Cardiac MRIs Research Articles

Abstract 18878: Development of a Unique Mode of Cardiac Remodeling in Muscular Dystrophy Patients

The muscular dystrophies (MD) represent an array of inherited myogenic disorders involving mutations and dysregulations of a variety of cytoskeleton or nuclear proteins. Many MD patients also develop a commitant cardiomyopathy. Despite the high incidence of end-stage cardiomyopathy in MD patients there is limited data regarding the mode of maladaptive cardiac remodeling that develops in these patients. In this retrospective study, we examined the hypothesis that MD patients with a cardiomyopathy develop a unique mode of cardiac remodeling as compared to patients with other forms of nonischemic cardiomyopathy. We examined the cardiac MRIs of 3 cohorts (N = 35 per cohort): patients with neuromuscular disorders with associated cardiomyopathy; patients with primary idiopathic nonischemic cardiomyopathy (NICM); and healthy patients from the Dallas Heart Study (DHS). The cardiac MRIs in each group were reviewed, assessing objective measurements of left ventricular ejection fraction (LVEF), mass (LVM), and end diastolic volume (LVEDV). LVM and LVEDV were indexed for body surface area. In addition, left ventricular concentricity 0.67 (LV Conc 0.67 = LVM / LVEDV 0.67 ), a surrogate marker for wall thickness known to decrease in advanced nonischemic heart failure, was computed for each patient. Despite a preserved ejection fraction in the neuromuscular cohort compared to the NICM cohort (58% vs. 30 %, p<0.05), both displayed similar reduced LV Conc 0.67 (4.69 ± 1.05 and 5.16 ± 1.47) compared to the DHS cohort (7.27 ± 0.83). However, whereas the nonischemic cohort demonstrated hypertrophy with marked dilation (95.8 vs. 84.6 g/m 2 and 119.4 vs. 54.7 mL/m 2 , DHS comparison, p<0.05), the neuromuscular cohort demonstrated a reduced cardiac mass (65.6 vs. 84.6 g/m 2 , p<0.05) with only moderate dilation (74.5 vs. 54.7 mL/m 2 , p<0.05) compared to the DHS population. In conclusion, our data suggests that MD patients develop a unique mode of cardiac remodeling and highlights that novel signaling pathways are involved in the development of cardiomyopathy in these patients.

Quantitative T2 mapping for detecting myocardial edema after reperfusion of myocardial infarction: validation and comparison with T2-weighted images

This study evaluates the clinical usefulness of T2 mapping for the detection of myocardial edema in the re-perfused acute myocardial infarction (MI). Cardiac MRIs were reviewed in 20 patients who had acute MI after reperfusion therapy. The regional T2 values and T2-weighted image (T2WI) signal intensities (SI) were measured in the infarcted and remote zones of the myocardium. Patients were divided into three groups according to the signal patterns of the infarcted myocardium on the T2WIs. The T2 values of the infarcted zones were compared on the T2 maps among the three groups. Validation of the T2 values was performed in the normal myocardium of seven healthy volunteers. There were no significant differences in mean T2WI-SI or T2 values in the normal myocardium of healthy volunteers compared to the remote myocardium of acute MI patients (p > 0.05). Mean SI on the T2WIs was significantly higher in the infarcted myocardium (81.3 ± 37.6) than in the remote myocardium (63.8 ± 18.1) (p < 0.05). The T2WIs showed high SI in ten patients (group 1), iso-SI in seven (group 2), and low SI in three (group 3) in the infarcted myocardium, compared to the remote myocardium. The T2 maps showed that T2 values in the infarcted myocardium had mostly increased, regardless of group, with values of 71 ± 9 ms in group 1, 64.9 ± 7.4 ms in group 2, and 61.4 ± 8.5 ms in group 3. T2 mapping is superior to T2WI for detecting areas of high SI in the infarcted myocardium. Therefore, quantitative T2 mapping sequences may be more useful and reliable in identifying myocardial edema in the infarcted myocardium than T2WI.

Feature tracking strain is a promising functional analysis technique in single ventricle patients

Background Feature-tracking Strain (FT S) is a new technique that performs myocardial Strain evaluation on Steady State Free Precession (SSFP) cines without the need for myocardial tagging. As a pilot study to determine whether FT S may be useful in single ventricle patients, we applied this analysis to patients with hypoplastic left heart syndrome (HLHS) and tricuspid atresia (TA). Methods We retrospectively reviewed 22 patients with a history of Fontan palliation (median age 8.2, range 2 - 27.5 years) who had cardiac MRIs with a Siemens 1.5 Tesla Avanto (Siemens Medical Systems) scanner, 11 with TA, 11 with HLHS. All had steady-state free precession (SSFP) sequences of 4-chamber (4ch) cine and short axis (SAx) cine stacks from cardiac base to apex. Ejection fraction (EF) was calculated from the SAx stack on a Leonardo workstation (Siemens, Inc.). FT S analysis of the 4ch cine was performed off-line with TomTec 2D Cardiac Performance Analysis (version 1.0, TomTec Imaging Systems) following two tracking protocols: endocardial trace only (Endo), epicardial to endocardial trace (Endo-Epi) (Figure 1). Pearson correlation was used to test relationship between absolute global longitudinal Strain (GLSabs) and EF. Differences in GLS between tracking methods were tested with Bland Altman analysis. Results Mean EF was 60.2%, 95% CI 42.6% to 77.8%. Mean GLS was -15.7 (95% CI -6.8 to -24.7) by Endo., and -16.5 (95% CI -6.9 to -26.1) by Endo-Epi tracking methods. There was fair correlation (Figure 2) between GLSabs and EF using the Endo method (Pearson r = 0.67, p mean Endo GLS of 0.8, with a wide distribution in difference values, 95% CI 2.9 to -4.5. Morphologic ventricle type (single LV vs single RV) did not make a difference in GLS to EF correlations when compared to the mixed cohort. Mean GLS for single LVs was somewhat higher than single RVs, but this difference did not reach statistical significance. Conclusions There is fair correlation between GLS and EF in single ventricle patients with feature-tracking Strain analysis tracking the ventricular endocardium. Validation in a larger sample is warranted. Comparison of FT S with tagged harmonic phase MRI in single ventricle patients may further validate this promising technique in defining regional and global strain. Funding

FLOOR: fusing locally optimal registrations.

Most registration algorithms, such as Demons, align two scans by iteratively finding the deformation minimizing the image dissimilarity at each location and smoothing this minimum across the image domain. These methods generally get stuck in local minima, are negatively impacted by missing correspondences between the images, and require careful tuning of the smoothing parameters to achieve optimal results. In this paper, we propose to improve on those issues by choosing the minimum from a set of candidates. Our method generates such candidates by running the registration algorithm multiple times varying the setting of the smoothing and the image domain. We iteratively refine those candidates by fusing them with the outcome of alternative approaches and locally adapting the smoothing parameters. We implement our algorithm based on Demons and find alternative minima via manifold learning. Compared to those two methods, our 600 pairwise registrations of cardiac MRIs significantly better handle the large shape variations of the heart and the different field of views captured by scans.

Abstract 19208: Higher Cornell Product and QTc on Exercise Stress Testing are Correlated with Lower Cardiac MRI T1 Times in Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is characterized by ventricular hypertrophy, myocyte disarray and interstitial fibrosis which result in arrhythmias, sudden death and heart failure. Studies have shown that the resting EKG can be used to predict abnormalities on contrast enhanced cardiac MRIs. However, studies correlating changes seen in the EKG during exercise and measurements on MRIs in the HCM population have not been studied. The exercise state is clinically relevant for patients with HCM and exercise stress testing is an economical tool that is often abnormal in HCM patients. We assessed the hypothesis that during the exercise state changes in various EKG parameters such as the Cornell product, for example, would correlate with lower T1 times on contrast enhanced MRIs. One hundred and sixty three patients (67% male) were evaluated fulfilling standard HCM criteria and clinical history was obtained. EKGs from Bruce protocol treadmill stress testing were independently analyzed for heart rate, QRS duration, LVH criteria including Sokolow-Lyon and Cornell product, ST changes, T wave inversions, and strain pattern. Contrast enhanced MRIs were performed and T1 mapping was analyzed independently. As shown in Table 1, compared to the rest state, peak exercise EKGs showed higher Cornell product, QTc, QRS duration, greater presence of strain pattern, and non-specific ST depressions and T wave inversions (p &lt; 0.001 in all groups). The Cornell product (r = -0.71 for rest, r = -0.86 for exercise state) and QTc (r = -0.62 for rest, r = -0.74 for exercise) were correlated with lower T1 times. In conclusion, the novel findings of this study are that abnormalities in parameters such as the Cornell product or QTc correlate with lower T1 times on MRI, especially in the exercise state. Lower T1 times are associated with greater fibrosis and abnormalities in repolarization or conduction (as seen in EKGs during the exercise state) could indicate a subpopulation of HCM patients at greater risk.

Assessment of cell infiltration in myocardial infarction: A dose-dependent study using micrometer-sized iron oxide particles

Myocardial infarction (MI) is a leading cause of death and disabilities. Inflammatory cells play a vital role in the process of postinfarction remodeling and repair. Inflammatory cell infiltration into the infarct site can be monitored using T 2-weighted MRI following an intravenous administration of iron oxide particles. In this study, various doses of micrometer-sized iron oxide particles (1.1-14.5 μg Fe/g body weight) were injected into the mouse blood stream before a surgical induction of MI. Cardiac MRIs were performed at 3, 7, 14, and 21 days postinfarction to monitor the signal attenuation at the infarct site. A dose-dependent phenomenon of signal attenuation was observed at the infarct site, with a higher dose leading to a darker signal. The study suggests an optimal temporal window for monitoring iron oxide particles-labeled inflammatory cell infiltration to the infarct site using MRI. The dose-dependent signal attenuation also indicates an optimal iron oxide dose of approximately 9.1-14.5 μg Fe/g body weight. A lower dose cannot differentiate the signal attenuation, whereas a higher dose would cause significant artifacts. This iron oxide-enhanced MRI technique can potentially be used to monitor cell migration and infiltration at the pathological site or to confirm any cellular response following some specific treatment strategies.

Overdiagnosis of Left Ventricular Noncompaction

Introduction: Left ventricular noncompaction (LVNC) is characterized by prominent left ventricular trabeculations and deep intertrabecular recesses, and is classically described as carrying a grave prognosis. Common clinical characteristics include young age, risk of systemic thromboembolism, ventricular arrhythmias, and inexorable progression toward death or transplantation. The goal of this study was to identify all cases of LVNC and ‘prominent trabeculation’ (TRN) diagnosed at our institution over a ten year period, and to attempt to validate the diagnoses. Hypothesis: As improved echocardiographic technology has allowed for easier identification of ventricular trabeculae, LVNC and TRN are being overdiagnosed. Methods: Echocardiography reports from 1999–2009 at our institution with TRN and/or LVNC were termed “positive,” and any reports without notation of TRN and/or LVNC in this cohort of patients were termed “negative.” In addition, we reviewed all charts for concomitant cardiac MRIs and cardiac transplant status. We evaluated a) the consistency with wich LVNC or TRN were noted on echocardiograms on the same patients, and b) concordance with other diagnostic modalities (cardiac MRI and pathology from explanted hearts). Results: 709 patients had a total of 1428 echocardiograms, of which 1015 were positive. 71% of the cohort was male (n = 505), and the average age was 61 years. 19% of positive echocardiograms (n = 1015) occurred in patients with relatively preserved systolic function (LVEF > 45%). Out of 466 patients (66% of the cohort) with repeat echocardiograms during the time period studied, 12% had consistently positive repeat echocardiograms, 63% had consistently negative repeat echocardiograms, and 25% had a mixture of positive and negative echocardiograms. Out of 48 patients who subsequently underwent cardiac transplantation, only 3 (6%) had TRN or LVNC confirmed on pathology review. Of 51 patients who underwent cardiac MRI, 8 (16%) confirmed the presence of TRN or LVNC. Conclusion: In our study cohort, there was little reproducibility for a diagnosis of LVNC or TRN by echocardiography, and very little correlation with findings on cardiac MRI or pathology. In addition, the clinical characteristics of the study population were very distinct from the classical description of patients with LVNC. Given the clinical and psychological ramifications of labeling a patient with these diagnoses, we urge reconsideration of the diagnostic criteria.

Listening to syncope

A 35-year-old man presented with progressive exertional dyspnea (3 months) and syncopal attacks (1 week). He had tachypnea, tachycardia and hypotension. Examination revealed a mid-diastolic plop at the apex. Clinical suspicion was a left atrial mass with a ball valve-like mechanism (LA thrombus or LA tumors). Echo and cardiac MRIs with gadolinium enhancement (to differentiate between a tumor and thrombus) were considered as necessary investigations. An emergency echo revealed a large mass (8.0×3.5 cm) in the left atrium arising from the roof. It was prolapsing through the mitral valve, compromising LV inflow. There were no embolic manifestations or features of NAME (nevi, atrial myxoma, myxoid neurofibromas, ephelides) or LAMB (lentigenes, atrial myxoma, blue nevi) syndromes or Carney’s complex. The patient underwent surgery. The excised mass was conical, and histopathology revealed myxomatous areas with vascular channels and cellular areas. This was diagnosed as a cellular variant of angiomyxoma (a rare variant). The patient recovered with no complications and was discharged after 1 week of observation. Atrial myxoma is the most common benign primary tumor of the heart. The majority of them are solitary and occur in the left atrium in the zone of the fossa ovalis. Common symptoms are dyspnea and syncope. Other presentations include PUO, weight loss, embolic manifestations and arrhythmias. Definitive treatment is always surgery. The present case emphasizes the clinical significance of cardiac auscultation in a patient who presents with syncope. Int J Emerg Med (2009) 2:125–126 DOI 10.1007/s12245-009-0095-x

257: The COMPASS-3 Study: Utilizing Hemodynamics and Non-Invasive Measures (c-MRI) To Evaluate Baseline Severity in Pulmonary Arterial Hypertension (PAH)

The COMPASS-3 trial is a prospective, multi-center study evaluating a goal based approach to combinational therapy in PAH. As prognosis ultimately depends on the degree of right ventricular (RV) dysfunction, RV remodeling will be evaluated by serial cardiac MRIs and correlated with clinical, invasive and non-invasive parameters. Reported herein are the baseline characteristics of the initial 47 enrolled patients as of August 1 2008.

Abstract 5105: The Relationship of Inflammation and Thrombosis with Right Ventricular Mass and Function: The MESA-Right Ventricle Study

Right ventricular (RV) mass reflects response to afterload, whereas RV ejection fraction (RVEF) is an indicator of RV function. Pulmonary vascular disease is characterized by hemostatic abnormalities and inflammation and may affect RV mass and function. We hypothesized that increased levels of inflammatory markers (ICAM-1, TNF-α, E-Selectin, MMP-3, and MMP-9) would be associated with higher RV mass and lower RVEF, and increased levels of hemostatic markers (tissue factor, PAI-1, and CD40L) and decreased levels of TFPI would be associated with higher RV mass and lower RVEF. The Multi-Ethnic Study of Atherosclerosis (MESA) performed interpretable cardiac MRIs on 5,004 participants without clinical cardiovascular disease at six field centers. 785 randomly selected patients had plasma biomarkers measured, 730 of whom had complete interpretation of RV measures. Endocardial margins of the RV were manually contoured on diastolic and systolic images. End-diastolic volume (EDV) and end-systolic volume (ESV) were calculated by using a summation of disks method (“Simpson’s Rule”). RVEF was calculated from (EDV-ESV)/EDV. RV mass was determined from cine images of the heart. Biomarkers were analyzed in quintiles using multivariate linear regression. The 730 participants in the study sample were 59 ± 10 (mean ± SD) years old, 58% female, 45% Caucasian, 21% African-American, 11% Chinese-American, and 23% Hispanic. The RV mass was 22 g ± 5 g and RVEF was 69% ± 7%. Higher PAI-1 levels were associated with lower RV mass, after adjustment for age, gender, race, height, and weight (test for trend, p = 0.036, n = 710). Higher MMP-9 levels were associated with lower RV mass (test for trend, p = 0.006). Neither hemostatic nor inflammatory biomarkers were associated with RVEF. RV mass was inversely associated with PAI-1, a serine protease which inhibits thrombolysis, and MMP-9, which breaks down the extracellular matrix. The mechanism of these determinants of RV structure and function should be investigated.

Three-Tesla Cardiac Magnetic Resonance Imaging for Preterm Infants

We aimed to establish the feasibility of acquiring 3.0-T cardiac MRIs without sedation, anesthesia, or breath-holding for preterm infants and to obtain preliminary quantitative data on left ventricular function in this population. Twelve preterm infants underwent 3.0-T cardiac MRI without sedation or breath-holding. The median gestational age was 29 weeks (range: 26-33 weeks), the median birth weight was 1240 g (range: 808-2200 g), and the median postconceptional age at the time of cardiac MRI was 33 weeks (range: 31-40 weeks). Anatomic images were acquired with T2-weighted spin-echo sequences, and ventricular function was assessed with balanced steady-state free precession cine sequences. We assessed left ventricular function by using the area-length ejection fraction method on horizontal long-axis images and the volumetric Sergeant's discs method of analysis on short-axis images. Imaging was successful for 10 of 12 infants. For those 10, the area-length ejection fraction method in the horizontal long-axis plane estimated median stroke volume at 2.9 mL, cardiac output at 0.4 L/minute, end-diastolic volume at 3.8 mL, end-systolic volume at 0.3 mL, and ejection fraction at 74.6%. Short-axis volumetric estimations were made for 4 infants. With this approach, the median stroke volume was 2.4 mL, cardiac output 0.35 L/minute, end-diastolic volume 4.3 mL, end-systolic volume 2.1 mL, and ejection fraction 56%. Three-tesla cardiac MRI is feasible for preterm infants without sedation, anesthesia, or breath-holding and has the potential to provide a wide range of precise quantitative data that may be of great value for the investigation of cardiac function in preterm infants.

A report of cardiac events in a phase II clinical study using trastuzumab combined with pertuzumab in HER2-positive metastatic breast cancer (MBC)

1028 Background: T and P are humanized recombinant monoclonal antibodies (MoAB) that target different epitopes of HER2 extracellular domain. P blocks HER2’s ability to heterodimerize with other HER/ErbB receptors. Methods: This Ph II trial evaluates the efficacy and safety of T with P in patients (pts) with HER2+ (FISH +) MBC who had progressive disease (PD) on T-based therapy. Eligible pts must have had = 3 T-based regimens, normal (nl) left ventricular ejection fraction (EF=55%) and without significant cardiac history. Pts received IV T (6mg/kg) and P (420 mg) every 3 weeks (wks). EKG plus echocardiogram (ECHO) or cardiac MRI and tumor response were assessed every 3 and 6 wks, respectively. Results: Eleven pts received 39 (1 to 13) cycles, 1 pt achieved a partial response (PR) and 3 pts had stable disease. A total of 68 ECHOs and 8 cardiac MRIs were performed. Left ventricular systolic dysfunction (LVSD) with nl EKG was seen in 5 pts; Grade (Gr) 1 (n = 2) (EF 50–55%), Gr 2 (n = 2) (EF 40–50%) and Gr 3 (n = 1) (EF20–40%). Gr 2–3 events were associated with global hypokinesis. Gr 3 event was associated with symptomatic CHF. All 5 pts had received 240mg/m2 cumulative dose of doxorubicin, 2 pts (Gr 2–3) received chest wall radiation, and 1 pt (Gr 1) had HTN. Two pts with Gr 1–2 LVSD had a history of reduced EF during prior T-based treatment, which reversed to nl upon stopping T. Reduced EF appeared within 1–2 cycles, which returned to nl in 3 pts within 1wk to 3 months (mo) post discontinuing T/P. One pt had persistent Gr 2 LVSD 3 mo after the initial event. The pt with Gr 3 LVSD had extensive chest wall disease and died of PD and possibly CHF 2 mo after treatment termination. Conclusions: We observed Gr 1–3 LVSD in patients with HER2+ MBC who received dual MoAB treatment directed at HER2, in which very strict cardiac surveillance guidelines were required. One of 11 pts achieved PR and 1 pt had symptomatic CHF thus far. It is unknown whether the other events would have become symptomatic if treatment had continued. Further evaluation of the efficacy of combination T with P is required to define the overall risk and benefit. No significant financial relationships to disclose.

Structural Heart Disease, SCN5A Gene Mutations, and Brugada Syndrome

The report of the Second Consensus Conference, published in Circulation in 2005, defined the Brugada syndrome as ST-segment elevation in the right precordial ECG leads (so-called type 1 ECG) and a high incidence of sudden death in patients with structurally normal hearts.1 An autosomal dominant disease with incomplete penetrance, Brugada syndrome has been linked to mutations in SCN5A , the gene encoding the alpha subunit of the cardiac sodium channel.2 More than 80 mutations in SCN5A have been linked to this syndrome (references cited in Reference 1). Analysis of several of these mutations has consistently demonstrated a loss of function related to multiple mechanisms, including failure of sodium channel protein expression and changes in the voltage and time dependence of sodium channel current activation, inactivation, or reactivation.1 Still, SCN5A mutations have been reported in only &20% of patients with Brugada syndrome diagnosed on the basis of clinical criteria, suggesting that other genetic defects and/or other disease mechanisms may give rise to this clinical picture. To complicate matters further, SCN5A mutations have also been identified in patients with the long-QT syndrome. These mutations generally lead to a “gain of function” in the sodium channel, which prolongs the QT interval by increasing inward current. In fact, at least 3 human diseases have been linked to defects in this gene: Brugada syndrome, long-QT syndrome, and progressive conduction disturbances.2–4 Furthermore, there is considerable overlap of clinical profiles, so some patients with Brugada syndrome also have atrial fibrillation, conduction defects with sinus node abnormalities, or prolonged QT interval (reviewed in Reference 1). Thus, genotype-phenotype relationships in Brugada syndrome are highly complex and serve to underscore our incomplete knowledge of the pathogenesis of this type of inherited arrhythmogenic disease. Article p 3680 A similar area of increasing complexity and uncertainty has to …

Trends in thoracic radiology over a decade at a large academic medical center.

To investigate thoracic radiology usage over and above the secular trends associated with hospital-wide changes in the number of patients over a decade. We retrospectively reviewed administrative data from our 905-bed tertiary-care hospital between January 1, 1992, to December 31, 2001. Three points of entry to the radiology department were identified: inpatient (IP), outpatient (OP), and the emergency room (ER). The total numbers of patients, imaging studies, chest radiographs, chest CTs, CTs for pulmonary embolism, pulmonary angiograms, ventilation/perfusion scintigrams (V/Qs), lung biopsies, cardiac and chest MRIs, and FDG-PET scans for lung nodules and masses were collected. The significance of trends using linear regression analysis was evaluated. IP and OP numbers have significantly increased over a decade (P = 0.04 and P = 0.01 respectively); ER patient numbers have not. There has been an increase in the ratio of chest radiographs per patient arising from the ER area (P = 0.0002). All 3 areas demonstrated an increase in the ratio of chest CTs per patient: IP (P = 0.0002), OP (P = <0.0001), and ER (P = <0.0001). IP and ER areas demonstrated an increase in the ratio of CTs for pulmonary embolism per patient (P = 0.006, P = 0.04 respectively). There was a decrease in the ratios of pulmonary angiograms and V/Qs per IP (P = 0.02 & P = 0.0003 respectively). Cardiac MRIs per patient demonstrated an increase (IP P = 0.01, OP P = 0.02). FDG-PET for lung nodules and masses per patient demonstrated an increase in IP (P = 0.03) and OP (P = 0.003) areas. The total number of chest imaging studies divided by the total number of imaging studies demonstrated an increase in IP and ER areas (P = 0.02 and P = 0.02 respectively). There has been an increase in thoracic radiology usage above secular trends, particularly in the regions of chest CT and FDG-PET. CT is replacing more traditional techniques to diagnose pulmonary embolism for inpatients.