Search

The goal of this study was to test whether ischemia-mediated contractile dysfunction underlying the mitral valve affects functional mitral regurgitation (FMR) and the prognostic impact of FMR.FMR results from left ventricular (LV) remodeling, which can stem from myocardial tissue alterations. Stress cardiac magnetic resonance can assess ischemia and infarction in the left ventricle and papillary muscles; relative impact on FMR is uncertain.Vasodilator stress cardiac magnetic resonance was performed in patients with known or suspected coronary artery disease at 7 sites. Images were centrally analyzed for MR etiology/severity, mitral apparatus remodeling, and papillary ischemia.A total of 8,631 patients (mean age 60.0 ± 14.1 years; 55% male) were studied. FMR was present in 27%, among whom 16% (n = 372) had advanced (moderate or severe) FMR. Patients with ischemia localized to subpapillary regions were more likely to have advanced FMR (p = 0.003); those with ischemia localized to other areas were not (p = 0.17). Ischemic/dysfunctional subpapillary myocardium (odds ratio: 1.24/10% subpapillary myocardium; confidence interval: 1.17 to 1.31; p 0.001) was associated with advanced FMR controlling for infarction. Among a subgroup with (n = 372) and without (n = 744) advanced FMR matched (1:2) on infarct size/distribution, patients with advanced FMR had increased adverse mitral apparatus remodeling, paralleled by greater ischemic/dysfunctional subpapillary myocardium (p 0.001). Although posteromedial papillary ischemia was more common with advanced FMR (p = 0.006), subpapillary ischemia with dysfunction remained associated (p 0.001), adjusting for posteromedial papillary ischemia (p = 0.074). During follow-up (median 5.1 years), 1,473 deaths occurred in the overall cohort; advanced FMR conferred increased mortality risk (hazard ratio: 1.52; 95% confidence interval: 1.25 to 1.86; p 0.001) controlling for left ventricular ejection fraction, infarction, and ischemia.Ischemic and dysfunctional subpapillary myocardium provides a substrate for FMR, which predicts mortality independent of key mechanistic substrates.

Cardiac motion and aortic pulsatility can affect the image quality of 3D contrast-enhanced MR angiography (CE-MRA). The addition of ECG gating improves image quality; however, no studies have directly linked image quality improvements to clinically used measures. In this study, we directly compared diameter measurements in the same patient from ECG-gated to non-gated CE-MRA to evaluate the impact of ECG gating upon measurement reproducibility. Fifty-three patients, referred for thoracic aortic angiography, were enrolled and underwent both non-gated and ECG-gated CE-MRA. Two readers independently measured vessel diameter, image quality, and vessel sharpness at the sinus of Valsalva (SOV), sinotubular junction (STJX), ascending aorta (AAO), distal aortic arch (DLSA), and descending aorta (DAO). Measurement reliability and reproducibility were compared between methods. Image quality with ECG gating was rated significantly higher at the SOV (3.2 ± 0.9 vs 1.2 ± 1.0, p < 0.0001), STJX (3.4 ± 0.7 vs 1.8 ± 1.0, p < 0.0001), AAO (3.5 ± 0.6 vs 1.7 ± 1.1 p < 0.0001), DLSA (4.0 ± 0.1 vs 3.6 ± 0.7, p = 0.006), and DAO (4.0 ± 0.1 vs 3.4 ± 0.9 p < 0.0001) than for non-gated studies. Bland-Altman analyses demonstrated that inter- and intra-observer variability was significantly smaller for ECG-gated MRA at the SOV and AAO. For the non-gated images at the SOV, the 95% limits of agreement for both inter- and intra-observer variability exceeded the growth-rate cutoff for surgical repair (0.5 cm). At the DAO, variability was similar between the two techniques. ECG-gated CE-MRA resulted in improved reproducibility in aortic root and ascending aortic measurements. These data suggest that ECG-gated CE-MRA should be used for the serial assessment of the ascending thoracic aorta. • ECG-gated CE-MRA improves the reproducibility and repeatability of measurements of the ascending aorta. • With non-gated CE-MRA, pulsatile motion in the proximal aorta results in significant variability in measurement reproducibility.

Aims Cardiovascular magnetic resonance (CMR) imaging is a key diagnostic tool for the evaluation of patients with suspected cardiac tumours. Patient management is guided by the CMR diagnosis, including no further testing if a mass is excluded or if only a pseudomass is found. However, there are no outcomes studies validating this approach. Methods and results In this multicentre study of patients undergoing clinical CMR for suspected cardiac tumour, CMR diagnoses were assigned as no mass, pseudomass, thrombus, benign tumour, or malignant tumour. A final diagnosis was determined after follow-up using all available data. The primary endpoint was all-cause mortality. Among 903 patients, the CMR diagnosis was no mass in 25%, pseudomass in 16%, thrombus in 16%, benign tumour in 17%, and malignant tumour in 23%. Over a median of 4.9 years, 376 patients died. Compared with the final diagnosis, the CMR diagnosis was accurate in 98.4% of patients. Patients with CMR diagnoses of pseudomass and benign tumour had similar mortality to those with no mass, whereas those with malignant tumour [hazard ratio (HR) 3.31 (2.40–4.57)] and thrombus [HR 1.46 (1.00–2.11)] had greater mortality. The CMR diagnosis provided incremental prognostic value over clinical factors including left ventricular ejection fraction, coronary artery disease, and history of extracardiac malignancy (P Conclusion In patients with suspected cardiac tumour, CMR has high diagnostic accuracy. Patients with CMR diagnoses of no mass, pseudomass, and benign tumour have similar long-term mortality. The CMR diagnosis is a powerful independent predictor of mortality incremental to clinical risk factors.

Importance Vaccine-associated myocarditis is an unusual entity that has been described for the smallpox vaccine, but only anecdotal case reports have been described for other vaccines. Whether COVID-19 vaccination may be linked to the occurrence of myocarditis is unknown. Objective To describe a group of 7 patients with acute myocarditis over 3 months, 4 of whom had recent messenger RNA (mRNA) COVID-19 vaccination. Design, Setting, and Participants All patients referred for cardiovascular magnetic resonance imaging at Duke University Medical Center were asked to participate in a prospective outcomes registry. Two searches of the registry database were performed: first, to identify patients with acute myocarditis for the 3-month period between February 1 and April 30 for 2017 through 2021, and second, to identify all patients with possible vaccine-associated myocarditis for the past 20 years. Once patients with possible vaccine-associated myocarditis were identified, data available in the registry were supplemented by additional data collection from the electronic health record and a telephone interview. Exposures mRNA COVID-19 vaccine. Main Outcomes and Measures Occurrence of acute myocarditis by cardiovascular magnetic resonance imaging. Results In the 3-month period between February 1 and April 30, 2021, 7 patients with acute myocarditis were identified, of which 4 occurred within 5 days of COVID-19 vaccination. Three were younger male individuals (age, 23-36 years) and 1 was a 70-year-old female individual. All 4 had received the second dose of an mRNA vaccine (2 received mRNA-1273 [Moderna], and 2 received BNT162b2 [Pfizer]). All presented with severe chest pain, had biomarker evidence of myocardial injury, and were hospitalized. Coincident testing for COVID-19 and respiratory viruses provided no alternative explanation. Cardiac magnetic resonance imaging findings were typical for myocarditis, including regional dysfunction, late gadolinium enhancement, and elevated native T1 and T2. Conclusions and Relevance In this study, magnetic resonance imaging findings were found to be consistent with acute myocarditis in 7 patients; 4 of whom had preceding COVID-19 vaccination. Further investigation is needed to determine associations of COVID-19 vaccination and myocarditis.

OBJECTIVE To determine the prevalence and prognostic significance of unrecognized myocardial infarction (MI) by delayed-enhancement MRI (DE-MRI) in asymptomatic patients with diabetes. RESEARCH DESIGN AND METHODS In this prospective, two-center study of asymptomatic patients without known cardiac disease (n = 120), two prespecified cohorts underwent a research MRI: 1) a high-risk group with type 1 diabetes and chronic renal insufficiency (n = 50) and 2) an average-risk group with type 2 diabetes (n = 70). The primary end point was a composite of all-cause mortality and clinical MI. RESULTS Overall, the prevalence of unrecognized MI was 19% by DE-MRI (28% high-risk group and 13% average-risk group) and 5% by electrocardiography. During up to 5 years of follow-up with a total of 460 patient-years of follow-up, the rate of death/MI was markedly higher in patients with diabetes with (vs. without) unrecognized MI (all 44% vs. 7%, high-risk group 43% vs. 6%, and average-risk group 44% vs. 8%; all P < 0.01). After adjustment for Framingham risk score, left ventricular ejection fraction, and diabetes type, the presence of unrecognized MI by DE-MRI conferred an eightfold increase in risk of death/MI (95% CI 3.0–21.1, P < 0.0001). Addition of unrecognized MI to clinical indices significantly improved model discrimination for adverse events (integrated discrimination improvement = 0.156, P = 0.001). CONCLUSIONS Unrecognized MI is prevalent in asymptomatic patients with diabetes without a history of cardiac disease and confers a markedly increased risk of death and clinical MI.

Background: Microvascular obstruction (MO) is a pathophysiologic complication of acute myocardial infarction that portends poor prognosis; however, it is transient and disappears with infarct healing. Much remains unknown regarding its pathophysiology and whether there are predictors of MO that could function as stable surrogates. We tested for clinical and cardiovascular magnetic resonance predictors of MO to gain insight into its pathophysiology and to find a stable surrogate. Methods: Three hundred two consecutive patients from 2 centers underwent cardiovascular magnetic resonance within 2 weeks of first acute myocardial infarction. Three measures of infarct morphology: infarct size, transmurality, and a new index—the epicardial surface area (EpiSA) of full-thickness infarction—were quantified on delayed-enhancement cardiovascular magnetic resonance. Results: Considering all clinical characteristics, only measures of infarct morphology were independent predictors of MO. EpiSA was the strongest predictor of MO and provided incremental predictive value beyond that of infarct size and transmurality ( P P =0.045). Conclusions: The EpiSA of infarction is a novel index of infarct morphology which accurately predicts MO during the first 2 weeks of MI, but unlike MO, does not disappear with infarct healing. This index has potential as a stable surrogate of the presence of acute MO and may be useful as a predictor of adverse remodeling and outcome which is less dependent on the time window of patient assessment.

Recently developed dark-blood techniques such as Flow-Independent Dark-blood DeLayed Enhancement (FIDDLE) allow simultaneous visualization of tissue contrast-enhancement and blood-pool suppression. Critical to FIDDLE is the magnetization preparation, which accentuates differences between myocardium and blood-pool. Here, we compared magnetization transfer (MT)-preparation and T2-preparation for use with FIDDLE. Variants of FIDDLE were developed with MT- or T2-preparation modules and tested in 35 patients (11 at 1.5 T, 24 at 3 T). Images were acquired with each FIDDLE variant in an interleaved fashion 10 minutes after gadolinium administration with otherwise identical acquisition parameters. Images were visually and quantitatively assessed for artifacts and differences in right ventricle to left ventricle (RV-to-LV) blood-pool suppression. Bright artifacts, reflecting incomplete blood-pool suppression, were frequently observed in the left atrium with T2-preparation FIDDLE at 1.5 and 3 T (82% and up to 100% of patients, respectively). MT-preparation FIDDLE resulted in fewer patients with artifacts (0% at 1.5 T, 22% at 3 T; P < .01). Left atrial blood-pool signal was significantly more homogeneous with MT-preparation than with T2-preparation at 1.5 and 3 T (P < .001 for all comparisons). Visibly different RV-to-LV blood-pool suppression was observed with T2-preparation in 36% of patients at 1.5 T and up to 94% at 3 T. In these patients, RV blood-pool signal was elevated, reducing the conspicuity of the myocardial-RV blood-pool border. Conversely, there were no visible differences in RV-to-LV blood-pool suppression with MT-preparation. Quantitative assessment of differences in blood-pool suppression and blood-pool artifacts was consistent with visual analyses. We conclude that for dark blood-blood delayed-enhancement imaging of the heart, MT-preparation results in fewer bright blood-pool artifacts and more uniform blood-pool suppression than T2-preparation.

Purpose We demonstrate an improved segmented inversion-recovery sequence that suppresses ghost artifacts arising from tissues with long T1 ( > 1.5 s). Theory and Methods Long T1 species such as pericardial fluid can create bright ghost artifacts in segmented, inversion-recovery MRI because of oscillations in longitudinal magnetization between segments. A single dummy acquisition at the beginning of the sequence can reduce oscillations; however, its effectiveness in suppressing long T1 artifacts is unknown. In this study, we systematically evaluated several test sequences, including a prototype (saturation post-pulse readout to eliminate spurious signal: SPPRESS) in simulations, phantoms, and patients. Results SPPRESS reduced artifact signal 90% ± 25% and 74% ± 28% compared with Control and Single-Dummy methods in phantoms. SPPRESS performed well at 1.5 Tesla (T) and 3T, with steady-state free precession (SSFP) and fast low-angle shot (FLASH) readout, with conventional and phase-sensitive reconstruction, and over a range of physiologic heart rates. A review of 100 consecutive clinical cardiac MRI scans revealed large fluid collections (eg, regions with long T1) in 14% of patients. In a prospectively enrolled cohort of 16 patients with visible long T1 fluids, SPPRESS appreciably reduced artifacts in all cases compared with Control and Single-Dummy methods. Conclusion We developed and validated a new robust method, SPPRESS, for reducing artifacts due to long T1 species across a wide range of imaging and physiologic conditions. Magn Reson Med, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

Stress cardiac magnetic resonance imaging (CMR) is not widely used in current clinical practice, and its ability to predict patient mortality is unknown.To determine whether stress CMR is associated with patient mortality.Real-world evidence from consecutive clinically ordered CMR examinations. Multicenter study of patients undergoing clinical evaluation of myocardial ischemia. Patients with known or suspected coronary artery disease (CAD) underwent clinical vasodilator stress CMR at 7 different hospitals. An automated process collected data from the finalized clinical reports, deidentified and aggregated the data, and assessed mortality using the US Social Security Death Index.All-cause patient mortality.Of the 9151 patients, the median (interquartile range) patient age was 63 (51-70) years, 55% were men, and the median (interquartile range) body mass index was 29 (25-33) (calculated as weight in kilograms divided by height in meters squared). The multicenter automated process yielded 9151 consecutive patients undergoing stress CMR, with 48 615 patient-years of follow-up. Of these patients, 4408 had a normal stress CMR examination, 4743 had an abnormal examination, and 1517 died during a median follow-up time of 5.0 years. Using multivariable analysis, addition of stress CMR improved prediction of mortality in 2 different risk models (model 1 hazard ratio [HR], 1.83; 95% CI, 1.63-2.06; P .001; model 2: HR, 1.80; 95% CI, 1.60-2.03; P .001) and also improved risk reclassification (net improvement: 11.4%; 95% CI, 7.3-13.6; P .001). After adjustment for patient age, sex, and cardiac risk factors, Kaplan-Meier survival analysis showed a strong association between an abnormal stress CMR and mortality in all patients (HR, 1.883; 95% CI, 1.680-2.112; P .001), patients with (HR, 1.955; 95% CI, 1.712-2.233; P .001) and without (HR, 1.578; 95% CI, 1.235-2.2018; P .001) a history of CAD, and patients with normal (HR, 1.385; 95% CI, 1.194-1.606; P .001) and abnormal left ventricular ejection fraction (HR, 1.836; 95% CI, 1.299-2.594; P .001).Clinical vasodilator stress CMR is associated with patient mortality in a large, diverse population of patients with known or suspected CAD as well as in multiple subpopulations defined by history of CAD and left ventricular ejection fraction. These findings provide a foundational motivation to study the comparative effectiveness of stress CMR against other modalities.

This study introduced and validated a novel flow-independent delayed enhancement technique that shows hyperenhanced myocardium while simultaneously suppressing blood-pool signal.The diagnosis and assessment of myocardial infarction (MI) is crucial in determining clinical management and prognosis. Although delayed enhancement cardiac magnetic resonance (DE-CMR) is an in vivo reference standard for imaging MI, an important limitation is poor delineation between hyperenhanced myocardium and bright LV cavity blood-pool, which may cause many infarcts to become invisible.A canine model with pathology as the reference standard was used for validation (n = 22). Patients with MI and normal controls were studied to ascertain clinical performance (n = 31).In canines, the flow-independent dark-blood delayed enhancement (FIDDLE) technique was superior to conventional DE-CMR for the detection of MI, with higher sensitivity (96% vs. 85%, respectively; p = 0.002) and accuracy (95% vs. 87%, respectively; p = 0.01) and with similar specificity (92% vs, 92%, respectively; p = 1.0). In infarcts that were identified by both techniques, the entire length of the endocardial border between infarcted myocardium and adjacent blood-pool was visualized in 33% for DE-CMR compared with 100% for FIDDLE. There was better agreement for FIDDLE-measured infarct size than for DE-CMR infarct size (95% limits-of-agreement, 2.1% vs. 5.5%, respectively; p 0.0001). In patients, findings were similar. FIDDLE demonstrated higher accuracy for diagnosis of MI than DE-CMR (100% [95% confidence interval [CI]: 89% to 100%] vs. 84% [95% CI: 66% to 95%], respectively; p = 0.03).The study introduced and validated a novel CMR technique that improves the discrimination of the border between infarcted myocardium and adjacent blood-pool. This dark-blood technique provides diagnostic performance that is superior to that of the current in vivo reference standard for the imaging diagnosis of MI.

Supplemental Digital Content is available in the text., Rationale: After acute myocardial infarction (MI), delineating the area-at-risk (AAR) is crucial for measuring how much, if any, ischemic myocardium has been salvaged. T2-weighted MRI is promoted as an excellent method to delineate the AAR. However, the evidence supporting the validity of this method to measure the AAR is indirect, and it has never been validated with direct anatomic measurements. Objective: To determine whether T2-weighted MRI delineates the AAR. Methods and Results: Twenty-one canines and 24 patients with acute MI were studied. We compared bright-blood and black-blood T2-weighted MRI with images of the AAR and MI by histopathology in canines and with MI by in vivo delayed-enhancement MRI in canines and patients. Abnormal regions on MRI and pathology were compared by (a) quantitative measurement of the transmural-extent of the abnormality and (b) picture matching of contours. We found no relationship between the transmural-extent of T2-hyperintense regions and that of the AAR (bright-blood-T2: r=0.06, P=0.69; black-blood-T2: r=0.01, P=0.97). Instead, there was a strong correlation with that of infarction (bright-blood-T2: r=0.94, P

Background Acute myocardial infarct (AMI) size depicted by late gadolinium enhancement cardiovascular magnetic resonance (CMR) is increasingly used as an efficacy endpoint in randomized trials comparing AMI therapies. Infarct size is quantified using manual planimetry (MANUAL), visual scoring (VISUAL), or automated techniques using signal-intensity thresholding (AUTO). Although AUTO is considered the most reproducible, prior studies did not account for the subjective determination of endocardial/epicardial borders, which all methods require. For MANUAL and VISUAL, prior studies did not address how to treat intermediate signal intensities due to partial volume. Methods To assess sources of variability, AMI size was measured in 30 patients and 12 controls by 3 core-laboratories using 8 methods, each separated by more than 2 months time (n = 720 evaluations). The methods were: (1,2) AUTOSegment, AUTOFWHM (using Segment software or the full-width-at-half-maximum algorithm, respectively); (3,4) AUTO-UCSegment, AUTO-UCFWHM (user correction for endocardial border pixels, no-reflow, etc.); (5) MANUAL; (6) MANUAL-ISI (adjustment for intermediate signal-intensities); (7) VISUAL; (8) VISUAL-ISI. Results Mean infarct size varied between 16.8% and 27.2% of LV mass depending on method. Even automated techniques with no user interaction for infarct borders resulted in significant within-patient variability given the need to subjectively trace endocardial/epicardial contours. The coefficient-of-variation (CV) was 10.6% and 14.6% for AUTOSegment and AUTOFWHM, respectively. For manual and visual categories, reproducibility was improved when intermediate signal-intensities were considered (MANUAL-ISI vs MANUAL: CV = 8.3% vs 14.4%; p = 0.03; VISUAL-ISI vs VISUAL: CV = 8.4% vs 10.9%; p = 0.01). For AUTO-UCSegment, MANUAL-ISI, and VISUAL-ISI (best technique in each category) within-patient variability due to the quantification method was less than 10% of total variability, and the required sample sizes for detecting a 5% absolute difference in infarct size were 62, 63, and 62 patients, respectively. Conclusion Among CMR core-laboratories, an important source of variability in infarct size quantification is the subjective delineation of endocardial/epicardial borders. When intermediate signal intensities are considered in manual planimetry and visual scoring, reproducibility and impact on sample size are similar to automated techniques.

To compare the utility and efficacy of stress cardiac magnetic resonance (MR) imaging and stress echocardiography in an emergency setting in patients with acute chest pain (CP) and intermediate risk of coronary artery disease (CAD).Written informed consent was obtained from all patients. This HIPAA-compliant study was approved by the institutional review board for research ethics. Sixty patients without history of CAD presented to the emergency department with intermediate-risk acute CP and were prospectively enrolled. Patients underwent both stress cardiac MR imaging and stress echocardiography in random order within 12 hours of presentation. Stress imaging results were interpreted clinically immediately (blinded interpretation was performed months later), and coronary angiography was performed if either result was abnormal. CAD was considered significant if it was identified at angiography (narrowing50% ) or if a cardiac event (death or myocardial infarction) occurred during follow-up (mean, 14 months ± 5 [standard deviation]). McNemar test was used to compare the diagnostic accuracy of techniques.Stress cardiac MR imaging and stress echocardiography had similar specificity, accuracy, and positive and negative predictive values (92% vs 96%, 93% vs 88%, 67% vs 60%, and 100% vs 91%, respectively, for clinical interpretation; 90% vs 92%, 90% vs 88%, 58% vs 56%, and 98% vs 94%, respectively, for blinded interpretation). Stress cardiac MR imaging had higher sensitivity at clinical interpretation (100% vs 38%, P = .025), which did not reach significance at blinded interpretation (88% vs 63%, P = .31). However, multivariable logistic regression analysis showed stress cardiac MR imaging to be the strongest independent predictor of significant CAD (P = .002).In patients presenting to the emergency department with intermediate-risk CP, adenosine stress cardiac MR imaging performed within 12 hours of presentation is safe and potentially has improved performance characteristics compared with stress echocardiography. Online supplemental material is available for this article.

ObjectivesThis study tested the diagnostic and prognostic utility of a rapid, visual T1 assessment method for identification of cardiac amyloidosis (CA) in a “real-life” referral population undergoing cardiac magnetic resonance for suspected CA.BackgroundIn patients with confirmed CA, delayed-enhancement cardiac magnetic resonance (DE-CMR) frequently shows a diffuse, global hyperenhancement (HE) pattern. However, imaging is often technically challenging, and the prognostic significance of diffuse HE is unclear.MethodsNinety consecutive patients referred for suspected CA and 64 hypertensive patients with left ventricular hypertrophy (LVH) were prospectively enrolled and underwent a modified DE-CMR protocol. After gadolinium administration a method for rapid, visual T1 assessment was used to identify the presence of diffuse HE during the scan, allowing immediate optimization of settings for the conventional DE-CMR that followed. The primary endpoint was all-cause mortality.ResultsAmong patients with suspected CA, 66% (59 of 90) demonstrated HE, with 81% (48 of 59) of these meeting pre-specified visual T1 assessment criteria for diffuse HE. Among hypertensive LVH patients, 6% (4 of 64) had HE, with none having diffuse HE. During 29 months of follow-up (interquartile range: 12 to 44 months), there were 50 (56%) deaths in patients with suspected CA and 4 (6%) in patients with hypertensive LVH. Multivariable analysis demonstrated that the presence of diffuse HE was the most important predictor of death in the group with suspected CA (hazard ratio: 5.5, 95% confidence interval: 2.7 to 11.0; p < 0.0001) and in the population as a whole (hazard ratio: 6.0, 95% confidence interval 3.0 to 12.1; p < 0.0001). Among 25 patients with myocardial histology obtained during follow-up, the sensitivity, specificity, and accuracy of diffuse HE in the diagnosis of CA were 93%, 70%, and 84%, respectively.ConclusionsAmong patients suspected of CA, the presence of diffuse HE by visual T1 assessment accurately identifies patients with histologically-proven CA and is a strong predictor of mortality.

Introduction: The purpose of this study was to assess velocity-encoded cardiac magnetic resonance imaging (Ve-CMR) in a population of patients referred for cardiac magnetic resonance imaging (CMR), to determine the variability of atrial function, and to identify clinical parameters associated with left atrial function. Methods: This is a prospective study evaluating patients who were referred to our CMR center for a clinical CMR. Left atrial function was obtained via Ve-CMR thru-plane images across the mitral valve after acquiring 2 perpendicular in-plane images as “scouts”. The atrial function and mitral inflow were quantified by computer analysis (Argus, Siemens). Atrial function was defined as atrial contraction (A-wave) volume divided by total inflow volume. Left atrial volumes were calculated via computer analysis. Mitral regurgitation and left ventricular ejection fractions were assessed visually. Results: Thirty-nine patients, with mean age 56 +/- 10 years, were enrolled. The mean left atrial function was 22.9% +/-14.5%; the range in left atrial function was 0% - 57%. There was a significant positive correlation between atrial function and increased left ventricular ejection fraction (r = 0.44, P

Background A fundamental component of the CMR exam is contrast enhanced imaging, which is crucial for delineating diseased from normal tissue. Unfortunately, diseased tissue adjacent to vasculature often remains hidden since there is poor contrast between hyperenhanced tissue and bright blood-pool. Conventional black-blood double-IR methods are not a solution; these were not designed to function after contrast administration since they rely on the long native T1 of blood (~2s at 3T) and adequate blood flow within this time period. We introduce a novel Flow-Independent Dark-blood DeLayed Enhancement technique (FIDDLE) that allows visualization of tissue contrast-enhancement while suppressing blood-pool signal. We validate FIDDLE in an animal model of myocardial infarction (MI) and demonstrate feasibility in patients.

Objectives This study sought to evaluate performance characteristics of routine echo for left ventricular thrombus (LVT). Background Although the utility of dedicated echocardiography (echo) for LVT is established, echo is widely used as a general test for which LVT is rarely the primary indication. We used delayed-enhancement cardiac magnetic resonance (DE-CMR) as a reference to evaluate LVT detection by routine echo. Methods Dedicated LVT assessment using DE-CMR was prospectively performed in patients with left ventricular systolic dysfunction. Echoes were done as part of routine clinical care. Echo and CMR were independently read for LVT and related indexes of LVT size, shape, and image quality/diagnostic confidence. Follow-up was done for embolic events and pathology validation of LVT. Results In this study, 243 patients had routine clinical echo and dedicated CMR within 1 week without intervening events. Follow-up supported DE-CMR as a reference standard, with >5-fold difference in endpoints between patients with versus without LVT by DE-CMR (p = 0.02). LVT prevalence was 10% by DE-CMR. Echo contrast was used in 4% of patients. Echo sensitivity and specificity were 33% and 91%, with positive and negative predictive values of 29% and 93%. Among patients with possible LVT as the clinical indication for echo, sensitivity and positive predictive value were markedly higher (60%, 75%). Regarding sensitivity, echo performance related to LVT morphology and mirrored cine-CMR, with protuberant thrombus typically missed when small (p ≤ 0.02). There was also a strong trend to miss mural thrombus irrespective of size (p = 0.06). Concerning positive predictive value, echo performance related to image quality, with lower diagnostic confidence scores for echoes read positive for LVT in discordance with DE-CMR compared with echoes concordant with DE-CMR (p Conclusions Routine echo with rare contrast use can yield misleading results concerning LVT. Echo performance is improved when large protuberant thrombus is present and when the clinical indication is specifically for LVT assessment.

Aim The presence of septal hypertrophy in hypertrophic cardiomyopathy (HCM) is common. To date, there has been no accepted classification of septal morphology in HCM. Furthermore, the possible relationship between septal morphology and clinical features of HCM is undefined. Methods and results Seventy-five consecutive adult patients with HCM were enrolled. Septal morphologies were retrospectively categorized into one of four patterns of hypertrophy based on transthoracic echocardiography. Left ventricular diastolic function by Doppler echocardiography and late gadolinium enhancement (LGE) by magnetic resonance imaging were assessed in all patients. Patients were followed for a mean of 45 ± 32 months. Catenoid septum was the most common morphologic subtype (46 of 75, 61%), followed by simple sigmoid (22 of 75, 29%), neutral (4 of 75, 5%), and apical (3 of 75, 4%). Inter-observer reproducibility of septal classifications was high (κ = 0.95). Patients with the catenoid subtype presented at a younger age, had worse diastolic function, and high rates of LGE. The presence of catenoid septal morphology was independently associated with LGE in multivariable logistic regression analysis. Implantable cardioverter-defibrillator implantation for prevention of sudden cardiac death occurred only in patients with this septal morphology. Conclusion We propose a simple, reproducible classification system of patterns of septal hypertrophy in HCM. These patterns of hypertrophy are associated with significant differences in clinical, haemodynamic, and myocardial characteristics. Further studies are needed to evaluate the relationship between septal morphology and outcome or response to therapies in HCM.

Inflammation has been shown to be a major component in the pathophysiology of acute coronary syndrome (ACS). In patients presenting with acute myocardial infarction (AMI), a critical component of the ACS spectrum, multiple coronary arteries are involved during this inflammatory process. In addition to the coronary vasculature, the inflammatory cascade has also been shown to affect the carotid arteries and possibly the aorta.To assess the involvement of the aorta during AMI by cardiac magnetic resonance (CMR).We prospectively evaluated the aortic wall by CMR in 123 patients. 78 patients were enrolled from the emergency department (ED), who presented with chest pain and were classified as either: (1) AMI: elevated troponin levels and typical chest pain or (2) non-cardiac chest pain (CP): negative troponins and a normal stress test or normal cardiac catheterization. We compared these 2 groups to a group of 45 asymptomatic diabetic patients. The descending thoracic aortic wall area (AWA) and maximal aortic wall thickness (AWT) were measured using a double inversion recovery T-2 weighted, ECG-gated, spin echo sequence by CMR.Patients with AMI were older, more likely to smoke, had a higher incidence of claudication, and had higher CRP levels. The AWA and maximal AWT were greater in patients who presented to the ED with ACS (2.11+/-0.17 mm(2), and 3.17+/-0.19 mm, respectively) than both patients presenting with non-cardiac CP (1.52+/-0.58 mm(2), p0.001; and 2.57+/-0.10 mm, p0.001) and the diabetic patients (1.38+/-0.58 mm(2), p0.001; and 2.30+/-0.131 mm, p0.001). The difference in the aortic wall characteristics remained significant after correcting for body mass index, hyperlipidemia, statins and C-reactive protein. There was no difference in maximal AWT or AWA between patients with non-cardiac CP and patients with diabetes.Patients with AMI have a significantly greater maximal aortic wall thickness and area compared to patients with non-cardiac CP. Longitudinal studies are needed to assess whether this increase is due to inflammation or a higher atherosclerotic burden.

ObjectivesThis study sought to compare contrast-enhanced anatomic imaging and contrast-enhanced tissue characterization (delayed-enhancement cardiac magnetic resonance [DE-CMR]) for left ventricular (LV) thrombus detection.BackgroundContrast echocardiography (echo) detects LV thrombus based on anatomic appearance, whereas DE-CMR imaging detects thrombus based on tissue characteristics. Although DE-CMR has been validated as an accurate technique for thrombus, its utility compared with contrast echo is unknown.MethodsMultimodality imaging was performed in 121 patients at high risk for thrombus due to myocardial infarction or heart failure. Imaging included 3 anatomic imaging techniques for thrombus detection (contrast echo, noncontrast echo, cine-CMR) and a reference of DE-CMR tissue characterization. LV structural parameters were quantified to identify markers for thrombus and predictors of additive utility of contrast-enhanced thrombus imaging.ResultsTwenty-four patients had thrombus by DE-CMR. Patients with thrombus had larger infarcts (by DE-CMR), more aneurysms, and lower LV ejection fraction (by CMR and echo) than those without thrombus. Contrast echo nearly doubled sensitivity (61% vs. 33%, p < 0.05) and yielded improved accuracy (92% vs. 82%, p < 0.01) versus noncontrast echo. Patients who derived incremental diagnostic utility from DE-CMR had lower LV ejection fraction versus those in whom noncontrast echo alone accurately assessed thrombus (35 ± 9% vs. 42 ± 14%, p < 0.01), with a similar trend for patients who derived incremental benefit from contrast echo (p = 0.08). Contrast echo and cine-CMR closely agreed on the diagnosis of thrombus (κ = 0.79, p < 0.001). Thrombus prevalence was lower by contrast echo than DE-CMR (p < 0.05). Thrombus detected by DE-CMR but not by contrast echo was more likely to be mural in shape or, when apical, small in volume (p < 0.05).ConclusionsEcho contrast in high-risk patients markedly improves detection of LV thrombus, but does not detect a substantial number of thrombi identified by DE-CMR tissue characterization. Thrombi detected by DE-CMR but not by contrast echo are typically mural in shape or small in volume.

Chhabra D, Grafals M, Cabral B, Leventhal J, Parker M, Gallon L. Late conversion of tacrolimus to sirolimus in a prednisone-free immunosuppression regimen in renal transplant patients. Clin Transplant 2009: DOI: 10.1111/j.1399-0012.2009.01047.x © 2009 John Wiley & Sons A/S. Abstract: Background: One of the most important causes of graft loss is chronic nephrotoxicity from calcineurin inhibitors. The aim of this study was to evaluate the feasibility and to assess the impact on rejection risk, graft loss and renal allograft function of converting patients from tacrolimus (Tac) to sirolimus (SRL) at one yr post-transplantation (Tx) using a prednisone-free immunosuppressive regimen. Methods: Two hundred fifty-five kidney transplant patients were induced with Alemtuzumab and maintained on a steroid-free regimen with Tac and mycophenolate mofetil. Thirty-seven stable patients (14%) were converted from Tac to SRL at one yr post-Tx. Results: The two groups were demographically similar. Mean post-tx follow-up was 2.8 ± 0.2 yr. Patient and graft survival were not statistically different. There was no significant difference in acute rejection episodes between the SRL and Tac groups (21% vs. 15%, p = 0.2). Calculated glomerular filtration rate (GFR), in the SRL group at 2.8 yr post-tx, was 69 ± 13 mL/min from the one month post-tx GFR of 53 ± 19 and 59 ± 23 mL/min from the one month post-tx GFR of 56 ± 21 mL/min in the Tac group. Conclusions: Using a prednisone-free regimen, the conversion of Tac to SRL at one yr post-Tx was not associated with an increased risk of acute rejection or graft loss.

Background. BK nephropathy (BKVN) is a significant cause of graft dysfunction in kidney transplant recipients, but its course in simultaneous pancreas-kidney (SPK) recipients is less well studied. The presence of dual organs limits the ability to reduce maintenance immunosuppression, typically the first intervention in the management of BKVN. Methods. A single center, retrospective review was conducted of 205 SPK transplants performed from January 1, 2000 to April 30, 2006. Results. The 5-year actuarial cumulative rate of BKVN was 5.6%. Diagnosis occurred at a median of 20 months after transplant; mean serum creatinine was 2.6, and geometric mean BK serum viral load was 709,274 copies/mL at diagnosis. There was no statistical difference in the cumulative rate according to the use of induction therapy: rabbit antilymphocyte globulin (5-year rate 6.8%, 4/59), alemtuzumab (5-year rate 5.1%, 5/146). Treatment consisted of immunosuppression reduction and half received cidofovir. Eight of nine kidney allografts eventually failed, but all patients retained pancreatic allograft function. Conclusions. BKVN occurs in 5.6% of SPK recipients. There is no difference in the cumulative rate of BKVN between patients who received alemtuzumab or rabbit antilymphocyte globulin.

Objectives This study sought to assess the prevalence and markers of left ventricular (LV) thrombus among patients with systolic dysfunction. Background Prior studies have yielded discordant findings regarding prevalence and markers of LV thrombus. Delayed-enhancement cardiovascular magnetic resonance (DE-CMR) identifies thrombus on the basis of tissue characteristics rather than just anatomical appearance and is potentially highly accurate. Methods Prevalence of thrombus by DE-CMR was determined in 784 consecutive patients with systolic dysfunction (left ventricular ejection fraction [LVEF] Results Among this at-risk population (age 60 ± 14 years; LVEF 32 ± 11%), DE-CMR detected thrombus in 7% (55 patients) and cine-CMR in 4.7% (37 patients, p Conclusions In a broad cross section of patients with systolic dysfunction, thrombus prevalence was 7% by DE-CMR and included small intracavitary and small or large mural thrombus missed by cine-CMR. Prevalence increased with worse LVEF, ischemic etiology, and increased myocardial scarring.

Background and objectives: The impact of posttransplantation anemia on patient survival, renal allograft survival, and rate of acute rejection is not known. Design, setting, participants, & measurements: A total of 1023 patients who underwent kidney transplantation at one center from January 1992 through June 2003 were retrospectively analyzed. Posttransplantation anemia was defined as mean hemoglobin

Objectives We wanted to assess the value of cardiovascular magnetic resonance (CMR) stress testing for evaluation of women with suspected coronary artery disease (CAD). Background A combined perfusion and infarction CMR examination can accurately diagnose CAD in the clinical setting in a mixed gender population. Methods We prospectively enrolled 147 consecutive women with chest pain or other symptoms suggestive of CAD at 2 centers (Duke University Medical Center, Robert-Bosch-Krankenhaus). Each patient underwent a comprehensive clinical evaluation, a CMR stress test consisting of cine rest function, adenosine-stress and rest perfusion, and delayed-enhancement CMR infarction imaging, and X-ray coronary angiography within 24 h. The components of the CMR test were analyzed visually both in isolation and combined using a pre-specified algorithm. Coronary artery disease was defined as stenosis ≥70% on quantitative analysis of coronary angiography. Results Cardiovascular magnetic resonance imaging was completed in 136 females (63.0 ± 11.1 years), 37 (27%) women had CAD on coronary angiography. The combined CMR stress test had a sensitivity, specificity, and accuracy of 84%, 88%, and 87%, respectively, for the diagnosis of CAD. Diagnostic accuracy was high at both sites (Duke University Medical Center 82%, Robert-Bosch-Krankenhaus 90%; p = 0.18). The accuracy for the detection of CAD was reduced when intermediate grade stenoses were included (82% vs. 87%; p = 0.01 compared the cutoff of stenosis ≥50% vs. ≥70%). The sensitivity was lower in women with single-vessel disease (71% vs. 100%; p = 0.06 compared with multivessel disease) and small left ventricular mass (69% vs. 95%; p = 0.04 for left ventricular mass ≤97 g vs. >97 g). The latter difference was even more significant after accounting for end-diastolic volumes (70% vs. 100%; p = 0.02 for left ventricular mass indexed to end-diastolic volume ≤1.15 g/ml vs. >1.15 g/ml). Conclusions A multicomponent CMR stress test can accurately diagnose CAD in women. Detection of CAD in women with intermediate grade stenosis, single-vessel disease, and with small hearts is challenging.

Background— Atrial septal defect (ASD) flow can be measured indirectly by velocity-encoded cardiovascular magnetic resonance (veCMR) of the pulmonary artery and aorta. Imaging the secundum ASD en face could potentially enable direct flow measurement and provide valuable information about ASD size, shape, location, and proximity to other structures. Methods and Results— Forty-four patients referred for possible transcatheter ASD closure underwent a comprehensive standard evaluation, including transesophageal and/or intracardiac echocardiography and invasive oximetry. CMR was performed in parallel and included direct en face veCMR after an optimal double-oblique imaging plane was determined that accounted for ASD flow direction and cardiac-cycle interatrial septal motion. ASD flow measured by direct en face veCMR correlated better with invasive oximetry than indirect (pulmonary artery and aorta) veCMR ( r =0.80 versus r =0.66). Additionally, 95% limits of agreement were narrower (�3.9 versus �5.1 L/min). En face veCMR determined that defects usually were eccentrically shaped (major/minor axis length >1.5) rather than circular, with 16% having extreme eccentricity (major/minor >2.0). Overall, ASD size by both veCMR and intracardiac echocardiography correlated with final device size; however, in small to medium defects (2 ) and extremely eccentric defects, veCMR correlated better with final device size than did intracardiac echocardiography. Importantly, CMR identified additional information in 9 patients (20%) that altered clinical management. Specifically, en face veCMR detected additional defects (n=3), large ASD with insufficient rim tissue (n=2), and sinus venosus defect with anomalous pulmonary vein (n=1). Cine and/or morphological imaging detected interrupted inferior vena cava (n=2) and sinus of Valsalva aneurysm (n=1). Conclusions— En face veCMR with an optimized imaging plane can determine ASD flow, size, and morphology. CMR provided information incremental to comprehensive standard evaluation that altered clinical management in 20% of patients.

Background— The identification and assessment of myocardial infarction (MI) are important for therapeutic and prognostic purposes, yet current recommended diagnostic strategies have significant limitations. We prospectively tested the performance of delayed-enhancement magnetic resonance imaging (MRI) with gadolinium-based contrast for the detection of MI in an international, multicenter trial. Methods and Results— Patients with their first MI were enrolled in an acute (≤16 days after MI; n=282) or chronic (17 days to 6 months; n=284) arm and then randomized to 1 of 4 doses of gadoversetamide: 0.05, 0.1, 0.2, or 0.3 mmol/kg. Standard delayed-enhancement MRI was performed before contrast (control) and 10 and 30 minutes after gadoversetamide. For blinded analysis, precontrast and postcontrast MRIs were randomized and then scored for enhanced regions by 3 independent readers not associated with the study. The infarct-related artery perfusion territory was scored from x-ray angiograms separately. In total, 566 scans were performed in 26 centers using commercially available scanners from all major US/European vendors. All scans were included in the analysis. The sensitivity of MRI for detecting MI increased with rising dose of gadoversetamide ( P P P Conclusions— Gadoversetamide-enhanced MRI using doses of ≥0.2 mmol/kg is effective in the detection and assessment of both acute and chronic MI. This study represents the first multicenter trial designed to evaluate an imaging approach for detecting MI.

Background It is not known how different steroid-free immunosuppressive combinations affect long-term kidney transplant function in recipients of simultaneous kidney and pancreas transplant (SPK). Here, we sought to evaluate, in SPK recipients, the impact on long-term renal allograft function of two Tac-based prednisone-free maintenance immunosuppressive protocols: tacrolimus (Tac)/mycophonelate mofetil (MMF) versus Tac/ sirolimus (SRL). Methods In this single-center, retrospective, sequential study, we analyzed 59 SPK transplant patients with at median follow up of 5 years. All patients received induction therapy with thymoglobulin and maintenance immunosuppression with Tac/MMF (n=22) or Tac/SRL (n=37). There were no differences between the two groups in regards to age, gender, race, panel reactive antibodies, degree of mismatch, donor age, incidence of delay graft function, and Tac trough levels at different time points after transplantation. Results Kaplan-Meier patient survival at 6 years after transplantation was not statistically different between the two groups. Rate of ACR was similar. Kidney survival, even if not statistically significant, was better in the Tac/MMF group than in the Tac/SRL (90.7% vs. 70.7%, P=0.09). The slope of glomerular filtration rate decline per month at 5 years after transplantation was not statistically different between the two groups. Both groups had the same decline over time in glomerular filtration rate of 0.40+/-0.06 mL/min/1.73/month. Pancreas survival at 6 years after transplantation was 100% in both treatment groups. Conclusions Our data suggest that, in SPK recipients, long-term kidney allograft survival and function are not statistically different. A trend toward an increased rate of renal allograft loss was found in the Tac/SRL-treated group.

Background Infarct size is increasingly used as an efficacy endpoint in randomized trials comparing acute myocardial infarct (AMI) therapies. Infarct size, depicted by delayedenhancement-CMR, is quantified using manual planimetry (MANUAL), visual scoring (VISUAL), or automated techniques using signal-intensity thresholding to define infarct borders (AUTO). Although AUTO is considered the most reproducible, prior studies did not account for the subjective determination of endocardial/epicardial borders, which all methods require. For MANUAL and VISUAL, prior studies have not explicitly defined how to treat intermediate signal-intensities due to partial volume. We wanted to assess sources of variability among 6 methods in quantification of AMI size, and illustrate the significance of these findings on sample size calculations for clinical trials.

Objectives We evaluated the ability of delayed enhancement magnetic resonance imaging (DE-MRI) to predict clinical response to cardiac resynchronization therapy (CRT). Background Cardiac resynchronization therapy reduces morbidity and mortality in selected heart failure patients. However, up to 30% of patients do not have a response. We hypothesized that scar burden on DE-MRI predicts response to CRT. Methods The DE-MRI was performed on 28 heart failure patients undergoing CRT. Patients with QRS ≥120 ms, left ventricular ejection fraction ≤35%, New York Heart Association functional class II to IV, and dyssynchrony ≥60 ms were studied. Baseline and 3-month clinical follow-up, wall motion, 6-min walk, and quality of life assessment were performed. The DE-MRI was performed 10 min after 0.20 mmol/kg intravenous gadolinium. Scar measured by planimetry was correlated with response criteria. Results Twenty-three patients completed the protocol (mean age 64.9 ± 11.7 years), with 12 (52%) having a history of myocardial infarction. Thirteen (57%) patients met response criteria. Percent total scar was significantly higher in the nonresponse versus response group (median and interquartile range of 24.7% [18.1 to 48.7] vs. 1.0% [0.0 to 8.7], p = 0.0022) and predicted nonresponse by receiver-operating characteristic analysis (area = 0.94). At a cutoff value of 15%, percent total scar provided a sensitivity and specificity of 85% and 90%, respectively, for clinical response to CRT. Similarly, septal scar ≤40% provided a 100% sensitivity and specificity for response. Regression analysis showed linear correlations between percent total scar and change in each of the individual response criteria. Conclusions The DE-MRI accurately predicted clinical response to CRT. This technique offers unique information in the assessment of patients referred for CRT.

Corticosteroids have been a component of maintenance immunosuppression for renal transplant since the 1960s and have helped to reduce the rate of acute rejection. Corticosteroids, however, have many adverse effects, and with the development of new immunosuppressive medications, many transplant centers have adopted protocols that eliminate or completely avoid the use of corticosteroids. Despite promising short-term results, the impact of corticosteroid elimination on long-term kidney function still is unclear. This single-center, retrospective, sequential study analyzed 212 renal transplant patients with a median follow-up of 5 yr. All patients received induction with IL-2 receptor antagonist and maintenance immunosuppression with mycophenolate mofetil and tacrolimus. Ninety-six patients were maintained on chronic prednisone, and 116 were maintained without chronic prednisone (rapid steroid elimination). Kaplan-Meier patient and graft survival at 7 yr after transplantation were not statistically different between the two groups. Rate and severity of acute cellular rejection were similar. Furthermore, the slope of GFR decline per month at 5 yr after transplantation was not statistically different between the two groups. Prednisone-treated patients had a significantly higher incidence of hyperlipidemia and posttransplantation diabetes when compared with patients with rapid steroid elimination. It was concluded that with the current immunosuppressive medications, the use of chronic prednisone to maintain long-term kidney function and prevent acute cellular rejection is not justified.

ObjectivesWe tested a pre-defined visual interpretation algorithm that combines cardiovascular magnetic resonance (CMR) data from perfusion and infarction imaging for the diagnosis of coronary artery disease (CAD).BackgroundCardiovascular magnetic resonance can assess both myocardial perfusion and infarction with independent techniques in a single session.MethodsWe prospectively enrolled 100 consecutive patients with suspected CAD scheduled for X-ray coronary angiography. Patients had comprehensive clinical evaluation, including Rose angina questionnaire, 12-lead electrocardiography, C-reactive protein, and calculation of Framingham risk. Cardiovascular magnetic resonance included cine, adenosine-stress and rest perfusion-CMR, and delayed enhancement-CMR (DE-CMR) for infarction imaging. Matched stress-rest perfusion defects in the absence of infarction by DE-CMR were considered artifactual. All patients underwent X-ray angiography within 24 h of CMR.ResultsNinety-two patients had complete CMR examinations. Significant CAD (≥70% stenosis) was found in 37 patients (40%). The combination of perfusion and DE-CMR had a sensitivity, specificity, and accuracy of 89%, 87%, and 88%, respectively, for CAD diagnosis, compared with 84%, 58%, and 68%, respectively, for perfusion-CMR alone. The combination had higher specificity and accuracy (p < 0.0001), owing to incorporating the exceptionally high specificity (98%) of DE-CMR. Receiver operating characteristic curve analysis demonstrated the combination provided better performance than cine, perfusion, or DE-CMR alone. The accuracy was high in single-vessel and multivessel disease and independent of CAD location. Multivariable analysis including standard clinical parameters demonstrated the combination was the strongest independent CAD predictor.ConclusionsA combined perfusion and infarction CMR examination with a visual interpretation algorithm can accurately diagnose CAD in the clinical setting. The combination is superior to perfusion-CMR alone.

Background. Chronic renal failure (CRF) is a major cause of morbidity and mortality after orthotopic liver transplantation (OLTX) and is predominantly caused by calcineurin inhibitors (CI)-induced nephrotoxicity. The activation of the renin angiotensin system (RAS) has been implicated in the pathogenesis of chronic nephrotoxicity from CI. Methods. We retrospectively investigated the genes coding for components of the RAS (ACE gene, Angiotensin II receptor 1 gene, Angiotensinogen gene) in 233 liver transplant recipients receiving Cyclosporine (CsA) or Tacrolimus (Tac) as maintenance immunusuppressant. All patients with serum creatinine (sCr)

The impact of a prednisone-free immunosuppressive regimen was evaluated in simultaneous pancreas-kidney (SPK) recipients. Patient and graft survivals, rejection rates and the incidence of CMV disease were determined. Two hundred consecutive SPK transplant recipients received tacrolimus-based immunosuppression with (n = 100) or without (n = 100) chronic prednisone therapy. Patients were induced with lymphocyte depleting antibodies or IL-2 receptor blockers and received prophylactic antiviral therapy. Patient and graft survivals and rejection rates were not statistically significantly different between treatment groups. Two-year cumulative incidence of CMV in recipients in the prednisone-free protocol was reduced (7.2% vs. 16%; p = 0.15). Considering only recipients at highest risk (D+/R- or D+R+), incidence of CMV disease in the prednisone-free group (n = 61) compared to the steroid-treated group (n = 48) was reduced from 36% to 18% (p < 0.05). Multivariate analysis confirmed the independent effect of prednisone treatment on the incidence of CMV (RR 2.3; p = 0.04). In the prednisone-free protocol, incidence of CMV was less frequent in recipients receiving induction with Campath versus rabbit antilymphocyte globulin (2.4% vs. 12.6%; p = 0.14). Eliminating prednisone immunotherapy did not adversely affect outcomes and was associated with a reduced rate of CMV in SPK recipients of organs from sero-positive donors.

This study examined alemtuzumab (anti-CD 52, Campath-1H) and basiliximab (anti-CD 25, Simulect) as induction immunosuppression in kidney transplantation. We used a single-center, nonrandomized, retrospective, sequential study design to evaluate outcomes in kidney transplant recipients given either alemtuzumab (n = 123) or basiliximab (n = 155) induction in combination with a prednisone-free maintenance protocol using tacrolimus and mycophenolate mofetil. Kaplan-Meier analyses of long-term patient and graft survivals and rejection rates were determined according to induction agent, donor source and recipient ethnicity. Secondary endpoints included the quality of renal allograft function and the etiology of infectious complications. Overall long-term patient and graft survival rates did not significantly differ between patients treated with alemtuzumab and basiliximab. A lower rate of early (

Stem cells possess enormous therapeutic potential in tissue replacement. To study stem cells further, they must be isolated. Techniques are available for enrichment and study of hematopoietic stems cells, but thus far, techniques for purification of spermatogonial stem cells have not been described. Enrichment techniques for hematopoietic stem cells include the use of fluorescence-activated cell sorter analysis with Hoechst 33342 and rhodamine 123 (Rho) dyes. Use of Hoechst dye to isolate spermatogonial stem cells has been unsuccessful in our laboratory, and our results have conflicted with those from other laboratories. Taking advantage of the differential staining of the Rho dye, we report a novel method to enrich murine spermatogonial stem cells. Testicular cells are harvested from cryptorchid ROSA26 male mice. Populations of these cells are then stained with the Hoechst and Rho dyes, allowing them to be sorted by flow cytometry into a side population (SP) of Hoechst low-intensity cells and populations of low (Rho low ) or high (Rho hi ) fluorescent intensity. Sterile recipients, W/W v mice, with an intrinsic germ cell deficiency were transplanted with the Hoechst SP cells, Rho low , Rho hi , and nonsorted donor cells. No spermatogonial stem cell colonies were derived from the Hoechst SP cells. The number of spermatogonial stem cell colonies from transplanted Rho low cells showed a 17- and 20-fold enrichment over those of Rho hi and nonsorted cells, respectively. male reproductive tract, sperm, spermatogenesis, testis

Background— In some patients with heart failure, β-blockers can improve left ventricular (LV) function and reduce morbidity and mortality. We hypothesized that gadolinium-enhanced cardiovascular magnetic resonance imaging (CMR) can predict reversible myocardial dysfunction and remodeling in heart failure patients treated with β-blockers. Methods and Results— Forty-five patients with chronic heart failure underwent CMR. Contrast imaging using gadolinium was performed to obtain high-resolution spatial maps of myocardial scarring and viability. Cine imaging was performed to assess LV function and morphology and was repeated in 35 patients after 6 months of β-blockade. Gadolinium CMR demonstrated scarring in 30 of 45 patients (67%). Scarring was found in 100% of patients with ischemic cardiomyopathy (28 of 28) but in only 12% with nonischemic cardiomyopathy (2 of 17). In the 35 patients who were maintained on β-blockers and had a second study, there was an inverse relation between the extent of scarring at baseline and the likelihood of contractile improvement 6 months later ( P 75% scarring (8 of 232). Multivariate analysis showed that the amount of dysfunctional but viable myocardium by CMR was an independent predictor of the change in ejection fraction ( P =0.01), mean wall motion score ( P =0.0007), LV end-diastolic volume index ( P =0.007), and LV end-systolic volume index ( P ≤0.0001). Conclusions— For heart failure patients treated with β-blockers, gadolinium-enhanced CMR predicts the response in LV function and remodeling.

Myocardial infarcts are routinely detected by nuclear imaging techniques such as single photon emission computed tomography (SPECT) myocardial perfusion imaging. A newly developed technique for infarct detection based on contrast-enhanced cardiovascular magnetic resonance (CMR) has higher spatial resolution than SPECT. We postulated that this technique would detect infarcts missed by SPECT.We did contrast-enhanced CMR and SPECT examinations in 91 patients with suspected or known coronary artery disease. All CMR and SPECT images were scored, using a 14-segment model, for the presence, location, and spatial extent of infarction. To compare each imaging modality to a gold standard, we also acquired contrast-enhanced CMR and SPECT images in 12 dogs with, and three dogs without, myocardial infarction as defined by histochemical staining.In animals, contrast-enhanced CMR and SPECT detected all segments with nearly transmural infarction (75% transmural extent of the left-ventricular wall). CMR also identified 100 of the 109 segments (92%) with subendocardial infarction (50% transmural extent of the left-ventricular wall), whereas SPECT identified only 31 (28%). SPECT and CMR showed high specificity for the detection of infarction (97% and 98%, respectively). In patients, all segments with nearly transmural infarction, as defined by contrast-enhanced CMR, were detected by SPECT. However, of the 181 segments with subendocardial infarction, 85 (47%) were not detected by SPECT. On a per patient basis, six (13%) individuals with subendocardial infarcts visible by CMR had no evidence of infarction by SPECT.SPECT and CMR detect transmural myocardial infarcts at similar rates. However, CMR systematically detects subendocardial infarcts that are missed by SPECT.

This study was designed to assess the effects of tachycardia origin, the significance of atrial contribution, and the effects of left ventricular ejection fraction on hemodynamically tolerated ventricular tachycardia (VT) and supraventricular tachycardia (SVT). Forty-one subjects with inducible hemodynamically tolerated VT (n = 24) or SVT (n = 17) with mean ages of 60 +/- 13 and 40 +/- 16 years and mean ejection fractions of 32 +/- 15% and 59 +/- 5%, respectively, were studied. VT and SVT were induced by standard techniques, and femoral arterial blood pressure (BP) was recorded for 30 seconds. After tachycardia termination, with >/=3 minutes between conditions, ventricular overdrive pacing was performed from the right ventricular (RV) apex and then the RV outflow tract, followed by atrioventricular (AV) pacing at the tachycardia cycle length. Mean BP was measured every 5 seconds. Linear regression methods were used to model BP response for the 2 groups. There was a significant increase in BP over the 20-second interval after the induction of VT and SVT (0.55 +/- 0.21 and 1.0 +/- 0.20 mm Hg/s, respectively, p

BACKGROUND We examined the feasibility of rapid corticosteroid elimination in simultaneous pancreas kidney transplantation. METHODS Forty consecutive simultaneous pancreas-kidney (SPK) transplant recipients were enrolled in a prospective study in which antithymocyte globulin induction and 6 days of corticosteroids were administered along with tacrolimus and MMF (n=20) or tacrolimus and sirolimus (n=20). Mean+/-SD follow-up for recipients receiving tacrolimus/MMF and tacrolimus/sirolimus were 12.7+/-3.9 and 13.4+/-2.9 months, respectively. Patient and graft survival, and rejection rates were compared to an historical control group (n=86; mean follow-up 41.5+/-15.4 months) of SPK recipients that received induction and tacrolimus, MMF, and corticosteroids. RESULTS Demographic characteristics of recipient and donor variables were similar among all groups. The 1-year actuarial patient, kidney, and pancreas survival rates in the 40 SPK transplant recipients with rapid corticosteroid elimination were 100, 100, and 100%, respectively. In the historical control group the 1-year actual patient, kidney, and pancreas survival rates were 96.5, 93.0, and 91.9%, respectively. The 1-year rejection-free survival rate recipients in the rapid steroid elimination group collectively was 97.5 vs 80.2% in the historical control group (P=0.034). At 6 and 12 months posttransplant the serum creatinine values remained stable in all groups. CONCLUSIONS We conclude that chronic corticosteroid exposure is not required in SPK transplant recipients receiving antithymocyte globulin induction and maintenance immuno-suppression consisting of either tacrolimus and mycophenolate mofetil or tacrolimus and sirolimus.

Background. The relevance of cytomegalovirus (CMV) in simultaneous pancreas kidney (SPK) transplant recipients in the modern era of immunosuppression and antiviral therapeutics is largely unquantified. We sought to determine the risk factors of CMV disease and its impact on SPK transplant outcomes in recipients all receiving a consistent regime of maintenance immunosuppression and CMV prophylaxis. Methods. This is a retrospective, single center study of 100 consecutive SPK transplant recipients. All received maintenance immunosuppression with mycophenolate mofetil, tacrolimus, and prednisone. CMV prophylaxis consisted of a short course of parenteral gancyclovir followed by oral gancyclovir. Recipients at high-risk (D+/R−) for CMV also received CMV hyperimmune globulin. Multivariate analysis of risk factors for CMV disease and risk factors for adverse outcomes in SPK transplantation were determined. The effect of duration of prophylaxis on timing and severity of CMV disease in high-risk (D+/R−) SPK transplant recipients was also evaluated. Results. The actual 1-year rate of CMV disease was 17.0% (12.0% noninvasive, 5.0% tissue invasive); and according to donor and recipient CMV serological status was: D−/R+: 0%; D−/R−: 2.8%; D+/R+: 25.6%; and D+/R−: 40.6%. Multivariate analysis showed transplantation of organs from a donor with positive CMV serology to be predictive of CMV disease with a relative risk of 63.37 (P =0.0052). In the high-risk (D+/R−) subgroup, the duration of prophylactic therapy delayed onset of CMV disease, but had minimal effect on severity. Invasive CMV disease was an independent predictor of mortality but did not decrease kidney or pancreas allograft survival. Conclusions. Outcomes of SPK transplantation have improved in the current era of modern immunosuppression, yet CMV remains an important pathogen. The serological status of the organ donor and the duration of CMV prophylaxis are predictive of who and when CMV disease may occur. Nevertheless, new strategies that reduce risk and severity of CMV disease are still needed.

Background —Baroreflex-mediated parasympathetic stimulation has variable effects on heart rate variability (HRV). We postulated that a quadratic function would describe the relationship between HRV and parasympathetic effect better than a linear function. Methods and Results —Twenty-nine normal volunteers (15 women; mean age 39±12 years) were studied after β-adrenergic blockade with intravenous propranolol. Five-minute ECG recordings were made during graded infusions of phenylephrine and nitroprusside to achieve baroreflex-mediated increases and decreases in parasympathetic effect, respectively. Time- and frequency-domain measures of HRV were calculated from the R-R interval tachograms. The R-R interval and the vagal-sympathetic effect (VSE=R-R interval/intrinsic R-R interval) were used as indices of parasympathetic effect. The data were fit to both quadratic and linear models. In each case, the quadratic model (with a negative coefficient for the squared term) was superior to the linear model. There was some evidence that age influenced the responsiveness of the HRV parameters with changing parasympathetic effect, although the regression analysis was significant only in the models for MSSD ( P P Conclusions —The relationship between HRV and parasympathetic effect is best described by a function in which there is an ascending limb where HRV increases as parasympathetic effect increases until it reaches a plateau level; HRV then decreases as parasympathetic effect increases. Because there is marked interindividual variation in this relationship, differences in HRV between individuals may reflect differences in this relationship and/or differences in autonomic effects.

Introduction: Recent increases in the rate of carotid endarterectomies (CEAs) have been attributed to results of clinical trials demonstrating efficacy when CEA is performed in centers of excellence. Subsequent population-based data suggest that trial results may not be matched in the community. This study was undertaken to characterize trends in CEA procedure rates after the dissemination of trial data and to describe any change in patient outcomes with population-based data from a single state. Methods: Hospital administrative data on CEAs from 1992 to 1996 (n = 45,744) were obtained for the state of Florida. Annualized CEA rates per 100,000 Florida residents were analyzed to determine trends in patient age, sex, admission type, size of hospital beds, ownership type and teaching status, and annual hospital and surgeon CEA volume. Outcomes were examined to track trends in complication rates. Results: The annual number of CEA procedures increased 74% from 63.7 per 100,000 residents per year to 110.8 per 100,000 residents per year between 1992 and 1996. A single large increase occurred during the second half of 1994 when CEAs increased 73.5% from 16.6 per 100,000 residents per quarter to 28.8 per 100,000 residents per quarter after a clinical alert on benefits to CEAs in asymptomatic patients. Over 5 years, there were significant trends toward more nonemergent admissions, and more procedures were performed in high-volume hospitals and by high-volume surgeons. Procedure rates in both women and very elderly patients increased more than 70%, which was in step with younger patients and men. The incidence of inpatient stroke and death declined over the 5-year period, whereas the rate of perioperative myocardial infarction remained constant. Conclusions: Experience from Florida indicates that CEA rates increased as results of the Asymptomatic Carotid Artery Study disseminated. Trial results have been broadly interpreted to include women and very elderly patients. More patients are being referred to busier hospitals and to high-volume surgeons, which should continue to result in better patient outcomes. (J Vasc Surg 2000;31:901-9.)

Chronically instrumented dogs underwent 2- or 5-h regional reductions in coronary flow that were followed, respectively, by balanced reductions in myocardial contraction and O2consumption (“hibernation”) and persistently reduced contraction despite normal myocardial O2consumption (“stunning”). Previously unidentified myofibrillar disruption developed during flow reduction in both experimental models and persisted throughout the duration of reperfusion (2–24 h). Aberrant perinuclear aggregates that resembled thick filaments and stained positively with a monoclonal myosin antibody were present in 34 ± 3.8% (SE) and 68 ± 5.9% of “hibernating” and “stunned” subendocardial myocytes in areas subjected to flow reduction and in 16 ± 2.5% and 44 ± 7.4% of subendocardial myocytes in remote areas of the same ventricles. Areas of myofibrillar disruption also showed glycogen accretion and unusual heterochromatin clumping adjacent to the inner nuclear envelope. The degrees of flow reduction employed were sufficient to reduce regional myofibrillar creatine kinase activity by 25–35%, but troponin I degradation was not evident. The observed changes may reflect an early, possibly reversible, phase of the myofibrillar loss characteristic of hypocontractile myocardium in patients undergoing revascularization.

We evaluated the prevalence of valvular regurgitation in patients who have taken anorectic medications. Two-dimensional echocardiograms with color flow Doppler were recorded in 200 consecutive patients referred to a major metropolitan hospital for evaluation of cardiac function because of a history of anorectic medication use. Each patient filled out a questionnaire at the time of the visit or through telephone contact. Each echocardiogram was reviewed by 2 observers. The degree of valvular regurgitation was graded by a consensus of both observers. Significant valvular regurgitation was defined as at least moderate mitral regurgitation (MR) or at least mild aortic regurgitation (AR), as recommended by the Food and Drug Administration and Centers for Disease Control and Prevention. For all patients having taken anorectic drugs, there was a 5% prevalence of at least moderate MR, a 12% prevalence of at least mild AR, and a 16% prevalence of significant MR and/or AR. Patients with significant AR and/or MR were older than those without significant valvular regurgitation (49 ±12 vs 44 ± 11 years, p = 0.03). Patients with significant MR and/or AR had a longer exposure duration (8 vs 6 months, p = 0.049) to anorectic drugs. There was no difference in weight loss between those with and without significant regurgitation (p = NS). The 2 largest subgroups were patients who took the fenfluramine-phentermine combination (n = 127) and those who took dexfenfluramine alone (n = 42). The prevalence of significant MR and AR was 5% and 9% for the fenfluramine-phentermine group and 0% and 14% for the dexfenfluramine group, respectively. There was also a high subthreshold level of MR and AR in these patients.