Myocardial strain imaging using echocardiography can be a cost-effective method to objectively quantify ventricular wall motion but few studies have compared strain measured with echocardiography against MRI in small animals.
Methods and Results
We compared circumferential (CS) and radial strain (RS) measured with echocardiography (vector velocity imaging [VVI]) to displacement encoding with stimulated-echo (DENSE) MRI in two mouse models of cardiomyopathy. In 3 month old mice with gene targeted deficiency of cardiac myosin binding protein-C (cMyBP-C−/−, n=6) or muscle LIM protein (MLP−/−, n=6), and wild-type (WT) mice (n=8), myocardial strains were measured at three cross-sectional levels and averaged to obtain global strains. There was modest correlation between VVI and MRI measured strains, with global CS yielding stronger correlation compared to global RS (CS R2 = 0.4452 vs. RS R2 = 0.2794, both p<0.05). Overall, strain measured by VVI was more variable than MRI (p<0.05) and the limits of agreement were slightly, but not significantly (p=0.14) closer for global CS than RS. Both VVI and MRI strain measurements showed significantly lower global CS strain in the knockout groups compared to the wild-type. The VVI (but not MRI) CS strain measurements were different between the two knockout groups (−14.5 ± 3.8% vs. −6.6 ± 4.0%, cMyBP-C−/− vs. MLP−/− respectively, p<0.05).
Measurements of LV circumferential and radial strains are feasible in small animals using 2D echocardiography. VVI and MRI strain measurements correlated modestly and the agreement between the modalities tended to be greater for circumferential than radial strain. Although VVI and MRI strains were able to differentiate between wild-type and knockout mice, only global circumferential VVI strain differentiated between the two models of cardiomyopathy.
strain; speckle-tracking echocardiography; magnetic resonance imaging
Peripheral arterial disease; Computed tomographic angiography; Magnetic resonance angiography; Duplex ultrasonography
Pulmonary hypertension (PH) has diverse causes with heterogeneous physiology compelling distinct management. Differentiating patients with primarily elevated pulmonary vascular resistance (PVR) from those with PH predominantly due to elevated left sided filling pressure is critical.
Methods and Results
We reviewed hemodynamics, echocardiography, and clinical data for 108 patients seen at a referral PH clinic with transthoracic echocardiogram and right heart catheterization within 1 year. We derived a simple echocardiographic prediction rule to allow hemodynamic differentiation of PH due to pulmonary vascular disease (PHPVD, defined as pulmonary artery wedge pressure (PAWP) ≤ 15mmHg and PVR >3WU). Age averaged 61.3±14.8 years, μPAWP and PVR were 16.4±7.1mmHg and 6.3±4.0WU respectively, and 52 (48.1%) patients fulfilled PHPVD hemodynamic criteria. The derived prediction rule ranged from −2 to +2 with higher scores suggesting higher probability of PHPVD: +1 point for left atrial AP dimension<3.2cm; +1 for presence of a mid-systolic notch or acceleration time<80msec; −1 for lateral mitral E:e′>10; −1 for left atrial AP dimension>4.2cm. PVR increased stepwise with score (for −2, 0 and +2, μPVR were 2.5, 4.5, and 8.1WU) while the inverse was true for PAWP (corresponding μPAWP were 21.5, 16.5 and 10.4mmHg). Among subjects with complete data, the score had an AUC of 0.921 for PHPVD. A score ≥ 0 had 100% sensitivity and 69.3% positive predictive value for PHPVD, with 62.3% specificity. No patients with a negative score had PHPVD. Patients with a negative score and acceleration time >100msec had normal PVR (μPVR=1.8WU, range=0.7–3.2WU).
We present a simple echocardiographic prediction rule that accurately defines PH hemodynamics facilitates improved screening and focused clinical investigation for PH diagnosis and management.
pulmonary heart disease; echocardiography; heart failure; hemodynamics
Whole-heart coronary MR angiography (MRA) is a promising method for non-invasive, radiation-free detection and exclusion of obstructive coronary artery disease (CAD); however, the required imaging time and robustness of the technique are not yet satisfactory. We evaluated the value of whole-heart coronary MRA at 3.0T using a 32-channal cardiac coil, which reduces image acquisition times and hence allows to increase the clinical throughput.
Methods and Results
A total of 110 consecutive patients with suspected CAD referred for clinically indicated conventional coronary angiography were included in this prospective study. 32-channel receiver coils were used for 3.0T coronary MRA data acquisition. An ECG-triggered, navigator-gated, inversion-recovery prepared, segmented gradient-echo sequence was used for image acquisition with an acceleration factor of three in the phase-encoding direction using GRAPPA reconstruction. Acquisition of coronary MRA was successfully completed in 101 of 110 (92%) patients with average imaging time of 7.0 ± 1.8 min. The sensitivity, specificity, positive and negative predictive value of coronary MRA on a patient-based analysis were 95.9% (47/49, 95% CI: 86.0% to 99.4%), 86.5% (45/52, 95% CI, 74.2% to 94.4%), 87.0% (47/54, 95% CI, 75.1% to 94.6%) and 95.7% (45/47, 95% CI, 85.4% to 99.4%), respectively.
Whole-heart coronary MRA at 3.0 T using a 32-channal cardiac coil allows high overall accuracy for detecting significant CAD with reduced imaging time. It has potential to be a robust and alternative technique for ruling out significant CAD.
Clinical Trial Registration
URL: http://www.chictr.org. Unique identifier: ChiCTR-DDT-07000121.
magnetic resonance angiography; coronary arteries; 3.0 T
Interventions to increase brown adipose tissue (BAT) volume and activation are being extensively investigated as therapies to decrease the body weight in obese subjects. Noninvasive methods to monitor these therapies in animal models and humans are rare. We investigated whether contrast ultrasound (CU) performed in mice could detect BAT and measure its activation by monitoring BAT blood flow. After validation, CU was used to study the role of uncoupling protein 1 (UCP1) and nitric oxide synthases in the acute regulation of BAT blood flow.
Methods and Results
Blood flow of interscapular BAT was assessed in mice (n=64) with CU by measuring the signal intensity of continuously infused contrast microbubbles. Blood flow of BAT estimated by CU was 0.5±0.1 (mean±SEM) dB/s at baseline and increased 15-fold during BAT stimulation by norepinephrine (NE, 1 μg·kg−1·min−1). Assessment of BAT blood flow using CU was correlated to that performed with fluorescent microspheres (R2=0.86, p<0.001). To evaluate whether intact BAT activation is required to increase BAT blood flow, CU was performed in UCP1-deficient (UCP1−/−) mice with impaired BAT activation. Norepinephrine infusion induced a smaller increase in BAT blood flow in UCP1−/− mice than in wild-type mice. Finally, we investigated whether NOS played a role in acute NE-induced changes of BAT blood flow. Genetic and pharmacologic inhibition of NOS3 attenuated the NE-induced increase in BAT blood flow.
These results indicate that CU can detect BAT in mice, and estimate BAT blood flow in mice with functional differences in BAT.
brown adipose tissue; imaging; contrast ultrasound; uncoupling protein; nitric oxide synthase
Patients with repaired tetralogy of Fallot (TOF) are monitored for pulmonary regurgitation (PR), and right ventricular (RV) function. We sought to compare measures of PR and RV function on echocardiogram to those on cardiac magnetic resonance (CMR), and to develop a new tool for assessing PR by echocardiogram.
Methods and Results
Patients with repaired TOF (N=143, 12.5± 3.2 years) had an echocardiogram and CMR within three months of each other. On echocardiogram, RV function was assessed by (1) Doppler tissue imaging of the RV free wall, and (2) myocardial performance index (MPI). The ratio of diastolic and systolic time-velocity integrals (DSTVI) measured by Doppler of the main pulmonary artery was calculated. CMR variables included RV ejection fraction (EF), RV volumes, and pulmonary regurgitant fraction (RF). Pulmonary regurgitation was graded as mild (RF <20%), moderate (RF=20–40%), and severe (RF>40%). On CMR, RF was 34±17% and RV EF was 61±8%. Echocardiography had good sensitivity identifying cases with RF>20% (sensitivity 97%, 95% CI: 92–99%) but overestimated the amount of PR when RF<20% (false positive rate 36%, 95% CI: 18–57%). The DSTVI on echocardiogram showed moderate correlation with RF on CMR (R=0.60, P<0.0001). On CMR, RF of 20% and 40% corresponded with a DSTVI of 0.49 (95% CI: 0.44–0.56), and 0.72 (95% CI: 0.68–0.76), respectively. RV MPI correlated modestly with RV EF (r=−0.33, P<0.001).
This study suggests that the DSTVI ratio may make a modest contribution to the overall assessment of PR in patients with repaired TOF and warrants further investigation. However, echocardiography continues to have a limited ability to quantify PR and RV function as compared to CMR.
echocardiography; regurgitation; tetralogy of Fallot
MRI; molecular imaging; myocardial infarction; inflammation; iron oxide nanoparticles
Because cancer patients survive longer, the impact of cardiotoxicity associated with the use of cancer treatments escalates. The present study investigates whether early alterations of myocardial strain and blood biomarkers predict incident cardiotoxicity in patients with breast cancer during treatment with anthracyclines, taxanes, and trastuzumab.
Methods and Results
Eighty-one women with newly diagnosed human epidermal growth factor receptor 2–positive breast cancer, treated with anthracyclines followed by taxanes and trastuzumab were enrolled to be evaluated every 3 months during their cancer therapy (total of 15 months) using echocardiograms and blood samples. Left ventricular ejection fraction, peak systolic longitudinal, radial, and circumferential myocardial strain were calculated. Ultrasensitive troponin I, N-terminal pro–B-type natriuretic peptide, and the interleukin family member (ST2) were also measured. Left ventricular ejection fraction decreased (64 ± 5% to 59 ± 6%; P<0.0001) over 15 months. Twenty-six patients (32%, [22%–43%]) developed cardiotoxicity as defined by the Cardiac Review and Evaluation Committee Reviewing Trastuzumab; of these patients, 5 (6%, [2%–14%]) had symptoms of heart failure. Peak systolic longitudinal myocardial strain and ultrasensitive troponin I measured at the completion of anthracyclines treatment predicted the subsequent development of cardiotoxicity; no significant associations were observed for left ventricular ejection fraction, N-terminal pro–B-type natriuretic peptide, and ST2. Longitudinal strain was <19% in all patients who later developed heart failure.
In patients with breast cancer treated with anthracyclines, taxanes, and trastuzumab, systolic longitudinal myocardial strain and ultrasensitive troponin I measured at the completion of anthracyclines therapy are useful in the prediction of subsequent cardiotoxicity and may help guide treatment to avoid cardiac side-effects.
chemotherapy; echocardiography; biomarkers; left ventricular function; heart failure; trastuzumab
Aging is accompanied by an alteration in myocardial contractility. However, its noninvasive detection is difficult. The effect of chronic exercise on this decrease is unknown. Murine models of senescence are increasingly used to test therapies in aging. We tested whether strain rate imaging detected left ventricular (LV) systolic dysfunction in aging mice and was able to assess a potential improvement after exercise.
Methods and Results
Young (3 weeks), adult (2 to 3 months), and old (6 to 18 months) C57BL6 male mice underwent echocardiograms with strain rate imaging, either in sedentary conditions or before, 2 weeks and 4 weeks after chronic swimming. Hemodynamic parameters of LV function including maximal and end-systolic elastance were obtained before euthanizing. LV fibrosis was measured using Sirius red staining. Conventional echocardiography was unable to detect LV systolic dysfunction in old mice, whereas both systolic strain rate and load-independent hemodynamic parameters such as preload recruitable stroke work and end-systolic elastance were significantly decreased. Both strain rate and load-independent hemodynamic parameters normalized after 4 weeks of exercise. Both endocardial and epicardial fibrosis were increased in the LV of aging mice. Endocardial fibrosis decreased in exercised aged mice.
Strain rate noninvasively detects LV systolic dysfunction associated with aging in mice, whereas conventional echocardiography does not. Chronic exercise normalizes LV systolic function and decreases fibrosis in old mice. Strain rate imaging in mice may be a useful tool to monitor the effect of new therapeutic strategies preventing the myocardial dysfunction associated with aging.
aging; echocardiography; exercise
There are ongoing efforts to optimize patient selection criteria for cardiac resynchronization therapy (CRT). In this regard, the relationship between acute change in left ventricular synchrony (LV) after CRT and patient outcome remains undefined.
Methods and Results
A novel protocol was designed to evaluate acute change in left LV synchrony after CRT using phase analysis of standard gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging with a single injection of radiotracer and prospectively applied to 44 patients undergoing CRT. Immediately after CRT, 18 (41%), 11 (25%), and 15 (34%) patients had an improvement, no change, or a worsening in LV synchrony. An algorithm incorporating the presence of baseline dyssynchrony, myocardial scar burden, and lead concordance predicted acute improvement or no change in LV synchrony with 72% sensitivity, 93% specificity, 96% positive predictive value, and 64% negative predictive value and had 96% negative predictive value for acute deterioration in synchrony. Over a follow-up period of 9.6±6.8 months, patients who had an acute deterioration in synchrony after CRT had a higher composite event rate of death, heart failure hospitalizations, appropriate defibrillator discharges, and CRT device deactivation for worsening heart failure symptoms, compared with patients who had an improvement or no change [hazard ratio, 4.6 (1.3 to 16.0); log rank test; P=0.003].
In this single-center pilot study, phase analysis of gated SPECT was successfully used to predict acute change in LV synchrony and patient outcome after CRT.
cardiac resynchronization therapy; dyssynchrony; phase analysis; single-photon emission computed tomography
Human cardiac progenitor cells have demonstrated great potential for myocardial repair in small and large animals, but robust methods for longitudinal assessment of their engraftment in humans is not yet readily available. In this study, we sought to optimize and evaluate the use of positron emission tomography (PET) reporter gene imaging for monitoring human cardiac progenitor cell (hCPC) transplantation in a mouse model of myocardial infarction.
Methods & Results
hCPCs were isolated and expanded from human myocardial samples and stably transduced with variations of the thymidine kinase (TK) PET reporter gene. TK-expressing hCPCs were characterized in vitro and transplanted into murine myocardial infarction models (n=60). Cardiac echocardiographic, magnetic resonance imaging (MRI), and pressure-volume (PV) loop analyses revealed improvement in left ventricular contractile function two weeks after transplant (hCPC vs. PBS, P<0.03). Noninvasive PET imaging was used to track hCPC fate over a four week time period, demonstrating a substantial decline in surviving cells. Importantly, early cell engraftment as assessed by PET was found to predict subsequent functional improvement, implying a “dose-effect” relationship. We isolated the transplanted cells from recipient myocardium by laser capture microdissection for in vivo transcriptome analysis. Our results provide direct evidence that hCPCs augment cardiac function after their transplantation into ischemic myocardium through paracrine secretion of growth factors.
PET reporter gene imaging can provide important diagnostic and prognostic information regarding the ultimate success of human cardiac progenitor cell treatment for myocardial infarction.
cell therapy; stem cells; imaging; positron emission tomography
Alterations at the level of the coronary circulation with aging may play an important role in the evolution of age-associated changes in left ventricular (LV) fibrosis and function. However these age-associated changes in the coronary vasculature remain poorly defined primarily due to the lack of high resolution imaging technologies. The current study was designed to utilize cardiac micro-computed tomography (micro-CT) technology as a novel imaging strategy, to define the three dimensional coronary circulation in the young and aged heart and its relationship to LV fibrosis and function.
Method and Results
Young (2 month old; n=10) and aged (20 month old; n=10) Fischer rats underwent cardiac micro-CT imaging as well as echocardiography, blood pressure and fibrosis analysis. Importantly when indexed to LV mass which increased with age, the total and intramyocardial vessel volumes were lower, while the epicardial vessel volume, with and without indexing to LV mass, was significantly higher in the aged hearts compared to the young hearts. Moreover the aged hearts had a significantly lower percentage of intramyocardial vessel volume and a significantly higher percentage of epicardial vessel volume, when normalized to the total vessel volume, compared to the young hearts. Further, the aged hearts had significant LV fibrosis and mild LV dysfunction compared to the young hearts.
This micro-CT imaging study reports the reduction in normalized intramyocardial vessel volume within the aged heart, in association with increased epicardial vessel volume, in the setting of increased LV fibrosis and mild LV dysfunction.
computed tomography; aging; coronary vasculature; fibrosis
Increased left ventricular myocardial thickness (LVMT) is a feature of several cardiac diseases. The purpose of this study was to establish standard reference values of normal LVMT with cardiac MR (CMR) and to assess variation with image acquisition plane, demographics and LV function.
Methods and Results
End-diastolic LVMT was measured on CMR steady-state free precession cine long and short axis images in 300 consecutive participants free of cardiac disease (169 women; 65.6±8.5 years) of the Multi-Ethnic Study of Atherosclerosis cohort. Mean LVMT on short axis images at the mid-cavity level was 5.3±0.9mm and 6.3±1.1mm for women and men, respectively. The average of the maximum LVMT at the mid-cavity for women/men were 7mm/9mm (long axis) and 7mm/8mm (short axis). Mean LVMT was positively associated with weight (0.02mm/kg, p=0.01) and body-surface-area (1.1mm/m2, p<0.001). No relationship was found between mean LVMT and age or height. Greater mean LVMT was associated with lower LV end-diastolic volume (0.01mm/ml, p<0.01), a lower LV end-systolic volume (−0.01mm/ml, p=0.01) and lower LV stroke volume (−0.01mm/ml, p<0.05). LVMT measured on long axis images at the basal and mid-cavity level were slightly greater (by 6% and 10%, respectively) than measurements obtained on short axis images; apical LVMT values on long axis images were 20% less than those on short axis images.
Normal values for wall thickness are provided for middle-aged and older subjects. Normal LVMT is lower for women than men. Observed values vary depending on the imaging plane for measurement.
magnetic resonance imaging; myocardial thickness; normal values
Coronary endothelial function (endoFx) is abnormal in patients with established coronary artery disease (CAD) and was recently shown by MRI to relate to the severity of luminal stenosis. Recent advances in MRI now allow the non-invasive assessment of both anatomic and functional (endoFx) changes that previously required invasive studies. We tested the hypothesis that abnormal coronary endoFx is related to measures of early atherosclerosis such as increased coronary wall thickness (CWT).
Methods and Results
Seventeen arteries in fourteen healthy adults and seventeen arteries in fourteen patients with non-obstructive CAD were studied. To measure endoFx, coronary MRI was performed before and during isometric handgrip exercise, an endothelial-dependent stressor and changes in coronary cross-sectional area (CSA) and flow were measured. Black blood imaging was performed to quantify CWT and other indices of arterial remodeling. The mean stress-induced change in CSA was significantly higher in healthy adults (13.5%±12.8%, mean±SD, n=17) than in those with mildly diseased arteries (-2.2±6.8%, p<0.0001, n=17). Mean CWT was lower in healthy subjects (0.9±0.2mm) than in CAD patients (1.4±0.3mm, p<0.0001). In contrast to healthy subjects, stress-induced changes in CSA, a measure of coronary endoFx, correlated inversely with CWT in CAD patients (r= -0.73, p=0.0008).
There is an inverse relationship between coronary endothelial function and local CWT in CAD patients but not in healthy adults. These findings demonstrate that local endothelial-dependent functional changes are related to the extent of early anatomic atherosclerosis in mildly diseased arteries. This combined MRI approach enables the anatomic and functional investigation of early coronary disease.
coronary disease; endothelium; magnetic resonance imaging
The incremental value of regional left ventricular function (LVF) over coronary assessment to detect acute coronary syndrome (ACS) is uncertain.
Methods and Results
We analyzed 356 patients (mean age 53±12 years, 62% male) with acute chest pain and inconclusive initial ED evaluation. Patients underwent 64-slice contrast-enhanced cardiac CT prior to hospital admission. Caregivers and patients remained blinded to the results. Regional LVF and presence of coronary atherosclerotic plaque and significant stenosis (>50%) were separately assessed by two independent readers. Incremental value of regional LVF to predict ACS was determined in the entire cohort and in subgroups of patients with nonobstructive CAD, inconclusive assessment for stenosis (defined as inability to exclude significant stenosis due to calcium or motion), and significant stenosis. During their index hospitalization, 31 patients were ultimately diagnosed with ACS (8 myocardial infarction, 22 unstable angina), of which 74% (23 patients) had regional LV dysfunction. Adding regional LVF resulted in a 10% increase in sensitivity to detect ACS by cardiac CT (87%, 95%-confidence interval [CI]: 70–96%) and significantly improved the overall accuracy (c-statistic: 0.88 vs. 0.94 and 0.79 vs. 0.88, for extent of plaque and presence of stenosis; respectively; both p<0.03). The diagnostic accuracy of regional LVF for detection of ACS has 89% sensitivity and 86% specificity in patients with significant stenosis (n=33) and 60% sensitivity and 86% specificity in patients with inconclusive coronary CTA (n=33).
Regional LVF assessment at rest improves diagnostic accuracy for ACS in patients with acute chest pain, especially in those with coronary artery disease and thus may be helpful to guide further management in patients at intermediate risk for ACS.
Clinical Trial Registration
URL: http://clinicaltrials.gov/ct2/show/NCT00990262. Unique Identifier: NCT00990262
computed tomography; left ventricular function; acute coronary syndrome; emergency department
CMR typically quantifies LV mass (LVM) via manual planimetry (MP), but this approach is time consuming and does not account for partial voxel components - myocardium admixed with blood in a single voxel. Automated segmentation (AS) can account for partial voxels, but this has not been used for LVM quantification. This study used automated CMR segmentation to test the influence of partial voxels on quantification of LVM.
Methods and Results
LVM was quantified by AS and MP in 126 consecutive patients and 10 laboratory animals undergoing CMR. AS yielded both partial voxel (ASPV) and full voxel (ASFV) measurements. Methods were independently compared to LVM quantified on echocardiography (echo) and an ex-vivo standard of LVM at necropsy. AS quantified LVM in all patients, yielding a 12-fold decrease in processing time vs. MP (0:21±0:04 vs. 4:18±1:02 min; p<0.001). ASFV mass (136±35gm) was slightly lower than MP (139±35; Δ=3±9gm, p<0.001). Both methods yielded similar proportions of patients with LV remodeling (p=0.73) and hypertrophy (p=1.00). Regarding partial voxel segmentation, ASPV yielded higher LVM (159±38gm) than MP (Δ=20±10gm) and ASFV (Δ=23±6gm, both p<0.001), corresponding to relative increases of 14% and 17%. In multivariable analysis, magnitude of difference between ASPV and ASFV correlated with larger voxel size (partial r=0.37, p<0.001) even after controlling for LV chamber volume (r=.28, p=0.002) and total LVM (r=0.19, p=0.03). Among patients, ASPV yielded better agreement with echo (Δ=20±25gm) than did ASFV (Δ=43±24gm) or MP (Δ=40±22gm, both p<0.001). Among laboratory animals, ASPV and ex-vivo results were similar (Δ=1±3gm, p=0.3), whereas ASFV (6±3gm, p<0.001) and MP (4±5gm, p=0.02) yielded small but significant differences with LVM at necropsy.
Automated segmentation of myocardial partial voxels yields a 14-17% increase in LVM vs. full voxel segmentation, with increased differences correlated with lower spatial resolution. Partial voxel segmentation yields improved CMR agreement with echo and necropsy-verified LVM.
left ventricular mass; cardiovascular magnetic resonance; echocardiography
imaging; aorta; aneurysm
A high degree of non-compacted (trabeculated) myocardium in relationship to compact myocardium (T/M ratio >2.3) has been associated with a diagnosis of left ventricular non-compaction (LVNC). The purpose of this study was to determine the normal range of the T/M ratio in a large population-based study and to examine the relationship to demographic and clinical parameters.
Methods and Results
The thickness of trabeculation and the compact myocardium were measured in eight LV regions on long axis cardiac magnetic resonance (CMR) steady-state free precession cine images in 1000 participants (551 women; 68.1±8.9 years) of the Multi-Ethnic Study of Atherosclerosis cohort. Of 323 participants without cardiac disease or hypertension and with all regions evaluable 140 (43%) had a T/M ratio >2.3 in at least one region; in 20/323 (6%), T/M>2.3 was present in more than two regions. Multivariable linear regression model revealed no association of age, gender, ethnicity, height and weight with maximum T/M ratio in participants without cardiac disease or hypertension (p>0.05). In the entire cohort (n=1000) LVEF (β=−0.02/%; p=0.015), LVEDV (β=0.01/ml; p=<0.0001) and LVESV (β=0.01/ml; p<0.001) were associated with maximum T/M ratio in adjusted models while there was no association with hypertension or myocardial infarction (p>0.05). At the apical level T/M ratios were significantly lower when obtained on short- compared to long-axis images (p=0.017).
A ratio of trabeculated to compact myocardium of more than 2.3 is common in a large population based cohort. These results suggest reevaluation of the current CMR criteria for LVNC may be necessary.
cardiovascular magnetic resonance imaging; cardiomyopathy; non-compaction; trabeculation
Patients with human immunodeficiency virus (HIV) infection are at increased risk of accelerated coronary artery disease (CAD) and cardiovascular events. Stress echocardiography (SE) is routinely used for risk stratification and prognosis of patients with known or suspected CAD. The prognostic value of SE in this high-risk group is unknown. The purpose of this study was to evaluate the prognostic value of SE in HIV-infected patients with known or suspected CAD.
Methods and Results
We evaluated 311 patients (age, 52±9 years; 74% men; left ventricular ejection fraction, 54±12%) with history of HIV, undergoing SE (56% dobutamine). Left ventricular wall motion was evaluated on a 16-segment model, 5-point scale. An abnormal SE was defined by a fixed (infarction), biphasic, or new (ischemia) wall motion abnormality on stress. Follow-up for cardiac death and myocardial infarction was obtained. Seventy-nine (26%) patients had an abnormal SE. After 2.9±1.9 years, 17 confirmed myocardial infarction and 14 cardiac deaths occurred. SE risk-stratified patients into normal versus abnormal subgroups (event rate, 0.6% per year versus 11.8% per year; P<0.0001). Both abnormal SE (hazard ratio, 28.2; 95% confidence interval, 6.2 to 128.0; P<0.0001) and the presence of any ischemia on SE (hazard ratio, 3.4; 95% confidence interval, 1.3 to 8.6; P=0.009) were independent predictors of cardiac events. On a forward conditional Cox proportional hazards regression model, SE provided incremental prognostic value over clinical, stress ECG, and resting echocardiographic variables (global χ2 increased from 17.8 to 24.5 to 65 to 109, P<0.05 across all groups).
SE can effectively risk-stratify and prognosticate patients with HIV. The presence of ischemia and scar during SE provides independent and incremental prognostic value over traditional variables. A normal SE response portends a benign prognosis even in this high-risk subset.
HIV; stress echo; prognosis
There is a well-recognized need for a new generation of single photon emission computed tomography (SPECT) perfusion tracers with improved myocardial extraction over a wide flow range. Radiotracers that target complex I of the mitochondrial electron transport chain have been proposed as a new class of myocardial perfusion imaging agents. 7-(Z)-[125I]iodorotenone (125I-ZIROT) has demonstrated superior myocardial extraction and retention characteristics in rats and in isolated perfused rabbit hearts. We sought to fully characterize the biodistribution and myocardial extraction versus flow relationship of 123I-ZIROT in an intact large-animal model.
Methods and Results
The 123I-ZIROT was administered during adenosine A2A agonist-induced hyperemia in 5 anesthetized dogs with critical left anterior descending (LAD) stenoses. When left circumflex (LCx) flow was maximal, 123I-ZIROT and microspheres were coinjected and the dogs were euthanized 5 minutes later. 123I-ZIROT biodistribution was evaluated in 2 additional dogs by in vivo planar imaging. At 123I-ZIROT injection, transmural LAD flow was unchanged from baseline (mean±SEM, 0.90±0.22 versus 0.87±0.11 mL/[min · g]; P=0.92), whereas LCx zone flow increased significantly (mean±SEM, 3.25±0.51 versus 1.00±0.17 mL/[min · g]; P<0.05). Myocardial 123I-ZIROT extraction tracked regional myocardial flow better than either thallium-201 or 99mTc-sestamibi from previous studies using a similar model. Furthermore, the 123I-ZIROT LAD/LCx activity ratios by ex vivo imaging or well counting (mean±SEM, 0.42±0.08 and 0.45±0.1, respectively) only slightly underestimated the LAD/LCx microsphere flow ratio (0.32±0.09).
The ability of 123I-ZIROT to more linearly track blood flow over a wide range makes it a promising new SPECT myocardial perfusion imaging agent with potential for improved coronary artery disease detection and better quantitative estimation of the severity of flow impairment.
coronary artery disease; diagnosis; myocardial perfusion imaging; radioisotope
Systemic-pulmonary collateral (SPC) flow occurs commonly in single ventricle patients after superior cavo-pulmonary connection, with unclear clinical significance. We sought to evaluate the association between SPC flow and acute post-Fontan clinical outcomes using a novel method of quantifying SPC flow by cardiac magnetic resonance (CMR).
Methods and Results
All patients who had SPC flow quantified by CMR prior to Fontan were retrospectively reviewed to assess for acute clinical outcomes after Fontan completion. Forty-four subjects were included who had Fontan completion between May, 2008 and September, 2010. SPC flow prior to Fontan measured 1.5 ± 0.9 L/min/m2, accounting for 31 ± 11% of total aortic flow and 44 ± 15% of total pulmonary venous flow. There was a significant linear association between natural log-transformed duration of hospitalization and SPC flow as a proportion of total aortic (rho=0.31, p=0.04) and total pulmonary venous flow (rho=0.29, p=0.05). After adjustment for Fontan type and presence of a fenestration, absolute SPC flow was significantly associated with hospital duration ≥ 7 days (OR=9.2, p=0.02) and chest tube duration ≥ 10 days (OR=22.7, p=0.009). Similar associations exist for SPC flow as a percentage of total aortic (OR=1.09, p=0.048 for hospitalization ≥ 7 days; OR=1.24, p=0.007 for chest tube duration ≥ 10 days) and total pulmonary venous flow (OR=1.07, p=0.048 for hospitalization ≥ 7 days; OR=1.18, p=0.006 for chest tube duration ≥ 10 days).
Increasing SPC flow before Fontan, as measured by CMR, is associated with increased duration of hospitalization and chest tube following Fontan completion.
aortopulmonary collaterals; cardiac magnetic resonance imaging; Fontan procedure; outcomes; single ventricle
We quantified absolute myocardial blood flow (MBF) using a spin labeling magnetic resonance imaging (SL-MRI) method after transplantation of endothelial cells (ECs) into the infarcted heart. Our aims were to study the temporal changes in MBF in response to EC transplantation, and to compare regional MBF with contractile function (wall motion) and microvascular density.
Methods and Results
We first validated the SL-MRI method with the standard microsphere technique in normal rats. We then induced myocardial infarction (MI) in athymic rats and injected 5-million ECs (human umbilical vein endothelial cells) suspended in Matrigel or Matrigel alone (vehicle) along the border of the blanched infarcted area. At 2-weeks post-MI, MBF averaged over the entire slice (p = 0.038) and in the infarcted region (p = 0.0086) was significantly higher in EC vs. vehicle group; the greater MBF was accompanied by an increase of microvasculature density in the infarcted region (p = 0.0105 vs. vehicle). At 4-weeks post-MI, MBF in the remote region was significantly elevated in EC-treated hearts (p = 0.0277); this was accompanied by increased wall motion in this region assessed by circumferential strains. Intraclass correlation coefficients and Bland-Altman plot revealed a good reproducibility of the SL-MRI method.
Myocardial blood flow in free-breathing rats measured by SL-MRI is validated by the standard color microsphere technique. SL-MRI allows quantification of temporal changes of regional MBF in response to EC treatment. The proof-of-principle study indicates that MBF is a unique and sensitive index to evaluate EC-mediated therapy for the infarcted heart.
myocardial blood flow; spin labeling; magnetic resonance imaging; myocardial infarction; human umbilical vascular endothelial cells; microspheres; left ventricular ejection fraction
An increase in left ventricular mass (LVM) is associated with mortality and cardiovascular morbidity in patients with end-stage renal disease.
Methods and Results
The Frequent Hemodialysis Network (FHN) Daily Trial randomized 245 patients to 12 months of 6 times per week daily in-center hemodialysis or conventional hemodialysis; the FHN Nocturnal Trial randomized 87 patients to 12 months of 6 times per week nocturnal hemodialysis or conventional hemodialysis. The main cardiac secondary outcome was change in LVM. In each trial, we examined whether several pre-defined baseline demographic or clinical factors, as well as change in volume removal, blood pressure or solute clearance influenced the effect of frequent hemodialysis on LVM. In the Daily Trial, frequent hemodialysis resulted in a significant reduction in LVM (13.1(95% CI 5.0 to 21.3) g, p=0.002), LVM index (6.9 (2.4 to 11.3) g/m2, p=0.003) and percent change in geometric mean of LVM (7.0 (1.0 to 12.6)%, p =0.02). Similar trends were noted in the Nocturnal Trial but did not reach statistical significance. In the Daily Trial, a more pronounced effect of frequent hemodialysis on LVM was evident among patients with left ventricular hypertrophy at baseline. Changes in LVM were associated with changes in blood pressure (conventional hemodialysis: R=0.28, P=0.01, daily hemodialysis: R=0.54, P<0.001) and were not significantly associated with changes in other parameters.
Frequent in-center hemodialysis reduces LVM. The benefit of frequent hemodialysis on LVM may be mediated by salutary effects on blood pressure.
Left Ventricular Mass; Frequent Hemodialysis; Daily Hemodialysis; Nocturnal Hemodialysis; Blood Pressure