Real-time 3D color Doppler allows direct measurement of VC area and may be more accurate for assessment of MR than the conventional VC diameter measurement by 2D color Doppler.

Using a circulatory loop with an incorporated imaging chamber, various pulsatile flow rates of MR were driven through 4 differently sized orifices. In a clinical study of patients with at least mild MR, regurgitation severity was assessed quantitatively using Doppler-derived effective regurgitant orifice area (EROA), and semiquantitatively as recommended by the American Society of Echocardiography. We describe a step-by-step process to accurately identify the 3D-VC area and compare that measure against known orifice areas (in vitro study) and EROA (clinical study).

In vitro, 3D-VC area demonstrated the strongest correlation with known orifice area (r = 0.92, p < 0.001), whereas 2D-VC diameter had a weak correlation with orifice area (r = 0.56, p = 0.01). In a clinical study of 61 patients, 3D-VC area correlated with Doppler-derived EROA (r = 0.85, p < 0.001); the relation was stronger than for 2D-VC diameter (r = 0.67, p < 0.001). The advantage of 3D-VC area over 2D-VC diameter was more pronounced in eccentric jets (r = 0.87, p < 0.001 vs. r = 0.6, p < 0.001, respectively) and in moderate-to-severe or severe MR (r = 0.80, p < 0.001 vs. r = 0.18, p = 0.4, respectively).

Measurement of VC area is feasible with real-time 3D color Doppler and provides a simple parameter that accurately reflects MR severity, particularly in eccentric and clinically significant MR where geometric assumptions may be challenging.

Vortices that form during LV filling have specific geometry and anatomical locations that are critical determinants of directed blood flow during ejection. Therefore, it is clinically relevant to assess the vortex flow patterns to better understand the LV function.

Twenty-five patients (10 normal and 15 patients with abnormal LV systolic function) underwent CE with intravenous contrast agent, Definity (Bristol-Myers Squibb Medical Imaging, Inc., North Billerica, Massachusetts). The velocity vector and vorticity were estimated by particle image velocimetry. Average vortex parameters including vortex depth, transverse position, length, width, and sphericity index were measured. Vortex pulsatility parameters including relative strength, vortex relative strength, and vortex pulsation correlation were also estimated.

Vortex depth and vortex length were significantly lower in the abnormal LV function group (0.443 ± 0.04 vs. 0.482 ± 0.06, p < 0.05; 0.366 ± 0.06 vs. 0.467 ± 0.05, p < 0.01, respectively). Vortex width was greater (0.209 ± 0.05 vs. 0.128 ± 0.06, p < 0.01) and sphericity index was lower (1.86 ± 0.5 vs. 3.66 ± 0.6, p < 0.001) in the abnormal LV function group. Relative strength (1.13 ± 0.4 vs. 2.10 ± 0.8, p < 0.001), vortex relative strength (0.57 ± 0.2 vs. 1.19 ± 0.5, p < 0.001), and vortex pulsation correlation (0.63 ± 0.2 vs. 1.31 ± 0.5, p < 0.001) were significantly lower in the abnormal LV function group.

It was feasible to quantify LV vorticity arrangement by CE using particle image velocimetry in normal subjects and those with LV systolic dysfunction, and the vorticity imaging by CE may serve as a novel approach to depict vortex, the principal quantity to assess the flow structure.

Catecholamine sensitivity is reduced in failing hearts as a result of myocardial abnormalities in the beta-adrenergic receptor signaling pathway. However, little is known about adrenergic myocardial contractile reserve in asymptomatic or mildly symptomatic patients with DCM.

The maximal first derivative of left ventricular pressure (LV dP/dt_max) was determined during infusion of dobutamine (10 µg kg^–1 min^–1) in 46 asymptomatic or mildly symptomatic (New York Heart Association functional class I or II) patients with DCM. The expression of messenger ribonucleic acid (mRNA) for contractile regulatory proteins in endomyocardial biopsy specimens was quantified by reverse transcription and real-time polymerase chain reaction analysis. Plasma norepinephrine levels were measured in all patients and [¹²³I]metaiodobenzylguanidine (MIBG) scintigraphy performed.

Patients were classified into 3 groups based on the percentage increase in LV dP/dt_max induced by dobutamine (LV dP/dt_max) and on LV ejection fraction (LVEF) at baseline: group I (n = 18): LV dP/dt_max >100% and LVEF >25%; group IIa (n = 17): LV dP/dt_max ≤100% and LVEF > 25%; and group IIb (n = 11): LV dP/dt_max ≤100% and LVEF ≤25%. The amounts of beta₁-adrenergic receptor, sarcoplasmic reticulum Ca²⁺-adenosine triphosphatase, and phospholamban mRNA were significantly smaller in groups IIa and IIb than in group I. The plasma norepinephrine level was increased and the delayed heart/mediastinum count ratio in MIBG scintigraphy was decreased in both groups IIa and IIb.

Dobutamine stress testing is a useful diagnostic tool for identifying reduced adrenergic myocardial contractile reserve related to altered myocardial expression of beta₁-adrenergic receptor, sarcoplasmic reticulum Ca²⁺-adenosine triphosphatase, and phospholamban genes even in asymptomatic or mildly symptomatic patients with DCM.

The CS–GCV has become an anatomical structure of interest because it provides a way of access to the heart for a number of interventional procedures. Previous reports demonstrate that the postulated close anatomical proximity of the CS–GCV to the MVA does not always hold true in patients, both in autopsy specimens and in vivo by computed tomography.

In 31 participants (24 volunteers and 7 patients; 15 men; 42 ± 19 years), cardiovascular magnetic resonance was performed for noninvasive evaluation of the coronary sinus and of the coronary arteries using whole-heart imaging and intravascular contrast agents. Three-dimensional reconstructions, standard orthogonal planes, and unprocessed raw data were used to assess CS–GCV anatomy and its relation to the MVA and the LCX along their entire course.

The CS–GCV was located behind the left atrium in all examined participants, at a minimum distance of 8.6 ± 3.9 mm from the MVA. In 80% of the participants, the LCX crossed the CS–GCV inferiorly, between the CS–GCV and the MVA. The CS–GCV and the LCX had a parallel course for 26.2 ± 23.0 mm, with great variability of location and length. In several participants, the CS–GCV had a long parallel course, but in other participants, the LCX crossed below the CS–GCV at a discrete point.

In all participants, the CS–GCV coursed behind the left atrium rather than behind the MVA. In the majority of the participants, the LCX coursed between the CS–GCV and the MVA. These anatomical relationships should be kept in mind when referring a patient for interventional procedures requiring the access to the CS–GCV, and cardiovascular magnetic resonance might provide important information for the selection of candidates for these procedures.

Although it is generally thought that the aorta becomes tortuous with aging, there has been no systematic study to date in healthy adults to determine if this is so. Such age-related aortic elongation may be a confounding factor for the PWV measurement in elderly people.

Arterial lengths were computed by the 3-dimensional transverse magnetic resonance image arterial tracing of the aorta and carotid and iliac arteries in 256 apparently healthy adults (age 19 to 79 years).

The ascending aorta was greater with advancing age (r = 0.72), whereas the lengths of the descending aorta and carotid and iliac arteries were not associated with age. The elongation of the ascending aorta was associated with the corresponding increases in aortic PWV (beta = 0.50) and brachial/aortic pulse pressure ratio (beta = 0.24), which is an index of pulse wave amplification. The straight distance between carotid and femoral sites (car-fem), the most popular arterial length measurement, overestimated the aortic length measured with the magnetic resonance image by ~25%. The most accurate arterial length estimation was the distance obtained by subtracting carotid length from the car-fem, with <5% difference from the magnetic resonance image-measured length. Because the ascending aorta was omitted or subtracted from the length estimation in PWV, the impact of age-related elongation of the aorta on PWV was small.

The aorta lengthens with age, even in healthy humans, due primarily to the elongation of the ascending aorta. Age-related aortic elongation has little impact on PWV measurements, as the ascending aorta, which undergoes lengthening with age, is not included in the arterial length measurements.

Intracoronary optical coherence tomography (OCT) is a catheter-based optical imaging modality that is capable of providing microscopic (~7-µm axial resolution, ~30-µm transverse resolution), cross-sectional images of the coronary wall. Although the use of OCT has shown substantial promise for imaging coronary microstructure, blood attenuates the OCT signal, necessitating prolonged, proximal occlusion to screen long arterial segments. OFDI is a second-generation form of OCT that is capable of acquiring images at much higher frame rates. The increased speed of OFDI enables rapid, 3-dimensional imaging of long coronary segments after a brief, nonocclusive saline purge.

Volumetric OFDI images were obtained in 3 patients after intracoronary stent deployment. Imaging was performed in the left anterior descending and right coronary arteries with the use of a nonocclusive saline purge rates ranging from 3 to 4 ml/s and for purge durations of 3 to 4 s. After imaging, the OFDI datasets were segmented using previously documented criteria and volume rendered.

Good visualization of the artery wall was obtained in all cases, with clear viewing lengths ranging from 3.0 to 7.0 cm at pullback rates ranging from 5 to 20 mm/s. A diverse range of microscopic features were identified in 2 and 3 dimensions, including thin-capped fibroatheromas, calcium, macrophages, cholesterol crystals, bare stent struts, and stents with neointimal hyperplasia. There were no complications of the OFDI procedure.

Our results demonstrate that OFDI is a viable method for imaging the microstructure of long coronary segments in patients. Given its ability to provide microscopic information in a practical manner, this technology may be useful for studying human coronary pathophysiology in vivo and as a clinical tool for guiding the management of coronary artery disease.

Nesiritide, a recombinant human B-type natriuretic peptide is approved for the treatment of acute decompensated HF and has been shown to exert favorable hemodynamic, neurohormonal, and symptomatic effects. The renal effect of nesiritide in HF patients has not been well defined.

In 15 patients with acute decompensated HF, intravascular Doppler and quantitative angiography of the renal artery were used to assess the effect of nesiritide on renal artery diameter and velocity time integral as well as renal blood flow and vascular resistance. Nesiritide was administered intravenously at a standard dose of 2 µg/kg bolus followed by a continuous infusion at a rate of 0.01 µg/kg/min. Assessment of nesiritide effect was made at 15 min.

Nesiritide infusion was associated with a significant central hemodynamic effect including a fall in mean pulmonary artery pressure (36 ± 12 mm Hg to 31 ± 13 mm Hg, p < 0.001), mean pulmonary capillary wedge pressure (21 ± 2 mm Hg to 15 ± 10 mm Hg, p < 0.001), and systemic vascular resistance (1,995 ± 532 dynes·s·cm^–5 to 1,563 ± 504 dynes·s·cm^–5, r < 0.001), and an increase in cardiac output from 3.9 ± 1.2 l/min to 4.6 ± 1.6 l/min (p = 0.001). Nesiritide was also associated with a significant vasodilatory effect on the large conductance renal arteries resulting in an increase in renal artery diameter from 6.2 ± 0.7 mm to 6.7 ± 0.8 mm (p < 0.001). At the same time, there was a concomitant fall in mean renal artery pressure (99 ± 17 mm Hg to 89 ± 13 mm Hg, p = 0.002) and renal blood flow velocity time integral (27 ± 15 cm/beat to 23 ± 15 cm/beat, p = 0.008) and, therefore, no significant change in renal blood flow or renal vascular resistance.

The nesiritide effect on the renal circulation in patients with HF is complex, with a marked vasodilatory action on the large, conductance renal arteries but a concomitant fall in velocity time integral and no effect on renal vascular resistance or renal blood flow. Lack of increase in renal blood flow may be due to a fall in renal blood pressure or an intrarenal vasoconstrictive effect.

The degree of mechanical dyssynchrony has been suggested as a predictor of response to cardiac resynchronization therapy. There have been no published reports of dyssynchrony assessment with the use of CT.

Thirty-eight subjects underwent electrocardiogram-gated contrast-enhanced 64-slice multidetector CT. The left ventricular endocardial and epicardial boundaries were delineated from short-axis images reconstructed at 10% phase increments of the cardiac cycle. Global and segmental CT dyssynchrony metrics that used changes in wall thickness, wall motion, and volume over time were assessed for reproducibility. We defined a global metric using changes in wall thickness as the dyssynchrony index (DI).

The DI was the most reproducible metric (interobserver and intraobserver intraclass correlation coefficients ≥0.94, p < 0.0001) and was used to determine differences between the 3 groups: HF-wide QRS group (ejection fraction [EF] 22 ± 8%, QRS 163 ± 28 ms), HF-narrow QRS (EF 26 ± 7%, QRS 96 ± 11 ms), and age-matched control subjects (EF 64 ± 5%, QRS 87 ± 9 ms). Mean DI was significantly different between the 3 groups (HF-wide QRS: 152 ± 44 ms, HF-narrow QRS: 121 ± 58 ms, and control subjects: 65 ± 12 ms; p < 0.0001) and greater in the HF-wide QRS (p < 0.0001) and HF-narrow QRS (p = 0.005) groups compared with control subjects. We found that DI had a good correlation with 2-dimensional (r = 0.65, p = 0.012) and 3-dimensional (r = 0.68, p = 0.008) echocardiographic dyssynchrony.

Quantitative assessment of global CT-derived DI, based on changes in wall thickness over time, is highly reproducible and renders significant differences between subjects most likely to have dyssynchrony and age-matched control subjects.

Multidetector computed tomography (MDCT) permits study of cardiac chamber size, function, and mass. Age- and gender-specific mean values are not available.

A total of 103 normotensive, nonobese adults (43% women, age 51 ± 14 years) who presented consecutively to 2 medical centers for clinically indicated MDCTs with neither history of nor MDCT evidence of significant cardiovascular disease were studied for left ventricular (LV) and right ventricular (RV) end-systolic (ES) and end-diastolic (ED) linear dimensions and volumes; LV and RV ejection fraction (EF), and LV mass (LVM); and left atrial (LA) and right atrial (RA) end-systolic volumes (LAESV and RAESV, respectively) by 1-dimensional (1D), 2-dimensional (2D), and 3-dimensional (3D) measurements.

The LV volumes using 3D techniques were lower than 2D techniques (LVEDV mean 144 ± 71 ml vs. 150 ± 70 ml), with higher LVEF (63 ± 15% vs. 57 ± 13%) (p < 0.001 for both). Mean LVM/height^2.7 was 24.3 ± 11.0 g/m^2.7 and mean relative wall thickness was 0.16 to 0.44. Evaluation by 20 versus 10 cardiac phases resulted in higher LVEF (mean difference: 3.4 ± 9.0%, p < 0.001). For LVEDV, interobserver (r = 0.99, p < 0.001) and intraobserver (r² = 0.97, p < 0.001) correlations were high. Mean RVEDV was 82 ± 57 ml and RVEF was 58 ± 16. The LAESV determined by 3D techniques was higher than by that determined by 2D methods (102 ± 48 ml vs. 87 ± 57 ml, p = 0.0003). The RAESV determined by 3D techniques was 111.9 ± 29.1 ml. The LV size and LVM were greater in men than in women (p < 0.01). The LV size declined with age (p < 0.01), but LVM did not.

This study establishes age- and gender-specific values for LV, RV, LA, and RA size, function, and mass in adults free of cardiovascular disease, hypertension, and obesity using 1D, 2D, and 3D methods. These data can be used as a reference for future MDCT studies.

There remains a significant nonresponse rate to CRT. MR-MT provides high quality mechanical activation data throughout the heart, and delayed enhancement cardiac magnetic resonance (DE-CMR) offers precise characterization of myocardial scar.

MR-MT was performed in 2 cohorts of heart failure patients with: 1) a CRT heart failure cohort (n = 20; left ventricular ejection fraction of 0.23 ± 0.057) to evaluate the role of MR-MT and DE-CMR prior to CRT; and 2) a multimodality cohort (n = 27; ejection fraction of 0.20 ± 0.066) to compare MR-MT and tissue Doppler imaging septal-lateral delay for assessment of mechanical dyssynchrony. MR-MT was also performed in 9 healthy control subjects.

MR-MT showed that control subjects had highly synchronous contraction (CURE 0.96 ± 0.01), but tissue Doppler imaging indicated dyssynchrony in 44%. Using a cutoff of <0.75 for CURE based on receiver-operator characteristic analysis (area under the curve: 0.889), 56% of patients tested positive for mechanical dyssynchrony, and the MR-MT CURE predicted improved function class with 90% accuracy (positive and predictive values: 87%, 100%); adding DE-CMR (% total scar <15%) data improved accuracy further to 95% (positive and negative predictive values: 93%, 100%). The correlation between CURE and QRS duration was modest in all cardiomyopathy subjects (r = 0.58, p < 0.001). The multimodality cohort showed a 30% discordance rate between CURE and tissue Doppler imaging septal-lateral delay.

The MR-MT assessment of circumferential mechanical dyssynchrony predicts improvement in function class after CRT. The addition of scar imaging by DE-CMR further improves this predictive value.

In thalassemia syndromes, there is an important clinical need to risk stratify patients for the development of iron-overload cardiomyopathy so that chelation therapy can be adjusted and cardiac morbidity averted. This purpose may be served by measuring the magnetic resonance imaging (MRI)-derived parameter T2*, which varies inversely with tissue iron concentration but has limited availability. As diastolic dysfunction may precede systolic dysfunction, we sought to directly compare more readily available echocardiographic indices of diastolic function to myocardial T2* and ejection fraction (EF).

We identified 47 paired echocardiography and MRI examinations in 24 patients with TDT. Echocardiographic measurements of transmitral flow velocities (E, A), tissue Doppler velocities (E'), and left ventricular volume and EF were compared with MRI measurements of myocardial T2*, ventricular volume, and EF.

All patients had a restrictive filling pattern (E/A ≥1.5 and deceleration time <140 ms) and normal relaxation. There was no significant correlation between E/E' or the Tei index versus EF. Although E/A and E' had statistically significant correlations with EF, the relationships were weak with all correlation coefficients <0.52. The parameters E/A, E', E/E', and the Tei index did not significantly correlate with myocardial iron concentration as assessed by MRI T2*. Increased myocardial iron as measured by T2* was strongly associated with lower left ventricular EF, with a T2* <9 ms having a sensitivity of 100% and specificity of 89% for MRI EF <50%.

In patients with TDT, echocardiographic diastolic function parameters correlated poorly with EF and myocardial T2* and were thus not well-suited for risk stratification. Myocardial T2* had a strong relationship with EF and appears to be a promising approach for predicting the development of heart failure and for iron chelator dose adjustment.

The LV hypertrophy and alterations in LV geometry are associated with an increased risk of adverse cardiovascular events.

Quantitative echocardiographic analyses were performed at baseline in 603 patients from the VALIANT (VALsartan In Acute myocardial iNfarcTion) echocardiographic study. The left ventricular mass index (LVMi) and relative wall thickness (RWT) were calculated. Patients were classified into 4 mutually exclusive groups based on RWT and LVMi as follows: normal geometry (normal LVMi and normal RWT), concentric remodeling (normal LVMi and increased RWT), eccentric hypertrophy (increased LVMi and normal RWT), and concentric hypertrophy (increased LVMi and increased RWT). Cox proportional hazards models were used to evaluate the relationships among LVMi, RWT, LV geometry, and clinical outcomes.

Mean LVMi and RWT were 98.8 ± 28.4 g/m² and 0.38 ± 0.08. The risk of death or the composite end point of death from cardiovascular causes, reinfarction, heart failure, stroke, or resuscitation after cardiac arrest was lowest for patients with normal geometry, and increased with concentric remodeling (hazard ratio [HR]: 3.0; 95% confidence interval [CI]: 1.9 to 4.9), eccentric hypertrophy (HR: 3.1; 95% CI: 1.9 to 4.8), and concentric hypertrophy (HR: 5.4; 95% CI: 3.4 to 8.5), after adjusting for baseline covariates. Also, baseline LVMi and RWT were associated with increased mortality and nonfatal cardiovascular outcomes (HR: 1.22 per 10 g/m² increase in LVMi; 95% CI: 1.20 to 1.30; p < 0.001) (HR: 1.60 per 0.1-U increase in RWT; 95% CI: 1.30 to 1.90; p < 0.001). Increased risk associated with RWT was independent of LVMi.

Increased baseline LV mass and abnormal LV geometry portend an increased risk for morbidity and mortality following high-risk myocardial infarction. Concentric LV hypertrophy carries the greatest risk of adverse cardiovascular events including death. Higher RWT was associated with an increased risk of cardiovascular complications after high-risk myocardial infarction.

Congestive heart failure (CHF) is a leading cause for hospitalization and, once hospitalized, patients with CHF frequently are readmitted. To date, no reliable index exists that can be used to predict whether patients with ADHF can be discharged with low readmission likelihood.

A total of 75 patients who were admitted with a primary diagnosis of ADHF were followed. All patients were assessed at admission and discharge with the use of routine clinical evaluation, BNP measurement, and HCU evaluation of the IVC by physicians with limited training in ultrasound.

During the 30-day follow-up, 31 patients were rehospitalized or presented to the emergency department. Patients who were subsequently readmitted could not be differentiated from those who were not readmitted by their demographics, comorbidities, vital signs, presence of symptoms/signs suggestive of persistent congestion, hospital length of stay, or net volume removal. Routine laboratory tests, including assessment of renal function, also failed to predict readmission with the exception of serum sodium. Although admission BNP was similar in patients readmitted and not readmitted, pre-discharge log-transformed BNP was greater in patients who subsequently were readmitted. Patients who required repeat hospitalization had a larger IVC size on admission as well as at discharge. In addition, patients who were readmitted had persistently plethoric IVCs with lower IVC collapsibility indexes. At discharge, only serum sodium, log-transformed BNP, IVC size, and collapsibility were statistically significant predictors of readmission.

This study confirms that, once hospitalized, patients with CHF frequently are readmitted. Bedside evaluation of the IVC with a HCU device at the time of admission and discharge, as well as pre-discharge BNP, identified patients admitted with ADHF who were more likely to be readmitted to the hospital.

The image evaluation of VT has been limited by the lack of technical tools and its often-dramatic hemodynamic effect. Objective bedside imaging of VT-induced changes in contraction pattern, synchrony, and volumes has never been performed but could aid in the understanding of rhythm tolerance.

Equilibrium radionuclide angiography (ERNA) with phase analysis was performed during the course of 32 VT rhythms. Left ventricular ejection fraction, wall motion, synchrony, relative volumes, and exit sites were compared in 13 patients tolerant to VT (Group I) and 9 intolerant to VT (Group II).

The ERNA VT exit site agreed with the results of electrocardiogram in 26 of 32 (81%) cases and with electrophysiologic study in 16 of 19 (84%) cases (both p < 0.05). A greater rate (157 vs. 130, p < 0.0001) accompanied VT intolerance, but the exit site in 4 patients with multiple VT patterns also appeared important to tolerance. Left ventricular ejection fraction, similar in both groups in sinus rhythm, decreased with VT in Groups I (28 to 19) and II (31 to 15), both p<0.03, with a greater relative decrease in LV ejection fraction, LV stroke volume (65% vs. 45%, p < 0.01), cardiac output (30% vs. 2%), and LV end-diastolic volume (36% vs. 27%, both p < 0.001), in Group II. The standard deviation of LV phase angle (Ø) was the only parameter which differed between Groups I and II (35 vs. 45, p < 0.01) in sinus rhythm. With VT, wall motion deteriorated generally, but with greater standard deviation LVØ, p < 0.05, and dyssynchrony in Group II. Ventricular tachycardia induced 14 functional aneurysms, often adjacent to VT exit sites.

A challenging bedside imaging protocol evaluated VT-induced changes. We found that the use of ERNA demonstrated function, synchrony, and volume differences between tolerant and intolerant VT rhythms, delineated the contraction pattern, and localized exit sites.

Mitral annular calcification is common in the elderly and is associated with atherosclerotic risk factors. Its impact on the risk of cardiovascular events is controversial.

The study cohort consisted of 1,955 subjects, ages ≥40 years, and free of prior myocardial infarction (MI) and ischemic stroke (IS). Mitral annular calcification was assessed by transthoracic 2-dimensional echocardiography. The association between MAC and MI, IS, and vascular death (VD) was examined by Cox proportional hazard models with adjustment for established cardiovascular risk factors. The effect of MAC thickness was also analyzed.

The mean age of the cohort was 68.0 ± 9.7 years and the majority of subjects were Hispanics (56.8%). A total of 519 subjects (26.6%) had MAC. Of 498 patients with MAC thickness measurements available, 253 (13.1%) had mild to moderate MAC (1 to 4 mm) and 245 (12.7%) severe MAC (>4 mm). During a mean follow-up of 7.4 ± 2.5 years, MI occurred in 100 (5.1%) subjects, IS in 104 (5.3%) subjects, and VD in 155 (8.0%) subjects. After adjustment for other cardiovascular risk factors, MAC was associated with an increased risk of MI (adjusted hazard ratio [HR]: 1.75; 95% confidence interval [CI]: 1.13 to 2.69, p = 0.011) and VD (adjusted HR: 1.53; 95% CI: 1.09 to 2.15, p = 0.015), but not IS (adjusted HR: 1.34; 95% CI: 0.87 to 2.05, p = 0.18). Further analysis revealed that the impact of MAC was related to its thickness, with MAC >4 mm being a strong and independent predictor of MI (adjusted HR: 1.89; 95% CI: 1.13 to 3.17, p = 0.008) and VD (adjusted HR: 1.81; 95% CI: 1.21 to 2.72, p = 0.002), and showing borderline association with IS (adjusted HR: 1.59; 95% CI: 0.95 to 2.67, p = 0.084).

In this multiethnic cohort, MAC was a strong and independent predictor of cardiovascular events, especially MI and VD. The risk increase was directly related to MAC severity.

Antiangiogenesis therapy may normalize atherosclerotic plaque vasculature and promote plaque stabilization. β₃-targeted paramagnetic nanoparticles can quantify atherosclerotic angiogenesis and incorporate fumagillin to elicit acute antiangiogenic effects.

In the first experiment, hyperlipidemic rabbits received β₃-targeted fumagillin nanoparticles (0, 30, or 90 µg/kg) with either a continued high fat diet or conversion to standard chow. The antiangiogenic response was followed for 4 weeks by cardiac magnetic resonance (CMR) molecular imaging with β₃-targeted paramagnetic nanoparticles. In a second 8-week study, atherosclerotic rabbits received atorvastatin (0 or 44 mg/kg diet) alone or with β₃-targeted fumagillin nanoparticles (only week 0 vs. weeks 0 and 4), and angiogenesis was monitored with CMR molecular imaging. Histology was performed to determine the location of bound nanoparticles and to correlate the level of CMR enhancement with the density of angiogenic vessels.

The β₃-targeted fumagillin nanoparticles reduced the neovascular signal by 50% to 75% at 1 week and maintained this effect for 3 weeks regardless of diet and drug dose. In the second study, atherosclerotic rabbits receiving statin alone had no antineovascular benefit over 8 weeks. The β₃-targeted fumagillin nanoparticles decreased aortic angiogenesis for 3 weeks as in study 1, and readministration on week 4 reproduced the 3-week antineovascular response with no carry-over benefit. However, atorvastatin and 2 doses of β₃-targeted fumagillin nanoparticles (0 and 4 weeks) achieved marked and sustainable antiangiogenesis. Microscopic studies corroborated the high correlation between CMR signal and neovessel counts and confirmed that the β₃-targeted nanoparticles were constrained to the vasculature of the aortic adventia.

The CMR molecular imaging with β₃-targeted paramagnetic nanoparticles demonstrated that the acute antiangiogenic effects of β₃-targeted fumagillin nanoparticles could be prolonged when combined with atorvastatin, representing a potential strategy to evaluate antiangiogenic treatment and plaque stability.

Lipid core plaques cannot be detected by conventional tests, yet are suspected to be the cause of most acute coronary syndromes. Near-infrared spectroscopy is widely used to determine the chemical content of substances. A NIRS system has been developed and used successfully in 99 patients.

Scanning NIRS was performed through blood in 212 coronary segments from 84 autopsy hearts. One histologic section was analyzed for every 2 mm of artery. Lipid core plaque of interest (LCP) was defined as a lipid core >60° in circumferential extent, >200-µm thick, with a mean fibrous cap thickness <450 µm. The first 33 hearts were used to develop the algorithm; the subsequent 51 validation hearts were used in a prospective, double-blind manner to evaluate the accuracy of NIRS in detecting LCP. A NIRS-derived lipid core burden index for an entire artery was also validated by comparison to histologic findings.

The LCPs were present in 115 of 2,649 (4.3%) sections from the 51 validation hearts. The algorithm prospectively identified LCP with a receiver-operator characteristic area of 0.80 (95% confidence interval [CI]: 0.76 to 0.85). The lipid core burden index detected the presence or absence of any fibroatheroma with an area under the curve of 0.86 (95% CI: 0.81 to 0.91). A retrospective analysis of lipid core burden index conducted in extreme artery segments with either no or extensive fibroatheroma yielded an area under the curve of 0.96 (95% CI: 0.92 to 1.00), confirming the accuracy of spectroscopy in identifying plaques with markedly different lipid content under ideal circumstances.

This novel catheter-based NIRS system accurately identified lipid core plaques through blood in a prospective study in coronary autopsy specimens. It is expected that this novel capability will be of assistance in the management of patients with coronary artery disease.

Reproducibility and accuracy of RT3DE evaluation of LV volumes has not been validated in multicenter studies, and LV volumes have been reported to be underestimated compared to cardiac magnetic resonance (CMR) standard.

A total of 92 patients with a wide range of ejection fractions underwent CMR and RT3DE imaging at 4 different institutions. Images were analyzed to obtain LV end-systolic volume (ESV) and end-diastolic volume (EDV). Reproducibility was assessed using repeated analyses. The investigation of potential sources of error included: phantom imaging, intermodality analysis-related differences, and differences in LV boundary identification, such as inclusion of endocardial trabeculae and mitral valve plane in the LV volume.

The RT3DE-derived LV volumes correlated highly with CMR values (EDV: r = 0.91; ESV: r = 0.93), but were 26% and 29% lower consistently across institutions, with the magnitude of the bias being inversely related to the level of experience. The RT3DE measurements were less reproducible (4% to 13%) than CMR measurements (4% to 7%). Minimal changes in endocardial surface position (1 mm) resulted in significant differences in measured volumes (11%). Exclusion of trabeculae and mitral valve plane from the CMR reference eliminated the intermodality bias.

The RT3DE-derived LV volumes are underestimated in most patients because RT3DE imaging cannot differentiate between the myocardium and trabeculae. To minimize this difference, tracing the endocardium to include trabeculae in the LV cavity is recommended. With the understanding of these intermodality differences, RT3DE quantification of LV volume is a reliable tool that provides clinically useful information.

Myocardial metabolism abnormalities may contribute to the development of obesity-related heart failure. Increased myocardial oxygen consumption (MVO₂) and fatty acid (FA) metabolism and decreased efficiency occur with obesity in women. It is unknown whether similar changes occur with obesity in men.

We quantified cardiac work, efficiency, myocardial blood flow (MBF), MVO₂, glucose, and FA metabolism with echocardiography and positron emission tomography in nonobese and obese men and women (N = 86).

There were significant differences between the obese (n = 35) and nonobese (n = 51) subjects in age, body composition, plasma lipids, and insulin resistance in addition to differences between the men (n = 30) and women (n = 56) in body composition and plasma lipids. Female gender independently predicted increased cardiac work (p < 0.001). Female gender also related to lower efficiency (p < 0.05). Obesity and female gender independently predicted greater MBF (p < 0.01, p < 0.0005, respectively) and MVO₂ (p < 0.0005, p < 0.0001). Myocardial glucose uptake was not different among the 4 subject groups, but obesity and gender interacted in predicting glucose uptake (p < 0.05). Lower myocardial glucose utilization was independently predicted by female gender (p < 0.05), and it independently predicted lower myocardial glucose utilization/plasma insulin (p < 0.05). Obesity and gender significantly interacted in the determination of glucose utilization/plasma insulin (p = 0.01). There were no differences in FA uptake among the 4 groups, and although increasing obesity correlated with greater myocardial FA utilization and oxidation; female gender (p < 0.005, p < 0.01) and plasma triglycerides (p < 0.05, p < 0.005) were their independent predictors.

Women's and men's myocardial metabolic responses to obesity are not exactly the same. Obesity and gender modulate MBF and MVO₂, are related to myocardial substrate metabolism, and sometimes interact in its prediction. Gender modifies efficiency. Gender-related differences in myocardial metabolism may affect the development of/adaptation to obesity-related cardiac disease.

A combined perfusion and infarction CMR examination can accurately diagnose CAD in the clinical setting in a mixed gender population.

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.

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).

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.

The prevalence and distribution of LGE and its relationship to left ventricular mass (LVM) and function in this population is unknown.

Chronic hemodialysis patients at high risk for cardiovascular events—age >50 years, diabetes, or known cardiovascular disease—were enrolled prior to concerns regarding nephrogenic systemic fibrosis. Cardiovascular magnetic resonance imaging was performed in 24 patients (age, 59 ± 11 years; dialysis, 45 ± 38 months) and included steady-state free precession cine imaging and late gadolinium-enhanced, phase-sensitive, inversion-recovery gradient echo images. Left ventricular mass, volumes, and function were calculated and indexed to body surface area. A 16-segment analysis was performed to calculate percentage of LGE, LV wall thickness, and percentage of wall thickening.

Left ventricular ejection fraction was 48 ± 15%, and the LV mass index was 100 ± 52 g/m². Late gadolinium enhancement was observed in 79% (19 of 24) of patients in 3 distinct patterns: infarct-related (32%, 6 of 19), diffuse (37%, 7 of 19), and focal noninfarct (37%, 7 of 19). Late gadolinium enhancement constituted 15 ± 18% of the LVM and correlated with LVM (r = 0.44, p = 0.03). A significant, inverse relationship existed between segmental LGE and the percentage of wall thickening (p > 0.0001). Excluding infarct-related segments, as end-diastolic wall thickness increased, so did LGE (p < 0.0001), and as LGE increased, the percentage of wall thickening decreased (p = 0.0012). After 23 ± 3 months of follow-up, 1 patient had developed nephrogenic systemic fibrosis. Seven of the patients (29%) had developed a hard cardiovascular event, 5 of 19 (26%) with LGE and 2 of 5 (40%) without.

Late gadolinium enhancement is prevalent in the hemodialysis population and its extent is related to LVM. Most cases of LGE are not infarct-related and are associated with hypertrophied, dysfunctional LV segments. Non-infarct-related LGE may signify fibrosis from LV hypertrophy and/or an infiltrative process. Further studies in this patient population will not be possible due to the risk of nephrogenic systemic fibrosis.

The binary approach used to assess coronary stenoses on CCTA does not adequately describe borderline obstructive lesions and limits full expression of clinically useful information.

From 84 patients who underwent CCTA and invasive angiography, we identified 278 native coronary segments with ≥25% stenosis on CCTA after excluding all <25% stenotic, stented, and uninterpretable segments. Fifty <25% stenotic segments were randomly selected as controls. Segmental stenosis severity on CCTA was consensually graded using a 0 to 5 scale (grade 0 = none, grade 1 = 1% to 24%, grade 2 = 25% to 49%, grade 3 = 50% to 69%, grade 4 = 70% to 89%, grade 5 = 90% to 100%) by 2 readers, using visual inspection and computed tomography–based quantification (CTQCA). Invasive angiography–based stenosis quantification (IQCA) was performed for all segments, using the same 0 to 5 scale to score stenosis severity.

On CCTA, 185 (56%) segments had intermediate stenoses (grade 2 or grade 3). Stenosis severity by IQCA increased significantly with each step-up in CCTA grade (p < 0.001). CTQCA did not perform better than visual inspection. Visual CCTA stenosis grading differed from IQCA by >1 grade in only 4% of grade 2 to grade 5 segments (10 of 278; 2% of CCTA grade 2 segments, 4% of grade 3, 8% of grade 4, 2% of grade 5). Overall quantitative correlation was strong (r = 0.82) with high variability in agreement between CTQCA and IQCA for individual segments (95% of differences between 27.2% and 34.6%).

With current CCTA technology, experienced readers should consider adopting a visually based, multitiered grading approach to evaluate coronary stenoses. A ≤49% lesion on CCTA can be considered virtually exclusive of ≥70% stenosis by invasive angiography.

The lesion morphologies before and after coronary stenting have been proposed as important predictors of clinical outcome. The high resolution of OCT provides detailed information of coronary vessel wall.

We enrolled 55 patients (UAP: n = 24, SAP: n = 31), and examined lesion morphologies by using OCT at pre- and post-SES implantation and 9 months' follow-up.

The incidence of plaque rupture (42% vs. 3%, p < 0.001), intracoronary thrombus (67% vs. 3%, p ≤ 0.001) and thin-capped fibroatheroma (cap thickness <65 µm; 46% vs. 3%, p < 0.001) at pre-intervention was significantly greater in UAP than that in SAP. Although stent profiles and procedural characteristics were not different between the 2 groups, inadequate stent apposition (67% vs. 32%, p = 0.038) and tissue protrusion (79% vs. 42%, p = 0.005) after percutaneous coronary intervention were observed more frequently in patients with UAP. Plaque rupture was significantly increased after percutaneous coronary intervention in patients with UAP (42% to 75%, p = 0.018), and the persistence of core cavity after plaque rupture (28% vs. 4%, p = 0.031) at 9 months' follow-up was observed more frequently in UAP patients compared with SAP patients. At 9 months' follow-up, the incidence of inadequately apposed stent (33% vs. 4%, p = 0.012) and partially uncovered stent by neointima (72% vs. 37%, p = 0.019) was significantly greater in UAP patients than that in SAP patients. All patients took aspirin and ticlopidine during follow-up period, and no patients had stent thrombosis or adverse coronary events.

Serial OCT examinations demonstrated markedly different vascular response up to 9 months after SES implantation between UAP and SAP patients. Although the inadequate lesion morphologies after stenting were observed more frequently in UAP patients, these findings were not associated with adverse outcomes in patients with antiplatelet therapy.

The imaging characteristics of PP in patients with acute myocardial infarction are not well known.

Intravascular ultrasound (IVUS) imaging was performed in 310 patients immediately following stenting for their first acute myocardial infarction. Multiple clinical, angiographic and IVUS derived variables were compared among patients with and without intrastent PP.

The PP was detected in 27% of the 310 lesions examined. Stent length was longer (31 ± 13 mm vs. 21 ± 8 mm, p < 0.001), and positive remodeling (48% vs. 32%, p = 0.008), plaque rupture (51% vs. 31%, p = 0.001), and thrombus (40% vs. 21%, p = 0.001) were significantly more common in PP lesions compared with non-PP lesions. The creatine kinase-myocardial band (CK-MB) was significantly greater after stenting in PP lesions compared with non-PP lesions ( = +12.3 ± 32.0 U/l vs. –4.9 ± 46.1 U/l, p = 0.002). During a 1-month follow-up, the incidence of stent thrombosis was not significantly different between PP and non-PP lesions [2/85 (2.4%) vs. 2/225 (0.9%), p = 0.308]. Multivariate analysis showed that PP (odds ratio [OR]: 7.34, p < 0.001), plaque rupture (OR: 1.95, p = 0.023), and thrombus (OR: 1.84, p = 0.026) were independently associated with post-stenting CK-MB elevation, and stent length (OR: 2.39, p = 0.003), plaque rupture (OR: 1.96, p = 0.015), and positive remodeling (OR: 1.72, p = 0.044) were independently associated with the development of PP.

PP occurs in one-fourth of infarct-related arteries after stent implantation. Lesion characteristics such as plaque rupture and positive remodeling, together with longer stent predict PP. Although long-term follow-up is pending, PP is associated with more myonecrosis after stenting in patients with acute myocardial infarction.

A noninvasive test to monitor the efficacy of therapy inducing angiogenesis is needed. The interaction between extracellular matrix and endothelial cells in sprouting capillaries is effected primarily by vβ3 integrins that bind through RGD motifs.

At 21 ± 4 days, after left circumflex coronary artery ameroid constrictor placement, 8 swine received endomyocardial injection of 1.2 mg phVEGF₁₆₅ divided into 6 sites and 6 swine received saline (S) using nonfluoroscopic 3-dimensional endocardial mapping system (Noga)-guided delivery. After 20 ± 6 days, 13 animals were injected with 6.4 ± 1.7 mCi [¹²³I]Gluco-RGD, 1 VEGF (vascular endothelial growth factor)-injected animal with I-123–labeled peptide control, and all animals with 2.5 ± 0.4 mCi of Tl-201 and underwent single-photon emission computed tomography imaging. Blood flow and echocardiographic measurements were made at both time points and tissue analyzed for fibrosis and capillary density by lectin staining.

Hibernating myocardium in the ameroid constrictor territory at time of injections was documented by reduced wall thickening compared with remote. Ratio of myocardial blood flow in left circumflex coronary artery/left anterior descending coronary artery territories increased by 15 ± 11% in the VEGF animals and fell 13 ± 12% in S-injected (p < 0.01). There was a small increase in wall thickening in constrictor territory after VEGF (8 ± 17%) while in S-injected animals wall thickening fell by 23 ± 31% (p = 0.01 vs. VEGF). Lectin staining as percent positive tissue staining for ameroid territory was higher in VEGF-injected compared with S-injected animals (2.5 ± 1.5% vs. 0.87 ± 0.52%, p = 0.01). Focal uptake of [¹²³I]Gluco-RGD corresponding to Tl-201 defects was seen in VEGF-injected but not in S-injected animals. [¹²³I]Gluco-RGD uptake in the ameroid territory as percent injected dose correlated with lectin staining (R² = 0.80, p = 0.002).

These data suggest that single-photon emission computed tomography imaging of radiolabeled RGD peptides may be a useful noninvasive method to monitor therapy that induces angiogenesis in the heart.