 15.2, p < 0.001) and site-independent (log rank: 13.0, p < 001) models. CONCLUSIONS Among women with suspected myocardial ischemia and no obstructive CAD, MR-MPI-determined global measurements of normalized uptake slope and peak signal uptake, together with global functional assessment of EF, appear to predict prognosis.

Physiologic compensation is supranormal in compensated aortic stenosis: does it return to normal after aortic valve replacement or is it blunted by coexistent coronary artery disease? An intramyocardial magnetic resonance imaging study.

BACKGROUND In compensated aortic stenosis (AS), cardiac performance measured at the ventricular chamber is typically supranormal, whereas measurements at the myocardium are often impaired. We investigated intramyocardial mechanics after aortic valve replacement (AVR) and the effects relative to the presence or absence of coronary artery disease (CAD+ or CAD-), respectively. METHODS AND RESULTS Twenty-nine patients (46 to 91 years, 10 female) with late but not decompensated AS underwent cardiovascular MRI before AVR (PRE), with follow-up at 6+/-1 (EARLY) and 13+/-2 months (LATE) to determine radiofrequency tissue-tagged left ventricle (LV) transmural circumferential strain, torsion, structure, and function. At the myocardial level, concentric LV hypertrophy regressed 18% LATE (93+/-22 versus 77+/-17 g/m2; P<0.0001), whereas at the LV chamber level, ejection fraction was supranormal PRE, 67+/-6% (ranging as high as 83%) decreasing to 59+/-6% LATE (P<0.05), representing not dysfunction but a return to more normal LV physiology. Between the CAD+ and CAD- groups, intramyocardial strain was similar PRE (19+/-10 versus 20+/-10) but different LATE, with dichotomization specifically related to the CAD state. In the CAD- patients, strain increased to 23+/-10% (+20%), whereas in CAD+ patients it fell to 16+/-11% (-26%), representing a nearly 50% decline after AVR (P<0.05). This was particularly evident at the apex, where CAD- strain LATE improved 17%, whereas for CAD+ it decreased 2.5-fold. Transmural strain and myocardial torsion followed a similar pattern, critically dependent on CAD. AVR impacted LV geometry and mitral apparatus, resulting in decreased mitral regurgitation, negating the double valve consideration. CONCLUSIONS In AS patients after AVR, reverse remodeling of the supranormal systolic function parallels improvement in cardiovascular MRI-derived regression of LV hypertrophy and LV intramyocardial strain. However, discordant effects are evident after AVR, driven by CAD status, suggesting that the typical AVR benefits are experienced disproportionately by those without CAD and not by those obliged to undergo concomitant coronary artery bypass grafting/AVR.

Contrast-enhanced CMR is equally effective as TEE in the evaluation of left atrial appendage thrombus in patients with atrial fibrillation undergoing pulmonary vein isolation procedure

BACKGROUND Patients with atrial fibrillation (AF) routinely undergo transesophageal echocardiography (TEE) for the evaluation of the left atrial appendage (LAA) to rule out thrombus prior to undergoing pulmonary vein isolation (PVI). Cardiac magnetic resonance (CMR) is now increasingly used for the evaluation of patients with AF to define pulmonary vein (PV) anatomy prior to PVI. OBJECTIVE To hypothesize that a retrospective comparison of 2-dimensional/3-dimensional (2D/3D) contrast-enhanced CMR sequences with TEE for the evaluation of LAA thrombus in patients with AF selected for PVI will demonstrate equivalence. METHODS Ninety-seven (N = 97) consecutive patients with AF underwent near-simultaneous TEE and noncontrast and contrast CMR prior to undergoing an initial PVI procedure. The CMR images were analyzed in 2 categories: (1) the 2D noncontrast cine images and early gadolinium enhancement images showing LAA and (2) 3D contrast source images acquired during PV magnetic resonance angiography. CMR variables evaluated were the presence or absence of LAA thrombus and the quality of images, and they were compared with the results of TEE in a blinded fashion. RESULTS All subjects were analyzed for the presence or absence of LAA thrombus. Thrombus was absent in 98% of the patients on both TEE and CMR and present in 2% on both studies (100% correlation). In 6 subjects, 2D cine CMR images were indeterminate whereas all 2D early gadolinium enhancement images and 3D contrast images were successful in excluding LAA thrombus. There was 100% concordance between CMR and TEE for the final diagnosis of LAA thrombus. CONCLUSIONS In one single examination, CMR offers a comparable alternative to TEE for the complete noninvasive evaluation of LAA thrombus and PV anatomy in patients with AF referred for PVI without obligate need for TEE.

Marked Regional Left Ventricular Heterogeneity in Hypertensive Left Ventricular Hypertrophy Patients A Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) Cardiovascular Magnetic Resonance and Echocardiographic Substudy

Concentric hypertensive left ventricular (LV) hypertrophy is presumed to be a symmetrical process. Using MRI-derived intramyocardial strain, we sought to determine whether segmental deformation was also symmetrical, as suggested by echocardiography. High echocardiographic LV relative wall thickness in hypertensive LV hypertrophy allows preserved endocardial excursion despite depressed LV midwall shortening (MWS). Depressed MWS is an adverse prognostic indicator, but whether this is related to global or regional myocardial depression is unknown. We prospectively compared MWS derived from linear echocardiographic dimensions with MR strain(∈) in septal and posterior locations in 27 subjects with ECG LV hypertrophy in the Losartan Intervention for Endpoint Reduction in Hypertension Study. Although MRI-derived mass was higher in patients than in normal control subjects (124.0±38.6 versus 60.5±13.2g/m2; P<0.001), fractional shortening (30±5% versus 33±3%) and end-systolic stress (175±22 versus 146±28 g/cm2) did not differ between groups. However, mean MR(∈) was decreased in patients versus normal control subjects (13.9±6.8% versus 22.4±3.5%), as was echo MWS (13.4±2.8% versus 18.2±1.4%; both P<0.001). For patients versus normal control subjects, posterior wall(∈) was not different (17.8±7.1% versus 21.6±4.0%), whereas septal(∈) was markedly depressed (10.1±6.6% versus 23.2±3.4%; P<0.001). Although global MWS by echocardiography or MRI is depressed in hypertensive LV hypertrophy, MRI tissue tagging demonstrates substantial regional intramyocardial strain(∈) heterogeneity, with most severely depressed strain patterns in the septum. Although posterior wall 2D principal strain was inversely related to radius of curvature, septal strain was not, suggesting that factors other than afterload are responsible for pronounced myocardial strain heterogeneity in concentric hypertrophy.

Expanding Role of Cardiovascular Magnetic Resonance in Left and Right Ventricular Diastolic Function

This article focuses on the role of cardiovascular magnetic resonance (CMR) in understanding the physiology of diastolic function and on the future applications of CMR as they relate to diastolic function evaluation. CMR has a demonstrated potential to define diastolic function and quantify its properties, in terms of active and passive stages, and its relaxation and compliance characteristics. CMR is also useful for assessing inflow and myocardial velocities, and untwisting properties of the chamber and myocardium, thus providing insights not fully available in other invasive and noninvasive strategies. CMR, which offers the necessary capabilities to evaluate the complex structure of the right ventricle, can serve in the future as the standard for evaluating diastolic function as it currently does for systolic function.

Effect of a Flexible Ventricular Restraint Device on Cardiac Remodeling after Acute Myocardial Infarction

The effects of a flexible ventricular restraint device on left ventricular (LV) dilatation and hypertrophy after transmural infarction are examined in an ovine model. Left ventricular remodeling and dilatation occurs after extensive myocardial infarction. A flexible ventricular restraint made from a nitinol mesh was evaluated in adult female sheep (n = 14). Cardiac magnetic resonance imaging scans and hemodynamic measurements were completed before and 6 weeks after anterior myocardial infarction. Treatment animals (n = 7) received passive ventricular restraint concurrently with LV infarction; the others (n = 7) served as controls. Increases in LV end-diastolic volume index were significantly less in the restraint group than in controls (0.20 ± 0.41 vs 0.83 ± 0.50 ml/kg, p < 0.03). End-systolic volumes increased less in treatment animals (0.43 ± 0.28 vs 0.90 ± 0.38 ml/kg, p < 0.03). Control hearts showed an increase in LV mass after infraction, whereas LV mass decreased in restrained hearts (0.14 ± 0.19 vs −0.25 ± 0.36 g/kg, p < 0.03). Hemodynamic studies showed similar changes after infarction for the control and the device group. Gross and microscopic examination showed no device-induced epicardial injury. A flexible ventricular restraint device attenuated remodeling after acute myocardial infarction in sheep.